Judith D. Goldberg

Acquired differences in brain responses among monozygotic twins discordant for restrained eating
Schur E.A.; Kleinhans N.M.; Goldberg J.; Buchwald D.S.; Polivy J.; Del Parigi A.; Maravilla K.R.
2012 ;105(2):560-567, Physiology & behavior
We studied whether self-reported intent to exert cognitive control over eating was associated with differences in brain response to food cues, independent of genetic background. Subjects were ten pairs of identical twins in which one twin was a restrained eater and the co-twin was unrestrained, as classified by the Herman and Polivy Restraint Scale. Before and after ingestion of a milkshake, we used functional magnetic resonance imaging to measure brain response to photographs of objects, 'fattening' food, and 'non-fattening' food. At baseline, restrained eaters had greater activation in the left amygdala and the right thalamus in response to fattening food cues than did their unrestrained co-twins. When restrained eaters drank a milkshake, activation in response to fattening food photographs decreased across multiple brain areas, whereas activation induced by non-fattening food photographs increased. As compared to their unrestrained co-twins, restrained eaters who drank a milkshake had greater decreases in activation by fattening food images in the left amygdala and occipital lobe, and greater increases in activation by non-fattening food images in the medial orbitofrontal cortex. Because of the discordant monozygotic twin study design, the findings provide a rigorous level of support for the hypothesis that adopting an intention to restrain eating alters brain response to food cues. 2011 Elsevier Inc
— id: 145741, year: 2012, vol: 105, page: 560, stat: Journal Article,

Matrix Metalloproteinase-2 Conditions Human Dendritic Cells to Prime Inflammatory T(H)2 Cells via an IL-12- and OX40L-Dependent Pathway
Godefroy, Emmanuelle; Manches, Olivier; Dreno, Brigitte; Hochman, Tsivia; Rolnitzky, Linda; Labarriere, Nathalie; Guilloux, Yannick; Goldberg, Judith; Jotereau, Francine; Bhardwaj, Nina
2011 Mar 8;19(3):333-346, Cancer cell
Matrix metalloproteinase-2 (MMP-2) is a proteolytic enzyme degrading the extracellular matrix and overexpressed by many tumors. Here, we documented the presence of MMP-2-specific CD4(+) T cells in tumor-infiltrating lymphocytes (TILs) from melanoma patients. Strikingly, MMP-2-specific CD4(+) T cells displayed an inflammatory T(H)2 profile, i.e., mainly secreting TNF-alpha, IL-4, and IL-13 and expressing GATA-3. Furthermore, MMP-2-conditioned dendritic cells (DCs) primed naive CD4(+) T cells to differentiate into an inflammatory T(H)2 phenotype through OX40L expression and inhibition of IL-12p70 production. MMP-2 degrades the type I IFN receptor, thereby preventing STAT1 phosphorylation, which is necessary for IL-12p35 production. Active MMP-2, therefore, acts as an endogenous type 2 'conditioner' and may play a role in the observed prevalence of detrimental type 2 responses in melanoma
— id: 127238, year: 2011, vol: 19, page: 333, stat: Journal Article,

Outcomes of coronary artery bypass grafting and reduction annuloplasty for functional ischemic mitral regurgitation: A prospective multicenter study (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve)
Grossi, Eugene A; Woo, Y Joseph; Patel, Nirav; Goldberg, Judith D; Schwartz, Charles F; Subramanian, Valavanur A; Genco, Christopher; Goldman, Scott M; Zenati, Marco A; Wolfe, J Alan; Mishra, Yugal K; Trehan, Naresh
2011 Jan;141(1):91-97, Journal of thoracic & cardiovascular surgery
OBJECTIVE: Functional ischemic mitral regurgitation is a complication of ventricular remodeling; standard therapy is reduction annuloplasty and coronary artery bypass grafting. Unfortunately, outcomes are retrospective and contradictory. We report a multicenter study that documents the outcomes of reduction annuloplasty for functional ischemic mitral regurgitation. METHODS: Twenty-one centers randomized 75 patients to the coronary artery bypass grafting + reduction annuloplasty subgroup that was the control arm of the Randomized Evaluation of a Surgical Treatment for Off-pump Repair of the Mitral Valve trial. Entry criteria included patients requiring revascularization, patients with severe or symptomatic moderate functional ischemic mitral regurgitation, an ejection fraction 25% or greater, a left ventricular end-diastolic dimension 7.0 cm or less, and more than 30 days since acute myocardial infarction. All echocardiograms were independently scored by a core laboratory. Reduction annuloplasty was achieved by device annuloplasty. Two patients underwent immediate intraoperative conversion to a valve replacement because reduction annuloplasty was unable to correct mitral regurgitation; as-treated results are presented. RESULTS: Thirty-day mortality was 4.1% (3/73). Patients received an average of 2.8 bypass grafts. Mean follow-up was 24.6 months. Mitral regurgitation was reduced from 2.6 +/- 0.8 preoperatively to 0.3 +/- 0.6 at 2 years. Freedom from death or valve reoperation was 78% +/- 5% at 2 years. There was significant improvement in ejection fraction and New York Heart Association class with reduction of left ventricular end-diastolic dimension. Cox regression analyses suggested that increasing age (P = .001; hazard ratio, 1.16 per year; 95% confidence interval, 1.06-1.26) and renal disease (P = .018; hazard ratio, 3.48; 95% confidence interval, 1.25-9.72) were associated with decreased survival. CONCLUSIONS: Coronary artery bypass grafting + reduction annuloplasty for functional ischemic mitral regurgitation predictably reduces mitral regurgitation and relieves symptoms. This treatment of moderate to severe mitral regurgitation is associated with improved indices of ventricular function, improved New York Heart Association class, and excellent freedom from recurrent mitral insufficiency. Although long-term prognosis remains guarded, this multicenter study delineates the intermediate-term benefits of such an approach
— id: 116214, year: 2011, vol: 141, page: 91, stat: Journal Article,

Prone Hypofractionated Whole-Breast Radiotherapy Without a Boost to the Tumor Bed: Comparable Toxicity of IMRT Versus a 3D Conformal Technique
Hardee ME; Raza S; Becker SJ; Jozsef G; Lymberis SC; Hochman T; Goldberg JD; Dewyngaert KJ; Formenti SC
2011 Mar 1;82(3):e415-e423, International journal of radiation oncology biology physics
PURPOSE: We report a comparison of the dosimetry and toxicity of three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT) among patients treated in the prone position with the same fractionation and target of the hypofractionation arm of the Canadian/Whelan trial. METHODS AND MATERIALS: An institutional review board-approved protocol identified a consecutive series of early-stage breast cancer patients treated according to the Canadian hypofractionation regimen but in the prone position. Patients underwent IMRT treatment planning and treatment if the insurance carrier approved reimbursement for IMRT; in case of refusal, a 3D-CRT plan was used. A comparison of the dosimetric and toxicity outcomes during the acute, subacute, and long-term follow-up of the two treatment groups is reported. RESULTS: We included 97 consecutive patients with 100 treatment plans in this study (3 patients with bilateral breast cancer); 40 patients were treated with 3D-CRT and 57 with IMRT. IMRT significantly reduced the maximum dose (Dmax median, 109.96% for 3D-CRT vs. 107.28% for IMRT; p < 0.0001, Wilcoxon test) and improved median dose homogeneity (median, 1.15 for 3D-CRT vs. 1.05 for IMRT; p < 0.0001, Wilcoxon test) when compared with 3D-CRT. Acute toxicity consisted primarily of Grade 1 to 2 dermatitis and occurred in 92% of patients. Grade 2 dermatitis occurred in 13% of patients in the 3D-CRT group and 2% in the IMRT group. IMRT moderately decreased rates of acute pruritus (p = 0.03, chi-square test) and Grade 2 to 3 subacute hyperpigmentation (p = 0.01, Fisher exact test). With a minimum of 6 months' follow-up, the treatment was similarly well tolerated in either group, including among women with large breast volumes. CONCLUSION: Hypofractionated breast radiotherapy is well tolerated when treating patients in the prone position, even among those with large breast volumes. Breast IMRT significantly improves dosimetry but yields only a modest but confirmed benefit in terms of toxicities. If a concurrent boost to the tumor bed is not required, a conformal 3D-CRT approach can adequately deliver prone whole-breast hypofractionation radiotherapy
— id: 145492, year: 2011, vol: 82, page: e415, stat: Journal Article,

A Note on Monotonicity Assumptions for Exact Unconditional Tests in Binary Matched-Pairs Designs
Li X; Liu M; Goldberg JD
2011 Dec;67(4):1666-18 L, Biometrics
Summary Exact unconditional tests have been widely applied to test the difference between two probabilities for 2 x 2 matched-pairs binary data with small sample size. In this context, Lloyd (2008, Biometrics 64, 716-723) proposed an E + M p-value, that showed better performance than the existing M p-value and C p-value. However, the analytical calculation of the E + M p-value requires that the Barnard convexity condition be satisfied; this can be challenging to prove theoretically. In this article, by a simple reformulation, we show that a weaker condition, conditional monotonicity, is sufficient to calculate all three p-values (M, C, and E + M) and their corresponding exact sizes. Moreover, this conditional monotonicity condition is applicable to noninferiority tests
— id: 131786, year: 2011, vol: 67, page: 1666, stat: Journal Article,

Impact of population genetic substructure on association studies and risk assessment for melanoma
Lobach I; Belitskaya-Levy I; Goldberg JD; Ostrer H; Berman RS; Pavlick AC; Shapiro RL; Osman I; Manga P
2011 ;29(Suppl):?-? #8521, Journal of clinical oncology
Background: Genetic substructure due to varying allele frequencies between populations can confound association studies. Ancestry informative genetic marker (AIMs) data combined with statistical adjustment can reveal spurious associations and identify population specific risk markers. In melanoma, AIMs may also be risk markers, e.g. pigment genes contribute to melanoma susceptibility and segregate with ancestry. We have thus developed a strategy to adjust for population genetic substructure (PGS) using AIMs, while identifying potentially novel genes associated with melanoma. Methods: 326 melanoma patients and 400 controls of European ancestry from the New York area were studied. Tag SNPs spanning 14 candidate genes and 75 AIMs were genotyped and odds ratios (OR), unadjusted and adjusted for PGS, computed. Results: A PGS model based on all AIMs separated cases and controls, suggesting that some AIMs were associated with melanoma. An algorithm was developed to select AIMs least capable of separating cases and controls to infer PGS and validated using simulations. The resulting model, which was reproduced using 49 additional AIMs, separated Northern (NE) and Southern Europeans (SE) and was used to adjust ORs. Three classes of SNPs were identified 1. Associated before and after PGS correction in both groups (10 SNPs localized to MATP, TYR and ERCC5). 2. Not associated in unadjusted analysis, but significantly associated with melanoma in NEs (6 SNPs localized to XPC, ERCC4, OCA2, ASIP and TYR). 3. Associated with melanoma before but not after adjustment. To determine if AIMs that separate cases and controls can identify novel melanoma genes, we genotyped 16 SNPs localized to 4 genes that house candidate AIMs. Four SNPs at 2 different loci were associated with melanoma (e.g. AIM1: OR=0.35, p=0.01; AIM2: OR=1.77, p=0.03). Conclusions: Our approach demonstrated that ancestry is a significant confounding factor in identifying melanoma susceptibility genes. Melanoma risk markers vary significantly between groups and a DNA based risk assessment model will require adjustment for ancestry. We have also identified potentially novel susceptibility melanoma genes for futher study
— id: 132473, year: 2011, vol: 29, page: ?, stat: Journal Article,

Three-year postoperative ultrasensitive prostate-specific antigen following open radical retropubic prostatectomy is a predictor for delayed biochemical recurrence
Malik, Rena D; Goldberg, Judith D; Hochman, Tsivia; Lepor, Herbert
2011 Sep;60(3):548-553, European urology
BACKGROUND: Prostate-specific antigen (PSA) is the only independent predictor of biochemical recurrence (BCR) following radical prostatectomy (RP) subject to change over time. OBJECTIVE: To determine whether an ultrasensitive PSA measured at 3 yr following RP is a predictor of subsequent BCR. DESIGN, SETTING, AND PARTICIPANTS: There were 1197 consecutive men with clinically localized prostate cancer who underwent an open radical retropubic prostatectomy (ORRP) at a tertiary referral academic medical center. Exclusions included 107 men (8.9%) who developed a PSA level >/=0.2 ng/ml or underwent hormone therapy or radiation therapy (RT) within the first 3 r after surgery, 191 men (16%) who did not undergo a 3-yr ultrasensitive PSA assay, and 98 men (8.2%) who had PSA levels >/=0.1 and <0.2 at 3 yr. The remaining 801 men were stratified into two groups based on their ultrasensitive PSA level at 3 yr postoperatively: group 1, which consisted of patients whose PSA was </=0.04 (n=765), and group 2, which consisted of patients whose PSA was >0.04 and <0.10 (n=36). MEASUREMENTS: Delayed BCR was the primary end point and represented those men in this cohort who developed a PSA level >/=0.2 or underwent salvage RT for a persistently rising PSA level after 3 yr of follow-up. RESULTS AND LIMITATIONS: The 7-yr cumulative BCR-free survival rate for groups 1 and 2 was 0.957 (95% confidence interval [CI], 0.920-0.978) and 0.654 (95% CI, 0.318-0.855), respectively. In multivariable Cox proportional hazards models, ultrasensitive PSA level at 3 yr remained the only significant predictor of delayed BCR (likelihood ratio chi(2) for full model: 27.03; df=1; p < 0.001). A limitation of the study is that no uniform PSA assay was obtained. CONCLUSIONS: Our findings provide compelling evidence that an ultrasensitive PSA at 3 yr following RP provides useful insights into delayed BCR and is a source of reassurance for the overwhelming majority of men being followed for delayed recurrences
— id: 135557, year: 2011, vol: 60, page: 548, stat: Journal Article,

Intravoxel incoherent motion imaging of tumor microenvironment in locally advanced breast cancer
Sigmund, E E; Cho, G Y; Kim, S; Finn, M; Moccaldi, M; Jensen, J H; Sodickson, D K; Goldberg, J D; Formenti, S; Moy, L
2011 May;65(5):1437-1447, Magnetic resonance in medicine
Diffusion-weighted imaging plays important roles in cancer diagnosis, monitoring, and treatment. Although most applications measure restricted diffusion by tumor cellularity, diffusion-weighted imaging is also sensitive to vascularity through the intravoxel incoherent motion effect. Hypervascularity can confound apparent diffusion coefficient measurements in breast cancer. We acquired multiple b-value diffusion-weighted imaging at 3 T in a cohort of breast cancer patients and performed biexponential intravoxel incoherent motion analysis to extract tissue diffusivity (D(t) ), perfusion fraction (f(p) ), and pseudodiffusivity (D(p) ). Results indicated significant differences between normal fibroglandular tissue and malignant lesions in apparent diffusion coefficient mean (+/-standard deviation) values (2.44 +/- 0.30 vs. 1.34 +/- 0.39 mum(2) /msec, P < 0.01) and D(t) (2.36 +/- 0.38 vs. 1.15 +/- 0.35 mum(2) /msec, P < 0.01). Lesion diffusion-weighted imaging signals demonstrated biexponential character in comparison to monoexponential normal tissue. There is some differentiation of lesion subtypes (invasive ductal carcinoma vs. other malignant lesions) with f(p) (10.5 +/- 5.0% vs. 6.9 +/- 2.9%, P = 0.06), but less so with D(t) (1.14 +/- 0.32 mum(2) /msec vs. 1.18 +/- 0.52 mum(2) /msec, P = 0.88) and D(p) (14.9 +/- 11.4 mum(2) /msec vs. 16.1 +/- 5.7 mum(2) /msec, P = 0.75). Comparison of intravoxel incoherent motion biomarkers with contrast enhancement suggests moderate correlations. These results suggest the potential of intravoxel incoherent motion vascular and cellular biomarkers for initial grading, progression monitoring, or treatment assessment of breast tumors. Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc
— id: 131795, year: 2011, vol: 65, page: 1437, stat: Journal Article,

Meta-analysis to assess the appropriate endpoint for slow pathway ablation of atrioventricular nodal reentrant tachycardia
Stern, Joshua D; Rolnitzky, Linda; Goldberg, Judith D; Chinitz, Larry A; Holmes, Douglas S; Bernstein, Neil E; Bernstein, Scott A; Khairy, Paul; Aizer, Anthony
2011 Mar;34(3):269-277, Pacing & clinical electrophysiology
BACKGROUND: There are little data on the appropriate endpoint for slow pathway ablation that balances acceptable procedural times, recurrence rates, and complication rates. This study compared recurrence rates of three commonly utilized endpoints of slow pathway ablation for atrioventricular nodal reentrant tachycardia (AVNRT). METHODS: We performed a meta-analysis of AVNRT slow pathway ablation cohorts by searching electronic databases, the Internet, and conference proceedings. Inclusion criteria were age >18 years, >20 human subjects per study, primary AVNRT ablation, English language publication, and >1 month of follow-up. Data were analyzed with a fixed-effects model using Comprehensive Meta-Analysis software version 2.2.046 (Biostat, Englewood, NJ, USA). RESULTS: We included 10 studies encompassing 1,204 patients with a mean age of 41-53 years. Endpoints were complete slow pathway ablation, residual jump only, and single remaining echo beat. Pooled estimates revealed 28 of 641 patients (4.4%) with complete slow pathway ablation, 13 of 192 patients (6.8%) with a residual jump only, and 24 of 371 patients (6.5%) with one echo had recurrences. With uniform isoproterenol use after ablation, there was no significant difference in recurrence rates among the endpoints. However, when isoproterenol was utilized after ablation only if needed to induce AVNRT before ablation, a significantly higher recurrence rate occurred in patients with a residual jump (P = 0.002), a single echo (P = 0.003), or the combined group of a residual jump and/or one echo (P = 0.001). CONCLUSIONS: Isoproterenol should be used routinely after slow pathway modification, when a residual jump and/or single echo remain
— id: 132603, year: 2011, vol: 34, page: 269, stat: Journal Article,

Impact of socioeconomic status and sociodemographic factors on melanoma presentation among ethnic minorities
Wich, Lindsay G; Ma, Michelle W; Price, Leah S; Sidash, Stanislav; Berman, Russell S; Pavlick, Anna C; Miller, George; Sarpel, Umut; Goldberg, Judith D; Osman, Iman
2011 Jun;36(3):461-468, Journal of community health
Minority melanoma patients have worse survival. In this study, we evaluated the impact of socioeconomic and demographic factors on minority melanoma patients presenting to two different New York City hospitals (one public and one private) managed by the same multidisciplinary team. Sociodemographic and clinicopathologic characteristics were retrieved for melanoma patients presenting to Bellevue Hospital Center (BHC), a public hospital, and the New York University Cancer Institute (NYUCI), a private cancer center. Socioeconomic data was obtained from the United States Census Bureau database. The Kruskal-Wallis and chi-square tests were used to evaluate the associations between race/ethnicity and continuous and categorical variables (e.g. income, stage at presentation), respectively. Minorities comprised 2% (27/1296) of melanoma patients at the NYUCI compared to 42% (50/119) at BHC. Those presenting to the NYUCI were more likely to have a higher median household income (P = 0.05), a higher educational level (P = 0.04), and an earlier stage at presentation (P = 0.02) than those at BHC. NYUCI patients were predominantly covered by commercial insurance (70%), whereas Medicaid (62%) was common among BHC patients. Only 19% of Hispanic patients at BHC chose English as their preferred language. Our data demonstrate that language and health care system factors affect melanoma presentation in minorities
— id: 138281, year: 2011, vol: 36, page: 461, stat: Journal Article,

Preoperative concurrent paclitaxel-radiation in locally advanced breast cancer: pathologic response correlates with five-year overall survival
Adams, Sylvia; Chakravarthy, A Bapsi; Donach, Martin; Spicer, Darcy; Lymberis, Stella; Singh, Baljit; Bauer, Joshua A; Hochman, Tsivia; Goldberg, Judith D; Muggia, Franco; Schneider, Robert J; Pietenpol, Jennifer A; Formenti, Silvia C
2010 Dec;124(3):723-732, Breast cancer research & treatment
We have previously demonstrated high pathologic response rates after neoadjuvant concurrent chemoradiation in patients with locally advanced breast cancer (LABC). We now report disease-free survival (DFS) and overall survival (OS) in the context of pathologic response. 105 LABC patients (White 46%, Non-White 54%) were treated with paclitaxel (30 mg/m(2) intravenously twice a week) for 10-12 weeks. Daily radiotherapy was delivered to breast, axillary, and supraclavicular lymph nodes during weeks 2-7 of paclitaxel treatment, at 1.8 Gy per fraction to a total dose of 45 Gy with a tumor boost of 14 Gy at 2 Gy/fraction. Pathological complete response (pCR) was defined as the absence of invasive cancer in breast and lymph nodes and pathological partial response (pPR) as the persistence of <10 microscopic foci of invasive carcinoma in breast or lymph nodes. Pathologic response (pCR and pPR) after neoadjuvant chemoradiation was achieved in 36/105 patients (34%) and was associated with significantly better DFS and OS. Pathological responders had a lower risk of recurrence or death (HR = 0.35, P = 0.01) and a longer OS (HR = 4.27, P = 0.01) compared with non-responders. Median DFS and OS were 57 and 84 months for non-responders, respectively, and have not yet been reached for responders. Importantly, pathologic response was achieved in 54% of patients with HR negative tumors (26/48). In conclusion, pathologic response to concurrent paclitaxel-radiation translated into superior DFS and OS. Half of the patients with HR negative tumors achieved a pathologic response
— id: 114178, year: 2010, vol: 124, page: 723, stat: Journal Article,

Phase I/II study of single-agent bortezomib for the treatment of patients with myelofibrosis. Clinical and biological effects of proteasome inhibition
Barosi, G; Gattoni, E; Guglielmelli, P; Campanelli, R; Facchetti, F; Fisogni, S; Goldberg, J; Marchioli, R; Hoffman, R; Vannucchi, AM
2010 AUG ;85(8):616-619, American journal of hematology
A phase I/II trial was undertaken to determine maximum tolerated dose (MID), toxicity, clinical efficacy, and biological activity of bortezomib in patients with advanced stage primary or postpolycythemia vera/postessential thrombocythemia myelofibrosis (MF). Bortezomib (0.8, 1.0, or 1.3 mg/m(2)) was administered on days 1, 4, 8, and 11 by intravenous push to patients previously resistant to at least one line of therapy, or with an intermediate/high-risk score of International Working Group (IWG) [1]. Therapy was repeated every 28 days for six cycles. At 1.3 mg/m(2) dose, one of six patients experienced a dose limiting toxicity, and this was determined to be the MTD. Neither remissions nor clinical improvements were recorded in 16 patients treated at this dose level, fulfilling the early stopping rule in the Simon two-stage study design. Major toxicity was on thrombocytopenia. In 9 of 15 patients bortezomib proved that it is able to reduce bone marrow vessel density. However, the agent was associated with worsening of markers of disease activity, such as enhancement of hematopoietic CD34-positive progenitor cell mobilization, WT-1 gene expression in mononuclear cells, and downregulation of CXCR4 expression on CD34-positive cells. Occurrence of both beneficial and detrimental biological effects claims further investigation on the mechanisms of the drug in MF
— id: 111800, year: 2010, vol: 85, page: 616, stat: Journal Article,

The Agent Profile: Sixteen Attributes as a Framework for Risk Determination and Response to Agents of Opportunity in Academic Medical Centers
Farmer, B. M.; Nelson, L. S.; Tunik, M. G.; Graham, M. E.; Bendzans, C.; McCrillis, A.; Portelli, I; Zhang, M.; Goldberg, J. D.; Goldfrank, L. R.
2010 MAR ;48(3):256-256, Clinical Toxicology (Philadelphia)
— id: 139127, year: 2010, vol: 48, page: 256, stat: Journal Article,

Developing a consensus framework and risk profile for agents of opportunity in academic medical centers: implications for public health preparedness
Farmer, Brenna M; Nelson, Lewis S; Graham, Margaret E; Bendzans, Carly; McCrillis, Aileen M; Portelli, Ian; Zhang, Meng; Goldberg, Judith; Rosenberg, Sheldon D; Goldfrank, Lewis R; Tunik, Michael
2010 Dec;4(4):318-325, Disaster medicine & public health preparedness
Agents of opportunity (AO) in academic medical centers (AMC) are defined as unregulated or lightly regulated substances used for medical research or patient care that can be used as 'dual purpose' substances by terrorists to inflict damage upon populations. Most of these agents are used routinely throughout AMC either during research or for general clinical practice. To date, the lack of careful regulations for AOs creates uncertain security conditions and increased malicious potential. Using a consensus-based approach, we collected information and opinions from staff working in an AMC and 4 AMC-affiliated hospitals concerning identification of AO, AO attributes, and AMC risk and preparedness, focusing on AO security and dissemination mechanisms and likely hospital response. The goal was to develop a risk profile and framework for AO in the institution. Agents of opportunity in 4 classes were identified and an AO profile was developed, comprising 16 attributes denoting information critical to preparedness for AO misuse. Agents of opportunity found in AMC present a unique and vital gap in public health preparedness. Findings of this project may provide a foundation for a discussion and consensus efforts to determine a nationally accepted risk profile framework for AO. This foundation may further lead to the implementation of appropriate regulatory policies to improve public health preparedness. Agents of opportunity modeling of dissemination properties should be developed to better predict AO risk
— id: 122674, year: 2010, vol: 4, page: 318, stat: Journal Article,

Agent of opportunity risk mitigation: people, engineering, and security efficacy
Graham, Margaret E; Tunik, Michael G; Farmer, Brenna M; Bendzans, Carly; McCrillis, Aileen M; Nelson, Lewis S; Portelli, Ian; Smith, Silas; Goldberg, Judith D; Zhang, Meng; Rosenberg, Sheldon D; Goldfrank, Lewis R
2010 Dec;4(4):291-299, Disaster medicine & public health preparedness
BACKGROUND: Agents of opportunity (AO) are potentially harmful biological, chemical, radiological, and pharmaceutical substances commonly used for health care delivery and research. AOs are present in all academic medical centers (AMC), creating vulnerability in the health care sector; AO attributes and dissemination methods likely predict risk; and AMCs are inadequately secured against a purposeful AO dissemination, with limited budgets and competing priorities. We explored health care workers' perceptions of AMC security and the impact of those perceptions on AO risk. METHODS: Qualitative methods (survey, interviews, and workshops) were used to collect opinions from staff working in a medical school and 4 AMC-affiliated hospitals concerning AOs and the risk to hospital infrastructure associated with their uncontrolled presence. Secondary to this goal, staff perception concerning security, or opinions about security behaviors of others, were extracted, analyzed, and grouped into themes. RESULTS: We provide a framework for depicting the interaction of staff behavior and access control engineering, including the tendency of staff to 'defeat' inconvenient access controls. In addition, 8 security themes emerged: staff security behavior is a significant source of AO risk; the wide range of opinions about 'open' front-door policies among AMC staff illustrates a disparity of perceptions about the need for security; interviewees expressed profound skepticism concerning the effectiveness of front-door access controls; an AO risk assessment requires reconsideration of the security levels historically assigned to areas such as the loading dock and central distribution sites, where many AOs are delivered and may remain unattended for substantial periods of time; researchers' view of AMC security is influenced by the ongoing debate within the scientific community about the wisdom of engaging in bioterrorism research; there was no agreement about which areas of the AMC should be subject to stronger access controls; security personnel play dual roles of security and customer service, creating the negative perception that neither role is done well; and budget was described as an important factor in explaining the state of security controls. CONCLUSIONS: We determined that AMCs seeking to reduce AO risk should assess their institutionally unique AO risks, understand staff security perceptions, and install access controls that are responsive to the staff's tendency to defeat them. The development of AO attribute fact sheets is desirable for AO risk assessment; new funding and administrative or legislative tools to improve AMC security are required; and security practices and methods that are convenient and effective should be engineered
— id: 116222, year: 2010, vol: 4, page: 291, stat: Journal Article,

Outcomes of the RESTOR-MV Trial (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve)
Grossi, Eugene A; Patel, Nirav; Woo, Y Joseph; Goldberg, Judith D; Schwartz, Charles F; Subramanian, Valavanur; Feldman, Ted; Bourge, Robert; Baumgartner, Norbert; Genco, Christopher; Goldman, Scott; Zenati, Marco; Wolfe, J Alan; Mishra, Yugal K; Trehan, Naresh; Mittal, Sanjay; Shang, Shulian; Mortier, Todd J; Schweich, Cyril J Jr
2010 Dec 7;56(24):1984-1993, Journal of the American College of Cardiology
OBJECTIVES: We sought to determine whether patients with functional mitral regurgitation (FMR) would benefit from ventricular reshaping by the Coapsys device (Myocor, Inc., Maple Grove, Minnesota). BACKGROUND: FMR occurs when ventricular remodeling impairs valve function. Coapsys is a ventricular shape change device placed without cardiopulmonary bypass to reduce FMR. It compresses the mitral annulus and reshapes the ventricle. We hypothesized that Coapsys for FMR would improve clinical outcomes compared with standard therapies. METHODS: RESTOR-MV (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve) was a randomized, prospective, multicenter study of patients with FMR and coronary disease with core laboratory analysis. After enrollment, patients were stratified to the standard indicated surgery: either coronary artery bypass graft alone or coronary artery bypass graft with mitral valve repair. In each stratum, randomization was to either control (indicated surgery) or treatment (coronary artery bypass graft with Coapsys ventricular reshaping). RESULTS: The study was terminated when the sponsor failed to secure ongoing funding; 165 patients were randomized. Control and Coapsys both produced decreases in left ventricular (LV) end-diastolic dimension and MR at 2 years (p < 0.001); Coapsys provided a greater decrease in LV end-diastolic dimension (p = 0.021). Control had lower MR grades during follow-up (p = 0.01). Coapsys showed a survival advantage compared with control at 2 years (87% vs. 77%) (hazard ratio: 0.421; 95% confidence interval: 0.200 to 0.886; stratified log-rank test; p = 0.038). Complication-free survival (including death, stroke, myocardial infarction, and valve reoperation) was significantly greater with Coapsys at 2 years (85% vs. 71%) (hazard ratio: 0.372; 95% confidence interval: 0.185 to 0.749; adjusted log-rank test; p = 0.019). CONCLUSIONS: Analysis of RESTOR-MV indicates that patients with FMR requiring revascularization treated with ventricular reshaping rather than standard surgery had improved survival and a significant decrease in major adverse outcomes. This trial validates the concept of the ventricular reshaping strategy in this subset of patients with heart failure. (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve [RESTOR-MV]; NCT00120276)
— id: 115277, year: 2010, vol: 56, page: 1984, stat: Journal Article,

Endothelin receptor type B gene promoter hypermethylation in salivary rinses is independently associated with risk of oral cavity cancer and premalignancy
Pattani, Kavita Malhotra; Zhang, Zhe; Demokan, Semra; Glazer, Chad; Loyo, Myriam; Goodman, Steven; Sidransky, David; Bermudez, Francisco; Jean-Charles, Germain; McCaffrey, Thomas; Padhya, Tapan; Phelan, Joan; Spivakovsky, Silvia; Bowne, Helen Yoo; Goldberg, Judith D; Rolnitzky, Linda; Robbins, Miriam; Kerr, A Ross; Sirois, David; Califano, Joseph A
2010 Sep;3(9):1093-1103, Cancer prevention research (Philadelphia, Pa.)
Endothelin receptor type B (EDNRB) and kinesin family member 1A (KIF1A) are candidate tumor suppressor genes that are inactivated in cancers. In this study, we evaluated the promoter hypermethylation of EDNRB and KIF1A and their potential use for risk classification in prospectively collected salivary rinses from patients with premalignant/malignant oral cavity lesions. Quantitative methylation-specific PCR was performed to analyze the methylation status of EDNRB and KIF1A in salivary rinses of 191 patients. We proceeded to determine the association of methylation status with histologic diagnosis and estimate classification accuracy. On univariate analysis, diagnosis of dysplasia/cancer was associated with age and KIF1A or EDNRB methylation. Methylation of EDNRB highly correlated with that of KIF1A (P < 0.0001). On multivariable modeling, histologic diagnosis was independently associated with EDNRB (P = 0.0003) or KIF1A (P = 0.027) methylation. A subset of patients analyzed (n = 161) without prior biopsy-proven malignancy received clinical risk classification based on examination. On univariate analysis, EDNRB and risk classification were associated with diagnosis of dysplasia/cancer and remained significant on multivariate analysis (EDNRB: P = 0.047, risk classification: P = 0.008). Clinical risk classification identified dysplasia/cancer with a sensitivity of 71% and a specificity of 58%. The sensitivity of clinical risk classification combined with EDNRB methylation improved to 75%. EDNRB methylation in salivary rinses was independently associated with histologic diagnosis of premalignancy and malignancy and may have potential in classifying patients at risk for oral premalignant and malignant lesions in settings without access to a skilled dental practitioner. This may also potentially identify patients with premalignant and malignant lesions that do not meet the criteria for high clinical risk based on skilled dental examination
— id: 134406, year: 2010, vol: 3, page: 1093, stat: Journal Article,

Second-line age-adjusted International Prognostic Index in patients with advanced non-Hodgkin lymphoma after T-cell depleted allogeneic hematopoietic SCT
Perales, M-A; Jenq, R; Goldberg, J D; Wilton, A S; Lee, S S E; Castro-Malaspina, H R; Hsu, K; Papadopoulos, E B; van den Brink, M R M; Boulad, F; Kernan, N A; Small, T N; Wolden, S; Collins, N H; Chiu, M; Heller, G; O'Reilly, R J; Kewalramani, T; Young, J W; Jakubowski, A A
2010 Sep;45(9):1408-1416, Bone marrow transplantation
T-cell depleted allogeneic hematopoietic SCT (TCD-HSCT) have shown durable disease-free survival with a low risk of GVHD in patients with AML. We investigated this approach in 61 patients with primary refractory or relapsed non-Hodgkin lymphoma (NHL), who underwent TCD-HSCT from January 1992 through September 2004. Patients received myeloablative cytoreduction consisting of hyperfractionated total body irradiation, followed by either thiotepa and cyclophosphamide (45 patients) or thiotepa and fludarabine (16 patients). We determined the second-line age-adjusted International Prognostic Index score (sAAIPI) before transplant transplant. Median follow-up of surviving patients is 6 years. The 10-year OS and EFS were 50% and 43%, respectively. The relapse rate at 10 years was 21% in patients with chemosensitive disease and 52% in those with resistant disease at time of HSCT. Nine of the 18 patients who relapsed entered a subsequent CR. OS (P=0.01) correlated with the sAAIPI. The incidence of grades II-IV acute GVHD was 18%. We conclude that allogeneic TCD-HSCT can induce high rates of OS and EFS in advanced NHL with a low incidence of GVHD. Furthermore, the sAAIPI can predict outcomes and may be used to select the most appropriate patients for this type of transplant
— id: 134829, year: 2010, vol: 45, page: 1408, stat: Journal Article,

Identification of tyrosinase polymorphisms for use in melanoma risk assessment
Pervolaraki E; Lobach I; Belitskaya-Levy I; Ostrer H; Goldberg JD; Polsky D; Shapiro RL; Berman RS; Osman I; Manga P
2010 ;28(15S):?-? #8570, Journal of clinical oncology
Background: Most skin cancer-related deaths are due to malignant melanoma. Risk assessment criteria for melanoma currently include skin phenotype, family and sun exposure history, factors that are subject to observer and recall bias. Genetic markers of susceptibility have been identified in association studies; however little progress has been made in developing them to improve screening and identification of individuals at risk of melanoma. Tyrosinase (TYR), a known susceptibility gene and a determinant of skin pigmentation, was thus investigated further to characterize its association with melanoma susceptibility and to identify markers which can be used in a risk assessment model. Methods: The cohort consisted of 326 individuals diagnosed with melanoma and 400 control subjects. TYR was interrogated using fifteen tag single nucleotide polymorphisms (SNPs) spanning the gene and statistical association tests performed. Additionally, ancestry informative markers were utilized to correct for population genetic sub-structure. Haplotype analysis was performed to determine if specific regions of the gene contributed more significantly to susceptibility. Coding regions of the gene are currently being sequenced and identified variants will be tested for impact on enzymatic function. Results: Of the 15 SNPs, 8 were associated with melanoma; 4 with decreased risk (Odds ratios 0.41-0.71) and 4 with increased risk (Odds ratios 1.43-1.96). SNPs localized to 2 regions of the gene (spanning exon 1 to intron 2 and intron 3 to 4) with markers of increased as well as decreased susceptibility present in both areas. With the exception of one coding region variant, SNPs were localized to introns. Conclusions: SNPs localized to TYR may serve as useful biomarkers for determining susceptibility to melanoma. We are currently sequencing the gene in our population in order to identify additional and potentially more potent markers of melanoma susceptibility. Coding region variants are being characterized for their effect on protein stability and enzyme activity such that functional active variants (most likely to affect susceptibility to melanoma) can be identified and assessed for their utility in melanoma risk assessment
— id: 111554, year: 2010, vol: 28, page: ?, stat: Journal Article,

Identification of an autoantibody panel to separate lung cancer from smokers and nonsmokers
Rom, William N; Goldberg, Judith D; Addrizzo-Harris, Doreen; Watson, Heather N; Khilkin, Michael; Greenberg, Alissa K; Naidich, David P; Crawford, Bernard; Eylers, Ellen; Liu, Daorong; Tan, Eng M
2010 ;10:234-234, BMC cancer
BACKGROUND: Sera from lung cancer patients contain autoantibodies that react with tumor associated antigens (TAAs) that reflect genetic over-expression, mutation, or other anomalies of cell cycle, growth, signaling, and metabolism pathways. METHODS: We performed immunoassays to detect autoantibodies to ten tumor associated antigens (TAAs) selected on the basis of previous studies showing that they had preferential specificity for certain cancers. Sera examined were from lung cancer patients (22); smokers with ground-glass opacities (GGOs) (46), benign solid nodules (55), or normal CTs (35); and normal non-smokers (36). Logistic regression models based on the antibody biomarker levels among the high risk and lung cancer groups were developed to identify the combinations of biomarkers that predict lung cancer in these cohorts. RESULTS: Statistically significant differences in the distributions of each of the biomarkers were identified among all five groups. Using Receiver Operating Characteristic (ROC) curves based on age, c-myc, Cyclin A, Cyclin B1, Cyclin D1, CDK2, and survivin, we obtained a sensitivity = 81% and specificity = 97% for the classification of cancer vs smokers(no nodules, solid nodules, or GGO) and correctly predicted 31/36 healthy controls as noncancer. CONCLUSION: A pattern of autoantibody reactivity to TAAs may distinguish patients with lung cancer versus smokers with normal CTs, stable solid nodules, ground glass opacities, or normal healthy never smokers
— id: 110098, year: 2010, vol: 10, page: 234, stat: Journal Article,

Levels of elevated circulating endothelial cell decline after tumor resection in patients with pancreatic ductal adenocarcinoma
Sabbaghian, M Shirin; Rothberger, Gary; Alongi, Alexandra P; Gagner, Jean-Pierre; Goldberg, Judith D; Rolnitzky, Linda; Chiriboga, Luis; Hajdu, Cristina H; Zagzag, David; Basch, Ross; Shamamian, Peter
2010 Jul;30(7):2911-2917, Anticancer research
AIM: To evaluate circulating endothelial lineage cells (ELCs) as biomarkers of tumor neovascularization in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: ELCs were isolated from the peripheral blood of patients with PDAC (n=14) or controls (n=17) before and after tumor resection/surgery and quantified using flow cytometry. Vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were detected in tumor using immunohistochemistry and in plasma using an ELISA technique. RESULTS: Circulating ELC levels were increased in patients with PDAC compared to controls. After PDAC resection, ELC levels declined. ELC level increases were associated with cancer recurrence. VEGF and PlGF were identified in cancer cells and exocrine pancreas cells. Only PlGF was detected in tumor-associated inflammatory cells. Plasma levels of PlGF were higher in patients with PDAC compared to controls. CONCLUSION: Circulating ELCs are a potential biomarker of PDAC neovascularization, and PlGF may be an important target in treatment of PDAC
— id: 111825, year: 2010, vol: 30, page: 2911, stat: Journal Article,

Five-year Results of Preoperative Paclitaxel with Concurrent Radiation Therapy in Locally Advanced Breast Cancer: Pathological Response Predicts for Survival
Schneider, R. J.; Formenti, S. C.; Chakravarthy, A.; Adams, S.; Spicer, D.; Lymberis, S.; Goldberg, J. D.; Pietenpol, J. A.
2010 OCT 13 ;78(3):S219-S219, International journal of radiation oncology biology physics
— id: 114016, year: 2010, vol: 78, page: S219, stat: Journal Article,

High levels of Hsp90 cochaperone p23 promote tumor progression and poor prognosis in breast cancer by increasing lymph node metastases and drug resistance
Simpson, Natalie E; Lambert, W Marcus; Watkins, Renecia; Giashuddin, Shah; Huang, S Joseph; Oxelmark, Ellinor; Arju, Rezina; Hochman, Tsivia; Goldberg, Judith D; Schneider, Robert J; Reiz, Luiz Fernando Lima; Soares, Fernando Augusto; Logan, Susan K; Garabedian, Michael J
2010 Nov 1;70(21):8446-8456, Cancer research
p23 is a heat shock protein 90 (Hsp90) cochaperone located in both the cytoplasm and nucleus that stabilizes unliganded steroid receptors, controls the catalytic activity of certain kinases, regulates protein-DNA dynamics, and is upregulated in several cancers. We had previously shown that p23-overexpressing MCF-7 cells (MCF-7+p23) exhibit increased invasion without affecting the estrogen-dependent proliferative response, which suggests that p23 differentially regulates genes controlling processes linked to breast tumor metastasis. To gain a comprehensive view of the effects of p23 on estrogen receptor (ER)-dependent and -independent gene expression, we profiled mRNA expression from control versus MCF-7+p23 cells in the absence and presence of estrogen. A number of p23-sensitive target genes involved in metastasis and drug resistance were identified. Most striking is that many of these genes are also misregulated in invasive breast cancers, including PMP22, ABCC3, AGR2, Sox3, TM4SF1, and p8 (NUPR1). Upregulation of the ATP-dependent transporter ABCC3 by p23 conferred resistance to the chemotherapeutic agents etoposide and doxorubicin in MCF-7+p23 cells. MCF-7+p23 cells also displayed higher levels of activated Akt and an expanded phosphoproteome relative to control cells, suggesting that elevated p23 also enhances cytoplasmic signaling pathways. For breast cancer patients, tumor stage together with high cytoplasmic p23 expression more accurately predicted disease recurrence and mortality than did stage alone. High nuclear p23 was found to be associated with high cytoplasmic p23, therefore both may promote tumor progression and poor prognosis by increasing metastatic potential and drug resistance in breast cancer patients
— id: 114177, year: 2010, vol: 70, page: 8446, stat: Journal Article,

Establishing a Research Tissue Bank (TB): The Myeloproliferative Disorders Research Consortium (MPD-RC) Experience
Weinberg, R. S.; Silverman, L.; Goldberg, J. D.; Pahl, H. L.; Najfeld, V.; Prchal, J.; Marchioli, R.; Gonzalez, A.; Rambaldi, A.; Hoffman, R.
2010 SEP ;50:222A-222A, Transfusion
— id: 113645, year: 2010, vol: 50, page: 222A, stat: Journal Article,

The Young Women's Program: A health and wellness model to empower adolescents with physical disabilities
Xenakis, Nancy; Goldberg, Judith
2010 Apr;3(2):125-129, Disability & health journal
BACKGROUND: This article introduces a comprehensive health and wellness program that serves young women, ages 14 to 21, with physical disabilities. The program is a component of the Initiative for Women with Disabilities (IWD), a hospital-based center serving women with physical disabilities/conditions that offers accessible gynecology, primary care, physical therapy, nutrition consultations, exercise and fitness classes, and wellness and social work services. Recent literature has shown that young women with physical disabilities often face physical and emotional barriers to their own health and wellness. This group of adolescents often has difficulty developing a healthy image of their bodies, especially compared with their able-bodied peers. Unhealthy attitudes regarding the body image and sexuality of those with physical differences are often perpetuated by the media, peers, and parents. People with disabilities have become increasingly able to live fulfilling lives in recent decades. This is due largely to studies that have confirmed that once barriers are addressed and minimized, young women with physical disabilities lead active and productive lives and have much to contribute to society. METHODS: The goal of the Young Women's Program (YWP), established in 2006, is to help young women adopt healthy lifestyles by exposing them to a carefully planned curriculum. The program provides a variety of classes and workshops, expert instruction, and access to resources and a network of peers and mentors. The ultimate goal is for the participants to apply the concepts learned in the group sessions to identify and evaluate their personal goals and develop health and wellness plans for achieving these goals. RESULTS: Data were obtained from several sources: a self-administered program evaluation, program recruitment and retention statistics, and an assessment of whether individual health and wellness goals were achieved. All of these measures indicate a favorable response to the program structure and content. Participants are able to integrate and apply the learned concepts to alter aspects of their daily lifestyles and improve their self-confidence, self-worth, and self-competence. CONCLUSIONS: The results to date suggest that the YWP addresses the transitional challenges cited in the literature that young women with physical disabilities face from adolescence to adulthood. The structure of the program, which combines individual and group sessions, and the focused content appear to have a positive impact on the participants' lives by exposing them to experiences that promote self-determination and self-competence. By providing opportunities for socialization with peers and mentors and exposure to community resources, and by helping participants to develop self-care skills and to set goals for a healthy lifestyle, the program facilitates leading an independent life. The efficacy of the YWP will be determined by annual follow-up studies as participants enter adulthood
— id: 114861, year: 2010, vol: 3, page: 125, stat: Journal Article,

Abnormal P-selectin localization is crucial for the prothrombotic phenotype of the Gata1low model of myelofibrosis
Zetterberg E.; Verrucci M.; Martelli F.; Ghinassi B.; Zingariello M.; Rana R.A.; D'Amore E.; Goldberg J.D.; Migliaccio A.R.
2010 ;37:A4-A4, Pathophysiology of haemostatasis & thrombosis
Background/Aims: Patients with myelofibrosis have increased risk of bleeding and thrombosis. Increased numbers of platelet microparticles (PMP) and/or pathological platelet-neutrophil interactions has been suggested to underlie this trait. Megakaryocytes from patients, as well as from mice expressing low levels of Gata1(the Gata1low model of myelofibrosis) is characterized by an abnormal localization of P-selectin (P-sel). Whether these mice also develop thrombosis is not known. Aims: The aim of this study was to determine whether Gata1low mice develop thrombosis with age and, in this case, the role played by P-sel. Materials and methods: Gata1low mice were crossed with P-selnull mice according to standard protocols and Gata1lowP-selWT, Gata1lowP-selnull and Gata1WTPselnull or Gata1WTP-selWT littermates obtained. Blood platelet counts (ptl) and PMP counts were compared among the four experimental groups (Table). The presence of thrombosis was determined according to standard histological criteria. Results: Gata1WT mice had significantly greater platelet levels than Gata1low mice regardless of P-sel (Wilcoxon rank test, p <=0.0001). PMP were found to be reduced in Gata1low mice compared to Gata1WT littermates (Table I). Gata1WTP-selnull and Gata1low/P-selnull littermates had also reduced numbers of PMP. P-sel was only expressed by PMP from Gata1WTP-selWT mice. Thrombosis was only found in adult (5-9 months) and old (10-16 months) Gata1lowP-selWT mice. The majority of the thrombi were found in adult mice (67% vs 33% of organs affected). Conclusions: The maturation defect induced in megakaryocytes by the Gata1low mutation leads to a pro-thrombotic state detectable from 5 months of age. The presence of the P-selnull mutation rescues the thrombotic phenotype but not the ptl or PMP deficiency induced by the Gata1low mutation. Thus, abnormal P-sel localization, rather than altered PMP numbers, appears to be responsible for the thrombogenicity induced by the Gata1low mutation. These results suggest P-sel as possible target for therapeutic prevention of thrombosis in PMF
— id: 113674, year: 2010, vol: 37, page: A4, stat: Journal Article,

Lack of Hormone Receptor Expression is Associated with Pathological Response in Locally Advanced Breast Cancer Patients Treated with Neoadjuvant Concurrent Chemoradiation
Adams, S; Donach, M; Singh, B; Goldberg, JD; Formenti, SC
2009 NOV ;75(3):S220-S221, International journal of radiation oncology biology physics
— id: 106177, year: 2009, vol: 75, page: S220, stat: Journal Article,

Effect of mebendazole on melanoma xenograft growth through targeting of bcl-2
Doudican N.A.; Pennell R.; Tu T.; Liebes L.; Pavlick A.; Berman R.; Shapiro R.; Goldberg J.D.; Osman I.; Orlow S.
2009 ;27(15 Suppl 1):9075-9075, Journal of clinical oncology
Background: Defects in apoptosis are thought to contribute to melanoma chemoresistance, making the anti-apoptotic protein Bcl-2 an attractive therapeutic target. We identified mebendazole (MBZ), a microtubule binding agent, as an inducer of melanoma cytotoxicity via a Bcl-2 dependent mechanism in vitro (Mol Cancer Res, Aug 2008). In the present study, we assessed the effect of MBZ on human melanoma tumor growth and progression in a mouse xenograft model and compared the ability of MBZ to inhibit growth of cultured melanoma cells to that of oblimersen (OBL), an antisense drug targeting Bcl-2. Methods: Growth of human M-14 melanoma xenografts in mice administered MBZ orally at doses from 0.1 to 2 mg were compared to tumor growth in mice receiving 100mg/kg intraperitoneal temozolomide (TMZ) or vehicle alone. Tumor diameter, volume, histopathology, and immunohistochemical staining of caspase 3 and Ki67 were assessed. Bcl-2 phosphorylation was determined by immunoblotting. MBZ and OBL-induced melanoma growth inhibition was analyzed by MTT assay. Results: Anti-melanoma effects of MBZ were dose- dependent up to 1 mg which displayed a 72% reduction in tumor volume compared to vehicle treated mice. This reduction in volume was accompanied by a 46% decrease in proliferating cells and an 81% increase in apoptotic cells. Moreover, 1 mg MBZ inhibited tumor growth as effectively as high dose TMZ, the current melanoma standard of care. Orally administered MBZ treatment resulted in Bcl-2 phosphorylation in vivo, further confirming its mechanism of action. MBZ inhibited growth of melanoma cells in culture more effectively than OBL with GI50 values of 0.32 uM and 7.45 uM, respectively. Conclusions: MBZ safely and effectively inhibits melanoma growth and progression in a xenograft model. A phase II clinical trial investigating MBZ's utility as adjuvant therapy in patients with stage IV, resected melanoma is planned
— id: 111807, year: 2009, vol: 27, page: 9075, stat: Journal Article,

Association of MDM2 SNP309, age of onset, and gender in cutaneous melanoma
Firoz, Elnaz F; Warycha, Melanie; Zakrzewski, Jan; Pollens, Danuta; Wang, Guimin; Shapiro, Richard; Berman, Russell; Pavlick, Anna; Manga, Prashiela; Ostrer, Harry; Celebi, Julide Tok; Kamino, Hideko; Darvishian, Farbod; Rolnitzky, Linda; Goldberg, Judith D; Osman, Iman; Polsky, David
2009 Apr 1;15(7):2573-2580, Clinical cancer research
PURPOSE: In certain cancers, MDM2 SNP309 has been associated with early tumor onset in women. In melanoma, incidence rates are higher in women than in men among individuals less than 40 years of age, but among those older than 50 years of age, melanoma is more frequent in men than in women. To investigate this difference, we examined the association among MDM2 SNP309, age at diagnosis, and gender among melanoma patients. EXPERIMENTAL DESIGN: Prospectively enrolled melanoma patients (N = 227) were evaluated for MDM2 SNP309 and the related polymorphism, p53 Arg72Pro. DNA was isolated from patient blood samples, and genotypes were analyzed by PCR-restriction fragment length polymorphism. Associations among MDM2 SNP309, p53 Arg72Pro, age at diagnosis, and clinicopathologic features of melanoma were analyzed. RESULTS: The median age at diagnosis was 13 years earlier among women with a SNP309 GG genotype (46 years) compared with women with TG+TT genotypes (59 years; P = 0.19). Analyses using age dichotomized at each decade indicated that women with a GG genotype had significantly higher risks of being diagnosed with melanoma at ages <50 years compared with women >or=50 years, but not when the comparison was made between women <60 and >or=60 years. At ages <50 years, women with a GG genotype had a 3.89 times greater chance of being diagnosed compared with women with TG+TT genotypes (P = 0.01). Similar observations were not seen among men. CONCLUSIONS: Our data suggest that MDM2 may play an important role in the development of melanoma in women. The MDM2 SNP309 genotype may help identify women at risk of developing melanoma at a young age
— id: 104875, year: 2009, vol: 15, page: 2573, stat: Journal Article,

Kinetin in familial dysautonomia carriers: implications for a new therapeutic strategy targeting mRNA splicing
Gold-von Simson, Gabrielle; Goldberg, Judith D; Rolnitzky, Linda M; Mull, James; Leyne, Maire; Voustianiouk, Andrei; Slaugenhaupt, Susan A; Axelrod, Felicia B
2009 Mar;65(3):341-346, Pediatric research
Familial dysautonomia (FD) is caused by an intronic splice mutation in the IkappaB kinase-associated protein gene (IKBKAP) that leads to partial skipping of exon 20 and tissue-specific reduction of IkappaB kinase-associated protein/elongator protein 1 (IKAP/ELP-1 protein). Kinetin increases IKBKAP mRNA and protein expression in FD cell lines. To determine whether oral kinetin alters IKBKAP splicing in vivo, we administered kinetin to 29 healthy carriers of the major FD mutation for 8 d. Adverse effects, kinetin, and IKBKAP mRNA levels were monitored. In the highest dosing cohorts (23.5 mg/kg/d), the target plasma kinetin level was achieved in 91% of subjects at 2 h. After 8 d, IKBKAP mRNA expression in leukocytes increased as kinetin levels increased. There is a linear association between log plasma kinetin level and corresponding log change from baseline in IKBKAP mRNA expression that allows estimation of IKBKAP mRNA levels because of kinetin ingestion. Adverse effects were transient and mild. This is the first report of in vivo IKBKAP splicing modification and strongly suggests kinetin's therapeutic potential in FD and perhaps in other splicing disorders. Furthermore, our findings support our hypothesis that treatments, which target a particular splicing mutation, can be successfully developed
— id: 104339, year: 2009, vol: 65, page: 341, stat: Journal Article,

A Multicenter, Open Label Phase I/II Study of CEP701 (Lestaurtinib) in Adults with Myelofibrosis; a Report On Phase I: A Study of the Myeloproliferative Disorders Research Consortium (MPD-RC)
Hexner, E; Goldberg, JD; Prchal, JT; Demakos, EP; Swierczek, S; Weinberg, RS; Tripodi, J; Najfeld, V; Carroll, M; Marchioli, R; Silverman, LR; Hoffman, R
2009 NOV 20 ;114(22):314-314, Blood
— id: 109974, year: 2009, vol: 114, page: 314, stat: Journal Article,

Correlation of novel molecular markers in patients with myeloproliferative neoplasms
Kaufmann K.; Swierczek S.; Shang S.; Gruender A.; Singer Weinberg R.; Rambaldi A.; Marchioli R.; Hickmann K.; Goldberg J.D.; Prchal J.T.; Pahl H.L.
2009 ;114(22):?-? #4968, Blood
— id: 112214, year: 2009, vol: 114, page: ?, stat: Journal Article,

Developing genetic markers for melanoma risk assessment
Manga P.; Goldberg J.D.; Belitskaya-Levy I.; Lobach I.; Polsky D.; Pavlick A.; Shapiro R.; Berman R.; Osman I.; Ostrer H.
2009 ;27(15 Suppl 1):9046-9046, Journal of clinical oncology
Background: Risk assessment for melanoma is currently based on phenotype, family and exposure history. This approach is subject to recall bias and excludes at-risk groups such as those with darker skin pigmentation. Poorly stratified risk pools also result in unnecessary dermatologist visits and biopsies for those at lower risk. Use of genetic markers may improve risk assessment; however few susceptibility markers have been developed to date. There have been a number of reports of association between melanoma and genetic markers though few have been replicated or validated. In addition, these studies frequently utilized specific coding region variants as markers and failed to test the entire gene. We have therefore assembled a case-control cohort in which to search for potential biomarkers for melanoma risk by interrogating genes using recently developed tools for genetic analysis. A pilot study was performed to test the utility of our cohort. Methods: A cohort of 326 individuals diagnosed with melanoma and treated at the New York University Langone Medical Center and 400 controls obtained from the New York Cancer project was assembled. Candidate genes were selected based on involvement in determining melanoma predisposition factors (skin pigmentation and DNA repair capability) and previous studies showing association. Three genes, ERCC1, ERCC4 (DNA repair) and MATP (skin pigmentation) were selected. Tag Single Nucleotide Polymorphisms (tSNPs) were selected using Haploview (Hapmap.org) and DNA genotyped (Sequenom Inc, San Diego, CA). Odds ratios and confidence intervals were computed for each SNP. Results: An association was found between SNP rs11615 at the ERCC1 locus and melanoma (Odds ratio = 1.718, 95% Confidence interval: 1.259 - 2.343 for TT vs TC/CC). Conclusions: A tSNP approach is thus useful in identifying associations in our melanoma case-control cohort. Sequence variation at the ERCC1 locus contributes to melanoma risk and the gene will now be screened for clinically useful susceptibility biomarkers. Additional DNA repair and pigmentation genes will also be interrogated using this approach. Genes found to be associated with melanoma will be screened by high- density SNP analysis to identify the most appropriate biomarker/s for use in risk assessment
— id: 111805, year: 2009, vol: 27, page: 9046, stat: Journal Article,

A Phase I Study of LBH589, a Novel Histone Deacetylase Inhibitor in Patients with Primary Myelofibrosis (PMF) and Post-Polycythemia/Essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)
Mascarenhas, J; Wang, XL; Rodriguez, A; Xu, MJ; Gorman, E; Zhang, WY; Goldberg, JD; Najfeld, V; Hoffman, R
2009 NOV 20 ;114(22):130-131, Blood
— id: 109970, year: 2009, vol: 114, page: 130, stat: Journal Article,

Evaluation of the melanocortin-1-receptor gene in melanoma predisposition, progression and recurrence
Sidash S; Ostrer H; Goldberg JD; Belitskaya-Levy I; Lobach I; Polsky D; Shapiro RL; Berman RS; Osman I; Manga P
2009 ;27:15S-15S, Journal of clinical oncology
— id: 102306, year: 2009, vol: 27, page: 15S, stat: Journal Article,

Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer
Silvera, Deborah; Arju, Rezina; Darvishian, Farbod; Levine, Paul H; Zolfaghari, Ladan; Goldberg, Judith; Hochman, Tsivia; Formenti, Silvia C; Schneider, Robert J
2009 Jul;11(7):903-908, Nature cell biology
Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer. IBC lethality derives from generation of tumour emboli, which are non-adherent cell clusters that rapidly spread by a form of continuous invasion known as passive metastasis. In most cancers, expression of E-cadherin, an epithelial marker, is indicative of low metastatic potential. In IBC, E-cadherin is overexpressed and supports formation of tumour emboli by promoting tumour cell interactions rather than adherence to stroma. E-cadherin, a surface component of adherens junctions, is anchored by interaction with p120 catenin (p120). We show that the unique pathogenic properties of IBC result in part from overexpression of the translation initiation factor eIF4GI in most IBCs. eIF4GI reprograms the protein synthetic machinery for increased translation of mRNAs with internal ribosome entry sites (IRESs) that promote IBC tumour cell survival and formation of tumour emboli. Overexpression of eIF4GI promotes formation of IBC tumour emboli by enhancing translation of IRES-containing p120 mRNAs. These findings provide a new understanding of translational control in the development of advanced breast cancer
— id: 100610, year: 2009, vol: 11, page: 903, stat: Journal Article,

Thrombopoietin Receptor (MPL) Genotype Modifies the Myeloproliferative Phenotype in a JAK2 V617F Transgenic Mouse Model of Polycythemia Vera
Spivak, VJL; Williams, DM; Stein, BL; Rogers, O; Hochman, T; Goldberg, JD; Zhao, WM; Zhao, ZZJ; Moliterno, AR
2009 NOV 20 ;114(22):398-399, Blood
— id: 109976, year: 2009, vol: 114, page: 398, stat: Journal Article,

Clonal analyses define the relationships between chromosomal abnormalities and JAK2V617F in patients with Ph-negative myeloproliferative neoplasms
Wang, Xiaoli; LeBlanc, Amanda; Gruenstein, Steven; Xu, Mingjiang; Mascarenhas, John; Panzera, Brenda; Wisch, Nathaniel; Parker, Charles; Goldberg, Judith D; Prchal, Josef; Hoffman, Ronald; Najfeld, Vesna
2009 Oct;37(10):1194-1200, Experimental hematology
OBJECTIVE: JAK2V617F occurs in approximately 93% of patients with polycythemia vera and approximately 50% of patients with either primary myelofibrosis or essential thrombocythemia. Chromosomal abnormalities are detected in 50% of patients with primary myelofibrosis, 29% with polycythemia vera, and 8% to 10% with essential thrombocythemia. The relationship between the presence of such chromosomal abnormalities and the JAK2V617 allele burden, and the role that each of these genetic events play in the origins and progression of the myeloproliferative neoplasms (MPNs), remain unclear. MATERIALS AND METHODS: Individual hematopoietic colonies were assayed in vitro from the CD34(+) cells of six JAK2V617F-positive MPN patients with marker chromosomal abnormalities. Colonies were simultaneously analyzed for JAK2 genotype and chromosomal abnormalities. RESULTS: Among the 248 colonies assayed from cultures containing 500 CD34(+) cells, chromosomal abnormalities were detected in 5% of colonies with wild-type JAK2, 32% of JAK2V617F heterozygous colonies and 56% of JAK2V617F homozygous colonies. Overall, 92% of chromosomally abnormal colonies were also JAK2V617F homozygous. Although 54 colonies contained wild-type JAK2 exclusively, 4 of these colonies were characterized by chromosomal abnormalities. CONCLUSION: This study indicates that MPN hematopoietic progenitor cells do not necessarily always acquire genetic events in the same sequence. (Chromosomally abnormal progenitor cells are closely associated with JAK2V617F homozygosity; p=0.0001.). Chromosomal abnormalities such as +8, +9 can occasionally precede acquisition of JAK2V617F. These findings support the existence of earlier genetic events that precede JAK2V617F or cytogenetic abnormalities in MPN hematopoietic progenitor cells
— id: 133714, year: 2009, vol: 37, page: 1194, stat: Journal Article,

Developing a multidisciplinary prospective melanoma biospecimen repository to advance translational research
Wich, Lindsay G; Hamilton, Heather K; Shapiro, Richard L; Pavlick, Anna; Berman, Russell S; Polsky, David; Goldberg, Judith D; Hernando, Eva; Manga, Prashiela; Krogsgaard, Michelle; Kamino, Hideko; Darvishian, Farbod; Lee, Peng; Orlow, Seth J; Ostrer, Harry; Bhardwaj, Nina; Osman, Iman
2009 ;1(1):35-43, American Journal of Translational Research
Several challenges face the development and operation of a biospecimen bank linked to clinical information, a critical component of any effective translational research program. Melanoma adds particular complexity and difficulty to such an endeavor considering the unique characteristics of this malignancy. We describe here a review of biospecimen bank and our experience in establishing a multi-disciplinary, prospective, integrated clinicopathological-biospecimen database in melanoma. The Interdisciplinary Melanoma Cooperative Group (IMCG), a prospective clinicopathological and biospecimen database, was established at the New York University (NYU) Langone Medical Center. With patients' informed consent, biospecimens from within and outside NYU, clinicopathological data, and follow-up information are collected using developed protocols. Information pertaining to biospecimens is recorded in 35 fields, and clinicopathological information is recorded in 371 fields within 5 modules in a virtual network system. Investigators conducting research utilizing the IMCG biospecimen resource are blind to clinicopathological information, and molecular data generated using biospecimens are linked independently with clinicopathological data by biostatistics investigators. This translational research enterprise acts as a valuable resource to efficiently translate laboratory discoveries to the clinic
— id: 105566, year: 2009, vol: 1, page: 35, stat: Journal Article,

Abnormal P-Selectin Localization During Megakaryocyte Development Determines Thrombosis in the Gata1(low) Model of Myelofibrosis
Zetterberg, E; Verrucci, M; Martelli, F; Ghinassi, B; D'Amore, E; Goldberg, JD; Migliaccio, AR
2009 NOV 20 ;114(22):757-757, Blood
— id: 109989, year: 2009, vol: 114, page: 757, stat: Journal Article,

Systematic missing-at-random (SMAR) design and analysis for translational research studies
Belitskaya-Levy, Ilana; Shao, Yongzhao; Goldberg, Judith D
2008 ;4(1):1- 26, International Journal of Biostatistics
Translational research studies often involve a central study (e.g. clinical trial, cohort of patients, etc.) and multiple investigators who are each interested in addressing different research questions using the same patient population. However, it is often impossible for the investigators to include all patients in all of the ancillary translational research substudies that are part of the main study. This arises due to time and budgetary constraints and other logistical considerations. In this paper, we propose a prospective Systematic Missing-At-Random study design (SMAR) with planned partially missing covariates collected using a nested random sampling scheme that allows an integrated statistical analysis across all domains of data. We propose an algorithm for data analysis that incorporates the features of the design. We show that the SMAR design is computationally and statistically efficient as well as cost effective using simulation studies and a published data example. An extension to a two-stage prospective-retrospective design is discussed.
— id: 136935, year: 2008, vol: 4, page: 1, stat: Journal Article,

IKBKAP mRNA in peripheral blood leukocytes: a molecular marker of gene expression and splicing in familial dysautonomia
Gold-von Simson, Gabrielle; Leyne, Maire; Mull, James; Rolnitzky, Linda M; Goldberg, Judith D; Berlin, Dena; Axelrod, Felicia B; Slaugenhaupt, Susan A
2008 Feb;63(2):186-190, Pediatric research
The common familial dysautonomia (FD) mutation results in tissue specific mis-splicing with reduced amount of wild-type (WT) IkappaB kinase associated protein gene (IKBKAP) mRNA and ELP1. ELP1 is a subunit of Elongator, formerly called the IkappaB kinase associated protein (IKAP) protein. We measured IKBKAP mRNA in peripheral blood leukocytes to determine whether FD subjects and carriers have characteristic levels. Estimated mean IKBKAP mRNA levels, measured by quantitative PCR and expressed as amount relative to the noncarrier average, were significantly different for the two groups when not adjusted for age and sex (p < 0.001): FD subjects 0.23, 95% confidence interval (CI) (0.19, 0.28); carriers 0.58, 95% CI (0.50, 0.68); or adjusted for age and sex (p < 0.001): FD subjects 0.21, 95% CI (0.16, 0.26); carriers 0.66, 95% CI (0.55, 0.79). Comparison of IKBKAP mRNA levels of the 22 FD subjects and their related carriers showed a strong correlation, providing evidence for genetic control of splicing efficiency. IKBKAP mRNA levels were not higher in those subjects using tocotrienols or epigallocatechin gallate. Levels of IKBKAP mRNA in peripheral blood leukocytes can be used to assess molecular response to therapies aimed at enhancing exon 20 inclusion and increasing cellular levels of ELP1/IKAP
— id: 78635, year: 2008, vol: 63, page: 186, stat: Journal Article,

Survival after surgery in stage IA and IB non-small cell lung cancer
Ost, David; Goldberg, Judith; Rolnitzky, Linda; Rom, William N
2008 Mar 1;177(5):516-523, American journal of respiratory & critical care medicine
RATIONALE: Whether histologic subtype of non-small cell lung cancer (NSCLC) has an important effect on prognosis after surgery is unknown. OBJECTIVES: We hypothesized that we could predict mortality more effectively by integrating precise tumor size and histology rather than relying on conventional staging. METHODS: We used the SEER (Surveillance, Epidemiology, and End Results) registry. Inclusion criteria were as follows: (1) primary squamous cell or adenocarcinoma; (2) potentially curative surgery, defined as a lobectomy or bilobectomy; (3) lymph node dissection performed; and (4) pathologic stage IA or IB. MEASUREMENTS AND MAIN RESULTS: From 1988 to 2000, 7,965 patients were included. For both all-cause and lung cancer-associated mortality, tumor size demonstrated the strongest association (log-rank P < 0.0001 for each). When tumors were small (</=2 cm), lung cancer-associated mortality was similar for adenocarcinoma when compared with squamous cell carcinoma. When tumors were 3 cm or larger in size, lung cancer-associated mortality was higher for adenocarcinoma. The increased risk of lung cancer-associated mortality with adenocarcinoma was more pronounced in those younger than 65 years. Survival prediction using precise size and histology had much better discriminatory power than conventional TNM (tumor-node-metastasis) staging (P = 0.005). CONCLUSIONS: Staging that takes into account size, histology, late recurrence risk, and patient age is more accurate than the current TNM system and is clinically relevant because improved prediction can facilitate better decisions on the use of adjuvant chemotherapy
— id: 76334, year: 2008, vol: 177, page: 516, stat: Journal Article,

A hybrid Bayesian-frequentist approach to evaluate clinical trial designs for tests of superiority and non-inferiority
Shao, Yongzhao; Mukhi, Vandana; Goldberg, Judith D
2008 Feb 20;27(4):504-519, Statistics in medicine
Specification of the study objective of superiority or non-inferiority at the design stage of a phase III clinical trial can sometimes be very difficult due to the uncertainty that surrounds the efficacy level of the experimental treatment. This uncertainty makes it tempting for investigators to design a trial that would allow testing of both superiority and non-inferiority hypotheses. However, when a conventional single-stage design is used to test both hypotheses, the sample size is based on the chosen primary objective of either superiority or non-inferiority. In this situation, the power of the test for the secondary objective can be low, which may lead to a large loss of resources. Potentially low reproducibility is another major concern for the single-stage design in phase III trials, because significant findings of confirmatory trials are required to be reproducible. In this paper, we propose a hybrid Bayesian-frequentist approach to evaluate reproducibility and power in single-stage designs for phase III trials to test both superiority and non-inferiority. The essence of the proposed approach is to express the uncertainty that surrounds the efficacy of the experimental treatment as a probability distribution. Then one can use Bayes formula with simple graphical techniques to evaluate reproducibility and power adequacy
— id: 79289, year: 2008, vol: 27, page: 504, stat: Journal Article,

Immunohistochemical study of fibrosis and adenocarcinoma in dominant-negative p53 transgenic mice exposed to chrysotile asbestos and benzo(a)pyrene
Yee, Herman; Yie, Ting-An; Goldberg, Judith; Wong, Kam Meng Tchou; Rom, William N
2008 ;27(4):267-276, Journal of environmental pathology, toxicology & oncology
We evaluated the mechanisms using immunohistochemistry whereby chrysotile asbestos and benzo(a)pyrene (BaP) instilled intratracheally into lung-specific dominant-negative p53 (dnp53) mice might interact in causing lung carcinomas and fibrosis. Chrysotile asbestos and benzo(a)pyrene (BaP) were instilled intratracheally into lung-specific dominant-negative p53 (dnp53) and control mice. The mice were sacrificed at 12 months and their lungs examined for lung carcinomas and fibrosis. Immunostains for proteins related to apoptosis, fibrogenesis, matrix remodeling and inflammation were performed. The dnp53 mice had increased numbers of lung adenocarcinomas with BaP alone and the combination of chrysotile and BaP (the latter was additive but not significant). Several atypical adenomatous hyperplasia lesions were found in the combined treatment group. dnp53 and FVBN control mice developed nodular buds of fibrotic lung tissue after chrysotile asbestos exposure that were localized in respiratory bronchioles; these lesions had significant increases in immunohistochemical staining for TGF-beta, MMP-7 and -9, MIG-1, and SDF-1. Fibrotic lesions in mice exposed to chrysotile had increased collagen demonstrated by picrosirius red staining. The dnp53 mice with adenocarcinomas had increased SDF-1, TGF-beta, MMP-9 and -7, Cyclin D, and MIG-1 immunostaining in the chrysotile and combined treatment groups. We conclude that BaP and the combination of BaP plus chrysotile asbestos are potent inducers of adenocarcinoma in dnp53 mice and that the inflammatory cytokines and proteases MMP-7 and -9, MIG-1, and SDF-1, and growth factors Cyclin D and TGF-beta are increased in the specific lesions
— id: 94494, year: 2008, vol: 27, page: 267, stat: Journal Article,

A phase I study of the proteasome inhibitor bortezomib in patients with myelofibrosis
Barosi, G; Gattoni, E; Barbui, T; Vannucchi, AM; Rambaldi, A; Silverman, L; Goldberg, J; Marchioli, R; Hoffman, R
2007 NOV 16 ;110(11):1036A-1036A, Blood
— id: 76186, year: 2007, vol: 110, page: 1036A, stat: Journal Article,

Gene profiling of normal human bronchial epithelial cells in response to asbestos and benzo(a)pyrene diol epoxide (BPDE)
Belitskaya-Levy, Ilana; Hajjou, Mustapha; Su, Wei-cheng; Yie, Ting-An; Tchou-Wong, Kam-Meng; Tang, Moon-shong; Goldberg, Judith D; Rom, William N
2007 ;26(4):281-294, Journal of environmental pathology, toxicology & oncology
Asbestos and benzo(a)pyrene diol epoxide (BPDE) are pulmonary carcinogens with synergistic interaction in causing lung cancer. We used Affymetrix microarrays to study gene modulation in vitro using normal human bronchial epithelial cells exposed to chrysotile asbestos and/or BPDE for 4 or 24 h. Linear models were used to compare treated cells to controls at each time point to identify statistically significant up- or downregulation of genes. Profiles of genes regulated by chrysotile were dominated by cytokines, growth factors, and DNA damage. Profiles of genes with BPDE and chrysotile regulation were correlated with proliferation, DNA damage recognition and nucleotide-excision repair, cytokines, and apoptosis. Chemokines, growth-regulated oncogene-alpha (Gro-alpha, CXCL-1), and IL-8, were significantly increased, and these had previously been observed in bronchoalveolar lavage from asbestos workers or in animal models. Interestingly, the Hermansky-Pudlak gene, which is mutated in an autosomal recessive form of pulmonary fibrosis, was downregulated threefold by BPDE at 4 h. This is an interesting example of gene (Hermansky-Pudlak syndrome) and environment (BPDE) interaction. Transcription factors, including activating transcription factor 3 and Cbp/p300-interacting transactivator, were upregulated by chrysotile. Real Time PCR for IL-8, ATF-3, GADD45B, CXC Ligand 1, and CTGF compared to GAPDH validated microarray findings at 24 h. These in vitro findings in NHBE cells model environment-gene interaction for asbestos and BPDE, highlighting effects of inflammation, fibrosis, proliferation, and DNA damage recognition and repair
— id: 76391, year: 2007, vol: 26, page: 281, stat: Journal Article,

A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer
Braunstein, Steve; Karpisheva, Ksenia; Pola, Carolina; Goldberg, Judith; Hochman, Tsivia; Yee, Herman; Cangiarella, Joan; Arju, Rezina; Formenti, Silvia C; Schneider, Robert J
2007 Nov 9;28(3):501-512, Molecular cell
Translational regulation is critical in cancer development and progression. Translation sustains tumor growth and development of a tumor vasculature, a process known as angiogenesis, which is activated by hypoxia. Here we first demonstrate that a majority of large advanced breast cancers overexpress translation regulatory protein 4E-BP1 and initiation factor eIF4G. Using model animal and cell studies, we then show that overexpressed 4E-BP1 and eIF4G orchestrate a hypoxia-activated switch from cap-dependent to cap-independent mRNA translation that promotes increased tumor angiogenesis and growth at the level of selective mRNA translation. Elevated levels of 4E-BP1 trigger hypoxia inhibition of cap-dependent mRNA translation at high-oxygen levels and, with eIF4G, increase selective translation of mRNAs containing internal ribosome entry sites (IRESs) that include key proangiogenic, hypoxia, and survival mRNAs. The switch from cap-dependent to cap-independent mRNA translation facilitates tumor angiogenesis and hypoxia responses in animal models
— id: 75671, year: 2007, vol: 28, page: 501, stat: Journal Article,

Prospective trial of individual optimal positioning (prone versus supine) for whole breast radiotherapy: results of 194 patients
Formenti, SC; Guth, AA; Axelrod, DM; Goldberg, JD; DeWyngaert, JK
2007 DEC ;106(1):S194-S194, Breast cancer research & treatment
— id: 75805, year: 2007, vol: 106, page: S194, stat: Journal Article,

Prospective trial of individual optimal positioning (Prone versus supine) for whole breast radiotherapy: Results of the first 168 patients
Formenti, SC; Parhar, PK; Goldberg, JD; DeWyngaert, JK
2007 JAN ;69(3):S74-S74, International journal of radiation oncology biology physics
— id: 87192, year: 2007, vol: 69, page: S74, stat: Journal Article,

Phase I-II trial of prone accelerated intensity modulated radiation therapy to the breast to optimally spare normal tissue
Formenti, Silvia C; Gidea-Addeo, Daniela; Goldberg, Judith D; Roses, Daniel F; Guth, Amber; Rosenstein, Barry S; DeWyngaert, Keith J
2007 Jun 1;25(16):2236-2242, Journal of clinical oncology
PURPOSE: To report the clinical feasibility of a trial of accelerated whole-breast intensity modulated radiotherapy, with the patient in prone position, optimally to spare the heart and lung. PATIENTS AND METHODS: Patients with stages I or II breast cancer, excised by breast conserving surgery with negative margins, were eligible for this institutional review board-approved prospective trial. Computed tomography simulation was performed with the patient prone on a dedicated breast board, in the exact position used for treatment. A dose of 40.5 Gy, delivered at 2.7 Gy in 15 fractions, was prescribed to the index breast with an additional concomitant boost of 0.5 Gy delivered to the tumor bed, for a total dose of 48 Gy to the lumpectomy site. Physics constraints consisted of limiting 5% of the heart volume to receive > or = 18 Gy and < or = 10% of the ipsilateral lung volume to receive > or = 20 Gy. RESULTS: Between September 2003 and August 2005, 91 patients were enrolled on the study. Median length of follow-up was 12 months (range, 1 to 28 months). In all patients the technique was feasible and heart and lung sparing was achieved as prescribed by the protocol. Acute toxicities consisting mostly of reversible grades 1-2 skin dermatitis (67%) and fatigue (18%) occurred in 75 patients. One patient sustained a regional recurrence rapidly followed by distant metastases. CONCLUSION: Accelerated whole breast intensity modulated radiotherapy in the prone position is feasible and it permits a drastic reduction in the volume of lung and heart tissue exposed to significant radiation.
— id: 72870, year: 2007, vol: 25, page: 2236, stat: Journal Article,

S-adenosylmethionine as a biomarker for the early detection of lung cancer
Greenberg, Alissa K; Rimal, Binaya; Felner, Kevin; Zafar, Subooha; Hung, Jerry; Eylers, Ellen; Phalan, Brendan; Zhang, Meng; Goldberg, Judith D; Crawford, Bernard; Rom, William N; Naidich, David; Merali, Salim
2007 Oct;132(4):1247-1252, Chest
BACKGROUND: S-Adenosylmethionine (AdoMet) is a major methyl donor for transmethylation reactions and propylamine donor for the biosynthesis of polyamines in biological systems, and therefore may play a role in lung cancer development. We hypothesized that AdoMet levels were elevated in patients with lung cancer and may prove useful as a biomarker for early lung cancer. METHODS: High-performance liquid chromatography was used to analyze plasma AdoMet levels in triplicate samples from 68 patients. This included 13 patients with lung cancer, 33 smokers with benign lung disease, and 22 healthy nonsmokers. The three groups of subjects were compared with respect to the distribution of demographic and disease characteristics and AdoMet levels. Distributions were examined using summary statistics and box plots, and nonparametric analysis of variance procedures. RESULTS: Serum AdoMet levels were elevated in patients with lung cancer as compared to smokers with benign lung disorders and healthy nonsmokers. There were no significant correlations between AdoMet levels and tumor cell types, nodule size, or other demographic variables. CONCLUSIONS: Our data demonstrate that plasma levels of AdoMet are significantly elevated in patients with lung cancer. Plasma AdoMet levels may prove to be a useful tool for the diagnosis of early lung cancer, in combination with chest CT. Registered at: clinicaltrials.gov (NCT00301119)
— id: 74778, year: 2007, vol: 132, page: 1247, stat: Journal Article,

Histologic features are important prognostic indicators in early stages lung adenocarcinomas
Yim, Joon; Zhu, Lee-Ching; Chiriboga, Luis; Watson, Heather N; Goldberg, Judith D; Moreira, Andre L
2007 Feb;20(2):233-241, Modern pathology
This study attempts to evaluate the clinicopathologic features of mixed subtype adenocarcinomas and the prognostic implications of histopathology classifications. Surgical specimens from 141 patients with clinical stage I or II lung adenocarcinoma during the period 1992-2004 were included. These cases were classified into four groups defined by the extent of the bronchioloalveolar carcinoma component: group I: pure bronchioloalveolar carcinoma; group II: mixed subtype with predominant bronchioloalveolar carcinoma component and </=5 mm invasive component; group III: mixed subtype with bronchioloalveolar carcinoma component and >5 mm invasive component; group IV: invasive carcinoma with no bronchioloalveolar carcinoma component. Descriptive statistics were used to examine the groups with respect to age, tumor size, lymph node metastasis, and Ki-67 and p53 expression levels. Death rate for the groups was obtained by patient's charts and from the National Death Index database. The population was similar in age, tumor size and lymph node metastasis. Immunohistochemical results showed that the mean Ki-67 labeling and the amount of p53 overexpression had the same trend of increasing mean values or positive results from groups I to IV. The reported proportion of deaths ranged from 0% for groups I and II, 20% in patients with predominant invasive component with bronchioloalveolar carcinoma (group III), and 18% in patients with invasive carcinomas and no bronchioloalveolar carcinoma component (group IV). The difference between the proportion of patients with reported deaths in the time period of this study in the combined greater than 5 mm+pure invasive groups (groups III, IV), and the <5 mm+noninvasive groups (groups I, II) is statistically significant. These results suggest that histological features may be useful in defining categories of lung adenocarcinomas with differing survival and prognostic features. These results are helpful in defining a subcategory of 'minimally invasive adenocarcinoma', which has features similar to bronchioloalveolar carcinoma.Modern Pathology (2007) 20, 233-241. doi:10.1038/modpathol.3800734; published online 22 December 2006
— id: 71022, year: 2007, vol: 20, page: 233, stat: Journal Article,

Exploring the utility of automated drug alerts in home healthcare
Feldman, Penny Hollander; McDonald, Margaret; Rosati, Robert J; Murtaugh, Christopher; Kovner, Christine; Goldberg, Judith D; King, Lori
2006 Jan-Feb;28(1):29-40, Journal for healthcare quality
Computerized drug utilization review (DUR) can potentially reduce adverse drug events. We examined automated DUR for home healthcare patients with diabetes or hypertension. Sixty-eight percent of diabetes patients and 50.7% of hypertension patients triggered severe, moderate, or duplicative alerts. Among diabetes patients, 74.3% of duplicative alerts were trivial or inappropriate, compared with 3.9% among hypertension patients. Experts judged that 40.5% of high-risk diabetes patients and 53.6% of hypertension patients had alerts requiring nurse follow-up. Adequate follow-up was significantly lower for the former. The relationship between inappropriate alerts and poorer follow-up reinforces the need for more specific alert systems to focus clinicians' attention on clinically important alerts
— id: 71023, year: 2006, vol: 28, page: 29, stat: Journal Article,

Accelerated prone breast radiotherapy: preliminary results of a prospective intensity modulated radiotherapy (IMRT) trial
Formenti, SC; Gidea-Addeo, D; Wernicke, AG; Goldberg, JD; Amber, GA; DeWyngaert, JK
2006 FEB ;100(2):S198-S199, Breast cancer research & treatment
— id: 71010, year: 2006, vol: 100, page: S198, stat: Journal Article,

The changing role of statistics in medical research : experiences from the past and directions for the future. Invited paper
Goldberg, Judith D
2006 ;2006:1963-1969, Proceedings (American Statistical Association)
— id: 71155, year: 2006, vol: 2006, page: 1963, stat: Journal Article,

A translationally controlled angiogenic switch in locally advanced breast cancer
Karpisheva, K; Braunstein, S; Goldberg, J; Singh, B; Pola, C; Formenti, SC; Schneider, RJ
2006 FEB ;100(2):S11-S11, Breast cancer research & treatment
— id: 71005, year: 2006, vol: 100, page: S11, stat: Journal Article,

MTOR/4E-BP1 pathway is a translational regulator of prostate cancer progression
Karpisheva, KV; Xi, QR; Braunstein, S; Melamed, J; Goldberg, J; Schneider, R
2006 MAR 6 ;20(4):A109-A109, FASEB journal
— id: 63857, year: 2006, vol: 20, page: A109, stat: Journal Article,

False discovery rate for statistical designs to test both superiority and non-inferiority in controlled
Mukhi, Vandana; Goldberg, Judith; Shao, Yongzhao
2006 ;:4289-4296, Proceedings (American Statistical Association)
— id: 71028, year: 2006, vol: , page: 4289, stat: Journal Article,

Evaluation of pro-carboxypeptidase A and carboxypeptidase A as serologic markers for adenocarcinoma of the pancreas
Shamamian, Peter; Goldberg, Judith D; Ye, Xiang Y; Stewart, Jonathan D; White, Peter J; Gilvarg, Charles
2006 ;8(6):451-457, HPB : the official journal of the International Hepato Pancreato Biliary Association
Background: A serological marker for pancreatic cancer may allow for early detection and potentially more effective treatments. Pro-carboxypeptidase A (pro-CPA) is produced exclusively in the pancreas and converted to its active form, CPA, in the intestinal lumen. We hypothesized that alterations in serum pro-CPA and/or CPA may be useful as a diagnostic test for pancreatic cancer. Patients and methods: Serum samples obtained from 34 patients with pancreatic adenocarcinoma prior to surgical intervention and 64 control patients were assayed for pro-CPA and CPA. A variety of statistical methods was used to evaluate the utility of these measurements individually and in combination to classify the samples with respect to the presence or absence of pancreatic adenocarcinoma. Results: Because of positive skewing of the data in some populations, transformation of the data to natural logarithmic scales was used and resulted in normal distributions. All pancreatic cancer patients had ln(CPA) levels within or below the normal range defined as two standard deviations from the control group mean (-2.714+/-0.413). Ln(pro-CPA) levels in 24 of 34 cancer patients were outside the normal range of the control group (0.306+/-0.33). Pancreatic cancer patients with ln pro-CPA values within the control range had low ln CPA, advanced stage and/or evidence of pancreatic insufficiency. While each of these individual values (ln pro-CPA or ln CPA) does not adequately separate all control from cancer patients, a bivariate classification rule is presented that uses both ln pro-CPA and ln CPA simultaneously to predict the presence of pancreatic cancer with a sensitivity of 91% and a specificity of 95%. Conclusions: The data presented suggest that abnormalities in serum pro-CPA and CPA levels are associated with the presence of pancreatic cancer
— id: 96470, year: 2006, vol: 8, page: 451, stat: Journal Article,

External beam partial breast irradiation following breast-conserving surgery: Preliminary results of cosmetic outcome of NYU 00-23
Wernicke, AG; Gidea-Addeo, D; Magnolfi, C; Fenton-Kerimian, M; Goldberg, J; Formenti, SC
2006 FEB ;66(3):S32-S32, International journal of radiation oncology biology physics
— id: 70751, year: 2006, vol: 66, page: S32, stat: Journal Article,

Fludrocortisone in patients with familial dysautonomia--assessing effect on clinical parameters and gene expression
Axelrod, Felicia B; Goldberg, Judith D; Rolnitzky, Linda; Mull, James; Mann, Sandra P; Gold von Simson, Gabrielle; Berlin, Dena; Slaugenhaupt, Susan A
2005 Aug;15(4):284-291, Clinical autonomic research
The common familial dysautonomia (FD) mutation causes a splicing defect that leads to production of both wild-type (WT) and mutant (MU) IKBKAP mRNA. Because drugs may alter splicing, seven drugs, fludrocortisone, midodrine, diazepam, albuterol, clonidine, caffeine, and dopamine were screened. Since only fludrocortisone negatively altered gene expression, we assessed fludrocortisone's efficacy in treating postural hypotension, and its effect on survival and secondary long-term FD problems. For 341 FD patients we obtained demographic data and clinical information from the last Center evaluation (most current or prior to death) including mean blood pressures (supine, 1 min erect and 5 min erect) and history regarding syncope and presyncope symptoms. For 175 fludrocortisone-treated patients, data from the evaluation prior to start of fludrocortisone and from the last Center evaluation were compared. The fludrocortisone-treated patient cohort was compared to the nontreated patient cohort with respect to overall survival and event-free survival for crisis frequency, worsening gait, frequent fractures, spine curvature, renal insufficiency, and pacemaker insertion. Overall survivals of patients on fludrocortisone alone, on fludrocortisone and midodrine, and on neither drug were compared. Cumulative survival was significantly higher in fludrocortisone-treated patients than in non-treated patients during the first decade. In subsequent decades, the addition of midodrine improved cumulative survival. Fludrocortisone significantly increased mean blood pressures and decreased dizziness and leg cramping, but not headaches or syncope. Fludrocortisone was associated with more long-term problems, which may reflect more symptomatic status associated with longer survival. Our data suggest that fludrocortisone has clinical efficacy despite negative in vitro observations on gene expression
— id: 58717, year: 2005, vol: 15, page: 284, stat: Journal Article,

Helicobacter pylori and overweight status in the United States: data from the Third National Health and Nutrition Examination Survey
Cho, Ilseung; Blaser, Martin J; Francois, Fritz; Mathew, Jomol P; Ye, Xiang Y; Goldberg, Judith D; Bini, Edmund J
2005 Sep 15;162(6):579-584, American journal of epidemiology
Obesity is an important public health problem in the United States. Because of its potential effects on gastric leptin homeostasis, Helicobacter pylori may play a role in regulating body weight. The authors' aim in this study was to examine the association between H. pylori colonization and overweight status. Nonpregnant participants in the Third National Health and Nutrition Examination Survey (1988-1994) aged > or = 20 years who had had H. pylori testing performed and body mass index (weight (kg)/height (m2)) measured were studied. Overweight was defined as a body mass index greater than or equal to 25. On the basis of serologic results, the participants were categorized into three H. pylori status groups: H. pylori-positive and cytotoxin-associated gene A (cagA)-positive (H. pylori+ cagA+), H. pylori-positive and cagA-negative (H. pylori+ cagA-), and H. pylori-negative (H. pylori-). Of the 7,003 subjects with complete body mass index and H. pylori data, 2,634 (weighted percentage, 22.9%) were H. pylori+ cagA+, 1,385 (15.1%) were H. pylori+ cagA-, and 2,984 (62.0%) were H. pylori-. The adjusted odds of being overweight were 1.17 (95% confidence interval: 0.98, 1.39; p = 0.075) for the H. pylori+ cagA+ group and 0.99 (95% confidence interval: 0.80, 1.22; p = 0.92) for the H. pylori+ cagA- group in comparison with H. pylori- subjects. Serum leptin levels did not differ significantly between the three H. pylori groups. In this US population-based study, there was no significant association between H. pylori colonization, cagA+ strains of H. pylori, and being overweight
— id: 58658, year: 2005, vol: 162, page: 579, stat: Journal Article,

NYU 03-30: Accelerated IMRT with concomitant boost after breast conservation surgery. preliminary clinical results in 70 patients
Formenti, SC; Mitchell, J; Goldberg, J; Magnolfi, C; Rosenstein, B; Remon, S; DeWyngaert, K
2005 ;63(2):S181-S182, International journal of radiation oncology biology physics
— id: 109264, year: 2005, vol: 63, page: S181, stat: Journal Article,

The importance of location in determining breast conservation rates
Hiotis, Karen; Ye, Wei; Sposto, Richard; Goldberg, Judith; Mukhi, Vandana; Skinner, Kristin
2005 Jul;190(1):18-22, American journal of surgery
BACKGROUND: This study evaluates differences in the utilization of breast conservation surgery (BCS) between major metropolitan areas in the United States (US) and the United Kingdom (UK). METHODS: Surgical and staging information were obtained from the Cancer Surveillance Program for Los Angeles County (LAC), the New York State (NYS) Department of Health Cancer Registry, and the UK National Health Service (NHS) Breast Screening Program. Demographic data were obtained from the census databases from the US, UK, Northern Ireland, and Scotland. Descriptive statistics, correlation analysis, and chi-square tests were used to compare rates of BCS across the locations under study. RESULTS: Breast conservation rates were highest in London (79.3%) compared to New York City (NYC) (69.7%) and LAC (66.5%) (P < .0001). Both in NYS and the UK, the cities differ from the surrounding regions in population density, education levels, agricultural activities, and unemployment. BCS rates tended to increase with population density and education levels, and decrease with increased unemployment and agricultural activity, but there was no impact on BCS rates when adjustments for these variables were included in regression models. BCS rates increase with increasing hospital case volume in LAC and NYC (P < .0001). CONCLUSION: When comparing large metropolitan areas in the US and UK there are significantly different rates of BCS in different locations. These differences reflect differences in population density, socioeconomic status (SES), education levels, hospital volume, and the effects of a nationally funded screening program
— id: 71025, year: 2005, vol: 190, page: 18, stat: Journal Article,

Examining nurses' decision process for medication management in home care
Kovner, Christine; Menezes, Joyce; Goldberg, Judith D
2005 Jul;31(7):379-385, Joint Commission journal on quality & patient safety / Joint Commission Resources
BACKGROUND: The process of medication management within home care agencies was prospectively described, with a focus on the nurse's role and critical points in the process. The process the nurse must follow includes preparing, checking, and administering medications; updating knowledge of medications; monitoring the effectiveness of treatment; reporting adverse reactions; and teaching patients about their drugs. PROCESSES FOR MEDICATION MANAGEMENT IN HOME HEALTH CARE: The steps that home health nurses (HHNs) go through with families and the system changes that could be developed to decrease errors were identified. The approach was based on Failure Mode and Effects Analysis-a method to identify and prevent process problems before they occur. The medication management process was divided into drug utilization review (DUR) for duplicative and harmful interactions; drug administration by the patient, family member, and/or caregiver; and side effects. Failure modes were developed for a DUR for duplicative and harmful interactions. DISCUSSION: Home health agencies should analyze the medication management process in their own agencies and identify system solutions. The difficulty encountered by HHNs in contacting physicians to discuss changes to the drug regimen following the assessment of potential drug interactions or duplications is an ongoing problem. Careful monitoring by HHNs could decrease the impact of adverse drug effects
— id: 62534, year: 2005, vol: 31, page: 379, stat: Journal Article,

Quality of life and behavioral follow-up study of pediatric survivors of craniopharyngioma
Sands, Stephen A; Milner, Jessica S; Goldberg, Judith; Mukhi, Vandana; Moliterno, Jennifer A; Maxfield, Carol; Wisoff, Jeffrey H
2005 Oct;103(4 Suppl):302-311, Journal of neurosurgery
OBJECT: The authors set out to evaluate the quality of life (QOL), social-emotional functioning, and behavioral functioning of children treated surgically for craniopharyngiomas. METHODS: Twelve girls and 17 boys with a mean age at diagnosis of 8 +/- 3.8 years were surgically treated between 1985 and 1998 at the New York University Medical Center. After a mean follow-up period of 6.8 +/- 3.5 years, these 29 patients were administered either the 36-item Short Form Health Survey version 2 or the Child Health Questionnaire-Parent Form to assess QOL, as well as the Achenbach Child Behavior Checklist or Young Adult Checklist to measure social-emotional and behavioral functioning. Patients older than 19 years of age and parents of patients younger than 19 years of age reported low average overall physical QOL, with overall psychosocial QOL in the average range. Behavioral difficulties were noted, including internalizing, attention, somatic, and social difficulties. Further analyses indicated that retrochiasmatic tumor location, recurrence, and additional surgery were associated with poorer outcomes. In contrast, hydrocephalus, tumor size, and sex were not prognostic variables, and patients significantly improved as post-operative time increased. CONCLUSIONS: Attention toward late effects arising after the treatment of pediatric craniopharyngioma, including decreased postoperative physical health and behavioral functioning, is warranted. Future approaches to treatment should consider the documented effects of either gross-total resection or limited surgery followed by cranial irradiation on QOL, with specific evaluation for those with retrochiasmatic tumors, a recurrent tumor, or the need for additional surgery. Psychosocial QOL and social-emotional functioning should be maintained through ongoing counseling and education
— id: 71024, year: 2005, vol: 103, page: 302, stat: Journal Article,

The importance of end-systole for optimal reconstruction protocol of coronary angiography with 16-slice multidetector computed tomography
Sanz, Javier; Rius, Teresa; Kuschnir, Paola; Fuster, Valentin; Goldberg, Judith; Ye, Xiang Y; Wisdom, Paul; Poon, Michael
2005 Mar;40(3):155-163, Investigative radiology
OBJECTIVES: Multidetector-row computed tomography coronary images are usually analyzed in mid-diastole (MD). Because of slow coronary motion also in end-systole (ES), we evaluated the impact on image quality of including ES images and defined an efficient reconstruction protocol. MATERIAL AND METHODS: In 50 coronary multidetector-row computed tomography studies, 9 reconstructions (at 10% increments of the RR interval) were graded for image quality. Multiple combinations of reconstructions were compared. RESULTS: MD (60-70% of the RR interval) offered the best image quality. In 44% patients, the best reconstruction for >or=1 coronary was found in ES (20-30%). Their heart rate was higher (68.2+/-9.9 bpm vs. 59.2+/-8.8 bpm, P=0.0014). Combining ES and MD consistently offered superior image quality and less nonevaluable vessels than even larger numbers of diastolic reconstructions alone. A combination of 2-3 reconstructions was most efficient. Adding more reconstructions did not significantly improve results. CONCLUSIONS: Combining ES and MD reconstructions reduces nonevaluable coronary arteries, particularly with higher heart rates. A protocol including 2-3 reconstructions is the most efficient
— id: 71026, year: 2005, vol: 40, page: 155, stat: Journal Article,

Prone accelerated partial breast irradiation (five fractions) after breast conservation therapy with heart and lung sparing
Formenti, SC; Goldberg, J; Rosenstein, B; Dewyngaert, K
2004 ;22(14):93S-93S #870, Journal of clinical oncology
— id: 109269, year: 2004, vol: 22, page: 93S, stat: Journal Article,

Importance of MR technique for stereotactic radiosurgery
Donahue, Bernadine R; Goldberg, Judith D; Golfinos, John G; Knopp, Edmond A; Comiskey, Jessica; Rush, Stephen C; Han, Kerry; Mukhi, Vandana; Cooper, Jay S
2003 Oct;5(4):268-274, Neuro-oncology
We investigated how frequently the imaging procedure we use immediately prior to radiosurgery--triple-dose gadolinium-enhanced MR performed with the patient immobilized in a nonrelocatable head frame and 1-mm-thick MPRAGE (magnetization-prepared rapid gradient echo) images (SRS3xGado)-identifies previously unrecognized cerebral metastases in patients initially imaged by conventional MR with single-dose gadolinium (1xGado). Between July 1998 and July 2000, the diagnoses established for 47 patients who underwent radio-surgical procedures for treatment of cerebral metastases at The Gamma Knife Center of New York University were based initially on the 1xGado protocol. In July 1998, we began using SRS3xGado as our routine imaging protocol in preparation for targeting lesions for radio-surgery, using triple-dose gadolinium and acquisition of contiguous 1-mm Tl-weighted axial images. Because our SRS3xGado scans sometimes unexpectedly revealed additional metastases, we sought to learn how frequently the initial 1xGado scans would underestimate the number of metastases. We therefore reviewed the number of brain metastases identified on the SRS3xGado studies and compared the results to the number found by the 1xGado protocol, which had initially identified the brain metastases. Additional metastases, ranging from 1 to 23 lesions per patient, were identified on the SRS3xGado scan in 23 of 47 patients (49%). In 57% of the 23 patients, only one additional lesion was identified. The mean time interval between the 1xGado and the SRS3xGado scans was 20.6 days (range, 4-83 days), and the number of additional lesions detected and the time interval between two scans were negatively correlated (-0.11). The number of lesions detected on the SRS3xGado was associated only with the number of lesions on the 1xGado and not with any other patient or tumor pretreatment characteristics such as age, gender, largest tumor volume on the 1xGado, or number of days between the 1xGado and the SRS3xGado or prior surgery. The identification of additional lesions with SRS3xGado MR may have implications for patients who are treated with stereotactic radiosurgery alone (without whole-brain irradiation) with single-dose gadolinium imaging, in that unidentified lesions may go untreated. As a result of these findings we continue to use and advocate SRS3xGado scans for radiosurgery
— id: 42023, year: 2003, vol: 5, page: 268, stat: Journal Article,

Optimized schedules of topotecan combined with Y-90 huBrE3 radioinummotherapy show enhanced tumor response in an in vivo ovarian carcinoma model
Kramer, E; Ng, B; Liebes, L; Furmanski, JG; Goldberg, J; Mukhi, V; Ceriani, R; Curtin, J
2003 DEC 1 ;9(16):6190S-6190S, Clinical cancer research
— id: 42541, year: 2003, vol: 9, page: 6190S, stat: Journal Article,

Hypo-fractionated partial breast radiation after breast-conserving surgery: preliminary clinical results and dose volume histogram (DVH) analysis
Truong M; Rosenstein B; Goldberg J; Cho C; DeWyngaert KJ; Formenti SC
2003 Oct 1;57(2 Suppl):S367-S368, International journal of radiation oncology biology physics
— id: 39081, year: 2003, vol: 57, page: S367, stat: Journal Article,

Risk of malignancy in follicular neoplasms without nuclear atypia: statistical analysis of 397 thyroidectomies
Yang, Grace C H; Goldberg, Judith D; Ye, Philip X
2003 Nov-Dec;9(6):510-516, Endocrine practice
Objective: To determine how to triage patients with a follicular neoplasm (FN), without nuclear atypia reported by fine-needle aspiration, on the basis of risk factors. Methods: The age, sex, tumor size, and cell type of 397 patients who underwent thyroidectomy for follicular carcinoma (FC) or follicular adenoma between 1991 and 2001 were analyzed statistically. The likelihood ratio and probability of FC for various combinations of tumor size, sex, and cell type were estimated with use of Bayes' theorem. Results: FC was significantly associated with tumor size >2.1 cm (P = 0.048), male sex (P = 0.0007), and Hurthle cell type (P<0.0001). The mean size of minimally invasive FC was significantly smaller (2.9 cm versus 4.8 cm; P = 0.004) and the mean patient age was significantly younger (47.6 years versus 61.0 years; P = 0.003) than for widely invasive FC. The lowest probability (0.31%) for FC was in female patients with a small ( 2.1 cm) micro-follicular FN reported by a cytopathology practice with 10% accuracy of true FN at surgical intervention, whereas the highest probability (29.5%) for FC was in male patients with a large (>2.1 cm) Hurthle cell neoplasm reported by a cytopathology practice with 70% accuracy of true FN at surgical intervention. Conclusion: Although an estimate of probability for FC based on age, sex, thyroid nodule size, and cell type is provided in this study for patients diagnosed with FN without nuclear atypia on fine-needle aspiration, the variability of the accuracy in cytopathology practice makes it difficult to change the current treatment paradigm, which requires carefully planned prospective studies with long-term follow-up. (Endocr Pract. 2003;9:510-516)
— id: 41651, year: 2003, vol: 9, page: 510, stat: Journal Article,

Survival in familial dysautonomia: Impact of early intervention
Axelrod, Felicia B; Goldberg, Judith D; Ye, Xiang Y; Maayan, Channa
2002 Oct;141(4):518-523, Journal of pediatrics
OBJECTIVE: To assess the effectiveness of advances in supportive centralized care on survival and function in patients with familial dysautonomia (FD). STUDY DESIGN: From September l, 1969 through January 1, 2001. Five hundred fifty-one patients with FD entered the Dysautonomia Center. We divided the group into two cohorts: the first cohort (n = 227) entered until March 1, 1981, and the second cohort (n = 324) entered after March 1, 1981. Survival curves were compared by using log-rank tests. Demographic and disease characteristics were examined, including gender, geographic location, age at entry, birth weight, breath-holding history, age of walking, causes of death, and social data. RESULTS: For both cohorts age at entry was the primary variable that influenced survival; mortality increased by 3% per year. Survival time lengthened for cohort 2 when survival time was defined as time from entry into the Center to last observation or death; in cohort 2, mortality was 73% that of cohort 1 even after adjustment for age at entry. Although survival improved, causes of death were unchanged; sleep deaths and sudden deaths remained frequent. CONCLUSION: Our data indicate that the more recent cohort patients were younger at the time of entry and had improved survival, which suggests that early access to centralized and more advanced treatment appreciably benefits patients with familial dysautonomia
— id: 39450, year: 2002, vol: 141, page: 518, stat: Journal Article,

Lung-specific expression of dominant-negative mutant p53 in transgenic mice increases spontaneous and benzo(a)pyrene-induced lung cancer
Tchou-Wong, Kam-Meng; Jiang, Yixing; Yee, Herman; LaRosa, Jennifer; Lee, Theodore C; Pellicer, Angel; Jagirdar, Jaishree; Gordon, Terry; Goldberg, Judith D; Rom, William N
2002 Aug;27(2):186-193, American journal of respiratory cell & molecular biology
Mutations in the p53 gene have been implicated to play an important role in the development of various human cancers. To evaluate the importance of p53 in lung cancer, a transgenic mouse model was established by utilizing the Clara cell secretory protein (CCSP) promoter to target the expression of a dominant-negative mutant form of p53 (dnp53) in the lung. In two transgenic CCSP-dnp53 founder lines, the dnp53 protein was expressed exclusively in the lungs. The incidence of spontaneous lung cancer in 18-month-old transgenic mice was 45%, whereas that in age-matched control mice was 20%. The relative risk of lung tumors in CCSP-dnp53 mice was 2.3 times that of wild-type mice (exact confidence limits of 0.69, 17.5). In addition to the increased incidence of spontaneous lung tumor, these mice were more susceptible to the development of lung adenocarcinoma after exposure to benzo(a)pyrene (BaP). Six months after intratracheal instillation of benzo(a)pyrene, the tumor incidence in wild-type and CCSP-dnp53 mice was 39% and 73%, respectively. The risk of lung tumors was 25.3 times greater in BaP-treated mice adjusted for transgene expression (95% confidence limits of 3.29, 678, mid-p corrected). These results suggest that p53 function is important for protecting mice from both spontaneous and BaP-induced lung cancers
— id: 32452, year: 2002, vol: 27, page: 186, stat: Journal Article,

Ischemic mitral valve reconstruction and replacement: Comparison of long-term survival and complications
Grossi EA; Goldberg JD; LaPietra A; Ye X; Zakow P; Sussman M; Delianides J; Culliford AT; Esposito RA; Ribakove GH; Galloway AC; Colvin SB
2001 Dec;122(6):1107-1124, Journal of thoracic & cardiovascular surgery
OBJECTIVE: This study reviews the 223 consecutive mitral valve operations for ischemic mitral insufficiency performed at New York University Medical Center between January 1976 and January 1996. The results for mitral valve reconstruction are compared with those for prosthetic mitral valve replacement. METHODS: From January 1976 to January 1996, 223 patients with ischemic mitral insufficiency underwent mitral valve reconstruction (n = 152) or prosthetic mitral valve replacement (n = 71). Coronary artery bypass grafting was performed in 89% of cases of mitral reconstruction and 80% of cases of prosthetic replacement. In the group undergoing reconstruction, 77% had valvuloplasty with a ring annuloplasty and 23% had valvuloplasty with suture annuloplasty. In the group undergoing prosthetic replacement, 82% of patients received bioprostheses and 18% received mechanical prostheses. RESULTS: Follow-up was 93% complete (median 14.6 mo, range 0-219 mo). Thirty-day mortality was 10% for mitral reconstruction and 20% for prosthetic replacement. The short-term mortality was higher among patients in New York Heart Association functional class IV than among those in classes I to III (odds ratio 5.75, confidence interval 1.25-26.5) and was reduced among patients with angina relative to those without angina (odds ratio 0.26, confidence interval 0.05-1.2). The 30-day death or complication rate was similarly elevated among patients in functional class IV (odds ratio 5.53; confidence interval 1.23-25.04). Patients with mitral valve reconstruction had lower short-term complication or death rates than did patients with prosthetic valve replacement (odds ratio 0.43, confidence interval 0.20-0.90). Eighty-two percent of patients with mitral valve reconstruction had no insufficiency or only trace insufficiency during the long-term follow-up period. Five-year complication-free survivals were 64% (confidence interval 54%-74%) for patients undergoing mitral valve reconstruction and 47% (confidence interval 33%-60%) for patients undergoing prosthetic valve replacement. Results of a series of statistical analyses suggest that outcome was linked primarily to preoperative New York Heart Association functional class. CONCLUSIONS: Initial mortalities were similar among patients undergoing prosthetic replacement and valve reconstruction. Poor outcome was primarily related to preexisting comorbidities. Patients undergoing valve reconstruction had fewer valve-related complications. Valve reconstruction resulted in excellent durability and freedom from complications. These findings suggest that mitral valve reconstruction should be considered for appropriate patients with ischemic mitral insufficiency
— id: 24634, year: 2001, vol: 122, page: 1107, stat: Journal Article,

The effects of outcome misclassification and measurement error on the design and analysis of therapeutic equivalence trials
Kim MY; Goldberg JD
2001 Jul 30;20(14):2065-2078, Statistics in medicine
In any clinical trial, the use of imperfect diagnostic procedures or laboratory techniques may lead to misclassification and measurement error in the primary outcome. Although the effects of non-differential outcome misclassification and measurement error on conventional superiority trials have been extensively investigated, less is known about the impact of these errors on the results and interpretation of therapeutic equivalence trials. In this paper we formally investigate the effects of outcome misclassification and measurement error on the estimates of treatment effects, type I error rate, and power of equivalence trials. Our results indicate that, contrary to what one may expect based on the well known attenuating effects of non-differential error in conventional studies, these errors do not always favour the goal of demonstrating equivalence. The magnitude and direction of the influence depend on a number of factors including the nature of the outcome variable, specific formulation of equivalence, size of the error rates, and assumptions regarding the true treatment effect.
— id: 21147, year: 2001, vol: 20, page: 2065, stat: Journal Article,

Anastomotic strictures following radical prostatectomy: insights into incidence, effectiveness of intervention, effect on continence, and factors predisposing to occurrence
Park R; Martin S; Goldberg JD; Lepor H
2001 Apr;57(4):742-746, Urology
OBJECTIVES: To examine the incidence, effectiveness of intervention, effect on continence, and factors predisposing to the occurrence of anastomotic strictures following radical retropubic prostatectomy. METHODS: Between January 1994 and June 1999, 753 radical retropubic prostatectomies were performed by a single surgeon. Anastomotic strictures were managed by dilatation followed by a self-catheterization regimen. Dilatations were repeated unless more than three dilatations were required over a 9-month interval. A control group representing a randomly selected group of men who did not develop anastomotic strictures was identified. The largest width of the midline vertical abdominal scar was measured. RESULTS: Of the 753 radical retropubic prostatectomies, 36 (4.8%) developed an anastomotic stricture. The mean time interval between the surgical procedure and diagnosis of the stricture was 4.22 months. Of the 26 cases of anastomotic strictures with at least 1-year follow-up, 24 (92.3%) were managed successfully by dilatations alone. No baseline characteristics before surgery were associated with the development of a stricture. The maximal scar width was the only factor that was associated with the development of a stricture in this study. Men with a maximal scar of greater than 10 mm were eight times more likely to develop strictures than men with smaller scars. The percentage of men who required protective pads 1 year following radical retropubic prostatectomy in the control and stricture groups was 12.5% and 46.2%, respectively. CONCLUSIONS: Anastomotic strictures are relatively rare following radical prostatectomy and have a negative effect on the development of continence. Most men are successfully managed with dilatations alone. The development of anastomotic strictures in some men appears to be related to a generalized hypertrophic wound-healing mechanism
— id: 21197, year: 2001, vol: 57, page: 742, stat: Journal Article,

Knowledge discovery from databases and data mining: new paradigms for statistics and data analysis
Friedman H; Goldberg JD
2000 ;8(2):1-12, Biopharmaceutical report
— id: 24760, year: 2000, vol: 8, page: 1, stat: Journal Article,

CD4+ T Cell Surface CCR5 Density and Virus Load in Persons Infected with Human Immunodeficiency Virus Type 1
Marmor M; Krowka J; Goldberg JD
2000 Oct;182(4):1284-1285, Journal of infectious diseases
— id: 11507, year: 2000, vol: 182, page: 1284, stat: Journal Article,

Applied survival analysis / by Chap T. Le
Goldberg JD
1999 ;40:267-268, Technometrics
— id: 24759, year: 1999, vol: 40, page: 267, stat: Journal Article,

Meta-analysis: an introduction and point of view
Friedman HP; Goldberg JD
1996 Apr;23(4):917-928, Hepatology
— id: 24671, year: 1996, vol: 23, page: 917, stat: Journal Article,

Treatment of Polycythemia Vera : a summary of clinical trails conducted by the Polycythemia Vera Study Group
Berk JD; Wasserman LR; Fruchtman SM; Goldberg JD
Polycythemia Vera and the myeloproliferative disorders Philadelphia : WB Saunders, 1995,
— id: 2651, year: 1995, vol: , page: 166, stat: Chapter,

A multifactorial trial design to assess combination therapy in hypertension. Treatment with bisoprolol and hydrochlorothiazide
Frishman WH; Bryzinski BS; Coulson LR; DeQuattro VL; Vlachakis ND; Mroczek WJ; Dukart G; Goldberg JD; Alemayehu D; Koury K
1994 Jul 11;154(13):1461-1468, Archives of internal medicine
BACKGROUND: The safety and effectiveness of different dosages and combinations of antihypertensive agents can be efficiently studied using a multifactorial trial design. In consultation with the Cardio-Renal Division of the Food and Drug Administration, we conducted a randomized, double-blind, placebo-controlled, 3 x 4 factorial trial of bisoprolol, a beta 1-selective adrenergic blocking agent, and hydrochlorothiazide. METHODS: A total of 512 patients with mild to moderate essential hypertension were randomized to once-daily treatment with bisoprolol (0, 2.5, 10, or 40 mg), hydrochlorothiazide (0, 6.25, or 25 mg), and all possible combinations. Diastolic and systolic blood pressures were monitored during this 12-week trial. RESULTS: The effects of bisoprolol and hydrochlorothiazide were additive with respect to reductions in diastolic and systolic blood pressures over the dosage ranges studied. The addition of hydrochlorothiazide (or bisoprolol) to therapy with bisoprolol (or hydrochlorothiazide) produced an incremental reduction in blood pressure. Dosages of hydrochlorothiazide as low as 6.25 mg/d contributed a significant antihypertensive effect. A hydrochlorothiazide dosage of 6.25 mg/d produced significantly less hypokalemia and less of an increase in uric acid levels than a dosage of 25 mg/d. The low-dose combination of bisoprolol, 2.5 mg/d, and hydrochlorothiazide, 6.25 mg/d, reduced diastolic blood pressure to lower than 90 mm Hg in 61% of patients and demonstrated a safety profile that compared favorably with that of placebo. CONCLUSIONS: The utility of factorial design trials to characterize dose-response relationships and to test the potential interactions between various antihypertensive agents has been demonstrated. The combination of low dosages of bisoprolol and hydrochlorothiazide may be a rational alternative to conventional stepped-care therapy for the initial treatment of patients with mild to moderate hypertension
— id: 24635, year: 1994, vol: 154, page: 1461, stat: Journal Article,

Toward strategies for the analysis of periodontal disease clinical trials
Alemayehu D; Goldberg JD; Koury KJ
1992 Jul;27(4 Pt 2):342-346, Journal of periodontal research
We consider design, analysis and regulatory issues relating to clinical trials in periodontal disease and identify complications commonly associated with such studies. Alternative statistical procedures that can be used for the analyses of data from periodontal research are reviewed and a case study of the analysis of a Phase II periodontal disease clinical trial is provided to illustrate the use of one of these procedures
— id: 24636, year: 1992, vol: 27, page: 342, stat: Journal Article,

Design and analysis of multicenter trials
Goldberg JD; Koury KJ
Statistical methodology in the pharmaceutical sciences New York : Dekker, 1990,
— id: 2657, year: 1990, vol: , page: 201, stat: Chapter,

Charcoal hemoperfusion. Plus ca change, plus c'est la meme chose
Berk PD; Goldberg JD
1988 May;94(5 Pt 1):1228-1230, Gastroenterology
— id: 24637, year: 1988, vol: 94, page: 1228, stat: Journal Article,

"The statistical precision of medical screening procedures: applications to polygraph and AIDS antibodies tesst date" / J. Gastwirth [Invited Comment]
Goldberg JD
1987 ;2:230-231, Statistical science
— id: 24758, year: 1987, vol: 2, page: 230, stat: Journal Article,

Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols
Berk PD; Goldberg JD; Donovan PB; Fruchtman SM; Berlin NI; Wasserman LR
1986 Apr;23(2):132-143, Seminars in hematology
The PVSG was organized in 1967 to establish effective diagnostic criteria for polycythemia vera, to study the natural history of the disease and to define the optimal treatment. Although polycythemia vera and the other myeloproliferative diseases are relatively uncommon, the PVSG was able to accumulate well over 1,000 patients with these various disorders and to study them according to a total of 15 different protocols. PVSG-01, a long-term randomized controlled study of phlebotomy alone compared with the myelosuppressive agents, 32P or chlorambucil supplemented by phlebotomy, continues to receive follow-up data on 93% of surviving patients 18 years after initiation of the study. During its lifetime, PVSG has developed a widely accepted and highly effective set of criteria for the specific diagnosis of polycythemia vera as well as useful criteria for the diagnosis of essential thrombocythemia. It has gathered an enormous volume of data on the natural history of the myeloproliferative diseases and in particular on the nature of the prevalent complications, such as thrombotic events and hematologic and nonhematologic malignancies. With respect to the final question, the optimal treatment for polycythemia vera, it is apparent that the expectation of a single optimal therapy that would apply to all patients at all ages and stages of the disease was naive. Nevertheless considerable progress has been made. Moreover, the group has defined more precisely than ever before the nature of the complications of the disease and the association of the risks of specific complications with specific forms of therapy. It thus has made it possible to pose the next series of therapeutic questions that must be addressed in this disorder with a greater degree of sophistication than was previously possible
— id: 24641, year: 1986, vol: 23, page: 132, stat: Journal Article,

Design of clinical trials for chronic diseases: implications for periodontal disease
Goldberg JD; Weiss AI; Koury KJ
1986 May;13(5):411-417, Journal of clinical periodontology
In order to make effective use of the statistical theory of design of clinical trials for chronic diseases such as periodontal disease, certain issues must be considered. Any clinical trial requires that the disease definition be well-specified; that patient eligibility be explicit; that the observation times be explicit; that the duration and endpoint of therapy be specified; that the duration of subsequent followup observation be specified; and that the unit of observation (e.g., tooth, set of teeth, patient) be defined. In a chronic disease, the potential biases that can readily be introduced by self-selection of patients who enter the trial and/or who return for subsequent observation become more important, because subjects are required to remain on treatment and/or observation for prolonged periods. Further, the cyclical nature of some chronic diseases may require special attention to baseline definitions of active disease and disease outcome. These issues are illustrated with examples from clinical trials of hypertension, breast cancer screening, and Polycythemia Vera. Implications for periodontal disease are discussed
— id: 24640, year: 1986, vol: 13, page: 411, stat: Journal Article,

Long-term management of polycythemia vera with hydroxyurea: a progress report
Kaplan ME; Mack K; Goldberg JD; Donovan PB; Berk PD; Wasserman LR
1986 Jul;23(3):167-171, Seminars in hematology
— id: 24639, year: 1986, vol: 23, page: 167, stat: Journal Article,

Adverse effects of antiaggregating platelet therapy in the treatment of polycythemia vera
Tartaglia AP; Goldberg JD; Berk PD; Wasserman LR
1986 Jul;23(3):172-176, Seminars in hematology
— id: 24638, year: 1986, vol: 23, page: 172, stat: Journal Article,

A study of liver biopsies and liver disease among hemophiliacs
Aledort LM; Levine PH; Hilgartner M; Blatt P; Spero JA; Goldberg JD; Bianchi L; Desmet V; Scheuer P; Popper H; et al.
1985 Aug;66(2):367-372, Blood
Hepatic histologic materials (biopsy or autopsy) and associated clinical data from 155 hemophiliacs were collected by an ad hoc hemophilia study group and analyzed retrospectively in an effort to determine the spectrum of liver disease in this population and to examine the relationship between the severity of liver disease and treatment history. Clinical information on the frequency of complications from 126 biopsies in 115 hemophilic patients provided a unique opportunity to assess the safety of liver biopsy in such patients. The incidence of cirrhosis (15%) and chronic active hepatitis (7%) was lower than previously reported. The frequency of severe liver disease (chronic active hepatitis or cirrhosis) in patients receiving large pooled concentrates was no greater than in patients treated principally with cryoprecipitate or plasma. The risks of liver biopsy in this setting are relatively high: clinically significant hemorrhage followed 12.5% of the procedures
— id: 24642, year: 1985, vol: 66, page: 367, stat: Journal Article,

Mitoxantrone: an overview of safety and toxicity
Posner LE; Dukart G; Goldberg J; Bernstein T; Cartwright K
1985 ;3(2):123-132, Investigational new drugs
Mitoxantrone (Novantrone), is an anthracenedione which in preclinical studies demonstrated a spectrum of antitumor activity similar to the anthracyclines, but with less cardiotoxicity. Novantrone is a cytotoxic agent that produces dose-dependent myelosuppression. When administered to patients intravenously every three weeks, white blood cell (WBC) and platelet nadirs occurred between days 8 and 15 with hematologic recovery by day 22. In multiple clinical trials in over 4450 patients, including 372 patients in randomized trials against Adriamycin, Novantrone was consistently associated with a reduced incidence of moderate and severe acute side-effects. In four randomized trials the adverse experience profile associated with Novantrone was superior to that of Adriamycin with statistically significant lower incidences of mucositis/stomatitis, nausea, vomiting and alopecia. Novantrone was less cardiotoxic than Adriamycin and cardiac events were rare in patients without predisposing risk factors. The high level of activity combined with improved patient tolerance and decreased toxicity make Novantrone a promising agent for patients requiring cytotoxic chemotherapy
— id: 24679, year: 1985, vol: 3, page: 123, stat: Journal Article,

Increased prevalence of polycythemia vera in parents of patients on polycythemia vera study group protocols
Brubaker LH; Wasserman LR; Goldberg JD; Pisciotta AV; McIntyre OR; Kaplan ME; Modan B; Flannery J; Harp R
1984 May;16(4):367-373, American journal of hematology
An investigation of relatives of 652 patients entered on studies of the Polycythemia Vera Study Group yielded five documented cases of the disease among the parents of patients. When compared with expected values based on the Connecticut Tumor Registry and other population studies a significant increase was found in the lifetime incidence of polycythemia vera in parents of these patients
— id: 24644, year: 1984, vol: 16, page: 367, stat: Journal Article,

Treatment of polycythemia vera with hydroxyurea
Donovan PB; Kaplan ME; Goldberg JD; Tatarsky I; Najean Y; Silberstein EB; Knospe WH; Laszlo J; Mack K; Berk PD; et al.
1984 ;17(4):329-334, American journal of hematology
Conventional treatment of polycythemia vera (PV) with radioactive phosphorus or alkylating agents is associated with a significant excess of acute leukemia and cancer of the gastrointestinal tract and skin. There is thus a need for a nonmutagenic agent in the treatment of this disorder. Hydroxyurea (HU) was administered to 118 patients with a loading dose of 30 mg/kg/day for 1 week, which was then reduced to 15 mg/kg/day. Initial control of the elevated hematocrit and platelet count was achieved within 12 weeks in over 80% of patients. Long-term disease control was defined and the accumulative 1-year failure-free survival was 73% in the previously untreated patients and 59% in those patients previously treated with other myelosuppressive modalities. The HU was well tolerated and cytopenia, which generally occurred within the first 8 weeks of therapy, was transient and of little clinical significance. However, it is recommended because of this toxicity that HU be administered initially at a dose of 15-20 mg/kg/day. Three patients developed acute leukemia; two were untreated and one had had myelosuppressive therapy. Hydroxyurea is an effective agent in the treatment of PV, but continued assessment of its mutagenic potential is necessary
— id: 24645, year: 1984, vol: 17, page: 329, stat: Journal Article,

Psychosocial influences on mortality after myocardial infarction
Ruberman W; Weinblatt E; Goldberg JD; Chaudhary BS
1984 Aug 30;311(9):552-559, New England journal of medicine
Psychosocial interviews with 2320 male survivors of acute myocardial infarction, participants in the beta-Blocker Heart Attack Trial, permitted the definition of two variables strongly associated with an increased three-year mortality risk. With other important prognostic factors controlled for, the patients classified as being socially isolated and having a high degree of life stress had more than four times the risk of death of the men with low levels of both stress and isolation. An inverse association of education with mortality in this population reflected the gradient in the prevalence of the defined psychosocial characteristics. High levels of stress and social isolation were most prevalent among the least-educated men and least prevalent among the best-educated. The increase in risk associated with stress and social isolation applied both to total deaths and to sudden cardiac deaths and was noted among men with both high and low levels of ventricular ectopy during hospitalization for the acute infarction
— id: 24643, year: 1984, vol: 311, page: 552, stat: Journal Article,

Effect of intracarotid etoposide on opening the blood-brain barrier
Spigelman MK; Zappulla RA; Goldberg JD; Goldsmith SJ; Marotta D; Malis LI; Holland JF
1984 Summer;1(3):207-211, Cancer drug delivery
The effect of an intracarotid artery infusion of etoposide on blood-brain barrier (BBB) integrity was investigated in a rat model system. The external carotid arteries of Sprague-Dawley rats were catheterized in a retrograde manner. Etoposide in a dose range from 3.0 mg/kg to 22.5 mg/kg was infused into the internal carotid artery by this technique. BBB disruption was evaluated qualitatively by the appearance in the infused hemisphere of the systemically administered dye Evans blue and quantitatively by the ratio of counts of the technetium-labeled chelate of diethylenetriaminepentaacetic acid (99mTc-DTPA) in the infused to the noninfused hemisphere. Evidence of increased BBB permeability was seen at all doses of etoposide. Degree of BBB disruption increased with increasing doses of etoposide. The intracarotid infusion and subsequent BBB disruption were well tolerated. Further clinical trials employing the intracarotid administration of etoposide should be cognizant of the potential for BBB disruption
— id: 24646, year: 1984, vol: 1, page: 207, stat: Journal Article,

Evidence for a clonal model hemoglobin switching
Alter BP; Weinberg RS; Goldberg JD; Jackson BT; Piasecki GJ; Lipton JM; Nathan DG
Globin gene expression and hematopietic differentiation New York : AR Liss, 1983,
— id: 2650, year: 1983, vol: , page: 431, stat: Chapter,

Randomized controlled trial of quinacrine for the treatment of HBsAg-positive chronic hepatitis
Bodenheimer HC Jr; Schaffner F; Vernace S; Hirschman SZ; Goldberg JD; Chalmers T
1983 Nov-Dec;3(6):936-938, Hepatology
Several drugs which react with DNA decrease hepatitis B viral (HBV) DNA polymerase activity in vitro. Because such an alteration of viral replication, if produced in patients with hepatitis B surface antigen (HBsAg)-positive chronic hepatitis, may lead to elimination of viral infection, we conducted a controlled trial of the use of the intercalating agent, quinacrine hydrochloride, in treatment of HBsAg-positive chronic hepatitis. No patient converted from HBsAg positive to negative during the trial and no consistent effect on HBV DNA polymerase activity was noted. Following treatment, elevated transaminase values and alterations of HBV markers were observed in several patients. Fluctuations of transaminase values and HBV markers may reflect alterations in host immunity and viral replication. Quinacrine alone is ineffective in therapy of chronic HBV infection. Additional study with intercalating agents, perhaps in conjunction with other drugs, is suggested
— id: 24648, year: 1983, vol: 3, page: 936, stat: Journal Article,

Cisplatin regimens and improved prognosis of patients with poorly differentiated ovarian cancer
Bruckner HW; Cohen CJ; Goldberg JD; Kabakow B; Wallach RC; Deppe G; Reisman AZ; Gusberg SB; Holland JF
1983 Mar 15;145(6):653-658, American journal of obstetrics & gynecology
Patients with advanced ovarian carcinoma, Stage III or IV (International Federation of Gynaecology and Obstetrics), were randomized to primary chemotherapy with doxorubicin (Adriamycin) and cisplatin plus or minus hexamethylmelamine, and cyclophosphamide (CHAP). The four-drug CHAP regimen produced a 57% complete clinical response rate and a 26% partial response rate for clinically evaluable patients. The median survival of CHAP patients is 25 months. The two-drug Adriamycin-cisplatin (AP) regimen produced a 43% complete response rate and a 35% partial response rate. The median survival is 18 months. The four-drug regimen produced a significantly longer median survival (28 versus 18 months) for patients with poorly differentiated tumors than for patients with well-differentiated tumors on either treatment. Examination of treatment failure or death by treatment, histology, and size of largest residual tumor and comparison to similar patients treated with AP in this and two preceding controlled trials also suggest that CHAP is superior to AP for patients with poorly differentiated tumors
— id: 24684, year: 1983, vol: 145, page: 653, stat: Journal Article,

Phase II trial of combination chemotherapy for pancreatic cancer with 5-fluorouracil, mitomycin C, and hexamethylmelamine
Bruckner HW; Storch JA; Brown JC; Goldberg J; Chamberlin K
1983 ;40(3):165-169, Oncology (New York)
A combination consisting of hexamethylmelamine 150 mg/m2 D2-15, mitomycin C 10 mg/m2 D2 and 5-fluorouracil 30 mg/kg/day as a continuous infusion for 5 days, in 4-5 week cycles, underwent phase II trial as primary therapy for 21 patients with regional and metastatic cancer of the pancreas. Median survival from the onset of therapy was 43 weeks. There were 2 complete responses, 4 minor responses and 6 stable diseases for more than 6 months. Nonambulatory patients were among the responders. There was only 1 life-threatening toxicity (thrombocytopenia) and only 33% of patients had clinically silent severe hematological toxicity. The regimen is well tolerated, active and associated with excellent survival. This regimen is suitable for further confirmatory trials
— id: 24681, year: 1983, vol: 40, page: 165, stat: Journal Article,

Phase II trial of combination chemotherapy of colonic cancer with 5-fluorouracil, mitomycin C, and hexamethylmelamine
Bruckner HW; Storch JA; Brown JC; Goldberg J; Chamberlin K
1983 ;40(3):161-164, Oncology (New York)
HexMF consists of hexamethylmelamine 150 mg/m2 D2-15, mitomycin C (MMC) 10 mg/m2 D2 and 5-fluorouracil (5-FU) 30 mg/kg/day as a continuous infusion D1-5 in 4-5 week cycles. It was designed as an alternative to treating patients with standard single agents in sequence, thereby preventing the testing of new drugs as part of primary therapy. Median survival was 12+ months for patients with measurable and 18+ months for patients with nonmeasurable colorectal cancer. It was 9+ months from the onset of secondary chemotherapy. Toxicity included severe thrombocytopenia (50%), severe leukopenia (25%), and moderate stomatitis (50%). Only one instance of leukopenia was life-threatening. The MMC and 5-FU infusion skeleton provides an attractive strategy for testing new drugs as primary therapy. HexMF itself has a potentially broad antitumor spectrum and excellent acceptance by patients. It is suitable for additional phase II trials
— id: 24680, year: 1983, vol: 40, page: 161, stat: Journal Article,

Carcinoma of the breast: interrelationships among histopathologic features, estrogen receptor activity, and age of the patient
Chabon AB; Goldberg JD; Venet L
1983 Apr;14(4):368-372, Human pathology
Of 398 cases of breast cancer, 350 included data for all of the following: patient age, tumor size, histologic type, presence or absence of lymph node metastasis, nuclear grade of the cancer cells, extent of lymphocytic infiltration around these cells, and estrogen receptor status of the neoplastic tissue. This series is representative of and comparable with those reported in other studies of breast carcinoma. Initial evaluation suggested a relationship of cytologic differentiation and lymphocytic infiltration to estrogen receptor activity. More extensive statistical analyses, however, demonstrated that three factor interrelationships best explain the data concerning nuclear grade, lymphocytic infiltration, and estrogen receptor activity of the tumors in this study. Thus, the results of this investigation serve to warn against inferential judgments based on limited data or restricted evaluation. In addition, the analyses call attention to a significant association between age and lymphocytic infiltration around the tumor cells
— id: 24653, year: 1983, vol: 14, page: 368, stat: Journal Article,

Improved therapy with cisplatin regimens for patients with ovarian carcinoma (FIGO Stages III and IV) as measured by surgical end-staging (second-look operation)
Cohen CJ; Goldberg JD; Holland JF; Bruckner HW; Deppe G; Gusberg SB; Wallach RC; Kabakow B; Rodin J
1983 Apr 15;145(8):955-967, American journal of obstetrics & gynecology
Between 1974 and 1982, 273 patients with epithelial cancer of the ovary (International Federation of Gynaecology and Obstetrics Stages III and IV) were randomized in four therapeutic trials. In Trial I Adriamycin plus cisplatin versus cisplatin alone versus thiotepa plus methotrexate was tested. The superiority of Adriamycin plus cisplatin in producing the best response rate led to its use as the reference arm in subsequent trials. All investigational arms included cisplatin plus other drugs (cyclophosphamide, Adriamycin, hexamethylmelamine, and thiotepa) in various combinations. Eligibility for second look required complete clinical remission and completion of at least 10 cycles of chemotherapy. To date, 73 second-look operations have been performed on randomized patients. An additional 43 nonrandomized patients underwent second-look procedures and are analyzed separately. Between 40% and 46% of patients treated with cisplatin regimens had no disease at second look. Cell differentiation and volume of postoperative disease did not influence response
— id: 24652, year: 1983, vol: 145, page: 955, stat: Journal Article,

Improved therapy with cisplatin regimens for patients with ovarian carcinoma (FIGO III and IV) as measured by surgical end-staging (second-look surgery)--the mount sinai experience
Cohen, C J; Bruckner, H W; Goldberg, J D; Holland, J F
1983 Aug;10(2):307-324, Clinics in obstetrics & gynecology
— id: 133518, year: 1983, vol: 10, page: 307, stat: Journal Article,

Pretreatment marrow cytogenetic status: a predictor of response to remission induction therapy in acute myelogenous leukemia
Conjalka MS; Cuttner J; Wisniewski L; Goldberg JD; Reisman A; Elliott R; Desnick R; Holland JF; Berk PD
1983 May-Jun;50(3):201-207, Mount Sinai journal of medicine
— id: 24651, year: 1983, vol: 50, page: 201, stat: Journal Article,

Increased serum procollagen III aminoterminal peptide in myelofibrosis
Hochweiss S; Fruchtman S; Hahn EG; Gilbert H; Donovan PB; Johnson J; Goldberg JD; Berk PD
1983 Dec;15(4):343-351, American journal of hematology
Myelofibrosis has been shown to involve an increase in type III collagen in the marrow. The aminoterminal procollagen III (PC III) peptide fragment is released during the production of PC III by fibroblasts and its serum level is therefore a marker for type III collagen synthesis. Using a recently developed sensitive radioimmunoassay, serum levels of PC III peptide were measured in 30 patients with myeloproliferative disease and 23 normal volunteers. Levels were found to be elevated above normal values in patients with polycythemia vera, even more elevated in patients with polycythemia and evidence of secondary myelofibrosis with myeloid metaplasia, and most strikingly elevated in patients with agnogenic myeloid metaplasia and severe marrow fibrosis. There was a significant association between serum levels of PC III peptide and the extent of reticulin fibrosis in bone marrow biopsies. Serum PC III level appears to be a quantitative marker for myelofibrosis
— id: 24647, year: 1983, vol: 15, page: 343, stat: Journal Article,

Corticotropin versus hydrocortisone in the intravenous treatment of ulcerative colitis. A prospective, randomized, double-blind clinical trial
Meyers S; Sachar DB; Goldberg JD; Janowitz HD
1983 Aug;85(2):351-357, Gastroenterology
Sixty-six patients hospitalized for ulcerative colitis were treated in a prospective, double-blind, clinical trial. They received either 120 U/day of intravenous corticotropin or 300 mg/day of intravenous hydrocortisone. Patients were randomized within strata defined by whether they had received oral corticosteroids continuously for at least 30 days before the study (group A, 35 patients), or whether they had received no such prior treatment (group B, 31 patients). Twenty-eight of the 66 patients (42%) achieved remission. In group B, the proportion of patients entering remission was greater with corticotropin than with hydrocortisone (63% vs. 27%, 0.025 less than p less than 0.05). The opposite trend was observed within group A, for whom hydrocortisone appeared more effective (53% vs. 25%, 0.05 less than p less than 0.10). Impaired adrenal responsiveness, as measured by serum cortisol and dehydroepiandosterone-sulfate levels, did not explain the different responses to therapy within the two study groups. Twenty of 28 patients whose acute therapy was successful were still in remission 1 yr after study. These data suggest that, at the doses used, intravenous corticotropin therapy of severe ulcerative colitis is the more effective choice for those patients not previously treated with corticosteroids, while intravenous hydrocortisone seems preferable for patients already receiving steroid treatment
— id: 24649, year: 1983, vol: 85, page: 351, stat: Journal Article,

Education, psychosocial stress and sudden cardiac death
Ruberman W; Weinblatt E; Goldberg JD; Chaudhary BS
1983 ;36(2):151-160, Journal of chronic diseases
To explore the hypothesis that low education, associated with high 5-yr sudden-death risk among myocardial infarction survivors demonstrating ventricular arrhythmia, might be a marker for relatively high levels of psychosocial stress, we did telephone interviews with the patients' wives. Analysis of the information obtained on life circumstances and personality attributes resulted in four psychosocial factors that were found to be independent of the patients' educational level. The difference in sudden-death risk in relation to education, given the presence of complex ventricular premature beats in one hour of ECG monitoring, was large and could not be accounted for in multivariate analyses by one or more of these psychosocial factors. Nevertheless, life-table analyses in relation to categorized levels of scores for some of the factors did suggest some modest influences on risk of sudden cardiac death, with severity of disease controlled
— id: 24655, year: 1983, vol: 36, page: 151, stat: Journal Article,

Risk factors for postoperative recurrence of Crohn's disease
Sachar DB; Wolfson DM; Greenstein AJ; Goldberg J; Styczynski R; Janowitz HD
1983 Oct;85(4):917-921, Gastroenterology
To identify potential risk factors that influence postoperative recurrence rates of Crohn's disease, the postoperative recurrence-free survival of 93 patients who underwent their first resections at The Mount Sinai Hospital between 1964 and 1973 has been examined. Features analyzed individually and jointly were age, sex, anatomic location, operative procedure, and preoperative disease duration. In patients with Crohn's colitis, recurrence rates appeared somewhat lower among 11 patients with ileostomy than among 5 patients with anastomosis. In the entire series, recurrence rates were lowest in patients with longest preoperative durations (p = 0.02). This same tendency was especially marked among the 68 patients without ileostomies (p = 0.005). Likewise, among the 38 patients with ileitis, the relative risk of recurrence was significantly lower for those with disease duration exceeding 10 yr (p = 0.01). Relative risk of recurrence in the entire series for patients with 2-yr duration was 1.5 compared with those who had 10-yr duration. This inverse association between preoperative disease duration and postoperative recurrence rate may reflect persisting differences between inherently more aggressive versus more indolent forms of Crohn's disease
— id: 24682, year: 1983, vol: 85, page: 917, stat: Journal Article,

Intracarotid dehydrocholate infusion: a new method for prolonged reversible blood-brain barrier disruption
Spigelman MK; Zappulla RA; Malis LI; Holland JF; Goldsmith SJ; Goldberg JD
1983 Jun;12(6):606-612, Neurosurgery
An animal model for prolonged reversible blood-brain barrier (BBB) disruption has been developed. The external carotid arteries of Osborn-Mendel rats were catheterized in a retrograde manner. Varying concentrations of sodium dehydrocholate were infused into the internal carotid artery by this technique. BBB disruption was evaluated qualitatively by the appearance in the infused hemisphere of the systemically administered dyes Evans blue and sodium fluorescein and quantitatively by the ratio of counts of the technetium-labeled chelate of diethylenetriaminepentaacetic acid (99mTc-DTPA) in the infused to the noninfused hemisphere. The ability of sodium dehydrocholate to disrupt the BBB was documented with all three markers. As the concentration of the infused dehydrocholate was increased, both the incidence and the degree of BBB disruption increased. Reversibility of BBB disruption was evaluated by the administration of sodium fluorescein and 99mTc-DTPA at varying times after BBB disruption. Depending on the concentration of the infused sodium dehydrocholate, altered BBB permeability can be maintained for over 3 days. This new model of prolonged reversible BBB disruption deserves further investigation both for basic studies of the BBB and for therapeutic studies of drug delivery into the central nervous system
— id: 24650, year: 1983, vol: 12, page: 606, stat: Journal Article,

Switch from fetal to adult hemoglobin is associated with a change in progenitor cell population
Weinberg RS; Goldberg JD; Schofield JM; Lenes AL; Styczynski R; Alter BP
1983 Apr;71(4):785-794, Journal of clinical investigation
To examine the switch from fetal to adult hemoglobin at the cellular level, erythroid progenitor cells from newborn infants and adults were cultured in methyl cellulose with erythropoietin. Individual erythroid colonies were labeled with [3H]leucine at various times, and globin synthesis patterns examined by gel electrophoresis and fluorography. The percent gamma- or beta-globin synthesis was determined from the total of gamma + beta, and the percent G gamma from the total of G gamma + A gamma. The nonparametric correlation coefficients of percent G gamma with percent gamma or beta were obtained. Each group of colonies at each time point was examined separately. In colonies from adult blood, the proportion of G gamma-synthesis did not correlate with the proportion of gamma-synthesis. Colonies from newborn blood fell into two groups. Those that developed from relatively mature progenitor cells, and were seen on day 14, showed a strong negative correlation of G gamma with beta-globin synthesis. However, those newborn colonies that developed from immature progenitors, and were seen later in culture (days 17 and 21), showed no correlation of G gamma with beta-synthesis. These findings are compatible with a clonal model for hemoglobin switching. Fetal progenitors, in which G gamma- and beta-syntheses are negatively correlated, are gradually replaced during ontogeny by adult progenitors. The adult progenitors produce more beta (less gamma), and the proportions of G gamma- and gamma- or beta-synthesis are not correlated
— id: 24654, year: 1983, vol: 71, page: 785, stat: Journal Article,

Treatment of anemia in myeloproliferative disorders: a randomized study of fluoxymesterone v transfusions only
Brubaker LH; Briere J; Laszlo J; Kraut E; Landaw SA; Peterson P; Goldberg J; Donovan P
1982 Aug;142(8):1533-1537, Archives of internal medicine
Previously untreated patients who had anemia (hemoglobin level, less than or equal to 10 g/dL) caused by myelofibrosis (MF) (16 patients) or other myeloproliferative disorders (13 patients) were given the opportunity to participate in a prospective randomized study-to be treated either with 30 mg/day of oral fluoxymesterone and necessary transfusions or by transfusions alone. Of the 24 patients whose data could be evaluated, four (29%) of 14 responded well to fluoxymesterone therapy (hemoglobin level rise, of greater than 2 to greater than 10 g/dL and relief of symptoms of anemia), whereas, in the transfusion arm, there were no good 'responders'; one of ten patients was a partial 'remitter' (responder), with a rise in the hemoglobin level of 1 to 2 g/dL. All responders to fluoxymesterone therapy showed a 50% or more maximum uptake of injected ferrous citrate Fe 59 into RBC hemoglobin, whereas no nonresponder met this criterion. All responders had MF (marrow more than one third replaced by collagen). There was no significant difference in survival of patients in the two arms of the study
— id: 24686, year: 1982, vol: 142, page: 1533, stat: Journal Article,

Chemotherapy versus chemoimmunotherapy with levamisole or Corynebacterium parvum in advanced lung cancer
Chahinian AP; Goldberg J; Holland JF; Reisman A; Jaffrey IS; Mandel EM
1982 Jun;66(6):1291-1297, Cancer treatment reports
A total of 109 patients with advanced lung cancer, all cell types, were randomized between MACC chemotherapy only, consisting of methotrexate, doxorubicin (Adriamycin), cyclophosphamide, and lomustine (CCNU); MACC plus levamisole (LMS) orally; and MACC plus Corynebacterium parvum (CP) sc. Of these patients, 101 were evaluable, with no differences among the three treatment groups for overall response rate and survival time. Objective response rates and median survival times were 41% and 230 days for patients given MACC only, 39% and 257 days for those given MACC plus LMS, and 44% and 223 days for those given MACC plus CP, respectively. There was a significant increase in survival for patients with large cell anaplastic carcinoma receiving CP or LMS, particularly in the good-performance-status category. Pretreatment delayed cutaneous hypersensitivity to recall antigens in 50 patients had prognostic significance, but repeat tests after 2 months of treatment in 30 patients did not show different patterns of conversion among the three groups. There was no difference in hematologic toxicity among the three groups. With the possible exception of large cell anaplastic carcinoma, immunotherapy with LMS or CP as given in this trial does not appear to be therapeutically advantageous in advanced lung cancer
— id: 24685, year: 1982, vol: 66, page: 1291, stat: Journal Article,

Role of opsonins in clinical response to granulocyte transfusion in granulocytopenic patients
Keusch GT; Ambinder EP; Kovacs I; Goldberg JD; Phillips DM; Holland JF
1982 Oct;73(4):552-563, American journal of medicine
Fifty febrile severely granulocytopenic patients were given four daily transfusions of 2.2 X 10(10) normal donor granulocytes. Twenty-three (46 percent) responded clinically, although both responders and nonresponders were similar in clinical characteristics at the outset. This study examines the relation between serum opsonic activity before initiation of granulocyte administration and clinical response. Opsonic activity to three test organisms (Escherichia coli 286 and ON 2, and Staphylococcus aureus) and to 15 blood stream isolates from 14 patients was measured as serum-dependent uptake of heat-killed 14C-labeled bacteria by normal donor leukopheresis granulocytes in an in vitro assay and compared with results obtained with a standard normal serum in each assay. At a concentration of 8 percent serum, all patient groups were equivalent to standard (90 to 102 percent) for the three test organisms. When rate-limiting concentrations of serum (1 to 2 percent) were employed, opsonic activity remained similar to standard for S. aureus in all patient groups and for the two E. coli strains in responders (82 to 98 percent). In contrast, opsonins for E. coli decreased to 41 to 50 percent of standard in nonresponders (p less than 0.01). When patients with proved infection were separately analyzed, opsonin activity for E. coli 286 and ON 2 was significantly greater in responders than nonresponders (73.6 versus 34.9 percent and 124.8 versus 58.1 percent, respectively for the two strains) (p less than 0.01). Patients with opsonin activity of 50 percent or greater of standard had a greater response rate (73 versus 19 percent and 45 versus 0 percent for the two E. coli strains) (p less than 0.005 and p = 0.08, respectively). Eight of 10 patients with 75 percent or greater of standard for opsonic activity against their own blood stream isolates also responded, whereas zero of four with opsonins less than 75 percent of standard had a favorable outcome. These results indicate that serum opsonic activity may be a determinant of clinical response to granulocyte transfusion in infected granulocytopenic patients and may be predictive of outcome. We conclude that opsonic activity should be assessed in such patients before granulocyte administration and suggest a trial of plasma infusion in opsonin-deficient patients
— id: 24657, year: 1982, vol: 73, page: 552, stat: Journal Article,

Observer error in biopsy interpretations and outcome in chronic hepatitis
Kirschner E; Chalmers TC; Popper H; Gerber MA; Stenger RJ; Goldberg JD; Sacks H
1982 Nov-Dec;49(6):472-474, Mount Sinai journal of medicine
— id: 24656, year: 1982, vol: 49, page: 472, stat: Journal Article,

Essential thrombocythemia - response during first year of therapy with melphalan and radioactive phosphorus: a Polycythemia Vera Study Group
Murphy S; Rosenthal DS; Weinfeld A; Briere J; Faguet GB; Knospe WH; Landaw SA; Laszlo J; Pisciotta AV; Tartaglia AP; Goldberg JD; Berk PD; Donovan PB; Wasserman LR
1982 ;66:1495-1499, Cancer treatment reports
— id: 24757, year: 1982, vol: 66, page: 1495, stat: Journal Article,

Fetal outcome in narcotic-dependent women: the importance of the type of maternal narcotic used
Stimmel B; Goldberg J; Reisman A; Murphy RJ; Teets K
1982 83;9(4):383-395, American journal of drug & alcohol abuse
The records of 239 infants born to 228 women dependent on narcotic drugs were reviewed to determine if type of drug abused and adequacy of prenatal care would affect pregnancy and fetal outcome. Seventy-nine (33%) pregnancies occurred in women in supervised methadone maintenance, 78 (32%) in women on unsupervised methadone maintenance, 49 (21%) in women on street heroin, and 33 (14%) in women who were multiple drug users. Although the presence of withdrawal symptoms did not differ with respect to type of drug abused, the outcome was significantly better in those infants born to women on supervised methadone maintenance as compared to all other groups (p less than 0.001). There was no demonstrable relationship between the number of prenatal visits to the clinic and fetal outcome. A relationship could not be demonstrated between the maintenance dose during pregnancy and the presence of withdrawal symptoms in the infants born to women on supervised methadone maintenance. The findings of the study suggest that supervised methadone maintenance is compatible with an uneventful pregnancy and delivery. Neonatal complications, with the exception of withdrawal, do not appear to differ from that seen among infants born to nondrug dependent women
— id: 24683, year: 1982, vol: 9, page: 383, stat: Journal Article,

The use of cimetidine for the treatment of pruritus in polycythemia vera
Weick JK; Donovan PB; Najean Y; Dresch C; Pisciotta AV; Cooperberg AA; Goldberg JD
1982 Feb;142(2):241-242, Archives of internal medicine
Thirty-four patients with polycythemia vera complicated by pruritus were treated with 900 mg of cimetidine daily for 30 days and their responses to treatment were evaluated. The conditions of 15 (44%) were improved, with 12 patients stating that pruritus completely disappeared. Nineteen patients either showed no improvement or had increasing symptoms. No toxic effects were reported. The positive responses seen are encouraging and suggest that controlled studies are indicated to further evaluate the effectiveness of H2 antagonists
— id: 24659, year: 1982, vol: 142, page: 241, stat: Journal Article,

Mortality after first myocardial infarction. Search for a secular trend
Weinblatt E; Goldberg JD; Ruberman W; Frank CW; Monk MA; Chaudhary BS
1982 Mar 19;247(11):1576-1581, JAMA
Two earlier studies of prognosis of coronary heart disease among men enrolled in the Health Insurance Plan in the 1960s and 1970s permitted us to examine whether prognosis had improved over this ten-year period. The new comparison involved 1,133 men aged 35 to 64 years who had survived a first acute myocardial infarction and were followed up for mortality after a baseline examination. Mortality estimates were controlled for clinical and demographic differences between the two cohorts by multivariate methods and by comparing subgroups. The analyses showed no difference in long-term prognosis between patients in the two decades. The observations in this population suggest that any contribution of improved medical care to the nationally observed secular decline in mortality from coronary heart disease in the time period studied was probably restricted to the acute stage of myocardial infarction
— id: 24658, year: 1982, vol: 247, page: 1576, stat: Journal Article,

Granulomas do not affect postoperative recurrence rates in Crohn's disease
Wolfson, D M; Sachar, D B; Cohen, A; Goldberg, J; Styczynski, R; Greenstein, A J; Gelernt, I M; Janowitz, H D
1982 Aug;83(2):405-409, Gastroenterology
Previous studies have reached disparate conclusions on the issue of whether or not granulomas confer any protection against recurrence of Crohn's disease after operation. In an attempt to resolve this controversy, we have examined postoperative recurrence rates in 102 patients with Crohn's disease. There were no differences in cumulative postoperative recurrence-free survival between the 53 patients with granulomas present in the resected specimens and the 49 patients without granulomas. It was concluded that the presence of granulomas in resected specimens of Crohn's disease exerts no independent influence on the rate of postoperative recurrence
— id: 133219, year: 1982, vol: 83, page: 405, stat: Journal Article,

Filtration versus gravity leukapheresis in febrile granulocytopenic patients: a randomized prospective trial
Ambinder EP; Button GR; Cheung T; Goldberg JD; Holland JF
1981 May;57(5):836-841, Blood
Forty-eight patients with fever greater than 38.3 degrees C for at least 24 hr despite broad spectrum antibiotics and an absolute granulocyte count less than 1000/microliter were randomly allocated to 4 days of granulocyte transfusions obtained by leukapheresis using filtration (n = 27) or gravity (n = 21) techniques, the latter permitting simultaneous nonmechanical collection of granulocytes and platelets utilizing hydroxyethyl starch as a sedimenting agent. Patient characteristics and dose of granulocytes obtained from both techniques were similar. Complete response to granulocyte transfusions was established by a reduction in temperature to less than 37.2 degrees C sustained for at least 48 hr after the fourth transfusion with sterilization of cultures where previously positive and diminution of measurable infection when present. This occurred in 6/21 (29%) for gravity leukapheresis and 9/27 (33%) for filtration leukapheresis. An additional group had diminution in temperature and clinical improvement during transfusions (6/21 gravity leukapheresis versus 10/27 filtration leukapheresis). Eighty-six percent of patients transfused with gravity leukapheresis cells were alive at day 20 compared with 81% for filtration leukapheresis cells. Transfusion reactions were comparable. Thus, gravity leukapheresis appears to be as efficacious as filtration leukapheresis for treating granulocytopenic febrile patients, with the added advantages of availability to any blood bank without new equipment, of having platelets as by-products, and of not requiring donor heparinization
— id: 24662, year: 1981, vol: 57, page: 836, stat: Journal Article,

Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy
Berk PD; Goldberg JD; Silverstein MN; Weinfeld A; Donovan PB; Ellis JT; Landaw SA; Laszlo J; Najean Y; Pisciotta AV; Wasserman LR
1981 Feb 19;304(8):441-447, New England journal of medicine
In studies to determine the optimal treatment for polycythemia vera, 431 previously untreated patients whose disease met established diagnostic criteria were entered into a prospective, randomized controlled trial between 1967 and 1974. Three treatment regimens were used: phlebotomy alone, chlorambucil supplemented by phlebotomy, or radioactive phosphorus supplemented by phlebotomy. Despite minor differences in age and sex, the three groups were comparable in initial hematocrit, white-cell and platelet counts, and disease-related symptoms. The median duration of follow-up is now more than 6 1/2 years. As of February 15, 1980, there were no statistically significant differences in survival among the groups. However, the risk of acute leukemia in patients given chlorambucil was 2.3 times that in patients given radioactive phosphorus and 13 times that in patients treated with phlebotomy alone. The increased incidence of leukemia during chlorambucil treatment is statistically significant (P less than or equal to 0.002); accordingly, the Polycythemia Vera Study Group has discontinued the use of chlorambucil in the treatment of polycythemia vera
— id: 24664, year: 1981, vol: 304, page: 441, stat: Journal Article,

Improved chemotherapy for ovarian cancer with cis-diamminedichloroplatinum and adriamycin
Bruckner HW; Cohen CJ; Goldberg JD; Kabakow B; Wallach RC; Deppe G; Greenspan EM; Gusberg SB; Holland JF
1981 May 1;47(9):2288-2294, Cancer
In a prospective controlled randomized trial, patients with advanced ovarian carcinoma (FIGO Stage III or IV) were treated with cis-diamminedichloroplatinum (II), (DDP), alone, DDP and Adriamycin (ADM), or Triethylenethiophosphoramide (ThioTEPA) and methotrexate (MTX). DDP alone produces objective responses in 31% of evaluable patients, ThioTEPA and MTX in 36%. The combination of DDP and ADM produces the best response rate, 80% (.01 less than P less than 0.25). The risk of progression or death is substantially reduced for the two DDP regimens combined when compared with ThioTEPA-MTX (P = .03). Multivariate analysis further suggests the superiority of the two DDP regimens because poorly differentiated tumors and large, greater than 2 cm, residual tumors failed to produce their usual adverse effect on prognosis when patients were treated with the two DDP regimens. Patients with poorly differentiated tumors or tumors of unknown grade treated with platinum or DDP-ADM experienced better survival than similar patients treated with ThioTEPA (P = .01)
— id: 24663, year: 1981, vol: 47, page: 2288, stat: Journal Article,

Resistance to therapy of acute leukemia developing in the course of polycythemia vera
Donovan PB; Landaw SA; Dresch C; Gartenhaus WS; Goldberg JD; Ellis JT; Loeb V Jr; Perry MC; Petitt RM; Pisciotta AV; Silver RT; Spurr CL; Weinfeld A; Berk PD
1981 ;23(4):187-192, Nouvelle revue francaise d'hematologie
Thirteen patients in whom acute leukemia developed in the course of polycythemia vera were initially treated with vincristine and prednisone in an attempt at remission induction. None responded, and four died during this initial course of therapy. Induction was then attempted in the nine survivors, using cytosine arabinoside and adriamycin. Only one complete remission of 38 weeks and one partial remission were achieved, while median survival was 32 days. Poor results may reflect both the intrinsic biologic properties of the acute leukemia occurring in this setting and the advanced age of the patients
— id: 24665, year: 1981, vol: 23, page: 187, stat: Journal Article,

The evaluation of medical screening procedures
Goldberg JD; Wittes JT
1981 ;35:4-12, American statistician
— id: 24755, year: 1981, vol: 35, page: 4, stat: Journal Article,

Plasmapheresis in refractory generalized myasthenia gravis
Kornfeld P; Ambinder EP; Mittag T; Bender AN; Papatestas AE; Goldberg J; Genkins G
1981 Aug;38(8):478-481, Archives of neurology
A group of 16 patients with severe generalized myasthenia gravis (MG) (five with thymoma) that was resistant to anticholinesterases, thymectomy, and corticosteroids were treated by plasmapheresis. Twelve patients showed an excellent clinical response. Plasmapheresis is an effective treatment modality for many patients with severe generalized MG resistant to other forms of therapy. Unfortunately, the beneficial results are only transient and periodic plasmapheresis treatments are necessary
— id: 24672, year: 1981, vol: 38, page: 478, stat: Journal Article,

A comparison of androgens for anemia in patients on hemodialysis
Neff MS; Goldberg J; Slifkin RF; Eiser AR; Calamia V; Kaplan M; Baez A; Gupta S; Mattoo N
1981 Apr 9;304(15):871-875, New England journal of medicine
To compare the erythropoietic effects of nandrolone decanoate, testosterone enanthate, oxymetholone, and fluoxymesterone, we performed a randomized clinical trial in patients with anemia who were receiving maintenance hemodialysis (the women were not given testosterone enanthate). After a control period of at least two months, patients received one of the drugs for six months and then returned to control status; a second and third drug were administered in a similar fashion. Seventy-seven patients completed the first drug period, 56 the second, and 35 the third. The response to nandrolone and testosterone enanthate, the two drugs given by injection, was clearly superior to the response to oxymetholone or fluoxymesterone, given by mouth, in terms of the percentage of patients responding and the mean rise in hematocrit. Approximately half the patients had an increase of at least 5 percentage points in hematocrit after an injectable androgen was given; more than half the women responded. Patients who required transfusions regularly and those who had bilateral nephrectomies did not respond
— id: 24673, year: 1981, vol: 304, page: 871, stat: Journal Article,

Repeated 1 hour electrocardiographic monitoring of survivors of myocardial infarction at 6 month intervals: arrhythmia detection and relation to prognosis
Ruberman W; Weinblatt E; Frank CW; Goldberg JD; Shapiro S
1981 Jun;47(6):1197-1204, American journal of cardiology
In a study of the relation between ventricular premature beats and sudden death among 1,739 male of myocardial infarction enrolled in the Health Insurance Plan of Greater New York (HIP), patients underwent 1 hour of electrocardiographic monitoring at a baseline examination. During follow-up periods of up to 5 1/2 years, survivors underwent repeated monitoring at 6 month intervals for a maximum of four monitorings. At each monitoring a constant proportion of the men--25 percent--showed complex ventricular premature beats (runs of two or more, R on T phenomenon, bigeminal or multiform beats) during the hour. In comparison with men free of such arrhythmia, those demonstrating these complex forms in a given hour were three times as likely to show such beats in a subsequent monitoring hour. The mortality risk over 3 1/2 years after each of the four monitoring observations was in all cases elevated among men with complex ventricular premature beats. The risk of sudden death over this period was 6 percent for men without and 13 to 17 percent for men with such complexes. A study of the 1,445 men who underwent monitoring both at baseline examination and 6 months later identified the presence of runs of ventricular premature betas in either observation as a particularly important harbinger of sudden death
— id: 24661, year: 1981, vol: 47, page: 1197, stat: Journal Article,

Ventricular premature complexes and sudden death after myocardial infarction
Ruberman W; Weinblatt E; Goldberg JD; Frank CW; Chaudhary BS; Shapiro S
1981 Aug;64(2):297-305, Circulation
Among 1739 male survivors of myocardial infarction, mortality over 5 years was examined in relation to presence of complex ventricular premature complexes (R on T, runs of two or more, multiform or bigeminal complexes) identified during 1 hour of monitoring. Such arrhythmia was associated with excess risk of death over the entire period. Men with R on T or runs during the hour show a 5-year sudden coronary death rate of 25%, compared with 6% of men free of premature complexes. Men with complex ventricular premature complexes are also at relatively higher risk for nonsudden cardiac death than the other men (5-year mortality 15% and 7%, respectively), but no additional disadvantage was associated with the presence of R on T or runs. Multivariate survival analyses, controlling simultaneously for other important clinical factors, identify complex ventricular premature complexes as the strongest influence on risk of sudden coronary death and congestive heart failure as the strongest influence on risk of other cardiac death
— id: 24660, year: 1981, vol: 64, page: 297, stat: Journal Article,

Influence of therapy on causes of death in Polycythemia Vera
Wasserman LR; Balcerzak SP; Berk P; Berlin N; Donovan P; Dresch C; Ellis JT; Goldberg JD; Landaw SA; Laszlo J; McIntyre OR; Najean Y; Pisciotta AV; Silverstein MN; Tartaglia AP; Tatarsky I; Weinfeld A
1981 ;94:30-38, Transactions of the Association of American Physicians
— id: 24756, year: 1981, vol: 94, page: 30, stat: Journal Article,

Association of moncytic leukemia in patients with extreme leukocytosis
Cuttner J; Conjalka MS; Reilly M; Goldberg JD; Reisman A; Meyer RJ; Holland JF
1980 ;69:555-558, Blood
— id: 24754, year: 1980, vol: 69, page: 555, stat: Journal Article,

Cisplatin therapy of ovarian cancer
Holland JF; Bruckner HW; Cohen CJ; Wallach RC; Gusberg SB; Greenspan EM; Goldberg JD
Cisplatin, current status and new developments New York : Academic Press, 1980,
— id: 2649, year: 1980, vol: , page: 383, stat: Chapter,

Central nervous system involvement at presentation in acute granulocytic leukemia. A prospective cytocentrifuge study
Meyer RJ; Ferreira PP; Cuttner J; Greenberg ML; Goldberg J; Holland JF
1980 May;68(5):691-694, American journal of medicine
We have undertaken a perspective study of the prevelance of the central nervous disease in acute granulocytic leukemia (AGL). Thirty-nine newly diagnosed patients with AGL underwent cytocentrifuge examination of cerebral spinal fluid. Seven of the 39 patients had blast cells in their cerebral spinal fluid. All seven of these patients had acute myelomonocytic leukemia (AMML). No patients with other variants of AGL demonstrated blast cells in their cerebral spinal fluid. Other high risk factors associated with meningeal infiltration were elevated serum lysozyme levels, high peripheral white blood cell count, low age, splemomegaly and the presence of infiltration in other organs. The admission rates for patients with meningeal leukemia were lower and the survival time was shorter than in both the 32 noninvolved patients and the noninvolved patients with AMML. We believe that a lumbar puncture is indicated in all patients with newly diagnosed AMML
— id: 24675, year: 1980, vol: 68, page: 691, stat: Journal Article,

Ventricular premature complexes in prognosis of angina
Ruberman W; Weinblatt E; Goldberg JD; Frank CW; Shapiro S; Chaudhary BS
1980 Jun;61(6):1172-1182, Circulation
We studied the prognostic role of ventricular premature complexes occurring during 1 hour of electrocardiographic monitoring of 416 men with effort angina who had never had myocardial infarction, and compared mortality over 5 years with that of 1739 men with infarction before first observation. Multivariate analyses of survival identified the presence of ventricular premature complexes in 1 hour of monitoring, the presence of ST-segment depression on the standard ECG, and age as the variables making the most important independent contributions to risk of death (all causes and sudden coronary deaths) among the men with angina. The relatively lower age-adjusted 5-year mortality among men with angina compared with those who had a prior myocardial infarction reflects the lower prevalence in the former group of indicators of myocardial dysfunction, such as ventricular ectopic activity and ST-segment depression
— id: 24674, year: 1980, vol: 61, page: 1172, stat: Journal Article,

Origin and length of left main coronary artery: its relation to height, weight, sex, age, pattern of coronary distribution, and presence or absence of coronary artery disease
Abedin Z; Goldberg J
1978 ;4(3):335-340, Catheterization & cardiovascular diagnosis
The distance from the base of the left coronary sinus to the origin of the left main coronary artery was measured in 54 patients. The length of the left main coronary artery and the pattern of arterial dominance were determined in the last 37 patients. These variables were correlated with height, weight, age, sex, and presence or absence of coronary artery disease. Average distance from the basis of the left coronary sinus to the origin of the left main coronary artery was 19.4 +/- 2.7 mm. Average length of the left main coronary artery was 9.7 +/- 4.3 mm. There was a large inherent variability between distance from the base of left coronary sinus to the origin of the left main coronary artery and height of the subjects. Other variables did not show positive correlation. Similar large variability was noticed between of the left main coronary artery and height of the subjects. Thus, from these observations it was not possible to predict the distance from the base of the left coronary sinus to the origin of the left main coronary artery or the length of the left main coronary artery using height or any other variable. The importance of these findings in relation to coronary angiography is discussed
— id: 24676, year: 1978, vol: 4, page: 335, stat: Journal Article,

The estimation of false negatives in medical screening
Goldberg JD; Wittes JT
1978 Mar;34(1):77-86, Biometrics
In a medical screening program for early detection of disease, one or more screening modes are administered to an apparently healthy population. Knowledge of the true disease status for all screened individuals would allow estimation of the false negative and false positive rates for each mode of detection and for the program as a whole. This paper develops capture-recapture methods applicable to programs as a whole. This paper develops capture-recapture methods applicable to programs when follow-up of individuals negative on screening is not performed or is incomplete. The methods require at least two independent modes of detection. Data from a breast cancer screening program illustrate the procedure. The results of four screening examinations at approximately one-year intervals and the long-term follow-up of all screened individuals support the usefulness of these methods in the evaluation of a screening program
— id: 24667, year: 1978, vol: 34, page: 77, stat: Journal Article,

Biostatistical perspectives in the epidemiology of narcotic abuse
Smith H; Goldberg JD; Korts DC
1978 ;311:25-34, Annals of the New York Academy of Sciences
— id: 24775, year: 1978, vol: 311, page: 25, stat: Journal Article,

Detoxification from methadone maintenance: risk factors associated with relapse to narcotic use
Stimmel B; Goldberg JD; Cohen M; Rotkopf E
1978 ;311:178-180, Annals of the New York Academy of Sciences
— id: 24776, year: 1978, vol: 311, page: 178, stat: Journal Article,

Relation of education to sudden death after myocardial infarction
Weinblatt E; Ruberman W; Goldberg JD; Frank CW; Shapiro S; Chaudhary BS
1978 Jul 13;299(2):60-65, New England journal of medicine
We studied the influence of social and personal characteristics on prognosis among 1739 male survivors of myocardial infarction who had been monitored for one hour at a standard examination and subsequently followed for mortality. Over a three-year period men with little education (eight years of schooling or less) who had complex ventricular premature beats in the monitoring hour had over three times the risk of sudden coronary death found among better educated men with the same arrhythmia (cumulative mortality of 33 per cent and 9 per cent, respectively). No such differential appeared in the absence of complex ventricular premature beats. Neither risk factors for incidence of coronary heart disease nor clinical characteristics affecting prognosis accounted for the differences observed. There was no relation between education level and risk of recurrent infarction
— id: 24666, year: 1978, vol: 299, page: 60, stat: Journal Article,

Ventricular premature beats and mortality after myocardial infarction
Ruberman W; Weinblatt E; Goldberg JD; Frank CW; Shapiro S
1977 Oct 6;297(14):750-757, New England journal of medicine
To assess the role of ventricular premature beats in influencing mortality of coronary patients, 1739 men with prior myocardial infarction were monitored for ectopic activity for one hour at a standard base-line examination, and followed for mortality for periods up to four years (average, 24.4 months). Analyses of survival taking into account other important prognostic variables establish that the presence of complex premature beats (R on T, runs of 2 or more, multiform or bigeminal premature beats) in the monitoring hour is associated with a risk of sudden coronary death three times that of the men free of complex ventricular premature beats. The corresponding risk of death from any cause is twice that of men without such complex beats in the hour. These arrhythmias make an independent contribution to increased risk of death that persists over the length of this observation period
— id: 24668, year: 1977, vol: 297, page: 750, stat: Journal Article,

Malignancy in end-stage renal disease
Slifkin RF; Goldberg J; Neff MS; Baez A; Mattoo N; Gupta S
1977 ;23(3):34-40, Transactions (American Society for Artificial Internal Organs)
— id: 24677, year: 1977, vol: 23, page: 34, stat: Journal Article,

Ability to remain abstinent after methadone detoxification. A six-year study
Stimmel B; Goldberg J; Rotkopf E; Cohen M
1977 Mar 21;237(12):1216-1220, JAMA
Three hundred thirty-five persons successfully detoxified from methadone hydrochloride maintenance were followed up for as long as six years to determine their ability to remain abstinent from narcotic use. At the end of the observation period, of the 269 persons located, 35% were narcotic-free, 58% had returned to narcotic use, and 8% were either jailed or deceased. The ability of a person to refrain from narcotic use was found to be highly associated with staff's assessment of progress and duration of methadone maintenance treatment. Relapse to narcotic use occurred regardless of length of abstinence, with 35% of relapses occurring after three or more years. While abstinence after narcotic dependency is possible, it is not a realistic goal for all. Premature detoxification from methadone maintenance is associated with a high recidivism rate to narcotics
— id: 24678, year: 1977, vol: 237, page: 1216, stat: Journal Article,

The small cell lesion of mammary ducts and lobules
Toker C; Goldberg JD
1977 ;12 Pt 1(6 Suppl):217-249, Pathology annual
— id: 24688, year: 1977, vol: 12 Pt 1, page: 217, stat: Journal Article,

Prognostic value of one hour of ECG monitoring of men with coronary heart disease
Ruberman W; Weinblatt E; Frank CW; Goldberg JD; Shapiro S; Feldman CL
1976 Aug;29(8):497-512, Journal of chronic diseases
— id: 24669, year: 1976, vol: 29, page: 497, stat: Journal Article,

The effects of misclassification on the bias in the difference btetween two proportions and the relative odds in the fourfold table
Goldberg JD
1975 ;70:561-567, Journal of the American Statistical Association
— id: 24753, year: 1975, vol: 70, page: 561, stat: Journal Article,

Ventricular premature beats and mortality of men with coronary heart disease
Ruberman W; Weinblatt E; Frank CW; Goldberg JD; Shapiro S; Feldman CL
1975 Dec;52(6 Suppl):III199-III203, Circulation
Frequency and qualitative characteristics of ventricular premature beats (VPB) are determined from 1 hour of electrocardiogram (ECG) monitoring of men with coronary heart disease in a continuing study among members of the Health Insurance Plan of Greater New York. Mortality among 924 such men during an average observation period of 10 months was higher among men with VPB than among those free of VPB. In comparison with the routine 12-lead ECG, the hour of ECG monitoring increased the proportion of men identified as showing ectopic activity from 15% to 52%. Only half of men with 10 or more VPB in the hour of monitoring were noted as having VPB on the routine ECG; mortality among these men was relatively high whether or not VPB appeared on the short sample ECG
— id: 24687, year: 1975, vol: 52, page: III199, stat: Journal Article,

Lead time in breast cancer detection and implications for periodicity of screening
Shapiro S; Goldberg JD; Hutchison GB
1974 Nov;100(5):357-366, American journal of epidemiology
— id: 24670, year: 1974, vol: 100, page: 357, stat: Journal Article,

Appendix B: multivariate methos [to: Prognosis of women with newly diagnosed heart disease / Weinblatt E; Shapiro S; Frank CW]
Goldberg JD
1973 ;63:577-593, American journal of public health. AJPH
— id: 24752, year: 1973, vol: 63, page: 577, stat: Journal Article,

Risk factors in breast cancer - a prospective approach
Shapiro S; Goldberg JD; Venet L; Strax P
Host environment interactions in the etiology of cancer in man Lyon : International Agency for Research in Cancer, 1973,
— id: 2648, year: 1973, vol: , page: 169, stat: Chapter,