Showing papers by "Steven N. Goodman published in 2002"

Hypermethylation of the DNA repair gene O6-methylguanine DNA methyltransferase and survival of patients with diffuse large B-cell lymphoma

Abstract: Background: The gene encoding the DNA repair enzyme O 6 -methylguanine DNA methyltransferase (MGMT) is transcriptionally silenced by promoter hypermethylation in several human cancers, including diffuse large B-cell lymphoma (B-DLCL). MGMT promoter hypermethylation is a favorable prognostic marker in patients with brain tumors treated with alkylating agents. Methods: In a retrospective cohort study, we used methylation-specific polymerase chain reaction to analyze the MGMT promoter methylation status in tumor DNA of B-DLCL patients receiving cyclophosphamide as part of multidrug regimens. Molecular data were compared with patient response with the use of Student's t test. Disease-free survival and overall survival were estimated by the Kaplan-Meier method and compared with the use of the log-rank test. Multivariable survival analyses were performed with the Cox proportional hazards model. All statistical tests were two-sided. Results: Thirty (36%) of 84 B-DLCL patients showed MGMT promoter hypermethylation in their lymphomas. The presence of MGMT methylation was associated with a statistically significant increase in overall survival (hazard ratio for time to death for nonmethylation versus methylation = 2.8; 95% confidence interval (CI) = 1.2 to 7.5; P = .01) and progression-free survival (hazard ratio for time to progression for nonmethylation versus methylation = 2.6; 95% CI = 1.3 to 5.8; P = .02). MGMT promoter hypermethylation was both independent of and stronger than established prognostic factors, such as age, disease stage, serum lactic dehydrogenase level, and performance status. Conclusion: MGMT promoter hypermethylation appears to be a useful marker for predicting survival in patients with B-DLCL treated with multidrug regimens including cyclophosphamide.

Assessment of Plasma DNA Levels, Allelic Imbalance, and CA 125 as Diagnostic Tests for Cancer

Abstract: Background: Allelic imbalance (AI), the loss or gain of chromosomal regions, is found in many cancers. AI can be detected in genomic tumor DNA released into the blood after necrosis or apoptosis. We evaluated plasma DNA concentration, allelic status in plasma DNA, and serum CA 125 level as screening tests for ovarian and other cancers. Methods: Plasma samples were obtained from 330 women (44 normal healthy control individuals, 122 patients with various cancers, and 164 control patients with non-neoplastic diseases). Plasma DNA concentration was determined in all samples. Allelic status was determined by digital single nucleotide polymorphism (SNP) analysis with eight SNP markers in plasma DNA from 54 patients with ovarian cancer and 31 control patients. CA 125 was determined in 63 samples. Receiver-operating characteristic (ROC) curves were plotted, and the areas under the ROC curves—a measure of the overall ability of a diagnostic test with multiple cutoffs to distinguish between diseased and nondiseased individuals— were determined. Results: The area under the ROC curve for plasma DNA concentration was 0.90 for patients with neoplastic disease versus healthy control individuals and 0.74 for patients with neoplastic diseases versus control patients with non-neoplastic diseases. For control subjects given a specificity of 100% (95% confidence interval [CI] = 92% to 100%), the highest sensitivity achieved was 57% (95% CI = 49% to 67%). AI in at least one SNP was found in 87% (95% CI = 60% to 98%) of patients with stage I/II ovarian cancer and 95% (95% CI = 83% to 99%) of patients with stage III/IV ovarian cancer, but AI was not found in 31 patients with non-neoplastic diseases (specificity = 100%, 95% CI = 89% to 100%). The area under the ROC curve assessing AI was 0.95. Combining the serum CA 125 level with the plasma DNA concentration increased the area under the ROC curve from 0.78 (CA 125 alone) to 0.84. Conclusion: Plasma DNA concentration may not be sensitive or specific enough for cancer screening or diagnosis, even when combined with CA 125. AI was detected with high specificity in plasma DNA from patients with ovarian cancer and should be studied further as a screening tool. [J Natl Cancer Inst 2002;94:1697–1703]

Acne therapy: a methodologic review.

Abstract: Background: Acne is a very common problem with significant physical and psychological morbidity. The evidence basis for its treatment had not been systematically reviewed. Therefore, we performed an evidence review to provide researchers a basis for further studies, and to provide clinicians the background needed to interpret current and future clinical studies. Objective: We summarize the methodologic state of the acne literature in patients with acne who do not have complicating co-morbidities. Methods: This was an expert-advised literature synthesis. We used a structured literature search for English-language controlled trials in Cochrane CENTRAL, MEDLINE, OLDMEDLINE, HSTAT, CINAHL, and PsychInfo. Results underwent a structured data abstraction process, with review by at least 2 reviewers. Results: Out of 1588 unique articles, 250 articles (274 controlled trials) over the past 50 years were reviewed: 57 (21%) trials had at least one major weakness and no strengths; 125 (47%) trials had at least one major strength and at least one major weakness; 48 (18%) trials had at least one major strength, and no major weaknesses. The remaining 16 (6%) were of intermediate quality or did not provide enough information to make a determination. One fourth of studies did not report patient age; one fourth did not report on patient gender. Only 8% mentioned patient race; only 2% mentioned skin type; 0.4% mentioned diet; none scored sexual maturity or insurance status. There were 1237 outcomes. There were more than 25 methods of assessing acne severity and more than 19 methods for counting lesions. There were only two trials that formally assessed psychological outcomes. More than 140 treatments were tested in 251 comparisons. Conclusion: Ranging over 50 years of research, the acne literature evidences great heterogeneity at all levels: patient characteristics, acne severity, outcome assessments, treatments, and comparisons. A list of methodologic recommendations is provided. (J Am Acad Dermatol 2002;47:231-40.)

How Statistical Expertise Is Used in Medical Research

Abstract: ContextInvestigation of the nature and frequency of statistician involvement in medical research and its relation to the final editorial decisionMethodsAuthors of original research articles who submitted to BMJ and Annals of Internal Medicine from May through August 2001 were sent a short questionnaire at the time of manuscript submission Authors were asked if they received assistance from a person with statistical expertise, the nature of any such contribution, and reasons why, if no statistical input was receivedResultsThe response rate was 75% (704/943); methodological input was reported for 514 (73%) of these papers In 435 papers (85%), such input was provided by biostatisticians or epidemiologists and, if deemed significant, was typically associated with authorship A total of 33 of 122 methodologists (27%) whose main contribution started at the analysis stage received neither acknowledgment nor authorship Research without methodological assistance was more likely to be rejected without review (71% vs 57%; χ2 = 106; P = 001) and possibly less likely to be accepted for publication (7% vs 11%; χ2 = 237; P = 12)ConclusionsStatistical input to medical research is widely recommended but inconsistently obtained Individuals providing such expertise are often not involved until the analysis of data and many go unrecognized by either authorship or acknowledgment

The Mammography Dilemma: A Crisis for Evidence-Based Medicine?

Abstract: The newest contretemps over mammography is yet the latest eruption from a debate that has been simmering for decades. But a closer look at this controversy, which is officially joined here by publi...

Scorpions from the Daraina region of northeastern Madagascar, with special reference to the family Heteroscorpionidae Kraepelin, 1905

Abstract: El trabajo de campo llevado a cabo recientemente en la zona boscosa de Daraina, en al noreste de Madagascar, ha permitido la recogida de diez escorpiones pertenecientes a dos generos diferentes, Heteroscorpion Birula (Heteroscorpionidae) y Tityobuthus Pocock (Buthidae). En ambos hay espacies nuevas para la ciencia que seran con toda probabilidad endemicas de la region de Daraina, donde los fragmentos de bosque que quedan contienen habitats de transicion unicos. El aspecto mas notable de la espacie nueva de Hateroscorpion es su tamano, al oscilar los adultos entra 140 y 180 mm de longitud, que lo convierte en el mayor escorpion encontrado hasta ahora en Madagascar. Tambien se comentan los resultados del estudio de las estructuras pectinales, llevado a cabo con microscopio electronico.

Pancreatic cancer after remote peptic ulcer surgery

Abstract: Background: Peptic ulcer surgery may carry an increased risk for pancreatic cancer development. Molecular analysis of K-ras codon 12, frequently mutated in conventional pancreatic cancers, might provide insight into the aetiological mechanisms. Methods: The relative risk of pancreatic cancer was computed by multivariate and person–year analysis in a cohort of 2633 patients who had undergone gastrectomy. Lung cancer risk was analysed as an indirect means of assessing smoking behaviour. K-ras codon 12 mutational analysis was performed on 15 postgastrectomy pancreatic cancers. Results: There was an overall increased risk of pancreatic carcinoma of 1.8 (95% confidence interval, 1.3 to 2.6) five to 59 years postoperatively, which gradually increased to 3.6 at 35 years or more after surgery (κ 2 test for trend, p Conclusions: Remote partial gastrectomy is associated with an increased risk of pancreatic cancer. Postgastrectomy and non-postgastrectomy pancreatic cancers may share similar aetiological factors, such as smoking. However, the neoplastic process in patients who have undergone gastrectomy appears to be accelerated by factors related to the surgery itself.