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Biomedical subjects

D S Weinberg

Publications and source records attributed to D S Weinberg.

At least 19 recordsLinked to original sources
PubMed2001

Risk of colorectal cancer after breast cancer.

BACKGROUND: History of breast cancer has been reported as a risk factor for colorectal cancer in women. In view of the ambiguous nature of existing evidence and the growing interest in targeted colorectal cancer prevention, we sought to quantify this risk. METHODS: We used the Surveillance Epidemiology and End Results (SEER) database to estimate risk of colorectal cancer after breast-cancer diagnosis in women with first incident breast cancer between 1974 and 1995. Observed colon and rectal cancer risk was compared with that expected in the general population. We stratified comparisons by age at breast-cancer diagnosis, stage of cancer, ethnic origin of patient, and follow-up time. FINDINGS: Overall, women with previous breast cancer were 5% less likely (95% CI 1-9) to develop colon and 13% less likely (6-19) to develop rectal cancer than women in the general population. Stratified analyses suggested that the risk reductions observed for colon and rectal cancer were most pronounced for women with breast cancer diagnosed after age 65 years, in white women, women with local stage breast cancer, and women diagnosed in the later study years (1990-94). INTERPRETATIONS: Breast cancer does not increase subsequent colorectal cancer risk, and reduced risk was seen for certain subgroups of women. Because no biologically plausible endogenous protective factor has been identified, we suggest that reduced risk could stem from an accumulation of exposures that increase breast-cancer frequency but protect against colorectal cancer.

Adult↗
PubMed2000

Quantification of (+)-calanolide A, a novel and naturally occurring anti-HIV agent, by high-performance liquid chromatography in plasma from rat, dog and human.

A HPLC method was validated for quantification of (+)-calanolide A (1), a novel anti-HIV agent, in rat, dog and human plasma. The synthetic intermediate (+/-)-12-oxocalanolide A (2) was found to be a suitable internal standard. Compounds were extracted from plasma using a solid-phase C(18) cartridge and quantified over the assay range of 12.5 to 800 ng/ml. The method was utilized to determine (+)-calanolide A pharmacokinetics in rats, dogs and humans. This is the first report of a validated HPLC assay for determination of (+)-calanolide A concentrations in rat and dog plasma as well as human plasma obtained from clinical trials. There was no evidence of in vivo epimerization of (+)-calanolide A to its inactive epimer (+)-calanolide B (3).

Administration, Oral↗
PubMed2000

Human cholecystokinin-A receptor is not an oncofetal protein.

The CCK-A (cholecystokinin-A) receptor is selectively expressed by human pancreatic adenocarcinomas, suggesting a possible role in pancreatic tumorigenesis. In animals, pancreatic CCK receptor expression varies during ontogeny and neoplastic transformation. This study examined the temporal expression of CCK receptors in human fetal, postnatal, and adult pancreas to determine whether the appearance of CCK-A receptors in pancreatic adenocarcinomas reflected oncofetal antigen or pancreatic neoantigen expression. Messenger ribonucleic acid (mRNA) was isolated from six paraffin-embedded normal pancreatic autopsy specimens ranging in age from 17 weeks postfertilization through 26 days following full-term delivery, and samples of adult human tissues, including pancreas and pancreatic adenocarcinoma. Using reverse transcription-polymerase chain reactions, CCK-B receptor mRNA was expressed in all specimens of normal fetal and postnatal human pancreas, adult pancreas, and pancreatic adenocarcinomas. CCK-A receptor mRNA was selectively expressed only in pancreatic adenocarcinomas. These data suggest that selective CCK-A receptor expression in pancreatic adenocarcinomas reflects neoantigen expression in humans.

Adenocarcinoma↗
PubMed2000

Postoperative management of local colorectal cancer: therapy and surveillance.

Adjuvant therapy is widely recommended for stage III colon cancer and stages II and III rectal cancer. Although fluorouracil-based regimens are standard, newer agents either alone or in combination may improve response rates. Although nearly all patients enter a postoperative surveillance program after surgical resection, the clinical effectiveness of such surveillance, which is not standardized, is questionable. Critical review of the use of different components (laboratory, radiographic, and endoscopic) of these programs finds little support for intensive surveillance.

Colorectal Neoplasms↗
PubMed1999

Risk for colorectal cancer after gynecologic cancer.

BACKGROUND: Studies have suggested that women with previous diagnoses of gynecologic cancer (cervical, endometrial, or ovarian) have an increased risk for colorectal cancer. OBJECTIVE: To quantify risk for colorectal cancer after gynecologic cancer, both overall and for subgroups defined by age at diagnosis, cancer stage at diagnosis, ethnicity, and duration of follow-up. DESIGN: Retrospective cohort analysis of the Surveillance, Epidemiology, and End Results (SEER) program database from 1974 through 1995. SETTING: U.S. cancer registry. PATIENTS: 21,222 patients with cervical cancer, 51,680 patients with endometrial cancer, and 28,832 patients with ovarian cancer. MEASUREMENTS: Standardized incidence ratios (SIRs) were calculated for each gynecologic cancer site and for subgroups to represent the relative risk for colorectal cancer in women with previously diagnosed gynecologic cancer compared with women without gynecologic cancer. Poisson regression methods adjusting simultaneously for all study variables were used to estimate relative risks for colorectal cancer across subgroups with each gynecologic cancer. RESULTS: Overall, risk for colorectal cancer was elevated among women with previous ovarian cancer (SIR, 1.36 [95% CI, 1.21 to 1.53]). Risk was greatest in women who received a diagnosis before 50 years of age (SIR, 3.67 [CI, 2.74 to 4.80]) but was also elevated in women who received a diagnosis between 50 and 64 years of age (SIR, 1.52 [CI, 1.25 to 1.83]). The risk for colorectal cancer after endometrial cancer was also elevated substantially if endometrial cancer was diagnosed before the age of 50 (SIR, 3.39 [CI, 2.73 to 4.17]). No apparent risk elevation was associated with previous cervical cancer. CONCLUSIONS: Previous endometrial or ovarian cancer, particularly when diagnosed at an early age, increases subsequent risk for colorectal cancer. Greater emphasis on colorectal cancer screening in these populations may be necessary.

Adult↗
PubMed1999

How can physicians keep up-to-date?

Keeping one's personal fund of knowledge current is one of the most formidable challenges that physicians face. This article considers a few strategies that may help physicians as they struggle to keep their knowledge up-to-date. Physicians need to develop their own goals for staying current, systematically and periodically search the literature for high-quality material relevant to the topics on their agendas, become facile with critical appraisal of the literature, and schedule time for reading. One of the responsibilities of any professional is to maintain expertise, and this responsibility is probably nowhere more critical, or more difficult, than in the profession of medicine.

Clinical Competence↗
PubMed1998

Effect of histamine-2 receptor antagonists on blood alcohol levels: a meta-analysis.

OBJECTIVE: To determine the effect, if any, of histamine type 2 receptor antagonists (H2RAs) on serum alcohol levels under various conditions including type of H2RA receptor antagonist, alcohol dose, and fed status of the subject. STUDY DESIGN: Meta-analysis of the published literature. DATA SOURCES: Studies were identified by MEDLINE (January 1982 through December 1997) using the key words H2 receptor antagonists and alcohol. Other studies were identified by reviewing bibliographies of retrieved articles and by discussion with colleagues. STUDY SELECTION: Studies were selected if they involved the coadministration of H2RAs and alcohol in healthy, human volunteers. Studies that may have addressed this goal but were performed in another context, for instance the measurement of ulcer healing, were excluded. DATA EXTRACTION: Data were extracted on the design, number of participants, participant characteristics, type and dose of H2RA administered, serum alcohol levels (measured as Cmax) along with standard deviations, dose of alcohol received, and fed or fasted status of participants. Alcohol dose was arbitrarily divided into low dose (< or = 0.5 g/kg body weight) versus high dose (> 0.5 g/kg body weight). In addition, studies involving ranitidine and cimetidine were stratified by sample size into small (n < or = 10) versus not small (n > 10). MEASUREMENTS AND MAIN RESULTS: Twenty-four trials met selection criteria. Small elevations in Cmax were noted when cimetidine (2.71 mg/DL; 95% confidence internal [CI] 1.60, 3.83) or ranitidine (6.95 mg/DL; 95% CI 5.83, 8.08) were coadministered with alcohol. No such differences were noted for famotidine (0.28 mg/DL; 95% CI -1.24, 1.80) or nizatidine (2.33 mg/DL;, 95% CI -0.06, 4.72). The elevation detected with cimetidine and ranitidine was most pronounced in smaller studies (n < 10). Separate analyses investigating the effect of alcohol dose and fed or fasted status of participants revealed no clinically important differences. CONCLUSIONS: Cimetidine and ranitidine, but not the other H2RAs, can cause small elevations of serum alcohol level when alcohol and drug are administered concurrently. Studies with larger numbers of participants were less likely to demonstrate this effect. Relative to accepted, legal definitions of intoxication, the effect of any H2RA on blood alcohol level is unlikely to be clinically relevant.

Cimetidine↗
PubMed1997

Cholecystokinin A and B receptors are differentially expressed in normal pancreas and pancreatic adenocarcinoma.

Cholecystokinin (CCK) plays an important role in pancreatic carcinogenesis. While human CCK-A and -B receptors have been fully characterized, their relative roles in human pancreatic adenocarcinoma remain unclear. Thus, expression of CCK-A and -B receptors in normal human pancreas, pancreatic adenocarcinomas, and other human extrapancreatic tissues and malignancies was examined, using reverse transcription followed by the polymerase chain reaction (RT-PCR). mRNA isolated from 15 normal pancreas specimens, 22 pancreatic adenocarcinomas, and 58 extrapancreatic tissues and tumors was subjected to RT-PCR using primers specific for human CCK-A and -B receptors. Expression of CCK-B receptors was detected in all tissues arising from pancreas and in most extrapancreatic tissues and tumors. In contrast, CCK-A receptors exhibited a more selective pattern of expression in gall bladder, intestine, brain, ovary, spleen, and thymus. Of significance, CCK-A receptors were expressed selectively in all pancreatic adenocarcinomas, but not in any normal pancreas specimens. In situ hybridization, using receptor-specific riboprobes, localized CCK-A receptor expression to ductal cells, the presumed origin of most human pancreatic adenocarcinomas. Southern blot analysis revealed no evidence of CCK-A receptor gene amplification or rearrangement in pancreatic adenocarcinomas. Because of its selective expression, the CCK-A receptor may serve as selective biomarker for pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Color images in telepathology: how many colors do we need?

It is generally assumed that for telepathology, accurate depiction of microscopic images requires the use of "true color" (ie, 24 bits, eight bits each for red, green, and blue) in the digitized image used for transmission. If such a 24-bit color image file, which provides a palette of 16.7 million colors, could be reduced in size by decreasing the possible numbers of colors displayed in the image to 8 bits (palette of 256 colors), the image files would require less storage space, could be transmitted more rapidly, and would require less telecommunications bandwidth. However, such color reduction must not result in detectable image degradation, especially if the images are to be used for diagnosis. Therefore, we performed a carefully controlled study to determine whether pathologists could detect differences in the quality of microscopic images that were reduced from 24 to 8 bits of color. Thirty pathologists were each asked to view a set of 30 image pairs displayed on a computer monitor. Each image pair consisted of the original 24-bit color version and an 8-bit color-reduced version, derived using an adaptive color reduction algorithm with diffusion dithering. Observers were asked whether they could detect any difference in quality between the image pairs. Then, regardless of their answer, they were asked to choose the better quality image of the pair. Overall, there was not a statistically significant ability to consciously detect differences between the image pairs (P < .750). However, when forced to choose, there was a significant preference for the 8-bit images as being of "better quality" (P < .005). We conclude that telepathology applications may be able to take advantage of adaptive color reduction algorithms to reduce image file size without sacrificing image quality. Additional studies must be performed to determine the minimal image requirements for accurate diagnosis by telepatholgy.

Color↗
PubMed1997

T-cell blast crisis in chronic myelogenous leukemia. Immunophenotypic and molecular biologic findings.

T-cell blast crisis in chronic myelogenous leukemia is rare. We examined three patients (ages 35 to 72 years) in whom T-cell blast crisis developed 11 to 36 months (mean, 25 months) after diagnosis of chronic myelogenous leukemia and who died 4 to 12 months (mean, 7 months) thereafter. Two patients had diffuse lymphadenopathy, and the third had marked lymphocytosis (white blood cell count 217,000/microL, with 90% circulating blasts). In all three patients, neoplastic cells had the appearance of lymphoblasts and were immunoreactive for T-cell markers by immunohistochemical or flow cytometric analysis or both. Molecular diagnostic studies revealed the presence of a bcr-abl oncogene rearrangement in all three cases, but none exhibited a clonal T-cell receptor delta, beta, or gamma chain gene rearrangement. One case exhibited deletion of the J delta 1 region of both delta chain genes. The significance of these findings is discussed, and they are compared with those of other reported cases of T-cell blast crisis in chronic myelogenous leukemia.

Adult↗
PubMed1997

Digital imaging as a teaching tool for pathologists.

Digital Imaging is a technology which should be of considerable interest to pathologists as the use of gross and microscopic pathology images plays an important part in their role as medical educators. Digital imaging may have important advantages over conventional film photography which can be exploited by the pathologist to create all-digital presentations. In this article, the basic components of digital imaging are described, along with an affordable and practical approach which should allow most pathologists to begin to explore this medium.

Computers↗
PubMed1996

Aggressive variants of chromophobe renal cell carcinoma.

BACKGROUND: Chromophobe renal cell carcinoma (RCC) is a distinctive subtype of RCC with a more favorable prognosis than clear cell RCC. We describe the pathologic features of 23 solitary cases and 2 cases with coexistent papillary RCCs, 7 of which developed metastases. METHODS: Cases were retrieved from the pathology files of our institutions. Clinical follow-up was obtained from the medical records. DNA analysis was performed on Feulgen-stained slides using image analysis. RESULTS: Twenty-five cases were identified. All cases had characteristic pathologic features, including diffuse cytoplasmic reactivity for Hale's colloidal iron. DNA ploidy analysis of ten cases revealed a diploid pattern in five, a hyperdiploid pattern in four, and a hypodiploid pattern in one. Follow-up was available for 20 cases, and metastases developed in 7 (from 4 to 120 months after surgery). In 5 of these cases, the tumors were solitary and more than 8 cm in greatest dimension and metastases developed in the liver. In both cases with papillary RCCs in the same kidney, metastases developed in the lung, although which tumor metastasized is unknown. CONCLUSIONS: Despite the overall favorable prognosis for chromophobe RCC, large tumors and those with coexistent papillary RCCs may produce in metastases.

Adenocarcinoma↗
PubMed1996

Modulated expression of notch1 during thymocyte development.

The Notch gene family encodes transmembrane proteins that have been implicated in control of diverse cellular differentiation events in the fly, frog, and mouse. Mammalian Notch1 is expressed at high levels in thymus and is mutated in a subset of human T-cell acute lymphoblastic neoplasms, suggesting a role in T-cell differentiation. To investigate the patterns of expression of NOTCH1 protein in thymocytes of the developing and mature thymus, antibodies raised against NOTCH1 were used to perform immunohistochemical and flow cytometric analyses. Strong staining for NOTCH1 within the fetal murine thymus was observed as early as 13.5 days postcoitum. By 17.5 days postcoitum, preferential staining of superficial cortical thymocytes was observed, with weak staining of developing medulla. Flow cytometric analysis and immunohistochemical staining of flow-sorted cells confirmed that the highest levels of NOTCH1 expression in adult murine thymus were present in immature cortical thymocytes (CD24high, CD4-CD8-). In contrast, NOTCH1 expression was low or absent in more mature cortical thymocytes (CD24low, CD4+CD8+), whereas intermediate levels of expression were observed in CD4+CD8- and CD4-CD8+ cells. These data indicate a dynamic pattern of NOTCH1 expression during T-cell differentiation and suggest that downregulation of NOTCH1 may be required for maturation of cortical thymocytes.

Animals↗
PubMed1996

The diagnosis and management of gastroesophageal reflux disease.

GERD is a common clinical problem. Generally, its clinical presentation and management are straightforward. Greater awareness of the numerous extraesophageal manifestations of the disease aids patients and physicians in appropriate recognition and treatment. Medical therapy is effective in the majority of cases but often requires long-term medication for acceptable symptom control. A small, but significant proportion of patients presents with or develops complications of GERD, most importantly Barrett's esophagus. Although the logistics of long-term surveillance of persons with Barrett's esophagus is unclear, the association of this metaplastic change with esophageal adenocarcinoma underscores the importance of regular follow-up.

Barrett Esophagus↗
PubMed1996

Telepathology diagnosis by means of digital still images: an international validation study.

Telepathology affords the means to provide pathological diagnosis and consultation to remote sites. However, before telepathology can become an acceptable medical tool, it will be vital to determine the diagnostic accuracy of this technology. We report the results of a single-blind study of the accuracy of diagnosis performed using computerized still images obtained from a telepathology workstation used in a French telepathology network. Four pathologists, each working alone, reviewed a total of 200 cases of routine surgical pathology (50 cases each), and performed diagnosis based on both computer CD-ROM still images (CD) and conventional glass slides (GS). Concordance between GS and CD diagnosis, as well as accuracy, were determined. Other factors related to performance were also measured, including diagnostic certainty, reasons for uncertainty, and causes of diagnostic error. Overall, there was good agreement between CS and CD diagnosis. There was 87.5% concordance between CS and CD diagnosis, and comparison to consensus (correct) diagnosis showed accuracy of 95.5% and 88.5% for GS and CD diagnosis, respectively. Marked variability in accuracy of CD diagnosis was observed among the four pathologists, and issues related to image selection and/or quality appeared responsible for 60% of the diagnostic errors. The lack of sufficient images and clinical information were frequently cited as reasons for diagnostic uncertainty, as well as feelings of insufficient expertise. It is likely that the opportunity for interaction with the referring pathologist and the use of subspecialty consultants would likely improve the performance of telepathology.

CD-ROM↗