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Biomedical subjects

M B Cohen

Publications and source records attributed to M B Cohen.

At least 145 records · Page 8Linked to original sources
PubMed1994

Genomic sequence of the murine guanylin gene.

Guanylin, a 15-amino-acid peptide, is an endogenous ligand of the intestinal receptor guanylate cyclase-C. After binding to this receptor, guanylin increases the intracellular concentration of cyclic GMP and induces chloride secretion. We have isolated a genomic clone containing the entire murine guanylin gene. The guanylin gene is composed of three exons that span 1700 bp. The first 133 nucleotides of upstream promoter sequence lack the canonical TATA, CAAT, and SP1 elements. Guanylin transcription is nearly exclusively limited to the intestine, and the presence of guanylin mRNA is greatest in the distal colon and ileum. Therefore, characterization of the guanylin promoter is likely to provide another paradigm for intestine-specific gene regulation.

Amino Acid Sequence↗
PubMed1994

DNA ploidy and P-glycoprotein expression as predictive factors of response to neoadjuvant chemotherapy for invasive bladder cancer.

OBJECTIVE: To identify a factor or factors that could predict response of muscle invasive transitional cell carcinoma of the bladder to neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy. METHODS: DNA ploidy analysis and immunohistochemical staining for p-glycoprotein (the product of the multidrug resistance gene, MDR-1) were performed on bladder biopsies obtained prior to chemotherapy. Radical cystectomy specimens were utilized for complete pathologic staging. RESULTS: Tissue was available for DNA ploidy analysis in 25 patients. Ten patients had complete responses to neoadjuvant chemotherapy and 15 patients did not respond. Nineteen patients had aneuploid tumors, of which 7 (37%) were complete responders. Six patients had diploid tumors, of which 3 (50%) were complete responders. This difference was not statistically significant. Tissue was available for immunostaining in 15 patients. Seven of 9 patients (78%) who did not respond to chemotherapy stained positively for p-glycoprotein, whereas 5 of 6 patients (83%) who had complete responses stained positively. This difference was not statistically significant. CONCLUSIONS: Neither DNA ploidy nor p-glycoprotein expression appears to predict successfully those patients likely to respond to neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy in the treatment of invasive bladder cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Absence of immunohistochemical metallothionein staining in bladder tumor specimens predicts response to neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy.

Pre-chemotherapy bladder tumor tissue was retrospectively analyzed in 21 patients treated with neoadjuvant cisplatin, methrotrexate and vinblastine. Immunohistochemical staining for 2 proposed mediators of drug resistance, p-glycoprotein and metallothionein, was performed and compared to chemotherapeutic response and survival. There was no significant relationship between staining for p-glycoprotein and the response to chemotherapy or survival. Patients with no detectable staining for metallothionein were statistically more likely to sustain a complete pathological response (p = 0.029) after chemotherapy than those with any detectable staining. No relationship between metallothionein immunostaining and survival was apparent. This study offers further evidence linking metallothionein in tumor resistance to cisplatin containing chemotherapy regimens.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Primary osteogenic sarcoma of the urinary bladder successfully treated with combination therapy.

A 54-year-old woman presented with a large bladder mass and left hydroureteronephrosis. At radical cystectomy (with ileal loop urinary diversion), an unresectable left obturator mass was found. Combination chemotherapy postoperatively resulted in significant shrinkage, and she underwent excision of the residual mass. No residual cancer was seen. The patient remains free of disease 56 months after cystectomy and 51 months after resection of the residual mass. Primary osteogenic sarcoma of the urinary bladder may respond to combination chemotherapy and surgery. All patients found to have advanced disease should be considered for this approach.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Laparoscopic approaches to the treatment of intrinsic urethral weakness (type III stress urinary incontinence).

The treatment of intrinsic urethral weakness (Type III stress urinary incontinence) has traditionally been accomplished by the performance of a sling cystourethropexy or the placement of an artificial urinary sphincter. As experience with operative laparoscopy continues to increase, the possibility of performing these procedures from a laparoscopic approach becomes realistic. We report our experience with the laparoscopic performance of a sling cystourethropexy and placement of an artificial urinary sphincter in the canine model. On the basis of initial results, we believe these techniques are feasible in human subjects.

Animals↗
PubMed1994

Review of negative Papanicolaou tests. Is the retrospective 5-year review necessary?

New federal regulations require review of all available negative gynecologic smears within the previous 5 years for each patient with a current high grade squamous intraepithelial lesion (HGSIL) or above. Two university hospitals retrospectively reviewed all patients who had HGSIL or above and who had prior negative smears. During 18 months, 35,807 Papanicolaou tests were reported, from which we identified 44 patients with 80 negative smears before presenting with HGSIL or above. These 80 negative smears were rescreened and, on review, there was agreement with the original diagnosis in 66 cases (82.5%). Fourteen (17.5%) smears were reclassified: 2 unsatisfactory, 6 atypical squamous/glandular cells of undetermined significance, 3 low grade SIL, and 3 HGSIL or above. Of the 12 cases satisfactory for reclassification, 9 (75%) occurred within 2 years before the HGSIL or above. Two cases of atypical squamous/glandular cells occurred within 4 years. One case of HGSIL occurred more than 4 years before, but a negative Pap smear had been reclassified within the year before the diagnosis of HGSIL. The authors conclude that a 2-year retrospective review, which identified 75% of our false-negative cases, is an effective and efficient quality control and assurance practice.

False Negative Reactions↗
PubMed1994

Sampling of radical prostatectomy specimens. How much is adequate?

Prostate glands from 52 patients with clinical stage B carcinoma were examined using two sampling techniques. After fixation and conization of the apical portions, each gland was serially sectioned with sections mounted whole on oversized glass slides and examined for pathologic features of prognostic importance. A second examination was subsequently conducted on the same tissue using only alternate sections. No differences in tumor type, grade, Gleason score, multiplicity, or capsular penetration were detected in 75% of cases. The discrepancies that did occur were most often minor variations in multiplicity and Gleason score. Of the 20 glands with capsular penetration observed with the serial sectioning method, 17 (85%) were detected using alternate sectioning. The surgical margin was involved in two of the three invasive foci that would have been missed. Although the topography is better displayed, the authors' examinations indicated no significant advantage to whole mount sections compared with sections mounted on standard-sized glass slides. Considering the most effective use of resources, as well as the current modalities available for patient monitoring, the results support the use of an alternate sectioning method for pathologic examination of specimens removed for clinically localized prostate cancer.

Carcinoma↗
PubMed1994

Upregulation of Escherichia coli heat-stable enterotoxin receptor in regenerating rat liver.

Guanylate cyclase C (GC-C) is a transmembrane protein that serves as a receptor for the recently characterized endogenous ligand guanylin and for Escherichia coli heat-stable toxin (STa). Binding of either guanylin or STa to intestinal GC-C results in net chloride secretion. Although GC-C is expressed in the rat intestine throughout life, its expression in the rat liver has previously been shown to occur only during the perinatal period. As a step toward elucidating the role of this receptor in the liver, we tested the hypothesis that GC-C mRNA expression could be induced in the adult rat liver following 1) partial hepatectomy, a stimulus for hepatocyte proliferation; 2) intraperitoneal carbon tetrachloride injection, a model of hepatocyte regeneration in the presence of inflammatory changes; and 3) subcutaneous turpentine injection, which generates an acute phase response without hepatocyte proliferation. We demonstrated expression of GC-C mRNA in the regenerating rat liver following either partial hepatectomy or CCl4-induced hepatic necrosis. We have also shown that GC-C mRNA expression occurred in association with an acute phase reaction. Coordinate with the expression of GC-C mRNA, there was upregulation of radiolabeled STa binding to liver plasma membranes prepared from turpentine-treated rats. Maximal expression of GC-C occurred in preparations enriched for the canalicular domain. Although the function of GC-C in the liver is unknown, localization to the canalicular domain would be consistent with a role for GC-C in hepatic chloride secretion, especially in the perinatal liver and during hepatocyte regeneration.

Animals↗
PubMed1994

Utility of Gomori methenamine silver stains in bronchoalveolar lavage specimens.

Bronchoalveolar lavage (BAL) with Gomori methenamine silver (GMS) stain is commonly used to detect Pneumocystis carinii and fungal organisms as causes of infectious pulmonic disease in immunosuppressed patients. However, several reports have indicated that GMS stains are not any more sensitive than conventional cytologic stains in detecting Pneumocystis organisms in select patient populations, such as those with acquired immunodeficiency syndrome (AIDS). To examine the utility of GMS stains in our laboratory, we retrospectively reviewed 243 BALs from 188 patients. Sensitivity of the GMS stain for Pneumocystis and for fungi detection was 100%. Sensitivity for Pneumocystis and for fungi detection by Papanicolaou stain alone was 79% and 88%, respectively; by Diff-Quik stain alone it was 68% and 88%, respectively; and by combined Papanicolaou and Diff-Quik stains it was 79% and 100%, respectively. In four additional cases, fungi were detected by other methods (culture, biopsy) and not by BAL. The GMS stain result was correlated with a number of risk variables to determine which variables were associated with GMS positivity. Using stepwise logistic regression, Pneumocystis positivity by GMS stain correlated (P < 0.0001) only with the variable of history of AIDS or AIDS risk factors. Fungal organism positivity by GMS stain correlated (P = 0.02) only with the variable of history of BAL positivity for fungus. Cost savings analyses were performed, estimating the cost of the GMS stain at $45 (total cost of GMS in 243 BALs was $10,935).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Diarrheal disease. Established pathogens, new pathogens, and progress in vaccine development.

Although much progress has been made in reducing the morbidity and mortality of infectious diarrhea through the use of oral rehydration, progress in preventive measures, such as vaccine development, has been slow. Despite the plethora of candidate vaccines developed, there has not been an effective vaccine ready for general use, particularly in developing countries, during the past decade, perhaps in part because of the as-yet-undefined pathophysiology of many of these pathogens, as well as the complexity of the gastrointestinal immune system. It is hoped that more rapid progress will be made during the next decade as our understanding of these factors increases.

Animals↗
PubMed1994

Use of proliferative markers Ki-67 (MIB-1) and proliferating cell nuclear antigen (PC10) in transitional cell carcinoma of the renal pelvis.

Segmental renal resection and improved endourological techniques have resulted in conservative treatment options for transitional cell carcinoma of the renal pelvis. These techniques have increased the need for more objective measures of biological behavior. We applied two immunohistochemical markers of cellular proliferation, proliferating cell nuclear antigen (PCNA; PC10) and Ki-67 (MIB-1), to 58 archival cases of renal pelvic transitional cell carcinomas and correlated the percentage of positive cells to grade, stage, and survival, and to one another; mitotic counts (mitoses/10 high-power fields) were also performed. Expression of PCNA showed a significant difference between grades 1, 2, and 3 tumors (P = 0.05) and between superficial (Ta, T1) and invasive tumors (T2-4) (P = 0.02). There was a significant overlap, however, in the percentage of cells staining between the grades as well as the stages. PCNA staining did not correlate with survival and did not identify a subset of patients with low-stage, low-grade tumors with a poorer prognosis. The Ki-67 score exhibited a stronger correlation with grade (P = 0.001), and there was a trend of increasing Ki-67 expression with higher stage tumors, but this did not reach statistical significance (P = 0.10). Ki-67 showed comparable findings to PCNA with regard to survival and overlap in staining between the grades and stages. Mitotic counts did correlate with grade (P = 0.003) but not stage or survival. This study demonstrates that cellular proliferation, as determined by the immunohistochemical markers, Ki-67 and PCNA, is related to grade and, to a lesser extent, stage, but the use of these markers as measures of biological behavior in clinical practice may be limited.

Adult↗
PubMed1994

Technology assessment in anatomic pathology. An illustration of test evaluation using fine-needle aspiration biopsy.

Although anatomic pathology diagnoses are the standard on which treatments often are based, many facets of anatomic pathology have not been rigorously examined. These areas include the evaluation of a procedure's technical and diagnostic characteristics, clinical utility, and cost. Technology assessment is the disciplined scientific and systematic evaluation of a test or procedure, and it can be used to evaluate these areas in anatomic pathology. To illustrate and promote the use of technology assessment in anatomic pathology, we show examples in fine-needle aspiration biopsy, which is a subspecialty of cytopathology. We discuss some of the more commonly encountered problems and misconceptions of test evaluation and also the need for further fine-needle aspiration biopsy evaluation. We conclude that technology assessment is a powerful but underutilized tool for test evaluation in fine-needle aspiration biopsy and in anatomic pathology.

Biopsy, Needle↗
PubMed1994

Hematopoietic elements associated with adrenal glands. A study of the spectrum of change in nine cases.

We report nine cases of hematopoietic elements or myelolipomatous foci that were found in association with normal and neoplastic adrenal glands. A spectrum of change occurred that ranged from small clusters of purely erythroid or myeloid cells to microscopic myelolipomas that contained a mixture of hematopoietic elements. Recognition of the myeloid elements was facilitated with the use of the chloroacetate esterase (Leder) stain and a CD15 (myelomonocytic antigen) immunohistochemical stain. The majority (six of nine) of these cases were found in association with cortical adenomas in middle-aged women, but myelolipomatous foci were also found in association with an adrenocortical carcinoma, a pheochromocytoma, and a renal angiomyolipoma. The histogenesis of the foci remained speculative. However, the association with hormonally active neoplasms suggested that the hormonal microenvironment may have played a role in the development of the myelolipomatous foci.

Adrenal Gland Neoplasms↗
PubMed1993

A comparison of active compression-decompression cardiopulmonary resuscitation with standard cardiopulmonary resuscitation for cardiac arrests occurring in the hospital.

BACKGROUND: Recent studies have demonstrated improved cardiopulmonary circulation during cardiac arrest with the use of a hand-held suction device (Ambu CardioPump) to perform active compression-decompression cardiopulmonary resuscitation (CPR). The purpose of this study was to compare active compression-decompression with standard CPR during cardiac arrests in hospitalized patients. METHODS: All patients over the age of 18 years who had a witnessed cardiac arrest while hospitalized at our center were enrolled in this trial; they were randomly assigned according to their medical-record numbers to receive either active compression-decompression or standard CPR. The study end points were the rates of initial resuscitation, survival at 24 hours, hospital discharge, and neurologic outcome. Compressions were performed according to the recommendations of the American Heart Association (80 to 100 compressions per minute; depth of compression, 3.8 to 5.1 cm [1.5 to 2 in.]; and 50 percent of the cycle spent in compression). RESULTS: Sixty-two patients (45 men and 17 women) with a mean age (+/- SE) of 68 +/- 2 years were entered into the trial. Sixty-two percent of the patients who underwent active compression-decompression were initially resuscitated, as compared with 30 percent of the patients who received standard CPR (P < 0.03); 45 percent of the patients who underwent active compression-decompression survived for at least 24 hours, as compared with 9 percent of patients who underwent standard CPR (P < 0.004). Two of the 62 study patients survived to hospital discharge; both were randomly assigned to receive active compression-decompression. Neurologic outcome, as measured by the Glasgow coma score, was better with active compression-decompression (8.0 +/- 1.3) than with standard CPR (3.5 +/- 0.3; P < 0.02). CONCLUSIONS: In this preliminary study, we found that, as compared with standard CPR, active compression-decompression CPR improved the rate of initial resuscitation, survival at 24 hours, and neurologic outcome after in-hospital cardiac arrest. Larger trials will be required to assess the potential benefit in terms of long-term survival.

Aged↗
PubMed1993

Guanylin mRNA is expressed in villous enterocytes of the rat small intestine and superficial epithelia of the rat colon.

Guanylin, and endogenous ligand for the Escherichia coli heat-stable enterotoxin receptor, is a recently characterized intestinal peptide. To understand the possible physiologic function of guanylin, we examined the cellular location of guanylin mRNA expression in the rat intestine. Intestinal cells were sequentially isolated from villous tip to crypt in rat jejunum and ileum. Northern blots of total RNA identified a single 0.65 kb guanylin transcript predominantly in the villous cell fractions. In situ hybridization studies demonstrated maximal signal intensity in villous cells in rat ileum and surface epithelial cells in the colon. In the ileum, the signal was nonuniform in distribution in the surface epithelial cells, with focal areas of intense signal in clusters of columnar absorptive cells. In both colon and ileum, signal intensity was near background level in deep crypt cells, lamina propria, and muscularis.

Animals↗
PubMed1993

Multicenter trial of ionic versus nonionic contrast media for cardiac angiography. The Iohexol Cooperative Study.

Contrast agents used for cardiac angiography are different in regard to ionicity, osmolality and physiologic effects. The nonionic contrast media have been shown to have less toxic effects and a better safety profile than do higher osmolar agents. To better assess this risk, clinically stable patients undergoing cardiac angiography were stratified according to the presence of diabetes mellitus, and level of serum creatinine, and then randomized to receive either iohexol (Omnipaque 350) or sodium meglumine diatrizoate (Renografin 76). All adverse events that occurred during and immediately after angiography were tabulated. A multivariate model was used to identify patients at increased risk for adverse outcome. The 1,390 patients were randomized to iohexol (n = 696) or diatrizoate (n = 694). Significant differences were found in the number of patients with contrast media-related adverse (iohexol vs diatrizoate: 10.2 vs 31.6%; p < 0.001) and cardiac adverse (7.2 vs 24.5%; p < 0.001) events. Severe reactions and the need for treatment were more frequent with diatrizoate than with iohexol, but there was no difference in the incidence of death. The presence of New York Heart Association classification 3 or 4 and serum creatinine > or = 1.5 mg/dl predicted a higher incidence of adverse events as a result of contrast media alone. Use of iohexol is associated with a lower incidence of all types of adverse events during cardiac angiography than is diatrizoate.

Adult↗