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Biomedical subjects

S M Cohen

Publications and source records attributed to S M Cohen.

At least 163 records · Page 9Linked to original sources
PubMed1994

neu is not involved in N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced bladder carcinoma or 2-amino-4-(5-nitro-2-furyl)thiazole transformation of rat bladder epithelial cells.

Enhanced c-erbB-2/neu expression has been linked with a poor prognosis in human bladder cancer. Previous reports have shown that a point mutation at nucleotide T2012 in the coding region of the transmembrane domain of the rat gene is sufficient to confer transformation potential on this gene. We examined the comparative levels of p185neu as well as the sequence around the hotspot (T2012) of the neu gene of rat bladder cells transformed by 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) or established in culture from N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT)-induced rat bladder tumors. We concluded that increased p185neu expression did not correlate significantly with tumorigenicity. No alterations in nucleotide sequences of the neu gene were observed in either in vitro model.

Animals↗
PubMed1994

Neu is not involved in N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide- induced bladder carcinoma or 2-amino-4-(5-nitro-2-furyl)thiazole transformation of rat bladder epithelial cells.

Enhanced c-erbB-2/neu expression has been linked with a poor prognosis in human bladder cancer. Previous reports have shown that a point mutation at nucleotide T2012 in the coding region of the transmembrane domain of the rat gene is sufficient to confer transformation potential on this gene. We examined the comparative levels of p185neu as well as the sequence around the hotspot (T2012) of the neu gene of rat bladder cells transformed by 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) or established in culture from N-[-4-(-5-nitro-2-furyl)-2- thiazolyl]formamide (FANFT)-induced rat bladder tumors. We concluded that increased p185neu expression did not correlate significantly with tumorigenicity. No alterations in nucleotide sequences of the neu gene were observed in either in vitro model.

3T3 Cells↗
PubMed1994

Prohibitin gene is overexpressed but not mutated in rat bladder carcinomas and cell lines.

Prohibitin was isolated as a candidate antiproliferating gene in rat liver cells, and it has been suggested as a tumor suppressor gene in human breast cancer. We investigated the steady state level of prohibitin mRNA in rat bladder cell lines and in rat bladder carcinoma induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) and sodium saccharin, as well as the protein level in rat bladder epithelial cells. We also examined the prohibitin gene for mutations using the polymerase chain reaction (PCR) single strand conformation polymorphism (SSCP) and direct sequencing methods. All rat bladder tumors investigated and several cell lines had unexpectedly increased steady state levels of prohibitin mRNA compared with that of normal rat bladder or liver. The prohibitin protein was easily detected by Western blotting in all cell lines regardless of their malignant status or growth rate. However, PCR-SSCP and direct sequencing analysis showed no mutations in the prohibitin gene. These results These results indicate that prohibitin overexpression, but not mutations, may be involved in the early stage of rat bladder carcinogenesis.

Animals↗
PubMed1994

A comparison of the effects of sodium saccharin in NBR rats and in intact and castrated male F344 rats.

High doses of sodium saccharin (NaSac) increase proliferation in the bladder of the rat, with a male preponderance. The possibility that alpha 2u-globulin is involved in its mechanism of action was evaluated by feeding it at 7.5% of the diet to NCI-Black-Reiter (NBR) male rats, which do not synthesize liver-derived alpha 2u-globulin. NaSac affected urinary parameters similarly in F344 and NBR male rats, but NBR rats consumed more water leading to greater urinary volume. NaSac produced less proliferation in NBR than in intact F344 rats, with intermediate changes in castrated F344 males, which had intermediate urinary alpha 2u-globulin levels.

Alpha-Globulins↗
PubMed1994

Mutations and expression of the p53 gene in rat bladder carcinomas and cell lines.

Abnormalities of the p53 gene are frequently observed in human tumors, including urinary bladder carcinoma, suggesting that p53 plays an important role in human carcinogenesis. However, its role in rat bladder carcinogenesis is unclear. We investigated p53 gene mutations and expression in rat urinary bladder carcinogenesis in vivo and in vitro. Fifteen urothelial cell lines, including six untransformed (nontumorigenic) ones, six transformed (tumorigenic) in vitro, and three derived from tumors induced in vivo, were examined for p53 expression by immunochemical analysis and for p53 mutations; in addition, 81 rat bladders were analyzed immunohistochemically for p53 expression, and 23 rat bladder tumors were analyzed for p53 mutations. Four cell lines had mutations in the p53 gene. Two of these were missense point mutations, and the other two were splicing mutations. On the other hand, no mutations were found in the bladder tumors induced in rats. By immunoprecipitation with PAb240, which is supposed to be specific for mutant p53, we detected mutations in three of the cell lines; PAb240 did not react with wild-type p53. However, in all cell lines and in growing populations of primary cultured bladder urothelial cells, p53 expression was detected immunohistochemically or by western blotting using PAb240 or PAb 421 monoclonal antibodies. In a high percentage of transitional cell carcinomas, wild-type p53 expression was detected by immunohistochemical analysis with PAb240. These results suggest that p53 gene mutations may not occur frequently in rat bladder carcinogenesis in vivo but may occur in vitro and that p53 overexpression detected immunohistochemically is common and may be related to cell proliferation rather than to the presence of mutations in rat bladder carcinogenesis.

Animals↗
PubMed1994

31P NMR and triple quantum filtered 23Na NMR studies of the effects of inhibition of Na+/H+ exchange on intracellular sodium and pH in working and ischemic hearts.

The triple quantum filtered 23Na NMR method is applied here to measure the effects of EIPA, a specific inhibitor of the Na+/H+ antiporter, on relative intracellular sodium concentrations in isolated working hearts at baseline, during ischemia, and at subsequent reperfusion. In analogy to the spectrophotometric isosbestic point, an approach is developed that defines a value of tau at which the effect of the relaxation times on the TQF signal intensities is minimized, and the signals are proportional to the sodium concentration for both ischemic and working hearts. EIPA at 1.5 microM significantly inhibited (P < 0.01) the influx of intracellular Na+ during 20 min of ischemia at 36.2 degrees C in this rat heart model. In parallel 31P NMR studies, EIPA had no effect on either the development of acidosis during ischemia or on the recovery of pHi during reperfusion despite its profound effect on intracellular Na+ influx. Thus, under our conditions the Na+/H+ antiporter did not play a critical role in the maintenance of intracellular pH. EIPA treatment resulted in improved recovery (P < 0.005) of mechanical function after 20 min of ischemia. [ATP] was higher in treated hearts during ischemia and reperfusion.

Acidosis↗
PubMed1994

Does laparoscopic-assisted ileal pouch anal anastomosis reduce the length of hospitalization?

Previous data have suggested that laparoscopic colon and rectal surgery may shorten the length of hospitalization. These claims have been attributed to a reduction of the length of ileus. The definition of "ileus" is variable and in all cases is subjective. In this study it was defined as the length of time until the patient passed flatus or stool without nausea, vomiting or abdominal distention. This prospective study was undertaken to compare the duration of ileus and of hospitalization after laparoscopic-assisted (LAC) and standard laparotomy (SC). After restorative proctocolectomy with an ileal-pouch anal anastomosis (IPAA) in both sets of patients. Twenty-two patients underwent LAC and 20 age, sex, and diagnosis-matched controls underwent SC. Mucosal ulcerative colitis (MUC) was the diagnosis in 16 LAC and in 15 SC patients while polyposis was the diagnosis in 6 LAC and in 5 SC patients. The mean time to resolution of postoperative ileus was 4.2 (4-11) days in the LAC group and 3.3 (2-5) days in the SC group. Hospital discharge was similar in each group occurring at a mean of 8.7 (7-13) days after LAC and 8.9 (6-18) days after SC. Neither the length of time for ileus resolution nor the length of hospitalization were reduced in the LAC group. Laparoscopic-assisted IPAA conferred none of the theoretical advantages associated with other laparoscopic procedures.

Adolescent↗
PubMed1994

The diagnosis of anal ulcers in AIDS patients.

Recent reports have suggested that routine microscopic evaluation of anal ulcer tissue from AIDS patients is not the most accurate way to diagnose viral infection. This study was undertaken to determine if either viral culture (VC) or immunohistochemistry (IHC) can improve the diagnostic accuracy as compared with routine hematoxylin and eosin (H&E) staining. Specifically, we sought to identify inclusion bodies of cytomegalovirus (CMV) or herpes simplex virus (HSV) to assist in the diagnosis of CMV or HSV. All patients had clinical evidence of an anal ulcer or a nonhealing anal fissure. Duration of symptoms ranged from 1 week to 3 months with a mean of 6 weeks. All specimens were submitted for viral culture in addition to routine H&E staining; immunohistochemistry was also performed. Twenty-five paraffin-embedded anal ulcer biopsies from 23 male patients (age range 27-73; mean 37.4 years) with the diagnosis of AIDS or AIDS-related complex (ARC) were reviewed over a 4 year period (1988-1992). Routine H&E staining revealed 6 (22%) specimens with CMV inclusions. Four of these 6 reacted positively with IHC (67%) and one was positive on viral culture (17%). In the remaining 19 specimens that did not reveal infection with CMV (78%), IHC was positive in 2 patients (10%) and viral culture was positive in 1 patient (5%). Although HSV was not seen in any of the specimens on H&E staining, IHC was positive in one patient (3.5%) and viral culture reacted positively in 8 (29%) specimens. Thus IHC is a good confirmatory test for CMV inclusions and can be used to achieve a definitive diagnosis in equivocal cases.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1994

An initial comparative study of two techniques of laparoscopic colonic anastomosis and mesenteric defect closure.

Laparoscopic colon and rectal surgery is still in its nascent stages of development. The ease, efficacy, and safety of intracorporeal mechanical colonic anastomosis are contingent upon expensive stapling devices. Although mobilization and mesenteric division are feasible, a method of inexpensive rapid anastomosis is not. A single inexpensive multifire stapler which could be used both to fashion the anastomosis and to close the mesenteric defect would be ideal. Therefore, this prospective randomized study was undertaken to compare the clinical and functional results of laparoscopic colotomy closure performed using the Endopath EMS hernia stapler (EMS; Ethicon Endosurgery Inc., Cincinnati, OH) to results of using standard two-layer hand suturing (HS). Both the colotomy itself and the mesenteric defect closure sites were included in the randomization and analysis. The abdominal cavity was assessed for evidence of anastomotic leakage, abscess, and adhesion formation. In addition, radiographic luminal diameter, bursting strength, and histology were evaluated. Eight healthy pigs were randomized to either the EMS (N = 4) or HS (N = 4). There was no evidence of leakage, abscesses, or adhesion formation in either group; however, the mesenteric defect revealed more scarring in the HS than in the EMS animals. There were no significant differences in either luminal diameter (HS: mean = 0.92 cm; EMS: mean = 0.91 cm) or bursting strength (HS: mean = 171 mm Hg; EMS: mean = 157 mm Hg) (P > 0.05). Histologic analysis also demonstrated no difference in inflammation, necrosis, or fibrosis. This study suggests that this technique can be safely applied to both colotomy closure and mesenteric defect repair.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1994

Must early postoperative oral intake be limited to laparoscopy?

PURPOSE: This prospective, randomized study was designed to evaluate whether or not early postoperative feeding (claimed as a unique benefit of laparoscopic surgery) is possible after laparotomy and colorectal resection. METHODS: The trial was performed between July 1, 1992 and October 31, 1992 and included all 64 consecutive patients who underwent laparotomy with either a colonic or an ileal resection. In all cases the nasogastric tube was removed immediately after the operation. Group 1 consisted of 32 patients (age range, 15-81 years; mean, 52 years) who received a regular diet on the first postoperative morning. Group 2 consisted of 32 patients (age range, 15-87 years; mean, 52 years) who were fed in a traditional manner. Regular food was permitted after resolution of ileus as defined by resumption of bowel movements in the absence of abdominal distention, nausea, or vomiting. RESULTS: The rate of nasogastric tube reinsertion for distention with persistent vomiting was 18.7 percent (six patients) in Group 1 and 12.5 percent (four patients) in Group 2. Although vomiting was experienced more frequently by patients in Group 1 (44 percent vs. 25 percent, respectively), there was no difference between the two groups with regard to the duration of postoperative ileus (3.6 vs. 3.4 days, respectively). In the 26 patients from Group 1 who did not require nasogastric tube reinsertion, there was a trend toward shorter hospitalization (6.7 vs. 8.0 days, respectively). CONCLUSION: Early oral intake is possible after laparotomy and colorectal resection. Thus, the laparoscopic surgeon's claim of early tolerated oral intake may not be unique to laparoscopy.

Adolescent↗
PubMed1994

Prospective, randomized, endoscopic-blinded trial comparing precolonoscopy bowel cleansing methods.

PURPOSE: Recent reports have suggested that precolonoscopy bowel preparation is easier to tolerate if a small volume solution is used. Therefore, the aim of this study was to compare three oral solutions for colonoscopy to determine any changes in either patient compliance or cleansing ability. METHODS: Four hundred fifty patients were prospectively randomized to receive either a standard 4-liter polyethylene glycol solution, a newer sulfate-free 4-liter polyethylene glycol solution, or a 90-ml oral sodium phosphate preparation. Before and after bowel preparation all patients were weighed, and serum electrolytes as well as phosphate, magnesium, calcium, and osmolarity were measured. In addition, a detailed questionnaire was used to assess side effects and patient satisfaction. Endoscopists blinded to the type and quantity of preparation used scored the type of residual stool and the percentage of bowel wall visualized for each segment of colon and for the overall examination. Nurses recorded all procedure times as well as the quantity of irrigation and aspiration. RESULTS: Four hundred twenty-two age-matched and sex-matched patients completed all phases of the trial. There were no clinically significant changes in weight or in any biochemical parameters. There was, however, asymptomatic hyperphosphatemia in the sodium phosphate group (P < 0.01). The length of time to the cecum was similar for all three groups, with a higher volume of fluid suctioned for sodium phosphate (P < 0.01). Overall, endoscopists scored sodium phosphate as "excellent" or "good" in 90 percent vs. 70 percent and 73 percent after the polyethylene glycol or sulfate-free lavage, respectively (P < 0.01). Particulate or solid stool was found in all segments of the colon more frequently after both large volume preparations than after sodium phosphate (P < 0.05). There were no significant differences in the frequency or intensity of any of the 11 side effects questioned. Eighty-three percent of the patients who received the sodium phosphate preparation stated they would take this same preparation again, vs. only 19 percent and 33 percent for polyethylene glycol and the sulfate-free lavage, respectively (P < 0.01). CONCLUSION: The smaller volume oral sodium phosphate was not associated with any clinically significant problem, caused no increase in the incidence of side effects, was preferred by patients, and was more effective in colonic cleansing. However, the hyperphosphatemia seen may limit its use in patients with impaired renal function.

Adolescent↗
PubMed1994

Glandular stomach hemorrhage induced by high dose saccharin in young rodents.

In studies primarily designed to evaluate the effects of saccharin and silicate on the urinary bladders of rodents, hemorrhage of the glandular stomach was observed in high incidence. It occurred in young rats with high doses of saccharin (7.5% sodium saccharin; 6.3% acid saccharin), with no difference between male and female F344 rats fed during ages 5 to 15 weeks. no difference between sodium saccharin and acid saccharin, and was reversible, even with continued saccharin administration. Sodium silicate (0.38, 1.13, 2.26% of the diet) had no influence on gastric hemorrhage. Iron deficiency anemia has been observed in young rats fed high dietary levels of saccharin, and the present results suggest that gastric hemorrhage contributes to its etiology.

Animals↗
PubMed1994

Mitogenic effects of propoxur on male rat bladder urothelium.

Propoxur produces bladder tumors in rats, but not other species. The hyperplastic and tumorigenic effects do not occur if urinary pH is lowered by administering propoxur in a semi-synthetic diet or co-administering it with ammonium chloride (NH4Cl). We fed propoxur at 8000 p.p.m. in Altromin 1321 diet to male Wistar rats for 4 weeks, with or without NH4Cl as 10,000 p.p.m. of the diet. The urine of rats fed control diet with or without propoxur had a relatively high urinary pH (approximately 8); the addition of NH4Cl lowered the urinary pH by approximately 0.5-1.0 units. There was no evidence of urinary calculi or amorphous precipitate nor was there an increase in microcrystals or formation of different crystals than occur in normal rat urine. Propoxur produced hyperplasia of the urothelium, as observed by light and scanning electron microscopy, and increased the labeling index for proliferating cell nuclear antigen. These effects were significantly inhibited by co-administration with NH4Cl. There was no evidence of urothelial necrosis. Thus, the hyperplasia appears to result from a direct mitogenic effect of propoxur or a metabolite on the urothelium, rather than from toxicity and consequent regeneration. Based on the present study and previous investigations, the urothelial effects of propoxur in the rat are dependent on high urinary pH and high administered doses, factors which need to be incorporated into any mechanistic model for the chemical and into any extrapolation to potential effects in humans.

Animals↗
PubMed1994

p53 mutation is infrequent and might not give a growth advantage in rat bladder carcinogenesis in vivo.

Abnormalities of the p53 gene are frequently observed in human tumors, including urinary bladder carcinoma, suggesting that p53 plays an important role in human carcinogenesis. However, its role in rat bladder carcinogenesis is unclear. In this study, we investigated the presence of p53 mutations in 122 urinary bladder tumors induced in F344 rats in the following carcinogenesis models: (i) 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT; 6 weeks) in the diet followed by 3% or 5% sodium saccharin in the diet, 5% sodium ascorbate, 3.12% calcium saccharin (CaSac), 1.34% sodium chloride (NaCl), 5.2% CaSac plus 1.34% NaCl, or basal diet alone (72 weeks); and (ii) 0.2% FANFT, 0.05% N-(4-hydroxybutyl)nitrosamine in the drinking water, N-methyl-N-nitrosourea 20 mg/kg body wt, i.p. twice per week, or basal diet alone (4 weeks), followed by 3% uracil in the diet (20 weeks). Polymerase chain reaction-single-strand conformation polymorphism analysis and direct sequencing were performed for exons 5-8 in the rat p53 gene. We found nine tumors (7.4%) with p53 mutations. Two tumors had two mutations in the p53 gene. The tumors that had p53 mutations were relatively smaller than those that did not have p53 mutations. There were no mutation clusters among the treatments or hot-spots for p53 mutations. These results indicate that p53 mutation is infrequent in bladder carcinogenesis in rats, and when it does occur, it does not appear to provide a growth advantage.

Animals↗
PubMed1994

Development of a test of cognitive bias in medical decision making.

PURPOSE: To develop an inventory to measure the influence of cognitive biases on medical decisions. METHOD: The Inventory of Cognitive Biases in Medicine (ICBM) consists of 22 medical scenarios in which respondents choose between alternatives that represent bias-prone or statistically based decisions. In 1992 and 1993 the ICBM was administered to 102 medical students and residents and 318 physician faculty at the Wright State University School of Medicine. RESULTS: The statistically correct decision was made in fewer than half the ICBM scenarios for both groups (students and residents, 41%; faculty, 49%); and only the faculty scored better than chance. Acceptable reliability (KR 20 = .62 for the faculty administration) and item discrimination (mean = .49) were achieved. Further, the results suggest that the ICBM has both content and construct validity. CONCLUSION: The rather poor performances of the students and residents and the faculty on the ICBM suggest that cognitive biases constitute an important detraction from reliance on logical and statistical strategies. The ICBM shows promise for use as a tool in both instructional and research endeavors attempting to minimize and elucidate this phenomenon.

Cognition↗