Biomedical subjects
Publications and source records attributed to H Cohen.
Generalized juvenile polyposis usually is not associated with an increased risk for gastrointestinal carcinoma. A subgroup of patients, however, have juvenile polyps with adenomatous features. A case report of juvenile polyposis, together with adenocarcinoma of the colon and review of the literature, are presented to emphasize the potential for malignancy in this subgroup of patients and to guide appropriate evaluation.
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Preoperative serum CA-125 levels were elevated in only three of 13 patients (23%) with a pelvic mass who were found to have surgical stage I invasive ovarian adenocarcinoma. This low incidence is surprising, since elevated levels have been found in greater than 80% of patients with advanced ovarian cancer. This suggests serious limitations for using serum CA-125 levels as a screening test for ovarian cancer.
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Evidence for chronic in vivo platelet activation and hyperaggregability has been assessed in 21 renal allograft recipients. All patients received long term immunosuppression with cyclosporin (CS) and low dose prednisolone and were studied serially for 1 year post-transplantation. Spontaneous platelet aggregation in PRP was observed on 10 occasions in 5 patients. Platelet aggregation responses in PRP to low doses of ADP (0.5 and 1.0 microM) were significantly increased up to 1 year post-transplantation (p less than 0.02-less than 0.002). Total platelet nucleotide (ATP and ADP) content and release to 20 micrograms/ml of collagen were significantly decreased for 2 months post-transplantation, indicative of in vivo platelet activation (p less than 0.05-less than 0.002), and plasma PF4 levels were increased up to 1 year post-transplantation suggesting continued platelet activation of a lesser degree. Platelet sensitivity to the prostacyclin analogue Iloprost decreased after 1 month (p less than 0.05) and this persisted up to 1 year (p less than 0.01) compared with sensitivity at 1 week post-transplantation. These prothrombotic changes persisted when trough whole blood CS levels were within the therapeutic range and plasma creatinine levels were approaching or were in the normal range. These data indicate that CS-treated renal allograft recipients exhibit chronic platelet hyperactivity.
To determine the incidence and significance of Campylobacter pylori in patients undergoing routine endoscopic evaluation at this hospital, biopsies of the antrum were obtained from 132 patients and from 15 asymptomatic volunteers. Specimens were cultured and silver stained for the presence of C. pylori and were examined histologically. C. pylori was detected in 67 (51%) patients and two (13%) volunteers (P = 0.006). In patients, C. pylori was found significantly more often when the mucosa was inflamed (67%) than when the mucosa was normal (13%), and both volunteers with C. pylori had chronic gastritis on histological examination. When compared to the volunteers, patients with upper gastrointestinal symptoms had a significantly increased prevalence of antral inflammation, even if the endoscopic examination was normal. C. pylori is infrequently found in young asymptomatic adults but is found in both asymptomatic volunteers and patients in association with all forms of histological antral gastritis which is prevalent in patients with both normal endoscopic findings and peptic ulcer disease.
Serum CA 125 levels were measured preoperatively by standard radioimmunometric techniques in 89 patients with primary endometrial carcinoma before definitive surgical staging and resection. Fifty-seven of 58 (98%) patients with clinical and surgical Stage I or II disease had normal preoperative serum CA 125 levels. All eight patients with clinically advanced endometrial cancer (International Federation of Gynecology and Obstetrics Stage III or IV) had elevated CA 125 levels before surgery. Twenty of 23 patients (87%) with clinical Stage I or II endometrial cancer who were found to have extrauterine spread of disease during staging laparotomy had elevated preoperative serum CA 125 levels. Thus preoperative CA 125 levels were elevated in 28 of 31 patients (90.3%) with surgically staged endometrial adenocarcinoma with extrauterine disease and may play a useful role in detecting those patients with clinically localized endometrial cancer who have occult extrauterine spread of disease.
Prolactin (PRL) has been reported to be a possible mediator in the estradiol (E2)-induced inhibition of the pituitary-testicular axis. In order to better characterize the role of PRL, we studied the action of chronic hypoprolactinemia on this E2 inhibitory effect, using a genetically hypoprolactinemic rat (IPL nude). Normal and IPL nude adult male rats were injected either with vehicle or with E2 valerianate (4 mg/rat) once a week for 2 weeks. Rats were decapitated 7 days after the last injection. Results showed that E2 increased, similarly in both strains, pituitary weight and serum PRL levels. Serum testosterone values were reduced by 96% in both strains. However, testis weight was significantly reduced by 30% in normal rat, while in IPL nude rat, no significant decrease was observed. PRL binding sites, expressed as fmol/mg protein, were reduced in normal rat by 40%. No decrease was found in IPL nude rat. The dissociated E2 action observed in IPL nude rat suggested that only testicular growth inhibition could be mediated by PRL and confirm that testosterone level decrease could be due to a direct action of E2 on Leydig cells.
The immunosuppressive effect of deoxynivalenol (DON) was investigated in male Balb/c mice. The effect of the route of DON administration to the animals was first studied. The results showed that DON acted efficiently on the immune system per os. The administration of 100 ppm DON in the diet caused the death of all the animals within a few days. After oral administration of DON to mice, liver and kidney weights were not changed while the thymus weight was significantly reduced at concentrations greater than 10 ppm. The spleen weight was reduced less than the thymus weight. Histologically, the structure of the thymus was damaged and the high doses produced an atrophy of this organ. Serum levels of anti-sheep red blood cells (SRBC) antibodies were significantly reduced, this effect was dose-dependent. The stimulation of B and T cells by mitogens was depressed: the mitogenic responses were more reduced for thymic cells than for splenic cells. DON inhibited cellular proliferation in vitro, as estimated by [3H]thymidine incorporation:murine splenocytes were more sensitive (IC50 = 131 ng/ml of culture) than XP human fibroblasts (IC50 = 252 ng/ml of culture).
Ovine prolactin (oPRL) binding to liver membranes was studied during the estrous cycle in normal and in genetically hypoprolactinemic rats. Serum levels of hormones were measured by radioimmunoassay and prolactin (PRL) binding was determined using 125I-ovine PRL in the 100,000 X g pellet. Scatchard plots obtained were curvilinear throughout the estrous cycle in the normal rat. They were analyzed in reference to the co-operativity model and to the Hill model which give the factor delta and Hill's coefficient (nH), respectively. During the estrous cycle, delta values varied from 3.77 +/- 0.66 on the day of estrous to 13.48 +/- 1.34 on the day of proestrus at 16.00 h. At the same time, nH were 0.97 +/- 0.033 on the day of estrus and 0.72 +/- 0.025 on the day of proestrus at 16.00 h. On the other hand, the number of PRL receptors did not change significantly throughout the estrous cycle. Moreover, the dissociation of 125I-oPRL from its receptor was accelerated by the presence of native ovine oPRL. These results suggest the presence of a negative co-operativity which reached a maximum on the day of proestrus in the normal rat. This co-operativity during the estrous cycle was not found in liver from genetically hypoprolactinemic (IPL nude) rats, which present a total absence of lactation. The delta values did not vary significantly and were 6.52 +/- 1.30 on the day of estrus and 4.41 +/- 0.52 on the day of proestrus at 16.00 h. The difference between the two rat strains was statistically significant on the day of proestrus at 16.00 h for both delta and nH values.(ABSTRACT TRUNCATED AT 250 WORDS)
Ovine prolactin (oPRL) binding to liver membranes was studied during pregnancy in normal and in genetically hypoprolactinemic rats. Prolactin (PRL) binding was determined using 125I-oPRL in the 100,000 x g pellet. Scatchard plots obtained changed throughout the pregnancy in the normal rat, being almost linear from days 2 to 10, becoming curvilinear (convex) on day 16, and linear again at the end of pregnancy. They were analyzed with reference to the co-operativity and Hill models, which give delta and nH, respectively. During pregnancy, delta values varied and were respectively 2.48 +/- 0.66, 1.84 +/- 0.64, 0.52 +/- 0.06 and 1.69 +/- 0.25 on days 3, 10, 16 and 22, and the delta value on day 16 was significantly different from other days; the nH value estimated on day 16 was 1.10 +/- 0.031. These results suggest the presence of a positive co-operativity on day 16 of pregnancy. Over the same period, a huge increase in the capacity occurred on day 10 and reached a maximum on day 14. It remained elevated until the day before parturition. In the IPL nude rat, the delta value (0.92 +/- 0.45) on day 16 was significantly different from that of normal rats and indicated an absence of positive co-operativity on this day in the IPL nude rat liver. This finding was confirmed by an nH value (0.99 +/- 0.39) close to 1. The PRL-binding capacity was similar to that of normal rats, except on day 14, where it was significantly decreased. These results are discussed in relation to hormonal variations during pregnancy, particularly with regard to serum PRL and placental lactogen values.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of this study was to investigate the contribution of each cerebral hemisphere in the categorization of tactile information with and without contralateral tactile noise. Two groups of subjects rated the dissimilarity of paired stimuli varying in shape and texture presented to the left or right hand, with contralateral noise in the other hand for one group only. Analysis of variance on derived structured indices showed a general left hand advantage in the treatment of this haptic information. Moreover, a group by hand interaction revealed that noise-exposed subjects showed better differentiation of tactile information for stimuli presented to the left hand. The data suggest a unidirectional interference by the left hemisphere in the processing of tactile information in noise-free conditions and that quality of interhemispheric transfer of information may modulate cerebral functional lateralization.
Mucosal biopsies were obtained from 116 asymptomatic volunteers (50% were male; mean age, 46 years; age range, 19-91 years) to study the prevalence of duodenal gastric metaplasia (GM) and its association with inflammation and Campylobacter pylori in a normal population. GM was identified in 25 subjects (22%). Eighty-three subjects (72%) had histologic duodenitis, but in only 10 did the infiltrate include neutrophils (grade 2 duodenitis). C. pylori was found in the stomach in 36 subjects (31%), all of whom had gastritis, but was not identified histologically in the duodenum. There were no significant differences between the overall frequency of duodenitis and either GM or antral C. pylori. Although the frequency of severe (grade 2) duodenitis was not significantly different between those with and those without GM, grade 2 duodenitis was found in 9 of 36 subjects with antral C. pylori but in only 1 of 80 without antral C. pylori (P less than 0.001). These findings suggest that gastric metaplasia is a common finding in the normal population and that grade 1 duodenitis is most likely clinically unimportant, whereas grade 2 duodenitis is usually associated with antral C. pylori.
IPL (Institut Pasteur, Lyon) nude, hypoprolactinemic rats exhibit delayed puberty and a complete lack of lactation. To characterize the secretion of circulating forms of prolactin (PRL) of these rats, PRL concentrations were measured in serum and pituitaries of males and females under various physiological conditions. Two assay methods, a radioimmunoassay (RIA) and a sensitive bioassay (NB2BA) were employed. Normal rats of the Sprague-Dawley strain were tested simultaneously, as controls. The pituitary content of PRL, estimated either by RIA or by NB2BA, in IPL nude males and females was similar to that of normal male and female rats. On the contrary, serum PRL levels of IPL male rats, measured by RIA or NB2BA, were significantly reduced when compared to normal rats. In both groups, there was a close correlation between the results obtained by the two methods, the NB2BA estimates being higher. However, the NB2BA/RIA ratio was significantly decreased in serum from IPL nude rats compared to controls, indicating that the circulating form of PRL was less bioactive in this group. Castrated male rats injected with estradiol showed sharply increased PRL values as estimated by RIA or NB2BA. The increase was greater (35-fold) in IPL nude rats then in normal rats (9-fold), but these increases resulted in serum PRL levels being similar in the two groups. However, the NB2BA/RIA ratio remained significantly reduced in IPL nude rats. In female rats, PRL was measured during different physiological states: estrus, diestrus, proestrus at 1000, 1200, and 1600 h and Days 1 and 21 of gestation and 2 days postpartum.(ABSTRACT TRUNCATED AT 250 WORDS)
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A group of nine well-nourished patients, with normal serum vitamin K1 levels (mean 546, range 310-1350 pg/ml), maintained normal prothrombin times (PTs) and factor VII clotting activities throughout a 7 d course of i.v. cefotetan disodium, an N-methyl-thiotetrazole (NMTT) containing cephalosporin antibiotic. However, 11 of 20 patients, with acute intra-abdominal sepsis and initially normal PTs who underwent emergency surgery, developed prolonged PTs (INR 1.4-3.1) associated with reduction in factor VII activities (0.74-0.38 u/ml) after 3-7 d of antibiotic therapy. Nine of these 11 patients had clinical evidence of malnutrition and nine had subnormal serum vitamin K1 levels (mean 119, range 43-354 pg/ml) on admission. Seven received cefotetan but four were treated with a non-NMTT-containing cephalosporin or antibiotics belonging to other groups. The nine patients who maintained normal PTs all had normal nutritional status and normal serum vitamin K1 levels (mean 279, range 103-915 pg/ml) at presentation. The PT is a relatively insensitive indicator of vitamin K stores, and malnourished patients with low serum vitamin K1 levels are at risk of developing hypoprothrombinaemia following intravenous antibiotic therapy.
The effects of two cyclically administered, triphasic, combined low dosage oestrogen and progestogen oral contraceptives on haemostasis have been compared in a longitudinal study, over 6 months, in 26 healthy females aged 16-30 years. Subjects received either Logynon (ethinyl oestradiol and Levonorgestrol, n = 14) or SHD 415G (Schering U.K., n = 12), which contains a similar dosage of ethinyl oestradiol, but in combination with a new progestogen, gestodene. Both groups showed increases in biological activities of procoagulant factors fibrinogen, X and XII and decreased activity of the naturally occurring coagulation inhibitor antithrombin III (AT-III). The majority of these changes were statistically significant (P less than 0.05 to less than 0.001), apparent after one cycle and maintained over the six cycle period. FVII activity increased in both groups, achieving statistical significance (P less than 0.01) by cycle 6 in the SHD 415G group but not in the females receiving Logynon. Protein C activity remained unchanged in both groups. Between-group comparisons showed no differences in the procoagulant factor changes, but protein C was lower (P less than 0.05) in the SHD 415G group after three cycles of therapy. These findings indicate that both triphasic oral contraceptives Logynon and SHD 415G induce increases in procoagulant factor activities which are not balanced by increased biological levels of the two most important physiological coagulation inhibitors AT-III and protein C. These prothrombotic changes are not modified by the new progestogen, gestodene.
Hypertension patients (1781), drawn from seven large employee groups in and around New York City, were studied to determine the prevalence of resistant hypertension among them. The blood pressure criteria for resistance (potential resistance) were failure to reach and maintain a blood pressure less than 160/95 mm Hg on two separate occasions during at least 1 year of treatment. Confirmed resistance required that during the same period of follow-up, in which at least two antihypertensive agents had been prescribed simultaneously, blood pressure control had not been achieved. Potential resistance during 1 year of treatment was found in 75 patients (4.2%), and confirmed resistance for the same period was found in 52 patients (2.9%). Diastolic resistance was far more common than systolic; the systolic/diastolic resistance was the rarest of all. Of the 52 patients with confirmed resistance for the first year, 33 achieved control in subsequent years. In sum, true resistance as defined by rigorous criteria pertaining to the hypotensive effects of pharmacological intervention in the general population is exceedingly rare.