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Biomedical subjects

R Gutman

Publications and source records attributed to R Gutman.

At least 37 records · Page 2Linked to original sources

Evidence of hypothalamic-pituitary thyroid abnormalities in children with end-stage renal disease.

Patients with end-stage renal disease may have abnormalities of growth and of gonadal and thyroid hormones, so we attempted to determine the mechanisms that may be involved in the altered thyroid function. We evaluated serum thyroid hormone levels, their changes immediately after hemodialysis, the serum thyrotropin (thyroid-stimulating hormone (TSH) response to thyrotropin releasing hormone, and the circadian pattern of serum TSH in nine children with end-stage renal disease who were between 7 1/2 years and 17 years 1 month of age. Seven patients had been receiving hemodialysis for a median of 3.3 years; the other two were receiving continuous ambulatory peritoneal dialysis. Four patients had low serum total thyroxine (T4) values, and all nine had low free T4 values. Mean concentrations of total T4, free T4, and total triiodothyronine (T3), which were significantly less than normal before hemodialysis, returned to normal levels immediately after dialysis. Postdialysis thyroid hormone increases did not correlate with the decrease in weight or the increase in hematocrit observed immediately after dialysis. All but one patient had basal TSH levels within the normal range. Three patients had a deficient TSH response to thyrotropin releasing hormone, and the TSH response was prolonged in all of them. The mean (+/- SD) nocturnal TSH surge was 50 +/- 68%. Five of the eight patients studied had a nocturnal TSH surge below the normal range (95% confidence limits 47% to 300%). Serum free T4 values correlated with the TSH nocturnal surge (r, 0.73; p less than 0.05). Our findings support the hypothesis that some patients with end-stage renal disease have central hypothyroidism.

Adolescent↗

Prevalence of sexually transmitted pathogens among women attending a methadone clinic in Israel.

OBJECTIVE: To assess the prevalence of sexually transmitted pathogens in drug-addicted women in Tel Aviv, Israel. DESIGN: A prospective study conducted between March and July 1987. SETTING: A methadone clinic in Tel Aviv, Israel. SUBJECTS: Sixty four asymptomatic female drug addicts were studied; 38 of them were declared practising prostitutes. METHODS: Cervical specimens were obtained for cultures, and blood samples were drawn for serological tests. Demographic data and sexual histories were obtained using a standard questionnaire. RESULTS: Chlamydia trachomatis was detected in the cervix of 25% of women; 98% had antibody titres (greater than 1:64). Mycoplasma hominis and Ureaplasma urealyticum were isolated in 57% and 65% respectively. Gardnerella vaginalis was detected in 17% of women, and herpes simplex virus was cultured from two prostitutes. Five per cent of women were carriers of HBsAg, while 57% had HBSs and/or HBc antibodies. Only one prostitute had specific treponemal antibodies. In no case were gonococci or group B streptococci isolated, and HIV serology was invariably negative. CONCLUSION: Chlamydia and genital mycoplasmas appear to be the prevailing pathogens in Israeli drug-addicted women, while gonococci and Treponema pallidum occur only rarely.

Adult↗

Prevalence of cryptosporidiosis in Israeli children with diarrhoea.

In a prospective study, Cryptosporidium oocysts were detected in seven (3.25%) immunocompetent children with diarrhoea. The predominant clinical features were watery diarrhoea and vomiting. The patients' mean age was 19 years and infection was more common in late summer-autumn than in the rest of the year. This first survey on cryptosporidiosis in Israeli children has shown a prevalence similar to that observed in other developed countries.

Animals↗

Cultured skin fibroblasts in schizophrenia: quantitative two-dimensional electrophoresis.

Recent developments in the standardization and commercial availability of quantitative high resolution two-dimensional electrophoresis make feasible the systematic search for protein alterations characteristic of psychiatric disorders. To avoid the effects of such variables as drug intake or diet on quantitative protein makeup that might obscure its relationship to diagnosis, the investigators studied cultured fibroblasts derived from the skin biopsies of psychiatric patients. Although the method was able to resolve human fibroblast protein mixtures into 1,125 spots, no significant deviation in the quantitation of any individual spot was found to characterize the fibroblasts of patients with schizophrenia.

Adult↗

Cross resistance to ciprofloxacin and other antimicrobial agents among clinical isolates of Acinetobacter calcoaceticus biovar anitratus.

Using an agar dilution assay, for 66 of 104 (63.5%) clinical isolates of Acinetobacter calcoaceticus biovar anitratus, the MIC of ciprofloxacin was greater than or equal to 1.0 micrograms/ml. Cross resistance was demonstrable to ciprofloxacin and gentamicin (P less than 0.001), amikacin (P less than 0.01), cefotaxime (P less than 0.001), azlocillin (P less than 0.001), ceftazidime (P less than 0.001), trimethoprim-sulfamethoxazole (P less than 0.001), and minocycline (P less than 0.05). The mean MIC of ciprofloxacin for drug-susceptible isolates was consistently lower than that for resistant isolates; however, these differences were significant only for amikacin (P = 0.036).

Acinetobacter↗

Neuronal damage in the albino rat: excitotoxin, microtubule inhibitor synergism.

Separate lines of investigation implicate excitotoxins or disruption of cytoskeletal architecture in the pathogenesis of human neurodegenerative disease. To assess the hypothesis that these neurotoxic mechanisms may have a synergistic effect, albino rats were given intrastriatal administrations of either the excitotoxin, kainic acid, or the microtubule inhibitor, colchicine, or both. Assessment of neuronal damage, either by loss of neurotransmitter metabolic enzyme activities or by histologic analysis, demonstrated synergism between the agents. Further, the synergism was still apparent with substitution of quinolinic acid, but not dimethyl kainate, for kainic acid, and Vinca alkaloids, but not lumicolchicine, for colchicine.

Acetylcholinesterase↗

Antibodies against enterotoxigenic Escherichia coli in the colostrum isolated from infants with diarrhea.

The role of certain types of Escherichia coli in infectious diarrhea in infants and young children is well known. Infants who are breast-fed are less prone to gastroenteritis during their first year of life. Antibodies against three types of fimbrial antigens (adhesions) of enterotoxigenic E. coli (ETEC) in the colostrum were studied. The hemagglutination inhibition test method was used to detect antibodies against ETEC adhesions, i.e. colonization factors, I and II and fimbria type I. The colostrum of mothers on the 1st and 3rd day post partum was standard for the presence of antibodies. The results show that most of the colostrum samples contained antibodies against adhesions of the types of ETEC that we worked with. This study will enhance the knowledge as to why mothers should breast-feed their babies.

Antibodies, Bacterial↗

Schedule-dependent interaction of alpha-difluoromethylornithine and cis-diamminedichloroplatinum(II) against human and hamster pancreatic cancer cell lines.

The interaction of cis-diamminedichloroplatinum (cisplatin) and alpha-difluoromethylornithine (DFMO) has been previously shown by us to be roughly additive in enhancing the growth-inhibitory effects of cisplatin and by another group of investigators to be antagonistic. Since two different schedules of administration were used, we sought to investigate systematically the role of schedule dependence in the interaction of cisplatin and DFMO in a panel of pancreatic adenocarcinoma cell lines (PANC-1, of human origin, and WD PaCa and PD PaCa, both of hamster origin). Dose-effect relationships of single drug alone and in combination were analyzed by the median-effect principle and by the combination indices for the quantitation of synergism or antagonism with the aid of a microcomputer. Pre-cisplatin administration of DFMO for 2 or 5 to 6 days at concentrations of 50 or 100 micrograms/ml (0.21 or 0.42 mM) was found to antagonize the effects of cisplatin to various degrees in the cell lines. In contrast, whenever post-cisplatin DFMO was administered, marked enhancement, which was synergistic in most instances, of cisplatin's inhibition of colony formation was found. Thus, the interaction of cisplatin and DFMO is felt to be schedule dependent with deleterious effects found only when DFMO is administered prior to and not following cisplatin. Furthermore, the combination shows promise as an approach to overcoming drug resistance in pancreatic cancer.

Adenocarcinoma↗

Cultured skin fibroblasts in schizophrenia: acute growth and susceptibility to damage.

The study of cultured fibroblasts derived from skin biopsies of patients with inherited neurodegenerative disorders has aided in the elucidation of their pathological basis. This usefulness might be expected to extend to the study of fibroblast characteristics in schizophrenia in view of recent evidence of neurodegenerative changes in the disorder. In this study, the acute growth characteristics and response to toxic oxygen metabolites of fibroblast cell lines derived from skin biopsies of patients with schizophrenia (n = 9) are compared with those derived from psychiatric patients with various diagnoses not associated with a deteriorating course (controls = 11). No significant differences between the cell lines of the two patient groups are found.

Adult↗

Combined effects of alpha-difluoromethylornithine and doxorubicin against pancreatic cancer cell lines in culture.

Pancreatic adenocarcinoma presents a clinical and experimental challenge because of its relative resistance to conventional modes of therapy. The present study explores a novel, biologically based approach to enhancing its chemosensitivity and to overcoming its chemoresistance in a panel of pancreatic adenocarcinoma cell lines (two human lines: PANC-1 and COLO-357; and two hamster lines: WD PaCa and PD PaCa). Difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase (ODC) that produces antiproliferative effects by polyamine depletion, was combined with the cytotoxic agent doxorubicin (DOX) in vitro. The inhibitory effects of DFMO were cytostatic and roughly additive to those of DOX. Although the response to the combination varied as a function of the cell lines studied and the response to DFMO as a single agent, all cell lines studied showed some increased inhibition with the combination. The most striking enhancement was seen in our most DOX-resistant cell line, WD PaCa, and also in PANC-1, a relatively sensitive cell line. Thus, the combination of DFMO and DOX shows promise as an experimental approach to the problem of drug resistance and the limited chemosensitivity of pancreatic cancer.

Adenocarcinoma↗

The propriety of narcotic usage in hospitalized patients.

The propriety of narcotic usage at the Hadassah Hospital has been studied in 35 cancer patients and 70 post-operative patients. Eighty-three per cent of the cancer patients and 66% of the surgical patients remained in moderate to severe distress in spite of the analgesic therapy. Insomnia and anxiety, plus depression in the cancer patients, were the major results of uncontrolled pain. The inadequacy of the treatment was attributed to the incorrect selection of medication, usage "as needed' policy and smaller daily doses than advocated. This resulted mainly because of exaggeration of the risk of tolerance and addiction by both patients and personnel.

Drug Utilization↗

Combined FSH and LH secreting pituitary adenoma in a young fertile woman without primary gonadal failure.

A 28 year old fertile woman presented with a history of amenorrhoea and galactorrhoea, and an enlarged pituitary fossa. Serum FSH and LH were repeatedly elevated both basally (32 and 44 mIU/ml) and after LRH (peak values, 108 and 420 mIU/ml). One mg of oestradiol (E2) benzoate im daily for 5 days failed to lower basal or LRH-stimulated serum gonadotrophins. Serum E2 was 170 pg/ml, basal serum prolactin (Prl) was 30 ng/ml and responded briskly to TRH (peak value 103 ng/ml). An 0.8 X 0.8 cm tumour was selectively excised by transsphenoidal surgery. Menses reappeared soon afterwards accompanied by normalization of serum FSH and LH plus biochemical evidence of ovulation. Specific immunostaining of tumoural cells was achieved with either FSH or LH antiserum, and adequate suppression of staining was obtained after preabsorbing each antiserum with and excess of its respective antigen. Our patient appears to be the first documented female with a combined FSH and LH producing pituitary tumour and no prior evidence of primary gonadal failure.

Adenoma↗

Mycoplasma pneumoniae is a frequent cause of exacerbation of bronchial asthma in adults.

The possible role of infection with Mycoplasma pneumoniae (MP) in exacerbation of bronchial asthma in adults was studied in 95 patients hospitalized due to acute asthma. Twenty (21%) of these patients had evidence of a recent MP infection as determined by the presence of high levels of MP-specific IgM antibodies. In addition, high levels of both IgM and IgG but not IgA serum immunoglobulins were observed in the MP-infected group as compared to a control group of 20 non-MP-infected asthmatics. Five out of 20 MP-infected asthmatics exhibited rheumatoid factor (RF) in their sera while patients in the control group were all negative for RF. It is concluded that MP infection may be significant in exacerbation of asthma in adults.

Adolescent↗

Effect of brominated vegetable oils on heart lipid metabolism.

Normal rats fed for 105 days on an experimental diet made up of standard laboratory chow supplemented with 0.5% of a mixture of brominated sunflower-olive oil (BVO) developed a significant increase in the triacylglycerol content of the heart, liver and soleus muscle compared to controls. In addition, BVO-treated rats had a decrease in plasma levels of triacylglycerol and total and HDL cholesterol. Plasma fatty acid levels and plasma post-heparin lipolytic activities, such as H-TGL, LPL, T-TGL and MGH were similar to those of control animals fed the standard chow alone. Heart PDHa (active portion of pyruvate dehydrogenase) was dramatically decreased in the BVO-fed rats. A faster rate of spontaneous lipolysis was recorded in the isolated perfused preparation of hearts from the experimental animals. The addition of 10(-7) M of glucagon to the perfusate, however, revealed a lipolytic effect comparable to the one observed in the control rats. In summary, our findings of normal fatty acids and low triacylglycerol plasma levels associated with normal activities of the various PHLA (post-heparin lipolytic activity) enzymes suggest that accumulation of triacylglycerol in heart muscle may not be explained essentially in terms of an elevated uptake and/or increased delivery of plasma fatty acids or plasma triacylglycerol. A decreased in situ catabolism of tissue triacylglycerol also appears unlikely because the spontaneous as well as the glucagon induced lipolysis in the heart both were found to be unimpaired.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of tiadenol and clofibrate on plasma post heparin lipolytic hepatic, extrahepatic and monoglyceride hydrolase activities in rats with hypertriglyceridemia induced by a sucrose rich diet.

Normal rats fed an isocaloric sucrose-rich diet (SRD) for 3 weeks developed high levels of triacylglycerol in plasma (P) (mmol triacylglycerol I-1) heart (H) and liver (L) tissues (mumol triacylglycerol mg DNA-1) as compared to control rats fed the standard chow (STD) (X +/- SEM; P: SRD 1.32 +/- 0.06 vs STD 0.49 +/- 0.05, P less than 0.001; H: SRD 2.1 +/- 0.17 vs STD 0.94 +/- 0.01, P less than 0.001; L: SRD 8.48 +/- 1.47 vs STD 1.71 +/- 0.12, P less than 0.001). A simultaneous drop in the activities (mumol glycerol ml-1 hr-1) of several plasma post heparin lipolytic enzymes was observed; total triglyceride lipase (T-TGL): SRD 5.32 +/- 0.34 vs STD 7.48 +/- 0.64, P less than 0.01; lipoprotein lipase (LPL): SRD 1.61 +/- 0.26 vs STD 2.42 +/- 0.41, P less than 0.05; hepatictriglyceride lipase (H-TGL): SRD 3.71 +/- 0.28 vs STD 5.05 +/- 0.69, P less than 0.05 and monoglyceride hydrolase (MGH) (mumol glycerol I-1 min-1): SRD 558 +/- 108 vs STD 1165 +/- 45, P less than 0.001. Rats fed the SRD presented glucose intolerance after i.v. glucose (Kg X 10(-2); 1.06 +/- 0.09 vs 2.61 +/- 0.14 of STD, P less than 0.001) in spite of the presence of hyperinsulinism (sigma plasma IRI microU/ml from 0 to 30 min: 184.6 +/- 23.6 vs 100.5 +/- 9.7 of STD, P less than 0.01) suggesting that a state of insulin resistance had developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Diazoxide prevents the development of hormonal and metabolic abnormalities present in rats fed a sucrose rich diet.

We have previously reported that normal Wistar rats fed an isocaloric, sucrose-rich (63%) diet (SRD) developed glucose intolerance and elevated triglyceride levels in plasma (P) as well as in heart (H) and liver (L) tissue. This metabolic state was accompanied by hyperinsulinism both in vivo and in vitro, suggesting that a state of insulin resistance has developed. In order to gather information on the role of hyperinsulinemia and glucose intolerance in the development of the above lipid metabolism abnormalities, diazoxide, a known insulin release blocking agent was administered (120 mg/kg/day) together with the diet (SRD + DZX) for 22 days. Control groups fed a standard chow (STD) or the STD plus diazoxide (STD + DZX) were included in the study. Under the present experimental design, DZX was able to prevent the development of hyperinsulinism, glucose intolerance and elevated levels of triacylglycerol in plasma, heart and liver present in animals fed on a sucrose rich diet. Our results suggest that mechanisms involved in the development of this nutritionally induced syndrome may include an interaction of hyperinsulinemia, with a direct effect of sucrose on several steps of lipid metabolism.

Animals↗