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Biomedical subjects

R Gutman

Publications and source records attributed to R Gutman.

At least 19 recordsLinked to original sources

Effect of therapy with a new glucocorticoid, deflazacort, on linear growth and growth hormone secretion after renal transplantation.

Deflazacort is an oxazoline compound derived from prednisolone with similar antiinflammatory effects but fewer side effects. We studied changes in kidney function, growth velocity, weight/height ratio, and growth hormone secretion before and a year after substitution of deflazacort for methylprednisone in nine patients aged 9 to 15 years, 4 years after renal transplantation; all were in Tanner pubertal stage 1. Methylprednisone (mean +/- SEM: 0.2 +/- 0.02 mg/kg per day) was replaced by deflazacort (0.3 +/- 0.03 mg/kg per day) for a mean period of 15 months. Serum creatinine and calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 1.5 +/- 0.3 to 3.2 +/- 0.5 cm/yr (p < 0.005) in the nine patients. Weight/height ratio decreased from 28.4% +/- 8.5% to 16% +/- 6.7% (p < 0.005). Cushingoid appearance decreased in all patients. Mean spontaneous growth hormone secretion increased from 2.5 +/- 0.4 to 4.4 +/- 1.2 ng/ml (p < 0.05). Our findings indicate that immunosuppressive treatment with deflazacort is as effective as methylprednisone and is associated with fewer side effects.

Body Height

"In vitro" effects of insulin on the PDH complex of the isolated perfused heart of rats fed a sucrose-rich diet.

We have recently reported that the "in situ" myocardial concentrations of the active form of the Pyruvate Dehydrogenase Complex (PDHa) were significantly decreased in hearts obtained from normal rats fed for 3 weeks on an isocaloric sucrose rich (63%) diet (SRD) when compared to age matched controls fed on the standard laboratory chow (STD). Since, on the one hand SRD rats present glucose intolerance and impaired "in vivo" insulin action and, on the other hand the effects of insulin on the interconversion of heart PDH remains a controversial matter, we found it relevant to study the effects of insulin on the PDH complex in the "in vitro" perfused (Langendorff technique) heart preparations obtained from SRD rats. After a 35 minute perfusion period with 5.5 mM glucose as the only nutrient in the perfusate, PDHa as a percentage of total PDH was found to remain significantly lower in SRD hearts (M +/- SEM 32.6 +/- 2.3) when compared to STD hearts (68.3 +/- 4.6, P less than 0.05) in spite of comparable total PDH activities in both groups of animals. Although the addition of insulin to the perfusate (20 mu/ml) resulted in a significant increase in the percentage of PDHa (45.8 +/- 3.4) of SRD heart, values attained still remained significantly lower than those obtained in STD controls (67.5 +/- 3.6; P less than 0.05). Simultaneously, the addition of insulin to the perfusate, significantly reduced the Acetyl-CoA/CoASH ratio in SRD hearts although this ratio remained still much higher than those observed in STD controls under the same experimental conditions.

Acetyl Coenzyme A

Peritonitis caused by Pseudomonas putrefaciens in patients undergoing continuous ambulatory peritoneal dialysis.

Three cases of peritonitis caused by Pseudomonas putrefaciens in patients undergoing continuous ambulatory peritoneal dialysis are described. In two cases asymptomatic colonization of the dialysate preceded overt infection. All patients responded successfully to standard antibiotic therapy with gentamicin or ofloxacin. This is the first report of peritonitis caused by P. putrefaciens.

Aged

Biochemical abnormalities in the heart of rats fed a sucrose-rich diet: is the low activity of the pyruvate dehydrogenase complex a result of increased fatty acid oxidation?

We have previously shown that normal Wistar rats fed for 3 weeks with an isocaloric sucrose-rich (63%) diet (SRD) develop high levels of plasma free fatty acids and increased triacylglycerol content in the myocardium. We are now reporting that these changes are accompanied by remarkably low levels of the active form of the pyruvate dehydrogenase complex (PDHa; mean +/- SEM, 37.2% +/- 3.7% of the total activity) when compared with levels found in hearts donated by control rats fed the standard chow diet (STD; 71.0% +/- 2.8%; P less than .01). Increased concentrations of both long-chain acyl-CoA (0.21 +/- 0.03 v 0.06 +/- 0.01 mumol.g dry weight-1 found in STD; P less than .01) and acetyl-CoA (0.17 +/- 0.05 v 0.09 +/- 0.01 found in STD; P less than .01), as well as a relative decrease in coenzyme A (CoASH) (0.21 +/- 0.02 v 0.32 +/- 0.05 from STD; P = NS), resulting in an increased acetyl-CoA/CoASH ratio (0.80 +/- 0.13 v 0.29 +/- 0.03 in STD; P less than .01) may have stimulated the PDH kinase, leading in turn to an inactivation of the PDH complex. The above enzymatic and metabolic changes in the in situ heart of SRD-fed rats were still present after perfusing them for 35 minutes with a Krebs-Henseleit buffer containing 11 mmol/L glucose as the only exogenous substrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl Coenzyme A

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