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Biomedical subjects

M Kremer

Publications and source records attributed to M Kremer.

At least 109 records · Page 6Linked to original sources

[Plasma renin activity and prostaglandin E2 in hypotension induced by sodium nitroprusside].

Sodium nitroprusside (SNP) is a potent, effective and readily reversible vasodilating agent frequently used in anaesthesia for deliberate hypotension. Moderate hypotension induced by SNP activated catecholamine and vasopressin secretions, and the renin-angiotensin system, resulting in partial antagonism of the hypotensive response to SNP. Furthermore, this increase in renin release was involved in the hypertensive rebound after SNP withdrawal. This activation of vasoconstrictor systems led to pharmacological associations aimed at reducing the risk of cyanide poisoning. The physiological interrelationship between prostaglandins and renin secretion has now been well established but, as far as we know, no paper existed concerning prostaglandins during SNP-induced hypotension. In such hypotension (Pa: -30%), monitored by invasive and non invasive haemodynamic techniques (pulsed Doppler), the variations in plasma renin activity (PRA) and in venous and arterial plasma PGE2 concentrations (V PGE2 and A PGE2), determined by radioimmunoassay, were studied in anaesthetized dogs. Invasive haemodynamic data were similar to previous reports. Common carotid diameter increased (p less than 0.05), with a constant common carotid blood flow. PRA (p less than 0.05), V PGE2 (p less than 0.05) and A PGE2 (p less than 0.05) increased. PRA and V PGE2 were highly correlated before and after SNP. SNP resulted in hypotension with reflex sympathetic activation and dilatation of large arteries. Carotid blood flow autoregulation was maintained. Whilst pulmonary removal of PGE2 remained unchanged, an increase in A PGE2 may have been involved in the vasodilator mechanisms.

Animals↗

Onchocerciasis in Israel.

A 15-year-old boy with onchocerciasis had severe generalized pruritus of five months' duration. He had been born and raised in Ethiopia and had emigrated to Israel one year earlier. A biopsy specimen of an area of depigmentation on the right thigh disclosed microfilaria of Onchocerca volvulus in the dermis. The discovery of an unusual disease in a nonendemic area is an example of the increased complexity of differential diagnosis resulting from the ease of travel from one geographic region to another.

Adolescent↗

Effect of hearing aids on hearing.

We examined 114 patients aged 10 to 91 years with different kinds of hearing aids fitted in one ear only, the unaided ear acting as a control. They were re-examined several times during a period of follow-up from 1 to 9 years comparing the relative change in hearing due to hearing aid usage with various degrees of amplification of the aid. We compared the degree of hearing loss in the aided and unaided ear looking for evidence of a possible change in hearing related to the frequency of hearing aid usage in hours per day and in years, the maximum power output (MPO) and the gain of the aid. According to our findings there is no change in hearing between the aided and the unaided ear at the alpha = 0.05 probability level at least for 8 years. There is no effect of the long-term amplification of the hearing aid on deterioration of hearing comparing the aided ear and the unaided ear, but with high MPO of the aid, the patient should be followed up more frequently than with low MPO amplification.

Adolescent↗

Antibodies spontaneously bound to islet cells in diabetic C57BL/KsJ db/db mice.

Antibodies to pancreatic islet cells were visualized, using an immunohistochemical method with the avidin-biotin-peroxidase complex, either in the islets or sera of diabetic C57BL/KsJ db/db mice. They were revealed within the cytoplasm of all islet cell types. Anti-islet complement-dependent antibodies were demonstrated in vitro in the sera of the same db/db mice. These anomalies were not detected in control littermates. During the life span of db/db mice, cell-bound antibodies were present at early stages, co-existing with hyperinsulinaemia, islet hypertrophy and decreased insulin content of cells. Circulating antibodies were detectable later, before the development of insulinopenia, islet atrophy and cell necrosis. The titre of the immunohistochemical detected complement-fixing antibodies and their lytic potency for islet cells in vitro increased with age. This is the first time that antibodies to islet cells have been revealed within the islets of diabetic animals. Furthermore, anti-islet cell autoantibodies appear very early in db/db islets and may be implicated in the pathogenesis of this murine diabetic syndrome.

Animals↗

Monoclonal anti-islet cell autoantibodies from C57BLKsJ db/db diabetic mice.

We have developed hybridomas producing anti-islet cell monoclonal autoantibodies (IC-MC auto Ab), by fusion of splenocytes from C57BLKsJ db/db diabetic mice with the SP2/O-Ag 14 myeloma. These IC-MC auto Ab were screened by an enzyme-linked immunosorbent assay, for their binding-ability to RINm5F insulinoma cells. Twenty IC-MC auto Ab were produced, which have differing immunoglobulin isotypes. Four of them induced a complement-dependent lysis of RINm5F cells in vitro, while the others did not. These two populations of auto Ab reflect the duality found in the intact db/db mouse. Immunoperoxidase procedures demonstrated that IC-MC auto Ab bound specifically to beta cell antigens of control pancreatic sections, in a similar pattern as auto Ab spontaneously "trapped" in the islets of db/db mice. Electron microscopic studies with an immunogold staining suggested that target antigens for IC-MC auto Ab were predominantly located in the cytoplasmic matrix of beta cells and, to a lesser extent, on their membranes. These antibodies represent powerful reactives for the studies concerning with the pathogeny of diabetes.

Animals↗

Immunoscintigraphy of colon carcinoma.

Two I-131 labeled monoclonal antibodies that react specifically with human gastrointestinal cancers in cell cultures were administered to 90 cancer patients for the scintigraphic detection of cancer sites. Antibody 17-1A, or its F(ab')2 fragments, accumulated significantly in 27 of 46 (59%) colorectal cancer sites, but not in 21 nonepitheliomatous colon cancers and cancers at other sites. Antibody 19-9, or its F(ab')2 fragments, showed significant accumulation in 19 out of 29 (66%) colorectal cancer sites. In 17 patients, immunoscintigraphy with antibody 19-9 correlated with an immunoperoxidase study with the same antibody on resected tissue specimens. In 12 patients injected with two antibodies (17-1A + 19-9, or anti-CEA + 19-9), ten of 13 colorectal cancer sites were positive.

Adult↗

Radioimmunoassay of the CA 12 5 antigen in ovarian carcinomas: advantages compared with CA 19-9 and CEA.

Antigen CA 12 5, associated with ovarian carcinomas, was assayed in the serum by an immunoradiometric method using monoclonal antibody OC 125. In a control group of 67 women in apparent good health, CA 12 5 serum levels in 64 cases (96%) were lower than 35 U/ml, the value arbitrarily considered as the upper normal limit. Using this limit, in benign lesions excluding cirrhosis, 19% (5/27) had raised levels. None of 10 cases with benign ovarian lesions had elevated values. However, in cirrhosis 86% of cases were positive being very high in 43% of cases (greater than 500 U/ml). In 38 cases of ovarian carcinomas, the overall positivity was 92% (35/38); in serous carcinomas it was 96% (26/27). For other non-ovarian cancers, particularly colonic and mammary adenocarcinomas at advanced stages, the positive rate was 43% (19/44). Finally, for 20 patients treated by chemotherapy for ovarian carcinomas and followed up by repeated CA 12 5 assays over a 2 to 8 month period, an increase or decrease in CA 12 5 levels correlated with progression or regression of the disease in 18 cases (90%).

Antibodies, Monoclonal↗

[Effects of the administration of somatostatin 14 in the carcinoid syndrome. Clinical and biological study of 2 cases].

The effects of synthetic cyclic somatostatin 14 were studied in two patients with the carcinoid syndrome. The 3-hour intravenous administration of somatostatin (250 micrograms X h-1), a) resulted in the disappearance of flushing in the first patient but was without any clinical effect in the second subject who remained chronically colored; b) lowered plasma levels of motilin, prostaglandins (E1, E2 and F2 alpha) and to a lesser extent of catecholamines in both patients whereas the serotonin level was not altered; c) was followed by a rebound effect with recurrence of severe flushing in the first patient and was associated with a dramatic increase of prostaglandin, substance P and catecholamine levels in both patients. The inhibitory effect of somatostatin and the occurrence of a rebound effect at the end of infusion were confirmed by infusing somatostatin (6 mg per day) during 48 h in the first patients. These results: a) show that somatostatin is an effective drug in carcinoid syndrome with severe flushing; b) confirm that several mediators are affected in carcinoid syndrome. However it could not be excluded that increased circulating levels of prostaglandins, substance P and catecholamines may represent unrelated secondary events; c) suggest that somatostatin primarily inhibits the release rather than the synthesis of tumor products. Owing to the severity of the rebound effect, treatment of the carcinoid syndrome with somatostatin must be undertaken with precaution until specific long-acting analogs are available.

Aged↗

[Use of radio-labelled monoclonal antibodies for the scintigraphic detection of human colorectal cancers].

Two monoclonal antibodies, 17-1A and 19-9, which recognized human gastrointestinal cancers in cell cultures, were labeled with iodine 131 for immunoscintigraphic application. With the intact 131I-17-1A antibody, 21 out of 35 (60%) primary or secondary colorectal cancer sites were visualized, whereas all 21 nonepitheliomatous colic cancer sites or noncolic cancer sites were negative. With F(ab')2 fragments of the 19-9 antibody, 18 out of 27 (67%) colorectal cancer sites were positive. With both radioantibodies, the best contrasted tumor images were late, 4 to 5 days after injection. A study with paired-label technique, associating a specific iodine-131-labeled antibody with a nonspecific iodine-125-labeled immunoglobulin, demonstrated, that tumor uptake was indeed specific for the 17-1A or 19-9 antibody in tumor and normal colon fragments obtained during operations on 4 patients. A preliminary prospective study showed that only immunoscintigraphy was able to confirm and localize a recurrence of rectal cancer in one patient. A larger series will be necessary to validate the clinical benefit of the technique, as compared with the results of other diagnostic techniques, before immunoscintigraphy can be proposed for routine clinical use.

Antibodies, Monoclonal↗

Double-blind controlled trial of immunosuppression in the treatment of multiple sclerosis: final report.

In a double-blind controlled trial 43 patients with relapsing-remitting multiple sclerosis were treated either with anti-lymphocyte globulin, prednisolone, and azathioprine, or with placebo preparations. Treatment began with a combination of the three medicaments but after 1 month was continued for another 14 months with azathioprine (3 mg/kg dialy) only. There was a marginally beneficial effect of immunosuppression on the overall relapse rate and clinical progression. However, there were significant effects on in-vitro lymphocyte function and in the visual evoked potentials in favour of the group receiving suppressive treatment. Placebo-treated patients of the HLA A3 tissue type had significantly more relapses than placebo-treated patients who were not of type HLA A3. Nevertheless, HLA-A3-positive patients treated with immunosuppression had significantly fewer relapses than A3-positive placebo-treated patients.

Adolescent↗

Effect of somatostatin on diarrhea and on small intestinal water and electrolyte transport in a patient with pancreatic cholera.

The effects of somatostatin on diarrhea and on small intestinal flow of water and electrolytes (slow-marker perfusion technique) in a patient with pancreatic cholera are reported. Continuous intravenous infusion of somatostatin (8 micrograms/kg/hr) suppressed the diarrhea, but a rebound was observed after somatostatin. Infusion of somatostatin at the same dosage decreased the ileal fluid flow rate to within control values. This effect was mainly due to a sharp reduction in the rate fluid entered the jejunum, but was also due to a suppression of the abnormal water and electrolyte secretion in the proximal jejunum. Secretion in the rest of the small bowel remained unchanged. Somatostatin did not noticeably alter the high preinfusion plasma level of prostaglandin E1, but decreased the initially high plasma concentration of vasoactive intestinal peptide to normal values. These results suggest that long-acting somatostatin analogs could be of value in the symptomatic treatment of diarrhea in pancreatic cholera.

Adenoma, Islet Cell↗