Haemodynamic Effects of Low Doses of Female Sex Steroids

Summary: Haemodynamic changes were monitored serially in 3 groups of healthy young women taking (i) a combined oestrogen-gestagen oral contraceptive containing a low dose of oestrogen, (ii) an oestrogen alone and (iii) a gestagen alone. Similar significant increases in plasma volume occurred in those women taking the combined preparation and in those taking the oestrogen. A small but significant decrease in forearm blood flow occurred in subjects taking the combined oral contraceptive. Cardiac output, blood pressure, heart rate and hand blood flow did not alter significantly in any of the 3 groups of subjects, while body weight increased in the subjects taking gestagen alone.
It is concluded that the combined oestrogen-gestagen oral contraceptives containing 50 μg. of oestrogen result in minimal haemodynamic side effects, and hence are safer than the older combined preparations containing a higher dose of oestrogen. The increase in plasma volume observed was due to oestrogen rather than gestagen. No additional information was obtained concerning the site of sex steroid action in the cardio-vascular system.     

Interleukin-2 Induced Systemic Toxicity: Induction of Mediators and Immunopharmacologic Intervention

Interleukin-2 has been tested as an anti-cancer agent, either alone or in combination with immune cells, but severe dose limiting adverse toxic effects have been observed. Because the pathogenesis c the toxicity has remained uncharacterized, it has not been possible to determine whether the therapeutic and the toxic events could be separated. We have examined immunopharmacologic regulation of IL2 induced mediator induction and toxicity syndrome and have compared this data with our earlier information on IL2 enhancement of immune function in murine systems. The results of this study have shown that treatment with recombinant human interleukin-2 induced increased cellular TNF activity in lymphoid organs and this activity was abrogated by an anti-TNF antibody. Additionally, continuous daily treatment with interleukin-2 also induced increases in serum corticosterone but no detectable increases in serum IL1 or TNF. The increases in serum corticosterone occured later in the treatment process and coincided with histopathologic changes in the adrenal glands and other tissues. Animals that died as a result of IL2 treatment had ascites and hydrothorax. Histopathologic changes were noted in the lungs, liver, adrenals, kidneys, gastrointestinal tract, heart and lymphoid organs. Cyclophosphamide, dexamethasone and anti-ASGM1 antibody were most effective in increasing survival and inhibiting immune enhancement but differentially effective in inhibiting TNF induction (or in certain cases gamma interferon induction), decreasing ascites or hydrothorax or affecting lymphoid proliferation in the lungs and spleen. Cyclosporin A and azathioprine were not as effective in enhancing survival and had differential effects on the other parameters. Possible mechanisms of both therapeutic and toxic events are discussed.     

Stimulus intensity modulation and alcohol consumption

In a study of men alcoholics, cortical average evoked response proved to be a good indicator of subsequent alcohol acquisition and consumption behavior in the laboratory.     

Mitrofanoff channel survival after pedicle ligation

In patients who have undergone complex genitourinary reconstruction, additional abdominal surgery is often required. We report 2 cases in which the blood supply to an existing Mitrofanoff channel was divided. In both cases, the conduits appeared to remain well perfused, presumably based on collateral blood supply. Both conduits remained healthy and functioning at more than 1 year of follow-up.     

Autotransplantation of pancreatic islets without separation of exocrine and endocrine tissue in totally pancreatectomized dogs.

The aims of this study were to determine whether diabetes could be ameliorated in dogs by autotransplantation of pancreatic fragments to the spleen and to determine the optimal time of collagenase digestion for pancreatic tissue dispersal. Forty-eight dogs were made diabetic by total pancreatectomy. Fifteen dogs not further treated survived 7.0+/-1.1 (SE) days with a mean plasma glucose of 401+/-5 (SE) mg/100 ml 2 days after pancreatectomy. The pancreases of 33 dogs were distended with Hanks' solution, minced, digested with collagenase (600 microns/ml of tissue), for 0 to 25 minutes, and autotransplanted to the splenic pulp. The incidence of permanent normoglycemia (fasting plasma glucose less than 150 mg/100 ml) and the K value of glucose tolerance tests (GTT) performed 2 and 10 weeks after transplant were determined in experimental groups divided according to the length of collagenase digestion. All five dogs receiving undigested tissue remained hyperglycemic. One of seven dogs receiving tissue digested for 10 minutes became normoglycemic. In contrast, seven of eight, seven of seven, and six of six dogs receiving tissue digested for 15, 20, and 25 minutes, respectively, became normoglycemic (followed for 6 months). K values at 2 weeks were 1.20+/-1.19 (SE)% 1.60+/-0.25 (SE)%, and 0.78+/-0.08 (SE)% in the normolgycemic dogs of the 15, 20, and 25 minute digestion groups, respectively. The K value of normal dogs was 3.30+/-0.27 (SE)%. The glucose tolerance curves of the 20 minute group at 2 and 10 weeks most nearly approximated the curves of normal dogs. K values improved in all recipient dogs. Diabetes recurred immediately and death occurred at a mean of 4.8+/-1.5 days in 12 recipient dogs following splenectomy. We conclude that pancreatic fragments can be successfully autotransplanted to the spleen without separation of endocrine and exocrine tissue and that 20 minutes is the optimal period of collagenase digestion for tissue preparation.