Protective effect of an oestrogen against endotoxin-induced liver enzyme release.

Groups of mice were given oestrone acetate or vitamin E subcutaneously to determine how these treatments might modify responses to endotoxic lipopolysaccharide given intraperitoneally. Release of hepatic transaminase and tumour necrosis factor (TNF) into serum and induction of manganous superoxide dismutase in the liver were measured. Significantly less transaminase and TNF were released into the circulation in mice given the steroid or vitamin E before the endotoxin. In endotoxin-treated animals oestrogen administration did not influence induction of the superoxide dismutase. It is postulated that protection of the liver in these experiments arises from a direct pharmacological antioxidant effect of the oestrogen.

Imipenem-cilastatin in the treatment of respiratory infections in patients with chronic airways obstruction.

Chest infections with organisms resistant to conventional antibiotics are common in patients with chronic lung disease. We have studied the use of imipenem in 40 (28 M 12 F) patients admitted for treatment of chest infections. Patients were treated with imipenem 0.5 g four times daily by intravenous infusion for 6.3 +/- 1.6 (S.D.) days. Forty-six respiratory pathogens were cultured from 36 patients including 18 Haemophilus influenzae, 6 H. parainfluenzae, 6 Streptococcus pneumoniae, 8 Pseudomonas aeruginosa, and 6 Branhamella catarrhalis. Forty-three of the 46 isolates were sensitive to imipenem, 28 to ampicillin, 33 to tetracycline and 35 to cotrimoxazole. Thirty-eight of the 40 patients improved clinically, and 34 of the 36 patients with positive sputum culture had no pathogens in their sputum after treatment. Twenty patients developed minor phlebitis at the infusion site but there were few other side effects. Imipenem may prove useful in the treatment of chest infections, particularly when the organism is resistant to conventional antibiotics.

Amniotic fluid microvillar enzyme activities in the early detection of fetal abnormalities.

Measurement of the microvillar enzymes, gamma-glutamyltranspeptidase (GGTP), aminopeptidase M (APM) and alkaline phosphatase (ALP), in amniotic fluid supernatant has been proposed as a method for the early prenatal diagnosis of cystic fibrosis. The activities of these enzymes in a series of other fetal abnormalities have now been examined. GGTP activities were below the 5th percentile in 28 out of 54 cases of trisomy 21 and 9 of 14 cases of trisomy 18, while APM values were below this cut-off in 26 of 54 cases of trisomy 21 and 8 of 14 cases of trisomy 18. Abnormal ALP isoenzyme ratios were found in 6 of 54 cases of trisomy 21 and 4 of 14 cases of trisomy 18. If prenatal cytogenetic studies are routinely carried out on amniotic fluid cells, the occasional confounding effect of abnormal microvillar enzymes associated with fetal trisomies rather than with cystic fibrosis should be avoided.

Microvillar peptidase activity in amniotic fluid: possible use in the prenatal diagnosis of cystic fibrosis.

The activities of two microvillar peptidases, gamma-glutamyl transpeptidase (GGTP) and aminopeptidase M (APM), have been measured in 132 samples of mid-trimester amniotic fluid. These included samples from 16 pregnancies at risk for cystic fibrosis. The activities of both peptidases were significantly below the normal range in amniotic fluids from the 6 affected pregnancies. This points to early pathological changes in fetal tissues in which microvilli are prominent. In contrast, 4-methylumbelliferylguanidinobenzoate-reactive protease activity in amniotic fluid from the 6 affected pregnancies was normal. Correlation of individual values between GGTP and APM was close in all cases examined, so that when a further 7 samples from cases at risk became available they were tested for GGTP alone. Of these, the 3 affected pregnancies had significantly reduced GGTP activity, particularly in the early weeks of gestation. It is suggested that early amniocentesis and examination of gamma-glutamyl-transpeptidase isoenzyme constitution might make possible the reliable early diagnosis of cystic fibrosis.