Clinical comparison between glucose and sucrose additions to a basic electrolyte mixture in the outpatient management of acute gastroenteritis in children.

In a double-blind trial in 94 children attending outpatients the value of glucose or a sucrose addition to a basic electrolyte mixture for the management of acute gastroenteritis was compared. Of the children treated with added sucrose 10% failed to respond compared with 27% of those treated with added glucose. This difference was significant (P=0-05), but the time to recovery in those in the two groups who responded to treatment was not significantly different. Thus, despite theoretical advantages, there was no practical advantage in using glucose rather than sucrose. A 5% sucrose electrolyte solution with its relatively low osmolality, ready availability, and ease of preparation is recommended as the treatment of choice in the outpatient management of acute gastroenteritis in infancy.     

Quality of life (QOL) assessment of MIP (mitomycin, ifosfamide and cisplatin) chemotherapy in advanced non-small cell lung cancers (NSCLC)

BACKGROUND: Quality of life (QOL) assessment has emerged to measure and quantify the balance between treatment benefit and toxicity, and has a value in predicting response and overall survival in cancer patients. METHODS: From July 1995 to February 1997, 38 symptomatic patients with advanced non-small cell lung cancer (NSCLC) were treated with MIP chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50 mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including physical well-being, general symptoms and lung cancer-specific symptoms, as well as objective response. RESULTS: The overall response rate was 38.9% (14/36, all were partial response) and the median duration of response was 3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using multiple clinical predictors of survival (age, histology, stage, performance status), only change of QOL emerged significantly (P = 0.0007). CONCLUSIONS: MIP had an endurable response and low toxicity profile, and provided good QOL. Integral QOL data in our study provided the strong prediction of survival in advanced NSCLC. Further experienced QOL study will provide greatly enhanced outcome data in clinical trials.      

Steroids modulate corticotropin-releasing hormone production in human fetal membranes and placenta

The levels of immunoreactive CRH are elevated in both maternal and fetal plasma in late gestation and labor, but fall precipitously after parturition. The major source of this peptide is thought to be the placenta. We determined if the placenta and also the amnion, chorion, and decidua produce CRH, whether this material has biological activity, and whether CRH output is modulated by glucocorticoids and progesterone. In an in vitro monolayer culture system CRH was produced by the fetal membranes and decidua. Media immunoreactive CRH concentrations averaged 625 +/- 45 (SE) pg/10(5) cells in amnion, 701 +/- 56 pg/10(5) cells in chorion, and 580 +/- 60 pg/10(5) cells in decidual tissue obtained at cesarean section. This output was similar to that by the placenta (906 +/- 121 pg/10(5) cells). These values increased in tissue obtained after spontaneous labor. A single peak of CRH immunoreactivity eluting at the same position as synthetic human CRH, and possessing biological activity, was found in all tissues. There was a dose-dependent increase in CRH output by all tissue types when cells were maintained in the presence of increasing concentrations of cortisol and dexamethasone. In contrast, increasing concentrations of progesterone decreased CRH output by all tissue types. We conclude that immuno- and biologically active CRH is produced not only in the human placenta, but also in the fetal membranes. CRH output by the placenta/fetal membranes is moderated by steroids, and changes with labor. These findings raise the possibility of a regulatory system similar to that of the hypothalamic pituitary axis, but residing within the placenta and fetal membranes.     

Influence of 20 alpha-dihydroprogesterone on progesterone output by human chorion explants

The output of progesterone by explants of chorion incubated without exogenous precursor was increased in the presence of 20 alpha-dihydroprogesterone (20 alpha-diHP). We have now examined the nature of the 20 alpha-diHP effect. Explants of chorion were incubated with [3H]progesterone and 3 microM non-radiolabelled 20 alpha-diHP to examine the effect of 20 alpha-diHP on progesterone metabolism. Significantly more radioactivity remained as unmetabolized [3H]progesterone compared to chorion incubated in the absence of non-radiolabelled 20 alpha-diHP. There was also a decrease in the output of [3H]-20 alpha-diHP by the explants but no change in the output of a second metabolite of progesterone [3H]-5 alpha-pregnanedione. When explants were incubated with 20 alpha-diHP in the presence of the 3 beta-hydroxysteroid dehydrogenase inhibitor, trilostane, the output of progesterone was significantly greater than with explants incubated with trilostane but without addition of 20 alpha-diHP. Radiochemically pure [3H]progesterone was produced by explants of chorion incubated with [3H]-20 alpha-diHP. We conclude that 20 alpha-diHP may serve as substrate for chorionic progesterone production through 20 alpha-hydroxysteroid dehydrogenase. 20 alpha-diHP, formed from progesterone, may also exert product feedback inhibition on this enzyme.     

The effect of prenatal betamethasone administration on postnatal ovine hypothalamic-pituitary-adrenal function.

Prenatal exposure to glucocorticoids is associated with alterations in fetal growth and endocrine function. However, few studies have examined the effects of clinically relevant doses of glucocorticoids on postnatal hypothalamic-pituitary-adrenal (HPA) function. To determine the effects of maternal or fetal betamethasone administration (0.5 mg/kg maternal or estimated fetal weight) on postnatal HPA function at 6 months and 1 year postnatal age, pregnant ewes were randomized into the following treatment groups: no treatment (n=6); maternal saline (n=6); single maternal betamethasone (M1) (n=6); repeated maternal betamethasone (M4) (n=6); fetal saline (n=5); single fetal betamethasone (n=6) and repeated fetal betamethasone (F4) (n=6). Single injections were given at 104 days of gestation and repeated injections at 104, 111, 118 and 125 days. Lambs were born spontaneously and the ACTH and cortisol responses to i.v. corticotropin-releasing hormone (CRH) (0.5 microg/kg) plus arginine vasopressin (AVP) (0.1 microg/kg) were measured at 6 months and 1 year postnatally. At 6 months postnatal age, neither maternal nor fetal prenatal betamethasone administration altered significantly the ACTH and cortisol responses to CRH+AVP. However, in animals at 1 year postnatal age, a previous single injection of betamethasone to the mother (M1) resulted in significantly elevated basal and stimulated cortisol levels (P<0.05), without significant change in the ACTH response. In contrast, betamethasone administration to the fetus resulted in significantly attenuated ACTH responses to CRH+AVP at 1 year compared with control animals (P<0.05), but these were not associated with any significant changes in basal or stimulated cortisol levels. All control animals exhibited a significant increase in peak ACTH responses to CRH+AVP between 6 months and 1 year postnatal age (P<0.05). After prenatal betamethasone (F4, M4) the difference in peak ACTH response between animals at 6 months and 1 year postnatal age was abolished. We conclude that in sheep between 6 months and 1 year postnatal age, HPA function undergoes developmental changes that are influenced by prenatal glucocorticoid exposure. Furthermore, the effects of glucocorticoid on postnatal HPA responses may vary according to the time in gestation that the steroid was administered, and whether it was given directly into the fetal or maternal compartment.