Fetal death in mice lacking 5alpha-reductase type 1 caused by estrogen excess

Female mice deficient in steroid 5alpha-reductase type 1 have a decreased litter size. The average litter in homozygous deficient females is 2.7 pups vs. 8.0 pups in wild type controls. Oogenesis, fertilization, implantation, and placental morphology appear normal in the mutant animals. Fetal loss occurs between gestation days 10.75 and 11.0 commensurate with a midpregnancy surge in placental androgen production and an induction of 5alpha-reductase type 1 expression in the decidua of wild type mice. Plasma levels of androstenedione and testosterone are 2- to 3-fold higher on gestation day 9, and estradiol levels are chronically elevated by 2- to 3-fold throughout early and midgestation in the knockout mice. Administration of an estrogen receptor antagonist or inhibitors of aromatase reverse the high rate of fetal death in the mutant mice, and estradiol treatment of wild type pregnant mice causes fetal wastage. The results suggest that in the deficient mice, a failure to 5alpha-reduce androgens leads to their conversion to estrogens, which in turn causes fetal death in midgestation. These findings indicate that the 5alpha-reduction of androgens in female animals plays a crucial role in guarding against estrogen toxicity during pregnancy.     

Psychotherapy for gay male couples

Although there is no specific therapy for gay male couples, this paper outlines the more critical issues therapists must understand to provide optimal treatment for gay male dyads. Additionally, the authors present new assumptions arising from their five year research study of 156 gay male couples living together from one to over 37 years. The most therapeutically useful finding is that stages of these relationships parallel stages of clinical development. Each stage has its own unique characteristics, stresses and benefits. Stages are affected by many influences, and individuals can be at different stages simultaneously.     

Choledochoduodenostomy, choledochojejunostomy or sphincteroplasty for biliary and pancreatic disease

Choledochoduodenostomy, choledochojejunostomy, or sphincteroplasty are used in the treatment of selected patients with retained, recurrent, and impacted bile duct stones; strictures of the bile ducts; stenosis of the sphincter of Oddi; pancreatitis associated with biliary disease; choledochal cysts; fistulas of the bile duct; and biliary obstruction, either benign or malignant. From a group of approximately 1600 patients operated on for biliary and pancreatic disease during the 17-year period, 1962 to 1979, 153 patients who had choledochoduodenostomy, choledochojejunostomy or sphincteroplasty were identified. Follow-up information was available for 146 patients (95%). Overall, 84% of the patients had good results, 10% had fair results, and 3% had poor results. A 3% postoperative mortality rate was found, all in patients with unresectable malignancies. Treatment of bile duct obstruction, benign or malignant, was equally effective by choledochoduodenostomy or choledochojejunostomy. Jaundice resolved in all patients; three patients with benign strictures required reoperations for recurrent stricture formation, two after choledochoduodenostomy, and one after choledochojejunostomy. Recurrent cholangitis heralded the development of another stricture. Both choledochoduodenostomy and sphincteroplasty were used for patients with retained, recurrent or impacted duct stones. Pancreatitis did not occur in any patient after sphincteroplasty; the sump syndrome was not seen after choledochoduodenostomy. This review supports the view that choledochoduodenostomy is a safe and effective procedure. All three operative procedures were effective for the problems for which they were used; each procedure has a place in the treatment of recurrent or complicated biliary and pancreatic diseases. The procedures are complementary, not competitive. For certain problems, the operation performed depends upon the surgeon's preference and experience. The indications for and results of these operative procedures are discussed.     

The influence of skeletal muscle incubation medium on fatigue of neuromuscular preparation and on transmitter release at neuromuscular junctions in the frog

The effect of frog skeletal muscle incubate on fatigue was studied in frog sciatic nerve, sartorius muscle preparation. Fatigue was produced by prolonged repetitive (1 s-1) stimulation of motor nerve or of curarized muscle. The incubate partially restored isometric contraction amplitudes of muscle fatigued by nerve stimulation. This effect of partial recovery from fatigue (PRF effect) was exerted mainly by a relatively low-molecular fraction (LMF; < 10 kDa) of the incubate. The incubate and its fractions failed to produce the PRF effect in experiments with directly stimulated muscle. The action of LMF on synaptic transmission in unfatigued cutaneous-pectoris muscle was examined using binomial analysis of quantal transmitter release. LMF produced an increase in the end-plate potential quantal content (m) at synapses with low initial m values. In contrast, it produced a decrease i n m at synapses with higher m values. Both effects were due to respective changes in binomial parameter n. It is assumed that the stimulatory presynaptic action of the incubate on synapses the effectiveness of which was lowered during fatigue, could account for the PRF effect. A possible contribution of low- and high-molecular components of the incubate is discussed.     

The contribution of level of cognitive complexity and pubertal timing to behavioral risk in young adolescents

PURPOSE: To determine the unique contributions of cognitive complexity and pubertal timing to participation in behavioral risk (substance use, sexual activity, school and legal problems) among young adolescents. DESIGN: Cross-sectional with cohort replication. METHODS: Two cohorts of middle school students in grades eight and nine in a midwestern school district completed a self-report questionnaire in 1987 and 1989. Measures of behavioral and emotional risk, cognitive complexity and pubertal timing relative to peers were included. RESULTS: Complete data were available for 817 and 796 students in each cohort year. Gender, race, level of cognitive complexity and pubertal timing each contributed significantly to the variance in behavioral risk independent of chronological age (P < .0001). Boys, whites, those at lower levels of cognitive complexity and those who began pubertal maturation earlier than peers, were at significantly greater risk. Adolescents who demonstrated higher levels of cognitive complexity and those who began puberty later compared to peers participated in a smaller array of risk behaviors, independent of chronological age. IMPLICATIONS: Pediatricians should consider adolescents at lower levels of cognitive complexity (concrete thinking) and those who begin puberty earlier at greater risk for participation in health risk behaviors. Preventive health counseling tailored to the needs of this group may be most beneficial.     

The energy cost of walking before and after significant weight loss

The purpose of this study was to determine whether significant weight loss reduced the energy cost of activity more than that expected based on decreased body weight. Standing energy expenditure was measured and subtracted from the total energy cost of walking to determine ambulatory energy expenditure (AEE). The energy cost of walking was determined in 11 obese women at baseline, week 9 [after 8 wk of a 1758-3349 kJ.d-1 diet], and week 22 (after 2 wk of weight stability). AEE accounted for 80% of the energy cost of walking. Body weight was the principal determinant of AEE, but the relationship was not 1:1. Subjects reduced body weight by 13% at week 9 and 21% at week 22. Analyses which controlled for the relationship between AEE and weight at baseline, showed no change in AEE at week 9. By contrast, at week 22, AEE was reduced more than expected based on a lower body weight. These findings suggest that after significant weight loss, reduced-obese persons will expend less energy for the same activity, even after accounting for the decrease in body weight. These data also suggest that weight-based estimates of exercise energy expenditure may be inappropriate after significant weight loss.     

Analysis of insulin-like growth factors (IGF)-I, and -II, type II IGF receptor and IGF-binding protein-2 mRNA and peptide levels in normal and nephrectomized rat kidney

Immunocytochemistry, in situ hybridization, and radioimmunoassay were employed to examine the cellular distribution of mRNAs and proteins for IGF-I, II, IGF-II/M6P receptor, IGFBP2 as well as the levels of IGF-I and II in normal and unilaterally nephrectomized (Nx) adult rat kidneys. A similar distribution of immunoreactive IGF-I, and -II as well as IGF-II/M6P receptor was found in the principal cells of the cortical collecting duct and in all cells of the inner medullary collecting duct. In addition, immunostainable IGF-I and IGF-II/M6P receptor were noted in some inner medullary loops of Henle, while IGFBP2 was seen in the collecting ducts and loops of Henle of the inner medullar and the renal vasculature of all animals. By comparison, in situ hybridization revealed IGF-I mRNA only in the medullary thick ascending limbs while IGF-II mRNA was localized to the wall of the renal microvasculature in all kidneys. IGFBP2 mRNA was localized to the renal corpuscle and to inner medullary interstitial cells of all kidneys. These data suggest that renal IGF-I and IGFBP2 are synthesized at upstream sites along the nephron and then transported downstream for interaction with IGF receptors. Following nephrectomy, the renal levels of IGF-I peptide and mRNA were elevated at both 5 and 33 days post-nephrectomy, supporting a potential functional role for IGF-I in stimulating the structural and functional recovery in compensatory hypertrophy.