Effect of maternal betamethasone administration at midgestation on baboon fetal adrenal gland development and adrenocorticotropin receptor messenger ribonucleic acid expression

Although fetal pituitary ACTH is important to fetal adrenal growth and steroidogenesis in the second half of primate pregnancy, its role in adrenal development and function has not been established in vivo in the first half of gestation. In the present study, therefore, baboons were treated at midgestation with betamethasone to determine the effect of fetal pituitary ACTH on fetal adrenal growth, development, and ACTH receptor and P-450 enzyme messenger ribonucleic acid (mRNA) levels. The administration of betamethasone to baboon mothers on days 60-99 of gestation (term = 184 days) decreased fetal pituitary POMC mRNA levels by 54% (P < 0.01) and fetal serum ACTH levels to undetectable values (P < 0.05). The decline in ACTH was associated with decreases in fetal adrenal weight (P < 0.001), cortical cell size (P < 0.05), appearance of apoptosis and cellular disorganization, and a loss of immunocytochemically demonstrable definitive zone-specific delta5-3beta-hydroxysteroid dehydrogenase expression. The concomitant administration of ACTH and betamethasone restored these aspects of adrenal integrity to normal. Moreover, there was approximately a 95% decrease (P < 0.01) in fetal adrenal expression of ACTH receptor, P-450 cholesterol side-chain cleavage, and P-450 17alpha-hydroxylase 17/20-lyase mRNA levels after betamethasone administration. We conclude that fetal pituitary ACTH is necessary for the growth and development of fetal and definitive cortical zones and the marked coordinated increase in ACTH receptor and maintenance of P-450 cholesterol side-chain cleavage/P-450 17alpha-hydroxylase 17/20-lyase expression in the baboon fetal adrenal gland during the first half of gestation.     

Age differences in behaviors leading to completed suicide

Nonclostridial necrotizing soft-tissue infections are usually polymicrobial, with greater than 90 per cent involving beta-hemolytic streptococci or coagulase-positive staphylococci. The remaining 10 per cent are usually due to Gram-negative enteric pathogens. We describe the case of a 46-year-old woman with bilateral lower extremity fungal soft tissue infections. She underwent multiple surgical debridements of extensive gangrenous necrosis of the skin and subcutaneous fat associated with severe acute arteritis. Histopathological examination revealed Aspergillus niger as the sole initial pathogen. Despite aggressive surgical debridement, allografts, and intravenous amphotericin B, her condition clinically deteriorated and she ultimately died of overwhelming infection. Treatment for soft-tissue infections include surgical debridement and intravenous antibiotics. More specifically, Aspergillus can be treated with intravenous amphotericin B, 5-fluorocytosine, and rifampin. Despite these treatment modalities, necrotizing fascitis is associated with a 60 per cent mortality rate. Primary fungal pathogens should be included in the differential diagnosis of soft-tissue infections.     

Kinetic analysis of dynamic 13C NMR spectra: metabolic flux, regulation, and compartmentation in hearts

Control of oxidative metabolism was studied using 13C NMR spectroscopy to detect rate-limiting steps in 13C labeling of glutamate. 13C NMR spectra were acquired every 1 or 2 min from isolated rabbit hearts perfused with either 2.5 mM [2-13C]acetate or 2.5 mM [2-13C]butyrate with or without KCl arrest. Tricarboxylic acid cycle flux (VTCA) and the exchange rate between alpha-ketoglutarate and glutamate (F1) were determined by least-square fitting of a kinetic model to NMR data. Rates were compared to measured kinetics of the cardiac glutamate-oxaloacetate transaminase (GOT). Despite similar oxygen use, hearts oxidizing butyrate instead of acetate showed delayed incorporation of 13C label into glutamate and lower VTCA, because of the influence of beta-oxidation: butyrate = 7.1 +/- 0.2 mumol/min/g dry wt; acetate = 10.1 +/- 0.2; butyrate + KCl = 1.8 +/- 0.1; acetate + KCl = 3.1 +/- 0.1 (mean +/- SD). F1 ranged from a low of 4.4 +/- 1.0 mumol/min/g (butyrate + KCl) to 9.3 +/- 0.6 (acetate), at least 20-fold slower than GOT flux, and proved to be rate limiting for isotope turnover in the glutamate pool. Therefore, dynamic 13C NMR observations were sensitive not only to TCA cycle flux but also to the interconversion between TCA cycle intermediates and glutamate.     

Further characterization of the DFNA1 audiovestibular phenotype

BACKGROUND: Autosomal dominant, nonsyndromic, hereditary hearing impairment in a large Costa Rican kindred is caused by a mutation in the human homolog of the Drosophila diaphanous gene. OBJECTIVE: To further characterize the phenotype of DFNA1 with comprehensive audiovestibular evaluation and computed tomography of the temporal bone. PATIENTS: One affected child and 2 affected adults of the Costa Rican kindred who harbor a mutation in the diaphanous gene. SETTING: Medical Center at the University of California, San Francisco. INTERVENTION: Otologic and neuro-otologic examination; pure tone audiometry, speech audiometry, and immitance testing; auditory evoked potentials, electrocochleography, and otoacoustic emissions; electronystagmography and vestibular autorotation tests; and computed tomography of the temporal bone. RESULTS: The youngest subject, an 8-year-old boy, had a mild hearing loss, intact stapedial reflexes, otoacoustic emissions at high frequencies, normal auditory evoked potentials, and electrocochleographic findings consistent with endolymphatic hydrops. The two adults had severe to profound bilateral sensorineural hearing impairment. Electronystagmography disclosed normal vestibular function. Computed tomography demonstrated normal external, middle, and inner ear structures. CONCLUSIONS: These results suggest that the early low-frequency hearing loss in this family is associated with endolymphatic hydrops. Elucidation of the role of the diaphanous gene in hearing will therefore lead to a better understanding of the mechanism of endolymphatic hydrops.     

Timolol gel versus acetazolamide in the prophylaxis of ocular hypertension after phacoemulsification

PURPOSE: To compare postoperative intraocular pressure (IOP) after administration of acetazolamide and timolol following phacoemulsification and intraocular lens implantation. SETTING: Ophthalmic Consultants of Long Island, Rockville Centre, New York, USA. METHODS: Sixty patients were included in a prospective, randomized, masked trial. The patients received either two doses of oral, sustained-release acetazolamide (Diamox Sequels) or a single dose of topical timolol 0.5% gel (Timoptic XE). Intraocular pressure was measured by Goldmann applanation tonometry preoperatively and 1 day postoperatively. RESULTS: Mean preoperative IOP was 16.4 mm Hg. One day postoperatively, it was 19.5 mm Hg in the oral acetazolamide group and 15.9 mm Hg in the timolol gel group. One patient in the acetazolamide group developed significant adverse reactions. CONCLUSION: Prophylactic use of topical timolol 0.5% gel for viscoelastic-induced ocular hypertension after cataract extraction appears to offer better IOP control than oral acetazolamide and has potentially fewer adverse systemic effects.     

Determinants of children's health care use: an investigation of psychosocial factors

Factors related to the amount of health care used by 5- to 11-year-old children in a health maintenance organization (HMO) were investigated using a comprehensive multivariate model that assessed the contribution of child health need, mental health, and social functioning; maternal mental health, social support and health care utilization; and family functioning and life events. Mothers reported on the 450 participating children. Health care visits for a two-year retrospective period were obtained from the computerized encounter system. Child health need and maternal patterns of health care use were powerful predictors of the overall amount of health care used, and these factors discriminated high users from low users of care. Family conflict was associated with a higher volume of care, while children's depressive symptoms and non-white race were related to lower use. Maternal social support, mental health, and life events were not predictive of use in either full multivariate model. Enabling factors were held relatively constant by participation of all families in a prepaid HMO. The multiple regression model explained 33% of the variance in use, slightly more than in previous studies of children's health care use. When included in a comprehensive analysis, child and family psychosocial characteristics help to explain children's health care use beyond what is possible using simple health and illness variables. The implications of these findings in the development of further research and to the practice of routine pediatric care are discussed.