The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction.

To investigate further brain-pituitary-gonadal interrelationships we have generated mice in which the gene encoding the FSH receptor has been disrupted. Female FSH receptor knockout (FSHRKO) mice were infertile. The ovaries were significantly reduced in size, with follicular development arrested at the preantral stage, but there was evidence of stromal hypertrophy. The vagina was imperforate, and the uterus was atrophic. There was no response to administration of PMSG. Inhibins A and B were undetectable in both the serum and gonads. Compared with those in control animals, serum concentrations of FSH and LH were significantly elevated in mutant females. The pituitary content of FSH, but not LH, was also significantly elevated. Estrogen administration in FSHRKO female mice suppressed serum LH levels to those seen in control mice, whereas FSH levels were reduced by only 50%. Male FSHRKO mice were fertile, although testis weight was significantly reduced. However, testicular inhibin A and B concentrations did not differ from those in normal littermates. Serum levels of FSH and LH were elevated in the null mutant male mice, whereas no differences were found in the pituitary content of these hormones. In conclusion, ovarian follicular development cannot progress beyond the preantral stage without FSH. In the absence of mature follicles ovarian estrogen remains low, and consequently accessory sex tissue growth and negative feedback regulation of gonadotropin secretion are severely compromised. In the male, however, inability to respond to FSH does not impair fertility, although testicular weight is reduced, and feedback regulation of pituitary gonadotropins and intratesticular paracrine interactions may be disturbed.

Cross-clade envelope glycoprotein 160-specific CD8+ cytotoxic T lymphocyte responses in early HIV type 1 clade B infection.

A major objective of current HIV-1 vaccination strategies is the induction of HIV-1-specific CD8+ MHC class I-restricted CTL responses, which are suggested to play a pivotal role in viral clearance and protection against HIV-1 disease progression. However, the marked genetic diversity of HIV-1 and existence of distinct viral subtypes or clades could potentially hinder the development of a universally efficacious HIV-1 vaccine. In this study we examined HIV-1 intraclade (B(LAI) versus B(MN)) Env gp160-specific CTL reactivity in recently HIV-1 clade B-infected individuals. We further evaluated the extent of interclade CTL cross-recognition of the divergent A and C Env gp160 subtypes, that are highly prevalent in the global pandemic. Freshly isolated PBMCs were stimulated in vitro with autologous PBMCs infected with recombinant vaccinia vectors expressing HIV-1 env, gag, pol, and nef genes derived from HIV-1 clade B. All 13 of the 19 HIV-1-seropositive subjects who elicited significant clade B Env gp160LAI CD8+ CTL responses also demonstrated comparable levels of CTL cross-reactivity against clade C92BR025 Env gp160. Nine of these individuals also showed extensive interclade CTL cross-recognition of clade A92UG037 Env gp160. Two HLA class I B7 donors had nondetectable intraclade CTL response against B Env gp160MN, while generating significant intraclade B(LAI) and interclade (A and C) Env gp160 CTL cross-reactivity. These observations serve to underscore the central importance of the HLA background of individuals in determining the pattern of immune reactivity to natural HIV-1 infection and presumably vaccines. Five donors studied also demonstrated broad CTL cross-reactivity against clade A92UG037 Gag p55, Pol, and/or Nef antigens. In conclusion, this present study indicates that there is a considerable degree of CD8+ CTL cross-recognition of the highly divergent HIV-1 Env gp160 subtypes during early phases of HIV-1 infection. Such findings suggest that HIV-1 vaccines based on a single clade that can induce extensive cross-clade immunity may demonstrate utility in diverse geographical regions.

Contamination of underwater seal drainage systems in thoracic surgery.

The incidence of bacteriological contamination of drainage fluid (water constituting the underwater seal plus drainage effluent) was studied in 38 patients (50 chest drains), up to 6 days after thoracotomy. No bacteriological contamination was demonstrated in any of the samples taken during this period of time. We conclude that the underwater seal drainage system may be left for up to 6 days postoperatively without change of any of its components and without risk of contamination.

Pediatric hotline. Meeting community needs while conserving healthcare dollars.

Faced with the challenge of providing cost effective services, administrators at the Hospital for Sick Children in Toronto, Canada recognized an opportunity to reduce unnecessary emergency visits. A telephone hotline was established to provide parents with reassurance and treatment guidelines that allowed them to care for their children at home.

How effective is syndromic management of STDs?: A review of current studies.

BACKGROUND: Studies of the accuracy of syndromic management have demonstrated widely varying results depending upon gender, location of infection, risk group, organisms, among other factors. GOAL: To review current knowledge about syndromic management of sexually transmitted diseases (STDs) and to make recommendations about the strengths and weaknesses of different syndromic management algorithms. STUDY DESIGN: The authors identified articles and abstracts about the syndromic management of STDs. Evaluation of the effectiveness of algorithms for urethral discharge, genital ulcer disease, and vaginal discharge was based primarily on published sensitivity and specificity data. RESULTS: Overall, algorithms for the diagnosis and treatment of urethral discharge and genital ulcer disease in men had high sensitivities or cure rates (urethral discharge, 87-99%; genital ulcer disease, 68-98%). The sensitivities for the algorithms for vaginal discharge ranged from 73% to 93% among women presenting with symptoms of vaginal discharge, and from 29% to 86% among women not presenting with symptoms. Vaginal discharge was not found to be an effective indicator of cervical infection and, therefore, is not an independently effective screening tool to detect women with cervical infection, especially in low-risk or asymptomatic populations. Incorporating risk scores can improve the accuracy of algorithms to detect cervical infection. CONCLUSIONS: Algorithms for urethral discharge and genital ulcer disease can be effective in STDs. The current algorithms for vaginal discharge are not highly effective in detecting gonorrhea and chlamydia in women; risk scores can improve their efficacy, but must be tailored to reflect community risks. Without attention to the qualitative aspects of STD syndromic management, these methods will likely have even less accuracy than the studies reviewed above. There remains an urgent need for the development of an affordable, rapid, and effective diagnostic technique that will improve STD detection in resource-poor settings.