Inheritance in idiopathic premature ovarian failure: analysis of 71 cases

Premature ovarian failure is defined as cessation of ovarian function under the age of 40 years and affects approximately 1% of women in the general population. The aetiology of this disorder is still unknown in most cases. Although there have been some reports of familial premature ovarian failure, very little is known about the incidence and inheritance pattern of its idiopathic form. The aims of this study were to investigate the incidence and inheritance pattern of familial premature ovarian failure in a homogeneous group of patients with premature idiopathic menopause and to identify possible clinical differences between patients with the familial and the sporadic form of premature ovarian failure. A total of 71 women were recruited into the study. Clinical assessments and genetic counselling showed that 22 (31%) patients had familial premature ovarian failure, this high incidence strongly suggesting that the disorder is a recognizable heritable entity. There was a statistically significant (P < 0.05) difference in the median age of precocious menopause in patients with sporadic and familial premature ovarian failure (31.0 and 37.5 years of age in the two groups, respectively). Pedigree analysis strongly suggests the existence of a familial pattern of premature ovarian failure with a dominant maternal and/or paternal transmission and incomplete penetrance. In the presence of familial history of premature ovarian failure, reproductive counselling is recommended.      

Diagnostic imaging of human neuroblastoma with radiolabeled antibody

In a previous study, the authors showed that iodine-131 labeled monoclonal antibody (Mab 3F8) could be used to image human neuroblastoma xenografts in mice with excellent tumor-to-tissue ratios. In this study they report their experience with six patients scanned with radiolabeled 3F8. There was strong accumulation of the labeled antibody in viable tumor, but no significant uptake was noted in normal brain, liver, spleen, or adrenal glands. Tumor-to-nontumor activity ratios varied but were approximately 10:1-20:1. This ratio yields good contrast for visualization. Time-activity curves show that radioactivity levels in normal tissue have a half-time of about 40 hours, whereas tumor tissues show a half-time of about 60 hours. Significant gastric secretion of free iodine demonstrated that the Mab was being deiodinated. Calculated radiation doses indicate that tumors receive at least ten times the dose to other tissues. The results indicate that Mab 3F8 has clinical potential for both imaging and therapy of human neuroblastomas.     

Differential responses of granulosa cells from small and large follicles to follicle stimulating hormone (FSH) during the menstrual cycle and acyclicity: effects of tumour necrosis factor-alpha

This study determined effects of follicle stimulating hormone (FSH) alone and in combination with tumour necrosis factor (TNF), on granulosa cells from small (5-10 mm diameter) and large (>10-25 mm) follicles during follicular and luteal phases of the cycle and during periods of acyclicity. Granulosa cells were collected from ovaries of premenopausal women undergoing oophorectomy. The cells were cultured with human FSH (2 ng/ml) and testosterone (1 microM) in the presence or absence of human TNF-alpha (20 ng/ml). Media were removed at 48 and 96 h after culture and progesterone, oestradiol and cAMP in media were measured by radioimmunoassays. FSH stimulated the accumulation of oestradiol from granulosa cells of small follicles during the follicular and luteal phases but not during acyclicity; and TNF reduced oestradiol accumulation in the presence of FSH. Interestingly, in granulosa cells from small follicles, progesterone and cAMP secretion increased in response to FSH and neither was affected by TNF. Thus, TNF specifically inhibited the conversion of testosterone to oestradiol in granulosa cells from small follicles. FSH stimulated oestradiol production by granulosa cells of large follicles obtained only during the follicular phase of the cycle and TNF inhibited the FSH-induced oestradiol secretion. Granulosa cells obtained from large follicles during the luteal phase and during acyclicity did not accumulate oestradiol in response to FSH. However, FSH increased progesterone and cAMP secretion by granulosa cells obtained from large follicles during the follicular and luteal phases. During the luteal phase alone, TNF in combination with FSH increased progesterone accumulation above that of FSH alone. FSH did not increase progesterone, oestradiol or cAMP secretion by granulosa cells obtained from large follicles during acyclicity. Thus, FSH increases progesterone, oestradiol and cAMP secretion by granulosa cells of small follicles during the follicular and luteal phases and TNF appears to inhibit FSH-induced oestradiol secretion specifically in those cells. In large follicles, FSH- stimulated granulosa cell secretion of oestradiol is limited to the follicular phase and this effect can be inhibited by TNF. In addition, when granulosa cells of large follicles do not increase oestradiol secretion in response to FSH, TNF stimulates progesterone secretion.      

Glutamine-enriched enteral nutrition in very low birth weight infants. Design of a double-blind randomised controlled trial [ISRCTN73254583]

Background

Enteral feeding of very low birth weight (VLBW) infants is a challenge, since metabolic demands are high and administration of enteral nutrition is limited by immaturity of the gastrointestinal tract. The amino acid glutamine plays an important role in maintaining functional integrity of the gut. In addition, glutamine is utilised at a high rate by cells of the immune system. In critically ill patients, glutamine is considered a conditionally essential amino acid. VLBW infants may be especially susceptible to glutamine depletion as nutritional supply of glutamine is limited in the first weeks after birth. Glutamine depletion has negative effects on functional integrity of the gut and leads to immunosuppression. This double-blind randomised controlled trial is designed to investigate the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity and short-term outcome in VLBW infants. Furthermore, an attempt is made to elucidate the role of glutamine in postnatal adaptation of the gut and modulation of the immune response.

Methods

VLBW infants (gestational age <32 weeks and/or birth weight <1500 g) are randomly allocated to receive enteral glutamine supplementation (0.3 g/kg/day) or isonitrogenous placebo supplementation between day 3 and 30 of life. Primary outcome is time to full enteral feeding (defined as a feeding volume ≥ 120 mL/kg/day). Furthermore, incidence of serious infections and short-term outcome are evaluated. The effect of glutamine on postnatal adaptation of the gut is investigated by measuring intestinal permeability and determining faecal microflora. The role of glutamine in modulation of the immune response is investigated by determining plasma Th1/Th2 cytokine concentrations following in vitro whole blood stimulation.

     

Postbiopsy bleeding in a porcine model: reduction with radio-frequency ablation--preliminary results

PURPOSE: To test a biopsy needle modified for use of radio-frequency (RF) energy to produce hemostasis after core biopsy of liver or kidney. MATERIALS AND METHODS: RF energy was applied to a partially insulated 17-gauge needle, and tip temperature was monitored with a thermocouple. Domestic Yorkshire pigs (n = 4; mean weight, 23.4 kg) were anesthetized, and their livers and kidneys were exposed. Needles were inserted 2 cm into hepatic and renal parenchyma and retracted, either with or without tract ablation to 65 degrees C, in normal tissue, animals treated with anticoagulants, and an animal with acute inferior vena caval occlusion to produce portal hypertension. Blood loss was assessed by weighing surgical sponges with blood from the puncture sites. Significant differences in blood loss between control and ablated biopsy specimens in each scenario were tested by using a Wilcoxon matched-pairs signed rank test. RESULTS: Mean blood loss for each group was as follows: In the liver, control biopsy specimens (n = 18) lost 0.30 g while ablated biopsy specimens lost 0.00044 g (P <.01), and control biopsy specimens treated with heparin (n = 26) lost 0.45 g while biopsy specimens treated with heparin and ablation lost 0.27 g (P =.03). For inferior vena caval occlusion, control biopsy specimens lost 1.23 g, while ablated biopsy specimens lost 0.00 g. In the kidney, control biopsy specimens (n = 28) lost 0.82 g, while ablated biopsy specimens lost 0.24 g (P =.01), and control biopsy specimens treated with heparin (n = 14) lost 1.04 g, while biopsy specimens treated with heparin and ablation lost 0.19 g (P =.02). CONCLUSION: Tract ablation with thermocouple-monitored RF energy decreased postprocedural hemorrhage after hepatic and renal biopsy.