Amino acid position 11 of HLA-DRß1 is a major determinant of chromosome 6p association with ulcerative colitis.

The major histocompatibility complex (MHC) on chromosome 6p is an established risk locus for ulcerative colitis (UC) and Crohn's disease (CD). We aimed to better define MHC association signals in UC and CD by combining data from dense single-nucleotide polymorphism (SNP) genotyping and from imputation of classical human leukocyte antigen (HLA) types, their constituent SNPs and corresponding amino acids in 562 UC, 611 CD and 1428 control subjects. Univariate and multivariate association analyses were performed, controlling for ancestry. In univariate analyses, absence of the rs9269955 C allele was strongly associated with risk for UC (P = 2.67 × 10(-13)). rs9269955 is a SNP in the codon for amino acid position 11 of HLA-DRß1, located in the P6 pocket of the HLA-DR antigen binding cleft. This amino acid position was also the most significantly UC-associated amino acid in omnibus tests (P = 2.68 × 10(-13)). Multivariate modeling identified rs9269955-C and 13 other variants in best predicting UC vs control status. In contrast, there was only suggestive association evidence between the MHC and CD. Taken together, these data demonstrate that variation at HLA-DRß1, amino acid 11 in the P6 pocket of the HLA-DR complex antigen binding cleft is a major determinant of chromosome 6p association with UC.

Climacteric symptoms in women undergoing risk-reducing bilateral salpingo-oophorectomy.

BACKGROUND: The most effective strategy for prevention of ovarian and breast cancer in high-risk women is bilateral salpingo-oophorectomy. The inevitable consequence of the procedure is early menopause with the associated climacteric symptoms. Little is known about the nature of the symptoms in women who undergo risk-reducing bilateral salpingo-oophorectomy. OBJECTIVES: To compare the nature, frequency, severity, duration, and overall effects of climacteric symptoms in a group of women who underwent preventive bilateral salpingo-oophorectomy as compared to women who experienced natural menopause. METHODS: Forty-eight women at high risk for ovarian cancer who had risk-reducing bilateral salpingo-oophorectomy were compared to 60 postmenopausal women who had natural menopause. The participants were interviewed about their climacteric complaints, thoughts and feelings regarding the surgical procedure and their general well-being. The climacteric symptoms were evaluated by a modified Greene Climacteric Scale. RESULTS: Surgical menopause, as compared to natural menopause, was associated with more severe psychological, vasomotor and somatic climacteric symptoms (total score 17.36 vs. 8.65, respectively, p < 0.001) and more significant sexual dysfunction (1.848 vs. 0.900, respectively, p < 0.01). On a 0-10 scale, the satisfaction rate from the surgical procedure was 8.23 +/- 2.21. The surgery did not affect the perceived quality of life (p = 0.347) and decreased the score of anxiety and cancer fear (from 7.75 +/- 3.31 preoperatively to 2.94 +/- 3.08 postoperatively, p < 0.001). CONCLUSIONS: Risk-reducing bilateral salpingo-oophorectomy as compared to natural menopause is associated with more severe climacteric symptoms. However, the procedure does not interfere with the overall perceived quality of life and improves the perception of cancer risk.

Raloxifene: cardiovascular considerations.

Ovarian hormone deficiency status is associated with increased cardiovascular morbidity and mortality, suggesting that estrogen might exhibit a favorable cardiovascular effect. Estrogen has a multitude of beneficial biological effects on surrogate markers of cardiovascular disease that may account for this hypothesis. However, none of the randomized trials already conducted with hormone replacement therapy showed overall benefit by means of reducing clinical ischemic cardiovascular events and/or suppressing atherogenesis. Moreover, the Women's Health Initiative study (WHI) has suggested a possible detrimental effect for hormone replacement therapy including increased cardiovascular morbidity, ovarian and breast cancer. Hence, any beneficial effect of estrogen must be carefully weighed against its carcinogenic properties together with its side effects. The need for a more efficient and specific molecule led to the development of the selective estrogen receptor modulators (SERMs). This new generation of drugs mimic the effect of estrogen in some tissues while antagonize several estrogen effects in other tissues. These unique properties offer the possibility to attain the beneficial effects of estrogen while avoiding its carcinogenic effect and the accompanying adverse reactions. Here we review the different effects of raloxifene- a protype second generation SERM on the cardiovascular system. We discuss raloxifene's role at different levels of the atherothrombotic cascade addressing each level separately; trying to clarify the net effect of raloxifene in modulating thrombosis in the arterial tree.

(Re)moving the needle: prospects for all-oral treatment for multidrug-resistant tuberculosis.

BACKGROUND: Currently recommended regimens for multidrug-resistant tuberculosis (MDR-TB) contain painful daily injections and are unsuccessful in approximately half of patients. Removal of the injectable agent to fashion all-oral regimens could transform MDR-TB treatment and access to care. OBJECTIVE: To explore evidence for all-oral treatment regimens. DESIGN: We review evidence on drugs that could be included in injection-free MDR-TB regimens. The oral drugs considered have an indication for or are recommended for off-label use for TB or MDR-TB, and have demonstrated bactericidal activity. Drugs with weak bactericidal activity should have limited prior population exposure and evidence of effectiveness in MDR-TB regimens. RESULTS: Bedaquiline, delamanid, and linezolid all display strong bactericidal activity, while clofazimine has weak bactericidal activity. They all have limited prior population exposure and demonstrated effectiveness in MDR-TB regimens. Despite widespread exposure to pyrazinamide and late-generation fluoroquinolones in the population, all are bactericidal and have shown great value when included in treatment regimens for MDR-TB. CONCLUSION: The evidence supports the use of all-oral regimens comprising new and existing drugs for MDR-TB treatment. Existing evidence of bactericidal activity and efficacy for these drugs provides a convincing argument for transitioning MDR-TB treatment towards all-oral regimens. These new regimens could mitigate the delivery, cost, and adherence challenges inherent to the current standard.

Isolation of A-T-rich fragments from calf thymus DNA using the phenol method.

The action of phenol on the products of partial digestion of calf thymus DNA by K2 DNAase causes a loss of 3--5% of the material passing into the phenol phase. This part of DNA can be regained in the aqueous phase by lowering both the temperature and the ionic strength. Among oligonucleotides up to 7 monomers in length, those which are soluble in phenol do not contain guanine residues. Phenol-soluble DNA fragments of the molecular weight of an order of 2000--50,000 appeared to be composed mainly of adenosine phosphate. They also contain some thymine and only traces of guanine and cytosine. Some longer A-T-rich fragments, even up to 5-10(6) daltons, were repeatedly found in the phenol phase, but their base composition has not been determined yet. The method presented here was found very convenient for the isolation of relatively large A-T-rich DNA fragments. The property of DNA or its fragments to dissolve in phenol seems to be dependent on an adequate primary structure, probably similar to that of poly (dA-dT).

Maintenance therapy with a probiotic in antibiotic-dependent pouchitis: experience in clinical practice.

BACKGROUND: Management of antibiotic-dependent pouchitis is often challenging. Oral bacteriotherapy with probiotics (such as VSL #3) as maintenance treatment has been shown to be effective in relapsing pouchitis in European trials. However, this agent has not been studied in the US, and its applicability in routine clinical practice has not been evaluated. AIM: To determine compliance and efficacy of probiotic treatment in patients with antibiotic-dependent pouchitis. METHODS: Thirty-one patients with antibiotic-dependent pouchitis were studied. VSL #3 is a patented probiotic preparation of live freeze-dried bacteria. All patients received 2 weeks of ciprofloxacin 500 mg b.d. followed by VSL #3 6 g/day for 8 months. Baseline Pouchitis Disease Activity Index scores were calculated. Patients' symptoms were reassessed at week 3 when VSL #3 therapy was initiated and at the end of the 8-month trial. Some patients underwent repeat pouch endoscopy at the end of the trial. RESULTS: All 31 patients responded to the 2-week ciprofloxacin trial with resolution of symptoms and they were subsequently treated with VSL #3. The mean duration of follow-up was 14.5+/-5.3 months (range: 8-26 months). At the 8-month follow-up, six patients were still on VSL #3 therapy, and the remaining 25 patients had discontinued the therapy due to either recurrence of symptoms while on treatment or development of adverse effects. All six patients who completed the 8-month course with a mean treatment period of 14.3+/-7.2 months (range: 8-26 months) had repeat clinical and endoscopic evaluation as out-patients. At the end of 8 months, these six patients had a mean Pouchitis Disease Activity Index symptom score of 0.33+/-0.52 and a mean Pouchitis Disease Activity Index endoscopy score of 1.83+/-1.72, which was not statistically different from the baseline Pouchitis Disease Activity Index endoscopy score of 2.83+/-1.17 (P=0.27). CONCLUSION: This study was conducted to evaluate bacteriotherapy in routine care. The use of probiotics has been adopted as part of our routine clinical practice with only anecdotal evidence of efficacy. Our review of patient outcome from the treatment placebo showed that only a minority of patients with antibiotic-dependent pouchitis remained on the probiotic therapy and in symptomatic remission after 8 months.

Melatonin in human preovulatory follicular fluid.

Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCH to stimulate follicle formation. Blood samples were obtained by venipuncture 30 min or less after follicular aspiration. All of the follicular fluids contained melatonin, in concentrations [36.5 +/- 4.8 (+/- SEM) pg/mL] substantially higher than those in the corresponding serum (10.0 +/- 1.4 pg/mL). A positive correlation was found between follicular fluid and serum melatonin levels in each woman (r = 0.770; P less than 0.001). These observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

The circadian rhythm of plasma melatonin during the normal menstrual cycle and in amenorrheic women.

Plasma melatonin, PRL, and LH levels were measured in samples collected every 2 h for 24 h from 14 normally cycling women during the early follicular, periovulatory, and luteal phases of their menstrual cycles. Plasma melatonin levels also were measured in samples collected at the same interval from 7 patients with hypothalamic amenorrhea. A distinct daily rhythm in plasma melatonin was evident in all subjects, with peaks occurring around 0300 h. Each woman's rhythm was remarkably consistent throughout the menstrual cycle (in terms of the phase, amplitude, and total melatonin secreted). Plasma PRL levels also exhibited daily rhythms which did not change during the menstrual cycle; the nocturnal peak plasma PRL level tended to occur 1-2 h after that for melatonin. Among the amenorrheic women, both daytime and nighttime melatonin levels were significantly higher (P less than 0.005) than in the normal women. Their plasma PRL levels were similar to those in the normal women. We conclude that, as for PRL, the circadian rhythm of melatonin secretion does not change significantly during the normal menstrual cycle. The elevated plasma melatonin levels in women with hypothalamic amenorrhea suggest that the hormone may be involved in the neuroendocrine pathology underlying this disorder.

A randomized clinical trial of ciprofloxacin and metronidazole to treat acute pouchitis.

Metronidazole is effective for the treatment of acute pouchitis after ileal pouch-anal anastomosis, but it has not been directly compared with other antibiotics. This randomized clinical trial was designed to compare the effectiveness and side effects of ciprofloxacin and metronidazole for treating acute pouchitis. Acute pouchitis was defined as a score of 7 or higher on the 18-point Pouchitis Disease Activity Index (PDAI) and symptom duration of 4 weeks or less. Sixteen patients were randomized to a 2-week course of ciprofloxacin 1,000 mg/d (n = 7) or metronidazole 20 mg/kg/d (n = 9). Clinical symptoms, endoscopic findings, and histologic features were assessed before and after therapy. Both ciprofloxacin and metronidazole produced a significant reduction in the total PDAI score as well as in the symptom, endoscopy, and histology subscores. Ciprofloxacin lowered the PDAI score from 10.1+/-2.3 to 3.3+/-1.7 (p = 0.0001), whereas metronidazole reduced the PDAI score from 9.7+/-2.3 to 5.8+/-1.7 (p = 0.0002). There was a significantly greater reduction in the ciprofloxacin group than in the metronidazole group in terms of the total PDAI (6.9+/-1.2 versus 3.8+/-1.7; p = 0.002), symptom score (2.4+/-0.9 versus 1.3+/-0.9; p = 0.03), and endoscopic score (3.6+/-1.3 versus 1.9+/-1.5; p = 0.03). None of patients in the ciprofloxacin group experienced adverse effects, whereas three patients in the metronidazole group (33%) developed vomiting, dysgeusia, or transient peripheral neuropathy. Both ciprofloxacin and metronidazole are effective in treating acute pouchitis with significant reduction of the PDAI scores. Ciprofloxacin produces a greater reduction in the PDAI and a greater improvement in symptom and endoscopy scores, and is better tolerated than metronidazole. Ciprofloxacin should be considered as one of the first-line therapies for acute pouchitis.

Azathioprine formulation optimizes metabolite profile in inflammatory bowel disease.

BACKGROUND: Recent studies have suggested that mercaptopurine metabolism is influenced by drug formulation (mercaptopurine vs. azathioprine) and concomitant use of 5-aminosalicylic acid medications. AIM: To determine the influence of dose, formulation and 5-aminosalicylic acid use on mercaptopurine metabolism. METHODS: Metabolites from 131 inflammatory bowel disease patients were analysed. Logistic regression was used to analyse correlations between dose and metabolite levels. Multivariate analysis was used to determine the effects of drug formulation and 5-aminosalicylic acid use. RESULTS: A positive correlation was detected between dose and 6-tioguanine nucleotides levels for azathioprine/Imuran formulation (P = 0.005) but not for mercaptopurine formulation. Adjusted mean 6-tioguanine nucleotides levels were similar for both formulations. Adjusted mean 6-methylmercaptopurine levels were higher for mercaptopurine formulation than for azathioprine formulation (1950 vs. 1056, P = 0.04). 5-Aminosalicylic acid use: 6-tioguanine nucleotides levels did not differ based on concomitant 5-aminosalicylic acid use. However, 5-aminosalicylic acid use did result in higher adjusted mean 6-methylmercaptopurine levels: 2078 on 5-aminosalicylic acid vs. 991 off 5-aminosalicylic acid (P = 0.004). CONCLUSIONS: (i) Azathioprine may have metabolic benefits by achieving a correlation of dose with 6-tioguanine nucleotides levels and by leading to lower mean 6-methylmercaptopurine levels. (ii) 5-aminosalicylic acid use does not significantly impact 6-tioguanine levels and may lead to higher 6-methylmercaptopurine levels.

Treatment of left-sided ulcerative colitis with butyrate enemas: a controlled trial.

BACKGROUND: The colonic mucosa is highly dependent upon the presence of luminal nutrients. This dependence is most marked in the distal colon. The major luminal nutrients are short chain fatty acids that are produced as a by-product of colonic fermentation of carbohydrates. Butyrate appears to be the short chain fatty acid most avidly metabolized by the colonic mucosa. It has been suggested that ulcerative colitis is, at least in part, related to an energy deficiency state of the colonic mucosa which may be secondary to impaired short chain fatty acid production, uptake or utilization. The objective of this study was to determine if butyrate given as enema therapy is effective in the treatment of active distal ulcerative colitis. METHODS: Thirty-eight patients with distal ulcerative colitis were randomly assigned to receive nightly butyrate (n = 19) or saline/placebo (n = 19) enemas. Butyrate enemas consisted of 60 mL of 80 mM sodium butyrate titrated to a pH of 7.0. Patients were assessed clinically and endoscopically at baseline and at 3 and 6 weeks follow-up. Pre- and post-treatment mucosal biopsies were assessed histologically. Response to therapy was determined by changes in a 12-point clinical disease activity index score based on patient symptoms, endoscopic mucosal appearance and physicians' global assessment. RESULTS: Clinical improvement was noted in seven of 19 (37%) butyrate-treated patients and nine of 19 (47%) placebo-treated patients (P = 0.51). Clinical remission was achieved in three patients in each group (16%). No toxicity was observed in either treatment arm. CONCLUSIONS: The results suggests that once nightly 60 mL butyrate enemas (80 mmol/L) are not efficacious in the treatment of distal ulcerative colitis.

Treatment of mildly to moderately active ulcerative colitis with a tryptase inhibitor (APC 2059): an open-label pilot study.

BACKGROUND: Mast cells isolated from the colonic mucosa in active ulcerative colitis appear to be partially degranulated, suggesting the release of tryptase. AIM: To investigate the safety and activity of APC 2059, a highly specific tryptase inhibitor, in the treatment of ulcerative colitis. METHODS: This was an open-label, Phase 2, multicentre pilot study in patients with mildly to moderately active ulcerative colitis, with a disease activity index of 6-9 on a 12-point scale. Fifty-six adults received 20 mg APC 2059 subcutaneously twice daily and 53 completed 28 days of treatment. The primary end-point was response, defined as a final disease activity index of < or = 3. Supplementary analyses were also performed. RESULTS: Sixteen (29%) of 56 patients responded. Five (9%) showed complete remission (disease activity index=0). Twenty-seven (49%) improved, with a final disease activity index of < or = 3 or a four-point reduction. Improvement or normalization in each category of the disease activity index was as follows: stool frequency, 64%; bleeding, 64%; endoscopy, 50%; physicians' rating, 63%. There were no significant relationships between outcome and pharmacokinetics. The most common adverse events were related to the injection site (32.1%). CONCLUSIONS: In this pilot study, the tryptase inhibitor APC 2059 was safe and there was evidence of activity in the treatment of ulcerative colitis.

Myofibroblastoma of the tunica testis: evolving phase of so-called fibrous pseudotumor?

A collagen-rich stromal tumor attached to the testicular tunica albuginea of a 22-year-old male is reported. Immunocytochemical and ultrastructural characterization revealed a predominant population of myofibroblasts, an as yet unrecognized observation in tumors arising from testicular tunics. The possible relationship with so-called fibrous pseudotumor (nodular fibrous proliferation) is discussed. The myofibroblastic nature of the cell population would support the hypothesis of a reactive contractile process if one accepts this tumor as an evolving phase of fibrous pseudotumor.

"Melatonin replacement therapy" for postmenopausal women: is it justified?

OBJECTIVE: Aging, sleep, and breast cancer are important concerns of postmenopausal women. There now is evidence that melatonin, the hormone secreted by the pineal gland, may have a role in the regulation of various human biological processes including sleep, tumor growth, and perhaps aging. The current knowledge concerning these questions is briefly and critically reviewed. CONCLUSIONS: Melatonin might be implicated in menopause-associated processes such as insomnia, breast cancer, and general aging. Its beneficial effect on sleep has been demonstrated in controlled clinical trials, however, "melatonin replacement therapy" for all postmenopausal women is currently unjustified.

d-Fenfluramine suppresses the increased calorie and carbohydrate intakes and improves the mood of women with premenstrual depression.

The ability of d-fenfluramine, a drug that releases brain serotonin and blocks its reuptake, to relieve premenstrual depression and excessive calorie and carbohydrate intakes was examined in 17 women with premenstrual syndrome. Subjects received d-fenfluramine (15 mg twice daily) or placebo, in random order, during the luteal phases of six menstrual cycles; ie, for three control and three treatment cycles each. Behavior was assessed with the Hamilton Rating Scale for Depression and its Addendum, and intakes of calories and nutrients were measured by allowing subjects unlimited access to isocaloric meal and snack foods rich in carbohydrates or protein. Pre-treatment follicular scores using the Hamilton Rating Scale for Depression and its Addendum were 2.0 +/- 0.5 and 0.5 +/- 0.5 (mean +/- SEM), respectively; corresponding luteal scores were 21.2 +/- 0.8 and 10.2 +/- 0.6 (P less than .0001). Luteal phase intakes of kilocalories, carbohydrates, and fats were also increased above follicular levels (P less than .01). d-Fenfluramine decreased premenstrual Hamilton Rating Scale for Depression and Addendum scores by 62% (P less than .001) and 60% (P less than .001), respectively; placebo reduced them by only 28% (P less than .02) and 30% (P less than .02). d-Fenfluramine also fully suppressed the premenstrual rise in kilocalorie, carbohydrate, and fat intakes (P less than .01).

Effects of melatonin on progesterone production by human granulosa lutein cells in culture.

OBJECTIVE: To test the hypothesis that melatonin modulates steroid synthesis in the human ovary. DESIGN: Granulosa lutein cells obtained from in vitro fertilization cycles were cultured in medium containing melatonin and human chorionic gonadotropin (hCG). RESULTS: Progesterone (P) secretion by granulosa lutein cells increased progressively in both basal and hCG-stimulated conditions, up to 96 hours in culture, plateaued at 144 and decreased thereafter. Melatonin (10(-7), 10(-9), 10(-11) M) had no effect on basal P or 17 beta-estradiol production. The addition of melatonin to the hCG-treated granulosa lutein cells significantly (P less than 0.05) potentiated the stimulatory effect of hCG on P production. The effect was most prominent after 144 and 196 hours of incubation. CONCLUSION: This observation suggests a role for melatonin in the intraovarian control of P production in the human ovary.

Effects of low-dose estrogen oral contraceptives on weight, body composition, and fat distribution in young women.

OBJECTIVE: To determine prospectively whether the use of low-dose estrogen oral contraceptives (OC) is associated with changes in weight, body composition, or fat distribution. DESIGN: Anthropometric measurements were performed in 49 healthy young (16 to 21 years old) women before commencement of OC use (30 micrograms ethinyl estradiol [EF2] plus 75 micrograms gestodene) and after three and six treatment cycles. Thirty one age- and weight-matched women who were not using OC served as controls. SETTING: Outpatient gynecological clinic of Hadassah Medical Center, a tertiary level hospital, and the "Shilo" voluntary service for the prevention of unwanted pregnancy. MAIN OUTCOME MEASURES: Anthropometric measurements included body mass index (BMI), waist-to-hip girth ratio, and body composition (the percentage of body fat and water), estimated by mean of infrared interactance. RESULTS: In the group of OC users, baseline BMI, percent fat, percent water, and waist-to-hip girth ratio were 21.1 +/- 0.32 (kg/m2), 23.8% +/- 0.63%, 57.4% +/- 0.39%, and 0.73 +/- 0.01, respectively, and did not change significantly after six cycles (20.6 +/- 0.41 [kg/m2], 23.9% +/- 0.57%, 58.1% +/- 0.49%, and 0.72 +/- 0.03, respectively). These measurements were not significantly different when compared with the nonusers. Fifteen OC users (30.6%) gained weight (> 0.5 kg). Weight gain was due to a significant accumulation of fat (from 22.5% +/- 1.1% to 25.6% +/- 0.74%), whereas the percentage of body water remained stable. The waist-to-hip girth ratio also was not changed significantly. Similarly, 11 nonusers (35.4%) gained weight because of similar nonabdominal fat accumulation. Ten OC users (20.4%) lost weight (57 kg +/- 1.51 to 55.4 +/- 1.47 [mean +/- SEM]) and 6 nonusers (19.3%) also lost weight (59 kg +/- 1.42 to 57.3 +/- 1.92). In both groups the loss of weight was not associated with significant change in body composition. CONCLUSIONS: The use of low-dose OC (EE2 plus gestodene) was not associated with overall impact on weight, body composition, or fat distribution. However, when weight gain did occur during OC use, it was due to increase in body fat and not in volume of body water, and it was not associated with changes in fat distribution.

Effects of hormone replacement therapy on weight, body composition, fat distribution, and food intake in early postmenopausal women: a prospective study.

OBJECTIVE: To evaluate the effects of hormone replacement therapy (HRT) on body weight and composition, fat distribution, and food intake in women entering the climacteric. DESIGN: Prospective clinical study. SETTING: Outpatient menopause clinic at a tertiary medical center. PARTICIPANTS: Sixty-three early postmenopausal women (44 to 54 years old) were prospectively studied for 1 year. They consisted of two groups: group A, 34 subjects who initiated continuous estrogen and progestin treatment (daily oral conjugated estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg), and group B, 29 women who refused hormonal therapy and served as controls. The age, menopausal status, initial anthropometric measurements (weight, body mass index [BMI], fat mass, and waist-to-hip girth ratio), and daily food intake (total caloric intake and food composition) were similar in both groups. INTERVENTIONS: Anthropometric measurements were performed before commencement of HRT use and after 12 months. MAIN OUTCOME MEASURES: Anthropometric measurements included BMI, waist-to-hip girth ratio, and body composition (the percentage of body fat and water) estimated by means of infrared interactance. Daily food intake was also recorded. RESULTS: The body weight and fat mass increased significantly in both the treatment (73.22 +/- 2.01 [mean +/- SE] to 75.57 +/- 1.12 kg) and the control group (71.45 +/- 3.11 to 73.51 +/- 1.23 kg). However, a significant shift from gynoid to android fat distribution was observed only in the control group (waist-to-hip ratio shifted from 0.80 +/- 0.01 to 0.85 +/- 0.01), whereas no significant change was observed in the treatment group (0.81 +/- 0.01 to 0.82 +/- 0.01). Caloric and macronutrient intake did not change in either group. CONCLUSIONS: These results indicate that continuous daily estrogen and progestin replacement therapy neither prevents nor increases early postmenopausal weight gain and fat accumulation. However, it does minimize the shift from gynoid to android fat distribution.

Periovulatory 17 beta-estradiol pattern in conceptional and nonconceptional cycles during menotropin treatment of anovulatory infertility.

The value of multiple parameters in the prediction of fertile cycles was prospectively evaluated in 52 menotropin-induced cycles. The periovulatory pattern of estradiol (E2) was found to correlate with conceptional cycles. E2 levels greater than 500 pg/ml on the day of human chorionic gonadotropin administration (day 0) with a further increase on day +1 (high ascending pattern--A1) were found to have a 51% predictive value for fertile cycles. Twelve of the 17 fertile cycles had an A1, type of response (71%), whereas the overall incidence of an A1 pattern was 42% (22 of 52). No pregnancies have occurred with preovulatory follicles less than or equal to 14 mm in diameter. The number of preovulatory follicles, E2 level on day 0, and midluteal progesterone had no predictive value for fertile cycles.

Precocious puberty following head injury. Case report.

A 6-year-old girl developed secondary sexual characteristics 5 months after severe closed head injury. Endocrinological tests confirmed a pubertal sexual condition; there was also diminution of serum melatonin and disruption of the diurnal pattern. Magnetic resonance imaging demonstrated focal hypothalamic injury; this is believed to be the first time such a posttraumatic lesion has been demonstrated by imaging techniques. The pathophysiology of this condition is discussed.