Serum and follicular fluid hormone levels during in vitro fertilization after short- or long-course treatment with a gonadotropin-releasing hormone agonist.

OBJECTIVE: To examine the impact of flare (short) vs. down-regulation (long) GnRH agonist (GnRH-a) on serum and follicular fluid (FF) LH and androgen concentrations in women undergoing IVF treatment cycles. DESIGN: Prospective observational study. SETTING: IVF clinic. PATIENT(S): One hundred sixteen ovulatory subjects undergoing IVF. INTERVENTION(S): Fifty-eight ovulatory patients undergoing a down-regulation regimen matched with 58 undergoing the flare regimen as part of an IVF cycle. MAIN OUTCOME MEASURE(S): Serum concentrations of LH, FSH, Progesterone (P4), Androstenedione (A), T, and E(2) on the day of hCG administration were compared between the two groups. In addition, the FF P4, 17OHP4, A, T, and E(2) levels were compared in the two groups. RESULT(S): Serum LH was significantly higher with the flare regimen (15.2 +/- 1.14 IU/L, P<.05) when compared with results with the down-regulation protocol (9.5 +/- 0.77 IU/L). In addition, FF A was significantly higher in the flare protocol (57.3 +/- 13.3 ng/mL, P<.05) compared with in the down-regulation protocol (27 +/- 2.44 ng/mL). Serum and FF P4, 17OH P4, T, and E(2) were not statistically significantly different between the two groups. CONCLUSION(S): Serum LH and FF A are significantly higher in the flare regimen in comparison with the down-regulation regimen. Circulating LH appears to play a role in determining FF A concentration.

Release of a soluble ATPase from the rabbit isolated vas deferens during nerve stimulation.

The properties of the ATPase released during electrical field stimulation (EFS) (8 Hz, 25 s) of the sympathetic nerves of the superfused rabbit isolated vas deferens were investigated. Superfusate collected during EFS rapidly metabolised exogenous ATP (100 microM) and 50% was broken down in 5.67+/-0.65 min. The main metabolite was ADP, virtually no AMP was produced and adenosine was absent. No enzyme activity was seen in samples collected in the absence of EFS. Lineweaver-Burke analysis of the initial rates of ATP hydrolysis gave a K(M) of 40 microM and V(max) of 20.3 nmol ATP metabolized min(-1) ml(-1) superfusate. ATPase activity was unaffected by storage at room temperature for 24 h, but was abolished at pH4 or by heating at 80 degrees C for 10 min. ARL 67156 inhibited ATP breakdown in a concentration-dependent manner (IC(50)=25 microM (95% confidence limits=22-27 microM), Hill slope=-1.06+/-0.04). When EFS was applied three times at 30 min intervals, ATP metabolism was 20-30% less in superfusate collected during the second and third stimulation periods compared with the first. ATPase activity was released in a frequency-dependent manner, with significantly greater activity seen after stimulation at 4 and 8 Hz than at 2 Hz. In conclusion, EFS of the sympathetic nerves in the rabbit vas deferens causes release of substantial ATPase, but little ADPase activity into the extracellular space. This contrasts with the guinea-pig vas deferens, which releases enzymes that degrade ATP to adenosine. Thus, the complement of enzymes released by nerve stimulation is species-dependent.

Complications of hysteroscopic surgery: predicting patients at risk.

OBJECTIVE: To determine the frequency of operative complications and whether they can be predicted by specific patient characteristics or type of hysteroscopic procedure. METHODS: We collected demographic and medical history information on 925 women who had hysteroscopies from 1995 through 1996. We compared differences in rates of operative complications of specific hysteroscopic procedures. Operative complications were defined as uterine perforation, excessive glycine absorption (1 L or more), hyponatremia, hemorrhage (500 mL or more), bowel or bladder injury, inability to dilate the cervix, and procedure-related hospital admissions. RESULTS: Operative complications occurred in 25 (2.7%) of 925 hysteroscopies. Excessive fluid absorption was the most frequent complication. Hysteroscopic myomectomy and resection of uterine septum were associated with greater odds of complications (odds ratio [OR] 7.4, 95% confidence interval [CI] 3.3, 16.6 and OR 4.0, 95% CI 0.9, 19.6, respectively). Hysteroscopic polypectomy and endometrial ablation were associated with lower odds of complications (OR 0.1, 95% CI 0.0, 0.7 and OR 0.4, 95% CI 0.1, 3.3, respectively). Hysteroscopies done by reproductive endocrinologists and preoperative GnRH agonist therapy were associated with 4-7 times higher odds for operative complications. CONCLUSION: Complications during hysteroscopic surgery are rare. Among hysteroscopic procedures, myomectomies and resections of uterine septa have significantly higher rates of complications, especially excessive fluid absorption. Meticulous fluid management might limit the number of serious complications of these higher-risk procedures.

A case-control study of galactose consumption and metabolism in relation to ovarian cancer.

Consumption or metabolism of dairy sugar and ovarian cancer have been linked based on evidence that galactose may be toxic to ovarian germ cells and that ovarian cancer is induced in animals by depletion of oocytes. We assessed consumption of dairy products and obtained blood for biochemical and molecular genetic assessment of galactose metabolism in 563 women with newly diagnosed epithelial ovarian cancer and 523 control women selected either by random digit dialing or through lists of residents in eastern Massachusetts and New Hampshire. We observed no significant differences between cases and controls in usual consumption of various types of dairy products or total daily lactose (the principal source of galactose in the diet); nor did we find that RBC activity of either galactose-1-phosphate uridyl transferase (GALT) or galactokinase differed. The mean (and SE) activity of uridine diphospho-galactose 4'-epimerase (in micromoles per hour per gram of hemoglobin) was, however, significantly lower (P < 0.005) in cases compared with controls, 20.32 (0.31) versus 21.64 (0.36). Ovarian cancer cases were also more likely to carry the N314D polymorphism of the GALT gene, generally predisposing to lower GALT activity. The difference was most evident for endometrioid and clear cell types of ovarian cancer, in which 3.9% of cases were found to be homozygous for N314D compared with 0.4% of controls, yielding an odds ratio and 95% confidence interval of 14.17 (2.62-76.60). We conclude that, whereas adult consumption of lactose carries no clear risk for the disease, certain genetic or biochemical features of galactose metabolism may influence disease risk for particular types of ovarian cancer.

Predictive value of serum and follicular fluid leptin concentrations during assisted reproductive cycles in normal women and in women with the polycystic ovarian syndrome.

Leptin is an adipocyte-derived hormone which plays a central role in the regulation of body weight and energy homeostasis and in signalling to the brain that adequate energy stores are available for reproduction. Although leptin may affect reproduction by regulating the hypothalamic-pituitary-gonadal axis, recent in-vitro observations indicate that leptin may also have direct intra-ovarian actions. Leptin concentrations were measured in women who succeeded in becoming pregnant within three cycles of in-vitro fertilization (IVF) or gamete intra-fallopian transfer (n = 53), in women who failed to become pregnant within three cycles (n = 50), and in women with polycystic ovarian syndrome (PCOS) (n = 22). It was found that lower follicular fluid leptin concentrations were a marker of assisted reproduction treatment success in normal women. Women with PCOS had higher leptin concentrations than women without such a diagnosis, but this was due to their higher body mass index (BMI). After adjustment for age and BMI, women with PCOS who became pregnant tended to have lower mean follicular fluid leptin concentrations than women with PCOS who did not succeed at becoming pregnant. Further studies exploiting the strengths of the IVF model are needed to assess whether the prognostic role for follicular fluid leptin in human reproduction is independent of other factors, and to elucidate the underlying mechanisms.

Recent trends in assisted reproductive techniques and associated outcomes.

OBJECTIVE: We examined recent trends in success rates for assisted reproduction and determined the influence of changes in patient selection and treatment characteristics on these trends. METHODS: We collected baseline information and abstracted treatment-related details and outcomes on 1244 couples accepted for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) at three clinics in greater Boston from 1994-1998. RESULTS: Delivery rates per initiated cycle improved significantly from 14.9% for IVF and 20.6% for GIFT in 1994-1995 to 22.5% for IVF and 28.0% for GIFT in 1997-1998 (P < or = .001). After adjusting for female age, the two treatment-related variables that appeared most likely to explain this trend were decreased use of GnRH agonists in short course (flare) regimens and increased use of highly purified forms of urinary gonadotropins. CONCLUSION: There were significant improvements in the success rates for IVF and GIFT from 1994-1998 that correlated with changes in ovulation induction regimens.

Psychosocial skills training for schizophrenia: lessons from the laboratory.

A large body of research supports the efficacy of psychosocial treatments for schizophrenia, particularly learning-based therapies. The Schizophrenia Patient Outcomes Research Team recommended that cognitive-behavioral therapies be used in schizophrenia, and skills training was included in the practice guideline for treating patients with schizophrenia published by the American Psychiatric Association. This article provides an updated review of empirical studies of psychosocial skills training, showing its value in treating patients with schizophrenia as well as its broader clinical effectiveness. Data supporting the efficacy of psychosocial skills training continue to accumulate. Such programs should continue to be included in best practices guidelines and treatment recommendations for schizophrenia. Future clinical service research could be directed toward integration of skills training with other psychosocial treatment methods.

Gonadotropin-releasing hormone agonist use in assisted reproduction cycles: the influence of long and short regimens on pregnancy rates.

OBJECTIVE: To compare the efficacy of GnRH agonists used in either the flare (short) or down-regulation (long) regimen as part of IVF or GIFT treatment cycles. DESIGN: Observational study. SETTING: Three IVF clinics. PATIENT(S): One thousand two hundred forty-four couples accepted for IVF or GIFT treatment at participating clinics. INTERVENTION(S): In vitro fertilization or GIFT protocols standard to each clinic were recorded. MAIN OUTCOME MEASURE(S): Treatment cycle characteristics and outcomes, including E2 level, number of oocytes retrieved, and clinical pregnancy rate. RESULT(S): At site 1, there were 146 clinical pregnancies in 980 flare cycles, for a pregnancy rate of 14.9%, compared with 148 clinical pregnancies in 650 down-regulation cycles, for a pregnancy rate of 22.8%. This difference persisted after adjustment for age, primary infertility diagnosis, GIFT or IVF therapy, and year of treatment, and appeared to be mediated largely by the number of oocytes retrieved (mean, 9.8 for downregulation and 8.7 for flare in the first cycle). Despite having fewer oocytes retrieved, women who received flare regimens had higher E2 levels before hCG administration. CONCLUSION(S): Women who received GnRH agonists in a flare regimen had 11% fewer oocytes retrieved and a 35% reduction in the clinical pregnancy rate compared with those who received them in a down-regulation regimen; this difference was not explained by patient selection factors.

Genital talc exposure and risk of ovarian cancer.

Epidemiologic studies have suggested an increased risk for ovarian cancer associated with the use of talcum powder in genital hygiene, but the biologic credibility of the association has been questioned. We conducted a population-based case-control study in eastern Massachusetts and New Hampshire involving 563 women with newly diagnosed epithelial ovarian cancer and 523 control women selected either by random digit dialing or through lists of residents. Use of body powders was assessed through personal interview and the exposure odds ratio (OR) for the use of talc in genital hygiene was calculated. Cases were more likely than controls (45% vs. 36%) to have used talc as a body powder in some manner, and the excess was confined to patients who used talc on the perineum directly or as a dusting powder to underwear or sanitary napkins. Relative to women who never used body powder or used it only in non-genital areas, the OR (and 95% confidence interval) associated with genital exposure to talc was 1.60 (1.18 and 2. 15) after adjustment for age, study location, parity, oral contraceptive use, body mass index and family history of breast or ovarian cancer. Exposure prior to rather than after a first livebirth appeared to be more harmful, and the association was most apparent for women with invasive serous cancers and least apparent for those with mucinous tumors. We conclude that there is a significant association between the use of talc in genital hygiene and risk of epithelial ovarian cancer that, when viewed in perspective of published data on this association, warrants more formal public health warnings.

Basal hormone levels in women who use acetaminophen for menstrual pain.

OBJECTIVE: To compare basal gonadotropin and estradiol levels between women using acetaminophen versus those using no or other types of analgesics. DESIGN: Observational study. SETTING: Three IVF clinics in greater Boston. PATIENT(S): Three hundred eighty-six women accepted for their first IVF treatment who completed questionnaires recording medical history, including analgesic use for menstrual pain, and who had blood drawn during the menstrual phase of a cycle before treatment. MAIN OUTCOME MEASURE(S): Basal FSH, LH, and estradiol. RESULT(S): Basal hormone levels, especially LH, were lower for women who regularly used acetaminophen compared with women who used no medication or other types of analgesics. Lower hormone levels in acetaminophen users were consistently observed when women were subdivided by age, body mass index, smoking history, and degree of menstrual pain-features that might have influenced analgesic use or hormone levels. CONCLUSION(S): This study provides preliminary evidence that acetaminophen may lower gonadotropin and estradiol levels and offers a biologic basis for the epidemiologic observation that acetaminophen use may reduce the risk of ovarian cancer.

Diffuse histiocytic lymphoma treated with chemotherapy and radiation.

A case of cutaneous lymphoma treated aggressively with chemotherapy and radiation is presented. This case is particularly interesting due to the fact that the patient also had a history of a malignant melanoma removed from the right shoulder, 1.26 mm thick, invasive to level III. He had two subsequent right axillary node tumors and a mesenteric tumor removed, all revealing metastatic malignant melanoma.

Ventilation parameters and arterial blood gases as a prediction of hypoplasia in congenital diaphragmatic hernia.

Attempts to predict the degree of pulmonary hypoplasia associated with congenital diaphragmatic hernia have been made by evaluating the ventilation parameters and the arterial blood gasses of these patients. A CO2 index as a predictor of outcome, which correlates the PaCO2 with the ventilation index, was recently proposed. However, in this study the postductal PaO2 was a better predictor of survival. And the so-called "honeymoon period" was a better indicator of the efficacy of extracorporeal membrane oxygenation (ECMO) than the CO2 index. Nineteen patients were evaluated; 11 were treated with ECMO, and eight were not considered suitable for ECMO.

Glass ionomer cement restorations: the effects of lasing the cavity walls on marginal microleakage.

Glass Ionomer cements are used in modern dentistry for various preventive purposes, one of which is the treatment of cervical caries lesions. Anticariogenic properties and the ability to bond to dentin and enamel are their main advantages. Since acid-etching of the tooth prior to glass ionomer placement is contraindicated, a "dry" defocused laser beam was used to enhance retention. The results indicate that finishing the cavity walls with a laser beam increased the marginal microleakage of the glass ionomer cement restorations. Thus, the procedure was apparently found unsuitable for clinical use.

Clinical use of extracorporeal membrane oxygenation in the treatment of persistent pulmonary hypertension following surgical repair of congenital diaphragmatic hernia.

The clinical use of extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension following surgical repair of congenital diaphragmatic hernia is reported on 11 patients. The patients had a total of 13 treatments; two patients had two treatments. During the same period of clinical use, 122 patients were placed on ECMO for all causes. The indications, results, and complications of the use of ECMO for treatment following surgical repair of congenital diaphragmatic hernia are presented. The reversal of persistent pulmonary hypertension is demonstrated. All patients treated by ECMO for congenital diaphragmatic hernia have survived.

Adhesion of composite materials to enamel: comparison between the use of acid and lasing as pretreatment.

Acid-etch is presently the accepted method for adhesion of composite materials to enamel. In this investigation, we used the laser for pretreatment of the enamel instead of acid. The adhesive (tensile) strength was measured by the Instron unit and statistically analyzed. Results demonstrated that bonding strength following laser pretreatment is comparable to that of acid-etch.

The treatment of heroin addiction: naltrexone alone and with behavior therapy.

Recently, narcotic antagonists (drugs which block the euphoric effects of opiates) and behavior therapy have both been proposed as possible treatments for heroin addiction. In the present study the effectiveness of one particular antagonist, naltrexone, was examined under two conditions: (1) when administered alone, and (2) when administered in conjunction with behavior therapy. Measures of treatment effect included number of days on naltrexone, number of weeks in the program, reported side effects, and number of dirty urines in each treatment. While data initially indicated a superiority of the combined treatment program, this superiority faded over time. Results are discussed in terms of program start-up effects (especially when using experimental drugs), terms of process versus outcome measurement, and in terms of societal pressure operating against the success of heroin treatment in minority populations with poor job skills.