Early onset of primary hypogonadism revealed by serum anti-Mullerian hormone determination during infancy and childhood in trisomy 21

Male patients with an extra sex chromosome or autosome are expected to present primary hypogonadism at puberty owing to meiotic germ-cell failure. Scarce information is available on trisomy 21, a frequent autosomal aneuploidy. Our objective was to assess whether trisomy 21 presents with pubertal-onset, germ-cell specific, primary hypogonadism in males, or whether the hypogonadism is established earlier and affects other testicular cell populations. We assessed the functional status of the pituitary-testicular axis, especially Sertoli cell function, in 117 boys with trisomy 21 (ages: 2 months-20 year). To compare with an adequate control population, we established reference levels for serum anti-Mullerian hormone (AMH) in 421 normal males, from birth to adulthood, using a recently developed ultrasensitive assay. In trisomy 21, AMH was lower than normal, indicating Sertoli cell dysfunction, from early infancy, independently of the existence of cryptorchidism. The overall prevalence rate of AMH below the 3rd percentile was 64.3% in infants with trisomy 21. Follicle-stimulating hormone was elevated in patients <6 months and after pubertal onset. Testosterone was within the normal range, but luteinizing hormone was elevated in most patients <6 months and after pubertal onset, indicating a mild Leydig cell dysfunction. We conclude that in trisomy 21, primary hypogonadism involves a combined dysfunction of Sertoli and Leydig cells, which can be observed independently of cryptorchidism soon after birth, thus prompting the search for new hypotheses to explain the pathophysiology of gonadal dysfunction in autosomal trisomy.

Human choriogonadotropin prior to controlled ovarian stimulation and in vitro fertilization improves implantation, and pregnancy rates

Our purpose was to retrospectively compare controlled ovarian stimulation(COH) in IVF cycles with administration of hCG on the day of menses (D1-hCG) with women not receiving hCG at day 1 of menses (Control). Data on maternal age, endocrine profile, amount of rFSH required, embryo characteristics, implantation and pregnancy rates were recorded for comparison between D1-hCG (n = 36) and Control (n = 64). Dose of rFSH required to accomplish COH was significantly lower in D1-hCG. Following ICSI, more top-quality embryos were available for transfer per patient in the D1-hCG and biochemical pregnancy rates per transfer were significantly higher in the D1-hCG. Significantly higher implantation and on-going pregnancy rates per embryo transfer were observed in D1-hCG (64%) compared to Control (41%). Administration of D1-hCG prior to COH reduces rFSH use and enhances oocyte developmental competence to obtain top quality embryos, and improves implantation and on-going pregnancy rates. At present it is not clear if the benefit is related to producing an embryo that more likely to implant or a more receptive uterus, or merely fortuitous and related to the relatively small power of the study.

Association between ultrasound findings and extent of trophoblastic invasion into the tubal wall in ampullary pregnancy

Objective Predictive factors of damage to the Fallopian tube may guide the treatment of Patients with tubal pregnancy. The aim of the present study was to investigate the association between the depth of trophoblastic invasion into the tubal wall, assessed on postoperative histological examination, with the findings obtained on transvaginal sonograpby (TVS) in women with ampullary Methods Women with ampullary pregnancy undergoing salpingectomy were enrolled into the study. Only women with a finding of either an embryo with cardiac activity or a tubal ring on TVS were included in the analysis, a total of 8.5 patients. Trophoblastic invasion was assessed postoperatively and was histologically classified as Stage I when limited to the tubal mucosa, Stage II when extending to the muscle layer and Stage III in the case of complete tubal wall infiltration. The association between findings on TVS and the stage of trophoblastic invasion was evaluated. Results There was a significant association between the findings on TVS and the depth of trophoblastic invasion (P < 0.001). All patients in whom an embryo with cardiac activity bad been identified were found to have Stage II (17.9%) or Stage III (82.1%) invasion, whereas in those patients who showed a tubal ring on TVS, Stage I invasion was the most frequent finding (41.3%). Conclusions In ampullary pregnancy, the finding on TVS of an embryo with cardiac activity is associated with deeper penetration of trophoblastic tissue into the tubal wall than is the finding of a tubal ring. Copyright (C) 2009 ISUOG, Published by John Wiley & Sons, Ltd.

Hemostatic changes and clinical sequelae after on-pump compared with off-pump coronary artery bypass surgery: a prospective randomized study

Objective To delineate the effects of extracorporeal bypass on biomarkers of hemostasis, fibrinolysis, and inflammation and clinical sequelae. Methods Patients were assigned prospectively and randomly to either on-pump (n=41) or off-pump (n=51) coronary bypass surgery. The concentrations of C-reactive protein, fibrinogen, D-dimer, and plasminogen activator inhibitor type-1 in blood were quantified before and after (1 and 24 h) surgery. Similar surgical and anesthetic procedures were used for both groups. Clinical events were assessed during initial hospitalization and at the end of I year. Results The concentrations of plasminogen activator inhibitor type-1 and D-dimer were greater compared with preoperative values 1 and 24 h after surgery in both groups, but their concentrations increased to a greater extent 24 h after surgery in the on-pump group (P<0.01). The concentration of C-reactive protein did not change appreciably immediately after surgery in either group but increased in a parallel manner 24 h after either on-pump or off-pump surgery (P<0.01). Bypass surgery in the on-pump group was associated with greater blood loss during surgery and more bleeding after surgery (P <= 0.01). The incidence of all other complications was similar in the two groups. Conclusion On-pump surgery was associated with biochemical evidence of a prothrombotic state early after surgery but no greater incidence of thrombotic events was observed. The prothrombotic state might be a consequence of extracorporeal bypass, compensation in response to more bleeding, or both in patients undergoing on-pump surgery. Coron Artery Dis 20:100-105 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Additive Effects of Obstructive Sleep Apnea and Hypertension on Early Markers of Carotid Atherosclerosis

Obstructive sleep apnea (OSA) has emerged as an independent risk factor for atherosclerosis. However, OSA is frequently associated with several risk factors for atherosclerosis, including hypertension (HTN). The impact of OSA and HTN alone compared with the association of both conditions on carotid atherosclerosis is not understood. We studied 94 middle-aged participants free of smoking and diabetes mellitus who were divided into 4 groups: controls (n = 22), OSA (n = 25), HTN (n = 20), and OSA + HTN (n = 27). All of the participants underwent polysomnography and carotid measurements of intima-media thickness, diameter, and distensibility with an echo-tracking device. Compared with controls, intima-media thickness and carotid diameter were similarly higher in OSA (713 +/- 117 and 7117 +/- 805 mu m), and HTN groups (713 +/- 182 and 7191 +/- 818 mu m), with a further significant increase in OSA + HTN patients (837 +/- 181 and 7927 +/- 821 mu m, respectively; P < 0.01). Carotid distensibility was significantly lower in HTN (P < 0.05) and OSA + HTN subjects (P < 0.001) compared with controls. In the OSA + HTN group, carotid distensibility was significantly lower than in the OSA group and controls (P < 0.05 for each comparison). Multivariate analysis showed that intima-media thickness was positively related to systolic blood pressure and apnea-hypopnea index. Apnea-hypopnea index was the only factor related to carotid diameter. Age and systolic blood pressure were independently related to carotid distensibility. In conclusion, the association of OSA and HTN has additive effects on markers of carotid atherosclerosis. Because early markers of carotid atherosclerosis predict future cardiovascular events, including not only stroke but also myocardial infarction, these findings may help to explain the increased risk of cardiovascular disease in patients with OSA. (Hypertension. 2009; 53: 64-69.)

Effects of ambient levels of air pollution generated by traffic on birth and placental weights in mice

Objective: To examine whether there is an association between fetal and/or placental weight and exposure to ambient levels of air pollution in mice. Design: Chronic experiments on mice that were exposed to polluted vs. clean air. Setting: Environmental exposure to atmospheric pollution. Animal(S): Female Swiss mice (n = 70) were maintained at different stages of gestation in an exposure chamber located at an intersection with heavy traffic in a major city in Brazil. Control mice were maintained in a similar chamber, located adjacent to the exposure chamber but equipped with filters for particles and reactive gases. Intervention(s): Animals were divided into six groups as follows: no exposure, exposure to a polluted chamber throughout gestation, exposure to a polluted chamber during the 1st week of pregnancy, exposure to a polluted chamber during the 2nd and 3rd weeks, exposure to a polluted chamber during the 1st and 2nd week, and exposure to a polluted chamber during the 3rd week. Main Outcome Measure(S): At the end of the gestational period, the determination of fetal and placental weight was performed after cesarean section. Result(s): Exposure to air pollution during the 1st week of pregnancy promoted a significant reduction in fetal weight. Mice exposed to polluted air, in any phase of gestation, presented with lower placental weight in comparison to mice maintained in clean chambers. Conclusion(s): Exposure to ambient levels of traffic pollution at early phases of gestation is a determinant for decreased final fetal weight. Placental weight is reduced with exposure to air pollution at any phase of gestation. (Fertil Steril (R) 2008;90:1921-4. (C)2008 by American Society for Reproductive Medicine.)

Trans-resveratrol inhibits early blood vessel formation (Vasculogenesis) without impairment of embryonic growth

Resveratrol is a stilbene compound found in grapes and other sources. In this study we examined the effects of trans-resveratrol (4.38-438 mu M/implant) in the vasculogenesis of yolk-sac membranes and its capacity to improve chick embryo growth. High concentrations of the stilbene (43.8-438 mu M) significantly inhibited early vessel formation, decreasing the percentage vitelline vessels of 3.5-day embryos by 50% compared to the control. In addition, basic fibroblast growth factor-stimulated vasculogenesis (140% of vessels as compared to control) was partially reversed by t-resveratrol (35% of inhibition) and treatments with cyclooxygenase inhibitors (acetylsalicylic acid and indomethacin) as well a protein-kinase C (PKC) activator (phorbol-12,13-dibutyrate) decreased the vessel number to 60%, 50%, and 44%, respectively. Treatments with t-resveratrol (4.38-43.8 mu M/implant) significantly increased the body length of embryos incubated in vitro uncoupled from any impairment in the body shape or detectable embryotoxic effect. We suggest that the antivasculogenic activity and the enhancement in embryonic growth promoted by non acute treatments with t-resveratrol were, at least in part, due to PKC inhibition. We suggest that t-resveratrol can be usable not only as a reliable functional nutriment, but also is useful for the development of prophylactic and/or therapeutic agents for treatment of angiogenic-degenerative diseases.

Scanning laser polarimetry with enhanced corneal compensation for detection of axonal loss in band atrophy of the optic nerve

PURPOSE: To compare the abilities of scanning laser polarimetry (SLP) with enhanced corneal compensation (ECC) and variable corneal compensation (VCC) modes for detection of retinal nerve fiber layer (RNFL) loss in eyes with band atrophy (BA) of the optic nerve. DESIGN. Cross-sectional study. METHODS: Thirty-seven eyes from 37 patients with BA and temporal visual field defect from chiasmal compression and 40 eyes from 40 healthy subjects were studied. Subjects underwent standard automated perimetry and RNFL measurements using an SLP device equipped with VCC and ECC. Receiver operating characteristic (ROC) curves were calculated for each parameter. Pearson correlation coefficients were obtained to evaluate the relationship between RNFL thickness parameters and severity of visual field loss, as assessed by the temporal mean defect. RESULTS: All RNFL thickness parameters were significantly lower in eyes with BA compared with normal eyes with both compensation modes. However, no statistically significant differences were observed in the areas under the ROC curves for the different parameters between GDx VCC and ECC (Carl Zeiss Meditec, Inc, Dublin, California, USA). Structure-function relationships also were similar for both compensation modes. CONCLUSIONS: No significant differences were found between the diagnostic accuracy of GDx ECC and that of VCC for detection of BA of the optic nerve. The use of GDx ECC does not seem to provide a better evaluation of RNFL loss on the temporal and nasal sectors of the peripapillary retina in subjects with BA of the optic nerve.

Protective Effect of N-acetylcysteine on Early Outcomes of Deceased Renal Transplantation

We investigated the effects of the antioxidant N-acetylcysteine (NAC) on early outcomes of deceased donor renal transplantation. Between April 2005 and June 2008, adult primary graft recipients of deceased renal donors were assigned to treatment (n = 38) or control (n = 36) groups and evaluated for 90 days and one year after renal transplantation. The treatment group received NAC orally (600 mg twice daily) from day 0 to 7 postoperatively. Renal function was determined by serum creatinine, MDRD and Cockcroft-Gault estimated GFR (eGFR), delayed graft function (DGF) and dialysis free Kaplan-Meier estimate curve. Serum levels of thiobarbituric acid reactive substances (TBARS), were employed as markers of oxidative stress. The NAC group displayed a lower mean serum creatinine during the first 90 days (P = .026) and at 1 year after transplantation (P = .005). Furthermore, the NAC group showed a higher mean eGFR throughout the first 90 days and at 1 year. DGF was lower among the NAC group (P = .017) and these recipients required fewer days of dialysis (P = .012). Oxidative stress was significantly attenuated with NAC (P < .001). Our results suggested that NAC enhanced early outcomes of deceased donor renal transplantation by attenuating oxidative stress.

The effect of early virological response in health-related quality of life in HCV-infected patients

Twenty-nine HCV-infected patients were treated with pegylated interferon alpha. Diagnosis was based on serum HCV RNA-PCR positive results and liver biopsy. All patients had elevated serum levels of alanine aminotransferase at the time of the study, but liver disease was compensated. Patients were evaluated at baseline treatment and after 4 and 12 weeks of antiviral treatment with the Medical Outcomes Study 36-item Short-Form Health Survey. The Mini-International Neuropsychiatric Interview was used to exclude previous or current psychiatric diagnoses. Both patients and psychiatrists were blind to the HCV RNA status, and serum HCV RNA test results only became available after the visit at week 12. After antiviral treatment, 16 patients (55.2%) were classified as nonresponders and 13 (44.8%) were classified as responders. When compared to nonresponders, responders had a greater improvement in the HRQOL scores for the mental health domain (P<.019). Differences in other domains were not significant. The present study confirms that active viral infection is one possible reason for the poor Health-Related Quality of Life in this population.

Enterohormonal changes after digestive adaptation: Five-year results of a surgical proposal to treat obesity and associated diseases

Background Recent physiological knowledge allows the design of bariatric procedures that aim at neuroendocrine changes instead of at restriction and malabsorption. Digestive adaptation is a surgical technique for obesity based in this rationale. Methods The technique includes a sleeve gastrectomy, an omentectomy and a jejunectomy that leaves initial jejunum and small bowel totaling at least 3 m (still within normal variation of adult human bowel length). Fasting ghrelin and resistin and fasting and postprandial GLP-1 and PYY were measured pre- and postoperatively. Results Patients: 228 patients with initial body mass index (BMI) varying from 35 to 51 kg/m(2); follow-up: I to 5 years; average EBMIL% was 79.7% in the first year; 77.7% in the second year; 71.6% in the third year; 68.9% in the fourth year. Patients present early satiety and major improvement in presurgical comorbidities, especially diabetes. Fasting ghrelin and resistin were significantly reduced (P<0.05); GLP-1 and PYY response to food ingestion was enhanced (P<0.05). Surgical complications (4.4%) were resolved without sequela and without mortality. There was neither diarrhea nor detected malabsorption. Conclusions Based on physiological and supported by evolutionary data, this procedure creates a proportionally reduced gastrointestinal (GI) tract that amplifies postprandial neuroendocrine responses. It leaves basic GI functions unharmed. It reduces production of ghrelin and resistin and takes more nutrients to be absorbed distally enhancing GLP-1 and PYY secretion. Diabetes was improved significantly without duodenal exclusion. The patients do not present symptoms nor need nutritional support or drug medication because of the procedure, which is safe to perform.