Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome

OBJECTIVE: To evaluate the effects of metformin administration on spontaneous LH episodic release in a group of nonobese polycystic ovary (PCOS) patients. DESIGN: Controlled clinical study. SETTING: PCOS patients in a clinical research environment. PATIENT(S): Twenty nonobese PCOS patients were enrolled after informed consent. INTERVENTION(S): All patients underwent hormonal evaluations and a pulsatility study (sampling every 10 minutes for 4 hours) before and at the sixth month of therapy (metformin, 500 mg, p.o. b.i.d.). Ultrasound examinations and Ferriman-Gallwey scoring were also performed. MAIN OUTCOME MEASURE(S): Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17-hydroxy-progesterone (17-OHP), and testosterone (T), glucose, insulin, and C-peptide concentrations. RESULT(S): After 6 months of metformin administration, the plasma LH, 17-OHP, A, and T levels and LH/FSH ratio were significantly reduced. Insulin sensitivity, expressed as the glucose-to-insulin ratio, was significantly improved under glucose load after 6 months of treatment. Spontaneous LH episodic release showed a significant reduction in pulse amplitude with no changes in pulse frequency. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic women. The ovarian volume and Ferriman-Gallwey scores also were significantly reduced. CONCLUSION(S): Metformin administration improves reproductive axis functioning in hyperandrogenic nonobese PCOS patients. By acting on the ovary and restoring normal ovarian activity, metformin positively modulates the reproductive axis (namely GnRH-LH episodic release).     

Identification of meiotic anomalies with multiplex fluorescence in situ hybridization: Preliminary results

OBJECTIVE: To characterize meiotic anomalies in infertile men by multiplex fluorescence in situ hybridization (M-FISH) and to determine whether synaptic problems affect specific bivalents or whether anomalies are random. DESIGN: Analysis of meiotic preparations with standard techniques and M-FISH. SETTING: Assisted reproduction centers and Universitat Autònoma de Barcelona. PATIENT(S): Three fertile men undergoing vasectomy, four sterile patients with oligoasthenoteratozoospermia, and one patient with a Robertsonian translocation t(13;14). INTERVENTION(S): Unilateral testicular biopsy in controls and patients with oligoasthenoteratozoospermia and collection of a semen sample from the translocation carrier. MAIN OUTCOME MEASURE(S): Identification of bivalents in metaphase I and chromosomes in metaphase II and characterization of chromosome abnormalities. RESULT(S): All bivalents in metaphase I and all chromosomes in metaphase II could be identified. In controls and in one patient with oligoasthenoteratozoospermia, meiosis was normal. Other patients with oligoasthenoteratozoospermia showed different types of anomaly: desynapsis, breaks, precocious XY separation, or cryptic reorganizations. The Robertsonian translocation t(13;14) was easily identified. CONCLUSION(S): Results confirm the high incidence of synaptic errors in oligoasthenoteratozoospermia patients. Bivalents in metaphase I and chromosomes in metaphase II were individually identifiable. Nondisjunctional errors or small reorganizations overlooked in classic meiotic preparations were identified. Synaptic anomalies seem to affect meiotic bivalents at random.     

Intraventricular hemorrhage and periventricular leukomalacia in preterm infants

OBJECTIVE: To evaluate whether intraventricular hemorrhage and periventricular leukomalacia are characterized by different risk factors. METHODS: In a cohort of 653 consecutive singleton neonates born after preterm membrane rupture, spontaneous preterm labor, or indicated preterm delivery at 24 to 33 weeks of gestation from January 1, 1993, to December 31, 2002, we evaluated the obstetric and histopathologic placental variables in reference to the development of intraventricular hemorrhage (n = 44), periventricular leukomalacia (n = 19), or no ultrasonographic cerebral lesion (n = 589). Excluded were stillbirths and congenital anomalies. Statistical analysis included Fisher exact test, Student t test, and stepwise logistic regression analysis with a 2-tailed P <.05 considered significant. RESULTS: Multivariate analysis showed that occurrence of neonatal intraventricular hemorrhage and periventricular leukomalacia were associated only with spontaneous prematurity (odds ratio = 1.9; 95% confidence interval 1.1-3.4) and gestational age at delivery in weeks (odds ratio = 0.8; 95% confidence interval 0.7-0.9). Neonates with intraventricular hemorrhage did not differ from those with periventricular leukomalacia in any obstetric or neonatal variable, but there was a higher risk of neurodevelopmental delay associated with periventricular leukomalacia. CONCLUSION: Among premature infants born at less than 34.0 weeks of gestation, intraventricular hemorrhage and periventricular leukomalacia share common clinical characteristics, with spontaneous preterm delivery and gestational age at delivery as the only independent antenatal predictors.     

Second-trimester diagnosis of intracranial vascular anomalies in a fetus with subdural hemorrhage

OBJECTIVES: Risk factors for intracranial hemorrhage occurring in prenatal life are imperfectly known. A case of prenatal diagnosis of subdural hemorrhage associated with multiple intracranial vascular aneurysms is described. METHODS: Sonography and magnetic resonance imaging of the fetal head were obtained at 21 weeks' gestation and compared with pathologic findings. RESULTS: Sonography showed a large transonic mass displacing the normal intracranial structures. Magnetic resonance imaging demonstrated the hemorrhagic origin of the mass and showed multiple vascular anomalies. Postmortem examination confirmed the compression of the cerebral hemisphere by a blood collection, probably because of bleeding from one of the multiple vascular aneurysms into the subdural space. CONCLUSION: Magnetic resonance imaging with the use of single-shot ultrafast sequences may be useful not only in the differential diagnosis of fetal intracranial hemorrhage but also in identifying vascular risk factors.     

Maternal anaphylaxis and fetal brain damage after intrapartum chemoprophylaxis

We report a case of maternal anaphylaxis following intrapartum chemoprophylaxis. The term fetus developed severe brain damage as a consequence of intrapartum asphyxia. The lesions resulted from maternal hypotension following anaphylaxis. We discuss the feto-maternal risks and the controversial treatment of such a condition. The increasing number of penicillin-treated parturients will result in further cases of maternal anaphylaxis than previously found.     

Treatment of acute biliary pancreatitis: our experience

The results of endoscopic and surgical treatment in 21 patients affected by acute biliary pancreatitis are reported. All patients were managed according to the same protocol. Once the diagnosis was formulated (pain, serum amylase, ultrasonography, cholestasis and/or cholangitis) and the severity evaluated (Ranson's criteria, glucose and urea levels), the 21 patients underwent endoscopic retrograde cholangiopanctratography--within 24 hours in 8 patients (predicted severe disease) or within 72 hours in 13 patients (predicted mild disease). Endoscopic sphincterotomy was performed in 18 patients with stones in the common bile duct and was successful in 94.5% (17 patients: 3 patients underwent more than one session to confirm or achieve clearance of the duct). The morbidity rate associated with endoscopic sphincterotomy was 16% (3 patients: 2 haemorrhages, 1 perforation). There were no deaths. Cholecystectomy was performed in 16 patients within 2-9 weeks of the initial attack of acute biliary pancreatitis. There were 3 minor complications (respiratory, laparotomy, urinary infection), no major intraoperative or postoperative morbidity, and no mortality. Acute biliary pancreatitis is still associated with significant morbidity and mortality, but can be managed safely with combined medical, endoscopic and surgical treatment.     

Left ventricular mass monitoring in the follow-up of dialysis patients: prognostic value of left ventricular hypertrophy progression

BACKGROUND: Regression of left ventricular hypertrophy (LVH) in the setting of a well-planned intervention study has been associated with longer survival in hemodialysis patients. Whether changes in left ventricular mass (LVM) in clinical practice predict survival and cardiovascular events in these patients is still unknown. METHODS: In a prospective study in 161 hemodialysis patients we tested the prognostic value of changes in LVM on survival and incident cardiovascular events. Echocardiography was performed twice, 18 +/- 2 SD months apart. Changes in LVM occurring between the first and the second echocardiographic study were then used to predict mortality and cardiovascular events during the ensuing 29 +/- 13 months. The prognostic value of LVM changes was tested in a multivariate Cox's model with LVM index (LVMI) [expressed as LVM/height(2.71)], included as a covariate to control for regression to the mean. RESULTS: The rate of increase of LVMI was significantly (P= 0.029) higher in patients with incident cardiovascular events than in those without such events. Accordingly, cardiovascular event-free survival in patients with changes in LVMI below the 25th percentile was significantly (P= 0.004) higher than in those with changes above the 75th percentile. In a multiple Cox regression analysis, including age, diabetes, smoking, homocysteine, 1 g/m(2.7)/month increase in LVMI was associated with a 62% increase in the incident risk of fatal and nonfatal cardiovascular events [hazard ratio 1.62 (95% CI 1.13-2.33), P= 0.009]. CONCLUSION: Changes in LVMI have an independent prognostic value for cardiovascular events and provide scientific support to the use of repeated echocardiographic studies for monitoring cardiovascular risk in dialysis patients.     

Peritoneal T cell responses can be polarized toward Th1 or Th2 in children on chronic peritoneal dialysis

Peritoneal T cell responses can be polarized toward Th1 or Th2 in children on chronic peritoneal dialysis. Previous studies on the peritoneal immune system described the presence of activated T lymphocytes in peritoneal effluents from subjects on chronic peritoneal dialysis (CPD). Since Th1/Th2 polarized response can influence the outcome of specific infectious diseases, we investigated if activated Th1/Th2 cells can be detected in peritoneal effluents during peritoneal dialysis, in order to better understand the role of T cells in the mechanisms of peritoneal defense. We have studied 8 children (4 males, 4 females, mean age 5.8 +/- 5.7 years, range 0.3-13.4) on CPD. Peritoneal cells have been isolated from peritoneal effluents by centrifugation. Immunofluorescent staining of intracellular cytokines for flow cytometric analysis was used to detect the percentage of T cells producing either IFN-gamma (Th1) or IL-4 (Th2). In the initial study 3 months after CPD initiation, high percentages of IFN-gamma positive peritoneal T cells (38% and 63%) were detected in two subjects; this finding is consistent with a Th1 polarization of peritoneal T cells. In another subject, high percentages of IL-4 positive T cells (31%) were detected, suggesting a Th2 polarization of peritoneal T cell response. Small amounts of either Th1 or Th2 T cells (2-4%) were also detected in the other subjects. At the 1 year follow-up, Th1 polarization persisted in one subject (18% IFN-gamma positive peritoneal T cells), in another a shift from Th1 to Th2 was observed, and in the other subject a down regulation of both T cell subsets occurred. The finding that a predominance of T cells producing either IFN-gamma or IL-4 was found in 3 out of 8 children strongly suggests that peritoneal T cell responses can be polarized toward Th1 or Th2. The decrease of Th1 and/or Th2 polarized T cells in the peritoneum of 4 out of 6 subjects (after 1 year) suggests that CPD can play an immunosuppressive role on T cell peritoneal responses. Further studies are needed in order to define whether different T helper activation patterns are associated with a higher risk of peritoneal infection or of peritoneal damage.     

Segmental vertebral motion in the assessment of neck range of motion in whiplash patients

The purpose of this study was to obtain comparative data concerning the relative contribution of segmental cervical vertebral motion to the cervical range of motion (ROM) in whiplash and healthy subjects in an effort to evaluate the usefulness of X-ray analysis in future forensic and research efforts. Each subjects neck ROM was measured with an optoelectronic system and also by X-ray measurements of the angular rotation in flexion and extension. The X-rays were examined to calculate the angular movement in the sagittal plane of each of the functional units C2–C3 to C6–C7. The chronic whiplash subjects showed reduced total neck range in all directions as compared to healthy subjects (p<0.001). There was a reduced total angular rotation from flexion to extension between these two groups (p<0.01), but no significant difference, however, between chronic whiplash subjects and controls in the percentage contribution of each of the functional units C2–C3 to C6–C7 to this rotation. This data will now allow a design of trials where healthy subjects are asked to simulate restricted neck ROM while undergoing optokinetic and X-ray evaluation of segmental vertebral motion. We will be able to determine if simulators produce a similar pattern to chronic whiplash and healthy, non-simulating subjects, and thus determine if, at least for forensic and research purposes, this technique is useful in validating reported restricted neck range.