Predictors of mitral annulus enlargement? A real-time three-dimensional transesophageal study.

BACKGROUND: Mitral annulus (MA) enlargement can be observed in various cardiac conditions but respective influence of left atrial (LA) and left ventricle (LV) size remained unclear. METHODS: In 120 patients who underwent a clinically indicated 3D-transesophageal-echocardiography, 30 atrial fibrillation (AF), 30 secondary mitral regurgitation (SMR), 30 primary myxomatous mitral regurgitation (PMR) and 30 mitral stenosis (MS), we evaluated the association between MA area (MA-area) and LA volume (LAvol) measured using the biplane area-length method, end-diastolic (LVEDV) and end-systolic (LVESV) volumes measured using the biplane Simpson method. MA-area was measured based on 3D datasets using QLab10. RESULTS: MA-area was correlated to LVEDV (r = 0.42, p < 0.0001), LVESV (r = 0.29, p = 0.001) but more markedly to LAvol (r = 0.62, p < 0.0001). Correlation between MA-area and LAvol was sustained in all subsets whereas MA-area was not correlated to LVEDV and LVESV in patients with SMR and with PMR (all p > 0.10). In multivariate analysis main predictors of MA-area were LAvol (p < 0.0001) and myxomatous etiology of MR (p = 0.0003) followed by LVEDV (p = 0.006) and LVESV (p = 0.02). CONCLUSION: In a population of patients with a wide range of LA/LV size related to various conditions, LA volume and myxomatous MR etiology appeared as main predictors of MA size whereas LV size had a more modest influence.

Burden of illness and costs among paediatric haemophilia patients with and without central venous access devices treated in US hospitals.

INTRODUCTION: Central venous access devices (CVADs) facilitate repeated or urgent treatments for paediatric haemophilia patients, but are associated with complications. This study examined the burden of illness, healthcare utilization and costs for CVADs in a real-world hospital setting. MATERIALS AND METHODS: This study included haemophilia patients ages ≤18 years with discharges during 2006-2014 in the US Premier Healthcare Database. Haemophilia was identified using ICD-9 diagnosis codes and CVAD exposure using billing information. After matching haemophilia patients with and without CVADs on demographic and clinical characteristics, we compared infection, thrombosis, length of stay (LOS), inflation-adjusted hospital cost (2014 $USD) and readmission outcomes using generalized estimating equation models adjusted for hospital teaching status. RESULTS: Among 4793 paediatric haemophilia patients treated at one of 548 hospitals, a total of 197 patients were identified with CVAD exposure. The matched sample included 310 haemophilia patients (155 CVAD and 155 non-CVAD). CVAD cases had greater frequencies of all-cause infections (29% vs 17%, P = .01) and thrombosis (6% vs 1%, P = .06), longer adjusted mean LOS (9.5 vs 4.7 days, P = .002), higher adjusted mean inpatient total hospitalization costs ($47200 vs $25389, P = .02) as well as more inpatient and outpatient visits at 30-, 60- and 90-days (P < .05 for all differences) compared with non-CVAD patients. CONCLUSION: Paediatric haemophilia patients with CVADs experienced greater infection rates, healthcare utilization and higher hospitalization costs compared with non-CVAD patients. The results of this study may inform further research efforts to understand the costs and benefits of novel treatment alternatives for young haemophilia patients requiring CVADs.

Early menarche and blood pressure in adulthood: systematic review and meta-analysis.

Background: It has been reported that early menarche is associated with high blood pressure and hypertension. However, some studies have failed to observe such association. We carried out a systematic review and meta-analysis on the association of early menarche with hypertension and high blood pressure in adulthood. Methods: PUBMED, SciELO, Scopus and LILACS databases were searched. Studies that evaluated the association of early menarche with hypertension or high blood pressure, among women aged 20 years or more were included. Random effects models were used to pool the estimates. Meta-regression was used to evaluate the contribution of different co-variables to heterogeneity. Results: We identified 17 studies with 18 estimates on the association of early menarche with hypertension and high blood pressure. The odds of hypertension/high blood pressure was higher among women with early menarche [pooled (OR):1.25; 95% confidence interval (CI): 1.17-1.34; P < 0.001]. In the meta-regression analysis, studies evaluating 1500 subjects or more had a higher pooled OR [1.27; 95%CI (1.19;1.36)] than those with less participants. Although funnel plots showed some asymmetry, Egger tests were not statistically significant. Therefore, it is unlikely that the observed association was to publication bias. Conclusions: Early menarche is associated with hypertension among adult woman.

Homozygous PPT1 Splice Donor Mutation in a Cane Corso Dog With Neuronal Ceroid Lipofuscinosis.

A 10-month-old spayed female Cane Corso dog was evaluated after a 2-month history of progressive blindness, ataxia, and lethargy. Neurologic examination abnormalities indicated a multifocal lesion with primarily cerebral and cerebellar signs. Clinical worsening resulted in humane euthanasia. On necropsy, there was marked astrogliosis throughout white matter tracts of the cerebrum, most prominently in the corpus callosum. In the cerebral cortex and midbrain, most neurons contained large amounts of autofluorescent storage material in the perinuclear area of the cells. Cerebellar storage material was present in the Purkinje cells, granular cell layer, and perinuclear regions of neurons in the deep nuclei. Neuronal ceroid lipofuscinosis (NCL) was diagnosed. Whole genome sequencing identified a PPT1c.124 + 1G>A splice donor mutation. This nonreference assembly allele was homozygous in the affected dog, has not previously been reported in dbSNP, and was absent from the whole genome sequences of 45 control dogs and 31 unaffected Cane Corsos. Our findings indicate a novel mutation causing the CLN1 form of NCL in a previously unreported dog breed. A canine model for CLN1 disease could provide an opportunity for therapeutic advancement, benefiting both humans and dogs with this disorder.

Immediate postoperative extubation in bilateral lung transplantation: predictive factors and outcomes.

BACKGROUND: We reviewed our experience with tracheal extubation in the operating room (E-OR) among cystic fibrosis patients requiring bilateral lung transplantation to evaluate safety and determine predictive factors of E-OR. METHODS: The charts of 89 recipients (from May 2007 to June 2013) were analysed. Patients were divided into E-OR and E-ICU (intensive care unit extubation) groups. Data are expressed as numbers (percentages) or medians [25th-75th percentiles]. RESULTS: There were 41 patients in the E-OR group (46%). Donor and recipient characteristics were similar between groups. Intraoperative complications occurred less frequently in the E-OR group, and fluid and transfusion requirements were lower. Postoperative courses were different in the E-OR group, including a lower rate of grade 3 primary graft dysfunction (0 compared with 19 patients, P<0.0001) and shorter ICU (5.0 [3.7-7.2] compared with 11.5 [7.0-15.5] days) and hospital stays (22.0 [18.0-25.5] compared with 33.0 [25.0-56.5] days, respectively; P<0.0001 for both). The 1 yr survival rates were similar: 95% in the E-OR group and 98% in the E-ICU group. A statistical model built on a development cohort of 60 randomly selected patients predicted 95% of E-OR instances in this cohort and 82% of E-OR instances in the validation cohort (28 patients). Predictive factors were complications during single-lung ventilation (second graft implantation), complications during bipulmonary ventilation (end of surgery), and the ratio of arterial partial pressure of oxygen to fractional inspired oxygen (end of surgery). CONCLUSIONS: Our protocol allowed for extubation of 46% of bilateral lung transplant patients without increased postoperative risks.

Comparison of radial forearm flap and thoracodorsal artery perforator flap donor site morbidity for reconstruction of oral and oropharyngeal defects in head and neck cancer.

INTRODUCTION: Reconstruction of the oral cavity and oropharynx after tumour resection often involves the use of free flaps, but donor site morbidity must be taken into account. The radial forearm flap, the flap most commonly used in this setting, leaves a readily visible scar on an exposed region of the body. The thoracodorsal artery perforator flap (TDAP), which possesses the same plastic qualities as the radial forearm flap, leaves a scar that is hidden in the axilla. The purpose of this study was to evaluate the cosmetic results of radial forearm and thoracodorsal artery perforator free flap donor sites. MATERIAL AND METHODS: The medical charts of all patients undergoing reconstruction by a radial forearm or thoracodorsal artery perforator free flap between January 2011 and December 2011 were retrospectively reviewed. The Patient and Observer Scar Assessment Scales and the Vancouver Scar Scale were used to evaluate the quality of the scars. RESULTS: Reconstruction was performed by radial forearm flap in 4 cases and TDAP flap in 7 cases. The PSAS score was significantly lower in the TDAP group than in the radial forearm group (P=0.03), and the OSAS score was higher in the radial forearm group (21.5 versus 14). The Vancouver Scar Scale was significantly higher for radial forearm flap scars than for TDAP scars (8 versus 2.7, P=0.005). CONCLUSION: This is the first study to compare radial forearm and thoracodorsal artery perforator free flap donor site scars. It demonstrates the minimal TDAP donor site morbidity and the high level of patient satisfaction.

Subspectacular nematodiasis caused by a novel Serpentirhabdias species in ball pythons (Python regius).

Subspectacular nematodiasis was diagnosed in three captive-bred juvenile ball pythons (Python regius) from two unrelated facilities within a 6-month period. The snakes were presented with similar lesions, including swelling of facial, periocular and oral tissues. Bilaterally, the subspectacular spaces were distended and filled with an opaque fluid, which contained nematodes and eggs. Histopathology showed nematodes throughout the periocular tissue, subspectacular space and subcutaneous tissue of the head. The nematodes from both facilities were morphologically indistinguishable and most closely resembled Serpentirhabdias species. Morphological characterization and genetic sequencing indicate this is a previously undescribed rhabdiasid nematode.

The minimally important difference in the Rhinoconjunctivitis Total Symptom Score in grass-pollen-induced allergic rhinoconjunctivitis.

BACKGROUND: The minimally important difference (MID) has been defined as the smallest improvement considered worthwhile by a patient. The MID has not been estimated for the Rhinoconjunctivitis Total Symptom Score (RTSS). METHODS: In a prospective multicentre study, patients consulting for grass-pollen-induced allergic rhinitis (AR) recorded a 15-point global rating of change scale (GRCS) score and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score on a weekly basis and the individual symptom scores comprising the RTSS on a daily basis over two consecutive weeks. The MID in the RTSS was determined with anchor-based methods (using the GRCS and the RQLQ) and a distribution-based method [based on the RTSS' standard deviation (SD)]. RESULTS: The study population comprised 806 patients (253 children, 250 adolescents and 303 adults). During the first week of the study, the mean ± SD RTSSs for these age groups were 6.5 ± 3.3, 6.8 ± 3.4 and 7.0 ± 3.4, respectively. For an improvement of 2 points in the GRCS or 0.5 points in the RQLQ score, the regression analysis yielded MIDs in the RTSS of 1.24 ± 0.17 and 1.12 ± 0.14 in children, 1.33 ± 0.14 and 1.20 ± 0.13 in adolescents and 1.13 ± 0.14 and 0.89 ± 0.12 in adults, respectively. When applying distribution-based methods, the MID ranged from 1.09 to 1.13 (based on 0.33 SDs of the first-week RTSS) and from 1.22 to 1.40 (based on 0.5 SDs of the difference in RTSSs between the first and second weeks). CONCLUSION: The MID in the RTSS was consistently estimated as 1.1-1.3 (and could conceivably be rounded to 1) in patients with grass-pollen-induced AR.

[Screening method for angle closure and angle closure glaucoma using scanning laser polarimeter GDxVCC and photodynamic gonioscopy in a darkened room. One-year outcomes of systematic peripheral iridotomy]. / Méthode de dépistage du glaucome chronique par fermeture de l'angle basée sur l'utilisation systématique du GDxVCC et de la gonioscopie photodynamique. Résultats à un an d'une iridotomie systématique.

INTRODUCTION: Angle closure glaucoma, a recognized major world health issue disproportionately affecting women and Asians, is not often considered in our European populations, normotensive subjects, myopic patients, or subjects with a deep anterior chamber. Early diagnosis is worthwhile, as laser peripheral iridotomy (LPI) is an effective one-step treatment of the causal mechanism. PATIENTS AND METHODS: We have performed a retrospective study of patients who underwent an LPI, the indication for which was based on "photodynamic" gonioscopy in a darkened room showing iridotrabecular contact in darkness. Such photodynamic gonioscopy was motivated by the presence of even minute defects in the nerve fiber layer as seen on the GDxVCC or the presence of a Van Herick sign (narrow limbal anterior chamber depth). RESULTS: One hundred and three eyes of 103 patients underwent LPI and a minimum 1-year follow-up (mean follow-up almost 2 years). Mean age was 63.7±11.8 years, and women accounted for 63.1% of cases. The vast majority (78.6%) of patients had neither glaucoma nor ocular hypertension. There were 60.1% hyperopes and 39.9% myopes. Over half (57%) had a deep or a very deep anterior chamber. After LPI, there was immediate deepening of the limbal depth of the anterior chamber in 100% of cases. The aqueous humor that flowed forward was almost always viscous-looking. After 1 year, the IOP was 1.3mm Hg±2.4 lower (P<.001) (t test). All patients who had experienced morning headaches (44% of patients) were relieved of this symptom. GDxVCC after 1 year was clearly improved in 18% of cases, slightly improved in 20%, stable in 50%, slightly worse in 11% of cases, and clearly worse in 1%. Cases treated at an earlier stage had a better improvement in GDxVCC. DISCUSSION: Our study shows frequent chronic angle closure in our European population even with deep anterior chambers. Absence of a Van Herick sign does not rule out angle closure at night. A photodynamic gonioscopy with the Goldmann three-lens mirror (to avoid unintentional indentation with the small diameter lenses in these normotensive eyes) should be performed in a darkened room. LPI is an effective one-step treatment of the underlying cause, that is particularly beneficial if performed early.

Age at menarche and risk of type 2 diabetes among African-American and white women in the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: We examined race differences in the association between age at menarche and type 2 diabetes before and after adjustment for adiposity. METHODS: We analysed baseline and 9-year follow-up data from 8,491 women (n = 2,505 African-American, mean age 53.3 years; n = 5,986 white, mean age 54.0 years) in the Atherosclerosis Risk in Communities (ARIC) study. Stratifying by race, we used logistic regression to estimate the OR for prevalent diabetes at baseline, and Cox proportional hazard models to estimate the HR for incident diabetes over follow-up according to age at menarche category (8-11, 12, 13, 14 and 15-18 years). RESULTS: Adjusting for age and centre, we found that early age at menarche (8-11 vs 13 years) was associated with diabetes for white, but not African-American women in both the prevalent (white OR 1.72, 95% CI 1.32, 2.25; African-American OR 1.13, 95% CI 0.84, 1.51; interaction p = 0.043) and incident models (white HR 1.43, 95% CI 1.08, 1.89; African-American HR 1.20, 95% CI 0.87, 1.67; interaction p = 0.527). Adjustment for adiposity and lifestyle confounders attenuated associations for prevalent (white OR 1.41, 95% CI 1.05, 1.89; African-American OR 0.94, 95% CI 0.68, 1.30; interaction p = 0.093) and incident diabetes (white HR 1.22, 95% CI 0.92, 1.63; African-American HR 1.11, 95% CI 0.80, 1.56; interaction p = 0.554). CONCLUSIONS/INTERPRETATION: Early menarche was associated with type 2 diabetes in white women, and adulthood adiposity attenuated the relationship. We did not find a similar association in African-American women. Our findings suggest that there may be race/ethnic differences in the influence of developmental factors in the aetiology of type 2 diabetes, which merit further investigation.

The Analgesia Nociception Index: a pilot study to evaluation of a new pain parameter during labor.

BACKGROUND: Objective pain assessment that is not subject to influences from either cultural or comprehension issues is desirable. Analysis of heart rate variability has been proposed as a potential method. This pilot study aimed to assess the performance of the PhysioDoloris™ analgesia monitor which calculates an Analgesia Nociception Index derived from heart rate variability. It was compared with visual analogical pain scores. METHODS: Forty-five parturients who requested epidural analgesia were recruited. Simultaneous couplets of pain scores and Analgesia Nociception Index values were recorded every 5 min regardless of the presence or absence of uterine contractions. The relationship between indices was characterized, and a cut-off value of Analgesia Nociception Index corresponding to a visual analogical score >30 (range 0-100) was used to determine the positive and negative predictive value of the Analgesia Nociception Index. RESULTS: There was a negative linear relationship between visual analogical pain scores and Analgesia Nociception Index values regardless of the presence of uterine contractions (regression coefficient ± SEM=-0.18 ± 0.032 for entire dataset). Uterine contraction significantly reduced the Analgesia Nociception Index (P<0.0001). Using a visual analogical pain score >30 to define a painful sensation, the lower 95% confidence limit for the Analgesia Nociception Index score was 49. CONCLUSION: The Analgesia Nociception Index has an inverse linear relationship with visual analogical pain scores. Further studies are necessary to confirm the results of this pilot study and to look at the influence of epidural analgesia on the Analgesia Nociception Index.

[Pneumocystis jirovecii pneumonia in non-HIV infected patients: a study of 41 cases]. / Pneumocystose pulmonaire chez des patients immunodéprimés non infectés par le VIH : étude de 41 cas.

BACKGROUND: The increasing use of immunosuppressive and cytotoxic therapies leads to a growing number of opportunistic infections especially Pneumocystis jirovecii pneumonia (PCP). The purpose of our study was to describe the population involved, and to assess clinical, biological, and mortality data. METHODS: We collected retrospectively the whole medical file of all PCP cases diagnosed in non-HIV infected patients, in two French University Hospitals in the last decade (1999-2009). Diagnosis was made on standard coloration and/or immunofluorescence analysis of bronchoalveolar lavage fluid (BAL). RESULTS: Forty-one patients were included in the study, mean age 56 (±12.5) years, sex ratio 0.71 men/woman. Underlying diseases were as follow: 12 patients (29%) were renal transplant recipients, 13 (32%) were treated for solid cancers, and 16 (39%) suffered from various diseases (three allogenic bone-marrow transplantation, 11 hematological malignancies, one pulmonary transplantation, one vasculitis). Twelve patients died (i.e. 29%). Median lymphocyte count was 542/mm(3). More than 85% patients received corticosteroids at a median cumulative 6-month dose of 2700mg. Seven patients (17%) had a PCP prophylaxis. Clinical worsening at day 5 (P<0.003), poor control of the underlying disease (P<0.015), WHO performans status superior than 2 (P<0.025), high temperature (P<0.04), and high oxygen flow (P<0.042) were linked to a poor prognosis. DISCUSSION/CONCLUSION: The prognosis factors found are mostly linked to the patients' clinical severity. We would like to highlight: first, near to 30% mortality rate, secondly, a lack of prophylaxis in 34 patients, reflecting the difficulty to define PCP's risk in non HIV-infected patients.

Pharmacokinetics and tolerability of a novel long-acting glucagon-like peptide-1 analog, CJC-1131, in healthy and diabetic subjects.

OBJECTIVE: The safety, tolerability, pharmacokinetics and preliminary pharmacodynamics of single rising doses of a novel GLP-1 analog, CJC-1131, was evaluated. METHODS: CJC-1131 was subcutaneously injected in 8 groups (1.5 - 20.5 microg/kg) of healthy subjects (each group of six subjects included 1 placebo per dose level). CJC-1131 was also injected subcutaneously in 6 groups (1.5 - 12 microg/kg) of Type 2 diabetic patients after a 9-day washout period from their own anti-diabetic medication. Each group of 8 patients included 2 placebo-treated patients. Seven blood glucose measurements were taken daily, and meal tolerance tests were performed on the day before dosing and on Day 3. RESULTS: CJC-1131 was quickly absorbed from the subcutaneous space, and a less than dose-proportional increase was found in Cmax. The half-life of CJC-1131 varied from 8.9 - 14.7 days in healthy subjects and from 9.1 - 13.8 days in patients. The maximum tolerated dose in healthy subjects was established at 12 microg/kg with nausea and vomiting being the dose-limiting events. These events occurred generally in the morning after dosing. Blood glucose levels in patients decreased on Day 1 in proportion with dose, with a maximum average decrease of 4.1 mmol/l in the highest dose group. Higher doses appeared to be related to a slight weight loss in patients. CONCLUSIONS: Conjugation to albumin led to a major prolongation of the half-life of GLP-1. The tolerability of this potential antidiabetic drug seems to be limited only by gastrointestinal complaints.

Systematic salpingoscopy and microsalpingoscopy during fertiloscopy.

STUDY OBJECTIVE: To assess the feasibility of routine salpingoscopy and microsalpingoscopy by the vaginal route during fertiloscopy. DESIGN: Retrospective continuous series (Canadian Task Force classification II-2). SETTING: Private reproductive center. PATIENTS: Five hundred infertile women with no obvious pathology. INTERVENTIONS; Fertiloscopy with salpingoscopy followed by microsalpingoscopy. MEASUREMENTS AND MAIN RESULTS: Salpingoscopy was possible in 85% of women. In those with no pathology, only 8.2% had abnormal salpingoscopy but 37% had abnormal microsalpingoscopy. CONCLUSION: Fertiloscopy allows salpingoscopy and microsalpingoscopy to be performed in a reproducible and simple manner. Thus intratubal exploration should be integral to infertility assessment.

[Psychological profile of patients with COPD: contribution of Semiometry]. / Profil psychologique des malades porteurs de BPCO. Apport de la Sémiométrie.

Patients with chronic bronchitis often ignore, or pretend to ignore, their disease and generally consult very late. The physician's advice is often quite vague and centered on smoking. One of the objectives of this study was to better understand the psychological profile of patients with chronic bronchitis in order to better apprehend the patient-physician relationship and therapeutic options. Semiometry was designed to overcome the problem encountered by physicians who would like to understand who their patients are without directly asking them. The concept is based on submitting very ordinary words to these subjects and asking them whether they like the word or not. An analysis of their responses allows a very deep understanding of their psychological profile. Briefly, the patient-physician relationship is quite difficult in COPD. The patient "brings" the disease to the physician, "putting" it in his hands and asking him to cure it without having to do anything concerning himself, his life or his behavior. The physician is called on to answer this challenge that can be expressed as "trying to get the patient to play the game without getting caught".

Identification of high molecular weight serine-proteases in Loxosceles intermedia (brown spider) venom.

High molecular weight serine-proteases have been identified in Loxosceles intermedia (brown spider) venom. The mechanism by which Loxosceles spp venoms cause dermonecrotic injury (a hallmark of loxoscelism) is currently under investigation, but it seems to be molecularly complex and in some instance proteases might be expected to play a role in this skin lesion. In the present investigation, when we submitted L. intermedia venom to linear gradient 3-20% SDS-PAGE stained by a monochromatic silver method we detected a heterogeneous protein profile in molecular weight, ranging from 850- to 5-kDa. In an attempt to detect zymogen molecules of proteolytic enzymes, venom aliquots were treated with several exogenous proteases. Among them, trypsin activated two gelatinolytic molecules of 85- and 95-kDa in the venom. In experiments of hydrolysis inactivation using different protease inhibitors for four major class of proteases, we detected that only serine-type protease inhibitors were able to inactivate the 85- and 95-kDa enzymes in the venom. An examination of the 85- and 95-kDa gelatinolytic activities as a function of pH showed that these proteases had no apparent activities at pH below 5.0 and higher than 9.0 and displayed little activity at pH 6.0. with the optimal pH for their activities ranging from 7.0 to 8.0. Evaluation of the functional specificities of the 85- and 95-kDa venom proteases showed that these proteases efficiently degrade gelatin (denatured collagen) but have no proteolytic activity on hemoglobin, immunoglobulin, albumin, librinogen or laminin, suggesting specificity of their proteolytic actions. We describe here two serine-proteases activities in L. intermedia venom probably involved in the harmful effects of the venom.

Prevalence of insomnia in a survey of 12,778 adults in France.

This study was an epidemiological questionnaire survey of a representative sample of the French population that included 12 778 individuals and in which adapted DSM-IV criteria for the definition of insomnia were used. Our goals were not only to assess the prevalence of 'insomnia' using these criteria, but also to compare the results obtained with those of prior studies using different definitions of 'insomnia'. The aim of this study was also to identify where areas of agreement and disagreement existed, as we believe that it is important to emphasize these points because DSM-IV recommendations are supposedly reflected in clinical practice. Seventy-three per cent of the individuals surveyed complained of a nocturnal sleep problem, but only 29% reported at least one sleep problem three times per week for a month, and 19% (2428 subjects) had at least one sleep problem three times per week for a month and complained of daytime consequences (DSM-IV criteria). Only 9% had two or more nocturnal sleep problems with daytime consequences and were classified as 'severe insomniacs'. Our study indicates that if DSM-IV criteria are used, the diagnosis of 'insomnia' is lower than in other epidemiological studies. The DSM criteria have an advantage in that they emphasize the daytime consequences of nocturnal sleep disturbances, which seem to be responsible for the most important socio-economic costs of the problem.

Phenotypic characteristics of early-onset autosomal-dominant type 2 diabetes unlinked to known maturity-onset diabetes of the young (MODY) genes.

OBJECTIVE: To investigate whether there are forms of early-onset autosomal-dominant type 2 diabetes that are distinct from typical maturity-onset diabetes of the young (MODY) and to characterize their phenotypic characteristics. RESEARCH DESIGN AND METHODS: The study included 220 affected subjects from 29 families in which early-onset type 2 diabetes occurred in multiple generations and was not linked to known MODY genes (MODY gene-negative families). All individuals underwent an oral glucose tolerance test and other clinical measurements aimed at investigating the underlying metabolic defect and the presence of diabetic complications. For comparison, 79 affected carriers of MODY3 (hepatocyte nuclear factor [HNF]-1 alpha) mutations were similarly examined. RESULTS: Subjects from MODY gene-negative pedigrees were diagnosed with diabetes at an older age (36 +/- 17 vs. 21 +/- 10 years, P = 0.0001) and were more frequently obese (52 vs. 18%, P = 0.0001) than MODY3 individuals. MODY gene-negative patients who were insulin treated required more exogenous insulin than did MODY3 subjects (0.7 +/- 0.4 vs. 0.45 +/- 0.2 U.kg-1.day-1, P = 0.04), despite similar C-peptide levels. Among subjects not treated with insulin, MODY gene-negative subjects had significantly higher serum insulin levels, both fasting (16.5 +/- 15 vs. 6.5 +/- 5 microU/ml, P = 0.027) and 2 h after a glucose load (53 +/- 44 vs. 11 +/- 10, P = 0.002). They also had higher serum triglycerides (P = 0.02), higher cholesterol levels (P = 0.02), more hypertension (P = 0.0001), and more nephropathy (P = 0.001). Differences persisted when families were matched for age at diagnosis. CONCLUSIONS: Our findings indicate the existence of forms of early-onset autosomal-dominant type 2 diabetes that are distinct from MODY and are frequently characterized by insulin resistance, similar to later-onset type 2 diabetes. Because of the Mendelian pattern of inheritance, the goal of identifying the genes involved in these forms of diabetes appears to be particularly feasible.

Evaluation of the performance of fertiloscopy in 160 consecutive infertile patients with no obvious pathology.

We have defined fertiloscopy as the combination in one investigation of transvaginal hydropelviscopy, dye-test, optional salpingoscopy, and hysteroscopy, performed on an outpatient basis under local anaesthesia or neuroleptanalgesia. We have applied this approach in a routine manner to 160 infertile patients with no obvious pathology. Fertiloscopy was achieved in 154 patients (96.2%). In five patients visualization was not satisfactory because of technical problem or adhesions in the pouch of Douglas. We had one (0.6%) rectal injury, which was treated conservatively. Sixty patients (37.5%) had normal fertiloscopic examination. Endometriosis was discovered in 21 patients (13.1%) post-pelvic inflammatory disease (PID) lesions in 58 cases (36.2%), and subtle abnormalities in 15 cases (9.3%). Salpingoscopy was completed when post-PID lesions were encountered. In 39% of cases only partial examination was possible because of external tubal adhesions, but it was nevertheless sufficient to obtain a good view of the first one-third of the ampulla. In all, 74 patients (46.2%) were referred directly to in-vitro fertilization (IVF) procedures, and so avoided a further laparoscopy. Quality of imaging, accuracy of the pelvic examination in a physiological manner, and safety of the procedure are the main advantages of this minimally invasive technique. Selection of the patients for surgery is therefore enhanced, and indication for IVF is better balanced, avoiding the performance of extensive procedures in patients who should thus benefit from this less traumatic alternative.

HB-GAM/pleiotrophin but not RIHB/midkine enhances chondrogenesis in micromass culture.

The heparin-binding growth-associated molecule HB-GAM (also named pleiotrophin) and the retinoic acid-induced heparin-binding protein RIHB (chicken midkine) are developmentally regulated proteins forming a new family of heparin-binding molecules with putative functions during cell growth and differentiation. A direct involvement of these molecules during chondrogenesis in vivo was suggested by their patterns of expression. The putative chondrogenic activity of these molecules was investigated in vitro using micromass cultures from chicken limb bud mesenchymal cells. Exogenous HB-GAM, not RIHB, was found to enhance chondrogenesis in this system. These results provide a strong incentive for considering and further investigating the role of this protein in the control of limb cartilage differentiation.