Linkage mapping of a nonspecific form of X‐linked mental retardation (MRX53) in a large Pakistani family

Nonspecific X‐linked mental retardation is a nonprogressive, genetically heterogeneous condition that affects cognitive function in the absence of other distinctive clinical manifestations. We report here linkage data on a large Pakistani family affected by a form of X‐linked nonspecific mental retardation. X chromosome genotyping of family members and linkage analysis allowed the identification of a new disease locus, MRX53. The defined critical region spans approximately 15 cM between DXS1210 and DXS1047 in Xq22.2–26. A LOD score value of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081. © 2001 Wiley‐Liss, Inc.     

Prospective validation of P2/MS noninvasive index using complete blood counts for detecting oesophageal varices in B‐viral cirrhosis

Backgrounds: Periodic endoscopic screening for oesophageal varices (OVs) and prophylactic treatment for high‐risk OVs (HOVs; medium/large OVs or small OVs plus red sign/decompensation) are currently recommended for all cirrhotic patients. However, if a simple, noninvasive test is available, many low‐risk patients may reliably avoid endoscopy. Aims: We conducted a large‐scale validation study of a simple, noninvasive test called P2/MS based on complete blood counts, (platelet count)²/[monocyte fraction (%) × segmented neutrophil fraction (%)], and compared it with other predictive tests for HOVs in B‐viral cirrhotic patients. Methods: From 2008 to 2009, we prospectively enrolled 318 consecutive B‐viral cirrhotic patients. All underwent endoscopy and laboratory evaluation. Results: An area under the receiver operating characteristic curve of P2/MS was 0.941 for HOVs, comparable with those of the age–spleen platelet ratio index (0.922, P=0.317) and spleen–platelet ratio index (0.922, P=0.324), and better than those of age–platelet index (0.653, P<0.001), aspartate aminotransferase (AST)–platelet ratio index (0.871, P<0.006) and AST‐alanine aminotransferase ratio (0.644, P<0.001). P2/MS<11 reliably identified 83 patients as having HOVs (94.0% positive predictive value), while at a cutoff of 25 and 179 as not having HOVs (94.4% negative predictive value). Overall, P2/MS reliably determined the likelihood of HOVs in 262 patients (82.4%). These cutoffs were validated internally using bootstrap resampling methods, which showed good agreement. Conclusions: P2/MS is a simple, accurate and economical method, reducing the need for endoscopy in B‐viral cirrhosis. Patients with P2/MS<11 should be considered for appropriate prophylactic treatments, while those with P2/MS>25 may avoid endoscopy reliably.     

Effects of 1‐O‐hexyl‐2,3,5‐trimethylhydroquinone on carbon tetrachloride‐induced hepatic cirrhosis in rats

Aim: The present study was undertaken to evaluate the effects of 1‐O‐hexyl‐2,3,5‐trimethylhydroquinone (HTHQ), a synthesized vitamin E derivative, on carbon tetrachloride (CCl₄)‐induced cirrhosis. Methods: Rats were treated with hypodermic injections of CCl₄ twice a week to induce the hepatic cirrhosis, and given drinking water containing HTHQ or solvent. Primary cultures of rat hepatocytes were performed to evaluate the effects of HTHQ on the expression of inducible nitric oxide synthase (iNOS). Results: Masson's staining of rat livers showed fibrosis around pseudo‐lobules in the CCl₄ group, the lesions being reduced in the CCl₄ HTHQ group. Increases in liver tissue hydroxyproline and α₁(I) collagen, α‐smooth muscle actin and iNOS induced by CCl₄, were also markedly diminished by HTHQ. Furthermore, both HTHQ and vitamin E attenuated interleukin‐1β‐induced iNOS protein expression in cultured hepatocytes, the potency of HTHQ being 10‐times higher than that of vitamin E. Conclusion: HTHQ may inhibit development of hepatic cirrhosis in rats, more potently than vitamin E, by inhibiting the iNOS expression in hepatocytes. Because vitamin E has a radical scavenging action, roles of NO and peroxynitrite will be discussed in the effects of HTHQ on the fibrosis.     

Case–control studies on risk factors for chronic obstructive pulmonary disease: how does the sampling of the cases and controls affect the results?

Introduction: Sampling is regarded as crucial to the validity of case–control studies. Ideally, cases and controls should be selected from the same source population, but deviations from this approach are often seen. Objective: Our objective was to examine how exposure–disease relationships in a study on chronic obstructive pulmonary disease (COPD) were affected by the sampling sources of cases and controls. Methods: A Norwegian case–control study on COPD including 1909 subjects used three sources of recruitment for cases (general population, hospital registry and volunteers) and two sources for controls (general population and volunteers). This resulted in six sampling combinations of cases and controls (groups A–F). We examined how the risk factors gender, age, smoking, educational level and comorbidity were associated with COPD in these six sampling groups. Results: Several exposure–disease associations were dependent on variation in sampling source, thereby demonstrating the possibility of selection bias. The theoretically most ideal sampling group is likely group A, where both cases and controls are recruited from a general population. When using group A as a reference, the groups containing either voluntary controls and/or hospital‐based cases deviated the most, suggesting higher susceptibility to selection bias in these groups. Conclusion: Recruitment from several sources made our study design vulnerable to selection bias. Our findings should bring about increased awareness to the sampling process, and encourage sampling of cases and controls from the same source population in future studies. Please cite this paper as: Sørheim I‐C, Johannessen A, Grydeland TB, Omenaas ER, Gulsvik A and Bakke PS. Case–control studies on risk factors for COPD: how does the sampling of the cases and controls affect the results? The Clinical Respiratory Journal 2010; 4: 89–96.     

Female sexual receptivity is defective in juvenile hormone-deficient mutants of theapterous gene ofDrosophila melanogaster

During reproductive maturation of female insects, the acquisition of sexual receptivity is coordinated with ovarian development. Juvenile homone regulates vitellogenesis in the ovaries, but the action of this hormone in the development of sexual behavior is less well-understood. A strain ofDrosophila melanogaster carrying a mutation in theapterous gene(ap ⁴) was known to exhibit arrested vitellogenesis (rescuable by applying exogenous juvenile hormone), sterility of both sexes, and a deficiency of juvenile hormone. In this study, we examined the effects of mutations ofap on female receptivity and its relationship to juvenile hormone. We observed abnormally low female receptivity in homozygousap strains, and heteroallelic combinations ofap mutations exhibited low receptivity. For female receptivity,ap showed no dominance (i.e.,ap/ap ⁺ was intermediate betweenap/ap andap ⁺/ap ⁺). Low receptivity mapped genetically to theap locus. The reduction in female receptivity in these mutants is positively correlated with levels of juvenile hormone synthesized by their corpora allata.This work was supported in part by The Scheinfeld Center for Humans Genetics in the Social Sciences (J.R.), The National Science Foundation (BNS-882 1339 to J.R.), BARD (No. IS-1664-89R to D.S.), The Israel Cancer Research Fund (grant to D.S.), The Rekanati Foundation of Tel Aviv University (grant to D.S.), and The Israeli Fruit Council (award to M.A.)     

Improvement of respiratory compromise through abductor reinnervation and pacing in a patient with bilateral vocal fold impairment

Objectives/Hypothesis.

To determine whether respiratory compromise from bilateral vocal fold impairment (paralysis) can be objectively alleviated by reinnervation and pacing.

Methods.

A patient with paramedian vocal folds and synkinesis had a tracheotomy for stridor after bilateral laryngeal nerve injury and Miller Fisher syndrome. One posterior cricoarytenoideus (PCA) received a nerve‐muscle pedicle fitted with a perineural electrode for pacemaker stimulation. The airway was evaluated endoscopically and by spirometry for up to 1 year.

Results.

Bilateral vocal fold patency during quiet breathing was reversed to active vocal fold adduction during tracheal occlusion. Peak inspiratory flows (PIFs) were significantly higher (P < .001) after reinnervation. PIFs and glottic apertures increased further under stimulation (42 Hz, 1–4 mA, 42–400 μsec). although the differences were not significant.

Conclusions.

Based on our preliminary data, PCA reinnervation and pacing offer promise for amelioration of respiratory compromise after paradoxical adduction in bilateral vocal fold impairment. Laryngoscope, 2010     

Potential application of ocular and cervical vestibular‐evoked myogenic potentials in meniere's disease: A review

By stimulating the ear with air‐conducted sound or bone‐conducted vibration stimuli, vestibular‐evoked myogenic potential (VEMP) can be recorded on the contracted neck muscles, termed cervical VEMP (cVEMP), and on the extraocular muscles, termed ocular VEMP (oVEMP). These two electrophysiological tests expand the test battery for clinicians to explore the dynamic otolithic function, adding a potential usefulness to the sacculocollic reflex and vestibulo‐ocular reflex, respectively. The inner ear test battery, including audiometry, and cVEMP, oVEMP and caloric tests, is designed for complete evaluation of the inner ear function, namely, the cochlea, saccule, utricle, and semicircular canals, respectively. Using this test battery to study the localization and prevalence of hydrops formation reveals that the declining function in the cochlea, saccule, utricle, and semicircular canals mimics the declining sequence of hydrops formation in temporal bone studies. This study reviewed the physiological results in Meniere's patients via the inner ear test battery, especially the potential application of the oVEMP and cVEMP tests, to correlate with the histopathological findings of Meniere's disease. Laryngoscope, 2012     

The Basement Membrane and the Sex Establishment in the Juvenile Hermaphroditism During Gonadal Differentiation of the Gymnocorymbus ternetzi (Teleostei: Characiformes: Characidae)

Although there are several studies on morphogenesis in Teleostei, until now there is no research describing the role of the basement membrane in the establishment of the germinal epithelium during gonadal differentiation in Characiformes. In attempt to study these events that result in the formation of ovarian and testicular structures, gonads of Gymnocorymbus ternetzi were prepared for light microscopy. During gonadal development in G. ternetzi, all individuals first developed ovarian tissue. The undifferentiated gonad was formed by somatic cells (SC) and primordial germ cells (PGCs). After successive mitosis, the PGCs became oogonia, which entered into meiosis originating oocytes. An interstitial tissue developed. In half of the individuals, presumptive female, prefollicle cells synthesized a basement membrane around oocyte forming a follicle. Along the ventral region of the ovary, the tissue invaginated to form the ovigerous lamellae, bordered by the germinal epithelium. Stroma developed and the follicle complexes were formed. The gonadal aromatase was detected in interstitial cells in the early steps of the gonadal differentiation in both sexes. In another half of the individuals, presumptive male, there was no synthesis of basement membrane. The interstitium was invaded by numerous granulocytes. Pre‐Leydig cells proliferated. Apoptotic oocytes were observed and afterward degenerated. Spermatogonia appeared near the degenerating oocytes and associated to SCs, forming testicular tubules. Germinal epithelium developed and the basement membrane was synthesized. Concomitantly, there was decrease of the gonadal aromatase and increase in the 3β‐HSD enzyme expression. Thus, the testis was organized on an ovary previously developed, constituting an indirect gonochoristic differentiation. Anat Rec, 298:1984–2010, 2015. © 2015 Wiley Periodicals, Inc.