Diastolic function in children and adolescents on dialysis and after kidney transplantation: an echocardiographic assessment

Thirty-seven children and adolescents on renal replacement therapy (11 on haemodialysis, 14 on continuous ambulatory peritoneal dialysis and 12 after renal transplantation) were studied by echocardiography, echo-Doppler and phonocardiography. Right and left ventricular (R/L V) diastolic functions were measured by transmitral and transtricuspid flow velocities and by LV isovolumic relaxation time (LVIRT). Thirty-seven age- and sex-matched healthy subjects served as controls. R/L V diastolic dysfunction was only observed in the dialysis patients. In these patients LVIRT was prolonged. LV and RV peak inflow velocities were increased both in early (E) and late (A) diastole with a reduction in the E/A ratios. This pattern of diastolic dysfunction is compatible with the combined effects of a hypercirculatory state (volume overload, anaemia, arteriovenous fistula) and an abnormality of cardiac relaxation. The transplant patients showed no major cardiac abnormalities.     

Dog bites in urban children

As a result of a perceived increase in pit bull injuries, all children who presented to The Children's Hospital of Philadelphia during 1989 for evaluation of dog bite injuries were prospectively studied. Epidemiologic information was collected from parents, either at the time of visit or by phone on the following day. A total of 168 children were enrolled; the mean age was 8 years. Males outnumbered females 1.5:1. Most (61%) injuries occurred in or around the home and involved dogs known to the patient (77%). Types of injuries included abrasions (33%), punctures (29%), and lacerations (38%). Thirteen bites had associated complications; nine developed infection. Twelve (7%) children required admission to the hospital. More than 12 different purebreeds or cross-breeds were identified as perpetrators, including German shepherds (n = 35), pit bulls (n = 33), rottweilers (n = 9), and Dobermans (n = 7). Most (54%) animals were contained (ie, leashed, fenced, in-house) at the time of injury. Fewer (46%) were provoked prior to biting. Significantly more pit bull injuries (94% vs 43%, P less than .001) were the consequence of unprovoked attacks and involved freely roaming animals (67% vs 41%, P less than .01). Children aged 5 or younger were more likely to provoke animals prior to injury than were older children (69% vs 36%, P less than .001). It is recommended that families with young children be the target of pet safety education and that measures be sought that would lead to early identification of a potentially dangerous dog and restrict ownership.     

Inositol 6 g daily may be effective in depression but not in schizophrenia

Inositol is an important precursor for second messenger synthesis and has been reported to be reduced by lithium treatment in rat brain and in human CSF in depression. An open trial of 6 g/day in 11 depressed patients resistant to previous treatment led to major improvement in nine patients. The enzyme synthesizing inositol has been reported to be elevated in schizophrenia, suggesting an attempted compensation for possible inositol deficiency. A controlled double-blind crossover trial in 10 chronic schizophrenic patients of 6 g/day of inositol for 30 days did not reveal any benefit.     

Evidence for the Presence of Insulin-Dependent Diabetes-Associated Alleles on the Distal Part of Mouse Chromosome 6

Type 1 diabetes (IDDM) is a complex disorder with multifactorial and polygenic etiology. A genome-wide screen performed in a BC1 cohort of a cross between the nonobese diabetic (NOD) mouse with the diabetes-resistant feral strain PWK detected a major locus contributing to diabetes development on the distal part of chromosome 6. Unlike the majority of other Idd loci identified in intraspecific crosses, susceptibility is associated with the presence of the PWK allele. Genetic linkage analysis of congenic lines segregating PWK chromosome 6 segments in a NOD background confirmed the presence of the Idd locus within this region. The genetic interval defined by analysis of congenic animals showed a peak of significant linkage (P=0.0005) centered on an ~9-cM region lying between D6Mit11 and D6Mit25 genetic markers within distal mouse chromosome 6.     

A-raf oncogene localizes on mouse X chromosome to region some 10–17 centimorgans proximal to hypoxanthine phosphoribosyltransferase gene

The localization of the A-rafcellular oncogene on the mouse X chromosome has been determined using Xbal-restricted DNAs prepared from progeny of an interspecies backcross between the B6.CBA.R1 and the Spe/Pas mouse strains. This localization to the proximal part of the mouse X chromosome has been confirmed by the use of somatic cell hybrids, carrying partially deleted X chromosomes and suggests that the A-raf oncogene localizes to a region lying some 10–17 centimorgans proximal to the hypoxanthine phosphoribosyltransferase (Hprt) gene between the locus DXPas4and the locus DXPas7defined by the cross-reacting human X chromosome-specific probe DXS32 (M2C). This localization on the mouse X chromosome is compatible with the presence of the A-rafoncogene on the short arm of the human X chromosome between the centromere and Xp21.     

Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development

FOXL2 mutations cause gonadal dysgenesis or premature ovarian failure (POF) in women, as well as eyelid/forehead dysmorphology in both sexes (the 'blepharophimosis-ptosis-epicanthus inversus syndrome', BPES). Here we report that mice lacking Foxl2 recapitulate relevant features of human BPES: males and females are small and show distinctive craniofacial morphology with upper eyelids absent. Furthermore, in mice as in humans, sterility is confined to females. Features of Foxl2 null animals point toward a new mechanism of POF, with all major somatic cell lineages failing to develop around growing oocytes from the time of primordial follicle formation. Foxl2 disruption thus provides a model for histogenesis and reproductive competence of the ovary.     

Localisation of X linked recessive idiopathic hypoparathyroidism to a 1.5 Mb region on Xq26-q27.

X linked recessive idiopathic hypoparathyroidism (HPT) has been observed in two kindreds from Missouri, USA. Affected subjects, who are males, suffer from infantile onset of epilepsy and hypocalcaemia, which appears to be the result of an isolated congenital defect of parathyroid gland development; females are not affected and are normocalcaemic. The gene causing HPT has been previously mapped to a 7 cM interval, flanked centromerically by F9 and telomerically by DXS98, in Xq26-q27, and an analysis of mitochondrial DNA has established a common ancestry for these two kindreds. In order to define further the map location of HPT and thereby facilitate its isolation, we have undertaken linkage studies using polymorphic loci whose order has been established as Xcen - DXS1001 - DXS294 - DXS102 - F9 - DXS1232 - DXS984 - CDR1 - DXS105 - DXS1205 - DXS1227 - DXS98 - DXS52 - Xqter, within this region. Our results established linkage (lod score > 3) between HPT and eight of these 12 loci and indicated that the most likely location of HPT was within a 1.5 Mb interval flanked centromerically by F9 and telomerically by DXS984. Thus, the results of this study have helped to refine the map location of HPT, and this will facilitate the identification of this putative developmental gene and its role in the embryological formation of the parathyroids.