Mayer-Rokitansky-Kuster-Hauser syndrome: US aid to diagnosis

The Mayer-Rokitansky-Kuster-Hauser syndrome is composed of vaginal atresia with other variable Müllerian duct abnormalities such as bicornuate or septated uterus. The fallopian tubes, ovaries, and broad and round ligaments are normal. Unilateral renal and skeletal anomalies are associated in 50% and 12% of cases, respectively. Patients have a normal female karyotype and normal secondary sexual development. Previously, one had to rely on radiographic contrast studies and surgical exploration for accurate definition of the reproductive tract anatomy. The authors performed ultrasound (US) examinations on 12 patients, aged 5 days to 18 years, with the Mayer-Rokitansky syndrome. US allowed correct identification of the genitourinary anomalies found in these girls, including eight cases of unilateral renal agenesis; one absent, one rudimentary, and ten duplicated or obstructed uteri; eight duplicated or obstructed vaginas; and associated complications such as endometriosis. Eight of the patients had lower abdominal pain, often cyclical in nature. The findings demonstrate that high-resolution, real-time US in conjunction with water vaginography permits the anatomy of these complex anomalies to be defined.     

Gonadotrophins inhibit the expression of insulin-like growth factor binding protein-related protein-2 mRNA in cultured human granulosa-luteal cells

Insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) have been shown to be involved in ovarian follicular growth/development and steroidogenesis. Recently, a number of low-affinity IGFBP-related proteins (IGFBP-rP) have been characterized. In this study, we investigated the expression of the gene for IGFBP-rP2 (also known as connective tissue growth factor, CTGF) in human granulosa cells in vitro and in vivo. Northern blot analysis demonstrated that IGFBP-rP2 mRNA is expressed in cultured human granulosa-luteal cells obtained from women undergoing an IVF programme. Accumulation of IGFBP-rP2 mRNA was dose-dependently down-regulated by FSH and LH after 24 h treatment (both P < 0.05) in cultured granulosa-luteal cells. The inhibitory effects of gonadotrophins were mimicked by treatment with the protein kinase A activator, (Bu)(2)cAMP. Protein kinase C inhibitor staurosporine reduced, whereas protein kinase C activator TPA (12-O-tetradecanoyl phorbol 13-acetate) increased, IGFBP-rP2 mRNA accumulation. These results suggest that the inhibitory effects of gonadotrophins on IGFBP-rP2 gene expression may involve signal transduction via both protein kinase A and C pathways. Immunohistochemical analysis revealed positive staining for IGFBP-rP2 in the granulosa and theca cells of normal human ovarian follicles. Corpus luteum and ovarian surface epithelial cells were also positively stained. Modulation of IGFBP-rP2 expression by gonadotrophic hormones may have a role in ovarian follicular development and in the ovulatory process.     

Duchenne-like muscular dystrophy in two sisters with normal karyotypes: evidence for autosomal recessive inheritance

Two sisters, products of a consanguineous marriage (with a total of 12 children) showed muscle weakness at ages 7 and 6 yrs, respectively. The symptoms progressed rapidly and the patients were confined to wheelchairs at ages of 12 and 11 yrs, respectively. They had mild facial weakness and pseudohypertrophy of the calves, but neither cardiomyopathy nor mental retardation. Serum CK activities exceeded upper normal limit by 70 to 85-fold. Muscle biopsies were compatible with muscular dystrophy. Both girls had a normal karyotype. The healthy mother had mild CK elevations in two out of three occasions, but the muscle biopsy was normal. Three out of the six unaffected sibs had mild CK elevations. The findings support the concept of severe progressive muscular dystrophy with autosomal recessive inheritance. The condition is clinically indistinguishable from Duchenne muscular dystrophy.     

A dominant gene for developmental dyslexia on chromosome 3

Developmental dyslexia is a neurofunctional disorder characterised by an unexpected difficulty in learning to read and write despite adequate intelligence, motivation, and education. Previous studies have suggested mostly quantitative susceptibility loci for dyslexia on chromosomes 1, 2, 6, and 15, but no genes have been identified yet. We studied a large pedigree, ascertained from 140 families considered, segregating pronounced dyslexia in an autosomal dominant fashion. Affected status and the subtype of dyslexia were determined by neuropsychological tests. A genome scan with 320 markers showed a novel dominant locus linked to dyslexia in the pericentromeric region of chromosome 3 with a multipoint lod score of 3.84. Nineteen out of 21 affected pedigree members shared this region identical by descent (corrected p<0.001). Previously implicated genomic regions showed no evidence for linkage. Sequencing of two positional candidate genes, 5HT1F and DRD3, did not support their role in dyslexia. The new locus on chromosome 3 is associated with deficits in all three essential components involved in the reading process, namely phonological awareness, rapid naming, and verbal short term memory.


Keywords: reading disability; linkage analysis; chromosome 3     

Two translocations of chromosome 15q associated with dyslexia

Developmental dyslexia is characterised by difficulties in learning to read. As reading is a complex cognitive process, multiple genes are expected to contribute to the pathogenesis of dyslexia. The genetics of dyslexia has been a target of molecular studies during recent years, but so far no genes have been identified. However, a locus for dyslexia on chromosome 15q21 (DYX1) has been established in previous linkage studies. We have identified two families with balanced translocations involving the 15q21-q22 region. In one family, the translocation segregates with specific dyslexia in three family members. In the other family, the translocation is associated with dyslexia in one family member. We have performed fluorescence in situ hybridisation (FISH) studies to refine the position of the putative dyslexia locus further. Our results indicate that both translocation breakpoints on 15q map within an interval of approximately 6-8 Mb between markers D15S143 and D15S1029, further supporting the presence of a locus for specific dyslexia on 15q21.


Keywords: dyslexia; reading disability; chromosome 15; translocation     

Gonadotrophins inhibit and activin induces expression of inhibin/activin beta(B) subunit mRNA in cultured human granulosa-luteal cells

During the human menstrual cycle, serum inhibin concentrations fluctuate in a cyclic fashion. To examine the regulation of inhibin/activin beta(B) subunit gene expression in ovarian granulosa-luteal cells, the levels of beta(B) subunit mRNA were determined in primary cultures of human granulosa-luteal cells treated with gonadotrophins and protein kinase modulators. Granulosa cells were obtained from women undergoing an IVF programme. The cells were enzymatically dispersed, separated from red blood cells, and maintained in culture for 5--10 days before addition of different agents. Northern blot analysis with specific oligonucleotide probes was performed to study inhibin/activin beta(B) subunit mRNA levels. Both LH and FSH reduced the accumulation of beta(B) subunit mRNA in a dose-dependent manner. The protein kinase A activator, (Bu)(2)cAMP, and the protein kinase inhibitor staurosporine also inhibited beta(B) subunit mRNA expression dose-dependently. Activin A increased dose-dependently beta(B) subunit mRNA expression. Our study suggests that activin-induced and gonadotrophin-inhibited beta(B) subunit expression in granulosa cells might be key factors in the transition from inhibin B to inhibin A dominance during the menstrual cycle.     

Effects of data preprocessing on results of the epidemiological analysis of coronary heart disease and behaviour-related risk factors

BackgroundWe carried out this study to demonstrate the effects of outcome sensitivity, participant exclusions, and covariate manipulations on results of the epidemiological analysis of coronary heart disease (CHD) and its behaviour-related risk factors.Material and methodsOur study population consisted of 1592 54-year-old men, who participated in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. We used the Cox proportional-hazards model to predict the hazard of CHD and applied different sets of outcomes concerning outcome sensitivity and data preprocessing procedures regarding participant exclusions and covariate manipulations.ResultsThe mean follow-up time was 23 years, and 730 men received the CHD diagnosis. Cox regressions based on data with no participant exclusions most often discovered statistically significant associations. Loose inclusion criteria for study participants with any CVD during the follow-up and strict exclusion criteria for participants with no CVD were best in discovering the associations between risk factors and CHD. Outcome sensitivity affected the associations, whereas the covariate type, continuous or categorical, did not.ConclusionsThis study suggests that excluding study participants who are not disease-free at baseline is probably unnecessary for epidemiological analyses. Epidemiological research reports should present results based on no data exclusions together with results based on reasoned exclusions.     

Minimally lnvasive Coronary Artery Bypass Grafting: One-Year Follow-Up

Background: Use of the minimally invasive direct coronary artery bypass grafting (MIDCAB) technique has been associated with excellent primary results, and sparing of resources has been assumed. There is, however, a limited amount of information available concerning the results of mid-term follow-up. The purpose of this study was to present 1-year follow-up results of our first 130 consecutive MIDCAB patients. Methods: MIDCAB operations, defined as no sternotomy, no cardiopulmonary bypass, and no aortic manipulation were started in our clinic in February 1996. One hundred thirty patients requiring invasive treatment of coronary artery disease who were not suitable for percutaneous transluminal angioplasty were included in this series. The main outcome measures were mortality, the need for subsequent invasive treatment, and 1-year NYHA classification. Results: There was one hospital death, but during the first-year follow-up, four additional deaths occurred and three patients were reoperated on with conventional techniques. Five percutaneous transluminal coronary angioplasties (PTCAs) had to be performed, two because of anastomosic stenosis. Additionally, cardiac- or operation-related symptoms caused a total of 27 hospital visits among 23 patients during the first-year follow-up. Angiographic left internal thoracic artery (LITA)-left anterior descending artery (LAD) patency was 97.4% (37/38) (confidence interval [CI] ranged from 86.2% to 99.9%) at 3 months. After 1 year, 86.9% (113/130) of the patients were without symptoms. A clear improvement of the follow-up results was observed to be associated with increased experience during the study period. Conclusions MIDCAB operations, after some experience, can be performed with relatively good outcome. However, special attention should be directed to determination of correct anastomosic site and to avoiding anastomosic stenosis. We also recommend extended mobilization of the ITA and use of specific stabilizers. (J Card Surg 1999;14:231–237)