A locus for autosomal dominant anterior polar cataract on chromosome 17p

Inherited cataract is a clinically and genetically heterogeneous disease. Here we report the identification of a new locus for an autosomal dominant anterior polar cataract on the short arm of chromosome 17. To map this new locus we performed genetic linkage analysis with microsatellite markers in a four-generation pedigree. After exclusion of seven candidate loci for cataract, we obtained significant positive LOD scores for markers D17S849 (Z = 4.01 / theta = 0.05) and D17S796 (Z = 4.17 / theta = 0.05). Multipoint analysis gave a maximum LOD score of 5.2 (theta max = 0.06) between these two markers. From haplotype analysis, the cataract locus lies in the 13 cM interval between markers D17S849 and D17S796. This study provides the first genetic mapping of an autosomal dominant anterior polar cataract.      

<Emphasis Type="Italic">TCF7L2</Emphasis>variant genotypes and type 2 diabetes risk in Brazil: significant association,but not a significant tool for risk stratification in the general population

Background  

Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population.     

Type 2 diabetes,polycystic ovary syndrome and the insulin resistance syndrome in adolescents: Are they one big iceberg?

Obesity in children may cause overt clinical disease in childhood. The complex endocrine and metabolic changes of obesity and insulin resistance in adolescents result in hyperinsulinemia, dyslipidemia, hypertension, steatohepatitis, glucose intolerance, type 2 diabetes, acanthosis nigricans and ovarian hyperandrogenemia, commonly known as polycystic ovarian syndrome (PCOS). Type 2 diabetes and PCOS in adolescents are new endocrine diseases in this age group that require unique approaches to diagnosis and treatment. The direct correlation between duration of disease and control of the disease, and subsequent long term complications of these two diseases, predict serious morbidity in young adult life for the affected adolescents. Pediatricians have an important role in the prevention, diagnosis and treatment of obesity, insulin resistance syndrome, type 2 diabetes and PCOS.     

原发性免疫性血小板减少症的研究和诊治:国际共识报告

(接上期472页)达那唑:是一种作用较弱的雄激素,口服剂量为每次200mg,每天2～4次(每天10～15 mg/kg).57例脾切除术后的ITP患者中,反应率为60%～67%(血小板＞50×109/L,持续2个月以上).老年女性和脾切后的患者效果最好.氨苯砜:是一种中等强度的肾上腺皮质激素类药物,常以每次75～100 mg、每天1次口服.对一线肾上腺皮质激素治疗无反应的患者,氨苯砜可使脾切除术推迟32个月以上(证据水平Ⅱb).然而,脾切除术后患者对该药的反应率较低.     

The Influence of Two Different Invitation Letters on Chlamydia Testing Participation: Randomized Controlled Trial

Background

In the Netherlands, screening for chlamydia (the most prevalent sexually transmitted infection worldwide) is a relatively simple and free procedure. Via an invitation letter sent by the public health services (PHS), people are asked to visit a website to request a test kit. They can then do a chlamydia test at home, send it anonymously to a laboratory, and, within two weeks, they can review their test results online and be treated by their general practitioner or the PHS. Unfortunately, the participation rates are low and the process is believed to be not (cost-) effective.

Objective

The objective of this study was to assess whether the low participation rate of screening for chlamydia at home, via an invitation letter asking to visit a website and request a test kit, could be improved by optimizing the invitation letter through systematically applied behavior change theories and evidence.

Methods

The original letter and a revised letter were randomly sent out to 13,551 citizens, 16 to 29 years old, in a Dutch municipality. Using behavior change theories, the revised letter sought to increase motivation to conduct chlamydia screening tests. The revised letter was tailored to beliefs that were found in earlier studies: risk perception, advantages and disadvantages (attitude), moral norm, social influence, and response- and self-efficacy. Revisions to the new letter also sought to avoid possible unwanted resistance caused when people feel pressured, and included prompts to trigger the desired behavior.

Results

No significant differences in test package requests were found between the two letters. There were also no differences between the original and revised letters in the rates of returned tests (11.80%, 581/4922 vs 11.07%, 549/4961) or positive test results (4.8%, 23/484 vs 4.1%, 19/460). It is evident that the new letter did not improve participation compared to the original letter.

Conclusions

It is clear that the approach of inviting the target population through a letter does not lead to higher participation rates for chlamydia screening. Other approaches have to be developed and pilot tested.     

Viability of partially damaged human embryos after cryopreservation

In our centre, embryos are judged to have survived cryopreservation if at least half of the initial number of blastomeres remain intact. Therefore both fully intact and partially damaged embryos are transferred. The aim of this study was to investigate the viability of partially damaged human embryos after cryopreservation. We retrospectively analysed the implantation and in-vivo development of embryos which were either fully intact or had lost some blastomeres after cryopreservation. Oocytes were collected following stimulation with the gonadotrophin-releasing hormone (GnRH)-agonist Buserelin and human menopausal gonadotrophin. Supernumerary multicellular embryos with not more than 20% of their volume filled with anucleate fragments were frozen on day 2 or day 3 of the cycle using a slow cooling procedure with dimethylsulphoxide as the cryoprotectant. Following slow thawing, 431 fully intact embryos were transferred in 314 embryo transfer procedures and 488 partially damaged embryos were transferred in 327 such procedures. The percentage of gestational sacs with fetal heartbeat obtained after transfer of fully intact embryos was almost three times higher than that after transfer of partially damaged embryos (11.4 versus 3.5%). Forty-five children (birth rate 10% per embryo transfer) were born after transfer of fully intact embryos and 14 after transfer of embryos from which some blastomeres had been lost following cryopreservation. In conclusion, although children have been delivered after transfer of partially damaged embryos, the aim of a cryopreservation programme must be to obtain fully intact embryos after thawing.      

The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis

Tuberous sclerosis is an autosomal dominant trait in which the dysregulation of cellular proliferation and differentiation results in the development of hamartomatous growths in many organs. The TSC2 gene is one of two genes determining tuberous sclerosis. Inactivating germline mutations of TSC2 in patients with tuberous sclerosis and somatic loss of heterozygosity at the TSC2 locus in the associated hamartomas indicate that TSC2 functions as a tumour suppressor gene and that loss of function is critical to expression of the tuberous sclerosis phenotype. The TSC2 product, tuberin, has a region of homology with the GTPase activating protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in vitro. Here we show that the region of homology between tuberin and human rap1GAP and the murine GAP mSpa1 is more extensive than previously reported and spans approximately 160 amino acid residues encoded within exons 34-38 of the TSC2 gene. Single strand conformation polymorphism analysis of these exons in 173 unrelated patients with tuberous sclerosis and direct sequencing of variant conformers together with study of additional family members enabled characterisation of disease associated mutations in 14 cases. Missense mutations, which occurred in exons 36, 37 and 38 were identified in eight cases, four of whom shared the same recurrent change P1675L. Each of the five different missense mutations identified was shown to occur de novo in at least one sporadic case of tuberous sclerosis. The high proportion of missense mutations detected in the region of the TSC2 gene encoding the GAP-related domain supports its key role in the regulation of cellular growth.      

Relationship between serum follicle stimulating hormone in the male and standard sperm parameters, and the results of intracytoplasmic sperm injection

Serum follicle stimulating hormone (FSH) is routinely measured when evaluating the infertile male for intracytoplasmic sperm injection (ICSI). However, among the sperm parameters, only its relationship with sperm concentration is well documented. Few investigations concern the relationship between FSH and sperm motility and morphology, and the results of ICSI. A retrospective study of 316 couples who underwent ICSI was carried out to determine the relationships between serum FSH concentrations in the male and (i) standard sperm parameters_(concentration, motility and morphology) and (ii) fertilization, cleavage, pregnancy and implantation rates after ICSI. There was an inverse correlation with sperm concentration and total motility but no relationship was found with progressive motility and sperm morphology. Neither was any relationship found between serum FSH and fertilization, cleavage, pregnancy and implantation rates, and the results of ICSI. These findings suggest the need to review the routine measurement of serum FSH in the infertile male when ICSI is the planned treatment procedure.      

Immune reconstitution inflammatory syndrome in association with HIV/AIDS and tuberculosis: Views over hidden possibilities

Background  

CD4+ T lymphocyte (CD4) cell count testing is the standard method for determining eligibility for antiretroviral therapy (ART), but is not widely available in sub-Saharan Africa. Total lymphocyte counts (TLCs) have not proven sufficiently accurate in identifying subjects with low CD4 counts. We developed clinical algorithms using TLCs, hemoglobin (Hb), and body mass index (BMI) to identify patients who require ART.