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.     

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.      

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.      

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.     

Expression of the 5-HT1B receptor by subtypes of rat trigeminal ganglion cells

The type of trigeminal ganglion cells that express 5-HT1B receptors has not been well characterized, despite the fact that these receptors are important targets for anti-migraine drugs. We have therefore used combined in situ hybridization and immunofluorescence to examine the expression of 5-HT1B receptor messenger RNA in identified subpopulations of rat trigeminal ganglion cells. 5-HT1B-expressing cells accounted for 15% of all trigeminal ganglion cells, were medium sized, and showed immunoreactivity for either 200,000 mol. wt neurofilament, calcitonin gene-related peptide, or nerve growth factor receptor (trkA). In contrast few 5-HT1B cells showed immunoreactivity for substance P or binding of the lectin Griffonia simplicifolia IB4. Our results are consistent with 5-HT1B receptors acting to control the release of calcitonin gene-related peptide from trigeminal neurons with finely myelinated axons. 5-HT1B receptor agonists may reduce neurogenic vasodilation by activating such receptors. However many nociceptive trigeminal neurons, including the substance P and IB4-binding populations, do not express the 5-HT1B receptor.     

Effect of hyperthermia and anoxia on glucocorticoid and mineralocorticoid receptor expression in neonatal rat hippocampus

Brief periods of neonatal asphyxia are frequently observed. Within the CNS, the hippocampus is known to be particularly vulnerable to the damaging effects of hypoxia/ischaemia. The hippocampus contains the highest concentration of both mineralocorticoid (MR) and glucocorticoid (GR) receptors and the balance between MR/GR activation influences cell birth and death. MR occupation appears to promote prosurvival actions, while GR overactivation favours neurodegeneration. It has been widely recognized that core body temperature is a critical determinant of the severity of hypoxic–ischemic brain injury; indeed, hyperthermia exacerbates the degree of damage. Therefore, the aim of the present investigation was to study the effect of elevated body temperature in newborn rats under control conditions or during neonatal exposure to a critical anoxia, on changes of MR and GR mRNA expression in the rat hippocampus. 2-day-old rats were exposed to anoxia in 100% nitrogen atmosphere. Rectal temperature was kept at 33 °C (typical for the rat neonates), or elevated to a level typical for febrile (39 °C) adults. Control rats were exposed to atmospheric air under the respective thermal conditions. The changes in MR and GR mRNA expression in hippocampus were examined 24 h after exposure. Our data show that hyperthermia with or without added anoxia, causes induction of MR mRNA expression in neonatal rat hippocampus without any effect on GR mRNA expression. We suggest this elevation of MR plays an important role in modulating the survival of neurons in the injured hippocampus.     

Body mass index, migraine, migraine frequency and migraine features in women

We evaluated the association of body mass index (BMI) with migraine and migraine specifics in a cross-sectional study of 63 467 women aged ≥ 45 years, of whom 12 613 (19.9%) reported any history of migraine and 9195 had active migraine. Compared with women without migraine and a BMI < 23 kg/m², women with a BMI ≥ 35 kg/m² had adjusted odds ratios (ORs) (95% confidence intervals) of 1.03 (0.95, 1.12) for any history of migraine. Findings were similar for active migraineurs. Women with a BMI of ≥ 35 kg/m² had increased risk for low and high migraine frequency, with the highest estimate for women who reported daily migraine. Compared with women with the lowest associated risk (migraine frequency < 6 times/year; BMI between 27.0 and 29.9 kg/m²), women with a BMI ≥ 35 kg/m² had an OR of daily migraine of 3.11 (1.12, 8.67). Among the women with active migraine, a BMI ≥ 35 kg/m² was associated with increased risk of phonophobia and photophobia and decreased risk of a unilateral pain characteristic and migraine aura. Our data confirm previous findings that the association between BMI with migraine is limited to migraine frequency and specific migraine features.     

Construction of modern Australian first trimester ultrasound dating and growth charts

Accurate pregnancy dating is vital to obstetric management. However, first trimester fetal charts commonly used in Australia rely on data reported more than three decades ago. This study reports first trimester dating and growth charts for crown‐rump length between 5 and 14 weeks of gestation and biparietal diameter between 9 and 14 weeks of gestation on an Australia population using modern real‐time ultrasound equipment. All consenting eligible women attending a large Sydney clinic for first trimester ultrasound between March 2005 and December 2006 were recruited. Measurements were carried out to Australasian Society for Ultrasound in Medicine standard protocols. Statistical analyses were undertaken using polynomial regression models and thorough diagnostic checks made. Overall 396 eligible women consented to the study, with 268 between 9 and 14 weeks of gestation. The average participant age was 34 years (range 22–45 years), 371 and all yielded valid biometry measurements. Equations, means and 90% reference intervals for crown‐rump length measurements and biparietal diameter measurements were derived using polynomial regression models. Thorough residual and diagnostic checks were made. Once validated by others, we believe they will warrant consideration for use by Australasian Society for Ultrasound in Medicine.