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.      

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

The cost of moving with the left hand

Precise left-hand movements take longer than right-hand movements (for right-handers). To quantify how left-hand movements are affected by task difficulty and phase of movement control, we manipulated the difficulty of repetitive speeded aiming movements while participants used the left or right hand. We observed left-hand costs in both initial impulse and current control phases of movement. While left-hand cost during the initial impulse phase was small, left-hand cost during the current control phase varied from 10 to 60 ms, in direct proportion to the movement’s difficulty as quantified by Fitts’ law (0.77 < R ² < 0.99, across three experiments). In particular, in comparison with a difficult task for the right hand (Fitts’ ID_R = 6.6), the left hand’s task would have to be made easier by 0.5 bits (ID_L = 6.1) to be performed as quickly. The left-hand cost may reflect the time required for callosal transfer of information between the left and right hemispheres during the current control phase of precision left-hand movements or reflect movement control differences in the current control phase of movement that are inherent to the hemispheres. Overall, the present results support multiphase models of movement generation, in which separate specialized processes contribute to the launching and completion of precision hand movements.     

Visual acuity and retinal function in patients with Bardet-Biedl syndrome

OBJECTIVE:

Bardet-Biedl syndrome is a genetic, multisystem disorder that causes severe visual impairment. This condition is characterized by retinal dystrophy, obesity, digit anomalies, renal disease, and hypogonadism. The purpose of this study was to analyze visual acuity and full-field electroretinogram findings in patients with the Bardet-Biedl syndrome phenotype.

METHODS:

The visual acuity of a group of 23 patients (15 males) with ages ranging from 6-36 years (mean = 15.8±6.4; median = 14.7) was assessed. Retinal function was evaluated by full-field electroretinography, and dark-adapted thresholds were assessed.

RESULTS:

Visual acuity in the better-seeing eye was 20/40 or better in 5 patients (21.7%), 20/50-20/150 in 13 (56.5%) patients, 20/200-20/400 in 2 (8.7%) patients and worse than 20/400 in one (4.3%) patient. The mean acuity in the better-seeing eye was 0.7±0.6 logMAR (20/100, Snellen equivalent). Scotopic rod and maximal responses were non-detectable in 21 (91.3%) patients, and cone responses were non-detectable in 15 (65.2%) patients. Elevated dark-adapted visual thresholds were observed in all 19 patients who were able to be assessed, with 10 (52.6%) patients having thresholds greater than 30 dB.

CONCLUSIONS:

In a relatively young cohort of patients with Bardet-Biedl syndrome, only 21% had 20/40 or better vision. ERG scotopic responses were absent in the majority of cases, with cone responses being observed in less than half of cases. These findings showed the early deleterious effects in retinal function and visual acuity caused by this condition.     

Dengue virus and other arboviruses: a global view of risks

Arboviruses (arthropod-borne viruses) are an ecological group of viruses from different families (e.g. Bunyaviridae, Flaviviridae and Togaviridae) that use arthropods such as mosquitoes, flies and ticks as vectors for transmission between different hosts. The superb plasticity of these viruses allows propagation to different host systems including both invertebrates and vertebrates. More than 500 species of arbo-virus have been described and are listed in the International Catalogue of arbo-virus ( http://www.cdc.gov/nczved/divisions/dvbid/arbovirus.html ), many of which are of medical importance. Globally, arboviral infections have become increasingly common and human diseases caused by these infections have expanded their frontiers in the last few decades emerging in places with no previous history of epidemic activity or localised transmission of a specific arbovirus. One example is the recent arrival of West Nile virus (WNV) in the Western Hemisphere and its subsequent propagation in the Americas. Arboviral diseases are also re-emerging in places where the disease had previously been well-controlled or eradicated, resulting in an increasing number of cases and more severe forms of disease in endemic regions. Human infections with arboviruses are mostly asymptomatic, but symptomatic infections can range from malaise, mild febrile illness (with flu-like symptoms) to severe disease that may progress to long-term physical or cognitive impairment and/or mortality. Arboviral infections have an incubation period during which viral replication with a viremic phase takes place in the absence of symptoms. Viremic blood has the potential to transmit infection to blood recipients and therefore arboviruses can pose a threat to the safety of the blood supply. For instance, during an epidemic, asymptomatic individuals may donate blood and transmit the infection to blood component recipients. Among the arboviral infections that have been on the radar for increased activity in the last decade are: WNV, Dengue viruses (DENV) and Chikungunya virus (CHIKV). In addition, other arboviral infections such as Yellow Fever, Saint Louis encephalitis, Tick-borne encephalitis, Rift Valley fever, Japanese encephalitis, Powassan encephalitis, Murray Valley encephalitis and Zika fever have been reported as emerging or re-emerging in various areas around the globe. Alertness and surveillance are required to allow implementation of measures to mitigate risk of transmission to blood recipients including blood screening tests when available and appropriate. In addition, the evidence of increased arbovirus activity worldwide points to the critical need for the development of affordable diagnostic and screening assays with high sensitivity and specificity as well as new vaccines and therapies, since most populations at risk reside in less privileged parts of the world. The need for these tools is pressed by the imminent possibility of outbreaks in any part of the world due to the combination of expanding distribution of vectors and increased mobility of infected hosts by travel and trade.     

Risk-based fluconazole prophylaxis of <Emphasis Type="Italic">Candida</Emphasis> bloodstream infection in a medical intensive care unit

Candida bloodstream infection (CBSI) accounted for 50% of bloodstream infections in our medical intensive care unit (MICU) in 2004. Our objective was to evaluate a risk-based fluconazole prophylaxis program. CBSI incidence, patient demographics, and unit metrics were retrospectively reviewed for 2004. Starting on January 2005, patients meeting pre-specified criteria were placed on risk-based fluconazole prophylaxis and their outcomes, adverse events, and unit metrics were prospectively collected. The inclusion criteria were based on a clinical prediction rule and included an MICU stay greater than 72 h, broad-spectrum antibiotics, and central venous catheter, along with at least two of the following: mechanical ventilation for at least 48 h, any type of dialysis, parenteral nutrition, pancreatitis, systemic steroids, or other systemic immunosuppressive agents. For 2004, the unit had nine CBSI, corresponding to a rate of 3.4 CBSI/1,000 line-days. Four cases were caused by C. albicans, four by C. glabrata, and one by C. tropicalis. The mean ± standard deviation (SD) APACHE II score for these patients was 25 ± 9. In 2005, a total of 36 patients (2.6% of all unit admissions) received prophylaxis and the unit had two CBSI, corresponding to a rate of 0.79 CBSI/1,000 line-days. One patient had C. albicans and the other had C. tropicalis. The mean ± SD APACHE II score for these patients was 21 ± 8. The mean ± SD duration of fluconazole prophylaxis was 8 ± 6 days. Fluconazole was discontinued in two patients due to non-severe adverse events (acute eosinophilia, elevated transaminases). The attributable cost of CBSI in the unit in 2004 was $63,000 per episode. The total cost for the 36 courses of fluconazole was $6,000. When comparing the 2004 CBSI patients and the 2005 prophylaxis patients, we found similar acuity, demographics, and risk factors, with no differences in MICU or hospital mortality or length of stay. Risk-based fluconazole prophylaxis in an MICU with a high incidence of CBSI was safe and cost-effective when applied to a limited number of patients and produced a significant decrease in the incidence of this disease.     

二甲双胍和瑞格列奈对非肥胖的2型糖尿病患者非血糖性心血管危险标志的影响比较

在2型糖尿病患者中，反映炎症和内皮功能障碍的生物标志已经与心血管疾病和代谢调节联系起来。二甲双胍和促胰岛素分泌剂被证明有相同的抗高血糖作用。此研究比较了二甲双胍和促胰岛素分泌剂瑞格列奈在非肥胖的2型糖尿病患者的心血管疾病生物标志上的效能。     

Meningitis and midline facial deformity

A baby with unilateral cleft lip, midline cleft palate and hypertelorism developed meningitis in the first 48 h of life. Examination of the nasopharynx showed a soft tissue mass, which was confirmed as a basal encephalocele by computed tomography. There was also congenital hydrocephalus and the corpus callosum was absent. Surgical treatment included repair of the anterior basal skull defect, repair of the lip and palate, and ventriculo-peritoneal shunt. There is currently evidence of developmental delay and right-sided visual impairment due to Morning Glory syndrome. This case demonstrates that basal encephalocele should be considered in any baby with midline facial deformity who develops meningitis.