Progressive ataxia due to a missense mutation in a calcium-channel gene

We describe a family with severe progressive cerebellar ataxia involving the trunk, the extremities, and speech. The proband, who has prominent atrophy of the cerebellum, shown by magnetic resonance imaging, was confined to a wheelchair at the age of 44 years. Two sons have episodes of vertigo and ataxia that are not responsive to acetazolamide. Quantitative eye-movement testing showed a consistent pattern of abnormalities localizing to the cerebellum. Genotyping suggested linkage to chromosome 19p, and SSCP showed an aberrant migrating fragment in exon 6 of the calcium-channel gene CACNA1A, which cosegregated with the disease. Sequencing of exon 6 identified a G-->A transposition in one allele, at nucleotide 1152, resulting in a predicted glycine-to-arginine substitution at codon 293. The CAG-repeat expansion associated with spinocerebellar ataxia 6 was not present in any family members. This family is unique in having a non-CAG-repeat mutation that leads to severe progressive ataxia. Since a great deal is known about the function of calcium channels, we speculate on how this missense mutation leads to the combination of clinical symptoms and signs.     

Prevalence of high-risk sex among HIV-positive gay and bisexual men: a longitudinal analysis

INTRODUCTION: This longitudinal study examined the prevalence and demographic correlates of unprotected insertive and receptive anal intercourse among HIV-positive gay and bisexual men who were aware of their serostatus. METHODS: Participants (n = 395), sampled randomly at two HIV outpatient clinics in Los Angeles, completed two waves of self-administered questionnaires (separated by approximately 7-9 months) that measured sexual behaviors in the previous 60 days. RESULTS: The cross-sectional prevalence of unprotected insertive anal intercourse was 11.2% at time 1 and 7.1% at time 2. Longitudinal analysis indicated that nearly 15% of the participants had engaged in that high-risk behavior either at time 1 or time 2 and approximately 4% had engaged in the behavior at each time period. Similar rates of unprotected receptive anal intercourse were observed. These high-risk activities were more prevalent with seropositive and unknown serostatus partners than with seronegative partners. The rate of anal intercourse risk behaviors was higher among asymptomatic men and among those who were exclusively gay. CONCLUSION: The findings demonstrate considerable differences in the prevalence of stable and occasional high-risk sexual behaviors among HIV-positive gay and bisexual men. Simple cross-sectional analyses cannot capture the stability or variation in behavior across time and, thus, may generate misleading conclusions about disease transmission, especially if the partner's HIV serostatus is not considered in the analysis. The findings indicate a need for focused safer-sex interventions for seropositive men. The HIV outpatient clinic is an ideal setting for such interventions.     

Aortic and lower-extremity arterial disease: evaluation with MR angiography versus conventional angiography

BACKGROUND: Few data are available regarding the impact of improved depression treatment on daily functioning and disability. METHODS: In two studies of more intensive depression treatment in primary care, patients initiating antidepressant treatment were randomly assigned to either usual care or to a collaborative management programme including patient education, on-site mental health treatment, adjustment of antidepressant medication, behavioural activation and monitoring of medication adherence. Assessments at baseline as well as 4 and 7 months included several measures of impairment, daily functioning and disability: self-rated overall health, number of bodily pains, number of somatization symptoms, changes in work due to health, reduction in leisure activities due to health, number of disability days and number of restricted activity days. RESULTS: Average data from the 4- and 7-month assessments in both studies, intervention patients reported fewer somatic symptoms (OR 0.68, 95% CI 0.46, 0.99) and more favourable overall health (OR 0.50, 95% CI 0.28, 0.91). While intervention patients fared better on other measures of functional impairment and disability, none of these differences reached statistical significance. CONCLUSIONS: More effective acute-phase depression treatment reduced somatic distress and improved self-rated overall health. The absence of a significant intervention effect on other disability measures may reflect the brief treatment and follow-up period and the influence of other individual and environmental factors on disability.