Autosomal recessive idiopathic torsion dystonia in a kindred of mixed ancestry

A family with idiopathic torsion dystonia (dystonia musculorum deformans) was seen in a peripheral clinic in the Richtersveld in the north-western Cape. This rare inherited form of neurological disease has maximal prevalence in individuals of Ashkenazi Jewish ancestry, and there is controversy regarding the exact mode of inheritance. The kindred documented in this study was of mixed ancestry (Cape Coloured), and autosomal recessive inheritance was suggested by the finding of affected male and female siblings born to normal parents in an isolated inbred community.     

Social class, marital status, and cancer of the uterine cervix in England and Wales, 1950-1983.

STUDY OBJECTIVE--The aim was to investigate whether trends in mortality from cancer of the cervix uteri by age, marital status, and social class are compatible with current beliefs about the epidemiology of the disease. DESIGN--Data on mortality from cancer of the cervix for single and married women by age and social class were obtained from the Registrar General's Decennial Supplements on occupational mortality for the years 1950-53, 1959-63, 1970-72, and 1979, 1980, 1982, and 1983. Age standardised mortality rates were calculated directly by social class and marital status. SETTING--The data relate to all cases of carcinoma of the cervix reported in England and Wales in the years studied. MAIN RESULTS--There was a marked convergence of mortality between single and married women over the period within every social class grouping examined. The social class differential, however, remained essentially unchanged for both single and married women considered separately. CONCLUSIONS--Trends in mortality by marital status appear to reflect accurately the changes in the pattern of marriage and sexual behaviour that have taken place in the post-war period, whereas the patterns of other risk and protective factors such as screening explain these trends less well. In contrast, it seems likely that factors other than patterns of sexual behaviour and screening operate to maintain the social class differential in England and Wales.     

New therapies for systemic lupus erythematosus

In the past 40 years, prognosis for patients with systemic lupus erythematosus (SLE) has improved, with 10-year survival now approximately 90%. This is due probably to a combination of earlier disease diagnosis and diagnosis of milder disease, due in part to availability of multiple serological tests for SLE, use of steroids and other immunosuppressive agents, and availability of renal dialysis and transplantation. Despite this, however, the potential for significant morbidity and mortality remains in the group of patients with partially responsive or treatment resistant disease. More recently, advancements in the understanding of molecular mechanisms involved in the pathogenesis of SLE have translated to the development of novel therapies, offering possible alternatives to this patient cohort. Discussion of these pharmacological options and ongoing research forms the basis of this review.     

New therapies for rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease, which continues to cause significant morbidity in affected persons. In the past few years, a number of new exciting therapeutic options have become available. These reflect the application of knowledge obtained from advancements in understanding of disease pathogenesis and underlying molecular mechanisms. A number of these therapies are outlined in the following review, including the various biological modifiers, in particular, anti-tumour necrosis factor-alpha agents and interleukin-1 (IL-1) receptor antagonists, which have been developed in recognition of the role of pro-inflammatory cytokines in RA. Also notable, is the current interest centring on the development and trials with B cell depletion therapies, specifically rituximab, in patients with RA. This demonstrates acknowledgment for a more significant role for B cells in the aetiology of RA, in contrast to the long held view that RA was a predominantly T cell mediated disease. To evaluate this therapeutic option for RA, salient features from recent rituximab trials have been collated. Finally, a selection of other therapeutic alternatives, including anti-IL-6 receptor monoclonal antibody and tacrolimus, and newer anti-rheumatic therapies presently in development are summarized.     

An analytical model applied to a multicenter pneumococcal enzyme-linked immunosorbent assay study

Pneumococcal conjugate vaccines will eventually be licensed after favorable results from phase III efficacy trials. After licensure of a conjugate vaccine for invasive pneumococcal disease in infants, new conjugate vaccines will likely be licensed primarily on the basis of immunogenicity data rather than clinical efficacy. Analytical methods must therefore be developed, evaluated, and validated to compare immunogenicity results accurately within and between laboratories for different vaccines. At present no analytical technique is uniformly accepted and used in vaccine evaluation studies to determine the acceptable level of agreement between a laboratory result and the assigned value for a given serum sample. This multicenter study describes the magnitude of agreement among 12 laboratories quantifying an identical series of 48 pneumococcal serum specimens from 24 individuals (quality-control sera) by a consensus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) developed for this study. After provisional or trial antibody concentrations were assigned to the quality-control serum samples for this study, four methods for comparison of a series of laboratory-determined values with the assigned concentrations were evaluated. The percent error between assigned values and laboratory-determined concentrations proved to be the most informative of the four methods. We present guidelines that a laboratory may follow to analyze a series of quality-control sera to determine if it can reproduce the assigned antibody concentrations within an acceptable level of tolerance. While this study focused on a pneumococcal IgG ELISA, the methods that we describe are easily generalizable to other immunological assays.     

Dandy-Walker malformation (variant), cystic dysplastic kidneys, and hepatic fibrosis: a distinct entity or Meckel syndrome?

Dandy-Walker malformation is an unusual finding in Meckel syndrome, which characteristically presents with encephalocele, polydactyly, and cystic renal disease. We report on a family in which three nonviable brothers had Dandy-Walker malformations (variant) with associated enlarged cystic dysplastic kidneys and hepatic fibrosis. The consistent segregation of these abnormalities in all three sibs in the absence of polydactyly and encephalocele suggested the possibility of a distinct syndrome. The clinicopathological findings of the disorder are described and discussed in the context of the phenotypic spectrum of Meckel syndrome.