Late onset in dysferlinopathy widens the clinical spectrum.

LGMD2B, Miyoshi Myopathy and Distal Anterior Compartment Myopathy are caused by mutations in the dysferlin gene (DYSF) leading to progressive muscular weakness and wasting with onset usually within the second or third decade of life. We here present a patient with disease onset at 73 years. The presenting symptom was exercise-induced stiffness of the trunk and proximal leg muscles without major progression over a period of 12 years. Gastrocnemius muscle biopsy revealed dystrophic morphology and biochemical depletion of dysferlin, while sequence analysis revealed compound heterozygous splicing mutations of the dysferlin gene. This case represents the eldest age of onset of dysferlinopathy reported so far and widens the clinical spectrum of this disease.

Enzyme replacement therapy in classical infantile pompe disease: results of a ten-month follow-up study.

Infantile Pompe disease (IPD) is a fatal, autosomal recessive muscle-wasting disorder. Due to a deficiency of the lysosomal enzyme acid alpha-glucosidase patients develop a generalized myopathy, diaphragmatic weakness, and cardiomyopathy leading to death usually within the first year of life. So far there is no therapy available. We report on the safety and efficacy of transgenically derived recombinant human precursor acid alpha-glucosidase (rhGAA) in a 10-month follow-up study in two children with IPD who previously completed a 48-week course of enzyme replacement therapy (ERT) with the same medication at the same dose in a phase II clinical trial. Under this therapy cardiac status and muscle strength had improved, leading to survival beyond the age of one year. These results, together with data from two other phase II clinical trials encouraged further evaluation of the long-term safety and efficacy of enzyme replacement therapy in patients with infantile-onset Pompe disease. During the 10-month follow-up period, ERT was well-tolerated and neither patient experienced a single infusion-associated reaction. The initial improvements in cardiac size and function, as measured by left ventricular mass index and the fractional shortening, were maintained in both patients, and a continued improvement of motor function, as measured by the Alberta infant motor scale, was observed.

Safety and efficacy of recombinant acid alpha-glucosidase (rhGAA) in patients with classical infantile Pompe disease: results of a phase II clinical trial.

Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. Due to virtual absence of acid alpha-glucosidase, patients with classical infantile Pompe disease develop progressive cardiomyopathy, skeletal muscle weakness and respiratory insufficiency leading to death in early infancy. We report on the results of a phase II clinical trial including two patients with classical infantile Pompe disease receiving enzyme replacement therapy over a period of 48 weeks by weekly infusions. Recombinant acid alpha-glucosidase was derived from the milk of transgenic rabbits. Safety was evaluated by recording adverse events while clinical efficacy was evaluated by ventilator-free survival, left ventricular mass index, motor development as well as histologic and biochemical analysis of muscle biopsies. This therapy was in general well-tolerated. There was an overall improvement in left ventricular mass, cardiac function, skeletal muscle function and histological appearance of skeletal muscle.

Microlissencephaly in microcephalic osteodysplastic primordial dwarfism: a case report and review of the literature.

Microcephalic osteodysplastic primordial dwarfism (MOPD) is defined as a syndrome presenting with intrauterine and postnatal growth retardation, typical facial appearance, skeletal dysplasia and brain abnormalities. Autosomal-recessive inheritance is suspected. Sharing clinical manifestations, the former type III has been accepted to be the same entity as type I. We present the case of a male infant with MOPD I and micrencephaly with simplified gyral pattern to a degree defining it as microlissencephaly (MLIS). The brain abnormalities in MOPD I have not yet been classified. Reviewing the literature, we conclude that microlissencephaly appears to be the distinct developmental brain abnormality in MOPD I. Conversely, osteodysplastic changes have to be taken into consideration in the differential diagnosis of microlissencephaly. In addition, our patient suffered from acute lymphatic leukaemia which has not previously been described in association with MOPD I.

Quadruplication of the ureter in combination with a large ureteral cyst.

A newborn female was found to have a quadruplication of the ureter: four proximal, slim ureters opened into a large ureteral cyst and a distal monoureter opened into the bladder. Only five cases of ureteral quadruplication have been reported in the literature, one of which presented with identical pathology. These two cases may have been caused by similar, unidentified abnormal embryonic development.

[Antibiotic treatment of travellers' diarrhea]. / Antibiotikabehandling af rejsediaré.

UNLABELLED: This review should be cited as: De Bruyn G, Hahn S, Borwick A. Antibiotic treatment for travellers' diarrhoea (Cochrane Review). In: The Cochrane Library, Issue 1, 2001. Oxford: Update Software. A substantive amendment to this systematic review was last made on 21 May 2000. Cochrane reviews are regularly checked and updated if necessary. BACKGROUND: Traveller's diarrhoea is a syndrome frequently encountered in persons crossing an international boundary. Diarrhoea can lead to significant discomfort and interference with travel plans. Bacterial pathogens are a frequent course of this syndrome. Several antibiotics have been tested for efficacy in reducing the duration and severity of the illness. OBJECTIVES: The aims of the review were to access the effects of antibiotics on traveller's diarrhoea in relation to the duration of illness, severity of illness, and adverse effects of medications. SEARCH STRATEGY: The Cochrane Collaboration Trials Register, MEDLINE, and EMBASE were searched. Additional trials were identified by hand searching. Content experts were contacted. SELECTION CRITERIA: All trials in any language in which travellers older than five years were randomly allocated to treatment for acute non-bloody diarrhoea with antibiotics and where the causative organism is not known at allocation. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and extracted data. MAIN RESULTS: Twenty published studies met inclusion and quality criteria for inclusion. Twelve studies were placebo-controlled. A meta-analysis for the primary outcome was not feasible. All of the ten trials reported a significant reduction in duration of diarrhoea in participants treated with antibiotics compared with placebo. Data from two trials demonstrated a small reduction for antibiotic treated patients in the number of unformed stools passed per each 24 hour period from randomisation up to 72 hours. Data from six trials demonstrated a greater number of participants being cured of diarrhoea by 72 hours (odds ratio [OR] 5.9, 95% confidence interval [CI] 4.06 to 8.57). Data regarding side effects were available from five trials. There was wide variation in the prevalence of side effects reported in different trials. Persons taking antibiotics experienced more side effects than those taking placebo (OR 2.37, 95% CI 1.5 to 3.75). REVIEWERS' CONCLUSION: Antibiotic treatment is associated with shorter duration of diarrhoea but higher incidence of side effects. Trials generally do not report duration of post-treatment diarrhoea using time-to-event analyses, and should do.