Electrocardiographic and other cardiac anomalies in beta-glucuronidase-null mice corrected by nonablative neonatal marrow transplantation.

Cardiovascular manifestations of lysosomal storage disease (LSD) are a significant health problem for affected patients. Infantile-onset cardiac disease, because of its rapid progression, is usually treated symptomatically. Therapy in older patients includes valve replacement and bone marrow (BM) transplantation, both of which are life threatening in the already debilitated patients. Enzyme replacement therapy has potential benefit but has not yet been demonstrated to provide long-term relief for cardiac disease. Here, we demonstrate prevention of severe cardiac manifestations in beta-glucuronidase (GUSB) null mice BM-transplanted i.v. as neonates without myeloablative pretreatment. The mice, a model of mucopolysaccharidosis type VII (MPSVII, Sly syndrome), develop progressive LSD unless provided with GUSB early in life. The BM recipients retained GUSB+ donor cells in the peripheral blood and heart until necropsy at > or = 11 months of age. The enzyme beta-hexosamindase increased in tissues of GUSB null MPSVII mice was reduced significantly (P = 0.001) in treated MPSVII hearts. Electrocardiography demonstrated normalization of heart rate, PR, PQ, and QRS intervals in BM recipients. Storage was markedly reduced in the stroma of heart valves, adventitial cells of the aortic root, perivascular and interstitial cells of the myocardium, and interstitial cells of the conduction tissue. Heart/body weight ratio normalized. The aortic root was still grossly distended, and the conductive myocytes retained storage, suggesting neither plays a major role in ECG normalization. We conclude that transplantation of MPSVII neonates without toxic intervention can prevent many of the cardiovascular manifestations of LSD.

Hyperkalaemic paralysis--a bizarre presentation of renal failure.

Paralysis due to hyperkalaemia is rare and the diagnosis may be overlooked in the first instance. However it is rapidly reversible and so long as electro-cardiography and serum potassium measurement are urgently done in all patients presenting with paralysis, it will not be missed. A case of hyperkalaemic paralysis is described and a review of the emergency management discussed.

Extent and kinetics of genetic change in the omp1 gene of Chlamydia trachomatis in two villages with endemic trachoma.

Variants of Chlamydia trachomatis in two Gambian villages with hyperendemic trachoma were analyzed by omp1-based polymerase chain reaction and sequencing from conjunctival swabs. Samples collected over a 22-month period included a complete cross-sectional study of each village. Overall, 4 genovar A and 4 B variants were characterized by point mutations in the omp1 gene, resulting in changes in the inferred amino acid sequence. Two genovar A and 2 B variants accounted for 87% of the total ocular chlamydial infection in both villages. Although some flux in the prevalence of individual variants was observed overtime, their overall distribution remained remarkably stable. There was no evidence of major antigenic shift arising from recombination events at the omp1 locus as described for genital tract infection. These results indicate that omp1 variation in these two trachoma-hyperendemic communities is limited and unlikely to hamper development of trachoma vaccines based on the major outer membrane protein.

Polymerase chain reaction for the detection of ocular chlamydial infection in trachoma-endemic communities.

Polymerase chain reaction (PCR) with primers derived from the sequence of the cryptic chlamydial plasmid was evaluated for the detection of ocular chlamydial infection in trachoma-endemic populations and was used to explore further the relationship between ocular chlamydial infection and clinical signs of trachoma. It was more sensitive than other laboratory techniques, especially for mild cases of trachoma, in detecting infection in 144 (72%) of 200 who fulfilled the World Health Organization case definition. Of 1132 subjects who did not fulfill these criteria, 85 (7.5%) were PCR-positive, but about one-third of these 85 subjects had minor signs of trachoma. Clinically negative subjects who were PCR-positive were more likely than PCR-negative subjects to have acquired signs of disease at 1 and 6 months of follow-up. Clinical signs were twice as likely to have resolved after 1 month in PCR-negative subjects with disease than in those who were PCR-positive.