Muscle connective tissue content of endurance-trained and inactive individuals.

Although it is known that exercise exerts a positive regulatory effect on collagen synthesis, the effects of endurance training on muscle endomysial connective tissue in man are not so well documented. To investigate this, a single muscle biopsy was collected from two groups of volunteers - endurance-trained sports participants and age-matched healthy untrained individuals. Endomysial staining intensity of types I, III and IV collagen was quantified by immunohistochemical staining and image analysis methods. Gelatinase activity in the endomysium was also quantified histochemically. Mean cycling VO2peak values of 53+/-6 (SD) and 32+/-8 mL/kg/min (P<0.01) were recorded for the trained and untrained groups, respectively. The staining intensity of types I, III and IV collagen and gelatinase activity in the trained group were not significantly different from the untrained group. However, when the data for all 11 volunteers were pooled, significant negative correlations were found for type III collagen staining intensity and capillary/fiber ratio; and for the relationship between type IV collagen staining intensity and VO2peak. These results suggest a negative association between aerobic capacity and the intensity of staining for types III and IV collagen in muscle endomysium.

Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.

Central core disease (CCD) is a congenital myopathy due to dominant mutations in the skeletal muscle ryanodine receptor gene (RYR1). The authors report three patients from two consanguineous families with symptoms of a congenital myopathy, cores on muscle biopsy, and confirmed linkage to the RYR1 locus. Molecular genetic studies in one family identified a V4849I homozygous missense mutation in the RYR1 gene. This report suggests a congenital myopathy associated with recessive RYR1 mutations.

Variable presentation of primary hyperoxaluria type 1 in 2 patients homozygous for a novel combined deletion and insertion mutation in exon 8 of the AGXT gene.

Two unrelated patients of Pakistani origin presented with primary hyperoxaluria type 1 (PH1) at 4 months and 3 years of age, respectively. While the younger patient failed to thrive and suffered from early renal failure, the older one showed a relatively benign history with urolithiasis as the main feature of the disease. In both patients the diagnosis was confirmed by assessment of alanine:glyoxylate aminotransferase catalytic and immunoreactivity in liver biopsy specimens. The underlying genetic defect was found to be a combined deletion and insertion in exon 8 which alters the reading frame of the protein. The nucleotide change introduces a Stu1 restriction site which facilitated typing of additional family members. Both patients and a further affected brother were homozygous for this mutation, while their parents were heterozygous for it. This mutation is the first deletion/insertion identified in PH1. Although rare in our PH1 patient cohort (2.5% of alleles), the finding of 2 homozygous apparently unrelated individuals of the same ethnic origin suggests that it may prove worthwhile to screen other Asian patients for this mutation. These PH1 cases present further evidence that factors other than genotype contribute significantly to the clinical presentation and severity of PH1.

Nasopharyngeal carcinoma in children.

The results of treatment are reviewed in 18 cases of childhood nasopharyngeal carcinoma. Since 1976 adjuvant chemotherapy with cyclophosphamide, methotrexate, and adriamycin has been used in Manchester and Leeds. The outcome is compared in 9 patients treated with radiotherapy alone and 9 patients treated later with both radiotherapy and adjuvant chemotherapy. Relapse-free survival rates were 0% for those treated with radiotherapy alone and 78% at 13-80 months after diagnosis for those treated with both radiotherapy and chemotherapy. It is concluded that adjuvant chemotherapy improves relapse-free survival in childhood nasopharyngeal carcinoma.