Knee extensor strength differences in obese and healthy-weight 10-to 13-year-olds

The purpose of this study was to investigate if obese children have reduced knee extensor (KE) strength and to explore the relationship between adiposity and KE strength. An observational case–control study was conducted in three Australian states, recruiting obese [N = 107 (51 female, 56 male)] and healthy-weight [N = 132 (56 female, 76 male)] 10- to 13-year-old children. Body mass index, body composition (dual energy X-ray absorptiometry), isokinetic/isometric peak KE torques (dynamometry) and physical activity (accelerometry) were assessed. Results revealed that compared with their healthy-weight peers, obese children had higher absolute KE torques (P ≤ 0.005), equivocal KE torques when allometrically normalized for fat-free mass (FFM) (P ≥ 0.448) but lower relative KE torques when allometrically normalized for body mass (P ≤ 0.008). Adjustments for maternal education, income and accelerometry had little impact on group differences, except for isometric KE torques relative to body mass which were no longer significantly lower in obese children (P ≥ 0.013, not significant after controlling for multiple comparisons). Percent body fat was inversely related to KE torques relative to body mass (r = ?0.22 to ?0.35, P ≤ 0.002), irrespective of maternal education, income or accelerometry. In conclusion, while obese children have higher absolute KE strength and FFM, they have less functional KE strength (relative to mass) available for weight-bearing activities than healthy-weight children. The finding that FFM-normalized KE torques did not differ suggests that the intrinsic contractile properties of the KE muscles are unaffected by obesity. Future research is needed to see if deficits in KE strength relative to mass translate into functional limitations in weight-bearing activities.     

Moderation of hemophilia A phenotype by the factor V R506Q mutation

Although many examples of unrelated hemophilia A patients carrying identical point mutations in the factor VIII (FVIII) gene have been reported, the clinical phenotype is not always the same among patients sharing the same molecular defect. Possible explanations for this discrepancy include undetected additional mutations in the FVIII gene or coinheritance of mutations at other genetic loci that modulate FVIII function. We report molecular genetic analysis of potential modifying genes in two sets of unrelated patients carrying common FVIII missense mutations but exhibiting different levels of clinical severity. Both mutations (FVIII R1689C and R2209Q) are associated with severe hemophilia A in some patients and mild/moderate disease in others. The common von Willebrand disease type 2N mutation (R91Q) was excluded as a modifying factor in these groups of patients. However, analysis of the recently described factor V (FV) R506Q mutation (leading to activated protein C resistance) identified a correlation of inheritance of this defect with reduced hemophilia A severity. Two moderately affected hemophilia A patients, each with either of two FVIII gene mutations, were heterozygous for FV R506Q, whereas two severely affected patients and two moderately affected patients were homozygous normal at the FV locus. Our results suggest that coinheritance of the FV R506Q mutation may be an important determinant of clinical phenotype in hemophilia A and that modification of the protein C pathway may offer a new strategy for the treatment of FVIII deficiency.     

Comprehensive evaluation of two HLA‐B17 monoclonal antibodies for flow cytometry‐based HLA‐B57/B58 screening prior to abacavir prescription

Hypersensitivity reactions to the drug abacavir, used to treat HIV/AIDS patients, is associated with possession of HLA‐B*57:01. We have carefully assessed two commercially available HLA‐B57/B58 murine monoclonal antibodies [0196HA and BIH0243 (One Lambda Inc.)] in a simple flow cytometry‐based assay. The evaluation involved tests on 228 reference and random samples covering 91% of all WHO recognized HLA‐A, B and C specificities. These involved donors with six different HLA‐B*57 alleles and included 19 examples of B*57:01. Both antibodies unambiguously detected B57, but there were small difference in their reactivity against B57‐positive non‐B*57:01 samples. Importantly, there was no reactivity against B57/B58‐negative samples. The possible amino acid motifs involved in the reactivity of these antibodies with B57/B58 were delineated. Thus, HLA‐B57/B58, normally present in <10% of patients, can be easily recognized using these two antibodies and further tested by a DNA‐based typing method to identify B*57:01.     

Sudden cardiac death and tuberculosis – How much do we know?

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major killer in the world and pulmonary infections are well characterised. It is not widely known that TB myocarditis leads to sudden cardiac deaths (SCD), especially in young people. Unlike other causes of SCD, risk factors such as family history are absent and patients are asymptomatic. This makes risk stratification and interventions with implantable cardiac defibrillators extremely difficult. Only a few cases of TB myocarditis SCD have been reported since 1977 and all of which were diagnosed at autopsy. The majority of reports showed extensive TB infiltration of the myocardium with no systemic symptoms. Concurrent miliary or systemic TB was postulated to be the source of TB myocarditis. The mechanism of death has been hypothesized to be ventricular tachyarrhythmia. Pulmonary TB has also been reported to cause sudden death. However, ventricular arrhythmias have not been recorded, suggesting a different mechanism to TB myocarditis SCD, which centres upon cardiopulmonary collapse leading to bradycardia. Although anti-tuberculous chemotherapy is efficacious in the treatment of TB myocarditis, there is no evidence to suggest that it is effective in the prevention of SCD. It remains to be seen whether better global control of TB disease burden will result in reductions in SCD. Furthermore, no experimental data exist on the link between TB myocarditis SCD and arrhythmias. We propose a unifying diagnostic system for TB myocarditis based on the current data and molecular techniques. This is likely to require updates as more evidence becomes available.