Analgesic nephropathy in Hungary: the HANS study.

BACKGROUND: The diagnosis of analgesic nephropathy has improved significantly with modern imaging techniques. We reviewed a large portion of the Hungarian dialysis population to obtain additional insight into the problem. METHODS: Twenty-two participating dialysis units enrolled 1400 patients on renal replacement therapy between 1 January 1995 and 1 January 1998. Patients with no known aetiology (n = 284) were interviewed and studied with renal imaging. We assessed the presence of decreased renal mass combined with either bumpy contours, papillary calcification, or both. The subjects studied were interrogated extensively. RESULTS: Our survey suggested analgesic nephropathy in 47 of 1400 patients (3.3%), 3-fold higher than the EDTA database estimate for Hungary. The analgesics most commonly abused were phenacetin-containing mixtures. The driving symptoms were mainly headache and joint pain. Cardiovascular complications were more common than in the rest of the dialysis population, independent of smoking and lipid values (P<0.01). CONCLUSIONS: Phenacetin should be banned. Our study results support the need for longitudinal cohort and case-control studies in Hungary.     

Pentoxifylline treatment of mice with chronic pulmonary tuberculosis accelerates the development of destructive pathology

It is well established in animal models that production of the cytokine tumour necrosis factor-alpha (TNF-alpha) is essential to the proper expression of acquired specific resistance following infection with Mycobacterium tuberculosis. This gives rise to an apparent state of chronic disease which over the next 100-200 days is characterized by slowly worsening pathological changes in the lung. To determine whether continued TNF-alpha production was harmful during this phase mice were treated with a TNF-alpha inhibitor, pentoxifylline. It was observed that although this therapy did not alter the numbers of bacteria recovered from the lungs of the infected mice, tissue damage within the lung was accelerated. These data thus demonstrate that production of TNF-alpha, already known to be important during the early expression of resistance to tuberculosis, remains important and beneficial during the chronic stage of the disease.     

Role of Clostridium perfringens phospholipase C in the pathogenesis of gas gangrene.

Gas gangrene is an acute and devastating infection most frequently caused by Clostridium perfringens and characterized by severe myonecrosis, intravascular leukocyte accumulation, and significant thrombosis. Several lines of evidence indicate that C. perfringens phospholipase C (Cp-PLC), also called alpha-toxin, is the major virulence factor in this disease. This toxin is a Zn²⁺ metalloenzyme with lecithinase and sphingomyelinase activities. Its three dimensional structure shows two domains, an N-terminal domain which contains the active site, and a C-terminal domain required for the Ca²⁺dependent interaction with membranes. Cp-PLC displays several biological activities: it increases capillary permeability, induces platelet aggregation, hemolysis, myonecrosis, decreases cardiac contractility, and is lethal. Experiments with genetically engineered Cp-PLC variants have revealed that the sphingomyelinase activity and the C-terminal domain are required for toxicity. The myotoxicity of Cp-PLC is largely dependent on its membrane damaging effect. In addition, it has been suggested that the alterations in the blood flow induced by this toxin also contribute to muscle damage. In gas gangrene, Cp-PLC dysregulates transduction pathways in endothelial cells, platelets and neutrophils leading to the uncontrolled production of several intercellular mediators and adhesion molecules. Thus, Cp-PLC alters the traffic of neutrophils to the infected tissue and promotes thrombotic events, enhancing the conditions for anaerobic growth.     

Standardized Ultrasound Measurement of Subcutaneous Fat Patterning: High Reliability and Accuracy in Groups Ranging from Lean to Obese

A recently standardized ultrasound technique for measuring subcutaneous adipose tissue (SAT) was applied to normal-weight, overweight and obese persons. Eight measurement sites were used: upper abdomen, lower abdomen, erector spinae, distal triceps, brachioradialis, lateral thigh, front thigh and medial calf. Fat compression was avoided. Fat patterning in 38 participants (body mass index: 18.6–40.3 kgm^?2; SAT thickness sums from eight sites: 12–245 mm) was evaluated using a software specifically designed for semi-automatic multiple thickness measurements in SAT (sound speed: 1450 m/s) that also quantifies embedded fibrous structures. With respect to ultrasound intra-observer results, the correlation coefficient ρ = 0.999 (p < 0.01), standard error of the estimate = 1.1 mm and 95% of measurements were within ±2.2 mm. For the normal-weight subgroup, the median measurement deviation was 0.43 mm (1.1% of mean thickness), and for the obese/overweight subgroup it was 0.89 mm (0.5%). The eight sites used here are suggested to represent inter-individual differences in SAT patterning. High measurement accuracy and reliability can be obtained in all groups, from lean to overweight and obese, provided that measurers are trained appropriately.     

Short-term effectiveness of a community-implemented falls prevention referral service

Purpose: To evaluate the effectiveness of the 16-week evidence-based Steady Steps exercise referral scheme at improving physical function, balance confidence, and quality of life (QoL) of community-dwelling older adults at risk of falling.

Method: A non-experimental, practice-based study involving a retrospective analysis of participant outcomes. Pre–post comparisons of three performance-based measures of gait and balance and of person-reported outcomes for balance confidence and QoL were performed. Effectiveness was evaluated in terms of statistically significant changes and relative to published fall-risk thresholds and minimal detectable changes (MDCs) or minimum clinically important differences.

Results: One hundred and thirty-six participants completed the program over 19?months. Statistically significant differences were observed for all outcomes (p?40% reported clinically important improvements in QoL.

Conclusions: While the non-experimental design precludes conclusive evidence of causation, the highly significant and clinically meaningful improvements observed in individuals who completed the evidence-based Steady Steps program support its translation of evidence into effective practice. Continued implementation and evaluation of such practices and their longer-term effects are warranted.

• Implications for Rehabilitation

• Falls in older adults represent an escalating public health problem, and rehabilitation professionals are charged with developing and/or identifying feasible and effective evidence-based programs that target and reduce falls risk in this population.

• Our findings support Steady Steps as an effective third-sector referral rehabilitation service that successfully translates research evidence-based exercise interventions into effective practice, positively impacting physical function, balance confidence and quality of life (QoL) in community-dwelling older adults.

• Our study provides practice-based evidence of the effectiveness of exercise interventions that are progressively challenging, deliver a high dose of moderate to high intensity and target the main falls risk factors of muscle weakness and gait and balance impairment.

• In spite of their limitations, non-experimental, practice-based approaches provide rehabilitation professionals with feasible opportunities for evaluating existing services, such as Steady Steps, and contributing to the overall evidence-base for falls prevention and management.