Prognosis in patients with Duchenne muscular dystrophy (DMD) is guarded and most deaths are due to cardiac or respiratory causes. It is unclear if some DMD gene mutations might be predictive of either mild or severe cardiac dysfunction. We studied 75 patients with DMD followed at our institution. Cardiac function, as assessed by yearly echocardiography, showed marked variability in left ventricular (LV) function. Some patients in their 3rd decade had no or minimal dysfunction whereas others in their 2nd decade had very severe dysfunction. Therefore, 4 Severity Groups were defined ranging from no/mild LV dysfunction to severe LV dysfunction using patient age at first abnormal echocardiogram and degree of LV dysfunction. Genetic data were collected for all patients. The majority of patients had mutations between exon 1 – 20 and exon 41 – 55. The distribution of the 4 Severity Groups of LV dysfunction did not significantly differ among these two mutation groups. An analysis based on the number of exons involved (< 5 exons versus ≥ 5 exons) also found no significant difference in cardiac severity. When patients having identical mutations were compared as to their cardiac course, concordance was often not evident. Steroid therapy had no apparent protection for the development of cardiomyopathy. In conclusion, 75 patients with DMD showed marked variability in the severity of LV dysfunction. Neither age of onset nor severity of cardiomyopathy correlated with any of the mutation groups.

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Respiratory muscle strength during acute upper respiratory tract infection (URI) was assessed in patients with various forms of neuromuscular disease. Vital capacity (VC), oxygen saturation, end-tidal PCO2, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were determined in 25 stable patients with various forms of neuromuscular disease. Thirteen episodes of URI developed in 10 patients. Respiratory parameters were reassessed within 24-36 h following the onset of symptoms in each patient. In patients with URI, mean baseline VC, MIP, and MEP were 1.16 L +/- 0.14, 49.2 cm H2O +/- 6.8, and 35.5 cm H2O +/- 3.8 and fell to 1.01 L +/- 0.15, 37.1 cm H2O +/- 6.2, and 25.5 cm H2O +/- 3.0 during URI (p < 0.05 for each), respectively. Mean baseline PCO2 and oxygen saturation were 39.1 mm Hg +/- 1.1 and 95.1% +/- 1.0, and during URI, 43.9 mm Hg +/- 2.1 (p < 0.05) and 95.0% +/- 1.0 (NS), respectively. Five episodes of significant hypercapnia were observed in 4 patients. All parameters returned to near baseline values following recovery. We conclude that patients with various forms of neuromuscular disease develop reductions in respiratory muscle strength in association with URI. Unlike normal subjects, however, these decrements in respiratory muscle function may result in symptoms of shortness of breath, reductions in vital capacity, and acute hypercapnia in this patient population.

ObjectiveTo describe the natural history of cardiomyopathy in patients with Duchenne muscular dystrophy (DMD) who are receiving contemporary therapies.MethodsThis is a single-institution retrospective cohort study of 57 patients aged >15 years with DMD. Serial digital echocardiograms were performed over a median follow-up of 8 years. Left ventricular dysfunction (LVD) was defined as shortening fraction (SF) <29% plus focal wall motion abnormalities. Therapies included ACE inhibitors, beta-blockers and assisted ventilation.ResultsThe SF declined progressively in 53/57 patients (93%). LVD occurred in 40 of 57 patients (70%), with variable age at onset (median 18 years, IQR 14–21.5 years). Rate of SF decline (–1.51%±1.16%/year) was variable and unrelated to genotype. However, survival was shorter for patients with LVD onset at age <18 years vs onset at ≥18 years (death at 21.1±2.5 years vs 33.1±4.4 years; P<0.001). Death occurred in 27/57 (47%) patients at a median age of 26.3 years (IQR 20.6–31.5). Death was preceded by LVD in 22/27 patients (81%), 15 (68%) of whom developed class 4 heart failure (CHF). Time from CHF to death was brief (median 8.0 months).ConclusionDespite contemporary therapies, SF declined progressively in almost all patients. Age at onset of LVD and age at death were variable and unrelated to genotype; however, survival was shortened for patients with LVD onset at age <18 years. Death was usually preceded by LVD. CHF was a sentinel event, with death occurring shortly thereafter.

A cross sectional study was conducted on workers engaged in manufacturing precious metal powder. Of the 27 workers, 96% had raised urine silver concentrations (range 0 5-52 0 ig/l, mean 113 yg/l) and 92% had raised blood silver concentrations (range 0-05-6-2.pg/100ml, mean I 0 pg/l00 ml). Nineteen per cent also had raised urine cadmium concentrations (range 1 9-760 4ug/l, mean 11 8 jg/l). Most workers had symptoms of respiratory irritation and nose bleeds were reported in eight (30%) of the 27 workers. Deposition of silver in the cornea of the eye was detected in five of eight (63%) of the long term workers. Although not statistically significant, corneal deposition was associated with complaints of decreased night vision. The urinary enzyme N-acetyl-B-D glucosaminidase (NAG) was significantly raised in four individuals and was correlated with blood silver concentrations and age. In addition, the group's average NAG concentration was significantly higher than that found in a control population. No association between age and urinary NAG was found in the control group. Estimated creatinine clearance was also significantly lower in the group exposed to silver than in the control group. Kidney function appears to have been adversely affected by exposures at work but because of the exposure to cadmium the role of silver in causing the decrement in kidney function could not be definitely determined.There are no known acute effects of exposure to silver metal but some silver compounds such as silver oxide and silver nitrate are irritating and exposure to them has been associated with nose bleeds and abdominal pain.' With chronic exposure, silver binds to sulphydryl proteins in cells and, depending on the duration and amount of exposure, individuals may develop darkening of the conjunctiva and darkening of the skin especially in sun exposed areas. The darkening may be described as a slate grey colour. The chronic effects of silver are considered to be limited to these changes in the pigmentation of the skin and eyes without any corresponding functional defects.Silver is also deposited in the cornea of the eye. In a previous study of silver exposure extensive eye examinations to follow up complaints of decreased night vision in workers with corneal opacities from silver showed no cause for this complaint.2 Whether silver affects the kidney like other heavy metals such as mercury or cadmium has not been specifically investigated. One previous study in workers exposed to silver found limited evidence of an effect of silver on creatinine clearance.' The present study examines the chronic effects of exposure to silver, concentrating on the effects on renal function.Accepted 21 July 1986 Industrial hygiene and backgroundThe company in which the study was undertaken manufactures silver and other precious metal powder.It uses pure metals (silver bars, cadmium, gold, platinum, and paladium) as well as silver containing wastes (spent chemical catalysts) as its raw materials. Numerous chemicals including nitric acid, ...

The effects of inspiratory resistive training on respiratory muscle function was evaluated in 11 patients with Duchenne, limb-girdle, and facio-scapulo-humeral (FSH) type muscular dystrophy. Muscle training consisted of breathing against an inspiratory resistance for two 15-minute sessions each day while at home. Following 6 weeks of training, there were significant increases in the maximum resistance that could be tolerated for at least 5 minutes (P < 0.01) and also in the maximum duration that ventilations equal to 30%, 50%, 70%, and 90% of the maximum voluntary ventilation could be sustained (P < 0.05). In six patients who trained for an additional 6-week period, respiratory muscle endurance increased even further. The degree of improvement in respiratory muscle endurance was positively correlated with baseline vital capacity (r = 0.84, P < 0.05) and maximal inspiratory pressure (r = 0.76, P < 0.05). Spirometry, functional residual capacity, and maximal inspiratory and expiratory pressures were not affected by training. We conclude that inspiratory resistive training improves respiratory muscle endurance in muscular dystrophy patients. Improvement in respiratory muscle function may serve to delay the onset of respiratory complications in patients with muscular dystrophy.

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