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Biomedical subjects

M H Brooke

Publications and source records attributed to M H Brooke.

At least 37 records · Page 2Linked to original sources
PubMed1990

Randomized, double-blind trial of mazindol in Duchenne dystrophy.

There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.

Behavior↗
PubMed1990

Fatigue testing.

Explore the source record for details and available documents.

Biomechanical Phenomena↗
PubMed1989

Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy.

We performed a randomized, double-blind, controlled six-month trial of prednisone in 103 boys with Duchenne's muscular dystrophy (age, 5 to 15 years). The patients were assigned to one of three regimens: prednisone, 0.75 mg per kilogram of body weight per day (n = 33); prednisone, 1.5 mg per kilogram per day (n = 34); or placebo (n = 36). The groups were initially comparable in all measures of muscle function. Both prednisone groups had significant improvement of similar degree in the summary scores of muscle strength and function. Improvement began as early as one month and peaked by three months. At six months the high-dose prednisone group, as compared with the placebo group, had improvement in the time needed to rise from a supine to a standing position (3.4 vs. 6.2 seconds), to walk 9 m (7.0 vs. 9.7 seconds), and to climb four stairs (4.0 vs. 7.1 seconds), in lifting a weight (2.1 vs. 1.2 kg), and in forced vital capacity (1.7 vs. 1.5 liters) (P less than 0.001 for all comparisons). There was an increase in urinary creatinine excretion (261 vs. 190 mg per 24 hours), which suggested an increase in total muscle mass. However, the prednisone-treated patients who had required long-leg braces (n = 5) or wheelchairs (n = 11) continued to require them. The most frequent side effects were weight gain, cushingoid appearance, and excessive hair growth. We conclude from this six-month study that prednisone improves the strength and function of patients with Duchenne's muscular dystrophy. However, further research is required to identify the mechanisms responsible for these improvements and to determine whether prolonged treatment with corticosteroids may be warranted despite their side effects.

Adolescent↗
PubMed1989

Thyrotropin-releasing hormone in ALS. Are the results of clinical studies inconsistent?

The results of the various studies and an analysis of the methodology are presented in TABLE 1. As can be seen, there was no "perfect" study. In five of the studies enough information was presented with regard to the measurements and the behavior of control patients that a statistical analysis could be performed. Three of the studies showed a transient, statistically significant effect in at least some muscles. The two studies that demonstrated no such effect both used TRH in very small doses. It therefore seems reasonable to conclude that the effect of TRH in ALS is a definite, acute, and transient response. The cause of this response, however, has not been documented, and whether it is associated with an effect of the drug on the disease process remains to be seen.

Amyotrophic Lateral Sclerosis↗
PubMed1989

Two dissimilar brothers with Becker's dystrophy have an identical genetic defect.

Becker's muscular dystrophy is phenotypically heterogeneous, but the clinical expression is usually similar in patients within the same family. We report here 2 brothers affected with Becker's muscular dystrophy in whom the disease followed completely different courses. The disease started in both patients before their teens. However, the oldest sibling died at 37, following many years of severe disability, whereas the other sibling, now 26, has normal muscle strength. In addition, since the age of 13, the younger brother has had epilepsy and has been treated with phenytoin combined with other antiepileptic drugs. Analysis of the DNA from each of the 2 brothers revealed a similar deletion at the 5' end of the dystrophin gene. The different clinical courses despite the similar mutational event suggest that intrinsic muscle factors due to modified genes or environmental phenomena such as prolonged treatment with phenytoin or other antiepileptic agents may have influenced the clinical course.

Adult↗
PubMed1989

Randomized controlled trial of testosterone in myotonic dystrophy.

Because testosterone has an anabolic effect in myotonic dystrophy, we conducted a 12-month, randomized, double-blind therapeutic trial of testosterone enanthate (3 mg/kg/wk) in 40 men with myotonic dystrophy. We evaluated strength by manual muscle tests, quantitative myometry, pulmonary function, and quantitative functional assessment. A sustained, significant elevation of testosterone levels was produced but there was no effect on any measurement of muscle strength. Muscle mass as estimated by creatinine excretion and lean body mass (40K method) increased significantly. We conclude that testosterone does not improve strength in myotonic dystrophy despite increasing muscle mass.

Acne Vulgaris↗
PubMed1989

Genetic abnormalities in Duchenne and Becker dystrophies: clinical correlations.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are two allelic forms of an X-linked muscle disorder exhibiting phenotypic heterogeneity. We studied 49 individuals clinically diagnosed as having classic DMD, female DMD, mild DMD "outliers," and BMD. The patients' DNA was analyzed and alterations detected were correlated with particular phenotypes. We found that 14 of 32 classic DMD patients have an internal deletion in the same, relatively small, region of the gene; therefore this region may undergo deletions at a higher rate than the remainder of the gene. We could detect no alterations in the DNA in the remaining 18 patients. Selected patients from both groups failed to show muscle dystrophin. Seven of 11 patients with a mild DMD or BMD phenotype showed deletions at the 5' end of the gene. The other 4 patients failed to show deletions. Three of the patients with both a mild phenotype and a deletion at the 5' end had normal or low amounts of a dystrophin of smaller molecular weight. Patients with classic DMD who had a detectable deletion had a milder clinical course than those without. Contrary to a previous report, no patient in the population of clinically precisely defined DMD boys showed a deletion at the 5' end; thus, the outlier and BMD patients may be genetically different from boys with classic DMD. This correlation may be of diagnostic and prognostic significance.

Adolescent↗
PubMed1989

Duchenne muscular dystrophy: patterns of clinical progression and effects of supportive therapy.

Two-hundred eighty-three boys with Duchenne dystrophy and 10 with Becker dystrophy have been followed for up to 10 years in a protocol that accurately measured their function, strength, contractures, and back curvature. Clinical heterogeneity is noted. Patients whose muscles were stronger were more likely to die from a cardiomyopathy. Weaker patients died from respiratory failure. A series of milestones is defined, which is of use in following the illness in an individual patient. This approach permits a scoring system that allows the severity of the disease to be defined in an individual boy. Evaluation of physical therapy and surgical intervention shows that night splints and scoliosis surgery are effective forms of treatment.

Cardiomyopathies↗
PubMed1988

Clinical investigation in Duchenne muscular dystrophy: penicillamine and vitamin E.

A double-blind controlled trial of penicillamine and vitamin E against placebo was conducted in 106 boys with Duchenne muscular dystrophy. Nine dropped out of the study after being randomized. Patients were evaluated using an established protocol that measures muscle strength, joint contractures, functional grade, and pulmonary function. The trial lasted for 18 months. The power of the study to detect a 75% slowing of the disease was 0.95 at a P less than 0.05. No therapeutic effect was observed in the patients taking penicillamine and vitamin E as compared with those taking placebo.

Child↗
PubMed1988

2,4-Dinitrophenol, muscle biopsy, and McArdle's disease.

Exercise is simulated in muscle biopsy preparations by using low concentrations of 2,4-dinitrophenol (DNP), which do not produce contracture or anatomic damage. The validity of this simulation is supported by (1) the biochemical effects of simultaneous muscle contraction and DNP are not additive, suggesting that exercise and DNP stress the same pathways; (2) the effects of increasing concentrations of DNP and increasing levels of stimulation are similar with an early drop in phosphocreatine, increasing lactate and inosine monophosphate (IMP), and a late fall in ATP levels; and (3) DNP provocation in a patient with McArdle's disease demonstrated an absence of lactate and high levels of IMP correlating with clinical findings. DNP provocation may be a simple way of studying metabolic pathways in neuromuscular diseases.

2,4-Dinitrophenol↗
PubMed1987

Clinical investigation of Duchenne muscular dystrophy. A methodology for therapeutic trials based on natural history controls.

Between 1979 and 1987 we documented the natural history of Duchenne muscular dystrophy in 170 patients, aged from 3 to 23 years, by making serial measurements in over 5000 individual evaluations. This database makes it possible to design and conduct therapeutic trials using natural history controls. Such trials do not replace the need for randomized placebo-controlled trials of promising agents but they do require fewer patients, are cost-effective, and permit the use of high-risk therapy where toxicity monitoring may be important. Natural history-controlled trials, therefore, may serve as a screening method for new therapeutic agents. Drugs showing a significant benefit can then be evaluated in a randomized controlled trial.

Adolescent↗
PubMed1987

Clinical investigation of Duchenne muscular dystrophy. Interesting results in a trial of prednisone.

We investigated the effect of high-dose prednisone therapy in 33 boys with Duchenne muscular dystrophy. The drug was given daily in doses of 1.5 mg/kg of body weight (to a maximum of 80 mg) for six months. Muscle strength, joint contractures, timed functional tests, functional ability, and pulmonary function were measured at the beginning and end of the treatment period. The trial was designed using natural history controls, and the power of the study was 0.80 to detect a slowing of 50% in the rate of progression. During the period of the trial, muscle strength, functional grades, timed functional tests, and pulmonary function improved. Contractures followed the expected natural history of the illness.

Adolescent↗
PubMed1987

Genetic heterogeneity in Duchenne dystrophy.

We evaluated 173 patients in the Clinical Investigation of Duchenne Dystrophy study to determine if patients from the same kindred were more alike clinically than patients within the study population as a whole. A high intrafamilial correlation was noted for age-adjusted muscle strength scores. While noninherited factors could, in part, explain the results, it seems likely that genetic heterogeneity may contribute to the observed similarity within Duchenne dystrophy kindreds.

Adolescent↗
PubMed1987

Clinical investigation in Duchenne dystrophy. VI. Double-blind controlled trial of nifedipine.

Excessive accumulation of intracellular calcium in Duchenne muscular dystrophy (DMD) may be a necessary step in the process that causes muscle damage in this disease. Because of this possibility, a controlled trial of the calcium channel blocking agent nifedipine was undertaken. One hundred and five patients were randomized and treated in a double-blind manner for 18 months. Muscle strength, contractures, functional ability, cardiopulmonary changes, and laboratory data were monitored. The dose of nifedipine was 0.75-1 mg/kg/day in the first 6 months and 1.5-2 mg/kg/day for the next 12 months. Satisfactory blood levels of nifedipine were attained. The study had a power greater than 0.99 to detect a slowing of the illness to 25% of its original rate of progression. No significant improvement was demonstrated in the treated group. One or more of the frequent mild side effects of flushing, dizziness, and leg edema, often associated with the use of nifedipine in adults, occurred transiently in approximately one-half of the patients in the nifedipine group and in 21% of the placebo group. Four patients died, two on nifedipine and two on placebo. This study demonstrates that nifedipine is safe to administer in children, but that it is without beneficial effect on the course of DMD.

Adolescent↗
PubMed1987

Use of serum creatine kinase, pyruvate kinase, and genetic linkage for carrier detection in Duchenne and Becker dystrophy.

Carrier detection in Duchenne dystrophy (DD) and Becker dystrophy (BD) can be achieved with DNA probes that recognize restriction fragment length polymorphisms (RFLPs). In 22 families, we found that 16 of 23 females at risk for being DD or BD carriers could be provided with more definitive indications of carrier status beyond the use of creatine kinase/pyruvate kinase and pedigree analysis. RFLP analysis was not possible for six individuals despite potentially informative probes, because family members critical to the analysis were unavailable. In only one instance were all eight probes uninformative.

Creatine Kinase↗