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Biomedical subjects

M H Brooke

Publications and source records attributed to M H Brooke.

At least 55 records · Page 3Linked to original sources
PubMed1987

McArdle's disease with myoadenylate deaminase deficiency: observations in a combined enzyme deficiency.

Exercise and work potential of a patient with coexistent myophosphorylase and myoadenylate deaminase (AMPDA) deficiency was compared with that of three patients with myophosphorylase deficiency alone. The patient with the combined defect failed to produce an abnormal rise in serum ammonia or hypoxanthine as seen in the other patients after forearm exercise. Maximum oxygen consumption and work rates during cycle ergometer testing were similar in all patients, but well below controls. The occurrence of two defects involving short-term energy metabolism in muscle presents an opportunity to define further the metabolic role of AMPDA.

AMP Deaminase↗
PubMed1987

Carrier assessment for mothers and sisters of isolated Duchenne dystrophy cases: the importance of serum enzyme determinations.

DNA studies (restriction fragment length polymorphism linkage analysis and deletion analysis with pERT87) and serum creatine kinase/pyruvate kinase (CK/PK) measurements were done to determine the carrier status of 59 mothers and sisters of isolated Duchenne dystrophy (DD) cases. The results of DNA studies modified the carrier risks for 34 of the 59 (58%), but the derived risks often did not differ importantly from risks calculated by conventional methods. Elevated CK/PK provided strong evidence of the carrier state for 24 of the 59 (41%), and CK/PK frequently provided data unavailable through DNA studies. Serum enzyme determinations remain an important means of evaluating DD carrier suspects and are especially valuable in isolated-case families. Enzyme testing should be combined with DNA studies to achieve the best estimate of carrier risk.

Creatine Kinase↗
PubMed1986

'Dystrophic' lipid myopathy in two sisters.

Two sisters with progressive myopathy demonstrated microscopic and biochemical evidence of lipid storage in skeletal muscle. Their muscle biopsy specimens resembled those seen in Duchenne's muscular dystrophy and some of the biochemical features were similar, including increased muscle concentration of long-chain acyl-coenzyme A (a fatty oxidation intermediate) and decreased oxidation of radioactively labeled fatty acids by muscle homogenates in vitro. Although the site of the defect was not localized, the data suggested impairment of intramitochondrial beta-oxidation of fatty acids. These two patients may be important in understanding the pathogenesis of muscular dystrophy.

Child↗
PubMed1986

Controlled trial of thyrotropin releasing hormone in amyotrophic lateral sclerosis.

A double-blind controlled trial of thyrotropin releasing hormone (TRH) 150 mg IM daily in 30 patients with amyotrophic lateral sclerosis is reported. The drug/placebo was administered for 2 months, followed by a 2-month "wash-out". Evaluation of strength, functional ability, and respiratory functions was performed. A temporary increase in the strength of some muscles was detected following the administration of TRH, but no change in functional performance was noted. Neither the patients nor the investigators believed the effects were of any marked clinical significance. The course of the illness was not altered.

Adult↗
PubMed1986

Inosine monophosphate production is proportional to muscle force in vitro.

An in vitro system of muscle stimulation has been developed that combines physiologic measurements with biochemical evaluation. In the rat epitrochlearis muscle, 2 minutes of stimulation at 4 Hz results in a marked elevation of inosine monophosphate (IMP) levels. The amount of IMP generated is proportional to the amount of force developed. Depriving the muscle of oxygen results in an increased amount of IMP generation. This model provides direct confirmation of similar findings in the human forearm exercise test.

Adenosine Diphosphate↗
PubMed1985

Clinical investigation in Duchenne dystrophy: V. Use of creatine kinase and pyruvate kinase in carrier detection.

We have determined the value of creatine and pyruvate kinase (CK and PK) in carrier detection by evaluating 811 females in 73 families participating in the Collaborative Investigation of Duchenne Dystrophy. Thirty-nine obligate carriers, 244 normal controls (paternal females), as well as 76 possible carriers and 351 carrier suspects had three CK and PK specimens analyzed at a central laboratory. The CK and PK values varied with age in normals: both fell with age early in life, and CK rose after the fifth decade. Discriminant analysis indicated that the combination of mean CK and PK corrected for age yielded the best data for calculation of carrier probability. Using the best model, only 45% of obligate carriers could be identified at a false-positive rate of 2.5%. Daughters of obligate carriers have a disproportionate decline in CK and PK with age as compared to noncarrier females, suggesting that the rate of carrier detection will be higher in the first two decades. Our low rate of carrier detection, as compared to other studies, may reflect both the age of our obligate carrier population and the use of a control group that is more representative of the carrier population.

Adolescent↗
PubMed1985

Activity, creatine kinase, and myoglobin in Duchenne muscular dystrophy: a clue to etiology?

Large and seemingly random fluctuations in the serum levels of creatine kinase (CK) and myoglobin (Mb) have been noted in patients with Duchenne muscular dystrophy. We studied seven affected boys, aged 2 to 9 years. Blood was drawn for CK and Mb every 4 hours, and the boys' activity was documented hourly for 4 days. There was a close correlation between serum levels of CK and Mb with physical activity. Fluctuations in serum levels of CK and Mb are not random and may result from an abnormality of fatty acid metabolism.

Child↗
PubMed1984

Clinical investigation in Duchenne muscular dystrophy: IV. Double-blind controlled trial of leucine.

Ninety-six patients with Duchenne muscular dystrophy (DMD) were randomized and placed either on placebo or oral leucine at a dose of 0.2 g per kg per day. Patients were evaluated using a protocol that measured muscle strength, joint contracture, functional grade and activity, and pulmonary function tests. After 1 month there was a transient but significant difference in the strength of the two groups, the treated group being stronger than the placebo group. At 6 months there was also a transient difference in joint contracture measurements. Analysis of the data showed that the difference between the groups for both these measurements could not be ascribed to a therapeutic effect of leucine but rather to an unexpected drop in the placebo group. This was recognized only because the slope of deterioration for these functions had been well documented during the natural history phase of the study. These results indicate that oral leucine failed to produce a therapeutic response over a 1-year double-blind, controlled trial.

Child↗
PubMed1983

Clinical investigation in Duchenne dystrophy: 2. Determination of the "power" of therapeutic trials based on the natural history.

A prospective study of 114 patients with DMD provided data for "power" calculations for future therapeutic trials. There was a decline in strength of 0.4 units per year (on a 0-10 scale). Contractures of the iliotibial bands, hip flexors, and heel cords developed before 6 years. Contractures of other joints accompanied the increased use of wheelchairs. All children walked until 8 years with functional "improvement" between 3-6 years. Children of the same age varied widely in their strength, degree of contracture, and functional abilities. Fifteen percent of the patients appear to have a milder variety of the disease and are termed "outliers." To test a drug which might slow the disease to 25% of its original rate of progression, two groups (placebo and treatment) of 40 patients each would have to be followed for one year.

Adolescent↗
PubMed1983

Increased long chain acyl CoA in Duchenne muscular dystrophy.

Compared with normal or denervated human muscle, long chain acyl CoA was increased in muscle from patients with Duchenne dystrophy. Free and short chain acylcarnitine were reduced in Duchenne muscle, whereas long chain acylcarnitine was preserved. The accumulation of long chain fatty acid derivatives may imply disruption of fatty acid oxidation.

Acyl Coenzyme A↗
PubMed1983

Exercising muscle does not produce hypoxanthine in adenylate deaminase deficiency.

The failure of forearm exercise to increase plasma hypoxanthine in subjects with adenylate deaminase deficiency confirms this enzyme's role in hypoxanthine production by normal forearm exercise. The conversion of adenosine monophosphate (AMP) to hypoxanthine may reflect an alternative method of adenosine triphosphate (ATP) regeneration in working muscle.

AMP Deaminase↗
PubMed1982

Incomplete palmitate oxidation. Possible source of human myopathy.

A study of palmitate oxidation in 200 consecutive human muscle biopsy specimens showed 14 patients in whom there was abnormal, incomplete palmitate oxidation when the rate of oxidation of palmitate 14C (ul) was compared with that of palmitate 14C (at carbon 1). Five patients had denervation as a primary diagnosis, and the remaining nine had a primary muscle disease. Of this latter group, six had clinical similarities, including proximal weakness, necrotic fibers on muscle biopsy, and extreme elevations of serum creatine kinase. With one exception, lipid storage was not part of the syndrome. The possibility of incomplete palmitate oxidation due to a defect in beta-oxidation producing a human myopathy is discussed.

Adolescent↗
PubMed1982

Palmitate oxidation in human muscle: comparison to CPT and carnitine.

The evaluating of palmitate oxidation in muscle tissue may be a useful screening test for detecting defects in fatty acid metabolism in human neuromuscular disease. If the test is to be useful, it is necessary to obtain data on a wide variety of muscle illnesses for comparative purposes. We report our experience with palmitate oxidation, muscle carnitine, and carnitine palmityl transferase (CPT) activity in 148 muscles biopsies from a variety of illnesses. The efficacy of using total protein, citrate synthase, and (1-14C) pyruvate oxidation as internal references was investigated. Palmitate oxidation was significantly less than normal (P less than or equal to 0.01) in Duchenne muscular dystrophy, congenital nonprogressive myopathy, congenital muscular dystrophy, malignant hyperpyrexia, and denervation, depending on the internal reference used. Muscle carnitine levels followed a similar pattern, however, CPT activity did not. The possibility of these findings being secondary to inactivity is discussed.

Acyltransferases↗
PubMed1982

Forearm exercise increases plasma hypoxanthine.

Plasma hypoxanthine was measured in three normal subjects during aerobic forearm exercise. The comparative increase of hypoxanthine greatly exceeded that of ammonia or lactate. It is proposed that hypoxanthine production reflects ATP breakdown in muscle. The test may prove useful in the investigation of patients with metabolic muscle disease.

Adenosine Triphosphate↗
PubMed1982

Exercise hyperventilation in patients with McArdle's disease.

This study was undertaken to determine if patients who lack muscle phosphorylase (i.e., McArdle's disease), and therefore the ability to produce lactic acid during exercise, demonstrate a normal hyperventilatory response during progressive incremental exercise. As expected these patients did not increase their blood lactate above resting levels, whereas the blood lactate levels of normal subjects increased 8- to 10-fold during maximal exercise. The venous pH of the normal subjects decreased markedly during exercise that resulted in hyperventilation. The patients demonstrated a distinct increase in ventilation with respect to O2 consumption similar to that seen in normal individuals during submaximal exercise. However their hyperventilation resulted in an increase in pH because there was no underlying metabolic acidosis. End-tidal partial pressures of O2 and CO2 also reflected a distinct hyperventilation in both groups at approximately 70-85% maximal O2 consumption. These data show that hyperventilation occurs during intense exercise, even when there is no increase in plasma [H+]. Since arterial CO2 levels were decreasing and O2 levels were increasing during the hyperventilation, it is possible that nonhumoral stimuli originating in the active muscles or in the brain elicit the hyperventilation observed during intense exercise.

Adult↗