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Biomedical subjects

R C Griggs

Publications and source records attributed to R C Griggs.

At least 127 records · Page 7Linked to original sources
PubMed1986

Effect of testosterone on whole body amino acid utilization in myotonic dystrophy.

Patients with myotonic dystrophy are markedly insulin resistant and have an associated abnormality in the regulation of arterialized amino acid concentrations during euglycemic insulin infusions. We studied the effect of testosterone treatment on whole body amino acid balance in myotonic dystrophy, since it increases muscle mass and muscle protein synthesis rate. Six patients with myotonic dystrophy underwent studies of glucose disposal and amino acid regulation during low dose insulin infusions with maintenance of euglycemia, prior to and after 10 to 13 weeks of testosterone (3 mg/kg/wk). Testosterone increased the insulin-stimulated decline of certain amino acids, but did not improve whole body glucose uptake. The anabolic effect of testosterone is separate from the anabolic effect of insulin.

Adult↗
PubMed1986

Azathioprine toxicity in neuromuscular disease.

Azathioprine toxicity was examined in 64 consecutively treated patients with various neuromuscular diseases. Reversible leukopenia was seen in 14 patients (22%). Hepatotoxicity developed in six patients (9%), and a systemic reaction characterized by fever, abdominal pain, nausea, vomiting, and anorexia occurred in eight patients (12%). Toxic effects limited the dose of azathioprine in 27 patients (42%) and led to discontinuation of therapy in 13 (20%). Macrocytosis developed in 20% of patients, but did not require an adjustment in the dose. Two patients received allopurinol and azathioprine; both developed reversible leukopenia and macrocytosis. Patients with hematologic and hepatic toxicity, but not those with systemic toxicity, successfully tolerated retreatment with azathioprine. Toxicity was delayed as long as 56 weeks after starting azathioprine in some patients.

Allopurinol↗
PubMed1986

Intermittent positive pressure breathing in patients with respiratory muscle weakness. Alterations in total respiratory system compliance.

Intermittent positive pressure ventilation (IPPB) is reported to improve lung compliance and decrease the work of breathing in subjects with kyphoscoliosis. These results suggest that IPPB may improve chest wall and lung compliance in patients with neuromuscular disease. We studied the short-term effects of IPPB on total respiratory system compliance in 14 subjects with neuromuscular disease. Seven were quadriplegics, and seven had muscular dystrophy. Vital capacity was reduced to 38 +/- 14 percent of the predicted normal values. Baseline measurements of total respiratory system compliance were 57 +/- 18 percent when compared to normal control values. After a 20 minute treatment of IPPB delivered with inspiratory pressures of 20 to 25 cm H2O that more than tripled resting tidal volume, there was no significant change in total respiratory system compliance in either group of patients. These findings indicate that patients with quadriplegia or muscular dystrophy do not derive immediate improvement in ventilatory mechanics from IPPB treatments.

Adolescent↗
PubMed1985

Lack of relationship of hypogonadism to muscle wasting in myotonic dystrophy.

Myotonic dystrophy is frequently associated with testicular atrophy. Since androgens may play a role in the maintenance of muscle mass, we have studied the levels of plasma testosterone and gonadotropins and of urinary 17-ketosteroids in 22 men with myotonic dystrophy, 36 normal men, and 16 men (control group) with muscle wasting. Results were correlated with muscle mass as estimated by creatinine excretion and total body potassium. Patients with myotonic dystrophy had significantly lower testosterone and higher gonadotropin levels than normal, and these changes were progressive in longitudinal studies. Testosterone levels were also lower than normal in disease control subjects. There was no correlation between low testosterone levels and diminished muscle mass in either myotonic dystrophy or disease control patients. The low plasma concentration of testosterone in men with myotonic dystrophy and other neuromuscular diseases does not appear to be directly related to their muscle wasting. This study does not exclude the possibility that an alteration in testosterone receptor or tissue effects may contribute to a loss of muscle tissue.

17-Ketosteroids↗
PubMed1985

Severe neonatal centronuclear myopathy with autosomal dominant inheritance.

We studied a boy with severe infantile centronuclear myopathy (CNM) and his mother with clinical, electrophysiological, and pathological signs of skeletal muscle, peripheral nerve, and brain-stem disorder, and we believe that her condition represents a variation of her son's disease. His brother had similar symptoms and died at 4 days of age. The occurrence of this syndrome in a symptomatic mother and two severely affected sons suggests an autosomal dominant inheritance with variable expressivity. To our knowledge, this inheritance pattern has not been previously reported in severe (fatal) infantile CNM. The different courses in the mother and her offspring may be manifestations of a single or separate abnormal gene causing alteration of muscle and nerve maturation.

Child↗
PubMed1985

In vivo estimation of muscle protein synthesis in myotonic dystrophy.

The rate of muscle protein synthesis in patients with myotonic dystrophy has been studied, and results correlated with total muscle mass. Whole body and skeletal muscle protein synthesis were estimated by stable isotope methodology with a primed, continuous infusion of 1-[13C]leucine with measurement of incorporation of [13C]leucine into muscle protein in biopsy samples. Whole body leucine flux, protein synthesis, and protein breakdown were only slightly depressed, but muscle protein synthesis was markedly decreased, in myotonic dystrophy. This depression of muscle protein synthesis in myotonic dystrophy correlates with previous observations of impaired insulin-induced muscle uptake of amino acids and supports the suggestion that muscle wasting in this disease is the consequence of defective anabolism in muscle.

Adolescent↗
PubMed1985

Polyneuropathy and IgM monoclonal gammopathy: studies on the pathogenetic role of anti-myelin-associated glycoprotein antibody.

Attention has recently been directed toward patients having a polyneuropathy and a monoclonal IgM anti-myelin-associated glycoprotein (anti-MAG) antibody. The possibility of a pathogenetic role for the anti-MAG antibody in the evolution of the polyneuropathy and in the development of central nervous system signs, including tremor and ataxia, remains unresolved. In 5 patients with this syndrome whose clinical courses were followed closely, in 1 of whom a complete postmortem examination of the nervous system was performed, we made the following observations: the anti-MAG antibody did not localize to the compact layer of the myelin sheath in affected nerves, but did localize to areas of myelin splitting; anti-MAG antibody present in the sural nerve of an affected individual for 7 years was not associated with progressive pathology; anti-MAG antibody was not deposited in the central nervous system of an affected individual, although the antibody did bind to these same tissues in vitro; deposition of anti-MAG antibody observed at postmortem examination did not correlate with the degree of pathological change; and study of the peripheral nervous system favored a primary axonal neuropathy with secondary demyelination.

Adult↗
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

Abnormal regulation of venous alanine after glucose ingestion in myotonic dystrophy.

The concentration of amino acids in whole blood was measured before and during standard 5 h oral glucose tolerance testing in six male patients with myotonic dystrophy and five normal males. The plasma levels of insulin and glucose were also determined. From 90 to 240 min after glucose ingestion there was a striking decline in venous alanine concentration in the patients with myotonic dystrophy in contrast to a slight rise in alanine in the normal group. The patients displayed normal glucose tolerance, and there was a sustained fall in the venous concentration of the insulin-sensitive amino acids comparable with that seen in the normal controls. However, the patients showed a threefold increase of plasma insulin after glucose. These data indicate an abnormal regulation of alanine in myotonic dystrophy which may be the result of an alteration in muscle synthesis of this amino acid. This defect in alanine synthesis may be due to a decreased availability of intracellular pyruvate caused by the insulin resistance that exists in these patients.

Adult↗
PubMed1985

Myotonic dystrophy: effect of testosterone on total body potassium and on creatinine excretion.

Muscle wasting in myotonic dystrophy appears to reflect impaired anabolism rather than accelerated catabolism. We therefore investigated the effects of testosterone, an anabolic hormone, on muscle mass as estimated by creatinine excretion and total body potassium in nine patients with myotonic dystrophy. Weekly injections of testosterone for 10 to 13 weeks increased both creatinine excretion (19%) and total body potassium (16%) in all patients. Metabolic balance data showed a confirmatory accretion of nitrogen, potassium, and phosphorus. Because testosterone increases indirect measures of muscle mass, it may deserve a therapeutic trial in myotonic dystrophy.

Adult↗
PubMed1984

Dissociation of glucose and potassium arterial-venous differences across the forearm by acetazolamide. A possible relationship to acetazolamide's beneficial effect in hypokalemic periodic paralysis.

We studied the effect of acetazolamide on arterial-venous (A-V) glucose and potassium differences across the forearm following oral glucose loading in eight normal subjects. Administration of acetazolamide for 72 hours prior to glucose loading resulted in increased A-V glucose differences and decreased A-V potassium differences. Acetazolamide may, therefore, increase glucose uptake across muscle while decreasing potassium uptake following glucose ingestion. This glucose-potassium dissociation observed in normal subjects may relate to acetazolamide's beneficial effect in hypokalemic periodic paralysis.

Acetazolamide↗
PubMed1984

Effect of acetazolamide on insulin sensitivity in myotonic disorders.

Acetazolamide is effective treatment for myotonia in certain patients with myotonia congenita. Since potassium metabolism may be abnormal in myotonia congenita, we studied the effect of acetazolamide administration on potassium regulation and glucose disposal, using the euglycemic insulin clamp technique in patients with myotonic disorders and in normal subjects. Glucose disposal was normal in patients with myotonia congenita; administration of acetazolamide increased glucose disposal in normal subjects and in patients with myotonia congenita. By contrast, patients with myotonic dystrophy showed insulin resistance and decreased glucose disposal that was not improved by acetazolamide administration. Patients with myotonia congenita had elevated potassium levels in the basal state and a greater fall in potassium level during the insulin clamp procedure than controls. Patients with myotonic dystrophy had normal or low basal potassium levels and a subnormal decrease in potassium level during the insulin clamp procedure. Administration of acetazolamide did not alter these abnormalities in potassium metabolism in patients with either myotonia congenita or myotonic dystrophy.

Acetazolamide↗
PubMed1984

Preparation of CO2 from blood and protein-bound amino acid carboxyl groups for quantification and 13C-isotope measurements.

Measurements of protein and amino acid metabolism in man using stable isotopes and selected ion monitoring gas chromatographic/mass spectrometric techniques are limited by the requirement of relatively high levels of labelling for adequate precision (greater than 0.05 at % excess). We describe here a means of extending the scope of such studies by measurement of lower levels of enrichment achieved in gaseous CO2 derived from whole blood or protein-bound amino acids following the administration of tracer amounts of appropriately labelled substrates. Construction and operation of a novel glass vacuum line required for this work are described in detail and specific applications relevant to clinical investigations are outlined. Measurements of both the total amount of CO2 and its 13C enrichment are performed in an isotope-ratio mass spectrometer which provides acceptable levels of accuracy and reproducibility for both measurements (+/- 0.1% and +/- 0.0001 at % excess respectively).

Amino Acids↗
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

Cyanotic congenital heart disease with suspected stroke. Should all patients receive antibiotics?

Two patients with cyanotic congenital heart disease (CHD) and erythremia were seen for abrupt onset of focal neurologic deficits and/or seizure without signs of infection or increased intracranial pressure. Clinical features and initial computed tomography (CT) in both cases suggested stroke. Subsequent CT scans demonstrated cerebral abscess, proved at operation. Review of records of patients with CHD at the University of Rochester (NY) Medical Center from 1965 to 1981 disclosed 12 cases with brain abscess but only two cases with aseptic cerebral infarction. All but one patient with abscess were cyanotic. One third of patients with abscess had a clinical picture suggesting stroke. Clinical or radiologic features of half the cases indicated that cerebral infarction may have led to abscess formation. Diagnosis of brain abscess and immediate antibiotic therapy should be strongly considered in patients with cyanotic CHD who suffer a suspected cerebral infarction.

Adult↗