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Biomedical subjects

R A Kark

Publications and source records attributed to R A Kark.

29 records · Page 2Linked to original sources
PubMed1977

Physostigmine in familial ataxias.

Physostigmine was given to 12 patients with various spincerebellar degenerations, and neurologic examinations were recorded on video tapes and assessed on a semiquantitative scale. Forty minutes after a single dose, the scores improved by 35.7 +/- 4.7 percent (means +/- SEM). Eight patients were then studied over sequential 3-month periods by a randomized double-blind trial of physostigmine versus placebo. With physostigmine, scores were 33.9 +/- 8.3 percent better than before treatment or with placebo. Further investigations of cholinergic drugs seem warranted in patients with these diseases.

Ataxia↗
PubMed1976

Low activities of the pyruvate and oxoglutarate dehydrogenase complexes in five patients with Friedreich's ataxia.

Since patients with Friedreich's ataxia appear to oxidize pyruvate slowly, we measured the activity of the pyruvate dehydrogenase complex in disrupted fibroblasts from four patients with this syndrome and one patient with a clinical variant. The activity was 43 +/- 4 per cent of that in 16 controls (mean +/- S.E.M., P less than 0.001). The activity of the 2-oxoglutarate dehydrogenase complex was also lower in the patients' cells than in those of controls (50 +/- 2 per cent, P less than 0.001). However, the activity of cytochrome-c oxidase was normal (126 +/- 43 per cent of controls). Mixing experiments gave no evidence of soluble enzyme inhibitors or activators, and the addition of excess substrate or cofactor did not ameliorate the deficiencies. White blood cells from one of the patients had low activities of both complexes. Mutations of these dehydrogenase complexes occur in some patients with Friedreich's ataxia and lead to abnormally low activity of an enzyme of the tricarboxylic acid cycle.

Adolescent↗
PubMed1976

Ketonic diet in the management of pyruvate dehydrogenase deficiency.

Two brothers, aged 11 years 6 months and 2 years 3 months, with psychomotor and growth retardation, episodes of weakness, ataxia, ophthalmoplegia, and elevated levels of blood pyruvate were shown to have a deficiency in the pyruvate dehydrogenase complex (PDH). When they ate a diet high enough in fats to cause ketonemia but not acidosis, there was a fall in blood pyruvate levels, a decrease in the frequency and severity of the episodes of neurological deterioration, an increased rate of growth and development in the younger brother, and increased strength and endurance in the older one. The possibility of dietary treatment makes the early diagnosis of PDH deficiency more important. Determination of blood pyruvate and lactate levels following a standard glucose meal (glucose-pyruvate test) appears to be the most reliable screening test for this condition.

Alanine↗
PubMed1975

Experimental thiamine deficiency. Neuropathic and mitochondrial changes induced in rat muscle.

Whether pure thiamine deficiency produces a neuropathy in Mammalia is still debated. Rats were pair-fed-synthetic diets with and without thiamine. When studied histochemically, soleus muscles from thiamine-deficient rats showed (1) small, angular fibers that had high NADH dehydrogenase activities; (2) a loss of 43% of type II (FOG) fibers; (3) decreased intensity of the reaction for betaOHB dehydrogenase; and (4) fibers with subsarcolemmal collections resembling "ragged-red" muscle. Electron microscopy revealed degeneration of some small myelin sheaths of distal and intramuscular nerves; atrophic, degenerating, hypoosmophilic muscle fibers in soleus and vastus medialis; and scattered muscle fibers with abnormal collections of deranged mitochondria accompanied by lipid droplets. These abnormalities, not found in control muscles, indicate that both motor neuropathy and mild mitochondrial changes, such as are seen in the "ragged-red" diseases, are induced by pure thiamine deficiency.

Adenosine Triphosphatases↗
PubMed1971

Heredopathia atactica polyneuritiformis (Refsum's Disease): a second trial of dietary therapy in two patients.

Two sibs with heredopathia atactica polyneuritiformis (Refsum's Disease) each had a relapse after ceasing to follow a special diet. On being placed on a very restricted low phytol, low phytanic acid diet both had marked subjective improvement, and marked objective improvement both in physical findings and in quantitative tests of strength, dexterity, and motor nerve conduction velocities, concomitant with a fall in serum phytanic acid levels. No relapse occurred in 22 months on this diet.

Ataxia↗
PubMedDate not supplied

Multiple genotypes, multiple phenotypes, and partial defects.

In recent years, the following ideas have been expressed: (a) that all cases of a discrete, inherited neuromuscular syndrome should prove to be due to a single biochemical defect, (b) that any single biochemical defect should give rise only to one syndrome, and (c) that an enzymatic defect cannot give rise to a disease unless there is virtual absence of activity, that is, less than 5% or 10% of the normal value. We review evidence from research in neuromuscular, neurological, and other genetic diseases of humans that suggest the contrary. There are now examples of single clinical syndromes related to each of several defects, of defects of one biochemical reaction related to two or more distinct clinical syndromes, and of partial defects associated with disease in a way that suggests a causal relationship.

Anemia, Hemolytic, Congenital↗