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The pharmacokinetics of primaquine (PQ) and its major carboxylic acid metabolite (PQC) have been studied in seven Indian patients with P. vivax malaria following PQ 15 mg/day p.o. for 14 days. After a single oral dose on Day 1, a mean peak blood concentration of 50.7 ng/ml PQ was attained after 2.3 h, which declined monoexponentially with a half-life of 5.6 h. The mean total body clearance was 37.6 l/h and the volume of distribution was 2921. The mean renal excretion (0-24 h) of the drug was only 0.54% of the dose and renal clearance was 0.189 l/h. Following chronic administration, none of the pharmacokinetic parameters was affected, and a steady state blood concentration of 2.5-4.2 ng/ml PQ was attained. After the first dose of PQ, PQC had a mean area under the blood concentration - time curve 11-fold higher than that of the parent drug. In contrast to the rapid distribution and elimination of PQ, the metabolite showed a longer mean residence time and accumulation in the body. The mean C and AUC of the metabolite on Day 14 were 48 and 40% higher than the corresponding Day 1 values. The metabolite could not be detected in urine at any time in any patient. PQ and its metabolite did not show any accumulation in blood cells. [ABSTRACT FROM AUTHOR]

A clinical and electrophysiological study of 15 cases of cephalic tetanus is reported. This condition is a form of local tetanus which commonly follows an injury to the face or head. It is characterised by muscle paralysis which is maximal close to the site of injury, while spasm is evident at mroe distant sites. As muscle paralysis improves with time it is succeeded by spasm. It is argued that paralysis is due to high local concentrations of toxin in the brainstem while lesser concentrations cause spasm by abolishing inhibition. Electrophysiological studies indicate that paralysis is of lower motor neurone type with denervation potentials, hyperirritability, loss of motor units, and marginally increased distal latencies being the features recorded. [ABSTRACT FROM AUTHOR]

Pathological findings are reported on 34 specimens from 16 cases of arthrogryposis multiplex congenita (AMC), including initial observations on paraffin sections from 28 muscles, and subsequent observations on six additional specimens from three of these cases studied both histologically and histochemically. Thirteen of the 34 specimens (from 11 cases) were histologically normal, probably on account of an unaffected muscle being sampled. The most constant pathological feature in the remaining specimens was a disorganization of the muscle fibres and fascicles by severe fibrosis; only three specimens (from two cases) did not show this. Very thin faintly striated muscle fibres embedded in this matrix were encountered in 10 specimens from nine cases. An attempt at grouping of these atrophic or ill-developed fibres was noticed in four specimens; but this may not be denervation atrophy. Two specimens (from two cases) showed `myopathic' features. Repeat biopsy after two to three years was carried out on two affected muscles each from three patients. Case 3 showed well preserved but uniformly small fibres. Case 4 showed extremely few and scattered small rounded fibres. Case 14 showed pronounced variation of fibre size in both, with both atrophic and hypertrophied fibres. Normal nerves and spindles were seen in all these six specimens irrespective of the state of the muscle, and excessive fibro-fatty tissue in cases 4 and 14. Histochemical examination for oxidative enzymes, ATPase, and phosphorylase in these six specimens revealed a normal checkerboard pattern and ratio of type I and type II fibres, in case 3 only. The muscles of case 4 showed a preponderance of type I fibres. One specimen from case 14, showed the same fibres reacting for both oxidative enzymes and phosphorylase, suggesting a lack of development of fibres. The intrafusal fibres were mainly of type I in all. Two possible pathogenetic mechanisms operating in early embryonic life, which may lead to the characteristic changes of AMC, are discussed: (1) a defect in the development of the muscle whereby the full recruitment of myoblasts from the mesenchyme of the limb-bud does not take place and muscles do not form adequately; (2) a lack of innervation of the muscles on account of arrested growth of anterior horn cells. The combined operation of both these mechanisms is also considered. Fibrous tissue replaces the muscle tissue that is lacking, and contractures and deformities ensue. The evidence gathered on our material, such as the very thin smooth muscle fibres, the large numbers of well-formed nerves and spindles especially in the repeat biopsies, and the above-mentioned histochemical feature, would appear to favour the hypothesis of ill-developed muscles in the production of AMC in the majority; in the rest denervation playing either a major or concurrent role. [ABSTRACT FROM PUBLISHER]

Sixteen cases with arthrogryposis multiplex congenita were examined clinically and electromyographically; three of them were re-examined later. Joint deformities were present in all extremities in 13 of the cases; in eight there was some degree of mental retardation. In two cases, there was clinical and electromyographic evidence of a myopathic disorder. In the majority, the appearances of the shoulder-neck region suggested a developmental defect. At the same time, selective weakness of muscles innervated by C5-C6 segments suggested a neuropathic disturbance. EMG revealed, in eight of 13 cases, clear evidence of denervation of muscles, but without any regenerative activity. The non-progressive nature of this disorder and capacity for improvement in muscle bulk and power suggest that denervation alone cannot explain the process. Re-examination of three patients after two to three years revealed persistence of the major deformities and muscle weakness noted earlier, with no appreciable deterioration. [ABSTRACT FROM PUBLISHER]

Sixteen cases with arthrogryposis multiplex congenita were examined clinically and electromyographically; three of them were re-examined later. Joint deformities were present in all extremities in 13 of the cases; in eight there was some degree of mental retardation. In two cases, there was clinical and electromyographic evidence of a myopathic disorder. In the majority, the appearances of the shoulder-neck region suggested a developmental defect. At the same time, selective weakness of muscles innervated by C5-C6 segments suggested a neuropathic disturbance. EMG revealed, in eight of 13 cases, clear evidence of denervation of muscles, but without any regenerative activity. The non-progressive nature of this disorder and capacity for improvement in muscle bulk and power suggest that denervation alone cannot explain the process. Re-examination of three patients after two to three years revealed persistence of the major deformities and muscle weakness noted earlier, with no appreciable deterioration. [ABSTRACT FROM AUTHOR]

Pathological findings are reported on 34 specimens from 16 cases of arthrogryposis multiplex congenita (AMC), including initial observations on paraffin sections from 28 muscles, and subsequent observations on six additional specimens from three of these cases studied both histologically and histochemically. Thirteen of the 34 specimens (from 11 cases) were histologically normal, probably on account of an unaffected muscle being sampled. The most constant pathological feature in the remaining specimens was a disorganization of the muscle fibres and fascicles by severe fibrosis; only three specimens (from two cases) did not show this. Very thin faintly striated muscle fibres embedded in this matrix were encountered in 10 specimens from nine cases. An attempt at grouping of these atrophic or ill-developed fibres was noticed in four specimens; but this may not be denervation atrophy. Two specimens (from two cases) showed `myopathic' features. Repeat biopsy after two to three years was carried out on two affected muscles each from three patients. Case 3 showed well preserved but uniformly small fibres. Case 4 showed extremely few and scattered small rounded fibres. Case 14 showed pronounced variation of fibre size in both, with both atrophic and hypertrophied fibres. Normal nerves and spindles were seen in all these six specimens irrespective of the state of the muscle, and excessive fibro-fatty tissue in cases 4 and 14. Histochemical examination for oxidative enzymes, ATPase, and phosphorylase in these six specimens revealed a normal checkerboard pattern and ratio of type I and type II fibres, in case 3 only. The muscles of case 4 showed a preponderance of type I fibres. One specimen from case 14, showed the same fibres reacting for both oxidative enzymes and phosphorylase, suggesting a lack of development of fibres. The intrafusal fibres were mainly of type I in all. Two possible pathogenetic mechanisms operating in early embryonic life, which may lead to the characteristic changes of AMC, are discussed: (1) a defect in the development of the muscle whereby the full recruitment of myoblasts from the mesenchyme of the limb-bud does not take place and muscles do not form adequately; (2) a lack of innervation of the muscles on account of arrested growth of anterior horn cells. The combined operation of both these mechanisms is also considered. Fibrous tissue replaces the muscle tissue that is lacking, and contractures and deformities ensue. The evidence gathered on our material, such as the very thin smooth muscle fibres, the large numbers of well-formed nerves and spindles especially in the repeat biopsies, and the above-mentioned histochemical feature, would appear to favour the hypothesis of ill-developed muscles in the production of AMC in the majority; in the rest denervation playing either a major or concurrent role. [ABSTRACT FROM AUTHOR]