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Biomedical subjects

R G Cooper

Publications and source records attributed to R G Cooper.

At least 73 records · Page 4Linked to original sources
PubMed1989

Myofibrillar activation failure in McArdle's disease.

Contractile properties of the adductor pollicis muscle were examined in 9 normal volunteers and 7 patients with histochemically proven myophosphorylase deficiency (McArdle's disease). Fatiguing contractions were produced by supramaximal stimulation of the ulnar nerve, delivered over a range of frequencies, to allow further examination of the mechanisms responsible for the premature fatigue in patients. The excessive reductions in force, demonstrated in patients at all frequencies, were not associated at high frequencies (50 and 100 Hz) with excessive declines in excitation (measured as compound muscle action potential). These results demonstrate that, in patients, myofibrillar activation failure occurs over and above that due to excitation failure. Abnormal slowing of relaxation mechanisms was also confirmed. These findings appear consistent with the hypothesis of inhibition of various ATPases by metabolic products. The observed, clear differences between normal subjects and myophosphorylase-deficient patients constitute the basis of an objective screening procedure for this and other glycolytic disorders.

Adolescent↗
PubMed1989

The development of structural complexity in the child's concept of family: the effect of cognitive stage, sex, and intactness of family.

Twenty-eight boys and 28 girls at each of the Piagetian preoperational, concrete operational, and formal operational cognitive stages were given an interview focusing on their concepts of family. Half of each group were from intact families, and half were from divorced families. Interviews were scored for two structural aspects of the concept of family: conceptual level, and use of dimensions that structure the concept. The complexity of children's concepts was strongly related to cognitive stage and, to a lesser degree, to sex. Frequency of use of concept dimensions was strongly affected by general developmental level, though not specifically cognitive stage, and by intactness of family, but to a lesser degree by sex. Specific information is provided on the effect of these factors on perceptions of family composition, parental roles, and breadth of family activities.

Adolescent↗
PubMed1988

Normal muscle strength and fatigability in patients with effort syndromes.

To examine fatigue mechanisms in an unselected series of patients with excess fatigue ("effort syndromes") their muscle function was compared with that of normal subjects. Voluntary performance was assessed with a cycle ergometer to exhaustion and by maximal isometric contractions of the quadriceps femoris. The mean maximal heart rate in patients during ergometry was 89% of the predicted rate, and quadriceps strength was either normal or was inappropriate for the available muscle, which suggested submaximal effort. Contractile performance was examined in the absence of volition with stimulated contractions of the adductor pollicis. During stimulated fatiguing activity patients were neither weaker nor more fatigable than controls; thus the excess fatigue experienced by the patients was not due to a defect of the contractile apparatus. The increased perception of effort must therefore be due to impairment of central rather than peripheral mechanisms. The optimal approach to treatment of effort syndromes combines physical and psychological techniques.

Adult↗
PubMed1988

Absence of excess peripheral muscle fatigue during beta-adrenoceptor blockade.

1. In eight normal volunteers, the adductor pollicis (AP) was fatigued using intermittent trains of programmed, supramaximal stimulation at 1, 10, 20, 50, 100 and 1 Hz. Activity protocols were performed both with and without circulatory occlusion, both without and during propranolol 80 mg thrice daily in order to investigate the effects of beta-adrenoceptor blockade on 'peripheral' fatigue mechanisms. 2. The degree of beta-adrenoceptor blockade was assessed by the reduction of exercise tachycardia during cycle ergometry, e.g. pulse rates at 210 watts were reduced from 190 +/- 15 to 127 +/- 5 beats min-1 (mean +/- 1 s.d.) indicating that beta-adrenoceptor blockade was substantial and highly significant (P less than 0.001). 3. Before, during and following fatiguing activity with circulatory occlusion force declines were identical during and without beta-adrenoceptor blockade. During and following activity without occlusion, there were slight declines in force which were questionably significantly different at 20 Hz (P less than 0.05). 4. The compound muscle action potential (CMAP) amplitude, measured from the skin surface over the muscle, was unaltered by beta-adrenoceptor blockade before, during or after activity whether with or without circulatory occlusion. 5. The maximal relaxation rate (MRR) was not significantly reduced in previously unfatigued muscle during beta-adrenoceptor blockade. During activity, both with and without circulatory occlusion, there was no evidence that MRR was reduced significantly more during beta-adrenoceptor blockade. 6. The absence of a convincing effect of beta-adrenoceptor blockade on peripheral fatigue mechanisms may indicate that central mechanisms are involved or that impairments of peripheral force production, of a specific nature or as a result of exacerbation of limitations of circulatory oxygen transport, though small are detected during voluntary exercise and give rise to increases in motor unit recruitment and/or firing rates, and hence increased perception of fatigue.

Adrenergic beta-Antagonists↗
PubMed1988

Mechanisms resisting fatigue in isometrically contracting human skeletal muscle.

Human adductor pollicis was fatigued during circulatory occlusion by supramaximal stimulation via the ulnar nerve using intermittent trains of stimuli in ascending (1, 10, 20, 50 and 100 Hz) and descending (100, 50, 20, 10 and 1 Hz) frequencies to investigate the contribution of relaxation rate slowing and post-tetanic potentiation (PTP) to fatigue resistance. At 50 and 100 Hz force was initially well maintained despite a marked loss of excitation as indicated by EMG, demonstrating the operation of a high-frequency 'safety factor' which appeared independent of the pattern of stimulation. At 10 Hz, force was initially potentiated before declining during both activity series. Potentiation was greater during the descending frequency series and the rate of decline of force, or fatigability, was reduced. The 'extra' low-frequency potentiation at 10 Hz was not simply the result of PTP of twitch force, since this declined more during the descending than during the ascending series, nor the result of maximal relaxation rate changes which were identical for both fatiguing series. It is hypothesized that the extra potentiation and reduced fatigability at low stimulation frequencies, when preceded by high frequency, is the result of increased myofibrillar Ca2+ availability and/or sensitivity. These findings may have important practical implications in relation to functional electrical stimulation techniques as used in paraplegia and in other areas of muscle research where fatigue is to be minimized.

Action Potentials↗
PubMed1988

Human muscle fatigue: frequency dependence of excitation and force generation.

1. Human adductor pollicis was fatigued using intermittent trains of programmed stimulation at 1, 10, 20, 50, 100 and 1 Hz, during activity with and without circulatory occlusion, to investigate the relationships between force generation, excitation and maximal relaxation rate (MRR). 2. The relationship between force generation and excitation was markedly dependent on stimulation frequency. Force loss was greatest at low frequencies, with little reduction in excitation, but as frequency increased force was well maintained despite marked loss of excitation. 3. Changes in MRR during activity and recovery were independent of stimulation frequency. 4. Marked increases of force at 1 Hz (pre-tetanic) and 10 Hz occurred, with little reduction in excitation, during activity with and without circulatory occlusion. This may be due to post-tetanic potentiation in addition to slowing of relaxation (MRR). 5. At high frequency a 'safety factor' may thus operate to maintain force, despite obvious loss of excitation, while at low frequencies there may be marked potentiation of force, despite unchanged excitation. These mechanisms could permit resistance to fatigue with muscle function remaining optimal over a range of conditions.

Action Potentials↗
PubMed1988

Physiological characterisation of the "warm up" effect of activity in patients with myotonic dystrophy.

Contractile properties of adductor pollicis muscle were examined over a range of stimulation frequencies in patients with myotonic dystrophy and normal subjects. In patients, fresh muscle demonstrated impaired relaxation, weakness at all frequencies and selective loss of force and excitation at high frequencies. During stimulated "fatiguing" activity, patients showed improvements in force and relaxation which appeared to result from normalisation of membrane excitation. Normal twitch potentiation also occurred during activity suggesting intact excitation-contraction coupling. These electrophysiological findings help to characterise and explain the "warm up" effect described by patients.

Adult↗
PubMed1988

The enterohepatic circulation of perhexiline metabolites in the male Wistar rat.

1. The biliary excretion of some perhexiline metabolites has been assessed in male Wistar rats with biliary cannulation. 2. After intragastric administration of perhexiline maleate (2 mg/kg body weight) multiple perhexiline metabolites were detected in bile. 3. When aliquots of this metabolite-laden bile were administered intraduoduodenally to further 'recipient' rats with biliary cannulation, similar metabolites were detected in the bile of these rats, but at reduced concentrations equivalent to 30-35% of those present in the bile of 'donor' rats. 4. These findings indicate that in the male Wistar rat, there may be substantial enterohepatic circulation of some perhexiline metabolites.

Animals↗
PubMed1988

Evaluating clinical competence with the new Fieldwork Evaluation.

The new Fieldwork Evaluation for the Occupational Therapist has been developed and tested through a series of field tests. With use, careful attention to issues arising from its application, and additional research, the Fieldwork Evaluation can be retained and updated to meet changes in clinical education and evaluation procedures.

Clinical Competence↗
PubMed1988

Technique for physiological examination of canine skeletal muscle in vivo.

A technique is described for studying the physiological function of canine skeletal muscle in vivo. The contractile properties of the tarsal flexor muscles were examined in three beagle dogs under general anaesthesia. The force responses to electrical stimulation of the common peroneal nerve were measured at various frequencies to determine the frequency:force relationship for this muscle group. Fatigue characteristics were also examined during intermittent stimulated activity delivered in a set pattern of frequencies. The results provide quantitative characterisation of muscle function which is repeatable. The technique described could be applied to other animals and is a potentially powerful tool for evaluating the effects of drugs on muscle performance.

Animals↗
PubMed1988

Adjuvant chemotherapy for breast cancer: 20 years experience using CVFMP chemotherapy.

In late 1963, we embarked on a program that combined oral prednisone and oral cyclophosphamide (Cytoxan) with intravenous (IV) vincristine, fluorouracil, and methotrexate (CVFMP). The initial 60 patients had an 80% response. Since then, a multitude of different combinations and variations in drug dosage and timing have been used. Basically, patient responses have improved from single-agent remissions of 15% to 30%, which lasted only 3 to 4 months to remissions now achieved in as many as 80% of patients which last for more than 1 year. We initiated a pilot study of adjuvant CVFMP therapy in 100 women who had four or more positive nodes at original mastectomy. Chemotherapy alone was used in 73 patients, while 27 received radiotherapy and then chemotherapy. Chemotherapy consisted of oral doses of prednisone, 0.75 mg/kg/d, in three divided doses. This was reduced weekly by 50% and discontinued in the majority of patients. Cyclophosphamide, 2 mg/kg/d, was administered orally in two or three divided doses. Both methotrexate, 0.6 to 0.7 mg/kg, and 5-fluorouracil, 12 mg/kg, were administered IV once a week. Vincristine, at a dose of 25 micrograms/kg was administered IV once a week for 5 weeks or until significant neurologic defect was noted. Of the 73 patients who received only chemotherapy, 19 relapsed; 80% of those 73 patients were disease free at 14 years. Of the 27 patients who received radiotherapy before CVFMP, 23 relapsed; less than 10% were disease free at 13 years.

Adult↗
PubMed1987

Studies on the metabolism of perhexiline in man.

We have studied the disposition of perhexiline and its two major metabolites, M1 and M3, in healthy volunteers and in patients with biliary T-tube drains after cholecystectomy. In healthy volunteers the genetic control for impaired hepatic oxidation is identical for debrisoquine, sparteine, and perhexiline. Poor metabolizers demonstrate markedly reduced production and excretion of the major metabolite, M1. Their production of M3 is also reduced, but to a lesser degree than for M1, confirming substrate stereoselectivity by hepatic oxidases. Biphasic urinary elimination of M1 and M3 is seen in intact extensive oxidizers, whereas only the first phase is apparent in patients with biliary T-tube drainage. This suggests the possibility of enterohepatic recycling of these compounds, which may account for their prolonged elimination. More than 90% of an ingested dose of perhexiline maleate remains unaccounted for at 24 h after ingestion, even in extensive metabolizers. A careful, radiolabelled tissue-distribution study is warranted to elucidate the complicated metabolic fate of perhexiline.

Adult↗
PubMed1986

Simultaneous determination of perhexiline and its monohydroxy metabolites in biological fluids by gas chromatography-electron-capture detection.

A rapid and sensitive method for the simultaneous determination of perhexiline and its cis-4-axial and trans-4-equatorial monohydroxy metabolites (M1 and M3, respectively) in human plasma, urine and bile is described. The assay utilises a single diethyl ether extraction, heptafluorobutyric acid anhydride derivatisation and separation and detection by gas chromatography-electron-capture detection. The limits of detection are 0.1 microgram/ml for perhexiline and 0.025 microgram/ml for the M1 and M3 metabolites. This method has been used in a five-day kinetic study of three healthy adult males who ingested a single 300-mg dose of perhexiline maleate. One of these volunteer subjects exhibited elevated plasma perhexiline and markedly reduced plasma and urinary M1 concentrations together with profoundly prolonged plasma and urinary M1 elimination times when compared with the other two subjects. These differences are thought to be of genetic origin. There were also obvious differences in urinary M3 concentrations which were discussed.

Adult↗
PubMed1985

Aspiration of oral contents in Parkinson's disease. A case report.

A patient with Parkinson's disease developed a non-ketotic hyperosmolar diabetic coma precipitated by chest infection. Initial improvement from treatment with intravenous insulin, ampicillin and fluid therapies was followed by severe deterioration and hypovolaemic shock. Further improvement occurred only when therapy directed against Gram-negative sepsis was added. A barium examination later demonstrated aspiration of oral contents with pulmonary soilage. The differences between the easily recognized early fulminating 'aspiration syndrome' caused by aspiration of gastric contents of low pH and the aspiration of oral contents, which may remain occult for many hours, is highlighted. Life-threatening Gram-negative or anaerobic infection may then occur but remain undiagnosed because the original aspiration of foreign material is unsuspected.

Diabetic Coma↗
PubMed1985

Acid and gastrin responses during intragastric titration in normal subjects and duodenal ulcer patients with G-cell hyperfunction.

Amino acid induced acid and gastrin responses during intragastric titration at pH 2.5 and 5.5 were compared in normal subjects and duodenal ulcer patients with G-cell hyperfunction. The latter were identified on the basis of raised basal or maximal acid outputs and increased gastrin responses to feeding. In normal subjects the mixed amino acid meal stimulated only modest increases in serum gastrin, and the highest observed increase was about 30% that after a standard meal. In contrast, in the G-cell hyperfunction group the highest gastrin concentrations were similar to those after a standard meal. In the G-cell hyperfunction group the increment in serum gastrin at pH 2.5 expressed as a proportion of that at pH 5.5 was 0.29 indicating that the capacity of acid to inhibit gastrin release was well established in these patients. Acid secretory rates were close to maximal at both pH 2.5 and 5.5 during intragastric titration in the ulcer patients, but in normal subjects acid output was about 50% maximal at 2.5 and close to maximal at 5.5. The results suggest that the enhanced gastrin response to feeding in G-cell hyperfunction patients is because of increased sensitivity to amino acid stimulation rather than to diminished acid-inhibitory mechanisms.

Adult↗