Biomedical subjects
Publications and source records attributed to D A Gibson.
The benefits and pitfalls of applying media and communications techniques to the education of health professionals are considered in the context of their use in the classroom, for independent study and for distance education. The difficulties are emphasized for managing learning materials of this kind, and for keeping them up-to-date.
In the foetal sheep, administration of morphine induces apnoea followed by hyperpnoea; during hyperpnoea the foetus arouses. We tested the hypothesis that naloxone, an opiate antagonist, would block these responses. In 14 foetal sheep between 123 and 140 days of gestation, we measured electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (EMGdi), blood pressure and amniotic pressure. Morphine (1 mg/kg) was injected in the foetal jugular vein during low-voltage ECoG. Saline or naloxone (0.1, 0.5 and 2.0 mg) were given, in randomized order, before the morphine injection, shortly after morphine injection during apnoea, and during maximum hyperpnoea. Saline alone had no effect on breathing or behaviour. When saline and naloxone preceded the morphine injection the length of apnoea was 26.6 +/- 7.7 and 19.5 +/- 7.0 min (SEM, P = 0.25) while the length of sustained hyperpnoea was 104.8 +/- 11.4 and 29.6 +/- 8.4 min respectively (P = 0.001). When administered during the maximum breathing response, naloxone decreased the length of breathing from 92.2 +/- 8.4 (saline) to 8.8 +/- 2.9 min (P = 0.001). Respiratory output (fEMGdi x f) also decreased from 6545 +/- 912 arbitrary units post saline to 3841 +/- 629 arbitrary units after naloxone (P = 0.05). Arousal disappeared with the decrease in breathing response. The negligible effect of naloxone on apnoea and its strong inhibition of hyperpnoea suggest that morphine may act on two distinct central regions or on two subtypes of opioid receptors to produce apnoea, hyperpnoea and arousal.
In the unanesthetized fetal sheep the administration of morphine causes initial apnoea followed by hyperpnoea. We thought that a section of the brain at midcollicular level might separate these two effects. Therefore we sectioned the brain stem of five fetuses at 132 +/- 1 (SEM) days of gestation and compared their responses to morphine (17 experiments) with that observed in seven intact fetuses at similar gestational ages (15 experiments). Brain stem sections were confirmed morphologically and histologically. Morphine, 1 mg/kg was injected in the fetal jugular vein during low-voltage electrocortical activity (ECoG). We measured ECoG, eye movements, diaphragmatic activity, blood pressure and amniotic pressure. Sectioned fetuses before the administration of morphine had a complete dissociation between ECoG and breathing activity. With the administration of morphine we found: (i) the length of the apnoea was 139.8 +/- 15.5 min in sectioned fetuses and 17.0 +/- 5.8 min in intact fetuses (P less than 0.01); and (ii) there was no hyperpneic response in the sectioned fetus whereas the length of hyperpnoea in the intact group was 99.1 +/- 11.8 min (P less than 0.001). The results support the idea of two central distinct areas of action of morphine in the fetal brain. The absence of hyperpnoea in the sectioned fetuses suggests that neurons inhibiting the 'respiratory neurons' are located rostrally to the mid-collicular line.
To define the dose response of apnea and breathing to morphine we studied 12 fetuses at 116-141 days of gestation using our window technique. We instrumented the fetus to record electrocortical activity (ECoG), eye movements (EOG), diaphragmatic activity (integral of EMGdi), heart rate, carotid blood pressure, and amniotic pressure. Saline and morphine in doses of 0.03, 0.1, 0.5, 1, and 3 mg/kg were injected in random order in the jugular vein of the fetus during low-voltage ECoG. Fetuses were videotaped for evaluation of fetal behavior. We found 1) that saline did not elicit a response; 2) apnea, associated with a change from low- to high-voltage ECoG, increased from 2.2 +/- 1.5 (SE) min in two fetuses at a dose of 0.03 mg to 20 +/- 6.3 min in seven fetuses at 3 mg/kg (P less than 0.005); 3) the length of the breathing responses, associated with a change from high- to low-voltage ECoG, were 15 +/- 1.8 and 135.9 +/- 18.1 min (P less than 0.0005); 4) integral of EMGdi X frequency, an index equivalent to minute ventilation, increased from 1,763 +/- 317 arbitrary units to 10,658 +/- 1,843 at 1.0 mg/kg and then decreased to 7,997 +/- 1,335 at 3.0 mg/kg. These changes were related to a steady increase in integral of EMGdi, whereas frequency decreased at 3 mg/kg. There was an increase in breathing response to morphine plasma concentrations or morphine doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Stereospecific [3H]etorphine binding sites are present in neuronal-enriched cell cultures dissociated from 7-day-old chick embryonic brain. Moreover, binding was regulated by both ions and GTP in a manner similar to that of in vivo brain tissue. When cultures were exposed to N-LAAM (10(-6) M) from day 6 to day 7 or 8 and assayed for binding at day 8, Bmax was decreased and KD was increased. These findings support our view that primary neuronal cultures are a suitable model with which to study interactions of drugs with opiate receptors.
The problem of real distress from the discomfort of collapsing scoliosis is predictable in Duchenne muscular dystrophy (DMD). Once the lumbar curve has exceeded 35 degrees, further progression is inevitable. A vital capacity, then, of 35% or more permits consideration of spinal surgery. Using these indications, 24 patients with DMD had long Harrington instrumentations and spinal fusions from S1 up to the upper thoracic spine (T4, 5, or 6). After two weeks recumbent, they were mobilized wearing a light spinal support in their wheelchairs. The complications encountered are described in detail. One patient died two years after his operation from dystrophic cardiomyopathy. With a follow-up period of four months to 42 months, the rest of these patients are well and sitting with comfort. The authors think that this experience indicates that prophylactic spinal fusion deserves consideration in the care planned for these patients.
Mixed neuronal and nonneuronal cell cultures were obtained from 8-day-old chick embryos cerebral hemispheres and glial-enriched cultures were obtained from fifteen-day-old chick embryo cerebral hemispheres. Cultures were exposed to methadone, a narcotic drug, from days four to six. The activity of ornithine decarboxylase (ODC) was determined at day eight and the activity of cyclic nucleotide phosphohydrolase (CNP) was determined at day fifteen. Both ODC and CNP activity were higher in mixed neuronal-nonneuronal cell cultures treated with methadone as compared to control. No effect was observed in the neuronal-enriched or glial-enriched cultures. These findings are interpreted to reflect that neuronal-glial interaction is important in the response of primary neural cells to methadone.
Stereospecific [3H]etorphine binding has been detected in chick embryos as early as day 4 of incubation in both brain and body tissue. By day 10 of incubation [3H]etorphine stereospecific binding activity is not detectable in nonneuronal tissue. The ubiquitous opiate binding sites early in embryogenesis are high affinity and respond to ion and GTP regulation in a manner similar to adult brain tissue. We interpret our observations to indicate all embryonic cells prior to cell differentiation contain opiate receptors. Therefore, we propose that opiate receptors play a dual role; one function early in embryogenesis not associated with neurotransmitter regulation, and another function later in embryonic development and in the adult: the classical neurotransmitter regulatory function.
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This report describes an attempt to conduct (in 1978 during a period of one week) an intensive, thorough, and objective evaluation of a prosthetic control system in such a manner that the evaluation avoids what are seen as shortcomings common among evaluation procedures described in the literature. The evaluation, in terms of benefits to patients, involved consideration on an interdisciplinary basis among an engineering team, prosthetics team, and therapy team. Nine below-elbow and two forequarter amputees participated. The device evaluated was the University of New Brunswick 3-state myoelectric control system, in the 12-volt version designed in 1975. This system is intended for use where there are not enough control sites to permit use of an Otto Bock or similar control system, and permits on/off control of a powered hand or other device in two directions from a single muscle. Observations on each patient by the 14-person evaluation team are summarized, and an Appendix presents questionnaires with summarized responses of the subjects and their families.
Upper limb prostheses are often rejected because they do not provide the sensory feedback available from a normal hand. A system for providing sensory feedback has been developed at the University of New Brunswick for use with the three-state myoelectric controls prepared in the Bioengineering Institute there. Strain gauges mounted on the forefinger of an electric hand provide information which is processed electronically to cause a tingling sensation in the patient's stump, proportional in its intensity to the pinch force in the finger. This system has been used by a patient at the Ontario Crippled Children's Centre in Toronto, since June 1976. She uses it consistently with great satisfaction and enthusiasm. It gives her a sense of competence and confidence she does not have without it.
We assayed activities of monoamine oxidase (MAO) type B in blood platelets and type A (and B) in fibroblasts cultured from punch biopsy specimens of skin, as well as of catechol-O-methyltransferase (COMT) in erythrocytes and fibroblasts. Fibroblasts contained moderate amounts of both forms of MAO (types A and B) found in human brain and large amounts of COMT activity. Activities of both enzymes correlated poorly between fibroblasts and blood cells. Comparing carefully diagnosed chronic schizophrenics with age-matched normal young men, we found no difference in these biochemical variables, nor could we distinguish patients with paranoid symptoms. In contrast, we confirmed markedly lower MAO activities in platelet samples from chronic patients provided by colleagues at the National Institute of Mental Health. Results concerning MAO and COMT activities are now sufficiently inconsistently characteristic of schizophrenics as to question their clinical applicability and to indicate a need for further critical evaluation, with special attention to diagnosis, matching of subjects, and effects of possible spurious environmental variables.
Thirty-seven children in whom 46 triple arthrodeses had been performed were followed up for 19 to 33 years (average, 24 years). Better results were evident in patients who had been operated on because of poliomyelitis, pes cavus or pes planus than in patients operated on for club foot, cerebral palsy or spina bifida. The use of staples appeared to improve the result. A neutral position of the heel is desirable. Varus positions required revision in three patients. A heel-toe gait was noticeable in 74% of patients. Osteoarthritis occurred 24% and pseudarthrosis in 4% of our patients. In 91% of patients the functional result could be described as good or excellent.
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Skin fibroblast cultures were prepared from 21 men, and found to contain types A and B activity of monoamine oxidase, with a possible slight predominance of type A, as evaluated by substrate preferences and differential inhibition by clorgyline and deprenyl. Three women had similar activities. There was a close correlation of activities with different substrates, but there was no quantitative correlation between fibroblast and blood platelet enzyme (type B) activities. The fibroblasts also contained catechol-O-methyltransferase activity exceeding, but poorly correlated with, that in erythrocytes. Fibroblasts may be advantageous in studies of monoamine oxidase in man by providing both types of enzyme as found, for example, in the central nervous system, and by providing a means of removing many in vivo chemical influences from the cells in culture. Nevertheless, great caution must be exercised in generalizing results of this "model" to other tissues, since activities of both enzymes correlated poorly with those in blood cells of the same individuals.
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