Biomedical subjects
N M Davidson
Publications and source records attributed to N M Davidson.
Training of doctors in developing countries.
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The etiology of peripartum cardiac failure.
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Peri-partum cardiac failure.
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Hazard of chemical sympathectomy.
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Bromocriptine suppression of the thyrotrophin response to thyrotrophin releasing hormone.
A single oral dose of 5 mg of bromocriptine significantly lowered the TSH response to 200 microgram TRH intravenously in eight healthy men compared with control experiments in the same subjects. This finding may be relevant in chronic bromocriptine therapy.
Hypothalmic-pituitary adrenal responsiveness to dexamethasone-insulin tolerance test in acromegalic patients before and during treatment with bromocriptine.
Insulin tolerance tests were carried out in 10 acromegalic patients after 1 mg dexamethasone had been given the previous evening (DEX-ITT). Nine patients showed a rise in plasma 11-OHCS and four patients showed a rise in plasma growth hormone (GH) levels. These responses were unaltered after treatment with bromocriptine 10 mg daily for two months. Basal plasma GH levels fell in 6 of the patients and the mean plasma GH levels of the 10 patients during an oral glucose tolerance test (OGTT) fell from 63.2 +/- 25.5 ng/ml before treatment to 53.0 +/- 27.1 ng/ml (mean +/- sem; p less than 0.05). These data fail to confirm a previous report of abnormal hypothalmic-pituitary-adrenal suppressibility during a DEX-ITT in acromegalic patients. They also indicate that bromcriptine does not alter the responses of plasma 11-OHCS and plasma GH to the DEX-ITT despite lowering plasma GH levels.
Peri-partum cardiac failure.
The syndrome of peri-partum cardiac failure (PPCF) has been studied in 224 women seen in three years in Zaria, in northern Nigeria. A very high proportion were rural Hausa patients. There was a seasonal peak in July, and the incidence was about one per cent of deliveries. The risk increased with both age and parity. Symptoms began most commonly in the second week after delivery, and admission was commonest in the fourth. Typical signs of cardiac failure were found, and pulsus alternans, atrio-ventricular valvular incompetence, transient systemic hypertension and splenomegaly were common. The chest radiograph showed marked cardiomegaly, and extrasystoles and inverted T waves were often present in the electrocardiogram (ECG). Hypoalbuminaemia was common. Digoxin and diuretics were rapidly effective, causing a mean weight loss of 29 per cent in 15 days, resolution of hypertension, and a fall in the cardio-thoracic ratio (CTR) from 61 to 53 per cent. During the first year after diagnosis, the CTR became normal in 82 per cent of patients, and the ECG in 60 per cent. PPCF recurred, again with the same seasonal variation, after 19 per cent of subsequent pregnancies. During follow up for two to five years, 22 per cent of the women became hypertensive, and 11 per cent died. The prognosis was worst in those with an arrhythmia, hypertension, sustained cardiomegaly or aged 30 or more. Asymtomatic post-partum hypertension (PPHT) was found in 61 per cent of normal Hausa women, with a seasonal peak in May, especially in those with hypertension during pregnancy or labour, and twin pregnancies. Peri-partum cardiac failure may be due to the combined pressure load of PPHT, the volume load from eating the customary sodium-rich kanwa, and the cardiovascular demands of heat, both climatic and traditionally self-imposed.
Seasonal variation of cardiac failure in northern Nigeria.
The number of patients with cardiac failure admitted to hospital in Zaria, Nigeria, month by month during 1972-75 differed highly significantly between the cooler dry months and the hot wet months. The reasons are uncertain, but seasonal changes in blood-pressure and the effects of heat on the circulation and of humidity on the efficiency of sweating may be responsible.
Glibenclamide and syndrome of inappropriate secretion of antidiuretic hormone.
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Observations in man of hypoglycaemia during selective and non-selective beta-blockade.
The acute hypoglycaemic reaction is accompanied by a rise in systolic and a slight fall in diastolic blood pressure and a tachycardia. In contrast, during beta-blockade with propranolol there is a rise of both systolic and diastolic blood pressures and bradycardia. Restoration of blood glucose to normal is delayed. With metoprolol there is a lesser increase in diastolic blood pressure and a slight tachycardia. Restoration of the blood glucose to normal is little delayed. When patients liable to hypoglycaemia require a beta-blocking agent, it is suggested that a selective blocker such as metoprolol should be used.
Pathophysiologic studies in human rabies.
Six patients with proved rabies were studied with a combination of clinical, physiologic and pathologic technics. Three were given a type of intensive care but died with evidence of respiratory failure. Although circulatory failure did not develop in any of the six patients, three had supraventricular arrhythmias: interstitial myocarditis was found in one of these and rabies virus was isolated from the myocardium of another. Inspiratory muscle spasm was the dominant clinical feature in all cases. This occurred as part of the hydrophobic response and followed stimulation of the upper respiratory tract and skin. Hydrophobia may represent an exaggerated respiratory tract irritant reflex with associated arousal. Later in the course of the disease, various patterns of periodic and ataxic breathing were observed. Widespread brain stem encephalitis was discovered at autopsy, with particular involvement of the neighborhood of the nucleus ambiguous in two of three patients examined. In one patient cerebral metabolism was grossly abnormal, with greatly reduced cerebral oxygen consumption suggesting irreversible brain damage. Respiratory and circulatory disturbances may well be immediate causes of death in patients with rabies, but the present studies reemphasize the severity of the encephalitis which remains the ultimate barrier to survival. In the developing countries in which rabies is still a major problem and in which the cost precludes intensive care, the clinical management of rabies can aim only to reduce suffering by heavy sedation.
Bites by the night adder (Causus maculatus) and burrowing vipers (genus Atractaspis) in Nigeria.
Nineteen patients proven to have been bitten by the small African adders Causus maculatus, Atractapis dahomeyensis and A. microlepidota were studied in the Nigerian savanna region. One of the patients bitten by C. maculatus was drowsy, hypotensive and flaccid on admission but recovered without treatment. Mild or moderate local swelling, local lymphadenitis and mild fever were the only other features in this group. None of the patients bitten by Atractaspis had signs of systemic envenoming apart from moderate fever. Local blistering appeared in two cases but did not progress to necrosis. No patient showed any disturbance of blood coagulation, or evidence of spontaneous hemorrhage or of cranial nerve lesions. The small literature on the effects of Causus and Atractaspis venoms in man and in laboratory animals is reviewed. It appears that bites by these species are very unlikely to cause serious ill effects. A few deaths from Atractaspis bites have been reported, but the danger from these species has been exaggerated.
T, B and K cells in autoimmune thyroid disease.
The K-cell cytotoxic activity of peripheral blood lymphoid cells from 104 patients with autoimmune thyroid disease and from age and sex matched control subjects was measured using chicken erythrocytes as target cells. Patients with Hashimoto thyroiditis,primary hypothyroidism and thyrotoxicosis who were either newly diagnosed and untreated or had received therapy for less than or equal to 1 year showed a significant increase in K-cell cytotoxic activity. Patients who had received treatment for greater than 1 year and less than or equal to 5 years showed no such comparable increase in cytotoxic activity. Within the group of patients with untreated thyrotoxicosis it was found that K-cell cytotoxic activity was related to both goitre size and serum antibody titre. Thus patients with little or no goitre showed a highly significant elevation of cytotoxic activity whereas patients with moderate to large goitres gave values within the normal range. Similarly patients with no detectable serum thyroid autoantibodies showed high K-cell activity while patients with positive antibody titres did not. It was also shown that neither the absolute number nor the proportion of circulating T and B lymphocytes in patients with autoimmune thyroid disease as assessed by the sheep red cell rosette method and by indirect immunofluorescence was significantly different from that observed in the normal control population. No correlation was found between peripheral blood K-cell cytotoxic activity and the percentage of circulating null cells, i.e. 100-(percentage T + percentage B) in either patients or control subjects.
Necrosis, haemorrhage and complement depletion following bites by the spitting cobra (Naja nigricollis).
The Spitting Cobra, Naja nigricollis, is widely and densely distributed in Africa. Fourteen patients with proven N. nigricollis bites, who were seen in the savanna region of Nigeria, did not exhibit the neurological signs, such as cranial nerve lesions and respiratory paralysis, expected following Elapid poisoning. All had local swelling, in eight cases involving the entire limb, and ten developed local tissue necrosis. Spontaneous haemorrhage was detected in three cases and was the probable cause of death in one of them; the other death in this series was unexplained. Haematological abnormalities included prolonged clot lysis anf failure of clot retraction due to a platelet defect. There was no specific deficit in clotting factors and a delayed rise in fibrin degradation products was attributed to extensive tissue damage at the site of the bit. Most patients showed depletion of complement component C3 and glycine-rich beta-glycoprotein (GBG), suggesting activation of the alternative pathway of complement fixation. There was evidence of hepatocellular damage in two out of six patients investigated. There was no evidence that specific polyvalent antivenoms, used in doses of up to 80 ml, prevented any of the effects of N. nigricollis venom. Clinical laboratory diagnosis is discussed. In the past many bites were wrongly classified as viper bites on the basis of clinical findings. Immunodiagnosis is a promising method for assessing the true importance of N. nigricollis bite in West Africa.
Inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC) as a means of detection of immune complexes in the sera of patients with thyroid disorders and bronchogenic carcinoma.
Circulating immune complexes in the sera of patients with thyroid disorders or bronchogenic carcinoma were investigated using an assay system based on the inhibition of the ADCC activity of rat spleen cells. Increased inhibition, as compared with that of the sera of age and sex matched controls, was found in patients with thashimoto thyroiditis, primary hypothyroidism and bronchogenic carcinoma. The degree of inhibition in the first two groups was markedly increased compared with control sera of the same IgG content. However, the results in the lung cancer group were slightly but not significantly greater than in controls with the same level of IgG. Increased IgG levels were found in patients with thashimoto thyroiditis and thyrotoxicosis, and also in patients with bronchogenic carcinoma who had mediastinal gland involvement. The lower level of sensitivity of the assay system was approximately 600 ng added aggregated IgG, corresponding to a concentration of 6mu g/ml in the sample assayed. It is possible that circulating immune complexes may exist in lung cancer, but at a level below that of the present assay system.
Bites by puff-adder (Bitis arietans) in Nigeria, and value of antivenom.
Ten patients bitten by the puff-adder (Bitis arietans) were studied in the North of Nigeria. Six showed severe local signs, and four also had evidence of systemic envenoming, including spontaneous bleeding with thrombocytopenia, hypotension, and bradycardia. Two patients died after developing circulatory collapse and renal failure. Antivenom and intravenous fluid restored blood pressure in two hypotensive patients, and antivenom probably prevented the development of local necrosis in four others with massive local swelling. Victims of B arietans who have swelling of more than half the bitten limb or show signs of systemic envenoming should be given at least 80 ml of specific polyvalent antivenom and watched carefully for signs of circulatory collapse. Debridement of necrotic tissue may be necessary.
Demonstration during life of rabies antigen in humans.
In three cases of human rabies, in which the diagnosis was proved postmortem, rabies antigen was detected by direct immunofluorescence of frozen sections of facial skin. The antigen was thought to be in nerve fibers in association with hair follicles. Development of this technique might enable the establishment of a method for the diagnosis of human rabies during life.