School of Laboratory Medicine & Medical Sciences

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The pathological aspects of heart failure in the Natal African.
(1967) Kallichurum, Soromini.; Wainwright, J.
The aims and objects of this work, as outlined in the introduction, were to a s s e s s the necropsy incidence of deaths due to heart failure in the African in Durban, to a s s e s s the necropsy incidence of the various aetiological types of heart failure with particular reference to right ventricular hypertrophy and failure, and to compare and contrast the incidence, complications, morbidity and mortality of heart disease in the Natal African with the same in other African and racial groups, both in South African and elsewhere. Many of the points emerging from this work merely confirm what has long been known, but others refute previous concepts. The all-age average necropsy incidence of deaths from heart failure in the African in Durban is of the order of 8%. This percentage does not, unfortunately, lend itself to straight comparison with most other series because of the high infant mortality shown in the present study. However, in considering deaths due to heart failure in the 10-plus age groups, the African still shows a lower mortality from heart disease in comparison with figures obtained for Indians or those reported for the Coloured and White races in South Africa. There are six major causes of heart disease in the African, which in order of frequency are, rheumatic heart disease, hypertensive heart disease, cardiomyopathy, cor pulmonale, pericarditis, and syphilitic heart disease. While little difference is apparent in the incidence of rheumatic and hypertensive heart disease, and possibly cor pulmonale, among the various races, cardiomyopathy, pericarditis and syphilitic heart disease are far more important causes of heart failure in the African by contrast with the other racial groups in South Africa. Although coronary a r t e r y disease is by comparison very uncommon in the African, cardiomyopathy, pericarditis, and syphilitic heart disease together claim as many deaths from heart failure in these people as does coronary heart disease among the Indian and White races in the Republic. Except for minor variations in the incidence of certain aetiological types, and the geographical distribution of endomyocardial fibrosis and cardiomyopathy/. . cardiomyopathy, the g e n e r a l p a t t e r n of h e a r t d i s e a s e among the Africans in Natal a p p e a r s to be s i m i l a r to that r e p o r t e d from other P r o v i n c e s in South Africa and most other c o u n t r i e s on the continent. Rheumatic h e a r t d i s e a s e is r e s p o n s i b l e for 21. 5% of all deaths from congestive h e a r t failure in the African in Durban. The immediate and the l a t e c a r d i a c complications of r h e u m a t i c fever in the Durban African a r e , on the whole, found to be no different from those r e p o r t e d in W e s t e r n communities. The findings in t h i s study t h e r e f o r e refute the view that r h e u m a t i c h e a r t d i s e a se i s infrequent in the African after the age of 40 y e a r s , and failed to support the suggestion that the d i s e a s e affects them m o r e s e v e r e l y or that death from r h e u m a t i c heart d i s e a s e o c c u r s at an e a r l i e r age in t h i s r a c e . While it is a g r e e d that s e v e r e valvular deformity in young African subjects (under 15 y e a rs of age) o c c u r s c o m p a r a t i v e l y m o r e frequently, it must be stated that this is in no way p e c u l i a r to the African, similar lesions being o b s e r v e d in Indian s u b j e c t s of c o r r e s p o n d i n g age. Hypertensive h e a r t d i s e a s e is common among the African in Durban, accounting among t h em for 18. 9% of all deaths from congestive h e a r t f a i l u r e. While both e s s e n t i a l and secondary forms of h y p e r t e n s i o n occur in the local indigenous population, the former appears to be m o r e common, with a peak incidence in the seventh decade of life. Secondary hypertension, mostly r e n a l in origin, is an i m p o r t a n t cause of h y p e r t e n s i v e congestive c a r d i ac f a i l u r e in the fourth decade. The wide v a r i a t i o n s in the type of h y p e r t e n s i on r e p o r t e d from the different regions in Africa, and the doubt e x i s t i n g as r e g a r ds the significance of focal lesions in the kidneys, point towards the need for g e n e r a l l y accepted c r i t e r i a in the diagnosis of r e n a l hypertension, p a r t i c u l a r ly with r e g a r d to chronic phylonephritis. Cardiomyopathy c l a i m s 15. 8% of all deaths from congestive heart f a i l u r e in the local African population. While many of the pathological changes o c c u r r i n g in the h e a r t in t h i s d i s e a s e were found to be s i m i l a r to those of other i n v e s t i g a t o r s , c e r t a i n f e a t u r e s , relating to c a r d i a c hypertrophy and s t r u c t u r a l a l t e r a t i o n s in the pulmonary v e s s e l s , have been e s p e c i a l ly i n v e s t i g a t e d / . . . investigated and results obtained in this series of cases show that whereas pure right ventricular hypertrophy is uncommon in cardiomyopathy biventricular hypertrophy with predominance of the right ventricle is the most frequent form of cardiac enlargement in such cases. Equal hypertrophy of the ventricles is the next common form of enlargement; left ventricular predominance is by far the least frequent, and no case of exclusive left ventricular hypertrophy was encountered. Although structural alterations in the pulmonary a r t e r i e s , indicating pulmonary a r t e r i a l hypertension, were observed in a large number of cases investigated, such changes were in no way specific to cardiomyopathy, since similar changes were observed in cor pulmonale due to emphysema and also in some cases of hypertensive congestive heart failure. Structural alterations in the small muscular pulmonary a r t e r i e s and arterioles were also identical with those found in emphysema. Whereas fresh pulmonary emboli and infarcts were frequently encountered and were often of such degree as to be the immediate cause of death, chronic pulmonary thrombo-embolism of an extent sufficient to have been the cause of right ventricular predominance was seldom found. It is suggested that the cause of the pulmonary hypertension and certain pathological changes in the heart in cardiomyopathy may lie in some form of exogenous toxin, possibly related to the practice of herbal medication among the African people, which acts as an a r t e r i a l vasoconstrictor in both the pulmonary and systemic circulations. This would suggest that the a r t e r i a l changes observed in the lungs are probably the result and not the cause of pulmonary hypertension. The incidence of cor pulmonale as a cause of congestive heart failure among the African in Durban is of the order of 12%. It has been shown that almost one quarter of all cases of right ventricular failure remains undiagnosed, as regards aetiology, at routine necropsy. The latter finding pointed towards the need for an investigation of the causes of right ventricular failure in the African. Such a study was undertaken and special methods of investigation w e r e / . . . were used as aids towards a more conclusive diagnosis. This study showed fibrosing lung disease, due particularly to the late complications of pulmonary tuberculosis, to be the most important cause in the production of chronic cor pulmonale in the African in Durban. The development of cor pulmonale in such cases depends not only on the presence of pulmonary parenchymal damage by fibrosis, but also on the associated pleural thickening, adhesions between chest cage and diaphragm, emphysema, and the curtailment of the pulmonary a r t e r i a l bed. In this series, all cases of fibrosing lung disease with cor pulmonale investigated for cardiac hypertrophy by means of separate weighing of the ventricles, showed evidence of pure right ventricular enlargement, indicating no significant chronic burden on the left ventricle of a diastolic overload through bronchial shunting. Thrombo-embolic cor pulmonale, hitherto believed to be r a r e in the African, emerges as the most important cause of acute cor pulmonale and the second most common cause of the more chronic varieties of the disease. The usual pathological type of pulmonary thrombo-embolic disease observed in this study is one in which fairly large pulmonary a r t e r i e s , as opposed to those of microscopic size, were involved and in consequence infarction was frequent. The lack of completely organised lesions, and the relatively small increase in total heart weights (majority below 400 Gms) suggest a rapid course in these cases, measured in months rather than in years. The usual source for pulmonary emboli was found to be the veins draining the lower limbs, particularly the deep calf veins. Whereas a predisposing factor for the development of venous thrombosis was found in just over half the number of cases investigated, in 44% of all cases of thrombo-embolic cor pulmonale in this study no cause was found at necropsy for the peripheral venous thrombosis. Of the predisposing causes encountered a posteriorly placed amoebic liver abscess emerges as an interesting aetiologic factor in the development of thrombo-embolic cor pulmonale because of its ability to produce hepatic vein and inferior vena caval thrombosis. Emphysema, usually in association with chronic bronchitis, was found to be the third most common cause of chronic cor pulmonale among Africans/ . . . Africans in Durban, and was encountered mainly in its mixed form (centrilobular and panlobular). Although structural alterations in the pulmonary a r t e r i es were noted in a significant number these were sometimes of insufficient degree to be the cause of pulmonary hypertension, thereby suggesting some other factor in the production of a raised pulmonary a r t e r i a l p r e s s u r e . Results of separate ventricular weighing in these cases show exclusive right ventricular hypertrophy, again indicating strain solely on the right ventricle. Bilharzial cor pulmonale, although one of the r a r e r causes of cor pulmonale in the African in this series, is suspected to be probably more frequent than hitherto believed. The lack of obvious macroscopic changes in the lungs of such cases is stressed, and while this may account for omissions in diagnosis, a sudden recent increase in the incidence of bilharzial cor pulmonale might also suggest that the disease is becoming more severe. Primary pulmonary hypertension as a cause of cor pulmonale in the African is r a r e , being suspected in only one case in this series. In keeping with the generally high incidence of infective diseases in the African, pericarditis as a complication of tuberculosis and hepatic amoebiasis, and the cardiac complications of syphilitic aortitis still occupy major positions among the causes of congestive heart failure in this population; together accounting for 12.4% of all deaths from congestive heart failure. Tuberculosis and amoebiasis are important not only in the production of p e r i c a r d i t i s , but, as mentioned, also play an important part in the development of cor pulmonale. Syphilitic heart disease, besides being a significant factor in the production of congestive heart failure, is the most important cause of a sudden cardiac death in the African. In conclusion it may be said that while little can be achieved with regard to the control of diseases for which no cause has as yet been found, the elimination of infective conditions such as tuberculosis, amoebiasis and syphilis will result in a significant drop in the incidence of death and disability from heart failure in the African in Natal.
A study of some aspects of senescence in embryos of zea mays L.
(1968) Berjak, Patricia.; Villiers, T. A.
Abstract available in PDF file.
The effects of nerve stimulation on pacemaking activities of biological tissues.
(1973) Bhagat, Chotoo Ichharam.; Reid, John Victor Oswald.
The effects on the cardiac cycle length of stimulating the vagus nerves with single supramaximal electrical shocks depended upon when they were stimulated during the cycle. A maximum prolongation of the cardiac cycle was obtained when the vagi were stimulated 167 msec (SD±64) after the peak of an electrocardiogram P wave. The interval between a P wave and the subsequent vagal stimulation was called Pl-St interval. Pl-St(max) was the Pl-St interval at which maximum prolongation of the cardiac cycle occurred. Pl-St(max) increased significantly (p (0.001) with longer cardiac cycles. When the Pl-St intervals were shorter or longer than 167 msec (SD±64) the effects of vagal stimulation were less. The latent period for the effects of vagal stimulation was 195 msec (SD±32) The latent period also increased significantly (p(O.Ol) with longer cardiac cycles. The rise time of the vagal effect, obtained by subtracting (Pl-St(max)+ latent period) from the control cardiac cycle length, was 124 msec (SD+31) and occurred between Pl-St intervals of 167 msec (SD±64) and 291 msec (SD±70). The rise time did not vary with cardiac cycle length (p) 0.1), but the magnitude of the maximum response to vagal stimulation was inversely proportional to rise time (p <. 0.02). The peak response to vagal stimulation must have occurred when the vagal effects pegan somewhere in the middle of diastolic depolarization of the pacemaker cells in the S-A node. The reasons for this were discussed. The half-decay time for the effects of vagal stimulation was 210 msec (SD±102). The slope of the curve relating the prolongation of the cardiac cycle length to Pl-St is positive at Pl-St intervals less than 167 msec (SD±64) and negative at Pl-St intervals between 167 msec (SD±64) and 291 msec (SD±90). The positive slope ranged from 0.13 to 0.48 with a mean of 0.23. The paradoxical responses of the S-A node to vagal inhibitory input obtained by Reid (1969), Levy et al (1969)and Dong and Reitz (1970) would be explained by the dependence of the cardiac cycle length upon the time of arrival of vagal stimulus in relation to the previous P wave and upon the slope of the curve relating the prolongation of the cardiac cycle length to Pl-St interval being positive and between zero and two at Pl-St intervals less than 167 msec (SD±64. The effects of single shock stimulation of the vagus nerves persisted for 3.890 sec (SD+l.255)7 the number of cardiac cycles involved varied between 5 and 11. The duration of the effects of vagal stimulation did not depend upon when during the cardiac cycle the vagi were stimulated. A "dip" in the response to vagal stimulation was present in all the experiments. The possibility of the "dip" phenomenon being due to simultaneous stimulation of the sympathetic fibres in the vago-sympathetic trunk was ruled out. It is suggested that the "dip" phenomenon may be due to transient accumulation of K+ in the interstitial fluid surrounding the pacemaker cells in the S-A node.There was no paradoxical response of the smooth muscle in the distal colon of the adult rabbit when the frequency of sympathetic inhibitory input was continuously increased. A paradoxical response in the frequency but not in the size of the contraction of the smooth muscle was obtained when the sympathetic nerves were stimulated with bursts of stimuli, each burst consisting of 5-40 impulses, 10 msec apart. One may conclude from this that the delay of the next spontaneous contraction but not the inhibition of the size of smooth muscle contraction is dependent upon the arrival time of a burst of stimuli during a contraction cycle. This was confirmed in an experiment when the sympathetic nerves were stimulated with single bursts of stimuli applied at different times during the contraction cycle. It is unlikely that such a paradoxical response would occur under physiological conditions as this would require the natural sympathetic efferent discharges to the smooth muscle to occur in regular bursts, each burst consisting of impulses at a high frequency. Stimulation of the sympathetic nerves at 3, 5, 10 and 25 PPS caused an inhibition of the size and frequency of smooth muscle contraction in the distal colon of the newborn rabbit. Assuming that the cholinergic fibres are excitatory there is therefore no evidence for the sympathetic fibres to the distal colon being cholinergic in the newborn rabbit. This is contrary to Burn's (1968) report of the sympathetic fibres being motor and cholinergic to the small intestinal smooth muscle in the newborn rabbit.The heart rate increased rapidly at the onset of exercise and then more gradually over the rest of the exercise period. The initial increase in the heart rate during exercise was not affected by adrenergic blockade but the subsequent increase in heart rate was significantly reduced by adrenergic blockade. Hence the increase in heart rate at the onset of exercise is due primarily to a decrease in the cardiac vagal efferent discharge, whereas the subsequent increase in heart rate is due to both a further decrease ln vagal discharge and an increase in sympathetic discharge to the S-A node. In almost all the sub jects there was initially a rapid decline in the heart rate in the post-exercise period, but subsequently the heart rate returned to resting levels in a variety of ways. These were classified into 5 types. Of particular interest to the present study was the Type V pattern of heart rate change. This was characterised by an increase in heart rate of 6 beats or more per minute during the post-exercise period, with or without superimposed arrhythmia. The Type V pattern may be the equivalent of the paradoxical responses to inhibitory input demonstrated in animal experiments i.e. an increase in the heart rate with increasing vagal stimulation frequency. Type V pattern occurred more frequently at mild exercise levels (4 out of 14) than at moderate exercise level (lout of 14) and also more frequently in adrenergic blocked individuals (11 out of 28) than in control subjects (5 out of 28) It is suggested that the sympathetic effects on the P-R interval and arterial baroreceptor modulation of vagal efferent discharge protect again st the occurrence of paradoxical responses to vagal inhibitory input. They may do so by confining the vagal discharge to the rise time of vagal effect during the cardiac cycle. On the other hand the Type V pattern in p-adrenergic blocked individuals may be due to a decrease in the vagal discharge, in which case Type V pattern would not be a paradoxical response. The changes in minute ventilation in the post-exercise period were also variable. Besides a gradual decline in minute ventilation there were also gradual increases and sudden increases and decreases in minute ventilation. These may represent a form of paradoxical response to increasing inhibitory input and decreasing excitatory input to the respiratory neurones in man. However, all the changes in minute ventilation could also be explained by fluctuating excitatory and inhibitory neural input to the respiratory neurones.
The RH Factor : a clinical and fundamental study of its significance in ISO- and Auto-Haemolytic anaemias.
(1973) Vos, Gerhardus Hubertus.; Villiers, T. A.; Bain, Peter G.
No abstract available.
Experimental diabetes in the baboon.
(1979) Naidoo, Dayananthan.; Asmal, A. C.
The object of the present study was to determine simultaneously aspects of hepatic and peripheral glucose metabolism in the intact baboon. Isotopic techniques were used to study glucose turnover rates, glucose recycling, glucose pool and space, and the forearm technique to study peripheral exchange of glucose. The results obtained in the normal animals acted as reference values for each animal. Thereafter diabetes mellitus was produced with streptozotocin, a drug causing destruction of the beta cells of the pancreatic islets. Experiments were then repeated in the acutely diabetic baboon and the nature and extent of the abnormalities in glucose metabolism documented. Lactate metabolism and peripheral lipid metabolism were included in the study in order to establish any interrelationships with glucose metabolism and to determine the abnormalities resulting from the production of diabetes. In the normal animal the turnover rate of lactate was greater than glucose although the lactate pool was much smaller than the glucose pool. After producing diabetes glucose turnover rates increased threefold and correlated with the severity of hyperglycaemia. A significant increase in lactate turnover rates was noted but the increase was less than in the case of glucose turnover rates. The formation of glucose from lactate increased significantly but the fraction of the lactate turnover rate converted to glucose was unchanged. The glucose pool increased nearly threefold and correlated with the increase in glucose turnover rate. There was a significant but smaller increase in lactate pool which correlated with the increase in lactate turnover rate. Both glucose and lactate space decreased after diabetes but the decrease did not correlate with the severity of hyperglycaemia. In the majority of diabetic animals there was no glucose utilization in the forearm, and in fact glucose release was observed. Increased production of lactate occurred in the forearm of the diabetic baboon, despite decreased glucose utilization.Arterial levels of triglyceride and free fatty acid increased threefold after diabetes while the free glycerol level doubled. In the normal animal the general pattern of exchange in the forearm consisted of triglyceride and free fatty acid uptake and free glycerol release. In the diabetic animal triglyceride and free fatty acid release was observed, while the release of free glycerol was decreased. The pattern of forearm metabolism in the diabetic animals was variable and not as consistent as before the production of diabetes. Several interrelationships between glucose, lactate and lipid metabolism were noted. The baboons used in this study showed extreme sensitivity to the metabolic effects of Streptozotocin Diabetes. Hyperglycaemia increased in severity and ketoacidosis invariably developed in the second week. The animals were not treated with insulin and death from severe uncontrolled diabetes occurred in nearly all animals within two weeks. This study has demonstrated the severe abnormalities in hepatic and peripheral glucose metabolism in diabetes. The simultaneous pathogenesis of these abnormalities and their importance in the development of the acute diabetic syndrome have been defined. Associated abnormalities in lactate metabolism and lipid metabolism have also been documented.
Non-insulin-dependent diabetes in young Indians : a clinical and biochemical study.
(1982) Jialal, Ishwarlal.
One of the earliest recorded references to polyuria is found in the Papyrus Ebers (1500 BC) and much later the occurrence of "honey urine" was noted by an ancient Hindu physician, Sushrutha, in old Indian Sanskrit (400 BC). However, the first good clinical description of the disease is ascribed to Celsus, although the name "diabetes" was introduced by Aretaeus of Cappadocia. The body of knowledge which has accumulated since these early recordings to the present state of the art reflects a most impressive sojourn, punctuated by many milestones, each adding impetus to future attempts in a relentless endeavour to unravel the aetiopathogenesis of this common malady. However, this "sweet evil" (diabetes) remains an enigma in many ways. There is little doubt today that there are 2 major types of diabetes: juvenile onset diabetes, presently known as insulin-dependent diabetes mellitus (IDDM) and maturity onset diabetes, referred to as non-insulin dependent diabetes mellitus (NIDDM). In NIDDM aggregation of HLA types, evidence of cell mediated immunity and the presence of circulating islet cell antibodies, which are characteristically associated with IDDM, are not found. There is also a vast difference in concordance of diabetes in the co-twins between the two types of diabetes suggesting that a different mixture of genetic and environmental factors is operative in the pathogenesis of these two types of diabetes. In I960, Fajans and Conn drew attention to the existence of a form of diabetes with an onset before the age of 35 years. Their patients showed a substantial improvement in glucose tolerance when treated with an oral hypoglycaemic agent, tolbutamide. Subsequent to this report numerous studies from various parts of the world confirmed this entity of non-insulin dependent diabetes in the young (NIDDY) in White Caucasians. There are, however, several different syndromes presenting as mild carbohydrate intolerance in the first two to three decades of life. The classical form of NIDDY is a mild non-insulin requiring form of diabetes in which the disorder is inherited as a dominant trait; there is little progression of glucose intolerance, if any, with time, and the diabetes is rarely accompanied by vascular complications. This subtype of diabetes is referred to as MODY (maturity onset diabetes in the young) and thus constitutes a subset under the broad umbrella of NIDDY. However, recently compelling evidence for heterogeneity within MODY has been presented. This evidence is based on the prevalence of certain HLA antigens, insulin responses to oral glucose, occurrence of vascular complications, progression of hyperglycaemia to the stage of insulin requirement and failure to demonstrate autosomal dominant inheritance in some families studied. In the South African Indian population which has a high prevalence of diabetes, Campbell was the first to draw attention to NIDDY in Indians more than two decades ago. Since this initial report, nobody has really studied NIDDY in any depth in South Africa and certainly not in the Indian population. NIDDY in the local Indian population is of particular interest for the obvious reason that diagnostic and management problems arise daily in a population with a high prevalence of non-insulin dependent diabetes. It is vital that the clinical features, endocrine and associated biochemical aberrations be known in detail if this condition is to be managed appropriately and adequately. A study of these aspects therefore became the primary task of this thesis. To pre-empt any challenge that patients were not really diabetic, the strict criteria of the W.H.O. for the diagnosis of diabetes were chosen. It should therefore be borne in mind throughout this study that a group of rather severe diabetics were selected by design. The patients studied represent the rather extreme end of the spectrum. But, in the event, this selection proved advantageous in that it covered an unstudied part of the spectrum and some light could be shed on the natural history of the disorder. In the long term the purpose was to prepare the ground for what must become the thrust of future studies, namely the biochemical pathogenesis of NIDDM. If it is true that some forms of NIDDY are inherited dominantly, existing techniques should make it possible to identify a gene(s) locus and if this is done the biochemical basis of this disorder must be identifiable. In the present study direct examination of these aspects were not undertaken, but an attempt was certainly made to pinpoint those biochemical abnormalities which are perhaps primary or central to the whole disorder.
A study of diabetes mellitus in young Africans and Indians (age of onset under 35) in Natal.
(1982) Mahomed, Abdool Khalek Omar.
No abstract available.
A clinico-pathological and biochemical study of the toxicity of callilepis laureola (impila)
(1983) Bhoola, Keshavlal Daya Narotam.; Leary, W. P. P.
This study was undertaken as a result of the occurrence of a large number of deaths among the local Black population from the use of herbal medicines prepared from the rootstock of Callilepis laureola known to the Zulus as impila. The salient clinico-pathological features in these cases were hypoglycaemia, centrilobular zonal liver necrosis and acute renal tubular necrosis. The purpose of this study was to investigate fully the clinical, biochemical and pathological aspects of the toxicity produced by Callilepis laureola (impila). The first part of the investigation consisted of an assessment of all cases of death due to acute liver necrosis diagnosed by necropsy at King Edward VIII Hospital, Durban. A review of clinical and necropsy records of 21687 consecutive post-mortems performed on Black patients during a 20 year period showed that acute liver necrosis was the major contributing cause of death in 447 patients. In 263 cases the hepatic lesion was centri lobular zonal necrosis with associated acute tubular necrosis (Group A); while in 184 cases the I iver necrosis was of the massive or submassive type (Group B). A comparative assessment of these two groups as regards necropsy prevalence, age and sex distribution and the clinical, biochemical and pathological findings was undertaken. This study shows that the combination of hypoglycaemia, centri lobular zonal liver necrosis and acute renal tubular necrosis due to Callilepis laureola (impila) poisoning is a distinct clinico-pathological entity and differentiates this group from cases of acute massive and submassive liver necrosis resulting in most cases from fulminant viral hepatitis. In the search for the toxic components of the root of Callilepsis laureola several compounds were isolated. These were atractyloside, carboxyatractyloside, two thymol related oils and a carbohydrate. The thymol related oils as well as the carbohydrate were found to be non-toxic in laboratory rats. The crude methanol extract of the root of Callilepsis laureola, when injected intraperitoneally into laboratory rats, produced centrilobular zonal liver necrosis and acute renal tubular necrosis, the lesions identical to those seen in patients who had died after intake of impila prescribed by witchdoctors and other dispensers of herbal medicines. On the other hand intraperitoneal injections of the purified compound atractyloside caused acute renal tubular necrosis and hypoglycaemia in laboratory rats but failed to produce liver necrosis. Carboxyatractyloside also failed to cause liver necrosis. This indicated that there may be at least two toxins contained in the rootstock of Callilepsis laureola, one causing the liver lesion and the other (atractyloside) causing nephrotoxicity and hypoglycaemia. Repeated attempts at isolating the hepatotoxin have failed; the liver toxin or toxins being lost during the process of extraction and purification. Identification of the hepatotoxin awaits further investigation. It is possible that the liver necrosis may be caused by a metabolite or that it may be a synergistic effect of two or more compounds.
A quantification of heat load as assessed by indicators of tissue damage in rats.
(1984) Manjoo, Mahomed.; Burger, F. J.; Kielblock, Artz Johan.
Heatstroke is an illness that occurs when body temperature is grossly elevated, causing widespread tissue damage. The extent of tissue damage depends on the level of body temperature elevation and the duration. Despite the fact that the diagnosis of heatstroke is based on sound scientific principles, namely the elevation of serum enzyme levels as indicators of tissue damage, the sensitivity of these parameters of tissue damage in the prodromal period of heatstroke is less well established, especially for sub-lethal stress conditions. Furthermore, it is not known to what extent given elevations in serum enzyme levels reflect the nature of various combinations of hyperthermia and its duration as sustained during the prodromal period. In an attempt to throw some light on the questions posed above anaesthetized rats were exposed to three different sets of thermal conditions. However, the amount of heat gained over and above baseline levels was controlled to a 20% rise irrespective of the experimental conditions. Above this increment animals did not survive thus indicating excessive stress. Plasma enzyme levels were assayed in each group of animals upon termination of stress, six hours post-stress and 24 hours post-stress in order to investigate the patterns of enzyme release as well as the sensitivity of the respective indicators of tissue damage. On the basis of plasma enzyme assays, the tissue damage sustained during these particular experimental conditions was mild to moderate, completely reversible, not indicative of heatstroke but merely of generalized tissue damage. The results suggest that in addition to the established positive relationship between the level and duration of hyperthermia and tissue damage, a third component,namely the rate of rise in body temperature, nay constitute an important factor in the ultirrate pathology. In this regard, i.e. sub-lethal stress, creatine kinase proved to be the most sensitive and, therefore, the most useful parameter of tissue damage.
Morphology, membrane characterization and detection of a bacterium associated with ratoon stunting disease of sugarcane.
(1984) Pillay, Dorsamy.; Roth, G.; Oellermann, Rolf Alfred.
Ratoon stunting disease (RSD) of sugarcane was first recognized in 1944 in Queensland, Australia (Steindl, 1961). The disease occurs worldwide and causes significant yield losses, especially during drought. RSD produces no external symptoms except a non-specific stunting (Steindl, 1961). RSD, which was first recorded 1n South Africa in 1953 (Anon., 1960), causes a greater overall loss in yield than any other sugarcane disease in South Africa. Yields of sugarcane are reduced by 20% to 40% and the harvest of affected fields declines progressively with successive ratoons (Anon., 1980b). A virus was originally thought to cause RSD, but in 1973, a coryneform bacterium was implicated as the causal agent (Gillaspie et al., 1973; Teakle et al., 1973). In 1980, our laboratory reported the successful isolation and culture of a coryneform bacterium associated with RSD of sugarcane and was indicated to be the causal agent (Nayiager et al., 1980). The lack of a rapid diagnostic technique applicable to mass screening of sugarcane has hindered progress in the control of the disease. There are two types of commonly used diagnostic tests. One test depends on the evaluation of internal stalk symptoms which may require from two to twenty six weeks to develop (Gillaspie et al., 1966; Matsuoka, 1971; Schexnayder, 1960; Singh, 1969). However, these symptoms are not always present in RSD affected plants and similar symptoms can sometimes result from other causes (Steindl, 1961). The other test involves establishing the presence of the coryneform bacterium associated with diseased plants. The bacterium is visible under high magnification by phase-contrast microscopy (Gillaspie et al., 1973) or by electron microscopy (Teakle et al., 1973). Although identification by the latter methods requires little time, the technology involved severely limits the number of samples that can be examined. Recently, serological techniques have been used (Brlansky et al., 1982; Damann et al., 1977; Davis et al., 1980; Gillaspie, 1978b; Gillaspie et al., 1979; Harris and Gillaspie, 1978) but their success has been limited. Besides problems with diagnosis of the disease, the precise morphology and taxonomy of the causal organism is unclarified. The objectives of this research programme were, firstly, to characterize the cultured intact bacterium and its constituent membranes both ultrastructurally and immunologically, and secondly, to evaluate various immunological methods for detection of the bacterium. This study should contribute to enhancing the taxonomic status of the bacterium and to the use of a rapid diagnostic technique applicable to mass screening of sugarcane. Such a technique should eventually contribute to effective control of RSD.
Studies on insulin secretion and insulin resistance in non-insulin- dependent diabetes in young Indians.
(1986) Naidoo, Chitraleka.
No abstract available.
The application of DNA hybridisation methods to a determination of the association of hepatitis B virus with cirrhosis and hepatoma.
(1987) Nair, Shamila.; Windsor, Isobel M.; Van den Ende, Jan.
Autopsy liver material from patients having died of chronic liver disease, cirrhosis, hepatocellular carcinoma (HCC) and causes unrelated to liver diseases was examined by dot blot hybridisation for the presence of HBV DNA. The results indicate that of the patients with chronic liver disease 6/9 were positive for HBV DNA in the liver tissue; of the patients with HCC 3/4 were positive for HBV DNA; of the patients with cirrhosis 4/4 showed the presence of HBV DNA in the liver. Thus by this technique 13/17 (76%) of these patients, all of whom were HBsAg positive, were shown to have HBV DNA present in liver tissue. However, autopsy liver samples were found to be unsuitable for Southern blot hybridisation. Biopsy liver/tumour tissue was examined for the presence of integrated or non-integrated HBV DNA by Southern blot analysis using the enzymes Eco R1 and Hind 111. 5/5 patients who were both HBsAg and HBeAg positive had extrachromosomal HBV DNA and 2/5 also showed the presence of integrated HBV DNA. 3/4 patients who were HBsAg positive and HBeAg negative had extrachromosomal HBV DNA and all three also had integrated HBV DNA. One control patient was negative for both markers and also for Southern blot hybridisation with the HBV DNA probe. These results support the hypothesis that HBV is a factor in the development of HCC, and indicate that the dot blot hybridisation method would be suitable for routine evaluation of patients with chronic liver disease or cirrhosis.
Control of prostaglandin biosynthesis by the intrauterine tissues in primary dysfunctional human labour.
(1987) Reddi, Kogie.; Norman, R. J.
No abstract available.
Evaluation of laboratory methods for susceptibility testing of staphylococcus aureus.
(1988) Jansen van Rensburg, Hermanus Christoffel.
The susceptibility of 80 StaphyIococcus aureus isolated to oxacillin was investigated using microtitre, agar dilution and Stokes' disc diffusion methods. There was a bimodal distribution of the isolates according to the oxacillin minimum inhibitory concentration (MIC) values. For the sensitive isolates, the agar dilution method generally gave lower MIC values than the microtitre method, while for the resistant isolates the agar dilution method gave comparable to slightly lower MIC values than the microtitre method. The Stokes disc diffusion method yielding the best results when performed on Mueller-Hinton agar incubated at 30°C for 18 hours; however local strains grew poorly when incubated at 30 C for 18 hours. The next best medium which provided clear disc diffusion results plus good growth was Mueller-Hinton agar incubated at 35°C for 18 hours, on which 10 % of the sensitive isolates appeared intermediate in susceptibility, and none resistant, while all the resistant isolates (microtitre MIC >8mg/1) appeared resistant. Oxacillin resistance among strains of Staphylococcus aureus tested by Stokes' disc diffusion method correlated best with gentamicin resistance, and less often with tetracycline resistance. Therefore gentamicin- or tetracycline-resistance may indicate oxacillin resistance in Staphylococcus aureus.
A study of the prevalence of campylobacter pylori in patients with upper gastrointestinal symptoms, and an evaluation of various laboratory methods to detect its presence.
(1988) Miller, N. M.; Van den Ende, Jan.
Antral mucosal biopsies were examined microbiologically and histologically for the presence of Campylobacter pylori in 224 patients with upper gastrointestinal symptoms. One hundred and eighty three (83%) patients were found to harbour Campylobacter pylori in their gastric mucosa. Campylobacter pylori was strongly associated with the presence of histological gastritis (93%) and was detected in only 10% of 30 patients whose gastric biopsies showed normal histology. Endoscopically diagnosed duodenal lesions were more strongly associated with the presence of Campylobacter pylori than were gastric lesions (p<0.001). A variety of laboratory methods were evaluated to determine the sensitivity and specificity to detect the presence of Campylobacter pylori. Histology was the most sensitive and specific method to detect the presence of Campylobacter pylori. Although culture was highly specific, it was less sensitive than histology in detecting Campylobacter pylori in gastric antral mucosal specimens. The "conventional" gastric urease assay, although specific, needs be performed under controlled conditions (37°C) for optimal results. The "one-minute" urease assay was more sensitive than the "conventional" gastric urease assays and was highly specific. ELISA to detect specific-IgG antibodies to Campylobacter pylori was a moderately sensitive non-invasive method to detect Campylobacter pylori infection, but was non-specific.
Characteristics of insulin receptors in a human lymphoblastoid cell line (Raji).
(1988) Dunn, Rosanne Dorothy.
The notion that insulin binds to a specific site on the cell membrane was first proposed many years ago. However, experimental proof of a membrane bound insulin receptor did not come until the early 1970s when biologically active radiolabelled insulin was used in direct binding studies (Cuatrecasas, 1971). Recent advances in understanding the mechanism of insulin action are the result of studies on the structure and function of the insulin receptor. The membrane receptor would appear to have two functions: firstly, it must bind insulin and secondly, it must couple insulin binding to insulin action. Defects in either of these receptor functions will result in an impaired response to insulin, or insulin resistance (Taylor, 1985). Insulin resistance is a common disorder in a number of disease states in man. For example, non-insulin-dependent diabetes mellitus and obesity are associated with mild insulin resistance (Bar et aZ., 1976). There are also a number of relatively rare syndromes of extreme insulin resistance in which there is either impaired receptor function, or an immunological defect resulting in the development of auto-antibodies against the insulin receptor (Taylor et aZ., 1985).Studies on insulin receptor defects associated with these disease states have led to progress in understanding the molecular mechanisms of insulin action. Ideally when investigating these disease states one should study insulin action on classical target cells such as adipocytes, hepatocytes or muscle. However, it is now well established that the kinetics of insulin binding to its membrane receptor is similar in all human tissue whether or not it is a target for insulin action. This has led to a great deal of research on the more accessible human tissues such as monocytes, erythrocytes, cultured fibroblasts and Epstein-Barr virus (EBV) transformed B-Iymphocytes. The most convenient tissue to study is EBV transformed B-Iymphocytes, as these cells can be taken from individual patients and grown in culture in large quantities, which facilitates biochemical studies. Despite these advantages, it is important to establish that this virus-induced receptor is a true insulin receptor and not an artifact of viral transformation. Studies on B-Iymphocyte proliferation have shown that the insulin receptor appears on the cell membrane during the proliferative phase of B-cell activation. However , this is a transient event and once the cell reaches maturation the insulin receptor is no longer evident (Marchalonis & Galbraith, 1987). The insulin receptor has also been demonstrated in a number of cultured human lymphoblastoid cell lines (Gavin et aL, 1983; Maegawa et aL, 1983). It seems, therefore, that the insulin receptor is normally expressed by blast cells. The purpose of this study was to investigate insulin binding characteristics on a human lymphoblastoid cell line with B-cell characteristics which was originally derived from a patient with Burkitt's lymphoma. These cells, which are known as Raji cells, are unusual in that they carry multiple copies of the EBV genome in their DNA. For this reason they provide a useful model system for studying the insulin receptor in EBV transformed lymphocytes. In addition, studies on the mechanism of insulin action in these cells should give some insight into the function of the insulin receptor during B-cell proliferation. In this study four major characteristics of insulin binding to insulin receptors on Raji cells are described. Firstly, on the basis of kinetic studies a model for insulin-receptor interaction was established. Secondly, processing of insulin and the receptor was investigated to determine whether the receptor is functional. A third aspect was elucidation of the receptor structure and the insulin binding site. Finally, the cross-reaction between insulin and type I IGF receptors was studied, and the cellular response mediated by the insulin receptor and growth factor receptor was determined.
The effect of vitamin B-6 deficiency on copper, zinc and iron balance in the rat.
(1988) Channa, Mahendra Lala.; Burger, F. J.
In order to address the contradictory reports on the rat trace element status during a vitamin 8-6 deficiency, Zn, Cu and Fe balance was assessed over 8 weeks in 3 groups of young male rats. Group 1 was the control group fed on a diet supplemented with 3,5 mg/kg of vitamin B-6. Group 2 was the marginally deficient group, fed a diet supplemented with 1,75 mg/kg of vitamin B-6 and Group 3 was the totally deficient group without any vitamin 8-6 in the diet. Diet, urine and fecal samples were analysed to determine the mean daily Zn, Cu and Fe balance for each group during each week of the study. Urinary xanthurenic acid (XA), plasma pyridoxal (PL), and plasma pyridoxal 5' -phosphate (PLP) were also analysed in order to determine the vitamin 8-6 nutritional status of each animal group. The totally deficient Group 3 showed decreased growth and food consumption when compared to the control and marginally deficient groups. There was a significant difference in XA excretion and plasma PLP and PL levels between all 3 groups with a progressive increase in XA excretion and a progressive decrease in PLP and PL levels from Group to Group 3. Although all groups were found to be in a positive balance for Zn, Cu and Fe, the totally deficient group was in a less positive balance compared to Groups 1 and 2. Furthermore, the percentage excretion of Zn and Cu, when compared to the intake, was greater in this group. This increased excretion, coupled with a decreased food intake, accounted for the lowered Zn and Cu balances in the totally deficient group. Fe excretion did not differ significantly between all 3 groups. The marginally deficient Group 2 showed no significant difference in growth, food consumption, trace element balance and excretion when compared to the control group, indicating the beneficial effects of even subminimal levels of vitamin B-6. This study confirms that the nutritional status of t~ace elements, especially that of Zn and CU, is related to the vitamin B-6 status of the animal.
Aspects of sexually transmitted diseases at King Edward VIII hospital.
(1988) Hoosen, Anwar Ahmed.; Van den Ende, Jan.
Abstract available in PDF.
Microbiology and molecular epidemiology of multiresistant haemophilus influenza type B in Durban, South Africa.
(1988) Peer, Abdool Kader Cassim.; Van den Ende, Jan.; Smith, Arnold L.; Ward, Joel I.
Microbiological and molecular epidemiological studies were conducted on 36 multi-resistant Haemophilus influenzae strains, isolated from paediatric patients, over a 26 month period (April 1986 to May 1988). The majority of strains (80,5%) had been isolated from blood and cerebrospinal fluid. More than 80% of isolates tested belonged to biotype II and 90% were of serotype B. Minimal inhibitory concentrations against 6 antibiotics (ampicillin, chloramphenicol, tetracycline, rifampicin, streptomycin and cefotaxime) confirmed the presence of multi-resistant strains. Resistance to rifampicin was confirmed in 6 (16,7%) strains. All strains were susceptible to cefotaxime. Ten transconjugants analysed with respect to their plasmid content were shown to harbour an identical 41 MDa plasmid. Restriction endonuclease digests of these plasmids with Eco R1 and Sst1 revealed almost identical restriction patterns. Outer membrane protein profiles of 19 strains revealed the predominance of one particular subtype. By combining the microbiological and molecular epidemiological findings, it is concluded that one strain of H. influenzae type b is responsible for the nosocomial acquisition of infections amongst paediatric patients. The implifications of these findings are discussed.
Endotoxaemia in intestinal dysfunction in experimental animals : intestinal ischaemia and hyperthermia.
(1988) Gathiram, Premjith.; Gaffin, Stephen L.
Endotoxins or lipopolysaccharides (LPS), highly toxic component of the outer membrane of gram-negative bacteria, are normally present in the mammalian gut lumen.In this thesis, I investigated, in laboratory animals, whether these gut-derived endotoxins play a role in pathophysiology resulting from intestinal dysfunctions caused by intestinal ischaemia and heat-stress.In primates, reperfusion of the splanchnic region after a temporary ischaemia was followed by a rapid increase in LPS concentration, first in the hepatic portal plasma and, ten minutes later, in the systemic arterial plasma. Rises in plasma LPS concentrations during or following the temporary intestinal ischaemia was prevented by prophylactic administrations of corticosteroids, anti-LPS IgG antibodies and oral, non-absorpable, antibiotics agents which appear to stabilize cellular membranes, aid the reticuloendothelial system in removal of LPS from the circulation and destroy the intestinal aerobic gramnegative bacteria respectively. In addition, administration of therapeutic anti-LPS antibodies also rapidly reduced the plasma LPS concentrations to baseline during an endotoxaemia. In a control heat-stress model, elevations in plasma LPS concentration commenced at rectal temperatures greater than 41,SoC. Like the intestinal ischaemia model, this occurred first in the hepatic portal plasma, and 10-15 minutes later, in the systemic arterial plasma. Peak plasma LPS levels of about 0,3 ng/ml, measured in heat-stressed primates, have proved in previous studies, to be toxic. A rapid decline in mean arterial pressure was followed by increases in plasma LPS concentrations and heart rates. Reductions in splanchnic blood flow and consequent local ischaemia coupled with thermal injury to the intestinal wall and the liver, may have permitted rises in plasma LPS concentration. Furthermore, as in the ischaemia model, prophylactic administrations of corticosteroids, anti-LPS IgG antibodies, and oral, nonabsorbable antibiotics prevented a rise in plasma LPS concentration. Of importance, prophylaxis with intravenous corticosteroids and 'anti-LPS IgG antibodies increased the survival rates significantly in heat stroke in primates. In addition, monkeys having high titres of "natural" antiLPS IgG antibodies had lower plasma LPS concentrations and survived the induced-heat stroke. It is suggested that other pathophysiologic conditions which compromise the integrity of the gut wall would also lead to the development of an endotoxaemia, and that gutderived endotoxins contribute to the athogenesis of heat stroke and treatments with corticosteroids and anti-LPS IgG antibodies may prove beneficial in other endotoxinrelated disorders.

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