Medical Research in Zambia |
The thesis examines whether or not adding an isometric component in form of natural day to day weight carrying by hand, to dynamic walking exercise augments the increases in heart rate and arterial blood pressure and whether or not this would lead to a greater and an earlier onset of ST segment depression. A preliminary trial was also undertaken to explore the use of the effect of combined exercise in detecting significant coronary artery disease. The objective of is to find out a practical and a natural means of performing isometric exercise such as carrying weight by hand at rest and examine its effects. The examined isometric effort have been used to test whether or not adding this isometric effort ( natural hand carrying of weights ) to dynamic walking exercise augments the increases in heart rate and arterial blood pressure in normal subjects and in patients with ischaemic heart disease.Finally, the combined exercise test has been explored in a preliminary trial in respect of its feasibility and ability to test significant coronary artery disease.The researcher concludes by confirming that the preliminary trial which showed in a subset of patients who had coronary angiography that combined isometric and dynamic exercise augmented the responses of an increase in heart rate, systolic and diastolic blood pressure and ST segment depression also showed that the results of exercise testing can be improved. The combined test reduced the number of inconclusive tests by more than 50%, improved negative predicted value of the dynamic test by 23% and increased test sensitivity by 13%. These changes were related to achieving greater haemodynamic responses and ST segment depression within the time limit of exercising. These results may be taken further in a larger study on patients with suspected ischaemic heart disease, particularly to solve the problem of inconclusive test outcome. The study establishes that adding a normal form of isometric effort to the dynamic walking exercise augments the increases in haemodynamic variables, total body oxygen consumption and possibly augmentation of myocardial oxygen consumption. This augmentation leads to an earlier and greater manifestation of features of myocardial ischaemia.
- Background:
Repeated short periods of coronary ischaemia protect the myocardium against subsequent sustained ischaemia. This phenomenon, termed ischaemic preconditioning, has been seen to be protective not only against myocardial necrosis but also against ischaemia/ reperfusion arrhymias, post-ischaemic contractile dysfunction “ stunning “ and abnormalities in myocardial perfusion. This protection has been seen to be biphasic. The “ classical “ protection is evident within 5 minutes of reperfusion but is transient and disappears within 1- 2 hours. However, it has been observed that 24 hours later there is , again, enhanced protection against sustained ischaemia ( the “ second window of protection “ ). The time course of this delayed phase of myocardial protection is undetermined and so is/ are the mechanism ( s ) underlying it. Protection Kinase C has been shown to be in the “classical “ protection and is thought to vital in the mechanisms underlying the protection mediated by preconditioning.- Aims:
The aims of this study were to characterise the time course and to investigate the role of protein Kinase C in signal transduction of the delayed phase of myocardial protection after ischaemic preconditioning.- Methods:
Male New Zealand White rabbits were used . The experiments were in two parats; Part 1: preparation and pretreatment experiments and part 2: infarction and infarct size assessment . The rabbits were assigned to 2 groups. One group was subjected to four 5-minute occlusions separated by 10 minutes of reperfusion while the other was sham operated. They were left to recover for 24,48,72 and 96 hours before being subjected to the 30 minutes sustained ischaemia and 120 minutes of reperfusion. The infarct was assessed by tetrazolium chloride staining. 2 additional groups were included in the 24 hours recovery study . While one group was preconditioned and the other sham operated, they were both given 5 mg/kg chelerythrine chloride 10 minutes before either treatment. Results: There were hardly any differences in haemodynamic variables between the groups and the volume of myocardium at risk of infarction were similar among the groups. The Infarct/Risk ratios are tabulated bellow:
*p<0.05
24 hours 48 hours 72 hours 96 hours Chel treated PC 31.3+4.1* 19.6+6.3** 16.1+2.9** 37.4+4.7 61.6+5.2 SHAM 46.7+5.6 41.9+3.0 40.1+4.8 44.6+3.8 58.1+4.4
**<0.01 compared with sham( ANOVA at 24 hours and unpaired t-test at other time points ). PC= preconditioned group, Chel=chelerythrine.
- Conclusions:
The delayed phase of myocardial protection is evident 24 hours after ischaemic preconditioning, and seems to be enhanced at 48 hours. It persits through 72 hours but wanes and disppears by 96 hours. The protection is abolished 24 hours by chelerythrine, a more specific protein kinase C inhibitor, demonstrasting an involvement Protein Kinase C in the delayed phase of myocardial protection after preconditioning.
The study defines the relative frequency of rheumatic diseases in patients attending the University Teaching Hospital in Lusaka which functions as a primary care facility rather than its intended role of a tertiary referral hospital, these spectum of diseases may well be considered as a representative of true picture for Lusaka. The influence of HIV on the spectum of Rheumatic diorders at this institution is striking. The data contained in this study provides additional evidence for an association between HIV infection and the occurrence osf spondyoarthropathies in indigenous black Africans.
This disssertation is about a series of studies on the impact of Human Immunodeficiency Virus on tuberculosis which were carried out in Zambia between November 1988 and December 1991. Observations made in the 1980s suggested an association between tuberculosis and the Human Immunodeficiency Virus ( HIV ), consistent with the specific immune defects caused by HIV and with current understanding of the immunopathogenesis of tuberculosis.The scholar suggests that the impact of the association was likely to be greatest in countries where tuberculosis was already endemic. The claim is based on the hypothesis that a rise in incidence of reported cases of tuberculosis was seen in Zambia beggining in the mid 1980s coincident with expanding epidemic of HIV infection. The researcher reveals that three studies regarding the interaction between tuberculosis and HIV were undertaken based at the University Teaching Hospital in Lusaka, Zambia.A preliminary cross-sectional study indicates that three hundred and forty-six out-patients being treated for tuberculosis were screened for HIV-1 antibody: 206 ( 60% ) were HIV-1-positive. The highest number of cases, and the highest seroprevalence of HIV, were among women aged 14 to 25 and men aged 25 to 34 years. HIV prevalence was higher in patients with pleural disease ( 81% ) or percardial disease ( 84% ) than in those with confirmed pulmonary tuberculosis ( 49% ). Among culture-confirmed pulmonary cases, HIV infection was associated with negative sputum smear and with abscence of upper zone involvement or activities on chest x-ray. All of eight patients with a history of severe drug rash were HIV-positive.
A prospective cohort study, of a representative sample of previously untreated tuberculosis in Lusaka, to examine the effect of HIV on presentation and diagnosis of tuberculosis, response to treatment, mortality and recurrence rate. This study reports that findings at presentation were examined for 249 patients: 182 ( 73% ) were HIV- positive. The association of HIV with extrapulmonary tuberculosis( including pleural and pericadrdial disease ) was confirmed. Among culture-confirmed pulmonary cases the sputum smear was positive in 76% of HIV-negative,and 57% of HIV-positive, patients ( p=0.09 ). Radiological findings confirmed those of cross- sectional study. The tuberculin test was positive in 55% of HIV-negative and 27% of HIV-positive patients tested ( p<0.01 ).
Initial resitance to isoniazid was found in 5% of all cases with a positive culture. The research ends with the following conclusive remarks that the association between Myobacterium tuberculosis and the Human Immunodeficience virus is now beyond doubt. The impact of the dual epidemic of tuberculosis and Human Immunodeficience Virus is greatest in developing countries and , in parttcular, among young adults, who are of crucial social and economic importance. Compared with HIV-negative tuberculosis patients, a lower proportion of HIV-positive cases pulmonary disease, and those who do have pulmonary disease may be less infectious. This means that the rise in number of infectious cases caused by the epidemic of HIV infection may be les steep than the rise in the total number of tuberculosis cases, somewhat mitigating the effect of the dual epidemic on the general population. The application of fra fragment restriction length polymorphism analysis to Myobacterium tuberculosis may answer some outstanding epidemiological questions. In particular, it may be used to determine what proportion of new and recurrent cases of tuberculosis arise from endogenous reactivation, and what proportion from new infection, in the HIV-positive population in specific settings.
The diagnosis of HIV-associated tuberculosis is hampered by the low frequency of sputum smear positive cases, and by atypical radiological findings and anergy to tuberculin. The sputum remains specific for tuberculosis in countries like Zambia, but, in HIV-associated tuberculosis, is less sensitive. Serology and the polymerase chain reaction hold proomise for the development of new diagnostic tests. The recorded level of initial resitance to tuberculosis drugs in Lusaka was low in our study, but continuing surveillance for drug resistance is needed. Response to treatment for HIV-associated tuberculosis is good among surviving patients, but, under programme conditions in Lusaka there was a high mortality and a high recurrence rate. The outcome could be improved by promoting compliance with therapy, and possibly by selecting a more potent regimen. It is advocated that the use of thiacetazone be discontinued in areas where HIV is highly prevalent because of its association with severe cutaneous drug reactions. Adjunctive therapy with prednisolone in the treatment of tuberculosis was associated with increased incidence of Herpes zoster and Kaposi’s Sarcoma and should be further investigated in a controlled trial. Prophylactic chemotherapy for tuberculosis in individuals with HIV infection may have a role in a selected situations in developing, as well as develped countries. Its implementation should be studied in targeted groups, such has already screened for HIV infection within the AIDS Control Programme, or company employees.
Finally, the dual epidemic of tuberculosis and Human Immunodefiency Virus infection is a matter for global concern, calling for urgent intervetion at an international level. Improved implementation of current therapyfor tuberculosis must be achieved , bty ensuring a secuere drug supply, and by studing methods to promote compliance ( such as supervised, intermittent therapy ) in the context of individual communities. This must be combined with the development and application of new technology for epidemiology, and for the diagnosis and treatment of tuberculosis.
The study was done between April 1, 1993 to December 31, 1993. The major objective was to compare antemortem and post mortem diagnosis. Full autopsy was performed on 30 subjects out of 888 patients who died under the care of Unit I in the department of Medicine during the period of the study. The study results were influenced by 2 disease epidemics:- The HIV epidemic and an outbreak of meningococcal meningitis which followed a very severe drought described as the worst to have affected the Southern African region in 40 years. Basic laboratory work up was done in 12% of the cases. By comparing the antemortem, autopsy and the combined diagnosis it was possible to evaluate the contribution autopsy would have on improving the quality of clinical diagnosis for a physician working at the University Teaching Hospital. Atn the time of this study UTH lacked histopathology and sophisticated laboratory work up and clinical posmortem was not being regularly conducted at the hospital except for police cases.Although many minor discrepancies were noted, on comparing autopsy and antemortem diagnosis, a major discrepancy was considere as omission of the disease directly contributing to the cause of death. The study showed that 63.3% of diagnoses were in agreement. Sample size was not calculated before the sudy because there were no regular postmortems and no records of postmortems being done in 4 years preceding the study.
Major discrepancies were found as follows:
The study concludes that its findings of 63.3% overall agreement between antemortem and autopsy diagnosis are similar to literature results from elsewhere but the hospital should conduct regular autopsy in order to contribute to overall medical knowledge in the field of medicine.
- 25% in the central nervous system;
- 67% in the respiratory system;
- 40% in the cardiovascular system;
- 0% in the genito-urinary system;
- 33% Gastrointestinal and liver disease
- 50% miscellaneous diagnosis
The number of teaching staff at the hospital is small due to thye weak economy such that between admission and being seen by a senior registrar or consultant, there may be a time lag of between 4 hours and 72 hours. So the number of senior doctors also needs to be improved. The study sample was small ( 30 subjects ) the results of this study should be treated cautiously.
Discussion
A total number of 30 subjects were entered form a study population of 888 patients who died who died under the care of UNIT 1 in the department of Medicine. The rather small number studied was due the followoing factors:The researcher cautions that the sample size is inadequate and conclusions drawn from it may not be universally applicable.
- Many families did not consent for postmortem on religious grounds ( 80 cases ),
- Others did not consent on emotional grounds. Emotions were high in cases of families where family members had died of HIV infection which some family misconstrued was due to witchcraft this was in turn believed to be due to jealousy from neighbours who felt bad about the success of the family life ( 600 cases ).
- Others did not consent on grounds of distance between UTH and the village where the burial would take place ( 120 cases ) ,
- Day of week to bury- those wanted to bury during the weekend could not have postmortem done during the week because the mortuary would not keep bodies after postmortem ( 58 ).
Conclusion
In an analysis of 30 postmortems it was found that 63.3% of them there was agreement between antemortem and postmortem diagnosis. Agreement was highest in the nervous system and lowest in the respiratory system. Two cases of brain abscess needed special investigations with CT Scan. One case of nocardia brain abscess was found, this neurological diagnosis would be difficult to make life. The finding of norcardiasis brain abscess and pulmonary embolism is solitary and emphasises once again the need to do regular postmortem, “ Death is able to asist life, “ Virchoff.Inspite of the small sample size, certain perceptions have been confirmed in the study. The high incidence of HIV albet by clinical criteria, the high incidence of tuberculosis and the high incidence of HIV positive patients. An agreement rate of 63.3% is perhaps low ( between antemortem and postmortem diagnosis ). The mean length of stay of medical in patients has been estimated to be 4 days ( Bagshawe ) this is not long enough to evaluate fully these rather ill patients. From experience, at the time , it took at least 2-3 days for lab results of full blood count and chest radiology and 5-7 days to get AFB sputum results from the study, wen note that lab support existed in 12% of the patients. At 63.3% agreement rate, the performace of UTH met with Gresham and Turners estimates of reasonable quality of clinical diagnosis given the constraints.
A randomised placebo controlled double blind trial of two intermittent regimens of tuberculosis preventive therapy with a study sample of about 1000 HIV positive individuals was proposed as a collaborative effort between the University of Zambia and the London School of Hygiene and Tropical Medicine. Prior to begnning this study a pilot study was carried out in order to assess the feasibility of recruiting and following up a cohort of HIV positive individuals in Lusaka.At recruitment an assessment of knowledge and attitudes to HIV showed a high level of knowledge about HIV and its transmission. The recruitment of enffected patients occurred at a higher rate among those individuals already aware of their HIV status than those who were tested for the first time the purpose of recruitment into the study suggesting that a voluntary testing centre would a good recruitment site. Difficulty in excluding active tuberculosis was a majkor reason for no-enrolment into the study, however no active case of tuberculosis was diagnosed in these patients.
Tuberculin testing at the time of the initial HIV test showed a much lower frequency of positive tuberculin in the HIV positive tha the HIV negative subjects, indicating that tuberculin testing has limited usefulness as a means of identifying latent tuberculosis in areas with high rates of both tuberculosis and HIV.
Many of the students recruited did not return to the clinic for follow up. Some of the problems identified in the follow- up included difficulties in finding the patients within the community as a result of the wrong address being supplied, an inability to locate the given address in the residential areas and a tendency to easily move from one residential area to another. Thus it would be necessary to obtain very detailed information of the pateint’s residentila address as well as that of their next of kin in order to ensure adequate follow -up. More frequent reviews and repeated counselling might also contribute to better follow-up of asymptomatic patients.
Given the future impact that tyhe interaction with HIV was expected to have on the tuberculosis situation in countries like Zambia it was considered important to conduct a study to determine the efficacy of tuberculosis preventive therapy in this setting. The various problems identified during the pilot study indicated that implementation of relevant measures to ensure maximum follow-up of the patients would be critical.
Conclusion
HIV infection has become the strongest known risk factor for the progression of a latent tuberculosis infection into active disease. Isoniazid preventive therapy offers a possible therapeutic option for individuals found to be HIV positive in areas where the incidence of both tuberculosis and HIV is high and where it is not possible to use the currently available anti-retroviral agent. The major problems identified in the pilot study concernedboth the recruitment and follow-up of patients. Thus it would be important in the main study to ensure that detailed information of the addresses of the patient are obtained, including those of the next of kin at the time of recruitment. Repeated counselling to ensure that the patient undertakes the importance of attending the clinic and of informing staff in the clinic of any change in address may also help to improve follow-up of the patient.
This is a retrospective study of various aspects of menigitis in infancy and childhood presenting at the paediatric department of UTH over the period of 1st March 1986 to 28th Febraury 1987. 103 cases were recorded out of an annual admission of approximately 10,000 patients. Epidemiological features are discribed in relation to age, sex, monthly case incidence andmortality and relationship to local climate. The signs and symptoms have been compared with similar studies done by others in Zambia and in Africa and there does not seem to be much of a difference. The commonest pathogen isolated under 2 years was pneumococci while that isolated above 2 years was Nieserria meningitidis.Laboratory investigations like WBC, CSF, protein and glucose levels have been used for diagnostic purposes. Mortality rate was 27% and this was mainly because parents did not bring their children to hospital early enough for medical treatment. 23% of the children developed complications, the commonest being deafness, hydrocephalous, spasticity, hemiplegia and waekness.
Conclusion and Recommendations
Various aspects of meningitis in children coming to the University Teaching Hospital reveal the following:
- After 2 years the disease was more evenly distributed.
- The disease appears more in males than in females, though this has not been shown statistically.
- The causative organism varies with age Strephococcus pneumonae was more common below 2 years of age , while Neiserria menigitidis was common above 2 years .
- The prevelant organism for the period of study was pheumococcus.
- Both causative organism and the ralation of the disease to various areas are important in the control of the disease. Prevention of the disease is very important as the complication of the disease may be debilitating.
- Use of vaccines being explored could prove useful for the control of the disease .Health education with better standards of living too may prove of great help.
- A lumber puncture should be done on every child presenting with convulsions or suspecious of menigitis. This will help in the early detection and treatment of the disease.
- Laboratory results should be well presented as they could help in the treatment of the patient.
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Last updated February 19, 2001