Culture and sensitivity of mycobacterial isolates from cases of pulmonary tuberculosis classified as treatment failures in a teaching hospital.

BACKGROUND: The level of drug resistance in mycobacterial isolates from previously treated cases in Ghana is not known although drug resistant tuberculosis threatens efforts to control the disease. OBJECTIVE: To identify and determine the susceptibility of mycobacterial isolates from tuberculosis cases with clinical treatment failure. METHODS: This prospective survey was undertaken at the Chest Clinic of Korle Bu Teaching Hospital in Accra, Ghana. The participants were twenty-eight cases referred to the hospital with clinical treatment failure. Two sputum specimens from each case were stained by Ziehl-Neelsen method, cultured, identified and sensitivity tests performed by the proportion method. RESULTS: Eighteen isolates of mycobacteria were identified from 28 failed treatment cases. Five were atypical mycobacteria. Approximately fifty percent (13/28) of cases had Mycobacterium tuberculosis, 5(18%) had atypical mycobacteria, 7(25%) had pure fungal growth and 3(11% 8) had no growth. Fifteen isolates were resistant to two or more drugs, of which 6 were resistant to all four drugs tested. CONCLUSION: Continuous drug resistance monitoring must be instituted as part of the tuberculosis control programme.

Prevalence of human immunodeficiency virus infection among tuberculosis suspect patients in Accra, Ghana.

BACKGROUND: Acquired immunodeficiency syndrome is a major public health concern worldwide, particularly in Ghana, where recent reports indicate an increase of the disease. A close association between infection with human immunodeficiency virus (HIV) and tuberculosis (TB) is well known. A previous study showed a 16.8% seroprevalence of HIV in TB patients on admission at the chest clinic of the Korle-Bu teaching hospital. However this was in severely ill patients on admission and there was a likely selection bias. This study was therefore designed to determine the prevalence of HIV infection among patients suspected of TB attending the laboratory of the chest clinic of the Korle-Bu Teaching hospital, Accra, Ghana. METHODS: Pulmonary TB was diagnosed using clinical, sputum smear microscopy and chest x-ray features. HIV was determined using particle agglutination test (HIV-1 and HIV-2) and synthetic peptide-based immunoassay (Peptilav I and II ELISA). RESULTS: Of the 277 subjects examined, 108 (39%) were diagnosed as TB. The seroprevalence of HIV was 46.2% in all TB suspect patients. It was 47.2% and 45.6% in those with and without tuberculosis, respectively. in both groups, the peak age distribution of subjects positive for HIV antibodies was from 20 to 59 years. CONCLUSION: The results show a great increase in HIV seroprevalence in TB patients in Korle-Bu. The high HIV seroprevalence suggests that subjects suspected of TB should be tested for HIV as well.

Adult tetanus in Accra, why the high mortality? An audit of clinical management of tetanus.

BACKGROUND: Tetanus is a life threatening infection relatively uncommon in the developed countries but occurs frequently in developing countries with case fatality rates of 40-60 %. Recent review of adult tetanus at the Korle-bu Teaching Hospital showed a high case fatality of 50%. In order to determine the factors underlying this high case fatality we conducted a retrospective clinical audit of the clinical management of adult tetanus admitted in 1994 to 2001 to the Korle-bu Teaching Hospital. METHODS: Data extracted from the admission and discharge books of the Fevers' Unit of Korle-bu Teaching Hospital, Accra and patient case notes were examined and analysed. RESULTS: Case fatality rate (CFR) varied from 25 % in 1999 to 72.7% in 2001. There was no gender difference in the case fatality. There was no significant difference in the mean age of those who died and those who survived, however, the CFR rose with age. The presence of neck and a dirty wound were associated with increased CFR. The CFR correlated with the severity of tetanus and increased when an expected treatment action, wound debridement, administration of antibiotics and/or immunoglobulin, was not performed. The administration of anti-tetanus toxin was associated with an increased CFR. CONCLUSION: The high case fatality rate in Accra was due to inappropriate management with most of the patients not treated with immunoglobulin and antibiotics and had inadequate wound care.

Blood pressure response to out-patient drug treatment of hypertension in 1973-1993 at Korle-Bu Teaching Hospital, Accra, Ghana.

A retrospective audit of the first twelve months of out patient drug treatment of hypertension at the Korle-Bu Teaching Hospital during the period 1973-1993 is reported. A previous study had shown that at least 7 drug regimes were used to treat hypertension at Korle-Bu during the period. The aim of the present study was to compare the effect and efficacy of these antihypertensive drug treatment regimes on blood pressure during the first 12 months of treatment. Result of 155 (47%) case notes, which met the inclusion criteria, are presented. One month of drug treatment of hypertension significantly reduced systolic and diastolic blood pressure by 21.4 +/- 30.5 (p<0.001) and 13.8 +/- 16.5 (p<0.001) mmHg, respectively. This reduction in blood pressure was maintained to the 12th month. At 12 months, systolic and diastolic blood pressures were unchanged in 19% and 28% of patients, respectively, indicating no response to drug treatment. Recommended target blood pressure of < or = 140/90 mm Hg was achieved in only 25.6% of all patients. All drug treatment regimes significantly reduced blood pressure to a similar extent so that any differences were not statistically significant. However, the efficacy of the drug regimes differed significantly (p=0.02). It was greatest in patients treated with monotherapy with either diuretic or reserpine, intermediate with two drug combinations and least with 3 or 4 drugs. The data showed that diuretics were marginally better than reserpine as first line monotherapy. Furthermore, any diuretic based 2-drug regime was equally efficacious although a beta-blocker or methyldopa as second drug seemed favoured by the data. The addition of a third or fourth drug was counter productive as the increased number of drugs did not decrease blood pressure significantly.

Characteristics of adult tetanus in Accra.

BACKGROUND: Tetanus is a life threatening infection with an estimated annual global incidence of about 1 million cases and a mortality of 50%. It is very common in developing countries. The prevalence in Ghana is not known, however, cases continue to be admitted in hospitals in the country. This retrospective study was undertaken to define the characteristics of cases of tetanus in adults admitted to the Korle-bu Teaching Hospital, Accra, Ghana, from 1 January 1994 to 31 December, 2001. METHODS: Information was extracted from the admission and discharge registers of the Isolation Unit of Korle-bu Teaching Hospital, Accra and case notes were examined and analysed. RESULTS: There were 158 (76.6%) males) cases of tetanus with mean age of 32.7 +/- 15.0 years. The peak age was in the 20-29 year group. Admission rate was lowest during the raining season months of June-August. Traumatic injury occurred outdoors (56.9%) and was caused by deep prick (24.3%), or cut (16.2%). The most common site of injury was on the lower (44.6%) limbs. The time interval between injury and admission was 8.3 +/- 22.4 weeks (range 1-156 weeks) and the duration of symptoms was 2.9 +/- 2.7 days (range 1.0-21.0 days). The most common presenting features were locked jaw (82.4%), general spasm (62.2%), presence of a wound (53.7%) and neck stiffness (50.0%). Hospital admission was 11.4 +/- 11.6 (range 0-53) days. The case mortality was 50% (79/158). CONCLUSION: These results confirm that adult tetanus is still very prevalent in Ghana and is occurring in a younger age group compared to that in the developed countries. The case mortality is still very high.

Prenatal transmission and pathogenicity of endogenous ecotropic murine leukemia virus Akv.

OBJECTIVE: Mouse strains carrying endogenous ecotropic murine leukemia viruses (MuLV) are capable of expressing infective virus throughout life. Risk of transplacental transmission of MuLV raises concerns of embryo infection and induction of pathogenic effects, and postnatal MuLV infection may lead to tumorigenesis. METHODS: Endogenous ecotropic MuLV-negative SWR/J embryos were implanted into Akv-infected viremic SWR/J mice, into spontaneously provirus-expressing AKR/J mice, and into noninfected SWR/J control mice; virus integration and virus expression were investigated at 14 days' gestation. Tumor development was monitored over 18 months. RESULTS: Of 111 embryos, 20 (18%) recovered from Akv-infected SWR/J mice, which had developed normally, were infected. New proviruses were detected in 10 of 111 (9%) embryos from Akv-infected SWR/J mice, and in 2 of 60 (3%) embryos from AKR/J mice; none expressed viral protein. Of 127 embryos recovered from Akv-infected SWR/J mice, 16 (13%) were dead; 4 of 5 (80%) were infected and expressed viral protein. Of 71 embryos from AKR/J mice, 11 (15%) were dead, and 2 of 2 had virus integration; virus expression was not detected. Numbers of dead embryos recovered from experimentally infected, viremic SWR/J mice and from spontaneously endogenous MuLV-expressing AKR/J mice were significantly higher, compared with numbers from nonviremic SWR/J control mice, and embryo lethality was significantly associated with prenatal provirus expression. Postnatal inoculation of Akv induced lymphoblastic lymphomas in 15 of 24 (61%) SWR/J mice within mean +/- SD latency of 14 +/- 2.4 months. Only 3 of 39 (8%) control mice developed lymphomas (P < 0.005). CONCLUSION: Embryos in MuLV-viremic dams are readily infected, and inappropriate prenatal expression of leukemogenic endogenous retroviruses may play a critical role in embryo lethality and decreased breeding performance in ecotropic provirus-positive mouse strains.

[New paths for Internet generated learning in anatomy]. / Neue Wege der Internet-gestützten Lehre in der Anatomie.

For the purposes of a functioning information and knowledge based medicine the conditions for the medical education are crucial. Although multimedia based courses and tutorials via the Internet seem to serve best for a more effective teaching and new didactics, respective anatomical offers in Germany are scarce and thus practice and experience are limited. Only simple digital equivalents of conventional contents and methods can be found, whereas the potencies of the new media are not realized in didactic concepts. Substantial advantages of web based tutorial systems are an intensive use of the feedback possibilities, the opportunity for continuous updating of the contents, the favourable distribution, and faster utilization of improved techniques. This paper introduces the adaptation of different techniques and the development of concepts and notions of modern Internet based teaching by the way of three different events in anatomical education for medical students and doctors. HistoNet 2000 was developed as an interface of lectures, seminars and practical courses in microscopy. The online transmission of a microscopical course as an interactive practical teleteaching was performed by the way of asymmetric data transfer via the ADSL-technology. Multicasting was used as well and has also been applied for the third project. In this multimedial online teaching different specialties were joined together for interdisciplinary courses via the Internet. These new technologies lead to enhanced efficiency in teaching and enlarge the educational offer. Specific Internet adapted teaching and learning projects have to be developed.

Impairment of renal sodium excretion in tropical residents--phenomenological analysis.

There is evidence of impaired renal sodium excretion in salt-sensitive African Blacks. A decreased rate of renal sodium chloride (NaCl) excretion, low plasma renin activity and a tendency to elevated blood pressure are the hallmarks of salt sensitivity. Recent evidence indicates that increased proximal and distal tubular fluid reabsorption in some tropical residents may explain the impaired sodium excretion in these people. In this study of a cohort population, we speculated that subjects selected from that population might be salt-sensitive. We therefore measured the sodium balance in 10 normotensive male subjects over 10 consecutive days, after they had ingested a normal or a high amount of sodium, as NaCl (salt) in their diet. We quantified their renal sodium excretion rate by phenomenological analysis of their sodium balance data. We also measured plasma renin activity for 7 consecutive days in a separate group of 6 male and 4 female subjects in order to assess the state of their renin/angiotensin system. We selected all our subjects from a cohort population of 269 subjects randomly selected from a community known to have a high prevalence of primary hypertension. Our data on two separate groups of subjects from the same cohort population revealed delayed renal sodium excretion with t1/2 of about 5 days, compared to published data for normal individuals with t1/2 of less than 24 h. Also, plasma renin activity levels were low. Hence, our subjects are salt-sensitive. Quantification of their renal impairment is important for various reasons: it heightens one's appreciation of the problem of salt retention in African Blacks who are salt-sensitive and it also underlines the importance of the need for further research into the benefits of dietary salt restriction for reducing cardiovascular mortality in African populations, as has been done in some Western countries.

Pattern of out-patient drug treatment of hypertension in Korle-Bu Teaching Hospital, Accra.

In a retrospective study of the pattern of drugs used in the initial treatment of hypertension, 300 case notes of hypertensive patients attending medical clinics at the Korle-Bu Teaching Hospital, Accra and whose treatment were initiated during the period 1973-1993, were reviewed. The mean age of patients was 55 years, mean pre-treatment systolic and diastolic pressures were 179.5 +/- 25. 5 and 108.5 +/- 14.2 mm Hg, respectively, with 85% of patients being female. The frequencies of individual drugs prescribed for the initial treatment of hypertension were: diuretics (90%), reserpine (46%), methyldopa (31%), and propranolol (30%). Single drug treatment was prescribed for 18%, two drugs for 60% and three or more (multiple drugs) for 22% of patients. The mean number of drugs per patient was 2.2 Patients prescribed multiple drugs had pre-treatment systolic and diastolic blood pressures which were significantly (p < 0.01) higher than those prescribed 2 drugs which were, in turn, higher (p < 0.001) than those prescribed single drugs. The results showed that during the period 1973-1993, diuretic based "stepped care" therapy was the main first line anti-hypertensive drug management regime. "Old" anti-hypertensive drugs were more commonly used than newer ones. The cost and availability drugs and the pretreatment blood pressure were probably the main determinants of the choice of the type and number of drugs prescribed.

Increasing the yield of harvested bone marrow cells by raising room temperature during marrow collection.

The time it takes to harvest bone marrow before transplantation could be reduced significantly by increasing the temperature of the operating room by 8-10 degrees C, to about 28-30 degrees C. In healthy donors, the collected volume of marrow was increased from 22.45 to 36.31 mL/min; in patients who received chemotherapy previously, from 21.67 to 29.98 mL/min. The time to collect a volume of 1200 mL marrow could be reduced significantly, from 57.78 to 38.25 minutes in healthy donors and from 71.07 to 43.36 minutes in patients who received chemotherapy previously, without any loss of quality of the sampled marrow. Operation time and thereby time of anesthesia could be reduced significantly by heating the operating room to a temperature of 28-30 degrees C. Harvesting at higher room temperature did not result in any adverse side effects for the patients. The procedure to increase the body temperature could be simplified by using electric blankets and aluminum foils for wrapping to avoid heat emission.

Knowledge of asthma and its management in newly qualified doctors in Accra, Ghana.

This study assessed first-year doctors' (House Officers) knowledge of asthma at the Korle-Bu Teaching Hospital. Seventy-two out of 80 doctors answered 32 questions on various aspects of asthma. Many of these doctors managed between one to three asthmatics per week. Few, however, did so by acceptable standards. In assessing the severity of asthma, 88% looked for cyanosis, 69% looked for pulsus paradoxicus and 63% looked for a fast pulse rate. Only 63% considered the measurement of peak expiratory flow useful. Ninety-four percent used intravenous aminophylline, 82% intravenous hydrocortisone and 74% oxygen as the drug of choice for acute severe asthma. In moderate forms of acute asthma, 54% used salbutamol inhaler or intravenous aminophylline, 28% oxygen, 15% steroid inhaler and 14% oral prednisolone. Nebulized bronchodilators are not well known for use in either severe or moderate asthma and only 19-21% of doctors had prescribed their use. In chronic asthma, 55-65% of respondents prescribed bronchodilators compared to 19-35% who gave anti-inflammatory drugs. These results reveal insufficient knowledge of the pathophysiology of asthma, the use of standard drugs in asthma therapy and international guidelines for the management of asthma. The results also show that the pragmatic constraints which exist in developing countries preclude the adoption of international guidelines without local modification.

A comparative study of isradipine and nifedipine in the monotherapy of mild to moderate hypertension in the Ghanaian

Clinical experience with the new dihydropyridine calcium antagonist; isradipine; is reported. Isradipine was compared with nifedipine in a multicentre open; parallel group; clinical therapeutic trial involving 70 patients with mild to moderate hypertension. A four week placebo washout period was followed by a 12 week active treatment period during which patients were randomized to receive either 2.5mg isradipine twice daily (n=40) or 10mg nifedipine three times daily (n=30). Isradipine significantly reduced sitting systolic/diastolic blood pressures from 176.7+/-21.0/106.7+/-7.0mmHg to 142.9+/-15/93.1+/-7.7mmHg (p0.001) at the end of 12 weeks. Similarly; nifedipine reduced sitting systolic/diastolic blood pressures from 170.1+/-19.5/106.2+/-7.4mmHg to 139.1+/-9.7/92.1+/-7.8mmHg (p0.001). Normalisation (diastolic 90mmHg) rates were 67 per cent and 60 per cent for isradipine and nifedipine respectively while good response (diastolic fall 10mmHg) rate was over 85 per cent on either drug. Heart rate did not significantly change with either treatment. Three (3) patients taking isradipine experienced headache and 7 patients taking nifedipine had drug related adverse effects (5 had headache; 1 insomnia and 1 first dose hypotension). Therapy was withdrawn in 4 patients taking nifedipine and 1 taking isradipine. It is concluded that isradipine is comparable to nifedipine and is an effective and well tolerated antihypertensive agent in the Ghanaian

[Morphologic changes in the early stages of arthrosis]. / Morphologische Veränderungen in frühen Stadien der Arthrose.

"Joint failure" may be the result of different pathological conditions. While in some arthropathies initial changes prior to secondary cartilage destruction may be observed morphologically, the early changes in "mechanically induced" osteoarthrosis are not well known. In the present paper the ultrastructural events, eventually leading to osteoarthrotic cartilage destruction are presented. From the morphological changes it is assumed that the primary lesion leading to cartilage destruction may be seen in the loss of the granular surface microstructures of cartilage that may be followed by an increased hydration and thereafter chondrocytic death with destruction of cartilaginous matrix.

The occurrence of elastic system fibres in the matrix of normal articular cartilage.

Normal articular cartilages from the weight-bearing areas of the femoral condyles of the knee joints of 11 patients (3-20 years old) and of 35 Schwarzkopf sheep (3 months to 2 years old) were studied using the electron microscope. The study has shown that the matrix of normal articular cartilage is not only composed of collagen fibrils and proteoglycans, but also contains two types of elastic system fibres. Small elastic fibres can be identified in the superficial and lower radiate zones of cartilage of man and sheep. Similar to elastic fibres in other tissues, they consist of a central amorphous core and are surrounded by aggregates of 10 nm microfibrils. Another type of elastic system fibres, oxytalan fibres, are found in the intermediate and upper radiate zones of the articular cartilage.

The role of alpha-adrenoceptors in the regulation of renal tubular sodium reabsorption and renin secretion in the rabbit.

A study was undertaken in the anaesthetized rabbit to classify the alpha-adrenoceptor subtypes responsible for increasing renal tubular sodium reabsorption and renin secretion. Intrarenal administration of noradrenaline, at doses which did not change renal blood flow or glomerular filtration rate, significantly decreased urine flow, absolute and fractional sodium excretion by between 26% and 29%. These renal responses to noradrenaline were abolished by the selective alpha 1-adrenoceptor antagonist, prazosin, but not by the selective alpha 2-adrenoceptor antagonist, idazoxan. Noradrenaline, given intrarenally, increased renin secretion between two and three fold and this response was not modified by either prazosin or idazoxan. Intrarenal administration of the selective alpha-adrenoceptor agonists, phenylephrine and methoxamine, at dose rates which did not change renal haemodynamics, significantly reduced urine flow, absolute and fractional sodium excretion by 15% to 33%, but at doses which reduced blood flow and filtration rate, by between 11% and 26%, urine flow, absolute and fractional sodium excretion decreased between 42% and 49%. Infusion of guanabenz (selective alpha 2-adrenoceptor agonist), at doses with no renal haemodynamic action, increased urine flow, absolute and fractional sodium excretion by 11% to 15%, while at doses which decreased blood flow by 7%, these other variables did not change. Administration of UK 14304 (selective alpha 2-adrenoceptor agonist) reduced blood flow and filtration rate by 3% and 9% respectively but had no other measurable action. At higher doses, which decreased blood flow by 14% and filtration rate by 24%, urine flow, absolute and fractional sodium excretion fell by between 27% and 50%. Renin secretion was significantly increased by the high doses of phenylephrine and UK 14304 but not by the low doses of these drugs. These studies show that adrenergic stimulation of renal tubular sodium reabsorption involves the activation of alpha 1- but not alpha 2-adrenoceptors. Further, adrenergic activation of the juxtaglomerular cells to release renin does not appear to involve either alpha 1- or alpha 2-adrenoceptors.

An in vivo study of the alpha-adrenoreceptor subtypes on the renal vasculature of the anaesthetized rabbit.

An attempt has been made to classify the subtypes of alpha-adrenoreceptors mediating renal vasoconstriction in vivo using renal nerve stimulation and alpha-adrenoreceptor agonists and antagonists of varying selectivity in anesthetised rabbits. In the first series of experiments prazosin more potently inhibited the phenylephrine than the nerve induced renal vasoconstriction while phentolamine inhibited the response to phenylephrine and nerve stimulation nearly equally. In the second series of experiments low to moderate doses of yohimbine potently inhibited the renal vasoconstriction of clonidine, was less potent on that induced by noradrenaline and did not significantly affect that of phenylephrine. Prazosin was a potent antagonist of phenylephrine induced vasoconstriction but was less potent on nerve stimulation and noradrenaline, and was without effect on clonidine. In the third series of experiments, prazosin partially inhibited the renal vasoconstriction produced by all frequencies of nerve stimulation and that produced by high doses of noradrenaline. The prazosin resistant component of nerve stimulation and exogenous noradrenaline was significantly reduced by the addition of yohimbine. These results have been taken to suggest the presence of both alpha 1- and alpha 2-adrenoreceptors in the renal vasculature of the rabbit which mediate the renal vasoconstriction of exogenous and endogenous noradrenaline. They further show that in the rabbit the alpha 2-adrenoreceptors mediate a much greater proportion of the total renal vasoconstriction compared with the dog, cat or rat in which the alpha 1-adrenoreceptor population appears to be the predominant receptor.

The subtype of alpha-adrenoceptor involved in the neural control of renal tubular sodium reabsorption in the rabbit.

A study was undertaken in pentobarbitone anaesthetized rabbits, undergoing a saline diuresis, to determine the subtype of alpha-adrenoceptor mediating renal tubular sodium reabsorption. Stimulation of the renal nerves at low rates, to cause an 11% fall in renal blood flow, did not change glomerular filtration rate but significantly reduced urine flow rate, and absolute and fractional sodium excretions by approximately 40%. These responses were reproducible in different groups of animals and with time. Renal nerve stimulation during an intra-renal arterial infusion of prazosin, to block alpha 1-adrenoceptors, had no effect on the renal haemodynamic response but completely abolished the reductions in urine flow rate, and absolute and fractional sodium excretion. During intra-renal arterial infusion of yohimbine, to block renal alpha 2-adrenoceptors, stimulation of the renal nerves to cause similar renal haemodynamic changes resulted in significantly larger reductions in urine flow rate, and absolute and fractional sodium excretion of about 52-58%. These results indicate that in the rabbit alpha 1-adrenoceptors are present on the renal tubules, which mediate the increase in sodium reabsorption caused by renal nerve stimulation. They further suggest the presence of presynaptic alpha 2-adrenoceptors on those nerves innervating the renal tubules.

The effect of graded renal nerve stimulation on renal function in the anaesthetized rabbit.

The renal nerves of the rabbit were stimulated to cause less than 5, 9 or 22% reduction in renal blood flow. Glomerular filtration rate was reduced by 0, 3 and 11% respectively when the renal nerves were stimulated at these increasing rates. At low and moderate rates of renal nerve stimulation absolute and fractional sodium excretions were reduced by between 17 and 22%, but at the highest rates they were reduced by 55 and 53% respectively. At increasing rates of renal nerve stimulation plasma renin activity was increased by 40, 70 and 180%.