IgE antibodies against penicillin as determined by Phadebas RAST

Serum samples from eighty-one patients with suspected penicillin allergy were investigated with Phadebas RAST using the penicillin derivatives Benzylpenicilloyl-human serum albumin (PBO-HSA) and Phenoxymethylpenicilloyl-human serum albumin (PMPO-HSA) and the results were compared with skin test results and clinical data. Of the sixty-one patients who had anaphylactic shock and/or urticaria as a possible consequence of penicillin administration, reagins against PBO-HSA and PMPO-HSA could be detected in thirty-four cases (56%). Five per cent of these patients, with positive RAST results, showed negative skin tests; in the other 95% both RAST and skin tests were positive. All, except eight, of the RAST-negative patients had had their adverse reactions at least 2 years prior to the blood sampling and in some of these cases skin tests were also negative. RAST and provocation test results agreed in 80% of the cases where exposition was performed. It is concluded that the RAST technique is a valuable diagnostic tool for the detection of immediate type hypersensitivity to penicillin.     

Age specific prevalence of impairment and disability relating to hemiplegic stroke in the Hai District of northern Tanzania. Adult Morbidity and Mortality Project

OBJECTIVES: To determine the age specific prevalence of impairment and disability relating to hemiplegic stroke in one rural area of Tanzania. METHODS: During the yearly house to house census of the study population of 148 135 (85 152 aged 15 and over) in August 1994, specific questions were asked to identify those who might be disabled from stroke. People thus identified were subsequently interviewed and examined by one investigator. In those in whom the clinical diagnosis of stroke was confirmed a more detailed interview and examination relating to risk factors and recovery was carried out. RESULTS: One hundred and eight patients, 61 men and 47 women, were identified with a median age of 70 (range 18-100). Median age at first stroke was 65 years. The age specific rates in this study were lower than previous studies in developed countries. All were cared for at home although 23 (21%) were bedbound. CONCLUSIONS: Although prevalence of impairment and disability related to stroke in this population as a whole was low this is mainly explained by the age structure, with less than 6% being aged 65 and over. Age standardised rates for stroke with residual disability were about half those found in previous studies in developed countries. Death from stroke in Africa may be higher but data are limited. With the demographic transition stroke is likely to become a more important cause of disability in sub-Saharan Africa.     

Effect of Caesalpina Bonducella Seeds on Blood Glucose in Rabbits

The seeds of Caesalpinia bonducella (L.) Flem. (Caesalpiniaceae) are sold in shops in Dar es Salaam, Tanzania, for the treatment of diabetes mellitus. A suspension of the powdered seed kernel in 0.5% carboxymethylcellulose (CMC) was tested for ability to lower blood glucose in fasted and glucose-fed normal albino rabbits. Following administration of 0.2, 0.4 and 0.8 g/kg body weight of the powder there was no difference in areas under the fasting blood glucose and oral glucose tolerance test (OGTT) curves as compared to controls given CMC (P > 0.05). Similarly, 0.2 g/kg body weight of the powder administered for 7 consecutive days had no effect on either fasting blood glucose or the clearance of a glucose load from the blood. However, 0.1 g/kg body weight chlorpropamide significantly decreased the area under the fasting blood glucose and OGTT curves as compared to controls given CMC (P = 0.05). Thus, contrary to a previous report, we could not detect any hypoglycaemic activity in the seeds of Caesalpinia bonducella growing in Dar es Salaam.     

Evaluation of cytotoxic, genotoxic and CYP450 enzymatic competition effects of Tanzanian plant extracts traditionally used for treatment of fungal infections

HIV-infected patients in sub-Saharan countries highly depend on traditional medicines for the treatment of opportunistic oral infections as candidiasis. Previous investigations on antifungal activity of medicinal plant extracts utilized by traditional healers in Tanzania have revealed 12 extracts with potent antifungal activity. Although the plants may be good candidates for new treatment opportunities, they can be toxic or genotoxic and could cause pharmacokinetic interactions when used concomitantly with antiretroviral agents. Therefore, we investigated the cytotoxicity, genotoxicity and cytochrome P450 interaction potential of these medicinal plants. Cytotoxicity was tested by Hoechst 33342, Alamar Blue, calcein-AM, glutathione depletion and O(2)-consumption assays and genotoxicity by a Vitotox assay. Competition of the 12 extracts on substrate metabolism by CYP3A4, 2C9, 2C19 and 2D6 was tested with high-throughput CYP inhibition screening. Pregnane X receptor (PXR) activation was tested using Chinese hamster ovary cell lines expressing human PXR. Herbal extracts inducing high human PXR activation were tested for enhanced CYP3A4 mRNA levels with quantitative polymerase chain reaction. Genotoxicity was found for Jatropha multifida, Sterculia africana and Spirostachys africana. All plant extracts showed high cytotoxic effects in almost all tests. Potent competition with CYP3A4, 2D6, 2C9 and 2C19 was found for 75% of the herbal extracts. Spirostachys africana did not affect CYP2D6 and for S. africana and Turraea holstii no effect on CYP2D6 and CYP3A4 (DBF) was found. Nine plant extracts showed significant activation of human PXR, but only Agaura salicifolia, Turraea holstii and S. africana significantly induced CYP3A4 mRNA levels. These results indicate the possibility of potential medicinal plant-antiretroviral interactions.     

Identification of factor VIII gene mutations in patients with severe haemophilia A in Venezuela: identification of seven novel mutations

Summary. Haemophilia A is caused by mutations in the gene encoding coagulation factor VIII (FVIII). In severe Haemophilia A (sHA), two inversions are responsible for approximately 50% of the genetic alterations (intron 22 and intron 1 inversions). The other mutations are extremely diverse and each affected family generally has its own mutation. Our aim was to detect the genetic alterations present in the FVIII gene (F8) in 54 unrelated male patients with sHA in Venezuela. We initially detected the presence of the intron 22 inversion by performing inverse PCR, and the negative patients for this inversion were analysed for the intron 1 inversion by PCR. Patients negative for both inversions were analysed using Conformation Sensitive Gel Electrophoresis for mutations in all exons, promoter region and 3′‐UTR. sHA causative mutations were identified in 49 patients. Intron‐22 and ‐1 inversions were detected in 41% and 0% of patients respectively. Besides these two mutations, 25 different mutations were identified, including nine nonsense, four small deletions, two small insertions, four missense, three splicing mutations and three large deletions. Seven novel mutations were identified, including two nonsense mutations, two small deletions, one small insertion, one missense mutation and one splicing mutation. Thirty one percent of the patients with identified mutations developed inhibitors against exogenous FVIII. This is the first report of F8 mutations in patients with sHA in Venezuela; the data from this study suggests that the spectrum of gene defects found in these patients is as heterogeneous as reported previously for other populations.     

Imaging characteristics of extrapulmonary tuberculosis lesions on dual time point imaging (DTPI) of FDG PET/CT

Introduction: This study aimed to evaluate the diagnostic value of dual time point imaging (DTPI) of 18F‐fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) for detecting the infective lesions in patients with extrapulmonary tuberculosis (EPTB). Methods: Eleven patients were consecutively recruited and evaluated. After the intravenous injection of 369 ± 153 MBq of FDG, all patients underwent FDG PET/CT imaging at two different time points: early scan at 57 ± 23 min and delayed scan at 136 ± 42 min. The maximum standardized uptake values (SUVmax) were recorded for both time points (early scan: SUVmax1 and delayed scan: SUVmax2). Results: In total, 30 lesions were detected. The SUVmax2 in 22 of the lesions in confirmed EPTB patients were significantly higher than the SUVmax1 (7.9 ± 3.2 vs. 6.8 ± 2.5; P = 0.001). The SUVmax for another eight non‐EPTB lesions also showed a significant increasing pattern of change (6.2 ± 2.6 vs. 6.5 ± 2.8; P = 0.044). However, there was insignificant difference between the mean percentage difference of SUVmax (%ΔSUVmax) of EPTB and non‐EPTB lesions (P = 0.06). Conclusion: Our study demonstrates that early whole body PET/CT imaging may be sufficient for the detection of the EPTB lesions and DTPI of PET/CT may also not be a useful technique in differentiating between EPTB and non‐EPTB lesions. However, our findings are based on a limited number of patients, and therefore, further investigations in larger series of patients are warranted.     

Lymphomas in sub‐Saharan Africa – what can we learn and how can we help in improving diagnosis,managing patients and fostering translational research?

Approximately 30 000 cases of non‐Hodgkin lymphoma (NHL) occur in the equatorial belt of Africa each year. Apart from the fact that Burkitt lymphoma (BL) is very common among children and adolescents in Africa and that an epidemic of human immunodeficiency virus (HIV) infection is currently ongoing in this part of the world, very little is known about lymphomas in Africa. This review provides information regarding the current infrastructure for diagnostics in sub‐Saharan Africa. The results on the diagnostic accuracy and on the distribution of different lymphoma subsets in sub‐Saharan Africa were based on a review undertaken by a team of lymphoma experts on 159 fine needle aspirate samples and 467 histological samples during their visit to selected sub‐Saharan African centres is presented. Among children (<18 years of age), BL accounted for 82% of all NHL, and among adults, diffuse large B‐cell lymphoma accounted for 55% of all NHLs. Among adults, various lymphomas other than BL, including T‐cell lymphomas, were encountered. The review also discusses the current strategies of the International Network of Cancer Treatment and Research on improving the diagnostic standards and management of lymphoma patients and in acquiring reliable clinical and pathology data in sub‐Saharan Africa for fostering high‐quality translational research.