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Biomedical subjects

I Bates

Publications and source records attributed to I Bates.

At least 19 recordsLinked to original sources
PubMed2000

Antimalarial bioavailability and disposition of artesunate in acute falciparum malaria.

The pharmacokinetic properties of oral and intravenous artesunate (2 mg/kg of body weight) were studied in 19 adult patients with acute uncomplicated Plasmodium falciparum malaria by using a randomized crossover design. A sensitive bioassay was used to measure the antimalarial activity in plasma which results from artesunate and its principal metabolite, dihydroartemisinin. The oral study was repeated with 15 patients during convalescence. The mean absolute oral bioavailability of the antimalarial agent in patients with acute malaria was 61% (95% confidence interval [CI], 52 to 70%). The absorption and elimination of oral artesunate were rapid, with a mean elimination half-life of antimalarial activity of 43 min (95% CI, 33 to 53 min). Following oral administration to patients with acute falciparum malaria, peak antimalarial activity in plasma and the area under the plasma concentration-time curve were approximately double those during convalescence and the apparent volume of distribution and clearance were approximately half those during convalescence (P < or = 0.005). Acute malaria is associated with a significant reduction in the clearance of artesunate-associated antimalarial activity.

Administration, Oral↗
PubMed1999

VH gene sequences from a novel tropical splenic lymphoma reveal a naive B cell as the cell of origin.

The prevalence of malaria and other infections in tropical Africa provides a setting for the emergence of B-cell tumours distinct from that in Western countries. Attempts to draw comparisons with Western lymphomas have led to difficulties, with so-called African chronic lymphocytic leukaemia (CLL) having a different pattern of incidence from Western CLL. Splenomegaly is common in African CLL, and this has posed diagnostic problems in differentiating the tumour from malaria-associated hyper-reactive malarial splenomegaly (HMS). One feature of the splenomegalic form of African CLL is that the tumour cells often possess short but fine cytoplasmic projections reminiscent of those observed in Western splenic lymphoma with villous lymphocytes (SLVL). Analysis of Ig VH genes both facilitates discrimination between clonal B-cell tumours and HMS, and reveals the differentiation status of the cell of origin. This study indicated that VH genes of nine cases of clonal splenic B-cell tumours with villous lymphocytes from Ghana were relatively unmutated, consistent with an origin from a naive B cell. These features differ from SLVL which arises from a post-follicular antigen-selected B cell. One possibility is that these splenic B-cell tumours derive from a splenic T-independent B cell, with malaria infection as a potential influence.

Adult↗
PubMed1998

Maternal viral load, CD4 cell count and vertical transmission of HIV-1.

HIV load and CD4 cell numbers were measured among 95 HIV infected women during pregnancy in order to determine their value as prognostic markers for transmission of virus from mother to infant. Among the 94 live births, 13 children were infected with HIV, 69 were uninfected and 12 were of unknown infection status. HIV RNA levels, as measured by nucleic acid sequence based amplification, were significantly higher (P < 0.001) in women who transmitted virus than among those who did not transmit and maternal viral load was a stronger predictor of transmission than CD4 cell number. The predicted rate of transmission relative to maternal HIV RNA was 2% at 1,000 copies, 11% at 10,000 copies and 40% at 100,000 copies/ml. Little variation in viral load occurred during pregnancy and there was an association between viral load and prematurity, the mean gestation at delivery decreasing by 1.3 weeks for every 10-fold increase in maternal HIV RNA (P = 0.007). This study demonstrates that a high level of maternal HIV RNA is a risk factor for transmission of virus to the infant and maternal viral load is of more value as a prognostic marker for transmission risk than CD4 cell number. High viral load is also associated with premature delivery. Maternal viral load is therefore a useful marker on which to base management decisions during pregnancy.

CD4 Lymphocyte Count↗
PubMed1998

Splenic lymphoma with villous lymphocytes should be included in the differential diagnosis of massive splenomegaly.

AIM: To distinguish between patients with reactive lymphocytosis and those with malignant lymphoid proliferations, with particular reference to hyper-reactive malarial splenomegaly and splenic lymphoma with villous lymphocytes. PATIENTS: Forty-four patients, residents of the Ashanti region of Ghana that is hyperendemic for Plasmodium falciparum malaria, were studied. All patients had splenomegaly greater than 10 cm. They were given proguanil 100 mg/day for a minimum of 6 months. Lymphocyte surface phenotypes were studied on the peripheral blood smears, immunoglobulin gene rearrangement by the Southern blot technique, serum IgM concentration using the Nor-Partigen-IgM kit, and serum paraprotein concentration by electrophoresis. RESULTS: Based on the response to proguanil, the patients were categorized into good respondents, partial respondents, and non respondents. Peripheral blood lymphocytes exceeded 30% in 19, and villous lymphocytes were less than 30% in 25 patients. CONCLUSION: Splenic lymphoma with villous lymphocytes may be difficult to differentiate from the African variant of chronic lymphocytic leukemia which is associated with splenomegaly and from hyperreactive malarial splenomegaly with lymphocytosis. In West Africa, a peripheral blood lymphocyte count greater than 10 x 109/L, with more than 30% of villous lymphocytes and failure of splenic regression with anti-malarial therapy suggest a diagnosis of splenic lymphoma with villous lymphocytes.

Adolescent↗
PubMed1997

Chronic malaria and splenic lymphoma: clues to understanding lymphoma evolution.

In west Africa, splenic lymphoma with villous lymphocytes and hyper-reactive malarial splenomegaly have many clinical and immunological features in common suggesting an aetiopathological link. We hypothesize that in hyper-reactive malarial splenomegaly the dysregulated immune response to repeated malaria infections results in a stimulated, proliferating pool of B cells in which perturbation of cell growth and apoptosis by environmental and other factors promotes the development of SLVL. In Africa these factors are likely to include infectious agents several of which have already been associated with B-cell non-Hodgkin's lymphomas.

Chronic Disease↗
PubMed1997

How to hone haematology skills.

In Ghana a pilot programme for the continuing education of haematology laboratory technicians has produced marked improvements in skills and has led to the development of a five-year strategy for national in-service training. The factors responsible for the success of the programme are outlined below.

Curriculum↗
PubMed1996

Antimalarial drugs reduce cytoadherence and rosetting Plasmodium falciparum.

The in vivo and in vitro effects of antimalarials on cytoadherence and rosette formation were studied in 17 patients with severe and 46 with uncomplicated falciparum malaria. Cytoadherence was increased in severe malaria (P<.001). Artesunate and artemether were more potent than quinine in inhibiting both adherence properties. Artesunate was the most rapidly acting drug tested, producing >50% inhibition of both cytoadherence and rosetting in vivo and in vitro within 2 hr of drug exposure. Exposure to quinine for > or = to 4 h in vivo reduced rosetting by >50%, but not cytoadherence. Quinine did not reduce cytoadherence or rosetting significantly in vitro with exposure times of < or = to 8 h. These results suggest that artemisinin derivatives are more effective than quinine in preventing pathologic processes in parasitized erythrocytes that contribute to microvascular obstruction in severe malaria.

Adolescent↗
PubMed1995

[the early diagnosis of the vertical transmission of the human immunodeficiency virus type 1. The evaluation of diagnostic tests].

BACKGROUND: The early diagnosis of vertically transmitted human immunodeficiency virus infection cannot be based on the presence of specific serum antibodies since those of the maternal IgG class pass the placenta and may be detected in children for up to 18 months. Based on this fact, the aim of this study was to evaluate other techniques for early diagnosis of the infection applicable from birth in 306 children of infected mothers. METHODS: The production of in vitro antibodies, virus culture and polymerase chain reaction (PCR) were used. The sensitivity of the techniques was estimated in the 40 children diagnosed with human immunodeficiency virus infection and specificity was determined in the 266 uninfected children. RESULTS: The sensitivity for the production of in vitro antibodies was 62.0% at 3 months and 94.7% at 6 months; 90.4% and 88.2%, respectively, for the viral culture and 92.3% and 94.1%, respectively, for the PCR. The specificity of all the cases was higher than 89.4% although varied in relation to age. CONCLUSIONS: The combination of several diagnostic techniques provides better performance for the early diagnosis of vertical transmission of the human immunodeficiency virus. Given that viral culture takes longer to provide results and is more expensive, it is less recommendable for routine use, although the form of viral replication may be useful to establish the prognosis.

Aging↗
PubMed1995

The efficacy of heparin in maintaining peripheral infusions in neonates.

UNLABELLED: The study set out to determine the survival times of peripheral total parenteral nutrition (TPN) infusion sites in neonates using a prospective, single blind, randomised trial design. The effects of various concentrations of co-administered heparin was measured using survival analysis, and of other continuous variables using multivariate analysis, against a non-heparinized control group. The study was conducted in special care baby unit located within a specialist maternity hospital in London, United Kingdom. Heparin at 0.1, 0.25, 0.5 and 1 IU/ml was added to TPN infusions delivered through peripheral veins and the survival times of the infusions determined. For infusion sites receiving heparinized fluids, the relative risk of failure decreased and the median survival time increased as the heparin concentration increased, with a maximal effect at a heparin concentration of 0.5 IU/ml (P < 0.001). Multivariate analysis using the Cox proportional hazard model confirmed the efficacy of heparin and highlighted a history of infusion therapy and the co-administration of gentamicin (from a range of drugs analysed) as being risk factors associated with infusion site failure. CONCLUSION: Intravenous infusion survival time can be prolonged using heparin additive at an optimal concentration of 0.5 IU/ml. This should also be of additional interest to paediatricians as heparin is an ubiquitous drug on neonatal units and its clinical use needs to be rationalised.

Blood Coagulation Tests↗
PubMed1995

Prognostic value of immunological data, in vitro antibody production, and virus culture in vertical infection with HIV-1.

The prognostic value of immunological indices, in vitro antibody production, and virus culture pattern at 3 months of age was estimated in 35 infants infected by HIV-1 from a cohort of 298 babies born to HIV-1 seropositive mothers and followed up from birth. At 1 year old, 15 of these infants were classified as stage P-1 (according to the Centers for Disease Control classification) seven were P-2A, and seven had AIDS. Significantly higher CD8 percentages, lower percentages and absolute value of CD4, and lower CD4/CD8 ratios at 3 months were observed in infants with severe symptoms at 1 year of age when compared with those who were asymptomatic at this age. Seventy seven per cent of infants with a 'rapid' virus culture when 3 months old had developed AIDS or had died by 1 year of age and only 8% of those with 'slow' virus culture had AIDS when 1 year old. Moreover, 100% of those who were asymptomatic at 1 year had a slow virus culture at 3 months. Significant statistical association was found between the virus replication pattern at 3 months and the clinical stage at 1 year of age.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Splenic lymphoma with villous lymphocytes in tropical West Africa.

Splenic lymphoma with villous lymphocytes (SLVL) is a monoclonal B-lymphoproliferative disorder characterised by splenomegaly and distinctive villous lymphocytes in the peripheral blood. It has not previously been reported from Africa, but we describe ten Ghanaian patients with SLVL seen at one hospital during a 4-year period. The clinical presentation is similar in Africa and in temperate regions, though the lymphocyte count is higher in African patients and the disorder predominantly affects middle-aged women rather than elderly men. It is likely that SLVL has previously been classified as splenic chronic lymphocytic leukaemia or hyper-reactive malarial splenomegaly.

Adult↗
PubMed1991

Use of immunoglobulin gene rearrangements to show clonal lymphoproliferation in hyper-reactive malarial splenomegaly.

In Africa, hyper-reactive malarial splenomegaly (HMS), which is also known as tropical splenomegaly syndrome, can be associated with a prominent lymphocytosis in blood and bone marrow that is difficult to distinguish clinically from chronic lymphocytic leukaemia (CLL). The observation that some patients with HMS become resistant to treatment with anti-malarial drugs has led to the suggestion that HMS may evolve into a malignant lymphoproliferative disorder. To test this hypothesis, 22 Ghanaian patients with HMS and/or lymphocytosis were categorised by degree of response to proguanil according to standard clinical criteria, and DNA was extracted from peripheral blood cells and screened for rearrangements of the Jh region of the immunoglobulin gene with a DNA probe. Clonal rearrangements of the Jh region were found in all 3 patients with no response, in none of 13 patients with sustained response, and in 2 of 6 patients with moderate response or relapse on proguanil therapy. The detection of such rearrangements, and hence clonal lymphoproliferation in individuals with clinical features intermediate between HMS and CLL, supports the hypothesis that HMS may evolve into a malignant lymphoproliferative disorder.

Adolescent↗
PubMed1991

Extracting, storing, and transporting whole blood DNA under tropical conditions.

A simple and robust technique for the extraction of DNA under tropical field conditions is described. It requires minimal equipment and is based on lysing cells in whole blood and precipitating the nuclei containing the DNA by centrifugation. The DNA solution can be stored in guanidinium buffer for many months without being refrigerated. Further purification of the DNA can then be carried out in a laboratory with facilities for ultracentrifugation by banding the DNA through cesium chloride. This method yields DNA of sufficient quality and purity for Southern blotting and probing and alleviates the need to transport whole blood between different countries and laboratories.

DNA↗
PubMed1991

Hyperreactive malarial splenomegaly in pregnancy.

Hyperreactive malarial splenomegaly (HMS) is common in many tropical areas and particularly affects women of reproductive age. It is associated with anaemia which can be debilitating in patients already compromised by anaemia due to poor nutrition and pregnancy. The course of the disorder in pregnancy is commonly punctuated by episodes of haemolytic anaemia which can be life-threatening to the mother and cause increased fetal morbidity and loss. Management of the chronic state consists of lifelong anti-malarial therapy supplemented by haematinics. Blood transfusions may be required to treat episodes of severe haemolysis.

Anemia↗