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Biomedical subjects

D R Brewster

Publications and source records attributed to D R Brewster.

At least 19 recordsLinked to original sources
PubMed1997

Case management of kwashiorkor: an intervention project at seven nutrition rehabilitation centres in Malawi.

OBJECTIVES: (1) To improve case management of kwashiorkor at seven Nutritional Rehabilitation Centres (NRCs) through 2-4 weekly paediatric supervisory visits. (2) To evaluate the impact of the use of routine tube-feeding and a micronutrient supplement (Nutriset). DESIGN: An intervention project with descriptive clinical data in which Nutriset was introduced halfway through the project, and routine tube-feeding at one NRC was compared to no tube-feeding at a similar one. SETTING: NRCs located at two central hospitals, two district hospitals and three rural clinics in southern Malawi. SUBJECTS: 1625 consecutive kwashiorkor admissions from January-December 1995. RESULTS: The overall case-fatality rate was 24.2% (393/1625), varying by facility level (central 30.5%, district 25.8% and rural 7.5%), reflecting different severity of cases. From ELISA testing and a clinical protocol, we estimate that 21.7% (353/1625) of these kwashiorkor cases were HIV-infected, including 121 breastfed children. Routine tube-feeding was associated with better weight gain (8.24 g/kg/d) than no tube-feeding (4.51 g/kg/d) at central NRCs, but with no reduction in mortality (31.4% vs 30.3%). The introduction of Nutriset was associated with improved weight gain (6.06 vs 4.66 g/kg/d) and a lower mortality (20.8 vs 25.8%), but was confounded by seasonal factors. CONCLUSIONS: From a clinical perspective, HIV infection has transformed kwashiorkor in this part of Africa. Routine tube-feeding was associated with improved body weight gain in the treatment of kwashiorkor. The benefit of paediatric supervision was limited by the infrequency of visits, by constraints of health worker motivation, by a lack of resources and by the severity of disease. Efforts need to focus-not just on case management protocols-but on how to actually improve clinical practice in this setting.

Case Management↗
PubMed1997

Protein metabolism in children with edematous malnutrition and acute lower respiratory infection.

This study tested the hypothesis that wholebody protein kinetics remain low in children with edematous malnutrition and acute infection. Thirteen children with edematous malnutrition and acute infection (subjects) were compared with 14 uninfected children with edematous malnutrition early in recovery (control children). Protein kinetics were determined by using a primed, constant intravenous infusion of [13C]leucine and [15N2]urea in the postabsorptive state. Calculations of rates of whole-body protein synthesis and breakdown were based on the rate of leucine appearance; the rate of leucine oxidation was estimated from the rate of urea appearance. Protein synthesis and breakdown rates were lower in subjects than in control children (97 +/- 30 compared with 153 +/- 67, P < 0.01, and 103 +/- 30 compared with 160 +/- 67 mumol leucine.kg-1.h-1, P < 0.01). No difference was found between the two groups in the rate of urea appearance, but this analysis only had a statistical power of 54%. The absence of the expected increase in the rate of protein turnover during acute infection in edematous malnutrition implies that acute phase proteins are made with a corresponding depletion of muscle, hepatic, and other body proteins such as albumin, and that there may also be a blunting of the acute phase response.

Acute Disease↗
PubMed1997

Whole-body protein kinetics in children with kwashiorkor and infection: a comparison of egg white and milk as dietary sources of protein.

This study tested the hypothesis that during treatment of kwashiorkor (including marasmic kwashiorkor) with infection there is a lower rate of amino acid oxidation when the dietary intake of amino acids resembles the amino acid composition of acute phase proteins (APPs). Twenty-two children in Blantyre, Malawi, with kwashiorkor and acute infection were fed an isoenergetic, isonitrogenous diet with either egg white or milk as a protein source. The whole-body amino acid oxidation rate was measured after 24 h by determining the plasma urea rate of appearance, and whole-body protein breakdown and synthesis rates were determined from the plasma leucine rate of appearance. Plasma concentrations of C-reactive protein, alpha1-antitrypsin, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) were determined on admission and at 24 and 48 h. The 11 children who received milk had a lower rate of amino acid oxidation than the children who received egg white (x +/- SD: 137 +/- 65 compared with 195 +/- 66 micromol urea x kg body wt(-1) x h(-1), P < 0.05). No significant differences were found between the two groups in the rate of whole-body protein breakdown or protein synthesis. The TNF-alpha concentration correlated inversely with whole-body protein breakdown and synthesis rates, and the IL-6 concentration correlated directly with C-reactive protein. We conclude that by making the amino acid composition of the diet resemble that of APPs in the treatment of acute kwashiorkor, the rate of amino acid oxidation can be decreased.

C-Reactive Protein↗
PubMed1997

Potassium supplementation in kwashiorkor.

BACKGROUND: Kwashiorkor is an edimatous form of severe malnutrition and is the predominant form of childhood malnutrition in Malawi. Potassium depletion is common and contributes to the high mortality. The aim of this study was to determine if high potassium supplementation improves the outcome of kwashiorkor treatment. METHODS: We performed a randomised, double-blind, placebo-controlled, clinical trial of high potassium supplementation in 99 children with kwashiorkor. Controls (n = 51) received a standard potassium intake of 4.7 mmol/kg/day. The intervention group (n = 48) received 7.7 mmol/kg/day. All cases (intervention and control groups) were treated in the hospital-based Nutrition Rehabilitation Center and received a standard treatment regime of mild feeds, mineral and vitamin supplements, and antibiotics. RESULTS: There was no significant difference in length of hospitalization, or time for resolution of oedema between groups. The case-fatality rate was reduced by 33% in the high potassium intervention group (13/48) compared to controls (21/51). There was a significant reduction in late deaths (13 in controls vs 3 in intervention group; odds ratio 5.3, 95% confidence interval 1.2-31.0) but no difference in early deaths (0-5 days). The intervention group also had significantly fewer presumed septic episodes (3 vs 18, odds ratio 8.9, confidence interval 2.2-50.9), respiratory symptoms, and new skin ulcerations than controls. CONCLUSIONS: The high potassium supplementation reduced mortality and significant morbidity in kwashiorkor. This may be due to improved myocardial and immune function from earlier repletion of intracellular potassium. We recommend that the standard potassium supplement for the initial phase of treatment of kwashiorkor be increased from 4 to 8 mmol/kg/day.

Administration, Oral↗
PubMed1997

Intestinal permeability in kwashiorkor.

UNLABELLED: Intestinal permeability can be assessed non-invasively using the lactulose-rhamnose (L-R) test, which is a reliable measure of small intestinal integrity. AIMS: To determine risk factors for abnormal intestinal permeability in kwashiorkor, and to measure changes in L-R ratios with inpatient rehabilitation. DESIGN: A case-control study of 149 kwashiorkor cases and 45 hospital controls. The L-R test was adapted to study kwashiorkor in Malawi, with testing at weekly intervals during nutritional rehabilitation. Urine sugars were measured by thin layer chromatography in London. RESULTS: The initial geometric mean L-R ratios (x100) (with 95% confidence interval) in kwashiorkor were 17.3 (15.0 to 19.8) compared with 7.0 (5.6 to 8.7) for controls. Normal ratios are < 5, so the high ratios in controls indicate tropical enteropathy syndrome. Abnormal permeability in kwashiorkor was associated with death, oliguria, sepsis, diarrhoea, wasting and young age. Diarrhoea and death were associated with both decreased L-rhamnose absorption (diminished absorptive surface area) and increased lactulose permeation (impaired barrier function) whereas nutritional wasting affected only L-rhamnose absorption. Despite, clinical recovery, mean L-R ratios improved little on treatment, with mean weekly ratios of 16.3 (14.0 to 19.0), 13.3 (11.1 to 15.9) and 14.4 (11.0 to 18.8). CONCLUSION: Abnormal intestinal permeability in kwashiorkor correlates with disease severity, and improves only slowly with nutritional rehabilitation.

Case-Control Studies↗
PubMed1997

Comparison of milk and maize based diets in kwashiorkor.

UNLABELLED: The dual sugar test of intestinal permeability is a reliable non-invasive way of assessing the response of the small intestinal mucosa to nutritional rehabilitation. AIM: To compare a local mix of maize-soya-egg to the standard milk diet in the treatment of kwashiorkor. DESIGN: The diets were alternated three monthly in the sequence milk-maize-milk. There were a total of 533 kwashiorkor admissions of at least five days during the study who received either milk or maize. Intestinal permeability was assessed at weekly intervals by the lactulose-rhamnose test in 100 kwashiorkor cases, including 55 on milk and 45 on the maize diet. RESULTS: Permeability ratios (95% confidence interval) on the milk diet improved by a mean of 6.4 (1.7 to 11.1) compared with -6.8 (-16.8 to 5.0) in the maize group. The improved permeability on milk occurred despite more diarrhoea, which constituted 34.8% of hospital days (29.8 to 39.8) compared with 24.3% (17.8 to 30.8) in the maize group. Case fatality rates for all 533 kwashiorkor admissions were 13.6% v 20.9%, respectively, giving a relative risk of death in the maize group of 1.54 (1.04 to 2.28). The maize group also had more clinical sepsis (60% v 31%) and less weight gain (2.9 v 4.4 g/kg/day) than the milk group. IMPLICATIONS: Milk is superior to a local maize based diet in the treatment of kwashiorkor in terms of mortality, weight gain, clinical sepsis, and improvement in intestinal permeability.

Animals↗
PubMed1996

Chloramphenicol-resistant bacterial meningitis in Malawi.

Three recent cases of chloramphenicol-resistant pyogenic meningitis are reported from Malawi. The implications of the emergence of antibiotic-resistant strains of Streptococcus pneumoniae and Haemophilus influenzae type b causing childhood meningitis are discussed.

Child↗
PubMed1993

Seasonal variation of paediatric diseases in The Gambia, west Africa.

In a 3-year prospective study of 9584 consecutive paediatric admissions to the Royal Victoria Hospital in Banjul, The Gambia, we examined the impact of seasonal variations in childhood diseases. The four principal diseases (falciparum malaria, pneumonia, gastro-enteritis and malnutrition) all peaked in September to October following the rainy season. The mortality rate was also higher in the rainy season than in the dry season. Of the 1525 children with cerebral malaria, 83% were admitted during the extended rainy season from July to December. With the emergence of chloroquine-resistant malaria over the 3 years, there was a 27% annual increase in severe anaemia owing to malaria. The median age of malarial anaemia (23 months) was significantly younger than that of cerebral malaria (42 months). Malnutrition peaked immediately following the annual rainy season epidemics of bacterial gastro-enteritis but was not associated with the cool dry season rotavirus outbreaks. Rainy season diarrhoea was also associated with more persistent diarrhoea, an older mean age and a higher mortality. Meningitis was caused by either pneumococcus or Haemophilus influenzae in 64% of cases, of whom 19% were 0-2 months of age. Causes of death in hospital showed good agreement with Gambian community studies. We conclude that analysis of hospital data in a developing country can give accurate information on childhood morbidity and mortality patterns which can be used to set priorities for health care interventions. Seasonal variation is a cardinal feature of paediatric diseases in this part of Africa, and accentuates the vulnerability of children in poor families.

Child↗
PubMed1993

Treatment of acute bronchiolitis with Chinese herbs.

In a randomised single blind trial the Chinese herbs Shuang Huang Lian were evaluated for the treatment of acute bronchiolitis. Children with acute bronchiolitis and serological evidence of recent respiratory syncytial virus infection were studied in a tertiary hospital in Harbin, China. The 96 children were randomised into three treatment groups: herbs, herbs with antibiotics, and antibiotics alone. The herbs were prepared by the medical school pharmacy and administered daily by intravenous infusion for seven days. The main outcomes, assessed blindly, were symptomatic improvement in cough, fever, wheezing, chest signs, and duration of stay in hospital. The mean duration of symptoms from the start of treatment was 6.2 (confidence interval 5.6 to 6.9) days in the two groups treated with herbs compared with 8.6 (confidence interval 7.5 to 9.8) days in the group treated with antibiotics alone. The mean reductions in duration of clinical manifestations for treatment with antibiotics alone compared with herbs were: from 3.1 to 1.5 days for fever, 9.1 to 6.1 days for cough, 6.5 to 4.1 days for wheezing, and 7.2 to 4.9 days for chest crackles. No adverse effect of Shuang Huang Lian herbal treatment was detected. In conclusion, this study confirms Chinese experience with Shuang Huang Lian that it is safe and effective, and warrants further study.

Acute Disease↗
PubMed1993

Evaluation of the ARI program: a health facility survey in Simbu, Papua, New Guinea.

The purpose of this health facility survey was to evaluate how the ARI (Acute Respiratory Infection) Program actually works in an everyday, non-research setting. We surveyed 33 clinics and aid posts, including 223 children with ARI and 104 health workers. In this primary health care setting, health workers diagnosed 37% of ARI cases as pneumonia, compared to 69% in the same children assessed independently by trained ARI surveyors using Papua New Guinea case management, which defines fast breathing as > or = 40 per minute for children 1 month to 5 years of age. Agreement between health workers and surveyors was reasonably good (kappa > or = 0.6) for the history of symptoms, but was poor (kappa < 0.3) for diagnoses, treatments and signs such as respiratory rate (RR) and chest indrawing. Health workers counted the RR in only 14% of cases in the survey. In essence, we found that health workers in Simbu are not practising ARI case management. We conclude that case management guidelines which define fast breathing as a rate of > or = 40 per minute classify too many obviously well children as pneumonia. Furthermore, we encountered difficulties in measuring RR accurately, and documented marked inter-observer variation in this setting. Consequently, we are concerned about the ARI Program's excessive reliance on RR and rigid protocols at the expense of clinical sense. Case management guidelines developed for aid post orderlies or village health workers may need to be modified, or used differently by experienced nurses at health centres, who recognize sick children better than by following a standardized protocol. Despite better overall ARI knowledge and practice by nurses, we could demonstrate an impact of the ARI Training Program only on community health workers (CHWs). In order to improve ARI clinical practice, we recommend that the ARI Program in PNG initiates regular on-site clinical supervision of nurses and CHWs at health centres.

Acute Disease↗
PubMed1993

Anti-TNF therapy inhibits fever in cerebral malaria.

The clinical effects of a murine monoclonal antibody (CB0006) directed against tumour necrosis factor were investigated in an open study of 41 Gambian children receiving otherwise conventional therapy for cerebral malaria. Ten children received a single i.v. dose of CB0006 at 0.1 mg/kg, 10 received 1 mg/kg, 10 received 5 mg/kg, and 11 were randomly selected as controls. CB0006 rapidly formed complexes with tumour necrosis factor, which were cleared from the circulation over several days. This was associated with a dose-dependent increase in total plasma tumour necrosis factor levels and a dose-dependent reduction of fever, implying that CB0006 inhibits tumour necrosis factor by retaining it in the circulation and reducing its availability to tissue receptors. Parasite clearance rates were not impaired. The fatality rate (29% overall) was similar in CB0006-treated patients and controls, but evaluation of possible effects on mortality requires a much larger blinded study. These data show that tumour necrosis factor is involved in the pathogenesis of malaria fever, and are the first direct evidence that inhibition of a specific endogenous pyrogen can attenuate fever in man.

Animals↗
PubMed1992

Extensive genetic diversity in the HLA class II region of Africans, with a focally predominant allele, DRB1*1304.

Molecular HLA class II typing of greater than 1700 individuals from The Gambia in West Africa and Malawi in South-Central Africa revealed a striking diversity of HLA DRB-DQB haplotypes as defined by restriction fragment length polymorphism (RFLP); this diversity is twice as extensive as that found in northern Europeans. Despite this diversity, sequence and PCR/oligonucleotide analysis showed that the recently described variant DRB1*1304 is the commonest DRB1 allele in The Gambia. The sequence, geographical distribution, and RFLP association of this allele, together with homozygosity test results, suggest that DRB1*1304 may have arisen from DRB1*1102 and have reached its remarkably high frequency as a result of recent directional selection. The prevalence of this unusual allele has implications for trials of subunit vaccines in this area. The extensive and distinctive HLA class II region polymorphism in sub-Saharan Africans is consistent with evidence from other genetic loci implying an African origin of modern Homo sapiens.

Alleles↗
PubMed1990

TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria.

Plasma levels of tumour necrosis factor (TNF) were significantly higher in 178 Gambian children with uncomplicated malaria due to Plasmodium falciparum than in 178 children with other illnesses. 110 children with cerebral malaria were studied shortly after admission to hospital; 28 subsequently died. Compared with the children with uncomplicated malaria, mean plasma TNF levels were twice as high in cerebral malaria survivors and ten times as high in the fatal cases. Although high TNF levels were associated with high parasitaemia and with hypoglycaemia, they predicted fatal outcome in cerebral malaria independently of parasitaemia and glucose concentrations. Concentrations of interleukin-1 alpha, but not interferon gamma, were also related to the severity of malaria. We conclude that increased TNF production is a normal host response to P falciparum infection, but that excessive levels of production may predispose to cerebral malaria and a fatal outcome.

Animals↗
PubMed1990

Neurological sequelae of cerebral malaria in children.

Out of 604 Gambian children admitted with falciparum malaria to one hospital between September and December, 1988, 308 had cerebral malaria and 203 were severely anaemic (haemoglobin less than 60 g/l). 14% of those with cerebral malaria died, as did 7.8% of those with severe anaemia. 32 (12%) of children surviving cerebral malaria had residual neurological deficit. 69 other children were admitted with clinical features strongly suggestive of cerebral malaria but with negative blood films; 16 of these died and 3 had residual neurological deficits. The commonest sequelae of cerebral malaria were hemiplegia (23 cases), cortical blindness (11), aphasia (9), and ataxia (6). Factors predisposing to sequelae included prolonged coma, protracted convulsions, severe anaemia, and a biphasic clinical course characterised by recovery of consciousness followed by recurrent convulsions and coma. At follow up 1-6 months later over half these children had made a full recovery, but a quarter were left with a major residual neurological deficit. Cerebral malaria in childhood may be an important cause of neurological handicap in the tropics.

Adolescent↗
PubMed1984

Substance P recognition by a subset of human T lymphocytes.

The interaction of substance P with human blood T-lymphocytes, which stimulates T-lymphocyte proliferation, was quantified by both flow cytometric and direct binding assays. Fluorescence-detection flow cytometry recorded the binding of dichlorotriazinylamino-fluorescein-labeled substance P to 21 +/- 10% (mean +/- SD, n = 6) and 35 +/- 8% (n = 2) of human blood T-lymphocytes before and after stimulation with 10 micrograms/ml of phytohemagglutinin, respectively. The suppressor-cytotoxic (leu 2a) and helper-inducer (leu 3a) subsets identified by phycoerythrin-labeled monoclonal antibodies contained substance P-reactive T-lymphocytes at respective mean frequencies of 10 and 18%. [3H]substance P bound rapidly and reversibly to a mean of 7035 +/- 2850 sites/T-lymphocyte, which exhibited a dissociation constant (KD) of 1.85 +/- 0.70 X 10(-7) M (mean +/- SD, n = 5). [D-Pro2,D-Phe7,D-Trp9]substance P inhibited the binding of dichlorotriazinylamino-fluorescein-labeled substance P and [3H]substance P to T-lymphocytes at concentrations that suppressed the proliferative response to substance P. Substance P, eledoisin, and substance K (alpha-neurokinin), which all share with substance P the carboxy-terminal substituent -Gly-Leu-Met-NH2, were more potent than substance P in inhibiting the binding of [3H]substance P to T-lymphocytes, suggesting the importance of this sequence in the interaction. Purified human blood B-lymphocytes, monocytes, polymorphonuclear leukocytes, and platelets, and cultured Hut 78 cutaneous lymphoma T-cells, Jurkat cells, Molt-4 lymphoblasts, and HL-60 and U-937 monocyte-like cells all showed only minimal specific binding of [3H]substance P. The recognition of substance P by T-lymphocytes provides one mechanism for selective modulation of immunity by sensory nerves.

Binding, Competitive↗
PubMed1984

Stereospecific receptors for substance P on cultured human IM-9 lymphoblasts.

The neuropeptide substance P (SP), which has been demonstrated to bind specifically to human blood T lymphocytes and to stimulate their uptake of [3H]thymidine and [3H]leucine, now is shown to bind stereospecifically to cultured human lymphoblasts of the IM-9 line. The specific binding of [3H]SP by IM-9 lymphoblasts increases linearly with the concentration of IM-9 lymphoblasts, achieves a plateau after approximately 15 to 20 min at 4 degrees C and 4 to 6 min at 37 degrees C, and is rapidly reversible at both 4 degrees C and 37 degrees C. The binding of [3H]SP at steady-state conditions demonstrates a dissociation constant (KD) of 0.65 +/- 0.19 nM (mean +/- SD, n = 5) and 22,641 +/- 6143 receptors per IM-9 lymphoblast. Maximal specific binding of [3H]SP to IM-9 lymphoblasts is observed at pH 7.4 and is dependent on the presence of Mg2+, but not Ca2+, in the medium. The peptide structural determinants of the inhibition of binding of [3H]SP to IM-9 lymphoblasts by substituent peptides and homologs of SP indicate that the receptors recognize predominantly the carboxy-terminal portion of SP. The characteristics of the interaction of SP with IM-9 lymphoblasts suggests a receptor-directed mechanism by which neuropeptides may modulate specifically the contributions of lymphocytes to immunity.

Binding, Competitive↗