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Biomedical subjects

M English

Publications and source records attributed to M English.

At least 19 recordsLinked to original sources
PubMed1999

Tuberculosis among homeless people in London: an effective model of screening and treatment.

SETTING: Hostels and day centres for homeless people in south London. OBJECTIVE: To develop an appropriate and effective method of screening for pulmonary tuberculosis (TB) among the homeless. DESIGN: Observational study evaluated for acceptability, yield of cases and completion of treatment. The screening included a symptom questionnaire, a Heaf test and a chest X-ray, developed and read on site. RESULTS: Ten clients (0.5%) were identified as having active pulmonary TB; seven of these were white men over the age of 50. The symptom questionnaire was seldom helpful. Nine of the cases were initially identified by chest X-ray, however only three of the 10 had a Heaf test performed. Eight of the 10 clients with active TB completed therapy; five additional clients were started on chemoprophylaxis. All of these had strongly positive Heaf reactions and normal chest X-rays. CONCLUSIONS: Chest X-ray screening is the most useful screening method and is effective if it is targeted. The use of incentives seems to increase the uptake of screening. Heaf testing is useful for the identification of those clients needing prophylactic treatment or BCG immunisation. Good compliance can be achieved provided clients are case managed appropriately.

Adult↗
PubMed1998

Acute changes in urine protein excretion may predict chronic ifosfamide nephrotoxicity: a preliminary observation.

PURPOSE: To evaluate proteinuria occurring early after ifosfamide therapy and to assess the use of changes in proteinuria in the prediction of severe chronic nephrotoxicity. METHODS: One-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to characterize urine protein excretion in 12 children with solid tumours before and after the first course of ifosfamide treatment, and in 24 healthy children. Chronic nephrotoxicity was evaluated at 6 months after ifosfamide treatment and graded as none, mild, moderate or severe. RESULTS: Urine from healthy children and from 10 of 12 patients before ifosfamide therapy showed a protein band with a molecular weight (95.4 kDa) corresponding to that of Tamm-Horsfall protein but no lower molecular weight proteins. After the first course of ifosfamide this 95.4-kDa protein was lost in six of ten patients with a concomitant appearance of a low molecular weight proteinuria (< 70 kDa) in eight. Tamm-Horsfall protein was lost in two of five patients who subsequently developed no or mild nephrotoxicity and in four of five patients who subsequently developed moderate or severe nephrotoxicity. CONCLUSIONS: Early subclinical changes in urine protein excretion after ifosfamide, manifested by a loss of Tamm-Horsfall protein excretion, may be predictive of subsequent chronic nephrotoxicity.

Adolescent↗
PubMed1998

Ventricular late potential analysis with musical and harmonic wavelets.

Harmonic and musical wavelets were introduced by DE Newland in 1994, and have their spectrum tightly defined, therefore greatly reducing spectral leakage that may disturb signal frequency analysis. We have explored the ability of these wavelets to perform detection and quantification of ventricular late potentials (VLP) through our multiresolution time-scale method of energy comparison between the ST and TP segments of the ECG. Since reduction of spectral leakage improves the method's reliability, Newland wavelets provided better results than Daubechies wavelets in our study cases. The only drawback is the comparatively reduced time resolution of Newland wavelets. This required us to concatenate a number of ST segments to form a longer data set that is more representative of the high-resolution ECG (HR-ECG) of a patient than one individual beat. This approach may also be considered for other applications in the HR-ECG field. The spectral properties of the Newland wavelets play a major role in the improvement in our results.

Calibration↗
PubMed1998

Hypoglycaemia on and after admission in Kenyan children with severe malaria.

We investigated the pathophysiology of hypoglycaemia in severe malaria in African children, especially the potential importance of glycerol as a substrate for gluconeogenesis, and whether substrate limitation contributes to hypoglycaemia in severe disease. Of 171 children with moderate or severe malaria, 16% were hypoglycaemic on admission, while at least 9% of children with severe malaria treated with quinine and a concurrent 4% dextrose infusion had a definite episode of hypoglycaemia after admission. Blood levels of gluconeogenic precursors are as high (alanine and lactate) or higher (glycerol) in those with either hypoglycaemia on or after admission as they are in children never having an episode of hypoglycaemia. Among children with severe malaria, however, those having a definite episode of hypoglycaemia at some stage are more acidotic and have greater evidence of renal impairment than those who are never hypoglycaemic (mean base excess -14.4 vs. -7.2, p < 0.001, mean creatinine 97 vs. 64, p < 0.001 and mean urea 8.1 vs. 5.8, p = 0.03, respectively). These data do not support a role for reduced gluconeogenic substrate supply in the pathogenesis of hypoglycaemia in severe childhood malaria, but do support the hypothesis that gluconeogenesis is impaired. Commonly-used bedside blood glucose monitoring devices may overestimate blood glucose measurements in the normal range, and paradoxically may also seriously overestimate the frequency of hypoglycaemia.

Chi-Square Distribution↗
PubMed1997

Two N-terminal self-association domains are required for the dominant negative transcriptional activity of WT1 Denys-Drash mutant proteins.

Patients with Denys-Drash syndrome (DDS) have been shown to be constitutionally heterozygous for mutations of the WT1 gene. Almost all DDS mutations inactivate or remove the DNA-binding zinc finger region of WT1 and the resulting mutant proteins appear to act in a dominant negative manner. This may occur via WT1 self-association, which has been shown to involve the first 180 amino acids. By creating a series of N-terminal deletions, we have further investigated WT1 self-association using a yeast di-hybrid system and an in vitro protein binding assay. Our results suggest that there are two distinct domains within the N-terminal region facilitating self-association, residing from amino acids 1-45 and 157-253. Co-transfection of WT1 with progressively shorter N-terminal constructs demonstrates that both of these sites are required for a dominant negative activity as assessed by activation of a reporter construct.

Base Sequence↗
PubMed1997

An intranet database for pacemaker patients.

A database system, incorporating smartcard technologies, was designed to hold the personal and pacing details of pacemaker patients, who attended a clinic at the Royal Sussex County Hospital (RSCH), Brighton, UK. Following an initial period of a 12 month clinical trial, with the database running on a standalone personal computer, the Pacemaker Patient Database has been redesigned and implemented as an intranet-based system. This paper describes the issues relating to the development of the new prototype system and identifies the design principles for intranet-based electronic health care (EHCR) record database systems.

Computer Communication Networks↗
PubMed1997

Acidosis in severe childhood malaria.

Data were prospectively collected on 306 Kenyan children, including blood gases in 258 (75%). Severe malaria caused a predominantly high-anion-gap metabolic acidosis in at least 43% of children. Children with coma and respiratory distress (CM + RD) had greater evidence of renal dysfunction, lower mean pH and higher mean plasma osmolality than those with respiratory distress (RD) or coma (CM) as isolated findings (mean urea 10.7 vs. 6.0 vs. 4.3 mmol/l; mean creatinine 97 vs. 74 vs. 58 mumol/l; mean osmolality 301 vs. 288 vs. 283 mosmol/l; and mean pH 7.16 vs. 7.29 vs. 7.39, respectively, p < 0.001 for each comparison of CM + RD vs. RD or CM). In addition, children with CM + RD had a higher mean blood lactate (6.7 vs. 3.3 mmol/l, p < 0.001), a lower mean haemoglobin (5.5 vs. 7.0 g/dl, p = 0.002) and a lower mean age (26.4 vs. 41.9 months, p < 0.001) than children with CM and accounted for 15/24 (63%) of all deaths. These and previous data implicate hypovolaemia and renal impairment in the pathogenesis of metabolic acidosis in severe childhood malaria. In children who are acidotic, anaemia is strongly associated with lactic acidaemia and may therefore contribute to its pathogenesis. These data also imply that coma in acidotic children (CM + RD) and those with an isolated encephalopathy (CM) may result from quite different pathophysiological mechanisms.

Acidosis↗
PubMed1997

Lactic acidosis and oxygen debt in African children with severe anaemia.

A syndrome of severe anaemia (Hb < or = 5 g/dl), particularly severe malarial anaemia (SMA), remains a major cause of childhood mortality in sub-Saharan Africa. We hypothesized that the lactic acidosis which identifies those at the greatest risk of death often represents an oxygen debt incurred as a result of inadequate tissue perfusion. To examine this hypothesis, we measured oxygen consumption (VO2) using a portable metabolic monitor. Blood lactate and acid-base status were also determined. Pre-transfusion data on 44 children (28 with mild symptoms, 7 with respiratory distress and 9 controls) demonstrated very close dependence of VO2 on body surface area (BSA, R2 = 0.86, p < 0.001). After correcting for BSA, no significant differences were observed in mean VO2 values of the three clinical groups, indicating that a critical reduction in oxygen delivery is not the sole explanation for the development of a lactic acidosis and severe symptoms. Nine children (including five of the original 44) were monitored during transfusion. In four of the five with SMA, severe symptoms and severe lactic acidosis, transfusion produced a marked, transient increase in VO2 (maximum 30-41%), with a marked fall in blood lactate and clinical improvement. These data suggest that some children with SMA and respiratory distress accumulate an oxygen debt when a relatively high oxygen demand outstrips supply, this debt being repaid when supply is increased during transfusion. However, in the remaining one of these five children, an increase in VO2 (maximum 20%), was accompanied by a rise in blood lactate and clinical deterioration, suggesting that more pathophysiologically complex mechanisms, which may predominate in some children.

Acidosis, Lactic↗
PubMed1997

Intracranial hypertension in Africans with cerebral malaria.

The causes of death and neurological sequelae in African children with cerebral malaria are obscure. Intracranial pressure (ICP) was monitored and cerebral perfusion pressure (CPP) calculated in 23 Kenyan children with cerebral malaria. Four children had severe intracranial hypertension (ICP > 40 mm Hg, CPP < 40 mm Hg): two died, one with an ICP of 158 mm Hg and signs of transtentorial herniation, the other one with an ICP of 42 mm Hg and cardiorespiratory arrest. The other two survived with severe neurological sequelae. Nine had intermediate intracranial hypertension (ICP > 20 mm Hg, CPP < 50 mm Hg) and 10 had mild intracranial hypertension (maximum ICP 10-20 mm Hg); all survived without severe sequelae. Mannitol controlled the ICP in children with intermediate intracranial hypertension, but it did not prevent the development of intractable intracranial hypertension in children with severe intracranial hypertension. Intracranial hypertension is a feature of Kenyan children with cerebral malaria and severe intracranial hypertension is associated with a poor outcome.

Child↗
PubMed1996

Chronic salicylate poisoning and severe malaria.

BACKGROUND Salicylates continue to be marketed and to be used in developing countries as over-the-counter (OTC) antipyretics in children, whereas in developed countries they are no longer used in children because of safety concerns. The presenting signs of salicylate poisoning, especially chronic (repeated administration of therapeutic or excessive doses for longer than 12 h), can include metabolic acidosis, hypoglycaemia, lethargy, and coma and fits. These signs are also common in severe malaria in African children. Admission of two probable cases of chronic salicylate poisoning prompted us to look for other cases among children presenting to our hospital in Kenya, apparently with severe malaria. METHODS All children admitted to Kilifi District Hospital between July and September, 1994, who had a positive blood film for Plasmodium falciparum, and one or more of coma, prostration, or respiratory distress were eligible. As well as routine tests for malaria and routine biochemistry, salicylate concentrations were measured. Management of children (aged 6 months to 10 years) in the community was assessed by a cross-sectional survey of 463 households and by interviews with mothers 2 days after they had bought OTC drugs for a child with fever. FINDINGS Data were available for 143 of 154 children with initial primary diagnoses of severe malaria. 129 (90 percent) had detectable (>l mg/dL) salicylate. Six of these had salicylate concentrations of 20 mg/dL or higher. All six had neurological impairment and metabolic acidosis and four were, or became, hypoglycaemic. OTC drugs were the first-line treatment in 188 (74 percent) of 254 fever episodes during the 2 weeks before the cross-sectional survey. Of 250 mothers who bought drugs for a febrile child, 236 (94 percent) bought a preparation containing salicylates and 50 (21 percent) gave a dose higher than the manufacturer's recommended maximum. INTERPRETATION These cases suggest that in some children salicylate poisoning may cause or contribute to the development of metabolic acidosis and hypoglycaemia, complications of severe malaria associated with high mortality.

Acidosis↗
PubMed1996

The effect of treatment with high dose melphalan, cisplatin or carboplatin on levels of glutathione in plasma, erythrocytes, mononuclear cells and urine.

Glutathione(GSH) has been implicated as an important factor in the detoxification of many electrophilic xenobiotics, including agents used in cytotoxic chemotherapy. Maintenance of high levels of GSH in normal tissues is believed to be important in the prevention of drug-induced toxicity. Previous studies have indicated that exposure of cells to some toxic electrophiles both in vitro and in vivo can cause a temporary decrease in intracellular levels of GSH. In this paper we report that in a series of 22 children and young adults treated with high dose melphalan (ten courses studied, all 200 mg/m2), cisplatin (eight courses, 80-104 mg/m2) or carboplatin (seven courses, 507-750 mg/m2) there was no significant alteration in the level of plasma, erythrocyte or urine GSH in the period immediately following drug administration. Fluctuations in the level of GSH in mononuclear cells were observed in some patients but did not follow any consistent pattern and were similar to those observed in a series of nine normal adult controls over the same time course. These results suggest that for melphalan, cisplatin and carboplatin, drug-GSH adduct formation is insufficient to cause a measurable decrease in intracellular GSH levels in normal peripheral haematopoietic cells during the course of treatment.

Adolescent↗
PubMed1996

Ifosfamide nephrotoxicity: limited influence of metabolism and mode of administration during repeated therapy in paediatrics.

This study investigated the relationship between both acute and chronic nephrotoxic effects of ifosfamide (IFO) and its metabolism. 15 paediatric patients (4 girls) were investigated. Each received 6-9 g/m2 IFO over 15 days, repeated every 3 weeks for up to 16 courses. The pharmacokinetics and metabolism of IFO were measured during its administration, either as a continuous 72 h infusion or as three bolus doses of 3 g/m2 on consecutive days. In 8 patients, the metabolism of IFO was investigated during one early course and one late course to determine the magnitude of any changes following repeated administration. Acute measures of renal toxicity were not correlated with any of the IFO pharmacokinetic or metabolic parameters in the same course, whether the drug was administered as a bolus or by continuous infusion. Chronic renal toxicity, determined 1 month (n = 13) or 6 months (n = 8) after treatment, did not correlate with any of the IFO pharmacokinetic or metabolic parameters in any individual course of treatment. The overall degree of nephrotoxicity, however, was correlated with the changes in metabolism between late and early courses (n = 8). There was a negative correlation between the change in area under the curve of the dechloroethylated metabolites of IFO and the overall nephrotoxicity at 1 month or 6 months after treatment (both r2 = 0.66, P = 0.014). The results imply that patients in whom metabolism via dechloroethylation decreases are at a greater risk of chronic nephrotoxicity. This is contrary to the hypothesis that the systemic production of chloroacetaldehyde is the mechanism by which IFO causes nephrotoxicity. The importance of acute and chronic changes in renal function for long-term outcome remains to be determined.

Acute Disease↗