PubMed Health⌕ Search

Biomedical subjects

J Crawley

Publications and source records attributed to J Crawley.

At least 19 recordsLinked to original sources
PubMed2004

Increased morbidity associated with chronic infection by an epidemic Pseudomonas aeruginosa strain in CF patients.

BACKGROUND: Chronic pulmonary infection with transmissible Pseudomonas aeruginosa strains in individuals with cystic fibrosis (CF) has been reported, raising issues of cross infection and patient segregation. The first such strain to be described (the Liverpool epidemic strain, LES) is now widespread in many UK CF centres. However, whether such infection carries a worse prognosis is unknown. To address this, the clinical course of a group of CF patients chronically infected by LES was compared with that in patients harbouring unique strains. METHODS: Using P aeruginosa strain genotyping, two cohorts of CF patients attending the Liverpool CF service were identified who were LES positive or negative in 1998 and remained so until 2002. From these, two groups of 12 patients were matched in 1998 for age, spirometric parameters, and nutritional state and their clinical course was followed for 5 years. Patients chronically infected with Burkholderia cepacia were excluded. RESULTS: Patients chronically infected with LES had a greater annual loss of lung function than those not chronically infected by LES (mean difference between groups -4.4% (95% CI -8.1 to -0.9; p<0.02)), and by 2002 their percentage predicted forced expiratory volume in 1 second (FEV1) was worse (mean 65.0% v 82.6%, p<0.03). Their nutritional state also deteriorated over the study period (mean difference between groups in body mass index -0.7 (95% CI -1.2 to -0.2; p<0.01)), such that by 2002 they were malnourished compared with LES negative patients (mean BMI 19.4 v 22.7, p<0.02). CONCLUSIONS: Chronic infection with the Liverpool epidemic P aeruginosa strain in CF patients confers a worse prognosis than infection with unique strains alone, confirming the need for patient segregation. Since this strain is common in many CF units, strain identification in all CF centres is essential. This can only be carried out using genomic typing methods.

Body Mass Index↗
PubMed2002

Pharmacokinetics and anticonvulsant effects of diazepam in children with severe falciparum malaria and convulsions.

AIMS: Convulsions are a common complication of severe malaria in children and are associated with poor outcome. Diazepam is used to terminate convulsions but its pharmacokinetics and pharmacodynamics have not been studied in this group. Accordingly, we carried out a comparative study of the pharmacokinetics of intravenous (i.v.) and rectal (p.r.) diazepam. METHODS: Twenty-five children with severe malaria and a convulsion lasting >5 min were studied. Sixteen children received diazepam intravenously (i.v.; 0.3 mg kg(-1)) and nine rectally (p.r.; 0.5 mg kg(-1)). Plasma diazepam concentrations were measured by reversed phase high-performance liquid chromatography. The duration of convulsions, depth of coma, respiratory and cardiovascular parameters were monitored. RESULTS: Median maximum plasma diazepam concentrations of 634 (range 402-1507) ng ml(-1) and 423 (range 112-1953) ng ml(-1) were achieved at 5 and 25 min following i.v. and p.r. administration, respectively. All patients except three (one i.v. and two p.r.) achieved plasma diazepam concentration >200 ng ml(-1) within 5 min. Following p.r. administration, plasma diazepam concentrations were more variable than i.v. administration. A single dose of i.v. diazepam terminated convulsions in all children but in only 6/9 after p.r. administration. However, nine children treated with i.v. and all those treated with p.r. diazepam had a recurrence of convulsions occurring at median plasma diazepam concentrations of 157 (range: 67-169) and 172 (range: 74-393) ng ml(-1) , respectively. All the children in the i.v. and four in the PR diazepam group who had recurrence of convulsions required treatment. None of the children developed respiratory depression or hypotension. CONCLUSIONS: Administration of diazepam i.v. or p.r. resulted in achievement of therapeutic concentrations of diazepam rapidly, without significant cardio-respiratory adverse effects. However, following p.r. administration, diazepam did not terminate all convulsions and plasma drug concentrations were more variable.

Administration, Rectal↗
PubMed2001

Measuring change in quality of life in response to Helicobacter pylori eradication in peptic ulcer disease: the QOLRAD.

This study was designed to determine if a new condition-specific quality of life measure, the Quality Of Life in Reflux And Dyspepsia (QOLRAD), was responsive to clinical change over a four-week period when evaluating peptic ulcer disease patients undergoing Helicobacter pylori (Hp) eradication. A secondary aim was to evaluate QOLRAD's psychometric performance. Hp-positive patients with peptic ulcer disease were recruited from primary care and gastroenterology clinics (N = 155). QOLRAD scores improved significantly (P < 0.0001) and mean total score increase was 1.07 points on a 7-point scale among 111 subjects who responded to Hp eradication. Effect sizes were moderate for responders (0.64) and low for nonresponders (0.36). Score changes below 0.60 were associated with the smallest improvement in patient and physician condition rating; scores above 1.2 were associated with the greatest improvement. The QOLRAD demonstrates reliability and validity. Changes in QOLRAD score can be meaningfully related to clinical changes, aiding evaluation of health-related quality of life in peptic ulcer disease.

Dyspepsia↗
PubMed2001

A comparative trial of paper-and-pencil versus computer administration of the Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire.

BACKGROUND: Although most health-related quality of life questionnaires are self-administered by means of paper and pencil, new technologies for automated computer administration are becoming more readily available. Novel methods of instrument administration must be assessed for score equivalence in addition to consistency in reliability and validity. OBJECTIVES: The present study compared the psychometric characteristics (score equivalence and structure, internal consistency, and reproducibility reliability and construct validity) of the Quality of Life in Reflux And Dyspepsia (QOLRAD) questionnaire when self-administered by means of paper and pencil versus touch-screen computer. The influence of age, education, and prior experience with computers on score equivalence was also examined. RESEARCH DESIGN: This crossover trial randomized 134 patients with gastroesophageal reflux disease to 1 of 2 groups: paper-and-pencil questionnaire administration followed by computer administration or computer administration followed by use of paper and pencil. To minimize learning effects and respondent fatigue, administrations were scheduled 3 days apart. A random sample of 32 patients participated in a 1-week reproducibility evaluation of the computer-administered QOLRAD. RESULTS: QOLRAD scores were equivalent across the 2 methods of administration regardless of subject age, education, and prior computer use. Internal consistency levels were very high (alpha = 0.93-0.99). Interscale correlations were strong and generally consistent across methods (r = 0.7-0.87). Correlations between the QOLRAD and Short Form 36 (SF-36) were high, with no significant differences by method. Test-retest reliability of the computer-administered QOLRAD was also very high (ICC = 0.93-0.96). CONCLUSIONS: Results of the present study suggest that the QOLRAD is reliable and valid when self-administered by means of computer touch-screen or paper and pencil.

Age Factors↗
PubMed2001

Electroencephalographic and clinical features of cerebral malaria.

BACKGROUND: Seizures are a prominent feature of childhood cerebral malaria, and are associated with an increased risk of death and neurological sequelae. We present the electroencephalographic (EEG) findings from a detailed clinical and electrophysiological study. METHODS: Children with cerebral malaria had EEGs recorded within six hours of admission, and at 12 hourly intervals until recovery of consciousness. Ten deeply comatose children underwent intracranial pressure monitoring. Children were not mechanically ventilated, which made it possible to directly correlate the clinical and EEG findings. RESULTS: Of 65 children aged 9 months and above, 40 had one or more seizures, and 18 had an episode of status epilepticus. Most seizures were partial motor, and spike wave activity consistently arose from the posterior temporo-parietal region, a border zone area lying between territories supplied by the carotid and vertebrobasilar circulations. Fifteen children had seizures that were clinically subtle or electrographic. Clinical seizures were associated with an abrupt rise in intracranial pressure. Fifty children recovered fully, seven died, and eight had persistent neurological sequelae. Initial EEG recordings of very slow frequency, or with background asymmetry, burst suppression, or interictal discharges, were associated with an adverse outcome. CONCLUSIONS: Serial EEG recording has uncovered a range of clinical, subtle, and electrographic seizures complicating childhood cerebral malaria, and has emphasised their importance in the pathogenesis of coma. Further work is required to determine the most appropriate regimen for the prophylaxis and treatment of seizures in cerebral malaria, in order to improve outcome.

Analysis of Variance↗
PubMed2000

Effect of phenobarbital on seizure frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study.

BACKGROUND: Seizures commonly complicate cerebral malaria and are associated with an increased risk of death and neurological sequelae. We undertook a randomised study to assess the efficacy of intramuscular phenobarbital in preventing seizures in childhood cerebral malaria. METHODS: Children with cerebral malaria admitted to one hospital in Kilifi, Kenya, were randomly assigned a single intramuscular dose of phenobarbital (20 mg/kg) or identical placebo. Clinical tolerance was assessed at the start of the trial, with particular reference to respiratory depression and hypotension. Seizures were timed and recorded, and treated in a standard way. Plasma phenobarbital concentrations were measured. Analyses were by intention to treat. FINDINGS: 440 children with cerebral malaria were admitted to the hospital; 100 were not recruited to the study. Of the remaining 340, 170 received phenobarbital and 170 placebo. The drug was adequately absorbed and well tolerated. Seizure frequency was significantly lower in the phenobarbital group than in the placebo group (18 [11%] vs 46 [27%] children had three or more seizures of any duration; odds ratio 0.32 [95% CI 0.18-0.58]) but mortality was doubled (30 [18%] vs 14 [8%] deaths; 2.39 [1.28-4.64]). The frequency of respiratory arrest was higher in the phenobarbital group than in the placebo group, and mortality was greatly increased in children who received phenobarbital plus three or more doses of diazepam (odds ratio 31.7 [1.2-814]). INTERPRETATION: In children with cerebral malaria, phenobarbital 20 mg/kg provides highly effective seizure prophylaxis but is associated with an unacceptable increase in mortality. Use of this dose cannot, therefore, be recommended.

Adolescent↗
PubMed2000

Chloroquine is not a risk factor for seizures in childhood cerebral malaria.

OBJECTIVES: There are a number of case reports in the medical literature suggesting an association between the ingestion of chloroquine and subsequent seizure activity. Our study was designed to investigate the relationship between blood levels of chloroquine (CQ), its metabolite desethylchloroquine (DCQ), and seizures in children admitted to hospital with cerebral malaria. METHODS: Serial blood levels of CQ and DCQ were measured over the first 24 h of hospital admission in children with cerebral malaria. The number and duration of all seizures was recorded, and statistical analysis subsequently performed to determine the relationship between seizure activity and blood concentrations of CQ and DCQ. RESULTS: Chloroquine was detected in 92% (100/109) of admission blood samples. 54% (59/109) of the patients had one or more seizures after admission, while 8% (9/109) had an episode of status epilepticus. Median (interquartile range) baseline concentrations of CQ and DCQ were, respectively, 169.4 microg/ml (75.1-374.9) and 352.3 microg/ml (81.9-580.1) for those children who had seizures after admission, compared to CQ 227.5 microg/ml (79.4-430.2) and DCQ 364.0 microg/ml (131.3-709.4) for those who did not have seizures (P > 0.5 for all comparisons). Baseline concentrations of CQ and DCQ were not significantly associated with the occurrence of seizures lasting for 5 min or more. The nine children who had an episode of status epilepticus had significantly lower median admission levels of CQ than those without status epilepticus: 75.1 microg/l (7.4-116.5) vs. 227.5 microg/l (85.6-441.2), P = 0.02. Multivariate logistic regression analysis, taking into account factors likely to affect the risk of seizures in hospital, failed to change the significance of these results. CONCLUSIONS: These findings suggest that chloroquine does not play an important role in the aetiology of seizures in childhood cerebral malaria.

Adolescent↗
PubMed2000

Expression, localization, and activity of tissue factor pathway inhibitor in normal and atherosclerotic human vessels.

Tissue factor (TF) pathway inhibitor (TFPI) is the major downregulator of the procoagulant activity of the TF-factor VIIa (FVIIa) complex (TF. FVII). The active TF present in the atherosclerotic vessel wall is proposed to be responsible for the major complication of primary atherosclerosis, namely, acute thrombosis after plaque rupture, but our knowledge of the sites of TFPI expression in relation to TF remains fragmentary. The aim of this study was to investigate the expression, localization, and activity of TFPI and its relation to the activity and distribution of TF in the normal and atherosclerotic vessel wall. We applied a novel approach in which serial cross sections of human vascular segments were used to perform a complete set of assays: immunolabeling for TFPI and/or TF, in situ hybridization for the expression of TFPI mRNA, ELISA for the determination of TFPI antigen, and functional assay for the activity of TFPI and TF. In healthy vessels, TFPI protein and mRNA are present in luminal and microvascular endothelial cells (ECs) and in the medial smooth muscle cells (SMCs). In atherosclerotic vessels, TFPI protein and mRNA frequently colocalized with TF in ECs overlying the plaque and in microvessels, as well as in the medial and neointimal SMCs, and in macrophages and T cells in areas surrounding the necrotic core. At the ultrastructural level, immunogold electron microscopy confirmed the localization of TFPI in ECs, macrophages/foam cells, and SMCs. In ECs and SMCs, the gold particles decorated the plasmalemma proper and the caveolae. ELISA on cross sections revealed that atherosclerotic tissues contain more TFPI than do the healthy vessels. TFPI was functionally active against TF. FVIIa-induced coagulation, and its activity was higher in those tissues that display less TF. The largest amount of TFPI and TF were detected in complicated arterial plaques. By immunofluorescence, TFPI colocalized with platelet- and fibrin-rich areas within the organized thrombi. Atherosclerotic vessel sections promote activation of factor X, which is dependent on the presence of TF and enhanced by preincubation of the sections with anti-TFPI IgG. Taken altogether, our results suggest that TFPI is largely expressed in the normal vessel wall and enhanced in the atherosclerotic vessel, in a manner suggesting a significant role of TFPI in the regulation of TF activity.

Arteriosclerosis↗
PubMed2000

Cerebrospinal fluid studies in children with cerebral malaria: an excitotoxic mechanism?

The pathogenesis of cerebral malaria is poorly understood. One hypothesis is that activation of microglia and astrocytes in the brain might cause the cerebral symptoms by excitotoxic mechanisms. Cerebrospinal fluid was sampled in 97 Kenyan children with cerebral malaria, 85% within 48 hr of admission. When compared with an age-matched reference range, there were large increases in concentrations of the excitotoxin quinolinic acid (geometric mean ratio cerebral malaria/reference population [95% confidence limits] = 14.1 [9.8-20.4], P < 0.001) and total neopterin (10.9 [9.1-13.0], P < 0.001) and lesser increases in tetra-hydrobiopterin, di-hydrobiopterin, and 5-hydroxyindoleacetic acid. There was no change in tryptophan concentration. In contrast, nitrate plus nitrite concentrations were decreased (geometric mean ratio = 0.45 [0.35-0.59], P < 0.001). There was a graded increment in quinolinic acid concentration across outcome groups of increasing severity. The increased concentration of quinolinic acid suggests that excitotoxic mechanisms may contribute to the pathogenesis of cerebral malaria.

Antimalarials↗
PubMed1998

Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice.

The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked human genetic disorder characterized by mental retardation, congenital cataracts, and renal tubular dysfunction. The Lowe syndrome gene, OCRL1, encodes a phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi complex. The pathogenesis of Lowe syndrome due to deficiency of a phosphatidylinositol 4,5-bisphosphate 5-phosphatase in the Golgi complex is unknown. We have used targeted disruption in embryonic stem cells to make mice deficient in Ocrl1, the mouse homologue for OCRL1, as an animal model for the disease. Surprisingly, mice deficient in Ocrl1 do not develop the congenital cataracts, renal Fanconi syndrome, or neurological abnormalities seen in the human disorder. We hypothesized that Ocrl1 deficiency is complemented in mice by inositol polyphosphate 5-phosphatase (Inpp5b), an autosomal gene that encodes a phosphatidylinositol bisphosphate 5-phosphatase highly homologous to Ocrl1. We created mice deficient in Inpp5b; the mice were viable and fertile without phenotype except for testicular degeneration in males beginning after sexual maturation. We crossed mice deficient in Ocrl1 to mice deficient in Inpp5b. No liveborn mice or embryos lacking both enzymes were found, demonstrating that Ocrl1 and Inpp5b have overlapping functions in mice and suggesting that the lack of phenotype in Ocrl1-deficient mice may be due to compensating Inpp5b function.

Amino Acid Sequence↗
PubMed1998

Reliability and validity of the Gastrointestinal Symptom Rating Scale in patients with gastroesophageal reflux disease.

The objective of this study was to evaluate the reliability and validity of the gastrointestinal Symptom Rating Scale (GSRS) in US patients with gastroesophageal reflux disease (GERD). Five hundred and sixteen adults with predominant heartburn symptoms of GERD were recruited from gastroenterologist and family physician practices and treated with 6 weeks of 150 mg ranitidine twice daily to identify poorly responsive symptomatic GERD. The GSRS, the Medical Outcomes Study Short Form-36 (SF-36) Health Survey and the Psychological General Well-being (PGWB) scale were administered at baseline and after 6 weeks of treatment. Reported ratings of GERD-related symptoms from physician and patient diaries were measured. The GSRS contains five scales: reflux syndrome, abdominal pain, constipation syndrome, diarrhoea syndrome and indigestion syndrome. The internal consistency reliabilities for the GSRS scales ranged from 0.61 to 0.83 and the intraclass correlation coefficients ranged from 0.42 to 0.60. The GSRS scale scores were correlated with the SF-36 and PGWB scales and with the number and severity of heartburn symptoms. Patients with two or three clinician-rated GERD-related symptoms reported worse GSRS scale scores compared with patients with fewer symptoms (p < 0.0001). Statistically significant differences in the mean GSRS scale scores were observed between treatment responders and non-responders (p < 0.0001) and patients showing a response to treatment had larger mean changes in their GSRS scales than patients not showing a response to treatment (p < 0.0001). The standardized response means ranged from 0.42 to 1.43 for the GSRS scale scores. It was concluded that the GSRS is a brief, fairly comprehensive assessment of common gastrointestinal symptoms. The GSRS has good reliability and construct validity and the GSRS scales discriminate by GERD symptom severity and are responsive to treatment. The GSRS is a useful patient-rated symptom scale for evaluating the outcomes of treatment for GERD.

Adult↗
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↗
PubMed1997

Urokinase but not tissue plasminogen activator mediates arterial neointima formation in mice.

To define the role of the plasminogen activators (PAs) tissue PA (t-PA) and urokinase PA (u-PA) in vascular wound healing, neointima formation and reendothelialization were evaluated after electric or mechanical arterial injury in mice with a single or combined deficiency of t-PA (t-PA-/-) and/or u-PA (u-PA-/-). In both models, neointima formation and neointimal cell accumulation were reduced in u-PA-/- and in t-PA-/-/u-PA-/- arteries but not in t-PA-/- arteries. The electric injury model was used to characterize the underlying cellular mechanisms. Topographic analysis of vascular wound healing in electrically injured wild-type and t-PA-/- arteries revealed a similar degree of migration of smooth muscle cells from the noninjured borders into the necrotic center. In contrast, in u-PA-/- and t-PA-/-/u-PA-/- arteries, smooth muscle cells accumulated at the uninjured borders but failed to migrate into the necrotic center. Cultured u-PA-/- but not t-PA-/- smooth muscle cells also failed to migrate in vitro after scrape wounding. Proliferation of smooth muscle cells was not affected by PA deficiency. Reendothelialization after electric injury was similar in all genotypes. In situ analysis revealed markedly elevated u-PA zymographic activity, mRNA, and immunoreactivity in smooth muscle cells, endothelial cells, and leukocytes within 1 week after injury, eg, when cells migrated into the wound. Thus, u-PA plays a significant role in vascular wound healing and arterial neointima formation after injury, most likely by affecting cellular migration.

Animals↗
PubMed1996

Non-invasive measurement of cardiac oxygenation and haemodynamics during transient episodes of coronary artery occlusion and reperfusion in the pig.

1. The non-invasive method of near-infrared spectroscopy was used to measure myocardial oxygenation and haemodynamics in response to left anterior descending coronary artery occlusion in a porcine model. 2. Near-infrared spectroscopy measures changes in haemoglobin (and myoglobin) oxygenation and blood volume to yield information on tissue perfusion and flow. It also measures the redox state of cytochrome aa3, thus providing information about intracellular oxygen utilization. 3. Left anterior descending coronary artery occlusion was induced to produce periods of ischaemia lasting between 24s and 13.5 min (n = 13). The changes in deoxyhaemoglobin, oxyhaemoglobin and cytochrome aa3 measured during occlusion were all highly significant compared with baseline variation. In all occlusions (n = 13) a rapid decrease in oxyhaemoglobin concentration (-75.83 +/- 3.27 mumol/l, mean +/- SEM) with a simultaneous increase in deoxyhaemoglobin of 9.27 +/- 1.69 mumol/l was measured. The total haemoglobin concentration also fell by -71.3 +/- 5.32 mumol/l. Cytochrome aa3 was also reduced during occlusion (-8.35 +/- 1.044) mumol/l. 4. Over the range 24-60s occlusion, the magnitude of the fall in total haemoglobin and oxyhaemoglobin correlated with the duration of occlusion (P < 0.003 and 0.013 respectively). For total haemoglobin only the magnitude of the fall correlated with the increase upon release of occlusion (r = 0.89, P < 0.003). 5. Release of occlusion (n = 8) resulted in an immediate increase in the concentration of deoxyhaemoglobin at 9.88 +/- 1.06s, then total haemoglobin at 13.62 +/- 1.23s and finally oxyhaemoglobin at 29.75 +/- 5.96s. The difference between the timing of the maxima after reperfusion is significant (P < 0.002 and P < 0.007 respectively). Moreover, the time for the deoxyhaemoglobin signal to reach maximum values was found to correlate with the duration of occlusion (P < 0.04). This could be indicative of the PO2 of the ischaemic tissues and an immediate off-loading of oxygen from oxyhaemoglobin. The results are reliable, reproducible and sensitive enough to detect the kinetics of haemoglobin oxygenation from a beating heart in situ.

Animals↗
PubMed1996

The pathogenesis of severe malaria in African children.

The pathogenesis of severe, Plasmodium falciparum malaria in African children is considered in the context of its two major clinical syndromes: malaria with respiratory distress; and malaria with neurological disturbance. Respiratory distress is an important prognostic marker in children with P. falciparum infections. In the majority of cases it reflects an underlying metabolic acidosis, usually associated with lactic acidaemia. Hypovolaemia and anaemia are important underlying factors. The syndrome of malaria with neurological impairment is not a homogenous condition. Four distinct groups of children fulfilling the WHO definition of cerebral malaria may be distinguished: (1) prolonged post-ictal state; (2) covert status epilepticus; (3) severe metabolic derangement (particularly hypoglycaemia and metabolic acidosis); and (4) children with a primary neurological syndrome. These distinctions are important from a therapeutic point of view, as well as for their implications for studies on underlying pathogenic factors. A simple framework is presented to summarize how three major processes, anaemia, the acute phase response and sequestration of infected cells, may interact to lead to reduced tissue oxygenation as a unifying process in the pathogenesis of both major clinical syndromes of severe malaria.

Acute Disease↗
PubMed1996

Seizures and status epilepticus in childhood cerebral malaria.

Prolonged, multiple seizures complicate a high proportion of cases of childhood cerebral malaria, and several studies have shown an association between these and neurological sequelae. We prospectively studied 65 patients (38 female) admitted to Kilifi Hospital in 1994. Electroencephalographic recordings (EEGs) were made at 12-hourly intervals, with continuous recordings made on a cerebral function analysing monitor (CFAM). Survivors were seen one month after discharge. Cerebral computerized tomography was performed on children with neurological sequelae. Sixty-two percent of patients had seizures following admission, of whom half had an episode of status epilepticus. Fifty-two percent of seizures were partial motor, 34% generalized tonic-clonic, and 14% partial with secondary generalization. In 22%, coma appeared to be due to a prolonged postictal state. Ten children had subtle motor seizures. Posterior parieto-temporal discharges were the most common EEG finding. Seven children died, eight developed neurological sequelae, and 50 (77%) recovered fully. Status epilepticus was associated with the development of neurological sequelae. Prolonged, multiple seizures may play an important part in the pathogenesis of coma in childhood cerebral malaria, and are likely to contribute to both the morbidity and mortality of this disease.

Brain↗
PubMed1996

Deep breathing in children with severe malaria: indicator of metabolic acidosis and poor outcome.

Despite the frequent association of respiratory symptoms and signs with malarial morbidity and mortality in sub-Saharan Africa, the value of individual symptoms and signs has rarely been assessed. We have prospectively examined the association of individual clinical findings with the summary diagnosis of respiratory distress, outcome, and the presence of metabolic acidosis in children admitted with severe malaria to a Kenyan district hospital. Respiratory distress was present in 119 of the 350 children included in the study and in 23 of the 30 deaths (relative risk = 6.5, 95% confidence interval = 2.8-14.4). The features of a history of dyspnea, nasal flaring, and indrawing or deep breathing (Kussmaul's respiration) were individually most closely associated with the summary diagnosis of respiratory distress. Of these, deep breathing, which was sensitive (91%) and specific (83%) for the presence of severe metabolic acidosis (base excess < or = -12), is the best candidate sign to represent the prognostically important syndrome of malarial respiratory distress. Therefore, it warrants further prospective evaluation in different clinical settings and areas of different malaria endemicity.

Acidosis↗