Biomedical subjects
M English
Publications and source records attributed to M English.
Two blind randomized cross-over trials in the treatment of primary open angle glaucoma.
We present the results of two blind randomized trials comparing both guanethidine 3 per cent and adrenaline 0.5 per cent (Ganda 3.0/0.5) and guanethidine 1 per cent and adrenaline 0.2 per cent (Ganda 1.0/0.2) in single drop form with Timolol (Timoptol) 0.25 per cent. Results of 48-hour phasing at the end of one month's treatment demonstrated a significantly greater fall in intraocular pressure with Ganda 3.0/0.5 (9.8 mm Hg) than with Timolol 0.25 per cent (7.67 mm Hg) P less than 0.001. There was no significant difference in the fall in intraocular pressure between Ganda 1.0/0.2 (8.87 mm Hg) and Timolol 0.25 per cent (8.24 mm Hg).
Erythromycin ointment for ocular prophylaxis of neonatal chlamydial infection.
We compared the efficacy of erythromycin ophthalmic ointment vs 1% silver nitrate drops for the prevention of neonatal conjunctivitis or respiratory tract infection from Chlamydia trachomatis. The organism was isolated from the cervix of 67 (12%) of 572 pregnant women. They gave birth to 559 infants who were randomly assigned to either prophylaxis immediately after birth. Thirty-six of 60 infants born to Chlamydia-positive women received silver nitrate; 24 received erythromycin. Twelve (33%) of the 36 infants who received silver nitrate had chlamydial conjunctivitis, but none of the 24 infants who received erythromycin did. Ten (29%) of 36 infants receiving silver nitrate had chlamydial nasopharyngeal infection (three later had pneumonia), as opposed to five (21%) of 24 who received erythromycin (one had pneumonia). Thus, erythromycin ointment is effective in prevention of chlamydial conjunctivitis, but it may not reduce nasopharyngeal infection or subsequent pneumonia.
Structural changes in simian virus 40 chromatin as probed by restriction endonucleases.
The structure of simian virus 40 (SV40) chromatin was probed by treatment with single- and multiple-site bacterial restriction endonucleases. Approximately the same fraction of the chromatin DNA was cleaved by each of three different single-site endonucleases, indicating that the nucleosomes do not have unique positions with regard to specific nucleotide sequences within the population of chromatin molecules. However, the extent of digestion was found to be strongly influenced by salt concentration. At 100 mM NaCl-5 mM MgCl2, only about 20% of the simian virus 40 (SV40) DNA I in chromatin was converted to linear SV40 DNA III. In contrast, at lower concentrations of NaCl (0.05 or 0.01 M), an additional 20 to 30% of the DNA was cleaved. These results suggest that at 100 mM NaCl only the DNA between nucleosomes was accessible to the restriction enzymes, whereas at the lower salt concentrations, DNA within the nucleosome regions became available for cleavage. Surprisingly, when SV40 chromatin was digested with multiple-site restriction enzymes, less than 2% of the DNA was digested to limit digest fragment, whereas only a small fraction (9 to 15%) received two or more cuts. Instead, the principal digest fragment was full-length linear SV40 DNA III. The failure to generate limit digest fragments was not a consequence of reduced enzyme activity in the reaction mixtures or of histone exchange. When the position of the principal cleavage site was mapped after HpaI digestion, it was found that this site was not unique. Nevertheless, all sites wree not cleaved with equal probability. An additional finding was that SV40 chromatin containing nicked-circular DNA II produced by random nicking of DNA I was also resistant to digestion by restriction enzymes. These results suggest that the initial cut which causes relaxation of topological constraint in SV40 chromatin DNA imparts resistance to further digestion by restriction enzymes. We propose that this may be accomplished by either "winding" of the internucleosomal DNA into the body of the nucleosome, or as suggested by others, by successive right-hand rotation of nucleosomes.
Ly phenotypes and MHC recognition: the allohelper that recognizes K or D is a mature Ly123 cell.
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Cardiopulmonary adjustments following single high dosage administration of methylprednisolone in traumatized man.
Pharmacologic doses of methylprednisolone sodium succinate were administered to 10 critically ill patients when the steroid was the only variable. Measurements of respiratory and circulatory physiologic parameters were obtained in all patients prior to injection and at 30 and 90 minutes following injection of methylprednisolone sodium succinate. A significant increase in Cardiac Index was seen (P less than .01) which appeared to be in association with a decrease in pulmonary vascular resistance (P less than .01) at a time when physiologic shunting of blood through the lungs increased (P less than .01). These changes imply improved perfusion of non- or poorly ventilated portions of the lungs. Four of ten patients demonstrated removal of lactate by the lung during the control period. Following methylprednisolone sodium succinate injection, 9 of 10 patients demonstrated production or a washout of lactate from the lungs.
Correlation of pulmonary wedge and left atrial pressures. A study in the patient receiving positive end expiratory pressure ventilation.
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Physiologic consequences of positive end-expiratory pressure (PEEP) ventilation.
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Life-threatening severe malarial anaemia.
Despite our improved understanding of the pathophysiology of severe malaria, major changes in clinical management have not been forthcoming. However, in the case of life-threatening severe malarial anaemia, preliminary evidence suggests that changes in current clinical practice rather than the introduction of novel interventions may improve child survival. This review argues that further research into the clinical physiology of this syndrome is required and could provide compelling evidence for changes in practice particularly with regard to blood transfusion. We focus on the syndrome of severe, symptomatic malarial anaemia associated with a metabolic acidosis which has a high fatality rate. However, it should be remembered that a far greater number of children without signs of life-threatening disease nonetheless experience significant morbidity from severe anaemia. Many of these less-severely ill children may also require blood transfusion. However, the mode and rationale for transfusion in this less-severely ill group is specifically not addressed. Indeed, the arguments presented should not be extrapolated to suggest a uniform approach to transfusion is warranted, the role of blood in the less-critically ill child with severe malaria anaemia being a further area that requires urgent research.
An open randomized trial of artemether versus quinine in the treatment of cerebral malaria in African children.
We have compared the efficacy of artemether versus quinine as treatment for cerebral malaria in children in an open randomized clinical trial in Kenya. Children admitted to hospital with coma and Plasmodium falciparum parasitaemia were treated with either intramuscular artemether (3.2 mg/kg loading dose followed by 1.6 mg/kg daily) or intravenous quinine (20 mg/kg loading dose followed by 10 mg/kg every 8 h). Both drugs were well tolerated and no significant adverse effect was observed. Parasite clearance times (50% and 90%) were shorter in patients treated with artemether (median times [h], with interquartile ranges in brackets, were: 50%, 7.3 [4.2-12.4] vs. 15.5 [9-22]; 90%, 16.9 [13.2-25] vs. 28.5 [22-35]; P < 0.0001). The total mortality in 160 children with cerebral malaria was 16.25%, with no overall significant difference between the 2 treatment groups. In a subgroup of children with respiratory distress, mortality was higher in those treated with artemether (43.7% vs. 11.1%, P < 0.05). The frequency of neurological sequelae and clinical recovery times were similar in both treatment groups. We conclude that there would currently be no advantage in replacing quinine with artemether for the treatment of cerebral malaria in African children.
Clinical overlap between malaria and severe pneumonia in Africa children in hospital.
Data collected from 200 children admitted to a hospital on the Kenyan coast who met a broad definition of severe acute respiratory infection (ARI) indicated that simple clinical signs alone are unable absolutely to distinguish severe ARI and severe malaria. However, laboratory data showed that marked differences exist in the pathophysiology of unequivocal malaria and unequivocal ARI. Children in the former group had a higher mean oxygen saturation (97 vs. 94, P < 0.001), mean blood urea level (5.3 vs. 1.9 mmol/L, P < 0.001) and geometric mean lactate level (4.5 vs. 2.1 mmol/L, P < 0.001), and lower mean haemoglobin level (5.3 vs. 9.0 g/dL, P < 0.001) and base excess (-9.4 vs. -2.6, P < 0.001) than those in the latter group. Using these discriminatory variables it was estimated that up to 45% of children admitted with respiratory signs indicative of severe ARI probably had malaria as the primary diagnosis. Radiological examination supported this conclusion, indicating that pneumonia characterized by consolidation was uncommon in children with respiratory signs and a high malarial parasitaemia (> or = 10,000/microliters). There is no specific radiological sign of severe malaria. In practice, all children with respiratory signs warranting hospital admission in a malaria endemic area should be treated for both malaria and ARI unless blood film examination excludes malaria. In those with malaria and clinical evidence of acidosis, but no crackles, antibodies may be withheld while appropriate treatment for dehydration and anaemia is given. However, if clinical improvement is not rapid, antibiotics should be started.
The disposition of intramuscular artemether in children with cerebral malaria; a preliminary study.
The disposition of intramuscular artemether (AM) was studied in 26 Kenyan children with cerebral malaria. Antimalarial activity determined by bioassay was compared with total plasma AM plus dihydroartemisinin (DHA) determined by high power liquid chromatography (HPLC). Therapeutic levels were achieved in most subjects (21/26) within 1 h of receiving intramuscular AM (3.2 mg/kg), with close correlation between bioassay and HPLC measurements (r = 0.706). However, there was marked inter-individual variation, antimalarial activity was undetectable in 5 subjects ('non-absorbers'), and plasma concentrations were lower in subject with respiratory distress. The 50% parasite clearance time was significantly longer in non-absorbers (mean = 13.1 h, SD = 10.8 vs. mean = 7.8 h, SD = 5.5; P = 0.013). We conclude that the bioavailability of intramuscular AM in children with severe malaria may be highly variable, particularly in the presence of respiratory distress, and may be associated with an inadequate therapeutic response.
Abnormal respiratory patterns in childhood cerebral malaria.
Of 295 children with cerebral malaria, 117 (40%) had an abnormal respiratory pattern; 15 children exhibited more than one pattern during their clinical course. Four distinct patterns were seen. (i) Deep breathing (80 children); this was associated with severe metabolic acidosis, and resolved following treatment with intravenous fluids and/or blood. (ii) Hypoventilation with nystagmus and salivation (18 children); simultaneous electroencephalographic recording revealed continuous electrical seizure activity, demonstrating that these children were in subtle status epilepticus; anticonvulsant treatment resulted in return to normal of blood gases and recovery of consciousness. (iii) Hyperventilation with extensor posturing (20 children), which was associated with varying degrees of intracranial hypertension. (iv) Periodic respiration (14 children); all had clinical features suggestive of transtentorial herniation, and died following a respiratory arrest. Abnormal respiratory patterns can alert the clinician to complications of cerebral malaria that require treatment. Recognition of these patterns and rapid initiation of appropriate supportive therapy may help to reduce the high mortality rate of this disease.
Longitudinal studies on chlamydial infections in the first year of life.
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Ophthalmia neonatorum associated with maternal chlamydial infections.
An unselected sample of 142 pregnant women had a single cervical culture for C trachomatis at 36 to 40 weeks' gestation. Of these women, 18 (12.7%) had positive cultures, and their infants were followed in postoperative fashion. Of these 18 infants, eight (44%) developed ophthalmia neonatorum. A combination of cultures and conjunctival smears for Giemsa staining and fluorescent-antibody examination for infected cells confirmed the diagnosis in 70% of the infants with conjunctivitis. However, 12 of 18 infants has serum antibodies against genital strain chlamydial antigens at 1 year of age, indicating that a majority of the infants were infected. Four of the infants had superior micropannus at 1 year of age; however, none of the infants had active conjunctivitis nor corneal or conjunctival scars.