HIV infection and foreign travel.
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Biomedical subjects
Publications and source records attributed to C J Ellis.
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The cytolytic capacity of mycobacterial antigen-stimulated peripheral blood mononuclear cells, from healthy Mantoux-positive volunteers and from patients with tuberculosis was investigated. Polyclonal T cell lines induced by 7 days of stimulation in vitro with PPD or a sonicate of Mycobacterium tuberculosis lysed both autologous macrophages and Epstein-Barr virus (EBV) transformed B cell lines which had been pulsed with mycobacterial antigens, to a greater extent than unpulsed target cells or target cells pulsed with an irrelevant antigen (streptokinase/streptodornase). The killing of mycobacterial antigen-pulsed macrophages and EBV-transformed B cell line targets was inhibited by monoclonal antibodies to MHC class II antigens but not by antibodies directed against MHC class I antigens. PPD-pulsed EBV-transformed lymphoblastoid cell lines (LCL) competitively inhibited the killing of mycobacterial antigen-pulsed macrophages, whereas natural killer (NK) sensitive K562 cells (with or without antigen pulsing) did not inhibit mycobacterial antigen-dependent cytolysis of macrophages. Patients with tuberculosis showed a spectrum of mycobacterial antigen-induced cytolytic capacity. Those with extensive tissue necrosis (e.g. cavitatory pulmonary tuberculosis or caseous, extrathoracic tuberculosis) had high levels while patients with disseminated (miliary) tuberculosis or disease refractory to treatment showed little evidence of mycobacterial antigen induced cytotoxicity. The ability of mycobacterial antigen-stimulated lymphoblasts to kill specific antigen-pulsed autologous macrophages was not significantly different between healthy donors and patients with tuberculosis. However, the 'mycobacterial antigen-specific' component of this cytolysis was significantly deficient (P less than 0.01) in patients. We conclude that mycobacterial antigen-specific cytotoxic T cell responses may play a significant part in the immune response to mycobacterial infection.
In this multicentre study a controlled-release formulation of levodopa and the decarboxylase inhibitor benserazide (Madopar CR) was evaluated in patients with Parkinson's disease exhibiting dose-related fluctuations in motor performance in response to conventional levodopa preparations. The effect of Madopar CR, with or without conventional levodopa/benserazide, on the proportion of time spent "on", "off" or "intermediate" was compared with that of previous conventional levodopa/decarboxylase inhibitor therapy. Evaluation of the two periods of optimum therapy was based on both patient diary data and investigator opinion. Forty seven patients completed the study but full patient diaries were available for only 37. The mean optimum total daily dosage of conventional Madopar was 820 mg taken in a mean of 6.4 doses, compared with a mean optimum daily dosage of combined Madopar CR and conventional Madopar of 1088 mg, taken in a mean of 5.2 doses. Conventional Madopar was taken in addition to Madopar CR in all but eight patients. Madopar CR was felt to be advantageous in 83% and disadvantageous in 11% of patients completing the study. Considering the 37 patients for whom diary data were available, Madopar CR therapy resulted in an increase in the mean time spent "on" (p = 0.016) and a decrease in the mean time spent "off" (p = 0.029) compared with conventional Madopar alone. Individually 25 out of 37 had an increase in "on" time and 19 out of 37 experienced a decrease in "off" time. Thus Madopar CR was found to be beneficial in a significant proportion of patients experiencing fluctuations in response to conventional levodopa.
A 52 year old man presented with myoglobinuria-induced acute renal failure requiring dialysis. Despite renal biopsy, the cause of the myoglobinuria was not established until he re-presented a year later with a milder episode. At this stage investigations, including a muscle biopsy, demonstrated a defect in fatty acid oxidation amenable to dietary and lifestyle advice. This report emphasizes the importance of reaching a definitive diagnosis in myoglobinuria.
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Antibiotics have an important place in the management of gastrointestinal disease. Recent studies have demonstrated efficacy in acute bacterial gastroenteritis caused by salmonellae and campylobacteriaceae, shigellae and enterotoxigenic strains of E coli (ETEC). Tetracycline remains effective in cholera. Antibiotic resistance is widespread amongst the enteric pathogens and can quickly spread during epidemics of infective diarrhoeas. It is important that antibiotics are reserved for the treatment of serious infections lest their effectiveness in these conditions be lost. Campylobacter pylori appears to be an important cause of chronic active gastritis and is amenable to treatment with antibiotics and bismuth salts. The role of C. pylori in the pathogenesis of peptic ulcer disease is not yet established but there is mounting evidence that antibiotic treatment will have a place in the treatment of this common condition. The effect of antibiotics on the normal intestinal microflora can have serious consequences. It is a major cause of resistance in urinary tract pathogens, can result in outbreaks of hospital infection with resistant organisms and frequently results in C. difficile associated diarrhoea.
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New technology is allowing the development of more effective and safer vaccines to replace old vaccines and provide protection against a wider range of diseases. The worldwide priority, however, must be to increase the uptake of existing vaccines to reduce childhood mortality and morbidity.
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Virtually all CO production in humans and animals is thought to result from the catabolism of heme, and endogenous CO production (VCO) is used as a measure of heme turnover. Using a rebreathing technique, we found that previously fed mice had an apparent VCO that was 40% greater than that of mice that had been fasted before the study. This unexpected result was shown to reflect an excess CO production by the excreta (feces, urine, or both) of fed mice relative to the excreta of fasted mice. Incubation of feces and urine of humans, rats, and mice demonstrated CO release that was not inhibited by autoclaving or acidification to pH 1. CO release from excreta was markedly reduced, however, under anaerobic conditions, and fed and fasted animals excreted CO at the same rate when their excreta were maintained in an anaerobic state. We conclude that feces and urine can release CO via nonenzymatic, oxidative reactions and, under some circumstances, this source of CO can influence measurements of VCO.
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Breath hydrogen tests are limited by leak of gases from breath samples from standard glass or plastic syringes. These losses may be substantial when these samples are stored for long periods of time. We describe a simple manipulation involving the use of a mineral oil or water seal at the end of the syringe barrel that markedly reduces the leakage of H2 and other gases to negligible levels.
Shigella usually causes a self-limited infection which untreated lasts on average seven days (range one to 30 days). We report a patient who had persistent symptoms for 10 months caused by Shigella flexneri which was finally identified on cultures from a rectal swab.
The presence of macroamylasemia can be suspected when a patient has low renal clearance of amylase relative to creatinine (Cam/Ccr). However, the Cam/Ccr is seldom reduced to the extent expected given the fraction of amylase that appears to be bound in the macroamylase complex by gel filtration studies at 3 degrees C. Therefore, we tested the possibility that the binding of amylase in macroamylase complexes was temperature dependent and that binding at physiological temperatures might be less than at 3 degrees C. Gel filtration of five macroamylase-containing sera was carried out at temperatures of 3 degrees, 25 degrees, 37 degrees, 43 degrees, and 49 degrees C. Binding of amylase in the complex decreased as the temperature increased with virtually all amylase bound at 3 degrees C and virtually no amylase bound at 49 degrees C. The fraction of the amylase that bound at 37 degrees C was approximately what would have been predicted from the Cam/Ccr of each of the five subjects. We conclude that amylase binding in macroamylase complexes is extremely temperature sensitive and appreciable changes in binding may occur over the physiological temperature range of 37-41 degrees C.
Five patients with isolated optic neuropathy and sarcoidosis are discussed. The spectrum of clinical disease was variable but two groups could be identified: patients with chronic progressive visual loss which was associated with thickening of the optic nerve and was refractory to steroid treatment, and patients with acute or subacute optic neuropathy in which the visual loss responded rapidly to steroids. In the latter group steroid dependence developed in all three of the patients. In none did the clinical picture resemble that of the optic neuritis associated with multiple sclerosis.