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Biomedical subjects

C J Ellis

Publications and source records attributed to C J Ellis.

At least 19 recordsLinked to original sources

A further British case of growth hormone induced Creutzfeldt-Jakob disease.

Transmission of Creutzfeldt-Jakob disease (CJD) from cadaveric growth hormone injections had previously been reported in 7 cases, including one from Britain. As a result, the treatment was abandoned in 1985 and superceded by safer recombinant DNA growth hormone injections. Recent reports now record the number of cases worldwide as 23, but with the incubation period being measured in years, new cases of CJD can still present. We give a detailed report of one of the recent cluster of British cases and aim to highlight the problem to clinicians who may encounter further patients with cadaveric growth hormone induced CJD.

Adult

Generation of cytolytic T cells in individuals infected by Mycobacterium tuberculosis and vaccinated with BCG.

BACKGROUND: Macrophage activation by cytokines provides only a partial explanation of antimycobacterial immunity in man. Because cytolytic T lymphocytes have been shown to contribute to immunity in animal models of intracellular infection, the generation of mycobacterial antigen specific cytotoxic T cells was examined in the peripheral blood of patients with tuberculosis. METHODS: Subjects comprised 36 patients with active tuberculosis (18 newly diagnosed) and 32 healthy volunteers, of whom 25 had had BCG vaccination and seven were Mantoux negative. The ability of purified protein derivative (PPD) stimulated peripheral blood lymphocytes to lyse autologous, mycobacterial antigen bearing macrophages was examined by using a chromium 51 release assay. RESULTS: PPD stimulated lymphocytes from normal, Mantoux positive, BCG vaccinated subjects produced high levels of PPD specific cytolysis, whereas lymphocytes from unvaccinated, uninfected subjects caused little or no cytolysis. The generation of cytolytic T lymphocytes by patients with tuberculosis was related to their clinical state. Those with cavitating pulmonary disease or lymph node tuberculosis generated PPD specific lymphocytes with cytotoxic ability similar to that of those from Mantoux positive control subjects, whereas lymphocytes from patients with non-cavitating pulmonary infiltrates showed poor antigen specific cytolysis. After seven days of stimulation with PPD in vitro, lymphoblasts contained both CD4+ and CD8+ cells. Mycobacterial antigen specific cytolysis was restricted to the CD4+ cell population and was blocked by monoclonal antibodies directed against major histocompatibility class II (MHC) antigens. CONCLUSION: CD4+ cytolytic T cells can lyse autologous macrophages presenting mycobacterial antigen and were found in patients with cavitating pulmonary tuberculosis or tuberculous lymphadenitis and in normal, Mantoux positive control subjects. The ability to generate these T cell responses seems to be a marker for response to mycobacteria and may contribute to tissue damage in tuberculosis. These responses do not provide protective immunity against Mycobacterium tuberculosis but may help in disease localisation.

BCG Vaccine

Competition for hydrogen by human faecal bacteria: evidence for the predominance of methane producing bacteria.

Studies of sludge have shown that some species of sulphate reducing bacteria outcompete methane producing bacteria for the common substrate H2. A similar competition may exist in human faeces where the methane (CH4) producing status of an individual depends on the faecal concentration of sulphate reducing bacteria. To determine if non-methanogenic faeces outcompete CH4 producing faeces for H2, aliquots of each type of faeces were incubated alone or mixed together, with or without addition of 10% H2 and/or 20 mmol/l sulphate. Methane producing faeces consumed H2 significantly more rapidly and reduced faecal H2 tension to a lower value compared with non-methanogenic faeces. The mixture of the two types of faeces yielded significantly more CH4 than CH4 producing faeces alone (mean (SD) 8.5 (1.3) v 2.9 (0.45) mmol/l of homogenate per 24 hours, p less than 0.01). Faecal sulphide concentrations were similar in CH4 producing and non-producing homogenates both before and after 24 hours of incubation. The addition of sulphate to the homogenates did not significantly influence CH4 production or sulphide formation. Our results suggest that in human faeces methane producing bacteria outcompete other H2 consuming bacteria for H2.

Bacteria, Anaerobic

Specific lysis of mycobacterial antigen-bearing macrophages by class II MHC-restricted polyclonal T cell lines in healthy donors or patients with tuberculosis.

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.

Adult

A comparison of the effects of controlled-release levodopa (Madopar CR) with conventional levodopa in late Parkinson's disease.

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.

Adult

Myoglobinuria: the importance of reaching a firm diagnosis--a patient with defective fatty acid oxidation.

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.

Acute Kidney Injury

Review article: antibiotics and the gut.

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.

Animals

New vaccines.

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.

Humans