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Biomedical subjects

R E Warren

Publications and source records attributed to R E Warren.

At least 19 recordsLinked to original sources

Antibodies to meningococcal class 1 outer membrane proteins in South African complement-deficient and complement-sufficient subjects.

Inhibition assays were used to investigate human serum antibodies to the meningococcal class 1 outer membrane proteins. We adapted the whole-cell enzyme-linked immunosorbent assay technique to determine the ability of sera to inhibit the binding of murine subtyping monoclonal antibodies. Serum samples from 33 South African subjects with a deficiency in the sixth component of complement as well as serum samples from various groups of complement-sufficient subjects were investigated. Subjects were subdivided according to whether they were (i) convalescent from Neisseria meningitidis infections, (ii) nonconvalescent, or (iii) controls. Preliminary subtyping investigations had shown that P1.2 was present on 36% of meningococcal clinical isolates from Cape Province, South Africa. Assays with the anti-P1.2 antibodies showed the presence of high antibody levels in many deficient sera and moderately elevated levels in some sera from the complement-sufficient convalescent patients. P1.2, P1.4, P1.15, and P1.16 are epitopes situated on loop 4 of the class 1 outer membrane proteins, whereas P1.7 is on loop 1. Inhibition assays showed that human sera that inhibited binding by P1.2 monoclonal antibodies tended to inhibit the other monoclonal antibodies directed to loop 4 epitopes. This suggests that the epitopes recognized by the human antibodies are not exactly the same as the epitopes recognized by the murine monoclonal antibodies and raises the possibility of the importance of other epitopes.

Antibodies, Bacterial

Protecting neutropenic patients from bowel-derived organisms.

Prevention of infection from bowel-derived organisms in neutropenic patients requires both the appropriate use of chemoprophylaxis and close attention to the prevention of cross-colonization or cross-infection with resistant Enterobacteriaceae and pseudomonads. Control of common-source infection and control of Gram-positive infection are also important. The objectives of chemoprophylaxis should be considered and their efficacy regularly assessed. Non-absorbable antibiotics may have an important place in minimizing selection of resistant strains, but absorbed agents such as cotrimoxazole (trimethoprim/sulphamethoxazole) and 4-quinolones offer advantages over these and nalidixic acid as prophylactic agents. Ciprofloxacin prophylaxis is probably more effective at reducing Gram-negative bacteraemia than co-trimoxazole but overall mortality may be higher. Further confirmation and investigation of the reasons for this are needed. Protocols of rational antibiotic prophylaxis and treatment involving these agents can be modified to cover only the Gram-negative superinfections that are likely.

4-Quinolones

An assessment of the Kemble Star 700 sample processor for the automation of complement fixation and ELISA tests in a microbiology laboratory.

A Kemble Robotic sample processor was programmed to perform routine serological tests for microbiology. Accuracy of dispensed volumes was assessed and precision of dilutions was compared with manual methods. An appraisal of time taken to perform complement-fixation and enzyme-linked immunosorbent assays by manual and automated methods was undertaken. Labour requirements were reduced when processing large numbers of samples and the reproducibility of more demanding tests was improved by the greater accuracy of the robotic manipulations.

Automation

An assessment of the efficacy of antimicrobial prophylaxis in bone marrow autografts.

Fifty-three patients undergoing autologous bone marrow transplantation received antimicrobial prophylaxis with ciprofloxacin with or without erythromycin and low dose intravenous amphotericin B. Eight patients remained afebrile throughout the neutropenic period. All other patients had one or more febrile episodes. The median time to fever after the onset of neutropenia was 7 days. There were no gram-negative organisms isolated from blood cultures during any of these episodes whereas gram-positive organisms were isolated in 28. There was one death in this series associated with sepsis. The use of low-dose prophylactic parenteral amphotericin did not prevent the subsequent successful use of full dose amphotericin for antibiotic-resistant fever. Ciprofloxacin effectively prevents gram-negative sepsis. The addition of erythromycin does little to prevent gram-positive sepsis. The use of regimens with agents with activity against gram-positive organisms is appropriate initial treatment of all febrile neutropenic episodes.

Adolescent

Prevention of infection by ciprofloxacin in neutropenia.

Ciprofloxacin with erythromycin, each at a dose of 250 mg 12-hourly, is effective prophylaxis against Gram-negative bacteraemia in neutropenic patients. The erythromycin component may contribute little to prophylaxis and does select for erythromycin-resistant viridans streptococci which then cause bacteraemia. Ciprofloxacin prophylaxis does not prevent coagulase-negative staphylococcal bacteraemia and resistant strains are selected. Initial use of vancomycin with a ureidopenicillin in pyrexial patients is currently justified by the exclusively Gram-positive nature of breakthrough bacteraemia. In patients failing to respond to this regimen, treatment modification to include full-dose amphotericin is frequently effective. Surveillance and containment isolation of patients carrying resistant Gram-negative species is prudent to prevent the spread of such resistant bacteria in oncology/haematology units.

Ciprofloxacin

Effect of sample volume on yield of positive blood cultures from adult patients with haematological malignancy.

Six hundred and sixteen blood samples from patients with haematological malignancy were each distributed equally among three identical cells in a Malthus Microbiological Growth Analyser. The mean (SD) volumes inoculated into sets in which one, two, or three of the three bottles were positive were 37.7 (10.1) ml, 37.4 (12.9) ml, and 37.7 (10.5) ml, respectively. Overall, clinically important organisms were isolated from one bottle only with 18 cultures, from two bottles only with 19 cultures, and from all three bottles in a set with 104 cultures. If the yield from a single bottle inoculated with a mean volume of 12.6 ml blood is taken as 100%, the yield from 25.2 ml in two bottles was 110.7% and the yield from 37.7 ml in three bottles was 115.6%. The increased yield from increased volume was considerably lower than that reported from unselected groups of patients, which suggests that the magnitude of bacteriaemia is greater in patients with neutropenia. The isolation of infecting organisms from the blood of patients with neutropenia is, however, particularly important in directing chemotherapy and consequently 45 ml blood samples from these patients continue to be requested.

Adult

Shigella colitis with radiological and endoscopic correlation: case report.

We report a patient with acute colitis secondary to Shigella flexneri infection. Radiologic and endoscopic studies were obtained during and after the patient's clinical recovery. Hypotonic air contrast barium enemas were helpful in evaluating the severity and extent of the disease proximal to the segment viewed by flexible sigmoidoscopy. They showed pseudopolyposis, which has not been previously reported in the acute phase, and other mucosal abnormalities which persisted long after clinical recovery.

Colitis

Fat embolism in acute pancreatitis.

A patient who developed progressive hypoxemia and multiple system failure during the course of acute pancreatitis is described. Autopsy showed fat emboli to the lungs, kidneys, and heart, as well as multiple petechial hemorrhages in the brain. We conclude that fat embolism should be considered in the differential diagnosis of progressive hypoxemia in patients with acute pancreatitis.

Acute Disease

Difficult streptococci.

Streptococci pose difficulties in laboratory and clinical diagnosis and in therapy. They are important pathogens with both potential for high mortality in acute infections and endocarditis, and recurrence and persistence in foreign-body associated infections. Prevention of serious infection and spread of infection pose a number of hospital problems but hospital difficulties may originate in community wide outbreaks which also require investigation and control. Our experience with septicaemia caused by Lancefield Group A streptococci, and with Group D streptococcal bacteraemia in liver transplant recipients are reported and both national and international problems with antibiotic resistant streptococci are reviewed.

Adolescent

First recognized community outbreak of haemorrhagic colitis due to verotoxin-producing Escherichia coli O 157.H7 in the UK.

The first recognized outbreak of haemorrhagic colitis due to Escherichia coli O 157.H7 in the United Kingdom affected at least 24 persons living in East Anglia over a 2-week period. The illnesses were characterized by severe abdominal pain and bloody diarrhoea of short duration. Eleven patients were admitted to hospital and there was one death. Patients were mainly adult women who had not eaten out of the home in the 2 weeks before onset. Unlike previously reported outbreaks hamburgers were not the vehicle of infection, and a case-control study suggested that handling vegetables, and particularly potatoes, was the important risk factor.

Adult

Clostridium tertium septicemia in patients with neutropenia.

Eighteen adult patients with hematologic malignancy developed bacteremia due to Clostridium tertium while neutropenic. Fifteen had accompanying abdominal pain, colonic bleeding, or diarrhea, and three had perianal cellulitis. Fourteen recovered with antibiotic therapy alone; no patient was treated by surgery. C. tertium is an unusual Clostridium because it is resistant to many beta-lactam antibiotics and to metronidazole but is susceptible to vancomycin, trimethoprim-sulfamethoxazole, and ciprofloxacin. It is possible that use of third-generation cephalosporins (cefotaxime, ceftizoxime, ceftazidime) for treating febrile episodes in the absence of any selective intestinal decontamination with trimethoprim-sulfamethoxazole or ciprofloxacin may have resulted in selection for C. tertium in our patients.

Adolescent

Prospective addition of beta-lactamase to blood culture medium.

The value of adding beta-lactamase to bottles of blood-culture medium before their distribution to wards was investigated. Significantly more bottles containing beta-lactamase were culture-positive than those without (p less than 0.002). In another series, when the enzyme was added to both bottles in each set there was no significant difference in isolation rates between the two bottles. The groups of organisms which were isolated more readily when beta-lactamase was present were staphylococci and streptococci. Storage of beta-lactamase (Genzyme broad-spectrum mixture) in blood-culture medium at room temperature resulted in rapid loss of cephalosporinase activity, whereas little decline in penicillinase activity was noted over a period of 118 days.

Anti-Bacterial Agents

Haemorrhagic colitis: detection of verotoxin producing Escherichia coli O157 in a clinical microbiology laboratory.

Faeces (n = 1319) were examined over three months for the presence of non-sorbitol fermenting, verotoxin producing Escherichia coli (serotype O157). Seven isolates were found, four from patients with bloodstained diarrhoea and three from patients with no evidence of blood in the faeces. Screening of all faecal samples with specific O157 antiserum for non-sorbitol fermenting organisms and agglutination was an important adjunct to clinical and microscopic findings and helped detect cases of verotoxin producing E coli which might otherwise have been missed.

Bacterial Toxins

Automated screening of blood cultures with the Malthus microbiological growth analyser.

A total of 3347 blood cultures from patients in all hospital wards were examined on a Malthus microbiological growth analyser and by a conventional system. There was no significant difference in the total numbers of positive cultures of clinical importance between the two systems (p greater than 0.05). Staphylococcus aureus, however, was isolated more often by the conventional method (p less than 0.05). Failure of the automatic detection routine limited the potential of the Malthus system for earlier detection of positive cultures. Daily visual examination of Malthus curves and subculture of bottles not promptly attached to the apparatus were necessary to avoid missing some positive cultures. False positive rates were 13% for the Malthus system and 2% for the conventional system. The contamination rate was considerably lower in the Malthus system (p less than 0.001). Further development would be necessary for the apparatus to be acceptable for routine screening of blood cultures.

Bacteria

Streptococcus pyogenes bacteraemia in Cambridge--a review of 67 episodes.

Sixty-seven episodes of bacteraemia due to Lancefield Group A streptococci occurred in patients admitted to or autopsied at Addenbrooke's Hospital, Cambridge from July 1974 to June 1986. Ninety-two per cent of infections were acquired in the community and 71 per cent of patients were adults. The overall mortality rate was 48 per cent and 15 per cent of cases died at home shortly after the onset of illness. Thirty-eight per cent of the patients had underlying disease and sixty-one per cent of these died compared with 40 per cent of those without underlying disease. Presentation in shock was the major predictor of mortality (79 versus 16 per cent) and was commoner in adults. Clinical features were variable and led to incorrect initial diagnosis in some cases. A localized site of infection was not recognized initially in 37 per cent of cases but the commonest evident site of entry was the skin. Annual incidence varied with age from 0.71 to 4.16/100,000 population and cases were commonest in the young and those over 50. The fulminating onset of community-acquired streptococcal infection in some adults emphasizes the importance of early treatment of suspected cases with penicillins.

Adolescent

Bacteriology and antibiotic treatment of perineal suppurative hidradenitis.

A plausible bacterial pathogen (Streptococcus milleri, Staphylococcus aureus, anaerobic streptococcus, or Bacteroides species) was isolated at least once in 26 of 32 patients with active perineal suppurative hidradenitis. The main pathogen was S milleri, whose presence was significantly associated with disease activity and whose disappearance significantly correlated with clinical improvement; S aureus nd anaerobic streptococci were also implicated.

Adult