Biomedical subjects
Publications and source records attributed to T R Rogers.
Rhizopus oryzae was the causative organism in a fatal case of rhinocerebral and then pulmonary mucormycosis in a patient cured of her underlying leukaemia by bone marrow transplantation. We discuss the risk factors involved and the need for maintaining a high index of suspicion of fungal infection in the late post-transplant period.
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Virus infections account for considerable morbidity in bone marrow transplant (BMT) recipients. In all ages, members of the herpes virus group are the predominant pathogens. Of these, cytomegalovirus is pre-eminent in being the most frequent cause of death due to infection associated with the transplant procedure. Considerable effort is being invested in the development of preventative and therapeutic strategies to control this virus. Other potentially life-threatening virus infections may be acquired on the transplant unit as a result of cross-infection and can be caused by enteroviruses, rotaviruses and adenoviruses. Prevention of these infections is best achieved by implementation of strict infection-control measures.
A 12-year-old boy in third remission acute lymphoblastic leukaemia was given a mismatched transplant from his mother. He suffered prolonged neutropenia and pyrexia which was only finally diagnosed as toxoplasmosis using molecular biology methods and by his response to appropriate treatment. This was probably transmitted by bone marrow transplant since maternal immune T cells were removed by the use of Campath-1G and treatment with cyclosporin A probably prevented his IgM immune response and impeded the diagnosis.
The polyenes, amphotericin B and mepartricin and the imidazoles, miconazole, ketoconazole, itraconazole and fluconazole, were studied either alone or in paired polyene-imidazole combinations to determine their activity in vitro against clinical yeast isolates. The methods included shaken and standing liquid cultures, continuous cultures and chequerboard titrations, with or without the incorporation of pooled human plasma. The polyenes were found to exert an immediate cidal action even with high cell populations whereas the imidazoles demonstrated a time-dependent fungistatic activity which increased very slowly with increase in drug concentration. The interactions observed with the paired combinations were consistent and were found to be anomalous with all methods used. The activity of the imidazoles was enhanced by the presence of the polyenes; by contrast the polyenes were strongly antagonized by the imidazoles.
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Two ELISAs were used to detect serum and urinary aspergillus antigen in 121 patients who were profoundly neutropenic after leukaemia therapy or bone marrow transplantation. The presence of antigen correctly predicted development of invasive pulmonary aspergillosis (IPA) in 16 patients. In 2 other cases antigen appeared after the clinical diagnosis had been made, while in only 1 case was antigen not detected. In 11 of 13 episodes of clinically suspected fungal infection antigen was detected before clinical diagnosis was made. By contrast, antigen was detected in only 1 of 90 patients who had no evidence of IPA. Both ELISAs gave positive and negative predictive values for IPA of greater than 95%, demonstrating the value of antigen detection in early diagnosis of aspergillus infection and the assay's ability to predict subsequent development of IPA. We conclude that neutropenic patients should be screened for aspergillus antigen, and propose that initial detection of fungal antigen justifies commencement of empirical antifungal therapy. Such an approach should improve the survival of patients who are at risk of developing this usually fatal infection.
Ten satisfied and ten dissatisfied married couples described how they make decisions of low, moderate, and high levels of difficulty. Responses were coded as reflecting the use of equity, need-based, situational, or other norms. Results were consistent with previous findings that a state of equity is associated with marital satisfaction but also indicated that multiple norms are used in decision making of both satisfied and dissatisfied couples. Decision difficulty influenced use of both situational and need-based norms. A trend was found for satisfied husbands but not wives, to make greater use of need-based norms than dissatisfied husbands when decisions were high in difficulty. The results are interpreted as supporting a distinction between equity as a state and equity as a process and as supporting an instrumental value theory of norm use.
Serial urine samples were collected from 33 neutropenic patients, 10 of whom developed invasive aspergillosis (IA) while undergoing bone marrow transplantation or remission induction therapy for leukemia. Concentrated urine samples from the infected patients were subjected to polyacrylamide gel electrophoresis, blotted, and then incubated with antiserum raised to a cell wall extract of Aspergillus fumigatus (anti-CW) or an immunoglobulin G monoclonal antibody to A. fumigatus galactomannan (EBA1). When IA patient urine blots were probed with anti-CW, major bands at 11 and 18 kilodaltons (kDa); intermediate bands at 13, 14, and 29 kDa; and minor bands at 38 and 44 kDa were seen. In contrast, EBA1 showed diffuse staining at molecular masses larger than 45 kDa and a single weak band at 21 kDa. Urine samples from the 23 patients with no evidence of IA were unreactive with both anti-CW and EBA1. These antigen bands are likely to represent immunodominant antigens which are excreted during IA and should play a valuable role in the development of rapid diagnostic tests for aspergillosis.
In the course of construction of a new bone marrow transplantation (BMT) unit, six of nineteen children undergoing BMT in the adjacent ward area died of invasive pulmonary aspergillosis (IPA). Ward air samples confirmed that heavy fungal spore contamination had occurred. The introduction of laminar air flow (LAF) isolation terminated the outbreak and no subsequent cases of IPA have been documented in patients nursed entirely in LAF. LAF has not reduced the rates of other complications associated with BMT.
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A randomized comparative study was conducted to evaluate the clinical efficacy of amoxycillin/clavulanate (Augmentin) compared with mezlocillin for the prevention of wound infection in patients undergoing abdominal surgery. There was no difference in overall wound infection rates between the amoxycillin/clavulanate treated group and the mezlocillin group. When sub-groups were examined for total infections no significant difference was seen between antibiotic groups in patients undergoing clean/potentially contaminated operations or contaminated operations, although more deep infections were encountered in the amoxycillin/clavulanate group in comparison with the mezlocillin group, in contaminated operations. The type of operation performed also failed to show any difference in those patients undergoing upper gastro-intestinal, appendiceal, colonic, or biliary operations. The infections in those receiving amoxycillin/clavulanate were largely of bowel origin and predominantly sensitive to amoxycillin/clavulanate. Those in the mezlocillin group were predominantly staphylococcal in origin. Amoxycillin/clavulanate appears to be an effective antibiotic for use as a single agent in surgical prophylaxis.
Eight of 22 non-capsulate strains of Neisseria meningitidis previously isolated from primary school children were re-identified as N. polysaccharea by aminopeptidase reactions and polysaccharide production. N. polysaccharea was not identified amongst 91 non-capsulate strains of N. meningitidis isolated from adults attending the Genito-urinary Medicine clinic, Westminster Hospital, London. The biochemical reactions of N. polysaccharea strains were similar to those of N. lactamica and N. gonorrhoeae, but N. polysaccharea could be distinguished from these organisms by examination of beta-galactosidase activity, carbohydrate reactions and polysaccharide production. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed closer similarity of N. polysaccharea to N. lactamica than to the pathogenic Neisseria spp. An additional finding was variation in the position of one of the major proteins of N. lactamica in the 34-39-Kda region.
Sera from 29 children and six adults were used to investigate the nature of antigenic cross-reactivity between Neisseria polysaccharea, N. lactamica and N. meningitidis B,15P1.16 by immunoblotting. Major common antigens of 68-70 Kda, 60-65 Kda and 15-20 Kda were detected. Antibody directed against them uniformly decreased after absorption of the sera with the three different Neisseria species. Antigens of 55 Kda and 35 Kda specific to N. meningitidis, and one of 43 Kda specific to N. lactamica, were also demonstrated. Antibody against all antigens was more prevalent in bactericidal than in non-bactericidal sera, although these differences were statistically not significant. Differences in antibody prevalence between carriers of Neisseria spp. and non-carriers of these organisms were even less marked. Examination of sera by whole-cell enzyme-linked immunosorbent assay against N. meningitidis B,15P1.16 and N. lactamica gave an absorbance ratio of 1:1. Only four sera from children showed no reactivity against the meningococcal strain. These common antigens are likely to be important in vaccine development.
A randomized controlled trial was undertaken to compare the role of mezlocillin, as the sole prophylactic agent, with a combination of cefuroxime and metronidazole in patients undergoing biliary and gastrointestinal surgery. No difference in wound infection rates was seen in patients following appendicectomy, biliary or gastro-oesophageal surgery. A significantly higher wound infection rate was seen in patients undergoing colorectal surgery who received mezlocillin alone (30.2%) compared with those receiving cefuroxime and metronidazole (11.5%): this rate was similar to that of historical placebo controls in other units. The wound infections seen in patients receiving mezlocillin alone were polymicrobial involving organisms of faecal origin, including non-sporing anaerobes which were predominantly sensitive to mezlocillin. Infections due to Staphylococcus aureus, resistant to mezlocillin, were more frequent in patients receiving mezlocillin and usually secondary in nature. We conclude that mezlocillin may be an effective sole prophylactic agent in appendicectomy but not in colorectal surgery; the possible reasons for failure to adequately prevent infection, following colorectal surgery, are discussed.