Biomedical subjects
S H Cheeseman
Publications and source records attributed to S H Cheeseman.
Hemophiliac immunodeficiency: influence of exposure to factor VIII concentrate, LAV/HTLV-III, and herpesviruses.
The relationship between hemophiliac immunodeficiency and exposures to factor VIII concentrate, LAV/HTLV-III retrovirus, and infection with Epstein-Barr virus and cytomegalovirus was examined. Exposure to factor VIII concentrate was significantly correlated with decreased percentages of T helper/inducer cells, decreased T helper/suppressor cell ratios, and decreased proliferative responses to plant mitogens. LAV/HTLV-III seropositivity was the primary predictor of increased percentages of HLA-DR-bearing mononuclear cells and decreased proliferative responses to pokeweed mitogen. Epstein-Barr virus and cytomegalovirus infections acted in a synergistic manner with LAV/HTLV-III to produce immunoregulatory defects. Increased percentages of T suppressor cells and decreased delayed cutaneous hypersensitivity skin test responses were observed in LAV/HTLV-III seropositive hemophiliacs infected with Epstein-Barr or cytomegalovirus. We conclude that hemophiliacs receiving commercial factor VIII concentrate experience several stepwise incremental insults to the immune system: alloantigens in factor VIII concentrate, LAV/HTLV-III infections, and herpesvirus infections.
Evaluation of a commercially available direct immunofluorescent staining reagent for the detection of respiratory syncytial virus in respiratory secretions.
A commercially-available direct immunofluorescence (IF) reagent (Imagen; Boots-Celltech, Slough, Berkshire, United Kingdom) was similar in sensitivity and specificity to the conventional indirect IF test for the detection of respiratory syncytial virus in respiratory secretions. Both IF tests were more sensitive than culture, particularly for specimens transported from outside the institution.
Cytomegaloviral infection and disease.
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Virologic studies in a case of transfusion-associated AIDS.
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Analysis of cytomegalovirus and Epstein-Barr virus antibody responses in treated hemophiliacs. Implications for the study of acquired immune deficiency syndrome.
One hundred hemophiliacs were studied for serological evidence of infection with cytomegalovirus (CMV), Epstein-Barr virus (EBV), and hepatitis B virus. Ninety-eight percent had markers of hepatitis B infection, while 69% had antibody to EBV and only 42% had antibody to CMV, suggesting that factor VIII preparations do not transmit EBV and CMV efficiently. Seventy-one percent of those seropositive to EBV had an antibody pattern suggestive of active infection, as compared with 23% of healthy young adult blood donors. These findings make the patients with hemophilia an unusually favorable population for the study of the role of persistent viral infection in the immunodeficiency now found to be widespread in groups at high risk for acquired immune deficiency syndrome (AIDS) and for the contribution of CMV and EBV to AIDS itself.
Late-onset group B streptococcal disease after peripartum ampicillin prophylaxis.
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Detection of cytomegalovirus antibody with two commercially available assays, an indirect hemagglutination test and an enzyme immunosorbent assay.
By the use of two reference procedures, an indirect hemagglutination assay and a complement fixation test, the presence or absence of cytomegalovirus (CMV) antibody was determined for 221 human sera. Ninety-nine sera (44.8%) were found to contain CMV antibody. The remaining 122 sera (55.2%) lacked detectable CMV antibody. These same sera were then analyzed by two recently introduced, commercially available CMV antibody assays, an indirect hemagglutination test (IHA-c; Cetus Corp., Emeryville, Calif.) and an enzyme-linked immunosorbent assay (ELISA; M. A. Bioproducts, Walkersville, Md.). With the results of the reference procedures as true evidence of the presence or absence of CMV antibody, the sensitivity of the IHA-c was found to be 100%; the specificity was 98.4%. The sensitivity of the ELISA was also 100%; the specificity was 96.7%. The overall accuracies of these procedures were 99.1 and 98.2%, respectively. Time and motion studies revealed the IHA-c procedure to be faster and technically less demanding than the ELISA procedure.
Studies on cytomegalovirus in human milk.
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Glomerulopathy associated with cytomegalovirus viremia in renal allografts.
We investigated the relation between cytomegalovirus (CMV) infection and renal-allograft dysfunction in 14 patients. In seven instances (including two successive transplants in one patient), allograft dysfunction occurred during clinically manifest, viremic CMV infection. In five of these, biopsies revealed little or no tubulointerstitial change but a distinctive, diffuse glomerulopathy characterized by enlargement or necrosis of endothelial cells and accumulation of mononuclear cells and fibrillar material in glomerular capillaries. Two of these allografts recovered their function, both with cessation of high-dose immunosuppression. Biopsies in the other 10 patients revealed predominantly tubulointerstitial changes typical of cellular rejection, and most of these patients did not have viremia. One additional patient, studied prospectively, manifested both forms of allograft injury: tubulointerstitial changes occurring two weeks after transplantation and responding to increased immunosuppression, and CMV-associated glomerulopathy occurring seven weeks after transplantation and responding to decreased immunosuppression. We conclude that viremic CMV infection can cause acute glomerular injury and that recovery may be favored by a decreased in immunosuppressants.
Kawasaki syndrome: description of two outbreaks in the United States.
Investigation of two outbreaks of Kawasaki syndrome (KS) in the United States in 1979 and in 1980 revealed no evidence of person-to-person transmission or of a common-source exposure among patients. Questionnaire data showed that KS was more likely to occur in children of middle and upper socioeconomic status than in those of lower status (P less than 0.05 and P less than 0.001 for the respective outbreaks) and that patients with KS had a higher incidence of an antecedent, primarily respiratory illness than did controls matched for age, sex, and race (83% of patients in the first outbreak vs. 30% of one control group, P less than 0.01, and vs. 36% of another control group, P less than 0.02; and 56% of patients in the second outbreak vs. 32% of their controls, P less than 0.02). However, laboratory studies did not identify an etiologic agent for either KS or for the antecedent illness that may be a risk factor for KS.
Pseudomonas denitrificans meningitis.
An elderly male patient with Pseudomonas denitrificans bacteremia and meningitis is described. The antimicrobial susceptibility and minimum criteria necessary for the identification of this unusual and rare human pathogen are discussed.
Interferon and BK Papovavirus--clinical and laboratory studies.
The effects of human leukocyte interferon on BK papovavirus (BKV) infection in 41 recipients of renal transplants were studied as part of a randomized, double-blind, placebo-controlled trial. Eight transplant recipients demonstrated fourfold or greater rises in antibody to BKV, and three excreted BKV in urine. Neither seroconversion nor excretion was reduced by interferon administration. No clinical syndromes could be clearly linked to BKV infection. BKV was also relatively resistant to the in vitro effects of interferon. Pretreatment of interferon-sensitive human fibroblasts with up to 620 units of interferon/ml resulted in a loss of viral infectivity of one log or less. Continuous exposure of infected cultures to these interferon levels reduced BKV titers by 1.5-2.9 logs, whereas continuous exposure to lower concentrations of interferon had less effects. The levels shown to be marginally effective in vitro were considerably higher than those achieved in these patients' sera.
Epstein-Barr virus infection in renal transplant recipients. Effects of antithymocyte globulin and interferon.
We studied Epstein-Barr (EB) virus excretion and antibody in 41 renal transplant recipients enrolled in a placebo-controlled trial of human leukocyte interferon. Half the patients were also treated with antithymocyte globulin. Epstein-Barr virus excretion occurred more often in recipients of cadaver kidneys (P = 0.03) and those receiving antithymocyte globulin (P = 0.04) and less often in patients given interferon (P = 0.08). Antibody to viral capsid antigen increased fourfold or more in 12 of 22 patients treated with antithymocyte globulin and in none of the non-antithymocyte globulin-treated group (P = 0.0002). Antibody to the restricted component of early antigen rose fourfold or more in eight patients and appeared related to the occurrence of syndromes similar to those attributed to cytomegalovirus in transplant recipients. We conclude that increasing immunosuppression augments the rate of EB virus reactivation and that EB virus may be an important pathogen in heretofore ill-defined syndromes.
Controlled clinical trial of prophylactic human-leukocyte interferon in renal transplantation. Effects on cytomegalovirus and herpes simplex virus infections.
A double-blind, placebo-controlled trial of interferon prophylaxis against viral infections was conducted in renal-transplant recipients receiving standard immunosuprressive therapy with or without antithymocyte globulin. Interferon was administered for six weeks, beginning on the day of transplantation. Cytomegalovirus excretion began earlier and viremia was more frequent in placebo-treated than in interferon-treated patients. Cytomegalovirus viremia correlated with clinical syndromes was more frequent in recipients of antithymocyte globulin. In contrast, neither interferon nor antithymocyte globulin altered excretion of herpes simplex virus. Reversible leukopenia and thrombocytopenia occurred in seven interferon recipients. Patient and graft survival were comparable in interferon and placebo groups. There preliminary results suggest that a six-week course of prophylactic interferon delays shedding of cytomegalovirus and decreases the incidence of viremia after transplantation. In contrast, antithymocyte globulin appears to increase the severity of infection from cytomegalovirus among these patients.
Cytomegalovirus excretion 2-14 years after renal transplantation.
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Fatal neonatal pneumonia caused by Echovirus type 9.
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Use of interferon in cytomegalovirus infections in man.
Human CMV is relatively sensitive to the antiviral effects of interferon in vitro. No controlled studies of interferon in human CMV infections have been reported. On the basis of case reports published to date, its usefulness in CMV infections of newborns or transplant recipients is unclear. Double-blind, placebo-controlled studies of interferon prophylaxis against CMV infections in renal transplant recipients are currently underway.