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Biomedical subjects

D Pillay

Publications and source records attributed to D Pillay.

At least 109 records · Page 6Linked to original sources
PubMed1993

Cytomegalovirus infection and risk of AIDS in human immunodeficiency virus-infected hemophilia patients. National Cancer Institute Multicenter Hemophilia Cohort Study Group.

The effects of prevalent and incident cytomegalovirus (CMV) infection on human immunodeficiency virus (HIV) disease progression were examined in 393 hemophilia patients with known dates of HIV seroconversion. Of the cases, 191 (49%) had IgG antibody to CMV in their earliest stored sera (median date, November 1983). CMV-seropositive subjects were one and a half times more likely to develop AIDS, and they were also older than CMV-negative subjects. Adjusted for age, CMV seropositivity was not associated with the development of AIDS. In age-adjusted analyses, CMV-seropositive subjects had a small, but statistically insignificant, decrease in survival after HIV seroconversion. Older subjects were more likely to CMV seroconvert by the time of their latest available serum samples (P = .03). CMV seroconverters were five times more likely to develop clinical CMV disease than were subjects initially CMV-positive (P = .02). To avoid this source of serious morbidity, CMV-seronegative hemophiliacs with HIV infection should not be exposed to cellular blood products or body fluids from CMV-seropositive donors.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A clinico-pathological audit of opportunistic viral infections in HIV-infected patients.

OBJECTIVE: To determine the prevalence of opportunistic viral infections in multiple tissues at postmortems of HIV-infected patients, and to relate these findings to their antemortem clinical course. DESIGN: A study of viral infections in 16 tissues of HIV-positive postmortem cases, by a combination of histology and cell culture (virus isolation). Clinical details were abstracted retrospectively from patient records. PATIENTS: Forty-seven consecutive autopsies, performed between 1985 and 1992. SETTING: Autopsies were conducted by a single pathologist in a single London teaching hospital. RESULTS: Opportunistic viral infections were detected in 72% of all cases, comprising cytomegalovirus (CMV, 66%), herpes simplex virus (11%), JC virus (6%) and adenovirus (2%). The most commonly infected tissues were lung, adrenal, gastrointestinal tract and central nervous system, although all tissue sites sampled could potentially support viral replication. Of 464 tissues tested by both histology and cell culture, histology alone detected CMV in 45 tissues and cell culture alone detected CMV in 31 tissues. We determined that CMV detection in postmortem gastrointestinal tissues and central nervous tissue was significantly associated with antemortem undiagnosed diarrhoea and encephalitis, respectively. CONCLUSION: There is a high prevalence of opportunistic viral infections in late-stage HIV disease, which is best detected postmortem by the use of both histology and cell culture. Many of these infections correlate with undiagnosed symptoms antemortem. The ability of sensitive methods for virus detection to alert the clinician to such cases antemortem should be critically evaluated, as should attempts to influence the natural history of these infections by antiviral drugs. Continuing clinico-pathological audit is important for AIDS patients in order to monitor the impact of known opportunistic viral infections and to identify others which may emerge as immunosuppression becomes more profound.

AIDS-Related Opportunistic Infections↗
PubMed1993

The prognostic significance of positive CMV cultures during surveillance of renal transplant recipients.

Renal transplant recipients are at risk of severe morbidity and mortality from CMV disease. We have undertaken routine surveillance for CMV shedding on 133 transplant recipients, using a rapid culture technique, in order to assess the incidence of CMV infection and disease in these patients and to assess the prognostic significance of detection in whole blood, throat swab specimens, or urine. Donor CMV seropositivity was associated with posttransplant CMV infection (P < 0.05) and disease (P = 0.06). CMV infection and disease were associated with the receipt of anti-T-cell antibodies (P < 0.0001 and P = 0.08, respectively). First shedding of virus from any site occurred earlier posttransplant in those recipients who developed disease (median 39 days) than in those who did not (median 55 days)(P < 0.05). Detection of virus in blood occurred at a median time of 16 days before onset of symptoms, compared with 9 days before symptoms in urine, and 3 days after onset of symptoms from throat swab. A positive blood culture represented a relative risk of 7.1 for the subsequent development of disease, compared with 2.1 and 1.8 for positive urine and saliva cultures, respectively. The addition of urine cultures to blood cultures increased the sensitivity for identification of those at risk--however, the relative risk was reduced to 5.8. We conclude that routine surveillance for CMV shedding, especially in blood and urine, can identify recipients at high risk of CMV disease, and propose a trial in which those with asymptomatic viremia are allocated to receive ganciclovir or placebo, in order to assess the efficacy of "preemptive" therapy in this group of patients.

Antilymphocyte Serum↗
PubMed1993

Provision of prognostic information in immunocompromised patients by routine application of the polymerase chain reaction for cytomegalovirus.

A polymerase chain reaction (PCR) assay that amplifies a 149 base pair fragment of the cytomegalovirus glycoprotein B gene was used in the routine screening of 548 urine and 248 blood specimens from immunocompromised patients. The PCR results were compared with those obtained for the same specimens tested by the methods of conventional cell culture (CCC) and detection of CMV-specific immediate-early antigen fluorescent foci (DEAFF). For both urine and blood, PCR positivity correlated with a positive result in CCC (urine 93.2%; blood 86%). As expected for a more sensitive assay, PCR also identified CMV in samples that were negative by CCC and DEAFF such that there was no concordance between tests (Kappa test P > 0.05). The sensitivity, specificity, positive predictive value, and negative predictive values of PCR positivity in blood with respect to CMV disease were 0.8, 0.86, 0.62, and 0.94, respectively, with an associated relative risk of 5.84 (95% CI; 3.2-10.8). PCR detection of CMV in urine was more sensitive than either DEAFF or CCC (0.6 vs. 0.35 and 0.5, respectively) and had a high negative predictive value (0.89) but the positive predictive value was lower than either CCC or DEAFF (0.32 vs. 0.41 and 0.37, respectively) with respect to disease. Longitudinal data on patients with disease showed that CMV in blood was detected at a median of 5 days (range; -20 to +3 days) before disease onset whereas CMV was detected by CCC at a median of 13 days (range -4 to +20 days) after disease onset. In addition, the PCR assay was integrated into the battery of tests routinely performed on transplant patients in the diagnostic laboratory at this institution.

AIDS-Related Opportunistic Infections↗
PubMed1993

Characterization of a nested polymerase chain reaction assay for detection of parvovirus B19.

The characterization and application of a nested polymerase chain reaction (PCR) assay for the detection of human parvovirus B19 DNA is described. The assay was evaluated with 149 diagnostic serum samples (collected up to 150 days after the onset of symptoms) previously tested by dot blot hybridization for B19 DNA and by class-specific capture radioimmunoassays for the detection of B19 immunoglobulin M (IgM) and IgG. B19 DNA was detectable by the PCR in 70% of the sera. There was a statistically significant association between the detection of B19 DNA by PCR and high B19 IgM values (P < 0.005), low B19 IgG values (P < 0.05), and a short interval between onset of symptoms and serum collection (P < 0.005). Serial serum samples, throat swabs, and peripheral blood mononuclear cells collected from 10 individuals during an outbreak of parvovirus B19 were also tested by the nested PCR. B19 DNA was detectable in the throat swabs at the time of the clinical illness and in the peripheral blood mononuclear cell fraction up to the end point of the study 6 months after infection. The location of the B19 DNA could not be determined in cytocentrifuge preparations of peripheral blood mononuclear cells with nonisotopic in situ hybridization and immunolabelling.

Antibodies, Viral↗
PubMed1993

Audit of endoscopic surveillance biopsy specimens in HIV positive patients with gastrointestinal symptoms.

An audit of upper gastrointestinal endoscopy in HIV infected patients with gastrointestinal symptoms assessed the frequency of disease detected by endoscopy and routine laboratory analysis of surveillance biopsy specimens. Sixty nine consecutive endoscopies were performed in 59 HIV infected patients. Endoscopic biopsy specimens were taken from the lower oesophagus, gastric antrum, and third part of the duodenum for virology, histopathology, parasitology, bacteriology, and mycobacterial culture. Endoscopic appearances detected disease in 25/59 (42.4%) patients (oesophageal candida, 14; oesophageal ulcer, 3; Kaposi's sarcoma, 4; others, 4), but only 4/43 (9.3%) specimens showed evidence of disease in the absence of endoscopic abnormality. Virology for cytomegalovirus (detection of early antigenic fluorescent foci and culture) was positive in 6/59 (10.2%) patients, but parasitology and mycobacterial culture were negative in all cases. Histopathology was abnormal in 11/52 (21%) oesophageal biopsy specimens, 13/47 (28%) gastric biopsy specimens, and 4/65 (6%) duodenal biopsy specimens. Abnormal findings were found predominantly in those with advanced HIV disease (CDC Stage IV) (21/33 patients (64%)) compared with those with early HIV disease (CDC Stage II) (5/26 (19%)). In conclusion, upper gastrointestinal endoscopy detects macroscopic disease in AIDS patients and those with low CD4 counts, but routine surveillance biopsy specimens of apparently normal bowel in early HIV disease (or where CD4 counts are greater than 0.2 x 10(9)/1) are of little value.

Adolescent↗
PubMed1993

Value of routine surveillance cultures for detection of CMV pneumonitis following bone marrow transplantation.

The results of 5018 surveillance cultures for the detection of cytomegalovirus (CMV) from 177 patients undergoing allogeneic T cell-depleted bone marrow transplantation (BMT) were analysed to determine their value in predicting future development of CMV pneumonitis. Twenty-two patients were diagnosed as having CMV pneumonitis. The median times of a positive CMV culture result from urine, saliva or blood before disease in these patients were 32, 8 and 23 days, respectively. The positive predictive value of CMV viraemia for the development of CMV pneumonitis was 0.64. Multivariate analysis showed that recipient pretransplant CMV seropositivity and increasing recipient age were independent risk factors for CMV pneumonitis. By contrast, donor CMV seropositivity was protective against disease, supporting the hypothesis that immunity against CMV can be adopted from donor T cell-depleted marrow. It is concluded that detection of CMV viraemia in a surveillance protocol can predict subsequent CMV pneumonitis but that it is of low sensitivity. This might be improved by more frequent sampling or by the use of a more sensitive assay, such as the polymerase chain reaction, thus identifying individuals who may benefit from 'pre-emptive' therapy.

Antibodies, Viral↗
PubMed1992

Parvovirus B19 outbreak in a children's ward.

Parvovirus B19 infection can cause severe complications in pregnant women, individuals with haemolytic anaemia, and those who are immunocompromised. In a hospital outbreak of this infection, a balance should be struck between protection of these individuals and the maintenance of medical services. The index case of an outbreak of parvovirus B19 infection among staff and patients of a paediatric ward was not identified. 58 members of staff were screened for B19 markers and 4 of the 6 susceptible men and 6 of the 24 susceptible women became infected (p = 0.05) as defined by serum IgM and viraemia. 1 of the 11 adults (10 members of staff and 1 parent) infected remained symptom-free. 12 immunocompromised patients were also assessed, and symptom-free infection developed in 2 of these. During the outbreak staff with symptoms were put on sick leave, immunocompromised patients (there were none with haemolytic anaemia) were given normal human immunoglobulin and nursed in single rooms by B19 IgG-positive, IgM-negative staff, and the ward was closed to B19 IgG-negative pregnant women. However, the limitation of spread of infection cannot be attributed with certainty to the measures taken.

Adult↗
PubMed1992

Risk factors for viral reactivation following bone marrow transplantation.

The identification of risk factors for viral reactivation following transplantation is essential in order that antiviral prophylactic regimes may be allocated rationally. In the pretransplant period qualitative serological assessment of recipient and donor is informative with regard to the risk of post-transplant reactivation and disease. In addition, the quantitative level of herpes simplex virus (HSV) IgG in the pretransplant recipient is predictive of post-transplant HSV excretion, although this relationship does not exist for other viruses of the herpes group. We discuss the value of surveillance cultures for cytomegalovirus in the post-transplant period in predicting the development of CMV disease, and how this may allow effective intervention to prevent what is a major cause of morbidity and mortality in the transplant population.

Antibodies, Viral↗
PubMed1992

Detection of cytomegalovirus by a rapid culture system: a comparison of monoclonal antibodies in a clinical setting.

A monoclonal antibody cocktail, directed against immediate early antigens of cytomegalovirus, was assessed in a rapid culture system for detection of CMV (DEAFF) in clinical samples. The antibody cocktail was shown to be equivalent in sensitivity and specificity to our currently used monoclonal antibody. A comparison of DEAFF (using either monoclonal preparation) and conventional cell culture shows that DEAFF detects a smaller proportion of CMV positive samples from those receiving antiviral chemotherapy. The reasons for the discrepancies observed between these techniques are discussed.

Antibodies, Monoclonal↗
PubMed1992

Relationship between herpes simplex virus ulceration and CD4+ cell counts in patients with HIV infection.

OBJECTIVE: To establish the incidence of herpes simplex virus (HSV) ulceration in relation to CD4+ cell counts in HIV-infected patients. DESIGN: Swabs were taken from all ulcerated lesions in HIV-infected patients and cultured for HSV. CD4+ cell counts were performed at regular intervals. SETTING: The HIV unit at a London teaching hospital (the Royal Free Hospital, London, UK). PATIENTS: All HIV-infected patients (n = 500) attending the HIV unit. RESULTS: Two hundred and twenty-three swabs were obtained from 118 patients; 83 (37.2%) swabs from 62 (52.5%) patients were positive for HSV. Of 96 swabs taken from patients with CD4+ cell counts < 50 x 10(6)/l, 56 (58.3%) were positive for HSV, compared with 27 of 127 (21.2%) swabs from patients with higher CD4+ cell counts (P < 0.0001). Of patients with CD4+ cell counts < 50 x 10(6)/l, 37 of 47 (78.7%) had positive cultures compared with 25 of 71 (35.2%) of patients with higher counts (P < 0.0001). This trend was observed with swabs from all body sites; sufficient samples were available from oral and perianal lesions to demonstrate statistical significance (P < 0.0001 and P = 0.007, respectively). CONCLUSIONS: These results show a sharp rise in the incidence of HSV with CD4+ cell counts < 50 x 10(6)/l and thus provide important data for the design of studies of anti-HSV prophylaxis. Furthermore, since nearly 60% of all ulcers in patients with such low CD4+ counts are HSV-positive, we suggest appropriate empirical therapy on presentation.

AIDS-Related Opportunistic Infections↗
PubMed1992

Surveillance for CMV infection in orthotopic liver transplant recipients.

Infection with cytomegalovirus is a major cause of morbidity and mortality following orthotopic liver transplantation. In order that preventive strategies may be devised, a detailed assessment of risk factors for infection and disease is required. We have prospectively assessed 46 orthotopic liver transplant recipients for CMV excretion from multiple sites in order to determine incidence of, and risk factors for, CMV infection and disease. Risk factors for posttransplant CMV infection were donor CMV seropositivity, an increased volume of peritransplant whole-blood transfusion and an increased dose of extra steroid therapy to treat rejection episodes. These findings implicate, respectively, transfer of virus with donor organ, transfer of virus with blood transfusion, and stimulation of reactivation of latent virus in recipients through augmented immunosuppression. The possible ways of preventing or ameliorating these effects are discussed.

Adult↗
PubMed1992

JC virus associated meningoencephalitis in an immunocompetent girl.

JC virus is most commonly acquired during childhood, and no clinical illness has been associated with primary infection, which is assumed to be asymptomatic. The only disease associated with JC virus to date is progressive multifocal leucoencephalopathy (PML), which is usually caused by viral reactivation in immunocompromised adults. A chronic meningoencephalitis associated with an active JC virus infection in an immunocompetent 13 year old girl is described.

Adolescent↗
PubMed1991

Cytomegalovirus excretion after bone marrow transplantation cannot be predicted from the pre-transplant level of IgG antibodies.

The relationship of pre-bone-marrow transplant recipient and donor cytomegalovirus (CMV) antibody level to post-transplant recipient CMV excretion was investigated. CMV excretion was found to be related to pre-transplant recipient serological status, but not to level of antibody. This therefore contrasts with herpes simplex virus (HSV), for which pre-transplant antibody level in recipients predicts post-transplant HSV excretion.

Adolescent↗
PubMed1985

Effects of 2[5(4-chlorphenyl)pentyl]oxirane-2-carboxylate on fatty acid synthesis and fatty acid oxidation in isolated rat hepatocytes.

The effects of the hypoketonaemic and hypoglycaemic compound 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) on fatty acid synthesis and fatty acid oxidation in rat hepatocytes were examined. Two microM-POCA caused a small stimulation of fatty acid synthesis which might be due to an increased flux through pyruvate dehydrogenase. Ten to one hundred microM-POCA inhibited (40-70%) fatty acid synthesis. At low concentrations (less than or equal to 5 microM) POCA was a more powerful inhibitor of fatty acid oxidation than of synthesis, but at higher concentrations (10-100 microM) the inhibition of synthesis and oxidation was similar. One hundred microM POCA-CoA inhibited acetyl-CoA carboxylase by about 22% and 100 microM-palmitoyl-CoA by about 33%. Since POCA was a more potent inhibitor of fatty acid synthesis than palmitate, but POCA-CoA did not inhibit acetyl-CoA carboxylase more strongly than palmitoyl-CoA, it is suggested that POCA-CoA may inhibit fatty acid synthase directly.

Acetyl-CoA Carboxylase↗