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Biomedical subjects

D Pillay

Publications and source records attributed to D Pillay.

At least 55 records · Page 3Linked to original sources
PubMed2000

Direct visualization and quantitation of cytomegalovirus-specific CD8+ cytotoxic T-lymphocytes in liver transplant patients.

BACKGROUND: CMV infection remains a significant clinical problem in the context of LT. Changes in the magnitude of the CMV-specific CTL response after LT have not previously been assessed but may be important in determining the outcome of CMV infection. METHOD: We used a fluorescent HLA-B*0702-CMV peptide tetrameric complex to directly visualize and quantitate CMV-specific CD8+ CTL both in immunosuppressed patients after LT and in immunocompetent controls. RESULTS: CMV-specific CD8+ CTL, at a frequency ranging from 0.1 to 5.8% of CD8+, were detected in the peripheral blood of 22 of 25 B*0702, CMV immunoglobulin G seropositive individuals, with no difference observed between immunocompetent controls and patients >3 years after LT. In CMV seropositive LT recipients who did not have symptomatic CMV infection during the first 3 months after LT, CMV-specific CD8+ CTL magnitude initially decreased, then increased up to 5 times higher than pre-LT levels within 3 months. Two CMV seronegative recipients of seropositive donors had symptomatic CMV infection in association with high viral load. In both patients, no CD8+ CTL response was detected before the onset of symptoms, and a reduction in viral load was observed during antiviral therapy. However, polymerase chain reaction negativity was achieved only when a demonstrable CMV-specific CD8+ CTL response was generated. Responses were never observed in asymptomatic CMV seronegative patients. CONCLUSIONS: We suggest that the generation of CMV-specific CD8+ CTL may be driven by, and seems to coincide with the suppression of, viral reactivation. Direct monitoring of CMV-specific CD8+ CTL using an HLA-peptide tetramer may prove to be of value in the management of patients after LT.

Blood↗
PubMed2000

Resistance to antiviral drugs in herpes simplex virus infections among allogeneic stem cell transplant recipients: risk factors and prognostic significance.

Herpes simplex virus (HSV) infections in 75 allogeneic stem cell transplant recipients were analyzed. Sixteen patients developed HSV disease following transplantation. The risk factors were age, sex (females), unrelated donor graft, and graft-versus-host disease (GVHD) grade >/=2. Seven patients did not respond to acyclovir, and 3 patients failed to respond to foscarnet. Isolates from 4 patients developed resistance to acyclovir/penciclovir, and 3 patients had foscarnet-resistant isolates. The remaining 3 patients failed to respond to acyclovir, despite having sensitive isolates. All the isolates were sensitive to cidofovir, for which the IC(50) values correlated inversely with those for acyclovir (P=.01). The risk factors for clinical resistance to antiviral drugs were a GVHD grade >/=2 (P=.001) and the lack of ganciclovir prophylaxis (P=.01), with a higher nonrelapse mortality in the latter group (P<.0001). Clinical as well as in vitro resistance to antiviral drugs is common in patients with severe GVHD and is associated with a poor outcome.

Acyclovir↗
PubMed2000

Predictive value of the ultrasensitive HIV viral load assay in clinical practice.

The aim of this study was to determine whether an HIV viral load of <50 copies/ml (c/ml), in the first available plasma sample to have shown a viral load of <400 c/ml, in patients on antiretroviral therapy, is correlated with longer term suppression of viral load (at <400 c/ml) compared to a viral load of 50-399 c/ml, and secondly, to compare the results obtained by ultrasensitive and standard viral load assays carried out on the same sample. A total of 98 HIV-positive patients on antiretroviral therapy with a viral load of <400 c/ml and at least one subsequent viral load measurement, were selected. For each patient, the first available specimen showing a viral load of <400 c/ml was tested using the Roche Amplicor ultrasensitive viral load assay, and patients were followed up subsequently for a median period of 52 weeks. Whether patients achieved an ultrasensitive viral load (USVL) of <50 c/ml or not made very little difference to the proportion of patients in each group showing continued response to treatment (52% vs. 45% respectively). The only variable that was shown to significantly predict longevity of response was the number of antiretroviral drugs used. Secondly, a standard viral load of <400 c/ml but with a detectable signal above background levels, was strongly predictive of a USVL of >50 c/ml. Overall, the findings suggest that the advantage in predictive value of the ultrasensitive over the standard HIV viral load assay, shown previously in clinical trials, may be limited in clinical practice.

Anti-HIV Agents↗
PubMed2000

Preliminary screening of some traditional Zulu medicinal plants for antineoplastic activities versus the HepG2 cell line.

Aqueous and methanol extracts of nine traditional Zulu medicinal plants, Cissus quandrangularis L., Cyphostemma flaviflorum (Sprague) Descoings, Cyphostemma lanigerum (Harv.) Descoings ex Wild & Drum, Cyphostemma natalitium (Szyszyl.) J. v. d. Merwe, Cyphostemma sp., Rhoicissus digitata (L. F.) Gilg & Brandt, Rhoicissus rhomboidea (E. Mey. Ex harv.) Planch, Rhoicissus tomentosa (Lam.) Wild & Drum, R. tridentata (L. F.) Wild & Drum and Rhoicissus tridentata (L. F.) Wild & Drum subsp. cuneifolia (Eckl. & Zeyh.) N. R. Urton, all belonging to the Vitaceae family, were evaluated to determine their therapeutic potentials as antineoplastic agents. The antiproliferative activity in vitro against HepG2 cells was determined. Twenty-two of the twenty-seven crude plant extracts showed activities ranging from 25% to 97% inhibition of proliferation when compared with the control which showed no inhibitory activity. Higher degrees of growth inhibition were found in aqueous root extracts in comparison with the methanol extracts of the same plant parts. The results show potential antineoplastic activity, indicating some scientific validation for traditional usage.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Isolation of viruses from stools in stem cell transplant recipients: a prospective surveillance study.

We prospectively examined stool specimens for enteric viruses in 75 stem cell transplant recipients (autologous 48, allogeneic 27) to determine the frequency and significance of these infections. Only six patients (8%) had a positive isolate. Five of these were allograft recipients (18%) compared to one autograft recipient (2%) (P = 0.02). Unrelated donor BMT recipients were at the highest risk for a viral isolate (OR = 10.5). Adenovirus was the commonest isolate (four patients). One patient each had an echovirus, enterovirus and small round structured virus identified. No correlation was found between the severity of gastro-intestinal symptoms and detection of a viral pathogen. There was no correlation with GVHD or CMV status. The only risk factor identified for isolation of an enterovirus was allogeneic BMT from an unrelated donor. There was a negative correlation with PBSC grafts. All the patients infected with an enteric virus had concomitant infection with other pathogens, compared to only 18% of uninfected patients (P = 0.001). The non-relapse mortality of the infected patients was 50% and only 7% in the uninfected patients (P = 0.01, OR = 12.5), although the isolated virus was the direct cause of death in one patient only. This study indicates a low rate of enteric virus isolation in recipients of PBSC grafts, both autologous and allogeneic. However, unrelated donor BMT is associated with a higher risk of enteric virus infection and an adverse outcome. Bone Marrow Transplantation (2000) 25, 277-282.

Adenoviridae↗
PubMed2000

Adenovirus infections following haematopoietic cell transplantation: is there a role for adoptive immunotherapy?

Adenovirus has been recognised as an important pathogen in BMT recipients, especially in patients with GVHD and those receiving T cell-depleted allografts. We report adenovirus infections from an ongoing surveillance study in four patients after a non-myeloablative transplant and their improved outcome following withdrawal of immunosuppression in two patients and donor lymphocyte infusion for relapsed disease in the others. We discuss the control of adenovirus infections following immune manipulations and the feasibility of adoptive immunotherapy for post-transplant adenovirus infections.

Adenoviridae Infections↗
PubMed2000

Selection of multiresistant hepatitis B virus during sequential nucleoside-analogue therapy.

Hepatitis B virus (HBV) drug resistance to lamivudine is always accompanied by mutations in the viral polymerase gene at position 550, termed group 1 (M550V with L526M) or group 2 (M550I) mutations. The latter mutation has not been associated with famciclovir resistance. Thus, the addition of famciclovir to lamivudine therapy in persons with group 2 lamivudine resistance may lead to virus suppression. The effect of lamivudine/famciclovir combination therapy on HBV infection was monitored in 5 lamivudine-resistant patients by quantitative polymerase chain reaction and polymerase gene sequencing of serum virus. No patients treated with combination therapy had a decline in HBV load >1 log10. Continual evolution of the viral polymerase was detected in association with virologic resistance to both drugs. Cloning experiments identified the preexistence of these multidrug-resistant virus variants as minority species prior to addition of famciclovir therapy. HBV resistance to lamivudine monotherapy is associated with a complex mixture of variants that limit the efficacy of second-line nucleoside-analogue therapy. First-line potent combination therapy may reduce the emergence of HBV drug resistance.

2-Aminopurine↗
PubMed2000

Outcome of lamivudine resistant hepatitis B virus infection in the liver transplant recipient.

BACKGROUND: In many transplant centres lamivudine is an important component of prophylaxis against, and treatment of, hepatitis B virus (HBV) graft infection. Drug resistant HBV species with specific polymerase mutations may emerge during lamivudine treatment. AIMS: To examine the clinical consequences of graft infection by lamivudine resistant virus. METHODS: The clinical course of four liver transplant patients who developed graft infection with lamivudine resistant virus was reviewed. The response of HBV infection to reduction of immunosuppression and to manipulation of antiviral therapy was assessed. For each patient, serum viral titre was measured and the viral polymerase gene was sequenced at multiple time points. RESULTS: High serum titres were observed following emergence of the lamivudine resistant species. Wild type HBV re-emerged as the dominant serum species after lamivudine withdrawal. All patients developed liver failure, and onset of liver dysfunction was observed when resistant virus was the dominant serum species. In three patients, liver recovery was observed when immunosuppression was stopped and when alternative antivirals were given. Wild type virus appeared to respond to ganciclovir, and to reintroduction of lamivudine. For one patient, introduction of famciclovir was associated with clinical, virological, and histological response. CONCLUSIONS: Failure of lamivudine prophylaxis may identify patients at special risk for the development of severe graft infection. Treatment of graft reinfection should include reduction of immunosuppression, and systematic exposure to alternative antivirals. Viral quantitation and genetic sequencing are essential components of therapeutic monitoring.

Adult↗
PubMed2000

Additive antiviral effects of lamivudine and alpha-interferon in chronic hepatitis B infection.

alpha-Interferon has limited efficacy against chronic hepatitis B virus (HBV) infection. Nucleoside analogues may confer greater benefits, however, it is likely that combination therapies will be required for effective control of this infection. We investigated the antiviral effect of lamivudine and interferon therapy in eight patients with high HBV-DNA levels. Six patients received lamivudine/interferon combination therapy followed, after a 6-month drug-free period, with lamivudine monotherapy. Mean HBV viral load (copies/ml) reduction was significantly greater after 4 months of combination therapy (4.3 x 10(3)) compared to an equivalent period of lamivudine monotherapy (2.9 x 10(2)) (P=0.03). Two patients were given 6 months of lamivudine/interferon combination therapy followed immediately by lamivudine monotherapy. Cessation of interferon in these patients led to a rapid 1-2 log10 increase in HBV viral load. These findings suggest that alpha-interferon has a direct antiviral effect on chronic HBV infection, which may be additive to, or synergistic with lamivudine.

Antiviral Agents↗
PubMed2000

Transradial coronary angioplasty and stenting--immediate results and 3-month clinical follow-up in the first 50 patients performed at the National Heart Institute.

AIM: To explore the safety and feasibility of coronary angioplasty and stenting via the radial artery in a heterogenous group of patients and to report the immediate and 3-month clinical follow-up. BACKGROUND: The use of the transradial approach for coronary angiography was first described by Lucien Campeau in 1989. Based on the favourable initial results, this technique has gained widespread acceptance worldwide. Ferdinand Kiemeneij's work in transradial angioplasty and stenting has taken invasive cardiology into the exciting new era of "minimally invasive coronary intervention". METHODS AND RESULTS: Fifty consecutive patients underwent Transradial Percutaneous Transluminal Coronary Angioplasty (PTCA) with or without stenting from mid March 98-December 98. The right radial approach was utilised in 41 patients (80%) while the left in 9 patients. Ninety percent of the procedures was done on an adhoc basis. Diabetes mellitus was present in 38% of patients. Eighty percent of patients had unstable angina pectoris and 60% had a prior history of acute myocardial infarction. The commonest vessel involved was the LAD (51%) and type B lesions predominated (54%). PTCA was successful in 96%. One patient had a total LAD occlusion, which could not be wired, and another developed severe spasm during catheter manipulation. The latter had successful PTCA via the right femoral route Stents were utilised in 57% of patients. The commonest indication for stenting was suboptimal PTCA results (89%) and dissection (14%). There was no stent embolisation and all stents were successfully deployed (100%). One patient developed acute stent thrombosis necessitating repeat PTCA and another patient sustained an acute anteroseptal myocardial infarction 5 days post procedure as a result of subacute stent thrombosis and died. Two patients had successful primary PTCA. There was no bleeding or vascular complications. 60% of patients were treated on an outpatient basis. At 3-months follow up, 1 patient required CABG's for disease progression. Three patients had absent radial pulses without adverse consequence. No patient required repeat PTCA at follow up. CONCLUSION: In summary, adhoc PTCA and stenting is safe and feasible in our patient population. A study on the cost effectiveness of the procedure compared to conventional femoral PTCA is warranted.

Angioplasty, Balloon, Coronary↗
PubMed1999

Significance testing of clinical data using virus dynamics models with a Markov chain Monte Carlo method: application to emergence of lamivudine-resistant hepatitis B virus.

Bayesian analysis using a virus dynamics model is demonstrated to facilitate hypothesis testing of patterns in clinical time-series. Our Markov chain Monte Carlo implementation demonstrates that the viraemia time-series observed in two sets of hepatitis B patients on antiviral (lamivudine) therapy, chronic carriers and liver transplant patients, are significantly different, overcoming clinical trial design differences that question the validity of non-parametric tests. We show that lamivudine-resistant mutants grow faster in transplant patients than in chronic carriers, which probably explains the differences in emergence times and failure rates between these two sets of patients. Incorporation of dynamic models into Bayesian parameter analysis is of general applicability in medical statistics.

Antiviral Agents↗
PubMed1999

Respiratory viruses in adult liver transplant recipients.

BACKGROUND: The contribution of respiratory viruses to respiratory disease in adult liver transplant (LT) recipients has not been studied. We performed a prospective audit to document the incidence of respiratory syncytial viruses ([RSVs], parainfluenza virus, influenza virus, and adenovirus) after LT, and to determine their contribution to respiratory disease in this setting. METHODS: Consecutive adult recipients were followed for 8 months after LT. Throat swabs were collected weekly for up to 12 weeks after LT, and virological surveillance was performed using conventional techniques (direct immunofluorescence and cell culture). A polymerase chain reaction assay for RSV was subsequently performed on selected specimens. Clinical data, including episodes of respiratory disease, were also recorded. RESULTS: During the study period, 51 patients received 53 LT. Five patients died, but no viruses were isolated from these patients at any stage. A total of 323 swabs were examined by conventional techniques and yielded 35 viral isolates (10.8%). Herpes simplex virus (type 1) accounted for 33 isolates, none of which were associated with respiratory disease. Two of 323 swabs (0.62%), in 2 patients, yielded respiratory viruses (both RSV); both patients had self-limiting, mild, upper respiratory tract symptoms. In these 2 patients, the polymerase chain reaction assay was more sensitive than conventional techniques and was able to detect extended RSV excretion. Of 51 recipients, 31 (61%) were always negative for viruses. Of 51 recipients, 10 developed respiratory failure, but no respiratory viruses were isolated from any of these patients. CONCLUSIONS: Respiratory viruses are rarely isolated from adult recipients after LT and are not associated with serious morbidity or with mortality. Routine surveillance for respiratory viruses in this patient population is not justified on the basis of this study.

Adenoviridae Infections↗
PubMed1999

High pre-treatment serum hepatitis B virus titre predicts failure of lamivudine prophylaxis and graft re-infection after liver transplantation.

BACKGROUND/AIMS: Orthotopic liver transplantation has an established role for the treatment of patients with chronic liver failure secondary to hepatitis B virus (HBV) infection. Unfortunately, recurrent infection of the graft can be associated with aggressive disease, and with diminished graft and patient survival. Currently, the role of nucleoside analogues for prevention of graft re-infection is being evaluated. Preliminary results are encouraging, but treatment failure has been associated with emergence of drug-resistant virus. METHODS: We have studied ten consecutive patients who received lamivudine prophylaxis for prevention of HBV graft reinfection. Sequential sera, collected prelamivudine then during treatment before and after liver transplantation, were examined. Conventional serological markers were measured, as were serum viral DNA levels with a sensitive quantitative polymerase chain reaction assay. RESULTS: Lamivudine treatment effected a reduction in serum HBV levels, but six patients still had measurable viral DNA at the time of transplantation. Five patients developed graft re-infection with lamivudine-resistant virus. Resistant virus emerged 8 to 15 months post-transplant. The likelihood of emergence of resistant virus was related to the pre-treatment serum HBV titre. Persistent serum viral DNA positivity and evidence of graft re-infection during the early post-transplant period did not predict the subsequent emergence of resistant virus. CONCLUSIONS: Our observations suggest that the resistant species may be present in the viral quasispecies in the serum and liver of patients with high-level replication prior to lamivudine exposure. The resistant species can persist during lamivudine treatment prior to transplantation, and emerge following transplantation. These observations suggest strategies which might prevent the emergence of drug-resistant species, and imply that graft re-infection may be a preventable phenomenon.

Antiviral Agents↗