PubMed Health⌕ Search

Biomedical subjects

P Reusser

Publications and source records attributed to P Reusser.

At least 19 recordsLinked to original sources
PubMed2005

Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time.

We analysed a large homogeneous group of 14,403 patients transplanted for early leukaemia from an HLA-identical sibling and reported to the EBMT in four time cohorts: 1980-1989 (24%), 1990-1994 (26%), 1995-1998 (30%) and 1999-2001 (20%). We focused on death from infection. End points were survival, death from relapse and transplant-related mortality (TRM), which was subdivided into death from graft-versus-host disease (GvHD) (1315 patients; 25% of deaths), infection (597 patients; 11% of deaths) or 'other' causes (1875 patients; 34% of deaths). Survival increased from 52% at 5 years in the first to 62% in the third cohort (P<0.05) and TRM decreased from 36 to 26% (P<0.05) due to a reduction in death from infection (P<0.001). GvHD, 'other' causes and relapse did not improve. The relative proportions of bacteria (217 patients; 36%), viruses (183 patients; 31%), fungi (166 patients; 28%) or parasites (32 patients; 5%) as cause of infectious death (cumulative incidence of death at 5 years 1.8, 1.6, 1.4 and > or = 0.3%, respectively) and median time to death from infections (3 months (range 0-158 months)) did not change. Death from infections has been reduced significantly, but it still represents an ongoing risk after HSCT and draws attention to the time beyond the initial period of neutropenia.

Adolescent↗
PubMed2001

Oral valganciclovir: a new option for treatment of cytomegalovirus infection and disease in immunocompromised hosts.

Immunocompromised hosts are at increased risk of cytomegalovirus (CMV) infection and serious CMV disease. CMV infection is an important cause of morbidity among patients infected with HIV and after solid organ transplantation (SOT) and may cause life-threatening disease in allogeneic stem cell transplant (SCT) recipients. The introduction into clinical use of potent antiviral compounds and of rapid detection assays for CMV during the past two decades has allowed development of strategies for the prevention and treatment of disease caused by CMV in these groups of immunocompromised patients. At present, the antiviral drugs ganciclovir, foscarnet and cidofovir are commonly used in the treatment of CMV infection and disease. However, these agents have a poor oral bioavailability and, for systemic use, require iv. administration for most indications. Valganciclovir is an oral prodrug of ganciclovir, with a 10-fold greater bioavailability than oral ganciclovir. Studies of the pharmacokinetics of valganciclovir among HIV-infected CMV-seropositive patients and liver transplant recipients suggest that this oral compound has the potential to replace both oral and iv. ganciclovir in many situations if it is shown to be as efficacious and safe as those ganciclovir formulations in immunodeficient patients. In the first part of this review, currently established approaches to the management of CMV infection and disease in SCT and SOT recipients and HIV-infected patients are discussed to highlight possible indications for future valganciclovir use; in the second part, data from human studies of valganciclovir are presented.

Administration, Oral↗
PubMed2000

Antiviral therapy: current options and challenges.

This article reviews current options and concepts for drug treatment of viral infections with the exception of human immunodeficiency virus infection. Advances in antiviral drug development and in rapid diagnostic methods have resulted in efficient management strategies, particularly for infections due to herpes simplex virus, varicella-zoster virus, cytomegalovirus, influenza A and B viruses, and chronic hepatitis B and C. Newer antiviral agents, such as valaciclovir and famciclovir, have a high oral bioavailability which permits less frequent intake and avoidance of intravenous therapy in many cases. As an alternative to subcutaneous interferon-alpha (IFN-alpha) treatment, oral lamivudine is now approved for therapy of chronic hepatitis B. The addition of oral ribavirin to IFN-alpha treatment has been shown to be superior to IFN-alpha alone for therapy of chronic hepatitis C. By contrast to amantadine, neuraminidase inhibitors such as zanamivir or oseltamivir (GS4104) have activity against both influenza A and B viruses and are well tolerated. First results of controlled trials with these agents are discussed. The emergence of herpes virus resistance to antiviral drugs is of concern, and validation of alternative treatment for patients with documented resistance is required. Future investigations may also help to clarify the therapeutic role of novel antiviral drugs and formulations, such as the oral prodrug of cidofovir, valganciclovir, compounds 1263W94 and Bay 38-4766, and pleconaril.

Antiviral Agents↗
PubMed1999

Cytomegalovirus (CMV)-specific T cell immunity after renal transplantation mediates protection from CMV disease by limiting the systemic virus load.

The role of cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTLs) and T helper cells (Th) in controlling CMV infection, as detected by antigenemia assay and polymerase chain reaction (PCR) in blood leukocytes, and CMV disease was investigated in 20 renal transplant recipients. Within 3 months after transplant, CMV-specific CTL and Th responses were demonstrable in 11 (55%) and 15 (75%) patients, respectively; CMV infection was detected by antigenemia and PCR in 19 (95%) patients each. During the month of first CMV detection, there was an inverse correlation between CTL response and antigenemia at >/=20 positive cells/105 leukocytes (P=.007) but no association with lower antigenemia levels or PCR positivity. CMV disease developed in 7 (35%) patients and was associated with high-level antigenemia but was inversely correlated with detection of CTLs (P=.04). After renal transplantation, CMV-specific CTLs limit the systemic virus load as reflected by antigenemia levels and thereby mediate protection from CMV disease.

Adult↗
PubMed1998

[Chylothorax as the initial manifestation of malignant Hodgkin lymphoma].

A 22 year-old man complaining of slight thoracic pain, was found to have a right pleural effusion in his chest X-ray. The pleural aspiration yielded chylous fluid and radiological examination and biopsy of a mediastinal mass led to the diagnosis of Hodgkin's disease of the nodular sclerosis type with supra- and radiologically infradiaphragmatic disease and a pathological fracture of the sternum. After complete initial aspiration of the pleural effusion the chylothorax did not recur following initiation of a combination chemotherapy, and a clear regression of the lymphoma was found after the first 3 cycles. This case provides an example of an oligosymptomatic, right sided chylothorax as the first manifestation of Hodgkin's disease in a young immuno-competent patient.

Adult↗
PubMed1998

[Pulmonary tuberculosis with resistance to 4 antitubercular drugs].

A 32-year-old immigrant from Pakistan was admitted to our hospital with cavernous pulmonary tuberculosis. He gave a history of several 1 to 2-months courses of antimycobacterial treatment administered earlier in Pakistan. We initiated combined therapy including isoniazid, rifampin, pyrazinamide, and ethambutol. Subsequently, results of susceptibility testing from M. tuberculosis-complex strains isolated before the onset of treatment documented the presence of resistance against both isoniazid and rifampin which may have been primary or acquired drug resistances. During the course of treatment, two additional resistances to pyrazinamide and ethambutol developed which were probably due to the initial therapy with only two active antimycobacterial agents. The emergence of multidrug-resistant strains of M. tuberculosis complex is a world-wide problem. Our case indicates that multiresistance must be considered in every patient presenting with tuberculosis. If there is a strong suspicion of multidrug-resistant tuberculosis, initial treatment with a combination of 5-6 antimycobacterial agents seems advisable until the results of susceptibility testing become available.

Adult↗
PubMed1998

Current concepts and challenges in the prevention and treatment of viral infections in immunocompromised cancer patients.

Patients with acute leukemia treated with intensive chemotherapy and recipients of bone marrow or peripheral blood stem cell transplants are at high risk of serious viral disease. Recent progress in diagnostic methods and in antiviral drug treatment has permitted the development of efficient management strategies particularly for infections due to herpes simplex virus, varicella-zoster virus, and cytomegalovirus in these patients. By contrast, specific treatment of other virus infections in immunocompromised cancer patients remains an unresolved issue. The emergence of herpesvirus resistance to antiviral drugs is a matter of concern, and its clinical importance among patients with malignancy needs to be elucidated. Future investigations may furthermore help to clarify the role of novel antiviral agents, such as cidofovir, lobucavir, and compound 1263W94, and of the adoptive immunotherapy with virus-specific CTL clones in severely immunodeficient cancer patients.

Antiviral Agents↗
PubMed1997

Cryptococcosis, epileptic seizures and encephalopathy in a HIV-infected patient.

We report on a 32-year old HIV-infected male patient who was admitted to the hospital in a comatose state. A cryptococcus neoformans septicemia with meningoencephalitis was diagnosed. Intravenous treatment with amphotericin B was initiated and replaced three weeks later by fluconazole per os. With this therapy the patient recovered quite well. However, following two grand mal epileptic seizures he suddenly fell into a deep coma 22 days after admission to the hospital. The cause of the encephalopathy remained unclear, and the patient died 2 days later. Autopsy revealed a severe meningoencephalitis and a pneumonia due to cryptococcus neoformans. Departing from this case we discuss diagnosis, clinical presentation and treatment of cryptococcus meningoencephalitis.

AIDS-Related Opportunistic Infections↗
PubMed1997

Cytomegalovirus-specific T-cell immunity in recipients of autologous peripheral blood stem cell or bone marrow transplants.

The cytomegalovirus (CMV)-specific CD8+ cytotoxic T-lymphocyte (CTL) and CD4+ T-helper cell (Th) functions were characterized in 15 CMV seropositive recipients of autologous peripheral blood stem cell or bone marrow transplants. These immune functions were evaluated in peripheral blood specimens obtained before and at 1, 2, and 3 months after transplant. For study of CTL activity, blood mononuclear cells were cocultured with CMV-infected autologous fibroblasts for 2 weeks and then tested for cytotoxicity against CMV-infected or mock-infected autologous and HLA-mismatched fibroblasts. The Th response to CMV antigen was assessed by standard lymphoproliferative assay. CMV-specific CD8+ CTL and CD4+ Th responses were detectable in 12 (80%) and 14 (93%) patients, respectively, in the first 3 months after transplantation. A Th response to CMV was always present by the time of first CTL detection. During the posttransplant period, CMV infection occurred in 6 (40%) patients, and detection of CMV-specific CD8+ CTL activity was associated with protection from subsequent CMV infection (P = .002). Among CMV seropositive autograft recipients, CMV-specific CD8+ CTL and CD4+ Th responses are restored in a large proportion of patients in the first 3 months after transplantation, and the presence of a specific CD8+ CTL activity affords protection from CMV infection.

Adolescent↗
PubMed1996

[An unusual presentation of tuberculosis].

A 67-year-old male was hospitalized because of nonspecific symptoms and bilateral pleural effusions. He gave no history of cough, dyspnea or thoracic pain. The blood counts showed moderate anemia and high-grade lymphopenia. The tuberculin test and the anergy-panel were both negative. Testing for HIV was negative. Analysis of pleural fluid showed an exudate with 47% lymphocytes and absence of acid-fast bacilli on Ziehl-Neelsen smear. On histologic examination, the pleural tissue showed no evidence of granuloma. However, cultures for mycobacteria of pleural tissue yielded M. tuberculosis. In this case of pleural tuberculosis, leading symptoms were absent and the tuberculin test was negative in the presence of active tuberculosis. In addition, the cells in the pleural effusion were not predominantly lymphocytic. Patients presenting with unclear effusion should undergo extensive investigations, including a tuberculin test, and anergy panel, pleural fluid cultures, and pleural biopsy with cultures for microorganisms, with the object of establishing or ruling out pleural tuberculosis.

Aged↗
PubMed1996

[Ganciclovir-resistant cytomegalovirus infection: 2 cases with different clinical impact].

Swiss cases of cytomegalovirus (CMV) resistance to antiviral drugs have not been reported to date. We describe both a documented and a presumed case of ganciclovir-resistant CMV infection. A bone marrow transplant recipient with an episode of CMV viremia and antigenemia underwent broncho-alveolar lavage from which a CMV strain was isolated. The sensitivity of this strain to ganciclovir and foscarnet was tested in a plaque reduction assay, which was performed in 6 different fibroblast lines. The inhibitory drug concentration which reduced viral plaque formation by 50% (IC50) was a median of 12.7 microM (range 6.1-29.6) for ganciclovir (resistance defined as IC50 > 6 microM), which documented the presence of CMV resistance to ganciclovir. The strain was sensitive to foscarnet. This ganciclovir-resistant CMV strain had no clinical impact, although the patient was treated with ganciclovir. A second patient had Aids and subsequently developed CMV retinitis which was treated with intravenous ganciclovir for 3 weeks, followed by longterm oral ganciclovir therapy. Approximately 4 1/2 months after initiation of antiviral therapy the patient developed fatal CMV multi-organ disease while on continued oral ganciclovir treatment, which suggested the occurrence of CMV resistance to this agent. CMV organ disease was documented at autopsy by histology and immunochemistry, but virus was not cultured. The different outcomes in these two patients suggest that the type of underlying immunodeficiency may be a decisive factor for the clinical relevance of drug-resistant CMV infection.

AIDS-Related Opportunistic Infections↗
PubMed1996

Herpesvirus resistance to antiviral drugs: a review of the mechanisms, clinical importance and therapeutic options.

During the past decade, potent agents against herpes simplex virus (HSV) types 1 and 2, varicella zoster virus (VZV), and cytomegalovirus (CMV) have become available. The increasing clinical use of acyclovir, ganciclovir, and foscarnet has been associated with the emergence of drug-resistant herpesvirus strains. Resistance to acyclovir or ganciclovir most frequently results from deficient intracellular phosphorylation of these agents which is required for drug activation. Resistance to foscarnet is due to viral DNA polymerase mutants that permit viral replication despite the presence of the drug. In immunocompetent patients, herpesvirus resistance is rare and generally does not correlate with clinical outcome. In contrast, in immunocompromised hosts, resistance of HSV, VZV, and CMV is increasingly detected, and may be associated with disease refractory to antiviral therapy. Foscarnet treatment has been used with some clinical benefit in patients with acyclovir-resistant HSV or VZV, or ganciclovir-resistant CMV. For therapy of resistant mucocutaneous HSV disease, topical trifluorothymidine, and topical or intravenous cidofovir (HPMPC) have yielded encouraging results that warrant further investigation. Improved methods for detection of herpesvirus resistance, and validation of alternative therapy for patients with documented resistance are required to reduce the clinical impact of drug-resistant herpesviruses.

2-Aminopurine↗
PubMed1996

European survey of herpesvirus resistance to antiviral drugs in bone marrow transplant recipients. Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

A survey of herpesvirus resistance to antiviral drugs was conducted by mailing a questionnaire to the centers of the European Group for Blood and Marrow Transplantation (EBMT). Results from 68 centers were reported. The number of centers with proven or suspected resistance of herpes simplex virus (HSV) was 17 (25%), of varicella-zoster virus (VZV) was three (4%), and of cytomegalovirus (CMV) was 19 (28%). Acyclovir-resistant HSV strains were recovered from 10 patients with HSV disease. Replacement of acyclovir by foscarnet in seven of these patients resulted in improved or healed HSV disease in five (17%). Acyclovir-resistant VZV was isolated from one patient with zoster which improved after a change to vidarabine therapy. CMV resistance to ganciclovir was proven in only two patients but was suspected in 23. Ganciclovir was replaced by foscarnet in 15 of these 25 patients which resulted in better virological and/or clinical outcome in 13 (87%). These results suggest that herpesvirus resistance is an emerging problem in marrow transplant recipients, and that foscarnet treatment may prove to be a valuable alternative when the presence of acyclovir- or ganciclovir-resistant herpesvirus disease is documented in these patients.

Acyclovir↗
PubMed1995

Failure of high-dose acyclovir to prevent cytomegalovirus disease after autologous marrow transplantation.

In a retrospective study, the strategy of giving high-dose acyclovir (500 mg/m2 every 8 h intravenously) from day 5 before transplantation to day 30 after transplantation was evaluated in 266 cytomegalovirus (CMV)-seropositive autograft recipients. the incidence of CMV pneumonia was compared with that in 85 control patients who did not receive high-dose acyclovir. There was no significant difference in the incidence of CMV pneumonia between groups at day 100 (Kaplan-Meier estimates, 6.3% [acyclovir] vs. 7.7% [controls], P = .63) and day 200 after transplantation (7.6% vs. 13.1%, P = .32). The overall rate of patients who presented with CMV disease without preceding excretion from blood, urine, or throat was 77%. CMV pneumonia was fatal in 9 (56%) of 16 acyclovir recipients compared with 5 (63%) of 8 controls (P = 1.0). Survival after transplantation was not different between groups (P = .68). Thus, high-dose acyclovir does not appear to be effective for prevention of CMV disease after autologous transplantation.

Acyclovir↗
PubMed1995

Immunisations after bone marrow transplantation: results of a European survey and recommendations from the infectious diseases working party of the European Group for Blood and Marrow Transplantation.

Increased numbers of recipients of BMTs and autologous BMTs are becoming long-term survivors. Existing data support that loss of protective immunity to agents such as tetanus and poliovirus is common in patients who received BMTs and autologous BMTs. Thus, a reimmunisation programme is needed to ensure immunity. A questionnaire concerning immunisation practices was sent to EBMT member centres. The immunisation practices varied extensively in the 59 responding BMT and 48 responding autologous BMT centres. Sixty five per cent of responding centres routinely immunise patients who received allogeneic BMTs whereas 37% were routinely immunising recipients of autologous BMTs. Tetanus toxoid and inactivated poliovirus vaccine were the most frequently used vaccines in both BMT and autologous BMT centres. Immunisations of recipients of both BMTs and autologous BMTs with tetanus toxoid, diphtheria toxoid, inactivated poliovirus vaccine and influenza vaccine are recommended. Other vaccines, and in particular live attenuated vaccines, may be considered on an individual basis.

Bone Marrow Transplantation↗