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P Reusser

Publications and source records attributed to P Reusser.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Early diagnosis of cytomegalovirus infection and disease in patients following kidney transplantation].

For early diagnosis of cytomegalovirus (CMV) infection after renal transplantation, 18 patients were monitored within the first 3 months. Blood leukocytes were assayed weekly for the presence of the CMV matrix protein p65 (antigenemia assay) and CMV DNA by the polymerase chain reaction (PCR). In 12 out of 18 patients, 70 (37.8%) of 185 blood samples were positive by antigenemia assay or by PCR. 49 and 115 samples concurrently were positive and negative by both tests. 8 blood samples were positive only by the antigenemia assay and 13 only by PCR. Therefore, the relative sensitivity of PCR and of antigenemia assay was 88.6% and 81.4% respectively. In 9 of 10 patients who were pre-transplant CMV seropositive and in 4 of 7 patients who were pre-transplant CMV seronegative and received a graft from a seropositive donor, CMV infection was detected by positive antigenemia and/or PCR. Four of these patients developed CMV disease. In all these patients, antigenemia assay and PCR were positive 7 to 16 days prior to onset of clinical symptoms. Antigenemia and PCR are rapid and sensitive methods for the detection of CMV infection 1 to 2 weeks prior to disease. In addition, the semi-quantitative assay of antigenemia enables monitoring of the efficacy of antiviral therapy.

Cytomegalovirus↗
PubMed1994

[Resistance to virostatic agents in Herpes viruses: mechanism, incidence and clinical significance].

Following the introduction of potent antiviral agents against herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV) into clinical use, the isolation of resistant virus strains has been reported with increasing frequency. The first part of this overview focuses on the mechanisms of action of acyclovir, ganciclovir, and forcarnet, and on the mechanisms of viral resistance. In the second part, the incidence and clinical importance of resistant herpes viruses are discussed. Among immunocompetent patients, herpes virus resistance is a rare event even in the case of long-term treatment with acyclovir for suppression of genital herpes. By contrast, among immunocompromised hosts, the isolation of resistant herpes virus strains from patients with disease unresponsive to antiviral drugs is not infrequent. The incidence of acyclovir-resistant HSV isolates in two large studies was 5%, and that of ganciclovir-resistant CMV strains was reported to be about 7%. At present, data on infections due to resistant VZV strains are scarce. Results from case reports and small series suggest some clinical benefit from the use of foscarnet when acyclovir-resistant HSV or VZV is present, or when CMV disease is caused by ganciclovir-resistant strains. Broader use of susceptibility testing to antiviral drugs and the development of new antiherpetic agents are required to improve the diagnosis and treatment of disease due to resistant herpes viruses.

Acyclovir↗
PubMed1994

Impact of liver disease and hepatitis infections on allogeneic bone marrow transplantation in Europe: a survey from the European Bone Marrow Transplantation (EBMT) Group--Infectious Diseases Working Party.

This survey investigated allogeneic bone marrow transplantation (BMT) policy in European BMT units by questionnaire, in relation to pre-transplant liver disease. It also assessed diagnostic standards for viral hepatitis infections and their prevalence in BMT candidates. Sixty-three EBMT centers from 22 countries participated in the survey. Median pre-transplant prevalences of HBsAg and anti-HCV positivity were 3.5% (range 0-15%) and 5% (range 0-45%), respectively. Forty-six (73%) centers adopt the policy of cancelling or postponing BMT in patients with ALT abnormalities but in four of these centers, BMT is not delayed when progressive disease or acute leukemia is present. In 17 institutions (27%) BMT was reported to be carried out irrespective of transaminase values. Data on fatal post-BMT liver disease were provided by 45 centers. The overall mortality rate for liver failure was 4.5% (258 of 5788) with no differences between centers performing or not performing BMT in cases of ALT elevation. These results indicate that there is strong concern in most European BMT units about performing BMT in the presence of ALT elevation and prospective studies on its real impact on fatal post-BMT liver disease should be conducted.

Alanine Transaminase↗
PubMed1993

Practices for cytomegalovirus diagnosis, prophylaxis and treatment in allogeneic bone marrow transplant recipients: a report from the Working Party for Infectious Diseases of the EBMT.

During the past few years major progress has been made in the diagnosis and therapy of CMV infection after allogeneic BMT. The aim of this survey was to investigate the use of diagnostic techniques, use of prophylaxis and the therapeutic strategies among members of the EBMT. Seventy centers from 20 countries responded to the survey. Sixty-seven centers (96%) routinely tried to diagnose CMV from the blood. Fifty-seven centers used standard or rapid isolation techniques. Thirty-seven centers used one of the newly developed techniques, antigenemia detection in leukocytes or PCR together with isolation, while 10 centers used one of these two techniques without standard isolation. Fifty-five centers regularly performed bronchoscopy and bronchoalveolar lavage on the suspicion of CMV pneumonia but only 12 centers required detection of CMV in specimens from the lavage or lungs as the indication to start therapy; 31 centers started therapy on symptoms of pneumonia combined with CMV detection from any site. Prophylaxis was used in 54 centers (84%). The most commonly used regimen was high-dose acyclovir which was used by 42 centers, while seven centers used ganciclovir. The strategy of early therapy was used by 53 centers (76%) and was most frequently based on detection of viremia or CMV antigen in the blood. CMV pneumonia was treated by a combination of ganciclovir and i.v. immunoglobulin by 64 centers, by foscarnet and immunoglobulin in 5 centers and by ganciclovir alone in 5 centers. CMV gastrointestinal disease was treated by antiviral therapy alone in 18 centers and by a combination of antiviral therapy and iv immunoglobulin in 46 centers.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗
PubMed1992

Phase I-II trial of foscarnet for prevention of cytomegalovirus infection in autologous and allogeneic marrow transplant recipients.

The safety and efficacy of foscarnet for prevention of cytomegalovirus (CMV) infection was evaluated in 19 CMV-seropositive bone marrow transplant (BMT) recipients. All patients received intermittent intravenous (iv) foscarnet: 40 mg/kg every 8 h from 7 days before to day 30 after BMT, then 60 mg/kg once a day until day 75. The main toxicity was transient renal dysfunction, with a greater than 50 mumol/L increase in serum creatinine above baseline in 5 of the 7 autograft recipients and in 6 of the 12 allograft recipients. Only 4 allograft recipients developed CMV infection during foscarnet prophylaxis, and no patient showed evidence of CMV disease. Because 3 allograft recipients receiving concomitant iv amphotericin B showed rapid impairment of renal function, foscarnet prophylaxis should not be given to allograft recipients requiring amphotericin B; otherwise, foscarnet prophylaxis at this dose appears safe after BMT.

Adolescent↗
PubMed1991

Development of a treatment regimen for human cytomegalovirus (CMV) infection in bone marrow transplantation recipients by adoptive transfer of donor-derived CMV-specific T cell clones expanded in vitro.

CMV infection represents a major cause of morbidity and mortality in immunosuppressed bone marrow transplant (BMT) recipients. Life-threatening CMV infection was found to occur only in patients who did not develop a CMV-specific CD8+ Tc response. Therefore, methods to clone and expand CMV-specific Tc were developed to facilitate analysis of the specificity of the CD8+ Tc response to CMV responsible for protective immunity in seropositive donors, and to permit adoptive transfer of in vitro expanded CMV-specific Tc derived from bone marrow donors into immunocompetent HLA-matched BMT recipients to augment resistance to CMV. The immunodominant class I-restricted Tc response present in healthy seropositive individuals was found to be specific for a conserved CMV antigen introduced into the cytoplasm and presented shortly following viral penetration and uncoating, and did not require endogenous viral gene expression and protein synthesis. Thus, the protective immune response to CMV mediates lysis of virally-infected cells prior to virion assembly. Processing of viral proteins and access to presentation in the context of class I MHC molecules immediately following infection of target cells was selective for internal virion proteins, such as the tegument protein pp65. By contrast, presentation by infected cells of GB, the major CMV envelope protein, or IE, the major regulatory protein, was delayed due to a requirement for endogenous synthesis in infected cells, and CD8+ Tc specific for these proteins were detected in low frequency as compared to the immundominant response.

Antigens, Viral↗
PubMed1991

Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease.

The high rate of severe cytomegalovirus (CMV) disease after bone marrow transplantation (BMT) is related to the profound immunodeficiency posttransplant. Because cytotoxic T lymphocytes (CTL) have been implicated in resistance to viral infections, we examined the restoration of the CMV-specific CTL response in 20 patients who received bone marrow from HLA-matched, CMV-seropositive donors. Blood specimens were obtained from patients at 1, 2, and 3 months after BMT and from the donors on a single occasion. Peripheral blood mononuclear cells were cocultured with CMV-infected donor-derived fibroblasts for 2 weeks and then tested for cytotoxicity against CMV-infected and uninfected autologous or HLA-mismatched fibroblasts. Cytolytic activity was detected in all 20 donors, with specificity for autologous CMV-infected targets demonstrable in 17 (median CMV-specific lysis at an effector:target ratio of 15:1 was 32%, range 18% to 83%). Specific lysis was mediated by CD8+, class I-restricted T cells, as shown by inhibition with anti-class I monoclonal antibody and by selective depletion of effector cells. By contrast, CMV-specific CTL were detected in only 10 of 20 patients after BMT (median lysis 29% at 3 months post-BMT). None of these 10 patients developed CMV pneumonia, whereas 6 of the 10 patients with an undetectable CMV-specific CTL response after BMT died with CMV pneumonia. These results demonstrate that restoration of CMV-specific CTL responses may require an extended time period after BMT in some patients, and that such patients are at increased risk of developing severe CMV disease. Approaches to reconstitute CMV immunity in BMT patients by adoptive transfer of CMV-specific CD8+ CTL clones derived from the bone marrow donor are now being pursued.

Adolescent↗
PubMed1990

Cytomegalovirus infection after autologous bone marrow transplantation: occurrence of cytomegalovirus disease and effect on engraftment.

Epidemiologic and clinical characteristics of cytomegalovirus (CMV) infection and disease were analyzed retrospectively in 159 autologous marrow transplant recipients. The probability of CMV infection by day 100 after transplant was 22.5% in patients seronegative to CMV before transplant versus 61.1% in seropositive patients (P less than .0001 by logrank test). Multivariate analysis identified positive pretransplant CMV serology as the only definable risk factor for CMV infection (relative risk 1.4, P less than .0001). CMV pneumonia developed in 11 patients at a median time of 100 days after transplant and was fatal in nine cases. CMV pneumonia was associated with significantly decreased probability of survival by day 100 after transplant (relative risk of death of 16.7, P less than .0001). In contrast to earlier reports, CMV infection had no significant effect on the rapidity of platelet or neutrophil recovery after transplant as assessed by time-dependent multivariate analysis. Because the incidence of severe CMV disease is not negligible after autologous marrow transplantation, preventive measures against CMV infection are warranted, as in allogeneic marrow transplantation.

Adult↗
PubMed1990

Prospective endoscopic study of stress erosions and ulcers in critically ill neurosurgical patients: current incidence and effect of acid-reducing prophylaxis.

We studied prospectively 40 critically ill neurosurgical patients who required prolonged mechanical ventilation to determine the current incidence of stress-related gastroduodenal erosions and ulcers, and to assess endoscopically the efficacy of acid-reducing prophylactic treatment. Nineteen patients were randomized to receive ranitidine plus antacids if necessary to maintain gastric pH at greater than or equal to 4. The remaining 21 patients were given no drug prophylaxis. Gastric pH was significantly (p less than .001) higher in the treated group: 78% of pH readings were at greater than or equal to 4 as compared to 32% in the control group. However, after five study days, incidence and severity of stress lesions were similar in the two groups: nine patients in each group had more than five erosions, one treated patient had a gastric ulcer, and one control patient had duodenal ulcerations. No patient experienced clinically relevant upper GI bleeding. The lack of severe stress bleeding and the low ulcer rate contrast with results from earlier reports on similar patient populations. Furthermore, drug prophylaxis had no detectable benefit, as assessed endoscopically. These findings suggest that routine stress lesion prophylaxis may not be necessary in critically ill patients with comparable risk factors.

Adolescent↗
PubMed1989

Role of gastric colonization in nosocomial infections and endotoxemia: a prospective study in neurosurgical patients on mechanical ventilation.

The role of gastric microbial colonization in nosocomial infections and endotoxemia was investigated prospectively in 40 neurosurgical patients requiring mechanical ventilation for greater than 48 h. Each was studied up to 7 d. Swabs from the nose and oropharynx were cultured at admission, and aspirates from the stomach and trachea were cultured daily until enteral alimentation was started. Patients were evaluated every second day for endotoxemia and coagulation activation. Of 153 gastric aspirates, 66.7% contained microorganisms at a mean quantity of 10(7) cfu/ml. Nosocomial pneumonia occurred in 15 patients, septicemia in 5, and meningitis in 1. The stomach was the evident source of infection in only 1 patient with pneumonia. Of 140 plasma samples, 12 (8.6%) from 10 patients showed detectable endotoxin levels, but there was no association between endotoxemia or coagulation activation and the presence of microorganisms in the stomach. The stomach was not an important source for nosocomial infections or endotoxemia, even in patients with high gastric pH.

Adult↗
PubMed1989

Kinetics of cytomegalovirus IgG antibody following infusion of a hyperimmune globulin preparation in allogeneic marrow transplant recipients.

We investigated prospectively cytomegalovirus (CMV) IgG antibody kinetics following infusion of a CMV hyperimmune globulin preparation in 19 consecutive patients undergoing allogeneic bone marrow transplantation (BMT). CMV IgG against late antigen was measured by enzyme-linked immunosorbent assay. On a prophylactic hyperimmune globulin regimen (100 mg/kg body weight every 20 days), the mean half-life (t1/2) +/- SD of CMV IgG in seronegative patients with seronegative marrow donors was 19.7 +/- 7.9 days after the first infusion on day -7 before BMT, 24.9 +/- 12.5 days after the second infusion on day +13 after BMT, and 19.4 +/- 6.9 days after the third infusion on day +33. The t1/2 in individual patients showed a wide variation ranging from 10.9 to 47.6 days. A therapeutic high-dose hyperimmune globulin regimen (200-400 mg/kg body weight at 4-day intervals) given to five patients resulted in high serum levels of CMV IgG, which were maintained throughout therapy, even in two patients with severe intestinal graft-versus-host disease. The variation of CMV IgG kinetics between individual BMT recipients may contribute to the lack of protection from active CMV infection observed in some patients.

Adolescent↗
PubMed1988

Hematological support in patients undergoing allogenetic bone marrow transplantation.

Bone marrow transplantation is impossible without effective support with blood components during the period of pancytopenia before graft function appears. We analyzed 39 patients with leukemia and three patients with severe aplastic anemia with regard to the pre- and postgrafting requirements for RBC and PLT transfusions. Overall a median of eight RBC and four PLT concentrates were necessary in all 42 patients after allogeneic BMT (ranges, 1-32 RBC and 1-11 PLT units). Requirements were identical irrespective of the underlying disease (ALL, AML, CML, SAA). Transfusion need for RBC and PLT concentrates increased in patients over 30 years old and with a major red blood group AB0 barrier between marrow donor and recipient. The presence of grade II-IV GvHD increased RBC requirements significantly, but not PLT requirements. In addition these patients were dependent on RBC transfusions for significantly longer periods. Only one patient required therapeutic granulocyte transfusions. In a CMV-negative patient with a CMV-negative marrow donor, who died of veno-occlusive disease, cytomegalovirus was transmitted inadvertently by a seropositive PLT concentrate in his final course. Our transfusion strategy included frozen deglycerolized RBC concentrates and single donor PLT concentrates, collected mainly from the marrow donor by a cell separator. All blood products were irradiated in vitro with 1500 cGy before transfusion. An optimal transfusion policy starting before BMT can contribute to successful bone marrow transplantation.

Adolescent↗