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Biomedical subjects

H Kreis

Publications and source records attributed to H Kreis.

At least 145 records · Page 8Linked to original sources

Hepatitis B virus and hepatitis B-related viral infection in renal transplant recipients. A prospective study of 90 patients.

Hepatitis B virus (HBV) infection may induce severe hepatitis and affect long-term survival of kidney transplant recipients. Persistent viral infection has been shown to occur despite the absence of usual serologic markers. The liver and serum HBV deoxyribonucleic acid (DNA) status of 90 patients were studied prospectively; recently transplanted patients, both hepatitis B virus surface antigen (HBsAg)-positive and negative, with and without liver disease, were investigated with HBV serology, serum HBV DNA, and liver histology. Thirty-four patients had detectable HBsAg, and 21 had viral multiplication at the time of transplantation. Serial HBV DNA determinations performed in 57 of 90 patients disclosed (a) reactivation of HBV replication in 11 of 12 HBsAg-positive patients, (b) increase of viral replication when positive on the initial sample in 6 of 11 patients, and (c) development of HBV replication in 7 of 35 of the HBsAg-negative patients. Moreover, liver HBV DNA studies showed a statistical correlation between the presence of integrated liver HBV DNA and chronic hepatitis in HBsAg-negative patients. This study demonstrates prospectively the significant association of HBsAg-positive as well as HBsAg-negative HBV infection with chronic hepatitis and suggests that immunosuppressive therapy may enhance the viral replication in both HBsAg-positive and negative subjects.

Adult↗

One-month prophylactic use of OKT3 in cadaver kidney transplant recipients.

Fifty-five recipients of first cadaveric renal allografts were randomly assigned to three treatment groups in order to compare the safety and efficacy of a mouse antihuman T cell monoclonal antibody (OKT3) given prophylactically for a one-month period. This long period of administration was made possible by concomitant administration of azathioprine. The immune response against the foreign immunoglobulin was thus delayed and decreased in both intensity and severity, and OKT3 treatment could be given during almost the entire month in the majority of patients. The 18 patients who were enrolled in this treatment group had significantly (P less than 0.01) fewer rejection episodes during the first month posttransplantation than the 19 patients allocated to the high-dose (HD) steroid control group or the 18 patients allocated to the low-dose (LD) control group. Actual 2-year as well as actuarial 4-year graft survival rates were 89% in the OKT3 group, whereas they were 70% and 67% respectively in the steroid control groups. Four-year serum creatinine levels were normal and doses of steroids and other immunosuppressive agents were lower in the OKT3 group as compared with the control groups. Tolerance to OKT3 was good, and while viral infections were more frequently observed in OKT3 treated patients, the total number and the severity of infectious episodes were similar in all groups. The combination of one-month OKT3 plus azathioprine prophylaxis followed by conventional azathioprine plus low-dose steroid maintenance produced very satisfactory long-term results comparable to the best results now being obtained with cyclosporine regimens.

Adult↗

[T lymphocyte activation induced in vivo by the first injection of OKT3 monoclonal antibodies].

One of the major side effects induced by the in vivo administration of the murine monoclonal antibody OKT3 is a spontaneously reversible clinical syndrome associating in variable proportions depending on the patient: fever, chills, headaches, diarrhea and seldomly meningismus. Sera from 3 renal allograft recipients treated with OKT3 were studied and showed that a massive although transient release of some cytokines namely, Tumor Necrosis Factor alpha, Interleukin 2 and Interferon gamma is observed following the first OKT3 injection.

Antibodies, Monoclonal↗

Results of kidney transplantation at Necker Hospital.

From these data, it is possible to draw some partial conclusions: long-term therapy with ATG is only slightly better than a shorter course; OKT3 and ATG are both efficient in preventing rejection occurrences but OKT3 appears to be slightly better; given as prophylactic therapy, OKT3 induces better graft function; the combination of a 21-day course of OKT3 followed by CsA is probably detrimental to patients when compared to the combination of ATG + CsA.

Actuarial Analysis↗

Fulminant hepatitis in renal transplant recipients. The role of the delta agent.

In a series of about 300 renal transplant patients followed from 1972 to 1983, 3 cases of fulminant hepatitis were observed in HBs Ag-positive patients. In the liver biopsies of 2/3 of them, the delta antigen was detected by direct immunofluorescence with a specific anti-delta serum. This result demonstrates the responsibility of the delta agent for the development of fulminant hepatitis, and emphasizes the possibility of delta infection in HBs Ag-positive transplant patients with severe hepatitis.

Antigens, Viral↗

Toxoplasma antibody titers in renal transplant recipients. Pretransplant evaluation and posttransplant follow-up of 73 patients.

In 73 consecutive kidney transplant recipients, anti-Toxoplasma antibodies were determined before transplantation and during a 3-year follow-up after transplantation. In 9 patients, antibody titers increased significantly after transplantation. Antibody titers to various viral antigens determined in parallel remained unchanged, suggesting that the anti-Toxoplasma antibody increase was not due to polyclonal nonspecific stimulation. In 2 of the 24 pretransplant seronegative patients, acquired toxoplasmosis was diagnosed serologically after transplantation, with the observation of a strong IgM and IgG antibody response. The incidence of toxoplasmosis in this group of patients was not found to be significantly different from that in a normal population, suggesting that transmission of Toxoplasma from the transplanted kidney may not be a significant mode of contamination. Among the 49 patients who were seropositive before transplantation, reactivation of toxoplasmosis was suspected in 7 cases on the basis of a significant increase in IgG antibodies. Reactivation occurred more frequently in patients treated with azathioprine and antithymocyte globulin, and a direct relationship between administration of steroids and antibody increase was demonstrated in three patients. Although toxoplasmosis has occasionally been reported as a major infectious problem in kidney transplant recipients, our clinical and serological data show that the potential risk of developing Toxoplasma infection is low since none of the patients with either acquired or reactivated toxoplasmosis developed clinical disease.

Adolescent↗

[Complications of infections attributed to cytomegalovirus in a group of 52 kidney transplant patients].

Cytomegalovirus (CMV) infection after renal transplantation was studied over a one year period in 52 patients receiving immunosuppressive drugs. During the infectious episodes, viral shedding was systematically detected in the blood and urines by culture on MRC5 cells and CMV antibodies were titrated in the serum by ELISA (IgG: M. A. Bioproducts, IgM: immunocapture Wellcome) and compared to the initial antibody titer determined the day of transplantation. Primary CMV infection was observed in 6 of 22 seronegative patients, attested by CMV shedding from urine and/or blood and by the emergence of CMV IgM antibodies. This primary infection was severe, including at least 4 of the following features: fever greater than 38 degrees C, neutropenia, thrombocytopenia, cytolytic hepatitis, pneumonia, impaired renal function, neurological syndrome, usually occurring about 6 weeks after transplantation. Reactivation was found in 12 of 30 seropositive patients, as shown by excretion of CMV in the urine and significant rise of specific antibodies. This reactivation occurring about 9 weeks after surgery was symptomatic in 5 patients with severe illness and associated with the presence of IgM antibodies in 2 cases. Rise of CMV antibodies was observed in 10 seropositive patients without excretion of virus. It coincided with symptomatic infection in only three patients who displayed severe symptoms, with presence of CMV IgM antibodies in one case. As previously reported, we confirm that CMV infection is a frequent complication of organ transplantation. It may be clinically silent in renal transplant patients or cause problems ranging from fever to pneumonia or retinitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Preventive treatment of rejection by the prolonged administration of OKT3: decrease of the immune response of the host].

Clinical use of OKT3 for the treatment of ongoing rejection episodes has already been demonstrated as being highly effective. This work shows for the first time that combining azathioprine and OKT3 was able to delay as well as to decrease both the intensity and the quality of the anti-OKT3 immunization, allowing a 1-month prophylactic use of the MoAb. It also proves that OKT3 used prophylactically during one month can lead to 4-year first cadaver graft and patient survival rates better than those ever reported with any other immunosuppressive regimen. These results were obtained with lower doses of steroids and other immunosuppressive agents than in conventionally treated control patients. After the first two injections of OKT3, tolerance was perfect allowing out-hospital administration, and side effects consisted only in an increased number of viral infections instead of the bacterial infections observed in the conventional treatment groups. The prophylactic use of OKT3 should give even better results if it were possible to reach a 1-month administration schedule in all patients by modulating the dose of OKT3 according to the T3+ cell count and the monitoring of serum OKT3 levels.

Antibodies, Monoclonal↗

Restriction of the human in vivo immune response against the mouse monoclonal antibody OKT3.

The murine monoclonal antibody OKT3 (IgG2a) was administered prophylactically to 17 renal allograft recipients (5 mg/day, i.v.), either alone or in association with corticosteroids (0.25 mg/kg/day) and azathioprine (3 mg/kg/day). In all patients the kinetics of the IgM and IgG anti-OKT3 response was monitored by means of immunofluorescence and ELISA. All patients treated with OKT3 alone showed a rapid and strong sensitization that completely neutralized the therapeutic effectiveness of the monoclonal antibody. The anti-OKT3 sensitization was manifested by accelerated OKT3 clearance and abrupt reappearance of circulating OKT3+ cells before the end of treatment. This immune response was significantly delayed and reduced in its incidence and intensity in patients receiving low dose corticosteroids and azathioprine in association to OKT3; mainly IgM anti-OKT3 antibodies that did not accelerate OKT3 clearance were then observed. The fine specificity of the antibodies produced was studied, using patients whole sera and various mouse IgG2a-affinity chromatography-purified serum fractions. The results obtained showed that the anti-OKT3 response was remarkably restricted to two main categories of antibodies: a) anti-idiotypic antibodies that inhibited OKT3 binding to T cells and abrogated its therapeutic activity and b) anti-mouse IgG2a (anti-isotypic) antibodies that did not neutralize OKT3 immunosuppressive activity. These results suggest that OKT3-immunized patients might still be sensitive to the immunosuppressive effect of other anti-T cell monoclonals that do not share the OKT3 idiotype and possibly isotype.

Animals↗

Evaluation of allograft perfusion by radionuclide first-pass study in renal failure following renal transplantation.

To assess the diagnostic value of indices measured on a first-pass curve, we performed 72 radionuclide renal first-pass studies (RFP) in 21 patients during the early weeks following renal allograft transplantation. The diagnosis was based on standard clinical and biochemical data and on fine needle aspiration biopsy (FNAB) of the transplant. Aortic and renal first-pass curves were filtered using a true low-pass filter and five different indices of renal perfusion were computed, using formulae from the literature. Statistical analysis performed on the aortic and renal indices indicated excellent reproducibility of the isotopic study. Although renal indices presented a rather large scatter, they all discriminated well between normal and rejection. Three indices have a particularly good diagnostic value. In the discrimination between rejection and Acute Tubular Necrosis (ATN), only one index gave satisfying results. The indices, however, indicate that there are probably ATN with an alternation of renal perfusion and rejection episodes where perfusion is almost intact. We conclude that radionuclide first-pass study allows accurate and reproducible quantitation of renal allograft perfusion. The measured parameters are helpful to followup the course of a post-transplantation renal failure episode and to gain more insight into renal ischemia following transplantation.

Acute Kidney Injury↗