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Biomedical subjects

R Pichlmayr

Publications and source records attributed to R Pichlmayr.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Comprehensive range of services for general hospitals in the area of organ donation nearly doubles the number of donors in 2 years with a simultaneously economical process].

To overcome the donor shortage, any potential donor resource must be detected. By establishing a professional service for peripheral hospitals, the numbers of donors available in small hospitals could be nearly doubled: 85% of all donors in our region come from nonuniversity hospitals. By using total quality management techniques, the time requirements for organ donation after confirmation of brain-death and given consent could be reduced to 6 h.

Cost-Benefit Analysis↗
PubMed1997

[The efficacy dilemma].

Effectivity and efficiency of medical treatment have conflicting aims which result in a conflict of interests between a patient, interested in maximal effectively and the society, interested in maximal efficiency. The physician cannot solve this conflict because he is primarily obliged to the interests of the individual patient. If rationing is unavoidable in modern health care services, there must be an open discussion in order to reach a broad consensus within the society.

Abdominal Neoplasms↗
PubMed1997

[Analysis of prolonged intensive care after abdominal surgery interventions with special reference to quality of life and economy].

In a retrospective study of 62 surgical patients with at least 30 days of intensive care, a hospital mortality rate of 40.3% with a median survival time of 3.7 years for the discharged patients (n = 37) was found. The median gastrointestinal quality of life Index (GLQI) for the surviving patients was 104 points, and overall 56 quality-adjusted life years (QALYs) were obtained, resulting in costs of 68,250 DM per QALY. Although intensive care is one of the most expensive treatment modalities in the health system, economic aspects should not be the cause for withdrawing or withholding intensive therapy.

Adult↗
PubMed1996

Fibrosis in chronic rejection of human liver allografts: expression patterns of transforming growth factor-TGFbeta1 and TGF-beta3.

Activation and transformation of lipocytes (Ito cells, stellate cells) into alpha-actin-positive myofibroblast-like cells is an essential step in the initiation of liver fibrosis. Transforming growth factor-beta (TGF-beta) is considered an important mediator of this process. In order to determine mechanisms of fibrotic deposition in a hepatic transplant setting, we analyzed 10 chronically rejected human liver allografts for the expression of extracellular matrix (ECM) molecules, myofibroblast-like cells (alpha-actin), macrophages, and TGF-beta1 and -beta3. Using single- and double-immunohistochemical staining techniques, all specimens investigated showed increased deposition of the ECM proteins fibronectin, tenascin, undulin, and collagen VI with a characteristic densification especially in pericentral areas. Likewise, strong accumulation of alpha-actin-positive cells and TGF-beta1-expressing macrophages was observed in the same fields, supporting the concept of lipocyte activation/transformation and subsequent ECM production fostered by macrophage-derived TGF-beta1. In contrast, TGF-beta3 was found to be mainly expressed by a markedly increased number of lipocytes. Interestingly, distribution of TGF-beta3 corresponded to that of tenascin, an ECM molecule known to be involved in early matrix organization, suggesting that TGF-beta3 may likewise act mainly in early stages of fibrogenesis. Furthermore, TGF-beta3 restriction to high numbers of a single cell type (i.e., lipocytes) implied a possible role in cell proliferation through autocrine loops. In conclusion, fibrosis in chronic rejection seems to follow similar mechanisms as in non-transplanted livers but additionally suggests differential temporal and functional roles for the TGF-beta isoforms 1 and 3 in the course of a multistep process leading to lipocyte transformation and ECM production.

Actins↗
PubMed1996

The long-term course of hepatitis C after kidney transplantation.

Patients with chronic hepatitis run the risk of developing progressive liver disease during immunosuppressive therapy after kidney transplantation. To determine the impact of chronic hepatitis C on morbidity and mortality we analyzed 162 anti-HCV positive of 1241 renal-grafted patients (prevalence 13.1%; 84.9% HCV RNA positive) regularly surveyed in our outpatient clinic between 1992 and 1994. The mean age at transplantation was 44.5 (6-69) years, and follow-up after grafting was 7.4 (0.1-23.9) years. The immunosuppressive regimen and frequency of rejection episodes in HCV-infected patients were comparable to the total population. Only 4.3% (5/117) of the anti-HCV positive, HBV negative patients living with functioning grafts developed a markedly compromised liver function. Fifteen (9.3%) of the HCV-infected patients died, but none suffered from posthepatitic cirrhosis. An additional retrospective analysis of causes of death after transplantation prior to 1992 revealed that liver disease had only been responsible for 2% of the deaths (7 of 324) in the HBsAg negative population (n= 1901). In contrast, the predominant cause of death in the HBsAg positive population (n=76) was posthepatitic cirrhosis in 58% (15 of 26). Thus, kidney transplantation in patients with replicative hepatitis C and normal liver function appears to be justified because of low early and late morbidity and mortality due to chronic liver disease. HBV infection and hemosiderosis substantially increase the risk of chronic liver disease in renal transplant recipients with hepatitis C.

Adolescent↗
PubMed1996

A new oral formulation of cyclosporine for early oral immunosuppressive therapy in liver transplant recipients.

CsA-ME is a new oral microemulsion formulation of CsA. Studies in stable liver grafted patients with cholestasis and subsequent poor absorption of the conventional cyclosporine formulation showed a substantial increase in CsA absorption after conversion to CsA-ME. To investigate its use in patients during the early course after liver transplantation we recruited 50 liver transplant recipients in two centers. During the first study phase A CsA-ME was administered to 20 patients in incremental doses after a short initial course of intravenous cyclosporine. During the second study phase B (30 patients) CsA-ME was administered from the time of transplantation. One year actual patient and graft survival of patients included in phase A and B of the trial was between 90% and 93.3%; 50% and 60% of the patients enrolled in phase A and phase B of the trial were free from rejection at month 3, respectively. Chronic rejection was diagnosed in one patient. No increase in the incidence of CsA related side effects was observed. The optimum CsA-ME starting dose was found to be 10 mg/kgbw/day for patients without external biliary diversion and 15 mg/kgbw/day for patients with a T tube in situ. Using these starting doses, 26 consecutive patients with external bile diversion via T tube were treated with CsA-ME from the day of transplantation. Intravenous CsA was necessary only in three patients. When CsA-ME absorption in patients with stable liver function was compared with that in patients with early liver dysfunction, no difference in the pharmacokinetic profiles was observed between the groups. Our results indicate that CsA-ME therapy is effective and well tolerated in liver graft recipients, even in patients with external biliary diversion during the early posttransplant phase. Thus, CsA-ME is a useful alternative to intravenous CsA treatment in these patients.

Administration, Oral↗
PubMed1996

Liver transplantation in children with chronic end stage liver disease: factors influencing survival after transplantation.

To identify pretransplant factors that are influencing survival after orthotopic liver transplantation a Cox proportional hazards regression model was applied to 118 children with chronic terminal liver failure transplanted at Medical School Hannover during the period of 1978 to 1994. The response variable was survival, as covariates a total of 19 pretransplant variables were entered--i.e. age, diagnosis (biliary cirrhosis, metabolic cirrhosis, postnecrotic cirrhosis, cryptogenetic cirrhosis) sex, laparotomy prior to OLT, height, weight, standard deviation scores for height and weight, date of first OLT, serum alanine aminotransferase, asparagine aminotransferase, albumin, total bilirubin, cholinesterase activity, glomerular filtration rate, and prothrombin time. Significant independent predictors of survival after OLT were bilirubin (P=0.0024), SDS for weight (P=0.034), and albumin (P=0.039). In a subsequent discriminant analysis cut off points for these variables could be identified--i.e., bilirubin >340 micromol/L, SDS for weight <-2.2 and albumin < 33 g/L. Patients with one or more of these risk factors were grouped as urgent indication group (n=76) and those with no risk factor as elective indication group (n=42). Comparing the posttransplantation survival in these groups there is a statistically significant difference at 1 year (57% vs. 90.5%) and 4 years (49% vs. 90.5%) after OLT (P=0.0001, log rank test). It is concluded that the risk of OLT is much higher if liver function is very poor. Optimal nutritional support prior to transplantation is mandatory to optimise the clinical status of the children and to improve the results of OLT.

Adolescent↗
PubMed1996

Incidence of Pneumocystis carinii pneumonia after renal transplantation. Impact of immunosuppression.

The incidence and potential risk factors of Pneumocystis carinii pneumonia (PCP) in our population of renal transplant recipients were analyzed retrospectively. Of 1427 patients who received transplants between January 1986 and June 1994, 1192 were evaluated. Four different immunosuppressive regimens were applied: (1) cyclosporine (CsA) + prednisolone (Pred), (2) CsA + azathioprine (Aza, 2 mg/kg/day) + Pred, (3) CsA + Aza + antithymocyte globulin, and (4) (after December 1, 1993, European multicenter trial) FK506 + Aza (1 mg/kg/day) + Pred. No prophylaxis against PCP was performed. Before December 1, 1993, three PCPs in 494 patients on protocol 2 or 3 occurred (0.6%). Afterward, seven PCPs in 77 patients occurred (9%): three in 38 patients on protocol 2 (7.8%) and four in 28 patients on protocol 4 (14.3%). Comparing patients with PCP on CsA and FK506, the mean Aza dose was 2.40 and 1.32 mg/kg/day, five and two patients received additional steroids, antibody treatment was used in three and no patients, and CMV infections occurred in five and two patients, respectively. The incidence of PCP with a moderate CsA-based immunosuppressive regimen is low and seems to occur only in cases of additional immunosuppressive cofactors. Despite a general increase of PCP, its incidence was highest in patients on FK506 with fewer immunosuppressive cofactors. Thus, prophylaxis against PCP after renal transplantation should be performed, if not in every renal transplant recipient, at least in case of treatment with additional steroids, antibodies, or FK506.

Adult↗
PubMed1996

[Rehabilitation of children and adolescents after organ transplantation].

Today transplantation of different vital organs is an often and successfully applied clinical method. After organ transplantation the degree of recovery mainly depends on graft function. Besides social, work and school reintegration as well as the development of independence and self-responsibility are decisive for a general recovery. Therefore a rehabilitation should be planned in the scope of the medical care after transplantation. For this reason the rehabilitation center for children and juvenile was founded in Stronach, Austria in 1992. Since then until March 1995 136 kidney- and 54 liver transplanted patients have been treated. There is a significant increase of hemoglobine in all cases and a significant decrease of creatinine as a parameter of graft function in kidney-transplanted patients. By spiroergometric testing the heartrate at the aerobic-anaerobic threshold can be easily estimated in children and juvenile and in consideration of these results the physical endurance can be distinctively increased by an individual training program.

Adolescent↗
PubMed1996

How best to use tacrolimus (FK506) for treatment of steroid- and OKT3-resistant rejection after renal transplantation.

Nineteen patients with biopsy-confirmed ongoing acute rejection of renal allografts were converted from standard immunosuppression to FK506. Eight grafts showed vascular rejection and 11 had cellular rejection on biopsy. All patients had already received intravenous high-dose steroid treatment. Ten patients also had additional OKT3 rescue therapy. Initial FK506 doses were 0.13 +/- 0.06 mg/kg/day; the FK506 whole blood trough level after 3 days of treatment was 9.3 +/- 4.5 ng/ml. After conversion to FK506 all but four patients also received azathioprine, 1.5-2 mg/kg/day, and all patients received oral prednisolone. Concomitant with initiation of FK506, an anti-infective prophylaxis was prescribed, consisting of ganciclovir and trimethoprim/sulfamethoxazole. Sixteen out of 19 of the grafts (84%) were rescued successfully, including two grafts of patients already on hemodialysis at the time of conversion. Graft function of the responders improved from an average serum creatinine level of 364 +/- 109 mumol/L to 154 +/- 49 mumol/L. Of the patients receiving high-dose steroids alone prior to FK506 initiation, 8/9 responded to FK506 treatment, compared with 8/10 of those who had also received OKT3. During the mean follow-up of 35 weeks after conversion, no clinically apparent cytomegalovirus infection and no pneumonia were seen. Treatment with FK506 may successfully suppress ongoing acute rejection, even if antilymphocyte preparations have failed. FK506 can be used at a lower dose than so far recommended without impairing the antirejection potential. An additional anti-infective prophylaxis seems effective in preventing severe complications in the first months after rejection therapy.

Adult↗
PubMed1996

Immunoprophylaxis with a monoclonal anti-IL-2 receptor antibody in liver transplant patients.

The immunosuppressive effect of a monoclonal antibody (moAb), BT563, directed to the alpha-chain of the IL-2R (CD25), was analyzed in a prospective nonrandomized trial and a prospective randomized trial. Primary objectives were evaluation of the incidence of acute rejections and infections; secondary objectives were safety and tolerability of the moAb. A total of 28 patients were enrolled (phase II) to receive 10 mg/day of BT563 (12 days) as immunoprophylaxis in combination with cyclosporine, azathioprine, and low-dose steroids. Subsequently 32 patients were randomly assigned (phase III) to receive BT563 (10 mg/day) for 12 days or ATG (5 mg/kg/day) for 7 days in addition to cyclosporine and low-dose steroids. No side effects of the BT563 treatment were noted. The actuarial survival was 82% at 12 months in the phase II trial and 92% at 12 months in both arms of the phase III trial. There was one acute rejection in the phase II trial. No acute rejections were noted in the BT arm of the phase III trial and 5 acute rejections were treated in the ATG arm. In the phase II trial 7 infectious episodes were observed, while one infection was seen in the BT arm and 7 in the ATG arm of the triple immunosuppression phase III trial. In all patients circulation of coated CD25+ lymphocytes was observed during BT563 treatment; there was no evidence of depletion or modulation of CD25+ cells. Mean serum levels of BT563 ranged from 1.6 to 7.6 microgram/ml throughout the therapy. An antimurine response was seen in 82% (phase II) and 100% (phase III) of the patients. Antirabbit antibodies were found in 56% of the patients treated with ATG. Analysis of the antimurine response specificity revealed in 56% blocking anti-isotypic antibodies and only in 3% of the patients an anti-idiotypic response. The data of the study presented suggest that therapy with an anti IL-2R moAb is at least equal to ATG application according to the incidence of acute rejections and infections.

Acute Disease↗
PubMed1996

Development, stability, and clinical correlations of allogeneic microchimerism after solid organ transplantation.

To assess the development, stability, and clinical relevance of donor-type microchimerism, skin and blood were analyzed in heart (n = 53) and liver (n = 18) transplant recipients by nested polymerase chain reaction. Microchimerism was detectable in 40 (75%) and 13 (72%) patients after heart and liver transplantation, respectively. In heart transplantation, chimerism-positive patients showed a lower frequency of acute rejection as compared with negative patients, although this was only of borderline statistical significance. Repeated intraindividual analyses demonstrated variable patterns of microchimerism over time, but changes did not correlate to the clinical state. In liver transplantation, chimeric state showed no clear correlation with the patients' immunological situation. Our results demonstrate that peripheral microchimerism frequently develops after different types of organ transplantation and represents a dynamic process but without diagnostic value to predict the immunological risk for individual patients.

Base Sequence↗
PubMed1996

Biliary malignancies in primary sclerosing cholangitis: timing for liver transplantation.

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease associated in 10% to 36% of those with hepatobiliary malignancies, which are, in the majority of cases, not known prior to transplantation. Diagnosis of carcinomas in a PSC setting at an early stage has not yet been achieved, because there are no differences in the age of patients or clinical course, particularly with regard to the time between diagnosis of PSC and detection of carcinomas. To assess optimal timing for transplantation in patients with PSC, we applied the Mayo survival model to 48 patients receiving transplants for that disease in our center between 1972 and 1994. Of these patients, 10 had a biliary malignancy, which was incidental in 9. According to the Mayo model, low-, moderate-, and high-risk groups of patients could be formed. The actuarial patient survivals at 1 and 7 years were 100% and 100% (low risk), 68.6% and 68.6% (moderate risk), and 54.6% and 46.8% (high risk), respectively. Patients with a biliary malignancy had a 30% survival at 1 year; none survived 6 years. Local recurrence of the tumor was found in 3 patients, 2 of them with low tumor stages at the time of transplantation. Analysis of the Mayo Model risk scores demonstrated a marked increase in the incidence of biliary malignancies at a score above 4.4. All patients with tumors were found to have a score above 4. Moreover, the prevalence rate rose from 14.3% in the low-risk group to 33.3% in the moderate-risk group. There was no difference in the clinical courses at 6 to 12 months prior to transplantation; in particular, the bilirubin levels (PSC alone, 250 +/- 230 mumol/L; PSC with carcinoma, 288 +/- 182 mumol/L) did not differ significantly (P > .05) between both patient groups. Because the outcome after transplantation is poor even in patients with low-grade malignancies, early timing of transplantation in patients with PSC is suggested to prevent formation of biliary malignancies. Therefore, regular scoring of patients with the Mayo Model risk score is suggested, and transplantation should be taken into consideration at scores above 4.

Actuarial Analysis↗
PubMed1996

Hepatitis B virus mutations in the pre-S genome before and after liver transplantation.

Mutational changes in the pre-S region of hepatitis B virus (HBV) were analyzed in 20 patients who experienced HBV reinfection after orthotopic liver transplantation (OLT). HBV DNA was extracted from patient sera before and after OLT. The pre-S sequence was amplified via polymerase chain reaction, subcloned, sequenced, and analyzed. In 18 of 20 patients, mutational changes were found in the pre-S region pre- or post- OLT; 11 showed point mutations (1-10) and 7 cases major changes (insertions/deletions). For the point mutations, there was no trend in the selection of wild-type (wt) HBV before or after OLT in the pre-S region. Additional HBV reinfection during hepatitis B surface antigen antibody (anti-HBS) administration had no influence on selection pressure in the pre-S region. In contrast, insertions/deletions were more frequently found before OLT. In the 7 patients with deletions/insertions, changes in the hepatocyte attachment site were not seen after OLT. Interestingly, the only patient with changes in a major virus population after OLT had changes in the CCAAT-box of the S-promoter. As shown by gel shift analysis, this mutation was associated with loss of specific binding to this element and thus probably led to dysregulation of S-gene transcription. Major changes in the pre-S genome are mainly seen before OLT, and HBV reinfection does occur with the intact hepatocyte attachment sites after OLT. Anti-HBs (hepatitis B immune globulin [HBIg]) creates no selection pressure on the pre-S region. The mutation in the CCAAT-box of the S-promoter potentially leads to its dysregulation and may be associated with the occurrence of fibrosing cholestatic hepatitis after OLT.

Adult↗
PubMed1996

Famciclovir treatment of hepatitis B virus recurrence after liver transplantation: a pilot study.

Despite hepatitis B immunoprophylaxis hepatitis B virus (HBV) recurrence is a frequent and often fatal complication after orthotopic liver transplantation (OLT). The purine nucleoside analogues penciclovir and its oral form famciclovir (FCV) proved to be well tolerated and effective against herpes simplex and zoster virus infections. In addition, an effective reduction of duck and human HBV replication was observed. Therefore, we conducted an uncontrolled pilot study of famciclovir in patients with HBV recurrence after OLT. Twelve patients have received famciclovir for at least 3 months in an open compassionate-use protocol. FCV was administered orally 500 mg three times a day for all patients (except one patient who was started on 750 mg three times a day for the first 2 weeks). Immediately after starting famciclovir, serum HBV DNA levels declined in 9 of 12 patients (75%) with a mean reduction from baseline levels of 80% after 3 months, 90% after 6 months, and > 95% after 12 months of treatment. With continued treatment, 5 of these 9 patients became negative by conventional hybridization assay, and in one of these HBV DNA became undetectable by polymerase chain reaction (PCR) 28 weeks after the start of treatment. Three patients showed no (sustained) reduction in HBV DNA after at least 3 months of treatment; therefore, FCV was stopped. Latest serum alanine aminotransferase (ALT) levels decreased in 6 of 12 patients (50%) with a median decrease of 80% (range, 40%-95%) in comparison to pretreatment ALT values. ALT levels normalized in 4 patients (33%). One patient died due to sepsis and peritonitis in week 13 of treatment. This event was not related to FCV. No clinically significant side effects were noticed in any patient. The oral nucleoside analog famciclovir reduces HBV replication and transaminase levels in patients with HBV recurrence after liver transplantation. Because long-term FCV treatment is well tolerated, famciclovir appears to be a promising antiviral strategy in the treatment of HBV in immunocompromised patients.

2-Aminopurine↗
PubMed1996

Retroperitoneal placement of living related adult renal grafts in children less than 5 years of age--a feasible technique?

The extraperitoneal approach was used for transplantation of adult renal grafts in eight children under 5 years, three of them weighing less than 10 kg. Usually, children of this size are approached transperitoneally. The modified procedure included partial mobilization of the right liver to provide enough space for retroperitoneal graft placement and positioning of the vascular anastomoses, invariably to the aorta and caval vein. With this regimen, no significant space problems were encountered in recipients as small as 9 kg, and particularly, neither arterial nor venous complications occurred. Currently, at a mean follow-up of 2.4 years, all patients are alive with well-functioning grafts. Thus, the extraperitoneal approach represents a feasible and successful procedure in the pediatric living related renal transplantation setting for recipients under 10 kg of weight.

Adult↗
PubMed1996

Two-year data from the European multicentre tacrolimus (FK506) liver study.

To provide a more definitive assessment of the efficacy and safety of tacrolimus therapy in comparison with cyclosporin, the extended follow-up of the European multicentre study is reported. Two-year Kaplan-Meier estimates indicated significant reductions in acute (tacrolimus 45.4%, cyclosporin 55.8%; P = 0.006), refractory (1.2% versus 6.4%; P = 0.003) and chronic rejection (2.0% versus 6.9%; P = 0.015) despite significantly lower steroid usage in patients receiving tacrolimus therapy. Patient and graft survival rates (80.6% versus 74.8% and 74.5% versus 70.0%, respectively) were also superior, although these failed to reach statistical significance. Safety profiles were comparable for most major categories (including renal, neurological and glucose metabolic disorders) and in certain aspects were more favourable for tacrolimus. Hypertension (28.0% versus 39.6%, P < 0.01) and cytomegalovirus infection (14.8% versus 22.3%, P < 0.01), two events with important long-term clinical consequences, were reported significantly less frequently. Hirsutism (0.0% versus 8.7%, P < 0.01) and gum hyperplasia (0.0% versus 2.3%, P < 0.05) were absent in patients receiving tacrolimus. Tacrolimus appears to provide effective and safe long-term immunosuppression.

Adolescent↗