Search PubMed⌕ Search

Biomedical subjects

T Philipp

Publications and source records attributed to T Philipp.

At least 127 records · Page 7Linked to original sources
PubMed1997

Results of cardiac operations in five kidney transplant patients.

Because of the paucity of literature reports about cardiac operations in renal-transplant patients we performed a retrospective study encompassing all such patients operated upon in our institution in 1993 and 1994. During this time 5 renal transplant patients underwent cardiac surgical procedures between 1 and 9 years after transplantation: in 4 patients coronary artery bypass grafting (CABG) was carried out and in one patient aortic valve replacement. We analyzed pre-, peri-, and postoperative data. Late results were obtained by questionnaire from the patients' primary physicians. Short- and long-term results were excellent. Mortality was 0%. At late follow-up (8-23 months) all patients were in NYHA class II or better. Postoperatively all patients experienced a clear improvement of their cardiac symptoms. None of the transplanted kidneys deteriorated. One patient who had to undergo intermittent hemodialysis preoperatively improved so much that she did not require any dialysis postoperatively. Although the total number of patients in this study is limited we believe it can be stated that renal transplant patients can undergo cardiac operations with generally good results.

Adult↗
PubMed1997

GBV-C/HGV infection in renal dialysis and transplant patients.

BACKGROUND: Recently a new human virus (GBV-C/HGV) was identified. With the use of the polymerase chain reaction (PCR) the possibility of a high prevalence of the GBV-C/HGV infection in haemodialysis patients was demonstrated. The aim of the present study was to use a combination of the PCR and a new diagnostic test for antibodies to the viral envelope protein E2 to assess the prevalence of the GBV-C/HGV infection in German patients with renal failure. METHODS: RT-PCR and ELISA were used to detect GBV-C/HGV RNA and antiviral antibodies (anti-E2) in the sera of 31 patients on a maintenance haemodialysis (HD)), 25 patients on a perioneal dyalisis (CAPD), and 92 renal transplant patients (RT). RESULTS: A statistical trend was noted for a higher rate of the GBV-C/HGV RNA in the whole group of patients with renal failure (11.5%) than in the control group of organ donors (5.5%); The difference between GBV-C/HGV RNA prevalence in RT patients (15.2%) and in organ donors (5.5%) was found to be significant. Anti-E2, which are considered as an indicator of a past GBV-C/HGV infection, were detected in 12.9% of HD patients, in 20.0% of CAPD patients, in 10.9% of RT patients, in 11.1% of organ donors, and in 10.9% of blood donors. These differences were not significant. Time on haemodialysis was significantly longer in GBV-C/HGV infected patients compared to uninfected patients and all patients with the GBV-C/HGV RNA have a history of blood transfusions. CONCLUSIONS: Patients with renal failure treated with dialysis or subjected to renal transplantation are at increased risk of aquiring the GBV-C/HGV infection. Higher rates of the GBV-C/HGV RNA and a similar prevalence of anti-E2 in patients with renal failure as compared to donors suggest that the rate of GBV-C/HGV infection resolution in immunosuppressed patients with renal failure might be lower than in immunocompetent patients.

Adult↗
PubMed1997

Cardiac surgery in patients with end-stage renal failure.

End-stage renal failure is commonly considered a significant factor for an increased risk after coronary artery bypass grafting. This holds true for patients who have received a kidney transplant (NTX group) as well as for patients who require chronic hemodialysis (HD group). To assess the risk in our population we performed a retrospective analysis of 22 patients with end-stage renal failure (HD group: 17, NTX group: 5) who underwent cardiac surgery. The perioperative course was compared to a normal population. In addition to standard data we assessed the following factors: renal failure etiology, risk factors, concurrent diseases, duration of renal failure, function of renal graft, ECG (paying special attention to signs of previous myocardial infarctions and rhythm disorders), results of cardiac catheterization and coronary angiography, NYHA class and urgency of operative intervention. Complications and mortality were the main measures of the perioperative course. We analyzed the hospital charts retrospectively and requested the patients' physicians to complete a questionnaire about the patient's present condition. All HD group patients were dialyzed on the day before surgery. The first postoperative HD was performed for hyperkalemia or signs of volume overload (pulmonary capillary wedge pressure > 20 mmHg) when signs of pulmonary function deterioration were seen. HD was successful in treating these conditions. 3 of the 17 patients on HD expired postoperatively, 4 died within 3 years, all of unrelated diseases. Mortality and morbidity was 0% in the NTX group. In one NTX patient who required intermittent HD preoperatively because of poor renal graft function, renal function improved postoperatively, presumably secondary to better renal perfusion, and he did not require HD after his cardiac surgery. By surgical intervention the NYHA class of all patients improved (by 1.6 on the average) as well as their quality of life. Because of these good short- and long-term results and relatively low operative risk we support an approach of prompt work-up and surgical intervention when necessary in HD and NTX patients.

Adult↗
PubMed1996

Effects of noradrenaline and neuropeptide Y on rat mesenteric microvessel contraction.

We have studied the contractile effects of the sympathetic transmitter noradrenaline and its cotransmitter neuropeptide Y (NPY) given alone and in combination on isolated rat mesenteric resistance vessels (200-300 microns diameter). Noradrenaline and NPY each concentration-dependently contracted rat mesenteric microvessels (EC50 approximately equal to 800 nM and 10 nM, respectively), but noradrenaline caused considerably greater maximal effects than NPY (14.3 mN vs. 3.5 mN). A low antagonistic potency of yohimbine indicated that the response to noradrenaline did not involve alpha 2-adrenoceptors, and the subtype-selective antagonists 5-methylurapidil, tamsulosin and chloroethylclonidine indicated mediation via an alpha 1A-adrenoceptor. Shallow Schild regressions for prazosin and 5-methylurapidil indicated that an alpha 1-adrenoceptor subtype with relatively low prazosin affinity might additionally be involved. Studies with the NPY analogues PYY, [Leu31, Pro34] NPY and NPY18-36 demonstrated that NPY acted via a Y1 NPY receptor. In addition to its direct vasoconstricting effects NPY also lowered the noradrenaline EC50 but did not appreciably affect maximal noradrenaline responses indicating possible potentiation. The potentiating NPY response occurred with similar agonist potency as the direct contractile NPY effects and also via a Y1 NPY receptor. The Ca2+ entry blocker nitrendipine (300 nM) reduced direct contractile responses to noradrenaline and NPY but did not affect the potentiation response to NPY.

Animals↗
PubMed1996

Infection-associated cellular activation accelerates chronic renal allograft rejection in rats.

The etiology of chronic rejection is unknown, although acute rejection, viral infection, and initial graft ischemia have been implicated. To test the effects of infections on the process of chronic rejection, we simulated bacterial infection by the administration of the endotoxin lipopolysaccharide (LPS), a potent activator of various cell types in an established rat model of chronic rejection. Lewis recipients of Fisher 344 kidneys were treated with a single dose of LPS or vehicle 8 weeks following transplantation and grafts were examined at various time points. In the chronically rejecting controls, leukocytic infiltration and the expression of cytokines peaked at 16 weeks. In LPS-treated hosts, leukocyte infiltration and cytokine expression peaked at 12 weeks. By 16 weeks, glomeruli in LPS-treated recipients had become far more sclerotic than those in controls, mimicking the changes observed in controls at 24 weeks. We conclude that infections may play an important role in the development of chronic rejection.

Animals↗
PubMed1996

Mycophenolate mofetil inhibits lymphocyte binding and the upregulation of adhesion molecules in acute rejection of rat kidney allografts.

Mycophenolate mofetil (MMF) interacts with purine metabolism and possibly with the expression of adhesion molecules. In the present study, we analysed the expression of these molecules in transplanted kidney allografts treated with RS LBNF1 kidneys were orthotopically transplanted into Lewis rats and either treated with RS (20 mg/kg/day) or vehicle. Rats were harvested 3, 5 and 7 days following transplantation. For binding studies, fresh-frozen sections of transplanted kidneys were incubated with lymph node lymphocytes (LNL) derived from transplanted rats. Additionally, immunohistology was performed with various monoclonal antibodies. In general, MMF resulted in better preservation of graft structure by 7 days. Cellular infiltration and tubular atrophy were less pronounced. At day 3, macrophages were diminished in MMF-treated animals to a high extent, while the number of T cells was almost identical to that of controls. In addition, the number of cells positive for MHC class II and LFA-1 was reduced in the MMF-treated animals. These findings correlated with the binding results. Three days following engraftment, LNL bound to MMF-treated kidneys to a lesser extent compared to controls. In conclusion, MMF resulted in a markedly reduced leucocytic infiltrate, presumably based on a reduced expression of lymphocytic adhesion molecules and an interaction with macrophages.

Animals↗
PubMed1996

Diltiazem minimizes tubular damage due to FK506-mediated nephrotoxicity following ischemia and reperfusion in rats.

We examined the nephrotoxicity of tacrolimus (FK506) in a model of mild warm ischemia. After clamping of both renal arteries of male Sprague-Dawley rats for 20 min, the animals received tacrolimus (3 mg/kg/day i.p.), vehicle of a combination of tacrolimus (3 mg/kg/day i.p.) and diltiazem (12 mg/kg, orally) or vehicle and diltiazem (12 mg/kg, orally). The excretion of urinary enzymes was determined on a daily basis, creatinine clearance at day 10. Tacrolimus significantly increased NAG (N-acetyl-beta-glucosaminidase) excretion and associated histological damage, finally decreasing creatinine clearance. The toxic potential of tacrolimus was markedly enhanced by ischemia. The additional application of diltiazem reduced NAG excretion and histological damage without affecting creatinine clearance. Thus, the protective effect of diltiazem on tacrolimus-induced nephrotoxicity seems to be at least partially a tubular one.

Acetylglucosaminidase↗
PubMed1996

Initial experience with tacrolimus rescue therapy in OKT3 resistant rejection.

Follow-up of 9 renal transplant recipients who were converted from cyclosporin A to tacrolimus (FK506) as recue therapy for intractable rejection is described. All patients initially received a cyclosporin A based immunosuppression. They developed biopsy proven acute rejections 22 +/- 11 days after transplantation which did not resolve by i.v. steroids and subsequent OKT3. Fifty-three +/- 11 days post transplantation the patients were converted from cyclosporin A to tacrolimus. After conversion to tacrolimus 6 patients developed a stabile transplant function. One transplant recipient who initially responded to tacrolimus lost his graft due to a chronic rejection 9 months following conversion. Two patients with never functioning kidneys remained on dialysis despite tacrolimus therapy. After conversion no serious adverse events occurred and only a slightly increased infection rate and hyperglycemia were noted as major side effects of tacrolimus. Tacrolimus rescue therapy was effective in treating acute renal allograft rejection unresponsive to steroids and OKT3. Tacrolimus rescue therapy was not accompanied by a substantial rise in complications. Patients with never functioning kidneys did not seem to benefit from tacrolimus rescue therapy.

Adult↗
PubMed1996

Effects of mycophenolic acid mofetil on acute rejection of kidney allografts in rats.

Mycophenolic acid mofetil (MMF) is an agent which has recently gained a lot of attention. In clinical trials MMF has reduced the rate of acute rejection episodes in human recipients of kidney allografts by inhibiting inosin-monophosphat-dehydrogenasis (IMPDH), an enzyme involved in the purin metabolism and related to the expression of adhesion molecules. The aim of the present study was to analyze the effects of MMF upon the expression of adhesion molecules in transplanted kidney allografts. LBNF1 kidneys were orthotopically transplanted into Lewis rats and either treated with MMF (20 mg/kg/day) or vehicle. Rats were harvested 3, 5 and 7 days following transplantation. Immunohistology was performed with various monoclonal antibodies. In general, MMF resulted in a better preservation of graft structure by 7 days. Cellular infiltration and tubular atrophy were less pronounced. At day 3, macrophages were diminished in MMF-treated animals to a high extent, while the number of T-cells was almost identical as compared to controls. In addition, the number of cells positive for MHC class II and LFA-1 was reduced in the MMF-treated animals. In conclusion, MMF resulted in a markedly reduced leukocyte infiltrate, presumably based on a reduced expression of lymphocytic adhesion molecules and an interaction with macrophages.

Animals↗
PubMed1996

Infections and reduced functioning kidney mass induce chronic rejection in rat kidney allografts.

The etiology of chronic rejection of kidney allografts is unknown, although hyperfiltration, acute rejection, viral infection and initial graft ischemia have been implicated. To test whether endothelial activation may be the link between these factors and chronic rejection, the endotoxin (lipopolysaccharide-LPS), a potent activator of endothelial cells, was evaluated in an established chronic rejection model. Bilaterally nephrectomized Lewis recipients of orthotopically transplanted Fisher 344 kidneys were treated briefly with low dose cyclosporine (1.5 mg/kg/day x 10). Recipients were given a non-lethal dose of LPS (2 mg) i.p. at 8 weeks and compared to allografted controls treated with vehicle. Urine protein was measured every 4 weeks. Rats in the treated group were sacrificed at 12 and 16 weeks, control animals at 12, 16 and 24 weeks (20/group) and examined histologically. In the chronically rejecting control allografts, progressive interstitial and glomerular sclerosis and vascular intimal proliferation had become apparent by 12 weeks. Infiltration of glomeruli, particularly by macrophages (M phi), and the coincident presence of cytokines were prominent, peaking at 16 weeks. LPS treatment accelerated and intensified these changes; proteinuria was more pronounced (16 weeks: 79 mg/24 h vs. 49 mg/24 h, p < 0.05). Numbers of infiltrating M phi peaked at 12 weeks in LPS treated hosts (69 c/FV vs. 27 c/FV in untreated controls, p < 0.01), accompanied by an increased upregulation of MHC class II and cytokine expression, particularly TNF alpha and PDGF around arteries and areas of infiltration. BY 16 weeks, 35 +/- 3% of glomeruli in LPS treated recipients had become sclerotic vs. 15 +/- 6% (p < 0.05) in controls, again associated with increased expression of cytokines (PDGF, TNF alpha, TGF beta), adhesion molecules (ICAM-1) and extracellular matrix proteins. Overall, the extent of chronic rejection of grafts in LPS treated rats at 16 weeks was similar to that developing in non-treated rats at 24 weeks. Activation of graft endothelium and/or host leucocytes increased the pace of graft infiltration and the expression of cytokines and other molecules. These events accelerate the process of chronic rejection.

Analysis of Variance↗