Biomedical subjects

Uwe Heemann

Publications and source records attributed to Uwe Heemann.

At least 19 recordsLinked to original sources

PubMed2007

Comparative analysis of predictive biomarkers for therapeutical strategies in colorectal cancer.

BACKGROUND: Prognostic information regarding the risk of postoperative tumor recurrence defined by a profile of serological, morphological and/or molecular markers can have potential value, particularly for patients with colorectal carcinoma (CRC) of the International Union Against Cancer (UICC) stage II/III who may benefit from adjuvant chemotherapy after surgery. METHODS: A retrospective study of 783 patients with CRC (UICC I-III) including a subgroup analysis of 116 subjects was conducted to determine preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and p53 serum levels. In addition, protein and gene expression of p53, CEA, and adenomatous polyposis coli (APC) was assessed in the tumors of those patients. The values of all serological, morphological, and molecular parameters were correlated with clinicopathological characteristics for their predictive value of tumor recurrence over a mean follow-up period of 32 +/- 6.2 months. RESULTS: Serum CEA but not CA 19-9 or p53 was a significant prognostic factor for disease-free survival, along with UICC and T/N stage. When comparing elevated CEA, CA 19-9, and p53 serum levels with expression of the markers in the tumors, their overall expression was found to be 61.3% in the serum versus 93.5% in the tumor in analyzed patients (n = 116). In particular, all patients in UICC stages I-III who demonstrated at least three elevated markers (CEA/CA 19-9/p53) in serum and/or in the tumor presented with tumor recurrence/metastases. CONCLUSION: Overall increased p53, CEA, and CA 19-9 serum levels and their marker expression in the tumor may be used at the time of primary tumor removal for defining patients at risk for tumor recurrence.

Adenocarcinoma↗

PubMed2006

OKT3 therapy in addition to tacrolimus is associated with improved long-term function in patients with steroid refractory renal allograft rejection.

BACKGROUND/AIMS: The aim of this study was to evaluate long-term allograft salvage rates of patients with steroid refractory allograft rejection after kidney transplantation and to identify factors indicating a successful outcome. PATIENTS AND METHODS: Fifty patients with continuing rejection after high-dose steroids were included in the study. Baseline immunosuppression was switched from cyclosporine to tacrolimus in all patients. Twenty patients additionally received OKT3 as antirejection therapy. Patients having received a cadaveric renal transplant in 1995, excluding patients with steroid resistant rejection, were chosen as a control cohort. RESULTS: Patient survival rates were 96% (n = 48) and 90% (n = 45) and allograft survival rates were 66% (n = 33) and 62% (n = 31) after 5 and 7 years following steroid refractory renal allograft rejection. Graft survival within the control cohort was 73% after 5 years and 69% after 7 years. Creatinine clearance increased from 20 +/- 15 ml/min/1.73 m2 at the start of tacrolimus therapy to 37 +/- 29 ml/min/1.73 m2 and to 32 +/- 26 ml/min/1.73 m2 after 5 and 7 years. OKT3 treatment predicted successful rescue therapy (p = 0.005 and p = 0.04 after 5 and 7 years). CONCLUSION: Our data indicate a reasonable graft survival in steroid refractory renal allograft rejection using tacrolimus. OKT3 treatment in addition to tacrolimus therapy may be beneficial for long-term allograft survival.

Adult↗

PubMed2006

Lithium poisoning: pharmacokinetics and clearance during different therapeutic measures.

The clinical features and pharmacokinetics of 22 lithium overdoses are described. Effectiveness of different treatment regimens regarding elimination of lithium is discussed. Origin of overdose was due to deliberate poisoning or precipitated by concomitant diseases, coadministration of drugs, or combination of both. Treatment included supportive care, diuretics (15/22), hemodialysis (HD; 9/22), and mechanical ventilation (3/22). Severity of lithium intoxication was classified in 50% as I degrees, in 41% as II degrees, and in 9% as III degrees according to Hansen and Amdisen. Renal impairment on admission was diagnosed in 82% of the patients. Half-life of lithium in serum was 3.5 +/- 0.8 hours during the first HD, and 29 +/- 14 and 29 +/- 6 hours during therapy with diuretics or supportive treatment, respectively. Lithium clearance during HD was 160 +/- 15 mL/min, and renal clearance during HD or treatment with diuretics was approximately 20 and 15 +/- 9 mL/min, respectively. Renal lithium clearance was not influenced by HD therapy. There was no difference regarding half-life and clearance between the group that had an unspecific treatment or the group treated with diuretics. Hemodialysis is the therapy of choice for emergent extracorporeal lithium elimination. Renal impairment and interaction with other drugs were the main reasons for intoxication; thus, more cautious prescription or more frequent supervision of this patient group is warranted. It seems that treatment with diuretics does not have a beneficial effect in the overdose setting.

Amiloride↗

PubMed2006

Association between heat shock protein 70s and toll-like receptor polymorphisms with long-term renal allograft survival.

Long-term renal allograft survival has not improved significantly in recent years and only a minority of grafts survives for more than 15 years. To evaluate the association between HSPA1A G(190)C, HSPA1B A(1267)G and TLR4 A(299)G polymorphisms and allograft survival we analyzed DNA of patients with long-term renal graft function over 15 years (Tx15), consecutively transplanted recipients (Tx), patients with acute rejection and healthy controls. HSPA1B (1267)AA was less prevalent in Tx versus Tx15 (P = 0.02) and versus controls (P = 0.004). HSPA1B (1267)GG was more frequent in Tx versus Tx15 (P = 0.005) and versus controls (P = 0.002). HSPA1B (1267)G allele occurred more often in Tx versus Tx15 (P = 0.03), and versus controls (P = 0.02). TLR4 (299)AG genotype prevalence was increased in Tx15 versus Tx (P = 0.02), while TLR4 (299)G allele was more frequent in Tx15 versus Tx (P = 0.02). The increased frequency of HSPA1B (1267)AA and TLR4 (299)AG genotypes in Tx15 group indicates that better cytoprotective functions in HSPA1B (1267)AA and reduced proinflammatory response in TLR4 (299)AG carriers might have improved renal allograft survival.

Aged↗

PubMed2006

Prophylaxis of contrast material-induced nephropathy in patients in intensive care: acetylcysteine, theophylline, or both? A randomized study.

PURPOSE: To prospectively compare the protective effect of acetylcysteine, theophylline, and both agents combined in patients who are admitted to the intensive care unit with at least one risk factor for contrast material-induced nephropathy and who receive at least 100 mL of iodinated contrast medium. MATERIALS AND METHODS: Institutional ethics review board approval and informed consent were obtained. A total of 91 patients (mean age, 58.5 years+/-14.8 [standard deviation]; 31 women, 60 men; 150 examinations) were admitted to the intensive care unit with at least one risk factor for contrast-induced nephropathy and received either (a) 200 mg theophylline 30 minutes before contrast medium administration (group T), (b) 600 mg acetylcysteine twice daily on the day of and (if possible) the day before the examination (group A), or (c) both agents combined (group AT). The primary endpoint for this study was the incidence of contrast-induced nephropathy (chi2 test). RESULTS: Groups T, A, and AT were comparable with regard to baseline creatinine levels and the amount of contrast medium administered. The incidence of contrast-induced nephropathy in groups T, A, and AT was 2%, 12%, and 4%, respectively, and was significantly lower in group T than in group A (P=.047). There was no significant difference in the incidence of contrast-induced nephropathy between groups A and AT (P=.148) or between groups T and AT (P=.53). For group A, serum creatinine did not change after 12, 24, or 48 hours compared with baseline. Creatinine levels in group T decreased 12 hours (1.19 mg/dL+/-0.58; P=.008) and 48 hours (1.16 mg/dL+/-0.55; P=.034) after contrast material injection compared with baseline (1.25 mg/dL+/-0.61). In group AT, creatinine significantly decreased 24 hours (1.21 mg/dL+/-0.74; P=.003) and 48 hours (1.17 mg/dL+/-0.69; P<.001) after contrast material injection compared with baseline (1.28 mg/dL+/-0.74). Group A had significantly higher maximal increases in creatinine than groups T and AT (P=.014). CONCLUSION: For prophylaxis of contrast-induced nephropathy in patients who are admitted to the intensive care unit and who receive 100 mL or more of contrast medium, theophylline is superior to acetylcysteine.

Acetylcysteine↗

PubMed2005

Two corticosteroid-free regimens-tacrolimus monotherapy after basiliximab administration and tacrolimus/mycophenolate mofetil-in comparison with a standard triple regimen in renal transplantation: results of the Atlas study.

BACKGROUND: The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients. In this study we compared two corticosteroid-free tacrolimus-based regimens with a standard triple therapy. METHODS: This was a 6-month, phase III, open-label, parallel-group, multicenter study. The total analysis set comprised 451 patients, randomized (1:1:1) to receive tacrolimus (Tac) monotherapy following basiliximab (Bas) administration (n=153), Tac/mycophenolate mofetil (MMF) (n=151), or, Tac/MMF/corticosteroids triple therapy as a control (n=147). RESULTS: The study was completed by 91.2% (triple therapy), 94.7% (Tac/MMF), and 82.4% (Bas/Tac) of patients. Patient baseline characteristics were similar in all groups. The incidences of biopsy-proven acute rejection were 8.2% (triple therapy), 30.5% (Tac/MMF), and 26.1% (Bas/Tac), p<0.001 (multiple test for comparison with triple therapy); Bas/Tac vs. Tac/MMF, p=ns. The incidences of corticosteroid-resistant acute rejection were 2.0%, 4.0%, and 5.2%, p=ns. Graft survival (95.9%, 96.7%, and 94.7%, p=ns) and patient survival (100%, 99.3%, and 99.3%, p=ns) were similar in all groups. Median serum creatinine at month 6 was 123.0 micromol/L (triple therapy), 134.7 micromol/L (Tac/MMF) and 135.8 micromol/L (Bas/Tac). The overall safety profiles were similar; differences (p<0.05) were reported for anaemia (24.5% vs. 12.6% vs. 14.5%), diarrhoea (12.9% vs. 17.9% vs. 5.9%), and leukopenia (7.5% vs. 18.5% vs. 5.9%) for the triple therapy, Tac/MMF, and Bas/Tac group, respectively. The incidences of new-onset diabetes mellitus were 4.6%, 7.1%, and 1.4%, respectively. CONCLUSION: Corticosteroid-free immunosuppression was feasible with the Bas/Tac and the Tac/MMF regimens. Both corticosteroid-free regimens were equally effective in preventing acute rejection, with the Bas/Tac therapy offering some safety benefits.

Adrenal Cortex Hormones↗

PubMed2005

A randomized, double-blind, placebo-controlled trial on restenosis prevention by the receptor tyrosine kinase inhibitor imatinib.

OBJECTIVES: The aim of the present double-blind, placebo-controlled study was to evaluate the efficacy of a systemic imatinib treatment, a potent platelet-derived growth factor (PDGF) receptor kinase inhibitor, for the prevention of recurrent restenosis in patients with in-stent restenosis (ISR). BACKGROUND: Neointima proliferation after stent placement has been associated with the effect of potent mitogenes such as PDGF, and their inhibition has resulted in reduction of neointima formation in experimental models. METHODS: A total of 180 patients with either symptoms or a positive stress test in the presence of angiographically significant ISR were randomly assigned to two treatment arms: imatinib treatment or placebo. Patients received imatinib (600 mg/day) for 10 days starting 2 days before repeat intervention. Angiographic restenosis at follow-up angiography was the primary end point of the study. RESULTS: Repeat angiography was performed in 160 of 180 patients (88.9%). The combined rate of death or MI at one year was 1.0% in patients randomized to either group (p = 0.67). Compared with the placebo group, imatinib treatment did not affect the angiographic restenosis rate (38.8% with imatinib vs. 41.3% with placebo; p = 0.75). Similarly, the need for target lesion revascularization did not differ between both groups (28.1% with imatinib vs. 28.6% with placebo; p = 0.94). CONCLUSIONS: Systemic imatinib therapy does not affect the risk of recurrence in patients with ISR.

Aged↗

PubMed2005

Inhibition of matrix metalloproteinases during chronic allograft nephropathy in rats.

BACKGROUND: Chronic allograft nephropathy (CAN) belongs to the major causes of long-term kidney allograft failure. One of the histologic hallmarks of CAN is interstitial fibrosis, influenced by matrix metalloproteinases (MMPs) that are controlling extracellular matrix (ECM) degradation. Whether MMPs affect the development and progression of CAN is not clear so far. To analyze the role of MMPs in CAN, we investigated the effects of an early and a late application of BAY 12-9566, an inhibitor of MMP-2, -3, and -9 on the development and progression of CAN in a rat kidney-transplantation model. METHODS: Fisher kidneys were orthotopically transplanted into Lewis recipients that were treated with BAY 12-9566 (15 mg/kg per day) or vehicle either for the first 10 days after transplantation (early treatment) or from week 12 to week 20 after transplantation (late treatment). Proteinuria was analyzed every 4 weeks up to week 20 after transplantation when kidney grafts were removed for further analysis. RESULTS: Early MMP-inhibition resulted in a significantly reduced 24-hour protein excretion that was paralleled by a lower grade of CAN after 20 weeks. However, late MMP inhibition starting at week 12 after transplantation resulted in significantly higher proteinuria and a higher grade of CAN as compared with controls. Furthermore, transforming growth factor-beta and platelet-derived growth factor-B chain mRNA levels were significantly increased in these animals. CONCLUSIONS: Inhibition of MMPs early after transplantation reduced the development and progression of CAN but promoted CAN if initiated at later stages. Thus, MMPs are involved in the development and progression of CAN.

Animals↗

PubMed2005

Ultrastructural analysis of the Fisher to Lewis rat model of chronic allograft nephropathy.

Chronic allograft nephropathy (CAN) is the leading cause of graft loss following kidney transplantation. One factor contributing to CAN is chronic alloimmune injury. However, the involvement of alloantigen-dependent and -independent factors in CAN is unclear. The pathomechanism of CAN has been extensively studied by utilizing the Fischer-to-Lewis (F344-to-LEW) rat model. Transplant capillaropathy (circumferential multiplication of the peritubular capillary basement membrane) and transplant glomerulopathy (reduplication of the glomerular basement membrane) have recently been validated clinicopathologically as ultrastructural indicators of chronic alloimmune injury. To investigate the presence of these markers, F344-to-LEW kidneys were examined by electron and light microscopy 32, 40 and 52 weeks after implantation. F344 rats with or without 30-min ischemia of the left kidney following right nephrectomy served as controls. All transplanted rats displayed marked proteinuria. On electron microscopy, transplant capillaropathy, transplant glomerulopathy, and T-cell cytotoxicity (indicator of ongoing cellular rejection) were absent. On light microscopy, the arteries were devoid of intimal fibrosis. Focal-segmental glomerulopathy resembling hyperfiltration injury was encountered, with mild interstitial infiltration, fibrosis, and tubular atrophy. The proteinuria and kidney pathology were more severe in transplanted than in ischemic or uninephrectomized rats. Because chronic-active rejection could not be detected between weeks 32 and 52, we propose that the alloantigen-dependent initial graft injury subsides, but induces the late events: glomerular hyperfiltration, proteinuria, and glomerulosclerosis. Accordingly, the model - in the late phase - is suitable to investigate alloantigen-independent factors of CAN and lacks markers of alloantigen-dependent processes.

Animals↗

PubMed2005

Open prospective multicenter study of conversion to tacrolimus therapy in renal transplant patients experiencing ciclosporin-related side-effects.

The hyperlipidemic and hypertensive effects of ciclosporin constitute a cardiovascular risk. Cosmetic side-effects are known to reduce patients' quality of life. This was a 6-month, open, prospective, multicentre study in 296 adult kidney transplant patients to evaluate the conversion from ciclosporin to a tacrolimus-based regimen. Primary indications for conversion were hyperlipidemia (n =77), hypertension (n = 72), hypertrichosis (n = 32) and gingival hyperplasia (n = 115). At month 6, hyperlipidemia and hypertension were at least moderately improved in 59.1% and 63.5% of patients, and strongly or completely resolved in 29% and 25%. Gingival hyperplasia and hypertrichosis were strongly or completely resolved in 73% and 72% of patients. Mean total cholesterol was reduced from 255 to 218 mg/dl. Mean systolic blood pressure (SBP) was reduced from 152.9 to 137.5 mmHg and mean diastolic blood pressure (DBP) from 90.7 to 85.8 mmHg. Ciclosporin-related side-effects resolved or improved after conversion to tacrolimus.

Adult↗

PubMed2004

Effects of progesterone and selective oestrogen receptor modulators on chronic allograft nephropathy in rats.

BACKGROUND: We recently demonstrated that oestrogens ameliorate the progression of chronic allograft nephropathy (CAN). In our present study, we investigated the role of progesterone and selective oestrogen receptor modulators (SERMs) in this process. METHODS: Female Fisher (F344) kidneys were orthotopically transplanted into intact or ovariectomized female Lewis recipients. Ovariectomized recipients were divided into four groups and were treated with either progesterone alone or in combination with oestradiol, oestradiol alone or vehicle. Intact recipients were divided into three groups and were treated with SERMs such as tamoxifen and one of its new derivatives, droloxifene or vehicle. Animals were harvested 24 weeks after transplantation for histological and immunohistological studies as well as for molecular analysis. RESULTS: Administration of progesterone resulted in increased urinary protein excretion as well as profound glomerulosclerosis and mononuclear cell infiltration. The combined treatment had similar detrimental effects on the development of CAN. In contrast, oestradiol treatment alone improved graft function, reduced glomerulosclerosis and diminished cellular infiltration. SERMs again impaired allograft function and promoted the development of CAN. Renal allograft damage paralleled intragraft mRNA expression of transforming growth factor-beta1 in all groups. CONCLUSIONS: Our results suggest that addition of progesterone diminishes the beneficial effects of oestrogens on the development of CAN in rats. Similarly to progesterone, SERMs worsened long-term renal allograft outcome.

Animals↗

PubMed2004

Suppressed T-cell activation by IFN-gamma-induced expression of PD-L1 on renal tubular epithelial cells.

BACKGROUND: The interaction of the T-cell molecule PD-1 (programmed death-1) with its ligands PD-L1 and PD-L2 represents a known mechanism of T-cell inhibition. PD-1 is homologous to CD28 while the PD-1 ligands share homology with the B7 family of co-stimulatory molecules. METHODS: We have studied surface expression and transcript levels of PD-L1 and PD-L2 on murine renal tubular epithelial cells (TEC) by flow cytometric analysis and reverse transcription-polymerase chain reaction. Western blot analysis was used to confirm protein expression of PD-L1. We also tested the functional role of PD-L1 and PD-1 in antigen presentation. Furthermore, we stained mouse kidney transplants with rejection for the expression of the PD-1 ligands. RESULTS: We found that PD-L1 but not PD-L2 was weakly expressed on unstimulated TEC. Upon stimulation with IFN-gamma, a dose-dependent upregulation of PD-L1 expression was observed. Blockade of the PD-L1/PD-1 pathway with monoclonal antibodies in antigen presentation assays uncovered an inhibitory role of this ligand system in Th1 and Th2 cell activation. Staining for PD-L1 was strong in proximal and distal tubules in mouse kidney transplants with rejection, whereas staining of normal kidneys and syngenic mouse kidney transplants did not reveal PD-L1 expression. PD-L2 was not observed in normal or rejected mouse kidneys. CONCLUSIONS: These data demonstrate that PD-L1 is an inducible renal tubular epithelial antigen that negatively regulates T-cell responses elicited by IFN-gamma-stimulated TEC. We speculate that the PD-1/PD-L1 pathway may play a role in protecting the epithelium from immune-mediated tubulointerstitial injury.

Animals↗

PubMed2004

Randomized, double-blind, placebo-controlled trial of oral sirolimus for restenosis prevention in patients with in-stent restenosis: the Oral Sirolimus to Inhibit Recurrent In-stent Stenosis (OSIRIS) trial.

BACKGROUND: Despite recent advances in interventional cardiology, including the introduction of drug-eluting stents for de novo coronary lesions, the treatment of in-stent restenosis (ISR) remains a challenging clinical issue. Given the efficacy of systemic sirolimus administration to prevent neointimal hyperplasia in animal models and to halt and even reverse the progression of allograft vasculopathy, the aim of the present double-blind, placebo-controlled study was to evaluate the efficacy of a 10-day oral sirolimus treatment with 2 different loading regimens for the prevention of recurrent restenosis in patients with ISR. METHODS AND RESULTS: Three hundred symptomatic patients with ISR were randomly assigned to 1 of 3 treatment arms: placebo or usual-dose or high-dose sirolimus. Patients received a cumulative loading dose of 0, 8, or 24 mg of sirolimus 2 days before and the day of repeat intervention followed by maintenance therapy of 2 mg/d for 7 days. Angiographic restenosis at 6-month angiography was the primary end point of the study. Restenosis was significantly reduced from 42.2% to 38.6% and to 22.1% in the placebo, usual-dose, and high-dose sirolimus groups, respectively (P=0.005). Similarly, the need for target vessel revascularization was reduced from 25.5% to 24.2% and to 15.2% in the placebo, usual-dose, and high-dose groups, respectively (P=0.08). The sirolimus blood concentration on the day of the procedure correlated significantly with the late lumen loss at follow-up (P<0.001). CONCLUSIONS: In patients with ISR, an oral adjunctive sirolimus treatment with an intensified loading regimen before coronary intervention resulted in a significant improvement in the angiographic parameters of restenosis.

Administration, Oral↗

PubMed2004

Association of hypertension with symptoms of benign prostatic hyperplasia.

PURPOSE: We determined whether the intensity of benign prostatic hyperplasia (BPH) symptoms and arterial hypertension are associated. MATERIALS AND METHODS: Baseline data from a large sample of men seeking treatment for BPH symptoms were analyzed retrospectively. BPH symptom intensity (assessed by the International Prostatic Symptom Score [I-PSS] or urinary flow rate [Qmax]) and blood pressure were determined in 9,857 patients with BPH. Normotension was defined as a diastolic blood pressure of 90 mm Hg or less, the absence of the diagnosis hypertension and the lack of antihypertensive medication (in 4,725). Hypertension was concomitantly defined as a diastolic blood pressure of greater than 90 mm Hg (in 1,727), being diagnosed with hypertension (1,950) or the current prescription of anti-hypertensive drugs (3,360 patients). RESULTS: When age and presence of hypertension were used as the independent explanatory variables, each year of age contributed 0.13 points and measured hypertension 1.60 points to I-PSS as the dependent response variable. Similar results were obtained with Qmax as the dependent response variable. In a logistic regression procedure using age, I-PSS and Qmax as the independent explanatory variables, each year of age and each I-PSS point significantly increased the risk of being hypertensive by 5.3% and 5.0%, respectively, while Qmax did not yield a statistically significant contribution to that risk. CONCLUSIONS: We conclude that a significant, age independent association exists between BPH symptoms and hypertension. This finding indicates a common pathophysiological factor for both disease states such as increased sympathetic activity.

Age Factors↗

PubMed2004

Protective effects of FTY720 on chronic allograft nephropathy by reducing late lymphocytic infiltration.

BACKGROUND: Lymphocytic infiltration is obvious throughout early and late stages of chronic allograft nephropathy. Early infiltrating lymphocytes are involved in initial insults to kidney allografts, but the contribution of late infiltration to long-term allograft attrition is still controversial. Early application of FTY720 reduced the number of graft infiltrating lymphocytes, and inhibited acute rejection. The present study investigated the potential of FTY720 to reduce the number of infiltrating lymphocytes even at a late stage, and, thus, slow the pace of chronic allograft nephropathy. METHODS: Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients with an initial 10-day course of cyclosporine A (1.5 mg/kg/day). FTY720, at a dose of 0.5 mg/kg/day, or vehicle was administered to recipients either from weeks 12 to 24 or from 20 to 24 after transplantation. Animals were harvested 24 weeks after transplantation for histologic, immunohistologic, and molecular analysis. RESULTS: FTY720, either initiated at 12 or 20 weeks after transplantation, reduced urinary protein excretion, and significantly ameliorated glomerulosclerosis, interstitial fibrosis, tubular atrophy, and intimal proliferation of graft arteries at 24 weeks after transplantation. Furthermore FTY720 markedly suppressed lymphocyte infiltration and decreased mRNA levels of interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), and platelet-derived growth factor-B (PDGF-B) but enhanced the number of apoptotic cells in grafts. CONCLUSIONS: FTY720 ameliorated chronic allograft nephropathy even at advanced stages. Furthermore, our data suggest that this effect was achieved by a reduction of graft infiltrating lymphocytes.

Animals↗

PubMed2004

Safety of telmisartan in patients with arterial hypertension : an open-label observational study.

OBJECTIVE: To determine whether age, gender, concomitant disease and/or previous or present antihypertensive medication affect the safety or antihypertensive efficacy of telmisartan in the treatment of arterial hypertension. STUDY DESIGN AND METHODS: In this large-scale, open-label postmarketing surveillance study, German physicians systematically documented their observations concerning patients with essential hypertension on case report forms. Patients were treated for 6 months with telmisartan (40-80 mg once daily). Data were analysed using direct group comparisons and multiple linear regression analysis. RESULTS: A total of 19 870 patients (52.3% males, mean age 59.1 years) were evaluated, of whom 47.6, 18.3, 13.2 and 2.1%, respectively, had concomitant hypercholesterolaemia, diabetes mellitus, congestive heart failure and renal insufficiency. In the overall group, adverse events were reported in 1.9% of patients. Global tolerability was rated as very good, good, moderate or poor, respectively, in 74.7, 22.1, 0.7 and 0.5% of patients; tolerability was similar across all subgroups of patients. Telmisartan treatment did not increase serum creatinine or potassium in any subgroup, including >400 patients with impaired renal function (basal creatinine 1.73 mg/dL). Telmisartan had no adverse effects on glucose, triglyceride or cholesterol levels. In the overall group, telmisartan reduced mean +/- SD systolic blood pressure from 171.3 +/- 16.4 mm Hg to 141.3 +/- 12.0 mm Hg and diastolic blood pressure from 99.0 +/- 9.4 mm Hg to 83.4 +/- 6.9 mm Hg. Reductions were very similar between genders, age groups and patients with and without comorbidities, and not dependent on prior or concomitant treatment with other antihypertensive drugs. CONCLUSION: The safety and efficacy of telmisartan found in controlled studies is maintained in a large postmarketing population that included sizeable patient subgroups potentially at higher risk for adverse events.

Adolescent↗

PubMed2003

Apoptosis and treatment of chronic allograft nephropathy with everolimus.

BACKGROUND: Chronic allograft nephropathy (CAN) is responsible for most cases of late kidney allograft loss. However, no effective treatment is available so far. Everolimus (RAD) (40-O [2-hydroxyethyl] rapamycin) is a new immunosuppressive agent with antiproliferative and apoptosis-enhancing effects. We asked whether everolimus can ameliorate CAN even at advanced stages, whether everolimus treatment affects the level of growth factor mRNA, and whether everolimus treatment affects the number of apoptotic cells in the graft. METHODS: We transplanted kidneys from Fisher rats into Lewis rats and treated recipients with everolimus over different time periods. Grafts were analyzed 20 or 28 weeks after transplantation. RESULTS: Everolimus delayed the progression of CAN when started at an early stage. Surprisingly, everolimus even ameliorated CAN when initiated at an advanced stage. Interestingly, apoptosis was more prevalent in treated animals, particularly in those with delayed treatment as compared with controls. CONCLUSIONS: Everolimus ameliorates CAN as a result of antiproliferative or apoptosis-enhancing effects.

Animals↗

PubMed2003

[Nephrology--Part 2. Strategies in the immunosuppression after kidney transplantation].

BACKGROUND: As a result of better prevention and treatment of acute rejection, 1-year kidney graft survival exceeds 90% in most centers. By contrast, the rate of attrition over the long-term did not change during the last decades. As current immunosuppressive agents lack specificity (infection, malignant disease), the search for the ideal immunosuppressive agent or drug combinations continues. The goal is to prevent chronic allograft nephropathy, toxicity, infections, malignancies, and metabolic problems. Long-term immunosuppression should be reliable and stable. PURPOSE: This article is aiming to discuss current strategies such as nephrotoxicity-free therapy, avoidance or withdrawal of steroids, therapy of acute rejection, and immunosuppressive therapy in high-risk patients.

Chronic Disease↗