PubMed Health⌕ Search

Biomedical subjects

G A Müller

Publications and source records attributed to G A Müller.

At least 73 records · Page 4Linked to original sources
PubMed1999

Pharmacokinetics of cerivastatin in renal impairment are predicted by low serum albumin concentration rather than by low creatinine clearance.

The influence of renal impairment on the clearance of the new HMG-CoA reductase inhibitor cerivastatin was evaluated. A single oral dose of 300 microg cerivastatin was given to 18 patients with different degrees of renal impairment and 6 healthy controls. Concentrations of total cerivastatin, its fraction unbound, and the total concentrations of the active metabolites M1 and M23 were measured in plasma. Serum concentrations of unbound cerivastatin were calculated for each individual from the concentration of total cerivastatin and cerivastatin's fraction unbound at t = 2.5 hours. In contradiction to what had been expected, renal impairment significantly influenced the pharmacokinetics of cerivastatin. The best correlation to the AUC and Cmax of unbound cerivastatin was found with serum albumin concentration. Also, serum albumin concentration was the only factor significantly correlated to t 1/2 of cerivastatin. Significant but slighter correlation with the AUC and Cmax of unbound cerivastatin was also observed for creatinine clearance and cerivastatin's fraction unbound, while no correlation was observed with total plasma protein. No significant correlation of creatinine clearance, serum albumin concentration, fu, or total plasma protein concentration with the AUC and Cmax of total cerivastatin or the AUC, Cmax or t 1/2 of M1 and M23 was observed. The authors conclude that low serum albumin concentration rather than low creatinine clearance predicts the pharmacokinetics of cerivastatin in renal impairment.

Adult↗
PubMed1999

Complete heart block as a rare complication of treatment with chloroquine.

Antimalarials are well established disease modifying antirheumatic drugs. A rare and underappreciated treatment difficulty is cardiac complication, in particular conduction disturbances. We describe 2 more patients that developed complete heart block after high dose, longterm treatment. Patient 1, a 73-year-old woman with longstanding rheumatoid arthritis, had taken chloroquine (250 mg/day) for 12 years when she developed complete heart block requiring a permanent pacemaker. Patient 2, a 40-year-old woman with discoid lupus erythematosus, was taking chloroquine from 1979 until 1996. Depending on the clinical disease activity, she intermittently increased the dose from 250 to 750 mg/day. In 1994, she developed complete heart block and a permanent pacemaker had to be implanted. Intensive investigations in both cases did not reveal another underlying cause for conduction disturbances; the atrioventricular block was probably due in both cases to chloroquine related cardiac toxicity. This toxicity seems to be restricted to longterm, high dose treatment; however, it should be kept in mind in patients with preexisting conduction disturbances during longterm treatment.

Adult↗
PubMed1999

Immunohistochemical analysis of HLA class II antigens and tumor infiltrating mononuclear cells in renal cell carcinoma: correlation with clinical and histopathological data.

Cryostat sections of 37 renal cell carcinomas (RCC)--25 clear cell type, 10 granular and 2 chromophobe--were studied with indirect immunoperoxidase method applying monoclonal antibodies (MoAb) to HLA-DR, -DP and -DQ antigens for analysis of HLA class II antigens, and anti-CD14, -CD3, -CD4 and -CD8 MoAb for tumor infiltrating mononuclear cells (TIM). Number of positive cells was estimated semiquantitatively and results of immunohistochemical investigation were correlated with clinical (patient age and sex, tumor size and TNM stage) and histopathological (cytology, histology, grade) characteristics of RCC. All RCC expressed HLA-DR, 92% -DQ and 73% -DP antigens with level of expression in hierarchy- DR>-DQ>-DP, but no statistically important correlation could be established with any of the histopathological or clinical parameters analyzed. Monocytes were more abundant than T lymphocytes and CD4+ than CD8+ T cells, whereas tumors with T lymphocyte predominance and approximately equal number of CD4+ and CD8+ T cells had greatest average diameter. Inadequate activation of T lymphocytes by tumor cells (despite capability of antigen presentation) could be the reason for association of parameters which indicates more aggressive tumor behavior with aberrant HLA class II antigen expression on RCC.

Adult↗
PubMed1999

HLA class I antigens expression in renal cell carcinoma: histopathological and clinical correlation.

Immunohistochemical analysis of HLA class I antigens expression in 26 renal cell carcinomas (RCCs)--18 clear cell, 6 granular and 2 chromophobe--was performed with indirect immunoperoxidase method. Results were correlated with extent and immunophenotype of tumor infiltrating mononuclear cells, histopathological (histology, cytology, grade, presence of necrosis) and clinical (tumor diameter, TNM classification) characteristics of RCC. 4 (15%) RCCs showed reduced HLA class I presence and this was associated with greater tumor diameter and more frequent T3, T4 and M1 stage. All tumors with altered HLA class I antigens expression were grade 2 or 3 and strong correlation with presence of necrosis (p=0.006) was noticed, while mononuclear cell infiltrates (especially CD8+ T lymphocytes) were less extensive compared to tumors with normal HLA class I level. Our results suggest more aggressive clinical behavior of RCCs with reduced HLA class I antigens expression, probably due to impaired cellular antitumor immune response.

Aged↗
PubMed1998

Autologous and allogenic hybrid cell vaccine in patients with metastatic renal cell carcinoma.

OBJECTIVE: To evaluate the safety, acute and long-term toxicity and therapeutic activity of an allogenic and an autologous hybrid cell vaccine in patients with progressive metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Eleven patients were vaccinated with a lethally irradiated hybrid cell vaccine of allogenic RCC tumour cells fused with major histocompatibility complex class I-matched and class II-unmatched activated allogenic lymphocytes. These patients were then followed for a mean of 11 months. Another 13 patients were vaccinated with a hybrid cell vaccine of autologous tumour cells fused with allogenic activated lymphocytes and followed for a mean of 6 months. RESULTS: Six of the 11 patients receiving the allogenic vaccination showed an initial response, with two complete and two partial responses to date. Only three patients who received autologous vaccination responded to treatment. CONCLUSIONS: Hybrid cell vaccination is a promising new approach in the treatment of patients with advanced RCC.

Cancer Vaccines↗
PubMed1998

Characteristics of urea transport of cells derived from rabbit thick ascending limb of Henle's loop.

BACKGROUND: The thick ascending limb of Henle's loop (TALH) is thought to be involved in the regulation of the renal urea gradient. METHODS: We have characterized the uptake of urea (oil density centrifugation and 2-compartment-culture) and volume regulation (impedance measurement) in highly differentiated cells derived from rabbit outer medulla. RESULTS: TALH cells exposed to 600 mOsm/liter (300 mM urea) shrunk to 72 +/- 5% of the isoosmotic volume. Due to a regulatory volume increase (RVI), the cell volume was almost completely regained at 92 +/- 6% after five minutes. The uptake of 14C-urea in the presence of urea concentrations up to 600 mM did not show any saturation. In the presence of phloretin the urea uptake decreased to 69 +/- 14%. The transport was sodium and chloride independent. Changing the membrane potential caused an increase of regulatory volume increase and urea uptake. Hyperosmolarity induced by sucrose (300 mM) and NaCl (150 mM) caused a decrease of urea uptake to 70 +/- 14% and 53 +/- 11%, respectively. The permeability coefficient (P) in a two compartment culture was P = 1.7 . 10(-6) +/- 0.39.10(-6) cm/second, suggesting a relatively low permeability. CONCLUSION: Due to the low permeability, it seems impossible to achieve a physiologically significant participation of the TALH in the urea circulation within the nephron. However, the results of this study provides significant hints about the existence of a specific urea transport mechanism that enables the cell to adapt rapidly to different osmolarities.

Acetamides↗
PubMed1998

Endothelial vasoconstrictor prostanoids, vascular reactivity, and acute renal failure.

The interaction of endothelium-derived vasoconstrictor prostaglandins, the angiotensins (Ang), and the sympathetic nervous system in acute renal failure still remains to be determined. In this study, acute renal failure (ARF) was induced in male Wistar Kyoto rats (N = 7) in a 2K/2C model of 30-minute clamping. Contractions to Ang I and II and norepinephrine (NE) were studied in isolated aortic and renal artery rings 24 hours after clamp release. Sham-operated animals served as controls (N = 7). In ARF, contractions to NE were increased in the aorta and even further enhanced in the renal artery (P < 0.05 to 0.001), whereas contractions to Ang I and II were blunted (P < 0.05). Contractions were inhibited by SQ 30741, a thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist. We conclude that ARF is characterized by abnormal vascular reactivity both in the renal as well as the systemic vasculature that is in part mediated by endothelium-derived vasoconstrictor prostaglandins.

Acute Kidney Injury↗
PubMed1998

Preventive strategies in endothelin-induced renal failure.

The endothelial vasoconstrictor endothelin (ET) can induce acute renal failure when fibrinolysis and vasodilatory prostanoids (PGs) are inhibited. This study compares therapeutic agents preventing ET-induced acute renal failure in anesthetized female pigs. We investigated the effect of four ET boli (1.5 microg/kg, i.v.) after pretreatment with indomethacin (2 mg/kg) and epsilon-aminocaproicacid (100 + 50 mg/kg) alone (controls, group 1) or during additional nifedipine (10 microg/kg/h; group 2), hirudin (0.5 mg/kg; group 3), or enalapril (2 x 0.15 mg; group 4) on coagulation, PGs, and renal function. The ET-induced blood pressure increase was lower in groups 2 to 4 (lowest in group 3, P < 0.05). PG synthesis was blocked in all groups. The initial hypercoagulability (controls) resulted in disseminated intravascular coagulation that was prevented by hirudin and was attenuated in groups 2 and 4. At the end of the experiment, creatinine clearance was significantly (P < 0.05) decreased. The recovery of renal function two hours after the last ET bolus was most pronounced in the hirudin group. All therapeutic drugs attenuated ET-induced impairment of renal function. Hirudin seems to be the most potent protective drug. Prevention of further ET release evoked by ET-mediated secretion of thrombin might explain this. These results suggest three important pathways for ET's hemodynamic and renal effects.

Acute Kidney Injury↗
PubMed1998

Activity of free radical scavenging enzymes in red cells and plasma of patients undergoing extracorporeal low-density lipoprotein apheresis.

There is evidence that reactive oxygen species (ROSs) are generated in extracorporeal circuits. Free radical scavenging enzymes (FRSEs) such as glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) protect against the damaging effect of ROSs. The influence of extracorporeal treatment on FRSE activity was investigated in the plasma and red blood cells (RBCs) of 21 patients undergoing regular low-density lipoprotein (LDL) apheresis. The FRSEs GSSG-R, GSH-Px, and SOD were measured. Determinations were made before and after a single treatment. Because all apheresis patients suffered from coronary heart disease (CHD), 201 CHD patients and 90 individuals without CHD, neither group undergoing apheresis, served as controls. In apheresis patients, GSH-Px (33.9+/-8.2 U/g Hb) and GSSG-R (7.6+/-0.9 U/g Hb) activities were increased whereas SOD activity (5.4+/-1.5 U/g Hb) was decreased in RBCs before a single treatment compared to controls. Plasma FRSEs of apheresis patients were not different from those of controls. There was no effect of a single treatment on FRSEs in RBCs. However, a significant decrease in plasma GSH-Px activity (209.9+/-24.9 U/ml) due to the extracorporeal treatment was observed. These data show that long-term extracorporeal therapy with LDL apheresis modulates the activity of antioxidant enzymes in RBCs whereas a single treatment was without major effect on FRSE activity in RBCs and plasma, except for plasma GSH-Px.

Adult↗
PubMed1998

Oxidative stress during dialysis: effect on free radical scavenging enzyme (FRSE) activities and glutathione (GSH) concentration in granulocytes.

BACKGROUND: Living cells are protected by free radical scavenging enzymes against oxygen radical-mediated damage. It has been suggested that granulocytes are activated on the surface of dialyser membranes, resulting in the generation of free radicals. We have recently reported a lack of plasma lipid peroxidation and unchanged glutathione peroxidase (GSH-Px) as well as glutathione reductase (GSSG-R) activities in red blood cells of haemodialysis patients. However, because mature red cells are free of DNA and RNA, free radical scavenging enzymes (FRSE) cannot be regulated on the gene level in response to an acute oxidative stress. In contrast to erythrocytes, granulocytes are nucleated cells and FRSE protein concentrations can therefore be modulated. METHODS: GSH-Px, GSSG-R, superoxide dismutase (SOD) activities and total glutathione (GSH) were determined spectrophotometrically using a Cobas Fara semi-automatic analyser in granulocytes of 31 healthy blood donors and in 28 patients with chronic renal failure (CRF) for more than 6 months before as well as immediately after a single dialysis treatment. Patients were treated either by haemodialysis (n = 17) using low-flux polysulphone membranes or by haemofiltration (n= 1l) usings high-flux polysulphone membranes. RESULTS: Compared to healthy controls, SOD and GSSG-R activities were increased in granulocytes of HD and HF patients, GSH and GSH-Px were decreased before a single treatment. After dialysis SOD and GSH-PX activities were significantly induced by both HD and HF whereas GSSG-R activities and GSH were decreased. CONCLUSIONS: These results show that the enzymatic defence against oxygen radicals can be induced in granulocytes of patients undergoing regular dialysis treatment, whereas the non-enzymatic defence is compromised as shown by decreased GSH concentrations, both suggesting increased oxidative stress.

Adult↗
PubMed1998

Anaphylactoid reactions during hemodialysis in sheep are ACE inhibitor dose-dependent and mediated by bradykinin.

Anaphylactoid reactions (AR) have been attributed to the generation of bradykinin (BK) when AN69 membranes are used together with angiotensin converting enzyme (ACE) inhibitors during hemodialysis. However, conclusive evidence for the involvement of the BK as the mediator of these AR is still lacking. This study examined the degree of contact activation in an animal model caused by three PAN membranes--AN69, PAN DX, and SPAN- and the effects of different doses of the ACE inhibitor enalapril (ENA) and the BK B2-receptor antagonist icatibant on AR during hemodialysis. Six sheep were dialyzed for one hour with or without ENA pre-treatment using the different membranes in random order. Severe AR were observed only during hemodialysis with AN69 dialyzers together with ENA pre-treatment; the severity of AR increased with the ENA dose. Mild hypotension was noted during hemodialysis with AN69 without ACE inhibition and with PAN DX and 20 mg ENA. Compared to pre-dialysis values, maximum generation of BK after blood passage through the dialyzer was found at five minutes: 73-fold (AN69 without ENA), 161-fold (AN69 with 10 mg ENA), 97-fold (AN69 with 20 mg ENA), 108-fold (AN69 with 30 mg ENA), 154-fold (AN69 with 30 mg ENA and 0.1 mg/kg icatibant), 18-fold (PAN DX without ENA), and 42-fold (PAN DX with 20 mg ENA). Elevated BK levels in arterial blood were detected during hemodialysis with AN69 membranes even without ACE inhibition (2.5-fold); pre-treatment with 20 mg ENA further increased arterial BK concentrations (4-fold). Furthermore, a marked decline of prekallikrein and high molecular weight kininogen concentrations was noted for both AN69 and PAN DX membranes. Anaphylactoid reactions during hemodialysis were completely prevented by icatibant even after pre-treatment with ENA and in the presence of high BK concentrations. Concentrations of prekallikrein, high molecular weight kininogen, and BK remained unchanged and no AR were observed during hemodialysis with SPAN and pre-treatment with 20 mg ENA. Our findings confirm that AR during hemodialysis with the negatively charged AN69 membrane are mediated by BK, since they can be prevented by the BK B2-receptor antagonist icatibant.

Acrylic Resins↗
PubMed1998

Isolation and characterization of the lower portion of the thin limb of Henle in primary culture.

To further characterize cells of the lower portion of the thin limb of Henle (TLH1p) under defined conditions in vitro, we developed a technique to enrich this cell population in suspension. TLH1p cells were isolated by enzymatic digestion of rat inner medulla, elimination of collecting ducts by lectin-coated beads, and differential centrifugation. Immunohistochemical staining of primary cultures of TLH1p cells with various markers revealed the preparations to be > 90% pure. The hormonal stimulation pattern of PGE2 and cAMP production by arginine vasopressin, angiotensin II, and dopamine in the isolated cells also argued against significant contamination by other cell types. Staining with an antibody against the aquaporin-1 water channel showed the distribution of cells from the ascending and descending limbs to be approximately equal in the isolated population. This technique allows the enrichment of cells from the lower portion of the thin limb of Henle in suspension to a very high degree of purity with the option to start primary cultures. Because these segments of the tubular system in particular are relatively inaccessible for microdissection, the presented method renders the possibility of addressing new questions regarding these tubular segments under defined conditions in vitro.

Animals↗