Biomedical subjects

G Stein

Publications and source records attributed to G Stein.

At least 19 recordsLinked to original sources

PubMed2006

DNA fragmentation in chronic glomerulonephritis: an immunohistological analysis.

BACKGROUND: Experimental data suggest that apoptosis plays an important pathophysiological role in glomerulonephritis by restoring tissue structure after proliferation of intrinsic renal cells and infiltration of leukocytes. Relatively little is known of apoptosis in human glomerulonephritis, particularly in predicting renal function during follow-up. METHODS: In order to colocalize different markers for cell damage in renal tissue from patients with different forms of glomerulonephritis (GN), a series of semithin sections from 34 kidney biopsies were studied retrospectively. Normal kidney from a nephrectomy specimen with a small renal adenocarcinoma served as a control. DNA fragmentation, expression of tissue transglutaminase II, BAX and BCL-2 were visualized immunohistochemically. In some renal biopsies, immunohistochemical staining for activated caspase 3 was performed. Proinflammatory markers (C-reactive protein, leukocytes), serum creatinine, creatinine clearance, total proteinuria, albuminuria, alpha(1)-microglobulin and IgG excretion were determined at the time of biopsy. Serum creatinine and total proteinuria were assessed 6 and 12 months after renal biopsy. RESULTS: Nuclei with different degrees of DNA fragmentation were mainly found in epithelial cells of tubules, but also in glomerular cells, regardless of the form of GN studied. Transglutaminase II expression was found only in cells with a strong staining for DNA fragmentation. DNA fragmentation localized to glomerular cells was more pronounced in proliferative than in non-proliferative forms of GN, being most abundant in patients with rapid progressive GN. Staining for activated caspase 3 in selected biopsies confirmed the presence of apoptosis. BAX and BCL-2 staining was detected within the same cells, but exhibited a different intracellular distribution. In proliferative GN, the extent of DNA damage in tubular epithelial cells significantly corresponds with the concentration of serum creatinine (p < 0.04) and with urinary excretion of alpha(1)-microglobulin (p < 0.01) at the time of biopsy. A significant correlation (p < 0.01) was seen between glomerular DNA fragmentation and follow-up total proteinuria 12 months after biopsy for proliferative forms of GN. The damaged glomerular area (e.g. mesangial sclerosis) significantly correlated with DNA fragmentation in proliferative, but not in nonproliferative GN at the time of biopsy. Furthermore, glomerular damaged showed a significant correlation with tubular DNA damage in proliferative GN. CONCLUSION: In glomerular cells, apoptosis may be important for the clearance of proliferating cells whereas in tubules, cell damage showed dependence on the degree of tubular injury mediated by inflammation and/or proteinuria. Although the degree of apoptosis in tubular cells correlates with serum creatinine in proliferative GN at the time of biopsy, it is of limited use to predict future renal function.

Adult↗

PubMed2006

Asymmetrical (ADMA) and symmetrical dimethylarginine (SDMA) as potential risk factors for cardiovascular and renal outcome in chronic kidney disease - possible candidates for paradoxical epidemiology?

BACKGROUND: Asymmetrical dimethylarginine (ADMA) is an inhibitor of nitric-oxide synthase. It has been linked to atherosclerotic risk in the general population as well as in end-stage renal disease patients (ESRD), whereas symmetrical dimethylarginine (SDMA) is thought to be biological inactive. Prospective data concerning the role of both dimethylarginines are rare in patients with chronic kidney disease. METHODS: 200 Patients with chronic kidney disease (mean age 57.6 +/- 13.0 years, 69 female, 131 male); 82 with chronic renal failure (CRF), 81 on maintenance haemodialysis (HD) and 37 renal transplant recipients (RTR) were prospectively followed for 24 months. ADMA and SDMA were measured by HPLC. The relation of plasma levels of ADMA and SDMA together with conventional risk factors for the cardiovascular and renal outcome was investigated with Cox proportional hazards model. RESULTS: Mean serum levels of SDMA were significantly increased in all groups compared to the control group (P <or= 0.0005), ADMA was increased only in HD and RTR (P <or= 0.004). Forty-seven cardiovascular events (CVE) occurred during follow-up, 35 patients died, and 39 patients reached ESRD. Multivariate analysis showed diabetes (RR 3.072, P = 0.01), ESRD (RR 11.915, P < 0.0005), elevated CRP levels (RR 3.916, P < 0.0005) and surprisingly a lower ADMA level (RR 0.271, P = 0.008) as independent risk factors for CVE. Serum creatinine (RR 11.378, P = 0.001), haemoglobin (RR 0.710, P = 0.038 for an increment of 1 mmol/l), and SDMA levels (RR 1.633, P = 0.006, per 1 micromol/l increment) were predictors for the progression to ESRD. CONCLUSIONS: Data from a heterogeneous group of patients with chronic kidney disease provide evidence that conventional risk factors seem to play a more important role than elevated serum levels of ADMA or SDMA for cardiovascular events. Increasing serum SDMA concentration seems to play an additive role for the renal outcome besides serum creatinine and haemoglobin levels. Whether ADMA might possibly be a candidate for the phenomenon of "paradoxical epidemiology" in chronic kidney disease needs further investigation.

Adult↗

PubMed2006

Overweight, obesity and elevated blood pressure in children and adolescents.

OBJECTIVE: Since many years in adults associations between dyslipidaemia, increased insulin resistance, arterial hypertension and the risk for cardiovascular diseases have been recognized. It was the aim of the present trial to investigate these associations and interactions between height, weight, body-mass index and blood pressure values in overweight/obese and normal weight children and adolescents. PATIENTS AND METHODS: 172 children and adolescents (n = 86 with overweight and obesity, n = 86 controls) were studied. In all the subjects anthropometrical data and blood pressure values were assessed. RESULTS: Overweight and obese children had significantly higher blood pressure values (systolic 117.9 +/- 9.7, diastolic 75.6 +/- 8.8 mmHg) than control subjects (systolic 111.4 +/- 11.0, diastolic 69.5 +/- 8.8 mmHg, p<0.001/0.001). Additionally in overweight and obese subjects the number of patients with blood pressure values below the 50th percentile was lower, but the numbers of children and adolescents with values >or=50th age-, height- and gender-specific percentiles were significantly higher. In multivariate analysis of overweight/obese children and adolescents only patients' BMI (R-square = 0.26, beta = 0.52, p<0.001), but not sex, age, height or weight revealed any association with systolic blood pressure values. Diastolic blood pressure revealed an association with childrens' and adolescents' weight (R-square = 0.22, beta = 0.48, p<0.001), but there were no associations with body-mass index, sex, age or height. In normal weight control subjects age (beta = 0.32, p = 0.01) and height (beta = 0.28, p = 0.03) showed associations with the systolic blood pressure values (R-square = 0.15), but only childrens' and adolescents' height (beta = 0.39, p<0.001) was associated with diastolic blood pressure (R-square = 0.28). CONCLUSIONS: Overweight and obesity in childhood are highly associated with multiple comorbidities, elevated blood pressure values, dyslipidaemia, reduced insulin sensitivity and alterations of large and minor vessels. Overweight and obesity in children and adolescents should not longer be regarded as variations of normality, but as diseases with an extremely high risk for the development of atherosclerosis and cardiovascular complications in adulthood. Knowledge of these complex associations implicate even in young age the need for intervention.

Adolescent↗

PubMed2006

Osteoprotegerin reduces the loss of periarticular bone mass in primary and secondary spongiosa but does not influence inflammation in rat antigen-induced arthritis.

OBJECTIVE: To assess the effect of osteoprotegerin (OPG) on joint swelling, synovial inflammation and cartilage destruction, periarticular and axial bone volume, and bone turnover in rat antigen-induced arthritis (AIA). DESIGN: Rats were treated with OPG (3 mg/kg/day) at regular intervals from day 1 to day 20 of AIA. Disease activity was evaluated by measurement of joint swelling as well as, joint inflammation and destruction by histology. Bone volume and cellular turnover parameters of secondary spongiosa of the right tibia head and the third lumbar vertebra were evaluated by histomorphometry. Periarticular bone volume of the primary spongiosa at the right tibia head was measured by linear scanning. The findings were compared with those of PBS-treated AIA and healthy animals. RESULT: OPG treatment did not reduce joint swelling or histological signs of inflammation. Cartilage destruction was reduced. However, this effect did not reach statistical significance . In the secondary spongiosa OPG treatment reduced the loss of periarticular bone volume. However, the latter did not reach the level of healthy controls. OPG treatment significantly reduced parameters of bone formation and bone resorption. In the primary spongiosa, OPG-treatment led to a higher amount of mineralized tissue and a greater number of trabeculae compared to PBS-treated animals with AIA or healthy controls. In the axial skeleton, OPG treatment reduced bone formation and bone resorption parameters compared to healthy animals. This treatment had no influence on bone volume. CONCLUSIONS: In periarticular bone of AIA rats, OPG treatment reduced the loss of bone volume and decreased the bone turnover, thus preventing periarticular bone destruction. OPG treatment had no influence on inflammatory process or on cartilage destruction.

Animals↗

PubMed2006

Structured diabetes therapy and education improves the outcome of patients with insulin treated diabetes mellitus. The 10 year follow-up of a prospective, population-based survey on the quality of diabetes care (the JEVIN Trial).

AIMS/HYPOTHESIS: JEVIN (Jena's St. Vincent Trial) is a prospective, 10 year follow-up, population-based survey of all insulin treated patients with type 1 and type 2 diabetes mellitus aged 16 to 60 years and living in the city of Jena (100,000 inhabitants), Thuringia, Germany. It aims to show the effects of implementation of the St. Vincent Declaration and to evaluate the effect of recent changes in the health care system and new treatment strategies. PATIENTS AND METHODS: 190 patients (83% of the target population), 244 patients (90%) and 261 patients (90%) were studied in 1989/90, 1994/95 and 1999/2000, respectively. RESULTS: Up to 1994/95, the HbA1c of patients with type 1 diabetes mellitus increased (1994/95: 8.50+/-1.80% versus 1989/90: 7.83+/-1.60%, p=0.002). For patients with type 2 diabetes mellitus, it remained constant (9.01+/-2.06% versus 9.17+/-1.60%, n. s.). During the period from 1994/95 to 1999/2000, there was a substantial improvement in the relative HbA1c of both, patients with type 1 (7.62+/-1.55%, p<0.0001), and with type 2 diabetes (7.57+/-1.29%, p<0.0001). Up to 1999/2000, 87.7% of the patients with type 1 (1989/90: 0%, 1994/95: 73.2%) and 96.6% of the patients with type 2 diabetes (1989/90: 0%, 1994/95: 89.7%) participated in TTP's. The incidence of acute and the prevalence of long-term complications remained constant. CONCLUSIONS: Results of the population-based, prospective trial to optimise patients' quality of diabetic control suggest: For patients with insulin treated type 2 diabetes mellitus, excellent treatment can be available by primary care physicians interested, educated and highly engaged in diabetes therapy. Moreover, structured diabetes therapy consisting of treatment and teaching programmes, regular self-monitoring, patients' insulin dose adjustment and patients' empowerment, should be offered to all patients with diabetes mellitus.

Adolescent↗

PubMed2006

Postprandial mononuclear NF-kappaB activation is independent of the AGE-content of a single meal.

OBJECTIVE: Dietary uptake of Advanced Glycation Endproducts (AGE) is supposed to potentially contribute to inflammatory reactions linked to vascular dysfunction and late diabetic complications. One mechanism by which dietary AGE might exert these effects is by activation of the proinflammatory transcription factor NF-kappa-B. The aim of this study was to analyze the postprandial effects of a casein meal with low or high AGE content on postprandial NF-kappaB activation in peripheral blood mononuclear cells (pBMC) of healthy volunteers. RESEARCH DESIGN AND METHODS: Casein was heated for 40 h at 50 degrees C in the presence of sorbitol or glucose, resulting in either minimal (Sorbitol [S]-casein) or large (glucose [G]-casein) amounts of AGE-modified casein. Nine healthy volunteers ate 250 g of both types of casein, whereas both meals were separated at least by 2 weeks. Plasma and pBMC were taken before and 2 h after each meal. Thereafter, the defined AGE carboxymethyllysine (CML) was determined by ELISA and Western blot. NF-kappaB activation in pBMC was assayed using Electrophoretic Mobility Shift Assays (EMSA) and Western blot analysis. RESULTS: S-casein contained only minor amounts of CML and no pentosidine, while G-casein contained large amounts of both. 2 h after ingestion, the S-casein or the G-casein-meal, both, resulted in a non-significant increase in plasma CML and in the intracellular CML-content of pBMC. This was paralleled by a highly significant increase in postprandial mononuclear NF-kappaB-binding activity. Remarkably, neither the extent of NF-kappaB induction (178% for S-casein, 188% for G-casein), nor composition of the NF-kappaB heterodimer (mainly consisting of NF-kappaB p50/p65) were significantly different after intake of S-casein or G-casein. Consistently, Western blots confirmed an increased NF-kappaBp65 nuclear translocation and a decrease of NF-kappaBp65 in the cytoplasm, while no difference in postprandial NF-kappaB nuclear translocation was observed following intake of S-casein or G-casein. CONCLUSION: Postprandial mononuclear NF-kappaB activation after a single meal is independent of the AGE-content of the ingested protein.

Active Transport, Cell Nucleus↗

PubMed2006

Advanced glycation end product modification of bone proteins and bone remodelling: hypothesis and preliminary immunohistochemical findings.

BACKGROUND: The process of bone remodelling is disturbed in the development of osteoporosis. OBJECTIVE: To investigate if proteins in osteoporotic bone are modified by advanced glycation end products (AGEs), and whether these alterations are related to measures of bone remodelling based on histomorphometric findings. METHODS: Bone specimens taken from the iliac crest by bone biopsy of eight osteoporotic patients were investigated by histomorphometry and by immunohistochemical staining with the AGEs imidazolone and N(epsilon)-carboxymethyllysine. RESULTS: Both AGEs were found in all bone specimens. The intensity of staining correlated with patient age. The percentage of bone surface covered with osteoblasts showed a significantly negative correlation with the staining intensity of both AGEs. CONCLUSIONS: It is known that AGEs can regulate proliferation and differentiation of osteoblastic cells and that AGE-specific binding sites are present in cultured osteoblast-like cells. Moreover, AGE induced biological effects in these cells might be mediated by RAGE (receptor of AGE) or by other AGE receptors in different stages of osteoblast development. The inverse relation between AGE staining intensity and the percentage of bone surface covered with osteoblasts in the trabecular bone may provide evidence that AGE modification of bone proteins disturbs bone remodelling.

Adult↗

PubMed2006

Diabetes, insulin, and risk of cancer.

Up to now, the studies involving diabetes mellitus and malignancies show controversial results: Many of them have found incidences of malignancies that were comparable or even lower than those in nondiabetic subjects; others conclude that diabetes mellitus is linked to a higher incidence of malignancies and/or a predictor of mortality from cancer. Insulin and its precursors, pro- and pre-proinsulin, have been shown to have some homology to the insulin-like growth factors, but, moreover they have some affinity to bind at receptors of the tumor growth factor and some hybrids too. Hence, an association between diabetes mellitus, insulin, hyperinsulinaemia, and carcinogenesis appears plausible. On the other hand, diabetes mellitus can influence different hormone levels. In some tumor entities, such as prostate carcinoma, this effect can somewhat counterbalance the direct mitogene effect of insulin and its precursors. All in all, as a result of the complexity of these mechanisms and the differences between the tumor entities, the question whether diabetes mellitus is associated with an increased or a reduced risk for the development and in respect of the prognosis of cancer cannot be answered. The only way to give some answer is to focus on specific tumor entities: It seems that diabetes mellitus and/or hyperglycaemia are independent risk factors and/or predictors at least in respect of cancer of the colon, pancreas, female breast, endometrium, and, in men, of the liver and bladder. However, most of these data were assessed in patients with type 2 diabetes mellitus. This makes it highly questionable whether the data can easily be transferred to patients with type 1 diabetes. Moreover, additional potential limitations are that most of the studies do not focus on the treatment modality or the race of participants. In conclusion, up to the present, we have an increased risk for some and a reduced risk for other tumor entities, but still, we cannot give the general answer.

Age Factors↗

PubMed2006

The use of PEG-Hirudin in chronic hemodialysis monitored by the Ecarin Clotting Time: influence on clotting of the extracorporeal system and hemostatic parameters.

AIM: The aim of our study was to investigate the use of polyethylene glycol (PEG)-Hirudin (PEG-H) as an anticoagulant in hemodialysis including drug monitoring with the Ecarin Clotting Time (ECT) in whole blood and to compare this regimen with standard anticoagulant unfractionated heparin (UFH) for influence on hemostatic parameters and clot frequency of the extracorporeal system. PATIENTS AND METHODS: The application of PEG-H as an anticoagulant in patients on chronic HD was studied in 20 patients (12 males, 8 females) from a single center in an exploratory, open-label, controlled, single-blind, dose-finding study. The patients were divided in 2 groups with 10 patients each (Group I and II); both received 3 dialyses with UFH, thereafter Group I received 5 dialyses with PEG-H and Group II 10 dialyses with PEG-H. Starting dose of PEG-H in the first dialysis was a bolus of 0.08 mg/kg bwt, the mean dose of the following HD was 0.041 mg/kg bwt (range 0.026 0.065 mg/kg bwt). PEG-H was applied as an intravenous bolus-dose followed by a 0.9% saline as a placebo-infusion. HD was performed regularly 3 times a week. All dialysis treatments were performed exclusively with a hollow fiber dialyzer type. Fibrinogen, antithrombin III, prothrombin fragments, thrombin-antithrombin and soluble fibrin were measured with commercial tests. ECT was determined in a mechanical coagulometer. A semiquantitative score was given for the presence of clots in the extracorporeal system after each dialysis. RESULTS: PEG-H was effectively used as an anticoagulant in 150 chronic dialysis treatments using ECT as a simple monitoring method. The optimal whole blood concentration for PEG-H is 600-1000 ng/ml. Clotting in the whole extracorporeal system was decreased by 45% (p = 0.059) with PEG-H anticoagulated HD in comparison to UFH. Fibrinogen, prothrombin fragments (F1+2-fragments) and thrombin-antithrombin-complex showed no significant change in comparison with UFH, antithrombin III (AT III) increased to normal concentrations. Highly sensitive coagulation markers such as a soluble fibrin showed a significant decrease (p < 0.001) before and after HD with PEG-H compared with UFH. CONCLUSION: PEG-H can be used effectively as an alternative anticoagulant in patients on chronic HD using ECT as a simple drug monitoring method. The lower frequency of clots in the extracorporeal system, the stronger and more efficient inhibition of coagulation during HD as indicated by soluble fibrin, may have a positive influence on the disturbed blood coagulation of these patients.

Adult↗

PubMed2005

Risk of malignancies in patients with insulin-treated diabetes mellitus: results of a population-based trial with 10-year follow-up (JEVIN).

BACKGROUND: Studies involving diabetes mellitus and malignancies show contradictory results: Many of them have found incidences of malignancies that are comparable or lower, other studies have found higher rates than those of non-diabetic subjects. Hence, the goal of the present trial was to study the possible association between diabetes mellitus and the incidence of malignancies and its outcome in a selection-free population over a longer period of time. - PATIENTS AND METHODS: All the patients (n=291) who participated in the JEVIN (Jena's St. Vincent)- trial (a prospective, 10 year follow-up, population-based intervention survey of all insulin-treated patients with type 1 and type 2 diabetes mellitus aged 16 to 60 years and living in the city of Jena [about 100,000 inhabitants], Thuringia, Germany) were assessed. The baseline examination took place in 1989/90, follow-up examinations were performed in 1994/95 and 1999/2000. - RESULTS: Up to 1999/2000, 2 patients with type 1 and 5 patients with insulin-treated type 2 diabetes mellitus developed a malignancy (incidence 0.0241). The most frequent malignancies were cancer of the colon and rectum (3 of 291 patients, incidence 0.0103). Comparing these data with the incidence of carcinoma of the colon and rectum reported by the Robert-Koch-Institute of Germany (incidence 0.0012) diabetic patients showed a 9.9-fold increased risk (p=0.042). There were no significant differences regarding incidence of total malignancies or carcinoma of the breast, the lung, renal cells or gonads. Correlation and multivariate analyses revealed no associations between the development of malignancies and patients' outcome and diabetes duration, the duration of insulin therapy, insulin dosage, the quality of diabetes control or the presence of diabetes-related long-term complications. - CONCLUSIONS: Conclusive to other data derived from selected cohorts, population-based the JEVIN-trial demonstrate an increased incidence of malignancies of the colon and rectum in insulin-treated patients with diabetes mellitus. However, for further confirmation of these interesting results more studies in larger populations over longer periods of time are necessary to explain the heterogeneous findings in patients with diabetes mellitus of an increased incidence for some cancer entities, but not for others. Knowledge of these mechanisms should have important implications for the direction of strategies to prevent the development of malignancies, or to enhance ability to make an earlier diagnosis and more effective therapies.

Adenocarcinoma↗

PubMed2005

The response of skin perfusion and of rheological and immunological variables to intravenous prostanoid administration in Raynaud's phenomenon secondary to collagenosis.

BACKGROUND: Prostanoids are used in the treatment of Raynaud's phenomenon and acral perfusion disorders secondary to collagenosis. In subjective terms, intravenous administration of these agents produces success in more than 50% of patients. The therapeutic outcome of clinical administration of alprostadil or iloprost may vary from individual to individual. PATIENTS AND METHODS: The following variables were analysed in a cross-over study in 27 patients with collagenosis and Raynaud's phenomenon: plasma viscosity and erythrocyte aggregation (rheological variables), partial pressure of oxygen and laser Doppler flowmetry in the finger region, and lymphocyte phenotyping and interleukin (IL) determinations (immunological variables). RESULTS: Laser Doppler flowmetry revealed significant differences between patients with secondary Raynaud's phenomenon and a control group of 25 healthy subjects. Laser Doppler readings did not change significantly as a result of the treatments. Therapy with iloprost produced a reduction in IL-1beta, L-selectin (CD 62 L) and IL-6. CONCLUSION: The change in immunological variables due to iloprost may explain the long-term effects of prostaglandins in the treatment of Raynaud's phenomenon. From our results it is not possible to infer any preference for iloprost or alprostadil.

Adult↗

PubMed2005

Transdifferentiation of endothelial and renal tubular epithelial cells into myofibroblast-like cells under in vitro conditions: a morphological analysis.

Renal fibrosis is a hallmark of progressive kidney disease and is characterized by an accumulation of extracellular-matrix-synthesizing cells in the glomerulus and tubulointerstitium. This population of myofibroblast-like cells (MFLC) is heterogeneous. It has been experimentally shown, for example, that tubular epithelial cells could change their phenotype into MFLC under certain circumstances, a process called epithelial-mesenchymal transdifferentiation. However, MFLC may also originate from other sources. Therefore, we examined whether endothelial cells (EDC) are able to transdifferentiate into MFLC in vitro. We compared potential differences between syngeneic tubular epithelial cells (EPC) and EDC during transdifferentiation into MFLC using bovine and porcine EDC isolated from pulmonary arteries, and glomerular capillaries. Renal tubular EPC were prepared from bovine renal cortical tissue by collagenase digestion and isolation from homogeneous cell monolayers. Bovine renal tubular EPC stained positive for cytokeratin. Furthermore, tubular EPC selectively incorporated labeled bovine serum albumin, a typical property of differentiated renal tubular cells. EDC were characterized by the absence of epithelial markers (e.g. cytokeratin), but stained positive for vWF. The transdifferentiation of EDC into MFLC occurs sequentially in two steps: First, by a rapid reversible transformation in postconfluent or clonal cultures without the need of cytokine stimulation and second, by a prolonged secondary step in the presence of the transformation-accelerating cytokines and the absence of adherently growing EDC. Thus, EDC that are able to sprout can also irreversibly transdifferentiate into MFLC. On the other hand, prolonged incubation of EPC in the presence of cytokines such as transforming growth factor-beta1 and tumor necrosis factor-alpha leads only to a very small number of MFLC without the ability to further proliferate. Our in vitro data suggest that EDC can more easily transdifferentiate into MFLC than syngeneic renal tubular EPC.

Animals↗

PubMed2005

Dynamics of bone marrow changes in patients with chronic idiopathic myelofibrosis following allogeneic stem cell transplantation.

Scant knowledge exists about the dynamics of fibro-osteosclerotic bone marrow (BM) lesions and regeneration of hematopoiesis following allogeneic peripheral stem cell transplantation (SCT) in chronic idiopathic myelofibrosis. Therefore, an immunohistochemical and morphometric study was performed on BM biopsies in 20 patients before and at standardized intervals (days 30 through 384) following SCT. In responding patients, a total regression of the pretransplant increased fibrosis was completed in the posttransplant period after about six months, while the extent of osteosclerosis did not change significantly during observation time. The quantity of CD61+ megakaryocytes including precursors was strikingly variable after SCT and, by using planimetric methods, atypical microforms exhibiting a dysplastic aspect could be demonstrated. These anomalies may be responsible for posttransplant thrombocytopenia. CD34+ progenitor cells were increased before transplantation, however, their number declined rapidly to normal values in responding patients. Nucleated erythroid precursors revealed a decreased amount before and after SCT accounting for anemia. Large clusters of this cell lineage indicated an initial hematopoietic reconstitution comparable with the expansion of the neutrophil granulopoiesis. Proliferative activity and apoptosis showed an increase until one year after SCT that implied a still regenerating hematopoiesis in keeping with an enhanced cell turnover.

Adolescent↗

PubMed2004

Improvement of the quality of diabetes control and decrease in the concentrations of AGE-products in patients with type 1 and insulin-treated type 2 diabetes mellitus: results from a 10 year-prospective, population-based survey on the quality of diabetes care in Germany (JEVIN).

BACKGROUND: Advanced glycation end (AGE)-products are a complex group of compounds that have been implicated in diabetes related long-term complications. Up to the present only few data exist about serum levels of the AGE-proteins N-epsilon-Carboxymethyllysine (CML) and pentosidine in patients with diabetes mellitus. PATIENTS AND METHODS: In the present 10-year, population-based trial of a selection-free cohort of patients with insulin-treated diabetes mellitus, serum CML and pentosidine levels were examined in correlation to the patients' quality of diabetes control and the prevalence of diabetes related long-term complications. RESULTS: Following the reunification of Germany in 1989 the health care system was decentralised. Up to 1994/95 the relative HbA1c (HbA1c/mean normal) of patients with type 1 diabetes increased (1.65 +/- 0.35 versus 1.52 +/- 0.31, p = 0.002). For patients with type 2 diabetes it remained constant (1.75 +/- 0.4 versus 1.78 +/- 0.31, p = 0.669). During the following period (from 1994/95 to 1999/2000) specialised diabetes care, structured treatment and teaching programmes (TTP), intensified insulin therapy and blood glucose self-monitoring for all patients were broadly implemented. This was accompanied by a substantial improvement in the relative HbA1c of both, patients with type 1 (1.48 +/- 0.3, p<0.0001), and insulin-treated type 2 diabetes mellitus (1.47 +/- 0.25, p<0.0001). During the same period the mean concentration of the AGE-product CML in the sera of patients with type 1 and insulin-treated type 2 diabetes decreased (type 1: 1994/95: 1158.1 +/- 410.0 ng/ml versus 1999/2000: 938.5 +/- 422.4 ng/ml, p<0.0001, type 2: 1994/94: 1244.7 +/- 1231.3 ng/ml versus 1999/2000: 970.9 +/- 458.6 ng/ml, p = 0.007). For pentosidine the same tendency was found for patients with type 1 diabetes (1994/95: 253.6 +/- 280.7 pmol/ml versus 1999/2000: 148.2 +/- 91.4 pmol/ml, p<0.0001). For patients with type 1 diabetes there was a positive correlation between the relative HbA1c-value calculated over the total follow-up period of 10 years and the CML-concentration in 1999/2000 (r = 0.405, p = 0.017). In 1999/2000 a reduced creatinine clearance (</=80 ml/min) was found in 7.8% of patients with type 1 and 14.9% of patients with insulin-treated type 2 diabetes. In comparison to patients with a normal creatinine clearance, patients with a reduced creatinine clearance had not only higher creatinine-concentrations in the sera and higher values of albuminuria but also significantly higher pentosidine levels. CONCLUSIONS: Comparing the data of 1999/2000 with those from 1994/95, there was not only a substantial improvement in patients' quality of diabetes control but also a decrease in the concentration of AGE-products. In patients with diabetes mellitus the AGE-products seem to be mainly influenced by the quality of diabetes control. The decline in renal function leads to increased serum pentosidine levels in patients with insulin-treated diabetes mellitus. Thus it seems that in patients with reduced renal function, higher levels may either play a causal role in the development and progression of nephropathy or they are an epi-phenomenon caused by the decrease in urinary excretion.

Adolescent↗

PubMed2004

Utility of 24-h ambulatory blood pressure measurement in a routine clinical setting of patients with chronic renal disease.

The objective of the study was to investigate the utility of 24 h ambulatory blood pressure measurement (ABPM) in patients with chronic renal disease (CRD). A retrospective audit was performed in an academic nephrology department. ABPMs obtained from 95 consecutive outpatients with nondiabetic renal disease were analysed for their power to stratify disease severity and to predict progression of renal insufficiency during 3 years follow-up. The average of 10 consecutive office blood pressure (BP) readings performed at baseline was used as a reference. Correlations and tabulated statistics were calculated. Baseline mean diurnal BP was 138/87 mmHg by ABPM and 146/92 mmHg by average office BP (56.8 vs 25.3% normotensives, P < 0.01). Mean serum creatinine was 154 +/- 109 micromol/l. Patients without a circadian BP pattern (61%) had significantly higher serum creatinine, urinary albumin excretion and subsequent progression rates of renal failure (P < 0.05). Systolic and pulse pressure ABP values correlated significantly with serum creatinine levels at baseline and 3 years thereafter, independent of daytime (r = 0.23-0.60; P < 0.05). Abnormal nocturnal systolic and mean ABP, and pulse pressure but not average day office BP were significantly associated with abnormal serum creatinine and the presence of coronary heart disease at baseline (relative risk 1.6-1.7, P < 0.05). In conclusion, physicians considered ABPM preferentially in patients with borderline-controlled BP. ABPM provided significant additional information relevant to the clinical decision making process compared with average office BP alone thereby justifying its use in specific situations.

Aged↗

PubMed2004

Development of a standardized susceptibility test for campylobacter with quality-control ranges for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem.

A standardized agar dilution susceptibility testing method was developed for Campylobacter that consisted of testing on Mueller-Hinton medium supplemented with 5% defibrinated sheep blood in an atmosphere of 10% CO2, 5% O2, and 85% N2. Campylobacter jejuni ATCC 33560 was identified as a quality-control (QC) strain. Minimal inhibitory concentration (MIC) QC ranges were determined for two incubation time/temperature combinations: 36 degrees C for 48 hr and 42 degrees C for 24 hr. Quality-control ranges were determined for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem. For all antimicrobial agents tested at both temperatures, 95-100% of the QC MIC results fell within recommended QC ranges. Twenty-one Campylobacter clinical isolates, encompassing five species of Campylobacter (C. jejuni, C. coli, C. jejuni, subsp. doylei, C. fetus, and C. lari) were tested in conjunction with the C. jejuni QC strain. While C. jejuni and C. coli could be reliably tested under both test conditions, growth of C. jejuni subsp. doylei, C. fetus, and C. lari isolates was inconsistent when incubated at 42 degrees C. Therefore, it is recommended that these species only be tested at 36 degrees C.

Campylobacter↗

PubMed2004

Differential expression of beta-chemokines MCP-1 and RANTES and their receptors CCR1, CCR2, CCR5 in acute rejection and chronic allograft nephropathy of human renal allografts.

BACKGROUND: The beta-chemokines MCP-1 (CCL2) and RANTES (CCL5) have been shown to play important roles in acute renal transplant rejection (AR) and chronic allograft nephropathy (CAN). The potential relationship of expression of these chemokines, their chemokine receptors CCR1, CCR2, CCR5, and the cell populations of inflammatory infiltrate, histological and clinical diagnoses were investigated in biopsies at the time of AR and compared with biopsies of CAN. METHODS: In 24 renal transplant biopsies with AR (n = 15) and CAN (n = 9), the expression of MCP-1 and RANTES, their receptors CCR1, CCR2, and CCR5 and the infiltration with monocytes/macrophages and T cells were studied. RESULTS: As previously described, chemokine and chemokine receptor expression was found mainly in mononuclear cells infiltrating the interstitium and glomeruli. In the tubulointerstitial area and glomeruli the expression of MCP-1, RANTES, and their receptors correlated with an infiltration by monocytes/macrophages. Biopsies with CAN revealed a lower expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in tubulointerstitial cells, and a significantly lower infiltration with MRP14-positive monocytes/macrophages than biopsies with AR. In AR, MCP-1 and CCR1 showed a lower expression compared to RANTES, CCR2, and CCR5. CONCLUSIONS: The positive correlation between chemokines and chemokine receptors and infiltrating leukocytes during acute rejection, the lower but detectable expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in CAN, and the differences in the quantity of expression between the different chemokines and chemokine receptors point to a complex regulation of chemokine expression in renal allografts. Since chemokines are not only involved in inflammation but also in tissue regeneration, this could have impact on the development of CAN.

Adult↗

PubMed2004

Influence of hemodialysis membrane permeability on serum levels of advanced glycation end products (AGEs) and homocysteine metabolites.

BACKGROUND: [corrected] Advanced glycation end products (AGEs), total homocysteine (tHcy) and the homocysteine metabolites cystathionine (Cysta) and dimethylglycine (DMG) are increased in serum of patients with end-stage renal disease. The aim of this prospective randomized study was to compare the efficacy of polysulfone high-flux vs. polysulfone low-flux hemodialysis (HD) treatment regarding removal of AGEs, tHcy, Cysta and DMG. PATIENTS AND METHODS: Twenty-nine patients on chronic HD treatment were randomly assigned to 2 groups in a 3-period 2-treatment design with low flux (A)--high flux (B)--low flux (A) for group I and B-A-B for group II, 6 weeks each period. The following parameters were measured in pre- and postdialytic serum samples at baseline and the end of each period: total serum fluorescence, Nepsilon-carboxymethyllysine (CML), free and protein-bound pentosidine, tHcy, Cysta and DMG. RESULTS: There was increased removal of free pentosidine during high-flux HD treatment compared to low-flux HD treatment, attaining significance between the second and third treatment periods (group 1: 86.0 +/- 4.7% vs. 79.2 +/- 8.8%, p = 0.007; group II: 84.0 +/- 6.3% vs. 79.8 +/- 9.8%, p = 0.049 for high vs. low flux). The intradialytic reduction rates for total serum fluorescence, tHcy, Cysta, DMG did not differ between high- and low-flux HD treatment. Protein-bound pentosidine and CML did not decrease during the dialysis sessions, neither with high-flux nor with low-flux HD membrane. Despite a strong decrease during single HD session, the predialytic levels of free pentosidine, tHcy, Cysta and DMG remained unchanged during the study period both for high- and low-flux HD treatment. CONCLUSION: The more pronounced effect of high-flux dialysis on the removal rate of free pentosidine, found in this randomized crossover study, could not translate into a significant difference in predialysis levels after a 6-week treatment period. We could not find any differences between polysulfone high- and low-flux membranes for lowering predialytic serum concentrations of the measured AGEs, which are mainly bound on albumin.

Arginine↗