Biomedical subjects

G Stein

Publications and source records attributed to G Stein.

At least 37 records · Page 2Linked to original sources

PubMed2004

PTH secretion in patients with chronic renal failure assessed by a modified CiCa clamp method: effects of 1-year calcitriol therapy.

BACKGROUND: Secondary hyperparathyroidism (secondary HPT) in patients with chronic renal failure (CRF) is characterized by parathyroid gland hyperplasia and an intrinsic defect in the recognition of parathyroid hormone (PTH) secretion. Conflicting results have been reported regarding the set point for calcium-regulated PTH release and its modification by calcitriol therapy in hemodialysis patients. Additionally, the effect of calcitriol on the calcium/PTH relationship in predialysis CRF patients with early secondary HPT has not been investigated. Our objective in this controlled study was to investigate the calcium/PTH relationship and to determine the calcium set point in patients with early stages of CRF before and after a 1-year treatment with calcitriol and in normal volunteers. METHODS: Nine patients with an early stage of CRF (GFR between 20 and 50 ml/min x 1.73 m2 b.s.) aged 35-77 years and 13 healthy volunteers (HV) aged 26-60, years were included in the study. All participants were investigated by sequential lowering and raising of serum calcium levels comprising the following phases: blood-ionized calcium (Ca2+) was lowered by about 0.2 mmol/l (3 steps), steady-state hypocalcemia of Ca2+ 0.2 mmol/l below the baseline (step 4), stop of the infusion for 5 minutes (step 5), Ca2+ was raised to about 0.2 mmol/l above baseline (steps 6 and 7), and a steady state hypercalcemia of Ca2+ 0.2 mmol/l above baseline (step 8). Ionized calcium and intact PTH (iPTH) were measured at 30 time points during 240 minutes. The calcium set point was determined using the classical 4-parameter model. The CiCa clamp test was performed before and after a 1-year treatment with 0.5 microg of calcitriol thrice weekly. RESULTS: No differences in the set point were observed between HV and CRF patients with early secondary HPT. Four of 9 patients responded to calcitriol treatment with a decrease in basal serum iPTH levels ("responders"). There was no difference between renal function (GFR 18 +/- 6 vs. 17 +/- 8 ml/min x 1.73 m2 b.s.), set point (Ca2+ 1.07 +/- 0.13 vs. 1.07 +/- 0.06 mmol/l) and suppressibility of PTH secretion (PTHmin% 7.3 +/- 1.6 vs. 8.2 +/- 2.9) in responders vs non-responders, nor did these values change after treatment with calcitriol. PTHmin% decreased significantly in the whole group after treatment (10.4 +/- 8.5 vs. 7.8 +/- 2.4). CONCLUSIONS: Although the calcium set point was not different in predialysis CRF patients with early secondary HPT compared to HV, calcitriol treatment improved the calcium-related suppression of PTH secretion (PTHmin%).

Adult↗

PubMed2004

Prediction of cardiovascular risk in hemodialysis patients by data mining.

OBJECTIVES: The objective of this work was to contribute to the development, validation and application of data mining methods for prediction in decision support systems in medicine. The particular focus was on the prediction of cardiovascular risk factors in hemodialysis patients, specifically the interventricular septum (IVS) thickness of the heart of individual patients as an important quantitative indicator to diagnose left ventricular hypertrophy. The work was based on data from 63 long-term hemodialysis patients of the KfH Dialysis Centre in Jena, Germany. METHODS: The approach applied is based on data mining methods and involves four major steps: data based clustering, cluster based rule extraction, rulebase construction and cluster and rule based prediction. The methods employed include crisp and fuzzy algorithms. At each step, logical and medical validation of results was carried out. Different sets of randomly selected patient data were used to train, test and optimize the clusterbases and rulebases for prediction. RESULTS: Using the best clusterbase/rulebase combination designed, the IVS thickness cluster ('small' or 'large') was predicted correctly for 30 of the 35 patients with known IVS values in the training data set; no patient was predicted incorrectly and 5 were parity predicted. For the test data set, 4 of the 6 patients with known IVS values were predicted correctly, no patient incorrectly and 2 parity. These results did not substantially differ from those obtained using the second best clusterbase/rulebase combination which was finally recommended for use based on further performance criteria. The prediction of the IVS thickness clusters of the 22 patients with unknown IVS values also yielded good results that were (and could only be) validated by a medical individual risk assessment of these patients. CONCLUSIONS: The approach applied proved successful for the cluster and rule based prediction of a quantitative variable, such as IVS thickness, for individual patients from other variables relevant to the problem. The results obtained demonstrate the high potential of the approach and the methods developed and validated to support decision-making in hemodialysis and other fields of medicine by individual risk prediction.

Algorithms↗

PubMed2004

Diabetes mellitus and dialysis.

Diabetes mellitus is increasing, and in some countries is the single most important cause, for end-stage renal disease. In general, primarily elderly patients on renal replacement therapy, are not only affected by diabetes-related long-term complications, but also frequently with a wide range of co-morbidities. Apart from cardiac complications, the patients are subject to a wide range of vascular (i.e. peripheral vascular disease, stroke) and infectious complications. In the past this has been reflected by a relatively poor survival rate on dialysis, and minimized chances to obtain renal transplantation. Today, several renal replacement strategies are available, including the main 3: hemodialysis, peritoneal dialysis or kidney transplantation. For patients with diabetes mellitus, hemodialysis is the most commonly used therapy. Each dialysis unit should achieve an optimal dialysis adequacy represented by a single pool Kt/V of at least 1.2. The most important independent predictor of patient survival with hemodialysis treatment is age. Other factors related to complications are left ventricular hypertrophy, arterial hypertension, hypervolaemia and chronic anemia. Moreover, medial arterial calcification, malnutrition, gastrointestinal disorders and dialysis against low potassium dialysate are related to increased morbidity and mortality as well. An integral part of treatment is the availability of good vascular access. The survival rates of fistulas show a nearly twofold higher rate of failure for synthetic grafts compared with arteriovenous fistulas. The role of peritoneal dialysis in renal replacement therapy in patients with diabetic nephropathy is well established and used world-wide. Most patients with residual renal function start with continuous ambulatory peritoneal dialysis (CAPD), but automated peritoneal dialysis can also be used. An unresolved problem associated with CAPD is the glucose absorption and caloric intake. The optimum adjustment of blood glucose values is made more difficult. Death rates of diabetic patients on peritoneal dialysis remain higher than in non-diabetics. The changes in peritoneal membrane thickness and vascular alterations in relationship to the duration of dialysis are caused mainly by glucose and glucose degradation products, such as advanced glycation endproduct (AGEs). Therefore, new peritoneal dialysis solutions are needed to reduce the complications and to delay a long-time function of the peritoneal membrane. Peritonitis remains still the major cause of discontinuation of dialysis but there is no increased risk in diabetic patients. Nevertheless, an integrative care of end-stage renal disease patients with diabetic nephropathy should be offered to the patient, starting on peritoneal dialysis and switch to hemodialysis if problems arise. During the whole time patients should be kept on the renal transplantation waiting list.

Diabetic Nephropathies↗

PubMed2003

Cognitive function and quality of diabetes care in patients with Type-2-diabetes mellitus in general practitioner practice.

INTRODUCTION/AIMS: The goal of the trial was the assessment of the quality of diabetes control and the cognitive function of all patients with type 2 diabetes mellitus treated in a randomly selected general practitioner practice in Thuringia, Germany. Furthermore possible interactions between patients' quality of diabetes control and their cognitive function should be analysed. PATIENTS AND METHODS: The investigation comprised all 141 patients with type 2 diabetes mellitus (age 67.3 +/- 10.5 years, body-mass index 29.3 +/- 4.5 kg/m2, patients without insulin therapy: n = 102, with insulin therapy: n = 39) who were patients at the general practitioner practice in Wandersleben, Thuringia, Germany, between November 1999 and April 2000. RESULTS: The mean HbA1c of all patients examined was 6.33 +/- 1.1% (normal range 3.5-6.8%). 55 patients were treated with diet (HbA1c 5.7 +/- 0.76%) and 47 patients were given oral antidiabetic drugs (HbA1c 6.5 +/- 0.76 %). 27/47 (57.4%) patients were treated with sulfonylurea, 37/47 (78,7%) with metformin, 3/47 (6,4%) with acarbose and 7/47 (14.9%) patients received glinides. 18/47 (38,3%) patients had combinations out of two or more oral antidiabetic drugs. A total of 39 patients with type 2 diabetes mellitus were treated with insulin (HbA1c 7.0 +/- 1.24%). The premorbide cognitive function of the patients was 97.9 +/- 10.0 IQ-points. It was significantly better than the actual cognitive function (91.8+/-13.5 IQ-points, p<0.001). The actual cognitive function showed a correlation with patient's age (r = -0.28, p = 0.001), educational level (r = -0.25, p = 0.006) and profession (r = -0.29, p = 0.001). Performing multivariate analysis the premorbide cognitive function (b = 0.53, p<0.001) and patient's age (b = -0.32, p<0.001) showed associations with the actual cognitive function (R-square =0.36). Associations with the HbA1c (R-square = 0.37) showed the frequency of blood glucose self monitoring (beta = 0.38, p<0.001), the blood glucose value at the time of examination (beta = 0.34, p<0.001) and the diabetes duration (beta = 0.16, p = 0.03). There were no associations between actual cognitive function and other parameters. CONCLUSIONS: The data from this trial presents evidence which shows that treatment by general practitioners can enable patients both with and without insulin therapy to achieve a high quality of diabetes control. Hence, the results derived from ambulatory evaluations of treatment programmes can not be automatically tansferred to patients treated at hospitals. Regarding inpatient treatment, adapted structured treatment and teaching programmes are mandatory.

Aged↗

PubMed2003

Effect of smoking on risk factors for cardiovascular disease in patients with diabetes mellitus and renal insufficiency.

BACKGROUND: Many studies have been published demonstrating a strong correlation between smoking, renal lesions and cardiovascular morbidity and mortality. Possible contributing factors are elevated blood pressure values, changes in vascular reactivity, concentrations of lipids, fibrinogen and carboxyhemoglobin, in patients with diabetes mellitus, the quality of diabetes control and insulin resistance. Other possible risk factors may include advanced glycation end (AGE)-products, total plasma homocysteine and metabolites as well as symmetrical (SDMA) and asymmetrical (ADMA) dimethylarginine. It was the goal of the present trial to investigate the serum concentrations of these >new<, possible risk factors in a selection free population of patients with type 1 and insulin-treated type 2 diabetes mellitus, in patients with chronic renal insufficiency and in renal transplant recipients. The second aim was to analyse the effect of cigarette smoking on the levels of these laboratory parameters. PATIENTS AND METHODS: A total of 544 subjects (n = 98 patients with chronic renal insufficiency without hemodialysis, n = 84 patients with hemodialysis, n = 50 renal transplant recipients, n = 114 patients with type 1 and n = 147 patients with insulin treated type 2 diabetes mellitus, n = 51 healthy controls) participated in the trial. RESULTS: Patients with renal insufficiency had significantly higher concentrations of the AGE-products N-epsilon-Carboxymethyllysine (CML) and pentosidine compared with both groups of patients with insulin-treated diabetes mellitus and the healthy controls. In patients with type 1 diabetes there was a positive correlation between HbA1c and the concentration of CML (r = 0.405, p = 0.017) and between the pentosidine-concentration and the serum creatinine-level (r = 0.482, p = 0.001). In type 2 diabetes there was a correlation between CML and diastolic blood pressure (r = 0.239, p = 0.039). In comparison to the healthy controls, patients with renal diseases and patients after kidney transplantation had higher concentrations of total plasma homocysteine and its metabolites. Similar results were found for SDMA and ADMA: Patients with chronic renal insufficiency both with and without hemodialysis had significantly higher values than the renal transplant recipients and healthy controls. A clear influence of cigarette smoking on the levels of the laboratory parameters measured could not be determined in any group; neither in the patients with diabetes mellitus, nor in the patients with renal diseases, nor in the healthy controls. CONCLUSIONS: The present trial demonstrates an increase in the parameters linked to the development of cardiovascular diseases including total plasma homocysteine, its metabolites, the dimethylarginines SDMA and ADMA and advanced glycation end-products depending on the degree of renal insufficiency. Moreover, in patients with insulin-treated diabetes mellitus, the concentrations of the AGE-products CML and pentosidine seem to be strongly influenced by the quality of diabetes control and blood pressure levels. There was no influence of cigarette smoking on the levels of the laboratory parameters measured.

Adult↗

PubMed2003

Advanced glycation end-products pentosidine and N epsilon-carboxymethyllysine are elevated in serum of patients with osteoporosis.

OBJECTIVE: To investigate serum levels of the advanced glycation end-products (AGEs) pentosidine and N epsilon-carboxymethyllysine (CML) in patients classified into different osteoporosis subgroups according to histomorphometric data. METHOD: Serum samples were obtained from 116 osteoporotic patients (34 men, 82 women) classified by bone histomorphometry into subgroups with high turnover (HTO, n = 32), low turnover (LTO, n = 39), normal turnover (NTO, n = 9) and cellular uncoupled osteoporosis (CUO, n = 36). Pentosidine was measured by high-performance liquid chromatography, and CML by a competitive enzyme-linked immunoassay. RESULTS: The entire osteoporosis group had significantly higher pentosidine and CML serum concentrations than healthy subjects. In contrast to healthy subjects, no correlation between levels of AGEs and age could be found. In subgroups characterized by increased bone resorption (HTO, CUO), serum pentosidine correlated significantly with the histomorphometric marker reflecting osteoclast activity/bone resorption (eroded surface as a percentage of trabecular surface). Moreover, in CUO a strong correlation between pentosidine and the mineral apposition rate was found. Surprisingly, in HTO the levels of CML and percentage of eroded surface were significantly negatively correlated. CONCLUSION: AGE-modified proteins may be a cause of disturbed bone remodelling in osteoporosis. Our findings do not support the alternative hypothesis that increased AGEs in serum indicate only a more intensive releasing of AGEs in circumstances of increased bone resorption.

Adult↗

PubMed2003

[Validity of iohexol clearance in patients with chronic renal failure and normal renal function in comparison to (99m)Tc-DTPA-clearance].

BACKGROUND AND OBJECTIVE: The most common method used for testing dynamic renal function is creatinine clearance, but it has some limitations, e. g. variable muscle mass and tubular secretion of creatinine. The use of radionuclides as an exact method is limited in terms of availability, cost and time needed for examination. We compared the plasma clearance of iohexol with the established (99m)Tc-diethylenetriaminepentaacetate acid (DTPA) clearance. The aim of the present study was to validate iohexol clearance as a simple and suitable method for measuring to determine GFR with a comparable sensitivity to radioisotopic methods. METHODS: 120 patients (49 females, 71 males), mean age of 56 (range 20 to 84) years with normal renal function and different stages of renal failure, mean creatinine clearance of 61.6 +/- 44,9 (range 1.8 - 181.1) ml/min/1.73 m2 received a bolus injection of 10 ml iohexol, a non-ionic low osmolar x-ray contrast medium. Using the one-compartment model, plasma samples were taken after 150, 240 and 480 minutes. The total plasma disappearance of iohexol was measured by x-ray fluorescence analysis and the clearance was calculated. The (99m)Tc-DTPA clearance was determined in accordance with a standard protocol. RESULTS: A high correlation was found between the clearance of iohexol and (99m)Tc-DTPA (r = 0.95). The average deviation between Iohexol and (99m)Tc-DTPA clearance was 7.4 ml/min/1.73 m2. Allergic and nephrotoxic side effects were not observed. CONCLUSION: Iohexol clearance is a valid method for measuring GFR in patients at any stages of renal failure. It is easy to perform and inexpensive.

Adult↗

PubMed2003

Anti-C1q antibodies and antiendothelial cell antibodies in systemic lupus erythematosus - relationship with disease activity and renal involvement.

The aim of this study was to investigate the relationship between the presence and titre of antibodies against C1q (anti-C1q Ab) and disease activity and renal involvement in patients with systemic lupus erythematosus (SLE). Anti-C1q Ab were measured in 79 patients with SLE (70 women and 9 men; mean age 41.7 years; mean disease duration 8.4 years): 19 patients had active disease with lupus nephritis, 8 active disease without nephritis, 26 inactive disease with nephritis and 26 inactive disease without nephritis. Anti-dsDNA antibodies (EIA and immunofluorescence), antiendothelial cell antibodies (AECA) and complement levels (C3, C4, total haemolytic complement activity) were determined in parallel. Anti-C1q Ab were positive in 49%, anti-dsDNA Ab in 61% and AECA in 19% of the patients, respectively. Significantly higher titres of anti-C1q Ab were found in patients with active disease compared with those with inactive SLE ( P < 0.01). Serum levels of anti-C1q Ab showed a positive correlation with anti-dsDNA Ab and SLEDAI score ( P < 0.01) and a negative correlation with C3 ( P < 0.05), C4 ( P < 0.01) and CH50U ( P < 0.01). The presence of anti-C1q Ab was not different between patients with or without nephritis. In patients with ( P < 0.05) and without nephritis ( P < 0.01) the frequency of anti-C1q Ab was significantly higher in active patients compared with inactive patients. Both anti-C1q and anti-ds-DNA Ab were detectable in 74% of patients with active nephritis but only in 30% of all other patients ( P=0.001). None of the patients with active nephritis was negative for anti-C1q and anti-dsDNA Ab, whereas 37% of the patients without active nephritis were negative for both antibodies ( P < 0.01). Sensitivity, specificity, positive and negative predictive values for active lupus nephritis among SLE patients were 100%, 50%, 51.9% and 100% for anti-dsDNA Ab (EIA) and 74%, 70%, 57% and 89.4% for positive findings of both anti-dsDNA and anti-C1q Ab. The presence and titre of anti-C1q-Ab in SLE are related to disease activity. Absence of anti-dsDNA Ab excludes active nephritis; positive findings of both anti-dsDNA Ab and anti-C1q Ab are of relatively high specificity for active nephritis.

Adolescent↗

PubMed2003

Hydroxypyridinium collagen crosslinks in serum, urine, synovial fluid and synovial tissue in patients with rheumatoid arthritis compared with osteoarthritis.

OBJECTIVE: To investigate the relationship between inflammation markers and content of pyridinium crosslinks in hydrolysates of synovial tissue and to specify the significance of urinary excreted pyridinoline, released primarily from collagen I and II of bone and cartilage, and deoxypyridinoline released especially from collagen I of bone and dentin, dependent on disease activity in rheumatoid arthritis (RA). METHODS: Synovial tissue and fluid from knee endoprosthesis surgery, as well as simultaneously obtained serum and urine, were collected from 12 patients with inactive RA or RA with low disease activity [iRA: C-reactive protein (CRP) <28 mg/l], 10 with active RA (aRA: CRP > or =28 mg/l) and 21 with OA. After preparation of the synovial tissue, including hydrolysis, completely released synovial pyridinoline and deoxypyridinoline crosslinks as well as those from synovial fluid, serum and urine were investigated using a gradient ion-paired reversed-phase HPLC method. Crosslink levels in synovial tissue are expressed as mol/mol collagen, assuming 300 residues of hydroxyproline per collagen molecule, also measured by HPLC. RESULTS: In the synovial tissue of aRA patients we found significantly elevated total pyridinoline concentrations and pyridinoline/deoxypyridinoline (Pyr/Dpyr) quotients compared with the iRA and OA controls, indicating an elevated crosslinking density of mature synovial tissue collagen with increased activity of RA. Pyridinoline levels and the Pyr/Dpyr ratio were correlated with those of urine and with acute-phase reactants in RA patients. Compared with serum crosslink levels, which were unrelated to disease activity, the urinary concentration of pyridinoline was increased by a factor of 2 and showed a simultaneous increase with increasing synovitis. CONCLUSION: Both crosslinking density and degradation of mature collagen from synovial tissue depend on the disease activity in RA. Urinary excretion of associated crosslinks, expressed as the Pyr/Dpyr ratio, correlates with those in synovial tissue and may be confirmed as a marker of synovial tissue collagen degradation. We suggest that increased crosslinking of mature collagen in the synovial tissue of RA is related to an inflammation-dependent regulation of collagen synthesis in activated synovial fibroblasts, in which lysyl oxidase represents the final enzymatic step for crosslinking.

Adult↗

PubMed2003

Serum levels of total homocysteine, homocysteine metabolites and of advanced glycation end-products (AGEs) in patients after renal transplantation.

AIMS: Hyperhomocysteinemia has been described as an independent risk factor for cardiovascular diseases (CVD) influencing patient outcome. Advanced glycation end-products (AGEs) are involved in the pathogenesis of vascular damage in uremia. This study was undertaken to assess whether high serum levels of total homocysteine (tHcy) with its metabolites methylmalonic acid (MMA), methylcitric acid (MCA) and cystathionine (CYSTA) as well as elevated serum concentrations of the AGEs pentosidine and Nepsilon-carboxymethyllysine (CML) are independent risk factors for CVD, left ventricular hypertrophy (LVH) or hypertension as well as kidney dysfunction in renal transplant recipients (RTR). METHODS: Serum levels of tHCy, MMA, MCA and CYSTA were measured by a gas chromatographic-mass spectrometric assay, pentosidine by HPLC and CML using an ELISA assay. RESULTS: All measured parameters were significantly higher in RTRs than in healthy subjects (p < 0.0001). The levels of pentosidine and CML as well as of tHcy and its metabolites correlated significantly with each other, but not with those ofMMA and CYSTA. Significant correlations were also found between pentosidine and tHcy, MMA or MCA as well as between CML, MMA and MCA, respectively. Acute or chronic rejection did not influence these values. No significant differences were observed between patients with or without CVD or with hypertension. In RTRs with LVH, only the tHcy levels were significantly higher than in those RTRs without LVH (p = 0.006). Logistic regression analysis revealed an independent influence of tHcy on the presence of LVH. CONCLUSION: These results may indicate an association between high tHcy values and LVH. Further investigation is needed to determine whether a reduction of tHcy and Hcy metabolites and/or AGE serum concentrations would significantly improve patient outcome after undergoing renal transplantation.

Adult↗

PubMed2002

Identification of the advanced glycation end products N(epsilon)-carboxymethyllysine in the synovial tissue of patients with rheumatoid arthritis.

BACKGROUND: Generation of advanced glycation end products (AGEs) is an inevitable process in vivo and can be accelerated under pathological conditions such as oxidative stress. In serum and synovial fluid of patients with rheumatoid arthritis (RA) raised AGE levels have been found. OBJECTIVE: To determine the presence of N(epsilon)-carboxymethyllysine (CML; marker of oxidative stress) in RA synovial tissue by immunohistology. METHODS: Frozen synovial tissue samples from 10 patients with RA and eight controls (four patients without joint disease and four patients with osteoarthritis (OA)) were treated with rabbit-anti-CML-IgG and goat-antirabbit-IgG. Immunostaining was visualised by streptavidine-alkaline phosphatase (chromogen fuchsin). Cell differentiation was performed with antibodies against CD68, CD45RO, and CD20. RESULTS: CML was detected in the synovial lining, sublining, and endothelium in 10/10 RA and 4/4 OA synovial specimens. In RA some macrophages (CD68+) and T cells (CD45RO+) showed positive immunostaining for CML, whereas B cells were negative. Staining in OA synovial sublining was weak compared with RA. CONCLUSIONS: CML was detected for the first time in RA and OA synovial tissue. Different patterns of immunostaining in RA and OA and the presence of CML on macrophages and T cells, suggest a role for CML in the pathogenesis of RA. This might be due to presentation of new epitopes which can maintain or even trigger an autoimmune response.

Adult↗

PubMed2002

Interleukin 4 co-stimulates the PDGF-BB- and bFGF-mediated proliferation of mesangial cells and myofibroblasts.

BACKGROUND: Although many mediators involved in the pathogenesis of fibrosis are known, its precise mechanism is still unknown. In vitro experiments may contribute to the recognition of cellular changes which also take place during fibrosis. METHODS: Renal tubular epithelial cells (EPC), mesangial cells (MC) and glomerular endothelial cells (GEDC) as well as endothelial cells (EDC) and myofibroblasts (MF) from cattle were isolated to measure the proliferation and protein synthesis in the presence of individual and combined cytokines/growth factors in cell cultures. RESULTS: Cytokines stimulating or permitting the proliferation of myofibroblast-like cells (MFLC) (MC and MF), caused damage of endothelial cells (EDC, GEDC), whereas EPC were stable. The proliferation of MFLC was strongly stimulated by PDGF-BB and bFGF and elevated more than twofold in the presence of interleukin 4 (IL-4), but IL-4 alone had no effect. Furthermore, the proliferation of transdifferentiated endothelial cells (TEC), obtained by incubation of EDC with TNFalpha and bFGF, was stimulated with both PDGF-BB/IL-4 and bFGF/IL-4 in the same way and proved to be stable with respect to TNFalpha. CONCLUSION: Interleukin 4 co-stimulates the PDGF-BB- and bFGF-mediated proliferation of MC, MF, and TEC. TNFalpha does not inhibit the proliferation of extracellular matrix-synthesizing cells, but has an inhibitory or even toxic effect on EDC and GEDC. It may be concluded that cytokines released in inflamed renal tissue influence tubulointerstitial cells in different ways, resulting in progressive tissue damage and fibrosis in which the EDC would be the most sensitive cells. Thus, we speculate that microvascular injury in these areas leads to ischemia and malnutrition of tubular EPC and may be responsible for ongoing tubular damage and resulting renal interstitial fibrosis.

Animals↗

PubMed2002

The effects of prolonged physical exercise on renal function, electrolyte balance and muscle cell breakdown.

BACKGROUND: Postexercise proteinuria, hematuria and changes in serum electrolyte balance as well as increased levels of plasma indicators for muscle leakage are believed to be transient and of benign character. METHODS: A group of 51 healthy athletes took part in a 100 km race over 14.25 hours. All of them had to reach the finish together. Urine and blood samples were collected before (a) and immediately after running (b) as well as 6 hours after the race (c). RESULTS: The serum concentrations of potassium (4.8 +/- 0.5 (a) vs. 4.0 +/- 0.3 (c) mmol/l), protein (73.1 +/- 5.2 (a) vs. 71.1 +/- 3.9 (c) g/l) and albumin (44.0 +/- 2.85 (a) vs. 42.9 +/- 2.8 (c) g/l) decreased significantly (p < 0.0001, p < 0.05, p < 0.05, respectively) but remained within physiological ranges. The serum sodium concentration decreased immediately after the race (136.9 +/- 4.5 (a) vs. 131.1 +/- 2.4 (b) micromol/l, p < 0.0001). The fractional sodium excretion decreased 6 hours, but not immediately after the race (0.78 +/- 0.59 (a) vs. 0.48 +/- 0.82 (c), p < 0.05). Myoglobin (31.8 +/- 6.9 (a), 291.5 +/- 197.2 (b) and 182.2 +/- 135.3 (c) microg/l, p < 0.0001) and creatine kinase (1.13 +/- 0.45 (a), 10.76 +/- 6.9 (b) and 9.46 +/- 15.5 (c) pmol/l, p < 0.0001) increased dramatically. Troponin I was also significantly increased at finish (0.0186 +/- 0.0121 (a) vs. 0.0213 +/- 0.0165 (b) ng/ml, p < 0.05) and positively correlated with myoglobin and creatine kinase, but remained far below the pathologic range. Serum creatinine and urea remained almost unchanged. Glucosuria and hematuria occurred 6 hours after the run in 9.1% and 6.8%, respectively. The erythrocytes examined by phase-contrast microscopy were not damaged in terms of dysmorphic cells. Glomerular-type proteinuria was found in 11.4% of the participants 6 hours after the race. CONCLUSIONS: We conclude that long lasting, mild exertion is harmless for renal function, electrolyte balance and skeletal muscle as well as myocardial metabolism in healthy persons.

Adult↗

PubMed2002

Determination of autofluorescence of red blood cells (RbCs) in uremic patients as a marker of oxidative damage.

AIM: It is suggested that the red blood cells (RBCs) of uremic patients have increased oxidative damage. The activities of different antioxidant enzymes and the levels of several antioxidants or lipid peroxidation products in RBCs are usually determined to estimate the oxidative stress in uremia. The autofluorescence of RBCs as measured by flow cytometry is caused by the formation of conjugated Schiff base compounds from aldehydes derived from lipid peroxidation and amino groups of phospholipids or cell proteins, and has been proposed as a marker of oxidative stress. The aim of this study was to evaluate if this method is suitable for estimation of oxidative stress in the RBCs of patients with different degrees of renal insufficiency. PATIENTS AND METHODS: To determine the oxidative damage in RBCs in uremia, the autofluorescence of RBCs was measured by flow cytometry in the following 3 groups of patients: group A: 16 patients with chronic renal failure (CRF); group B: 16 hemodialysis (HD) patients; group C: 16 patients with a well-functioning renal allograft. Twenty-four healthy volunteers served as controls. The basal value of RBC autofluorescence and the autofluorescence of RBCs after oxidative damage by treatment with 0.1 mM hydrogen peroxide (H2O2)/0.7 mM sodium azide were determined. RESULTS: In basal RBC autofluorescence values, no differences were found between the 3 groups and the controls. However, there was a significant correlation between the increase of serum creatinine and RBC autofluorescence in the group of patients with CRF (r = 0.521; p = 0.038). After H2O2 treatment, the RBC autofluorescence rose markedly in all individuals. This increase in RBC autofluorescence was significantly higher in the patients with CRF (p = 0.003) and in the HD patients (p = 0.001) compared to the controls. In contrast, there was no difference in RBC autofluorescence between the patients with renal allograft and the controls after H2O2 treatment. CONCLUSIONS: In conclusion, flow cytometry is a useful tool for determining oxidative damage in RBCs. The RBCs of uremic patients are more susceptible to oxidative damage induced by H2O2, likely caused by diminished antioxidant defense in the RBC membrane. Successful renal transplantation leads to a normal autofluorescence response in the RBCs after H2O2 treatment.

Aged↗

PubMed2002

Aluminum deposition in the bone of patients with chronic renal failure--detection of aluminum accumulation without signs of aluminum toxicity in bone using acid solochrome azurine.

In this study, the sensitivity of the aurine tricarboxylic acid (ATA) and acid solochrome azurine (ASA) stain for aluminum were compared under special consideration of the relationship to bone histology in renal osteodystrophy. Al deposition in iliac crest bone biopsies taken from 78 patients with chronic renal failure (CRF) was assessed histochemically using the ATA and ASA stain; the Al accumulation was correlated with bone histology and histomorphometry. Significantly more Al was detectable with the ASA method on trabecular bone surfaces and cement lines (18 +/- 20% vs 4 +/- 12% on surfaces; 13 +/- 18% vs 0.4 +/- 1.3% on cement lines). In 31 cases in which ATA yielded negative results, ASA in contrast indicated Al deposits on up to 20% of the trabecular bone surface. The specimens with more Al on the trabecular bone surface had a significantly higher osteoid volume and osteoid surface. With ATA, these differences were observed at a staining of > or = 10% of the trabecular surface, with ASA at a staining of > or = 40% of the trabecular surface. Therefore, it seems to be possible to detect a very low Al deposition, without any Al-induced changes in bone morphology or signs of Al toxicity in the bone using the ASA method. By contrast, a positive ATA stain is mainly found in biopsies with typical signs of Al-induced changes of histomorphometric bone parameters. We, therefore, recommend the routine use of the ASA stain to detect Al deposition in bone.

Adult↗

PubMed2001

Laser-assisted uvulopalatoplasty for snoring: medium- to long-term subjective and objective analysis.

OBJECTIVE: To assess the subjective and objective medium- to long-term results of laser-assisted uvulopalatoplasty for snoring. DESIGN: A nonrandomized, prospective, before-after trial. SUBJECTS AND INTERVENTIONS: Fourteen patients underwent laser-assisted uvulopalatoplasty surgery; 2 surgical techniques, which differ with respect to the mode of midline palatal vaporization, were used. MAIN OUTCOME MEASURES: Subjective analysis included a preoperative and 2 postoperative evaluations of the state of snoring: 4 weeks and 10.1 +/- 7.9 months (mean +/- SD) after completion of last laser treatment. In addition, a score on 5 other sleep-related symptoms was recorded before treatment and after 10.1 +/- 7.9 months; at that time, patients also estimated their overall satisfaction with the procedure. Objective analysis included preoperative nocturnal polysomnographic studies that were repeated postoperatively. RESULTS: A decline in snoring improvement from 79% (11/14) to 57% (8/14) was recorded; furthermore, state of snoring worsened from 7% (1/14) to 21% (3/14). Likewise, reevaluation of the 5 other sleep-related symptoms at the final follow-up visit uncovered a 57% improvement rate. Overall satisfaction with the procedure was 43%. The results of the postoperative objective studies corresponded to those of the subjective ones and demonstrated significant worsening of respiratory disturbance index in 3 (21%) of the 14 patients, who became mildly apneic. These findings were encountered with both laser techniques. CONCLUSIONS: The favorable subjective short-term results of laser-assisted uvulopalatoplasty deteriorated with time. In addition, postoperative nocturnal polysomnography showed that the procedure caused mild obstructive sleep apnea in a considerable number of patients who formerly were nonapneic snorers. These findings may be related to velopharyngeal narrowing and progressive palatal fibrosis, caused by the thermal damage inflicted by the laser beam.

Adult↗

PubMed2001

Clinical manifestation of POEMS syndrome with features of connective tissue disease.

The POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome is a rare plasma cell disease with multiorgan involvement and varying clinical manifestations. We report a 38-year-old man who presented with scleroderma-like skin changes of the hands and feet, sicca and Raynaud's syndrome, pleural effusions, glomerulopathy, polyneuropathy, hepatosplenomegaly and lymphadenopathy. Steroid treatment was started on the assumption of a connective tissue disease and led to a temporary improvement. During the further course of the disease, hypothyreosis, monoclonal gammopathy and osteosclerotic bone lesions were detected, leading to the diagnosis of POEMS syndrome. This case emphasises the need to consider POEMS syndrome as a differential diagnosis in patients with signs of connective tissue disease and polyneuropathy.

Adult↗

PubMed2001

[Rare association of acute febrile neutrophilic dermatosis (Sweet syndrome) with rheumatoid arthritis].

We report on a 57 year old women with a long-standing course of severe rheumatoid arthritis, developing acute febrile neutrophilic dermatosis (Sweet's syndrome) in an active phase of the arthritis. Sweet's syndrome has been reported with hematologic and solid malignancies, infections and several autoimmunopathies, but in only three cases is there a coincidence with rheumatoid arthritis. We review Sweet's syndrome with regard to pathogenesis and associated disorders.

Arthritis, Rheumatoid↗