PubMed Health⌕ Search

Biomedical subjects

S Heidenreich

Publications and source records attributed to S Heidenreich.

At least 19 recordsLinked to original sources
PubMed2003

Calcineurin-free protocols with basiliximab induction allow patients included in "old to old" programs achieve standard kidney transplant function.

INTRODUCTION: The EuroTransplant "old to old" program establishes that patients older than 60 years can receive offers of organs from donors older than 60 years. The compromised function of these organs makes it a priority to preserve their initial kidney function. HYPOTHESIS: Calcineurin-sparing protocols using anti-IL-2 receptor (IL-2R) antibody induction (Simulect) may benefit initial kidney function in these patients, as assessed by the rates of delayed graft function and of rejection during the first month after transplant. PATIENTS AND METHODS: A cohort of 15 consecutive elderly patients were prospectively compared with 30 cadaveric kidney transplants in younger recipients. Study patients were induced with Simulect (20 mg, 30 minutes before reperfusion and 4 days after transplantation) and steroids, delaying the introduction of CsA until the serum creatinine was below 3 mg/dL. The other cohort of patients were immunosuppressed with tacrolimus (trough 8 to 12), mycophenolats mofetil (MMF, 1 g/d), and an identical taper of steroids. The analysis compared donor and recipient ages, mean cold ischemic time, incidence of initial kidney function (diuresis in the first 24 h) serum creatinine levels, glomerular filtration rate (GFR), number of dialysis sessions, and rejection rate in the two groups. RESULTS: Except for the donor and recipient ages (72 vs 54 in donors, and 67 versus 52 years in recipients), no significant differences were observed between the groups among the rates of acute rejection (6.6% vs 13.2%), delayed graft function (13.2% required dialysis), or infection (6.6%). Within 1 month all 45 grafts showed primary function with equal creatinine levels (mean 1.65). CONCLUSIONS: Calcineurin-free protocols using IL-2 therapy as the initial suppression allow patients in the "old to old" ET program to display equal results to cadaveric kidney transplants with initial treatment with calcineurin antagonists.

Adrenal Cortex Hormones↗
PubMed2003

Living donor kidney transplantation: chance for the recipient--financial risk for the donor?

BACKGROUND: With living donation, in addition to the medical risk, the financial risk for the donor is essential, especially in case of complications that potentially can led to disability and loss of work. We report the experiences of those who have donated a kidney in our transplant center. METHODS: We contacted 80 donors who donated a kidney at least 6 months prior to evaluation: 72% answered 33 questions. [mean age: 54 +/- 10 (33-75) years; 69% living related, 31% unrelated]. RESULTS: Of the 80 donors contacted, 91% (53) reported to have no financial expenses due to donation; 9% (5) had expenses, but only few of them clarified exact amount. One donor had to borrow money to cover the lack when he was unable to perform his job. Another claimed the disparity between normal salary and payment from insurance company as a financial expense. Evaluation procedure prior to donation was organized variously: some donors were on holiday while evaluated, some officially were ill, others had to take off some days without payment. None of the donors lost his or her job due to donation. CONCLUSION: The financial risk of living donation is theoretically well covered by different insurances. However, some of the donors had to cover some expenses by themselves. Fortunately, so far in our center no major complications occurred and all donors went home in good health after donation. If costs are covered when a healthy donor loses his or her ability to work due to donation remains unclear since no donor has experienced this problem.

Follow-Up Studies↗
PubMed2003

Arterial hypertension and ischaemic stroke.

OBJECTIVES: Arterial hypertension is, besides age, the number one risk factor for ischaemic stroke. Patients with arterial hypertension frequently present with additional coexisting vascular risk factors interacting in a complex way. MATERIAL AND METHODS: This paper reviews the benefit of antihypertensive treatment, as well as different treatment options of arterial hypertension and their side-effects. RESULTS: Patients with definite arterial hypertension, but also patients with so-called normal or high-normal blood pressure are at increased risk to develop stroke and other cardiovascular complications. Vascular remodelling of small and large vessels provoked by arterial hypertension is the initial step in the development of atherosclerosis and lipohyalinosis. Vascular remodelling can be improved or even normalized by antihypertensive treatment with angiotensin-converting-enzyme inhibitors and angiotensin-I-receptor antagonists showing the most convincing effects. Angiotensin-converting-enzyme inhibitors and angiotensin-I-receptor antagonists have the lowest rate of side-effects, however, economic restraints hinder their general application. Statins are needed to treat dyslipidaemia. They also lower blood pressure and have a synergistic effect with the above two antihypertensive components in lowering blood pressure. In hypertensive patients, risk of stroke and other cardiovascular complications is determined by the blood pressure level and the presence or absence of target organ damage and the interaction with other risk factors, such as cigarette smoking, dyslipidaemia, and diabetes. These high-risk patients should be treated even more aggressively than usual. CONCLUSIONS: In the vast majority of patients and healthy individuals, target blood pressure should be as high as or below 120/80 mmHg to minimize the occurrence of stroke and other cardiovascular complications.

Angiotensin Receptor Antagonists↗
PubMed2001

The anastomosis between renal polar arteries and arteria epigastrica inferior in kidney transplantation: an option to decrease the risk of ureter necrosis?

Ureteral necrosis after renal transplantation is often the result of impaired perfusion due to loss of donor polar arteries. A way of preserving polar arteries is their anastomosis with the A. epigastrica inferior. In three cases (aged 49-, 58-, and 63 years), 9.3 % of 33 living donors, we detected donor polar arteries on both sides, and anastomosed the polar artery to the A. epigastrica inferior with microsurgical methods. Intraoperatively, the flow was measured by flowmeter, in the postoperative course duplexsonography and MR-angiography was performed. In all three cases we noted a bluish, ischemic parenchym mass of 10-25 % of the kidney and ureter. It recovered immediately, however, after the polar artery had been reconstructed. Intraoperative measurement showed a high flow on the polar- and the main renal artery. Duplexsonography and MR-angiography documented a good flow on the A. epigastrica anastomosis. There have been no signs of ureteral problems at all. After a mean follow-up time of 26 months, the mean creatinine level is 1.46 mg/ml. Ureteral necrosis after kidney transplantation is mostly the result of a lack of perfusion of the polar arteries of the lower kidney pole. If arteriosclerotic lesions inhibit an anastomosis with the renal artery, the anastomosis with the A. epigastrica inferior seems to be a useful alternative.

Anastomosis, Surgical↗
PubMed2001

Attention deficits in minimal hepatic encephalopathy.

Minimal hepatic encephalopathy (HE) is characterized by a decrease of psychomotor speed, and deficits in visual perception, visuo-spatial orientation, and visuo-constructive abilities. Attention deficits have also been proposed to be part of the syndrome. Several attempts were made in the past to elaborate suitable psychometric means for the assessment of minimal HE. However, there is still no "gold standard" for the diagnosis of minimal HE. We recently evaluated the so called "PSE-Test" for the assessment of minimal HE, a test battery which does not include a test predominantly aimed at the assessment of attention. We therefore presented a battery of attention tests in addition to the PSE-Test to a group of cirrhotics without clinical signs of HE compared to a healthy control group matched for age and education to determine whether the addition of special attention tests would increase the diagnostic sensitivity of the PSE-Test. It was shown that the patients with a pathological PSE-Test result differed significantly from controls in all attention tests applied, while the patients with normal PSE-Test results achieved attention test results similar to that of the controls. Thus, the PSE-Test results represent attention deficits as well as deficits in motor skills, visuo-spatial orientation, and visual construction.

Adult↗
PubMed2001

Effect of fluvastatin on endothelium-dependent brachial artery vasodilation in patients after renal transplantation.

BACKGROUND: Hypercholesterolemia may affect both endothelial function and arterial distensibility (DC). Renal transplant recipients (NTX) exhibit advanced structural and functional alterations of arterial vessel walls. The aim of this double-blind, randomized trial was to evaluate the effects of fluvastatin (FLU) on brachial artery flow-mediated vasodilation (FMD) and DC in hypercholesterolemic NTX. METHODS: Eighteen NTX received FLU 40 mg/day and 18 NTX placebo (PLA). Before and after six months of treatment, the brachial artery diameter and DC at rest were measured by a Doppler frequency analysis in the M mode, and then changes in diameter during reactive hyperemia (to assess endothelial-dependent FMD) and after 400 microg sublingual nitroglycerin (to assess endothelium-independent vasodilation-NMD). RESULTS: FLU, but not PLA, treatment resulted in significant decreases in total (from 288 +/- 10 to 239 +/- 8 mg/dL, P < 0.05) and low-density lipoprotein cholesterol (from 182 +/- 779 to 138 +/- 8 mg/dL, P < 0.05). Blood pressure did not differ between FLU- and PLA-treated patients and was not affected by either treatment. Also, the brachial artery baseline diameter was not different between groups and was not affected by FLU or PLA. Brachial artery flow at rest and during reactive hyperemia as measured by pulsed Doppler did not differ between groups. Brachial artery FMD increased with FLU from 0.23 +/- 0.08 to 0.54 +/- 0.08 mm (P < 0.05), whereas PLA did not alter FMD (0.22 +/- 0.07 vs. 0.14 +/- 0.05 mm at baseline and after six months of PLA treatment, respectively, P = NS). In contrast, NMD did not change significantly with either treatment (0.76 +/- 0.13 vs. 0.83 +/- 0.15 mm at baseline and after 6 months of FLU treatment, respectively, P = NS, and 0.64 +/- 0.09 vs. 0.66 +/- 0.10 mm at baseline and after 6 months of PLA treatment, respectively, P = NS). Also, brachial artery DC was not altered by FLU (6.4 +/- 1.0 vs. 5.8 +/- 0.6 x 10-3/kPa, P = NS) or PLA treatment (5.8 +/- 0.6 vs. 6.8 +/- 0.8 x 10-3/kPa, P = NS). CONCLUSIONS: In hypercholesterolemic NTX, the HMG-CoA reductase inhibitor FLU significantly improves brachial artery FMD as a measure of endothelial function after six months of treatment. In contrast, FLU does not have a beneficial effect on brachial artery DC.

Brachial Artery↗
PubMed2000

Cadaveric "two-in-one" kidney transplantation from marginal donors: experience of 26 cases after 3 years.

BACKGROUND: Because of the problem of organ shortage, the use of renal transplants from marginal donors has been tested by different procedures. METHODS: In our center 26 recipients (59 +/- 7 years) underwent double renal transplantation from July 1996 to August 1999 using marginal donors (71 +/- 6 years). A special scoring was applied that included donor age, serum creatinine, the grade of glomerulosclerosis, and kidney weights leading to the decision whether single or dual or no kidney transplantation was performed. RESULTS: After an average follow-up of 18 +/- 10 months 22 of 26 (85%) double kidney transplant recipients are alive and have functioning grafts. Three patients died with well-functioning grafts. The actuarial 1-year patient and graft survival rate was 94% (n=18), the 2-year rate 92% (n=12). Two patients lost one graft each without becoming dialysis dependent. The average serum creatinine was 1.6 +/- 0.5 mg/dl after 12 months (n=17) and 1.9 +/- 0.6 mg/dl after 24 months (n=11). Primary nonfunction occurred in 31%, acute rejection within the first 6 months in 14%. Ten patients who received single old grafts according to our score had similar transplant survival rates but worse graft function after 1 year. CONCLUSIONS: Transplant function and survival of patients after dual kidney transplantation indicate that this procedure is reasonable to ameliorate the problem of organ shortage. The most crucial point is to establish a widely accepted standardized scoring for the donors leading to single, dual, or refusal of transplantation.

Aged↗
PubMed2000

[Long-term problems after kidney transplantations].

Allogenic kidney transplantation is a widely established treatment option for patients with end-stage renal disease to gain independency from dialysis and recovery of excretory and hormonal functions. Transplantation is superior to dialysis with respect to quality of life, morbidity and mortality. Improvements in one-year graft survival have become evident during the last decades, but long-term outcome is not yet satisfying. The most common form of late transplant failure is chronic rejection or chronic allograft nephropathy, and as a consequence of higher ages of transplant recipients death of patients with functioning grafts. The histological hallmark of chronic rejection is intimal thickening of small arteries and arterioles, but the involved pathomechanisms are not well understood. Strict normalization of blood pressure and hyperlipidemia by drugs aims to prevent vascular alterations of chronic allograft nephropathy. In addition, in this overview some other late complications of renal transplant recipients are addressed which are associated to chronic immunosuppression, such as viral or malignant diseases.

Age Factors↗
PubMed2000

Pulmonary manifestation of systemic mast cell disease.

Systemic mast cell disease is a rare disease of unknown aetiology. Systemic infiltration and proliferation of mast cells in skin, bone marrow, gastrointestinum and lymph nodes is the central pathological feature. This study reports a patient with mastocytosis of the skin (urticaria pigmentosa) for 10 yrs. The patient was referred to hospital for dyspnoea. Chest radiograph showed moderate reticular infiltration of both lungs, computerized tomography revealed multiple lymph nodes of the mediastinum and faint nodular lesions of middle and upper areas of lungs. Transbronchial biopsy demonstrated mast cell infiltration of the lung with formation of mast cell granuloma. According to the current literature, systemic mast cell disease with pulmonary involvement is a very rare entity. After a treatment with interferon alpha-2a over 6 months, the patient's condition and particularly dyspnoea showed improvement in parallel with an amelioration of the lesions as demonstrated by thorax computed tomography.

Humans↗
PubMed2000

Regulation of mesangial cell apoptosis and proliferation by intracellular Ca(2+) signals.

BACKGROUND: In inflammatory glomerular diseases, proliferation, as well as apoptosis of mesangial cells (MCs), has been shown histomorphologically. Both processes may regulate the cellular content of the mesangium by closely influencing each other. In the present study, we examined whether the cytoplasmic free Ca(2+) concentration [Ca(2+)](i) is involved as a key second messenger in the regulation of proliferative and apoptotic events. METHODS: Thapsigargin, an inhibitor of the endoplasmic Ca(2+)-Mg(2+)-ATPase, was used as a test substance to investigate the role of [Ca(2+)](i) in signaling MC apoptosis and growth in vitro. Apoptosis was determined by nuclear chromatin staining with Hoechst 33258, by a [3H]-thymidine-based DNA fragmentation assay or by flow cytometry detecting binding of FITC-conjugated annexin V. Proliferation was measured by [3H]-thymidine incorporation into acid-precipitable material and corroborated by cell counting. RESULTS: Thapsigargin significantly induced apoptosis and inhibited proliferation dose dependently in nanomolar concentrations without evoking necrotic damage when administered not longer than 12 hours. Significant apoptosis was measurable after a six-hour treatment of MCs with thapsigargin. Determination of [Ca(2+)](i) by fura-2-dependent spectrofluorometry showed that thapsigargin was able to induce prolonged [Ca(2+)](i) rises that could be prevented by preincubation with the intracellular Ca(2+) chelator 1, 2-bis(2-aminophenoxy)-ethane-N,N,N', N'-tetra-acetic acid (BAPTA) acetomethyl ester (AM). BAPTA had no influence on MC viability but reversed thapsigargin-induced apoptosis to control levels. After thapsigargin treatment (100 nmol/L, 12 hours), apoptotic MCs had a significantly higher [Ca(2+)](i) of 251 +/- 25 nmol/L (N = 41) as compared with MCs that were not or not yet apoptotic ([Ca(2+)](i) of 116 +/- 20 nmol/L, N = 26, P < 0,05). Platelet-derived growth factor (PDGF), a well-characterized growth factor for MCs, reversed the effects of thapsigargin on proliferation and apoptosis in a similar fashion as BAPTA. PDGF acutely stimulated increases of [Ca2+]i but abolished thapsigargin-dependent, but not angiotensin II- or ATP-induced Ca(2+) rises when administered during a 12-hour preincubation. CONCLUSIONS: Our data suggest that a sustained increase of [Ca(2+)](i) may serve as a signal to trigger MC apoptosis. Growth factors such as PDGF can abolish apoptosis induced by elevations of [Ca(2+)](i) by altering intracellular Ca(2+) signaling.

Animals↗
PubMed2000

Differential expression of heat shock protein 70 (hsp70) in human monocytes rendered apoptotic by IL-4 or serum deprivation.

Apoptosis of monocytes is regulated by the balance between pro- and antiapoptotic triggers and pathways and may strongly influence inflammatory disorders. The major heat shock protein, hsp70, is an effective inhibitor of apoptosis in lymphocytic and monocytic tumor cell lines, but the implications in the regulation of apoptosis of freshly isolated human monocytes have not been elucidated. In this study, we examined whether two different triggers of monocyte apoptosis, serum deprivation and IL-4, respectively, altered hsp70 expression and whether expression levels correlated with monocyte survival. Monocyte apoptosis was determined quantitatively by flow cytometry detecting annexin V binding or nuclear stainability with propidium iodide (PI). Hsp70 expression was analyzed by semiquantitative RT-PCR and immunoblotting. Exposing monocytes to heat shock (47 degrees C, 20 min) induced a rapid and marked upregulation of hsp70 without evoking injury or apoptosis, suggesting that hsp70 conferred protection and survival. In accordance, when monocytes were rendered apoptotic by serum deprivation, a drastic downregulation of hsp70 occurred, which was accompanied by a reduced synthesis of the constitutive family member hsc70. However, induction of monocyte apoptosis by IL-4 increased hsp70 expression in a concentration and time-dependent fashion. A neutralizing antibody against IL-4 abolished hsp70 expression and apoptosis induction after IL-4 treatment and so excluded indirect effects. LPS rescued monocytes from apoptosis but did not alter hsp70 formation significantly. These findings suggest that, in monocytes, distinct apoptotic triggers induce different responses of hsp70 so that this molecule does not exert protection against cell death directly or in general.

Antibodies↗
PubMed1999

Prognostic value of lymphocyte apoptosis in acute rejection of renal allografts.

BACKGROUND: Apoptosis is a cellular phenomenon generally found within rejecting transplants. It may play a role in physiological or therapy-associated deletion of infiltrating lymphocytes or in graft cell destruction. Our study focuses on apoptosis of infiltrating lymphocytes during acute kidney rejection after the initial steroid pulse therapy and on possible prognostic implications. METHODS: Renal biopsy specimens of 23 transplant recipients with acute tubulo-interstitial rejection were examined for appearance of apoptosis and compared with 11 transplant biopsies with unspecific organ injury accompanied by lymphocyte infiltration. In all patients, biopsies were performed after steroid pulse therapy, and, after confirmation of rejection, antilymphocytic antibody treatment was carried out. Apoptosis was determined via terminal deoxynucleotidyltransferase-mediated dUTP-digoxigenin nick end labeling analysis and confirmed by electron microscopy. RESULTS: Apoptosis of lymphocytes or of tubular epithelium was detected in 11 cases of acute rejection (48%), respectively. Four biopsies showed lymphocytic as well as tubular apoptosis, whereas five sections showed no signs of programmed cell death. In biopsies revealing unspecific injury, tubular cell apoptosis was more frequently found (73%) compared with lymphocyte apoptosis (27%, P<0.05). Most interestingly, patients with a beneficial recovery from acute rejection had a higher proportion of lymphocyte apoptosis compared with patients with poor rejection outcome. The Bcl-2 oncoprotein was widely found within infiltrating lymphocytes without counter-regulating apoptosis. CONCLUSIONS: Lymphocyte apoptosis is found as frequently as tubular cell apoptosis in rejecting renal grafts after steroid pulse therapy and might have prognostic value for rejection outcome.

Acute Disease↗
PubMed1999

Monocyte CD14: a multifunctional receptor engaged in apoptosis from both sides.

Like all other immune system cells, monocytes and macrophages may undergo apoptotic cell death in response to specific triggers and mediators or as a consequence of aging. However, factors inducing apoptosis and the involved cellular and molecular mechanisms are much better investigated and understood for lymphocytes. Th2 cell-derived cytokines such as interleukin-4 (IL-4) are able to induce monocyte apoptosis most effectively. This process is preceded by down-regulation of the CD14 surface receptor. Mediators such as lipopolysaccharide (LPS) suppress and postpone apoptosis in parallel with up-regulation of CD14. Macrophages are rather resistant against apoptotic damage, and factors able to evoke apoptosis in monocytes are often ineffective in macrophages. Resistance of macrophages against apoptotic triggers may be beneficial for inflammatory processes where macrophages are engaged and needed as phagocytes for ingestion and removal of moribund cells. The multifunctional CD14 receptor of monocytes/macrophages is supposed to be involved in the apoptotic network on both sides: as a surface molecule of monocytes that can promote survival and antagonize apoptosis and as a recognition receptor of macrophages that enables or supports interaction with apoptotic cells.

Apoptosis↗
PubMed1999

How to assess glomerular function and damage in humans.

In human subjects, the assessment of renal function and of its changes by interventions is limited to the measurement of glomerular filtration rate (GFR), renal blood flow and the estimation of proteinuria. In humans, GFR can be determined exactly by measuring the clearance of an ideal filtration marker, such as inulin. The classic method of measuring inulin clearance in humans includes constant intravenous infusion of the compound and timed collections of urine. In order to avoid the need for timed urine collections, a number of alternative procedures have been devised. All these methods only use determinations of inulin in plasma or serum. From these, the total body inulin clearance is obtained using pharmacokinetic calculations. In order to measure total body clearance, usually called plasma clearance, inulin is either given as a constant intravenous infusion or as a bolus infusion. Both procedures overestimate GFR because of incomplete distribution of inulin during the study periods. The error may be minimized by using model-independent pharmacokinetic calculations. Unlike inulin, creatinine is not a perfect filtration marker. This is because the substance is not only eliminated by glomerular filtration but also by tubular secretion. The extent of tubular creatinine secretion is not constant in various individuals. Serum creatinine concentration is a commonly used measure of renal function in clinical practice. This parameter is determined both by the renal elimination and by the production of the compound. Differences in creatinine production among subjects and over time in a single individual may occur because of changes in muscle mass. Radioisotopic filtration markers can easily and accurately be measured in plasma and serum. Using this method, the plasma concentration-time curve of these compounds can easily be studied after intravenous bolus injection. From the plasma concentration-time curves obtained, the total body clearance (plasma clearance) of the substances can be calculated using pharmacokinetic models. Most frequently, 125l-iothalamate, 99mTc-diethylenethiaminepenta-acetic acid and 51Cr-ethylenediaminetetra-acetic acid are used for the estimation of GFR in humans. The total body clearance of all these filtration markers overestimates GFR. The error induced by this phenomenon is particularly relevant at low levels of GFR. In recent years, iohexol has been used as a filtration marker. The substance can be measured in plasma, serum and urine using high-performance liquid chromatography. So far, good agreement has been shown for GFR determined by the classic inulin clearance and by the iohexol plasma clearance. Screening for proteinuria is commonly performed using reagent test strips. Quantitative measurements of marker proteins can be used to estimate the extent and the site of damage in the nephron. These measurements may be used to estimate the progression of renal disease and the response to therapeutic interventions. Of particular interest is the degree of albuminuria which indicates nephropathy in diabetic patients and end-organ damage in patients with hypertension.

Humans↗