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Biomedical subjects

H Holzer

Publications and source records attributed to H Holzer.

At least 19 recordsLinked to original sources
PubMed2006

Changes in total parathyroid hormone (PTH), PTH-(1-84) and large C-PTH fragments in different stages of chronic kidney disease.

INTRODUCTION: Loss of renal function is accompanied by progressive increase in serum levels of intact parathyroid hormone (iPTH) in patients with end-stage renal disease (ESRD). There is a paucity of data regarding levels of PTH-(1-84) and its large carboxyl-terminal fragments (large C-PTH fragments) and progressive loss of kidney function in patients with chronic kidney disease (CKD). The current study was undertaken to describe the glomerular filtration rate (GFR)-dependent plasma concentrations of PTH-(1-84) and related large C-PTH fragments in adult patients with CKD by using different commercially available PTH assays. METHODS: We studied 80 Caucasian patients with CKD stages 1-5 without renal replacement therapy. Creatinine clearance was calculated by the Modification of Diet in Renal Disease (MDRD) formula. Levels of iPTH were determined by second-generation assays (iPTH Elecsys system, Roche Diagnostics; DUO total iPTH, Scantibodies Laboratory, Inc.; iPTH, Nichols Institute Diagnostics). Third-generation assays were used to measure PTH-(1-84) (CAP (cyclase activating PTH), Scantibodies; Bio-Intact PTH, Nichols). Levels of large C-PTH fragments and ratios of PTH-(1-84)/large C-PTH fragments were calculated and statistical analyses performed. RESULTS: Levels of iPTH and PTH-(1-84) showed CKD stage-dependent increases. Variations among the assays increased with progressive loss of kidney function. The assay from Scantibodies showed a GFR-dependent decrease of the ratio 1-84 PTH / large C-PTH fragment that was not observed with the Nichols assay. CONCLUSION: Increasing variations among the assays with progression of CKD emphasize the fact that the interpretation of measurements must take into consideration the specific assay. We found evidence for a possible preferential increase of the level of large C-PTH fragments over 1-84 PTH in a CKD stage-dependent manner (Scantibodies). The clinical implications of this finding have to be further evaluated by bone biopsy studies.

Adult↗
PubMed2006

[Assisted reproduction technologies and the risk of fetal, chromosomal and genetic malformations].

BACKGROUND: Assisted reproduction techniques allowed thousands of otherwise infertile couples to attain pregnancy. As this technology moves into the mainstream of infertility treatment, it has become more critical to reassess its safety. OBJECTIVE: To review the birth outcome of patients undergoing conventional in-vitro fertilization and intracyto- plasmic sperm injection regarding fetal malformations, chromosomal and genetic abnormalities. METHODS: Selective review of the literature. RESULTS: Most of the published data is from observational studies and is not randomized or blinded. Unfortunately, most articles are inherently biased. Chromosomal and genetic abnormalities are increased probably only as a direct corollary to the underlying parental risk and not due to the technology itself. There is a slight increase in the congenital malformations rate, but inspection of these malformations reveal no clustering of any specific abnormality. CONCLUSIONS: Children born after assisted reproduction technologies have an increased risk of a major congenital malformation and chromosomal abnormalities compared with those born after natural conception. The risk is mainly due to paternal and maternal risk factors, which are more prevalent in couples who use assisted reproduction techniques for reproduction. Infertility-linked risk is highly probable for the observed findings. A technique-related risk, however, cannot be ruled out. Intracytoplasmic sperm injection appears to be a safe alternative for couples who otherwise would be unable to achieve pregnancy. The inherent risks associated with these genetically "at risk" couples mandate thorough evaluation and counseling before undertaking ICSI.

Congenital Abnormalities↗
PubMed2006

Long-term administration of enteric-coated mycophenolate sodium (EC-MPS; myfortic) is safe in kidney transplant patients.

BACKGROUND: To date, there are no data on long-term use of enteric-coated mycophenolate sodium (EC-MPS; myfortic) from time of renal transplantation. We report the first long-term safety and efficacy data on EC-MPS when administered for up to 3 years post transplant. METHODS: De novo renal transplant recipients completing 1 year of treatment in a multicenter, randomized, double-blind trial of EC-MPS versus mycophenolate mofetil (MMF) were invited to take part in an open-label extension during which all patients received EC-MPS 720 mg b.i.d. Results from the period 12 - 36 months post transplant were compared to comparable data from MMF-treated patients taking part in two studies of everolimus versus MMF (RAD 201 and RAD 251). RESULTS: Of 367 patients completing the blinded core study, 247(62%) entered the open-label extension phase. During the first 24 months of the extension, the incidence, type and severity of adverse events were comparable between the newly-exposed and long-term EC-MPS patients. There were 2 deaths in the newly-exposed group and 4 among long-term EC-MPS patients, with 1 and 2 graft losses, respectively. Six patients (5%) in the newly-exposed group and 4 (3%) in the long-term EC-MPS group experienced biopsy-proven acute rejection. Cross-study comparisons indicated that the tolerability profile of EC-MPS was similar to MMF, including the incidence of adverse events, infections and malignancies, as was the incidence of efficacy events. CONCLUSION: These results demonstrate that EC-MPS with cyclosporine and steroids provides good long-term efficacy and tolerability, and confirm the safety of converting renal transplant patients from MMF to EC-MPS.

Adolescent↗
PubMed2005

Human placental Hofbauer cells express sprouty proteins: a possible modulating mechanism of villous branching.

The development of the chorionic villous tree into a complex and organized ramified tubular network can be termed branching morphogenesis. Studying the molecular mechanisms involved in this process may contribute to the understanding of pregnancy complications such as preeclampsia. Sprouty (Spry) proteins are important regulators of branching morphogenesis and growth factor signaling. We analyzed the expression of Spry genes in human placenta. RT-PCR and immunohistochemistry were employed to detect placental Spry expression. Quantitative RT-PCR was used to assess the effect of FGF and reduced oxygen fraction on Spry gene expression. Spry 1, 2 and 3 expression was observed in placental tissue from all three trimesters. Our results reveal for the first time that Spry proteins are localized in the stroma of the chorionic villi, adjacent to cytotrophoblasts in areas of villous sprouting. Immunofluorescent double staining with anti-Spry and anti-CD68 confirmed that placental macrophages (Hofbauer cells) express Spry. Reduced oxygen fraction, FGF-4 and FGF-10 stimulated Spry-2 expression. Hofbauer cells also expressed c-Cbl, a protein that interacts with Spry. Placental expression of Spry and c-Cbl implies an important role for Hofbauer cells in placental development, possibly through a mesenchymal-epithelial interaction with trophoblasts. Regulation of Spry-2 expression by FGF-4 and FGF-10 suggests an orchestrated regulatory system that modulates villous branching.

Cells, Cultured↗
PubMed2004

Long-term comparison of a calcium-free phosphate binder and calcium carbonate--phosphorus metabolism and cardiovascular calcification.

BACKGROUND: Calcium carbonate used as a phosphate binder may contribute to cardiovascular calcification. Long-term comparisons of sevelamer, a non-calcium polymeric phosphate binder, and calcium carbonate (CC) are lacking. METHODS: 114 adult hemodialysis patients were randomly assigned to open label sevelamer or CC for 52 weeks. Study efficacy endpoints included changes in serum phosphorus, calcium, calcium-phosphorus product, and lipids. In addition, initial and sequential electron beam computerized tomography scans were performed to assess cardiovascular calcification status and change during follow-up. Safety endpoints were serum biochemistry, blood cell counts and adverse events. RESULTS: Patients receiving sevelamer had a similar reduction in serum phosphorus as patients receiving CC (sevelamer -0.58 +/- 0.68 mmol/l, CC -0.52 +/- 0.50 mmol/l; p = 0.62). Reductions in calcium-phosphorus product were not significantly different (sevelamer -1.4 +/- 1.7 mmol2/l2, CC -0.9 +/- 1.2 mmol2/l2; p = 0.12). CC produced significantly more hypercalcemia (> 2.8 mmol/l in 0% sevelamer and 19% CC patients, p < 0.01) and suppressed intact parathyroid hormone below 150 pg/ml in the majority of patients. Sevelamer patients experienced significant (p < 0.01) reductions in total (-1.2 +/- 0.9 mmol/l, -24%) and LDL cholesterol (-1.2 +/- 0.9 mmol/l, -30%). CC patients had significant increases in coronary artery (median +34%, p < 0.01) and aortic calcification (median +32%, p < 0.01) that were not observed in sevelamer-treated patients. Patients on sevelamer required more grams of binder (sevelamer 5.9 g vs. CC 3.9 g) and experienced more dyspepsia than patients on calcium carbonate. CONCLUSIONS: Sevelamer is an effective phosphate binder that unlike calcium carbonate is not associated with progressive cardiovascular calcification in hemodialysis patients.

Adult↗
PubMed2003

[Dialock--an alternative to Permcath and access graft].

PURPOSE: An adequate vascular access is the precondition for a well-functioning hemodialysis. Due to the increasing age and the rising co-morbidity of hemodialysis patients the number of those with grafts or central venous catheters (CVC) is steadily growing. The Dialock vascular access system provides a subcutaneously implantable device for hemodialysis that combines the advantages of central venous access with percutaneous puncture. PATIENTS AND METHODS: Over a period of 30 months 26 Dialock vascular access systems were implanted at our department. 17 patients were male, 9 patients female. In 11 patients the implantation of this system was indicated for internal medicine reasons. In 15 long-term hemodialysis patients implantation was carried out as ultimate solution because of persisting vascular access problems. In a comparable control group of 22 hemodialysis patients 47 vascular accesses were registered within the same period. In parallel, another 110 patients with grafts implanted at our department at that time but not put to hemodialysis at our clinic were analysed. RESULTS: In a comparable number of access days the graft and the central venous catheter showed a considerably higher infection rate (Exit site + blood stream infection) per 1,000 hemodialysis access days than the vascular access device. The rate of malfunctions with or without subsequent lysis was higher using the CVC than when applying Dialock or graft. Angiographies with percutaneous transluminal angioplasty (PTA), or thrombectomies, respectively were significantly more often required with the graft than changes of catheter when using the vascular access system. More than half of the 110 patients observed at the same time, who had a graft implanted at our department without subsequent hemodialysis at our clinic had to undergo another surgical or radiologic intervention. CONCLUSION: The Dialock access system represents in our experience a safe and with careful application less complicated vascular access device for the complex hemodialysis patient. With comparatively low infection and complication rates the Dialock vascular access system serves as a good alternative to the permanent CVC (Permcath) as well as to the graft.

Adult↗
PubMed2001

Ex vivo low-density lipoprotein oxidizability and in vivo lipid peroxidation in patients on CAPD.

BACKGROUND: Chronic renal failure is associated with accelerated atherosclerosis and a high incidence of cardiovascular disease. Oxidative modification of low-density lipoprotein (LDL) is considered a key event in atherogenesis. METHODS: We studied the ex vivo oxidizability of LDL exposed to Cu2+ ions (lag time, rate of propagation, maximum conjugated diene formation) and its relationship with LDL density, fatty acids, and antioxidants, along with plasma malondialdehyde (MDA) and autoantibodies against Cu2+-, MDA-, and hypochlorous acid-modified LDL and plasma antioxidants in 17 continuous ambulatory peritoneal dialysis (CAPD) patients and 21 healthy control subjects. RESULTS: LDL alpha- and gamma-tocopherol and total polyunsaturated fatty acid (PUFA) concentrations were significantly higher in the CAPD patients. LDL density was shifted to small, dense LDL. LDL oxidizability was comparable to that of healthy subjects. Lag time correlated positively with LDL alpha-tocopherol and inversely with both total PUFA concentrations and density; the rate of oxidation and LDL density correlated positively with total PUFA and total fatty acid concentrations, respectively. Ratios of autoantibody titers against oxidized to native LDL did not differ between the two groups. While plasma alpha- and gamma-tocopherol concentrations and tocopherol to cholesterol ratios were significantly higher, vitamin C concentrations were very low in the CAPD patients. MDA concentrations were 1.7 times higher than in healthy subjects. CONCLUSIONS: (1) Ex vivo LDL oxidizability is normal in CAPD patients as a result of efficient protection by LDL-associated lipophilic antioxidants, although the LDL composition is altered toward high oxidizability; and (2) the plasma antioxidant screen is insufficient due to impaired vitamin C status.

Adult↗
PubMed2001

Effect of cyclosporine withdrawal on mycophenolic acid pharmacokinetics in kidney transplant recipients with deteriorating renal function: preliminary report.

Mycophenolic acid (MPA) concentrations are lower in transplant recipients receiving mycophenolate mofetil (MMF) and cyclosporine compared with MMF with tacrolimus. It is not clear whether this is due to an effect of cyclosporin or tacrolimus on MPA pharmacokinetics. To study this effect, kidney transplant recipients with deteriorating renal function (n = 5) receiving cyclosporin and steroids were given mycophenolate mofetil over 4 weeks during a run-in phase (1 g/d in week 1, 1.5 g/d in week 2, 2 g/d starting from week 3). From week 5 the cyclosporin dose was reduced, and it was completely withdrawn at week 10. Creatinine, MPA, and MPA glucuronide metabolites (MPAG, AcMPAG) were determined before (week 4) and after (week 11 and week 32) cyclosporin was withdrawn. Cyclosporin withdrawal was associated with increased MPA areas under the curve (AUCs) and predose concentrations in four of the five patients. In contrast, MPAG and AcMPAG AUCs as well as predose MPAG concentrations significantly decreased. Six months after cyclosporin withdrawal, MPA AUC and predose values tended to return to initial values, whereas metabolite concentrations remained low. Cyclosporin discontinuation caused an acute increase in MPA exposure and a concomitant reduction in metabolite concentrations. The results are consistent with the hypothesis that cyclosporin attenuates the enterohepatic recirculation of MPAG/MPA.

Adult↗
PubMed2000

Access recirculation in a native fistula in spite of a seemingly adequate access flow.

True access recirculation (AR) measured by ultrasound dilution technique is usually absent in well-working shunts. It occurs with low access flows (Qa). High access flow rates are assumed to prevent AR. Two major exceptions to these rules are known: presence of intra-access strictures and inadvertently reversed blood lines. We present an additional exception in which true access recirculation occurred in a native arteriovenous (AV) fistula with correct placement of bloodlines. Surprisingly, access blood flow exceeded pump blood flow (Qb) almost threefold. The situation was clarified by a magnetic resonance angiogram showing a collateral forming a functional loop. This loop led to true access recirculation in one branch, although overall blood flow through both branches appeared to be adequate. The different findings in this shunt over time give insight into the often complex pathophysiology of native fistulae. This case proves that seemingly adequate access flow does not necessarily prevent access recirculation in native AV fistulae. We suggest monitoring both access flow and recirculation in hemodialysis accesses on a regular basis.

Adult↗
PubMed2000

Dynamic renal function testing by compartmental analysis: assessment of renal functional reserve in essential hypertension.

BACKGROUND: In essential hypertension, acute haemodynamic changes due to dietary protein load cause patterns of acute changes in renal function that are fundamentally different from changes in normal controls. METHODS: Renal clearances of sinistrin, an inulin-like polyfructosan, and p-aminohippurate were determined before and after protein ingestion. These tests were performed in healthy controls and in patients with essential hypertension (mean arterial pressure of 112+/-2 mmHg, age, 52+/-2 years; mean+/-SEM) within a washout period, and after long-term treatment with carvedilol and fosinopril, respectively. RESULTS: In 15 healthy volunteers, protein ingestion increased glomerular filtration rate (GFR) from 110.3+/-3.6 to 120. 6+/-4.4 ml/min (P=0.0006; two-tailed pairwise t-test). In contrast, it led to an acute decrease in GFR in 16 hypertensive patients, from 111.8+/-2.9 to 103.6+/-3.3 ml/min (P=0.0010). The eight patients who were randomized to receive carvedilol improved in their renal response to protein (GFR increased from 101.4+/-6.4 to 107.1+/-5.4 ml/min; P=0.04), whereas the eight other patients randomized to receive fosinopril exhibited no change in GFR (final value 105+/-4.9 ml/min). In the patients, the acute shifts in renal plasma flows were not significant. Mean arterial blood pressure of the patients decreased from 112+/-2 to 100+/-3 mmHg (P=0.0015). CONCLUSIONS: In essential hypertension an acute protein load induces a decrease in GFR that may normalize under antihypertensive treatment. The acute changes in GFR can be reliably monitored by the here-described compartmental analysis method of renal functional reserve.

Adult↗
PubMed1999

[Treatment of longitudinal femoropopliteal vascular lesions with stents--report of individual cases].

PURPOSE: In a retrospective analysis the results of stent implantation in the superficial femoral and popliteal arteries were analysed. The stenoses were all larger than 10 cm in length. PATIENTS AND METHODS: In 16 patients (3 women, 13 men, mean age 74 years) 15 occlusions and 2 stenoses (average lesion length 13.9 cm) in the superficial femoral and popliteal arteries were treated with stents. Prior to treatment, 11 patients were in clinical stage 2 b, 1 in stage 3, and 5 in stage 4 according to Fontaine. In 15 cases a wall stent was implanted and in 2 a wall stent combined with a nitinol stent since a wall stent of ideal length was not available. The patients received heparin through a venous lock during the operation and as infusion for 24 hours after the operation, as well as ticlopidine for 4 weeks and acetylsalicylic acid as long-term medication. RESULTS: All 17 lesions were recanalized without residual stenoses. After stent implantation the arterial system was completely restored in 3 limbs, 8 patients were in stage 1, 2 in stage 2 a, 2 in stage 2 b, and 1 still in stage 4 according to Fontaine. 8 patients suffered from a stent thrombosis (within 1 week, after 3 weeks, and after 3 months). 4 stents were treated by angioplasty 4 and 5 months after implantation for suspected intimal hyperplasia. According to Kaplan-Meier the primary patency rate after 12 months was 85% (+/- 12 SD), the secondary rate 76% (+/- 10 SD). CONCLUSIONS: The primary treatment of longer femoropopliteal lesions with stents does not result in a satisfactory primary patency rate. The patency rate after 1 year can be increased to 76% by strict monitoring and reintervention. The method may be recommended, albeit with limitations, for patients in whom a bypass operation is not possible or not desired.

Aged↗
PubMed1999

Preparation of a stable fresh frozen primary lipoprotein[a] (Lp[a]) standard.

LP[a] is one of the most atherogenic lipoproteins consisting of an LDL-like core particle and a covalently linked glycoprotein of variable size. Due to its structural features, its heterogeneity and instability, there are great difficulties in standardizing quantitative immunochemical Lp[a] assays. One particular problem is the preparation of a pure primary standard, which is sufficiently stable to be used for value assignment of secondary reference material. Here we describe a method to purify Lp[a] to virtual homogeneity. When mixed with glycerol at a ratio of 1:1, the preparation is stable in the deep frozen state for more than 12 months. This latter material gave dose;-response curves in several immunochemical assays that were parallel to fresh or frozen sera, freshly prepared Lp[a], and other proposed reference materials. After determination of the protein content by amino acid analysis, it was possible to assign concentrations in molar and mass units to these preparations considering the theoretical molecular weights of the particular apo[a] isoform. Thus we propose to use this procedure for preparation of a "gold standard" for Lp[a] assays.

Cryopreservation↗