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Biomedical subjects

G Sunder-Plassmann

Publications and source records attributed to G Sunder-Plassmann.

At least 91 records · Page 5Linked to original sources
PubMed1997

Safety aspects of parenteral iron in patients with end-stage renal disease.

Absolute and functional iron deficiency is the most common cause of epoetin (recombinant human erythropoietin) hyporesponsiveness in renal failure patients. Diagnostic procedures for determining iron deficiency include measurement of serum iron levels, serum ferritin levels, saturation of transferrin and percentage of hypochromic red blood cells. Patients with iron deficiency should receive supplemental iron, either orally or intravenously. Adequate intravenous iron supplementation allows reduction of epoetin dosage by approximately 40%. Intravenous iron supplementation is recommended for all patients undergoing haemodialysis and for pre-dialysis and peritoneal dialysis patients with severe iron deficiency. During the maintenance phase (period of epoetin therapy after correction of iron deficiency), the use of low-dose intravenous iron supplementation (10 to 20 mg per haemodialysis treatment or 100 mg every second week) avoids iron overtreatment and minimises potential adverse effects. Depending on the degree of pre-existing iron deficiency, markedly higher iron doses are necessary during the correction phase (period of epoetin therapy after correction of iron deficiency) [e.g. intravenous iron 40 to 100 mg per haemodialysis session up to a total dose of 1000 mg]. The iron status should be monitored monthly during the correction phase and every 3 months during the maintenance phase to avoid overtreatment with intravenous iron.

Anemia, Iron-Deficiency↗
PubMed1997

Erythropoietin and iron.

Careful evaluation of iron status is of pivotal importance in end-stage renal disease patients before and during r-HuEPO therapy. Absolute (ferritin < 100 micrograms/l) and functional (ferritin normal or supranormal, transferrin saturation < 20%, hypochromic red blood cell [RBC] > 5%) iron deficiency are the main reasons for r-HuEPO hyporesponsiveness. Adequate iron supplementation allows significant reduction of r-HuEPO dosage and costs. Oral iron supplementation is recommended for predialysis and peritoneal dialysis patients with serum ferritin > 100 micrograms/l, whereas i.v. iron supplementation is the therapy of choice in hemodialysis patients. However, neutrophil impairment and other possible side-effects (e.g. cardiovascular complications, malignancy) as a result of i.v. iron therapy suggest that overtreatment with i.v. iron should be avoided.

Aluminum↗
PubMed1996

Alternative puncture site for implantable permanent haemodialysis catheters.

BACKGROUND: Vascular access represents a major problem in long-term haemodialysis patients. In patients without patent internal arteriovenous fistula, the implantation of cuffed catheters to provide a temporary or permanent central venous access is often necessary. Catheterization of the subclavian vein should be avoided because of the high risk of stenosis or thrombosis. The puncture of the internal jugular vein can be impossible in cases with stenosis or thrombosis due to previous catheterization. To overcome these limitations we evaluated an alternative puncture site for implantation of permanent central venous catheters. METHODS: The very low, most central jugular approach, first described by Rao et al., with the site of puncture just above the medial notch of the clavicle, was used to introduce Dacron cuffed dialysis catheters into the innominate vein in four chronic dialysis patients with impeded conventional vascular access. RESULTS: In all four patients puncture of the internal jugular vein using Rao's technique was successful at the first attempt. All four catheters were introduced without any problems. Even in a case with thrombosis of the internal jugular vein and the ipsilateral subclavian vein, this technique was successfully applied. No complications such as haematoma, pneumothorax, or catheter-associated infection were observed. The catheters remained in situ for 2-12 months with excellent blood flow and without clinical evidence of venous stenosis or thrombosis. CONCLUSIONS: In case of failure to cannulate the internal jugular vein by a conventional approach, the technique of Rao et al. can be used before sacrificing the subclavian vein or changing to exotic techniques such as translumbar, transfemoral or transhepatic methods.

Adult↗
PubMed1996

Resistance to activated protein C (APC): mutation at Arg506 of coagulation factor V and vascular access thrombosis in haemodialysis patients.

BACKGROUND: Vascular access thrombosis represents a serious problem in haemodialysis patients. Therefore identification of relevant thrombotic risk factors is clinically valuable. Resistance to activated protein C (APC) was recently identified as a new thrombophilic defect which is caused by a single point mutation in the factor V gene. Whether this mutation predisposes to vascular access thrombosis is unknown. METHODS: The presence of factor V Leiden (mutation at nucleotide position 1691 of the factor V gene) was determined by polymerase chain reaction (PCR) analysis in 152 haemodialysis patients from all three haemodialysis units of the University Hospital of Vienna. In 61 patients (54 without mutation, 7 with heterozygous mutation) resistance to APC was evaluated. One hundred-seven individuals without renal failure (57 negative for factor V Leiden, 50 heterozygous subjects) served as controls. Haemodialysis patients with heterozygous factor V Leiden mutation were carefully investigated for thrombotic complications of vascular access, other thromboembolic events and additional putative thromboembolic risk factors. RESULTS: Seven of 152 (4.6%) patients were heterozygous carriers of factor V Leiden. The mean APC resistance ration in heterozygous dialysis patients was 2.31; in the 50 heterozygous controls the ratio was 2.02. The mean APC ratio in haemodialysis patients without mutation was 3.53 in contrast to 2.95 in the control group. Not one of the seven heterozygous haemodialysis patients suffered from vascular access thrombosis of inexplicable origin. Three patients remained totally free of access thrombosis from onset of haemodialysis treatment. In four of seven patients nine events of thrombosis of the vascular access occurred, but were due to anatomical stenosis in each case. In six permanent central venous catheters no episode of occlusion or reduced blood flow requiring thrombolytic therapy was observed. Family history with regard to thrombotic events was negative in all seven patients. No thromboembolic complication occurred during 13 periods of immobilization, in the course of six pregnancies and during oral contraception. CONCLUSIONS: The heterozygous carrier status for factor V Leiden does not appear to represent a risk factor for vascular access thrombosis in haemodialysis patients. This is possibly due to the fact that the functional APC activity is high and in heterozygous haemodialysis patients APC resistance ratios are very close to the normal range. However, it cannot be excluded that a homozygous factor V mutation represents an increased risk for shunt thrombosis. Therefore patients suffering from repeated and/or inexplicable shunt thrombosis should be tested for the factor V mutation to evaluate the effect of a homozygous mutation.

Adult↗
PubMed1996

Secondary migration: a complication of Hickman central venous catheters.

We report two patients with spontaneous intrajugular migration of Hickman catheters which were initially correctly placed with the tip in the right atrium, via the right subclavian vein. In one patient the catheter remained in situ for 40 days without any sequelae; in the second patient the catheter was removed immediately. In the first patient two interim chest radiographs disclosed the catheter's course suggesting a possible mechanism of migration. Since early detection of this complication allows interventional repositioning, periodic monitoring of indwelling catheters by chest X-ray is recommended.

Adult↗
PubMed1996

Safety of intravenous injection of iron saccharate in haemodialysis patients.

BACKGROUND: The most frequent i.v. iron preparations used for haemodialysis patients are iron dextran, iron gluconate and iron saccharate. Possible side effects include anaphylactic reactions due to preformed antibodies to dextran or vascular reactions due to unbound iron during treatment with iron gluconate or iron saccharate. METHODS: Four dosage regimens of i.v. iron saccharate therapy were studied: 10, 20, 40 and 100 mg, which were given over a time period of 1 min after the end of the dialysis session. Iron metabolism parameters (serum iron concentrations, transferrin saturation and serum ferritin levels) were measured at 0, 1, 5, 15 and 30 min after application and immediately prior to the next dialysis session. All 18 regular haemodialysis patients studied received recombinant human erythropoietin (rHuEpo). RESULTS: Serum iron levels and transferrin saturation increased significantly following i.v. injection of all doses of iron saccharate. Iron 'oversaturation' of transferrin iron binding did not occur in patients with transferrin levels > 180 mg/dl. However, in patients with transferrin levels < 180 mg/dl the injection of 100 mg iron saccharate resulted in a transferrin saturation of 102.6 +/- 39.5% (two patients with transferrin levels of 87 and 92 mg/dl had transferrin saturation of 119.8 and 149.7%, two patients with transferrin levels of 148 and 171 mg/dl had transferrin saturations of 77.9 and 63.1%, respectively). Serum ferritin levels remained unchanged during the post-injection period and increased by the next dialysis session following injection of 100 mg iron saccharate by 165%. CONCLUSION: It is concluded that intravenous iron saccharate injection (10-100 mg even within 1 min) does not result in 'oversaturation' of transferrin iron binding if serum transferrin levels are > 180 mg/dl (high-risk patients; transferrin < 100 mg/dl). This may explain, at least in part, the minimal side effects observed during the i.v. application of iron saccharate. Low-dose i.v. iron saccharate (10-40 mg) is recommended for iron supplementation of haemodialysis patients. If injection of 100 mg is necessary, serum transferrin level should exceed 180 mg/dl. There is, however, no need for fast i.v. injection during routine iron supplementation.

Adult↗
PubMed1995

HBV and HCV genome in peripheral blood mononuclear cells in patients undergoing chronic hemodialysis.

Patients undergoing chronic hemodialysis are at risk for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). As peripheral blood mononuclear cells (PMNC) are known to be susceptible to infection of both HBV and HCV, assessment of viral genomes in those cells could uncover occult infections not detected by serologic methods or virus determination in serum. We investigated all 67 patients undergoing chronic hemodialysis at a single dialysis unit by PCR for the presence of HBV or HCV genomes in serum as well as in PMNC. None of the 67 patients was HBsAg positive or showed HBV-DNA in serum, but in 5 patients HBV-DNA in PMNC was detected as the only marker of HBV-infection; those patients were also anti-HBc negative. In 9 patients HCV-RNA was positive in serum; in 5 of those patients it was also found in PMNC. Three of these infected patients were negative for anti-HCV. One other patient had no anti-HCV or HCV-RNA in serum, but was positive for HCV-RNA in PMNC. Thus, in 6 patients (8.9%) undergoing chronic hemodialysis we found evidence of infection with HBV or HCV by detecting viral genomes in PMNC without the presence of viremia, antigenemia or specific viral antibodies in serum. The detection of viral genomes in PMNC could be useful in the positive identification of additional potentially infectious patients.

Adult↗
PubMed1995

Importance of iron supply for erythropoietin therapy.

BACKGROUND: rHuEpo and iron therapy corrects renal anaemia. However, dosage, route of administration, and monitoring of iron and rHuEpo therapy in uraemic patients remains controversial. METHODS: Therefore a 22-month i.v. iron substitution trial, subdivided into four study periods, was initiated in 64 iron-depleted chronic haemodialysis (HD) patients receiving i.v. rHuEpo therapy. Within the first period (6 months) patients were treated with high-dose iron (100 mg at the end of HD treatment, mean cumulative i.v. iron saccharate dosage was 2538 +/- 810 mg per patient) in order to replete the iron stores. During the 2nd period (6 months) the available iron pool was maintained with low-dose iron by administration of 10, 20, or 40 mg iron at each HD, depending on haemoglobin, serum ferritin and transferrin saturation levels. During the 3rd period (4 months), the iron-replete patients were randomized to i.v. or s.c. route of rHuEpo administration. During the 4th period (3 months) iron substitution was omitted to exclude severe iron overload. RESULTS: In the first study period, high-dose iron therapy dramatically reduced the weekly rHuEpo requirement by 70% of the initial dose (from 217 +/- 179 to 62.6 +/- 70.2 U/kg/week). In the 2nd period iron storage pools were easily maintained. Serum ferritin and transferrin saturation levels remained stable during this study period. Randomization for thrice-weekly i.v. or s.c. administration of rHuEpo in the 3rd study period revealed comparable efficacy for both administration routes in iron-replete patients. In well-nourished patients (serum albumin > 40 g/l) without hyperparathyroidism (parathyroid hormone levels < 100 pg/ml), 50-60 U/kg/week rHuEpo were required in contrast to > 100 U/kg/week in patients with hyperparathyroidism. In the 4th study period, withdrawal of iron administration led to a rapid decrease of serum ferritin and transferrin saturation levels, indicating the absence of severe iron overload. CONCLUSIONS: Long-term thrice-weekly i.v. low-dose iron therapy (10-20 mg per HD treatment) proved to be a very effective, economical and safe treatment schedule for iron-replete HD patients. Intravenous and s.c. rHuEpo therapy was equally efficacious in iron-replete, well-nourished patients. HD patients with increased parathyroid hormone levels require significantly more rHuEpo than HD patients with parathyroid hormone levels values < 100 pg/ml).

Drug Administration Routes↗
PubMed1994

Functional characterization of cytokine autoantibodies in chronic renal failure patients.

We have recently reported on an increase of IL-1 alpha and IL-6 autoantibodies in patients maintained on chronic hemodialysis treatment. The aim of the present study was to evaluate functional properties of these autoantibodies. Serum samples of more then 500 chronic renal failure patients with and without replacement therapy were screened for the presence of IL-1 alpha and IL-6 autoantibodies by second antibody precipitation. The neutralizing capacity of IL-1 alpha autoantibody serum was studied by immunofluorescence flow cytometry analysis of IL-1 alpha induced expression of E-selectin (ELAM-1, CD62e) on HUVEC (human umbilical vein endothelial cells). Results of these inhibition studies were confirmed with IgG preparations from antibody positive sera, purified by affinity chromatography. Functional studies on IL-6-dependent B9 cell proliferation were performed with IL-6 autoantibody positive sera, and quantitated with the colorimetric MTT assay. IL-1 alpha induced expression of E-selectin on HUVEC (considered 100% positive cells) was inhibited by each IL-1 alpha autoantibody positive serum sample (N = 13; anti-IL-1 alpha activity: 7.62 to 57.52% binding). Inhibition of E-selectin expression by IL-1 alpha autoantibodies ranged from 0.11 to 80.22% positive cells (0.15 to 92.31% mean fluorescence intensity). A strong correlation of E-selectin expression with IL-1 alpha autoantibody concentration was observed (P < 0.005). Furthermore, IgG eluates from autoantibody positive patients inhibited E-selectin expression to 41.0 +/- 23.1% positive cells if compared with 83.7 +/- 5.7% positive cells of the IgG depleted serum samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1994

Iron metabolism and iron substitution during erythropoietin therapy.

Anemia is rapidly corrected by r-HuEPO in the majority of patients with end-stage renal disease provided that iron stores are carefully assessed. Serum ferritin, transferrin saturation and hypochromic red cells are parameters in evaluating the patients' iron status. Replenishment of diminished iron stores may be achieved using oral or intravenous iron. Vigorous iron substitution in r-HuEPO treated patients seems to be mandatory concerning public economy. The intravenous route is the way of choice in delivering sufficient iron supplementation not only in patients felt to be insensitive to standard r-HuEPO dose in therapy. The strategy for the most effective preservation of the iron storage pool and the optimal parameters for monitoring iron demand remains to be elucidated.

Anemia↗
PubMed1993

In vivo and in vitro primed lymphocytes. Correlation of cytochemically detected BLT-specific lymphoid serine protease with cytotoxic activity.

We describe the validation of a cytochemical method to detect a cytolytic cell-specific lymphoid serine protease which can be upregulated during viral infection and allogeneic stimulation. The cytolytic cell specificity was ascertained by demonstrating a high correlation between BLT substrate-specific serine protease (SP) activity and cytotoxicity of in vivo and in vitro stimulated lymphocytes. The presence of SP in peripheral blood lymphocytes was compared with their capacity to kill K562 targets in a lectin-dependent cytotoxicity assay. The correlation coefficient was 0.92 and 0.93 at E:T ratios 10:1 and 20:1 respectively. In allogeneic mixed lymphocyte cultures an increase of SP activity in effector lymphocytes was paralleled by an augmentation of cytotoxic capacity towards stimulator target cells. SP+ granules showed intracellular polarization to the effector/target cell interface during conjugate formation. These results together with previous studies suggest that this method provides a sensitive assay which predicts the cytolytic potential present in a lymphocyte population.

CD4-Positive T-Lymphocytes↗