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Biomedical subjects

G Sunder-Plassmann

Publications and source records attributed to G Sunder-Plassmann.

At least 73 records · Page 4Linked to original sources

Routine fluoroscopic guidance is not required for placement of Hickman catheters via the supraclavicular route.

The purpose of this study was to evaluate the efficacy and safety in placement of Hickman catheters via the supraclavicular route without fluoroscopic guidance. We studied 81 consecutive percutaneous placements of dual lumen Hickman catheters via the supraclavicular route without the use of fluoroscopic guidance. Success rates, technical problems, complications, infections and reasons for explantation were recorded prospectively. Seventy-nine punctures were successful (97.5%). One pneumothorax (1.2%) and three accidental arterial punctures (3.7%) occurred. Difficulties in introducing the catheter through the peel away sheath or misplacement were not observed. The catheters remained in place for a total of 7657 days (mean 94.5, range 3-392 days). Sixteen blood cultures were positive (2.1/1000 catheter days). Five catheters (6.1%) were lost because of mechanical complications. Forty-two lines (52%) were removed electively, 23 (28.4%) because of suspected infection, and two (2.5%) because of tunnel infection. Nine patients died with a functioning catheter. We conclude that the supraclavicular approach to the subclavian vein is safe and efficient for introduction of Hickman catheters. Using this access, routine fluoroscopic or sonographic guidance is not required for proper placement. Implantation of the lines in an intensive care unit did not lead to higher infection rates than those reported in the literature.

Arteries↗

Mutations in the carboxy terminus of the beta and gamma subunits of the epithelial sodium channel are not present in patients with hypertensive crisis.

BACKGROUND: The pathophysiology of hypertensive crises is poorly understood. To date, no information is available about genetic determinants underlying the individual risk for development of hypertensive urgencies or emergencies. Recently, mutations in the beta subunit (h beta ENaC) and the gamma subunit (h gamma ENaC) of the human epithelial sodium channel (hENaC) have been shown to result in excessive elevation of blood pressure in patients with Liddle's syndrome. METHODS: Using polymerase chain reaction and direct sequencing of amplification products we have screened 90 consecutive out-patients with hypertensive urgency or hypertensive emergency for the presence of mutations in the carboxy terminus of these genes. Furthermore, serum potassium concentrations were determined in all 90 patients, and serum aldosterone levels and plasma renin activity were measured in a subset of 34 patients. RESULTS: Among 71 patients with hypertensive urgency (78.9%) and 19 patients with hypertensive emergency (21.1%) not one individual showed a mutation in genomic DNA extending from codon 532 to codon 637 of h beta ENaC and from codon 525 to codon 651 of h gamma ENaC. Twelve of 90 patients showed mild hypokalaemia (13.3%), 16 of 34 patients had a plasma renin activity below the lower normal range (47.1%) and one of 34 patients had a low serum aldosterone concentration (2.9%). CONCLUSIONS: The present study clearly demonstrates the absence of mutations in the carboxy terminus of the h beta ENaC and h gamma ENaC gene of hENaC in an Austrian cohort of 90 patients suffering from hypertensive crisis.

Adult↗

Endothelial cell adhesion molecule and PMNL response to inflammatory stimuli and AGE-modified fibronectin.

BACKGROUND: Atherosclerotic vascular disease is the leading cause of death in patients with diabetes mellitus and end-stage renal disease. Advanced glycation end products (AGEs) are strongly suggested to be involved in the pathogenesis of atherosclerosis in these patients who also frequently experience infectious complications. We hypothesized that the interaction of AGEs and inflammatory mediators contributes to the up-regulation of endothelial cell activation. METHODS: We investigated the effect of advanced glycated fibronectin in the presence or absence of inflammatory stimuli on the endothelial cell surface and mRNA expression of cell adhesion molecules. Furthermore, the influence of advanced glycated fibronectin on the transendothelial migration pattern of polymorphonuclear cells was analyzed. RESULTS: Exposure to advanced glycated fibronectin together with inflammatory stimuli such as interleukin (IL)-1alpha, tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS) led to a significant increase in the surface expression of the cell adhesion molecules E-selectin, ICAM-1, VCAM-1 and PECAM-1 on endothelial cells. Soluble AGEs in combination with advanced glycated fibronectin significantly enhanced the endothelial cell surface expression of ICAM-1, VCAM-1 and PECAM-1, whereas this was not the case for E-selectin. At the transcriptional level short-time exposure of endothelial cells to advanced glycated fibronectin and inflammatory mediators resulted in an increased expression of E-selectin, ICAM-1 and VCAM-1 mRNA levels, whereas PECAM-1 repeatedly showed a significant decrease of gene transcript levels. An increase of mRNA levels was also observed for E-selectin, ICAM-1, VCAM-1 and PECAM-1 following incubation with a combination of advanced glycated fibronectin and soluble advanced glycation end-products. Furthermore, polymorphonuclear cells responded with a sevenfold increase in transendothelial migration following exposure of endothelial cells to advanced glycated fibronectin and inflammatory mediators. CONCLUSIONS: These results suggest that the combination of matrix glycation and inflammation up-regulates the activation of the endothelial cell adhesion cascade, a mechanism that might contribute to the increased burden of atherosclerotic morbidity and mortality in patients suffering from diabetes mellitus or chronic renal failure.

Albumins↗

GBV-C/HGV in hemodialysis patients: anti-E2 antibodies and GBV-C/HGV-RNA in serum and peripheral blood mononuclear cells.

Hepatitis G virus (GBV-C/HGV), a recently identified RNA virus adds to the risk of parenteral transmitted viral infections in hemodialysis patients. We studied the prevalence of GBV-C/HGV-RNA in serum and peripheral blood mononuclear cells (PMNC) by reverse transcription-polymerase chain reaction (RT-PCR) and determined antibodies against the envelope protein E2 of GBV-C/HGV by ELISA. A total of 119 dialysis patients were studied. GBV-C/HGV-RNA was found in 16 of 119 patients (13%) as compared with 2% of healthy controls (P = 0.014). Two of the 16 GBV-C/HGV-RNA+ patients were co-infected with HCV, and none was positive for HBV-DNA. In 38% of serum GBV-C/HGV-RNA+ patients GBV-C/HGV-RNA was also detected in PMNC. In addition, GBV-C/ HGV-RNA was identified in PMNC of 2 patients negative for GBV-C/ HGV-RNA in serum. Twenty-four patients had anti-E2 antibodies in serum (20%), but were GBV-C/HGV-RNA-. In addition, two of the 16 GBV-C/HGV-RNA+ patients were concomitantly positive for anti-E2 antibodies. Only one of the 16 GBV-C/HGV infected patients had elevated aminotransferases; this patient was co-infected with hepatitis C virus. GBV-C/HGV-RNA positivity was independent on duration of hemodialysis, but GBV-C/HGV-RNA+ patients had received more units of blood in the past. Combined data of past contact, as assessed by anti-E2 antibodies, and present infection, documented by GBV-C/HGV-RNA, indicate a high overall exposure to GBV-C/HGV in dialysis patients.

Adult↗

Major determinants of hyperhomocysteinemia in peritoneal dialysis patients.

The mechanisms leading to elevated total homocysteine concentrations in peritoneal dialysis patients are only partially understood. We show that a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T transition) results in increased total homocysteine levels in peritoneal dialysis patients compared to age- and sex-matched healthy individuals. The allelic frequency of the C677T transition in the MTHFR gene in peritoneal dialysis patients (0.29) was comparable to the frequency in healthy individuals (0.34). Separate comparison of the total homocysteine plasma levels between non-carriers of the MTHFR polymorphism (C/C), heterozygous (C/T) and homozygous (T/T) subjects was performed by analysis of covariance in the patient and the control group. In the patient group the mean total homocysteine level was 61.7 +/- 40.1 mumol/liter in individuals with the (T/T) genotype, which was significantly higher than the total homocysteine concentration of 23.1 +/- 15.8 mumol/liter in (C/T) patients and 22.2 +/- 11.1 mumol/liter for non-carriers (P = 0.0001). Vitamin B12 (P = 0.0001), folate (P = 0.0005), serum creatinine (P = 0.016), albumin (P = 0.0157) and dialysis center (P = 0.0173) significantly influenced total homocysteine plasma levels in peritoneal dialysis patients, whereas this was not the case for age, gender, weekly Kt/V, weekly creatinine clearance, residual renal function, duration of dialysis, mode of peritoneal dialysis and vitamin intake. Folate levels in peritoneal dialysis patients were significantly affected by the MTHFR genotype (P = 0.016). Elevated total homocysteine levels in diabetic patients with cardiovascular disease were associated with increased cardiovascular morbidity. In summary, the present study provides evidence that homozygosity for the C677T transition in the MTHFR gene, low vitamin B12 and low folate levels result in elevated total homocysteine levels in peritoneal dialysis patients.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

Single-dose pharmacokinetics of meropenem during continuous venovenous hemofiltration.

The pharmacokinetic properties of meropenem were investigated in nine critically ill patients treated by continuous venovenous hemofiltration (CVVH). All patients received one dose of 1 g of meropenem intravenously. High-flux polysulfone membranes were used as dialyzers. Meropenem levels were measured in plasma and ultrafiltrate by high-performance liquid chromatography. The total body clearance and elimination half-life were 143.7 +/- 18.6 ml/min and 2.46 +/- 0.41 h, respectively. The post- to prehemofiltration ratio of meropenem was 0.24 +/- 0.06. Peak plasma drug concentrations measured 60 min postinfusion were 28.1 +/- 2.7 microgram/ml, and trough levels after 6 h of CVVH were 6.6 +/- 1.5 microgram/ml. The calculated total daily meropenem requirement in these patients with acute renal failure and undergoing CVVH was 2,482 +/- 321 mg. Based on these data, we conclude that patients with severe infections who are undergoing CVVH can be treated effectively with 1 g of meropenem every 8 h.

Aged↗

Neutrophil impairment associated with iron therapy in hemodialysis patients with functional iron deficiency.

Hemodialysis patients treated with recombinant human erythropoietin (rhEPO) need adequate iron supplementation to avoid rhEPO hyporesponsiveness due to iron deficiency. Low serum ferritin reflects absolute iron deficiency, whereas normal or high ferritin values in combination with low transferrin saturation (< 20%) indicate functional iron deficiency. In this study, healthy subjects (group I) were compared with intravenous (i.v.) rhEPO-treated and i.v. iron-saccharate-treated regular hemodialysis patients that were subdivided into three groups as follows: patients with serum ferritin > 100 and < 350 micrograms/L (group II), patients with ferritin < 60 micrograms/L (group III), and patients with ferritin > 650 micrograms/L but transferrin saturation < 20% (group IV). Polymorphonuclear leukocyte (PMNL) parameters (phagocytosis, intracellular killing of bacteria, oxidative metabolism, glucose uptake, intracellular calcium) for each group were compared with those of multitransfused, iron-overloaded primary hematologic patients (group V) and those of patients suffering from hereditary hemochromatosis (group VI). Compared with PMNL obtained from healthy subjects (group I), group II hemodialysis patients showed mild inhibition of phagocytosis but significant inhibition of intracellular killing of bacteria. Oxidative burst of PMNL from group II patients was also significantly reduced after stimulation in vitro. These dysfunctions were not affected by absolute iron deficiency (comparable data in group III patients). However, impairment of PMNL was markedly aggravated in group IV patients. Intracellular calcium concentration under basal conditions and after stimulation was not different. These data suggest that iron is responsible for the PMNL dysfunctions observed in group IV patients. The PMNL defect of group IV patients was comparable to group V and group VI patients with normal renal function, suggesting again a direct inhibitory effect of iron. It is concluded that hemodialysis patients with high ferritin but low serum iron and low transferrin saturation ("functional iron deficiency") display a significant impairment of fundamental PMNL functions during i.v. iron and rhEPO therapy. This may result in increased risk of infectious complications. Therefore, overtreatment of hemodialysis patients with i.v. iron should be avoided.

Adult↗

Malposition of central venous catheters. Incidence, management and preventive practices.

INTRODUCTION: Proper placement is an essential prerequisite for the use of central venous catheters. Our study was undertaken to determine the incidence of aberrant locations dependent on different anatomic approaches for various types of central venous catheters and to elucidate failures and pitfalls of preventive practices. METHODS: 2580 percutaneously inserted lines (including 538 tunneled devices and 112 implantable Port-A-Caths) introduced by Seldinger's technique were reviewed for inadvertent malpositioning. RESULTS: Primary misplacement was evident on 47 occasions (1.82%), 38 times into large venous tributaries of the superior vena cava. 3 aberrant locations involved a persistent left superior vena cava, two catheters were placed into minor intrathoracic veins and in 3 patients inadvertent arterial cannulation occurred. The frequency of malpositioning was related to the anatomic approach and the catheter type used, but not to the physician's experience. Respective incidences were 4.12% for the left internal jugular access, but were lower for the right internal jugular (1.1%) and the right (1.01%) and left (0.89%) supraclavicular approach. Misplacement was more frequent with soft silicone catheters (2.53%) than with semi-rigid catheters (0.79%). All malpositions but one were detected on chest X-ray. DISCUSSION: Our data suggest that the incidence of catheter malposition depends on the site of insertion, the type of material used, but not on the experience of the physician who inserted the catheter. Scrupulous use of preventive practices reduces the frequency of malpositioned catheters, but physicians must keep in mind potential pitfalls. Injection of radioopaque contrast medium into the catheter during control chest X-ray should be done even with opaque catheters.

Adult↗

Supraclavicular approach to the subclavian/innominate vein for large-bore central venous catheters.

Infraclavicular and internal jugular catheterization are commonly used techniques for hemodialysis access, but may at times be impeded in patients whose anatomy makes cannulation difficult. In an effort to enlarge the spectrum of alternative access sites, we evaluated the supraclavicular approach for large-bore catheters. During an 18-month period we prospectively collected data on success rate and major and minor complications of the supraclavicular access for conventional dialysis catheters as well as Dacron-cuffed tunneled devices in 175 adult patients admitted for various extracorporeal therapies and bone marrow transplantation. Two hundred eight large-bore catheters (99 conventional dialysis catheters, 63 semirigid tunneled Dacron-cuffed catheters, and 46 Hickman catheters) were successfully placed in 164 patients (success rate, 93.8%), 58 (33.1%) of whom had been previously catheterized. Complications included pneumothorax (one patient), arterial puncture (seven patients), and puncture of the thoracic duct (two patients) without sequelae. Postinsertional chest radiographs demonstrated impressive coaxial lie of most catheters. Catheter malpositions occurred only sporadically (1%). Difficulty of introducing the catheter via a placed sheath was rarely observed. There was no clinically significant evidence of catheter-induced venous thrombosis or stenosis. We conclude that the supraclavicular route is an easy and safe first approach for large-bore catheters, as well as a useful alternative to traditional puncture sites for precatheterized and anatomically problematic patients.

Adolescent↗

Mutation (677 C to T) in the methylenetetrahydrofolate reductase gene aggravates hyperhomocysteinemia in hemodialysis patients.

Hyperhomocysteinemia is frequent in hemodialysis patients and represents an independent risk factor for vascular disease in these patients. Elevated total homocysteine (tHcy) plasma levels can results from defective remethylation of Hcy to methionine due to decreased activity of the enzyme methylenetetrahydrofolate reductase (MTHFR). A genetic aberration in the MTHFR gene (677 C to T substitution) has been shown to result in reduced MTHFR activity. We tested the hypothesis that elevation of tHcy plasma levels in hemodialysis patients is influenced by the 677 C to T mutation of the MTHFR gene and examined the relation of the genotype with tHcy, folate and vitamin B12 plasma levels in these patients. The allelic frequency of the MTHFR mutation was evaluated in 203 patients maintained on chronic hemodialysis treatment. Total Hcy, folate, vitamin B12 levels and the MTHFR mutation were analyzed in 69 of the 203 patients and in 69 age- and sex-matched healthy control subjects. The allelic frequency of the 677 C to T transition in the MTHFR gene in hemodialysis patients was 34.7% versus 35.5% in healthy controls. Of 203 patients 26 (12.8%) were homozygous for the mutation (+/+) versus 10.2% in healthy subjects. The heterozygous (+/-) genotype was identified in 43.8% of patients versus 50.7% in controls. The mean tHcy level in hemodialysis patients was 28.7 +/- 11.0 mumol/liter versus 10.0 +/- 3.0 mumol/liter in control subjects. The mean tHcy levels were 36.4 +/- 13.4 mumol/liter in (+/+) patients and 12.2 +/- 4.5 mumol/liter in (+/+) controls, 28.7 +/- 10.8 mumol/liter in (+/-) patients and 9.9 +/- 2.7 mumol/liter in (+/-) controls and 25.4 +/- 8.5 mumol/liter in (-/-) hemodialysis patients versus 9.7 +/- 2.8 mumol/liter in (-/-) controls: There was no significant difference of folate and vitamin B12 concentrations in patients and controls with different MTHFR genotypes. Analysis of covariance including age, gender, folate concentrations, vitamin B12 levels, albumin and creatinine as covariables revealed a significant influence of the (+/+) genotype, albumin and folate status on tHcy levels in hemodialysis patients. Together, our data demonstrate that the extent of hyperhomocysteinemia in hemodialysis patients is not only the result of uremia or folate status, but is also genetically determined by the (+/+) MTHFR genotype. The presence of the 677 C to T mutation in the MTHFR gene does not appear to represent a risk factor for development of end-stage renal disease.

Adult↗

Disturbed latex immunoassays for C-reactive protein and ferritin in a renal transplant patient due to polyclonal IgM hypergammaglobulinaemia.

BACKGROUND: C-reactive protein (CRP) and ferritin serum levels represent routine laboratory parameters in the monitoring of renal failure patients. Analysis of CRP, ferritin and other serum proteins can be performed using latex-enhanced or non-latex-enhanced immunoassays. We report on a renal transplant patient with polyclonal IgM hypergammaglobulinaemia having markedly elevated serum CRP and ferritin levels (as detected by latex-enhanced immunoassays) in the absence of clinical signs of an infectious or malignant disorder. METHODS: CRP and ferritin serum levels were determined with various immunoassays with and without latex enhancement. To characterize the causative agent for the elevated CRP and ferritin values, the patient's and a control serum were fractionated by gel filtration on a Sephacryl S-300 column. Serum fractions were subjected to further analysis for reactivity in CRP and ferritin assays. In addition, patient's serum samples were investigated for reactivity with various other latex-based immunoassays (rheumatoid factor, antistreptolysin O, antistreptococcal DNase B). RESULTS: Using latex-enhanced CRP and ferritin immunoassays, markedly elevated serum levels were obtained (CRP 726 mg/l determined by turbidimetry, 398 mg/l determined by nephelometry; ferritin, 20,000 micrograms/l determined by turbidimetry). In contrast, assays without latex enhancement revealed levels within the normal range for both serum proteins (CRP < 5 mg/l, ferritin 52 micrograms/l). The analysis of the patient's serum by gel filtration revealed an interference of the patient's IgM with latex particles used in the CRP and ferritin assays. CONCLUSION: Our study demonstrates that even polyclonal IgM hypergammaglobulinaemia can disturb a large array of latex-enhanced immunoassays used for routine diagnostic procedures. This is of particular interest for the management of allograft recipients in whom monoclonal and polyclonal gammaglobulinaemia are frequently observed. We therefore recommend reanalysis of the respective plasma proteins by latex-free assays in patients with hypergammaglobinaemia showing no clinical signs of an acute infectious disease or malignant disorder.

C-Reactive Protein↗

Percutaneous nonangiographic insertion of Hickman catheters in marrow transplant recipients by anesthesiologists and intensivists.

Long-term central venous lines for chronic hemoaccess are usually inserted in the operating theater under local or general anesthesia or in interventional radiology suites using fluoroscopic technique. In a prospective study we determined the feasibility of percutaneous insertion of Hickman catheters without fluoroscopic control by anesthesiologists and intensivists in the setting of an intensive care unit. Fifty-four Hickman catheters were placed in 53 consecutive patients with hematological disorders and/or neoplastic diseases undergoing allogeneic or autologous bone marrow transplantation (BMT) or buffy coat therapy. There were no major complications. The mean time for insertion was 35 min. The median life span of catheters was 70 days (range 3-214). Twenty-six catheters were electively removed; six remained functioning in situ at the end of the study. For 3333 catheter days (1471 days in hospital and 1862 days at domiciliary care), six catheters were removed because of mechanical complications (inadvertent dislodgement, leak, secondary migration) and 14 because of suspected or documented infection. We conclude that percutaneous nonangiographic insertion of Hickman catheters by anesthesiologists minimizes technical expenditure and is at least as effective as surgical or radiological techniques. The rate of clinically important complications is acceptable.

Adolescent↗

Laboratory diagnosis of anaemia in dialysis patients: use of common laboratory tests.

Almost all patients with end-stage renal disease suffer from renal anaemia of multifactorial pathogenesis. The use of recombinant human erythropoietin to raise the haematocrit has been a major advance in the care of patients with end-stage renal disease. The majority of these patients develop absolute or functional iron deficiency. However, the diagnosis of iron deficiency is hindered by the inaccuracy of commonly used tests. Serum ferritin and transferrin saturations are frequently used, but limitations with both parameters in end-stage renal disease patients have resulted in the development of new tests to assess iron sufficiency. The percentage of hypochromic red blood cells and particularly reticulocyte haemoglobin content are new measures of iron status in end-stage renal disease patients. An enhanced knowledge of the interpretation of available laboratory parameters will ensure that the patients receive the full benefit from their treatment with recombinant human erythropoietin and iron.

Anemia↗