L-carnitine does not alleviate uremic pruritus in hemodialysis patients.
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Antipruritics↗
Biomedical subjects
T Mettang
Publications and source records attributed to T Mettang.
Plasticizers in renal failure: aspects of metabolism and toxicity.
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Animals↗
[Sternocostoclavicular hyperostosis].
HISTORY AND CLINICAL FINDINGS: A 35-year-old previously healthy man developed a painful swelling in the area of the left sternoclavicular joint (SCJ), restricting movement. There had been no history of trauma. INVESTIGATIONS: A moderately increased erythrocyte sedimentation rate was the only abnormal finding among the usual laboratory tests. Radiologically there were marked hyperostotic changes in the area of the left upper thoracic cage with synostosis of the SCJ. Biopsy of the left clavicle showed non-specific chronic sclerosing osteomyelitis. TREATMENT AND COURSE: Over the next 6 years the SCJ became completely ankylosed and there were now extensive fibroses, some presternal and some in the upper mediastinum with thrombosis of the left subclavian, axillary and jugular veins causing inflow occlusion (Paget-von-Schroetter-syndrome). Lymph nodes in the region of the mandible, jugular veins bilaterally and mediastinum were noted for the first time, remaining unchanged in size over six months. CONCLUSION: Sternoclavicular hyperostosis is an important condition in the differential diagnosis of inflammatory or malignant processes of this joint.
Adult↗
[Uremic pruritus. Pathophysiologic and therapeutic concepts].
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Humans↗
Uraemic pruritus and exposure to di(2-ethylhexyl) phthalate (DEHP) in haemodialysis patients.
Uraemic pruritus is a frequent and disabling symptom in patients on dialysis. The pathogenesis of uraemic pruritus is nevertheless still obscure. We investigated whether di(2-ethylhexyl)phthalate (DEHP), the most commonly used plasticizer in polyvinylchloride (PVC) haemodialysis tubings, is a possible pathogenetic factor in uraemic pruritus. Serum concentrations of DEHP and its major derivatives mono-(2-ethylhexyl)phthalate (MEHP), 2-ethylhexanol (2-EH) and phthalic acid (PA) were determined in uraemic patients before and after a haemodialysis session and compared with the occurrence and intensity of pruritus in these patients. Twenty-one patients on regular haemodialysis for at least 6 months were examined. The severity of uraemic pruritus was assessed using a standard questionnaire (pruritus score). The quantitative analysis of DEHP and its derivatives was carried out by GC/selected ion monitoring mass spectrometry. Fourteen out of 21 patients (66%) complained about uraemic pruritus to a variable degree. The post-dialysis serum concentrations of DEHP, MEHP and 2-EH were significantly higher than the corresponding pre-dialysis values, whereas the post-dialysis concentrations of PA (0.122 +/- 0.078 microgram/microliter) were significantly lower than pre-dialysis levels (0.194 +/- 0.101 microgram/microliter, P = 0.00068). Neither pre- nor post-dialysis serum concentrations of DEHP, MEHP, PA or 2-EH were correlated with the severity of uraemic pruritus. Additionally, serum concentrations of DEHP and its metabolites did not differ significantly in patients with and without pruritus. These findings suggest that patients on haemodialysis are regularly exposed to considerable amounts of DEHP and metabolites. Phthalic acid, one of the presumed end products of DEHP metabolism, might be eliminated at least in part by haemodialysis. The exposition to DEHP and metabolites during haemodialysis, as assessed by measuring serum concentrations, bears no immediate relation to the occurrence or intensity of uraemic pruritus.
Adult↗
Low-dose intradermal versus intramuscular hepatitis B vaccination in patients with end-stage renal failure. A preliminary study.
Patients with end-stage renal disease (ESRD) are at high risk of hepatitis B infection. Only 50-60% of the patients respond adequately to the routinely performed intramuscular (i.m.) hepatitis B vaccination. We examined whether low dose intradermal (i.d.) application of the vaccine is equivalent to regular i.m. administration. Thirty-two patients with ESRD of different etiologies were investigated at the onset of dialysis treatment [11 patients on continuous ambulatory peritoneal dialysis (CAPD) and 21 patients on hemodialysis (HD)]. Patients were vaccinated at month 0, 1, 3 and 6 with either 40 micrograms HBs Ag (2 ml Engerix B, 14 patients) i.m. or with 10 micrograms HBsAg (0.5 ml Engerix B, 18 patients) i.d. The i.m. vaccination was applied in the deltoid muscle, while for i.d. vaccination the vaccine was injected into the skin of the deltoid region. Six weeks after the last vaccination anti-HBs titers were measured. 61% (11 patients) of the patients vaccinated i.d. and 64% (9 patients) of the patients vaccinated i.m. developed protective titers. Neither the height of the titers nor the proportion of patients responding to the vaccination differed significantly between the two vaccination schedules. No difference regarding the height of titers achieved or the rate of seroconversion could be found when CAPD and HD patients were analyzed separately. Only minor side effects have been observed. According to these preliminary data i.d. hepatitis B vaccination in patients with ESRD may be equivalent to i.m. administration of the vaccine. Given equivalency i.d. vaccination may be a cost-saving alternative to i.m. vaccination (only a quarter of the dose of i.m. administered vaccine is needed) with a good practicability (vaccination can be performed during HD) and a low rate of side effects.
Female↗
In vitro effects of bicarbonate- versus lactate-buffered continuous ambulatory peritoneal dialysis fluids on peritoneal macrophage function.
At present, lactate is the most commonly used buffer in peritoneal dialysis fluids (PDFs). The high lactate concentration in combination with low original pH was demonstrated to suppress phagocytic function. We evaluated the in vitro effects of a newly formulated bicarbonate-buffered PDF containing glycylglycine (BiGG15 and BiGG40; Pierre Fabre Medicament, Castres, France) on peritoneal macrophage (PMO) function, and compared them with those of equiosmolar lactate-buffered PDF (1.5% and 4.25% glucose; pH 5.4 and pH 7.4) and control buffer. Peritoneal macrophages were isolated from the effluents of 10 continuous ambulatory peritoneal dialysis patients and tested for luminol- and lucigenin-enhanced chemiluminescence, superoxide (O2-) generation measured by cytochrome c reduction, killing capacity, and phagocytosis after incubation in the PDF used. Exposure of PMO to lactate-buffered PDF with an original pH of 5.4 resulted in a significant suppression of all PMO functions measured, compared with bicarbonate- and lactate-buffered PDFs with a pH of 7.4. At physiological pH (7.4), chemiluminescence generation of PMO exposed to BiGG15/40 was significantly higher compared with the corresponding equiosmolar lactate-buffered PDF (1,992 +/- 858 x 10(3) cpm/10(4) cells v 856 +/- 398 x 10(3) cpm/10(4) cells; P < 0.004). O2- generation, killing capacity, and phagocytosis were not significantly different after PMO exposure to bicarbonate compared with exposure to lactate-buffered PDF with a neutral pH. Irrespective of the buffer used, high-osmolality PDFs suppressed PMO function significantly more than low-osmolar PDFs. In conclusion, bicarbonate-buffered PDFs are less detrimental to PMO function than lactate-containing PDFs; these preliminary in vitro results need to be confirmed in vivo.
Bicarbonates↗
In vitro effects of low-calcium peritoneal dialysis solutions on peritoneal macrophage functions.
The use of low-calcium peritoneal dialysis solutions (PDS) for continuous ambulatory peritoneal dialysis is becoming widely accepted to reduce the risk of serum hypercalcemia in patients taking calcium salts as phosphate binders. We compared the in vitro effects of low-calcium PDS (1,000 mumol calcium/L), calcium-free buffer, and buffers with increasing calcium concentrations (500 to 5,000 mumol calcium/L) on peritoneal macrophage (PMO) functions. Peritoneal macrophages isolated from 10 continuous ambulatory peritoneal dialysis patients were incubated in the different solutions and tested for phagocytic and killing capacity, superoxide generation (cytochrome-C reduction and lucigenin-enhanced chemiluminescence), and the rate of myeloperoxidase-dependent oxidative metabolism (luminol-enhanced chemiluminescence). All functions of the PMO incubated in calcium-free buffer were significantly suppressed compared with the PMO incubated in calcium buffers. No dose-dependent increase of a single PMO function could be found after incubating the PMO in calcium buffer with increasing concentrations. Incubation of PMO in otherwise identical PDS containing 1,000, 1,450, or 1,750 mumol calcium/L did not result in significantly different PMO functions. Acidic PDS (pH 5.3 to 5.5) suppressed all measured PMO functions as compared with their neutralized counterparts (pH 7.4), irrespective of the calcium concentration. Results of our in vitro study show that low-calcium PDS does not suppress PMO functions any more than standard-calcium PDS (1,750 mumol calcium/L) does.
Acridines↗
Propafenone in a usual dose produces severe side-effects: the impact of genetically determined metabolic status on drug therapy.
We report the case of an elderly lady presenting with dizziness, a head injury resulting from a fall and bradycardia. Propafenone 150 mg t.i.d. had been prescribed for atrial fibrillation with tachyarrhythmia, induced by hyperthyroidism, 18 months earlier. A toxic concentration of parent propafenone, and no 5-hydroxy metabolite, was detected in a plasma sample. Symptoms disappeared after the discontinuation of propafenone. The poor metaboliser (PM) phenotype of sparteine/debrisoquine was assumed and subsequently confirmed by phenotyping (sparteine test) and genotyping (allele-specific polymerase chain reaction). The PM phenotype is common in European populations, with a prevalence of about 7%. If drugs with narrow therapeutic ranges undergo genetically polymorphic metabolism, toxicity may arise even with recommended doses. Individualization of doses is required to avoid adverse effects.
Aged↗
In vitro effects of amino-acid-based versus glucose-based continuous ambulatory peritoneal dialysis fluids on peritoneal macrophage function.
We studied the in vitro effects of peritoneal dialysis fluids (PDF) containing 1 and 1.5% amino acids (AA) as compared to approximately equiosmolar glucose (GLU)-based PDF (1.5 and 4.25%) and control buffer, respectively, on peritoneal macrophage (PMO) function. The media were tested at original pH (5.3-5.5) and after pH adjustment to 7.4. PMO were isolated from the effluents of 10 on continuous ambulatory peritoneal dialysis (CAPD) patients and tested for luminol- and lucigenin-enhanced chemiluminescence (CL), superoxide generation measured by cytochrome c reduction, killing capacity and phagocytosis after incubation (30 min, 37 degrees C) in the PDF used. All AA-based PDF exhibited a statistically significant depressive effect on integral CL response, O2- production and bacterial killing of PMO at pH 7.4 in comparison with pH-adjusted GLU-based PDF of similar osmolality and buffer. Exposure of PMO to acidic AA-based media did not result in a significantly different suppression of the oxidative metabolism and the killing capacity as compared to fresh GLU-based fluids. Phagocytosis of PMO did not show significant differences after incubation in the solutions studied. Thus, the AA-based PDF employed compromise the oxidative metabolism and the killing capacity of PMO at pH 7.4 in vitro significantly more than GLU-based fluids. Since pH-identical and almost equiosmolar PDF were compared, the specific composition of the AA-based fluids, especially the high content of lactate and several essential AA, could be responsible for this detrimental impact.
Amino Acids↗
[Lethal Salmonella enteritidis meningoencephalitis in an adult with a carcinoma of an unknown primary site].
A 71-year-old man with an aortobifemoral bypass graft had experienced several episodes of severe pain in the thoracic and lumbar spine, followed by severe abdominal pain, during the preceding two weeks. Physical examination, chest X-ray, ultrasonography and computed tomography of the abdomen provided no specific pointers to a diagnosis. He was anaemic (haemoglobin 95 g/l), but had a normal WBC count with neutrophilia (up to 91%) and thrombocytopenia (up to 24,000/microliters). The transaminase and lactate dehydrogenase activities were raised, as were the bilirubin level and the retention values. There was a metabolic acidosis (pH 7.20). Because of suspected septicaemia ciprofloxacin (twice daily 200 mg) was administered intravenously. But the patient gradually lost consciousness, required mechanical ventilation and died 24 hours after admission in circulatory failure. Autopsy revealed a meningoencephalitis, carcinoma of unknown primary with bone marrow carcinomatosis as well as widespread carcinomatosis of blood and lymph vessels. The findings of blood, urine and sputum cultures, available only postmortally, revealed growth of tetracycline-resistant Salmonellae enteritidis.
Aged↗
Epidermal Langerhans cells in uremic patients on hemodialysis or continuous ambulatory peritoneal dialysis.
Skin biopsies of 33 uremic patients-13 patients on continuous ambulatory peritoneal dialysis (CAPD), 12 on hemodialysis (HD), 8 patients with end-stage renal disease (ESRD) before initiation of dialysis treatment-and 10 healthy volunteers were investigated to determine the number of Langerhans cells (LC) by light microscopy after staining for S-100 protein. The epidermal LC count was significantly lower in patients on CAPD (mean: 62.9 LC/mm2; p = 0.027) and patients on HD (mean: 30.4 LC/mm2; p = 0.0015) compared to controls (mean: 110.1 LC/mm2) and uremic patients before initiation of dialysis treatment (mean: 122.6 LC/mm2). The difference between LC counts of CAPD and HD patients did not reach statistical significance (p = 0.057). There was no relation between LC count and age (p = 0.057) or epidermal width (p = 0.26). No statistically significant correlation could be demonstrated between duration of dialysis and LC count (r = -0.33, p = 0.10). LC counts of CAPD patients with diabetes mellitus (n = 7) were not significantly different from those of nondiabetics (n = 6; p = 0.77). LC counts seem to be normal in uremic patients before dialysis treatment. The reduction in LC density in the skin of dialysis patients may contribute to immunodeficiency of uremic patients on regular dialysis treatment.
Adult↗
Intradermal hepatitis B vaccination in nonresponsive hemodialysis patients.
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Aged↗
Survival of 138 surgically placed straight double-cuff Tenckhoff catheters in patients on continuous ambulatory peritoneal dialysis.
OBJECTIVE: To determine the natural history of a surgically placed Tenckhoff catheter in patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Prospective 7-year study analyzing catheter survival of all catheters using the Kaplan-Meier life table methodology. SETTING: Teaching hospital, department of nephrology. PATIENTS: One hundred and fifteen unselected patients beginning CAPD. INTERVENTIONS: Removal of the catheter required for the following complications: exit-site or tunnel infections or relapsing peritonitis, outflow obstruction, pericatheter leak, and development of hernias. MAIN OUTCOME MEASURES: Period between insertion and removal of the catheter. RESULTS: The cumulative survival of all catheters after 1, 2, and 3 years of CAPD was 87%, 69% and 65%. Catheter survival of the first versus the second catheter after 1 year was significantly longer (p = 0.03). The difference was not significant in relation to diabetes, age, and sex. Infectious complications caused 61% (n = 19) of all 31 catheter failures, mainly due to tunnel infections caused by Staphylococcus aureus (n = 12). "Mechanical" complications accounted for 49% (n = 12) of catheter failures. Eight of 12 mechanical complications were outflow failures. Seven patients had to be transferred to hemodialysis. CONCLUSIONS: The straight Tenckhoff catheter is a reliable peritoneal access device for CAPD in an unselected patient population.
Catheters, Indwelling↗
[Acute kidney failure caused by hantavirus infection].
A 37-year-old man suddenly fell ill with high fever (up to 39.6 degrees C), headache and lumbar pain. There was marked thrombocytopenia (minimal level of 48,000/microliters), moderate anaemia and a slow rise in serum lipase concentration to maximally 1352 U/l. Marked sinus bradycardia (to as low as 34 beats/min) occurred in the further course of the disease, as well as upper abdominal pain (endoscopically diagnosed as antral gastritis), subileus and splenomegaly. Two haemodialysis treatments were needed because of acute renal failure. An IgG antibody titre of 1:512 and an IgM titre of 1:80 against hantavirus antigen confirmed that this virus was responsible for the haemorrhagic fever with renal syndrome. This infection, transmitted by wild rodents and frequently observed in Asian countries, has a rising incidence in Central Europe. It should be included in the differential diagnosis of acute renal failure of uncertain cause.
Acute Disease↗
[Continuous ambulatory peritoneal dialysis. Patient and method survival rate, peritonitis incidence and dialysis efficacy over 10 years].
From 1979 to 1989, continuous ambulatory peritoneal dialysis (CAPD) was undertaken for terminal renal failure in 104 patients (56 women and 48 men; average age 54 +/- 15.3 years at the onset of dialysis), for a total observation period of 175 patients years. Survival rate for patients and methods and dialysis effectiveness were analysed retrospectively, the incidence of peritonitis prospectively, 40 patients were aged 60 years and over. Diabetic nephropathy was the most common cause of terminal renal failure (44%). Cumulative patient survival rate was 80% in the first year of treatment; 57% of patients were still alive after two years. The cause of death in 45 of the 54 patients who had died was unrelated to CAPD, cardiac disease and cerebrovascular accident being the most frequent causes (n = 26). During the first treatment year 47% of patients contracted bacterial peritonitis, 59% during the first two years. In 9% of patients CAPD had to be discontinued within the first two treatment years because of CAPD-related complications. There was no case of sclerosing peritonitis or of ultrafiltration loss forcing CAPD termination. These data indicate that there is no plausible explanation from a medical viewpoint for the highly restrictive use of CAPD in the Federal Republic of Germany.
Combined Modality Therapy↗
In vivo effect of 1,25-dihydroxyvitamin D3 on phagocyte function in hemodialysis patients.
1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has been shown to modulate the immune function of monocytes and macrophages. Patients with end-stage renal disease (ESRD) on chronic hemodialysis treatment usually present a deficiency of this active form of vitamin D3. The aim of this study was to investigate the effect of 1,25(OH)2D3 replacement therapy on phagocytosis, bactericidal capacity, and oxidative metabolism of peripheral blood polymorphonuclear leukocytes (PMNL) and monocytes (MN) in chronic hemodialysis patients. Phagocyte function tests were performed before and after four weeks of an oral replacement therapy with 0.5 micrograms/day of 1,25(OH)2D3 (Rocaltrol). The superoxide (O2-) generation of monocytes, measured by cytochrome c reduction and lucigenin-enhanced chemiluminescence (CL) from patients receiving hemodialysis treatment was significantly diminished compared to healthy controls. After the replacement therapy with 1,25(OH)2D3 the O2- production showed a significant improvement, resulting in an increased cytochrome c reduction and lucigenin-CL response. The bactericidal capacity of MN was also impaired and exhibited a significant enhancement of their killing activity after the administration of 1,25(OH)2D3. On the other hand, the luminol-enhanced CL, which reflects the myeloperoxidase-dependent oxidative metabolism, and the phagocytic ability of MN was not affected by the hormone. The function of polymorphonuclear leukocytes (PMNL) from hemodialysis patients showed no impairment in the state of 1,25(OH)2D3 deficiency and the replacement of the hormone did not enhance their function. These results suggest that the deficiency of 1,25(OH)2D3 in patients with ESRD on chronic hemodialysis treatment may be responsible for an impaired monocyte function, which could be improved by an in vivo replacement of the hormone.
Adult↗
Measurement of 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid and its metabolite 12-oxo-5Z,8E,10E-heptadecatrienoic acid in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry.
Thromboxane A2, the predominant product of arachidonic acid metabolism in the blood platelet, is a potent vasoconstrictor and platelet agonist. During its biosynthesis from cyclic endoperoxide, 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) is formed in equal amounts. The further metabolism of HHT, catalyzed by 15-hydroxyprostaglandin dehydrogenase, leads to 12-oxo-5Z,8E,10E-heptadecatrienoic acid (Oxo-HT). Sample workup procedures are described which allow for the sensitive and reproducible determination of these two arachidonic acid metabolites in human plasma by gas chromatography-mass spectrometry in the presence of deuterated analogues as internal standards. HHT is derivatized to the pentafluorobenzyl ester tert-butyldimethylsilyl ether. In order to enable quantification of low concentrations of about 10 pg/ml in nonstimulated human plasma, the samples have to be purified by HPLC. Oxo-HT is derivatized to the pentafluorobenzyl ester, which is purified by HPLC, and then derivatized to the trimethylsilyloxime. The method allows quantification of Oxo-HT in concentrations down to 10 pg/ml plasma. The reported methods have been used to measure HHT and Oxo-HT in stimulated platelet rich plasma and to quantify HHT in nonstimulated plasma. Determination of endogenous levels of these two arachidonic acid metabolites may give new insights into the overall biosynthesis of thromboxane A2 in man.
Blood Platelets↗