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Biomedical subjects

U Kuhlmann

Publications and source records attributed to U Kuhlmann.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of L-carnitine on leukocyte function and viability in hemodialysis patients: A double-blind randomized trial.

Excess morbidity and mortality among long-term hemodialysis patients because of infectious complications is partly caused by an impairment of cellular immune defense. We hypothesized this impairment is related to an abnormal carnitine metabolism also present in these patients. In a double-blind, randomized, placebo-controlled trial, we investigated the effect of L-carnitine on phagocytic function and viability of blood leukocytes in 17 patients undergoing maintenance hemodialysis. After an observation period of 1 month, the patients received either 10 mg/kg of L-carnitine or placebo intravenously at the end of each hemodialysis session over a period of 4 months. Leukocyte oxidative metabolism was measured by means of luminol-enhanced chemiluminescence and superoxide generation after stimulation with Staphylococcus aureus or phorbol myristate acetate. Killing capacity and phagocytosis of radiolabeled staphylococci were determined. A lactate dehydrogenase (LDH) release test was applied to assess cell viability. We were unable to show an effect of L-carnitine on phagocytic function and viability in vivo. Several clinical parameters were observed during the trial. No statistically significant differences concerning dialysis-related morbidity, anemia, or reduction of blood urea nitrogen and creatinine levels were detected. Additionally, we tested the effect of L-carnitine on phagocytic function after in vitro incubation of blood leukocytes, which also showed no changes. LDH release was decreased, indicating an improved viability of these cells. The latter results were found after in vitro incubation of cells, but could not be confirmed in vivo. In summary, we could not show beneficial effects of L-carnitine administration in hemodialysis patients for the dosage and duration of treatment stated, either on phagocytic function and viability or on the clinical and biochemical parameters observed.

Adult↗
PubMed1999

Pharmacokinetics of morphine and its glucuronides following intravenous administration of morphine in patients undergoing continuous ambulatory peritoneal dialysis.

BACKGROUND: Conjugation with glucuronic acid represents the major route of biotransformation of morphine. The glucuronides morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are eliminated via the kidneys. Therefore, chronic renal failure should affect the disposition of M3G and M6G. Numerous patients undergoing long-term continuous ambulatory peritoneal dialysis (CAPD) require pain treatment with morphine. There are only limited data available about the disposition of morphine and its active metabolites M6G and M3G in patients on CAPD. We therefore investigated the pharmacokinetics of morphine and its metabolites in CAPD patients. METHODS: This was a single intravenous dose pharmacokinetic study in 10 CAPD patients (1 female, 9 male, age 31-69 years). Morphine-hydrochloride (Mo) (10 mg) was administered intravenously. Serum, urine, and dialysate samples were collected during 24 h. GC-MS-MS and HPLC-MS methods were used to quantify respectively morphine and morphine glucuronides. RESULTS: While systemic clearance of morphine (1246+/-240 ml/min) was in the range observed in patients with normal kidney function, both M3G and M6G showed substantial accumulation. The area under the concentration-time curve (AUC) ratio of M3G:Mo (33.4+/-7.1) and of M6G:Mo (12.2+/-3.2) was 5.5 and 13.5 times higher than in patients with normal kidney function. Renal clearances of morphine, M3G, and M6G (morphine 3.0+/-2.5 ml/min; M3G 3.9+/-2.2 ml/min; M6G 3.6+/-2.2 ml/min) and dialysate clearances (morphine 4.1+/-1.3 ml/min; M3G 3.2+/-0.7 ml/min; M6G 3.0+/-0.8 ml/min) were extremely low. Therefore the accumulation of M6G and M3G is readily explained by kidney failure which is not compensated by CAPD. CONCLUSION: Accumulation of M3G and M6G is due to the substantially lowered clearance by residual renal function and peritoneal dialysis. In view of the accumulation of potential active metabolites, subsequent investigations have to assess the frequency of side-effects in patients on CAPD.

Adult↗
PubMed1999

On-line monitoring of the intravascular volume during haemodialysis by continuous refractometry.

The control of intravascular volume (IVV) by continuous on-line measurement of protein concentration would optimise the patients' specific rate of ultrafiltration. To prove the accuracy of a refractometric device, plasma was continuously drawn by haemofiltration during 10 haemodialysis treatments of male patients. Refractometry reflects highly significant changes in the concentrations of filtrate proteins (r = 0.862, p < 0.001) and blood proteins (rtotal = 0.593, ptotal < 0.001). In vitro, the refractometric device detected a change of protein concentration of 0.041 g/L through a refraction increase of 0.1 mV. The power of discrimination was 0.067% of IVV However, in vivo, the accuracy of IVV refractometric monitoring is reduced by interference factors such as sodium (0. 141 mV/mmol/L), glucose (0.034 mV/mg/dl) and triglycerides (-0.040 mV/mg/dl). Adjustment of the refraction data using sodium and glucose electrodes and plasma filters with a cut-off below the size of chylomicrons is recommended.

Blood Proteins↗
PubMed1999

Phthalic acid is the main metabolite of the plasticizer di(2-ethylhexyl) phthalate in peritoneal dialysis patients.

Di(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer in polyvinyl chloride (PVC) plastics, and is therefore a major constituent of continuous ambulatory peritoneal dialysis (CAPD) bags. Because DEHP is not chemically bound, it leaches out of the plastic matrix. Recently, we found that leukocyte function in vitro is impaired by a mixture of metabolites of DEHP. In the present study, we investigated the metabolism of DEHP in patients on CAPD. The study group consisted of 10 stable patients, on CAPD for at least 6 months, using a plasticizer-containing PVC PD system [ANDY Plus (Fresenius Medical Care, Bad Homburg, Germany)]. Effluent dialysate and urine samples were collected over 24 hours, and a 10 mL blood sample was drawn. Concentrations of DEHP and its metabolites mono(2-ethylhexyl) phthalate (MEHP), phthalic acid (PA), and 2-ethylhexanol (2-EH) were determined in urine, dialysate, and serum using gas chromatography/mass spectrometry. Additionally, the degree of glucuronidation of the phthalic acid esters in urine were determined. In serum, dialysate, and urine, PA was the predominant metabolite of DEHP (0.205 +/- 0.067 mg/L, 0.284 +/- 0.180 mg/L, and 1.34 +/- 1.00 mg/L, respectively), but concentrations of MEHP were low (0.0100 +/- 0.0056 mg/L, 0.022 +/- 0.008 mg/L, 0.011 +/- 0.0064 mg/L, respectively). Urinary MEHP was glucuronidated to approximately 15%. PA was 35% eliminated as a glucuronide. Unlike healthy subjects, PD patients do not eliminate DEHP mainly in the form of MEHP or MEHP metabolites. They further break these compounds down to PA. The fact that concentrations of PA in urine exceed by far the respective serum concentrations indicates that PA is secreted by the kidney. Further research on the toxicological aspects of plasticizers in uremic patients should take these findings into account.

Chromatography, Gas↗
PubMed1998

[Cervical actinomycosis in systemic lupus erythematosus, nephrocalcinosis and distal renal tubular acidosis (type I-RTA)].

HISTORY AND CLINICAL FINDINGS: A 25-year-old woman presented with a painful soft-tissue swelling in the right neck, which made it impossible to assess the right cervical lymph nodes, while other lymph nodes were unremarkable on palpation. For 9 years she had been known to have polyarthritis. All joints were freely mobile and were without deformity or inflammatory signs. Flexion of the left elbow was slightly painful but freely mobile. There was no skin rash. INVESTIGATIONS: Erythrocyte sedimentation rate was 44 mm/h, there was a leucocytosis of 16,000 granulocytes/ml. There was hypokalaemia (3.5 mEq/l) and a metabolic hyperchloremic acidosis with a pH of 7.27 and a urinary pH of 6.5. Antinuclear and anti-ds-DNA antibodies were raised (ANA: 3.9 multiple of cutoff point [MOC; normal: 0-1.0]; anti-ds-DNA antibodies: 4.0 [normal: 0-1.0])-Fine needle aspiration cytology from the swelling revealed erythrocytes, double-refractory horny lamellae, cellular debris and only a few inflammatory cells. Abdominal ultrasound showed nephrocalcinosis. Microbiological cultures were negative. DIAGNOSIS, TREATMENT AND COURSE: Assuming a bacterial cause of the swelling antibiotic treatment with Phenoxymethylpenicillin (4 MU/d) was initiated. The local findings rapidly improved and the inflammatory parameters regressed to normal. 16 weeks after the initial admission the abscess recurred and biopsy now revealed actinomycetes with typical granules, confirming cervical actinomycosis. The other symptoms indicated autoimmune disease and, together with previous findings, established the additional diagnosis of lupus erythematodes, which caused the type 1 distal tubular acidosis. CONCLUSIONS: This case illustrates the basic approach of establishing an all-encompassing diagnosis that brings together seemingly isolated findings. It is especially in systemic disease that such diagnostic strategy will frequently lead to its recognition.

Acidosis, Renal Tubular↗
PubMed1998

Severe thrombocytopenia and response to corticosteroids in a case of nephropathia epidemica.

Nine days after working in the woods, a previously healthy 32-year-old man fell seriously ill. His symptoms included high fever, chills, diffuse myalgia, severe headache, and back pain. On the fifth day of onset of symptoms, blood tests showed creatinine levels of 5.4 mg/dL accompanied by marked proteinuria. After admission to the hospital, a diagnosis of nephropathia epidemica (NE) caused by Puumala virus was made using solid-phase enzyme-linked immunosorbent assay (ELISA). The patient gradually recovered renal function without requiring dialysis. However, he surprisingly experienced a sharp decline in platelet count to a minimum of 2,000/microL with concomitant occurrence of petechiae and conjunctival hemorrhage. Prednisolone was initiated, resulting in a swift rise in platelets. Six days later, when the medication was withdrawn, a sharp decrease in platelets recurred. The steroids were then readministered for the next 3 months, thus reestablishing a stable platelet count. The immediate rise of platelets after administration of prednisolone supports the pathophysiological view of hantavirus infection as an immunologically mediated disease. Corticosteroids in the treatment of hantavirus-associated thrombocytopenia might need further systematic evaluation.

Adult↗
PubMed1997

In vitro effects of glucose polymer-containing peritoneal dialysis fluids on phagocytic activity.

Commercially available peritoneal dialysis fluids (PDFs) are known to impair peritoneal cellular defense mechanisms. We have investigated the influence of glucose polymer-containing PDFs on phagocytic function in vitro. Polymorphonuclear neutrophils (PMNLs) and monocytes (MNs) from 10 continuous ambulatory peritoneal dialysis patients and 10 healthy donors were incubated in PDFs containing either 7.5% icodextrin (glucose polymer) or 1.5% glucose at original pH and pH 7.4. Chemiluminescence response and H202 production were measured following stimulation with preopsonized Staphylococcus epidermidis or phorbol myristate acetate. Phagocytosis of radiolabeled bacteria and killing capacity of the cells were determined. A comparison of the impact of glucose polymer versus glucose-containing solutions at their original pH on the oxidative metabolism of the cells showed a highly significant difference (P < 0.0001) in favor of glucose polymers for H202 production of PMNLs (7.78 +/- 4.5 nmol cytochrome C reduction/10(6) cells/min v 1.11 +/- 0.67 nmol cytochrome C reduction/10(6) cells/min) and MNs (7.66 +/- 3.6 nmol cytochrome C reduction/10(6) cells/min v 1.29 +/- 0.86 nmol cytochrome C reduction/10(6)cells/min). Correspondingly, PMNLs and MNs incubated in glucose polymers showed a significantly higher chemiluminescence response irrespective of the stimulant used (P < 0.0001). Applying the killing assay on PMNLs also revealed a significantly higher percentage of inactivated bacteria (45.5% +/- 11.0% v 29.2% +/- 15.5%; P < 0.05). After adjustment of pH to 7.4, a significant difference could only be found for H202 production of PMNLs in favor of glucose polymers (16.73 +/- 6.98 nmol cytochrome C reduction/10(6) cells/min v 11.65 +/- 5.37 nmol cytochrome C reduction/10(6) cells/min; P < 0.05). In addition, we compared the glucose-polymer solution to an otherwise equally composed equiosmolar solution that contained 0.274% glucose instead of glucose polymers. No significant differences were detected with any of the tests applied. Our data suggest that glucose polymer solutions are comparatively less suppressive to phagocytic function than currently used glucose-containing PDFs. This effect may be attributed to the low osmolarity of these solutions.

Adult↗
PubMed1996

[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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗