Whereas nonsteroidal antiinflammatory drugs may give rise to a haemolytic crisis in glucose-6-pho... more Whereas nonsteroidal antiinflammatory drugs may give rise to a haemolytic crisis in glucose-6-phosphate dehydrogenase (G-6PD) deficiency, administration of acetaminophen is regarded as innocuous (2, 5). In a 30 year old patient the diagnosis of an "Aachen" variant G-6-PD deficiency (3) had been made in the first year of life. After a few haemolytic crises in childhood, no acute haemotysis had occurred in past years. The last blood transfusion had been necessary 10 years ago. Arthralgias, general feeling of illness and fever (38.5°C) led to the rectal administration of 2 x 500 mg acetaminophen. In the following 48 hours an increasing haemoglobinuria developed and the patient collapsed repeatedly. On admission, jaundice, hypotension (70/40 mmHg), norrnochromic anaemia with haemoglobin 54 g/l, haptoglobin 0.1 g/l, lactate dehydrogenase 800 U/1 and unconjugated serum bilirubin 85 gmol/1 were shown. After the transfusion of 5 er3~hrocyte concentrates and a moderately forced diuresis to prevent acute renal failure, the haemolysis ceased and the patient was discharged. There was no indication of food intolerance or administration of other drugs as a cause of the haemolytic crisis. An infection induced haemolytic crisis cannot ultimately be ruled out, though an influenzal infection had never previously led to haemolysis. Bartsocas (1) has also reported a direct chronological correlation between acetaminophen (500 rag) and a haemolytic crisis in G-6-PD deficiency. Pootrakul (4) has shown that 1000 mg acetaminophen daily for 6 days led to haemolysis, measured by erythrocyte half-life in hemizygotes for a G-6-PD deficiency. Therefore, acetaminophen in G-6-PD deficiency cannot be regarded as innocuous, since it may induce a haemolytic crisis in these patients.
The aim of the present study was to investigate the pharmacokinetics of tilidine and its metaboli... more The aim of the present study was to investigate the pharmacokinetics of tilidine and its metabolites during the dialysis procedure and in the dialysis-free interval. Tilidine is a prodrug that is metabolized presystemically into the active metabolite nortilidine. Nortilidine is degraded thereafter to bisnortilidine and several polar metabolites. Nine patients with a creatinine clearance < 5 ml/min were treated in a crossover design with single oral doses of 1.5 mg/kg on the day of dialysis (dialysis performed from 3 to 6 hours after drug administration) and on a day in the dialysis-free interval. Blood samples were taken frequently and analyzed for tilidine, nortilidine, and bisnortilidine. Drug and metabolite concentrations were also measured in aliquots of dialysate collected during dialysis. Only negligible amounts of tilidine, nortilidine, and bisnortilidine (about 0.9% of the dose) were recovered from the dialysate. The pharmacokinetics of nortilidine and its inactive metabolite bisnortilidine was not affected by dialysis. The presystemic apparent clearance of the prodrug tilidine was decreased significantly during the dialysis-free interval. A significant decrease of the rate of elimination and an increase of the AUC of bisnortilidine were observed if these parameters were compared with data obtained from healthy volunteers. The plasma concentrations of nortilidine were comparable in patients and normal volunteers. Thus, a reduction of the dose of tilidine in patients with severely impaired kidney function seems not to be required. Tilidine and its metabolites cannot be removed from the body by dialysis.
Thirteen patients with chronic congestive heart failure of NYHA class II-III received multiple do... more Thirteen patients with chronic congestive heart failure of NYHA class II-III received multiple doses (14 days) of ramipril (5 mg once daily); the concentrations of ramipril and ramiprilat in plasma, as well as ramipril, ramiprilat, glucuronides, diketopiperazine, and diketopiperazine acid in urine were measured at various times for 14 days. One patient dropped out after the first day due to hypotension and another who accidentally received another ACE inhibitor additionally was excluded, so that 11 patients completed the study. Ramipril and ramiprilat in plasma were determined by radioimmunoassay, and ramipril and its metabolites in urine were measured by gas chromatography in the laboratories of Hoechst AG. Peak concentrations of the active substance ramiprilat were reached after about 4 h and amounted to 22.3 +/- 11.1 ng/ml after the first dose, and a peak concentration of 26.6 +/- 10.0 ng/ml was observed 2.5 +/- 1.4 h on average after administration on day 14. Practically no accumulation was observed for ramiprilat; the AUD (0-24 h) values increased from 191.3 +/- 83.1 ng.h/ml for the first study day to 238.3 +/- 98.0 ng.h/ml for day 14. As expected, only very small fractions of the dose were excreted with urine as unchanged ramipril and ramipril glucuronide. Ramiprilat is excreted with urine to a larger extent than is rampiril--on average 6.6 +/- 3.0% on the first day and 12.2 +/- 3.8% on day 14. The total amount excreted increased by 34% on average, and was mainly due to an increased ramiprilat excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was designed to evaluate the effects of the beta 1-selective adrenoceptor antagonist b... more This study was designed to evaluate the effects of the beta 1-selective adrenoceptor antagonist bisoprolol on blood pressure, heart rate, plasma catecholamines, platelet aggregation, and alpha 2- and beta-adrenoceptor density in 45 male hypertensive patients (WHO stages I-II). Following a two-week placebo phase, the patients received either 5, 10, or 20 mg bisoprolol in a double-blind randomized fashion, once daily for 12 weeks. On days - 14, 0, 1, 7, 28, 56, 84, and 1 and 2 weeks after discontinuation of treatment (administration of placebo), blood pressure and heart rate were measured in the supine and sitting position, as well as during and after a 15-min exercise period on a bicycle ergometer. Simultaneously with the hemodynamic measurements, blood samples were obtained for the determination of plasma catecholamines. Blood samples for the assessment of beta-receptor density on lymphocytes and alpha 2-receptor density on thrombocytes, as well as thrombocyte aggregation sensitivity, were collected before bicycle ergometry. Five, 10, and 20 mg bisoprolol caused dose-dependent reductions of blood pressure and heart rate at rest and at peak exercise. The responder rates (diastolic BP less than or equal to 90 mm Hg) were 33%, 67%, and 100% with 5, 10, and 20 mg bisoprolol, respectively. After discontinuation of active treatment, blood pressure and heart rate gradually returned to pretreatment values within 1-2 weeks. Plasma epinephrine and norepinephrine levels in patients in the supine position remained unchanged during the whole course of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Several effects of hemodialysis, including hemoconcentration, alterations of hemostasis or hemorh... more Several effects of hemodialysis, including hemoconcentration, alterations of hemostasis or hemorheology and endothelial activation, could potentially interfere with cerebral blood flow (CBF) regulation. These treatment-specific changes may also be crucial for the enhanced incidence of stroke in uremic patients. Nevertheless, the influence of hemodialysis on CBF has not been yet adequately studied. We registered mean blood flow velocity (MFV) in the middle cerebral artery (MCA) during hemodialysis treatment in order to evaluate its contribution on CBF changes. Transcranial Doppler ultrasonography (TCD) of the MCA was performed continuously during hemodialysis treatment in 18 stable patients (10 males and 8 females, mean age 62 +/- 11 years) with end-stage renal disease of various origin. Blood pressure (mmHg), heart rate (/min), ultrafiltration volume (ml), BV changes (deltaBV by hemoglobinometry, %), arterial blood gases (pO2, blood oxygen content, pCO2), hemostasis activation (thrombin-antithrombin III complex, ELISA) and fibrinogen (Clauss) were measured simultaneously at the beginning of treatment and every hour thereafter. Before the hemodialysis session the MFV in the MCA was within normal range (57.5 +/- 13.0 cm/s, ref. 60 +/- 12) and was mainly dependent on the patients' age (r = -0.697, p < 0.01). The blood flow velocity in the MCA decreased significantly from 57.5 +/- 13.0 cm/s before the beginning to 48.3 +/- 11.1 cm/s after four hours (n = 18, p < 0.05) and to 43.9 +/- 8.9 cm/s after five hours (n = 9, p < 0.05) of hemodialysis treatment. During hemodialysis treatment, the percentual changes of MFV in the MCA (delta%MFV) were interrelated to the ultrafiltration volume (r = -0.486, p < 0.01), the blood volume (BV%, r = 0.369, p < 0.01) and the percentual changes of the hematocrit (r = -0.358, p < 0.01), of the arterial blood oxygen content (delta%acO2, r = -0.420, p < 0.01) and of the plasma fibrinogen levels (delta%fibrinogen, r = 0.244, p < 0.05). A significant continuous decrease of the MFV in the MCA was observed during hemodialysis treatment, which inversely correlated both with ultrafiltration volume, BV changes and changes of plasma fibrinogen. The ultrafiltration-induced hemoconcentration with concomitant rise of hematocrit and oxygen transport capacity, may partly explain the alterations in the cerebral MFV observed during hemodialysis.
In a 30-year-old male patient systemic lupus erythematosus was diagnosed based on the presence of... more In a 30-year-old male patient systemic lupus erythematosus was diagnosed based on the presence of 8 out of 11 ARA criteria. Disease onset was acute and included renal function impairment with biopsy-proven lupus nephritis (WHO class IV) requiring renal replacement therapy. Although conventional immunosuppressive therapy regimens proved effective in controlling disease activity, all of the administered drugs were accompanied by serious side effects: bilateral femur head necrosis with corticosteroids, allergic skin reaction in response to azathioprine, nephrotoxicity with cyclosporine, nausea and abdominal pain with mycophenolate mofetil and life-threatening septicemia with cyclophosphamide treatment. In search for alternative treatment options, tacrolimus (FK506, trough serum levels 3-6 ng/ml) was started. FK506 was well-tolerated and lupus activity completely resolved within 7 months after initiation of therapy. During 36 months of follow-up no arthritic complaints occurred and renal function stabilized at a serum creatinine of 2.1 mg/dl with negative anti-ds-DNA antibodies and ANA titers. In conclusion, FK506 may be considered as alternative immunosuppressive for maintenance treatment in patients with severe lupus erythematosus and side effects to conventional regimens.
Summary Correlation between postthrombotic syndrome, ADP-induced aggregation and intracellular ca... more Summary Correlation between postthrombotic syndrome, ADP-induced aggregation and intracellular calcium concentration. This study presents a comparison of the ADP-induced platelet aggregation and free cytosolic platelet calcium concentration between patients with postthrombotic syndrome and healthy volunteers. The half maximal effective dose of the platelet aggregation induced by ADP was significantly decreased in postthrombotic syndrome (p<0.005). The mean values were 0.42 µmol/l
Abstract 1 This study was designed to follow changes in plasma catecholamine concentrations durin... more Abstract 1 This study was designed to follow changes in plasma catecholamine concentrations during β-adrenoceptor blockade using doses of antagonists which decreased the mean arterial pressure (MAP) by about 15 mm Hg. Noradrenaline, adrenaline and dopamine were radioenzymatically determined in 34 patients with moderate essential hypertension during an 8 week course of treatment with either pindolol (with intrinsic sympathomimetic activity, ISA) or propranolol (without ISA). Plasma catecholamines were determined before and 1, 7, 28 and 56 days after commencement of treatment and 1 week after discontinuation of treatment. 2 After one day of pindolol therapy plasma catecholamine concentrations were decreased, but no decrease in MAP was observed. After one day of propranolol therapy, however, MAP was decreased, but except for increased levels of adrenaline, plasma catecholamines showed no changes. 3 On the 56th day of therapy both β-adrenoceptor blockers had decreased the MAP. Pindolol therapy had caused a decrease in all three catecholamines whereas propranolol had caused no change except for decreased dopamine levels. 4 One week after cessation of propranolol therapy catecholamines were decreased but the MAP had begun to return to initial values; after cessation of pindolol therapy however, the MAP remained decreased. 5 The dissimilar relationships between blood pressure and catecholamine concentration during pindolol and propranolol therapy are evidence for multiple and different modes of action for β-adrenoceptor blockers with and without ISA. This study demonstrates that catecholamine concentrations were generally decreased during low-dose β-adrenoceptor blocker therapy, with lower catecholamine levels during pindolol treatment than during propranolol treatment.
Acute hepatic failure develops as a disease entity of rather diverse origin. With disease progres... more Acute hepatic failure develops as a disease entity of rather diverse origin. With disease progression, toxic bilirubin levels may cause severe complications which include AV-nodal blockage, cardiac arrhythmia, impaired consciousness, generalized seizures, and status epilepticus. Treatment choices to prevent clinical deterioration comprise of costly and limited available orthotopic liver transplantation, utilization of extracorporeal bioartificial liver support devices and haemoperfusion/plasmaperfusion treatment with activated charcoal/anion exchange filters. Here, we present a patient with acute drug-induced cholestatic hepatitis. Excessively elevated bilirubin levels were accompanied by cardiac and cerebral complications. Extracorporeal resin perfusion treatment (Plasorba, BR-350) was successfully performed over a 50-day period without activation of the coagulation system or side effects. Bilirubin levels were lowered to a minimum of 225 micromol/l, with concurrent clinical improvement. In conclusion, extracorporeal anion exchange plasmaperfusion may be a viable long-term treatment for hyperbilirubinaemic side effects in overt cholestatic hepatitis.
Heparan sulfate proteoglycans are major components of the glomerular basement membrane and play a... more Heparan sulfate proteoglycans are major components of the glomerular basement membrane and play a key role in the molecular organization and function of the basement membrane. Moreover, their presence is essential for maintenance of the selective permeability of the ...
Whereas nonsteroidal antiinflammatory drugs may give rise to a haemolytic crisis in glucose-6-pho... more Whereas nonsteroidal antiinflammatory drugs may give rise to a haemolytic crisis in glucose-6-phosphate dehydrogenase (G-6PD) deficiency, administration of acetaminophen is regarded as innocuous (2, 5). In a 30 year old patient the diagnosis of an "Aachen" variant G-6-PD deficiency (3) had been made in the first year of life. After a few haemolytic crises in childhood, no acute haemotysis had occurred in past years. The last blood transfusion had been necessary 10 years ago. Arthralgias, general feeling of illness and fever (38.5°C) led to the rectal administration of 2 x 500 mg acetaminophen. In the following 48 hours an increasing haemoglobinuria developed and the patient collapsed repeatedly. On admission, jaundice, hypotension (70/40 mmHg), norrnochromic anaemia with haemoglobin 54 g/l, haptoglobin 0.1 g/l, lactate dehydrogenase 800 U/1 and unconjugated serum bilirubin 85 gmol/1 were shown. After the transfusion of 5 er3~hrocyte concentrates and a moderately forced diuresis to prevent acute renal failure, the haemolysis ceased and the patient was discharged. There was no indication of food intolerance or administration of other drugs as a cause of the haemolytic crisis. An infection induced haemolytic crisis cannot ultimately be ruled out, though an influenzal infection had never previously led to haemolysis. Bartsocas (1) has also reported a direct chronological correlation between acetaminophen (500 rag) and a haemolytic crisis in G-6-PD deficiency. Pootrakul (4) has shown that 1000 mg acetaminophen daily for 6 days led to haemolysis, measured by erythrocyte half-life in hemizygotes for a G-6-PD deficiency. Therefore, acetaminophen in G-6-PD deficiency cannot be regarded as innocuous, since it may induce a haemolytic crisis in these patients.
The aim of the present study was to investigate the pharmacokinetics of tilidine and its metaboli... more The aim of the present study was to investigate the pharmacokinetics of tilidine and its metabolites during the dialysis procedure and in the dialysis-free interval. Tilidine is a prodrug that is metabolized presystemically into the active metabolite nortilidine. Nortilidine is degraded thereafter to bisnortilidine and several polar metabolites. Nine patients with a creatinine clearance &lt; 5 ml/min were treated in a crossover design with single oral doses of 1.5 mg/kg on the day of dialysis (dialysis performed from 3 to 6 hours after drug administration) and on a day in the dialysis-free interval. Blood samples were taken frequently and analyzed for tilidine, nortilidine, and bisnortilidine. Drug and metabolite concentrations were also measured in aliquots of dialysate collected during dialysis. Only negligible amounts of tilidine, nortilidine, and bisnortilidine (about 0.9% of the dose) were recovered from the dialysate. The pharmacokinetics of nortilidine and its inactive metabolite bisnortilidine was not affected by dialysis. The presystemic apparent clearance of the prodrug tilidine was decreased significantly during the dialysis-free interval. A significant decrease of the rate of elimination and an increase of the AUC of bisnortilidine were observed if these parameters were compared with data obtained from healthy volunteers. The plasma concentrations of nortilidine were comparable in patients and normal volunteers. Thus, a reduction of the dose of tilidine in patients with severely impaired kidney function seems not to be required. Tilidine and its metabolites cannot be removed from the body by dialysis.
Thirteen patients with chronic congestive heart failure of NYHA class II-III received multiple do... more Thirteen patients with chronic congestive heart failure of NYHA class II-III received multiple doses (14 days) of ramipril (5 mg once daily); the concentrations of ramipril and ramiprilat in plasma, as well as ramipril, ramiprilat, glucuronides, diketopiperazine, and diketopiperazine acid in urine were measured at various times for 14 days. One patient dropped out after the first day due to hypotension and another who accidentally received another ACE inhibitor additionally was excluded, so that 11 patients completed the study. Ramipril and ramiprilat in plasma were determined by radioimmunoassay, and ramipril and its metabolites in urine were measured by gas chromatography in the laboratories of Hoechst AG. Peak concentrations of the active substance ramiprilat were reached after about 4 h and amounted to 22.3 +/- 11.1 ng/ml after the first dose, and a peak concentration of 26.6 +/- 10.0 ng/ml was observed 2.5 +/- 1.4 h on average after administration on day 14. Practically no accumulation was observed for ramiprilat; the AUD (0-24 h) values increased from 191.3 +/- 83.1 ng.h/ml for the first study day to 238.3 +/- 98.0 ng.h/ml for day 14. As expected, only very small fractions of the dose were excreted with urine as unchanged ramipril and ramipril glucuronide. Ramiprilat is excreted with urine to a larger extent than is rampiril--on average 6.6 +/- 3.0% on the first day and 12.2 +/- 3.8% on day 14. The total amount excreted increased by 34% on average, and was mainly due to an increased ramiprilat excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was designed to evaluate the effects of the beta 1-selective adrenoceptor antagonist b... more This study was designed to evaluate the effects of the beta 1-selective adrenoceptor antagonist bisoprolol on blood pressure, heart rate, plasma catecholamines, platelet aggregation, and alpha 2- and beta-adrenoceptor density in 45 male hypertensive patients (WHO stages I-II). Following a two-week placebo phase, the patients received either 5, 10, or 20 mg bisoprolol in a double-blind randomized fashion, once daily for 12 weeks. On days - 14, 0, 1, 7, 28, 56, 84, and 1 and 2 weeks after discontinuation of treatment (administration of placebo), blood pressure and heart rate were measured in the supine and sitting position, as well as during and after a 15-min exercise period on a bicycle ergometer. Simultaneously with the hemodynamic measurements, blood samples were obtained for the determination of plasma catecholamines. Blood samples for the assessment of beta-receptor density on lymphocytes and alpha 2-receptor density on thrombocytes, as well as thrombocyte aggregation sensitivity, were collected before bicycle ergometry. Five, 10, and 20 mg bisoprolol caused dose-dependent reductions of blood pressure and heart rate at rest and at peak exercise. The responder rates (diastolic BP less than or equal to 90 mm Hg) were 33%, 67%, and 100% with 5, 10, and 20 mg bisoprolol, respectively. After discontinuation of active treatment, blood pressure and heart rate gradually returned to pretreatment values within 1-2 weeks. Plasma epinephrine and norepinephrine levels in patients in the supine position remained unchanged during the whole course of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Several effects of hemodialysis, including hemoconcentration, alterations of hemostasis or hemorh... more Several effects of hemodialysis, including hemoconcentration, alterations of hemostasis or hemorheology and endothelial activation, could potentially interfere with cerebral blood flow (CBF) regulation. These treatment-specific changes may also be crucial for the enhanced incidence of stroke in uremic patients. Nevertheless, the influence of hemodialysis on CBF has not been yet adequately studied. We registered mean blood flow velocity (MFV) in the middle cerebral artery (MCA) during hemodialysis treatment in order to evaluate its contribution on CBF changes. Transcranial Doppler ultrasonography (TCD) of the MCA was performed continuously during hemodialysis treatment in 18 stable patients (10 males and 8 females, mean age 62 +/- 11 years) with end-stage renal disease of various origin. Blood pressure (mmHg), heart rate (/min), ultrafiltration volume (ml), BV changes (deltaBV by hemoglobinometry, %), arterial blood gases (pO2, blood oxygen content, pCO2), hemostasis activation (thrombin-antithrombin III complex, ELISA) and fibrinogen (Clauss) were measured simultaneously at the beginning of treatment and every hour thereafter. Before the hemodialysis session the MFV in the MCA was within normal range (57.5 +/- 13.0 cm/s, ref. 60 +/- 12) and was mainly dependent on the patients&amp;amp;amp;amp;amp;amp;#39; age (r = -0.697, p &amp;amp;amp;amp;amp;amp;lt; 0.01). The blood flow velocity in the MCA decreased significantly from 57.5 +/- 13.0 cm/s before the beginning to 48.3 +/- 11.1 cm/s after four hours (n = 18, p &amp;amp;amp;amp;amp;amp;lt; 0.05) and to 43.9 +/- 8.9 cm/s after five hours (n = 9, p &amp;amp;amp;amp;amp;amp;lt; 0.05) of hemodialysis treatment. During hemodialysis treatment, the percentual changes of MFV in the MCA (delta%MFV) were interrelated to the ultrafiltration volume (r = -0.486, p &amp;amp;amp;amp;amp;amp;lt; 0.01), the blood volume (BV%, r = 0.369, p &amp;amp;amp;amp;amp;amp;lt; 0.01) and the percentual changes of the hematocrit (r = -0.358, p &amp;amp;amp;amp;amp;amp;lt; 0.01), of the arterial blood oxygen content (delta%acO2, r = -0.420, p &amp;amp;amp;amp;amp;amp;lt; 0.01) and of the plasma fibrinogen levels (delta%fibrinogen, r = 0.244, p &amp;amp;amp;amp;amp;amp;lt; 0.05). A significant continuous decrease of the MFV in the MCA was observed during hemodialysis treatment, which inversely correlated both with ultrafiltration volume, BV changes and changes of plasma fibrinogen. The ultrafiltration-induced hemoconcentration with concomitant rise of hematocrit and oxygen transport capacity, may partly explain the alterations in the cerebral MFV observed during hemodialysis.
In a 30-year-old male patient systemic lupus erythematosus was diagnosed based on the presence of... more In a 30-year-old male patient systemic lupus erythematosus was diagnosed based on the presence of 8 out of 11 ARA criteria. Disease onset was acute and included renal function impairment with biopsy-proven lupus nephritis (WHO class IV) requiring renal replacement therapy. Although conventional immunosuppressive therapy regimens proved effective in controlling disease activity, all of the administered drugs were accompanied by serious side effects: bilateral femur head necrosis with corticosteroids, allergic skin reaction in response to azathioprine, nephrotoxicity with cyclosporine, nausea and abdominal pain with mycophenolate mofetil and life-threatening septicemia with cyclophosphamide treatment. In search for alternative treatment options, tacrolimus (FK506, trough serum levels 3-6 ng/ml) was started. FK506 was well-tolerated and lupus activity completely resolved within 7 months after initiation of therapy. During 36 months of follow-up no arthritic complaints occurred and renal function stabilized at a serum creatinine of 2.1 mg/dl with negative anti-ds-DNA antibodies and ANA titers. In conclusion, FK506 may be considered as alternative immunosuppressive for maintenance treatment in patients with severe lupus erythematosus and side effects to conventional regimens.
Summary Correlation between postthrombotic syndrome, ADP-induced aggregation and intracellular ca... more Summary Correlation between postthrombotic syndrome, ADP-induced aggregation and intracellular calcium concentration. This study presents a comparison of the ADP-induced platelet aggregation and free cytosolic platelet calcium concentration between patients with postthrombotic syndrome and healthy volunteers. The half maximal effective dose of the platelet aggregation induced by ADP was significantly decreased in postthrombotic syndrome (p<0.005). The mean values were 0.42 µmol/l
Abstract 1 This study was designed to follow changes in plasma catecholamine concentrations durin... more Abstract 1 This study was designed to follow changes in plasma catecholamine concentrations during β-adrenoceptor blockade using doses of antagonists which decreased the mean arterial pressure (MAP) by about 15 mm Hg. Noradrenaline, adrenaline and dopamine were radioenzymatically determined in 34 patients with moderate essential hypertension during an 8 week course of treatment with either pindolol (with intrinsic sympathomimetic activity, ISA) or propranolol (without ISA). Plasma catecholamines were determined before and 1, 7, 28 and 56 days after commencement of treatment and 1 week after discontinuation of treatment. 2 After one day of pindolol therapy plasma catecholamine concentrations were decreased, but no decrease in MAP was observed. After one day of propranolol therapy, however, MAP was decreased, but except for increased levels of adrenaline, plasma catecholamines showed no changes. 3 On the 56th day of therapy both β-adrenoceptor blockers had decreased the MAP. Pindolol therapy had caused a decrease in all three catecholamines whereas propranolol had caused no change except for decreased dopamine levels. 4 One week after cessation of propranolol therapy catecholamines were decreased but the MAP had begun to return to initial values; after cessation of pindolol therapy however, the MAP remained decreased. 5 The dissimilar relationships between blood pressure and catecholamine concentration during pindolol and propranolol therapy are evidence for multiple and different modes of action for β-adrenoceptor blockers with and without ISA. This study demonstrates that catecholamine concentrations were generally decreased during low-dose β-adrenoceptor blocker therapy, with lower catecholamine levels during pindolol treatment than during propranolol treatment.
Acute hepatic failure develops as a disease entity of rather diverse origin. With disease progres... more Acute hepatic failure develops as a disease entity of rather diverse origin. With disease progression, toxic bilirubin levels may cause severe complications which include AV-nodal blockage, cardiac arrhythmia, impaired consciousness, generalized seizures, and status epilepticus. Treatment choices to prevent clinical deterioration comprise of costly and limited available orthotopic liver transplantation, utilization of extracorporeal bioartificial liver support devices and haemoperfusion/plasmaperfusion treatment with activated charcoal/anion exchange filters. Here, we present a patient with acute drug-induced cholestatic hepatitis. Excessively elevated bilirubin levels were accompanied by cardiac and cerebral complications. Extracorporeal resin perfusion treatment (Plasorba, BR-350) was successfully performed over a 50-day period without activation of the coagulation system or side effects. Bilirubin levels were lowered to a minimum of 225 micromol/l, with concurrent clinical improvement. In conclusion, extracorporeal anion exchange plasmaperfusion may be a viable long-term treatment for hyperbilirubinaemic side effects in overt cholestatic hepatitis.
Heparan sulfate proteoglycans are major components of the glomerular basement membrane and play a... more Heparan sulfate proteoglycans are major components of the glomerular basement membrane and play a key role in the molecular organization and function of the basement membrane. Moreover, their presence is essential for maintenance of the selective permeability of the ...
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