Efficacy, safety and tolerability of valsartan 80 mg compared to irbesartan 150 mg in hypertensive patients on long-term hemodialysis (VALID study).

BACKGROUND: End stage renal disease (ESRD) patients mainly die of cardiovascular disease, and hypertension is regarded as the major risk factor. Valsartan is an angiotensin receptor blocker (ARB) with a well-established efficacy and safety profile in hypertensive patients, but with relatively few data in patients on hemodialysis (HD). The aim of this 2 A 5-week, open-label, multicenter, randomized cross-over study was to investigate whether valsartan (Val) 80 mg is as effective, safe and well-tolerated as irbesartan (Irb) 150 mg in patients with arterial hypertension on long-term hemodialysis. METHODS: After a wash-out of previous ARBs for 1 week, 67 patients (ITT) on long-term hemodialysis, between 18 and 80 years, with mean supine systolic blood pressure (MSupSBP) >or= 140 mmHg and < 180 mmHg were randomized to either Val 40 or Irb 75 for 1 week with forced titration to Val 80 or Irb 150 for another 4 weeks. After a second wash-out period of 1 week, patients were switched from Val to Irb or vice versa for another 5 weeks (1 week low-dose, 4 weeks target dose). The primary objective was non-inferiority of Val versus Irb on predialytic MSupSBP. Secondary objectives were predialytic MSupDBP, adverse events (AEs), laboratory abnormalities, hypotension during and after dialysis and quality of life. BP values are given as mean A+/- SD. RESULTS: Baseline BP values were 158 A+/- 11 / 78 A+/- 13 mmHg (Val) and 161 A+/- 13 / 83 A+/- 10 mmHg (Irb). The predialytic MSupSBP and MSupDBP after 4 weeks of treatment were similar in both treatment groups (Val 150 A+/- 19 / 79 A+/- 13 mmHg; Irb 151 A+/- 16 / 78 A+/- 14 mmHg). Most of the reported AEs were mild to moderate. The percentage of AEs considered by the investigator to be possibly drug-related was similar between both groups: 15.4% in the valsartan group and 20.4% in the irbesartan group. The most common AEs were nausea, muscle spasms and nasopharyngitis. Eight SAEs occurred, four in each treatment group (all not drug-related), including one death (cardiovascular insufficiency) in the Irb group. Laboratory changes were similar in both groups and not clinically relevant. The number of patients with symptomatic hypotension was similar during (9% each) as well as after dialysis (1.3% each). The quality of life data (SF-36) were comparable for each category. CONCLUSIONS: Valsartan 80 mg is as effective, safe and well tolerated as irbesartan 150 mg in hypertensive patients on chronic hemodialysis.

Transluminal removal of an embolized venous catheter fragment with simple means: a case report.

Vascular catheters are associated with complications like infection, thrombosis and stenosis. The embolization of a venous catheter fragment is a rare complication. This report presents a successful transluminal removal of an embolized catheter fragment in a 87-year-old patient who underwent on operative revision with renewed resection and postoperative multiorgan failure. The patient needed a large-bore catheter due to acute renal failure. By replacing the central venous catheter using the Seldinger technique a catheter fragment embolized in the right ventricle. This catheter fragment was removed with a Dormia basket.

Current topics on low-density lipoprotein apheresis.

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lp[a]) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL-apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL-adsorption, and LDL-hemoperfusion. Despite substantial progress in diagnostics, drug therapy, and cardiosurgical procedures, atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia (HLP) therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, however, sometimes the goal of therapy cannot be reached. Mostly, the prognosis of patients suffering from severe HLP, sometimes combined with elevated Lp(a) levels and CHD refractory to diet and lipid-lowering drugs is poor. Hence, in such patients, treatment with LDL-apheresis can be useful. Regarding the different LDL-apheresis systems used, there were no significant differences with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein, or triglyceride concentrations. With respect to elevated Lp(a) levels, however, the immunoadsorption method seems to be the most effective. The published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.

Large bore catheters with surface treatments versus untreated catheters for blood access.

Infection, thrombosis, and stenosis are among the most frequent complications associated with blood contacting catheters. Because these problems are usually related to surface properties of the base catheter material, surface treatment processes, such as ion implantation and ion beam assisted deposition (IBAD) (silver based coatings), can be used to mitigate such complications. Because these ion beam based processes affect only the near-surface region (approximately the outer 1 microm), there is little effect on bulk material properties. This study evaluated silver coated and implanted large bore catheters used for extracorporeal detoxification. In a 186 patient prospective study, 225 large bore catheters were inserted into the internal jugular or subclavian veins. 85 surface treated catheters (Spi-Argent, Spire Corporation, Bedford, MA-USA; n=39 acute catheters, n= 46 long-term catheters) and 28 catheters with surface treatment (Spi-Silicone, Spire Corporation, Bedford, MA-USA) were inserted in 90 patients. 112 untreated catheters placed in 96 patients served as controls (n = 62 acute catheters, n = 58 long-term catheters). After removal, the catheters were cultured for bacterial colonization using standard microbiologic assays. They also were examined using a scanning electron microscope (SEM). Bacterial colonization was observed in 8% of the treated catheters compared with 46.4% of untreated catheters. The SEM investigations showed all treated catheters to possess low thrombogenicity. Results of the study indicate that ion beam based processes can be used to improve thrombus and infection resistance of blood contacting catheters.

Cyclosporin A and therapeutic plasma exchange in the treatment of severe systemic lupus erythematosus.

Despite treatment with intensive immunosuppressive drug regimens, often the prognosis of patients suffering from systemic lupus erythematosus (SLE) is poor. Side effects such as infections and malignancies often occur. It was the aim of this trial to assess the effect of immunosuppression, in particular with cyclosporin, and the efficacy, safety, and clinical utility of intermittent treatment with therapeutic plasma exchange (TPE) in comparison to previous intensive therapy strategies using corticosteroids, azathioprine, and/or cyclophosphamide. In this prospective trial, 28 patients (24 women, 4 men, aged 36.3 +/- 11.8 years at the diagnosis of SLE) were treated for up to 10 years with drug regimens out of corticosteroids, azathioprine, and/or cyclophosphamide. Then, over a period of up to 8 years, in addition to conventional therapies, especially in active stages of the disease with extremely high concentrations of anti-DNA, anti-nuclear antibodies, and circulating immunocomplexes, TPE sessions were carried out depending on symptomatology. In addition, the patients received cyclosporin. Compared with previous treatment modalities, clinical symptoms improved more quickly and more effectively. During the study period of a mean of 5 years, corticosteroids, azathioprine, and cyclophosphamide were reduced by 40 to 100%. No severe side effects were seen. In acute stages of SLE and in forms with persistently high antibody levels, the addition of TPE sessions and cyclosporin as the basic immunosuppressive drug is mostly very effective with regard to improving clinical symptomatology.

Therapeutic plasma exchange in treatment of adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked disorder of metabolism of very long-chain fatty acids (VLCFA) with a frequency of up to 1:20,000 in males. VLCFA C 24:0 and C 26:0 accumulate in the cholesterol ester and ganglioside fraction in plasma and red cells. Symptoms of ALD are ataxia, loss of visual and auditory functions, and cerebral convulsions. Presently, no sure therapeutic approaches are established. Efforts were reported by dietary regimens with VLCFA-restriction and glycerol trioleate and glycerol trierucate intake. In the present trial, we report on a 58-year-old white male suffering from progressive ALD with spastic paraparesis. He has a positive family history back to the 18th century. In this patient, although maximum dietary therapy was applied over a period of 60 months, no normalization of VLCFA C24:0 and C26:0 was reached, and neurological disorders were progressive. As a result, therapeutic plasma exchange (TPE) was applied from 1990 to 1994. Then, for more selective adsorption of VLCFA, dextran-sulfate adsorption (Liposorber, Kaneka, Osaka, Japan) until 1996, and after that, immunoadsorption (Therasorb, Baxter, Munchen, Germany) were used. During these periods (total, 101 months), VLCFA C 24:0 and C 26:0 levels were reduced by 55% and 50% (p < 0.001). The patient experienced a significant improvement in performance and general well-being. No further progression of neuronal disorders was documented. This anecdotal data suggest a very beneficial effect of TPE in treatment of progressive ALD.

Surface treated catheters with ion beam based process for blood access.

Infection, thrombosis, and stenosis are among the most frequent complications associated with blood contacting catheters. Because these problems are usually related to surface properties of the base catheter material, surface treatment processes such as ion implantation and ion beam assisted deposition (IBAD) (silver based coatings) can be used to mitigate such complications. Because these ion beam based processes affect only the near-surface region (approximately the outer 1 microm), there is little effect on bulk material properties. This study evaluated silver coated large bore catheters used for extracorporeal detoxification. In a 135 patient prospective study, 170 large bore catheters were inserted into the internal jugular or subclavian veins. Seventy-eight surface treated catheters (Spi-Argent, Spire Corporation, Bedford, MA, U.S.A.; n = 32 acute catheters, n = 46 long-term catheters) were inserted in 55 patients. Ninety-two untreated catheters placed in 80 patients served as controls (n = 40 acute catheters, n = 52 long-term catheters). After removal, the catheters were cultured for bacterial colonization using standard microbiologic assays. They also were examined using a scanning electron microscope (SEM). Bacterial colonization was observed in 7% of the treated catheters compared with 35.3% of untreated catheters. The SEM investigations showed all treated catheters to possess low thrombogenicity. Results of the study indicate that ion beam based processes can be used to improve thrombus and infection resistance of blood contacting catheters.

Low density lipoprotein apheresis in treatment of hyperlipidemia: experience with four different technologies.

The prognosis of patients suffering from severe hyperlipidaemia (HLP), sometimes combined with elevated lipoprotein (a) levels, and coronary heart disease (CHD) refractory to diet and lipid lowering drugs is poor. A new therapeutic option for such patients is regular treatment with low density lipoprotein (LDL) apheresis. In total 33 patients (16 males, 17 female, aged 43.8+/-14.3 years), suffering from severe HLP resistant to diet and lipid lowering drugs, were treated for 62.3+/-21.3 (range, 1-113) months with LDL-apheresis. Four different LDL-apheresis systems were used: the dextran sulfate adsorption for 28 of 33 (Liposorber, Kaneka, Japan), immunoadsorption for 2 of 33 (Therasorb, Baxter, Germany), LDL-hemoperfusion for 2 of 33 (Dali, Fresenius, Germany), and the immunoadsorption system with special antilipoprotein (a) columns for 1 of 33 patients (Lipopak, Pocard, Russia). Before applying LDL-apheresis, 27 of 33 patients suffered from CHD with severe angina pectoris symptoms, a history of myocardial infarction or coronary artery venous bypass (CAVB). With LDL-apheresis, reductions (p < 0.05) of 46% for total cholesterol, 49% for LDL, 28% for Lp(a), and 38% for triglycerides were reached. Severe side-effects, such as shock or allergic reactions, were very rare (0.5%). In the course of treatment an improvement in general well-being and increased performance were experienced in 29 of 33 patients. In 23 of 27 patients suffering from CHD, a reduction of 60 to 100% of nitrate medication was observed. Regarding the different apheresis systems used, there were no significant differences with respect to the clinical outcome and concerning total cholesterol, LDL, HDL, and triglyceride concentrations. But, in respect to elevated lipoprotein (a) levels, the immunoadsorption method using special anti-lipoprotein (a) columns seems to be the most effective (-57% versus -25% [Kaneka, p < 0.05] or -23% [Baxter, p < 0.05]). The present data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe HLP, refractory to maximum conservative therapy, is effective and safe in long-term application.

Apheresis technologies for prevention and regression of atherosclerosis: clinical results.

The objective of this multicenter trial, which included 28 clinical centers, was to determine if repeated low density lipoprotein (LDL)-apheresis using the Liposorber LA-15 system (Kaneka Corporation, Osaka, Japan) could lead to an additional acute and time averaged lowering of total cholesterol (TC) and LDL-cholesterol (LDL-C) in severely hypercholesterolemic patients whose cholesterol levels could not be controlled by appropriate diet and maximal drug therapy. A total of 6,798 treatments were performed on 120 patients, including eight homozygous familial hypercholesterolemia (FH), 75 heterozygous FH, and 37 unclassified FH or other hyperlipidemias, from 1988 through 1994. The mean TC and mean LDL-C levels at baseline were 410.0 and 333.9 mg/dl, respectively. LDL-apheresis was performed once a week or at least once every 2 weeks in all patients. During treatment with the Liposorber system, the mean acute percentage reduction was 52.6% for TC and 63.1% for LDL-C. Very low density lipoprotein cholesterol (VLDL-C) and triglycerides (TG) were also substantially reduced to 60.6% and 47.5%, respectively. Fibrinogen, a potential risk factor for coronary heart disease (CHD), was reduced by 26.2%. In contrast, the mean acute reduction of high density lipoprotein (HDL) was only 3.4%. The adverse events (AE) were those generally associated with extracorporeal treatments. The most common AE was hypotension, with 69 episodes corresponding to 1% of all treatments reported in 44 of the 120 patients treated. All other kinds of AE occurred in <0.2% of the treatments. The treatment with the Liposorber LA-15 system was overall well tolerated. It should be noted, however, that a more severe type of hypotensive reaction was reported in patients taking concomitant angiotensin converting enzyme (ACE) inhibitor medication. With the exception of such anaphylactoid-like reactions associated with the intake of ACE-inhibitors, the Liposorber LA-15 system represents a safe and effective therapeutic option for patients suffering from severe hypercholesterolemia that could not be adequately controlled by diet and maximal drug therapy.

LDL-apheresis as long-term treatment in severe hyperlipidemia using differing methods.

In 34 patients (18 women, 16 men) suffering from familial hypercholesterolemia resistant to diet and lipid lowering drugs, low density lipoprotein (LDL) apheresis was performed during 72.8 + 43.2 months. Four different systems (Liposorber, 28 of 34, Kaneka, Osaka, Japan; Therasorb, 2 of 34, Baxter, Germany; Lipopak 2 of 34, Pocard, Moscow, Russia; Dali, 2 of 34, Fresenius, St. Wendel, Germany) were used. With all methods, average reductions of 51.9% for total cholesterol, 49.8% for LDL, 69.8% for lipoprotein (a) (Lp(a)), and 58.8% for triglycerides, and an average increase of 9.8% for HDL were reached. Severe side effects such as shock or allergic reactions were very rare (0.5%) in all methods. In the course of treatment, an improvement in general well-being and increased performance were experienced by 31 of 34 patients. Assessing the different apheresis systems used, at the end of the trial there were no significant differences with respect to the clinical outcome experienced by the patients' total cholesterol, LDL, HDL, and triglyceride concentrations. However, to reduce high Lp(a) levels, the immunoadsorption method with special Lp(a) columns (Lipopak) seems to be most effective: -57% versus -25% (Kaneka), -23% (Baxter), and -29% (Dali). The present data demonstrate that treatment with LDL-apheresis of patients suffering from familial hypercholesterolemia resistant to maximum conservative therapy is very effective and safe, even in long-term application.

Therapeutic plasma exchange and cyclosporine in the treatment of systemic lupus erythematosus.

Despite treatment with intensive immunosuppressive drug regimens, often the prognosis of patients suffering from systemic lupus erythematosus (SLE) is poor. Side effects such as infections and malignant tumors often occur. In the present trial, 21 patients (4 male and 17 female, aged 37.9 +/- 12.8 years) suffering from SLE for 9.4 +/- 2.6 years, were treated for 2.3 +/- 1.8 years with drug regimens of corticosteroids, azathioprine and/or cyclophosphamide. Then, over a period of up to 8 years, in addition to conventional therapies, especially in active stages of the disease with extremely high concentrations of anti-DNA-, antinuclear antibodies and circulating immunocomplexes, therapeutic plasma exchange (TPE) sessions were carried out depending on symptomatology. In addition patients received 2.5 +/- 0.6 mg cyclosporine/kg body weight/day. Compared to previous treatment modalities, clinical symptoms improved more quickly and more effectively (p = 0.046). After 5 to 48 (17.5 +/- 13.8) months, cyclosporine was established as a monotherapy for 8 of 21 patients. In the other cases, corticosteroids, azathioprine and cyclophosphamide were reduced by 40 to 100%. No severe side effects were seen. In acute stages of SLE and in forms with persistently high antibody levels, the addition of TPE sessions and cyclosporine as the basic immunosuppressive drug is usually very effective with regard to improving clinical symptomatology.

Plasmapheresis with a substitution solution of human serum protein (5%) versus plasmapheresis with a substitution solution of human albumin (5%) in patients suffering from autoimmune diseases.

Therapeutic plasma exchange (TPE) has been used extensively for over 2 decades to treat a variety of autoimmune and congenital diseases and is now widely accepted. The primary objective of this study was to compare the clinical efficacy of two plasma exchange preparations, human serum protein (HSP) and human albumin (HA). Twenty-four patients in the following disease categories underwent TPE using either HSP (Biseko, 5%) or HA (5%): systemic lupus erythematosus, 8; glomerulonephritis, 8; myasthenia gravis, 2; Guillain-Barré-syndrome, 2; recurrent iritis, 1; pemphigoid, 1; uveitis, 1; and vascular retinitis, 1. There was no statistically significant difference in the average number of TPEs needed in the HSP group (13.5) and HA (13.8) measured over the first 6 weeks of treatment. The secondary parameters, in particular the immunological parameters IgG and IgA, provided evidence that plasma exchange with HSP may have some advantages over HA, and confirmatory studies in a larger group of patients are indicated. Adverse events during TPE occurred in both the HAS group (4 patients) and the HA group (4 patients). However, patients in the HSP group were older (12.3 years), were suffering from more complicated autoimmune diseases, and the number of occasions (days) on which these were reported (6 days) was less than in the HA group (11 days). One patient in the HA group died from septic-toxic circulatory collapse on Day 49 due to an infection with resistant strains of Staphylococcus aureus. Infections in other patients did not occur; all showed considerable improvement in their symptoms and completed the study in good general condition.

Evaluation of microparticles released from an adsorber used for low density lipoprotein apheresis.

Microparticle (MP) released from a DALI 750 Adsorber column for low density lipoprotein apheresis, which is used in a direct hemoperfusion system, was evaluated. The numbers of MP were measured by a light blockage method in the effluents from the column during the rinsing (priming) procedure using a priming solution, and the simulated treatment procedure using a physiologic saline solution as a substitute for whole blood. An unacceptable number of MP were released from the column during the simulated treatment after rinsing with an amount of solution prescribed by the manufacturer. MP concentrations (mean values of three experiments) in the initial 300 ml of the effluent were 639.9, 75.1, and 3.6 pieces/ml for > or = 5 microm, > or = 10 microm, and > or = 25 microm, respectively, and neither the result for > or = 5 microm nor for > or = 10 microm meets the requirement for solutions for injection defined in the United States Pharmacopoeia XXIII or the British Pharmacopoeia of 1993. Furthermore, a large number of MP still remained in the column after all the simulated operations. These findings suggest that the column has a potential to release an unacceptable number of MP into the patient during treatment. Further investigation on the influence of the MP released into the patient's circulation is necessary.

Surface treated large bore catheters with silver based coatings versus untreated catheters for extracorporeal detoxification methods.

Infection, thrombosis, and stenosis are among the most frequent complications associated with blood contacting catheters. Because these problems are usually related to surface properties of the base catheter material, surface treatment processes, such as ion implantation and ion beam assisted deposition (silver based coatings), can be used to mitigate such complications. Because these ion beam based processes affect only the near-surface region (approximately the outer 1 microm), there is little effect on bulk material properties. This study evaluated silver coated large bore catheters used for extracorporeal detoxification. In a 122 patient prospective study, 156 large bore catheters were inserted into the internal jugular or subclavian veins. Seventy-eight surface treated catheters (SPI-ARGENT, Spire Corporation, Bedford, MA; n = 32 acute catheters, n = 45 long-term catheters) were Bambauer inserted in 55 patients. Seventy-eight untreated catheters placed in 67 patients served as controls (n = 35 acute catheters, n = 43 long-term catheters). After removal, the catheters were cultured for bacterial colonization using standard microbiologic assays. They were also examined using a scanning electron microscope (SEM). Bacterial colonization was observed in 15.4% of the treated catheters compared with 44.9% of untreated catheters. The SEM investigations showed all treated catheters to possess low thrombogenicity. Results of the study indicate that ion beam based processes can be used to improve thrombus and infection resistance of blood contacting catheters.

Cyclosporine and therapeutic plasma exchange in treatment of progressive autoimmune diseases.

Despite treatment with intensive immunosuppressive drug regimens, the prognosis of patients suffering from severe progressive autoimmune diseases like systemic lupus erythematosus (SLE), nephrotic syndrome (NS), and Behçet's disease is poor. Side effects (infections and malignant tumors) often occur. In the present trial, 35 patients suffering from autoimmune diseases (SLE, n = 21; NS, n = 10; and Behçet's disease, n = 4) were treated for 3.7 +/- 2.0 years with 2.5 +/- 0.6 mg cyclosporine/kg body weight/day in addition to corticosteroids alone or in combination with azathioprine and/or cyclophosphamide. In active stages of the diseases with extremely high concentrations of anti-ds-DNA-antibodies, antinuclear antibodies, circulating immunocomplexes, and reduced complement concentrations, therapeutic plasma exchange (TPE) has been applied. Compared with previous treatment modalities, significantly (p < 0.05) more effective and rapid reductions of the antibodies were reached. Clinical disorders improved within 1-6 weeks. All patients reported increased performance and a better quality of life. After 1-12 months, the previously required doses of immunosuppressive drugs and the frequency of TPE could be reduced by 40-100%. After 13.4 +/- 11.8 months in 17 of 35 patients (8 with SLE, 5 with NS, 4 with Behçet's disease), cyclosporine was established as the monotherapy. No severe side effects were registered. In treating active stages of severe progressive autoimmune diseases and forms with persistent high antibody levels, the addition of TPE to conventional therapy was very effective, as observed in both clinical and laboratory parameters.

Surface-treated catheters with ion beam-based process evaluation in rats.

Ion beam-based processes such as ion implantation (silicone rubber) and ion beam-assisted deposition (silver-based coatings) affect the outer micron layers of catheter surfaces. These processes were used on the common catheter materials of silicone and polyurethane. In 56 rats, surface (Spi-Silicone and Spi-Argent I and II) catheter segments were implanted for 1, 3, and 6 weeks. After removal, these pieces were investigated for bacterial colonization and fixed for scanning electron microscopic evaluation. As controls, untreated catheter segments were implanted in 28 rats. Bacterial colonization was found in 2.4% in the surface treated catheter pieces versus 7.1% in the control group. The scanning electron microscope investigations showed low thrombogenicity in all of the treated catheters independent of the implantation times.

Low-density lipoprotein apheresis for prevention and regression of atherosclerosis: clinical results.

Hypercholesterolemia can be adequately controlled by appropriate diet and maximum lipid lowering drug therapy in most patients. Nevertheless, there exists a group of patients, including those with familial hypercholesterolemia (FH), who remain at high risk for the development or progression of premature coronary heart disease (CHD). For these patients additional measures such as surgery and low-density lipoprotein (LDL) apheresis have to be considered. The objective of this multicenter trial, which included 30 clinical centers (28 in Germany and one each in Scotland and Luxembourg), was to determine if repeated LDL apheresis using the Liposorber LA-15 system (Kaneka Corporation, Osaka, Japan) could lead to an additional acute and time averaged lowering of total cholesterol (TC) and LDL-cholesterol (LDL-C) in severely hypercholesterolemic patients whose cholesterol levels could not be controlled by appropriate diet and maximum drug therapy. A total of 6,798 treatments were performed on 120 patients, including 8 with homozygous FH, 75 with heterozygous FH, and 37 with unclassified FH or other hyperlipidemias from 1988 through 1994. The mean TC and mean LDL-C levels at baseline were 410.0 mg/dl and 333.9 mg/dl, respectively. LDL apheresis was performed once a week or at least once every 2 weeks in all patients. During treatment with the Liposorber system the mean acute percentage reduction was 52.6% for TC and 63.1% for LDL-C. Very low density lipoprotein cholesterol (VLDL-C) and triglycerides (TG) were also substantially reduced to 60.6% and 47.5%, respectively. Fibrinogen, a potential risk factor for CHD, was reduced by 26.2%. In contrast, the mean acute reduction of high density lipoprotein (HDL) was only 3.4%. During the course of the treatment, the time averaged levels of TC and LDL-C were reduced by approximately 39% and 50%, respectively, compared to baseline levels. The adverse events (AEs) were those generally associated with extracorporeal treatments. The most common AE was hypotension, with 69 episodes corresponding to 1% of all treatments reported in 44 of the 120 patients treated. All other kinds of AEs occurred in less than 0.2% of the treatments. The treatment with the Liposorber LA-15 system was overall well tolerated. It should be noted, however, that a more severe type of hypotensive reaction associated with flush, bradycardia, and dyspnea was reported in patients taking concomitant angiotensin converting enzyme (ACE) inhibitor medication. Except for such anaphylactoid-like reactions associated with the intake of ACE inhibitors, the Liposorber LA-15 system represents a safe and effective therapeutic option for patients suffering from severe hypercholesterolemia that could not be adequately controlled by diet and maximum drug therapy.

Plasmapheresis in treatment of adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked disorder of metabolism of very long chain fatty acids (VLCFAs) with a frequency of up to 1:20,000 in males. VLCFAs C24:0 and C26:0 accumulate in the cholesterol ester and ganglioside fraction in plasma and red cells. Symptoms of ALD are ataxia, loss of visual and auditory functions, and cerebral convulsions. Up to the present, no sure therapeutic approaches have been established. Efforts were reported by dietary regimens with VLCFA restriction and glyceroltrioleate and glyceroltrierucate intake. In the present trial, we report a 55-year-old Caucasian male suffering from progressive ALD with spastic paraparesis. He has had a positive family history since the eighteenth century. In this patient treated with maximum dietary therapy over a period of 60 months, no normalization of C24:0 and C26:0 was reached, and neurological disorders were progressive. As a result, plasmapheresis was applied during the period 1990-1994 and since then for more selective adsorption of VLCFAs, dextran sulfate adsorption (Liposorber, Kaneka, Japan). During this period (64 months), C24:0 and C26:0 levels were reduced by 54.5% and 51.8%, respectively (p = 0.0001). The patient experienced a significant improvement in performance and general well-being. There has been no further progression of neuronal disorders to document.

LDL apheresis in clinical practice: long-term treatment of severe hyperlipidemia.

Thirty patients (13 males, 17 females) suffering from familial hypercholesterolemia resistant to diet and lipid-lowering drugs were treated for 48.7 +/- 19.2 months (range, 2-87 months) with low density lipoprotein (LDL) apheresis. Three different systems (dextran sulfate adsorption for 27 of 30 [Kaneka, Liposorber, Japan], immunoadsorption system for 2 of 30 [Baxter, Therasorb, Germany], immunoadsorption system with special lipoprotein a [Lp(a)] columns for 1 of 30 patients [Lipopak, Pocard, Russia]) were applied. Before LDL apheresis 24 of 30 patients suffered from coronary heart disease (CHD) with angina symptoms. With LDL apheresis, reductions of 46% for total cholesterol, 49% for LDL, 30% for Lp(a), and 38% for triglycerides were reached. Severe side effects such as shock or allergic reactions were very rare (0.5%). In the course of treatment, an improvement in general well-being and increased performance were experienced in 27 of 30 patients. A 60 to 100% reduction of nitrate medication was observed in 17 of 24 patients. Regarding the different apheresis systems used, at the end of the trial there were no significant differences with respect to the clinical outcome experienced by the patients and concerning total cholesterol, LDL, high density lipoprotein, and triglyceride concentrations. But to reduce high Lp(a) levels, the immunoadsorption method with special Lp(a) columns seems to be the most effective (-57% versus 25% [Kaneka] and 23% [Baxter]). The present data clearly demonstrate that treatment with LDL apheresis of patients suffering from familial hypercholesterolemia, resistant to maximum conservative therapy, is very effective and safe, even in long-term application.

Cyclosporin and plasmapheresis in treatment of progressive systemic lupus erythematosus (pSLE).

The prognosis of patients suffering from progressive systemic lupus erythematosus (pSLE) is poor, despite treatment with intensive drug regimens with combinations of corticosteroids, azathioprine and cyclophosphamide. Side-effects such as infections and malignomas often occur. In the present trial, 21 patients (four male, 17 female, aged 37.9 +/- 12.8) suffering from pSLE for 9.4 +/- 2.6 years, were treated for 2.3 +/- 1.8 years with drug regimens as mentioned above. Then, over a period of 6.4 +/- 2.6 (range 1-8) years, in addition to conventional therapies, cyclosporin (2.5 +/- 0.6 mg/kg body wt/d) and, in active stages of the disease with extremely high concentrations of anti-ds-DNA-, anti-nuclear antibodies and circulating immunocomplexes, plasmapheresis (therapeutic plasma exchange (TPE)) have been applied. Compared with previous treatment modalities, significantly (P < 0.05) more effective and rapid reduction of antibodies was achieved. Clinical symptoms improved within 2 to 4 weeks. Under the new therapeutic regimen all patients reported increased performance and a better quality of life. After 5 to 48 (17.5 +/- 13.8) months, cyclosporin was established as mono-therapy for 8/21 patients. In] the other cases, corticosteroids, azathioprine and cyclophosphamide were reduced by 40 to 100%. No severe side-effects were seen. In acute stages of pSLE and in forms with persistently high antibody levels, the addition of TPE to conventional therapy was very effective, with regard to improving both clinical and laboratory parameters.