Biomedical subjects

Wolfgang Ramlow

Publications and source records attributed to Wolfgang Ramlow.

7 recordsLinked to original sources

PubMed2005

Pilot clinical study of Adacolumn cytapheresis in patients with systemic lupus erythematosus.

The aim of this study is to investigate the clinical effects of cytapheresis using the Adacolumn system (selective removal of circulating monocytes and granulocytes by means of an extracorporeal type column) in patients with active systemic lupus erythematosus (SLE). An open uncontrolled multicenter pilot study was conducted in 18 SLE patients who were showing a SLEDAI score of 8 or more under conventional medication. Patients with lupus nephritis (>class 1, WHO classification) were excluded. Extracorporeal cytapheresis with the Adacolumn system was administered once a week for five consecutive weeks. The efficacy of the treatment was evaluated using the SLEDAI for 10 weeks after the first cytapheresis session. The median SLEDAI decreased from 16 at baseline to six at week 11 (10 weeks after the first apheresis) (p<0.001). Significant improvements in musculoskeletal and dermal systems were observed. Arthritis and alopecia were present in 14 and nine patients at baseline and this number decreased to five and one patients, respectively by week 11. Three mild and one moderate adverse events out of the 42 reported events were judged 'probably related' to the treatment; no serious adverse events were reported. Selective removal of monocytes and granulocytes from the blood in an extracorporeal circulation system was associated with clinical improvement in this small series of patients with SLE. Since this approach seems not to have the disadvantages of pharmacological immunosuppression, further controlled studies of Adacolumn cytapheresis are warranted in SLE.

Adult↗

PubMed2005

In vitro and in vivo evaluation of Adacolumn cytapheresis in healthy subjects.

Adacolumn is a medical device for adsorptive cytapheresis. It has been developed for selective adsorption of granulocytes and monocytes from peripheral blood of patients with immune disorders, such as autoimmune diseases and chronic inflammatory diseases. A double blind sham-controlled crossover study design was used in order to evaluate in vivo biological responses of leukocytes as well as biocompatibility during and after Adacolumn cytapheresis in healthy volunteers. In addition, experiments were undertaken to further evaluate leukocyte reactions to Adacolumn carrier (G-1: cellulose diacetate) beads in vitro. Six healthy volunteers, 4 males and 2 females, with a mean age of 26.7 years were randomly assigned to one of the two treatment arms in a crossover fashion. Three subjects received a single Adacolumn treatment, followed by a single sham treatment at an interval of 7 days. The other three subjects received the two treatments in reverse order. All subjects were followed up 7 days after the last treatment. Additionally, in vitro investigations were carried out using blood from the healthy donors to examine the effect of G-1 beads on granulocyte functions. In vitro exposure of human peripheral blood to G-1 beads caused downregulation of L-selectin expression and upregulation of Mac-1 expression on granulocytes, leading to a marked reduction of adhesive capacity of granulocytes to endothelial cells. The exposure also led to decreased granulocyte chemotactic activity to IL-8. The number of granulocytes and monocytes clearly decreased during Adacolumn cytapheresis. Granulocytes showed marked phenotypic changes of L-selectin(Low) and Mac-1(Hi) after passing through Adacolumn in vivo. Expression of TNF-alpha and chemokine receptors was downregulated. In addition, TNF-alpha and IL-1beta producing capacity of peripheral blood leukocytes was decreased after Adacolumn cytapheresis and these changes lasted even one week after the cytapheresis. The level of complement fragments, C3a and C5a, increased, while bradykinin concentration did not change during Adacolumn cytapheresis. Exposure of human peripheral blood to G-1 beads, both in vitro and in vivo, caused a significant reduction of adhesive capacity and proinflammatory cytokine producing capacity of peripheral blood leukocytes. Such changes were not observed after sham apheresis. Despite complement activation, tolerability of Adacolum cytapheresis was not influenced. These findings may at least partly explain the beneficial effect of Adacolumn cytapheresis in the treatment of autoimmune diseases.

Adult↗

PubMed2002

Extracorporeal fibrinogen adsorption--efficacy, selectivity and safety in healthy subjects and patients with foot ulcers.

The elimination of fibrinogen from plasma improves plasma viscosity and whole blood viscosity. For extracorporeal adsorption of fibrinogen the pentapeptide gly-pro-arg-pro-lys was coupled to sepharose CL-4B. Columns containing 100 ml of coupled sepharose CL-4B were used to eliminate fibrinogen from the plasma of 8 healthy male subjects (mean age 27.4 +/- 4.3 years, height 180.9 +/- 8.3 cm, weight 85.1 +/- 13.6 kg). Four treatments were performed in each proband (days 1, 2, 4 and 7). Plasma fibrinogen concentration was lowered from 221.1 +/- 39.0 to 123.5 +/- 21.7 mg/dl (2275 +/- 477 ml plasma treated) by the first treatment, from 172.8 +/- 42.3 to 105.6 +/- 16.5 mg/dl (1609 +/- 761 ml) by the second, from 140.5 +/- 13.8 to 98.8 +/- 8.6 mg/dl (1224 +/- 118 ml) by the third and from 160.2 +/- 23.6 to 106.4 +/- 9.7 mg/dl (1513 +/- 521) by the fourth. Plasma viscosity was improved from 1.40 +/- 0.18 mPa s before the first treatment to 1.23 +/- 0.06 mPa s after fourth treatment, whole blood viscosity from 4.49 +/- 0.36 mPa s to 3.83 +/- 0.27 mPa s (P < 0.01). No clinical side effects and no clinically relevant change of laboratory parameters including in vitro tests on thrombocyte function were observed. Seven men and three women (48-75 years old, 9 patients suffered from diabetes mellitus, one patient from peripheral arterial occlusive disease, 5 patients were on regular hemodialysis) were treated by fibrinogen adsorption. Each column contained 135 ml of coupled sepharose CL-4B. Treatments were scheduled on day 1, 2, 4, 6, 8, 10, 13, 16, 19, 22, 25 and 28. 144 treatments with fibrinogen adsorption were performed. No clinical side effects due to the fibrinogen-adsorption procedure were observed. In these 10 patients the fibrinogen concentration before the first treatment was 473.7 +/- 183.7 mg/dl. In the first treatment session it was lowered to 241.4 +/- 125.8 mg/dl by treating 4270 +/- 1180 ml of plasma. In the following 134 treatments the pre-treatment concentration of fibrinogen was 262.6 +/- 83.4 mg/dl, the post-treatment concentration was 120.6 +/- 37.2 mg/dl. The mean volume of plasma treated was 3737 +/- 1643 ml, the mean duration of a treatment session (except the first treatment) was 143.7 +/- 63.1 min. In 7 patients a mean post-treatment fibrinogen concentration of < or = 123 mg/dl was obtained, in the other patients 133, 177 and 184 mg/dl. Yet, the decrease of fibrinogen concentration was also pronounced in these 3 patients: -82%, -67%, and -73%, respectively. Accelerated wound healing was observed in 9 of the 10 patients. In conclusion, affinity chromatography using the pentapeptide gly-pro-arg-pro-lys is an effective, selective and safe procedure to lower fibrinogen concentration in plasma thereby improving blood viscosity. It could be a therapeutic option in severe blood vessel disease where drug therapy is not sufficient and invasive procedures like bypass or angioplasty cannot be applied.

Adolescent↗

PubMed2002

Comparison of two filter combinations for low-density lipoprotein apheresis by membrane differential filtration: a prospective crossover controlled clinical study.

Membrane differential filtration is an accepted procedure for the extracorporeal removal of low-density lipoprotein (LDL). Reduction rates largely depend on the nature of the membranes and are ideally evaluated in a crossover study design. Four patients who had been treated by LDL apheresis for at least 6 months were included. Six consecutive weekly sessions (40 ml plasma/kg body weight) were scheduled per system (Plasmacure PS06/Evaflux Eval 5A [Kuraray] versus Plasmaflo OP05W/Cascadeflo AC1770 [Asahi]). Laboratory measurements indicated reductions of plasma concentrations for fibrinogen (37% [Kuraray] versus 44% [Asahi]), IgG (15% versus 20%), IgA (24% versus 28%), IgM (63% versus 53%), and total protein (11% versus 16%). Total cholesterol was eliminated by 52% versus 49%, LDL by 67% versus 66%, triglycerides by 56% versus 41%, and high-density lipoprotein by 10% versus 20%. Three therapies employing the Asahi filter combination were terminated prematurely due to saturation of the plasma fractionator. In conclusion, despite similar physical properties, the membranes differ significantly concerning selectivity and sensitivity to saturation.

Aged↗

PubMed2002

Selective removal of circulating immune complexes from patient plasma.

The principle of a patient-specific immunoadsorber (PsIA) is demonstrated. Studies with model systems (HSA/anti-HSA) on immobilization, stability, and leakage form the basis for the presented fast-performance liquid chromatography (FPLC) and batch experiments, which were conducted using two different protein A adsorbers and autologous and heterologous PsIA systems. Experiments to determine the binding capacity of protein A adsorbers and PsIAs are described. In all experiments, the adsorption of plasma IgG, total protein, and C1q and C3d circulating immune complexes were measured. Plasma of patients with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus) was investigated. Analysis was performed in both the initial plasma and the flow-through or supernatant. Results of the investigations using FPLC and batch experiments were compared. Autologous PsIA systems are suitable for the selective removal of elevated levels of circulating immune complexes in the plasma.

Antigen-Antibody Complex↗

PubMed2002

Online hemodiafiltration versus acetate-free biofiltration: a prospective crossover study.

Online hemodiafiltration (online HDF) and acetate-free biofiltration (AFB) are 2 innovative renal replacement therapies. Convincing evidence has shown that both techniques are superior to conventional hemodialysis in many aspects. The aim of the present investigation was to compare online HDF and AFB in 12 stable maintenance hemodialysis patients in a prospective, randomized crossover trial. Twelve stable dialysis patients, age 49.7 +/- 11.3 years and on dialysis for 83.5 +/- 76.7 months, were treated prospectively and randomly by either AFB, predilution HDF (pre-HDF), or postdilution HDF (post-HDF) for a total of 36 weeks using exclusively F60S high-flux dialyzers. Routine blood biochemical tests, bone metabolism parameters, and clearance for both small and larger molecular weight substances were measured at defined intervals. During the trial period inter- and intradialysis symptoms, e.g., hypotensive episodes and intradialysis arterial blood gas analyses, were recorded. Both online HDF and AFB were well accepted by the overwhelming majority of patients and also by the dialysis staff. Pretreatment sodium, total and ionized calcium, chloride, bicarbonate, and urea did not differ within or between the 3 treatment groups. Potassium increased slightly in HDF patients while phosphate and beta2-microglobulin (beta2-M) decreased in all groups. After dialysis, AFB patients exhibited a significantly higher bicarbonate concentration and lower potassium level when identical potassium concentrations in dialysate were used. Patients receiving AFB manifested less intradialysis partial pressure of oxygen drop and partial pressure of carbon dioxide rise than those on HDF treatments. HDF treatments could afford higher single-pool and double-pool Kt/V, higher effective urea and beta2M clearance, and lower total interdialysis symptom scores than the AFB treatment method. While bone metabolism parameters did not differ between the 3 dialysis modalities, some parameters such as deoxypyridinoline in HDF and osteocalcin, pyridinoline, and deoxypyridinoline in AFB deteriorated at the end of the crossover study. Aluminum concentration decreased progressively to about one-third of prestudy values at the end of the study with all 3 treatments. AFB was associated with a lower predialysis mean arterial pressure (MAP), a smaller drop in MAP during treatment, and similar hypotension episodes compared with the 2 HDF treatments. Albumin concentration showed a trend to decrease during the first 2 months of the trial period followed by a slight increase thereafter but still significantly lower than initial value at the end of crossover. Both online HDF and AFB share most of the features of optimal renal replacement therapy. Online HDF is superior to AFB in such aspects as increased delivered dialysis dose both for small and larger molecular weight toxins and less interdialysis symptoms. On the other hand, AFB is associated with a smaller effect on arterial blood gas values and improved intradialysis hemodynamic tolerance. Some dialysis-related symptoms and complications in the case of our AFB practice could be attributable, at least in part, to low dialysate calcium level.

Adult↗

PubMed2002

Changes in lymphocytic cluster distribution during extracorporeal immunoadsorption.

The success of apheresis treatment is often measured as a decrease in the detected antibodies and an improvement in different disease-related scores. Sometimes, however, the seriousness of the disease does not correlate with the antibody level. During a period of 8 years, 15 patients (3 myasthenia gravis, 1 multiple sclerosis, 2 systemic lupus erythematosus, 3 alloimmunized kidney transplant, 6 rheumatoid arthritis) were treated by protein A immunoadsorption. Lymphocyte subpopulations (activated T cells, cytolytic T cells, B cells, natural killer cells) and inflammatory proteins (ferritin, C-reactive protein, alpha1-antitrypsin, alpha2-macroglobulin) were analyzed. After observing clinical outcomes, the patients could be divided into 2 groups, respectively: Group 1, responding patients with remission of disease; and Group 2, delayed-responding patients, who required chronic treatment. Group 1 patients characteristically showed a greater increase in activated T and cytolytic T cells which correlated with a greater decrease of B cells. It might be possible that protein A immunoadsorption induced immunomodulation. Further immunological investigation is required to verify these findings.

Adult↗