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Biomedical subjects

W Franke

Publications and source records attributed to W Franke.

At least 19 recordsLinked to original sources
PubMed1998

Increased autologous blood donation in rectal cancer by recombinant human erythropoietin (rhEPO)

A randomised, placebo-controlled trial was conducted to study whether the subcutaneous administration of recombinant human erythropoietin (rhEPO) increases the donated red cell blood volume in patients with rectal cancer. Patients with resectable rectal cancer and a haemoglobin (Hb) level > or = 12.5/ > 12 g/dl (males/females) were scheduled to receive pre-operatively either erythropoietin (200 U/kg body weight daily) (n = 28) or placebo (n = 26) subcutaneously for 11 days. During this period autologous blood was collected. No serious adverse events were attributed to erythropoietin. 20 of 28 patients treated with rhEPO were able to donate > or = 3 units (71%) compared with 11 of 26 control patients (42%). The mean cumulative volume of red cells donated was 29% higher in the patients who received rhEPO (571 versus 444 ml, P = 0.02). The change in the mean reticulocyte value from baseline to the last pre-operative value was significantly higher in the rhEPO group (10.4 to 61.6/1000 versus 11.0 to 20.1/1000, P = 0.0001). The fall in the mean haematocrit from baseline to the last pre-operative value was significantly lower in the rhEPO group (41.4 to 37.6% versus 41.8 to 34.8%, P = 0.0004). rhEPO increases the ability of cancer patients to donate autologous blood during a short pre-operative period and enhances the restoration of haematological values after the donation period.

Adult↗
PubMed1998

The estimation of efficacy of oral iron supplementation during treatment with epoetin beta (recombinant human erythropoietin) in patients undergoing cardiac surgery.

We estimated the efficacy of oral iron therapy during treatment with rhEPO in patients undergoing cardiac surgery who were contraindicated for autologous blood donation. Seventy-six patients were enrolled in this double-blind, placebo-controlled trial and assigned to the 2 treatment groups (5x500 U/kg body weight rhEPO or placebo intravenously over 14 d before surgery). During the treatment period all patients received 300 mg Fe2+ (iron glycine sulfate) orally per day. rhEPO therapy produced significant increases in hemoglobin concentration (Hb), reticulocyte count, hematocrit (Hct) and the hypochromic red blood cells (HRBC), and a decrease in transferrin saturation (41%) compared to the placebo group before surgery. However, the preoperative increase in HRBC was independent of the baseline ferritin and even correlated positively with the preoperative increase in Hct (r=0.47, p<0.01). In rhEPO patients there were inverse correlations between baseline serum iron and the preoperative increases in Hb (r=-0.39, p<0.05), Hct (r=-0.50, p<0.01) and HRBC (r=-0.53, p<0.001). With this treatment regimen the HRBC appear to reflect the degree of erythropoietic stimulation rather than functional iron deficiency. The preoperative increases in reticulocytes, HRBC and Hb/Hct in patients with ferritin <100 mg/l or transferrin saturation <16% showed no significant difference compared to their complementary groups. The preoperative decrease in storage iron and the inverse correlation between the baseline ferritin and the preoperative change in ferritin (r=-0.94, p<0.0001) in the rhEPO group indicate that the iron requirement for hemoglobin synthesis is probably covered by the breakdown of stored iron and an increase in the rate of absorption of orally administered Fe2+. Intravenous rhEPO treatment with 5x500 U/kg body weight in combination with 300 mg oral Fe2+/d given over 14 d before surgery is a suitable regimen to increase Hb by about 1.61 g/dl and Hct by 0.06.

Administration, Oral↗
PubMed1998

Evaluation of erythropoietic activity on the basis of the red cell and reticulocyte distribution widths during epoetin beta therapy in patients undergoing cardiac surgery.

The changes in the red cell and reticulocyte distribution widths during preoperative treatment with recombinant human erythropoietin (rhEPO) were evaluated in a double-blind, placebo-controlled trial in cardiac surgery patients. The increases in the reticulocyte count, in the hemoglobin and in all distribution widths are the expression of the marked preoperative stimulation of erythropoiesis in the patients treated with rhEPO. Only placebo patients with a hemoglobin < or = 7.5 mmol/l or a transferrin > 4.0 g/l at baseline showed an increase in the red cell distribution width or in the reticulocyte hemoglobin distribution width on oral iron therapy alone. While the reticulocyte count and the distribution widths of red cells in the rhEPO patients decreased postoperatively, only the increases in the distribution widths of reticulocytes after the second postoperative day indicate that stimulation oferythropoiesis had taken place. In patients with a low hemoglobin or a high transferrin the rhEPO therapy should be preceded by iron therapy in order to raise the hemoglobin level and reduce the cost of treatment.

Adult↗
PubMed1998

The safety of treatment with recombinant human erythropoietin in clinical use: a review of controlled studies.

Recombinant human erythropoietin (rhEPO) has now been approved for the treatment of renal anemia, anemia of prematurity, cancer-associated anemia, AIDS-associated anemia and as concomitant treatment for patients with or without autologous blood donation awaiting elective surgery. The purpose of this review is to provide an overview, based on the results of controlled studies, of the anticipated safety profile of rhEPO in various indications and to assess whether treatment with rhEPO influences the incidences of certain adverse events in these indications. The anticipated adverse events differ from indication to indication and generally reflect the corresponding underlying illness. With most indications, no relevant differences in the incidences of adverse events are observed between rhEPO and placebo-control/patients. Only in the rhEPO therapy of renal anemia is an increased incidence of hypertensive events observed in the rhEPO groups, a finding that is not reproduced with the other indications. The controlled studies forming the basis of this review provide no evidence of a relevant increase in the risk of thromboembolic events during rhEPO therapy. Overall, it may be stated that rhEPO treatment, where strictly indicated, is a safe form of therapy. As with any other treatment, the risk of side effects in certain predisposed patients must also be weighed against the desired clinical benefits.

Anemia↗
PubMed1997

Avoidance of allogeneic blood transfusions by treatment with epoetin beta (recombinant human erythropoietin) in patients undergoing open-heart surgery.

In a double-blind, randomized, placebo-controlled trial, we evaluated the ability of epoetin beta (recombinant human erythropoietin) to avoid allogeneic blood transfusions (ABT) and the associated risks in patients undergoing primary elective open-heart surgery and in whom autologous blood donation (ABD) was contraindicated. Seventy-six patients overall were enrolled onto the trial and were randomly assigned to the two treatment groups, 5 x 500 U/kg body weight (BW) epoetin beta or placebo intravenously over 14 days preoperatively. All patients received 300 mg Fe2+ orally per day during the treatment period. Preoperatively, the mean hemoglobin increase was 1.50 g/dL greater in epoetin beta patients than in placebo patients (95% confidence interval, 1.10 to 1.90 g/dL), allowing a rapid return to the baseline value by the seventh postoperative day in most epoetin beta patients. The mean volume of blood collected by intraoperative isovolemic hemodilution was 562 mL (red blood cell mass, 274 mL) in the epoetin beta group and 218 mL (red blood cell mass, 94 mL) in the placebo group, respectively. Only four patients (11%) in the epoetin beta group received an ABT, compared with 19 (53%) in the placebo group (P = .0003). Epoetin beta was most useful in patients with a perioperative blood loss greater than 750 mL, in those with a baseline hematocrit value less than 0.42, and in those aged > or = 60 years. The iron supplementation proved adequate despite the fact that a significant decrease in ferritin (median, 48.1%) and transferrin saturation (median, 40.5%) was observed in epoetin beta patients preoperatively. No influence of epoetin beta therapy on blood pressure, laboratory safety variables, or the frequency of specific adverse events was observed. Intravenous epoetin beta treatment of 5 x 500 U/kg BW in combination with 300 mg Fe2+ orally per day administered over 14 days preoperatively is an adequate therapy for increasing mean hemoglobin levels by approximately 1.50 g/dL and reducing the allogeneic blood requirement in patients undergoing elective open-heart surgery and in whom ABD is contraindicated.

Blood Loss, Surgical↗
PubMed1997

Kinetics of reticulocyte maturity fractions and indices and iron status during therapy with epoetin beta (recombinant human erythropoietin) in cardiac surgery patients.

We evaluated the changes in reticulocyte maturity fractions and indices, as measured by flow cytometry, during preoperative treatment with recombinant human erythropoietin (epoetin beta) in cardiac surgery patients. A total of 72 patients was enrolled in this double-blind, randomized, placebo-controlled clinical trial and assigned to the two treatment groups (5 x 500 U/kg bodyweight epoetin beta or placebo intravenously over 14 days preoperatively). Therapy with epoetin beta produced continuous increases in hematocrit/hemoglobin, in the most mature fraction of reticulocytes (LR), and in reticulocyte count. In the first treatment week there were parallel increases in the fraction of most immature reticulocytes (HR) and in the reticulocyte mean cell volume. During the second week of treatment the reticulocyte mean cell hemoglobin content (CHr) decreased, but CHr was independent of all iron parameters, affecting neither the reticulocyte fractions nor the hematocrit/hemoglobin increase. The total preoperative rise in hematocrit correlated with the rises in LR fraction (P = 0.0270) and reticulocyte count (P = 0.0486) during the first week of treatment. Whereas in the epoetin beta patients the preoperative change in HR fraction showed negative correlations with transferrin saturation at baseline (P = 0.0058) and with the preoperative change in iron (P = 0.0113), the preoperative change in the LR fraction correlated positively with transferrin at baseline (P = 0.0115). Postoperatively, the reticulocyte parameters revealed that the onset of increased stimulation of erythropoiesis did not occur in the placebo patients until the second postoperative day, whereas erythropoietic activity in the epoetin beta patients was much higher during the postoperative period as well, as a result of the preoperative stimulation of erythropoiesis. The reticulocyte parameters measured by flow cytometry permitted an objective analysis of erythropoietic activity during treatment with epoetin beta and in all patients postoperatively. Further studies in various types of epoetin beta therapy are needed in order to clarify the value of these reticulocyte parameters for identification of iron deficiency and optimization of epoetin beta treatment regimen.

Cardiac Surgical Procedures↗
PubMed1997

Evaluation of oxygen availability with oxygen status algorithm in patients undergoing open heart surgery treated with epoetin beta.

We evaluated in a double-blind randomized study the effect of epoetin beta (recombinant human erythropoietin) therapy on oxygen status in patients undergoing cardiac surgery who were contraindicated for autologous blood donation. All 76 patients enrolled in this study were randomized to the two treatment groups (5 x 500 U epoetin beta or placebo/kg body weight intravenously over a 14-day period before surgery) and received 300 mg Fe2+ per day orally before surgery. Before and after surgery the lactate level and the following parameters according to the oxygen status algorithm by Siggaard-Andersen were evaluated: arterial oxygen tension (PaO2), effective hemoglobin concentration (ceHb), arterial oxygen saturation (SaO2), oxygen half saturation tension (p50), red cell 2.3 diphosphoglycerate (2.3 DPG), arterial total oxygen concentration (ctO2), concentration of extractable oxygen (cx), and oxygen compensation factor (Qx). Therapy with epoetin beta led to increases in ceHb, PaO2, ctO2, and cx and to a decrease in Qx before surgery (p < 0.05 for PaO2, p < 0.0001 for the other parameters vs placebo). The cx in patients who received epoetin beta rose by approximately 20%, thus indicating a considerable improvement in O2 delivery. In patients receiving placebo the hemoximetric parameters remained outside the normal limits at all times after surgery, but in the epoetin beta group PaO2, ctO2, cx, and Qx returned almost to their baseline values by the second or fifth postoperative day, even though the frequency of transfusions was significantly higher in the placebo group. Whereas p50 and 2.3 DPG fell in the placebo group after surgery, these two parameters were significantly higher in the epoetin beta group and led to a further increase in cx (from 24% to 38%) versus the placebo group as a result of the right shift in the hemoglobin O2-binding curve. The postoperative incidence and severity of lactic acidosis were higher in the placebo group. Preoperative epoetin beta therapy is a safe way of providing increased extractable O2 (by 24% to 38%) and decreasing the risk of lactic acidosis after surgery. This therapy has a more favorable effect on the O2 binding curve than the transfusion of erythrocyte concentrate and enhances the effect of epoetin beta therapy on the postoperative oxygen status.

Acidosis↗
PubMed1997

The effect of preoperative recombinant human erythropoietin therapy on platelets and hemostasis in patients undergoing cardiac surgery.

In a double-blind, randomized, placebo-controlled trial we evaluated the effects of the administration of recombinant human erythropoietin (5 x 500 U epoetin beta/kg body weight intravenously over a 14-day period before surgery) in patients undergoing cardiac surgery and in whom autologous blood donation was contraindicated on platelet count, platelet distribution width, mean platelet volume (MPV), and certain hemostaseologic parameters. All patients received 3 x 70 IU heparin/kg per day s.c. from 2 days before operation. No thromboembolic events were associated with epoetin beta therapy during the study period. The thrombocytic parameters showed no significant changes in the placebo group before surgery, and the preoperative hematocrit increase in the epoetin beta group was accompanied with an MPV drop (in contrast to the known MPV rise in recombinant human erythropoietin-treated patients with uremia) by a mean of 0.85 fl and a platelet distribution width rise by 3.3% without a significant change in platelet count. In the epoetin beta group the coagulation time (K) of thromboelastogram (TEG) showed an increase from 4.8 to 5.4 minutes by the seventh study day and after the initiation of heparin therapy a further increase to 7.5 minutes. The higher preoperative K increase in the epoetin beta group may partly be a result of the MPV reduction, because smaller platelets are less reactive, a fact underlined by the negative correlation between the preoperative changes of MPV and reaction time of TEG (r = -0.58, p = 0.0148). In contrast, in the placebo group the K of TEG increased only after the start of heparin therapy (from 5.1 to 6.4 minutes). The significant drop in MPV in the epoetin beta group and the higher increase in K of TEG and the other investigated hemostatic parameters do not suggest any increased thromboembolic risk during the preoperative epoetin beta therapy. Therefore this treatment seems to be a safe way for increasing mean hematocrit by approximately 0.06 within the normal range and reducing the homologous blood requirement in patients undergoing elective cardiac surgery.

Adolescent↗
PubMed1994

Lower homologous blood requirement in autologous blood donors after treatment with recombinant human erythropoietin.

The risk of blood-borne diseases has substantially increased the use of autologous blood transfusion. Many autologous donors, however, still need homologous transfusions. To find out whether recombinant erythropoietin (rhEPO) reduces requirements for homologous blood transfusion, we carried out a randomised, controlled trial, in which patients were stratified according to blood volume. We studied 95 autologous blood donors undergoing elective hip surgery. 50 patients were randomly assigned 500 U/kg rhEPO subcutaneously twice a week for 3 weeks, and 45 patients received no treatment (control group). The patients each donated two units of blood before surgery. Only 5 (10%) rhEPO-treated patients received homologous transfusions compared with 16 (36%) controls (p < 0.01). rhEPO was most useful in patients with a blood volume below 4 L and an estimated blood loss below 2 L or with a blood volume of 4-5 L and blood loss of 1-2 L. Continued administration of rhEPO caused no further increase in reticulocyte counts after the fourth injection, which was accompanied by a pronounced depletion of storage iron. rhEPO treatment had no effect on renal function, platelet count, or blood pressure. Subcutaneous rhEPO is an effective and safe way to reduce exposure to homologous blood in autologous donors. Its use can be restricted to a subpopulation of autologous blood donors, which improves the cost-effectiveness of this expensive approach.

Aged↗
PubMed1989

Double-blind controlled crossover study comparing the protective effect of picumast dihydrochloride versus placebo following nasal allergen challenge.

The efficacy of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarine++ + dihydrochloride) in a dosage of 2 mg o.d. (loading dose = 2 b.i.d. over the first three days) vs. placebo after nasal challenge was investigated in 20 patients with allergic rhinitis in a double-blind, controlled crossover study. The primary objective was the decrease in determinable nasal flow as a result of obstruction caused by swelling of the mucous membrane of the nose following nasal challenge with grass pollen. In addition, picumast dihydrochloride's effect on subjective symptoms elicited by nasal challenge, such as "runny nose" and "irritation", was also assessed. Picumast dihydrochloride's ability to inhibit nasal obstruction after challenge was significantly better than that of placebo in statistical terms. Nasal secretion after challenge with grass pollen was far less pronounced with picumast dihydrochloride than placebo. A positive effect on irritation was not seen after nasal challenge. The results of this study show that picumast dihydrochloride inhibits nasal obstruction and secretion in patients allergic to grass pollens following allergen challenge. It is also expected that picumast dihydrochloride will be able to clearly reduce allergic nasal reactions during times of natural, seasonally-high pollen counts.

Adult↗
PubMed1989

Double-blind multicenter controlled clinical study comparing the efficacy of picumast dihydrochloride versus astemizole and placebo in patients with seasonal allergic rhinitis.

The efficacy of picumast dihydrochloride (3,4-dimethyl-7-[ 4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarine dihydrochloride) in a dosage of 2 mg o.d. vs. astemizole (10 mg o.d.) and placebo was investigated in a double-blind, controlled multicenter study. During the first 3 days of treatment, the patients were administered double their assigned dose as loading dose. A total of 119 patients were enrolled in the study, of whom 103 were evaluable for efficacy (picumast dihydrochloride n = 35, astemizole n = 35 and placebo n = 33). The primary objective was the number of patients for whom the investigator scored the effectiveness of study medication as adequate or better over a treatment period lasting at least 4 days. A statistically significantly improved efficacy over placebo was demonstrated by picumast dihydrochloride in terms of the primary objective as was a trend to improved efficacy over astemizole. Observation of the length of participation of the patients in the study up to the point of premature stopping due to inadequate efficacy, adverse events or non-compliance demonstrated that clearly more patients in both active drug groups remained in the study over the planned duration of 28 days compared with patients in the placebo group. In this respect, more patients on astemizole dropped out of the study prematurely compared with patients on picumast dihydrochloride. Serious adverse events did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

[Human transfer factor. I. Production by the great pool technic and the biochemical and immunological characteristics of the preparation].

A great pool procedure for producing human transfer factor preparations from buffy-coats of stored whole blood which has not been used up till now is described. From an initial tool size of about 1,500 units of whole blood the procedure represented makes it possible to gain higher amounts of uniform and in their immunological efficacy in vitro standardizable preparations for controlled long-term therapy studies. By means of various immunological in vitro tests, stimulating as well as suppressing activities of the charges obtained could be identified. Starting from the differentiated immunological effects of various charges of the transfer factor on T-cell populations in vitro, the possibility of influencing T-cell subpopulations through well-conceived therapeutic measures by a transfer factor is discussed.

Adult↗
PubMed1983

[Human transfer factor. II. Clinical results with the large pool transfer factor].

21 patients with diseases due to immunological causes were treated 6 times at an interval of four weeks by administering 5 E TF or 1 E TF each per 10 kg of body weight. TF consisted of 5 different large pool TF charges of 420 to 822 buffy-coats of fresh stored whole blood. Clinical and immunological investigations as well as biochemical ones in the laboratory were made before and after treatment. Large pool TF is clinically effective in 9 from 18 patients and immunologically in 16 from 18 patients. There is a greater effect in immunodeficiencies than in autoimmune diseases. TF is not able to remove the defect for a long time. Repeated administrations are required. TF therapy may be regarded as a substitution therapy. At first, the intervals have to be chosen according to clinical parameters (recidive of the disease or crisis respectively). There is a good compatibility of TF. Side-effects could not be observed. The frequent immunological conversions after score evaluation indicate, however, that in comparison to the clinical appearance the course of the disease must be seen to be much more complex than it can be expressed by in vitro correlates of immunological responses. Statistically ensured correlations of single tests concerning the clinical course could also not be found. Large pool TF provides favourable conditions for controlled therapy trials in order to elucidate those findings of therapy which hitherto had been a subject of controversy (e.g. autoimmune diseases, tumours).

Adolescent↗
PubMed1982

Detection of a human melanoma-associated antigen, p97, in histological sections of primary human melanomas.

The unlabelled antibody technique of Sternberger was used to study the localization in histological sections of human melanoma-associated antigen p97, which is defined by a monoclonal antibody. The antigen was detected in 8 of 10 primary skin melanomas, in 6 of 7 metastatic melanomas and in 2 of 2 compound nevi. It was localized at the cell surface, the cytoplasm and the nucleus always being negative. The antigen was not seen in cells from 3 basal cell carcinomas, 1 squamous cell carcinoma, 1 leiomyosarcoma, or in samples of normal skin (including keratinocytes, connective tissue consisting of collagenous and elastic fibers, fibroblasts, sebaceous glands, blood vessels, smooth muscles, or inflammatory cells such as granulocytes, lymphocytes and macrophages), kidney or lung. There was, however, staining of some cells in the secretory segment of eccrine sweat glands from 2 patients, possibly corresponding to myoepithelial cells. Antigen expression was somewhat variable between cells from different melanomas as well as between individual cells from the same melanoma. The possible diagnostic value of this procedure for identification and classification of melanomas is discussed.

Adult↗