[The motivation to use complementary medicine healing methods. Study of a general internal medicine and orthopedic patient sample]. / Uber die Motivation zur Verwendung komplementärmedizinischer Heilmethoden. Untersuchung an einem allgemein-internistischen und orthopädischen Patientenkollektiv.

436 patients from two different clinics of internal medicine and one orthopaedic unit were asked to fill a questionnaire on their attitude towards and use of alternative medicine. Of the 272 questionnaires returned, 235 could be used for analysis. 42.6% of all analysed persons confirmed use of alternative medicine. About half of them were motivated to do so by their nursing staff. Homeopathy was by far the most frequently used method. Persons who used alternative medicine were characterised by a distinct environmental awareness and regular sports activity. They had also often had positive experience of alternative methods in childhood. On the other hand, age, sex, education, duration of the treated disease and success of conventional therapy did not correlate significantly with the use of alternative medicine. An essential motive for the need to seek help by alternative therapists was the opinion that conventional forms of treatment would concentrate too much on the purely physical side of a health problem. All in all, users of alternative medicine did not seek confrontation with conventional medicine but rather sought a real complement to conventional forms of treatment.

Use of epoetin alfa in autologous blood donation programs for patients scheduled for elective cardiac surgery.

The optimum dosage of subcutaneous (s.c.) epoetin alfa was assessed in a double-blind study in 31 patients scheduled for cardiac surgery. Patients received a total of four doses of either epoetin alfa 150 IU/kg (n = 11), epoetin alfa 300 IU/kg (n = 10), or placebo (n = 10) administered as single s.c. injections at weekly intervals starting 23 days prior to surgery. AB was collected with isovolemic replacement prior to each of the first three doses of medication. During the AB donation period, Hb levels decreased significantly (P < .05) from baseline to surgery in the placebo group (16.5%), compared with no significant decrease in either of the epoetin alfa groups (8.1% and 9.7% in the 150 IU/kg and 300 IU/kg groups, respectively). In addition, the difference between groups with regard to the decrease in Hb level reached statistical significance (P < .05) for the 150 IU/kg group versus placebo. Epoetin alfa treatment was also associated with significantly higher reticulocyte counts and serum erythropoietin levels in the preoperative period compared with placebo.

Human endothelial cells suppress prothrombin activation in nonanticoagulated whole blood in vitro.

Human endothelial cells cultivated on polystyrene microcarrier beads were used to study endothelial anticoagulant activity in vitro. Spontaneous whole blood coagulation was inhibited by endothelial cells on microcarriers at a surface to volume ratio of 16 cm2/ml blood. Thrombin activity generated in nonanticoagulated whole blood during 1 hour and assessed by its fibrinogen clotting effect was reduced by 87% in the presence of endothelial cells. Consistent with this observation, prothrombin fragment1+2, fibrinopeptide A, and thrombin-antithrombin III-complex release during the same period of time were inhibited by 81%, 47%, and 88%, respectively. Immunoblotting analysis of cell-free supernatants derived from the same samples demonstrated that prothrombin activation was strongly suppressed in the presence of endothelial cells. Furthermore, the incubation of nonanticoagulated whole blood with endothelialized beads for only 5 minutes after venipuncture was sufficient to prevent subsequent prothrombin activation in the cell-free supernatants of the same whole blood sample after centrifugation. These findings suggest that interruption of the coagulation cascade is probably one major mechanism of endothelial anticoagulant activity in vivo.

[Hypercalcemia as an emergency]. / Hyperkalzämie als Notfall.

The hypercalcemic syndrome and the relation of serum calcium with the concentration of ionic calcium and albumin are shortly described. The pathogenetic significance of local, cytokine-induced bone destruction and of the osteoclast-stimulating effect by "parathyroid hormone related peptide" leading to "humoral hypercalcemia of malignancy" is underscored. In a hypercalcemic emergency the therapeutic strategy should combine adequate rehydration and induction of calciuresis by furosemide and the intravenous application of a rapid-onset, calcium lowering substance such as calcitonin and, simultaneously, of a slow-onset, long-acting bisphosphonate such as pamidromate, which may be infused as a single dose.

[Blood parasitosis--mechanisms and limitations of a species-alien coexistence]. / Blutparasitosen--Mechanismen und Grenzen artfremder Koexistenz.

Human proto- and metazoa, which spend a part of their life-cycle within erythrocytes or extracellularly in human blood or in monocyte-derived macrophages, are considered as blood parasites. In spite of their individually widely differing habitat, they elicit a common hematological syndrome essentially consisting in hemolytic anemia and splenomegaly. Furthermore, some basic factors of host/parasite interaction are very similar: (1) Specific cell attachment through receptor/ligand mechanisms such as the integrin/RGD-oligopeptide system, (2) competition for essential nutrients such as iron, which may be influenced therapeutically to the disadvantage of the parasite by the use of iron chelators, and (3) provocation of host defense through T-cell dependent, cytokine-mediated macrophage activation.

[Iron and iron-binding proteins in the differential diagnosis of pleural effusion]. / Eisen und eisenbindende Proteine in der Differentialdiagnose von Pleuraergüssen.

Iron, iron-binding capacity, lactoferrin and total protein were determined in the plasma and pleural fluid of 30 patients with cardiac failure (n = 10), infectious/inflammatory disease (n = 9) and metastatic carcinoma (n = 11). In 16 patients pleural transferrin and ferritin was also measured. Plasma iron and total iron-binding capacity were reduced in inflammatory and neoplastic disease, whereas hyposideremia with normal iron-binding capacity was seen in patients with heart failure. Plasma lactoferrin was reduced in metastatic carcinoma. Exudates (protein greater than or equal to 30 g/l; infectious/inflammatory: 9/9, carcinomatous: 10/11) had significantly higher iron, lactoferrin, transferrin and ferritin concentrations than transudates (protein less than 30 g/l; heart failure: 10/10, carcinomatous: 1/11). Statistically, infectious/inflammatory exudates could be distinguished from neoplastic exudates by a higher median iron concentration (non-parametric Wilcoxon-Mann-Whitney test). Overlap of the respective ranges, however, did not allow a clear-cut differential diagnosis in individual cases. Pleural lactoferrin concentrations, on the other hand, correlated with the pleural granulocyte count and nonspecifically reflect the degree of granulocytic inflammation. Positive pleural/plasma correlations of protein and of iron concentrations were found in exudates only. Within exudates and transudates, on the other hand, total protein correlated with transferrin but not with iron concentrations. Therefore, and because of the substantially higher pleural/plasma ratio for iron than for transferrin concentrations, a quantitatively important, non-transferrin bound iron pool in pleural fluids, most probably ferritin, must be assumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibacterial prophylaxis with lactoferrin in neutropenic patients.

The prevention of enterogenic infection by human lactoferrin was tested in five neutropenic patients receiving chemotherapy for acute myelogenous leukemia. Lactoferrin did not significantly delay the onset of infection but reduced its duration and severity as judged from the course of fever. Compared with nine matched controls, lactoferrin-treated patients had a lower incidence of bacteremia on the whole and of gram-negative bacteremia in particular.

Hyperlactataemia, hyperkalemia and heart block in acute iron overload: the fatal role of the hepatic iron-incorporation rate in rats on ferric citrate infusions.

An animal model is presented that provides constant and controllable conditions for approaching gradually, and within reasonable time, different stages of iron overload and, probably, an iron-induced mitochondrial disorder. Thirty-five rats were infused with ferric citrate, sodium citrate and saline at constant rates for 6-24 h. In the 200-3200 micrograms Fe h-1 loading range, the iron-incorporation capacity of the liver was not saturable and the fractional iron uptake by the liver remained at approximately 30% even at a loading rate of 3200 micrograms Fe h-1. Up to a loading rate of 200 micrograms Fe h-1, iron storage was not associated with toxic effects. Beyond this loading rate, however, the liver was no longer able to prevent a massive plasma iron increase on one side and hyperlactataemia on the other. These signs most probably represent hepatocellular decompensation with respect to a critical iron-storage rate. The product of plasma iron x exposition time was significantly correlated with increased plasma lactate levels (r = 0.89, P less than 0.005), whereas increased plasma iron levels per se were not. Hyperlactataemia was associated with hyperkalaemia and progressive cardiac conduction defects leading to cardiac arrest at lactate concentration of 9.1 +/- 4.3 mmol l-1. The hypothesis is discussed that toxicity in acute iron overload may entirely be due to hepatocellular (mitochondrial) damage, and not to multiple organ iron overload.

Sex-related differences in hematological values. A study on the erythrocyte and granulocyte count, plasma iron and iron-binding proteins in human transsexuals on contrasexual hormone therapy.

Hematological data known or supposed to be influenced by individual sex hormones were evaluated in 18 untreated transsexuals (TS) and in 20 castrated or non-castrated TS on androgen and estrogen treatment, respectively. Profiting from a situation of clinically controlled hormonal sex-transformation it was tested, whether the circulating erythrocyte and granulocyte mass and iron metabolism are linked to a male and female sex-hormone constellation. The erythrocyte and granulocyte counts were significantly higher in untreated males and treated female-to-male TS than in untreated females and treated male-to-female TS. The unexpected finding of sex hormone-dependent granulocyte fluctuations was corroborated by parallel concentration changes of lactoferrin, a granulocyte-derived plasma protein. Iron metabolism as judged from plasma iron, total iron-binding capacity and serum ferritin was unaffected by sexual transformation. Plasma iron and the total iron-binding capacity did not differ significantly in untreated and treated TS of either type. The serum ferritin concentration, however, was significantly lower in untreated as well as in virilized females than in untreated and in feminized males, but was not significantly changed by long-term androgen or estrogen treatment. The present study demonstrates the potential of human transsexualism as a model for the study of sex-related biological processes.

Plasmalactoferrin and the plasmalactoferrin/neutrophil ratio. A reassessment of normal values and of the clinical relevance.

In healthy subjects normal plasmalactoferrin (PLf) concentrations were found to be 0.206 +/- 0.06 mg/l in 49 men and 0.148 +/- 0.06 mg/l in 62 women. A highly significant correlation of PLf with the number of circulating neutrophils (PMN) and a PLf/PMN relationship suggesting proportionality was demonstrated. Among 73 patients absolute PLf concentrations were significantly increased in septicemia, cirrhosis of the liver and tumors with liver metastases, decreased in localized infection, tumors without liver involvement, iron deficiency and acute hepatitis B, and normal in acute myocardial infarction. The PLf/PMN ratio, on the other hand, was normal in liver cirrhosis, hepatitis B and in a part of the patients with septicemia and tumor disease with liver involvement. The ratio was increased in a part of the septicemic patients, and decreased in the remaining disease types. Positive PLf/PMN correlations were found in myocardial infarction, septicemia and liver cirrhosis, whereas a very close, negative correlation existed in acute hepatitis B. These findings are discussed on the basis of existing knowledge on lactoferrin physiology, the intravascular fate of PMN and the RES function.

[Rational iron therapy]. / Rationale Eisentherapie.

After a short outline of internal iron metabolism, some principles of iron absorption, and especially the difference between heme and non-heme iron absorption and some food interactions, are presented. Particular emphasis is placed on absorption, since in most cases of iron deficiency oral substitution is the rational therapy of choice. Finally, noninvasive methods indicating increased iron demand are recalled, and recommendations as to the type, dose, duration and evaluation of oral substitution therapy are made.

Oxidative radioiodination damage to human lactoferrin.

Oxidative iodination of human lactoferrin (Lf) as commonly performed by using the chloramine-T, the Iodogen or the lactoperoxidase method produces an unreliable tracer protein because of excessive and heterogeneous polymer formation. Before iodination a minor tetramer fraction may be demonstrable in iron-saturated Lf only. Iodination-induced polymerization of iron-poor as well as iron-saturated Lf occurs independently of the presence or absence of 10 mM-EDTA and the 125I-/Lf molar ratio used for iodination. 125I-Lf polymers are mainly covalently linked, as suggested by the lack of substantial dissociation in SDS/polyacrylamide-gel electrophoresis. Damage to the 125I-Lf monomer may be another consequence of oxidative iodination. This is demonstrated in SDS/polyacrylamide-gel electrophoresis where 50% of the radioactivity of apparently normal monomer (Mr 75,000) is displaced to a lower-Mr region (30,000-67,000) after reduction with dithiothreitol. Non-oxidative iodination by the Bolton-Hunter technique produces an antigenetically stable tracer that is not being subjected to polymerization and monomer degradation as judged by high-performance gel chromatography and SDS/polyacrylamide-gel electrophoresis with and without dithiothreitol treatment. It is concluded that oxidation in itself leads to covalent non-disulphide cross-linking between human Lf molecules and, possibly, to intramolecular peptide-bond breaking becoming unmasked under reducing conditions. In biological experiments with human 125I-Lf this problem should be carefully considered.

[The effect of hormonal contraceptives and pregnancy on iron metabolism, plasma lactoferrin levels and granulocyte count in women]. / Der Einfluss hormoneller Kontrazeptiva und der Schwangerschaft auf Eisenstoffwechsel, Plasmalactoferrinkonzentration und Granulozytenzahl der Frau.

Plasma iron, total iron-binding capacity, transferrin, serum ferritin, plasma lactoferrin and the number of circulating granulocytes were determined in 51 healthy, non-iron-deficient women. Blood was sampled at three stages of the menstrual cycle of 6 women with spontaneous menstruation and of 6 on low-estrogen hormonal contraception. Furthermore, 39 pregnant women were studied at three stages in the second half of uncomplicated pregnancy (13 women per stage). Women on oral contraceptives differed from those with spontaneous menstrual cycles in that they did not show a drop of plasma iron at menstruation, and, on the average, they had slightly higher serum ferritin concentrations, lower plasma-lactoferrin levels and a decreased number of circulating granulocytes. No significant difference was found with respect to total iron-binding capacity and transferrin concentration. In pregnancy, a progressive increase of total iron-binding capacity and transferrin, and an intermittent decline of serum-ferritin, followed by a rise shortly before delivery, were observed. Plasma lactoferrin increased in parallel with the number of circulating granulocytes. An attempt is made to separate findings that have to be attributed to a direct hormonal effect on iron metabolism from those that may depend on other factors.

Blood coagulation and acute iron toxicity. Reversible iron-induced inactivation of serine proteases in vitro.

Coagulopathy is a hallmark of severe ferrous sulfate poisoning in humans and laboratory animals. Although nontransferrin-bound Fe3+ is thought to initiate the disorder, little is known about how it interferes with blood coagulation. At iron concentrations comparable to those of previous animal investigations, we reproduced the coagulopathy, in other words, the dose-related prolongation of the prothrombin, thrombin, and partial thromboplastin time, in human plasma in vitro. Studies of the mechanism by which iron prevents a normal plasma coagulation revealed that the proenzymes of the coagulation cascade and fibrinogen were not damaged by iron. Fibrinogen coagulability and fibrin monomer aggregation were unaffected by very high iron concentrations. Instead, thrombin was markedly inhibited by iron in its clotting effect on fibrinogen and, specifically, in its fibrinopeptide A-generating capacity, the inhibitory effect being reversible upon iron removal by EDTA chelation and gel filtration. Thrombin generation in the presence of iron was reduced as well, indicating an inhibition of one or several other enzymes of the intrinsic coagulation cascade. Because the amidolytic activity of human thrombin as well as factor Xa, kallikrein, and bovine trypsin was also reversibly suppressed by ferrous sulfate as well as ferric citrate, we consider it likely that the coagulopathy occurring in iron poisoning is the consequence of a general, physiologically important phenomenon: the susceptibility of serine proteases to nontransferrin-bound Fe3+.

Regulation of iron absorption and storage iron turnover.

The regulation of iron supply to plasma was studied in male rate. Repeated exchange transfusions were first carried out with plasma from iron-deficient or iron-loaded animals. There was no recognizable effect on the amount of iron entering the plasma as evidenced by plasma iron concentration or iron absorption by recipient animals. In other studies, iron compounds having different tissue distribution were injected. Subsequent iron release was greater from reticuloendothelial cells than from other iron-loaded tissues. When requirements for transferrin iron were increased by exchange transfusion with high reticulocyte blood, within minutes there was a doubling of the rate of tissue iron donation. It was concluded from these studies that (1) iron turnover in the plasma is primarily determined by the number of tissue receptors for iron, particularly those of the erythron, (2) that the amount of iron supplied by each donor tissue is dependent on the output of other donor tissues, and (3) that a humoral mechanism regulating iron exchange is unlikely in view of the speed of response and magnitude of changes in plasma iron turnover. It is proposed that there is some direct mechanism that determines the movement of iron from donor tissues to unsaturated transferrin binding sites.

[Lienal and intravascular corpuscular hemolysis in erythropoietic protoporphyria]. / Lienale und intravasale korpuskuläre Hämolyse bei erythropoietischer Protoporphyrie

A report is presented on two brothers with erythropoietic protoporphyria (EPP) with massively and moderately elevated RBC-protoporphyrin content respectively. Both exhibited splenic and one also intravascular hemolysis. The mechanism of hemolysis was investigated on the basis of filterability, plasma trapping and osmotic resistance of in vivo RBCs and of incubated, UV-light exposed RBCs. Photodynamic damage to EPP-RBC, leading to increased RBC rigidity, increased splenic trapping and intravascular hemolysis, appears to play a crucial role in the causation of hemolysis in vivo as well as in vitro.

A Swiss family with hemoglobin P Galveston beta117His leads to Arg, including two patients with hb P/beta thalassemia.

The mutant Hb P Galveston (beta117His leads to Arg) is observed in two heterozygotes for beta thalassemia and by itself does not cause clinical symptoms. Some of the physico-chemical properties of Hb P Galveston are identical to the onemical properties of Hb P Galveston are identical to the ones hemoglobin Zurich (beta 63 His leads to Arg) so that only a detailed analysis led to its proper identification.

Oxidative injury to erythrocytes, cell rigidity, and splenic hemolysis in hemodialyzed uremic patients.

In 23 hemodialyzed patients the metabolic defect of erythrocytes related to uremia and potentiated by dialysis was studied to establish a possible link with the shortened erythrocyte survival. A highly significant correlation was found between sulfhemoglobin provoked by oxidative stress and erythrocyte rigidity measured by filterability. Impaired filterability also correlated with the degree of splenic sequestration. Both sulfhemoglobin and impaired filterability correlated with the degree of hemolysis. Finally, erythrocyte survival showed a highly significant correlation with the degree of anemia. From osmotic fragility, plasma trapping, erythrocyte ATP and 2,3-diphosphoglycerate (DPG), and serum phosphorus, calcium, and magnesium measurements it seems unlikely that either spheric transformation or sol-gel transformation of the membrane is causing the increased erythrocyte rigidity. In view of the impaired erythrocyte defense capacity against oxidative injury, cell content rigidity as mediated by reduced hemoglobin solubility is a more likely explanation. Our results give a rational basis for a trial of splenectomy in severely anemia hemodialyzed patients.