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Biomedical subjects

P Hellstern

Publications and source records attributed to P Hellstern.

At least 73 records · Page 4Linked to original sources

Prevalence of antibodies to human T-lymphotropic virus-III (HTLV-III) in hemophiliacs and other patients chronically substituted with blood products.

The prevalence of antibodies to human T-lymphotropic virus III (HTLV-III) was determined in a total of 140 hemophiliacs and 36 polytransfused patients from three medical centers by an enzyme linked immunosorbent assay (ELISA) and confirmatory tests. 58 hemophiliacs (41.4%) were seropositive. In all instances where the origin of the coagulation factors given to these patients could be determined, blood products came from the United States. In addition, 2 of 36 polytransfused patients, mostly with acute leukemias, who were transfused with blood products from local donors were positive for HTLV-III antibodies. No HTLV-III antibodies were detected in 237 blood donors selected in part from the donor pool of the polytransfused patients.

Antibodies, Viral↗

Gray platelet syndrome: selective alpha-granule deficiency and thrombocytopenia due to increased platelet turnover.

Clinical and laboratory studies of two siblings, both suffering from gray platelet syndrome (GPS) are described. The patients had a mild bleeding disorder, their platelets were blue-gray in panoptic stains, and alpha-granules were markedly reduced, as shown by electron microscopy. The platelet content of platelet factor 4 and that of beta-thromboglobulin were significantly reduced (3%-7% of normal). Platelet count was decreased (33-150 X 10(9)/1) and small platelets were increased in platelet volume distribution. Bleeding time was prolonged on most occasions. Bone marrow aspiration was performed in one patient and revealed increased reticulin fibers, however, megakaryocyte count was normal. The mean platelet survival was 4.8 days using 111indium-labelled platelets. In this patient, platelet-associated IgG was within the normal range. Prednisone therapy failed to increase platelet count. Dental surgery was performed under cover of desmopressin and no bleeding complication occurred; however, no improvement of bleeding time was observed. The patient delivered a healthy male infant without hemorrhaging while under concurrent platelet transfusion therapy.

Adult↗

Combined dys-form of homozygous factor XI deficiency and heterozygous factor XII deficiency.

A 12-year-old girl with lifelong hemorrhagic episodes was found to have both a dys-form of homozygous factor XI deficiency and heterozygous factor XII deficiency. The heredity of the coagulation defects was confirmed by family studies. Severe bleeding after dental surgery occurred in spite of replacement therapy and local measures including fibrin glue. Our findings suggest that the risk of bleeding in patients with homozygous factor XI deficiency must not be underestimated and that the most effective measure is the transfusion of sufficient amounts of fresh frozen plasma until at least the 5th postoperative day.

Blood Transfusion↗

Prevalence of antibodies to HTLV-III in AIDS risk groups in West Germany.

The prevalence of antibodies to human T-lymphotropic virus III was determined in acquired immunodeficiency syndrome (AIDS) risk groups by an enzyme linked immunosorbent assay and confirmatory tests in four different areas in West Germany. Twenty-four of 28 homosexual AIDS patients (86%), 24 of 33 homosexual patients with lymphadenopathy syndrome or AIDS related complex (73%), and 44 of 113 asymptomatic homosexuals at risk for AIDS (39%) were seropositive. In three groups of hemophiliacs, 8 of 35 in 1983 (23%), 25 of 65 in early 1984 (39%), and 19 of 23 in late 1984 (83%) showed positive results. Two sera from 36 polytransfused patients were also positive, whereas 36 selected blood donors, and 32 healthy laboratory and clinical personnel were all negative. Also no human T-lymphotropic virus III antibodies were detected in sera of 187 prostitutes in the Munich area.

Acquired Immunodeficiency Syndrome↗

[Treatment of von Willebrand-Jürgens syndrome with "hepatitis-free" factor VIII concentrates].

In five patients with von Willebrand's disease the haemostatic effect of heat-treated factor VIII concentrates was examined. For comparison, small-pool cryoprecipitate was used. All three preparations (Factor VIII-HT Hyland, Factor VIII HS Behringwerke, Kryobulin SP) were shown to improve abnormal laboratory findings, especially bleeding time, and at times even normalize them. It was possible to prevent bleedings during operative procedures, and effectively treat spontaneous bleedings. Factor VIII-HT and Factor VIII HS could be used in dosages comparable to cryoprecipitate (20-40 U/kg); in patients undergoing surgery a dose interval of eight hours is recommended. Two of four patients suffering of chronic liver disease had raised transaminase activities after receiving Factor VIII-HT. Although the risk of hepatitis cannot be conclusively assessed, the preparations used provide, owing to their good blood-clotting effect, an advance in the treatment and prevention of serious complications in patients with von Willebrand's disease.

Adult↗

The subcutaneous administration of the vasopressin analogue 1-desamino-8-D-arginine vasopressin in patients with von Willebrand's disease and hemophilia.

Twenty-one patients suffering from mild von Willebrand's disease (vWd) and patients suffering from mild or moderate hemophilia A received 1-desamino-8-D-arginine vasopressin (DDAVP) (Minirin, Ferring AG) s.c. at a dose of 0.4 microgram/kg body weight. Additionally, two hemophiliacs and 22 patients with vWd received DDAVP i.v. Within the observation period of 3 h Factor (F) VIII:C levels increased 2.4 X baseline levels in hemophiliacs, and the maximal effect was observed 3 h post DDAVP s.c. In patients with vWd post DDAVP s.c. (i.v.) a 2.7 (3.4), 2.1 (1.9) and 2.2 (2.8) fold increase for F VIII: C, F VIIIR:Ag and F VIII:Rcof was observed. In eight patients suffering from vWd with additional F XII deficiency a small and transitory but significant increase of F XII levels was detected post DDAVP s.c. No local or systemic side effects were observed. In five patients with vWd tooth extractions were performed without bleeding complications under DDAVP s.c. treatment. Two patients practiced self-treatment by injecting the drug s.c. at home. We thus conclude that s.c. DDAVP is an effective, reliable, and cost-reducing form of treatment that does not bring with it the risk of transmitting infectious diseases in patients with vWd and hemophilia and that can be administered at home.

Arginine Vasopressin↗

[Relevance of antithrombin III in thrombogenesis: the diagnosis and therapy of antithrombin III defects].

Pathological and inconspicuous AT III measuring values were compared with the clinical findings (arterial occlusive diseases, postthrombotic syndromes, acute profound thrombosis of the pelvic veins and the leg veins, acute heparin tolerance in several basic diseases). After calculatory elaboration of all rightly positive and falsely positive, rightly negative and falsely negative laboratory results becomes evident that the positive power of prognosis of the AT III determination is unsatisfactory for a certain basic disease and the negative evidence in these questionings rather well satisfy for the functional measuring method. - The sensitivity of the functional AT III test for the recognition of increased heparin tolerances is quite satisfactory, and the test for the answer of this questioning also suitable and more sensitive than the immunological proof method. - The high percentage of rightly positive and rightly negative findings of all tested results of apparently healthy persons and the groups of patients represented makes clear, which role plays the AT III as a physiologic inhibitor against coagulation-active serine proteases particularly in DIC and in profound thrombosis of the pelvic and leg veins. - For the observation of the course in profound thrombosis of the pelvic and led veins, features of postthrombotic condition and the DIC at least the functional determination of AT III is decisively important.

Antithrombin III↗

In vitro characterization of commercial Factor VIII concentrates: long-term follow-up.

Fifty batches of Factor VIII concentrates from 12 producers were characterized in a long-term follow-up. The following parameters were measured: Factor VIII: C, Factor VIIIR: AG, Factor VIII: Rcof, specific activity (U Factor VIII: C/mg protein), fibrinogen, IgG, IgM, IgA, isoagglutinins, Hbs-AG, heparin-like activity, thrombin-like activity, antithrombin III, Factor VIII-stability at room temperature, and the rate of complete dissolution of the lyophilizate. In most preparations there was an unacceptable batch-to-batch variation of both Factor VIII complex and contaminating proteins, which exceeded the inter-assay coefficient of variation of the applied test systems. Nevertheless, different brands could be recognized by their typical protein pattern. The results obtained suggest that the standardization of Factor VIII concentrates of unknown composition is still accompanied by considerable risks.

Drug Stability↗

[Significance of disordered antithrombin III function in disseminated intravascular coagulation and deep venous thrombosis for anticoagulant therapy].

In patients with acute deep vein thrombosis of the pelvis and limbs and in patients with decompensating course of DICFS considerable defects in AT III function are regularly demonstrated by laboratory tests, while in groups including patients with old or less pronounced venous thrombosis or in patients with compensated or overcompensated consumption coagulopathy normal AT III values might frequently be expected. This seems to be of interest for the interpretation of laboratory data on AT III. However, from these findings AT III replacement cannot be deduced and they cannot be used as a criterion to assess the prognostic value of AT III deficiency for the course of the underlying disease. In acquired AT III defects the anticoagulant activity of heparin is not necessarily decreased. After continuous infusion of doses below 500 USP in patients with DICFS and after administration of heparin doses of 750 USP/h/70 kg in patients undergoing fibrinolytic therapy the AT III content rather increases continuously. After extremely high heparin doses during extracorporeal circulation in the heart-lung machine transitorily decreased AT III values return to normal. In certain risk situations, however, such as after bolus injection of comparatively high heparin doses in patients with greatly reduced AT III values, a lowered anticoagulant effect of high heparin doses must be expected. In these cases AT III replacement is indicated. However, when enhanced heparin resistance is suspected or diagnosed, treatment with AT III concentrates is justified only when the diagnosis is based on laboratory findings. Cortisone and protamine chloride were found to exert direct effects on AT III function and concentration independent of the AT III defects mentioned.

Antithrombin III↗

Determination of factor XIII activity and of factor XIII inhibitors using an ammonium-sensitive electrode.

An assay for rapid factor XIII activity measurement has been developed based on the determination of the ammonium released during fibrin stabilization. Factor XIII was activated by thrombin and calcium. Ammonium was measured by an ammonium-sensitive electrode. It was demonstrated that the assay procedure yields accurate and precise results and that factor XIII-catalyzed fibrin stabilization can be measured kinetically. The amount of ammonium released during the first 90 min of fibrin stabilization was found to be 7.8 +/- 0.5 moles per mole fibrinogen, which is in agreement with the findings of other authors. In 15 normal subjects and in 15 patients suffering from diseases with suspected factor XIII deficiency there was a satisfactory correlation between the results obtained by the "ammonium-release-method', Bohn's method, and the immunological assay (r1 = 0.65; r2 = 0.70; p less than 0.01). In 3 of 5 patients with paraproteinemias the values of factor XIII activity determined by the ammonium-release-method were markedly lower than those estimated by the other methods. It could be shown that inhibitor mechanisms were responsible for these discrepancies.

Ammonium Chloride↗

Arterial and venous thrombosis and normal response to streptokinase treatment in a young patient with severe Hageman factor deficiency.

The case history of a patient with severe factor XII deficiency (factor XII activity and concentration below 1%) is described. The case reported gives further evidence that factor XII deficiency leads to a prolonged euglobulin lysis time. This might be a risk factor indicating a proneness to thromboembolic events. The young man suffered from arterial and venous thrombosis, and underwent lower extremity amputation without bleeding complications, as well as thrombolytic therapy to save the other leg. There was a normal response to streptokinase, heparin, and phenprocoumon treatment.

Adult↗

Thrombin-induced platelet malondialdehyde (MDA) formation in normal subjects and in women taking oral contraceptives.

Thrombin-induced platelet malondialdehyde (MDA) production and platelet count were studied in 82 male and 74 female healthy blood donors. 37 women on oral contraceptives (OC) had significantly lower values of MDA production than women who were not using the pill. There were no statistically significant differences of MDA production in women on a low dose estrogen, a medium dose, and a relatively high dose. Males had significantly higher values than females. In 15 further subjects (5 males, 5 OC-users, 5 OC-nonusers) the kinetics of MDA formation was determined by using increasing doses of thrombin. No significant differences could be found. Platelet count in women on OCs was lightly increased, but the difference was not significant.

Blood Platelets↗

Thyroid iodine concentration and total thyroid iodine in normal subjects and in endemic goitre subjects.

Thyroid iodine concentration and total thyroid iodine were determined by an automated technique by means of the ceric arsenious acid reaction in 42 males and 13 females. The thyroids were taken from autopsy material in a region with a low dietary intake. The accuracy of the method to estimate iodine was checked by neutron activation analysis. There was an excellent correlation between the iodine contents of thyroid specimens, when measured by chemical or by activation analysis. The mean iodine concentration was 1.86 mg/g dry weight and was found to be lower than in non-goitrous regions. In goitres, the mean iodine concentration was significantly lower, and the mean total thyroid of normal weight. There was no significant difference in iodine concentration and total iodine between males and females. The thyroid iodine concentration did not depend upon age in adults. The data were log normally distributed. It was established that mean iodine concentrations under 2 mg/g dry weight or 0.45 mg/g fresh weight are to be regarded as an important index of iodine deficiency.

Aged↗

The influence of citrate concentration on the quality of plasma obtained by automated plasmapheresis: a prospective study.

BACKGROUND: There is a need for more comprehensive work dealing with the quality of plasma collected by automated plasmapheresis using different final concentrations of citrate anticoagulant. A prospective study was performed to examine the influence of three concentrations of sodium citrate on the levels of clotting factors and markers of activated hemostasis and fibrinolysis. STUDY DESIGN AND METHODS: Fifty-one experienced plasma donors were recruited for subsequent 750-mL plasmapheresis procedures using 4-percent (wt/vol) sodium citrate. Anticoagulant-to-blood ratios of 1:16.6, 1:14.2, and 1:12.5 were used, corresponding to sodium citrate concentrations of 6 percent, 7 percent, and 8 percent (vol/vol), respectively. Between two plasmapheresis procedures, there was a washout period of 7 days. Determinations were made of the plasma levels of fibrinogen and factors V, VII, VIII, and IX, as well as antithrombin, tissue-type plasminogen activator, and several markers of activated hemostasis and fibrinolysis: activated factor VII, prothrombin splits products, D-dimers, and beta-thromboglobulin. RESULTS: The plasma samples anticoagulated with 6-percent citrate contained significantly higher levels of factors V, VIII, and IX than the samples anticoagulated with 8-percent citrate (p<0.0001, p< or =0.0001 and p = 0.009, respectively). The citrate concentration had no influence on the levels of fibrinogen, factor VII, antithrombin, or tissue-type plasminogen activator. There was no evidence that the plasma samples containing lower citrate concentrations were more prone to activation of hemostasis or fibrinolysis. CONCLUSION: A reduction in the final citrate concentration of plasma collected by automated plasmapheresis results in higher yields of factors V, VIII, and IX without activation of hemostasis. More comprehensive studies should confirm previous work dealing with the establishment of the lowest citrate concentration acceptable in plasma used as therapeutic fresh-frozen plasma or as starting material for the manufacture of plasma derivatives.

Adult↗

[In vitro studies on the effect of dissolved and undissolved heterologous collagen sponge on human thrombocytes].

Hemostasis in bone-bleeding is difficult. Local haemostatics are often used. We take xenolog collagen-sponge--in bone defects--combined with synthetic apatite, to achieve additional osteoinduction. Mechanism of haemostasis by collagen-sponge is examined. After a detailed discussion of literature in vitro experiments with xenolog collagen-sponge and dissolved collagen-sponge (Pentapharm Braun Melsungen) are reported. While native collagen is an important natural haemostatic agent, this collagen-specific effect is not observed in our experiments, neither in platelets nor in endoplasmatic haemostasis. Regarding clinical eperiences physical effects must be considered as mechanism of haemostasis by xenolog collagen-sponge.

Blood Platelets↗