Pathogenetic key position of thromboangitis: the endothelial cell. Serum dependent proliferation studies of endothelial cells in obliterative angiopathies.
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Adult↗
Biomedical subjects
M Köhler
Publications and source records attributed to M Köhler.
[Successful treatment of superior mesenteric artery thrombosis with local high-dose urokinase therapy].
A 56 year old man presented with increasing abdominal pain. He suffered from arterial occlusive disease with occlusion of the right A. iliaca communis. Angiography revealed partial thrombotic occlusion of the superior mesenteric artery. Urokinase (UK) at a dose of 150 IU/kg X minutes and heparin (1,000 U/h) was infused through the 7F angiographic catheter for 180 minutes. After 70 min of treatment, angiography showed improvement, and after 120 min the thrombus was nearly completely lysed. A stenosis of approximately 50% was still present after 180 min. Two hours after treatment the patient was pain free without analgesics. Laboratory studies showed systemic fibrinogenolysis, but fibrinogen was still within the upper normal range. Only slight systemic fibrinolytic activity (less than 5 IU UK/ml) could be determined. However, alpha 2-antiplasmin was depleted. The catheter was drawn 15 h after thrombolysis without bleeding. While under concurrent heparin and phenprocoumon therapy, the patient developed an infected gluteal hematoma as a result of i.m. injections prior to this treatment. A repeat angiography approximately one month after thrombolysis revealed further improvement and patency. The patient is well and free of abdominal angina and under oral anticoagulant therapy.
Drug Therapy, Combination↗
[Transitory oligoclonal paraproteinemia with virus infection and malignant lymphatic disease].
Oligoclonal paraproteinaemia occurred in two patients with malignant lymphocytic disease (highly malignant non-Hodgkin lymphoma, B-cell type of acute lymphocytic leukaemia), in one case during a cytomegalovirus infection and in the other during an infectious mononucleosis. At that time both patients were in complete remission. Paraproteinaemia in the first case disappeared within a year where the transformation from an initially four-banded paraproteinaemia (2 IgM-lambda and 2 IgG-lambda) into a three-banded paraproteinaemia (IgG-lambda) could be observed. In the second patient the concentration of the paraprotein decreased considerably. Because both patients were no longer under cytostatic treatment after manifestation of the paraproteinaemia, and were in complete remission during the whole of the observation period (4 years and 1 year), a direct relationship with the primary disease is unlikely. The transitory paraproteinaemia appears to be rather the result of an acquired defect of the immune system.
Agammaglobulinemia↗
The use of heat-treated Factor VIII-concentrates in von Willebrand's disease.
In vitro investigations have demonstrated a high F VIII:Rcof potency and a high F VIII:Rcof/F VIII R:Ag ratio of two heat-treated F VIII concentrates. We therefore studied the in vivo effectiveness of these preparations (F VIII HSR, Behringwerke Marburg and F VIII HTR, Travenol) in five patients with von Willebrand's disease (vWd). In the steady state in vivo recoveries of F VIII:Rcof ranged from 73-153% after transfusion of F VIII HSR and from 11.5-17% after F VIII HTR respectively. The gain of F VIII-complex after F VIII HS was comparable to cryopecipitate (KryobulinR SP, Immuno AG Wien). All three products shortened the bleeding-time. Three of our five patients underwent surgery (Billroth I, papillotomy, laparatomy, open heart surgery) under F VIII HS cover without bleeding complications. The dose applied ranged from 20 to 40 U/kg at 8 or 12 h intervals for a period of approx. 14 days. Serum-transaminase elevations were observed in two of four patients after F VIII HT treatment. Although the risk of hepatitis of heat-treated F VIII concentrates remains to be determined, these products proved to be effective in vWd. The major advantages of these preparations are stability, rapid solubility, a low content of contaminating proteins, and a rapid, general availability.
Chemical and Drug Induced Liver Injury↗
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↗
Identification of mitochondria-rich cells in unstained vital preparations of epithelia by autofluorescence.
To recognize mitochondria-rich cells in unstained vital preparations of heterogeneously composed epithelia we report here the use of an autofluorescence technique. Upon illumination with wavelengths of 400-440 or 450-490 nm mitochondria-rich cells emit fluorescence light of wave-lengths of greater than 470 or greater than 520 nm respectively, which probably arises from flavoproteins. Illumination does not seem to impair cell function and the fluorescence does not show any sign of fading over observation times of 20 min or greater. The method allows us to identify parietal cells from chief cells in gastric glands and obviously also intercalated cells from principal cells in renal collecting ducts. It might also be useful in other epithelia.
Animals↗
Membrane potentials of individual cells of isolated gastric glands of rabbit.
Individual glands of rabbit gastric mucosa were prepared for measurements of cell membrane potentials. In the first experiments a collagenase isolation technique was used which produced gland fragments that were fixed on agarose. In later experiments a microdissection technique was used which allowed whole glands to be isolated that were held in suction pipettes. Individual parietal or chief cells could be recognized and impaled with microelectrodes, however, the yield of reliable recordings was small and the distinction from artifacts sometimes difficult. In acceptable recordings the membrane potentials of both cell types varied between around -20 and -35 mV or exceptionally -50 mV in both preparations, with mean values being around -26 mV. The significance of the recordings was tested by ion substitution experiments. Substitution of all chloride by sulfate increased the membrane potential to values ranging up to -60 and -80 mV that are commonly observed in other cells.
Animals↗
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↗
[Specificity and normality of peripheral systolic pressure measurement by the ultrasound Doppler technic in healthy angiography-imaged extremities].
Our investigations on 108 healthy extremities, whereby in all cases normality was angiographically proven, demonstrate that the ankle systolic pressure (156.9 +/- 23.8 mmHg) was significantly higher than the arm systolic pressure (140.6 +/- 21.7 mmHg). Blood pressure was not measured at the same time but consecutively. We used the CW-Doppler system. The specificity is 100% if the decided limit is placed at minus 5 mmHg, that is, the ankle systolic pressure lies 5 mmHg, below the arm systolic pressure. A sufficient discrimination is also-evident if the determined normality limit is defined as no difference in pressure or higher systolic pressure in the ankle than in the arm (specifity: 98.1%). With our method we have found differences in the left and right lower extremities in 43.2% of cases. The relation of peak systolic blood pressure of the arm to that of the ankle was not dependent on blood pressure nor age. Our investigation has shown that the diagnostic reliability of the Doppler ultrasonic technique is particularly high.
Adult↗
[Successful treatment of progressive dialysis encephalopathy. Case report].
A case of severe aluminium-induced dialysis dementia and osteopathy is described. Under DFO-therapy a complete remission could be achieved within 8 months.
Aluminum↗
[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 effect of 4 different antacids on the gastrointestinal tract and mineral metabolism].
In a double-blind, randomized study, six healthy women were given four different antacids containing aluminium, magnesium or calcium, for a period of seven days, respectively. The antacids investigated were Trigastril 50 Del, Maaloxan Suspension, Kompensan-S forte Suspension and Solugastril 50 Gel. All the antacids tested led to a significant increase in the stool frequency and accelerated stool transit time. The sodium-containing agent produced a significantly greater acceleration as compared with the other antacids. No changes in the sodium, potassium or calcium blood levels were seen prior to and after administration of the various antacids. All preparations reduced phosphate concentrations (significant only with Solugastril an Trigastril). In the case of Maaloxan with a high content of magnesium, the magnesium concentration was increased mildly, but significantly. Irrespective of the dose of aluminium employed, all the antacids resulted in a significant increase in aluminium concentration of between 23 and 36 micrograms/l. All the antacids significantly reduced the excretion of phosphate in the urine. The preparation with a high level of magnesium produced the greatest excretion of magnesium, the preparation containing calcium the greatest excretion of calcium, in 24-hour urine. The results show that the effects on the weight of the stools, the transit time, the consistency of the stools, and on the mineral balance, depends upon the composition of the respective antacid.
Aluminum↗
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↗
[Clinical evaluation of co-tetroxazine in acute purulent sinusitis and acute tonsillitis in a double-blind comparison].
127 outpatients, 78 with acute purulent sinusitis and 49 with acute tonsillitis, were treated for 7 days with a benzylpyrimidine -sulphonamide combination. In this double-blind and randomized study 59 patients received co- tetroxazine (100 mg tetroxoprim and 250 mg sulphadiazine) b.i.d., whilst the reference substance, co-trimoxazole (160 mg trimethoprim and 800 mg sulphamethoxazole) was given to the remaining 68 patients b.i.d. The test criteria were the therapeutic efficacy and both subjective and objective tolerance. An improvement in clinical symptoms and signs occurred in both conditions under each therapeutic regimen. Clinical therapeutic success was rated very good or good in 96.6% treated with co- tetroxazine and in 97.1% of patients treated with co-trimoxazole. In the former group therapy failed in 1 patient with sinusitis and in 1 with acute tonsillitis . In 98.3% of patients treated with co- tetroxazine the tolerance was very good or good, whilst the respective figure for co-trimoxazole was only 91.2%. 6 patients suffered from side effects ( gastric spasm, gastralgia , nausea, vomiting, diarrhoea) which were so severe in 2 cases that treatment had to be prematurely terminated. The generally good tolerance to both preparations was confirmed by the results of the laboratory investigations.
Acute Disease↗
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↗