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Biomedical subjects

S Panzer

Publications and source records attributed to S Panzer.

At least 127 records · Page 7Linked to original sources
PubMed1988

IIB von Willebrand's disease: pathogenetic and therapeutic studies.

Infusion of 1-deamino-(8-D-arginine)-vasopressin (DDAVP) into patients with IIB von Willebrand's disease (vWD) has been reported to induce thrombocytopenia. In some families with this disorder thrombocytopenia is present even in the resting state. We have investigated the basis of this chronic thrombocytopenia in one such patient by performing platelet recovery and survival studies. Increased platelet consumption was suggested by a decrease in platelet recovery (40.5%, normal 45%) and mean platelet survival (112 h, normal range 144-224 h). In addition, we have administered test infusions of DDAVP and observed the effect on bleeding time and platelet count. DDAVP caused a decrease in the median platelet count from 86 x 10(9)/l (range 30-221) to 60 x 10(9)/l (range 5-144), the individual decline in the nine subjects ranging from 12% to 84% compared to the pretreatment values. Formation of platelet aggregates was observed in all patients following DDAVP. The bleeding time was prolonged before DDAVP in all patients and lengthened further in two after the infusion. However, partial correction of the bleeding time was seen in three and normalization in one patient following DDAVP infusion. Two IIB vWD patients were treated with virus-inactivated cryoprecipitate (Ristofact). Infusion of cryoprecipitate was followed by rapid appearance of all but the largest vWF multimers in plasma and did not affect the platelet count. The bleeding time was normalized in one patient but remained prolonged in the other. In conclusion, in IIB vWD patients virus-inactivated cryoprecipitate is the treatment of choice in the case of bleeding. Infusion of DDAVP might be effective in a subset of IIB vWD patients that has yet to be characterized.

Bleeding Time↗
PubMed1988

The promoter for a sporulation gene in the spoIVC locus of Bacillus subtilis and its use in studies of temporal and spatial control of gene expression.

We have identified the transcription start site and regulatory region governing the expression of a sporulation gene in the spoIVC locus of Bacillus subtilis. Efficient expression and developmental regulation of this gene was controlled from a promoter region that extended no more than 110 base pairs upstream and no more than 4 base pairs downstream from the start site of transcription, on which basis we infer that spoIVC is regulated at the level of transcription initiation. Using a transcriptional fusion of the spoIVC gene to the lacZ gene of Escherichia coli, we found that spoIVC expression was turned on at the third to fourth hour of sporulation (at about the developmental stage [IV] that its products are required in spore formation) and that this transcription was largely restricted to the mother cell chamber of the sporangium. Mutations in many different spo genes (causing blocks at stages 0 to V) were found to influence (negatively and positively) the level of spoIVC expression. Our results distinguish the mode of spoIVC regulation from that of previously studied sporulation genes and indicate that it is representative of a new regulon of mother cell-specific gene expression.

Bacillus subtilis↗
PubMed1988

Decreased serum osteocalcin levels in phenprocoumon-treated patients.

Osteocalcin (OC) is a noncollagenous bone matrix protein containing gamma-carboxyglutamic acid, the synthesis of which is vitamin K dependent. Serum OC levels are generally believed to reflect the de novo synthesis of OC by osteoblasts and thus reflect bone formation. We measured serum OC levels by RIA in 48 patients receiving phenprocoumon anticoagulant treatment, which inhibits the posttranscriptional synthesis of gamma-carboxyglutamic acid, and in 22 matched normal subjects. The median serum OC level in the patients receiving phenprocoumon therapy was significantly lower than that in the normal subjects (P less than 0.0001). In 27 patients receiving anticoagulant therapy and in 21 normal subjects the proportion of noncarboxylated OC to total OC also was determined. The proportion of OC that was noncarboxylated was significantly higher in the patients receiving phenprocoumon therapy than in the normal subjects (P less than 0.0001). We conclude that OC carboxylation is impaired in patients receiving oral anticoagulant therapy. The decreased total OC levels in patients receiving phenprocoumon treatment might result from decreased bone formation, although these patients do not have symptoms of bone disease.

4-Hydroxycoumarins↗
PubMed1987

[Pathophysiology of autoimmune thrombocytopenia].

Current knowledge of the pathomechanism of autoimmune thrombocytopenias is discussed on the basis of our own experimental and clinical experience. Of particular interest is the role of the target antigen(s) involved. Autoantibody binding to certain antigens may result either in premature sequestration or in functional impairment of platelets, or in both. The mechanisms by which autoantibodies are formed are still poorly understood. Serological methods have increased our knowledge of the pathomechanisms of immune thrombocytopenias and studies with 111Indium labelled platelets provided detailed information on platelet kinetics. The importance of the reticuloendothelial system and the therapeutic consequences derived from experimental and clinical observations are discussed.

Autoantibodies↗
PubMed1987

[Allogeneic bone marrow transplantation in acute myeloid leukemia (AML): results in 14 patients].

Between February 1982 and August 1986 14 patients with AML (median age 24 years, range 10-41) underwent allogeneic bone marrow transplantation. 9 patients were grafted in first complete remission, 4 in first relapse, 1 in second relapse and 1 patient with refractory AML. Conditioning consisted of cyclophosphamide (120 mg/kg) and total body irradiation (1000 rad). The patients received methotrexate (n = 12) or methotrexate and cyclosporine (n = 2) for prevention of graft versus host disease. Of the 14 patients, 7 are alive, 7 patients died. Causes of death were recurrence of leukaemia (n = 2), veno occlusive disease of the liver (n = 1), CMV-pneumonitis (n = 1), septicaemia (1), cerebral haemorrhage (1), acute graft versus host disease of the gut (1), necrotizing encephalopathy (n = 1). 7 patients are alive between 124 and 1784 days (median 671) in continuous complete remission. All patients but 1 have a Karnofsky-index of more than 80%.

Adolescent↗
PubMed1987

[Bone marrow transplantation in chronic myeloid leukemia--experiences in 16 patients].

Between January 1983 and December 1986 16 patients (8 f, 8 m, median age 31.5 years, 14-41) with chronic myelocytic leukaemia (CML) received bone marrow grafts from their HLA compatible sibling donors. 11 patients were in the chronic and 4 in the accelerated phase. 1 patient was in lymphatic blast crisis. The patients were pretreated with busulfan (n = 15, total dose: 100-1000 mg, median: 225), mitobromitol (1 pat.), hydroxyurea (2 pats.), pre-irradiation of the spleen with 800 rad (1 pat.) and one patient had received 3 cycles of vincristin and prednisolone. The conditioning regimen consisted of cyclophosphamide (120 mg/kg) and total body irradiation (1000 rad, lung 800 rad). The prophylaxis against graft versus host disease (GVH-D) consisted of methotrexate (MTX) in 14 patients and of MTX in combination with cyclosporin-A in 2. At present (January 15th 1987) 9 patients survive 30 to 1210 days (median 1009) post graft (6/11 grafted in chronic, 2 of 4 in accelerated phase and 1/1 grafted in blast crisis. The causes of death were interstitial pneumonitis (CMV-associated, 2 pats.), venoocclusive disease of the liver (2 pats.), acute GVH-D and septicemia (2 pat.) and relapse (1 pat.). The Karnovsky score of 8/9 survivors is 100%, one patient has a score of 70% due to chronic GVH-D. Bone marrow transplantation for CML bears a high risk of early mortality but offers the unique option of permanent eradication of leukaemic haemopoiesis with subsequent long term survival.

Adolescent↗
PubMed1987

[Oral anticoagulant therapy--renaissance of an old therapy?].

Although the antithrombotic potential of oral anticoagulants is undisputed, bleeding complications constitute a serious problem. One of the main causes for these complications has been a lack of standardization of the prothrombin time. The introduction of the International Normalized Ratio (INR) has led to a better standardization of prothrombin time. Thus, the same level of anticoagulation can be reached using different reagents and therefore over- and undercoagulation can be avoided. Furthermore, the benefit/risk ratio can be improved by adapting the intensity of anticoagulation to the indication. The following clinical conditions are established indications for treatment with oral anticoagulants: Prevention of cardiac emboli in acute anterior myocardial infarction with atrial thrombus, in patients with atrial fibrillation with or without mitral valve disease, in patients with prosthetic heart valves and in patients with dilated cardiomyopathy. Furthermore, oral anticoagulants should be given to patients after femoropopliteal bypass. A relatively mild oral anticoagulant treatment (INR 2-3) is sufficient to prevent recurrences of venous thrombosis and pulmonary emboli. The duration of treatment in patients with venous thromboembolism depends on some clinical features and the results of clotting tests which indicate an increased tendency to thrombosis.

Administration, Oral↗
PubMed1987

[Right heart failure as a clinical sign of pulmonary artery sarcoma].

A 43 year-old female patient was admitted on account of severe dyspnoea of several months' duration and thrombocytopenia. The clinical symptomatology was compatible with pulmonary embolism, but no source of embolization was found and heparin therapy did not lead to clinical improvement. Angiography of the pulmonary artery revealed multiple filling defects. Symptoms improved after treatment with cortisone and so a malignant process was assumed. The patient died from right ventricular failure before the diagnosis could be established. At autopsy a sarcoma of the pulmonary artery, obviously originating from the pulmonary trunk was found. Thrombocytopenia most probably resulted from consumption of platelets by a mechanism corresponding to the Kasabach-Merritt syndrome. The difficulties in the diagnosis of pulmonary artery sarcomas are discussed and the 69 previously published cases are reviewed.

Adult↗
PubMed1987

Haemolytic transfusion reactions due to HLA antibodies. A prospective study combining red-cell serology with investigations of chromium-51-labelled red-cell kinetics.

In a prospective study to see whether HLA sensitisation is associated with increased red-blood-cell (RBC) destruction after HLA-incompatible transfusion, chromium-51-labelled RBC survival and site of sequestration were monitored in nine patients in whom HLA antibodies had developed after RBC transfusions. The donors selected were compatible in ABO and RBC-specific antigen systems but mismatched for the HLA antigen in question. Haemolytic transfusion reactions occurred in all four patients who received HLA-B7-incompatible RBC. A direct radioimmune anti-IgG test became positive, Cr51-RBC survival was very short (22.3, 36.9, 41.4, and 44.0 days), and excess sequestration in the spleen was measured. There was a rise in serum lactic dehydrogenase and a fall in haptoglobin. HLA-B7 antibody was detected in the eluate prepared from RBC collected after transfusion. A similar reaction was found in only one further patient, caused by an HLA-A2 incompatibility. No indications of immune-mediated RBC sequestration were discernible after transfusion of HLA-B7-compatible RBC in one of the patients who had shown a reaction with HLA-B7-incompatible blood, nor in any of the other patients who received HLA-B7-compatible RBC. The haemolytic transfusion reactions could not be anticipated by conventional crossmatch procedures, nor by the measurement of the Cr51-RBC survival 1 h after transfusion.

Aged↗
PubMed1987

Pedigree of the major histocompatibility complex in a family with a neonatal alloimmune thrombocytopenia.

Immunization of a mother negative for the platelet-specific antigen P1A1 against the P1A1 antigen of her child induced neonatal alloimmune thrombocytopenia. This prompt immune response occurred in her first pregnancy and we were therefore interested to study whether there is an association with genes located within the major histocompatibility complex. We deduced haplotypes of HLA-A, B, C and DR as well as of complement C2, C4 and Bf in the maternal family members.

Adult↗
PubMed1987

[Thrombocyte transfusion: increase in platelets in relation to clinical and immunologic prerequisites].

We determined in 35 patients with severe thrombocytopenia (AML n = 10; ALL n = 4; CML = 1; idiopathic myelofibrosis n = 1, aplastic anemia n = 1; undergoing bone-marrow transplantation n = 17) factors influencing the corrected count increment (CCI) after platelet transfusions. Out of 195 transfusions 86 (44%) failed to increased platelet counts (CCI less than 5 X 10(9) platelets/l). A significant percentage of transfusion failures occurred in patients with splenomegaly and/or fever (54% vs. 29%; p less than 0.002). Antibodies directed against donor platelets were found only twice. No correlation between reactivities demonstrable by the lymphocytotoxic test (n = 144) or the radioimmune antiglobulin test (n = 67) and the CCI was obvious. HLA antigen identity was also not predictive. Thus, transfusion failures in patients with low alloimmunization will not be predicted by in vitro antibody screenings. The patients' clinical condition has the most important influence on posttransfusion increment.

Anemia, Aplastic↗
PubMed1987

Stimulation of human pancreatic polypeptide and gastrin by Boots and GIH secretin: in vitro and in vivo studies.

We have studied the concentration of various gastrointestinal peptides in a crude porcine secretin (Boots) preparation and pure natural porcine secretin (GIH, Kabi) preparation. Boots secretin was found to contain 140.3 ng secretin, 1.27 ng human pancreatic polypeptide (hPP), 1.03 ng gastrin, 137.4 ng cholecystokinin (CCK), 241 microU insulin, 1.86 ng vasoactive intestinal polypeptide (VIP), 2.22 ng glucagon and 6.60 ng somatostatin (SRIF) per Crick Harper unit Boots secretin. Sephadex gel filtration demonstrated that the immunoreactivity was due to the hormone per se. GIH secretin contained 240 ng secretin per clinical unit (CU) and less than detectable concentrations of hPP, gastrin, CCK, insulin, VIP, glucagon and SRIF. To determine the clinical significance of having contaminating peptides in Boots secretin, we investigated the effect(s) in 4 subjects. Determined in a highly gastrin-specific assay, the mean plasma gastrin response to Boots secretin administration was slightly, but not significantly greater than the GIH secretin response at 1 and 2.5 minutes. However, in some subjects false positive elevations in plasma gastrin immunoreactivity occurred when some commercially available kit gastrin assays were employed. After intravenous injection of Boots secretin, mean plasma hPP levels rose significantly more than after GIH secretin administration. The mean peak plasma insulin level after GIH secretin administration was significantly higher than after Boots secretin. Neither secretin preparation caused a change in plasma glucose, glucagon and SRIF levels. From these results, it is suggested that GIH secretin be used as the preparation of choice in provocative testing for diagnosing gastrinoma or deficiencies of exocrine pancreatic function.

Adult↗
PubMed1986

Indium 111-labeled platelet kinetic studies and platelet-associated IgG in hairy cell leukemia.

In order to study the pathogenesis of thrombocytopenia in patients with hairy cell leukemia (HCL), levels of platelet-associated IgG (PAIgG), platelet life span (MLS), and the sequestration site of autologous 111In-labeled platelets were measured in nine patients with HCL. Splenectomized patients (n = 4) had a higher platelet count (x = 122.5 X 10(9)/l; range, 80-190 X 10(9)/l) as well as higher levels of PAIgG (x = 10.7%; range, 5.8-16.9%), than nonsplenectomized patients (platelets x = 76 X 10(9)/l, range 40-100 X 10(9)/l; PAIgG x = 3.2%, range 2.2-4.2%). A normal recovery of 111In-labeled platelets was found in splenectomized patients, whereas a very low recovery was observed in the nonsplenectomized group (x = 70.2%, range, 50-82.5%, versus x = 22.4%, range, 15-28.2%). The MLS was borderline normal in all patients. The site of sequestration was the spleen in nonsplenectomized patients. The low recovery of 111In-labeled platelets in nonsplenectomized patients suggests "hypersplenism" with pooling as a major cause of thrombocytopenia, in addition to impaired thrombocytopoiesis and possible immune-mediated platelet destruction.

Adult↗
PubMed1986

Platelet-associated immunoglobulins IgG, IgM, IgA and complement C3 in immune and nonimmune thrombocytopenic disorders.

A two-stage radioactive antiglobulin test--using unlabelled antisera specific for IgG, IgA, IgM and C3 followed by binding of 125I-staphylococcal protein A--was applied to determine platelet-associated immunoglobulins (PAIg) and complement (PAC3) in thrombocytopenias of various etiologies. One hundred and one patients with immune thrombocytopenia (chronic autoimmune, 48; acute autoimmune, 37; Evans syndrome, nine; connective tissue diseases, seven) and 20 patients with presumed nonimmune thrombocytopenia (bone marrow aplasia or malignancy, six; septicemia, five; hypersplenism, five; cirrhosis of liver, three; others, one) were studied. Increased levels of PAIg/C3 were found in 76% of patients with immune thrombocytopenia. PAIgG was raised in 66%, PAIgM in 57%, PAIgA in 44%, and PAC3 in 29%. Isolated elevation of PAIgG and of PAIgM was found in four and three cases, respectively; PAIgA and PAC3 were elevated in one case each. PAIgG was associated with PAIgM in 56%, with PAIgA in 34%, and with PAC3 in 27%. Both patients with Evans' syndrome and patients with connective tissue diseases had significantly higher PAIgM levels than the other patients with immune thrombocytopenia. In patients with nonimmune thrombocytopenia, increased rates of PAIg/C3 were also encountered. Positive test results were found in 88% (PAIgG 88%, PAIgM 47%, PAIgA 35%, and PAC3 24%). In immune-mediated thrombocytopenia, we observed a significant inverse correlation between platelet counts and PAIgG, PAIgA, and PAC3, but not with PAIgM. In contrast, no such correlation was found in patients with nonimmune thrombocytopenia. Our data indicate that the evaluation of neither parameter alone nor the combination of PAIg/C3 will discriminate between immune and nonimmune thrombocytopenia. Preferential coating with certain immunoglobulins, however, may be present in some subgroups of immune thrombocytopenias.

Blood Platelets↗
PubMed1986

Toxicity of sequential high-dose ARA-C asparaginase treatment in childhood poor risk leukemia.

Seventeen children and two adolescents, aged 6 months to 20 9/12 years, with poor risk leukemia were treated with a total of 38 sequential high-dose ARA-C-Asparaginase courses (HIDAC-ASNase). Each course was followed by profound myelosuppression. Fever occurred in 13.2% and infectious complications in 7.9% of courses. Other side effects were vomiting (81.6%), drug fever (55.3%), mucositis and diarrhoea (28.9%), mild hepatotoxicity (26.3%), exanthemas (18.4%), conjunctivitis (15.8%), local ASNase hypersensitivity (7.9%), athropathy (5.3%). One patient developed generalized seizures followed by coma and death. The possible association between ARA-C, the CNS symptoms and death could neither be demonstrated nor excluded. Except for the possible ARA-C related CNS toxicity, toxic effects were reversible. We consider this treatment a tolerable chemotherapeutic contribution in childhood.

Adolescent↗
PubMed1986

Efficacy of rhesus antibodies (Anti-Rh0 (D)) in autoimmune thrombocytopenia: correlation with response to high dose IgG and the degree of haemolysis.

We have compared the efficacy of high-dose IgG with that of Rhesus antibodies (anti-Rh0 (D)) in 5 patients with autoimmune thrombocytopenic purpura (3 adults and 2 children). Although only transient, high-dose IgG (0.4 g/kg X 5 days) was effective in all patients (peak values 50-200 X 10(9)/1), whereas anti-Rh0 (D) (11-20 micrograms/kg X 5 days) led to comparable results in only 3 patients (165 X 10(9)/1, 72 X 10(9)/1, 33 X 10(9)/1). This response to anti-Rh0 (D) was neither related to the degree of induced haemolysis (increase of LDH and decrease of haptoglobin) nor to the amount of IgG antibodies bound to red blood cells, as quantified by the 125-I-antiglobulin test. A decrease of platelet-associated IgG was recorded in 3 patients: 2 of them showed an improvement of platelet counts and in one of them there was no response. We conclude that the therapeutic response of high-dose IgG and anti-Rh0 (D) is independent of the degree of induced haemolysis and may not be predicted from the effectiveness of either therapy alone.

Adolescent↗