PubMed Health⌕ Search

Biomedical subjects

W R Friedenberg

Publications and source records attributed to W R Friedenberg.

17 recordsLinked to original sources
PubMed1992

Relationship of thrombohemorrhagic complications to endothelial cell function in patients with chronic myeloproliferative disorders.

Thrombotic and hemorrhagic disorders are common complications of the myeloproliferative disorders. Endothelial cells release both procoagulant and profibrinolytic factors, which may contribute to these hemorrhagic or thrombotic complications. The pre- and postvenous stasis levels of the procoagulant and profibrinolytic factors produced by endothelial cells were correlated with the occurrence of complications in polycythemia rubra vera (PRV) patients (n = 29) and essential thrombocythemia (ET) patients (n = 17) compared with normal patients (n = 17). Tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor (PAI) activity, von Willebrand's factor (vWF) activity and antigen (vWF:Ag), and factor VIII activity were measured. The resting tPA activity was significantly higher in the two disease groups compared with normal controls, but no difference between the levels of tPA and either complication within the disease groups was observed. Significantly elevated tPA following venous stasis was observed in the patients of both disease groups who had bleeding complications. Significant decreases, compared with the normal group, in both resting and postvenous stasis levels of PAI were observed in the disease groups regardless of complication history. The subjects from both disease groups with thrombotic complications had significantly elevated resting vWF and both resting and postvenous stasis vWF:Ag levels compared with normal controls. The endothelial cell is likely to be responding to abnormal hemostasis rather than being primarily involved in the genesis of a hyper- or hypocoaguable state.

Adult↗
PubMed1992

Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial.

Thrombolysis of acute pulmonary embolism can be accomplished more rapidly and safely with 100 mg of recombinant human tissue-type plasminogen activator (rt-PA) (Activase) than with a conventional dose of urokinase (Abbokinase) given as a 4,400-U/kg bolus dose, followed by 4,400 U/kg per h for 24 h. To determine the effects of a more concentrated urokinase dose administered over a shorter time course, this trial enrolled 90 patients with baseline perfusion lung scans and angiographically documented pulmonary embolism. They were randomized to receive either 100 mg/2 h of rt-PA or a novel dosing regimen of urokinase: 3 million U/2 h with the initial 1 million U given as a bolus injection over 10 min. Both drugs were delivered through a peripheral vein. To assess efficacy after initiation of therapy, repeat pulmonary angiograms at 2 h were performed in 87 patients and then graded in a blinded manner by a panel of six investigators. Of the 42 patients allocated to rt-PA therapy, 79% showed angiographic improvement at 2 h, compared with 67% of the 45 patients randomized to urokinase therapy (95% confidence interval for the difference in these proportions [rt-PA minus urokinase] is -6.6% to 30.4%; p = 0.11). The mean change in perfusion lung scans between baseline and 24 h was similar for both treatments. Three patients (two treated with rt-PA and one with urokinase) had an intracranial hemorrhage, which was fatal in one. The results indicate that a 2-h regimen of rt-PA and a new dosing regimen of urokinase exhibit similar efficacy and safety for treatment of acute pulmonary embolism.

Acute Disease↗
PubMed1991

High-dose carmustine and autologous bone marrow reinfusion in the treatment of refractory or relapsed small cell lung carcinoma.

Fourteen patients with small cell carcinoma of the lung in relapse or with disease refractory to chemotherapy were treated with carmustine (BCNU) at doses of 600 to 1000 mg/m2 intravenously followed by autologous bone marrow transplantation. All patients previously were treated with cyclophosphamide, doxorubicin, vincristine, and etoposide. Seven of the 14 patients responded to the high-dose BCNU (50% response with 95% confidence limits ranging from 23% to 77%). Three patients had a complete response, and four had a partial response. Regrowth of tumor occurred within 60 days of treatment in the responding patients. Death occurred in six patients before the recovery of the platelet count to 50,000 cells/microliters. Although the response rate was high, the toxicity was excessive. In the dosage range of 600 to 1000 mg/m2 in heavily pretreated patients, BCNU is not recommended, but additional investigation may be warranted in patients with central nervous system metastases who previously were treated with radiation therapy.

Adult↗
PubMed1991

High-dose dexamethasone for refractory or relapsing multiple myeloma.

In order to assess the efficacy and toxicity of dexamethasone as a single agent without the concomitant infusion of Adriamycin and vincristine (VAD), an ECOG pilot study was initiated using 40 mg by mouth daily for 4 days every week for 8 weeks. Patients who responded were then maintained on the same treatment, but at 2 week intervals. Of the 32 patients evaluable for response, three were completely refractory to all prior therapy. All patients had advanced disease and 26 had received multiple prior treatments. There were 13/32 (40%) objective responses by ECOG criteria. Of the 28 patients evaluable for subjective response, i.e., significant decrease in performance status and/or bone pain, eight (28.5%) responded. Of the 34 patients evaluable for toxicity, 19 patients (55%) had moderate to severe side effects, including nine who had central nervous system effects, three who had gastrointestinal bleeding, two who had pulmonary emboli, one with psychosis, and four who had serious infections with one death. Median survival for the entire group was 19 weeks, with 31 weeks in the responders and 9 weeks in the non-responders. Although high-dose dexamethasone is capable of producing a significant number of partial responses (40%), it is associated with excessive toxicity. Less frequent administration of the dexamethasone at 2 week intervals was well tolerated in the maintenance of partial response, but has not been studied for efficacy in induction of remission.

Adolescent↗
PubMed1991

Treatment of advanced non-Hodgkin's lymphoma in adults.

Although dramatic progress has been made in the treatment of advanced non-Hodgkin's lymphoma, a majority of patients eventually die from this disease. Improvements in histopathology, staging techniques, immunophenotyping, and knowledge of prognostic factors have improved our ability to choose appropriate treatment. Most low-grade lymphomas can be effectively palliated for many years, but eventually convert to large-cell lymphomas or become resistant to chemotherapy. Intermediate-grade lymphomas, especially diffuse large-cell lymphomas, may be cured in 30% to 60% of the cases with aggressive combination chemotherapy. The high-grade lymphomas require treatment similar to regimens designed to treat acute lymphocytic leukemia, including central nervous system (CNS) prophylaxis. Non-Hodgkin's lymphomas are becoming more common in patients with acquired immunodeficiency syndrome (AIDS), and may be effectively controlled before the immunodeficiency becomes too severe. All patients with high-grade lymphoma and others at high risk should be tested for human immunodeficiency virus (HIV). Patients who relapse may be salvaged with chemotherapy, and their diseases are potentially curable with autologous or allogeneic bone marrow transplantation. New treatments using monoclonal antibodies, biological response modifiers, and growth factors, should improve palliation and survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Treatment of venous thromboembolic disease. A pragmatic approach to anticoagulation and thrombolysis.

Heparin (Lipo-Hepin, Liquaemin Sodium) and warfarin sodium (Coumadin, Panwarfin) are the classic anticoagulants in use for venous thromboembolic disease. They work by modifying the coagulation mechanism, heparin having an immediate effect and warfarin having a more delayed effect. The most common adverse effects of anticoagulation therapy are hemorrhagic complications. Thrombolytic therapy should be considered in all patients with massive pulmonary embolism with hypotension and in patients with deep venous thrombosis in the popliteal area or higher. Such therapy has been shown to help preserve the pulmonary microcirculation after pulmonary embolism and to decrease the incidence of the postthrombotic syndrome following deep venous thrombosis. If certain clinical guidelines are followed rigidly, the incidence of significant bleeding complications is low. Although the use of tissue plasminogen activator in venoocclusive disease has been limited to isolated cases, results have been very promising.

Drug Administration Schedule↗
PubMed1986

Improved survival in the treatment of advanced Hodgkin's disease at a nonuniversity institution (1970-1979).

From 1970 through 1979, 89 patients with Hodgkin's disease were treated at the Marshfield Clinic/St. Joseph's Hospital. After the pathologic material was reviewed, the patients were analyzed to compare Group I (1970-1973) with Group II (1974-1979). Demographic characteristics in the two groups were similar. In the decade, 76% of patients achieved complete remission. In advanced-stage disease, 50% of patients achieved complete remission in Group I compared with 68% in Group II. At 5 years, 50% of patients were alive without COPP (cyclophosphamide, vincristine, procarbazine, prednisone) chemotherapy; with this treatment, 75% of patients survived (P = 0.02). There was improved survival comparing Group I (56% at 5 years) with Group II (76% at 5 years) patients with advanced disease (P = 0.004). More aggressive combination chemotherapy (COPP) was related to the improvement in survival (P less than 0.001). The advances in treatment made by cooperative groups and universities are being transferred to nonuniversity institutions, with appropriate improvement in survival of Hodgkin's disease.

Adult↗
PubMed1986

Granulocyte dysfunction and myotonic dystrophy.

A 52-year-old Caucasian male with typical features of myotonic dystrophy (MD) developed a lung abscess and was found to have a mild atypical cyclic neutropenia. Granulocyte function testing revealed a defect in phagocytosis, bactericidal activity and chemotaxis. The defects were less severe at the nadir of the granulocyte counts. Skin windows demonstrated that the granulocyte defects were not just an in vitro artifact. The patient was treated with lithium carbonate and improved. Mobilization into a skin window and clinical MD were unchanged. Studies of his 10 children and 2 siblings, including granulocyte function tests and complete neurological evaluations were obtained. The 4 children with abnormal parameters of granulocyte function all had definite evidence of MD. Two children had equivocal findings of MD and the others were normal. There was minimal evidence of granulocyte dysfunction in these children. Twelve of 19 unrelated patients with MD had evidence of impaired granulocyte function with the most consistent defect being chemotaxis in response to bacterial factor. Mild granulocyte dysfunction is frequently associated with MD, but severe dysfunction with many defects is uncommon but can occur, as in this family. There was a tendency for the more severely afflicted members of this family to have more pronounced granulocyte dysfunction. Longitudinal testing in this family may determine any relationship between the granulocyte dysfunction and the onset of MD, as well as any correlation with the progression of the disorder. MD patients who develop infection should have granulocyte function tests as part of their evaluation.

Adolescent↗
PubMed1985

High-dose cytosine arabinoside-associated pancreatitis.

Thirty patients with leukemia and lymphoma have been treated at our institution with high doses of cytosine arabinoside (Ara-C). Gastrointestinal symptoms were frequent after therapy, and 6 of the 30 patients had severe abdominal pain. Of the six, two had pancreatitis; two had normal amylase and lipase determinations; and in two, neither amylase nor lipase levels were determined. The two patients with pancreatitis are presented because this complication of high-dose Ara-C therapy has not been described. The authors conclude that pancreatitis can follow high-dose Ara-C chemotherapy and that patients with abdominal pain following this treatment be evaluated for pancreatitis.

Adult↗
PubMed1985

Local intra-arterial streptokinase therapy for acute peripheral arterial occlusions. Should thrombolytic therapy replace embolectomy?

Locally administered low-dose streptokinase was used in 13 patients with acute arterial occlusions. Systemic fibrinolytic effects were noted in each of 11 patients in whom some effective thrombolysis was demonstrated. In the two patients with no angiographically demonstrable thrombolysis, a systemic lytic effect was absent. Bleeding complications were frequent (31%). Three patients required amputations and one patient died. The systemic lytic effects of streptokinase appear to be necessary for complete clot lysis. Locally administered streptokinase appears to have no significant benefit compared to high-dose systemic administration. Occlusions accessible to balloon embolectomy should probably be treated surgically, reserving fibrinolytic therapy for inaccessible lesions. More research is needed to clarify the specific indications, as well as to determine optimal methods of administration and dosage.

Acute Disease↗
PubMed1978

Platelet dysfunction associated with cardiopulmonary bypass.

The clinical significance and pathogenesis of the platelet dysfunction following cardiopulmonary bypass were studied in conjunction with the degree of functional impairment associated with the use of membrane and bubble oxygenators. Forty consecutive patients had the following tests preoperatively and postoperatively: complete blood count (CBC), platelet count, prothrombin consumption time, bleeding time, prothrombin time, partial thromboplastin time, fibrinogen, euglobulin clot lysis, fibrin degradation products, and platelet aggregation tests. Six patients were given 14C-serotonin tests before and after operation, and preoperative and postoperative electron micrographs were made of the platelets of 3 patients. The amount of blood lost, the blood transfused, and plasma hemoglobin levels were also measured. Abnormal aggregation of platelets was found, with no difference between the membrane and bubble oxygenators. In vitro aggregation tests with protamine sulfate and hemoglobin solutions, as well as the 14C-serotonin studies and electron micrographs, suggest that platelets acquire storage pool deficiency and an abnormal membrane during cardiopulmonary bypass.

Blood Coagulation Tests↗
PubMed1978

Atypical purpura fulminans with benign monoclonal gammopathy.

A 67-year-old woman with a history of thrombophlebitis had been taking warfarin sodium for 1 1/2 years when she developed multiple skin lesions resembling warfarin-induced skin necrosis or purpura fulminans. Despite discontinuing the warfarin and administering prednisone, the lesions increased in size. Disseminated intravascular coagulation (DIC) was found and resolved with heparin sodium therapy, and her skin lesions healed. This patient was believed to have an atypical form of purpura fulminans rather than warfarin-induced skin necrosis because of the duration of warfarin therapy and the dramatic resolution with heparin. A monoclonal (IgG) gammopathy was found, which stabilized as the skin lesions resolved, and fulfilled the criteria for a benign (asymptomatic) monoclonal gammopathy.

Aged↗
PubMedDate not supplied

Local versus regional procurement and distribution of granulocytes.

Granulocyte concentrates obtained by discontinuous flow centrifugation (DFC) and continuous flow centrifugation (CFC) were studied. The DFC granulocytes were obtained from a regional center and stored for 24 hours prior to transfusion. The CFC granulocytes were obtained locally and transfused within a few hours. Even at 24 hours, DFC granulocytes had significantly reduced bactericidal capacity, chemiluminescence, nitroblue tetrazolium reduction, chemotaxis and random mobility. Granulocyte kinetics utilizing DF32P and skin windows demonstrated the ability of DFC granulocytes to circulate and migrate into the tissues despite the in vitro abnormalities. Until effective storage techniques for granulocyte preservation became available, rapid transportation and processing from regional centers or local procurement of granulocytes is necessary to transfuse functional granulocytes.

Blood Bactericidal Activity↗