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Biomedical subjects

W B Forman

Publications and source records attributed to W B Forman.

At least 19 recordsLinked to original sources
PubMed1992

Influence of age, performance status, body weight, and tumor type in individuals with cancer on the disposition of warfarin and its enantiomers: Department of Veterans Affairs cooperative study number 75.

Plasma warfarin and its R,S enantiomer concentrations, one-stage prothrombin times, and mean daily warfarin doses were analyzed in 196 patients given warfarin. These individuals were part of a controlled clinical trial that examined the effect of warfarin as an adjuvant to "standard" treatment in a variety of malignancies. Neither the plasma warfarin concentration nor the daily warfarin dose required to produce a given degree of prothrombin-time prolongation was influenced by age or body weight in these subjects. When the data were analyzed by performance status, we noted several variations of interest. Individuals with different tumor types demonstrated disparities in warfarin disposition. Patients with colorectal cancer, for example, required lower mean daily warfarin doses to achieve a given degree of one-stage prothrombin time prolongation. Analysis of warfarin enantiomers (R,S) in a selected group of patients demonstrated a lower-than-normal ratio (2:1) for the colorectal cancer group (1.42:1) because of an apparent decrease in the plasma R component. In contrast, patients with head and neck cancer demonstrated a ratio of 2.85:1, and the R component was elevated. Warfarin disposition and the effect of warfarin on vitamin K-dependent clotting factor production were altered in the patients with cancer reported in this study. The mechanisms for these alterations are complex and not completely understood.

Aging↗
PubMed1991

Current approaches to chronic pain in older patients.

As the population ages, primary care physicians face an increasing number of individuals who suffer from the effects of chronic diseases, including the accompanying chronic pain. This article reviews the common causes of pain in the elderly and suggests a system for assessing its severity. Five different approaches to treating pain in this population are outlined, as are guidelines for managing the potential side effects of treatment.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Effect of mopidamol on survival in carcinoma of the lung and colon: final report of Veterans Administration Cooperative Study No. 188.

Mopidamol (RA-233), a derivative of dipyridamole, is a phosphodiesterase inhibitor that has been shown previously to limit progression of malignancy in certain experimental animal models and in a pilot study in humans. RA-233 plus chemotherapy was compared with chemotherapy alone in a 5-year double-blind trial involving 719 patients with advanced carcinomas of the lung and of the colon. RA-233 treatment was associated with a statistically significant prolongation of survival in patients with non-small cell lung cancer (N-SCLC) limited to one hemithorax and with reduction in mean plasma fibrogen concentration. RA-233 was not toxic. The favorable effects on survival could not be explained by any factor other than the RA-233 treatment. In other tumor categories tested, no differences in survival were observed. These results suggest that RA-233 is useful in the treatment of N-SCLC of limited extent. They also suggest that therapeutic intervention aimed at modified intracellular pathways might constitute a novel investigative approach to the treatment of cancer.

Carcinoma↗
PubMed1987

Abnormalities of blood coagulation tests in patients with cancer.

Routine blood coagulation tests were performed on 431 consecutive patients enrolled in a study of the role of anticoagulation in cancer treatment (VA Cooperative Study #75). Two hundred sixteen control patients were treated with standard therapy, and 215 patients were treated with standard therapy plus sodium warfarin. At the time of entry into the study, the most common abnormalities were elevated fibrinogen levels, platelet counts, and fibrinopeptide A levels. Serial studies demonstrated a steady increase in platelet count and fibrinogen levels before death. Anticoagulation lowered FPA levels but had no significant effect on fibrinogen levels, platelet counts, or euglobulin clot lysis times. An unexpected finding was a dramatic increase in fibrin split product levels after institution of anticoagulation (means +/- SEM = 42.6 +/- 116.4 vs. 2.9 +/- 7.0 mg/L in control subjects; P less than 0.02). This study supports the presence of subclinical activation of blood coagulation in most patients with cancer. Moreover, the preferential activation of fibrinolysis in anticoagulated patients suggests a role for a vitamin K-dependent factor(s) in the regulation of fibrinolysis in patients with cancer.

Blood Coagulation Tests↗
PubMed1986

Consolidation and maintenance therapy in multiple myeloma: randomized comparison of a new approach to therapy after initial response to treatment.

A randomized, controlled trial was initiated in 1977 to evaluate the impact of three alternative approaches to consolidation and maintenance therapy after initial maximal response for multiple myeloma. All patients were treated initially with BCNU, cyclophosphamide, and prednisone (BCP) until a designated level of response was achieved. Responders were randomly assigned to either melphalan and prednisone (MP); prednisone, Adriamycin (Adria Laboratories, Columbus, Ohio), azathioprine, and vincristine (PAIV), or no therapy until relapse, then treatment with BCP. Initial response rates were comparable with previous trials. A small number of incremental responses were observed with both MP and PAIV. Survival was the same for all three maintenance approaches and the same as that observed in our previous continuous BCP or MP therapy. Additional or consolidation/maintenance therapy of the type administered here appears to offer little advantage once an initial response has been achieved.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Bleeding complications from warfarin anticoagulation in patients with malignancy.

Bleeding complications from warfarin anticoagulants were analyzed in 431 patients with carcinoma of the lung, colon, prostate and head and neck who were admitted to a randomized, controlled therapeutic trial of this agent. A total of 215 patients were randomized to the warfarin-treated group and 216 to the control groups. The mean prothrombin time was significantly prolonged (p = 0.0001) for warfarin-treated patients. The duration of warfarin administration was 64.9% of the total followup period providing 101 patient-years of experience with warfarin in cancer. Both the overall incidence of bleeding episodes (58% of warfarin-treated versus 30% of control) and the incidence of major bleeding episodes (42% versus 14%, respectively) were significantly increased in the warfarin-treated group (p = less than 0.001). The incidence of major bleeding was 1.86 per patient-year on warfarin. The most common sites of bleeding (in descending order) were the gastointestinal tract, the urinary tract, the nasal passages and skin. Hemorrhage occurred in association with the terminal event in 10 warfarin-treated and 12 control patients. Warfarin anticoagulation may have contributed to terminal bleeding in 3 (1.4%) patients. There was no difference in mean hemoglobin or hematocrit values for patients with versus patients without bleeding episodes.

Clinical Trials as Topic↗
PubMed1979

Rationale and experimental design for the VA Cooperative Study of Anticoagulation (Warfarin) in the Treatment of Cancer.

Anticoagulants have been demonstrated to reduce tumor growth in certain experimental animal systems. Inhibition of clot formation interferes with tumor growth and spread while enhancement of coagulation promotes tumor growth and spread. The fact that the coagulation mechanism is commonly activated in human malignancy together with preliminary reports of therapeutic efficacy of anticoagulants suggests that the coagulation mechanism may be of pathophysiologic significance also in the growth of human tumors. A VA Cooperative Study has been established to test the hypothesis that warfarin anticoagulation will modify the course of malignancy in man. The purpose of this paper is to present the rationale and experimental design for this study with emphasis on management of anticoagulant administration in cancer patients. This paper serves as the basis for forthcoming reports of toxicity and therapeutic efficacy of warfarin in human malignancy.

Animals↗
PubMed1979

Cancer in persons with inherited blood coagulation disorders.

In order to assess the influence of an inherited blood coagulation disorder in individuals who developed cancer, a mail survey of physicians who care for individuals with a bleeding diathesis was evaluated. Sixty-one individuals in an estimated population of 10,500 with both disorders were identified. An apparent increase in the incidence of cancer in the genitourinary and musculoskeletal systems was noted. However, in the largest group ( hemophilia) the primary site of cancer was similar to an age and sex matched population. There did not appear to be a change in the onset of metastatic disease in these individuals, as compared to an individual with cancer who did not have an inherited blood coagulation disorder.

Adolescent↗
PubMed1978

Fibrin formation: effect of calcium ions.

Using laser fluctuation spectroscopy, a technique that measures particle size change in solution, the kinetics of fibrin clot formation from fibrinogen can be studied. With this technique the effect of calcium on the three distinguishable phases of clot formation, (1) proteolysis of fibrinogen, (2) fibrinogen-fibrin monomer complex formation, and (3) fibrin monomer polymerization, were investigated. Only a small change in the length of the induction period that results from the fibrinogen-fibrin monomer interactions was observed. However, there was a marked increase in the rate of fibrin monomer polymerization in the presence of calcium ions. These data show that calcium decreases the time required for fibrin formation from fibrinogen by markedly accelerating the phase of fibrin monomer polymerization.

Blood Coagulation↗
PubMed1977

Nonsynthetizing multiple myeloma.

A case of multiple myeloma with no monoclonal protein synthesis is reported. The patient had hypogammaglobulinemia, bone marrow invasion, osteolytic lesions, and plasma cell tumors. The absence of protein synthesis has been demonstrated in bone marrow culture with tritiated leucine. No evidence of immunoglobulin production was found. Bone marrow or plasma cell tumor biopsy may be the only method of diagnosis in such cases.

Bence Jones Protein↗
PubMed1977

Techniques for demonstration of the specificity of circulating anticoagulants against antihemophilic factor (factor VIII), with studies of two cases possibly related to diphenylhydantoin therapy.

Circulating anticoagulants against antihemophilic factor (AHF, factor VIII) sometimes seem to inactivate other clotting factors as well. Measurements of the concentration of clotting factors in highly diluted plasma, or after neutralization of the anticoagulant with purified AHF, have demonstrated the specific nature of the anticoagulant in a patient under treatment with diphenylhydantoin. A second case in a patient treated with this agent, and with penicillin, an agent previously associated with the evolution of circulating anticoagulants, is also described.

Adult↗
PubMed1976

Fibrin formation: the role of the fibrinogen-fibrin monomer complex.

The process of fibrin formation using highly purified fibrinogen and thrombin was studied using laser fluctuation spectroscopy, a method that rapidly determines particle size in a solution. Two periods in fibrin clot formation were noted: an induction period during which no fibrin polymerization occurred and a period of rapid increase in particle size. Direct measurement of fibrin monomer polymerization and fibrinopeptide release showed no evidence of an induction period. These observations were best explained by a kinetic model for fibrin clot formation incorporating a reversible fibrinogen-fibrin monomer complex. In this model, the complex serves as a buffer system during the earliest phase of fibrin formation. This prevents the accumulation of free polymerizable fibrin monomer until an appreciable amount of fibrinogen has reacted with thrombin, at which point the fibrin monomer level rises rapidly and polymerization proceeds. Clinically, the complex may be a homeostatic mechanism preventing pathological clotting during periods of elevated fibrinogen.

Animals↗
PubMed1976

Criteria for the differentiation of dysfibrinogenemic states.

A large number of families have now been described in whom affected individuals have within their plasmas an abnormal species of fibrinogen (factor I). These defects, presumably examples of the phenomenon of allotypy--i.e., the synthesis of variant forms of a normal protein--have been inherited as autosomal dominant characteristics. In the great majority of cases, clotting is abnormally slow when thrombin is added to the abnormal plasma. Sometimes this defect appears to reside in impaired release of fibrinopeptides by thrombin. In other cases, fibrinopeptide release proceeds normally, but aggregation of fibrin monomers is impeded. In the latter instance, aggregation may be abnormally slow or, once it begins, it may proceed at a normal rate. Curiously, a bleeding tendency is more likely to occur in patients in whom fibrinopeptide release is impaired, while dehiscence of operative wounds rarely complicates dysfibrinogenemias associated with impaired aggregation of fibrin monomers; thrombosis has been described in both groups of patients. Most of the reported cases may be distinguished by functional criteria and by the physicochemical behavior and biochemical nature of the abnormal protein. Additonally, one family has been described in which plasma clots abnormally rapidly upon addition of thrombin, and two others in which crosslinking of fibrin by fibrin-stabilizing factor (factor XIII) is defective.

Afibrinogenemia↗
PubMed1973

Studies on the nature of antihemophilic factor (factor VIII). Further evidence relating the AHF-like antigens in normal and hemophilic plasmas.

Normal human antihemophilic factor (AHF, factor VIII) and the protein antigenically related to it in hemophilic plasma both appeared in the void volume of columns of agarose (Sepharose 4B) during purification of these agents. On ultracentrifugation upon sucrose gradients, both agents had sedimentation characteristics similar to those of an S30 marker. After reduction, the polypeptide chains of purified normal AHF and of the nonfunctional agent from hemophilic patients had an apparent molecular weight of 200,000 as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. These observations suggest that AHF, purified as described, exists as a large molecule with subunits of molecular weight of approximately 200,000. Antisera to normal AHF and the nonfunctional agent from hemophilic plasma appeared to be directed against antigens of similar electrophoretic mobility and precipitating characteristics, present in normal and hemophilic plasma but deficient in severe von Willebrand's disease plasma. Both antisera neutralized the AHF clot-promoting activity present in normal plasma, and this property was removed by absorption of the antisera with concentrates of normal or hemophilic plasma but to a greatly reduced extent by concentrates of von Willebrand's disease plasma. These findings suggest that the antigen detected in normal plasma by the antisera appears on a molecule participating in the AHF clot-promoting reaction.

Animals↗