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Biomedical subjects

F R Rickles

Publications and source records attributed to F R Rickles.

At least 91 records · Page 5Linked to original sources
PubMed1982

Familial chronic mononucleosis.

A syndrome of chronic mononucleosis occurred in two members of a family. Symptoms were chronic malaise and fatigue; recurrent upper respiratory tract infections; and mild, variable immune abnormalities. Intermittently positive heterophil titers were present for more than 2 years after acute infectious mononucleosis. Epstein-Barr-virus-specific antibodies were persistently abnormal. In the proband, the R component of the early antigen complex was present for 3 years and she never developed normal antibodies to Epstein-Barr nuclear antigen. Her brother had low to absent Epstein-Barr nuclear antigen titers, and antibodies to both the R and D component of the early antigen complex. Primary and acquired immunodeficiency states can show abnormal Epstein-Barr-virus-specific serologic findings that may reflect an attempt by the host to limit virus spread in the presence of deficient immune responses. This action may result in alterations of the Epstein-Barr virus-latent state, and lead to a chronic active infection and a syndrome of chronic mononucleosis.

Adult↗
PubMed1982

Mononuclear cell modulation of fibroblast procoagulant activity.

The release of procoagulant material by connective tissue cells as a sequel to cell injury can initiate blood coagulation and may thus play a role in he pathogenesis of inflammatory lesions. Human foreskin fibroblasts were shown to synthesize high levels of the procoagulant TF in vitro. Generation of TF by fibroblasts was inhibited by addition of supernatants of PHA-stimulated human mononuclear cells to fibroblast cultures. The inhibition was independent of supernatant effects on cellular proliferation and was accompanied by up to a 20-fold increases in PGE2 synthesis in the fibroblast cultures. The inhibition of TF generation by MC-SNs was reversed by adding indomethacin to the fibroblast cultures, suggesting that mononuclear cells suppress fibroblast TF generation by stimulation of endogenous fibroblast synthesis of prostaglandin. Regulation of fibroblast PCA by products of immune cells may be important in the pathogenesis of inflammatory lesions.

Cells, Cultured↗
PubMed1981

Coexistence of a primary immunodeficiency disorder and Hodgkin's disease: evidence against a B-lymphocyte origin for the Reed-Sternberg cell.

A 44-year-old woman with a life-long history of recurrent sinopulmonary infections developed Hodgkin's disease with characteristic Reed-Sternberg cells in a biopsy specimen of a mediastinal lymph node. Hypogammaglobulinemia was documented on several serum determinations and plasma cells were absent from biopsy specimens of the lymph node and bone marrow. Immunochemical studies failed to demonstrate any B lymphocytes bearing surface immunoglobulin or Fc-receptors for IgG in the peripheral blood. Pokeweed mitogen stimulation of the patient's peripheral blood lymphocytes in vitro resulted in the development of virtually no plasma cells. Peripheral blood T-lymphocyte number and function were defective initially. Following chemotherapy and radiotherapy, peripheral blood E-rossette-forming cells returned to normal, but T-cell function remained defective and B lymphocytes remained undetectable. These findings are compatible with the presence of two separate immune disorders: a primary hypogammaglobulinemia and Hodgkin's disease. The absence of lymphocytes bearing surface Ig or Fc-receptors for IgG in this patient adds further support against a B-lymphocyte origin for the Reed-Sternberg cell.

Adult↗
PubMed1981

Effect of warfarin on survival in small cell carcinoma of the lung. Veterans Administration Study No. 75.

In a controlled, randomized study, survival of patients with small cell carcinoma of the lung (SCCL) was prolonged on addition of warfarin sodium to combination chemotherapy plus radiation therapy. Median survival for 25 control patients was 24 weeks and for 25 warfarin-treated patients was 50 weeks. This difference could not be accounted for by differences between groups in performance status, extent of disease, age, or sex. The survival advantage associated with warfarin administration was observed both for patients with extensive disease and for those who failed to achieve complete or partial remission. The warfarin-treated group also demonstrated a significantly increased time to first evidence of disease progression. These results suggest that warfarin may be useful in the treatment of SCCL and also support the hypothesis that the blood coagulation mechanism may be involved in the growth and spread of cancer in man.

Antineoplastic Agents↗
PubMed1981

Fibrinopeptide A in acute leukemia: relationship of activation of blood coagulation to disease activity.

Plasma fibrinopeptide A (FPA) levels were determined in 20 unselected adult patients with acute nonlymphocytic and lymphocytic leukemia. The mean FPA level in patients with active disease (15.0 ng/ml) was significantly higher than during clinical remission (2.4 ng/ml, p less than 0.01). Elevated FPA levels were observed in patients with all morphological forms of acute leukemia. In the group of patients in clinical remission, 20/47 FPA values remained elevated beyond the normal range, suggesting that low-grade intravascular coagulation was present even when no leukemic cells were observed. Sequential studies revealed reduction of FPA levels to the normal range in five patients who entered clinical remission after chemotherapy and rapid elevation of the levels in eight patients who entered relapse after clinical remission. FPA levels rose significantly in five patients studied during induction chemotherapy. Thus, subclinical activation of blood coagulation, as defined by elevation of plasma FPA level, may occur commonly in acute leukemia. Plasma FPA generation may relate to leukemic disease activity.

Acute Disease↗
PubMed1981

Abnormalities of blood coagulation in patients with cancer. Mononuclear cell tissue factor generation.

Activation of blood coagulation, as characterized by the occurrence of disseminated intravascular coagulation, increased levels of plasma FPA, and the local deposition of fibrin, is common in both experimental animals and patients with malignant tumors. Many mechanisms have been proposed for the mediation of this response to tumors, including tumor-associated proteases, platelet adherence to tumors, surface activation of blood coagulation by tumor cells, and activation of coagulation by tissue factor derived from either tumor tissue or reactive leukocytes. We have investigated the hypothesis that MTF generation may contribute to increased fibrin generation in cancer patients. Plasma FPA levels and in vitro unstimulated MTF generation were measured simultaneously in samples obtained from 35 patients with lung cancer. FPA levels were significantly elevated in these patients as compared to a group of 20 normal volunteers (p = 0.03). Although unstimulated MTF generation showed considerable variability in both the patients and the normal volunteers, a high degree of correlation was observed between simultaneous levels of FPA and MTF regardless of whether MTF was expressed per cell (r = 0.83), per monocyte (r = 0.95), or per volume of peripheral blood (r = 0.96). MTF generation was also significantly decreased in a group of patients receiving sodium warfarin (p less than 0.001). These results suggest a potential role for MTF generation in the activation of blood coagulation in neoplasia and also suggest the possibility that inhibition of MTF generation by warfarin may be partially responsible for the decreased FPA values previously reported in anticoagulated cancer patients.

Aged↗
PubMed1980

Recurrent acute hepatitis following the use of factor VIII concentrates.

During a 3-yr period, a patient with hemophilia A experienced 5 episodes of acute hepatitis within 7-16 days following 5 separate infusions of factor VIII (FVIII) concentrates. Although the exact mechanism of the recurrent hepatitis remains unclear, these episodes most likely represented repeated allergic reactions to an antigenic protein derived from the FVIII concentrates. Although no evidence was found for a specific humoral immune response to FVIII in the circulation of the patient, an isolated cellular immune response was suggested by the finding of in vitro lymphocyte stimulation in response to the FVIII concentrate. This unusual type of posttransfusion hepatitis must be added to the list of adverse responses to FVIII concentrates.

Acute Disease↗
PubMed1980

The role of human T cells (and T cell products) for monocyte tissue factor generation.

Monocytes generate the procoagulant material tissue factor (TF) when mixed mononuclear cell cultures are stimulated with antigens, mitogens, or bacterial endotoxin in vitro. Optimal monocyte TF production has been shown to require the presence of lymphocytes in the culture system. We have investigated the nature of this lymphocyte requirement by stimulating monocytes grown in the presence of varying numbers of T lymphocytes. In addition, some monocytes were grown in the presence of conditioned media prepared from T lymphocyte cultures. The results of these studies have demonstrated two pathways for monocyte TF generation: a relatively T cell-independent pathway that can be stimulated by endotoxin or PPD and a highly T cell-dependent pathway that can be stimulated by PHA. In addition, the lymphocyte requirement for PHA-induced monocyte TF generation may be replaced by conditioned media from T cell cultures.

Cell Adhesion↗
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

Polycythemia vera and mesenteric arterial thrombosis. A disease association resulting from decreased platelet sensitivity to aspirin.

Recurrent mesenteric arterial thrombosis developed in a 56-year-old man with polycythemia vera (PV) despite therapy with heparin sodium, warfarin sodium, and standard doses of aspirin and dipyridamole. Platelet aggregation studies disclosed a normal response to aggregating agents in the presence of blood levels of aspirin that usually inhibit in vitro platelet aggregation. Increasing the in vivo dose of aspirin was associated with inhibition of in vitro platelet aggregation and, thereafter, arterial thrombosis did not recur. This case demonstrates that some patients with PV and arterial thrombosis may be refractory to standard doses of anticoagulants and platelet antiaggregating agents.

Aspirin↗
PubMed1979

Mononuclear cell tissue factor: cell of origin and requirements for activation.

Human mononuclear leukocytes generate the procoagulant material tissue factor (TF) following stimulation by endotoxin, mitogens, or antigens in vitro. We have examined tissue-factor generation by mononuclear cell subpopulations prepared in a variety of ways in order to determine the cell of origin of mononuclear cell TF and the conditions necessary for maximal in vitro TF generation. We have also examined the relationship between in vitro TF generation and in vivo or in vitro measures of delayed hypersensitivity in response to identical antigen stimulation. Our results demonstrate that the monocyte is responsible for the bulk of mononuclear cell TF generation in vitro and that adhesion alone is not sufficient stimulation for significant.

Cell Adhesion↗
PubMed1978

Delayed hypersensitivity in man: effects of systemic anticoagulation.

Skin test reactivity, lymphocyte transformation, and mononuclear cell tissue factor generation were evaluated both before and during systemic anticoagulation in 24 volunteers. Anticoagulation with warfarin decreased skin test induration and tissue factor generation, but lymphocyte trnasformation remained unchanged. An intact coagulation mechanism, including tissue factor generation, appears to be important for the development of skin test induration in humans.

Adult↗