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Biomedical subjects

T Yamakami

Publications and source records attributed to T Yamakami.

15 recordsLinked to original sources

Alteration of coagulation and fibrinolysis systems after multidrug anticancer therapy for lung cancer.

Recently, an increased frequency of thromboembolic events has been reported after the administration of anticancer drugs. The precise mechanism by which these vascular phenomena occur is unknown. The current work aims at evaluating the alterations of the coagulation and the fibrinolysis systems during the administration of antineoplastic agents by means of newly developed markers of haemostasis. This investigation comprised 25 lung cancer patients treated with multidrug combination chemotherapy. D-dimer, plasmin-alpha 2-antiplasmin complex, fibrin degradation products, fibrinogen, antithrombin III, thrombin-antithrombin III complex, prothrombin time and activated partial thromboplastin time were measured from samples taken before and on days 2, 5, 7, 14 and 21 after the administration of antineoplastic drugs. A significant reduction in plasma concentration of fibrinolytic activity markers, DD and PAP, was observed on days 5 and 7, and on days 2, 5, 7 and 14, respectively, following the administration of chemotherapeutic drugs. Statistically significant shortening of PT and APTT on days 2, 5, 7 and 14, as well as significant elevation of the thrombin generation marker TAT were observed on days 5 and 7 after chemotherapy. These results show that relatively higher levels of coagulation activation and a lower fibrinolytic activity occur during cytotoxic drug therapy compared with basal values. Small variations of haemostatic values and a short follow-up period may explain why no thrombotic events were observed during this study. Although further studies must be done to clarify these findings, the results of this investigation suggest that an imbalance of the coagulation-fibrinolysis system might be a contributing factor in the pathogenesis of thrombotic complications during chemotherapy.

Adult

Correlation between clotting and collagen metabolism markers in rheumatoid arthritis.

Rheumatoid arthritis is a chronic inflammatory disease caused essentially by an immune-mediated mechanism. However, abnormalities of the clotting system have also been incriminated as having an important role in the pathogenesis of this disease. This study aims at assessing the clotting system and collagen metabolism alterations and the relationship between perturbances of the hemostatic pathway and the destructive and fibroproliferative processes in patients with rheumatoid arthritis. The coagulation system was evaluated by measuring thrombin-antithrombin III complex (TAT), prothrombin time (PT), activated partial thromboplastin time (APTT), and antithrombin III (AT-III). The fibrinolysis system was assessed by measuring fibrin degradation products (FDP), fibrinogen (FBG), alpha 2-antiplasmin (alpha 2-PI), D-dimer (DD) and plasmin-alpha 2-antiplasmin complex (PAP). As markers of collagen metabolism, the type III procollagen peptide (PIIIP) and the 7S domain of type IV collagen (7S-collagen) were determined. Blood concentrations of DD, PAP, TAT, PIIIP, and 7S-collagen were significantly higher in rheumatoid arthritis patients compared to controls. Serum levels of PIIIP were significantly correlated with PT, APTT, AT-III, FDP, and DD. 7S-collagen levels were inversely related to AT-III and FBG values. This study demonstrated the occurrence of a subclinical intravascular coagulation in rheumatoid arthritis and suggested the important role of blood coagulation in the alteration of the extracellular matrix metabolism in this disease.

Adult

Correlation between increased granulocyte elastase release and activation of blood coagulation in patients with lung cancer.

BACKGROUND: Coagulopathies often are associated with malignant tumors. The pathogenesis of these complications in cancer is not clear. Host inflammatory (monocyte/macrophage) cell-mediated triggering of clotting activation has been suggested. METHODS: The objective of this study was to evaluate the role of neutrophil-derived elastase in the activation of blood coagulation and fibrinolysis in lung cancer. The study population was 42 consecutive patients with lung cancer (34 men and 8 women). Thirteen patients had small cell lung cancer (SCLC), 13 had squamous cell lung cancer, and 16 had adenocarcinoma. Hemostatic function was assessed by measuring D-dimer (DD), thrombin-antithrombin III complex (TAT), plasmin-alpha 2-antiplasmin complex (PAP), fibrin degradation product (FDP), fibrinogen, prothrombin time (PT) and activated partial thromboplastin time (APTT). Elastase-alpha 1-protease inhibitor (EPI) complex was measured as a marker of neutrophil activation. RESULTS: Significant elevation of the elastase plasma levels and coagulation-fibrinolysis parameters was found in patients with cancer compared with control subjects. Among all patients, the plasma concentration of EPI was significantly correlated with APTT, DD, TAT, PAP, and fibrinogen. Although in patients with non-small cell lung cancer (non-SCLC), DD, TAT, PAP, APTT, and fibrinogen were significantly correlated with EPI, such a correlation was not found in patients with SCLC. Patients with non-SCLC had stronger correlation of EPI with TAT, PAP, and PT than did patients with advanced stages of disease. CONCLUSION: The activation of coagulation-fibrinolysis system in lung cancer may be triggered, at least in part, by an increased release of neutrophil elastase. This mechanism is stage related and seems to operate predominantly in non-SCLC.

Adenocarcinoma

Evaluating prethrombotic state in lung cancer using molecular markers.

Clotting abnormalities are well-recognized complications that occur with high frequency in patients suffering from underlying malignant diseases. New and highly sensitive molecular markers of hemostasis, thrombin-antithrombin III complex (TAT III), D-dimer fragments (DD), and plasmin-alpha 2-antiplasmin complex (PIC) were measured in 58 consecutive lung cancer patients. Significant elevation in the blood concentrations of DD, PIC, and TAT was found in lung cancer patients, with either extensive or limited disease compared with values obtained in a healthy control group and in another group of patients with chronic obstructive pulmonary disease. Patients with distant metastasis exhibited significantly higher levels of these parameters as compared to those without metastasis. These data indicated that there was a subclinical activation of blood coagulation and fibrinolysis in lung cancer from the early clinical stages of the disease. In addition, there appeared to be different levels of clotting activation according to histologic type of tumor and response to chemotherapy.

Adenocarcinoma

Coagulation-fibrinolysis system and markers of collagen metabolism in lung cancer.

BACKGROUND: Evidence suggests that the fibrinolysis system and peritumoral connective tissue play important roles in tumor spread. METHODS: In this study, the authors evaluated the following parameters in 30 consecutive patients with lung cancer: thrombin-antithrombin complex (TAT), cross-linked fibrin split products D-dimer (DD), plasmin-alpha 2-antiplasmin inhibitor complex (PAP), and two antigens related to connective tissue, the aminoterminal propeptide of type III procollagen (PIIIP) and the 7S domain of type IV collagen (7S-collagen). RESULTS: Each parameter was increased significantly in the patients with cancer compared with the control subjects. Except for PIIIP, their concentration in blood was elevated to a significantly greater extent in the patients with distant metastases. The PAP concentration correlated well with the plasma concentration of TAT (r = 0.5; P < 0.01) and DD (r = 0.9; P < 0.0001). There was also a strong correlation between the serum concentrations of PIIIP and 7S-collagen (r = 0.7; P < 0.001). In patients with localized disease, DD levels were correlated significantly with those of PIIIP (Spearman rank-order correlation [rs] = 0.6; P < 0.025) and 7S-collagen (rs = 0.6; P < 0.01). In the group with disseminated metastases, there was a significant inverse relationship between serum PAP concentrations and serum concentrations of 7S-collagen (rs = -0.6; P < 0.025). CONCLUSIONS: These results confirm the presence of a subclinical chronic activation of the parameters of intravascular clotting-fibrinolysis and alterations in the extracellular matrix of patients with lung cancer. These parameters may be useful as indicators of the clinical progression of malignant disease, particularly of lung cancer.

Adult

Bronchopulmonary disease in ulcerative colitis.

Two cases of ulcerative colitis are described: a 33-year-old woman who developed widespread bronchiectasis 7 months after undergoing colectomy, and a 72-year-old man whose colonic disease began coincidentally with the appearance of diffuse interstitial pulmonary infiltrates. In both cases, clinical correlation and common patterns of response of lung and bowel diseases suggested that the co-existence of these two pathologies might not be merely a casual relation.

Adult

[Pharmacokinetic study and side effects of chronic daily administration of oral etoposide].

Eleven inoperable patients with non-small cell lung cancer were treated as a maintenance therapy with oral etoposide 25 mg daily. The toxicity appeared during the chemotherapy were assessed in all cases, but the blood concentration of the drug were measured in 5 cases on the first and the seventh day of treatment. While the peak plasma level (Cmax) was 0.92 +/- 0.43 microgram/ml on the first day and 1.02 +/- 0.30 micrograms/ml on the seventh day of chemotherapy, AUC was 12.3 +/- 5.41 micrograms.hr/ml and 11.9 +/- 4.52 micrograms.hr/ml on the first and the seventh day, respectively. Cumulative effect of the drug did not exist, since in any of these two measurements there was no significant statistical difference between values obtained on the first and on the seventh day. Regarding the toxicity of the drug, bone marrow suppression with abnormal reduction of peripheral white blood cells was observed. Though grade 2 adverse reaction was found in 6 cases, stopping drug administration for 2 weeks, enabled to re-administer the drug. Alopecia and liver or renal injury were not observed, and in spite of the presence of nausea and anorexia in one case, maintenance therapy could continue in all cases. Based on these results we concluded that etoposide can be safely administered as a maintenance therapy on out-patient basis.

Administration, Oral

Pulmonary infiltrates and skin pigmentation associated with sulfasalazine.

A patient with ulcerative colitis developed skin pigmentation and diffuse pulmonary shadowing without respiratory symptomatology, while taking sulfasalazine. The clinical picture and radiological abnormalities disappeared spontaneously on discontinuation of the drug. Histopathological studies from specimens taken by transbronchial biopsy showed bronchiolitis obliterans with fibrosing alveolitis. Sulfasalazine-induced lung disorder is an extremely rare entity which must be considered in all ulcerative colitis patients while on sulfasalazine therapy, despite the absence of pulmonary symptomatology.

Aged

[Obstructive pneumonitis in lung cancer patients--a retrospective study].

We evaluated the frequency and the backgrounds of lung cancer patients with obstructive pneumonitis. Among 84 cases of lung cancer, 35 presented with bronchial obstruction at bronchoscopy or on radiological studies. Of these 35 cases, 8 had infectious obstructive pneumonitis. This complication was observed more commonly in patients with squamous cell carcinoma. A comparative analysis of the immunological and nutritional states before the occurrence of bacterial complication was performed on patients with infectious obstructive pneumonitis and those with non-infectious obstructive pneumonitis. The serum concentration of total protein, albumin and total cholesterol was significantly lower in patients who subsequently developed bronchial obstruction and bacterial infection, compared to concentrations in patients with non-infectious obstructive pneumonitis. Similarly, there was significant decrease in the number of peripheral lymphocytes, and neutrophils as well as a significant reduction of the serum concentration of IgM in the group of patients with infectious complications. These results suggest that nutritional and immunological deficiencies, in association with local airway obstruction, may be determining factors in the occurrence of infectious obstructive pneumonitis in patients with lung cancer.

Aged

Serotypes of avian infectious bronchitis virus isolates from field cases in Japan.

Eight etiologic agents isolated from field cases in Japan were identified as isolates of infectious bronchitis virus by agar-gel diffusion, buoyant-density determination on sucrose-density centrifugation, and morphological study by electron microscope of the purified viruses. In studies of the antigenic relationships of the eight isolates and six known infectious bronchitis viruses, antigenic diversity of these viruses was recognized from the degrees of relatedness using a plaque reduction in the "constant-virus decreasing-serum" method.

Animals

Modification of three avian viruses passaged in Chinese hamster lung cells (Don) in pathogenicity to chicken embryo.

The Beaudette 42 strain of avian infectious bronchitis virus, Sato strain of Newcastle disease virus, and Uchida strain of avian reovirus were passaged in Chinese hamster lung cells (Don), and some properties were examined. The Don-passaged strains showed a difference in replication in Don and chicken embryo kidney cells in one-step growth curve examinations and a partial modification in pathogenicity to chicken embryos; nevertheless, neutralization tests revealed no serological alteration.

Animals