Biomedical subjects
K Fukutake
Publications and source records attributed to K Fukutake.
[Thoracotomy as treatment for pneumothorax associated with pneumocystic carinii pneumonia in a patient with hemophilia A and the acquired immunodeficiency syndrome].
Pneumocystis carinii pneumonia is the most common respiratory infection in patients with the acquired immunodeficiency syndrome, and inhalation of pentamidine aerosol is currently used for secondary prophylaxis. A 16-year-old patient with hemophilia A and the acquired immunodeficiency syndrome had a spontaneous pneumothorax during inhalation of pentamidine aerosol for secondary prophylaxis of Pneumocystis carinii pneumonia. Tube thoracostomy and pleurodesis were done without success. Thoracotomy was done 27 days after admission. The patient tolerated the procedure well, and the postoperative course was uneventful. Grocott staining of tissue from the bronchopleural fistula revealed Pneumocystis carinii, which suggests that the pentamidine aerosol failed to control and active Pneumocystis infection in peripheral lung zones.
Substantial expression of glycoproteins IX and V on the platelet surface from a patient with Bernard-Soulier syndrome.
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[Phase III clinical trial of KRN8601 (rhG-CSF) for neutropenia in patients with human immunodeficiency virus infection].
The efficacy of KRN8601 for neutropenia associated with HIV infection was evaluated in 24 patients. KRN8601 was infused intravenously at a dosage of 200 micrograms/m2 for 14 consecutive days. Neutrophil counts recovered in 19 (90.5%) out of 21 evaluable patients by KRN8601 treatment. The concomitant myelosuppressive agents for the treatment of HIV infection and complications could be continued without dose reduction in 15 (88.2%) out of 17 patients. The clinical improvement was observed in 66.7% (12/18) of patients who were treated with anti-microbial agents for opportunistic infections which indicates that KRN8601 shows an additive effect on infections when it was given with anti-microbial agents. Adverse events and abnormal laboratory findings were observed in 3 and 7 patients, respectively, and they were reversible and tolerable. This study demonstrated that KRN8601 improved neutropenia with HIV infection, made possible to continue the full dose of myelosuppressive treatments and have additive effect on the treatment of secondary infections.
[Blood concentrations of thrombomodulin in patients with various diseases].
Concentrations of thrombomodulin in blood plasma were measured by a one-step sandwich enzyme immunoassay (EIA). The concentrations in normal healthy subjects were 9.9 +/- 2.9 ng/ml. The concentrations were found to be significantly higher in patients with SLE, RA and other collagen diseases in their active stages than at their non-active stages. The concentrations increased in patients with DIC, and significantly higher levels were observed when DIC was complicated by multiple organ failure. These findings indicate that plasma concentrations of thrombomodulin may be a useful parameter for vascular injuries caused by inflammatory processes or coagulation/fibrinolysis reactions.
[Fluctuations of tissue-type plasminogen activator.plasminogen activator inhibitor-1 complex in patients with DIC].
Plasma levels of tissue-type plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor-1 antigen (PAI-1:Ag), the active form of PAI-1 (active PAI) and t-PA.PAI-1 complex (PAI-C) were analyzed in 7 patients with disseminated intravascular coagulation (DIC) syndrome. The levels of t-PA:Ag and PAI-C decreased after amelioration of DIC in 6 patients whose underlying disease improved, but their PAI-1:Ag and active PAI showed various fluctuations. The levels of t-PA:Ag and PAI-C showed a good correlation of r = 0.885. The levels of t-PA:Ag or PAI-C showed an inversed correlation with platelet counts, and correlations with the levels of plasmin.alpha 2PI complex, D dimer and E fragments of FDP. It was considered that plasma levels of PAI-C reflected levels of t-PA released from the endothelial cells, which was related to acceleration of fibrinolysis in DIC patients with improved underlying disease. On the other hand, these levels remained high in a patient whose underlying disease did not improve after recovering from DIC. It was considered that the stimulation of endothelial cells by cancer cells continued to exert an effect.
Mechanism of the lipid-lowering effect of ethyl all-cis-5,8,11,14,17-icosapentaenoate.
The effect of highly purified ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) on cholesterol metabolism in rats was examined to clarify the mechanism of its hypolipidemic action. Pretreatment with EPA-E reduced the increase in plasma radioactivity after oral administration of [14C]cholesterol. The conversion of [14C]3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to [14C]mevalonic acid was significantly inhibited in liver microsomes obtained from rats treated with EPA-E. There was an increase in free cholesterol and a marked rise in the eicosapentaenoic acid (EPA) content of phospholipids in these microsomes. EPA-E restored the suppression of biliary secretion induced by feeding a casein-rich diet to bile duct-cannulated rats. Furthermore, when serum lipoprotein (d < 1.210) from rats given EPA-E was i.v. injected into normal rats, a more rapid elimination of cholesterol was observed as compared to that in rats injected with lipoprotein from EPA-E-untreated rats. This rapid clearance was found in the lipoprotein fractions of d < 1.006 and 1.006 < d < 1.063. These findings suggest that EPA-E has an inhibitory effect on intestinal cholesterol absorption and hepatic cholesterol biosynthesis, and an enhancing effect on hepatic biliary secretion. EPA-E would also seem to cause modification of serum lipoproteins, whereby their clearance from the serum is increased.
Phase I/II trial of didanosine (2',3'-dideoxyinosine) in hemophiliac patients with AIDS or AIDS-related complex.
Forty-three hemophiliacs with AIDS or ARC received a daily dose of 334 or 500 mg didanosine (2',3'-dideoxyinosine or ddI) orally in 2 divided doses in phase I/II, open-label clinical trial conducted in Japan. Twenty-eight patients completed 6 months of therapy. There was an increase in circulating CD4(+) cells in 19 valuable patients from 91 +/- 25 (mean +/- SE) at entry to 131 +/- 38 at 24 weeks of therapy P = 0.01; Wilcoxon signed rank). Fourteen of 37 patients met the criteria for CD4 rise >/= 50/mm3 rise or >/= 50% increase from entry values) for more than 4 consecutive weeks. Twenty patients were p24 positive at entry. Nine out of the 10 evaluable patients (90%) showed a decline in p24 antigen at weeks 20-24 (P = 0.02). Thirty-five patients had symptoms related to HIV-1 infection at entry. Twenty-seven patients reported improvements in constitutional symptoms during therapy. Nine patients presented with possible drug-related adverse effects, and didanosine was discontinued in 6 patients (one each with edema; abdominal pain with anorexia; hematuria with edema and rash; sense of abdominal distension with anorexia; diarrhea and abdominal pain; and irritability). One patient had a transient increase in serum amylase level to twice the upper limit of normal, but he continued to receive the drug. These data suggest that didanosine was generally well tolerated in hemophiliacs with AIDS or ARC, and its administration correlated with improvement in constitutional symptoms and laboratory findings. The adverse effects of didanosine seen in this population were moderate to mild, and no complications related to hemorrhagic diathesis were observed, although the relative risk of acute pancreatitis in this population (while not seen in the present study to date) requires more study.
Immunological abnormalities in HIV-free haemophiliacs.
Since some haemophiliacs manifest profound immunodeficiency with no evidence of human immunodeficiency virus type 1 (HIV) infection, we measured the circulating immune complex (CIC) level in sera obtained from haemophiliacs and addressed the question of whether viral infection is associated directly or indirectly with enhanced CIC production. While more than 90% of HIV-positive individuals had a high level of CIC, around 60% of seronegative ones also showed CIC levels comparable to those of seropositive patients. These sera activated fresh complement in vitro. The patients infected with either HIV or Hepatitis C virus (HCV) or both showed higher frequency and concentration of serum CIC than those free of either pathogens. It is worth noting, however, that 64% of patients with no evidence of infection with HIV or HCV produced significant amounts of CIC. Among the infectious viruses examined, parvovirus is considered as one of the pathogens associated with CIC synthesis, since all the haemophiliacs including the HIV-free patients who had been supplied with heated coagulation factors for several years from birth carried antibodies to parvovirus B19. Strikingly, 60% of the children in this category were positive for CIC, suggesting the possible contribution of parvovirus infection to CIC formation.
Establishment of HIV-1-producing cells from peripheral mononuclear cells cultured with normal human serum.
Normal human serum (NHS) contributed to the establishment of cells producing HIV-1 under the conditions of coculture of peripheral mononuclear cells (PMC) from HIV-1 seropositive patients and of PHA-prestimulated or -non-stimulated PMC from seronegative healthy donors. No addition of IL-2 and Polybrene was necessary. Since, in the case 90101, the mitochondrial displacement-loop DNA showed identical sequences in the established cells and the HIV-1 seropositive patient's cells, it can be asserted that the HIV-1-producing cells originated from the patient. These cells are still releasing HIV-1-virion more than one year after their establishment.
[Mycosis in AIDS].
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[Detection of HIV-1 proviral DNA in peripheral leukocytes by AMPLICOR HIV-1 test kit].
AMPLICOR HIV-1 test kits, which had been developed as an HIV-1 provirus detection test by PCR method, have been evaluated for its clinical diagnostic application. Sixty-six of HIV-1 antibody positive and 67 of HIV-1 antibody negative blood samples derived from hemophiliacs, who had received blood products, have been tested by AMPLICOR HIV-1. All of the results from AMPLICOR HIV-1 were consistent with those from antibody test and clinical aspects. Thirty-nine of HIV-1 antibody positive samples have been tested by AMPLICOR HIV-1 and virus isolation (culture method). Twelve of 39 (30.8%) were positive by virus isolation, and 39 of 39 (100%) were positive by AMPLICOR HIV-1. Two of new born infants from HIV-1 sero-positive mothers were tested by AMPLICOR HIV-1, and the result suggested that the kit would be useful for diagnosis of infants from sero-positive mothers. Based on these studies, AMPLICOR HIV-1 is considered as useful clinical diagnostic for HIV-1 proviral DNA detection.
[Fluctuation of plasma levels of fibrinogen degradation products, fibrin degradation products and total fibrin/fibrinogen degradation products in patients with DIC].
Ten patients with disseminated intravascular coagulation syndrome (DIC) were analyzed using three enzyme linked immunosorbent assays (ORGANON TEKNIKA, Belgium) for fibrin degradation products (FbDP), fibrinogen degradation products (FgDP) and total fibrin/fibrinogen degradation products (TDP). A significant elevation in each parameter and a significant depression of FgDP/FbDP (g/b) ratio were observed in the patients in early stage of DIC, comparing with normal individuals (p < 0.001 and p < 0.01). These results suggested that both fibrinolysis and fibrinogenolysis were marked accelerated, with a superiority in fibrinolysis in those patients. The levels of these parameters decreased and the g/b ratio increased with the passage of the clinical courses in five patients who were improved. Although in five deteriorated cases, the levels were kept high and their g/b ratio showed low continuously. These findings suggested that separated monitoring of fibrinolysis or fibrinogenolysis was useful to study patients with DIC and g/b ratio could be regarded as a helpful indication of therapeutic effects.
[Thrombocytopenia in HIV-1 seropositive hemophiliacs].
When platelet counts were compared in 1986 and 1992 in 117 anti-HIV antibody positive and negative hemophilia patients, a clear decrease was found in the positive group. In 1992 platelet counts < 150 x 10(9) were present in 23.5% of the positive group in contrast to 5.8% of the negative group. Comparing platelet counts with other clinical parameters, a positive correlation was found with cholinesterase and a negative correlation with IgG in both the positive and negative groups, while negative correlations with beta 2-microglobulin and platelet-associated IgG were found in only the positive group. These findings implicate the chronic liver dysfunction present in hemophilia patients, apart from HIV infection, in the decrease in platelet counts, with immunodeficiency playing an additional role in the positive group. In the treatment of a hemophilia B patient showing decreased platelet counts, these counts increased consistent with the administration of Acyclovir and Zidovudine. It was demonstrated that HSV-1 and HIV-1 antigen are present on the soluble platelets of this patient and are recognized by antibodies in the patient's serum.
[Evaluation of an enzyme-linked immunosorbent assay for the determination of prothrombin fragment F1.2 (Dade Prothrombin Fragment F1.2 ELISA: Baxter Diagnostics Inc., U.S.A.) using micro-titer plate].
Prothrombin fragment F1.2 (F1.2) is a new molecular marker indicating acceleration of blood coagulation. We evaluated a new assay of F1.2 measurement using a micro-titer plate (Dade Prothrombin Fragment F1.2 ELISA: Baxter Diagnostics Inc., U.S.A.). The assay obtained satisfactory results in intra-assay reproducibility test, inter-assay reproducibility test, dilution linearity test and in vitro recovery test. Normal values of plasma F1.2 were 0.16 +/- 0.09 nmol/l (mean +/- SD) in 108 healthy individuals. Differences in the levels between the sexes were not significant. In patients with DIC (n = 22), plasma F1.2 levels were significantly higher than in normal healthy individuals and were correlated with the levels of thrombin-antithrombin III complex. These findings suggest that this F1.2 assay using a micro-titer plate is clinically useful for the evaluation of the therapeutic effect and diagnosis of hypercoagulable states like DIC.
[Levels of serum lactate dehydrogenase and its isozymes with relation to clinical features of pneumocystis carinii pneumonia in acquired immunodeficiency syndrome patients].
The clinical courses of 9 patients with acquired immunodeficiency syndrome (AIDS) complicated by pneumocystis carinii pneumonia (PCP) were followed to investigate the clinical significance of the measurement of various parameters such as serum lactate dehydrogenase (LDH). The mean duration of symptoms before diagnosis was 20 days, and the median duration of therapy was 29.5 days. Serum LDH activity increased in 8 of 9 cases. The isozyme pattern in all cases was characterized by high LDH3 values from the early stage. However, inflammatory markers did not increase in most cases. There were good correlations between the levels of LDH, clinical course, and PaO2.