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T Ura

Publications and source records attributed to T Ura.

17 recordsLinked to original sources

Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin.

NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit an efficient accumulation in solid tumours in mice. The purpose of this study was to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of NK911 and to evaluate its pharmacokinetic profile in man. NK911 was given intravenously to patients with solid tumours every 3 weeks using an infusion pump at a rate of 10 mg DXR equivalent min(-1). The starting dose was 6 mg DXR equivalent m(-2), and the dose was escalated according to the accelerated titration method. A total of 23 patients participated in this study. Neutropenia was the predominant haematological toxicity, and grade 3 or 4 neutropenia was observed at doses of 50 and 67 mg m(-2). Common nonhaematological toxicities were mild alopecia, stomatitis, and anorexia. In the dose identification part of the study, DLTs were observed at a dose of 67 mg m(-2) (grade 4 neutropenia lasting more than 5 days). Thus, this dosage level was determined to be the MTD. Infusion-related reactions were not observed in any cases. The C(5 min) and area under the concentration curve parameters of NK911 exhibited dose-dependent characteristics. Among the 23 patients, a partial response was obtained in one patient with metastatic pancreatic cancer. NK911 was well tolerated and produced only moderate nausea and vomiting at myelosuppressive dosages. The recommended phase II dose was determined to be 50 mg m(-2) every 3 weeks.

Aged↗

[Pacemaker infection caused by Staphylococcus schleiferi].

Pacemaker infection is one of the severe complication of pacemaker implantation. We report a case of pacemaker infection caused by Staphylococcus schleiferi which is a coagulase-negative staphylococcus, and its relation with human infection is not well characterized. In 1994, a 80-year-old male presented with a pacemaker pocket infection, cutaneous inflammation but no fever 2 months after insertion of a pacemaker. S. schleiferi was isolated from the pus. The patient was given cefazolin for 5 days. One month later he was readmitted because of cutaneous inflammation and the extruded generator was removed. S. schleiferi was isolated from the generator. After the patient was treated with cefazolin for 3 weeks, four consecutive wound cultures were all negative. A new generator was inserted on the same side. One month after re-insertion, the patient again presented a cutaneous inflammation, and S. schleiferi was isolated from the pus as well as the generator and the leads on their removal. Twenty-six days later, a new pacing system was inserted on the other side. There was no further recurrence of the infection. Removal of the entire pacing system was necessary to cure the infection. We expect further information of human infections caused by S. schleiferi.

Aged↗

Minimum alveolar concentration of sevoflurane that blocks the adrenergic response to surgical incision in women: MACBAR.

We have investigated the cardiovascular and plasma noradrenaline response to surgical incision under sevoflurane anaesthesia and determined the end-tidal concentration of sevoflurane that blocks the adrenergic response or responses to surgical incision (MACBAR) and changes in mean arterial pressure (MAP) in response to surgical incision (MACBCR) in 50% of women. We randomly assigned 64 female patients, aged 20-49 years, to eight groups according to end-tidal sevoflurane concentration: 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0% and 8.5%. All patients received only sevoflurane anaesthesia. An increase of 10% or more from prestress (incision) values of MAP or plasma noradrenaline concentration was considered a positive response. The probability of no response to stress was analysed using logistic regression to obtain the probability of no response vs. end-tidal sevoflurane concentration and the best-fit curve from the maximum likelihood estimators of the model parametes. MACBAR (mean +/- SE) was 8.0 +/- 0.2%, MACBCR was 7.9 +/- 0.2%. However, such high doses of sevoflurane cannot be used clinically because of their high toxicity. It may be preferable to combine sevoflurane with other anaesthetics to reduce haemodynamic responses to strong stimulation.

Adult↗

Effects of sevoflurane and isoflurane on renal function and on possible markers of nephrotoxicity.

BACKGROUND: Low-flow sevoflurane anesthesia is associated with increasing circuit concentrations of compound A, which is nephrotoxic in rats, but the effect of compound A and low-flow sevoflurane anesthesia on renal function in humans is unclear. The authors compared the effects of high- and low-flow sevoflurane and isoflurane anesthesia on renal function and on several possible markers of nephrotoxicity in humans. METHODS: Forty-two patients without preexisting renal disease underwent either low-flow isoflurane (1 l/min, n = 14), low-flow sevoflurane (1 l/min, n 14), or high-flow sevoflurane (6 l/min, n = 14) anesthesia for body-surface-area surgery scheduled to last at least 4 h. Twenty-four-hour urinary excretion of N-acetyl-beta-glucosaminidase (NAG), beta2-microglobulin, protein, glucose, blood urea nitrogen (BUN), and serum creatinine concentrations were measured before and after anesthesia. RESULTS: There were no differences in blood urea nitrogen, creatinine, and creatinine clearance among the three groups after anesthesia. Increased urinary N-acetyl-beta-glucosaminidase excretions were seen in the low-flow and high-flow sevoflurane groups, but not in the low-flow isoflurane group (P < 0.01). Ten patients in the low-flow sevoflurane group had 24-h urinary excretion of protein that exceeded the normal ranges after anesthesia, but only one patient in the isoflurane and none in the high-flow sevoflurane groups had this. CONCLUSIONS: Low-flow sevoflurane anesthesia was associated with mild and transient proteinuria. However, the observed proteinuria was not associated with any changes in blood urea nitrogen, creatinine, and creatinine clearance in these patients with no preexisting renal disease.

Acetylglucosaminidase↗

Minimum alveolar concentration of sevoflurane for tracheal extubation in children.

BACKGROUND: One advantage of tracheal extubation during deep anaesthesia is that respiratory complications are reduced. Sevoflurane is a suitable anaesthetic agent for children. This study was conducted to determine the minimum alveolar concentration of sevoflurane required to prevent cough or movement during and after tracheal extubation (MACextubation). METHODS: We studied 30 nonpremedicated children, aged 2-10 yr, undergoing plastic surgery. They were allocated randomly to five groups (end-tidal sevoflurane concentrations: 2.0, 2.5, 3.0, 3.5, 4.0%). After surgery, 60% nitrous oxide was discontinued and the target concentration of sevoflurane was maintained for at least 10 min in 100% oxygen, then the trachea was extubated to determine MACextubation. Logistic regression was used to estimate MACextubation of sevoflurane. RESULTS: MACextubation was 2.3 (0.2; standard error)% (95% confidence limits: 1.2% and 2.7%). CONCLUSIONS: Tracheal extubation in 50% of anaesthetized children age 2-10 yr may be accomplished without coughing or moving at 2.3% end-tidal concentration of sevoflurane.

Anesthetics, Inhalation↗

[In vitro antimycobacterial activities of pyrazinamide analogs: results of screening tests].

Attempting to find new drugs, which are more effective than pyrazinamide against Mycobacterium tuberculosis and also active against M. avium complex (MAC), we synthesized various pyrazinamide analogs and pyrazine derivatives and assayed their antimycobacterial activities in vitro against M. tuberculosis, M. avium and M. intracellulare. As is well known, pyrazinamide is more active in acidic medium than in neutral medium, but the growth of mycobacteria in acidic media is poor and inconsistent. Our preliminary experiments revealed that the relative antimycobacterial activities of test-drugs compared with pyrazinamide were essentially the same in pH5.5 medium as in pH6.0 medium. Therefore, Middlebrook 7H9 broth adjusted to pH6.0 was used throughout the present studies. Among 39 compounds synthesized, four drugs were insoluble in any of the solvent suitable for culture experiments and could not be tested, and remaining 35 compounds were screened. The growth of mycobacteria was followed by measuring the optical density at 530 nm (OD), and the OD of the culture in the presence of 200 micrograms/ml of the test-drug (OD-TD) was compared with that in the presence of pyrazinamide (OD-PZA). Each test-drug was ranked as A, B, C, D or E according to the ratio (OD-TD/OD-PZA) x 100%, if the ratio was equal to or less than 10%, 11-20%, 21-40%, 41-60% or 61-80%, respectively. Any drugs showing the ratio above 80% were excluded from further examinations. For M. tuberculosis, 11 drugs were ranked as A and 4 more as B. For M. avium, 2 drugs were ranked as A and 2 more as B. For M. intracellulare, 5 drugs were ranked as A and 2 more as B. Among highly ranked ones, 4 compounds, namely, pyrazinoic acid noctyl ester, pyrazinoic acid pivaloyloxymethyl ester, pyrazine thiocarboxamide and N-hydroxymethyl pyrazine thiocarboxamide were ranked as A against M. tuberculosis and M. intracellulare, and ranked as A, B or C against M. avium, and considered as hopeful candidates of new antimycobacterial drugs. Their bacteriostatic and bacteriocidal activities against M. tuberculosis as well as M. avium and M. intracellulare have been studied in details and reported in a separate paper. In vivo activities against murine experimental tuberculosis of these 4 drugs is now under investigation. Further, two drugs, N-hydroxy pyrazinamide and N-hydroxy pyrazinamide-4-oxide were ranked as A against M. tuberculosis and ranked A or B against M. intracellulare, and their more precise in vitro antimycobacterial activities are now under examination.

Antitubercular Agents↗

In vitro antimycobacterial activities of pyrazinamide analogs.

We synthesized various pyrazine derivatives and pyrazinamide analogs and assayed their antimycobacterial activities in vitro in order to find new drugs which are more active against Mycobacterium tuberculosis than pyrazinamide and also active against Mycobacterium avium and Mycobacterium intracellulare. Of the drugs synthesized, four drugs, namely, pyrazine thiocarboxamide, N-hydroxymethyl pyrazine thiocarboxamide, pyrazinoic acid n-octyl ester, and pyrazinoic acid pivaloyloxymethyl ester, were not only bacteriostatic but also bacteriocidal against these three species of mycobacteria in vitro under conditions in which pyrazinamide showed no or little activity. In conclusion, these four drugs are possible candidates for new antimycobacterial agents, and animal experiments are now under way.

Antitubercular Agents↗

Steroidal glycosides from Capsicum annuum.

Four new steroidal glycosides, named capsicosides A-D together with proto-degalactotigonin, were isolated from the roots and seeds of Capsicum annuum var. conoides and Capsicum annuum var. fasciculatum. On the basis of detailed chemical and spectroscopic evidence, the structures of capsicosides A-D were shown to be furostanol glycosides corresponding to gitogenin and tigogenin oligoglycosides. Capsicoside A was regarded as the same compound as the previously described capsicoside, whose structure now needs to be revised according to the data presented in this report.

Capsicum↗

Cyclic peptides, acyclic diterpene glycosides and other compounds from Lycium chinense Mill.

The chemical structures of four cyclic peptides, lyciumins A-D (1-4), three acyclic diterpene glycosides, lyciumosides I-III (5-7) and other three compounds, a tryptophan derivative glycoside (8), a monoterpene glycoside (9) and a steroidal glycoside (10) isolated from Lycium chinense, have been elucidated by a combination of chemical, 1H- and 13C-NMR, and mass spectrometric studies. Lyciumins are interesting because of their monocyclic octapeptides containing a novel C-N linkage between tryprophan N1 and glycine C alpha.

Amino Acid Sequence↗

[Experimental study of the viability of warm ischemic kidney. Relationship between ATP value in renal tissue by isotachophoresis and serum pyruvic acid to lactic acid ratio (P/L ratio)].

The viability of preserved kidney is considered to be evaluated by mitochondrial function. We used the three experimental conditions of WIT 60 minutes (group I), 90 minutes (group II), and 120 minutes (group III) using rabbit. We measured the ATP value of renal tissue as a direct method before ischemia (control), immediately before recirculation, and at one hour, two hours, one day, two days, four days and seven days after recirculation, using isotachophoresis (Tachophor LKB 2127), and as an indirect method, serum pyruvic acid, lactic acid and LDH values were measured simultaneously. The ATP value in groups I, II, and III before recirculation were 1/10 lower than controls. However, as WIT became longer, the recovery speed was diminished. The serum P/L ratio reflected the mitochondrial function in group III. (p less than 0.05) The measurement of ATP value by this method, although it is somewhat invasive, is a useful method with a simple technique and a short analysis time. The serum P/L ratio is considered not to reflect the mitochondrial function directly, but can be measured adequately in WIT 120 minutes.

Adenosine Triphosphate↗

A case of spontaneous rupture of ureter due to ureteral stone in G syndrome.

A case of spontaneous rupture of ureter with formation of urinoma due to ureteral stone, which was noticed in an infant with G syndrome, is described. Investigation revealed that the patient had bilateral vesicoureteric reflux. The urinary tract anomalies in G syndrome are discussed.

Abnormalities, Multiple↗

Acute hemorrhagic cystitis caused by adenovirus type 11 after renal transplantation.

A case of acute hemorrhagic cystitis caused by adenovirus type 11, which occurred in an allograft recipient 6 months after a living-related renal transplantation, is described. The patient lacked a neutralizing antibody to adenovirus type 11 before transplantation. Adenovirus type 11 was isolated from his urine and he developed a neutralizing and complement-fixing antibody to this virus. Although adenovirus type 11 isolates had been obtained from 2 of 18 renal allograft recipients, only 1 patient suffered acute hemorrhagic cystitis. Adenovirus type 11 may play a role in acute hemorrhagic cystitis in renal allograft recipients during immunosuppressive therapy.

Acute Disease↗

[Clinical experience with cefmenoxime (CMX) in complicated urinary tract infections].

Cefmenoxime (CMX) was intravenously administered to 106 patients with complicated urinary tract infection at a daily dose of 2-4 g for 5 days. An excellent response in overall clinical efficacy was seen in 15 cases (18.3%), a moderate response in 46 cases (56.1%) and poor response in 21 cases (25.6%). Pyuria was cleared in 20 cases (24.4%), decreased in 22 cases (26.8%) and unchanged in 40 cases (48.8%). Bacteriuria was eliminated in 41 cases (50.0%), decreased in 17 cases (20.7%), relapsed in 7 cases (8.5%) and unchanged in 17 cases (20.7%). Bacteriologically, 74 (76.8%) of the 95 strains isolated were eradicated by CMX, and 22 (23.2%) persisted. Side effects were observed in 3 (abdominal pain, diarrhea and elevation of trans amylase) of the 106 cases. Judging from the above results, CMX is considered to be a useful drug in the treatment of complicated urinary tract infections.

Adolescent↗

Captopril-associated granulocytopenia in hypertension after renal transplantation.

A living related kidney transplant recipient with normal renal functioning and hypertension secondary to renal artery stenosis was treated with captopril and developed reversible granulocytopenia. Complications caused by captopril, an angiotensin converting enzyme inhibitor, have been reported previously in hypertensive patients with systemic lupus erythematosus or with renal artery stenosis after renal transplantation. It is recommended that this drug be used with caution in this setting.

Adult↗