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Biomedical subjects

S Hoashi

Publications and source records attributed to S Hoashi.

13 recordsLinked to original sources

Phase I and pharmacokinetic study of carboplatin and paclitaxel with a biweekly schedule in patients with advanced non-small-cell lung cancer.

PURPOSE: A phase I study was conducted to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of carboplatin in combination with paclitaxel using a biweekly schedule in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: The pharmacokinetics of paclitaxel were determined preliminarily in some patients. The criteria for eligibility for study entry included histologically and/or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable disease. Paclitaxel was given in combination with a fixed dose of carboplatin at an area under the concentration-time curve (AUC) of 3 mg/ml x min, every 2 weeks. The starting dose of paclitaxel was 100 mg/m(2), and the dose was increased in increments of 20 mg/m(2). Three to six patients were allocated to each dose level. RESULTS: A total of 19 patients (11 male and 8 female) with a median age of 61 years (range 43-74 years) and a median ECOG performance status of 0 (range 0-1) were enrolled. The MTD of paclitaxel proved to be 160 mg/m(2), and the DLT was neutropenia, which improved well following treatment with G-CSF. Gastrointestinal toxicity was well tolerated. Of 17 patients who received four cycles or more, 7 (41%; 95% confidence interval 18.4-67.1%) responded to this combination therapy. The pharmacokinetics of paclitaxel did not differ from published data. CONCLUSIONS: The recommended dose for phase II study is paclitaxel 140 mg/m(2) with a carboplatin AUC of 3 mg/ml.min. This biweekly regimen is highly effective and acceptable, and the present data indicate that the regimen may be suitable for use on an outpatient basis.

Adult↗

[pncA gene mutations in clinical isolates of tubercle bacillus by polymerase chain reaction-direct sequencing method: in relationship to pyrazinamide resistance].

We screened clinical isolates of tubercle bacillus for mutations in the pncA gene, which encodes pyrazinamidase (PZase), by polymerase chain reaction (PCR)-direct sequencing method. Sixty-eight strains of tubercle bacillus were isolated from 32 patients with pulmonary tuberculosis. The patients were treated with antituberculous agents including pyrazinamide (PZA) for 2 months. Thirty-two of the 68 strains were isolated from sputum samples collected from the patients before treatment; 29 strains and 7 strains were collected after 1 month and 2 months of treatment, respectively. The pncA genes in these strains, were assessed for mutations by direct sequencing of PCR products using an automated sequencer. Similarly, we examined two clinical isolates (ka567 and minami22) of tubercle bacillus, determined to be deficient in PZase activity by the Wayne method. A PZA-sensitive strain (H37Rv, ATCC27294), and a PZA-resistant strain (H37Rv-PZA-R, ATCC35828) were used as negative and positive controls for mutations in the pncA gene, respectively. None of the 68 strains demonstrated any mutations in the pncA gene; however, the 2 PZase-deficient strains had missense mutations in the pncA gene resulting in an amino acid substitution from His82 to Arg in clone ka567, and from Ala171 to Val in clone minami22.

Adult↗

[Lung cancer with a sarcoid-like reaction in the primary tumor].

An 80-year-old woman was admitted to the hospital because of a nodular lesion in the right upper lobe of the lung. Transbronchial biopsy was performed and adenocarcinoma of the lung was confirmed by pathological examination. The tumor was resected by right upper lobectomy and was found to be a moderately differentiated tubular adenocarcinoma. Numerous non-caseating epithelioid cell granulomas were also found intermingled with the cancer cells. Metastasis was apparent in several regional lymph nodes but no granulomatous lesions were found in any lymph node, regardless of metastasis. These findings were compatible with a "sarcoid-like reaction" because there was no clinical evidence of generalized sarcoidosis or pulmonary mycobacterial infection. Although sarcoid-like reactions are occasionally associated with cancer, formation of an epithelioid cell granuloma inside the primary tumor is very rare. All the reported cases of a sarcoid-like reaction within the primary lung tumor so far were with adenocarcinoma. The sarcoid-like reaction may be a local immune response to the cancer cells.

Adenocarcinoma↗

[The influence of the alcohol and the low protein diet on rat pancreas].

We investigated the influence of alcohol and the low protein diet upon rat pancreas. Rats were separated in four groups, 1) Control diet group (Cont), 2) Alcohol diet group (Al), 3) Low protein diet group (Lp), 4) Low protein and alcohol diet group (Lp+Al). They were fed on isocaloric liquid diet compulsorily through the gastric tube. They were sacrificed 3, 6, 12 weeks after. By the light microscopic observation on the rat pancreas which were fed for 12 weeks, lipid droplets in the acinar cells were observed in all groups other than Cont. Apoptosis was founded in Lp and Lp+Al groups. Protein plugs were observed in all groups, and no relation was found between the plugs and the location of the injured acinar cells. By the electromicroscopic observation, in Lp+Al group, acinar cells were typically injured (ER dilation, atrophic nuclei, mitochondria degeneration, etc.) and mesenchymal cells appeared among acinar cells. These results suggest that alcohol causes pancreatic acinar cell injury directly, and relative low protein diet helps to turn it worse.

Animals↗

[Interleukin-6 and glucocorticosteroid responses to cardiopulmonary bypass].

The responses of interleukin-6 (IL-6), ACTH, cortisol, WBC, CRP to cardiopulmonary bypass (CPB) were studied in 5 patients who underwent elective CABG (N = 4) and AVR (N = 1). IL-6 started to increase from 3 h after the beginning of the operation at which aortic clamp was removed and reached a peak after 4 h at which CPB was withdrawn. ACTH also reached a peak after 4 h. The increase of cortisol started from 2 h when aorta was clamped, which was earlier than that of IL-6. IL-6 and ACTH fell sharply to pre-CPB levels before first postoperative day (1 POD) while cortisol remained high postoperatively. CRP level and WBC counts were maximum at 2 POD. The results suggest that the cortisol response to CPB is not only caused by IL-6, but also by other factors, such as IL-1 and TNF.

Adrenocorticotropic Hormone↗

Interstitial nephritis associated with glomerulonephritis in a patient with Hashimoto's disease and idiopathic portal hypertension.

A middle-aged women with hypothyroidism, idiopathic portal hypertension and nephrotic syndrome is presented. This unusual clinical appearance could not be explained as SLE by serological examinations. Pathohistological examinations showed "Banti's liver", Hashimoto's thyroiditis and diffuse proliferative glomerulonephritis with severe tubulo-interstitial nephritis. Immunohistochemical studies revealed IgA deposits in glomeruli. Electron microscopic study disclosed peculiar lucent areas of rarefaction with osmiophilic particles in tubular basement membranes. This tubulointerstitial nephritis was considered to be related to the immunological mechanism involving thyroid gland, liver and kidney disorders. This case thus had a clinically rare combination of these three.

Female↗

[Coagulation changes during liver resection].

Thrombin-antithrombin III complex (TAT) and plasminogen activator inhibitor (PAI) were measured during liver resection surgery in 8 patients. TAT and PAI activities of patients under liver resection were compared with those of 11 patients under resection of esophageal carcinoma. TAT activity increased during liver resection (P < 0.001) and reached 14 times (P < 0.001) of its control value in the recovery room. PAI activity was very stable during operation, but increased to twice (P < 0.01) of its control value in the recovery room. TAT activity of patients after liver surgery in the recovery room was (P < 0.05) more than twice of that of patients after esophageal surgery. We conclude that hypercoagulable state occurred during liver resection to a greater degree compared with that observed with esophageal surgery, and that its cause might be liver resection itself.

Antithrombin III↗

Changes in intramucosal pH and gut blood flow during whole body heating in a porcine model.

Heat stroke is a syndrome which reduces systemic vascular resistance and cardiac collapse. The gut plays an important role in shock. In hyperthermia, many of the same symptoms as heat stroke may be present, including inhibition of splanchnic vasoconstriction and endotoxemia. Furthermore, both conditions result in shock, in which the gut plays an important role. Detection of insufficient oxygenation of gut tissue, which sustains an earlier and more severe hypoxia, can warn of impending shock and can be performed by monitoring intramucosal pH (pHim). This index is very sensitive to tissue hypoxia and ischemia. In the present study both pHim, using tonometry, and gut blood flow during whole body heating (WBH) in pigs were measured. WBH was achieved by circulating warm water through a vinyl sheet covering the animal. Central venous pressure was maintained by fluid infusion. Body temperature was measured using a thermometer probe inserted into the right jugular vein. Mean arterial pressure, cardiac output and gut blood flow were also measured. pHim was evaluated using a tonometer placed into the midileum lumen. During WBH, cardiac index and mean arterial pressure increased, however systemic vascular resistance decreased. Gut blood flow was either maintained at the normal rate or increased. Intraarterial pH did not change significantly, however pHim significantly decreased from 7.30 at the beginning of WBH to approximately 7.05 after the body temperature reached 42.5 degrees C. These findings suggest that there was reduced oxygen delivery to the tips of the small intestinal villi during regional ischemia following WBH. In conclusion, insufficient tissue oxygen delivery as detected by a reduction in inramucosal pH is an important index in whole body heating.

Animals↗