Biomedical subjects

T Hirashima

Publications and source records attributed to T Hirashima.

At least 19 recordsLinked to original sources

PubMed2002

Substitution of Dmo1 with normal alleles results in decreased manifestation of diabetes in OLETF rats.

AIM: Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes in the Otsuka Long Evans Tokushima Fatty (OLETF) rat strain. To evaluate possible metabolic and pathological improvements generated by correction of the Dmo1 genetic pathway, we produced congenic lines, in which both OLETF Dmo1 alleles are replaced by the F344-derived genome. METHODS: Congenic animals were produced by introgressing F344-derived Dmo1 alleles into the OLETF rat. Congenic animals of the fourth generation (BC4) were intercrossed to obtain F1 animals (BC4:F1). Animals of the next generation, BC4:F2, were used for this study. We used 23 BC4:F2 males harbouring homozygous replacement of the OLETF Dmo1 region with the F344-derived genome. Seven animals with OLETF-derived Dmo1 alleles were used as controls. RESULTS: Dmo1-F344/F344 congenic rats showed significant decreases in body weight, abdominal fat weight, serum triacylglycerols, total cholesterol, food consumption and blood glucose after glucose loading (13%, 39%, 45%, 27%, 18% and 27% respectively; p < 0.05) compared with Dmo1-OLETF/OLETF animals. Furthermore, histopathological analysis of the kidney showed that mesangial sclerosis, hyalin deposits and deposition of PAS-positive substance were significantly lower in Dmo1-F344/F344 animals (p < 0.05). CONCLUSION: Improvements in metabolic parameters and histopathological scores show that correction of the Dmo1 genetic pathway in the diabetic and mildly obese OLETF rat strain produces wide-ranging therapeutic effects. Thus, this pathway might represent a new drug target also applicable to humans.

Animals↗

PubMed2001

Carboplatin calculated with Chatelut's formula plus etoposide for elderly patients with small-cell lung cancer.

OBJECTIVE: This dose escalation was conducted to evaluate the applicability of Chatelut's dosing, and to determine the efficacy and toxicity of carboplatin with etoposide in previously untreated elderly patients (>70 years) with small cell lung cancer. PATIENTS AND METHODS: Seventeen patients were treated with etoposide for 3 days and carboplatin calculated dose using Chatelut's formula on day 1 intravenously. The starting doses of etoposide on days 1 to 3, and carboplatin using the area under the concentration versus time curve (AUC) were 90 mg/m2 and 4 mg/ml x min, respectively. RESULTS: The median age was 77 years (range 71 to 87). Dose-limiting toxicity (DLT) was seen at level 4 (AUC 5 mg/ml x min of carboplatin and etoposide 100 mg/m2). Hematologic toxicity was the primary DLT. Grade 4 thrombocytopenia and Grade 4 leukopenia were observed at level 4. Non-hematologic toxicity was insignificant. The overall response rate was 94%. CONCLUSION: Etoposide at 100 mg/m2 and AUC of carboplatin of 4.5 mg/ml x min as calculated using Chatelut's formula every four weeks is the recommended dose for further phase II trials for elderly patients with small cell lung cancer.

Aged↗

PubMed2000

Decrease in triglyceride accumulation in tissues by restricted diet and improvement of diabetes in Otsuka Long-Evans Tokushima fatty rats, a non-insulin-dependent diabetes model.

With respect to the connection between triglyceride (TG) and non-insulin-dependent diabetes mellitus (NIDDM), previous reports have shown that TG accumulation in the liver and muscle is one of the causes of insulin resistance, and TG accumulation in pancreatic islets induces impairment of pancreatic beta-cell function. This experiment examined the relationship between an amelioration of hypertriglyceridemia (HTG), a decrease in TG accumulation in tissues, and an improvement of NIDDM by food restriction. In this experiment using Otsuka Long-Evans Tokushima fatty (OLETF) rats developing NIDDM and Long-Evans Tokushima Otsuka (LETO) rats as controls, sequential changes in body weight and TG content in tissue were measured and biochemical blood tests, an insulin euglycemic clamp test, and histopathologic examination of the pancreas and liver were performed. OLETF rats were allocated to a food-satiated group (satiated) or 30% food-restricted group (restricted). As a result, several findings were more evident in the restricted group than in the satiated group: (1) reductions in body weight and intraabdominal fat weight, decreases in plasma TG, insulin, and glucose levels, a decrease in the TG secretion rate, and an increase in plasma lipoprotein lipase (LPL) activity, (2) decreases in the TG content in the liver, pancreas, and muscle, (3) improvement of the glucose infusion rate (GIR), and (4) a marked reduction of TG accumulation in the liver and pancreatic islets on histopathologic examination. These results indicate that the improved HTG caused a reduction in TG accumulation in the liver and muscle, thereby improving insulin resistance. Moreover, the decrease in TG accumulation in pancreatic islets suggests an improvement of pancreatic beta-cell function.

Animals↗

PubMed2000

[Risk factors of anastomotic leak following operations for gastric cancer in the elderly].

The risk factors of anastomotic leak in the elderly following operations for gastric cancer were evaluated by multiple logistic model analysis. Data were taken from 705 operations over a 14-year period. The mean age of patients was 75.8 +/- 7.6 years. The significant risk factors for anastomotic leak were amounts of intra-operative bleeding and male gender. No other factors were significant, including age, preoperative associated diseases, preoperative nutritional states and postoperative complications, some of which were, however, significant factors by univariate analyses. We conclude that we should make every endeavor to lower the amount of intra-operative bleeding in order to prevent postoperative anastomotic leaks in the elderly, especially in male patients.

Adult↗

PubMed2000

[Analyses of factors preventing returning home in elderly patients on dialysis].

A significant number of elderly patients who begin dialysis are not able to return home even after attaining stable dialysis. The aim of the present study is to clarify the factors preventing returning home. Patients aged over 60 years who had newly started dialysis (103 cases) were studied. These were 58 men and 45 women. The age was 73 +/- 7 years (mean +/- standard deviation). In each patient, the cause of renal failure (non-diabetes/diabetes), nutritional state, complications, ambulation, cognitive function, urgency of the initiation into dialysis therapy, occurrence of access failure, presence or absence of the partner, presence or absence of members of the younger generation living in the same house, and the outcome (returning home or prolonged hospitalization) were surveyed. Of the 103 patients, 80 could return home, and 23 could not. First, we investigated the influence of the differences in each factor on the outcome. The subjects were divided into two groups by two categories in each factor. The numbers of patients who could not return home was calculated respectively. Comparisons were carried out by the chi 2 test. Statistically significant factors were ambulation (p < 0.0001), cognitive function (p < 0.0001), and cause of renal failure (p: 0.049). Multivariant logistic regression analysis was also performed using back-ground factors as explanatory variables and the outcome as a dependent variable. The factors presented by the nominal scale were converted to dummy variables. Statistically significant factors were ambulation (p < 0.0001), cognitive function (p: 0.001), and presence or absence of a partner (p: 0.012). Inability to walk, impaired cognitive function, and absence of a partner were the factors preventing returning home.

Aged↗

PubMed2000

[Analyses of factors prolonging the length of hospital stay in elderly patients beginning hemodialysis].

The aim of the present study is to clarify the factors causing prolongation of the length of hospital stay in elderly patients beginning hemodialysis. Patients aged over 60 years who had newly started hemodialysis (98 cases) were studied. These were 59 men and 39 women. The age was 73 +/- 7 years (mean +/- standard deviation). In each patient, the cause of renal failure (non-diabetes/diabetes), body mass index, comorbid conditions (cerebrovascular disease, ischemic heart disease, etc.), ambulation, cognitive function, urgency of the initiation of dialysis, occurrence of access failure, marital status, younger cohabitants, and the length of stay after initiation of dialysis were surveyed. The median and the mean of the length of stay were 37 and 49 days. Because of this disparity, a normal distribution of the length of stay could not be obtained. However, the distribution was transformed to close to normal by logarithmic conversion of the number of days. We used the log-converted value as the length of stay for statistical analyses. We investigated the influence of the differences of each factor on the length of stay. The subjects were divided into two groups for each factor. The mean and standard deviation of the length of stay was calculated respectively. Comparisons were carried out by unpaired t-test. Multiple regression analysis was also performed using background factors as explanatory variables, and the length of stay as a dependent variable. The factors presented by the nominal scale were converted to dummy variables. Eight variables in the unpaired t-test and seven variables in multiple regression analysis were statistically significant. All but one variable were common to both analyses. The gender was statistically significant only in the unpaired t-test. It could be explained by close correlation of gender with marital status. Access failure and urgent initiation of dialysis were dominant factors for the prolongation of the length of stay. Ischemic heart disease, diabetes, inability to walk, impaired cognitive function, and absence of a partner also prolonged the length of stay.

Aged↗

PubMed2000

Prognostic significance of hTERT expression in non-small cell lung cancer.

To investigate the prognostic role of hTERT expression in non-small cell lung cancer (NSCLC), we examined the expression of hTERT mRNA in tumor specimens from 68 patients with NSCLC using RT-PCR. The expression of hTERT was detected in 34 (50%) of 68 cancer tissues. There were no correlations between hTERT status and any common clinical features except age. Patients with hTERT expression had shorter survival than those without hTERT expression. Multivariate analysis showed that hTERT expression was an independent negative prognostic factor. These results suggest that expression of hTERT may be an independent prognostic factor for NSCLC patients.

Aged↗

PubMed1999

Examination of the pathogenesis of diabetic nephropathy in OLETF rats.

We conducted protein loading to examine the progression and pathogenesis of diabetic nephropathy. For this experiment, male OLETF, LETO, F344 and BN rats were used. This experiment was performed on rats between 5 and 30 weeks of age. Examination parameters included body weight, food intake, oral glucose tolerance test (OGTT), urinary protein level (UP), urinary albumin level (UA), glomerular filtration rate (GFR), kidney weights, light microscopy (LM) and electron microscopy (EM). In the protein-loaded OLETF group, the UP level was markedly increased 20 weeks or more after birth. In OLETF control group, GFR were higher than those in other strains. Glomerular hypertrophy and kidney weights were markedly increased in protein-loaded groups in OLETF rats. Thirty weeks after birth, EM showed that the number of polyethyleneimine (PEI) of the glomerular basement membrane (GBM) in protein-loaded OLETF group was significantly decreased compared to that in control group. These changes in OLETF rats were more marked in the protein-loaded group than those in the control group. LM showed that the number of exudative lesions with fibrin-cap in the protein-loaded OLETF group was significantly increased than those in control group. In OLETF rats, protein loading caused deterioration of nephropathy at 30 weeks of age. Therefore, it was demonstrated that not only blood sugar control but also protein intake factors play important roles in the deterioration of nephropathy in OLETF rats.

Albuminuria↗

PubMed1998

Phase II trial of carboplatin plus oral etoposide for elderly patients with small-cell lung cancer.

A phase II trial was conducted to evaluate the efficacy and toxicity of the Egorin's carboplatin dosing formula with 14-day oral etoposide in 38 elderly patients with small-cell lung cancer (SCLC). The overall response rate was 81%. Median survival times were 15.1 months for 16 limited-disease (LD) and 8.6 months for 22 extensive-disease (ED) patients. Myelosuppression was the principal side-effect. This regimen is an active regimen in the treatment of elderly SCLC patients.

Aged↗

PubMed1998

A disrupted cholecystokinin A receptor gene induces diabetes in obese rats synergistically with ODB1 gene.

Otsuka Long-Evans Tokushima fatty (OLETF) rats develop hyperglycemia, hyperinsulinemia, and mild obesity, which are characteristic of human non-insulin-dependent diabetes mellitus. We have shown that two recessive genes, ODB1 mapped on the X chromosome and ODB2 mapped on chromosome 14, are involved in the induction of the diabetes in OLETF rats. Recently we found that OLETF rats are the naturally occurring cholecystokinin type A receptor (CCKAR) gene knockout rats. In this study, we focused on the genotype of CCKAR gene and the ODB1 gene in regulation of glucose homeostasis in the F2 cross of the OLETF rats. Relatively high plasma glucose levels were observed in the F2 offspring with the homozygously disrupted CCKAR gene. A synergistic effect for increasing plasma glucose levels in F2 rats between disrupted CCKAR gene and the ODB1 gene was shown. The CCKAR gene was found to map very close to ODB2 by a linkage analysis using microsatellite markers. These results suggest that CCKAR gene maintains normoglycemia in rats.

Animals↗

PubMed1998

Combination of irinotecan and etoposide for treatment of refractory or relapsed small-cell lung cancer.

PURPOSE: To determine the response rate, survival, and toxicity of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, in refractory or relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Twenty-five patients with refractory or relapsed SCLC were entered onto the trial. All 25 patients had been pretreated with some form of cisplatin-based combination chemotherapy and had also received previous etoposide- or anthracyclinecontaining chemotherapy. The median time off chemotherapy was 6.7 months (range, 0.9 to 23.5). Patients were treated at 4-week intervals using CPT-11 (a starting dose of 70 mg/m2 intravenously on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3), with a subsequent dose based on toxicity. In addition, recombinant human granulocyte colony-stimulating factor (rhG-CSF; 2 microg/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration. RESULTS: All patients were assessable for toxicity and survival. Twenty-four patients were assessable for response. There were 14 partial responses (PRs) and three complete responses (CRs), for an overall response rate of 71% (95% confidence interval, 53% to 89%). The median response duration was 4.6 months. Median survival was 271 days. Major toxicities were myelosuppression (predominantly leukopenia) and diarrhea. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 56% and 20% of patients, respectively. Grade 3 to 4 diarrhea was observed in 4%. There was one treatment-related death due to severe myelosuppression. CONCLUSION: A combination of CPT-11 and etoposide with rhG-CSF support is an active therapy against refractory or relapsed SCLC and deserves to be studied more extensively in a phase III trial.

Adult↗

PubMed1998

[Two elderly patients with intestinal perforation caused by press-through package].

We report two cases of intestinal perforation caused by accidental swallowing of Press-Through Packages (PTP). The first case occurred in a 90-year-old woman with moderate dementia. She was admitted to our hospital because of abdominal pain and intestinal obstruction. She showed symptoms and sign of peritonitis and underwent abdominal surgery. The postoperative diagnosis was diffuse peritonitis due to a perforated rectal ulcer caused by the sharp corners of an accidentally swallowed PTP. The second case occurred in an 82-year-old woman with recurrent symptoms and signs of intestinal obstruction. She underwent abdominal surgery and the operation revealed an ileal perforation due to penetration by the sharp edge of a PTP. Both patients were discharged in good condition. PTPs are rapidly becoming popular as packaging for tablets and capsules. However, reports of accidental swallowing of PTPs have recently been increasing. In most cases, the PTPs were found in the esophagus and removed endoscopically. Progression of accidentally swallowed PTPs to the intestines is rare. However, when this occurs, the patient's condition becomes more serious. We propose that drugs should not be dispensed in PTPs but rather handed to the patients, especially to elderly patients, or when impossible, the corners of PTPs should be rounded.

Aged↗

PubMed1998

[Prognostic significance of alterations in telomeric repeat length in patients with pathological stage I-II non-small cell lung cancer].

UNLABELLED: The purpose of this study was to evaluate the correlation between alteration in telomere length and prognosis in patients with pathological stage I-II non-small cell lung cancer. We measured telomeric repeat length and telomerase activity by use of southern blot analysis of terminal restriction fragments and a non-radioactive ELISA-based assay, respectively. RESULTS: Alterations in TRF lengths were present in 17(29.8%) of 57 patients. Patients with altered TRF length had significantly shorter survival than did patients without (P = 0.0051). In multivariate analysis, only alteration in TRF length independently correlated with shortened survival (P = 0.0033).

Adult↗

PubMed1997

Transcutaneous needle biopsy of the lung.

PURPOSE: To evaluate the usefulness of transcutaneous needle biopsy (TCNB). MATERIAL AND METHODS: From May 1988 to December 1994, we performed TCNB under fluoroscopic control in 408 patients with mass lesions of the peripheral lung. The Surecut needle (1.5 mm) was selected mainly because of its ability to obtain specimens large enough for histological examination. Of the 408 patients, 286 had had previous bronchofiberscopic examinations but no definite diagnosis had been reached. RESULTS: A definite diagnosis was obtained by TCNB in 305 (74.7%) of 408 cases (251 malignant neoplasms, 54 benign lesions). In malignant neoplasms, the pathological diagnosis based on cytology and histology together was more reliable than that based on cytology alone. Although the complications of this procedure (such as pneumothorax) were within the range of acceptability, care should be taken to avoid air embolism and the seeding of cancer cells along the needle tract. CONCLUSION: TCNB with the Surecut needle is a useful procedure with relatively low risk.

Biopsy, Needle↗

PubMed1997

Impaired beta-cell function and deposition of fat droplets in the pancreas as a consequence of hypertriglyceridemia in OLETF rat, a model of spontaneous NIDDM.

Hypertriglyceridemia is known to be a feature of obesity-related NIDDM, but the patho-etiological significance of this association is obscure. The effects of triglycerides (TGs) on beta-cell function and morphological changes in pancreas were examined using in vivo and in vitro approaches in male OLETF rats at ages 6, 12, and 30 weeks, with their diabetes-resistant counterpart, LETO rats, as normal controls. The results showed that, in the fasting state, plasma TGs in OLETF rats were increased 2.5-fold at age 6 weeks, 3.3-fold at age 12 weeks, and 6.2-fold at age 30 weeks, compared with age-matched LETO rats. The TG content in islets from 12-week-old OLETF rats was significantly increased when compared with those from their age-matched counterparts, but this was not the case with the 6-week-old OLETF rats. Therefore, the islets from 6-week-old rats were cultured with either free fatty acids (FFAs; 1.0 mmol/l sodium oleate) or TG (5.0 mmol/l Intralipide) for 72 h. Several abnormalities in OLETF rats were evident, in contrast to the results from control LETO rats: 1) glucose-induced insulin secretion was more inhibited by either FFAs or TGs in the presence of 27.7 mmol/l glucose, a result associated, at least in part, with reduced glucokinase activity in the islets; 2) a marked elevation in TG content was found in the islets; and 3) the deposition of fat droplets in the enlarged islets, even in the beta-cells, was found by Oil Red O-insulin double staining at age 30 weeks. In conclusion, hypertriglyceridemia resulted in significant TG stores in the islets, which subsequently inhibited glucose-induced insulin secretion, at least in part, via reduced glucokinase activity in the islets. Fat droplets in islets, therefore, may play an important role in hastening the development of NIDDM in this rat model.

Animals↗

PubMed1997

[Parkinsonism and postoperative complications in the elderly].

The risk factors for postoperative morbidity and mortality in elderly patients with Parkinsonism after gastrointestinal surgery were evaluated by univariate and multivariate analyses in comparison to those of patients with cerebrovascular disease and to those of patients with no comorbid condition. Data were obtained on 36 patients with Parkinsonism (PK), 77 with cerebrovascular disease (CVD) and 120 with no comorbid condition (ND). All data were adjusted for age, sex and operative procedure. The postoperative morbidity rate was highest in the PK group (77.8%), followed by the CVD group (70.1%), and both differed significantly from the rate of the ND group (32.5%). Gastrointestinal and pulmonary complications and delirium were the major postoperative complications, and were significantly more common in the PK group than in the ND group. Patients in the PK group had the longest postoperative hospital stay, followed by those in the CVD and ND groups; the differences were significant between the PK and ND groups and between CVD and ND groups. The PK group had the highest operative and hospital mortality rates, and they differed significantly from the ND group. Hayashi's second method of quantification was used to assess the risk factors for postoperative death. The highest partial correlation coefficient was that found for postoperative pulmonary complication. We conclude that we should pay close attention to postoperative respiratory management, particularly in elderly patients with Parkinsonism, to prevent pulmonary complications and reduce postoperative mortality.

Aged↗

PubMed1997

[Home infusion therapy for cancer patients at a near-terminal stage--analysis of cases who died at home].

To improve the quality of life in cancer patients at a near-terminal stage, we assisted patients to stay home using a system for home infusion therapy (HIT) established at Osaka Prefectural Habikino Hospital in 1994. From April in 1995 to April in 1996, 25 patients were treated at home using the HIT system for longer than 7 days. Thirteen out of 25 patients still stayed at home even at a terminal stage and died in their residences. There was no difference either in the mean age or in the HIT duration between 13 patients who died at home and the remaining 12 patients who were readmitted to their hospitals before death. However, 47% of the patients who died at home had been told their diagnoses by doctors and realized their own prognoses, while only 17% of the patients who died in the hospital knew their diagnoses and prognoses. Seventy-seven percent of the patients who died at home were given home oxygen therapy (HOT), against 33% of the patients who died in the hospital. Furthermore, the patients who died at home were given more intensive care than the patients who died in the hospital, because the former had a larger family than the latter. In conclusion, HIT at a near-terminal stage and death at home may be more readily accepted by patients who know their diagnoses and prognoses and have a large family.

Adult↗

PubMed1997

p21 expression as a predictor for favorable prognosis in squamous cell carcinoma of the lung.

Although p21 WAF1/Cip1 expression has been detected immunohistochemically in non-small cell lung cancer (NSCLC), the associations between p21 expression and clinical characteristics are unknown. To determine the association between p21 expression and clinical features, p21 expression was immunohistochemically analyzed in paraffin-embedded tumor samples from 137 patients with curatively resected NSCLC. p21 expression, indicating normal p21 function, was detected in 48 (35.0%) of the 137 patients with curatively resected NSCLC and was detected more frequently in patients with stage I or II disease (40.2%) than in those with stage IIIA disease (22.5%; P = 0.0483). There was no difference in the positive rate between squamous cell carcinoma [SCC; 15 of 48 (31.3%)] and adenocarcinoma [30 of 77 (39.0%)]. For SCC, patients with tumors expressing p21 survived longer than did those with tumors negative for p21 expression; however, the corresponding survival time was not significant for adenocarcinoma. On the other hand, p53 expression, detected in 58 (42.3%) of these patients, did not act as any predictor for prognosis in either SCC or adenocarcinoma. Our findings suggest that the presence of p21 expression is associated with favorable prognosis in SCC and may be useful in obtaining candidates for adjuvant therapies from among patients with SCC.

Adenocarcinoma↗