PubMed Health⌕ Search

Biomedical subjects

R Hasegawa

Publications and source records attributed to R Hasegawa.

At least 19 recordsLinked to original sources
PubMed2006

Pediatric susceptibility to 18 industrial chemicals: a comparative analysis of newborn with young animals.

We comprehensively re-analyzed the toxicity data for 18 industrial chemicals from repeated oral exposures in newborn and young rats, which were previously published. Two new toxicity endpoints specific to this comparative analysis were identified, the first, the presumed no observed adverse effect level (pNOAEL) was estimated based on results of both main and dose-finding studies, and the second, the presumed unequivocally toxic level (pUETL) was defined as a clear toxic dose giving similar severity in both newborn and young rats. Based on the analyses of both pNOAEL and pUETL ratios between the different ages, newborn rats demonstrated greater susceptibility (at most 8-fold) to nearly two thirds of these 18 chemicals (mostly phenolic substances), and less or nearly equal sensitivity to the other chemicals. Exceptionally one chemical only showed toxicity in newborn rats. In addition, Benchmark Dose Lower Bound (BMDL) estimates were calculated as an alternative endpoint. Most BMDLs were comparable to their corresponding pNOAELs and the overall correlation coefficient was 0.904. We discussed how our results can be incorporated into chemical risk assessment approaches to protect pediatric health from direct oral exposure to chemicals.

Age Factors↗
PubMed2005

A literature search on pharmacokinetic drug interactions of statins and analysis of how such interactions are reflected in package inserts in Japan.

BACKGROUND AND OBJECTIVES: Statins (HMG-CoA reductase inhibitors) are one of the most widely prescribed classes of drugs throughout the world, because of their excellent cholesterol-lowering effect and overall safety profile except for rare but fatal rhabdomyolysis arising either directly or indirectly by pharmacokinetic interactions with certain other drugs. As package inserts in pharmaceuticals are the primary source of information for health care providers, we carried out a literature search to examine how crucial information was provided in package inserts of five statins approved in Japan (simvastatin, atorvastatin, fluvastatin, pravastatin and pitavastatin). METHODS: A MEDLINE search from 1996 to June 2004 was carried out to identify studies on clinical pharmacokinetic drug interactions for the five statins. We mainly collected information on area under plasma concentration (AUC) following co-administration of statins with other drugs. The current package inserts used in Japan were obtained from the website of the Pharmaceutical and Medical Device Agency whereas USA package inserts were obtained from the Food and Drug Administration website. RESULTS: The majority of package inserts listed the drugs that interacted with statins with most describing the risk of rhabdomyolysis because of the possibility of increases in blood concentration. However, quantitative information such as change in AUC was provided in only a few cases. Instructions for dosage adjustment are seldom provided in the Japanese package inserts. USA package inserts list almost identical drug interactions as the Japanese package inserts, although they contain more quantitative data, especially for typical cytochrome P450 (CYP) inhibitors. CONCLUSION: All pharmacokinetic drug interactions including relevant quantitative data for potential effectors and details on mechanisms of interaction need to be given in package inserts as soon as the information becomes available, to ensure safe and proper use of the drugs concerned. Including such information in the package insert will be an extremely valuable aid for health care providers.

Area Under Curve↗
PubMed2003

Comparison between tube compensation and pressure support ventilation techniques on respiratory mechanics.

In the intubated patient, the presence of an endotracheal tube increases the work of breathing during spontaneous breathing. The tube compensation technique was developed as a new ventilator mode that can compensate for that additional the work of breathing. We investigated the respiratory parameters during the pressure support ventilation 0, 5, 10 cmH2O and tube compensation 100% modes of the Puritan Bennett 840 ventilator in ten postoperative patients who had undergone radical surgery for oesophageal cancer. Measurements were performed just before extubation. The tidal volume, respiratory rate and other respiratory parameters were measured with a Ventrak respiratory monitor, and the duty ratio, mean inspiratory flow, and rapid shallow breathing index were calculated. In particular, we performed a comparison between pressure support ventilation 5 cmH2O and tube compensation 100%, because pressure support ventilation 5 cmH2O is the usual ventilating mode before the extubation in our intensive care unit. The tidal volume of pressure support ventilation 10 cmH2O was significantly larger and the respiratory rate was significantly lower than the other three modes. There was no significant difference in the minute volume, tidal volume, and respiratory rate between pressure support ventilation 5 cmH2O and tube compensation 100%. The duty ratio of pressure support ventilation 10 cmH2O was significantly smaller than the other three modes. There was no significant difference in the duty ratio and rapid shallow breathing index between pressure support ventilation 5 cmH2O and tube compensation 100%. It was concluded that the assist levels of pressure support ventilation 5 cmH2O and tube compensation 100% were almost equal for clinical purposes.

Aged↗
PubMed2001

Inhibition of apoptosis by pentachlorophenol in v-myc-transfected rat liver epithelial cells: relation to down-regulation of gap junctional intercellular communication.

Pentachlorophenol (PCP), a promoter of murine hepatocarcinogenesis, inhibits gap junctional intercellular communication (GJIC) in rat liver epithelial cells in vitro. To test the hypothesis that both inhibition of GJIC and apoptosis contribute to tumor promotion, we investigated the effect of PCP on both GJIC and serum deprivation-induced apoptosis in v-myc-transfected rat liver epithelial cells. The results showed that PCP inhibited apoptosis, as measured by the TUNEL assay and DNA ladder formation. Inhibition of apoptosis was associated with a decrease in GJIC. The study demonstrated that PCP has a potential for inhibiting apoptosis and GJIC, supporting the hypothesis.

Animals↗
PubMed2001

Mitral stenosis and regurgitation with systemic lupus erythematosus and antiphospholipid antibody syndrome.

Cases of valvular disease accompanied by systemic lupus erythematosus and antiphospholipid antibody syndrome are uncommon. Here, we present a surgical case of mitral stenosis and regurgitation with systemic lupus erythematosus and antiphospholipid antibody syndrome. Mitral valve replacement was performed, and the postoperative course was uneventful. Pathohistological findings of the mitral valve showed degenerative change due to chronic inflammation, proliferative fibrous change and calcification without thrombus formation.

Antiphospholipid Syndrome↗
PubMed2001

Narcolepsy and other non-SAS hypersomnia in sleep breathing disorders clinic.

Four of the 708 snorers (0.56%), referred to our sleep breathing disorders clinic for the past 2 years were diagnosed as having narcolepsy-cataplexy. Detecting HLA DRB1*1501/DQB1*0602 positive was informative for differentiating genuine narcolepsy from non-sleep apnea syndrome (non-SAS) hypersomnia in our clinic. A non-SAS obese boy, diagnosed as having essential hypersomnia syndrome, was found to be HLA DRB1*1502/DQB1*0601 positive. His hypocretin concentration was 206 pg/mL in the cerebrospinal fluid.

Adolescent↗
PubMed2001

Effects of physiological cardiac pacing on sleep-disordered breathing in patients with chronic bradydysrhythmias.

In six patients with chronic bradydysrhythmias, polysomnographies were performed before cardiac pacemaker implantation and over the week following implantation. A patient with third-degree atrioventricular block (AVB) and two patients with sinus node dysfunction (SND) were associated with sleep-disordered breathing (SDB). Their cardiac pacemaker therapies, with the increase in the average heart rate, led to a reduction of apnea-hypopnea index and/or an improvement of Cheyne-Stokes breathing. It seems that chronic bradydysrhythmia is one of the causative factors leading to SDB.

Aged↗
PubMed2001

The successful management of thoracoscopic thoracic duct ligation in a compromised infant with targeted lobar deflation.

IMPLICATIONS: We describe the successful management of thoracoscopic thoracic duct ligation in a 2.5-kg compromised infant by using selective lobar-bronchial blockade. The technique reduces the risk of intraprocedural physiologic impairment, allowing the benefits of otherwise minimally invasive thoracoscopic procedures, even when the conditions of children are severely compromised.

Chylothorax↗
PubMed2001

Differences in respiratory parameters during continuous positive airway pressure and pressure support ventilation in infants and children.

The extubation criteria of pressure support ventilation (PSV) in infants and children were not yet established. We studied the differences in respiratory parameters during continuous positive airway pressure (CPAP) using a constant flow type ventilator and PSV using a demand valve type ventilator. Nineteen children (1.9+/-2.9 years old) who were ready to extubate were studied. All patients had recovered from their respiratory failure and had finished the weaning process of the ventilatory support. They were scheduled for extubation on the next day when their ventilatory mode had attained to a PSV of 3 cmH2O with a positive end-expiratory pressure (PEEP) of 3 cmH2O. On the extubation day, tidal volume (TV) and respiratory frequency (RR) were measured with a respiratory monitor at two modes (CPAP of 3 cmH2O and PSV), and the duty ratio (DR) and mean inspiratory flow (MF) were calculated. The sequence of the ventilatory mode was random. No case required reintubation. TV was 61.6+/-54.9 during CPAP and 67.7+/-61.4 ml during PSV, and RR was 38.5+/-10.6 and 37.1+/-8.8 beats/min., respectively. DR was 0.382+/-0.067 and 0.359+/-0.085, and MF was 96.6+/-78.3 and 101.0+/-69.0 ml/sec., respectively. The measured parameters and calculated values showed no significant difference between CPAP and PSV. It was found that the respiratory parameters were almost the same with CPAP and PSV immediately before the extubation, and the previous extubation criteria of CPAP can be used.

Blood Gas Analysis↗
PubMed2001

Evaluation of tube compensation in the Bennett 840 ventilator--a new ventilatory mode to support spontaneous breathing.

Respiratory care patients frequently require intubation with an endotracheal tube (ETT). Unfortunately, the ETT introduces a pressure drop (deltaPETT) that depends on the respiratory flow rate, thus increasing the work of breathing (WOB). Pressure support ventilation (PSV) cannot adequately compensate for this added WOB, because the degree of inspiratory assistance by PSV is fixed. Therefore, a technique called tube compensation (TC) has been developed to address deltaPETT. We examined the performance of TC and compared it with PSV of 5 cm H2O. The experimental system was constructed from a simulator, a test-lung, flow sensors, and a Bennett 840, and the respiratory parameters were studied. ETTs with IDs 6.5 and 8.0 mm were used. The quadratic approximation obtained for deltaPETT in the 6.5-mm ETT was 2.316 x flow + 7.910 x flow2, while that for the 8.0-mm ETT was 1.881 x flow + 3.353 x flow2. The maximum inspiratory flow (MIF) increased significantly with increasing TC, but tidal volume and inspiratory time did not show marked changes. The MIF for TC of 100% was larger than that for PSV of 5 cm H2O, when the 6.5-mm ID was used, but there was no significant difference between these modes when an ID of 8.0 mm was used. For both the 6.5 and 8.0-mm IDs, the PV loop corresponding to 100% TC was larger than that for PSV of 5 cm H2O. TC only compensated for the WOB caused by the ETT, whereas PSV compensated for the WOB caused by the ETT and the demand valve system. In clinical use, the differences between TC and PSV will demand attention.

Humans↗
PubMed2001

Comparative study of toxicity of 4-nitrophenol and 2,4-dinitrophenol in newborn and young rats.

The toxicities of 4-nitrophenol and 2,4-dinitrophenol in newborn and young rats was examined and the susceptibility of newborn rats was analyzed in terms of presumed unequivocally toxic and no observed adverse effect levels (NOAELs). In the 18-day repeated dose newborn rat study, 4-nitrophenol was orally given from Day 4 to Day 21 after birth but did not induce any toxicity up to 160 mg/kg in the main study, although it induced death in one of six males at 160 mg/kg, and three of six males and one of six females at 230 mg/kg in a prior dose-finding study. In the 28-day repeated dose oral toxicity study starting at 6 weeks of age, 4-nitrophenol caused the death of most males and females at 1,000 mg/kg but was not toxic at 400 mg/kg except for male rat-specific renal toxicity. As unequivocally toxic levels were considered to be 230 mg/kg/day in newborn rats and 600 to 800 mg/kg/day in young rats, and NOAELs were 110 mg/kg/day in newborn rats and 400 mg/kg/day in young rats, the susceptibility of the newborn to 4-nitrophenol appears to be 2.5 to 4 times higher than that of young animals. In the newborn rat study of 2,4-dinitrophenol, animals died at 30 mg/kg in the dose-finding study and significant lowering of body and organ weights was observed at 20 mg/kg in the main study. In the 28-day young rat study, clear toxic signs followed by death occurred at 80 mg/kg but there was no definitive toxicity at 20 mg/kg. As unequivocally toxic levels and NOAELs were considered to be 30 and 10 mg/kg/day in newborn rats and 80 and 20 mg/kg/day in young rats, respectively, the toxicity of 2,4-dinitrophenol in newborns again seems to be 2 to 3 times stronger than in young rats. Abnormalities of external development and reflex ontogeny in the newborn were not observed with either chemical. Based on these results, it can be concluded that the toxic response in newborn rats is at most 4 times higher than that in young rats, at least in the cases of 4-nitrophenol and 2,4-dinitrophenol.

2,4-Dinitrophenol↗
PubMed2001

[Perioperative management of the patient with von Willebrand's disease].

A 67-year-old man with von Willebrand's disease, was referred to our hospital for operation of the lung cancer. He underwent right upper lobectomy of the lung and mediastinal lymph node dissection under general anesthesia. Three days before surgery, 1-desamino-8-D-arginine-vasopressin (DDAVP) was infused with good response of bleeding time shortening from 6 minutes to 3 minutes. Therefore, immediately before operation, DDAVP was infused. During the operation bleeding tendency was observed. Heat-treated factor VIII concentration and fresh frozen plasma were administered. Bleeding tendency was controlled. Total blood loss was 613 ml. During intraoperative and postoperative period, factor VIII activity and von Willebrand factor (vWF) activity were kept at adequate levels (factor VIII: 105-150%; vWF: 65-225%). The postoperative course was uneventful and he was discharged 18 days after the operation.

Aged↗
PubMed2000

Prevention of v-Ha-Ras-dependent apoptosis by PDGF coordinates in phosphorylation of ERK and Akt.

In some v-Ha-ras-transfected cell lines, serum deprivation results in apoptosis. Clarification of the molecular mechanisms by which oncogenic Ras controls susceptibility to apoptosis may assist in the development of effective therapies against human cancer with oncogenic ras gene. In this report, we established a v-Ha-ras-transfected human fibroblast clone, R1. In R1 cells, induction of v-Ha-Ras enhanced susceptibility to cell death under serum-deprived conditions. Ladders of cellular DNA were identified only when oncogenic ras was induced under serum-deprived conditions. Platelet-derived growth factor (PDGF) precluded DNA fragmentation of serum-deprived v-Ha-ras-transformed cells. Under serum-depleted conditions, the amounts of activated ERK and Akt decreased as compared with those under serum-containing conditions. The decreased levels of activated ERK and Akt were restored by the addition of PDGF. Inhibition of phosphorylated-ERK and Akt resulted in renewed susceptibility to cell death. These results indicate that failure of signal transduction of oncogenic Ras by the deficiency of growth factors such as PDGF causes v-Ha-Ras-dependent apoptosis.

Androstadienes↗
PubMed2000

Effect of mental stress on left ventricular ejection fraction and its relationship to the severity of coronary artery disease.

To evaluate the relationship between the mental stress-induced decrease in left ventricular ejection fraction (LVEF) and the severity of exercise-induced ischaemia, 20 patients with stable coronary artery disease (CAD) underwent radionuclide ventriculography during mental stress testing and stress myocardial perfusion single-photon emission tomography (SPET). We also examined whether changes in haemodynamic and neurohormonal parameters are related to changes in LVEF during mental stress. The LVEF decreased from 54.8% +/- 17.7% to 49.8% +/- 16.2% with mental stress (P < 0.0005). Ten of the 20 patients (50.0%) had a > or = 5% decrease in LVEF The remaining ten patients had no or a <5% decrease in LVEF There was a significant correlation between the change in LVEF during mental stress and the size of the reversible defect on stress myocardial perfusion SPET (r = -0.80, P < 0.0005), with close regional correspondence (75% identical). This correlation was less strong in the 12 patients with a total defect score at rest of <10 (r = -0.69, P = 0.014) than in the eight patients with a total defect score at rest of > or = 10 (r = -0.94, P = 0.001). The changes in blood pressure and heart rate were not significantly correlated with the change in LVEF, but the percent change in adrenaline concentration correlated with the change in LVEE It is suggested that mental stress impairs systolic function by inducing transient myocardial ischaemia. The effect of neurohormonal responses during mental stress on LV systolic function may also be important in patients with CAD.

Aged↗
PubMed2000

Combined therapy with hypothermia and anticytokine agents in influenza A encephalopathy.

Two children with influenza A-related encephalopathy were treated with a combination of mild hypothermia (deep body temperature of the forehead: 35 degrees C) and anticytokine agents (high-dose methylprednisolone and ulinastatin), while receiving amantadine. One of the cases exhibited acute necrotizing encephalopathy on computed tomography (CT). Although no severe complications occurred, correctable hypokalemia and hyperglycemia occurred in both cases. Both patients recovered without any neurological sequelae. Our therapeutic protocol appears to be effective for managing influenza A-related encephalopathy.

Amantadine↗
PubMed2000

Increase in ultraviolet sensitivity by overexpression of calpastatin in ultraviolet-resistant UVr-1 cells derived from ultraviolet-sensitive human RSa cells.

Human RSa cells are highly sensitive to apoptotic-like cell death by ultraviolet irradiation (UV) while UVr-1 cells are their variant with an increased resistance to UV. Three days after UV at 10 J/m2, the viability of RSa cells was approximately 17% while that of UVr-1 cells was 65%. This different survival might reflect apoptotic cell death since apoptosis-specific DNA ladder was more clearly observed in RSa cells than in UVr-1 cells after UV. Addition of ALLN/calpain inhibitor I to the culture medium after UV resulted in similar survival (14 - 18%) between RSa and UVr-1 cells. Immunoblot analysis showed down-regulation of protein kinase CTheta, Src, Bax and mu-calpain after UV was more prominent in UVr-1 than in RSa cells. Activated mu-calpain appeared within 1 h post-UV only in UVr-1 cells. The expression of calpastatin, a specific endogenous inhibitor of calpain, was higher in RSa than in UVr-1 cells. To further examine the role of calpain in UV-induced cell death, cDNA of human calpastatin was transfected into UVr-1 cells. The results showed that overexpression of calpastatin suppressed down-regulation of Src, mu-calpain and Bax. Concomitantly, colony survival after UV was reduced in calpastatin-transfected cells as compared to vector control cells. Our results suggest that activation of calpain might account for, at least in part, the lower susceptibility to UV-induced cell death in UVr-1 cells.

Apoptosis↗
PubMed2000

Sleep apnea syndrome in patients with pulmonary thromboembolism.

Seven patients (one man and six women) with a diagnosis of pulmonary thromboembolism (PTE) were examined by polysomnography in order to clarify the relationship between sleep-related breathing disorders and PTE. In the chronic stage of PTE, sleep apnea syndrome (SAS) was recognized in two patients (a man and a woman) among the subjects. Four of the five patients without SAS showed nocturnal hypoxemia. The female predominance was different from ordinary SAS without the disease background of PTE even though PTE is accompanied by hypoxemia and pulmonary hypertension like SAS. A pathophysiological relationship between PTE and SAS was not found in this study.

Aged↗