Effect of ozagrel, a selective thromboxane A2-synthetase inhibitor, on cerebral infarction in rats. Comparative study with norphenazone, a free-radical scavenger

The effects of ozagrel (CAS 82571-53-7), a thromboxane A2-synthetase inhibitor, and norphenazone (CAS 89-25-8), a free-radical scavenger, on cerebral infarction were assessed using the suture-induced middle cerebral artery occlusion (MCAO) model and a microthrombosis model. In the former model, the middle cerebral artery was occluded for 2 h, and the infarction area and volume were evaluated 24 h after the start of reperfusion. In the latter model, microthrombosis were induced by two injections of sodium laurate (interval, 2 days) into the internal carotid artery, and the neurologic deficits were evaluated on the day afer the 2nd injection. Ozagrel at 3 mg/kg decreased both the area and volume of the cortical infarction after ischemia-reperfusion of the middle cerebral artery. Ozagrel also had suppressive effects on the neurologic deficits in the microthrombosis model. Norphenazone at 1 and 3 mg/kg had no clear effects in either model. Since the suture-induced MCAO model and the microthrombosis model are models for occlusion-reperfusion of the major cerebral arteries and lacunar infarction, respectively, these results suggest a highly beneficial effect of ozagrel in the clinical therapy for stroke.     

Genomic analysis of a recently identified virus (SEN virus) and genotypes D and H by polymerase chain reaction

BACKGROUND/AIMS: SEN virus (SENV) was discovered in 1999 as a DNA virus with hepatotropic properties. Nine genotypes (A-I) have been identified with genotypes D and H being more prevalent in cases of chronic hepatitis. Attempts to determine whether SENV causes liver disease have been hampered by limited diagnostic testing. METHODS: In the present study, we developed two PCR based assays; a general SENV screening and genotype-specific assay. RESULTS: By screening PCR, the specificity for all SENV genotypes and SENV-related sequences was 20/20 (100%) with confirmation of the results being provided by genomic sequencing. With the genotype-specific PCR, specificities for SENV-D and SENV-H were 7/7 (100%) and 7/11 (64%), respectively. All screening PCR products were cloned and sequenced. The results of sequencing showed high genetic diversity in representative SENV genotypes. Five of twenty patients (25%) had mixed infections with several SENV genotypes. CONCLUSIONS: The screening PCR was useful for identifying cases of SENV infection. However, because of high genetic divergence and mixed co-infection, it was difficult to establish a specific method for genotype distinction. Hence, sequencing is still required for further investigations of SENV as a potential cause of liver disease.     

How can we improve the quality of health care in Japan? Learning from JCQHC hospital accreditation

The World Health Report 2000 placed Japan first for overall health system attainment: a surprising development considering that, aside from discussing excessive expenditure, health care professionals and the Health Ministry have paid little attention recently to the quality of health care. Japan's free access policy and the universal health care system have actually fostered a very relaxed attitude toward evaluation. Concerned about the possible risks to patient safety, physicians established a volunteer association to promote quality health care issues. Then in 1995, the Japan Council for Quality Health Care (JCQHC) was founded to implement the third party accreditation of hospitals. Concurrent with the formation of the JCQHC, the sharply rising costs of malpractice litigation motivated the authorities and medical facilities to work toward protecting patient safety at different levels. Despite the WHO's positive review, critics maintain that significant inequities still exist in Japanese health care. Examples include, financial inequities between private and public hospitals, and the number and quality of hospitals and physicians between rural and urban areas. To protect patient safety and improve the quality of care, every effort must be made to eliminate inequities in the health care system. JCQHC accreditation is an important tool for furthering these efforts.     

Smoking and colorectal cancer in a non-Western population: a prospective cohort study in Japan

BACKGROUND: The risk of colorectal cancer in relation to smoking habits has been examined mostly in Caucasians, and evidence for other ethnic groups is still scarce. METHODS: Our data came from the Japan Collaborative Cohort (JACC) Study. From 1988 through 1990, 25,260 men and 34,619 women aged 40-79 years completed a questionnaire on cigarette smoking and other lifestyle factors. Hazard ratios (HR) were estimated by fitting proportional hazards models. RESULTS: During the mean follow-up of 7.6 years through December 1997, we documented 408 incident colon cancers and 204 rectal cancers. We found a non-significant increase in colon cancer risk in male current smokers compared with never smokers. The multivariate-adjusted hazard ratios were 1.07 (95% confidence interval [CI]: 0.72-1.59) for ex-smokers and 1.23 (95% CI: 0.85-1.78) for current smokers. We however failed to observe a clear dose-response relationship between smoking intensity or duration and colon cancer risk. The adjusted hazard ratio was 1.07 (95% CI: 0.71-1.61) even for 40+ years of smoking. Almost no increase in colon cancer risk was detected for female smokers, and male smokers were not at an enhanced risk of rectal cancer. CONCLUSIONS: Cigarette smoking was not a strong risk factor for colorectal cancer even after a long-term exposure, although a weak association remains open to discussion.     

A silicone-based wire-reinforced tracheal tube with a hemispherical bevel reduces nasal morbidity for nasotracheal intubation

We tested the hypothesis that a silicone-based wire-reinforced tracheal tube with a hemispherical bevel is superior to a polyvinyl chloride (PVC)-based precurved tube with a conventional diagonal bevel for nasotracheal intubation. Eighty anesthetized paralyzed adults (ASA physical status I-II) requiring nasotracheal intubation for tonsillectomy were randomly allocated into two equal-sized groups for airway management with the silicone tracheal tube or PVC tracheal tube. Intubation was subdivided into three phases: 1). passage through the nose into the pharynx, 2). laryngoscope-guided passage into the glottic inlet, and 3). laryngoscope-guided passage into the trachea. A specific sequence of airway maneuvers was followed at each stage if it was unsuccessful. The number of attempts and intubation time were documented by an unblinded observer. The frequency of epistaxis and postoperative nasal complications was documented by blinded observers. There were no intubation failures. The number of attempts at pharyngeal (47 versus 56; P = 0.04) and tracheal (43 versus 55; P = 0.005) placement was smaller for the silicone tracheal tube, but the number of attempts at glottic placement was more (72 versus 49; P < 0.0001). Intubation time was similar. The frequency (32% versus 80%; P < 0.0001) and severity of epistaxis were less for the silicone tracheal tube. The total number of postoperative nasal symptoms was smaller for the silicone tracheal tube (10 versus 21; P < 0.05). We conclude that the pharyngeal and tracheal placement phases of nasotracheal intubation require fewer attempts with the silicone tracheal tube than the PVC tracheal tube but that the glottic placement phase requires more attempts. Nasal morbidity is less common with the silicone tracheal tube. IMPLICATIONS: The pharyngeal and tracheal placement phases of nasotracheal intubation require fewer attempts with a silicone-based wire-reinforced tracheal tube with a hemispherical bevel than with a polyvinyl chloride-based precurved tracheal tube with a conventional diagonal bevel, but the glottic placement phase requires more attempts. Nasal morbidity is less common with the silicone tracheal tube.     

The sympathomimetic actions of l-ephedrine and d-pseudoephedrine: direct receptor activation or norepinephrine release?

The basic mechanisms by which ephedrine is preferred over other vasopressors in obstetric anesthesia have not been clearly defined. We examined the sympathomimetic effects of l-ephedrine, currently used as a vasopressor, and d-pseudoephedrine, currently used as a decongestant. In anesthetized rats, l-ephedrine and d-pseudoephedrine caused dose-dependent increases in arterial blood pressure and heart rate, and these effects disappeared after destruction of the sympathetic nerve terminals with 6-hydroxydopamine (6-OHDA) pretreatment. The two ephedrine isomers produced concentration-dependent increases in tension of anococcygeal muscle and sinus rate of right atrium from rats. However, the anococcygeal and atrial responses to d-pseudoephedrine were abolished after 6-OHDA pretreatment, whereas approximately 50% of the responses to l-ephedrine were 6-OHDA-resistant. In human umbilical artery and vein, the two isomers failed to generate any contraction when given at the concentration that is capable of producing significant effects on anococcygeal and atrial tissues. Although direct adrenoceptor activation with l-ephedrine was detectable at tissue levels, the pressor response in vivo was entirely attributable to norepinephrine release from sympathetic nerves. This indirect mechanism could partly explain why l-ephedrine is better at increasing maternal arterial blood pressure while preserving the uteroplacental blood flow that is devoid of the involvement of the sympathetic innervation. IMPLICATIONS: The indirectly sympathomimetic property of l-ephedrine may be one of the mechanisms to explain why ephedrine is preferred over alpha-adrenergic agonists as a vasopressor for treatment of intraspinal anesthesia-induced hypotension in obstetrics.     

Impact of treatment extending to 60 Gy on the outcome of radiotherapy for nasopharyngeal carcinoma

PURPOSE: To clarify the impact of treatment duration on the outcome of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Forty-three patients with NPC were treated with definitive radiotherapy from January 1980 through May 1996. The male-to-female ratio was 32:11, and median age was 58 years (10-78 years). According to the fifth UICC classification, 4 patients were stage I, 12 were stage II, 6 were stage III, and 21 were stage IV. Twenty-nine patients received chemotherapy. Each patient was treated to various doses according to their disease extension. Thus, treatment duration was defined as the duration from the start of radiotherapy to the end of 60 Gy. The median follow-up period was 63 months (2-164 months). RESULTS: The 5-year overall and disease-free survival rates of all patients were 66% and 59%, respectively. The 5-year disease-free survival rates of the patients treated with the short treatment duration (< or = 8 weeks) and those treated with the long treatment duration (> 8 weeks) were 76% and 38%, respectively (p = 0.008). CONCLUSION: Long treatment duration may lead to poor treatment outcome in NPC.     

CT perfusion of the liver during selective hepatic arteriography: pure arterial blood perfusion of liver tumor and parenchyma

PURPOSE: To quantify pure arterial blood perfusion of liver tumor and parenchyma by using CT perfusion during selective hepatic arteriography. METHODS: A total of 44 patients underwent liver CT perfusion study by injection of contrast medium via the hepatic artery. CT-perfusion parameters including arterial blood flow, arterial blood volume, and arterial mean transit time in the liver parenchyma and liver tumor were calculated using the deconvolution method. The CT-perfusion parameters and vascularity of the tumor were compared. RESULTS: A complete analysis could be performed in 36 of the 44 patients. For liver tumor and liver parenchyma, respectively, arterial blood flow was 184.6 +/- 132.7 and 41.0 +/- 27.0 ml/min/ 100 g, arterial blood volume was 19.4 +/- 14.6 and 4.8 +/- 4.2 ml/100 g, and arterial mean transit time was 8.9 +/- 4.2 and 10.2 +/- 5.3 sec. Arterial blood flow and arterial blood volume correlated significantly with the vascularity of the tumor; however no correlation was detected between arterial mean transit time and the vascularity of the tumor. CONCLUSION: This technique could be used to quantify pure hepatic arterial blood perfusion.     

Leptin activation of corticosterone production in hepatocytes may contribute to the reversal of obesity and hyperglycemia in leptin-deficient ob/ob mice

Glucocorticoids have been implicated as pathophysiological mediators of obesity and insulin resistance and are regulated by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). This enzyme regenerates active corticosterone from inactive 11-keto forms. To assess the role of 11beta-HSD1-mediated synthesis of active corticosterone in leptin-related obesity and diabetes, we examined the peripheral effect of leptin on 11beta-HSD1 activity and gene expression in vivo and in vitro in hepatocytes from ob/ob mice and in liver of streptozotocin (STZ)-treated ob/ob mice. We observed an inverse relationship between hepatic 11beta-HSD1 expression and body weight in ob/ob mice and lean littermates. Leptin treatment of ob/ob mice markedly increased hepatic 11beta-HSD1 activity and mRNA expression. This induction of 11beta-HSD1 expression corresponded to reduced levels of circulating corticosterone and weight loss in ob/ob mice treated with leptin, indicating that impaired hepatic 11beta-HSD1 expression may contribute to the pathogenesis of obesity in ob/ob mice. In addition, leptin treatment of STZ-treated ob/ob mice caused marked increases in hepatic 11beta-HSD1 levels associated with decreased body weight and a significant reduction in hyperglycemia due to pancreatic beta-cell damage. Addition of leptin to ob/ob mouse primary hepatocytes led to a dose-dependent increase in 11beta-HSD1 mRNA expression. In contrast, leptin did not influence 11beta-HSD1 expression in primary hepatocytes from db/db mice, indicating that leptin regulation of 11beta-HSD1 expression is probably mediated by the functional leptin receptor. Thus, leptin appears to be an important metabolic signal that directly activates intrahepatic corticosterone production. These findings suggest that the liver-specific interaction of leptin with 11beta-HSD1 is involved in the development of obesity and insulin resistance in ob/ob mice.