Effects of tizanidine for refractory sleep disturbance in disabled children with spastic quadriplegia

Tizanidine is a centrally acting alpha-2 adrenoreceptor agonist widely used in the treatment of spasticity in patients with cerebral or spinal injury, and it is causing drawsiness in some of them. Based on these drug actions, we administered tizanidine to 21 spastic quadriplegic children with severe sleep disturbance not improved by conventional therapies. All these patients were showing abnormalities of both the induction and maintenance of sleep. The dosage of tizanidine was 0.1 to 0.2 mg/kg/day, divided into two or three doses. If daytime drowsiness was severe, tizanidine admistration was restricted to just prior to bedtime. In 13 patients (61.9%), we found improvement in sleep induction and/or maintenance. Moreover, patients' families were satisfied with the treatment. There were no detectable side effects except facial pallor in two patients (9.5%) whose treatment was discontinued. Severe muscle hypertonia causes severe pain, which generates strong sympathetic nerve activity and subsequent sleep disturbance. We consider that tizanidine has direct effects on the induction of sleep, and promotes muscular relaxation bringing about good sleep. We conclude that tizanidine is useful for the treatment of refractory sleep disturbance in spastic quadriplegic patients.     

Indomethacin, but not Helicobacter pylori, inhibits adaptive relaxation in isolated guinea-pig stomach

Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) are major factors in gastritis and peptic ulcer However, the role of NSAIDs and H. pylori infection in dyspepsia remains unclear. Gastric adaptive relaxation may be related to the pathogenesis of functional dyspepsia because the response is often disturbed in dyspeptic patients. In this study, we investigated the effects of indomethacin or H. pylori water extracts on gastric adaptive relaxation. This experiment was performed using the modified method of Desai et al. Isolated guinea-pig stomach in an organ bath was monitored for intragastric pressure and volume. Adaptive relaxation was induced by gastric luminal distention. The effects of indomethacin and H. pylori on gastric relaxation were tested in this system. Indomethacin (> 1 x 10(-5) M) significantly inhibited adaptive relaxation. Indomethacin (> 3 x 10(-6) M) induced gastric relaxation in a dose-dependent fashion. However, aspirin at a concentration sufficient for cyclooxygenase (COX)-1 inhibition did not induce gastric relaxation. Preincubation with N-nitro-L-arginine methyl ester, a nitric oxide (NO)-synthase inhibitor, inhibited indomethacin-induced gastric relaxation. Adaptive relaxation was not affected by H. pylori water extracts. In conclusion, indomethacin inhibited adaptive relaxation via prior gastric relaxation. NO production, but not COX-1 inhibition, may be involved in this effect of indomethacin. H. pylori water extracts may not have direct effects on adaptive relaxation. Inhibition of adaptive relaxation may be one of the major mechanisms underlying NSAID-induced dyspepsia.     

"Points to consider" regarding safety assessment of biotechnology-derived pharmaceuticals in non-clinical studies (English translation)

Regulatory and industrial scientists collaborated to publish a "points to consider" document regarding the safety assessment of biotechnology-derived pharmaceuticals in non-clinical studies in 2002 (Pharmaceutical Non-clinical Investigation Group, 2002). The collaboration team intended to clarify the interpretation of ICH-S6 guideline and furthermore share recent Japanese practices on this matter. However, the document was written in Japanese. Thus, we share here an English translation of the document so that non-native Japanese correctly understand the contents.     

Vitrectomy with or without arteriovenous adventitial sheathotomy for macular edema associated with branch retinal vein occlusion

PURPOSE: compare the results of vitrectomy with or without arteriovenous (AV) crossing sheathotomy for macular edema associated with branch retinal vein occlusion (BRVO). DESIGN: Interventional case series. METHODS: A retrospective study of 36 eyes with BRVO-associated macular edema. Twenty eyes underwent AV sheathotomy (AS group), and 16 eyes underwent posterior vitreous detachment (PVD group). Best-corrected visual acuity (BCVA), fluorescein angiography (FA), and optical coherence tomography to determine foveal thickness were conducted preoperatively and at 12 months postoperatively. RESULTS: The mean postoperative BCVAs were significantly better in both the AS and the PVD group (P = .008 and P = .001, respectively). Foveal thickness decreased significantly 1 month after surgery in both groups (P = .002 and P = .007) and continued to decrease up to 12 months. The postoperative mean BCVA and improvement of BCVA and foveal thickness were not significantly different for the two groups at any postoperative period. Postoperative FA showed reperfusion of the occluded vein in 10 eyes in the AS group and 2 eyes in the PVD group, and formation of shunt vessels at the AV crossing site or around the macular region in all of the other eyes of both groups. CONCLUSIONS: Both AV sheathotomy and simple PVD significantly reduced macular edema associated with BRVO. However, there was no significant difference in the improvement of macular function following either procedure. Postoperative improvement of retinal circulation by either reperfusion of the occluded vein or collateral vessel formation was found. This accounted for functional and morphologic improvements.     

Comparison of the effects of latanoprost and timolol gel-forming solution on diurnal variation of intraocular pressure in normal-tension glaucoma

OBJECTIVE: To compare the effects of latanoprost (Lat) and timolol gel-forming solution (Tg) on the diurnal variation of intraocular pressure (IOP) in normal-tension glaucoma (NTG). SUBJECTS AND METHODS: A total of 47 NTG patients (47 eyes) were randomly assigned to receive Lat alone (25 eyes) or Tg alone (22 eyes). IOP was measured at fixed time points during 24 hours before and after treatment with each drug. In addition, blood pressure and pulse rate were measured before and after treatment. RESULTS: Lat reduced IOP significantly at all time points of measurement. Tg reduced IOP significantly at all time points of measurement except at 22:00 and 03:00. Percent reductions in the IOP at 03:00 and in the mean diurnal IOP were significantly greater in the Lat group than in the Tg group. In the Lat group there was no change in diastolic pressure or pulse rate after treatment, but in the Tg group these parameters decreased significantly. CONCLUSIONS: Comparison of diurnal variation of IOP before and after treatment shows that Lat is more effective than Tg in lowering IOP. In addition, Lat does not affect blood pressure or pulse rate.     

Increased excess deaths in urban areas: quantification of geographical variation in mortality in Japan, 1973-1998

To quantify the magnitude of geographical health inequality by sex and age group, and to observe the change in regional distribution of health disadvantage, this study estimated excess deaths attributable to the mortality variation among municipalities across Japan from 1973 through 1998. The municipalities (N = 3340 in 1995) were divided into quintiles according to standardized mortality ratio (SMR). Using the mortality of the lowest SMR quintile as the standard, the number of excess deaths (ED) and its ratio to observed deaths (EDR) were estimated by sex, age group (total population and under 65-year population) and regional block in 1973-1977, 1978-1982, 1983-1987, 1988-1992 and 1993-1998. Total annual ED in 1993-1998 was estimated as 47,124 for males and 46,562 for females, representing EDR of 9.9 and 11.6%, respectively. The under 65-year population had a higher EDR than the total population. Rural regions showed a marked decrease in EDR in contrast to the increase in urban regions over time. The present study suggests that the reduction of a large number of deaths, especially premature deaths, is expected by elimination of geographical health inequality, and that health policies for urban residents are prioritized.     

Influenza in Thailand: a case study for middle income countries

Recent studies in Hong Kong and Singapore suggest that the annual impact of influenza in these wealthy tropical cities may be substantial, but little is known about the burden in middle-income tropical countries. We reviewed the status of influenza surveillance, vaccination, research, and policy in Thailand as of January 2004. From 1993 to 2002, 64-91 cases of clinically diagnosed influenza were reported per 100,000 persons per year. Influenza viruses were isolated in 34% of 4305 specimens submitted to the national influenza laboratory. Vaccine distribution figures suggest that less than 1% of the population is immunized against influenza each year. In January 2004, Thailand reported its first documented outbreak of influenza A H5N1 infection in poultry and the country's first human cases of avian influenza. Thailand's growing economy, well-developed public health infrastructure, and effective national immunization program could enable the country to take more active steps towards influenza control.     

Effects of socioeconomic indicators on coronary risk factors, self-rated health and psychological well-being among urban Japanese civil servants

In Japan, the effects of socioeconomic indicators on coronary risk factors and subjective well-being in an urban population have not been compared. The subjects of this study were 1361 civil servants (968 men and 393 women, aged 35-64 years) working in an urban area of Japan. Screening examinations were conducted from April 1997 to March 1998, and a questionnaire survey was conducted in February 1998. The effects of two socioeconomic indicators, education level (junior high school, high school and university education) and employment grade (manual, low-level nonmanual and high-level nonmanual work), on behavioral and biological coronary risk factors, self-rated health and affect balance were investigated using multivariate logistic regression analyses. Smoking was found to be inversely associated with level of education; compared to university graduates, the odds ratios for subjects who had only graduated from high school and those for subjects who had only graduated from junior high school were 1.96 and 2.07 in men and 3.44 and 5.48 in women, respectively. As for alcohol drinking and physical inactivity, relationships were inconsistent in terms of direction by the two indicators. Among biological risk factors, diabetes was inversely associated with education level in men. Self-rated health, however, was inversely associated with employment grade both in men and women, and affect balance was inversely associated with employment grade in men. In summary, different effects of two socioeconomic indicators, education and employment grade, were seen in some coronary risk factors and subjective well-being in an urban Japanese population. Our findings should contribute to the elucidation of mechanisms of the socioeconomic gradients of risk factors and mortality from coronary heart disease in Japan.     

A tube-fed liquid formula diet containing dietary fiber increased stool weight in bed-ridden elderly patients

OBJECTIVE: The number of bedridden elderly patients who need a liquid diet has been increasing. We evaluated the usefulness of a tube-fed liquid diet containing cellulose and oligosaccharide for elderly bedridden patients. METHODS: Twenty-two elderly bedridden patients were given a liquid diet containing cellulose and lafinose for 4 wk. Parameters associated with blood and stool weight were measured during this period. RESULTS: Stool weight increased by 32.0 g in men and 8.8 g in women at 2 wk and remained at these weights up to 4 wk (P < 0.05 before and after 2 wk, 3 wk, and 4 wk in men, and P < 0.05 before and after 3 wk in women). Body weight increased in men (0.5 kg) and women (0.7 kg) 15 d after starting the diet and then remained at these values up to 29 d thereafter, and statistically significant differences were not seen. There were no changes in nutritional parameters such as total protein. CONCLUSION: No significant changes were observed in the general condition of elderly patients, with the exception of a positive increase in fecal weight, by 30-d supplementation of a liquid diet containing cellulose and lafinose.