Impact of walking upon medical care expenditure in Japan: the Ohsaki Cohort Study

BACKGROUND: Physical activity is expected to reduce medical costs by lowering the risk for a variety of chronic diseases. However, little is known about the actual magnitude of medical cost saved by physical activity. We attempted to quantify the association between time spent walking and medical care costs, based on a 4-year prospective observation of National Health Insurance (NHI) beneficiaries in rural Japan. METHODS: In 27 431 Japanese men and women, aged 40-79 years, who had no functional limitation or conditions interfering with physical activity at the baseline survey in 1994, we ascertained all hospitalizations, outpatient visits, and the costs through computerized linkage with NHI claims history files between January 1995 and December 1998. RESULTS: Medical costs significantly reduced with longer time spent walking. Per capita medical cost was pound 111.80 per month (95% CI: 109.3, 114.2) in those who walked for < or =30 minutes/day, pound 108.10 (95% CI: 105.7, 110.5) in those who walked for 30 minutes-1 hour, and pound 97.30 (95% CI: 95.5, 99.0) in those who walked for > or =1 hour, after multivariate adjustment of potential confounders. CONCLUSIONS: This prospective study in Japan indicated that time spent walking was significantly associated with lower medical costs.     

Effects of depletion of dihydropyrimidine dehydrogenase on focus formation and RPA phosphorylation

Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase (DPYD), partially inhibits homologous recombination (HR) repair and has a radiosensitizing effect as well as enhanced sensitivity to Camptothecin (CPT). DPYD is the target protein for radiosensitization by Gimeracil. We investigated the mechanisms of sensitization of radiation and CPT by DPYD inhibition using DLD-1 cells treated with siRNA for DPYD. We investigated the focus formation of various kinds of proteins involved in HR and examined the phosphorylation of RPA by irradiation using Western blot analysis. DPYD depletion by siRNA significantly restrained the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of NBS1. The numbers of colocalization of NBS1 and RPA foci in DPYD-depleted cells after radiation were significantly smaller than in the control cells. These results suggest that DPYD depletion is attributable to decreased single-stranded DNA generated by the Mre11/Rad50/NBS1 complex-dependent resection of DNA double-strand break ends. The phosphorylation of RPA by irradiation was partially suppressed in DPYD-depleted cells, suggesting that DPYD depletion may partially inhibit DNA repair with HR by suppressing phosphorylation of RPA. DPYD depletion showed a radiosensitizing effect as well as enhanced sensitivity to CPT. The radiosensitizing effect of DPYD depletion plus CPT was the additive effect of DPYD depletion and CPT. DPYD depletion did not have a cell-killing effect, suggesting that DPYD depletion may not be so toxic. Considering these results, the combination of CPT and drugs that inhibit DPYD may prove useful for radiotherapy as a method of radiosensitization.     

Hypereosinophilic syndrome complicated by myelofibrosis]

Hypereosinophilic syndrome (HES) with myelofibrosis was diagnosed in a 36-year-old man on the basis of bone marrow biopsy findings and clinical features. Although the patient was treated with steroid (1 mg/kg), hydroxyurea, and immunosuppressive therapy, eosinophilia persisted. Patients with HES and myelofibrosis are usually unresponsive to antineoplastic agents and/or immunosuppressants. However, cyclosporin may be an effective alternative for such patients.     

Screening for gastric cancer

Mass screening for gastric cancer in Japan has been conducted nationwide since 1960. The total number of examinees in 1985 amounted to 5,161,876 and 6,240 cases (0.12%) of gastric cancer were detected. Approximately half of these cases were early stage cancers. According to the studies of mass gastric screening in the Miyagi Prefecture, Japan, the sensitivity of the screening test by the indirect x-ray method was 82.4%, and the specificity was 77.2%. The positive predictive value was 1.78%. Recently, mortality from gastric cancer has been decreasing in Japan. Many studies have been carried out to investigate the relationship between the decreasing trend of mortality from cancer of the stomach and the effectiveness of mass gastric screening. From these studies and from time trend analyses of incidence and death rates, case-control studies, nonexperimental cohort studies, etc., it is believed that mass screening for gastric cancer is effective in reducing the death rate from cancer at this site.

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Resumen El tamizaje masivo para cáncer gástrico a nivel nacional ha sido realizado en el Japon desde 1960. El núméro total de personas examinadas en 1985 ascendió a 5,161,876 y se detectaron 6,240 (0.12%) cánceres gástricos. Aproximadamente la mitad de estos casos fueron cánceres en estadio temprano. Según los estudios de tamizaje gástrico masivo en la Prefectura Miyagi, Japón, la sensibilidad de la prueba de tamizaje mediante el método indirecto de rayos x es 82.4%, y la especificidad, 77.2%. El valor de predicción positiva es 1.78%. Recientemente, la tasa de mortalidad del cáncer gástrico ha venido disminuyendo. Muchos estudios han sido realizados para investigar la relación entre la decreciente tendencia de la mortalidad por cáncer del estómago y la efectividad del tamizaje gástrico masivo. Los resultados de tales estudios, así como los análisis de incidencia cronológica, los estudios sobre casos controlados, y sobre cohortes no expérimentales, etc., permiten afirmar que el tamizaje masivo para cáncer gástrico es efectivo en cuanto a la reducción de tasa de mortalidad del cáncer de estómago.

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Résumé Le dépistage national pour le cancer gastrique est établi au Japon depuis 1960. Le nombre de patients examinés en 1985 était 5,161,876; 6,240 (0.12%) cas de cancer gastrique ont été détectés. La moitié environ de ces cas étaient des cancers à un stade précoce. Selon les chiffres de la Préfecture de Miyagi, la sensibilité du dépistage par la radioscopie mobile était de 82.4%, la spécificité de 77.2%, et la valeur prédictive positive de 1.78%. Plus récemment, la mortalité due au cancer gastrique était en régression au Japon. Bien des études ont été consacrées à l'efficacité du dépistage de masse dans l'abaissement du taux de mortalité du cancer. De ces résultats et d'après les analyses actuarielles de l'incidence et de la mortalité, les études rétrospectives comparant les groupes atteints de cancer et ceux qui restent indemnes, les études non expérimentales de groupes et autres, on a conclu que le dépistage de masse est efficace pour réduire la mortalité du cancer gastrique.

     

RETROSPECTIVE COHORT STUDY OF CHRONOLOGICAL CHANGE OF SHORT‐SEGMENT BARRETT's ESOPHAGUS

Background: The natural history of short‐segment Barrett's esophagus (SSBE) is not fully understood. We, thereby, conducted a retrospective cohort study to provide further information about chronological change of SSBE. Materials and methods: A total of 174 cases undergoing upper gastrointestinal endoscopy from April 1980 to October 2002 were diagnosed to have SSBE based on the definition of Barrett's esophagus proposed by the Japanese Society for Esophageal Diseases. A cohort of 100 patients with SSBE less than 3 cm was enrolled in the present study. The mean follow‐up period was 76.2 ± 59.9 months and 4.27 ± 2.66 endoscopic examinations were performed on each patient. The cumulative probability of elongation of SSBE to 3 cm or longer was estimated by the Kaplan‐Meier method. Then, independent contributing factors to its elongation were determined using Cox's proportional hazard model. Results: Elongation of SSBE to 3 cm or longer occurred in 30 patients (30%) during the follow‐up period. The cumulative 5‐year probability of elongation of SSBE to 3 cm or longer was 18.4%. Hiatal hernia, severe reflux esophagitis and SSBE 1 cm or longer at initial diagnosis were proven to be independent contributing factors to its elongation. Conclusions: The present study demonstrated that SSBE has a tendency to increase its length over time especially when it is accompanied by hiatal hernia or by severe reflux esophagitis.     

Determination of lipophilicity of two quinolone antibacterials, ciprofloxacin and grepafloxacin, in the protonation equilibrium.

The objective of this study was to compare protonation equilibrium and lipophilicity of two quinolone antibacterials, grepafloxacin (GPFX) and ciprofloxacin (CPFX), in order to give an insight into effects on the physicochemical properties by slight structural motifs. The protonation equilibrium was investigated by a spectrophotometry. Macro- and micro-dissociation constants were simultaneously determined, based on nonlinear regression analysis using the MULTI program, and then microspecies distribution could be described accordingly. Zwitterionic microspecies predominated at isoelectrical point (pI) for both drugs, and the concentration ratio of neutral to zwitterionic forms was near 4-fold greater for GPFX than that for CPFX. The apparent partition coefficient (D(O/B,pH)) versus pH profiles had the shape of a parabolic curve in an n-octanol/buffer system, and reached the maximum around pI for both, respectively. Moreover, two introduced methyl groups in GPFX increased not only intrinsic lipophilicity but also neutral microspecies fraction relative to CPFX, and D(O/B,pH) of GPFX was consequently far higher than that of CPFX. The results emphasized that there were significant differences in protonation equilibrium and lipophilicity between GPFX and CPFX, which conduced to explaining their different behavior in terms of antibacterial activities and pharmacokinetics.     

Effectiveness of etoposide on reactive histiocytosis and refractory state to platelet transfusion during therapy of leukemia: case report

The patient is 11-year-old girl who was diagnosed as having hybrid acute leukemia (myeloid and lymphoid) from morphological (cytochemistry) findings, immunophenotype and genotype. During reinduction therapy after a second relapse, she presented hepatosplenomegaly and the remittent fever unresponsive to the intensified antibiotics. The diagnosis of reactive histiocytosis was made because of the remarkable elevation of serum ferritin value and proliferation of mature histiocytes in the bone marrow. Treatment with etoposide resulted in the disappearance of her fever and other symptoms. The subsequent refractoriness to platelet transfusion was also overcome by etoposide (p.o.) therapy. The results suggested that the treatment with etoposide might be effective for reactive histiocytosis and the related refractory state to platelet transfusion during therapy for leukemia.     

A side effect of neuraminidase inhibitor in a patient with liver cirrhosis

Neuraminidase inhibitors have been widely used in Japan since 2001, and several side-effects of their use have been reported. However, erythema toxicum has rarely been described as a side-effect of these drugs in patients with liver function disorder. Here, we report a case of generalized rash after treatment with the neuraminidase inhibitors zanamivir and oseltamivir administered prophylactically to prevent influenza infection in two patients with hepatoma associated with liver cirrhosis.