Osamu Tokumaru

Sex- and age-related differences in morbidity rates of 2009 pandemic influenza A H1N1 virus of swine origin in Japan.

Background The objective of the present study was to determine whether the morbidity rates of the 2009 pandemic influenza A H1N1 virus (pdmH1N1) varied by age and/or sex. Methods and Findings Retrospective analysis of 2,024,367 cases of pdmH1N1 was performed using the national surveillance data from influenza sentinel points in Japan. The male-to-female morbidity ratios (M/F ratios) in nineteen age groups were estimated as the primary outcome. The M/F ratios for pdmH1N1 influenza were: >1 in age groups <20 years and ≥80 years (p<0.001); <1 in age groups 20–79 years (p<0.001). This data suggests that males <20 years of age may be more likely to suffer from pdmH1N1 influenza than females in the same age categories. When the infection pattern for pdmH1N1was compared with that of seasonal influenza outbreaks between 2000 and 2008, the M/F ratio for pdmH1N1 influenza was higher in ages 3–29 years and lower in ages 40–79 years. Because the present study was based on the national surveillance, it was impossible to estimate the morbidity rate for the Japanese population. It is also likely that the data did not capture asymptomatic or mild infections. Conclusions Although exposure to the pdmH1N1 virus is assumed to be similar in both boys and girls, M/F ratios were >1 in those younger than 20 years. The subsequent reversal of the M/F ratio in the adult generation could be due to several possibilities, including: greater immunity among adult males, more asymptomatic infections among males, less reporting of illness by males, or differences in exposure to the virus and probability of visiting a clinic. These results suggest that the infection and virulence patterns of pdmH1N1 are more complex than previously considered.

Age-Specific Sex-Related Differences in Infections: A Statistical Analysis of National Surveillance Data in Japan

Background To prevent and control infectious diseases, it is important to understand how sex and age influence morbidity rates, but consistent clear descriptions of differences in the reported incidence of infectious diseases in terms of sex and age are sparse. Methods and Findings Data from the Japanese surveillance system for infectious diseases from 2000 to 2009 were used in the analysis of seven viral and four bacterial infectious diseases with relatively large impact on the Japanese community. The male-to-female morbidity (MFM) ratios in different age groups were estimated to compare incidence rates of symptomatic reported infection between the sexes at different ages. MFM ratios were >1 for five viral infections out of seven in childhood, i.e. male children were more frequently reported as infected than females with pharyngoconjunctival fever, herpangina, hand-foot-and-mouth disease, mumps, and varicella. More males were also reported to be infected with erythema infectiosum and exanthema subitum, but only in children 1 year of age. By contrast, in adulthood the MFM ratios decreased to <1 for all of the viral infections above except varicella, i.e. adult women were more frequently reported to be infected than men. Sex- and age-related differences in reported morbidity were also documented for bacterial infections. Reported morbidity for enterohemorrhagic Escherichia coli infection was higher in adult females and females were reportedly more infected with mycoplasma pneumonia than males in all age groups up to 70 years. Conclusions Sex-related differences in reported morbidity for viral and bacterial infections were documented among different age groups. Changes in MFM ratios with age may reflect differences between the sexes in underlying development processes, including those affecting the immune, endocrine, and reproductive systems, or differences in reporting rates.

Gamma knife surgery of the pituitary: new treatment for thalamic pain syndrome

OBJECT Although reports in the literature indicate that thalamic pain syndrome can be controlled with chemical hypophysectomy, this procedure is associated with transient diabetes insipidus. It was considered reasonable to attempt gamma knife surgery (GKS) to the pituitary gland to control thalamic pain. METHODS Inclusion criteria in this study were poststroke thalamic pain, failure of all other treatments, intolerance to general anesthetic, and the main complaint of pain and not numbness. Seventeen patients met these criteria and were treated with GKS to the pituitary. The target was the pituitary gland together with the border between the pituitary stalk and the gland. The maximum dose was 140 to 180 Gy. All patients were followed for more than 3 months. CONCLUSIONS An initial significant pain reduction was observed in 13 (76.5%) of 17 patients. Some patients experienced pain reduction within 48 hours of treatment. Persistent pain relief for more than 1 year was observed in five (38.5%) of 13 patients. Rapid recurrence of pain in fewer than 3 months was observed in four (30.8%) of 13 patients. The only complication was transient diabetes insipidus in one patient. It would seem that GKS of the pituitary might have a role to play in thalamic pain arising after a stroke.

The effect of gamma knife irradiation on functions of striatum in rats

OBJECT An animal model has been developed to study the effect of gamma knife surgery(GKS) on cerebral function. METHODS A rat was fixed in a newly developed Régis-Valliccioni frame that enables the target region to be planned directly on the magnetic resonance images. The left striatum was irradiated with 150 Gy via a 4-mm collimator of the Leksell gamma knife. Apomorphine (dopamine agonist) was administered to elicit a circling behavior (apomorphine test) after the GKS so as to examine the time course of the changes in dopaminergic functions of irradiated striatum. After a series of behavioral analyses, irradiated brains were subjected to histological examination. Necrosis was observed in the irradiated area surrounded by hemorrhage and gliosis. The distance between the histologically estimated and planned centers of the irradiation areas was 1.0 ± 0.5 mm. The extent of the distance was due to errors along dorsoventral axis. The distribution of the irradiation areas influenced the activity and the circling behaviors in apomorphine test, which was suggestive of involvement of the nigrostriatal pathway. CONCLUSIONS Targeting by using the Régis-Valliccioni frame was very accurate compared with targeting with coordinates based on brain maps used hitherto. Although targeting improved the accuracy, further effort will still be necessary to reduce errors along dorsoventral axis. The apomorphine test indicated a reduced dopaminergic function of the irradiated area including striatum, which accompanied histological changes after a high dose of irradiation (150 Gy).

Gamma Knife Radiosurgery Targeting Protocols for the Experiments with Small Animals

Background/Aims: Manipulation of brain functions via Gamma Knife (GK) irradiation would have numerous applications in clinical and experimental neurology. Methods: Alteration of brain functions in the unilaterally irradiated striatum was indexed through monitoring freely moving rat behaviors. Spontaneous activity and rotations on the apomorphine test, which can detect dopaminergic function imbalance, were indexed employing our behavior tracking system. The spatial distribution of necrotic lesions was explored using serial sections, and was assumed to represent the real foci of the GK target. Results: Distinct behavioral alterations corresponded to the precise locations of the lesions in various areas of the basal ganglia. Displacement of the irradiation sites in the anteromedial direction increased spontaneous activity, and posterolateral shift provoked circling behavior on the apomorphine test. Conclusion: Accurate positioning of the target is crucial for experimental GK irradiation locally focused on domains of a small brain such as that of the rat. Here, we propose a protocol for converting the ‘intended’ focus, based on brain map coordinates, to a ‘planned’ focus on the MR imaging coordinate system with the Régis-Valliccioni stereotactic frame.

Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used for preventing cardiovascular and cerebrovascular diseases by controlling blood cholesterol level. Additionally, previous studies revealed the scavenging effects of statins on free radicals. We assessed direct scavenging activities of two water-soluble statins, fluvastatin and pravastatin, on multiple free radicals using electron spin resonance spectrometry with spin trapping method. We estimated reaction rate constants (kfv for fluvastatin, and kpv for pravastatin). Superoxide anion was scavenged by fluvastatin and pravastatin with kfv and kpv of 4.82 M−1s−1 and 49.0 M−1s−1, respectively. Scavenging effects of fluvastatin and pravastatin on hydroxyl radical were comparable; both kfv and kpv were >109 M−1s−1. Fluvastatin also eliminated tert-butyl peroxyl radical with relative kfv of 2.63 to that of CYPMPO, whereas pravastatin did not affect tert-butyl peroxyl radical. Nitric oxide was scavenged by fluvastatin and pravastatin with kfv and kpv of 68.6 M−1s−1 and 701 M−1s−1, respectively. Both fluvastatin and pravastatin had scavenging effects on superoxide anion, hydroxyl radical and nitric oxide radical. On the other hand, tert-butyl peroxyl radical was scavenged only by fluvastatin, suggesting that fluvastatin might have more potential effect than pravastatin to prevent atherosclerosis and ischemia/reperfusion injury via inhibiting oxidation of lipids.

Neuroprotective effects of ethyl pyruvate on brain energy metabolism after ischemia depend on glial cells: A 31P-NMR study

Neuroprotective effects of ethyl pyruvate (EP), a stable derivative of pyruvate, on energy metabolism of rat brain exposed to ischemia were investigated by 31P-nuclear magnetic resonance (31P-NMR) spectroscopy.Brain slices (400 m) were incubated in standard artificial cerebrospinal fluid (ACSF) with 2 mM EP (EP+) or ACSF only (EP-) at 25 ◦C. Brain slices were exposed to ischemia by halting the perfusion for 1 h. Levels of high-energy phosphates, phosphocreatine (PCr) and -ATP, relative to pre-ischemic levels were measured by 31P-NMR.Recovery of PCr after reperfusion was significantly greater in EP+ than in EP−. When brain slices were pretreated with 100 M fluorocitrate, an astrocytic poison, such difference in recovery of PCr was not observed. These results indicated that neuroprotective effects of EP depend on the presence of astrocytes. EP might be neuroprotective via functions of astrocytes as a neuro-protectant from oxidative stress and/or a provider of lactate by glycolysis.