Phase III randomised controlled trial of neoadjuvant chemotherapy plus radical surgery vs radical surgery alone for stages IB2, IIA2, and IIB cervical cancer: a Japan Clinical Oncology Group trial (JCOG 0102).

BACKGROUND: A phase III trial was conducted to determine whether neoadjuvant chemotherapy (NACT) before radical surgery (RS) improves overall survival. METHODS: Patients with stage IB2, IIA2, or IIB squamous cell carcinoma of the uterine cervix were randomly assigned to receive either BOMP (bleomycin 7 mg days 1-5, vincristine 0.7 mg m(-2) day 5, mitomycin 7 mg m(-2) day 5, cisplatin 14 mg m(-2) days 1-5, every 3 weeks for 2 to 4 cycles) plus RS (NACT group) or RS alone (RS group). Patients with pathological high-risk factors received postoperative radiotherapy (RT). The primary end point was overall survival. RESULTS: A total of 134 patients were randomly assigned to treatment. This study was prematurely terminated at the first planned interim analysis because overall survival in the NACT group was inferior to that in the RS group. Patients who received postoperative RT were significantly lower in the NACT group (58%) than in the RS group (80%; P=0.015). The 5-year overall survival was 70.0% in the NACT group and 74.4% in the RS group (P=0.85). CONCLUSION: Neoadjuvant chemotherapy with BOMP regimen before RS did not improve overall survival, but reduced the number of patients who received postoperative RT.

Safety and efficacy of a splenectomy during debulking surgery for Müllerian carcinoma.

PURPOSE: This study was designed to assess the safety and efficacy of a splenectomy and to analyze the prognostic factors of Müllerian carcinoma with spleen metastasis. METHODS: We reviewed the medical records of 11 patients with Müllerian carcinoma who underwent a splenectomy between 1997 and 2007. The treatment outcome of these patients was examined and the possible prognostic factors were investigated by univariate analysis. RESULTS: Four and seven patients underwent a splenectomy for primary and recurrent disease, respectively. A complete resection was achieved in eight patients. A blood transfusion was not required and only two mild postoperative complications were observed. The median and five-year survivals of all patients following treatment were 39 months and 39%, respectively. Older patients (> or = 60 years old) and patients with a poor performance status (PS2) had a poorer prognosis by univariate analysis. CONCLUSIONS: A splenectomy can be performed safely and effectively during debulking surgery for appropriately selected patients with primary or recurrent Müllerian carcinoma.

Radical hysterectomy for FIGO stage I-IIB adenocarcinoma of the uterine cervix.

A retrospective analysis was carried out to identify risk factors for survival and relapse in patients with FIGO stage I-IIB cervical adenocarcinoma (AC), who underwent radical hysterectomy, and to compare outcome and spread pattern with those of squamous cell carcinoma (SCC). One hundred and twenty-three FIGO stage I-IIB patients with AC and 455 patients with SCC, who all underwent primary radical hysterectomy, were reviewed. Among the patients with AC, Cox model identified tumour size (95% CI: 1.35-30.71) and node metastasis (95% CI: 5.09-53.44) as independent prognostic factors for survival, and infiltration to vagina (95% CI: 1.15-5.76) and node metastasis (95% CI: 6.39-58.87) as independent prognostic factors for relapse. No significant difference was found in survival or relapse between the AC and SCC groups, after adjusting for other clinicopathological characteristics using Cox model. No significant difference was found in the positive rates of lymph nodes or location of initial failure sites between the two groups, but ovarian metastatic rate was significantly higher in patients with pathologic stage IIB AC (P=0.02). Positive node is a common independent prognostic factor for survival and relapse of patients with AC. FIGO stage I-IIB patients with AC or SCC, who underwent radical hysterectomy, have similar prognosis and spread pattern, but different ovarian metastasis rates.

Vitamin D deficiency in patients with active systemic lupus erythematosus.

UNLABELLED: We investigated the effects of disease activity on bone metabolism in 36 patients with systemic lupus erythematosus (SLE). Changes in bone remodeling were not explained by corticosteroid use. A high prevalence of 25OHD deficiency in SLE patients indicates the need for vitamin D replacement, mainly during high disease activity periods. INTRODUCTION: We investigated the effects of SLE disease activity on bone metabolism, their relation to inflammatory cytokines and vitamin D levels. METHODS: We performed a cross-sectional analysis of 36 SLE patients classified according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in high activity (group I: 12 patients, mean age 29.6 years) or in minimal activity (group II: 24 patients, mean age 30.0 years), and compared them to normal controls (group III: 26 women, 32.8 years). Serum calcium, phosphorus, parathyroid and sex hormones, bone remodeling markers, interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), IL-1, tumor necrosis factor-alpha (TNF), 25-hydroxivitamin D (25OHD), and 1,25-dihydroxyvitamin D3 were measured, plus bone mineral density. RESULTS: All cytokines were significantly higher in SLE groups; IL-6 could differentiate SLE patients from controls. In group I, 25OHD levels were lower (P < 0.05), which was related to the SLEDAI (R = -0.65, P < 0.001). In multiple regression analysis, the 25OHD level was associated with SLEDAI, osteocalcin and bone-specific alkaline phosphatase. The SLEDAI score was positively correlated with all measured cytokines and especially TNF (R = 0.75, P < 0.001). CONCLUSIONS: SLE patients demonstrated changes in bone remodeling strongly related to disease activity. A high prevalence of 25OHD deficiency was observed in SLE patients, indicating the need for vitamin D replacement.

Depletion of brain catecholamines: failure of ocular dominance shift after monocular occlusion in kittens.

Monocularly deprived kittens were compared with littermates that had had their eyelids sutured for the same time but that had, in addition, been treated with 6-hydroxydopamine to deplete their forebrains of catecholamines. The visual cortices of all the catecholamine-depleted kittens showed high proportions of binocular neurons, in contrast to the control group, most of whose visual cortical neurons were driven exclusively by the nondeprived eye. Catecholamines may play an important role in the maintenance of cortical plasticity during the critical period.

Genotoxicity studies on green tea catechin.

The beneficial effects of tea catechins are well documented. We evaluated the genotoxic potential of a green tea catechin preparation using established genotoxicity assays, including a bacterial reverse mutation assay (Ames test), a chromosomal aberration assay in cultured Chinese hamster lung cells (CHL/IU), a mouse lymphoma L5178Y/tk assay, and a bone marrow micronucleus (MN) assay in ICR CD mice and SD rats. No significant increases in the number of revertant colonies were observed in the Ames test, but positive responses were observed in two in vitro assays: the chromosomal aberration assay and mouse lymphoma L5178/tk assay. However, the in vivo study demonstrated no significant increase in micronucleated polychromatic erythrocytes (MNPCE) in the bone marrow of both ICR CD mice and SD rats administered a high dose of the green tea catechin preparation up to 2000mg/kg. Combined with favorable epidemiological information suggesting a chemopreventive effect of tea catechins on carcinogenesis, we conclude that green tea catechin presents no significant genotoxic concern under the anticipated conditions of use. These results are consistent with other genotoxicity studies of tea catechins, which show minimal, if any, genotoxic potential.

Neural plasticity maintained high by activation of cyclic AMP-dependent protein kinase: an age-independent, general mechanism in cat striate cortex.

Adult cats lack ocular dominance plasticity, showing little change in the ocular dominance distribution following monocular deprivation. Ocular dominance plasticity is also lost in kitten visual cortex that has been continuously infused with either catecholaminergic neurotoxin, beta-adrenoreceptor blocker, or inhibitor of cyclic AMP-dependent protein kinase (protein kinase A). Complementarily, in adult cats we showed earlier that pharmacological activation of protein kinase A, albeit partially, restored ocular dominance plasticity. In the present study, we first asked whether, mediated by protein kinase A activation, the same molecular mechanisms could restore ocular dominance plasticity to kitten cortex that once lost the expression of plasticity due to prior pharmacological treatments. Concurrently with monocular deprivation, two kinds of cyclic AMP-related drugs (cholera toxin A-subunit or dibutyryl cyclic AMP) were directly infused in two types of aplastic kitten cortex pretreated with either 6-hydroxydopamine or propranolol. The combined treatment resulted in clear ocular dominance shift to the non-deprived eye, indicating that cortical plasticity was fully restored to aplastic kitten cortex. Next, to directly prove the sensitivity difference in protein kinase A activation between the immature and mature cortex, we compared the thus-obtained data in kittens with the published data derived from adult cats under the comparable experimental paradigm. The extent of ocular dominance changes following monocular deprivation was compared at different drug concentrations in the two preparations: the shifted ocular dominance distribution in aplastic kitten cortex infused with dibutyryl cyclic AMP at the lowest concentration tested and the W-shaped distribution in similarly treated adult cortex at a thousandfold-higher drug concentration that induced nearly maximal changes. We conclude that, irrespective of the animal's age, activation of protein kinase A cascades is a general mechanism to maintain ocular dominance plasticity high, their sensitivity being substantially higher in the immature than mature cortex.

Surgical treatment for neuroendocrine carcinoma of the uterine cervix.

OBJECTIVE: To identify the best operative approach for neuroendocrine cervical carcinoma (NECC). METHODS: The records of surgically treated patients with stages IB to IIB NECC were reviewed. RESULTS: Of 10 patients who met the study criteria for NECC and underwent radical hysterectomy, 4 had pT1bN0, 4 had pT1bN1, 1 had pT2aN0, and 1 had pT2bN1 disease. Those with pT1bN1 or pT2bN1 disease received postoperative adjuvant radiotherapy and/or chemotherapy, and recurrence occurred in 7 patients (70%). Among these 7 patients, 5 (71%) had a primary NECC tumor with deep stromal invasion and 5 (71%) had extrauterine disease (parametrium and/or lymph node). The recurrences in 6 patients (86%) were located outside the pelvis (lung, liver, or brain). Stromal invasion was 6 mm or less in the 3 patients who did not experience disease recurrence. CONCLUSIONS: Pelvic control by radical hysterectomy may not be beneficial for patients with NECC except for those with an early invasive lesion.

Genotoxicity studies on dietary diacylglycerol (DAG) oil.

Dietary diacylglycerol (DAG) oil is an edible oil enriched in DAG (more than 80%). A recent investigation indicated that DAG oil or its components may have beneficial effects on the prevention and management of obesity. We evaluated the genotoxic potential of DAG oil using standard genotoxicity tests. Bacterial reverse mutation assay (Ames test), the chromosomal aberration assay in cultured Chinese hamster lung cells (CHL/IU), and a bone marrow micronucleus assay in ICR CD mice were employed in the present study. In addition we have tested the possibility that genotoxic substances may be formed during cooking, heated DAG oil (HDG) was prepared by batch frying potato slices in the oil at 180 degrees C for 8 h/day for three consecutive days. Therefore, genotoxicity tests were also performed on HDG. Results obtained did not show any genotoxic effect on either unheated DAG oil (UDG) or HDG. We conclude that there are no safety concerns on the genotoxicity of DAG oil under the conditions for normal use.

Clinical aspects and prognosis of pelvic recurrence of cervical carcinoma.

OBJECTIVE: To identify which patients with locally recurrent cervical carcinoma are potentially curable. METHOD: A total of 664 stage IB-IVA patients were examined following surgery or radiotherapy. RESULT: Among the 664 patients, 193 (29%) developed recurrence. Sixty-seven (35%) of these recurrences were located in the pelvis alone. Among these 67 recurrences, 24 (35%) were central recurrences and the remaining 43 (65%) were pelvic side-wall recurrences. Of the 24 patients with central recurrences, 8 were salvaged. Of these 8 patients, 3 underwent pelvic exenteration, and 5 received optimal radiotherapy. The recurrent tumor in these 5 survivors who received radiotherapy had consisted of a small (<2 cm) tumor. All 43 patients with pelvic wall recurrence developed progressive disease. CONCLUSION: The following patients are potentially curable: patients with a resectable, centrally located tumor who are candidates for pelvic exenteration, and patients with a small central recurrence for whom complete radiation therapy is feasible.

Continuous hepatocyte growth factor supply prevents lipopolysaccharide-induced liver injury in rats.

We present a rat model in which continuous supply of hepatocyte growth factor (HGF) prevents liver injury induced by carbon tetrachloride (CCl4) and E. coli 011:B4 lipopolysaccharide (LPS). Rat fibroblasts genetically modified to secrete rat HGF were implanted in syngenic rat spleen 7 days before administration of the hepatotoxins. Rats with HGF-secreting fibroblasts in the spleen showed a dramatic resistance to CCl4- and LPS-induced liver injury. In the LPS-induced liver injury model, blood chemical analysis revealed that the increase in serum glutamic oxalacetic transaminase level and the decrease in blood sugar level were remarkably suppressed in rats with HGF-secreting cells in the spleen. Most importantly, their survival rate was greatly improved compared to other control groups of rats. Thus our results indicate a new role of HGF in liver protection during endotoxemia and convey important clinical implications for developing new therapeutic modalities in the treatment of liver failure caused by endotoxemia.

Preservation of binocularity after monocular deprivation in the striate cortex of kittens treated with 6-hydroxydopamine.

The results of single unit recordings from Area 17 of monocularly deprived kittens were compared with similar ones from littermates who had been monocularly lid-sutured for the same period of time, but who had in addition been given intraventricular injections of 6-hydroxydopamine (6-OHDA) to deplete brain catecholamines. This visual cortices of all catecholamine-depleted kittens showed high proportions of binocular neurons, in contrast to the control group, a majority of whose visual cortical neurons were driven exclusively by the non-deprived eye. Preservation of binocularity in 6-OHDA-treated kittens was dose-related. Even after a 1 to 2-week period of lidsuture which reduced binocularity to 20% in controls, normal proportions of binocular neurons (greater than 75%) were preserved if the cumulative dose had been 10 mg 6-OHDA or more. The density of single neurons sampled from electrode tracks through the cortex of drug-treated kittens was high and did not differ significantly from controls. Neurons were isolated every 100 micron on the average. There was some indication that the drug's effect in preventing an ocular dominance shift disappears by six weeks following cessation of 6-OHDA treatment. This reversal of the physiological effects in cortex is preceded by recovery from the behavioral manifestations of 6-OHDA treatments. Binocularity was only slightly increased in a kitten who received large doses of 6-OHDA after a period of monocular deprivation. This observation, together with control recordings from normal kittens and adults treated with 6-OHDA, indicates that the direct effects of 6-OHDA on cortical neurons' response properties play a minor role in comparison to its effects in reducing the sensitivity of the cortex to monocular deprivation. The overwhelming majority of cortical neurons in 6-OHDA-treated kittens remained normal in receptive field properties after a period of monocular deprivation. These data support the hypothesis that catecholamines are required for the maintenance of visual cortical plasticity during the critical period.

Restoration of visual cortical plasticity by local microperfusion of norepinephrine.

Using a newly developed technique of continuous microperfusion, we obtained further evidence in support of our hypothesis that the neocortical catecholamines (CAs), particularly norepinephrine (NE), are responsible for a high level of cortical plasticity. We used the visual cortical changes in ocular dominance which follow a brief monocular deprivation as a simple and reliable index of cortical plasticity. Local perfusion of kitten visual cortex with 1 mg/ml (4.0 mM) 6-hydroxydopamine (6-OHDA) prevented the effects of monocular deprivation in kittens, thus replicating the results we had obtained using intraventricular injections (Kasamatsu and Pettigrew, '76b, '79). Locally perfused NE at a concentration of of 10(-2) mg/ml (48.6 micron) restored visual cortical plasticity in animals which were no longer susceptible to brief monocular lid-suture. These numbers refer to the concentration of solutions in the cannula/minipump system. The effective concentrations at the site of recording (about 2 mm away) are probably much lower than these. This effect of NE perfusion was seen both in kittens which had received prior 6-OHDA treatment as well as in older animals which had outgrown the susceptible period. In the kittens we obtained as a nearly complete shift in ocular dominance toward the open eye and in the older animals a decrease in binocularity was obtained. The changes were found only in the local region of visual cortex perfused with either NE or 6-OHDA, while nearby cortical regions in the same animals were unaffected. There were no obvious changes in receptive field properties of individual neurons other than ocularity, and externally perfused NE did not itself reduce binocularity in normal animals: the effects of NE described about only occurred when the animal's visual experience was simultaneously altered. These results support the view that NE plays an important role in cortical plasticity.

Clinical experience of fast neutron therapy for carcinoma of the uterine cervix.

Fast neutron therapy for locally advanced or radioresistant malignant tumors was started in November 1975 at the National Institute of Radiological Sciences (NIRS), Chiba, Japan. To evaluate the effectiveness of fast neutron therapy, mixed neutron-photon fractionated irradiation, on squamous cell carcinoma of the uterine cervix, 98 patients with Stage IIIb disease were examined to study the correlation between local control rate and histological types. The local control rate after neutron-mixed beam therapy was 73%, which decreased to 66% with photon irradiation. The five year survival rate was 49% for patients receiving neutron therapy and 49% for those receiving photon therapy. There was no statistical significance between neutron and photon therapy; we then attempted to analyze histological types to check for any gain using neutron therapy. This study was a nonrandomized trial. The preliminary results however, gave us useful information for the next of neutron therapy.

Concentration-dependent suppression by beta-adrenergic antagonists of the shift in ocular dominance following monocular deprivation in kitten visual cortex.

We showed that beta-adrenergic receptor antagonists blocked the shift in ocular dominance following brief monocular deprivation in young kittens. Localized microperfusion of propranolol into the kitten visual cortex reduced the expected shift in the ocular dominance approximately 2 mm away from the center of perfusion. The blocking effect, however, did not reach an area approximately 5 mm from the perfusion center, suggesting that beta blockers work in a concentration-dependent fashion in the present paradigm. We further studied the concentration-effect relationship by widely changing the concentration of beta blockers (propranolol and sotalol) stored in an osmotic minipump. The proportion of binocular cells increased from 0.13 to 0.67 when the concentration of propranolol was increased from 10(-6)M to 10(-2)M, giving the half-maximum effect (binocularity, 0.40) at about 10(-4)M propranolol. However, the maximum binocularity obtained with the sotalol perfusion under the comparable condition was apparently much lower (0.45) than that with propranolol. Accordingly, the half-maximum binocularity (0.30) was obtained at about 10(-5)M sotalol. We also noted the presence of a linear, inverse relation between the logarithmic concentration of the beta blockers and the extent of the shift in ocular dominance as measured by the proportion of monocular cells which responded exclusively to stimulation of the nondeprived eye. The latter decreased from 0.75 to 0.25, when the former was increased from 10(-6)M to 10(-2)M (in an osmotic minipump). The two beta blockers behaved similarly in this correlation. The intracortical spread of locally perfused [3H]propranolol was studied at the end of the cortical perfusion which lasted for a week. The radioactivity was highest at the perfusion center and rapidly declined with increasing distance, leveling off approximately 3 mm from the perfusion center. The average "dilution factor" of locally perfused [3H]propranolol was calculated as about 1/170 of the original solution in an area of physiological recordings (approximately 2 mm from the perfusion center). Applying the "dilution factor" of 1/170, we estimated the approximate concentration of beta blockers needed at the recording sites to obtain the half-maximum effect; it was about 5.8 X 10(-8)M for sotalol. Taken together, the present results were interpreted as suggesting that there is a positive correlation between the number of activated beta-adrenergic receptors within the visual cortex and the extent of changes in ocular dominance following monocular deprivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Roles of N-methyl-D-aspartate receptors in ocular dominance plasticity in developing visual cortex: re-evaluation.

We have re-examined whether N-methyl-D-aspartate receptors play a specific role in experience-dependent plasticity in kitten visual cortex. A specific antagonist of this glutamate receptor subtype, D,L-2-amino-5-phosphonovaleric acid, was directly and continuously infused into kitten striate cortex for one week concurrently with monocular lid suture. In the hemisphere infused with 50 mM antagonist, we found the usual shift in ocular dominance toward the open eye with only a few binocular cells remaining. The changes were accompanied by an extremely high incidence (38%) of abnormal cells lacking orientation selectivity across different ocular dominance groups. In kitten cortex infused with 10 mM antagonist concurrently with monocular deprivation for a week, recording from a drug-affected region near the infusion centre, we again found the U-shaped ocular dominance distribution with the high incidence of non-selective cells. In antagonist-infused, otherwise normal striate cortex of adult cats, we found that the proportion of binocular cells decreased by one-half in two cellular populations: one recorded during the continuous infusion of 10 mM antagonist under general anaesthesia and paralysis, and the other about two days after stopping the infusion. We also established that in vivo concentrations of chronically infused 10 mM antagonist decreased, not near-exponentially, but linearly with increasing distance from the infusion site. Thus, the effects of a directly and continuously infused, concentrated antagonist of N-methyl-D-aspartate receptors on receptive-field properties of visuocortical cells are complex. The present findings strongly suggest that the antagonist effects in the developing cortex may be due primarily to blockade of normal synaptic transmission rather than specific disruption of an experience-dependent mechanism underlying ocular dominance plasticity.

Restoration of ocular dominance plasticity mediated by adenosine 3',5'-monophosphate in adult visual cortex.

Noradrenaline (NA)-stimulated beta-adrenoreceptors activate adenylate cyclase via excitatory G-proteins (Gs). Activated adenylate cyclase in turn promotes the production of cAMP. Critical roles of cAMP-dependent protein kinase A (PKA) in divergent cellular functions have been shown, including memory, learning and neural plasticity. Ocular dominance plasticity (ODP) is strongly expressed in early postnatal life and usually absent in the mature visual cortex. Here, we asked whether the activation of cAMP-dependent PKA could restore ODP to the aplastic visual cortex of adult cats. Concurrent with brief monocular deprivation, each of the following cAMP-related drugs was directly and continuously infused in the adult visual cortex: cholera toxin (a Gs-protein stimulant), forskolin (a Gs-protein-independent activator of adenylate cyclase) and dibutyryl cAMP (a cAMP analogue). We found that the ocular dominance distribution became W-shaped, the proportion of binocular cells being significantly lower than that in respective controls. We concluded that the activation of cAMP cascades rapidly restores ODP to the adult visual cortex, though moderately. The finding further extends the original hypothesis that the NA-beta-adrenoreceptors system is a neurochemical mechanism of cortical plasticity.

Wide difference between the cytotoxicity of the 11-alpha-and 11-beta-cyano analogues of tilivalline and their epimeric conversion.

Tilivalline (TV) possesses a pyrrolo[1,4]benzodiazepine nucleus and is cytotoxic toward mammalian cells. The 11-beta-cyano TV analogue (1) is about one hundred times more cytotoxic to mouse leukemia L1210 cells than TV itself. In contrast, the 11-alpha-cyano TV analogue (2), an epimer of 1, has only about one-hundredth the cytotoxicity of 1. It was found that epimerization proceeded between 1 and 2 under physiological conditions, and the cytotoxicity of 2 is thought to be caused mainly by 1 that was formed from 2 during incubation in medium.

Adrenergic regulation of visuocortical plasticity: a role of the locus coeruleus system.

Noradrenaline-beta-adrenoceptor-mediated neural plasticity in cat visual cortex exemplifies clearly established roles of the locus coeruleus system in brain function. The prime role of the noradrenaline-beta-adrenoceptor system in the regulation of ocular dominance plasticity is discussed in this chapter and includes a newly invented paradigm of ocular dominance changes under anesthesia and paralysis without benefit of visual attention. Based on our recent findings, we have sought to integrate positive contributions of muscarinic cholinergic receptors to the beta-adrenoceptor-mediated regulatory processes. The issue of "activity dependency" is important and we recognize the necessity of designing new studies in which relationships between activity dependency within the visual pathway and global neurochemical/cellular factors can be tested directly. Further, we critically reviewed the involvement of gamma-aminobutyric acidA type receptors and N-methyl-D-aspartate receptors in the regulation of ocular dominance plasticity.

Stroke incidence and case fatality in Shiga, Japan 1989-1993.

BACKGROUND: This paper describes incidence rates and case-fatality for sub-types of stroke using data collected in Takashima, Shiga, Japan, from 1989 to 1993 and compares these with similar registers in other parts of Japan. METHODS: Registered patients included all residents of the county who experienced a first-ever stroke. Stroke was defined as sudden onset of neurological symptoms which continued for a minimum of 24 hours or led to death. Almost all such patients are hospitalized in this country. Early case fatality was defined as patients who died within 28 days of stroke onset. Diagnosis of stroke type was based on clinical symptoms as well as computed tomography (CT) scans. RESULTS: Age-adjusted incidence rates for stroke per 100,000 population aged 35 years and older were 268.7 for men and 167.5 for women. The age-specific incidence rate of both cerebral infarction and cerebral haemorrhage increased with advancing age. The occurrence of cerebral infarction in men was twice as high as in women. The 28-day case fatality for all sub-types of stroke was 16.1% in men and 15.8% in women. Case fatality for cerebral infarction, cerebral haemorrhage, and subarachnoid haemorrhage was 10.7%, 22.4% and 28.6% respectively. CONCLUSIONS: Takashima County has a moderately high stroke incidence rate and case fatality compared with other similar studies in Japan. The incidence rate of cerebral infarction in men is twice that in women, while other sub-types of stroke showed smaller differences. In order to decrease the incidence of stroke in Japan, greater efforts at primary prevention will be necessary, in particular, it is important to prevent cerebral infarction in men.