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Background: While water intake is frequently recommended to prevent cerebral infarction (CI), only few studies have been published on this topic. Objectives: This study retrospectively estimated the daily non-alcohol drink (NAD) intake in CI patients before CI onset and compared it with NAD in healthy subjects. Methods: We performed a cross-sectional study on CI patients in 3 hospitals and healthy subjects in the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) study. Data from 1,287 subjects (274 CI patients and 1,013 healthy subjects) were used for the analyses. By dividing the CI patients into “increased”, “unchanged”, and “decreased” groups according to their current NAD intake, we compared the NAD intake between these 3 groups and healthy subjects by analyses of covariance and the post hoc test, adjusting for sex, age, surveyed month, body mass index, alcohol drinking history, and smoking history. Under the assumption that the NAD intake in the “unchanged” group was equal to the NAD intake before CI onset, the OR of less NAD intake for CI adjusting for the relevant variables in the “unchanged” group and the healthy subjects was calculated; the cut-off point was chosen using Youden’s index. Results: The mean age (mean ± SD) of the participants was 62.8 ± 9.3 years. One hundred and fifty-one patients (36 women) were included in the “increased” group; 105 (30 women), in the “unchanged” group; 18 (2 women), in the “decreased” group; and 1,013 (706 women), in the “healthy” group. The mean NAD intake was 1,702.5 ± 670.2 mL in the “increased” group, 1,494.2 ± 611.2 mL in the “unchanged” group, 1,268.0 ± 596.1 mL in the “decreased” group, and 1,720.6 ± 686.0 mL in the “healthy” group. After adjusting for the relevant variables, a significant difference in NAD intake between the groups was observed (F = 6.1, p < 0.001), and a post hoc test demonstrated significant differences (p < 0.05) in NAD intake between the “healthy” and “unchanged” groups, and between the “increased” and “unchanged” groups. The OR of less NAD intake (Conclusion: This study showed that daily NAD intake before CI onset in CI patients was less than that in healthy persons, indicating that sufficient intake of NAD may be protective for CI.

Individuals with an inactive acetaldehyde dehydrogenase 2 have an. elevated level of serum acetaldehyde after drinking alcohol, and this may cause an alcohol flushing response with symptoms such as facial flushing, tachycardia, headache, and nausea. Recent studies have suggested that the flushing response influences the association between alcohol consumption and various health-related outcomes. In the present study, we investigated the impact of the flushing response on the relationship between alcohol consumption and serum y -GTP levels in Japanese drinkers. We conducted a cross-sectional study of 521 Japanese drinkers (260 men and 261 'vomen) to examine the impact of the alcohol flushing response on the relationship between alcohol consumption and serum y -GTP levels. The subjects were divided into three groups according to the amount .of daily alcohol consumption. (low,20 g; moderate, 20-39 g;. and high,40 g). Multiple adjustments were performed with linear regression models to examine the association between daily alcohol consumption and serum y-GTP levels, adjusting for potential con- founders including the flushing response. We found that the proportion of flushers was significantly lower in the high alcohol consumption group than in the low consumption group. The results of a multivariable analysis showed that,serum y -GTP levels were significantly higher in the moderate and high consumption groups than in the low consumption group after. adjusting for all potential confounders other than the flushing response. In addition, the association between serum y -GTP levels and alcohol consumption was unchanged after adjusting for the presence of the flushing response. In conclusion, serum y -GTP levels increased with increasing alcohol-consumption regardless of the flushing response. Screening for heavy drinkers using serum y-GTP levels was very important to prevent alcohol-related diseases or health problems in health examination.

Background Although several epidemiological studies have suggested that high serum uric acid (SUA) levels are related to a decline in kidney function, only a few studies have investigated using cystatin C to calculate estimated glomerular filtration rate (eGFR). We aimed to clarify the relationship between SUA levels and kidney function assessed by cystatin C in a Japanese general community population without chronic kidney disease (CKD). Methods We conducted a community-based cross-sectional study that included 1086 healthy participants, aged 40–74 years, without CKD and not undergoing treatment of hyperuricemia, who had participated in the baseline survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. The preconditions for participation in this study were no past histories of cardiovascular disease or cancer, and not undergoing treatment for diabetes, hypertension, or dyslipidemia. We classified the participants into quartiles stratified by sex according to their SUA level and then examined the relationship with eGFR. The odds ratios for having a low eGFR, defined as the lowest quartile of eGFR (i.e., ≤78.4 mL/min/1. 73m2) was estimated according to SUA quartiles (men, Q1 ≤ 5.0, Q2 5.1–5.9, Q3 6.0–6.6, and Q4 ≥ 6.7; women, Q1 ≤ 3.8, Q2 3.9–4.3, Q3 4.4–4.9, and Q4 ≥ 5.0 mg/dL) after adjustment for age, body mass index, systolic blood pressure, HbA1c, high and low density lipoprotein cholesterol, and smoking and drinking habits. The adjusted mean of each quartile was also calculated. Results Multivariable-adjusted means of eGFR showed a graded decrease in higher SUA quartiles (men, Q1 90.5, Q2 88.0, Q3 83.5, and Q4 82.0; women, Q1 95.7, Q2 91.3, Q3 89.2, and Q4 86.7). In addition, the multivariable-adjusted odds ratios for having a lower eGFR (95% confidence interval) for each SUA quartile compared with Q1 was Q2 2.29 (0.98, 5.35), Q3 4.94 (2.04, 11.97), and Q4 8.01 (3.20, 20.04) for men, and was Q2 2.20 (1.12, 4.32), Q3 2.68 (1.39, 5.20), and Q4 4.96 (2.62, 9.41) for women. Conclusions There was a graded inverse relationship between mild elevations in SUA levels and eGFR assessed by cystatin C in an apparently healthy Japanese population without CKD. This association was similar in both men and women.

The purpose of this study was to investigate the relationship between the frequency of outpatient visits and hypertension control as determined from health insurance records. This 9-year cohort study in Japan was based on 518 participants with hypertension who underwent health checkups in 2004. Participants were aged 35-56 years and none had a history of cardiovascular or cerebrovascular disease. All were covered by the same employee health insurer. Mean annual outpatient visit days at a hospital/clinic during the 9-year period were classified within four quartiles (Q1, Q2, Q3, Q4). Uncontrolled hypertension was defined as a systolic blood pressure (BP) ⩾140 mm Hg and a diastolic BP ⩾90 mm Hg. Logistic regression analysis was used to estimate the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the prevalence of uncontrolled hypertension in groups Q1, Q2 and Q3 vs. Q4. The median (25th-75th percentile) annual outpatient visit days was 9.4 (4.0-15.5). Uncontrolled hypertension was observed in 62.4% of the participants in 2013. The multivariable-adjusted ORs and 95% CIs for uncontrolled hypertension in Q1, Q2 and Q3 vs. Q4 were 4.03 (2.28-7.12), 1.67 (0.99-2.81) and 1.44 (0.86-2.41), respectively. Uncontrolled hypertension increased significantly as the number of outpatient visits decreased (P for trend

Background: An immediate ambulance call offers the greatest opportunity for acute stroke therapy. Effectively using ambulance services requires strengthening the association between knowledge of early stroke symptoms and intention to call an ambulance at stroke onset, and encouraging the public to use ambulance services. Methods: The present study utilized data from the Acquisition of Stroke Knowledge (ASK) study, which administered multiple-choice, mail-in surveys regarding awareness of early stroke symptoms and response to a stroke attack before and after a 2-year stroke education campaign in two areas subject to intensive and moderate intervention, as well as in a control area, in Japan. In these three areas, 3833 individuals (1680, 1088 and 1065 participants in intensive intervention, moderate intervention, and control areas, respectively), aged 40 to 74 years, who responded appropriately to each survey were included in the present study. Results: After the intervention, the number of correctly identified symptoms significantly associated with intention to call an ambulance (P < 0.05) increased (eg, from 4 to 5 correctly identified symptoms), without increasing choice of decoy symptoms in the intensive intervention area. Meanwhile, in other areas, rate of identification of not only correct symptoms but also decoy symptoms associated with intention to call an ambulance increased. Furthermore, the association between improvement in the knowledge of stroke symptoms and intention to call an ambulance was observed only in the intensive intervention area (P = 0.009). Conclusions: Our results indicate that intensive interventions are useful for strengthening the association between correct knowledge of early stroke symptoms and intention to call an ambulance, without strengthening the association between incorrect knowledge and intention to call an ambulance.

The present study sought to clarify if being conscious of water intake (CWI) is associated with sufficient non-alcohol drink (NAD) intake. We used data of healthy participants without diabetes, aged 40−74 years, in the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) study. The association between being CWI and NAD intake was evaluated by multivariate linear regression analyses after adjusting for age, sex, surveyed months (seasons), alcohol drinking, health-awareness life habits, socioeconomic factors, serum osmolarity, estimated daily salt intake, and reasons for NAD intake. Among 988 (698 women and 290 men) participants eligible for the present analyses, 644 participants (65.2%) were CWI and 344 participants (34.8%) were not CWI (non-CWI). The most popular reason for being CWI was to avoid heat stroke in summer and to prevent ischemic cerebral stroke in winter. The CWI group took more NAD, especially decaffeinated beverages, than the non-CWI group (1846.7 ± 675.1 mL/day vs. 1478.0 ± 636.3 ml/day, p < 0.001). There was a significant association between being CWI and NAD intake in multivariate linear regression analyses ever after adjusting for the relevant variables (β = 318.1, p < 0.001). These findings demonstrated CWI, regardless of the reasons and the seasons, was associated with high NAD intake in Japanese healthy population.

Background: It is important that the general population be aware of the early symptoms, since it has been shown that early arrival to hospitals leads better prognosis of stroke patients. However, the general population is not well informed about the early symptoms of stroke. This study was conducted to clarify which stroke symptoms are less well known and which information sources are related to awareness of stroke symptoms. Methods: A multiple-choice, mail-in survey involving 5,540 randomly selected residents, aged 40-74 years, of 3 cities in Japan was conducted. Their knowledge about stroke symptoms and their information sources were surveyed; information sources were classified as mass media (television/newspaper/radio) and personal communication sources (posters/leaflets/internet/health professionals/family and/or friends). ‘Awareness' was defined as selecting all 5 of the correct stroke symptoms from among 10 listed symptoms with decoy choices. The estimated fraction of the possible impact due to each source on the whole population was also calculated by odds ratios (ORs) and the proportion of respondents who selected each source (Pe). The combined effects of mass media and personal communication sources on awareness were also assessed. Results: Of the 5,540 residents, only 23% selected all 5 correct symptoms. Visual disturbance was the least known of the 5 symptoms (35%). All sources were positively related to awareness, with ORs (Pe) of: television, 1.58 (72.5%); newspaper, 1.79 (48.0%); radio, 1.74 (13.3%); posters, 1.73 (7.6%); leaflets, 1.50 (24.7%); Internet, 1.66 (5.6%); health professionals, 1.33 (34.8%), and family/friends, 1.21 (44.6%). The estimated fraction of the possible impact due to each source was higher for mass media (television, 0.31 and newspaper, 0.28) than personal communication sources (Internet, 0.04 and leaflets, 0.12). Mass media only and mass media/personal communication sources were significantly associated (ORs: 1.66, 2.75, respectively). Conclusions: As a single method of public education, television could be the most effective strategy. Moreover, the combined approach involving mass media and personal communication sources might have a synergistic effect. Less well-known symptoms, such as visual disturbances, should be noted in public education campaigns.

The validity of regular use of antiplatelet agents was retrospectively assessed in 106 patients with intracerebral hemorrhage (ICH) (supratentorial hemorrhage 92, lobar 22 and deep 70; and infratentorial hemorrhage 14) who underwent T(2)*-weighted gradient-echo magnetic resonance (MR) imaging between January 2005 and December 2006 in Kishiwada City Hospital. The prevalence of cerebral microbleeds was 54.7% (58/106), and the presence was significantly associated with higher age (odds ratio 3.09, p = 0.007), presence of white matter hyperintensity on T(2)-weighted MR imaging (odds ratio 2.36, p = 0.032), and previous ICH and/or cerebral infarction (odds ratio 4.77, p = 0.020). Previous ICH and/or cerebral infarction was independently associated with the presence of cerebral microbleeds after adjustment for age, white matter hyperintensity, and hypertension (odds ratio 4.07, p = 0.043). Regular use of antiplatelet agents was not associated with the presence of cerebral microbleeds, whether the patients had cerebrovascular diseases or not. Our findings suggest that antiplatelet medication can be justified for patients with cerebral microbleeds.

SummaryPlatelet-derived microparticles (PDMPs), a procoagulant factor, are reportedly elevated in type 2 diabetes mellitus and acute coronary syndrome. The metabolic syndrome (MS) is strongly associated with cardio- and cerebrovascular disease-related atherothrombotic events. To clarify the level, distribution and correlates of PDMPs with special reference to MS, we conducted a cross-sectional study of 467 healthy Japanese volunteers without signs, symptoms, or a history of cardio- or cerebrovascular disease. They were 211 men and 256 women (median age 39 and 35 years, respectively). Using an ELISA kit and monoclonal antibodies against CD42b and CD42a (glycoprotein Ib and IX) we assayed the PDMP levels. Total cholesterol, low-density and high-density lipoprotein cholesterol, remnant cholesterol, triglycerides, C-reactive protein, and traditional cardiovascular risk factors were also recorded. There was a significant difference in the level of PDMPs between men and women. The median value and the interquartile range of PDMPs was 8.3 IU/ml and 6.2 – 10.5 IU/ml and 6.8 IU/ml and 5.2 – 8.6 IU/ml, respectively, in men and women. PDMPs were significantly associated with MS criteria in men (p

We investigated the skeletal muscles of nine strains of senescence accelerated mouse (SAM), DDD, AKR/J, C57BL/6J, A/J and BALB/c mice. We found that male SAMP8, SAMP7, C57BL/6J, A/J and BALB/c mice expressed tubular aggregates (TAs) in their skeletal muscle. Among these strains, the SAMP8 strain, which exhibits a short life span and various age-associated neurodegenerative disorders plus mitochondrial dysfunction, showed TAs more markedly than the others. Thus, we compared SAMP8 mice against SAMR1 mice, an accelerated senescence-resistant strain. Light- and electron micrographs showed that male SAMP8 mice exhibited an age-dependent aggravation of TA accumulation. There were no significant differences in the serum lactate/pyruvate levels between the SAMP8 and SAMR1 mice. However, the serum creatine kinase (CK) levels of the 3 and 6-month-old SAMP8 mice were higher than that of the corresponding SAMR1 mice. Considering the serum CK levels and the mitochondrial dysfunction of SAMP8 mice, we conclude that the TAs may be involved in the homeostasis of energy metabolism that is not appropriately regulated in the SAMP8 mouse mitochondrion.

The effects of aminoguanidine supplementation on senescence acceleration in vitro were examined in fibroblasts from the dorsal dermis of newborn SAMP II (accelerated senescence-prone mice), and were compared to the effects in cell lines from SAMRI (accelerated senescence-resistant) mice. Four millimow aminoguanidine supplementation signijicantly de­ layed the senescencelcrisis in eel/lines from SAMP 11 mice, but did not affect the senescencelcrisis in cell lines from SAMRI mice. Flow cytometric analysis of the DNA content of confluent cells revealed that aminoguanidine supplementa­ tion signijicandy decelerated the increase in the number of tetraploid cells until senescencelcrisis. Although mean concen­ trations of lipid peroxides in the primary cultures did not differ signijicantly, considerably higher lipid peroxidatWn was ob­ served in some SAMPll cultures, and aminoguanidine supplementation reduced them to the levels in SAMRI cultures. These results strongly suggest that oxidative stress derivedfrom polyamine catabolism may contribute to the senescence ac­ celeration in vitro in eel/lines from SAMPII mice.

The preventive effect of aggressive blood pressure lowering on hematoma enlargement was investigated in patients with ultra-acute spontaneous intracerebral hemorrhage (ICH). Retrospective review of 248 patients (145 males, 103 females) with spontaneous ICH treated in our hospital between 2005 and 2008 identified patients with ultra-acute ICH who were directly taken to our institute by ambulance within 3 hours after onset. Patients who could not be assessed twice by computed tomography (CT) within 24 hours after arrival were excluded. Systolic blood pressure (SBP) was aggressively controlled in all patients using intravenous nicardipine to below 140 mmHg as soon as possible after diagnosis of ICH with CT. Hematoma enlargement was defined as increase in volume of more than 33% or more than 12.5 ml in the first 24 hours. Hematoma enlargement was observed in 11 of the 73 patients (15.0%). The time course of SBP change was not significantly different in patients with and without hematoma enlargement. The incidence of hematoma enlargement in patients with ultra-acute ICH in this study was 15.0%, which was lower than that in other series in which blood pressure was not reduced aggressively. This finding suggests that aggressive SBP lowering to below 140 mmHg has a preventive effect on hematoma enlargement in patients with ultra-acute ICH.

A 67-year-old woman presented with symptomatic infarction in the territory of the anterior inferior cerebellar artery manifesting as vertigo, vomiting, and right facial weakness. Basiparallel anatomic scanning (BPAS) magnetic resonance (MR) imaging combined with MR angiography demonstrated the occluded anterior inferior cerebellar artery. Common anatomic variations and limited detection of the smaller branches on MR angiography sometimes hinder evaluation of the occluded artery. BPAS-MR imaging may have a supplementary role to MR angiography in the diagnosis of cerebellar artery occlusions.

The aim of this study was to clarify the correlation and association of plasma IL-6 and PDMPs, both of which are associated with metabolic syndrome, in healthy individuals.We conducted a cross-sectional study of 464 healthy Japanese volunteers (210 men and 254 women, median age 39 and 35years, respectively) who had no signs, symptoms or history of cardiovascular- or cerebrovascular disease and took no medications. We assayed their IL-6 levels with a conventional ELISA kit and their PDMP levels by ELISA and monoclonal antibodies against CD42b and CD42a (glycoprotein Ib and IX).By multivariate analysis, the plasma level of PDMP was correlated with diastolic blood pressure (p=0.015), platelet count (p0.001), high sensitivity C-reactive protein, and the plasma level of IL-6 (p0.001) in men (R(2)=0.454, p0.001) and was correlated with platelet count (p0.001) and the plasma level of IL-6 (p0.001) in women (R(2)=0.159, p0.001). Quartile range of plasma level of IL-6 was associated with plasma level of PDMP after adjustment for diastolic blood pressure, platelet count, and high sensitivity C-reactive protein in men (p0.001) and associated with plasma level of PDMP after adjustment for platelet count in women (p0.001).These results suggest the plasma IL-6 is correlated and associated with the plasma PDMPs, markers of activated platelets in healthy individuals.

Purpose Those who have brain metastases smaller than 30 mm in diameter and less than 5 in number can be treated less invasively with radiosurgery. This retrospective study evaluated the optimal brain magnetic resonance image (MRI) follow-up interval for non-small cell lung cancer (NSCLC) patients to detect radiosurgically manageable metachronous brain metastases (MBM). Patients and methods The records of 551 patients with primary NSCLC, treated in our institute between 2002 and 2007, were reviewed. The initial brain MRI was performed within one month after diagnosis of NSCLC, and the follow-up brain MRI interval was at the discretion of physicians. The interval between the last MRI in which brain metastases were not found and the first MRI in which brain metastases were found was defined as the critical MRIs interval (CMI). The relationship between CMI and the maximum size or number of MBM was evaluated. Results Among reviewed patients, the initial MRI of 38 patients showed brain metastases and 29 patients were diagnosed as MBM. In these MBM patients, the median interval from diagnosis of NSCLC to diagnosis of brain metastases was 8.9 months. The median CMI was 4.7 (range: 1.6–18.9) months. All brain metastases smaller than 30 mm in maximum diameter were found when CMI was shorter than 6.0 months, although 5 or more brain metastases in number were detected even by shorter CMI than 3 months. Conclusion Early detection of MBM by biannual MRI follow-up may provide NSCLC patients with more opportunities to have less invasive treatment.

Objective Cerebral microbleeds (CMB) on gradient-echo T2*-weighted magnetic resonance image (MRI) are frequently seen in patients with cerebral diseases. In this observational study we assessed whether CMB are a predictive factor for first-ever cerebrovascular events. Patients and methods This study consisted of 698 subjects without a history of symptomatic cerebrovascular events, who received gradient-echo T2*-weighted MRI for 3 months between November 2003 and January 2004 in Kishiwada City Hospital, Osaka, Japan. These subjects were then observed as outpatients for over 3.5 years. Results The prevalence of CMB at baseline was 17.0% (119/698) in this population, and the follow-up rate was 51%. A total of 36 first-ever symptomatic cerebrovascular events were observed during the 3 and a half-year follow-up period. First-ever symptomatic cerebrovascular events occurred significantly more frequently in subjects with CMB (15 cases) than those without CMB (21 cases) ( p =0.001). Even after adjusting for age, sex and hypertension, it was revealed that the presence of CMB was an independent predictor for the first-ever symptomatic cerebrovascular event by using the Cox proportional hazards model (hazard ratio, 2.87; 95% CI, 1.27–6.48; p =0.01). Conclusion The presence of CMB is an independent predictor of first-ever symptomatic cerebrovascular diseases.

Background: In patients suffering from intracerebral hemorrhage (ICH) with ventricular hemorrhage (IVH), the IVH severity is thought to be associated with prognosis. Therefore, treating IVH may be a beneficial therapeutic target. In this study, by examining the associations among IVH severity, hydrocephalus, initial level of consciousness and prognosis, we attempted to identify which grade of IVH severity should be considered for surgical treatment. Methods: One hundred twenty-nine patients with spontaneous supratentorial ICH treated in our hospital between 2005 and 2006 were screened in this study. Of these patients, 100 with an ICH volume less than 60 ml were categorized into either the ICH patients without IVH (no-IVH) group (n = 65) or the ICH patients with IVH (IVH) group (n = 35). The Karnofsky Performance Status (KPS) scale assessed at the time of discharge was employed as an outcome index, and a KPS score of ≤40 was defined as the bedridden state. Age, gender, hemorrhage location, volume of ICH, IVH grade (according to the Graeb score), acute hydrocephalus, surgical ICH removal, and ventricular drainage were selected for univariate analyses with logistic regression. Results: Elderly patients, IVH volume, acute hydrocephalus, and poor initial level of consciousness were significantly associated with an unfavorable prognosis in the IVH group. Poor level of consciousness was significantly dependent on acute hydrocephalus, and significantly more occurrences of acute hydrocephalus were found in patients with a high IVH volume (Graeb score ≥6) than in patients with low to moderate IVH volume (Graeb score ≤6). Conclusions: IVH severity influenced the occurrence of acute hydrocephalus and initial level of consciousness, which was significantly associated with prognosis. Our results suggest that priority treatment of the IVH should be given to those ICH patients with IVH admitted with a Graeb score of 6 or more.

The objective of this study was to clarify the relationship between circulating oxidized LDL (oxLDL) and metabolic syndrome (MS) and the coronary heart disease (CHD) risk score.We conducted a cross-sectional study of healthy volunteers who had no signs, symptoms or history of cardiovascular or cerebrovascular disease and took no medications. We studied 382 Japanese volunteers, 190 men and 192 women (median age 41 and 38 years, respectively). We used an ELISA kit and a monoclonal oxLDL antibody, FOH1a/DLH3, to measure circulating oxLDL.The odds ratio (OR) for elevated oxLDL in individuals with MS compared to those without MS, adjusted for age and sex, was 1.94 (range 1.00-3.78). In individuals with a predicted Framingham 10-year risk for CHD5% (corresponding with the highest quartile), compared to those with a predicted 10-year risk5%, the OR, adjusted for age, sex, smoking, and LDL cholesterol, was 2.51 (1.17-5.36). The age-, sex-, smoking- and LDL cholesterol-adjusted OR for a 10-year CHD risk score5% was 1.03 (1.01-1.04) for LDL cholesterol and 11.7 (4.69-29.0) for smoking.Elevated oxLDL is associated with the presence of MS and the CHD risk score in healthy people.

A 62-year-old woman presented with general malaise persisting for 2 months and narrowing of her visual field. T1-weighted magnetic resonance (MR) imaging showed swelling of the pituitary gland and stalk, and a homogeneous isointense intra- and suprasellar mass enhanced by gadolinium. During outpatient follow up, her condition deteriorated rapidly and she developed diabetes insipidus and panhypopituitarism. T1-weighted MR imaging demonstrated shrinkage of the lesion and disappearance of the central hypointense area indicating the cyst cavity, especially in the pituitary stalk. She underwent surgical exploration via the transsphenoidal approach under a provisional diagnosis of lymphocytic hypophysitis. Histological examination revealed ciliated columnar cells and squamous metaplasia on the inner surface of the cyst wall, with many foamy cells, infiltration by many lymphoid cells and some eosinophils, and fibrosis in the adenohypophysitis and inflammatory hypophysitis in the anterior and posterior pituitary gland. The present neuroimaging findings of cyst shrinkage associated with rapid clinical deterioration strongly support the suggestion that rupture of Rathke's cleft cyst causes inflammatory hypophysitis.

We conducted a population-based study on glioblastomas in the Canton of Zurich, Switzerland (population, 1.16 million) to determine the frequency of major genetic alterations and their effect on patient survival. Between 1980 and 1994, 715 glioblastomas were diagnosed. The incidence rate per 100,000 population/year, adjusted to the World Standard Population, was 3.32 in males and 2.24 in females. Observed survival rates were 42.4% at 6 months, 17.7% at 1 year, and 3.3% at 2 years. For all of the age groups, younger patients survived significantly longer, ranging from a median of 8.8 months (50 years) to 1.6 months (80 years). Loss of heterozygosity (LOH) 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16(INK4a) deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations and was predictive of shorter survival. Primary (de novo) glioblastomas prevailed (95%), whereas secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hotspot codons 248 and 273, whereas in primary glioblastomas, mutations were more equally distributed. G:C--A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas (56% versus 30%; P = 0.0208). This suggests that the acquisition of TP53 mutations in these glioblastoma subtypes occurs through different mechanisms.

Accelerated changes in the DNA ploidy associated with in vitro aging were examined in fibroblast-like cells isolated from the dorsal dermis of newborn SAMP11 (accelerated senescence-prone, short-lived) mice, and were compared to changes observed in cell lines from SAMR1 (accelerated senescence-resistant, long-lived) mice. Flow cytometric analysis of the DNA content in confluent cells and chromosome analysis in mitoses revealed that the diploid cells were being replaced with tetraploid cells until a growth crisis; thereafter, hypotetraploid cells became predominant, accompanied by immortalization. The number of mitoses decreased as the crisis ensued, then increased. Although these changes were observed in the cell lines from both strains of mice, the changes occurred more rapidly and at earlier population doublings in the cell lines from the SAMP11 mice. These results suggest that the cell lines from SAMP11 mice might have higher susceptibility to factors that cause polyploidization, including oxidative stress.

Fibroblast-like cells were isolated from the senescence accelerated mouse (SAM) and cultured, after which evidence of accelerated senescence was sought. Fibroblast-like cell lines were established from the dorsal dermis of neonate mice of both the accelerated senescence-prone strain, SAMP11 and the accelerated senescence-resistant strain, SAMR1. All cell lines from both strains showed a crisis in growth and were immortalized. At crisis, all cultures were composed of morphologically characteristic senescent cells. However, in cell lines from SAMP11, this change was more rapid and at earlier population doublings (PDs) than seen in cell lines from SAMR1. Crises (SAMP11; SAMR1) were also operationally taken to be the point of the least change in PDs (11.2 +/- 1.1; 15.4 +/- 0.5 PDs), the least saturation density (11.3 +/- 0.8; 19.1 +/- 2.6 PDs), and the longest population doubling time (10.1 +/- 0.8; 14.2 +/- 0.6 PDs). Crisis occurred significantly earlier (P0.05) and the aging process was accelerated in cell lines from SAMP11, compared with lines from SAMR1. This evidence tends to support various observations made in the accelerated senescence-prone strains of SAMP, in vivo.