Role of the renin-angiotensin system in gynecologic cancers.

Recent studies have shown an activation of the local renin-angiotensin system (RAS) in various tumor tissues, including the abundant generation of angiotensin II (Ang II) by angiotensin-converting enzyme (ACE) and the upregulation of angiotensin II type 1 receptor (AT1R) expression. Thus, considerable attention has been paid not only to the role of the RAS in cancer progression, but also to the blockade of RAS as a new approach to the treatment of human cancer. There is increasing evidence that the Ang II-AT1R pathway is involved in tumor growth, angiogenesis and metastasis in various experimental animal models, suggesting the therapeutic potential of an ACE inhibitor and AT1R blocker. In addition, specific Ang II-degrading enzymes are also expressed in tumors and play a regulatory role in tumor cell proliferation and invasion. This review focuses on the role of the RAS in the progression of gynecologic cancers, such as cervical cancer, endometrial cancer, ovarian cancer, and gestational choriocarcinoma. We present here the clinical potential of blocking the RAS as a novel and promising strategy for the treatment of gynecologic cancers.

Insulin resistance is associated with the pathology of Alzheimer disease: the Hisayama study.

OBJECTIVE: We examined the association between diabetes-related factors and pathology of Alzheimer disease (AD) to evaluate how diabetes affects the pathogenic process of AD. METHODS: This study included specimens from a series of 135 autopsies of residents of the town of Hisayama in Fukuoka prefecture (74 men and 61 women) performed between 1998 and 2003, who underwent a 75-g oral glucose tolerance test in clinical examinations in 1988. We measured diabetes-related factors including fasting glucose, 2-hour post-load plasma glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in 1988. Neuritic plaques (NPs) were assessed according to the Consortium to Establish a Registry for Alzheimer's Disease guidelines and neurofibrillary tangles (NFTs) were assessed according to Braak stage. The associations between each factor and AD pathology were examined by analysis of covariance and logistic regression analyses. RESULTS: Higher levels of 2-hour post-load plasma glucose, fasting insulin, and HOMA-IR were associated with increased risk for NPs after adjustment for age, sex, systolic blood pressure, total cholesterol, body mass index, habitual smoking, regular exercise, and cerebrovascular disease. However, there were no relationships between diabetes-related factors and NFTs. Regarding the effects of APOE genotype on the risk of AD pathology, the coexistence of hyperglycemia and APOE epsilon4 increased the risk for NP formation. A similar enhancement was observed for hyperinsulinemia and high HOMA-IR. CONCLUSION: The results of this study suggest that hyperinsulinemia and hyperglycemia caused by insulin resistance accelerate NP formation in combination with the effects of APOE epsilon4.

Trends in prevalence of Alzheimer's disease and vascular dementia in a Japanese community: the Hisayama Study.

OBJECTIVE: To examine secular trends in the prevalence of Alzheimer's disease (AD) and vascular dementia (VD) in a general Japanese population. METHOD: Four cross-sectional examinations were conducted among residents of a Japanese community aged >or=65 in 1985, 1992, 1998 and 2005. RESULTS: The age- and sex-adjusted prevalence of all-cause dementia significantly increased with time (6.0% in 1985, 4.4% in 1992, 5.3% in 1998 and 8.3% in 2005; P for trend = 0.002). A similar trend was observed for AD (1.1%, 1.3%, 2.3% and 3.8% respectively; P for trend < 0.001), while the age- and sex-adjusted prevalence of VD and other/unclassified dementia showed J-shaped patterns (for VD: 2.3%, 1.5%, 1.5% and 2.5%, respectively, P for trend = 0.82; for other/unclassified dementia: 2.6%, 1.7%, 1.5% and 2.0%, P for trend = 0.26). The prevalence of AD was likely to increase with time from 1985 to 2005 among subjects aged 75 or older. The ratio of the prevalence of VD to that of AD decreased with time (2.1 in 1985, 1.2 in 1992, 0.7 in 1998 and 0.7 in 2005). CONCLUSION: Our findings suggest that the prevalence of all-cause dementia and AD significantly increased over the past two decades in the general Japanese population.

Incidence and survival of dementia in a general population of Japanese elderly: the Hisayama study.

OBJECTIVE: To estimate the incidence and survival rates of total and cause specific dementia in a general Japanese population. METHODS: A total of 828 subjects without dementia, aged 65 years or over, were followed-up prospectively for 17 years. Dementia was subdivided into cause specific subtypes: namely, Alzheimer's disease (AD), vascular dementia (VD), dementia with Lewy bodies (DLB), combined dementia and other types of dementia. During the follow-up, 275 subjects developed dementia; of these, 251 (91.2%) were evaluated morphologically, with 164 subjected to brain autopsy examination and the remaining 87 to neuroimaging. RESULTS: The incidences of total dementia, AD, VD, DLB, combined dementia and other types of dementia were 32.3 (n = 275), 14.6 (124), 9.5 (81), 1.4 (12), 3.8 (33), and 3.1 (16) per 1000 person years, respectively. The incidences of AD, combined dementia and other types of dementia rose with increasing age, particularly after the age of 85 years, but this tendency was not observed for VD or DLB. The survival curve of dementia cases aged 65-89 years was significantly lower than that of age and sex matched controls (10 year survival rate, 13.6% vs 29.3%; hazard ratio 1.67; 95% confidence interval 1.31 to 2.13). The 10 year survival rates were not significantly different among dementia subtypes. CONCLUSIONS: Our findings suggest that the Japanese elderly population has a high risk for the development of dementia, specifically AD and VD, and once dementia is established, the risk of death is considerable.

Effect of long-term and low-dose administration of erythromycin on proliferation of T lymphocytes stimulated with mitogens.

The aim of the study was to assess the effect of long-term low-dose erythromycin (EM) treatment for chronic airway inflammation on proliferation of T cell subsets when stimulated with concanavalin A (Con A) and phytohemagglutinin (PHA). CD8+ cells are much more responsive to Con A compared to PHA. Ten patients with bronchiectasis were administered EM at 400 mg daily for 6 months. The extent of proliferation was assayed by [(3)H] thymidine incorporation and expressed as a stimulation index (SI). The lymphocyte subsets were analyzed including CD3+, CD4+ and CD8+ cells. The SI stimulated with Con A in the last month of therapy was significantly lower compared with that before the start of therapy (p=0.015) and 3 months after the end of therapy (p=0.002). However, EM therapy did not make a significant difference to the SIs when stimulated with PHA. CD3+, CD4+ and CD8+ cells in absolute numbers and CD4+/CD8+ ratios were not different among those harvested at the three time points. Long-term administration of EM may decrease the transformation response of CD8+ cells in patients.

Polymorphism in the sorbin and SH3-domain-containing-1 (SORBS1) gene and the risk of brain infarction in the Japanese population: the Fukuoka Stroke Registry and the Hisayama study.

BACKGROUND AND PURPOSE: Sorbin and SH3-domain-containing-1 (SORBS1) is an important adaptor protein in insulin-signalling pathway, and its genetic polymorphism may regulate the activity of insulin resistance. We investigated the association between the SORBS1 T228A polymorphism and ischaemic stroke. METHODS: Genotyping was achieved by a rapid-cycle PCR and melting curve analysis using fluorescent probes in 1049 incident cases of ischaemic stroke and 1049 age- and sex-matched control subjects recruited from the Hisayama study. RESULTS: The allele distributions of the SORBS1 T228A polymorphism were similar amongst cases and controls. The multivariate-adjusted odds ratio (OR) of the AA genotype for ischaemic stroke was 2.897 (95% CI, 0.907-8.018) compared with the TT genotype. In terms of stroke subtype, there was a trend toward a difference in the AA genotypes for lacunar infarction, compared with the TT genotype (OR = 8.740, P = 0.0510), and combined TT and TA genotypes (OR = 8.768, P = 0.0505). The other polymorphisms genotyped were not associated with any subtypes of ischaemic stroke. T228A polymorphism of SORBS1 was not associated with the prevalence of diabetes. CONCLUSIONS: The AA genotype of SORBS1 T228A polymorphism may play a role in lacunar infarction in the Japanese population.

NAD(P)H oxidase p22phox C242T polymorphism and ischemic stroke in Japan: the Fukuoka Stroke Registry and the Hisayama study.

The C242T polymorphism of p22phox, a component of NAD(P)H oxidase, may have an impact on cardiovascular diseases; however, the association between this polymorphism and brain infarction is not fully understood. Here, we investigate the relationship between the C242T polymorphism and brain infarction in Japan. We recruited 1055 patients with brain infarction and 1055 control subjects. A chi-squared test revealed that the T-allele frequency was lower in patients with cardioembolic infarction (5.6%) than in control subjects (11.0%, P < 0.001); however, allele frequencies in patients with lacunar and atherothrombotic infarction (11.2%) were not significantly different from those in control subjects (11.0%). A multivariate-adjusted conditional logistic regression analysis also revealed no association between CT + TT genotype, and lacunar and atherothrombotic infarction (odds ratio = 0.97, 95% confidence interval: 0.72-1.32). To investigate the functional effects of the C242T polymorphism, we examined superoxide production in COS-7 cells cotransfected with Nox4 and p22phox of each genotype. The superoxide-producing activity in those cells expressing p22phox with the T allele was not significantly different from that in cells expressing p22phox with the C allele. The present results suggest that the p22phox C242T polymorphism may have a protective effect against cardioembolic infarction, but is not related to lacunar and atherothrombotic infarction in Japan.

Tentorial papillary meningioma in a child: case report and review of the literature.

We report a usual case of papillary meningioma arising from tentorium cerebelli occurring in a 13-year-old boy. This patient presented a 3-month history of a mildly poor coordination of the left side of his body. Computed tomography showed a homogenous enhanced mass lesion in the left posterior fossa. At surgery, gross total resection of the tumor was accomplished. Upon microscopic examination, some tumor cells were arranged in the papillary pattern and a resulting diagnosis of papillary meningioma was made. Electron microscopic studies showed typical meningioma features such as interdigitations and desmosomes, which were, however, detectable in only few tumor cells. Cytological and ultrastructural features of pediatric papillary meningioma and of high-grade meningioma in general are sparse. Since papillary meningioma rarely presents in children, we report this case and review the literature.

Primary germinoma arising from the midbrain.

A 29-year-old man presented with diplopia, dysarthria, anisocoria, oculomotor nerve paralysis, abducens nerve paralysis, right facial palsy, and spastic hemiparetic gait. Magnetic resonance imaging (MRI) showed a homogenously enhanced mass in the midbrain. MRI-guided stereotactic biopsy was performed, and the histologic diagnosis was pure germinoma. The tumor disappeared after chemotherapy and radiotherapy. Germinoma should be included in the differential diagnosis of midbrain lesions in young adults. MRI-guided stereotactic biopsy provided a helpful diagnostic clue in a patient with a midbrain lesion.

Decreasing incidence of lacunar vs other types of cerebral infarction in a Japanese population.

BACKGROUND: There is scant information on secular trends in the incidence and survival of ischemic stroke subtypes. METHODS: The authors established three cohorts of Hisayama residents age > or =40 years in 1961 (1,618 subjects), 1974 (2,038 subjects), and 1988 (2,637 subjects). They followed up with each cohort for 12 years, comparing the incidence and survival rate of ischemic stroke subtypes. Morphologic examinations by autopsy or brain imaging was performed on most of the ischemic stroke cases in all cohorts. RESULTS: The age-standardized incidence of lacunar infarction significantly declined by 59% for men and by 28% for women from the first to the second cohort. It continued to decline by 41% for men, but the decline decelerated for women between the second and third cohort. The age-standardized incidence of atherothrombotic infarction tended to decline from the first to the second cohort, whereas it was sustained between the second and third cohort for both sexes. The age-standardized incidence of cardioembolic infarction was unchanged throughout the cohorts. In these cohorts, mean blood pressure levels among hypertensive subjects and the prevalence of current smoker decreased with time, though the prevalence of hypertension remained stable. The 5-year survival rate after lacunar infarction significantly improved among the cohorts, but those of atherothrombotic and cardioembolic infarction did not. CONCLUSIONS: These data suggest that, in the Japanese population, the incidence of lacunar infarction steadily declined for the last 40 years. The improvement of hypertension control and decreasing prevalence of smoking might be responsible for this trend.

Atypical teratoid/rhabdoid tumor arising from the spinal cord--case report and review of the literature.

Spinal atypical teratoid/rhabdoid tumor (AT/RT) is extremely rare. We report this rare case and review the literature of spinal AT/RT. A 10-month-old girl presented with rapidly progressive paraplegia. Magnetic resonance images revealed an intramedullary tumor occupying the entire spinal canal below Th10. An urgent operation, consisting of decompression by laminectomy and biopsy, was performed. Histologically, the tumor specimen had many rhabdoid cells with prominent nuclei and eosinophilic cytoplasmic inclusion. It showed mitosis and necrosis. The tumor cells were immunoreactive for vimentin, desmin, smooth muscle actin, neuron-specific enolase, neurofilament, epithelial membrane antigen, and CAM5.2. Despite chemotherapy and radiotherapy, she died 3 months after admission. The present case is only the third detailed report of spinal AT/RT. Spinal AT/RT carries a poor prognosis, and therefore should be distinguished from other embryonal tumor.

Ten year recurrence after first ever stroke in a Japanese community: the Hisayama study.

BACKGROUND: Very few population based cohort studies have focused on the long term recurrence of stroke. OBJECTIVE: To examine 10 year cumulative recurrence rates for stroke in a Japanese cohort according to pathological type and clinical subtype of brain infarction. METHODS: During a 32 year follow up of 1621 subjects >/=40 years of age, 410 developed first ever stroke. These were followed up prospectively for 10 years after stroke onset. RESULTS: During follow up, 108 (26%) experienced recurrent stroke. The cumulative recurrence rates were 35.3% at five years and 51.3% at 10 years. The 10 year recurrence rates of subarachnoid haemorrhage (SAH), brain haemorrhage, and brain infarction were 70.0%, 55.6%, and 49.7%, respectively; the difference between SAH and brain infarction was significant (p = 0.004). Most recurrent episodes after SAH or brain haemorrhage happened within a year after the index stroke, whereas recurrence of brain infarction increased consistently throughout the observation period. Cardioembolic stroke had a higher recurrence rate (75.2%) than lacunar infarction (46.8%) (p = 0.049). The 10 year risk of stroke recurrence increased with age after lacunar or atherothrombotic brain infarction, but not after the other types or subtypes. After atherothrombotic brain infarction, cardioembolic stroke, or SAH, the type and subtype of most recurrent strokes were the same as for the index stroke, but recurrence after lacunar infarction or brain haemorrhage showed divergent patterns. CONCLUSIONS: Japanese people have higher recurrence rates of stroke than other populations. Recurrence rate after a first brain infarct increases consistently through the next 10 years.

Incidence and prognosis of gastric cancer in a population-based cohort survey: the Hisayama study.

BACKGROUND: No population-based cohort studies have been undertaken to evaluate the incidence and prognosis of gastric cancer. The purpose of this investigation was to clarify the incidence and fatal prognosis of gastric cancer and to determine the factors that contribute to the prognosis in a general Japanese population in Hisayama using a prospective study design. METHODS: From 1988 to 1998 a total of 2605 subjects aged 40 years or older with no history of gastrectomy or gastric cancer were followed-up prospectively after a health examination. The diagnosis of gastric cancer was based on clinical records or autopsy findings. RESULTS: During the follow-up period, 76 subjects developed gastric cancer. The age-adjusted incidence of gastric cancer for men (4.9 per 1000 person-years) was 4-fold higher than that for women (1.2, P < 0.05). In men, the incidence of gastric cancer increased with advancing age, but this trend was not observed in women. The age- and sex-adjusted 5-year survival rate was significantly higher in cancers of the middle third of the stomach than in those of the upper third of the stomach. The survival rate was higher in cancers of well-differentiated adenocarcinoma than in those of the other histological types. There were no cases of cancer-related death among the early gastric cancers during the follow-up period. CONCLUSIONS: Our data suggest that men are at higher risk of gastric cancer than women in the general Japanese population. Clinical stage, histological type, and site of cancer in the stomach contribute to a fatal prognosis.

Influence of long-term cigarette smoking on immunoglobulin E-mediated allergy, pulmonary function, and high-resolution computed tomography lung densitometry in elderly patients with asthma.

BACKGROUND: Smoking is the most important cause of chronic obstructive pulmonary disease (COPD). However, the influence of cigarette smoking on the pathogenesis of asthma in the elderly remains controversial. This study attempted to clarify the influence of cigarette smoking on elderly asthmatics. METHODS: Forty-eight asthmatics over 70 years old (25 ex-smokers and 23 never-smokers) and 20 patients with COPD over 70 years old (all ex-smokers) were studied to determine the influence of cigarette smoking on IgE-mediated allergy (total IgE, IgE antibodies against inhalant allergens, bronchial hyper-responsiveness (BHR), generation of leukotriene (LT) B4 and C4), pulmonary function, and the relative area of lung showing attenuation values less than -950 Hounsfield units (RA950) on high-resolution computed tomography scans. RESULTS: The incidence of positive IgE antibodies against inhalant allergens, BHR, and the generation of leukotriene B4 (LTB4) by leucocytes were significantly increased in patients with a history of smoking compared with those without. Residual volume (%RV) was significantly increased, and diffusing capacity for carbon monoxide was significantly decreased in ex-smokers with asthma and COPD compared with never-smokers with asthma. Inspiratory RA950 and ratio of expiratory RA950 to inspiratory RA950 were significantly larger in asthmatics with a smoking history than in those without, and in COPD patients than in asthmatics. CONCLUSION: Cigarette smoking enhances the production of IgE antibodies, BHR, and generation of LTB4 by leucocytes in elderly asthmatics. Increased hyper-inflation or emphysematous changes of the lungs expressed by increased RA950, closely related to %RV, was more frequently observed in ex-smokers compared with never-smokers.

Importance of re-examination for medulloblastoma and atypical teratoid/rhabdoid tumor.

Medulloblastoma may can be difficult to distinguish from atypical teratoid/rhabdoid tumor (AT/RT), since they resemble each other histologically. We re-examined whether AT/RT was included among cases who had been diagnosed as medulloblastoma. All of fifteen medulloblastomas (10 males and 5 females) diagnosed at the Kitasato University Hospital were collected and stained immunohistochemically. Two cases originally diagnosed as medulloblastoma were reclassified as AT/RT based on histological re-examination including immunohistochemical studies. While these two cases of AT/RT were found during infancy, only one medulloblastoma was found in infancy.Histologically, small rhabdoid cells and large, pale, bland cells were common but typical rhabdoid cells were not seen in the two AT/RTs. Gland-like structures were also seen. The tumor cells in AT/RT, but not those in medulloblastoma, were immunoreactive for vimentin, epithelial membrane antigen and smooth muscle actin. In conclusion, if a diagnosis of medulloblastoma is made histologically, it should be confirmed immunohistologically, since it is difficult to distinguish AT/RT from medulloblastoma. When appropriate treatment was specifically targeted at AT/RT it may improve the outcome.

Decreased computed tomographic lung density during exacerbation of asthma.

Recently, it was shown that both mean lung density (MLD) and the relative lung area with an attenuation of <-950 HU (RA950) are related to severity of asthma in nonsmoking asthmatics. The aim of the present study was to examine whether reduced computed tomography (CT) lung density during exacerbation could change after treatment. A cross-sectional study was performed to compare CT lung density in 30 stable asthmatics, 30 unstable asthmatics and 25 control subjects. In order to investigate longitudinally the effect of treatment on decreased CT lung density, 17 asthmatics with an exacerbation were followed at the initiation of treatment and 2 months after relief. The MLD was significantly lower and the RA950 significantly higher in unstable asthmatics than in controls and stable asthmatics. Both MLD and RA950 changed significantly with administration of systemic glucocorticoid therapy. The changes in forced expiratory volume in one second correlated significantly with those in both MLD and RA950. The changes in residual volume also correlated significantly with those in both MLD and RA950. It was concluded that decreased computed tomographic lung density during an asthma exacerbation is at least partially reversible, and changes in mean lung density and the relative lung area with a radiation attenuation of <-950 HU are related to the change in forced expiratory volume in one second and residual volume.

A proton-pump inhibitor, rabeprazole, improves ventilatory function in patients with asthma associated with gastroesophageal reflux.

BACKGROUND: Treatment of gastroesophageal reflux (GER) with proton-pump inhibitors (PPI) improves symptoms of asthma in some patients. However, the effects of a PPI on ventilatory function are still controversial. In this study, we measured ventilatory function in asthma patients treated with a PPI in order to identify those in whom a therapeutic effect on asthma can be expected from the acid suppression. METHODS: From a cohort of 114 consecutive patients with bronchial asthma, 53 patients agreed to participate in the study and were treated with rabeprazole 20mg daily for 8 weeks during an asymptomatic, stable period with no exacerbations of their asthma. Of the 53 patients, 22 were diagnosed as GER on the basis of the QUEST questionnaire and endoscopic examination. The patients were monitored for improvement in ventilatory function. RESULTS: Four patients dropped out because of adverse drug reactions. All the patients with GER noted an improvement in reflux symptoms with PPI treatment. An improvement of more than 20% in peak expiratory flow (PEF) was observed in 8 of 21 GER patients but in none of the non-GER patients. Factors predictive of improvement in PEF with rabeprazole therapy were the QUEST score (odds ratio: 1.47, 95% CI: 1.06-2.04, P = 0.022) and steroid-dependency of asthma (odds ratio: 0.01, 95% CI: 0.001-0.31, P = 0.008). CONCLUSIONS: Treatment with rabeprazole is expected to ameliorate asthma in non-steroid-dependent patients who have symptomatic GER defined by the QUEST score.

Long-term outcome of intracranial germinoma with hCG elevation in cerebrospinal fluid but not in serum.

OBJECTIVE: Pure germinomas have a good prognosis compared to those with syncytiotrophoblastic giant cells (STGCs), which show elevated human chorionic gonadotropin or human chorionic gonadotropin-beta (hCG/hCG-beta) levels and relapse frequently. However, the long-term outcome of patients with germinoma and detectable hCG/hCG-beta in cerebrospinal fluid (CSF) but not in serum is unclear. MATERIALS AND METHODS: The outcome of patients with pure germinomas (no increase in hCG/hCG-beta in serum or CSF, 13 cases; group A), germinomas with STGC (increased hCG/hCG-beta in serum, 13 cases; group B) and germinomas with increased hCG/hCG-beta only in CSF (6 cases; group C) was analyzed. RESULTS: All three groups received similar radiotherapy. Groups A and C each showed a 10-year survival rate of 100%, while this was only 69.2% in group B. The 10-year relapse-free survival rates were 92.3%, 69.2% and 83.3% (groups A, B and C, respectively). Groups A and C each had one case of tumor relapse, but there was no recurrence simply by the application of radiotherapy. On the other hand, in group B, tumor relapse was seen in 4/13 (30.8%) cases. Three of them showed relapse within the region of the initial radiation exposure and died despite all available treatment. CONCLUSION: Patients with an increased hCG/hCG-beta level in CSF may be considered to be similar to pure germinomas and should be treated and followed-up carefully.

Vertebral fracture and cortical bone changes in corticosteroid-induced osteoporosis.

Despite an intriguing understanding of trabecular bone dynamics, little is known about corticosteroid-induced cortical bone loss and fractures. Recently, we verified a steroid-induced decrease in cortical bone volume and density using peripheral quantitative computed tomography (pQCT) in adult asthmatic patients given oral corticosteroids. Subsequently, the pQCT parameters and presence of vertebral fractures were investigated to further clarify the role of cortical bone quality in fractures in 86 postmenopausal (>5 years after menopause) asthmatic patients on high-dose oral steroid (>10 g cumulative oral prednisolone) (steroid group) and 194 age-matched controls (control group). Cortical and trabecular bone was subjected to measurement of various parameters using pQCT (Stratec XCT960). Relative Cortical Volume (RCV) was calculated by dividing the cortical area by the total bone area. Strength Strain Index (SSI) was determined in the radius based on the density distribution around the axis. Spinal fracture was assessed on lateral radiographs. Patients treated with high doses of oral steroid (>10 g cumulative oral prednisolone) were found to have an increased risk of fracture compared with control women receiving no steroid medication (odds ratio, 8.85; 95% CI, 4.21-18.60) after adjustment was made for years since menopause, body mass index and RCV. In both groups, the diagnostic and predictive ability of the pQCT parameters for vertebral fracture was assessed by the areas under their receiver operating characteristic (ROC) curves. All parameters were found to be significant predictors ( p<0.0001) in the control group. In the steroid group, however, the cortical bone mineral density (BMD) ( p = 0.001), RCV ( p<0.0001) and SSI ( p = 0.001) were found to be significant predictors, but not trabecular BMD ( p = 0.176). For comparison between the two groups, thresholds of all parameters for vertebral fracture were also calculated by the point of coincidence of sensitivity with specificity in ROC testing and the 90th percentile value. Although a rise in fracture threshold in the steroid group was suggested, considerable difference in the values obtained by the two methods of calculation precluded any conclusion. High-dose oral steroid administration was associated with an increased risk of fracture. Cortical bone parameters obtained by pQCT could play a role as good predictors of future corticosteroid-induced vertebral fractures.

MR detection of microhemorrhages in neurologically healthy adults.

T2*-weighted gradient-echo (GE) magnetic resonance images frequently demonstrate small hypointense lesions in patients with systemic hypertension and spontaneous hematomas. These lesions have been suspected to represent subclinical microhemorrhages. We examined the incidence of these lesions in neurologically healthy adults, and the factors associated with them. Axial T2*-weighted GE images (TR = 1,000 ms, TE = 30 ms, flip angle = 20 degrees) were obtained in addition to conventional T1- and T2-weighted spin echo images in 450 neurologically healthy Japanese adults (289 men and 161 women; age 52.9 +/- 7.7 years, range 24-84). The overall incidence of small hypointense lesions was 3.1% (14/450), and these lesions were closely related to systemic hypertension (P < 0.0001) and heavy cigarette smoking (>20 cigarettes per day; P=0.003). Although the incidence of hypointense lesions was lower in neurologically healthy adults than in the reported incidence in patients with a hemorrhagic history, the presence of these lesions was related to the risk factors for primary intracerebral hemorrhage even in the neurologically healthy adults.