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M Sano

Publications and source records attributed to M Sano.

At least 199 records · Page 11Linked to original sources

Assessing patterns of agitation in Alzheimer's disease patients with the Cohen-Mansfield Agitation Inventory. The Alzheimer's Disease Cooperative Study.

As part of the effort of the NIA Alzheimer's disease cooperative study to develop improved instruments for quantifying effects in Alzheimer's disease (AD) clinical trials, patterns of agitated behaviors were evaluated with the Cohen-Mansfield Agitation Inventory (CMAI) in 241 AD patients and 64 healthy elderly controls with valid baseline assessment on the CMAI. The test-retest reliability of the CMAI over 1 month was good (r = 0.74 to 0.92). Physically and verbally nonaggressive behaviors were most often reported, whereas physically aggressive behaviors were rare. Frequency of agitated behaviors increased with dementia severity, especially for patients with a Mini-Mental Status Exam score of 0-4. Agitation tended to increase in the evening with dementia severity for the more impaired patients. Amount of agitation did increase after 12 months in all but controls and mildly demented patients. The CMAI shows promise for evaluating a unique aspect of behavior and may be useful in assessing the effects of cognitive enhancers and other types of psychotropic drugs on behavior in dementia patients.

Aged↗

Antitumor activity of a novel quinoline derivative, TAS-103, with inhibitory effects on topoisomerases I and II.

A novel quinoline derivative, TAS-103 (6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-indeno[2,1-c]quinolin -7-one dihydrochloride), was developed as an anticancer agent targeting topoisomerases (topo) I and II, with marked efficacy in solid tumors. TAS-103 inhibited topo I and II (IC50: 2 microM, 6.5 microM) at a concentration similar to or lower than those of previous agents, and had a strong cytotoxic effect on P388 and KB cells (IC50: 0.0011 microM, 0.0096 microM). TAS-103 stabilized topo I and II-DNA cleavable complexes in KB cells, generating a similar amount of topo II-DNA complex to that induced by etoposide (VP-16) but a smaller amount of topo I-DNA complex than that produced by camptothecin (CPT). In the in vivo study, intermittent i.v. administration was markedly effective against s.c.-implanted murine tumors. Furthermore, TAS-103 had marked efficacy against various lung metastatic tumors, and a broad antitumor spectrum in human tumor xenografts (derived from lung, colon, stomach, breast, and pancreatic cancer). The efficacy of TAS-103 was generally greater than that of irinotecan (CPT-11), VP-16, or cis-diamminedichloroplatinum (CDDP).

Adenocarcinoma↗

Decrease of prostaglandin E2 and 5-bromo-2'-deoxyuridine labeling but not prostate tumor development by indomethacin treatment of rats given 3,2'-dimethyl-4-aminobiphenyl and testosterone propionate.

The modifying effects of indomethacin (IM) on rat prostate carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB) were investigated. F344 rats were given 50 mg/kg body weight of DMAB at 2-week intervals for 20 weeks and then received IM at a dose of 20 ppm in the drinking water for 37 weeks. Separate groups additionally received testosterone propionate (TP) in Silastic tubes throughout the experiment. DMAB alone induced carcinomas in situ in the ventral lobe and in combination with TP caused invasive carcinomas of the dorso-lateral and anterior lobes and seminal vesicles. No clear suppression by IM of development of in situ carcinomas or invasive carcinomas was observed. In a short-term satellite experiment, it was revealed that prostaglandin E2 (PGE2) levels in the dorso-lateral prostate and seminal vesicles, but not the ventral prostate, were significantly reduced by IM and that TP itself also suppressed PGE2 levels. The 5-bromo-2'-deoxyuridine labeling index in the ventral prostate was significantly decreased by IM administration. These results indicate that while IM can efficiently suppress tissue PGE2 levels, it does not inhibit tumor development in the prostate or seminal vesicles of rats in the present model.

Aminobiphenyl Compounds↗

Alzheimer's disease after remote head injury: an incidence study.

OBJECTIVE: To evaluate a history of remote head injury as a risk factor for subsequent dementia due to Alzheimer's disease. METHODS: 271 participants of a community based longitudinal study of aging in north Manhattan without evidence of significant cognitive impairment were interrogated for a history of head injury on two occasions at entry into the study. The examining physician sought a history of head injury with loss of conciousness. Independently, a risk factor interviewer inquired about a history of head injury with loss of consiousness or amnesia, the duration of any loss of consiousness, and the date of the head injury. Patients were followed up with standardised annual evaluations for up to five years to determine the first occurrence of dementia. RESULTS: Over the course of the study incident dementia due to probable or possible Alzheimer's disease was diagnosed in 39 patients. Cox proportional hazards modelling showed that a history of head injury with loss of consiousness reported to the physician was associated with earlier onset of dementia due to Alzheimer's disease (relative risk (RR) = 4.1, 95% confidence interval (95% CI) 1.3-12.7). head injury with loss of consiousness or amnesia reported to the risk factor interviewer was not significantly associated with earlier onset of Alzheimer's disease overall (RR 2.0, 95% CI 0.7-6.2), but those who reported loss of consiousness exceeding five minutes were at significantly increased risk (RR 11.2, 95% CI 2.3-59.8). Incident Alzheimer's disease was significantly associated with head injury which occurred within the preceding 30 years (RR 5.4, 95% CI 1.5-19.5). CONCLUSION: The results of this cohort study are consistent with the findings of several case-control studies suggesting that head injury may be a risk factor for Alzheimer's disease.

Age of Onset↗

Role of angiotensin II in activation of the JAK/STAT pathway induced by acute pressure overload in the rat heart.

This study was designed to determine whether the JAK/STAT (indicating just another kinase/signal transducer and activator of transcription) pathway is activated in cardiac hypertrophy induced in vivo by pressure overload in rats and to demonstrate whether angiotensin II is involved in the activation of the JAK/STAT pathway. Acute pressure overload was produced by constricting the abdominal aorta of Wistar rats. Immunoprecipitation-Western blot analysis revealed that pressure overload activated JAK1, JAK2, and Tyk2 as early as 5 minutes and that STAT1, STAT2, and STAT3 were tyrosine-phosphorylated rapidly after exposure to the pressure overload. Phosphorylation of STAT1 and STAT2 peaked in the early stage at 5 to 15 minutes, whereas that of STAT3 peaked in the late stage at 60 minutes. Gel mobility shift of the interferon gamma activation site/interferon alpha-stimulating response element was observed immediately after the aortic banding, whereas the band of sis-inducing element was shifted in the late stage at 60 minutes. Both cilazapril (angiotensin II-converting enzyme inhibitor) and E4177 (angiotensin II type 1 [AT1] receptor antagonist) significantly suppressed the phosphorylation of Tyk2 and partially inhibited the phosphorylation of JAK2, but neither affected JAK1. Coimmunoprecipitation of the AT1 receptor with JAK2 or Tyk2 was clearly observed at 5 minutes and peaked at 15 minutes (20-fold the control value). These results indicate that the JAK/STAT pathway is activated by acute pressure overload in rats and that angiotensin II is involved in activating Tyk2, and partially activating JAK2, via the AT1 receptor. Both angiotensin II-dependent and -independent pathways take part in activating the JAK/STAT pathway in the pressure-overloaded rat heart.

Acute Disease↗

Association of subjective memory complaints with subsequent cognitive decline in community-dwelling elderly individuals with baseline cognitive impairment.

OBJECTIVE: The validity of subjective memory complaints has been questioned by clinical studies that have shown little relationship between memory complaints and objective memory performance. These studies often have been cross-sectional in design, have excluded individuals with cognitive impairment, or have lacked a comparison group. The authors conducted a study that attempted to avoid these limitations. METHOD: Memory complaints of 364 nondemented, community-dwelling elderly individuals were recorded as present or absent at the baseline evaluation. After 1 year, 169 subjects were reevaluated. Standardized neurologic and neuropsychological evaluations were used at each assessment to classify subjects as normal or cognitively impaired. RESULTS: At baseline, 31% of the normal subjects and 47% of those with cognitive impairment had memory complaints. Subjects with memory complaints had higher Hamilton depression scale scores than subjects without memory complaints but equivalent scores on a measure of total recall. At follow-up, multivariate analyses showed that subjects with baseline memory complaints had significantly greater decline in memory and cognition than subjects without memory complaints. Secondary analyses showed this effect to be confined to subjects with baseline cognitive impairment. CONCLUSIONS: Memory complaints may lack validity in subjects with normal cognition, but in nondemented individuals with cognitive impairment, memory complaints may predict subsequent cognitive decline.

Aged↗

Clinical dementia rating training and reliability in multicenter studies: the Alzheimer's Disease Cooperative Study experience.

Global ratings of dementia severity are used increasingly in clinical trials of antidementia compounds. Such ratings are clinically relevant, but their reliability in multicenter settings has not been determined. To evaluate the reliability of one global scale, the Clinical Dementia Rating (CDR), 82 investigators of the multicenter Alzheimer's Disease Cooperative Study participated in a training and reliability protocol using videotaped assessments of subjects in various stages of Alzheimer's disease. Following training, overall agreement of the investigators with "gold standard" CDR scores was 83%. These results indicate that the training protocol is useful for establishing good levels of agreement in staging dementia severity and that the CDR can be standardized as a clinical global scale for multicenter studies of Alzheimer's disease.

Alzheimer Disease↗

Participation in clinical trials and long-term outcomes in Alzheimer's disease.

The objective of this study was to determine whether participation in clinical trials affects long-term outcomes in Alzheimer's disease (AD). Participation in clinical trials for persons with dementia is often justified on the grounds that patients benefit from the medical oversight typical of trials, even when experimental agents do not demonstrate short-term benefits. This claim has not been rigorously assessed. Of 215 community-resident subjects enrolled in a prospective study of outcomes in AD, 101 participated in randomized clinical trials (RCTs) during the first 2 years of follow-up. These subjects were compared with subjects who met eligibility requirements for RCTs but did not participate (N = 57) and with subjects who were ineligible (N = 57), over a total of 3.5 years of follow-up. Survival analyses assessed risk of death, nursing home placement, and incident functional deficit end points, adjusting for baseline differences. Subjects who participated in RCTs were younger and more highly educated. Mortality, risk of hospitalization, number of medical examinations conducted by study physicians, and onset of severe functional deficit did not differ between the groups, but risk of nursing home admission was significantly lower among RCT participants compared with eligible nonparticipants and ineligible subjects (16.8% versus 36.8% and 31.6%, respectively [p = 0.01]). The difference in risk of nursing home placement may represent a long-term, drug-related benefit to patients, a selection effect (caregivers of patients who participate in RCTs differ from caregivers of patients who do not), or a positive effect on caregivers (greater contact with a medical service may be associated with better care-giving outcomes). Further research is required to assess these effects.

Aged↗

[Studies on antioxidant effect of Hypsizigus marmoreus. I. Effects of Hypsizigus marmoreus for antioxidant activities of mice plasma].

The antioxidant effects of Hypsizigus marmoreus, one of the most popular Japanese edible mushrooms, were investigated by the use of the augmentation effect of antioxidant activity (AOA) in the mice plasma. An aqueous extract of the mushroom fruit-body was found to have a slight trap activity for peroxyl and alkoxyl radicals. On the other hand, the blood plasma of mice fed with a fodder containing 5-10% of the dried powder of the mushroom extract augmented significantly AOA for alkoxyl radicals. It was suggested from analysis of the plasma by the HPLC post column AOA method that the increase of AOA in the mice plasma was caused by the induction of high molecular weight fractions having AOA produced by feeding Hypsizigus marmoreus. The amount of lipoperoxide in the mice plasma as values of thiobarbituric acid reactive substances showed a tendency to be lowered by intake of Hypsizigus marmoreus. These results suggest that oral administration of the fruit-body of Hypsizigus marmoreus can induce an antioxidant effect in the mice plasma.

Administration, Oral↗

Facial nerve enhancement on gadolinium-DTPA in a case with neurosarcoidosis.

In a case of neurosarcoidosis with bilateral facial nerve palsy and hydrocephalus, contrast-enhanced magnetic resonance imaging (MRI) study and angiotensin converting enzyme (ACE) activities in cerebrospinal fluid (CSF) were valuable for the diagnosis and the follow up. Facial nerve lesions were demonstrated on gadolinium-DTPA enhanced MRI. The disappearance of enhancement was concomitant with the amelioration of facial nerve palsy after corticosteroid therapy.

Adult↗

[A clinical study on combination therapy of antimicrobial agents for complicated urinary tract infection--with special reference to combination with clarithromycin].

PURPOSE: To confirm the clinical efficacy of the combined therapy to complicated urinary tract infection (UTI), we conducted a comparative clinical study of the combined therapy with ciprofloxacin (CPFX) and clarithromycin (CAM) acting an biofilm elimination or CPFX alone in patients with complicated UTI. PATIENTS AND METHODS: The study was carried out in patients with complicated UTI having WBCs with 5/hpf or more in urinary sediment and bacteriuria at least 10(4) CFU/ml. The combined therapy was CPFX and CAM, each 600 mg/day, for 14 days, and the single therapy group CPFX, 600 mg/day, for 14 days. On Day 7 and 14, the eradication rate and efficacy rate (according to the criteria of the Japanese UTI committee) were determined. In the patients with indwelling catheter, the surface of the catheter tip was observed under a scanning electron microscope (SEM) on Day 14. RESULTS: In both cases with and without catheters, clinical efficacy was higher in the combined therapy group than in the single therapy group. In particular, the efficacy rates at 14 Day were significantly higher in the former group. Furthermore, we investigated the therapeutic effect in the below MIC breakpoint of CPFX in complicated UTI. The combined therapy group showed a higher clinical efficacy in both cases with and without indwelling catheter than the single therapy group, although there was not statistically significant. Biofilm on the surface of the catheter tip was eliminated in 75% of the combined therapy group. However, none of the biofilm was eliminated in the single therapy group. CONCLUSION: From the above results, we surmise that the combined use of CPFX and CAM will show some degree of efficacy in eliminating both the causative organism and its biofilm in the complicated UTI.

Adult↗

[Helical CT of the breast: detection of intraductal spread and multicentricity of breast cancer].

PURPOSE: This study was performed to evaluate the clinical utility of postcontrast helical CT (HCT) scan for the detection of intraductal spread (DS) and multicentricity of breast cancer. MATERIALS AND METHODS: DS and multicentricity in 84 patients with invasive ductal carcinoma were evaluated by preoperative postcontrast HCT. The HCT protocol of 3-mm section width and 3 mm/sec table speed was used with the patients in a supine position. Scanning started 70sec after beginning the intravenous injection of 90 ml (27 gI) of contrast material at the rate of 1.5 ml/sec. The three-dimensional images were displayed. RESULTS: Eighty-four of 84 main tumors (100%) were shown as enhanced masses by postcontrast HCT. The sensitivity and specificity of HCT for the detection of DS and multicentricity were 60.0% (18/30) and 88.9% (48/54), and 88.9% (16/18) and 90.9% (60/66), respectively. When DS and multicentric lesions were combined, the sensitivity and the specificity were 76.3% (29/38) and 89.1% (41/46), respectively. CONCLUSION: HCT of the breast is effective in detecting DS and multicentric lesions of breast cancer and might be useful in helping surgeons to successfully perform breast-conserving surgery.

Adult↗

[Echocardiographic evaluation of cardiotoxicity induced by anthracycline therapy].

Echocardiographic reports on 144 adults receiving anthracycline therapy and 18 controls were reviewed for the possible relationship between dosage and ejection fractions. The cardiotoxicity of each anthracycline drug was evaluated as follows: Pirarubicin = 0.8, Mitoxantrone = 3.4, Daunorubicin = 0.5, Aclarubicin = 0, and Epirubicin = 0.6 with Doxorubicin = 1 as a control. As a whole, the ejection fractions, which decreased subsequently compared with increasing amount of dosage, showed a remarkable decrease at the dosage level of 600 mg/m2. However, the ejection fractions differed among individual patients. It was predicted that heart failure would not develop when the ejection fractions exceeded 55%. It is desirable to stop anthracycline therapy when the ejection fractions drop to 55%.

Aclarubicin↗

A multicenter evaluation of new treatment efficacy instruments for Alzheimer's disease clinical trials: overview and general results. The Alzheimer's Disease Cooperative Study.

Evaluating treatment efficacy in Alzheimer's disease (AD) clinical trials requires optimal assessment methods to determine the extent and clinical meaningfulness of potential therapeutic effects of pharmacologic agents. Development of improved outcome measures for AD clinical trials is a major objective of the Alzheimer's Disease Cooperative Study (ADCS), an NIA-sponsored, multisite clinical trials consortium. The ADCS Instrument Development Project evaluated the sensitivity, reliability and validity of new or improved measures in each of five assessment domains: (a) cognition (immediate and delayed memory, praxis, attention, and executive function); (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms (agitation and other noncognitive symptoms); and (e) cognition in severely impaired patients. A total of 306 English-speaking subjects were enrolled in the study, including AD patients stratified by disease severity and cognitively normal, age-matched elderly subjects. Half were retested at 1 month and 2 months after baseline, and all received 6- and 12-month follow-up assessments. Spanish versions of these new measures are currently being evaluated. The development of this multisite study, the common methods and procedures, and a detailed description of the cohort are provided in this overview article. This multisite project demonstrates the feasibility of a consortium approach to instrument development. We were able to develop new instruments and efficiently evaluate their reliability and sensitivity to longitudinal change by capitalizing on the experience and patient resources of the participating ADCS research sites.

Aged↗

Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's Disease Assessment Scale that broaden its scope. The Alzheimer's Disease Cooperative Study.

The cognitive assessment protocol of the Alzheimer's Disease Cooperative Study (ADCS) was designed to evaluate the reliability and validity of cognitive assessment measures that might be valuable additions to the Alzheimer's Disease Assessment Scale (ADAS) or other concise batteries used in antidementia drug trials. As part of an overall ADCS protocol to develop new instruments to be used in trials of treatments for Alzheimer's disease (AD), patients with mild to moderate AD and cognitively normal elderly were administered a battery of five tests at least three times over 1 year. The tests included word list learning with delayed free recall, a recognition memory test for faces, a series of letter and digit cancellation tests to measure concentration, tests of praxis, and a series of maze completion tasks designed to assess planning and executive function. A version of the digit cancellation task was reliable and sensitive to a broad range of dementia severity so that it could provide a useful addition to the present version of the ADAS. Performance on the word learning task with delayed recall and a subset of the mazes task were impaired even in mild AD, so these tasks may be useful in trials involving mild or at-risk subjects. Performances on the facial recognition task and on the praxis tasks were not related to dementia severity, so these tasks would not be useful to evaluate treatments. Therefore, the major outcome of this investigation was the identification of some potential additions to the present ADAS that extend both the cognitive domains and the range of symptom severity covered.

Aged↗

An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

We developed a set of informant-based items describing performance of activities of daily living (ADL) by patients with Alzheimer's disease (AD) to identify which ADL are useful for assessment of patients in clinical trials. Evaluation of ADL is an important outcome measure in AD clinical trials. For clinical trial measurement, ADL should have broad applicability, good test-retest reliability, scaling to cover a range of performance, and sensitivity to detect change in disease progression. A total of 45 ADL items developed from literature review and clinical experience were administered to informants of 242 AD patients and 64 elderly controls as part of the multicenter Alzheimer's Disease Cooperative Study Instrument protocol. Half of the subjects were re-evaluated at 1 and 2 months and all at 6 and 12 months. Controls performed virtually all ADL items optimally at baseline and at 12 months. Among subjects with AD, 27 of the 45 ADL were widely applicable, i.e., performed at baseline or premorbidly by > 90% of subjects; showed good test-retest reliability between baseline and 1 and 2 months; correlated with MMSE scores of AD patients cross-sectionally; and showed a decline in performance from baseline to 12 months in at least 20% of AD patients. ADL could be identified that capture change in functional ability in patients across the entire range of the MMSE. The remaining 18 ADL included several that may be useful for trials that target specific populations, e.g., women with AD. Because change on specific items depends on baseline MMSE, ADL evaluation should include items relevant to the severity of dementia of patients enrolled in a clinical trial.

Activities of Daily Living↗

The Spanish Instrument Protocol: design and implementation of a study to evaluate treatment efficacy Instruments for Spanish-speaking patients with Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

Development of improved outcome measures for Alzheimer's disease (AD) clinical trials is a major objective of the Alzheimer's Disease Cooperative Study (ADCS), an NIA-sponsored, multisite clinical trials consortium. The ADCS is committed to recruiting and following minority patients in clinical trials. At present, a serious impediment to recruiting non-English-speaking minorities is the lack of instruments with adequate translation. Because Spanish is the second most commonly spoken language in the United States and because persons of Hispanic origin represent approximately 10% of the population, we conducted an instrument development protocol for Spanish-speaking patients. Evaluating treatment efficacy in Spanish-speaking AD patients requires the development of assessments that are comparable to those used for English-speaking participants in clinical trials. The ADCS Instrument Development Project evaluated the sensitivity, reliability, and validity of new or improved measures in each of five assessment domains: (a) cognition (immediate and delayed memory, praxis, attention, and executive function); (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms (agitation and other noncognitive symptoms); and (e) cognition in severely impaired patients. These new treatment efficacy instruments were translated for Spanish speakers and a Spanish Instrument Study was conducted in parallel with the English version of the study. This report describes instrument translation, entry criteria, and recruitment procedures. In addition, the demographic and clinical characteristics of the cohort at baseline are presented and compared to the English-speaking cohort. Implications for the development of comparably sensitive Spanish language instruments are discussed.

Aged↗