An Environmental Change Does Not Affect Dementia Prevalence but Affects Depressive State and Physical Activity: A Trans-Cultural Study of Japanese Elderly Subjects and Japanese Elderly Immigrants in Brazil

Background: Dementia, depressive state, and physical inactivity, are some of the main topics of geriatric medicine. We previously showed the prevalence of dementia in Tajiri, Miyagi Prefecture, Japan. To investigate the environmental effects, first-generation immigrants are one of the best samples. Brazil is the country with the largest number of Japanese immigrants.
Objective: To evaluate the effects of environment on dementia, depressive state, and physical activity, the Tajiri subjects and the elderly Japanese emigrants from Miyagi Prefecture to Brazil were compared.
Methods: The total elderly population in Tajiri and that the elderly members of the Miyagi Association in the São Paulo metropolitan area in Brazil were compared. All data were gathered using a standardized interview covering physical status, cognitive function (Mini-Mental State Examination, MMSE), and depressive state (Self-reported Depressive Scale, SDS). Dementia and depression were diagnosed based on the DSM-IV.
Results: Seventy-six percent of the immigrants perceived their health as being excellent or relatively good, whereas only 56% of Tajiri subjects did so. The percentage of subjects with a history of diabetes mellitus, a lifestyle related disease, was 8.4% in Tajiri and 24.2% in Brazil. In spite of similar prevalences of dementia with slightly different MMSE distributions, the two groups had a different SDS distribution; the immigrants showed lower depressive scores.
Conclusion: In spite of environmental changes influencing physical activity and diabetes, cognitive function was not apparently affected. Although the immigrants lives were marked with hardship, their depressive scores were unexpectedly lower than Japanese, probably due to their stronger mental activity.     

Preventive Care in the Emergency Department: Should Emergency Departments Institute a Falls Prevention Program for Elder Patients? A Systematic Review

OBJECTIVE: To perform a systematic review of the emergency medicine literature to assess the appropriateness of an intervention to identify, counsel, and refer emergency department (ED) patients >64 years old who are at high risk for falls. METHODS: The systematic review was facilitated through the use of a structured template, a companion explanatory piece, and a grading and methodological scoring system based on published criteria for critical appraisal. A reference librarian did two PubMed searches using the following: ED visits, patients >64 years old, falls, high risk, and effectiveness of intervention. Emergency Medical Abstracts, Science Citation Index, and the Cochrane Collaboration database were searched. Two team members reviewed the abstracts and selected pertinent articles. References were screened for additional pertinent articles. RESULTS: Twenty-six articles were reviewed. None were ED-based primary or secondary falls prevention in older patients. One randomized controlled trial of an intervention to decrease subsequent falls in elder community-dwelling patients who presented with a fall showed a structured interdisciplinary approach significantly reducing the number of falls. Two ED-based studies showed it was possible to identify ED patients at risk for falls. CONCLUSIONS: Based on one randomized controlled trial demonstrating a significant reduction in the risk of further falls, the burden of suffering caused by falls, and other studies demonstrating the value of interventions to reduce the risk of falling, the authors recommend that EDs conduct research to evaluate the effectiveness of clinical interventions to identify, counsel, and refer ED patients >64 years old who are at high risk for an unintentional fall.     

Is colorectal cancer screening necessary in the preoperative assessment of inguinal herniorrhaphy? a case-control study

OBJECTIVES: The question of whether patients presenting for inguinal hernia repair require pre-operative assessment for colon cancer has remained unanswered. A case-control study is necessary to assess whether the prevalence of premalignant or malignant colonic lesions is higher in patients presenting with inguinal hernia compared to the general population. METHODS: Between 1990-2000, 614 inguinal herniorrhaphies were performed at the Veterans Affairs Palo Alto Health Care System (VAPAHCS). We retrospectively studied the 149 (24%) patients from this group with no prior history of colonic polyps, malignancy, or gastrointestinal bleeding who had flexible sigmoidoscopy or colonoscopy performed during the peri-operative period. Comparison was made to 149 controls undergoing colonoscopy or sigmoidoscopy during the same time period for colon cancer (CRC) screening. RESULTS: The mean (+/-SEM) patient age was 67 +/- 0.7 (range 31-92) yr in the hernia patients and 66 +/- 0.8 (range 46-93) in the control group (p = 0.7). Eighty-two of the inguinal hernia patients had screening procedures performed preoperatively with a mean time (+/-SEM) of 1.4 +/- 0.14 yr, while endoscopy was performed in the post-operative period for the remaining 67 patients (average time 2.7 +/- 0.2 yr, p < 0.001). More patients underwent colonoscopy in the control group compared to the hernia cohort (p = 0.004). Seven (5%) patients in the hernia group were found to have colorectal cancer compared to six (4%) in the control group (p = 0.8). CONCLUSIONS: This study does not support previously published findings that patients with inguinal hernias are more likely to have premalignant colonic lesions. Patients with inguinal hernias should undergo screening for colon cancer at the same rate as the general population.     

Phase I clinical and pharmacokinetic study of rebeccamycin analog NSC 655649 given daily for five consecutive days.

PURPOSE: Rebeccamycin analog (NSC 655649) is active against a variety of both solid and nonsolid tumor cell lines. We performed a phase I trial to determine the maximum-tolerated dose (MTD) of rebeccamycin analog when given on a daily x 5 schedule repeated every 3 weeks, characterize the toxicity profile using this schedule, observe patients for antitumor response, and determine the pharmacokinetics of the agent and pharmacodynamic interactions. PATIENTS AND METHODS: Thirty assessable patients received a total of 153 cycles according to the following dose escalation schema: 60, 80, 106, 141, and 188 mg/m(2)/d x 5 days. RESULTS: Grade 2 phlebitis occurred in all patients before the use of central venous access, placed at dose level 4 and higher. Dose-limiting toxicity (DLT), grade 4 neutropenia, occurred at 188 mg/m(2)/d x 5 days in both previously treated and chemotherapy-naive patients. Pharmacokinetic analysis revealed a three-compartmental model of drug elimination and a long terminal half-life (154 +/- 55 hours). The percentage drop in absolute neutrophil count correlates with the area under the curve infinity. The presence of a second peak during the elimination phase as well as a high concentration of NSC 655649 in biliary fluid compared with the corresponding plasma measurement (one patient) is suggestive of enterohepatic circulation. Two partial responses, two minor responses, and six prolonged (> 6 months) cases of stable disease were observed. Of these, three patients with gallbladder cancer and one patient with cholangiocarcinoma experienced either a minor response or a significant period of freedom from progression. CONCLUSION: The recommended phase II dose for NSC 665649 on a daily x 5 every 3 weeks schedule is 141 and 165 mg/m(2)/d for patients with prior and no prior therapy, respectively, with DLT being neutropenia. During this phase I trial, encouraging antitumor activity was been observed.     

Geriatric Emergency Medicine Educational Module: Abdominal Pain in the Older Adult

The Society for Emergency Medicine (SAEM) Geriatrics Task Force has created an instructional tool to address the complaint of abdominal pain in older adults presenting to the emergency department (ED). This is the first module in a comprehensive, web-based geriatric emergency medicine curriculum that will address common syndromes in older adults presenting to the ED. There is no formal, residency-based curriculum in geriatric emergency medicine and there is a paucity of geriatric Continuing Medical Education (CME) opportunities for practicing emergency physicians. The amount, quality, and convenience of geriatrics training available to emergency physicians is insufficient. This educational gap is particularly concerning given the ever-growing volume of older adult emergency patients. The Task Force chose to focus first on geriatric abdominal pain because a survey of emergency physicians in the mid 1990s found that it is one of the most difficult complaints to evaluate and manage. The module comprises of six clinical cases with a pre- and post-test. Together, these cases encompass the broad differential diagnosis for geriatric abdominal pain and the core medical knowledge pertaining to the subject. The modules will expose the learner, through either content or modeling, to the six Accreditation Council for Graduate Medical Education (ACGME) core competencies and to the Principles of Geriatric Emergency Medicine including rapid evaluation of functional status, communication skills, and consideration of the effect of polypharmacy and co-morbidity on the presenting complaint. This module will be available to residency programs as an "asynchronous educational session" via the Council of Emergency Medicine Residency Directors (CORD) website as well as to practicing emergency physicians via the SAEM and American College of Emergency Physicians (ACEP) websites.     

Isoflavone, polymorphisms in estrogen receptor genes and breast cancer risk in case-control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians

Epidemiologic studies have shown an inverse association between isoflavones and breast cancer risk. Because isoflavones bind estrogen receptors, we hypothesized that polymorphisms in the estrogen receptor genes might modify the association between isoflavone intake and breast cancer risk. We conducted hospital-based case-control studies of patients aged 20–74 years with primary, incident, histologically confirmed invasive breast cancer, and matched controls from among medical checkup examinees in Nagano, Japan, and from cancer-free patients in São Paulo, Brazil. A total of 846 pairs (388 Japanese, 79 Japanese Brazilians and 379 non-Japanese Brazilians) completed validated food frequency questionnaires, and provided blood samples. Five single nucleotide polymorphisms in the estrogen receptor alpha (rs9340799, rs1913474, and rs2234693) and beta (rs4986938 and rs1256049) genes were genotyped. We found no consistent association between the five single nucleotide polymorphisms and breast cancer risk among the three populations. In analyses of combinations of isoflavone intake and single nucleotide polymorphisms, an inverse association between intake and risk was limited to women with the GG genotype of the rs4986938 polymorphism for postmenopausal Japanese (odds ratio for highest versus lowest tertile = 0.47; P for trend = 0.01), Japanese Brazilians (odds ratio for highest versus lowest median = 0.31) and non-Japanese Brazilians (odds ratio for consumers versus non-consumers = 0.37) ( P for interaction = 0.11, 0.08, and 0.21, respectively). We found no remarkable difference for the other four polymorphisms. Our findings suggest that polymorphisms in the estrogen receptor beta gene may modify the association between isoflavone intake and breast cancer risk. ( Cancer Sci 2009; 100: 927–933)     

Identification of 6-benzylthioinosine as a myeloid leukemia differentiation-inducing compound

As the pathophysiology of acute myelogenous leukemia (AML) involves a block of myeloid maturation, a desirable therapeutic strategy is to induce leukemic cell maturation to increase the efficacy and to avoid the side effects of traditional chemotherapeutics. Through a compound library screen, 6-benzylthioinosine (6BT) was identified as a promising differentiation-inducing agent. 6BT induces monocytic differentiation of myeloid leukemia cell lines such as HL-60 and OCI-AML3, as well as primary patient samples as evidenced by morphology, immunophenotyping, and nitroblue tetrazolium reduction. Not only can 6BT induce differentiation but a subset of AML cell lines such as MV4-11 and HNT34 instead undergo 6BT-mediated cell death. Despite inducing cell death in some leukemic cells, 6BT exhibits extremely low toxicity on several nonmalignant cells such as fibroblasts, normal bone marrow, and endothelial cells. This toxicity profile may relate to the function of 6BT as an inhibitor of the nucleoside transporter, ent1, which is thought to prevent it from entering many cell types. In contrast, 6BT likely enters at least some leukemic cell lines as shown by its requirement for phosphorylation for its differentiation activity. 6BT is also able to synergize with currently used myeloid differentiation agents such as ATRA and decitabine. Early studies indicate that the mechanism of action of this compound may involve ATP depletion that leads to growth inhibition and subsequent differentiation. Besides in vitro activity, 6BT also shows the ability to impair HL-60 and MV4-11 tumor growth in nude mice. 6BT is a promising new monocytic differentiation agent with apparent leukemic cell-specific activity.     

Dual MET�CEGFR combinatorial inhibition against T790M-EGFR-mediated erlotinib-resistant lung cancer

Despite clinical approval of erlotinib, most advanced lung cancer patients are primary non-responders. Initial responders invariably develop secondary resistance, which can be accounted for by T790M-EGFR mutation in half of the relapses. We show that MET is highly expressed in lung cancer, often concomitantly with epidermal growth factor receptor (EGFR), including H1975 cell line. The erlotinib-resistant lung cancer cell line H1975, which expresses L858R/T790M-EGFR in-cis, was used to test for the effect of MET inhibition using the small molecule inhibitor SU11274. H1975 cells express wild-type MET, without genomic amplification (CNV=1.1). At 2 μM, SU11274 had significant in vitro pro-apoptotic effect in H1975 cells, 3.9-fold (P=0.0015) higher than erlotinib, but had no effect on the MET and EGFR-negative H520 cells. In vivo, SU11274 also induced significant tumour cytoreduction in H1975 murine xenografts in our bioluminescence molecular imaging assay. Using small-animal microPET/MRI, SU11274 treatment was found to induce an early tumour metabolic response in H1975 tumour xenografts. MET and EGFR pathways were found to exhibit collaborative signalling with receptor cross-activation, which had different patterns between wild type (A549) and L858R/T790M-EGFR (H1975). SU11274 plus erlotinib/CL-387,785 potentiated MET inhibition of downstream cell proliferative survival signalling. Knockdown studies in H1975 cells using siRNA against MET alone, EGFR alone, or both, confirmed the enhanced downstream inhibition with dual MET–EGFR signal path inhibition. Finally, in our time-lapse video-microscopy and in vivo multimodal molecular imaging studies, dual SU11274-erlotinib concurrent treatment effectively inhibited H1975 cells with enhanced abrogation of cytoskeletal functions and complete regression of the xenograft growth. Together, our results suggest that MET-based targeted inhibition using small-molecule MET inhibitor can be a potential treatment strategy for T790M-EGFR-mediated erlotinib-resistant non-small-cell lung cancer. Furthermore, optimised inhibition may be further achieved with MET inhibition in combination with erlotinib or an irreversible EGFR-TKI.     

Genetic diversity and antifungal susceptibility of Fusarium isolates in onychomycosis

Fusarium species have emerged as an important human pathogen in skin disease, onychomycosis, keratitis and invasive disease. Onychomycosis caused by Fusarium spp. The infection has been increasingly described in the immunocompetent and immunosuppressed hosts. Considering onychomycosis is a difficult to treat infection, and little is known about the genetic variability and susceptibility pattern of Fusarium spp., further studies are necessary to understand the pathogenesis and better to define the appropriate antifungal treatment for this infection. Accordingly, the objective of this study was to describe the in vitro susceptibility to different antifungal agents and the genetic diversity of 35 Fusarium isolated from patients with onychomycosis. Fusarium spp. were isolated predominantly from female Caucasians, and the most frequent anatomical location was the nail of the hallux. Results revealed that 25 (71.4%) of isolates belonged to the Fusarium solani species complex, followed by 10 (28.5%) isolates from the Fusarium oxysporum species complex. Noteworthy, the authors report the first case of Neocosmospora rubicola isolated from a patient with onychomycosis. Amphotericin B was the most effective antifungal agent against the majority of isolates (60%, MIC ≤4 μg/mL), followed by voriconazole (34.2%, MIC ≤4 μg/mL). In general, Fusarium species presented MIC values >64 μg/mL for fluconazole, itraconazole and terbinafine. Accurate pathogen identification, characterisation and susceptibility testing provide a better understanding of pathogenesis of Fusarium in onychomycosis.     

Interrelationship of mmpi-2 validity scales in personal injury claims

A sample of MMPI-2s of worker's compensation and personal injury cases (N = 289) was gathered to examine the relationship of various indicators of exaggeration. Intercorrelations of the F, F - K, the MMPI Dissimulation Scale-revised (Ds-r), total of obvious minus subtle scales (O - S), Fake Bad Scale (FBS), VRIN, and TRIN were computed and the relative sensitivity of each score calculated using various cut-offs. Factor analysis suggests that malingering may take the form of inconsistent responding as well as symptom exaggeration. Patients evaluated at the request of plaintiff attorneys showed a seemingly greater degree of symptom exaggeration and inconsistent responding than did those referred by defense counsel.