Geriatric nutritional risk index as the prognostic factor in older patients with fragility hip fractures.

This study investigated the long-term survival and incidence of secondary fractures after fragility hip fractures. The 5-year survival rate was 62%, and the mortality risk was seen in patients with GNRI < 92. The 5-year incidence of secondary fracture was 22%, which was significantly higher in patients with a BMI < 20. BACKGROUND: Malnutrition negatively influences the postoperative survival of patients with fragility hip fractures (FHFs); however, little is known about their association over the long term. OBJECTIVE: This study evaluated the ability of the geriatric nutritional risk index (GNRI) as a risk factor for long-term mortality after FHFs. METHODS: This study included 623 Japanese patients with FHFs over the age of 60 years. We prospectively collected data on admission and during hospitalization and assessed the patients' conditions after discharge through a questionnaire. We examined the long-term mortality and the incidence of secondary FHFs and assessed the prognostic factors. RESULTS: The mean observation period was 4.0 years (range 0-7 years). The average age at the time of admission was 82 years (range 60-101 years). The overall survival after FHFs (1 year, 91%; 5 years, 62%) and the incidence of secondary FHFs were high (1 year, 4%; 5 years, 22%). The multivariate Cox proportional hazard analysis revealed the risk factors for mortality as older age (hazard ratio [HR] 1.04), male sex (HR 1.96), lower GNRI score (HR 0.96), comorbidities (malignancy, HR 2.51; ischemic heart disease, HR 2.24; revised Hasegawa dementia scale ≤ 20, HR 1.64), no use of active vitamin D3 on admission (HR 0.46), and a lower Barthel index (BI) (on admission, HR 1.00; at discharge, HR 0.99). The GNRI scores were divided into four risk categories: major risk (GNRI, < 82), moderate risk (82-91), low risk (92-98), and no risk (> 98). Patients at major and moderate risks of GNRI had a significantly lower overall survival rate (p < 0.001). Lower body mass index (BMI) was also identified as a prognostic factor for secondary FHFs (HR 0.88 [p = 0.004]). CONCLUSIONS: We showed that older age, male sex, a lower GNRI score, comorbidities, and a lower BI are risk factors for mortality following FHFs. GNRI is a novel and simple predictor of long-term survival after FHFs.

Evaluation of skin cancer chemoprevention potential of sunscreen agents using the Epstein-Barr virus early antigen activation in vitro assay.

In our continuing search for novel cancer chemopreventive compounds of natural and synthetic origin, we have evaluated 14 commonly used ultraviolet (UV) sunscreen agents (designated UV-1 to UV-14) for their skin cancer chemoprevention potential. They belong to 8 different chemical categories: aminobenzoate (UV-5, UV-7, UV-8 and UV-14), benzophenone (UV-1, UV-2, UV-3 and UV-13), benzotriazole (UV-10), benzyloxyphenol (UV-9), cinnamate (UV-6), quinolone (UV-4), salicylate (UV-11) and xanthone (UV-12). In the in vitro assay employed, the sunscreens were assessed by their inhibition of the Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in human lymphoblastoid Raji cells. All sunscreens tested were found to exhibit anti-tumour promoting activity: listed in decreasing order, moderate (UV-11, UV-2, UV-7, UV-12, UV-3, UV-9 and UV-14) to weak (UV-1, UV-6, UV-8, UV-16, UV-5, UV-4 and UV-10) with octyl salicylate (UV-11) as the most potent and drometrizole (UV-10) as the least potent among the compounds evaluated. A plausible relationship between the antioxidant property of sunscreens and their ability to promote anti-tumour activity was noted. The results call for a comprehensive analysis of skin cancer chemoprevention potential of currently used UV sunscreen agents around the globe to identify those with the best clinical profile.

Revascularization by percutaneous transluminal angioplasty improved abruptly deteriorated ischaemic symptoms in cutaneous polyarteritis nodosa.

We report a patient with cutaneous polyarteritis nodosa, who had a 3-year history of recurrent leg and foot ulcers. Symptoms of ischaemia in the left foot, including severe pain, coldness, paraesthesia and violaceous discoloration, deteriorated abruptly, because of complete occlusion of the left anterior tibial artery. The occluded segment was revascularized by percutaneous transluminal angioplasty, resulting in a dramatic improvement in the ischaemic symptoms.

Cancer chemopreventive activity of diversin from Ferula diversivittata in vitro and in vivo.

A prenylated coumarin (diversin, 1) together with four new sesquiterpene lactones (diversolides A, D, F and G, 2-5) isolated from the roots of Ferula diversivittata were studied for their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). All of the tested compounds were active against EBV-EA activation. Among these compounds diversin (IC(50): 7.7) exhibited the strongest inhibitory effect and was selected to examine its effects on in vivo two-stage mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and TPA as promoter. Treatment with compound 1 (85nmol) along with DMBA/TPA inhibited papilloma formation up to week 7 and the percentage of papilloma bearers was approximately 93.3% at week 20. The average number of papillomas formed per mouse was only 5.5 even at week 20. The results of the present investigation indicated that diversin might be valuable as a potent cancer chemopreventive agent and its potency was comparable with those of curcumin and quercetin, two well-known cancer chemopreventive agents.

Asymptomatic myocardial ischemia in relation to carotid artery stenosis among patients with aortic aneurysm.

AIM: The prevalence of asymptomatic coronary artery stenosis in relation to carotid artery stenosis is influenced by the underlying disease and has yet to be clarified. METHODS: A total of 124 consecutive Japanese patients with aortic aneurysm, but without symptoms of coronary artery stenosis, were divided into 2 groups on the basis of carotid ultrasonography: the carotid stenosis group (>or=50% luminal diameter narrowing) and the non-stenosis group. Myocardial imaging was performed using thalium-201 chloride and adenosine triphosphate disodium. RESULTS: The mean age and incidence of both cerebrovascular disease and peripheral artery disease were significantly higher in the stenosis group (n=24) than the non-stenosis group (n=100). Defining both fixed and reversible hypoperfusion as positive on the basis of myocardial imaging, a significantly higher number of positive findings were found in the stenosis group (15/24; 62.5%) than in the non-stenosis group (32/100, 32.0%), (Odds ratio: 3.54; p<0.01). The distributions of hypoperfusion defects in the stenosis group were similar to those in the non-stenosis group, but fixed hypoperfusion was more frequently seen in the stenosis group. CONCLUSION: The high prevalence of positive findings in the stenosis group indicates that carotid artery stenosis is frequently associated with coronary artery stenosis even in asymptomatic patients, and could be an indicator for advanced atherosclerosis of the coronary artery. The results confirm that stress myocardial imaging is invaluable in the detection of coronary artery stenosis, particularly in patients with carotid arteriosclerosis.

Antitumor activity of a phenoxazine compound, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one against human B cell and T cell lymphoblastoid cell lines: induction of mixed types of cell death, apoptosis, and necrosis.

PURPOSE: We studied the antitumor activity of 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx), which was synthesized by the reactions of 2-amino-5-methylphenol with bovine hemoglobin, on human B cell lymphoblastoid cell lines, P3HR-1 and Raji derived from African Burkitt's lymphoma, and the human T cell lymphoblastoid cell line Molt-4. We also studied whether Phx might cause apoptosis and necrosis in these cells. METHODS: We evaluated cell viability and apoptosis and necrosis of the cells in the presence of Phx, by using agarose gel electrophoresis, flow cytometry, and fluorescence microscopy. RESULTS: Phx suppressed the viability of P3HR-1, Raji, and Molt-4 cells, though the suppression patterns were different, i.e., Phx suppressed the viability of P3HR-1, Raji, and Molt-4 cells at higher concentrations, while the drug enhanced the viability of Raji cells, but not those of P3HR-1 and Molt-4 cells at lower concentrations. To investigate which type of cell death - apoptosis or necrosis - is induced by Phx, induction of DNA ladder, phosphatidylserine externalization, and propidium iodide-permeable cells were examined in Phx-treated cells. Although Phx did not induce DNA ladder formation, it induced the phosphatidylserine externalization and propidium iodide-permeable cells, suggesting that Phx caused a mixed type of cell death, both apoptosis and necrosis. The population of early stage apoptotic cells was dominant in Raji cells, and that of the late stage apoptotic/necrotic cells was dominant in Molt-4 cells after 72-h treatment with Phx. The population of the early stage apoptotic cells and the late stage apoptotic/necrotic cells was almost equal in P3HR-1 cells in the presence of Phx, though the population of both types of cells increased with time. The nuclear morphological analysis of Phx-treated Raji, P3HR-1, and Molt-4 cells also showed that Phx induces apoptosis. CONCLUSIONS: The present results suggest that Phx shows antitumor activity against human B cell-derived and T cell-derived lymphoblastoid cell lines, in vitro, causing apoptosis and necrosis.

The characterization of bronchoalveolar lavage fluid in very elderly patients with cerebrovascular disease.

BACKGROUND: Elderly patients with cerebrovascular disease have a high frequency of pneumonia due to impaired immune function and the occurrence of micro-aspiration. METHODS: We performed bronchoalveolar lavage in 11 very elderly subjects with cerebrovascular disease and 9 healthy volunteers to investigate whether there were changes of local immunity in the lungs of the elderly subjects. The total cell count, the cell characteristics, and the lymphocyte subsets in bronchoalveolar lavage fluid were compared between the two groups. RESULTS: A significant increase in the total cell count as well as in the number of neutrophils and CD8(+) T cells was observed in the elderly group. In addition, the mean CD4/CD8 lymphocyte ratio was lower in the elderly patients than in the healthy volunteers. CONCLUSIONS: These observations suggest that silent micro-aspiration occurs in many elderly individuals with cerebrovascular disease and that pulmonary defenses decrease with age.

Intrathecal pre-administration of fentanyl effectively suppresses formalin evoked c-Fos expression in spinal cord of rat.

PURPOSE: To investigate whether the timing of intrathecal administration of the opioid analgesic fentanyl, alters noxious stimulus-evoked neuronal activity in the rat spinal cord. METHODS: A 5% formalin solution was used as the noxious stimulant. For the pretreatment group, a dose of 0.001 to 0.5 microg of fentanyl was injected intrathecally ten minutes prior to formalin injection. Early and late post-treatment groups received 0.01 to 0.5 microg fentanyl, five and 60 min after formalin injection respectively. The effect of fentanyl was confirmed with naloxone. The level of c-Fos expression was determined in each treatment group to indicate neuronal activity. RESULTS: Pretreatment and early post-treatment groups showed suppression of c-Fos activity compared to the vehicle (P <0.01). The late post-treatment group showed no difference in c-Fos activity compared to the vehicle (P=NS). Pretreatment with fentanyl showed the most profound suppression of c-Fos expression (P <0.01). In addition, pretreatment injection showed a greater suppression of c-Fos activity in the deep (14.6% of control) compared to the superficial laminae (32.7% of control; P <0.01), whereas the early post-treatment group showed a universal decrease in c-Fos activity (49.2% of control in laminae I and II, 50.4% of control in laminae III and IV and 51.8% of control in laminae V and VI). Naloxone reversed the action of fentanyl on c-Fos activity. CONCLUSION: Inasmuch as: 1) c-Fos expression can be equated with behavioural changes; 2) injection of formalin is an appropriate model of surgical trauma; and 3) animal data can be transports to humans, these results suggest that fentanyl would be an effective pre-emptive analgesic.

Distinct roles for Distal-less genes Dlx3 and Dlx5 in regulating ectodermal development in Xenopus.

In vertebrates, there are six or more copies of genes related to the Drosophila pattern formation homeodomain gene Distal-less. Among this family, Dlx3 and Dlx5 share extensive sequence homology and have similar, but distinctive, expression patterns, suggesting that these two factors may have substantially redundant developmental functions. Here we show that at the earliest phases of embryogenesis in Xenopus, there are significant differences between Dlx3 and Dlx5 expression and that this correlates with different functions in the restriction of neural crest and neural plate boundaries, respectively.

Cancer chemopreventive activity of phenylpropanoid esters of sucrose, vanicoside B and lapathoside A, from Polygonum lapathifolium.

To search for cancer chemopreventive agents from natural resources, many phytochemicals have been screened using the in vitro synergistic assay indicated by the inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA). Two phenylpropanoid esters of sucrose, vanicoside B and lapathoside A, were isolated from the aerial part of Polygonum lapathifolium as inhibitors on the EBV-EA induction. These compounds also exhibited significant anti-tumor-promoting effects on mouse two-stage skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA, as an initiator) and TPA as a promoter. Further, vanicoside B exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumors initiated with an NO donor, NOR-1.

Cooperative effects of exercise training and genistein administration on bone mass in ovariectomized mice.

We reported that genistein, a soybean isoflavone, prevents bone loss caused by estrogen deficiency, without undesirable effects on the uterus. In this study, we examined cooperative effects of genistein administration and running exercise on bone mass in ovariectomized (OVX) mice. Female mice aged 7 weeks were either sham-operated or OVX and divided into six groups: (1) sham; (2) OVX; (3) OVX, treated with genistein at a submaximal dose (0.4 mg/day) subcutaneously (G); (4) OVX, exercised on a treadmill daily for 30 minutes/day at 12 m/minute on a 10 degree uphill slope (Ex); (5) OVX, given genistein and exercised (ExG); and (6) OVX, treated with 17beta-estradiol (0.03 microg/day) in the same manner as genistein (E2). Four weeks after intervention, bone mass was estimated by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Bone mineral density (BMD) of the whole femur measured by DXA was higher in both the G and the Ex groups than in the OVX group. Furthermore, BMD in the ExG group was significantly higher than that in the groups receiving either intervention alone. Bone area in distal region of the femur was significantly higher in Ex and ExG groups as compared with those in the OVX and G groups. pQCT analysis showed that the cross-sectional areas (CSAs) and periosteum perimeter at midshaft of the femur did not differ in the sham and OVX groups but were significantly higher in Ex and ExG groups. Histomorphometric analysis showed that bone formation rate/bone surface (BFR/BS) was significantly higher in both Ex and ExG groups as compared with that in non-exercised groups. The bone volume (BV/TV) in the distal femoral cancellous bone was lower in the OVX than that in the sham group, and it was restored completely in the ExG group, as in the E2 group. Thickness of the trabecular bone (Tb.Th) was higher in Ex and ExG groups than that in the OVX and G groups. These results indicate that the combined intervention of moderate exercise and the submaximal dose of genistein administration show a cooperative effect in preventing bone loss in OVX mice.

Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease.

UNLABELLED: The aim of this SPECT study was to investigate the effects of donepezil on regional cerebral blood flow (rCBF) in patients with mild to moderate Alzheimer's disease (AD) using statistical parametric mapping. METHODS: rCBF was noninvasively measured using (99m)Tc-ethyl cysteinate dimer in 35 AD patients with a Mini-Mental State Examination score > 16 on initial evaluation. Baseline and follow-up SPECT studies with a mean interval of 12 mo were performed on these patients. We used the adjusted rCBF images in the relative flow distribution (normalization of global cerebral blood flow for each patient to 50 mL/100 g/min with proportional scaling) to compare these groups through statistical parametric mapping. RESULTS: In the follow-up study, the adjusted rCBF was significantly preserved in the right and left anterior cingulate gyri, right middle temporal gyrus, right inferior parietal lobules, and prefrontal cortex of donepezil-treated AD patients, compared with placebo-treated AD patients. CONCLUSION: Treatment with donepezil for 1 y appears to reduce the decline in rCBF, suggesting preservation of functional brain activity.

New phenylpropanoid esters of sucrose from Polygonum lapathifolium.

Four new phenylpropanoid esters of sucrose, lapathosides A (1), B (2), C (3), and D (4), were isolated from the aerial parts of Polygonum lapathifolium together with known esters, vanicoside B (5) and hydropiperoside (6). The structures of 1-4 were determined by spectral (1D and 2D NMR and MS) analysis. Lapathoside A (1) and vanicoside B (2) showed significant inhibitory effects on the Epstein-Barr virus early antigen activation by tumor-promoters.

[Findings of bedside swallowing assessment and brain computerized tomography in patients with chronic cerebral infarction, and their outcome].

To estimate the usefulness of the bedside swallowing assessment proposed by Smithard et al and neuroimaging findings characteristic for dysphagia, we studied the outcome of 102 patients with chronic cerebral infarction after assessment of swallowing by this test with brain computerized tomography (CT). All patients had a variety of motor disturbance and were admitted on a long-term medicare basis. They were divided into two groups according to the findings: the positive group (n = 33), who showed any of the listed types of difficulty in swallowing water, and the negative group (n = 69). Followed up to 2.2 years, their outcomes were studied. CT findings were studied on type of infarction, number and laterality of infarction, grade of periventricular lucency (PVL), presence of ventricular dilatation (VD), and severity of cortical atrophy (CA). The mean age was 76.4 years at registration and 61 were men. The frequency of severe dementia and disturbed ADL were significantly higher in the positive group. Eighteen patients died during the observation period and 15 of those were in the positive group, indicating higher annual death rate (29.9% vs 2.2% in the negative group). All of the 15 patients in the positive group died of pneumonia. CT findings showed high incidence of multiple infarction, bilateral hemispheric lesion, severe PVL, VD, and severe CA in the positive group. These findings indicated that this evaluation method was useful in screening swallow function for patients with cerebral infarction in the chronic phase. Furthermore, CT findings suggested that severe white matter lesion, VD, and severe CA as well as multiple infarction seen in bilateral hemisphere was related to dysphagia, probably due to multiple factors involving pyramidal- and extrapyramidal-tracts with higher brain function.

Orexin depolarizes rat hypothalamic paraventricular nucleus neurons.

Orexins, also called hypocretins, are newly discovered hypothalamic peptides that are thought to be involved in various physiological functions. In spite of the fact that orexin receptors, especially orexin receptor 2, are abundant in the hypothalamic paraventricular nucleus (PVN), the effects of orexins on PVN neurons remain unknown. Using a whole cell patch-clamp recording technique, we investigated the effects of orexin-B on PVN neurons of rat brain slices. Bath application of orexin-B (0.01-1.0 microM) depolarized 80.8% of type 1 (n = 26) and 79.2% of type 2 neurons tested (n = 24) in the PVN in a concentration-dependent manner. The effects of orexin-B persisted in the presence of TTX (1 microM), indicating that these depolarizing effects were generated postsynaptically. Addition of Cd(2+) (1 mM) to artificial cerebrospinal fluid containing TTX (1 microM) significantly reduced the depolarizing effect in type 2 neurons. These results suggest that orexin-B has excitatory effects on the PVN neurons mediated via a depolarization of the membrane potential.

MK-801 reduces non-noxious stimulus-evoked Fos-like immunoreactivity in the spinal cord of rats with chronic constriction nerve injury.

We investigated the role of N-methyl-D-aspartate (NMDA) receptors on non-noxious stimulus-induced pain by examining the effect of MK-801, a non-competitive NMDA receptor antagonist, on Fos-like immunoreactivity (FLI) in the spinal dorsal horn by non-noxious stimulation to rats with chronic constriction injury (CCI) of the sciatic nerve. In CCI rats that did not receive the non-noxious stimulus, FLI was significantly increased in laminae V/VI of the dorsal horn at the 7th and 14th days after surgery relative to sham rats. When CCI rats received non-noxious stimuli, rubbing the plantar of the hind paw, FLI in laminae I/II at the 14th day was significantly increased relative to CCI rats that did not receive the stimulation. In sham rats, the same stimulus significantly decreased FLI in laminae III/IV and V/VI at the 7th and 14th day. When MK-801 was administered intraperitoneally prior to non-noxious stimulation in CCI rats at the 14th day after surgery, the stimulus-induced FLI in laminae I/II in CCI rats was significantly reduced. This study indicates that NMDA receptor is involved in upregulating FLI in response to non-noxious stimulation of CCI rats.

Magnetization transfer measurements of the hippocampus in the early diagnosis of Alzheimer's disease.

We measured magnetization transfer ratios (MTRs) of the hippocampus in 38 patients with Alzheimer's disease (AD), including very mild (Clinical Dementia Rating [CDR] 0.5, n=12), mild (CDR 1, n=14), and moderate stages (CDR 2, n=12), and in 21 healthy elderly control subjects. Medial temporal lobe atrophy was graded subjectively on a five-point scale by two observers blinded to clinical data. Compared with the controls, each of the AD groups, including the very mild group, had significant atrophy of the medial temporal lobe and a decrease in MTRs of the hippocampus. Logistic regression analysis revealed that the overall discrimination rate with MTR measurement and visual analysis of the atrophy was 85% and 73% between the control group and the CDR 0.5 group, 89% and 80% between the control group and the CDR 1 group, and 100% and 91% between the control group and the CDR 2 group, respectively. MTR measurements may provide additional information in detecting structural damage of the hippocampus of AD and be helpful in providing improved diagnosis and early detection of AD.

Magnetisation transfer measurements of the subcortical grey and white matter in Parkinson's disease with and without dementia and in progressive supranuclear palsy.

We measured the magnetisation transfer ratio (MTR) in the subcortical grey and white matter of 11 patients with idiopathic Parkinson's disease (PD) without dementia, six with PD with dementia (PDD), six with progressive supranuclear palsy (PSP), and 12 elderly control subjects to assess regional differences in structural brain damage. There were no significant differences in MTR in any region between PD and controls. However, patients with PDD had significantly lower MTR in the subcortical white matter, including the frontal white matter and the genu of the corpus callosum than the controls, whereas PSP had significantly lower MTR in the subcortical grey matter, including the putamen, globus pallidus and thalamus, in addition to the subcortical white matter. This suggests that regional patterns of structural brain damage can be detected using the magnetisation transfer technique. Measurement of MTR in the subcortical grey and white matter may be useful in differential diagnosis.

[Present status and problems in medical care for demented patients using public counselling facilities].

To clarify the present status and problems in medical care for the elderly with dementia, 103 cases were studied according to the descriptive records obtained at a public counselling facility for dementia, based on interviews with patients' families. Their records were analysed based on their background, severity of dementia (clinical dementia rating: CDR), and counselling content. There were 75 demented patients with a CDR score of 1 or more, and 50 of them were women aged 54 to 90, while the remaining 25 men were aged 55 to 88. The consultation content was clustered into 5 codes: code 1, evaluation of dementia and/or dementia-related symptoms including psychiatric symptoms and behavioral disturbance; code 2, methods to manage patients; code 3, methods to take a patient to a medical institution; code 4, questions regarding medical treatment and drugs prescribed at present; code 5, information on the welfare resources provided. In most of the 75 patients, the degree of dementia deteriorated insidiously without any physical symptoms. The key person and/or caregiver was usually an elderly spouse, and the family noticed dementia only after cognitive impairment progressed with or without troublesome symptoms. Hallucination was a common troublesome symptom. Concerning consultation content, codes 1, 2, and 3 were common, while 13 cases had dissatisfaction with their medical treatment. Therefore, it was necessary to explain the significance of early diagnosis of dementia to families and their caregivers. There were also many families who felt strain and wondered about what hospital or department to take the patient to. In addition, it seemed that explanation on the clinical course and adverse drug reactions, advice for the correspondence with psychiatric symptoms and abnormal behaviour, and information services concerning utilization of social resources was not yet sufficient.