Development of an assessment sheet for fall prediction in stroke inpatients in convalescent rehabilitation wards in Japan

Objective We conducted a study to develop an assessment sheet for fall prediction in stroke inpatients that is handy and reliable to help ward staff to devise a fall prevention strategy for each inpatient immediately upon admission. Methods The study consisted of three steps: (1) developing a data sampling form to record variables related to risk of falls in stroke inpatients and conducting a follow-up survey for stroke inpatients from their admission to discharge by using the form; (2) carrying out analyses of characteristics of the present subjects and selecting variables showing a high hazard ratio (HR) for falls using the Cox regression analysis; (3) developing an assessment sheet for fall prediction involving variables giving the integral coefficient for each variable in accordance with the HR determined in the second step. Results and discussion (1) Subjects of the present survey were 704 inpatients from 17 hospitals including 270 fallers. (2) We selected seven variables as predictors of the first fall: central paralysis, history of previous falls, use of psychotropic medicines, visual impairment, urinary incontinence, mode of locomotion and cognitive impairment. (3) We made 960 trial models in combination with possible coefficients for each variable, and among them we finally selected the most suitable model giving coefficient number 1 to each variable except mode of locomotion, which was given 1 or 2. The area under the ROC curve of the selected model was 0.73, and sensitivity and specificity were 0.70 and 0.69, respectively (4/5 at the cut-off point). Scores calculated from the assessment sheets of the present subjects by adding coefficients of each variable showed normal distribution and a significantly higher mean score in fallers (4.94 ± 1.29) than in non-fallers (3.65 ± 1.58) (P = 0.001). The value of the Barthel Index as the index of ADL of each subject was indicated to be in proportion to the assessment score of each subject. Conclusion We developed an assessment sheet for fall prediction in stroke inpatients that was shown to be available and valid to screen inpatients with risk of falls immediately upon admission.     

A selective plasmin inhibitor, trans-aminomethylcyclohexanecarbonyl-L-(O-picolyl)tyrosine-octylamide (YO-2), induces thymocyte apoptosis

The treatment of rat thymocytes with YO-2, a novel inhibitor of plasmin, resulted in an increase in DNA fragmentation. DNA fragmentation was also induced by another YO compounds such as YO-0, -3, -4 and -5. These YO compounds are the inhibitor of plasmin activity. On the other hand, YO-1, -6 and -8 that hardly inhibit plasmin activity had no effect on DNA fragmentation. Analysis of fragmented DNA from thymocytes treated with YO-2 by agarose gel electrophoresis revealed that the compound caused internucleosomal DNA fragmentation. In addition, judging from a laser scanning microscopy, annexin V-positive and propidium iodide-negative cells were increased by the treatment of the cells with the compound. Moreover, chromatin condensation was observed in thymocytes treated with the compound. These results demonstrated that YO-2 induces thymocyte apoptosis. There seemed to be some correlation between the apoptosis induced by YO compounds and their plasmin inhibitory effect. However, because the other protease inhibitors including pepstatin A, leupeptin, AEBSF, DFP and E-64-d did not affect DNA fragmentation, YO compounds are likely to have unique mechanism on plasmin or to show the effect on the other plasmin-like proteases. The plasmin inhibitory activity may have an important role in YO-2-induced apoptosis. Furthermore, the stimulations of caspase-8, -9 and -3-like activities were observed in thymocytes treated with YO-2. These results suggest that YO-2 induces thymocyte apoptosis via activation of caspase cascade.     

Leukotriene C4 synthase gene A(-444)C polymorphism and clinical response to a CYS-LT(1) antagonist,pranlukast, in Japanese patients with moderate asthma

CysLT(1) antagonists are effective for a subset of patients with asthma; however, there has been no good way to predict a given patient's response. We examined the interaction between the clinical response to a cysLT(1) antagonist, pranlukast, and DNA sequence variant A(-444)C in leukotriene C(4) synthase (LTC(4) S) gene in Japanese patients with moderate asthma. The frequency of LTC(4) S C(-444) allele was 21.6% in the Japanese general population (n = 171) and 19.4% in the asthmatic subjects ( n= 349). A 4-week prospective, open trial of pranlukast (225 mg twice daily) was performed in 50 patients with moderate asthma who had been well controlled with inhaled corticosteroid (beclomethasone 400-800 microg/day or fluticasone 200-400 microg/day). The C(-444) allele carriers (n = 16) responded better to pranlukast compared to the A(-444) allele homozygotes ( n= 31) [14.3 5.3% vs. 3.1 2.4% improvement of forced expiratory volume in one second (FEV(1) ), 0.01], while LTC(4) S genotype-stratified response to inhaled beta-agonist salbutamol (200 microg) was not observed (17.5 2.1% vs. 18.7 2.2% improvement of FEV(1) ). Univariate analysis demonstrated that the better response to pranlukast (more than 10% improvement of FEV(1) ) was correlated with LTC(4) S genotype (P < 0.01) and pretreatment airway reversibility to salbutamol (P < 0.01), but not with sex, age, atopic status, urinary leukotriene E(4) excretion rate, or daily dose of inhaled corticosteroid. Furthermore, multivariate regression analysis suggested that LTC(4) S genotype and the bronchodilatory effect of salbutamol were independent variables to predict the clinical response to pranlukast (P < 0.05). We conclude that LTC(4) S genotype is predictive of the clinical response to a cysLT(1) antagonist, pranlukast, in Japanese patients with moderate asthma.     

Heat stability of the lyophilized Sabin poliovaccine

In this study we lyophilized three types of live attenuated polioviruses (Sabin vaccine strains) and evaluated the lyophilized vaccine viruses' heat stability. The virus titers were measured after heating at 37 and 45 and then compared with the titers of conventional liquid vaccine viruses similarly treated. The results showed that lyophilization, while slightly reducing vaccine virus titers, had a far greater sparing effect on subsequent heat inactivation of lyophilized vaccine viruses, thus demonstrating its validity for the improvement of the vaccine.     

Falling asleep while driving and automobile accidents among patients with obstructive sleep apnea-hypopnea syndrome

Among 448 patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), 40 patients (8.9%) had been involved in one or more automobile accidents during the preceding 5 years. The main cause of these accidents was falling asleep while driving. Excessive sleepiness during driving was associated with an Epworth sleepiness scale (ESS) score of > 11 and/or an apnea-hypopnea index (AHI) of > 15. The automobile accident rate among 182 patients with severe OSAHS (AHI > 30) was significantly higher than the rate among 106 simple snorers (AHI < 5). Although four of the simple snorers were involved in automobile accidents, their ESS scores were all very high (15 or more).     

New bone-seeking agent: Animal study of Tc-99m-incadronate

OBJECTIVE: Disodium cycloheptylaminomethylenediphosphonate monohydrate (incadronate disodium) is a third-generation bisphosphonate compound which potently inhibits bone resorption, and a highly effective drug in the treatment of metastatic bone disease. We first labeled incadronate disodium with 99mTc, and examined its biodistribution and bone uptake after intravenous injection in rats to assess its potential for clinical use as a bone-seeking agent for judgment of the therapeutic effect of incadronate on bone metastases. Bone scan with 99mTc-labeled incadronate (99mTc-incadronate) may yield important information prior to the use of incadronate for treatment of bone metastases. METHODS: Synthesis of 99mTc-incadronate was carried out by reduction of 99mTc-pertechnetate in the presence of SnCl2 and N2 gas. Normal rats were injected with 18.5 MBq (0.5 mCi) 99mTc-incadronate in a volume of 0.1 ml intravenously and then sacrificed at 15 min, 30 min, 1 h or 2 h (six rats at each time point) after injection. Samples of muscle, stomach, small intestine, kidney, liver and bone (femur) were taken and weighed. In addition, a 1-ml sample of blood was drawn from the heart, and urine was taken from the urinary bladder immediately after sacrifice. Samples were measured for radioactivity and expressed as percent uptake of injected dose per gram or per milliliter (% ID/g or ml). Bone-to-blood and bone-to-muscle uptake ratios were determined from the % ID/g or ml values for these organs. RESULTS: The greatest accumulation of 99mTc-incadronate was found in bone. Radioactivity in bone was as high as 3.22 +/- 0.68% ID/g at 2 hours after injection. Scintigraphic images of 99mTc-incadronate in normal rats revealed highly selective skeletal uptake. CONCLUSION: 99mTc-incadronate exhibited high uptake in bone, and relatively low uptake in soft tissue, suggesting that it may be useful as a bone-seeking agent for judgment of the therapeutic effect of incadronate on bone metastases, by determining the degree of its accumulation in metastatic bone lesions.     

CyberKnife stereotactic irradiation for metastatic brain tumors

BACKGROUND: The CyberKnife provides a new technique for performing frameless stereotactic irradiation. So far, few reports have been published on clinical outcomes obtained with the CyberKnife. This report summarizes our clinical experience with CyberKnife irradiation for metastatic brain tumors. MATERIALS AND METHODS: Seventy-seven lesions (48 patients) were evaluated and analyzed, and 66 lesions in 41 patients were treated with stereotactic radiosurgery (SRS). The prescribed dose was 9 to 30 Gy. RESULTS: Freedom from progression of the tumors was more likely with a prescribed dose of at least 24 Gy than with one of less than 20 Gy (p=0.0244; log-rank test). The CR (complete response) rate was significantly higher when D99 was at least 24 Gy (p=0.0045). There were no severe side effects. CONCLUSION: Stereotactic irradiation with the CyberKnife for metastatic brain tumors is effective and safe. D99 should be at least 24 Gy for CyberKnife SRS treatment.     

Monte Carlo calculation of depth doses for small field of CyberKnife

PURPOSE: A Monte Carlo (MC) model of CyberKnife was developed as a quality assurance tool. The percentage depth dose (%dd) was verified by using this model. MATERIALS AND METHODS: An MC model was developed with Electron Gamma Shower version 4 (EGS4) in two steps: (1) a model of the CyberKnife treatment head and (2) a model of the collimator and phantom. The bremsstrahlung spectrum was calculated using the first model, and this spectrum was then used to calculate %dds with the second model. The calculated %dds for a large field (60 mm diameter) and three small fields (30, 15, and 5 mm diameter) were compared with those measured with a diamond detector. RESULTS AND DISCUSSION: The MC-calculated and measured %dd-curves for the 60 mm diameter field were in excellent agreement (<1.85%), thus confirming the validity of the model. Discrepancies between the calculated and measured %dd-curves increased with decreasing field size, with considerable discrepancy (11.62%) for the 5 mm diameter field due to lateral electron disequilibrium. Accurate dose can be determined with MC even in small fields. CONCLUSION: The MC technique can provide reliable standard data for accurate dose delivery with high-technology radiotherapies using small beams.     

High dose rate endovascular brachytherapy in aorto-iliac lesion for the prevention of restenosis

This study examined the applicability of endovascular brachytherapy to larger del arteries such as the abdominal aorta and iliac artery. Endovascular brachytherapy using an Ir-192 HDR source was administered 11 times to nine patients who had undergone percutaneous transluminal angioplasty (PTA) between 1995 and 1999. The follow-up lasted 13 to 55 months after treatment (median, 24 months). Eight of the 11 lesions have been controlled so far. Although one case developed thrombus inside the stent five months later, recanalization was achieved by means of retreatment. One patient who underwent low-dose irradiation (6 Gy) without stent implantation showed restenosis five months after treatment. We used a centering catheter that did not block the blood stream for exact centering of the radiation source in larger vessels such as the abdominal aorta. Although endovascular brachytherapy is a promising and safe procedure, careful follow-up is needed to detect untoward reactions such as thrombosis.