Self-assessment of Rheumatoid Arthritis Disease Activity Using a Smartphone Application. Development and 3-month Feasibility Study.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Methodologies, Models and Algorithms for Patients Rehabilitation". BACKGROUND: Rheumatoid arthritis (RA) is a progressive inflammatory disease that causes damage to multiple joints, decline in functional status, and premature mortality. Thus, effective and frequent objective assessments are necessary. Then, we developed a self-assessment system for RA patients based on a smartphone application. OBJECTIVE: The purpose of this study was to investigate the feasibility of a self-assessment system for RA patients using a smartphone application. METHODS: We measured daily disease activity in nine RA patients who used the smartphone application for a period of three months. A disease activity score (DAS28) predictive model was used and feedback comments relating to disease activity were shown to patients via the smartphone application each day. To assess participants' RA disease activity, the DAS28 based on the C-reactive protein level was measured by a rheumatologist during monthly clinical visits. RESULTS: The disease activity measured by the application correlated well with the patients' actual disease activity during the 3-month period, as assessed by clinical examination. Furthermore, most participants gave favourable responses to a questionnaire administered at the end of the 3-month period containing questions relating to the ease of use and usefulness of the system. CONCLUSIONS: The results of this feasibility study indicated that the DAS28 predictive model can longitudinally predict DAS28 and may be an acceptable and useful tool for assessment of RA disease activity for both patients and healthcare providers.

Assessment of hemorrhage in pituitary macroadenoma by T2*-weighted gradient-echo MR imaging.

BACKGROUND AND PURPOSE: Intratumoral hemorrhage occurs frequently in pituitary macroadenoma and manifests as pituitary apoplexy and recent or old silent hemorrhage. T2*-weighted gradient-echo (GE) MR imaging is the most sensitive sequence for the detection of acute and old intracranial hemorrhage. T2*-weighted GE MR imaging was used to investigate intratumoral hemorrhage in pituitary macroadenomas. MATERIALS AND METHODS: Twenty-five consecutive patients who underwent total or subtotal resection of pituitary macroadenoma with heights from 17 to 53 mm, including 1 patient with classic pituitary apoplexy, underwent MR imaging before surgery, including T2*-weighted GE MR imaging. For histologic assessment of the hemorrhage in whole surgical specimens, we used hematoxylin-eosin staining. RESULTS: T2*-weighted GE MR imaging detected various types of dark lesions, such as "rim," "mass," "spot," and "diffuse" and combinations, indicating clinical and subclinical intratumoral hemorrhage in 12 of the 25 patients. The presence of intratumoral dark lesions on T2*-weighted GE MR imaging correlated significantly with the hemorrhagic findings on T1- and T2-weighted MR imaging (P < .02 and <.01, respectively), and the surgical and histologic hemorrhagic findings (P < .001 and <.001, respectively). CONCLUSION: T2*-weighted GE MR imaging could detect intratumoral hemorrhage in pituitary adenomas as various dark appearances. Therefore, this technique might be useful for the assessment of recent and old intratumoral hemorrhagic events in patients with pituitary macroadenomas.

Energetic costs of bipedal and quadrupedal walking in Japanese macaques.

We investigated the energetic costs of quadrupedal and bipedal walking in two Japanese macaques. The subjects were engaged in traditional bipedal performance for years, and are extremely adept bipeds. The experiment was conducted in an airtight chamber with a gas analyzer. The subjects walked quadrupedally and bipedally at fixed velocities (<5 km/hr) on a treadmill in the chamber for 2.5-6 min. We estimated energy consumption from carbon dioxide (CO2) production. While walking bipedally, energetic expenditure increased by 30% relative to quadrupedalism in one subject, and by 20% in another younger subject. Energetic costs increased linearly with velocity in quadrupedalism and bipedalism, with bipedal/quadrupedal ratios remaining almost constant. Our experiments were relatively short in duration, and thus the observed locomotor costs may include presteady-state high values. However, there was no difference in experimental duration between bipedal and quadrupedal trials. Thus, the issue of steady state cannot cancel the difference in energetic costs. Furthermore, we observed that switching of locomotor mode (quadrupedalism to bipedalism) during a session resulted in a significant increase of CO2 production. Taylor and Rowntree ([1973] Science 179:186-187) noted that the energetic costs for bipedal and quadrupedal walking were the same in chimpanzees and capuchin monkeys. Although the reason for this inconsistency is not clear, species-specific differences should be considered regarding bipedal locomotor energetics among nonhuman primates. Extra costs for bipedalism may not be great in these macaques. Indeed, it is known that suspensory locomotion in Ateles consumes 1.3-1.4 times as much energy relative to quadrupedal progression. This excess ratio surpasses the bipedal/quadrupedal energetic ratios in these macaques.

[Risk assessment in urgent or emergent coronary artery bypass grafting for acute coronary syndrome].

Emergent coronary artery bypass grafting (CABG) for the treatment of acute coronary syndrome has increased the operative mortality. Forty-nine patients underwent urgent or emergent CABG for the treatment of medically refractory unstable angina in 10 patients, and for acute myocardial infarction (AMI) in 39 patients. Ten operative deaths were occurred in the AMI patients, and the mortality was 20 percent. The preoperative risk factors were evaluated in 10 patients who died in the operative period. Cardiopulmonary resuscitation before operation, intra aortic balloon pumping, the use of catecholamine, and intubation with or without percutaneous cardiopulmonary support revealed operative risk factor. Because the patients who have preoperatively shock, it seemed to be needed that the rescue of the patients should improve the clinical results for urgent or emergent CABG.

[Assessment of ECG-gated myocardial SPECT analysis program with cardiac phantom and clinical data].

PURPOSES: ECG-gated myocardial SPECT program (QGS) is coming into wide use. This program permits measurement of end-diastolic volume (EDV), and end-systolic volume (ESV) and ejection fraction (EF) by automatic detection of myocardial edges. We assessed the reproducibility, accuracy, factors that affect the measurement of these indices using a cardiac phantom and clinical data. METHODS: In the phantom study, we evaluated the effects of ventricular volume, location, absorption, acquisition time, enlarged acquisition and pre-filter on the calculated indices. In the clinical study using 99mTc-MIBI, reproducibility between 2 observers, comparison with left ventriculography and effects of pre-filter were assessed. In clinical cases of 201TI and 123I-BMIPP, left ventricular volume and EF were also analyzed by QGS with various pre-filters. RESULTS: Although the true phantom volumes (y) and calculated volumes (x) showed an excellent linear correlation (y = 0.94x - 13.8, r = 0.999), calculated volumes were significantly under-estimated by 14.5-33.8%. An absorbent material around the phantom caused reduction in calculated volumes by 4.1-9.1%. Duration of acquisition times, 3 to 60 seconds per projection, did not influence the calculation of the parameters. With enlarged data collection, calculated volume (37 ml) was larger than that of normal acquisition (33 ml). When the cut-off frequency of Butterworth filter was changed, these indices of volume and EF were almost stable over 0.41 cycle/cm. There was an excellent correlation in intra-observer measurements for EDV (r = 0.998, p < 0.0001), ESV (r = 0.998, p < 0.0001) and EF (r = 0.995, p < 0.0001). In comparison with left ventriculography, correlation of parameters was good in ESV (r = 0.91, p < 0.0001), EF (r = 0.88, p < 0.0001), but was fair in EDV (r = 0.78, p < 0.0001). The QGS program underestimated EDV, ESV and EF. CONCLUSION: QGS program with gated SPECT is useful to calculate relative volume and EF. However, to calculate absolute values, we should understand the various factors that affect the result of QGS.

Association of autoimmune thyroid disease with a microsatellite marker for the thyrotropin receptor gene and CTLA-4 in a Japanese population.

To examine the genetic contribution of the thyroid-stimulating hormone receptor (TSHR, or thyrotropin receptor) gene to autoimmune thyroid disease (AITD), we identified a dinucleotide repeat polymorphism near the TSHR gene that mapped to an 8.6 cM interval between D14S74 and D14S55 on the long arm of human chromosome 14. Association studies revealed a significant difference (p = 3.8 x 10(-5) between the TSHR microsatellite allele frequency distribution in 81 unrelated Japanese AITD patients and 113 Japanese controls, with a significant increase in the 180 pb allele (allele 1) of the microsatellite sequence (p = 5.8 x 10(-7). The risk for AITD with the 180 bp allele was 3.5, with association highly significant in female patients (p = 1.1 x 10(-5) and less dramatic, but still significant, in male patients (p = .02). These results suggest that the 180 bp allele of the TSHR microsatellite is associated with a susceptibility locus for AITD in Japanese patients. Two additional genetic markers have been evaluated for association in the Japanese AITD patients. The TSHR codon 52 (C52-->A52) transition mutation was not observed in the Japanese. A polymorphism for the CTLA-4 gene was genotyped and, while association with AITD was not observed (p = .15), a significant association was observed between CTLA-4 alleles of 110 bp (p = .01) and 106 bp (p = .004) and susceptibility to primary hypothyroidism or idiopathic myxedema, respectively.

[Anomalous origin of the left coronary artery from the pulmonary trunk with myocardial infarction and severe left ventricular dysfunction in infancy--assessment of myocardial damage using SPECT studies with 201TlCl and 123I-BMIPP].

A 4-month-old male infant with Bland-White-Garland (BWG) syndrome complicated myocardial infarction was reported. Signs included tachypnea, coughing, and failure to thrive. However, there was no sign of myocardial infarction. A chest radiograph revealed cardiomegaly (CTR = 65%) and electrocardiogram showed abnormal Q waves in I, aVL, V6 leads. Cardiac catheterization and angiography revealed marked dilatation of left ventricle (end-diastolic volume = 384 ml/m2) and extremely depressed ejection fraction (16%), confirming the diagnosis of BWG syndrome. A 201TlCl-myocardial SPECT demonstrated apical defect and hypoperfusion in the anterolateral, inferoposterior walls, whereas 123I-beta-methyl-p-iodophenylpentadecanoic-acid (123I-BMIPP) SPECT showed a wider defect area. SPECT studies with 201TlCl and 123I-BMIPP, are useful to assess myocardial viability more accurately in BWG syndrome.

In vitro assessment for neurotoxicity of antitumor agents before local administration into central nervous system.

In vitro assays for neurotoxicity with the aid of cultured mouse fetal neurons and glial cells were applied to investigate neurotoxicity of recombinant murine interferon-beta (rMuIFN-beta). These data were compared with those for MTX, ADR, and ACNU. The range of concentrations of the drugs used in these experiments spanned their clinically achievable concentrations in patient serum (IFN-beta: 1 x 10(4) IU/ml, MTX: 100 micrograms/ml, ADR: 20 micrograms/ml, ACNU: 20 micrograms/ml). rMuIFN- beta damaged both neurons and glial cells at concentrations of more than 1 x 10(5) IU/ml but did not damage them at 1 x 10(4) IU/ml or less. Microtubule-associated protein 1A (MAP1A) staining was decreased in rMuIFN-beta-treated (more than 1 x 10(5) IU/ml) neutrons. In conclusion, since IFN-beta may have some neurotoxic effects at concentrations higher than 1 x 10(5) IU/ml, it should be administered carefully, as should other antitumor agents, into the tumor cavity in the CNS following surgery.

[Diagnosis and prognosis of elderly patients with coronary artery disease: assessment with dipyridamole thallium imaging].

Noninvasive evaluation of coronary artery disease is difficult in elderly patients because of their limited exercise-capacity. The diagnostic and prognostic value of dipyridamole perfusion scintigraphy was assessed in 147 patients aged 65 years and older. All patients underwent coronary angiography. Initially, 32 patients had percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). The other 115 patients were first treated medically and followed for a mean of 29 +/- 22 months. Nine patients (7.9%) had cardiac events including cardiac death and coronary intervention (PTCA or CABG) during the follow-up. Dipyridamole perfusion scintigraphy was performed safely in all patients, whereas treadmill exercise testing could not be adequately performed in 24 patients, 18 of whom had multivessel disease. Multiple regression analysis showed that: fixed defect and reversible defect were powerful detectors of coronary lesions (p = 0.0001, p = 0.0027, respectively), all patients with fixed disease and 94% of patients with only reversible defect had significant coronary lesion; Diffuse slow washout and ST depression were statistically significant for detecting multivessel coronary lesions in patients with fixed disease (p = 0.0001, p = 0.017, respectively), the sensitivity and specificity of diffuse slow washout and/or ST depression for detecting multivessel coronary lesions ware 85% and 74%, respectively, and ST depression was statistically significant for detecting multivessel coronary lesions (p = 0.0002) in patients with only reversible defect, the sensitivity and specificity of ST depression were 88% and 64%, respectively. Cox survival analysis identified diffuse slow washout as the best predictor of future cardiac events among the scintigraphic variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Vertebral measurements for assessment of osteoporosis.

We measured the vertebral heights and spinal bone mineral density (BMD) of healthy women, and morphometrically evaluated the physiological features of the vertebrae to investigate the relationship of BMD to types of spinal deformity as well as the radiographic detection rate for decreased vertebral bone density. Vertebral BMD was measured from L1 to L4 using dual X-ray absorptiometry and from L1 to L3 using quantitative computed tomography in 245 healthy women ranging in age from 22 to 81 years. The vertebral heights, anterior (Ha), middle (Hm), and posterior (Hp), were measured from T12 through L5, and the Ha/Hp and Hm/Hp ratios were calculated. Although the age-related reduction of vertebral height was not as marked as that of BMD, the vertebral heights, especially the Ha and Hm from T12 to L5 vertebrae, and the Ha/Hp and Hm/Hp from T12 to L3, significantly decreased with age. The presence of a wedge-shaped deformity was strongly related to cortical BMD, and biconcave deformity to trabecular BMD. Although investigation of the sensitivity and specificity of several criteria revealed that vertebra-specific dimension criteria are useful in the detection of decreased bone density, the detection of decreased BMD using vertebral measurements is considered to be limited.

[Clinical usefulness of visual analog scale for assessment of dyspnea at rest in patients with chronic respiratory diseases].

To evaluate the validity and clinical usefulness of the visual analog scale (VAS) for the measurement of dyspnea at rest, we employed the 150 mm VAS in 29 chronic respiratory disease patients who were clinically stable, and repeated the measurement 4 weeks and 8 weeks later for the evaluation of reproducibility. For the 8-week period, the individual medical treatments remained generally unchanged in all patients. Two patients were excluded from the study due to infection and pneumothorax. Dyspnea at rest was detected on VAS in 23 patients at the first measurement. The VAS measurement was 23.9 +/- 28.4 (mean +/- SD) mm at the first time, 22.0 +/- 23.1 mm at the 4th week, and 22.4 +/- 26.0 mm at the 8th week. There was no significant change among the three measurements. Twenty among the 23 patients with VAS indicative of dyspnea at rest were categorized into grades 4 and 5 of the Fletcher dyspnea category. However, the intensity of dyspnea was distributed widely within each Fletcher category. These results lead to the conclusion that VAS shows good reproducibility over a period of as long as 8 weeks and that VAS measurements can reveal patient-to-patient individual differences in dyspnea intensity which cannot be detected by the Fletcher dyspnea category. We propose that measuring dyspnea at rest using VAS is a useful method to obtain a valid clinical parameter.

Mental health in family members living with elders.

We assessed the mental health conditions of 217 subjects who took care of elders at home, using our depression scale by the surveillance of the elders living at home in Ibaraki Prefecture. An analysis was made on how depression in the caretakers was related with each item of demographical results of the caretakers and the elders living together at home, and with ADL, depression, dementia, personality change and the personality trait of the elders. Our study revealed that depression, personality change and the viscous character of the elders are three factors associated with depression in the female caretakers. Furthermore, we pointed out the necessity of an education campaign to provide the caretakers with information on the elders' personality and personality change for maintenance of the good mental health of the caretakers living with the elders.

Calcaneus as a site for assessment of bone mineral density: evaluation in cadavers and healthy volunteers.

OBJECTIVE: The value of calcaneal dual-energy X-ray absorptiometry for monitoring changes in bone mineral density has not yet been established. Accordingly, the focus of this study was to determine the usefulness of the calcaneus as the site for bone mineral density measurement with dual-energy X-ray absorptiometry. SUBJECTS AND METHODS: Dual-energy X-ray absorptiometry of the calcaneus was performed in 19 specimens derived from 11 cadavers and 337 healthy volunteers to assess accuracy, in vivo precision, and age-related changes in bone mineral density. We also compared calcaneal bone mineral density determined by dual-energy X-ray absorptiometry with lumbar spine bone mineral density determined by dual-energy X-ray absorptiometry (L1-L4) or quantitative CT (L3). RESULTS: Studies of specimens showed that dual-energy X-ray absorptiometry had an error rate of 6%. In addition, strong correlations were found between bone mineral content and ash weight (r = .97, p < .0001) and between bone mineral density and ash density (r = .87, p < .0001). In vivo studies showed moderate correlations between calcaneal bone mineral density determined by dual-energy X-ray absorptiometry and lumbar spine bone mineral density determined by dual-energy X-ray absorptiometry (men, r = .77, p < .0001; women, r = .76, p < .0001) and lumbar spine bone mineral density by quantitative CT (men, r = .68, p < .0001; women, r = .68, p < .0001). Calcaneal bone mineral density measured by dual-energy X-ray absorptiometry and lumbar spine bone mineral density measured by quantitative CT continued to decrease throughout the postmenopausal period. However, lumbar spine bone mineral density determined by dual-energy X-ray absorptiometry did not show further decreases in subjects more than 70 years old. CONCLUSION: Taken together, these results suggest that the calcaneus can be used as an additional site for determining bone mineral density to assess osteopenia in patients when deformities of the spine make quantitative CT or other methods of density measurement impossible.

[Assessment of prognosis of old myocardial infarction].

In an attempt to predict high risk myocardial infarction, we studied 201 patients with Q wave infarction with dipyridamole-loading thallium-201 myocardial perfusion scintigraphy (D-MPS), left ventriculography, coronary angiography and treadmill exercise testing. The results of these tests were related to the use of initial PTCA or CABG, and the occurrence of cardiac deaths and nonfatal cardiac events during a mean follow-up period of 39 months. Three high risk parameters were identified by D-MPS; partial redistribution, diffuse slow washout, and extensive fixed defects. The patients were categorized into 3 groups according to the numbers of high risk parameters: group A (n = 50), patients with 2 or more high risk parameters; group B (n = 95), patients with one high risk parameter; group C (n = 56), patients without a high risk parameter. The prevalence of 3-, 2-, and one- or insignificant vessel disease was 72, 20 and 8% in group A, 15, 16, and 69% in group B, and 5, 13 and 82% in group C, respectively. Initial PTCA or CABG was performed in 42% of the patients in group A, 5% of the patients in group B, and 2% of the patients in group C. Among medically-treated patients, cardiac deaths occurred in 31% in group A, 4% in group B, and in none in group C. Nonfatal cardiac events occurred in 24, 12, and 4%, respectively. Coronary angiography revealed 3-vessel disease in 53 patients, 2-vessel disease in 32, and one-vessel disease or insignificant lesions in 116 patients. Initial PTCA or CABG was performed in 45% of the patients with 3-vessel disease, 6% of those with 2-vessel disease and 1% of those with one-vessel disease. Among medically-treated patients, cardiac deaths occurred in 31% with 3-vessel disease, 7% with 2-vessel disease, and in 2% with one-vessel disease. Nonfatal cardiac events occurred in 17, 10, and 3%, respectively.

[Assessment of 99mTc-DMSA renography and uptake compared with creatinine clearance in rats with drug-induced nephrotoxicity--II. Cisplatin-induced nephrotoxicity].

For evaluation of technetium-99m dimercaptosuccinic acid (99mTc-DMSA) renal uptake as an absolute renal function, 99mTc-DMSA uptake was compared with endogenous creatinine clearance (Ccr) in cisplatin-induced nephrotoxicity. At first, Male Wistar rats were given intraperitoneally 1.8 mg/kg/day of cisplatin for periods of 3, 5, 7 and 9 days. On the next day, 99mTc-DMSA uptake and Ccr were measured. Ccr of 5-day treated group was significantly lower than that of control (0.13 +/- 0.10 vs 0.34 +/- 0.05 ml/min/100 g; p less than 0.01) but 99mTc-DMSA uptake did not change. 99mTc-DMSA uptake of 7-day treated group was significantly lower than that of control (28.57 +/- 7.23 vs 39.84 +/- 2.23%; p less than 0.01). As the second experiment, cisplatin (3.6 mg/kg/day) was given intraperitoneally on the 1st, 2nd, 15th and 16th day. On the 5th, 8th, 11th, 15th, 20th, 23rd, 26th and 30th day, the same measurements were done as the first one. Ccr was lower in cisplatin treated rats on the 5th day than that in control (0.10 +/- 0.03 vs 0.34 +/- 0.05 ml/min/100 g; p less than 0.01), thereafter tended to be recovered to the control level. On the other hand, 99mTc-DMSA uptake was lower than that of control on the 8th, 11th and 15th day (32.40 +/- 3.86, 32.56 +/- 1.19, 35.21 +/- 2.97 vs 39.84 +/- 2.23%, respectively; p less than 0.01). The discrepancy between 99mTc-DMSA uptake and Ccr was observed in the cisplatin-induced nephrotoxicity. 99mTc-DMSA uptake was suggested to be a reliable indicator of a renal function in a different way from Ccr.

[Assessment of 99mTc-DMSA renography and uptake compared with creatinine clearance in rats with drug-induced nephrotoxicity--I. Gentamicin-induced nephrotoxicity].

For evaluation of technetium-99m dimercaptosuccinic acid (99mTc-DMSA) renal uptake as an absolute renal function, 99mTc-DMSA uptake was compared with endogenous creatinine clearance (Ccr) in gentamicin-induced nephrotoxicity. Gentamicin (40 mg/kg/day) was given subcutaneously to male Wistar rats for periods of 3, 6, 9 and 12 days. On the next day, the renography was performed 2 hours following intravenous injection of 99mTc-DMSA and Ccr was measured. On the 7th day, 99mTc-DMSA uptake was significantly lower in the treated rats than that in control (32.27 +/- 0.92 vs 39.84 +/- 2.24%; p less than 0.01), but Ccr did not change (0.37 +/- 0.02 vs 0.34 +/- 0.05 ml/min/100 g; NS). On the 1st, 2nd, 4th and 8th day after single subcutaneous injection of 80 mg of gentamicin, 99mTc-DMSA uptake was measured and the histological examination was done. On the 4th day, 99mTc-DMSA uptake was significantly lower than that on the 1st day (32.32 +/- 3.00 vs 38.91 +/- 1.95%; p less than 0.01) and microscopic examinations revealed that eosinophilic granular degenerations were evident in the renal cortex. The present study suggests that 99mTc-DMSA uptake reduces earlier than Ccr in gentamicin-induced nephrotoxicity and 99mTc-DMSA uptake is a reliable indicator in the evaluation of a renal function in drug-induced nephrotoxicity.

Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects.

The correlations of 11 indexes of heart rate variability were examined with pharmacologically determined cardiac vagal tone in 15 normal subjects at supine rest. After sympathetic influences by intravenous propranolol were eliminated, RR interval variability was measured for 10 minutes under controlled respiration (0.25 Hz), and cardiac vagal tone was determined as the decrease in mean RR interval following complete vagal blockade with atropine. Time domain indexes (standard deviation, coefficient of variance and mean successive difference) correlated strongly with vagal tone (r = 0.87, 0.81 and 0.92, respectively; p less than 0.001 for all). The same was true for frequency domain indexes for the high-frequency (0.25 Hz) component calculated both by autoregressive spectrum analysis (square root of power and coefficient of component variance) and by fast Fourier transform (mean amplitude) (r = 0.91, 0.85 and 0.86, respectively; p less than 0.0001 for all). However, frequency domain indexes for the low-frequency spectral component (0.03 to 0.15 Hz) correlated less strongly (r = 0.69, 0.55 and 0.70, respectively), and the fraction of power [power/(total power greater than 0.03 Hz)] of both components showed no correlation. Principal component analysis showed that the first 6 indexes with strong correlations contained solely the first principal component closely related to vagal tone, whereas the remaining 5 indexes also contained the second component unrelated to vagal tone. These results indicate that most of the time and frequency domain analyses in use provides an accurate and common measure of cardiac vagal tone at rest.

[Antitumor activity of FK973 for malignant gliomas and its assessment for normal brain cells].

FK973, a novel antitumor antibiotic, was obtained as a fermentation product of Streptomyces sandaensis. FK973 had excellent cytotoxic effects against in vitro cultured human glioblastomas, medulloblastomas, and murine glioma (203 glioma) cells. The antitumor effects were also well observed against ACNU resistant glioma cells. FK973 did not go through the blood-brain barrier. The median survival time (MST) of MG models treated with FK973 was 21 days. On the other hand, the MST of the control group was 15 days. In the in vitro assessment against neural disturbance, FK973 showed a little disturbance of murine brain cells but less toxic than ADM. In the in vivo neurotoxicity examination, FK973 showed no clear damage to the neural cells and myelin sheaths.

[Quantitative assessment of gastric mucosal bleeding in the development of acute gastric mucosal lesions in the rat and prophylactic effect of elcatonin].

Intraperitoneal injection of indomethacin (5, 10 and 20 mg/kg) caused acute gastric mucosal lesions in the conscious restrained rat and also hypersecretion of gastric acid. Cimetidine, an H2-receptor antagonist, was found to prevent gastric mucosal bleeding and acid secretion induced by indomethacin. Elcatonin at higher doses than 2.5 U/kg (0.5 microgram/kg) was effective for protecting the gastric mucosa against indomethacin irritation, and it inhibited acid output in response to this ulcerogen. The acid inhibitory effect of elcatonin might be implicated in its cytoprotective action.