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Biomedical subjects

Hiroyuki Watanabe

Publications and source records attributed to Hiroyuki Watanabe.

At least 55 records · Page 3Linked to original sources
PubMed2005

Tropisetron improves deficits in auditory P50 suppression in schizophrenia.

Physiological deficits in inhibition of the P50 auditory evoked potential in schizophrenia have been related to diminished expression of alpha7 nicotinic acetylcholine receptors. Diminished P50 inhibition is correlated with neuropsychological deficits in attention, one of the principal neurocognitive disturbances in schizophrenia. Nicotine administration improves P50 inhibition, presumably by achieving additional activation of these diminished receptors, but its toxicity and marked tachyphylaxis make it an ineffective therapeutic. Nicotine also has weak positive effects on several neurocognitive deficits in schizophrenia, which raises the possibility that the alpha7 nicotinic receptor is a clinically relevant therapeutic target that should be addressed by less toxic agents. Tropisetron, a drug already approved for clinical use outside the United States as an anti-emetic, is a partial agonist at alpha7 nicotinic receptors and an antagonist at 5-HT(3) receptors. As an initial proof-of-principle study, we determined that a single administration of tropisetron significantly improves P50 inhibition in schizophrenia. These data are consistent with biological activity at a pathophysiological mechanism in schizophrenia and support further trials of this drug as a possible therapeutic for neurocognitive deficits in schizophrenia.

Adult↗
PubMed2005

No changes in serum epidermal growth factor levels in patients with schizophrenia.

A recent report demonstrated that serum levels of epidermal growth factor (EGF) were significantly decreased in patients with schizophrenia, suggesting that impaired EGF signaling might be associated with the pathophysiology of schizophrenia. Our goal in the present study was to determine whether serum levels of EGF are altered in patients with schizophrenia. We found that serum levels of EGF in drug-naive (n = 15) or medicated patients (n = 25) with schizophrenia did not differ from those of age- and sex-matched normal controls (n = 40). However, we found a significant correlation between serum EGF levels and BPRS scores in the combined groups of patients. Therefore, our results do not support the claim that EGF plays a role in the pathogenesis of schizophrenia, but they suggest that EGF may serve as a state marker, that is, as an index of symptom-linked deficits.

Adult↗
PubMed2005

DFT vibrational calculations of rhodamine 6G adsorbed on silver: analysis of tip-enhanced Raman spectroscopy.

The tip-enhanced near-field Raman (TERS) bands of Rhodamine 6G (R6G), that we reported earlier [Chem. Phys. Lett. 2001, 335, 369.], are assigned on the basis of density-functional theory (DFT) calculations at the 6-311++G(d,p) level. The Raman and infrared intensities as well as frequencies of the vibrational modes are used for band assignments. These vibrational modes, in combination with characterization of resonant electronic transitions using time-dependent DFT calculations, predict spectral changes in resonant Raman and surface-enhanced resonant Raman scatterings of R6G. Moreover, the TERS spectra of R6G are analyzed in detail, where interactions between the tip and R6G molecules and their enhancement mechanisms are discussed. Finally, we propose a novel Raman spectroscopy technique capable of detecting molecular vibrations at sub-nanometer scale.

Adsorption↗
PubMed2005

Duct-narrowing chronic pancreatitis without immunoserologic abnormality: comparison with duct-narrowing chronic pancreatitis with positive serological evidence and its clinical management.

We reviewed the clinical features and clinical course of patients with duct-narrowing chronic pancreatitis who were negative for immunoserologic test results (n = 16) in comparison with the findings for serological test-positive patients (n = 20) in order to determine an adequate treatment for those who had typical morphology of autoimmune pancreatitis in the absence of immunoserologic abnormality. No significant differences were found between the two groups of patients in clinical profiles including associated autoimmune-related diseases, pancreatic histology, and response to steroid therapy. Of the seronegative patients, eight who showed an improvement in narrowing of the main pancreatic duct with steroid therapy and three who did no show an improvement or who relapsed after surgical resection without this therapy had stenosis of the common bile duct with increased levels of serum hepatobiliary enzymes, except for two patients with affected sites limited to the body or tail of the gland. For the remaining five patients, who showed an improvement in pancreatic duct changes or long-term remission after surgery without steroid administration, normal biochemistry test results for liver functions were obtained, with no abnormal cholangiographic findings in the three patients examined. Duct-narrowing chronic pancreatitis without immunoserologic abnormality overlaps in clinical features with that fulfilling the immunoserologic criteria for a diagnosis of autoimmune pancreatitis. In particular, the disease with bile duct involvement should be treated clinically as autoimmune pancreatitis, for which steroid therapy is recommended, even if an autoimmune mechanism is not demonstrated serologically.

Adult↗
PubMed2005

Comparison of cardiovascular responses between upright and recumbent cycle ergometers in healthy young volunteers performing low-intensity exercise: assessment of reliability of the oxygen uptake calculated by using the ACSM metabolic equation.

OBJECTIVES: To clarify (1) differences in cardiovascular response during low-intensity exercise in the upright versus the recumbent position, and (2) whether the oxygen uptake (V o 2 ) calculated by the American College of Sports Medicine (ACSM) metabolic equation reflects the actual V o 2 at low-intensity testing. DESIGN: Repeated-measures comparison study. SETTING: University research laboratory. PARTICIPANTS: Thirty-one healthy, young volunteers (age, 23+/-2y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Blood pressure, rate pressure product (RPP), V o 2 , oxygen pulse, carbon dioxide output (V co 2 ), and ventilatory equivalent (V e ) were measured during graded exercise testing using upright and recumbent cycle ergometers. The estimated V o 2 was calculated by using the ACSM metabolic equation. RESULTS: Systolic blood pressure, RPP, V o 2 , oxygen pulse, V co 2 , and V e at 15 or 30W were significantly higher in the recumbent position than in the upright one ( P <.05), however, no significant differences were observed at 50 and 70W. The estimated V o 2 during exercise was significantly higher than the actual one, at every level of intensity, from 15 to 70W ( P <.05). CONCLUSIONS: Cardiovascular responses should be carefully monitored even during low-intensity exercise using a recumbent cycle ergometer. The V o 2 estimated using the ACSM metabolic equation did not reflect the actual V o 2 during low-intensity exercise at 70W or less.

Adult↗
PubMed2005

Effects of diacylglycerol ingestion on postprandial hyperlipidemia in diabetes.

BACKGROUND: We previously reported that diacylglycerol (DAG) as compared with triacylglycerol (TAG) suppressed increases in postprandial lipids in healthy volunteers. This study was to investigate the effects of DAG on postprandial lipids, particularly remnant lipoproteins in diabetics. METHODS: Emulsified DAG oil or TAG oil with a fatty acid composition similar to DAG oil was orally administered (30 g fat/m2 of body surface) to moderately controlled six diabetics, with hemoglobin A1c (HbA1c) below 8%, after fasting for at least 12 h in a randomized crossover manner. Serum cholesterol and TAG, lipids in remnant-like particles (RLP), and other lipid parameters including serum ketone bodies were measured prior to and 2, 4, and 6 h after fat loading. RESULTS: DAG loading significantly suppressed increases in postprandial serum TAG and lipids in RLP as compared with TAG loading. The incremental area under the curve (IAUC) for serum TAG and that for lipids in RLP with DAG loading were also significantly smaller than those with TAG loading. However, changes in serum levels of insulin, free fatty acids, and ketone bodies during fat loading were essentially the same for DAG and TAG. CONCLUSIONS: This pilot study suggests that substituting DAG intake for TAG may be beneficial to moderately controlled diabetics due to its effect in reducing postprandial hyperlipidemia.

Blood Glucose↗
PubMed2005

A novel technique to detect total occlusion in the right coronary artery using retrograde flow by transthoracic Doppler echocardiography.

BACKGROUND: We hypothesized that detection of reverse flow in the distal right coronary artery (d-RCA) and the inferior septal branches (ISB) by transthoracic Doppler echocardiography (TTDE) would be useful for noninvasive diagnosis of the occluded right coronary artery (RCA). METHODS: Coronary angiography and TTDE were performed on 129 patients. Antegrade flows in the d-RCA and the ISB were defined as directions from the base to the apex in the posterior sulcus and from anterior to inferior in the inferior septum, respectively. Retrograde flow was defined as an inverse direction. RESULTS: Retrograde flow was obtained by TTDE in 14 patients (d-RCA:11, ISB:3) of 18 patients with occluded RCA. The sensitivity and the specificity for identification of occluded RCA were 100% and 97.8%, respectively. CONCLUSION: Detection of reverse flow in the d-RCA and the ISB using TTDE is a useful method for the noninvasive diagnosis of occluded RCA.

Aged↗
PubMed2005

Physiologic assessment of coronary artery stenosis without stress tests: noninvasive analysis of phasic flow characteristics by transthoracic Doppler echocardiography.

We evaluated the significance of the diastolic-to-systolic blood flow velocity ratio (DSVR) determined by transthoracic Doppler echocardiography, for a physiologic assessment of the severity of coronary stenosis without stress tests, as compared with thallium 201 single photon emission computed tomography. In 95 patients undergoing thallium 201 single photon emission computed tomography for coronary artery disease, the flow velocity in the distal left anterior descending coronary artery was obtained with transthoracic Doppler echocardiography. The mean and peak DSVR values were calculated using mean and peak coronary flow velocity. DSVR was successfully measured for 82 patients (86.3%), including 33 patients with reversible perfusion defects in the left anterior descending coronary artery territories. For predicting reversible perfusion defects in thallium 201 single photon emission computed tomography, the best cut-off points were 1.5 for mean DSVR (sensitivity 81.8%, specificity 85.7%) and 1.6 for peak DSVR (sensitivity 75.7%, specificity 83.6%). Noninvasive measurement of DSVR with transthoracic Doppler echocardiography provides physiologic estimation of the left anterior descending coronary artery stenosis severity at high success rate, without stress tests.

Coronary Circulation↗
PubMed2005

Effects of diacylglycerol administration on serum triacylglycerol in a patient homozygous for complete lipoprotein lipase deletion.

We investigated postprandial and long-term effects of dietary diacylglycerol (DAG) on serum triacylglycerol (TAG) levels in a 34-year-old man homozygous for complete lipoprotein lipase deletion (LPL deletion). In study 1, Three different oils (DAG, TAG, or medium-chain fatty acid TAG [MCT]) were ingested to examine differences in the postprandial serum TAG response. Postprandial serum TAG levels after DAG oil ingestion were lower than those after TAG oil ingestion and similar to those after MCT oil ingestion. In study 2, the patient was allowed to ingest ordinary cooking oil for 2 months and then DAG oil (containing 80% DAG; target, 20 g/d) for the next 3 months. During the test period, serum TAG levels were measured and dietary evaluations were performed every month. The patient was provided with dietary instruction and consultation at each clinical visit. Serum TAG levels were 1939 to 2525 mg/dL when he used ordinary cooking oil, 1926 to 1173 mg/dL when he used ordinary cooking oil together with DAG oil, and 749 mg/dL when he used DAG oil alone. The TAG intake decreased from 86.9 to 43.0 g and the DAG intake increased from 0.9 to 12.4 g during the study period. Subsequently, 45 g DAG oil (equivalent to 36 g DAG) per day was consumed, and the serum TAG level increased to 2195 mg/dL. Although there was a positive correlation between the TAG intake and serum TAG levels during the period of DAG oil use (P < .01, y = 33.7x - 583.1), there was no such correlation between DAG oil intake and serum TAG levels. These results suggested that substitution of 12.0 g/d DAG (equivalent to 15 g DAG oil) for TAG oil had the same effect as reducing TAG oil consumption for controlling the serum TAG levels in an LPL-depleted patient with hypertriglyceridemia. In conclusion, the results of study 1 and study 2 demonstrate that DAG oil might be replaced by MCT oil as cooking oil for those with LPL deletion.

Adult↗
PubMed2005

Enhanced antinociception by intracerebroventricularly and intrathecally-administered orexin A and B (hypocretin-1 and -2) in mice.

Orexins are neuropeptides located exclusively in neurons of the lateral hypothalamic area, which send projections to most monoaminergic nuclei, such as noradrenergic locus coeruleus, dopaminergic ventral tegmental areas, and histaminergic tuberomammillary nuclei. The present work was carried out to examine the role of orexins in nociception in mice. C57BL/6 mice were administered with orexin A and B intracerebroventricularly (i.c.v.), intrathecally (i.t.) and subcutaneously (s.c.) to reveal the sites of action of these peptides and to examine the pain thresholds using four kinds of nociceptive tasks. Orexins showed antinociceptive effects in all four types of assays for thermal (hot-plate, tail-flick, paw-withdrawal), mechanical (tail-pressure), chemical (formalin, capsaicin and abdominal stretch) nociceptions and nociceptin-induced behavioral responses, when administered i.c.v. or i.t., whereas the s.c. administration was ineffective. The antinociceptive effects of orexin A were more remarkable than those of orexin B. The i.c.v. administration of orexin A was as effective as, or more potent than the i.t. administration. The effects of orexin A were completely blocked by adenosine type 1 receptor antagonists, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and theophylline, but not by naloxone, suggesting a possible involvement of the adenosine-containing neurons and/or the adenosine pathway in these orexin actions. The i.c.v. administration of nociceptin had no significant effects on orexin expression in the brain and spinal cord. The present findings suggest that orexins have an antinociceptive role in at least four different types of pains, probably acting on both the brain and spinal cord.

Analgesics↗
PubMed2005

Increased midkine levels in sera from patients with Alzheimer's disease.

Midkine (MK) is a heparin binding growth factor and promotes growth, survival and migration of various cells including neurons. It is also known to accumulate in senile plaques of patients with Alzheimer's disease (AD). To investigate the involvement of serum MK in the pathophysiology of AD, serum MK levels were determined in patients with AD (n=36) and age- and sex-matched healthy controls (n=32), using an enzyme-linked immunosorbent assay (ELISA). The serum MK values of the patients with AD (median 560 and interquartile range (500-755) pg/ml) were significantly (U=278.5, P=0.0003, Mann-Whitney U-test) higher than those of the controls (median 500 and interquartile range (385-520) pg/ml). Moreover, 17 patients (47.2%) had abnormally high values of more than 600 pg/ml, but no controls (0%) did. There was no correlation between serum MK level and the mini mental state examination (MMSE) score in the patients. The demonstration of elevated MK levels in sera of patients with AD may contribute toward an understanding the pathophysiology of this disease, and provide a novel potential therapeutic strategy for decreasing neuronal damages in patients with AD. We found that serum MK levels in patients with AD were increased in comparison with those of normal controls.

Aged↗
PubMed2005

Long-term sucrose-drinking causes increased body weight and glucose intolerance in normal male rats.

The current epidemic of diabetes likely reflects marked changes in environmental factors, although genetic susceptibility plays a powerful role in the occurrence of diabetes in certain populations. We investigated whether long-term sucrose-drinking causes hyperglycaemia in male Wistar-Imamichi littermates (n 32), which are not genetically susceptible to diabetes or obesity. Each litter was divided equivalently into two groups, the sucrose group and the control group. The sucrose group received 300 g/l sucrose water and the control group received regular water until 42 weeks of age. Rats were weighed every 1 or 2 weeks. Oral glucose tolerance tests were performed at 28 and 36 weeks of age. Plasma glucose and insulin concentrations were measured. Body weights were significantly greater in the sucrose group than in the control group in 18-week-old rats (P<0.05), and the difference between the two groups reached 163 g by the end of the study (P<0.01). The 120 min post-load plasma glucose concentration in the sucrose group was 11.4 (SD 2.8) mmol/l in 28-week-old rats and 12.7 (SD 2.2) mmol/l in 36-week-old rats, while that of the control group remained approximately 7.3-7.7 mmol/l. In the sucrose group, the plasma insulin peak occurred 30 min post-load at 28 weeks of age; but the peak disappeared and hyperinsulinaemia was prolonged at 36 weeks of age. In conclusion, long-term sucrose-drinking causes increased body weight and glucose intolerance in normal male rats.

Animals↗
PubMed2005

Expression of mesothelin mRNA in pure pancreatic juice from patients with pancreatic carcinoma, intraductal papillary mucinous neoplasm of the pancreas, and chronic pancreatitis.

OBJECTIVES: In the gene expression analysis of pancreatic carcinoma (PCa) using serial analysis of gene expression (SAGE) according to Ryu et al, the tag for the mesothelin mRNA transcript was present in 7 of 8 SAGE libraries derived from PCa but not in the 2 SAGE libraries derived from normal pancreatic duct epithelial cells. Mesothelin mRNA expression was confirmed with in situ hybridization in all 4 resected primary PCa tumors and with RT-PCR in 18 of 20 PCa cell lines, whereas mesothelin protein expression was confirmed with immunohistochemistry in all 60 resected primary PCa tissues by Argani et al. We evaluated mesothelin mRNA expression in pure pancreatic juice (PPJ) obtained from patients with PCa, chronic pancreatitis (CP), and intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: We evaluated mesothelin mRNA expression in the PPJ obtained from 21 patients with PCa, 22 with CP, and 11 with IPMN with reverse transcriptase PCR (RT-PCR). The PCR products were analyzed with agarose gel electrophoresis. DNase I treatment before RT-PCR and direct sequencing of the RT-PCR bands were performed for the analysis of the RT-PCR bands. RESULTS: Two products, of 308 and 226 bp, were obtained with RT-PCR, and the 308-bp RT-PCR product was confirmed as being that derived from the genomic DNA by direct DNA sequencing. Mesothelin mRNA expression was discovered using RT-PCR in 11 (52%) of 21 patients with PCa, 5 (45%) of 11 with IPMN, and 3 (14%) of 22 with CP. Fisher's exact test revealed significant differences between PCa and CP for mesothelin mRNA (P < 0.01). Moreover, the RT-PCR product (226 bp) of mesothelin mRNA in the PPJ samples with PCa was generally stronger than that in the PPJ samples with IPMN. CONCLUSION: Expression of mesothelin mRNA in PPJ was not strictly specific to PCa and was apt to be stronger in PCa than in IPMN. Quantitative detection of mesothelin mRNA in PPJ may have potential diagnostic implications for pancreatic tumors.

Adenocarcinoma, Mucinous↗
PubMed2005

Freehand three-dimensional echocardiography with rotational scanning for measurements of left ventricular volume and ejection fraction in patients with coronary artery disease.

BACKGROUND: Measurement of left ventricular (LV) volumes and ejection fraction (EF) is important in managing patients with coronary artery disease (CAD). Introduction of free-hand three-dimensional echocardiography (3DE) system which is equipped with small magnetic tracking system and average rotational geometry for LV volumes may provide easy and accurate quantification of LV systolic function in CAD patients. PURPOSE: To evaluate the feasibility and accuracy of LV volumes and EF measurement by free-hand 3DE with rotational geometry in patients with CAD. METHODS AND RESULTS: The study subjects consisted of consecutive 25 patients with CAD who were scheduled for quantitative gated single-photon emission computed tomography (QGS). LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF were determined by conventional two-dimensional echocardiography (2DE), 3DE, and QGS. Three-dimensional echocardiography data acquisition and analysis were possible in 22 of 25 subjects (feasibility 88%). In this 3DE system, image acquisition time was 2 minutes, and 5 minutes were needed for off-line analysis of LV volumes and EF. Correlations and the limits of agreement between 3DE and QGS (r = 0.97, 0.0 +/- 9.1 ml for EDV, r = 0.99, 0.0 +/- 5.0 ml for ESV, and r = 0.97, 0.5 +/- 3.3% for EF, respectively) were superior to those between 2DE and QGS (r = 0.85, 12.6 +/- 26.8 ml for EDV, r = 0.85, 9.7 +/- 26.1 ml for ESV, and r = 0.90, -1.3 +/- 6.9% for EF, respectively). Inter- and intra-observer variabilities of 3DE were smaller than that of 2DE (5% vs 10%, 5% vs 10% for EDV, 6% vs 13%, 5% vs 9% for ESV, and 4% vs 11%, 4% vs 6% for EF, respectively). CONCLUSION: Three-dimensional echocardiography using magnetic tracking system and average rotational geometry offered a feasible and accurate method for quantification of LV volumes and EF in patients with CAD.

Aged↗
PubMed2005

Sporadic fatal insomnia with spongiform degeneration in the thalamus and widespread PrPSc deposits in the brain.

We report a case of human prion disease of 29 months duration in a 74-year-old Japanese man. The disease started with progressive sleeplessness and dementia. MRI showed gradually progressive cerebral atrophy. Neuronal loss, spongiform change and gliosis were evident in the thalamus and cerebral cortex, as well as in the striatum and amygdaloid nucleus. In the cerebellar cortex, mild-to-moderate depletion of Pukinje cells and spongiform change were observed. Mild neuronal loss in the inferior olivary nucleus was also seen. Immunohistochemistry revealed widespread perivacuolar deposits of abnormal prion protein (PrPsc) in the cerebral cortex, thalamus, basal ganglia, and brainstem, and minimal plaque-like deposits of PrPSc in the cerebellar cortex. In the cerebellar plaque-like deposits, the presence of amyloid fibrils was confirmed ultrastructurally. The entire pathology appeared to lie halfway between those of CJD and fatal insomnia, and further demonstrated the relationship between spongiform degeneration and PrPSc deposits, especially in the diseased thalamus. By immunoblotting, the thalamus was shown to contain the lowest amount of PrPSc among the brain regions examined. The PrPSc of type 2, in which the ratio of the three glycoforms was compatible with that of sporadic fatal insomnia (MM2-thalamic variant) reported previously, was also demonstrated. Analysis of the prion protein gene (PRNP) showed no mutation, and homozygosity for methionine at codon 129. In conclusion, we considered that this patient had been suffering from sporadic, pathologically atypical fatal insomnia.

Aged↗
PubMed2005

Impaired coronary circulation in patients with apical hypertrophic cardiomyopathy: noninvasive analysis by transthoracic Doppler echocardiography.

OBJECTIVES: We designed this study to examine the characteristics of coronary circulation in patients with apical hypertrophic cardiomyopathy (ApHCM) using noninvasive transthoracic Doppler echocardiography (TTDE). BACKGROUND: Recent advances in TTDE have allowed noninvasive assessment of coronary circulation by the measurement of coronary flow velocity (CFV) patterns and coronary flow velocity reserve (CFVR). However, there have been no previous studies evaluating coronary circulation in ApHCM. METHODS: We analyzed CFV and CFVR in the left anterior descending coronary artery (LAD), and apical wall thickness in the left ventricle, in 10 ApHCM subjects and 10 control subjects. Mean diastolic velocity (MDV) and time from the beginning of diastole to peak velocity (TPV), and CFVR, defined as a ratio of drug-induced hyperemic to basal MDV, were measured. RESULTS: At baseline, MDV was higher, and TPV was longer, in ApHCM subjects than in control subjects (29 +/- 5.7 versus 19 +/- 6.5 cm/sec; p < 0.01 and 5.2 +/- 1.0 versus 3.5 +/- 0.6 msec; p < 0.005, respectively). CFVR in ApHCM subjects was significantly lower than in control subjects (1.9 +/- 0.4 versus 3.1 +/- 0.8; p < 0.005). CFVR and basal MDV in ApHCM subjects showed significant correlations with apical/posterior wall thickness ratio [CFVR; r =-0.84, p < 0.01 and MDV; r = 0.74, p < 0.05, respectively]. CONCLUSION: Noninvasive coronary flow assessment by TTDE revealed an impaired coronary circulation with reduced CFVR, high MDV at baseline and prolonged TPV. These results suggest that these characteristics of coronary circulation may provide an additional index for the assessment of ApHCM.

Adenosine Triphosphate↗
PubMed2005

QT PRODACT: sensitivity and specificity of the canine telemetry assay for detecting drug-induced QT interval prolongation.

The purpose of this investigation was to define the sensitivity and specificity of the canine telemetry assay for detecting drug-induced QT interval prolongation. Data from twelve studies generated in the QT PRODACT project were used in this investigation. The study design was a 4x4 Latin square cross-over design and included the following drugs: MK-499, E-4031, terfenadine, haloperidol, cisapride, bepridil, propranolol, diphenhydramine, captopril, verapamil, amoxicillin, and ciprofloxacin. The estimated root squared error of the model, which estimated the slope of the QT-RR relationships for each animal, for all dogs during the pre-dosing period was 5.45%. Using the QT-RR model, the sensitivity and specificity in each cutoff value that judges QT prolongation were estimated based on the experiment errors and measurement errors in the 12 studies. When the cutoff value was 5%, the sensitivity in 10% prolongation was 0.978 and the specificity in 0% was 0.996. In conclusion, it was judged that a 5% cutoff value for changes in heart rate corrected QT interval using the canine telemetry assay is practical, and the sensitivity and specificity of the telemetry assay are very high when using the analytical method presented here. Based upon this information, the canine telemetry assay using the individual subject heart rate correction model is recommended as a sensitive test system for the in vivo assessment of risk for QT interval prolongation.

Animals↗