Biomedical subjects

W C Shyu

Publications and source records attributed to W C Shyu.

At least 37 records · Page 2Linked to original sources

PubMed1998

Consistency between preference and use of long-term care among caregivers of stroke survivors.

Effective arguments have been made for the importance of expanded attention to understanding how family preferences influence decisions to choose long-term care. The effects of preference on the utilization of long-term care deserve further research, especially on a longitudinal basis. The family members of 582 first-time stroke patients from the neurology departments of four teaching hospitals in Taiwan were categorized into two groups based on their attitudes toward type of long-term care, i.e., a preference for nursing home care (n1 = 324) or a preference for home care (n2 = 258). The consistency rate between preference and utilization of the type of long-term care was estimated by the division of number of families preferring one type of long-term care by the number of families actually utilizing the services preferred. Results indicated that the consistency rate for those with nursing home preference was 8.3% while the consistency rate for those with home care preference was 94.2%. Accessibility of nursing home facilities near family residences was significantly associated with whether those preferring nursing home services actually utilized them, and the odds ratio was 20.8. The family manpower available for caregiving at home was tremendously associated with whether families utilized home care when home care was preferred; the odds ratio was 33.3. The preference for the type of long-term care was a strong predictor of the utilization when home care was preferred, yet not when a nursing home was preferred. The low consistency between preference and utilization for nursing homes preferred is due to the low accessibility of nursing home facilities in Taiwan. How to provide sufficient support to families for caregiving at home, and how to deal with the barrier of accessibility to nursing home services should be two major concerns for those who are planning and operating the long-term care system and for those trying to design institutional services and noninstitutional services as alternatives.

Caregivers↗

PubMed1998

Pharmacokinetic assessment of the sites of first-pass metabolism of BMS-181101, an antidepressant agent, in rats.

The relative contribution of the gut and the liver to the first-pass metabolism of BMS-181101 (3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]propyl]-5-fluoro-1H-ind ole dihydrochloride), a potential antidepressant agent, has been evaluated in rats. Nine male Sprague-Dawley rats were divided into three groups of three and each rat received a single 20 mg kg(-1) dose of [14C]BMS-181101 via a 30 min constant-rate intravenous infusion, a 30-min constant-rate intraportal infusion or oral gavage. Serial blood samples were collected for 8 h after dosing and plasma was analysed for unchanged BMS-181101 and total radioactivity. Extraction ratios for BMS-181101 by the gut and liver were calculated on the basis of ratios of the area under the plasma BMS-181101 concentration-time curve. The gut had a high intrinsic capacity for metabolizing BMS-181101-extraction ratios were 93% and 10% for the gut and liver, respectively. After oral administration BMS-181101 is sequentially exposed to the gut then the liver. As a result, the contribution of the gut to the overall first-pass effect (ca. 93%) was significantly greater than that of the liver (ca. 0.7%). The estimated total first-pass effect of 94% for BMS-181101 in rats is in excellent agreement with the observed absolute oral bioavailability of 6%. These results clearly illustrate the importance of metabolic activity in the gut for orally administered BMS-181101.

Administration, Oral↗

PubMed1998

Biotransformation of irbesartan in man.

The metabolism of irbesartan, a highly selective and potent nonpeptide angiotensin II receptor antagonist, has been investigated in humans. An aliquot of pooled urine from healthy subjects given a 50-mg oral dose of [14C]irbesartan was added as a tracer to urine from healthy subjects that received multiple, 900-mg nonradiolabeled doses of irbesartan. Urinary metabolites were isolated, and structures were elucidated by mass spectroscopy, proton NMR, and high-performance liquid chromatography (HPLC) retention times. Irbesartan and the following eight metabolites were identified in human urine: (1) a tetrazole N2-beta-glucuronide conjugate of irbesartan, (2) a monohydroxylated metabolite resulting from omega-1 oxidation of the butyl side chain, (3, 4) two different monohydroxylated metabolites resulting from oxidation of the spirocyclopentane ring, (5) a diol resulting from omega-1 oxidation of the butyl side chain and oxidation of the spirocyclopentane ring, (6) a keto metabolite resulting from further oxidation of the omega-1 monohydroxy metabolite, (7) a keto-alcohol resulting from further oxidation of the omega-1 hydroxyl of the diol, and (8) a carboxylic acid metabolite resulting from oxidation of the terminal methyl group of the butyl side chain. Biotransformation profiles of pooled urine, feces, and plasma samples from healthy male volunteers given doses of [14C]irbesartan were determined by HPLC. The predominant drug-related component in plasma was irbesartan (76-88% of the plasma radioactivity). None of the metabolites exceeded 9% of the plasma radioactivity. Radioactivity in urine accounted for about 20% of the radiolabeled dose. In urine, irbesartan and its glucuronide each accounted for about 5 to 10% of the urinary radioactivity. The predominant metabolite in urine was the omega-1 hydroxylated metabolite, which constituted about 25% of the urinary radioactivity. In feces, irbesartan was the predominant drug-related component (about 30% of the radioactivity), and the primary metabolites were monohydroxylated metabolites and the carboxylic acid metabolite. Irbesartan and these identified metabolites constituted 90% of the recovered urinary and fecal radioactivity from human subjects given oral doses of [14C]irbesartan.

Antihypertensive Agents↗

PubMed1998

Analysis of costs borne by families of patients hospitalized for stroke.

BACKGROUND: Studies focusing on the economic impact of cancer on families have emphasized that costs of chronic disease are substantial for patients and their families. However, little effort has been devoted to measuring the costs of care for families of patients hospitalized with stroke. METHODS: A total of 215 stroke patients and their families from four teaching hospitals in the Taipei metropolitan area were monitored from the date of the patient's admission to hospital until the date of discharge. The value of labor contributed by families was estimated by assigning the current monetary market rate of providing health aide to the time families spent caring for patients in hospital. Lost earnings of patients and families, expenditure for medical care, and expenses for food, clothes, adult diapers, transportation and other miscellaneous items were determined and summed to arrive at the total family cost of providing care. RESULTS: The average cost of care for one family per inpatient day was NT$4,358.20. A total of 98.6% of the families incurred labor costs, which accounted for about half of family costs for providing care. Hospital bills accounted for almost 19% of total family costs. The income loss for families and patients accounted for about 25% of total family costs. Expenses for food, clothes, transportation, diapers and other illness-related miscellaneous items accounted for about 12% of total family costs. Multiple regression analyses demonstrated that the number of family members involved in giving care and the length of stay are important predictors for the total cost of care. Average total family costs per day increased by 24.3% when an additional family member was involved in providing care. Total family costs increased 2.5% for each hospital day. CONCLUSIONS: If direct and indirect nonmedical costs are not included in the total cost calculation for providing hospital care to stroke patients, the economic impact of care on families is likely to be underestimated.

Adult↗

PubMed1997

The pharmacokinetics of butorphanol and its metabolites at steady state following nasal administration in humans.

The single-dose and steady state pharmacokinetics of butorphanol and its metabolites, hydroxybutorphanol (HO-B) and norbutorphanol (NOR-B), were studied in nine healthy male volunteers. Each subject received a single 1 mg dose of butorphanol on days 1 and 6, and a 1 mg dose every 6 h (q6h) on days 2-5, via nasal administration. Serial blood and urine samples were collected for 24 h after the first dose on day 1 and for 72 h at steady state on day 6. Plasma and urine samples were analyzed for free and conjugated butorphanol, HO-B, and NOR-B. The plasma samples were analyzed using validated gas chromatography-electron capture negative chemical ionization-mass spectrometric methods and the urine samples were analyzed using a validated HPLC procedure. In the plasma, conjugated metabolites were not detected and only trace amounts of NOR-B were present. Therefore, pharmacokinetic parameters could not be estimated for NOR-B and conjugated metabolites. AUC0-->infinity of butorphanol after the first dose and AUC0-->tau at steady state were not statistically different, indicating that the kinetics of butorphanol were not significantly altered after repeated dosing. Steady state levels of butorphanol were attained within 3 days (d) of q6h dosing and the accumulation index was 1.2 for butorphanol. Due to a relatively long t1/2 of 15 h of HO-B compared to the dosing interval (q6h), the accumulation index was 6.0 for this metabolite. The evaluation of the molar plasma concentration ratio of HO-B to butorphanol as a function of time revealed that HO-B exhibits elimination-rate-limited kinetics. Similarly to butorphanol, steady state levels of HO-B were attained within 3 d of q6h dosing.

Administration, Intranasal↗

PubMed1997

Lack of effect of food on the steady state pharmacokinetics of BMS-181101, an antidepressant, in healthy subjects.

The effect of food on the pharmacokinetics of BMS-181101, a new anti-depressant under development, was investigated in 12 healthy male volunteers at steady state. Each subject received a 15 mg oral dose of BMS-181101 twice a day (q 12 h) for 11 days and a morning dose of BMS-181101 on day 12. Six subjects were randomly assigned to receive BMS-181101 under fasted conditions from days 1 to 6 and then crossed over to fed conditions from days 7 to 12. The other six subjects received the reverse conditions, fed for days 1-6 and fasted for days 7-12. Serial blood samples were collected up to 12 h on days 6 and 12 following the administration of the morning dose. In addition, trough blood samples were collected on days 4, 5, 10, and 11 prior to the morning dose. Plasma samples were analyzed for intact BMS-181101 using a validated high-performance liquid chromatography method with an electrochemical detector. BMS-181101 was well tolerated both with and without ingestion of food. The statistical evaluation of the Cmin values indicated that steady state of BMS-181101 was achieved by the fourth day of dosing regardless of whether the subject was fasted or fed. When BMS-181101 was administered with food, Cmax was reduced by about 25% and tmax was prolonged by 1 h. However, AUCtau, t1/2, and time to attain steady state of BMS-181101 were not altered by ingestion of food. In summary, BMS-181101 can be given with food without adversely impacting the safety or pharmacokinetic profiles of the drug.

Administration, Oral↗

PubMed1997

Pharmacokinetic interaction between butorphanol nasal spray and oral metoclopramide in healthy women.

The pharmacokinetics of butorphanol nasal spray, with and without the coadministration of metoclopramide, were studied in 24 healthy women. In this crossover study all volunteers received 3 treatments: a single, 1-mg dose of butorphanol nasal spray, a single, 10-mg oral dose of metoclopramide, and a combination of a single, 1-mg dose of butorphanol nasal spray and a single, 10-mg oral dose of metoclopramide. There was at least a one-week washout period between sessions. Serial blood samples were collected and plasma samples analyzed using a validated radioimmunoassay to determine the concentration of butorphanol, or a high-performance liquid chromatography/ultraviolet procedure was used to determine the concentration of metoclopramide. There were no statistically significant differences in the pharmacokinetic parameters, Cmax, tmax, AUC, and t1/2, for butorphanol with or without metoclopramide. Similarly, except for a delay in tmax of metoclopramide with coadministration of butorphanol, the pharmacokinetic parameters of metoclopramide were not significantly different between two treatments. Thus, the pharmacokinetics of both butorphanol and metoclopramide were not significantly altered when administered in combination. The incidence of nausea/vomiting after butorphanol administration was substantially reduced by coadministration of metoclopramide. Based on the pharmacokinetic and safety results, it can be concluded that butorphanol nasal spray and metoclopramide can be administered in combination without altering the dose regimen of either drug.

Administration, Oral↗

PubMed1997

Effects of age, gender, and diurnal variation on the steady-state pharmacokinetics of BMS-181101, an antidepressant, in healthy subjects.

OBJECTIVES: To investigate the effects of age, gender, and diurnal variation on the safety, tolerability, and steady-state pharmacokinetics of BMS-181101, an antidepressant, in humans. METHODS: This was a multiple-dose parallel-design study in 51 healthy subjects (12 young and 12 elderly men and 12 young and 15 elderly women). Each subject received a 15 mg oral dose of BMS-181101 every 12 hours on days 1 through 6 and one dose on day 7. After the evening dose on day 6 and morning dose on day 7, serial blood samples were collected at specified times after administration. Plasma was analyzed for BMS-181101 with use of an HPLC method. RESULTS: Male subjects tolerated BMS-181101 better than female subjects. The mean values for area under the plasma concentration-time curve over the dosing interval tau (AUC tau; 58.8 to 102.4 ng.hr/ml) and elimination half-life t1/2; 5.7 to 10.4 hours) for the elderly subjects were significantly greater than those for the young subjects (39.0 to 64.3 ng.hr/ml and 3.2 to 4.5 hours). The mean values for peak plasma concentration (Cmax; 14.7 to 25.2 ng/ml) and AUC tau (52.4 to 102.4 ng.hr/ml) for the women were significantly greater than those for the men (9.08 to 15.3 ng/ml and 39.0 to 73.6 ng.hr/ml). The mean values for Cmax (14.7 to 25.2 ng/ml) and AUC tau (54.8 to 102.4 ng.hr/ml) on the morning of day 7 were significantly greater than those after the evening dose on day 6 (9.08 to 17.3 ng/ml; 39.0 to 83.4 ng.hr/ml). CONCLUSIONS: An initial lower dose or appropriate titration of daily doses of BMS-181101 may be necessary for the treatment of elderly and female subjects, and the pharmacokinetics of BMS-181101 exhibited significant diurnal effects.

Adult↗

PubMed1997

Application of chromosome 4q35-qter marker (pFR-1) for DNA rearrangement of facioscapulohumeral muscular dystrophy patients in Taiwan.

Facioscapulohumeral muscular dystrophy (FSHD) has been found to be linked to chromosome 4qter. A chromosome 4q35-ter marker, pFR-1 (subclone of the cosmid c51), has been recently isolated and used as a probe for mapping near, or within, the FSHD gene. To examine FSHD-associated DNA rearrangements in the Taiwan population, we used the pFR-1 probe to perform Southern blot analysis on 142 individuals, including 32 FSHD patients within 9 autosomal dominant families, five sporadic FSHD patients from 4 families (include one pair of twins), three sporadic scapuloperoneal syndrome (SPS) patients and two sporadic polymyositis patients with their unaffected parents, and 29 healthy controls. In 29 healthy individuals, 3 SPS and 2 polymyositis patients with their families, probe pFR-1 analysis revealed that all had polymorphic restriction fragments that were larger than 28 kb in length. All but 1 FSHD-affected individual had specific smaller EcoRI fragments (ranging in size from 10.5 to 27 kb). Two point linkage analysis between pFR-1 and the FSHD locus provided significant evidence for FSHD linkage (Z(max)=6.84). A similar smaller fragment was also present in 5 sporadic patients, while this smaller fragment could not be found in one of their parents. Identical EcoRI restriction fragment length polymorphism (RFLP) patterns linked to FSHD were shown in the monozygotic twins, even though they showed extreme variability in the expression of FSHD. We conclude that the pFR-1 probe is a tightly linked marker of FSHD and can be used to detect most DNA rearrangements associated with this disease in the Taiwan population. However, the same RFLP patterns may represent extreme variability in the expression of the FSHD gene.

Adolescent↗

PubMed1997

Quantitative assessment of hepatitis C virus RNA by polymerase chain reaction and a digoxigenin detection system: comparison with branched DNA assay.

A method for quantifying hepatitis C virus (HCV) RNA in serum using reverse transcription-polymerase chain reaction (RT-PCR) followed by slot-blot hybridization with a specific, digoxigenin-labeled probe was developed. Using RNA synthesized from cloned HCV cDNA as a standard, serum concentration of HCV RNA above 10 copies/ml can be quantitatively determined. To compare this method with branched DNA (bDNA) assay, 45 serum samples from 26 patients with newly acquired acute hepatitis C (n = 16) or hepatitis C with acute exacerbation (n = 10) were submitted to both assays. HCV RNA in 30 (67%), 12 (27%) and three (6.7%) samples can be quantitatively determined by both, either and none of the two assays, respectively. Using a standardized qualitative HCV RNA detection test (Amplicor HCV test) as a reference, 1 and 0 false positive results were found by bDNA and this assay, respectively. This quantitative assay using RT-PCR and a digoxigenin detection system was comparable to bDNA assay. Since a false positive result was rarely found, this technique can be used as a first line test to screen a large number of samples rapidly and economically.

Acute Disease↗

PubMed1997

A sensitive enzyme immunoassay for the quantitation of human CTLA4Ig fusion protein in mouse serum: pharmacokinetic application to optimizing cell line selection.

A sensitive, accurate, and precise enzyme immunoassay (EIA) for the quantitation of human CTLA4Ig in mouse serum was validated. The EIA method employed a technique in which a monoclonal anti-CTLA4 antibody was adsorbed onto 96-well polystyrene microtiter plates and used to capture the CTLA4Ig in mouse serum samples. The captured CTLA4Ig was then detected using a goat anti-human IgGFc antiserum conjugated to the enzyme horseradish peroxidase. The validation included assessments of method accuracy and precision, range of reliable response, lower limit of quantitation (LLQ), inter-analyst robustness, storage stability in mouse serum and assay specificity. The results indicate that this validated assay is precise, accurate, and reproducible. This EIA has a range of reliable response in 10% mouse serum of 0.14-4.58 ng ml-1 resulting in a 100% serum equivalent curve of 1.4-45.8 ng ml-1. Assessment of individual standard curve variations indicated a reproducible response with R2 values of > or = 0.995. The LLQ was established at 1.4 ng ml-1. The accuracy and precision estimates, based on the quality control values, were within 3.8% and 5.2% respectively, for CTLA4Ig. Stability of CTLA4Ig was established in mouse serum for 5 days at both 4 degrees C and room temperature, for 2 months at -70 degrees C and through five freeze-thaw cycles. This validated assay was successfully employed in the assessment of pharmacokinetic characteristics of CTLA4Ig in mice and to aid in the selection of an optimal CTLA4Ig-producing cell line.

Abatacept↗

PubMed1997

Assessment of dose proportionality, absolute bioavailability, and immunogenicity response of CTLA4Ig (BMS-188667), a novel immunosuppressive agent, following subcutaneous and intravenous administration to rats.

PURPOSE: The objectives of this study were: to delineate the pharmacokinetics of CTLA4Ig in rats after single and multiple intravenous (IV) and subcutaneous (SC) doses; to assess the relationship of the pharmacokinetic parameters of CTLA4Ig vs dose; to calculate the SC absolute bioavailability; and to assess the antibody response of CTLA4Ig. METHODS: A total of 48 (24 male and 24 female) Sprague Dawley rats were divided into eight treatments with 3 rats per gender in each group: a single dose of 10, 80, or 200 mg/kg of CTLA4Ig given either IV or SC and a repeated dose of 10 mg/kg (once every other day for 7 doses over 13 days) given either SC or IV. Serial blood samples were collected up to 43 days after single dose administration and up to 50 days following the administration of the last multiple dose on day 13. The serum concentration of CTLA4Ig and anti-CTLA4Ig antibodies were measured using ELISA assays. RESULTS: After single IV doses, Cmax and AUCinf increased in a dose proportional manner; CL appeared to be dose independent, while both Vss and T1/2 increased as the administered dose increased. Following single SC doses, Cmax and AUCinf increased in a linear manner but not proportionally; mean Tmax values were prolonged but similar among the three dose levels, while T1/2 increased as the administered dose increased. The absolute SC bioavailability of CTLA4Ig decreased as the dose increased from 10 (62.5%), 80 (55.7%), and 200 mg/kg (41.1%). Comparison of the AUCtau values between the first and last doses suggested an accumulation (3.1-4.7) of CTLA4Ig. However, regardless of the route of dosing, AUCtau after the last dose were comparable to AUCinf values following the single dose. Anti-CTLA4Ig antibodies were detected at the 10 mg/kg dose level after single or multiple doses for both routes of administration. However, regardless of single or multiple doses, antibody titers were relatively greater for the SC compared to the IV administration. CONCLUSIONS: The key findings of this study were: (i) the elimination characteristics of CTLA4Ig were comparable between the SC and IV routes; (ii) the repeated dosing did not alter the pharmacokinetics of CTLA4Ig; (iii) the SC absolute bioavailability tended to decrease as the administered dose increased; and (iv) a greater formation of anti-CTLA4Ig antibodies was observed after SC compared to IV at a single 10 mg/kg dose level; however, after multiple dosing, the formation of antibodies from either of the two routes was relatively slower, and (v) during the study period, no antibodies were observed at either the 80 or 200 mg/kg dose levels regardless of the route of administration.

Abatacept↗

PubMed1997

A cost-effectiveness analysis of home care and community-based nursing homes for stroke patients and their families.

A prospective study designed for 336 hospitalized patients with stroke and their families, who were followed from the discharge day to the third month after being discharged, was carried out in order to compare the costs and effectiveness of home care with the community-based nursing homes for stroke patients with different physical function disabilities in terms of ADL scores and their families. The ADL scores of the patients with severe physical function disability did not improve with or without long-term care; however, the patients with moderate physical function disability were significantly improved at the end of the third month, even without interventions from long-term care. The family costs of the patients in nursing homes were substantially lower than the costs for the patients who stayed at home, and the relationship of the family costs of the patients cared for in their own homes was proportional to the patients' physical function status. The labour input from family caregiving accounted for at least 60% of the total family costs of the patients who stayed at home, and the paid for long-term care services accounted for at least 60% of total family costs when the patients stayed in nursing homes. The multiple linear regression demonstrated that the degree of caregiving from families was a predictor of the amount of the costs families incurred for patients with severe physical function disability; as a result the ADL scored on discharge significantly influenced the average total family costs for the patients cared for in their own homes.

Activities of Daily Living↗

PubMed1997

Factors determining family caregiver's satisfaction with home care in the Taipei metropolitan area.

BACKGROUND: Among all types of long-term care, many studies have shown that home care is preferable. The increasing growth of an aging population with a predictable increase in chronic illnesses emphasizes the need to re-evaluate the current long-term care system. Because long-term care requires family members to participate as caregivers, there are resulting emotional, physical, and financial burdens, while to interacting with patients who suffer severe functional impairment. As these burdens exacerbate through time, family caregivers often seek assistance from home-care services. Evaluating the quality of home care provides an opportunity to adjust future planning and to envision a more ideal and effective home care plan in the Taipei metropolitan area. METHODS: This research was designed to evaluate the quality of home care by examining family caregivers' satisfaction with home-care services they render. Nineteen attributes of home-care services are cited in this study. The degree of satisfaction with each attribute of services was measured, using the Likert method of five response alternatives from "does not need to be improved at all" to "needs to be improved completely", coding from 5 to 1. The degree of general satisfaction with home care was reflected by averaging respondents' replies across 19 attributes. RESULTS: More than 91.0% of the family caregivers believed that respect from, consideration of, concern for questions by and acceptance of suggestions from home-care workers did not need any improvement. In contrast, at least two-thirds of the family caregivers felt the speedy provision of services in an emergency and the degree of ease of contact with home-care workers by telephone were acceptable only to some degree. For general satisfaction, 79.3% of the family caregivers scored in the range of 4.00-5.00 which indicated a need for mile improvement in services. The number of attributes desired which were in fact received was a significant determinant of general satisfaction with home-care services provided. Family caregivers who were credited with at least 14 attributes tended to be more satisfied with home-care services than the respondents who received fewer than 14. CONCLUSIONS: Overall, subjects receiving home-care services were generally satisfied. However, they were less satisfied with the ease of contacting home care workers by telephone and the speed of receiving needed services in an emergency. The more desired attributes of home care received reflected higher satisfaction with home-care services.

Adult↗

PubMed1997

The effectiveness of systematic stroke care.

A coordinated, multidisciplinary approach had been applied to enhance the effectiveness of stroke care with varying enthusiasm; however, the effectiveness of this kind of stroke treatment model was noted in many studies. This study was designed to measure the effectiveness of systematic stroke management on the physical-functional outcome in terms of Activities of Daily Living (ADLs) scores. The higher the ADLs score, the higher the degree of physical disability, i.e., the higher the degree of dependence. Eighty-six stroke patients from the Department of Neurology in a medical center, and 88 stroke patients from the Department of Medicine in a local hospital were followed from the admission day to the discharged date. The effectiveness of stroke care in each hospital was measured by the comparisons between ADLs scores at discharge and ADLs scores at admission. Two-sample tests show that demographic characteristics, length of stay, average time elapsed since the occurrent stroke, number of families in caregiving, and ADLs scores at admission and at discharge did not differ much between these two groups. The improved ADLs scores for stroke patients treated in the Department of Neurology of the medical center were changed from the 14.1 +/- 4.9 at admission to 12.1 +/- 5.2 at discharge, and the changes of ADLs scores for patients treated in the Department of Medicine of the regional hospital was from 12.8 +/- 5.1 to 12.3 +/- 5.5 according to the degree of improvement. The significant finding was that the degree of improvement of ADLs scores for CVA patients from the medical center was significant (Wilcoxon Matched-Pairs Signed-Ranks Test, Z = -2.8, p < 0.01). Moreover, the degree of improvement of ADLs scores strongly differed between these two groups (Repeated measures of two-way ANOVA, F = 6.0, p < 0.05). The information presented here informs us that degree of physical-functional status of stroke patients should be improved because of the systematic stroke management.

Activities of Daily Living↗

PubMed1996

Quantitative determination of butorphanol and its metabolites in human plasma by gas chromatography-electron capture negative-ion chemical ionization mass spectrometry.

Two separate analytical methods have been developed for the determination of butorphanol and its metabolites in human plasma. One method is specific for butorphanol (I) while the other determines the metabolites, hydroxybutorphanol (II) and norbutorphanol (III). Both procedures incorporate solid-phase extraction, chemical derivatization and separation, and detection using gas chromatography-electron-capture negative-ion chemical ionization mass spectrometry (GC-ECNCI-MS). Both methods use the cyclopropyl analog of I (BC-2605, IV) as the internal standard and the procedures for extraction of the analytes from plasma are identical. However, following extraction, either the pentafluorobenzoyl ester of I or the tris and bis-trifluoroacetyl esters of II and III, respectively, were prepared. The derivatives were analyzed by GC-ECNCI-MS with selected-ion monitoring of the molecular ions. The standard curves were linear over the concentration ranges of 20-2000, 20-1000 and 50-1000 pg/ml for I, II and III, respectively. All standard curves from the assay validation had r2 values of > or = 0.994, 0.991 and 0.985 for I, II and III, respectively. For all three compounds, the intra- and inter-assay precisions (C.V.) and inter-assay accuracy (deviation from nominal) were within 12% for plasma quality control samples. All derivatives were stable in the reconstitution solvent for at least 24 h. The assays are being used for the determination of plasma concentrations of I, II and III in humans following repeated administration of nasal spray.

Area Under Curve↗

PubMed1996

Vascular dementia of Binswanger's type: clinical, neuroradiological and 99mTc-HMPAO SPET study.

In 24 patients with vascular dementia of Binswanger's type (VDBT) and 14 age-matched neurologically normal volunteers, we investigated the relationship between clinical features, white matter lesions (leuco-araiosis) and cerebral atrophy on computed tomographic (CT) scan, and regional cerebral blood flow. All subjects underwent the Mini-Mental State Examination of Taiwan, version 1 (MMSE-T1), for assessing the severity of cognitive impairment. The patients were subdivided into two groups, one with mild to moderate (group I, MMSE-T1 scores: 11-24, n=11), and the other with severe dementia (group II, MMSE-T1 scores: below 10, n=13). White matter degeneration was evaluated with densitometric methods. Loss of brain parenchyma was estimated with seven linear measurements (Evan's ratio, third ventricle ratio, width of temporal horn tip, anterior-posterior length of temporal horn, anterior-posterior length of Sylvian fissure and width of frontal interhemispheric fissure) by CT scans. Regional cerebral blood flow was determined with technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET). In neuroimaging studies, subcortical leuco-araiosis was localized at the frontal region in group I patients and scattered diffusely in group II patients. 99mTc-HMPAO SPET analysis revealed reduction of regional cerebral blood flow in the frontal lobe in group I patients and widespread reduction of regional cerebral blood flow in group II patients. A correlation between frontal leuco-araiosis and perfusion defect of the frontal pole was demonstrated in group I patients, showing findings typical of subcortical dementia. There was no difference in frontal atrophic measurements between group I patients and controls. Ratios of volumes of lost brain parenchyma and leuco-araiosis were significantly higher in group II patients than in the age-matched controls, corresponding to a diffuse cerebral perfusion defect. These results suggest that patients with VDBT have early frontal lobe involvement with posterior progression. Patients with mild VDBT are more likely to show reduction of frontal cerebral blood flow and leuco-araiosis, while those with severe VDBT are more likely to have diffuse leuco-araiosis, cerebral hypoperfusion and brain atrophy.

Aged↗

PubMed1996

Panencephalitic Creutzfeldt-Jakob disease. Unusual presentation of magnetic resonance imaging and proton magnetic resonance spectroscopy.

We present serial magnetic resonance imaging (MRI) scans on a biopsy-verified case of Creutzfeldt-Jakob disease (CJD). The initial MRI scan demonstrated increased T2 signal-intensity within the basal ganglia and thalami. Subsequent MRI scans demonstrated a thin cortex, increased T2 signals diffusely within the white matter including U-fibers, and hypointense T2 signals within the basal ganglia, and thalami. Proton magnetic resonance spectroscopy (1H-MRS) study showed an absence of creatine, choline and N-acetylaspartate signals. By these characteristic findings, serial MRI and MRS studies may be helpful in differentiating CJD from other dementing illnesses.

Biopsy↗