Biomedical subjects

W H Chang

Publications and source records attributed to W H Chang.

At least 19 recordsLinked to original sources

PubMed1992

Splanchnic uptake of haloperidol and release of reduced haloperidol in vivo in the guinea pig.

Splanchnic uptake of haloperidol (HAL) and release of reduced haloperidol (RHAL) were studied in vivo in guinea pigs. Anesthetized animals with implanted cannulae in the aorta, the hepatic vein and the inferior vena cava were infused intravenously with HAL at a rate of 9.6 micrograms/min/animal for 90 min. Plasma HAL and RHAL in samples taken from the arterial and hepatic venous cannulae were measured by HPLC with an electrochemical detector. Contamination of the hepatic venous samples by blood from the inferior vena cava was ruled out by the validation method of tritiated water washout [Huang MT, J Appl Physiol 71: 359-364, 1991]. HAL concentrations plateaued at 70-80 ng/mL in the aorta and 5-7 ng/mL in the hepatic vein during the final 30 min of infusion. Splanchnic extraction of HAL was 91%. Hepatic blood flow was estimated to be 1.95 +/- 0.40 (SD) mL/min/g. If assuming that splanchnic uptake of HAL took place in the liver, a rate of uptake of HAL in the liver of 79.2 +/- 18.6 (SD) ng/min/g could be calculated by the Fick principle. The uptake in the whole liver accounted for 14% of the rate of HAL infusion into the animal. Plasma RHAL in the aorta, 6.4 +/- 6.6 (SD) ng/mL at 60 min and 9.4 +/- 4.6 (SD) ng/mL at the end of HAL infusion, was about 10-12-fold less than aortic HAL. The concentrations of RHAL in the hepatic vein were not significantly different from those in the aorta, indicating that splanchnic tissues including the liver are not responsible for plasma RHAL secretion. The highly efficient uptake of HAL as well as the ketone reductases found previously in vitro in liver microsomes of guinea pigs were probably involved only in biliary excretion of HAL.

Animals↗

PubMed1992

Pharmacokinetics of haloperidol and reduced haloperidol in Chinese schizophrenic patients after intravenous and oral administration of haloperidol.

The pharmacokinetics of haloperidol were studied in eight Chinese schizophrenic patients after intravenous administration and in six of the patients who also received oral haloperidol. After intravenous dosing, haloperidol disposition was best characterized by a three compartment model. The mean elimination half-life of 54.8 h determined by model dependent analysis was similar to the mean elimination half-life of 59.9 h determined by model independent analysis. The mean plasma clearance was 21.71/h and the mean volume of distribution during the distribution phase was 1754.3 1. After oral dosing, bioavailability of haloperidol was 35 +/- 8%, suggesting extensive first pass metabolism. Determination of reduced haloperidol concentration confirmed a previous finding of significant variability in haloperidol reductive capacity in individual patients. Comparison of area under the plasma concentration-time curve of reduced haloperidol after intravenous and oral administration of haloperidol suggests that reduction of haloperidol may only account for a small portion of first pass metabolism of haloperidol. However, conversion of reduced haloperidol back to haloperidol necessitates the monitoring of both haloperidol and reduced haloperidol concentrations in clinical practice.

Administration, Oral↗

PubMed1992

Reduced haloperidol: a factor in determining the therapeutic benefit of haloperidol treatment?

One of the metabolic pathways of haloperidol (HAL) is the reduction of the molecule at the benzylic ketone to form an alcohol metabolite, known as reduced HAL (RHAL). The basic and clinical pharmacology of RHAL is the subject of this review. The investigation of RHAL in biological samples has been suggested to be important, as the reduced metabolite can be reconverted back to the parent drug and is shown to be 20-50% as potent as HAL in some in vivo neuroleptic tests. Nevertheless, the metabolic reduction/oxidation cycle of the drug is unbalanced. The interconversion process largely favours the reduction of HAL to RHAL but not vice versa. The RHAL/HAL ratios are dose and time dependent. The higher the dose or the longer the duration of treatment, the greater the ratio. The results concerning relationship between plasma RHAL level or RHAL/HAL ratio and clinical response are inconsistent, yet interesting. Some studies in schizophrenic patients have suggested a diminished therapeutic response to HAL when elevated plasma RHAL concentrations or RHAL/HAL ratios are presented. However, this finding has not been replicated by other investigations. Possible interference by RHAL with HAL at dopamine receptors thus reducing the effectiveness of HAL treatment has been suggested by some authors. Measurements of RHAL as well as HAL plasma concentrations for evaluating drug level-clinical response might be necessary in psychiatric patients.

Animals↗

PubMed1992

Comparison of haloperidol and reduced haloperidol plasma levels in four different ethnic populations.

1. Plasma haloperidol and reduced haloperidol concentration were measured in four ethnic populations. 2. Plasma samples were obtained under steady-state conditions and obtained 10-12 hours post bedtime dose and prior to the morning dose. 3. Haloperidol and reduced haloperidol plasma levels were assayed by radioimmunoassay and liquid chromatography. 4. A wide interpatient variability between haloperidol dose and plasma concentration was observed for each ethnic group. 5. The Chinese group differed from the other ethnic populations. 6. A nonlinear relationship was observed between haloperidol and reduced haloperidol plasma levels in each ethnic group. Further, the relationship of haloperidol to reduced haloperidol plasma levels differed for each ethnic group. These results suggest that various ethnic groups could metabolize haloperidol and reduced haloperidol differently.

Black or African American↗

PubMed1992

Preliminary studies of duration and intensity of ultrasonic treatments on fracture repair.

Bone formation of fractured fibulae stimulated by ultrasound was evaluated with roentgenography and fluorochromes labelling. The fibulae of male New Zealand rabbits were fractured to create a 3 mm-gap. Ultrasounds at 0.5 or 1.0 W/cm2 were applied for various durations, 5, 15, and 25 min/day for 4 weeks. Ultrasonic treatments at 0.5 W/cm2, 1.5 MHz significantly accelerated bone formation at the fracture site for all durations, whereas the higher intensity at 1.0 W/cm2 suppressed the bone formation of the treated fractured fibula. Ultrasounds at 0.5 W/cm2 were stimulatory to fracture repair, if given for 15 min/day, and were recommended for future clinical trials. However, ultrasounds at the intensity of 1.0 W/cm2 were deleterious to the treated fracture and not recommended for clinical trials.

Animals↗

PubMed1992

Ultrasonic effect on fracture repair and prostaglandin E2 production.

Ultrasound has been recently recognized of its potential in promoting fracture healing. However, its effects on bone healing remain unclarified. The present study was initiated to compare the effects of frequency on fracture healing and the possible role of endogenous prostaglandin E2 in fracture healing stimulated by ultrasound. Histologic evaluation of callus formation with labelled fluorochromes indicated that the use of ultrasound at 1.5 MHz was most effective in accelerating bone healing. In addition, at this frequency, the endogenous PGE2 level was significantly elevated, which paralleled the accelerated bone healing. It is suggested that bone healing stimulated by ultrasound may be mediated via the production of PGE2.

Animals↗

PubMed1992

Interindividual variabilities in haloperidol interconversion and the reduced haloperidol/haloperidol ratio.

Metabolism of haloperidol in humans includes N-dealkylation to inactive metabolites and reduction to reduced haloperidol; reduced haloperidol is also oxidized back to haloperidol. A single 0.5 mg/kg (0.00133 mmol/kg) oral dose of haloperidol and reduced haloperidol was administered to seven Chinese schizophrenics in a randomized crossover manner separated by a 2-week interval. The clearance values for the different metabolic pathways of haloperidol and reduced haloperidol were determined. There were differences up to 10-fold in both oxidation and reduction capacities. There were also interindividual variabilities in the elimination of reduced haloperidol (0.37 +/- 0.20 L/hr/kg) and the N-dealkylation pathway (0.74 +/- 0.36 L/hr/kg). Four weeks after the single-dose study, the same patients also received haloperidol (10 mg) twice daily for 4 weeks. The reduced haloperidol to haloperidol concentration ratio (0.40 +/- 0.16) after the 4-week therapy is related to individual variabilities in the interconversion process and the N-dealkylation pathway of haloperidol.

Adult↗

PubMed1991

Identification of a stretch-activated monovalent cation channel from teleost urinary bladder cells.

The urinary bladder of euryhaline teleost is an important osmoregulatory organ which absorbs Na+, Cl-, and water from urine. Using patch clamp technique, single stretch-activated channels, which were permeable to K+ and Na+ (PNa/PK approximately 0.75) and had conductances of 55 and 116 pS, were studied. In excised, inside-out patches which were voltage-clamped in the physiological range of membrane potential, the single-channel open probability (Po) was low (approximately 0.02), and increased to a maximum of 0.9 with applied pipette suction. Single-channel conductance also increased with suction. The channels showed adaptation to applied suction and relaxed to a steady-state activity about 20 seconds after application of suction. The Po increased up to 0.9 with strong membrane depolarization (Vm = 0 to +80 mV); however, there was little dependence of Po on membrane potential in the physiological range. The kinetic data suggest that there is one conducting state and at least two non-conducting states of the channel. The open-time constant increased with suction but remained unchanged with membrane potential (Vm = -70 to +60 mV). The mean closed-time of the channel decreased with suction and membrane depolarization. These results demonstrate the presence of a non-selective monovalent cation channel which may be involved in cell volume regulation in the goby urinary bladder. Additionally, this channel may function as an enhancer of Na+ influx and K+ efflux across the bladder cell as part of transepithelial ion transport if it is located in apical membrane.

Animals↗

PubMed1991

Dose-dependent reduced haloperidol/haloperidol ratios in schizophrenic patients.

Plasma haloperidol (HAL) and reduced HAL (RHAL) concentrations were measured in 113 Chinese schizophrenic patients. Daily doses of HAL ranged from 8 to 65 mg. Samples were obtained under steady-state conditions and drawn 10-12 hours after the bedtime dose and before the morning dose. In all, 313 blood samples were collected. Multiple samples were obtained at the same doses in 63 patients and at two or three different doses in 31 patients. HAL and RHAL concentrations were assayed by high performance liquid chromatography. Interpatient variation in plasma HAL levels at a given dosage was up to sixfold. However, there was a high positive correlation between plasma levels and daily dosages with the equation of HAL plasma level (ng/ml) = 0.88 x dosage (mg/day) -0.56 or 46.0 x dosage (mg/day/kg) + 0.28. The expected values are about 15-55% higher than those obtained from non-Chinese patients as reported in the literature. The RHAL/HAL ratios were dose-dependent. The greater the dose used, the higher the ratio. An upper therapeutic limit of plasma HAL level is suggested to be 25 ng/ml, which can be achieved at dosages about 30 mg/day in most Chinese patients. Based upon the dose-dependent increase in RHAL/HAL ratios, the importance of RHAL in determining the therapeutic benefit of HAL treatment is discussed.

Adolescent↗

PubMed1991

A case of post-traumatic coronary occlusion.

Several cases of transmural myocardial infarction and ventricular aneurysm caused by a blunt trauma of the chest have been reported. Nevertheless, the cases documented with coronary and ventricular angiography are very few. There has always been a debate over the etiological mechanism of such lesions. Since in some cases there was no evidence of coronary lesions, it was postulated that they were produced by direct myocardial contusion, but in other instances the evidence of coronary occlusion was angiographically and pathologically proved. We experienced a case of acute myocardial infarction with ventricular aneurysm secondary to nonpenetrating chest trauma by an umbrella tip and wish to report this unusual case, along with a review of the literature.

Adult↗

PubMed1991

Ethnic comparison of haloperidol and reduced haloperidol plasma levels: Taiwan Chinese versus American non-Chinese.

Steady-state haloperidol (HAL) and reduced HAL (RHAL) plasma levels were measured in Chinese and non-Chinese schizophrenic patients. The patients (n = 38) were matched according to age (+/- 1 yr) and by HAL dose. In general, Chinese patients had higher mean plasma HAL levels and lower RHAL/HAL ratios compared to non-Chinese patients (23.6 +/- 14.9 ng/ml versus 17.1 +/- 10.1 ng/ml, p less than 0.05; 0.52 +/- 0.44 versus 0.82 +/- 0.62, p less than 0.05). Six groups were formed according to HAL dose (number per group): 10 mg/day (6); 20 (11); 30 (11); 40 (4); 50 (3); and 60 (3). No significant differences were found in age, weight and dose/weight. In each dose group, HAL plasma levels were generally higher in the Chinese patients than in the non-Chinese patients, though significance was only detected in the 30 mg group (26.1 +/- 7.0 ng/ml versus 18.5 +/- 5.1 ng/ml, p = 0.035) and a slight trend in the 40 mg group (36.0 +/- 15.0 ng/ml versus 23.5 +/- 10.4 ng/ml, p = 0.074). RHAL/HAL ratios were generally lower in the Chinese patients than in the non-Chinese patients, with a strong trend toward the significance level in the 20 mg and 30 mg groups (0.22 +/- 0.13 versus 0.58 +/- 0.57, p = 0.066 and 0.43 +/- 0.26 versus 0.71 +/- 0.34, p = 0.062). This study further suggests the possibility of different metabolic rates between Chinese and non-Chinese patients. Possible differences in the enzyme systems which relate to the metabolism of HAL and RHAL between Chinese and non-Chinese populations are discussed.

Adult↗

PubMed1991

Enhancement of fracture healing by specific pulsed capacitively-coupled electric field stimulation.

The histologic procedure technique was used to evaluate the bone fracture healing rate of manually fractured fibulae after they were submitted to several different types of capacitively-coupled electric field stimulation, classified depending on the parameters of peak-to-peak voltage, frequency and duration. Using a completely randomized design, 30 New Zealand male rabbits were divided into six different groups: a control group, a 60 kHz and 220 mVp-p sine wave group as proposed by Brighton in 1985, and four special parameters of pulse wave groups. After comparing these different types of electrical stimulation, the group with the parameters of a pulse train repetition frequency of 15 Hz, a pulse frequency of 10 kHz and 5 V peak-to-peak intensity experienced the same enhancement of bone fracture healing as the group with the parameters suggested by Brighton in 1985.

Animals↗

PubMed1991

Additive effects of prostaglandin E2 and pulsed electromagnetic fields on fracture healing.

Bone formation of fractured fibulae stimulated by pulsed electromagnetic fields (PEMF), PGE2, and combination of both was assessed with roentgenography and fluorescent labelling compounds, tetracycline, xylenol orange, and calcein. A total of 72 male New Zealand rabbits was osteotomized by creating a 1 mm-gap at fibulae and randomly divided into 8 groups: one control, one treated with PEMF, three treated with PGE2 of various dosages, and three treated with combined treatments of PEMF and PGE2 of specified dosages. PEMF had positive effects on bone formation. Exogenous PGE2 mimicked the effect of PEMF on linear bone growth. The effect of PGE2 on bone formation or bone remodelling was dose-related (5, 15, 50 micrograms/kg), with 5 micrograms/kg body weight as the optimal dosage in this study. Combination of PEMF and PGE2 exhibited a trend of additive effect on bone formation, especially at 15 micrograms/kg of PGE2. It is hypothesized that PEMF may exert its action on bone healing by increasing the endogenous PGE2. We therefore concluded that external stimulation such as PEMF and PGE2 was beneficial and stimulatory towards bone formation and healing in our animal model. However, the effects were somehow specific in electrical waveforms and dosage. Similar to PEMF, PGE2, therefore, may be a potential agent in promoting bone formation in the clinical treatments of fractures or perhaps non-union.

Animals↗

PubMed1991

Ultrasound can affect bone healing both locally and systemically.

Bone formation of fractured fibulae stimulated by ultrasound was evaluated with roentgenography and fluorochromes labelling. The fibulae of male New Zealand rabbits were fractured to create a 3 mm-gap. A pilot study was performed to determine the treatment interval for fracture healing of the fibula. Ultrasonic treatment at 1.0 W/cm2, 1.5 MHz for 15 min/day significantly accelerated bone formation at the fracture site of the un-treated fibula, but suppressed the bone formation of the directly treated fractured fibula. Subsequent treatments with these specificities showed that ultrasonic treatment on the unoperated fibula also significantly accelerated the bone formation of the contralateral fractured fibula. It was suggested that locally applied ultrasound at the intensity of 1.0 W/cm2 was deleterious to the treated fracture or intact fibula, but simultaneously would stimulate bone formation of the contralateral fibula.

Animals↗

PubMed1991

Interconversions between haloperidol and reduced haloperidol in schizophrenic patients and guinea pigs: a steady-state study.

Plasma concentrations of haloperidol (HAL) and reduced haloperidol (RHAL) were measured in 8 schizophrenic patients, neuroleptic-free for at least 4 weeks, after repeated oral administrations of 10 mg HAL and RHAL. Each agent was given for 10 days with a 2-week washout period between the two compounds. HAL and RHAL were interconverted in all subjects. Plasma RHAL/HAL ratios at steady state during HAL treatment were significantly greater than the HAL/RHAL ratios after repeated reduced HAL administration (0.51 +/- 0.12 vs. 0.16 +/- 0.04 SD, p less than 0.0005). This result suggests that the interconversions between HAL and RHAL are apparently not equivalent in humans. A negative correlation was found between RHAL/HAL ratios after HAL administrations and HAL/RHAL ratios after RHAL administrations (r = -0.82, p less than 0.05). Repeated injections of HAL or RHAL at low (0.1 mg/kg) or high (1.0 mg/kg) doses were conducted in guinea pigs. Drug concentrations in striatum and plasma were measured. Both RHAL/HAL ratios after HAL injections and HAL/RHAL ratios after RHAL injections were dose- and time-dependent. High doses and repeated injections produced greater RHAL/HAL ratios after HAL and smaller HAL/RHAL ratios after RHAL than those observed with low doses and single injections, respectively. Compared with the results obtained from schizophrenic patients, the conversion from HAL to RHAL in guinea pigs was greater than that in humans, but the back conversions appeared to be similar between the guinea pigs and humans. Based upon the dose-dependent increase in RHAL/HAL ratios, a hypothesis of the therapeutic window effect for HAL treatment is proposed.

Adult↗

PubMed1990

Plasma catecholamine metabolites in schizophrenics: evidence for the two-subtype concept.

Plasma homovanillic acid (pHVA) and plasma methoxyhydroxyphenyl glycol (pMHPG), as well as plasma haloperidol, were measured in 33 schizophrenic patients before and during 6 weeks of haloperidol treatment. Good responders had higher baseline pHVA values compared with poor responders (17.4 +/- 8.8 ng/ml, n = 22 versus 11.4 +/- 5.0 ng/ml, n = 11, p less than 0.05). A higher than 15 ng/ml pretreatment pHVA level was associated with a more consistent clinical response to the subsequent treatment. Differential pHVA changes during treatment were also found between good and poor responders. Within the good responder group, a significant decline in pHVA over time was found. By contrast, pHVA showed a transient increase in the poor responder group. Plasma MHPG changes showed a similar pattern during treatment in good responders, although no significant differences in baseline values were found between the good (n = 13) and poor (n = 9) responders, and pMHPG showed no change during treatment in poor responders. Significant correlations between baseline pHVA and pMHPG values were found in 22 patients. Good responders and poor responders did not differ significantly in terms of age, duration of illness, severity of presenting symptoms, haloperidol dose, or plasma drug concentration. Two hypothetical subtypes of schizophrenia and both dopamine and norepinephrine systems involved in schizophrenic psychopathology are proposed.

Adult↗

PubMed1990

Reversible metabolism of haloperidol and reduced haloperidol in Chinese schizophrenic patients.

Haloperidol disposition has been associated with reversible metabolism: it is reversibly reduced to its metabolite, reduced haloperidol, which has less pharmacologic activity than the parent compound. To characterize the interconversion process, six healthy male schizophrenics were administered a single dose of 10 mg haloperidol or reduced haloperidol in a randomized crossover manner. Using a general pharmacokinetic model for the interconversion process, the clearances of haloperidol and reduced haloperidol are 1.15 +/- 0.32 l/h/kg and 0.76 +/- 54 l/h/kg, respectively. These clearances are similar to that obtained by the usual mammillary model analysis. With a single 10 mg dose administration of either drug, about 23% of the biotransformation of haloperidol involves the reduction pathway. Back conversion from the reduced metabolite to the parent drug through oxidation contributes even less to the total biotransformation of reduced haloperidol. This action of interconversion or saturation under chronic drug administration is unknown. Reversible metabolism of haloperidol could partially account for the wide therapeutic range for haloperidol as reported in the literature.

Adult↗

PubMed1990

Serological classification by monoclonal antibodies of Rickettsia tsutsugamushi isolated in Korea.

Antigenic types of 113 strains of Rickettsia tsutsugamushi isolated from Korean patients were analyzed by using murine polyclonal and monoclonal antibodies. The isolates can be classified in six groups according to their reaction to a panel of monoclonal antibodies. Nine isolates of group I were identified as the Gilliam serotype, and 13 isolates of groups II and III were identified as the Karp serotype. There were two groups that were considered to be a mixture of groups I and II or groups I and III, respectively. The remaining 88 strains of group IV had a unique antigenic determinant that was not present in the prototype strains (Karp, Kato, Gilliam), in addition to sharing common antigens with the prototype strains. Therefore these strains, which are more prevalent in Korea, seem to belong to a new serotype closely related to the Karp serotype.

Animals↗