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Biomedical subjects

W H Chang

Publications and source records attributed to W H Chang.

At least 91 records · Page 5Linked to original sources

Haloperidol and reduced haloperidol plasma concentrations after a loading dose regimen with haloperidol decanoate.

1. Haloperidol and reduced haloperidol plasma levels were measured in schizophrenic patients who received both oral (10 mg, N=16 and 20 mg, N=4) and depot haloperidol treatment 2. Patients were of Asian ethnicity and were safely and effectively converted from oral to depot therapy using a loading dose regimen using a 100 mg weekly injection interval for 4 weeks, biweekly for one month and then monthly. 3. Significant correlations were found for plasma haloperidol and reduced haloperidol levels and reduced haloperidol/haloperidol ratios between oral and depot therapy in these non-smoking patients. 4. A loading dose regimen is needed due to the long elimination half-life of decanoate of 26 days otherwise steady-state condition will not occur until 34 months of therapy. 5. Patients were maintained on monthly depot treatment for 40 weeks after the loading dose regimen and only one patient relapsed during treatment despite dosage increases. 6. The formation of reduced haloperidol remained consistent for oral and depot haloperidol treatment.

Adult↗

Monitoring of plasma clozapine levels and its metabolites in refractory schizophrenic patients.

Plasma concentrations of clozapine and its metabolites desmethylclozapine and clozapine N-oxide were measured in 61 patients with refractory schizophrenia. Before the initiation of clozapine, each patient was given haloperidol (HL) up to 60 mg/day for at least 4 weeks without improvement. Patients were then given a fixed dose of clozapine 400 mg/day. Patients were assessed with the Brief Psychiatric Rating Scale (BPRS) at baseline before HL therapy, at the end of HL at 6 weeks, before clozapine, and after 6 weeks of clozapine therapy. Clozapine and its metabolites were measured by high-performance liquid chromatography with ultraviolet detection. The mean plasma concentrations of clozapine, desmethylclozapine, and clozapine N-oxide were 598 +/- 314, 281 +/- 140, and 90 +/- 29 ng/ml, respectively. The mean decrease in the total BPRS scores from baseline clozapine to the 6-week treatment period was 11 +/- 4. Clinical improvement was noted to occur in most patients with clozapine plasma levels > 300 ng/ml. Improvement diminished in patients with clozapine plasma levels > 700 ng/ml. The most common adverse effects were sedation and hypersalivation. Significant correlations between plasma clozapine concentrations and adverse side effects were not found.

Adult↗

Genetic analysis of Borrelia burgdorferi sensu lato in Korea using genomic hybridization and 16S rRNA gene sequence determination.

Nine Borrelia burgdorferi sensu lato isolated in Korea were subjected to genomic hybridization using 16S rRNA gene probe and specific restriction patterns (HindIII and EcoRV) led these nine Borrelia into five subtypes. The evolutionary relationships of the five isolates corresponding to five RFLP groups were measured through the sequence determination of 16S rRNA gene and phylogenetic analysis. The isolates 935T (group I), 934U and 17Y (Group IIa, IIb) were well clustered with B. garinii and B. afzelii. 5MT and 9MT strains (Group IIIa and Group IIIb) formed a common branch shared with B. afzelii cluster although the evolutionary distance was rather long. So, most of B. burgdorferi sensu lato in Korea was B. afzelii or B. afzelii-related group and some minor group such as B. garinii also existed.

Borrelia burgdorferi Group↗

Expression and purification of the crystalline surface layer protein of Rickettsia typhi.

The crystalline surface layer (S-layer) protein (SLP) of Rickettsia typhi is known as the protective antigen against murine typhus. We previously reported a cloning and sequence analysis of the SLP gene of R. typhi (slpT) and showed that the open reading frame of this gene encodes both the SLP and a 32-kDa protein. To express only the SLP from this gene, the putative signal sequence and the 32-kDa protein portion were removed from the slpT. This protein was expressed in Escherichia coli as a fusion protein, consisting of the SLP and maltose binding protein. The recombinant protein reacted strongly with polyclonal antiserum of a patient with murine typhus.

ATP-Binding Cassette Transporters↗

Design and assessment of an adaptive intermittent cervical traction modality with EMG biofeedback.

An intermittent cervical traction modality with closed-loop traction force control based on EMG biofeedback was developed and used for clinical study. This system consists of a EMG scanner, on-line self-adjusted traction force controller, audio/video alarm system, real time therapeutic status display, computer interface hardware, and control software. Twenty-four subjects with diagnosed cervical radiculopathy and muscle spasm symptom who were randomly divided into two groups served as subjects in this study. The control and experimental groups were treated with conventional open loop and new EMG biofeedback closed loop traction control protocols respectively. The results of this study indicate that the average reductions in paraspinal EMG signal during traction after 7 weeks treatment for experimental and control groups were 71 and 50 percent, respectively (p < 0.001). These results not only support the clinical use of intermittent, sitting traction to produce cervical paraspinal muscle relaxation, but also revealed that the average myoelectric activity of cervical paraspinal muscle during traction was reduced as traction force increased over the 7-week duration of traction treatment. Through EMG biofeedback traction force control, muscle injury, neck soreness, or pain after traction may be avoided.

Adult↗

Plasma haloperidol and reduced haloperidol concentrations in a geriatric population.

Haloperidol (HL) and reduced haloperidol (RH) plasma concentrations were measured in geriatric patients (n = 45) and schizophrenic patients (n = 8). In the elderly patients, HL doses were 1-4 mg/day while only 2 mg/day was used in the schizophrenics. At HL 2 mg/day dose in both age groups, mean plasma HL levels were approximately twice as high in the elderly patients compared to the schizophrenics (1.39 +/- 0.82 vs. 0.56 +/- 0.23 ng/ml, p < 0.02). RH plasma concentrations were almost 5 times greater in the elderly patients (0.54 +/- 0.35 vs. 0.09 +/- 0.05 ng/ml, p < 0.0001). These results suggest that HL plasma concentrations in the elderly are greater than in adult schizophrenic patients treated with similar HL doses.

Adult↗

Transmission of scrub typhus by needlestick from a patient receiving pefloxacin.

A nurse experience a needlestick during the care of a patient with scrub typhus, treated with pefloxacin (400 mg twice daily) and cefazolin. Seven days after the needlestick, pain and erythematous swelling developed at the tip of her left fourth finger, the site of the needlestick. Fever and headache developed 10 days later, and her skin lesion became a small vesicle surrounded by a dark erythematous area. The diagnosis of scrub typhus was made by a rising indirect immunofluorescent antibody titre, and her illness was improved with doxycycline.

Adult↗

A practical loading dose method for converting schizophrenic patients from oral to depot haloperidol therapy.

BACKGROUND: Haloperidol decanoate is a long-acting depot antipsychotic agent used for the treatment of schizophrenic patients. The decanoate formulation was developed to treat schizophrenics who have a history of noncompliance with oral medication. Studies of techniques to convert from oral to depot therapy have not utilized the pharmacokinetics of the decanoate formulation. This study is a prospective evaluation for converting patients from oral to depot treatment. METHOD: Twenty-one patients meeting DSM-III-R criteria for schizophrenia participated in the study. Patients were treated with oral haloperidol for 6 weeks and then were switched to decanoate. Haloperidol decanoate 100 mg was administered on a weekly basis for the first 4 weeks. Afterward, injection intervals were increased to every 2 weeks and then to every 4 weeks. Plasma haloperidol concentrations were obtained prior to the next injection and assayed by HPLC with electrochemical detection. Patients were monitored by the psychiatrists and nursing staff for symptoms of clinical deterioration. RESULTS: All patients completed the conversion trial during the first 4 weeks without any problems or adverse side effects. By the third week, mean plasma haloperidol concentrations from the decanoate injections were comparable with those of the 10-mg oral haloperidol treatment (7.95 +/- 4.94 ng/mL vs. 7.79 +/- 4.79 ng/mL). Steady-state conditions for the decanoate therapy were achieved by the fourth week. CONCLUSION: These findings suggest that schizophrenic patients can be easily converted from oral to depot therapy without problems. Further studies with haloperidol decanoate and its conversion from oral treatment utilizing plasma concentrations are needed.

Administration, Oral↗

Disposition of remoxipride in Chinese schizophrenic patients.

The disposition of remoxipride was evaluated in 13 male chronic schizophrenic patients. A single 150 mg dose of remoxipride was administered and blood sampling performed over the following 48 hours. The mean (SD) oral clearance and half-life of remoxipride were 74.46 (25.9) ml/min and 5.46 (0.87) hours, respectively. The mean (SD) AUC for remoxipride was 25,320 (9,820) ng.h/ml. A wide interpatient variability was observed. Compared to Caucasian studies there were no significant differences in the disposition of remoxipride.

Adult↗

Ketone reductase activity and reduced haloperidol/haloperidol ratios in haloperidol-treated schizophrenic patients.

Twenty schizophrenic patients were treated with a fixed haloperidol (HL) dose of 20 mg/day for 4 weeks. The conversion of HL to its reduced metabolite (reduced haloperidol, RH) occurs via the ketone reductase enzyme. RH is also converted back to HL by the cytochrome P450 2D6 isozyme. Ketone reductase activity can be measured in red blood cells. Plasma HL and RH levels were assayed by high performance liquid chromatography. Blood samples were obtained at baseline and during weeks 2 and 4 of HL therapy. Seventeen of 20 patients had ketone reductase values < 3. A significant correlation between ketone reductase and RH/HL plasma ratios was observed at week 4 in these 17 patients. Patients with ketone reductase activity < 3 could represent a subgroup of patients that metabolize HL differently. The wide interpatient variability observed with HL and RH plasma levels in HL-treated patients could reflect differences in ketone reductase activity and the metabolic status of debrisoquin hydroxylase (cytochrome P450IID6) in psychiatric patients.

Adult↗

Intra- and interethnic variability in reduced haloperidol to haloperidol ratios.

Steady-state haloperidol and reduced haloperidol concentrations were measured in 250 schizophrenic patients from 4 ethnic groups: 39 Blacks, 66 Caucasians, 82 Chinese, and 63 Mexican Americans. The distribution of the reduced haloperidol to haloperidol concentration (RH/HL) ratios was bimodal in all ethnic groups, with the antimode determined by probit plot as 0.46, 0.51, 0.36, and 0.76, respectively. With these antimodes, the proportion of patients with low RH/HL ratios were 41%, 42%, 73%, and 57% in the four ethnic groups, respectively. Compared with the other three ethnic groups, in the Chinese patients the ratio was lower. The mean RH/HL ratio in the Chinese was 0.34 compared with 0.81 to 0.87 in the non-Chinese groups. In 53 patients who were treated with two or more haloperidol dosage regimens, steady-state haloperidol and reduced haloperidol drug concentrations obtained from the different regimens were positively correlated with the haloperidol dose (R = .79 and R = .62, respectively). Our data suggest not only the existence of a bimodal distribution in the RH/HL ratio, but also that the antimode separating the low and high ratio subgroups is different among the various ethnic groups.

Adult↗

Short-course doxycycline treatment versus conventional tetracycline therapy for scrub typhus: a multicenter randomized trial.

To assess the clinical efficacy of short-course doxycycline in the treatment of scrub typhus, we compared conventional 7-day tetracycline therapy with 3-day doxycycline therapy in 116 patients. Patients were randomized to receive either tetracycline (500 mg four times daily; n = 50) or doxycycline (100 mg twice daily; n = 66) and were followed for 4 weeks after the completion of treatment. The cure rate was 100% in the tetracycline group and 93.9% in the doxycycline group (P > .05). The two groups did not differ significantly in terms of the interval required for defervescence or for the alleviation of symptoms. There were no relapses in either group. These data suggest that 3-day doxycycline therapy is as effective as conventional 7-day tetracycline therapy for the cure of scrub typhus and the prevention of relapses.

Adult↗

Determination of human plasma biogenic amines and their metabolites using liquid chromatography with a dual-channel electrochemical detector.

BACKGROUND: Measurement of biogenic amines and their metabolites in plasma has been used for decades to explore the pathophysiology of neuropsychiatric disorders or to examine the mode of action of psychotropic medications. Many advantages of ultrafiltration and high-performance liquid chromatography (HPLC) in assaying human plasma content have been described in our previous study. METHODS: The present HPLC assay, applying a dual-channel electrochemical detector, provides an additional reliable measurement or confirmation of peaks by identifying each peak retention capacity factor and its current ratio in the dual-channel detector. Simultaneous measurements of plasma serotonin, catecholamines and their metabolites by ultrafiltration and microbore HPLC technique is applied to evaluate moclobemide and fluoxetine therapy in patients with major depression. RESULTS: This present HPLC method provides highly specific detection, free from interference by the large offscale peak of plasma ultrafiltrates. Isocratic separation of all analytes by a microbore column is achieved within 15 mins. The detection limit (signal-to-noise ratio = 3) of this method is about 0.2-0.5 pg per injection for all analytes. In addition, the required volume of plasma samples is only 100 microliters. CONCLUSIONS: This rapid, simple and sensitive method for the measurement of human plasma serotonin, catecholamines and their metabolites can be used as a clinical or biomedical research tool. Blood loss is minimal in the present assay, especially in repeated blood sampling for pharmacokinetic studies.

3,4-Dihydroxyphenylacetic Acid↗

Haloperidol plasma concentrations in Taiwanese psychiatric patients.

Haloperidol and reduced haloperidol are interconverted. The plasma concentrations of these two butyrophenones have been suggested to be important factors in determining the clinical effect of haloperidol treatment. The steady-state plasma concentrations of haloperidol and reduced haloperidol were measured in 322 Taiwanese schizophrenic patients using high performance liquid chromatography. The daily doses of haloperidol varied from 5 to 200 mg (mean +/- SD, 35.3 +/- 34.6 mg). There was a positive correlation between plasma concentrations and doses, following the equation: haloperidol concentration (ng/mL) = 0.88 x dose (mg/day)-1.66. However, the interpatient variation in haloperidol concentrations was up to ten-fold even in patients receiving the same dose (20 mg/day, n = 88). The expected values were about 10% to 50% higher than those reported in Caucasian patients. The plasma reduced haloperidol concentrations were significantly lower than, and correlated with, those of haloperidol in patients with haloperidol levels lower than 25 ng/mL. However, once haloperidol exceeded 25 ng/mL, reduced haloperidol levels rapidly elevated and appeared significantly higher than haloperidol levels. While haloperidol could reach its steady state in about 1 week, reduced haloperidol needed at least 4 weeks to do so. Haloperidol doses of less than 30 mg/day and plasma concentrations lower than 25 ng/mL are recommended for most Chinese patients.

Adult↗

Disposition of clozapine and desmethylclozapine in schizophrenic patients.

The disposition of the atypical clozapine and its desmethyl metabolite were evaluated in fourteen male chronic patients. A single 100 mg dose of clozapine was administered and blood sampling performed over the following 72 hours. The mean (SD) oral clearance and half-life of clozapine were 55.4 (29.7) L/hr and 13.7 (9.9) hours, respectively. The mean (SD) AUC for clozapine and desmethylclozapine was 2389.9 (1406) and 751.1 (622.9) ng.hr/mL, respectively. The elimination of the metabolite is rate limited by its formation from cloza-pine. A wide interpatient variability in clozapine and desmethylclozapine pharmacokinetics was observed.

Adult↗