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Biomedical subjects

W H Chang

Publications and source records attributed to W H Chang.

At least 109 records · Page 6Linked to original sources
PubMed1994

Plasma reduced haloperidol/haloperidol ratios in schizophrenic patients treated with high dosages of haloperidol.

Plasma haloperidol (HL) and reduced haloperidol (RH) levels were measured in 60 schizophrenic patients treated with high to very high HL doses of 40-200 mg/day. Plasma samples were obtained at steady-state conditions and 10-12 h after the evening dose and prior to the morning dose. RH/HL ratios were shown to be dose-dependent. In the lowest dose group of 40-45 mg/day, 77% of the patients had RH/HL ratios < 1.0. At the higher dose of 60-80 mg/day, these results were reversed as 79% of the patients had RH/HL ratios > 1.0. All patients with HL doses greater than 100 mg/day had RH/HL ratios > 1.0. All patients safely tolerated the high haloperidol dosages and only five patients had extrapyramidal side effects that were unresponsive to trihexyphenidyl. Therapeutic improvement was not observed in each patient. Based upon the dose-dependent increase in the RH/HL ratios in schizophrenic patients, the possible mechanism of a 'therapeutic' window for HL is discussed.

Adult↗
PubMed1994

Detection of leptospiral DNA by PCR.

An EcoRI fragment (1.2 kb) which is highly conserved among Leptospira interrogans isolated in Korea was cloned into pBluescript vector from L. interrogans serovar lai WH20. The EcoRI fragment was sequenced, and a pair of primers (LP1 and LP2) was designed for PCR assay. PCR amplification of target DNA obtained from cultured L. interrogans showed that 274 bp could be detected when as little as 100 fg of leptospiral genomic DNA was used in the reaction mixture. No amplification of DNA was detected from DNA of Leptospira biflexa serovars patoc and sau paulo, Borrelia burgdorferi, Staphylococcus aureus, Escherichia coli, and Salmonella typhimurium. Amplification of 274-bp target DNA could be detected in DNA samples purified from 500 microliters of blood collected from experimentally infected gerbils 2 days after infection, while antibodies to L. interrogans could be detected by the microscopic agglutination test 7 days after infection. The specificity and high sensitivity of the test provided valuable tools for the early diagnosis of leptospirosis.

Agglutination Tests↗
PubMed1994

Detection of Rickettsia tsutsugamushi in Experimentally infected mice by PCR.

We developed a rapid procedure for the detection of Rickettsia tsutsugamushi DNA by the PCR technique. The primer pair used for the PCR was designed from the DNA sequence of the gene encoding a 120-kDa antigen, which was proven to be group specific by immunoblot analysis with mouse hyperimmune sera against various rickettsial strains. This PCR method was able to detect up to 10 ag of plasmid DNA (pKT12). Specific PCR products were obtained with DNAs from R. tsutsugamushi Kato, Karp, Gilliam, TA716, TA1817, and Boryong, but not with DNAs from other rickettsiae, such as R. prowazekii, R. typhi, R. akari, and strain TT118. In a study with experimentally infected mice, the PCR method could detect rickettsial DNA from 2 days after inoculation (DAI), whereas serum antibody against R. tsutsugamushi could be detected from 6 to 8 DAI by an immunofluorescence test. Although clinical manifestations subsided after 14 DAI, rickettsial DNA in blood samples could be detected by PCR for up to 64 DAI. These results suggest that this PCR method can be applied to the early diagnosis of scrub typhus and can also be used to detect the residual rickettsiae after clinical symptoms subside.

Animals↗
PubMed1994

Reversible metabolism of drugs.

Many drugs undergo reversible metabolism. The basis of our understanding of this process is the reversible metabolism of prednisone (PD)-prednisolone (PL). The pharmacokinetics of reversible metabolism requires the use of four area under the curve values integrated into four equations for clearance (CL). Other variables, such as linear versus non-linear disposition, can play important roles in reversible metabolism. Of recent interest is the reversible metabolism of haloperidol which consists of an interconversion process between the parent drug haloperidol (HL) and its reduced metabolite (RH). However, the interconversion of HL-RH differs from the PD-PL model in that, whereas PD and PL are both active, RH is considered to be a therapeutically inactive, possibly toxic, metabolite. This article reviews the pharmacodynamic and pharmacokinetic properties of HL and RH and the possible clinical effects that can result from this reversible metabolism.

Animals↗
PubMed1993

Cloning and sequence analysis of the gene encoding the crystalline surface layer protein of Rickettsia typhi.

The nucleotide sequence of the gene (slpT) encoding the crystalline surface layer protein (SLP) of Rickettsia typhi was determined. The slpT gene consists of 4935 bp coding for a 1645-amino-acid (aa) protein containing a predicted signal peptide at the N terminus. The size of the predicted SLP exceeds the observed size (135 kDa) on SDS-PAGE. The N-terminal aa sequence of the 32-kDa protein of R. typhi reported by Hackstadt et al. [Infect. Immun. 60 (1992) 159-165] was found in the C-terminal portion of the deduced aa sequence, suggesting that the product of slpT is processed into the mature SLP and the 32-kDa protein.

Amino Acid Sequence↗
PubMed1993

Rapid and reliable high-performance liquid chromatographic method for analysing human plasma serotonin, 5-hydroxyindoleacetic acid, homovanillic acid and 3,4-dihydroxyphenylacetic acid.

The simultaneous measurement of homovanillic acid, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in human plasma by an ultrafiltration and microbore high-performance liquid chromatography-electrochemical detection technique is established. Conventional preparation of blood is very tedious and time-consuming, but isocratic separation of the analytes in plasma ultrafiltrates using a microbore column could be achieved within 10 min. Hence, theoretically, over 140 analyses can be performed in a working day. The detection limit (signal-to-noise ratio = 3) of this method is about 0.1-0.5 pg per injection for all analytes. The required volume of plasma samples can be less than 100 microliters. Hence, blood loss is minimal, especially in repeated blood sampling. This rapid, simple and sensitive method can, therefore, be used as a routine clinical tool in the simultaneous measurement of plasma homovanillic acid, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Determination of clozapine and desmethylclozapine in human plasma by high-performance liquid chromatography with ultraviolet detection.

A method using reversed-phase high-performance liquid chromatography for the simultaneous determination of clozapine and its desmethyl metabolite in human plasma has been established. Clozapine and N-desmethylclozapine were extracted with n-hexane-isoamyl alcohol (98.5:1.5, v/v). Protriptyline served as the internal standard. The limits of detection for clozapine and desmethylclozapine are 2 and 1 ng/ml, respectively. The sensitivity and precision of this method can be utilized for pharmacokinetic studies and therapeutic drug monitoring regimens.

Adult↗
PubMed1993

Prolonged haloperidol and reduced haloperidol plasma concentrations after decanoate withdrawal.

Haloperidol and reduced haloperidol plasma concentrations were measured in twelve schizophrenic patients upon cessation of haloperidol decanoate (HLD) treatment. Each patient received HLD 100 mg every 4 weeks for five injections. After the fifth injection, HLD was discontinued. Haloperidol and reduced haloperidol plasma concentrations were obtained prior to cessation and at weeks 1, 3, 4, 5, 7, 9, 11, and 13 post-injection. Haloperidol and reduced haloperidol plasma concentrations were assayed by HPLC. Both haloperidol and reduced haloperidol plasma concentrations were detectable 13 weeks post HLD discontinuation. Maximal haloperidol plasma concentrations were observed at one week post cessation and gradually declined. The mean elimination half-life for haloperidol was 27.4 +/- 8.6 days (range 19.0-47.0 days). Reduced haloperidol plasma concentrations declined very slowly. Our results show that both haloperidol and reduced haloperidol plasma concentrations can remain for extended time periods after HLD is discontinued.

Adult↗
PubMed1993

Plasma homovanillic acid and treatment response in a large group of schizophrenic patients.

Plasma levels of homovanillic acid (pHVA), a metabolite of dopamine, were measured in ninety-five Chinese schizophrenic patients free of neuroleptics for at least four weeks. These patients were treated with classical antipsychotics for six weeks. Pretreatment pHVA was positively correlated with the subsequent clinical response (r = 0.408, p < 0.0001). Good responders (BPRS improvement > or = 50%, n = 47) had higher pretreatment pHVA levels than poor responders (BPRS improvement < 50%, n = 48) (15.7 +/- 8.4 ng/ml versus 9.9 +/- 3.7 ng/ml, p < 0.0001). A higher than 15 ng/ml pretreatment pHVA level was associated with a more consistent clinical response to the subsequent treatment. Using a pHVA level of 12 ng/ml as a demarcation point, 72% of patients (34 of 47) who had pHVA > or = 12 responded whereas 65% (31 of 48) who had < 12 did not respond (chi-square = 13.02, p < 0.0001). These results suggest that higher pretreatment pHVA levels may predict a better clinical response to antipsychotics. Based upon the pHVA findings, two hypothetical subtypes of schizophrenia are proposed.

Adolescent↗
PubMed1993

High-level expression of a 56-kilodalton protein gene (bor56) of Rickettsia tsutsugamushi Boryong and its application to enzyme-linked immunosorbent assays.

The 56-kDa protein of Rickettsia tsutsugamushi, which is located on the rickettsial surface, has been shown to be an immunodominant antigen. The gene that encodes the 56-kDa protein of R. tsutsugamushi Boryong (bor56) was cloned. Sequencing revealed an open reading frame of 1,602 bp encoding 534 amino acids with a molecular weight of 56,803. The 56-kDa protein of R. tsutsugamushi Boryong (Bor56) was expressed as a fusion protein with the maltose-binding protein of Escherichia coli by deleting 252 bp from the 5' end of the open reading frame and subcloning it into the StuI site of pIH821. The recombinant fusion protein was purified by amylose column chromatography for application in an enzyme-linked immunosorbent assay to evaluate the ability of the method to detect the antibody to R. tsutsugamushi in human patient sera. By using sera from 100 patients with scrub typhus and 70 patients with other febrile diseases, a high diagnostic sensitivity (95%) and a high diagnostic specificity (100%) were demonstrated, suggesting the suitability of the recombinant antigen for use as an immunodiagnostic tool.

ATP-Binding Cassette Transporters↗
PubMed1993

Identification and characterization of Lyme disease spirochetes, Borrelia burgdorferi sensu lato, isolated in Korea.

Lyme disease spirochetes, Borrelia burgdorferi sensu lato, were identified and characterized for the first time in Korea. Four isolates, designated Konkuk-1, Konkuk-2, Kangwon-3, and KM-4, were made from midgut suspensions of three Ixodes ticks and heart tissue from one mouse, Apodemus agrarius, collected from Chungbuk and Kangwon provinces. The four Korean isolates and B. burgdorferi sensu lato from other geographic areas and biological sources were compared by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis for protein profiles, Western blot (immunoblot) analysis for reactivities with monoclonal and polyclonal antibodies, and agarose gel electrophoresis for plasmid profiles. Two typing schemes using polymerase chain reaction identified three of the isolates as members of group VS461 and one, Kangwon-3, as Borrelia garinii. These results demonstrate the potential for human Lyme disease to occur in some provinces of Korea.

Animals↗
PubMed1993

Rapid diagnosis of scrub typhus by a passive hemagglutination assay using recombinant 56-kilodalton polypeptides.

The genes encoding the 56-kDa polypeptides were amplified by polymerase chain reaction from the genomic DNAs of three serotypes of Rickettsia tsutsugamushi, Gilliam, Karp, and Boryong. The amplified products were cloned into expression vector pIH821, and the recombinant antigens were expressed in Escherichia coli as fusion proteins with maltose-binding protein. The recombinant 56-kDa polypeptides were purified by affinity chromatography for the sensitization of sheep erythrocytes. The recombinant 56-kDa polypeptides were evaluated with 89 serum specimens from health blood donors, 94 serum specimens from scrub typhus patients, and 31 serum specimens from patients with other febrile diseases by a passive hemagglutination assay (PHA). Among the scrub typhus patients diagnosed by indirect immunofluorescent-antibody testing, the antibodies to R. tsutsugamushi were detected in 93 patients (99%). One serum specimen from a healthy person showed a false-positive reaction by this method. The recombinant PHA showed no cross-reactions with sera obtained from other febrile patients with diseases such as murine typhus, hemorrhagic fever with renal syndrome, and leptospirosis. In conclusion, this recombinant PHA could be substituted for the conventional indirect immunofluorescent-antibody test and the immunoperoxidase test.

Antibodies, Bacterial↗
PubMed1993

Pharmacokinetics and pharmacodynamics of clozapine.

The introduction of clozapine has given clinicians a unique agent for treating patients with schizophrenia that is refractory to other neuroleptics. Despite its efficacy, the drug continues to be prescribed with trepidation due to the incidence of agranulocytosis. This article reviews the pharmacokinetic and pharmacological properties of clozapine and the clinical implications for monitoring plasma concentrations. Various assays have been developed for clozapine that include gas-liquid chromatography, radioimmunoassay and high performance liquid chromatography. Only a few studies have examined the pharmacokinetics of clozapine in patients with schizophrenia. These studies have revealed a wide interpatient variability in pharmacokinetic parameters that include: time to reach peak plasma concentrations 1.1 to 3.6h; elimination half-life 9.1 to 17.4h; clearance 8.7 to 53.3 L/h; and a volume of distribution of 1.6 to 7.3 L/kg. Clozapine is metabolised via the hepatic microsomal enzyme system into 2 principle metabolites: demethyl-clozapine and clozapine N-oxide. Urine samples have reported the ratio of clozapine:demethyl:N-oxide to be 1:1:2. The clozapine N-oxide binding affinity with 3H-haloperidol was 4 times lower than clozapine and its conversion back to clozapine is hypothesised. Although the exact pharmacological mechanism of action of clozapine is not fully understood, the drug does possess significant binding affinity for different dopamine receptors, with recent evidence supporting binding to the D4 receptor subtype. Clozapine transiently increases serum prolactin levels with minimal changes in homovanillic acid plasma levels. Limited studies investigating the relationship between clinical response and plasma clozapine concentrations have investigated the range between 100 and 800 micrograms/L. In the treatment of patients with refractory schizophrenia, a minimum concentration of 350 micrograms/L was suggested as needed. The occurrence of agranulocytosis could have a genetic basis and patients should be rigorously monitored during treatment. The incidence of tardive dyskinesia and extrapyramidal side effects is minimal. Clozapine can lower the seizure threshold in a dose- and time-dependent manner. Careful patient selection and monitoring are required when clozapine therapy is used in patients with schizophrenia.

Clozapine↗
PubMed1993

Analysis of antigenic characteristics of Rickettsia tsutsugamushi Boryong strain and antigenic heterogeneity of Rickettsia tsutsugamushi using monoclonal antibodies.

Twenty-four monoclonal antibodies were produced by immunizing BALB/c mice with Rickettsia tsutsugamushi Boryong strain and used for the analysis of antigenic characteristics of R.tsutsugamushi Boryong strain and antigenic heterogeneity of R.tsutsugamushi by indirect immunofluorescent(IF) test. R. tsutsugamushi Kato, Karp, Gilliam, TA686, TA716, TA763, TC586, TH1817, and Boryong were used for the analysis of antigenic heterogeneity of R.tsutsugamushi. Five monoclonal antibodies were reactive with 27-kDa protein, four monoclonal antibodies were reactive with 47-kDa protein, and eight monoclonal antibodies were reactive with 56-kDa protein of R.tsutsugamushi Boryong strain. The reactive protein of seven monoclonal antibodies could not be identified by immunoblotting method. All monoclonal antibodies to 27-kDa protein and three monoclonal antibodies to 47-kDa protein, and five monoclonal antibodies to 56-kDa protein were reactive with three to eight strains among nine strains of R. tsutsugamushi tested. One monoclonal antibody reactive to 47-kDa protein(KI18) and two monoclonal antibodies reactive to 56-kDa protein(KI36, and KI37) reacted with all the strains of R. tsutsugamushi tested. Strain-specific monoclonal antibody(KI58) could be found among antibodies which were reactive with 56-kDa protein. There was no strain which showed same reactivity pattern to these 24 monoclonal antibodies among nine strains. From this results, it could be concluded that Boryong strain is antigenically different from other strains of R.tsutsugamushi and antigenic heterogeneity of R.tsutsugamushi is due to the antigenic diversity of several proteins of R. tsutsugamushi including 56-kDa protein.

Animals↗
PubMed1993

Leptospirosis serology in Korean wild animals.

A study was undertaken on wild animals to determine the seroprevalence of animal leptospirosis in Korea. Using the serum microagglutination test for 19 serogroups, it was shown that two of 26 rats (Rattus rattus) had antibodies to Leptospira canicola. When data for domestic animals were included, the most prevalent (nearly 50%) serogroup was Leptospira canicola.

Agglutination Tests↗
PubMed1993

Comparison of haloperidol plasma concentrations between twice-a-day and once-a-day dosing in Chinese schizophrenic patients.

There is a trend in clinical psychiatric practice to make the dosing schedules of psychotropic medications as simple as possible. In this study, the authors measured the steady state haloperidol plasma levels in patients on different dosing schedules. Twenty-three schizophrenic in-patients were placed on haloperidol with a twice-a-day (10 mg bid) schedule for 14 days; the patients were then changed to a once-a-day (20 mg qd) schedule for another 14 days. Plasma haloperidol (HAL) and reduced haloperidol concentrations were measured at the end of each two-week period. The mean HAL plasma concentrations obtained from the bid and qd dosing schedules were 16.6 +/- 4.9 ng/mL and 12.7 +/- 5.3 ng/mL, respectively. These results are reasonable as the elimination half-life of HAL, as reported by most investigators, is about 24 hours. The present study suggests that a once-a-day dosing schedule in HAL treatment is adequate for most chronic patients.

Adult↗
PubMed1993

[Cerebrospinal fluid lactate, acid-base and gases unbalance in severe head injury].

Arterial PaO2 and cerebrospinal fluid (CSF) lactate, pH, HCO-3, PCO2, and PO2 levels were determined in 52 patients with severe head injury for 1 approximately 5 days. Decreased arterial PaO2 and CSF metabolic acidosis were the most characteristic changes. Sequential analysis of PaO2 and CSF lactate, acid-base unbalance may be used to judge prognosis, to guide treatment, and to improve therapeutic effects. The etiological factors of CSF acid-base unbalance were discussed.

Acid-Base Imbalance↗