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Biomedical subjects

S K Lin

Publications and source records attributed to S K Lin.

At least 91 records · Page 5Linked to original sources
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

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

Histologic reactions to a newly developed calcium phosphate cement implanted in the periapical and periodontal tissues.

A newly developed calcium phosphate cement (CPC), basically composed of tetracalcium phosphate, Ca4(PO4)2O and dicalcium phosphate dihydrate, CaHPO4.2H2O or anhydrous calcium phosphate, CaHPO4, was tested in this study. When combined with water, the cement hardens and produces hydroxylapatite resembling the principal mineral of teeth and bones. Therefore, the CPC should be highly compatible with the body. However, before its clinical application in dentistry, the biocompatibility of CPC in the potential environments of implantation needs confirmation. Eight monkeys were used in our study to test the material in the periapical and marginal periodontal regions. Surgically created periodontal defects were implanted with CPC and hydroxylapatite (HA) (Calcitite 4060). In another application, CPC was pushed into the periapical areas via overfilling of the root canals. Sargenti N2 served as the control material in the periapical test. Generally, only a limited inflammatory response to CPC was found after 6 weeks of implantation in the periodontal area. In the 16-week specimens, the adverse reaction was negligible, and bone regeneration was marked and directly surrounding the CPC. The bone formation activity and biocompatibility in general were found to be even better in the periapical region. The results suggest that the CPC may have a good potential in future clinical applications, although many issues remain to be investigated.

Animals↗
PubMed1989

Pharmacodynamics and pharmacokinetics of haloperidol and reduced haloperidol in schizophrenic patients.

Twelve male chronic schizophrenic inpatients, neuroleptic-free for at least 4 weeks, were given an oral test dose of 10 mg haloperidol (HAL) and reduced HAL (RHAL) in a random order, with a 2-week interval. Two weeks after the last test dose, the patients were given HAL, 5 mg orally twice daily for 7 days. Blood samples were drawn at baseline and between 0.5 and 24 hr after the test doses, and during HAL treatment as well. Plasma drug concentrations and homovanillic acid (HVA) levels were measured with high-performance liquid chromatography using electrochemical detection. HAL, but not RHAL, produced increments in plasma HVA (pHVA) levels at 24 hr after a test dose. pHVA levels remained higher than baseline during HAL treatment. Detectable interconversion between HAL and RHAL was observed in eight patients. The capacity of the reductive drug-metabolizing enzyme system, however, was greater than that of the oxidative processes. The plasma RHAL:HAL ratios on days 6 and 7 were higher than and positively correlated with those at Tmax after a single dose of HAL and were negatively correlated with the HAL:RHAL ratios at Tmax after a single dose of RHAL. Thus, both reductive and oxidative drug-metabolizing systems probably contribute to individual differences in plasma RHAL:HAL ratios in HAL-treated schizophrenic patients.

Adult↗
PubMed1986

Effect of orally administered celiprolol in patients with chronic atrial fibrillation.

The heart rate increase induced by dynamic exercise in patients with chronic atrial fibrillation is competitively attenuated by beta-blockade. The influence of oral celiprolol on exercise induced tachycardia was evaluated in 23 patients with chronic stable atrial fibrillation in a dose-titration study. This was succeeded by a placebo-controlled double-blind, crossover multi-center trial. During the dose-titration phase each patient underwent a single-blind three week dose escalation period-taking celiprolol 200 mg once daily for one week, celiprolol 400 mg once daily for the third week. After a one week placebo washout, patients then entered a double-blind crossover phase, consisting of one week each of placebo or celiprolol according to a pre-determined randomization. After one week of placebo washout, each patient was crossed-over. In 21 patients celiprolol reduces exercise-induced increased heart rate by approximately 35% when compared with placebo. These results indicate that celiprolol should be effective in controlling the exercise-induced increase in heart rate in patients with chronic atrial fibrillation. In addition, results of 24 h ambulatory ECG monitoring (Holtor monitoring) indicate that celiprolol reduces the ventricular premature contractions.

Administration, Oral↗
PubMed1986

Clinical cardiac electrophysiologic study of celiprolol.

The objective of the study was to evaluate the acute effect of intravenous celiprolol on the electrophysiologic properties of the cardiac conduction system in man and to assess potential problems in terms of its causing heart block or sinus bradycardia. Eight patients with controlled coronary artery disease and hypertension but without conduction system disease were studied. All cardiac drugs e.g., digoxin, sympathomimetics and other beta blockers were discontinued prior to entering the study. Surface ECG leads I, AVF, and Vi were applied to each patient, and the ECG was continuously displayed on an oscilloscope. A quadripolar stimulating electrode (7F) was inserted percutaneously and positioned in the high right atrium and a tripolar or bipolar His bundle recording catheter was positioned cross the tricuspid valve. The atrial and His bundle electrograms were recorded on a direct writing recorder. After completion of the baseline electrophysiologic (EP) measurements, in an open fashion, celiprolol (0.1 mg/kg) was administered intravenously at the rate of 1 mg/min into each of the five patients. The complete battery of the EP measurements were repeated immediately following completion of the infusion. Preliminary data in eight patients demonstrated no significant effect of celiprolol on the cardiac conduction system.

Adult↗
PubMed1979

Kinetics of drug-drug interactions: biliary excretion of iodoxamic acid and iopanoic acid in rhesus monkeys.

The dynamic method originally developed for studying the capacity-limited kinetics of the cholecystographic agents iodoxamic acid and iopanoic acid was applied to study the in vivo interactions of these two compounds following coadminstration in the monkey. Results indicate that these interactions are complex. The compounds appear to compete for plasma protein binding sites as well as for binding sites on intrahepatic proteins. The biliary excretion data apparently fit the "ligand exclusion" model in which iopanoic acid acts as an inhibitor and competes with iodoxamic acid for binding to either of two identical sites within the liver. This competition probably is the rate-limiting step in the liver's overall elimination of these radiographic contrast agents.

Animals↗
PubMed1978

Pharmacokinetics of iodoxamic acid in rhesus monkey: biliary excretion, plasma protein binding, and enterophepatic circulation.

The previously reported steady-state method allowed estimation of the capacity-limited pharmacokinetics of the cholangiographic agent, iodipamide. To circumvent the long time period required to establish each steady-state level, a dynamic method was applied to the study of the rate processes involved in the hepatic uptake and biliary excretion of a new cholangiographic agent, iodoxamic acid, in rhesus monkeys. The dynamic method has the advantage that the pharmacokinetic parameters involved in capacity-limited hepatic uptake or biliary excretion can be obtained from a single infusion experiment. The V max was 1.03 +/- 0.25 mumoles/kg/min (mean +/- SD); Km varied from animal to animal and ranged from 1.5 to 16.4 micrometer. Protein binding was estimated using equilibrium dialysis. The Freundlich isotherm yielded a linear plot when the natural logarithm of unbound iodoxamic acid concentration in plasma was plotted against the natural logarithm of its blood concentration. The plasma protein binding data also could be fitted to the Langmuir isotherm, presuming two independent classes of binding.

Animals↗
PubMed1977

Iodipamide kinetics: capacity-limited biliary excretion with simultaneous pseudo-first-order renal excretion.

Iodipamide was infused into three dogs with bile fistulas to achieve various steady-state blood levels. When using ultracentrifugation techniques, iodipamide was found to be highly bound to plasma protein. The total blood clearance was low relative to hepatic blood flow. For either the whole blood concentration or the unbound concentration of iodipamide, the biliary excretion was shown to be capacity limited with a transport maximum, Tm, of approximately 1.0mumole/kg/min. The steady-state renal excretion rate, plotted against the whole blood concentration of iodipamide, resulted in a concave ascending curve, which could lead to the false conclusion that iodipamide was undergoing active renal tubular reabsorption. However, when corrected for plasma protein binding, a linear relationship was obtained, suggesting that the renal excretion of iodipamide is a pseudo-first-order process. The Michaelis-Menten parameters for the extrarenal elimination, when calculated using the whole blood concentration of iodipamide, led to a similar discrepancy compared to the parameter estimates obtained from biliary excretion rate data. This discrepancy can be eliminated when one uses the unbound concentration of iodipamide in the parameter estimates.

Animals↗
PubMed1975

Microbial transformation of aspidospermine.

Thirty actinomycetes were isolated from soil samples and screened for their ability to modify the structure of aspidospermine. One actinomycete culture converted aspidospermine into O-demethylaspidospermine but failed to modify N-deacetylaspidospermine, N-ethyl-N-deacetylaspidospermine, 7-methoxyindole, and 7-methoxytryptophan.

Actinomycetales↗
PubMedDate not supplied

Correlation between Helicobacter pylori infection and gastrointestinal symptoms in pregnancy.

Nausea, vomiting, and other dyspeptic symptoms are common in pregnancy. This hospital-based, cross-sectional study was designed to determine the role of Helicobacter pylori infection in gastrointestinal (GI) symptoms during pregnancy. Standardized verbal scales were used to evaluate the frequency and severity of GI symptoms in 54 women whose pregnancies were in the first 16 gestational weeks. H. pylori infection was defined as a positive serum immunoglobulin G result on an immunochromatographic assay. The H. pylori seropositivity rate was higher in the pregnant women (69%) than in the general population (approximately 50%-55%), but seropositivity did not correlate with clinical symptoms. Moreover, no specific patterns of GI symptoms were uncovered in the H. pylori-infected patients. Maternal age, body weight, parity, gestational week, and educational level were not associated with H. pylori infection; neither were the prevalence and severity of GI symptoms.

Adult↗
PubMedDate not supplied

A clinical study of schizophrenic suicides. 42 cases in Taiwan.

A clinical study of 25 male and 17 female schizophrenic suicides is presented. Jumping from a height was the most common method used. The 42 suicidal schizophrenics in Taiwan were compared with both 84 sex- and age-matched and 60 5-year illness course non-suicidal schizophrenic control groups. The suicidal schizophrenics were not significantly different from the non-suicidal counterparts of both control groups with regard to age, sex, ethnicity, religion, educational background, the presence of suicide cases in the family history, and the presence of insight, but were significantly different in characteristics of a history of previous suicide attempts, presence of psychotic symptoms during their final month, depression during their final month, a history of depression, a history of previous psychiatric hospitalizations, and the number of hospitalizations. We discuss the findings from this study and others in the literature in the context of the different clinical and socio-cultural backgrounds of these Taiwanese schizophrenic suicides.

Adult↗
PubMedDate not supplied

Saturation kinetics of iodipamide.

To characterize the saturation kinetics of iodipamide, timed samples of blood, urine, and bile were taken from two unanesthetized dogs infused with iodipamide at increasing rates to achieve various steady state blood concentrations. Biliary excretion rate of iodipamide reached an asymptote with increasing blood concentration, indicating a biliary transport maximum (Tm) of 15.2 to 16.2 mgI/min. Urinary excretion was not a pure, first order process and urinary excretion rate was higher than the glomerular filtration rate corrected for plasma protein binding, suggesting that active tubular secretion may play a part. Extrarenal elimination followed Michaelis-Menten kinetics. Estimates of maximum rate (Vm) and Michaelis-Menten constant (Km) were obtained graphically. The estimated values of Vm were 4 to 6 times that of biliary Tm. In acute infusion experiments the iodipamide excreted in the bile and urine and that remaining in the organs analyzed accounted for only a fraction of the dose administered; no significant accumulation of iodipamide was found in the liver.

Animals↗
PubMedDate not supplied

Recirculation of iopanoic acid after conjugation in the liver.

The purpose of the investigation was to determine if an enterohepatic recirculation occurred for the metabolite of iopanoic acid. The major metabolite of iopanoic acid (Telepaque) in dog bile is the glucuronide conjugate. The identification and quantitation of glucuronide conjugate was accomplished by elemental analysis, paper chromatography, thin layer chromatography, fluorescent excitation analysis, and high pressure liquid chromatography. The stability of iopanoic acid glucuronide in refrigerated dog bile was confirmed. Known amounts of the glucuronide conjugate were instilled into the duodenum of 8 awake adult dogs, and bile collected for 8 hours. Between 19% and 53% (average 31%) of the administered dose was recovered in bile, thereby documenting the presence of an enterohepatic recirculation of conjugated iopanoic acid. The slow rise and plateau of the excretion curve suggests that either the compound is absorbed slowly, or that absorption depends upon deconjugation in the gut. The implications are discussed.

Animals↗