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Biomedical subjects

I W Chen

Publications and source records attributed to I W Chen.

At least 19 recordsLinked to original sources
PubMed1992

Quantitation of a new cholecystokinin and gastrin receptor antagonist (L-365,260) in dog and rat plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) procedure has been developed for the quantification of L-365,260 (I), a cholecystokinin and gastrin receptor antagonist, in dog and rat plasma. The method involves liquid-liquid extraction and HPLC with ultraviolet detection. Standard curves were linear over the range 7.5-2000 ng/ml for rat and dog plasma. The method is reproducible and reliable with a detection limit of 7.5 ng/ml in biological fluids. The mean coefficients of variation for concentrations within the range of the standard curve range were 3.84 and 2.56%, respectively, for intra-day analysis and 4.48 and 4.26%, respectively, for inter-day analysis. Application of the development was successfully demonstrated by quantifying the concentration of I in both dog and rat plasma samples following an intravenous or oral dose of 5 mg/kg I.

Animals↗
PubMed1992

Dose-dependent toxicokinetics of L-689,502, a potent human immunodeficiency virus protease inhibitor, in rats and dogs.

L-689,502, N-[2(R)-hydroxy-1(S)-indanyl]-5(S)-(1,1-dimethylethoxy- carbonylamino)-4(S)-hydroxy-6-phenyl-2(R)-(4-[2-(4- morpholinyl)ethoxy]phenyl)methyl hexanamide, is a potent inhibitor of human immunodeficiency virus-1 protease. The effect of dose on the elimination kinetics of L-689,502 was studied in rats and dogs. After i.v. administration, total plasma clearance of L-689,502 in rats decreased with increasing dose; the clearance decreased from 181 ml/min/kg at 1 mg/kg to 86 ml/min/kg at 20 mg/kg. Similar results were observed in dogs; clearance fell from 29 ml/min/kg at 0.5 mg/kg to 17 ml/min/kg at 10 mg/kg. Bile flow in rats was retarded in a dose-dependent manner after a single i.v. injection of L-689,502. The cholestatic effect was reversible and maximal at 5 mg/kg i.v. Consistent with the cholestatic effect, L-689,502 caused an increase in serum levels of aminotransferase. After i.v. administration of L-689,502 (10 mg/kg), alanine aminotransferase increased from 50 to 370 IU/liter and aspartate aminotransferase from 120 to 700 IU/liter. Moreover, pretreatment of rats with L-689,502 resulted in a significant decrease in the elimination kinetics of antipyrine and diflunisal, as well as of L-689,502 itself. Collectively, these results suggest that the dose-dependent kinetics of L-689,502 in rats and dogs are more likely due to hepatotoxicity caused by the drug than to capacity-limited metabolism.

Acetaminophen↗
PubMed1991

Dose-dependent pharmacokinetics of MK-417, a potent carbonic anhydrase inhibitor, in experimental polycythemic and anemic rats.

MK-417 is a potent carbonic anhydrase inhibitor currently under clinical investigation as a topical ocular hypotensive agent. While present in most of the tissues, carbonic anhydrase predominates in red blood cells. Earlier studies from our laboratory have demonstrated that carbonic anhydrase plays an important role in the elimination kinetics of MK-417 and that the enzyme can be saturated when MK-417 exceeds the stoichiometric concentration of the enzyme. Since carbonic anhydrase is an intracellular enzyme in erythrocytes, conditions which may change the hematocrit can alter the load of MK-417 needed to saturate carbonic anhydrase. It is, therefore, important to determine the effects of anemic and polycythemic states on the pharmacokinetics of MK-417. The anemic state in rats was obtained by replacing whole blood with donor plasma (12-15 ml), while polycythemia was induced by infusion of 12 to 15 ml of whole blood. At low doses (0.05 and 0.1 mg/kg), the pharmacokinetic parameters for MK-417 remained unchanged and there were no significant differences in the pharmacokinetic parameters among the anemic, polycythemic, and normal rats. The total blood clearance and apparent volume of distribution were increased markedly when the dose exceeded 0.2 mg/kg in anemic rats and 0.5 and 1 mg/kg in normal and polycythemic rats, respectively. Clearly, the dose of MK-417 required to saturate the enzyme was different among the three groups of animals. However, the terminal half-life was dose independent and not influenced by hematocrit.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗
PubMed1990

High-performance liquid chromatographic determination of cilastatin and its major metabolite N-acetylcilastatin in rat plasma, urine and bile.

A new high-performance liquid chromatographic method coupled with solid-phase (C8) sample extraction has been developed for the simultaneous quantification of cilastatin and its major metabolite N-acetylcilastatin in rat plasma, urine and bile. The method is linear, reproducible and reliable with a detection limit of 1 microgram/ml in all three fluids. Plasma concentrations of cilastatin and N-acetylcilastatin at selected time intervals and biliary and urinary recoveries of cilastatin and N-acetylcilastatin following an intravenous dose of 10 mg/kg cilastatin are presented.

Animals↗
PubMed1990

Serum osteocalcin measurements in prostate carcinoma patients with skeletal deposits shown by bone scintigram: comparison with serum PSA/PAP measurements.

The correlation of technetium-99m-HMDP bone scintigraphic findings, serum osteocalcin as a measure of bone turnover and prostate-specific antigen (PSA) and/or prostate acid phosphatase (PAP) was determined in 19 men with bone metastasis due to prostatic carcinoma. Six of the 19 patients with metastases on bone scan showed elevation of osteocalcin. These patients had extensive metastatic disease. All 19 men with positive bone scans had high serum PSA and/or PAP levels. Serum osteocalcin measurement is less sensitive to detection of bone deposits than PSA/PAP measurements (p less than 0.0008).

Acid Phosphatase↗
PubMed1990

[Investigation on the relation between hepatitis B virus knowledge and needle-stick injury of hospital personnel].

The purposes of this study are: (1) to understand the knowledge of Hepatitis B virus known by hospital personnel. (2) to investigate the injury caused by accidental needle stick and its frequency. (3) to identify those personnel and job activities at high risk of needlestick injuries, to assess current medical management of these injuries in our hospital, and also to develop rational guidelines for prevention, based on the findings. 510 effective questionnaires were collected and analyzed by SPSS analytical system. The result of the present study showed that 77.1% hospital personnel had been experienced by needlestick injury. Most injuries occurred during recapping the needle after use and disposal of used needle. 92.7% hospital personnel felt that hospital should provide all the expense needed for Hepatitis B virus immunoglobulin while needle-stick injuries happened within the hospital. 86.3% of them felt that hospital should establish a special committee to evaluate and manage all the needle-stick injuries events. This study also showed that hospital personnel who have been working less than five years and their age between 21-30 can pay more attention to this kind of event. Dietitian and doctor got higher score in this study. Hospital personnel who were infected by Hepatitis B virus scored higher than uninfected one. In conclusion, we recommend not recapping used needles and making widely available and promoting use of an efficient needle disposal system. And we hope that those who have never been infected by Hepatitis B virus should accept vaccination as soon as possible.

Accident Prevention↗
PubMed1988

Hematoporphyrin derivative uptake and photodynamic therapy in pancreatic carcinoma.

Little information is currently available concerning the uptake of porphyrins by pancreatic tumors, or the effect of photodynamic therapy (PDT) on pancreatic cancer. In Syrian golden hamsters (n = 33), the organ distribution of 125I-labeled dihematoporphyrin ether (DHE) was studied in a pancreatic cancer model. In the same animal model the effect of PDT was studied using a gold vapor laser for energy delivery 3 hr after the injection of DHE (n = 7). DHE was 2.4 times more concentrated in the pancreatic tumor than in the nontumorous pancreas at 3 hr. Simultaneously there was a considerable accumulation of DHE in the surrounding gastrointestinal tract, causing perforation of the duodenum and jejunum with resultant death in four (57%) animals after PDT. Photodynamic therapy caused extensive tumor necrosis without any obvious effect on the nontumor-bearing pancreas. Damage to the surrounding tissue in the hamster indicates that precautions should be taken if PDT is to be used clinically in pancreatic cancer. Intratumoral injection of DHE may give higher drug concentrations with greater specificity for tumor treatment.

Adenocarcinoma↗
PubMed1987

Calcium, phosphorus, magnesium, and calcitonin concentrations in the serum and cerebrospinal fluid of children.

Mineral metabolism in the cerebrospinal fluid (CSF) of children is poorly understood. Recent reports have suggested a neuroregulatory role for calcitonin. We examined the hypotheses that in children (1) CSF levels of calcium and phosphorus might be low, (2) CSF levels of magnesium might be higher than serum levels of magnesium, and (3) immunoreactive calcitonin might be present in the CSF. We examined serum and CSF samples of 45 children, aged 8 days to 16 years, undergoing spinal taps for suspected meningitis or as part of leukemia therapy. Both serum and CSF levels of calcium correlated with those of magnesium. There was no correlation for CSF levels vs serum levels of calcium, magnesium, or phosphorus. The CSF levels of calcium and phosphorus were lower than the serum levels of these elements, but the CSF levels of magnesium were higher than the serum levels of magnesium. Calcitonin was detected in the CSF of 8% of samples assayed (range, 14 to 175 ng/L [14 to 175 pg/mL]). Two of these five samples had bacteriologically proven meningitis, and two samples were from patients less than 2 months of age. The CSF levels of calcitonin did not correlate with the serum levels of calcitonin. Thus, in children CSF levels of calcium and phosphorus are low, CSF levels of magnesium are higher than the serum levels, and the level of immunoreactive calcitonin is usually not present in the CSF but possibly is elevated in meningitis and early infancy.

Adolescent↗
PubMed1987

Pathogenesis of early neonatal hypocalcemia: studies of serum calcitonin, gastrin, and plasma glucagon.

In 64 maternal-infant pairs, we tested the hypotheses that serum calcitonin, serum gastrin, and plasma glucagon concentrations are elevated in infants at risk for early neonatal hypocalcemia, and that elevated serum gastrin and plasma glucagon result in elevated serum calcitonin and low serum calcium values in neonates. Serum Ca declined significantly in neonates at 24 hours of age, and was inversely correlated with serum calcitonin. Cord serum calcitonin, gastrin, and plasma glucagon concentrations rose significantly at 24 hours of age. Cord calcitonin was significantly higher in preterm compared with term infants, and there was no significant difference between asphyxiated and nonasphyxiated preterm neonates; in term neonates cord calcitonin concentration was inversely correlated with Apgar scores at 1 and 5 minutes. Cord calcitonin was not correlated with cord gastrin or glucagon. Cord and 24-hour gastrin and glucagon values were not related to prematurity; cord glucagon, but not gastrin, was related to birth asphyxia. We conclude that (1) serum calcitonin, gastrin, and plasma glucagon values rise postnatally; cord calcitonin is elevated in preterm and in asphyxiated term infants; serum calcitonin concentration does not correlate with the elevated serum gastrin and plasma glucagon values; and at 24 hours of age, decreased serum Ca is correlated with serum calcitonin, and hence calcitonin might play a role in the pathogenesis of early neonatal hypocalcemia.

Apgar Score↗
PubMed1987

Myoglobin as an early indicator of acute myocardial infarction.

The ECG and the determination of serum enzymes creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) may be falsely normal early in acute myocardial infarction. Myoglobin, an oxygen-carrying protein found in cardiac muscle and striated skeletal muscle, presents an attractive alternative to CPK and LDH in the emergency department setting for identification of acute myocardial infarction. Myoglobin levels may be elevated in the serum within one hour after myocardial cell death with peak levels reached within four to six hours. We report a study of 59 patients presenting to a community hospital with chest pain and subsequent hospitalization. Twenty-one had an acute myocardial infarction. Presenting (0 hour) myoglobin determination was positive in 13 of 21 individuals, while CPK-MB was positive in only three. Serum myoglobin elevation at three hours identified all 21 patients with myocardial infarction with the CPK-MB determination positive in 19. Serum myoglobin elevation may permit early identification of myocardial infarction, with subsequent verification using CPK-MB determination, allowing appropriate intensive care admission for careful monitoring of these patients.

Adult↗
PubMed1987

Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis.

Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of 14C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis.

Animals↗
PubMed1987

Variations in serum thyroxine concentrations with time after an oral replacement dose.

Serum thyroxine concentrations were measured sequentially in eight healthy male volunteers after the oral administration of one of two brand name, commercially available thyroxine tablets. In all cases, levels peaked at 2 hours and did not return to baseline values until 24 hours after dosing. From 2 through 10 hours, statistically significant elevations in serum thyroxine concentrations were observed. Such fluctuations may be important in evaluating laboratory results in patients receiving replacement doses of thyroxine.

Administration, Oral↗
PubMed1987

Differential effects of phenobarbital on ester and ether glucuronidation of diflunisal in rats.

The relative contribution of ether and ester glucuronidation to diflunisal metabolism was assessed by studying the effects of enzyme inducers, phenobarbital (PB), 3-methylcholanthrene (3-MC) and beta-naphthoflavone (BNF). Treatment with either PB, 3-MC or BNF increased markedly the unbound intrinsic clearance of diflunisal. Saline-treated control rats showed a greater unbound intrinsic clearance of diflunisal than oil-treated controls indicating that repetitive treatment with oil had an effect on enzyme activity. Treatment with 3-MC and BNF appeared to cause a decrease in the biliary clearance of ether and ester glucuronide, but PB had little effect on the biliary clearance of glucuronides. Rats pretreated with PB showed a 3-fold increase in the fractional metabolite formation clearance of ether glucuronide and a 2-fold increase in the fractional metabolite formation clearance of ester glucuronide, suggesting differential effects of PB on ester and ether glucuronidation. A similar trend, but to a smaller extent, was also observed for 3-MC- and BNF-treated rats. These results suggest the possibility of selective induction of multiple forms of UDP-glucuronyltransferase involved in metabolism of diflunisal.

Animals↗
PubMed1985

Clinical utility of serum prostatic acid phosphatase measurements for detection (screening), diagnosis, and therapeutic monitoring of prostatic carcinoma; assessment of monoclonal and polyclonal enzymes and radioimmunoassays.

Serum prostatic acid phosphatase (PAP), measured by three different technics, was used to screen 560 men over 50 years of age for prostatic cancer. All three PAP procedures failed to detect the one subject found to have prostatic cancer on physical examination and confirmed by biopsy, and all assays had a significant number of "falsely" elevated PAP levels. Four PAP assays were assessed in 80 men undergoing prostatic biopsy/removal in whom histologic examination of prostatic tissue was made. Clinical sensitivity and specificity for detecting those patients with and without prostatic cancer ranged from 20-57% and 54-95%, respectively, with the monoclonal enzyme immunoassay being the most sensitive but the least specific, and the traditional enzyme assay being the most specific but insensitive. In men with diagnosed prostatic cancer undergoing radiation or chemotherapy, the assays were useful in distinguishing between those with active and inactive disease. The authors conclude that serum PAP assays, irrespective of the type of procedure used, has no place in screening for prostatic cancer, a minimal role in establishing a definitive diagnosis, but a useful role in monitoring therapy.

Acid Phosphatase↗
PubMed1979

1,25-Dihydroxyvitamin D3 in childhood hepatic osteodystrophy.

Osteodystrophy frequently accompanies severe childhood hepatobiliary disease. Proposed causes include malabsorption of vitamin D and calcium, and diminished 25-hydroxylation of vitamin D. Two children, ages 23 and 35 months, with radiographic and biochemical evidence of rickets with extrahepatic biliary atresia, were treated with 1,25-dihydroxyvitamin D3. The minimal effective therapeutic dose and efficacy of 1,25-(OH)2D3 in the treatment of rickets associated with severe childhood hepatic disease were determined. Oral 1,25-(OH)2D3 was ineffective at doses of 0.10 microgram/kg/day. Parenteral doses of 0.20 microgram/kg/day effectively produced radiographic, bone mineral (photon absorptiometric), and biochemical evidence of healing. The need for four times the physiologic dose of 1,25-(OH)2D3 by the parenteral route suggested enhanced catabolism of, or end-organ resistance to, 1,25-(OH)2D3 in our patients with severe cholestatic liver disease treated with phenobarbital.

Bile Ducts↗
PubMed1979

A commercial digoxin radioassay modified for use as an emergency ("stat") procedure.

A recent "stat" procedure recommended by the manufacturer for use with a commercial digoxin radioassay involves doubling the amount of antibody used in the regular procedure, to compensate for the decrease in binding that results from use of a shorter (10 min) incubation. This has two obvious disadvantages: increased material cost and decreased sensitivity because of the increase in the binding capacity of the assay. In our modified procedure, we kept the binding capacity constant by decreasing the volume of the incubation mixture without increasing the amount of antibody. Total binding and the rate of binding on 10-min incubation are 50.4 and less than 1.3% per minute, respectively. Results by our modified stat procedure compare well with those by the manufacturer's suggested regular procedure in terms of sensitivity, accuracy, and precision, and are more sensitive and economical than those by the manufacturer's suggested stat procedure.

Digoxin↗
PubMed1979

A statistical method for determining normal ranges from laboratory data including values below the minimum detectable value.

Determination of normal ranges from laboratory data containing undectable values is a frequently encountered problem in the radioimmunoassay of peptide hormones. In the past, such determinations usually have been based on the mid-point method or the one-end Winsorized method. A graphic method involving the use of probability paper has also been reported. We propose that the maximum-likelihood estimation is a more appropriate statistical method for the determination of normal range from this type of data (Type I censored data). With this method, the mean and standard deviation, and hence the tolerance limits, can be estimated. We used the maximum-likelihood estimation method to determine the normal range of serum thyrotropin values obtained from 93 healthy subjects, based on a log normal distribution. Although the serum thyrotropin content was undetectable in 14% of the subjects, a normal range could be calculated. Using tolerance limits for 95% coverage of the population with 90% confidence, we calculated the normal range of thyrotropin to be 0.51-5.75 milliunits/L, with a mean value of 1.71 milliunits/L, and predicted that 91.4% of undetectable serum thyrotropin values will fall within the normal range.

Humans↗