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Biomedical subjects

W L Chen

Publications and source records attributed to W L Chen.

At least 19 recordsLinked to original sources

Chromosomal study in lymphocytes from subjects living or working in buildings constructed with radioactively contaminated rebar.

It has recently been found that many buildings in Taiwan were constructed with radioactively contaminated rebar, which raised great concern among the residents as well as governmental officials. In order to investigate the possible cytogenetic damage to the residents of contaminated buildings, a G-banding method was carried out on the lymphocytes of 30 radiation-exposed individuals from four families and one office building, as well as 15 control individuals from laboratory personnel. The estimated cumulative radiation doses for the exposed people range from 19.63 to 280.50 mSv. Altogether, 13 females and 17 males belonging to the radiation-exposed group, and 7 females and 8 males in the control group, were included in this study. With the exception of one sample, at least 500 metaphase spreads were scored and analyzed for each individual. All the recognizable structural aberrations of chromosomes or chromatids were recorded and statistically analyzed. Comparison of either percentage of cells with chromosome aberrations or number of aberrated chromosomes per 100 cells between the radiation-exposed and the control groups manifested insignificant differences (p = 0.1145 and 0.0766, respectively). In addition, the chromosomal regions close to the centromere were found to break more frequently than elsewhere in the genome.

Adolescent

Prenatal diagnosis of partial trisomy 12 and partial trisomy 21 due to a 3:1 segregation of maternal reciprocal translocation t(12;21) (p13.3;q21).

We describe the prenatal diagnosis and fetal phenotype of partial trisomy 12 (p13.3-pter) and partial trisomy 21 (pter-q21) due to a 3:1 segregation with tertiary aneuploidy transmitted from a maternal reciprocal translocation 12;21. Genetic amniocentesis of a 39-year-old gravida 2, para 1 woman at 19 weeks' gestation due to advanced maternal age revealed an unusual karyotype of 47,XY,+der(21)t(12;21)(p13.3;q21)mat. The pregnancy was terminated at 24 gestational weeks. The proband postnatally displayed by dysmorphic features of a round flat face with prominent cheeks and high forehead, upward slanting palpebral fissures, epicanthic folds, hypertelorism, a short nose, a broad and depressed nasal bridge, anteverted nares, a deformed philtrum, an open mouth, thin upper vermilion and broad everted lower lip, low-set ears with prominent anthelix and deep concha, broad hands with simian creases, a short neck, and cryptorchidism. The association of the involved chromosomal segments with the phenotype of Down's syndrome and trisomy 12p syndrome is discussed.

Adult

Increased urinary excretion of sulfated 3,3',5-triiodothyronine in patients with nodular goiters receiving suppressive thyroxine therapy.

Increased serum 3,3',5-triiodothyronine sulfate (T3S) levels have been detected in various pathophysiologic states. However, little is known about T3S concentrations in other biological fluids. By employing a highly sensitive, specific, and reproducible radioimmunoassay (RIA), we measured T3S in the serum and urine of 20 premenopausal women with benign nodular goiters before and after administration of thyroxine for 6 months (T4; 3.2 micrograms/kg/day). Serum T3 concentrations did not change significantly after treatment (2.0 vs. 1.7 nmol/L; p > 0.05). However, the mean serum T4 and free T4 concentrations were significantly higher after treatment (138 vs. 88 nmol/L and 28 vs. 17 pmol/L; p < 0.01, respectively). Serum thyroid stimulating hormone (TSH) levels were significantly reduced after T4 treatment (0.13 vs. 0.66 mU/L, p < 0.01) and the serum levels of T3S were significantly increased after treatment (82 vs. 45 pmol/L; p < 0.01). A good correlation was observed between increased serum T3S and T4 concentrations (r = 0.66; p < 0.001). The sulfoconjugate of T3 was significantly increased in creatinine-corrected urine after treatment (606 vs. 253 pmol/umol Cr.; p < 0.01). There was a significant correlation between increased creatinine-corrected urine T3S and increased serum free T4 (r = 0.65; p < 0.001). In summary, significant increases in serum and urine T3S levels were noted in T4-treated patients with subnormal serum TSH and borderline elevated T4. We thus conclude that the sulfation pathway may play a role in the homeostasis of thyroid hormone metabolism in T4-treated subjects with relative hyperthyroxinemia. In addition, the creatinine-corrected urine concentrations of T3S may serve as an index for the evaluation of T4-treated patients with elevated levels of T4.

Adult

Changes in thyroid hormone metabolism in exertional heat stroke with or without acute renal failure.

The effects of exertional heat stroke (ExHS), with or without acute renal failure (ARF), on thyroid hormone metabolism were investigated. Eighteen ExHS patients were recruited and divided into two groups based on the presence or absence of ARF. Eleven age-matched healthy subjects served as a control group. Serum values of T3, T4, TSH, free T4 (FT4), rT3, and sulfated T3 (T3S) were measured in these groups during the acute and recovery stages of ExHS. Serum T3, T4, and FT4 levels were reduced, with reciprocal increases in rT3 and T3S levels as the severity of ExHS increased. The following mean levels of thyroid hormones were found (controls vs. ExHS without ARF vs. with ARF): T3, 1514 vs. 1164 vs. 393 pmol/L (P < 0.05 each); T4, 97 vs. 79 vs. 49 nmol/L (P = NS and P < 0.05, respectively); FT4, 20.5 vs. 19.5 vs. 19.0 pmol/L (P = NS each); rT3, 371 vs. 617 vs. 805 pmol/L (P < 0.05 and P = NS, respectively); and T3S, 30.1 vs. 34.2 vs. 71.1 pmol/L (P = NS and P < 0.05, respectively). The serum TSH levels were not significantly different among the three groups. Significantly negative correlations were found between serum creatinine and T3 (r = -0.75; P < 0.001) and T4 levels (r = -0.65; P < 0.001), whereas no relationship was noted between serum creatinine and rT3 values (r = 0.11; P < 0.05). In contrast, a correlation was observed between serum glutamic pyruvic transaminase and rT3 (r = 0.45; P < 0.01). Thyroid function tests returned to normal after patients recovered. In conclusion, our results show that patients suffering from ExHS, with or without ARF, displayed altered serum thyroid function in proportion to the severity of their condition. No significant changes in serum levels of rT3 were observed between the two groups, whereas a positive relationship was observed between serum rT3 and serum glutamic pyruvic transaminase values, suggesting that the changes in serum rT3 levels were more dependent on extrarenal illness than on renal disease per se. The moderate increase in serum T3S levels found in patients suffering from both ExHS and ARF may represent a decrease in tissue 5'-monodeiodinase activity as found in other nonthyroidal illnesses. A return of serum thyroid function tests to normal values after recovery from ExHS suggests that the low T3 state may play a protective role to prevent undesirable catabolic effects. Replacement therapy is thus not recommended.

Acute Kidney Injury

Maturation of hepatic desulfation activity in developing rats.

The present study was carried out to further characterize the maturation of desulfation activity in developing rats. High levels of 3,3',5-triiodothyronine sulfate (T3S) were found in rat fetal serum whereas 3,3',5-triiodothyronine (T3) levels were low. The ratio of T3S/T3. was dramatically reversed in the rat maternal circulation. Maternal rats had higher desulfation activity than did near-term fetuses. Desulfation of T3S to T3 by microsomes of fetal and maternal livers were studied by incubating microsomes with T3S as a substrate. Desulfated T3 was measured by radioimmunoassay. The Km and Vmax values for desulfation of T3S to T3 by hepatic microsomes in different age groups were compared. Little desulfation activity was found in hepatic microsomal preparations from fetal rats compared with newborn rats. There was a trend of increasing desulfation activity in rats after birth until 1 month of age, although this was not significant. A surge of desulfating activity was observed between the 1- and 2-month old groups. The K(m) values for T3S desulfation activity were similar in all age groups. The Vmax values for the T3S to T3 desulfation activity progressively increased after birth until 2 months of age. The Vmax of the latter group, however, was comparable to that of the maternal group. These results suggest that the maturation of desulfation activity in the microsomal preparations from rat livers is completed by 2 months of age and is mainly due to increased enzyme capacity. Sulfation-desulfation of T3 may play a role in the thyroid hormone regulation of developing mammals.

Age Factors

Identification of 3,3'-T2S as a fetal thyroid hormone derivative in maternal urine in sheep.

We measured 3,3'-diiodothyronine sulfate (T2S) in serum and urine (n = 5-6) obtained from euthyroid fetal (94-145 days of gestation, term = 150 days), newborn, and adult sheep and in serum and urine samples from ovine fetuses 13 days after total thyroidectomy conducted between 110 and 113 gestation days (n = 5). Sham-operated twin fetuses served as controls (n = 5). Mean serum T2S concentrations increased progressively from 94 days (74 ng/dl) to 130 days (420 ng/dl), decreasing thereafter to 145 days (197 ng/dl). T2S concentrations in fetal urine peaked at 110 days (117 ng/dl). In hypothyroid fetuses, mean serum and urine T2S were 60 and 53% of control values. To assess the possibility that the T2S in maternal serum/urine is derived from fetal serum 3,5,3'-triiodothyronine (T3), we measured T3, T3 sulfate (T3S), and T2S in fetal serum and in maternal serum and urine after bolus infusion of T3 to the fetus (n = 4). Additionally, T3, T3S, and T2S concentrations were measured in maternal serum and urine after T3 infusion to the maternal ewes (n = 4). Fetal T3 infusion rapidly increased fetal serum T3S and T2S. Maternal serum and urine T3S and T2S concentrations increased, whereas T3 concentrations remained unchanged. Maternal T3 infusion increased in serum and urine T3S and T2S levels, but the levels, relative to T3, were less than values measured after fetal T3 infusion. We conclude that T2S is a normal thyroid hormone metabolite in the ovine fetus and suggest that a major pathway of fetal T2S production is T3 to T3S to T2S.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Chromosome aberrations induced in human lymphocytes after partial-body irradiation.

Chromosomal aberrations in peripheral blood lymphocytes obtained from two patients before and after they received one fraction of partial-body irradiation for palliative treatment were analyzed. Blood samples were taken 30 min and 24 h after radiation treatment. The yield of dicentrics obtained from case A 30 min after a partial-body (about 21%) treatment with 8 Gy was 0.066/cell, while the yield obtained 24 h after radiation treatment was 0.071/cell. The fraction of irradiated lymphocytes that reached metaphase at 52 h was 0.08 as evaluated by mixing cultures of in vitro irradiated and unirradiated blood. The yield of dicentrics for blood from case B 30 min after 6 Gy partial-body (about 24%) irradiation was 0.655/cell, while the yield 24 h after irradiation was 0.605/cell. The fraction of irradiated cells was 0.29. Estimation of doses and irradiated fractions for the two cases using the method proposed by Dolphin and the Qdr method is discussed. Although there was no significant difference between the mean yields of dicentrics per cell obtained 30 min and 24 h after radiation treatment, the data obtained at 24 h seemed more useful for the purpose of dose estimation. When a higher dose (8 Gy) was delivered to a smaller percentage of the body, underestimation of the dose was encountered.

Aged

[Pharmacokinetics and bioavailability of glipizide capsules].

The pharmacokinetics and bioavailability of glipizide were studied in 8 healthy male volunteers after a single oral dose of 5 mg in capsule or in tablet. The plasma levels of glipizide were assayed by high performance liquid chromatography. The concentration--time curves of both preparations were fitted to a one compartment model. The pharmacokinetic parameters of glipizide in capsule and in tablet were shown in tables 2 and 3. The relative bioavailability of the capsule was 109.9% compared with the tablet.

Adult

Establishment of the sulfated 3,3'-diiodothyronine radioimmunoassay and its application in pregnant women.

Sulfation of iodothyronines is a major alternate pathway of thyroid hormone metabolism during fetal development. Sulfated 3,3'-diiodothyronine (T2S) is a low end metabolite of this pathway. Its clinical implications in the prenatal evaluation of fetal thyroid disorders are now being intensively investigated. A highly sensitive and reproducible radioimmunoassay (RIA) for T2S has been established in our laboratory. The detection threshold of the RIA approximated 5 pg T2S. The dose-response curve of T2S was essentially linear between 5-200 pg. An essentially parallel correlation of the dose-response curves for inhibition of binding of radiolabeled T2S and T2S antiserum was found between serial dilutions of serum extracts and the standards. The average intra- and inter-assay coefficients of variation were 7% and 15%, respectively. By applying the T2S RIA, we found that serum titers of T2S in pregnant women increased proportionately to the gestational age (first trimester vs. second trimester vs. third trimester: 30.1 +/- 1.4 vs. 41.6 +/- 1.9 vs. 98.0 +/- 3.9 ng/dL; p < 0.001 each). A high concentration of T2S was detected in cord and maternal serum at birth as compared to the results for non-pregnant women (165.1 +/- 10.3 vs. 113.7 +/- 5.6 vs. 7.5 +/- 0.9 ng/dL). The T2S levels decreased remarkably in maternal circulation 10 days after partuition. Four pregnant women who had two blood samplings four or more weeks apart during the third trimester showed invariable increases of serum T2S titers at later sampling times. Additionally, in the case of a pregnant woman who received two doses of T4 injections (200 micrograms/wk) intraamniotically for a previous Cretin birth, the maternal serum levels of T2S increased promptly from 47 ng/dL [corrected] to 96 ng/dL. Our findings imply that the established T2S RIA is clinically applicable, provide further evidence that the coincident increase of serum T2S titers in pregnant women may reflect ontogenesis of fetal thyroid hormone maturation, and provide a clue to the fetal thyroid status in the prenatal stage. However, more knowledge is still needed regarding the transfer and transformation of sulfated iodothyronine(s) from the fetal compartment to maternal circulation.

Analysis of Variance

Endothelin-1 inhibits insulin-stimulated glucose uptake in isolated rat adipocytes.

A single class of high affinity endothelin-1 (ET-1) binding sites with an apparent Kd of 350 pM and a binding capacity of 69,000 sites/cell was found in isolated rat adipocytes. Whereas ET-1 had no effect on basal glucose uptake, it inhibited insulin-stimulated glucose uptake in both a dose- and time-dependent manner. Insulin binding, however, was not altered. Thus, the present study demonstrates the presence of ET-1 receptor in isolated rat adipocytes and the inhibition of insulin-stimulated glucose uptake by ET-1 via a post-receptor mechanism.

Adipocytes

Early detection of unilateral occlusion of duplicated müllerian ducts: the use of serial pelvic sonography for girls with renal agenesis.

For early detection of unilateral occlusion of duplicated müllerian ducts, serial pelvic sonography was performed in 215 girls with known renal agenesis, especially following menarche, during the last 6 years. To date, 16 girls with unilateral occlusion of duplicated müllerian ducts were detected. We stress the value of this modality, which can lead to a prompt diagnosis, and allow for early and appropriate surgical intervention.

Abnormalities, Multiple

A 3,3'-diiodothyronine sulfate cross-reactive compound in serum from pregnant women.

Recently, we found high serum/urine concentrations of 3,3'-diiodothyronine sulfate (T2S) in both fetal and maternal sheep. In the present study, a RIA was employed to detect and measure serum T2S in women of different gestational ages and after delivery. Results were compared with values in nonpregnant women. In maternal serum, we identified a material that cross-reacts with T2S antibody, but is not T2S. Its concentration increased with the progression of pregnancy. The exact chemical structure of the T2S-like material (which we designated compound W) is unclear. It is immunologically (or chemically) similar to T2S, but does not cochromatograph with synthetic T2S in high pressure liquid chromatography. The serum concentrations of compound W were expressed as T2S equivalents (nanomoles per L +/- SE). Serum compound W concentrations were slightly elevated in women during the first trimester compared to those in nonpregnant women (0.73 +/- 0.04 vs. 0.17 +/- 0.02 nmol/L; P < 0.01). There was a moderate and progressive rise in the compound W concentration between 14-35 weeks gestation. The maternal serum compound W concentration then rapidly peaked before parturition (36-40 weeks gestation, 3.49 +/- 0.49 nmol/L; 27-35 weeks, 1.67 +/- 0.11 nmol/L; P < 0.01). After parturition, maternal serum levels of compound W decreased from 2.61 +/- 0.18 nmol/L (n = 25) to 1.47 +/- 0.12 nmol/L (n = 18) at 1 day, 0.89 +/- 0.07 nmol/L (n = 15) at 3 days, and 0.33 +/- 0.03 nmol/L (n = 8) at 7 days. hCG increased serum concentrations of T2S-cross-reactive material 6.2-fold (P < 0.01) in nonpregnant women. In summary, whereas hCG stimulation may account for some increase in maternal serum concentrations of this T2S-like material in the first trimester, the more rapid increase in maternal serum compound W concentrations during the late third trimester are probably related to changes that occur in fetal thyroid hormone economy. It is speculated that placental transfer and transformation of fetal T3 may be related to the rise in the level of T2S-like compound W in the serum of pregnant women.

Adolescent

Atrial demand pacing in patients with symptomatic sick sinus syndrome.

Atrial demand pacing provides a physiological, simply implemented, and less costly alternative of cardiac stimulation in symptomatic sick sinus syndrome (SSS) patients. Hindrance from widespread use stems mainly from the potential development of high degree AV block and persistent atrial fibrillation. A reappraisal of atrial pacing is now justified as we gain more clinical information. In this study we examined retrospectively the clinical course of 22 well-selected SSS patients paced in AAI mode for 30 +/- 29 months. Two patients had infrequent short-run atrial tachyrhythmia before implantation. There was an early lead dislodgement which required repositioning later. Three acute threshold increments were noted which necessitated a change in atrial pacing site in one and short-term steroid use in the other two. No other sensing, pacing or operative complication occurred and all pacing systems performed well. AII patients survived during follow-up and no patient developed congestive heart failure, though depressed left ventricular function was found in three preoperatively. No high degree AV block was encountered. Four patients presented paroxysmal atrial fibrillation (PAF) 25 +/- 16 months after the procedure, of whom one developed chronic atrial fibrillation. No single factor predicted the development of PAF. Resumption of normal pacemaker function always occurred immediately in the pause following cessation of PAF and no revision of pacing mode was required in the patient with chronic AF. Symptomatic relief was obtained in all patients. In summary, single chamber, single rate atrial pacing remains a physiologic, reliable, economic and easily implemented pacing modality affordable to a number of sick sinus patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Significance of acceleration period in a dynamic strength testing study.

The acceleration period that occurs during isokinetic tests may provide valuable information regarding neuromuscular readiness to produce maximal contraction. The purpose of this study was to collect the normative data of acceleration time during isokinetic knee testing, to calculate the acceleration work (Wacc), and to determine the errors (ERexp, ERwork, ERpower) due to ignoring Wacc during explosiveness, total work, and average power measurements. Seven male and 13 female subjects attended the test by using the Cybex 325 system and electronic stroboscope machine for 10 testing speeds (30-300 degrees/sec). A three-way ANOVA was used to assess gender, direction, and speed factors on acceleration time, Wacc, and errors. The results indicated that acceleration time was significantly affected by speed and direction; Wacc and ERexp by speed, direction, and gender; and ERwork and ERpower by speed and gender. The errors appeared to increase when testing the female subjects, during the knee flexion test, or when speed increased. To increase validity in clinical testing, it is important to consider the acceleration phase effect, especially in higher velocity isokinetic testing or for weaker muscle groups.

Acceleration

Therapeutic drug monitoring can avoid iatrogenic alterations caused by 99mTc-methylene diphosphonate (MDP)-gentamicin interaction.

Gentamicin is an aminoglycoside antibiotic used to treat a wide variety of infections caused by gram-negative organisms, but it is potentially toxic to the kidneys. Due to its nephrotoxicity, gentamicin may cause abnormal renal uptake to be seen on 99mTc-MDP bone scintigraphy. The presence of the radiopharmaceutical in the kidneys, along with an increase in renal retention, tend to produce scintigraphic results that falsely identify characteristics related to diseases such as renal vascular, or urinary tract obstruction, and even renal cancer. An altered biodistribution may provide misleading information that can either mask or mimic certain disease symptoms. A method to maximize the therapeutic benefit of gentamicin while minimizing the risk of nephrotoxicity and the appearance of a hot kidney on scintigraphy is desirable. Serial pharmacokinetic dosing has been proposed as a method to accomplish this goal. Therapeutic drug monitoring (TDM) of gentamicin therapy, and bone scintigraphy employing 99mTc-MDP as the radiopharmaceutical was carried out in 22 patients. The data presented here demonstrate that with serial pharmacokinetic dosing of gentamicin, the iatrogenic alteration caused by gentamicin therapy can be avoided.

Bone and Bones

The development of a radioimmunoassay for reverse triiodothyronine sulfate in human serum and amniotic fluid.

Sulfated iodothyronines including T4-sulfate (T4S) and T3-sulfate (T3S) have been identified in human serum and amniotic fluid. Little is known, however, about the existence of sulfate conjugation of reverse T3 (rT3S) in man. In this report, we employed a novel, sensitive, and specific rT3S RIA to address this question. The rabbit antiserum to rT3S was highly specific; T4, T3, rT3, and 3,3'-T2 showed less than 0.002% cross-reaction with the antiserum. Only T4S and T3S cross-reacted significantly (0.3% and 0.01%, respectively); other analogs cross-reacted less than 0.0001%. The detection threshold of the RIA was 14 pmol/L (1.0 ng/dL). The mean serum rT3S concentration (pmol/L) was 40 in euthyroid subjects. Values were similar in hypothyroid patients (38) and pregnant women (52) but significantly (P < 0.01) elevated to 176 in hyperthyroid patient, 74 in patients with nonthyroid illnesses, and 684 in cord sera of newborns. Serum rT3S increased significantly in hyperthyroid patients 1 day after administration of 1 g sodium ipodate orally. Reverse T3S was detected consistently in amniotic fluid at 14 to 22 weeks of gestation and showed a marked rise 1-3 weeks after intraamniotic administration of 500-1000 micrograms T4. The various data suggest that: (1) rT3S is a normal component of human serum and amniotic fluid; (2) it is derived from metabolism of T4 or rT3; (3) circulating rT3S increases in hyperthyroidism and in circumstances where type I 5'-monodeiodinating activity is low, e.g. nonthyroid illnesses, fetal life, and after administration of ipodate.

Amniotic Fluid

Radioiodine I-131 therapy in the management of differentiated thyroid carcinoma: a review of 202 patients.

During the 13-year period from 1978 to 1991, 202 patients with differentiated thyroid carcinoma were treated with radioactive iodine-131 (I-131) post-operatively. The therapeutic response and survival rates were studied. Of these patients, 172 (85%) patients were shown to be totally disease-free; others showed a partial response or persistence of disease. A total of 134 patients (66%) achieved total thyroid ablation with only one therapeutic dose of I-131, ranging from 100-200 mCi. Patients over the age of 40 years at the time of diagnosis had a lower survival rate than those under 40 years old (98.6% vs 68.9%; p < 0.001). However, patients over the age of 50 years and follicular patients had a lower recurrence rate than patients under the age of 50 years and those with papillary carcinoma. Eight of the 32 patients (25%) with lung metastases were detected by a therapeutic I-131 whole body scan (WBS), in which the diagnostic I-131 WBS was negative. In six of the 16 patients (37.5%) with bony metastases, the I-131 WBS showed more obvious positive results than the Tc-99m methylene diphosphonate (MDP) bone scanning. Most of the remaining patients exhibited the same findings for the two methods. Therefore, I-131 WBS is superior to Tc-99m MDP bone scanning in the detection of bony metastases from thyroid carcinoma. The mortality rate of patients with bony metastases was four times that of patients with lung metastases (40% vs 10%). Patients with follicular carcinoma had higher rates of distant metastases than those with papillary carcinoma (13% vs 4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Follicular