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Biomedical subjects

T C Chang

Publications and source records attributed to T C Chang.

At least 145 records · Page 8Linked to original sources

Linear growth response to recombinant human growth hormone in children with growth hormone deficiency.

BACKGROUND: This study was to evaluate the efficacy, safety and immunogenicity of recombinant human growth hormone (rhGH) in treatment of children with growth hormone deficiency (GHD). METHODS: We selected 15 children with GHD for a 12-month clinical trial and separated them into three groups with each 5 patients receiving one of the 3 tested rhGH (Saizen by Serono, Aubonne, Switzerland; Genotropin by KabiVitrum, Stockholm, Sweden and Humatrope by Eli Lilly, Indianapolis, USA). RESULTS: In Saizen group, 3 boys and 2 girls with a mean chronological age (CA) of 10.6 +/- 1.7 yrs and bone age (BA) of 6.7 +/- 1.2 yrs, at dose of 0.2 IU/kg sc tiw, gained an average BA of 2.1 +/- 1.3 yrs. The mean height velocity (HV) increased from 3.7 +/- 1.2 to 11.1 +/- 3.3 cm/yr. The height standard deviation score (SDS) increased from -4.2 +/- 3.1 to -3.1 +/- 2.9. In Genotropin group, 2 boys and 3 girls with a mean CA of 9.2 +/- 2.3 yrs and BA of 5.6 +/- 2.1 yrs, at dose of 0.1 IU/kg sc qd, gained an average BA of 0.8 +/- 0.2 yr. The mean HV increased from 3.4 +/- 0.7 to 11.3 +/- 2.0 cm/yr. The height SDS increased from -4.0 +/- 0.5 to -2.7 +/- 0.7. In Humatrope group, 4 boys and 1 girl with a mean CA of 10.3 +/- 3.5 yrs and BA of 5.8 +/- 2.9 yrs, at dose of 0.1 IU/kg sc qd, gained at average BA of 0.8 +/- 0.7 yr. The mean HV increased from 4.0 +/- 1.3 to 9.4 +/- 1.9 cm2yr, and the height SDS increased from -2.9 +/- 0.7 to -2.2 +/- 1.0. Very low titers of anti-rhGH antibodies were noted only in two patients, one in Saizen group (titer = 1:10) and the other in Genotropin group (titer = 1:6). Their HV was not affected (Saizen: 13.3 cm/yr, Genotropin: 11.2 cm/yr). One patient evolved subclinical hypothyroidism whereas no side effect at all was noted in the rest of patients. CONCLUSIONS: Three tested GH (Saizen, Genotropin, Humatrope) produced by recombinant DNA technology appear to make no significant difference in this clinical trial, and rhGH therapy is an effective and safe treatment for prepubertal GHD children.

Adolescent↗

Neonatal morphometric indices of fetal growth: analysis of observer variability.

Measurements of triceps and subscapular skinfold thickness, mid-arm circumference (MAC), head circumference (HC) and crown-heel length were performed by two observers in 30 healthy neonates. Intra-observer standard deviation for all measurements, calculated using one-way analysis of variance, was small and similar for each observer. Inter-observer variability was assessed using limits of agreement. There were small, systematic, differences between observers for measurements of triceps skinfold thickness and crown-heel length, and for calculated ponderal index (PI). When related to respective published reference ranges, the 95% prediction intervals for subscapular (-0.51, 0.68 mm) and triceps (-0.65, 0.29 mm) skinfold thicknesses were less than those for the MAC/HC ratio (-2.1, 1.9) and PI (-0.23, 0.28). The results indicate that skinfold thickness measurements are a more robust measure and, therefore, may be of greater value in the assessment of neonates with suspected fetal growth retardation.

Anthropometry↗

Uteroplacental resistance index: analysis of intra- and interobserver variability.

The aim of this study was to assess the intra- and interobserver variability of second-trimester uteroplacental continuous-wave flow velocity waveforms. The left and right uterine and arcuate resistance indices were measured in women having their routine booking scan at 16-24 weeks' gestation. Four experiments assessed the intra-observer between-frame variability, the intraobserver beat-to-beat variability, the intraobserver temporal variability, and the interobserver variability, using the limits-of-agreement method. The intraobserver between-frame variability was greater than the beat-to-beat variability at three of the four sites. The temporal variability was not significantly different between sites. There were wide interobserver limits of agreement with respect to the reference ranges, although they were greater at arcuate sites than uterine sites. These observations suggest that the reproducibility of the resistance index in continuous wave Doppler uteroplacental flow velocity waveforms is poor, particularly from arcuate sites. The uterine site is preferable and descriptive analysis may be better.

Journal Article↗

Immobilization of the tetrameric and monomeric forms of pigeon liver malic enzyme on Sepharose beads.

Pigeon liver malic enzyme was chemically attached to Sepharose 4B-CL beads. The enzyme lost approximately 50% of its original activity when immobilization was carried out with 5 mg CNBr/ml gel. Immobilization performed at pH 8.0 or pH 4.5 resulted in the formation of matrix-bound tetramer and monomer, respectively. Matrix-bound reconstituted tetramer was derived from matrix-bound monomer by mixing the latter with soluble enzyme at pH 4.5, then raised the pH of the solution to 8.0. The matrix-bound monomer was demonstrated to be enzymically fully active in terms of specific activity. The pH profile for the enzymic reaction was similar for both soluble and immobilized enzymes. However, the latter had a broader range for the optimum pH (pH 6.8-7.8). The Arrhenius plots for all immobilized enzyme forms were biphasic with inflection at approximately 27 degrees C. The apparent Michaelis constants for the substrates increased about 2-3-fold after immobilization. All immobilized enzyme forms, including the matrix-bound monomer, showed substrate inhibition at high concentrations of L-malate. Both high-affinity and low-affinity binding sites for Mn2+ existed for all immobilized enzyme forms. These results are consistent with an existing asymmetric model, but are not compatible with a sequential model for the enzyme tetramer. The immobilized enzyme was stable for at least four months at 4 degrees C. As compared to soluble enzyme, the immobilized enzyme was less inhibited by (NH4)2SO4 or NaCl. It was also resistant to inactivation with periodate-oxidized aminopyridine adenine dinucleotide phosphate, an affinity label for malic enzyme. Incubation of the immobilized enzyme (1.25 microM) with the reagent (5.6 mM) resulted in pseudo-first-order inactivation with a rate constant of 0.0108 min-1 that was at least an order of magnitude smaller than that for the soluble enzyme.

Animals↗

An investigation of fetal growth using serial ultrasound data.

Serial ultrasonic measurements were performed in 67 Caucasian fetuses from 20 weeks' gestation until term to derive reference standards for abdominal circumference (AC) and estimated fetal weight (EFW). The variances of both AC and EFW increased with gestational age. Four mathematical models (linear, quadratic, Gompertz and Rossavik) were fitted to the log(10)(AC) and log(10)(EFW) data from each fetus using least squares regression analysis. The standard deviations of the residual error were greatest for the linear model. The linear model also overestimated the final log(10)(AC) while the linear, Gompertz and Rossavik models all overestimated the final log(10)(EFW) when these data were omitted from the fitting process. The individual quadratic constants were, therefore, used to produce 67 individual growth curves. Values of log(10)(AC) and log(10)(EFW) for each fetus at exact gestational ages between 20 and 40 weeks were derived by interpolation; the mean and standard deviation values were then used to derive centile ranges for abdominal circumference and estimated fetal weight. These standards should prove useful in the assessment of fetal growth.

Journal Article↗

Ultrasonic fetal weight estimation: analysis of inter- and intra-observer variability.

Standard ultrasound measurements were performed by two observers in 40 third-trimester fetuses. Observers were blinded to the results of the measurements. Estimated fetal weight (EFW) was calculated using two published formulae. The intra-observer standard deviation for EFW, assessed using one-way analysis of variance, was < 75 g for both observers. The 95% prediction intervals for inter-observer comparisons of EFW, calculated using the limits of agreement method, were -187.3 g to 139.8 g, and -159.9 g to 124.3 g, using the two formulae. The results suggest that measurements of EFW are reproducible. The prediction interval is comparable to the weekly fetal weight increment in normal fetuses.

Analysis of Variance↗

Prognostic factors and impacts of adjuvant therapy in early-stage cervical carcinoma with pelvic node metastases.

Three hundred seventy cases of clinical stage Ib-II cervical carcinoma treated with radical abdominal hysterectomy and bilateral pelvic lymphadenectomy at Chang Gung Memorial Hospital between 1981-1986 were reviewed retrospectively. Of these, 105 patients had pelvic lymph node metastases. Clinicopathological variables including flow cytometric DNA analysis and the use of adjuvant therapy were studied. Recurrence-free survival was significantly worse among patients with positive pelvic nodes by parametrial extension, increasing number of positive nodes, and DNA index greater than 1.3. In patients with positive nodes and negative parametria, the number of positive nodes remained a significant predictor of survival. Utilizing these significant variables, we identified three distinct risk groups. Those patients who had negative parametria, only one positive node, and a DNA index not greater than 1.3 were categorized as the low-risk group. Those who had either positive parametria or more than three positive nodes were categorized as the high-risk group. All the others fell into the intermediate-risk group. Five-year recurrence-free survival rates were 84.6, 71.6, and 42.1%, respectively (P = 0.0006). Applying this risk group classification and the significant risk factors, we may select more appropriate subsets of patients and good stratification for future prospective trials in surgically treated early-stage cervical carcinoma patients with pelvic node metastases.

Antineoplastic Agents↗

Thyroid disorders in Chinese patients with systemic lupus erythematosus.

To clarify the prevalence of thyroid disorders in Chinese patients with systemic lupus erythematosus (SLE), 45 SLE patients not receiving corticosteroid therapy for at least 6 months were selected over a period of 1 year. They were investigated by utilizing thyroid ultrasonography and by determinations of thyroid antibodies and thyroid function. Of these patients, 24 (53.3%) showed abnormal sonographic findings. Thyroid antibodies (microsomal and/or thyroglobulin) were detected in 21 patients (46.7%), but a low index of thyrotropin-binding inhibitory immunoglobulin (TBII) was found in only one euthyroid patients with a normal echogram. Ten patients (22.2%) had abnormal thyroid function. The mean disease duration was longer in patients with thyroid anomalies (p < 0.05). Hashimoto's thyroiditis was found in four patients (8.8%), two of whom had hypothyroidism. We concluded that thyroid anomalies are frequently found in patients with SLE in the area of this study. The possibility of the coexistence of thyroid disorders in systemic lupus erythematosus should be carefully considered throughout the course of patients' follow-up, especially in those with a long disease duration.

Adult↗

Glutathione concentration and distribution in cervical cancers and adjacent normal tissues.

Intracellular glutathione (GSH) has been shown to play an important role in modulating the cellular response to many cytotoxic agents, including radiation and chemotherapeutic drugs. In this study, individual glutathione levels from contiguous blocks of cervical cancer tissue were determined in order to investigate the intratumor GSH distribution and variation, as well as the difference between tumor and its normal counterpart. The GSH content of a squamous cell carcinoma of the cervix was twofold higher than its normal counterpart, but there was no obvious difference in a case with adenoid cystic carcinoma. The tumor margin adjacent to normal tissue has a higher GSH content than the tumor center in a large tumor. Although the intertumor variation in GSH is different in these two tumors, a common coefficient of variation, 26, is observed, which may be used to estimate the range of tumor GSH if it can only be determined by a biopsy.

Carcinoma, Adenoid Cystic↗

Pentoxifylline inhibits the proliferation and glycosaminoglycan synthesis of cultured fibroblasts derived from patients with Graves' ophthalmopathy and pretibial myxoedema.

Excessive amounts of glycosaminoglycans accumulate in the extraocular muscles of patients with Graves' ophthalmopathy and in the affected skin of patients with pretibial myxoedema. It is widely accepted that fibroblasts are the sources of glycosaminoglycan synthesis. Pentoxifylline, an analogue of the methylxanthine theobromine, inhibits the proliferation and certain biosynthetic activities of fibroblasts derived from normal human skin and from skin of patients with some fibrotic disorders. Our objective was to determine whether pentoxifylline has similar effects on fibroblasts derived from patients with Graves' ophthalmopathy and pretibial myxoedema and could serve as a candidate for the treatment of these manifestations. Fibroblasts from the extraocular muscles of two patients with Graves' ophthalmopathy and normal extraocular muscles of two subjects with strabismus, as well as the affected skin of two patients with pretibial myxoedema were cultured in vitro in the presence and absence of pentoxifylline to assay its effect on the proliferation of fibroblasts and their production of glycosaminoglycans. In subconfluent fibroblast cultures, pentoxifylline treatment caused a dose-dependent inhibition of serum-driven fibroblast proliferation. In confluent fibroblast cultures both in the presence and absence of serum, exposure to pentoxifylline similarly resulted in a dose-dependent inhibition of glycosaminoglycan synthesis for all these different kinds of fibroblasts. These findings may form the rationale for a clinical trial using pentoxifylline for the treatment of Graves' ophthalmopathy and pretibial myxoedema.

Adult↗

Nesidiodysplasia: an unusual cause of hyperinsulinemic hypoglycemia in adults.

Herein, we report two cases of pancreatic nesidiodysplasia, an extremely rare cause of hyperinsulinemic hypoglycemia in adults. The first case was a 43-year-old, nonobese female with recurrent hypoglycemia after 10% distal pancreatectomy with splenectomy performed 16 years previously for insulinoma. Three suspect tumors were found on the preoperative angiograms and second operation, but the pathologic finding revealed diffusely scattered microscopic nodules with a background of nesidiodysplasia. The second case was a 52-year-old female with a five-year history of hypoglycemia. Extensive diagnostic procedures revealed a suspect insulinoma over the pancreatic body. The histology confirmed diffuse nesidiodysplasia. Both cases were diagnosed as insulinoma before surgical intervention because of the hypoglycemic symptoms, high insulin/glucose ratio and the positive image studies. The pathologic findings were characterized by the budding of islet cells from the pancreatic duct epithelium with diffuse islet hyperplasia. Both patients remained well after 75% to 80% pancreatectomy with no recurrence of hypoglycemia. The etiology, pathology, preoperative work-up, and operative strategy of nesidiodysplasia are discussed.

Adult↗

Identification of fetal growth retardation: comparison of Doppler waveform indices and serial ultrasound measurements of abdominal circumference and fetal weight.

OBJECTIVE: To compare the serial ultrasound assessment of abdominal circumference (AC) and fetal weight versus single values of umbilical artery pulsatility index (PI) and the aortic-middle cerebral PI ratio in the identification of fetal growth retardation (FGR). METHODS: Serial AC measurements and estimates of weight were obtained in 104 small fetuses in the third trimester of pregnancy. These serial values (expressed as a change in standard deviation [SD] scores) were compared with the final value of AC and estimated fetal weight (EFW), umbilical artery PI, and the aortic-middle cerebral artery PI ratio (all expressed as SD scores) for their ability to predict a reduced neonatal ponderal index, mid-arm circumference-head circumference (HC) ratio, and skinfold thickness. Receiver-operating characteristic (ROC) curves were derived and the ultrasound measurements evaluated by calculating the areas under the ROC curves. RESULTS: Serial estimates of fetal weight resulted in a significantly larger area under the ROC curve compared with the final aortic-middle cerebral PI ratio in the prediction of an abnormal mid-arm circumference-HC ratio and compared with the final AC, EFW, and umbilical artery PI in the prediction of all neonatal morphometric indices. CONCLUSION: In small fetuses, fetal growth failure as determined by the serial assessment of AC and EFW was superior to the final AC and EFW, umbilical artery PI, and the aortic-middle cerebral PI ratio in the prediction of abnormal neonatal morphometry indicative of FGR.

Adult↗

Human placental alkaline phosphatase. An improved purification procedure and kinetic studies.

An improved method for the purification of human placental alkaline phosphatase is described. The partially purified enzyme from Sigma was further purified by successive Concanavalin A-Sepharose and Q-Sepharose chromatography. The whole procedure may be completed in one working day. Highly purified enzyme was obtained with a 39% yield. The intrinsic fluorescence of the enzyme decreased at elevated temperature. The conformation of the enzyme molecule was studied by the fluorescence quenching technique. Upward Stern-Volmer plots were obtained for the quenching data which suggested that, in addition to collisional quenching, static quenching was involved in the quenching mechanism. The dynamic and static quenching constants were found to be 0.7 +/- 0.16 M-1 and 0.44 +/- 0.1 M-1, respectively, using acrylamide as the quenching agent. The corresponding values were 0.43 +/- 0.23 M-1 and 0.84 +/- 0.18 M-1, respectively, with KI as the quenching agent. Mg2+ and PO4(3-) induced protein conformational changes which altered both the dynamic and static quenching constants. Mg2+ was found to be a non-essential activator for the placental alkaline-phosphatase-catalyzed hydrolysis of 4-nitrophenyl phosphate. At pH 9.8, Mg2+ increased Vmax by 1.2-fold without affecting the Kd of the substrate. The tetranitromethane-modified enzyme showed slower migration toward the anode on electrophoresis and increased Kd for Mg2+.

Alkaline Phosphatase↗

Protein classification artificial neural system.

A neural network classification method is developed as an alternative approach to the large database search/organization problem. The system, termed Protein Classification Artificial Neural System (ProCANS), has been implemented on a Cray supercomputer for rapid superfamily classification of unknown proteins based on the information content of the neural interconnections. The system employs an n-gram hashing function that is similar to the k-tuple method for sequence encoding. A collection of modular back-propagation networks is used to store the large amount of sequence patterns. The system has been trained and tested with the first 2,148 of the 8,309 entries of the annotated Protein Identification Resource protein sequence database (release 29). The entries included the electron transfer proteins and the six enzyme groups (oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases), with a total of 620 superfamilies. After a total training time of seven Cray central processing unit (CPU) hours, the system has reached a predictive accuracy of 90%. The classification is fast (i.e., 0.1 Cray CPU second per sequence), as it only involves a forward-feeding through the networks. The classification time on a full-scale system embedded with all known superfamilies is estimated to be within 1 CPU second. Although the training time will grow linearly with the number of entries, the classification time is expected to remain low even if there is a 10-100-fold increase of sequence entries. The neural database, which consists of a set of weight matrices of the networks, together with the ProCANS software, can be ported to other computers and made available to the genome community. The rapid and accurate superfamily classification would be valuable to the organization of protein sequence databases and to the gene recognition in large sequencing projects.

Computers, Mainframe↗

Neoadjuvant chemotherapy with cisplatin, vincristine, and bleomycin and radical surgery in early-stage bulky cervical carcinoma.

Neoadjuvant chemotherapy consisting of 2-3 courses of cisplatin, vincristine, and bleomycin was used in the primary treatment of 36 consecutive patients with locally advanced early-stage cervical carcinoma [International Federation of Gynecology and Obstetrics (FIGO) stages Ib or IIa; tumor size, greater than or equal to 4 cm]. The effectiveness of the preoperative chemotherapy was evaluated in the surgical specimens. Among the 33 evaluable patients, the overall clinical response rate was 84.8%, which included a complete response in 8 patients (24.2%) and a partial response in 20 subjects (60.6%). No residual tumor was found in the surgical specimens obtained from 2 complete responders. This therapy induced varying degrees of tumor shrinkage and rendered radical surgery feasible in all evaluable cases despite the initial bulky size of the lesions. No significant difference was observed in the response rate according to age and disease stage. Lymph-node metastases were found after chemotherapy in 18.2% (6/33) of the patients. Grade II and III hematological toxicities occurred in 23.3% of the 90 chemotherapy cycles completed. Nausea and vomiting occurred to a mild to moderate degree in 75 (83.3%) cycles. These preliminary results suggest that the administration of induction chemotherapy involving two to three courses of cisplatin, vincristine, and bleomycin prior to surgery is effective in reducing the tumor volume and in providing better circumstances for surgical removal of the early yet bulky cervical tumors and results in tolerable toxicity. This protocol is now undergoing prospective randomized trials to test its impact on long-term survival.

Adult↗