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Biomedical subjects

M J Huang

Publications and source records attributed to M J Huang.

At least 37 records · Page 2Linked to original sources
PubMed1998

Papillary and follicular thyroid carcinomas with bone metastases: a series of 39 cases during a period of 18 years.

BACKGROUND: Bone metastases can cause death in patients with papillary or follicular thyroid carcinoma. There is, however, limited information about the clinical presentations and prognoses of patients with papillary and follicular thyroid carcinomas with bone metastases in Taiwan. MATERIALS AND METHODS: A series of 39 patients with papillary or follicular thyroid carcinomas with bone metastases treated at our center from 1977 through 1995 was retrospectively reviewed to elucidate the clinical presentations and results of treatment of this disease. RESULTS: The occurrence rate of bone metastasis in papillary and follicular thyroid carcinomas was 4.3%. Of the 39 patients, whose mean age was 57.5 years, 28 (71.8%) had follicular and 11 (28.2%) had papillary carcinomas. Thirty-two patients (82.1%) were female and 7 (17.9%) were male. Twenty-nine patients (74.4%) presented with bone metastases before the thyroid cancers were diagnosed. Bone metastases were detected using radiography in 33 patients and using 131I scans in 28 patients. Thirty-one patients (79.5%) had multiple bone metastases. The spine was the most frequently involved site (53.8%). Three patients were disease-free and 14 patients died during the course of treatment. Using the Kaplan-Meier method, the 5-year survival rate was estimated to be 64.9%. CONCLUSION: Bone metastasis, although rare in patients with papillary carcinoma, was not very uncommon in patients with follicular carcinoma. Bone metastases occurred more often in older patients. Multiple bone metastases were noted more often than single bone metastasis. Most patients had symptoms and signs resulting from metastatic bone lesions. Although multimodality therapy was tried, the prognoses for most patients with bone metastases were poor.

Adenocarcinoma, Follicular↗
PubMed1997

Results of external beam radiotherapy in patients with well differentiated thyroid carcinoma.

Surgical, thyroid hormone and radioactive 131I therapy are the standard curative treatments for well differentiated thyroid cancer. However, for residual, recurrent and nodal involvement of well differentiated thyroid cancer, external radiotherapy may be important in preventing distant metastases. The postoperative treatment of well differentiated human thyroid cancer with external radiotherapy is controversial. We retrospectively reviewed the records of 699 patients with papillary or follicular thyroid cancer, of whom 72 received external radiotherapy treatment after surgery. Thirty-two of these patients were at clinical stage 2 or 3 at the time of diagnosis while 172 patients at clinical stages 2 or 3 did not receive external radiotherapy after surgery. The patients who received external radiotherapy were older than those who did not (42.9 +/- 14.5 vs. 38.6 +/- 15.3), although this was not statistically significant. There were no significant differences in clinical parameters including surgical methods employed, histopathological types of cancer, follow-up stages, postoperative thyroglobulin levels, tumor size, accumulated 131I doses and survival rates between the two groups. To clarify the effect of external radiotherapy in patients with local invasion, we compared the survival rates of the patients with clinical stage 3 in the two groups and again no significant difference was found. During the follow-up period, 21 (28.4%) of the 72 patients who received external radiotherapy died of thyroid carcinoma. In our limited period of study, external radiotherapy did not improve the survival rate of patients with well differentiated thyroid cancer, though it appeared to cause temporary tumor regression.

Adenocarcinoma, Follicular↗
PubMed1997

Two novel glucose 6-phosphate dehydrogenase deficiency mutations and association of such mutations with F8C/G6PD haplotype in Chinese.

Glucose 6-phosphate dehydrogenase (G6PD) deficiency is a common genetic disease affecting 3% of the total Chinese population in Taiwan. To investigate the molecular basis of this deficiency, we analyzed blood samples from G6PD-deficient newborns using a nonradioactive polymerase chain reaction coupled with single-stranded conformation polymorphism (PCR-SSCP) analysis. We identified two novel G6PD mutations in Chinese. The first, G6PD Miaoli, involved a C-->G substitution at nucleotide (nt) 519, producing a Phe173 to Leu change in the protein. The second mutation (G6PD Keelung) involved a C-->T change at nt 1387, resulting in an Arg463 to Cys substitution. The F8C/G6PD (coagulation factor VIIIc) haplotype that spans the Xq28 region from the gene for coagulation factor VIIIc to the gene for G6PD was also investigated in Chinese using PCR and restriction enzyme digestion. Of the 16 possible haplotypes, only four were found, which suggests that these four polymorphic sites are in strong linkage disequilibrium. Analysis of the association of G6PD mutations with F8C/G6PD haplotype revealed that nt 517, 592, 835, and 1387 mutations are linked to haplotype VI+VII, whereas the nt 519 mutation is linked to haplotype III. The finding that some G6PD mutations are associated with a particular F8C/G6PD haplotype may be useful for future population studies.

Female↗
PubMed1996

Neonatal jaundice and molecular mutations in glucose-6-phosphate dehydrogenase deficient newborn infants.

Molecular mutations of the glucose-6-phosphate dehydrogenase (G6PD) gene and clinical manifestations of neonatal jaundice in 112 male and 50 female Chinese neonates with G6PD deficiency were studied. In the 112 males, the nucleotide (nt) 1376 (G-->T) mutation was the dominant type (50.0%), followed by nt 1388 (G-->A) (16.1%), nt 493 (A-->G) (8.0%), nt 1024 (C-->T) (6.2%), nt 95 (A-->G) (5.4%), nt 392 (G-->T) (1.8%), nt 487 (G-->A) (1.8%), nt 871 (G-->A) (0.9%), and nt 1360 (C-->T) (0.9%). The nt 871 variant has not been reported in Taiwan before. The occurrence rates for nt 1376, nt 1388, nt 493, nt 95, and nt 1024 mutations in the 50 females were 44.0%, 18.0%, 12.0%, 6.0%, and 6.0%, respectively. The type of G6PD mutation in 10 male and 7 female neonates has not been identified yet. Although G6PD deficient neonates had higher frequency of phototherapy than G6PD normal neonates in both sexes, a significant difference in the prevalence of hyperbilirubinemia (peak bilirubin > or = 15.0 mg/dl) between G6PD deficient and normal neonates was found only in males. Further analysis showed that duration of phototherapy was longer in G6PD deficient male neonates than in the control group, while the outcome of phototherapy was better in subjects with non-nt 1376 mutations than subjects with the nt 1376 mutation. Most (78.3%) of the 23 G6PD deficient neonates who subsequently suffered from neonatal hyperbilirubinemia carried the nt 1376 mutation. The results of this study indicate that the nucleotide substitution at 1376 is the most common and important mutation for G6PD deficiency in Chinese neonates in Taiwan.

Base Sequence↗
PubMed1996

The clinical significance of gall-bladder non-visualization in cholescintigraphy of patients with choledochal cysts.

Intravenous radionuclide cholescintigraphy (IVRC) provides a very specific picture for choledochal cysts. However, the clinical significance of the non-visualization of the gall-bladder (GB) activity in these cases is unclear. In this study, we reviewed 27 patients with choledochal cysts who underwent IVRC within 7 days prior to operation and correlated the GB findings on IVRC with the histopathological results. In 18 of the 27 patients (66.7%), there was non-visualization of the GB at 4 h post injection. Among these, two had histopathological features of acute cholecystitis (AC), 11 had chronic cholecystitis (CC), and five had normal GBs. In the other nine patients with visualization of the GB, there were five cases of CC and four normal GBs. If we apply the finding of non-visualization of the GB at 4 h post injection as the criterion for the diagnosis of AC, the diagnostic accuracy was only 40.7% (11/27). We concluded that: (1) GB disease (AC and CC) was common (66.7%: 7.4% and 59.3% respectively) in choledochal cyst patients. (2) Non-visualization of the GB on IVRC did not necessarily indicate AC in choledochal cyst cases, and the diagnostic accuracy was low. (3) GB disease is not the only cause of GB non-visualization on IVRC. A huge choledochal cyst causing a mass or reservoir effect may be a cause of GB compression and result in non-visualization of the GB.

Child↗
PubMed1996

Identification of malnutrition-related diabetes mellitus among hospitalized patients in Taiwan.

A retrospective review of 1,089 diabetes mellitus admitted to the metabolic ward of Chang Gung Memorial Hospital was performed to screen for malnutrition-related diabetes mellitus (MRDM). None of the patients fulfilled the MRDM criteria, although 20 patients with a body mass index < or = 15 kg/m2 were further analyzed. These patients presented with poor glycemic control and most had associated chronic diseases. C-peptide levels were < 0.8 ng/mL in 17 patients and undetectable in six patients. Two patients experienced diabetic ketoacidosis (DKA). Insulin treatment was required by 18 patients with a mean (+/- SD) dosage of 30 +/- 9 U/day. During follow-up of 14 of the patients for 9.8 +/- 4.3 months, HbA1c decreased significantly. Their mean body weight and body mass index increased significantly from 36.6 +/- 4.6 kg to 47.2 +/- 6.2 kg and 13.9 +/- 0.9 to 18.0 +/- 1.9 kg/m2, respectively. Careful attention should be paid to diabetic control and associated chronic illness in patients with severe undernutrition.

Adult↗
PubMed1996

Parathyroid carcinoma with postoperative prolonged hypocalcemia in a patient with chronic renal failure.

Parathyroid carcinoma is a rare disease that usually presents with severe hypercalcemia and marked elevation of parathyroid hormone level. A 64-year-old male patient with repeated episodes of renal stones sustained chronic renal failure. Subsequently, he developed acute uremic symptoms and underwent a left upper parathyroidectomy. Parathyroid carcinoma was diagnosed after surgery. Asymptomatic hypocalcemia was the initial presentation. Protracted symptomatic hypocalcemia developed 8 months postoperatively, accompanied by an extremely high parathyroid hormone level. Delayed "bone hunger" syndrome concomitant with down-regulation of the parathyroid hormone receptors or production of parathyroid hormone with diminished bioactivity may have been the possible causes.

Humans↗
PubMed1995

Efficacy of a 3-substituted versus 17-substituted chemical delivery system for estradiol brain targeting.

Brain-targeted delivery of estrogens has been achieved by a chemical delivery system (CDS) in which a molecular targetor (1-methyl-1,4-dihydronicotinate) was attached to the 17-alcohol of estradiol. Optimization of this effect was attempted with the isomeric 3-phenol ester. Estradiol 3-nicotinate was prepared with nicotinic anhydride, which selectively acylated the phenol position. Methylation and reduction gave estradiol 3-(1-methyl-1,4-dihydronicotinate) of the 3-E2-CDS. Theoretical and electrochemical investigation indicated that the 3-E2-CDS was more stable to oxidation than was the prototype 17-ester (17-E2-CDS). Systemic administration of the 17-E2-CDS produced high levels of the corresponding quaternary salt in the brain of rats, which disappeared with an estimated half-life of > 2 days, but 3-E2-CDS dosing resulted in no significant quaternary salt trapping. Pharmacological activity was potent and sustained after 17-E2-CDS dosing but transient after 3-E2-CDS administration. Thus, the 3-E2-CDS reduced the rate of weight gain in male rats but to a lesser extent and for a shorter duration than did the 17-E2-CDS. Similar effects were seen on pituitary hypertrophy, reduction in serum androgen concentrations, and involution of prostate and seminal vesicles. The results of these studies suggest that placement of the targeting ester at the phenol position increases dihydropyridine stability but, at the same time, reduces brain sequestration.

Animals↗
PubMed1995

Theoretical studies on the structures of natural and alkylated cyclodextrins.

A series of semiempirical molecular orbital calculations using the AM1 method have been performed on isolated natural and alkylated alpha- and beta-cyclodextrins. For natural cyclodextrins, three geometries were considered: (i) molecular mechanics (MM2); (ii) AM1 fully optimized geometry; (iii) X-ray structures based on the experimental coordinates for heavy atoms with positions of hydrogen atoms optimized by AM1. Large differences between AM1 calculated properties of geometries i-iii were found. The differences between ii and iii are smaller and reflect the intermolecular, crystal packing forces. Comparisons are made between ii and iii and properties determined therefrom, such as cavity diameter, outer diameter, and height. In addition, AM1 semiempirical calculations were performed on the mixed (2,3,6) (hydroxyprophyl)-beta-cyclodextrin, 2,6-dimethyl-beta-cyclodextrin, and 2,6-bis(hydroxypropyl)-beta-cyclodextrin. The results were compared with the substituent effects on monoglucose. It was found that the alkylation and methyl and 2-(hydroxypropyl) functions on beta-cyclodextrin does not introduce significant steric hindrance.

Alkylation↗
PubMed1995

Preparation, characterization, and anesthetic properties of 2-hydroxypropyl-beta-cyclodextrin complexes of pregnanolone and pregnenolone in rat and mouse.

Prototype formulations of the progesterone derivatives pregnanolone and pregnenolone were prepared by solubilizing the steroids in 2-hydroxypropyl-beta-cyclodextrin (HP beta CD). The aqueous solubility of the steroids was increased as a function of HP beta CD concentration generating linear (AL) or curvilinear (AP) phase-solubility profiles. While the solubility of pregnanolone could not be increased with the addition of water-soluble pharmaceutical polymers, the concentration of pregnenolone in HP beta CD was increased more than 60% by the addition of small amounts (0.10%) of (hydroxypropyl)methylcellulose. Mice studies found that while pregnanolone was highly potent in an HP beta CD vehicle, pregnenolone was devoid of activity. Since pregnenolone and pregnanolone differ marginally in structure and physicochemical profile, the data suggest that these derivatives interact via a specific receptor and not via nonspecific membrane perturbations. Sex differences in the action of the pregnanolone complex was observed in that parenteral (i.v. and i.p.) drug administration was more effective in males than females. These data are in contrast to observations made in the case of alfaxalone, a related steroid anesthetic, in which the sex difference favored female animals. On the other hand, females appeared to be more sensitive to the effects of the pregnanolone complex when administered orally. Finally, parenteral pregnanolone was more toxic to males than females with LD50 (i.v.) values of 355 and 548 micromol/kg, respectively.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1995

Expression of vascular cell adhesion molecule-1 by follicular dendritic cells.

Follicular dendritic cells are the major supporting cell of the germinal center microenvironment. The major function of follicular dendritic cells is to present antigen to B cells in secondary lymphoid tissues. Through cell-cell interactions, FDCs are hypothesized to be central to the regulation of normal B cell growth and differentiation. The major receptor-ligand pair which mediates B cell-FDC adhesion is the beta 1 integrin VLA-4, present on B cells and VCAM-1 expressed on FDCs. Follicular non-Hodgkin's lymphomas similarly employ this mechanism to bind to neoplastic germinal centers. The VCAM-1 molecule can exist as a 6 or 7 immunoglobulin domain form. The major form of VCAM-1 on activated endothelium is the 7 domain form. In this report we have determined by polymerase chain reaction of purified FDCs that they express predominantly mRNA for 7 domain VCAM-1. It is likely that the two forms of VCAM-1 are associated with distinct functions, therefore the expression of 7 domain VCAM-1 may be important in normal and neoplastic B cell-FDC interactions.

Base Sequence↗
PubMed1995

Comparison of the outcome between the calculated dosimetry and the estimated dosimetry of 131I in the treatment of hyperthyroidism.

To compare the outcomes of different methods in prescribing the optimal dose of radioactive iodine (131I) for the treatment of hyperthyroidism, we retrospectively analyzed 52 patients with toxic diffuse goiter. They received single dose of 131I for the treatment of hyperthyroidism. In addition, all of them met the following criteria: 1) symptoms and signs of hyperthyroidism; 2) elevated blood triiodothyronine (T3) and thyroxin (T4) by radioimmunoassay (RIA) method; 3) diffuse goiter with increase of uptake proved by thyroid scintiscan; 4) only one dose of 131I was given during the follow-up period; 5) well-documented thyroid function test in the medical chart during the follow-up period (6 months, 1 year, 2 years and 5 years after 131I therapy). The enrolled patients were divided into estimated and calculated group. The dose of 131I in the calculated group was obtained from the measurement of size and 131I uptake of thyroid gland. The dose of 131I in the estimated group was prescribed according to the size of thyroid gland by physical examination, and the association with cardiac arrhythmia, congestive heart failure, or ischemic heart disease. The mean doses of 131I were 4.8 +/- 1.4 mCi and 7.0 +/- 1.1 mCi in the calculated and estimated group respectively. In this study, there were no significant difference in the incidence of euthyroidism, hyperthyroidism, and hypothyroidism between these two groups in thefollow-up period after 131I therapy. In view of simplicity and time-saving, it is a practical choice to prescribe the dose of 131I therapy for toxic diffuse goiter according to the size of thyroid gland and the associated cardiac condition.

Adult↗
PubMed1994

Expression and biochemical characterization of human glucose-6-phosphate dehydrogenase in Escherichia coli: a system to analyze normal and mutant enzymes.

We have developed a system to characterize normal and mutated glucose-6-phosphate dehydrogenase (G6PD) enzymes in vitro. Normal or mutant G6PD cDNA was subcloned into a pGEX-3X vector, which allowed production of a functional fusion protein in Escherichia coli. When we compared the recombinant normal enzyme with authentic human G6PD, indistinguishable Km values for glucose-6-phosphate (G6P) and NADP were obtained, and the utilization rates for two substrate analogues (2-deoxy G6P and deamino NADP) also showed no difference between the enzymes. This system was used to assay a biochemically uncharacterized variant, G6PD Taipei (493 A-->G; 165 Asn-->Asp), plus two other known mutations (487 G-->A; 163 Gly-->Ser and 592 C-->T; 198 Arg-->Cys) that are located close to or within the putative G6P binding domain. Our results show that the G6PD activities of these three mutants were greatly reduced. No significant alteration in G6PD kinetics was observed for both 487 and 493 mutations. However, a drastic reduction in the Km for G6P (4-fold decrease) and tremendous increases in utilization rates of 2-deoxy G6P (32-fold increase) and deamino NADP (6-fold increase) were associated with the 592 mutation. This results suggests that arginine 198 in human G6PD, possibly located within the putative G6P binding domain, may play an important role in binding the substrate G6P. In addition, we and others have recently identified that at least nine different types of mutations are responsible for G6PD deficiency in Chinese. In this report, we also present the occurrence rate of each mutation present in the population of Taiwan.

Base Sequence↗