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Biomedical subjects

H C Chiu

Publications and source records attributed to H C Chiu.

At least 55 records · Page 3Linked to original sources
PubMed1999

A pilot study of topiramate in children with Lennox-Gastaut syndrome.

We conducted an open, add-on study with topiramate (TPM) as adjunctive therapy in Lennox-Gastaut syndrome (LGS), to assess the long-term efficacy and safety and to evaluate quality of life (QL) measurements in the chronic use of TPM. We studied 19 patients (11 male; age ranging from 4 to 14 years) with uncontrolled seizures receiving 2-3 anti-epileptic drugs. Patients were followed up to 36 months of treatment. A questionnaire was used to query parents about QL. Seven patients completed the study at 36 months and seizure frequency was reduced > or = 75% in 4, and < 50% in 3 patients. Two children became seizure free for more than 24 months. Most side effects were CNS related, with the most frequent being somnolence and anorexia. These were generally transient. One patient dropped-out due to powder in the urine. None of the patients required hospitalization. At 36 months, patients' alertness (2/7), interaction with environment (5/7), ability to perform daily activities (5/7), and verbal performance (6/7) improved on TPM. We conclude that TPM may be useful as adjunctive therapy in the treatment of LGS. The efficacy of TPM was maintained in long-term treatment in more than 40% of patients, long term safety was confirmed and QL improved on TPM.

Adolescent↗
PubMed1999

Dominant-inherited hypokalemic periodic paralysis in a large Chinese family.

Familial hypokalemic periodic paralysis (HoPP) is a rare condition among Chinese. We studied a large Chinese family (48 members in six generations) with dominant-inherited HoPP, using incidental tracing of family history of a proband who presented with the typical features of HoPP. Fifteen family members were found to have the disease. We found the familial type of HoPP to differ from the sporadic type in Taiwan, in that the familial type has an equal gender distribution, earlier onset of paralytic attacks, and more severe clinical features in both frequency and extent. When these patients were compared with Caucasian families, the common features were the involvement of the respiratory and the bulbar muscles, and the eye muscles in Chinese patients. Cold-induced attacks and permanent muscle weakness were not common in Chinese subjects. Age and history of paralytic attacks were not the major determinants for the development of permanent muscle weakness. Two family members died during attacks because of severe involvement of the respiratory and bulbar muscles.

Adult↗
PubMed1999

[Immunoadsorption therapy for myasthenia gravis: study on the adsorption capacity of an immunoadsorption column].

Circulating antibodies to the acetylcholine receptor (AchRAb) are detectable in most of the patients with generalized myasthenia gravis (MG). Plasmapheresis has been shown to induce a rapid recovery in company with the decline of the AchRAb titers. Immunoadsorption plasmapheresis (IP) was performed in five patients (three men and two women, mean age 49.6 years) with advanced MG who were refractory to thymectomy and immunosuppressants. Plasmaflo AP 05W was used as a plasma separator and Immusorba TR-350 was used as an immunoadsorption column for plasma perfusion. Each course of treatment consisted of 5 sessions of plasmapheresis on alternate days. Plasma was sampled before and after passage through the adsorption column. We analyzed AchRAb titer in the samples of zero time and sequentially at every 0.5 L of plasma treated. The mean titer of AchRAb in the plasma before passing the adsorption column decreased gradually after every 0.5 L perfused plasma up to 2 L. After perfusion of 2 L plasma, the titer of AchRAb rebounded partly. The mean reduction rate of AchRAb at initial 1 L perfusion of plasma was approximately 100% among sessions of treatment. When the perfusion volume was over 2 L, nearly 50% of AchRAb had not adsorbed through the adsorption column among sessions. The mean titer of AchRAb fell to 74.6%, 52.6%, 43.3%, 35.8%, and 36.5% of the original level after each session of IP. In conclusion, a total of 4 sessions of IP with perfusion of 2 L plasma is an ideal treatment of patients with MG in terms of functional capacity of an immunoadsorption column.

Adult↗
PubMed1998

Allelotype analysis of uterine leiomyoma: localization of a potential tumor suppressor gene to a 4-cM region of chromosome 7q.

Uterine leiomyoma is a benign smooth muscle tumor of the myometrium and is the most commonly encountered neoplasm in women of reproductive age. As for most benign tumors, the pathogenesis of leiomyoma remains obscure, especially at the molecular genetic level. The purpose of this study was to perform a genome-wide allelotype analysis to identify potential sites of tumor suppressor gene inactivation. Fifty-two cases of uterine leiomyoma were subjected to allelotype analysis by using matched pairs of tumor and blood DNA. Loss of heterozygosity (LOH) was assessed at 61 microsatellite markers distributed throughout the genome and representing all 41 chromosome arms. In general, LOH was very rare except on chromosome 7q, where LOH was observed in 34% of all informative tumors. Fine-deletion mapping with 25 microsatellite markers from the 7q22 region revealed a minimal deletion unit of approximately 4 cM, bounded by the markers D7S2453 proximally and D7S496 distally, that probably harbors a novel tumor suppressor gene involved in the etiology of this tumor.

Alleles↗
PubMed1998

Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells.

Curcumin, a potent antioxidant and chemopreventive agent, has recently been found to be capable of inducing apoptosis in human hepatoma and leukemia cells by way of an elusive mechanism. Here, we demonstrate that curcumin also induces apoptosis in human basal cell carcinoma cells in a dose- and time-dependent manner, as evidenced by internucleosomal DNA fragmentation and morphologic change. In our study, consistent with the occurrence of DNA fragmentation, nuclear p53 protein initially increased at 12 h and peaked at 48 h after curcumin treatment. Prior treatment of cells with cycloheximide or actinomycin D abolished the p53 increase and apoptosis induced by curcumin, suggesting that either de novo p53 protein synthesis or some proteins synthesis for stabilization of p53 is required for apoptosis. In electrophoretic mobility gel-shift assays, nuclear extracts of cells treated with curcumin displayed distinct patterns of binding between p53 and its consensus binding site. Supportive of these findings, p53 downstream targets, including p21(CIP1/WAF1) and Gadd45, could be induced to localize on the nucleus by curcumin with similar p53 kinetics. Moreover, we immunoprecipitated extracts from basal cell carcinoma cells with different anti-p53 antibodies, which are known to be specific for wild-type or mutant p53 protein. The results reveal that basal cell carcinoma cells contain exclusively wild-type p53; however, curcumin treatment did not interfere with cell cycling. Similarly, the apoptosis suppressor Bcl-2 and promoter Bax were not changed with the curcumin treatment. Finally, treatment of cells with p53 antisense oligonucleotide could effectively prevent curcumin-induced intracellular p53 protein increase and apoptosis, but sense p53 oligonucleotide could not. Thus, our data suggest that the p53-associated signaling pathway is critically involved in curcumin-mediated apoptotic cell death. This evidence also suggests that curcumin may be a potent agent for skin cancer prevention or therapy.

Apoptosis↗
PubMed1998

Motor end-plate jitter in myasthenia gravis at different firing rates.

Twenty patients with generalized myasthenia gravis (MG) were studied to assess firing rate-dependent changes in end-plate jitter. Stimulated single-fiber electromyography (EMG) was performed in the extensor digitorum communis muscles at stimulation frequencies of 1, 2, 5, and 10 Hz for all the sampled fibers and at 20 Hz for a few ones. In all 137 end-plates were obtained, of which 43 showed blocking. Statistical analysis demonstrated significant increases in jitter and the blocking rate from 1 to 2 and 2 to 5 Hz, whereas there were decreases from 5 to 10 and 10 to 20 Hz. Further analysis showed that the decrement in jitter from 5 to 10 Hz was greater in end-plates with preexisting low safety factors. In contrast, even though the safety factor of long-duration MG end-plates was lower than that of the short-duration group, the decrement in jitter was insignificant in the long-duration MG end-plates. These results suggest that the intratetanic facilitation effect begins at 10 Hz and is more prominent in end-plates with a preexisting low safety factor. Long-lasting MG, however, eliminates this effect.

Adult↗
PubMed1997

Lysosomal degradability of poly(alpha-amino acids).

The lysosomal degradability of poly(alpha-amino acids) based on poly(L-glutamic acid) and its derivatives/copolymers was evaluated to gain insight into the subcellular fate of the macromolecules as water soluble polymeric drug carriers. The results indicate that both the incorporation of hydrophobic comonomers and modification of the carboxylic groups of glutamic acid side chains with hydroxyalkylamine increase the lysosomal degradability of the copolymers. Decreased lysosomal degradability of L-glutamic acid copolymers containing tripeptides terminated in p-nitroanilide (drug model) in the side chains confirmed that drug conjugation alters the degradation pattern of the polymeric carriers. The percentages of the enzymatic release of p-nitroaniline from its polymeric complex with time is relatively independent of the contents of the tripeptidyl p-nitroanilides attached to the polymeric conjugates. Determination of the degradation products by electrospray mass spectroscopy showed that no fragments less than 10(3) D were generated by lysosomal enzymes, whereas the main degradation products by papain and chymotrypsin were tripeptides and tetrapeptides. The conclusions derived from these data strongly suggest that these macromolecules, if used as lysosomotropic drug carriers, may accumulate in the lysosomes and limit their usefulness in some applications.

Animals↗
PubMed1997

Double filtration plasmapheresis in the treatment of inflammatory polyneuropathy.

Twelve cases of recognized inflammatory polyneuropathy were treated by plasmapheresis (PP) at Shin-Kong Wu Ho-Su Memorial Hospital from November 1993 to November 1995. These include 6 cases of acute inflammatory demyelinating polyneuropathy (AIDP), 4 cases of chronic inflammatory demyelinating polyneuropathy (CIDP), one case of Fisher syndrome, and one case of Sjögren's syndrome with polyneuropathy. The patients chosen for PP met the inclusion criteria of severely disabled, i.e., Grade 4 (bed or chair bound) or Grade 5 (required assisted ventilation), or an unremittingly progressive course. Plasmapheresis was carried out by the double filtration method. Each patient received a standard course of at least 4 sessions of pheresis. All the patients receiving PP showed a beneficial response. The treatment for 10 patients was judged to be effective. The other 2 patients (one AIDP and one CIDP), though improved, were unable to reach Grade 2. Among the complications of PP, only 4 episodes of symptomatic hypotension were noted in a total of 73 sessions of PP. In conclusion, PP is safe and effective in treating inflammatory polyneuropathy.

Adult↗
PubMed1997

Low-dose danazol in the treatment of livedoid vasculitis.

BACKGROUND: Livedoid vasculitis is characterized clinically by smooth or depressed ivory-white scars surrounded by hyperpigmentation and telangiectasia with or without preceding purpuric infiltrated papules and plaques and histologically by intravascular deposition of fibrin. Its etiology remains obscure and therapy very difficult. OBJECTIVE: Our purpose was to test the efficacy of low-dose danazol in the treatment of livedoid vasculitis. METHODS: Seven patients with active lesions of livedoid vasculitis were treated with low-dose danazol (200 mg, orally, daily). Laboratory coagulation and fibrinolysis parameters, including antithrombin III, protein C, protein S, tissue plasminogen activator, plasminogen, alpha 2-antiplasmin and fibrinogen, were evaluated before and during the therapy. RESULTS: Six of the 7 patients completed the treatment. After the therapy, all 6 patients had rapid cessation of new lesion formation, prompt reduction in their pain and healing of ulcers. A significant elevation of plasminogen and a decrease in fibrinogen levels were noted 1 month after initiation of the therapy (p = 0.028). The level of fibrinogen seemed to parallel the disease activity in individual patients. In addition, in most of these patients, the levels of antithrombin III, protein C, protein S and alpha 2-antiplasmin tended to increase after the treatment. However, the differences were not statistically significant. Abnormalities of tissue plasminogen activator levels were less consistent. Low-dose danazol was well tolerated without major side effects. CONCLUSION: We concluded that low-dose danazol was effective in the treatment of livedoid vasculitis, without unacceptable side effects.

Administration, Oral↗
PubMed1997

Associations between carotid atherosclerosis and high factor VIII activity, dyslipidemia, and hypertension.

BACKGROUND AND PURPOSE: A subsample of 147 Chinese subjects from a population-based study of cardiovascular diseases (Cardiovascular Disease Risk Factor Two-Township Study) participated in an ancillary study on extracranial carotid color duplex ultrasonography that aimed to assess the relations of coagulation factors to stroke and carotid atherosclerosis. METHODS: Logistic models were used to study the associations between cardiovascular disease risk factors and stroke/carotid atherosclerosis, controlling for the effects of age and sex. RESULTS: Stroke was significantly associated with hypertension and high values of plasma glucose but not with fibrinogen, factor VIIc, or factor VIIIc. Carotid plaques identified in this study were mostly mild and moderate. The presence of these mild and moderate carotid plaques was significantly associated with high values of factor VIII activity, hypercholesterolemia, hypertriglyceridemia, and hypertension. The highest tertile of factor VIIIc (> 1.53) was associated with an odds ratio of 3.35 for carotid atherosclerosis when compared with the lowest tertile (< 1.20). A multiple logistic regression including all significant risk factors showed that the degree of association between factor VIIIc and atherosclerosis was attenuated to an odds ratio of 2.65 (P = .061). CONCLUSIONS: In the present study, the roles of hypertension, hypercholesterolemia, and hypertriglyceridemia have been implicated in the pathogenesis of carotid atherosclerosis, and roles for hypertension and hyperglycemia in stroke were indicated. A positive association between factor VIIIc and carotid atherosclerosis in this Chinese population was found. Whether this association is independent of the effect of other cardiovascular risk factors awaits further study.

Adult↗
PubMed1997

Overview of the hospital formulary systems in Hong Kong. Princess Margaret Hospital as a baseline.

OBJECTIVE: To investigate the popularity of formulary systems in all Hong Kong hospitals and to compare these with the newly introduced formulary system in a major government hospital, the Princess Margaret Hospital (PMH), as the baseline. DESIGN: Questionnaire and selected interviews by pharmacy students. SETTING: All hospital pharmacies in Hong Kong. PARTICIPANTS: Department managers (directors of pharmacy services) of hospital pharmacies. MAIN OUTCOME MEASURE: The popularity of the hospitals' formulary systems and their formulary decision-making strategies. Calculations of cost savings of the new formulary system in PMH and a comparison of the PMH system with the US standards were also made. RESULTS: Among 38 responding hospitals, 35 (92%) had a formulary handbook and 21 (55.3%) claimed to have a formulary system. The evaluation processes and formulary decision-making procedures were found to be inadequate because basic components in drug evaluation (e.g., standardized criteria for drug evaluation) were not used regularly. However, the formulary system in PMH was found to be comparable with the US standards. Substantial cost savings were made through rejection of less cost-effective drugs by the Formulary Subcommittee in PMH. CONCLUSIONS: In general, comprehensive formulary systems are still not popular in Hong Kong. This may be due to insufficient staffing and lack of administrative and physicians' support. The new formulary system in PMH can be used as a model to develop a successful formulary system in which hospital pharmacists can prove their expertise for the benefit of both hospitals and patients in Hong Kong.

Attitude of Health Personnel↗
PubMed1996

Mutations of the BRCA2 gene in ovarian carcinomas.

Inherited mutations in the recently discovered BRCA2 gene are believed to be responsible for a significant fraction of early-onset hereditary breast cancers. Unlike BRCA1, however, which confers a high risk to both breast and ovarian cancer, the incidence of ovarian cancer appears to be much lower In BRCA2-linked families, causing uncertainty as to the relevance of BRCA2 to hereditary ovarian cancer. Numerous allelotype studies indicate that allelic deletions Including the BRCA2 locus on chromosome 13q are common in ovarian cancers in general, suggesting that somatic mutations of this gene may be involved in sporadic ovarian tumorigenesis. The purpose of this study was to test the hypothesis that germline or somatic mutations of BRCA2 are associated with hereditary and/or sporadic ovarian cancers, respectively. The entire 10.2-kb coding region of BRCA2 was screened for mutations in 130 consecutive ovarian tumors, the only selection criterion being a pathological diagnosis of epithelial ovarian carcinoma. Loss of heterozygosity at markers flanking BRCA2 was observed in 56% of the tumors. Four germline mutations and two somatic mutations were identified; two of the germline mutations are recurrent, having been previously described. Remarkably, the patients with germline mutations were late-onset cases with no medical or family histories suggestive of hereditary cancer. These data suggest that mutations of BRCA2 are rare in sporadic ovarian cancers, and that the proportion of ovarian cancers resulting from hereditary predisposition may be higher than previously suspected based on estimates derived from studies of highly penetrant genetic loci.

Aged↗
PubMed1996

Effects of humic acid on the viability and coagulant properties of human umbilical vein endothelial cells.

We have previously shown that humic acid (well-water humic acid, HA, and synthetic humic acid, SHA) enhances cell surface expression of tissue factor (TF). Here we report that incubation of human umbilical vein endothelial cells (HUVEC) for 2 hr with HA or SHA cause a rapid rise in TF mRNA levels, as shown by Northern blot analysis. To understand the cytotoxic and fibrinolytic effects of HA and SHA on cultured HUVEC, the cells treated with varying concentrations of HA and SHA for various periods of time. Both HA and SHA (10-200 micrograms/ml) inhibited the viability of subconfluent HUVEC, cultured in the presence or absence of 20% FBS (Fetal Bovine serum) in the culture medium, in a dose-dependent manner. Both HA and SHA induced surface changes in the HUVEC as revealed by scanning electron micrography (SEM). However, protocatechuic acid, the monomer of SHA, did not significantly inhibit cell growth, and showed a cytotoxic effect only at 200 micrograms/ml. Furthermore both HA and SHA stimulated HUVEC to produce plasminogen activator inhibitor (PAI-1) and tissue plasminogen activator (t-PA) in a dose and time dependent fashion; the amount of PAI-1 produced was found to exceed that of t-PA. The monomer of SHA did not have this stimulatory effect. These results distinctly suggest that in addition to the inhibition of viability HA is involved in TF induction and PAI-1 synthesis in HUVEC and these may be some of the plausible mechanisms underlying the thrombotic disorders in Blackfoot disease.

Arterial Occlusive Diseases↗