PubMed Health⌕ Search

Biomedical subjects

P Choi

Publications and source records attributed to P Choi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Strong association between hyperferritinaemia and metastatic disease in nasopharyngeal carcinoma.

We have investigated the role of serum ferritin, in relation to disease stages, in patients with nasopharyngeal carcinoma. Patients with localised disease (Ho's stage I-IV) had levels which were not significantly different from age, sex matched normal subjects and there was no relationship between mean serum ferritin levels and stage. However, in patients with metastatic disease levels were grossly elevated with mean levels increased more than 6-fold compared to normal subjects and patients with localised disease. Furthermore, among the small group of patients with localised disease but hyperferritinaemia, the subsequent development of metastatic disease within 1 year was significantly much higher (32.4%) than in those with levels falling within the reference range (10.3%). Hyperferritinaemia is strongly associated with, and may predict, metastatic disease in patients with nasopharyngeal carcinoma.

Adult↗
PubMed1996

A retrospective study of the role of intracavitary brachytherapy and prognostic factors determining local tumour control after primary radical radiotherapy in 903 non-disseminated nasopharyngeal carcinoma patients.

The aims of this retrospective study were to determine the role of intracavitary brachytherapy given shortly after external beam radiotherapy in the primary radical treatment of non-metastatic nasopharyngeal (NPC) cancer patients, and the prognostic factors governing local tumour control. From 1984 to 1989, 903 patients with non-disseminated NPC who had had no previous treatment were managed at the Prince of Wales Hospital, where investigation and treatment methods had been standardized according to a departmental protocol. The external radiotherapy dose of 60.0-62.5 Gy in 6 weeks was given to all patients. Parapharyngeal booster radiotherapy with a single photon beam to 20 Gy in 2 weeks was given to those with parapharyngeal tumour extension. Computed tomography of the nasopharynx and skull base, and pretreatment nasopharyngoscopy and biopsy were performed in all patients. Nasopharyngoscopy was repeated at 4 weeks after the last day of external irradiation. Local persistence in 99 patients was treated additionally by intracavitary brachytherapy to 24 Gy in three fractions over 15 days. Fifty-one patients with early stage primary disease (Ho Stage T1 and T2n (nasal)) who responded completely to external radiotherapy were given adjuvant intracavitary brachytherapy to 18 Gy in three fractions over 15 days. Intracavitary therapy was an inadequate salvage treatment for the locally persisting T3, T20 (oropharyngeal) and T2p (parapharyngeal) disease, but there was a trend towards improved local control after intracavitary brachytherapy for the locally persisting T1 tumours. Adjuvant brachytherapy did not enhance local tumour control for the early T-stage tumours that completely responded to external radiotherapy. Both forms of intracavitary brachytherapy were safe with few and acceptable complications. In the 903 non-disseminated NPCs, the patient's age and tumour involvement of the skull base and cranial nerves were significant independent prognostic factors governing local tumour control. In the 358 patients with Ho T3 disease, tumour involvement of the orbits and the laryngopharynx significantly worsened local tumour control. The presence of local persistence at 4 weeks after external radiotherapy, for which therapeutic brachytherapy was given, was marginally significant as a prognostic factor in addition to the presence of cranial nerve palsy.

Actuarial Analysis↗
PubMed1996

Transcription of the glutamyl-tRNA reductase (hemA) gene in Salmonella typhimurium and Escherichia coli: role of the hemA P1 promoter and the arcA gene product.

In Salmonella typhimurium and Escherichia coli, the hemA gene encodes the enzyme glutamyl-tRNA reductase, which catalyzes the first committed step in the heme biosynthetic pathway. It has recently been reported that a lac operon fusion to the hemA promoter of E. coli is induced 20-fold after starvation for heme. Induction was dependent on the transcriptional regulator ArcA, with a second transcriptional regulator, FNR, playing a negative role specifically under anaerobic conditions (S. Darie and R. P. Gunsalus, J. Bacteriol. 176:5270-5276, 1994). We have investigated the generality of this effect by examining the response to heme starvation of a number of lac operon fusions to the hemA promoters of both E. coli and S. typhimurium. We confirmed that such fusions are induced during starvation of a hemA auxotroph, but the level of induction observed was maximally sixfold and for S. typhimurium fusions it was only two- to fourfold. Sequences required for high-level expression of hemA lie within 129 bp upstream of the major (P1) promoter transcriptional start site. Mutants defective in the P1 promoter had greatly reduced hemA-lac expression both in the presence and in the absence of ALA. Mutations in arcA had no effect on hemA-lac expression in E. coli during normal growth, although the increase in expression during starvation for ALA was half that seen in an arcA+ strain. Overexpression of the arcA gene had no effect on hemA-lac expression. Primer extension analysis showed that RNA 5' ends mapping to the hemA P1 and P2 promoters were not expressed at significantly higher levels in induced cultures. These results differ from those previously reported.

Aldehyde Oxidoreductases↗
PubMed1996

Early tumour response and treatment toxicity after hyperfractionated radiotherapy in nasopharyngeal carcinoma.

The aim of the present study was to undertake a planned interim analysis of a prospective randomized trial comparing the tumour response and the acute and subacute complications of hyperfractionated radiotherapy and conventional radiotherapy in non-metastatic nasopharyngeal carcinoma (NPC). 100 patients with newly diagnosed non-metastatic NPC were randomized to receive either conventional radiotherapy (Arm I) or hyperfractionated radiotherapy (Arm II). Stratification was done according to the T-Stage (modified Ho's T-Stage classification). The biological effective dose (10 Gy) to the primary and the upper cervical lymphatics were 75.0 and 73.1 for Arm I and 84.4 and 77.2 for Arm II, respectively. Hyperfractionated radiotherapy was associated with significant mucositis which is of higher grade than conventional radiotherapy (p = 0.0001), but the duration of mucositis was similar between the two Arms and all study patients completed radiotherapy on schedule without interruption of radiotherapy. Early survival and tumour recurrence rates were comparable between the Arms. The preliminary results indicate that the hyperfractionated radiotherapy has excellent patient compliance in Chinese patients, with acceptable acute and subacute toxicities and the local and regional complete tumour response rates being comparable with conventional radiotherapy. The significance of the time required after start of radiotherapy to achieve a complete tumour response is discussed.

Carcinoma↗
PubMed1995

Interaction of manganese-mesoporphyrin with oleic acid vesicles.

We investigated the interaction between manganese(III)mesoporphyrin (MnMeso), a metalloporphyrin, and liposome membranes containing oleic acid (OA; cis-9-octadecenoic acid). MnMeso associates preferentially with OA but minimally with egg phosphatidylcholine (EPC). Using small unilamellar vesicles, we characterized the MnMeso-OA binding at neutral pH. Our data suggest that MnMeso binds to the OA bilayer with Kd = 6.8 x 10(-4) M; the binding stoichiometry of MnMeso-OA was 1:3.4. This OA-MnMeso interaction was analyzed further for changes in the T1 relaxation property of MnMeso. OA increased the T1 of MnMeso significantly more than did EPC, suggesting that the OA-MnMeso interaction was stronger than that of PC-MnMeso. The side-chain specificity of the OA interaction with this porphyrin derivative was further supported in an experiment with manganese mesotetra(4-sulfonatophenyl)porphine, which lacks hydrophobic side chains for OA interaction. The association of MnMeso with the OA membrane was proposed according to the structure of MnMeso and OA and further verified using electron microscopy. A strong association of MnMeso with OA, an absorption enhancer of the gastrointestinal tract, may be useful for delivery of MnMeso as an oral contrast agent for magnetic resonance imaging.

Animals↗
PubMed1994

Afterloading radiotherapy for local persistence of nasopharyngeal carcinoma.

71 patients suffering from local persistence of nasopharyngeal carcinoma after primary external radiotherapy were treated by afterloading intracavitary 192Ir. 66 (93.0%) had a complete response as evidenced by fibreoptic nasopharyngoscope examination and biopsy 4 weeks after the treatment. Significant prognosticators were studied by both monovariate and multivariate analysis. The early overall clinical stage at first presentation predicted a favourable survival. Local tumour control was adversely affected by advanced T-stage at first presentation, and by using a single 192Ir source, unilaterally applied to treat only one side of the nasopharynx. The intracavitary treatment was tolerated well and treatment complications were confined to the nasopharynx: chronic radiation ulceration (five patients) and diffuse telangiectasia (three patients).

Brachytherapy↗
PubMed1993

Multicenter phase II trial of mitoxantrone in patients with advanced nasopharyngeal carcinoma in Southeast Asia: an Asian-Oceanian Clinical Oncology Association Group study.

PURPOSE: Patients with advanced nasopharyngeal carcinoma (NPC) have a high incidence of recurrence and often develop distant metastases despite local control. This prospective multicenter phase II trial was conducted to evaluate the safety and efficacy of Novantrone (mitoxantrone; Lederle Laboratories, Wayne, NJ) in the therapy of patients with advanced NPC. PATIENTS AND METHODS: One hundred eight patients with advanced NPC, namely, those with recurrent or persistent disease following primary radiotherapy, or newly diagnosed metastatic disease, were treated with mitoxantrone. Mitoxantrone was administered intravenously at an initial dose of 12 mg/m2 and repeated every 3 weeks, with dose escalation to a maximum of 14 mg/m2. The distribution of histologic subtypes was representative of NPC, with the majority being (61%) undifferentiated (or anaplastic) carcinoma. RESULTS: The overall response rate (complete response [CR] and partial response [PR]) was 25% (95% confidence interval, 17% to 33%). The median response duration, time to treatment failure, and survival duration were 140, 82, and 394 days, respectively. Histology (poorly differentiated squamous cell) was found to be the only important factor in predicting response (P = .04) based on a multivariate analysis of nine pretreatment characteristics. The major dose-limiting toxicity was leukopenia. The incidences of nausea/vomiting, alopecia, and stomatitis/mucositis were 34%, 6%, and 3%, respectively. None were severe. Two patients had asymptomatic, moderate Alexander-grade cardiotoxicity. CONCLUSION: This study represents a large, controlled multicenter trial of single-agent mitoxantrone in the treatment of advanced NPC. Mitoxantrone was well tolerated and produced an overall response rate comparable to that of other single-agent therapies used in the treatment of advanced head and neck cancer. Combination trials with mitoxantrone for advanced disease should be considered.

Adult↗
PubMed1992

Absence of p53 gene mutations in primary nasopharyngeal carcinomas.

Alterations in the p53 tumor suppressor gene and Epstein-Barr virus status were investigated in 15 nasopharyngeal carcinoma (NPC) biopsies, 4 xenografts, and 2 cell lines from the Cantonese region of southern China. One other established NPC cell line obtained from a northern Chinese patient was also studied. Restriction fragment length polymorphism analysis revealed a loss of heterozygosity for chromosome 17p, where the p53 gene resides, in only one of 15 NPC biopsies. Polymerase chain reaction-single-stranded conformational polymorphism analysis and direct sequencing failed to detect sequence alterations in exons 5 through 8 of the p53 gene in the 15 tumors and in the 4 NPC xenografts, all of which tested positive for Epstein-Barr virus. In contrast, the 3 NPC cell lines were all negative for Epstein-Barr virus and contained G----C transversions in the p53 gene, with cell lines CNE-1 and CNE-2 harboring identical AGA (arginine) to ACA (threonine) changes at codon 280. These results suggest that p53 inactivation is not a necessary component of nasopharyngeal carcinogenesis in Cantonese but may be important in the establishment of cell lines derived from these tumors.

Base Sequence↗
PubMed1992

Soft tissue sarcoma: the experience of a regional hospital in Hong Kong.

The clinical features and treatment results of 66 soft tissue sarcomas (STS) were reported from a regional hospital in Hong Kong. The nature of the locoregional treatment and the grade were the chief prognostic factors governing survival and local control. Radical surgery (amputation/radical local resection) was determined by the site, the extent of the STS and potential functional loss. Complete resection with a variable margin followed by post-operative radiotherapy (60-70 Gy) produced survival and local tumour control similar to that of radical surgery. Incomplete surgery (partial excision/biopsy only) was associated with significantly poorer, survival and local tumour control, despite the administration of radiotherapy. Palliative chemotherapy for metastatic or recurrent STS has been disappointing, with low tumour response rates, while first line and adjuvant chemotherapy was difficult to assess for its efficacy in the present study. The overall survival of non-metastatic STS was comparable to that reported from developed countries. Suggestions are made to improve treatment results of STS in Hong Kong.

Actuarial Analysis↗
PubMed1992

High-dose-rate remote afterloading irradiation of carcinoma of the cervix in Hong Kong: unexpectedly high complication rate.

One hundred and thirty-six patients with biopsy-proven carcinoma of cervix were treated with external beam irradiation to the whole pelvis (46 Gy in 23 fractions) and three weekly applications of high-dose-rate (HDR) intracavitary brachytherapy of 7 or 8 Gy per fraction to point A (2 cm above and 2 cm lateral to the cervical os). The actuarial 5-year survival rate was 72% (Stage IB 85%; IIA 64%; IIB 70%; IIIA 25%; IIIB 53%). Patient age above 61 years and Stage III disease were adverse determinants for survival as shown by multivariate analysis. Late complications developed in 47% (65/137) of patients. Grade 3 or above complications occurred in the bladder, small bowel and sigmoid colon/rectum in 5%, 3% and 7% of patients, respectively. The most significant determinant of severe rectal complications was the addition of a lower vaginal tandem (P less than 0.01); the other determinants of rectal complications included a uterine length greater than 5 cm, a total biologically effective dose to the rectum of more than 120 Gy3 and Stage III disease.

Adult↗
PubMed1990

Possible role of H1 histone in the differentiation of mouse erythroleukemia cells.

Serum-starved mouse erythroleukemia cells, stationary phase cells or cells cultured in dibutyryl cAMP (1 mM) can be induced to differentiate by addition of 20% fetal calf serum plus cycloheximide. Culturing unstarved log phase cells in 20% fetal calf serum plus low levels of cycloheximide and histone H1 also causes a significant level of differentiation. These same concentrations of cycloheximide and H1 histone employed separately with 20% fetal calf serum do not induce differentiation. The role these procedures may have in causing an accumulation of histone H1 and cell differentiation is discussed.

Animals↗
PubMed1990

Discriminant factors affecting early outcome of radioiodine treatment for Graves' disease.

Pretreatment clinical, biochemical, iodine-131 (131I) scan and tracer-kinetic parameters were studied in 827 Chinese patients with Graves' disease treated with radioactive iodine. One year after 131I therapy, 56.7% were euthyroid, 33.9% were still thyrotoxic and 9.4% were hypothyroid. Discriminant analysis of all pretreatment variables identified thyroid mass, presenting free thyroxine index and 4 h 131I uptake as the three variables most helpful in discriminating the early outcome group of 131I therapy. The findings suggest that patients with large goitres and severe disease may require higher doses of 131I for treatment of Graves' disease.

Adult↗
PubMed1990

A patient education program to improve adherence rates with antituberculosis drug regimens.

The design, logic, and results of a two-year health education study directed at improving rates of patient adherence to antituberculosis medical regimens are presented. An incentive scheme to reward positive health behaviors plus targeted educational counseling sessions was implemented in a randomized clinical controlled trial. The 205 subjects who participated in the study are categorized according to patients with active tuberculosis (n = 88) or preventive patients with no evidence of active disease (n = 117). Patients in each of these groups were randomly assigned to a special intervention (SI) group or a usual care (UC) control group and were followed monthly throughout their treatment program. While SI patients with active tuberculosis demonstrated higher levels of appointment-keeping behavior and mean percent of medication taken compared to UC patients, no statistically significant differences between the two groups were found. Preventive therapy patients assigned to the SI group, however, were significantly more likely than UC patients to remain in care during their 12-month regimen (64% vs 47%; p = .003). Furthermore, SI patients had significantly higher levels of adherence to their medical regimen compared to UC patients (68% vs 38%; p less than .001). These results demonstrate the positive effects of a structured health education program on the improvement of continuity of care and adherence behavior among patients with tuberculosis.

Adolescent↗
PubMed1990

Long-term results following 131I treatment for Graves' disease in Hong Kong Chinese--discriminant factors predicting hypothyroidism.

The clinical outcome of 1028 Hong Kong Chinese patients with Graves' disease treated with radioiodine therapy and followed for a mean of 9.85 +/- 4.84 years (range 2-20) was analysed. Retreatment was required by 413 patients (40.2 per cent), with 134 patients (13.0 per cent) requiring more than two 131I doses. One hundred and eighty-nine patients received carbimazole after 131I until euthyroidism was achieved. The cumulative incidence of hypothyroidism at one, five, 10 and 15 years was 9.6 per cent, 31.4 per cent, 53.8 per cent and 65.8 per cent, respectively. The average incidence of hypothyroidism after the first two years was 3.3 per cent per annum. Stepwise logistic regression analysis of pretreatment variables suggested that a combination of adjunctive carbimazole therapy, absence of ophthalmopathy and longer effective half-lives of 131I were of value in predicting which patients were less likely to develop permanent hypothyroidism. However, the probability of accurately predicting permanent hypothyroidism based on the present model was only 60 per cent. We believe that no single pretreatment variable, or combination of variables, predicts long-term hypothyroidism with sufficient confidence to justify the use of a 'formula' approach for prescribing 131I therapy for Graves' disease.

Adolescent↗
PubMed1989

Long-term effects of megavoltage radiotherapy in acromegaly.

The progress of 41 Chinese patients with acromegaly treated with megavoltage radiotherapy was reviewed after a mean follow-up of 4.5 (one-ten) years. Nine received prior surgery. Radiotherapy was delivered by a 3-field technique to a total of 4000-5000 cGy in 25 fractions. By life table analysis successful treatment of growth hormone (GH) hypersecretion, as defined by a mean GH concentration of less than or equal to 10 mu/L, could be expected in 6, 11, 26, 64 and 67% of the patients after one, two, five, eight and ten years respectively. Median intervals before achieving a mean GH level of less than or equal to 10 mu/L were 6.6 and 8.6 years following radiotherapy with the higher (4500-5000 cGy) and lower (4000 cGy) doses respectively, suggesting a tendency towards earlier response following radiotherapy with the higher dose. The prevalence of acquired hypopituitarism in patients followed up for over five years was 40% for gonadotrophins, 30% for TSH and 20% for ACTH deficiency respectively. In the majority of patients, acquired hypopituitarism was not apparent within five years after radiotherapy. No mortality or major side effects were noted following radiotherapy. In 34 patients on long-term bromocriptine treatment, mean GH concentrations were normalised in 26.5% of patients. We conclude that with judicious selection of patients and use of adjunctive medical therapy, megavoltage radiotherapy remains a safe and satisfactory form of treatment for acromegaly especially if expert transphenoidal surgery is not readily available.

Acromegaly↗