Biomedical subjects

H M Chang

Publications and source records attributed to H M Chang.

At least 19 recordsLinked to original sources

PubMed2007

Adjuvant chemotherapy with 5-fluorouracil, doxorubicin and mitomycin-C (FAM) for 6 months after curative resection of gastric carcinoma.

AIM: This study aimed to evaluate the efficacy and safety of 5-fluorouracil (5-FU), doxorubicin and mitomycin-C (FAM) adjuvant chemotherapy in patients who had undergone curative resection of gastric carcinoma. METHODS: From Nov 1999 to Jan 2002, 291 consecutive patients with stage IB-IIIB gastric adenocarcinoma were given FAM adjuvant chemotherapy. Chemotherapy comprised intravenous 5-FU 600 mg/m(2) (days 1, 8, 29 and 36), doxorubicin 30 mg/m(2) (days 1 and 29) and mitomycin-C 10 mg/m(2) (day 1), every 8 weeks for 6 months. RESULTS: The median follow-up time was 60.6 months, 92 patients died, and 93 patients had recurrent disease. The 5-year overall survival (OS) rates were 85.9% for stage IB, 72.1% for stage II, 58.0% for stage IIIA, and 48.2% for stage IIIB (p=0.002). The 5-year relapse-free survival (RFS) rates were 85.2% for stage IB, 71.2% for stage II, 53.3% for stage IIIA, and 39.2% for stage IIIB (p<0.001). A total of 769 cycles of chemotherapy were delivered, and 15 patients experienced grade 3 or higher leukopenia. The most common grade 3 or higher non-hematologic toxicity was nausea/vomiting (11 patients), followed by stomatitis (3 patients). CONCLUSIONS: Adjuvant chemotherapy with FAM for 6 months for gastric carcinoma indicated comparable RFS and OS with an acceptable toxicity profile.

Adenocarcinoma↗

PubMed2006

Efficacy of PET/CT in the accurate evaluation of primary colorectal carcinoma.

AIM: This study was performed to assess in the accurate evaluation of primary colorectal carcinoma using PET/CT. METHODS: One hundred patients with primary colorectal carcinoma were evaluated during 2004. All patients underwent PET/CT when their preoperative serum carcinoembryonic antigen was >or=10 ng/mL or when CT showed equivocal findings. The appropriateness of PET/CT-induced changes was noted by subsequent operative findings and follow-up. RESULTS: PET/CT more detected 15 intra-abdominal metastatic lesions than abdomino-pelvic CT scan. PET/CT showed true negative findings in 13 patients and false positive or negative findings in 10. Due to PET/CT results, management plans were altered in 27 patients; 9 had inter-modality changes, 10 received more extensive surgery, and 8 avoided unnecessary procedures. CONCLUSIONS: PET/CT altered management plan in 24% of patients with primary colorectal carcinoma in correct direction. These findings suggest that PET/CT should be considered a part of standard work up for preoperative evaluation in a subset of patients with colorectal carcinoma.

Adult↗

PubMed2006

Identification and characterization of novel low-density lipoprotein receptor mutations of familial hypercholesterolaemia patients in Taiwan.

BACKGROUND: Familial hypercholesterolaemia (FH) is an autosomal dominant disease associated with a very high risk of coronary vascular disease. The study objective was to identify patients with FH in Taiwan and characterize novel mutations. MATERIALS AND METHODS: Fifty-one patients with suspected FH living in Taiwan were screened for mutations in both the low-density lipoprotein (LDL) receptor and the apolipoprotein (apoB) genes using the multiplex polymerase chain reaction and exon-by-exon DNA sequencing technique. Functional consequences on LDL receptor activity were characterized in vitro for novel mutations and family pedigree was also analyzed. RESULTS: Thirteen different functional mutations in the LDL receptor gene and one mutation in the apoB gene were found in 21 patients. Among the 13 mutations in the LDL receptor gene, 10 were single-point missense mutations, one was a two-point mutation in the same allele, one was a non-sense mutation and one was a frame-shift mutation. There were three novel mutations, including two missense mutations (M510K and W512R) and one frame-shift mutation (1953 delTA mutation). The characterization of missense M510K retained 36.2% of the activity of the normal receptor. Conversely, frame-shift 1953 delTA and missense W512R led to defective proteins, with only 0-6% of normal receptor activity. CONCLUSIONS: The study identified 13 LDL receptor gene mutations and characterized three novel mutations causing FH in Taiwan. This facilitated a better understanding of FH among the Chinese population and may enable diagnosis of FH at the molecular level at a presymptomatic, early age.

Aged↗

PubMed2005

An alternative technique for totally implantable central venous access devices. A retrospective study of 1311 cases.

AIM: The aim of the present study was to report our experience of totally implantable central venous access devices (TICVAD) implantation using two techniques and attempt to define the better technique. MATERIALS AND METHODS: From January 1998 to September 2003, 1131 patients were reviewed and divided into two groups with implantation by cephalic vein cut-down (group A) done by general surgeons and subclavian vein puncture with the Seldinger technique (group B) done by vascular surgeons. The operative time, early and late complications of these two groups were compared. Data were analysed by Student's t-test. RESULTS: The average of operative time was 43 min in group A (35-70 min) and 40 min in group B (35-60 min) (P>0.05). No post-operative pneumothorax, hemothorax and fragmentation occurred in group A; the incidence of peri-operative complication was higher in group B. The overall and early complications of group A were significantly lower than that of group B (P<0.0001). CONCLUSION: This retrospective study showed that the cephalic vein cut-down approach for TICVAD placement avoided the risks of pneumothorax, hemothorax and catheter fragmentation.

Blood Vessel Prosthesis Implantation↗

PubMed2005

Phase II study of capecitabine and cisplatin as first-line combination therapy in patients with gastric cancer recurrent after fluoropyrimidine-based adjuvant chemotherapy.

To evaluate the efficacy and safety of capecitabine and cisplatin in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant therapy. Patients with histologically confirmed and measurable advanced gastric cancer that had relapsed after fluoropyrimidine-based adjuvant chemotherapy received oral capecitabine (1250 mg m(-2) twice daily, days 1-14) and intravenous cisplatin (60 mg m(-2) over 1 h, day 1) every 3 weeks. In total, 32 patients were enrolled, of whom 30 were evaluable for efficacy and 32 for safety. A median of 5 cycles (range 1-10) was administered. One patient achieved a complete response and eight had partial responses, giving an overall response rate of 28% (95% CI, 13-44%). The median time to progression and median overall survival were 5.8 months (95% CI, 4.1-7.5 months) and 11.2 months (95% CI, 5.5-16.9 months), respectively. Grade 3 neutropenia and thrombocytopenia were observed in 38 and 6% of patients, respectively. Grade 2/3 nonhaematological toxicities included diarrhoea (19%), stomatitis (19%) and hand-foot syndrome (31%). No grade 4 toxicity, neutropenic fever or treatment-related deaths occurred. Capecitabine in combination with cisplatin was effective and well tolerated as first-line treatment in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant chemotherapy.

Administration, Oral↗

PubMed2004

Imaging cells and tissues with refractive index radiology.

Can individual cells, including live cells, be imaged using hard x rays? Common wisdom until now required sophisticated staining techniques for this task. We show instead that individual cells and cell details can be detected in culture solution and tissues with no staining and no other contrast-enhancing preparation. The sample examined can be much thicker than for many other microscopy techniques without sacrificing the capability to resolve cells. The key factor in our approach is the use of a coherent synchrotron source and of contrast mechanisms based on the refractive index. The first successful tests were conducted on a variety of cell systems including skin and internal leaf cells, mouse neurons, rabbit fibroblast cells, and human tumor cells.

Animals↗

PubMed2004

The clinicopathological significance of inferior mesenteric lymph node metastasis in colorectal cancer.

AIMS: There are few studies reporting survival or recurrence patterns in colorectal cancer patients with inferior mesenteric lymph node metastasis (IMLN+). The present study evaluated the prognostic significance of patients being IMLN+ or IMLN- in colorectal cancer. METHODS: Survival, recurrence pattern and treatment protocols were compared between 63 IMLN+ patients and 108 IMLN- patients with stage III and IV rectal and sigmoid cancer undergoing curative surgery. Lymph node sampling was routinely performed prior to inferior mesenteric artery ligation and excision flush with aorta. Limited principal node dissection including IMLN was performed in cases of identified node metastasis. RESULTS: The 5-year disease-free survival rates were 50% in IMLN- and 31% in IMLN+ patients (P=0.004). The 5-year disease-free survival rate was greater in the N1 group than the N2 group (P=0.038). Cox regression analysis showed IMLN+, lymphovascular tumour invasion, T4, M1, and pre-operative serum CEA level over 6 ng/ml were independently associated with unfavorable disease-free survival. The prognostic significance of M category was greater when the IMLN+ was included in the M1 as opposed to the N category. In patients undergoing absolute curative surgery, post-operative recurrence rates were 34% for IMLN- and 57% for IMLN+ patients (P=0.009; OR, 2.611; 95% CI, 1.313-5.194). For IMLN+ patients, post-operative adjuvant treatment independently correlated with disease-free survival (P=0.029). CONCLUSIONS: IMLN+ is an independent survival factor enhancing the prognostic significance of the M category in the AJCC staging. Curative radical surgery and post-operative chemoradiotherapy appears to be warranted for IMLN+ colorectal cancer patients as it resulted in 5-year disease-free survival rates of up to 31% compared to 50% in IMLN- patients.

Adult↗

PubMed2003

Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced biliary cancer.

BACKGROUND: A phase II study was conducted to assess the efficacy and tolerability of substituting capecitabine for 5-fluorouracil in combination with cisplatin in patients with advanced biliary cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic or unresectable measurable biliary adenocarcinoma received oral capecitabine 1250 mg/m(2) twice daily on days 1-14, and intravenous cisplatin 60 mg/m(2) on day 1. This cycle was repeated every 21 days. RESULTS: Forty-two patients were enrolled in this study. Of these, 38 were assessable for efficacy and 41 were assessable for safety. A median of three cycles of treatment (range one to eight) were administered. One patient achieved a complete response, and eight had partial responses, giving an overall response rate of 21.4% in the intention-to-treat population (95% confidence interval 9.1% to 33.9%). The median response duration was 5.1 months. The median time to progression and median overall survival were 3.7 and 9.1 months, respectively. The most common grade 3/4 adverse events were neutropenia (20% of patients), vomiting (12%), diarrhea (7%) and stomatitis (5%). There were no treatment-related deaths. CONCLUSIONS: The combination of capecitabine and cisplatin has promising antitumor activity and is well tolerated in patients with advanced biliary cancer.

Administration, Oral↗

PubMed2002

A phase III randomized trial of 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil and mitomycin C versus 5-fluorouracil alone in curatively resected gastric cancer.

BACKGROUND: A phase III single-center randomized trial was performed in order to determine whether the addition of mitomycin C (MMC) and/or doxorubicin to 5-fluorouracil (5-FU) as adjuvant chemotherapy could influence survival in patients with curatively resected gastric cancer. PATIENTS AND METHODS: A total of 416 patients who had undergone curative resection for stage IB-IIIB gastric adenocarcinoma were stratified according to the stage and type of surgery, and then randomized to receive one of the three chemotherapy regimens, 5-FU alone (F) or 5-FU and MMC (FM) or 5-FU, doxorubicin and MMC (FAM) within 5 weeks after surgery. RESULTS: Of 416 patients registered, 395 (133 in F, 131 in FM and 131 in FAM) were assessable. Median follow-up duration was 91 months. Five-year overall survival rates were 67.2% for F, 67.0% for FM and 66.7% for FAM (P = 0.97). Five-year disease-free survival rates were 62.1% for F, 63.3% for FM and 62.5% for FAM (P = 0.83). Hematological toxicities were more frequent in the FM and FAM groups, whereas stomatitis was more common in the F group. CONCLUSIONS: Compared with adjuvant 5-FU alone, the addition of MMC and/or doxorubicin to 5-FU did not influence survival in patients with resected gastric cancer.

Adenocarcinoma↗

PubMed2002

Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced gastric cancer.

BACKGROUND: A phase II study was conducted to assess the efficacy and tolerability of combination therapy with capecitabine and cisplatin in patients with advanced gastric cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic or unresectable measurable gastric adenocarcinoma received oral capecitabine 1250 mg/m(2) twice daily, days 1-14, and i.v. cisplatin 60 mg/m(2) on day 1. This cycle was repeated every 3 weeks. RESULTS: Forty-two patients were enrolled in this study. Of these, 38 patients were assessable for efficacy and 40 were assessable for toxicity. One patient achieved a complete response and 22 patients had partial responses, giving an overall response rate of 54.8% in the intention-to-treat population (95% confidence interval 39.8% to 69.8%). The median time to progression was 6.3 months and the median overall survival was 10.1 months. The principal adverse events were neutropenia and hand-foot syndrome. Grade 3/4 adverse events were neutropenia (32.5% of patients), thrombocytopenia (10%), stomatitis (2.5%) and diarrhea (5%). Grade 2 and 3 hand-foot syndrome occurred in 20% and 7.5% of patients, respectively. There were no treatment-related deaths. CONCLUSIONS: The combination of capecitabine and cisplatin is active and well tolerated in patients with advanced gastric cancer.

Adenocarcinoma↗

PubMed2002

Diffusion weighted MR imaging in acute stroke: the SGH experience.

Cerebrovascular accident (CVA) is a leading cause of death and disability in many countries. Diffusion-weighted (DW) magnetic resonance (MR) imaging has been reported to be useful in the detection of acute strokes and as an investigative tool evaluating the therapeutic effects of neuroprotective and thrombolytic agents. The objectives of this study are to share our experience using the commercially available isotropic DW scan in imaging of acute stroke, assess its usefulness over conventional T2-weighted (T2W) scans in a busy clinical radiology unit and highlight it pitfalls. We found the rapid sub-minute DW technique well suited for ill and restless stroke patients and superior to T2W scans in many ways. It was highly sensitive to acute ischaemic lesions, made lesions easily identifiable and readily differentiated the acute lesion from a background of multiple chronic infarcts. However, there are potential pitfalls in the evaluation of small hyperacute posterior fossa strokes and venous infarcts. The major strength of this MR technique lies in its ability to diagnose hyperacute strokes and thence the potential for therapeutic thrombolysis, but unfortunately patients qualifying for the "therapeutic window" were a minority. More efforts need to be focused on public education in order for this powerful imaging modality to find its true value and contribute to viability of an effective thrombolytic programme.

Adult↗

PubMed2002

Update in the management of stroke.

Recent advances have improved the outlook for patients with stroke, Singapore's fourth leading cause of death. Stroke unit care reduces death, dependency and institutionalisation, independent of age, gender and stroke severity. Neuroimaging is essential prior to initiation of specific therapies. While computed tomography (CT) Head remains the most widely used modality, magnetic resonance imaging (MRI), particularly diffusion weighted imaging (DWI) has enhanced the positive diagnosis of ischaemic stroke. General medical measures include close monitoring, adequate oxygenation, avoidance of excessive blood pressure lowering, reduction of hyperthermia, control of hyperglycaemia, adequate nutrition, prevention of complications and early rehabilitation. Despite the risk of fatal intracranial haemorrhage, thrombolysis may improve outcomes in appropriately selected patients with ischaemic stroke. No safe and effective neuroprotectant has been found. While suboccipital craniectomy is established for large cerebellar infarcts and haemorrhage, surgical evacuation of supratentorial haemorrhage has not been shown to be beneficial. Hemicraniectomy reduces mortality after massive hemispheric ischemic stroke. Early and sustained antiplatelet use after atherothrombotic stroke reduces stroke recurrence. Stroke recurrence is also reduced by sustained warfarin use for cardioembolic stroke, carotid endarterectomy for severe symptomatic internal carotid artery stenosis, blood pressure lowering starting after the acute phase of stroke and lipid lowering. On-going clinical trails are likely to provide better treatments in the near future.

Aged↗

PubMed2001

Salvinorin C, a new neoclerodane diterpene from a bioactive fraction of the hallucinogenic Mexican mint Salvia divinorum.

Salvinorin C (1), a minor component from a biologically active TLC fraction, was isolated from the leaves of the Mexican mint Salvia divinorum. Its structure was elucidated on the basis of extensive proton and C-13 NMR experiments, as well as by comparison of the NMR data with those of the mono- and diacetate derivatives 5-7 of the major NaBH(4)-reduction product of salvinorin A (2). [structure: see text]

Diterpenes↗

PubMed2001

Molecular scanning of the human sorbin and SH3-domain-containing-1 (SORBS1) gene: positive association of the T228A polymorphism with obesity and type 2 diabetes.

In the mouse, the SH3P12 or the c-Cbl-associated protein (CAP) has been shown as an important signaling molecule in insulin-stimulated glucose uptake. The human homolog for the sorbin and SH3-domain-containing-1 gene, termed SORBS1, might play a role in human disorders with insulin resistance. To explore the genetic role of SORBS1 in human obesity and type 2 diabetes, we investigated the nucleotide polymorphisms in the SORBS1 gene with molecular scanning. After scanning for a total of 13,136 bp in each of 40 chromosomes, we have identified 14 single nucleotide polymorphisms (SNPs) in the human SORBS1 gene. Among them, two SNPs affected amino acid coding (R74W and T228A), four occurred within exons but did not affect amino acid coding, and the remaining eight occurred within introns, which were located outside of the consensus region of the splicing mechanism. Further studies in 202 non-obese, 113 obese and 455 subjects with type 2 diabetes revealed that the A-allele of the T228A polymorphism in exon 7 exerted a protective role for both obesity [relative risk 0.466; 95% confidence interval (95% CI) 0.265-0.821] and diabetes (relative risk 0.668; 95% CI 0.472-0.945). Neither allele of the R74W polymorphism was associated with either obesity or diabetes. In conclusion, our results suggest that the A228 allele of the T228A polymorphism of the SORBS1 gene is a protective factor for both obesity and diabetes, and also imply that the SORBS1 gene plays an important role in the pathogenesis of human disorders with insulin resistance.

Amino Acid Sequence↗

PubMed2001

Cloning, mapping, and characterization of the human sorbin and SH3 domain containing 1 (SORBS1) gene: a protein associated with c-Abl during insulin signaling in the hepatoma cell line Hep3B.

SH3P12/CAP/ponsin, a gene product with a sorbin homology domain and three consecutive SH3 domains in the carboxy-terminus, has been isolated from murine adipocytes and identified as an important adaptor during insulin signaling. Here we describe the cloning, mapping, and expression of the human homologue, termed SORBS1 (sorbin and SH3 domain containing 1). Multiple transcripts of this gene with different mRNA isoforms were observed among different tissues. Here we report 13 alternatively spliced exons, which were ascertained from the full-length cDNA cloned in adipose, liver, and skeletal muscle tissues. Among the major isoforms, the shortest, 2223-bp, open reading frame (ORF) encodes a protein with a predicted molecular weight of 81.5 kDa, while the longest, 3879-bp, ORF encodes a protein of about 142.2 kDa. This gene was mapped to human chromosome 10q23.3-q24.1, which is a candidate region for insulin resistance found in Pima Indians. In human hepatoma Hep3B cells, SORBS1 was partly dissociated from the insulin receptor complex and bound to c-Abl protein upon insulin stimulation. This interaction with c-Abl was through the third SH3 domain and a possible conformational change of SORBS1 induced by insulin. Our data suggest that c-Abl oncoprotein via SORBS1 might play a role in the insulin signaling pathway.

Amino Acid Sequence↗

PubMed2001

Quantification of L-ascorbic acid and total ascorbic acid in fruits and spinach by capillary zone electrophoresis.

A standard curve for the quantification of L-ascorbic acid (L-AA) by capillary zone electrophoresis (CZE) was established, and the quantification of ascorbic acid and total ascorbic acid in fruits (lemon, Sunkist, and pineapple) and spinach were performed using D-isoascorbic acid (D-IAA) as an internal standard. The minimum detection limits (MDLs) for L-AA and D-IAA were determined to be 1 and 2 microg/mL, respectively, at 265 nm. Dehydroascorbic acid (DHAA) in fruits and spinach was quantified in the presence of DL-homocysteine. The recoveries for L-AA in these juices were between 95 and 105%.

Ascorbic Acid↗

PubMed2001

Correlation of the apparent diffusion coefficient and the creatine level in early ischemic stroke: a comparison of different patterns by magnetic resonance.

It has been reported that reduction of the apparent diffusion coefficient (ADC) after stroke can persist for several days, after which the ADC increases gradually to an abnormally high level. We evaluated ADC values of stroke lesions and compared the results to the cellular density of the lesion by means of the creatine (Cre) level. This two-parameter estimation is of particular relevance in ascertaining the underlying cellular status. Lesion-to-contralateral ADC ratios (ADCn) were obtained based on diffusion-weighted echo-planar and fast spin-echo imaging. Single-voxel localized spectroscopy was used for quantification of cerebral metabolites in infarcted regions. Their levels were also compared to that in homotopic contralateral regions. Fifteen patients with ischemic stroke were examined at times ranging from 18-88 hours following the onset of symptoms. In the stroke lesion, there was a significant correlation between the ADC and the Cre level showing that the higher the cell density the lower the ADC value. For ADCn vs. the lesion Cre concentration and the lesion-to-contralateral Cre ratio (Cre(n)), the strengths of relationship were R2 = 0.70 and 0.58, respectively. It is concluded that ADC is a good reflection of cell density. Greatly lowered ADC values occur within the context of a stable cellularity. ADC and the Cre level have complementary roles in the characterization of stroke lesion with regard to the sequential stage.

Adult↗

PubMed2001

Axotomy along with hypoxia enhances the neuronal NADPH-d/NOS expression in lower brain stem motor neurons of adult rats.

This study was aimed to determine whether axotomy coupled with hypoxia would exert a more profound effect on injury-induced neuronal nitric oxide synthase (NOS) expression. In this connection, the vagus and the hypoglossal nerves of adult rats were transected unilaterally in the same animal, and half of the operated animals were subjected to hypoxia treatment. Both the neuronal NOS immunohistochemistry and the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry were used to assess the neuronal NOS expression. The present results have shown that the number of NADPH-d/NOS-positive [NADPH-d/NOS(1)] neurons in the hypoglossal nucleus (HN) peaked at 14 days after axotomy, while that in dorsal motor nucleus of vagus (DMN) and nucleus ambiguus (NA) was progressively increased up to 60 days. The up-regulation of NADPH-d/NOS in HN and DMN was more pronounced in hypoxic than in normoxic animals, a feature that was not evident in the NA. Quantitative analysis showed that the number of surviving motoneurons in normoxic animals was significantly higher than those subjected to hypoxia at 14 days postaxotomy in HN and at all postaxotomy time points in DMN. The difference may be attributed to their different functional components. Since O2 deprivation leads to poor cellular function, the stronger expression of NADPH-d/NOS and the more drastic neuronal loss following nerve transection in the hypoxic animals compared with the controls suggest that hypoxia plays an important role in peripheral neuropathies in which NO is implicated.

Animals↗