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Biomedical subjects

G S Hong

Publications and source records attributed to G S Hong.

At least 19 recordsLinked to original sources

Acoustic diagnosis of aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Phonocardiography is a promising non-invasive diagnostic tool for the assessment of aortic stenosis (AS), and time-frequency representation is a potential tool to extract information from the phonocardiogram (PCG) signal. The study aim was to develop an acoustical method to predict the severity of AS. METHODS: Normalized continuous wavelet transform (NCWT) and fast Fourier Transform (FFT) were used to perform a spectral analysis of the PCG signal. A multi-peak detection algorithm was developed to determine the dominant frequency (DF) of systolic murmurs (SM). The spectral ratio of the SM, integration of the NCWT of SM (SI), and combined information of SM and second heart sound, were also calculated. RESULTS: The DF correlated best with the hemodynamic data: r = -0.72 with aortic valve (AV) area; r = 0.63 with maximal blood velocity through the AV; and r = 0.57 with mean pressure gradient across the AV. Based on DF and SI data, the study subjects (n = 59) were classified into three categories: severe AS; moderate AS; and other cases. The acoustical and echo classifications were in agreement in 50 subjects (85%). CONCLUSION: The acoustical method developed cannot predict accurately the severity of AS, but is valuable when conducting a screening classification before an invasive method is used.

Aged↗

Founder mutation in the BRCA1 gene in Malay breast cancer patients from Singapore.

The mutation spectrum of the BRCA1 gene among ethnic groups from Asia has not been well studied. We investigated the frequency of mutations in the BRCA1 gene among Malay breast cancer patients from Singapore, independent of family history. By using the protein truncation test (PTT) and direct sequencing, BRCA1 mutations were detected in 6 of 49 (12.2%) unrelated patients. Four novel missense mutations in exon 11, T557A (1788A>G), T582A (1863A>G), N656S (2086A>G) and P684S (2169C>T) were identified in one patient. Two patients had missense mutations in exon 23, V1809A (5545T>C), which has been previously detected in individuals from Central and Eastern Europe. Three unrelated patients had the deleterious 2846insA frameshift mutation in exon 11. Methylation specific PCR (MSP) of the promoter region of the BRCA1 gene detected hypermethylation of tumor DNA in an additional 2 patients. Haplotype analysis using the microsatellite markers D17S855, D17S1323 and D17S1325 revealed a common haplotype for the three unrelated patients and their three relatives with the 2846insA mutation. These findings strongly suggest that the 2846insA mutation, the most common deleterious mutation in this study, may possibly be a founder mutation in breast cancer patients of Malay ethnic background.

Adult↗

Well-differentiated thyroid carcinoma: factors predicting recurrence and survival.

AIMS: 1) Determine the patient and tumour characteristics for well-differentiated thyroid carcinoma--towards developing a unique risk classification for our largely Chinese population. 2) Assess extent of thyroid surgery required. 3) Document prognostic value of UICC and AMES classification. METHODS: Retrospective review of 175 patients treated for primary thyroid epithelial malignancy by the Department of General Surgery at the Singapore General Hospital. RESULTS: There were 78% papillary carcinomas (PC) and 19% follicular carcinomas (FC). Female: male ratio was 3:1. Patient distribution in the UICC stages I, II, III, IV is respectively 56, 11, 31 and 2%. Twenty-six percent had hemithyroidectomy, and 74% total thyroidectomy. Neck dissections were required in 6% of FC compared to 34% of PC. Mean follow-up was 40 months. Extent of surgery did not affect PC/FC survival nor recurrence rates (p=0.53 and 0.06 respectively). Recurrences occurred in 15% FC and 9% PC. Death occurred in one FC and two PC. Survival correlated with UICC stage I/II and stage III/IV groups (p=0.04), and recurrence correlated with AMES High and Low Risk groups (p=0.004). No statistically significant difference was shown for survival between PC and FC or AMES groups and recurrence between PC and FC or UICC groups. CONCLUSIONS: Extent of thyroid surgery does not significantly affect local recurrences of PC/FC. The characterisation of thyroid carcinoma here is an important step towards developing a risk classification unique to our largely Chinese population.

Adenocarcinoma, Follicular↗

FLASH coordinates NF-kappa B activity via TRAF2.

FLASH is a protein recently shown to interact with the death effector domain of caspase-8 and is likely to be a component of the death-inducing signaling complex in receptor-mediated apoptosis. Here we show that antisense oligonucleotide-induced inhibition of FLASH expression abolished TNF-alpha-induced activation of NF-kappaB in HEK293 cells, as determined by luciferase reporter gene expression driven by a NF-kappaB responsive promoter. Conversely, overexpression of FLASH dose-dependently activated NF-kappaB, an effect suppressed by dominant negative mutants of TRAF2, NIK, and IKKalpha, and partially by those of TRAF5 and TRAF6. TRAF2 was co-immunoprecipitated with FLASH from the cell extracts of HEK293 cells or HeLa cells stably expressing exogenous FLASH (HeLa/HA-FLASH). Furthermore, serial deletion mapping demonstrated that a domain spanning the residues 856-1191 of FLASH activated NF-kappaB as efficiently as the full-length and could directly bind to TRAF2 in vitro and in the transfected cells. Taken together, these results suggest that FLASH coordinates downstream NF-kappaB activity via a TRAF2-dependent pathway in the TNF-alpha signaling.

Animals↗

Genotoxicity of human breast milk from different countries.

Dietary and/or environmental factors appear to play a key role in the international variations that exist in breast cancer incidence. The genotoxicity of breast milk extracts is being examined as a possible indicator of in vivo exposure of mammary epithelial cells to DNA-damaging agents. Breast milk samples were obtained from the UK (n = 32), a high risk country, and from Hong Kong (n = 10), India (n = 20) and Singapore (n = 20), countries of lower breast cancer incidence. The abilities of breast milk extracts to induce DNA damage detected as single-strand breaks (SSBs) in the alkaline Comet assay and to induce micronuclei in MCL-5 cells and mutations in Salmonella typhimurium YG1019 were investigated. In the Comet assay 18 of 32 (56%) UK samples induced significant increases in DNA SSBs compared with 2 of 10 (20%), 5 of 20 (25%) and 8 of 20 (40%) of the samples from Hong Kong, India and Singapore, respectively. The proportion of positive samples was significantly higher in the UK group than in the combined low breast cancer incidence group and significantly higher than in the Indian group (P < 0.05, Fisher's exact test). In the micronucleus assay 9 of 32 (28%) UK samples showed significant activity compared with 0 of 10 (0%), 2 of 20 (10%) and 3 of 20 (15%) of the samples from Hong Kong, India and Singapore, respectively. Extracts of all the aforementioned milk samples were also tested for bacterial mutagenicity. Nine of 32 (28%) UK samples induced significant activity with a dose-response effect. Although activity was detected in samples from the other countries, comparable dose-response data could not be obtained because of a lack of material. This pilot study suggests that genotoxic components occur more frequently in UK breast milk than in milk from some other countries with a lower incidence of cancer. More work is required to confirm these initial findings and to examine their relevance to variations in breast cancer incidence.

Comet Assay↗

A case of alpha-fetoprotein-producing gastric cancer.

INTRODUCTION: A case of alpha-fetoprotein (AFP)-producing gastric cancer is described in a 57-year-old Chinese woman. CLINICAL PICTURE: She presented with bleeding tendency and bone pain, and was found to have haematological evidence of disseminated intravascular coagulation and spinal metastasis. Her tumour markers, including AFP, Ca 19-9 and carcinoembryonic antigen (CEA) were elevated. In view of the elevated tumour markers, there was an exhaustive search for a primary lesion in the gastrointestinal tract, liver and ovaries. There was no radiological evidence to suggest any lesion in the chest, liver or pelvis. Lectin affinity electrophoresis of the AFP showed AFP-L2 and AFP-L3 bands, which are suggestive of a non-hepatoma malignancy. MANAGEMENT: Gastroscopy showed a gastric ulcer and she developed bleeding after the gastric biopsy which required urgent surgery. Intraoperatively she was found to have carcinomatous peritone and a malignant ulcer in the greater curve of the stomach. Histology confirmed a linitis plastica like adenocarcinoma which stains for AFP. OUTCOME: She died from multi-organ failure 3 days after surgery. CONCLUSION: AFP-producing adenocarcinoma of the stomach is not uncommon. Lectin affinity electrophoresis of AFP is helpful in the differentiation between hepatoma and non-hepatoma malignancies.

Adenocarcinoma↗

Reconstitution of caspase-8 sensitizes JB6 cells to TRAIL.

TRAIL induces apoptosis in various tumor cells. We report here that caspase-8 is required in TRAIL-induced cell death. Western blot analyses and enzyme assays showed that exposing Jurkat cells to TRAIL resulted in activation of caspases-8 followed by caspase-3 and -9. Acetyl-IETD-fluoromethylketone, a caspase-8 inhibitor, potently suppressed TRAIL-induced cell death compared to acetyl-DEVD-fluoromethylketone and acetyl-LEHD-fluoromethylketone, inhibitors of caspase-3 and caspase-9, respectively. JB6 cells, a caspase-8-deficient Jurkat variant, were completely resistant to TRAIL. However, reconstitution with a caspase-8, but not with caspase-2 or -3, sensitized JB6 cells to subsequent exposure to TRAIL. These results are indicative of the crucial function of caspase-8 in TRAIL-induced apoptosis in Jurkat cells.

Apoptosis↗

Management of intraparotid facial nerve schwannomas.

BACKGROUND: The purpose of the present paper was to review the management of intraparotid facial nerve schwannoma so as to discuss its clinical presentation, evaluate the various possible diagnostic investigations, and compare the various surgical options and outcome. METHODS: Case series was undertaken of five (1.3%) patients with facial nerve schwannoma out of 400 consecutive parotidectomies at Singapore General Hospital. RESULTS: There were three men and two women with an age range of 29-65 years. Three patients presented with painless parotid lumps while two had painful parotid swellings. None had facial nerve paresis. Only one patient had preoperative diagnosis suspicious of schwannoma by fine-needle aspiration cytology (FNAC). Diagnoses were made intraoperatively. Four patients had excision with cable grafting of the nerve defect. achieving facial nerve grade II-IV (House-Brackmann scale). One patient who underwent enucleation of tumour with nerve preservation achieved grade II. CONCLUSIONS: Preoperative diagnosis is difficult but it is important for discussion of the extent and options of surgery. Fine-needle aspiration cytology holds promise in making a preoperative diagnosis. Enucleation with nerve preservation where possible seems to offer better facial function whereas nerve excision with cable graft can give satisfactory results.

Adult↗

Epidemiology of Warthin's tumour of the parotid gland in an Asian population.

BACKGROUND: Recent studies have documented a number of changing demographic features in the occurrence of Warthin's tumour (adenolymphoma) of the parotid gland. In order to analyse its epidemiology in an Asian population, a retrospective study was performed on all parotid neoplasms (n = 289) operated on between 1988 and 1998. PATIENTS AND METHODS: A total of 209 consecutive patients were selected for study, 136 with pleomorphic adenomas (one bilateral) and 73 with Warthin's tumours (seven bilateral). Patients were analysed with regard to tumour incidence, age, sex and race. Smoking as an aetiological factor in the development of Warthin's tumour was also studied. RESULTS: Warthin's tumour formed 25 per cent of parotid tumours and its ratio to pleomorphic adenomas was 1 : 1.9. Multicentricity was found in 14 patients (19 per cent). The male : female ratio for Warthin's tumours was 4.6 : 1. The proportion of Warthin's tumours did not show any increasing trend relative to pleomorphic adenomas. The racial distribution of Warthin's tumours showed an increased incidence among Chinese and a reduced incidence among Malays and Indians. The adjusted odds ratio for sex and age favouring an association between smoking and Warthin's tumour was 39.5 (95 per cent confidence interval 10.5-149. 0; P < 0.0001). CONCLUSION: The incidence of Warthin's tumour is considerable among Asians although there is still male predominance. There is no rising incidence of Warthin's tumour; the trend parallels the declining smoking rate in the population. The lower incidence among ethnic groups with dark skin seems to suggest concomitant genetic factors other than environmental factors alone in histogenesis. Smokers have a 40-fold greater risk than non-smokers of developing a Warthin's tumour.

Adenolymphoma↗

Splenic angiosarcoma--an unusual cause of bleeding gastrointestinal tract.

Splenic angiosarcoma is a rare malignant vascular tumour with about 100 reported cases to date. The presentation of splenic angiosarcoma is highly variable, frequently causing diagnostic difficulty. It usually presents with splenomegaly, abdominal pain and occasionally with a microangiopathic type of anaemia. Here we report an additional case of primary angiosarcoma of the spleen presenting as a problem of bleeding from the gastrointestinal tract.

Gastrointestinal Hemorrhage↗

Primary reconstruction after extensive chest wall resection.

BACKGROUND: Chest wall resection and reconstruction has been proven to be a safe surgical procedure. This is particularly useful for breast cancer patients with chest wall recurrences or for those who first present with locally advanced cancer in the chest wall where there is both a large soft tissue and bony defect that need repair. In addition, many of these patients have had irradiation or chemotherapy, which can significantly impair wound healing. METHODS: Thirty-four patients underwent chest wall resection and primary reconstruction over an 8-year period. RESULTS: Twenty-three patients had breast carcinomas and six had breast and chest wall sarcomas. Of the breast carcinoma patients, 12 had local recurrences and 11 presented with locally advanced primary disease. Bony resection of the chest wall was required in 16 (47%) cases. Thirty myocutaneous flaps (18 rectus abdominis, four pectoralis major, eight latissimus dorsi) and three omental flaps were used for reconstruction. One required a deltovertebral skin flap. Skeletal reconstruction was necessary in four cases. All except one (97%) achieved primary wound healing. There was one mortality (3%) and three patients required further surgery for complications that were related to the reconstruction. Post-resection metastases occurred in 13 (42%) patients and only 2 (6%) had local recurrences. The 2-year survival rate was 78% with a mean survival time of 25.5 months. CONCLUSIONS: Primary reconstruction for curative or palliative purposes is a useful and safe surgical procedure for patients with recurrent or locally advanced chest malignancies after extensive chest wall resection. Pedicled myocutaneous flap is the preferred option for skeletal and soft-tissue coverage.

Bone Neoplasms↗

Flexible endoscopic tracheo-oesophageal puncture under local anaesthetic.

Blom-Singer valve prosthesis is an increasingly popular technique for voice rehabilitation in alaryngeal patients. Although primary voice puncture is being practised, the creation of the tracheo-oesophageal fistula is performed in the majority of patients as a secondary procedure. We describe a technique of secondary tracheo-oesophageal puncture using the flexible endoscope which can be performed under local anaesthetic and sedation. The technique overcomes the difficulty of passing a rigid oesophagoscope or forceps to the level of the tracheostome in a scarred and irradiated neck. The new technique also obviates the need for general anaesthesia. We have successfully used the technique in three patients.

Anesthesia, Local↗

Primary reconstruction after chest wall resection in breast cancer.

Breast cancer patients with chest wall recurrence or patients with advanced breast cancer pose a difficult challenge to surgeons. Surgical ablation results in not only a large soft tissue defect that needs cover but often, in addition, a significant bony chest wall defect. The majority of these patients would have already received irradiation or chemotherapy or both. Thus, wound healing is significantly impaired. For these reasons, surgery was previously not attractive as an alternative in the palliation of these patients. Over a one-year period, seven breast cancer patients had chest wall resection. Six patients had recurrent tumours and one had advanced primary breast cancer. Two of these patients required only extensive resection of soft tissue of the anterior chest wall. The other five patients required, in addition, resection of the bony chest wall. Myocutaneous flaps were used to repair the surgical defects in six of these patients. Five were rectus abdominis myocutaneous flaps and one a pectoralis major myocutaneous flap. In one patient, a deltovertebral skin flap, which is an axial pattern skin flap was used. Primary wound healing was achieved in five of six patients (83%). One patient died immediately post-operatively, the cause of which is unknown. One of the rectus abdominis flap needed an exploration but was ultimately salvaged. This paper demonstrates the usefulness of the myocutaneous flap in enabling surgery to become a modality for palliation of patients with recurrent and advanced breast cancer.

Adult↗

Oestrogen receptors in well differentiated thyroid cancers.

Oestrogen receptor (ER) monoclonal antibody, H222 was used to study ER expression in forty-seven paraffin embedded blocks of well differentiated thyroid cancers. Trypsinisation, DNase I digestion, together with the use of labelled streptavidin biotin immuno-histochemical staining kit were adopted to increase the sensitivity of the immunoreaction. One out of twenty-seven papillary carcinomas and one out of twenty follicular carcinomas were immunoreactive. Thus, 4.3% of the well differentiated thyroid cancers were noted to express ER. The increased incidence and the better prognosis in females with well differentiated thyroid cancers is unlikely to be explained on the presence or absence of ER.

Adenocarcinoma↗

Dieulafoy's disease: cause of massive upper gastrointestinal haemorrhage in two Asian women.

Dieulafoy's disease is a submucous arterial malformation of the stomach, and is a known cause of massive upper gastrointestinal bleeding. To date, 125 cases have been reported in the literature. Fatality is high if the condition remains undiagnosed. Endoscopy is difficult but important in the diagnosis of Dieulafoy's disease. Dieulafoy's disease in two Asian women are reported here. Both required large amount of blood transfusions as the diagnosis was not recognised early. Greater awareness of the condition will enable earlier diagnosis and reduced mortality from this condition.

Adult↗

Protective effect of aprotinin on ischemic hepatocellular damage.

During hepatic resection, occlusion of the hepatoduodenal ligament has been frequently applied to prevent intraoperative bleeding. To reduce hepatocellular ischemic damage in this procedure, we pretreated animals with Aprotinin. Three hours after an intravenous injection of 40,000 KIU Aprotinin in SD rats, we occluded the afferent hepatic vessels for 50-min and 60-min periods. 92% of occluded animals could sustain life after 60 min. Without premedication only 17 of 25 animals (68%) survived the 50-min occlusion, and 18 of 32 (56%) the 60-min occlusion. Biochemical analysis of sera was carried out 12 hr after a 40- and 60-min occlusion of the hepatoduodenal ligament with Aprotinin pretreatment. Furthermore we induced compensatory cirrhosis by application of CCL4 and biochemical analysis of sera was carried out after a 30-min occlusion. The elevation of SGOT and SGPT values was drastically reduced in the animals with Aprotinin medication in comparison with those without treatment. These observations suggest the highly protective effect of Aprotinin in the case of warm ischemic hepatic damage, especially in the cirrhotic liver. After pretreatment of LEW rats with Aprotinin (40,000 KIU i.v.), we perfused the livers with chilled Ringer solution containing 40,000 KIU Aprotinin/20 ml. We transplanted the livers orthotopically into LEW rats. With the application of Aprotinin liver preservation time increased to 10-15 hr. However, without Aprotinin the livers could be successfully preserved for only 4-6 hr. Our results indicated that premedication with high doses of Aprotinin provided highly protective effects against warm and cold ischemic damage of the liver.

Animals↗

Bacterial and mycotic otological infections in Singapore.

This paper describes a microbiological study of 84 young adult men with clinical otitic infections. Gram-negative aerobic bacilli were frequently isolated from these patients diagnosed as having otitis externa or chronic suppurative otitis media, of which Pseudomonas species predominated. Staphylococcus aureus, S. epidermidis and aerobic Corynebacterium species (diphtheroids) were also found. About 40% of ear infections were attributed to otomycoses, chiefly from Aspergillus species and Candida parapsilosis. Antimicrobial susceptibility testing of the bacterial isolates revealed that Pseudomonas species were generally resistant to antibiotics commonly employed in general practice: ampicillin, erythromycin, co-trimoxazole, tetracycline and cephaloridine. However, polymyxin B, gentamicin and neomycin were active against some Pseudomonas isolates. Other Gram-negative bacilli were also mainly sensitive to gentamicin, neomycin as well as co-trimoxazole. Disc diffusion and minimum inhibitory concentration studies demonstrated good activity of ceftazidime, cefoperazone, tobramycin and carbenicillin against strains of Pseudomonas species and other Gram-negative rods. Cefotaxime and cefoxitin were active against Gram-negative bacilli other than Pseudomonas species. Beta-lactamase production did not appear to be the main mechanism of resistance in these community-acquired Gram-negative bacillary isolates. The antimicrobial therapy of otological infections is reviewed.

Adult↗