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Biomedical subjects

K C Tan

Publications and source records attributed to K C Tan.

At least 73 records · Page 4Linked to original sources
PubMed1999

Transpelvic rectus abdominis flap for perineal reconstruction following abdominal perineal resection with en bloc partial cystectomy and prostatectomy for locally advanced rectal cancer.

We report a case of locally advanced carcinoma of the rectum invading the bladder and prostate in a young man treated initially with neoadjuvant chemoradiotherapy. This was followed by an en bloc resection of the tumour, partial cystectomy and prostatectomy and an abdominal perineal resection. The urinary bladder was reconstructed and a new bladder neck reimplanted into the proximal urethra where the sphincter had been preserved. There was extensive radiation changes to the perineal skin where a wide excision had been performed. The pelvic defect was reconstructed with a pedicled transpelvic rectus abdominis myocutaneous flap. The patient recovered uneventfully and remains well with no clinical evidence of recurrence 18 months post-operatively. In very selected cases there is a definite role for neoadjuvant therapy and enbloc resection of the tumour followed by reconstruction of the perineum.

Adult↗
PubMed1998

Cutaneous manifestations of chronic arsenicism: review of seventeen cases.

BACKGROUND: Cutaneous complications arising from exposure to Chinese proprietary medicines known to contain inorganic arsenic have been rarely reported. OBJECTIVE: Our purpose was to study the nature, incidence, and sequelae of patients with chronic arsenicism and to review the literature on arsenic-induced skin diseases. METHODS: Case records of patients with cutaneous lesions related to chronic arsenicism seen from January 1990 to December 1996 were reviewed. Patients were interviewed and a complete skin and systemic examination was performed. Data on demography, history of arsenic ingestion, and type and distribution of skin lesions and visceral malignancy were collated. RESULTS: Seventeen Chinese patients (11 men, six women) were identified; their mean age was 64.5 years. Fourteen patients (82%) had exposure to Chinese proprietary medicines known to contain inorganic arsenic, and three had environmental arsenic exposure from well water. The mean age of these 14 patients was 17.6 years; mean duration of arsenic intake was 6.4 years. Seventeen patients had Bowen's disease; of these, 70% had 2 to 10 lesions. Of the 17 patients with arsenical keratoses on the palms, 76% had 2 to 10 lesions. Of the 14 patients (82%) with plantar arsenical keratoses, 64% had 11 to more than 50 lesions. Eleven patients (65%) had macular hypopigmentation. Seven patients (41%) had 11 squamous cell carcinomas (SCCs); three of the seven had more than one lesion. Fifty-five percent of SCCs arose from preexisting keratotic lesions (n = 4) or Bowen's disease (n = 2), and 45% arose de novo. One patient each (6%) had multiple basal cell carcinomas, laryngeal carcinoma, and metastatic SCC. The latency periods for the development of arsenical keratoses, Bowen's disease, and SCC were 28, 39, and 41 years, respectively. Patients with SCC were significantly older at the start of arsenic exposure and had significantly more palmar arsenical keratoses than those without SCC. CONCLUSION: Exposure to Chinese proprietary medicines containing inorganic arsenic poses a risk for the development of cutaneous and systemic malignancies. Long-term follow-up is necessary for tumor detection because of long latency periods. Surveillance programs are important to restrict the sale of Chinese proprietary medicines that may contain inorganic arsenic.

Aged↗
PubMed1998

M235T polymorphism of the angiotensinogen gene and hypertension in Chinese.

OBJECTIVES: To compare the distributions of the genotypes and alleles of the M235T polymorphism of the angiotensinogen gene for hypertensive patients and normotensive controls. DESIGN: A study of association of genetic polymorphisms. SETTING: An outpatient clinic run by a university department handling referrals from primary care. PATIENTS: Two hundred and four subjects, 103 normal controls and 101 patients with newly diagnosed or documented hypertension. METHOD: Genomic DNA was extracted from peripheral blood leucocytes, amplified by polymerase chain reaction and digested with the restriction enzyme Tth 111 I. Methionine (M) and threonine (T) alleles were identified after electrophoresis. MAIN OUTCOME MEASURES: Prevalences of angiotensinogen genotypes and alleles for hypertensive patients and controls. RESULTS: MM, TM and TT genotypes occurred in 3, 24 and 73% of controls and 1, 22 and 77% of hypertensive patients, respectively. The prevalences of the M and T alleles were 0.15 and 0.85 among controls and 0.12 and 0.88 among hypertensive patients. The prevalences of the angiotensinogen genotypes and alleles for controls and hypertensive patients did not differ significantly. CONCLUSIONS: Our findings differed from previous reports and suggested that this polymorphism is not associated with hypertension in this population.

Adult↗
PubMed1998

Decrease with age in frequency of the homozygous deletional angiotensin-converting enzyme genotype in hypertensive patients.

1. Angiotensin-converting enzyme (ACE) genotypes in hypertensive patients were studied in order to delineate their cardiovascular risk due to the ACE gene. We hypothesized that the distribution of ACE genotypes may change with age because of the risk of myocardial infarction associated with the homozygous deletional (DD) genotype. 2. A total of 223 subjects were recruited from the Hypertension Outpatient Clinic of the Sai Ying Pun Hospital with consent. They consisted of 75 patients with newly diagnosed or documented hypertension, 46 patients with ischaemic heart disease and 102 normal controls. Genomic DNA was extracted from peripheral leucocytes and amplified by polymerase chain reaction. Insertion (I) or deletion (D) alleles were identified after electrophoresis. The frequencies of ACE genotypes and alleles were measured in three age groups: < 50 years, 50-59 years and > or = 60 years. 3. A significant correlation between ACE genotype and age was found (P = 0.03). The relative frequency of the D allele in those under 50 years of age was similar in controls and hypertensive patients (0.40 vs 0.41; P = 0.94), but was significantly lower in patients > or = 50 years compared with those patients < 50 years of age (0.22 vs 0.41; P = 0.01). 4. The observed decrease in frequency of the DD genotype in older hypertensive patients is consistent with the increase in cardiovascular risk associated with the D allele and raises the possibility that the DD genotype may increase the risk of premature death, at least in the population studied.

Aging↗
PubMed1998

Plasma cholesteryl ester transfer protein activity in hyper- and hypothyroidism.

Thyroid dysfunction is associated with multiple changes in lipoprotein metabolism, and we have determined the effects of thyroid dysfunction on plasma cholesteryl ester transfer protein (CETP) activity. CETP is a plasma protein that mediates the exchange of cholesteryl ester and triglyceride between plasma lipoproteins and plays an important role in high-density lipoprotein metabolism and in the reverse cholesterol transport pathway. Plasma CETP activity was assayed in 18 hyperthyroid and in 17 hypothyroid patients, before and after treatment, by measuring the transfer of cholesteryl esters from exogenous radiolabeled high-density lipoprotein to apolipoprotein B-containing lipoproteins. Plasma CETP activity was increased in hyperthyroid patients, compared with their matched controls (22.11 +/- 8.92% transferred/5 microL.4 h vs. 16.75 +/- 6.48, P < 0.05), whereas in hypothyroid patients, plasma CETP activity was decreased (11.14 +/- 4.84% transferred/5 microL.4 h vs. 17.26 +/- 7.13, P < 0.01). Plasma CETP activity decreased after treatment of thyrotoxicosis, although a significant change was observed, mainly in the severely thyrotoxic patients with free T4 > 100 pmol/L (n = 11, 25.61 +/- 8.12% transferred/5 microL.4 h vs. 21.71 +/- 7.84, P < 0.05). In the hypothyroid patients, there was a significant increase in plasma CETP activity after thyroxine replacement (11.14 +/- 4.84% transferred/5 microL.4 h vs. 15.46 +/- 6.71, P < 0.01). There was a strong positive correlation between log(free T4) and plasma CETP activity (r = 0.51, P < 0.001). In summary, both hyper- and hypothyroidism are associated with significant changes in plasma CETP activity, and these changes are corrected when the patients have been rendered euthyroid.

Adult↗
PubMed1998

Effect of thyroid dysfunction on high-density lipoprotein subfraction metabolism: roles of hepatic lipase and cholesteryl ester transfer protein.

To investigate the effect of thyroid dysfunction on high-density lipoprotein (HDL) metabolism, we measured HDL subfractions, apolipoprotein A-I containing particles (LpA-I and LpA-I:A-II), and the activities of enzymes involved in the remodeling and metabolism of HDL [namely hepatic lipase (HL), lipoprotein lipase, and cholesteryl ester transfer protein (CETP)] in 18 hyperthyroid and 17 hypothyroid patients before and after treatment. HDL was subfractionated by density gradient ultracentrifugation, and LpA-I was analyzed by electroimmunodiffusion. The major changes were found in the HDL2 subfraction and in LpA-I particles. HDL2-C and LpA-I were reduced in hyperthyroidism (P < 0.01, P < 0.05, respectively) and increased in hypothyroidism (both P < 0.05) compared with their respective euthyroid matched controls. Changes in HDL2-cholesterol were reversed after treatment in both hyper- and hypothyroid patients, and LpA-I also decreased in the hypothyroid patients after treatment. HL (P < 0.05) and CETP activities (P < 0.05) were elevated in hyperthyroidism and reduced in hypothyroidism (P < 0.05, P < 0.01 respectively) and both were related to free T4 levels. The changes in HDL2-C and LpA-I correlated significantly with changes in HL after treatment but not with CETP or lipoprotein lipase. In summary, HDL metabolism was altered in thyroid dysfunction, and the effect of thyroid hormone on HDL was mediated mainly via its effect on HL activity.

Adult↗
PubMed1998

Effects of testosterone replacement on HDL subfractions and apolipoprotein A-I containing lipoproteins.

OBJECTIVES: Gonadal steroids are important regulators of lipoprotein metabolism. The aims of this study were to determine the effects of a minimum effective dose of testosterone replacement on high density lipoprotein (HDL) subfractions and apolipoprotein (apo) A-I containing particles (lipoprotein (Lp)A-I) and LpA-I:A-II) in hypogonadal men with primary testicular failure and to investigate the underlying mechanisms of these changes. MEASUREMENTS: Eleven Chinese hypogonadal men were started on testosterone enanthate 250 mg intramuscularly at 4-weekly intervals. HDL was subfractionated by density gradient ultracentrifugation and LpA-I was analysed by electro-immunodiffusion after 3, 6 and 12 weeks of treatment. Plasma cholesteryl ester transfer protein (CETP) activity and lipolytic enzymes activities in post-heparin plasma were measured to determine the mechanisms underlying testosterone-induced changes in HDL. RESULTS: The dosage of testosterone enanthate used in the present study resulted in suboptimal trough testosterone levels. No changes were seen in plasma total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C,) apo B and apo(a) after 12 weeks. There was a drop in HDL3-C compared to baseline (0.82 +/- 0.17 mmol/l vs. 0.93 +/- 0.13, P < 0.01) whereas a small but significant increase was seen in HDL2-C (0.21 +/- 0.13 mmol/l vs. 0.11 +/- 0.09, P < 0.05). Plasma apo A-I decreased after treatment (1.34 +/- 0.25 g/l vs. 1.50 +/- 0.29, P < 0.01), due to a reduction in LpA-I:A-II particles (0.86 +/- 0.18 g/l vs. 0.99 +/- 0.24, P < 0.01). No changes were observed in the levels of LpA-I particles. No significant changes were seen in plasma CETP and lipoprotein lipase activities after testosterone replacement but there was a transient increase in hepatic lipase (HL) activity at weeks 3 and 6. The decrease in HDL correlated with the increase in HL activity (r = 0.62, P < 0.05). CONCLUSIONS: Testosterone replacement in the form of parenteral testosterone ester given 4-weekly, although unphysiological, was not associated with unfavourable changes in lipid profiles. The reduction in HDL was mainly in HDL3-C and in LpA-I:A-II particles and not in the more anti-atherogenic HDL2 and LpA-I particles. The changes in HDL subclasses were mainly mediated through the effect of testosterone on hepatic lipase activity.

Adult↗
PubMed1998

Liver transplant in Singapore--coming of age.

BACKGROUND/AIM OF STUDY: Liver transplantation was first performed in 1967, and has become an accepted form of treatment worldwide for chronic liver diseases, acute liver failure and certain metabolic diseases. We document our experience in Singapore over the last 7 years since the first transplant was performed in 1990. METHOD: Retrospective study at National University Hospital, Singapore. RESULTS: Twenty-two operations (10 paediatric and 12 adults) have been performed with the last 17 having been performed in the last 17 months. Currently, there are 15 survivors (68%) since 1990, and percentage survival is even better if one considers the cases from the last 17 months when the majority of cases (17 transplants-77%) were performed (77% survival). The most common indication for transplant was biliary atresia for the paediatric group, while the adults were transplanted for hepatitis B and C cirrhosis, primary biliary cirrhosis, and fulminant liver failure. Tacrolimus is the main immunosuppression (10 patients), with the remaining 5 patients on cyclosporine. Various surgical techniques (living donor, graft reduction) have been employed successfully to provide a complete transplant service. Hospital and ICU stays are within normal limits and the hospital charges range from a low of S$30,000 to S$141,000. CONCLUSION: Liver transplantation has become a reality in Singapore with outcomes comparable to other transplant centres. The shortage of donors remains the greatest stumbling block for further expansion.

Adolescent↗
PubMed1998

Soft tissue cover in compound and complicated tibial fractures using microvascular flaps.

This is a retrospective review of the use of microvascular flaps in the salvage of severely injured lower limb. From January 1992 to December 1994, we treated 10 patients using 10 microvascular flaps; 8 patients with Type III compound tibial fractures and 2 patients with infected implants following internal fixation of comminuted tibial fractures. The size of soft tissue defect ranged from 6 x 3 cm to 20 x 10 cm. One patient had a 6 cm bony defect. Soft tissue cover was achieved in 9 patients using microvascular muscle flaps with meshed split skin grafts and 1 patient using a scapula osteocutaneous flap. They were performed within 5 to 27 days following injury or removal of implants (mean 18 days). All the microvascular flaps were successful (100%). One re-exploration was performed. The mean period of hospitalization following microsurgical flap cover was 16.8 days. Eight out of 10 patients were followed up for a mean period of 48 months. All the 8 lower limbs were successfully salvaged. Three out of 8 patients (37.5%) had chronic osteomyelitis which required sequestrectomy and bone grafting. No amputation was necessary. Two patients required adjunctive cancellous bone grafting to accelerate bony union. Six out of 8 patients (75%) achieved bony union and full weight bearing capacity. The use of microvascular flap in achieving soft tissue cover plays an important role in the salvage of severely traumatized lower limb. Microvascular muscle flap is preferred when only soft tissue defect is present. Successful soft tissue cover facilitates secondary bone grafting procedures. Although the timing of surgery per se does not adversely affect the success rate of microvascular flaps, delayed soft tissue cover is associated with a high chronic infection rate (37.5%). An adequate surgical debridement is crucial in reducing the complication of deep infection.

Adult↗
PubMed1997

Phylogenetic analysis of the human papillomavirus type 2 (HPV-2), HPV-27, and HPV-57 group, which is associated with common warts.

Human papillomavirus types 2 (HPV-2), HPV-27, and HPV-57, are three closely related viruses within the phylogenetic supergroup formed by the remotely related genital papillomaviruses. In contrast to this phylogenetic association, these three viruses are most often found in common warts at nongenital sites, but also occasionally in genital warts and mucosal lesions of the nasopharyngeal cavity. We studied the genomic diversity of HPV sequences in skin warts presumably caused by these viruses. These biopsies were sampled from 75 patients living in Germany, Japan, or Singapore. Among 27 warts with HPV-2, we found seven new genomic variants and among 32 with HPV-57, eight new variants. In both cases, we did not detect the original prototype genomes. In contrast, 13 of 16 warts with HPV-27 contained the prototype genome, and only one new variant was found in three patients. We did not find variants clearly intermediate between any two types, although HPV-2 and HPV-27 are among the most closely related of the extent HPV types. We also did not detect novel HPV types, although the samples were examined with polymerase chain reaction protocols that would have detected remotely related HPVs. So we propose that the phylogenetic group formed by HPV-2, HPV-27, and HPV-57 has no or only very are additional members. One of the HPV-57 variants found, HPV-57-G44, was most likely identical to the subtype HPV-57b, previously proposed to be associated with nasal neoplasia, but found here frequently in common skin warts. Our publication establishes a foundation for pathological and phylogenetic comparisons of HPV types in skin warts.

Base Sequence↗
PubMed1997

LDL subfractions in acromegaly: relation to growth hormone and insulin-like growth factor-I.

Acromegaly is associated with changes in lipoprotein metabolism and an excess in cardiovascular mortality. We have examined low density lipoprotein (LDL) subfraction distribution in 24 patients with active acromegaly and in controls matched for age, sex and body mass index. LDL was subfractionated by density gradient ultracentrifugation. The concentration of small dense LDL-III was significantly higher in the acromegalic patients compared to the controls (94.2 +/- 44.9 versus 67.2 +/- 30.4 mg/dl, P < 0.05) and there was a concomitant reduction in the intermediate subfraction LDL-II (124.8 +/- 31.3 versus 149.9 +/- 30.0 mg/dl, P < 0.05). Univariate analysis showed that both growth hormone (GH) and insulin-like growth factor (IGF)-I correlated with LDL-III and inversely with LDL-II. Acromegalic patients were found to have lower hepatic lipase (HL) and lipoprotein lipase (LPL) activities than controls (HL: 13.29 +/- 6.56 versus 21.58 +/- 7.27 micromol FFA released/ml/h, P < 0.001: LPL: 7.22 +/- 3.04 versus 11.53 +/- 7.85 micromol FFA released/ml/h, P < 0.05) whereas plasma cholesteryl ester transfer protein (CETP) activity was significantly increased (8.15 +/- 1.81 versus 5.54 +/- 1.86 pmol/microl/h, P < 0.001). Both GH and IGF-I were significantly associated with HL, LPL and CETP activities. Multivariate analysis on this relatively small sample size showed that in normal subjects, triglyceride and HL activity were the major determinants of LDL-III. In contrast, GH and HDL were the main determinants in acromegaly, accounting for 32 and 24% in the variability of LDL-III respectively. In conclusion, GH excess has a direct effect on LDL subfraction distribution.

Acromegaly↗
PubMed1996

Unusual endocrine presentations of nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma is endemic in Southern China and the majority of patients present with local symptoms due to the tumor. METHODS: This report describes two unusual cases of occult nasopharyngeal carcinoma in which the patients initially presented with endocrine manifestations. RESULTS: The first patient presented with Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) production. Nasolaryngoscopy showed a growth in the left nasal fossa and biopsy revealed a poorly differentiated nasopharyngeal carcinoma that exhibited positive immunostaining for ACTH. The second patient presented with a 10-month history of bone pain over both lower limbs. She was normocalcemic but her serum alkaline phosphatase was markedly elevated. A bone biopsy showed both osteoclastic and osteoblastic activity with widespread fibrosis suggestive of Paget's disease. Three months later, she developed third cranial nerve palsy. Computed tomography investigation revealed a soft tissue mass filling the sphenoid and ethmoid sinuses. Biopsy showed a poorly differentiated nasopharyngeal carcinoma. The bone biopsy was reviewed and immunohistochemistry demonstrated the presence of cells positive for the epithelial marker AE1/3 within the fibrous stroma. Radio-labeled in situ hybridization showed that Epstein-Barr virus early RNA was present in these tumor cells and the bone lesions were in fact metastases. CONCLUSIONS: Nasopharyngeal carcinoma can present with rather atypical symptoms that may lead to a delay in diagnosis. Therefore, in high risk populations, it is important to consider nasopharyngeal carcinoma as a possible primary tumor in patients with occult carcinomas.

ACTH Syndrome, Ectopic↗
PubMed1996

Postprandial lipid metabolism and beta-cell function in non-insulin-dependent (type 2) diabetes mellitus after a mixed meal with a high fat content.

Postprandial lipid profiles and release of insulin (INS), intact proinsulin (PI), and 32-33 split proinsulin (SPI) in response to a mixed meal with a high fat content were determined over a 12 h period in non-obese control subjects (n = 10) and non-insulin-dependent (Type 2) diabetic (NIDDM) patients with normotriglyceridaemia (NTG; n = 11) and hypertriglyceridaemia (HTG; n = 10), by calculation of the 'areas under the curves' (AUC). The postprandial triglyceride-AUC was significantly greater in HTG-NIDDM patients (p < 0.05) than in NTG-NIDDM or control subjects. Chylomicron clearance was impaired only in HTG-NIDDM patients (p < 0.05). Chylomicron-remnant clearance was impaired in both groups of NIDDM patients (p < 0.05). The postprandial suppression of plasma non-esterified fatty acid (NEFA) content was impaired in HTG-NIDDM patients (p < 0.05). The postprandial INS-, PI- and SPI-AUCS were significantly greater than in the control subjects (p < 0.05). In NIDDM, triglyceride-AUC correlated significantly with PI and SPI release (triglyceride-AUC vs PI, p < 0.05; triglyceride-AUC vs SPI, p < 0.01). Chylomicron AUC was unrelated to the fasting plasma INS, PI or SPI content, unlike chylomicron-remnant-AUC (Chylomicron-remnant-AUC vs INS, p = NS; chylomicron-remnant-AUC vs PI, p < 0.01; chylomicron-remnant-AUC vs SPI, p < 0.01). The NEFA response was associated with fasting plasma SPI content (NEFA-AUC vs SPI, p < 0.05). Postprandial chylomicron AUC was not related to the overall secretion of INS, PI or SPI. However, triglyceride-, chylomicron-remnant- and NEFA-AUCs were all associated positively with the release of PI and SPI (p < 0.05). In multivariate analyses, chylomicron-remnant clearance had the major relationship with the release of insulin precursors, accounting for 23% of the variability (p < 0.01). Inclusion of overall response of free fatty acids improved the model, with both parameters together accounting for 30% of the variability (p < 0.01). The output of the beta-cell over the postprandial period differed between the NIDDM patients and the control subjects in that when glycaemic stimulation was moderate, the proportion of insulin-like molecules as a percentage of the total output was greater than in control subjects but this was not the situation when glycaemia was greatest. We conclude that abnormal postprandial lipaemia in NIDDM is associated with beta-cell output, possibly mediated by the availability of free fatty acids.

Blood Glucose↗
PubMed1996

Glycine substitutions in the triple-helical region of type VII collagen result in a spectrum of dystrophic epidermolysis bullosa phenotypes and patterns of inheritance.

The dystrophic forms of epidermolysis bullosa (DEB) are characterized by fragility of the skin and mucous membranes. DEB can be inherited in either an autosomal dominant or autosomal recessive pattern, and the spectrum of clinical severity is highly variable. The unifying diagnostic hallmark of DEB is abnormalities in the anchoring fibrils, which consist of type VII collagen, and, recently, mutations in the corresponding gene, COL7A1, have been disclosed in a number of families. In this study, we report six families with glycine substitution mutations in the triple-helical region of type VII collagen. Among the six families, two demonstrated a mild phenotype, and the inheritance of the mutation was consistent with the dominantly inherited form of DEB. In the four other families, the mutation was silent in the heterozygous state but, when present in the homozygous state, or combined with a second mutation, resulted in a recessively inherited DEB phenotype. Type VII collagen is, therefore, unique among the collagen genes, in that different glycine substitutions can be either silent in heterozygous individuals or result in a dominantly inherited DEB. Inspection of the locations of the glycine substitutions along the COL7A1 polypeptide suggests that the consequences of these mutations, in terms of phenotype and pattern of inheritance, are position independent.

Adult↗