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Biomedical subjects

K C Loh

Publications and source records attributed to K C Loh.

At least 19 recordsLinked to original sources

Controversial endocrine interventions for the aged.

Specific endocrine changes occur with the ageing process. The last decade has witnessed significant progress in the basic and clinical science of ageing, thereby rejuvenating the interest in anti-ageing medicine, especially that of hormone replacement, by medical professionals and the lay public. However, endocrine manipulation as a therapeutic strategy for ageing is still evolving as continuing research attempts to answer the many questions of what it can achieve at the risk of incurring unknown long-term adverse effects. The current day doctor is confronted with a host of options, and will benefit from a synopsis of the latest evidence before making the most appropriate decision for aged patients seeking hormonal replacement therapy as a means to counter the effects of ageing. This review aims to give a rapid overview of the endocrine profile of geriatric population and the studies on the more controversial hormonal replacement therapies for the aged.

Aged↗

Thyrotoxic periodic paralysis complicated by near-fatal ventricular arrhythmias.

A 35-year-old Chinese man presented with acute thyrotoxic periodic paralysis complicated by near-fatal cardiac arrhythmias due to persistent hypokalaemia, despite maximum potassium supplementation. He was eventually resuscitated with external cadioversion. In this unusual case of severe refractory hypokalaemia leading to ventricular fibrillation in a patient with underlying thyrotoxicosis, the potential dangers concerning the use of dextrose infusion and beta-adrenergic agent for resuscitation are highlighted.

Adult↗

Accidental provocation of phaeochromocytoma: the forgotten hazard of metoclopramide?

The perilous potential of metoclopramide when used inadvertently in patients harbouring phaeochromocytomas goes largely under-recognised. Despite the rarity of phaeochromocytoma, clinicians should exercise caution in the use of metoclopramide among hypertensives and those with labile blood pressures, given the potentially life-threatening crisis it can readily evoke in those with this tumour. We report a series of three patients with phaeochromocytoma who developed acute crises from metoclopramide.

Adrenal Gland Neoplasms↗

Clinical utility of selective intra-arterial calcium-stimulated hepatic venous sampling in regionalisation of insulinomas--the Singapore experience.

INTRODUCTION: To evaluate the efficacy and safety of selective intra-arterial calcium-stimulated hepatic venous sampling (ASVS) as a preoperative regionalisation modality for insulinomas. DESIGN AND METHODS: Four patients with biochemically-proven endogenous hyperinsulinism and negative spiral computed tomographic (CT) pancreas were subjected to ASVS between October 1999 to May 2001. Results obtained from ASVS were compared with localisation studies using either magnetic resonance imaging (MRI) or endoscopic ultrasonography (EUS); and these were confirmed surgically whenever possible. RESULTS: ASVS led to a definitive regionalisation in all 4 patients evaluated; the predicted location of the insulinoma matched the findings intraoperatively in all 3 patients who were operated upon. These were all proven to be insulinoma histologically. However, 1 patient showed a positive ASVS result in samples obtained from the left hepatic vein only. In the patient who was unable to undergo surgical resection due to other co-morbid factors, his ASVS findings were corroborated by localisation obtained from the MRI study. Conversely, EUS was found to give an incorrect localisation of insulinoma in 1 patient. Adverse effects were encountered in 3 patients (2 with mild hypotension and 1 with transient atrial fibrillation); however, premature termination of the procedure was not necessary in any of the patients. CONCLUSION: ASVS is accurate and reliable for regionalisation of insulinoma, especially in patients who do not have an obvious, unequivocal tumour using high quality current-generation MRI scans.

Adult↗

Current therapeutic strategies for type 2 diabetes mellitus.

Type 2 diabetes mellitus is now regarded a worldwide epidemic with diabetes-related complications exacting a heavy toll on those with poor metabolic control. Although there is no cure currently, the therapeutic armamentarium has expanded over the last few years to five classes of oral agents--sulfonylureas, biguanides, meglitinides, thiazolidinediones and alpha-glucosidase inhibitors. Sulfonylureas continue to be the mainstay oral hypoglycaemic agents for type 2 diabetics because they are potent insulin secretagogues and cost-effective. Metformin exerts its main effect by reducing hepatic glucose output and is proven to particularly benefit obese type 2 diabetics. Meglitinides are rapid-acting insulin secretagogues targeting a postprandial hyperglycaemia and this class of drug is useful for those who are at risk of hypoglycaemia with longer-acting sulfonylurea drugs. Thiazolidinediones constitute a new class of insulin sensitizers that work predominantly in improving glucose uptake by the adipose tissues and skeletal muscles. Alpha-glucosidase inhibitors delay the digestion and absorption of polysaccharides, thus attenuating postprandial hyperglycaemia. This review article briefly examines the nature of these oral agents, including the role of combination therapy and insulin where clinically indicated.

Administration, Oral↗

Identification of rat mammary tumor-1 gene (RMT-1), which is highly expressed in rat mammary tumors.

Full-term pregnancy early in life results in a permanent reduction in lifetime breast cancer risk in women. Parous rats and mice are also refractory to chemical carcinogenesis. Therefore, investigation of the differences between mammary glands from virgin and parous rats would provide valuable information regarding the protective effects of early full-term pregnancy. In this report, we examined the gene expression patterns in mammary glands from virgin and parous Lewis rats. Using differential display technology, a novel 4.2 kb cDNA, designated rat mammary tumor-1 (RMT-1) was isolated. Northern blot analysis of RMT-1 showed that RMT-1 expression was higher in the pre-pubertal and pubertal stages during rat mammary gland development while it was down-regulated in mammary glands from mature virgin and parous rats. RMT-1 expression was highest in rat mammary cancers compared with either the mammary glands of virgin or parous rats. At the Northern blot sensitivity level, RMT-1 expression was found only in the mammary gland. Northern blot analysis also showed that the expression of this gene was found in 74% of N-methyl-nitrosourea (MNU)-induced mammary cancers while it was not found in MNU-induced cancers from other organs. The examination of the RMT-1 gene structure revealed that it consists of five exons spanning 5.9 kb. Using fluorescence in situ hybridization, the gene was localized on rat chromosome 1 band q 43-51. The present data show that there is a correlation between high RMT-1 expression and rat mammary carcinogenesis or decreased RMT-1 expression and parity associated refractoriness to chemically induced mammary carcinogenesis. However, whether or not RMT-1 gene has a functional role in these processes remains to be investigated.

Amino Acid Sequence↗

Contribution of axial dispersion to band spreading in perfusion chromatography.

A new interpretation of the band spreading data in perfusion chromatography is proposed by investigating the relative importance of axial dispersion in perfusive beds. Elution chromatography of proteins (bovine serum albumin and lysozyme) under non-retained conditions on two kinds of reversed-phase perfusive supports (POROS R1/H and POROS R2/H), which have different pore structures, were carried out to obtain the axial dispersion data. The Knox equation and some empirical correlations for dispersion coefficients in porous media were applied to correlate the experimental data. The influences of particle properties, solute molecular sizes and flow velocity on the dispersion coefficient were elucidated. Axial dispersion was recognised to be the main contributor to peak broadening in perfusion chromatography. The dependence of the height equivalent to a theoretical plate on flow-rate was found to be the result of the velocity dependence of the axial dispersion. The dispersion coefficient in a perfusive column can be well represented both by a power-law relationship and a correlation derived based on stochastic theory. Pursuant to these, it was found that pore size distribution of the perfusive particles and solute molecular size are important parameters, which influenced the dispersion results significantly.

Chromatography↗

Biotransformation kinetics of Pseudomonas putida for cometabolism of phenol and 4-chlorophenol in the presence of sodium glutamate.

A kinetic model to describe the degradation of phenol and cometabolic transformation of 4-chlorophenol (4-cp) in the presence of sodium glutamate (SG) has been developed and validated experimentally. The integrated model accounts for cell growth, toxicity of 4-cp, cross-inhibitions among the three substrates, and the different roles of the specific growth substrate (phenol) and the conventional carbon source (SG) in the cometabolism of 4-cp. In this ternary substrate system, the overall phenol degradation and 4-cp transformation rates are greatly enhanced by the addition of SG since SG is able to attenuate the toxicity of 4-cp and therefore increase the cell growth rate. Model analysis indicates that the maximum specific degradation rate of phenol (0.819 mg (mg.h)(-1)) is lowered by SG by up to 46% whereas the specific transformation rate of 4-cp is not directly affected by the presence of SG. The competitive inhibition coefficient of 4-cp to phenol degradation (Ki,cp) and that of phenol to 4-cp transformation (Ki,ph) were determined to be 6.49 mg l(-1) and 0.193 mg l(-1), respectively, indicating that phenol imposes much larger competitive inhibition to 4-cp transformation than the converse. The model developed can simultaneously predict phenol degradation and 4-cp transformation, and is useful for dealing with cometabolism involving multiple substrates.

Algorithms↗

46, XY female--a case report.

INTRODUCTION: We examine a presumptive case of complete androgen insensitivity syndrome (CAIS) with certain unusual features. CLINICAL PICTURE: A woman with early onset osteoporosis gave a history of primary amenorrhoea and surgery for intraabdominal gonads. She subsequently defaulted follow-up and hormone replacement therapy. Endocrinological evaluation revealed hypergonadotrophic hypogonadism associated with a 46,XY karyotype. TREATMENT: Therapy included reinforcement of the female phenotype and oestrogen replacement. OUTCOME: There was gradual development of her secondary sexual characteristics and improvement in her bone mineral density. CONCLUSION: Patients with CAIS need proper counselling and education according to their psychosexual make-up and sociocultural factors. The importance of long-term oestrogen replacement in a young subject post-gonadectomy cannot be overemphasized as illustrated in our case.

Adult↗

Gynaecomastia and the herbal tonic "Dong Quai".

We present a case of a man who developed gynaecomastia after ingestion of "Dong Quai" pills. "Dong Quai" is the Chinese name for the herb Angelica polymorpha var. sinensis which is widely used as a panacea for gynaecological problems, and it is also proclaimed as an invigorating tonic for both women and men. The pharmacological effects of "Dong Quai" are likely related to the phytoestrogen that it contains. This report highlights the potential adverse effects associated with its consumption in the male, especially for the processed "Dong Quai" pills which may contain significantly higher levels of phytoestrogen than its original herbal product.

Adult↗

Thyrotrophin (TSH)-secreting pituitary macroadenoma with cavernous sinus invasion.

Thyrotrophin (TSH)-secreting pituitary adenomas, although rare, should be recognised as a possible cause of normal or elevated serum TSH in the presence of elevated serum free thyroid hormone levels. Clinical hyperthyroidism may be mild or absent. Early recognition provides the best chance for surgical cure. We report a patient with a TSH-secreting pituitary tumour with cavernous sinus invasion. This case illustrates that multiple modalities of treatment are often necessary and complementary in achieving control of tumour growth and hormonal hypersecretion when these tumours are diagnosed late.

Adenoma↗

Growth kinetics of Pseudomonas putida in cometabolism of phenol and 4-chlorophenol in the presence of a conventional carbon source.

Growth kinetics of Pseudomonas putida (ATCC 49451) in cometabolism of phenol and 4-chlorophenol (4-cp) in the presence of sodium glutamate (SG) were studied. In the ternary substrate mixture, phenol and SG are growth substrates while 4-cp is a nongrowth substrate. Cell growth on phenol was found to follow Andrews kinetics and cells displayed substrate inhibition pattern on sodium glutamate in the range of 0-4 g L(-1) as well. A cell growth model for the ternary substrate system was established based on a simplified cell growth mechanism and subsequently modified by experimental results. Model analysis over a wide range of substrate concentrations shows that the inhibition of SG is much larger than phenol at low phenol concentrations (</=200 mg L(-1)) while phenol exerts dominant inhibition on cell growth at higher phenol concentrations (>/=600 mg L(-1)). The nongrowth substrate, 4-cp, inhibits cell growth mainly through inactivation of cells (cell decay) and competitive inhibition to cell growth on phenol. In the absence of SG, 4-cp retards cell growth severely and cells cannot grow at 250 mg L(-1) 4-cp. Addition of sodium glutamate, however, greatly attenuates the toxicity of 4-cp and supports cell growth at 4-cp concentration higher than 250 mg L(-1). By using the proposed cell growth model, we were able to optimize the amount of SG needed to enhance cell growth rate and validate model predictions against experimental data.

Biotechnology↗

Death from thyroid cancer of follicular cell origin.

BACKGROUND: Although patients with differentiated thyroid cancer (DTC) of follicular cell origin usually have an excellent prognosis, some patients die from progressive tumor. Numerous postoperative criteria have been used to predict prognosis in patients with DTC. The purpose of this investigation was to determine whether the TNM and metastases, age, completeness of resection, invasion, size (MACIS) classifications predicted survival time and why patients died from DTC. The extent of initial treatment and causes of death were also evaluated in these patients who died from thyroid cancer. STUDY DESIGN: Between 1965 and 1995, 102 of 1,224 patients with DTC treated at the University of California at San Francisco (UCSF) and UCSF/Mount Zion Medical Centers died from DTC. Risk factors including age at diagnosis, gender, histologic characteristics, TNM and MACIS classifications, the intervals among initial treatment, recurrence, and death, and the initial and subsequent treatments were documented in these 102 patients. RESULTS: Among the 102 patients who died of DTC 50% were men and 50% were women. The mean age of patients with DTC at diagnosis was 58 years at recurrence, 62 and 65 years at death. Thirty percent of these patients initially had unilateral thyroid operations and 70% had a bilateral operation. Tumors at presentation ranged from 0.6 to 13.0 cm (mean 4.4 cm); 46% of patients presented with late-stage tumors (TNM stage III, IV; MACIS score > 8). At presentation 46% of the patients had locally recurrent disease or regional metastases and 18% had distant metastases. Patients with persistent disease had a significantly shorter survival time than those with recurrent disease (p < 0.001). Both TNM and MACIS classifications were good predictors of survival time. Reoperations were performed in 51% of papillary, 26% of follicular, and 67% of Hürthle cell thyroid cancer patients. Fifty percent of patients with papillary thyroid cancer, 50% of patients with Hürthle cell thyroid cancer, and 11% of patients with follicular cell thyroid cancer died of locally advanced disease. CONCLUSIONS: As expected, patients with local or regional recurrence and those with TNM stage I or MACIS score < 6 survived longer than patients with distant metastasis and TNM stage III or IV, MACIS score > 6, but some patients thought to be at low risk (TNM stage I; MACIS < 6) also died from thyroid cancer.

Adenocarcinoma, Follicular↗

Amiodarone-induced thyroid disorders: a clinical review.

Although amiodarone is regarded as a highly effective anti-arrhythmic agent, its use may lead to alterations in thyroid gland function and/or thyroid hormone metabolism, partly because of its rich iodine content. Patients treated with amiodarone may manifest altered thyroid hormone profile without thyroid dysfunction, or they may present with clinically significant amiodarone-induced hypothyroidism or amiodarone-induced thyrotoxicosis. The former results from the inability of the thyroid to escape from the Wolff-Chaikoff effect. It prevails in areas with high dietary iodine intake, and it is readily managed by discontinuation of amiodarone or thyroid hormone replacement. Amiodarone-induced thyrotoxicosis occurs more frequently in areas with low iodine intake; it may arise from iodine-induced excessive thyroid hormone synthesis (type I) or destructive thyroiditis with release of preformed hormones (type II). Type I should be treated with thionamides alone or in combination with potassium perchlorate, whereas type II benefits from treatment with glucocorticoids. Surgery may be a feasible option for patients who require long-term amiodarone treatment.

Amiodarone↗

Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore.

Recent studies using the ratio of plasma aldosterone concentration (PAC) to PRA as the screening test for primary aldosteronism in hypertensive populations suggested that the prevalence may be as high as 5-15%, with well over half of the subjects having normal serum potassium concentrations. Despite an increasing clinical awareness of this entity, many clinicians are reluctant to consider routine screening for primary aldosteronism in essential hypertensive patients because there are few community-based prevalence studies of primary aldosteronism in different populations. Furthermore, genetic and environmental differences may affect the prevalence and presentation of primary aldosteronism in distinct populations. This study was designed to determine the prevalence of primary aldosteronism in the predominantly Chinese population in Singapore. Three hundred and fifty unselected adult hypertensive patients attending two primary care clinics had random ambulatory measurements for PAC (nanograms per dL) and PRA (nanograms per mL/h). Serum urea, creatinine, and electrolyte measurements were obtained simultaneously. Subjects with renal insufficiency (serum creatinine, >140 micromol/L) and those treated with glucocorticoids or spironolactone were excluded. Screening was considered positive if the PAC: PRA ratio was more than 20 and the PAC was more than 15 ng/dL (>416 pmol/L). Primary aldosteronism was confirmed with the determination of PAC after 2 L saline administered iv over 4 h. Adrenal computed tomographic (CT) scans were performed in biochemically confirmed cases of primary aldosteronism. Further localization with adrenal vein sampling was carried out in selected patients with equivocal findings on adrenal CT scan. Sixty-three (18%) of the 350 hypertensive patients (215 women and 135 men; age range, 23-75 yr) were screened positive for primary aldosteronism. Only 13 of these 63 subjects (21%) were hypokalemic (serum potassium, <3.5 mmol/L). Confirmatory studies were carried out in 56 (89%) of the subjects with a positive PAC:PRA ratio. Using a PAC above 10 ng/dL (>277 pmol/L) after saline infusion as the diagnostic cut-off, 16 of the 56 patients had biochemically confirmed primary aldosteronism. Hypokalemia was found in 6 of the 16 patients (37.5%) with primary aldosteronism. Subtype evaluation with adrenal CT scan and adrenal vein sampling indicated that half of the patients with primary aldosteronism may have had potentially curable unilateral adrenal adenoma. Our data suggest that primary aldosteronism occurs in at least 5% of the adult Asian hypertensive population, and approximately half of these individuals may have potentially curable, unilateral, aldosterone-producing adrenal adenoma. Our findings also confirm the poor predictive value of hypokalemia in both the diagnosis and the exclusion of primary aldosteronism.

Adult↗

Hypoglycaemia from islet cell hyperplasia and nesidioblastosis in a patient with type 2 diabetes mellitus--a case report.

INTRODUCTION: We report the first case of hypoglycaemia from beta cell hyperplasia with nesidioblastosis in an Asian adult with pre-existing type 2 diabetes. CLINICAL PICTURE: A 57-year-old Chinese woman presented with hyperinsulinaemic hypoglycaemia despite discontinuation of oral hypoglycaemic agents 4 months after diagnosis of type 2 diabetes. Preoperative portal venous sampling suggested regionalisation to the neck of the pancreas. Intraoperative ultrasound and palpation of the fully mobilised pancreas were non-localising. TREATMENT: A subtotal 85% pancreatectomy was performed with success. OUTCOME: Histology showed no evidence of tumour, but revealed islet hyperplasia and nesidioblastosis. Her diabetes was subsequently well controlled on metformin therapy. CONCLUSION: Endogenous hyperinsulinism from beta cell hyperplasia with nesidioblastosis may rarely occur in type 2 diabetics. However, this remains a diagnosis of exclusion that is confirmed only on surgical pathology. In affected individuals, preoperative portal venous sampling may be falsely localising, especially if selective sampling of the smaller peri-pancreatic veins is omitted. Definite treatment involves pancreatectomy, although the extent of surgical resection is not well established.

Diabetes Mellitus, Type 2↗