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Biomedical subjects

Y Y Tan

Publications and source records attributed to Y Y Tan.

At least 19 recordsLinked to original sources

Selective modified radical neck dissection for papillary thyroid cancer-is level I, II and V dissection always necessary?

BACKGROUND: There is ongoing controversy as to the indications for and extent of lateral cervical lymphadenectomy for patients with papillary thyroid cancer (PTC). While most now agree that prophylactic lymph node dissections (LND) play no role, at the University of California, San Francisco (UCSF) we limit LND selectively on a level by level basis, and resect only the levels thought to harbor disease or to be at increased risk of metastases. This initial 'selective LND' usually includes levels III and IV (due to the well-documented increased likelihood of metastases to these levels) and levels I, II, and V are included when there is clinical or radiological evidence of disease or increased risk of it. METHODS: A retrospective review of the clinical charts and hospital records of 106 consecutive patients who had metastatic PTC and who underwent at least one lateral cervical LND at UCSF between January 1995 and December 2003 was carried out. Data were collected to assess which patients had levels I, II, and/or V included in their initial ipsilateral and/or contralateral LND and to determine the recurrence rates at these levels if they had previously been excised compared with if they had not. Chi-squared and Fisher exact tests were utilized for statistical comparison, where appropriate. RESULTS: A total of 140 initial lateral LND were performed: 104 ipsilateral and 36 contralateral. In these initial LND, 3.9%, 72.5%, and 18.6% of patients had levels I, II, and V resected on the ipsilateral side, and 2.9%, 60.0%, and 37.1% of patients had levels I, II, and V resected on the contralateral side. Recurrence at levels I and V was uncommon in all patient populations. Recurrence at level II was 19% ipsilaterally and 10% contralaterally when the level was previously resected and 21% ipsilaterally and 14% contralaterally when the level was not previously resected. There was no statistically significant difference in recurrence at level II when the level had previously been resected compared with when it had not. CONCLUSIONS: If utilized in the appropriate patient population, a selective approach to lateral cervical LND for PTC can be a successful alternative to the routine modified radical LND. Levels I and V do not require resection unless there is clinical or radiological evidence of disease. Guidelines for which patients may be considered for this less aggressive approach to level II nodal metastases are suggested.

Adenocarcinoma, Papillary↗

Predictors of axillary lymph node metastases in women with early breast cancer in Singapore.

INTRODUCTION: The presence of axillary lymph node metastases is an important prognostic factor in breast cancer. Sentinel lymph node biopsy (SLNB) is an emerging method for the staging of the axilla. It is hoped that with SLNB, the morbidity from axillary lymph node dissection (ALND) can be avoided without compromising the staging and management of early breast cancer. However, only patients found to be SLNB negative benefit from this procedure, as those with positive SLNB may still require ALND. Our objective is to study the various clinico-pathological factors to find predictive factors for axillary lymph node involvement in early breast cancer. It is hoped that with these factors, we will be better able to identify groups of patients most likely to benefit from SLNB. METHODS: A retrospective study of 380 early breast cancer cases (stage T1 and T2, N0, N1, M0) in women treated in the Department of General Surgery, Tan Tock Seng Hospital, between January 1999 and August 2002, was conducted. Incidence of nodal metastases was correlated with clinico-pathological factors, and analysed by univariate and multivariate analyses. RESULTS: Approximately 35 percent of the 380 cases of early breast cancer had nodal metastases. Multivariate analyses revealed four independent predictors of node positivity: tumour size (p-value equals 0.0001), presence of lymphovascular invasion (p-value is less than 0.0001), tumours with histology other than invasive ductal or lobular carcinoma (p-value equals 0.04), and presence of progesterone receptors (p-value equals 0.05). CONCLUSION: We have found independent preoperative predictive factors in our local population for the presence of nodal metastases. This information can aid patient selection for SLNB and improve patient counselling.

Adult↗

Influences of gender and region on responses to 5-HT in the rat small intestine.

The aim of this study was to obtain more information regarding the 'atypical' 5-HT7 receptor of the rat jejunum. 5-HT7-induced contractions of the jejunum were elicited by 5-HT in the presence of ondansetron. Maximal responses were slightly larger in tissues from male compared to female rats of comparable age, with Emax values of 97.2 +/- 3.3 and 84.25 +/- 4.3% respectively compared to acetylcholine as an internal standard. However, the pEC50 values for 5-HT were not significantly different. The mRNA expression levels of the 5-HT7 receptor were similar in whole jejunum and longitudinal muscle tissues taken from males and females. It was also shown that the maximal response of the jejunum from male rats was larger than the responses from mid intestine and ileum. However, in female tissues, the Emax of the mid intestine was significantly larger than the ileum, but not different from the jejunum. The results provide further insights into the 'atypical' 5-HT7 receptor of the rat jejunum and are also useful in optimising the preparation for further studies.

Acetylcholine↗

In planta regulation of extension of an endophytic fungus and maintenance of high metabolic rates in its mycelium in the absence of apical extension.

The fungus Neotyphodium lolii is an endophytic symbiont. It grows in the intercellular spaces of the perennial ryegrass Lolium perenne, producing secondary metabolites which enhance the fitness of the association over that of uninfected L. perenne. We report that the average number of hyphal strands in a given section of a leaf remains constant during the life of a leaf, indicating synchrony of leaf and hyphal extension, including cessation of hyphal extension when leaf extension ceases. We used a constitutively expressed reporter gene as an indicator of the mycelium's metabolic activity during and after hyphal extension. Reporter gene activity decreased when the mycelium stopped extending in liquid culture but not in planta. This indicates that in planta endophyte hyphae remain metabolically highly active when extension has ceased and throughout the life of the leaf they are colonizing. The behavior of the fungus in planta indicates the existence of signaling pathways which (i) synchronize the extension of leaf and hypha by regulating hyphal extension, (ii) suppress hyphal branching, and (iii) stop apical extension of fungal hyphae, without reducing the mycelium's metabolic activity. These signals may be crucial for the symbiosis, by allowing the endophyte to switch the focus of its metabolic activity from extension to the production of secondary metabolites.

Ascomycota↗

Melioidosis splenic abscess--an unusual presentation as osteomyelitis of rib.

INTRODUCTION: We report an unusual case of splenic melioidosis abscess presenting as osteomyelitis. CLINICAL PICTURE: A 74-year-old nondiabetic gentleman presents with a non-healing left chest wall abscess from osteomyelitis. TREATMENT: He underwent rib resection and the infection was found to involve the underlying pleura, lung, adjacent stomach, liver and diaphragm with a splenic abscess. Splenectomy was performed. Histology showed suppurative granulomas and cultures grew Burkholderia pseudomallei. OUTCOME: The patient recovered well with antibiotics. CONCLUSION: Melioidosis should not be forgotten as a cause of chronic suppurative infections in our endemic population.

Abscess↗

Novel strategy for the synthesis of template-assembled analogues of rat relaxin.

The 'template-assembled synthetic protein' (TASP) concept provides a simple and elegant approach for the preparation of analogues that retain key structural elements. We have synthesized TASP molecules containing the putative active site of relaxin, a peptide that has similar structural features to insulin but a markedly different biological role. Two types of chemoselective thiol ligation strategies (thioether and thiazolidine) were used and compared. The synthetic pendant peptides contain an essential region for bioactivity that is located in the alpha-helical region of the relaxin B-chain. Depending on whether the thioether or the thiazolidine chemistry was used to attach the peptides to the template, the reacting amino acid was placed either at the C-terminus or N-terminus, respectively, thus allowing the choice of orientation relative to the carrier molecule. The template molecule consists of a decapeptide with two proline-glycine turns and four evenly spaced lysine residues that were functionalized with the appropriate chemical moiety. This allowed reaction with the appropriately derivatized peptides in solution. To improve the template ligation step using the thioether approach, a pendant peptide C-terminal cysteamine residue was used to reduce potential steric hindrance during conjugation. The design of the peptides as well as the synthetic strategy resulted in the acquisition of mimetics showing weak non-competitive and weak competitive antagonist properties.

Animals↗

Solid-phase synthesis of ovine Leydig cell insulin-like peptide--a putative ovine relaxin?

The primary structure of ovine Leydig cell insulin-like peptide (Ley I-L) was recently deduced from the corresponding cDNA sequence. It consists of two peptide chains and three disulphide bonds in an arrangement similar to both relaxin and insulin. As in relaxin B-chain, an Arg-X-X-X-Arg sequence exists within the Ley I-L B-chain although it is located four residues towards the C-terminus from the corresponding position within relaxin. This sequence of amino acids is known to be essential for relaxin biological activity and its presence in Ley I-L suggested that the peptide might possess a relaxin-like function. Ovine Ley I-L was assembled by Fmoc-solid-phase synthesis of the separate chains followed by their combination in solution at high pH. The purity and identity of the chain-combined peptide was confirmed by chemical characterization including mass spectrometry. At physiological concentrations, the peptide was shown not to possess relaxin-like activity in the rat isolated atrial chronotropic and inotropic assay. This strongly suggests that Ley I-L is not a relaxin in the sheep. In order to explore further a possible structural relationship between Ley I-L and relaxin, we prepared a synthetic analogue of ovine Ley I-L containing a single replacement of B-chain residue 12, His, with Arg. This was found to possess significant relaxin-like chronotropic and inotropic activity demonstrating that the tertiary structure of Ley I-L is similar to that of relaxin and highlighting the key requirement for the five-residue sequence, Arg-X-X-X-Arg, to be present in position B12-16 for characteristic relaxin activity.

Amino Acid Sequence↗

Quantitative autoradiographic studies of relaxin binding in rat atria, uterus and cerebral cortex: characterization and effects of oestrogen treatment.

The binding characteristics of the relaxin receptor in rat atria, uterus and cortex were studied using a [33P]-labelled human gene 2 relaxin (B33) and quantitative receptor autoradiography. The binding kinetics of [33P]-human gene 2 relaxin (B33) were investigated in slide-mounted rat atrial sections. The binding achieved equilibrium after 60 min incubation at room temperature (23+/-1 degrees C) and dissociated slowly. The association and dissociation rate constants were 4.31+/-0.34x10(8) M(-1) x min(-1) and 1.55+/-0.38x10(-3) min(-1) respectively. Thus, the kinetic dissociation constant was 3.46+/-0.59 pM. Binding was saturable to a single population of non-interacting sites throughout atria, in uterine myometrium and the 5th layer of cerebral cortex. The binding affinities (pK(D)) of [33P]-human gene 2 relaxin (B33) were 8.92+/-0.09 in atrial myocardium and 8.79+/-0.04 in cerebral cortex of male rats, and 8.79+/-0.10 in uterine myometrium. Receptor densities in the cerebral cortex and atria were higher than in uterine myometrium, indicating that relaxin also has important roles in non-reproductive tissues. In male rats, treatment with 17beta-oestradiol (20 microg in 0.1 ml sesame oil s.c., 18-24 h) significantly decreased the density of relaxin receptors in atria and cerebral cortex. Identical treatment in female rats had no significant effect in atria and cerebral cortex, but it significantly increased the density of relaxin receptors in uterine myometrium. Relaxin binding was competitively displaced by porcine and rat native relaxins. Porcine native relaxin binds to the relaxin receptor in male rat atria (8.90+/-0.02), and cerebral cortex (8.90+/-0.03) and uterine myometrium (8.89+/-0.03) with affinities not significantly different from human gene 2 (B33) relaxin. Nevertheless, rat relaxin binds to the receptors with affinities (8.35+/-0.09 in atria, 8.22+/-0.07 in cerebral cortex and 8.48+/-0.06 in uterine myometrium) significantly less than human gene 2 (B33) and porcine relaxins. Quantitative receptor autoradiography is the method of choice for measurement of affinities and densities of relaxin receptor in atria, uterine myometrium and cerebral cortex. High densities were found in all these tissues. 17beta-oestradiol treatment produced complex effects where it increased the densities of relaxin receptors in uterus but decreased those in atria and cerebral cortex of the male rats, and had no effect on the atria and cerebral cortex of the female rats.

Animals↗

A case report on aggressive fibromatosis with bone involvement.

Aggressive fibromatosis is a locally infiltrative fibroblastic tumour that arises from fascial planes of soft tissue but does not metastasize. It is known to invade muscle, subcutaneous tissue and neurovascular structures. However, bone involvement is very rare and there has been few reports of bone involvement. We present a case of a young man with aggressive fibromatosis of the right lower leg with fibula involvement.

Adult↗

Comparison of relaxin receptors in rat isolated atria and uterus by use of synthetic and native relaxin analogues.

1. The receptors for relaxin in the rat atria and uterus were investigated and compared by use of a series of synthetic and native relaxin analogues. The assays used were the positive chronotropic and inotropic effects in rat spontaneously beating, isolated right atrium and electrically driven left atrium and the relaxation of K+ precontracted uterine smooth muscle. 2. Relaxin analogues with an intact A- and B-chain were active in producing powerful chronotropic and inotropic effects in the rat isolated atria at nanomolar concentrations. Single-chain analogues and structural homologues of relaxin such as human insulin and sheep insulin-like growth factor I had no agonist action and did not antagonize the effect of the B29 form of human gene 2 relaxin. 3. Shortening the B-chain carboxyl terminal of human gene 1 (B2-29) relaxin to B2-26 reduced the activity of the peptide and removal of another 2 amino acid residues (B2-24) abolished the activity. This suggests that the B-chain length may be important for determination of the activity of relaxin. More detailed studies are needed to determine the effect of progressive amino acid removal on the structure and the bioactivity of relaxin. 4. Porcine prorelaxin was as active as porcine relaxin on a molar basis, suggesting that the presence of the intact C-peptide did not affect the binding of the prorelaxin to the receptor to produce functional responses. 5. Relaxin caused relaxation of uterine longitudinal and circular smooth muscle precontracted with 40 mM K+. The pEC50 values for human gene 2 and porcine relaxins were lower than those in the atrial assay, but rat relaxin had similar pEC50 values in both atrial and uterine assays. Rat relaxin was significantly less potent than either human gene 2 or porcine relaxin in the atrial assay, but in the uterine assay they were equipotent. The results suggest that the relaxin receptor or the signalling pathway in rat atria may differ from that in the uterus.

Animals↗

Verrucous haemangioma--a case report.

Verrucous haemangioma is an uncommon skin lesion which increases in size and also evolves in appearance with time. Early diagnosis is important so that surgical treatment can be instituted early for better cosmetic results. Its similarities and differences to angiokeratoma circumscriptum are also highlighted, and the importance of distinguishing the two in terms of management is discussed.

Abdomen↗

Impaired glucose tolerance in pregnancy--is it of consequence?

This study was done to determine if impaired glucose tolerance in pregnancy was associated with increased maternal and neonatal morbidity and if so, whether the increased morbidity was due to the confounding factors of increased maternal age and maternal obesity. It was a retrospective analysis to compare 944 women with impaired glucose tolerance (IGT) in pregnancy with 10,065 women without abnormal glucose tolerance. The incidence of impaired glucose tolerance in pregnancy was 8.6% in this study. Even when maternal age and obesity were excluded, the IGT group had significantly higher risks of labour induction (relative risk, RR, 1.15); Caesarean section (RR: overall 1.43, elective 1.72, emergency 1.31); Caesarean section for dystocia/no progress (RR 1.60); macrosomia (RR 1.69, 1.76, 1.61 for birth-weight > = 97th, 95th, 90th percentiles respectively) and shoulder dystocia (RR 2.84) when compared to the nondiabetics (NDM). The risks of hypertensive disease (RR 1.22) and Caesarean section for fetal distress/thick meconium-stained liquor (RR 1.53) were also higher in the IGT group but these increases were not statistically significant when maternal age and obesity were excluded. There was no significant difference in the rates of low Apgar scores at 1 and 5 minutes between the 2 groups.

Cesarean Section↗

Is postnatal oral glucose tolerance testing necessary in all women with gestational diabetes.

Currently, women with gestational diabetes mellitus have a repeat oral glucose tolerance test 6 weeks after delivery to identify those with persistent glucose intolerance. In this study, 298 women with gestational diabetes had a postnatal oral glucose tolerance test and of these, 23.2% had persistent glucose intolerance after delivery. The aim of this study was to determine if the antenatal oral glucose tolerance test results could be used to predict which patients would have persistent glucose intolerance after delivery. If only those with severely abnormal antenatal results had persistent disease, then those with only mildly abnormal antenatal results could be spared the postnatal oral glucose tolerance test. Using receiver operator characteristic curves, this study showed that the antenatal oral glucose tolerance test results could not be used to predict reliably which patients would continue to have abnormal glucose tolerance postnatally. Hence, postnatal oral glucose tolerance testing of all patients with gestational diabetes is still necessary as the detection of persistent glucose intolerance is important for the control of the diabetic condition so as to minimise long-term complications.

Adult↗

Uterine cancer--the KK Hospital experience.

Kandang Kerbau Hospital saw 165 new cases of uterine cancers over the 4-year period from 1991 to 1994. The median age of presentation was 54.1 years and 10.9% of these cases occurred in those aged less than 40 years, unlike the corresponding figures of 61 years and less than 5%, respectively, which are often quoted for endometrial cancers in standard textbooks. Endometrioid adenocarcinoma was the commonest type of uterine cancer seen in our population (75.2%) as in other series. However, we had fewer cases of adenoacanthoma (1.4%) and adenosquamous carcinoma (1.4%) but more cases of uterine sarcoma (11.5%) than is usually reported. 6.7% of our patients had papillary serous adenocarcinoma and 3.0% had clear cell carcinoma. These 2 sub-types are associated with poorer prognosis and there is a need to increase awareness of their existence in our local population as their management differs from that for the usual endometrioid adenocarcinoma. We had fewer patients with stage I disease (53.3%) but more patients with stage III disease (22.4%). This is most likely due to the use of surgico-pathological staging currently as opposed to the clinical staging used previously which led to the under-staging of a proportion of patients.

Adenocarcinoma, Clear Cell↗

beta-Adrenoceptor regulation in rat heart, lung and skin after chronic treatment with (--)-tertatolol or (--)-propranolol.

1. The effect of long-term treatment with the beta-adrenoceptor antagonists (--)-tertatolol and (--)-propranolol was studied. Sprague-Dawley rats were treated with either (--)-tertatolol (50 micrograms kg-1 hr-1), (--)-propranolol (250 micrograms kg-1 hr-1) or vehicle (1 mM HCl) for 14 days with osmotic minipumps implanted subcutaneously. 2. The mean daily systolic blood pressure and heart rate of rats treated with either (--)-tertatolol (108 +/- 1 mmHg/330 +/- 3 bpm) or (--)-propranolol (103 +/- 1 mmHg/330 +/- 2 bpm) were lower than in the control (126 +/- 1 mmHg/405 +/- 3 bpm, P < 0.001, n = 8-10) indicating the effectiveness of drug delivery. 3. Autoradiographic studies in areas of heart, lung and skin showed that beta-adrenoceptor populations were not significantly affected by the drug treatment (all regions P > 0.05). Nevertheless, the receptor population in the homogenates of (--)-tertatolol treated lung were halved (194 +/- 28 fmol mg protein-1 compared with a control value of 388 +/- 54 fmol mg protein-1, P < 0.01, n = 6). 4. In the presence of CGP 20712A, the left atrial inotropic and right atrial chronotropic responsiveness to (--)-isoprenaline were hypersensitive in both (--)-tertatolol and (--)-propranolol-treated groups (P < 0.005, ANCOVA). 5. (--)-Propranolol treated left ventricular free wall had lower basal [3H]-forskolin binding to adenylate cyclase (14.45 +/- 1.20 fmol mg protein-1 compared with a control value of 18.91 +/- 0.78 fmol mg protein-1, P = 0.01, n = 6). (--)-Tertatolol treatment had no effect on the basal binding. In the presence of the G-protein activators NaF and Gpp(NH)p, the enhancement of [3H]-forskolin binding did not differ between control and the drug treated groups. 6. Chronic (--)-tertatolol or (--)-propranolol treatment therefore did not produce an increase in receptors in heart, lung or skin but the beta-adrenoceptor-mediated responses were enhanced. In addition, [3H]-forskolin binding did not increase suggesting that the hypersensitivity was not due to changes in the number of receptors or adenylate cyclase. Hypersensitivity following beta-adrenoreceptor antagonist administration may therefore involve enhanced coupling of receptors to G-proteins.

Adrenergic beta-Agonists↗

Second trimester colour Doppler imaging of the uterine artery: reproducibility of the resistance index.

Second trimester assessment of uterine blood flow has been advocated as a predictor of subsequent adverse perinatal outcome. The reproducibility of uterine artery resistance index, as assessed using colour Doppler imaging, was investigated. Two observers, both of whom were experienced in colour Doppler assessment of uterine artery flow velocity waveforms, performed the measurements. One-way analysis of variance was used to evaluate intraobserver variability and the limits of agreement method was used to determine the 95% prediction interval for interobserver differences. The intraobserver standard deviation was small for both observers. The limits of agreement for interobserver differences were wide (-0.24, 0.16), similar in magnitude to those reported by other workers who assessed the uterine vessel using continuous wave Doppler. The poor reproducibility of the resistance index suggests that second trimester Doppler assessment of uterine artery flow velocity waveforms may be better described using other semiquantitative methods such as the presence or absence of a diastolic notch.

Female↗

Using glucose tolerance test results to predict insulin requirement in women with gestational diabetes.

This study was done to test the clinical impression that the result of the oral glucose tolerance test could be used to predict which patients with gestational diabetes did not need insulin therapy. If this was true, a full blood sugar profile assessment could be avoided in many of these women. The second analysis was to test the clinical impression that the fasting glucose level was the best predictor of insulin requirement in women with gestational diabetes. The results of the study showed that none of the 3 readings of the oral glucose tolerance test could be used to predict reliably which patients did not need insulin therapy. Hence, blood sugar profile assessment of all patients with gestational diabetes is still necessary. The receiver-operator characteristic curves also showed that the 2-hour postload glucose level during the 75 g load glucose tolerance test was a better predictor of insulin requirement than the fasting glucose level.

Blood Glucose↗