Biomedical subjects
Publications and source records attributed to S Chua.
Familial aggregation of diabetic nephropathy has suggested an important role for hereditary factors in the development of this trait. Osterholm et al. provide further evidence that a gene on chromosome 3q confers susceptibility to this diabetic complication.
BACKGROUND: Vinorelbine is active and well tolerated against advanced breast cancer but there are no published efficacy studies in early breast cancer. We have therefore carried out a randomised phase III neoadjuvant trial in operable breast cancer. PATIENTS AND METHODS: Patients with > or =3 cm operable breast carcinoma were randomised to receive either vinorelbine 25 mg/m(2) on days 1 and 8 and epirubicin 60 mg/m(2) on day 1, 3 weekly for six cycles (VE) or doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) i.v. on day 1, 3 weekly for six cycles (AC), prior to standard local therapy, and adjuvant endocrine therapy as appropriate. RESULTS: A total of 451 patients were randomised. Results for AC and VE, respectively, were: overall clinical response 73% and 74%, complete clinical remission 20% and 24%, pathological complete remission 12% and 12%, mastectomy rate 52% and 55%. None of these differences were significant. Dose reduction was required in 8% for AC and 20% for VE (P <0.001) (GSCF support not used). Significantly more grade 3/4 toxicity for nausea, vomiting and alopecia (despite scalp cooling) was seen for AC compared with VE but significantly less grade 3/4 thrombophlebitis and neuropathy. CONCLUSIONS: Neoadjuvant VE is as effective as AC in early breast cancer and was better tolerated except for thrombophlebitis and neuropathy.
AIMS: Our goal was to identify genetic variants that determine the response to insulin resistance and hyperglycaemia. This report documents the diabetes syndrome of two new congenic strains of mice generated by the transfer of the Lepr(db) mutation to the FVB/NJ strain and the Lep(ob) mutation to the DBA/2J strain. METHODS: Mice were characterised by measures of blood metabolites and hormones along with challenges with glucose and insulin injections. Histological examinations of the endocrine pancreas and the kidneys were also carried out. RESULTS: Obese mice of the FVB-db congenic strain show long-term hyperglycaemia that is primarily due to severe insulin resistance. The hyperglycaemia in the fed state persists despite escalating secretion of insulin and massive increase of pancreatic beta cells. Obese FVB-db mice show evidence of mesangial matrix expansion, a hallmark of diabetic nephropathy. Leptin-deficient mice of the DBA-ob strain have variable obesity-diabetes. In mice with high insulin (>10 ng/ml), DBA-ob/ob mice maintain their increased adiposity and have a large increase in beta-cell number. In mice with low insulin (<1 ng/ml) DBA-ob/ob mice have greatly diminished adiposity. These mice have atrophied islets with evidence of increased beta-cell neogenesis from the ductal epithelium. CONCLUSIONS: The strain-specific responses suggest the existence of genetic variants that control insulin sensitivity and beta-cell responses in the strains described in this report. These new models of obesity-diabetes should prove useful in dissecting the genetic control of beta-cell responses to hyperglycaemia and insulin resistance.
Dysphagia is not infrequent in patients with connective tissue diseases such as scleroderma, polymyositis or systemic lupus erythematosus (SLE). It is usually the result of gastro-oesophageal reflux but dysmotility can equally be responsible. A case of dysphagia is described in a patient with SLE, who had developed a rare variety of bullous mucous disease affecting the whole length of oesophagus with spontaneous extrusion of an oesophageal cast. Histological features were suggestive of a variant of rare form of bullous disease in SLE called epidermolysis bullosa acquisita (EBA). This rare association of SLE and EBA involving the oesophagus has not been described in the literature.
BACKGROUND: In a previous study of Chinese men, we found that men with a higher waist-to-hip ratio (WHR) have a higher prostate cancer risk. Because leptin and insulin are related to body fat distribution, we examined whether leptin and insulin were associated with prostate cancer risk. METHODS: Blood samples were collected from 128 case patients with incident prostate cancer and from 306 healthy control subjects randomly selected from residents of Shanghai, CHINA: Epidemiologic information and anthropometric measurements were collected in personal interviews. Serum leptin, insulin, and sex hormone levels were measured by radioimmunoassay, and insulin-like growth factor-I (IGF-I) was measured by enzyme-linked immunosorbent assay. Multiple logistic regression analyses were used to estimate odds ratios for prostate cancer in relation to serum insulin and leptin levels. All statistical tests were two-sided. RESULTS: After adjustment for body mass index, WHR, IGF-I, and sex hormone levels, higher serum insulin levels were associated with a statistically significantly elevated risk of prostate cancer (P<.001). Men in the highest tertile of insulin levels had a 2.56-fold (95% confidence interval [CI] = 1.38 to 4.75) risk of prostate cancer compared with men in the lowest tertile. Regardless of the tertile level of WHR, higher serum insulin levels were associated with an increased risk of prostate cancer: Men in the highest tertiles of WHR (>0.900) and insulin (>8.83 microU/mL) had 8.55 times (95% CI = 2.80 to 26.10) the prostate cancer risk of men in the lowest tertiles of both, and those in the lowest tertile of WHR (<0.873) and highest tertile of insulin had 4.30 times (95% CI = 1.17 to 15.70) the risk. By contrast, the association between leptin levels and prostate cancer risk was not statistically significant. CONCLUSION: Our results suggest that serum insulin levels may influence the risk of prostate cancer in Chinese men. Further research, especially prospective studies, is needed to confirm these findings in high-risk populations and to clarify the underlying mechanisms involved.
OBJECTIVES: To investigate the effect of oral misoprostol in dosages varying from 200 microg to 800 microg on postpartum uterine contractility and to establish their side effects. DESIGN: A prospective descriptive study. PARTICIPANTS: Fifty-seven women who delivered vaginally after spontaneous labours not requiring augmentation. METHODS: Within 5 minutes of delivery of the placenta, a calibrated Gaeltec catheter with an intrauterine pressure transducer at its tip was inserted transcervically into the uterine cavity. Cumulative uterine activity was recorded for 30 minutes in each woman before administering the oral misoprostol tablets and continued for a further 90 minutes after its administration. Thus each woman acted as her own control regarding changes in uterine contractility. Uterine activity was recorded on a Sonicaid Meridian fetal monitor, which measures active contraction area automatically. The incidence of side effects was also recorded. RESULTS: There was no statistical difference (P = 0.887) in the adjusted mean difference in cumulative uterine activity following all the doses of oral misoprostol, compared with intramuscular syntometrine, the largest difference being seen in oral misoprostol 200 microg (adjusted mean difference -2282 kPas s, 95% CI -7954 to 3390 kPas s). The mean onset of action of oral misoprostol (6.1, SD 2.1 min) was significantly slower than that of intramuscular syntometrine (3.2, SD 1.5 min; P = 0.002), but their durations of action were similar (P = 0.637). In the misoprostol group the commonest side effects were shivering (36%) and a rise in body temperature above 38 degrees C (40%). In the syntometrine group, the most commonly observed side effect was moderate uterine pain (nine out of ten women) and a rise in diastolic blood pressure of 20 mmHg (two out of ten women). CONCLUSION: The results of this study show that oral misoprostol has a definite uterotonic effect on the postpartum uterus. At doses of 200 microg to 400 microg, oral misoprostol has a similar uterotonic effect to intramuscular syntometrine. Higher doses of oral misoprostol are associated with significantly more side effects.
OBJECTIVE: To determine whether cervical membrane sweeping (stripping) during induction of labor is beneficial. METHODS: We compared outcomes of labor after induction in pregnant women at term in a randomized trial. Women were assigned to having their membranes swept or not during induction. Outcome measures included duration of labor, maximum dose of oxytocin used, induction-labor interval, and mode of delivery. RESULTS: We recruited 130 nulliparas (64 sweep, 66 nonsweep) and 118 multiparas (60 sweep, 58 nonsweep). Among nulliparas who received intravaginal prostaglandin (PG) E(2) and oxytocin, those who had simultaneous sweeping had significantly shorter mean (+/- standard error of mean) induction-labor interval (13.6 +/- 1.4 versus 17.3 +/- 1.2 hours, P =.048), lower mean maximum dose of oxytocin (6.8 +/- 0.8 versus 10.35 +/- 1.1 mU/minute, P =.01), and increased normal delivery rates (vaginal delivery 83. 3% versus 58.2%, P =.01). Sweeping also had a favorable effect on nulliparas who received oxytocin alone (mean induction-labor interval 5.8 +/- 3.1 versus 11.2 +/- 3.6 hours, P =.04; mean maximum dose 8.8 +/- 1.3 versus 16.3 +/- 1.9 mU/min, P =.01). Those differences were limited to women with unfavorable cervices. There were no differences in any outcome measures in multiparous women. CONCLUSION: Sweeping of the membranes during induction of labor had a beneficial effect on labor and delivery, which appeared to be limited to nulliparas with unfavorable cervices who needed cervical priming with PGE(2).
OBJECTIVE: To determine whether there is a difference in peripheral vascular reactivity between normal women and those with pregnancy-induced hypertension. METHODS: Capillary blood flow (flux) was recorded in the skin over the ankle in 26 pregnant women with pregnancy-induced hypertension at term. Twelve of these women had proteinuria, and 14 were nonproteinuric. Leg lowering was used to activate the venoarteriolar reflex, and the resultant change in flux, expressed as a percentage change from the baseline, was used as an index of vascular reactivity. The results were compared with those of a control group comprising 23 matched normotensive women. The study was repeated on all of the women after delivery. RESULTS: Women with hypertension showed a median (range) increase in flux of +24.4% (-15.5% to +151.1%), significantly different from controls: -39.3% (-80.9% to -4.3%, P <.001). This difference persisted regardless of the presence or absence of proteinuria. Responses in women with pregnancy-induced hypertension were significantly different after delivery (median -60.7%; range -158.5% to -19.5%, P <.001) when compared with predelivery responses. Similar changes as a result of delivery were seen in women with proteinuric (medians +25.9% and -57. 9%, P <.002) and nonproteinuric (medians +7.8% and -62.8%, P <.001) hypertension but not in controls. Postdelivery responses in women with hypertension were no different from those of controls. CONCLUSION: Women with pregnancy-induced hypertension have abnormal cutaneous vascular reactivity that returns to normal after delivery.
OBJECTIVE: To assess the fetal metabolic effects of intrapartum maternal tocolysis with terbutaline in the presence of fetal heart rate abnormalities, with a special emphasis on lactate concentration, in view of its potential use as a marker of fetal condition. DESIGN: Descriptive study. SETTING: Two labour wards, National University Hospital, Singapore, and Ostersund Hospital, Sweden. METHODS: Eight parturients with abnormal intrapartum fetal heart rate recordings were given bolus i.v. injection of 0.25 mg terbutaline and monitored both before and 20 minutes after treatment. RESULTS: Maternal venous glucose increased from 5.0 (0.9) (mean (SD)) to 5.6 (1.2) mmol/l (p=0.002) and fetal scalp blood glucose rose from 4.1 (1.8) to 4.7 (1.4) mmol/l (p=0.009) 20 minutes after the injection. No significant change was found in maternal or fetal lactate concentrations. CONCLUSION: Terbutaline tocolysis for "intrauterine resuscitation" does not affect fetal lactate concentration 20 minutes after treatment.
Transgenic technology allows the ability to target regulatory genes to the lungs in a cell-specific fashion. Using this technology, we have generated a model to investigate the phenotypic consequences of targeting oncogenes to particular cell types in the lungs and are developing a second model for the regulated expression of oncogenes in the lung. The transgenic model involves the constitutive expression of simian virus 40 large T antigen in the Clara cells of mouse lungs. This model has been used to investigate changes in expression of cell cycle regulatory genes in the Clara cells during the transformation process, as well as the expression of the transcription factors regulating the expression of Clara cell differentiation markers. The second model we are developing investigates the regulated expression of the genes in the lungs. This system is based on the establishment of two types of transgenic lines. The regulator line consists of a chimeric transcriptional factor placed under the control of a lung-specific SPC (surfactant protein C) promoter. This chimeric regulator is composed of a transcription activation domain, the GAL4 DNA-binding domain, and a truncated progesterone receptor that is responsive to RU 486, but not to endogenous progesterone. The second transgenic mouse line contains the silent target transgene under the control of a minimal promoter with upstream activating sequences (UAS) that are recognized by the regulator transgene. Upon breeding these two lines, the resulting bitransgenic mice can then be induced to express the target transgene only with the administration of RU 486. Two generations of regulators have been evaluated on their ability to regulate the expression of a growth hormone reporter gene. This system demonstrated the inducible expression of the reporter genes in the distal airways of the lungs.
UNLABELLED: Fetal pulse oximetry has been advocated as a means of improving the specificity of cardioto-cography in intrapartum fetal surveillance. The objective of this article, the first of two reviewing the current literature on fetal pulse oximetry, is to discuss the principles of this new and evolving technology, its development, and the various factors that can affect its readings during fetal monitoring. It serves as a prelude to the second article, which profiles the clinical application of fetal pulse oximetry. Literature pertaining to this topic was selected from a MEDLINE search from 1965 through September 1999, with additional sources obtained through cross-referencing. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to explain the principles of fetal pulse oximetry, and describe the factors that affect the calibration of fetal pulse oximeters and the factors that affect the fetal pulse oximeter readings.
UNLABELLED: Part II continues by discussing the clinical application of fetal pulse oximetry in intrapartum fetal surveillance as reviewed in the literature. It profiles the predictive ability of fetal pulse oximetry and its correlation with conventional methods of fetal monitoring. In addition, an account is made of its limitations, safety, and acceptability in clinical practice. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to describe the predictive abilities of fetal pulse oximetry and its correlation with conventional methods of fetal monitoring, to define the critical threshold of fetal oxygen saturation, and to summarize the safety of fetal pulse oximetry.
The Koletsky ("corpulent) obese rat is homozygous for an autosomal recessive mutation of the leptin receptor (Lepr) that results in hyperphagia, obesity, and hyperlipidemia. Unlike the Lepr mutation that characterizes the fatty Zucker rat (Lepr(fa)), the Koletsky mutation (Lepr(fak)) is null. Because the Lepr(fak) mutation is null, exogenous leptin should have no effect on body weight or food intake in fa(k)/fa(k) rats. We confirmed that prediction: murine leptin, administered into the third ventricle for 5 consecutive days, did not affect daily food intake or body weight in fa(k)/fa(k) rats but produced dose-related inhibitions of food intake and body weight in +/+ and +/fa(k) rats. Although fa(k)/fa(k) rats did not respond to leptin, their response to CCK-8 (4 microg/kg ip) injected before 30-min test meals of 10% sucrose was not different from that of +/+ or +/fa(k) rats. These results demonstrate that the fa(k)/fa(k) rat is a good model in which to analyze the controls of food intake, energy expenditure, and energy storage in the absence of leptin effects.
Atrial septal aneurysm (ASA) is a rare congenital anomaly. It may occur as an isolated pathology or in association with other cardiovascular lesions such as mitral valve disease, atrial septal defect, and others. The diagnosis of ASA became more widely recognized with the use of 2-dimensional echocardiography. Three-dimensional echocardiography is a recently developed imaging technique. It can be used as an adjunct to conventional transesophageal echocardiography. Images of different aspects of cardiac chambers and valves can be obtained with 3-dimensional echocardiography. This paper reports on 2 cases of different types of ASA imaged by 3-dimensional echocardiography. The images were obtained from the left and right atriums, respectively. The 3-dimensional image taken from the left atrium showed the ASA to be a localized concave structure, and the 3-dimensional image taken from the right atrium showed the ASA to be a localized bulging structure. Our pictures are the first reported 3-dimensional echocardiographic images of ASA. We hope this report will allow for a more comprehensive understanding of its pathology.
The aim of this study was to obtain data on the outcomes of chronic hemodialysis patients who underwent percutaneous transluminal coronary angioplasty (PTCA). A retrospective chart analysis identified 31 such patients between August 1992 and October 1996. The mean follow-up period was 12.4 +/- 11.7 months. Angiographic success was achieved in 39 of 41 (95.1%) stenoses attempted. There were three in-hospital deaths. Clinical success was achieved in 28 of 31 patients (90%). Two of the 28 survivors were lost to follow-up. Recurrent angina developed within 6 months in 14 of 26 patients (53.8%). Eleven and 17 of the 26 patients (42.3% and 65.4%) died within 6 and 14 months, respectively, after the PTCA procedure. Ten of the 17 deaths (58.8%) were due to cardiovascular events. Our study suggests that PTCA is technically feasible with high angiographic success rate in chronic hemodialysis patients. In-hospital mortality rate and rate of recurrent angina are high. Long-term prognosis is poor.
OBJECTIVE: To measure the ease of use of a fetal pulse oximeter in a busy labour ward. DESIGN: Descriptive study in the Labour Ward, National University Hospital, Singapore, involving 145 labouring women with singleton pregnancies, and fetuses in cephalic presentation, with cervical dilatation >2 cm and amniotic membranes ruptured. RESULTS: Placement was comfortable. Oxygen saturation (SpO2) readings were obtained in 127 women (87.5%). Adequate readings were obtained a median of 69% of the time the transducer was in situ. SpO2 values in the last 10 min prior to delivery correlated poorly with parameters of neonatal outcome. CONCLUSION: The Nellcor N-400 fetal pulse oximeter and FS14 fetal sensor is a feasible method of intrapartum fetal monitoring in a busy labour ward and is acceptable to labouring women.
This study aimed to establish the normal range of umbilical artery pH, pCO2, base deficit and lactate in normal term and preterm newborn. Umbilical artery pH, pCO2, base deficit and lactate was measured in 637 newborn babies. The study included 555 babies at term with Apgar score equal to or more than 7 at 5 minutes, not requiring assisted ventilation and not admitted to the neonatal unit (NNU), as well as 47 preterm babies with Apgar score equal to or more than 7 at 5 minutes who were admitted to the NNU for observation only because of prematurity. Data was presented as mean and SD. Statistical analysis was done by t-test and simple linear regression analysis. In the newborn at term mean umbilical artery blood gas and lactate were as follows; pH = 7.25 (+/- 0.08), pCO2 = 45.66 (+/- 1.88) mmHg, base deficit = 7.69 (+/- 3.88) mEq/L, lactate = 2.96 (+/- 1.8) mMol/L. In preterm newborn the values were; pH = 7.25 (+/- 0.04), pCO2 = 51.78 (+/- 13.00) mmHg, base deficit = 5.29 (+/- 1.87) mEq/L, lactate = 2.55 (+/- 1.87) mMol/L. The range of umbilical artery blood gas and lactate parameters in term and preterm fetuses with good neonatal outcome were derived. There was a statistically significant difference in pCO2 and base deficit between term and preterm newborn. There was no linear correlation between lactate, pH, pCO2, base deficit and fetal glucose respectively in term or preterm infants.
The interrelationships between lactate, lactate/pyruvate (L/P) ratio and catecholamines (CA) in cord artery and vein blood were studied in 56 pregnancies who had complications in the antenatal period or during labour. This group of babies had higher CA levels and were more acidaemic than fetuses after normal pregnancies and labour. There were stronger correlations between lactate and noradrenaline (NA) (R = 0.56, P < 0.001), adrenaline (A) (R = 0.41, P = 0.002) and dopamine (DA) (R = 0.42, P = 0.001) in cord artery blood, than previously reported for normal deliveries. Correlations between L/P ratio and CAs were also significant, although weaker. Multiple regression analysis, using cord artery lactate as the dependent variable, revealed significant correlations for pH (P = 0.01) and pyruvate (P < 0.001) but not for the CAs. The subgroups with high lactate (> 75th centile) had significantly higher NA (P = 0.007) and DA (P < 0.001) in cord artery and NA (P < 0.001) and A (P < 0.001) in cord vein blood, as compared with the subgroup who had lower lactate concentrations. We conclude that fetal hypoxia induces fetal CA production as well as anaerobic metabolism with lactate production. However, the adrenergic stimulation seems not to contribute significantly to the fetal lactate production.