Proton and molecular permeation through the basal plane of monolayer graphene oxide.

Two-dimensional (2D) materials offer a prospect of membranes that combine negligible gas permeability with high proton conductivity and could outperform the existing proton exchange membranes used in various applications including fuel cells. Graphene oxide (GO), a well-known 2D material, facilitates rapid proton transport along its basal plane but proton conductivity across it remains unknown. It is also often presumed that individual GO monolayers contain a large density of nanoscale pinholes that lead to considerable gas leakage across the GO basal plane. Here we show that relatively large, micrometer-scale areas of monolayer GO are impermeable to gases, including helium, while exhibiting proton conductivity through the basal plane which is nearly two orders of magnitude higher than that of graphene. These findings provide insights into the key properties of GO and demonstrate that chemical functionalization of 2D crystals can be utilized to enhance their proton transparency without compromising gas impermeability.

[Pre- and post-diagnosis body mass index in association with colorectal cancer death in a prospective cohort study].

Objective: To evaluate the association between pre-and post-diagnosis body mass index (BMI) and risk of colorectal cancer (CRC) death. Methods: The cohort consisted of 3, 057 CRC patients from Shanghai who were diagnosed from Jan. 1, 2009 to Dec. 31, 2011 and aged from 20 to 74 years. The pre- and post-diagnosis BMI and clinical and lifestyle factors were collected at baseline. Death information was collected using record linkage with the Shanghai Cancer Registry and telephone confirmation during follow-up by the end of 2019. The Cox proportional regression model was used to estimate HR with 95% CI. Results: Analysis by multivariable Cox model showed no association between pre-diagnosis BMI and death risk in both male and female patients. Male patients with a post-diagnosis underweight BMI had an elevated risk of death compared to those in normal weight (HR=1.69, 95% CI: 1.21-2.37), especially in early stage cases. Overweight patients (HR=0.74, 95% CI: 0.61-0.89) and patients with obesity class Ⅰ (HR=0.63, 95% CI: 0.45-0.89)had better survival with decreased risks of death, especially in advanced stage cases. The decreased death risk in patients with obesity class Ⅱ was not significant (HR=0.57, 95% CI: 0.24-1.39). The P(trend) value for decreased risk of death with increased BMI in female patients was statistically significant (P<0.001), and the overweight and obesity class Ⅰ categories had better survival in advanced stage(HR(overweight)=0.62, 95% CI: 0.42-0.93; HR(obesity class Ⅰ)=0.39, 95% CI: 0.16-0.98). Both male and female patients with post-diagnosis BMI loss >2.0 kg/m(2) had an increased death risk when compared with those with stable BMI (change≤1.0 kg/m(2)) between pre- and post-diagnosis. BMI gain after diagnosis did not change death risk. Conclusions: Post-diagnosis BMI in the overweight or obesity class Ⅰ groups might be conducive to prolonging male CRC patients' survival, while underweight might result in poor prognosis. Keeping weight and avoiding excessive weight loss should be suggested for all CRC patients after diagnosis.

[Progress on development and application of the diet-related inflammatory index in cancer epidemiological studies].

Cancer is a major public health problem worldwide, causing an more serious burden of disease. Inflammation is considered a predisposing factor for cancer with close relationship with its incidence. In recent years, the public and epidemiologists has paid more attention to the association between nutrition and cancer and other chronic diseases in the perspective of inflammation. This paper summarizes the development and application of the diet-related inflammatory index in cancer epidemiological studies based on the literature retrieval of common diet-related inflammatory index. Firstly, we highlight the common diet-related inflammatory indices and their construction methods, such as the Dietary Inflammatory Index, a literature-derived diet-related inflammatory index, and the Empirical Dietary Inflammatory Index, an empirically derived diet-related inflammatory index, and so on. Secondly, the epidemiological research progress on the commonly used diet-related inflammatory indices is briefly introduced. Finally, the advantages and disadvantages of the two types of this inflammatory indices are also briefly described for the purpose of providing reference for nutrition epidemiological studies of cancer and other chronic diseases in China.

[Statistical methods for relative risk estimation and applications in case-cohort study].

Objective: To systematically introduce the design of case-cohort study and the statistical methods of relative risk estimation and their application in the design. Methods: First, we introduced the basic principles of case-cohort study design. Secondly, Prentice's method, Self-Prentice method and Barlow method were described in the weighted Cox proportional hazard regression models in detail, finally, the data from the Shanghai Women's Health Study were used as an example to analyze the association between obesity and liver cancer incidence in the full cohort and case-cohort sample, and the results of parameters from each method were compared. Results: Significant association was observed between obesity and risk for liver cancer incidence in women in both the full cohort and the case-cohort sample. In the Cox proportional hazard regression model, the partial regression coefficients of the full cohort and the case-cohort sample fluctuated with the adjustment of confounding factors, but the hazard ratio estimates of them were close. There was a difference in the standard error of the partial regression coefficient between the full cohort and the case-cohort sample. The standard error of the partial regression coefficient of the case-cohort sample was larger than that of the full cohort, resulting in a wider 95% confidence interval of the relative risk. In the weighted Cox proportional hazard regression model, the standard error of the partial regression coefficient of Prentice's method was closer to the parameter estimates from full cohort than Self-Prentice method and Barlow method, and the 95% confidence interval of hazard ratio was closer to that of the full cohort. Conclusions: Case-cohort design could yield parameter results closer to the full cohort by collecting and analyzing data from sub-cohort members and patients with the disease, and reduce sample size and improve research efficiency. The results suggested that Prentice's method would be preferred in case-cohort design.

[Application of dual-channel contrast-enhanced ultrasound in classification of hilar cholangiocarcinoma and diagnosis of etiology of low biliary obstruction].

Objective: To investigate the clinical value of dual-channel contrast-enhanced ultrasound (DCUS) in the classification of hilar cholangiocarcinoma and the diagnosis of the etiology of low obstructive jaundice. Methods: The data of 114 patients with obstructive jaundice examined by the Department of Ultrasound of Lanzhou University Second Hospital from October 2018 to February 2020 were retrospectively collected. There were 60 males and 54 females, aged 37~84 (63±10) years. All patients underwent preoperative transvenous contrast-enhanced ultrasound (CEUS), intraoperative puncture needles, postoperative ultrasound-guided percutaneous transhepatic cholangiocarcinography (UG-PTC) and three-dimensional ultrasound cholangiography (3D-USC) through an external drainage tube, known as DCUS. The classification of hilar cholangiocarcinoma and the nature of low biliary tract obstruction were determined according to the characteristics of DCUS images. All patients who have received DCUS underwent magnetic resonance cholangiopancreatography (MRCP) and X-ray cholangiography. X-ray cholangiography was used as the gold standard for classification of hilar cholangiocarcinoma, and the accuracy of US, CEUS and DCUs was analyzed. Low obstructive jaundice was characterized by surgical pathology as the gold standard, and the diagnostic efficacy of conventional ultrasound (US), CEUS and DCUs was analyzed. At the same time, the receiver operating characteristic (ROC) curve was used to compare the efficacy of MRI+MRCP and DCUS in determination of the nature of low biliary obstruction. Results: The coincidence rates of US, CEUS, and DCUS in the classification of hilar cholangiocarcinoma and X-ray cholangiography were: 75.6% (34/45), 82.2% (37/45), and 93.3% (42/45), respectively. The coincidence rates of US, CEUS, and DCUS in the determination of the nature of low biliary obstruction and surgical pathology were 56.5% (39/69), 82.6% (57/69), and 85.5% (59/69), respectively. Compared with conventional ultrasound, CEUS had no statistically significant difference in the diagnosis of hilar cholangiocarcinoma (P=0.438), and DCUS had statistically significant difference in the diagnosis of hilar cholangiocarcinoma (P=0.039).ROC curve analysis suggested that the cut-off value of MRI+MRCP grade and DCUS grade for diagnosing benign and malignant low biliary obstruction were both 2.5; the area under the curve (AUC) were 0.897 and 0.906, respectively (both P<0.01); sensitivity were 77.5% and 93.1%, respectively; and the specificity were 87.5% and 82.8%, respectively. Conclusion: The value of DCUS in the classification of hilar cholangiocarcinoma and the qualitative diagnosis of low biliary tract obstruction was comparable to that of X-ray cholangiography and MRCP. DCUS had important clinical application value in the classification of hilar cholangiocarcinoma and the etiological diagnosis of low obstructive jaundice.

Erythroderma (exfoliative dermatitis). Part 2: energy homeostasis and dietetic management strategies.

Erythroderma (exfoliative dermatitis) is associated with important metabolic changes that include an enhancement in energy expenditure. The key components to total energy expenditure (TEE) include basal metabolic rate (~68% of TEE), physical activity (~22% of TEE) and thermic effect of food (~10% of TEE). In the erythrodermic state, there are likely multiple contributors to the increase in basal metabolic rate, such as 'caloric drain' resulting from increased evaporation of water from enhanced transepidermal water loss, increased activity of the cardiovascular system (including high-output cardiac failure), increased nonshivering thermogenesis and hormonal changes such as hypercortisolaemia. A change in the patient's level of physical activity and appetite as a result of ill health status may further impact on their TEE and energy consumption. In Part 2 of this two-part concise review, we explore the key constituents of energy homeostasis and the potential mechanisms influencing energy homeostasis in erythroderma, and suggest much-needed dietetic management strategies for this important condition.

Erythroderma (exfoliative dermatitis). Part 1: underlying causes, clinical presentation and pathogenesis.

Erythroderma (exfoliative dermatitis), first described by Von Hebra in 1868, manifests as a cutaneous inflammatory state, with associated skin barrier and metabolic dysfunctions. The annual incidence of erythroderma is estimated to be 1-2 per 100 000 population in Europe with a male preponderance. Erythroderma may present at birth, or may develop acutely or insidiously (due to progression of an underlying primary pathology, including malignancy). Although there is a broad range of diseases that associate with erythroderma, the vast majority of cases result from pre-existing and chronic dermatoses. In the first part of this two-part concise review, we explore the underlying causes, clinical presentation, pathogenesis and investigation of erythroderma, and suggest potential treatment targets for erythroderma with unknown causes.

To build a prognostic score model containing indispensible tumour markers for metastatic nasopharyngeal carcinoma in an epidemic area.

BACKGROUND AND OBJECTIVE: The survival outcomes of patients with metastatic nasopharyngeal carcinoma (NPC) differ significantly between individuals. The aim of this study is to build a prognostic score model (PSM) incorporating circulating tumour markers for metastatic NPC in an epidemic area. METHODS: Seven hundred and ninety-nine patients with disseminated NPC were analysed retrospectively. Univariate and multivariable analyses were conducted using the Cox proportion hazards model. Factors analysed included patients' characteristics (gender, age group, performance status), circulating tumour-marker characteristics (Epstein-Barr virus (EBV) DNA level, EBV VCA-IgA level, lactate dehydrogenase (LDH) level, alkaline phosphatase (ALP) level), basic laboratory characteristics (leucocyte count, haemoglobin level, albumin level), and disease characteristics (presence of metastasis at presentation, disease-free interval, number of metastatic sites, specific metastatic sites). The PSM was built according to numerical score derived from the regression coefficients of each independent prognostic variable. The prognostic score of each patient was calculated by totalling up the scores of each independent variable. RESULTS: Independent prognostic factors included performance status, age, haemoglobin level, LDH level, ALP level and EBV DNA level. Three prognostic groups based on PSM were obtained: low risk (total score=0-4); intermediate risk (5-8); high risk (9-12). Median survivals of the three groups were 25.5, 15.1 and 7 months, respectively, (P<0.001). CONCLUSION: Clinical and laboratory characteristics can help guide the prognostication of patients with metastatic NPC in epidemic areas.

Reduced left atrial function on exercise in patients with heart failure and normal ejection fraction.

AIMS: The cardinal symptom of heart failure with a normal ejection fraction (HFNEF) is exertional dyspnoea. The authors hypothesised that failure of left atrial (LA) compensatory mechanism particularly on exercise contributes to the genesis of symptoms in HFNEF patients. METHODS AND RESULTS: Fifty HFNEF patients, 15 asymptomatic hypertensive subjects and 30 healthy controls underwent rest and submaximal exercise echocardiography. Rest and exercise systolic, early diastolic and late diastolic (Am) mitral annular velocities were assessed using colour tissue Doppler echocardiography. Left atrial functional reserve index was calculated. Am at rest was comparable between all three groups, but exercise Am was significantly lower in HFNEF compared with hypertensive subjects and healthy controls resulting in a lower LA functional reserve index (0.84 (1.34) vs 2.39 (1.27) and 1.81 (1.39), p<0.001). LA volume index was significantly higher in HFNEF patients (30.4 (9.2) vs 27.9 (6.3) and 23.2 (7.1) ml/m(2), p=0.002). There was a significant correlation between Am on exercise with peak VO(2) max (r=0.514, p<0.001) and E/Em on exercise (r=-0.547, p<0.001). Area under the receiver operating characteristic for Am on exercise was 0.768 (95% CI=0.660 to 0.877). CONCLUSION: HFNEF patients have reduced LA function on exercise in addition to left ventricular systolic and diastolic dysfunctions. Reduced LA function probably contributes significantly to exercise intolerance and breathlessness in HFNEF patients.

Exploring the potential of a highly compressible microcrystalline cellulose as novel tabletting excipient in the compaction of extended-release coated pellets containing an extremely water-soluble model drug.

Compaction of controlled-release coated pellets into tablets is challenging because of the fusion of pellets and the rupturing of coated film. The difficulty in compaction intensifies with the use of extremely water-soluble drugs. Therefore, the present study was conducted to prepare and compact pellets containing pseudoephedrine hydrochloride as an extremely water-soluble model drug. The pellets were produced using an extrusion-spheronization technique. The drug-loaded pellets were coated to extend the drug release up to 12-h employing various polymers, and then they were compressed into tablets using microcrystalline cellulose Ceolus KG-801 as a novel tabletting excipient. The in vitro drug release studies of coated pellets and tablets were undertaken using the USP basket method in dissolution test apparatus I. The amount of drug released was analyzed at a wavelength of 215 nm. The combined coatings of hydroxypropyl methylcellulose and Kollicoat SR-30D yielded 12-h extended-release pellets with drug release independent of pH of dissolution medium following zero-order kinetics. The drug release from the tablets prepared using inert Celous KG-801 granules as tabletting excipient was found faster than that of coated pellets. However, a modification in drug release rate occurred with the incorporation of inert Ceolus KG-801 pellets. The drug dissolution profile from tablets containing 40% w/w each of coated pellets and inert granules along with 20% w/w inert pellets was found to be closely similar to that of coated pellets. Furthermore, the friability, tensile strength, and disintegration time of the tablets were within the USP specifications.

Hypertension and heart failure: a dysfunction of systole, diastole or both?

The pathological myocardial hypertrophy associated with hypertension contains the seed for further maladaptive development. Increased myocardial oxygen consumption, impaired epicardial coronary perfusion, ventricular fibrosis and remodelling, abnormalities in long-axis function and torsion, cause, to a varying degree, a mixture of systolic and diastolic abnormalities. In addition, chronotropic incompetence and peripheral factors such as lack of vasodilator reserve and reduced arterial compliance further affect cardiac output particularly on exercise. Many of these factors are common to hypertensive heart failure with a normal ejection fraction as well as systolic heart failure. There is increasing evidence that these apparently separate phenotypes are part of a spectrum of heart failure differing only in the degree of ventricular remodelling and volume changes. Furthermore, dichotomizing heart failure into systolic and diastolic clinical entities has led to a paucity of clinical trials of therapies for heart failure with a normal ejection fraction. Therapies aimed at reversing myocardial fibrosis, and targets outside the heart such as enhancing vasodilator reserve and improving chronotropic incompetence deserve further study and may improve the exercise capacity of hypertensive heart failure patients. Hypertension heart disease with heart failure is simply not a dysfunction of systole and diastole. Other peripheral factors including heart rate and vasodilator response with exercise may deserve equal attention in an attempt to develop more effective treatments for this disorder.

Investigation of interpolymer complexation between Carbopol and various grades of polyvinylpyrrolidone and effects on adhesion strength and swelling properties.

PURPOSE: To investigate the interpolymer complexation between Carbopol 934P (CP) and various grades of polyvinylpyrrolidone (PVP) (K90, K32, C15, and VA/S-630). METHODS: Amount of fresh and dried CP-PVP complexes, water retaining capacity, apparent density, pH, conductivity, FTIR, swelling and adhesion strength were studied. RESULTS: Interpolymer complexation occurred between CP and all the PVP, but most significantly with PVP K90. Maximum amount of fresh and dried CP-PVP K32 complexes were obtained at a weight ratio of 1:1. On the contrary, CP concentration was linearly related to amount of CP-PVP K90 complexes produced and their water retaining capacity were all above 97%. Increase in CP concentration caused a decrease in pH, but an increase in conductivity for all the CP-PVP complexes. The apparent density of the filtrate of CP-PVP K90 complex was the lowest and its IR spectrum was similar to that of pure PVP K90, indicating that all the CP has interacted with the PVP K90. Discs of physical mixtures of CP-PVP K90 swelled gradually and reached a maximum after 20-30 hr, while discs of solid complex swelled readily and reached a maximum within 20 hr. Adhesion strength was directly correlated to CP content. However, adhesion strength of solid CP-PVP K90 complex was lower than the physical mixture of the pure polymers. CONCLUSION: Interpolymer complexation occurred between CP and PVP but to a different extent for the various grades of PVP. Complexation was most prominent between CP and PVP K90.

A window on the current status of diabetes mellitus in Singapore--the Diabcare-Singapore 1998 study.

The Diabcare-Singapore project was carried out in 22 clinics (general hospitals, GH and primary healthcare centres, PHC) to provide an overview of diabetes management and metabolic control status. Data from 1697 diabetic patients were collected on paper forms and analysed centrally. Type 2 diabetes mellitus patients constituted 91.4% and type I patients constituted 8.1% of population. The proportion of type I patients was greater in GH (18.1%) vs PHC (3.4%). The mean age (+/- SD) was 58.1 +/- 14.4 years and mean duration of diabetes was 10.1 +/- 7.5 years. Mean body mass index (BMI) was 25.1 +/- 4.4 kg/m2 and more than half (53%) of patients were overweight (BMI >25 kg/m2). Mean HbA1c and FBG levels were 8.0 (1.9% and 9.1 +/- 3.1 mmol/l. A total of 51% of patients had HbA1c (1% above the Upper Limits of Normal (ULN). Fasting blood glucose (FBG) was >7.8 mmol/l in 61% of patients. The majority (70%) had satisfactory levels of fasting lipids (triglycerides, total cholesterol and HDL-cholesterol). Only 19.7% practised home blood glucose self-monitoring, while 99% reported receiving some diabetes education. Sixteen percent of patients had abnormal levels of protein (>500 mg/24 h) in the urine, 3% had elevated serum creatinine levels and 36% had microalbuminuria. Retinopathy (12%), cataract (16%) and neuropathy (12%) were commonly reported diabetic complications. The data revealed suboptimal glycaemic control in about half of patients studied.

The status of diabetes mellitus in primary care institution and restructured hospitals in Singapore.

The Diabcare-Asia Singapore 1998 project was carried out using data from 22 centres collected on paper forms to provide an overview of diabetes management and metabolic control status in 1697 diabetic patients from both primary health care clinic (PHC) (67%) and restructured hospital (RH) (33%) settings. PHC patients were on average older than RH patients (61.3 +/- 11.2 years vs 51.5 +/- 17.7 years), and had a shorter duration of diagnosed diabetes (9.2 +/- 6.8 years vs 12.0 +/- 8.5 years). The mean body mass index (BMI) for PHC patients was 25.5 +/- 4.4 kg/m2 vs 24.5 +/- 4.2 kg/m2 for RH patients. Proportionately more PHC than RH patients were overweight (BMI >25 kg/m2) (49% vs 42%). Patients with type I diabetes constituted 3.5% of PHC vs 18.1% of the RH cohort. HbA1c information was available for 92.5% of RH vs 69% of PHC patients. HbA1c measurements were <1% above ULN in 50% of PHC vs 37% of RH patients, while FBG was >7.8 mmol/l in >61% of all patients. Proteinuria (>500 mg/24 hrs) was reported in 13% of PHC vs 26% of RH patients tested. Microalbuminuria (20-300 mg/l) was noted in 36% of 171 RH patients tested. Oral hypoglycaemic agents were used as sole therapy in 83.5% of PHC vs 43% of RH patients. Eye, feet, renal and severe late complications were more commonly reported by RH than PHC patients. There is a variation in the patient profiles and care between PHC and RH patients.

Molecular strategies for overcoming antibiotic resistance in bacteria.

Overuse of antibiotics in humans and livestock has led to the rapid evolution of bacteria that are resistant to multiple drugs such that even vancomycin, the drug of last resort, is no longer effective against some strains. Apart from the discovery and exploitation of the natural peptide antimicrobial agents that form part of the innate immune systems of plants and animals, there have been few new antibiotics developed in recent years. Here we review strategies designed to exploit recent advances in molecular biology, including recombinant DNA technology, molecular modelling and genomics to develop new antibacterial agents that overcome antibiotic resistance.

Effect of Carbopol and polyvinylpyrrolidone on the mechanical, rheological, and release properties of bioadhesive polyethylene glycol gels.

This study examined the mechanical (hardness, compressibility, adhesiveness, and cohesiveness) and rheological (zero-rate viscosity and thixotropy) properties of polyethylene glycol (PEG) gels that contain different ratios of Carbopol 934P (CP) and polyvinylpyrrolidone K90 (PVP). Mechanical properties were examined using a texture analyzer (TA-XT2), and rheological properties were examined using a rheometer (Rheomat 115A). In addition, lidocaine release from gels was evaluated using a release apparatus simulating the buccal condition. The results indicated that an increase in CP concentration significantly increased gel compressibility, hardness, and adhesiveness, factors that affect ease of gel removal from container, ease of gel application onto mucosal membrane, and gel bioadhesion. However, CP concentration was negatively correlated with gel cohesiveness, a factor representing structural reformation. In contrast, PVP concentration was negatively correlated with gel hardness and compressibility, but positively correlated with gel cohesiveness. All PEG gels exhibited pseudoplastic flow with thixotropy, indicating a general loss of consistency with increased shearing stress. Drug release T50% was affected by the flow rate of the simulated saliva solution. A reduction in the flow rate caused a slower drug release and hence a higher T50% value. In addition, drug release was significantly reduced as the concentrations of CP and PVP increased because of the increase in zero-rate viscosity of the gels. Response surfaces and contour plots of the dependent variables further substantiated that various combinations of CP and PVP in the PEG gels offered a wide range of mechanical, rheological, and drug-release characteristics. A combination of CP and PVP with complementary physical properties resulted in a prolonged buccal drug delivery.

Simple high-performance liquid chromatographic method for simultaneous determination of fusidic Acid and betamethasone dipropionate in a cream formulation.

A simple and selective high-performance liquid chromatography (HPLC) method using ultraviolet detection was developed for simultaneous determination of fusidic acid and betamethasone dipropionate in a cream formulation. A Supelcosil LC18 column was used for chromatographic separation. The mobile phase consisted of acetonitrile and 0.01 M disodium hydrogen orthophosphate (70:30, % v/v) adjusted to pH 6 with glacial acetic acid. Analysis was run at a flow rate of 1.0 mL/minute with the detector operating at 235 nm. The standard calibration curve was linear over a concentration range of 0.3 to 1.2 mg/mL for fusidic acid and 9.6 to 38.4 micrograms/mL for betamethasone dipropionate. The average recovery values for fusidic acid and betamethasone dipropionate were almost 100%. The within-run and between-run coefficient of variation and percent error values for the two drugs were all less than 2% and +/- 3%, respectively.

Mixed polymer coating for modified release from coated spheroids.

Modified-release drug spheroids coated with an aqueous mixture of high-viscosity hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) were formulated. The preparation of core drug spheroids and the coating procedures were performed using the rotary processor and a bottom-spray fluidized bed, respectively. Dissolution studies indicated that incorporation of suitable additives, such as poly(vinylpyrrolidone) (PVP) and poly(ethylene glycol) 400 (PEG) improved the flexibility and integrity of the coat layer by retarding the drug release. An increase in coating levels applied generally retarded the release rate of the drug. However, the ratio of HPMC to NaCMC in the mixed, plasticized polymeric coat played a more dominant role in determining the dissolution T50% values. The optimal ratio of HPMC to NaCMC for prolonged drug release was found to be 3:1, whereas an increase in the amount of NaCMC in the mixed polymer coat only increased drug release. The synergistic viscosity effect of HPMC and NaCMC in retarding drug release rate was greater in distilled water than in dissolution media of pH 1 and 7.2. Cross-sectional view of the scanning electron micrograph showed that all of the coated spheroids exhibited a well-fused, continuous, and distinct layer of coating film. The drug release kinetics followed a biexponential first-order kinetic model.

The incidence of IDDM in Singapore children.

OBJECTIVE: To determine the incidence of insulin dependent diabetes mellitus (IDDM) in children 0-12 years of age in Singapore, which has a population of 2.9 million. METHODS: The primary source was a 2-year phone and mail survey of doctors in the government and government restructured hospitals and the private sector. The secondary source was the membership records of the Diabetes Society of Singapore. RESULTS: Using the capture-recapture method, ascertainment was assessed to be 92.2% complete. The age standardised incidence rate was 2.46 per 100,000 children 0-12 years old, for the period 1992-1994 (95% confidence interval: 2.16-2.75). The data seemed to indicate a rising incidence of IDDM in this population, being 1.4/100,000 in 1992, 2.4/100,000 in 1993 and 3.8/100,000 in 1994. The male: female ratio is 1:1.85. There was seasonal variation with fewer cases from July to October and more from November to May. Five percent of patients had a first degree relative with IDDM. Malays appeared to have a lower incidence (1.23/100,000) compared to the Chinese (2.25/100,000) and the Indians (5.78/100,000). CONCLUSIONS: The incidence of IDDM in Singapore children is similar to that reported for Hong Kong and Japan, but higher than that for Shanghai. The female preponderance is similar to that seen in other Asian population. The data suggests a rising incidence of IDDM in Singapore and differences in incidence between the Malays, Chinese and Indians, but further observations are needed.