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Background: Pretreatment with topical imiquimod, a synthetic agonist of toll-like receptor 7, significantly improved the immunogenicity of influenza vaccination in elderly people. We aimed to clarify its effect in a younger age group., Methods: In this double-blind, randomised controlled trial, we enrolled healthy volunteers aged 18-30 years in early 2014 to receive the 2013-14 northern-hemisphere winter trivalent influenza vaccine at the Queen Mary Hospital, (Hong Kong, China). Eligible participants were randomly assigned (1:1:1:1) to one of the four vaccination groups: the study group, topical imiquimod-cream followed by intradermal trivalent influenza vaccine (INF-Q-ID), or one of three control groups, topical aqueous-cream control followed by intradermal trivalent influenza vaccine (INF-C-ID), topical aqueous-cream control followed by intramuscular trivalent influenza vaccine (INF-C-IM), and topical imiquimod-cream followed by intradermal normal-saline injection (SAL-Q-ID). Randomisation was by computer-generated lists in blocks of four. The type of topical treatment was masked from volunteers and investigators, although not from the study nurse. Serum haemagglutination-inhibition and microneutralisation-antibody titres were assayed. The primary outcome was seroconversion at day 7 after treatment for three vaccine strains of influenza (A/California/07/2009 H1N1-like virus [A/California/H1N1], A/Victoria/361/2011 H3N2-like virus [A/Victoria/H3N2], and B/Massachusetts/2/2012-like virus [B/Yamagata lineage]) and four non-vaccine strains (A/HK/485197/14 [H3N2 Switzerland-like lineage], prototype A/WSN/1933 [H1N1], A/HK/408027/09 [prepandemic seasonal H1N1], and B/HK/418078/11 [Victoria lineage]). Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT02103023., Findings: We enrolled 160 healthy volunteers between March 1 and May 31, 2014, and 40 participants were randomly assigned to each study group. For the A/California/H1N1 strain, seroconversion at day 7 occurred in 39 participants (98%) in the INF-Q-ID group, 25 (63%) in the INF-C-ID group, 18 (45%) in the INF-C-IM group, and none in the SAL-Q-ID group; for the A/Victoria/H3N2, this was 30 (75%) in the INF-Q-ID group, four (10%) in the INF-C-ID group, four (10%) in the INF-C-IM group, and none in the SAL-Q-ID group; and for the B/Massachusetts (Yamagata lineage) strain, this was 36 (90%) in the INF-Q-ID group, 27 (68%) in the INF-C-ID group, 17 (43%) in the INF-C-IM group, and one (3%) in the SAL-Q-ID group (p<0·0001 for all three vaccine strains). Adverse reactions were infrequent and self-limited and did not differ between the four groups. Furthermore, the seroconversion rate against the four non-vaccine strains was better in the INF-Q-ID group than in the control groups on days 7 and 21 (p<0·0001). The most common adverse events were grade 1 redness (five participants in the INF-Q-ID group, three in INF-C-ID, one in INF-C-IM, and one in SAL-Q-ID) and grade 1 swelling (seven participants in INF-Q-ID group, five in INF-C-ID, three in INF-C-IM, and two in SAL-Q-ID., Interpretation: Topical application of imiquimod before intradermal trivalent influenza vaccine significantly improved immunogenicity against the vaccine influenza strains in young healthy individuals and increased immunogenicity against the non-vaccine strains, especially the antigenically drifted H3N2 strain of 2015, which was not included in the 2013-14 recommended vaccine. Further studies should be done to establish the efficacy and safety of this approach for other injectable vaccines to augment the onset and range of protection., Funding: The Shaw Foundation Hong Kong, Health and Medical Research Fund (Hong Kong, China), The Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Disease for the HKSAR (Department of Health, Hong Kong, China), The Providence Foundation, Respiratory Viral Research Foundation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Methylation of histone H4 on lysine 20 plays critical roles in chromatin structure and function via mono- (H4K20me1), di- (H4K20me2), and trimethyl (H4K20me3) derivatives. In previous analyses of histone methylation dynamics in mid-gestation mouse embryos, we documented marked changes in H4K20 methylation during cell differentiation. These changes were particularly robust during myogenesis, both in vivo and in cell culture, where we observed a transition from H4K20me1 to H4K20me3. To assess the significance of this change, we used a gain-of-function strategy involving the lysine methyltransferases SUV420H1 and SUV420H2, which catalyze H4K20me2 and H4K20me3. At the same time, we characterized a second isoform of SUV420H1 (designated SUV420H1&#95;i2) and compared the activity of all three SUV420H proteins with regard to localization and H4K20 methylation., Principal Findings: Immunofluorescence revealed that exogenous SUV420H1&#95;i2 was distributed throughout the cell, while a substantial portion of SUV420H1&#95;i1 and SUV420H2 displayed the expected association with constitutive heterochromatin. Moreover, SUV420H1&#95;i2 distribution was unaffected by co-expression of heterochromatin protein-1α, which increased the targeting of SUV420H1&#95;i1 and SUV420H2 to regions of pericentromeric heterochromatin. Consistent with their distributions, SUV420H1&#95;i2 caused an increase in H4K20me3 levels throughout the nucleus, whereas SUV420H1&#95;i1 and SUV420H2 facilitated an increase in pericentric H4K20me3. Striking differences continued when the SUV420H proteins were tested in the C2C12 myogenic model system. Specifically, although SUV420H1&#95;i2 induced precocious appearance of the differentiation marker Myogenin in the presence of mitogens, only SUV420H2 maintained a Myogenin-enriched population over the course of differentiation. Paradoxically, SUV420H1&#95;i1 could not be expressed in C2C12 cells, which suggests it is under post-transcriptional or post-translational control., Conclusions: These data indicate that SUV420H proteins differ substantially in their localization and activity. Importantly, SUV420H2 can induce a transition from H4K20me1 to H4K20me3 in regions of constitutive heterochromatin that is sufficient to enhance myogenic differentiation, suggesting it can act an as epigenetic 'switch' in this process.

Smoking is a major cardiovascular risk factor and cause of death. Diabetes mellitus is also associated with an increased mortality and morbidity. Evidence concerning whether smoking increases the incidence of diabetes remains conflicting. Glycaemic status and smoking habits were analysed in 3718 Chinese subjects in order to assess the possible association between smoking and risk of diabetes in the Chinese population. The World Health Organisation 1998 criteria were used for the diagnosis of glucose intolerance. Smoking was defined as current cigarette smoking or ex-smoking without regard to daily consumption. The smoking habits of the studied subjects were correlated with glycaemic status. There were 3003 (80.8%) women and 715 (19.2%) men. The mean age (SD) was 38.4 (12.8) years (median 35.0, range 12-88 years). Of the 3718 subjects, 786 (21.1%) had diabetes, 708 (19.1%) had impaired glucose tolerance, and 2224 (59.8%) had normal results. Of the 3003 women, only 87 (2.9%) were smokers. The female smokers were younger, heavier, and had higher alcohol consumption than non-smokers. The prevalence of diabetes was similar between female smokers and non-smokers after adjustment for age, body mass index, family history of diabetes, and alcohol. Of the 715 men, 175 (24.5%) were smokers. The male smokers were younger, had lower blood pressure, and higher alcohol consumption. After adjustment for age, body mass index, family history of diabetes and alcohol, the male smokers had lower blood pressure, higher one hour plasma glucose, and more diabetes. Using logistic regression analysis (stepwise forward) with age, body mass index, alcohol, smoking, and family history of diabetes as independent variables to predict the risk of having diabetes, age and body mass index are independently associated with diabetes in both men and women. In addition, smoking is independently associated with the risk of diabetes in men, the odds ratio (95% confidence interval, CI) being 1.705 (1.106 to 2.630). Family history of diabetes is independently associated with the risk of diabetes in women, and the odds ratio (95% CI) is 1.643 (1.314, to 2.053). In conclusion, it was found that smoking is independently associated with diabetes after adjustment for age, body mass index, alcohol, and family history of diabetes in Hong Kong Chinese men, the odds ratio being 1.7. The prevalence of smoking in Hong Kong Chinese women is low and its association with diabetes is inconclusive.

To examine whether a low socio-economic status (SES) is an additional risk factor for glucose intolerance in Hong Kong Chinese with known risk factors for glucose intolerance, a total of 2847 Chinese subjects (473 men and 2374 women) were recruited from the community for assessment. They had known risk factors for glucose intolerance including a previous history of gestational diabetes, positive family history of diabetes in first degree relatives and equivocal fasting plasma glucose concentrations between 7 and 8 mmol/l or random plasma glucose concentrations between 8 and 11 mmol/l. The 2847 subjects were classified according to their education levels and occupations: education group 1 = high school or university, group 2 = middle school, group 3 = illiterate or up to elementary school; occupational group 1 = professional or managerial, group 2 = non-manual, group 3 = manual, group 4 = unskilled, group 5 = housewife or unemployed. Different socio-economic groups were well represented in this selected population. The distribution of educational groups in this study was similar to that recorded in the 1991 Hong Kong Census. When analysed according to education levels and after adjustment for age, women in the lowest social class had the highest prevalence of diabetes, body mass index, blood pressure and plasma glucose concentrations. Men with the lowest education level had the highest prevalence of diabetes after age adjustment. The age-adjusted odds ratio (95% confidence intervals) of having diabetes was 2.3 (1.3. 4.3) in female subjects and 2.5 (1.2, 5.4) in male subjects with the lowest SES compared to subjects with the highest SES. When categorised according to occupation and after adjustment for age, women in the lowest social class had the highest prevalence of diabetes and glycaemic indexes. The age-adjusted odds ratio of having diabetes was 4.5 (1.9, 10.9) in female subjects with the lowest SES compared to those with the highest SES. The corresponding age-adjusted odds ratio in male subjects was 1.9 (0.9, 3.9) but this was not statistically significant. In conclusion, a lower socio-economic class, categorised either by occupational or educational level, was an additional risk factor for diabetes in Hong Kong Chinese who had known risk factors for glucose intolerance. These subjects should have increased priority for health education and regular diabetes screening. Our findings further emphasise the complex relationships between societal affluence, personal income and educational level.

Objective: We have previously suggested using the paired values of fasting plasma glucose (FPG) and HbA1c to identify potential diabetic subjects. In this article, we followed up on 208 nondiabetic subjects and examined their rates of progression to diabetes. We analyzed their likelihood of becoming diabetic according to their baseline FPG and HbA1c concentrations., Research Design and Methods: Between 1988 and 1995, 2,877 Chinese subjects with risk factors for diabetes underwent screening. Of these, 2,250 had FPG <7.8 mmol/l and 2-h plasma glucose (PG) <11.1 mmol/l. Of these 2,250 subjects, 265 were randomly recruited for an annual oral glucose tolerance test (OGTT) until they progressed to develop diabetes. Of those 265 subjects, 57 had baseline FPG > or =7.0 mmol/l and were excluded from the present analysis. Hence, the progression of glucose tolerance in 208 subjects who were nondiabetic according to the new American Diabetes Association diagnostic criteria (FPG < 7.0 mmol/l and 2-h PG < 11.1 mmol/l) was examined, Results: Of the 208 nondiabetic subjects, 26 (12.5%) were men and 182 (87.5%) were women. After a mean follow-up of 1.60 +/- 1.16 years (range 1-7, median 1), 44 (21.2%) progressed to develop diabetes and 164 (78.8%) remained nondiabetic. Those who were diabetic at the end of the study had a high likelihood ratio (LR) of 9.3 to have baseline FPG > or =6.1 mmol/l and baseline HbA1c > or =6.1%. This was compared with a low LR of 0.6-1.1 in diabetic subjects who had either FPG <6.1 mmol/l or HbA1c <6.1% or both at baseline. The crude rate of progression to diabetes was more than five times higher (44.1 vs. 8.1%) in those whose baseline FPG was > or =6.1 mmol/l and baseline HbA1c was > or =6.1% compared with those whose baseline FPG was <6.1 mmol/l and baseline HbA1c was <6.1%., Conclusions: For Chinese subjects with risk factors for glucose intolerance, the use of paired FPG and HbA1c values helped to identify potential diabetic subjects. Those with an FPG > or =6.1 mmol/l and HbA1c > or =6.1% had a rate of progression to diabetes more than five times higher than those with an FPG <6.1 mmol/l and an HbA1c <6.1% after a mean follow-up of 1.6 years. Those with an FPG > or =6.1 but <7.0 mmol/l, especially if their HbA1c was > or =6.1%, should undergo an OGTT to confirm diabetes. Subjects with an FPG <6.1 mmol/l and/or an HbA1c <6.1% should have regular screening using the paired values of FPG and HbA1c.

Objective: To examine the significance of individual risk factors on the development of diabetes in subjects who underwent screening for diabetes., Research Design and Methods: A total of 1,649 Chinese subjects underwent screening for diabetes. They were asymptomatic but had known risk factors for diabetes, including a positive family history of diabetes, a past history of gestational diabetes, obesity, hypertension, and/or dyslipidemia. Another 799 age-matched subjects from the community who had no risk factors for diabetes were used as the comparison group., Results: Of the 1,649 subjects who underwent screening, 241 (14.6%) had diabetes. In these subjects, 989 (60.0%) had 1 risk factor, 502 (30.4%) had 2 risk factors, 141 (8.6%) had 3 risk factors, and 17 (1.0%) had 4 or 5 risk factors for diabetes. Of the 799 control subjects, 29 (3.6%) had diabetes. Compared with the comparison group, the odds ratio (95% CI) of having diabetes after adjustment for age was 5.2 (3.5-7.7) in the 1,649 subjects with known risk factors. The odds ratio of having diabetes increased from 3.7 in subjects with 1 risk factor to 28.4 in subjects with 4 or 5 risk factors., Conclusions: In men, age, BMI, family history of diabetes, and dyslipidemia, and in women, age, BMI, hypertension, dyslipidemia, total cholesterol, and history of gestational diabetes are associated with increased odds of developing diabetes. These risk factors have additive effects on the odds of having diabetes. Early and regular screening for diabetes and other cardiovascular risk factors is essential in these high-risk individuals.

Women with a history of gestational diabetes (GDM) are at increased risk of developing diabetes compared with other women. There are few data on associations between GDM and cardiovascular risk factors. Between 1988 and 1995, 801 Chinese women with a history of GDM were recruited for a 75g oral glucose tolerance test (OGTT) and assessment of various cardiovascular risk factors, namely obesity, hypertension and dyslipidaemia, 6 weeks after delivery at the Diabetes Centre of the Prince of Wales Hospital. Another 431 women with no past history of diabetes or GDM recruited in a diabetes prevalence study were used as control subjects. After adjustment for age, body mass index and smoking, the prevalence of glucose intolerance remained higher in women with a history of GDM when compared to normal controls. The relative risks of obesity, hypertension, dyslipidaemia, diabetes and impaired glucose tolerance in women with a history of GDM comparing to normal subjects were, respectively, 2.4, 7.5, 2.4, 8.1 and 5.0. After excluding those with abnormal glucose tolerance, subjects with a history of GDM still had more adverse cardiovascular risk factors, including higher blood pressure, glycaemic and lipid parameters, than control subjects (after adjustment for age, body mass index and smoking). In conclusion, compared with normal subjects, Chinese women with a history of GDM had an 8-fold increased risk of having diabetes based on their OGTTs performed 6 weeks postdelivery. These women also have increased rates of other cardiovascular risk factors including obesity, high blood pressure and dyslipidaemia.

Aims: To examine and compare gastrointestinal (GI) symptoms in Hong Kong Chinese Type 2 diabetic outpatients and non-diabetic control subjects., Methods: A total of 149 Chinese Type 2 diabetic patients (66 men and 83 women, age (mean +/- SD) 46.8+/-11.1 years) newly referred to the diabetes clinic of the Prince of Wales Hospital, Hong Kong were examined. Sixty-five age and sex-matched non-diabetic subjects were recruited from the community as controls (22 men and 43 women, age (mean +/- SD) 46.5+/-6.6 years, P = 0.820). All patients were interviewed regarding GI symptoms over the past year, using a questionnaire that covered 14 items. A scoring system from 0 to 4 was used to grade severity., Results: Diabetic patients had higher blood pressure, fasting plasma glucose and glycated haemoglobin and were more often smokers than control subjects. Of the 149 diabetic subjects, 105 (70.5+/-45.8%) had GI symptoms while only 20 (30.8%) of the 65 control subjects had GI symptoms (P<0.001). The respective percentages of upper and lower GI symptoms in diabetic and normal subjects were 44.3% vs. 24.6% (P = 0.006) and 54.4% vs. 13.9% (P<0.001). The three commonest GI symptoms in diabetic patients were diarrhoea (34.9%), constipation (27.5%) and epigastric fullness (16.8%). After adjustment for age, sex, duration of diagnosed diabetes and smoking, patients with or without metformin had similar percentages or scores for GI symptoms. On multivariate analysis using age, body mass index, fasting plasma glucose, glycated haemoglobin, duration of diagnosed diabetes and presence of peripheral neuropathy as independent variables, duration of diabetes was the only independent parameter associated with total score for GI symptoms (beta = 0.116, P = 0.003), for upper GI symptoms (beta = 0.073, P = 0.005) and for lower GI symptom (beta = 0.043, P = 0.020)., Conclusions: Up to 70% of the Chinese Type 2 diabetic outpatients have GI symptoms, which is a much higher rate than in non-diabetic control subjects. Duration of diabetes is the most important factor associated with the presence of such GI symptoms.

In type 2 diabetes, it is not uncommon to find an elevated serum triglyceride and/or reduced high-density lipoprotein (HDL) cholesterol levels; elevated total cholesterol levels often occur as well. To evaluate the short-term efficacy and tolerability of combination therapy with lovastatin and acipimox in Chinese patients with type 2 diabetes who have mixed dyslipidemia, an open-label 6-month trial was conducted. All patients had type 2 diabetes (n = 33) with total cholesterol > or = 6.2 mmol/L and fasting triglyceride > or = 2.8 mmol/L, which had been confirmed twice and persisted for at least 12 weeks after introduction of diet control. After a 4-week run-in period, they were given lovastatin 40 mg daily at night for 12 weeks. Acipimox 250 mg three times a day was then added for a further 12 weeks. After 12 weeks of treatment with lovastatin alone, improvement was observed in total cholesterol (21% reduction), triglyceride (32% reduction), low-density lipoprotein (LDL) cholesterol (5.5% reduction), HDL cholesterol (11.6% elevation), apolipoprotein A-I (4.6% elevation), and apolipoprotein B (20.5% reduction). The addition of acipimox to lovastatin for an additional 12 weeks further reduced serum total cholesterol, triglyceride, LDL cholesterol, and apolipoprotein B, but this additional decrease was not statistically significant. However, HDL cholesterol and apolipoprotein A-I levels were significantly increased by the addition of acipimox (a 14.2% and 9.0% elevation, respectively). Serum creatine phosphokinase increased slightly after 12 weeks of lovastatin but decreased to a concentration similar to baseline after 12 weeks of combination treatment. No patients reported muscle pain or weakness or other side effects. Combination treatment with lovastatin and acipimox appears to be a safe and effective therapy in patients with type 2 diabetes and mixed dyslipidemia, and has particular benefit in elevating serum HDL cholesterol and apolipoprotein A-I levels.

Objective: To assess the validity of using fasting plasma glucose (FPG) concentrations in conjunction with HbA1c or fructosamine for the screening of diabetes in high-risk individuals., Research Design and Methods: In this study 2,877 Hong Kong Chinese (565 [19.6%] men; 2,312 [80.4%] women) with various risk factors for glucose intolerance underwent a 75-g oral glucose tolerance test (OGTT) for screening of diabetes. The risk factors included a family history positive for diabetes, a history of gestational diabetes or impaired glucose tolerance, and obesity., Results: Using World Health Organization (WHO) criteria, 1,593 (55.4%) had normal glucose tolerance, 657 (22.8%) had impaired glucose tolerance, and 627 (21.8%) had diabetes. When the 1997 American Diabetes Association (ADA) criteria were applied, 394 (13.7%) had diabetes with an FPG > or = 7.0 mmol/l. Using multiple receiver operating characteristic curve analysis, the paired values of an FPG of 5.6 mmol/l and a HbA1c of 5.5% gave an optimal sensitivity of 83.8% and specificity of 83.6% to predict a 2-h plasma glucose (PG) > or = 11.1 mmol/l. Likewise, the paired values of an FPG of 5.4 mmol/l and a fructosamine level of 235 mumol/l (n = 2,408) gave an optimal sensitivity of 81.5% and specificity of 83.2%. An FPG > or = 5.6 mmol/l and an HbA1c > or = 5.5% was 5.4-fold more likely to occur in diabetic subjects (based on the WHO criteria) compared with nondiabetic subjects. For paired parameters less than these values, the likelihood ratio of this occurring in diabetic subjects was only 0.11. Similarly, an FPG > or = 5.4 mmol/l and a fructosamine > or = 235 mumol/l was fivefold more likely to occur in diabetic subjects than in nondiabetic subjects, with both parameters less than these values having a likelihood ratio of 0.04. Using these paired values as initial screening tests, only subjects who had an FPG > or = 5.6 mmol/l and < 7.8 mmol/l and an HbA1c > or = 5.5% (n = 642) required an OGTT to confirm diabetes, thereby saving 77.7% [(2,877-642)/2,877] of the OGTTs performed. Similarly, only subjects who had an FPG > or = 5.4 mmol/l and < 7.8 mmol/l and a fructosamine > or = 235 mumol/l (n = 526) required OGTT to confirm diabetes, meaning that 78.2% [(2,408-526)/2,408] of the OGTTs could have been saved. Based on the 1997 ADA criterion of an FPG cutoff value of 7.0 mmol/l, the corresponding numbers of OGTTs to be saved were 82.6% and 85.5%, respectively., Conclusions: The paired values of FPG and HbA1c or FPG and fructosamine helped to identify potentially diabetic subjects, the diagnosis of which could be further confirmed by the 75-g OGTT. Using this approach approximately 80% of OGTTs could have been saved, depending on the diagnostic cutoff value of FPG.

Objective: To investigate the safety, efficacy, and metabolic effects of dexfenfluramine in obese Chinese NIDDM patients., Research Design and Methods: Thirty-two patients, mean (+/- SD) body weight 76.2 +/- 8.5 kg with corresponding BMI 31.1 +/- 2.1 kg/m2, were randomized into a two-phase study, after a 2-week single-blind run-in period on placebo. Phase 1 was a randomized 3-month double-blind placebo-controlled trial during which either dexfenfluramine or placebo was added to the existing treatment regimens of diet plus or minus sulfonylureas without metformin. Phase 2 was a further 3-month single-blind trial during which the placebo group was given dexfenfluramine without patients' knowledge of changing to active medication, while the active group continued with dexfenfluramine. Body weight, glycemic control, blood pressure, lipids, and quality of life were assessed before and at 3 and 6 months after randomization. A total of 27 patients were also followed for an additional period of 6-12 months (215 +/- 53 days) after dexfenfluramine treatment was withdrawn., Results: During the run-in period, both groups were comparable for all parameters measured. At 3 months, mean changes in BMI were -1.2 +/- 1.0 kg/m2 (dexfenfluramine) vs. -0.1 +/- 0.5 kg/m2 (placebo) (P < 0.001). The mean changes in fasting plasma glucose were -1.14 +/- 0.99 vs. 0.51 +/- 1.34 mmol/l (dexfenfluramine vs. placebo, P = 0.004). HbA(1c) also significantly improved in the dexfenfluramine group (-0.80 +/- 0.53 vs. 0.25 +/- 0.64%, P < 0.001). During the 3-month single-blind dexfenfluramine treatment in the ex-placebo group, there were similar improvements in body weight and glycemic indexes. After cessation of dexfenfluramine therapy at 6 months, significant increases in body weight and glycemic indexes, almost back to the baseline, were observed for both groups., Conclusions: Dexfenfluramine aids weight loss and improves glycemic control in obese Chinese NIDDM patients over a 3- to 6-month period. These effects are emphasized after withdrawal of treatment and further support the longer-term use of dexfenfluramine for chronic complicated obesity.

Plasma fibrinogen concentration has been shown to be a predictor of major cardiovascular events. Information on plasma fibrinogen amongst Chinese has been scanty. We examined the relationships between plasma fibrinogen concentration and cardiovascular risk factors in 988 chinese subjects who underwent 75 g oral glucose tolerance test for screening for glucose intolerance. The study involved a selected sample with subjects who had an history of gestational diabetes, delivery of big babies (birth weight > or = 4 kg), equivocal plasma glucose concentrations and subjects who were family members of diabetic patients. This was mainly a non-smoking (96.6%), non-drinking (98%) and non-exercising (99%) population of which 87% (n = 855) were female. Among the 988 subjects (age +/- S.D. 36.8 +/- 10.2, range 16-79 years), plasma fibrinogen concentration ranged from 1.40 to 9.90 g/l with a mean of 3.26 +/- 0.93 g/l. On stratification of the subjects into 4 quartiles based on plasma fibrinogen concentrations, we found that increased plasma fibrinogen was associated with older age, higher body mass index (BMI), systolic and diastolic blood pressure (BP), fasting and 2 h plasma glucose (PG), prevalence of diabetes, glycated haemoglobin (HbA1c) and triglyceride (TG) level. After adjustment for age and sex, increased plasma fibrinogen concentration remained associated with higher BMI, systolic BP, 2 h PG and TG level. On multivariate analysis using age, BMI, BP, TG, HbA1c and PG as independent variables, plasma fibrinogen was independently related to plasma TG concentration and HbA1c. With 1 S.D. change in TG concentration and HbA1c, there were 3.7 and 5.2% changes in plasma fibrinogen concentration respectively. These findings emphasize the close relationships between plasma fibrinogen and cardiovascular risk factors, in particular abnormal lipid and glucose metabolism.

Objectives: Optimal insulin regimens for non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure are controversial. We evaluated the efficacy, side effects, and quality of life of patients receiving insulin either alone or in combination with their previous oral hypoglycemic agents (OHAs)., Research Design and Methods: Fifty-three Chinese patients with NIDDM (mean age 53.9 +/- 12.6 years, duration of diabetes 9.0 +/- 4.9 years, body wt 60.4 +/- 13.3 kg with corresponding body mass index 24.2 +/- 4.3 kg/m2, receiving the maximum dose of sulfonylurea and/or metformin) were confirmed to have OHA failure. Twenty-seven patients were randomized to continue OHAs and were given additional bedtime insulin (combination group); 26 patients were randomized to insulin therapy alone with twice-daily insulin (insulin group). Insulin doses were increased incrementally, aiming at fasting plasma glucose (FPG) < 7.8 mmol/l during a stabilization period of up to 8 weeks. Insulin dosage, body weight, glycemic control, and quality of life were assessed before and at 3 and 6 months after stabilization., Results: Both groups showed similar improvement of glycemic control. For the combination group, FPG decreased from 13.5 +/- 2.7 to 8.9 +/- 3.0 mmol/l at 3 months (P < 0.0001) and to 8.6 +/- 2.5 mmol/l at 6 months (P < 0.0001). For the insulin group, FPG decreased from 13.5 +/- 3.6 to 7.5 +/-3.0 mmol/l at 3 months (P < 0.0001) and to 9.8 +/- 3.5 mmol/l at 6 months (P < 0.0001). No significant differences were observed between the groups. Similarly, both groups had significant improvement of fructosamine and glycosylated hemoglobin (HbA1c). Fructosamine fell from a mean of 458 to 365 mumol/l at 3 months (P < 0.0001) and to 371 mumol/l at 6 months (P < 0.0001) and from 484 to 325 mumol/l at 3 months (P < 0.0001) and to 350 mumol/l at 6 months (P < 0.0001) for the combination and insulin groups, respectively. HbA1c decreased from 10.2 to 8.4% at 3 months (P < 0.0001) and to 8.7% at 6 months (P < 0.0001) in the combination group and from 10.7 to 7.8% at 3 months (P < 0.0001) and to 8.4% at 6 months (P < 0.0001) in the insulin group. Despite similar improvement of glycemia, insulin requirements were very different. At 3 months, the combination group was receiving a mean of 14.4 U/day compared with 57.5 U/day in the insulin group (P < 0.0001). Similar findings were observed at 6 months (15.0 vs 57.2 U/day, P < 0>0001). Both groups gained weight. However, for the combination group, weight gain was 1.6 +/- 1.8 kg at 3 months and 2.1 +/- 2.5% kg at 6 months (both P < 0.0001 vs baseline), whereas for the insulin group, weight gain was 3.5 +/- 4.3 and 5.2 +/- 4.1 kg, respectively (both P < 0.0001 vs baseline). Weight gain was significantly greater in the insulin group (P < 0.05 at 3 months, and P < 0.005 at 6 months). Fasting plasma triglyceride decreased in the insulin group (1.8 +/- 1.0 to 1.4 +/- 0.8 mmol/l at 3 months [P < 0.005] and to 1.4 +/ 0.7 mmol/l at 6 months [P < 0.02] but not in the combination group. No changes were observed in total and high-density lipoprotein cholesterol. No severe hypoglycemic reactions were recorded in either group. Mild reactions occurred with similar frequency in both groups. Well-being and quality of life improved significantly in both groups. The majority of patients (82.7%) wanted to continue insulin beyond 6 months, irrespective of the treatment group., Conclusions: In NIDDM patients with secondary OHA failure, therapy with a combination of OHAs and insulin and with insulin alone was equally effective and well tolerated. However, combination therapy was associated with a lower insulin dose and less weight gain. Combination treatment may be considered when OHA failure occurs as a potential intermediate stage before full insulin replacement.

An endonuclease activity has been purified from human adenovirus type 5 (HAd5) virions and HAd5-infected cell extracts. The endonuclease activity is associated with a monomeric protein of molecular weight approximately 33 000. The endonuclease activity is more active at pH 4.5 than pH 7.2. Incubation of the enzyme at room temperature for periods of longer than 96 h results in a substantial increase in activity. The endonuclease activity is sensitive to EDTA at concentrations 10mM or greater but is insensitive to 500 mM NaCl. Immunological analysis with endonuclease-specific antiserum indicates that the endonuclease may be a host cell derived, viral modified, and incorporated protein.

A measles virus (Halle SSPE isolate) induced ring plaque phenomenon (concentric rings of living and dead cells) has been shown to be associated with the temperature-dependent production of interfering particles. The interfering particles have been purified by potassium tartrate linear gradient centrifugation and have buoyant densities of 1.15 g/ml (M particle) and 1.06 g/ml (L particle) respectively. Both interfering particle population have been shown to decrease the yield of wild-type measles virus from infected cells by 50% when co-infection experiments were performed. Neither the M or L particle population interfered with the growth of VSV in the same host-cell system.