Implication of fibrate therapy for homocysteine.
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Diabetes Mellitus, Type 2↗
Biomedical subjects
J C Chan
Publications and source records attributed to J C Chan.
Age, body mass index and 2-hour plasma glucose are the major determinants of blood pressure in Chinese women newly diagnosed to have glucose intolerance.
Hypertension and diabetes frequently coexist and greatly increase cardiovascular risk. There are relatively few data on the relationship between blood pressure and plasma glucose in newly diagnosed diabetic subjects especially in Chinese. We examined the glycaemic status, blood pressure profiles and other clinical and biochemical characteristics in 1298 Hong Kong Chinese women. These women were referred to the Diabetes and Endocrine Center of the Prince of Wales Hospital for screening of diabetes. The reasons for referral included a positive family history of diabetes or a history of gestational diabetes. Of the 1298 subjects, 836 (64.4%) had normal oral glucose tolerance test, 284 (21.9%) had impaired glucose tolerance and 178 (13.7%) had diabetes. Compared to non-diabetic subjects, the odds ratio (95% confidence interval) of having hypertension in subjects with impaired glucose tolerance or diabetes were 2.83 (1.90, 4.23) (P<0.001) and 5.94 (3.94, 8.96) (P<0.001), respectively. When analyzed as a continuous variable by age-adjusted partial correlation coefficients, systolic blood pressure was correlated with body mass index, fasting and 2-h plasma glucose, while diastolic blood pressure was correlated with body mass index. Using age, body mass index, fasting and 2-h plasma glucose, glycated hemoglobin, cholesterol, triglyceride and smoking as independent variables in multivariate analysis, hypertension was independently related to age, body mass index and 2-h plasma glucose. In conclusion, increased blood pressure was common in Hong Kong Chinese women who were newly diagnosed to have glucose intolerance. Apart from age and body mass index, plasma glucose was an independent determinant for blood pressure in these subjects.
Adolescent↗
High-resolution heteronuclear correlation between quadrupolar nuclei.
Multiple-quantum magic angle spinning is successfully incorporated with double-quantum cross-polarization between quadrupolar nuclei, producing a two-dimensional 11B[27Al] high-resolution heteronuclear correlation spectrum for a magnesium aluminoborate glass. It is shown that the six-coordinate aluminum site (AlO6) preferentially coordinates to the tetrahedral boron site (BO4).
Magnetic Resonance Spectroscopy↗
Influence of alpha-tocopherol over the time course of experimental IgA nephropathy.
The present study investigated the pathogenesis and the time course of kidney injury in experimental IgA nephropathy. In order to determine an appropriate period in the course of experimental IgA nephropathy to study renal injury and repair, we examined proteinuria and IgA deposition in the renal mesangium after 4, 8, and 16 weeks of mucosal challenge by bovine gamma globulins (BGG) provided in the drinking water. The hallmark of IgA deposition in the mesangium was present after 4 weeks and 8 weeks of BGG inoculation, but by 16 weeks, the mesangial IgA deposition had resolved. In addition, we confirmed our previous report on the beneficial effects of alpha-tocopherol in reducing proteinuria in IgA nephropathy at 8 weeks, and extended this observation to investigate the effects of dietary supplementation of alpha-tocopherol at both 4 weeks and 16 weeks. Proteinuria resolved spontaneously at 16 weeks. There is oxidative stress, as suggested by the elevation in plasma and renal malondialdehyde content, and increased fibrogenic cytokine message, as suggested by elevated transforming growth factor beta1 mRNA. These increases were clearly blunted by alpha-tocopherol at both 4 weeks and 8 weeks. Treatment with alpha-tocopherol was associated with a significant reduction in the severity of proteinuria. Thus, our data suggest that the period between 4 and 8 weeks of BGG vaccination could be relevant in designing an appropriate model to study the molecular biology of the pathogenesis of renal injury and the effects of treatment. The 16-week model may be useful in exploring gene expression involved with spontaneous resolution.
Animals↗
Vitamin E suppresses oxidative stress and glomerulosclerosis in rat remnant kidney.
Previous studies have shown that reduction of renal mass in the rat remnant kidney model induces overproduction of transforming growth factor beta1 (TGFbeta1). We investigated whether an antioxidant, vitamin E, administered before the renal mass reduction, could prevent oxidative stress, reduce the overproduction of TGFbeta1, and mitigate against the subsequent glomerulosclerosis. Our results revealed that the oxidative stress, as measured by the change in plasma malondialdehyde, is significantly reduced by prior vitamin E dietary supplementation. Finally, our data show that dietary vitamin E supplementation ameliorates the rise in TGFbeta1 secondary to renal mass reduction and inhibits the glomerular sclerosis of the remnant kidney over the time course of this experiment.
Animals↗
The role of trisomy 8 in the pathogenesis of chronic eosinophilic leukemia.
A case of chronic eosinophilic leukemia (CEL) manifesting as spinal cord compression by an extradural eosinophilic chloroma in a 32-year-old Chinese man was presented, who subsequently developed extramedullary transformation at the skin and then peritoneal cavity. Cytogenetic study of bone marrow cells at diagnosis showed a clonal karyotypic abnormality of trisomy 8 (+8), which on fluorescence in situ hybridization (FISH) was shown to be present in a clone of abnormal eosinophils, hence showing the neoplastic nature of the eosinophilic proliferation. There was another population of abnormal eosinophils that did not show +8. At blastic transformation, all blast cells in ascitic fluid were shown by FISH to harbor +8. These findings suggest that +8 in this case may have arisen from clonal evolution and is not the primary genetic event in leukemogenesis, but +8 most probably imparts a further survival advantage to the clone responsible for subsequent blastic transformation.
Adult↗
Trisomy 21 as the sole acquired karyotypic abnormality in acute myeloid leukemia and myelodysplastic syndrome.
We report five cases of myeloid disorders in which trisomy 21 (+21) was found as the sole acquired karyotypic abnormality, comprising two cases of acute myeloid leukemia (AML) and three cases of myelodysplastic syndrome (MDS). In this series, MDS patients with +21 presented as high grade disease, which included two cases of refractory anemia with excess of blasts (RAEB) and one case of refractory anemia with excess of blasts in transformation (RAEBt), and showed rapid disease progression. Significant thrombocytopenia was observed in all three patients, and bone marrow examination showed a marked reduction in megakaryocytes. AML patients with +21 included one case each of AML-M2 and M4. Despite the poor prognosis reported in AML patients with +21 as the sole abnormality, the patient in our series who was able to complete intensive treatment was cured of disease. The role of +21 in leukemogenesis is reviewed.
Acute Disease↗
Clinical and biochemical characteristics of type 2 diabetic patients on continuous ambulatory peritoneal dialysis: relationships with insulin requirement.
Although glycemic control has an important impact on the clinical outcomes of patients with diabetes undergoing dialysis, there is a paucity of data on the relationship between glucose metabolism and clinical parameters in these patients. In this study, we compared a cohort of 48 patients with type II diabetes undergoing continuous ambulatory peritoneal dialysis (CAPD) with 84 age- and sex-matched patients with type II diabetes with similar disease duration but normal renal function. Compared with those with normal renal function, patients with type 2 diabetes undergoing CAPD had greater serum angiotensin-converting enzyme activity (median, 57.4 U/L; range, 33.5 to 100.0 U/L v 46.9 U/L; range, 11.6 to 111.2 U/L; P < 0.005), fasting C-peptide (median, 9.1 ng/mL; range, 0.9 to 30.0 ng/mL v 2.2 ng/mL; range, 0.2 to 20.3 ng/mL; P < 0.0001) and triglyceride levels, and lower serum albumin concentrations. Among the patients undergoing CAPD, there was a preponderance of men in the insulin-treated group. Insulin-treated patients also had greater plasma albumin levels and body weights and lower fasting serum C-peptide levels (2.81 +/- 1.77 v 3.12 +/- 2.04 ng/mL; analysis of variance, P = 0.007 adjusted for fasting glucose concentration). Multivariate analysis showed duration of diabetes, hemoglobin A(1c) (HbA(1c)) level, and body weight were independent determinants of insulin requirement in patients undergoing CAPD. The daily insulin dosage required was related to the duration of diabetes (r = 0.5; P = 0.007). In summary, among patients with end-stage renal failure, insulin-treated patients had greater body weights and plasma albumin levels but lower cholesterol levels. Plasma C-peptide concentration and duration of diabetes were the main determinants of insulin requirement, reflecting a decrease in beta-cell reserve, whereas the daily insulin dose correlated mainly with body weight, HbA(1c) level, and duration of diabetes. Kt/V had no effect on insulin resistance or insulin requirement of the patients.
Adult↗
Lack of association of angiotensin-converting enzyme (DD/II) and angiotensinogen M235T gene polymorphism with renal function among Chinese patients with type II diabetes.
The prevalence of diabetic nephropathy is greater in nonwhite patients with type II diabetes, including the Chinese, and genetic variation appears to have a role. We examined angiotensin-converting enzyme (ACE) DD/II and angiotensinogen (Atg) M235T polymorphism in a cohort of Chinese patients with type II diabetes with an average duration of diabetes of 14 years. Group A (n = 88) did not have significant diabetic nephropathy (creatinine levels </= 130 micromol/L [</=1.48 mg/L], without macroalbuminuria), and group B (n = 80) had significant diabetic nephropathy (macroalbuminuria or creatinine level >130 micromol/L [>1.48 mg/d], and those undergoing dialysis). The two groups were matched in different aspects, including age, duration of diabetes, blood pressure, and glycemic control. The results showed: (1) no difference of genotype distribution between groups A and B (DD:DI:II, 14%:45%:41% v 8%:38%:54%; P = 0.20; TT:TM/MM, 70%:30% v 76%:24%; P = 0.43), (2) no evidence of synergistic effect of ACE (DD/II) and Atg M235T gene polymorphisms, (3) no difference of allele frequencies between groups A and B (D:I, 36%:64% v 27%:73%; P = 0.20 and T:M, 86%:16% v 86%:14%; P = 0.73), and (4) ACE activity was greatest in patients with DD genotype and least in those with II genotype (DD:DI:II = 66. 9 +/- 13.3 U/L:61.5 +/- 19.9 U/L:45.0 +/- 17.0 U/L; P < 0.005). The data do not support a role of ACE (DD/II) or Atg M235T polymorphism in the development of diabetic nephropathy in Chinese patients with type II diabetes, and no synergistic effect was found between them. Greater ACE activity was associated with DD genotype, and its role in diabetic nephropathy remains to be elucidated.
Aged↗
Negative captopril renography on patients with renin mediated hypertension due to page kidney and reninoma.
Through a mechanism similar to renal artery stenosis, patients with reninoma and page kidney also suffered from renin mediated hypertension. Captopril renograms performed on our patients with the latter two conditions, however, did not yield diagnostic findings. Therefore, equivocal or negative captopril renography cannot serve to rule out conditions with elevated renin other than renal artery stenosis.
Angiotensin-Converting Enzyme Inhibitors↗
Prediction of hypertension, diabetes, dyslipidaemia or albuminuria using simple anthropometric indexes in Hong Kong Chinese.
OBJECTIVE: It is important to determine what values of simple anthropometric measurements are associated with the presence of adverse cardiovascular risk factors such as diabetes or hypertension to provide an indication for further detailed investigations. In this analysis, we aimed to assess which anthropometric cutoff values are best at predicting the likelihood of diabetes, hypertension, dyslipidaemia and albuminuria in Hong Kong Chinese. DESIGN AND SETTING: The data were obtained from a previously reported prevalence survey for glucose intolerance in a representative Hong Kong Chinese working population. SUBJECTS: 1513 subjects (910 men and 603 women) with mean age+/-s.d. 37.5+/-9.2 y. MEASUREMENTS: We examined the likelihood ratios of having diabetes, hypertension, dyslipidaemia and albuminuria in subjects with various cutoff values of the four simple anthropometric indexes, namely, body mass index, waist-hip ratio, waist circumference and the ratio of waist-to-height. RESULTS: We developed a nomogram to show the predictive values of different indexes for the cardiovascular risk factors using likelihood ratio analysis. Using Caucasian mean levels of the simple anthropometric indexes to predict diabetes or hypertension in Hong Kong Chinese gave a high likelihood ratio of 2:3:5. CONCLUSION: Higher levels of body mass index, waist-hip ratio, waist circumference and the ratio of waist-to-height are associated with risk of having diabetes mellitus or hypertension in Hong Kong Chinese as in Caucasians. However, the cutoff values of those anthropometric indexes to define obesity used in Caucasians may not be applicable to Chinese.
Adult↗
Gastrointestinal symptoms in Chinese patients with Type 2 diabetes mellitus.
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.
Adult↗
Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor-1alpha genes in patients with early-onset type 2 diabetes mellitus/MODY.
AIMS: To examine the prevalence of identified MODY-related genes in Chinese subjects with early onset Type 2 diabetes mellitus and a positive family history of diabetes and to look for possible associations between the gene mutations and the development of diabetes. METHODS: Ninety-two unrelated Chinese subjects with diabetes diagnosed before the age of 40 years who had a positive family history of diabetes were screened for mutations in hepatocyte nuclear factors (HNF-1alpha and HNF-4alpha) and glucokinase genes by direct sequencing. The family members of patients with mutations and 100 healthy controls were also examined. RESULTS: Mutations in the HNF-1alpha and the glucokinase genes were found in 5% and 3% of the diabetic subjects, respectively but no mutations were found in the coding region of the HNF-4alpha gene. Three mutations found in the glucokinase gene were novel missense mutations (I110T, A119D and G385V). The mutations in the HNF-1alpha gene were also new and included four missense mutations (G20R, R203H, S432C, I618M) and one splice acceptor site mutation (IVS2nt-1G-->A). Patients with mutations in these genes were clinically heterogeneous with respect to phenotype and basal pancreatic beta cell function. CONCLUSIONS: Genetic factors such as mutations in the HNF-1alpha and glucokinase genes may be important in the development of diabetes in Chinese people, especially when the disease is of early onset.
Adolescent↗
Combating bacterial resistance in skin and skin-structure infection: importance of beta-lactamase inhibition.
Serious skin and skin-structure infections may require parenteral antibiotic therapy. Such infections are generally polymicrobial, and they often involve both gram-positive and gram-negative aerobes as well as anaerobic bacteria. Effective treatment thus requires the use of a broad-spectrum antibiotic or combination therapy. The development of antibiotic resistance by clinically important pathogens has significantly increased the difficulty of treating skin and skin-structure infections. One of the major mechanisms of resistance observed in organisms likely to be associated with such infections is the development of beta-lactamases that inactivate beta-lactam antibiotics. Two approaches have been taken to combat this problem: the use of beta-lactam/beta-lactamase inhibitor combinations and the development of beta-lactamase-stable drugs. Both strategies have resulted in treatments that are clinically and bacteriologically effective in patients with skin and skin-structure infections. The use of one beta-lactam/beta-lactamase inhibitor combination, ampicillin/sulbactam, has been demonstrated to be more cost-effective than treatment with beta-lactamase-stable antibiotics, such as cefoxitin and imipenem/cilastatin, for this indication.
Anti-Bacterial Agents↗
Glucose intolerance and other cardiovascular risk factors in chinese women with a history of gestational diabetes mellitus.
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.
Adolescent↗
Factor VII deficiency rescues the intrauterine lethality in mice associated with a tissue factor pathway inhibitor deficit.
Mice doubly heterozygous for a modified tissue factor pathway inhibitor (TFPI) allele (tfpi delta) lacking its Kunitz-type domain-1 (TFPI+/delta) and for a deficiency of the factor VII gene (FVII+/-) were mated to generate 309 postnatal and 205 embryonic day 17.5 (E17. 5) offspring having all the predicted genotypic combinations. Progeny singly homozygous for the tfpidelta modification but with the wild-type fVII allele (FVII+/+/TFPIdelta/delta), and mice singly homozygous for the fVII deficiency and possessing the wild-type tfpi allele (FVII-/-/TFPI+/+), displayed previously detailed phenotypes (i.e., a high percentage of early embryonic lethality at E9.5 or normal development with severe perinatal bleeding, respectively). Surprisingly, mice of the combined FVII-/-/TFPIdelta/delta genotype were born at the expected mendelian frequency but suffered the fatal perinatal bleeding associated with the FVII-/- genotype. Mice carrying the FVII+/-/TFPIdelta/delta genotype were also rescued from the lethality associated with the FVII+/+/TFPIdelta/delta genotype but succumbed to perinatal consumptive coagulopathy. Thus, the rescue of TFPIdelta/delta embryos, either by an accompanying homozygous or heterozygous FVII deficiency, suggests that diminishment of FVII activity precludes the need for TFPI-mediated inhibition of the FVIIa/tissue factor coagulation pathway during embryogenesis. Furthermore, the phenotypes of these combined deficiency states suggest that embryonic FVII is produced in mice as early as E9.5 and that any level of maternal FVII in early-stage embryos is insufficient to cause a coagulopathy in TFPIdelta/delta mice.
Animals↗
Effect of the synthetic glucocorticoid, deflazacort, on body growth, pulsatile secretion of GH and thymolysis in the rat.
DESIGN: Deflazacort (DFZ) is a relatively new glucocorticoid that has been reported to exhibit fewer side-effects than other commonly used corticosteroids. The present study was designed to test the effects of DFZ on thymus gland involution (thymolysis), as compared with body growth and the secretory pattern of GH in the rat. Beginning at 38 days of age, male animals were treated for 8 consecutive days by s.c. injection of DFZ (0.15mg/day), cortisone (CORT) (5mg/day) or vehicle (control, CTRL). RESULTS: Both glucocorticoids had a similar thymolytic effect and caused growth failure, but the growth rate for the DFZ group was significantly higher than that of the CORT group. On day 46, pulsatile GH secretion was quantitated by blood sampling via an indwelling catheter at 10 min intervals for 6h. GH was assayed by RIA and analyzed by multiparameter deconvolution. CORT caused an increase in pulse frequency (5.8+/-0.4 (s.e.m.)) in comparison to DFZ (4.4+/-0. 4) and CTRL (3.8+/-0.3). Both glucocorticoids significantly shortened the interval between secretory bursts. In CTRL animals the interval between bursts was 69.3+/-4.5 min. In DFZ animals this was reduced to 58.5+/-7.1 min, and in CORT rats it was further reduced to 47.0+/-2.6 min. The mass of GH secreted per burst was reduced in CORT animals (52% of CTRL), while DFZ did not alter this parameter. A similar trend was observed for total GH production, with CORT causing a reduction and DFZ not affecting the secretion. CONCLUSION: Rats treated with glucocorticoid show a profound thymolytic effect, as well as important changes in growth. While CORT suppresses GH secretion and alters its pulsatile mode of release, DFZ causes a less significant alteration in the pattern of GH secretion and does not negatively affect the overall amount of GH secreted.
Animals↗
Choledochal cyst and adult intestinal malrotation: a rare association.
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Adenocarcinoma↗