Adiponectin gene (ADIPOQ) polymorphisms correlate with the progression of nephropathy in Taiwanese male patients with type 2 diabetes

Aims

Polymorphisms of the ADIPOQ gene were associated with diabetic nephropathy (DN) in case–control studies predominantly among European populations. Gender may modify the ADIPOQ associated risk for DN. We investigated the association of 18 ADIPOQ polymorphisms with DN in a prospective Taiwanese cohort of type 2 diabetes (T2D) and explored whether gender plays a role in this genetic association.

Methods

Selected single nucleotide polymorphisms (SNPs) of ADIPOQ were genotyped in 566 T2D patients with normoalbuminuria at baseline. DN was defined based on urinary albumin-to-creatinine ratio (ACR). The Cox proportional hazard model was used to explore the association of individual SNP to DN events under different genetic models over a 6-year follow-up period. Analyses were further stratified by gender.

Results

In male patients, the adjusted hazard ratios under the recessive models were 1.81 for rs2241766 TT (vs. GT + GG, 95% CI = 1.10–2.96, p = 0.019) and 1.89 for rs1063537 CC (vs. CT + TT, 95% CI = 1.15–3.11, p = 0.013). In the Kaplan–Meier survival curve, males carrying rs2241766 TT (vs. GT + GG, p = 0.050) and rs1063537 CC (vs. CT + TT, p = 0.037) recessive homozygotes also had a reduced nephropathy-free survival rate. SNPs rs2241767 and rs2082940, both in strong correlation with tag SNP rs1063537 (r² ≥ 0.96), were also associated with DN progression in males. In females, ADIPOQ polymorphisms were not associated with the progression of DN.

Conclusions

ADIPOQ genetic polymorphisms rs2241766 (+45T>G), rs1063537, rs2241767 and rs2082940 were correlated with the progression of DN in Taiwanese male patients with T2D. The role of gender in this ADIPOQ genetic association needs to be further investigated in other populations.     

Blood use in patients undergoing repeat coronary artery bypass graft procedures: multivariate analysis

BACKGROUND : The prevailing clinical opinion is that patients undergoing repeat coronary artery bypass graft (CABG) operation require more blood transfusions than do patients undergoing primary CABG operation. To determine the extent of this increased demand and the variables responsible for it, the cases of 196 patients who had undergone primary procedures and 65 patients who had had repeat procedures at the same institution were reviewed. STUDY DESIGN AND METHODS : To analyze the differences in transfusion requirements for these two groups, the following data were obtained: number of transfusions given between the time of surgery and the time of hospital discharge; preoperative hemoglobin (Hb), hematocrit (Hct), prothrombin time, and platelet count; Hb and Hct at hospital discharge; time the patient was on cardiopulmonary bypass; number and type of grafts; estimates of intraoperative blood loss; and chest-tube blood shed during the first 48 hours after surgery. RESULTS : The groups were comparable with respect to age, body weight, preoperative Hb and Hct, number of grafts, and aspirin exposure. Patients in the repeat group had 35-percent greater blood loss and required 75-percent more blood components than did the patients undergoing primary procedures. The mean number of blood components transfused per patient was as follows: red cells, 3.8 +/? 0.5 units in repeat patients and 2.2 +/? 0.2 units in primary patients (p = 0.002); platelets, 2.9 +/? 0.9 vs. 1.1 +/? 0.2 (p = 0.043); fresh-frozen plasma, 1.6 +/? 0.4 vs. 0.8 +/? 0.1 (p = 0.044). Analysis of variables by regression method for repeat patients showed a predictive effect of blood loss (p < 0.0001), prolonged time on cardiopulmonary bypass (p < 0.0001), preoperative Hb (p = 0.0003), and aspirin exposure (p = 0.0094) on red cell transfusion rate in repeat patients (R-square = 0.7778, Prob > f = 0.0001). CONCLUSION : Repeat CABG patients have higher transfusion rates. These findings may be attributed to the increased microvascular bleeding, prolonged time on cardiopulmonary bypass, lower preoperative Hb, and the use of preoperative antiplatelet medications.     

Glycosylation and cold platelet storage

Platelets, unlike red blood cells and plasma, are stored at room temperature because platelets transfused after refrigeration at 4 degrees C are rapidly cleared from the circulation. Storage at room temperature promotes bacterial proliferation, however, and transfusion-transmitted bacteremia has become an increasing problem. Traditionally, the cold storage lesion has been attributed to a change in platelet shape from disc to sphere, but Hoffmeister et al. revisited this issue and have shown that the shape change induced by cold storage does not result in poor platelet survival. Instead, they showed that poor survival results from a virtually irreversible clustering of alpha subunits of glycoprotein Ib (GPIbalpha)) on the platelet surface. In a series of elegant papers, these researchers change the way we view platelet clearance. That is, they show that exposed, terminal, beta-linked N-acetylglucosamine (beta-GlcNAc) residues on clustered GPIbalpha are recognized by the lectin domain of type 3 complement receptors on liver macrophages, leading to rapid clearance by phagocytosis. They also demonstrate that phagocytosis of chilled platelets can be inhibited--and in vivo survival prolonged--by enzymatically galactosylating the terminal beta-GlcNAc residues on GPIbalpha. Disguising the exposed beta-GlcNAc residues on the N-glycans of the clustered GPIbalpha molecules by galactosylation is a promising approach to storing platelets at 4 degrees C without affecting platelet function. Cold storage would limit bacterial proliferation and extend the duration of platelet storage, reducing the incidence of transfusion-transmitted bacteremia and improving the availability of this scarce resource.     

波形蛋白、细胞角蛋白5,18,19在人胚胎前列腺发育不同阶段的表达及意义

目的 探讨波形蛋白（Vimentin），细胞角蛋白（Cytokeratin）5、18、19（CK5、18、19）在人胚胎前列腺发育不同阶段组织及细胞中的定位表达变化及其在前列腺胚胎发育中的意义。方法 应用免疫组织化学方法研究Vimentin、CK5、CK18、CK19在不同胎龄前列腺组织中的表达变化。结果 胚胎前列腺上皮细胞中波形蛋白随胎龄增大其表达呈由弱到强，又由强减弱的变化趋势；CK5和CK18的表达起初分布无规律，但是随胎龄增大，CK5和CK18逐渐分别定位表达于基底细胞层和管腔上皮细胞层；CK19则在基底细胞层和管腔上皮细胞层中均有表达，且强度较一致，基本不随胎龄增大而变化。结论 胚胎前列腺上皮细胞Vimentin的表达，可能有助于上皮细胞的游走迁移，以形成早期原始腺体。CK5、CK18以及CK19阳性细胞在原始腺体中的动态分布与胚胎前列腺上皮细胞的分化状态有关。     

A protocol of selective antibiotic prophylaxis for Caesarean section based on risk factors

The aim of the study was to identify risk factors associated with increased risks of post Caesarean febrile morbidity from a retrospective epidemiological analysis, and to prospectively evaluate a protocol of selective antibiotic prophylaxis based on these risk factors. Caesarean section births over a three-year period--during which no antibiotic prophylaxis protocol was practised--were reviewed. Risk factors for febrile morbidity were identified using both univariate and multivariate analysis. A protocol of selective antibiotic prophylaxis, incorporating the significant risk factors identified, was then evaluated prospectively over a nine-month period. The incidence of febrile morbidity from the retrospective study was 16.9%. A logistic regression model, with febrile morbidity as the dependent variable, identified only the duration of labour over 10 hours as a significant factor. A protocol of antibiotic prophylaxis using intravenous ampicillin was then practised in the presence of these two factors. Evaluation of this protocol after nine months showed that the incidence of febrile morbidity was reduced significantly from 20% in those not given antibiotics to around 9.6% in those eligible for and given antibiotics. However, the overall incidence of febrile morbidity remained at around 16-18%.     

“Receptivity”: An Important Factor Affecting Supportive Care Provision

The research on psychosocial need provides the foundation informing the drive for the provision of supportive care services for patients and their families. The work on patient access, barriers to participation, and service evaluation are providing some insights that can help guide practitioners in their efforts to ensure that services designed to meet psychosocial need reach and involve the appropriate individuals. However, this direction is presently in its infancy leaving many questions unanswered. This article makes a contribution to advancing and strengthening this line of research through a fresh perspective on the topic provided by consumer research with individuals diagnosed with a hematological malignancy. The research was initiated and funded by the Leukaemia Foundation of Queensland (LFQ) with the aim of exploring the experience of survivorship for individuals diagnosed with a hematological malignancy to inform supportive care service provision and development. The findings from the research posit the notion of “receptivity” as an important new concept that can contribute to the deepening of our understanding of the myriad of factors associated with effectively engaging with individuals in supportive care service provision.     

Postoperative Use of Oral Sildenafil in Pediatric Patients with Congenital Heart Disease

We sought to determine the efficacy of postoperative oral sildenafil therapy (OST) in pediatric patients with congenital heart disease (CHD). A retrospective review of 45 postoperative patients with CHD who received OST was performed. Patients were categorized into three groups according to clinical indications: (1) to stabilize pulmonary vascular reactivity after biventricular repair (group 1 [n = 15]), (2) to lower pulmonary vascular resistance after bidirectional cavopulmonary shunt (group 2 [n = 12]), and (3) to improve post-Fontan hemodynamics (group 3 [n = 18]). Thirty-four patients (34 of 45 [75.6%]) had received inhaled nitric oxide (iNO) while on OST. Mean pulmonary arterial pressure (mPAP), mean systemic blood pressure (mSBP), and peripheral oxygen saturation (SpO₂) were recorded during the first 24 hours after the initiation of OST. In group 1, the baseline mPAP/mSBP ratio (0.60 ± 0.17) decreased significantly after the second (0.46 ± 0.14, p = 0.004) and fourth (0.50 ± 0.18, p = 0.025) doses of OST. In group 2, baseline SpO₂ (71.0 ± 12.3%) increased after the fourth dose (75.1 ± 12.3%, p = 0.04) of OST, without significant changes in mPAP. In group 3, baseline mPAP (14.8 ± 3.3 mmHg) decreased significantly after the first (13.9 ± 2.8 mmHg, p = 0.025) and second (13.3 ± 1.9 mmHg, p = 0.016) doses of OST, without changes in SpO₂. In thirty-one (31 of 34 [92%]) subjects, iNO was discontinued within a median of 2 days after the initiation of OST, without rebound phenomena. There were no OST-related complications. Sildenafil citrate can be used safely in postoperative pediatric patients with CHD. Benefits from OST may be manifested differently in various clinical settings.     

Associations between cytochrome P4502E1 genotype, mutagen sensitivity, cigarette smoking and susceptibility to lung cancer

Cytochrome P4502E1 (CYP2E1) is involved in the metabolic activation of carcinogenic N-nitrosoamines. We therefore assessed the genotype frequencies of PstI or RsaI CYP2E1 restriction fragment length polymorphisms and another susceptibility marker, mutagen sensitivity, in 137 lung cancer cases (92 African American and 45 Mexican American) and 206 controls (114 African American and 92 Mexican American) identified in a molecular epidemiological study of lung cancer. The CYP2E1 c1/c1 genotype was found in 86.7% of Mexican American cases, 70.6% of Mexican American controls, 89.1% of African American cases and 86.8% of African American controls. By multivariate analysis, this genotype was found to be associated with a 14.0-fold increased risk of lung cancer in Mexican Americans but not in African Americans; a 9.9- fold increased risk of lung cancer in Mexican American former smokers, but not in non-smokers or current smokers; a 15-fold increased risk of lung cancer in Mexican American males, but not in females. Patients with the susceptible genotype appeared to have developed cancer at an earlier age and with lower cigarette pack-year of exposure than did patients with the c1/c2 or c2/c2 genotypes. Stratified analysis suggested a greater than multiplicative interaction between cigarette smoking and CYP2E1 c1/c1 genotype, although not statistically significant. The odds ratios (ORs) for the CYP2E1 c1/c1 genotype, cigarette smoking and both risk factors combined were 1.3, 6.7 and 16.3, respectively. The association between CYP2E1 c1/c1 genotype and pack-years of smoking followed the same pattern. The interaction between mutagen sensitivity and CYP2E1 c1/c1 genotype was especially strong in former smokers (the ORs for the CYP2E1 c1/c1 genotype, mutagen sensitivity and both risk factors combined were 3.9, 5.4 and 23.0, respectively). Therefore, the data suggest that individuals who lack a c2 allele might be at higher risk for developing lung cancer.