PAI-I 4G/5G polymorphism and sudden cardiac death in patients with coronary artery disease.

The 4G/5G polymorphism of the plasminogen activator inhibitor type I (PAI-I) gene is involved in coronary artery disease (CAD), with the highest risk in 4G/4G homozygotes. The role of PAI-I polymorphism in patients suffering from CAD and history of sudden cardiac death (SCD) has not been addressed yet. We studied the frequency distribution of the PAI-I gene to test the hypothesis that the 4G/4G genotype favors myocardial ischemia and, even in the absence of acute infarction, promotes SCD in patients with CAD. Methods: The PAI-I 4G/5G genotypes and PAI-I antigen plasma levels were determined in 97 patients with CAD and a history of SCD treated with an implantable cardioverter defibrillator (ICD) (defibrillator group) comparing to 113 patients with CAD but no history of SCD (control group). Results: The defibrillator group consisted of significantly more 4G/4G homozygotes and higher PAI-I levels than the control group (44% vs. 24%, 173+/-41 vs. 144+/-49 ng/ml; P<.01). The carriers of 4G allele had a significantly higher risk for SCD (odds ratio (OR) 1.9) with the highest risk in the 4G/4G genotype (OR 3.6, P<.01). Conclusion: These results suggest that the PAI-I 4G/4G genotype is associated with SCD in patients suffering from CAD.     

Graves' ophthalmopathy and gene polymorphisms in interleukin-1α, interleukin-1β, interleukin-1 receptor and interleukin-1 receptor antagonist

Purpose: Interleukin‐1 (IL‐1) is known to have an important role in pathogenesis of Graves' ophthalmopathy (GO). Polymorphisms in IL‐1 gene have been associated with autoimmune reactions. This study aimed to investigate the association of GO with single‐nucleotide polymorphisms (SNPs) in the IL‐1 family (IL‐1α, IL‐1β, IL‐1 receptor [IL‐1R] and IL‐1 receptor antagonist [IL‐1RA]). Methods: A total of 57 patients of Graves' disease without GO, 50 patients with GO and 140 healthy controls were enrolled. Patients were recruited consecutively from the outpatient endocrine clinic of a large university general hospital. Cytokine typing was performed by the polymerase chain reaction with sequence‐specific primers assay. The allele and genotype frequencies of the following polymorphisms were determined: IL‐1α (?889C/T), IL‐1β (?511C/T), IL‐1β (+3962C/T), IL‐1R (Pst‐1 1970C/T) and IL‐1RA (Mspa‐1 11100C/T). Genotype distributions among patients were in Hardy–Weinberg equilibrium for all polymorphisms. Results: Among the five SNPs studied, the frequencies of the T allele and the TT genotype of IL‐1α (?889C/T) were significantly higher among patients with GO than those without GO (odds ratio [OR] = 2.16, 95% confidence interval [CI] = 1.25–3.74; P = 0.006 and 5.67, 95% CI = 1.66–49.34; P = 0.005, respectively). For IL‐1RA (Mspa‐1 11100C/T), the frequencies of the C allele and the CC genotype were significantly higher among patients with GO (OR = 2.31, 95% CI = 1.34–4.00; P = 0.004 and 6.73 95% CI = 1.94–23.36; P = 0.004, respectively; P < 0.01). No significant association was found for other SNPs. Conclusion: This is the first study to show a positive correlation between polymorphisms in the IL‐1α and IL‐1RA genes and susceptibility to GO. These findings promote further research into genetic correlates of GO.     

Further studies on the mechanisms for the antithrombotic effects of sulfated polysaccharides in rabbits

A recent study (Fernandez et al., Thromb. Haemostas. 1987; 57: 286-93) demonstrated that when rabbits were injected with the minimum weight of a variety of glycosaminoglycans required to inhibit tissue factor-induced thrombus formation by approximately 80%, exogenous thrombin was inactivated approximately twice as fast in the post-treatment plasmas as the pre-treatment plasmas. In this study, we investigated the relationship between inhibition of thrombus formation and the extent of thrombin inhibition ex vivo. We also investigated the relationship between inhibition of thrombus formation and inhibition of prothrombin activation ex vivo. Four sulfated polysaccharides (SPS) which influence coagulation in a variety of ways were used in this study. Unfractionated heparin and the fraction of heparin with high affinity to antithrombin III potentiate the antiproteinase activity of antithrombin III. Pentosan polysulfate potentiates the activity of heparin cofactor II. At less than 10 micrograms/ml of plasma, all three SPS also inhibit intrinsic prothrombin activation. The fourth agent, dermatan sulfate, potentiates the activity of heparin cofactor II but fails to inhibit intrinsic prothrombin activation even at concentrations which exceed 60 micrograms/ml of plasma. Inhibition of thrombus formation by each sulfated polysaccharides was linearly related to the extent of thrombin inhibition achieved ex vivo. These observations confirm the utility of catalysis of thrombin inhibition as an index for assessing antithrombotic potential of glycosaminoglycans and other sulfated polysaccharides in rabbits. With the exception of pentosan polysulfate, there was no clear relationship between inhibition of thrombus formation and inhibition of prothrombin activation ex vivo.     

An approach to assigning in vitro potency to unfractionated and low molecular weight heparins based on the inhibition of prothrombin activation and catalysis of thrombin inhibition

Unfractionated and low molecular weight (LMW) heparins with good antithrombotic activity invariably catalyze thrombin inhibition and inhibit the appearance of thrombin activity in contact-activated plasma. Conversely, the antithrombotic efficacy of LMW heparins decreases as their ability to catalyze thrombin inhibition and to inhibit the appearance of thrombin activity in plasma decrease. The activated partial thromboplastin time (APTT) has proven a reliable test for assaying unfractionated heparin. We therefore compared 2 unfractionated and 3 LMW heparins on the basis of the minimum concentrations required to double the APTT of normal plasma and by then determined how this anticoagulant effect was achieved. The amount of unfractionated and LMW heparin which doubled the APTT was found to be equivalent to approximately 0.25 antithrombin units. This concentration of each glycosaminoglycan completely inhibited prothrombin activation for 45 s after CaCl2 was added to contact-activated plasma; accelerated thrombin inhibition by purified antithrombin III by approximately 50-fold; and accelerated thrombin inhibition equally by antithrombin III in undiluted plasma. This concentration of the three LMW heparins increased, by approximately 70-fold, the rate of factor Xa inhibition by purified antithrombin III compared to the 50-fold increase seen with the two unfractionated heparins. These results thus suggest that tests based on the inhibition of prothrombin activation and/or on the catalysis of thrombin inhibition provide a useful basis for assigning in vitro potency to both unfractionated and LMW heparins.     

Long-term impact of bariatric surgery on glycemic control and glucose-lowering therapy for people with type 2 diabetes: population-based cohort study

BackgroundRandomized controlled trials (RCTs) have demonstrated that bariatric surgery improves glycemic control among people with diabetes. However, evidence from RCTs may not be generalizable to real-world clinical care with unselected patients in routine clinical practice.ObjectivesTo examine long-term glycemic control and glucose-lowering drug regimens following bariatric surgery for people with type 2 diabetes (T2D) in unselected patients in routine clinical practice.SettingPopulation-based cohort study using linked routinely collected real-world data from Ontario, Canada.MethodsIndividuals with T2D who were assessed for bariatric surgery at any referral center in the province between February 2010 and November 2016 were identified and divided into those who received surgery within 2 years of the initial assessment and those who did not.ResultsThere were 3674 people who had bariatric surgery and 1335 who did not. By 2 years, people who had undergone surgery had a significantly lower HbA1C (6.3 ± 1.2 % versus 7.8 ± 1.8 %, P < .0001), and this difference persisted at 3, 4, 5, and 6 years. Even by 6 years, half of those who had undergone surgery remained on no glucose-lowering drugs, and they were nearly 6 times less likely to be on insulin than those who had not undergone surgery.ConclusionsIn real-world clinical care, bariatric surgery was associated with large and sustained improvements in glycemic control.     

Adrenal Biopsy under Wide-Bore MR Imaging Guidance

Twenty-four magnetic resonance (MR) imaging–guided percutaneous adrenal biopsies performed between April 2009 and October 2016 were reviewed retrospectively. Epidemiologic, procedural, and histopathologic data were retrospectively collected. Mean size of tumors was 4.3 cm (range, 1.5–16.0 cm). Mean procedure time was 49 min (range, 24–95 min). Mean needle angulation was 27.7° (range, 0°–60°). Mean depth was 9.6 cm (range, 5.8–13.7 cm). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MR imaging–guided biopsy were 95.5%, 100%, 100%, 66.7%, and 95.8%, respectively. There were no immediate or delayed complications. MR imaging guidance seems safe and accurate to target adrenal-gland masses.     

Association of perturbation of oral bacterial with incident of Alzheimer's disease: A pilot study

ObjectiveThis case‐control study was designed to compare the composition of the predominant oral bacterial microbiome in Alzheimer''s disease (AD) and control group.SubjectA total of 30 adult participants (15 AD and 15 healthy individuals) were entered in this study. The composition of oral bacterial microbiome was examined by quantitative real‐time polymerase chain reaction (qPCR) using bacterial 16S rDNA gene. The levels of systemic inflammatory cytokines in both groups were assessed using enzyme‐linked immunosorbent assays (ELISA).ResultsThe loads of Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia were significantly more abundant in the AD compared to the control group (p < 0.05). Although Aggregatibacter actinomycetemcomitans and Streptococcus mutans were relatively frequent in the AD group, no significance difference was observed in their copy number between two groups. Although the concentrations of IL‐1, IL‐6, and TNF‐α were higher in the AD group, there was a significant difference in their levels between the two groups (p < 0.05). Finally, there was a significant relationship between increased number of pathogenic bacteria in oral microbiome and higher concentration of cytokines in patient''s blood.ConclusionOur knowledge of oral microbiome and its exact association with AD is rather limited; our study showed a significant association between changes in oral microbiome bacteria, increased inflammatory cytokines, and AD.