The Role of Asymmetric Dimethylarginine (ADMA) in Endothelial Dysfunction and Cardiovascular Disease

Endothelium plays a crucial role in the maintenance of vascular tone and structure. Endothelial dysfunction is known to precede overt coronary artery disease. A number of cardiovascular risk factors, as well as metabolic diseases and systemic or local inflammation cause endothelial dysfunction. Nitric oxide (NO) is one of the major endothelium derived vaso-active substances whose role is of prime importance in maintaining endothelial homeostasis. Low levels of NO are associated with impaired endothelial function. Asymmetric dimethylarginine (ADMA), an analogue of L-arginine, is a naturally occurring product of metabolism found in human circulation. Elevated levels of ADMA inhibit NO synthesis and therefore impair endothelial function and thus promote atherosclerosis. ADMA levels are increased in people with hypercholesterolemia, atherosclerosis, hypertension, chronic heart failure, diabetes mellitus and chronic renal failure. A number of studies have reported ADMA as a novel risk marker of cardiovascular disease. Increased levels of ADMA have been shown to be the strongest risk predictor, beyond traditional risk factors, of cardiovascular events and all-cause and cardiovascular mortality in people with coronary artery disease. Interventions such as treatment with L-arginine have been shown to improve endothelium-mediated vasodilatation in people with high ADMA levels. However the clinical utility of modifying circulating ADMA levels remains uncertain.     

A total system approach to sustainable pest management

A fundamental shift to a total system approach for crop protection is urgently needed to resolve escalating economic and environmental consequences of combating agricultural pests. Pest management strategies have long been dominated by quests for “silver bullet” products to control pest outbreaks. However, managing undesired variables in ecosystems is similar to that for other systems, including the human body and social orders. Experience in these fields substantiates the fact that therapeutic interventions into any system are effective only for short term relief because these externalities are soon “neutralized” by countermoves within the system. Long term resolutions can be achieved only by restructuring and managing these systems in ways that maximize the array of “built-in” preventive strengths, with therapeutic tactics serving strictly as backups to these natural regulators. To date, we have failed to incorporate this basic principle into the mainstream of pest management science and continue to regress into a foot race with nature. In this report, we establish why a total system approach is essential as the guiding premise of pest management and provide arguments as to how earlier attempts for change and current mainstream initiatives generally fail to follow this principle. We then draw on emerging knowledge about multitrophic level interactions and other specific findings about management of ecosystems to propose a pivotal redirection of pest management strategies that would honor this principle and, thus, be sustainable. Finally, we discuss the potential immense benefits of such a central shift in pest management philosophy.     

Aortic Dissection Caused by Percutaneous Coronary Intervention: 2 New Case Reports and Detailed Analysis of 86 Previous Cases

Aortic dissection, a rare sequela of percutaneous coronary intervention, can be fatal when it is not recognized and treated promptly. Treatment varies from conservative management to invasive aortic repair and revascularization. We report the cases of 2 patients whose aortic dissection was caused by percutaneous coronary intervention. In addition, we present detailed analyses of 86 previously reported cases. Aortic dissection was most often seen during intervention to the right coronary artery (in 76.7% of instances). The 2 most frequently reported causes were catheter trauma (in 54% of cases) and balloon inflation (in 23.8%). The overall mortality rate was 7.1%. We conclude that most patients can be treated conservatively or by means of stenting alone, with no need for surgical intervention.     

Kinetics of liver regeneration in donors after living donor liver transplantation: A retrospective analysis of “2/3rd partial hepatectomy” model at 3 months

Background/Aim

Right lobe living donor (2/3rd partial hepatectomy) model is the best way to accurately study liver regeneration process in human beings. We aimed to study the kinetics of liver regeneration after 2/3rd partial hepatectomy in donors.

Methods

Retrospective analysis of prospectively maintained volumetric recovery data in donors was performed in 23 donors, who underwent 29 contrast-enhanced computed tomography within 3 months for various clinical indications.

Results

The absolute volumetric growth percentages were as follows: 37.60?±?21.74 at 1st week, 92?±?53.27 at 2nd week, 115.55?±?59.65 at 4th week, and 110.79?±?64.47 at 3 months. On sub-group analysis of our cohort, we found that 4.3%, 17%, 30.4%, and 39% donors attended ≥?90% volumetric recovery at 1st, 2nd, 4th week, and 3 months, respectively. One patient at 4th week revealed 128% volumetric recovery. There was one more patient who exceeded original total liver volumes (TLV) (111% of TLV) at 2.5 months. The serum bilirubin and INR values peaked at postoperative day (POD) 3rd and then started showing a downward trend from POD 5th onwards.

Conclusion

Our study is the first to document complete volumetric recovery in donors as early as 3 weeks. Two of the donors overshot their original TLV during the early regenerative phase.

     

Detection of Barrett's esophagus after endoscopic healing of erosive esophagitis

BACKGROUND: The presence of erosive esophagitis (EE) in patients presenting for upper endoscopy may prevent the detection of underlying Barrett's esophagus (BE) in the distal esophagus. AIM: To prospectively determine the proportion of patients detected with BE upon repeat endoscopy after healing of EE. METHODS: Patients with endoscopically confirmed EE without BE were treated with standard doses of acid suppression therapy and a repeat endoscopy was performed to assess the presence of BE. If columnar mucosa was visualized in the distal esophagus, targeted biopsies were obtained and all biopsies were evaluated for the presence of intestinal metaplasia. BE was defined as columnar mucosa in the distal esophagus with intestinal metaplasia on biopsy. RESULTS: A total of 172 patients with reflux symptoms were diagnosed with EE without BE on initial endoscopy. They were treated with standard doses of proton pump inhibitor therapy, and after a mean duration of 11 wk (range 8-16 wk), a repeat endoscopy was performed to confirm healing of EE and to document the presence of BE. On repeat endoscopy, EE was completely healed in 116 patients (67%), and of those, BE was suspected in 32 patients (i.e., columnar-lined distal esophagus) and was confirmed in 16 patients (13.8%). In the 56 patients with persistent EE on repeat endoscopy, columnar mucosa in areas of previously healed esophagitis was visualized in 8 and confirmed in 5 patients (8.9% of nonhealed cases). Overall, 21 (12%) patients were confirmed with BE on repeat endoscopy; all men, mean age 61 yr with a median BE length of 0.5 cm (range 0.5-5 cm, interquartile range 0.5 cm). The majority of these patients (N = 19) had short segment Barrett's esophagus (SSBE) (i.e., length <3 cm). CONCLUSIONS: In patients with EE undergoing treatment with acid suppressive therapy, BE (mainly SSBE) is detected in approximately 12% of patients on repeat endoscopy. Patients with reflux symptoms undergoing endoscopy for the detection of BE (i.e., screening) should be treated with acid suppressive therapy prior to endoscopy to enhance the yield of BE. Alternatively, if the goal is to document BE and if EE is found at the initial endoscopy, then repeat endoscopy may be considered after acid suppressive therapy.     

Magnetic resonance imaging findings in an unusual case of atlanto axial dislocation and vertebral artery–vein fistulas in a patient of neurofibromatosis‐1

Vertebral arteriovenous fistulas are uncommon in neurofibromatosis. We describe MRI findings of a patient with an unusual association of bilateral vertebral arteriovenous fistulas with an atlantoaxial dislocation in the setting of neurofibromatosis.     

Reduced sarcoplasmic reticulum Ca2+ uptake and increased Na+–Ca2+ exchanger expression in left ventricle myocardium of dogs with progression of heart failure

Alteration of intracellular Ca²⁺ homeostasis in failing cardiomyocytes is associated with changes in regulatory proteins located in the sarcoplasmic reticulum (SR) and sarcolemma, which participate in Ca²⁺ fluxes across the membrane during the cardiac cycle. These regulatory proteins include Ca²⁺-ATPase (SERCA 2A), phospholamban (PLB), ryanodine-sensitive Ca²⁺ release channels (RR), and the sarcolemmal Na⁺–Ca²⁺ exchanger (NCX). Although their status is known in failed myocardium, it is poorly understood during the progression of heart failure (HF), particularly in large animals. We studied the left ventricular (LV) myocardium of six dogs with moderate HF and six with severe HF produced by multiple intracoronary microembolizations, compared with six normal dogs (NL). Oxalate-dependent SR Ca²⁺ uptake and expression of SERCA 2A, PLB, phosphorylated PLB at serine 16 (PLB-Ser) and threonine 17 (PLB-Thr), RR, and NCX were determined. Percent LV ejection fraction declined by 47% compared with NL (34.1% ± 1% vs 64% ± 2%) in dogs with moderate HF (HF-2W) 2 weeks after the last embolization and by 42% (20.5% ± 1% vs 34.1% ± 1%) in dogs with severe HF (HF-4M) at 4 months compared with HF-2W. Left ventricular pressure during isovolumic contraction (+dP/dt, mmHg/s) and relaxation (–dP/dt, mmHg/s) was significantly reduced in severe compared with moderate HF. Oxalate-dependent SR Ca²⁺ uptake (nmol ⁴⁵Ca²⁺ accumulated/min per milligram noncollagen protein) declined by 25% (21.3 ± 1 vs 28.5 ± 2) in HF-2W and 49% in HF-4M. Protein expression of SERCA 2A and PLB decreased by 67% and 35%, respectively, in HF-2W compared with NL, whereas SERCA 2A expression increased by 167% and PLB decreased by 40% in HF-4M compared with HF-2W. However, SERCA 2A protein was still significantly lower in HF-4M compared with NL. PLB-Ser and PLB-Thr increased significantly in HF-2W but decreased in HF-4M compared with NL. Similar changes in mRNA encoding PLB and SERCA 2A were observed in dogs with moderate and severe HF. The RR protein level declined in dogs with moderate and severe HF, whereas NCX protein did not change with moderate HF but increased with sever HF. These results suggest that the regulatory proteins responsible for Ca²⁺ uptake, Ca²⁺ release, and Na⁺–Ca²⁺ exchange are critically associated with the deterioration of LV function during the progression of HF.     

Risk stratification of Barrett's esophagus: updated prospective multivariate analysis

OBJECTIVES: Prospective evaluation of Barrett's esophagus (BE) in order to determine what demographic, endoscopic, and histologic features are predictive of the prevalence and incidence of Barrett's high-grade dysplasia (HGD) and adenocarcinoma (Ca). METHODS: Newly diagnosed BE patients were entered into and followed in a standardized surveillance protocol. The following features were examined using either forward, stepwise multiple regression analysis, or Cox proportional hazards to determine their ability to predict the presence of HGD or Ca at index BE diagnosis as well as their ability to predict progression of BE during follow-up: age, race, gender, length of BE in cm, size of a hiatal hernia, severity of dysplasia at index diagnosis as well as during surveillance, gastric Helicobacter pylori infection status, and type of medical acid-reflux treatment. RESULTS: A total of 550 patients were diagnosed with BE over the study period. Stepwise multiple regression analysis showed three factors significantly associated with index diagnosis of HGD or Ca: hiatal hernia (larger size), Barrett's length (longer length), and absence of H. pylori infection. Three hundred and twenty-four BE entered the surveillance protocol. Cox proportional hazards models revealed a significant and independent association for five factors predictive of the time to progression of BE: presence of dysplasia at index diagnosis (p < 0.001), severity of dysplasia during surveillance (p < 0.001), length of Barrett's epithelium (p= 0.012), size of hiatal hernia (p= 0.006), and gastric H. pylori infection status (p= 0.023). CONCLUSIONS: Endoscopic and histologic features of BE at initial diagnosis are predictive of index HGD and cancer as well as with risk of BE progression.