Oral ascorbic acid in combination with beta-blockers is more effective than beta-blockers alone in the prevention of atrial fibrillation after coronary artery bypass grafting

Because adrenergic beta antagonists are not sufficient to prevent atrial fibrillation after coronary artery bypass grafting, this prospective, randomized trial was designed to evaluate the effects of ascorbic acid as an adjunct to beta-blockers. Fifty patients formed our ascorbic acid group, and another 50 patients formed our control group. All patients were older than 50 years, were scheduled to undergo coronary artery bypass grafting, and had been treated with beta-blockers for at least 1 week before surgery. The mean age of the population was 60.19+/-7.14 years; 67% of the patients were men. Patients in the ascorbic acid group received 2 g of ascorbic acid on the night before the surgery and 1 g twice daily for 5 days after surgery. Patients in the control group received no ascorbic acid. Patients in both groups continued to receive beta-blockers after surgery. Telemetry monitoring was performed in the intensive care unit, and Holter monitoring was performed for 4 days thereafter. The incidence of postoperative atrial fibrillation was 4% in the ascorbic acid group and 26% in the control group (odds ratio, 0.119; 95% confidence interval, 0.025-0.558, P = 0.002). We conclude that ascorbic acid is effective, in addition to being well-tolerated and relatively safe. Therefore, it can be prescribed as an adjunct to beta-blockers for the prophylaxis of post-bypass atrial fibrillation.     

Carbon dioxide absorber as a cause of high airway pressures

We investigate an incident in which a carbon dioxide absorber caused difficulty with ventilation. The problem as it developed throughout the anesthetic, and clues that led to the determination that the carbon dioxide canister was the problem, is discussed.     

Impact of baseline platelet count in patients undergoing primary percutaneous coronary intervention in acute myocardial infarction (from the CADILLAC trial)

Despite the well-recognized role of platelets in the pathogenesis of acute myocardial infarction (AMI) and in the vascular responses to angioplasty, the relation between platelet count and outcomes after primary percutaneous coronary intervention (PCI) in AMI is unknown. We therefore determined the effect of baseline platelet count on clinical and angiographic outcomes of patients with AMI undergoing primary PCI. In the prospective, randomized CADILLAC trial, platelet count on admission was available in 2,021 of 2,082 patients (97.0%). Angiographic results and outcomes at 30 days and 1 year were stratified by quartiles of platelet count. Median platelet count was 231 x 10(9)/L (range 38 to 709). Primary PCI angiographic success rates were independent of platelet count. The 30-day incidence of target vessel thrombosis or reocclusion increased steadily across the higher quartiles of baseline platelet count (0.2%, 0.6%, 1.0%, and 2.0%, p = 0.027). At 1 year, patients with a baseline platelet count >or=234 versus <234 x 10(9)/L had higher rates of death or reinfarction (8.9% vs 4.5%, p <0.0001), death (5.8% vs 3.1%, p = 0.002), and reinfarction (3.4% vs 1.6%, p = 0.008). By multivariable analysis, a higher baseline platelet count was the strongest predictor of 1-year death or reinfarction (hazard ratio [HR] per 10,000 increase in platelet count 1.02, 95% confidence interval [CI] 1.02 to 1.07, p <0.0001) and independently predicted reinfarction (HR 1.06, 95% CI 1.02 to 1.09, p = 0.002) and cardiac mortality (HR 1.03, 95% CI 1.00 to 1.06, p = 0.055) at 1 year. In conclusion, a higher baseline platelet count in patients with AMI is a powerful independent predictor of death and reinfarction within the first year after primary PCI.     

Impaired perfusion after myocardial infarction is due to reperfusion-induced deltaPKC-mediated myocardial damage

OBJECTIVE: To improve myocardial flow during reperfusion after acute myocardial infarction and to elucidate the molecular and cellular basis that impedes it. According to the AHA/ACC recommendation, an ideal reperfusion treatment in patients with acute myocardial infarction (AMI) should not only focus on restoring flow in the occluded artery, but should aim to reduce microvascular damage to improve blood flow in the infarcted myocardium. METHODS: Transgenic mouse hearts expressing the deltaPKC (protein kinase C) inhibitor, deltaV1-1, in their myocytes only were treated with or without the deltaPKC inhibitor after ischemia in an ex vivo AMI model. deltaV1-1 or vehicle was also delivered at reperfusion in an in vivo porcine model of AMI. Microvascular dysfunction was assessed by physiological and histological measurements. RESULTS: deltaPKC inhibition in the endothelial cells improved myocardial perfusion in the transgenic mice. In the porcine in vivo AMI model, coronary flow reserve (CFR), which is impaired for 6 days following infarction, was improved immediately following a one-minute treatment at the end of the ischemic period with the deltaPKC-selective inhibitor, deltaV1-1 ( approximately 250 ng/kg), and was completely corrected by 24 h. Myocardial contrast echocardiography, electron microscopy studies, and TUNEL staining demonstrated deltaPKC-mediated microvascular damage. epsilonPKC-induced preconditioning, which also reduces infarct size by >60%, did not improve microvascular function. CONCLUSIONS: These data suggest that deltaPKC activation in the microvasculature impairs blood flow in the infarcted tissue after restoring flow in the occluded artery and that AMI patients with no-reflow may therefore benefit from treatment with a deltaPKC inhibitor given in conjunction with removal of the coronary occlusion.     

Thymoquinone Attenuates Astrogliosis, Neurodegeneration, Mossy Fiber Sprouting, and Oxidative Stress in a Model of Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is a rather common and difficult-to-treat variant of epilepsy. Nearly one third of people with epilepsy do not respond effectively to currently available anticonvulsants. In this study, we evaluated the protective effect of thymoquinone (TQ), the main constituent of black seed with antioxidant and anti-inflammatory effects, in the intrahippocampal kainate model of TLE in rat. Following kainate injection, seizure activity was observed that was significantly diminished by TQ pretreatment at a dose of 10 mg/kg, p.o. Intrahippocampal kainate also increased malondialdehyde (MDA), nitrite, and nitrate levels and decreased activity of superoxide dismutase and TQ only significantly attenuated MDA. In addition, intrahippocampal kainate caused a significant reduction of neurons in CA1, CA3 and the hilar regions, and TQ significantly attenuated these changes. Timm histochemistry showed a marked mossy fiber sprouting (MFS) in the dentate gyrus of kainate-lesioned rats, and TQ significantly lowered MFS intensity. Meanwhile, a number of reactive astrocytes (astrogliosis) increased significantly in the kainate group, and TQ pretreatment significantly decreased it. These data suggest that TQ pretreatment could attenuate seizure activity and lipid peroxidation, lower hippocampal neuronal loss and MFS, and mitigate astrogliosis in kainate model of TLE.     

Hyperkalemia and Hypertension Post Organ Transplantation – A Management Challenge

Potassium is the most important intracellular cation and the kidneys play a pivotal role in potassium homeostasis. Potassium disorder is a common electrolyte abnormality and it increases the risk of death from any cause, particularly cardiovascular events. Hyperkalemia is a common electrolyte abnormality encountered post organ transplantation. The etiology is multifactorial, and includes drugs such as calcineurin inhibitors. In certain regards, the clinical picture of post-transplantation hyperkalemia and hypertension resembles that of Gordon syndrome or familial hyperkalemic hypertension, a disorder characterized by over activity of thiazide-sensitive sodium chloride cotransporter. Effective and safe management of chronic hyperkalemia can be challenging in this special patient population. Despite the significant short-term and long-term side effects, fludrocortisone (a potent synthetic oral mineralocorticoid receptor agonist) has emerged as the default drug of choice for treatment of refractory hyperkalemia in many organ transplant recipients. However, the long-term efficacy and safety of fludrocortisone for management of hyperkalemia in organ transplant recipients remains unknown. This review discusses potassium homeostasis, including the role of the kidneys, and focuses on calcineurin inhibitor-induced hyperkalemia and on the under-appreciated role of thiazide-type diuretic use in management of hyperkalemia and hypertension. We present an illustrative case of post-transplantation hyperkalemia and hypertension with relevant literature.     

The quinazoline-2,4(1H,3H)-diones skeleton: A key intermediate in drug synthesis

Quinazoline-2,4(1H,3H)-dione is a major class of N-fused heterocyclic with a wide range of biological functions, including anti-HIV, anticancer, antifungal, antibacterial, antimutagenic, anticoccidial, anticonvulsant, anti-inflammatory, antidepressant, antimalarial, antioxidant, antileukemic, and antileishmanial activities, and other activities, has attracted high attention in organic and medicinal chemistry. As a consequence, all chemists and pharmaceutical chemists should be familiar with the various procedures for producing quinazoline-2,4(1H,3H)-dione. The main purpose of this paper is to provide an overview of the many manufacturing methods for various biological compounds based on the quinazoline-2,4(1H,3H)-dione and 2,4-dichloroquinazoline cores.     

Resuming Breast Imaging Services in the Aftermath of the COVID-19 Pandemic: Safety and Beyond

As the Coronavirus disease 2019 (COVID-19) epidemic begins to stabilize, different medical imaging facilities not directly involved in the COVID-19 epidemic face the dilemma of how to return to regular operation. We hereby discuss various fields of concern in resuming breast imaging services. We examine the concerns for resuming functions of breast imaging services in 2 broad categories, including safety aspects of operating a breast clinic and addressing potential modifications needed in managing common clinical scenarios in the COVID-19 aftermath. Using a stepwise approach in harmony with the relative states of the epidemic, health care system capacity, and the current state of performing breast surgeries (and in compliance with the recommended surgical guidelines) can ensure avoiding pointless procedures and ensure a smooth transition to a fully operational breast imaging facility.     

Reduction of surgical site infections by use of pulsatile lavage irrigation after prolonged intra-abdominal surgical procedures

Background

Surgical site infections cause significant postoperative morbidity and may be reduced by pressurized irrigation of high-risk laparotomy wounds before closure. This was a retrospective review (June 2007 to May 2008) from a surgical unit at a tertiary care center.

Methods

Patients undergoing laparotomy extending beyond 4 hours, when a standard wound management strategy was instituted by either simple irrigation or pressurized pulsatile lavage (<15 psi) with saline before closure, were included. The outcome measures were the surgical site infections and factors contributing to them.

Results

The median surgical time for the patients was 8 hours, with 34 wounds managed by simple irrigation and 42 wounds managed by pulse irrigation. Both groups had similar characteristics. Overall there were 15 (20%) surgical site infections. Significantly fewer infections occurred in the pulse irrigation group (10% vs 32%; P = .019). The use of a pulse irrigation device was the only factor associated with a reduction in wound infections (P = .019).

Conclusions

Surgical site infections appear to be reduced with pulsatile lavage irrigation of wounds before skin closure in patients undergoing prolonged intra-abdominal surgeries.