Revascularization of the Posterior Circulation

The primary objective of revascularization procedures in the posterior circulation is the prevention of vertebrobasilar ischemic stroke. Specific anatomical and neurophysiologic characteristics such as posterior communicating artery size affect the susceptibility to ischemia. Current indications for revascularization include symptomatic vertebrobasilar ischemia refractory to medical therapy and ischemia caused by parent vessel occlusion as treatment for complex aneurysms. Treatment options include endovascular angioplasty and stenting, surgical endarterectomy, arterial reimplantation, extracranial-to-intracranial anastomosis, and indirect bypasses. Pretreatment studies including cerebral blood flow measurements with assessment of hemodynamic reserve can affect treatment decisions. Careful blood pressure regulation, neurophysiologic monitoring, and neuroprotective measures such as mild brain hypothermia can help minimize the risks of intervention. Microscope, microinstruments and intraoperative Doppler are routinely used. The superficial temporal artery, occipital artery, and external carotid artery can be used to augment blood flow to the superior cerebellar artery, posterior cerebral artery, posterior inferior cerebellar artery, or anterior inferior cerebellar artery. Interposition venous or arterial grafts can be used to increase length. Several published series report improvement or relief of symptoms in 60 to 100% of patients with a reduction of risk of future stroke and low complication rates.     

A high fidelity tissue-based cardiac surgical simulator.

OBJECTIVE: Issues concerning the training and certification of surgical specialists have taken on great significance in the last decade. A realistic computer-assisted, tissue-based simulator developed for use in the training of cardiac surgical residents in the conduct of a variety of cardiac surgical procedures in a low-volume cardiothoracic surgery unit of a typical developing country is described. The simulator can also be used to demonstrate the function of technology specific to cardiac surgical procedures in a way that previously has only been possible via the conduct of a procedure on a live animal or human being. METHODS: A porcine heart in a novel simulated operating theatre environment with real-time simulated haemodynamic monitoring and coronary blood flow, in arrested and beating-heart modes, is used as a training tool for surgical residents. RESULTS: Standard and beating-heart coronary arterial bypass, aortic valve replacement, aortic homograft replacement and pulmonary autograft procedures can be simulated with high degrees of realism and with the superimposition of adverse clinical scenarios requiring valid decision making and clinical judgments to be made by the trainees. CONCLUSIONS: The cardiac surgical simulation preparation described here would appear to be able to contribute positively to the training of residents in low-volume centres, as well as having the potential for application in other settings as a training tool or clinical skills assessment or accreditation device. Collaboration with larger centres is recommended in order to accurately assess the utility of this preparation as an adjunctive cardiothoracic surgical training aid.     

Minimal Acute Rejection after Lung Transplantation: A Risk for Bronchiolitis Obliterans Syndrome

Bronchiolitis obliterans syndrome (BOS) is a major cause of lung allograft dysfunction. Although previous studies have identified mild to severe rejection (grade>or=A2) as a risk factor for BOS, the role of minimal rejection (grade A1) remains unclear. To determine if A1 rejection by itself is a risk factor for BOS, we performed a retrospective cohort study on 228 adult lung transplant recipients over a 7-year period. Cohorts were defined by their most severe rejection episode (none, A1 only, and >or=A2) and analyzed for the subsequent development and progression of BOS using univariate and multivariate time-dependent Cox regression analysis. In the univariate model, the occurrence of isolated minimal rejection was a risk factor for all stages of BOS. Similarly, multivariate models that included HLA mismatch, cytomegalovirus pneumonitis, community acquired viral infection, underlying disease and type of transplant demonstrated that A1 rejection was a distinct risk factor for BOS. Furthermore, the associated risk with A1 rejection was slightly greater than the risk from >or=A2 and treatment of A1 rejection decreased the risk for subsequent BOS stage 1. We conclude that minimal rejection is associated with an increased risk for BOS development and progression that is comparable to A2 rejection.     

Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness.

BACKGROUND: Partial response, no response, or residual symptoms following antidepressant therapy is common in clinical psychiatry. This study evaluated modafinil in patients with major depressive disorder (MDD) who were partial responders to adequate selective serotonin reuptake inhibitor (SSRI) therapy and excessive sleepiness and fatigue. METHODS: This retrospective analysis pooled the data of patients (18-65 yrs) who participated in two randomized, double-blind, placebo-controlled studies of modafinil (6-week, flexible-dose study of 100-400 mg/day or 8-week, fixed-dose study of 200 mg/day) plus SSRI therapy. Patients (n=348) met criteria for several residual symptoms (Epworth Sleepiness Scale [ESS] score>or=10; 17-item Hamilton Depression Scale [HAM-D] score between 4 and 25; and Fatigue Severity Scale [FSS] score>or=4). RESULTS: Compared to placebo, modafinil augmentation rapidly (within 1 week) and significantly improved overall clinical condition (Clinical Global Impression-Improvement), wakefulness (ESS), depressive symptoms (17-item HAM-D), and fatigue (FSS) (p<.01 for all). At final visit, patients receiving modafinil augmentation experienced statistically significant improvements in overall clinical condition, wakefulness, and depressive symptoms. Modafinil was well tolerated in combination with SSRI. CONCLUSIONS: Results of this pooled analysis provide further evidence suggesting that modafinil is an effective and well-tolerated augmentation therapy for partial responders to SSRI therapy, particularly when patients continue to experience fatigue and excessive sleepiness.     

Safety considerations of intranasal corticosteroids for the treatment of allergic rhinitis.

Allergic rhinitis (AR) is a major chronic inflammatory disease of the upper airways. AR is increasing in prevalence and causes negative effects on quality of life, impairs performance and productivity, and imposes a serious economic burden. More than 20% of the American population suffers from AR. Intranasal corticosteroids (INS) are an effective and safe first-line treatment for AR, with potent anti-inflammatory properties and a high therapeutic ratio. The systemic bioavailability of the majority of INS is relatively low; however, the pharmacokinetics of absorption, first-pass metabolism, volume of distribution, half-life, and clearance of INS varies considerably, depending on lipophilicity, receptor affinity, and lipid conjugation in the nasal tissue. The short-term (e.g., effect on linear lower-leg growth rate) and long-term (e.g., effect on height) systemic side effects of INS in patients with AR are determined by these important characteristics. AR is present in up to 75% of patients with asthma, and patients with AR are three times more likely to develop asthma compared with patients without AR. Therefore, the overall increased systemic steroid burden resulting from concomitant use of inhaled corticosteroids (ICS) and INS in adult and pediatric patients with comorbid AR and asthma warrants critical monitoring of systemic side effects. This review evaluates the overall safety of INS in AR and the importance of systemic safety considerations of INS, particularly when coadministered with ICS.