Control of the renal artery and vein with the nonabsorbable polymer ligating clip in hand-assisted laparoscopic donor nephrectomy

BACKGROUND: The large and variable size of the renal vein has prompted most surgeons to select linear stapling devices to secure the vein during laparoscopic donor nephrectomy. Although effective, these stapling devices have a potential for misfire. Use of the nonabsorbable polymer ligating (NPL) clip during laparoscopic donor nephrectomy provides increased graft vessel length compared with the stapling device, and the NPL clip has a locking mechanism which may increase security compared with standard titanium clips. The objective of this study was to evaluate the safety and efficacy of the NPL clip for control of the renal artery and vein during hand-assisted laparoscopic donor nephrectomy (HALDN). METHODS: A retrospective chart review of 50 consecutive HALDN patients was conducted where two parallel NPL clips were used to control both the renal artery and vein. Information collected included demographic data, operative and postoperative data, and complications. RESULTS: Mean donor age was 33.4 years and body mass index was 25.8 kg/m2. Mean operative time was 266.0 min, mean hospital stay was 3.2 days, and mean warm ischemia time was 123.3 seconds. There were no transfusions, open conversions, or complications related to use of the NPL clip. A US 16,300 dollars disposable cost savings was seen during this 1-year period alone. CONCLUSIONS: The NPL clip was 100% safe and effective in controlling the renal artery and vein during HALDN, allowed for additional vessel length, and resulted in a disposable cost savings of US 362 dollars per patient.     

Targeting exosites on blood coagulation proteases

The high specificity of blood coagulation proteases has been attributed not only to residues surrounding the active site but also to other surface domains that are involved in recognizing and interacting with macromolecular substrates and inhibitors. Specific blood coagulation inhibitors obtained from exogenous sources such as blood sucking salivary glands and snake venoms have been identified. Some of these inhibitors interact with exosites on coagulation enzymes. Two examples are discussed in this short revision. Bothrojaracin is a snake venom-derived protein that binds to thrombin exosites 1 and 2. Complex formation impairs several exosite-dependent activities of thrombin including fibrinogen cleavage and platelet activation. Bothrojaracin also interacts with proexosite 1 on prothrombin thus decreasing the zymogen activation by the prothrombinase complex (FXa/FVa). Ixolaris is a two Kunitz tick salivary gland inhibitor, that is homologous to tissue factor pathway inhibitor. Recently it was demonstrated that ixolaris binds to heparin-binding exosite of FXa, thus impairing the recognition of prothrombin by the enzyme. In addition, ixolaris interacts with FX possibly through the heparin-binding proexosite. Differently from FX, the ixolaris-FX complex is not recognized as substrate by the intrinsic tenase complex (FIXa/FVIIIa). We conclude that these inhibitors may serve as tools for the study of coagulation exosites as well as prototypes for new anticoagulant drugs.     

O-linked glycosylation and functional incompatibility of porcine von Willebrand factor for human platelet GPIb receptors

BACKGROUND: Xenograft rejection is associated with vascular inflammation, thrombocytopenia and the accelerated consumption of coagulation factors. Primary biological incompatibilities of the xenograft in the regulation of clotting appear to amplify pathological processes associated with rejection. The functional incompatibility of porcine von Willebrand factor (vWF) expressed within the xenograft vasculature may heighten interactions with the primate platelet receptor GPIb, hence augmenting formation of platelet microthrombi and vascular injury. Here, we address the functional impact of O-linked glycosylation of the vWF A1 domain on primate platelet activation. METHODS: Recombinant human or porcine vWF A1-domains were transiently over-expressed in COS-7 cells as FLAG-tagged fusion protein, linked to plasma membranes via GPI anchors. O-linked glycosylation was blocked by the addition of phenyl-alpha-GalNAc2 to cultures. Expressed vWF-A1 domains were characterized utilizing cytofluometric- and Western blot analyses. RESULTS: Cytofluometric analysis confirmed equivalent levels of human and porcine vWF A1-domain expression irrespective of the levels of O-linked glycosylation. Differential glycosylation patterns of vWF-A1 under these conditions were confirmed by Western blot analyses. Native porcine vWF A1-domains had enhanced human platelet activation potential when compared with human recombinant vWF A1. However, the loss of O-linked glycosylation abolished differences in aggregatory responses between human and porcine vWF A1 domains. CONCLUSIONS: Various degrees of O-linked glycosylation of vWF-A1-domains modulate levels of functional interaction with platelet receptor GPIb and consequent platelet aggregation responses in vitro. These data may have implications for outcomes of xenotransplantation. We speculate that alterations in glycosylation of vWF and other adhesion proteins associated with the targeting of the alpha1,3-Gal-epitope in mutant swine may have salutatory effects on the primate platelet activation observed in these xenografts.     

AN EPIDEMIC OF PLEURISY AMONGST MILITARY RECRUITS

An epidemic amongst recruits who presented with acute viral exudative pleural effusion with lymphocytic pleocytosis is analysed. Histologic and bacteriologic proof of tuberculosis was lacking in majority. Most of them recovered without pleural thickening. Overcrowding, inadequate clothing protection, stress and strain of vigorous recruit training could be important precipitating factors. None reported with parenchymal tuberculosis in two year follow up.KEY WORDS: Pleural effussion, Viral     

Atopy influences exhaled nitric oxide levels in adult asthmatics

STUDY OBJECTIVE: To examine whether atopy influences exhaled nitric oxide (NO) levels in adults with established asthma. SETTING: Specialist respiratory unit in a university teaching hospital. PATIENTS: Twenty-eight asthmatics (mean FEV(1), 85.7%) receiving short-acting inhaled bronchodilators and a range of inhaled steroids (0 to 4,000 microg/d). INTERVENTIONS: Subjects were studied on two occasions, 5 to 7 days apart, between September and March. Measurements and results: On the first day, FEV(1), exhaled NO, and histamine challenge were performed. On the second day, exhaled NO, total IgE, and skin-prick testing to six common allergens were conducted. Exhaled NO was measured with the single exhalation method. We found exhaled NO levels to correlate positively with total IgE (r = 0.43, p = 0.02) and number of positive skin-prick tests (p = 0. 002). By contrast, there was no significant correlation between exhaled NO and FEV(1) or the provocative concentration causing a 20% fall in FEV(1). Subanalyses of steroid-treated and steroid-naive patients in this group revealed the same findings. CONCLUSION: Exhaled NO levels in asthmatics correlate more closely with atopy than with bronchial hyperreactivity and lung function.     

Combined stress myocardial CT perfusion and coronary CT angiography as a feasible strategy among patients presenting with acute chest pain to the emergency department

BackgroundA combined approach of myocardial CT perfusion (CTP) with coronary CT angiography (CTA) was shown to have better diagnostic accuracy than coronary CTA alone. However, data on cost benefits and length of stay when compared to other perfusion imaging modalities has not been evaluated. Therefore, we aim to perform a feasibility study to assess direct costs and length of stay of a combined stress CTP/CTA and use SPECT myocardial perfusion imaging (SPECT-MPI) as a benchmark, among chest pain patients at intermediate-risk for acute coronary syndrome (ACS) presenting to the emergency department (ED).MethodsThis is a prospective two-arm clinical trial (NCT02538861) with 43 patients enrolled in stress CTP/CTA arm (General Electric Revolution CT) and 102 in SPECT-MPI arm. Mean age of the study population was 65 ?± ?12 years; 56% were men. We used multivariable linear regression analysis to compare length of stay and direct costs between the two modalities.ResultsOverall, 9 out of the 43 patients (21%) with CTP/CTA testing had an abnormal test. Of these 9 patients, 7 patients underwent invasive coronary angiography and 6 patients were found to have obstructive coronary artery disease. Normal CTP/CTA test was found in 34 patients (79%), who were discharged home and all patients were free of major adverse cardiac events at 30 days. The mean length of stay was significantly shorter by 28% (mean difference: 14.7 ?h; 95% CI: 0.7, 21) among stress CTP/CTA (20 ?h [IQR: 16, 37]) compared to SPECT-MPI (30 ?h [IQR: 19, 44.5]). Mean direct costs were significantly lower by 44% (mean difference: $1535; 95% CI: 987, 2082) among stress CTA/CTP ($1750 [IQR: 1474, 2114] compared to SPECT-MPI ($2837 [IQR: 2491, 3554]).ConclusionCombined stress CTP/CTA is a feasible strategy for evaluation of chest pain patients presenting to ED at intermediate-risk for ACS and has the potential to lead to shorter length of stay and lower direct costs.