Application of a topical anesthetic reduces pain-associated parameters during spermatic cord transection in piglet castration using a minimal anesthesia model.

OBJECTIVE: This study assessed the use of a topical anesthetic as a feasible approach to reduce pain during piglet castration using a minimal anesthesia protocol. ANIMALS: 18 male piglets, aged 3-6 days, were included in this study. METHODS: A minimal anesthetic state was induced with isoflurane administered by facemask, with anesthetic depth individually adjusted based on responses to interdigital pinch. To desensitize the scrotal skin, a vapocoolant was applied 3 times. Scrotal incisions were made subsequently and Tri-Solfen (TS) or Placebo (P) was administered in both incisional gaps. After 30 seconds, the spermatic cords were severed followed by a further application of TS/P to both incision edges. Nociception-related variables, such as mean arterial blood pressure (MAP), heart rate (HR), and nocifensive movements, were assessed. RESULTS: Significant differences in MAP changes were assessed between the TS (14 ± 4 mmHg) and the P group (36 ± 8 mmHg) for cutting the spermatic cords. Furthermore, significantly fewer nocifensive movement score points appeared in the TS than in the P group (0; IQR = 0 vs 5; IQR = 6). CLINICAL RELEVANCE: In this anesthesia model, the application of TS after skin incision significantly reduced MAP responses and nocifensive movements with spermatic cord transection compared with the application of P. However, the waiting period between TS-application and spermatic cord transection might limit the benefit of the method in conscious piglets, as pain during castration is reduced but additional stress is caused by the prolonged handling. Furthermore, using a vapocoolant did not provide anesthesia for skin incisions.

Challenges in the transition from resident to attending physician in general internal medicine: a multicenter qualitative study.

BACKGROUND: The attending physician in general internal medicine (GIM) guarantees comprehensive care for persons with complex and/or multiple diseases. Attendings from other medical specialties often report that transitioning from resident to attending is burdensome and stressful. We set out to identify the specific challenges of newly appointed attendings in GIM and identify measures that help residents better prepare to meet these challenges. METHODS: We explored the perceptions of 35 residents, attendings, and department heads in GIM through focus group discussions and semi-structured interviews. We took a thematic approach to qualitatively analyze this data. RESULTS: Our analysis revealed four key challenges: 1) Embracing a holistic, patient centered perspective in a multidisciplinary environment; 2) Decision making under conditions of uncertainty; 3) Balancing the need for patient safety with the need to foster a learning environment for residents; and 4) Taking on a leader's role and orchestrating an interprofessional team of health care professionals. Newly appointed attendings required extensive practical experience to adapt to their new roles. Most attendings did not receive regular, structured, professional coaching during their transition, but those who did found it very helpful. CONCLUSIONS: Newly appointed attending physician in GIM face a number of critical challenges that are in part specific to the field of GIM. Further studies should investigate whether the availability of a mentor as well as conscious assignment of a series of increasingly complex tasks during residency by clinical supervisors will facilitate the transition from resident to attending.

Preclinical investigation of neoatherosclerosis in magnesium-based bioresorbable scaffolds versus thick-strut drug-eluting stents.

AIMS: Neoatherosclerosis is a frequent finding after implantation of permanent metallic stents. Bioresorbable scaffolds (BRS) are considered to reduce the incidence of neoatherosclerosis owing to their dissolution and consequent vascular restoration. The aim of this study was to evaluate the formation of neoatherosclerosis between magnesium-based BRS and thick-strut metallic drug-eluting stents (DES) in a rabbit model of neoatherosclerosis and in proportion to the effect of high-dose statin medication. METHODS AND RESULTS: Fully bioresorbable magnesium scaffolds (BRS, n=45) and thick-strut permanent metallic DES of equivalent geometry and design (n=45) were implanted into the iliac arteries of New Zealand White rabbits (n=45) following endothelial balloon injury and exposure to a cholesterol diet. Endothelialisation was assessed in 12 animals after 35 days using scanning electron microscopy (SEM), showing significantly enhanced re-endothelialisation above struts in the BRS (n=13) compared to DES (n=10). Eleven (11) animals were terminated for baseline assessment after 91 days while the remaining 22 animals were randomised to receive high-dose statin treatment (3 mg/kg) or placebo. BRS-treated vessels showed a significant reduction in foam cell infiltration as a sign of early neoatherosclerosis by histology and OCT when compared to thick-strut DES-treated vessels. Statin treatment resulted in significant reduction of foam cell infiltration in BRS and DES by histology. CONCLUSIONS: Our findings suggest reduced neoatherosclerosis formation in magnesium-based BRS relative to thick-strut DES. High-dose statin treatment may be a promising measure to reduce neoatherosclerosis progression, both on its own and in synergy with site-targeted device-based treatment.

Treatment and Outcomes of Acute Pulmonary Embolism and Deep Venous Thrombosis: The CVRN VTE Study.

BACKGROUND: Few studies describe both inpatient and outpatient treatment and outcomes of patients with acute venous thromboembolism in the United States. METHODS: A multi-institutional cohort of patients diagnosed with confirmed pulmonary embolism or deep venous thrombosis during the years 2004 through 2010 was established from 4 large, US-based integrated health care delivery systems. Computerized databases were accessed and medical records reviewed to collect information on patient demographics, clinical risk factors, initial antithrombotic treatment, and vital status. Multivariable Cox regression models were used to estimate the risk of death at 90 days. RESULTS: The cohort comprised 5497 adults with acute venous thromboembolism. Pulmonary embolism was predominantly managed in the hospital setting (95.0%), while 54.5% of patients with lower extremity thrombosis were treated as outpatients. Anticoagulant treatment differed according to thromboembolism type: 2688 patients (92.8%) with pulmonary embolism and 1625 patients (86.9%) with lower extremity thrombosis were discharged on anticoagulants, compared with 286 patients (80.1%) with upper extremity thrombosis and 69 (54.8%) patients with other thrombosis. While 4.5% of patients died during the index episode, 15.4% died within 90 days. Pulmonary embolism was associated with a higher 90-day death risk than lower extremity thrombosis (adjusted hazard ratio 1.23; 95% confidence interval, 1.04-1.47), as was not being discharged on anticoagulants (adjusted hazard ratio 5.56; 95% confidence interval, 4.76-6.67). CONCLUSIONS: In this multicenter, community-based study of patients with acute venous thromboembolism, anticoagulant treatment and outcomes varied by thromboembolism type. Although case fatality during the acute episode was relatively low, 15.4% of people with thromboembolism died within 90 days of the index diagnosis.

The vasodilating effect of a Hintonia latiflora extract with antidiabetic action.

In the present study, it is shown for the first time that an extract of Hintonia latiflora (HLE) which is used as an antidiabetic herbal medicine, is not only able to decrease blood glucose concentration but additionally exerts a vasodilating effect. Accordingly, this extract might have a positive influence on diabetes-associated dysfunction of blood vessels. The vasodilating effect was demonstrated in vitro in aortic rings of guinea pigs as well as in vivo in rabbits. Aortic rings pre-contracted with noradrenaline (NA) could completely be relaxed by HLE (EC50: 51.98 mg/l). In contrast, potassium-induced contractions were not diminished by HLE. Therefore, it can be suggested that the vasodilating effect of HLE is primarily the result of an inhibition of G protein-induced increase in intracellular calcium and not of a blockade of voltage-operated L-type calcium channels. The neoflavonoid coutareagenin (COU), a constituent of HLE which in part is responsible for the blood glucose-lowering effect of HLE, also relaxed NA-induced contractions of aortic rings (EC50: 32.55 mg/l) and only weakly inhibited potassium-induced contractions. Experiments in aortic rat cells revealed that calcium transients evoked by vasopressin were suppressed by 60 mg/l COU supporting the idea of an inhibition of G protein-induced intracellular calcium release by a constituent of HLE. To study the effect of HLE on vascular tone under in vivo conditions, ultrasound measurements were carried out in conscious rabbits which received a single oral dose of HLE. Under the influence of HLE, a vasodilation combined with a lowering of blood flow velocity could be observed in the abdominal aorta and the common carotid artery. Additionally, a decrease in blood glucose concentration in the HLE group occurred. The combination of a blood glucose-lowering with a vasodilating effect may be helpful for reducing angiopathies, typical long-term complications in patients with diabetes mellitus.

Functional alterations after cardiac sodium-calcium exchanger overexpression in heart failure.

The sodium-calcium exchanger (NCX) is discussed as one of the key proteins involved in heart failure. However, the causal role and the extent to which NCX contributes to contractile dysfunction during heart failure are poorly understood. NCX overexpression was induced by infection with an adenovirus coding for NCX, which coexpressed green fluorescence protein (GFP) (AdNCX) by ex vivo gene transfer to nonfailing and failing rabbit cardiomyocytes. Myocardial gene transfer in rabbits in vivo was achieved by adenoviral delivery via aortic cross-clamping. Peak cell shortening of cardiomyocytes was determined photo-optically. Hemodynamic parameters in vivo were determined by echocardiography (fractional shortening) and tip catheter [maximal first derivative of left ventricular (LV) pressure (dP/dt(max)); maximal negative derivative of LV pressure (-dP/dt(max))]. Peak cell shortening was depressed after NCX gene delivery in isolated nonfailing and in failing cardiomyocytes. In nonfailing rabbits in vivo, basal systolic contractility (fractional shortening and dP/dt(max)) and maximum rate of LV relaxation (-dP/dt(max)) in vivo were largely unaffected after NCX overexpression. However, during heart failure, long-term NCX overexpression over 2 wk significantly improved fractional shortening and dP/dt(max) compared with AdGFP-infected rabbits, both without inotropic stimulation and after beta-adrenergic stimulation with isoproterenol. -dP/dt(max) was also improved after NCX overexpression in the failing rabbits group. These results indicate that short-term effects of NCX overexpression impair contractility of isolated failing and nonfailing rabbit cardiomyocytes. NCX overexpression over 2 wk in vivo does not seem to affect myocardial contractility in nonfailing rabbits. Interestingly, in vivo overexpression of NCX decreased the progression of systolic and diastolic contractile dysfunction and improved beta-adrenoceptor-mediated contractile reserve in heart failure in rabbits in vivo.