Molecular and histological effects of MR-guided pulsed focused ultrasound to the rat heart

Background

Image-guided high intensity focused ultrasound has been used as an extracorporeal cardiac pacing tool and to enhance homing of stem cells to targeted tissues. However, molecular changes in the myocardium after sonication have not been widely investigated. Magnetic-resonance (MR)-guided pulsed focused ultrasound (pFUS) was targeted to the rat myocardium over a range of pressures and the microenvironmental and histological effects were evaluated over time.

Methods

Eight-to-ten-week-old Sprague–Dawley rats received T2-weighted MR images to target pFUS to the left ventricular and septum without cardiac or respiratory gating. Rats were sonicated through the thoracic wall at peak negative pressures (PNP) from 1 to 8 MPa at a center frequency of 1 MHz, 10 ms pulse duration and 1 Hz pulse repetition frequency for 100 pulses per focal target. Following pFUS, myocardium was harvested over 24 h and subjected to imaging, proteomic, and histological measurements.

Results

pFUS to the myocardium increased expression of cytokines, chemokines, and trophic factors characterized by an initial increase in tumor necrosis factor (TNF)-α followed by increases in pro- and anti-inflammatory factors that returned to baseline by 24 h. Immediately after pFUS, there was a transient (< 1 h) increase in N-terminal pro b-type natriuretic peptide (NT-proBNP) without elevation of other cardiac injury markers. A relationship between PNP and expression of TNF-α and NT-proBNP was observed with significant changes (p < 0.05 ANOVA) ≥ 4 MPa compared to untreated controls. Contrast-enhanced ex vivo T1-weighted MRI revealed vascular leakage in sonicated myocardium that was accompanied by the presence of albumin upon immunohistochemistry. Histology revealed infiltration of neutrophils and macrophages without morphological myofibril changes in sonicated tissue accompanied by pulmonary hemorrhage at PNP > 4 MPa.

Conclusions

MR-guided pFUS to myocardium induced transient proteomic and histological changes. The temporal proteomic changes in the myocardium indicate a short-lived sterile inflammatory response consistent with ischemia or contusion. Further study of myocardial function and strain is needed to determine if pFUS could be developed as an experimental model of cardiac injury and chest trauma.

     

Axillary nerve course and position in the fetal period: An anatomic dissection study for surgical practice

Objectives:

To examine the fetal axillary nerve to reveal and compare its morphometric features within the second and third trimester.

Methods:

This study was conducted at the Anatomy Department, School of Medicine, Mersin University, Mersin, Turkey. Thirty-five fetal shoulders were studied to provide anatomic data and to describe its position with regard to certain landmarks around the shoulder.

Results:

The shortest distance between the axillary nerve and the glenoid labrum was found 2.27 mm and 2.89 mm in the second and third trimester fetuses, respectively. The shortest distances between the anterior and posterior acromial tips and the axillary nerve were also measured and were used with arm length measurements to define the anterior and posterior indexes.

Conclusion:

The indexes show that the distance between the axillary nerve and the anterior/posterior acromial tips are approximately one-fourth of the arm length in both the second and third trimester fetuses. The data presented in this study will be of use to surgeons, particularly to pediatric and orthopedic surgeons who will undertake surgical procedures in the axilla and arm in the newborn or early childhood.There is detailed knowledge regarding the morphological features of the axillary nerve in adults, however, it in the fetal period we encountered no information. Brachial plexus injuries have been reported with a rate of 0.38-2.6 per thousand live births. Shenaq et al1 mentioned that the diagnosis, observation, and therapy are the initial approaches to these injuries, and should be initiated immediately. They also stated that early surgical intervention is essential to maximizing the long-term improvements in selected patients by helping to prevent residual growth deformities and underdevelopment of the affected limbs. The surgical treatment options include the reconstruction and neurotization.2 For the axillary nerve injuries, for example in case of C5-C6 avulsion, in which the upper roots have been avulsed from the spinal cord, and the clinical picture is that of a classic Erb palsy, they preferred to use neurotization technique. In this type of avulsion, the upper roots are not available as donors, and the C7-T1 roots are uninvolved. So, the suprascapular nerve is neurotized by the ipsilateral spinal accessory nerve, and the axillary nerve is neurotized by redundant branches to the triceps to ideally restore shoulder and elbow function. The thoracodorsal or the subscapular branches can also be neurotized to the axillary nerve to provide better shoulder function. Thus, anatomical details of the axillary nerve in fetal period become essential for such operations. We carried out this study to evaluate these parameters regarding the axillary nerve anatomy, which may be helpful to surgeons in certain conditions, such as end-to-side neurorrhaphy in brachial plexus reconstruction, neurotization, proximal humeral fracture repair, and shoulder dislocation treatment in the early childhood.     

Issues influencing development of the Canadian Cardiovascular Information Network

The 1995 Consensus Conference of the Canadian Cardiovascular Society on "Indications for and Access to Revascularization" recommended that Canadian centres with invasive cardiovascular facilities should participate in a national observational database that monitors the selection of patients, as well as evaluate outcomes. The Canadian Cardiovascular Society, the Heart and Stroke Foundation of Canada, and Health Canada with IBM as a partner, initiated a process to identify factors influencing the development of the Canadian Cardiovascular Information Network. IBM's "Business Discovery Methodology" was adapted for health care. Structured interviews with representatives of health organizations, cardiovascular databases and research institutes were conducted across Canada, followed by a workshop to identify goals, issues and challenges. Participants identified goals for a cardiovascular database (eg, evidence-based decision-making), project related issues (eg, respecting the integrity of existing databases) and health care related issues (eg, cardiac waiting lists). Challenges included initial mistrust between representatives of provincial cardiovascular databases and national agencies, and a lack of sustained funding. A Project Team was formed to address 'cardiac waiting lists'. Analysis of Alberta and Ontario data identified differences in definitions, such as when the waiting time for bypass surgery began, that impeded detailed comparisons. Development of a centralized national database was not feasible at this time for political, technical and financial reasons. However, provincial cardiovascular database representatives agreed to work together and to share aggregate data and analyses. A first step toward developing a national surveillance system for cardiovascular services will be achieving consensus about standardizing data definitions. This process will require sustained funding.     

Ductal and acinar differentiation in pancreatic endocrine tumors

Rare pancreatic endocrine tumors consisting of both exocrine and endocrine components have been reported sporadically. We investigated the ductal and acinar differentiation in pancreatic endocrine tumors. In immunohistochemical studies of 28 pancreatic endocrine tumors, staining with anti-carcinoembryonic antigen (CEA) or CA19-9 antibody indicated ductal differentiation, while staining with anti-amylase or anti-trypsin antibody indicated acinar differentiation. K-ras gene mutations and p53 gene alterations also were studied. Ten tumors were immunoreactive for CEA or CA19-9. Five tumors diffusely immunoreactive for CEA or CA19-9, in addition to endocrine markers, were diagnosed as duct–endocrine cell tumors of the pancreas. Two tumors diffusely immunoreactive for CEA or CA19-9 and also for pancreaticogut hormones as well as endocrine markers were diagnosed as duct–acinar–endocrine cell tumors. These tumors showed uniform histologic features and synchronous ductal, acinar, and endocrine differentiation, distinct from the coexisting different cellular populations seen in collision tumors. All tumors were malignant. These duct–endocrine cell tumors or duct–acinar–endocrine cell tumors of the pancreas may be derived from a stem cell that retains the capability of expressing either an exocrine or endocrine phenotype. Only one K-ras gene mutation and no p53 gene alterations were detected in these tumors, which suggests that they constitute an entity with a different origin than ductal carcinomas.     

Rescue angioplasty or repeat fibrinolysis after failed fibrinolytic therapy for ST-segment myocardial infarction: a meta-analysis of randomized trials.

OBJECTIVES: We sought to best estimate the benefits and risks associated with rescue percutaneous coronary intervention (PCI) and repeat fibrinolytic therapy as compared with conservative management in patients with failed fibrinolytic therapy for ST-segment myocardial infarction (STEMI). BACKGROUND: Fibrinolytic therapy is the most common treatment for STEMI; however, the best therapy in patients who fail to achieve reperfusion after fibrinolytic therapy remains uncertain. METHODS: We performed a meta-analysis of randomized trials using a fixed-effects model. We included 8 trials enrolling 1,177 patients with follow-up duration ranging from hospital discharge to 6 months. RESULTS: Rescue PCI was associated with no significant reduction in all-cause mortality (relative risk [RR] 0.69; 95% confidence interval [CI] 0.46 to 1.05), but was associated with significant risk reductions in heart failure (RR 0.73; 95% CI 0.54 to 1.00) and reinfarction (RR 0.58; 95% CI 0.35 to 0.97) when compared with conservative treatment. Rescue PCI was associated with an increased risk of stroke (RR 4.98; 95% CI 1.10 to 22.5) and minor bleeding (RR 4.58; 95% CI 2.46 to 8.55). Repeat fibrinolytic therapy was not associated with significant improvements in all-cause mortality (RR 0.68; 95% CI 0.41 to 1.14) or reinfarction (RR 1.79; 95% CI 0.92 to 3.48), but was associated with an increased risk for minor bleeding (RR 1.84; 95% CI 1.06 to 3.18). CONCLUSIONS: Rescue PCI is associated with improved clinical outcomes for STEMI patients after failed fibrinolytic therapy, but these benefits must be interpreted in the context of potential risks. On the other hand, repeat fibrinolytic therapy is not associated with significant clinical improvement and may be associated with increased harm.