Stem cell factor induces eosinophil activation and degranulation: mediator release and gene array analysis

Eosinophils are effector cells that play an important role in the damage induced by the allergic process by releasing inflammatory mediators and proteolytic factors after activation. Stem cell factor (SCF) is a primary cytokine involved in hematopoiesis and mast cell differentiation, proliferation, and activation. Studies have also indicated that SCF is directly involved in pathogenesis of allergic airway inflammation. In the present study, we examined the ability of SCF to activate murine eosinophils for increased mediator release and up-regulation of chemokines. Initial data demonstrated that eosinophils have significant levels of surface c-kit protein, SCF receptor. SCF-activated eosinophils degranulate and release eosinophil peroxidase and leukotriene C(4) in a dose-dependent manner. In addition, SCF was further shown to induce the release of CC chemokines, RANTES, macrophage-derived chemokine (MDC), macrophage inflammatory protein-1beta (MIP-1beta), and C10 from eosinophils. To identify the extent of SCF-induced activation of eosinophils, we also performed gene array analysis using an array containing 1153 genes related to inflammation, including cytokines and their receptors, growth factors, structural and cytoskeletal genes, signal transduction genes as well as several other classes related to immune/inflammatory responses. The gene analysis indicated that more than 150 genes were significantly up-regulated in eosinophils after SCF stimulation. The gene array results were verified using a quantitative real-time polymerase chain reaction analysis to identify the expression of several chemokine and chemokine receptor genes. Altogether, these studies indicate that SCF is a potent eosinophil degranulator and activator that may play a number of roles during an inflammatory/immune response.     

Maintenance of certification: unilateral cleft lip repair

Cleft lip repair is arguably one of the defining procedures in the field of plastic surgery. The results may be dramatic both visually and emotionally. The variety of techniques of cleft lip repair is well described in the literature, in part because of its inherent difficulty to master. The following article reviews the history of cleft lip repair and attempts to make clear the techniques of the rotation-advancement-type repair.     

Not all obstructive cardiac lesions are created equal: double-chamber right ventricle in pregnancy

Double-chambered right ventricle (DCRV) is a rare form of right ventricular outflow tract (RVOT) obstruction accounting for approximately 1% of patients with congenital heart disease. It consists of an anomalous muscle bundle that divides the right ventricle usually between the sinus (inlet) and the infundibulum (outlet). This division creates a proximal chamber with high pressure and a distal chamber with low pressure. The hemodynamic obstruction of the RVOT is usually an acquired phenomenon, however the substrate for the anomalous muscle bundle is likely congenital. The diagnosis of DCRV should be considered in the young patient with an elevated right ventricular systolic pressure and intracavitary gradient. Echocardiography and cardiac MRI are the principal diagnostic tools for the assessment of DCRV. This entity is often misdiagnosed as pulmonary hypertension in the young patient, and can often go overlooked and untreated for many years. Definitive therapy involves surgical resection of the muscle bundle. This can often be curative and if done in a timely fashion, may prevent right ventricular remodeling. We describe the unique diagnostic dilemma, the course and management of a young adult with DCRV during pregnancy.     

Continuous apex to left ventricle blood flow pattern in hypertrophic cardiomyopathy with apical aneurysm and midventricular obstruction

A 42-year-old female presented with chest pain, noted to have systolic and diastolic murmurs on physical examination and left ventricular hypertrophy on the electrocardiogram. Echocardiography with contrast enhancement revealed hypertrophic cardiomyopathy (HCM) with apical aneurysm and mid left ventricular cavity obstruction. Doppler interrogation showed continuous systolic and diastolic flow from the apex to left ventricle (LV) with a transient deceleration giving rise to a notched pattern. Myocardial ischemia of the apex was demonstrated on adenosine nuclear scintigraphy without epicardial coronary obstruction on angiography. This case demonstrates a novel Doppler pattern with continuous apex to LV flow in HCM in the setting of apical ischemia that may account for the formation of the aneurysm.     

Impact of laminar flow velocity of different acids on enamel calcium loss

Objective

The aim of the study was to evaluate the impact of flow velocity under laminar flow conditions of different acidic solutions on enamel erosion.

Material and methods

A total of 240 bovine enamel specimens were prepared and allocated to 30 groups (n?=?8 each). Samples of 18 groups were superfused in a flow chamber system with laminar flow behavior using 1 ml of citric acid or hydrochloric acid (HCl) of pH 2.0, 2.6 or 3.0. Flow rates in the sample chamber were adjusted to 10, 60 or 100 μl/min. To simulate turbulent flow behavior, samples of six groups were immersed in 1 ml of the respective solution, which was vortexed (15 min, 600 rpm). For simulating non-agitated conditions, specimens of the remaining six groups were immersed in 1 ml of the respective solution without stirring. Calcium in the solutions, released from the enamel samples, was determined using Arsenazo III method.

Results

For acidic solutions of pH 2.6 and 3.0, erosive potential of citric acid was equivalent to that of HCl at a flow of 100 μl/min. The same observation was made for the samples subjected to turbulent conditions at pH 3. At all other conditions, citric acid induced a significantly higher calcium loss than HCl.

Conclusion

It is concluded that under slow laminar flow conditions, flow rate variations lead to higher erosive impact of citric acid compared to hydrochloric acid at pH 2.0, but not at pH?≥?2.6 and increasing laminar flow or turbulent conditions.

Clinical relevance

Erosive enamel dissolution under laminar flow conditions is a complex issue influenced by flow rate and acidic substrate.     

Quantitative X-ray Computed Tomography Peritoneography in Malignant Peritoneal Mesothelioma Patients Receiving Intraperitoneal Chemotherapy

Background

Intraperitoneal chemotherapy is used to treat peritoneal surface-spreading malignancies. We sought to determine whether volume and surface area of the intraperitoneal chemotherapy compartments are associated with overall survival and posttreatment glomerular filtration rate (GFR) in malignant peritoneal mesothelioma (MPM) patients.

Methods

Thirty-eight MPM patients underwent X-ray computed tomography peritoneograms during outpatient intraperitoneal chemotherapy. We calculated volume and surface area of contrast-filled compartments by semiautomated computer algorithm. We tested whether these were associated with overall survival and posttreatment GFR.

Results

Decreased likelihood of mortality was associated with larger surface areas (p = 0.0201) and smaller contrast-filled compartment volumes (p = 0.0341), controlling for age, sex, histologic subtype, and presence of residual disease >0.5 cm postoperatively. Larger volumes were associated with higher posttreatment GFR, controlling for pretreatment GFR, body surface area, surface area, and the interaction between body surface area and volume (p = 0.0167).

Discussion

Computed tomography peritoneography is an appropriate modality to assess for maldistribution of intraperitoneal chemotherapy. In addition to identifying catheter failure and frank loculation, quantitative analysis of the contrast-filled compartment’s surface area and volume may predict overall survival and cisplatin-induced nephrotoxicity. Prospective studies should be undertaken to confirm and extend these findings to other diseases, including advanced ovarian carcinoma.