Expression of cyclooxygenase-2 in osteosarcoma of bone.

Several studies indicate that cyclooxygenase-2 (COX-2) is overexpressed in human malignancies, where it produces high levels of prostaglandins and contributes to tumor growth. In this study we have analyzed the expression of COX-2 in a series of 48 skeletal osteosarcomas of different subtypes by immunohistochemistry. In addition, we examined the effects of the specific COX-2 inhibitor Celecoxib on the growth of the human osteosarcoma cell line SaOS-2. Immunoreactivity for COX-2 was observed in 39 out of 48 tumors (81.2%), 30 (76.9%) of which showed a moderate or diffuse immunostaining. Considering the group of 42 primary osteosarcomas, COX-2 immunoreactivity was significantly higher in high grade osteosarcomas, where moderate or diffuse expression was detected in 23 out of 32 cases (71.8%), than in low grade osteosarcomas, where moderate or diffuse expression was detected in 2 out of 10 cases (20%) (P = 0.008, Fisher exact test). In addition, low COX-2 expression was always associated with a good response to chemotherapy (5 out of 5 cases), whereas moderate or diffuse COX-2 expression was associated with a good response in 11 out of 20 cases (55%) (P = 0.12, Fisher exact test). In SaOS-2 osteosarcoma cells, which express COX-2, treatment with Celecoxib determined inhibition of cell proliferation and induction of apoptosis. These results indicate that COX-2 is expressed at high levels in high grade osteosarcomas and support the use of COX-2 inhibitors to improve both the tumor response to chemotherapy and the outcome of osteosarcoma patients.     

Effects of acute angiotensin-converting enzyme inhibition on diastolic ventricular interaction in the dilated heart

BACKGROUND: The normal and dilated heart behaves as a single functional unit during preload reduction: volume unloading in the setting of diastolic ventricular interaction allows for increased left ventricular (LV) filling. HYPOTHESIS: We hypothesized that reduction of venous return induced by a physiologic stimulus (tilting) or by acute angiotensin-converting enzyme (ACE) inhibitors in dilated heart is likely to have a marked and similar effect on ventricular chamber geometry and filling. This study was designed to assess how the normal and dilated heart adapts to preload reduction. METHODS: Twenty normal subjects and 20 patients with moderate heart failure due to dilated cardiomyopathy were studied with two-dimensional and Doppler echocardiography in supine position (B) and after 40 degrees of head-up tilting (T). The following day, patients repeated supine (C) and tilting test (TC) after administration of captopril (25 mg s.l.). Right ventricular (RV) and LV dimensions, LV geometry, and tricuspid, mitral, and pulmonary venous flow patterns were recorded at each step of the study. RESULTS: In the two groups, T was associated with reduction of RV area and LV volumes; C and TC produced a similar effect on RV and LV. Changes in LV septal-lateral diameter and anterior-posterior diameter were different at each step of the study: during T (both groups) and after C and TC, the septallateral diameter increased slightly while the anterior-posterior diameter decreased. During T, mitral and tricuspid peak flow velocities decreased, peak late velocities were unchanged, and the deceleration time of mitral flow increased; the systolic forward flow of pulmonary venous flow decreased, the diastolic forward flow did not change, and the difference in duration between reverse pulmonary flow and mitral peak late flow decreased: C and CT induced similar changes. CONCLUSION: Preload reduction induced by tilting or by ACE inhibitors induces profound and similar effects on LV and RV dimensions, LV geometry, and biventricular filling. Reduction of RV dimension is associated with adaptation of LV geometry and decrease of LV diastolic pressure, which facilitates LV filling and pulmonary venous drainage: ACE inhibition associated with tilting exerts an additional effect on these changes. These data confirm the role of ventricular interaction in modulating LV filling in heart failure.     

2D shear wave elastography in evaluation of prognostic factors in breast cancer

Purpose

To evaluate the reproducibility of the 2D shear wave elastography (2D-SWE) method and to identify the prognostic factors of breast lesions.

Methods

In this prospective study, 44 female patients were consecutively included from January 2020 to September 2021. All patients showing visible masses at B-mode ultrasound underwent to clinical evaluation, followed by qualitative and quantitative 2D-SWE by two different operators with over 15-year and 2-year experience, respectively. Subsequently, patients underwent to surgical treatment after core needle biopsy. Reproducibility of qualitative and quantitative 2D-SWE was evaluated by Cohen’s kappa and intraclass correlation coefficient (ICC). Clinical, imaging, and histopathological data and 2D-SWE evaluations were analysed with Spearman's rank correlation test.

Results

The mean age of the patients was 55 years?±?12. The mean histological and ultrasound tumour size of were 23.1 mm?±?13.2 and 17.2 mm?±?10.2, respectively. The interobserver agreement showed a good reproducibility limited to the qualitative evaluation colour maps (Cohen’s kappa?=?0.603) and to the quantitative evaluation E ratio (ICC?=?0.771). Correlation analysis between the ultrasound and 2D-SWE values and the clinical-pathological parameters showed a significant relationship between E ratio and Elston–Ellis grading (P?<?0.030) and between tumour size and Elston–Ellis grading (P?<?0.041).

Conclusion

The 2D-SWE has shown good reproducibility among operators with different experience. It could be a promising tool in the evaluation of some prognostic factors in ultrasound visible breast cancer.

     

Surgery for drug‐resistant tuberous sclerosis complex‐associated epilepsy: who,when, and what

Objective: Tuberous sclerosis complex (TSC) is a multisystem genetic disorder associated with refractory early‐onset epilepsy. Current evidence supports surgery as the intervention most likely to achieve long‐term seizure freedom, but no specific guidelines are available on TSC pre‐surgical workup. This critical review assesses which TSC patients are suitable for surgical treatment, when pre‐surgical evaluation should start, and what degree of surgical resection is optimal for postsurgical outcome. Methods: We searched for publications from 2000 to 2020 in Pubmed and Embase using the terms “tuberous sclerosis,” “epilepsy,” and “epilepsy surgery”. To evaluate postsurgical seizure outcome, we selected only studies with at least one year of follow‐up. Results: Overall, we collected data on 1,026 patients from 34 studies. Age at surgery ranged from one month to 54 years. Mean age at surgery was 8.41 years. Of the diagnostic non‐invasive pre‐surgical tools, MRI and video‐EEG were considered most appropriate. Promising data for epileptogenic tuber detection is provided from invasive SEEG studies. Data on surgery and related outcome were available for 769 patients. Seizure freedom was seen in 64.4% of patients who underwent tuberectomy, 68.9% treated with lobectomy and 65.1% with multilobar resection. The most effective surgical approach was lobectomy, even though more recently tuberectomy associated with the resection of the perituberal area seems to be the best approach to reach seizure freedom. Published postsurgical seizure freedom rates in patients with TSC were between 65% and 75%, but reduced to 48%‐57% over longer follow‐up periods. Early surgery might positively affect neurodevelopmental trajectory in some patients, even though data on cognitive outcome are still to be confirmed with longitudinal studies. Significance: Considering the strong correlation between epilepsy duration and neurocognitive outcome, all patients with TSC ought to be referred early to a dedicated epilepsy centre for individually tailored pre‐surgical evaluation by a multi‐disciplinary epilepsy surgery team.     

D-Optimal Design in the Development of Rheologically Improved In Situ Forming Ophthalmic Gel

In situ forming ophthalmic gels need to be fine tuned considering all the biopharmaceutical challenges of the front of the eye in order to increase drug residence time at the application site resulting in its improved bioavailability and efficacy. The aim of this study was to develop in situ forming ophthalmic poloxamer P407/poloxamer P188/chitosan gel fine tuned in terms of polymer content, temperature of gelation, and viscosity. Minimizing the total polymer content while retaining the advantageous rheological properties has been achieved by means of D-optimal statistical design. The optimal in situ forming gel was selected based on minimal polymer content (P407, P188, and chitosan concentration of 14.2%, 1.7%, and 0.25% w/w, respectively), favorable rheological characteristics, and in vitro resistance to tear dilution. The optimal in situ forming gel was proved to be robust against entrapment of active pharmaceutical ingredients making it a suitable platform for ophthalmic delivery of active pharmaceutical ingredients with diverse physicochemical properties.     

Sustained cardiac diastolic changes elicited by ultrafiltration in patients with moderate congestive heart failure: pathophysiological correlates.

OBJECTIVE--To investigate the pathophysiological (cardiac function and physical performance) significance of clinically silent interstitial lung water accumulation in patients with moderate heart failure; to use isolated ultrafiltration as a means of extravascular fluid reabsorption. DESIGN--Echocardiographic, Doppler, chest x-ray evaluations, and cardiopulmonary tests at baseline, soon after ultrafiltration (veno venous extracorporeal circuit), and four days, one month, and three months later. SETTING--University institute of cardiology. SUBJECTS--24 patients with heart failure due to idiopathic dilated cardiomyopathy or ischaemic myocardial disease with sinus rhythm and ejection fraction less than 35%. Twelve were randomised to ultrafiltration and 12 were taken as controls. MAIN OUTCOME MEASURES--Left ventricular systolic function (from ultrasonography); Doppler evaluation of mitral, tricuspid, and aortic flow and echo-Doppler determination of cardiac output; radiological score of extravascular lung water; right and left ventricular filling pressures; oxygen consumption at peak exercise and exercise tolerance time in cardiopulmonary tests. RESULTS--Soon after ultrafiltration (1976 (760) ml of fluid removed) the following was observed: a reduction in radiological score of extravascular lung water (from 15(1) to 9(1)) and of right (from 7.1 (2.3) to 2.3 (1.7) mm Hg) and left (from 17.6 (8.8) to 9.5 (6.4) mm Hg) ventricular filling pressures; an increase in oxygen consumption at peak exercise (from 15.8 (3.3) to 17.6 (2) ml/min/kg) and of tolerance time (from 444 (138) to 508 (134) s); a slight decrease in atrial and ventricular dimensions; no changes in the systolic function of the left ventricle; a reduction of the early to late filling ratio in both ventricles (mitral valve from 2 (2) to 1.1 (1.1)); (tricuspid valve from 1.3 (1.3) to 0.69 (0.18)) and an increase in the deceleration time of mitral and tricuspid flow, reflecting a redistribution of filling to late diastole. Variations in the ventricular filling pattern, lung water content, and functional performance persisted for three months in all cases. None of these changes was detected in the control group. CONCLUSIONS--Reduction of interstitial lung water was probably the mechanism whereby ultrafiltration modified the pattern of filling of the two ventricles and improved functional performance.     

The influence of diastolic and systolic function on exercise performance in heart failure due to dilated cardiomyopathy or ischemic heart disease

BACKGROUND: Peripheral adaptations and ventricular abnormalities influence physical performance in chronic heart failure. However, the role of the heart in determining exercise capacity has not been completely elucidated. AIMS: To define cardiac determinants of exercise capacity in patients with dilated cardiomyopathy. METHODS: In 101 patients with heart failure (NYHA class II-III) due to primary or ischemic dilated cardiomyopathy we measured peak exercise oxygen consumption (Pvo2), left ventricular ejection fraction (EF), left and right atrial and ventricular cavity dimensions, mitral and tricuspid flows. Patients were subdivided in class A (Pvo2 > 20 ml/min per kg; n = 44), class B (Pvo2 16-20 ml/min per kg; n = 42) and class C (Pvo2 < 16 ml/min per kg; n = 15). RESULTS: Left ventricular diastolic and systolic dimensions, left atrial diameter, right atrial and ventricular areas were greater in class C than in class B and A; EF was lower in class C than in the other two classes; mitral peak flow velocity at early diastole (PFVE) and the ratio between early and late peak flow velocity (PFVE/PFVA) were higher in class C; mitral and tricuspid deceleration time (DT) in class B and A significantly exceeded those in class C. Peak vo2 was correlated with left and right ventricular dimensions, left atrial diameter, EF, mitral PFVE and PFVE/PFVA, mitral and tricuspid DT. Left ventricular EF, DT of the mitral valve and left ventricular diastolic diameter were independent predictors of peak vo2 at multivariate analysis. CONCLUSIONS: In patients with dilated cardiomyopathy Pvo2 is related to left and right ventricular dimensions, left and right ventricular filling pattern and EF. Both systolic and diastolic dysfunction influence functional capacity.     

Determination of textile dyes in organs of Oncorhynchus mykiss W. after in vitro exposure

The quantitative determination in organs of Oncorhynchus mykiss W. of a premetallized dye (C.I. Acid Violet 66) and the azoic base (C.I. Acid Red 217), used in wool dyeing, is studied in this paper. UV-VIS Spectrophotometry was used for the chromatic quantification and atomic absorption spectrophotometry for the detection of the metal. The method described here is as satisfactory for the detection of some commercial dyes as the methods developed by ETAD (Ecological and Toxicological Association of the Dyestuffs Manufacturing Industry).