Stromal interleukin-1 expression in the cornea after haze-associated injury

The purpose of this study was to determine whether myofibroblasts or other cells in the stroma in the cornea produce interleukin (IL)-1 alpha or IL-1 beta that could modulate myofibroblast viability in corneas with haze after photorefractive keratectomy (PRK). Twenty-four female rabbits had haze-generating PRK for 9 diopters of myopia and were sacrificed at 1 week, 2 weeks, 3 weeks or 4 weeks after surgery. Corneal rims were removed, frozen in OCT at -80 degrees C, and analyzed by immunocytochemistry using primary antibodies to IL-1 alpha, IL-1 beta and alpha smooth muscle actin (SMA). Double immunostaining was performed for the co-localization of SMA with IL-1 alpha or IL-1 beta. Central dense haze and peripheral slight haze regions of each cornea were analyzed. SMA+ cells that expressed IL-1 alpha protein were detected in both regions of the corneas at most time points following PRK. However, in the haze region at the 1,3 and 4 week time points, significantly more (p < 0.01) SMA cells did not express IL-1 alpha. Also, in the haze region at all three time points, significantly more (p < 0.01) SMA- cells than SMA+ cells expressed interleukin-1 alpha protein. IL-1 beta expression patterns in SMA+ and SMA- stromal cells was similar to that of IL-1 alpha after PRK. Previous studies have demonstrated that IL-1 alpha or IL-1 beta triggers myofibroblast apoptosis in vitro, depending on the available concentration of apoptosis-suppressive TGFO. This study demonstrates that SMA- cells such as corneal fibroblasts, keratocytes, or inflammatory cells may produce IL-1 alpha and/or IL-1 beta that could act in paracrine fashion to regulate myofibroblast apoptosis-especially in the region where there is haze in the cornea after PRK was performed and SMA+ myofibroblasts are present at higher density. However, some SMA+ myofibroblasts themselves produce IL-1 alpha and/or IL-1 beta, suggesting that myofibroblast viability could also be regulated via autocrine mechanisms. (C) 2010 Elsevier Ltd. All rights reserved.

Reticular angiomatoid ""malignant"" fibrous histiocytoma-a case report with cytogenetics and molecular genetic analyses

Angiomatoid ""malignant"" fibrous histiocytoma is a rare sarcoma of low malignant potential that occurs most commonly in the extremities of children and young adults. Herein, we present a case of angiomatoid malignant fibrous histiocytoma with unusual histologic features arising in the mediastinum of an 80-year-old man. The tumor exhibited a reticular growth pattern and myxoid stroma. The tumor cells expressed epithelial membrane antigen and desmin. Cytogenetic analysis revealed the translocation t(2;22)(q33;q12). Molecular genetic analysis confirmed the rearrangement of the EWSR1 locus and the presence of the EWSR1/CREB1 fusion. This report expands the clinicopathologic spectrum of angiomatoid malignant fibrous histiocytoma and underscores the value of integrating morphologic, immunophenotypic, and molecular findings in the identification of its unusual morphologic variants. (C) 2011 Elsevier Inc. All rights reserved.

Comparison of Different Spectral Domain Optical Coherence Tomography Scanning Areas for Glaucoma Diagnosis

Purpose: To evaluate retinal nerve fiber layer (RNFL), optic nerve head (ONH), and macular thickness measurements for glaucoma detection using the RTVue spectral domain optical coherence tomograph. Design: Diagnostic, case-control study. Participants: One hundred forty eyes of 106 glaucoma patients and 74 eyes of 40 healthy subjects from the Diagnostic Innovations in Glaucoma Study (DIGS). Methods: All patients underwent ocular imaging with the commercially available RTVue. Optic nerve head, RNFL thickness, and macular thickness scans were obtained during the same visit. Receiver operating characteristic (ROC) curves and sensitivities at fixed specificities (80% and 95%) were calculated for each parameter. Main Outcome Measures: Areas under the ROC curves (AUC) and sensitivities at fixed specificities of 80% and 95%. Results: The AUC for the RNFL parameter with best performance, inferior quadrant thickness, was significantly higher than that of the best-performing ONH parameter, inferior rim area (0.884 vs 0.812, respectively; P = 0.04). There was no difference between ROC curve areas of the best RNFL thickness parameters and the best inner macular thickness measurement, ganglion cell complex root mean square (ROC curve area = 0.870). Conclusions: The RTVue RNFL and inner retinal macular thickness measurements had good ability to detect eyes with glaucomatous visual field loss and performed significantly better than ONH parameters.

Chronic Rhinosinusitis in Allergic Asthmatic Patients: Radiography Versus Low-Dose Computed Tomography Evaluation

Objective. Chronic rhinosinusitis (CRS) is a risk factor for asthma exacerbations and is associated with greater clinical severity. Discrepancies may exist between CRS clinical diagnosis and data from paranasal sinus (PS) X-ray or computed tomography (CT) scans. The objective was to compare PS involvement using low-dose CT and plain X-ray in allergic asthmatic patients with rhinitis. Methods. Patients underwent PS radiography in the frontal and mentonian positions and low-dose CT consisting of six to eight coronal scans performed on the central region of the sphenoidal, ethmoidal, maxillary, and frontal sinuses. Possible results for each sinus were a normal aspect or the presence of mucosal thickening, opacification, and/or air-fluid level. Results. Eighty-five (93.4%) of 91 study patients had radiological changes on radiography or CT. In only six (6.6%) were both tests normal. The maxillary was the most involved sinus by both methods. Simultaneous PS abnormalities were observed in 40.5% on X-ray and 56.7% on CT. For the frontal, ethmoidal, and sphenoidal sinuses, the proportion of normal results differed significantly between X-ray and CT: 80.2% versus 89%, 76.9% versus 63.7% and 96.7% versus 70.3%, respectively (p <.05). Agreement was over 70% for the maxillary and frontal sinuses. CT also provided a better diagnosis of air-fluid level changes than X-ray. Conclusions. Low-dose CT significantly showed larger number of normal PS results and diagnosed more severe PS lesions. As the determination of true sinus severity lesion impacts in asthma control, low-dose CT may replace PS plain X-ray and conventional CT to support better clinical decisions.

Predictive factors for the development of visual loss in patients with pituitary macroadenomas and for visual recovery after optic pathway decompression

Objective: To investigate clinical and MRI findings that are predictive of both visual loss in patients with pituitary adenomas and visual recovery after treatment. Design: Cohort study. Participants: Thirty patients (60 eyes) with pituitary adenoma. Methods: Patients underwent neuro-ophthalmic examination and MRI before and after optic chiasm decompression. Visual field (VF) was assessed using the mean deviation in standard automated perimetry (SAP) and temporal mean defect, the average of 22 temporal values of the total deviation plot. Tumour size was measured on sagittal and coronal cuts. Results: Visual loss was found in 47 eyes; 35 had optic atrophy (subtle in 9, moderate in 14, and severe in 12). Before treatment, the average SAP mean deviation and temporal mean defect were -11.78 (SD 8.56) dB and -18.66 (SD 11.20) dB, respectively. The chiasm was 17.3 (SD 6.2, range 10-34) mm above the reference line on the sagittal and 21.8 (SD 8.3, range 12-39) mm on the coronal images. Tumour size correlated with the severity of VF defect. VF improvement occurred in 80% of eyes after treatment. The degree of optic atrophy, visual loss, and tumour size were significantly associated with improvement after treatment. Conclusions: The best predictive factor for visual loss was tumour size, and factors related to visual recovery were the degree of optic atrophy, the severity of VF defect, and the tumour size. Diagnosing pituitary adenomas before optic atrophy becomes severe may be related to a better prognosis in such patients.

DOG1 for the Diagnosis of Gastrointestinal Stromal Tumor (GIST): Comparison Between 2 Different Antibodies

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Discovered on GIST-1 (DOG1) is a recently described protein expressed in GISTs irrespective of mutation status. The aim of this study was to investigate the immunohistochemical expression of DOG1 using 2 different monoclonal antibodies (DOG1.1 and the commercially available K9 antibody) in 668 GIST cases and to compare the results with the expression of KIT. DOG1 and KIT expression also were studied in most human normal tissues and several nonmesenchymal and mesenchymal tumors other than GIST. KIT was expressed in 643 (96.3%) GISTs. DOG1.1 and K9 were positive in 538 (80.5%) and 642 (96.1%) GIST cases, respectively. In 25 (3.7%) KIT-negative GIST cases, DOG1 was expressed in 5 (20.0%) and 19 (76.0%) using DOG1.1 and K9 antibodies, respectively. Only 0.9% of GISTs were negative for KIT, DOG1.1, and K9. Most normal human tissues did not reveal KIT and DOG1 expression. DOG1.1 was positive in only 2 of 57 synovial sarcomas and 1 of 61 soft tissue leiomyosarcomas. K9 was positive in 5 of 57 synovial sarcomas, 1 of 14 angiosarcomas, 1 of 61 soft tissue leiomyosarcomas, 3 of 4 adenoid cystic carcinomas of the head and neck, and in myoepithelial cells of 9 of 11. broadenomas of the breast. In conclusion, the commercially available K9 is of great utility for the diagnosis of most KIT-negative GISTs, and the combination of both KIT and K9 antibody in a panel of immunohistochemistry can define the diagnosis of GIST in more than 99% of cases.

Anterior genu corpus callosum and impulsivity in suicidal patients with bipolar disorder

Suicidality is a life-threatening symptom in patients with bipolar disorder (BD). Impulsivity and mood instability are associated with suicidality in mood disorders. Evidence suggests that gray and white matter abnormalities are linked with impulsivity in mood disorders, but little is known about the association between corpus callosum (CC) and impulsivity in BID. We examined the relationship between CC areas, impulsivity and suicidality in BID patients. We studied 10 female BD patients with a history of suicide attempt (mean +/- SD age 36.2 +/- 10.1 years), 10 female BD patients without suicide attempt history (44.2 +/- 12.5 years) and 27 female healthy subjects (36.9 +/- 13.8 years). Impulsivity was evaluated by the Barratt Impulsivity Scale (BIS). We traced MR images to measure the areas of the CC genu, anterior body, posterior body, isthmus and splenium. The genu was divided into anterior, middle and posterior regions. The suicidal and non-suicidal BID patients had significantly higher BIS total, attention and non-planning scores than the healthy subjects (ps < 0.01), and the suicidal BID patients had significantly higher BIS motor scores than the non-suicidal BD and healthy subjects (ps < 0.01). There were no significant differences among the three groups on any regional CC areas, although the suicidal BD patients had the smallest areas. The suicidal BD patients showed a significant inverse correlation between anterior genu area and the BIS total (r = -0.75, p = 0.04), motor (r = -0.79, p = 0.02) and non-planning scores (r = -0.79, p = 0.02). These correlations were not found in the non-suicidal BID patients or healthy subjects. The results suggest that the anterior medial frontal region may be involved in the pathophysiology of impulsive and suicidal behaviors in BD. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Induction and maintenance of in vivo ventricular fibrillation in rabbits

Aim: To provide new sustainable in vivo models of ventricular fibrillation in rabbits. Methods: New Zealand rabbits were submitted to anaesthesia and mechanical ventilation. after which ventricular fibrillation was induced through electrical stimulation (for 2 min at 100 Hz, with 2-ms pulses, 10 mA. and 10V) directly to the heart. To that end, the animals were divided into two groups: right ventricle (n = 11) and left ventricle (n = 11). In group right ventricle, the thoracic cavity was exposed, and a catheter was introduced into the right ventricle via the right jugular vein. in group left ventricle, the thorax remained closed, and the catheter was introduced into the left ventricle via the left common carotid artery (cervical access). Results: Sustained ventricular fibrillation was achieved in 100% of group right ventricle rabbits (n = 11 and in 82% of group left ventricle rabbits (n = 9). Conclusion: Both models proved appropriate for achieving sustained ventricular fibrillation. However, in view of the invasiveness of the procedure adopted in group right ventricle, the experimental conditions used in group left ventricle seemed more physiological and more effective in inducing sustained ventricular fibrillation. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Reprint of ""Dynamics of the expression of intermediate filaments vimentin and desmin during myofibroblast differentiation after corneal injury""

Previous studies have suggested that abnormal corneal wound healing in patients after photorefractive keratectomy (PRK) is associated with the appearance of myofibroblasts in the stroma between two and four weeks after surgery. The purpose of this study was to examine potential myofibroblast progenitor cells that might express other filament markers prior to completion of the differentiation pathway that yields alpha-smooth muscle actin (SMA)-expressing myofibroblasts associated with haze localized beneath the epithelial basement membrane after PRK. Twenty-four female rabbits that had -9 diopter PRK were sacrificed at 1 week, 2 weeks, 3 weeks or 4 weeks after surgery. Corneal rims were collected, frozen at -80 degrees C, and analyzed by immunocytochemistry using anti-vimentin, anti-desmin, and anti-SMA antibodies. Double immunostaining was performed for the co-localization of SMA with vimentin or desmin with SMA. An increase in vimentin expression in stromal cells is noted as early as 1 week after PRK in the rabbit cornea. As the healing response continues at two or three weeks after surgery, many stromal cells expressing vimentin also begin to express desmin and SMA. By 4 weeks after the surgery most, if not all, myofibroblasts express vimentin, desmin and SMA. Generalized least squares regression analysis showed that there was strong evidence that each of the marker groups differed in expression over time compared to the other two (p < 0.01). Intermediate filaments - vimentin and desmin co-exist in myofibroblasts along with SMA and may play an important role in corneal remodeling after photorefractive keratectomy. The earliest precursors of myofibroblasts destined to express SMA and desmin are detectible by staining for vimentin at 1 week after surgery. (C) 2009 Elsevier Ltd. All rights reserved.

Quantitative myocardial contrast echocardiography during pharmacological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies

Aims We conducted a meta-analysis to evaluate the accuracy of quantitative stress myocardial contrast echocardiography (MCE) in coronary artery disease (CAD). Methods and results Database search was performed through January 2008. We included studies evaluating accuracy of quantitative stress MCE for detection of CAD compared with coronary angiography or single-photon emission computed tomography (SPECT) and measuring reserve parameters of A, beta, and A beta. Data from studies were verified and supplemented by the authors of each study. Using random effects meta-analysis, we estimated weighted mean difference (WMD), likelihood ratios (LRs), diagnostic odds ratios (DORs), and summary area under curve (AUC), all with 95% confidence interval (0). Of 1443 studies, 13 including 627 patients (age range, 38-75 years) and comparing MCE with angiography (n = 10), SPECT (n = 1), or both (n = 2) were eligible. WMD (95% CI) were significantly less in CAD group than no-CAD group: 0.12 (0.06-0.18) (P < 0.001), 1.38 (1.28-1.52) (P < 0.001), and 1.47 (1.18-1.76) (P < 0.001) for A, beta, and A beta reserves, respectively. Pooled LRs for positive test were 1.33 (1.13-1.57), 3.76 (2.43-5.80), and 3.64 (2.87-4.78) and LRs for negative test were 0.68 (0.55-0.83), 0.30 (0.24-0.38), and 0.27 (0.22-0.34) for A, beta, and A beta reserves, respectively. Pooled DORs were 2.09 (1.42-3.07), 15.11 (7.90-28.91), and 14.73 (9.61-22.57) and AUCs were 0.637 (0.594-0.677), 0.851 (0.828-0.872), and 0.859 (0.842-0.750) for A, beta, and A beta reserves, respectively. Conclusion Evidence supports the use of quantitative MCE as a non-invasive test for detection of CAD. Standardizing MCE quantification analysis and adherence to reporting standards for diagnostic tests could enhance the quality of evidence in this field.

Dynamics of the expression of intermediate filaments vimentin and desmin during myofibroblast differentiation after corneal injury

Previous studies have suggested that abnormal corneal wound healing in patients after photorefractive keratectomy (PRK) is associated with the appearance of myofibroblasts in the stroma between two and four weeks after surgery. The purpose of this study was to examine potential myofibroblast progenitor cells that might express other filament markers prior to completion of the differentiation pathway that yields a-smooth muscle actin (SMA)-expressing myofibroblasts associated with haze localized beneath the epithelial basement membrane after PRK. Twenty-four female rabbits that had -9 diopter PRK were sacrificed at I week, 2 weeks, 3 weeks or 4 weeks after surgery. Corneal rims were collected, frozen at -80 degrees C, and analyzed by immunocytochemistry using anti-vimentin, anti-desmin, and anti-SMA antibodies. Double immunostaining was performed for the co-localization of SMA with vimentin or desmin with SMA. An increase in vimentin expression in stromal cells is noted as early as 1 week after PRK in the rabbit cornea. As the healing response continues at two or three weeks after surgery, many stromal cells expressing vimentin also begin to express desmin and SMA. By 4 weeks after the surgery most, if not all, myofibroblasts express vimentin, desmin and SMA. Generalized least squares regression analysis showed that there was strong evidence that each of the marker groups differed in expression over time compared to the other two (p < 0.01). Intermediate filaments - vimentin and desmin co-exist in myofibroblasts along with SMA and may play an important role in corneal remodeling after photorefractive keratectomy. The earliest precursors of myofibroblasts destined to express SMA and desmin are detectible by staining for vimentin at I week after surgery. (C) 2009 Elsevier Ltd. All rights reserved.

Primary Oral Mucosal Melanoma: A Series of 35 New Cases From South America

Oral mucosal melanoma is rare and reported to be more aggressive than its cutaneous counterpart. Due to the rarity of this entity, data on epidemiology, tumor behavior, treatment, follow-up, and Survival of patients are mainly based oil single case reports. The few existing series of patients show that oral mucosa melanoma has its peak between 4 1 and 60 years of age, and male to female ratio is 2: 1. Preferred oral sites include hard palate and maxillary alveolar crests. Risk factors have not been clearly identified, and surgical treatment is still the treatment of choice for oral mucosal melanomas. The authors retrospectively studied 35 patients with primary melanoma of the oral cavity to report their clinical and pathological features, Such as age, sex, site of the tumor, metastasis, treatment, response to therapy, and Outcome. We found no significant sex predominance, and the mean age of the patients was 60.6 years, with a range From 9 to 91 years. The majority of the patients (71.42%) had palate commitment, and invasive histopathological aspect was observed in 80% of the specimens (grade 3). Long-distance metastasis was found in 60% of the cases. Fourteen patients were submitted to wide Surgical resections, with local relapse being observed in 11 of them (78.5%). The authors Suggest that improved outcome in oral malignant melanoma requires the development of new therapies and the prevention of distant metastasis.

EVALUATION OF ONYX HD-500 EMBOLIC SYSTEM IN THE TREATMENT OF 84 WIDE-NECK INTRACRANIAL ANEURYSMS

OBJECTIVE: We report our results using Onyx HD-500 (Micro Therapeutics, Inc., Irvine, CA) in the endovascular treatment of wide-neck intracranial aneurysms, which have a high rate of incomplete occlusion and recanalization with platinum coils. METHODS: Sixty-nine patients with 84 aneurysms were treated. Most of the aneurysms were located in the anterior circulation (80 of 84 aneurysms), were unruptured (74 of 84 aneurysms), and were incidental. Ten presented with subarachnoid hemorrhage, and 15 were symptomatic. All aneurysms had wide necks (neck >4 mm and/or dome-to-neck ratio <1.5). Fifty aneurysms were small (<12 mm), 30 were large (12 to <25 mm) and 4 were giant. Angiographic follow-up was available for 65 of the 84 aneurysms at 6 months, for 31 of the 84 aneurysms at 18 months, and for 5 of the 84 aneurysms at 36 months. RESULTS: Complete aneurysm occlusion was seen in 65.5% of aneurysms on immediate control, in 84.6% at 6 months, and in 90.3% at 18 months. The rates of complete occlusion were 74%, 95.1%, and 95.2% for small aneurysms and 53.3%, 70%, and 80% for large aneurysms at the same follow-up periods. Progression from incomplete to complete occlusion was seen in 68.2% of all aneurysms, with a higher percentage in small aneurysms (90.9%). Aneurysm recanalization was observed in 3 patients (4.6%), with retreatment in 2 patients (3.3%). Procedural mortality was 2.9%. Overall morbidity was 7.2%. CONCLUSION: Onyx embolization of intracranial wide-neck aneurysms is safe and effective. Morbidity and mortality rates are similar to those of other current endovascular techniques. Larger samples and longer follow-up periods are necessary.

Efficacy and Tolerability of Lodenafil Carbonate for Oral Therapy in Erectile Dysfunction: A Phase II Clinical Trial

Oral treatment with phosphodiesterase type 5 inhibitor (PDE5) is considered the first-line treatment for patients with erectile dysfunction (ED). Lodenafil carbonate (LC) is a novel PDE5. This is a phase II, prospective, randomized, double-blind, and placebo controlled clinical trial of LC. Efficacy end points were International Index of Sexual Function (IIEF) erectile domain, IIEF questions 3 and 4, and Sexual Encounter Profile (SEP) questions 2 and 3, before and after the use of LC or placebo. Seventy-two men older than 18 years, with ED for at least 6 months with stable sexual relationship were enrolled. Patients were randomized to placebo or LC 80 mg, 40 mg, or 20 mg and followed for 4 weeks. IIEF erectile domain scores before and after the use of medications were (mean +/- standard deviation [SD]): placebo: 11.9 +/- 3.4 and 12.6 +/- 5.5; LC 20 mg: 15.8 +/- 4.1 and 18.9 +/- 6.6; LC 40 mg: 11.9 +/- 4.4 and 15.4 +/- 8.1; LC 80 mg: 14.2 +/- 4.7 and 22.8 +/- 6.0 (anova P < 0.01). The SEP-2 scores before and after the use of medications were (Mean +/- SD): placebo: 71.0 +/- 33.1 and 51.2 +/- 43.1; LC 20 mg 70.3 +/- 34.2 and 75.5 +/- 31.5; LC 40 mg: 48.4 +/- 42.1 and 60.8 +/- 42.5; LC 80 mg: 68.6 +/- 33.5 and 89.6 +/- 26.0. The SEP-3 scores were: placebo 23.3 +/- 27.6 and 33.6 +/- 42.3; LC 20 mg: 32.3 +/- 38.9 and 51.2 +/- 41.7; LC 40 mg: 39.7 +/- 44.7 and 46.7 +/- 41.1; LC 80 mg* 17.2 +/- 29.5 and 74.3 +/- 36.4 (*P < 0.05 for difference to placebo). The drug was well tolerated. Adverse reactions were mild and self-limited and included headache, rhinitis, flushing, color visual disorders, and dyspepsia. This study showed that the dosage of 80 mg of LC was significantly more efficacious than placebo and well tolerated. Glina S, Toscano I, Gomatzky C, de Goes PM, Junior AN, de Almeida Claro JF, and Pagani E. Efficacy and tolerability of lodenafil carbonate for oral therapy in erectile dysfunction: A phase II clinical trial. J Sex Med 2009;6:553-557.

Fatigue in amyotrophic lateral sclerosis: Frequency and associated factors

We aimed to quantify fatigue frequency and evolution in amyotrophic lateral sclerosis (ALS), and to correlate fatigue with factors such as age, sex, educational level, disease duration, functionality, quality of life, dyspnoea, depression and sleepiness. Sixty ALS patients (test group: TG) selected by El Escorial criteria and 60 normal individuals (control group: CG) matched according to sex and age, were followed every three months, during 9 months, by means of self-report scales: Fatigue Assessment Instrument (Fatigue Severity Scale plus three qualitative subscales); ALS Functional Rating Scale; McGill Quality of Life Questionnaire; dyspnoea analogical scale; Beck Depression Inventory and Epworth Sleepiness Scale. Fatigue was reported by 83% of TG (median: 3.6, interquartile range 1.5-5.4), compared with 20% of CG (median: 1, 1 - 1), and was significantly greater in the TG (p < 0.001, Mann-Whitney test). Fatigue severity increased by the ninth month of the study (p=0.0008, Friedman, Muller-Dunn post test). There was no correlation between fatigue and other parameters, except for an inverse correlation with age at disease onset (p=0.0395, Spearman rank correlation). In conclusion, fatigue was frequent in ALS, greater in the youngest patients and worsened during follow-up. Possibly, ALS related fatigue is an independent factor, which deserves individualized approach and treatment.