Highlights from the III International Symposium of Thrombosis and Anticoagulation (ISTA), October 14-16, 2010, Sao Paulo, Brazil

To discuss and share knowledge around advances in the care of patients with thrombotic disorders, the Third International Symposium of Thrombosis and Anticoagulation was held in So Paulo, Brazil, from October 14-16, 2010. This scientific program was developed by clinicians for clinicians, and was promoted by four major clinical research institutes: the Brazilian Clinical Research Institute, the Duke Clinical Research Institute of the Duke University School of Medicine, the Canadian VIGOUR Centre, and the Uppsala Clinical Research Center. Comprising 3 days of academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

Combined Laser and Intravitreal Triamcinolone for Proliferative Diabetic Retinopathy and Macular Edema: One-year Results of a Randomized Clinical Trial

PURPOSE: To evaluate laser combined with intravitreal triamcinolone acetonide (IVTA) for the management of patients with proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME). DESIGN: Randomized clinical trial. METHODS: SETTINGS: Single center. STUDY POPULATION: Twenty-two patients with bilateral treatment,naive moderate PDR and CSME. INTERVENTION: Laser (panretinal and macular) photocoagulation was performed in each eye, followed by IVTA in one randomly assigned eye. Best,corrected visual acuity (BCVA), fundus photography, and optical coherence tomography were performed at baseline and at months 1, 3, 6, 9, and 12. MAIN OUTCOME MEASURES:. Changes in BCVA, central macular thickness (CMT), and total macular volume (TMV). RESULTS: The mean logarithm of the minimal angle of resolution (logMAR) BCVA improved significantly, and mean CMT and TMV were significantly reduced in the IVTA group compared with the laser,only group (controls) at all study follow-up visits (P < .001). The mean logMAR BCVA (Snellen equivalent) was 0.44 (20/50(-2)) for the IVTA group and 0.38 (20/50(+1)) for the controls at baseline, and 0.12 (20/25(-1)) for the IVTA group and 0.32 (20/40(-1)) for the controls at 12 months (P < .001.). The mean CMT and TMV were, respectively, 360 mu m and 8.59 mm(3) for the IVTA group and 331 mu m and 8.44 mm(3) for the controls at baseline, and 236 mu m and 7.32 mm(3) for the IVTA group and 266 mu m and 7.78 mm(3) for the controls at 12 months (P < .001). CONCLUSIONS: The combination of laser photocoagulation with IVTA was associated with improved BCVA and decreased CMT and TMV when compared with laser photocoagulation alone for the treatment of moderate PDR with CSME. (Am J Ophthalmol 2009;147:291-297. (C) 2009 by Elsevier Inc. All rights reserved.)

Reciprocal interactions of obstructive sleep apnea and hypertension associated with ACE I/D polymorphism in males

Background: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism gene contributes to the genesis of hypertension (HTN) and may help explain the relationship between obstructive sleep apnea (OSA) and HTN. However, ACE is a pleiotropic gene that has several influences, including skeletal muscle and control of ventilation. We therefore tested the hypothesis that ACE polymorphism influences OSA severity. Methods: Male OSA patients (apnea-hypopnea index [AHI] > 5 events/h) from 2 university sleep centers were evaluated by polysomnography and ACE I/D polymorphism genotyping. Results: We studied 266 males with OSA (age = 48 +/- 13y, body mass index = 29 5kg/m(2), AHI = 34 +/- 25events/h). HTN was present in 114 patients (43%) who were older (p < 0.01), heavier (p < 0.05) and had more severe OSA (p < 0.01). The I allele was associated with HTN in patients with mild to moderate OSA (p < 0.01), but not in those with severe OSA. ACE I/D polymorphism was not associated with apnea severity among normotensive patients. In contrast. the only variables independently associated with OSA severity among patients with hypertension in multivariate analysis were BMI (OR = 1.12) and 11 genotype (OR = 0.27). Conclusions: Our results indicate reciprocal interactions between OSA and HTN with ACE I/D polymorphism, suggesting that among hypertensive OSA males, the homozygous ACE I allele protects from severe OSA. (C) 2009 Elsevier B.V. All rights reserved.

Chloroquine - Induced Hair Depigmentation

A case of hair depigmentation induced by chloroquine diphosphate subacute overdosage in an 11-year-old patient with dermatomyositis is presented. Normal coloured hair growth occurred after normalisation of chloroquine dosage. A discussion on possible pathomechanisms of this phenomenon is made based on experimental data and previously reported patients with the same condition. Lupus (2009) 18, 264-266.

Predictive factors for local recurrence and incomplete resection of early gastric cancer treated by endoscopic resection: A Western experience

BACKGROUND: Early gastric cancer (EGC) is defined as adenocarcinoma limited to the mucosa or submucosa regardless of lymph node involvement. Local EGC recurrence rates have been described ill Lip to 6% of cases. OBJECTIVES: To evaluate predictive factors for incomplete resection and local recurrence of EGC treated by endoscopic mucosal resection (EMR) that was followed up for at least one year. METHODS: From June 1994 to December 2005, 46 patients with EGC underwent EMR. Possible predictive factors for incomplete endoscopic resection and local recurrence were identified by medical chart analysis. Demographic, endoscopic and histopathological data were retrospectively evaluated. EMR was considered complete or incomplete. Patients from the complete resection group were divided into subgroups (with and without local EGC recurrence). RESULTS: Complete resection was possible in 36 cases (76.6%). Predictive factors for incomplete resection were turnout location (P=0.035), histological type (P=0.021), lesion size (P=0.022) and number of resected fragments (P=0.013). On multivariate analysis, undifferentiated histological type (OR 0.8; 95% Cl 0.036 to 0.897) and number of resected fragments (OR 7.34; 95% Cl 1.266 to 42.629) were independent predictive factors for incomplete resection. In the complete resection group, a larger lesion size was associated with a higher the number of resected fragments (P=0.018). Local recurrence occurred in nine cases (25%). Use of the cap technique was the only predictive factor for local recurrence in five of seven cases (71.4%) (P=0.006). CONCLUSIONS: A larger lesion size was associated with a higher number of resected fragments. Undifferentiated adenocarcinoma and piecemeal resection were predictive factors for incomplete resection. Technique type was a predictive factor for local EGC recurrence.

Treadmill running protects spinal cord contusion from secondary degeneration

It is known that physical activity triggers changes in the central nervous system Adult rats, trained on treadmills for 4 weeks, and a group of sedentary rats was submitted to contuse moderate spinal cord injury A group of sedentary rats was submitted to a sham operation The trained group continued running on treadmill after lesion for 4 weeks Motor behavior evaluated by BBB score was smaller in the sedentary group compared to the trained rats by 7 days after lesion Computerized activity monitor showed clear-cut differences in spontaneous motor parameters in trained rats only before lesion After surgery, sedentary rats showed changes in motor parameters but not in later periods of analysis Animals were euthanized by 28 days after surgery, and their spinal cords were processed for Nissl staining and immunohistochemistry The number of the remaining neurons and the lesion areal and lesion volume fractions were obtained by stereological method The number of the remaining neurons did not change after training Lesion volume and lesion areal fraction per section were smaller in the trained group Lesion index was more pronounced in the sedentary group Microdensitometric image analysis demonstrated a microglial reaction, astroglial activation, and glial FGF-2 production more pronounced in the spinal cord of sedentary animals GAP-43 was higher in caudal levels of contusion in the sedentary group In conclusion, treadmill running may favor a better functional recovery in the acute period after spinal cord lesion and wound repair processes leading to neuroprotection (C) 2010 Elsevier B V All rights reserved

Short- and long-term survival of patients with metastatic solid cancer admitted to the intensive care unit: prognostic factors

Decisions for intensive care unit (ICU) admissions in patients with advanced cancer are complex, and the knowledge of survival rates and prognostic factors are essential to these decisions. Ours objectives were to describe the short- and long-term survival of patients with metastatic solid cancer admitted to an ICU due to emergencies and to study the prognostic factors presented at ICU admission that could be associated with hospital mortality. We retrospectively analysed the charts of all patients with metastatic solid cancer admitted over a 1-year period. This gave a study sample of 83 patients. The ICU, hospital, 1-year and 2-year survival rates were 55.4%, 28.9%, 12.0% and 2.4% respectively. Thrombocytopenia (odds ratio 26.2; P = 0.006) and simplified acute physiology score (SAPS II) (odds ratio 1.09; P = 0.026) were independent factors associated with higher hospital mortality. In conclusion, the survival rates of patients with metastatic solid cancer admitted to the ICU due to emergencies were low, but of the same magnitude as other groups of cancer patients admitted to the ICU. The SAPS II score and thrombocytopenia on admission were associated with higher hospital mortality. The characteristics of the metastatic disease, such as number of organs with metastasis and central nervous system metastasis were not associated with the hospital mortality.

Cdx2, cytokeratin 20, thyroid transcription factor 1, and prostate-specific antigen expression in unusual subtypes of prostate cancer

There are some unusual histologic variants of prostate carcinoma, including mucinous, signet-ring cells, and ductal carcinomas that can metastasize in a problematic way and simulate lung, colorectal, or bladder primaries. Currently, antibodies that are organ-specific have been used in the routine surgical pathology practice. Our aim is to study the profile of expression of Cdx2, thyroid transcription factor 1 (TTF1), and cytokeratin 20 (CK20) in prostate cancer with unusual histologic finding. Twenty-nine prostate adenocarcinomas with unusual histologic findings were submitted to immunohistochemistry with prostate-specific antigen (PSA), CK20, Cdx2, and TTF1 antibodies. There were 7 mucinous, 5 ductal, 2 signet-ring cells, and 15 usual acinar adenocarcinomas with focal mucinous differentiation. To compare the results with usual acinar adenocarcinomas, we studied 10 primary and their respective lymph node metastases in a tissue microarray, 2 unusual metastatic adenocarcinomas, and 6 usual acinar high-grade carcinomas. For tumors with special histologic finding, Cdx2 was expressed by 9 (31.0%) mucinous, signet-cell, or with focal mucinous differentiation. Thyroid transcription factor I was moderately positive in mucinous differentiation areas of 2 (6.9%) adenocarcinomas. Cytokeratin 20 was expressed by 9 (31.0%) tumors, among them, 3 ductal adenocarcinomas. Prostate-specific antigen was positive in 28 (96.6%) cases and negative in I ductal adenocarcinoma. There was only I worrisome ductal adenocarcinoma that was strongly CK20 positive and PSA negative. Almost one third of mucinous prostate carcinomas express Cdx2. Cytokeratin 20 can be positive also in one third of prostate carcinomas, especially the ductal type. Pathologist should be alert when evaluating immumohistochemical profiles of unusual histologic findings of prostate cancer, mostly in distant sites. (C) 2008 Elsevier Inc. All rights reserved.

Testosterone represses ubiquitin ligases atrogin-1 and Murf-1 expression in an androgen-sensitive rat skeletal muscle in vivo

Pires-Oliveira M, Maragno AL, Parreiras-E-Silva LT, Chiavegatti T, Gomes MD, Godinho RO. Testosterone represses ubiquitin ligases atrogin-1 and Murf-1 expression in an androgen-sensitive rat skeletal muscle in vivo. J Appl Physiol 108: 266-273, 2010. First published November 19, 2009; doi:10.1152/japplphysiol.00490.2009.-Skeletal muscle atrophy induced by denervation and metabolic diseases has been associated with increased ubiquitin ligase expression. In the present study, we evaluate the influence of androgens on muscle ubiquitin ligases atrogin-1/MAFbx/FBXO32 and Murf-1/Trim63 expression and its correlation with maintenance of muscle mass by using the testosterone-dependent fast-twitch levator ani muscle (LA) from normal or castrated adult male Wistar rats. Gene expression was determined by qRT-PCR and/or immunoblotting. Castration induced progressive loss of LA mass (30% of control, 90 days) and an exponential decrease of LA cytoplasm-to-nucleus ratio (nuclear domain; 22% of control after 60 days). Testosterone deprivation induced a 31-fold increase in LA atrogin-1 mRNA and an 18-fold increase in Murf-1 mRNA detected after 2 and 7 days of castration, respectively. Acute (24 h) testosterone administration fully repressed atrogin-1 and Murf-1 mRNA expression to control levels. Atrogin-1 protein was also increased by castration up to 170% after 30 days. Testosterone administration for 7 days restored atrogin-1 protein to control levels. In addition to the well known stimulus of protein synthesis, our results show that testosterone maintains muscle mass by repressing ubiquitin ligases, indicating that inhibition of ubiquitin-proteasome catabolic system is critical for trophic action of androgens in skeletal muscle. Besides, since neither castration nor androgen treatment had any effect on weight or ubiquitin ligases mRNA levels of extensor digitorum longus muscle, a fast-twitch muscle with low androgen sensitivity, our study shows that perineal muscle LA is a suitable in vivo model to evaluate regulation of muscle proteolysis, closely resembling human muscle responsiveness to androgens.

Study of spontaneous recurrent seizures and morphological alterations after status epilepticus induced by intrahippocampal injection of pilocarpine

Epileptic seizures are clinical manifestations of neuronal discharges characterized by hyperexcitability and/or hypersynchrony in the cortex and other subcortical regions. The pilocarpine (PILO) model of epilepsy mimics temporal lobe epilepsy (TLE) in humans. In the present study, we used a more selective approach: microinjection of PILO into the hilus of the dentate gyrus (H-PILO). Our main goal was to evaluate the behavioral and morphological alterations present in this model of TLE. Seventy-six percent of all animals receiving H-PILO injections had continuous seizures called status epilepticus (SE). A typical pattern of evolution of limbic seizures during the SE with a latency of 29.3 +/- 16.3 minutes was observed using an analysis of behavioral sequences. During the subsequent 30 days, 71% of all animals exhibited spontaneous recurrent seizures (SRSs) during a daily 8-hour videotaping session. These SRSs had a very conspicuous and characteristic pattern detected by behavioral sequences or neuroethological analysis. Only the animals that had SE showed positive Neo-Timm staining in the inner molecular layer of the dentate gyrus (sprouting) and reduced cell density in Ammon`s horn pyramidal cell subfield CA1. However, no correlation between the intensity of sprouting and the mean number and total number of SRSs was found. Additionally, using Fluoro-Jade staining, we observed neurodegeration in the hilus and pyramidal cell subfields CA3 and CM 24 hours after SE. These data indicate that H-PILO is a reliable, selective, efficient, low-mortality model that mimics the acute and chronic behavioral and morphological aspects of TLE. (C) 2010 Elsevier Inc. All rights reserved.

Further Study of the Psychometric Qualities of a Brief Screening Tool for Social Phobia (MINI-SPIN) Applied to Clinical and Nonclinical Samples

PURPOSE. The purpose of this study was to further assess the psychometric qualities of the Mini-Social Phobia Inventory (MS) to screen for social anxiety disorder (SAD). DESIGN AND METHODS. The MS and other self- and clinician-rated scales for anxiety and social anxiety were applied in 2,314 university students and in samples of SAD patients (n = 88) and nonpatients (n = 90). FINDINGS. The MS revealed adequate discriminative validity, internal consistency (alpha = 0.49-0.73), convergent validity with the Social Phobia Inventory, Brief Social Phobia Scale, and Self-Statements During Public Speaking Scale and convergent and divergent validity with the Beck Anxiety Inventory. PRACTICE IMPLICATIONS. The MS has shown to be a fast and efficient screening instrument for SAD in different cultures and contexts.

Dorsal root ganglionectomy for the diagnosis of sensory neuropathies. Surgical technique and results

Background: Inflammatory diseases stand out among sensory neuronopathies because, in their active phase, they can be treated with immunosuppressive agents. Immunosuppressive therapy may present severe adverse effects and requires previous inflammatory activity confirmation. Sensory neuronopathies are diagnosed based on clinical and EMG findings. Diagnostic confirmation and identification of inflammatory activity are based on sensory ganglion histopathological examination. We describe the surgical technique used for dorsal root ganglionectomy in patients with clinical/EMG diagnosis of sensory neuronopathies. Methods: The sensory ganglion was obtained from 15 patients through a small T7-T8 hemilaminectomy and foraminotomy to expose the C7 root from its origin to the spinal nerve bifurcation. In 6 patients, the dural cuff supposed to contain the ganglion was resected en bloc; and in 9 patients, the ganglion was obtained through a longitudinal incision of the dural cuff and microsurgical dissection from the ventral and dorsal roots and radicular arteries. All ganglia were histopathologically examined. Results: No ganglion was found in the dural cuff in 2 patients submitted to en bloc removal, and the ganglion was removed in all patients who underwent microsurgical dissection. All but 2 patients that had ganglion examination presented a neuronopathy of nerve cell loss, 3 with mononuclear inflammatory infiltrate. These patients underwent immunosuppressive therapy, and 2 of them presented clinical improvement. No surgical complications were observed. Conclusions: Microsurgical dorsal root ganglionectomy for diagnosing inflammatory sensory ganglionopathies was effective and safe. Although safe, en bloc resection of the proximal dural cuff was not effective for this purpose. (c) 2008 Published by Elsevier Inc.

Prevalence of Rickettsia species antibodies and Rickettsia species DNA in the blood of cats with and without fever

Rickettsia species antibodies have been detected in some cats but it is unknown whether infected cats develop clinical signs. The prevalence of Rickettsia species deoxyribonucleic acid (DNA) in blood from clinically ill cats has not been determined. The objective of this study was to determine if cats with fever (body temperature >= 102.5 degrees F [39.2 degrees C]) were more likely to have evidence of rickettsial infection than healthy, age-matched, control cats with a body temperature < 102.5 degrees F. Rickettsia species polymerase chain reaction (PCR) assays were performed to detect rickettsial DNA extracted from blood (71 paired samples), indirect immunofluorescence assays (IFA) were performed to detect serum antibodies against Rickettsia felis (90 paired samples) and Rickettsia rickettsii (91 paired samples), and the results between pairs were compared. All samples were negative for Rickettsia species DNA. More cats with fever were seropositive for R felis or R rickettsii than control cats, but results were not statistically significant. Results of this pilot study failed to show an association between Rickettsia species DNA or Rickettsia species antibodies and fever. (c) 2008 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Immediate Effect of the Resilient Splint Evaluated Using Surface Electromyography in Patients with TMD

The aim of this study was to analyze the immediate effect of resilient splints through surface electromyography testing and to compare the findings with the electromyographic profiles of asymptomatic subjects. The participants were 30 subjects, 15 patients with TMD (TMD Group) and 15 healthy subjects (Control Group), classified according to Research Diagnostic Criteria (RDC/TMD) Axis I. A resilient occlusal splint was made for each patient in the TMD Group from two mm thick silicon to cover all teeth. The EMG examination was performed before and immediately after installing the splint. Three tests were performed as follows: 1. Maximum Voluntary Contraction (MVC) using cotton rolls (standards test); 2. MVC in maximal intercuspation position; and 3. MVC with the splint in position. The EMG signal was recorded for five seconds. EMG indices were calculated to assess muscle symmetry, jaw torque, and impact. There was a statistically significant difference when comparing the results among the study groups. The symmetry index values in the Control Group were higher than the TMD Initial Group and similar to the TMD Group after the installation of the splint. The index values of torque were higher in TMD Initial Group when compared with the Controls. Impact values were lower than normal values in the TMD Initial Group and restored upon installation of the splint. The resilient occlusal splints may be used as complementary or adjunctive treatment of temporomandibular disorders.