Treatment of mechanically-induced vasospasm of the carotid artery in a primate using intra-arterial verapamil: a technical case report

BACKGROUND: Despite improvements in the safety and efficacy of endovascular procedures, considerable morbidity may still be attributed to vasospasm. Vasospasm has proven amenable to pharmacological intervention such as nitrates, intravenous calcium channel blockers (CCBs), and intra-arterial papaverine, particularly in small vessels. However, few studies have focused on medium to large vessel spasm. Here we report the use of an intra-arterial CCB, verapamil, to treat flow-limiting mechanically-induced spasm of the common carotid artery (CCA) in a primate. We believe this to be the first such report of its kind. CASE PRESENTATION: As part of a study assessing the placement feasibility and safety of a catheter capable of delivering intra-arterial cerebroprotective therapy, a female 16 kg baboon prophylaxed with intravenous nitroglycerin underwent transfemoral CCA catheterization with a metallic 6-Fr catheter without signs of acute spasm. The protocol dictated that the catheter remain in the CCA for 12 hours. Upon completion of the protocol, arteriography revealed a marked decrease in CCA size (mean cross-sectional area reduction = 31.6 ± 1.9%) localized along the catheter length. Intra-arterial verapamil (2 mg/2cc) was injected and arteriography was performed 10 minutes later. Image analysis at 6 points along the CCA revealed a 21.0 ± 1.7% mean increase in vessel diameter along the length of the catheter corresponding to a 46.7 ± 4.0% mean increase in cross-sectional area. Mean systemic blood pressure did not deviate more than 10 mm Hg during the procedure. CONCLUSIONS: Intraluminal CCBs like verapamil may constitute an effective endovascular treatment for mechanically-induced vasospasm in medium to large-sized vessels such as the CCA

The self-reported Montgomery-Åsberg depression rating scale is a useful evaluative tool in major depressive disorder

Abstract Background The use of Patient-reported Outcomes (PROs) as secondary endpoints in the development of new antidepressants has grown in recent years. The objective of this study was to assess the psychometric properties of the 9-item, patient-administered version of the Montgomery-Åsberg Depression Rating Scale (MADRS-S). Methods Data from a multicentre, double-blind, 8-week, randomised controlled trial of 278 outpatients diagnosed with Major Depressive Disorder were used to evaluate the validity, reliability and sensitivity to change of the MADRS-S using psychometric methods. A Receiver Operating Characteristic (ROC) curve was plotted to identify the most appropriate threshold to define perceived remission. Results No missing values were found at the item level, indicating good acceptability of the scale. The construct validity was satisfactory: all items contributed to a common underlying concept, as expected. The correlation between MADRS-S and physicians' MADRS was moderate (r = 0.54, p Conclusion Taking account of patient's perceptions of the severity of their own symptoms along with the psychometric properties of the MADRS-S enable its use for evaluative purposes in the development of new antidepressant drugs.</p

Ethanol Oxidation and Toxicity: Role of Alcohol P-450 Oxygenase

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66172/1/j.1530-0277.1986.tb05179.x.pd

Topoisomerase II alpha gene copy loss has adverse prognostic significance in ERBB2-amplified breast cancer: a retrospective study of paraffin-embedded tumor specimens and medical charts

<p>Abstract</p> <p>Background</p> <p>Amplification of the <it>ERBB2 </it>(<it>Her-2/neu</it>) oncogene, which occurs in approximately 25% of breast carcinomas, is a known negative prognostic factor. Available data indicate that a variable number of nearby genes on chromosome 17q may be co-amplified or deleted, forming a continuous amplicon of variable size. In approximately 25% of these patients, the amplicon extends to the gene for <it>topoisomerase II alpha </it>(<it>TOP2A</it>), a target for anthracyclines. We sought to understand the significance of these associated genomic changes for breast cancer prognosis and predicting response to therapy.</p> <p>Methods and patients</p> <p>Archival tissue samples from 63 breast cancer patients with <it>ERBB2 </it>amplification, stages 0–IV, were previously analyzed with FISH probes for genes located near <it>ERBB2</it>. In the present study, the clinical outcome data were determined for all patients presenting at stages I–III for whom adequate clinical follow up was available.</p> <p>Results</p> <p>Four amplicon patterns (Classes) were identified. These were significantly associated with the clinical outcome, specifically, recurrence of breast cancer. The Amplicon class IV with deleted <it>TOP2A </it>had 67% (6/9) cases with recurrence, whereas the other three classes combined had only 12% (3/25) cases (p-value = 0.004) at the time of last follow-up. <it>TOP2A </it>deletion was also significantly associated with time to recurrence (p-value = 0.0002). After adjusting for age in Cox regression analysis, the association between <it>TOP2A </it>deletion and time to recurrence remains strongly significant (p-value = 0.002) whereas the association with survival is marginally significant (p-value = 0.06).</p> <p>Conclusion</p> <p><it>TOP2A </it>deletion is associated with poor prognosis in <it>ERBB2</it>-amplified breast carcinomas. Clarification of the mechanism of this association will require additional study.</p

NEFL mRNA Expression Level Is a Prognostic Factor for Early-Stage Breast Cancer Patients

Neurofilament, light polypeptide (NEFL) was demonstrated to be ectopically expressed in breast cancer tissues and decreased in lymph node metastases compared to the paired primary breast cancers in our previous study. Moreover, in several studies, NEFL was regarded as a tumor suppressor gene, and its loss of heterozygosity (LOH) was related to carcinogenesis and metastasis in several types of cancer. To explore the role of NEFL in the progression of breast cancer and to evaluate its clinical significance, we detected the NEFL mRNA level in normal breast tissues, primary breast cancer samples and lymph node metastases, and then analyzed the association between the NEFL expression level and several clinicopathological parameters and disease-free survival (DFS). NEFL mRNA was found to be expressed in 92.3% of breast malignancies and down-regulated in lymph node metastases compared to the paired primary tumors. NEFL mRNA level was lower in primary breast cancers with positive lymph nodes than in cancers with negative lymph nodes. Moreover, a low expression level of NEFL mRNA indicated a poor five-year DFS for early-stage breast cancer patients. Thus, NEFL mRNA is ectopically expressed in breast malignancies and could be a potential prognostic factor for early-stage breast cancer patients

The Role of Neighborhood Environment in Promoting Risk Factors of Cardiovascular Disease among Young Adults: Data from Middle to High Income Population in an Asian Megacity

Background: Modifiable risk factors of cardiovascular diseases (CVD) have their triggers in the neighborhood environments of communities. Studying the environmental triggers for CVD risk factors is important to understand the situation in a broader perspective. Young adults are influenced the most by the environment profile around them hence it is important to study this subset of the population.Methods: This was a descriptive study conducted using the EPOCH research tool designed by the authors of the PURE study. The study population consisted of young adults aged 18-25 in two areas of Karachi. The study setting was busy shopping malls frequented by young adults in the particular community being studied.Results: Our total sample size was 120 individuals, who consented to be interviewed by our interviewers. Less than 50% of the population recognized some form of restriction regarding smoking in their communities. The largest contributor to tobacco advertising was actors smoking in movies and TV shows with 89% responses from both communities. Only 11.9% of the individuals disapproved of smoking cigarettes among men with wide acceptance of \u27sheesha\u27 across all age groups. Advertising for smoking and junk food was more frequent as compared to smoking cessation, healthy diet and exercise in both the areas. Unhealthy food items were more easily available in contrast to healthier options. The cost of healthy snack food options including vegetables and fruits was higher than sugary drinks and foods.CONCLUSION: This assessment showed that both communities were exposed to environments that promote risk factors for cardiovascular diseases

Molecular subtypes of breast cancer and amplification of topoisomerase IIα: predictive role in dose intensive adjuvant chemotherapy

Benefit from chemotherapy treatment in breast cancer patients is determined by the molecular make-up of the tumour. In a retrospective analysis, we determined the molecular subtypes of breast cancer originally defined by expression microarrays by immunohistochemistry in tumours of patients who took part in a randomised study of adjuvant high-dose chemotherapy in breast cancer. In addition, the topoisomerase IIα (TOP2A) amplification status was determined by fluorescence in situ hybridisation and chromogenic in situ hybridisation. 411 of the 753 tumours (55%) were classified as luminal-like, 137 (18%) as basal-like and 205 (27%) as human epithelial receptor type 2 (HER2) amplified. The basal-like tumours were defined as having no expression of ER and HER2; 98 of them did express epidermal growth factor receptor and/or cytokeratin 5/6. The luminal-like tumours had a significantly better recurrence free and overall survival than the other two groups. From the 194 HER2-positive tumours, 47 (24%) were shown to harbour an amplification of TOP2A. Patients with an HER2-amplified tumour randomised to the high-dose therapy arm did worse than those in the conventional treatment arm, possibly caused by the lower cumulative anthracycline dose in the high-dose arm. The tumours with a TOP2A amplification contributed hardly to this difference, suggesting that TOP2A amplification is not the cause of the steep dose–response curve for anthracyclines in breast cancer. Possibly, the difference of the cumulative dose of only 25% between the treatment arms was insufficient to yield a survival difference

The Relationship Between Homework Compliance and Therapy Outcomes: An Updated Meta-Analysis

The current study was an updated meta-analysis of manuscripts since the year 2000 examining the effects of homework compliance on treatment outcome. A total of 23 studies encompassing 2,183 subjects were included. Results indicated a significant relationship between homework compliance and treatment outcome suggesting a small to medium effect (r = .26; 95% CI = .19–.33). Moderator analyses were conducted to determine the differential effect size of homework on treatment outcome by target symptoms (e.g., depression; anxiety), source of homework rating (e.g., client; therapist), timing of homework rating (e.g., retroactive vs. contemporaneous), and type of homework rating (e.g., Likert; total homeworks completed). Results indicated that effect sizes were robust across target symptoms, but differed by source of homework rating, timing of homework rating, and type of homework rating. Specifically, studies utilizing combined client and therapist ratings of compliance had significantly higher mean effect size relative to those using therapist only assessments and those using objective assessments. Further, studies that rated the percentage of homeworks completed had a significantly lower mean effect size compared to studies using Likert ratings, and retroactive assessments had higher effect size than contemporaneous assessments

Structural motifs recurring in different folds recognize the same ligand fragments

<p>Abstract</p> <p>Background</p> <p>The structural analysis of protein ligand binding sites can provide information relevant for assigning functions to unknown proteins, to guide the drug discovery process and to infer relations among distant protein folds. Previous approaches to the comparative analysis of binding pockets have usually been focused either on the ligand or the protein component. Even though several useful observations have been made with these approaches they both have limitations. In the former case the analysis is restricted to binding pockets interacting with similar ligands, while in the latter it is difficult to systematically check whether the observed structural similarities have a functional significance.</p> <p>Results</p> <p>Here we propose a novel methodology that takes into account the structure of both the binding pocket and the ligand. We first look for local similarities in a set of binding pockets and then check whether the bound ligands, even if completely different, share a common fragment that can account for the presence of the structural motif. Thanks to this method we can identify structural motifs whose functional significance is explained by the presence of shared features in the interacting ligands.</p> <p>Conclusion</p> <p>The application of this method to a large dataset of binding pockets allows the identification of recurring protein motifs that bind specific ligand fragments, even in the context of molecules with a different overall structure. In addition some of these motifs are present in a high number of evolutionarily unrelated proteins.</p

The Heritability of Aptitude and Exceptional Talent Across Different Domains in Adolescents and Young Adults

The origin of individual differences in aptitude, defined as a domain-specific skill within the normal ability range, and talent, defined as a domain specific skill of exceptional quality, is under debate. The nature of the variation in aptitudes and exceptional talents across different domains was investigated in a population based twin sample. Self-report data from 1,685 twin pairs (12–24 years) were analyzed for Music, Arts, Writing, Language, Chess, Mathematics, Sports, Memory, and Knowledge. The influence of shared environment was small for both aptitude and talent. Additive and non-additive genetic effects explained the major part of the substantial familial clustering in the aptitude measures with heritability estimates ranging between .32 and .71. Heritability estimates for talents were higher and ranged between .50 and .92. In general, the genetic architecture for aptitude and talent was similar in men and women. Genetic factors contribute to a large extent to variation in aptitude and talent across different domains of intellectual, creative, and sports abilities