Update to the College of American Pathologists Reporting on Thyroid Carcinomas

Background The reporting of thyroid carcinomas follows the recommendations of the College of American Pathologists (CAP) protocols and includes papillary carcinoma, follicular carcinoma, anaplastic carcinoma and medullary carcinoma. Despite past and recent efforts, there are a number of controversial issues in the classification and diagnosis of thyroid carcinomas (TC) that, potentially impact on therapy and prognosis of patients with TC. Discussion The most updated version of the CAP thyroid cancer protocol incorporates recent changes in histologic classification as well as changes in the staging of thyroid cancers as per the updated American Joint Commission on Cancer staging manual. Among the more contentious issues in the pathology of thyroid carcinoma include the defining criteria for tumor invasiveness. While there are defined criteria for invasion, there is not universal agreement in what constitutes capsular invasion, angioinvasion and extrathyroidal invasion. Irrespective of the discrepant views on invasion, pathologists should report on the presence and extent (focal, widely) of capsular invasion, angioinvasion and extrathyroidal extension. These findings assist clinicians in their assessment of the recurrence risk and potential for metastatic disease. It is beyond the scope of this paper to detail the entire CAP protocol for thyroid carcinomas; rather, this paper addresses some of the more problematic issues confronting pathologists in their assessment and reporting of thyroid carcinomas. Conclusion The new CAP protocol for reporting of thyroid carcinomas is a step toward improving the clinical value of the histopathologic reporting of TC. Large meticulous clinico-pathologic and molecular studies with long term follow up are still needed in order to increase the impact of microscopic examination on the prognosis and management of TC

Glandular Odontogenic Cyst: Report of Two Cases and Review of Literature

Glandular odontogenic cyst (GOC) is an uncommon jaw bone cyst of odontogenic origin described in 1987 by Gardner et al. It is a cyst having an unpredictable and potentially aggressive behaviour. It also has the propensity to grow to a large size and tendency to recur with only 111 cases having been reported thus far. The first case occurred in a 42-year-old female and presented as a localized swelling extending from 19 to 29 regions. There was a history of traumatic injury at the site. There was evidence of bicortical expansion and radiographs revealed a multilocular radiolucency. The second case occurred in a 21-year-old male, as a large swelling in the mandible and radiograph revealed radiolucency in the region. On histopathological examination, these lesions were diagnosed as GOC. It was concluded that, two cases submitted by us correlate with the existing literature that GOC’s affect more commonly in the middle age group, having predilection for mandible and that trauma could be a precipitating factor for its occurrence. The increased recurrence rates can be due to its intrinsic biological behavior, multilocularity of the cyst, and incomplete removal of the lining following conservative treatment

In vivo Hypoxia and a Fungal Alcohol Dehydrogenase Influence the Pathogenesis of Invasive Pulmonary Aspergillosis

Currently, our knowledge of how pathogenic fungi grow in mammalian host environments is limited. Using a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA) and 1H-NMR metabolomics, we detected ethanol in the lungs of mice infected with Aspergillus fumigatus. This result suggests that A. fumigatus is exposed to oxygen depleted microenvironments during infection. To test this hypothesis, we utilized a chemical hypoxia detection agent, pimonidazole hydrochloride, in three immunologically distinct murine models of IPA (chemotherapeutic, X-CGD, and corticosteroid). In all three IPA murine models, hypoxia was observed during the course of infection. We next tested the hypothesis that production of ethanol in vivo by the fungus is involved in hypoxia adaptation and fungal pathogenesis. Ethanol deficient A. fumigatus strains showed no growth defects in hypoxia and were able to cause wild type levels of mortality in all 3 murine models. However, lung immunohistopathology and flow cytometry analyses revealed an increase in the inflammatory response in mice infected with an alcohol dehydrogenase null mutant strain that corresponded with a reduction in fungal burden. Consequently, in this study we present the first in vivo observations that hypoxic microenvironments occur during a pulmonary invasive fungal infection and observe that a fungal alcohol dehydrogenase influences fungal pathogenesis in the lung. Thus, environmental conditions encountered by invading pathogenic fungi may result in substantial fungal metabolism changes that influence subsequent host immune responses

Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study

<p>Background: High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT[1]study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study.</p> <p>The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting.</p> <p>Methods/design: The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios.</p> <p>Primary Objective – To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios.</p> <p>Secondary Objectives – To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendrofluazide.</p> <p>Discussion: The numerous deleterious effects of hypertension dictate the need for a systematic approach for its treatment. In spite of various therapies, resistant hypertension is widely prevalent. Among various factors, primary aldosteronism is an important cause of resistant hypertension and is now more commonly recognised. More significantly, hypertensives with primary aldosteronism are also exposed to various other deleterious effects of excess aldosterone. Hence treating hypertension with specific aldosterone antagonists may be a better approach in this group of patients. It may lead on to better blood pressures with fewer medications.</p&gt

Population Genetic Analysis Infers Migration Pathways of Phytophthora ramorum in US Nurseries

Recently introduced, exotic plant pathogens may exhibit low genetic diversity and be limited to clonal reproduction. However, rapidly mutating molecular markers such as microsatellites can reveal genetic variation within these populations and be used to model putative migration patterns. Phytophthora ramorum is the exotic pathogen, discovered in the late 1990s, that is responsible for sudden oak death in California forests and ramorum blight of common ornamentals. The nursery trade has moved this pathogen from source populations on the West Coast to locations across the United States, thus risking introduction to other native forests. We examined the genetic diversity of P. ramorum in United States nurseries by microsatellite genotyping 279 isolates collected from 19 states between 2004 and 2007. Of the three known P. ramorum clonal lineages, the most common and genetically diverse lineage in the sample was NA1. Two eastward migration pathways were revealed in the clustering of NA1 isolates into two groups, one containing isolates from Connecticut, Oregon, and Washington and the other isolates from California and the remaining states. This finding is consistent with trace forward analyses conducted by the US Department of Agriculture's Animal and Plant Health Inspection Service. At the same time, genetic diversities in several states equaled those observed in California, Oregon, and Washington and two-thirds of multilocus genotypes exhibited limited geographic distributions, indicating that mutation was common during or subsequent to migration. Together, these data suggest that migration, rapid mutation, and genetic drift all play a role in structuring the genetic diversity of P. ramorum in US nurseries. This work demonstrates that fast-evolving genetic markers can be used to examine the evolutionary processes acting on recently introduced pathogens and to infer their putative migration patterns, thus showing promise for the application of forensics to plant pathogens

Project Masihambisane: a cluster randomised controlled trial with peer mentors to improve outcomes for pregnant mothers living with HIV

Abstract Background Pregnant women living with HIV (WLH) face daily challenges maintaining their own and their babies' health and mental health. Standard Prevention of Maternal to Child Transmission (PMTCT) programs are not designed to address these challenges. Methods/Design As part of a cluster randomized controlled trial, WLH are invited to attend four antenatal and four postnatal small group sessions led by a peer WLH (a Peer Mentor). The WLH and their babies are assessed during pregnancy and at one week, six months, and twelve months post-birth. Mobile phones are used to collect routine information, complete questionnaires and remain in contact with participants over time. Pregnant WLH (N = 1200) are randomly assigned by clinic (N = 8 clinics) to an intervention program, called Masihambisane (n = 4 clinics, n = 600 WLH) or a standard care PMTCT control condition (n = 4 clinics; n = 600 WLH). Discussion Data collection with cellular phones are innovative and effective in low-resource settings. Standard PMTCT programs are not designed to address the daily challenges faced by WLH; Peer Mentors may be useful in supporting WLH to cope with these challenges. Trial registration ClinicalTrials.gov registration # NCT0097269