Nasoendoscopy of velopharynx before and during diagnostic therapy

Nasoendoscopy is an important tool for assessing velopharyngeal function. The purpose of this study was to analyze velar and pharyngeal wall movement and velopharyngeal gap during nasoendoscopic evaluation of the velopharynx before and during diagnostic therapy. Nasoendoscopic recordings of 10 children with operated cleft lip and palate were analyzed according to the International Working Group Guidelines. Ratings of movement of velum and pharyngeal walls, and size, location and shape of gaps were analyzed by 3 speech-language pathologists (SLPs). Imaging was obtained during repetitions of the syllable /pa/ during a single nasoendoscopic evaluation: (a) before diagnostic therapy, and (b) after the children were instructed to impound and increase intraoral air pressure (diagnostic therapy). Once the patients impounded and directed air pressure orally, the displacement of the velum, right, left and posterior pharyngeal walls increased 40, 70, 80, and 10%, respectively. Statistical significance for displacement was found only for right and left lateral pharyngeal walls. Reduction in gap size was observed for 30% of the patients and other 40% of the gaps disappeared. Changes in gap size were found to be statistically significant between the two conditions. In nasoendoscopic assessment, the full potential of velopharyngeal displacement may not be completely elicited when the patient is asked only to repeat a speech stimulus. Optimization of information can be done with the use of diagnostic therapy's strategies to manipulate VP function. Assuring the participation of the SLP to conduct diagnostic therapy is essential for management of velopharyngeal dysfunction.

A role for GRK2 in myocardial ischemic injury: indicators of a potential future therapy and diagnostic

Morbidity and mortality of myocardial infarction remains significant with resulting left ventricular function presenting as a major determinant of clinical outcome. Protecting the myocardium against ischemia reperfusion injury has become a major therapeutic goal and the identification of key signaling pathways has paved the way for various interventions, but until now with disappointing results. This article describes the recently discovered new role of G-protein-coupled receptor kinase-2 (GRK2), which is known to critically influence the development and progression of heart failure, in acute myocardial injury. This article focuses on potential applications of the GRK2 peptide inhibitor βARKct in ischemic myocardial injury, the use of GRK2 as a biomarker in acute myocardial infarction and discusses the challenges of translating GRK2 inhibition as a cardioprotective strategy to a possible future clinical application.

Comprehensive evaluation of a somatostatin-based radiolabelled antagonist for diagnostic imaging and radionuclide therapy

Targeting of tumours positive for somatostatin receptors (sst) with radiolabelled peptides is of interest for tumour localization, staging, therapy follow-up and targeted radionuclide therapy. The peptides used clinically are exclusively agonists, but recently we have shown that the radiolabelled somatostatin-based antagonist (111)In-DOTA-sst2-ANT may be preferable to agonists. However, a comprehensive study of this radiolabelled antagonist to determine its significance was lacking. The present report describes the evaluation of this novel antagonist labelled with (111)In and (177)Lu in three different tumour models.

Do we need antiplatelet therapy in thrombocytosis? Pro. Diagnostic and pathophysiologic considerations for a treatment choice.

Thrombocytosis (defined as platelets >450 x 10(9)/l) has several aetiologies. After having excluded spurious thrombocytosis (e. g., due to microspherocytes, schistocytes, cryoglobulins, or bacteria), the differential diagnosis of true thrombocytosis encompasses secondary causes (as diverse as inflammation, infection, malignancy, iron deficiency, or asplenia), primary hereditary (rare forms of familial thrombocytosis) and primary acquired entities (either in the context of a myelodysplastic syndrome or more frequently a myeloproliferative neoplasia). This manuscript addresses the following aspects: 1) diagnostic approach to thrombocytosis; 2) various mechanisms leading to a high platelet count; 3) potential of some of these mechanisms to modulate platelet function, producing hyper-reactive platelets and thus exerting a direct impact on the thrombotic risk; 4) indication of anti-thrombotic treatment in patients with thrombocytosis. There is a single prospective randomized clinical trial showing the benefit of acetyl-salicylic acid in polycythaemia vera. For other types of primary thrombocytosis and for secondary forms, treatment decisions have to be individualized according to the patient thrombotic and bleeding risks, taking into account the mechanism causing thrombocytosis. This manuscript discusses experimental and clinical data suggesting that besides patients with essential thrombocythaemia and other forms of primary thrombocytosis also those with thrombocytosis in the context of chronic inflammation, malignancy, or exposure to high altitude might benefit from anti-platelet treatment.

Clinical and molecular characterization of feline mammary carcinomas overexpressing HER2 proto-oncogene (FMC-HER2+) : new strategies for effective diagnostic and cancer therapy

Tese de Doutoramento em Ciências Veterinárias na Especialidade de Ciências Biológicas e Biomédicas

Gene expression analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of esophageal cancer

OBJECTIVE: This study explored gene expression differences in predicting response to chemoradiotherapy in esophageal cancer. PURPOSE:: A major pathological response to neoadjuvant chemoradiation is observed in about 40% of esophageal cancer patients and is associated with favorable outcomes. However, patients with tumors of similar histology, differentiation, and stage can have vastly different responses to the same neoadjuvant therapy. This dichotomy may be due to differences in the molecular genetic environment of the tumor cells. BACKGROUND DATA: Diagnostic biopsies were obtained from a training cohort of esophageal cancer patients (13), and extracted RNA was hybridized to genome expression microarrays. The resulting gene expression data was verified by qRT-PCR. In a larger, independent validation cohort (27), we examined differential gene expression by qRT-PCR. The ability of differentially-regulated genes to predict response to therapy was assessed in a multivariate leave-one-out cross-validation model. RESULTS: Although 411 genes were differentially expressed between normal and tumor tissue, only 103 genes were altered between responder and non-responder tumor; and 67 genes differentially expressed >2-fold. These included genes previously reported in esophageal cancer and a number of novel genes. In the validation cohort, 8 of 12 selected genes were significantly different between the response groups. In the predictive model, 5 of 8 genes could predict response to therapy with 95% accuracy in a subset (74%) of patients. CONCLUSIONS: This study has identified a gene microarray pattern and a set of genes associated with response to neoadjuvant chemoradiation in esophageal cancer. The potential of these genes as biomarkers of response to treatment warrants further investigation. Copyright © 2009 by Lippincott Williams & Wilkins.

Follicular variant of papillary thyroid carcinoma : a diagnostic challenge for clinicians and pathologists

The follicular variant of papillary thyroid carcinoma (FVPTC) presents a type of papillary thyroid cancer that has created continuous diagnosis and treatment controversies among clinicians and pathologists. In this review, we describe the nomenclature, the clinical features, diagnostic problems and the molecular biology of FVPTC. It is important for clinicians to understand this entity as the diagnosis and management of this group of patient may be different from other patients with conventional PTC. The literature suggests that FVPTC behaves in a way similar, clinically, to conventional papillary thyroid carcinoma. However, there are some genotypic differences which may characterise this neoplasm. These parameters may account for the phenotypic variation described by some scientists in this type of cancer. Further understanding can only be achieved by defining strict pathological criteria, in-depth study of the molecular biology and long term follow-up of the optional patients with FVPTC.

Behçet's syndrome involving the gastrointestinal tract: a diagnostic dilemma in childhood

Behçet's syndrome is very rare in children, especially those under 10 years of age. Clinical and radiological features are described in 4 children, including 2 under the age of 5 years, with the syndrome. As in other pediatric cases reported, the incomplete form of Behçet's syndrome was present in each case. All 4 patients had oral and genital mucosal effects, arthritis and gastrointestinal and dermatological manifestations. Ophthalmological symptoms occurred in only 1 patient. Radiologically, the 4 cases demonstrated the spectrum of gastrointestinal involvement, from minimal irregularity and thickening of the terminal ileum to gross irregularity and deformity of the terminal ileum and cecum. Because of the difficulty in differentiating Behçet's syndrome from other forms of inflammatory bowel disease it is suggested that in children with gastrointestinal involvement, 3 major criteria be present before the diagnosis of Behçet's syndrome is made.

Antibody-targeted nanoparticles for cancer therapy

In recent years, nanoparticulate-mediated drug delivery research has examined a full spectrum of nanoparticles that can be used in diagnostic and therapeutic cancer applications. A key aspect of this technology is in the potential to specifically target the nanoparticles to diseased cells using a range of molecules, in particular antibodies. Antibody-nanoparticle conjugates have the potential to elicit effective targeting and release of therapeutic targets at the disease site, while minimizing off-target side effects caused by dosing of normal tissues. This article provides an overview of various antibody-conjugated nanoparticle strategies, focusing on the rationale of cell-surface receptors targeted and their potential clinical application.

Differences in the diagnostic yield of upper gastrointestinal endoscopy in dyspeptic patients receiving proton-pump inhibitors and H2-receptor antagonists

Patients attending for diagnostic oesophagogastroduodenoscopy (OGD) for dyspeptic symptoms are often receiving acid-suppression therapy that has not been discontinued prior to endoscopy, and this may reduce the diagnostic yield of endoscopy. The aim of this study was to compare the diagnostic yield of OGD in uncomplicated dyspepsia in patients receiving no medication, those receiving acid-suppression therapy, and those receiving nonsteroidal anti-inflammatory drugs (NSAIDs) at the time of endoscopy.

The future of antimicrobial therapy in the era of antibiotic resistance in cystic fibrosis pulmonary infection

Cystic fibrosis (CF) is characterised by chronic polymicrobial airway infection and inflammation, which is the major cause of morbidity and mortality. Aggressive use of antimicrobials has been fundamental in increasing the life expectancy of CF patients in recent years. However, enhanced culture and non-culture based detection methods have identified bacteria in the CF lung not previously isolated from CF patients by routine diagnostic microbiology Coupled with increasing antimicrobial resistance, the future of antimicrobial therapy in CF respiratory infection remains challenging. New strategies are needed to address these problems and ensure improvements in life expectancy are maintained. Potential future strategies include the use of new antimicrobial agents and formulations currently in clinical trials, alternative methods of selecting appropriate therapeutic regimens, determination of the pathogenicity of species newly associated with CF and the development of new antimicrobials and adjuvants for use in clinical practice.

Post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific survival: a nested case-control study in a breast cancer cohort from the UK Clinical Practice Research Datalink

INTRODUCTION: Recent observational studies indicate that post-diagnostic use of aspirin in breast cancer patients may protect against cancer progression perhaps by inhibiting cyclooxygenase-2 dependent mechanisms. Evidence also supports a crucial role for interactions between tumour cells and circulating platelets in cancer growth and dissemination, therefore, use of low-dose aspirin may reduce the risk of death from cancer in breast cancer patients.

METHODS: A cohort of newly diagnosed breast cancer patients (1998 to 2006) were identified in the UK Clinical Practice Research Datalink (and confirmed by cancer registry linkage). Cancer-specific deaths were identified up to 2011 from Office for National Statistics mortality data. A nested case-control analysis was conducted using conditional logistic regression to compare post-diagnostic aspirin exposure using General Practice prescription data in 1,435 cases (breast cancer deaths) with 5,697 controls (matched by age and year of diagnosis).

RESULTS: After breast cancer diagnosis, 18.3% of cancer-specific deaths and 18.5% of matched controls received at least one prescription for low-dose aspirin, corresponding to an odds ratio (OR) of 0.98 (95% CI 0.83, 1.15). Adjustment for potential confounders (including stage and grade) had little impact on this estimate. No dose response relationship was observed when the number of tablets was investigated and no associations were seen when analyses were stratified by receipt of prescriptions for aspirin in the pre-diagnostic period, by stage at diagnosis or by receipt of prescriptions for hormone therapy.

CONCLUSIONS: Overall, in this large population-based cohort of breast cancer patients, there was little evidence of an association between receipt of post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific death. However, information was not available on medication compliance or over-the-counter use of aspirin, which may have contributed to the null findings.