Prenatal express-diagnosis by the method of QF-PCR and automatic microelectroforesis with microarrays

The modern molecular-genetic methods have been implementing actively into the medical practiee.They improve diagnostic accuracy,help to prognosticate the course of oncological diseases,optimize the res...     

Immunological treatment options for locoregionally advanced head and neck squamous cell carcinoma

Patients with squamous cell carcinoma of the head and neck (HNSCC) are usually treated by a multimodal approach with surgery and/or radiochemotherapy as the mainstay of local-regional treatment in cases with advanced disease. Both chemotherapy and radiation therapy have the disadvantage of causing severe side effects, while the clinical outcome of patients diagnosed with HNSCC has remained essentially unchanged over the last decade. The potential of immunotherapy is still largely unexplored. Here the authors review the current status of the art and discuss the future challenges in HNSCC treatment and prevention.     

Anti-inflammatory effects of tobramycin and a copper–tobramycin complex with superoxide dismutase-like activity

Background and Purpose

Airway inflammation in cystic fibrosis (CF) patients is characterized by accumulations of neutrophils in the airway and T cells in bronchial tissue, with activation of platelets in the circulation. CF patients are routinely treated with systemic or inhaled tobramycin for airway infection with Pseudomonas aeruginosa. Clinical trials have indicated an anti-inflammatory effect of tobramycin beyond its bactericidal activity. Here, we investigate the anti-inflammatory properties of tobramycin in vitro and consider if these relate to the ability of tobramycin to bind copper, which is elevated in blood and sputum in CF.

Experimental Approach

A copper–tobramycin complex was synthesized. The effect of tobramycin and copper–tobramycin on neutrophil activation and migration of T cells and neutrophils across human lung microvascular endothelial cells in response to thrombin-activated platelets were investigated in vitro. Tobramycin uptake was detected by immunocytochemistry. Intracellular reactive oxygen species were detected using the fluorescent indicator, 2′,7′-dichlorofluorescein diacetate (DCFDA). Neutrophil superoxide, hydrogen peroxide and neutrophil elastase activity were measured using specific substrates. Copper was measured using atomic absorption spectroscopy.

Key Results

Tobramycin and copper–tobramycin were taken up by endothelial cells via a heparan sulphate-dependent mechanism and significantly inhibited T-cell and neutrophil transendothelial migration respectively. Copper–tobramycin has intracellular and extracellular superoxide dismutase-like activity. Neutrophil elastase inhibition by α1-antitrypsin is enhanced in the presence of copper–tobramycin. Tobramycin and copper–tobramycin are equally effective anti-pseudomonal antibiotics.

Conclusions and Implications

Anti-inflammatory effects of tobramycin in vivo may relate to the spontaneous formation of a copper–tobramycin complex, implying that copper–tobramycin may be more effective therapy.     

Perineurioma of the parotid gland: first case report

SUMMARY: Neurogenic neoplasms account for approximately 1% of salivary gland tumors. A 45-year-old woman presented with a slowly growing unilateral parotid gland mass that was excised completely by lateral parotidectomy. No recurrence was detectable 6 months after surgery. The resection specimen contained a 1.7 × 1.2 × 1-cm whitish nodular lesion that was firm, well circumscribed, and completely surrounded by compressed normal glandular tissue. The tumor was composed of spindle cells with bipolar tapering, wavy nuclei, and palely stained cytoplasm. The tumor cells were arranged in storiform, lamellar, and whorled patterns. Nuclear atypia, necrosis, and significant mitotic activity were absent. Immunohistochemistry showed expression of epithelial membrane antigen, glucose transporter 1, claudin-1, and collagen IV. All other lineage-specific markers including protein S100 were negative in the tumor cells. To our knowledge, this case represents the first report of soft tissue perineurioma in the salivary gland. Lack of previous reports suggests underrecognition of this tumor entity at this unusual anatomical site.     

Combined spontaneous contralateral pneumothorax and post-pneumonectomy mediastinal shift-associated dextrocardia

We report here on an unusual late postoperative presentation of extreme post-pneumonectomy dextrocardia and spontaneous contralateral pneumothorax presenting as late complications occurring approximately 2 years after right-sided pneumonectomy. Computed tomography is the diagnostic modality of choice to obtain information on anatomical changes within the post-pneumonectomy space. Knowledge of the spectrum of cardiopulmonary, pleural, and other complications after lung resection is important to properly manage complications in post-pneumonectomy patients.     

Interaction of gastroesophageal reflux and esophageal motility

The present study addresses the question of whether esophageal motility shortly before, during, and after gastroesophageal reflux (GER) is different in patients with GER disease and healthy controls. Twenty-four-hour continuous recordings of intraesophageal pressures and pH were performed in 12 unselected patients with clinically proven GER disease and in 11 volunteers using a new ambulatory and digital recording device. All GER episodes in each studied subject were classified according to their associated motility pattern shortly before (induction period) and during (response period) GER. More GER episodes were analyzed in patients than in volunteers (median: 41 vs 26, P<0.05), and a total of 917 GER episodes (593 in patients, 324 in volunteers) was recorded. During the induction period patients more often had irregular esophageal contractions (median: 23% vs 13%, P<0.05) and less often had a peristaltic sequence (median: 6% vs 21%) than normals. No difference between patients and controls existed when comparing the frequency of negative pressure peaks or common cavity phenomena shortly before GER. During the response period peristaltic motility in patients was decreased (median: 10% vs 47%, P<0.05). We conclude that: (1) GER events in GER patients are more often associated with irregular esophageal contractions than in healthy controls; (2) GER patients present with a diminished, if any, esophageal peristalsis during GER; and (3) combined ambulatory manometry and pH-metry provides clinically useful information on the individual pathogenesis of GER disease, which is superior to the information retrieved by pH-metry alone.Preliminary results from this study were presented at the Third International Polydisciplinary Congress on Primary Esophageal Motility Disorders in Paris, held from May 19th until 23th 1990.     

An introduction to QT interval prolongation and non-clinical approaches to assessing and reducing risk

Owing to its association with Torsades de Pointes, drug-induced QT interval prolongation has been and remains a significant hurdle to the development of safe, effective medicines. Genetic and pharmacological evidence highlighting the pivotal role the human ether-a-go-go-related gene (hERG) channel was a critical step in understanding how to start addressing this issue. It led to the development of hERG assays with the rapid throughput needed for the short timescales required in early drug discovery. The resulting volume of hERG data has fostered in silico models to help chemists design compounds with reduced hERG potency. In early drug discovery, a pragmatic approach based on exceeding a given potency value has been required to decide when a compound is likely to carry a low QT risk, to support its progression to late-stage discovery. At this point, the in vivo efficacy and metabolism characteristics of the potential drug are generally defined, as well its safety profile, which includes usually a dog study to assess QT interval prolongation risk. The hERG and in vivo QT data, combined with the likely indication and the estimated free drug level for efficacy, are put together to assess the risk that the potential drug will prolong QT in man. Further data may be required to refine the risk assessment before making the major investment decisions for full development. The non-clinical data are essential to inform decisions about compound progression and to optimize the design of clinical QT studies.This article is commented on by Guth and Rast, pp. 22–24 of this issue and is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010