Tumors are heterogeneous masses of cells characterized pathologically by their size and spread. Their chaotic biology makes treatment of malignancies hard to generalize. We present a robust and reproducible glass microfluidic system, for the maintenance and "interrogation" of head and neck squamous cell carcinoma (HNSCC) tumor biopsies, which enables continuous media perfusion and waste removal, recreating in vivo laminar flow and diffusion-driven conditions. Primary HNSCC or metastatic lymph samples were subsequently treated with 5-fluorouracil and cisplatin, alone and in combination, and were monitored for viability and apoptotic biomarker release 'off-chip' over 7 days. The concentration of lactate dehydrogenase was initially high but rapidly dropped to minimally detectable levels in all tumor samples; conversely, effluent concentration of WST-1 (cell proliferation) increased over 7 days: both factors demonstrating cell viability. Addition of cell lysis reagent resulted in increased cell death and reduction in cell proliferation. An apoptotic biomarker, cytochrome c, was analyzed and all the treated samples showed higher levels than the control, with the combination therapy showing the greatest effect. Hematoxylin- and Eosin-stained sections from the biopsy, before and after maintenance, demonstrated the preservation of tissue architecture. This device offers a novel method of studying the tumor environment, and offers a pre-clinical model for creating personalized treatment regimens.
SummaryObjective Optimal thyroxine replacement following total thyroidectomy is critical to avoid symptoms of hypothyroidism. The aim of this study was to determine the best formula to determine the initiated replacement dose of levothyroxine immediately following total thyroidectomy. Design Prospective study. All patients were initiated on 100 lg levothyroxine and titrated to within the reference range for TSH and free T4. Correlations to height, weight, age, lean body mass (LBM), body surface area (BSA) and body mass index (BMI) were calculated. Patients One hundred consecutive adult patients underwent total thyroidectomy for non-malignant disease. Measurements Comparison between three methods of levothyroxine dose prediction, aiming for a levothyroxine dose correct to within 25 lg of actual dose required. Results Correlations were seen between levothyroxine dose and patient age (r = )0AE346, P < 0AE01), bodyweight (r = 0AE296, P < 0AE01), LBM (r = 0AE312, P < 0AE01), BSA (r = 0AE319, P < 0AE01) and BMI (r = 0AE172, P < 0AE05). A regression equation was calculated (predicted levothyroxine dose = [0AE943 · bodyweight] + [)1AE165 · age] + 125AE8), simplified to (levothyroxine dose = bodyweight ) age + 125) pragmatically. Initiating patients empirically on 100 lg post-operatively showed that 40% of patients achieved target within 25 lg of their required dose; this increased to 59% when using a weight-only dose calculation (1AE6 lg/kg) and to 72% using the simplified regression equation. Conclusions A simple calculated regression equation gives a more accurate prediction of initiated levothyroxine dose following total thyroidectomy, reducing the need for outpatient attendance for dose titration.
Our data suggest that ice-lollies are a cheap, effective and safe method of reducing postoperative pain up to one hour following paediatric tonsillectomy.
The surgical procedure requires no specialized equipment and can be performed as a day case. This device complements treatment for patients requiring bone conduction aids and presents as an alternative to conventional percutaneous bone-anchored implants.
Objectives. Chronic cough is a multifactorial symptom that requires multidisciplinary approach. Over the last years, general practitioners refer increasingly more chronic cough patients directly to the otolaryngologist. The aim of this paper is to highlight the issues in diagnosis and management of chronic cough patients from the otolaryngologist perspective. Design. Literature review. Results. Gastroesophageal reflux and postnasal drip syndrome remain one of the most common causes of chronic cough. Better diagnostic modalities, noninvasive tests, and high technology radiological and endoscopic innovations have made diagnosis of these difficult-to-treat patients relatively easier. Multidisciplinary assessment has also meant that at least some of these cases can be dealt with confidently in one stop clinics. Conclusions. As the number of referrals of chronic cough patients to an Ear Nose Throat Clinic increases, the otolaryngologist plays a pivotal role in managing these difficult cases.
Although most respondents use triple therapy of oral antibiotics, steroid nasal spray, and saline douching to some extent, "maximal medical therapy" for chronic rhinosinusitis seems to vary greatly among consultants and frequently does not reflect recent guidelines.
Whilst a multitude of techniques have been employed to study the biology of tumour tissue and its response to chemotherapeutic reagents, most current methodologies do not capture the sophistication of the in vivo environment. Microfluidics however offers the ability to maintain and interrogate primary tissue samples in an environment with biomimetic flow characteristics. In this study head and neck squamous cell carcinoma (HNSCC) tumour biopsies have been used to investigate the performance of a microfluidic device for generating clinically-useful information. The response of fresh and cryogenically-frozen primary HNSCC or metastatic lymph node samples to chemotherapy drugs (cisplatin, 5-flurouracil or docetaxel), alone and in combination, were monitored for both proliferation (water-soluble tetrazolium salt metabolism) and cell death biomarker release (lactate dehydrogenase, LDH) "off-chip". The frozen tissue showed no significant difference in terms of either proliferation or LDH release in comparison with the matched fresh samples. Administration of all drugs caused cell death, in a dose-response manner, with the combination showing the greatest amount of cytotoxicity particularly at days 8 and 9; correlating well with published clinical data. The system described here offers an innovative method for studying the tumour microenvironment in vitro and, through incorporation of relevant analytical modules, provides the basis of a pre-clinical device that can be used to define personalised treatment regimens.
Globus pharyngeus is a common ENT condition. This paper reviews the current evidence on globus and gives a rational guide to the management of patients with globus. The aetiology of globus is still unclear though most ENT surgeons believe that reflux whether acidic or not plays a significant role. Though proton pump inhibitors are used extensively in practice, there is little evidence to support their efficacy. Most patients with globus can be discharged after simple office investigations. The role of pepsin-induced laryngeal injury is an exciting concept that needs further study. Given the benign nature of globus pharyngeus, in most cases, reassurance rather than treatment or extensive investigation with rigid oesophagoscopy or contrast swallows is all that is needed. We need more research into the aetiology of globus.
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