Mucociliary function of the eustachian tube in the eustachian tube dysfunction

Background: Most of the tests to evaluate the eustachian tube (ET) function are focused on the ventilation function of the ET.

Aim: Here we evaluate mucociliary function of the ET in patients with ET dysfunction.

Materials and methods: Ten patients with ET dysfunction were enrolled into the study. Six patients had chronic tympanic membrane retraction and four patients had chronic middle ear effusion (MEE). All patients had intact tympanic membranes. Tympanometry and clinical examinations were done to all patients. Mucociliary function was evaluated with technetium labeled albumin and blue dye. Tympanometry and clinical examinations were done to six patients with chronic tympanic membrane retraction and four patients with chronic middle ear effusion (MEE). Mucociliary function of the ET was evaluated with technetium labeled albumin and blue dye placed into middle ear through an intact tympanic membrane and followed from nasopharynx ET orifice (blue dye) and with gamma camera (technetium).

Results: Blue dye was observed in tubal orifice in six (6 of 10) patients during 30?min observation. Five of those patients (5 of 6) had tympanic membrane retraction and one patient (1 of 6) had MEE. Tracer activity decreased from middle ear in six (6 of 10) patients. Four of those patients had tympanic membrane retraction and two had MEE.

Conclusion: Mucociliary function of the ET seems to be better in patients with tympanic membrane retraction than patients with middle ear effusion.

Significance: Mucociliary function of the ET is an important function for middle ear aeration, blue dye test is easily available to be used also in clinical practice.     

Osteoclasts in neurofibromatosis type 1 display enhanced resorption capacity,aberrant morphology,and resistance to serum deprivation

Neurofibromatosis 1 syndrome (NF1) presents with skeletal involvement suggesting that altered bone dynamics is associated with NF1. Histological analysis of three cases of NF1-related pseudarthrosis revealed numerous osteoclasts in contact with adjacent bone, and within the pseudarthrosis tissue itself. These findings prompted us to evaluate the differentiation and resorption capacity of NF1-osteoclast like cells (OLCs) in vitro. Osteoclast progenitors were isolated from peripheral blood of 17 patients with NF1 and allowed to differentiate into OLCs on bone slices. The following differences were found between NF1 and control samples: samples from NF1 patients resulted in a higher number of resorbing OLCs; NF1 OLCs were larger in size; their nuclei were more numerous; actin rings were more frequent; and the resorption pits in NF1 samples were more numerous and larger. Bone resorption markers revealed that the resorption activity in NF1 OLC cultures was approximately two times higher than in controls. Following deprivation from serum, the number of NF1 OLCs remained essentially the same during 24 h, whereas the number of control OLCs was dramatically reduced during the same time. Three patients had NF1-related lytic bone lesions, and their in vitro results differed from those of other patients. Our results demonstrate that OLCs derived from blood of patients with NF1 display elevated resorption activity under conditions isolated from microenvironment operative in vivo. Thus, increased osteoclast activity may be a phenotypic property of the NF1 syndrome, and at least in part explain selected skeletal findings in NF1, such as osteoporosis/osteopenia.     

Double-guidewire-assisted cannulation in ERCP: novel applications

Even in experienced hands, a common problem at endoscopic retrograde cholangiopancreatography (ERCP) is difficulty in reaching a selective cannulation of the common bile duct or pancreatic duct. The success rate of biliary cannulation has improved markedly in many centers after the adoption of double-guidewire-assisted cannulation technique in cases in which the guidewire repeatedly passes into the pancreatic duct although the common bile duct is intended. Here, we describe 2 novel applications of the double-guidewire technique for difficult cannulation in ERCP. In particular, we emphasize that in addition to difficult biliary cannulation, double-guidewire technique may prove useful in difficult pancreatic cannulation. The double-guidewire technique is feasible also in cases in which the guidewire repeatedly passes into the cystic duct instead of the intended common hepatic duct and intrahepatic radicals. ERCP endoscopists should be aware of all modifications of double-guidewire technique to further increase the success rates of selective cannulations in ERCP.     

Selection of criteria for assessment of occlusal acceptability

There is no general agreement on criteria that could be applied to distinguish between orthodontically acceptable and non-acceptable occlusions after the completion of dental development. The aim of the present study was to analyse morphological and functional features that could be used as an index to define an acceptable occlusion in young adults. Three expert panels representing specialists in orthodontics and stomatognathic physiology participated in a modified Delphi method. Each panel responded to a questionnaire concerning the usefulness of various occlusal features, and a set of characteristics was selected on the basis of the responses; thereafter, applicability of the chosen characteristics and their cut-offs for an acceptable non-acceptable dichotomy was tested clinically. To obtain a consensus level of 100%, the last panel session was completed with a group discussion. Assessments made using the morphological criteria were compared with those made with the dental health component of the Index of Orthodontic Treatment Need. The selected morphological characteristics consisted of overjet, overbite, canine relationship, crossbite, scissors bite and midline deviation. The functional evaluation comprised assessments of discrepancy between the centric relation and the intercuspal position, working- and non-working-side contacts and protrusion contacts. The dental health component and our morphological criteria showed different sensitivity to contact point displacements, interdigitation in buccal segments and increased overbite. This study provides a set of morphological and functional indicators reflecting the current consensus opinion of Finnish professionals. Further studies are needed to analyse the reproducibility of assessment of the characteristics included.     

Expression of claudin‐11 by tumor cells in cutaneous squamous cell carcinoma is dependent on the activity of p38δ

The incidence of cutaneous squamous cell carcinoma (cSCC) is rapidly increasing, and the prognosis of patients with metastatic disease is poor. There is an emerging need to identify molecular markers for predicting aggressive behaviour of cSCC. Here, we have examined the role of tight junction (TJ) components in the progression of cSCC. The expression pattern of mRNAs for TJ components was determined with RNA sequencing and oligonucleotide array‐based expression analysis from cSCC cell lines (n=8) and normal human epidermal keratinocytes (NHEK, n=5). The expression of CLDN11 was specifically elevated in primary cSCC cell lines (n=5), but low or absent in metastatic cSCC cell lines (n=3) and NHEKs. Claudin‐11 was detected in cell‐cell contacts of primary cSCC cells in culture by indirect immunofluorescence analysis. Analysis of a large panel of tissue samples from sporadic UV‐induced cSCC (n=65), cSCC in situ (n=56), actinic keratoses (n=31), seborrhoeic keratoses (n=7) and normal skin (n=16) by immunohistochemistry showed specific staining for claudin‐11 in intercellular junctions of keratinizing tumor cells in well and moderately differentiated cSCCs, whereas no staining for claudin‐11 was detected in poorly differentiated tumors. The expression of claudin‐11 in cSCC cells was dependent on the activity of p38δ MAPK and knock‐down of claudin‐11 enhanced cSCC cell invasion. These findings provide evidence for the role of claudin‐11 in regulation of cSCC invasion and suggest loss of claudin‐11 expression in tumor cells as a biomarker for advanced stage of cSCC.     

Mortality‐risk‐based apnea–hypopnea index thresholds for diagnostics of obstructive sleep apnea

The severity of obstructive sleep apnea is clinically assessed mainly using the apnea–hypopnea index. Based on the apnea–hypopnea index, patients are classified into four severity groups: non‐obstructive sleep apnea (apnea–hypopnea index < 5); mild (5 ≤ apnea–hypopnea index < 15); moderate (15 ≤ apnea–hypopnea index < 30); and severe obstructive sleep apnea (apnea–hypopnea index ≥ 30). However, these thresholds lack solid clinical and scientific evidence. We hypothesize that the current apnea–hypopnea index thresholds are not optimal despite their global use, and aim to assess this clinical shortcoming by optimizing the thresholds with respect to the risk of all‐cause mortality. We analysed ambulatory polygraphic recordings of 1,783 patients with suspected obstructive sleep apnea (mean follow‐up 18.3 years). We simulated 79,079 different threshold combinations in 100 randomized subgroups of the population and studied the relative risk of all‐cause mortality corresponding to each combination and randomization. The optimal thresholds were chosen according to three criteria: (a) the hazard ratios increase linearly between severity groups towards more severe obstructive sleep apnea; (b) each group includes at least 15% of the study population; (c) group sizes decrease with increasing obstructive sleep apnea severity. The risk of all‐cause mortality varied greatly across simulations; the threshold defining non‐obstructive sleep apnea group having the largest effect on the hazard ratios. The apnea–hypopnea index threshold combination of 3‐9‐24 was optimal in most of the subgroups. In conclusion, the assessment of obstructive sleep apnea severity based on the current apnea–hypopnea index thresholds is not optimal. Our novel approach provides methods for optimizing apnea–hypopnea index‐based severity classification, and the revised thresholds better differentiate patients into severity groups, ensuring that an increase in the severity corresponds to an increase in the risk of all‐cause mortality.     

Impaired negative chronotropic response to adenosine in patients with inappropriate sinus tachycardia

INTRODUCTION: Adenosine is an endogenous nucleoside that has an important role in the diagnosis and treatment of several cardiac arrhythmias. However, its effects on inappropriate sinus tachycardia (IST) are not well established. METHODS AND RESULTS: In this study, the response to intravenous adenosine (0.1 to 0.15 mg/kg) was studied in 18 patients (age 46+/-15 years) with IST. In a subset of patients (n = 5), the direct effects of adenosine were assessed during pharmacologic beta-adrenergic and cholinergic blockade. Atrial cycle length (ACL) was measured before adenosine injection, at the time of the greatest cycle length prolongation, and during the maximum rebound acceleration of heart rate. Eighteen subjects (age 46+/-11 years) with normal sinus rhythm undergoing clinically indicated electrophysiologic study served as controls. Adenosine did not terminate IST in any patient. The maximum dose of adenosine prolonged the sinus interval significantly, from 780+/-128 msec to 985+/-225 msec (P < 0.001) in the control subjects. In contrast, adenosine caused no significant lengthening of atrial cycle length (527+/-69 msec vs 590+/-148 msec; P = NS) in the patients with IST. Similar difference in the response to adenosine was seen during the pharmacologic autonomic blockade. The reflex increase of the sinus rate (rebound effect) was greater in the control subjects than in the patients with IST (21.2%+/-9.7% vs 8.5%+/-8.8%; P < 0.001). CONCLUSION: The usual negative chronotropic effect of adenosine was impaired in the patients with IST. This may have important diagnostic implications and provide new insight into the mechanism(s) of IST.