Oropharyngeal squamous cell carcinoma induces an innate systemic inflammation, affected by the size of the tumour and the lymph node spread.

OBJECTIVES: Inflammation is known to be associated with the progression of cancer. The study was designed to characterise the systemic inflammation in patients with oropharyngeal squamous cell carcinoma (OPSCC) and investigate its relation to tumour size, ability to metastasise and HPV status. MATERIALS AND METHODS: Blood was obtained from 58 patients with OPSCC and 90 healthy controls and analysed with leucocyte differential count. RESULTS: The patients with OPSCC displayed an increased number of neutrophils and monocytes, whereas the lymphocytes were suppressed compared to the healthy controls. The neutrophils-to-lymphocyte ratio (NLR) and the monocyte-to-lymphocyte ratio (MLR) were calculated, and patients with large tumours exhibited high NLR and MLR. Further, patients with regional lymph node spread displayed a low NLR and MLR. Patients with HPV-positive tumours (n = 48) had a lower NLR than the patients (n = 8) with HPV-negative tumours. CONCLUSION: This study demonstrates that patients with OPSCC have an increased systemic inflammation that is affected by the HPV status, the size of the tumour and lymph node spread.

Effective dose conversion factors in paediatric interventional cardiology.

Conversion factors for effective dose (CF(E) = effective dose/dose-area product (mSv (Gy cm2)(-1)) in paediatric interventional cardiology were estimated retrospectively for 249 patients using the dose-area product (DAP), irradiation geometry, exposure parameters and tissue-weighting factors (TWFs) from the International Commission on Radiological Protection (ICRP) 60. Two methods for estimating the conversion factors, which differed in the description of the irradiation geometry, were evaluated. The effective doses obtained with the two methods were almost identical. The results showed that irradiation geometry had no significant impact on the CF(E), and a single factor was defined for both diagnostic and interventional examinations. In addition, the effect of the new tissue-weighting factor for breast tissue (TWF(b)) given in ICRP 103 on the effective dose was assessed. The CF(E) was 3.7+/-0.2 mSv (Gy cm2)(-1) (neonate), 1.9+/-0.2 mSv (Gy cm2)(-1) (1 year), 1.0+/-0.1 mSv (Gy cm2)(-1) (5 years), 0.6+/-0.1 mSv (Gy cm2)(-1) (10 years) and 0.4+/-0.1 mSv (Gy cm2)(-1) (15 years). Applying these CFs to the individual DAP values of each patient yielded mean effective doses of 13.0 mSv (neonate), 8.6 mSv (1 year), 6.4 mSv (5 years), 8.6 mSv (10 years) and 12.7 mSv (15 years). The maximum estimated skin dose (15 patients) did not exceed 60 mGy. With the new ICRP value for TWF(b), increases in the CFs in the order of 10-30%, and in the effective dose of 10-20%, were indicated. The results indicated that the effective dose in paediatric interventional cardiology is of much greater concern than the skin dose. Furthermore, age-dependent CF(E) values are required so as not to underestimate the doses to very young patients.

ECMO in ARDS: a long-term follow-up study regarding pulmonary morphology and function and health-related quality of life.

BACKGROUND: A high survival rate can be achieved in patients with severe acute respiratory distress syndrome (ARDS) using extracorporeal membrane oxygenation (ECMO). The technique and the costs are, however, debated and follow-up studies in survivors are few. The aim of this study was to evaluate long-term pulmonary health after ECMO and severe ARDS. METHODS: Twenty-one long-term survivors of severe ARDS and ECMO were studied in a follow-up program including high-resolution computed tomography (HRCT) of the lungs, extensive pulmonary function tests, pulmonary scintigraphy and the pulmonary disease-specific St George's Respiratory Questionnaire (SGRQ). RESULTS: The majority of patients had residual lung parenchymal changes on HRCT suggestive of fibrosis, but the extension of morphologic abnormalities was limited and without the typical anterior localization presumed to indicate ventilator-associated lung injury. Pulmonary function tests revealed good restitution with mean values in the lower normal range, while T(1/2) for outwash of inhaled isotope was abnormal in all patients consistent with subclinical obstructivity. Most patients had reduced health-related quality of life (HRQoL), according to the SGRQ, but were stating less respiratory symptoms than conventionally treated ARDS patients in previous studies. The majority were integrated in normal work. CONCLUSION: The majority of ECMO-treated ARDS patients have good physical and social functioning. However, lung parenchymal changes on HRCT suggestive of fibrosis and minor pulmonary function abnormalities remain common and can be detected more than 1 year after ECMO. Furthermore, most patients experience a reduction in HRQoL due to the pulmonary sequelae.

Magnetic resonance imaging and echocardiography in assessment of ventricular function in atrially corrected transposition of the great arteries.

OBJECTIVE: Patients with atrial correction of transposition of the great arteries (TGA) may develop right ventricular (RV) failure with time. A reliable non-invasive method for assessment of ventricular function is therefore needed. To evaluate the accuracy of echocardiography in assessment of ventricular volumes and function in these patients we compared echocardiography with magnetic resonance imaging (MRI) in 10 patients late after the Mustard and Senning procedures. DESIGN: Prospective echocardiography and MRI examinations were performed on the same day. Two different echocardiography technicians examined all patients. All echocardiography and MRI examinations were performed at the university hospital outpatient clinic and MRI department respectively. Ten patients, age 14.0+/-2.9 years, who had been operated on with atrial correction of TGA at 8 (2-60) months of age (median and range) were examined. Echocardiography RV and left ventricular (LV) end-systolic volumes (ESVs), end-diastolic volumes (EDVs), stroke volumes (SVs) and ejection fractions (EFs) were calculated, using the modified Simpson method, and compared with the same measurements obtained from MRI. RESULTS: For RV function there was good agreement between echocardiography- and MRI-derived measurements. Both echocardiography and MRI revealed reduced RV function with EFs of 42.6+/-9.1% and 46.4+/-7.2% respectively. For RV volumes there were no significant differences between echocardiography and MRI. LV function was significantly overestimated by echocardiography (EF with echocardiography = 72.7+/-4.4% vs. MRI = 50.5+/-7.6%) while all LV volumes were greatly underestimated. Echocardiography measurements of volumes in repeated examinations by different technicians showed large variations, 13-50%, for different variables in individual patients. CONCLUSION: Echocardiography can provide clinically important information concerning RV function in follow-up of patients late after atrial correction of TGA. It has limited value in assessment of LV function in these patients. Volume measurements by echocardiography are, however, highly user-dependent and interobserver variation is high. MRI may accordingly serve as an important reference method in individual patients.

Estimating the effective dose to children undergoing heart investigations--a phantom study.

The aim of the investigation was to assess the conversion factor (F) for derivation of effective dose from measured dose-area product (DAP) during radiological examination of congenital heart diseases. Two anthropomorphic phantoms corresponding to a 1-year-old and a 5-year-old child were irradiated at several projections to imitate irradiation conditions at heart examinations. Organ doses were measured using thermoluminescent dosimeters for calculation of mean organ doses and effective dose according to ICRP. DAP values were measured simultaneously. The conversion factor (F) was calculated from the ratio of effective dose (mSv) to DAP value (Gy cm2). The conversion factor (F) correlated strongly to the size of the phantom but less to the irradiation projection. However, at major beam angulation and at lateral projection F deviated note-worthily from that obtained at true or slightly angulated frontal views. Effective dose can therefore be estimated from the DAP values at heart investigation using two different F values. The following values are recommended for PA and lateral view respectively: for children weighing 7-11 kg, 1.8 and 1.4; for children weighing 15-26 kg 0.9 and 0.7.

Short- and long-term effects of irradiation on laryngeal mucosa of the rat.

Although radiotherapy is often used to treat laryngeal carcinoma, there is little information on the effects of this treatment on laryngeal structures. Rats were irradiated to the head and neck region and the larynges were studied by light- and electron-microscopy and immunohistochemistry. Ten days after irradiation, a change in the ultrastructural appearance of the granules of the subglottic glands was observed. Substance P-, bombesin- and enkephalin-like immunoreactivity was increased in local ganglionic cells and glandular nerve fibres. The mast cells were reduced in number. At examination 4 6 months after irradiation, there were no obvious differences compared with controls concerning mast-cell numbers and neuropeptide expression. The ultrastructural changes seen in the subglottic glands remained to some extent. The results show that structural changes in the subglottic glands occur concomitantly with an increased expression of certain neuropeptides in the innervation of these glands, which implies a relationship between these two parameters. The mast cells respond drastically to irradiation, but in the long run, regeneration of these cells occurs.

Edema formation in the rat larynx.

In the rat larynx, plasma exudation and edema formation were studied by light and electron microscopy after i.v. injections of the mast cell activator compound 48/80, substance P, and capsaicin. The morphological effects of substance P and capsaicin on connective tissue mast cells in vivo were also examined. Of the drugs tested, only compound 48/80 degranulated the connective tissue mast cells. All drugs induced a subepithelial plasma exudation in the subglottic region, with edema in the lamina propria and widened intraepithelial intercellular spaces, though the tight junction regions seemed intact. In the epiglottis, 10 min after compound 48/80 injection, there was edema in the lamina propria on the lingual side, with an intact and tight epithelial lining. No morphological sign of edema was found in the epiglottis after injection of substance P or capsaicin. The pronounced effect found in the epiglottic region after compound 48/80 injection was due to the release of mediators such as histamine and 5-hydroxytryptamine from the connective tissue mast cells. This study supports the belief that substance P in vivo mediates an increased vascular permeability by a direct effect on the blood vessels - a mechanism distinct from mast cell degranulation.

Effects of experimental Mycoplasma pulmonis infection on sensory neuropeptides and airway mucosa in the rat.

The effect of airway infection on neurogenic inflammation is not known. The present study examines the effect of Mycoplasma pulmonis infection on the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) in the trigeminal ganglion and in the mucosa of the nose and trachea in rats. We compared germ-free (GF), conventionally raised (CV) and specific pathogen-free (SPF) rats. The concentrations of SP and CGRP in the nasal mucosa were assessed with immunohistochemistry, and their prohormonal transcripts in the trigeminal ganglion were assessed with Northern blot. Mucosa was also processed for light microscopy and electron microscopy. SP-like immunoreactivity was greater in the nasal mucosa of infected animals than in uninfected controls. CGRP-like immunoreactivity was greater in the nasal septum, but not in the nasal turbinate, of infected than uninfected animals. In contrast, no change was evident in the expression levels of the prohormonal transcripts in the trigeminal ganglion. Infected nasal and tracheal mucosa was oedematous and locally infiltrated with inflammatory cells. In the nose of uninfected GF rats, subepithelial lymphoid aggregations were scarce and appeared inactive. We conclude that Mycoplasma pulmonis infection results in increased immunoreactivity of substance P, probably within nerves. There was no clear evidence of increased synthesis of the precursors of substance P and calcitonin gene-related peptide.

Foetal supraventricular tachycardia and cerebral complications.

We report on two newborn infants with foetal tachycardia and cerebral lesions. Using foetal echocardiography, the diagnosis of supraventricular tachycardia in a structurally normal heart was made at 28 and 37 weeks of gestation, respectively. One infant had a 3 week period of foetal tachycardia and hydrops before successful pharmacological cardioversion. Even several weeks after a term birth he remained hypotonic and needed gavage feeding. A computed tomography (CT) scan demonstrated cerebral lesions indicating a vascular origin. A possible thrombus was found in the heart. The other infant converted to sinus rhythm during birth by Caesarean section on the day after diagnosis. He had convulsions at the second day of life. On CT scan an infarction was found. The observations of this report suggest that cerebrovascular complications to foetal arrhythmias are more common than previously observed and should be considered when managing cases of foetal tachycardia.

Mast cells in the laryngeal mucosa of the rat. Effect of compound 48/80 and dexamethasone: a quantitative and immunohistochemical study at the light- and electron-microscopic levels.

Mucosal mast cells (MMCs) and connective tissue mast cells (CTMCs) in the epiglottic and subglottic regions in the rat larynx were characterized and quantified by immunohistochemistry and by light and electron microscopy, in control rats and rats injected intraperitoneally with dexamethasone and compound 48/80. Considerable regional differences were observed in the distribution of mast cells, especially in the epiglottis, where most cells were located on the laryngeal side. In the epithelium of the subglottic region the MMCs showed immunoreactivity for 5-hydroxytryptamine, in contrast to the epithelial MMCs in the epiglottis. In ultrathin sections, the subglottic MMCs contained larger but fewer granules compared with the epiglottic MMCs. After treatment with dexamethasone, the MMCs in the epithelium disappeared, while after treatment with compound 48/80 a large number of the CTMCs in the lamina propria became degranulated, though still present. This study shows that MMCs in the epiglottic and subglottic regions may be of two subtypes, differing in number and size of the granules as well as in chemical content.

Bombesin-like immunoreactivity in the rat larynx: increase in response to irradiation.

It is previously well known that bombesin has effects as growth factor and that changes in bombesin content in air-way structures occur in various patho-physiological conditions. In the present study, the effects of radiotherapy on bombesin expression in the rat larynx were studied. Irradiation was given for five days, 6 or 8 gray daily. Ten days after cessation of irradiation, the subglottic part of the larynx from irradiated and control animals was dissected out, and processed for immunohistochemistry or radioimmunoassay. The radioimmunoassay analysis showed that the content of bombesin-like material increased 2-fold after irradiation. The immunohistochemical analysis displayed an increased bombesin-like immunoreactivity in local ganglionic cells and in nerve fibers in the submucosal glands. These nerve fibers are likely to be derived from the local ganglionic cells. On the other hand, there was no change in the pattern of immuno-reactivity in the innervation of the epithelium and the lamina propria, including the blood vessels. The observations show that radiotherapy can be added to the list of factors that influence bombesin expression in airway structures.

Irradiation influences the expression of substance P and enkephalin in the rat larynx.

The effects of radiotherapy on neuropeptide expression in the rat larynx were studied. Irradiation was given for five days, 6 or 8 Gray daily. Ten days after the end of irradiation, the larynx, the laryngeal nerves and different ganglia related to the larynx were dissected out from irradiated and control animals and processed for neuropeptide immunohistochemistry. There was an increased immunolabelling for two of the neuropeptides tested, substance P and enkephalin, in the innervation of the subglottic glands and in the acetylcholinesterase-positive ganglionic cells of the local ganglia. These cells were interpreted as representing postganglionic parasympathetic ganglionic cells. The changes seen in the subglottic glands were interpreted as most likely being related to the changing pattern of staining seen in the local ganglia. No changes in substance P- and enkephalin expression were observed in other laryngeal structures, the nodose ganglia, superior cervical ganglia or laryngeal nerve paraganglia. Thus, in certain respects neuropeptide expression in the larynx is modulated by radiotherapy. Since neuropeptides have both neurotransmitter and/or neuromodulator effects in airway tissue and since they show effects as growth factors, the occurrence of this plasticity in neuropeptide expression should be taken into consideration in future studies examining the effects of irradiation on normal/diseased airway tissues.