Absence of high-risk human papilloma virus in p16 positive inverted sinonasal papilloma.

OBJECTIVES: Sinonasal inverted papilloma (SIP) is a relatively rare disease, and its etiology is not understood. It is characterized by locally aggressive growth and a strong tendency to recur despite its benign histology. AIMS: The aim of this study was to identify the presence of human papilloma virus (HPV) and its surrogate marker p16 in SIP tissue samples from a regional cohort. MATERIAL AND METHODS: Subjects were identified from our regional center cohort of 88 SIP patients treated between 1984-2014. From these subjects, 54 were included in this study. Of these, 53 biopsies were analyzed with PCR, and 54 samples were immunohistochemically stained for p16. DNA was extracted from histopathologically verified SIP. Genotype screening for 13 high risk-, 5 oncogenic and 6 low risk HPV types was performed using the PapilloCheck® HPV-screening test. RESULTS: HPV analysis was successful for 38 of 53 samples. Of the 38 successfully analyzed samples, only 2 samples were positive for HPV 11. Notably, p16 was present in the epithelia in all samples, and in the papilloma lesions in 37 samples. CONCLUSION: Since only 2 out of 38 SIPs were positive for HPV (type 11), and at the same time p16 was positive in epithelia in all samples and in 37 of 38 papilloma lesions of the samples, it is concluded that p16 cannot be used as a surrogate marker for high-risk HPV-infection in SIP. We are currently planning a prospective, multicenter study in order to increase the study power and in order to be able to better evaluate the clinical implications of HPV-and p16 in SIP.

Acoustic formation of multicellular tumor spheroids enabling on-chip functional and structural imaging.

Understanding the complex 3D tumor microenvironment is important in cancer research. This microenvironment can be modelled in vitro by culturing multicellular tumor spheroids (MCTS). Key challenges when using MCTS in applications such as high-throughput drug screening are overcoming imaging and analytical issues encountered during functional and structural investigations. To address these challenges, we use an ultrasonic standing wave (USW) based MCTS culture platform for parallel formation, staining and imaging of 100 whole MCTS. A protein repellent amphiphilic polymer coating enables flexible production of high quality and unanchored MCTS. This enables high-content multimode analysis based on flow cytometry and in situ optical microscopy. We use HepG2 hepatocellular carcinoma, A498 and ACHN renal carcinoma, and LUTC-2 thyroid carcinoma cell lines to demonstrate (i) the importance of the ultrasound-coating combination, (ii) bright field image based automatic characterization of MTCS, (iii) detailed deep tissue confocal imaging of whole MCTS mounted in a refractive index matching solution, and (iv) single cell functional analysis through flow cytometry of single cell suspensions of disintegrated MTCS. The USW MCTS culture platform is customizable and holds great potential for detailed multimode MCTS analysis in a high-content manner.

Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-1.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased. METHODS: Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry. RESULTS: No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC. CONCLUSION: Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged ⩽40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair.

Level of physical activity associated with risk of cardiovascular diseases and mortality in patients with type-2 diabetes: report from the Swedish National Diabetes Register.

AIMS: To estimate risks of coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality with low or higher levels of physical activity (PA) assessed with questionnaire, in an observational study of patients with type-2 diabetes from the Swedish National Diabetes Register. SUBJECTS AND METHODS: A total of 15,462 patients (60 years), were followed for 5 years from baseline in 2004 until 2009, with 760 CVD events and 427 total mortality events based on 54,344 person-years. RESULTS: Comparing 6963 patients with low baseline PA (never or 1-2 times/week for 30 min) and 8499 patients with higher baseline PA (regular 3 times/week or more), hazard ratios for fatal/nonfatal CHD, fatal/nonfatal CVD, fatal CVD, and total mortality were 1.25 (95% CI 1.05-1.48; p = 0.01), 1.26 (95% CI 1.09-1.45; p = 0.002), 1.69 (95% CI 1.18-2.41; p = 0.004), and 1.48 (95% CI 1.22-1.79; p < 0.001), adjusting for age, sex, diabetes duration, diabetes treatment, and smoking (model 1). Adjusting also for HbA1c, systolic blood pressure, low- and high-density lipoprotein cholesterol, triglycerides, body mass index, and albuminuria (model 2), HRs were 1.19 (95% CI 1.00-1.42; p = 0.049), 1.18 (95% CI 1.02-1.36; p = 0.04), 1.54 (95% CI 1.07-2.22; p = 0.02), and 1.41 (95% CI 1.16-1.72; p < 0.001), respectively. Corresponding results (model 2), comparing 4166 patients having low PA both baseline and at follow up with all other 11,296 patients were 1.68 (95% CI 1.41-2.01), 1.68 (95% CI 1.45-1.96), 2.12 (95% CI 1.48-3.03), and 2.03 (95% CI 1.66-2.48) (all p < 0.001) and compared to 2797 patients with low baseline PA and higher PA at follow up were 2.51 (95% CI 1.87-3.38), 2.54 (95% CI 1.98-3.27), 3.26 (95% CI 1.74-6.10), and 2.91 (95% CI 2.08-4.07) (all p < 0.001). CONCLUSIONS: This large observational study of patients with type-2 diabetes showed considerably increased risks for CVD and mortality with low PA.

Deep brain stimulation - effects on swallowing function in Parkinson's disease.

OBJECTIVE: In patients with Parkinson's disease (PD), deep brain stimulation of the subthalamic nucleus (STN DBS) is well recognized in improving limb function, but the outcome on swallowing function has rarely been studied. The aim of this work was to evaluate the effect of STN DBS on pharyngeal swallowing function in patients with PD using self-estimation and fiberoptic endoscopic evaluation of swallowing. METHODS: Eleven patients (aged 41-72, median 61 years) were evaluated preoperatively and at 6 and 12 months after STN DBS surgery. All patients were evaluated with self-estimation on a visual analogue scale, and eight of them with a fiberoptic endoscopic examination with a predefined swallowing protocol including Rosenbek's Penetration-Aspiration Scale, Secretion Severity Scale, preswallow spillage, pharyngeal residue, and pharyngeal clearance. RESULTS: The self-assessments of swallowing function revealed a subjective improvement with STN DBS stimulation, whereas the data from the swallowing protocol did not show any significant effect of the STN DBS treatment itself. The prevalence of aspiration was not affected by the surgery. CONCLUSIONS: The results show that swallowing function was not negatively affected by STN DBS and the risk of aspiration did not increase. Self-estimation of swallowing function showed a subjective improvement due to stimulation.

Swallowing function in Parkinson's patients following Zona Incerta deep brain stimulation.

OBJECTIVE: The purpose of the present study was to examine whether there was a negative effect of caudal Zona Incerta deep brain stimulation (cZI DBS) on pharyngeal swallowing function in Parkinson's patients (PD). There are no former reports including swallowing and cZI DBS. METHODS: Eight patients (aged 49-71 years; median 62) were evaluated pre- and post-operatively, at 6 and 12 months after DBS surgery. Evaluation tools were fiberoptic endoscopic evaluation of swallowing examinations and patients' self-assessments of their swallowing function including a visual analog scale and quality-of-life-related questions. The swallowing protocol included Rosenbek's Penetration-Aspiration Scale, Secretion Severity Scale and parameters for preswallow spillage, pharyngeal residue, and pharyngeal clearance. RESULTS: There was no clear-cut effect of neurostimulation post-operatively at 6 and 12 months on any of the swallowing parameters except for the preswallow spillage that was slightly worsened in the stimulation on condition 12 months post-operatively. The answers to the self assessment questions did not vary significantly. CONCLUSIONS: The effect of the stimulation on the swallowing function varied among individuals, but the overall outcome was that cZI DBS did not seem to have a negative influence on swallowing function in the eight patients studied.

Risk of cardiovascular disease and mortality in overweight and obese patients with type 2 diabetes: an observational study in 13,087 patients.

AIMS/HYPOTHESIS: The aim of this study of type 2 diabetic patients in the Swedish National Diabetes Register was to study the associations of BMI, overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI >or= 30 kg/m(2)) with cardiovascular disease in type 2 diabetes, as these associations have not previously been clarified. METHODS: Patients aged 30-74 years with no previous CHD or stroke (N = 13,087) were followed for a mean of 5.6 years until 2003 for fatal or non-fatal CHD, stroke, cardiovascular disease (CHD or stroke) and total mortality. In total, 1,922 cardiovascular-disease events occurred, based on 64,864 person-years. RESULTS: The relative risks of CHD, stroke, cardiovascular disease and total mortality for a 5 unit increase in BMI at baseline were 15%, 11%, 13% and 27%, respectively, using Cox regression analysis, after adjusting for age, sex, diabetes duration, hypoglycaemic treatment and smoking (model 1), and were 9%, 4% (not significant), 7% and 20%, respectively, when adjusting also for HbA(1c), blood pressure, antihypertensive drugs, lipid-reducing drugs and microalbuminuria (model 2). Adjusted hazard ratios (model 1) for CHD, cardiovascular disease and total mortality with overweight were 1.27 (95% CI 1.09-1.48), 1.24 (1.09-1.41) and 1.16 (0.94-1.45), respectively, and 1.49 (1.27-1.76), 1.44 (1.26-1.64) and 1.71 (1.36-2.14) with obesity, as compared with normal weight. Significant hazard ratios were attenuated when adjusted according to model 2. For a 1 unit increase in BMI during follow-up, the relative risk of CHD (model 2) was 1.13 (1.04-1.23; p = 0.005). CONCLUSIONS/INTERPRETATION: Both overweight and obesity independently increased the risk of CHD and cardiovascular disease in patients with type 2 diabetes. The CHD risk was higher with increasing BMI than with stable or decreasing BMI during the study.

Antihyperglycaemic treatment of type 2 diabetes: results from a national diabetes register.

AIM: To describe clinical characteristics and antihyperglycemic treatment patterns in patients with varying duration of diabetes. METHODS: We performed a cross-sectional survey of 61890 type 2 diabetic (DM2) patients from the Swedish National Diabetes Register (NDR) in 2004. We also analysed the effect of types of treatment and risk factors on glycaemic control in a longitudinal cohort study from 1996 to 2004. HbA(1c), risk factors and treatments were determined locally in primary care as well as hospital outpatient clinics. RESULTS: Insulin was frequently used in DM2 patients with long duration of diabetes, although the mean HbA(1c) increased and only a few in this group reached HbA(1c) <7.0%. Patients showing long-term improvement in HbA(1c) (>1%) from 1996 to 2004 were more often treated with insulin than with oral hypoglycaemic agents (OHA). During this period, the HbA(1c) levels leading to additional treatment decreased. A low BMI, decreasing BMI and not smoking were predictors of good long-term metabolic control. Hypertension and hyperlipidaemia were frequent in both newly diagnosed DM2 patients and in patients with a long duration of diabetes. CONCLUSIONS: Insulin treatment was frequently used, particularly in patients with a long duration of DM2. The glycaemic control, which usually deteriorates over time, did not reach the recommended goal, despite the fact that complementary treatment was added at lower HbA(1c) levels in 2003 than in 1996. High frequencies of hypertension, hyperlipidaemia and high 10-year risks of coronary heart disease necessitate intensified risk factor control in the future.

Randomized clinical trial comparing conservative and surgical treatment of neurogenic faecal incontinence.

BACKGROUND: The treatment of choice in idiopathic (neurogenic) faecal incontinence is controversial. In a randomized study levatorplasty was compared with anal plug electrostimulation of the pelvic floor with respect to functional outcome and physiological variables. METHODS: Thirty-one patients underwent levatorplasty and 28 anal plug electrostimulation of the pelvic floor over 3 years. The results were evaluated at 3, 12 and 24 months after completion of treatment by means of a validated questionnaire and anorectal manometry and manovolumetry. RESULTS: Incontinence scores were significantly reduced during the entire observation period in both groups (P < 0.001) as was the use of pads (P = 0.003 to P < 0.001). The proportion of patients reporting improvement in physical and social handicap was greater in the levatorplasty group after 3, 12 and 24 months (P = 0.036 to P < 0.001). No significant changes in physiological variables were observed in either group. CONCLUSION: Better results were obtained with levatorplasty than with anal plug electrostimulation of the pelvic floor in patients with idiopathic (neurogenic) faecal incontinence. Levatorplasty should be therefore be considered the treatment of choice for this condition.

Neuro-ophthalmologic findings in konzo, an upper motor neuron disorder in Africa.

PURPOSE: To investigate the neuro-ophthalmological manifestations in konzo, a non-progressive symmetric spastic para/tetraparesis of acute onset associated with consumption of insufficiently processed bitter cassava roots combined with a low protein intake. METHODS: Twenty-one Congolese konzo patients underwent neuro-ophthalmological investigations including visual acuity testing, assessment of light pupillary reflexes, evaluation of ocular motility and deviation, direct ophthalmoscopy, and visual field perimetry. Objective refraction including retinoscopy and keratometry, and slit-lamp biomicroscopy were also done. RESULTS: Five patients had visual impairment, and 14 had temporal pallor of the optic disc. Fourteen presented visual field defects, the most frequent being concentric constriction and peripheral defects. Overall, 11 subjects had symptoms qualifying for the diagnosis of optic neuropathy. Two had spontaneous pendular nystagmus in primary position of gaze. Visual field defects and pallor of the optic discs were found in mild, moderate and severe forms of konzo. No correlation was found between the severity of the motor disability of konzo and the extent of visual field loss. CONCLUSIONS: Konzo was associated with optic neuropathy and a few patients had nystagmus. Although the etiopathogenesis of this optic neuropathy remains to be elucidated, the symmetry of the involvement suggests a toxic origin. We suggest that cyanide causes the neuro-ophthalmological damage in konzo. However, the optic neuropathy in konzo patients does not resemble the features of the epidemic optic neuropathy in Tanzania, Cuba or Nigeria, Leber's hereditary optic neuropathy, tobacco amblyopia or vitamin B deficiency.

Diagnostic assessment of haemorrhagic rash and fever.

AIMS: To establish criteria for early distinction between meningococcal disease and other conditions with similar clinical features, and to identify other causes for haemorrhagic rashes accompanied by fever. METHODS: In a prospective study, 264 infants and children hospitalised with fever and skin haemorrhages were studied. RESULTS: We identified an aetiological agent in 28%: 15% had meningococcal disease, 2% another invasive bacterial infection, 7% enterovirus infection, and 4% adenovirus infection. Five clinical variables distinguished between meningococcal disease and other conditions on admission: (1) skin haemorrhages of characteristic appearance; (2) universal distribution of skin haemorrhages; (3) maximum diameter of one or more skin haemorrhages greater than 2 mm; (4) poor general condition (using a standardised observation scheme); and (5) nuchal rigidity. If any two or more of these clinical variables were present, the probability of identifying a patient with meningococcal disease was 97% and the false positive rate was only 12%. This diagnostic algorithm did not identify children in whom septicaemia was caused by other bacterial species.

Parkinsonism and neck extensor myopathy: a new syndrome or coincidental findings?

BACKGROUND: Dropped head in parkinsonism has been attributed to dystonia or unbalanced muscle rigidity. To our knowledge, isolated neck extensor myopathy with parkinsonism has been described in only one patient. OBJECTIVES: To assess the occurrence of neck extension weakness resulting in dropped head in patients with parkinsonism and to explore whether the head drop might be the consequence of neck extensor myopathy. PATIENTS AND METHODS: All patients who were evaluated because of parkinsonism in the Department of Neurology in our hospital between January 1, 1997, and December 31, 1999, and were found to have both parkinsonism and neck extension weakness resulting in head drop were studied. The patients underwent clinical examination, blood tests including the levels of creatine kinase and myoglobin and neurophysiological evaluation with needle electromyography and autonomic tests. Open biopsy on a neck muscle was performed in the patients who could cooperate. RESULTS: Of 459 patients evaluated because of parkinsonism, 7 were found to have neck extensor weakness resulting in head drop. Needle electromyography revealed myopathic changes in all 7 patients. Muscle biopsy, which was performed in 5 patients, disclosed myopathic changes in all 5 patients. Electron microscopy revealed mitochondrial abnormalities in 2 of these 7 patients. Three of the patients had concomitant neck rigidity that could contribute to the neck position. All 7 patients had autonomic dysfunction and 6 responded poorly to levodopa therapy, making a diagnosis of multiple system atrophy probable. CONCLUSION: Parkinsonism may be associated with isolated neck extensor myopathy resulting in dropped head, and this condition should be suggestive of multiple system atrophy.

Results of surgical treatment for faecal incontinence.

BACKGROUND: This prospective study was designed to evaluate the results of anterior levatorplasty and sphincteroplasty for faecal incontinence with respect to symptomatic and physiological outcome. METHODS: Thirty-one patients with idiopathic (neurogenic) faecal incontinence underwent anterior levatorplasty and 20 patients with traumatic anal sphincter injury underwent anal sphincteroplasty. The outcome of repair was evaluated at 3 and 12 months using a validated questionnaire and anorectal manometry/manovolumetry. RESULTS: Eighteen of 31 patients in the levatorplasty group reported continence to solid and liquid stools 1 year after operation compared with two patients before surgery (P < 0.01). The corresponding figures in the sphincteroplasty group were ten and two of 20 respectively (P < 0.05). The incontinence score was improved in both groups after 1 year, from a median score of 14 to 3 in the levatorplasty group (P < 0.001) and from 8.5 to 3.5 in the sphincteroplasty group (P < 0.01). Improvements in the degree of social and physical handicap were also observed in both groups. No changes were seen in anal canal pressures or rectal sensation in either group. CONCLUSION: Despite different aetiologies and surgical approaches, anterior levatorplasty and sphincteroplasty yielded similarly successful results in patients with faecal incontinence. Although a marked symptomatic improvement was seen in both groups, no associated physiological alterations could be detected. The reason for the improvement is thus unclear, but it may result from a stenosing effect in the anal canal.

Human uvula: characterization of resident leukocytes and local cytokine production.

Upper airway infections often lead to macroscopic changes in the architecture of the uvula. Using immunomorphometric analysis, we investigated the frequency and distribution of immune cells and of cytokine-producing cells in uvular samples. Tissue macrophages, alphabeta T cells, gammadelta T cells, and B cells were, in declining order, the main cell populations. Gammadelta T cells and B cells exhibited reciprocal localization, with almost all gammadelta T cells residing in the vicinity of the epithelium, and all B cells in the glandular area. The presence of cells expressing the suppressor phenotype CD8+CD28- alphabeta T cells is suggested. Fifteen to twenty-five percent of the immune cells expressed the down-regulatory cytokine tumor growth factor beta. Most macrophages were located subepithelially, in the vicinity of the basal lamina. The composition and cytokine profile of leukocytes in the tissue suggest that the uvula may be a site, additional to the jejunal mucosa, for induction of mucosal tolerance to inhaled and ingested antigens. Concomitantly, the uvula appears to be protected from invasion of microbial pathogens by a subepithelial barrier of macrophages and gammadelta T cells.

Structure of the human uvula.

Eleven uvular biopsies were investigated for their morphology, the presence of mast cells and the distribution of hyaluronan and its major ligand CD44. Three microanatomical sites--surface epithelium, subepithelial area and area of glands--were examined. The oral side of the uvula was covered by a 15-20 cell thick layer of keratinized/parakeratinized surface epithelium, firmly anchored to the underlying connective tissue by connective tissue papillae. The width of the intercellular spaces in the epithelium increased toward the basal lamina, a location that exhibited intense hyaluronan and anti-CD44 staining. Most mast cells were located in the vicinity of blood vessels, at which sites there was high staining intensity of hyaluronan. Tissue mast cells could also be observed in the connective tissue septa enclosing the acini. Glands and muscle fibres became more sparse from the proximal part of the uvula to the distal end, while the amount of connective tissue increased. The localization and architecture of connective tissue elements and mast cells are consistent with the ability of the uvula to resist mechanical stresses and to develop oedema and fibrosis, respectively.

Is electrostimulation of the pelvic floor an effective treatment for neurogenic faecal incontinence?

BACKGROUND: This study was designed to evaluate the results of electrostimulation of the pelvic floor for faecal incontinence. METHODS: Twenty-four patients with neurogenic (n = 20) or idiopathic (n = 4) incontinence were treated on 12 occasions. Twenty were women, and the mean age was 63 years (range, 26-85 years). The result was evaluated at 3 and 12 months with a validated questionnaire and anorectal manometry. RESULTS: Eleven patients (46%) reported improvement after 3 months, and the Miller's incontinence score was reduced (P < 0.01). Resting pressures, rectal compliance, and the length of the high-pressure zone were unchanged, but squeeze pressures tended to decrease. A lower threshold was seen for the rectoanal inhibitory reflex (RAIR) (P < 0.01), and the saline infusion test tended to show improved retention (P = 0.07). Nine of 13 patients followed up for 1 year claimed improvement. The most pronounced subjective improvement was seen in patients with moderate incontinence. CONCLUSIONS: Electrostimulation was successful in a substantial proportion of the patients. The threshold for RAIR was lowered, and the saline infusion test tended to improve, but variables reflecting sphincter competence did not improve. Moderate incontinence was prognostically favourable, and electrostimulation might therefore be an alternative to surgery in this group.

Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy linked to chromosome 10q.

Twenty-one members of a Swedish family suffering from myopathy and cardiomyopathy underwent neurological and cardiological investigations. Medical charts of 2 affected deceased patients were reviewed. Twelve patients had myopathy. The distribution of weakness was axial in mildly affected, axial and predominantly distal in moderately affected, and generalized in severely affected patients. The electromyogram showed signs of myopathy in 10 patients. Muscle biopsy specimens showed myopathic changes, rimmed vacuoles, and accumulation of desmin, dystrophin, and other proteins. Electron microscopy revealed granulofilamentous changes and disorganization of myofibrils. Several patients had episodes of chest pain or palpitations. Three men had arrhythmogenic right ventribular cardiomyopathy. Nonsustained ventribular tachycardia, atrial flutter, and dilatation of the ventricles mainly affecting the right ventricle were documented. Two of them had a pacemaker implanted because of atrioventricular block and sick sinus syndrome. Inheritance is autosomal dominant with variable onset and severity of skeletal muscle and cardiac involvement. Linkage analysis of candidate chromosomal regions showed a maximum 2-point LOD score of 2.76 for marker locus D10S1752 on chromosome 10q. A multipoint peak LOD score of 3.06 between markers D10S605 and D10S215 suggests linkage to chromosome 10q22.3, and this region may harbor a genetic defect for myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopahty.

Epidemiology of respiratory syncytial virus infection requiring hospitalization in East Denmark.

BACKGROUND: Prophylaxis against infection caused by respiratory syncytial virus (RSV) with high titered RSV immunoglobulin or humanized antibody may soon be available in Europe. OBJECTIVE: To study the epidemiology of RSV infections requiring hospitalization in infants <6 months in East Denmark to provide a rational basis for decisions concerning prophylaxis against RSV. METHOD: Populat ion-based retrospective review of case records of infants <6 months admitted to pediatric departments with RSV infection in East Denmark from November 1, 1995, to April 30, 1996. RESULTS: Data were obtained from 459 infants. Seventy-three had predisposing conditions: prematurity, 49; pulmonary disease, 2; congenital heart disease, 7; neurologic disease, 6; others, 9. One preterm infant had bronchopulmonary dysplasia. The incidence of RSV infection requiring hospitalization in East Denmark among infants <6 months was estimated to be 34/1000/season. It was 32/1000/season among term infants and 66/ 1000/season among preterm infants (P<0.001). Infants with predisposing conditions and/or nosocomial infection (n = 24) had significantly more severe courses than otherwise healthy infants (P<0.01). One-hundred thirty infants received respiratory support by nasal continuous positive airway pressure, but only six required mechanical ventilation. No infants died. CONCLUSION: The course of RSV disease in East Denmark was milder than reported elsewhere, possibly as a result of the low prevalence of bronchopulmonary dysplasia in Denmark. However, RSV constitutes a considerable burden to the Danish pediatric health care system, and therefore prophylaxis against RSV is desirable.

The surface epithelium of recurrent infected palatine tonsils is rich in gammadelta T cells.

Using a large panel of MoAbs in quantitative morphometric analysis of immunohistochemically stained tissue sections, we compared the frequency and distribution of immune cells in palatine tonsils from patients with recurrent tonsillitis (RT) and patients with idiopathic tonsillar hypertrophy (ITH). We found that differences between the two patient groups in leucocyte populations were limited to the surface epithelium, whereas the cellular composition of interfollicular and follicular areas was similar. Most intraepithelial lymphocytes were CD8+ T cells in both groups. However, the number of intraepithelial T cells was significantly higher in RT compared with ITH. This was due to a selective increase in the number of intraepithelial CD8+ gammadelta T cells utilizing Vdelta1 and Vgamma9. In both patient groups the majority of the intraepithelial gammadelta T cells expressed Vdelta1 and Vgamma9. Subepithelially, gammadelta T cells utilizing Vgamma9 dominated over cells utilizing Vgamma8, while equal proportions expressed Vdelta1 and Vdelta2. These results suggest that cells utilizing the otherwise rare combination Vdelta1/Vgamma9 in their T cell receptors (TCR) may constitute a major gammadelta T cell population in palatine tonsils and are probably reactive to antigens specific to the tonsillar milieu. Furthermore, they indicate that preferentially this gammadelta T cell subpopulation is involved in immune reactions within the surface epithelium in RT. We speculate that gammadelta T cells are involved in clearing infectious bacteria at the tonsillar surface and in limiting inflammatory responses in the tonsils. Both local expansion and infiltration of blood cells probably contribute to the high numbers of gammadelta T cells in RT patients.

Abundance of intraepithelial gamma delta T cells in hypertrophic obstructive but not in chronically infected adenoids.

Using quantitative morphometric analysis of immunohistochemically stained tissue sections we compared hypertrophic obstructive adenoids (HOA, n = 10) from children without middle ear disease with chronically infected adenoids (CIA, n = 10) from children with middle ear disease. gamma delta T cell receptor (TCR)+ cells constituted the dominating T cell population in the surface epithelium of HOA, while alpha beta TCR+ cells were the dominating intraepithelial T cell population in CIA. Intraepithelially CD8+ cells dominated over CD4+ cells in both diseases. Intraepithelially B cells were not detected. The cellular composition of follicles, with B cells dominating followed by activated CD4+ alpha beta TCR+ cells, was the same in both groups. However, the number of follicles in CIA was twice as many as in HOA. In the deeper interfollicular areas granulocytes were more abundant in CIA than in HOA. The latter two findings suggest a more pronounced inflammatory response in the adenoids of patients with middle ear disease. There was no significant difference with regard to pathogenic bacterial strains colonizing the adenoid surface when comparing the two patient groups. These results suggest that in patients with HOA gamma delta TCR+ T cells help to maintain the integrity of the surface epithelium, thereby preserving its protective function. On the basis of our results we speculate that CIA have a malfunctioning defence, thereby facilitating long-standing infections deep in the adenoid. This may be the main reason for development of middle ear disease and an indication for adenoidectomy in patients with CIA.