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Abstract: Objective: We have previously reported that surgical removal of the nasopharyngeal adenoid in young children resulted in increased risk of nasopharyngeal colonization by pneumococci. We now investigated whether adenoidectomy influences the development of serum IgG antibodies to pneumococcal choline-binding protein A (CbpA) and pneumococcal surface protein A (PspA). Methods: Altogether 217 children aged 12–48months who had recurrent or persistent otitis media were randomized to undergo or not to undergo adenoidectomy. All the children underwent insertion of tympanostomy tubes. 166 children were followed-up for 3years. The main outcome measures were concentrations of serum IgG antibodies to CbpA and PspA three years after randomization. Nasopharyngeal colonization by pneumococci was assessed 1, 2, and 3years after randomization. Results: Adenoidectomy decreased concentrations of CbpA antibodies by ca. 25% independently of the observed increase in pneumococcal carriage (OR of log10 transformed concentrations 0.74, 95% CI 0.58–0.94, P =0.016). Concentrations of PspA antibodies were lower and they seemed not to be influenced by adenoidectomy. Conclusions: Adenoidectomy in young children causes a small but detectable impairment in the development of serum IgG antibodies to pneumococcal CbpA. The adenoid seems to have a role in augmenting systemic immunity against pneumococci. [Copyright &y& Elsevier]

Trichodysplasia spinulosa (TS)-associated polyomavirus (TSV) was recently (in 2010) discovered in TS lesions. To investigate the seroprevalence and primary exposure time of this virus, we set up a virus protein (VP1) viruslike particle (VLP)-based immunoglobulin G enzyme immunoassay. The seroprevalence of TSV was 5%, among children aged 1-4 years, rising to 48% at 6-10 years, and 70% among 149 adults. The TSV antibodies did not cross-react with corresponding Merkel cell polyomavirus VLPs, and their reactivity appeared conformational. TSV circulates widely in the human population and primary exposure is extensive in childhood, beginning at age 1-2 years. [ABSTRACT FROM AUTHOR]

Mattila PS, Hammarén-Malmi S, Tarkkanen J, Saxen H, Pitkäniemi J, Karvonen M, Tuomilehto J. Adenoidectomy during early life and the risk of asthma. Pediatr Allergy Immunol 2003: 14: 358–362. © 2003 Blackwell Munksgaard The objective of the study was to evaluate the risk of asthma in children who had undergone an adenoidectomy, an operation frequently performed on children with glue ear or recurrent otitis media. Two surveys were carried out, a nation-wide questionnaire returned by 483 individuals (survey A) and a survey of hospital discharge records involving 1616 children who had undergone an adenoidectomy and 161 control children who had undergone probing of the nasolacrimal duct due to congenital obstruction (survey B). The questionnaire (survey A) showed that an adenoidectomy before the age of 4 years was associated with asthma (OR 3.19, 95% CI 1.25; 8.13) and with allergy to animal dust (OR 2.50, 95% CI 1.27; 4.95). In survey B, asthma diagnosis was retrieved from the national asthma register. It showed also that adenoidectomy at an early age was associated with an increased risk of asthma (OR 6.74, 95% CI 2.99; 15.2). There was an association between asthma and adenoidectomy, even before adenoidectomy had actually been performed. The risk of asthma was highest among children who had had adenoidectomy because of recurrent otitis media. The observed association between an adenoidectomy and asthma may be explained by an underlying factor predisposing to both recurrent otitis media and asthma. [ABSTRACT FROM AUTHOR]

Objective: To assess the inverse association between type 1 diabetes and asthma to establish whether environmental and/or genetic factors predisposing to asthma or to atopic symptoms to inhaled antigens protect from diabetes. RESEACH DESIGN AND METHODS: Questionnaires were returned by 306 probands with childhood type 1 diabetes, their 506 nonaffected siblings, and 406 age- and sex-matched unaffected population control subjects. The main outcome measures were self-reported physician-diagnosed asthma and atopic symptoms to animal dust and pollen.Results: Risk of diabetes was inversely associated with asthma (odds ratio 0.49 [95% CI 0.24-1.00]), allergy to animal dust (0.67 [0.45-0.99]), and to a lesser degree to pollen (0.74 [0.51-1.07]) when the probands were compared with the population control subjects. Among the children of the families of an affected proband, the risk of diabetes appeared to be inversely associated with asthma (0.54 [0.27-1.09]) but not with allergy to animal dust (0.99 [0.66-1.47]) nor allergy to pollen (0.88 [0.62-1.27]).Conclusions: The frequency of asthma and atopic symptoms to some inhaled antigens is decreased in individuals with childhood type 1 diabetes. Factors predisposing to atopic symptoms to inhaled antigens may protect from childhood type 1 diabetes. [ABSTRACT FROM AUTHOR]

The presence of Epstein–Barr virus (EBV), human papilloma virus (HPV), and cytomegalovirus (CMV) was studied in 20 patients who developed malignancies after heart transplantation in the Helsinki University Central Hospital. The tumors were analyzed for the presence of HPV by polymerase chain reaction and for EBV by in situ hybridization. Clinical CMV infection was verified by immunochemical quantitation of CMV antigen in peripheral blood cells. HPV was detected in one of the eight epithelial malignant tumors studied. Three of the six lymphomas were positive for EBV. Two (67%) of 3 patients with EBV-positive lymphomas and one (33%) of the other three lymphomas but only 2 (14%) of 14 patients who developed other malignancies had a history of a manifest post-transplantation CMV infection prior to the development of malignancy. These results confirm the presence of EBV in lymphomas of heart transplant recipients and suggest that CMV might have a contributory role in the development of EBV-associated lymphomas. [ABSTRACT FROM AUTHOR]

Discusses cases of septic mediastinitis due to Mycoplasma hominis, highlighting the life-threatening nature of the infection, the tendency for pleural and pericardial effusions and the predilection for a late chronic course. Conditions of patients; Effectiveness of surgical drainage and debridement in treating mediastinitis.

Neisseria meningitidis is a causative agent of life-threatening cases of meningitis and sepsis, but it can also cause mild and self-limiting bacteraemia. Patients with N. meningitidis sepsis or meningitis often describe signs of upper respiratory tract infection before the onset of invasive disease. Viral respiratory infections have been associated with invasive meningococcal diseases and they may contribute to these prodromal symptoms. N. meningitidis can be cultivated from the throats of asymptomatic carriers and it likely enters the circulation through the upper respiratory tract. However, it is unclear whether N. meningitidis can cause simple pharyngitis. Here we describe a case of acute fulminant pharyngolaryngitis caused by N. meningitidis as verified by positive blood cultures. [ABSTRACT FROM AUTHOR]

The author reflects on treatment of chronic rhinosinusitis using antibiotics, corticosteroids and oral steroids. The author also includes different medical therapy for the diagnosis of rhinosinusitis such as saline nasal irrigation, endoscopic sinus surgery, and computed tomography scan. Various symptoms related to rhinosinusitis including nasal polyposis that sometimes occurs in conjunction with asthma and aspirin insensitivity are also discussed in the article.

The article discusses the effectiveness of antibiotics in childhood acute otitis media. Physicians often prescribe antibiotics for the condition to children despite its relatively restricted effect in treating the common condition. A recent study showed that antibiotics were beneficial for treating bilateral acute otitis media in children less than 2 years of age. Some people are concerned that reducing the use of antibiotics in treating acute otitis media could lead to mastoiditis, a rare complication that is associated with the illness. However, the research has shown no cases of mastoiditis to have occurred within the group of observed patients.

Presents a letter to the editor about the assessment of how well the objectives of undergraduate otorhinolaryngology teaching had met the professional needs of young medical doctors during their first years of work experience in Finland.

Biotin is an essential vitamin that binds streptavidin or avidin with high affinity and specificity. As biotin is a small molecule that can be linked to proteins without affecting their biological activity, biotinylation is applied widely in biochemical assays. In our laboratory, IgM enzyme immuno assays (EIAs) of m-capture format have been set up against many viruses, using as antigen biotinylated virus like particles (VLPs) detected by horseradish peroxidase- conjugated streptavidin. We recently encountered one serum sample reacting with the biotinylated VLP but not with the unbiotinylated one, suggesting in human sera the occurrence of biotin-reactive antibodies. In the present study, we search the general population (612 serum samples from adults and 678 from children) for IgM antibodies reactive with biotin and develop an indirect EIA for quantification of their levels and assessment of their seroprevalence. These IgM antibodies were present in 3% adults regardless of age, but were rarely found in children. The adverse effects of the biotin IgM on biotinylation-based immunoassays were assessed, including four inhouse and one commercial virus IgM EIAs, showing that biotin IgM do cause false positivities. The biotin can not bind IgM and streptavidin or avidin simultaneously, suggesting that these biotin- interactive compounds compete for the common binding site. In competitive inhibition assays, the affinities of biotin IgM antibodies ranged from 2.1x10-3 to 1.7x10-4 mol/L. This is the first report on biotin antibodies found in humans, providing new information on biotinylation-based immunoassays as well as new insights into the biomedical effects of vitamins. [ABSTRACT FROM AUTHOR]

Abstract: Background: Merkel cell polyomavirus (MCPyV) was identified newly (2008) and is believed to be an etiologic factor of Merkel cell carcinoma (MCC). Recent molecular and serological data suggest that MCPyV infection is common in the general population. Objectives: The aim of this study was to investigate the age of primary exposure to MCPyV. Study design: A MCPyV-IgG EIA was developed using the MCPyV major capsid protein VP1 expressed and self-assembled into virus-like particles (VLPs) in insect cells. The assay was used to detect serum IgG antibodies in two groups of children. Group 1 comprised paired and 5–8 year follow-up sera from 217 children (3–13 years) with acute lower respiratory tract infection. Group 2 comprised sera from 158 children (1–4 years) with otitis media; 86 children underwent adenoidectomy and 72 did not, whereafter follow-up sera were obtained 3 years later. Result: The prevalence of MCPyV-IgG was 9% at 1–4 years, and increased to 35% at 4–13 years among subjects from Group 1, with a 33% seroconversion rate during 5–8 years. Among Group 2, the seroconversion rate was 16% during 3 years. The IgG prevalence at 4–7 years as well as the IgG levels showed an apparent gender difference, with male preponderance prevailing among the children without adenoidectomy. Conclusion: MCPyV primary infections occur ubiquitously in childhood, and the first exposure takes place at young age. The serology showed no evidence for a causative role of MCPyV in lower respiratory tract infection manifesting as acute wheezing, but was compatible with the notion of MCPyV persistence in tonsils. [ABSTRACT FROM AUTHOR]

The association between exercise-induced bronchoconstriction (EIB) and exhaled nitric oxide (FENO) has not been investigated in young children with atopic or non-atopic wheeze, two different phenotypes of asthma in the early childhood. Steroid naïve 3- to 7-yr-old children with recent wheeze (n = 84) and age-matched control subjects without respiratory symptoms (n = 71) underwent exercise challenge test, measurement of FENO and skin prick testing (SPT). EIB was assessed by using impulse oscillometry, and FENO by standard online technique. Although FENO levels were highest in atopic patients with EIB, both atopic and non-atopic wheezy children with EIB showed higher FENO than atopic and non-atopic control subjects, respectively. In atopic wheezy children, a significant relationship between FENO and the severity of EIB was found ( r = 0.44, p = 0.0004), and FENO was significantly predictive of EIB. No clear association between FENO and EIB or predictive value was found in non-atopic wheezy children. Both atopic and non-atopic young wheezy children with EIB show increased FENO levels. However, the association between the severity of EIB and FENO is present and FENO significantly predictive of EIB only in atopic subjects, suggesting different interaction between bronchial responsiveness and airway inflammation in non-atopic wheeze. [ABSTRACT FROM AUTHOR]

Background: The etiological role of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is confirmed. However, the role of other oncoviruses in OPSCC is unknown. Materials and methods: A total of 158 consecutive OPSCC patients treated with curative intent were included. DNA extracted from tumor sections was used to detect Epstein–Barr virus (EBV), HPV, and the following polyomaviruses: John Cunningham virus (JCV), Simian virus 40 (SV40), and BK virus (BKV) with PCR. In addition, p16 expression was studied by immunohistochemistry, and EBV-encoded small RNA (EBER) transcripts were localized by in situ hybridization. The effect of viral status on overall survival (OS) and disease-free survival (DFS) was analyzed. Results: A total of 94/158 samples (59.5%) were HPV-positive, 29.1% contained BKV DNA, 20.3% EBV DNA, 13.9% JCV DNA, and 0.6% SV40 DNA. EBER was expressed only in stromal lymphocytes adjacent to the tumor and correlated with HPV positivity (p = 0.026). p16 expression associated only with HPV. None of the three polyomaviruses had an impact on survival. Patients with EBER-positive but HPV-negative OPSCC had significantly poorer OS and DFS than those with HPV-positive OPSCC and slightly worse prognosis compared with the patients with EBER-negative and HPV-negative OPSCC. Conclusion: Polyomaviruses are detectable in OPSCC but seem to have no impact on survival, whereas HPV was the strongest viral prognostic factor. EBER expression, as a sign of latent EBV infection, may have prognostic impact among patients with HPV-negative OPSCC. EBER analysis may identify a new subgroup of OPSCCs unrelated to HPV. [ABSTRACT FROM AUTHOR]

Aim: To determine if there is an association between ABO variants or blood types and otitis media. Methods: DNA samples from 214 probands from Finnish families with recurrent acute (RAOM) and/or chronic otitis media with effusion (COME) were submitted for exome sequencing. Fisher exact tests were performed when (a) comparing frequencies of ABO genotypes in the Finnish probands with otitis media vs. counts in gnomAD Finnish, and (b) within the Finnish family cohort, comparing occurrence of RAOM vs. COME according to ABO genotype/haplotype and predicted blood type. Results: Female sex is protective against having both RAOM and COME. The wildtype genotype for the ABO c.260insG (p.Val87_Thr88fs*) variant resulting in blood type O was protective against RAOM. On the other hand, type A was associated with increased risk for COME. These findings remained significant after adjustment for age and sex. Conclusions: Within the Finnish family cohort, the wildtype genotype for the ABO c.260insG (p.Val87_Thr88fs*) variant and type O are protective against RAOM while type A increases risk for COME. This suggests that the association between the ABO locus and otitis media is specific to blood type, otitis media type and cohort. [ABSTRACT FROM AUTHOR]

Background: An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC. Materials and methods: A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS). Results: High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8–117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3–57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels. Conclusion: Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients. [ABSTRACT FROM AUTHOR]

Conclusions BMI-1 is an upstream repressor of tumor suppressor p16 and their inverse expression patterns have been linked with patient survival in OPSCC. In this material only p16 remained a relevant prognostic marker in OPSCC. Objectives HNSCC tumors carry variable phenotypes and clinical outcomes depending on their anatomical location. In OPSCC, expression of tumor suppressor p16 is used as a surrogate marker of HPV infection and has prognostic value. There are no good prognostic biomarkers for HNSCC tumors of other anatomical locations. Aim To study the expression patterns of p16 and BMI-1 in not only oropharyngeal but also oral, hypopharyngeal, and laryngeal squamous cell carcinomas and to clarify their putative connections with clinical parameters, survival, and each other. Method Hospital records on 130 patients (59 OPSCC, 18 OSCC, 20 HPSCC, and 33 LSCC) diagnosed between 1997–2008 at the Helsinki University Hospital, Finland, were reviewed. BMI-1 and p16 expressions were studied by immunohistochemistry. Results Sixty-eight per cent of OPSCC expressed p16 and expression correlated with lower age, lower T- and higher N-category, and with improved OS and DFS. BMI-1 expression was most prevalent in OPSCC and LSCC, but had no clinical correlations. No correlation between p16 and BMI-1 expression was found. [ABSTRACT FROM AUTHOR]

Background: Predisposition to childhood otitis media (OM) has a strong genetic component, with polymorphisms in innate immunity genes suspected to contribute to risk. Studies on several genes have been conducted, but most associations have failed to replicate in independent cohorts. Methods: We investigated 53 gene polymorphisms in a Finnish cohort of 624 cases and 778 controls. A positive association signal was followed up in a tagging approach and tested in an independent Finnish cohort of 205 cases, in a British cohort of 1269 trios, as well as in two cohorts from the United States (US); one with 403 families and the other with 100 cases and 104 controls. Results: In the initial Finnish cohort, the SNP rs5030717 in the TLR4 gene region showed significant association (OR 1.33, P = .003) to OM. Tagging SNP analysis of the gene found rs1329060 (OR 1.33, P = .002) and rs1329057 (OR 1.29, P = .003) also to be associated. In the more severe phenotype the association was stronger. This finding was supported by an independent Finnish case cohort, but the associations failed to replicate in the British and US cohorts. In studies on TLR4 signaling in 20 study subjects, the three-marker risk haplotype correlated with a decreased TNFα secretion in myeloid dendritic cells. Conclusions: The TLR4 gene locus, regulating the innate immune response, influences the genetic predisposition to childhood OM in a subpopulation of patients. Environmental factors likely modulate the genetic components contributing to the risk of OM. [ABSTRACT FROM AUTHOR]

Extraintestinal C. difficile infections occur mainly in hospitalized patients with significant comorbidities. Most infections are localized in the abdominal area or in wounds. Mortality in these patients was high and associated with underlying diseases.Background. Clostridium difficile causes diarrhea that ranges from a benign, self-limiting antibiotic use–associated disease to a life-threatening pseudomembranous colitis. Clostridium difficile has rarely been isolated in extraintestinal infections. Our objective was to characterize clinical features and risk factors of these infections.Methods. Extraintestinal C. difficile infections (CDIs) were searched for in an electronic database of all C. difficile–positive isolates found during a 10-year period. The medical records were reviewed retrospectively. Disease severity and comorbidities of the patients were evaluated using Horn disease severity and Charlson comorbidity indexes.Results. Extraintestinal CDI was found in 31 patients who comprised 0.17% of all CDIs. Two patients had bacteremic infections, 4 had abdominal infections without any prior surgery, 7 had abdominal infections after surgery, 4 had perianal abscesses, 13 had wound infections, and 1 had C. difficile in a urinary catheter. In most cases (85%), C. difficile was isolated together with other microbes. Most (81%) patients developed the infection when hospitalized and many had severe comorbidities. Sixteen (52%) had diarrhea. The 1-year mortality rate was 36% and it correlated with the severity of underlying diseases.Conclusions. Extraintestinal CDIs occur mainly in hospitalized patients with significant comorbidities. Extraintestinal CDIs in the abdominal area may result from either intestinal perforation after infection or after intestinal surgery. Wound infections may result from colonization by feces. Clostridium difficile may reach distant sites via bacteremia. Mortality in extraintestinal CDIs is associated with the severity of underlying diseases. [ABSTRACT FROM PUBLISHER]

Conclusion: Transforming growth factor β1 gene ( TGFβ1) genotype is a potential p16 independent prognostic factor predicting response to chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC). Objectives: Expression of p16 and epidermal growth factor receptor (EGFR) has been reported to be associated with survival in HNSCC. We have previously reported that genetic polymorphism of TGFβ1 is linked with survival in HNSCC patients who have undergone chemoradiotherapy. We evaluate here whether TGFB1 genotype can serve as a prognostic factor independent of tumor p16 and EGFR expression. Methods: Expression of p16 and EGFR was studied by immunohistochemistry in tumors from 130 HNSCC patients. Peripheral blood DNA was used to genotype 95 patients for single nucleotide polymorphism rs1800470 within the TGFβ1 gene. The minimum follow-up time was 31 months. Results: p16 overexpression was associated with an improved disease-free survival (hazard ratio (HR) = 0.39, 95% CI 0.19-0.78), whereas no evident association was observed between EGFR expression and disease-free survival (HR = 0.90, 95% CI 0.68-1.19). Among the 37 patients who had received chemoradiotherapy, TGFβ1 genotype was associated with disease-free (HR = 0.44, 95% CI 0.19-1.02) and overall survival (HR = 0.31, 95% CI 0.12-0.80) independent of tumor p16 expression. [ABSTRACT FROM AUTHOR]

Summary: Cancer invasion induces extracellular matrix remodeling and collagen degradation. The aim of this study was to assess whether serum levels of type I and III collagen degradation products were associated with patient survival in head and neck squamous cell carcinoma (HNSCC). A novel enzyme immunoassay was developed for measuring type III collagen N-terminal telopeptide (IIINTP) in human serum samples. In addition, type I collagen C-terminal telopeptide (ICTP), matrix metalloprotease-8 (MMP-8) and tissue inhibitor of metalloproteases-1 (TIMP-1) were assessed in 205 blood samples from HNSCC patients. High levels of serum ICTP and IIINTP and plasma TIMP-1 were associated with poor survival. The concentration of ICTP was associated with levels of IIINTP and TIMP-1. The plasma concentration of MMP-8 was associated with tumor stage, but not with survival or levels of ICTP, IIINTP or TIMP-1 suggesting that other collagenases/proteases are responsible for the cleavage of type I and type III collagens. The rate of type I and type III collagen degradation is associated with patient survival and can be used as a prognostic marker in HNSCC. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Otitis media is a multifactorial disease where genetic background may have an important role. For genome-wide association studies, it is important to understand the degree of heritability. The objective of this study was to estimate the heritability of recurrent acute otitis media and chronic otitis media with effusion. Methods: Children operated because of recurrent or chronic otitis media at the Helsinki University Central Hospital, Finland, as well as their families were recruited during 2008–2009. A cohort of 2436 subjects was enrolled consisting of 1279 children and their parents. The study subjects answered a questionnaire concerning their otitis media history and treatment, as well as tobacco exposure, allergy and asthma history. Heritability estimates were calculated for recurrent acute, chronic and any episodes of otitis media using software especially designed for estimating heritability in family cohorts. Results: Altogether 901 subjects suffered from recurrent otitis media and 559 from chronic otitis media with effusion. The heritability estimates in our cohort were 38.5% for recurrent (P =7.3×10−9), 22.1% for chronic (P =4.6×10−3) and 47.8% for any otitis media (P =1.5×10−11). Conclusions: Our results demonstrate a moderately strong and statistically significant genetic component for both recurrent acute otitis media and chronic otitis media with effusion. These results highlight the importance of unraveling the genetic factors for otitis media that are still poorly known. [Copyright &y& Elsevier]

Conclusions: The incidence of oropharyngeal squamous cell cancer (OPSCC) in Finland has increased during the past decades. A similar change has been seen in the relative frequency of p16-positive head and neck squamous cell carcinoma (HNSCC). As p16 is a surrogate marker for human papilloma virus (HPV) infection, and as most p16-positive HNSCCs are OPSCC, HPV infection may have had a role in the observed increased incidence of OPSCC. Objectives: Numerous studies have shown that HPV is an independent risk factor for OPSCC. We aimed to use p16 as a surrogate marker of HPV infection to study its role as a possible risk factor in OPSCC. Furthermore, the change in the incidence of OPSCC in Finland was studied. Methods: HPV status was determined by p16 immunohistochemistry of 135 HNSCC tumour specimens retrieved from patients treated at the Helsinki University Central Hospital. Incidence data on OPSCC were obtained from the Finnish Cancer Registry. Results: The incidence of OPSCC in Finland increased from 0.66/100 000 person-years during 1989--1993 to 1.36 during 2004--2008. During the same period a significant increase in the relative frequency of p16 positive HNSCC tumours from 22% during 1990--1999 to 41% during 2000--2007 could be seen at our institution. In all, 85% of the p16-positive specimens were OPSCC. [ABSTRACT FROM AUTHOR]

Background: Fusobacterium species are anaerobic bacteria that relatively rarely cause sepsis with a variable clinical presentation. Methods: We reviewed the records of 52 consecutive patients who had Fusobacterium bacteraemia over a 10-y period. Results: The clinical pictures could be classified into 4 groups: (1) patients who had Lemierre's syndrome with Fusobacterium necrophorum sepsis and internal jugular vein thrombosis, n == 5 (10%); (2) previously healthy patients who had F. necrophorum sepsis without any signs of macroscopic vascular thrombosis (but 5 of them had abscesses), n == 14 (27%); (3) women who had puerperal infections, n == 6 (12%); and (4) patients who were on average older than the patients in the previous groups, who had cardiovascular, pulmonary, neoplastic, or other underlying diseases, n == 27 (52%). Of these latter 27 patients, 23 had nosocomial Fusobacterium nucleatum bacteraemia presenting as a febrile illness associated with chemotherapy or instrumentation. Conclusions: Patients with chronic underlying diseases are more likely to be infected with F. nucleatum than F. necrophorum. F. nucleatum bacteraemia may present as a febrile illness without severe symptoms. F. necrophorum caused sepsis mainly in previously healthy individuals. These infections may be accompanied with a jugular vein thrombosis characteristic of Lemierre's syndrome and septic shock. However, F. necrophorum infections present more frequently without any apparent venous thrombosis and may be accompanied by abscesses. [ABSTRACT FROM AUTHOR]

Summary: Expression of matrix metalloproteinase-8 (MMP-8) in tongue cancer cells has been associated with an improved prognosis. MMP-8 is inhibited by tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and elevated levels of TIMP-1 in blood have been associated with poor prognosis in many cancers. We wished to evaluate the usefulness of peripheral blood MMP-8 and TIMP-1 levels as well as the genotypes of MMP8 and TIMP1 in predicting prognosis in head and neck squamous cell carcinoma (HNSCC). Plasma concentrations of MMP-8 and TIMP-1 were analyzed in 136 HNSCC patients. MMP8 and TIMP1 genotypes were determined by analysis of single nucleotide polymorphisms (SNP) in peripheral blood DNA. The mean follow-up time was 3.3years. We found that plasma MMP-8 level did not predict survival but that TIMP-1 level was associated with survival. The adjusted hazard ratio of death scored as a continuous variable on the log10 scale was 23.2 (95% CI 1.88–286, P =0.01) and that of MMP-8 1.24 (95% CI 0.54–2.84, P =0.61). Immunohistochemical staining showed that TIMP-1 was expressed in vascular endothelium of tumor. TIMP-1 levels were associated with TIMP1 genotype in women but not in men. MMP8 genotype did not correlate with survival or MMP-8 level. Plasma TIMP-1 levels predict survival in HNSCC. TIMP-1 expression is genetically controlled in women. As TIMP-1 inhibits the activity of MMP-8 and it also functions as a growth factor, it may directly influence HNSCC progression. [Copyright &y& Elsevier]

Summary: Chemoradiotherapy (CRT) of head and neck squamous cell carcinoma (HNSCC) is often accompanied by severe mucosal reactions. We have recently shown that the single nucleotide polymorphism (SNP) rs1982073 of the TGFβ1 gene (TGFB1) is associated with the survival of HNSCC patients who have undergone CRT. In order to evaluate possible mechanisms mediating this, we investigated if the TGFB1 polymorphism was associated with the severity of mucositis induced by CRT. Peripheral blood DNA of 34 HNSCC patients who had undergone CRT was genotyped for the SNP rs1982073 of the TGFB1. Mucositis was graded according to acute toxicity criteria of radiation therapy oncology group (RTOG). The mean follow-up time was 48months (range, 4–115months). We did not find a significant association between the TGFB1 polymorphism and the degree of acute mucositis (OD=2.65; 95% CI 0.50–13.89; p =0.25). The degree of acute mucositis was not connected to disease-free survival (p =0.35). However, the TGFB1 polymorphism was associated with survival irrespective of the degree of mucositis (HR=3.23; 95% CI 1.19–8.77; p =0.02). [Copyright &y& Elsevier]

Conclusion. The finding of several new unique mutations suggests that the genes causing hereditary hemorrhagic telangiectasia (HHT), i.e. endoglin (ENG) and activin receptor-like kinase 1 (ACVRL1), have a relatively high mutation rate. As no single founder mutation was found, analysis of the whole coding sequences of ENG and ACVRL1 genes remains the first choice in genetic testing of new index patients with HHT. Objectives. Our aim was to characterize specific mutations causing HHT in our hospital in Helsinki serving a population of 1 million inhabitants. Patients and methods. HHT patients were searched from our hospital discharge records and their diagnoses were verified by review of patient records and interviews. Eight index patients who fulfilled HHT phenotypic criteria were tested. ENG and ACVRL1 mutations were identified by DNA sequencing of ENG and ACVRL1 coding regions. Results: Of the eight index patients, four had a mutation in the ENG gene, three in the ACVRL1 gene, and one had no mutations. All the mutations were different and all the four ENG mutations and one of the ACVRL1 mutations were new and had not been described previously in other populations. All the affected first-degree relatives had the same mutation as the index case. [ABSTRACT FROM AUTHOR]

Summary: Objective: Exposure to environmental tobacco smoke has been reported to be a risk factor for childhood otitis media. The effect of parental smoking on the risk of otitis media after the insertion of tympanostomy tubes is unknown. We evaluated the effect of parental smoking on the risk of recurrent otitis media in children who had received tympanostomy tubes. Methods: We enrolled 217 children aged 1–4 years who underwent insertion of tympanostomy tubes because of middle ear disease. The children were followed-up for 12 months. Otitis media episodes were recorded in patient diaries by primary care physicians. Parental smoking habits were assessed by a questionnaire at the start of the trial and after the 12 month follow-up had ended. The main outcome measure was risk of recurrent otitis media as defined by four or more otitis media episodes after tympanostomy. Altogether 198 children completed the follow-up. Results: Maternal smoking was associated with a highly increased risk of recurrent acute otitis media (OR 4.15, 95% CI 1.45–11.9) after the insertion of tympanostomy tubes. Conclusion: Exposure to passive smoking is associated with four-fold risk of recurrent otitis media after tympanostomy. This finding should be used to encourage parents to stop smoking even after the insertion of tympanostomy tubes to their children. [Copyright &y& Elsevier]

Conclusion: Tuberculosis is a rare disease that can mimic a neck malignancy. It should be taken into consideration when evaluating a patient with a neck mass, especially when the patient has come from an area of high endemic incidence. Another risk group comprises older people with dormant tuberculosis. Objectives: We wanted to find out the incidence of head and neck tuberculosis in Finland and to define the factors that should make one suspect it. Patients and methods: This was a retrospective analysis of patients who were diagnosed with tuberculosis in the Department of Otolaryngology, Helsinki University Central Hospital (population base c.a. 1 000 000) during 1996-2005. All the patients with culture- or PCR-positive tuberculosis were included. Results: During 1996-2005, 63 patients were diagnosed with head and neck tuberculosis, the average incidence being 0.6/100 000 per year. The age of the patients varied between 3 and 94 years (mean 47 years). The mean age of patients who were of Finnish extraction (37 patients) was 62 years and that of immigrants (26 patients) was 27 years. Forty-four (70%) patients were female and 19 (30%) male. The majority of patients presented with a neck mass without symptoms of general infection such as fever or fatigue. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the efficacy of adenoidectomy in reducing the incidence of otitis media among children who are younger than 4 years and receive tympanostomy tubes. Methods. A randomized trial was conducted at a tertiary center clinic. A total of 217 children who were aged 12 to 48 months and had recurrent acute otitis media (>3 episodes during the past 6 months) or chronic otitis media with effusion, no obstructive symptoms as a result of adenoid enlargement, and no previous surgical intervention were enrolled in the study. Adenoidectomy in conjunction with the insertion of tympanostomy tubes or insertion of tympanostomy tubes without adenoidectomy was studied. The number of otitis media episodes during the follow-up period of 12 months was measured. Results. During the follow-up, the mean number of otitis media episodes was 1.7 among children who underwent adenoidectomy with concurrent insertion of tympanostomy tubes and 1.4 among children who received tympanostomy tubes only. The risk for recurrent otitis media (≥3 episodes) could not be reduced by adenoidectomy (odds ratio: 1.66; 95%confidence interval: 0.80-3.46). Conclusion. Adenoidectomy does not significantly reduce the incidence of acute otitis media in otitis prone children who are younger than 4 years and receive tympanostomy tubes. [ABSTRACT FROM AUTHOR]

Background: Lymphoproliferative disease (PTLD) is a life-threatening complication of organ transplantation. In matched, allogeneic, non-T-cell-depleted stem-cell transplantations (SCT) the disease develops early but has been thought to be rare. Objectives: We determined by strict histopathological criteria the incidence of fatal Epstein–Barr-virus (EBV)—related PTLD in a large number of SCT, and assessed the diagnostic value of a real-time quantitative polymerase chain reaction (qPCR) for EBV-DNA in serum specimens. Study design: Of the 257 SCT performed in Helsinki during 1994–1999, 132 (51%) recipients were alive and 125 (49%) had succumbed by June 2001. The necropsies were analyzed for EBV-related PTLD as evidenced by disseminated lymphocytic infiltrates labeled histochemically for antigens and RNA (EBER 1 and 2) detectable by in situ technology. From a subset of the PTLD cases (N=12) and a series of corresponding stem-cell recipient controls (N=36), consecutive samples of serum (N=103 and 364, respectively) were studied by qPCR for EBV-DNA, and the clinical data were reviewed. Results: The post-mortem analysis revealed 18 cases of PTLD (14% of the deceased), all of whom had received intensive immunosuppressive treatment including anti-thymocyte globulin for treatment or prophylaxis of graft versus host disease (GVHD). By using qPCR all the PTLD patients became EBV-DNA positive, in progressively rising copy numbers. EBV-DNA was first detectable 70 (median; range 24–154) days after SCT or 23 (4–86) days before death; i.e. earlier than the symptoms which appeared 15 (2–85) days before death. Among the SCT controls, EBV-DNA occurred sporadically (in only 3.9% sera). Conclusions: qPCR for EBV-DNA in serum is a highly sensitive (100%) and specific (96%) diagnostic approach. Intensely immunosuppressed stem-cell recipients are at a great risk of developing PTLD, and should be carefully monitored for EBV-DNA, for pre-emptive treatment of this life-threatening disorder. [Copyright &y& Elsevier]

In oropharyngeal squamous cell carcinoma (OPSCC), the expression pattern of toll-like receptors (TLRs), in comparison between human papillomavirus (HPV)-positive and -negative tumors differs. TLRs control innate immune responses by activating, among others, the nuclear factor-κΒ (NF-κΒ) signaling pathway. Elevated NF-κΒ activity is detectable in several cancers and regulates cancer development and progression. We studied TLR5 expression in 143 unselected consecutive OPSCC tumors, and its relation to HPV-DNA and p16 status, clinicopathological parameters, and patient outcome, and studied TLR5 stimulation and consecutive NF-κB cascade activation in vitro in two human OPSCC cell lines and immortalized human keratinocytes (HaCat). Clinicopathological data came from hospital registries, and TLR5 immunoexpression was evaluated by immunohistochemistry. Flagellin served to stimulate TLR5 in cultured cells, followed by analysis of the activity of the NF-κB signaling cascade with In-Cell Western for IκΒ and p-IκΒ. High TLR5 expression was associated with poor disease-specific survival in HPV-positive OPSCC, which typically shows low TLR5 immunoexpression. High TLR5 immunoexpression was more common in HPV-negative OPSCC, known for its less-favorable prognosis. In vitro , we detected NF-κΒ cascade activation in the HPV-positive OPSCC cell line and in HaCat cells, but not in the HPV-negative OPSCC cell line. Our results suggest that elevated TLR5 immunoexpression may be related to reduced NF-κΒ activity in HPV-negative OPSCC. The possible prognosis-worsening mechanisms among these high-risk OPSCC patients however, require further evaluation. • High TLR5 expression was associated with poor DSS in HPV-positive OPSCC, typically showing low TLR5 immunoexpression. • High TLR5 immunoexpression was more common in HPV-negative OPSCC, known for its less-favorable prognosis. • In vitro stimulation of TLR5 with flagellin activated the NF-kB cascade in HPV-positive OPSCC cells and in HaCat cells. • No activation of the NF-kB cascade by TLR5 stimulation in HPV-negative OPSCC cells occurred. • Elevated TLR5 immunoexpression may be related to reduced NF-kB activity in HPV-negative OPSCC. [ABSTRACT FROM AUTHOR]

Presents a response by Sari Hammarén-Malmi, et al to a letter to the editor about their study on adenoidectomy and tympanostomy.