Association of the -14C/G MET and the -765G/C COX-2 gene polymorphisms with the risk of chronic rhinosinusitis with nasal polyps in a Polish population

Chronic rhinosinusitis with nasal polyps is strongly associated with other diseases, including asthma and allergy. The following study tested the association of the -765 G/C polymorphism of cyclooxygenase-2 (COX-2) encoding gene and the -14C/G polymorphism of protooncogen MET (MET) encoding gene with a risk of chronic rhinosinusitis with nasal polyps in a Polish population. One hundred ninety-five patients of chronic rhinosinusitis with nasal polyps as well as 200 sex-, age-, and ethnicity-matched control subjects without chronic sinusitis and nasal polyps were enrolled in this study. Among the group of patients, 63 subjects were diagnosed with allergy and 65 subjects with asthma, respectively. DNA was isolated from peripheral blood lymphocytes of patients as well as controls, and gene polymorphisms were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Ten percent of the samples have been confirmed by a second method single-strand conformation polymorphism (SSCP)-PCR. We reported that the -765 G/C COX-2 (odds ratio [OR] 7.79; 95% confidence interval [CI] 4.88-12.4, p<0.001) and the -14C/G MET (OR 2.83; 95% CI 1.74-4.61, p<0.001) were associated with an increased risk of chronic rhinosinusitis with nasal polyps among analyzed group of patients. Moreover, the group of patients without allergy or asthma indicated the association of the -765 C/G (OR 7.25; 95% CI 4.38-12.1, p<0.001 and OR 7.61; 95% CI 4.47-12.6, p<0.001) genotype of the COX-2 as wells as the -14C/G (OR 2.47; 95% CI 1.46-4.17, p<0.001 and OR 2.59; 95% CI 1.54-4.37, p<0.001) genotype of MET with an increased risk of chronic rhinosinusitis with nasal polyps. Finally, it was also found that the selected group of patients with allergy or asthma indicated a very strong association of the -765 G/C (OR 5.64; 95% CI 2.91-10.9 and OR 4.74; 95% CI 2.49-9.03, p<0.001, respectively) genotype of the COX-2 with an increased risk of chronic rhinosinusitis with nasal polyps. Thus, our results suggest that COX-2 and MET gene polymorphisms may have deep impact on the risk of rhinosinusitis nasal polyp formation, which may also depend on asthma or allergy. Our results showed that the -765 G/C polymorphism of COX-2 gene and the -14C/G polymorphism of the MET gene may be associated with the risk of chronic rhinosinusitis with nasal polyps in a Polish population.     

Levels of antibodies to microorganisms implicated in atherosclerosis and of C-reactive protein among atomic bomb survivors

Although it has been suggested that cardiovascular disease incidence is increased among atomic bomb survivors, the existence of a causal relationship between radiation exposure and atherosclerosis is unclear. Microbial infections, including those caused by Chlamydia pneumoniae, Helicobacter pylori and cytomegalovirus, have recently been implicated in atherosclerosis. Since immune function is somewhat impaired among atomic bomb survivors, their immune defense against such infections might be diminished. To investigate this possibility, we measured antibody levels to the above microorganisms in the sera of survivors. We found that the levels of IgG and IgA antibodies to Chlamydia pneumoniae decreased significantly with radiation dose, whereas the levels of IgG antibodies to Helicobacter pylori or cytomegalovirus remained unchanged. The inflammation marker C-reactive protein was significantly and positively associated with level of antibodies to Chlamydia pneumoniae only in heavily exposed (>or=1000 mGy) survivors. These results may suggest that among atomic bomb survivors, immune response to Chlamydia pneumoniae is diminished and chronic inflammatory reactions related to Chlamydia pneumoniae infection are present.     

Mixed infections with <Emphasis Type="Italic">Chlamydia</Emphasis> and porcine epidemic diarrhea virus - a new <Emphasis Type="Italic">in vitro</Emphasis> model of chlamydial persistence

Background  

Chlamydiae induce persistent infections, which have been associated with a wide range of chronic diseases in humans and animals. Mixed infections with Chlamydia and porcine epidemic diarrhea virus (PEDV) may result in generation of persistent chlamydial infections. To test this hypothesis, an in vitro model of dual infection with cell culture-adapted PEDV and Chlamydia abortus or Chlamydia pecorum in Vero cells was established.     

Association of the −33C/G <Emphasis Type="Italic">OSF</Emphasis>-<Emphasis Type="Italic">2</Emphasis> and the 140A/G <Emphasis Type="Italic">LF</Emphasis> gene polymorphisms with the risk of chronic rhinosinusitis with nasal polyps in a Polish population

Nasal polyps are strongly associated with a risk of chronic rhinosinusitis development as well as other obstruction including asthma and allergy. The following study tested the association of the 140A/G polymorphism of lactoferine (LF) encoding gene and the −33C/G polymorphism of osteoblast-specific factor-2 (OSF-2) encoding gene with a risk of chronic rhinosinusitis with nasal polyps in a Polish population. One hundred ninety five patients of chronic rhinosinusitis with nasal polyps as well as 200 sex, age and ethnicity matched control subjects without chronic sinusitis and nasal polyps were enrolled in this study. Among the group of patients 63 subjects were diagnosed with allergy and 65 subjects with asthma, respectively. DNA was isolated from peripheral blood lymphocytes of patients as well as controls and gene polymorphisms were analyzed by restriction fragments length polymorphism polymerase chain reaction (RFLP-PCR). We reported that the 140A/G LF (OR 4.78; 95% CI 3.07–7.24), the −33C/G OSF-2 OR 3.48; 95% CI 2.19–5.52) and the −33G/G OSF-2 (OR 16.45; 95% CI 6.71–40.30) genotypes were associated with an increased risk of chronic rhinosinusitis with nasal polyps among analyzed group of patients. Moreover, the group of patients without allergy or asthma indicated the association of the −33C/G (OR 3.72; 95% CI 2.24–6.19 and OR 15.11; 95% CI 5.91–38.6) and −33G/G (OR 3.73; 95% CI 2.24–6.19 and OR 14.07; 95% CI 5.47–36.16) genotypes of the OSF-2 as wells as 140A/G (OR 3.89; 95% CI 2.40–6.31 and OR 3.62; 95% CI 2.45–5.34) genotype of OSF-2 with an increased risk of chronic rhinosinusitis with nasal polyps. Finally, it was also found that the selected group of patients with allergy or asthma indicated a very strong association of the −33C/G (OR 2.40; 95% CI 1.23–4.69 and OR 2.40; 95% CI 1.23–4.69, respectively) and −33G/G (OR 16.01; 95% CI 5.77–44.41 and OR 17.90; 95% CI 6.53–49.05, respectively) genotypes of the OSF-2 as wells as 140A/G (OR 3.22; 95% CI 1.74–6.11 and OR 3.25; 95% CI 1.75–6.04, respectively) genotypes with an increased risk of chronic rhinosinusitis with nasal polyps. Thus, our results suggest that LF and OSF-2 gene polymorphisms may have deep impact on the risk of rhinosinusitis nasal polyps’ formation which may also depend on asthma or allergy. Our results showed that the 140A/G polymorphism of LF gene and the −33C/G polymorphism of the OSF-2 gene may be associated with the risk of chronic rhinosinusitis with nasal polyps in a Polish population.     

Resection of obstructing inferior turbinates following rhinoplasty

Total inferior turbinectomy was carried out in 38 patients who complained of nasal obstruction following rhinoplasty or rhinoseptoplasty and in whom hypertrophied inferior turbinates were found to be the cause of obstruction. Postoperatively, relief of nasal obstruction was reported by 84 percent of patients, while rhinoscopy showed wide, clean nasal airways in 92 percent. Nasal airflow measurements in 32 tested patients showed increased patency in all of them, including 3 who still complained of nasal obstruction postoperatively. The follow-up period ranged from 1 to 7 years (mean 2.8 years). Atrophic changes of the nasal mucosa or chronic purulent infection was not observed in any of the patients. Because the results of partial procedures on the inferior turbinates are often unsatisfactory, I suggest performing total inferior turbinectomy in patients with obstructing inferior turbinates following rhinoplasty.     

Mucociliary clearance in chronic sinusitis: related human nasal clearance and in vitro bullfrog palate clearance

Nasal mucociliary clearance was measured in both healthy subjects and patients with chronic sinusitis using saccharin granule technique. Nasal mucociliary transit time (ST) was significantly slower in the patients with chronic sinusitis compared with that in controls (p less than 0.005). Nasal mucus collected from each nasal cavity was used for in vitro bullfrog palate clearance studies and compared to the in vivo nasal ST. Mucociliary clearance rate (MTR) on frog palate was 12.5 +/- 2.5 mm/min in the mucus from control subjects, 6.1 +/- 1.5 mm/min in the mucus from the patients. The difference was statistically significant (p less than 0.005). The MTR on frog palate in the patients whose nasal ST was within normal range was significantly slower than that in controls (p less than 0.005), but not significantly different from that in the patients whose nasal ST was over the normal range. These results suggest that the nasal mucous properties which decreased the mucociliary clearance on frog palate did not contribute to the mucociliary clearance of the patients who had a normal one. No significant correlation existed between MTR on frog palate and nasal ST in both control and chronic sinusitis. In chronic sinusitis patients, decelerated nasal ST was recovered significantly by normal saline nebulization compared with the value before the nebulization (p less than 0.01). None of the significant change of ST was observed in control before and after the nebulization.     

Serological profiling with Chlamycheck, a commercial multiplex recombinant antigen Western blot assay of chlamydial infections

A new chlamydial test system, the Chlamycheck assay, which uses 4 purified recombinant antigens of Chlamydia trachomatis and Chlamydophila pneumoniae and one antigen of Chlamydophila psittaci, has been developed and commercialized. We investigated the reactivities of the recombinant antigens with sera from a group of 30 patients with acute Chlamydia trachomatis infection, 88 patients consulting for sexually transmitted infections, and 46 patients with serological evidence of Chlamydophila pneumoniae infection. The results obtained from human and infected mouse sera suggest that Chlamycheck serology against multiple proteins may provide additional useful information that is not available by conventional whole elementary body microimmunofluorescence or single-antigen enzyme-linked immunosorbent assay serology. Specific serological profiles were associated with acute versus past Chlamydia trachomatis infection or with Chlamydia trachomatis primo-infection versus infection in a Chlamydophila pneumoniae history context.     

Chronic headache: the role of deformity of the nasal septum.

To ascertain a possible causal relation between chronic headache and nasal stenosis arising from deformity of the nasal septum 79 people suffering from both symptoms were observed over one year. On entry to the study they were randomly allocated to either an operative or a control group. The patients in the operative group underwent nasal reconstructive surgery, and the control patients were observed without treatment. Comparison of the two groups showed a considerable decrease in headache after operation. These findings support the suggestion of a causal relation between chronic headache and nasal stenosis and indicate that a nasal origin should be borne in mind in cases of otherwise unexplained chronic headache.     

Analysis of gene expression in penicillin G induced persistence of Chlamydia pneumoniae

Chlamydia pneumoniae is responsible for respiratory tract infections and has been associated to chronic diseases such as atherosclerosis. The involvement of C. pneumoniae in chronic diseases may be correlated to its ability to induce persistent forms in which Chlamydiae remain viable but are not cultivable. The aim of our study is to investigate C. pneumoniae specific gene activities associated with the development of Chlamydial persistence in a cell culture system in the presence of penicillin G. Chlamydia-infected HEp 2 cells were incubated with or without penicillin G for up to 72 hours. The relative mRNA expression levels of early and late genes in treated and untreated cell cultures were determined by Real-time RT-PCR. Our results revealed a consistent down-regulation of Chlamydial hctA and hctB genes (p=0.012 and p=0.003 respectively) in association with up-regulation of htrA gene (p=0.002) during penicillin G-induced persistence suggesting these gene sets as leading candidate for in vivo investigation of the development of persistent Chlamydial infection. In conclusion, the Chlamydial expression pattern of hctA, hctB, and htrA genes may be helpful to identify target molecules to diagnose and treat Chlamydia-associated chronic diseases.     

Microflora of nasal mucosa in patients with maxillar sinusitis

Quantitative and qualitative composition of microflora of nasal mucosa as well as carriage of staphylococci was assessed in patients with chronic and acute forms of maxillary sinusitis. Changes in microflora of nasal mucosa and presence of pathogenic and persistence-associated characteristics of staphylococci in both forms of maxillary sinusitis were revealed. Increase of resistance staphylococci to antibiotics in patients with chronic form of maxillary sinusitis was shown.     

Diffuse peritonitis and chronic ascites due to infection with Chlamydia trachomatis in patients without liver disease: new presentation of the Fitz-Hugh-Curtis syndrome.

Two women were admitted for increasing abdominal pain, vaginal discharge, and severe or moderate chronic ascites. Diffuse peritonitis without evidence of liver disease was found in both cases, and in one the ascites and vaginal discharge contained Chlamydia trachomatis. Both patients responded to doxycycline, and this and the laboratory findings pointed strongly to C trachomatis as the aetiological agent. C trachomatis may cause severe peritoneal infections with chronic ascites formation in the absence of liver disease in women with the Fitz-Hugh-Curtis syndrome. Prompt diagnosis and antibiotics lead to rapid cure.     

A follow-up study of mucociliary clearance and trace element and mineral status in children with chronic rhinosinusitis before and three months after endoscopic sinus surgery

BackgroundThe existing data demonstrate the potential role of trace elements in nasal mucociliary clearance, although the association between trace element and mineral status and ciliary function in children with chronic rhinosinusitis is insufficiently studied. Therefore, the objective of the present study is evaluation of trace element and mineral status and mucociliary function in pediatric CRS patients before and after functional endoscopic sinus surgery.MethodsThe present study involved 30 children with chronic rhinosinusitis without nasal polyps. During this follow-up the patients were examined preoperatively (point 0), underwent functional endoscopic sinus surgery, and were repeatedly examined at three months postoperatively (point 1). At both points the patients were subjected to quality-of-life assessment using SNOT-20 questionnaire; endoscopic and computer tomography examination of the nasal sinuses; evaluation of ciliary function and mucosal cytology using high-speed videomicroscopy; assessment of blood count and inflammatory markers; as well as analysis of trace element and mineral levels in whole blood, serum, and hair using inductively-coupled plasma mass-spectrometry.ResultsThe obtained data demonstrate that endoscopic sinus surgery significantly improved sinonasal pathology in children with chronic rhinosinusitis, as evidenced by significantly reduced Lund-Mackay, Lund-Kennedy, and SNOT-20 scores. At the same time, no significant improvement of ciliary functions or mucosal cytology was observed postoperatively. Trace element status assessment demonstrated that postoperative serum Zn, whole blood Mg and Cu were significantly lower as compared to preoperative values. In contrast, serum Mn and Cr, as well as whole blood Cr and hair Se were characterized by a significant increase at three months postoperatively. Multiple linear regression analysis demonstrated that serum Zn is significantly associated with the number of ciliated cells and cell viability, whereas serum Mn and whole blood Cu concentrations are inversely associated with cell viability and ciliary length, respectively. Hair Se was found to be associated with the number of neutrophils in the mucosa biopsy.ConclusionRedistribution of trace elements and minerals may at least partially mediate prolonged recovery of mucosal ciliary function in children with chronic rhinosinusitis in three months after functional sinus surgery, although the particular mechanisms of these alterations in trace element levels are to be discovered.     

Etiology of chronic prostatitis syndrome in patients treated at the university hospital for infectious diseases "Dr. Fran Mihaljević" from 2003 to 2005

A total of 835 patients with symptoms of chronic prostatitis syndrome and no evidence of structural or functional lower genitourinary tract abnormalities were examined in a three year period at the Outpatient Department for Urogenital Infections, University Hospital for Infectious Diseases "Dr. Fran Mihaljevi?" Zagreb, Croatia. Disease etiology was determined in 482 (57.72%) patients. Chlamydia trachomatis was proved to be the causative pathogen in 161 patients, Trichomonas vaginalis in 85, Escherichia coli in 68, Enterococcus in 51, Proteus mirabilis in 20, Klebsiella pneumoniae in 9, Streptococcus agalactiae in 15, Ureaplasma urealyticum in 49 patients with chronic prostatitis. Other patients had mixed infection. In 257 (53.32%) of 482 patients, the inflammatory finding (>10 WBCs/hpf) was found in EPS or VB3. Normal WBCs/hpf (<10) was found in 103 (63.98%) of 161 patients with symptoms of chronic prostatitis in whom C. trachomatis was detected in EPS or VB3, in 50 (58.82%) of 85 patients in whom Trichomonas vaginalis was isolated, and in 23 (46.94%) of 49 patients in whom Ureaplasma urealyticum was isolated.     

Persistent Chlamydiae and chronic arthritis

Urogenital infection with Chlamydia trachomatis can lead to development of an acute inflammatory arthritis, and this acute disease becomes chronic in some individuals. Research indicates that the organism is present in synovial tissue of patients with chronic disease in a persistent, rather than an actively growing, form. Importantly, metabolic and other characteristics of persistent Chlamydia differ from those of actively growing bacteria. Other studies suggest that Chlamydia pneumoniae can be found in a persistent state in the synovium and that it too may be involved in joint pathogenesis. These and other observations suggest a more complex role for the Chlamydiae in joint disease than previously recognized. This realization should engender a realignment of thinking among clinicians and researchers concerning both mechanisms of chlamydial pathogenesis in the synovium and design of new treatments for the disease.     

Alveolar epithelial cells type II are major target cells for C. pneumoniae in chronic but not in acute respiratory infection

Pulmonary presence of Chlamydia pneumoniae is associated with acute and chronic infections. We show that unapparent chlamydial infection in four out of 31 chronic obstructive pulmonary disease (COPD) patients (12.9%) is characterized by a significant increase in infected alveolar epithelial cells type II (18.2 +/- 3.5% vs. 2.3 +/- 0.9; IHC/ISH) compared to a newly established model of acute chlamydial infection (ACIM) in vital lung specimens from pulmonary lobectomy. Expression of cHSP60 demonstrated pathogen viability and virulence in the ACIM. We conclude that target cells differ in acute and chronic chlamydial infection and suggest the ACIM as a novel tool to analyze the host-pathogen-interactions in acute respiratory infections.     

Keratitis in free-ranging koalas (Phascolarctos cinereus) on Magnetic Island, Townsville.

Seventy free-ranging koalas (Phascolarctos cinereus) from Magnetic Island (Queensland, Australia) underwent an ocular examination, blood collection and serological examination for Chlamydia psittaci antibodies, and an examination of their teeth and genitalia. In 12 koalas long-standing unilateral keratitis was noted and in another 10 animals long-standing bilateral keratitis was observed. All animals were seronegative for Chlamydia psittaci and apart from some nasal discharge and a variety of assorted medical findings there was no sign of chlamydial infection. These ocular findings probably represent a new disease of unknown etiology.     

Nasal surgery complications

This study examines the incidence of serious complications in nasal surgery and discusses the diagnosis and management of these complications. The authors review 259 consecutive cases performed between January 1, 1983, and August 31, 1988. One-hundred and ninety-five patients had septorhinoplasties, 29 had septoplasties, and 35 had rhinoplasties. Thirteen of these cases involved serious complications as follows: hemorrhage (5), perforation (4), infections (3), and pneumocephalus (1). All the patients with these serious complications had associated septal and/or turbinate surgery. The diagnosis and management of these complications will be discussed. In this small series of nasal surgery patients, the incidence of serious complications was 5.0 percent, with no fatalities reported. The higher incidence of serious complications occurred when associated septal and/or turbinate surgery was required. Awareness of these complications is essential because of the increasing number of patients presenting to plastic surgeons for nasal surgery in whom associated septal and/or turbinate surgery is necessary.     

Association of Mucosal Organisms with Patterns of Inflammation in Chronic Rhinosinusitis

Background

Chronic rhinosinusitis is a multifactorial process disease in which bacterial infection or colonization may play an important role in the initiation or persistence of inflammatory response. The association between mucosal bacteria presence and inflammatory patterns has only been partially explored.

Objective

To demonstrate specific mucosal microorganisms possible association with inflammatory patterns.

Methods

We collected nasal polyps or sinus tissues from a clinical selection of six patient groups with defined sinus disease using tissue biomarkers. In the tissues, we detected bacteria using peptide nucleic acid fluorescence in situ hybridization (PNA-FISH).

Results

After reviewing a total of 115 samples (15–20 samples per group), the mucosal presence of Staphylococcus aureus was correlated with IL-5 and SE-IgE positive chronic rhinosinusitis with nasal polyps and nasal polyps from cystic fibrosis patients. Chronic rhinosinusitis without nasal polyps with TNFα >20 pg/ml was associated with the mucosal presence of Pseudomonas aeruginosa.

Conclusion

This study identifies the relationship between intramucosal microbes and inflammatory patterns, suggesting that bacteria may affect the type of inflammation in chronic rhinosinusitis. Additional investigation is needed to further identify the nature of the relationship.     

大面积脑梗塞患者鼻饲一周、二周引起消化道出血的相关因素分析

目的:探讨影响神经内科大面积脑梗塞患者鼻饲后消化道出血的影响因素,以使医护人员采取有效的护理措施预防患者消化道出血,为神经内科防控大面积脑梗塞患者鼻饲后消化道出血提供切实可行的依据。方法:选取2010年9月-2011年9月我院神经内科大面积脑梗塞住院患者400例,分为普通组与对照组,比较两组患者消化道出血的情况。针对消化道出血情况进行调查分析,找出引起大面积脑梗塞患者消化道出血的相关影响因素。结果:数据显示,鼻饲时间长短(一周、二周)与患者发生消化道出血有关联,鼻饲二周患者发生消化道出血机率高于鼻饲一周患者,两组间统计检验,x2=11.329,P<0.05,有显著差异。大面积脑梗塞患者发生消化道出血主要与以下几个因素相关:自身疾病及严重程度、年龄、置管位置、鼻饲技术。结论:护理人员可依据致使患者发生消化道出血的危险因素,有针对性的采取防控措施,降低神经内科患者鼻饲后消化道出血发生率,有效保障患者安全,提高护理质量。     

Nasal nitric oxide levels in cystic fibrosis patients are associated with a neuronal NO synthase (NOS1) gene polymorphism.

Nitric oxide (NO) plays an important role in a number of physiological processes in the airways, including host defense. Although the exact cellular and molecular source of the NO formation in airways is unknown, there is recent evidence that neuronal NO synthase (NOS1) contributes significantly to NO in the lower airways of cystic fibrosis (CF) patients. NOS1 protein has been shown to be expressed in nasal epithelium, suggesting an involvement of NOS1-derived NO in upper airway biology. We here hypothesized that nasal NO concentrations in CF patients are related to genotype variants in the NOS1 gene. Measurements of nasal NO concentration and pulmonary function were performed in 40 clinically stable CF patients. Genomic DNA from all patients was screened for an intronic AAT-repeat polymorphism in the NOS1 gene using polymerase chain reaction and simple sequence length polymorphism (SSLP) analysis. The allele size at that locus was significantly (P = 0.001) associated with upper airway NO. Mean (+/- SD) nasal NO concentrations were 40.5 +/- 5.2 ppb in CF patients (n = 12) with high repeat numbers (i.e., both alleles > or =12 repeats) and 72.6 +/- 7.4 ppb in patients (n = 28) with low repeat numbers (i.e., at least one allele <12 repeats). Furthermore, in the group of CF patients harboring NOS1 genotypes associated with low nasal NO, colonization of airways with P. aeruginosa was significantly more frequent than in patients with NOS1 genotypes associated high nasal NO concentrations (P = 0.0022). We conclude that (1) the variability in CF nasal NO levels are related to naturally occurring variants in the NOS1 gene, and (2) that nasal NOS1-derived NO affects the susceptibility of CF airways to infection with P. aeruginosa.