Pathological spontaneous activity as a prognostic marker in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: Monitoring of the disease course of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) remains challenging because nerve conduction studies do not adequately correlate with functional disability. The prognostic value of pathological spontaneous activity (PSA) in needle electromyography (EMG) in different CIDP subgroups in a longitudinal context has, to date, not been analysed. We aimed to determine whether PSA was a prognostic marker or a marker of disease activity in a cohort of patients with CIDP. METHODS: A total of 127 patients with CIDP spectrum disorder were retrospectively analysed over 57 ± 47 months regarding the occurrence of PSA (fibrillations and positive sharp waves). The presence of PSA at diagnosis, newly occurring PSA, and continuously present PSA were longitudinally correlated with clinical disability using the Inflammatory Neuropathy Cause and Treatment Overall Disability Sum Score (INCAT-ODSS) and CIDP subtype. RESULTS: Pathological spontaneous activity occurred in 49.6% of all CIDP patients at first diagnosis. More frequent evidence of PSA was significantly associated with a higher INCAT-ODSS at the last follow-up. Continuous and new occurrence of PSA were associated with higher degree of disability at the last follow-up. The majority of patients with sustained evidence of PSA were characterized by an atypical phenotype, higher degree of disability, and the need for escalation of treatment. CONCLUSIONS: Pathological spontaneous activity was associated with a higher degree of disability and occurred more frequently in atypical CIDP variants according to the longitudinal data of a large cohort of patients with CIDP. Our results showed that EMG examination was an adequate marker for disease progression and should be evaluated during the disease course.

Prevalence of sleep disturbance in chronic pain.

OBJECTIVE: Sleep is a vital function for human beings, which can be affected by several factors. Chronic pain is one of these factors where it is the most frequent cause for seeking medical care in combination with insomnia. The aim of this study is to examine the prevalence and relationship between sleep disturbance and chronic pain. PATIENTS AND METHODS: After approval, a total of 85 Family Medicine Units from over 170 in Tokat were randomly selected using a 50% sampling. A sample of 2635 subjects, over the age of 19 years, who were registered with the selected Family Medicine Units, were assessed due to gender, age group, and the urban/rural population size of Tokat using the stratified sampling method. The sample size distribution was calculated as 1515 urban subjects, 1120 rural subjects; 1345 female subjects, 1290 male subjects; 1123 subjects between 20-39 years of age, 1103 subjects between the ages of 40-64, and 409 subjects over 64 years of age. After sampling, subjects were invited to participate in the study via an invitation letter, and agreeing individuals were taken to the Family Medicine Unit for face-to-face meetings. Written, informed consent was obtained, along with demographic data. The presence of chronic pain was recorded. According to the presence of chronic pain, all subjects were separated into two groups as Group Chronic Pain and Group Non-Chronic Pain. The visual analog scale for pain intensity, and Pittsburgh Sleep Quality Index for sleep quality, were performed with all subjects. A multiple linear regression model was used to assess the predictors of sleep quality. Analyses were conducted using the Statistical Package for Social Sciences program (SPSS Inc., Chicago, IL, USA), version 20.0. The statistical significance for all analyses was set at p < 0.05. RESULTS: The mean global Pittsburgh Sleep Quality Index score of Group Chronic Pain (5.30 ± 4.29) was significantly higher than in Group Non-Chronic Pain (3.22 ± 3.30; p < 0.01). The mean Pittsburgh Sleep Quality Index scores of females (5.69 ± 4.40) were significantly higher than males (4.54 ± 3.96) in Group Chronic Pain (p = 0.000045). A total of 40.7% of patients in Group Chronic Pain, and 21.9% in Group Non-Chronic Pain demonstrated poorer sleep quality according to the Pittsburgh Sleep Quality Index scores, with a cut-off level > 5. A moderate positive correlation was found between the global Pittsburgh Sleep Quality Index and Visual Analog Scale scores (r = 0.310, p < 0.01). A multiple linear regression analysis showed that age, gender, income, Visual Analog Scale, and presence of depression were the significant predictors for Pittsburgh Sleep Quality Index score. CONCLUSIONS: The current study revealed that chronic pain and pain intensity are important predictors of sleep quality.

Comparison of manual mycobacteria growth indicator tube and epsilometer test with agar proportion method for susceptibility testing of Mycobacterium tuberculosis.

BACKGROUND AND OBJECTIVES: Antimycobacterial susceptibility tests take weeks, and delayed therapy can lead to spread of Mycobacterium tuberculosis. Therefore, rapid, accurate and cost-effective methods are required for proper therapy selection. In this study, the Mycobacteria growth indicator tube (MGIT) and epsilometer test (Etest) methods were compared to the agar proportion method for susceptibility testing of Mycobacterium tuberculosis. MATERIALS AND METHODS: The susceptibility tests against isoniazid (INH), rifampin (RIF), streptomycin (STM) and ethambutol (ETM) of 51 M. tuberculosis complex isolates were analyzed by the MGIT, Etest and agar proportion methods. RESULTS: The concordance between MGIT/Etest and agar proportion methods was 98% for INH and 100% for RIF, STM, ETM. There were not statistically significant differences in results of the susceptibility tests between MGIT/Etest and the reference agar proportion method. CONCLUSION: The results have shown that MGIT and Etest methods can be used instead of the agar proportion method, because these two methods are more rapid and easier than the agar proportion method.

Prevalence of hepatitis delta virus (HDV) infection in chronic hepatitis B patients in eastern Turkey: still a serious problem to consider.

Hepatitis delta virus (HDV) is a serious cause of liver-related morbidity and mortality. Coexistent infection with HDV tends to aggravate the course of hepatitis B virus (HBV)-associated liver disease. The aim of this study was to determine the prevalence of HDV infection among patients chronically infected with HBV in the Elazig region, which is in eastern Turkey. A group of 282 patients infected with chronic HBV were investigated for the study. Anti-HDV seropositivity was evaluated in all patients. The anti-HDV-positive patients were further tested for HDV RNA. Severity of liver disease was assessed by liver biopsy. Regression analysis was used to determine the relationship between independent variables and HDV positivity. Of 282 chronic HBV patients, 192 were men (68.1%) and 90 were women (31.9%). The mean age was 43.8 ± 12.7 (between 18 and 73 years). Anti-HDV was positive in 45.5% of the patients (128/282). Among the 128 anti-HDV-positive patients, 116 were checked for HDV RNA and 56.9% were found positive (66/116). Chronic HDV infection rate was therefore present in at least 23.4% of the whole study group (66/282). There were 83 patients with cirrhosis (29.4%) in the study group. Anti-HDV seroprevalence and HDV RNA presence were higher in those with cirrhosis (61.4% and 42.2%, respectively). No significant relationship was found between anti-HDV seropositivity and demographic factors such as age, sex and operation or transfusion history except family history. HDV-RNA-positive patients had significantly higher ALT and lower albumin levels when compared to HDV-RNA-negative patients. HDV-RNA-positive patients also had a significantly higher fibrosis stage. In conclusion, these findings demonstrated that HDV infection is endemic and still a serious problem in the Elazig region of eastern Turkey. HDV infection is significantly related to the family exposure and increases the risk of severe liver fibrosis in this region.

In vitro activities of fluconazole, itraconazole and voriconazole against otomycotic fungal pathogens.

OBJECTIVE: To determine the causative pathogens of otomycosis, and to evaluate the in vitro activity of antifungal agents against these pathogens. MATERIALS AND METHODS: A total of 96 fungal isolate were taken from 92 patients suspected of otomycosis. The in vitro activity of fluconazole, itraconazole and voriconazole against otomycotic pathogens was tested using the E-test method. RESULTS: The most common pathogen was Aspergillus fumigatus (40.6 per cent), followed by A niger (35.4 per cent), A flavus (12.5 per cent) and Candida albicans (11.5 per cent). All Aspergillus species were found to be resistant to fluconazole (minimum inhibitory concentration > or =256 microg/ml). The mean minimum inhibitory concentrations of voriconazole for A fumigatus, A niger, A flavus and C albicans were significantly lower than those of itraconazole for the same pathogens. CONCLUSION: This study found that the most common otomycotic fungal pathogen was A fumigatus, and that voriconazole had more potent in vitro activity than itraconazole against all Aspergillus species as well as against C albicans.

Renal involvement as a rare complication of Dorfman-Chanarin syndrome: a case report.

Dorfman-Chanarin syndrome is a rare, autosomal recessive inherited lipid storage disease with congenital ichthyotic erythroderma due to an acylglycerol recycling defect. It is characterized by accumulation of neutral lipids in different tissues. Liver, muscle, ear, eye, and central nervous system are generally involved, so we presented a patient with severe ichthyosis, lipid vacuoles in neutrophils, and multiorgan involvement including a very rare complication, renal involvement. A 7-month-old girl was presented with frequent respiratory infection, congenital ichthyotic erithroderma and suspicion for immune deficiency. On her physical examination hepatomegaly, developmental delay, palmar and plantar hyperkeratosis and increased deep tendon reflexes with clonus and high tonus were found. Laboratory investigations revealed elevation at transaminases levels, hypoalbuminemia, hypergammaglobulinemia, presence of autoantibodies and eosinophilia. Vacuolization in leukocytes confirmed Dorfman-Chanarin syndrome, whereas no mutation at RAG1-2 and ARTEMIS genes ruled-out immune deficient status of the patient. At the age of eight months the patient died from severe renal failure. Her necropsies demonstrated microvesicular lipid accumulation not only at the liver but also at the renal species. The variability of involvement of different systems in Dorfman-Chanarin syndrome is well described, however the renal findings has not been reported previously at the literature.

Serum leptin levels in patients with nasal polyposis.

BACKGROUND: Nasal polyposis is one of the most common inflammatory pathologies of the nasal cavity. The aetiopathogenetic mechanisms of nasal polyp formation are still unclear. OBJECTIVES: The aim of this study was to investigate the serum leptin levels in patients with nasal polyposis. DESIGN: A randomised, prospective study was performed of 28 adult patients with nasal polyposis and 22 control subjects of a similar age, sex and body mass index. RESULTS: Serum leptin levels were 12.10 +/- 9.39 ng/ml in the nasal polyposis patients and 6.17 +/- 7.68 ng/ml in the controls. A significant difference (p = 0.021) was observed in the mean serum leptin levels between nasal polyposis patients and controls. CONCLUSION: Serum leptin levels were found to be significantly higher in patients with nasal polyposis. Leptin, apart from its primary role in the regulation of body weight and energy expenditure, may have a role in the inflammatory response of nasal polyposis.

Seroprevalence of Helicobacter pylori infection in patients with chronic nonspecific pharyngitis: preliminary study.

BACKGROUND AND OBJECTIVES: Chronic nonspecific pharyngitis is a chronic inflammation of the pharynx. It is found worldwide, and treatment is difficult. The underlying aetiopathogenesis is still controversial. The aim of this study was to investigate Helicobacter pylori seroprevalence in chronic nonspecific pharyngitis patients without other possible causative factors for chronic pharyngeal irritation and without H. pylori gastric mucosal infection. MATERIALS AND METHODS: Forty-one patients with symptoms of chronic nonspecific pharyngitis and 30 healthy control subjects were enrolled in this prospective, controlled, clinical study. In both study and control groups, selected patients were shown to have gastric mucosa uninfected by H. pylori, as demonstrated by the 14C-urea breath test. Comprehensive otorhinolaryngological examination did not elicit any factor contributing to the chronic pharyngeal complaint. Serum H. pylori immunoglobulin G antibody titres were assayed using serum enzyme-linked immunosorbent assay. The difference between the study and control groups was analysed by the chi-square test (the likelihood ratio was used). RESULTS: Thirty-two of the 41 patients (78 per cent) and 14 of the 30 control subjects (46.7 per cent) were found to be H. pylori positive. Patients with chronic nonspecific pharyngitis were found to have a significantly higher rate of H. pylori seropositivity than the control group (p = 0.016). CONCLUSION: These data may be important in developing future treatment strategies for chronic nonspecific pharyngitis.

Detection of bacterial translocation during intestinal distension in rats using the polymerase chain reaction.

To investigate whether distension causes bacterial translocation (BT), a rat model reported earlier by us was used and to detect the presence of bacterial DNA in blood by polymerase chain reaction (PCR) assay, the most sensitive detection method to date. In 4 groups of 4-week-old Wistar-albino rats a total of 15 animals each were included. In the 1st group (distension+gavage), 1010 Escherichia coli colonies were given via gavage and distension was carried out by rectal air inoculation. In the 2nd group (gavage), animals were inoculated with E. coli and no distension was induced. The 3rd group (distension) were only distended and no bacteria were inoculated. The control group were neither distended nor inoculated with E. coli. Blood samples were collected 3 h after manipulations and both blood cultures and PCR assays were performed. According to the PCR results BT was evident in 80% of group 1, 20% of group 2, and 33% of group 3 animals. BT was not determined in the control group. Significantly low percentages of positivity were observed in blood cultures in all groups (P < 0.05). These results confirm reports that BT occurs in the presence of distension and that PCR is a superior way of determining BT. Thus, it would be advisable to utilize PCR technology in cases where the possibility of distension exists, as early intervention might be useful before any severe clinical pathology (sepsis, multiple-organ-system failure) becomes evident.

Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling.

Toll-like receptor 2 (TLR2) and TLR4 play important roles in innate immune responses to various microbial agents. We have previously shown that human dermal endothelial cells (HMEC) express TLR4, but very little TLR2, and respond to LPS, but not to Mycobacterium tuberculosis 19-kDa lipoprotein, unless transfected with TLR2. Here we report that HMEC are unresponsive to several additional biologically relevant TLR2 ligands, including, phenol-soluble modulin (PSM), a complex of three small secreted polypeptides from the skin commensal Staphylococcus epidermidis, soluble tuberculosis factor (STF), and Borrelia burgdorferi outer surface protein A lipoprotein (OspA-L). Expression of TLR2 renders HMEC responsive to all these ligands. We further characterized the signaling pathway in response to STF, OspA-L, and PSM in TLR2-transfected HMEC. The TLR2 signaling pathway for NF-kappaB trans-activation shares the IL-1R signaling molecules. Dominant negative constructs of TLR2 or TLR6 inhibit the responses of STF and OspA-L as well as PSM in TLR2-transfected HMEC, supporting the concept of functional cooperation between TLR2 and TLR6 for all these TLR2 ligands. Moreover, we show that Toll-interacting protein (Tollip) coimmunoprecipitates with TLR2 and TLR4 using HEK 293 cells, and overexpression of Tollip inhibits NF-kappaB activation in response to TLR2 and TLR4 signaling. Collectively, these findings suggest that there is functional interaction between TLR2 and TLR6 in the cellular response to STF and OspA-L in addition to S. epidermidis (PSM) Ags, and that engagement of TLR2 triggers a signaling cascade, which shares the IL-1R signaling molecules, similar to the TLR4-LPS signaling cascade. Our data also suggest that Tollip may be an important constituent of both the TLR2 and TLR4 signaling pathways.

Bacteriological and PCR analysis of clinical material aspirated from otitis media with effusions.

Otitis media with effusions (OME) can lead to significant hearing loss in childhood. Although previous studies have shown that bacterial DNA is present in a significant percentage of effusions sterile by culture, whether the DNA represents viable organisms or 'fossilized remains' is unknown. The aim of the present study was the determination of Streptococcus pneumonia, Moraxella catarrhalis and Haemophilus influenza in the clinical materials from OME. For this purpose, effusion samples aspirated from the mid-ear were analyzed bacteriologically. Samples were also tested with polymerase chain reaction (PCR) assay. A total of 37 samples obtained from 20 patients aging between 4 and 14 were analyzed. In 17 patients, both ears demonstrated effusions, whereas in three patients, only one ear had effusions. In aerobic bacterial culture assays, nine samples (24.3%) showed bacterial growth. None of the samples were positive for anaerobic culture experiments. PCR analysis of the samples showed that 35 samples (94.5%) contained bacterial DNA. In 19 samples, only one bacterial species and in 16 samples more than one bacterial species were detected. The results of this study demonstrate that effusion fluid from otitis media cases contain a battery of bacterial species and these bacteria might play roles in the pathogens of OME. Our results indicate the PCR technique is more specific and sensitive in detection of bacteria in middle-ear effusion of OME, compared with conventional methods.

Bacterial lipopolysaccharide activates HIV long terminal repeat through Toll-like receptor 4.

In HIV-infected patients, concurrent infections with bacteria and viruses are known to induce HIV replication as assessed by increases in plasma HIV RNA levels. In the present study, we determined the cell surface receptor and molecular mechanisms of enterobacterial LPS-induced HIV transcription. Human dermal microvessel endothelial cells (HMEC) were transfected with an HIV-long terminal repeat (LTR)-luciferase construct and subsequently stimulated with purified bacterial LPS. Our studies demonstrate that human Toll-like receptor 4 (TLR4) mediates LPS-induced NF-kappaB and HIV-LTR activation in HMEC through IL-1 signaling molecules, namely myeloid differentiation protein, IL-1R-associated kinase, TNFR-associated factor, and NF-kappaB-inducing kinase. Cotransfection of HMEC with HIV-LTR-luciferase and TLR4 cDNA from LPS-hyporesponsive C3H/HeJ mice abrogates LPS-induced HIV transcription as does the use of dominant-negative mutants of the IL-1 signaling molecules. Transfection of HMEC with an HIV-LTR-mutant that lacks the NF-kappaB binding site or pretreatment of cells with chemical inhibitors of the NF-kappaB pathway also blocked LPS-induced HIV-LTR transactivation. These data support the conclusion that TLR4 mediates enterobacterial LPS-induced HIV transcription via IL-1 signaling molecules and NF-kappaB activation plays an important role in HIV-LTR transactivation.

Cholinesterase activity is similar in C3H/HeJ and A/J mice and does not account for their different bronchoconstrictor responsiveness.

Significant interstrain variation in airway responsiveness to acetylcholine (ACh) exists in inbred mouse strains. We hypothesized that part of the variation may be due to between-strain differences in cholinesterase activity. We asked if administration of neostigmine (an acetylcholinesterase inhibitor) and/or succinylcholine (an agent which competes for and inhibits butyrylcholinesterase) altered ACh responsiveness in hyporesponsive C3H/HeJ and hyperresponsive A/J mouse strains. Airway responses to ACh were measured by the airway pressure time index in the presence and absence of succinylcholine (10 mg/kg) and/or neostigmine (0.7 mg/kg). In addition, acetylcholinesterase and butyrylcholinesterase activity were directly measured. Acetylcholinesterase and butyrylcholinesterase inhibition increased airway responses to acetylcholine in both strains, but did not eliminate or decrease the differences in airway responsiveness to ACh previously seen in the two strains. Cholinesterase activities in the two strains were not significantly different. We conclude that differences in either acetylcholinesterase or butyrylcholinesterase in the A/J or C3H/HeJ mouse strains are unlikely to contribute to the differences in airway responsiveness to exogenously administered cholinergic agonists.

Effect of lung inflation in vivo on airways with smooth muscle tone or edema.

Fibrous attachments to the airway wall and a subpleural surrounding pressure can create an external load against which airway smooth muscle must contract. A decrease in this load has been proposed as a possible cause of increased airway narrowing in asthmatic individuals. To study the interaction between the airways and the surrounding lung parenchyma, we investigated the effect of lung inflation on relaxed airways, airways contracted with methacholine, and airways made edematous by infusion of bradykinin into the bronchial artery. Measurements were made in anesthetized sheep by using high-resolution computed tomography to visualize changes in individual airways. During methacholine infusion, airway area was decreased but increased minimally with increases in transpulmonary pressure. Bradykinin infusion caused a 50% increase in airway wall area and an small decrease in airway luminal area. In contrast to airways contracted with methacholine, the luminal area after bradykinin increased substantially with increases in transpulmonary pressure, reaching 99% of the relaxed area at total lung capacity. Thus airway edema by itself did not prevent full distension of the airway at lung volumes approaching total lung capacity. Therefore, we speculate that if a deep inspiration fails to relieve airway narrowing in vivo, this must be a manifestation of airway smooth muscle contraction and not airway wall edema.

Prevention of lidocaine aerosol-induced bronchoconstriction with intravenous lidocaine.

BACKGROUND: Lidocaine applied topically provokes bronchoconstriction in persons with hyperreactive airway disease. The authors questioned whether intravenous lidocaine would prevent lidocaine-aerosol induced bronchoconstriction. They compared the effects of lidocaine administered intravenously and by the aerosol route on baseline airway tone, and on the prevention of histamine-induced bronchoconstriction in five Basenji-Greyhound dogs. METHODS: Dogs were pretreated with either intravenous or aerosol lidocaine followed by histamine aerosol challenge. On separate days, dogs were pretreated with intravenous lidocaine, followed by aerosol lidocaine administration at similar doses. Airway caliber was assessed using high-resolution computed tomography. Data were analyzed by two-way analysis of variance. Serum lidocaine concentrations were obtained. RESULTS: Histamine alone decreased the airway area by 32 +/- 3%. Lidocaine administered intravenously or by the aerosol route significantly inhibited histamine-induced bronchoconstriction. There was no significant difference between the two routes in preventing histamine-induced bronchoconstriction. At the dose that inhibited histamine-induced bronchoconstriction, lidocaine administered by the aerosol route decreased baseline airway area by 27 +/- 3% (P < 0.01), whereas intravenous lidocaine had no effect. Intravenous lidocaine prevented lidocaine aerosol-induced bronchoconstriction, and the combination of intravenous and aerosol lidocaine significantly dilated the airways by 20 +/- 5% (P < 0.01 compared with control). CONCLUSIONS: An intravenous bolus of lidocaine prevents the initial bronchoconstriction induced by lidocaine when administered as an aerosol.