Increased risk of chronic otitis media in chronic rhinosinusitis patients: a longitudinal follow-up study using a national health screening cohort.

BACKGROUND: Chronic rhinosinusitis (CRS) and chronic otitis media (COM) share pathophysiological mechanisms such as bacterial infection, biofilm, and persistence of the obstruction state of ventilation routes. However, only a few studies have investigated the relationship between these two diseases nationwide and in the general population. The purpose of this study was to determine whether the incidence of COM in patients with CRS differed from that of a matched control from the national health screening cohort. METHODS: Data from the Korean Health Insurance Review and Assessment Service-National Patient Samples were collected from 2002 to 2015. Participants who were treated ≥ ≥ ≥2 times and underwent head and neck computed tomography evaluation were selected. A 1:4 matched CRS group (n=8,057) and a control group (n=32,228) were selected. The control group included participants who were never treated with the ICD-10 code J32 from 2002 to 2015. The CRS group included CRS patients with/without nasal polyps. RESULTS: The incidence of COM was significantly higher in the CRS group than in the control group. In a subgroup analysis, the incidence of COM in all age groups and in men and women was significantly higher in the CRS group than in the control group. More, CRS increased the risk of COM. CONCLUSIONS: A significant association was observed between CRS and COM. This indicates that CRS patients have a high risk of developing COM.

Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron.

OBJECTIVE: Methamphetamine (MA) abuse induces neurotoxicity and causes neuronal cell apoptosis. Gastrodin is a traditional Chinese herbal medicine used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. The present study investigated the neuroprotective effects of gastrodin against MA-induced neurotoxicity in neuronal cells and its potential protective mechanism. METHODS: The primary cortex neuronal culture was divided into four groups (control group, MA group, MA + gastrodin group, and MA + gastrodin + small interfering RNA group). The neurotoxicity of MA was assessed by detecting apoptotic cells by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay and cell viability by cell counting kit 8 (CCK-8) method, the Tuj1-positive cells and the average axonal length were detected by immunofluorescence, and the expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element-binding (CREB), and brain-derived neurotrophic factor (BDNF) proteins were detected by Western blot. RESULTS: The results of CCK-8 assay showed that 0.5 mM MA was an optimal concentration that induced neurotoxicity (p < 0.01). Pretreatment with 25 mg/L gastrodin exerted maximum protective effects on neuronal cells. The expression levels of cAMP, PKA, phosphorylated PKA, CREB, phosphorylated CREB, and BDNF proteins were decreased in the MA group, and pretreatment with gastrodin upregulated the expression levels of these proteins (p < 0.01). The expressions of PKA and CREB proteins showed no significant changes in the control group, MA group, and gastrodin group. Compared the MA + gastrodin + small interfering RNA group with MA + gastrodin group, the Tuj1-positive cells and the average axonal length were decreased significantly, while the number of apoptotic cells was increased (p < 0.05). CONCLUSION: Gastrodin has neuroprotective effects against MA-induced neurotoxicity, which exerts neuroprotective effects via regulation of cAMP/PKA/CREB signaling pathway and upregulates the expression of BDNF.

Risk of malignancy according to sub-classification of the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) category in the Bethesda system for reporting thyroid cytopathology.

OBJECTIVE: According to the Bethesda System for Reporting Thyroid Cytopathology, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is a heterogeneous category that includes cases with architectural and/or nuclear atypia insufficient to warrant classification as malignant neoplasms. The ambiguous and descriptive characteristics of the AUS/FLUS category mean that the impact of the present guidelines on repeat fine needle aspiration (FNA) is unclear. The present study reclassified AUS/FLUS cases into four sub-categories and then correlated them with histological or cytological follow-up data to clarify the risk of malignancy. METHODS: Ninety-four cases of AUS/FLUS with available follow-up data were reviewed and assigned to one of four sub-categories: (i) AUS-N (nuclear atypia); (ii) AUS-A (architectural atypia); (iii) AUS-O (predominant oncocytic changes); and (iv) AUS-N/A (both nuclear and architectural atypia). The four sub-categories were correlated with subsequent histological or cytological follow-up data, including core needle biopsy, resection, or repeat FNA. RESULTS: Malignancy was identified in 34 of 94 cases (36.2%). The upper limit estimate for malignancy was 43.6%, and the lower limit estimate was speculated as 9.8%. The malignancy rate was highest in cases within the AUS-N sub-category (65.8%, range 16.6%-78.1%). CONCLUSIONS: The present study suggests that cases in the AUS/FLUS category have a higher risk of malignancy than previously thought. Because of the heterogeneous nature of the AUS/FLUS category, further sub-classification might be more effective in achieving appropriate risk stratification and better clinical management.

Identifying fibromyalgia subgroups using cluster analysis: Relationships with clinical variables.

BACKGROUND: Patients with fibromyalgia (FM) exhibit significant clinical heterogeneity, in terms of physical, social and psychological functions, as well as therapeutic responses. Here, we examined FM patients in terms of pain, physical, social and psychological variables to identify clinical subgroups that may be predictive of treatment patterns. METHODS: A total of 313 FM patients were interviewed using a structured questionnaire that included sociodemographic data, current or past FM symptoms and current use of relevant medications. A K-means cluster analysis was conducted using variables reflecting tender points, the Fibromyalgia Impact Questionnaire, Beck Depression Inventory, State-Trait Anxiety Inventor and Social Support Scale. RESULTS: Four distinct clusters were identified in these patients. Group 1 was characterized by high pain levels, severe physical and mental impairment and low social support. Group 2 had moderate pain and physical impairment, mild mental impairment and moderate social support. Group 3 had moderate pain, low physical and moderate mental impairment and low social support. Group 4 had low pain levels, nearly normal physical and mental function and high social support. Group 1 was more often a current or past smoker, more likely to have a variety of symptoms, including swelling, cognitive dysfunction, dizziness, syncope, oesophageal dysmotility, dyspepsia, irritable bladder, vulvodynia and restless leg syndrome. CONCLUSIONS: We identified four subgroups of FM patients based on pain, physical, social and psychological function. These subgroups had different clinical symptoms and medication profiles, suggesting that FM may be better managed using a more comprehensive assessment of an individual patient's symptoms. SIGNIFICANCE: FM patients can be clustered into four distinct subgroups based on clinically measurable variables - pain, physical involvement, psychological function and social support. These subgroups had different clinical symptoms and medication profiles.

Prognostic impact of preoperative neutrophil-to-lymphocyte ratio after radical prostatectomy in localized prostate cancer.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in patients with metastatic castration-resistant prostate cancer receiving systemic therapy. However, the prognostic significance of NLR was never previously evaluated in patients who underwent radical prostatectomy (RP) for prostate cancer. In the present study, we investigated the influence of NLR on survival after a RP for prostate cancer. METHODS: We retrospectively reviewed clinical data of 2301 patients with prostate cancer who underwent RP at our institution between 2000 and 2010. Among these patients, we considered only patients who had a preoperative complete blood count with differential result available. Patients who received neoadjuvant or postoperative adjuvant treatment (radiation, androgen deprivation therapy or both) and those without adequate medical record were excluded. A Kaplan-Meier analysis was performed to analyze biochemical recurrence-free survival (BCRFS), overall survival (OS) and prostate cancer-specific survival (CSS). Univariate and multivariate Cox regression models were used for each end point. RESULTS: In total, 2067 patients were evaluated; median follow-up time was 78 months (interquartile range (IQR) 65-96), median age at RP was 66 years (IQR 61-70) and median preoperative NLR was 1.76 (IQR 1.35-2.40). A Kaplan-Meier analysis showed a significant association between high NLR (⩾1.76) and decreased CSS (P=0.005) and OS (P=0.003) but not with BCRFS (P=0.223). In the univariate and multivariate regression analyses, a high NLR was a significant predictor of CSS (hazard ratio (HR) 2.012, 95% confidence interval (CI) 1.222-3.310, P=0.006) and OS (HR 1.650, 95% CI 1.127-2.416, P=0.010). CONCLUSIONS: This study shows that in patients with prostate cancer preoperative NLR is an independent prognostic factor for OS and CSS after a RP and suggests that a preoperative hematologic workup should be considered in the risk assessment of these patients.

Risk factors for recurrence in patients with papillary thyroid carcinoma undergoing modified radical neck dissection.

BACKGROUND: This study evaluated the impact of lymph node-related factors on the risk of and site of recurrence in patients who had papillary thyroid carcinoma with lymph node metastasis in the lateral compartment (classified as pN1b). METHODS: Patients underwent total thyroidectomy with unilateral modified radical neck dissection for classical papillary thyroid carcinoma. Risk factors for recurrence were evaluated according to the pattern of recurrence. RESULTS: A total of 324 patients were included in the study. The median follow-up was 63 (range 14-181) months. Recurrence was detected in 47 patients (14·5 per cent). In the multivariable analysis, a maximum diameter of metastatic lymph nodes larger than 2·0 cm (hazard ratio (HR) 1·15, 95 per cent c.i. 1·06 to 1·25; P = 0·033) and a central compartment metastatic lymph node ratio of more than 0·42 (HR 3·35, 1·65 to 6·79; P < 0·001) were identified as independent risk factors for locoregional recurrence. Age 45 years or older (HR 5·69, 1·24 to 26·12; P = 0·025) and extranodal extension of metastasis (HR 12·71, 1·64 to 98·25; P = 0·015) were risk factors for distant metastasis. In subgroup analysis of locoregional recurrence, several lymph node-related factors affected the risk of recurrence according to the specific site of metastasis. CONCLUSION: Lymph node-related factors are of importance for the risk of recurrence in patients with classical papillary thyroid carcinoma classified as pN1b.

Association between catechol-O-methyl transferase gene polymorphisms and fibromyalgia in a Korean population: A case-control study.

BACKGROUND: Although polymorphisms of the catechol-O-methyl transferase (COMT) gene have been implicated in altered pain sensitivity, results concerning the association between COMT gene polymorphisms and fibromyalgia (FM) are equivocal. We assessed the associations between COMT single-nucleotide polymorphisms (SNP) and FM risk and symptom severity. METHODS: In total, 409 FM patients and 423 controls were enrolled. Alleles and genotypes at five positions [rs6269 (A>G), rs4633 (C>T), rs4818 (C>G), rs4680 (C>G) and rs165599 (A>G)] in the COMT gene were genotyped from peripheral blood DNA. RESULTS: Alleles and genotypes of the rs4818 COMT gene polymorphism were significantly associated with increased susceptibility to FM. The rs4818 GG genotype was more strongly associated with FM compared to the CC genotype (OR = 1.680, 95% CI: 1.057, 2.672, p = 0.027). Although allele and genotype frequencies did not differ among groups, the rs4633 CT genotype was not associated with the presence of FM following adjustment for age and sex (OR = 0.745; 95% CI: 0.558, 0.995; p = 0.046). However, no association was observed between clinical measures and individual COMT SNPs. In haplotype analysis, there was a significant association between ACG haplotype and FM susceptibility sex (OR = 2.960, 95% CI: 1.447, 6.056, p = 0.003) and the number of tender points (p = 0.046). CONCLUSIONS: This large-scale study suggests that polymorphisms of the COMT gene may be associated with FM risk and pain sensitivity in Korean FM patients. However, our results differed to those of previous studies, suggesting ethnic variation in COMT gene polymorphisms in FM. WHAT DOES THIS STUDY ADD: By contrast to Caucasian and Latin-American populations, the COMT gene polymorphisms are associated with FM risk and pain sensitivity in Korean FM patients, suggesting ethnic variation in COMT gene polymorphisms.

Rate and associated factors of solifenacin add-on after tamsulosin monotherapy in men with voiding and storage lower urinary tract symptoms.

AIM: To explore the rate of add-on therapy with solifenacin in men with voiding and storage lower urinary tract symptoms (LUTS) after tamsulosin monotherapy and to explore predictive factors for starting solifenacin add-on therapy. METHODS: Men aged ≥ 45 years with IPSS ≥ 12 and symptoms of OAB (OAB-V8 ≥ 8, micturition ≥ 8/24 h, urgency ≥ 2/24 h) were enrolled to receive tamsulosin 0.2 mg once daily. After 4 weeks, men with residual symptoms of OAB and reported 'dissatisfied' or 'a little satisfied' were received solifenacin 5 mg in combination with tamsulosin monotherapy. Subjects completed an IPSS, a Quality of life (QoL) index, OAB V8, and an International Consultation of Incontinence Questionnaire (ICIQ)-Male LUTS, and patient perception of bladder condition (PPBC) at baseline and week 4. RESULTS: Of a total of 305 patients, 254 patients completed 4 weeks of tamsulosin treatment. For 176 patients, solifenacin was added (69.3%). Significant predictive factors of solifenacin add-on therapy included long LUTS duration, high IPSS, number of micturitions per 24 h, more urgency episodes, high urgency severity score in a voiding diary and high OAB V8 score. Based on multivariable analysis, potential predictive factors of solifenacin add-on therapy included long LUTS duration (OR = 1.008, 95% CI: 1.001-1.014), high serum PSA (OR = 1.543, 95% CI: 1.136-2.095) and small prostate size (OR = 0.970, 95% CI: 0.947-0.994) (p < 0.05). IPSS, daytime micturitions and urgency episodes, OAB V8 scores, ICIQ and PPBC were improved after tamsulosin monotherapy. CONCLUSIONS: Two thirds of men with voiding and storage LUTS needed to add anticholinergics after 4 weeks of tamsulosin monotherapy. Patients with longer lasting symptoms and storage symptoms with small prostate volume may require the anticholinergic add-on.

Short-term changes of intraocular pressure after cervical interlaminar epidural injection: a pilot study.

BACKGROUND: Cervical epidural injection (CEI) is widely performed on patients with intervertebral disc herniation. The aim of the present study was to investigate the short-term effects of CEI on non-invasive intraocular pressure (IOP) measurements in subjects with normal eyes. METHODS: This prospective study enrolled 15 patients who were undergoing CEI at the C5/6 level with an interlaminar approach in the left lateral decubitus position. IOP was measured in both eyes by a rebound tonometer (Icare-PRO, Icare Finland Oy, Helsinki, Finland). A total volume of 14 ml (4 ml non-ionic contrast, a mixture of 0.2% lidocaine 1 ml and normal saline 4 ml for irrigation and a mixture of normal saline 4.5 ml with non-particulate betamethasone 2 mg) was injected with 1.0 ml s(-1). IOP was measured 5 min after the lateral decubitus position (T0, baseline), immediately after CEI (T1), and 1 min intervals for 5 min (T2-T6). RESULTS: The values of left and right baseline IOP (T0) were 18.9 (2.0) and 15.6 (2.6) mm Hg, respectively. IOP of left and right eyes at T1 [26.6 (4.2) and 21.2 (2.5) mm Hg, respectively] and T2 [26.2 (4.5) and 21.0 (2.8) mm Hg, respectively] were significantly higher compared with T0. These values immediately decreased at T3 and returned to baseline levels within 5 min after CEI. CONCLUSIONS: CEI resulted in an elevation of IOP of both eyes. However, the effects were transient only lasting a few minutes.

A rare case of interparietal incisional hernia from 8 mm trocar site after robot-assisted laparoscopic prostatectomy.

Trocar site hernia arising from 8 mm robotic port is very rare despite the increasing prevalence of robot-assisted surgeries. To date, there had been only a single case reported in the literature. We report a case of small bowel obstruction secondary to an interparietal trocar site incisional hernia after robot-assisted laparoscopic prostatectomy. Meticulous closure of 8 mm robotic trocar sites associated with large peritoneal defect at the end of surgery should be performed.

Effectiveness of the Streamlined Liner of the Pharynx Airway (SLIPATM) in allowing positive pressure ventilation during gynaecological laparoscopic surgery.

The aim of this study was to assess whether the Streamlined Liner of the Pharynx Airway (SLIPA) performed as well as an endotracheal tube for positive pressure ventilation in gynaecological laparoscopic surgery in the Trendelenburg position. Forty patients (American Society of Anesthesiologists physical status I to III) were randomly divided into two groups: SLIPA (n = 20) or endotracheal tube group (n = 20). Lung mechanics and severity of postoperative sore throat were assessed in both groups. In the SLIPA group, the oropharyngeal leak pressure was also measured. There were no significant differences between groups in the lung mechanics. In the SLIPA group, oropharyngeal leak pressure and peak inspiratory pressure increased significantly after gas insufflation compared to 10 minutes after patient positioning in the lithotomy position (P < 0.05). The difference between oropharyngeal leak pressure and peak inspiratory pressure (approximately 10 cmH2O throughout the procedure) remained suitable for airway maintenance. The incidence of sore throat was similar in both groups but the severity was less in the SLIPA group 24 hours after surgery (P < 0.05). There were no other complications such as regurgitation noted in either group. In the study population, the SLIPA performed as well as an endotracheal tube in allowing positive pressure ventilation without gas leak during gynaecological laparoscopy. The way in which the SLIPA increases its resistance to gas leak as the inspiratory pressure rises may account for this.

Long-term outcome of tamsulosin for patients with lower urinary tract symptoms according to the treatment response defined by lower urinary tract symptom outcomes score.

UNLABELLED: IMS: To evaluate long-term outcome of tamsuolsin 0.2 mg for benign prostatic hyperplasia (BPH) patients using a new subjective assessment of patient-reported outcomes and the lower urinary tract symptoms (LUTS) outcome score (LOS) over a 48-week period. METHODS: This study investigated the long-term outcomes of either well-responded or poorly responded patient group as defined by LOS at the period of 12 weeks after BPH treatment. Outcome parameters used in this study were the most bothersome symptoms, BPH K1-short form as well as International Prostate Symptom Score (IPSS), maximum flow rate (Qmax) and postvoiding residual urine volume at 24-, 36- and 48-week follow-up. RESULTS: Of the 414 patients recruited initially, 310 (75.2%) were defined as the responders and 39 (9.5%) as the non-responders to the treatment at 12 weeks, which was stratified by LOS. In this long-term study, the differences in improvement rates of clinical parameters between responder and non-responder groups at 12 weeks of treatment were maintained over the period of 48 weeks. Among the responder patients, most (75.6%) chose continuous administrations of tamsulosin. Improvements in clinical parameters were maintained in this subgroup. It is noteworthy that the improvements in clinical parameters of the non-responder group were dismal despite switching to the other treatment modalities. CONCLUSIONS: Long-term tamsulosin 0.2 mg for BPH patients is an effective treatment, both subjectively and objectively. Considering its integrative nature, LOS seemed to be one of the useful tools to predict the outcome after the management of LUTS.

The influence of obesity on postoperative inflammatory cytokine levels.

Obesity is a chronic inflammatory state and adipose tissue serves as a source of inflammatory mediators. This study compared plasma levels of the proinflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in 20 morbidly obese patients (group O) undergoing laparoscopic Roux-en-Y gastric bypass surgery and in 20 non-obese control patients (group C) undergoing laparascopic gastrectomy. Blood was sampled preoperatively and at 3 and 24 h postoperatively. Postoperative IL-6 levels increased significantly in both groups, but were significantly lower in group O than in group C. Age- and anaesthetic timeadjusted IL-6 levels showed a significant increase at 24 h postoperatively compared with preoperative values in both groups; changes were significantly greater in group C. TNF-α levels did not change significantly over time, but were significantly lower in group O at 3 h postoperatively compared with group C. In conclusion, postoperative changes in IL-6 and TNF-α levels in morbidly obese patients were lower than in non-obese patients. Adipose tissue appears not to contribute to the acute postoperative inflammatory response.

Caudal epidural block in children: comparison of needle insertion parallel with caudal canal versus conventional two-step technique.

This study compared the technique of inserting the needle for caudal epidural blockade in a single pass parallel to the caudal canal versus the conventional technique of approaching the caudal canal with the needle at a steeper angle. Seventy-five patients, aged 0 to 72 months, scheduled for urological surgery were prospectively enrolled in this study. Patients were randomly divided into two groups: a conventional method group (caudal block performed with conventional needle insertion, n=40) and a new method group (needle inserted into the skin at an angle of 200 and into the caudal space without redirection, n=35). Two anaesthetists (A, B) performed the caudal blocks. For anaesthetist A, the mean time required (standard deviation) to perform needle insertion in the conventional method group was 2.2 (0.8) minutes and in the new method group 1.1 (0.7) minutes (P = 0.03). For anaesthetist B the mean time (standard deviation) to perform needle insertion in the conventional method group was 2.1 (1.1) minutes and in the new method group 1.3 (0.8) minutes (P = 0.04). Successful block was considered as first pass placement of the needle in the caudal canal confirmed (after placement) by ultrasound imaging, and the absence of a bloody tap. Subcutaneous placement of the needle after the first attempt occurred in two cases in the conventional method group and three cases in the new method group. Bloody tap occurred in four cases, all in the conventional method group and none in the new method group. When required, the second pass was successful in all cases.

Endoscopically assisted reduction of nasal bone fractures.

The standard treatment for a nasal bone fracture is closed reduction within 10 days. After that time, callus and fibrous connective tissue will limit a precise reduction. This study evaluated endoscopically assisted reduction for the treatment of nasal bone fractures in patients who miss the optimal operating time. Fifteen patients underwent endoscopically assisted correction of nasal bone fractures. The surgery was performed with the patients under general anesthesia. An intercartilaginous incision was made. The depressed bony fragments were repositioned under endoscopic visualization. In all cases, good anatomic reduction was obtained, the postoperative course was uneventful, with no complications, and the patients were satisfied with the shape of their noses. Endoscopy appears to be the best tool for visualizing intraoperative repositioning control, enabling the surgeon to confirm a fracture site with callus and to perform an accurate reduction. Endoscopically assisted reduction provides an alternative option in the treatment of patients outside the optimal temporal window for surgery.

Effect of active smoking on asthma symptoms, pulmonary function, and BHR in adolescents.

BACKGROUND: Active smoking is known to increase asthma symptoms and bronchial hyper-responsiveness (BHR) while decreasing pulmonary function in adults, but few studies have addressed these issues in adolescents. METHODS: We conducted a cross-sectional survey involving questionnaires and assessment of urinary cotinine levels among 1,492 adolescents from three urban areas of South Korea. Current smoking was defined as having smoked more than 1 day in the prior 30 days or having urine cotinine levels >or=100 ng/ml. Spirometry, skin tests, and methacholine challenge tests were performed on adolescents in Seoul (n = 724). RESULTS: The prevalence of current smoking was 8.2% in boys and 2.4% in girls. Reports of wheeze and exercise-induced wheeze in the previous 12 months were more frequent in smokers than nonsmokers (15.2% vs. 8.5%, P = 0.024, and 20.4% vs. 10.7%, P = 0.004, respectively). In multiple logistic regression analysis, current smoking was found to be a significant risk factor for having wheezed in previous 12 months (OR = 4.5, 95% CI 1.5-13.2) and having exercise-induced wheezing in previous 12 months (OR = 8.7, 95% CI, 3.7-20.9). The subgroup analysis revealed that the FEV(1)/FVC was lower in smokers than nonsmokers (mean +/- SD, 105.1 +/- 8.6% vs. 107.8 +/- 7.8%, P = 0.019). In contrast, there was no significant difference in BHR. The effect of smoking on asthma symptoms were more pronounced in non-atopic compared with atopic adolescents. CONCLUSION: Current smoking was significantly associated with symptoms of asthma, such as having recent wheezing and recent exercise-induced wheezing, especially for non-atopics, in Korean adolescent population. Current smoking was further associated with lower pulmonary function, but not BHR.

Expression of transgenes in midbrain dopamine neurons using the tyrosine hydroxylase promoter.

Billions of neurons are interconnected in the central nervous system (CNS). Identification of specific neuronal circuit is indispensable for understanding the relationship between structure and function in the CNS. The midbrain dopamine (DA) neuron system consists of the retrorubral area (A8), the substantia nigra (SN; A9) and the ventral tegmental area (VTA; A10). We hypothesized that genetic methods using cell-type-specific promoters may offer the possibility to express tracer molecules in DA neurons to facilitate neuronal tracing. To address this, we used the 2.5 kb rat tyrosine hydroxylase (TH) promoter in adenovirus or adeno-associated virus (AAV) to express tracers specifically in DA neurons. We found that stereotaxic injection of TH promoter containing adenoviral construct resulted in cell-type-specific transgene expression in the noradrenaline (NA) neurons of the locus coeruleus (LC). However, it caused a significant toxicity to DA neurons in the SN. In contrast, stereotaxic injection of TH promoter containing AAV to the SN resulted in cell-type-specific transgene expression in DA neurons with no detectable toxicity. Taken together, our results demonstrate that it is possible to selectively trace DA neuronal circuits in rodent brains using the TH promoter in the context of AAV.

Endovenous laser ablation of the incompetent small saphenous vein with a 980-nm diode laser: our experience with 3 years follow-up.

PURPOSE: To demonstrate the long-term treatment outcomes of endovenous laser ablation (EVA) of incompetent small saphenous veins (SSV) with a 980-nm diode laser. MATERIALS AND METHODS: Eighty-four patients (96 limbs), with varicose veins and reflux in the SSV on duplex ultrasound examination, were treated with a 980-nm diode laser under ultrasound- or fluoroscopy-guidance. Patients were evaluated at 1 week and 1, 3, 6 months, 1 year and yearly thereafter. RESULTS: In the 96 limbs, the technical success rate was 100%. The SSV remained closed in 89 of 93 limbs (96%) after 1 month, all of 82 limbs after 6 months, 77 limbs after 1 year, 71 limbs after 2 years and 55 limbs after 3 years. In four limbs where recanalisation was observed, repeat EVA was done resulting in successful obliteration of the SSV. No major complication occurred however bruising (27%), tightness or pain (13%) and paraesthesia (4.2%) were observed. CONCLUSION: Endovenous laser ablation with a 980-nm laser wavelength is an easy and safe procedure in incompetent SSVs. After successful treatment, there is a very low rate of recanalisation of the SSV, which suggests that the procedure will provide lasting results.

Combined effect of tumour necrosis factor-alpha and interleukin-13 polymorphisms on bronchial hyperresponsiveness in Korean children with asthma.

BACKGROUND: TNF-alpha and IL-13, two pivotal pro-inflammatory cytokines, are increased in asthmatic airways and may be linked to asthma susceptibility and/or bronchial hyperresponsiveness (BHR). OBJECTIVE: We investigated the association between the TNF-alpha-308G/A polymorphism and asthma susceptibility or asthma-related phenotypes in Korean children with asthma, and tested for a combined effect with IL-13 polymorphisms. METHODS: Asthmatic children (n=719) and non-atopic healthy control children (n=243) were evaluated for asthma phenotypes including total serum IgE and BHR to methacholine. Genotypes were determined by PCR-restriction fragment length polymorphism analysis. RESULTS: The allele frequency of TNF-alpha-308A in asthmatics (14.1%) was higher than that in control children [8.7%, odds ratio (OR) 1.72, 95% confidence interval (CI) 1.05-2.82]. Significantly lower PC(20) values were found in asthmatic children carrying one or two copies of the TNF-alpha risk allele (-308A) vs. those homozygous for the common allele (P=0.026). Combined analysis revealed that atopic asthmatic children co-inherited the risk alleles of TNF-alpha-308G/A and IL-13 +2044G/A more frequently than control children (aOR 1.91, 95% CI 1.00-3.65), and asthmatic children co-inheriting both risk alleles had significantly lower PC(20) values vs. asthmatic children homozygous for the common alleles (P=0.024). CONCLUSION: The TNF-alpha promoter polymorphism (-308G/A) may be associated with asthma susceptibility and BHR in Korean children with asthma. In addition, there appears to be a synergistic effect between the TNF-alpha promoter polymorphism and an IL-13 coding region polymorphism in terms of asthma susceptibility and BHR in this population.

Inhibition of VEGF blocks TGF-beta1 production through a PI3K/Akt signalling pathway.

Vascular endothelial growth factor (VEGF) is a mediator of airway inflammation and remodelling in asthma. Transforming growth factor (TGF)-beta(1) plays pivotal roles in diverse biological processes, including tissue remodelling and repair in a number of chronic lung diseases. However, there are few studies elucidating the interactions between VEGF and TGF-beta(1) in allergic airway disease. A murine model of allergic airway disease was used to define the mechanism by which VEGF induces subepithelial fibrosis and to investigate a potential relationship between VEGF and TGF-beta(1) and the mechanisms by which VEGF signalling regulates TGF-beta(1) expression in allergic airway disease. The ovalbumin (OVA)-inhaled murine model revealed the following typical pathophysiological features of allergic airway disease in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased peribronchial fibrosis, and increased levels of VEGF and TGF-beta(1). Administration of VEGF inhibitors reduced the pathophysiological signs of allergic airway disease and decreased the increased TGF-beta(1) levels and peribronchial fibrosis, including phosphoinositide 3-kinase (PI3K) activity after OVA inhalation. In addition, the increased TGF-beta(1) levels and collagen deposition after OVA inhalation were decreased by administration of PI3K inhibitors. These results suggest that inhibition of vascular endothelial growth factor attenuates peribronchial fibrosis, at least when mediated by regulation of transforming growth factor-beta(1) expression through phosphoinositide 3-kinase/Akt pathway in a murine model of allergic airway disease.