The effect of trapidil and bevacizumab on tracheal anastomotic wound healing.

BACKGROUND: Although bevacizumab has deleterious effects on the healing of colonic anastomoses, trapidil improves wound healing of colonic and tracheal anastomoses. OBJECTIVE: We aimed to assess the effects of bevacizumab and trapidil on wound healing after tracheal transection. MATERIALS AND METHODS: We evaluated 35 rats divided in 5 groups: bevacizumab (Group I, n = 7), trapidil (Group II, n = 7), trapidil + bevacizumab (Group III, n = 7), controls (Group IV, n = 7), and sham (Group V, n = 7). Anastomotic healing was assessed by measurement of bursting pressure and inflammation score at the anastomotic region on the seventh day. RESULTS: The bursting pressures of Group II, Group III, and Group V were significantly higher than controls (P = 0.001, P = 0.033, and P = 0.035, respectively). Fibrosis was significantly high in the sham group when compared with the other four groups (P = 0.047). CONCLUSIONS: Although bevacizumab seems to impair anastomotic healing, trapidil can be suggested to improve tracheal anastomoses.

[Reliability and validity of Turkish version of COPD assessment test]. / KOAH degerlendirme testinin Türkçe geçerlilik ve güvenilirligi.

INTRODUCTION: This study is aimed to evaluate the reliability and validity of the Turkish version of chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) in seven centers. MATERIALS AND METHODS: 321 patients between 4-75 years of age, diagnosed and staged by Global Initiative for Obstructive Lung Disease (GOLD) 2011 criteria were included. The Breathlessness, Cough, Sputum scale (BCSS), mMRC (Modified Medical Research Council ) dyspnea index, St. George Respiratory Questionnaire (SGRQ), CAT and Short Form-36 (SF-36) were used concurrently. In the statistical analyses, internal consistency, item-total score correlation, explorative factor analysis, correlation with other scales were calculated. RESULTS: The mean age was 62.4 ± 8.9 years and 89.7% of the patients were male (n= 288). Mean FEV1% was 51.9 ± 19.2 and most of the patients were in Stage 3. CAT total score was 17.8 ± 9.5. In the internal consistency, Cronbach alpha coefficient was found as 0.9116 and item-total score correlation coefficients were between 0.62-0.79 and all were statistically significant (p< 0.0001). The correlation of the test-retest score calculated after two weeks with the initial score was 0.96 (p< 0.0001). In the structural validity, factor analysis with principle component analysis and varimax rotation was performed. One factor solution was achieved with eigenvalue of 4.956 and it represented 61.9% of the total variance. All the items were contained in the factor and the factor loads were between 0.71-0.85. The correlation coefficients of CAT with other indexes were moderate to good. The discrimination of CAT among disease stages has been shown to be significant (p< 0.0001) and a significant correlation was found with pulmonary function tests (p< 0.0001). CONCLUSION: It is demonstrated The Turkish version of COPD Assessment Tool is reliable and valid.

[How exactly can we predict the prognosis of COPD]. / KOAH hastalarinin progresyonlarini ne ölçüde tahmin edebiliriz?

Predictive models play a pivotal role in the provision of accurate and useful probabilistic assessments of clinical outcomes in chronic diseases. This study was aimed to develop a dedicated prognostic index for quantifying progression risk in chronic obstructive pulmonary disease (COPD). Data were collected prospectively from 75 COPD patients during a three years period. A predictive model of progression risk of COPD was developed using Bayesian logistic regression analysis by Markov chain Monte Carlo method. One-year cycles were used for the disease progression in this model. Primary end points for progression were impairment in basal dyspne index (BDI) score, FEV(1) decline, and exacerbation frequency in last three years. Time-varying covariates age, smoking, body mass index (BMI), severity of disease according to GOLD, PaO2, PaCO(2), IC, RV/TLC, DLCO were used under the study. The mean age was 57.1 + or - 8.1. BDI were strongly correlated with exacerbation frequency (p= 0.001) but not with FEV(1) decline. BMI was found to be a predictor factor for impairment in BDI (p= 0.03). The following independent risk factors were significant to predict exacerbation frequency: GOLD staging (OR for GOLD I vs. II and III = 2.3 and 4.0), hypoxemia (OR for mild vs moderate and severe = 2.1 and 5.1) and hyperinflation (OR= 1.6). PaO2 (p= 0.026), IC (p= 0.02) and RV/TLC (p= 0.03) were found to be predictive factors for FEV(1) decline. The model estimated BDI, lung function and exacerbation frequency at the last time point by testing initial data of three years with 95% reliability (p< 0.001). Accordingly, this model was evaluated as confident of 95% for assessing the future status of COPD patients. Using Bayesian predictive models, it was possible to develop a risk-stratification index that accurately predicted progression of COPD. This model can provide decision-making about future in COPD patients with high reliability looking clinical data of beginning.

Bronchoscopy is associated with decreased mesenteric arterial flow.

BACKGROUND: We hypothesized that fiberoptic bronchoscopy can contribute to mesenteric ischemia and bacterial translocation. OBJECTIVE: To test this hypothesis we investigated in patients undergoing bronchoscopy mesenteric blood flow and markers in association with ischemia reperfusion injury. PATIENT: Forty-seven consecutive patients requiring diagnostic fiberoptic bronchoscopy were studied. MEASUREMENTS: Parameters evaluated were superior mesenteric artery Doppler sonography, oxidative stress mediators, arterial blood gases, blood cultures pre-fiberoptic bronchoscopy, and 1st, 4th, and 24th hr post-fiberoptic bronchoscopy. MAIN RESULTS: After bronchoscopy; PaO2 decreased by 21.8% +/- 1.5% (range 6-40), and remained low at all time points (p = 0.0001, p = 0.0001, p = 0.008). Flow volume decreased by 38.8% +/- 14.9% (range 6-72), and remained low at 1st and 4th hr (p = 0.0001, p = 0.01). Resistive and pulsatile index increased at 1st hr (p = 0.0001, p = 0.001) and 4th hr (p = 0.018, p = 0.045). Myeloperoxidase and malondialdehyde increased at 1st hr (p = 0.0001) and 4th hr (p = 0.037, p = 0.028). Corresponding glutathione and catalase decreased at 1st hr (p = 0.0001), and glutathione remained significant at 4th and 24th hr (p = 0.0001, p = 0.003). Correlation between flow volume and PaO2 (r = .71, p = 0.0001), myeloperoxidase (r = -.39, p = 0.05), glutathione (r = .41, p = 0.03) was significant. Nine of 47 (19.1%) had fever, and 3 of 47 (6.4%) had gram-negative bacteremia. CONCLUSION: Fiberoptic bronchoscopy is associated with decreased mesenteric blood flow, which may place the patient at risk for mesenteric ischemia and gastrointestinal bacterial translocation.

[Effect of dynamic hyperinflation on exertional dyspnea, exercise performance and quality of life in COPD]. / KOAH'da dinamik hiperinflasyonun egzersiz dispnesi, egzersiz kapasitesi ve yasam kalitesine etkisi.

There is increasing evidence that dynamic hyperinflation (DH) have negative effects on exercise performance and quality of life in chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to investigate effect of dynamic hyperinflation on exertional dyspnea, exercise performance and quality of life in patients with COPD. 72 clinically stable patients with moderate to severe COPD and 30 healthy age-matched control subjects were included in this study. Pulmonary function tests including lung volumes and maximal respiratory muscle forces, arterial blood gas analyses, evaluation of exertional dyspnea with the Borg scale, and The Saint George Respiratory Questionnaire (SGRQ, Turkish version) were performed at rest and after a 6-min walk test. We measured the change in inspiratory capacity (AlphaIC) after exercise to reflect DH. 80% of patients with COPD significantly decreased IC after exercise (DH). AlphaIC were -0.27 +/- 0.26 L in COPD and 0.8 +/- 0.17 L in controls (p= 0.001). A stepwise multiple regression analysis showed that to be a patient with COPD, Basal Dyspnea Index (BDI) and AlphaIC were the best predictors of 6 MWD (r(2)= 0.53, p< 0.001). FEV1 added an additinal 9% to the variance in 6 MWD. Exertional dyspnea (AlphaBorg) correlated with AlphaIC (r= -0.44, p= 0.0001) and BDI (r= 0.34, p= 0.02). AlphaIC significantly correlated with symptom (r= -0.36, p= 0.008), activity (r= -0.31, p= 0.03) and total scores (r= -0.30, p= 0.04) of SGRQ. Dynamic hyperinflation can often occur during exersice in patients with COPD. Extent of dynamic hyperinflation could able to explain exercise capacity limitation, exercise dyspnea, and poor quality of life in patients with COPD.

[Predictive factors associated with severity of asthma exacerbations]. / Astim ataklarinda agirligi belirleyici risk faktörleri.

Several factors have been accused for asthma exacerbations, however, very few studies have evaluated whether different factors predict severity of asthma exacerbation. We aimed to determine the predictive factors for severity of asthma exacerbation. Retrospective analysis of data on 93 patients visited our emergency-department because of asthma exacerbation was reviewed. Hospitalization in intensive care unit and/or intubation because of asthma was accepted as the criteria for severe exacerbation. Logistic regression analysis estimated the strength of association of each variable, potentially related to severe asthmatic exacerbation, with severe/very severe as compared to mild/moderate asthmatic exacerbation. Independent variables included in the analysis were age, sex, smoking history, inhaler steroid using, compliance with medication, chronic asthma severity, presence of additional atopic diseases, prick test positivity, provocative factors, number of short-acting beta(2)-agonist using, number of visits to emergency department for asthma over one year period, previous severe exacerbation, pulmonary functions, and blood eosinophil count. 20 were severe/very severe and 73 mild/moderate asthmatic exacerbation. Frequent using of short-acting beta(2)-agonist (OR= 1.5, 95% CI= 1.08-5.3, p= 0.003), noncompliance with medication (OR= 3.6, 95% CI= 1.3-9.9, p= 0.013), previous severe asthmatic exacerbation (OR= 3.8, 95% CI= 1.48-10.01, p= 0.005) and recent admission to hospital (OR= 2.9, 95% CI= 1.07-8.09, p= 0.037) were found to be predictive factors for severe asthmatic exacerbation. Different predictive factors, in particular frequent using of short-acting beta(2)-agonist and noncompliance with medication may be associated with severe asthma exacerbations compared to milder exacerbations. This suggests different mechanisms are responsible for severity of asthma exacerbation.

Relationship between airway colonization, inflammation and exacerbation frequency in COPD.

RATIONALE: To evaluate bacterial colonization and the airway inflammatory response, and its relationship to the frequency of exacerbation in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: Quantitative bacteriologic cultures, neutrophil elastase, myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-8 were measured in bronchoalveoler lavage (BAL) in 39 patients with stable COPD [19 with frequent exacerbation (> or = 3/year), and 20 with infrequent] and in 18 healthy controls (10 smokers and 8 non-smokers). RESULTS: BAL revealed the microorganisms with potential pathogenicity above the established threshold (> or = 10(3)cfu/ml) in 68.4% of patients with frequent exacerbation, 55% of infrequent exacerbation, 40% of smokers and 12.5% of non-smokers controls (P=0.05). BAL MPO, IL-8 and TNF-alpha levels were found to be significantly higher in COPD as compared to controls (P=0.001). However, only IL-8 level was significantly higher in COPD patients with frequent exacerbation as compared to infrequent (P=0.001). Airway bacterial load correlated with levels of airway inflammation markers in COPD (P<0.05). CONCLUSION: The bacterial load and airway inflammation contributes to each other in stable COPD. However, there is a link only between interleukine (IL)-8 and frequent exacerbations. Clearly, the relationship between bacterial colonization, airway inflammation and frequent exacerbations is of major importance in understanding of the COPD pathogenesis.

N-acetylcysteine protects the rats against phrenic nerve dysfunction in sepsis.

This study investigates the association of oxidative stress with the function of the phrenic nerve and inquires whether N-acetylcysteine (NAC) may counteract the possible detrimental effects. Thirty rats were divided into three groups: sham, cecal ligation and puncture (CLP), and CLP plus NAC treatment. Sepsis was produced by the CLP procedure. NAC was administered at 70 mg/day for 7 days. Electrophysiology was evaluated by the needle electromyography of the diaphragm and phrenic nerve conduction study. Oxidative stress was evaluated by malondialdehyde (MDA), nitrite/nitrate (NN), and reduced-glutathione (ReGSH) levels and myeloperoxidase (MPO) and catalase (CAT) activities in the phrenic nerve. In the CLP group, ReGSH and CAT were decreased (P = 0.0001, P = 0.07, respectively); and MDA, MPO, and NN were increased (P = 0.02, P = 0.0001, P = 0.043, respectively), compared with the sham group. NAC administration increased the ReGSH (P = 0.036) and decreased the MDA, MPO, and NN (P = 0.008, P = 0.01, P = 0.032, respectively), compared with the CLP group. In the CLP group, electrophysiology revealed reductions in the number of motor unit action potentials (P = 0.0001) and prolongations in the latency of the compound nerve action potential (P = 0.0001), indicating phrenic nerve neuropathy. NAC administration significantly ameliorated these electrophysiological alterations (P = 0.011, P = 0.0001, respectively), compared with the CLP group. The present results showed that intraabdominal sepsis is closely associated with phrenic nerve neuropathy. In addition, NAC administration protects the rats against the detrimental events of sepsis.

Cough headache: frequency, characteristics and the relationship with the characteristics of cough.

Cough headache (CH) is a relatively rare, but an important complication of cough. The aim of this cross-sectional clinical study was to evaluate the frequency, characteristics and etiology of CH among the patients referred to our Outpatient Department with the complaint of cough, and to investigate the relationship between their cough and headache characteristics. We evaluated 96 females and 69 males, a total of 165 patients with cough. Among those, 57 patients (34.5%) had one or more cough complications and 32 patients (19.3%) were diagnosed as CH. Although it was known that most of the patients with CH had benign headache characteristics, the ratio of the symptomatic CH was not low (37.5% of the CH patients and 7% of patients with cough). Also, there was a significant correlation between the frequency of cough and the severity of headache. Logistic regression analysis showed that the incidence of CH was increased 0.4-fold, when frequency of cough increased. Age, sex, tobacco use ad the duration of cough were not found to be predictive factors for CH. Logistic regression analysis showed that the rate of cough complications increased 2.08-fold, when the duration of cough was longer than eight weeks (p=0.03) and 0.4-fold when the frequency of cough increased (p=0.02). In conclusion, CH is a relatively rare, but an important complication of cough and it commonly has an effective treatment available. Radiological work-up was crucial in ruling out other causes of headache and to confirm that the CH was truly benign.

Systolic pulmonary artery pressure and serum uric acid levels in patients with hyperthyroidism.

BACKGROUND: The aim of this study was to investigate systolic pulmonary artery pressure (SPAP) and serum uric acid (SUA) levels in patients with hyperthyroidism and after euthyroid state was reached. METHODS: Twenty five (10 male, 15 female, mean age 49.8 +/- 11.6 years) consecutive patients with hyperthyroidism (18 due to toxic nodular goiter, seven to Graves' disease) and 25 (eight male, 17 female, mean age 48.7 +/- 8.7 years) healthy controls were included in the study. Thyroid hormones, SUA, glucose, urea, creatinine, and transthoracic echocardiography were performed in all patients. All tests were repeated after treatment of hyperthyroidism. RESULTS: Mean SPAP and SUA levels in patients with hyperthyroidism were significantly higher than in controls (30.4 +/- 8.5 vs. 22 +/- 3.7 mmHg, p <0.0001, and 5.1 +/- 1.1 vs. 4.3 +/- 0.5 mg/dL, p = 0.004, respectively). Elevated SPAP and SUA levels in patients with hyperthyroidism decreased significantly after treatment to levels comparable with controls (24.4 +/- 5.4 mmHg, p = 0.001 and 4.6 +/- 0.9 mg/dL, p = 0.002, respectively). Correlation between SPAP and SUA levels, however, was not significant in hyperthyroid population and after euthyroid stage was reached (r = 0.34, p = 0.097, and r = 0.256, p = 0.216, respectively), possibly due to relatively low number of patients (overall correlation of SPAPs and SUAs was r = 0.4, p <0.0001). CONCLUSIONS: Hyperthyroidism should be included in differential diagnosis of pulmonary arterial hypertension. However, further investigations are needed to determine the exact mechanism between hyperthyroidism and pulmonary hypertension.

The effects of hormone replacement therapy type on pulmonary functions in postmenopausal women.

OBJECTIVE: To study whether hormone replacement therapy (HRT) or Tibolone has an effect on pulmonary function in postmenopausal women. METHODS: Seventy-five postmenopausal women without any risk factor for pulmonary disease were included in this randomized, prospective study. Fifty women had undergone natural menopause and 25 had had a hysterectomy/ooforectomy. Twenty-five natural menopause women were randomly allocated to two groups: 25 patients (Group I) were treated with Tibolone 2.5 mg/day, 25 patients (group II) with Estradiol Hemihidrate 2 mg+Norethindron Asetate 1 mg/day. Twenty-five induced menopause women were treated with 17 beta-estradiol 2 mg/day. Lung function tests including forced vital capacity (FVC), forced expiratory volume (FEV(1)), FEV(1)/FVC, forced expiratory flow rate over the 25-75% of the forced vital capacity volume (FEF(25-75%)), and peak expiratory flow rate (PEF) were evaluated at the beginning and 3 months after the treatment to assess the effects of HRT and Tibolone on respiratory function. RESULTS: Regardless of HRT types a significant difference was observed in FVC and FEV(1) after 3 months of the therapy (P=0.001, 0.0001, respectively). No significant difference was found between pre and post therapy values in the other parameters (P>0.05). CONCLUSIONS: We determined a significant increase in FVC and FEV(1) parameters of pulmonary functions after 3 months of the therapy regardless of HRT types. Therefore, we think that HRT regimens have modifying effects on pulmonary function in postmenopausal women.

Bronchoscopy induces intestinal mucosal barrier dysfunction: a possible role for nitric oxide.

OBJECTIVE: This study investigates the effect of bronchoscopy on intestinal mucosal barrier function and its association with intestinal nitric oxide production. METHODS: 30 rats were used. The study group (n=15) underwent rigid bronchoscopy. At 24 h following bronchoscopy, ileal nitrite/nitrate levels were evaluated. The ileum was also examined for mucosal damage, and graded according Chiu's histologic injury scale. RESULTS: In the bronchoscopy group, the ileal nitrite/nitrate levels were significantly higher than those of controls (398.5 +/- 85.1 and 44.5 +/- 6.6 nmol/g tissue, respectively, P=0.001). In the bronchoscopy group, the mucosal damage was significant, compared with those of controls (mean ranks, 22.8 and 8.2, P<0.0001). The changes varied from denuded villi and dilated capillaries to significant architectural distortion, lamina propria disintegration, ulceration and hemorrhage. Significant correlation was found between ileal nitrite/nitrate levels and mucosal damage in the bronchoscopy group (rs=0.56, P=0.03). CONCLUSION: This study suggests that bronchoscopy induces intestinal mucosal barrier dysfunction in association with excess intestinal nitric oxide production. These events may be involved in mechanisms responsible for bacterial translocation after bronchoscopy.

Ventilator-associated pneumonia due to extensive drug-resistant Acinetobacter baumannii: risk factors, clinical features, and outcomes.

Acinetobacter baumannii is characterized by a rapid development of resistance to the commonly used antimicrobial agents. We investigated the risk factors, clinical features, and outcomes in ventilator-associated pneumonia (VAP) caused by extensive drug-resistant Acinetobacter baumannii (XDRAB). Clinical parameters and overall in-hospital mortality rates were compared between the VAP with and without XDRAB infection groups. This study showed that VAP caused by XDRAB was not associated with in-hospital mortality. However, it was related to high Simplified Acute Physiology Score II scores and increasing durations of hospital stays.

Indacaterol once-daily provides superior efficacy to salmeterol twice-daily in COPD: a 12-week study.

BACKGROUND: Indacaterol is a novel, inhaled once-daily ultra-long-acting ß(2)-agonist for the treatment of COPD. METHODS: This 12-week randomised, parallel-group study compared the efficacy of indacaterol 150 µg once-daily to salmeterol 50 µg twice-daily in patients with moderate-to-severe COPD. Assessments included FEV(1) standardised area under curve (AUC) from 5 min to 11 h 45 min at Week 12 (primary endpoint), 24-h trough FEV(1) (mean of 23 h 10 min and 23 h 45 min post-dose) at Week 12 (key secondary endpoint), FEV(1) and FVC measured over 24-h, transition dyspnoea index (TDI) and rescue medication use. RESULTS: Of 1123 patients randomised 92.1% completed. Mean ± SD age was 62.8±8.78 years, post-bronchodilator FEV(1) 51.8±12.32% predicted, FEV(1)/FVC 50.6±9.54%. At Week 12, FEV(1) AUC(5 min-11 h 45 min) for indacaterol was statistically superior (p<0.001) to salmeterol (adjusted mean difference [95% CI] 57 [35, 79] mL), as was 24-h trough FEV(1) (60 [37, 83] mL, p<0.001). Indacaterol also showed statistical superiority over salmeterol in terms of FEV(1) and FVC measured over 24-h at Week 12. For TDI at Week 12, the mean total score was statistically superior for indacaterol versus salmeterol (difference 0.63 [0.30, 0.97], p<0.001), as was the percentage of patients with a clinically relevant (i.e., ≥1 point) change from baseline (69.4% vs 62.7%, p<0.05). For rescue medication, patients on indacaterol used fewer puffs/day (difference -0.18 [-0.36, 0.00] puffs/day, p<0.05) and had a greater percentage of days with no rescue use (difference 4.4 [0.6, 8.2], p<0.05). CONCLUSION: Once-daily indacaterol provided statistically superior bronchodilation with an improvement in breathlessness and rescue use compared with twice-daily salmeterol. ClinicalTrials.gov NCT00821093.

Oxygen supplementation during airway instrumentation improves intestinal barrier dysfunction.

BACKGROUND/PURPOSE: The study investigates the effect of airway instrumentation on the histopathology of the intestine, contribution of bacterial translocation, and whether oxygen supplementation may counteract the possible detrimental effects of this procedure. METHODS: Fifty-five Wistar rats were assigned to 3 groups. Group 1 served as control. Groups 2 and 3 underwent airway instrumentation. In addition, group 3 received oxygen supplementation during the procedure. Arterial blood gases were measured after the procedure. Samples of mesenteric lymph nodes ileum, cecum, spleen, liver, and blood were harvested for determination of bacterial growth after 24 hours. Ileum was evaluated histologically. RESULTS: In group 2, the rats presented a decrease in oxygen saturation (90% +/- 0.3%, P < .0001), hypoxemia (PaO2, 73 +/- 1.5 mm Hg; P < .0001), and respiratory acidosis (pH 7.27 +/- 0.01; PaCO2, 48 +/- 1.5 mm Hg; P < .0001) after airway instrumentation. These rats also showed evidence of intestinal injury (P < .0001) and bacterial translocation to mesenteric lymph nodes in 10 of 20 rats compared with 0 of 15 in the controls (P = .004). In group 3, oxygen supplementation provided normal arterial blood gas parameters, and led to minimal histologic changes and bacterial translocation in only 1 of 20 rats, compared with group 2 (P < .0001 and P = .005, respectively). CONCLUSIONS: The study suggests that oxygen supplementation during airway instrumentation prevents hypoxemia, intestinal damage, and bacterial translocation.

Effects of triazolopyrimidine on lipid peroxidation and nitric oxide levels in the corticosteroid-impaired healing of rat tracheal anastomoses.

Corticosteroids are used to reduce the oedema and prevent scar tissue formation of the upper airways by their ability to inhibit influx of inflammatory cells, limit capillary permeability and block collagen synthesis in the early stages of wound healing. Triazolopyrimidine (Trapidil) is an antiplatelet agent that acts in part as a phosphodiesterase inhibitor and as a competitive inhibitor of the platelet-derived growth factor (PDGF) receptor. Trapidil, with its vasodilator and NO releasing effect may have some potential to diminish the tissue injury. This study was carried out to evaluate the effects of trapidil (triazolopyrimidine) on lipid peroxidation and nitric oxide in the corticosteroid-impaired healing of tracheal anastomoses. Thirty-four adult Wistar rats were divided into five groups. The animals underwent tracheal transection and primary anastomoses. The groups were assigned as follows: group I, control, (GI, n = 6); group II, sham, (GII, n = 6); group III, dexamethasone, 0.1 mg kg(-1) twice daily intramuscularly, (GIII, n = 8); group IV, trapidil, 6 mg kg(-1) twice daily intraperitoneally (GIV, n = 7); group V, dexamethasone, 0.1 mg kg(-1) plus trapidil, 6 mg kg(-1) twice daily (GV, n = 7), for 1 week. After 1 week, anastomotic healing was assessed by measurement of bursting pressure, evaluation of histopathology, measurement of MDA and nitrite/nitrate levels. In GIII, GIV and GV bursting pressures resulted in significantly reduced anastomotic strength compared to the controls (p < 0.001 for all groups). The difference between bursting pressures of GIII and GIV was not found to be statistically significant (p = 0.966). In regard to fibroblast proliferation and collagen content, a significant difference was found between GIII and GI (p < 0.01), A significant difference was also found when GIV and GV were compared to GIII (p < 0.01). MDA and nitrite/nitrate levels were found to be higher in GIII when compared to all other groups. MDA levels of GIV and GV rats were found to be lower than GIII (p < 0.001, for both groups). The nitrite/nitrate levels of GIV and GV rats were found to be lower than GIII (p < 0.05), and higher than GI (p < 0.001). Trapidil may be useful for its preventive effects on lipid peroxidation and possible increases in NO in cases with corticosteroid-impaired healing of trachea anastomoses.

Gut decontamination prevents bronchoscopy-induced bacterial translocation. An experimental study in rats.

BACKGROUND: Selective gut decontamination is suggested to suppress the gram-negative bacterial overgrowth in the intestine and consequently to reduce bacterial translocation. OBJECTIVE: The purpose of the present study is to examine the effects of gut decontamination on bronchoscopy-induced bacterial translocation, and intestinal mucosal injury. METHODS: Forty-five rats were assigned into three groups. Group 1 served as control (n=15). Group 2 (n=15) and group 3 (n=15) underwent bronchoscopy. In addition, group 3 underwent gut decontamination. Gut decontamination was performed two days prior to bronchoscopy with erythromycin and neomycin. Twenty-four hours after bronchoscopy, blood, mesenteric lymph nodes, spleen, liver, ileum and cecum were harvested for bacterial determination. The ileum was also assessed and graded histologically according to Chiu's injury scale. RESULTS: In the bronchoscopy group, bacterial translocation to the mesenteric lymph nodes was found in 7/15 rats (46.7%), compared to none of the controls (p=0.01). These rats also showed significant evidence of intestinal injury, compared to the controls (mean ranks, 32.7 or 8.5, p<0.0001). On the other hand, gut decontamination prevented bacterial translocation, compared to the bronchoscopy group (p=0.011). However, gut decontamination provided no beneficial effect on the intestinal mucosal injury, compared to the bronchoscopy group. These animals also revealed significant intestinal injury, compared to the controls (mean ranks, 27.8 or 8.5, p<0.0001). CONCLUSIONS: Our data shows that despite no amelioration in bronchoscopy-induced intestinal mucosal injury, gut decontamination has a preventive role for bronchoscopy-induced bacterial translocation.

Electrophysiological and histopathological evaluation of respiratory tract, diaphragm, and phrenic nerve after dichlorvos inhalation in rats.

The aim of this study was to investigate the dose-related effects of dichlorvos inhalation on electrophysiological alterations of diaphragm and phrenic nerve and the changes in the histologic structure of respiratory system. This study was performed on 33 rats divided into 5 groups, inhaling 1, 2, 5, 10, and 15 microg/L of dichlorvos, respectively. Electrodiagnostic investigations of diaphragm and phrenic nerve were made before and after inhalations. Aspiration samples were taken from lungs to evaluate the presence of infection agents. The airways, lungs, and diaphragms were dissected out for histologic investigation. Rats exposed to a low concentration of dichlorvos (1-5 microg/L) showed no symptoms of intoxication, but exposure to higher doses (10-15 microg/L) induced dyspnea in several animals. Lower doses of dichlorvos revealed no electromyographic changes on diaphragm, whereas higher doses revealed a clear neuropathic involvement. Delayed phrenic nerve motor conduction velocity was noted for each group (p <.05). Morphologic changes on the tracheal epithelium, hyperplasia, thickening of the blood-air barrier, degeneration in alveoli, and ductus alveolaris were seen in histopathologic investigation. In conclusion, the acute inhalation of dichlorvos caused clear evidence of neuropathic involvement of the diaphragm and the phrenic nerve. Also, toxic pneumonitis and injury to the tracheal epithelial were noticed.

The effects of corticosteroids on the healing of tracheal anastomoses in a rat model.

The deleterious effects of corticosteroids on anastomotic healing have been widely demonstrated in various tissues. This study is designed to investigate the effects of corticosteroids on the healing of tracheal anastomoses. Forty-two adult female Wistar rats, randomly divided into five groups, underwent tracheal transection and primary anastomoses. The groups were assigned as follows: Group I, sham, ( N= 6); Group II, control, ( N= 6); Group III, dexamethasone, 0.1 mg kg (-1) per day, intramuscularly for a week ( N= 10); Group IV, dexamethasone, 1 mg kg (-1) per day, intramuscularly for a week (N= 10); Group V, dexamethasone, 6 mg kg (-1) intramuscularly as a single dose ( N= 10). After 7 days, anastomotic healing was assessed by measurement of bursting pressure and hydroxyproline content. Histological examination was performed according to the modified Ehrlich/Hunt scale. The bursting pressure was significantly decreased in Group III and Group IV when compared to the control group (P< 0.0001 for both groups). There was also significance between the bursting pressures of Group III and Group IV (P< 0.01). However, the difference failed to reach significance between Group V and the control group. The reduction of bursting pressure was not reflected in diminished hydroxyproline content. The hydroxyproline content of the study groups (GIII, GIV and GV) were not statistically different compared with the control group. Except for inflammatory cell infiltration, histological parameters including epithelial regeneration, fibroblast proliferation, collagen content, and angiogenesis also demonstrated significant differences among the groups (P< 0.05). The present study demonstrates that daily administration of dexamethasone for a week significantly impairs the healing of tracheal anastomoses in a dose-dependent manner while a single-dose postoperatively does not affect the healing process.

The effects of dexamethasone on lipid peroxidation and nitric oxide levels on the healing of tracheal anastomoses: an experimental study in rats.

Corticosteroids are shown to have deleterious effects on wound healing for various tissues. Arginine metabolism and nitric oxide (NO) synthesis play an important role in many aspects of inflammation and wound healing. The study was designed to evaluate the relationship of dexamethasone impaired healing of tracheal anastomoses to NO metabolism and lipid peroxidation. Forty-two adult Wistar rats were randomly divided into five groups. The animals underwent tracheal transection and primary anastomoses. The groups were assigned as follows: Group I (GI) (sham, N = 6); Group II (GII) (control, N = 6); Group III (GIII), dexamethasone, 0.1 mg kg(-1) per day, intramuscularly for a week (N = 10); Group IV (GIV), dexamethasone, 1 mg kg(-1) per day, intramuscularly for a week (N = 10); Group V (GV), dexamethasone, 6 mg kg(-1) intramuscularly as a single dose (N = 10). After 7 days, bursting pressure was used to evaluate anastomotic healing. Serum nitrite/nitrate and malondialdehyde (MDA) levels were measured as an index of NO synthesis and lipid peroxidation, respectively. The bursting pressure significantly decreased in GIII and GIV when compared to the control group. The difference between GIII and GIV was also statistically significant. Nitrite/nitrate and MDA levels of GIII were found to be significantly higher than the control group. Also, the difference was found to be statistically significant between GIII and GIV in regard to nitrite/nitrate levels. The present study demonstrates that daily administration of dexamethasone for a week inhibits NO synthesis in a dose-dependent manner on tracheal anastomotic healing. Besides the generally accepted evaluation parameters including bursting pressure and hydoxyproline content; NO and MDA levels may be helpful in the assessment of wound healing especially for the investigation of impairment mechanism.