聚维酮碘诱导兔胸膜黏连的机制研究

目的：本研究旨在建立iodopovidone（Betadine,聚维酮碘）诱导兔胸膜黏连模型,并探讨其作用机制。方法： 4组28只新西兰大白兔在放置胸导管后,分为4组：第1组给予2% iodopovidone 2 mL胸腔内注射。第2组给予4％iodopovidone 2 mL胸腔内注射。第3组在胸腔内注入4％iodopovidone 2 mL 24 h前及其后每周1次予以肌肉注射0.8 mg/kg 曲安西龙,连续2周,作为iodopovidone激素干预组。第4组给予多西环素10 mg/kg胸腔内注射作为阳性对照组。在iodopovidone或多西环素注射后的24、48、72 h分别收集胸腔积液并计量,测定胸水中白细胞计数、蛋白及乳酸脱氢酶（LDH）。2周后杀死兔子并作胸膜黏连评分,行HE染色、经第Ⅷ因子免疫组化染色对胸膜组织中炎症和血管新生程度做定量分析。结果： Iodopovidone激素干预组所产生的胸水量、胸水中白细胞总数均显著低于2%或4％iodopovidone组和多西环素对照组（P<0.05）。2% iodopovidone组胸膜黏连评分为7.00±1.29,4% iodopovidone组胸膜黏连评分为7.71±0.76,多西环素对照组胸膜黏连评分为7.14±0.90,3组间无显著差异（P>0.05）,而iodopovidone激素干预组胸膜黏连评分为3.71±1.98,均显著低于2%或4％iodopovidone组和多西环素对照组（P<0.05）。2% iodopovidone组胸膜组织中血管新生密度为5.08%±0.92%,4% iodopovidone组为6.29%±0.60%,多西环素对照组为6.86%±2.20%,激素干预组的胸膜炎症反应及胸膜组织中血管新生密度（2.29%±0.60%）显著低于iodopovidone 和阳性对照组（P<0.05）。结论： Iodopovidone能诱导兔胸膜黏连模型,皮质激素能明显抑制其黏连效果,提示胸膜炎症反应在iodopovidone的胸膜黏连机制中可能起重要的作用。     

Effectiveness and safety of outpatient pleurodesis in patients with recurrent malignant pleural effusion and low performance status

OBJECTIVES:

To evaluate the effectiveness and safety of pleurodesis carried out entirely on an outpatient basis in patients with recurrent malignant pleural effusions and Karnofsky Performance Status scores ≤70.

METHODS:

This study was a prospective trial comprising patients with symptomatic recurrent malignant pleural effusion and Karnofsky Performance Status scores ≤70 but >30. All selected patients underwent pleural catheter placement (14 Fr) in an outpatient facility. When chest radiography revealed post‐drainage lung expansion of >90%, pleurodesis (3 g of talc) was performed. Catheters were maintained until the daily output was <100 mL/day. The patients were evaluated in the first month and every three months thereafter for fluid recurrence, the need for additional procedures, and complications.

RESULTS:

During the study period (January 2005 to July 2007), 64 patients (24 men, 40 women), with an average age of 61.4 years, underwent elective chest tube drainage. Primary sites of the underlying malignancy were breast (27), lung (22), and others (15). Sixty‐six pleural catheters were placed (bilaterally in 2 patients), and 52 talc pleurodesis procedures were performed. Fourteen patients had a trapped lung and were excluded from the trial. No complications were observed during catheter placement or pleurodesis. Post‐pleurodesis complications included catheter obstruction (4 patients) and empyema (1). The average drainage time was 9.9 days. The recurrence rate observed in patients that were alive 30 days after pleurodesis was 13.9% (5/36 patients). Six patients required additional procedures after the pleurodesis. The average survival time was 101 days.

CONCLUSION:

In this study, talc pleurodesis was safely performed in an outpatient setting with good efficacy and a reasonable complication rate, thereby avoiding hospital admission.     

Inflammation and clinical repercussions of pleurodesis induced by intrapleural talc administration

Although reports on pleurodesis date back to the beginning of the 20th century, the search for the ideal sclerosing agent is ongoing. Several agents have been studied and used, but talc continues to be the most popular. However, potentially harmful systemic side effects have been associated with talc pleurodesis. In this article we discuss the likely mechanisms of pleural inflammation and pleurodesis with emphasis on the systemic response due to the instillation of talc into the pleural space.     

Serum and Pleural Fluid Procalcitonin in Predicting Bacterial Infection in Patients with Parapneumonic Effusion

This study evaluated the value of procalcitonin (PCT) levels in pleural effusion to differentiate the etiology of parapneumonic effusion (PPE). Forty-one consecutive PPE patients were enrolled and were divided into bacterial and non-bacterial PPE. Blood and pleural effusion samples were collected for PCT measurement on admission and analyzed for diagnostic evaluation. PCT of pleural fluid was significantly increased in the bacterial PPE group (0.24 ng/mL) compared to the non-bacterial PPE group (0.09 ng/mL), but there was no significant difference for serum PCT. A PCT concentration of pleural fluid >0.174 ng/mL (best cut-off value) was considered positive for a diagnosis of bacterial PPE (sensitivity, 80%; specificity, 76%; AUC, 0.84). Pleural effusion PCT in the bacterial PPE is significantly different from those of the non-bacterial PPE and control groups, so the diagnostic use of PCT still warrants further investigation.     

Role of the Neutrophil-Lymphocyte Ratio in the Differential Diagnosis of Exudative Pleural Effusion

OBJECTIVES:Pleural effusion is a common diagnostic and clinical problem. The differential diagnosis of pleural effusion may be difficult and may require several procedures, including invasive ones. Certain studies have investigated biochemical parameters to facilitate the diagnosis of exudative pleural effusion; however, it remains a challenging problem in clinical practice. We aimed to investigate the potential role of the neutrophil-lymphocyte ratio, which can be easily obtained by determining the cell count of the pleural fluid, in the differential diagnosis of exudative pleural effusion.METHODS:Records from patients who underwent thoracentesis and pleural fluid analysis between May 1, 2013, and March 1, 2015, were obtained from the electronic database of our hospital. The patients who met the inclusion criteria were divided into five groups according to their diagnosis: malignant pleural effusion, para-malignant pleural effusion, para-pneumonic effusion, tuberculosis-related effusion or other. The neutrophil-lymphocyte ratio value was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The patient groups were compared according to the given parameter.RESULTS:A total of 465 patients who met the inclusion criteria among 1616 patients with exudative pleural effusion were included in the study. The mean neutrophil-lymphocyte ratio value was significantly lower in tuberculosis-related pleural effusion compared to malignant, para-pneumonic and para-malignant effusions (p=0.001, p=0.001, p=0.012, respectively). The areas under the curve for tuberculosis pleurisy compared to malignant, para-pneumonic and para-malignant effusions were 0.38, 0.36, and 0.37, respectively. Lower cut-off values had higher sensitivity but lower specificity for tuberculosis pleurisy, while higher cut-off values had higher specificity but lower sensitivity for this condition.CONCLUSION:The pleural fluid neutrophil-lymphocyte ratio, which is an inexpensive, reproducible, and easily calculated hematological parameter, may facilitate the differential diagnosis of pleural effusion.     

Impact of Implementation of an Automated Liquid Culture System on Diagnosis of Tuberculous Pleurisy

This study was conducted to evaluate the impact of implementation of an automated liquid culture system on the diagnosis of tuberculous pleurisy in an HIV-uninfected patient population. We retrospectively compared the culture yield, time to positivity, and contamination rate of pleural effusion samples in the BACTEC Mycobacteria Growth Indicator Tube 960 (MGIT) and Ogawa media among patients with tuberculous pleurisy. Out of 104 effusion samples, 43 (41.3%) were culture positive on either the MGIT or the Ogawa media. The culture yield of MGIT was higher (40.4%, 42/104) than that of Ogawa media (18.3%, 19/104) (P<0.001). One of the samples was positive only on the Ogawa medium. The median time to positivity was faster in the MGIT (18 days, range 8-32 days) than in the Ogawa media (37 days, range 20-59 days) (P<0.001). No contamination or growth of nontuberculous mycobacterium was observed on either of the culture media. In conclusion, the automated liquid culture system could provide approximately twice as high yields and fast results in effusion culture, compared to solid media. Supplemental solid media may have a limited impact on maximizing sensitivity in effusion culture; however, further studies are required.

Graphical Abstract

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Haematological changes and free-radical involvement in an experimental foot-pad oedema model

A foot-pad oedema model was used to investigate some early peripheral blood changes associated with the development of an acute inflammatory response. The inflammatory model used was an example of a cell-mediated hypersensitivity reaction. Male rats were inoculated in the scruff with Freund's Complete Adjuvant (FCA) on day 0 and then challenged 6 days later with FCA in one hind paw. An acute inflammatory reaction was initiated over the following 72 hours. Within 8 hours of induction a significant increase in neutrophils was detected in the peripheral blood reaching peak levels at 24 hours. The peak level of monocytes was not seen until 48 hours after challenge. Lymphocyte numbers, haemoglobin and haematocrit values all remained within the normal range. Plasma iron levels fell by approximately 85% within 24 hours whereas plasma -1-acid glycoprotein and the copper-containing protein caeruloplasmin were found to increase steadily throughout the development of the inflammatory response. These findings are discussed in relation to previously published work using the same model. An important inter-relationship between phagocytic cells, iron and free radical production at the site of the acute inflammatory reaction is suggested.     

Reduced expression of transforming growth factor beta 1 exacerbates pathology in an experimental asthma model

Allergic asthma is characterized by airway hyperreactivity (AHR), eosinophilic airway inflammation and elevated serum IgE levels. T-helper 2 (Th2) cells play a critical role in the pathogenesis of asthma, but the immunological mechanisms that inhibit Th2 cell function in vivo are not well understood. Conflicting results regarding the protective role of Th1 cytokines and TGF-beta in asthma have been reported. To further investigate the role of TGF-beta(1 )in asthma, we examined mice heterozygous for deletion of the TGF-beta(1) gene (TGF-beta(1) (+/-) mice) in a murine asthma model. While TGF-beta(1) (+/-) mice seem phenotypically normal, they express only about 30% of wild type TGF-beta(1) protein levels as shown before. The reduced expression of TGF-beta(1) is accompanied by a strikingly increased eosinophilic inflammation and mucus secretion in response to ovalbumin (OVA) sensitization. Moreover, TGF-beta(1) (+/-) mice develop significantly enhanced Th2-cytokine levels, decreased IFN-gamma production and increased levels of OVA-specific IgE in serum. In contrast, AHR in response to methacholine is not altered significantly. Our data demonstrate that reduced expression of TGF-beta(1) exacerbates pathology in an experimental asthma model and support the view that the elevated levels of TGF-beta(1) in asthmatic airways might be, at least in part, a result of anti-inflammatory compensation by this cytokine.     

Factors influencing residual pleural opacity in tuberculous pleural effusion

Tuberculous pleural effusion (TPE) leads to residual pleural opacity (RPO) in a significant proportion of cases. The aim of this study was to investigate which TPE patients would have RPO following the treatment. This study was performed prospectively for a total of 60 TPE patients, who underwent pleural fluid analysis on the initial visit and chest radiographs and computed tomography (CT) scans before and after the administration of antituberculous medication. At the end of antituberculous medication, the incidence of RPO was 68.3% (41/60) on CT with a range of 2-50 mm. Compared with the non-RPO group, the RPO group had a longer symptom duration and lower pleural fluid glucose level. On initial CT, loculation, extrapleural fat proliferation, increased attenuation of extrapleural fat, and pleura-adjacent atelectasis were more frequent, and parietal pleura was thicker in the RPO group compared with the non-RPO group. By multivariate analysis, extrapleural fat proliferation, loculated effusion, and symptom duration were found to be predictors of RPO in TPE. In conclusion, RPO in TPE may be predicted by the clinico-radiologic parameters related to the chronicity of the effusion, such as symptom duration and extrapleural fat proliferation and loculated effusion on CT.     

Effect of acute ethanol treatment on biochemical and histopathological factors in rat liver in an experimental sepsis model

The aim of this study was to investigate the contribution of acute alcohol in sepsis-related liver damages using a Cecal Ligation and Puncture (CLP) model. Rats were divided into 7 groups (5 rats/group): control (saline-injected), sham-operated, CLP, ethanol (1.0 and 2.0 g/kg b.w) and CLP+ethanol. The CLP+ethanol group received a single dose of ethanol following sepsis induction. Sepsis induction caused early changes in lipid peroxidation products in liver, whereas ethanol alone (2.0 g/kg b.w) resulted in a significant increase (~21%) in lipid peroxidation, which was further increased (~57%) in CLP rats treated with alcohol. CLP operation and alcohol treatment exhibited additive effects on plasma catalase, liver glutathione and glutathione S-transferase (GST), which were primarily suppressed due to ethanol. Hepatic cytochrome P4501A1, which was elevated in CLP rats, was reversed in the CLP+ethanol group. Plasma tumor necrosis factor-α was markedly elevated (~85%) in septic rats, but was unaffected in septic rats having received ethanol. Histopathological observations revealed that inflammatory reactions in liver in response to CLP operation are not intensified by ethanol administration. On the basis of biochemical and histopathological results, it can be concluded that acute ethanol treatment is responsible for early changes in oxidative stress, which may lead to polymicrobial sepsis-related organ damage.     

A case of leukemic pleural infiltration in atypical chronic myeloid leukemia

Pleural effusion in chronic myeloid leukemia (CML) is poorly understood and rarely reported in the literature. When the pleural effusion is caused by leukemic pleural infiltration, the differential white blood cell count of the effusion is identical to that of the peripheral blood, and the fluid cytology reveals leukemic blasts. We report here a case of bilateral pleural involvement of atypical CML in an 83-yr old male diagnosed with pancreatic cancer with abdominal wall metastasis and incidental peripheral leukocytosis. Based on bone marrow examination, chromosome analysis and polymerase chain reaction he was diagnosed with Philadelphia chromosome negative, BCR/ABL gene rearrangement negative CML. Following 3 months of treatment with gemcitabine for pancreatic cancer, he developed bilateral pleural effusions. All stages of granulocytes and a few blasts were present in both the pleural fluid and a peripheral blood smear. After treatment with hydroxyurea and pleurodesis, the pleural effusion resolved.     

(Central) Auditory Processing: the impact of otitis media

OBJECTIVE:

To analyze auditory processing test results in children suffering from otitis media in their first five years of age, considering their age. Furthermore, to classify central auditory processing test findings regarding the hearing skills evaluated.

METHODS:

A total of 109 students between 8 and 12 years old were divided into three groups. The control group consisted of 40 students from public school without a history of otitis media. Experimental group I consisted of 39 students from public schools and experimental group II consisted of 30 students from private schools; students in both groups suffered from secretory otitis media in their first five years of age and underwent surgery for placement of bilateral ventilation tubes. The individuals underwent complete audiological evaluation and assessment by Auditory Processing tests.

RESULTS:

The left ear showed significantly worse performance when compared to the right ear in the dichotic digits test and pitch pattern sequence test. The students from the experimental groups showed worse performance when compared to the control group in the dichotic digits test and gaps-in-noise. Children from experimental group I had significantly lower results on the dichotic digits and gaps-in-noise tests compared with experimental group II. The hearing skills that were altered were temporal resolution and figure-ground perception.

CONCLUSION:

Children who suffered from secretory otitis media in their first five years and who underwent surgery for placement of bilateral ventilation tubes showed worse performance in auditory abilities, and children from public schools had worse results on auditory processing tests compared with students from private schools.     

Effectiveness of an aquatic exercise program and low-level laser therapy on articular cartilage in an experimental model of osteoarthritis in rats

Objective: The aim of this study was to evaluate the effects of an aquatic exercise program and low-level laser therapy (LLLT) (associated or not) on degenerative modifications and inflammatory mediators on the articular cartilage using an experimental model of knee OA. Method: Forty male Wistar rats were divided into 4 groups: knee OA – without treatment (OA); OA plus exercise program group (OAE); OA plus LLLT (OAL); OA plus exercise program associated with LLLT (OAEL). Trained rats performed a water-jumping program carrying a load equivalent to 50-80 % of their body mass strapped to their chest. The laser irradiation was used either as the only method or after the exercise training had been performed, at 2 points contact mode (medial and lateral side of the left joint). The treatments started 4 weeks after the surgery, 3 days/week for 8 weeks. Results: The results revealed that all treated groups (irradiated or not) exhibited a better pattern of tissue organization, with less fibrillation and irregularities along the articular surface and improved chondrocytes organization. Also, a lower cellular density and structural damage (OARSI score) and higher thickness values were observed in all treated groups. Additionally, OAE and OAEL showed a reduced expression in IL-1β and caspase-3 as compared with OA. Furthermore, a statistically lower MMP-13 expression was only observed in OAEL as compared with OA. Conclusion: These results suggest that aquatic exercise program and LLLT were effective in preventing cartilage degeneration. Also, physical exercise program presented anti-inflammatory effects in the knees in OA rats.     

Serum vascular endothelial growth factor in pediatric patients with community-acquired pneumonia and pleural effusion

This study investigated the serum vascular endothelial growth factor (VEGF) levels in children with community-acquired pneumonia. Serum VEGF levels were measured in patients with pneumonia (n=29) and in control subjects (n=27) by a sandwich enzyme-linked immunosorbent assay. The pneumonia group was classified into bronchopneumonia with pleural effusion (n=1), bronchopneumonia without pleural effusion (n=15), lobar pneumonia with pleural effusion (n=4), and lobar pneumonia without pleural effusion (n=9) groups based on the findings of chest radiographs. We also measured serum IL-6 levels and the other acute inflammatory parameters. Serum levels of VEGF in children with pneumonia were significantly higher than those in control subjects (p<0.01). Children with lobar pneumonia with or without effusion showed significantly higher levels of serum VEGF than children with bronchopneumonia. For lobar pneumonia, children with pleural effusion showed higher levels of VEGF than those without pleural effusion. Children with a positive urinary S. pneumonia antigen test also showed higher levels of VEGF than those with a negative result. Serum IL-6 levels did not show significant differences between children with pneumonia and control subjects. Serum levels of VEGF showed a positive correlation with the erythrocyte sedimentation rate in the children with pneumonia. In conclusion, VEGF may be one of the key mediators that lead to lobar pneumonia and parapneumonic effusion.     

A new model of experimental parotitis in rats and its implication for trigeminal nociception

A rat model of chronic parotitis was developed following a direct injection of Complete Freund's adjuvant (CFA) into the unilateral parotid gland via the parotid duct without skin incision. The nocifensive behavior, plasma extravasation in the parotid gland, and trigeminal Fos protein expression, a marker of neuronal activation, were analyzed in this model and compared to that of the saline-injected rats. A significant reduction of the escape threshold to mechanical stimulation of the lateral face on the ipsilateral side to the CFA injection was observed at 1–6 days after CFA injection as compared to that of the pre-CFA control (P<0.01). The lateral face region contralateral to the CFA injection also showed mechanical hyperalgesia at 1–6 days after injection (P<0.05). The plasma extravasation was significantly increased in the parotid gland ipsilateral to CFA injection as compared to that of the parotid gland with saline injection at 3 days after injection as shown by Evans' blue dye extravasation (P<0.05). Bilateral expression of Fos protein-like immunoreactive cells was observed in the transition zone between the trigeminal spinal nucleus interpolaris (Vi) and caudalis (Vc) and paratrigeminal nucleus (Pa5). On the other hand, a significant unilateral expression of Fos protein-positive cells was observed on the ipsilateral side of the upper cervical (C2) dorsal horn (P<0.05). This model of parotitis can be used to study trigeminal pain mechanisms associated with sialadenitis. A unique feature of this preparation is that the inflammation was limited to the parotid gland after intraductal injection of CFA, allowing analysis of peripheral input from a defined orofacial region. The model will be useful in developing new strategies to treat chronic orofacial pain.Abbreviations NTS Nucleus tractus solitarius - ECu External cuneate nucleus - CFA Complete Freund's adjuvant - Cu Cuneate nucleus - Gr Gracile nucleus - IO Inferior olivary nucleus - LI Like-immunoreactivity - mlf Medial longitudinal fasciculus - Pa5 Paratrigeminal nucleus - PBS Phosphate-buffered saline - PG Parotid gland - Py Pyramidal tract - RVL Rostroventrolateral reticular nucleus - sol Solitary tract - sp5 Spinal trigeminal tract - Vi Subnucleus interpolaris of the spinal trigeminal nucleus - Vc Subnucleus caudalis of the spinal trigeminal nucleus - TB Tris buffer - TMJ Temporomandibular joint - Vi/Vc Trigeminal subnucleus interpolaris/subnucleus caudalis     

E-cadherin and cytokeratin subtype profiling in effusion cytology

Diagnostic utility of E-cadherin (E-CD) and cytokeratin (CK) subtype profiling in effusion cytology was investigated, employing immunocytochemistry on cellblock sections available from 211 metastatic carcinomas (MC), 6 mesotheliomas and 73 reactive mesothelial hyperplasias (MH). E-CD and monoclonal carcinoembryonic antigen (mCEA) stained 85% (120/141) and 65% (138/211) of MC, respectively. E-CD staining of MC was frequently heterogeneous (76/120) and absent in all anaplastic carcinomas (0/2). E-CD stained none (0/57) of MH while mCEA and epithelial membrane antigen (EMA) stained 12% (9/73) and 32% (16/32) of MH, respectively. Of 6 mesotheliomas, E-CD focally stained in 2 while mCEA stained none and EMA stained all. CK20 and CK17 stained none of MH or mesotheliomas. CK20 stained 15% of MC and CK 17 stained 22% of MC. CK5/6 and high molecular weight CK stained all mesotheliomas, 56% and 88% of MH, 26% and 39% of MC, respectively. MC showed predominant CK7+/20-expression, with the exceptions of MC from mucinous type of colon/rectum and ovary showing predominant CK20 positive. E-CD may be a useful positive marker for MC in effusion cytology, although it may focally stain in some mesotheliomas. Any positive staining for CK20 of MC suggests MC from the gastrointestinal tract or ovary among others.     

Differential Diagnosis of Solitary Pulmonary Inflammatory Lesions and Peripheral Lung Cancers with Contrast-enhanced Computed Tomography

OBJECTIVES:To clarify differences between solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomography.METHODS:In total, 64 and 132 patients with solitary pulmonary inflammatory masses/nodules and peripheral lung cancers, respectively, were enrolled in this study. Their computed tomographic findings were summarized and compared retrospectively.RESULTS:Compared with the peripheral lung cancers, the inflammatory lesions were located closer to the pleura (p<0.0001). The majority of the inflammatory lesions were patchy and oval-shaped (82.8%), whereas most of the tumors were lobulated (82.6%). Almost all the inflammatory cases were unclear (93.8%), whereas most of the tumors had spiculated margins (72.7%). Computed tomography values were significantly higher for the inflammatory lesions than for the cancers (p<0.0001). More than half of the inflammatory lesions had defined necrosis (59.3%). Furthermore, 49.2% of the cancers enhanced inhomogeneously, but only 24.6% had ill-defined necrosis or cavities. The peripheral zones of 98.4% of the inflammatory lesions and 72.7% of the tumors were unclear, with peripheral scattered patches (92.2%) and beam-shaped opacity (66.7%) being the most common findings, respectively. Adjacent pleural thickening was more frequent for the inflammatory lesions than the cancers (95.3% vs. 21.1%, p<0.0001), whereas pleural indentation was found in 67.4% of the subjects with cancer. In addition, hilar (p=0.034) and mediastinal (p=0.003) lymphadenopathy were more commonly detected in the cancers than in the inflammatory cases.CONCLUSIONS:Contrast-enhanced computed tomography findings for pulmonary inflammatory lesions and peripheral lung cancers were significantly different in many aspects. Developing a comprehensive understanding of these differences is helpful for directing their management.