Pleural Compartment Research Articles

Syringopleural shunt for refractory syringomyelia: how I do it.

Surgical treatment of syringomyelia is directed at the reconstruction of the subarachnoid space and restoration normal cerebrospinal fluid flow. Direct intervention on the syrinx is a rescue procedure and should be offered to patients with refractory syringomyelia. We provide an overview on indications and technique of syringopleural shunt (SPS). The procedure involves the connection of syrinx with the pleural space using a lumboperitoneal shunt. The occurrence of a negative pressure inside the pleural compartment offers an appropriate gradient for drainage from the syrinx. The SPS allows for a safe and effective treatment of persistent syringomyelia when management of the underlying cause does not yield substantial improvement.

Characterizing Outcomes in Visceral Cutaneous T-Cell Lymphoma: A Real-World Retrospective Study

Introduction: Visceral Cutaneous T-Cell Lymphoma (vCTCL) is a rare and understudied complication of CTCL. Visceral involvement is associated with a poor prognosis, with a median survival of less than 1.5 years. We aimed to assess clinical characteristics, treatment, and outcomes associated with vCTCL. Methods: We conducted a retrospective review of patients with vCTCL from a CTCL database of 656 patients seen at the Winship Cancer Institute at Emory University from 1990-2022. vCTCL was defined as stage 4B or M1 disease that was pathologically confirmed or clinically suspected. Clinical data collected from the electronic medical record included baseline demographics, disease characteristics, pathologic characteristics, laboratory values, and treatment patterns. Descriptive analysis was performed for covariates. Clinical outcomes were measured as overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method and univariable Cox regression analysis. Statistical analysis was performed using SAS with significance at the 0.05 level. Results: Twenty-six patients had vCTCL of which 42.3% were black and 57.7% were white. There was an even distribution among male (53.8%) and female patients (46.2%) [Table 1]. Median age at diagnosis of vCTCL was 58.5 years (47-66). Eight patients (30.8%) had ECOG PS ≥2. The most common diagnosis was mycosis fungoides (73.1%) and Sézary syndrome (11.5%), others being primary cutaneous anaplastic large cell (n=1), cytotoxic T cell (n=1), and gamma-delta T cell lymphoma variants (n=1). At the time of initial diagnosis, TNMB stage was 1B in 7 patients (33.3%), 2A/2B in 6 (28.6%), 3A in 2 (9.5%), 4A1/A2 in 4 (19%), and 4B in 7 (33.3%). Four patients (15.4%) had N2 involvement and 8 patients (30.8%) had N3 involvement. Eight patients had stage B2 disease (30.8%). Approximately half of the cohort had large cell transformation (LCT) with 61.5% having concurrent biopsy-proven LCT with visceral metastasis. Eleven patients (60%) had matched skin and blood TCR positivity. Twenty-three patients had biopsy-proven vCTCL with the most common sites being lung (42.3%), liver (19.2%), bone marrow (11.5%), and CNS (11.5%). Nine patients (34.6%) had at least 2 sites of metastases. Liver metastases were associated with a higher rate of subsequent disease progression (HR 3.29, p=0.031). Other metastases (23%) involving the thyroid, kidney, pleural or peritoneal compartments were associated with decreased survival (HR 8.91, p<0.001) and progression (HR 4.28, p=0.009). Median follow-up was 28.4 months (mo). The median time to visceral involvement from diagnosis was approximately 1 year. Nearly all patients (96.2%) received treatments after vCTCL diagnosis. Median time to first treatment of vCTCL was 2.3mo. Median number of systemic therapies after vCTCL diagnosis was 2. Two patients had complete response (7.7%) and one had partial response (3.8%) with the rest having progressive disease (88.5%). There was no difference in OS or PFS by race, and black patients had a trend toward improved outcomes. Median OS in black and white patients was 18.2mo and 11.4mo respectively (HR 0.5, p = 0.097, Figure 1). Median PFS in black and white patients was 8.7mo and 4.3mo respectively. Black patients had higher median lactate dehydrogenase levels at vCTCL diagnosis (p=0.018) and trended towards an earlier age at diagnosis (54 years vs 62 years) and a shorter time to metastasis (7.9mo vs. 13.3mo) but these factors were not associated with survival outcomes. Most patients received multi-agent chemotherapy (n=13), total electron beam therapy (n=11), and brentuximab vedotin (n=6). Black and white patients had similar time to first treatment and total number of treatments. White patients were more likely to receive combination chemotherapy (66.7% vs 27.3%, p=0.047). Two patients in our cohort had durable complete response to therapy. The first patient developed CNS metastases and achieved durable response with HD-MTX. The second patient had concurrent pulmonary vCTCL and LCT and developed durable response with allogeneic transplantation. Treatments, other demographic information, ECOG, histopathology, LCT were not associated with survival outcomes. Conclusions: Our analysis of a large CTCL cohort from a 30-year period confirms the rarity and poor outcomes in patients with visceral CTCL disease. More prospective studies and clinical trials are needed to guide treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Kaposiform Lymphangiomatosis: Pathologic Aspects in 43 Patients.

Kaposiform lymphangiomatosis is an uncommon generalized lymphatic anomaly with distinctive clinical, radiologic, histopathologic, and molecular findings. Herein, we document the pathology in 43 patients evaluated by the Boston Children's Hospital Vascular Anomalies Center from 1999 to 2020. The most frequent presentations were respiratory difficulty, hemostatic abnormalities, and a soft tissue mass. Imaging commonly revealed involvement of some combination of mediastinal, pulmonary, pleural, and pericardial compartments and most often included spleen and skeleton. Histopathology was characterized by dilated, redundant, and abnormally configured lymphatic channels typically accompanied by dispersed clusters of variably canalized, and often hemosiderotic, spindled lymphatic endothelial cells that were immunopositive for D2-40, PROX1, and CD31. An activating lesional NRAS variant was documented in 9 of 10 patients. The clinical course was typically aggressive, marked by hemorrhage, thrombocytopenia, diminished fibrinogen levels, and a mortality rate of 21%.

LONGLINES IN NEONATAL PRACTICE – ITS EMERGING NEED IN SPECIAL NEWBORN CARE UNIT

Background: Longlines are commonly used in neonatal practice in the West. Its correct placement is important to avoid complications such as extravasation of fluids into pleural, pericardial, and subcutaneous compartments which may prove fatal in some neonates. Objective: The objective of the study was to review the indications, insertion characteristics, post-insertion care, and complications of longlines in sick neonates and to emphasize its use in managing extremely low birth weight (ELBW) and very low birth weight (VLBW) babies at special newborn care unit (SNCU) level. Materials and Methods: A prospective cross-sectional observational study of all longline insertions during January 2014–June 2019 in the SNCU of a medical college of the Eastern State was undertaken. The indications, number of attempts at insertion, procedure time, and duration of longline stay, number of dressing change, complications and cause of removal were noted and the study variables were analyzed. Results: A total of 312 neonates were included; of them, 140 were ELBW and 172 were VLBW babies. Successful insertion of longlines in the first attempt occurred in 294 (94.23%) neonates. 16 (5.12%) neonates required second attempt, while only 2 (0.64%) required third attempt. The average time taken for the procedure was 30 min–1 h and average duration of longline stay was 18.3 days. Low complication rates were recorded such as occlusion in 24 (7.69%) cases, dislodgement in 3 (0.96%), migration in 4 (1.28%), sepsis in 15 (4.8%), and profuse bleeding at insertion site in 1 (0.32%) neonates. Conclusion: Longline is a safe, effective, and reliable method of providing prolonged IV access in sick small neonates, especially ELBW and VLBW babies. Longlines can be recommended for routine use at SNCU level.

Bilateral chylothorax as a complication of internal jugular vein cannulation.

Sir, We thank the reader for the interest shown and an incisive analysis of our article.[1] We would like to clarify the queries raised as follows:- The mechanism of bilateral chylothorax after thoracic duct injury is not clearly known but has been hypothesized based on the various case reports that have been described in the past and in our article. Paw described a case of bilateral pleural effusion as a complication of left internal jugular venous catheterization for total parenteral nutrition.[2] The author had suggested that the tip of the catheter might have migrated into the mediastinum and that fluid from the mediastinum had entered both the pleural spaces via anatomical communications, which have not yet been described. Similar instances where contralateral or bilateral effusions have occurred after central line insertion have been reported.[34567] Varache attributed it to a possible mediastinal pleural ruture.[7] Naquib et al. have ascribed the phenomenon to the pressure difference between the mediastinal compartment and the pleural compartments, which leads to the extravasation of fluid from the mediastinum to bilateral pleural spaces. They also demonstrated the same with instillation of a radio-opaque dye through the central line and its appearance in the mediastinum[4]As described in our article, after the inadvertent injury to thoracic duct, during central venous cannulation, the chyle first leaks out either into the ipsilateral pleural space through a pleural breach that occurred during cannulation (which would explain the development of unilateral chylothorax), or the chyle could extravasate into the mediastinal compartment. From there, after a latent period of about two days, the chyle enters one or both pleural spaces because of the pressure difference between the compartments. This would explain the instances of the contralateral and bilateral chylothoraces. The authors agree with the various mechanisms proposed by the reader except that occlusion or near occlusion of the thoracic duct (post-injury) were unlikely in our case considering the early and complete resolution that occurred. All the other stated mechanisms were plausible.During our literature search we found five case reports where the mechanism of chylothorax was a direct injury to thoracic duct or lymphatic vessels. We had listed the same in our article and as shown in the table, all had either ipsilateral or bilateral chylothoraces. Contralateral chylothoraces have been described in those cases where the central venous cannulation had led to thrombosis of central veins. The extension of thrombi and back pressure effects may lead to ipsilateral, contralateral or bilateral chylothorax The origin of the swelling in the supraclavicular fossa has not been conclusively determined, but has been observed in other reports too. Most experts believe that when the duct starts to leak, a mediastinal chyloma is first formed below the pleura which tracks up to appear above the sibson's fascia and causes the supraclavicular swelling. The same mediastinal chyloma may enter the pleural space to cause chylothorax.[8910] However, as mentioned earlier, the mechanism has not been conclusively elucidated. We thank the reader again for bringing out these important anatomical considerations which are intuitively unclear and may require experimental studies for understanding the mechanism more explicitly.

Pharmacokinetics of Linezolid and Ertapenem in experimental parapneumonic pleural effusion

ObjectiveTo determine the extent of linezolid and ertapenem penetration into the empyemic fluid using a rabbit model of empyema.MethodsAn empyema was created via the intrapleural injection of Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracocentesis, 24 hours post inoculation, linezolid (10 mg/kg) and ertapenem (60 mg/kg) were administered intravenously into 10 and 8 infected empyemic rabbits, respectively. Antibiotic levels were determined in samples of pleural fluid and blood serum, collected serially at 1, 2, 4, 6 and 8 hours, after administration each of the two antibiotics.ResultsLinezolid as well as ertapenem penetrate well into the empyemic pleural fluid, exhibiting a slower onset and decline compared to the corresponding blood serum levels. Equilibration between blood serum and pleural fluid compartments seems to occur at 1.5 hours for both linezolid and ertapenem, with peak pleural fluid levels (Cmaxpf of 2.02 ± 0.73 «mu»g/ml and Cmaxpf of 3.74 ± 1.39 «mu»g/ml, correspondingly) occurring 2 hours post antibiotics administration and decreasing very slowly thereafter. The serum concentrations for both antibiotics were significantly lower from the corresponding pleural fluid ones during the 8 hours collecting data, with the exception of samples collected at the 1st hour (Cmaxserum of 2.1 ± 1.2 «mu»g/ml for linezolid and Cmaxserum of 6.26 ± 2.98 «mu»g/ml for ertapenem).ConclusionPleural fluid levels of both antibiotics are inhibitory for common specified pathogens causing empyema.

Pleural Mesothelial Cells Express Both BLT2 and PPARα and Mount an Integrated Response to Pleural Leukotriene B4

Leukotriene B(4) (LTB(4)) plays a crucial role in the recruitment of neutrophils into the pleural space. We identified for the first time the mechanisms by which LTB(4) interacts with mesothelial cells and recruits neutrophils in the pleural compartment. Primary pleural mesothelial cells express both the proinflammatory receptor for LTB(4) BLT2, and the anti-inflammatory receptor for LTB(4), PPARalpha. Parapneumonic pleural effusions highly increase BLT2 expression and, via BLT2 activation, increase the adhesion between mesothelial cells and neutrophils and the expression of ICAM-1 on mesothelial cells. The block of PPARalpha further increases both cell adhesion and ICAM-1 expression. BLT2 activation promotes the activation, on mesothelial cells, of STAT-1 but not the activation of NF-kappaB transcription factor. The increase of ICAM-1 expression is achieved via increased tyrosine phosphorylation activity since herbimycin, a tyrosine kinase inhibitor, reduces and since Na orthovanadate, a tyrosine phosphatase inhibitor, further increases ICAM-1 expression. This study demonstrates that pleural mesothelial cells, expressing both proinflammatory and anti-inflammatory LTB(4) receptors, are able to mount an integrated response to LTB(4) with a prevalence of BLT2 activities in the presence of an inflammatory milieu within the pleura.

The pathogenesis of pleural space loculation and fibrosis

Organization of parapneumonic effusions may complicate pneumonia, and, annually, thousands of patients require procedures to treat intrapleural loculation and fibrosis. Surgical procedures are often used for the treatment, as fibrinolytic therapy is now not a routine and is undergoing reassessment. Investigation of mechanisms that underlie intrapleural loculation and fibrosis is therefore timely, as are studies on new strategies to medically address these problems with improved efficacy and safety. Contributions made over the past year include basic and translational studies unified by their broad focus on mechanisms by which the pleural compartment undergoes repair. Intrapleural single-chain urokinase was reported to effectively reverse intrapleural loculation when compared with commercially available agents in rabbits with tetracycline-induced pleurodesis. The ability of exogenous sclerosants to produce intrapleural loculation and fibrosis was compared. Overexpression of transforming growth factor beta in the pleural mesothelium promoted subpleural fibrosis, implicating the mesothelial cell in the pathogenesis of this lesion. A new model of pleurodesis in mice was reported, which could facilitate the use of transgenic animals to study the pathogenesis of pleural injury. New findings consolidate and extend the view that common mechanisms by which intrapleural organization occurs can be exploited to either generate pleurodesis or effectively reverse intrapleural loculation and fibrosis.

Alcohol Binge Before Trauma/Hemorrhage Impairs Integrity of Host Defense Mechanisms During Recovery

Alcohol abuse, both chronic and acute, is a known modulator of immune function and is associated with increased incidence of traumatic injury. Previously, we demonstrated that acute alcohol intoxication before hemorrhagic shock impairs hemodynamic and neuroendocrine counterregulation, suppresses early lung proinflammatory cytokine expression, and increases mortality from infection during recovery. In the present study, we examined the impact of a 3-day alcohol binge on host responses during trauma/hemorrhage (T x Hem) and following overnight recovery. Chronically catheterized, adult male Sprague-Dawley rats were administered an intragastric bolus of alcohol (5 g/kg; 30% w/v) or isocaloric dextrose solution for 3 consecutive days, followed by a 2.5 g/kg dose on day 4 before undergoing full-thickness muscle-crush and fixed pressure (approximately 40 mmHg) hemorrhage and fluid resuscitation (2.4 x total blood volume removed). Alcohol-binge produced a 16% decrease in basal mean arterial blood pressure (MABP), reduced the total blood loss required to reach and to sustain MABP of 40 mmHg, markedly blunted the increase in circulating epinephrine and norepinephrine (20-fold and 3-fold, respectively) levels, and increased immediate mortality from T x Hem. Consistent with our previous reports, significant up-regulation in lung and spleen tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha expression was observed immediately following T x Hem and fluid resuscitation. Only the T x Hem-induced increase in lung TNF-alpha was prevented by binge alcohol administration. Following overnight recovery, significant lipopolysaccharide (LPS)-stimulated release of TNF-alpha, IL-1alpha, IL-6, and IL-10 was observed in cells isolated from blood and the alveolar and pleural compartments from all experimental groups. While T x Hem did not prevent LPS-induced release of TNF-alpha, IL-1alpha, IL-6, or IL-10 at 6 or 24 hours, alcohol binge suppressed TNF-alpha, IL-1 and IL-6 release, without altering IL-10 response in cells isolated from blood and pleural compartment. No significant modulation of alveolar macrophage response was observed following alcohol binge and T x Hem. These results indicate that a 3-day alcohol binge results in hemodynamic instability associated with attenuated neuroendocrine activation and increased mortality during T x Hem as well as sustained suppression of the proinflammatory cytokine response of blood and pleural-derived cells to a "second-hit" inflammatory challenge. As a result, we speculate that the net shift toward an anti-inflammatory state may contribute to enhanced susceptibility to infection during the recovery period.

Thrombin–thrombomodulin inhibits prourokinase-mediated pleural mesothelial cell-dependent fibrinolysis

Fibrin deposition is a hallmark of pleural inflammation and loculation but understanding of mechanisms by which mesothelial cells regulate intrapleural fibrinolysins remains incomplete. We speculated that pleural mesothelial cells regulate local fibrinolytic capacity via processing of single chain urokinase type plasminogen activator (scuPA). Pretreatment of human pleural mesothelial (MeT-5A) cells with TGF-β or thrombin, either alone or in combination, inhibited urokinase (uPA)-mediated fibrinolysis by MeT-5A. Thrombin, unlike TGF-β, inhibited fibrinolysis without induction of PAI-1, suggesting that thrombin-mediated cleavage of scuPA inhibits the fibrinolytic capacity of MeT-5A cells. Thrombin cleaves both purified scuPA as well as that secreted by MeT-5A cells and cell surface thrombomodulin accelerates thrombin-mediated cleavage of scuPA to inhibit cellular fibrinolytic activity. Molecular dynamics analyses demonstrated that thrombin-cleaved scuPA (uPAt) do not acquire a catalytically active conformation and that secondary plasminogen binding sites of uPA implicated in plasminogen activation are distorted in uPAt, explaining, at least in part, why uPAt is a poor enzyme. uPAt was detectable in transudative and exudative pleural effusions from patients. Intrapleural administration of scuPA generated increased levels of uPAt in PF of rabbits with pleural injury and loculation induced by tetracycline in vivo. This pathway is operative in diverse forms of pleural injury, restricts the urokinase-dependent fibrinolytic capacity of pleural mesothelial cells and contributes to local control of fibrinolytic activity via processing of endogenous or exogenous scuPA within the pleural compartment.

Matrix-Metalloproteinasen und deren Inhibitoren bei Lungenkarzinomen mit malignem Pleuraerguss

Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) play a crucial role in physiological and pathological matrix turnover. This study aimed to determine the occurrence of MMP and TIMP in lung cancer patients with malignant pleural effusions (CA). MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1, and IMP-2 oncentrations were determined by ELISA and zymography in pleural effusions and plasma of 31 CA and 14 congestive heart failure (CHF) patients and in plasma of 18 healthy controls (CON). MMP-2, TIMP-1, and TIMP-2 ELISA-concentrations were increased in CA pleural fluid vs. CA plasma (p < 0.005, p < 0.005, p < 0.05), in contrast to MMP-9 being higher in plasma (p < 0.005). Pleural fluid MMP-1 and MMP-8 were increased in CA vs. CHF (p < 0.05, p < 0.005). MMP and TIMP plasma concentrations were not different in CA vs. CHF, but MMP-9, TIMP-1, and TIMP-2 were increased vs. CON (p < 0.005, each). Gelatine zymography MMP-9/MMP-2 ratios were increased in CA plasma vs. effusion fluid (p < 0.005), in CA vs. CHF plasma, CA vs. CHF effusions (p < 0.005 each), and in CA vs. CON plasma (p < 0.05). MMP-2, TIMP-1, and TIMP-2 accumulate in the pleural compartment in CA and CHF, probably reflecting an unspecific pleural reaction. MMP-1 and MMP-8 are increased in cellular rich CA pleural effusions only. The determination of MMP-9/MMP-2 ratios in pleural fluid may contribute to differentiate CHF from CA effusions.

Erschwerter Verlauf von Ösophagusperforationen durch Pilzinfektion

ZusammenfassungDie Ösophagusperforation hat eine hohe Letalitätsrate, welche zwischen 7 und 49% schwankt. Im untersuchten Kollektiv aus den Jahren 1986 bis 2003 war die hohe Letalitätsrate von 28% vorwiegend durch septische Komplikationen wie Mediastinitiden und Pneumonien verursacht. In den mikrobiologischen Untersuchungen unterschiedlicher Lokalisationen und Sekrete wurden bei 28% der Patienten (n = 16) Pilze nachgewiesen. Im Vergleich zum Gesamtkollektiv führte der Pilzbefall zu einer erhöhten Letalität um 50%. Die invasive ösophageale Candidose kann ihrerseits Ursache einer Ösophagusperforation sein. Begleitende Pilzinfektionen entstehen bei Ösophagusperforationen durch das Einbrechen der Perforation in sterile Kompartimente oder durch hämatogene und lymphogene Ausbreitung bis hin zur Sepsis. Bei unkompliziertem Krankheitsverlauf ist eine antimykotische Therapie nicht erforderlich. Vom Anfang der Behandlung an sollte ein mikrobiologisches Monitoring erfolgen, insbesondere des intraoperativen Befundes. Je nach Risikofaktoren und klinischem Verlauf der Patienten muss mit einer antimykotischen Therapie reagiert werden. Besondere Bedeutung kommt einer chirurgischen Sanierung und einer suffizienten Drainage der beteiligten Kompartimente wie Pleura und Mediastinum zu.

Biologically active intercellular adhesion molecule-1 is shed as dimers by a regulated mechanism in the inflamed pleural space.

Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that plays a crucial role in cell-cell interactions involved in the recruitment of cells and immune responses. Under some circumstances, ICAM-1 is found as a soluble protein that has the potential to influence the nature of immunoinflammatory responses. By examining cells and fluid from the pleural compartment of patients with cancer, tuberculosis, and congestive heart failure, the cellular source, conformation, control, and biological activity of soluble ICAM-1 (sICAM-1) were investigated. The results suggest that dimeric sICAM-1 was released locally in the pleural compartment of tuberculous and malignant effusions. sICAM-1 was shed from preexpressed surface ICAM-1 rather than produced de novo, and both CD45-positive leukocytes and cytokeratin-positive epithelial and mesothelial cells expressed ICAM-1, suggesting multiple cellular sources for sICAM-1. The expression of sICAM-1 was regulated because pleural macrophages caused release of sICAM-1 via a tumor necrosis factor-alpha-dependent mechanism. The functional significance of sICAM-1 was demonstrated by showing that pleural sICAM-1 interfered with conjugate formation between LAK cells and K562 cells, suggesting that pleural sICAM-1 plays an immunosuppressive role by inhibiting adhesion of cytotoxic lymphocytes and tumor cells. Thus, sICAM-1 is shed from the surface of cells in a regulated manner and has the potential to influence the immune response in the pleural space.

Role of aquaporin water channels in pleural fluid dynamics.

Continuous movement of fluid into and out of the pleural compartment occurs in normal chest physiology and in pathophysiological conditions associated with pleural effusions. RT-PCR screening and immunostaining revealed expression of water channel aquaporin-1 (AQP1) in microvascular endothelia near the visceral and parietal pleura and in mesothelial cells in visceral pleura. Comparative physiological measurements were done on wild-type vs. AQP1 null mice. Osmotically driven water transport was measured in anesthetized, mechanically ventilated mice from the kinetics of pleural fluid osmolality after instillation of 0.25 ml of hypertonic or hypotonic fluid into the pleural space. Osmotic equilibration of pleural fluid was rapid in wild-type mice (50% equilibration in <2 min) and remarkably slowed by greater than fourfold in AQP1 null mice. Small amounts of AQP3 transcript were also detected in pleura by RT-PCR, but osmotic water transport was not decreased in AQP3 null mice. In spontaneously breathing mice, the clearance of isosmolar saline instilled in the pleural space ( approximately 4 ml. kg(-1). h(-1)) was not affected by AQP1 deletion. In a fluid overload model produced by intraperitoneal saline administration and renal artery ligation, the accumulation of pleural fluid (approximately 0.035 ml/h) and was not affected by AQP1 deletion. Finally, in a thiourea toxicity model of acute endothelial injury causing pleural effusions and lung interstitial edema, pleural fluid accumulation in the first 3 h ( approximately 4 ml. kg(-1). h(-1)) was not affected by AQP1 deletion. These results indicate rapid osmotic equilibration across the pleural surface that is facilitated by AQP1 water channels. However, AQP1 does not appear to play a role in clinically relevant mechanisms of pleural fluid accumulation or clearance.

Induction of acute pleural inflammation by Staphylococcus aureus. I. CD4+ T cells play a critical role in experimental empyema.

Bacterial empyema is a frequent complication of pneumonia in patients with acquired immunodeficiency syndrome (AIDS). A model of Staphylococcus aureus empyema was developed that closely resembles bacterial empyema in patients infected with human immunodeficiency virus (HIV). Results show a compartmentalized chemokine response in bacterial empyema. The chemokine levels were higher in the pleural compartment than in the peripheral circulation. Polymorphonuclear leukocyte counts, murine GRO-alpha (KC), and macrophage inflammatory protein-2 levels were significantly (P<.001) lower in CD4+ knockout (CD4 KO) mice pleural fluid than in CD4+ wild-type (CD4 WT) mice. The CD4 KO mice had poorer bacterial clearance than CD4 WT mice. During S. aureus infection, interleukin-10 levels increased in the CD4 KO mice, whereas interferon-gamma levels were increased in CD4 WT mice. CD4+ T cell depletion results in a decreased pleural chemokine response, decreased neutrophil influx into pleural space, and impaired bacterial clearance in empyema.

Kallikrein–kinin in infection and cancer

This review article describes the mechanism of enhancement of vascular permeability in infectious disease and cancer. This phenomenon is primarily mediated by bradykinin, nitric oxide and other unique vascular mediators. They are highly intermingled with each other in these disease states. Furthermore, these mediators are elicited in various in vivo settings most frequently induced by bacterial proteases, and indirect or direct activation of kallikrein–kinin cascade at one or more steps. The key steps involve bacterial proteases or cellular components including lipopolysaccharides. Thus, the use of appropriate protease inhibitors or antagonists, or scavengers in the case of nitric oxide, superoxide or peroxynitrite, are anticipated to attenuate the clinical manifestation induced by such mediators. It also explained that fluid accumulation in ascitic or pleural compartments in the case of carcinomatosis in terminal cancer patients can be largely attributed to bradykinin or related mechanism. Systemic bacterial dissemination is also facilitated by bradykinin, or suppressed by kinin antagonists as well as by the inhibition of kinin production, respectively. Thus, control of the level of such vascular mediators appears important both in infectious disease and in cancer. α1-Protease inhibitor, which inhibits neutrophil elastase, is inactivated by oxidative metabolites such as superoxide and peroxynitrite, and this effect activates matrix metalloproteinases. This indicates that oxidative stress activates proteolytic potential, and thus accelerates the degenerative process upon infection.

Comparison of pulmonary and pleural responses of rats and hamsters to inhaled refractory ceramic fibers.

The present study was designed to determine whether pleural fiber burdens or subchronic pleural fibroproliferative and inflammatory changes can help explain the marked interspecies differences in pleural fibrosis and mesothelioma that are observed following long-term inhalation of RCF-1 ceramic fibers by rats and hamsters. Fischer 344 rats and Syrian golden hamsters were exposed to RCF-1 for 4 h per day, 5 days per week, for 12 consecutive weeks. Lung and pleural fiber burdens were characterized during and after exposure. For all time points, approximately 67% of fibers associated with lung tissues from both rats and hamsters were longer than 5 microns in length. In comparison, fibers longer than 5 microns recovered from the pleural compartment, following a 12-week exposure and 12 weeks of recovery, accounted for 13% (hamsters) and 4% (rats) of the distribution. In the 12 weeks after the cessation of exposure, the number of fibers longer than 5 microns in length remained constant in the hamster at approximately 150 fibers per cm2 pleura. This was 2 to 3 times the corresponding fiber surface density in the rat. Significant pulmonary and pleural inflammation was detected at all time points and for both species. DNA synthesis by pleural mesothelial cells was quantified by bromodeoxyuridine uptake following 3 days of labeling. Labeling indices were higher in hamsters than in rats, both for RCF-1-exposed and filtered air-control animals and was highest for the parietal surface of the pleura. Significantly greater collagen deposition was measured in the visceral pleura of hamsters 12 weeks post-exposure but was not significantly elevated in rats. These findings demonstrate that subchronic inhalation exposure to RCF-1 induces pleural inflammation, mesothelial-cell turnover, pleural fibrosis, and an accumulation of fibers with a length greater than 5 microns in the hamster. The accumulation of long fibers in the pleural space may contribute to the pathology observed in the hamster following chronic inhalation of RCF-1, whereas the presence of short, thin fibers may play a role in the acute-phase biological response seen in both species.

Quantitation in inflammatory pleural disease to distinguish tuberculous and paramalignant from chronic non-specific pleuritis.

AIM: To determine by morphometry if pleural biopsies with the histopathological diagnosis of "non-specific pleuritis", malignant, and tuberculous disease could be distinguished morphologically from those with truly non-specific disease. METHODS:...

Levels of interleukin-8 in tuberculous pleurisy and the profile of immunocompetent cells in pleural and peripheral compartments

Our study investigated the presence of IL-8 in pleural exudates from tuberculosis patients (TBP) ( n = 13), and evaluated whether it was related with the profile of major immunocompetent cells present in their pleural and peripheral compartments. To allow comparisons, an additional group of patients with parapneumonic pleural effusions (PNE) ( n = 7) was included. Blood peripheral immunophenotypic studies were also carried out in 12 age-matched health controls (Co), and 39 tuberculosis patients classified, according to the extent of pulmonary involvement, into mild ( n = 9), and advanced ( n = 30) cases. Patients were recruited before starting therapy, had HIV negative serology, and showed no age differences among groups (mean ± S.D., 40.7 ± 14.7 years). IL-8 concentrations were measured by an ELISA method while immunophenotypic analysis was performed by using FITC-conjugated monoclonal antibodies reacting against the following cell surface molecules: CD3, CD4, CD8, CD25 (IL-2R + cells), CD19, and CD68. IL-8 was detected in all pleural exudates though levels in the TB patients, 384 ± 110 pg/ml, appeared significantly higher than the PNE group, 185 ± 110 pg/mg, ( P < 0.015, mean ± S.D.). In turn, the former group presented values of pleural CD3 +, CD4 +, and CD25, which were found increased in comparison with PNE patients ( P < 0.01). Unlike the pleural compartment, patients with TBP showed a marked and significant decrease in their circulating levels of cells bearing the CD3, CD4, CD19, CD25, and CD68 phenotypes not only when comparing with Co but also with PNE and mild patients. Differences between the levels of pleural and peripheral T-cells from TBP patients may be the reflection of an important influx of T-lymphocytes from the circulatory system to the pleural cavity, probably linked to the presence of chemotactic factors within the pleural fluid like IL-8.

Pulmonary and Pleural Responses in Fischer 344 Rats Following Short-Term Inhalation of a Synthetic Vitreous Fiber: II. Pathobiologic Responses

The pleura is a target site for toxic effects induced by a variety of fibrous particulates, including both natural mineral and man-made vitreous fibers. We examined selected cytological and biochemical indicators of inflammation in both the pleural compartment and pulmonary parenchyma in F344 rats following inhalation of RCF-1, a kaolin-based ceramic fiber. Male F344 rats were exposed by inhalation to 89 mg/m3(2645 WHO fibers/cc) RCF-1 6 hr/day for 5 consecutive days. In lung parenchyma, cytological and biochemical inflammatory responses occurred rapidly following exposure. In contrast, pleural responses were delayed in onset and of a much smaller magnitude than those observed in lung. At both Day 1 and Day 28 postexposure, increased quantities of lactate dehydrogenase,N-acetyl glucosaminidase, alkaline phosphatase, albumin, and neutrophils were present in bronchoalveolar lavage fluid. These responses were attenuated at the latter time point. No significant responses were detected in pleural lavage fluid until 28 days following exposure, at which time elevated numbers of macrophages and eosinophils, but not neutrophils, were observed. Increased albumin and fibronectin were also observed in PLF at this latter time point. These findings demonstrate that the onset of pleural and pulmonary responses following inhalation of RCF-1 are temporally separated and that pleural injury may increase in severity with time following exposure. The increase in severity of pleural inflammation found in the postexposure period cannot be readily explained by fiber translocation.