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Myelomatous pleural effusion: clinical course and immunologic characterization of the pleural fluid cells.

Multiple myeloma is a disease that infrequently involves nonreticuloendothelial tissues and rarely causes pleural effusion. A 59-year-old woman had pleural effusion as the major manifestation of multiple myeloma. Light microscopy of her pleural fluid with Wright stained preparations showed all cells to be bizarre and often multinucleated plasmacytes. Electron microscopy confirmed these results. Intracellular immunofluorescence revealed IgG-kappa immunoglobulin (Ig) in greater than 90% of these cells. Surface immunofluorescence using anti-Ig sera was seen on less than 5% of the pleural fluid cells. 3H leucine incorporation into Ig in vitro was measured for these cells, and secretory curves were obtained that have the typical secretory kinetics of bone marrow plasmacytes. This demonstrates that such cells are viable and are able to synthesize and release immunoglobulin. Treatment of our patient with prednisone, melphalan, and cyclophosphamide resulted in symptomatic improvement and complete resolution of her pleural effusion. Pleural effusion is an unusual but important complication of multiple myeloma and does not necessarily carry the grave prognosis implied in previous reports.

Female

Exploratory proteomic and metabolomic profiling of pleural effusions identifies histone H4 and alanine as promising complementary markers for pleural tuberculosis.

The diagnosis of pleural tuberculosis (Pl-TB) remains challenging. Histopathological analysis and pathogen detection in pleural biopsies are informative but limited. We investigated differentially expressed proteins and metabolites in pleural effusions from patients with Pl-TB, malignancies, and other pathologies. A proteomic analysis of pooled pleural effusions identified 45 proteins exclusively detected or upregulated in Pl-TB samples, many linked to infectious processes. Conversely, 18 proteins were uniquely found or upregulated in malignant pleural effusions, mainly associated with detoxification and hemostasis. To validate these findings, we employed targeted proteomics in individual samples. Eight proteins were validated: S100-A9, histone H4, insulin-like growth factor-binding protein 2, fibrinogen beta chain, ficolin-3, immunoglobulin heavy constant alpha 1, sulfhydryl oxidase 1, and histidine-rich glycoprotein. Additionally, NMR-based metabolomics identified 13 metabolites with differential abundance between Pl-TB and non-TB samples. Notably, N-acetyl-glycoprotein and the branched-chain amino acids, alanine and lysine differed between groups. Proteomic and metabolomic analyses revealed distinct molecular profiles between Pl-TB and non-TB patients, despite intra-group variability. To address this, we applied classification models. Histone H4 and alanine consistently emerged as discriminative features. Overall, this study provides novel insights into the molecular landscape of Pl-TB. The combined quantification of proteins and metabolites may improve differential diagnosis, although should be further validated in larger, independent cohorts before clinical application.

Humans

[Occurrence of pleural mesothelioma. Chronic fibrosing pleurisy and calcified pleural plaques in Turkey in relation with environmental pollution by mineral fibers (author's transl)].

The incidence of pleural mesothelioma (PM), chronic fibrosing pleurisy (CFP) and calcified pleural plaques (CPP) has been studied in Anatolia (Turkey) in relation with environmental pollution by mineral fibers: 1) In central Anatolia, where asbestos deposits have been described, the frequency of CFP and CPP was in the range 2-25%; several cases of PM have been encountered. 2) One area (Cappadoce) is free of asbestos, but contains another kind of mineral fiber: zeolite. In this area, an outbreak of PM has been described in some villages. Among the 600 inhabitants of Karain, 28 cases of PM occurred for the period January 1975-June 1979.

Air Pollutants

[Technic of pleural drainage (emergency pleural drainage)].

Pleural effusion is still often poorly drained: - incorrect introduction of the drain into the thorax, - ill-chosen position of the drain. Simple drainage, a minima, is considered here, that which requires no broad surgical incision and which, in cases of effusion with compression of the lung, is often a life saving procedure which any doctor should be able to carry out, especially if he deals with emergencies. The surest technique consists of placing a No. 30 drain, using a pleurotomy trocart, type Monod or Coquelet, under local anaesthesia. Introduction of the drain using a forceps after an incision with the scalpel blade is only justified if one has no trocart available. So-called disposable drains, mounted on a pointed bevelled needle prepared in advance, are practical but dangerous. Capillary drainages are methods of second choice. They are often excluded within short delays. The efficacy of the drainage depends on its position.

Anesthesia, Local

The pH of sclerosing agents: a determinant of pleural symphysis.

The rate of success in producing pleural symphysis with intrapleural instillation of sclerosing agents has been variable. Differences in the designs of studies probably account for some of the variability, but the reasons for the remainder are not clear. Since a low pH of the pleural fluid is associated with pleural adhesions and loculations, the pH of the commonly used solutions of sclerosing agents was determined, both in their usual concentrations and when diluted with large quantities of exudative pleural fluid. The buffered solution of tetracycline hydrochloride had the most acidic pH (2.0) and showed little change when diluted by pleural fluid. A 0.5 percent solution of sodium hydroxide had the highest pH (13.0). The remainder of the sclerosing solutions showed a range of pH from 4.3 to 8.7. Experimental and clinical experience suggests that tetracycline consistently has the highest rate of success in producing pleural symphysis. It appears that when proper technique is employed, the pH of the solution of the sclerosing agent is an important determinant of the production of pleural symphysis.

Animals

[Study of simultaneous dosage of carcino-embryonic antigen (C.E.A.) and beta 2-microglobulin in serum and pleural liquid (author's transl)].

Simultaneous dosage of carcino-embryonic antigen and beta 2-microglobulin was studied in serum and pleural liquid. Among the 20 patients with non-neoplasic infections, the carcino-embryonic antigen was not increased in the serum and only once at a border-line level in the pleura. The level of beta 2-microglobulin seems to be related to the number of lymphocytes in the pleural liquid (increase in 45% of the cases compared to 20% in the serum). Among the 31 cancer patients, carcino-embryonic antigen is increased in the serum of 36% of the cases and in the pleura of 48%. In 5 observations, the pleural levels were considerably increased compared with serum levels, suggesting the existence of a pleural metastasis. The beta 2-microglobulin is elevated in only 26% of the cases in the pleural liquid and in 13% in the serum. At the present state of knowledge, it therefore seems unnecessary to continue investigations concerning the beta 2-microglobulin. On the contrary, the pleural dosage of carcinoembryonic antigen could contribute to the diagnosis.

Beta-Globulins

Pleural effusions.

Many different conditions result in the accumulation of pleural fluid. A diagnostic thoracentesis should be performed on all patients with pleural effusion from whom pleural fluid can be easily obtained. Empirically we have found that when the pleural effusion is more than 10 mm thick on the lateral decubitus roentgenogram, pleural fluid is easily obtained. At least 30 cc fluid should be obtained and distributed to the various laboratories as outlined in Table 2. The results of these tests will show whether the fluid is a transudate or an exudate. If the fluid is a transudate, no further diagnostic procedures need be directed towards the pleura. If the fluid is an exudate, the diagnosis will frequently be made by these original tests and therapy for the pleural disease can be instituted. If the diagnosis has not been made, the results of these tests should lead to a rational diagnostic attack.

Amylases

BAP1 Loss in Pleural Mesothelioma Is Associated With Reduced Soluble CCL2 in Patient Effusion, Abrogated CCL2-Mediated Monocyte Recruitment In Vitro.

OBJECTIVES: Pleural mesothelioma is an incurable cancer of the cell layer lining the chest wall and lung. Patients frequently present with pleural effusion, which is often drained for symptom relief and enables minimally invasive sampling of the tumour environment, including immune cells and related soluble factors. Most of the mesothelioma tumours exhibit loss of BRCA1-associated protein 1 (BAP1), a multifunctional tumour suppressor protein. Here, we aim to elucidate the effect of BAP1 loss on the mesothelioma microenvironment through profiling soluble factors within pleural effusion. METHODS: A custom panel of 22 soluble factors was measured by Luminex assay and enzyme-linked immunosorbent assay in an initial cohort of 40 patients with known BAP1 status. Validation was performed by enzyme-linked immunosorbent assay in an independent cohort of 100 cases. Secretion of soluble factors and chemoattraction of monocytes were characterised using a CRISPR-mediated BAP1 deletion model in a mesothelioma and a lung cancer cell line. Immune cell infiltration, estimated by CIBERSORT, was further explored in the Cancer Genome Atlas -MESO cohort. RESULTS: Soluble C-C motif chemokine ligand 2 (CCL2) was approximately 55% to 60% lower in pleural effusion from BAP1-loss cases in both independent cohorts. Deletion of BAP1 reduced CCL2 secretion in vitro and abolished CCL2-mediated chemoattraction of monocytes in both mesothelioma and lung cancer cell lines. In the Cancer Genome Atlas -MESO cohort, BAP1-mutant tumours exhibited a reduction in estimated macrophage content. CONCLUSION: Loss of BAP1 impairs CCL2 secretion into pleural effusions, potentially influencing monocyte recruitment into the tumour microenvironment.

BAP1

Diagnostic significance of pH, lactic acid dehydrogenase, lactate and glucose in pleural fluid.

The pH, lactic acid dehydrogenase, lactate and glucose of pleural fluid simultaneous with serum lactic acid dehydrogenase, blood lactate and glucose were determined in 105 pediatric patients. The patients were classified into groups according to the diagnosis. The pleural fluid of empyema cases was found to have the lowest pH with a mean value of 6.83 (p less than 0.0075). The malignant pleural fluid has a relatively low pH with a mean value of 7.32. The lactic acid dehydrogenase in pleural fluid of empyema cases has the highest mean of 1,470.68 (p less than 0.05). The lactic acid dehydrogenase was found increased in malignancy, tuberculosis and parapneumonic effusion cases. Lactate level was found extremely high in empyema cases with a mean value of 13.68. It was also found extremely high in malignancy, tuberculosis and parapneumonic effusion cases. The glucose level was markedly decreased in empyema cases. There exists correlation of pleural fluid lactate to pH, lactic acid dehydrogenase and glucose, as well as that of pH to lactic acid dehydrogenase.

Child

Systemic lupus erythematosus and DNA antibodies in pleural effusions.

The quantity of antibodies to double-stranded DNA (ds-DNA) in 53 pleural effusions from 48 patients was measured by means of a modified Farr technique. In 10 samples, binding of ds-DNA was greater than 5 mg/l (range 6--14 mg/l), five samples being from patients with systemic lupus erythematosus (SLE), four from patients with lung cancer, and one from a patient with pulmonary tuberculosis. After treatment of pleural effusion samples with DNase, there was a marked increase of ds-DNA binding in the SLE group (n = 5), but none in the lung cancer group (n = 7) or in 4 patients with pleural effusions of various origin. In pleural fluid, demonstration of antibodies to ds-DNA and anti-ds-DNA-ds-DNA complexes, unmasked by DNase, may prove valuable when differentiating clinical conditions with pleural effusions.

Antibodies, Antinuclear

Concentrations of ampicillin in pleural fluid and serum after single and repetitive doses of bacampicillin.

In patients with pleural effusions due to malignant disease, estimations of ampicillin were made on simultaneously obtained samples of blood and pleural fluid: (1) from patients (n=11) after the administration of a single dose of 400 mg of bacampicillin, and (2) from patients undergoing treatment with 800 mg of bacampicillin twice daily (a) during the 12 hours after the first dose (n=10) and (b) during the 7 hours after the third dose (n=9). Bacampicillin gave concentrations in the pleural fluid well above the MIC of common pathogens including H. influenzae. Mean peak levels were 1.2 microgram/ml after the 400 mg dose and 3.8 microgram/ml after the first and third doses of 800 mg. The peak appeared later in the pleural fluid in comparison with serum peak levels. The elimination half life was considerably longer in the pleural fluid.

Ampicillin

Acid-base balance of pleural liquid in dogs.

Acid-base balance and electrolyte concentrations were measured in dogs on small artificial hydrothoraces and in vitro on bicarbonate buffered Ringer solution on serosal and interstitial side of specimens of parietal pleura. Under steady conditions, pleural liquid PCO 2 was similar to and pH higher (delta = 0.022 +/- 0.006 SE) than that in mixed venous blood. Computed pleural liquid [HCO-3] was similar to that in venous plasma and hence less than that set by the Donnan effect, with which Na+ and Cl- approximately complied. In vitro, pH, [Na+], [Cl-], and computed [HCO-3] were significantly lower (delta = 0.030 +/- 0.004; -2.6 +/- 0.5; -1.2 +/- 0.5 and -1.7 +/- 0.2 meq/L, respectively) on the serosal than on interstitial side of pleural specimens, PCO2 being 42 mm Hg on both sides . HCO-3 and Na+ were not distributed according to transpleural potential (-0.4 +/- 0.1 mV on serosal side), suggesting an active transport of Na+ and HCO-3 from pleural liquid to blood. This, however, does not seem to add to the absorption pressure of plasma proteins in setting pleural liquid pressure.

Acid-Base Equilibrium

Antenatal phenotype associated with PAK2 pathogenic variants: bilateral pleural effusion as a warning sign.

Fetal pleural effusions can arise in various contexts with different prognosis. They have been reported in fetuses presenting with hereditary or acquired conditions. One particularly rare genetic disorder, known as Knobloch syndrome, seems to emerge as a potential new cause of fetal pleural effusions, associated with severe outcomes. Knobloch syndrome 1 can be caused by biallelic variants in COL18A1. It is primarily characterized by its ophthalmic features, including severe vitreoretinal degeneration with retinal detachment and macular abnormalities. Neurological defects such as encephalocele and developmental delay, along with skeletal and renal malformations, are also associated with the syndrome. The Knobloch syndrome 2 is caused by monoallelic variants in the kinase domain of PAK2. It is less described and seems to also be associated with cardiac and respiratory damage in addition to the Knobloch syndrome 1 phenotype. PAK2 is a ubiquitous protein with a major implication in regulation and remodeling of the cytoskeleton and numerous other cellular pathways. Knobloch-associated variants seem to cause a loss of the kinase function of the protein. Even if the ophthalmic defects are almost constant, PAK2-associated Knobloch syndrome has slightly different features from Knobloch syndrome 1 in which pulmonary and lymphatic damages are still unseen. In a prenatal trio exome sequencing, we identified a novel de novo PAK2 missense variant, NM_002577.4:c.836 A > C, p.(Gln279Pro), classified as likely pathogenic in a 24 weeks of gestation fetus whose only sign was severe bilateral pleural effusion. From a literature review of patients, we recognize this sign as an important antenatal indicator of Knobloch syndrome 2, as it was the first sign identifiable in 2 out of 5 patients. This adds new evidence for the implication of this gene in fetal pleural effusions, with potentially severe outcomes.

Female