Chylothorax and constrictive pericarditis in a woman due to generalized lymphatic anomaly: a case report.

BACKGROUND: Generalized lymphatic anomaly (GLA) is characterized by diffuse or multicentric proliferation of dilated lymphatic vessels resembling common lymphatic malformations. Compared with soft tissue or bone involvement, thoracic involvement may be associated with a worse prognosis. CASE PRESENTATION: We reported a case of GLA with chylothorax and constrictive pericarditis in a 29-year-old woman. This patient exhibited remarkable features, including a continuously hemorrhagic chylothorax, constrictive pericarditis, and involvement of bone and neck lymph nodes. After attempting to manage her condition with conservative treatment, the patient underwent pericardial stripping surgery. Exploration revealed abundant hyperplasia of tubular tissue in the aortopulmonary window in both pleural cavities. CONCLUSIONS: This case highlights the importance of maintaining the clinical suspicion of GLA during the follow-up of chylothorax patients. Aggressive pericardial surgery, which is important for both diagnosis and treatment, should be performed in patients with GLA with constrictive pericarditis.

A case report of heterozygous TINF2 gene mutation associated with pulmonary fibrosis in a patient with dyskeratosis congenita.

RATIONALE: Dyskeratosis congenita (DC) is a rare inherited disease characterized by the classical mucocutaneous triad. Pulmonary fibrosis, bone marrow failure, and solid tumors are the main causes of mortality in DC. Pathogenic variants in TERT, TERC, and DKC1 have been identified in individuals with familial pulmonary fibrosis. Mutations in TINF2 gene have been reported to be associated with bone marrow failure in most cases. However, the relationship between TINF2 mutation and pulmonary fibrosis is not yet clear. PATIENT CONCERNS: Here, we report the case of a 32-year-old woman presented with irritating cough for 2 years and progressive breathlessness for 6 months. DIAGNOSES: The patient was diagnosed with DC based on the following clinical evidences. Along with some family members, she had the typical mucocutaneous triad and pulmonary fibrosis. A heterozygous mutation (c.844C>T), located in exon 6 of TINF2 gene, that changed arginine to cysteine (Arg282Cys) was identified in this proband by whole exome sequencing. INTERVENTIONS: The patient received corticosteroid therapy but refused to receive lung transplantation. OUTCOMES: The proband died of respiratory failure 4 months after the diagnosis. The missense mutation was located in the conserved region of TINF2 gene and predicted to be deleterious by altering the protein structure. LESSONS: Lung transplantation should be considered for improved survival of patients with DC, and pulmonary fibrosis. Whole exome and whole genome sequencing should be widely used in the identification of such rare genetic variants for clinical diagnosis. The study of DC with pulmonary fibrosis can provide a more appropriate means of clinical research and therapy to the unfortunate patients who suffer from this rare disorder.

[Inhibition of the aquaporin-1 gene expression by RNA interference: experiment with cultured rat pleural mesothelial cells].

OBJECTIVE: To investigate the influence of RNA interference (RNAi) on the expression of aquaporin-1 (AQP1) gene and to investigate the feasibility of gene therapy for pleural effusion. METHODS: Two recombinant plasmids with shRNAs targeting the AQP1 gene, AQP1-1-pGenesil and AQP1-2-pGenesil-1 were constructed. Pleural mesothelial cells were obtained from rats, cultured, and randomly divided into 5 groups: blank control group, Lipofectamine 2000 control group, HK negative control group, AQP1-1-pGenesil-1 transfected group, and AQP1-2-pGenesil-1 transfected group. RT-PCR and Western blotting were used to detect the mRNA and protein expression of AQP1. RESULTS: The mRNA expression levels of aquaporin-1 of the AQP1-1-pGenesil-1 and AQP1-2-pGenesil-1 transfected groups were inhibited by 83.5% and 90.9% respectively, and the protein expression levels of the AQP1-1-pGenesil-1 and AQP1-2-pGenesil-1 transfected groups were inhibited by 41.2% and 67.6% respectively. CONCLUSION: RNAi can successfully inhibit the expression of AQP1 and has the feature of sequence correlation of shRNA in the cultured rat pleural mesothelial cells. It may be used as a potential new approach for gene therapy of pleural effusion.

Increased expression of aquaporin-1 on the pleura of rats with a tuberculous pleural effusion.

OBJECTIVE: The purpose of this study was to investigate whether the expression of AQP-1 on the pleura is altered in a rat model with a tuberculous pleural effusion (TPE) and to study its function. METHODS: A TPE model was established by intrapleural inoculation with 0.03 mg (2 ml) standard tuberculosis bacillus (H(37)Rv). The rats with TPE were sacrificed at different time points (day 1, 3, or 5) after inoculation. The control group received a 2-ml intrapleural injection of saline. The visceral and parietal pleural tissues were harvested and processed for real-time RT-PCR, Western blot, immunohistochemistry, and determination of tissue AQP-1 levels. Recombinant adenovirus Ad-rAQP-1 containing full-length cDNA of AQP-1 was constructed. Six groups of seven Wistar rats were assigned to receive the following treatments: group 1: intrapleural administration of normal saline; group 2: intrapleural administration of tuberculosis bacilli (TB); group 3: intrapleural inoculation with TB at day 7 following intrapleural administration of Ad-rAQP-1 vector; group 4: intrapleural inoculation with 0.03 mg TB at day 7 following intrapleural administration of control Ad-GFP vector; group 5: intrapleural administration of Ad-rAQP-1; group 6: intrapleural administration of control Ad-GFP vector. The expression of AQP-l on the pleural tissue was detected by immunohistochemistry and Western blot analysis. Histopathologic changes of the pleura and the volume of pleural fluid were examined on day 7 following gene intervention or on day 3 following TB inoculation. RESULTS: Bilateral pleural effusions appeared within 5 days in all rats who received an intrapleural inoculation with TB. The peak amount of pleural fluid occurred on day 3. The AQP-1 expression at protein and mRNA was increased in the early phase of TPE. The expression of AQP-1 was increased in the Ad-rAQP-1 gene transfer group, indicating successful adenovirus gene transfer. The volume of pleural fluid in group 3 (6.1 +/- 0.7 ml) was significantly increased compared with that in group 2 (3.8 +/- 1.0 ml) and group 4 (4.0 +/- 1.1 ml). CONCLUSION: These findings suggested that AQP-1 was increased in TPE and it may be involved in the formation of TPE.