Additional case of minocycline-induced cutaneous polyarteritis nodosa: comment on the article by Culver et al.
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Acne Vulgaris↗
Biomedical subjects
Marianne Kambouchner
Publications and source records attributed to Marianne Kambouchner.
The immune paradox of sarcoidosis and regulatory T cells.
Sarcoidosis is characterized by extensive local inflammation (granuloma, cytokine secretion) associated with anergy (poor response to antigens in vitro and in vivo). We postulated that this paradoxical situation would correspond to a disequilibrium between effector and regulatory T lymphocytes (T reg cells). We show that CD4+CD25(bright)FoxP3+ cells accumulate at the periphery of sarcoid granulomas, in bronchoalveolar lavage fluid, and in peripheral blood of patients with active disease. These cells exhibited powerful antiproliferative activity, yet did not completely inhibit TNF-alpha production. Sarcoidosis is therefore associated with a global T reg cell subset amplification whose activity would be insufficient to control local inflammation. At the same time, peripheral T reg cells exert powerful antiproliferative activity that may account for the state of anergy. Altogether, these findings advance our conceptual understanding of immune regulation in a way that resolves the immune paradox of sarcoidosis and permit us to envisage a profound clinical impact of T reg cell manipulation on immunity.
Adult↗
Carinal replacement with an aortic allograft.
BACKGROUND: Carinal replacement after extensive resection remains a tremendous challenge in thoracic surgery. In previous studies, we demonstrated that an aortic graft could be a valuable tracheal substitute. The goal of this new study was to evaluate the reconstruction of the carina using a stent supported bifurcated aortic allograft. METHODS: In 15 sheep the replacement of the tracheobronchial bifurcation with an aortic allograft was performed under cardiopulmonary bypass. A temporary stent prevented airway collapse. No immunosuppression was used. Aortic segments were retrieved at regular intervals up to 24 months after implantation. RESULTS: All animals survived the initial aortic allograft operation. Six animals died postoperatively (1 of graft necrosis, 2 of pneumonia, and 3 of bronchial fistula). The remaining 9 animals were in good condition until they were euthanized. Stent removal was tolerated after 9 months in 3 animals. Progressive transformation of the arterial graft initially into extensive inflammatory tissue, and after 3 to 6 months into a tracheal tissue comprising a well-differentiated epithelium and cartilage was confirmed by histology. CONCLUSIONS: This study showed that regeneration of a functional tissue can be obtained after replacement of the carina with an aortic allograft. The origin and mechanisms of this regenerative process remains to be discovered. These results represent an important hope for the reconstruction of the carina after extensive resection, especially for cancer lesions. In human application, the systemic use of omentoplasty or myoplasty should further reduce its risk of complication.
Animals↗
[Interstitial lung disease in systemic sclerosis].
Interstitial lung diseases (ILD) associated with systemic sclerosis (SSc) are mainly encountered in patients with diffuse disease, although they may also be seen in patients with limited cutaneous SSc. ILD screening must be performed regularly, with high-resolution computed tomography and pulmonary function tests (TLCO). Up to 75% of patients with diffuse SSc develop a form of ILD. ILD remains stable in most patients and does not worsen. The nonspecific nature of SSc-associated ILD makes it different from idiopathic ILD and helps to explain its better prognosis. Nonetheless, ILD is one of the two leading causes of death in SSc patients. Treatment of SSc-associated ILD is not yet well codified. Antifibrotic treatments have not proved beneficial, and the efficacy of cyclophosphamide, which has been used to treat this condition for 15 years, has been shown to be very limited against SSc-associated ILD. A subgroup of patients with rapidly progressive ILD might benefit from intravenous cyclophosphamide pulses in association with 15 mg/d prednisone.
Anti-Inflammatory Agents↗
Sinonasal involvement in sarcoidosis: a case-control study of 20 patients.
We conducted a retrospective single-center study to describe the clinical features of sinonasal sarcoidosis (SNS) and to determine whether SNS is associated with a particular clinical phenotype of sarcoidosis. Twenty patients with histologically proven SNS (men/women, 7/13; mean age, 32 +/- 9 yr) were compared with control patients with sarcoid but without sinonasal (SN) involvement. Each patient was matched with 2 controls for the date of admittance in our institution. SN involvement occurred in the course of previously known sarcoidosis in 8 patients, whereas it preceded disease diagnosis in 12 patients. Among these 12 patients, 4 initially presented with strictly isolated SNS and 8 had other associated signs related to sarcoidosis. The most common symptoms were stuffiness (90%), anosmia (70%), and rhinorrhea (70%). Lupus pernio was frequent (50%). Local examination was constantly abnormal and showed hypertrophy (75%) and purplish coloring of the nasal mucosa with granulations (50%) on the septum and/or inferior turbinates. Computed tomography scans showed medial lytic lesions, mainly of the septum and/or the turbinates in about half the cases. All patients had negative antineutrophil cytoplasmic antibodies. Patients with SNS had significantly more frequent and severe involvement of vital organs than controls, had a longer history of sarcoidosis, and required systemic treatment more frequently (100% vs. 57.7%, p < 0.001) and for a longer time (78 +/- 42 mo vs. 29 +/- 18 mo, p < 0.0001). Corticosteroids maintenance dosage was high (10.5 +/- 6 mg daily) and mainly depended on SN involvement. Although rare, SN involvement is a severe and recalcitrant manifestation of sarcoidosis representing a therapeutic challenge.
Adult↗
Real-time RT-PCR detection of CK19, CK7 and MUC1 mRNA for diagnosis of lymph node micrometastases in non small cell lung carcinoma.
Metastatic lymph nodes (LNs) are the major prognostic factor in resected non small cell lung carcinoma (NSCLC). However, almost 50% of pN0 patients relapse, suggesting metastatic cells undetected by current staging procedures. A combination of markers [cytokeratins 19 and 7 (CK19, CK7) and mucin type 1 (MUC1) mRNAs] was therefore evaluated by real-time RT-PCR in order to detect occult cancer cells. Forty-three NSCLC tumor samples, 4 micrometastatic, 6 metastatic and 84 histologically negative mediastinal LNs from 19 patients with NSCLC were evaluated as well as blood mononuclear cells from 29 healthy volunteers and 17 benign LNs. When tested on cell lines, RT-PCR was particularly efficient for evaluation of CK19, CK7 and MUC1 mRNA expression. All tumor samples were positive for at least 1 marker and 74% of samples were positive for all 3 markers. CK7 and CK19 mRNA were not detected in benign LN and blood cells from healthy donors in contrast with MUC1 mRNA. Only CK7 and CK19 mRNA were therefore used for evaluation of mediastinal LNs: the 6 histologically metastatic and the 4 micrometastatic LNs were positive for at least one marker. Among the 84 histologically negative LNs, 6 (7%) were positive for at least one marker, potentially changing the stage of 2 out of 19 patients. In conclusion, in our feasibility study, parallel molecular detection of CK19 and CK7 mRNA can be considered a specific diagnostic tool for the assessment of microscopic lymphatic spread. Its prognostic impact remains to be evaluated in a prospective study.
Aged↗
Tracheal regeneration following tracheal replacement with an allogenic aorta.
BACKGROUND: Tracheal replacement remains an unsolved surgical problem. Attempts to use tracheal substitutes have failed to achieve reliable results. In this study, tracheal regeneration was obtained after tracheal replacement with an allogenic aorta. METHODS: Twenty female sheep underwent a 8-cm tracheal replacement with a fresh aortic allograft. In the six last animals, aortic grafts came from male sheep. A stent prevented airway collapse. No immunosuppressive therapy was used. Aortic segments were retrieved at regular intervals up to 16 months. A polymerase chain reaction for the SRY gene was performed in specimens with aortic grafts from male sheep. RESULTS: All animals but one survived the operation without complications. Clearly identified between the suture lines, the aortic segments were completely transformed into a tracheal structure. Histology showed initially an inflammatory reaction with proliferation of a squamous epithelium followed by mucociliary epithelium and newly formed cartilage rings. SRY gene was not found in newly formed cartilage rings showing that the regeneration originated from recipient cells. CONCLUSIONS: This study presents a new type of tissue regeneration and brings hopes to the treatment of extensive tracheal lesions.
Animals↗
Analysis of autoantibody repertoires in small- and medium-sized vessels vasculitides. Evidence for specific perturbations in polyarteritis nodosa, microscopic polyangiitis, Churg-Strauss syndrome and Wegener's granulomatosis.
In order to identify new antibody reactivities, we have used a quantitative immunoblotting technique on extracts of normal human tissues to analyze the repertoires of serum IgM, serum IgG and purified IgG autoantibodies of patients with systemic vasculitides. Patients fulfilled the American College of Rheumatology and Chapel Hill criteria for the diagnosis of polyarteritis nodosa (PAN) (n=8), PAN related to hepatitis B virus (HBV) infection (n=5), Wegener's granulomatosis (WG) (n=6), microscopic polyangiitis (MPA) (n=18) or Churg-Strauss syndrome (CSS) (n=8). Sera from patients with chronic HBV infection without PAN (n=5) and age- and gender-matched healthy individuals (n=45) were used as controls. In the lung extract, IgM from 12/18 MPA patients reacted with high intensity with a 50 kDa band and serum IgG from 3/8 CSS patients bound to a 70 kDa protein band. In the artery extract, serum IgG from 6/18 MPA patients bound to an 85 kDa antigen, whereas purified IgG from all WG patients tested bound to a 28 kDa protein band and IgM from CSS patients bound to 2 main antigens of 38 and 60 kDa. These results provide evidence for the specificity of autoantibody repertoires from patients with PAN, WG, CSS and MPA.
Adolescent↗
[Guidelines for the macroscopic studies of surgically resected lung specimens. Proposal for a anatomo-pathologic standardized form for the examination of pulmonary cancer].
We present practice guidelines for the examination of lung specimens removed for cancer, and pulmonary biopsies performed for interstitial lung diseases. In addition, we propose a standardized form for the reporting of lung cancer. This approach takes place in looking for better quality and should facilitate the use of the morphologic data, particularly in multicentric studies.
Biopsy↗
Acute respiratory failure after interferon-gamma therapy of end-stage pulmonary fibrosis.
Interferon (IFN)-gamma was recently proposed as a treatment for idiopathic pulmonary fibrosis. We report on four patients who developed acute respiratory failure with new alveolar opacities after 2 (two patients), 6, and 35 injections of IFN-gamma-1b. All four patients had advanced idiopathic pulmonary fibrosis (total lung capacity less than 45% predicted or carbon monoxide diffusion capacity less than 30% predicted), and two patients had familial pulmonary fibrosis. No other cause of deterioration was found. Refractory hypoxemia led to death in three cases and to lung transplantation in one case. Pathologic studies in two patients showed diffuse alveolar damage lesions with preexisting usual interstitial pneumonia. These cases suggest that IFN-gamma therapy can induce an acute respiratory failure in patients with end-stage idiopathic pulmonary fibrosis.
Acute Disease↗
Long-term evaluation of the replacement of the trachea with an autologous aortic graft.
BACKGROUND: Tracheal reconstruction after extensive resection remains a challenge in thoracic surgery. The goal of this experimental study was to analyze the long-term evolution of tracheal replacement using an autologous aortic graft. METHODS: In 21 sheep, a 5-cm segment of the cervical trachea was replaced by a segment of the descending thoracic aorta that was reconstructed to a prosthetic graft. Because of the airway collapse reported in a previous series, a permanent (n = 13) or temporary (n = 8) stent was systematically placed in the lumen of the graft. Clinical, bronchoscopic, and histologic examinations were performed up to 3 years after implantation. RESULTS: All animals survived the operation with no paraplegia. In the group with a permanent stent, three complications occurred: one stent displacement, one laryngeal edema, and one infection. Stent removal was tolerated after 6 months in the group with a temporary stent. Histologic examination showed a progressive transformation of the arterial segment into first extensive inflammatory tissue with a squamous epithelium, and after 6 to 36 months well-differentiated tracheal tissue including a continuous mucociliary epithelium and regular rings of newly formed cartilage. CONCLUSIONS: An autologous aortic graft used as a substitute for extensive tracheal replacement in sheep remained functional for periods up to 3 years. The progressive transformation of the graft into a structure resembling tracheal tissue seems to be a key factor in long-term patency. The mechanism of this regenerative process and the possibility of using arterial homografts, which would make clinical application easier, remain to be evaluated.
Animals↗
Three-dimensional characterization of pathologic lesions in pulmonary langerhans cell histiocytosis.
The characteristic lesions of pulmonary Langerhans cell histiocytosis (LCH) associate destructive granulomas containing large numbers of Langerhans cells and cysts. The lesions are usually considered to develop around small airways, and cysts are thought to result from destruction of the bronchiolar wall by the granulomatous reaction. However, the extent to which the granulomatous reaction is truly bronchocentric remains unknown, and the mode of formation of the cysts has not been defined. By using serial sections, this study aimed to explore further the relationships between pulmonary LCH lesions and distal airways, and the development of cysts. The results demonstrated that the granulomatous process of pulmonary LCH affected exclusively small airways, in an acinar distribution. The lesions extended without interruption along the bronchiolar axis, forming a continuous sheath around distal airways. The granulomatous reaction seemed to progress along the bronchiolar axis over time, extending the abnormalities in both the proximal and distal directions. Cystic lesions resulted from the destruction of the bronchiolar wall and progressive dilatation of the lumen, subsequently circumscribed by fibrous tissue. Because pulmonary LCH lesions affect and progressively destroy distal airways, it may be proper to consider the disease a bronchiolitis rather than an interstitial lung disorder.
Adult↗
Surgical resection of lung cancer in patients with underlying interstitial lung disease.
BACKGROUND: The association between interstitial lung disease (ILD) and an increased risk of developing lung cancer has been reported. The goal of this retrospective study was to determine the outcome of lung cancer resection among patients with ILD. METHODS: Between January 1979 and March 1999, 27 patients with both lung cancer and ILD were identified. Seven patients with poor pulmonary function tests or distant metastases underwent medical treatment and were excluded from this study. Twenty patients treated by surgical resection were analyzed. RESULTS: Various types of ILD such as sarcoidosis (n = 7), idiopathic interstitial pneumonia (n = 4), histiocytosis X (n = 4), pneumoconiosis (n = 4), and amiodarone-induced ILD (n = 1) were observed. Tumors were located in the peripheral part of the lung in 16 cases. The most frequent tumor cell types were squamous and adenocarcinoma. The resections consisted of lobectomy (n = 16), bilobectomy (n = 1), and pneumonectomy (n = 3). Most cancers were stage I (n = 10) or II (n = 6). There was no postoperative death. The postoperative course was uneventful in 16 cases. The majority of patients (70%) did not experience respiratory insufficiency during the follow-up period. The actuarial 2-year and 5-year survival rates were, respectively, 83.5% and 66.4%. CONCLUSIONS: In this series, the long-term survival of patients who had lung cancer resection appeared to be not affected by the association with ILD. This could be explained by an adequate preoperative selection based on pulmonary function tests and a preferential choice for lobectomies. Thus, surgical resection should be offered to properly selected patients with lung cancer and underlying ILD.
Adult↗
[Pulmonary veno-occlusive disease in a patient with HIV infection. A case report with autopsy findings].
We relate the autopsy findings of a case of pulmonary veno-occlusive disease which occurred in an HIV-infected intravenous drug abuser. This exceedingly rare disease, of unknown cause, is responsible for 10% of primary pulmonary hypertension. Histologically, the disease is characterized by a fibrous intimal thickening of small and medium sized pulmonary veins associated with congestive and dilated capillary network and alveolar haemorrhage. The occurrence of primary pulmonary hypertension in HIV positive patients is 25 times more frequent than in the general population. This is the third reported case of pulmonary veno-occlusive disease occurring in a HIV positive patient. It suggests the role of HIV in the pathogenesis of these vascular lesions.
Adult↗
Ground-glass computed tomography pattern in chronic beryllium disease: pathologic substratum and evolution.
Five cases of chronic beryllium disease with predominant or isolated diffuse ground-glass lung opacities on computed tomography are reported with correlation to lung pathology. The ground-glass attenuation was either homogeneous and isolated (n = 1) or patchy and clearly predominant (n = 4) over linear and nodular opacities. In 4 cases, histologic samples showed a prominent diffuse involvement of the alveolar-capillary walls by florid granulomas. Evolution under corticosteroid was remarkable by the appearance of small-sized cysts in 3 cases.
Adrenal Cortex Hormones↗