Peaks of transforming growth factor-beta mRNA in alveolar cells of lung transplant recipients as an early marker of chronic rejection.

BACKGROUND: Chronic lung rejection (CLR) induces a fibroproliferative disorder leading to the occlusion of small airways. It has emerged as the major factor limiting the survival of lung transplant recipients. Predictive markers of CLR are lacking, and its diagnosis is generally ascertained when the fibrosis process is irreversible. METHODS: We have quantified the expression of transforming growth factor-beta (TGF-beta), a critical mediator of fibrogenesis, in alveolar cells from lung transplant recipients using a competitive reverse transcriptase polymerase chain reaction method. RESULTS: We have shown that patients with CLR presented marked peaks of TGF-beta mRNA expression, in contrast with patients without CLR. These peaks preceded the diagnosis of CLR by several months in two of three patients who died within 2 years of diagnosis. CONCLUSIONS: Our data suggest that TGF-beta expression in alveolar cells could serve as an early predictive and prognostic marker of chronic lung rejection.

AIDS-related primary brain lymphomas: histopathologic and immunohistochemical study of 51 cases. The French Study Group for HIV-Associated Tumors.

Fifty-one cases of acquired immunodeficiency syndrome (AIDS)-related primary brain lymphomas (AR-PBL) were investigated for clinical characteristics; human immunodeficiency virus (HIV)-associated disorders; histopathologic features; immunophenotype; Epstein-Barr virus (EBV) infection; and, when frozen tissue was available, oncogene rearrangements. AR-PBL occurred late in the course of AIDS and were usually associated with other systemic or cerebral disorders and with a low level of CD4 lymphocytes. All cases were high grade lymphomas according to the Working Formulation or updated Kiel classification, and often displayed a multifocal pattern. Thirty cases were classified as immunoblastic with plasmacytic differentiation, 18 cases were large cell lymphomas with an immunoblastic component or centroblastic polymorphic lymphomas, and 2 were small noncleaved non-Burkitt lymphomas (Working Formulation). This latter category is classified as Burkitt's-like lymphoma in the REAL nomenclature. One case could not be classified because of necrosis. AR-PBL showed a high level expression of activation and adhesion molecules. The presence of EBV was detected in most cases, and, when PCR was used, this was a constant finding. bcl-2 oncoprotein and latent membrane protein-1 (LMP-1) were strongly expressed. None of the tested cases expressed p53, or were rearranged for bcl-2 or c-myc oncogenes. This study confirms the immunophenotypic specificity of AR-PBL, which may reflect the special immune status of the brain.

B-cell pulmonary lymphoma: gene rearrangement analysis of bronchoalveolar lymphocytes by polymerase chain reaction.

STUDY OBJECTIVES: Non-Hodgkin's lymphomas (NHLs) are clonal proliferation of B or T lymphocytes. Assessment of clonality in lymphoid proliferations uses immunochemistry and, recently, molecular biology. The aim of our study is to assess the role of immunoglobulin gene rearrangement analysis on bronchoalveolar lymphocytes to aid in the diagnosis of B-cell pulmonary NHL. PATIENTS AND METHODS: The study took place in a university hospital. There were seven consecutive patients with B-cell-type pulmonary lymphoma and nine control subjects. Gene rearrangement analysis using polymerase chain reaction (PCR) technique was performed on alveolar lymphocytes recovered by BAL. RESULTS: Analysis of the immunoglobulin heavy chain gene rearrangement showed a predominant clonal alveolar lymphocyte population in six of seven patients while all control subjects showed germline pattern. CONCLUSIONS: Gene rearrangement analysis by PCR of alveolar lymphocytes would appear to be sensitive in patients with B-cell pulmonary NHL (six of seven patients) and specific (zero of nine in the control group). This simple test should be added only in the analysis of cells recovered by BAL in patients with suspected primary and secondary B-cell pulmonary NHL.

Nebulized cyclosporine for prevention of acute pulmonary allograft rejection in the rat: pharmacokinetic and histologic study.

BACKGROUND: With regard to limiting the systemic effects of cyclosporine A and obtaining better control of acute pulmonary allograft rejection, local immunosuppressive therapy with aerosolized cyclosporine A seems of interest. Given the in situ immunologic mechanisms of acute rejection, as well as the anatomic structure of the lung, this therapy is feasible as previously described by others. The aim of our study is to determine the pharmacokinetic parameters of nebulized cyclosporine A and the best modalities of administration. METHODS: In a pharmacokinetic study, the cyclosporine A was given either by intramuscular injection (10 mg/kg) or by aerosol at 10 and 25 mg/kg doses; 70 rats were killed at 25 and 50 minutes and 2, 4, 6, 8, 12, 24, or 48 hours after cyclosporine A administration. Cyclosporine A levels were measured in whole blood and in the lung. The areas under the concentration time curves were determined. Twenty-four lung transplantations were then performed. The rats were killed on postoperative day 9. Acute rejection was scored on a scale of 0 to 4, and cyclosporine A trough levels were measured in the lung and in the blood. RESULTS: With a jet nebulizer, the mass median aerodynamic diameter was 2.5 microns, with a standard geometric deviation of 2.3. In blood, the area under the concentration curve was greater for intramuscular (80.6 ng.hr/ml) than for aerosol administrations at 10 (15.1 ng.hr/ml) and 25 mg/kg (41.0 ng.hr/ml) doses. In the lungs, the area under the concentration curve was greater for the aerosol route at 25 mg/kg doses (588 ng.hr/mg) than for the low-dose (200 ng.hr/mg) or intramuscular administration (200 ng.hr/mg). The lung targeting index of cyclosporine A (ratio area under the concentration curve-lungs/area under the concentration curve-blood) was greater for both aerosol administrations than for the intramuscular route. In the study of the prevention of acute rejection, rats without immunosuppression (n = 6), rats receiving daily doses of cyclosporine A intramuscularly (10 mg/kg), and rats with aerosolized cyclosporine A daily (10 and 25 mg/kg/day) showed mean grades of acute rejection of, respectively, 4, 2.03 +/- 0.27, 2.33 +/- 0.52, and 2.17 +/- 0.46. The deposition of nebulized cyclosporine A was lower in transplanted than in native lung. CONCLUSIONS: Nebulized cyclosporine A allows better pulmonary concentration than intramuscular administration, and results in lower systemic levels. Prevention of acute rejection is as good with aerosolized cyclosporine A as with intramuscular cyclosporine A. This first pharmacokinetic study of nebulized cyclosporine A could lead to clinical applications.

[Cerebral germ cell tumors in adults. A retrospective study of 19 cases]. / Les tumeurs germinales cérébrales de l'adulte. Etude rétrospective de 19 cas.

The authors report on the retrospective analysis of 19 patients with primary cerebral germ cell tumors which were treated between 1965 and 1993. Median age is 18 years (extremes: 16-55 years). There were 16 men and three women. The location of the primary tumor was the pineal area in six patients, suprasellar and hypothalamic area in five patients and other areas in eight patients. The histological pattern was non seminoma in six patients, dysgerminoma in eight; however no histological sample was obtained in five patients who did not have any particular characteristics (either cytological abnormalities or elevated tumor marker level). Three patients were treated by surgery only, eight patients received exclusive radiotherapy and eight patients had first line chemotherapy and further cranial irradiation. One was lost to follow-up. Six of eight assessable patients with dysgerminoma are alive with non evolutive disease (NED) after 15 to 176 month of follow-up. One out of five assessable patients with non seminomatous tumor in NED (163 month of follow-up). Finally all five patients who have no histological subtyping are alive with NED at 24 to 138 months. The standard treatment of dysgerminoma is currently first line chemotherapy followed by relatively low-dose and limited irradiation; the standard treatment of non-seminomatous cerebral germ cell tumor is chemotherapy, the study of which is warranted with the aim to decrease the toxicity and to increase the efficacy.

[Merkel cell carcinoma: primary cutaneous neuroendocrine tumor]. / Carcinome à cellules de Merkel: tumeur neuroendocrine cutanée primitive.

Merkel cell carcinoma is a neuroendocrine primitive tumor of the skin. We report a case who develops node and visceral metastasis, and dead. The clinical presentation, diagnosis, histology, immunocytochemistry, treatment and prognosis of this tumor will be discussed.

[Alveolar microlithiasis. Non-invasive diagnosis using alveolar lavage and technetium scintigraphy]. / Micro-lithiase alvéolaire. Diagnostic non invasif par lavage alvéolaire et scintigraphie au technetium.

A new case report of alveolar micro-lithiasis shows the diagnostic interest of two non invasive explorations to affirm a radiologic suspicion. Technetium showed calcium in the lung. The broncho-alveolar lavage, realised with a big quantity of fluid, removed the microliths. These two technics together avoid pulmonary biopsy.

[Low cost telepathology]. / Télépathologie à moindre coût.

Low cost, high-quality consumer-type digital cameras are now available on the market to be used for taking macrophotographs and microphotographs by simply fixing the camera over the eyepiece of a conventional light microscope using an adaptator. The quality of the images obtained is as good as obtained with more expensive materials using Tri CCD cameras. Using the JPEG format for compression, the image file size is approximately 180 Ko. We present a low cost approach we have tested for one year in our pathology department.

[Pulmonary papillomatosis]. / La papillomatose pulmonaire.

The authors report a case of a 30 year old woman with juvenile laryngeal papillomatosis (JLP) who subsequently developed intra-alveolar papillomas. These papillomas demonstrated a marked pseudo-neoplastic loco-regional invasive activity, but did not possess the histological criteria of malignancy and were treated by pneumonectomy and lobectomy.

[Noninvasive diagnosis of alveolar microlithiasis by Tc99m-MDP scintigraphy and alveolar lavage]. / Diagnostic non invasif de la microlithiase alvéolaire par la scintigraphie aux Tc99m-MDP et le lavage alvéolaire.

In a new case of alveolar microlithiasis we report the diagnostic value of two non-invasive examinations. In agreement with the histo-chemical date, scintigraphy with technetium shows an abnormal pulmonary fixation as evidence of the presence of intra-pulmonary calcium. The demonstration of micro-lithiasis in the alveolar lavage liquid, which requires a particular technique, confirms the diagnosis and avoids an open lung biopsy.

[Myxoid liposarcoma of the mediastinum]. / Liposarcome myxoïde du médiastin.

We describe a mediastinal myxoid liposarcoma case in a 47-year-old woman who complained of dyspnea. This kind of tumor is rare and becomes symptomatic by compression on mediastinal structures, especially on the respiratory tract. These neoplasms are therefore often voluminous at the time the diagnosis is made. Histopathologic examination is always necessary as much for diagnosis as prognosis. Surgery, whether radical or palliative, obtain the best therapeutic survival results in myxoid liposarcoma of the mediastinum.

[Report of 2 cases of pleural recurrences of surgically treated bronchogenic carcinoids. Diagnostic and therapeutic problems]. / A propos de 2 récidives pleurales de carcinoïdes bronchiques opérés. Problèmes diagnostique et thérapeutique.

Recurrence after surgery for bronchial carcinoid tumors is very uncommon in cases of typical tumors and occasionally seen in cases of atypical tumors. We observed two cases of recurrence in an unusual location, the pleura. Somatostatin analog and MIBG scinigrams were useful for diagnosis. Treatment required surgical excision of the relapsing tumor, cytoreductive hepatic surgery or hepatic arterial chemoembolization for liver metastases, chemotherapy, interferon, radionuclide therapy, and somatostatin analogs for carcinoid syndrome.