Biomedical subjects
Publications and source records attributed to L Garbe.
We report a case of early Wegener's disease mimicking tuberculosis in a 36 year old man. Lungs are solely affected for 6 months. Unusual appearance of radiographic features with large apical excavations explain the delai for the diagnosis. We discuss morphological features in the lungs and kidney.
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BACKGROUND: Cytomegalovirus (CMV) frequently is observed in immunocompromised hosts. The aim of this study was to report cases of ventilator-associated CMV pneumonia diagnosed by pathologic examination in intensive care patients without acquired immunodeficiency syndrome or hematologic malignancy or who were not receiving immunosuppressive agents. METHODS: From June 1, 1989, to May 31, 1994, 2,785 patients were hospitalized. During the study period, 60 autopsies and 26 open-lung biopsies were performed in nonimmunocompromised patients who were seen with acute respiratory failure and/or symptoms suggestive of ventilator-associated pneumonia. Cytomegalovirus pneumonia was diagnosed using pulmonary samples by the identification of large cells with large nuclei containing a basophilic or eosinophilic inclusion surrounded by a light halo. These typical findings always were associated with a diffuse interstitial pneumonitis. RESULTS: Cytomegalovirus pneumonia was diagnosed after histologic examination in 25 patients. The reason for admission to the intensive care unit was major surgery in 13 patients and medical problems in 12 patients. Ventilator-associated CMV pneumonia was diagnosed by histologic examination 22.4 +/- 8.8 days after admission to the intensive care unit (median 18 days; range 10-40 days). The clinical description was similar with the 25 patients who were seen with ventilator associated CMV pneumonia and the 61 patients without ventilator-associated CMV pneumonia. However, there was a more severe hypoxemia 72 +/- 16 vs. 95 +/- 41 mmHg, P < 0.05) and a higher Weinberg's radiologic score (9.2 +/- 1.9 vs. 7.4. +/- 2.7, P < 0.05) in the ventilator-associated CMV pneumonia group. Diagnosis of ventilator-associated CMV pneumonia was made for 9 of 17 patients when shell-vial culture technique using fluorescein-labelled antibody E 13 was performed on bronchoalveolar lavage products. Four of the eight patients treated by ganciclovir therapy died of multiple organ dysfunction syndrome. CONCLUSIONS: The diagnosis of ventilator-associated CMV pneumonia should not be excluded in intensive care patients, even those without acquired immunodeficiency syndrome, hematologic malignancy, or immunosuppressive agents on admission.
Acute inflammation in the lung is characterized by a phase of tissue injury followed by a phase of tissue repair. When the latter is excessive, fibrosis occurs. Alveolar macrophages (AM) can produce cytokines involved in both phases of acute lung inflammation, notably interleukin-6 (IL-6), involved in injury and transforming growth factor-beta (TGF-beta), mediating repair. We hypothesized that AM were activated in both phases, and studied IL-6 and TGF-beta production by AM during complications of lung transplantation, acute rejection (AR), and cytomegalovirus pneumonitis (CMVP). In addition, we analyzed these cytokines in bronchiolitis obliterans (BO), a fibrotic complication of lung transplantation linked to previous AR and CMVP. At the onset of AR and CMVP, IL-6 secretion increased, whereas AM TGF-beta content was increased, but not its secretion. In contrast, with time, IL-6 reached control value whereas TGF-beta secretion rose significantly. In BO, IL-6 was not oversecreted, but TGF-beta increased, notably before functional abnormalities occurred. These results show that during acute complications of lung transplantation, AM display an early activation with oversecretion of IL-6, which is involved in tissue injury, counterbalanced by a late activation in which TGF-beta predominates, mediating tissue repair. The results provide new insights into the pathogenesis of BO, which is linked to acute complications of lung transplantation through this biphasic AM activation.
Human papillomaviruses (HPV) have been implicated in the pathogenesis of human squamous cell carcinoma, specially of cervical carcinomas. In previous studies concerning primary lung cancer, DNA of HPV subtypes was detected by in situ hybridization or polymerase chain reaction (PCR), up to 30% of the cases, namely in squamous cell carcinomas. A series of 31 frozen biopsies of lung carcinomas (surgical biopsies or through fiber optic bronchoscopy) were examined for the presence of HPV DNA by nested PCR. Primers for the two steps were type-specific primers (6/11-16 and 18; kit Amplicis-HPV) for the transforming region of HPV. HPV-DNA was found in five tumors: in two of 18 cases of squamous cell carcinoma (11%), in one of four cases of adenocarcinoma, in one of six cases of small cell carcinomas and in the unic case of neuro-endocrin carcinoma. No case of the two large cell undifferentiated carcinomas was positive. There were three cases of HPV 6/11, one case of HPV 16, and one sample positive for HPV 6/11 and HPV 18. No morphologic changes consistent with HPV lesions were observed. The frequency of 11% among the squamous cell carcinomas is near those found by previous studies (9 to 20% for HPV 6-11-16-18). For the first time, HPVs have been detected in neuro-endocrin tumors, and this have to be confirmed by studies of many more cases. So HPV might play a role as promoter in carcinogenesis of any types of lung carcinoma, although at a low frequency.
The purpose of this prospective postmortem study was to assess the diagnostic accuracy of bronchoscopic techniques (bronchoalveolar lavage [BAL] and protected specimen brush [PSB]) and nonbronchoscopic techniques (blind bronchial sampling [BBS] and mini-BAL) in the diagnosis of ventilator-associated pneumonia (VAP). The results of each technique were compared with histology and culture of lung tissue specimens obtained by surgical pneumonectomies in 38 patients who died after at least 72 h of mechanical ventilation. Histology was positive for VAP in 18 patients and negative in 20 patients. There were 12 definite VAP (positive histology and positive lung cultures) and 6 histologic VAP (positive histology and negative cultures). Clinical pulmonary infection score (CPIS) at a threshold of 6 achieved a sensitivity of 72% and a specificity of 85%. When the CPIS was combined with the logarithmic concentration of the predominant microorganism obtained from the BBS sample culture, specificity was increased to 95%, for a threshold of 10. Using 10(3) cfu/ml as the threshold of positivity for cultures obtained with PSB and mini-BAL samples and 10(4) cfu/ml for cultures obtained with BBS and BAL, the respective sensitivities of these techniques for definite VAP were 42, 67, 83, and 58%. The sensitivity of BBS was significantly higher than that of PSB (p < 0.05). The area under the receiver operator characteristic curve was significantly greater for BBS than PSB (p < 0.05). Given that it is more sensitive and noninvasive, BBS is preferable to PSB for the diagnosis of VAP.
We conducted a review of all the bronchoscopies performed at our institutions for benign tumors from 1980 to 1991 to determine the endoscopic characteristics of these lesions. We reviewed the charts, the endoscopic characteristics from our video records, and finally the pathologic findings of these cases. We tried to identify the effectiveness of laser resections in each group. Of a total of 3,937 patients, 185 (4.7%) were benign tumors. On these patients, 317 procedures were carried out. There were 3 myoblastomas, 53 papillomas, 1 adenoma, 8 chondromas, 4 fibromas, 45 hamartomas, 15 hamartochondromas, 6 lipomas, 19 angiomas, 5 leiomyomas, 4 schwannomas, 1 neurofibroma, and 21 amyloidomas. Results of laser resection were "very good" in 115 (62%) and "good" in 70 (38%). Complications were minimal: two mediastinal emphysemas, one pneumothorax, and one anesthesia-related cardiac arrest leading to the single death in this series. In general, benign tumors of the proximal endobronchial tree responded well to laser resection when their endoscopic appearance is recognized and prognosis known. Even when recurrent, repeated procedures can be performed easily with good results. This series is probably the largest in the world's literature about endoscopic recognition and the role of laser resection in patients presenting with benign endobronchial tumors.
Between may 1988 and march 1993, twenty five double lung transplants were performed and five heart/lung transplants. Lung function tests (EFR) were performed on these patients for a period of 19.2 +/- 3.4 months. The aim of this study was two-fold. First, to report our overall results and to estimate the role of the single breath nitrogen washout test (N2 slope) in the early detection of chronic rejection (RC). Secondly, to assess the diagnostic value of EFR in the discrimination of acute rejection (RA) and of cytomegalovirus pneumonitis (PCMV). There were 41 episodes of RA and 21 episodes of PCMV and they were analysed as a function of the presence or absence of RC. In the absence of RC, RA produced no change in EFR and PCMV was accompanied by a pure restrictive ventilatory defect. On the otherhand, RA and PCMV lead to a worsening of obstruction and an hypoxaemia which characterises RC. The diagnosis of RC was made, on average, 14.4 +/- 2.9 months after surgery. However, from the sixth month the nitrogen slope was significantly increased and other parameters of EFR (particular maximal flows at low lung volume) remained normal. Thus, our results suggest that the N2 slope, measured in the absence of any evidence of acute rejection, constitutes an early test for chronic rejection. When its pathological rise is compared to the results of histology (presence or absence of RC), it shows a sensitivity of 0.94 and a specificity of 0.93.
Human papillomaviruses (HPV) have been implicated in the pathogenesis of human squamous cell carcinoma, especially of cervical carcinomas. In two previous studies concerning squamous cell carcinomas of the lung, DNA of HPV subtypes 6/11/16/18 (and 31/33/35 for one study) was detected by in situ hybridization in 7% to 30% of the cases. A series of 31 frozen biopsies of lung carcinomas were examined for the presence of HPVDNA by nested polymerase chain reaction (PCR). Type-specific primers (6/11, 16 and 18; Amplicis HPV(R)) located in the E6 or E7 transforming region of HPV were used. HPV DNA was found in 2 of 18 cases (11%) of squamous cell carcinoma, in 1 of 4 cases of adenocarcinoma and in 2 of 7 cases of neuro-endocrine cancers. The two large cell undifferentiated carcinomas were HPV negative. There were three cases of HPV 6/11, one case of HPV 16, and one sample positive for HPV 6/11 and HPV 18. No any consistent morphologic change with HPV lesions could be observed whereas squamous metaplasia could be seen only in squamous cell carcinomas. The frequency of 11% among the squamous cell carcinomas is comparable to those previously reported in studies utilizing in situ hybridization. To our knowledge HPV DNA had never been detected previously in adenocarcinomas or neuro-endocrine tumors. This finding should be confirmed by the investigation of larger series, but suggests that HPV could play a role in carcinogenesis of different types of lung carcinoma, although at low frequency.
The objective of this study was to evaluate the potential role for single photon-emission computed tomography (SPECT) using technetium 99m-macroaggregated albumin for diagnosing rejection in lung transplant patients. SPECT results were compared with those obtained from transbronchial biopsy (TBB) in patients undergoing bronchoscopy during routine surveillance and in cases of clinical, radiographic, or physiologic suspicion of lung rejection. This prospective, nonrandomized study was conducted by the Marseille Lung Transplant Group, Marseille University Hospitals South. It included 26 lung transplant recipients (19 double-lung, four single-lung, and three heart-lung). For each patient, SPECT lung perfusion was performed before TBB as part of routine surveillance protocol and when clinically indicated. Routine surveillance included TBB at 1, 3, 6, 9, and 12 months and every 6 months thereafter. SPECT was always performed within the 24 h preceding TBB. Whenever the SPECT was abnormal, biopsies were obtained from an area corresponding to a region of hypoperfusion. Results of the study were based on 79 paired SPECT and TBB obtained from 26 patients. Concordance between SPECT and biopsy occurred in 71 instances (89.9%). Among 25 cases of normal SPECT, TBB was normal in 24 and revealed subclinical lung rejection in one. Among 54 cases of abnormal SPECT, TBB was also abnormal in 47 (87.0%), with lung rejection being the abnormality in 23 (46%). For pairs performed as part of the routine surveillance protocol (61 pairs), clinically silent lung rejection was diagnosed in 16 (26.2%). SPECT was abnormal in 15 of 16 instances and normal in only one; this patient had minimal rejection that resolved without treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Bronchiolitis obliterans (BO), a common complication in lung transplant recipients, is a fibrotic process probably related to acute rejection (AR) and cytomegalovirus pneumonitis (CMVP). Because the pathogenesis of pulmonary fibrotic diseases involves activation of alveolar macrophages (AM), the present study was carried out to determine if AM were activated during AR, CMVP, and BO. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured in 157 AM supernatants obtained from 29 transplant recipients by immunoradiometric assay. Five groups were analyzed: AR (n = 21), CMVP (n = 12), BO (n = 15), bacterial pneumonia (BP) (n = 8), and control subjects (n = 70). Cytokines were also assayed 15 d (n = 15) and 30 d (n = 9) after AR and 30 d (n = 9) after CMVP. Cytokine secretion was elevated during AR (TNF-alpha = 3,709 +/- 1,409 pg/10(6) cells, IL-6 = 5,482 +/- 2,058 pg/10(6) cells, p < 0.005), and they returned to control values within 15 d. A similar pattern was observed during CMVP (TNF-alpha = 5,000 +/- 2,773 pg/10(6) cells, IL-6 = 12,280 +/- 3,939 pg/10(6) cells, p < 0.005), and values returned to control levels within 30 d. During BP, cytokine production values were higher than control values, but to a lesser extent than in AR and CMVP (TNF-alpha = 2,502 +/- 1,072, p < 0.05; IL-6 = 3,734 +/- 1,440, p < 0.005). In contrast, cytokine secretion during BO was not statistically different from that of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
The authors report an analysis concerning the healing of tracheo-bronchial anastomoses after lung- and heart-lung transplantation. The present study includes 64 anastomoses selected from a total of 80 cases. Sixteen had to be excluded because of early post-operative death; none of these deaths was related to an air-way complication. Bronchial healing was assessed by bronchoscopic follow-up; the appearance of the suture-line was classified according to Couraud's grades. The initial reference was the examination at 2 weeks, which was compared to subsequent follow-up. At the initial assessment, 42 anastomoses were grade 1, 4 were grade II, and 18 were grade III. The subsequent anatomic result was satisfactory for 52 sutures (81%). The complications were malacia in 2 cases, stenoses treated with a stenting device in 4 cases, dehiscence in 6 cases. The duration of ischemia and postoperative mechanical respiratory support, as well as the proximal or distal site of the anastomosis appeared to be of significant prognostic value.
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In order to test the validity of the new 1987-UICC classification (4th ed.) for lung cancer, data from 456 patients who underwent pulmonary resection for bronchogenic carcinoma from 1980 to 1985 were analysed retrospectively. Overall survival rate was 32.7% at 5 years. Prognostic significance of the tumour formula (pTNM) was assessed by multivariate analysis: N lymph node involvement appeared to be the most pejorative factor (p < or = 10(-5)), followed by the T factor (p < or = 0.002) and the M factor (p < or = 0.01). Respective survival curves were compared. Excluding the correlation between T1 and T2 tumours, the prognosis became significantly more unfavourable as the values for the pTNM classification criterion rose. Differences in prognosis between stages I and II, II and III A, III B and IV were not statistically significant for methodological reasons and inappropriate regroupings. Thus, our results partially confirm the prognostic value of the new international staging system. Meanwhile, this classification constitutes a prerequisite for the evaluation of end-results of therapy and the estimation of prognosis.
The authors report an analysis concerning the healing of tracheo-bronchial anastomoses after lung- and heart-lung transplantation. The present study includes 64 anastomoses selected from a total of 80 cases. Sixteen had to be excluded because of early post-operative death; none of these deaths was related to an air-way complication. Bronchial healing was assessed by bronchoscopic follow-up; the appearance of the suture-line was classified according to Couraud's grades. The initial reference was the examination at 2 weeks, which was compared to subsequent follow-up. At the initial assessment, 42 anastomoses were grade I, 4 were grade II, and 18 were grade III. The subsequent anatomic result was satisfactory for 52 sutures (81%). The complications were malacia in 2 cases, stenoses treated with a stenting device in 4 cases, dehiscence in 6 cases. The duration of ischemia and post-operative mechanical respiratory support, as well as the proximal or distal site of the anastomosis appeared to be of significant prognostic value.
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We report a well-documented case of Castleman's disease which embodied all the main features of its localized forms, those most frequently described in the literature. This case was particular by its unusual intrapulmonary location and its intra-fissural development, which explains why the diagnosis was not considered preoperatively. A review of the literature showed that beside the localized forms of Castleman's disease multifocal forms have recently been reported; these have a much poorer prognosis, and their treatment has not yet been established.
Data from 452 patients who underwent pulmonary resection for a non small cell bronchogenic carcinoma from 1980 to 1985 were analysed retrospectively. The operative mortality rate was 5.5%. Mortality was significantly increased in patients who underwent enlarged resections for T4 tumors (20%; p < or = 0.05), and in patients who were 70 years and older (12.8%; p < or = 0.05). The overall 5-years survival rate was 32.7% at 5 years. Prognosis in patients who were 70 years and older was similar to that in younger patients. No difference in survival was observed in patients with lymph node metastases with regard to the operative procedure (pneumonectomy versus lobectomy). Survival in patients without lymph node metastases who underwent a lobectomy was similar to those who underwent a conservative resection. Prognostic significance of the histologic cell type and the tumor formula (pTNM) was assessed by multivariable analysis. There were statistically significant differences between squamous cell carcinoma and both adenocarcinoma (p < or = 10(-5)) and undifferentiated carcinoma (p < or = 0.01). This study confirmed the validity of the TNM classification (4th ed) for the accurate prognosis evaluation. Lymph node involvement appeared to be the most pejorative factor (p < or = 10(-5)).