Search

Since their discovery as pluripotent cytokines extractable from bone matrix, it has been speculated how bone morphogenetic proteins (BMPs) become released and activated from the extracellular matrix (ECM). In contrast to TGF-βs, most investigated BMPs are secreted as bioactive prodomain (PD)-growth factor (GF) complexes (CPLXs). Recently, we demonstrated that PD-dependent targeting of BMP-7 CPLXs to the extracellular fibrillin microfibril (FMF) components fibrillin-1 and -2 represents a BMP sequestration mechanism by rendering the GF latent. Understanding how BMPs become activated from ECM scaffolds such as FMF is crucial to elucidate pathomechanisms characterized by aberrant BMP activation and ECM destruction. Here, we describe a new MMP-dependent BMP-7 activation mechanism from ECM-targeted pools via specific PD degradation. Using Edman sequencing and mutagenesis, we identified a new and conserved MMP-13 cleavage site within the BMP-7 PD. A degradation screen with different BMP family PDs and representative MMP family members suggested utilization of the identified site in a general MMP-driven BMP activation mechanism. Furthermore, sandwich ELISA and solid phase cleavage studies in combination with bioactivity assays, single particle TEM, and in silico molecular docking experiments provided evidence that PD cleavage by MMP-13 leads to BMP-7 CPLX disintegration and bioactive GF release.

BACKGROUND Image-enhanced endoscopy enables real-time differential diagnosis of colorectal lesions through the observation of microvascular architecture. PURPOSE To evaluate the efficacy of using blue laser imaging (BLI) for capillary pattern analysis in the differential diagnosis of neoplastic and non-neoplastic lesions. PATIENTS AND METHODS This prospective study included 920 consecutive superficial lesions diagnosed in 457 patients. The capillary pattern was analysed using BLI-bright magnification on the basis of the Teixeira classification. Histopathology was used as the reference standard. RESULTS The adenoma detection rate was 42.3%, with a mean of 0.95 adenomas per patient. Neoplastic lesions were predominant (70.3%), of which 33 (5.1%) had advanced histology. Neoplastic progression was significantly increased in patients aged at least 50 years, in lesions at least 10 mm and in lesions located in the right colon (P

Objective: The objective of this study was to assess the results of completion pneumonectomy performed for non-small cell lung cancer, classified as second primary or recurrence/metastasis. Methods: From 1982 to 2000, 59 patients underwent completion pneumonectomy for lung cancer, classified second primary or recurrence/metastasis according to a modified form of Martini's criteria, after a mean interval from first resection of 60 months for second primary lung cancers and 19 months for recurrences/metastases. Results: Operative mortality was 3.4% and complications occurred in 30% of patients. Five-year survival rate for completely resected patients was 25% (median 20 months). No significant difference in long-term survival was detected between second primary and recurrent tumors; survival was not adversely affected by a resection interval of less than 2 years or less than 12 months. Conclusions: Completion pneumonectomy for non-small cell lung cancer is a safe surgical procedure in experienced hands; long-term survival is acceptable and the best results are obtained for stage I lung cancer. Distinction between second primary lung cancer and recurrence failed to demonstrate a prognostic value.

Seven patients who had undergone a pneumonectomy for lung cancer developed a second tumor in the remaining lung after a mean time of 28.5 months and underwent a further resection. Preoperative evaluation was based on standard functional tests and on the "stair climbing test". Three patients were operated on using an extracorporeal oxygenator to work on a collapsed lung, three using standard anesthesiologic techniques, and one using high-frequency jet ventilation. There was no operative mortality. Complications occurred in two patients, requiring a temporary tracheostomy in one case. No patient required home oxygen supplementation. Four patients died of metastatic disease after 4, 8, 10, and 12 months, while two patients are alive and free of disease after 83 and 9 months, one is alive and free of symptoms but with a local recurrence after 29 months. Lung resection for bronchogenic carcinoma on a single lung can be safely performed provided that careful clinical judgment is used; long-term survival can be achieved with the resection of the new tumor.

From 1980 through 1993 ten patients underwent concomitant coronary artery bypass grafting and lung resection via median sternotomy. In eight patients a lung malignancy was resected, of which one was a small cell lung cancer. The lung resection was carried out before cardiopulmonary bypass in eight patients and during cardiopulmonary bypass in two. Coronary artery bypass grafting was performed using saphenous vein in eight patients; internal mammary artery was used as arterial conduit in two patients. There was one postoperative death while postoperative complications during hospital stay occurred in two patients. Pulmonary bleeding did not occur in any patient in whom lung resection was performed either before or during cardiopulmonary bypass. Both the patients who had internal mammary artery grafting experienced complications related to an associated lobectomy. A staged procedure is advisable if internal mammary artery has to be used and a lobectomy is required. The long-term survival in the patients with lung cancer was less than expected but the number of patients is too small to draw definite conclusions.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon skin tumour characterized by a slow, infiltrative growth and marked tendency towards local recurrences. Wide surgical excision of 3-5 cm from the margins including the fascia is the recommended treatment. Mohs Micrographic Surgery has been shown to afford lower rates of recurrence. The Mohs-Tübingen technique is a variant indicated for very large excisions that allows a complete eradication of the tumour, preserving healthy tissues. We report the case of a 45 year-old man affected by DFSP of the right shoulder deeply infiltrating the muscles, referred to us for a recurrence after a large excision. We submitted the patient to Mohs-Tübingen surgery in collaboration with an orthopaedic surgeon due to the presence of muscular involvement of DFSP. Two surgical operations were necessary to obtain negative histology as the tumor was deeply infiltrating the prescapular muscles. After three years of follow-up, the patient did not have any recurrence and the normal mobility of the shoulder was preserved. Precocious diagnosis and adequate therapy are necessary for DFSP as not only the margins, but also the deep invasion of the tumor have to be carefully controlled.

We report on a patient who underwent a left pneumonectomy for a second primary lung cancer after a right upper lobectomy and upper chest wall resection for a superior sulcus tumor. Although the postoperative course was complicated by sputum retention which required a temporary tracheostomy the outcome was good and the patient is now living without supplementary oxygen supply. Left pneumonectomy may be considered in patients with previous contralateral lobectomy when the preoperative evaluation of the patient shows an acceptable predicted postoperative pulmonary function. A long-term cure and a good quality of life must, however, be offered.

Objective: To assess operative mortality (OM), morbidity and long-term results of sleeve lobectomies performed for non-small cell lung cancer (NSCLC) and carcinoids during a 35-year period. Methods: A retrospective review of patients who underwent a sleeve lobectomy for NSCLC and carcinoids was undertaken, univariate and multivariate analyses of factors influencing early mortality in NSCLC were performed and for this purpose the series was split into an early and a contemporary phase, the Kaplan‐Meier method was used to calculate the cumulative survival rate, and statistical significance was calculated with the log‐rank test. Causes of death were evaluated in relation to the stage of the disease. Results: OM for NSCLC was 14.6% in the early phase and 6% in the contemporary one; late stenosis occurred in 7.7% of NSCLC patients in the early phase and in 2% in the contemporary one. No OM or late stenosis occurred in carcinoid patients. Three, 5 and 10-year survival rates excluding carcinoids were 77, 62 and 31% for stage I(A‐B), 45, 34 and 27% for stage II(A‐B), 33, 22 and 0% for stage III(A‐B). The 10-year survival rate for carcinoids was 100%. There was no significant difference in long-term survival between stages II and III, while the difference between stage I and stages II and III was significant ðP , 0:001Þ: When survival was analyzed in relation to nodal status, 3, 5 and 10year survival rates were 71, 57 and 33% for N0 disease, 42, 33 and 22% for N1 disease, and 34 and 19% with the last observation at 82 months of 19% for N2 disease; there was no significant difference in survival between N1 and N2 disease. A second primary lung cancer occurred in six patients (3.7%) who underwent resection. Late mortality was not related to cancer in most stage I patients while in stages II and III patients it was related to local and distant recurrences. Conclusions: Sleeve lobectomy is a valid alternative to pneumonectomy: careful patient selection and surgical technique make it possible to achieve a mortality rate comparable to or lower than that for pneumonectomy along with a better quality of life. In addition, it allows further lung resection, if necessary. q 2002 Elsevier Science B.V. All rights reserved.

Four patients who previously underwent pneumonectomy for lung cancer, underwent a new contralateral resection for a metachronous cancer. Functional evaluation of these patients was not different from the standard one and included ECG, spirometry, blood gas analysis and a careful clinical evaluation. A femoro-femoral bypass was used in 2 patients to work on a collapsed lung, High Frequency Jet Ventilation was used in 1 while the last patient was hyperoxygenated and then ventilation was discontinued for the time required for the resections.Each method was free of complications. Operative mortality was nil. Two patients are alive free of disease at 66 and 14 months, two died for metastatic disease at 4 (N2 paratracheal nodes) and 12 months.Patients with a single lung should not be denied a further resection on contralateral lung. A routine evaluation of cardiopulmonary function may be sufficient but a more sophisticated evaluation including exercise oxygen consumption test, cardiac catheterization, lung perfusion scan, should be used when there is some doubt on the possibility of the patients to sustain the resection. Due to the high operative risk of this kind of patients mediastinoscopy should be performed even if preoperative CT scan of the chest shows minimally enlarged mediastinal nodes.

The possible role of magnesium sulfate (MgSO4) infusion in the prevention of atrial tachyarrhythmias after non-cardiac thoracic surgery was evaluated through a prospective study of two hundred patients who underwent non-cardiac thoracic surgery. The patients (who fulfilled the following requirements among others: no myocardial infarction in the previous six months, normal renal function, no use of digitalis or antiarrhythmic drugs, not undergone emergency operations or video-assisted thoracic surgery), were randomly assigned to receive MgSO4 infusion in all circumstances (Mg group), or either no treatment or, if aged over 70 or in cases of pneumonectomy or an intrapericardial procedure, application of digoxin starting on the day of operation (control group). 95 patients were enrolled in the Mg group and 105 in the control group. 93 patients in the Mg group and 101 in the control group were evaluated. Post-operative atrial tachyarrhythmias, mainly atrial fibrillation, occurred in 10 patients (10.7%) in the Mg group and in 27 (26.7%) patients in the control group (chi 2 = 7.009, df = 1. p = 0.008). It is concluded that infusion of MgSO4 is an effective means of reducing the incidence of atrial tachyarrhythmias after non-cardiac thoracic surgery.

A patient underwent a subtotal resection of the tracheobronchial carina for an obstructing endobronchial lesion. Preoperative biopsies of the lesion were not diagnostic. After resection, the histological examination of the specimen removed demonstrated an extramedullary plasmacytoma infiltrating the bronchial wall. Immunohistochemical studies showed monoclonality for kappa light chains. The postoperative course was uneventful and the screening for multiple myeloma was negative. No adjuvant treatment was given and the patient is currently alive and free of disease 63 months after the resection. Primary endobronchial plasmacytoma is a very rare disease; it is unclear which is the best treatment for endobronchial plasmacytoma. However, complete surgical resection has allowed a long-term survival, free of disease.

Vancomycin penetration into lung tissue was evaluated in thirty patients following the administration of 1 g of vancomycin as a 1 h i.v. infusion. Mean concentrations (range) of vancomycin in lung tissue were 9.6 (6.3-12.1) mg/kg at 1h, 5.7 (4.7-7.4) mg/kg at 2 h, 4.2 (0.8-6.5) mg/kg at 3-4 h, 2.4 (1.4-4.7) mg/kg at 6 h, and 2.8 (0.9-7.8) mg/kg at 12 h after the end of infusion. Ratios of lung tissue to serum concentration ranged 0.24 to 0.41 at 1 and 12 h, respectively. One of six patients observed at 6 h, and 3 of 7 patients at 12 h did not have detectable levels of vancomycin in lung tissue. A 1 h iv infusion of a 1 g dose of vancomycin does not achieve sustained lung concentrations above the MIC for susceptible staphylococci over a dosing interval of 12 h. Therefore, a more appropriate modality of administration, such as continuous infusion, should be considered.

From 1982 through March 1994, fourty-seven patients underwent completion pneumonectomy for a reappearing lung cancer, lung metastases, late complications, benign lung diseases, and early complication of bronchial or pulmonary artery sleeve resections. Intraoperative bleeding was higher than in standard pneumonectomy; there was one intraoperative mortality (2.3%). Operative mortality was 14.9% overall but was 3.6% in completion pneumonectomy for lung cancer, 20% for late complications and benign disease, and 57% for the treatment of early complications of sleeve resections. Three and five-year survival in patients with lung cancer who survived the operation was 43.8% and 28.7% according to the Kaplan-Meier method; no significant difference in long-term survival was present between patients with a second primary lung cancer or recurrence. Completion pneumonectomy is indicated in reappearing lung cancer and should be considered in benign disease when a less invasive procedure is not available. Completion pneumonectomy for the treatment of early complications of bronchial or pulmonary artery sleeve resections has a very high mortality but no alternative is available.

Pulmonary lymphangioleyomiomatosis (LAM) is a rare disease that affects only women. About one hundred cases are reported in the literature. This disease progresses to respiratory failure and its course can be slowed by hormonal therapy. A new case is reported; this woman was admitted to our Division for a right hydropneumothorax and after pleural drainage fluid demonstrated to be a chylous effusion; after a thoraco-abdominal CT scan the diagnosis of LAM was suspected. She was operated on after a few days because of continuous air and chyle leakage. A closure of lung leakage was performed with a stapler device that allowed the removal of a small specimen of lung for histopathological examination and a parietal pleurectomy was added with the aim of obtaining a pleural space obliteration. The histopathological examination revealed changes consistent with LAM and also positive was the hormonal steroid receptors assay. Adhesion of the lung to the chest wall was obtained but an antero-basal pouch persisted with continuous chylous leakage. A transposition of omentum into the chest was made with the aim of obliterating the pouch and favour chyle reabsorption and no drainage was left. Another CT scan demonstrated complete obliteration of the pouch and no fluid accumulation; the procedure proved to be successful and the patient was discharged with hormonal therapy.

The incidence of chylothorax after pleuro-pulmonary operations as well as its treatment is reported. Of 1744 operations performed postoperative chylothorax developed in 13 (0.74%). It resulted in two cases from the transection of the thoracic duct, in six from the transection of the so-called minor lymph channels, which drain lymph from mediastinal nodes straight into the thoracic duct or drain lung segments into the thoracic duct via the pulmonary ligament; the transection of these channels occurred during mediastinal lymphadenectomy or during the section of the pulmonary ligament. In 5 patients the site of leakage was not determined as reoperation was not required. Conservative treatment with low-fat diet and medium-chain triglycerides and/or total parenteral nutrition was attempted in all but one patient but was successful only in 5 cases whose mean losses were 292 ml/day. Seven patients were reoperated after a mean of 11 days; their mean losses were 930 ml/day. One patient was reoperated on the third postoperative day without attempting conservative treatment; his mean loss was 850 ml/day. Lymphadenectomy seems to be an important risk factor for postoperative chylothorax. Chyle leakage around 500 ml/day or higher that tends to decrease below 500 ml/day after a few days of dietary manipulation usually stops within 10-20 days, while leakage over 500 ml/day that does not tend to decrease below 500 ml/day seldom if ever stops without surgery, so that a more aggressive attitude is justified.

A rapid, sensitive and specific reversed phase HPLC method for the simultaneous assay of amiodarone and its major metabolite desethylamiodarone in human serum has been developed. This method is suitable for pharmacokinetic studies and for monitoring of the drug and metabolite concentrations in serum of patients on both short and long-term therapy with amiodarone.

Ventricular aneurysm is a frequent complication of myocardial infarction, but its diagnostic and prognostic implications are not fully defined. A surgical series of 66 ventricular resections for symptomatic left ventricular aneurysm is analyzed. Pts. age varied between 26-29 years; the interval between the episode of infarction and operation from 2 mos. to 12 years. Indication for surgery was angina in 53% of the cases, heart failure in 23%, arrhythmias in 15%, angina and failure in 9%. In 55 cases surgical findings were consistent with true aneurysm in the anatomical sense, in 11 cases with a wide area of wall akinesia. In 24 cases endocavitary thrombosis was present. In 23 cases aneurysmectomy was the only surgical procedure, with closure of acquired VSD in 1 case and mitral valve prosthesis in 2 cases. In 43 cases aorto-coronary bypass grafting was associated (single bypass in 18, double in 23, triple in 2). Operative technique underwent modifications in time, in relation to the use of local and general hypothermia, of cardioplegia, of early aortic cross-clamping. Surgical mortality was of 7.5% (5 cases); the actuarial courve, including operative mortality, showed survival of 88% at 1 year and of 78% at 5 years interval. Correlation between mortality and clinical symptomatology, hemodynamic data and surgical findings was not statistically significant; a statistically highly significant correlation was found between mortality and operative technique. The results are interpreted and discussed in relation to the diagnostic definition of the problem, to the criteria of indication to surgery and to the operative technique.

During the period 1966-1977, 705 pacemaker implantations with transvenous endocardial electrode and 369 substitutions of generators were carried out, besides 275 operations treating some complications after implantation were required. The most frequent complications were: endocardial electrode dislocation (9.4%), lesion caused by decubitus (7.5%) and infection of subcutaneous pocket (5%), decubitus lesion and infection of the skin caused by the electrode (1.7%), electrode and generator breaking (1.3%), right ventricle perforation caused by the electrode (0.37%). Surgical mortality-rate was 0.18%.

A case of primary ependymoma of the mediastinum is reported. The tumor was adherent to the lung and metastasized to adjacent mediastinal lymph nodes. An autopsy showed no evidence of tumor in the central nervous system. The diagnosis of ependymoma was confirmed by the immunohistochemical positivity for glialfibrillary acidic protein. To the best of our knowledge, this is the first reported example of an ependymoma in this location.

Cefonicid pharmacokinetics in serum and tissue penetration into the lung parenchyma, bronchial mucosa and pleura were studied in 39 patients undergoing lung excision for malignancy. Cefonicid concentrations in serum and tissues samples were assayed at different times after a single 1 g intramuscular administration. The concentrations observed were much higher than the reported minimal inhibitory concentrations for the microorganisms commonly responsible for bronchial and pulmonary infections and therapeutic concentrations were still detectable in the tissues 24 h after dosing. Kinetic findings demonstrated a similar half-life for cefonicid in tissues and in serum. These data provided a further kinetic explanation for the observed clinical efficacy of cefonicid with a single daily dose.

In the last two decades improvements in immunosuppression, surgical technique and graft preservation has impressively enhanced transplantation late results. In the present paper we wonder whether this surgical procedure has a role in the treatment of patients with end-stage respiratory disease as cystic fibrosis (CF). We also try to relate on the main clinical, histological development, present status and the real therapeutic value of cardiopulmonary and double-lung transplantation for end-stage CF. We believe lung transplant may well extend the patient life and give a better quality of life to CF patients who would otherwise die, although functional time is presently unknown. Next years challenge ought to be to go critically through clinical results, to focus on existing problems, together with developing appropriate solutions so to allow a better surgical indication of pulmonary transplantation.

Air-lead levels (PbA) and biological indices were studied in three ceramic factories (185 workers altogether). A difference in the pattern of lead exposure was found in the largest factory (A) and the other two smaller factories (B and C). PbA never exceeded 67 micrograms/m3 in factory A, but reached values as high as 378 micrograms/m3 in factory B. 19% of PbB values were higher than 40 micrograms/100 ml in factory A, 63% in factory B and 35% in factory C. As was expected, a closer analysis of the jobs confirmed a higher exposure level in people directly in contact with lead glazes (glazers and kiln operators). In factories B and C, however, there was also a significant lead uptake in selection and maintenance staff, who worked in areas at some distance from the glazing lines. This may be due in part to pollution spread over all departments, but also to the lack of hygiene and washing facilities whose importance is stressed for effective prevention. Biological monitoring is suggested as being useful for all workers, whatever the lead-air level, bearing in mind the possibility of lead intake orally through soiling.