Biomedical subjects
Publications and source records attributed to C Boutin.
We report a 14 year old boy who presented as a neonate with functional pulmonary atresia due to Uhl's disease with emphasis on the later detection of restrictive right ventricular physiology.
BACKGROUND: The prognosis associated with malignant pleural mesothelioma (MPM) is poor in spite of surgery, radiotherapy, photodynamic therapy, or chemotherapy. Therefore, new therapeutic strategies, including intrapleural immunotherapy, are being investigated. Several clinical studies have demonstrated objective antitumoral responses to intrapleural interleukin-2 (IL-2) administration in the treatment of malignant pleurisy. The maximum tolerated dose, 24 x 10(6) IU/m2/day for 5 days, was determined in a Phase I study. Based on these results, a Phase II study was conducted, in which intrapleural IL-2 (21 x 10(6) IU/m2/day for 5 days) was given to patients with MPM. METHODS: Patients with histologically documented MPM were evaluated for response 36 days after treatment by computed tomography scan and thoracoscopy with biopsies. Toxicity was recorded and graded according to World Health Organization criteria. Survival was calculated from the start of treatment to death according to the Kaplan-Meier method, and the survival of responders and nonresponders was compared using the log rank test. RESULTS: Twenty-two patients entered this study. Of the 22 cases of MPM, 19 were epithelial, 2 were mixed, and 1 was fibrosarcomatous. Three patients had Stage IA disease, 1 had Stage IB, 16 had Stage II, 1 had Stage III, and 1 had Stage IV (Butchart classification). All patients received their planned treatment. No dose reduction or interruption occurred. There were 11 partial responses and 1 complete response. Stable disease occurred in 3 patients and disease progression in 7 patients. The overall median survival time was 18 months; the median survival time of responders differed significantly from that of nonresponders (28 months vs. 8 months, P < 0.01). The 24- and 36-month survival rates for responders were 58% and 41%, respectively. CONCLUSIONS: These results confirm that intrapleural administration of IL-2 is well tolerated and has antitumor activity in patients with MPM. The authors recommend a dose of 21 x 10(6) IU/m2/day for 5 days. However, determination of the schedule of IL-2 and its superiority to conventional treatment in a Phase III study has yet to be accomplished.
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A hospital-based case-control study of the association between past occupational exposure to asbestos and pleural mesothelioma was carried out in five regions of France. Between 1987 and 1993, 405 cases and 387 controls were interviewed. The job histories of these subjects were evaluated by a group of experts for exposure to asbestos fibers according to probability, intensity, and frequency. A cumulative exposure index was calculated as the product of these three parameters and the duration of the exposed job, summed over the entire working life. Among men, the odds ratio increased with the probability of exposure and was 1.2 (95% confidence interval (CI) 0.8-1.9) for possible exposure and 3.6 (95% CI 2.4-5.3) for definite exposure. A dose-response relation was observed with the cumulative exposure index: The odds ratio increased from 1.2 (95% CI 0.8-1.8) for the lowest exposure category to 8.7 (95% CI 4.1-18.5) for the highest. Among women, the odds ratio for possible or definite exposure was 18.8 (95% CI 4.1-86.2). We found a clear dose-response relation between cumulative asbestos exposure and pleural mesothelioma in a population-based case-control study with retrospective assessment of exposure. A significant excess of mesothelioma was observed for levels of cumulative exposure that were probably far below the limits adopted in most industrial countries during the 1980s.
Intrapleural injections of recombinant human IFN-gamma have shown some efficacy in reducing tumor growth in early stages of diffuse malignant mesothelioma (DMM). Here, we have addressed the potential therapeutic effect of IFN-gamma in DMM by investigating the activation of the JAK/STAT signaling pathway in seven human mesothelioma cell lines (HMCLs) that were differentially responsive to the antiproliferative activity of IFN-gamma. We showed that janus kinase 2 (JAK2) and signal transducer and activator of transcription 1 (STAT1) were phosphorylated on tyrosine residues within 15 min in all the HMCLs in which IFN-gamma (500 units/ml) inhibited proliferation. In addition, STAT1 binding activity to the gamma-activated sites DNA sequence was detected within 15 min in electrophoretic mobility-shift assay analysis, and IFN regulatory factor-1 RNA expression was observed within 6 h in the more responsive cells (72.7-95.2% inhibition of DNA synthesis after 72 h of treatment). Conversely, in several HMCLs, absent or limited growth suppressive effect (less than 22% inhibition of DNA synthesis) was associated with alterations in expression or activation of JAK2 or STAT1 or, downstream, with low induction of IFN regulatory factor-1 RNA expression and/or STAT1 protein expression following IFN-gamma treatment. These data suggest that at least part of the IFN-gamma effect on proliferation of HMCLs is mediated directly through activation of the JAK/STAT1 signaling pathway, and it could account for the antitumoral activity reported in DMM patients treated with IFN-gamma.
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BACKGROUND: Cardiac catheterization is commonly performed before repair of ventricular septal defect (VSD) in infancy. No study has addressed the accuracy of echocardiography alone in defining all of the important anatomic features in this population. METHODS: Consecutive infants undergoing VSD repair between 1991 and 1995 (n = 156) were reviewed. The number of additional VSDs and the presence of commonly associated lesions were recorded for each technique and compared with a reference standard consisting of a combination of surgical findings plus postoperative echocardiography and clinical findings. The associated lesions were right ventricular muscle bundles, subaortic ridge, and persistent ductus arteriosus. RESULTS: The sensitivity and specificity of echocardiography in the detection of additional VSDs was 60% and 99% compared with 53% and 97% for cardiac catheterization and 73% and 96% for both techniques. These differences were not statistically significant. No differences were seen in the detection of commonly associated lesions. CONCLUSION: Routine preoperative cardiac catheterization for infants with a primary diagnosis of VSD is probably no longer justified.
We report the successful excision of a large left atrial rhabdomyoma producing complete obstruction of both inflow and outflow to the left ventricle. Systemic perfusion was dependent on anterograde ductual flow. The resultant univentricular physiology was initially managed medically, with spontaneous tumor regression contemplated as a means of possible long-term "cure." Failure to achieve hemodynamic stability compelled urgent surgical excision. This neonate was successfully discharged home with an in-series biventricular circulation.
OBJECTIVES: The purpose of this study was to determine the incidence, risk factors, and outcomes of acquired stenosis of the neopulmonary valve after the neonatal arterial switch operation. METHODS: Reviewed were the preoperative and follow-up echocardiograms from 136 of 288 patients undergoing the arterial switch operation for whom adequate studies were available. Pulmonary stenosis was defined as a thickened and doming pulmonary valve and a pressure gradient of 20 mm Hg or more. Transposition of the great arteries was present with intact ventricular septum in 91 patients, with a ventricular septal detect in 39, with an aortic coarctation in 5, and with double-outlet right ventricle in 1 patient. No patient had preoperative valvular abnormalities (i.e., a bicuspid valve). RESULTS: During a median follow-up of 18 months (range <1 to 90 months), 32 patients (24%) had the development of supravalvular pulmonary stenosis, 15 (11%) with associated pulmonary valve stenosis (group I). Kaplan-Meier estimates of freedom from any intervention were 94% (95% confidence interval, 90% to 99%) at 1 year and 79% (95% confidence interval, 64% to 94%) at 5 years. The valve anulus before the arterial switch operation was significantly larger (p < 0.03) in those in whom neopulmonary valve stenosis did not develop (group II) than it was in those in whom it did (group I). At follow-up, the pulmonary valve anulus had decreased significantly in diameter in group I (p < 0.0005) and had remained larger in group II (p = 0.06) compared with normal diameter. Group I patients had the development of significant pulmonary valve hypoplasia (p < 0.03) whereas group II patients continued to have significantly larger valves compared with normal size (p < 0.0001). CONCLUSIONS: Neopulmonary valve stenosis after the arterial switch operation is not uncommon and is associated with growth failure of the valve anulus often associated with supravalvular pulmonary stenosis.
INTRODUCTION: Our purpose was to assess the efficacy, permanence and safety of thoracoscopic talc poudrage (TTP) for pleurodesis in malignant effusions. We report the follow-up of 360 patients who received TTP in two centers in Marseille (France). CURRENT KNOWLEDGE AND KEY POINTS: Eighty-eight patients presented with mesothelioma and 272 had pleural metastasis. The mean follow-up time was 12 months (range: 2-120). Out of the 327 patients whose response could be evaluated, 90.2% had a successful pleurodesis at 1 month, and 82.1% had a life-long pleural symphysis. Adverse effects included one death 3 days after the procedure in an end-stage patient, fever (9.8%), infection of the parietal scar (2.5%) and pulmonary infection (0.8%). FUTURE PROSPECTS AND PROJECTS: TTP is an effective and safe method of life-long pleurodesis. It should be performed early on in the history of malignant effusions to avoid failures of the technic, mainly linked to trapped lung and to the general condition of patients.
Thoracoscopy provides diagnosis of pleural diseases with a high degree of accuracy. Moreover, this procedure allows a careful pleural staging of the disease, in particular for pleural cancer, which is important for the prognosis and therapeutic decision. This article focuses on the technique, indications, and results of medical thoracoscopy.
Occlusion of the atrial septal defects in the oval fossa by interventional catheterization has progressed, but still has limitations. Three-dimensional (3D) echocardiography can provide unique views unavailable by cross-sectional imaging. The objective of this study was to define the clinical application of 3D echocardiography in the assessment and monitoring of transcatheter occlusion of atrial septal defects. Three-dimensional echocardiography was attempted prior to occlusion of atrial septal defects in 41 patients (median age 8.6 years). Serial cross-sectional images were acquired by multiplane transoesophageal echocardiography and displayed by means of computer reconstruction. Dynamic 3D echocardiographic images of defects in the oval fossa were obtained in 40 of 41 patients (98%). Volume-rendering demonstrated the anterosuperior rim in 36 (90%) and the inferoposterior rim in 24 (60%), but failed to reveal small additional fenestrations in six. Sizes measured by 3D echocardiography were significantly larger than those provided by cross-sectional transoesophageal echocardiography (p=0.007), but differed little from those obtained with balloon sizing (p=0.6). After occlusion, 3D echocardiography showed positions of all arms of the device in 20 of 24 cases. Location of any protruding arms, or residual defects, were also clearly revealed. Three-dimensional images obtained in 12 patients during deployment of the double-umbrella device were useful in monitoring its position (single-frame) and for explaining the mechanism of protrusion. Current 3D echocardiography provides clinically relevant information for selection of patients for closure of atrial septal defects by interventional catheterization and when monitoring during implantation. Information obtained by this technique can clarify the mechanism of deployment of the device and closure of the defect, therefore influencing outcomes.
The authors evaluate the combination of three drugs, vinorelbine, ifosfamide, and cisplatin, which have been shown to produce good response rates and a significant gain in survival when any two of them are given together. Seventy-seven untreated patients with inoperable stage III-IV non-small-cell lung cancer from three centers were included. The combination consisted of cisplatin 30 mg/m2 daily, ifosfamide 1,500 mg/m2 daily, mesna 1,500 mg/m2 daily on days 1-3, and vinorelbine 25 mg/m2 daily on days 1 and 8. Four cycles were administered every 4 weeks for a total of 267 cycles, before an assessment for toxicity, effective dose intensity, response rate, and survival was made. Toxicity was mainly hematologic (grade 3-4 neutropenia (15.7%), anemia (8.2%), and thrombopenia (2.6%)) but did not require granulocyte colony-stimulating factors. Objective response rate was 41.1% (95% confidence interval, 29.5-52.9%) in 68 patients suitable for assessment. The mean time to progression and median survival were 7.7 +/- 1.3 months and 11.6 months, respectively. One-year survival was 47.1%. The effective dose intensity of cisplatin and ifosfamide correlated strongly with survival, whereas stage and performance status did not. This study confirms previously reported favorable results for response and survival rates obtained in stage III-IV non-small-cell lung cancer with the vinorelbine, ifosfamide, and cisplatin combination. Respect of a scheduled dose intensity has a clear-cut influence on survival and should be evaluated routinely in future polychemotherapy trials.
The incidence of malignant pleural mesothelioma (MPM) has risen for some decades and is expected to peak between 2010 and 2020. Up to now, no single treatment has been proven to be effective and death usually occurs within about 12-17 months after diagnosis. Perhaps because of this poor prognosis, early screening has incited little interest. However, certain forms may have a better prognosis when diagnosed early and treated by multimodal therapy or intrapleural immunotherapy. Diagnosis depends foremost on histological analysis of samples obtained by thoracoscopy. This procedure allows the best staging of the pleural cavity with an attempt to detect visceral pleural involvement, which is one of the most important prognostic factors. Although radiotherapy seems necessary and is efficient in preventing the malignant seeding after diagnostic procedures in patients, there has been no randomized phase III study showing the superiority of any treatment compared with another. However, for the early-stage disease (stage I) a logical therapeutic approach seems to be neoadjuvant intrapleural treatment using cytokines. For more advanced disease (stages II and III) resectability should be discussed with the thoracic surgeons and a multimodal treatment combining surgery, radiotherapy and chemotherapy should be proposed for a randomized controlled study. Palliative treatment is indicated for stage IV. In any case, each patient should be enrolled in a clinical trial.
STUDY OBJECTIVE: To determine the effectiveness of pleurodesis by thoracoscopic talc poudrage (TTP) in patients with low pH malignant pleural effusions. DESIGN: Review of prospectively collected data on all thoracoscopic procedures performed from 1982 to 1996. PATIENTS AND SETTING: Twenty-five members in a prepaid, closed-panel health maintenance organization, whose malignant pleural effusion pH was < or = 7.30. INTERVENTIONS: Pleural fluid pH was measured prior to diagnostic and therapeutic, single puncture, rigid thoracoscopy, under local anesthesia, in an operating room. MEASUREMENTS AND RESULTS: Success of pleurodesis was determined with serial radiographs at 10 days, 30 days, and frequent intervals until death or up to 1 year following the procedure. Failure was indicated by evidence of recurrent fluid or persistence of a space between the visceral and parietal pleura. Morbidity of the procedure, days of chest tube drainage, and days of hospitalization were recorded concurrently during hospitalization and outpatient follow-up. Fifty of the 76 patients found to have a pleural pH measurement had a pleural pH >7.30, averaging 7.37 (7.31 to 7.55). The other 26 patients (34%) with pH < or = 7.30 (low pH) are the subjects of this study, of whom 25 were evaluable. Pleurodesis was successful in 22 of 25 (88%), although 4 died prior to 30 days. The three failures all had trapped lung. Chest tube drainage averaged 3.2+/-1.3 days, which approximated the time of hospitalization (3.3+/-1.1 days). There were no thoracoscopy-related deaths; significant morbidity occurred only in one patient with trapped lung, who had prolonged chest tube drainage before and after TTP, and eventually developed empyema. CONCLUSIONS: TTP is an effective pleurodesis technique in malignant pleural effusions, even when the pleural pH is low. The short hospital stay and high success rate make this approach a good choice in palliating symptomatic malignant pleural effusions.
Some recent data on malignant pleural mesothelioma are reviewed, viz. the French 1996 INSERM report, our mineralogic study of anthracotic parietal pleura, and the new TNM classification of the International Mesothelioma interest Group (I.M.I.G.). Among medical treatments, intrapleural immunotherapy achieves the best objective responses in early stage mesothelioma. Radiotherapy alone has little effect on advanced mesothelioma. By contrast, recent surgical series have shown better survival rates and underline the interest of the new TNM staging. Finally, malignant pleural mesothelioma behaves something like lung cancer, in that only in N- stages can prolonged survivals be expected.
In over 90% of cases, mesothelioma initially presents as a banal pleural effusion, contributing no orientation to the diagnosis. The pleural fluid can even disappear after initial puncture. For early diagnosis, simple puncture, with or without biopsy, does not suffice. Thoracoscopy is 98% diagnostic. The course depends on the stage, the histological type and the general status. A new international TNM classification has been proposed to allow comparison of series and to choose a treatment appropriate to the stade: at stage I, intrapleural, local immuno-chemotherapy treatment gives good results; at stages II and III, surgery followed by radiation therapy are indicated; at stage IV, symptomatic treatment alone is justified.
PURPOSE: Heart rate is considered to be a major determinant of cardiac output in infants and small children but the relationships between age, heart rate and cardiac output in humans have never been clearly established. This study was designed to determine the change in cardiac output following atropine iv to anaesthetised infants and small children. METHODS: Following Institutional Ethics Committee approval and written-informed consent, 20 ASA I or II unpremedicated patients aged from 1 to 36 mo were studied. Anaesthesia was induced with 5 mg.kg-1 thiopentone, 2 micrograms.kg-1 fentanyl and maintained with halothane 0.5% in nitrous oxide 66% in oxygen. Vecuronium 0.1 mg.kg-1 was used to provide muscular relaxation. Cardiac output was measured by non-invasive transthoracic blind continuous-wave Doppler echocardiography before and after the administration of 0.02 mg.kg-1 atropine iv. RESULTS: Atropine increased both heart rate and cardiac index by 31.1 +/- 12.8% and 29.4 +/- 17.3% respectively (P < 0.05). The cardiac index before atropine was 5.1 +/- 1.2 L.min-1.m-2 and the increase after atropine varied widely from 1.4 to 52.1%. Although atropine did not alter the overall stroke index the recorded changes ranged from -20.8 to +18.0%. There was no association between age and either cardiac index or % change in cardiac index after atropine. However, there was a positive but weak correlation between percentage change in heart rate and cardiac output (r2 = 0.46). CONCLUSION: Atropine causes a variable increase in cardiac output in infants and children aged between 1 and 36 mo. The change in cardiac output, considering the limits of the transthoracic echocardiography methodology, suggests that this is related to the increase in heart rate but is not dependent of age.