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Biomedical subjects

J Brune

Publications and source records attributed to J Brune.

At least 19 recordsLinked to original sources

Vaccination with a recombinant vaccinia vaccine containing the B7-1 co-stimulatory molecule causes no significant toxicity and enhances T cell-mediated cytotoxicity.

B7-1 is a co-stimulatory molecule that provides a second signal for T-cell activation. Several studies have demonstrated that vaccination with a vector containing genes encoding B7-1 and an antigen appears to be efficacious at promoting immune responsiveness to the antigen. To evaluate the safety of such a protocol and determine the effect of the B7-1 vector on immune responsiveness, female C57BL/6 mice were administered Wyeth wild-type vaccinia virus (V-WT) or V-WT containing the gene for B7-1 (rV-B7-1) as a single s. c. injection or 3 monthly s.c. injections. Immunologic parameters were evaluated in half of the mice and general toxicity in the other half. Immunologic end points included determination of splenic lymphocyte phenotypes, mitogen-induced T- and B-cell proliferation, T-cell proliferation in response to alloantigens, cell-mediated cytotoxicity (CMC), natural killer cell activity and serum anti-nuclear antibody (ANA) titers. No significant signs of general toxicity were noted. The primary immunologic effect was an increase in the ability of spleen cells to lyse allogeneic targets and to proliferate in response to allogeneic stimulation. Numbers of splenic CD8(+) cells were also increased. These effects were more pronounced after 3 vaccinations than after a single vaccination. Minimal differences in ANA were observed between mice immunized with V-WT and rV-B7-1. In addition, no serum antibodies against B7-1 were detected in any mice. The data suggest that vaccination with rV-B7-1 augments CMC with minimal toxicity.

Alanine Transaminase↗

Small-cell lung cancer: patients included in clinical trials are not representative of the patient population as a whole.

PURPOSE: To determine the clinical characteristics of the subpopulation of patients not included in clinical trials, their outcome, and the reasons for their ineligibility and non-participation. PATIENTS AND METHODS: We studied 57 patients (out of 178 consecutive patients with SCLC), who were not included in any of the three successive clinical trials completed at our center during the study period. We also compared 37 patients excluded from the largest clinical trial to their 73 included counterparts. RESULTS: Reasons for ineligibility (n = 53) included low Karnofsky index (n = 17), advanced age (n = 12), non-feasible long-term follow-up (n = 12), previous history of cancer (n = 8), contraindication for anthracyclines (n = 5), and other medical reasons (n = 11). Only four eligible patients were not included in the trials. As compared to patients included in the studies, non-included patients had a significantly lower Karnofsky index, were older, presented more frequently with metastatic disease, and had a lower response rate to treatment and a shorter survival. However, exclusion from the trial was not an independent prognostic factor by multivariate analysis. CONCLUSIONS: Selection biases were unlikely in the three trials, based on the high ratio of included/eligible patients. However, the subgroup of patients included in the trials was not representative of the patient population as a whole because of restrictive eligibility criteria. Results from published clinical trials to the overall population should be extrapolated only with caution. We suggest that the proportion and major characteristics of ineligible and non-participating patients be mentioned in any publication of a clinical trial.

Adult↗

[Pleuro-peritoneal Denver shunt in treatment of chronic pleurisy].

The first utilisation in our hospital of a pleuraperitoneal shunt for the treatment of chronic pleurisy enabled us to study, in the light of published data, the place for such a procedure in the management of resistant pleural effusion. The aetiology of the pleurisy in a 70-year old patient who underwent this mini-invasive surgery was unknown when the shunt was inserted, but his symtoms clearly improved afterwards. At the present time with a follow-up of 13 months, there are no local complications and the system is in good working order. In 1982, the material used for the first time in such a case was an adapted version of Denver's peritoneal venous shunt. This is composed of a pleural catheter linked by a pump that the patient controls himself, to a peritoneal catheter. This pump can be inserted under local anaesthetic. The principal indications in the literature, in which the series do not exceed 70 cases are: malignant pleurisy where it is preferable to introducing tale in the case of tissue retraction fastening to the underlying lung and also in chylous pleurisy, especially those secondary to congenital east disease in children. A complication rate of 25% is noted depending on the type of infection or obstruction leading to replacement of the shunt. No case of erosion has been noted. The long term patency, measured by radio-isotope injections (Tc99m), has not been studied but there is a significant reduction in the length of hospital stay which gives a clear economic advantage to such procedures.

Aged↗

[Tracheal stenosis of inflammatory aspect].

We report a case of tracheal leishmaniasis with stenosis in a 52 year-old female originative from the Gard region (South of France). The unusual localization acknowledges for the difficulties met in setting the diagnosis which was established through cytological examination of bronchial brushing. Though rare, leishmaniasis infection must be suspected in all cases of mucosal lesions occurring in patients living in endemic areas.

Bronchoscopy↗

Clinical and radiological aspects of Villaret's syndrome.

A 68-year-old man with a history of large cell lung carcinoma presented 1 year after surgical management of the initial lesion, with a complete unilateral IX-XII cranial nerve palsy with Horner's sign. This rare multiple cranial nerve palsy is called Villaret's syndrome. It suggests an extracranial lesion located in the retroparotid space. Complete basal skull radiology work up including computed tomography and magnetic resonance imaging confirmed the location of the causal lesion in the retroparotid space.

Aged↗

A phase II trial of fotemustine and cisplatin in central nervous system metastases from non-small cell lung cancer.

A phase II study was conducted in order to determine the feasibility and toxicity of cisplatin combined with the nitrosourea fotemustine in central nervous system metastases from non-small cell lung cancer. 31 chemotherapy-naïve patients were included between November 1990 and April 1993. Computed tomography scan-documented tumour regression in brain metastases was observed in 7 of the 25 evaluable patients, but only 4 of these (16%) lasted more than 4 weeks. In 2 of these 4 patients, the response on central nervous system metastases was considered as complete. The median duration of response was 20.5 weeks and the median survival was 16 weeks overall and 28.5 weeks for responding patients. The limiting toxicity of this regimen was haematological. 2 patients died from infectious pneumonitis while in neutropenia. Treatment delays due to haematological toxicity occurred in 57% of patients. Despite the rather encouraging response rate, such toxicity appears too high when compared to the overall bad prognosis of this population of patients. Cranial radiotherapy remains the standard treatment in this setting and should only be compared in the future to less aggressive schedules.

Adult↗

Thin-section CT detection of emphysema associated with bronchiectasis and correlation with pulmonary function tests.

PURPOSE: To evaluate, on thin-section CT scans, the prevalence of emphysema in patients with bronchiectasis and to correlate the results of thin-section CT scans with the results of pulmonary function tests, in order to question whether there was a particular functional test profile in this group of patients. PATIENTS AND METHODS: This is a retrospective study including 90 patients having both thin-section CT scans and pulmonary function tests for bronchiectasis. A CT scoring system was established for assessing the airway disease by the severity and extent of bronchiectasis and by the extent of emphysema. CT scans were reviewed independently by two reviewers and final interpretation was obtained by consensus. Results of thin-section CT scans were correlated with results of pulmonary function tests, including FEV1 and FEV1/FVC to assess air-way obstruction, total lung capacity and residual volume to assess air trapping, and diffusing capacity for carbon monoxide/alveolar volume (DCO/VA). RESULTS: CT evidence of emphysema, which was noted in 45% of the patients (n = 41), was mainly localized in the same bronchopulmonary segments as bronchiectasis. The presence of emphysema was in relation to the extent and to the severity of bronchiectasis. Only eight patients with CT evidence of emphysema had functional evidence of emphysema (20%). When comparing the group of patients with CT evidence of emphysema with the group of patients with no CT evidence of emphysema, the group of patients with CT evidence of emphysema had significantly higher airflow obstruction and air trapping, had significantly lesser value of diffusing capacity, but with no decreased gas transfer (DCO/VA > 80%). CONCLUSION: Our series suggests that there is a high prevalence of emphysema in patients with bronchiectasis. Emphysema that was not suggested using pulmonary function tests in most of the cases could explain in part the higher airway obstruction observed in the group of patients with CT evidence of emphysema. This study could support the suggestive notion that emphysema, which was mainly localized in bronchiectatic lobes, could be due to the inflammatory airway process.

Bronchiectasis↗

[Lung transplantation in COPD].

Pulmonary transplantation can be performed as a treatment for panlobular emphysema. Young patients can benefit from pulmonary transplantation: double lung transplantation for patients aged less than 55 years and single lung transplantation for patients aged less than 60 years. Only patients with major functional impairment should be considered for transplantation. It is assessed by pulmonary function tests, but also by evaluating the intensity of dyspnea and the decreased quality of life. In emphysema, transplantation is the treatment of the respiratory handicap without decreased life expectancy. The results of pulmonary transplantation in emphysema are similar to that of other indications. Mean actuarial survival is 65% at one year, and 40% at four years. Quality of the survival should be considered in assessing the results of pulmonary transplantation. It is estimated that 50% of the surviving patients have a satisfactory improvement in the quality of life.

Contraindications↗

Post-transplant obstructive lung disease ("bronchiolitis obliterans"): a clinical comparative study of bone marrow and lung transplant patients.

Patients at a single pulmonary centre who developed obstructive lung disease after bone marrow transplantation (BMT) and lung transplantation (LT) were studied, in order to compare the clinical expression of post-transplant obstructive lung disease (PTOLD) (bronchiolitis obliterans) in these two conditions, which have so far been studied separately. Nine out of 179 patients surviving more than 100 days after BMT (5%) and 9 out of 44 patients surviving more than 100 days after LT (20%) developed post-transplant obstructive lung disease. This was defined by an irreversible airflow obstruction, as characterized by a forced expiratory volume in one second divided by forced vital capacity (FEV1/FVC) of less than 70%, and a FEV1 of less than 70% of predicted value. The mean interval between transplantation and the diagnosis of post-transplant obstructive lung disease was 262 days and 217 days for BMT and LT patients, respectively. In all cases, pulmonary symptoms consisted of dyspnoea and progressively productive cough. Bronchial dilatation on high-resolution computed tomography scans was the main imaging feature present in both groups of patients at the onset of post-transplant obstructive lung disease. The mean FEV1/FVC ratio was 51 and 54% for BMT and LT patients, respectively. All BMT and LT patients had normal transfer coefficient. Clinical chronic graft-versus-host disease was present in all BMT patients before or concurrent with the onset of post-transplant obstructive lung disease, and all LT patients had presented at least one episode of acute lung rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Delayed detection of cystic fibrosis in a patient with Mycobacterium avium complex infection].

We report a case of pulmonary infection by Mycobacterium avium complex revealing in a 21 years old patient a cystic fibrosis heterozygous for the delta F 508 deletion. The role of this bacteria in the lung infection is suggested by repeated isolation. This infection caused bronchitis, hypoxemia and pulmonary nodules at CT scan. The clinical and radiological signs improved after treatment with four antibiotics whereas only clarithromycin showed in vitro activity. An obstructive disease due to allergic bronchopulmonary aspergillosis developed and was controlled by steroid therapy.

Adult↗

[Cutaneous Kaposi's sarcoma with pulmonary carcinomatous lymphangitis in patient with heart transplantation].

The great strides in organ transplantation have been accompanied by some specific pathologies, notably, neoplasia, including Kaposi's sarcoma which occupies the third place in frequency after cutaneous tumours and malignant lymphomas. We report a case of cutaneous Kaposi's sarcoma developing some six months after a cardiac transplant. The modulation of immuno-suppression and treatment with Alpha interferon allowed an initial stabilisation of the cutaneous lesions. However, there were secondary developments of the lesions and, 21 months after the initial presentation, the patient developed a diffuse infiltrating pneumonia leading to death. The autopsy revealed lymphangitis carcinomatosis of Kaposi's sarcoma type. This observation underlines the therapeutic difficulties seen in Kaposi's sarcoma after organ transplantation when there is no alternative to allow a significant reduction or cessation of immuno-suppression.

Carcinoma↗

[Acute eosinophilic lung after a course of minocycline].

Acute pulmonary eosinophilia was observed in the patient after taking minocycline. The clinical picture recurred when the drug was re-introduced. However, this is a rare complication after taking a derivative of tetracycline. An eosinophilia was seen in the peripheral blood and also in the bronchoalveolar lavage. Cessation of the drug therapy without the addition of corticosteroids allowed a cure.

Acne Vulgaris↗

Optimal delivery of dose in cancer chemotherapy with the support of haematopoietic growth factors.

The delivery of cancer chemotherapy is often non-optimal because of dose reductions and delays related to various toxic effects. These result in a decrease of the dose intensity as well as of the relative dose intensity of a given regimen compared to a reference protocol. In retrospective studies, such modifications have been shown to negatively influence the therapeutic results in many clinical situations. The ability of haematopoietic growth factors to reduce chemotherapy-related neutropenia and its associated infectious complications allows better dose-on-time delivery of the chemotherapeutic drugs. The potential therapeutic impact of this effect remains to be determined in prospective studies.

Antineoplastic Combined Chemotherapy Protocols↗

[Treatment of epithelial tumors of the thymus gland].

Epithelial thymomas are a rare type of malignant tumors. The treatment is based on surgical excision especially in non invasive tumors where no other treatment is recommended. In totally or partially unresectable tumors, surgery remains of major importance in tumor debulking, staging, and histological typing. Improvement of radiotherapy techniques allow to optimise the combination of radiation therapy with surgery and/or chemotherapy and to decrease the pulmonary and cardiac secondary effects. The effectiveness of chemotherapy has long been reported case to case. Recently published prospective studies have confirmed the efficacy of anthracyclines and cisplatinum combination regimen and demonstrated the need for further trials using neo-adjuvant chemotherapy. Such studies on a rare and slowly growing tumor have to be proposed in a prospective, multicentric and controlled manner.

Antineoplastic Combined Chemotherapy Protocols↗

[Value of C-reactive protein determination in small cell lung cancer].

A prospective analysis of serum levels of C-reactive protein (CRP) has been conducted on a series of 39 small cell lung cancer (SCLC) patients during the first course of chemotherapy in order to evaluate the predictive value of this marker on tumoral extension at diagnosis and response to therapy. Serum levels of CRP were measured before chemotherapy (day 0) and during the first two days of treatment (day 1, day 2). Twenty-three of 32 evaluable patients (71%) had extensive disease. The mean pre-treatment CRP level was significantly higher in this group than in the group of patients with limited disease (52.3 mg/l vs 15.8 mg/l, P = 0.02). Twenty-three patients responded to treatment and nine did not. The evolution of serum CRP levels in both groups was compared between day 0 and day 2. A more than two-fold increase of initial CRP levels showed a 100% predictive value for response. On the other hand, a decrease by more than 50% of initial serum levels was associated with a negative predictive value of 75% for response. We conclude that the follow-up of CRP levels during initial chemotherapy of SCLC might be useful in the initial evaluation of tumoral extension and in the early prediction of response to therapy.

Antineoplastic Combined Chemotherapy Protocols↗