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Biomedical subjects

E Russi

Publications and source records attributed to E Russi.

At least 19 recordsLinked to original sources

Best supportive care in non-small cell lung cancer: is there a role for radiotherapy and chemotherapy?

Best Supportive Care (BSC) is the treatment of choice when cure is not achievable with anticancer treatments and involves management of disease-related symptoms. In the palliative treatment of non-small cell lung cancer (NSCLC) radiation therapy has for a long time been the cornerstone of symptom management, although the best schedule is still to be defined. Chemotherapy, on the other hand, has been excluded from classical definitions of BSC and has been reserved only for selected patient populations in which a survival benefit was demonstrated using cisplatin-based regimens. We reviewed randomized trials on both palliative radiotherapy and chemotherapy in order to assess the impact of anticancer treatments on quality of life in advanced NSCLC patients. While no randomized trials compared radiation therapy with a control arm not including it, several randomized trials assessed the use of different schedules. Hypofractionated schedules seem to have comparable palliative activity when compared with the standard fractionated regimens, at least in metastatic, poor-prognosis patients. In locally advanced, inoperable NSCLC higher radiation doses administered with conventional fractionation achieve better results in terms of local control and survival. The rate of palliation of local symptoms is high, being 60-80% for chest pain and hemoptysis, while breathlessness and cough are controlled at a somewhat lower rate (50-70%). General symptoms (fatigue, anorexia, and depression) are affected in a minority of patients. Chemotherapy was compared with BSC in several randomized trials, in some of which an analysis of the quality of life was included. Results are consistent in favor of its palliative role and, when local symptom control is assessed, rates of palliation seem similar to those achieved by radiation. Benefits apply to metastatic NSCLC patients with good performance status, low body weight loss, age below 70-75. However, some studies support the use of chemotherapy also in patients with poor prognostic features. A comparison in terms of quality of life and symptom palliation between different chemotherapy regimens is the object of few trials. Both chemotherapy and radiation have an important role in the palliative treatment of advanced NSCLC patients and should be included in BSC programs. Future randomized trials should assess the best way of combining these two approaches.

Adult↗

Microembolic signal counts increase during hyperbaric exposure in patients with prosthetic heart valves.

BACKGROUND: Patients with prosthetic heart valves have an increased risk of thromboembolic events, and transcranial Doppler sonography reveals microembolic signals. Whereas microembolic signals were initially assumed to be of particulate matter, recent studies suggest that they are partially gaseous in origin. If this is true, alteration of environmental pressure should change microembolic signal counts. We undertook this study to evaluate the influence of hyperbaric exposure on microembolic signal counts in persons with prosthetic heart valves. METHODS AND RESULTS: Microembolic signal counts were monitored by transcranial Doppler sonography of both middle cerebral arteries under normobaria (normobaria 1), 2 subsequent periods of hyperbaria (2.5 and 1.75 bar), and a second period of normobaria (normobaria 2) in 15 patients with prosthetic heart valves. Each monitoring period lasted 30 minutes. Compression and decompression rates were 0.1 bar/min. Microembolic signal counts increased from 20 (12-78) at normobaria 1 to 79 (30-165) at 2.5 bar (P <.01 vs normobaria 1 and 2), decreased to 44 (18-128) at 1.75 bar (P <.01 vs normobaria 1 and 2.5 bar; P <.001 vs normobaria 2), and returned to 20 (8-96) at normobaria 2 (values are medians and 95% confidence intervals). CONCLUSIONS: Our results strongly suggest that gaseous bubbles are underlying material for part of the microembolic signals detected in patients with prosthetic heart valves.

Aortic Valve↗

Interleukin-10 secretion by alveolar macrophages and monocytes in sarcoidosis.

BACKGROUND: Alveolitis and the production of proinflammatory cytokines are known features of sarcoidosis. Because of the usually spontaneous resolution of alveolitis despite local secretion of mediators causing inflammation and granuloma formation, we hypothesized that downmodulating mechanisms such as anti-inflammatory cytokines might be involved in this process. OBJECTIVE: Investigation of the secretion of the macrophage deactivating cytokines interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) by alveolar macrophages in untreated sarcoidosis of the lung. METHODS: Fourteen consecutive and untreated patients with pulmonary sarcoidosis and 18 volunteers underwent bronchoscopy. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage and the secretion of IL-10 and TGF-beta was studied. RESULTS: Spontaneous IL-10 production by AM was found in 6 of 14 patients and in 2 of 18 controls. The IL-10 level of lipopolysaccharide-stimulated AM was significantly higher in patients. Monocytes secreted significantly more IL-10 than AM, but there was no difference between sarcoid and control monocytes. No difference was found in the secretion of TGF-beta between patients and controls. CONCLUSION: Increased local secretion of IL-10 - but not TGF-beta - may represent a downmodulating mechanism involved in the spontaneous resolution of alveolitis in sarcoidosis.

Adult↗

Management 1997 of chronic obstructive pulmonary disease. Working Group of the Swiss Society of Pneumology.

COPD is a disorder characterized by expiratory flow limitation that does not change markedly over periods of several months' observation. When the diagnosis is suspected, COPD patients should be submitted to full assessment and initiation of therapy. Initial assessment includes a complete history, a detailed physical examination, pulmonary function tests, a chest X-ray, and blood tests. Therapy of COPD aims at reducing symptoms, preventing exacerbations and preserving optimal lung function. Many COPD patients have a bronchospastic component and usually show some response to bronchodilator therapy. Anticholinergics, beta 2-agonists or theophylline are used as monotherapy or in combination. A subgroup of patients with COPD may benefit from oral long-term corticosteroid therapy. At prime diagnosis of COPD, a trial of oral steroid under optimal bronchodilator therapy is warranted in order to identify steroid responders early in the course of the disease. Stopping smoking is the most effective preventive measure and should be combined with complementary approaches such as eviction of environmental irritants, vaccines and prescription of antioxidants. Long-term oxygen therapy is beneficial in chronically hypoxemic patients. Respiratory rehabilitation uses a multidisciplinary approach aiming at decreasing dyspnea, increasing exercise tolerance and improving quality of life. Nocturnal home noninvasive mechanical ventilatory assistance can improve arterial blood gas tensions in patients with respiratory failure, but the long-term effect on survival is still under investigation. In selected patients, surgery (bullectomy, lung volume reduction, lung transplantation) may greatly improve pulmonary function.

Adrenal Cortex Hormones↗

Changes in arterial and transcutaneous oxygen and carbon dioxide tensions during and after voluntary hyperventilation.

The purposes of our study were (1) to investigate whether a 3-min short-term hyperventilation leads to posthyperventilatory hypoxemia and (2) to assess the role of transcutaneous blood gas measurements for monitoring oxygen and carbon dioxide changes during the after the test. In 10 male volunteers arterial and transcutaneous blood gases were measured simultaneously before, during and after a 3-min voluntary hyperventilation maneuver. Baseline arterial PO2 increased from 13.7 +/- 0.4 kPa (103 +/- 3 mm Hg) to 18.6 +/- 0.3 kPa (139 +/- 2.3 mm Hg; p < 0.005 compared to baseline) during hyperventilation. After the provocation test posthyperventilatory hypoxemia occurred with a minimal mean value of 7.8 +/- 1.3 kPa (58.5 +/- 9.8 mm Hg; p < 0.05 compared to baseline). Whereas close agreement between arterial and transcutaneous measurements was obtained for carbon dioxide values before hyperventilation, transcutaneous O2 consistently underestimated arterial O2. A short-term over-breathing of 3 min causes a significant posthyperventilatory hypoxemia. We hypothesize that posthyperventilatory hypoxemia is caused by hypopnea as a result of depleted CO2 body stores. Noninvasive transcutaneous blood gas measurements are not reliable for monitoring blood gas changes during and after hyperventilation, most probably because of the slow response time of the electrodes and the reflex vasoconstriction of the skin vessels.

Adult↗

Prone postioning and low-volume pressure-limited ventilation improve survival in patients with severe ARDS.

STUDY OBJECTIVES: Investigating the effect of low-volume pressure-limited ventilation and repeated prone positioning on the short-term course and outcome in patients with severe ARDS. SETTING: Level 1 trauma center of a university hospital. PATIENTS: Twenty-five patients suffering from ARDS with a lung injury score (LIS) > or = 2.5 admitted consecutively to our ICU from January 1992 to December 1994. METHODS: Mechanical ventilation with peak inspiratory pressure limitation to 35 mbar, irrespective of hypercapnia and prone positioning to achieve adequate oxygenation. SCORING AND MEASUREMENTS: Patient assessment with LIS, APACHE (acute physiology and chronic health evaluation) II score, injury severity score, and multiple organ failure score. Blood gas analyses and estimation of static compliance were repeated at least every 4 h during the treatment period. PaO2/FIO2 (fraction of inspired oxygen) ratio, alveolo-arterial oxygen difference, and intrapulmonary shunt were calculated according to standard equations. The best values taken from each 4-h period during the investigation were used to evaluate the best possible performance of the lung within this interval and to investigate the entire course. RESULTS: Mean predicted mortality based on the APACHE II score was 35.4+/-15.2%. Three of the 25 patients (12%) died. However, none was related to respiratory failure. No pneumothorax occurred. Sixteen patients, lacking any contraindication for prone positioning, responded positively to this change in position, each to a different individual degree. CONCLUSION: We assume that our low mortality in patients with severe ARDS might be due mainly to low-volume pressure-limited ventilation and prone positioning. This simple strategy seems to allow successful treatment for patients with severe ARDS.

APACHE↗

Apoptosis in human alveolar macrophages is induced by endotoxin and is modulated by cytokines.

A central factor in the pathogenesis of inflammatory and fibrotic lung disease (adult respiratory distress syndrome, sarcoidosis, idiopathic pulmonary fibrosis) is the locally elevated number of alveolar macrophages (AM). An elevation in the production rate of AM, chemoattraction and differentiation of monocytes, or a diminution in the death rate might be underlying mechanisms. The aim of the present study was to investigate the modulatory role of endotoxin and cytokines on the death rate of human AM. Lipopolysaccharide (LPS) treatment resulted in a 4-fold increase (7.6 to 30.2%) of AM death. AM death was apoptotic as assessed by in situ DNA end labeling (ISDE), transmission electron microscopy, DNA gel electrophoresis, fluorometry of fragmented DNA, and an ELISA specific for histone-associated DNA fragments. Among the different bacterial cell wall components tested, LPS was the only inducer of apoptosis in human AM. None of the tested cytokines (interleukin-1 beta [IL-1 beta], IL-4, IL-6, IL-10, tumor necrosis factor-alpha [TNF-alpha], transforming growth factor-beta 2 [TGF-beta 2], interferon-gamma [IFN-gamma], macrophage colony-stimulating factor [M-CSF], granulocyte colony-stimulating factor [G-CSF], and granulocyte-macrophage colony-stimulating factor [GM-CSF]) was capable of enhancing the spontaneous rate of apoptosis. However, LPS-induced apoptosis was significantly enhanced by the macrophage-activating cytokine IFN-gamma, and reduced by the macrophage-deactivating cytokines IL-4, IL-10, and TGF-beta.

Apoptosis↗

GM-CSF-induced acute eosinophilic pneumonia.

There is increasing evidence that haemopoietic growth factors are effective in reversal of neutropenia associated with large granular lymphocytes (LGLs) proliferation. A 19-year-old woman with CD3+/TCR gamma delta+, CD4-, CD8- LGL proliferation and severe neutropenia repeatedly developed blood eosinophilia, fever and dyspnoea after administration of GM-CSF. Acute eosinophilic pneumonia with a lobar lung infiltrate pleural effusion, and marked bronchoalveolar lavage fluid eosinophilia was diagnosed. Treatment with corticosteroids and discontinuation of GM-CSF lead to rapid improvement. In addition, haematological analysis revealed that H*1 Technicon, a widely-used automated cell counter, may misinterpret eosinophils erroneously as neutrophils, therefore examination of blood smears to prevent eosinophil-mediated toxicity during GM-CSF treatment is recommended.

Acute Disease↗

[Simultaneous measurement of arterial and end-expiratory carbon dioxide before, during and after voluntary hyperventilation].

Hyperventilation syndrome is considered an established diagnosis if it is confirmed that the patient's complaints correlate with arterial hypocapnia. In the diagnostic criteria set up by a group in Nijmegen, paCO2 is determined indirectly by measuring the end tidal CO2. Values below 4 kPa measured at rest and 10 or more minutes after deliberate hyperventilation are classified positive diagnostic criteria for hyperventilation syndrome. However, it has not been proven that end tidal pCO2 agrees well with paCO2 during the entire manoeuvre. We performed simultaneous measurements of both parameters in 10 healthy non-smokers, before, during and after 3 minutes of deliberate hyperventilation. A comparison of the values employed for diagnosing a hyperventilation syndrome (during normal respiration before and 10 and more minutes after hyperventilation) yields a mean difference of 0.39 kPa according to the statistical computation described by Bland and Altman (limits of the range of agreement between 0.98 and -0.18). The end tidal CO2 values measured during the normal respiratory phase as well as 10 and more minutes after hyperventilation, agree well with the arterial values (the arterial values being slightly higher). During and shortly after hyperventilation the values obtained by both methods differ from one another, so that the exact degree of hypocapnia during a hyperventilation period cannot be assessed by measuring the end tidal CO2.

Adult↗

[Treatment of superior vena cava syndrome by metal stents. Preliminary experience].

This study was aimed at verifying the feasibility of stent placement in superior vena cava syndrome (SVCS). From April, 1993, to February 1995, fifteen patients (12 men, 3 women, age range: 48-72 years, average age: 58 years), were treated for malignant stenoses involving superior vena cava in 9 cases, right innominate vein in 3, left innominate vein in 2 and subclavian veins in 1. All patients had been submitted to CT angiography and digital venography to assess side, length and type of the stenosis. In 6 patients locoregional fibrinolysis (with urokinase) was performed. The stenosis was successfully dilated by balloon catheter and the stent was finally removed. Subclavian and innominate veins stenoses were treated with Wallstent, using brachial approach, while stenoses of superior vena cava required transfemoral catheterization for Gianturco-Rosch "Z" stent placement. A control venogram was performed after stenting, with the evaluation of pre/post stent pressure gradient, and later at 1, 3 and 6 months. The stents were positioned in all patients with immediate technical success; no major complications occurred. Two recurrences were successfully resolved. Radiation and/or medical therapy without vascular disobstruction showed worse results in the treatment of superior vena cava syndrome. The percutaneous placement of self-expandable stents should be not only the therapeutic alternative to surgery but the method of choice in these pathologic conditions.

Aged↗

Progressive perturbations in cerebral energy metabolism after experimental whole-brain radiation in the therapeutic range.

Basic mechanisms underlying the tolerance and reaction of the central nervous system to ionizing radiation have not been fully elucidated in the literature. The authors employed the [14C]-2-deoxy-D-glucose autoradiography method to investigate the effect of whole-brain x-irradiation on local cerebral glucose utilization in the rat brain. The animals were exposed to conventional fractionation (200 +/- 4 cGy/day, 5 days/week for a total dose of 4000 cGy), and the effects of this regimen were assessed at 2 weeks and 3 months postirradiation. In rats evaluated 2 weeks after treatment, statistically significant decreases in cerebral metabolic activity were found in 13 of the 27 regions studied, compared to control animals. In rats studied 3 months after treatment, additional metabolic suppression and statistically significant decreases in cerebral metabolic activity were found in 11 of the 27 regions, compared to rats studied 2 weeks after treatment. A weighted-average rate for the brain as a whole was approximately 15% and approximately 25% below that of control animals 2 weeks and 3 months after exposure, respectively. Although the difference in species is significant enough so that direct extrapolation to humans may not be appropriate, the data reported here may have potential clinical implications for the evaluation of the risk-benefit ratio for radiotherapy. This model can be used reproducibly for further investigations, including evaluation of therapies that may reduce irradiation-induced brain injury.

Animals↗

[Bronchiolitis obliterans organizing pneumonia (BOOP)--chronic organized pneumonia (COP). Diagnosis, therapy and course].

Cryptogenic organizing pneumonia (COP) or bronchiolitis obliterans organizing pneumonia (BOOP) designates a disease characterized by particular histopathological features. Symptoms and clinical findings are more or less typical and the etiology of the disease is unknown in most of the cases. We report on 7 patients in whom the diagnosis was established by open lung biopsy during a workup for persistent pulmonary infiltrates. The clinical findings, the radiological features and the course during treatment with corticosteroids are analyzed. In all patients the symptoms improved. In two cases we observed relapses after discontinuing the corticosteroids or diminishing the dose. These relapses again responded to steroids, but in one patient progressive pulmonary restriction was noticed despite continuous treatment.

Biopsy↗

[Scuba diving: barotrauma, decompression sickness, pulmonary contra-indications].

The practice of scuba diving is associated with two specific medical problems: barotrauma directly related to changes in ambient pressure, and decompression sickness related to the uptake and the release of inert gases by the body. Neurological symptoms are frequent in severe diving accidents. They may arise following either barotrauma or decompression sickness, and often require urgent treatment in a hyperbaric chamber. Asthma, chronic obstructive pulmonary disease, and spontaneous pneumothorax increase the risk of lung barotrauma and represent contraindications to diving.

Asthma↗

Pulmonary hemorrhage due to inhalation of vapor containing pyromellitic dianhydride.

Pulmonary hemorrhage due to inhalation of fumes or powders containing trimellitic anhydride (TMA) is well known. We report pulmonary hemorrhage in a young man exposed to epoxy resin vapor containing pyromellitic dianhydride (PMDA). Serum IgG antibodies to PMDA could be detected. We conclude that the pulmonary hemorrhage was mediated by a reaction to PMDA in analogy to the TMA-induced disease. We suggest that exposure to any acid anhydride should be considered a possible cause of pulmonary hemorrhage since these compounds share structural and functional similarities.

Adolescent↗

[Sleep apnea].

Regular and unobstructed breathing during the night is the prerequisite for an undisturbed and restful sleep. The most prevalent nocturnal breathing disturbance with morbid consequences is the obstructive sleep apnea syndrome. Forms severe enough to need therapy and, therefore, a thorough work-up, can be usually detected by a detailed history. Pathophysiology, clinical findings, differential diagnosis as well as work-up and therapy of the sleep apnea syndrome are discussed.

Airway Obstruction↗

[Long-term results of open parietal pleurectomy in treatment of recurrent spontaneous pneumothorax].

The open parietal pleurectomy is an effective treatment of recurrent or persistent spontaneous pneumothorax with a low recurrency rate of 3.3% in our series. The long-term course reveals very good functional results. A relatively high number of patients complains about chest wall pain or a painful thoracotomy scar. Also remarkable is the rate of dissatisfaction with the cosmetic result of the thoracotomy. Regarding both complaints thoracoscopic pleurectomy should be able to improve the results and the acceptance of this operation.

Adult↗