Pentamidine and pancreatitis.
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Biomedical subjects
Publications and source records attributed to P Duroux.
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A statistical study compared a group of 38 patients with clinically and bacteriologically confirmed bacterial pneumonia with a control group of 33 subjects. Results facted to demonstrate any significant role for buccodental infection in the genesis of bronchopulmonary infections capable of inciting stomatologists to adopt drastic measures with respect to mortified teeth within the framework of pulmonary disease.
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Long-term treatment must be considered in cases of chronic asthma. Its main purpose is to suppress or decrease the frequency of acute dyspneic episodes; however, it may be more difficult to improve the bronchial obstruction of the patients. In allergic broncho-pulmonary aspergillosis, the treatment aims to prevent irreversible bronchiectasis. The methods and surveillance of long-term treatment are discussed.
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Sixty three patients with limited small cell lung carcinoma were entered into a pilot study alternating monthly cycles of combination chemotherapy (doxorubicin, VP16213, cyclophosphamide and methotrexate (group A) or cis platinum (group B) with 3 courses of mediastinal radiotherapy. The total mediastinal dose was 45 Gy for the first 28 patients (group A) and 55 Gy for the remaining 35 (group B). The complete response rate was 86% in group A (median survival 14 months) and 91% in group B (median survival 20 months). Local control at two years was 61% in group A and 82% in group B, while relapse-free 2 year survival rates were 32% and 37% respectively. The acceptable toxicity and high response rate of this combined modality therapy lead us to further research in maintenance therapy.
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Sixty-three evaluable patients with limited small cell lung carcinoma were entered into two pilot studies alternating 6 cycles of combination chemotherapy (Doxorubicin 40 mg/m2 d 1; VP16213 75 mg/m2 d 1, 2, 3; Cyclophosphamide 300 mg/m2 d 3, 4, 5, 6; and Methotrexate 400 mg/m2 d 2--plus folinic acid rescue--or Cis-Platinum 100 mg/m2 d 2) with 3 courses of mediastinal radiotherapy as induction treatment. The first course of radiotherapy started 10 days after the second cycle of chemotherapy; there was a 7 day rest between chemotherapy and radiotherapy courses. This 6 month induction treatment was followed by a maintenance chemotherapy. The total mediastinal radiation dose was increased from 4500 rad in the first study to 5500 rad in the second. Both protocols obtained a complete response (CR) rate of greater than 85% (with fiberoptic bronchoscopy and histological verification). Local control at 2 years was 61% in the first study and 82% in the second. Relapse-free survival at 2 years was 32 and 37%, respectively. Toxicity was acceptable. We conclude that our results justify further clinical research in alternating radiotherapy and chemotherapy schedules.
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An external spirometric method using a differential linear transformer was used to measure tidal volume (VT) and to determine factors influencing CO2 elimination and HFJV-induced "PEEP effect" in 15 critically ill patients under HFJV. VT increased with increasing driving pressure (DP) and decreasing frequency (f) and was influenced little by changes in I/E ratio. CO2 elimination, as reflected by the measurement of PaCO2, was mainly influenced by the absolute level of VT rather than by the product VT X frequency (PaCO2 = 5715/VT, r = 0.75, P less than 0.05). The primary phenomenon explaining HFJV-induced "PEEP effect" was intrapulmonary gas trapping due to incomplete exhalation of the first VT administered: the spontaneous relaxation times of these first VT were longer than expiratory time allotted to the ventilatory settings. HFJV-induced "PEEP effect" increased with I/E ratio, DP, and f and was markedly influenced by the mechanical properties of the total respiratory system. At given ventilatory settings, HFJV-induced "PEEP effect" was greater in patients with a normal or elevated time constant of the total respiratory system (tau RS) than in patients with a low tau RS. These results suggest that HFJV should not be used in patients with chronic obstructive pulmonary disease and asthma, and should be preferentially administered to patients having stiff lungs or decreased chest wall compliance.
Total parenteral nutrition (TPN) increases CO2 production (VCO2) in patients on intermittent positive-pressure ventilation who cannot match their CO2 excretion to the CO2 load, leading to an increase in PaCO2. We studied gas exchange and blood gas values in six patients with chronic respiratory failure, who were ventilated at low (6 +/- .7 L/min) and high (10 +/- 2 L/min) minute ventilation during three randomized nutritional regimens: control (255 kcal/day), glucose TPN (2550 kcal/day), and lipid TPN (3000 kcal/day). At the two levels of ventilation, TPN compared to control increased VCO2 and PaCO2 (p less than .01) and decreased pH (p less than .001). At low minute ventilation, the increase in VCO2 and the hypercapnic acidosis were less with lipid than with glucose TPN (p less than .05 and p less than .01, respectively). These results indicate that the risk of TPN-induced CO2 retention is lower if minute ventilation is increased before beginning TPN. Conversely, in patients with compromised ventilatory function, this risk could be higher during intermittent mandatory ventilation or weaning from the ventilator.
Thirty three evaluable patients with locally advanced squamous cell carcinoma of the lung were entered in a Phase II study combining chemotherapy (Vindesine 1.5 mg/m2 dl; CCNU 50 mg/m2 d2, 25 mg/m2 d3; Cis-Platinum 100 mg/m2 d3; Cyclophosphamide 200 mg/m2 d3, 4, 5) (VCPC) and radical radiotherapy to the primary tumor, mediastinum and supraclavicular nodes. Responders to chemotherapy resumed four additional cycles following radiation therapy. Fourteen patients (42%) presented an objective response to the first two cycles of VCPC. On final evaluation, 18 patients (54.5%) obtained a complete remission and 6 patients (18%) a partial remission. Median survival of all patients was 15.9 months and toxicity was acceptable. We conclude that our results justify a phase III study comparing combined treatment versus radiotherapy alone.
Thirty-three evaluable patients with locally advanced squamous cell carcinoma of the lung were entered in a phase II study combining chemotherapy (vindesine, lomustine, cisplatin, and cyclophosphamide) and radical radiotherapy. Fourteen patients had an objective response rate of 42% (two complete responses and 12 partial responses) with the first two cycles of chemotherapy. All patients received radiation therapy to the primary tumor, mediastinum, and supraclavicular nodes, and responders to chemotherapy received four additional cycles. On final evaluation, 18 patients (54.5%) achieved complete response and six patients (18%) achieved partial response. The objective response rate was 73% with the combined therapy. The median survival was 15.9 months. Toxicity was acceptable. We conclude that our results justify a phase III study comparing combined treatment versus radiotherapy alone.
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The physiopathology of chronic bronchitis consists of sequential reactions which progressively result in respiratory failure, blood gas abnormalities and finally, post-hypoxia cor pulmonale. Airway obstruction produces maldistribution of inspired gas and starts off a series of compensatory mechanisms with increased resting lung volume and prolonged expiration time resulting in diminution of tidal volume. Abnormal ventilation/perfusion ratios result in shunt and dead space effects, determine blood gas disorders and hypoxia due to reflex vasoconstriction and ultimately lead to pulmonary arterial hypertension with elevated cardiac output and increased vascular resistances. These physiopathological chain-mechanisms account for the clinical symptoms observed, including dyspnoea, episodes of acute bronchitis and in the end, signs of chronic cor pulmonale. They also indicate that the primary objective of treatment is to correct hypoxaemia. This can be achieved by continuous low flow rate oxygen therapy, by drugs capable of redistributing more evenly the ventilation/perfusion ratios and, accessorily, by respiratory analeptic agents. As regards the treatment of pulmonary arterial hypertension, one must admit that many uncertainties are still surrounding the use of vasodilators.
Bronchodilating drugs can be divided into three main groups: beta-adrenergic stimulants including specific beta-2 receptor agonists (salbutamol, terbutaline, fenoterol) which are the agents of this group used in everyday practice, theophylline and its derivatives, and atropine-like drugs (ipratropium bromide). Bronchodilators act chiefly upon the spasm observed at the bronchial level in reversible obstructive phenomena (mainly asthma), their effect upon inflammation and hypersecretion being slight or controversial. Beta-stimulants have a relatively specific mode of action at the bronchial level in the setting of use in pneumology; they exhibit cardiac effects only at high doses and when used by oral or parenteral routes. Relative to isoprenaline, they also have the advantage of being active orally and over a longer period of time. They are given in maintenance treatment of asthma, by parenteral or oral routes or as aerosols. Main side effects of adrenergic beta-stimulants are tremor with oral administration, and tachycardia with very high doses by parenteral or oral routes; when given as aerosols these agents may fail to control severe attacks. The bronchodilating properties of theophylline have been known for a long time; late advances concerning this drug result from better knowledge of its pharmacokinetics. Recent studies have discriminated between serum levels correlated with therapeutic effectiveness and those accompanied with mild or severe side effects; in addition, it has been clearly shown that the half life of this alkaloid varies from one person to another and with various physiopathologic (age, dietary habits, liver failure, heart failure...) or pharmacologic (drug interactions with enzyme inductors or inhibitors...) factors; these recent advances have led to improved individual adjustment of theophylline dosage using serum concentration assays if needed. Theophylline is used in acute attacks and in maintenance therapy of asthma. Main side effects are digestive intolerance and, with toxic doses, neurologic disorders. Atropine-like drugs inhibit the effects of the parasympathetic reflex which results from stimulation of receptors by irritation of the respiratory tract, through the action of mediators. In this group, ipratropium is the only drug given in aerosols; this, together with its pharmacologic specificity, contributes to its tolerance. In some instances, the bronchodilating effect of ipratropium bromide is comparable to that of sympathomimetics.
Many therapeutic aspects of venous thromboembolism continue to generate controversy so that the general therapeutic guidelines given below are only indicative. The first step is the diagnosis of venous thromboembolism; this is done in the vast majority of patients by visualization of blood clots using either pulmonary angiography or phlebography. The second step is to arrest the thrombotic process; the best means of doing this is to administer IV heparin. In the case of contra-indication or documented inefficacy of heparin therapy, the only therapeutic solution is to interrupt the inferior vena cava either with a clip, an umbrella or a filter. The blood clot lysis, which represents the third step, is effected by the natural fibrinolytic system. Thrombolytics , administered as a bolus of urokinase (15000 CTA U/kg), are indicated in cases of life-threatening pulmonary emboli, i.e. those with a pulmonary vascular obstruction of more than 50% and with hypotension, shock, or acute right ventricular failure. The use of thrombolytics is more questionable when they are administered to improve the quality of vascular patency. The only indication for pulmonary embolectomy is a contra-indication or inefficacy of thrombolytics . Due to the diagnostic and therapeutic difficulties, the first and most important part of the treatment of pulmonary emboli must be the broad application of prophylaxis treatment in patients with a high risk of venous thromboembolism.