Ruptures trachéales au cours des traumatismes fermés cervico-thoraciques

Two cases are reported of tracheal fracture occurring during blunt cervico-thoracic trauma. The first case emphasized the impossibility of passing a tracheal tube below the fracture preoperatively, without the fibreoptic or rigid tracheoscope which has the added advantage of making an accurate diagnosis of the fracture. The clinical and paraclinical signs could only lead to a suspicion of the diagnosis, but not its confirmation. The second case showed the use of different ventilatory means during and after surgery (separate lung ventilation, jet ventilation, high frequency ventilation) in case of proximal fractures. The monitoring of intratracheal pressure should be used so as to have the best ventilation for the lowest pressures in the suture zone.     

Potential usefulness of quinine to circumvent the anthracycline resistance in clinical practice

Quinine, the widely used antimalaria agent, was found to increase the cytotoxicity of epideoxorubicin (epiDXR) in resistant DHD/K12 rat colon cancer cells in vitro. Quinine appeared as slightly less effective than quinidine or verapamil for anthracycline potentiation but its weaker cardiotoxicity could counterbalance this disadvantage in vivo. Serum from six patients treated by conventional doses of quinine (25-30 mg kg-1 day-1) was demonstrated to enhance the accumulation of epiDXR in DHD/K12 cells as judged by fluorescence microscopy and HPLC assay (1.6 to 6-fold compared with control serum). In this patients quinine concentrations in serum ranged from 4.4 to 10.1 micrograms ml-1. Our results suggest that quinine could be safely used as anthracycline resistance modifier in clinical practice.     

Dobutamine stress echocardiography identifies anthracycline cardiotoxicity.

BACKGROUND: Anthracyclines are effective anti-cancer agents, but their therapeutic value is limited by their myocardial toxicity. We assessed the physiological responses of stress echocardiography at low doses of dobutamine (DSE) in patients treated with anthracycline. METHODS AND RESULTS: In a prospective study, 28 patients were studied before and 1 month after the end of chemotherapy. All patients had normal ejection fraction (EF) at rest before therapy and the mean dose of anthracycline was 212+/-15 mg/m(2). Echocardiographic Doppler studies were performed before and during dobutamine infusion (5 and 10 microg/kg per min). Rest echocardiography demonstrated a significant decrease of EF between the two examinations in ejection fraction (67+/-3% vs. 61+/-3%, P<0.001). The increase of the EF during dobutamine infusion was higher after chemotherapy compared to the initial examination (19+/-3% vs. 29+/-3%: P<.05). No difference in EF was observed at 10 microg/kg per min between before and after chemotherapy. In contrast, at rest no difference in diastolic parameters was observed between the two examinations. Moreover, a significant decrease of the peak E and the ratio E/A was observed during dobutamine infusion after chemotherapy (93+/-4 cm/s vs. 79+/-5 cm/s and 1.3+/-0.1 vs. 1.0+/-0.1, respectively;P<0.05). CONCLUSION: Stress echocardiography may prove to be a sensitive technique and useful non-invasive approach for evaluating subclinical anthracycline cardiotoxicity.     

Phase II study of 3-hour infusion of high dose paclitaxel in refractory and relapsed aggressive non-Hodgkin's lymphomas. Groupe d'Etude des Lymphomes de l'Adulte

BACKGROUND AND OBJECTIVE: The first clinical studies of paclitaxel as a single agent for the treatment of relapsed or refractory low or intermediate grade non-Hodgkin's lymphomas (NHL) yielded controversial results regarding the response rates observed, mainly related to the dose and schedule of administration used. To obtain additional data concerning the efficacy and toxicity of paclitaxel in intermediate and high grade NHL we initiated a phase II study using a 3-hour infusion of high doses of paclitaxel. DESIGN AND METHODS: The eligibility criteria included patients with relapsed or refractory aggressive NHL, a performance status < or = 2 (WHO index), a platelet count > or = 100,000/microL, a neutrophil count > or = 2,000/microL, measurable disease, and adequate hepatic function. Patients were excluded if they were infected with HIV, had a left ventricular ejection fraction < 50%, or prior peripheral neuropathy. Paclitaxel was administered as a 3-hour infusion at a dose of 250 mg/m2 every 3 weeks for a maximum of 6 courses. RESULTS: Of 45 eligible patients, 42 received a total 73 courses of paclitaxel. Forty patients were assessable for response (89%), and 42 for toxicity (93%). Six patients (15%) achieved a partial (n = 4) or a complete remission (n = 2). Responses were observed in intermediate grade (n = 4) as well as in high grade lymphoma (n = 2). The main factor influencing the response to paclitaxel was the median duration of response to previous chemotherapy regimens which was 3 times longer in patients who responded to paclitaxel (16.3 months) than in patients who did not respond to paclitaxel (5.2 months) (p<0.05). The most common serious side effects were related to the hematologic toxicity of paclitaxel, and included grade IV granulocytopenia in 20 cases (48%), grade III/IV thrombocytopenia in 14 cases (33%) and grade III-IV anemia in 13 cases (31%). INTERPRETATION AND CONCLUSIONS: Despite frequent manageable hematologic toxicity, paclitaxel is usually well tolerated at a dose of 250 mg/m2 given by a 3-hour infusion. However, the clinical efficiency as a single therapy seems modest in relapsed or refractory aggressive lymphoma.     

Quinine improves the results of intensive chemotherapy in myelodysplastic syndromes expressing P glycoprotein: results of a randomized study

Intensive chemotherapy produces a lower complete remission (CR) rate in the myelodysplastic syndromes (MDS) than in de novo acute myeloid leukaemia (AML), possibly due in part to a higher incidence of P glycoprotein (PGP) expression in MDS blast cells. We designed a randomized trial of intensive chemotherapy with or without quinine, an agent capable of reverting the multidrug resistance (mdr) phenotype, in patients aged  65 years with high-risk MDS. Patients were randomized to receive mitoxantrone 12 mg/m²/d days 2–5 + AraC 1 g/m²/12 h days 1–5, with (Q⁺) or without (Q⁻) quinine (30 mg/kg/d). 131 patients were included. PGP expression analysis was successful in 91 patients. In the 42 PGP-positive cases, 13/25 (52%) patients in the Q⁺ group achieved CR, compared to 3/17 (18%) patients in the Q⁻ group ( P  = 0.02) and median Kaplan-Meier survival was 13 months in the Q⁺ group, and 8 months in the Q⁻ group ( P  = 0.01). No life-threatening toxicity was observed with quinine. In conclusion, the results of this randomized study show that quinine increases the CR rate and survival in PGP-positive MDS cases treated with intensive chemotherapy.     

High concentrations of intrathecal interleukin-6 in human bacterial and nonbacterial meningitis.

Interleukin-6 (IL-6) is multipotent cytokine that acts in a network of factors directing the inflammatory reaction of purulent bacterial meningitis (PBM). However, little is known about the role of IL-6 in aseptic or "viral" meningitis (AM). IL-6 was assayed by RIA in cerebrospinal fluid (CSF) and serum samples obtained from patients with AM (n = 65), PBM (n = 8), and lymphocytic bacterial meningitis (LBM, n = 11). Of patients with AM, 89% had detectable IL-6 in CSF, with high IL-6 titers (median, 2160 pg/mL; 95% confidence interval [CI], 1320-2540 pg/mL) compared with 100% in patients with PBM (median, 6575 pg/mL; 95% CI, 450-32,000 pg/mL) and 90.9% in patients with LBM (median, 875 pg/mL; 95% CI, 150-2180 pg/mL). There was a highly symmetrical correlation between IL-6 and the percentage of polymorphonuclear cells in CSF of patients with PBM (r = .97, P = .01) and AM (r = .49, P = .002). In conclusion, this study shows evidence that IL-6 is released into the meningeal space in aseptic meningitis and is correlated with the local acute inflammatory response.