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D Thevenin

Publications and source records attributed to D Thevenin.

At least 19 recordsLinked to original sources

Community-acquired pneumonia in the intensive care unit: epidemiological and prognosis data in older people.

OBJECTIVES: To compare epidemiological data, etiology, and prognosis of severe community-acquired pneumonia (CAP) in the intensive care unit (ICU) according to age (< or > or = 65 years) and to determine prognostic factors of CAP in older people. DESIGN: A retrospective (1987-1992) and prospective (1993-95) multicenter study. SETTING: Six ICUs in the north of France. PATIENTS: Five hundred five patients admitted to an ICU for severe CAP. MEASUREMENTS: Patient characteristics were compared with regard to age. Prognosis of CAP in older patients was studied by stepwise discriminant analysis. RESULTS: Two hundred seventy-eight patients (55%) were aged 65 years or older. Comparison of epidemiological data between older and younger patients revealed a higher prevalence of women (38% vs 29%), more severe underlying comorbidities (anticipated death within 5 years: 59% vs 26%), and more frequent chronic respiratory insufficiency (48% vs 33%) in the older patients. In this study group, 224 organisms were isolated from 172 patients (62%); those identified most frequently were Gram-negative bacilli (34%), S. pneumoniae (32%), and Staphylococcus sp. (19%). Compared with younger patients, no significant differences in bacteriological data were observed. However, crude and attributable mortality rates were significantly higher in the older patients (33% vs 21% and 30% vs 19%, respectively). Prognosis analysis identified four independent predictors of mortality in the older patients: initial septic shock (relative risk (RR) = 3), sepsis-related complications (RR = 4.3), hospital-acquired lower respiratory tract superinfections (RR = 2), and nonspecific pneumonia-related complications (RR = 2.8). CONCLUSION: The bacterial etiology provides some approaches to empirical therapy for older patients with severe community-acquired pneumonia. In addition, the inappropriateness of withholding intensive care for reasons of age alone is emphasized.

Age Factors↗

Can prolonged expiration manoeuvres improve the prediction of arterial PCO2 from end-tidal PCO2?

We have studied, in 16 patients undergoing thoracoabdominal oesophagectomy, if two prolonged expiration manoeuvres improve prediction of arterial PCO2 (PaCO2) from end-tidal PCO2 (PE' CO2). PE' CO2, PCO2 at the end of a simple prolonged expiration (PE1 CO2), and PCO2 at the end of a prolonged expiration preceded by sustained hyperinflation of the lungs (PE2 CO2), were measured during laparotomy, in the lateral thoracotomy position during two-lung ventilation, and after transition to one-lung ventilation. (PaCO2-PE' CO2) was 1.3 (SD 0.4) kPa during laparotomy and this remained stable throughout the study. Both manoeuvres decreased the mean arterial to peak expired PCO2 difference, particularly during one-lung ventilation. However, PE1 CO2 and PE2 CO2 did not agree more closely with PaCO2 than PE' CO2 at any stage of the study. We conclude that these manoeuvres did not improve estimation of PaCO2 from PE' CO2.

Aged↗

Community-acquired aspiration pneumonia in intensive care units. Epidemiological and prognosis data.

Over a 9-yr period, among 505 patients exhibiting severe community-acquired pneumonia and admitted into a total of six medical ICUs in the north of France, we collected 116 patients (23%) meeting the usual criteria for aspiration pneumonia. Main medical grounds of ICU admission were respiratory distress in 54 patients and neurological disturbances in 62 patients. The main underlying risk factor for aspiration pneumonia was drug overdose (39%). Mechanical ventilation was required for 73 patients. Initial shock was present in 15 patients. Pulmonary involvement was bilateral in 27 patients. There were 94 aerobic organisms isolated from 70 patients (60%), the most frequent being gram-negative bacilli (n = 38), Staphyloccus spp. (n = 27) and Streptococcus pneumoniae (n = 22). Overall mortality was 22%, but only 11 (11%) deaths were directly or indirectly related to aspiration pneumonia. Stepwise multivariate analysis identified four independent predictors of mortality: ineffective initial antimicrobial therapy (p = 0.0001), positive initial blood culture (p = 0.0001), hospital-acquired lower respiratory tract superinfections (p = 0.0054), and use of inotropic support (p = 0.0078). The importance of prevention of hospital-acquired superinfections and permanent optimization of our antimicrobial strategies warranting efficacy of the initial antimicrobial therapy is underlined.

Adult↗

Severe community-acquired pneumonia in ICUs: prospective validation of a prognostic score.

OBJECTIVE: To determine predictors of intensive care unit (ICU) mortality in patients with community-acquired pneumonia (CAP), to develop a pneumonia-specific prognostic index, and to evaluate this index prospectively. DESIGN: Combined retrospective and prospective clinical study over two periods: January 1987-December 1992 and January 1993-December 1994. SETTING: Four medical ICUs in the north of France. PATIENTS: Derivation cohort: 335 patients admitted to one ICU were retrospectively studied to determine prognosis factors and to develop a pneumonia-specific prognostic index. Validation cohort: 125 consecutive patients, admitted to four ICUs, were prospectively enrolled to evaluate this index. RESULTS: In the derivation cohort, 16 predictors of mortality were identified and assigned a value directly proportional to their magnitude in the mortality model: aspiration pneumonia (-0.37), grading of sepsis > or = 11 (-0.2), antimicrobial combination (-0.01), Glasgow score > 12+mechanical ventilation (MV) (+0.09), serum creatinine > or = 15 mg/l (+0.22), chest involvement shown by X-ray > or = 3 lobes (+0.28), shock (+0.29), bacteremia (+0.29), initial MV (+0.29), underlying ultimately or rapidly fatal illness (+0.31), Simplified Acute Physiology Score > or = 12 (+0.49), neutrophil count < or = 3500/ mm3 (+0.52), acute organ system failure score > or = 2 (+0.64), delayed MV (+0.67), immunosuppression (+1.38), and ineffective initial antimicrobial therapy (+1.5). An index was obtained by adding each patient's points. According to a receiver operating characteristic curve, the cut-off value of this index was 2.5. In the validation cohort, an index of > or = 2.5 could predict death with a positive predictive value of 0.92, sensitivity 0.61, and specificity 0.98. CONCLUSION: This index, which performs well in classifying patients at high-risk of death, may help physicians in initial patient care (appropriateness of the initial antimicrobial therapy) and guide future clinical research (analysis and design of therapeutic trials).

Adolescent↗

Treatment of relapsing and refractory adult acute myeloid leukemia according to in vitro clonogenic leukemic cell drug sensitivity.

In an attempt to improve the results of treatment in patients with relapsing or refractory acute myeloid leukemia (AML), we conducted a pilot study using a two-drug salvage regimen according to the in vitro clonogenic leukemic cell (CFU-L) drug sensitivity. Fourteen patients were included in the study, 10 with relapsing and 4 with refractory AML. Drug exposure was assessed for daunorubicin, cytosine arabinoside, etoposide, mitoxantrone and amsacrine. The two drugs with the best inhibitory effect on CFU-L were selected for the treatment. A complete remission was achieved in only 4 patients and a partial remission in 3 patients. Although the number of patients is too small for appropriate statistical analysis and for a definite conclusion to be drawn, the observed response rate with directed therapy did not appear better than that expected from empiric salvage regimen.

Adult↗

In vitro effect of P-glycoprotein (P-gp) modulators on drug sensitivity of leukemic progenitors (CFU-L) in acute myelogenous leukemia (AML).

Cyclosporine A (CyA), a potent reversant of multidrug resistance (mdr), was studied for its effects on the sensitivity of leukemic progenitors (leukemia colony-forming units, CFU-L) to daunorubicin (DNR) and mitoxantrone. CyA was first compared to verapamil and cefoperazone for reversion of mdr in the mdr1+ cell line K562/DOX. A dramatic increase of sensitivity to 10(-6) M DNR was noted with CyA (0.5 and 1 microgram/ml) and verapamil (1 and 5 micrograms/ml), but not for cefoperazone (0.3 and 0.6 mg/ml). The sensitivity of K562/DOX to 10(-6) M mitoxantrone was also slightly enhanced by CyA. The change in CFU-L drug sensitivity in the presence of CyA was then tested in 12 relapsing/resisting patients and in 3 untreated patients with acute myelogenous leukemia (AML). No change in CFU-L sensitivity to DNR was noted, despite the presence of a subset of P-glycoprotein positive (P-gp+) cells in three out of the ten evaluable cases. Among the six evaluable cases tested with mitoxantrone and CyA, an increase of 50% in CFU-L sensitivity to mitoxantrone was noted in one (of three) P-gp+ patient. These data suggest that the CFU-L in AML rarely expressed the P-gp and that other mechanisms of drug resistance could be involved in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Cancer of the upper cervico-thoracic esophagus].

Between 1984 and 1990, 90 operations were performed for carcinoma of cervical and cervicothoracic esophagus. All tumors were squamous cell carcinoma. Of these patients, 78 underwent esophagectomy, and 12 had had a gastric by pass. Visceral remplacements employed the whole stomach. Only one cervicothoraco-laparotomy was performed. The operative mortality was 6.6% (no difference between mortality rate associated with pharyngogastric anastomosis (5.3%) and that with cervical esogastric anastomosis (7.1%). The 78 resections included 55 esophagectomies for cure (70.5%) and palliative procedure for the 23 other patients. Post operative complication rate was 38% and 5-year survival rate was 12%. One study suggested that resectability and immediate post operative results of cervical or cervicothoracic esophagus cancer are not different from these of intrathoracic esophageal cancer. These results encouraged an aggressive surgical approach; whole gastric pull up seems to be the safest and most reliable method for cervical anastomosis as well as for pharyngeal anastomosis, difficulty of correct lymphadenectomy, low 5-year survival, advocated adjuvant radiotherapy and/or chemotherapy.

Adult↗

Multivariate analysis of prognostic factors in acute myeloid leukemia: value of clonogenic leukemic cell properties.

The initial clinical and biological parameters, including clonogenic leukemic cell (CFU-L) assay, were reviewed for their prognostic significance in a cohort of 188 adult patients with newly diagnosed untreated acute myeloid leukemia (AML). Almost all patients received induction therapy with daunorubicin (DNR) and cytarabine (Ara-C) according to the European Organization for Research and Treatment of Cancer (EORTC) AML 5 to AML 9 trials. Bone marrow samples from 116 representative patients were obtained for CFU-L assay with an efficiency percentage of 89.6%; 76 patients had a measurement of the CFU-L self-renewal capacity (second plating efficiency [PE2]) and 91 patients had CFU-L inhibition test after exposure to DNR and/or Ara-C. The prognostic significance of parameters such as age, hematological antecedent, WBC count, liver enlargement, and Auer rods is confirmed in the present study. Moreover, high platelet and polymorphonuclear counts appeared to be related to resistance to induction course. However, through multivariate analysis, CFU-L sensitivity to drugs and self-renewal capacity appeared to be major independent prognostic factors in AML. A low CFU-L inhibition in the presence of the DNR and Ara-C combination correlates with a poorer complete remission (CR) rate, but not with CR duration. Patients with the lower PE2 values experienced both higher CR rate and longer CR duration. The practical interest of CFU-L study remains to be defined but, at least, PE2 measurement could be considered in the future as a major variable in determining therapeutic aggressiveness.

Adolescent↗

Exclusive use of calcium channel blockers in preoperative and intraoperative control of pheochromocytomas: hemodynamics and free catecholamine assays in ten consecutive patients.

This study investigates the role of nicardipine hydrochloride in preoperative and intraoperative blood pressure control and intraoperative catecholamines (norepinephrine and epinephrine) release in 10 patients undergoing pheochromocytoma resection. Nicardipine was used orally in the preoperative period for either 1 or 8 days (60 to 120 mg/24 hr) and then was infused during anesthesia until tumor removal, continuously at a rate of 2.5 to 7.5 micrograms/kg/min, depending on systolic arterial pressure level. All patients were successfully operated on. No severe hypertensive crisis occurred during tumor manipulation, although several patients had a 3- to 85-fold (norepinephrine) and 3- to 40-fold (epinephrine) increase of catecholamines from baseline levels. Hemodynamics data suggest that nicardipine caused significant inhibition of vascular smooth muscle contraction (42% decrease in systemic vascular resistance); calcium-dependent catecholamines release was not inhibited by nicardipine infused as mentioned. Use of nicardipine may be recommended for perioperative and intraoperative control of pheochromocytomas and might substitute for routine alpha-adrenergic blockade.

Adrenal Gland Neoplasms↗

[Pheochromocytoma. Experience of 60 operations].

Between 1971 and 1987, 60 patients presenting 68 pheochromocytomas were operated on in the University Teaching Hospital of Lille. Diagnosis has been transformed by the use of CT scan, which for the last 10 years has enabled the lesion to be more reliably localized than by MIBG scintigraphic scanning. Combination of the two investigations enables the diagnosis to be confirmed in 100% of cases. The following topics are covered: preparation for surgery with the indications for alpha and beta blockers, route of approach--preferably median laparotomy--and operative sequelae as a function of the benign or malignant nature of the tumor.

Adrenal Gland Neoplasms↗

In vitro sensitivity of normal and leukemic myeloid clonogenic cells to hyperthermia: absence of selective effect.

The in vitro heat sensitivity of myeloid clonogenic cells was tested in 22 normal marrows (granulo-monocytic progenitors) and in 40 marrows of patients with acute myelogenous leukemia (leukemic progenitors). Cells were treated for 1 h at 42 degrees, 43 degrees, 44 degrees, or 45 degrees C prior to plating. A temperature-dependent inhibition of growth was seen without a selective effect on the two kinds of progenitors. Because these two kinds of progenitors have the same heat sensitivity, hyperthermia should not be used alone as a technique for in vitro depletion of residual myeloid leukemic cells.

Bone Marrow Cells↗

Comparison of in vitro inhibition of etoposide (VP16) on leukemic and normal myeloid, erythroid clonogenic cells.

We have compared in various clonogenic assays the in vitro sensitivity to etoposide (VP16) of 1) human leukemic precursors (leukemia colony-forming units; L-CFU), 2) normal erythroid progenitors (erythroid burst-forming units; BFU-E, and 3) normal committed myeloid progenitors (granulocyte-macrophage colony-forming units; CFU-GM and more primitive hemopoietic precursors (PPC) that adhere to cultured marrow stromal cells. Bone marrow samples were obtained from 15 normal subjects and 16 leukemic patients: 9 in the acute phase of acute nonlymphoblastic leukemia (ANLL) and 7 in complete remission. VP16 was tested at concentrations ranging from 10(-8) to 10(-3) M. The median recoveries at 10(-3) M VP16 were respectively 0%, 0.5%, 0%, and 0% for leukemic progenitors, CFU-GM from leukemic patients in complete remission, normal CFU-GM, and BFU-E, and 23% for PPC. This indicates that CFU-GM, BFU-E, and L-CFU are highly sensitive to VP16, whereas PPC, more primitive myeloid precursors, are spared. These results suggest that VP16 may be used as an "ex vivo" purging agent for autologous bone marrow.

Cell Survival↗

In vitro sensitivity of clonogenic cells in resisting and relapsing patients with acute myelogenous leukaemia.

The evolution of in vitro bone marrow clonogenic leukaemic cells (CFU-L) drug sensitivity was studied in 23 patients with acute myeloid leukaemia treated with anthracycline and cytosine arbinoside (ara-C). In 12 patients tested before and after first induction treatment failure (interval: 6 +/- 4 weeks), the sensitivity remained stable for daunorubicin and showed little variation for ara-C. Among eleven patients tested before treatment and at first relapse (interval: 13 +/- 7 months), in vitro CFU-L sensitivity revealed no correlation between the two measurements, and a trend in decreased sensitivity to daunorubicin and ara-C. These findings suggest that induction failures could be related to factors other than simple selection of a resistant CFU-L subclone.

Adult↗

Detection of residual disease in acute myeloid leukemia using light density gradients and culture assay.

For monitoring the effect of chemotherapy in acute myeloid leukemia (AML), we attempt to detect minimal numbers of AML clonogenic cells (CFU-L) during remission using light density gradients combined with PHA-LCM methyl cellulose assay. Fifteen patients in complete remission (CR) of AML were studied: 8 patients with Auer Rods (AR+), and 7 without Auer Rods (AR-). The cluster/colonies ratio and the granulocytic maturation of cells from pooled colonies were not significantly different whatever the density cut used (1077, 1062 or 1059). In all the AR+ patients, few AR+ cells (.06% +/- .03) were observed in bone marrow cultures during remission, without differences between density gradients, but not before plating. These AR+ cells were not found in culture of AR- patient bone marrows nor in normal marrows. The serial studies performed in 6 patients (4 AR+, 2 AR-) were not contributive for relapse prediction. In 2 cases, the second examination failed to detect AR+ cells: one was performed after an autologous bone marrow transplantation and the other in a patient with prolonged CR (54+ months). A quantitative analysis of residual CFU-L with our technique requires a cytological examination of each colony, that is very time consuming and limits its routine use.

Adult↗

In vitro depletion of clonogenic cells in adult acute lymphoblastic leukemia with a CD10 (anti-cALLA) monoclonal antibody.

A semi-solid medium colony assay was used in common acute lymphoblastic leukemia (cALL) to test growth inhibition of leukemic progenitors (CFU-L) after exposure to monoclonal antibodies (MoAbs) directed against CD10 and CD9 antigens. Peripheral or bone marrow cells from 15 patients were plated after exposure to various concentrations of ALB2, a CD10 cytotoxic MoAb, followed by complement lysis. CFU-L inhibition was complete (no residual colony) in 5 cases (33%), marked (greater than or equal to 95%) in 4 cases (27%), but only moderate (64% +/- 28) in 6 cases (40%). This inhibition was not related to the percentage of cALLA positive cells before exposure to MoAb. In addition, cells of 5 patients were exposed to BA1 (CD24) + complement. In these cases, the proportion of CFU-L inhibition was equal to or higher than with ALB2. In 3 cases, cells were exposed to an association of ALB2 and SB4 (CD19) MoAbs followed by complement lysis, with a marked inhibition (greater than or equal to 99%) in 2/3 cases. These observations give supplementary support to the use of several MoAbs directed against various antigens present at early stages of B differentiation.

Adolescent↗

Prognostic value of in vitro uptake and retention of cytosine arabinoside in acute myelogenous leukemia.

In vitro uptake and retention of 3H-cytosine arabinoside (ara-C) was studied in 68 acute myelogenous leukemia (AML) patients (ten were studied twice) treated with a regimen containing conventional (54 patients) or high doses (24) of ara-C. Drug uptake and retention after four hours were measured following 30 minutes exposure to 1 and 50 micrograms/mL of ara-C. A good correlation was observed between high uptake in the acid soluble (AS) fraction (P less than .01), or high retention in the acid insoluble (Al) fraction (P less than .03) of 1 microgram, but not 50 micrograms, of the drug and obtainment of complete remission (CR) in patients treated with conventional doses of ara-C. Patients with a high percentage of ara-C retained in the AS fraction (greater than 26%) have a significantly longer CR duration than patients with a lower level of retention (P less than .02). In 17 patients who achieved a CR in spite of a low tritiated ara-C uptake, the clonogenic leukemic (CFU-L) cells were especially sensitive to drugs (15 of 17 v three of 11 among resisting patients).

Amsacrine↗