[Necrotic leg ulcers after topical application of chlormethine]. / Ulcères de jambe nécrotiques après application locale de chlorméthine.

BACKGROUND: Topical chlormethine has been widely used in the early stages of mycosis fungoides for many years. Cutaneous reactions (skin irritation and itch) are the most frequent adverse effects. Herein we report a rare side effect: severe necrotic leg ulcers. PATIENTS AND METHODS: An 82-year-old woman with a history of high blood pressure developed hyperalgesic necrotic ulcers on the lower limbs following local trauma one month after initiation of topical chlormethine (Valchlor®) to treat mycosis fungoides. Aetiological examination showed moderate peripheral arterial disease which, while constituting an aggravating factor, did not account fully for these skin ulcers. Moreover, drug-induced ulcer was suspected on account of the chronology. Dermal corticoids and topical treatment were prescribed in place of chlormethine and led to a favourable outcome. CONCLUSION: Incrimination of chlormethine was based on the chronological and semiological criteria. This is the first published case of leg ulceration induced by Valchlor®.

Genetic context of plasmid-carried blaCMY-2-like genes in Enterobacteriaceae.

Analysis of 15 European clinical Enterobacteriaceae isolates showed that differences in the genetic context of blaCMY-2-like genes reflected the replicon type, usually IncA/C or IncI1. These blaCMY-2 loci may originate from the same ISEcp1-mediated mobilization from the Citrobacter freundii chromosome as structures described in earlier studies.

[When to ask for a skin biopsy in a patient with leg ulcer? Retrospective study of 143 consecutive biopsies]. / Quand poser l'indication d'une biopsie cutanée chez un patient porteur d'ulcère de jambe ? Étude rétrospective sur 143 biopsies consécutives.

OBJECTIVE: A vascular cause is found in around 85% of leg ulcer patients, but non-vascular causes are also observed. Their diagnosis is based on a set of clinical arguments and skin biopsy with histological analysis. The aim of this study was to analyze the results of these biopsies and to find common criteria for ulcers whose skin biopsies had led to the diagnosis of a non-vascular ulcer. MATERIAL AND METHOD: A retrospective study was carried out on the analysis of 143 skin biopsies of leg ulcers. The reasons for the biopsy were mainly atypical clinical signs and/or the lack of improvement in care after 6 months, as advocated by the French health authorities. RESULTS: The skin biopsies led to a diagnosis of non-vascular ulcer in 4.9% of cases (7/143), including skin cancer (n=5, 3.5%), cutaneous leishmaniasis (n=1, 0.7%) and Pyoderma gangrenosum (n=1, 0.7%). The univariate statistical analysis revealed that an elevated rim and abnormal excessive granulation tissue were significantly more frequently found in these ulcers. All patients with a positive skin biopsy had associated vascular involvement. CONCLUSION: This study found a 5% rate of non-vascular causes of ulcers, mainly skin cancer. Elevated rims and abnormal excessive granulation tissue were the unusual features most commonly found in these ulcers. All patients whose skin biopsy revealed a non-vascular cause had associated vascular involvement. This information confirms the need to perform a skin biopsy, even in the presence of a vascular disease.

Supervised short-stretch compression therapy in mixed leg ulcers.

OBJECTIVES: This study was conducted to determine hemodynamic and clinical tolerance under short-stretch compression therapy in elderly patients suffering from mixed-etiology leg ulcers. DESIGN: Transversal observational study conducted in 25 hospitalized patients with a moderate peripheral arterial occlusive disease defined as an ankle-brachial pressure index>0.5, an ankle pressure of>70mmHg and a toe cuff pressure (TP)>50mmHg. MATERIAL AND METHODS: Short-stretch bandages were applied daily with pressures from 20 to 30mmHg. Ankle-brachial pressure, great toe laser Doppler flowmetry (LDF) and transcutaneous oxygen pressure (TcPO2) on dorsum of the foot were measured at baseline and after its removal at 24hours. Great toe LDF was also measured at 10minutes after bandage application. Compression pressure (CP) was measured with a sub-bandage device at baseline, at 10minutes and before bandage removal at 24hours. Clinical tolerance was evaluated taking into account the patient's pain and skin tolerance. RESULTS: Mean age of patients was 80±15 years. Median duration of ulcers was 18 months. Hypertension was highly prevalent. One third of patients had diabetes. Toe pressure index and TcPO2 values did not significantly change under compression therapy (P=0.51 and P=0.09, respectively) whereas CP decreased significantly during 24hours. The loss of CP was significant 10minutes after bandage application (P<0.001). Nearly all ulcers were painful prior to placement of compression therapy and required level 1 analgesics. One patient required level 2 analgesic for pain relief. No increase in pain and no ischemic skin damage occurred under compression therapy. CONCLUSIONS: In elderly patients with mixed leg ulcers and with an absolute TP>50mmHg, short-stretch compression of up to 30mmHg does not adversely affect arterial flow and appears clinically well tolerated. Such bandages with appropriate levels of compression may aid ulcer healing by treating the venous part of the disease.

[Deep venous thrombosis of the upper limb in a violin player: The "bow syndrome"]. / Thrombose veineuse profonde du membre supérieur chez une violoniste : « le syndrome de l'archet ¼.

BACKGROUND: Exercise-induced thrombosis is a rare cause of deep venous thrombosis (DVT) of the upper limb and usually affects young subjects without comorbid conditions. The diagnosis may be challenging. CASE REPORT: A 23-year-old female right-handed French teacher and amateur violin player presented with edema of the root of the right arm associated with erythrocyanosis of the extremity and collateral circulation of the shoulder. History taking revealed oral contraception and recent change in violin playing habits. D-dimers were negative. A second duplex-Doppler was required before visualization of a DVT in the right subclavian vein. The patient was given low-molecular-weight heparin alone, followed by rivaroxaban. The outcome was very favorable at 48h. The patient was seen at 4 months and had not had a recurrent episode. DISCUSSION: The diagnosis of DVT of the upper limb is basically clinical. There is a clinical probability score for the introduction of anticoagulation even if the duplex-Doppler fails to visualize DVT, a situation that can occur due to the clavicular superposition in this region. Exercise-induced DVT should be suspected in patients with minimally intense but repeated exercise (hyper-abduction), e.g. as here playing the violin. Anticoagulation is the treatment of choice. The role for surgery and pharmacomechanical strategies remains to be defined. CONCLUSION: Exercise-induced thrombosis (Paget-Schroetter syndrome) should be suspected in young patients free of any comorbidity who develop a thrombosis of the upper limb. Studies comparing different therapeutic options would be useful to achieve more homogeneous management practices despite the heterogeneous clinical presentations.

Dose-intensity of a four-drug chemotherapy regimen with or without recombinant human granulocyte-macrophage colony-stimulating factor in extensive-stage small-cell lung cancer: a multicenter randomized phase III study.

PURPOSE AND METHODS: We investigated whether a high-dose chemotherapy regimen of cyclophosphamide 1,800 mg/m2, 4'-epidoxorubicin 60 mg/m2, etoposide 330 mg/m2, and cisplatin 120 mg/m2 given monthly for four cycles with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) support (5 micrograms/kg daily for 10 days) could improve the survival of patients with extensive-stage small-cell lung cancer (SCLC) compared with a standard-dose regimen (cyclophosphamide 1,200 mg/m2, 4'-epidoxorubicin 40 mg/m2, etoposide 225 mg/m2, and cisplatin 100 mg/m2) given monthly for six cycles. Planned cumulative doses of the drugs were the same in both treatment arms except for cisplatin (which was 80% in the higher-dose plus rhGM-CSF group). RESULTS: At the time of the preplanned interim analysis, 125 patients, 60 in the standard-dose group and 65 in the higher-dose plus rhGM-CSF group, had entered the study; 116 were eligible, 55 in the standard-dose group and 61 in the higher-dose group. All patients were included in the analyses. The cumulative doses of each drug actually delivered were significantly higher in the standard-dose group. No difference in response rates was observed between the two groups. There were significantly greater hematologic toxicities, documented infections, and transfusions of RBCs and platelets in the higher-dose plus rhGM-CSF group. Patients in this group proved to have a shorter survival duration and a shorter time to relapse than patients in the standard-dose group (median overall survival: standard-dose, 10.8 months; higher-dose, 8.9 months; log-rank test with adjustment for prognostic variables, P = .0005; respective probabilities of relapse at 1 year, 77 +/- 0.6 and 96 +/- 2.2; log-rank test, P = .013). CONCLUSION: A 50% increase in dose-intensity for this four-drug regimen could not be achieved with GM-CSF due to excessive toxicity in patients with extensive-stage SCLC.

First description of DHA-1 ampCbeta-lactamase in Proteus mirabilis.

This report describes the first occurrence of the DHA-1 ampCbeta-lactamase gene in Proteus mirabilis. The organism was isolated from the vaginal flora of a pregnant woman in a French hospital. The DHA-1 beta-lactamase gene was identified on the basis of phenotypic characteristics, PCR amplification and sequencing. Antagonism between cefoxitin and the other cephalosporins suggested inducible production of the DHA-1 enzyme.

[Spontaneous thrombosis of lesion-free carotid arteries: a retrospective analysis of eight patients]. / Thrombus endoluminal de l'artère carotide sans lésion sous-jacente. Etude rétrospective de 8 patients.

Strokes are rarely secondary to spontaneous carotid artery thrombosis. The objectives of this retrospective analysis were to define characteristic features and the clinical course. The study population included eight patients (6 females/2 males) seen at six university neurological centers. Age of onset was 46.5 years (range 38-52). Half of the patients had no vascular risk factor. Symptoms were TIA (n=1), strokes (n=7). Echotomography revealed intraluminal thrombus, with occlusion in 2 cases. Thrombi were found in common carotid artery (n=3), carotid bifurcation (n=2) and internal carotid artery (n=3). The thrombus was mobile in 4 cases. Seven patients were treated by anticoagulation therapy, one by surgery because of recurrent TIA. Further echotomographic exams revealed total resolution (3 cases) or decrease of the thrombus (3 cases). Occlusion was definitive in one patient. A cause was identified in six patients: acute leukemia (n=1), thrombocytopenic purpura (n=1), iron deficiency anemia (n=4).

[Peripheral artery occlusive disease of the lower limbs: Rapid aggravation in a patient taking nilotinib for chronic myeloid leukemia]. / Artériopathie des membres inférieurs d'aggravation rapide chez un patient traité par nilotinib pour leucémie myéloïde chronique.

The development of tyrosine kinase inhibitors (TKI) has revolutionized management of patients with chronic myeloid leukemia (CML), transforming this fatal disease into a chronic disease with nearly normal life expectancy. Nilotinib is a second generation TKI targeting the oncoprotein BCR-ABL used in patients in the chronic phase of CML. Several research teams have suggested over recent years that nilotinib might be the causal agent in the development or aggravation of vascular disease, particularly in patients with cardiovascular risk factors or an established cardiovascular disease. We report here the case of a patient who developed severe peripheral arterial disease of the lower limbs that worsened despite optimal medical and surgical care, presenting recurrent re-stenoses after different revascularization techniques (bypass, angioplasty…) associated with aggravation of severe trophic disorders to the point of potentially requiring amputation. Discontinuation of nilotinib enabled a stabilization of the arterial lesions and complete healing of the trophic lesions. This case illustrates the importance of recognizing co-morbid conditions in patients with severe vascular disease and to examine the possibility of drug interactions leading to rapid aggravation of arterial disease with no other cause. Studying the pathophysiological impact of TKIs on the vascular system may open new avenues of research for the investigation of factors triggering arteriosclerosis.

Impaired skeletal muscle endurance related to physical inactivity and altered lung function in COPD patients.

STUDY OBJECTIVE: The aims of this work were to determine (1) whether patients with COPD have impaired skeletal muscle performance (ie, maximal strength and endurance) compared with healthy subjects, and (2) whether the level of physical activity, body composition, and lung function are related to skeletal muscle performance in COPD patients. METHODS: Seventeen COPD patients and eight healthy age-matched control subjects performed maximum voluntary contraction (MVC) of the quadriceps and an endurance test consisting of dynamic contractions of the quadriceps against 20% of MVC at an imposed regular pace until exhaustion. The endurance test duration determined the muscle "limit time" (Tlim). A score of physical activity (PA score) was obtained using an adapted physical activity questionnaire for the elderly, and body composition was measured by the bioelectrical impedance method. Symptom-limited oxygen uptake (VO2 sl) was also assessed in COPD patients using a maximal incremental exercise test. RESULTS: The results showed that Tlim and PA score were significantly decreased in COPD patients (p<0.05). Significant positive correlations were found in the COPD group between Tlim and the PA score (r=0.60; p<0.05), FEV1 (r=0.52; p<0.05), and PaO2 (r=0.63; p<0.05). The same results were found between the PA score and VO2 sl (r=0.57; p<0.05) and FEV1 (r=0.63; p<0.05). CONCLUSION: These findings indicate impaired skeletal muscle endurance in COPD patients related to altered lung function and associated physical inactivity.

Chest tumor response during lung cancer chemotherapy. Computed tomography vs fiberoptic bronchoscopy.

Tumor response is one of the most important criteria in the analysis of chemotherapy. A chest computed tomographic (CT) scan and fiberoptic bronchoscopy (FOB) might give different results, as they analyze different aspects of the effects of chemotherapy on lung cancer. The response of the chest tumor in 103 patients with stage III or IV lung cancer (35 with small-cell lung cancer [SCLC] and 68 with non-small-cell lung cancer [NSCLC]) who prospectively entered chemotherapy trials was studied in order to determine the concordance between the chest CT scan and FOB. The chest CT scan allowed an assessment of tumor response in almost all patients, whereas FOB was not able to evaluate this response in 15 of the 103. The frequency of an evaluable endobronchial lesion did not depend on histology (SCLC, 97 percent; NSCLC, 93 percent; chi 2 = 0.85; not significant [NS]) or tumor T classification (T1-2, 83 percent; T3, 94 percent; T4, 97 percent; chi 2 = 1.49; NS). Tumor location in the bronchial airway did not differ when SCLC and NSCLC were compared. Thus, it is not possible to predict a subgroup of patients in whom FOB may be optional. In the group of 88 patients who were evaluable for response using both FOB and CT scan, a statistical concordance of the response classification was observed. The response was overevaluated by CT scan in 22 patients for whom data obtained by FOB appeared to be critical in the evaluation of tumor response. The concordance of response data obtained when the 2 methods were used was lower in NSCLC in comparison with SCLC. Thus, the use of FOB in the analysis of tumor response might be important, especially for NSCLC, inasmuch as FOB modulates the CT-evaluated response.

Interleukin-1 alpha and soluble interleukin-2 receptor during small cell lung cancer chemotherapy: comparison of high chemotherapy dose with rhGM-CSF and standard chemotherapy dose without rhGM-CSF.

This study was designed to analyze the possible immunomodulation induced in vivo by haematopoietic growth factors following anti-cancer chemotherapy. Haematologic and cytokine kinetics (IL-1, IL-6, TNF alpha and soluble interleukin-2 receptor (sIL-2R)) were studied in patients with SCLC receiving high dose regimens of chemotherapy and recombinant human GM-CSF (group A), or standard doses of chemotherapy without rhGM-CSF (group B). Six patients were prospectively enrolled and randomized in each group. The kinetics of haematopoiesis following chemotherapy did not significantly differ between the two groups. In group A, the plasma sIL-2R level increased regularly during rhGM-CSF treatment reaching a 2.5-fold elevation at day 12 whereas it remained stable in group B. Conversely, IL-1 alpha decreased to an undetectable level in group A whereas it increased slightly from day 14 to day 18 in group B. As sIL-2R could compete with lymphocyte surface receptors and as IL-I is an important cytokine involved in acute phase response, our results might be regarded as reflecting a transient decrease in the cell-mediated immune response in small cell lung cancer patients receiving high dose chemotherapy combined with rhGM-CSF.

r-metHuG-CSF support to ifosfamide, cisplatin, etoposide chemotherapy in non-small cell lung cancer.

Twenty patients with locally advanced or metastatic non-small cell lung cancer entered a study of recombinant human methionyl G-CSF (r-metHuG-CSF) as an adjunct to ifosfamide, cisplatin and etoposide (IPE) regimen. Chemotherapy consisted of three courses of cisplatin 25 mg/m2, ifosfamide 1.5 g/m2 (with uroprotection) and etoposide 100 mg/m2 given on days 1-4 of a 21-day cycle. r-metHuG-CSF, 5 micrograms/kg, was administered subcutaneously from day 5 to day 14. Eighteen out of 20 patients completed the three courses (57 evaluable cycles). Grade 3-4 neutropenia affected 50, 42 and 22% of the patients during cycles 1, 2 and 3, respectively, whereas thrombocytopenia was observed in 25% of the patients throughout the chemotherapy protocol. Haematological toxic events requiring transfusions and/or antibiotics were responsible for 11 unplanned hospitalizations. Among these only three were exclusively devoted to febrile neutropenia care, the remaining eight being mainly required for blood transfusions. There were no deaths during the study duration. Dose reductions were needed in 65% of the patients and chemotherapy was delayed by thrombocytopenia in five patients. The total relative dose intensity was 84%. Eleven (55%) patients responded (one complete and 10 partial responses). Median survival was 9.5 months. We concluded that IPE combination chemotherapy can be administered safely with the support of r-metHuG-CSF inasmuch as neutropenia appears as mild to moderate and manageable. Optimal delivery of chemotherapy is still limited by other toxicities, mainly thrombocytopenia, but the successful relative dose intensity observed herein deserves further studies designed to analyze a dose intensity-survival relationship in non-small cell lung cancer.

Immunohistochemical study of P-glycoprotein distribution in lung cancer.

Indirect immunoperoxidase was used to determine the reactivity of C219 (P-glycoCHEK C219, Centocor Diagnostics, Malvern, PA), a monoclonal antibody (Mab) with high affinity for an internal epitope of the P-glycoprotein encoded by the multidrug resistance (MDR1) gene, in 40 surgically resected primary lung tumours. C219 reactivity was qualitatively classified in seven small cell lung cancers (SCLC), 29 non small cell lung cancers (NSCLC), and four carcinoid tumours. Ploidy was analysed by means of static cytometry using a computer-assisted image processor following Feulgen staining of cytologic prints of 32/40 lung tumours. Indirect immunoperoxidase reactivities of Mabs S-L 11.14 and MOC-1 were also studied to characterize the expression of cluster 1 lung cancer antigens and hence to determine among the NSCLC those which expressed the neural cell adhesion molecule (NCAM). Eighteen (45%) lung tumours strongly expressed P-glycoprotein as an immunostaining of many islets of malignant cells or almost all malignant cells. In addition, 8/40 tumours (20%) showed a weak reactivity (few immunostained cells) and 14/40 (35%) no reactivity. There was no difference of reactivity when NSCLC were compared with SCLC. The expression of P-glycoprotein in NSCLC did not vary significantly when the stage of disease was considered. Among the 29 NSCLC, 10 (36%) expressed S-L 11.14 and MOC-1. The NCAM positive NSCLC did not show any difference of P-glycoprotein expression in comparison with NCAM negative ones. Finally, C219 immunoperoxidase reactivity did not significantly differ according to the ploidy status. In conclusion, the internal epitope of the P-glycoprotein encoded by the MDR1 gene is frequently expressed by lung tumours of any histological type. This expression is not higher in Stage III and IV lung cancers in comparison with Stage I and II ones, or in NSCLC in comparison with SCLC either. Thus, the C219 related epitope seems to have a weak implication in the lower chemosensitivity of both advanced stages and NSCLC.

Neoadjuvant chemotherapy of locally advanced non-small cell lung cancer.

Neoadjuvant chemotherapy was tested in non-small cell lung cancer in an attempt to increase the resectability of the tumor and to treat the microscopic metastatic disease known to be responsible for the majority of failures in surgically treated patients. This review deals with published trials. Most of them are feasibility studies in Stage III NSCLC. Obviously, the heterogeneity of eligibility criteria from one study to another prevents general conclusions on the usefulness of neoadjuvant chemotherapy. However, it is possible to conclude that neoadjuvant chemotherapy has an antitumor activity; the majority of the studies report a 60% objective response rate including a significant number of complete responses and a 50% complete resection rate. Neoadjuvant chemotherapy does not increase morbidity after surgery except when it is combined with preoperative radiation therapy. At the time of writing, one Phase III randomized study comparing neoadjuvant chemotherapy followed by surgery with surgery alone has been published. This study concludes that the combined modality treatment improves the survival of patients with locally advanced non-small cell lung cancer. Taken as a whole, the literature deserves further studies to determine the place of neoadjuvant chemotherapy in lung cancer.

Interrelationships between postprandial lipoprotein B:CIII particle changes and high-density lipoprotein subpopulation profiles in mixed hyperlipoproteinemia.

We studied the relationships postprandially between triglyceride-rich lipoprotein (TRL) and high-density lipoprotein (HDL) in 11 mixed hyperlipoproteinemia (MHL) and 11 hypercholesterolemia (HCL) patients. The high and prolonged postprandial triglyceridemia response observed in MHL but not HCL patients was essentially dependent on very-low-density lipoprotein (VLDL) changes. This abnormal response was related to decreased lipoprotein lipase (LPL) activity (-48.7%, P<.01) in MHL compared with HCL subjects. Cholesteryl ester transfer protein (CETP) activity was postprandially enhanced only in MHL patients, and this elevation persisted in the late period (+19% at 12 hours, P<.05), sustaining the delayed enrichment of VLDL with cholesteryl ester (CE). The late postprandial period in MHL patients was also characterized by high levels of apolipoprotein B (apoB)-containing lipoproteins with apoCIII ([LpB:CIII] +36% at 12 hours, P<.01) and decreased levels of apoCIII contained in HDL ([LpCIII-HDL] -34% at 12 hours, P<.01), reflecting probably a defective return of apoCIII from TRL toward HDL. In MHL compared with HCL patients, decreased HDL2 levels were related to both HDL2b and HDL2a subpopulations (-57% and -49%, respectively, P<.01 for both) and decreased apoA-I levels (-53%, P<.01) were equally linked to decreased HDL2 with apoA-I only (LpA-I) and HDL2 with both apoA-I and apoA-II ([LpA-I:A-II] -55% and -52%, respectively, P<.01 for both). The significant inverse correlations between the postprandial magnitude of LpB:CIII and HDL2-LpA-I and HDL2b levels in MHL patients underline the close TRL-HDL interrelationships. Our findings indicate that TRL and HDL abnormalities evidenced at fasting were postprandially amplified, tightly interrelated, and persistent during the late fed period in mixed hyperlipidemia. Thus, these fasting abnormalities are likely postprandially originated and may constitute proatherogenic lipoprotein disorders additional to the HCL in MHL patients.

Hyperalphalipoproteinemia: characterization of a cardioprotective profile associating increased high-density lipoprotein2 levels and decreased hepatic lipase activity.

The aim of the present study was to investigate the high-density lipoprotein (HDL) structural characteristics and metabolism in hyperalphalipoproteinemic (HALP) patients (HDL-cholesterol [HDL-C], 92 +/- 14 mg/dL) with combined elevated low-density lipoprotein-cholesterol (LDL-C) levels (LDL-C, 181 +/- 33 mg/dL). Patients were subjected to a complete cardiovascular examination, including ultrasonographic investigation of carotid arteries. Two HALP profiles were identified according to the HDL2/HDL3 ratio. HALP profile A was characterized in 28 patients by increased HDL2/HDL3 ratio, HDL2b, and lipoprotein (Lp)A-I levels compared with normolipidemic subjects, and HALP profile B, including the 12 remaining patients, was characterized by a HDL2/HDL3 ratio within the normal range and by the increase of all HDL subclasses (HDL(2b,2a,3a,3b,3c)), LpA-I, and LpA-I:A-II levels. With regard to the exploration of carotid arteries, in HALP profile A, 20 patients were free from lesions and eight had only intimal wall thickening. In HALP profile B, only one patient was free from lesions, four had intimal wall thickening, and seven displayed plaques, but none had stenosis. Taking into account the number of patients with plaques within each group, HALP profile A was associated with a low prevalence of atherosclerotic lesions, whereas HALP profile B was less cardioprotective (odds ratio, 77.7 [95% confidence interval, 3.7 to 1,569.7]; P < .0001). For both HALP profiles, cholesteryl ester transfer protein (CETP) deficiency was discarded and activities of phospholipid transfer protein (PLTP) and lipoprotein lipase (LPL) were normal. However, hepatic lipase (HL) activity was significantly decreased in HALP profile A, but within the normal range for HALP profile B. In conclusion, an HALP profile A with a low prevalence of atherosclerosis was characterized by an increased HDL2/HDL3 ratio, HDL2b, and LpA-I levels associated with decreased HL activity.

Direct isolation of labeled low density lipoproteins for the determination of cholesteryl ester transfer protein activity.

The measurement of the activity of cholesteryl ester transfer protein (CETP), is of high clinical interest and this study reports the use of a direct LDL isolation (d-LDL) technique to determine in one step the amount of radiolabeled cholesteryls esters ([3H]-CE) transferred from exogenous HDL3 to LDL, avoiding the conveniences of the usually used ultracentrifugation or precipitation of apo-B containing lipoproteins in the CETP methodologies. The d-LDL technique providing a specific immunoprecipitation of VLDL, IDL and HDL allowed to directly determine the [3H]-CE transferred on LDL (d-[3H]-CE-LDL). Two methodologies were assayed for the CETP activity using either exogenous or endogenous lipoproteins, and the results with the d-LDL technique were compared with those obtained using the ultracentrifugation (u-[3H]-CE-LDL) considered as the reference method. The intra- and inter-assays were similar in both techniques for the two CETP activity assays. Strong positive correlations were established between values obtained with d-[3H]-CE-LDL and u-[3H]-CE-LDL isolation procedures for CETP activities with exogenous or endogenous lipoproteins (r = 0.972; p = 0.0001 and r = 0.965; p = 0.0001 respectively). In conclusion, the d-LDL technique represents an easy and accurate procedure to measure directly, in normotriglyceridemic plasmas, the amount of [3H]-CE transferred from HDL to LDL by the CETP.

'The-skipping' revisited in French: programming saccades to skip the article 'les'.

Three experiments were performed to verify O'Regan's (1979) [Perception & Psychophysics, 25 (6), 501-509] finding that in reading, the eye moves further forward when going towards the word 'THE' than when going towards a three-letter verb. The experiments were performed in French instead of English, and compared the plural article 'les' with different three-letter verbs. It was confirmed that the eye did indeed move about 1.5 letters further in the case of the article 'les'. Further investigation of the phenomenon suggested that the effect was present even when the prior fixation duration was short: Only when prior fixation was around 200 ms or less, and additionally when the eye started from a launch position that was far from the word, was there a suggestion that the 'les'-skipping effect disappeared.