EHT0202 in Alzheimer's disease: a 3-month, randomized, placebo-controlled, double-blind study.

BACKGROUND: EHT0202 (etazolate hydrochloride) is a new compound exhibiting both potential disease-modifying and symptomatic treatment properties in Alzheimer's Disease increasing alpha-secretase activity and sAPP alpha secretion, as well as acting as a GABA-A receptor modulator and as a PDE-4 inhibitor. METHODS: This pilot, randomized, double-blind, placebo-controlled, parallel group, multicentre, Phase IIA study was conducted in 159 randomized patients suffering from mild to moderate Alzheimer's Disease. EHT0202 (40 or 80 mg bid) or placebo was administered as adjunctive therapy to one acetylcholinesterase inhibitor over a 3-month period. This study was designed to assess the clinical safety and tolerability of EHT0202 as a primary objective, with secondary endpoints (cognitive function, daily living activities, behaviour, caregiver burden and global functioning) included to explore clinical efficacy of EHT0202 versus placebo. RESULTS: EHT0202 was shown to be safe and generally well tolerated. Dose-dependent numbers of early withdrawal and central nervous system related adverse events were observed. As expected, since the study was not powered and not designed to show drug efficacy, and except for ratings on the ADCS-ADL scale, no significant differences were seen between treatment groups. CONCLUSIONS: These first encouraging safety results do support further development of EHT0202 in order to assess its clinical efficacy and to confirm its tolerability in a larger cohort of Alzheimer patients and for a longer period.

[Endotracheal intubation under propofol with or without vecuronium]. / Intubation endotrachéale sous propofol avec ou sans vécuronium.

OBJECTIVE: In order to test the hypothesis that under the association propofol-alfentanil-IV lidocaine the trachea could be intubated easily without an additional muscle relaxant, this study compared the intubation conditions when this association was combined or not with vecuronium. STUDY DESIGN: Randomized comparative trial. PATIENTS: The study included 152 young adults classified as ASA physical class I and Mallampati presentation grade 1, randomly allocated either into Vecu+ group or Vécu0 group, depending on whether vecuronium was co-administered or not. METHODS: All patients received midazolam 0.05 mg.kg-1 i.v., one minute before induction. Those of group Vecu0 were given successively within two minutes: alfentanil 0.03 mg.kg-1, lidocaine 1.5 mg.kg-1 i.v. and propofol 2.5 mg.kg-1. Patients of group Vecu+ received similar doses of alfentanil and propofol as well as vecuronium 0.08 mg.kg-1. The endotracheal tube was inserted one minute after induction in the patients of Vecu0 group, and after three minutes in those of the Vecu+ group. During intubation, scores of mouth opening, glottis opening and coughing were established, in order to assess intubation conditions. RESULTS: Similar convenient intubating conditions were obtained in both groups (in 97% of patients in Vecu+ group vs 95% of those in Vecu0 group). In the latter, the glottis opening was less pronounced. CONCLUSIONS: In young healthy adults, without anaesthetic risk (emergency, full stomach) and without foreseen difficult intubation, the endotracheal tube can be inserted in convenient conditions without a muscle relaxant, under the association propofol-alfentanil-lidocaine iv.

[Outcome of transfusion practices in general hospitals in Lorraine]. / Evolution des pratiques transfusionnelles dans les centres hospitaliers généraux de Lorraine.

Authors carried out, in 17 public (non university) hospitals, a retrospective study on evolution of blood transfusion techniques in a french province (Lorraine). In every hospital, they obtained the annual consumption of blood or derivatives prescribed by the anaesthetists. Use of different sparing techniques was noted. All these parameters were connected to the anaesthetic and surgical activities. For statistical study, a Student test was used. Results demonstrate increasing anaesthetic and surgical activities. However the reduction of mean consumption of plasma and red blood cells is not significant. The sparing techniques are not fully used, partly because of too long distances from the blood centres. Blood prescriptions should and could be optimized.

[Hematopoietic growth factor (GM-CSF) after autologous bone marrow transplantation. A randomized, double-blind, multicenter study in 91 cases of non-Hodgkin's malignant lymphomas]. / Facteur de croissance hématopoïétique (GM-CSF) après autogreffe de moelle osseuse. Etude randomisée multicentrique en double aveugle dans 91 cas de lymphomes malins non hodgkiniens.

To a great extent, the risks of autologous bone marrow transplantation are related to neutropenia. Although the efficacy of the recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) on neutrophil recovery has appeared in numerous open trials, only a few randomized studies have hitherto been published. Ninety-one patients with non-Hodgkin's malignant lymphoma treated with ablative chemotherapy followed by purged or unpurged bone marrow transplantation were entered in a placebo-controlled, double-blind randomized study; 44 patients received GM-CSF (E. coli) in doses of 250 micrograms/m2/day, and 47 received a placebo. Treatment was administered daily as continuous infusion started on the day of transplantation and pursued until the absolute number of neutrophils reached 0.5 x 10(9)/l during 7 days or, if this failed, during 30 days. The median time of neutrophil recovery was 14 days in patients on rhu GM-CSF and 21 days in patients on placebo (P < 0.0001). Patients who received a mafosfamide-purged bone marrow also had a rapid neutrophil recovery (median: 16 days versus 20.5 days; P = 0.013). The stay in hospital was shorter in the rhu GM-CSF group (median: 23 days versus 28 days; P < 0.05). No significant difference in the number of days with fever, infections, antibiotics administered and overall survival was detected between the two groups. The main toxicity ascribable to rhu GM-CSF was a capillary leakage syndrome found in 3 patients. Thus, after purged or unpurged autologous bone marrow transplantation rhu GM-CSF significantly reduces the duration of both neutropenia and hospital stay.

Comparison of response rates to the angiotensin-converting enzyme inhibitor ramipril in mild-to-moderate hypertension in a double-blind, parallel-group study and an open single-blind study.

Appropriate clinical trial methodologies in general practice and suitable end points for dose-finding studies are discussed with reference to antihypertensive drugs in general and angiotensin-converting enzyme (ACE) inhibitors in particular. Two clinical studies were conducted with ramipril, a new nonsulfhydryl ACE inhibitor, to identify the minimum effective dose for the management of mild-to-moderate hypertension. Study 1 was a double-blind, parallel-group, randomized design with three treatment groups (placebo and 2.5 and 5 mg of ramipril), and study 2 was an open, single-blind design with individual dose titration from 2.5 to 5 mg of ramipril if the diastolic blood pressure (DBP) was greater than 90 mm Hg after 3 weeks. Response rates and DBP reductions with 2.5 mg of ramipril were similar in both studies, although overall response rates, DBP reductions, and side effect incidence appeared to be greater in the open, single-blind, dose-titration study. It is concluded that study methodology apparently influences efficacy and tolerability.

[Efficacy of Triatec in monotherapy and in combination with Lasilix in a French multicenter study]. / Efficacité du Triatec en monothérapie et en association au Lasilix dans l'étude multicentrique française.

The 770 subjects enrolled into the French multicenter trial of Triatec (ramipril) presented the usual characteristics of moderate hypertension. After a low rate of response to placebo (9.1 p. 100), over half the active treatment patients responded to Triatec 2.5 mg (57 p. 100). Later on, Triatec 5 mg achieved control of half the remaining patients (55.6 p. 100); lastly, among non-responders to that posology, no difference was noted between monotherapy with 10 mg of Triatec, and the combination of 20 mg of Lasilix (furosemide) and Triatec 5 mg (respectively 44.7 p. 100 and 47.4 p. 10 responders). As a whole, more than 90 p. 100 of the patients responded to the proposed treatment plan.

Rapid detection of bacteriuria by laser nephelometry.

A total of 1,002 urine specimens were evaluated by laser nephelometry. This technique was compared with both colony counts, done with a calibrated loop, and serial dilutions. For urine specimens containing between 10(4) and 10(5) bacteria per ml, laser nephelometry detected 75.4% of those detected by colony count and 65.6% of those detected by serial dilution. For specimens where the concentration of bacteria was greater than 10(5) per ml, laser nephelometry detected 95.8 and 92.4% of those detected by colony count and serial dilution, respectively. The mean detection time for bacteriuria varied from 1.57 h for more than 10(5) bacteria per ml to 4.47 h for more than 10(4) bacteria per ml. To determine the number of bacteria according to the voltage growth curve, the passage time at 3 V was used as an index. The mean passage time at 3 V decreased from 5.18 h for fewer than 10(4) bacteria per ml to 1.42 h for more than 10(6) bacteria per ml. The mean passage time at 3 V differed significantly for different concentrations of bacteria. Thus, this index allowed us to predict the number of bacteria in the urine specimens. Laser nephelometry has been used for many years for the immunological determination of proteins; it can now also be considered a tool for rapid screening in bacteriology.

Red blood cell filterability in non-diabetic patients with chronic occlusive arterial disease.

One-hundred and fifty non-diabetic patients with stage II chronic occlusive arterial disease (COAD), were tested for red blood cell filterability (RBF). At the same time, glycaemia, uricaemia, plasma cholesterol and triglycerides, fibrinogen, haematocrit, and white blood cells (granulocytes and lymphocytes) count, mean corpuscular volume, were measured. Thirty healthy people, tested for the same biological parameters, were used as controls. RBF was performed, using the Reid & Dormandy technique, with the same batch of filters (Nuclepore 5 micrometer, No. 54 A8 A25) for patients and controls. Filtration time was expressed in s.ml-1. Values obtained in patients (41.967 +/- 0.889) were significantly different (P less than 0.005) from controls (32.1 +/- 1.329). RBF alteration was correlated (P less than 0.05) with white blood cells count, haematocrit and plasma fibrinogen values. No correlation was observed with other biological parameters.