Double-blind controlled clinical study of the efficacy and tolerability of diclofenac-N-(2-hydroxyethyl)-pyrrolidine lecithin gel compared with diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel in patients with peri and extraarticular inflammatory diseases

To evaluate the efficacy and tolerability of the new diclofenac-N-(2-hydroxyethyl)-pyrrolidine lecithin gel (DHEP lecithin gel, with 1.3% DHEP and 2.4% lecithin) compared with the efficacy and tolerability of diclofenac-N-(2-hydroxyethyl)-pyrrolidine gel (DHEP gel) in peri and extraarticular inflammatory states, a controlled, randomized, double-blind clinical study was conducted. Two groups of 50 patients each were enrolled and were given one of the two different formulations with a slight massage on the painful area three times a day for 10 consecutive days. Patients received a self-evaluation notebook in which to record daily assessment of spontaneous pain (Huskisson's visual analogue scale). On days 0, 3 and 10, the patients were visited by the investigator. All patients completed the study. The assessment of spontaneous pain showed that although pain decreased in both groups, the decrease was more marked in patients taking DEHP lecithin gel and that it reached a statistically significant difference at days 5, 6, 7 and 8. This decrease was also confirmed by assessments on the ordinal scale. Although periarticular swelling disappeared in both groups, swelling severity decreased sooner in patients taking DHEP lecithin gel. The efficacy and safety of both treatments was judged to be good or excellent by 70% of the patients in each group. The efficacy of the active principle, pyrrolidine salt, is confirmed. Moreover, the formulation containing lecithin passes through the skin lipid barrier more easily than the formulation without lecithin and is as valid as the other in the therapy of rheumatic disorders. Finally, DHEP lecithin gel preparation has a quicker therapeutic action on symptoms, such as spontaneous pain and local swelling, than DHEP gel.     

Volumetric rendering techniques: applications for three-dimensional imaging of the hip

Volumetric rendering is a new approach to three-dimensional (3D) imaging that overcomes many of the drawbacks of currently available surface-rendering systems. Its application on the Pixar Imaging System in two cases of acetabular fracture was assessed to illustrate the features of the technique. The fast-computing architecture and large memory of this system allow rapid generation of a series of high-quality 3D images in each plane of rotation (x or spinal axis, z or somersaulting axis) that can be viewed as independent static images or as an animated real-time video loop. Editing to remove the normal contralateral hemipelvis enhances appreciation of acetabular abnormalities. Every pixel of computed tomographic data is preserved, allowing representation of both soft tissue and bone as translucent overlap. The presentation of data also allows detection of subtle abnormalities and features and minimizes the artifact generation common in surface-rendered images.     

Uterine artery Doppler at 11-14 weeks of gestation in chromosomally abnormal fetuses.

OBJECTIVE: To determine whether the major chromosomal abnormalities are associated with impaired placentation in the first trimester of pregnancy. METHODS: This was a prospective study of 692 singleton pregnancies undergoing fetal karyotyping at 11-14 weeks of gestation. Uterine artery Doppler was carried out and the mean pulsatility index was calculated just before chorionic villus sampling. RESULTS: The fetal karyotype was normal in 613 pregnancies and abnormal in 79, including 39 cases of trisomy 21, 11 of trisomy 18, 11 of trisomy 13, eight of Turner syndrome and 10 with other defects. There were no significant differences in the median value of uterine artery mean PI between any of the individual groups. Although in the combined group of trisomy 18, trisomy 13 and Turner syndrome fetuses, the median pulsatility index (1.60) was significantly higher than in the chromosomally normal group (median pulsatility index, 1.51; P = 0.021), in the majority of abnormal fetuses (24 of 30) mean pulsatility index was below the 95th centile of the normal group (mean pulsatility index, 2.34). There was no significant association between uterine artery mean pulsatility index and fetal nuchal translucency thickness or fetal growth deficit. CONCLUSIONS: The high intrauterine lethality and fetal growth restriction associated with the major chromosomal abnormalities are unlikely to be the consequence of impaired placentation in the first trimester of pregnancy.     

Triptans: the experience of a clinical pharmacologist in clinical practice

Despite the pharmacokinetic differences among triptans and the variety of ways of administration, the clinical differences in every day use of these drugs lack in an accepted decisional tree. In fact, there are a number of comparative trials showing conflicting results with regard to efficacy, onset of action, safety and recurrence incidence. That means that the patient’s preference probably is the main criterion for choosing one triptan vs. others. This point of view is probably correct considering also that the main cause of therapy failure is noncompliance. A good migraine care strategy requires a balance in what the patient views as satisfactory, a reasonable compromise between efficacy and tolerability, and a careful follow–up. Improvement in compliance should be the main and more immediate goal for the treatment of migraine attacks.     

Cervical length at 23 weeks in triplets: prediction of spontaneous preterm delivery.

OBJECTIVES: To establish the distribution of cervical length at 23 weeks of gestation in triplet pregnancies and to examine the relation to preterm delivery before 33 weeks. METHODS: Cervical length was measured by transvaginal sonography at 23 (range 22-24) weeks of gestation in 43 triplet pregnancies. The distribution of cervical length was determined and the relationship between cervical length and the rate of spontaneous preterm delivery before 33 weeks was calculated. RESULTS: The cervical length distribution was skewed to the left with a median of 34 mm. The rate of spontaneous labor and delivery before 33 weeks increased exponentially with decreasing cervical length at 23 weeks from 8% at 36-48 mm, to 11% at 26-35 mm, 33% at 16-25 mm and 67% at 15 mm or less. Cervical length was < or = 30 mm, < or = 25 mm and < or = 15 mm in 37%, 16% and 8% of cases, respectively, and the corresponding sensitivities in the prediction of spontaneous delivery before 33 weeks were 67%, 50% and 33%. CONCLUSIONS: In triplet pregnancies, measurement of cervical length provides a useful prediction of risk for spontaneous early preterm delivery.     

Classical conditioning of meaning--I. A replication and higher-order extension

The meaning that individuals associate with verbal stimuli may be modified by using classical conditioning procedures. Clinically, such procedures may be used to modify a client's maladaptive associations. The current research investigated the existence and generalizability of this phenomenon by attempting to replicate Staats and Staats' (1957) language conditioning effect and then extent it to a second-order classical conditioning situation (CS1----UCS then CS2----CS1). Such higher-order conditioning would suggest that several different but related maladaptive associations can be modified simultaneously. Significant conditioning was obtained to the CS1, particularly for aware subjects, but no conditioning occurred to the CS2.     

Analysis of protease inhibitor combinations in vitro: activity of lopinavir, amprenavir and tipranavir against HIV type 1 wild-type and drug-resistant isolates

Background: Despite the increasing number of antiretroviral compounds, the number of useful drug regimens is limited owing to the high frequency of cross-resistance. PATIENTS AND METHODS: We studied in vitro two-drug combinations using three protease inhibitors (PIs), tipranavir, amprenavir and lopinavir, on isolates (003 and 004) derived from patients with resistance to multiple PIs compared with the drug-susceptible isolate 14aPre in peripheral blood mononuclear cells. Drug interactions were determined by median dose-effect analysis, with the combination index calculated at several inhibitory concentrations (IC). RESULTS: In 14aPre experiments, the combination tipranavir + lopinavir demonstrated synergy at low concentrations (IC(50)), an additive effect at IC(75) and antagonism at IC(90)-IC(95); tipranavir + amprenavir were antagonistic at all concentrations except IC(95), where they were synergic; and the lopinavir + amprenavir combination was always antagonistic. In 003 and 004 infections, tipranavir + lopinavir and tipranavir + amprenavir combinations were antagonistic, and lopinavir + amprenavir were synergic, at all concentrations, with the exception of being additive at IC(95). CONCLUSIONS: Our in vitro experiments did not show any advantage in combining second generation PIs as a therapeutic strategy in naive or multi-treatment failure subjects, with the exception of tipranavir + amprenavir at IC(95) in infections by a wild-type isolate.