Evaluation of the central anticholinergic activity of antidepressants. Comparison of two experimental methods

The anticholinergic effect of atropine, imipramine, clomipramine and metapramine was evaluated on oxotremorine induced trembling in the mouse as well as on contractions of the isolated guinea pig ileum induced by electrical stimulation of the mesenteric plexus. The ED 50 and IC 50 which expressed the anticholinergic activity of these substances, were found to be identifically distributed for both methods. Activity, in decreasing order was found to be: atropine much greater than imipramine greater than clomipramine greater than metapramine. There was a good correlation between results from the two methods (r = 0.97). The method using the stimulated guinea pig ileum would therefore seem suitable for characterisation of potential anticholinergic activity of a molecule.     

Group versus individual treatment in obsessions without compulsions

The principal goal of the current study was to compare the efficacy of two treatment formats, group and individual, of an empirically proven manualized cognitive–behavioural treatment (CBT) package, for obsessions without overt compulsions. It was hypothesized that individualized treatment would be more effective both in terms of post-treatment group mean improvement and end state functioning. A secondary goal was to assess the relationship between cognitive and behavioural change during treatment and link it to symptom change. Both group and individual CBT format produced a significant clinical change, but as expected individual treatment produced the greater change in symptoms and in obsessional belief. Also, the individual format showed a clear superiority over the group format in the reduction of anxiety and depression. Severity of OCD symptoms showed little relationship with strength of obsessional beliefs at the start of treatment, but change in beliefs was strongly correlated with behavioural improvement post-treatment. The results of the study suggest that the impact of a group format may lie in the value of shared social support and motivational effect of peer feedback, but at the expense of individualized targets. Copyright © 2005 John Wiley & Sons, Ltd.     

Functionalization of poly(methyl methacrylate) by free radical polymerization, 1. Transfer with functional thiols

Chain transfer constants (C_tr) for three phosphonated thiols in methyl methacrylate (MMA) polymerization at 60°C were determined from measurements of the degree of polymerization. These thiols were: diethyl 2-mercaptoethyl phosphate ( 1 ), diethyl 2-mercaptoethylamidophosphate ( 2 ), and tetraethyl mercaptomethylethylene bis(phosphate) ( 3 ). Transfer efficiencies of the thiols were found to be dependent upon their structures. The C_tr value of thiol 2 with MMA was the lowest in the present series, which can be attributed to a possible charged tautomeric form which eventually may reduce the electron density on the thiol, thus rendering the chain transfer reaction with the PMMA radical less feasible. C_tr values of thiol 1 were evaluated at 55, 60, 65, 70 and 75°C. This thiol behaves as an “azeotropic” transfer agent for MMA at 96°C.     

Phenotypic heterogeneity associated with defective apolipoprotein B-100 and occurrence of the familial hypercholesterolemia phenotype in the absence of an LDL-receptor defect within a Canadian kindred

Of 163 individuals with a diagnosis of heterozygous familial hypercholesterolemia (FH), only one subject was found to be positive for familial defective apo B-100 (FDB). The eight-member kindred ascertained through this subject who presented with both a clinical phenotype of FH and the FDB apo B-100 (Arg₃₅₀₀→-Gln) mutation was studied. Plasma lipid and lipoprotein profiles, apo E phenotypes, apo B gene markers at the 3′ hypervariable region and LDL-receptor haplotypes (ApaLI, PvuII, NcoI), were determined, together with LDL-receptor activity on freshly isolated blood lymphocytes. The FDB mutation, present in four relatives, was associated with three different phenotypes: FH and severe hypercholesterolemia, moderate hypercholesterolemia and normolipidemia. The FH phenotype occurred in the absence of any functional LDL-receptor defect. In homozygotes for the absence of the PvuII cutting site who had the apo B mutation, LDL-cholesterol levels were low in the presence of the apo E3/2 phenotype and high in the presence of the apo E4/4 phenotype. None of the major known environmental influences accounted for the wide range of variation in LDL-cholesterol among the affected members. Further observations in the spouse and offspring of the normolipidemic FDB subject confirmed the association of apo E4, the FDB mutation and the PvuH(-/-) genotype with high cholesterol levels. It is concluded that the phenotypic expression of the FDB mutation may vary widely as a function of the genetic environment within a family. The presence of phenotypic heterogeneity among individuals with the same apo B mutation may result from epistatic interaction of the apo B locus with genetic factors regulating cholesterol homeostasis, including possible involvement of the apo E and the LDL-receptor gene loci. This study also confirms that the clinical diagnosis of FH is not necessarily associated with an LDL-receptor defect.     

The relationship of drinking and birth outcome in a US national sample of expectant mothers

Alcohol consumption by pregnant women and birth outcome were studied in 9953 livebirths, 3309 fetal deaths and 5332 infant deaths from the 1988 National Maternal and Infant Health Survey. In crude analyses, race, age, mother's education, prenatal care, parity, low birthweight, gestational age, smoking and alcohol consumption during pregnancy were significantly related to the occurrence of fetal deaths and infant deaths. Among women having livebirths, race, age, mother's education, prenatal care, prematurity, gestational age, smoking and alcohol consumption during pregnancy were significantly related to having a low birthweight baby (< 2500 g). In this group, women who drank more during pregnancy also smoked more, were younger and less educated than women who drank at lower levels or not at all. The relationship of alcohol consumption during pregnancy and infant birthweight for those women having livebirths was studied using multivariable linear regression. The results indicated that race, mother's education, baby's sex, parity, mother's height, mother's body mass index and smoking, but not alcohol consumption, were significantly related to birthweight. Multivariable logistic regressions were performed for the occurrence of low birthweight, fetal death and infant death. The effect of alcohol was significant in all these analyses. These results indicate that alcohol has an important relationship with birth outcome, but that for the drinking reported in this study, the alcohol effect on mean birthweight is small relative to that of other risk factors, accounting for the non-significant result in the multiple linear regression.     

Rapid combined genotyping of factor V, prothrombin and methylenetetrahydrofolate reductase single nucleotide polymorphisms using minor groove binding DNA oligonucleotides (MGB probes) and real-time polymerase chain reaction.

Risk factors for cardiovascular diseases and venous thromboembolism involve both acquired and hereditary conditions. Among the latter, mutations in genes coding for coagulation factors (factor V Leiden [Arg506Gly], G20210A in the 3'-untranslated region of factor II ) and variant C677T of the methylenetetrahydrofolate reductase (MTHFR ) are often involved and co-inherited. These three factors were genotyped simultaneously in the same 96-well plate, using a real-time polymerase chain reaction (PCR) Taqman assay and minor groove binding DNA oligonucleotides (MGB probes). While primers and MGB probes matched their corresponding single nucleotide polymorphism (SNP), the real-time MGB program was identical for each target gene. Homozygous wild-type (WT; -/-), heterozygous (+/-) or homozygous (+/+) variants (n = 362) were selected for factor V (n = 115, with -/-, 40; +/-, 40; +/+, 35), factor II (n = 122, with -/-, 60; +/-, 60; +/+, 2), and MTHFR (n = 120, with -/-, 40; +/-, 40; +/+, 40), according to the results of conventional PCR-restriction fragment length polymorphism (PCR-RFLP), but the allelic discrimination was performed blind. Results of the real-time MGB and PCR-RFLP assays were identical. This new assay was easy and fast with high throughput, without risk of molecular carryover, and cost-effective for laboratories utilizing the Taqman or related fluorescence reading methods. These advantages make it particularly suitable for large-scale combined genotyping of several polymorphisms in the routine setting.     

Concomitant and discriminatory validity of the Adolescents' Fear of Dental Treatment Cognitive Inventory

The revised edition of the Inventaire cognitif de la peur des traitements dentaire pour adolescent(e)s [Adolescents' Fear of Dental Treatment Cognitive Inventory] (ICPTD-A) was administered to 38 subjects chosen at random and to nine subjects chosen with an obvious dental phobia problem. Its concomitant validity was established by relating the ICPTD-A scores to those of a behavioral test. The Pearson correlation coefficients that were thus obtained were -0.66 for the general population and -0.87 for the population suffering from dental phobia. The discriminatory validity was then established with a repeated measurement variance analysis based on the scores of the dental phobics after the administration of a recognized psychological treatment program intended to reduce their phobia. The results have shown a statistically significant difference between the experimental and control groups as well as a significant difference between pre- and posttreatments. The authors have therefore concluded that the ICPTD-A is a valid tool for the assessment of dental phobia in 12-15-year-old adolescents.