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.     

Blood flow acceleration in the carotid and brachial arteries of healthy volunteers: respective contributions of cardiac performance and local resistance

Summary— The influence of local resistance and cardiac performance on peripheral blood acceleration was investigated in 14 healthy male volunteers. Steady and pulsatile flow was studied in the brachial and in the common carotid arteries, ie, two territories that exhibit marked differences in resistive characteristics. Instantaneous blood velocity (V), mean blood velocity (V_m) and artery diameter (D) were evaluated at rest by an ultrasonic range-gated pulsed Doppler flowmeter using a double transducer probe, thus allowing the calculation of mean blood flow (Q). Mean local resistance (R) was obtained by dividing the mean arterial pressure by Q. The peak value of the local acceleration of the blood was obtained by computer-assisted calculation of the first derivative of instantaneous blood velocity (G_max = +dV/dt_max). Peak aortic blood acceleration (GAo) was simultaneously measured from the suprasternal notch using a pulsed Doppler velocity meter. In the brachial and the common carotid arteries, G_max was of a similar magnitude (551 ±30 and 555 ± 44 cm/s², respectively) despite major differences in the respective D, V_m, Q and R values. In neither artery was there a relationship between G_max and either resting Q or R. At the brachial artery level, G_max was positively related to GAo ( r = 0.79, P = 0.0008). At the common carotid artery level, there was a weak, although non significant relationship between G_max and GAo ( P = 0.08). Our results indicate that the local acceleration of peripheral blood flow in the brachial artery is related rather to upstream central impulse than to downstream hemodynamics, and suggest some regional differences in the hemodynamic determinants of the local acceleration of peripheral blood flow.     

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.     

Iotrol versus metrizamide in lumbar myelography: a double-blind study

In a prospective, randomized, double-blind study, 49 patients underwent lumbar myelography using iotrol (24 patients) or metrizamide (25 patients). The diagnostic imaging adequacy of iotrol was comparable with that of metrizamide. After iotrol myelography, adverse reactions were fewer, less severe, and of shorter duration than were those following metrizamide myelography. Thirteen of 24 patients (54%) receiving iotrol reported some adverse reactions compared with 24 of 25 patients (96%) receiving metrizamide. Five moderate and one severe adverse reaction occurred in the group receiving iotrol. Fourteen moderate and eight severe adverse reactions occurred in the group receiving metrizamide. Thirty-eight patients underwent electroencephalography both before and after myelography (19 iotrol and 19 metrizamide). None of the EEGs obtained after iotrol myelography changed from baseline, while seven of the EEGs obtained after metrizamide myelography showed changes from baseline. Iotrol was judged superior to metrizamide as a contrast medium in this patient population.     

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.