Detection of antidrug IgG antibodies in patients with adverse drug reactions to amodiaquine

Antidrug IgG antibodies have been detected in some patients receiving amodiaquine (AQ). Antidrug antibodies were detected in 6/7 patients who experienced serious well-defined adverse drug reactions during malaria prophylaxis and in 7/22 patients who received comparable doses of the drug (at least 400 mg weekly x 6) but did not present with clinical adverse drug reactions. In contrast antidrug antibodies were not detected in 7 patients who received the drug for treatment (1.0-1.2 g total over 3 days). The specificity of the IgG response was defined by hapten inhibition experiments (IC50 value for AQ ranged between 0.050 and 0.282 microM) which suggest that the antibody recognised the drug linked to cysteine residues in protein via the 4-hydroxyanilino side chain. The data show that AQ is immunogenic in man and are consistent with the hypothesis that idiosyncratic adverse reactions to the drug have an immunological aetiology.     

The antibacterial component from Cinnamomi Cortex against a cariogenic bacteriumStreptococcus mutans OMZ 176

The methanol extract of Cinnamomi Cortex showed antibacterial action against cariogenic bacterium,Streptococcus mutans OMZ 176. The active principle of the extract was identified to betrans-cinnamaldehyde, which was bactericidal in the minimal inhibitory concentration (MIC) of 100 μg/ml againt the strain. From the results of antibacterial activity of cinnamaldehyde and its derivatives, the acrolein group in the cinnamal-dehyde was elucidated to be an essential element for the activity.     

Indwelling epidural catheters for pain control in gynecologic cancer patients

Seven patients with severe pain caused by an advanced, incurable gynecologic malignancy were treated with an indwelling epidural catheter connected to an implantable subcutaneous port through which morphine was infused. There were few major complications associated with insertion or maintenance of the system. The average usage was 60 days, although the system functioned continuously for 6 months in one patient. Pain distribution in these women ranged from the upper abdomen to the lower extremities. All patients, including one with liver metastases, reported good to excellent pain control with the epidural narcotics. Two subjects with upper abdominal pain occasionally required supplemental oral oxycodone, but the other five patients had adequate pain relief with the epidural system alone. The indwelling epidural system provides excellent analgesia for patients with advanced, incurable gynecologic cancer.     

Synaptic plasticity in the dentate gyrus of aged rats is altered after chronic nimodipine application.

We examined ultrastructural correlates of synaptic plasticity in the hippocampus of young (3 months) vs aged (30 months) Wistar rats and established the effects of the calcium antagonist nimodipine in animals chronically treated from 24 to 30 months. The effects of nimodipine was studied since this compound improves hippocampal neuronal physiology and enhances cognitive function during aging. In the supragranular layer of the dentate gyrus we found a 24% decrease in synaptic density (Nv) in aged animals, while synaptic size (S) was not significantly altered. After nimodipine treatment Nv in aged rats was not significantly different from young adults, thus being significantly increased compared to age-matched controls. The size of synapses was not significantly altered after nimodipine administration. Total synaptic surface area (Sv) in nimodipine-treated animals was significantly increased compared to aged controls, however, Sv remained significantly lower than in young adults. These data indicate that chronic administration of nimodipine enables granular cells in the dentate gyrus to maintain its number of synaptic contacts during the aging process. Furthermore, the presented influence of nimodipine on synaptic plasticity processes may underlie previously reported improved cognitive functioning of aged animals treated similarly with nimodipine.     

Selective inactivation of viruses in the presence of human platelets: UV sensitization with psoralen derivatives.

Inactivation of viruses in blood products requires that the method employed display selectivity in its action for viral elements while not affecting the biological entity of interest. Several methods have been developed for the treatment of human plasma or products derived from human plasma. An effective technique for the treatment of the cellular components of blood has been lacking, in part due to the inability to develop agents capable of selectively targeting viral agents in the milieu of cellular material. In this paper, we examine the behavior of a group of viral sensitizers designed to be added to cellular samples and be activated upon exposure to UVA light. Upon activation, these agents are capable of disrupting nucleic acids of the virus in a manner that renders them inactive for proliferation. The selectivity observed in this inactivation is determined by the chemical structure of the sensitizer, which can be varied to increase viral killing capacity while diminishing collateral damage to cellular and protein constituents.     

Effects of inotropes on human leucocyte numbers, neutrophil function and lymphocyte subtypes

We have investigated the effects of inotropes with different adrenergic receptor specificity on differential white cell count, lymphocyte subtypes and neutrophil function in healthy volunteers. Six healthy, male volunteers were enrolled into this randomized, placebo-controlled pilot study. Each volunteer was studied on four separate occasions during a 2-h infusion of various agents, and for 2 h after stopping the infusion. The agents investigated were adrenaline 0.1 microgram kg-1 min-1, dobutamine 5 micrograms kg-1 min-1, dopexamine 2 micrograms kg-1 min-1 and 5% glucose 0.5 ml kg-1 h-1. Venous blood was sampled at 0, 30, 120 and 240 min. Haemodynamic monitoring was continued throughout the study. Full blood count, white cell differential count and enumeration of lymphocyte subtypes were performed. Neutrophil function tests included chemoluminescence, and assessment of neutrophil chemotaxis, phagocytosis and adhesion. The Wilcoxon signed rank test was used to compare differences between placebo and active drugs at each time compared with baseline. There was a significant increase in white cell count, lymphocyte count and neutrophil count with adrenaline, and a small but significant decrease in these variables with dobutamine and dopexamine. These changes were also apparent for absolute CD3+, CD4+ and CD8+ lymphocyte counts. Neutrophil respiratory burst in response to f-methionyl-leucyl-phenylalanine increased significantly only with adrenaline at 30 min (P = 0.046). There were no other significant changes in tests of neutrophil function. Infusion of inotropes was associated with changes in white cell numbers, lymphocyte subtypes and neutrophil respiratory burst. In healthy volunteers, adrenaline had effects different from those of dobutamine and dopexamine. The clinical relevance of such effects requires further investigation in critically ill patients.      

Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [¹³N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127±31 ml·min^–1·100 g^–1; group B, 124±30 ml·min^–1·100 g^–1 normal subjects, 105±21 ml·min^–1·100 g^–1 (groups A and B vs normals,P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20±0.23; group B, 1.24±0.22; normal subjects, 1.23±0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71±0.67; group B, 2.77±1.29; normal subjects, 2.91±1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1±4.5 vs 17.0±3.0,P<0.05). In group B (coefficient of variation 19.4±3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.     

Molluscum contagiosum occurring in an epidermal cyst--report of 3 cases.

We present three unusual cases of molluscum contagiosum occurring in epidermal cysts. All of them are asymptomatic, elevated, oval nodules diagnosed clinically as epidermal inclusion cyst or prurigo nodularis. Histology showed true epidermal cysts containing molluscum bodies throughout the cyst wall and some type of laminated material within the cyst itself. The lesion, in all three cases developed in the pubic area of young adult men.     

Regional analysis of 5-HT1A and 5-HT2 receptors in the fawn-hooded rat.

The Fawn-Hooded strain of rats exhibits a hemorrhagic disorder, known as platelet storage pool deficiency. In addition to the platelet dysfunction, there is an altered response to certain serotonin drugs. To assess the characteristics of the binding to 5-HT1A and 5-HT2 receptors in this strain, regions of the brain from Fawn-Hooded, Sprague-Dawley and Wistar male rats were examined. The drug [3H]8-OH-DPAT was used to label 5-HT1A receptors and the Kd values for frontal cortex, hippocampus, striatum, hypothalamus and brainstem were similar in all three strains of rat. As with the 5-HT1A receptors, no differences were observed in the Kd values for 5-HT2 receptors, in any of the regions examined, among the three strains. However, the Bmax for the binding of [3H]8-OH-DPAT in the striatum and brainstem of Fawn-Hooded rats was less than in the Sprague-Dawley and Wistar animals. Furthermore, 5-HT2 receptors displayed a greater Bmax value in the striatum and in the frontal cortex of Fawn-Hooded animals, compared to Sprague-Dawley and Wistar rats. These differences in receptors are consistent with previous studies in which Fawn-Hooded rats were found to have altered serotonergic function, relative to Wistar and Sprague-Dawley animals.