Elevation of cell adhesion molecule immunoreactivity in the anterior cingulate cortex in bipolar disorder.

BACKGROUND: Neuroimaging reports of increases in signal hyperintensities in white and deep gray matter and other work indicate that there might be an inflammatory response in affective disorders. METHODS: The microvascular immunoreactivity of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 was measured with image analysis in postmortem tissue from the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) from 15 unipolar and 15 bipolar subjects and compared with each other and with 15 subjects with schizophrenia and 15 control subjects. RESULTS: Intercellular adhesion molecule-1 immunoreactivity in gray and white matter of the ACC in bipolar subjects was increased compared with control subjects (gray: p =.001; white: p <.001) and schizophrenic subjects (gray: p =.016; white: p =.025) and modestly increased in white matter compared with unipolar subjects (p =.049). No such differences were found in the DLPFC. CONCLUSIONS: These findings are consistent with the presence of an inflammatory response in the ACC in bipolar disorder.     

A new method for application of force to cells via ferric oxide beads

 We describe a new method that uses straightforward physics to apply force to substrate-attached cells. In this method, collagen-coated magnetic ferric oxide beads attach to the dorsal surface of cells via receptors of the integrin family, and a magnetic field gradient is applied to produce a force. In this paper we present a complete characterization of the method in a configuration that is easy to use, in which a permanent magnet provides a fairly uniform gradient over a relatively large area. This allows a fairly uniform average force that can be controlled in magnitude, direction, and duration to be applied to a large number of cells. We show how to determine the applied force per cell by measuring the force per unit volume of magnetic bead, the distribution of bead diameters, and the distribution of beads per cell. We also show how to calculate the force per unit volume of bead in a three-dimensional region near the permanent magnet on the basis of field measurements, and present results for three of the magnets. An upward force applied to fibroblasts by this method produces a measurable time-dependent increase in attachment of cytoskeletal actin filaments to the force application points, and an increase in actin cross-linking. This is accompanied by an actin-dependent retraction of the force-induced upward movement of the dorsal surface of the cells. Received: 27 February 1997 / Received after revision: 10 August 1997 / Accepted: 1 September 1997     

Family physicians' perceptions of academic detailing: a quantitative and qualitative study

Background  

The efficacy of academic detailing in changing physicians' knowledge and practice has been the subject of many primary research publications and systematic reviews. However, there is little written about the features of academic detailing that physicians find valuable or that affect their use of it. The goal of our project was to explore family physicians' (FPs) perceptions of academic detailing and the factors that affect their use of it.     

Difficulties using the Franco-Italian Glossary in assessing toxicity of cervical cancer treatment

Shakespeare TP, Ferrier AJ, Holecek MJ, Jagavkar RS, Stevens MJ. Difficulties using the Franco-Italian Glossary in assessing toxicity of cervical cancer treatment. Int J Gynecol Cancer 1998; 8: 51–55
We assessed the toxicities of patients treated for cervical cancer using the revised Franco-Italian Glossary (FIG). A total of 69 separate complications were appraised in 47 patients; however, only 43.5% of these side-effects could be accurately graded. In all, 56.5% of toxicities could not be scored for a variety of reasons: (1) the FIG does not account for all possible complications of cervical cancer treatment; (2) some important toxicities are regarded as too minor to be graded; (3) subjective assessment of some side-effects did not allow consensus to be reached when assigning a grade; (4) we could not accurately score toxicities using the FIG in a retrospective manner. Previous studies utilizing the FIG retrospectively have noted few problems with its use, with no indication of the number of toxicities unable to be graded. In view of the inability to grade the majority of complications in the present study in an accurate manner, we conclude that the revised FIG requires detailed data that are best collected prospectively and that several minor modifications of the glossary should be considered. Results of studies using the glossary retrospectively should be viewed with caution.     

Electrophysiological effects of amrinone and milrinone in an isolated canine cardiac tissue model of ischemia and reperfusion

The purpose of this study was to determine if amrinone or milrinone after the electrophysiological responses of canine ventricular tissues to "ischemia" or reperfusion. Isolated canine Purkinje tissue-papillary muscle preparations were studied using standard microelectrode techniques. Tissues were superfused for 10 min with a solution that mimicked ischemia (hypoxia, acidosis, elevated lactate levels and zero substrate). Reperfusion with normal Tyrode's solution was then instituted for 60 min. Next, tissues were equilibrated with amrinone (5.3 X 10(-4) M) or milrinone (2.5 X 10(-4) M) for 15 min and the protocol was repeated with drug in all solutions. Without drug, ischemic conditions resulted in moderate depolarization of Purkinje and muscle tissues. Reperfusion caused a rapid hyperpolarization in Purkinje tissue. This was followed by a phase of mild depolarization associated with enhanced pacemaker activity. All preparations recovered by 45 min of reperfusion. With amrinone or milrinone present, the changes in membrane potential induced by conditions of ischemia and reperfusion were not different from control. However, an early phase of very rapid ectopic activity was seen during reperfusion with amrinone or milrinone. This ectopic activity had a constant cycle length during the pauses in stimulation. However, irregular patterns of spontaneous and driven beats were observed when electrical stimulation was superimposed on the ectopic activity. Amrinone and milrinone also increased pacemaker activity in Purkinje tissue but this occurred later in reperfusion. This study demonstrates that amrinone and milrinone sensitize isolated canine ventricular tissues to the arrhythmogenic effects of reperfusion. The mechanism underlying the arrhythmic activity elicited by the bipyridines is not clear, but may involve re-entry or abnormal automaticity.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

Selective impairment of paired associate learning after administration of a centrally-acting adrenergic agonist (clonidine)

Eight normal volunteers had IV infusions of 200 g clonidine (a centrally-acting adrenergic agonist which reduces noradrenaline release), and saline in a double-blind cross-over design. Clonidine reduced subjective estimates of arousal but did not affect performance on the Digit Symbol Substitution Test. Clonidine impaired pairedassociate learning, but it did not affect performance on a number of measures of short and long term memory. The findings suggest either 1) that there is a specific (adrenergic) mechanism involved in the acquisition of novel associations, but not in other types of learning, or 2) that paired associate learning is more vulnerable than other learning tasks to disruption of adrenergic transmission.