Pathways linking major depression and immunity in ambulatory female patients

OBJECTIVES: The goals of this study were to investigate whether depression is associated with cellular immunity in ambulatory patients and to identify neuroendocrine and behavioral pathways that might account for this relationship. METHODS: We studied 32 women who met Diagnostic and Statistical Manual of Mental Disorder, fourth edition, criteria for major depressive disorder and 32 healthy female control subjects. The groups were matched for age and ethnicity. None were taking medication, and all were free of disease involving the immune system. RESULTS: Depressed subjects had reduced proliferative responses to the mitogens concanavalin A and phytohemagglutinin compared with control subjects. Natural killer cell activity was reduced among older depressed subjects but enhanced among younger depressed subjects. Although depression was associated with elevated circulating levels of norepinephrine and estradiol, these hormones could not account for the immunologic differences between depressed and control subjects. Depression was also associated with greater tobacco and caffeine consumption, less physical activity, and poorer sleep quality. Mediational analyses were consistent with physical activity acting as a pathway through which depression was associated with reduced lymphocyte proliferation. CONCLUSIONS: Ambulatory patients with mild to moderately severe depression exhibit reduced mitogen-stimulated lymphocyte proliferative responses and altered natural killer cell cytotoxicity. The relationship between depression and proliferative responses may be mediated by physical activity.     

Contribution of erythrocytes to thrombin generation in whole blood

Thrombin generation (TG) initiated by diluted tissue-factor was investigated in whole human blood, in platelet-rich plasma (PRP), in platelet-poor plasma (PPP), and in PPP supplemented with red blood cells (RBCs). TG was characterized by the lag time preceding the thrombin burst and by the endogenous thrombin potential (ETP). RBCs at normal haematocrit were found to influence the lag time to the same extent as platelets. When TG was carried out in PRP or in PPP + RBCs, both the ETP and lag time were dependent on the platelet count or on the haematocrit, but the shapes of the dose-response curves were different. The inhibition of TG in PPP+ RBCs by two direct thrombin and factor Xa inhibitors: hirudin and DX 9065A, and two antithrombin III (AT)-dependent anticoagulants: heparin and SR 90107A was found to be similar to that previously described in PPP and in PRP: hirudin and DX 9065A only delayed TG whereas heparin and SR 90107A both delayed and decreased TG. FACscan analysis following labelling with FITC-annexin V or with phycoerythrin-labelled antiglycophorin A of samples taken in the course of TG initiated in PPP + RBCs showed that no significant haemolysis occurred and revealed that 0.51+/-0.075% (mean +/- sem, n = 3) of RBCs steadily exposed procoagulant phospholipids on their outer surface throughout the TG course. Furthermore, incubation of factors Xa and Va with washed RBCs sampled during TG in PPP +RBCs resulted in a significant and constant prothrombinase activity. Taken together, these data show for the first time that normal RBCs may participate in the haemostatic process through exposure of procoagulant phospholipids.     

Laboratory monitoring of pentasaccharide in a dog model of hemodialysis

Varying dosages of pentasaccharide (400-800 nmol/kg) were compared to a 250-U/kg single bolus dosage of unfractionated heparin (UFH) in a dog model of hemodialysis. Several laboratory assays were used to monitor the effects of pentasaccharide and UFH. The pentasaccharide did not produce any anticoagulant effects as measured by the activated partial thromboplastin time. However, in the anti-Xa chromogenic assay and the Heptest assays, there was a dose-dependent prolongation after pentasaccharide administration. In the group of dogs administered 800 nmol/kg of pentasaccharide, there was a 50% decrease in the thrombin antithrombin (TAT) complex level after 60 minutes on dialysis. In the UFH-treated dogs, wide variations in assays were observed. There was a marked elevation in the activated partial thromboplastin time and Heptest assays up to 6 hours after UFH administration. Both anti-Xa and anti-IIa activity was measured up to 4 hours. In the TAT assay, UFH was found to have a stronger effect in suppressing the formation of TAT in comparison to the pentasaccharide. These results suggest that pentasaccharide can be used as a replacement for UFH in a dog model of hemodialysis to keep the dialysis circuit patent. In addition, the anti-Xa-based assays such as the Heptest and the chromogenic anti-Xa assays can be used to monitor the effects of pentasaccharide in this model.     

Discriminating mirror symmetry in foveal and extra-foveal vision

The ability to discriminate perfect from imperfect mirror symmetry was examined at the fovea and at eccentricities out to 10 degrees in the nasal visual field. A 2-AFC method of constant stimuli was employed in which a bilaterally symmetric pattern was presented in one interval and a degraded version of this symmetric pattern in the other. The subject's task was to decide which interval contained the perfectly symmetric pattern. Pattern size was varied by changing the viewing distance. Probit analysis revealed the degree of asymmetry corresponding to 75% correct performance. Given sufficient size scaling, perfectly symmetric stimuli can be discriminated from degraded symmetric stimuli in extra-foveal vision. Spatial scaling with an E2 value similar to that for positional acuity was successful in removing the eccentricity dependence for the task.     

Measurement of in vitro cellular pharmacokinetics of 5-fluorouracil in human and rat cancer cell lines and rat hepatocytes using a flow-through system

Summary A flow-throught system was used to study the cellular pharmacokinetics of 5-fluorouracil (5-FU) in four human cell lines (squamous-cell carcinoma HEp-2, colon carcinoma WiDr, hepatoma Hep G2, and breast carcinoma MCF-7) as well as in the rat hepatoma H35 cell line and in freshly isolated rat hepatocytes. The system made it possible to restrict the decrease in the concentration of 5-FU in the medium, to keep the volume in which the metabolites accumulated relatively small, and to study the dynamics of a response during and after a change in the composition of the eluent. Clearance of 5-FU from the eluent was achieved predominantly (>95%) by its catabolism to dihydrofluorouracil in the tumor cell lines and to 2-fluoro--alanine in the hepatocytes. Not only rat hepatocytes but also HEp-2 cells showed relatively high clearance values. A concentration-dependent 5-FU elimination was observed, indicating saturation of 5-FU elimination according to Michaelis-Menten kinetics (K_m 14–22 M). The maximal velocity (V_max) values ranged from 0.025 to 0.13 nmol 5-FU/10⁶ cells per minute. For HEp-2 cells, high-concentration pulse injections of 5-FU, thymine, uridine, or uracil immediately led to a reduction in 5-FU conversion, followed by recovery within 5 min. The flow-through system proved to be adequate for the study of the non-linear pharmacokinetics of 5-FU in different intact cells and for the comparison of various manipulations of these pharmacokinetics.Abbreviations 5-FU 5-fluorouracil - FUR 5-fluorouridine - F-DHU dihydrofluorouracil - F--ala 2-fluoro--alanine - F-UPA -fluoroureidopropionic acid - HEPES 4-(2-hydroethyl)-1-piperazine-ethane sulfonic acid - MEM modified minimal essential medium - HBSS Hanks' balanced salt solution - HPLC high-performance liquid chromatography Supported by grant IKA 87-16 from the Netherlands Cancer Foundation. One author (G. J. P.) is the recipient of a senior research fellowship from the Royal Netherlands Academy of Arts and Sciences (KNAW)     

Psychisch Kranke: Gesehen aus zwei verschiedenen Perspektiven Ein methodischer Beitrag zur Einstellungsforschung in der Psychiatrie

Zusammenfassung Anhand von Daten aus zwei Bevölkerungsumfragen zur Einstellung gegenüber psychisch Kranken wird untersucht, welchen Einfluss die Variation der Perspektive-die des Befragten selbst versus die der anderen-auf das Befragungsergebnis hat. Wie erwartet fällt das Urteil über psychisch Kranke positiver aus, wenn nach der eigenen Meinung gefragt wird, als wenn man das Urteil der anderen einschätzen lässt. Der Unterschied zwischen beiden Frageformulierungen nimmt mit dem Grad der Schulbildung zu und erreicht bei Personen mit Abitur ein substantiell bedeutsames Ausmass. Darüber hinaus sind die Antworten eindeutiger und pointierter, wenn nach der persönlichen Meinung gefragt wird.

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Summary The impact of the change in perspective (i.e. the personal opinion of those questioned versus what they perceive the others' opinion toward the mentally ill to be) on the results of the questionnaire is examined based on data from two population surveys measuring attitudes towards the mentally ill. As expected, the respondents' attitudes towards the mentally ill are more positive if they are asked to give their own opinion. The impact that the variation of the two formulations of these questions has on the respondents increases with their level of education and reaches a substantial amount among those with Abitur. Furthermore, the answers are clearer and more definite if those questioned are asked for their personal opinion.

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Résumé L'impact d'un changement de perspective (opinion personnelle comparée à l'opinion générale telle qu'elle est personnellement perçue) est examiné dans le cadre de deux études de population mesurant l'attitude envers les malades psychiques. Comme on pouvait s'y attendre, l'attitude des répondants est beaucoup plus positive lorsqu'il s'agit de leur opinion personnelle. La divergence entre l'opinion personnelle et la perception de l'opinion générale augmente au fur et à mesure que le niveau d'éducation s'accroît. Les réponses sont d'autre part bien plus clairement formulées lorsque les personnes experiment leur opinion personnelle.

     

Mutagenicity of diisopropylamine dichloroacetate, the "active constituent" of vitamin B15 (pangamic acid)

Diisopropylamine dichloroacetate, the active component of many formulations of pangamic acid (trade-named "vitamin B15"), and diisopropylamine, a component of diisopropylamine dichloroacetate, both demonstrate mutagenicity in the Ames Salmonella/mammalian microsome mutagenicity test. Ninety percent of such agents prove carcinogenic, and this long-term possibility must be considered in any proposed use of pangamic acid containing diisopropylamine or diisopropylamine dichloroacetate.     

Comparison of pesticide and particulate recoveries with the vacuum and dislodgeable surface pesticide residue techniques

The dislodgeable and vacuum surface residue techniques were compared for the quantity of pesticide residue and quantity and quality of particulate matter removed from Valencia orange leaves. Data trends for dislodgeable and vacuum parathion and paraoxon residues were correlated at r0.95 for both emulsifiable concentrate and wettable powder formulations.The amount of pesticide residue and particulate matter obtained was dislodgeable > glass fiber filter > 5.0 filter > 0.8 filter. The flow rate of the filter was correlated with the amount of residue removed.The quality of particulate matter as judged by size analyses was equal The dislodgeable technique removed about five times more particulate material and about eleven times more pesticide residue compared to the vacuum technique.Florida Agricultural Experiment Stations Journal Series No. 745.     

Kahnbeinfrakturen – Diagnostik, Klassifikation und Therapie

Herbert's classification of scaphoid fractures provides the underlying rationale for treatment according to the fracture type. A CT bone scan in the long axis of the scaphoid is the best means of differentiating between stable and unstable fractures. This is difficult from conventional X-rays due to the particular three-dimensional anatomy of the scaphoid. To avoid long-term plaster immobilization and to diminish the risk of a nonunion, unstable fractures of type B should be fixed operatively. With headless screws such as the Herbert screw, which are now available in a cannulated shape, the majority of scaphoid fractures of type B1 and B2 can be stabilized using minimally invasive procedures. Severely displaced fractures require the classical open palmar approach. Proximal pole fractures (B3) are best managed from the dorsal approach, using the Mini-Herbert screw. Stable fractures of type A2 can be treated conservatively in a below-elbow cast or, alternatively, stabilized percutaneously, which allows early mobilization.