Abnormal sensorimotor integration is related to disease severity in Parkinson's disease: a TMS study.

Hyperexcitability of the motor system has been reported in Parkinson's disease (PD). We evaluate how cutaneous afferents modulate motor excitability in PD patients and whether abnormal modulation is correlated to parkinsonian symptoms. Digital stimulation causes abnormal enhancement of motor responses in patients. This effect may be one of the features of motor hyperexcitability in PD. Cutaneomotor hyperexcitability correlates with clinical scores, suggesting that abnormal processing of cutaneous inputs might contribute to the pathogenesis of parkinsonian symptoms.     

Increased myocardial inositol trisphosphate levels during alpha 1-adrenergic stimulation and reperfusion of ischaemic rat heart.

Although stimulated [3H] inositol phosphate turnover has been demonstrated in isolated, perfused [3H] inositol prelabelled rat hearts, there is still no information regarding Ins (1,4,5)P3 levels in intact cardiac muscle. Using a D-myo-Ins(1,4,5)P3 assay system, Ins(1,4,5)P3 levels were determined in isolated perfused rats hearts during ischaemia, reperfusion and alpha 1-adrenergic stimulation via noradrenaline (3 x 10(-5) M). Control hearts contained +/- 674 pmols Ins(1,4,5)P3/g dry heart weight. Myocardial Ins(1,4,5)P3 levels were significantly decreased (+/- 389 pmols/g dry heart weight) after exposure to 20 mins of normothermic ischaemic cardiac arrest (NICA). Reperfusion produced a marked increase in Ins(1,4,5,)P3 levels (+/- 1,115 pmols/g dry heart weight) after only 30 s. Noradrenaline caused a 3-4 fold increase in tissue Ins(1,4,5)P3 levels within 30 s. After 20 mins stimulation with noradrenaline, the Ins(1,4,5)P3 levels were still significantly elevated. The rise in tissue Ins(1,4,5)P3 levels during reperfusion as well as during noradrenaline administration was counteracted by neomycin (0.5 x 10(-3) M), an inhibitor of phosphoinositidase specific phospholipase C. In both events neomycin restored the Ins(1,4,5)P3 levels to control values. For correlation of tissue Ins(1,4,5)P3 levels with mechanical events, noradrenaline (3 x 10(-5) M), in the presence of 10 mM LiCl, 10(-7) M propranolol and 10(-7) M atropine, was administered to isolated perfused rat hearts and the mechanical performance recorded over a period of 20 mins. Noradrenaline caused a significant increase in peak systolic pressure and work performance which was maintained for at least 10 mins, suggesting that the positive inotropic effects of noradrenaline may be provoked by Ins(1,4,5)P3. Furthermore, the finding that 20 min NICA followed by 30 s reperfusion causes an immediate significant increase in Ins(1,4,5)P3 content suggests a role for the phosphatidylinositol pathway in the intracellular Ca2+ overloading, characteristic of ischaemia-reperfusion.     

Fortlaufende Messung des Hämoglobinkonzentration des strömenden Blutes,insbesondere zur Bestimmung des Herzzeitvolumnes mit der Teststoffinjektionsmethode

Ohne Zusammenfassung     

Comparative study of nitroglycerin and molsidomine. Effects on the integrated systemic venous bed and the arterial pressure in dogs.

The effect of nitroglycerin, N-carboxy-3-morpholino-sydnonimine-ethylester (molsidomine, Corvaton), and its metabolite 3-morpholinosydnonimine upon the peripheral circulation was investigated in 38 dogs with cardio-pulmonary bypass. The three compounds increased the integrated systemic venous blood volume and decreased the mean arterial pressure. The time course of the action of nitroglycerin was different from that of molsidomine: The arterial and venous effects of nitroglycerin began immediately after the injection was started, reached a maximum, and had disappeared after 7 min. The effects of molsidomine started later and showed no tendency to decrease during the observation period of 30 min. When referred to the same decrease in arterial blood pressure, molsidomine acted more strongly upon the systemic venous bed than did nitroglycerin. The arterial and venous effects of the molsidomine metabolite could be antagonized by a dopamine infusion. It is concluded that the hypotensive effect of the three compounds observed in the intact circulation is due to the diminuation of peripheral resistance as well as to the dilatation of the systemic venous bed. The dilatation of the veins effects a decrease in the venous return and thereby in the cardiac output and the arterial pressure. It can be concluded that the antianginal effect of the three compounds is not only due to the diminution of the afterload of the heart; the diminution of the heart; the diminution of the preload also represents an important component of action.     

First Evaluation of a Population-Based Screen to Detect Emotional-Behavior Disorders in Orphaned Children in Sub-Saharan Africa

Due to the HIV/AIDS pandemic which has left 12 million children orphaned in Sub-Saharan Africa, children are at increased risk for mental health problems. Currently, no validity data exist for any screening measure of emotional-behavior disorders in pre-adolescent children in Sub-Saharan Africa. The aims of the current study were to evaluate the construct validity of the caregiver-, teacher-, and self-report versions of the one-page Strengths and Difficulties Questionnaire (SDQ) in 466 orphans in South Africa between the ages of 7 and 11 (M _age = 9.23 years, SD = 1.33, 51.93 % female) and to provide, for the first time, clinical cut-offs for this population. Findings demonstrated support for the caregiver SDQ, but not the teacher and self-report versions. We provide clinical cut-offs, but caution their use before further research is conducted. There remains a critical need for further psychometric studies of the SDQ in the developing world.     

Trichotillomania (hair pulling disorder), skin picking disorder,and stereotypic movement disorder: toward DSM‐V

In DSM‐IV‐TR, trichotillomania (TTM) is classified as an impulse control disorder (not classified elsewhere), skin picking lacks its own diagnostic category (but might be diagnosed as an impulse control disorder not otherwise specified), and stereotypic movement disorder is classified as a disorder usually first diagnosed in infancy, childhood, or adolescence. ICD‐10 classifies TTM as a habit and impulse disorder, and includes stereotyped movement disorders in a section on other behavioral and emotional disorders with onset usually occurring in childhood and adolescence. This article provides a focused review of nosological issues relevant to DSM‐V, given recent empirical findings. This review presents a number of options and preliminary recommendations to be considered for DSM‐V: (1) Although TTM fits optimally into a category of body‐focused repetitive behavioral disorders, in a nosology comprised of relatively few major categories it fits best within a category of motoric obsessive–compulsive spectrum disorders, (2) available evidence does not support continuing to include (current) diagnostic criteria B and C for TTM in DSM‐V, (3) the text for TTM should be updated to describe subtypes and forms of hair pulling, (4) there are persuasive reasons for referring to TTM as “hair pulling disorder (trichotillomania),” (5) diagnostic criteria for skin picking disorder should be included in DSM‐V or in DSM‐Vs Appendix of Criteria Sets Provided for Further Study, and (6) the diagnostic criteria for stereotypic movement disorder should be clarified and simplified, bringing them in line with those for hair pulling and skin picking disorder. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

A multiple-group measurement scale for interprofessional collaboration: Adaptation and validation into Italian and German languages

This article presents a study that aimed to validate a translation of a multiple-group measurement scale for interprofessional collaboration (IPC). We used survey data gathered over a three month period as part of a mixed methods study that explored the nature of IPC in Northern Italy. Following a translation from English into Italian and German the survey was distributed online to over 5,000 health professionals (dieticians, nurses, occupational therapists, physicians, physiotherapists, speech therapists and psychologists) based in one regional health trust. In total, 2,238 different health professions completed the survey. Based on the original scale, three principal components were extracted and confirmed as relevant factors for IPC (communication, accommodation and isolation). A confirmatory analysis (3-factor model) was applied to the data of physicians and nurses by language group. In conclusion, the validation of the German and Italian IPC scale has provided an instrument of acceptable reliability and validity for the assessment of IPC involving physicians and nurses.     

CREB Activation and Ischaemic Preconditioning

PURPOSE: Previous studies from our laboratory showed that activation of p38 MAPK is one of the triggers of ischaemic preconditioning. The signalling events downstream of p38 MAPK and their links to the putative final effectors of preconditioning are not clear. The cAMP responsive element-binding protein (CREB) is also phosphorylated by exposure to short episodes of ischaemia/reperfusion, suggesting a triggering action. The aim of this study was to systematically investigate (1) the signalling pathways leading to CREB phosphorylation during an ischaemic or beta-adrenergic preconditioning protocol (2) changes in CREB phosphorylation during sustained ischaemia and their significance in ischaemia/reperfusion injury. METHODS: The isolated perfused working rat heart was preconditioned by 1 x 5 min global ischaemia or 3 x 5 min global ischaemia and freeze-clamped. Drugs to manipulate CREB activation were added 5 min before onset of ischaemia. Non-preconditioned and preconditioned hearts were subjected to 25 min global or 35 min regional ischaemia, followed by 30 min reperfusion. Infarct sizes were determined using tetrazolium staining. Phosphorylation of CREB was determined by Western blots. RESULTS: Exposure of hearts to 5 min global ischaemia followed by reperfusion, significantly increased CREB phosphorylation This is mediated by, amongst others, release of endogenous catecholamines and adenosine, as indicated by the use of receptor blockers. Events downstream of receptor stimulation were evaluated using inhibitors for PKA (H89), MSK-1 (H89, Ro318220), PKC (bisindolylmaleimide), p38 MAPK (SB203580) and ERK (PD98059). Activation of PKA, PKC, ERK and p38 MAPK is involved in preconditioning-induced CREB phosphorylation. Ischaemia-induced activation of iPLA(2) and cPLA(2) also contribute to CREB phosphorylation as indicated by the use of the inhibitors 4-bromo-enol-lactone (BEL) and AACOF(3,) respectively. Inhibition of CREB phosphorylation by either BEL or AACOF(3) during a preconditioning protocol partially attenuated cardioprotection. CREB phosphorylation was attenuated during sustained global ischaemia of both non-preconditioned and preconditioned hearts. CONCLUSIONS: These data suggest that CREB phosphorylation during an ischaemic preconditioning protocol may contribute to triggering preconditioning, while reduced phosphorylation during sustained ischaemia does not appear to be associated with cardioprotection.     

Coronary collateral flow: effect of drugs and perfusion pressure

Summary In 35 mongrel dogs acute myocardial infarction was produced by ligating the anterior descending branch of the left coronary artery and subsequent embolization of the peripheral area of the descending branch with microspheres. Retrograde flow and coronary retrograde pressure were measured before and after embolization as well as after embolization before and during the action of coronary dilating drugs. After embolization, the mean retrograde flow represented the whole coronary collateral flow, and the retrograde pressure equalled the true coronary collateral perfusion pressure. Following embolization, the mean retrograde pressure significantly increased from 20±2 to 69±3 mm Hg, i.e. to 73% of the mean aortic pressure. There was a simultaneous rise in retrograde flow from 3.99±0.78 to 6.19±1.16 ml/(min · 100 g), i.e. 12% of the antegrade perfusion. A significant correlation between coronary collateral flow and collateral perfusion pressure could be demonstrated. The average increase in collateral flow was 1.14 ml/(min · 100 g), i.e. 21 %, when the perfusion pressure rose from 70 to 80 mm Hg.After drug infusions, a slight increase in coronary collateral flow was observed, provided that the perfusion pressure remained unchanged. This increase was significant after nitroglycerine (+ 13±3 %) and after papaverine (+ 11±5%). When the perfusion pressure decreased, there was a decrease in collateral flow. When, however, under isoproterenol the decreased perfusion pressure was brought back to control level my means of a blood infusion, the collateral flow also increased and was then slightly, but significantly, above control (+ 4%).It can be concluded that, provided the perfusion pressure remains constant, the application of coronary dilating drugs can slightly improve the coronary collateral flow. This small effect might be of vital importance for the treatment of myocardial infarction. Myocardial steal only appeared when the perfusion pressure decreased.

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Über den Einfluß von Pharmaka und des Perfusionsdruckes auf die Kollateraldurchblutung des Herzens

Zusammenfassung Bei 35 narkotisierten Hunden wurde der Ramus descendens der linken Koronararterie akut unterbunden und das zugehörige Stromgebiet mit Latexpartikeln embolisiert. Der retrograde Fluß und der retrograde Druck wurden vor und nach Embolisation sowie nach der Embolisation vor und während des Einflusses von Koronardilatatoren gemessen. Der retrograde Fluß nach Mikroembolisation entspricht dem wahren Kollateralfluß und der retrograde Druck dem wahren Perfusionsdruck der Kollateralgefäße. Nach Mikroembolisation stieg der retrograde Druck signifikant von 20±2 auf 69±3 mm Hg, das entspricht 73% des mittleren Aortendruckes. Gleichzeitig stieg der retrograde Fluß von 3,99±0,78 auf 6,19±1,16 ml/(min · 100 g), das sind 12% der antegraden Durchblutung. Der durchschnittliche Anstieg der Kollateraldurchblutung betrug 1,14 ml/(min. · 100 g), das sind + 21%, bei einer Zunahme des Perfusionsdruckes von 70 auf 80 mm Hg.Unter der Applikation von Koronardilatatoren konnte ein geringer Anstieg der Kollateraldurchblutung beobachtet werden, vorausgesetzt, daß der Perfusionsdruck unverändert blieb. Dieser Anstieg war unter Nitroglycerin, (+ 13 ±3%) und unter Papaverin (+11±5%) signifikant. Die Kollateraldurchblutung nahm ab, wenn der Perfusionsdruck unter dem Einfluß des Pharmakons abfiel. Wurde der unter Isoproterenol gesunkene Perfusionsdruck mittels Bluttransfusion wieder auf den Ausgangswert angehoben, so stieg die Kollateraldurchblutung wieder an und lag dann mit +4% gering, aber signifikant über dem Ausgangswert.Aufgrund dieser Befunde kann geschlossen werden, daß Koronardilatatoren die Kollateraldurchblutung geringgradig verbessern können unter der Voraussetzung, daß der Perfusionsdruck nicht absinkt. Dieser geringe pharmakologische Effekt könnte jedoch von entscheidender Bedeutung bei der Behandlung des Myokardinfarktes sein. Ein myocardial steal tritt nur bei einem Abfall des Perfusionsdruckes ein.

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With 2 figures and 3 tables

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Supported by a grant of the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 30, Kardiologie, Düsseldorf.