[Treatment of post-traumatic stress disorder in people with intellectual disability]. / Behandeling van posttraumatische stressstoornis bij mensen met een laag IQ.

BACKGROUND: Patients with borderline intellectual functioning (BIF) or intellectual disability (ID) are more likely to develop post-traumatic stress disorder (PTSD). However, co-occurrence of BIF/ID and PTSD symptoms often leads to exclusion for treatment in regular mental health care centers.
AIM: To determine whether standard treatment programs for PTSD can be used in the treatment of patients with BIF/ID.
METHOD: Qualitative review of good practices, scientific literature and recent reports about BIF, ID and PTSD.
RESULTS: Literature on evidence-based treatment programs for PTSD suggests that there is no need to be reluctant in starting treatment in patients with BIF/ID. Adjustment of communication and tempo is recommended.
CONCLUSION: There is reason to believe that standard treatment can be used in treating patients with a low IQ. More research to confirm this assumption is necessary, taken into account the size of this patient group.

[The associations between God representations and suicidality among Christian patients with a major depressive disorder]. / De relatie tussen godsrepresentaties en suïcidaliteit bij christelijke patiënten met een depressieve stoornis.

BACKGROUND: Depression strongly increases the risk of suicide. Religion is described as a protective factor against suicide. Considering the emotional blunting associated with depression, it is important to investigate the affective dimension of religion. This dimension is conveyed in God representations.
AIM: To describe what types of God representation occur among Christian patients with major depressive disorder and to determine whether there is a relationship between types of God representation and suicide.
METHOD: Clinical and outpatients with a major depressive disorder (n=155) completed the Questionnaire God Representations and the Paykel Suicide Items. A k-means cluster analysis is applied to examine which types of God representations occur among depressed patients. Whether there is a relationship between the different God representations and suicide is examined by applying a linear regression analysis.
RESULTS: Depressed patients uphold two types of God representation: a positive type (n=82) with positive feelings towards God and where God was experienced as supportive, and a negative type (n=73) with anger and anxiety towards God and where God was experienced as passive. Patients with a negative type of God representation scored significantly higher on suicidality. The severity of depression was the main predictor of suicidality, but God representations were also related with a 4% increase in the explained variance.
CONCLUSION: In Christian patients with major depressive disorder a negative and a positive God representation emerged. Patients with a negative God representation mainly seem to feel abandoned by God. The suicidality is significantly increased in patients with a negative God representation, however, the increase in the proportion of the explained variance is small.

Essential diseases in prescribing: A national Delphi study towards a core curriculum in pharmacotherapy education.

AIMS: Prescribing is a core skill for junior doctors, yet 8-10% of their prescriptions contain errors. To ensure adequate training in prescribing, it is important to define the diseases for which junior doctors should be competent to prescribe. The aim of the present study was therefore to identify the essential diseases in prescribing for junior doctors. METHODS: A two-round Delphi consensus study was conducted among medical specialists, general practitioners, junior doctors, pharmacists and pharmacotherapy teachers from all eight academic hospitals in the Netherlands. Using a five-point Likert scale, the participants indicated for each item on an initial questionnaire whether it should be considered an essential disease for junior doctors. The items for which ≥80% of all respondents agreed or strongly agreed were accepted as essential diseases. RESULTS: Sixty-two participants completed the Delphi survey. In total, 63 of 220 items were considered to be essential diseases. CONCLUSION: This is the first Delphi consensus study identifying exact conditions that junior doctors must be able to prescribe for. The essential diseases can be used for training in prescribing and assessment of junior doctors' prescribing competence.

Olcegepant blocks neurogenic and non-neurogenic CGRPergic vasodepressor responses and facilitates noradrenergic vasopressor responses in pithed rats.

BACKGROUND AND PURPOSE: Olcegepant (BIBN4096BS) is a selective non-peptide CGRP receptor antagonist with acute antimigraine properties. Since systemic vascular tone is modulated by perivascular (primary sensory CGRPergic and sympathetic) nerves, this randomized study investigated in pithed rats the effect of acute i.v. treatment with olcegepant on the neurogenic and non-neurogenic: (i) CGRPergic vasodepressor responses; and (ii) noradrenergic vasopressor responses. The pithed rat is an experimental model predictive of systemic (cardio) vascular side effects. EXPERIMENTAL APPROACH: Seventy-five male Wistar rats (divided into 15 groups, n = 5 each) were pithed, artificially ventilated and prepared for: (i) spinal stimulation (T9 -T12 ; 0.56-5.6 Hz) of the sensory CGRPergic vasodepressor outflow or i.v. bolus injections (0.1-1 µg·kg-1 ) of α-CGRP, substance P or acetylcholine, which induced frequency-dependent or dose-dependent vasodepressor responses; or (ii) spinal stimulation (T7 -T9 ; 0.03-3 Hz) of the sympathetic vasopressor outflow or i.v. bolus injections (0.03-3 µg·kg-1 ) of noradrenaline, which produced frequency-dependent or dose-dependent vasopressor responses. KEY RESULTS: Olcegepant (1000 and 3000 µg·kg-1 , i.v.) dose-dependently blocked the vasodepressor responses to sensory nerve stimulation or i.v. α-CGRP, without affecting those to substance P or acetylcholine. Whereas it potentiated the vasopressor responses to sympathetic nerve stimulation or i.v. noradrenaline. CONCLUSIONS AND IMPLICATIONS: Olcegepant (i.v.) selectively blocked the neurogenic and non-neurogenic CGRPergic vasodepressor responses. This blockade by olcegepant potentiated the neurogenic and non-neurogenic noradrenergic vasopressor responses in pithed rats, an effect that might result in an increased vascular resistance and, consequently, in a prohypertensive action.

Field-free magnetization reversal by spin-Hall effect and exchange bias.

As the first magnetic random access memories are finding their way onto the market, an important issue remains to be solved: the current density required to write magnetic bits becomes prohibitively high as bit dimensions are reduced. Recently, spin-orbit torques and the spin-Hall effect in particular have attracted significant interest, as they enable magnetization reversal without high current densities running through the tunnel barrier. For perpendicularly magnetized layers, however, the technological implementation of the spin-Hall effect is hampered by the necessity of an in-plane magnetic field for deterministic switching. Here we interface a thin ferromagnetic layer with an anti-ferromagnetic material. An in-plane exchange bias is created and shown to enable field-free S HE-driven magnetization reversal of a perpendicularly magnetized Pt/Co/IrMn structure. Aside from the potential technological implications, our experiment provides additional insight into the local spin structure at the ferromagnetic/anti-ferromagnetic interface.

Hyperbaric oxygen for the treatment of diabetic foot ulcers: a systematic review.

OBJECTIVE: A systematic review of randomized clinical trials (RCTs) to assess the additional value of hyperbaric oxygen therapy (HBOT) in promoting the healing of diabetic foot ulcers and preventing amputations was performed. METHODS: MEDLINE, Embase, and the Cochrane Library were searched to identify RCTs in patients with diabetic foot ulcers published up to August 2013. Eligible studies reported the effectiveness of adjunctive HBOT with regard to wound healing, amputations, and additional interventions. RESULTS: Seven of the 669 identified articles met the inclusion criteria, comprising 376 patients. Three trials included 182 patients with ischaemic ulcers, two trials studied 64 patients with non-ischaemic ulcers, and two trials comprising 130 patients did not specify ulcer type. Two trials were of good methodological quality. Pooling of data was deemed inappropriate because of heterogeneity. Two RCTs in patients with ischaemic ulcers found increased rates of complete healing at 1-year follow-up (number needed to treat (NNT) 1.8 (95% CI: 1.1 to 4.6) and 4.1 (95% CI: 2.3 to 19)), but found no difference in amputation rates. A third trial in ischaemic ulcers found significantly lower major amputation rates in patients with HBOT (NNT 4.2, 95% CI: 2.4 to 17), but did not report on wound healing. None of the RCTs in non-ischaemic ulcers reported differences in wound healing or amputation rates. Two trials with unknown ulcer types reported beneficial effects on amputation rates, although the largest trial used a different definition for both outcomes. HBOT did not influence the need for additional interventions. CONCLUSION: Current evidence shows some evidence of the effectiveness of HBOT in improving the healing of diabetic leg ulcers in patients with concomitant ischaemia. Larger trials of higher quality are needed before implementation of HBOT in routine clinical practice in patients with diabetic foot ulcers can be justified.

Endosomal proteolysis regulates calcitonin gene-related peptide responses in mesenteric arteries.

BACKGROUND AND PURPOSE: Calcitonin gene-related peptide (CGRP) is a potent vasodilator, implicated in the pathogenesis of migraine. CGRP activates a receptor complex comprising, calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). In vitro studies indicate recycling of CLR●RAMP1 is regulated by degradation of CGRP in early endosomes by endothelin-converting enzyme-1 (ECE-1). However, it is not known if ECE-1 regulates the resensitization of CGRP-induced responses in functional arterial tissue. EXPERIMENTAL APPROACH: CLR, ECE-1a-d and RAMP1 expression in rat mesenteric artery smooth muscle cells (RMA-SMCs) and mesenteric arteries was analysed by RT-PCR and by immunofluorescence and confocal microscopy. CGRP-induced signalling in cells was examined by measuring cAMP production and ERK activation. CGRP-induced relaxation of arteries was measured by isometric wire myography. ECE-1 was inhibited using the specific inhibitor, SM-19712. KEY RESULTS: RMA-SMCs and arteries contained mRNA for CLR, ECE-1a-d and RAMP1. ECE-1 was present in early endosomes of RMA-SMCs and in the smooth muscle layer of arteries. CGRP induced endothelium-independent relaxation of arteries. ECE-1 inhibition had no effect on initial CGRP-induced responses but reduced cAMP generation in RMA-SMCs and vasodilation in mesenteric arteries responses to subsequent CGRP challenges. CONCLUSIONS AND IMPLICATIONS: ECE-1 regulated the resensitization of responses to CGRP in RMA-SMCs and mesenteric arteries. CGRP-induced relaxation did not involve endothelium-derived pathways. This is the first report of ECE-1 regulating CGRP responses in SMCs and arteries. ECE-1 inhibitors may attenuate an important vasodilatory pathway, implicated in primary headaches and may represent a new therapeutic approach for the treatment of migraine.

Electric-field control of domain wall motion in perpendicularly magnetized materials.

Domain wall motion in materials exhibiting perpendicular magnetic anisotropy has been the subject of intensive research because of its large potential for future spintronic devices. Recently, it has been shown that perpendicular anisotropy of thin films can be influenced by electric fields. Voltage-controlled magnetic switching has already been realized, which is envisioned to lead to low-power logic and memory devices. Here we demonstrate a radically new application of this effect, namely control of domain wall motion by electric fields. We show that an applied voltage perpendicular to a Co or CoB wire can significantly increase or decrease domain wall velocities. Velocity modification over an order of magnitude is demonstrated (from 0.4 to 4 µm s(-1)), providing a first step towards electrical control of domain wall devices. This opens up possibilities of real-time and local control of domain wall motion by electric fields at extremely low power cost.

Intravital microscopy on a closed cranial window in mice: a model to study trigeminovascular mechanisms involved in migraine.

The purpose of the study was to develop a mouse model to study trigeminovascular mechanisms using intravital microscopy on a closed cranial window. In addition, we studied exogenous and endogenous calcitonin gene-related peptide (CGRP)-mediated vasodilation in dural arteries. Arteries in C57BL/6Jico mice were constricted with endothelin-1, which reduced the baseline diameter by 65-75%. Subsequently, vasodilation was induced by alpha-CGRP, capsaicin or transcranial electrical stimulation of perivascular trigeminal nerves in the absence or presence of different concentrations of BIBN4096BS or sumatriptan. Both alpha-CGRP and capsaicin induced vasodilation in preconstricted arteries. Transcranial electrical stimulation also induced current-dependent relaxation of dural arteries with 100 microA producing maximal dilation in the control group. BIBN4096BS blocked the responses evoked by alpha-CGRP and capsaicin, as well as electrical stimulation, whereas sumatriptan attenuated only vasodilation induced by electrical stimulation. This model is likely to prove useful in dissecting elements of the trigeminovascular system and for exploring pathophysiological aspects of migraine, especially in future studies using transgenic mice with mutations relevant to those observed in patients with migraine.

Successful management of postinfarction ventricular septal rupture.

Ventricular septal rupture is a rare but devastating complication of acute myocardial infarction. Especially in patients with cardiogenic shock, right ventricular dysfunction or an inferior infarct mortality is very high. We present a case in which an 83-year-old patient survived rupture of the ventricular septum complicating an inferior myocardial infarction. Unlike most patients his haemodynamic status did not deteriorate and delayed elective surgical repair was carried out successfully.

Reduced complement activation during cardiopulmonary bypass does not affect the postoperative acute phase response.

OBJECTIVE: In the present study the relationship was evaluated between perioperative inflammation and the postoperative acute phase response in patients undergoing elective coronary artery bypass grafting (CABG) assisted by cardiopulmonary bypass (CPB). CPB circuits contained either non-coated- (UMS), Carmeda- (BPS) or Trillium-coated oxygenators (BAS). METHODS: Prospectively, 71 CABG patients were randomly allocated to one of the oxygenator groups (UMS: n=25, BPS: n=25 and BAS: n=21). Terminal complement complexes (TCC) and elastase were determined in plasma samples collected before, during and after bypass. Secretory phospholipase A2 (sPLA2) and C-reactive protein (CRP) were determined before and after bypass. RESULTS: Demographic, CPB and clinical outcome data were similar for the three groups. TCC and elastase increased during CPB, and decreased thereafter. Significant differences between the groups were present in the levels of TCC at the end of CPB (P=0.002) and at the first (P=0.012) and second (P<0.001) postoperative days, the BPS and BAS groups having reduced levels of TCC compared to the UMS group. Also elastase concentrations differed significantly between the groups at the end of CPB (P<0.001). The postoperative sPLA2 and CRP levels increased in all three groups on the first and second postoperative days, but no significant differences were present between the groups. CONCLUSIONS: Material-induced reduction of the inflammatory response during CPB does not affect the postoperative acute phase response. Thus, in CABG patients this response seems relatively unaffected by the composition and/or biocompatibility of the modern CPB circuit and rather to be evoked by surgical trauma, anesthetics and organ perfusion.

Alternative surgical exposure of the rat heart in vivo using a simple abdominal approach.

Access to the heart in laboratory rats is usually performed via a median sternotomy or a lateral thoracotomy. An alternative, less traumatic approach to the in vivo rat heart with improved survival is described. The technique uses an upper median laparotomy extending alongside the xyphoid bone. The xyphoid bone is retracted in a rostral direction, and a T-shaped cut is made in the diaphragm thus opening the thoracic cavity. Using a retractor the opening in the diaphragm is spread and the heart is exposed. We performed this abdominal approach in 23 anaesthetised and mechanically ventilated (for 2 h) rats and found physiologic intra-operative haemodynamics, a good postoperative recovery and 0% mortality.

Bovine isolated middle cerebral artery contractions to antimigraine drugs.

Ergot alkaloids, sumatriptan and the newer 5-HT1B/1D receptor agonists all contract cranial blood vessels and this effect seems to be primarily responsible for their efficacy in migraine. We have compared the contractile effects of a number of ergot and triptan derivatives on the bovine isolated middle cerebral artery and characterised the 5-hydroxytryptamine (5-HT) receptors involved by using 5-HT2A (ketanserin: 10, 30, 100 nM) and 5-HT1B/1D (GR127935: 30, 100, 300 nM) receptor antagonists. The rank order of agonist potency (pD2) was ergotamine (8.0+/-0.1) approximately dihydroergotamine (8.0+/-0.1) > avitriptan (7.4+/-0.3) >5-HT (7.0+/-0.1) > naratriptan (6.8+/-0.1) > methylergometrine (major metabolite of methysergide; 6.5+/-0.2) > rizatriptan (6.3+/-0.3) approximately zolmitriptan (6.2+/-0.1) approximately sumatriptan (6.0+/-0.2) approximately methysergide (5.9+/-0.3). The rank order of efficacy (Emax expressed as % of contraction to 100 mM K+) was 5-HT (127+/-11) > sumatriptan (56+/-5) > ergotamine (48+/-5) approximately dihydroergotamine (44+/-8) approximately methyl-ergometrine (44+/-7) > avitriptan (37+/-7) approximately rizatriptan (33+/-5) approximately methysergide (29+/-10) approximately zolmitriptan (28+/-3) approximately naratriptan (23+/-2). The concentration-response curve to 5-HT appeared to be biphasic in the presence of 100 nM ketanserin, which hardly affected sumatriptan-induced contractions, but clearly antagonised the second more efficacious phase of the curve to 5-HT. On the other hand, GR127935 caused a rightward shift of the concentration-response curves to 5-HT (in the presence of 10 microM ketanserin) and sumatriptan with pA2 values of 7.0 and 8.1, respectively. In conclusion, all acutely acting antimigraine drugs contract the bovine isolated middle cerebral artery. Whereas sumatriptan contracts the artery via the 5-HT1B/1D receptor, the 5-HT-induced contraction is mediated partly by the 5-HT2A receptor and partly by another, possibly novel receptor differing from the 5-HT1B/1D receptor. This receptor may be a target for the development of future antimigraine drugs.

Influence of electrode site and size on variability of magnetic evoked potentials.

Successive magnetic evoked potentials (MEPs) concern varying motor neurons. We investigated whether this MEP-specific source of variability depends on electrode site and size. Amplitude variability (standard deviation) was largest over the center of the hypothenar muscles. Latencies were longer at distal and proximal sites than at the center site. Large electrodes (10 cm2) did not decrease this source of amplitude variability compared with EEG electrodes, in contrast to other sources of variability.

Angiotensin-converting enzyme in the human heart. Effect of the deletion/insertion polymorphism.

BACKGROUND: An insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with differences in the plasma levels of ACE as well as with myocardial infarction, cardiomyopathy, left ventricular hypertrophy, and coronary artery disease. METHODS AND RESULTS: We determined the cardiac ACE activity and the ACE genotype in 71 subjects who died of noncardiac disorders. Cardiac ACE activity was significantly higher (P < .01) in subjects with the ACE DD genotype (12.7 +/- 1.9 mU/g wet wt) compared with subjects with the ID (8.7 +/- 0.8 mU/g) and the II (9.1 +/- 1.0 mU/g) genotypes. This difference was independent of sex, age, and the time required for tissue collection. CONCLUSIONS: Cardiac ACE activity is highest in subjects with the DD genotype. Elevated cardiac ACE activity in these subjects may result in increased cardiac angiotensin II levels, and this may be a mechanism underlying the reported association between the ACE deletion polymorphism and the increased risk for several cardiovascular disorders.