[The vision of interdisciplinary teams on an ambulatory nursing consultation]. / De visie van interdisciplinaire teams op een ambulant verpleegkundig spreekuur.

BACKGROUND: Several European countries are reforming their mental healthcare program. This implies an increase of pressure on outpatient care and also in Flanders are waiting times long in the outpatient care and patients don’t receive timely care. Hitherto, a nursing consultation in mental health care is a fairly new concept of care. AIM: To explore mental health care professionals’ point of view on outpatient nursing consultation in mental health care. METHOD: An explorative qualitative research with semi-structured interviews was conducted. Fifteen mental health care professionals from different wards were interviewed. A thematic analysis was used. RESULTS: Three main topics emerged: content, purpose and conditions for nursing consultation. The central topic of consultation should be patients’ quality of life when dealing with a mental illness and how support can be offered. The respondents found that the nurse functions as a mediator and provides continuity by playing an important role in observing and reporting. CONCLUSION: The research contributes to identifying the mental healthcare professionals’ view on nursing consultation in outpatient mental health care. The implementation of nursing consultation has to meet several conditions such as the nurse’s competences and training, interprofessional collaboration and organizational concerns e.g. financing and staffing.

[Autism spectrum disorder and schizophrenia: a challenging differential diagnosis]. / Autismespectrumstoornis en schizofrenie: een uitdagende differentiaaldiagnose.

Autism spectrum disorder and psychotic disorders/schizophrenia are separate disorders in the DSM-5. Due to overlapping symptoms and increased frequency in comorbidity they can be a diagnostic and therapeutic challenge in clinical practice. Relevant literature regarding the correlation between these disorders is discussed and linked to a case-report. An increased prevalence of autism/autistic traits is observed within psychotic patients and vice versa. Common symptoms and risk-factors, but also differential factors, are described. Despite of several hypotheses concerning increased frequency in comorbidity, no clear explanation was found so far. Little is known concerning treatment in case of comorbidity. In this case-report there was significant amelioration after treatment with an atypical antipsychotic. Psycho-education and attention to structuring are also important elements of the treatment plan.

[Depression and intermittent hypercortisolism: a difficult differential diagnostic process]. / Differentiaaldiagnose bij depressie en intermitterend hypercortisolisme.

Both Cushing’s and pseudo-Cushing’s syndrome involve a state of hypercortisolism. Cushing’s syndrome is a progressive multisystemic disease, caused by either the administration of corticosteroids, or the overproduction of cortisol by a tumoral process. In pseudo-Cushing’s syndrome the HPA-axis is hyperactive due to a pathophysiological process, most frequently caused by depression. The existence of a cyclic variant of Cushing’s syndrome, characterised by intermittent hypercortisolism, complicates the diagnosis in a patient with for example depression. In case of remaining intermittent hypercortisolism after remission of the depression, extreme hypercortisolism and (suspicion of) a tumor, we have to consider a cyclic Cushing syndrome. Also, in patients with treatment resistant depression or depression with atypical features combined with intermittent hypercortisolism psychiatrists have to consider a cyclic Cushing syndrome.

[Repetitive inappropriate sexual behaviour as a symptom of agitated depression: catatonic stereotypy?] / Repetitief onaangepast seksueel gedrag bij geagiteerde depressie: katatone stereotypie?

Catatonia is a psychomotor syndrome characterised by multiple symptoms like stereotypies - repetitive, abnormally frequent, non-goal-directed movements. A problem is the lack of unanimity regarding the number of symptoms needed for diagnosis. We describe repetitive inappropriate sexual behaviour in a patient with bipolar depression and excited catatonia with Bush-Francis Catatonia Rating Scale score of 12. Electroconvulsive therapy resulted in disappearance of catatonia and inappropriate sexual behaviour and remission of depression. A recurrent episode with similar inappropriate sexual behaviour was successfully treated with electroconvulsive therapy. We interpreted the repetitive inappropriate sexual behaviour as a catatonic stereotypy. Similar stereotypies are reported in children with autism. Tics and self-injury in patients with autism are described as a stereotypy within catatonia. The agitated depression is another possible diagnosis with the repetitive inappropriate sexual behaviour as an example of psychomotor agitation. More research is needed towards repetitive inappropriate sexual behaviour as a possible stereotypy within catatonia.

[Non-invasive neurostimulation in the treatment of child and adolescent psychiatry]. / Non-invasieve neurostimulatie als behandeling in de kinder- en jeugdpsychiatrie.

BACKGROUND: Neurostimulation is a potentially interesting treatment option for children and adolescents with psychiatric disorders.
AIM: To review the efficacy of two non-invasive neurostimulation techniques, namely repetitive transcranial magnetic stimulation (rtms) and transcranial direct current stimulation (tdcs), in the treatment of child and adolescent psychiatric disorders.
METHOD: We searched the literature research using PubMed.
RESULTS: There is some evidence that rtms is being used to treat unipolar depression, psychosis, autism spectrum disorder, attention deficit hyperactivity disorder and tic disorder. So far, however, very little research has been done on tdcs.
CONCLUSION: Further research is vitally important in order to ensure the safety and efficacy of rtms and tdcs.

[Rapid tranquillisation for agitated patients with psychostimulant intoxication]. / Acute ingrijpmedicatie bij de geagiteerde patiënt met intoxicatie met psychostimulantia.

BACKGROUND: Because psychostimulant intoxication can lead to serious health risks for the patient, it is often necessary to ensure that the patient receives both adequate medical surveillance and rapid tranquillisation.
AIM: To find out whether there is scientific evidence that psychopharmacological intervention helps patients with psychostimulant intoxication to manage aggression and agitation.
METHOD: We searched the literature systematically.
RESULTS: Our study showed that intravenous droperidol worked faster and was more effective than intravenous lorazepam in inducing sedation in patients intoxicated with psychostimulants. In other studies the number of patients intoxicated with psychostimulants was too small or the patient population was not described in sufficient detail for any meaningful conclusions to be drawn.
CONCLUSION: So far, research has been so limited that it has not yet provided convincing evidence about the best medication to use in the treatment of aggressive patients intoxicated with psychostimulants.

Therapeutic processes in multi-family groups for major depression: results of an interpretative phenomenological study.

BACKGROUND: Recent research indicates that different couple and family interventions are effective in the treatment of depressed patients. However, how these psychosocial interventions work, has been less well investigated. In order to better understand the underlying treatment processes, helpful treatment experiences of depressive patients and their partners were examined in a multi-family therapy group. METHOD: 24 patients hospitalized for depression and 20 partners participated in this study. Therapeutic factors were assessed using an open-ended questionnaire. Responses were analyzed using interpretative phenomenological approach (IPA). RESULTS: Eight recurring therapeutic factors were reported by both the patients and their partners: (1) Presence of others, (2) cohesion and understanding, (3) self-disclosure, (4) openness, (5) discussion, (6) insights, (7) observational experiences and (8) guidance from the therapist. LIMITATIONS: Results were not fed back to the participants following analysis and only therapeutic factors that operate on a conscious level could be identified. CONCLUSIONS: Several important therapeutic factors were identified in multi-family therapy groups for depression. These factors help to gain understanding into the processes, which should be emphasized in treatment and ought to be explored in future outcome and process research.

Coping with infertility: a body-mind group intervention programme for infertile couples.

BACKGROUND: The recognition of the distressing character of infertility diagnosis and treatment has led to the development of several psychosocial interventions for infertile couples. At the Leuven University Fertility Centre, a body-mind marital group intervention was developed to help infertile couples cope with the distress related to infertility. METHODS AND RESULTS: This treatment programme was originally adapted from a mind-body approach, but integrated concepts and techniques from body-oriented therapy, art therapy and multi-family group therapy. In this paper, the therapeutic foundations, treatment goals and practical implications of the mind-body marital group intervention are outlined. Further, the treatment procedure is explained in detail and illustrated by clinical vignettes. CONCLUSIONS: Although the first clinical impressions about the usefulness of the body-mind group programme in fertility clinics seem promising, further research is needed to assess its effectiveness.

An alpha-mercaptoacrylic acid derivative (PD150606) inhibits selective motor neuron death via inhibition of kainate-induced Ca2+ influx and not via calpain inhibition.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron death. The exact mechanism responsible for this selectivity is not clear, although it is known that motor neurons are very sensitive to excitotoxicity. This high sensitivity is due to a high density of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors on their surface and to a limited Ca(2+) buffering capacity. Ca(2+) can enter the cell upon stimulation through voltage-operated Ca(2+) channels and through the Ca(2+)-permeable portion of AMPA receptors. How this Ca(2+) kills motor neurons is incompletely understood. In the present study, we report that kainate (KA)-induced motor neuron death is purely mediated through Ca(2+) entering motor neurons through Ca(2+)-permeable AMPA receptors and that voltage-operated Ca(2+) channels play no significant role. In contrast to what has been observed in other neuronal models or after N-methyl-D-aspartate stimulation, NO synthase inhibition and a number of antioxidants did not protect motor neurons from KA-induced death. Only PD150606, derived from alpha-mercaptoacrylic acid and considered as a selective calpain antagonist, inhibited dose-dependently the KA-induced motor neuron death. However, other calmodulin and calpain inhibitors were not effective. At least part of the inhibitory effect of PD150606 is due to an irreversible inhibition of the Ca(2+) influx through the Ca(2+)-permeable AMPA receptor. These results demonstrate the interesting property of PD150606 to interfere with excitotoxicity-dependent motor neuron death and show that PD150606 is not an exclusive calpain/calmodulin antagonist.

Matrix metalloproteinase deficiencies do not impair cell-associated fibrinolytic activity.

The matrix metalloproteinase (MMP) and fibrinolytic (plasminogen/plasmin) systems cooperate in many (patho)physiological processes requiring extracellular proteolysis. The effect of MMP-3 (stromelysin-1), MMP-7 (matrilysin), MMP-9 (gelatinase B) or MMP-12 (metalloelastase) on cellular fibrinolytic activity was studied with the use of smooth muscle cells (SMC) and fibroblasts derived from mice with specific inactivation of these genes. Activation of cell-bound plasminogen by two-chain urokinase-type plasminogen activator (tcu-PA) was not significantly different with SMC or fibroblasts from the gene-deficient mice (78% to 140% of wild-type). For all cell types, very limited conversion of plasminogen to angiostatin-like kringle-containing fragments was observed (< 3% of the total cell-bound plasminogen). Activation of plasminogen in solution by cell-associated tcu-PA was also comparable for SMC or fibroblasts of the different genotypes (54% to 160% of wild-type). In vitro SMC migration on scrape wounded collagen-coated surfaces was comparable for wild-type, MMP-7(-/-), MMP-9(-/-) and MMP-12(-/-) SMC, but was significantly reduced for MMP-3(-/-) SMC (P < .005 vs. wild-type). Serum-free conditioned medium of MMP-3(-/-) and MMP-7(-/-) SMC or fibroblasts induced similar lysis of fibrin films as wild-type cells. These findings indicate that several interactions that have been described between these MMPs and the plasminogen/plasmin system in a purified system do not significantly affect plasmin-mediated cellular fibrinolytic activity under cell culture conditions.

Modulation of cell-associated plasminogen activation by stromelysin-1 (MMP-3).

Stromelysin-1 (MMP-3) cleaves a 55 kDa kringle 1-4 fragment, containing the lysine-binding site(s) involved in cellular binding, from 92 kDa plasminogen and removes a 17 kDa NH2-terminal fragment, containing the cellular receptor-binding site, from 45 kDa urokinase (u-PA), but a potential role of MMP-3 in the regulation of cellular fibrinolytic activity by affecting binding and/or activation of plasminogen and/or single-chain u-PA has not been established. Human plasminogen (input concentration 100 nM for 4x10(6) cells per ml) was shown to bind specifically to human monocytoid THP-1 cells, to murine MMP-3 deficient smooth muscle cells (SMC) and fibroblasts (1.9, 0.92 and 1.0x10(6) molecules per cell, respectively). Treatment with MMP-3 (final concentration 0-50 nM) of cells saturated with bound plasminogen (about 25 nM), overnight at 37 degrees C, resulted in a dose-dependent reduction of the amount of u-PA activatable plasminogen (reduction to 25-40% of the value in the absence of MMP-3). Immunoblotting with specific monoclonal antibodies and autoradiography of eluates of the cells treated with MMP-3 revealed cleavage of plasminogen into the 55 kDa fragment and miniplasminogen (kringle 5 plus the proteinase domain). Binding of human single chain u-PA (scu-PA) to human THP-1 and HT 1080 cells amounted to 2.5x10(6) and 7.1x10(6) molecules per cell, respectively. Treatment with MMP-3 (final concentration 0-25 nM) of cell-bound u-PA (about 17 nM for THP-1 and 47 nM for HT1080 cells), overnight at 37 degrees C, did not alter cell-associated u-PA activity, measured in a direct chromogenic substrate assay or in a plasminogen-coupled chromogenic substrate assay (residual u-PA activity always > or =85% of that without MMP-3 treatment). Autoradiography of 125I-labeled u-PA moieties, removed from the cells by treatment with acid or with phosphatidylinositol phospholipase C, confirmed that u-PA remained essentially intact after MMP-3 treatment. These data indicate that MMP-3 may downregulate cell-associated plasmin activity by decreasing the amount of activatible plasminogen, without affecting cell-bound u-PA activity.

Functional magnetic resonance imaging neuroactivation studies in normal subjects and subjects with the narcoleptic syndrome. Actions of modafinil.

Functional magnetic resonance imaging (fMRI) can be used to detect regional brain responses to changes in sensory stimuli. We have used fMRI to determine the amount of visual and auditory cortical activation in 12 normal subjects and 12 subjects with the narcoleptic syndrome, using a multiplexed visual and auditory stimulation paradigm. In both normal and narcoleptic subjects, mean cortical activation levels during the presentation of periodic visual and auditory stimulation showed no appreciable differences with either age or sex. Normal subjects showed higher levels of visual activation at 10:00 hours than 15:00 hours, with a reverse pattern in narcoleptic subjects (P = 0.007). The group differences in spatial extent of cortical activation between control and narcoleptic subjects were small and statistically insignificant. The alerting action, and imaging response, to a single oral dose of the sleep-preventing drug modafinil 400 mg were then determined and compared with placebo in both the 12 normal (8 given modafinil, 4 placebo) and 12 narcoleptic subjects (8 modafinil, 4 placebo). Modafinil caused an increase in self-reported levels of alertness in 7 of 8 narcoleptic subjects, but there was no significant difference between mean pretreatment and post-treatment activation levels as determined by fMRI for either normal or narcoleptic syndrome subjects given modafinil. However, in the modafinil-treated group of 8 normal and 8 narcoleptic subjects, there was a clock time independent correlation between the initial level of activation as determined by the pretreatment scan and the post-treatment change in activation (visual, P = 0.002; and auditory, P = 0.001). No correlation was observed in placebo-treated subjects (P = 0.99 and 0.77, respectively). Although limited by the small number of subjects, and the lack of an objective measure of alertness, the findings of this study suggest that low cortical activation levels in both normal and narcoleptic subjects are increased following the administration of modafinil. Functional magnetic resonance imaging may be a valuable addition to established studies of attention.

Regulation of gelatinase activity in mice with targeted inactivation of components of the plasminogen/plasmin system.

To investigate a potential physiological role of the plasminogen/plasmin system in activation of the matrix metalloproteinase (MMP) system, the distribution of latent and active MMP-2 (gelatinase A) or MMP-9 (gelatinase B) was monitored in aorta extracts and in serum-free conditioned cell culture medium obtained from wild-type (WT) mice and from mice with deficiency of tissue-type plasminogen activator (t-PA(-/-)), urokinase-type plasminogen activator (u-PA(-/-)), plasminogen activator inhibitor-1 (PAI-1(-/-)) or plasminogen (Plg(-/-)). In aorta extracts, the contribution of active MMP-2 to the total MMP-2 level ranged between 7 and 16% for the different genotypes, whereas active MMP-9 was not detected. The contribution of active 58 kDa MMP-2 to the total MMP-2 level (active plus latent) ranged between 14 and 29% (mean of 3 experiments) for fibroblasts of the different genotypes, and between 18 and 32% for smooth muscle cells, and was relatively constant in time (7-72 h). The contribution of active 83 kDa MMP-9 to the total MMP-9 level ranged between 15 and 29% for fibroblasts of the different genotypes and was relatively constant in time (24-72 h); corresponding values were 17 to 57% for smooth muscle cells, with the exception of Plg(-/-) smooth muscle cells which had undetectable levels of active MMP-9. Addition of plasmin(ogen) to the cell culture medium of fibroblasts did not significantly affect the distribution of active and latent MMP-2, but resulted in an approximately two-fold enhancement of the contribution of active MMP-9. In macrophages of Plg(-/-) mice, active MMP-9 was detected only when the cells were cultured in the presence of plasminogen. These data indicate that activation of proMMP-2 occurs independently of the physiological plasminogen activators and of plasmin(ogen) in all the cell types evaluated. Activation of proMMP-9 was enhanced in the presence of plasmin(ogen), but active MMP-9 was also detected in fibroblasts of Plg(-/-) mice, indicating that in vivo activation may occur via plasmin(ogen)-independent mechanisms.

Proton spectroscopy in the narcoleptic syndrome. Is there evidence of a brainstem lesion?

There is controversy regarding the relationship of structural or biochemical brainstem lesions to "idiopathic" narcolepsy. Most cases of the narcoleptic syndrome are considered to be idiopathic because no structural lesion is detectable, although some cases of secondary narcolepsy are known to be associated with no structural brainstem lesions. Using proton spectroscopy, we determined levels of ventral pontine metabolite pools in 12 normal subjects and 12 subjects with idiopathic narcolepsy. REM sleep is generated in ventral pontine areas. Proton spectroscopy was used to study levels of N-acetyl aspartate (NAA) as a marker of cell mass, creatine and phosphocreatine (Cr + PCr), and choline (Cho). The intensity of the peaks, as determined by the area under the peak (AUP), was measured. The AUP correlates with the quantity of chemical present. In this study, the ratios of NAA to Cr + PCr were similar in normal subjects and in narcoleptic subjects with idiopathic narcolepsy. No differences in measured metabolic ratio were observed in subjects who slept during the scan procedure compared with those who remained awake. Subjects with "symptomatic" narcolepsy accompanied by an obvious structural brain lesion were not studied. Proton spectroscopy of the brain initiates a new kind of neurochemistry, allowing the noninvasive study of metabolic pools in the living human brain without the use of any kind of tracer or radioactive molecule. In this study, there was no evidence of cell loss in the ventral pontine areas of subjects with the narcoleptic syndrome.

Changes in putamen N-acetylaspartate and choline ratios in untreated and levodopa-treated Parkinson's disease: a proton magnetic resonance spectroscopy study.

We have carried out single-voxel proton magnetic resonance spectroscopy centered on the putamen both ipsilateral and contralateral to the worst affected side in nine subjects with drug naive idiopathic Parkinson's disease (IPD); seven chronically levodopa-treated dyskinetic IPD subjects; and 11 age-matched healthy controls. Measurements of N-acetylaspartate (NAA)/choline (Cho), NAA/(Creatine + Phosphocreatine) (Cr + PCr), and Cho/(Cr + PCr) were made. We found a significant reduction in NAA/Cho ratios from the putamen contralateral to the most affected side in the drugnaive group (p = 0.009), but not the levodopa-treated IPD groups compared with controls. There were no significant differences in NAA/(Cr + PCr) or Cho/(Cr + PCr) ratios. In untreated IPD, reduced putaminal NAA/Cho ratios may reflect loss of nigrostriatal dopamine terminals or alternatively indicate a functional abnormality of striatal putaminal neurons, such as membrane dysfunction due to striatal deafferentation. This study suggests that NAA/Cho ratios may be affected by L-dopa therapy and this may provide a reversible marker of neuronal dysfunction in the striatum.

Use of apomorphine in parkinsonian patients with neuropsychiatric complications to oral treatment.

Neuropsychiatric side effects often complicate anti-Parkinsonian therapy and pose a significant problem in the optimal management of idiopathic Parkinson's disease. Several publications report a relative lack of neuropsychiatric side effects in Parkinsonian patients treated with subcutaneous apomorphine. To investigate this further, we have used subcutaneous apomorphine to treat 12 non-demented IPD patients with previous oral drug-related neuropsychiatric problems. Treatment with apomorphine allowed alteration of anti-Parkinsonian medication and led to the abolition or reduction of neuropsychiatric complications in all patients. The mechanism remains unclear but may be due, in part, to a reduction in oral medication or a psychotropic action of apomorphine, possibly due to the piperidine moiety in its structure, or both.

Functional magnetic resonance imaging of the acute effect of intravenous heroin administration on visual activation in long-term heroin addicts: results from a feasibility study.

This preliminary report is the first demonstration of the acute effects of diacetylmorphine (heroin) administration on functional activation in the human brain using functional magnetic resonance imaging (fMRI). Four opiate addicts who received regular prescriptions for heroin, underwent fMRI using a visual activation paradigm before and after a dose of 30 mg heroin. All four showed a decrease after the heroin dose in the extent of significant activation. This method shows promise for sequential scanning to determine brain activity in response to different drugs and routes of drug administration.

Proton magnetic resonance spectroscopy of the striatum in Parkinson's disease patients with motor response fluctuations.

We have performed proton magnetic resonance spectroscopy centred on the putamen contralateral to the worst affected side in 10 patients with idiopathic Parkinson's disease (PD) and motor response fluctuations and seven age matched healthy controls. In PD, there was striking reduction in the N-acetylaspartate (NAA) and creatine and NAA/choline ratios compared to controls. This pilot study provides in vivo evidence of striatal neuronal dysfunction in PD and further studies are in progress to establish if the observed changes are due to the disease process itself or due to chronic levodopa therapy.

Melatonin and insomnia.

The hypnotic action of melatonin 5 mg p.o. was explored in 15 subjects with psychophysiological insomnia in a double-blind controlled self-report questionnaire study. Melatonin or placebo was taken at 20.00 hours for a 1-week period in random order. Effects on sleep and wakefulness were monitored by visual analogue scale and structured interview. Bedtime, sleep onset time, estimated total sleep and wake time, as well as self-rated sleep quality, were not altered by melatonin, and estimates of next-day function did not change. The period of melatonin, treatment was retrospectively correctly identified by 8 of 15 subjects. Despite unchanged ratings of night sleep quality on the last night of each treatment, 7 of 15 subjects reported that sleep had subjectively improved to a minor extent in the week of active treatment. Side-effects attributed to melatonin included headache and an odd taste in the mouth. These data indicate that melatonin is probably of no clinical value in the management of psychophysiological insomnia.