Review of international clinical guidelines for adolescents on transition to Adult Mental Health Services and adults with attention-deficit hyperactivity disorder and their application to an irish context.

OBJECTIVES: To review the available clinical guidelines from Canada, North America, Europe and the United Kingdom for the diagnosis and management of attention-deficit hyperactivity disorder (ADHD) for adolescents previously diagnosed in Child and Adolescent Mental Health Services (CAMHS) on transition to Adult Mental Health Services (AMHS) and for adults presenting with a diagnostic query re-ADHD. This article seeks to apply the available guidelines to an Irish context. METHOD: Various clinical guidelines and consensus statements were identified by a literature search of PubMed, incorporating literature from the past 10 years from English speaking countries and inclusion of any additional guidelines of clinical relevance. A clinical guideline with specific reference for Irish clinicians was proposed for the diagnosis and management of adults presenting for the first time with a diagnostic query re-ADHD and also to include those young adults previously diagnosed in CAMHS on transition to AMHS. CONCLUSIONS: ADHD is a lifelong disorder, which if undiagnosed or untreated can lead to significant impairment resulting in a high economic cost for society. Stimulant medication is a first-line treatment option for adults with ADHD; however, some formulations are unlicensed in Ireland. Recent licensing of Atomoxetine, for both adolescents on transition and for adults with newly diagnosed ADHD is a welcome development. Third-line agents are rarely prescribed due to their side effect profiles and are prescribed off-label: It is important to establish clinical guidelines for an Irish context incorporating a biopsychosocial approach. Further discussion amongst clinicians and stakeholders is needed to plan service development.

Review of clinical guidelines for children and adolescents with attention deficit hyperactivity disorder and their application to an Irish context.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with international prevalence rates estimated to be 5%. It is currently the most common disorder treated in Child and Adolescent Mental Health Services in Ireland. There have been a number of guidelines worldwide produced to aid clinicians in the diagnosis and treatment of ADHD; however, there are no guidelines available specifically for the Irish population and healthcare system. OBJECTIVES: The aim of this paper is to review the available clinical guidelines for the diagnosis and management of ADHD in children adolescents across North America, Canada, Europe and the United Kingdom and to apply these to an Irish context. METHODS: A number of international guidelines were reviewed. A proposed pathway for the assessment and treatment of children and adolescents with ADHD has been devised with the recommendation that a formalised consensus guideline should be implemented. CONCLUSION: This review paper has highlighted that there is consensus between the guidelines for the diagnosis of ADHD with a thorough clinical history remaining the gold standard. They further agree on the importance of identifying co-morbid disorders. When it comes to the treatment, the guidelines are less unified. This current paper has devised a proposed care pathway for ADHD in Ireland to ensure high quality cost effective care within its healthcare system.

Paediatric psychotropic prescribing practices in Ireland.

OBJECTIVES: This study describes the attitudes, knowledge and prescribing of psychotropic medication in children. METHOD: A study-specific questionnaire was mailed to all child psychiatrists, paediatricians and a group of registered general practitioners (GPs) from a selected Child and Adolescent Mental Health Services catchment area. RESULTS: In the 116 respondents who replied (39% response rate), psychotropic medication was generally valued and used by all groups (70.1%). Respondents believed that the majority (61.9%) of their non-medical colleagues would also value/support the use of medication and this endorsement influenced the respondents' prescribing rates. Initiating medication was viewed as the province of child psychiatry (78.6%). Medication is felt to be justified in a wide variety of mental health disorders, their use being reserved for severe presentations, with psychostimulants and selective serotonin reuptake inhibitors being most used. A significant number of GPs (60.9%) and paediatricians (63.4%) were felt to be lacking in competence in psychotropic prescribing, with a general request for more seminars in this area (61.5%) with almost half (45%) of them believing that they would prescribe more often. CONCLUSION: The use of psychotropic medication in children remains a valued and common practice in Ireland. Attitudinal and practice differences across professional groups exist, and although the experience is one of relative safety there was a strong desire for further education leading to a perceived increase in utilisation. The impact of perceived public opinion regarding psychotropic prescribing along with a lack of competence may represent a major barrier to effective prescribing, thus highlighting the importance of ongoing professional development and increased public health initiatives to increase knowledge and understanding in this increasingly important area.

Acceptance as a process variable in relation to catastrophizing in multidisciplinary pain treatment.

BACKGROUND: The underlying processes of change that contribute to the effectiveness of multidisciplinary pain treatment require clarification. Previous research has found support for pain acceptance as a process variable in acceptance-based treatment. Preliminary findings indicate that pain acceptance may also be a process variable in traditional cognitive behavioural therapy (CBT). The aim of this study was to investigate the role of pain acceptance as a process variable in CBT relative to two empirically supported process variables, namely catastrophizing and pain intensity. METHODS: Patients with chronic pain (n = 186) attended a 3-week, multidisciplinary pain programme, which was CBT based. Patients completed a measure of pain intensity; the Chronic Pain Acceptance Questionnaire; the catastrophizing subscale of the Pain Response Self-Statements Scale; the Roland Morris Disability Questionnaire; the Depression Anxiety and Stress Scale; and two measures of physical functioning at pretreatment, post-treatment and 3-month follow-up. RESULTS: Both acceptance and catastrophizing showed statistically significant and clinically relevant changes from pre- to post-treatment. Changes in both acceptance and catastrophizing showed a significant correlation with changes in almost all of the outcome variables. Regression analyses demonstrated that change in acceptance was a significant predictor of changes in depression, disability, timed walk and sit-to-stand performance, after controlling for changes in catastrophizing and pain intensity. CONCLUSIONS: Although not specifically targeted in CBT treatment, acceptance of pain was an important process variable that contributed to CBT treatment outcomes after controlling for changes in pain intensity and catastrophizing. Implications for future research and clinical practice are discussed.

Cuticle thickening associated with pyrethroid resistance in the major malaria vector Anopheles funestus.

BACKGROUND: Malaria in South Africa is primarily transmitted by Anopheles funestus Giles. Resistance to pyrethroid insecticides in An. funestus in northern Kwazulu/Natal, South Africa, and in neighbouring areas of southern Mozambique enabled populations of this species to increase their ranges into areas where pyrethroids were being exclusively used for malaria control. Pyrethroid resistance in southern African An. funestus is primarily conferred by monooxygenase enzyme metabolism. However, selection for this resistance mechanism is likely to have occurred in conjunction with other factors that improve production of the resistance phenotype. A strong candidate is cuticle thickening. This is because thicker cuticles lead to slower rates of insecticide absorption, which is likely to increase the efficiency of metabolic detoxification. RESULTS: Measures of mean cuticle thickness in laboratory samples of female An. funestus were obtained using scanning electron microscopy (SEM). These females were drawn from a laboratory colony carrying the pyrethroid resistance phenotype at a stable rate, but not fixed. Prior to cuticle thickness measurements, these samples were characterised as either more or less tolerant to permethrin exposure in one experiment, and either permethrin resistant or susceptible in another experiment. There was a significant and positive correlation between mean cuticle thickness and time to knock down during exposure to permethrin. Mean cuticle thickness was significantly greater in those samples characterised either as more tolerant or resistant to permethrin exposure compared to those characterised as either less tolerant or permethrin susceptible. Further, insecticide susceptible female An. funestus have thicker cuticles than their male counterparts. CONCLUSION: Pyrethroid tolerant or resistant An. funestus females are likely to have thicker cuticles than less tolerant or susceptible females, and females generally have thicker cuticles than males. In pyrethroid resistant An. funestus, this increase in cuticle thickness is likely to have developed as an auxiliary to the primary mode of pyrethroid resistance which is based on enzyme-mediated detoxification.

Redox-mediated substrate recognition by Sdp1 defines a new group of tyrosine phosphatases.

Reactive oxygen species trigger cellular responses by activation of stress-responsive mitogen-activated protein kinase (MAPK) signalling pathways. Reversal of MAPK activation requires the transcriptional induction of specialized cysteine-based phosphatases that mediate MAPK dephosphorylation. Paradoxically, oxidative stresses generally inactivate cysteine-based phosphatases by thiol modification and thus could lead to sustained or uncontrolled MAPK activation. Here we describe how the stress-inducible MAPK phosphatase, Sdp1, presents an unusual solution to this apparent paradox by acquiring enhanced catalytic activity under oxidative conditions. Structural and biochemical evidence reveals that Sdp1 employs an intramolecular disulphide bridge and an invariant histidine side chain to selectively recognize a tyrosine-phosphorylated MAPK substrate. Optimal activity critically requires the disulphide bridge, and thus, to the best of our knowledge, Sdp1 is the first example of a cysteine-dependent phosphatase that couples oxidative stress with substrate recognition. We show that Sdp1, and its paralogue Msg5, have similar properties and belong to a new group of phosphatases unique to yeast and fungal taxa.

An audit of orthodontic referrals using IOTN as a comparison.

UNLABELLED: It is important that resources for orthodontic treatment within the Health Service Executive (HSE) are directed towards those children most in need of treatment. At present, children are referred using existing HSE guidelines. OBJECTIVES: To assess the level of treatment need in a sample of patients on the orthodontic waiting list in the North Eastern division of the HSE using the Index of Orthodontic Treatment Need (IOTN) as an objective comparison. Also, to compare these results with the findings of a similar audit in 2003 and to assess the effectiveness of recommendations from the 2003 audit. METHOD: Fifty models from each of two orthodontic units were selected. These were scored for the dental health component (DHC) and aesthetic component (AC) of IOTN by a calibrated examiner. RESULTS: In the 2005 audit, 100% of patients fell into DHC grades 4 or 5. These grades constitute a great need for treatment on dental health grounds. In the 2003 audit, 97% of patients fell into these two grades. The remaining 3% of children in 2003 were fostered and therefore entitled to orthodontic treatment under HSE guidelines. An average of 63.5% of patients fell into AC grades 8-10, i.e., deemed to be in great need of treatment on aesthetic grounds. CONCLUSION: The HSE screening guidelines identify patients in great need of orthodontic treatment using IOTN as an objective assessment of this need. The sensitivity of these guidelines requires assessment by measuring the level of unmet treatment need in 15-year-olds in the region. Recommendations arising from the 2003 audit relating to the filling of referral forms and the improvement of study model quality were found to have been effective.

In vivo occupancy of female rat brain estrogen receptors by 17beta-estradiol and tamoxifen.

Estrogens or antiestrogens are currently used by millions of women, but the interaction of these hormonal agents with brain estrogen receptors (ER) in vivo has not been characterized to date. Our goal was to assess, in vivo, the extent and regional distribution of brain ER occupancy in rats chronically exposed to 17beta-estradiol (E(2)) or tamoxifen (TAM). For that purpose, female ovariectomized Sprague-Dawley rats were implanted with subcutaneous pellets containing either placebo (OVX), E(2), or TAM for 3 weeks. ER occupancy in grossly dissected regions was quantified with 16alpha-[(18)F]fluoroestradiol ([(18)F]FES). Both E(2) and TAM produced significant decreases in radioligand uptake in the brain although the effect of E(2) was larger and more widespread than the effect of TAM. Detailed regional analysis of the interaction was then undertaken using a radioiodinated ligand, 11beta-methoxy-16alpha-[(125)I]iodo-estradiol ([(125)I]MIE(2)), and quantitative ex vivo autoradiography. E(2) treatment resulted in near-complete (86.6 +/- 17.5%) inhibition of radioligand accumulation throughout the brain, while ER occupancy in the TAM group showed a marked regional distribution such that percentage inhibition ranged from 40.5 +/- 15.6 in the ventrolateral part of the ventromedial hypothalamic nucleus to 84.6 +/- 4.5 in the cortical amygdala. These results show that exposure to pharmacologically relevant levels of TAM produces a variable, region-specific pattern of brain ER occupancy, which may be influenced by the regional proportion of ER receptor subtypes. These findings may partially explain the highly variable and region-specific effects observed in neurochemical, metabolic, and functional studies of the effects of TAM in the brain of experimental animals as well as human subjects.

Facile sequencing of oligosaccharides by matrix-assisted laser desorption/ionisation on a hybrid quadrupole orthogonal acceleration time-of-flight mass spectrometer.

N-Linked oligosaccharide mixtures released from a number of standard glycoproteins were derivatised with 3-acetylamino-6-acetylaminoacridine (AA-Ac) using reductive amination. Analysis of these mixtures using an experimental matrix-assisted laser desorption/ionisation (MALDI) hybrid quadrupole orthogonal acceleration time-of-flight (Q-TOF) mass spectrometer provided detailed information about the mass distribution of the glycan derivatives. Collision-induced dissociation of the singly protonated [M + H](+) ions also gave rise to a number of product ions produced by the sequential cleavage of the glycosidic linkages. As fragmentation of the positively charged species occurred predominantly in one direction, i.e., from the non-reducing end of the glycan to the AA-Ac moiety, a considerable amount of information could be obtained with ease about the sequence in which the sugar residues were attached to one another. This derivatisation procedure and mass spectrometric methodology were applied successfully to neutral and acidic glycans released from proteins separated by gel electrophoresis.

Evaluation of the effect of an AIDS prevention program on high school students' sexual risk-taking behavior.

The study evaluated the effects of an AIDS prevention program on 179 high school students' sexual risk-taking behavior. Young actors role modeled behaviors to reduce the risk of AIDS. Sexual risk-taking behavior was assessed prior to and 3 months after attending the program. The pre-test mean sexual risk-taking score was 1.8 (SD = 3.5) with 0 to 30 as the potential range. There were significant differences between pre- and post-test sexual risk-taking behavior for the low-risk group (< or = 1.8), Wilcoxon (127) = -4.5, p = .000, and high-risk group (> 1.8), Wilcoxon (52) = -2.2, p = .03. Findings suggest support for role modeling strategies in decreasing sexual risk-taking behavior among high school students.

Effects of paced mating on c-fos gene expression in the female rat brain.

When estrous female rats control or pace (P) their sexual contacts with males, several neuroendocrine and behavioral responses to mating occur that are not observed or are greatly attenuated after nonpaced mating. The present study examined whether the distribution and amount of FOS immunoreactivity (FOS-IR) induced in brain by mating would be altered in females receiving paced rather than nonpaced mating stimulation. In the first experiment, females received 5 or 15 intromissions during paced mating tests (5P and 15P), 5 or 15 intromissions during nonpaced mating tests (5NP and 15NP), 15 mounts-without-intromission (MO) or remained in their homecages (HC). Selective increases 1 h after paced mating stimulation were observed in the posterodorsal medial amygdala (MePD), where significantly more FOS-IR cells were present in the 5P and 15P groups than in the respective NP groups. The 5P, 5NP and 15NP had significantly more FOS-IR than the HC, MO, and 5NP groups, and the 5P group had levels of FOS-IR which were equivalent to that seen in the 15NP group. In the posteromedial portion of the bed nucleus of the stria terminalis (BNSTpm) and the ventrolateral portion of the ventromedial nucleus of the hypothalamus (VMHvl), paced mating induced significantly greater numbers of FOS-IR cells than did either MO or HC treatments; increases induced by nonpaced mating were not statistically greater than HC controls. No differences between groups were seen in the medial preoptic area (mPOA). In the second experiment, experimentally lengthening the interintromission interval (III) as well as increasing the intromission duration to mimic the characteristics of paced mating, resulted in significant increases in FOS-IR in the MePD but not in the other three brain regions. These results demonstrate that paced mating is more effective in inducing c-fos expression than nonpaced mating, and that the MePD is particularly sensitive to differing characteristics of the mating stimuli received.

Iodine-123-5-iodo-6-nitroquipazine: SPECT radiotracer to image the serotonin transporter.

UNLABELLED: Because serotonergic function has been implicated in the pathophysiology of a number of diseases of the nervous system, efforts to image this system in vivo have received considerable recent attention. Promising preliminary results with the tracer 5-iodo-6-nitroquipazine (INQUIP) have prompted us to perform further studies designed to validate the use of the tracer as an in vivo ligand for the serotonin transporter. METHODS: We studied six adult macaca mulatta in eight experiments which involved SPECT imaging at 17 to 24 hr post-tracer injection, including three experiments with coinjection of the 123I-and 125I-radiolabeled tracer for direct comparison of autoradiography and SPECT, and three experiments in which animals were lesioned with the serotonergic neurotoxin (+/-)3,4-methyl-enedioxymethamphetamine (MDMA). In addition, we evaluated the metabolism of the tracer in the brain and periphery. RESULTS: SPECT images obtained at 17 and 24 hr reflected the known pattern of distribution of serotonin transporters and also showed close correspondence to the autoradiograms. Ratios of binding in the brain-stem to binding in the cerebellum were close to 3 at 17 hr. autoradiograms from an MDMA-treated animal showed up to 95% reductions of binding, while the SPECT data showed smaller reductions. Virtually all of the tracer in the brain stem was in the form of unmetabolized parent compound, but plasma showed rapid peripheral metabolism of the tracer. CONCLUSION: These results demonstrate that INQUIP SPECT images are sensitive measures of in vivo binding to the serotonin transporter, and support the further development of the tracer as a method for the in vivo study of serotonergic neurons in humans.

PET studies of cerebral glucose metabolism in conscious rhesus macaques.

A growing body of evidence suggests that rhesus macaques may be a good model of human brain aging. We used positron emission tomography (PET) and 18F-fluorodeoxyglucose (FDG) to measure regional cerebral metabolic rates for glucose (rCMRglc) in young and aged rhesus macaques to determine if age-related decreases, such as those reported in humans, also occur in macaques. Whereas the aged animals had lower metabolic rates in every brain region studied, the largest differences were in left temporal cortex. The largest differences were also observed in left temporal cortex when relative rCMRglc values were used. Both rCMRglc and relative rCMRglc were marked by substantial individual variation within the aged group. This variation may parallel the variation observed in behavioral studies. Future studies that include both PET and behavioral measures should help determine if there is a relationship between age-related changes in rCMRglc and behavior.

An exploratory study of righting reactions from a supine to a standing position in adults with Down syndrome.

BACKGROUND AND PURPOSE: Standing from a supine position is important for physical independence. The purpose of this study was to determine the developmental level of movement in this righting task of adults with Down syndrome. SUBJECTS: Fifteen subjects (mean age = 37.6 years, SD = 18, range = 22-65) with a diagnosis of Down syndrome and mild to moderate mental retardation participated in this study. METHODS: Subjects were videotaped rising from a supine to a standing position during 10 repeated trials. The video record was analyzed to categorize the standing movements according to VanSant's descriptions. RESULTS: Sixty-four percent of the upper-extremity movements, 14.6% of the axial component movements, and 33.8% of the lower-extremity movements could not be categorized according to VanSant's descriptions. Additionally, developmentally less advanced movements dominated those movements that could be categorized. CONCLUSION AND DISCUSSION: The great variety of movements demonstrated by these subjects in the task of standing from a supine position suggests greater motor maturity than is apparent from the movement sequences described by VanSant. Identifying appropriate standing movements in persons with Down syndrome will require weighing numerous intrinsic factors (eg, physiological and anthropometric) other than motor maturity.

Historical review of menstrual toxic shock syndrome.

This article reviews the history of Toxic Shock Syndrome and its relationship to tampons as well as governmental regulation of the tampon product. The historical antecedents and factors leading to governmental regulation will be addressed.

In vivo imaging of the 5-hydroxytryptamine reuptake site in primate brain using single photon emission computed tomography and [123I]5-iodo-6-nitroquipazine.

Previous experiments have demonstrated that 5-iodo-6-nitro-2-piperazinylquinoline (5-I-6-NQP) is a potent and selective ligand for studying brain 5-hydroxytryptamine (5-HT) reuptake sites. We performed in vivo imaging in non-human primates using single photon emission computed tomography (SPECT) and the 123I-labeled compound [123I]5-I-6-NQP. These studies showed rapid brain uptake, with slow egress of the tracer from the brainstem, a region rich in 5-HT reuptake sites. Loss of the tracer from regions with a lower density of these sites, such as cerebellum, was relatively more rapid. Pretreatment of animals with paroxetine increased the washout of tracer from the brainstem to rates similar to that seen in cerebellum. Brainstem to cerebellar ratios of tracer accumulation were > 2 by 8 h after injection, and in paroxetine pretreated animals remained close to 1. These results indicate that the radiotracer has characteristics suitable for use as a SPECT imaging agent of serotonin reuptake sites.

[125I]5-iodo-6-nitroquipazine: a potent and selective ligand for the 5-hydroxytryptamine uptake complex. II. In vivo studies in rats.

The in vivo regional distribution and pharmacological profile of [125I]5-iodo-6-nitroquipazine in the rat brain were studied to evaluate this compound as a potential in vivo imaging agent of the 5-hydroxytryptamine (serotonin or 5-HT) uptake complex. This radioligand penetrated the blood-brain barrier quickly and efficiently, with 1.9% of injected dose found in the whole brain at 5 min post i.v. injection. The regional brain distribution of radioactivity at time points later than 2 h was highly correlated with the known distribution of serotonin uptake sites and terminals. Coadministration of 2 mg/kg paroxetine inhibited > 90% of the total in vivo binding of [125I]5-iodo-6-nitroquipazine. Other serotonin uptake inhibitors, such as fluoxetine and sertraline, were also effective inhibitors of [125I]5-iodo-6-nitroquipazine brain binding in vivo. Non-serotonergic uptake blockers (desipramine, nomifensine, and GBR-12909) and the postsynaptic serotonin receptor agent LSD had no effect on [125I]5-iodo-6-nitroquipazine binding in vivo even at high doses. Lesioning of the serotonergic system by p-chloramphetamine produced approximately 90% decrease in specific in vivo binding. Extraction and analysis of brain radioactivity indicated that approximately 95% of the extractable radioactivity was unmetabolized [125I]5-iodo-6-nitroquipazine. These results indicate that [125I]5-iodo-6-nitroquipazine is a specific, useful radioligand for studying serotonergic uptake sites and terminals in animals, and an 123I-radiolabeled form of the drug would be an excellent candidate for non-invasive single photon emission computed tomography (SPECT) imaging of these sites in the living human brain.

Attributions for rapid or slow recovery from sports injuries.

Sport participants (n = 276) stated the most likely cause of rapid or slow recovery from injury and rated that causal factor along several dimensions. Examination of the open-ended responses suggested that four general types of attributions were utilized by the athletes: personal factors, injury-related factors, treatment-related factors, and situational factors. Analysis of dimensional ratings indicated: (a) causes of slow recovery were consistently perceived as less stable, controllable, global, and intentional than causes of rapid recovery; (b) causes of slow recovery were sometimes perceived as more internal than causes of rapid recovery; and (c) physical self-esteem interacted with gender to influence dimensional ratings of the attributions. These findings were discussed in relation to the motivational significance of causal interpretations during recovery and in relation to the model of stress and athletic injury presented by Andersen and Williams (1988).