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Behav Neu- region in the integration of circulating function and emotion rosci 1990;104:44–55 discount zoloft 50mg with mastercard. Synaptic plasticity in fear condition- feature inhibition in a feature-negative discrimination buy discount zoloft 50mg on-line. J Exp ing circuits: induction of LTP in the lateral nucleus of the amyg- Psychol Anim Behav Process 1994;20:51–65 cheapest zoloft. Face processing impair- ation of aversive behaviour in the mouse purchase zoloft with mastercard. Br J Pharmacol 1989; ments after encephalitis: amygdala damage and recognition of 96:325–332. Mesial temporal neurons in the macaque lesions of the basolateral amygdala abolish the expression of monkey with responses selective for aspects of social stimuli. The NMDA receptor antagonist MK- conscious rats: effects on blood pressure, heart rate and plasma 801 blocks acquisition and extinction of conditioned hypoalge- catecholamines. New York: Grosset/Putnam, tioned heart rate and eyeblink responses produced by hippocam- 1994. Neurobiology of fear responses: the role of the amyg- 1980;30:20–38. Characterization of preten- interactions in the ventral striatum: role in locomotor activity torial periaqueductal gray matter neurons mediating intraspe- and responding with conditioned reinforcement. Psychopharma- cific defensive behaviors in the rat by microinjections of kainic cology 1994;115:516–528. Chapter 64: Neural Circuitry of Anxiety and Stress Disorders 947 68. Longitudinal neuronal organi- to noise stress in the spontaneously hypertensive rat. Brain Res zation of defensive reactions in the midbrain periaqueductal 1984;291:249–259. Quiescence and hyporeactivity amygdala central nucleus on heart rate conditioning in rabbits. Inhibition and learning: pavlovian conditioning in in the amygdala central nucleus on conditioned heart rate. Interactions between the ment of EPSP and NMDA receptor-mediated synaptic trans- amygdala and ventral striatum in stimulus-reward associations: mission in the amygdala. Second order fear conditioning prevented Neuroscience 1989;30:63–75. Application of pavlovian higher-order further evidence of limbic-striatal interactions underlying re- conditioning to the analysis of the neural substrates of learning ward-related processes. The nucleus accum- freezing, but not contextual 'blocking' of fear-potentiated star- bens if not critical for condtioned inhibition of fear as measured tle after lesions of the dorsal hippocampus. Is the hippocampus neces- potentiated startle: blockade by infusion of an NMDA antago- sary for contextual fear conditioning? Effects of lesions tinction of fear-potentiated startle using a visual conditioned to the hippocampus on contextual fear: evidence for a disruption stimulus. The midbrain periaqueductal gray as a coordina- ing. The midbrain periaqueductal gray matter: func- Aggleton JP, ed. The amygdala: neurobiological aspects of emotion, tional, anatomical and neurochemical organization. The role of the amygdala in system responsible for fear. Psychonom Bull Rev 1994;1: the expression of psychic phenomena in temporal lobe seizures. The excitatory effects of the amygdala North Holland, 1981:489–507. Psychol Bull 1964; diated by hypothalamic norepinephrine, serotonin, and CRF- 62:89–109. Different regions of the periaqueductal grey are in- amygdala in the coordination of behavioral, neuroendocrine, volved differently in the expression and conditioned inhibition and prefrontal cortical monoamine responses to psychological of fear-potentiated startle. Dissociable effects of selective lesions is involved in the sensitization of the acoustic startle response to hippocampal subsytems on exploratory behavior, contextual in rats. Partial anxiolytic actions of morphine sul- 487–493. Bilateral lesions of the amygdala attenuate Res 1993;58:123–131. Role of amygdaloid nuclei in the anxiolytic Res 1994;648:215–221. The effects of neurotoxic related responses in the rat. An infusion of bupivacaine 948 Neuropsychopharmacology: The Fifth Generation of Progress into the nucleus accumbens disrupts the acquisition but not the 129. Postsynaptic induction and PKA- expression of contextual fear conditioning. Behav Neurosci 1999; dependent expression of LTP in the lateral amygdala. Medial amygdala enhances rats: reinstatement of conditioned performance by noxious stim- synaptic transmission and synaptic plasticity in the dentate gyrus ulation on test. Attenuated hippocampal long-term mediates context-specific extinction of learned fear. Psychophar- potentiation in basolateral amygdala-lesioned rats. Amygdala N-methyl-D-aspartate not impair pavlovian fear conditioning but regulates when and receptors participate in the induction of long-term potentiation where fear is expressed. J Exp Psychol Anim Behav Process 1999; in the dentate gyrus in vivo. Neurotoxic lesions of basolateral amygdala facilitates the induction of long-term po- basolateral, but not central, amygdala interfere with pavlovian tentiation in the dentate gyrus in vivo. Neurosci Res 1995;22: second-order conditioning and reinforcer devaluation effects. Norepinephrine infused into the ba- neuron activity for the induction of long-term potentiation in solateral amygdala posttraining enhances retention in the spatial the dentate gyrus in vivo. Anxiolytic-like action of vation detected with echo-planar functional magnetic resonance neuropeptide Y: mediation by Y1 receptors in amygdala, and imaging. Intrinsic neurons in sive consequences of morphine withdrawal. Behav Pharmacol the amygdala field projected to by the medial geniculate body 1995;6:74–80. Disorders of facial recognition, social behaviour and rats via direct neurotropic action. Neural encoding of individual tractotomy: a clinical and experimental study. Psychol Med words and faces by the human hippocampus and amygdala. The amygdala is essential for the expression of nucleus lesions: effect on heart rate conditioning in the rabbit. Effects of electrical stimula- performance of conditional fear. Physiol Behav 1992;51: tion of the amygdaloid central nucleus on neocortical arousal 1271–1276. Stress-induced hypoalgesia and defensive freez- 141. Amygdaloid contribu- ing are attenuated by application of diazepam to the amygdala. Antinociception emotion, memory and mental dysfunction. New York: Wiley–Liss, following opioid stimulation of the basolateral amygdala is ex- 1992:229–254. Neurocomputation and learning: foundations Physiol Psychol 1980;94:313–323. 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B: Logical images showing anatomical overlap of significant changes com- the brain distribution of a radiotracer that binds selectively mon to both experiments purchase zoloft with a visa. Top row: Concordant areas with in- at the receptor (or transporter) order zoloft with paypal. In many applications a brain creased flow during sadness and decreased metabolism during region is identified and a time–activity curve for that region remission 50 mg zoloft with visa. Bottom row: Areas with decreased flow during sadness and increased metabolism during remission purchase 25mg zoloft. Multiple factors directly influ- mann area designations. Red indicates ence the amount of tracer that accumulates in any given changes unique to sadness; dark blue indicates changes unique brain region: concentration of receptors (Bmax), dissociation to remission of depression; lighter blue indicates changes com- constant between the receptor and ligand (Kd), and nonspe- mon to both. Arrows signify direction of change associated with each condition. In addition, the amount of uptake in the entire brain is dependent on the level of radiotracer in plasma and the degree to which the radiotracer nonspecifically binds to plasma proteins. To measure the Bmax separately from Kd, the experiment must include some measurements with par- tial saturation of the receptors; this is rarely done for both logistical and ethical reasons. To address this issue, Mintun and associates (124) proposed a term binding potential (BP) 1074 Neuropsychopharmacology: The Fifth Generation of Progress that combined both terms in the form BP Bmax/Kd. The ing has significantly slowed research in affective disorders. In the 5-HT2A system some initial work in tal conditions or the different patient populations, the BP depression was done using tracers with limited selectivity. Since these initial reports, meth- specific binding. A second requirement for calculation of odologic development to image 5-HT2A receptors has BP is that the kinetics of receptor–ligand interaction be been successful using highly selective agents including distinguishable from the transport kinetics into the brain. However, when The application of these radioligand techniques in mood both processes are of similar rates the BP is difficult to disorders has begun with some interesting results. Biver and calculate and an alternative term, the distribution volume associates (29) found apparent decreased [18F]altanserin (DV) has been proposed (125). Conceptually, the DV of a binding in the right insular and adjacent orbital cortices in given brain region equals the ratio of brain activity divided eight medication-free depressed patients. However, as the by plasma activity at equilibrium and includes the effects data processing approach normalized for global [18F]altans- of both specific and nonspecific binding. The DV also can erin uptake the method cannot distinguish between a true be calculated as a parametric image in which each pixel is decrease and an increase that is proportionally less than the assigned the appropriate calculated DV value (126). As the [18F]altanserin binding in the remaining brain. Nonethe- DV includes the effect of both specific and nonspecific less, the detection of a regional change in [18F]altanserin binding, the DV is usually 'corrected' by dividing by the binding suggests some type of regional difference in receptor DV of a region where only nonspecific binding occurs. Several other studies, however, have not shown al- result, the DVratio, is a frequent form of reporting PET and tered radioligand binding to 5-HT2A receptors during SPECT receptor data. Meyer and co-workers (133) used [18F]setoper- ratio when the DV values for the areas of interest are not actually one to compare 14 medication-free depressed patients with calculated from kinetic or equilibrium data, but are esti- 19 control subjects and found no difference in binding in mated from single images. The single image is usually stan- a large prefrontal cortex region of interest. The data was dardized as being at a given time after injection of tracer reported as DVratio and quantitation using plasma activity but may be highly susceptible to individual differences in was not done. Interestingly, the prefrontal cortex value was plasma clearance or transport into the brain. Further complicating the use of the DVratio is that it is After correction of the DVratio to yield a term proportional occasionally mistaken as being proportional to Bmax and to receptor density (the BP is proportional to DVratio BP. Actually, the BP is proportional to the term DVratio 1) this trend represents a rather large 25% decrease in the 1, which can be substantially different when the DVratio is depressed group. Finally, the calculation of DV and DV is usually Yatham and colleagues (134) used [18F]setoperone to ratio done without the measurement of plasma binding as it can measure 5-HT2A binding in 20 depressed and 20 controls. Indeed, the BP differs from the DVratio account for differences in nonspecific uptake and then pro- 1 only by the incorporation of the plasma binding into cessed using statistical parametric mapping (SPM). Thus, if plasma binding is unknown the use of tunately, the actual DV image was not calculated, nor the DVratio 1 is quite appropriate and will remove all individ- DVratio, as only raw PET activity from a single time frame ual and group effects of plasma binding in the receptor data. SPM performed a pixel-by-pixel ANCOVA to What is usually not appreciated is that individual variations detect pixels with significant group differences and showed in brain nonspecific binding are not corrected in the DVratio generalized decreased binding in the frontal and parietal 1 calculation. This limitation of the DVratio 1 term cortices of the depressed patient group. Yatham and col- is rarely discussed and even more rarely quantitatively exam- leagues reported that in some voxels the decrease in uptake ined. As the study was done without an equilib- The lack of suitable radioligands for human PET imag- rium state or kinetic analysis, it is unknown whether trans- Chapter 74: Imaging of Affective Disorders 1075 A B C D FIGURE 74. Parasagittal views through the head of the caudate of an anatomic magnetic resonance imaging scan and three different types of functional positron emission tomography scans. All images were collected in normal control subjects and have been converted to a standard atlas coordinate system using linear affine transformation. The upper right image is from a 60- second scan after injection with [15O]water and represents the distribution of cerebral blood flow (CBF). The lower left image is from a 30-minute scan obtained 30 minutes after injection of [11C]raclopride. The scan shows widespread low nonspecific binding (e. The lower right image is from a 30-minute scan obtained 60 minutes after injection of [18F]altanserin. Again, the cerebellum shows low nonspecific uptake, whereas the cortical gray matter shows the specific binding to the 5-HT2A serotonin receptors. These images demonstrate the ability to visualize distinct aspects of brain function using different radiotracers. Relatively high CBF is seen throughout the cerebellum and cortical and subcortical gray matter. In contrast, D2 receptors are seen to be highly concen- trated in the caudate, whereas 5- HT2A receptors are concentrated in the cortical gray matter with only small amount of receptor binding in basal ganglia. With the appropriate quantitative processing, these differences in radiotracer uptake can be expressed as relative or absolute recep- tor density. However, most of the patients were con- 2A pressed patients and seven age-matched controls. Regions currently being treated with benzodiazepines (six of seven), of interest over multiple cortical areas were used to measure which may have further confounded the results. Finally, radioligand uptake at a given time after injection and the Meltzer and colleagues (136) used [18F]altanserin to image data were normalized by first subtracting cerebellar activity eleven late-life depressed patients and age-matched controls. This result is a non- Logan graphical analysis was used to analyze regional activ- standard term that is not corrected for variations in plasma ity data and quantitate DV and the DVratio 1. Meltzer nonspecific binding (but may be corrected for variations and colleagues reported no difference between the depressed in brain nonspecific binding). However, valida- gional measures of 5-HT2A binding appear to yield slight, tion is problematic because there are few tools for verifying nonsignificant decreases in depressed populations compared rates of serotonin synthesis. The image-wide processing methods using synthetic rates appear to be highly dependent on plasma SPM, which had different methods of normalizing the ra- tryptophan levels. The work, likely using conventional analyses, is done. The authors suggest that this increase reflects de- 100,635 (137,138). The images are unusual because of the creased dopaminergic neurotransmission. Decreased synap- very high ratio of specific to nonspecific binding in the tic dopamine could then result in decreased occupancy of brain. Compared to images from labeled setoperone or al- the D2 receptors and D2 up-regulation, both factors could tanserin, in which approximately one-half of all of the brain lead to increased IBZM binding. In two other reports the activity is not bound to the receptor of interest, the IBZM uptake in the striatum was shown to decrease during [11C]WAY 100,635 PET images have less than 10% of the treatment with antidepressants (146,147), although de- activity in nonspecific binding and 90% specific activity. However, the striatal dopamine system may not assumed to be devoid of 5-HT1A receptors, is typically be the most critical in affective disorders. With the advent greater than 15, depending on the timing of the scan (com- of radioligands able to image extrastriatal D2 receptors (e.

If hematocrit is below 30% purchase 25mg zoloft, transfuse cross-matched blood (Amin 1993) purchase zoloft overnight. Common indications for central venous cannulation: measurement of mean central venous pressure order 50 mg zoloft fast delivery, large bore venous access zoloft 25 mg on line, administration of irritating drugs and or parenteral nutrition, hemodialysis, placement of a pulmonary artery catheter. Placement of a pulmonary artery catheter is indicated to obtain direct and calculated hemodynamic data that cannot be obtained through less invasive means (Sakr 2005). The goal for all critically ill patients is to provide adequate oxygen for cellular use through suitable oxygen consumption, which is variable between tissues, and the changes of the basal or active metabolic rate for each cell. Basic Hemodynamic Monitoring of Neurocritical Patients | 57 Oxygen delivery to tissues and organs responds to many local systemic variables to keep cellular homeostasis. Pulmonary artery balloon flotation catheter insertion may be necessary for full assessment of these parameters, and of evaluation of determinants of cardiac output and the oxygen content of circulating blood, on which oxygen delivery is dependent. In the presence of positive pressure ventilation with PEEP, central venous and pulmonary artery occlusion pressures may be falsely elevated and need to be interpreted with caution. The fluid challenge is the only way to interpret Central Venous Pressure (CVP) or Pulmonary Artery Occlusion Pressure (PAOP). Assessment of the determinants of cardiac output will proceed as follows: a. Heart rate and rhythm assisted by pulse oximeter and electrocardiogram. Preload assessed right and left heart; right heart through neck vein distension, liver enlargement and central venous pressure assessment; left heart through dyspnea on exertion, orthopnea, arterial blood pressure; pulmonary artery occlusion pressure and arterial pressure through waveform analysis (Sakr 2005). Afterload assisted by mean arterial blood pressure and systemic vascular resistance; contractility can be assessed by ejection fraction and echocardiography. As discussed earlier, the goal of hemodynamic monitoring in neurocritical care units is to assess the magnitude of physiological derangements in critically ill patients and to institute measures to correct the imbalance. Basic hemodynamic monitoring consists of clinical examination, invasive arterial monitoring, central venous pressure monitoring, hourly urine output, central venous oxygen saturation and echocardiography. Dynamic indices of fluid responsiveness such as the pulse pressure variation and stroke volume variation can guide 58 | Critical Care in Neurology decision making for fluid resuscitation. Cardiac output is traditionally measured using the pulmonary artery catheter; less invasive methods now available include the pulse contour analysis and arterial pulse pressure derived methods. It is essential to determine whether the hemodynamic therapy is resulting in an adequate supply of oxygen to the tissues proportionate to their demand. Mixed and central venous oxygen saturation and lactate levels are commonly used to determine the balance between oxygen supply and demand (Walley 2011). Neurocritical Monitoring Mervat Wahba, Nabil Kitchener, Simin Mansoor Neurocritical care relies on monitoring cerebral functions. Intracranial pressure monitoring may indicate high pressure in several acute neurological conditions. Massive stroke may cause life-threatening brain edema and occur in about 10% of patients with supratentorial stroke. Massive brain edema usually occurs between the second and the fifth day after stroke onset. Neuro-Specific Monitoring Accurate neurological assessment is fundamental for the management of patients with intracranial pathology. This consists of repeated clinical examinations (particularly GCS and pupillary response) and the use of specific monitoring techniques, including serial CT scans of the brain. This chapter provides an overview of the more common monitoring modalities found within the neurocritical care environment. A drop of two or more GCS points (or one or more motor points) should prompt urgent re-evaluation and a repeat CT scan. Eye opening is not synonymous with awareness, and can be seen in both coma and persistent vegetative state (PVS). The important detail is that the patients either open their eyes to a specific command or shows ability to fix eye on a specific target or follows a visual stimulus. Pupillary response Changes in pupil size and reaction may provide useful additional information: – Sudden unilateral fixed pupil: Compression of the third nerve, e. A reduction in sedation level will usually be at the suggestion of the Regional Neurosurgical Center (RNC) and its timing will depend upon a number of factors. Responses such as unilateral pupillary dilatation, extensor posturing, seizures, or severe hypertension should prompt rapid re-sedation, repeat CT scan, and contact with the RNC. In the patient with multiple injuries, consideration must be given to their analgesic requirements prior to any decrease in sedation levels. Invasive Monitoring Cerebral perfusion pressure (CPP) reflects the pressure gradient that drives cerebral blood flow (CBF), and hence cerebral oxygen delivery. Measurement of intracranial pressure (ICP) allows estimation of CPP. Sufficient CPP is needed to allow CBF to meet the metabolic requirements of the brain. An inadequate CPP may result in the failure of autoregulation of flow to meet metabolic needs whilst an artificially induced high CPP may result in hyperemia and vasogenic edema, thereby worsening ICP. The CPP needs to be assessed for each individual and other monitoring modality (e. Despite its almost universal acceptance, there are no properly controlled trials demonstrating improved outcome from either ICP- or CPP-targeted therapy. As such, ICP- and CPP- targeted therapy have become an accepted standard of care in head injury management. The 2007 Brain Trauma Foundation Guidelines (Brain Trauma Foundation 2007) recommend treating ICP values above 62 | Critical Care in Neurology 20 mmHg and to target CPP in the range of 50-70 mmHg. Patients with intact pressure autoregulation will tolerate higher CPP values. Aggressive attempts to maintain CPP >70 mmHg should be avoided because of the risk of ARDS. Although associated with a higher incidence of infection and greater potential for brain injury during placement, this remains the gold standard. Historically, saline could be injected to assess brain compliance. Extraventricular systems are placed in parenchymal tissue, the subarachnoid space, or in the epidural space via a burr hole. These systems are tipped with a transducer requiring calibration, and are subject to drift (particularly after long-term placement). Examples of extraventricular systems are the Codman and Camino devices. In general, both types of device are left in situ for as short a time as possible to minimize the risk of introducing infection. Indications for ICP monitoring In any case of head injury, if brain CT is positive for pathology, and the patient fulfills the criteria for use of a ventilator, Neurocritical Monitoring | 63 monitoring for intracranial pressure (ICP) becomes mandatory. The ICP device will generally be removed as soon as the patient is awake with satisfactory neurology (GCS motor score M5 or M6) or when physiological challenges (removal of sedation, normalizing PaCO2) no longer produce a sustained rise in ICP. Intracranial Pressure Waveforms and Analysis The normal ICP waveform is a modified arterial trace and consists of three characteristic peaks. The “percussive” P1 wave results from arterial pressure being transmitted from the choroid plexi, the “tidal” P2 wave varies with brain compliance, whilst P3 represents the dicrotic notch and closure of the aortic valve. It is important to establish the accuracy of the ICP trace and value before initiating therapy based upon the numbers generated. Transient sequential occlusion of the internal jugular veins or removing the head-up tilt should produce an increase in ICP. In addition to simple pressure measurement, if ICP is recorded against time, a number of characteristic wave forms (Lundeberg waves) can be seen. These may be seen in normal subjects, but are indicative of intracranial pathology when the amplitude increases above 10 mmHg. With cerebral autoregulation intact, a rise in MAP produces vasoconstriction and a fall in ICP. However, when autoregulation fails, the circulation becomes pressure passive and changes in Neurocritical Monitoring | 65 MAP are reflected in changes in the ICP. Continuous analysis of MAP and ICP allows a correlation coefficient called the pressure reactivity index to be derived (PRx).

We decided to recruit 32 schools to ensure that we had a minimum of 28 schools completing the trial purchase zoloft 50 mg, each with an estimated average of 35 children discount zoloft 100 mg with visa. The primary outcome measure of effectiveness was change in BMI SDS at 24 months buy zoloft in united states online. The secondary outcome measures included BMI SDS at 18 months discount zoloft express, waist circumference SDS, percentage body fat SDS and the percentage of children classified as underweight/ healthy weight, overweight and obese at 18 and 24 months with raw anthropometric measures being presented for completeness and comparison with other studies. Physical activity was measured using accelerometry and self-reported food intake scores using the validated Food Intake Questionnaire (FIQ) at 18 months, weekday and weekend. Outcome assessments Detailed standard operating procedures were created for the collection of each measure at each time point. Letters were sent home to parents at each assessment time point to remind them that measurements were going to take place. Within each cohort, all child-level measures were collected over an 8-week time period. Outcome assessments were completed: immediately post intervention in October/November 2013/14 (12 months post baseline) for the MLQ only, at 6 months post intervention in June/July 2014/15 (18 months post baseline), which included all behavioural and anthropometric measures; and at 12 months post intervention in October/November (24 months post baseline), which included only anthropometric measures. Anthropometric measurements (height, weight, percentage body fat and waist circumference) were undertaken by trained assessors, co-ordinated by the HeLP co-ordinator (all had completed enhanced Criminal Records Bureau/Disclosure and Barring Service checks). Outcome assessors completed refresher training before each data collection time point. The coefficients of variation to assess inter-rater reliability for height and waist circumference were 0. The independent outcome assessors were blinded to the allocation of schools. At 24 months post baseline, children were measured in their secondary school, and thus secondary school classes contained a mix of intervention and control children. If a child said something to reveal their group allocation, the assessor was asked to record, on the pro forma, that the measurement had been taken unblinded. The HeLP co-ordinators led the collection of the behavioural measures (FIQ and physical activity using accelerometry), as well of as the MLQ. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 15 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. TRIAL DESIGN AND METHODS Anthropometric measurements All anthropometric measures were collected over the course of 1 day in each school. If a child was absent on the day of measurement, up to three further attempts to collect their data were made for up to a further 2 weeks from the day of absence. Height was measured using a SECA stadiometer (Hamburg, Germany), recorded to an accuracy of 1 mm. Weight was measured using the Tanita Body Composition Analyser SC-330 (Tanita, Amsterdam, Netherlands). Percentage body fat was estimated from leg-to-leg bioelectric impedance analysis (using the Tanita Body Composition Analyser SC-330). Waist circumference was measured using a non-elastic flexible tape measure placed 4 cm above the umbilicus. We were mindful that, at baseline, the HeLP co-ordinator had yet to develop a working relationship with the children, so, to put the children at ease and minimise any possible stigmatisation of overweight or sensitive children, the collection of these measurements formed part of a specially designed lesson that was based around measuring in general and ways in which information can be presented. Each child, one at a time, left the classroom during the lesson to go to a private room and have their height, weight, waist circumference and percentage body fat by bioelectrical impedance measured by two other trained researchers. For the 18- and 24-month measurements, no special lesson took place, as the children were familiar with the measurement process and felt at ease with the HeLP co-ordinator, who co-ordinated the smooth running of the measurements in each school. At each data collection time point, the children had the option to decline one or more measurements. While the measurements were taken, the electronic reading was covered so that the child was unable to read their results. This process had been developed during the pilot phases to reduce any stigmatisation of overweight/obese and underweight children and to minimise any discussion about weight. Accelerometer measurements We used a wrist-worn triaxial accelerometer, called the GeneActiv,37 to objectively measure physical activity and sedentary time for a subset of the recruited children (one randomly selected class per participating school). These accelerometers are waterproof so they do not need to be removed for swimming or showering. We asked children to wear the accelerometer continuously (including at night) for 8 consecutive days on the wrist of their non-dominant arm. To assist with adherence, information packs were sent to parents 1 week before their child was fitted with the GeneActivs, providing information on wearing the accelerometer as well as guidance to be distributed to sports coaches to prevent the accelerometer being removed during sport. On the day the accelerometers were issued, the HeLP co-ordinator spoke to groups of 10 children about how to comply with the procedures, and answered any questions. Following recommended guidance, children were included in the analysis if they had at least 4 days (including a weekend day) of 10 hours of wear time on each of those days. This questionnaire was developed for children of the same age as those in this study, and it can be adapted to capture information on the consumption of a number of food groups, depending on the focus of an intervention (Dr Allan Hackett, Liverpool John Moores University, 21 September 2006, personal communication). We adapted the questionnaire so that we could focus specifically on healthy (10 items) and unhealthy (13 items) snacks and drinks, and negative (25 items) and positive (22 items) food markers. Children had to answer yes or no as to whether or not they had consumed each food item the previous day. A number of items make up each category to provide a total score from 16 NIHR Journals Library www. Questionnaire items, the scoring system and the tolerances for missing data can be seen in Appendix 2. Children completed the FIQ twice, at baseline and at 18 months, to allow the assessment of weekday (completed Tuesday to Friday) and weekend (completed on a Monday) food intake. The HeLP co-ordinator led the two lessons required for the children to complete the questionnaires at each time point. Children were arranged in literacy tables to ensure that assistance could be given as efficiently as possible. Support was also provided by an additional researcher, the class teacher and the teaching assistant. My Lifestyle Questionnaire The MLQ was designed to assess knowledge and a series of potential cognitive and behavioural mediators of any observed differences in outcome between the control and the intervention groups. The questionnaire included items designed to assess knowledge, self-efficacy, intentions, peer norms, family approval, attitudes towards restrictions on behaviour, parental provision and rules, goal-setting, self-monitoring and a range of relevant behavioural skills, including suggestions to and discussion with parents, shopping, cooking and trying new snacks. These items were derived from previous research applying the IMB and health action process models but tailored to the logic model underpinning the development of HeLP (see Appendix 3). School assessment Information on the school-level characteristics and policies on physical activity and nutrition adopted in each school was collected at baseline (October/November 2012/13) and at 18 months (June/July 2014/15) (see Appendix 4) using a questionnaire that was completed by a member of staff and/or an administrator. Index of Multiple Deprivation The Index of Multiple Deprivation (IMD) score was assigned to the lower super output area of each school and pupil as determined by their postcode. Changes to trial protocol There were two substantial amendments to the protocol during the course of the trial. The first amendment was to clarify the inclusion criteria to include schools who had one single Year 5 class but who may have had a second class that mixed Year 5 and Year 6 children. The second amendment related to schools allocated to cohort 2 of the study, which were due to start the study in September 2013 (cohort 1 schools started in September 2012). These schools were re-contacted in July 2013, at which time two indicated that their circumstances had changed and that they were no longer able (or eligible) to participate in the trial. Schools that had been placed on the waiting list were then contacted to establish if they were still willing and eligible to participate, of which two were. Given the possibility of selection bias in the two withdrawn schools and in terms of potential imbalance between intervention and control groups in school-level confounders (known and unknown), the 16 schools in cohort 2 (i. This was completed using a minimisation approach to ensure reasonable balance in the stratification factors between the allocated groups across the combined two cohorts. Statistical analysis A detailed analysis plan was developed by the Trial Management Group and approved by the TSC in November 2015. These amendments were approved by the TSC chairperson in September 2016. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 17 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. TRIAL DESIGN AND METHODS plan and a summary of the amendments are published on the NIHR Public Health Research programme website, along with the study protocol. All comparative analyses allowed for the clustered nature of the data (i.

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Lupus-like nephritis has been reported in children and adults with H IV infection in association with m em bra- nous discount zoloft generic, m esangial order zoloft on line, and intracapillary proliferative glom erular lesions [204] generic 100mg zoloft otc. IgA nephropathy Immune-complex glomerulopathies has been reported in association with H IV infection purchase zoloft on line. The occurrence of IgA nephropathy Proliferative glomerulonephritis m ay not be coincidental and is H IV-associated. Indeed, circulating im m une com plexes com - Membranous glomerulonephritis posed of idiotypic IgA antibody reactive with anti-H IV IgG or IgM were identified in two Lupus-like nephropathy patients, and the identical im m une com plex was eluted from the renal biopsy tissue of one Immunoglobulin A nephropathy patient studied [199,205]. Unlike H IV-associated glom erulosclerosis, H IV-associated IgA Hemolytic uremic syndrome, thrombotic nephropathy has been reported exclusively in white patients with early H IV infection thrombocytopenic purpura exhibiting m icroscopic or m acroscopic hem aturia, absent or m odest azotem ia, and slowly progressive disease [206]. Instances of intravascular coagulation related to TTP or H US are recognized with increased frequency and m ay be the first m anifestation of H IV infection, although m ost develop at a late stage of the disease. The cause of hem olytic urem ic syn- FIGURE 7-40 drom e/throm botic throm bocytopenic purpura (H US/TTP) in patients infected with H IV is Other nephropathies associated with HIV. Plasm a tissue plasm inogen activator is increased in patients infected with H IV A variety of immune-complex-mediated who have throm botic m icroangiopathy [207]. There is no association with Escherichia coli glomerulopathies have been documented in 0154:H 7 infection, and intercurrent infections have been dem onstrated in only one third of patients with HIV infection. Renal involvem ent in TTP usually is m inim al, whereas vascular and glom erular glomerular diseases associated with HIV involvement are more frequent and extensive in HUS and can lead to renal cortical necrosis. Almost all opportunistic infections seen in patients with AIDS may localize in the kidneys as m anifestations of system ic disease. However, rarely are these infections expressed clinically, and often Pathogens Neoplasms they are found at autopsy. Cytom egalovirus infection is the m ost com m on [209]. Nephrocalcinosis can occur in Nocardia Lymphoma association with pulm onary granulom atosis, M ycobacterium Cryptococcus Myeloma avium –intracellulare infection, or as a m anifestation of extrapul- Pneumocystis monary pneumocystis infection. Renal tuberculosis is a manifestation Mycobacterium of miliary disease. Johnson RJ, Couser W G: H epatitis B infection and renal disease: 16. Lai KN, Lai FM : Clinical features and natural history of hepatitis B ated glom erulonephritis: effect of -interferon therapy. Takekoshi Y, Tochim aru H , N agatta Y, Itam i N : 18. Lin CY: Clinical features and natural course of H BV-related glom eru- A, non-B hepatitis. Agnello V, Chung RT, Kaplan LM : A role for hepatitis C virus infec- random ized trials in the treatm ent of viral hepatitis C: effects of dose tion in type II cryoglobulinemia. Sarac E, Bastacky S, Johnson JP: Response to high-dose interferon- patients with essential m ixed cryoglobulinem ia. Ann Intern M ed after failure of standard therapy in M PGN associated with hepatitis 1992, 117:573–577. Disdier P, H arle JR, W eiller PJ: Cryoglobulinem ia and hepatitis C 22. Dam m acco F, Sansono D: Antibodies to hepatitis C virus in essential m ixed cryoglobulinem ia. Pereira BJG: H epatitis C infection and post-transplantation liver dis- ease. Galli M , M onti G, M onteverde A: H epatitis C virus and m ixed cryo- globulinem ias. Ferri C, Greco F, Longobardo G: Antibodies to hepatitis C virus in patients with m ixed cryoglobulinem ia. Hardy NM , Sandroni S, Danielson S, W ilson W J: Antibody to hepatitis with cryoglobulinem ic m em branoproliferative glom erulonephritis. N iu M T, Colem an PJ, Alter M J: M ulticenter study of hepatitis C 59:319–320. Renal Disease in Patients Infected with Hepatitis and Human Immunodeficiency Virus 7. Perit D ial virus (anti-H CV): prevalence in the sam e geographical area in dialysis Int 1992, 12:28–30. Chan TM , Lok ASF, Cheng IKP: H epatitis C infection am ong dialysis 40. Kidney am ong chronic dialysis patients in the south-east of France. J M ed Virol 1992, infection in renal dialysis patients in Glasgow. Barril G, Traver JA: Prevalence of hepatitis C virus in dialysis patients in high-risk Saudi groups. Jadoul M , Cornu C, Van Ypersele de Strihou C, et al. Pinto dos Santos J, Loureiro A, Cendoroglo M eto M , et al. O kuda K, H ayashi H , Yokozeki KEA: M ode of nosocom ial H CV and in the staff caring for them. N atov SN , Pereira BJG: H epatitis C infection in patients on dialysis. PCR analysis of hem odialysis tis C infection by polymerase chain reaction among hemodialysis ultrafiltrate and whole blood. M orales JM , Fernandez-Zatarain G, M unoz M A, et al. ASAIO Trans 1991, ture and outcom e allograft m em branous glom erulonephritis in renal 37:97–109. N atov SN , Pereira BJG: H epatitis C infection in patients on dialysis. LaQ uaglia M P, Tolkoff-Rubin N E, Dienstag JL, et al. Am J Kidney D is 1988, feron therapy on H CV infection of hem odialyzed patients. Kidney Int 1994, tions in renal transplant patients. M ahony JF: Long term results and com plications of transplantation: 110. 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