The High Frequency Component of Heart Rate Variability and Delta EEG Power during Sleep in Healthy Women and Women with Irritable Bowel Syndrome

Thesis (Ph.D.)--University of Washington, 2016-06

Dizziness and unsteadiness following whiplash injury: Characteristic features and relationship with cervical joint position error

Dizziness and/or unsteadiness are common symptoms of chronic whiplash-associated disorders. This study aimed to report the characteristics of these symptoms and determine whether there was any relationship to cervical joint position error. Joint position error, the accuracy to return to the natural head posture following extension and rotation, was measured in 102 subjects with persistent whiplash-associated disorder and 44 control subjects. Whiplash subjects completed a neck pain index and answered questions about the characteristics of dizziness. The results indicated that subjects with whiplash-associated disorders had significantly greater joint position errors than control subjects. Within the whiplash group, those with dizziness had greater joint position errors than those without dizziness following rotation (rotation (R) 4.5degrees (0.3) vs 2.9degrees (0.4); rotation (L) 3.9degrees (0.3) vs 2.8degrees (0.4) respectively) and a higher neck pain index (55.3% (1.4) vs 43.1% (1.8)). Characteristics of the dizziness were consistent for those reported for a cervical cause but no characteristics could predict the magnitude of joint position error. Cervical mechanoreceptor dysfunction is a likely cause of dizziness in whiplash-associated disorder.

Incorporating nerve-gliding techniques in the conservative treatment of cubital Tunnel syndrome

Objective: To discuss the diagnosis and treatment of a patient with cubital tunnel syndrome and to illustrate novel treatment modalities for the ulnar nerve and its surrounding structures and target tissues. The rationale for the addition of nerve-gliding techniques will be highlighted. Clinical Features: Two months after onset, a 17-year-old female nursing student who had a traumatic onset of cubital tunnel syndrome still experienced pain around the elbow and paresthesia in the ulnar nerve distribution. Electrodiagnostic tests were negative. Segmental cervicothoracic motion dysfunctions were present which were regarded as contributing factors hindering natural recovery. Intervention and Outcomes: After 6 sessions consisting of nerve-gliding techniques and segmental joint manipulation and a home exercise program consisting of nerve gliding and light free-weight exercises, a substantial improvement was recorded on both the impairment and functional level (pain scales, clinical tests, and Northwick Park Questionnaire). Symptoms did not recur within a 10-month follow-up period, and pain and disability had completely resolved. Conclusions: Movement-based management may be beneficial in the conservative management of cubital tunnel syndrome. As this intervention is in contrast with the traditional recommendation of immobilization, comparing the effects of both interventions in a systematic way is an essential next step to determine the optimal treatment of patients with cubital tunnel syndrome.

Is health care seeking for irritable bowel syndrome and functional dyspepsia a socially learned response to illness?

In a population-based study of 207 subjects with irritable bowel syndrome (IBS) or functional dyspepsia (FD) and controls (n = 100), we aimed to determine whether dimensions of abnormal illness behavior from the Abnormal Illness Behaviour Questionnaire and aspects of social learning of illness behavior from the Social Learning of Illness Behaviour scale were independent predictors of health care seeking for IBS and FD. Results showed that dimensions of abnormal illness behavior and aspects of social learning of illness behavior (encouragement, reinforcement, and modeling) did not significantly differentiate between consulters and nonconsulters with IBS and/or FD. The Disease Conviction scale (OR = 1.55; 95% CI, 1.15-2.09) of the Abnormal Illness Behaviour Questionnaire was an independent predictor of having a diagnosis of IBS and/or FD, independent of age and gender, psychiatric diagnoses, and symptom severity. We conclude that a belief in the presence of serious pathology characterizes community subjects with IBS and FD, but not health care seeking.

Predictors of responsiveness to physiotherapy management of cervicogenic headache

A recent randomized controlled trial tested the effectiveness of therapeutic exercise and manipulative therapy on 200 subjects with cervicogenic headache. Although treatments were efficacious, 25% of patients did not achieve a clinically acceptable outcome - 50% reduction in headache frequency This study aimed to identify predictors from variables in subjects' demographics and headache history which might identify those who did or did not achieve a 50-79% or 80-100% reduction in headache immediately after the active treatments and 12 months postintervention. The results revealed no consistent pattern of predictors, although the absence of light-headedness indicated higher odds of achieving either a 50-79% [odds ratio (OR) = 5.45) or 80-100% (OR = 5.7) reduction in headache frequency in the long term. Headaches of at least moderate intensity, the patient's age and chronicity of headache did not mitigate against a successful outcome from physiotherapy intervention.

Fat as an endocrine organ: Relationship to the metabolic syndrome

Obesity and the metabolic syndrome have both reached pandemic proportions. Together they have the potential to impact on the incidence and severity of cardiovascular pathologies, with grave implications for worldwide health care systems. The metabolic syndrome is characterized by visceral obesity, insulin resistance, hypertension, chronic inflammation, and thrombotic disorders contributing to endothelial dysfunction and, subsequently, to accelerated atherosclerosis. Obesity is a key component in development of the metabolic syndrome and it is becoming increasingly clear that a central factor in this is the production by adipose cells of bioactive substances that directly influence insulin sensitivity and vascular injury. In this paper, we review advances in the understanding of biologically active molecules collectively referred to as adipokines and how dysregulated production of these factors in obese states mediates the pathogenesis of obesity associated metabolic syndrome.

Effect of knee joint angle on motor unit synchronization

Activity of the vasti has been argued to vary through knee range of movement due to changes in passive support of the patellofemoral joint and the relative contribution of these muscles to knee extension. Efficient function of the knee is dependent on optimal control of the patellofemoral joint, largely through coordinated activity of the medial and lateral quadriceps. Motor unit synchronization may provide a mechanism to coordinate the activity of vastus medialis (VMO) and vastus lateralis (VL), and may be more critical in positions of reduced passive support for the patellofemoral joint (i.e., full extension). Therefore, the aim of this study was to determine whether the degree of motor unit synchronization between the vasti muscles is dependent on joint angle. Electromyographic (EMG) recordings of single motor unit action potentials (MUAPs) were made from VMO and multiunit recordings from VL during isometric contractions of the quadriceps at 0 degrees, 30 degrees, and 60 degrees of knee flexion. The degree of synchronization between motor unit firing was evaluated by identification of peaks in the rectified EMG averages of VL, triggered from MUA-Ps in VMO. The proportion of cases in which there was a significant peak in the triggered averages was calculated. There was no significant difference in the degree of synchronization between the vasti at different knee angles (p = 0.57). These data suggest that this basic coordinative mechanism between the vasti muscles is controlled consistently throughout knee range of motion, and is not augmented at specific angles where the requirement for dynamic control of stability is increased. (D 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Neurophysiology of CSWS-associated cognitive dysfunction

The phenomenon of continuous spikes and waves during slow-wave sleep (CSWS) is associated with a number of epileptic syndromes, which share a behavioral phenotype characterized by deterioration of cognitive, behavioral, or sensorimotor functions. Available evidence seems to suggest that spike-wave activity is a result of a complex interaction between cortical and subcortical inhibitory networks and can "per se" produce a transient loss of underlying cortical functions. Syndromes like Landau-Kleffner syndrome, CSWS, and phenomena such as negative myoclonus could share in common--at least at the neurophysiological level--some similarities. Differences in behavioral phenotypes could be explained in term of maturational and genetic differences, as well as by the functional specificity of the involved areas.

Radioimmunoassay of insulin and glucagon with studies on the obese hyperglycaemic syndrome in mice

Sensitive and precise radioimmunoassays for insulin and glucagon have been established. Although it was possible to employ similar precepts to the development of both hormone assays, the establishment of a reliable glucagon radioimmunoassay was complicated by the poor immunogenicity and instability of the peptide. Thus, unlike insulin antisera which were prepared by monthly injection of guinea pigs with crystalline insulin emulsified in adjuvant, the successful production of glucagon antisera was accomplished by immunisation of rabbits and guinea pigs with glucagon covalently linked to bovine plasma albumin. The conventional chloramine-T iodination with purification by gel chromatography was only suitable for the production of labelled insulin. Quality tracer for use in the glucagon radioimmunoassay was prepared by trace iodination, with subsequent purification of monoiodinated glucagon by anion exchange chromatography. Separation of free and antibody bound moieties by coated charcoal was applicable to both hormone assays, and a computerised data processing system, relying on logit-log transformation, was used to analyse all assay results. The assays were employed to evaluate the regulation of endocrine pancreatic function and the role of insulin and glucagon in the pathogenesis of the obese hyperglycaemic syndrome in mice. In the homozygous (ob/ob) condition, mice of the Birmingham strain were characterised by numerous abnormalities of glucose homeostasis, several of which were detected in heterozygous (ob/+) mice. Obese mice exhibited pancreatic alpha cell dysfunction and hyperglucagonaemia. Investigation of this defect revealed a marked insensitivity of an insulin dependent glucose sensing mechanism that inhibited glucagon secretion. Although circulating glucagon was of minor importance in the maintenance of hyperinsulinaemia, lack of suppression of alpha cell function by glucose and insulin contributed significantly to both the insulin insensitivity and the hyperglycaemia of obese mice.

Causal attributions in King-Kopetzky syndrome

At least 10% of people who present for help with hearing difficulties will be found to have normal hearing thresholds. These cases are clinically categorized as King-Kopetzky syndrome (KKS), obscure auditory dysfunction (OAD), or auditory processing disorder (APD). While recent research has focussed on the possible mechanistic basis for these difficulties, the perceptions of the hearing difficulties that lead people to seek help have not hitherto been identified. This study presents findings from an observational survey of causal attributions of hearing difficulties from 100 people with KKS. The findings suggest that participants regard immunity and risk related causes of hearing difficulties as pre-dominant. Psychological factors were not considered to be causal for hearing difficulties. These factors were not affected by diagnostic classification. These findings inform audiologists about their patient beliefs for the first time. The authors suggest that clinicians take care to ensure that their counselling is responsive to these beliefs. © 2010 British Society of Audiology, International Society of Audiology, and Nordic Audiological Society.

Illness perceptions and hearing difficulties in King-Kopetzky syndrome:what determines help seeking?

The present study explored illness perceptions of hearing difficulties amongst one hundred participants who reported experiencing hearing difficulties despite normal audiometric thresholds. This experience is referred to as King-Kopetzky syndrome (KKS), obscure auditory dysfunction (OAD), or auditory processing disorder (APD). Logistic regression was used to consider the associations between help-seeking and a range of audiological and illness perception measures. Results indicate that help-seekers present with poorer speech in noise thresholds than non help-seekers, and that coherent illness perceptions and a negative belief in the consequences of hearing difficulties are associated with help-seeking status, regardless of hearing sensitivity.

Associação da depressão e distúrbio do sono em pacientes com e sem disfunção temporomandibular

Objective: To evaluate the inter-relationship between TMD (temporomandibular disorder), depression and sleep disorder. Methods: This is a case-control study with questionnaires in 111 patients, allocated from the Dentistry Department of UFRN, Natal, Brazil, from September 2014 to June 2015, for evaluation of depressive symptoms through the BDI (Beck Depression Inventory); sleep disorder, the PSQI (Pittsburgh Sleep Quality Index) and DTM through the RDC / TMD (diagnostic criteria to search for DTM). All indexes were applied by a single examiner previously trained and calibrated. The collected data were analyzed with chi-square tests of Pearson (χ2) and the unconditional logistic regression. Results: women had a risk of 2.85 times more likely to develop TMD (p = 0.046). The OR (odds ratio) shows that sleep disturbance increases by 2.19 the chances of having TMD (p = 0.062) and depressive symptoms increase the risk by 3.16 times in developing dysfunction (p = 0.053). Conclusion: The data of this research allows us to conclude that patients with TMD, in this population, were more likely to develop changes in sleep and depressive symptoms.

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings.

This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette's syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader-Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

Assessing the immune phenotype of cardiac syndrome x: a prospective study of biomarkers

Cardiac Syndrome X (CSX), the presence of angina pectoris with objective signs of myocardial ischaemia despite angiographically normal epicardial coronary arteries, appears to be due to coronary microvascular dysfunction and is known to be associated with an elevation of several inflammatory biomarkers, suggesting a possible role for inflammation in its pathogenesis. We aimed to further characterise this relationship by prospectively analysing a wide variety of molecular biomarkers in a cohort of CSX patients thereby charting the changes in biomarkers throughout the natural history of CSX from its initial diagnosis to eventual disease quiescence. We found that CSX patients, when compared to healthy controls, have a persistent low-grade systemic inflammatory response characterised by an elevation of Tumour Necrosis Factor and Interferon-gamma, regardless of the presence of contemporaneous signs or symptoms of disease activity. Interleukin-6 and C-reactive Protein (CRP) are only elevated when patients have clinical evidence of disease activity and may be state markers in CSX. Moreover, CRP levels appear to correlate with signals of disease severity such as the time taken to develop symptoms during exercise stress testing. We have also demonstrated that the enzyme Indoleamine-2,3- dioxygenase is upregulated in active disease thus providing a possible explanation for the increased burden of psychological disease encountered in CSX. Analysis of the microRNA transcriptome showed that miR-143 is significantly under-expressed in CSX patients. This could allow phenotype switching in vascular smooth muscle cells with the resultant vascular remodelling causing reduced vessel responsiveness to local rheological stimuli and reduced luminal diameter with consequent increased microvascular resistance during times of increased myocardial oxygen demand, thereby limiting maximal hyperaemia during exercise. Our findings corroborate many previous hypotheses regarding the role of inflammation in CSX, generate new insights into possible pathogenic mechanisms and offer new therapeutic targets for the future management of this important cardiological condition.

Shiftwork, sleep disturbance and the metabolic syndrome among female hospital workers

Background: Shiftwork is associated with increased sleep disturbance and cardiovascular and metabolic disease risk. This thesis will focus on shiftwork-related sleep disturbance and the potential mediating role of reduced sleep duration in the relationship between a current rotational shiftwork schedule and the metabolic syndrome among female hospital employees. Objectives: 1) To describe sleep patterns in relation to different shiftwork exposure metrics (current status, cumulative exposure, number of consecutive night shifts); 2) To assess the association between shiftwork metrics and sleep duration; 3) To determine whether sleep duration on work shifts mediates the relationship between a current rotational shiftwork pattern and the metabolic syndrome; and 4) To assess whether cumulative shiftwork exposure and the number of consecutive night shifts are associated with the metabolic syndrome. Methods: 294 female hospital employees (142 rotating shiftworkers, 152 dayworkers) participated in a cross-sectional study. Shiftwork parameters were determined through self-report. Sleep was measured for one week with the ActiGraph GT3X+, a tri-axial accelerometer. The metabolic syndrome was defined according to the Joint Interim Studies Consensus Statement. Sleep was described by shiftwork exposure parameters, and multivariable linear regression was used to determine associations between shiftwork variables and sleep duration. Regression path analysis was used to assess whether sleep duration was a mediator between a current shiftwork schedule and the metabolic syndrome, and the significance of the indirect (mediating) effect was tested with bootstrap confidence intervals. Logistic regression was used to determine associations between cumulative shiftwork exposure, number of consecutive night shifts, and the metabolic syndrome. Results: Current shiftworkers slept less on work shifts, more on free days, and were more likely to nap compared to dayworkers. Sleep duration on work shifts was a strong intermediate in the relationship between a current shiftwork pattern and the metabolic syndrome. Cumulative shiftwork exposure and the number of consecutive night shifts did not affect sleep or the metabolic syndrome. Conclusions: A current shiftwork pattern disrupts sleep, and reduced sleep duration is an important intermediate between shiftwork and the metabolic syndrome among female hospital employees.