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Biomedical subjects

P Chappell

Publications and source records attributed to P Chappell.

8 recordsLinked to original sources
PubMed1996

Elevated cerebrospinal fluid corticotropin-releasing factor in Tourette's syndrome: comparison to obsessive compulsive disorder and normal controls.

Stress- and anxiety-related fluctuations in tic severity are cardinal features of Tourette's syndrome (TS), and there is evidence for involvement of noradrenergic mechanisms in the pathophysiology and treatment of the disorder. To examine further the pathobiology of this enhanced vulnerability to stress and anxiety, we measured central activity of corticotropin-releasing factor (CRF) in patients with TS and the related condition, obsessive compulsive disorder (OCD). Lumbar cerebrospinal fluid (CSF) was obtained in a standardized fashion for measurement of CRF from 21 medication-free outpatients with TS, 20 with OCD, and 29 healthy controls. The TS patients had significantly higher levels of CSF CRF than both the normal controls and the OCD patients. However, there was no difference in CSF CRF between the OCD patients and the normal controls. Group differences in CSF CRF were unrelated to current clinical ratings of depression, anxiety, tics, and obsessive compulsive behaviors. Although the functional significance of this finding remains to be elucidated, these results are consistent with the hypothesis that stress-related neurobiological mechanisms may play a role in the pathobiology of TS.

Adolescent↗
PubMed1995

Amplitude and frequency modulation of pulsatile luteinizing hormone-releasing hormone release.

1. A variety of neuroendocrine approaches has been used to characterize cellular mechanisms governing luteinizing hormone-releasing hormone (LHRH) pulse generation. We review recent in vivo microdialysis, in vitro superfusion, and in situ hybridization experiments in which we tested the hypothesis that the amplitude and frequency of LHRH pulses are subject to independent regulation via distinct and identifiable cellular pathways. 2. Augmentation of LHRH pulse amplitude is proposed as a central feature of preovulatory LHRH surges. Three mechanisms are described which may contribute to this increase in LHRH pulse amplitude: (a) increased LHRH gene expression, (b) augmentation of facilitatory neurotransmission, and (c) increased responsiveness of LHRH neurons to afferent synaptic signals. Neuropeptide Y (NPY) is examined as a prototypical afferent transmitter regulating the generation of LHRH surges through the latter two mechanisms. 3. Retardation of LHRH pulse generator frequency is postulated to mediate negative feedback actions of gonadal hormones. Evidence supporting this hypothesis is reviewed, including results of in vivo monitoring experiments in which LHRH pulse frequency, but not amplitude, is shown to be increased following castration. A role for noradrenergic neurons as intervening targets of gonadal hormone negative feedback actions is discussed. 4. Future directions for study of the LHRH pulse generator are suggested.

Animals↗
PubMed1994

Enhanced stress responsivity of Tourette syndrome patients undergoing lumbar puncture.

Tourette's syndrome (TS) is a complex inherited neuropsychiatric disorder that is characterized by multiple motor and phonic tics. Stress-related fluctuations in symptom severity and medication responsiveness are common, and patients often report that tics are worsened by fatigue, emotional trauma, and anxiety. We examined the effects of lumbar puncture (LP) stress on plasma adrenocorticotropin (ACTH) and cortisol, urinary catecholamines, and self- and clinician ratings of anxiety in 13 medication-free TS patients and 10 normal controls, ages 17 to 41 years. The TS patients secreted significantly more ACTH than the normal controls in response to the stress of the lumbar puncture. Compared to the controls the TS patients had significantly greater postLP mean and postLP peak ACTH levels. The TS patients also excreted significantly more norepinephrine in the 20 hr preceding the lumbar puncture and reported higher levels of anxiety before and during the procedure than the controls. In addition, urinary norepinephrine excretion of the TS patients was significantly correlated with clinician ratings of tic severity. The results were not related to current levels of depression and anxiety. Taken together, these findings suggest that a subset of TS patients may be characterized by heightened reactivity of the hypothalamic-pituitary-adrenal axis and related noradrenergic sympathetic systems.

Adrenocorticotropic Hormone↗
PubMed1994

MR imaging of head and neck tumors: comparison of T1-weighted contrast-enhanced fat-suppressed images with conventional T2-weighted and fast spin-echo T2-weighted images.

OBJECTIVE: The purpose of this study was to determine the value of three MR pulse sequences for the detection of tumors and abnormal lymph nodes in the head and neck. This was accomplished by quantifying differences in contrast between tumor, lymph node, and respective adjacent tissue on contrast-enhanced fat-suppressed T1-weighted MR images, conventional spin-echo T2-weighted images, and fast spin-echo fat-suppressed T2-weighted images in a group of patients with head and neck tumors. SUBJECTS AND METHODS: Two groups of patients with head and neck tumors were studied. In the first group (16 patients), contrast-enhanced fat-suppressed T1-weighted images were compared with conventional spin-echo T2-weighted images. In the second group (21 patients), contrast-enhanced fat-suppressed T1-weighted images were compared with fast spin-echo fat-suppressed T2-weighted images. The detectability of tumor and abnormal lymph nodes was measured by calculating the contrast-to-noise ratio. RESULTS: The fat-suppressed T1-weighted images had significantly higher (p < or = .02) contrast-to-noise ratios for both the primary tumor and lymph nodes than either conventional or fast spin-echo T2-weighted images did. However, subjective evaluation of the contrast-to-noise ratios proved satisfactory for tumor detection with all three imaging sequences (contrast-enhanced fat-suppressed T1-weighted, fast spin-echo fat-suppressed T2-weighted, and conventional T2-weighted). CONCLUSION: Our results show that fat-suppressed contrast-enhanced T1-weighted images provide the highest contrast-to-noise ratio for head and neck tumors and abnormal lymph nodes. However, head and neck tumors encompass a broad range of neoplasms that are distributed in a complicated anatomic area. Therefore, in some patients, a combination of contrast-enhanced fat-suppressed T1- and T2-weighted images, preferably fast spin-echo fat-suppressed images, is useful for detection of these tumors and nodal metastases.

Carcinoma, Squamous Cell↗
PubMed1989

The corticotropin-releasing hormone test in patients with posttraumatic stress disorder.

To evaluate the hypothalamic-pituitary-adrenal (HPA) axis in patients with posttraumatic stress disorder (PTSD), we measured adrenocorticotropin hormone (ACTH) and cortisol responses following administration of corticotropin-releasing hormone (CRH) in 8 combat veterans with chronic PTSD. The PTSD patients had a significantly lower ACTH response to CRH compared to a control group of normal volunteers. Blunted ACTH responses occurred in patients with PTSD alone, as well as those PTSD patients who also had major depression. The cortisol response, although reduced, was not significantly different from normal. The blunted ACTH response to CRH in PTSD patients is similar to that seen in other psychiatric disorders, such as depression, panic disorder, and anorexia nervosa.

Adrenocorticotropic Hormone↗
PubMed1988

Elevated CSF dynorphin A [1-8] in Tourette's syndrome.

A recent neuropathological study has reported decreased levels of dynorphin A immunoreactivity in striato-pallidal fibers in the brain of a patient with severe Gilles de la Tourette's syndrome (TS). This observation, taken with the neuroanatomic distribution of dynorphin and its broad range of motor and behavioral effects, has led to speculation concerning its role in the pathobiology of TS. We report on the presence of elevated concentrations of dynorphin A [1-8] in the CSF of 7 TS patients, aged 20 to 45 years. The increase in CSF dynorphin was found to be associated with the severity of the obsessive compulsive symptoms but not with tic severity in these patients. Although CSF studies lack the precision necessary to address questions of selective involvement of neuronal system in specific CNS locations, these findings suggest that endogenous opioids are involved in the pathobiology of TS and related disorders. Tourette's syndrome (TS) is a chronic neuropsychiatric disorder of childhood onset that is characterized by multiple motor and phonic tics that wax and wane in severity and an array of behavioral problems including some forms of obsessive compulsive disorder (OCD) (1). Once thought to be a rare condition, the prevalence of TS is now estimated to be one case per 1,000 boys and one case per 10,000 girls, and milder variants of the syndrome are likely to occur in a sizeable percentage of the population (2). Although the etiology of TS remains unknown, the vertical transmission of TS within families follows a pattern consistent with an autosomal dominant form of inheritance (3,4). Neurobiologic and pharmacological data have implicated central monoaminergic and neuropeptidergic systems in the pathophysiology of TS, and basal ganglia structures remain the prime candidates as the neuroanatomical origin for TS and related conditions (1). Endogenous opioids, including dynorphin and met-enkephalin are concentrated in structures of the basal ganglia (5), are known to interact with central dopaminergic neurons (6, 7), and may play an important role in the control of motor functions (8). Post-mortem brain studies have directly implicated opioids in the pathophysiology of Parkinson's disease (9), Huntington's disease (10), and most recently in TS (11). The neuropathological study of Haber et al. (11) reported decreased levels of dynorphin A [1-17] immunoreactivity in striatal fibers projecting to the globus pallidus in the brain of a patient with severe TS. This ovservation, taken with the neuroanatomic distribution of dynorphin and its broad range of motor and behavioral effects, has led to speculation concerning its role in the pathobiology of TS.(ABSTRACT TRUNCATED AT 400 WORDS)

Dynorphins↗
PubMedDate not supplied

An integrated model for measuring management performance.

A model of organizational performance measurement that compels attention to the proper balance among quality, cost, and access; takes into account patient perceptions; produces clear targets for continual quality improvement (CQI); yields easily understood graphical displays; and captures health care organizations in simultaneous operation across the functions of cost, quality, and access was designed for the 22 medical treatment facilities of the Strategic Air Command. Such a tool provides practitioners, payers, and patients a range of information--from systemwide, facility, clinical service, and practitioner-specific insights on current performance to resource forecasts and easily understood targets for CQI. This case study shows that integrated performance modeling may be useful in examining many health management and reform issues.

Data Collection↗