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Biomedical subjects

M S Smith

Publications and source records attributed to M S Smith.

At least 37 records · Page 2Linked to original sources

Corticotropin releasing hormone neurons in the paraventricular nucleus are direct targets for neuropeptide Y neurons in the arcuate nucleus: an anterograde tracing study.

In the present study, anterograde tracing combined with triple label immunofluorescent staining was conducted to examine the possible anatomical interactions between Neuropeptide Y (NPY) neurons in the arcuate nucleus of the hypothalamus (ARH) and the corticotropin releasing hormone (CRH) system in the paraventricular nucleus of the hypothalamus (PVH). The anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L), was iontophresed into the ARH of female rats and triple label immunofluorescence staining with three different fluorophores was performed to visualize PHA-L, NPY and CRH, with the aid of confocal microscopy. In PVH, NPY and PHA-L double-labeled fibers were found mainly in the parvocellular part of the PVH (PVHp). Confocal analysis demonstrated that NPY/PHA-L double-labeled fibers came in close apposition to CRH perikarya. In the median eminence, NPY/PHA-L double-labeled fibers were found both in the inner and the outer zones of the median eminence. However, very few double-labeled fibers were found in the proximity of CRH neuronal fibers in the median eminence. Double label staining was also performed to determine if NPY Y1 receptors were expressed in CRH neurons. Two different fluorophores were used to visualize CRH neurons and Y1 receptor. No convincing Y1-positive staining was found in CRH cell bodies in the PVH, even though Y1-positive staining in numerous fibers and cell bodies was observed throughout the region. However, Y1-positive fibers were shown to make close contact with CRH cell bodies in the PVH. In the ME, the majority of the Y1-positive fibers were located in the lateral portion of the ME, whereas the CRH fibers were found mainly in the medial portion of the external zone of the ME. The results of the present study suggest that ARH NPY neurons provide direct input into CRH cell bodies in the PVH region. However, the direct effects of NPY must be mediated by some receptor subtype other than Y1. Y1 receptor involvement in NPY modulation of CRH neuronal function in the PVH appears to be indirect through modulation of neuronal afferents making contact with CRH neurons.

Animals↗

The effects in humans of rapid loss of body mass on a boxing-related task.

The physiological effects of strategies for a rapid loss of body mass immediately before weighing-in for competition in weight-governed sports are unclear. This study examined the effects of a 3%-4% loss in body mass on a boxing-related task. Seven novice amateur boxers completed three 3 min rounds of simulated boxing on a prototype boxing ergometer in an euhydrated state (E-trial) and after exercise-induced thermal dehydration (D-trial). All subjects lost body mass following dehydration-mean body mass fell 3.8 (SD +/- 0.3)% [77.3 (SD +/- 11.3) to 74.4 (SD +/- 10.7) kg, P<0.001] - but changes in plasma volume (PV) were inconsistent. Four subjects suffered reductions in PV between 15% and 30%, one subject maintained his E-trial value and two recorded an increase. The D-trial mean PV value was 8.0 (SD +/- 17.2)% lower but this fall was not statistically significant (P>0.05). Analysis of D-trial boxing performance showed one subject maintained his performance over the two trials and a second improved 17.8%. A two-way ANOVA (condition x time) with repeated measures on both factors showed no significant main effect differences for condition (F1,6 = 3.93 P>0.05), time (F1.83,48 = 1.12, P>0.05) or interaction between them (F1.93,48, P>0.05). Furthermore, neither heart rate nor blood lactate responses in the boxing task differed between trials. These data were affected by the small sample. Power and effect size analysis using eta(2) procedure and removing the outlier data produced a mean fall in boxing performance of 26.8%. However, some subjects appeared able to resist the deleterious effects of a rapid loss of body mass prior to competition and further research is needed to explain the mechanisms under-pinning this ability.

Adult↗

Emergency medicine can play a leadership role in enterprise-wide clinical information systems.

At many institutions, the department of emergency medicine is uniquely suited to a leadership role in the deployment of new clinical decision support systems (computer systems that support clinical practice). Many factors favor such a leadership role, including institutional politics, organizational structure, extent of local control, clinician solidarity, openness to change, departmental size and scale, and willingness to take risks. Such a role should be undertaken in partnership with the institution's information services (IS) department, and a clear understanding of goals and responsibilities will facilitate such a partnership. A leadership position with respect to new information systems entails a certain risk, but the potential benefit to an emergency department in today's competitive environment is substantial. The authors' experience with one such collaborative development project is presented.

Computers↗

Neuropeptide Y Y5 receptor protein in the cortical/limbic system and brainstem of the rat: expression on gamma-aminobutyric acid and corticotropin-releasing hormone neurons.

Neuropeptide Y displays diverse modes of action in the CNS including the modulation of cortical/limbic function. Some of these physiological actions have been at least partially attributed to actions of neuropeptide Y on the Y5 receptor subtype. We utilized an antibody raised against the Y5 receptor to characterize the distribution of this receptor subtype in the rat cortical/limbic system and brainstem. Y5-like immunoreactivity was located primarily in neuronal cell bodies and proximal dendritic processes throughout the brain. In the cortex, Y5 immunoreactivity was limited to a subpopulation of small gamma-aminobutyric-acid interneurons (approximately 15 microm diameter) scattered throughout all cortical levels. Double label immunofluorescence was also used to demonstrate that all of the Y5 immunoreactive neurons in the cortex displayed intense corticotropin releasing hormone immunoreactivity. The most intense Y5 immunoreactive staining in the hippocampus was located in the pyramidal cell layer of the small CA2 subregion and the fasciola cinerea, with lower levels of staining in the hilar region of the dentate gyrus and CA3 subregion of the pyramidal cell layer. Nearly all of the Y5 immunoreactive neurons in the hilar region of the hippocampus displayed gamma-aminobutyric-acid immunoreactivity. In the brainstem, Y5 immunoreactivity was most intense in the Edinger-Westphal nucleus, locus coeruleus and the mesencephalic trigeminal nucleus. The present study provides neuroanatomical evidence for the possible sites of action of the neuropeptide Y/Y5 receptor system in the control of cortical/limbic function. The presence of Y5 immunoreactivity on cell bodies and proximal dendritic processes in specific regions of the hippocampus suggests that this receptor functions to modulate postsynaptic activity. These data also suggest that the neuropeptide Y/Y5 system may play a role in the modulation of a specific population of GABAergic neurons in the cortex, namely those that contain corticotropin-releasing hormone. The location of the Y5 receptor immunoreactivity fits with the known physiological actions of neuropeptide Y and this receptor.

Animals↗

Sleep quality and presleep arousal in chronic pain.

This study was designed (1) to characterize the extent and nature of sleep complaints of chronic pain patients and (2) to examine the factors that predict sleep quality. A heterogeneous sample of 51 outpatients with benign, chronic pain was recruited from newspaper and pain clinic advertisements. Patients completed a variety of self-report instruments including the Multidimensional Pain Inventory, the Pittsburgh Sleep Quality Index, the Pre-Sleep Arousal Scale, and the Beck Depression Inventory. Sleep complaints were reported by 88% of the sample. Presleep cognitive arousal, rather than pain severity, was found to be the primary predictor of sleep quality.

Adolescent↗

Sensorineural hearing loss in ulcerative colitis.

Sensorineural hearing loss has been described in a small number of patients with ulcerative colitis. At present, it is not known whether this is a rare and sporadic association, or whether these reports represent an under recognised extra-intestinal manifestation of ulcerative colitis. The aim of this study was to determine the prevalence of hearing loss in patients with ulcerative colitis. Twenty patients with active ulcerative colitis (mean age 45 years) were recruited prospectively along with 20 healthy age- and sex-matched controls. Otoscopy, tympanometry and pure tone audiometry were performed. The activity of the disease was scored according to a 12-month cumulative disease activity index. No patients complained of auditory symptoms. Otoscopy and tympanometry were normal in all patients and controls. Pure tone audiometry showed significant sensorineural hearing loss over all frequencies in patients with ulcerative colitis compared with controls. This preliminary study indicates that subclinical sensorineural hearing loss is associated with ulcerative colitis. Further study is warranted to determine the nature of the relationship and its pathological basis.

Adult↗

Differential regulation of leptin receptor but not orexin in the hypothalamus of the lactating rat.

During lactation, hypothalamic levels of neuropeptide Y (NPY) and agouti related protein (AGRP) mRNA are increased, while pro-opiomelanocortin (POMC) mRNA is decreased. Serum leptin levels are also decreased during lactation. These changes may underlie the large increases of both food and water intake that occur in concert with milk production. However, additional hypothalamic substances, such as the novel peptide, orexin, may be involved. In addition, in the presence of chronically suppressed levels of serum leptin, there may be a change in leptin receptor expression in the hypothalamus. The objectives of the present study were to determine if orexin and leptin receptor mRNA levels were changed during lactation. Rats were studied on dioestrus of the oestrous cycle or on day 10 postpartum (the lactating animals were suckling eight pups). Orexin mRNA levels in the lateral hypothalamus did not differ between dioestrus and lactation. There was a significant increase in leptin receptor mRNA levels in the supraoptic nucleus during lactation compared to dioestrus. Furthermore, leptin receptor protein, as determined by immunocytochemistry, was colocalized in virtually all vasopressin and oxytocin cells in the supraoptic nucleus. Lactating animals exhibited a decrease in leptin receptor mRNA in the ventromedial hypothalamic nucleus whereas no change was apparent in other hypothalamic areas compared to the dioestrus animals. These results demonstrate that changes in orexin do not appear to contribute to the increase in food intake during lactation. It is likely that the increases in NPY and ARGP, coupled with the decrease in POMC, are primarily responsible for sustaining the chronic hyperphagia of lactation. The changes observed in leptin receptor expression in the hypothalamus, along with the suppression of serum leptin levels, also suggest that the leptin signalling system may play a significant role in the regulation of food and water intake during lactation.

Agouti-Related Protein↗

Duodenal perforation by a Wallstent.

Endoscopic and/or radiological insertion of metallic mesh stents has recently been described as an alternative to palliative bypass operation in patients with gastric outlet obstruction caused by advanced malignant disease. We report a complication caused by migration and late perforation of the duodenum by a Wallstent, which raised concerns about the place of this procedure as an alternative to surgical bypass. The Wallstents have sharp ends and could cause ulcers or perforation of the viscus. Modification of the current Wallstent design may be needed.

Aged↗

Development of a boxing dynamometer and its punch force discrimination efficacy.

The development of sport-specific dynamometers is an important step towards ecological validity in analysing athlete performance. Design limitations in previous punch-measuring devices have resulted in values which may not or cannot fully reflect the force and multidirectional components in a punch. In developing this boxing dynamometer, a triaxial force measurement system and a boxing manikin interface were combined. The repeatability and accuracy of the dynamomoter were assessed using simulated straight punches. Discrimination efficacy was assessed by comparison of the maximal punching force of seven elite, eight intermediate and eight novice boxers during simulated boxing, throwing straight punches. For the elite, intermediate and novice groups, respectively, the maximal straight punching forces (mean +/- s(mean)) were 4800 +/- 227 N, 3722 +/- 133 N and 2381 +/- 116 N for the rear hand, and 2847 +/- 225 N, 2283 +/- 126 N and 1604 +/- 97 N for the lead hand. For all groups, maximal forces were larger for the rear than the lead hand (P < 0.001). Maximal punching force was greater in the elite than the intermediate group, and greater in the intermediate than the novice group (P < 0.05). The boxing dynamometer discriminated effectively between punching performance at three standards of performance and between the punching force of the rear and lead hands.

Biomechanical Phenomena↗

Lipopolysaccharide-induced biliary factors enhance invasion of Salmonella enteritidis in a rat model.

In this study, the role of the hepatobiliary system in the early pathogenesis of Salmonella enteritidis infection was investigated in a rat model. Intravenous (i.v.) challenge with lipopolysaccharide (LPS) has previously been shown to enhance the translocation of normal gut flora. We first confirmed that LPS can similarly promote the invasion of S. enteritidis. Oral infection of outbred Australian Albino Wistar rats with 10(6) to 10(7) CFU of S. enteritidis led to widespread tissue invasion after days. If animals were similarly challenged after intravenous administration of S. enteritidis LPS (3 to 900 microg/kg of body weight), significant invasion of the livers and mesenteric lymph nodes (MLN) occurred within 24 h, with invasion of the liver increasing in a dose-dependent fashion (P < 0.01). If bile was prevented from reaching the intestine by bile duct ligation or cannulation, bacterial invasion of the liver and MLN was almost totally abrogated (P < 0.001). As i.v. challenge with LPS could induce the delivery of inflammatory mediators into the bile, biliary tumor necrosis factor alpha (TNF-alpha) concentrations were measured by bioassay. Biliary concentrations of TNF-alpha rose shortly after LPS challenge, peaked with a mean concentration of 27.0 ng/ml at around 1 h postchallenge, and returned to baseline levels (3.1 ng/ml) after 2.5 h. Although TNF-alpha cannot be directly implicated in the invasion process, we conclude that the invasiveness of the enteric pathogen S. enteritidis is enhanced by the presence of LPS in the blood and that this enhanced invasion is at least in part a consequence of the delivery of inflammatory mediators to the gastrointestinal tract by the hepatobiliary system.

Animals↗

Alterations in basal glucose metabolism during late pregnancy in the conscious dog.

We assessed basal glucose metabolism in 16 female nonpregnant (NP) and 16 late-pregnant (P) conscious, 18-h-fasted dogs that had catheters inserted into the hepatic and portal veins and femoral artery approximately 17 days before the experiment. Pregnancy resulted in lower arterial plasma insulin (11 +/- 1 and 4 +/- 1 microU/ml in NP and P, respectively, P < 0.05), but plasma glucose (5.9 +/- 0.1 and 5.6 +/- 0.1 mg/dl in NP and P, respectively) and glucagon (39 +/- 3 and 36 +/- 2 pg/ml in NP and P, respectively) were not different. Net hepatic glucose output was greater in pregnancy (42.1 +/- 3.1 and 56.7 +/- 4.0 micromol. 100 g liver(-1).min(-1) in NP and P, respectively, P < 0.05). Total net hepatic gluconeogenic substrate uptake (lactate, alanine, glycerol, and amino acids), a close estimate of the gluconeogenic rate, was not different between the groups (20.6 +/- 2.8 and 21.2 +/- 1.8 micromol. 100 g liver(-1). min(-1) in NP and P, respectively), indicating that the increment in net hepatic glucose output resulted from an increase in the contribution of glycogenolytically derived glucose. However, total glycogenolysis was not altered in pregnancy. Ketogenesis was enhanced nearly threefold by pregnancy (6.9 +/- 1.2 and 18.2 +/- 3.4 micromol. 100 g liver(-1).min(-1) in NP and P, respectively), despite equivalent net hepatic nonesterified fatty acid uptake. Thus late pregnancy in the dog is not accompanied by changes in the absolute rates of gluconeogenesis or glycogenolysis. Rather, repartitioning of the glucose released from glycogen is responsible for the increase in hepatic glucose production.

3-Hydroxybutyric Acid↗

Identification of neuronal input to the arcuate nucleus (ARH) activated during lactation: implications in the activation of neuropeptide Y neurons.

Activation of the neuropeptide Y (NPY) neuronal system in the arcuate nucleus of the hypothalamus (ARH) during lactation in the rat is likely due to the neural impulses arising from the suckling stimulus. However, the afferent neuronal input to the ARH that is activated during lactation and is responsible for activation of NPY neurons is currently unknown. Previously, using cFos as a marker for neuronal activation, we identified several brain areas in the lactating animals that were activated by the suckling stimulus. Thus, the objective of the present study was to determine if these activated areas observed in the lactating animals project directly into the ARH. The retrograde tracer, fluorogold (FG), was injected into the ARH on day 4 postpartum. Chronically suckled rats were then deprived of their eight-pup litters on day 9 postpartum, and 48 h later, the pups were returned to the females to reinitiate the suckling stimulus for 90 min to induce cFos expression. The animals were then perfused and the brains were subjected to double-label immunohistochemistry to visualize both FG- and cFos-positive cells. Substantial FG/cFos double-labeled cells were found in forebrain regions, including the medial preoptic area, periventricular preoptic area, bed nucleus of the stria terminalis, and the medial amygdala, and in brainstem regions including the lateral parabrachial nucleus, peripeduncular area and ventrolateral medulla. The results of the present study demonstrate that specific areas in the brain are activated during lactation and send direct projections to the ARH. Thus, these areas are potentially important candidates for mediating the activation of the NPY neuronal system in the ARH during lactation.

Animals↗

Alpha1-adrenergic receptors in human spinal cord: specific localized expression of mRNA encoding alpha1-adrenergic receptor subtypes at four distinct levels.

alpha1-Adrenergic receptors (alpha1ARs) are important in lower urinary tract syndromes such as benign prostatic hypertrophy and bladder irritability. Spinal cord alpha1ARs have been postulated to play a role in modulating these diseases, yet alpha1AR subtype (alpha1a, alpha1b, alpha1d) neuronal localization in human spinal cord has not been described. We therefore tested the hypothesis that alpha1AR subtype distribution varies according to specific spinal cord tract and level. In situ hybridization was performed to identify cell bodies containing alpha1AR subtype mRNA at four levels of human spinal cord (cervical enlargement, thoracic, lumbar, sacral). alpha1AR mRNA is present in ventral gray matter only (ventral>dorsal; sacral>lumbar=thoracic>cervical). Signaling cell bodies were detected in anterior horn motor neurons at all levels; dorsal nucleus of Clarke and intermediolateral columns in cervical enlargement, thoracic and lumbar spinal cord regions; and parasympathetic nucleus in sacral spinal cord. Although all three alpha1AR subtypes are present throughout human spinal cord, alpha1d mRNA predominates overall. If confirmed at a protein level, these findings may contribute to the development of new therapeutic strategies in the treatment of several human diseases.

Humans↗

Congenital smooth muscle hamartoma of the conjunctival fornix.

PURPOSE: Congenital smooth muscle hamartomas are benign tumors composed of proliferating smooth muscle cells. They are usually seen as abnormal patches of skin. Ocular involvement of congenital smooth muscle hamartomas is unusual, with rare reports of patients with external eyelid involvement or proptosis resulting from orbital tumors. We describe a patient with a congenital smooth muscle hamartoma that involved the tarsal conjunctival fornix. METHODS: Review of the patient's medical records, including the results of ophthalmologic, radiologic, and histologic examinations. RESULTS: A healthy 2-year-old boy was initially seen with a conjunctival mass. He had a discrete, gray, cystic-appearing lesion in the inferior fornix of the left eye. A magnetic resonance imaging study revealed no signs of extension of the lesion into the orbit. The lesion was surgically excised. Histologic sections showed large bundles of smooth muscle with a fibrotic background and interdigitating fat, consistent with a diagnosis of a congenital smooth muscle hamartoma. CONCLUSION: To our knowledge, this is the first report of a patient with a congenital smooth muscle hamartoma arising from the conjunctival fornix. It presumably originated from either the smooth muscle of the vascular endothelium or from the capsulopapebral muscle. Congenital smooth muscle hamartoma should be considered in the differential diagnosis of cystic-appearing conjunctival fornix lesions.

Child, Preschool↗

Neural populations in the rat forebrain and brainstem activated by the suckling stimulus as demonstrated by cFos expression.

During lactation in the rat, the suckling stimulus plays an important role in mediating alterations in hypothalamic neuroendocrine function associated with lactation. To provide the basis for understanding the neural circuitry that may transmit suckling-induced signals into the hypothalamus, the present study used the expression of the immediate-early gene product, cFos protein, as a marker for neuronal activation to identify neural populations in the brain of lactating female rats activated by the suckling stimulus. In addition, cFos expression induced by the exteroceptive sensory stimuli (olfactory, auditory, visual) associated with pup exposure alone was also determined. Thus, cFos patterns in response to the physical suckling stimulus, which would include exteroceptive sensory stimuli associated with pup exposure, were compared with the patterns induced in response to pup exposure alone, so that neuronal populations specifically activated by the suckling stimulus could be identified. After 90 min of suckling, several forebrain areas, including the lateral septum, medial preoptic area, periventricular preoptic area and supraoptic nucleus of hypothalamus, showed a significant increase in cFos expression, compared with non-suckled controls and pup exposure animals. In addition, in the bed nucleus of stria terminalis, the medial amygdala and several cortical areas, cFos-positive cells were found in both suckling and pup exposure animals. In the brainstem, the suckling stimulus induced a significant increase in cFos expression in the ventrolateral medulla, locus coeruleus, lateral parabrachial nucleus, lateral and ventrolateral portions of the caudal part of the periaqueductal gray, and caudal portion of the paralemniscal nucleus, compared with non-suckled controls and pup exposure animals. As expected, in several areas related with sensory input, such as reticular formation and pontine nucleus, cFos expression was found in both suckling and pup exposure animals. Moreover, when double-label immunocytochemistry was used to identify cFos- and catecholamine-positive neurons in the brainstem, it was found that catecholamine-positive neurons in the ventrolateral medulla and locus coeruleus showed a significant increase in cFos expression in response to suckling compared with non-resuckled and pup-exposure groups. Using cFos expression as a marker for neuronal activation, the present studies identified the neural populations in the brain that are activated by the suckling stimulus. By comparing the pattern of cFos expression observed in response to pup exposure alone or the suckling stimulus, the present studies differentiated the neural populations activated by the physical suckling stimulus from the populations activated by the exteroceptive sensory stimuli associated with pup exposure. These suckling-activated areas are likely candidates for playing an important role in transmitting the effects of the suckling stimulus into the hypothalamus to regulate neuroendocrine alterations associated with lactation.

Animals↗

Recurrent headache in adolescents: nonreferred versus clinic population.

OBJECTIVE: To compare headache activity, psychosocial measures, and cold pressor response between referred and nonreferred adolescents with frequent headache. DESIGN: Thirteen boys and 19 girls with a mean age of 13.4 +/- 0.9 years who had been referred to a hospital-based behavioral treatment program for recurrent headache were compared with an age- and sex-matched school-based population of nonreferred students consisting of 31 adolescents with frequent headaches and 32 adolescents with infrequent or no headaches. All subjects completed the Spielberger State-Trait Anxiety Inventory/Trait form, the Children's Depression Inventory, the Childhood Somatization Inventory, and measures of headache activity and related functional disability. Additionally, all subjects reported interval discomfort scores on a 40-second cold pressor test with arm immersion in a 10 degrees +/- 1 degree C cold water bath. RESULTS: Subjects from both headache groups reported significantly more anxiety than those with infrequent or no headaches. The school-based nonreferred adolescents reported more depressive symptoms than the clinic-based referred subjects. In addition, the latter group reported headaches of longer duration and more school days missed due to headaches than both other groups. Whereas school-based subjects and those with infrequent or no headaches reported relatively low initial cold pressor test scores and gradually reported increasing scores with time, clinic-based subjects rated their discomfort as high at the initial interval report and maintained high levels throughout the test. No differences in somatization were found among groups. CONCLUSION: Although adolescents who seek behavioral treatment for recurrent headache do not report more psychological symptoms than nonreferred adolescents with frequent headaches, they report headaches of longer duration, miss more school days due to headache, and report higher initial sustained discomfort scores to a standardized noxious stimulus.

Adaptation, Psychological↗