bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypothalamic digoxin, hemispheric chemical dominance and sarcoidosis
Authors: Ravi Kumar A. , Kurup Parameswara Achutha 
Published: June 2004

Background/aims:The isoprenoid pathway produces three key metabolites: endogenous digoxin (membrane sodium-potassium ATPase inhibitor, immunomodulator and regulator of neurotransmitter/amino acid transport), dolichol (regulates N-glycosylation of proteins) and ubiquinone (free radical scavenger). The role of the isoprenoid pathway in the pathogenesis of sarcoidosis in relation to hemispheric dominance was studied.Methods:The isoprenoid pathway-related cascade was assessed in patients with systemic sarcoidosis with pulmonary involvement. The pathway was also assessed in patients with right hemispheric, left hemispheric and bihemispheric dominance for comparison to find out the role of hemispheric dominance in the pathogenesis of sarcoidosis.Results:In patients with sarcoidosis there was elevated digoxin synthesis, increased dolichol and glycoconjugate levels and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in the cholesterol:phospholipid ratio and a reduction in the glycoconjugate level of red blood cell (RBC) membrane in this group of patients. The same biochemical patterns were obtained in individuals with right hemispheric dominance. In individuals with left hemispheric dominance the patterns were reversed.Conclusions:Endogenous digoxin, by activating the calcineurin signal transduction pathway of T cells, can contribute to immune activation in sarcoidosis. An altered glycoconjugate metabolism can lead to the generation of endogenous self-glycoprotein antigens in the lung as well as other tissues. Increased free radical generation can also lead to immune activation. The role of a dysfunctional isoprenoid pathway and endogenous digoxin in the pathogenesis of sarcoidosis in relation to right hemispheric chemical dominance is discussed. All the patients with sarcoidosis were right-handed/left hemispheric dominant according to the dichotic listening test, but their biochemical patterns were suggestive of right hemispheric chemical dominance. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test.
Plasma concentrations of α‐MSH, AgRP and leptin in lean and obese men and their relationship to differing states of energy balance perturbation
Authors: Hoggard Nigel , Johnstone Alexandra M. , Faber Peter , Gibney Eileen R. , Elia Marinos , Lobley Gerald , Rayner Vernon , Horgan Graham , Hunter Leif , Bashir Shabina , Stubbs R. James 
Published: June 2004

Summaryobjective  A great deal of attention has focused on the central role of alpha melanocyte‐stimulating hormone (α‐MSH) and its antagonism at the melanocortin‐4 receptor (MC4R) by agouti related protein (AgRP) in the regulation of energy balance. However, very little is known regarding the function of circulating AgRP and α‐MSH in humans. We aimed to determine whether circulating α‐MSH and AgRP are responsive to long‐term perturbations in energy balance, in a manner consistent with their central putative functions.design and measurements  Circulating α‐MSH, AgRP and leptin were measured in both lean (n = 11) and obese (n = 18) male volunteers, some of whom (lean n = 11, obese n = 12) were then allocated one of two weight‐loss dietary strategies to achieve about 5% weight loss. This was achieved by either total starvation (for 4–6 days) for rapid weight loss or a very low calorie diet (VLCD, 2·6 MJ/day) (11–12 days) for less rapid weight loss, in both the lean and obese volunteers.results  At baseline, prior to any weight loss both plasma α‐MSH (15·8 ± 1·2 vs. 5·8 ± 1·0 pmol/l ± SEM; P < 0·001) and AgRP (49·4 ± 2·4 vs. 10·1 ± 0·9 pg/ml ± SEM; P < 0·001) were elevated in obese subjects compared with lean. In both cases this correlated closely with fat mass (P < 0·001), percentage body fat (P < 0·001) and leptin (P < 0·05). Plasma AgRP increased significantly during a 6‐day fast in lean individuals (11·1 ± 1·6 vs. 21·6 ± 3·1 pg/ml ± SEM; P < 0·05) but not in the VLCD subjects or in the obese, while α‐MSH was not affected by any changes in energy balance in either the lean or the obese volunteers.conclusion  We show a difference in α‐MSH and AgRP in lean and obese subjects that correlates closely with body fat at baseline. We demonstrate an increase in plasma AgRP during a 6‐day fast in lean individuals that is coincident with a decrease in plasma leptin. This increase in AgRP was not due to weight loss per se as there was no change in AgRP as a result of the same weight loss in the VLCD intervention in lean individuals. The source of the increase in plasma AgRP and its physiological function in the periphery remains to be elucidated but we suggest that the dynamics of the change in plasma leptin may determine the elevation in fasting plasma AgRP in lean subjects.
A longitudinal study of bone‐related biochemical changes at the menopause
Authors: Nordin B. E. Christopher , WIshart Judith M. , Clifton Peter M. , McArthur Rosemary , Scopacasa Franca , Need Allan G. , Morris Howard A. , O'Loughlin Peter D. , Horowitz Michael 
Published: June 2004

Summaryobjective  To evaluate the effects of the menopause on bone‐related biochemical variables in a longitudinal study.design  Recruitment by advertisement of premenopausal women over the age of 44 for measurement of selected variables and collection of blood and urine samples for deep freezing, followed by annual check of menopausal status and repeat collection of blood and urine samples for deep freezing after the menopausal transition.patients  A total of 104 women with confirmed premenopausal status and on no treatment likely to affect calcium or bone metabolism were admitted to the study over a period of 2 years. After 8 years, 43 of the volunteers had passed through the menopause and the study was closed.measurements  Radiocalcium absorption was measured at the first attendance and again after the menopausal transition. Calcium and other relevant variables were measured consecutively on paired thawed‐out samples of blood and urine.results  The data were complete in 34 subjects. In these women, there were highly significant correlations between the first and second measurements of most variables – serum calcium and fractions, radiocalcium absorption, vitamin D metabolites, PTH and others – indicating significant ‘tracking’ of these variables across the menopause. Within that framework there were significant rises in serum total and calculated ionized calcium (both P < 0·001) without change in mean serum parathyroid hormone (PTH). Radiocalcium absorption fell (P < 0·001) without change in serum 1,25D. There was a rise in fasting urinary calcium (P < 0·001) which could not be explained by the rise in filtered load and therefore represented a fall in TmCa (P < 0·001). There were significant rises in urinary bone resorption markers, pyridinoline and deoxypyridinoline (P < 0·001).conclusions  We conclude that the menopausal rise in calculated serum ionized calcium without fall in PTH, indicates a change in PTH set‐point, and that the falls in gastrointestinal absorption and renal tubular reabsorption of calcium reflect the loss of an oestrogen action at these two sites. Although these changes are sufficient to explain the rise in calcium requirement at the menopause, the association of high bone resorption with normal serum PTH suggests also an increased sensitivity of bone to the action of parathyroid hormone. There is significant ‘tracking’ of many variables across the menopause despite very significant changes in their absolute values.
Contribution of Ca2+‐Activated K+ Channels to Hyperpolarizing After‐Potentials and Discharge Pattern in Rat Supraoptic Neurones
Authors: Greffrath W. , Magerl W. , Disque‐Kaiser U. , Martin E. , Reuss S. , Boehmer G. 
Published: June 2004

AbstractThe contribution of Ca2+‐activated K+ channels to hyperpolarizing after‐potentials (HAP) of action potentials, to spike‐frequency adaptation and thus to the shaping of discharge pattern, was examined in rat supraoptic magnocellular neurosecretory cells. In addition, the expression of BK channels and SK3 subunits of SK channels was studied using double immunofluorescence detection. The presence of BK channels and SK3 subunits was detected in many supraoptic neurones containing either vasopressin or oxytocin. Current‐clamp recordings of current‐induced spike trains revealed that HAPs comprise a fast and a slow HAP (fHAP and sHAP). Correlation analyses revealed that the increase of the fHAP in amplitude and spike broadening were correlated to a moderate gradual increase of the interspike interval and thus to weak spike‐frequency adaptation. By contrast, marked prolongation of the interspike interval and strong spike‐frequency adaptation depended on the appearance and on the amplitude of the sHAP. The sHAP and spike‐frequency adaptation were blocked by cadmium, as well as by the SK channel antagonist apamin. The fHAP was attenuated by the BK channel antagonist iberiotoxin (IbTX), by the BK/IK channel antagonist charybdotoxin (ChTX) and by apamin. ChTX attenuated fHAPs throughout the entire spike train. By contrast, the IbTX‐induced attenuation of the fHAP was restricted to the initial part of the spike train, while the apamin‐induced attenuation slowly increased with the progression of the spike train. These results suggest that strong spike‐frequency adaptation in supraoptic neurones essentially depends on the generation of the sHAP by activation of SK channels. Comparison of effects of IbTX, ChTX and apamin suggests a complementary contribution of SK‐, BK‐ and IK‐channels to fHAPs.
Differential Effects of Repeated Restraint Stress on Pulsatile Lutenizing Hormone Secretion in Female Fischer, Lewis and Wistar Rats
Authors: Li X. F. , Edward J. , Mitchell J. C. , Shao B. , Bowes J. E. , Coen C. W. , Lightman S. L. , O'Byrne K. T. 
Published: June 2004

AbstractStress activates the hypothalamic‐pituitary‐adrenocortical (HPA) axis and can suppress pulsatile luteinizing hormone (LH) secretion, resulting in reproductive dysfunction. The histocompatible inbred Fischer and Lewis rat strains exhibit marked phenotypic differences in the activity of the HPA axis, the former being more reactive. Using Fischer, Lewis and Wistar rats, we assessed effects of repeated restraint stress on pulsatile LH secretion. Adult rats were ovariectomized and fitted with cardiac catheters. Blood samples were collected at 5‐min intervals for 3–5 h for detection of LH. Less frequent samples were collected for corticosterone measurement. After 2 h, rats were restrained for 60 min. The same regimen was repeated four times at 6‐day intervals. The mean peak corticosterone levels achieved during the first restraint in Fischer rats were significantly higher than those in Lewis and Wistar rats. By the time of the fourth episode of restraint, there had been some adaptation of the corticosterone response in the Fischer, but not in the Lewis or Wistar rats. LH pulses were interrupted during the 1st restraint in all experimental groups, although only Fischer rats showed suppression of LH pulses during the subsequent 2‐h postrestraint period. During the fourth restraint, LH pulse frequency was still reduced in Wistar, but not in Fischer and Lewis rats, both of which showed a complete habituation. These results suggest that differential control mechanisms underlie the response of the HPA and HPG axes to repeated restraint stress.
Antidepressants Blunt the Effects of Inescapable Stress on Male Mating Behaviour and Decrease Corticotropin‐Releasing Hormone mRNA Expression in the Hypothalamic Paraventricular Nucleus of the Syrian Hamster (Mesocricetus auratus)
Authors: Cordner A. P. , Herwood M. B. , Helmreich D. L. , Parfitt D. B. 
Published: June 2004

AbstractStress decreases sexual activity. However, emerging research suggests that the psychological aspect of control prevents the detrimental effects of stress on male mating behaviour. The present study examined the effects of chronic escapable/inescapable stress on mating behaviour in the male Syrian hamster. Additionally, the ability of the antidepressant clomipramine to prevent the adverse effects of stress on mating behaviour was explored. In this paradigm, two groups received the same electric footshock stress, but differed in the psychological aspect of control. Cohorts were divided into two groups. One group received clomipramine via a sugar water solution while the other received plain sugar water. Mating behaviour was quantified before and after 12 consecutive days of stress. The morning following the final stress and behaviour session, trunk blood and brains were collected to assess: (i) plasma concentrations of testosterone and glucocorticoids and (ii) corticotropin‐releasing hormone (CRH) mRNA expression within the paraventricular nucleus of the hypothalamus (PVN). In the drug‐free groups, several aspects of mating behaviour were disrupted by inescapable but not escapable stress, including anogenital investigation before the first ejaculation and time of first ejaculation. Additionally, both escapable and inescapable stress caused a decrease in total hit rate compared to the no‐stress control group. Unlike the sugar‐water treated animals, hamsters in either stress condition receiving clomipramine showed no differences in anogenital investigation, time of first ejaculation, hit rate, or any other aspect of mating behaviour measured, compared to the clomipramine no‐stress control males. The stress‐induced inhibition of mating behaviour could not be explained by changes in baseline plasma concentrations of testosterone or total glucocorticoids; these values did not vary between any of the six treatment groups. It was found that clomipramine lowers CRH mRNA expression in the PVN by 74%, regardless of stressor conditions. The results of the present study have broad implications for understanding the relationships between stress, depression and reproduction, and for the treatment of people and animals suffering from the adverse effects of stress.
Chorioamnionitis/funisitis and the development of bronchopulmonary dysplasia
Authors: Kent A , Dahlstrom JE 
Published: June 2004

Objective:  To examine the association between chorioamnionitis with or without funisitis and bronchopulmonary dysplasia in infants less than 30 completed weeks gestation given the current standards of antenatal steroid and surfactant use.Methods:  Infants included in the study were those delivered at less than 30 completed weeks gestation from January 1996 to July 2001, identified from a prospectively managed database. Placental pathology was reviewed for the presence or absence of chorioamnionitis and funisitis. Infants were divided into three groups depending on degree of exposure to fetal inflammation (no inflammation, chorioamnionitis only and chorioamnionitis and funisitis). Data relating to gestational age, sex, antenatal steroid exposure, surfactant treatment, days of positive pressure ventilation and days of oxygen required were collected. Bronchopulmonary dysplasia was defined as death due to respiratory failure or any oxygen requirement at 36 weeks postmenstrual age.Results:  Two hundred and forty‐one infants were included in the study. The mean gestational age was 27.7 weeks and mean birthweight 1089 g. One hundred and sixty‐one infants were not exposed to any in utero inflammation, 40 showed chorioamnionitis and 40 showed chorioamnionitis and funisitis. There was no significant difference between antenatal steroid and surfactant treatment between the three groups. There was no significant difference between the three groups in the development of bronchopulmonary dysplasia. Low gestational age was the most significant predictor of developing bronchopulmonary dysplasia.Conclusion:  The risk of developing bronchopulmonary dysplasia is not increased following exposure to chorioamnionitis or funisitis in the context of current antenatal steroid and surfactant use. The most significant predictor for developing bronchopulmonary dysplasia is gestational age at the time of delivery.
Prospective cohort study of definite spider bites in Australian children
Authors: Isbister GK 
Published: June 2004

Objectives:  To describe the clinical effects of spider bites in a paediatric population and compare to bites in an adult population.Methods:  Prospective follow up study of children with definite spider bites where the spiders were immediately collected and expertly identified. Cases were recruited from Australian emergency departments and poison information centres and followed up. Data were collected on circumstances of bites and clinical effects, and compared with similar data from adult spider bites.Results:  There were 163 cases (62% male, 38% female; age <16, median age 7 years, interquartile range (IQR): 3−11 years). The median duration of effects was 2 h (IQR 0.25−12 h). The commonest spiders were Huntsman spiders (Sparassidae) and Orb weavers (Araneidae), and comparatively few bites by theridiid spiders, including Red‐back spiders. Pain or discomfort occurred in all bites and was severe in 20%. Local effects included puncture marks/bleeding (36%) and red mark/redness (73%). Systemic effects occurred in only 6% of cases. There were no necrotic lesions or ulcers as a consequence of any spider bites (0%; 97.5% CI 0.0−2.2%) and no early allergic reactions or secondary infections. The median duration of clinical effects was shorter than adults, the frequency of severe pain was less than adults and systemic effects were less common in children.Conclusions:  Paediatric spider bite causes minor effects in the majority of cases, and is unlikely to cause necrotic ulcers, allergic reactions or infection. The severity and duration of effects differ from adults.
Arterial ischaemic stroke in children
Authors: Barnes C , Newall F , Furmedge J , Mackay M , Monagle P 
Published: June 2004

Objective:  Arterial ischaemic stroke (AIS) in childhood is a serious disorder about which little is published. The aim of this study is to determine the epidemiology and outcome of AIS in Australian children.Methods:  Cases of childhood AIS occurring at the Royal Children's Hospital, Melbourne 1993−2001, were identified by medical record search using International Classification of Disease Codes. Information was collected on demographics, risk factors, arterial distribution, results of thrombophilic testing, management and outcome.Results:  During the 8 years of review 95 patients presented with 98 cases of AIS calculating an incidence of 1.8 per 100 000 children per year. Children less than 12 months of age represented greater than one third of all cases. Identifiable risk factors were present in 64% of cases with congenital heart disease the major risk factor. Thrombophilic testing was incomplete with initial abnormalities present in 18% of cases tested. The estimated stroke‐related mortality was 8.4%. Of the patients who survived and who had follow‐up details available, 78% had a neurological deficit. Twenty‐six patients (26%) received anticoagulation. There was no statistically significant association between treatment with anticoagulation and normal neurological outcome.Conclusion:  AIS is over‐represented in children under 12 months of age and results in death or residual neurological impairment in the majority of cases. Further prospective studies are needed to identify risk factors for poor outcome. The recently established Australian and New Zealand Stroke and Thrombophilia Registry should provide important information on clinical and laboratory based risk factors and create a basis for international clinical trials to improve the outcome of childhood AIS.
Restorative proctocolectomy in patients with ulcerative colitis having a recto‐vaginal fistula
Authors: Zinicola R. , Nicholls R. J. 
Published: June 2004

AbstractObjective  Recto‐vaginal fistula is a rare complication of ulcerative colitis. There are few reports of restorative proctocolectomy carried out in patients with ulcerative colitis having a rectovaginal fistula. We report our experience with this condition.Patients and methods  Between 1 January 1976 and 31 December 2001, 838 patients underwent restorative proctocolectomy for ulcerative colitis at one hospital. These included 400 women of whom 4 (1%) had an already present rectovaginal fistula. We reviewed all patients who presented with a rectovaginal fistula. These patients were contacted by telephone to establish function and satisfaction.Results  The mean age was 30.0 years (range 19–39 years). The mean age at onset of ulcerative colitis was 21.5 years (range 13–34 years). One patient was asymptomatic, the fistula being discovered at operation. In the other three patients the recto‐vaginal fistula had occurred at a mean of 108 months (range 72–192 months) after the onset of ulcerative colitis. Three of four patients had had previous episodes of acute severe disease. Three patients had a narrow rectum with deep ulceration. The mean distance between the anorectal junction and the site of fistulation was 2.7 cm (range 0–7 cm). Three patients had a three‐stage and one patient a two‐stage procedure. Mean follow‐up after closure of the loop ileostomy was 107 months (range17–276 months). All patients were treated successfully but 2 (50%) had a recurrence at 156 and 40 months after the closure of the loop ileostomy. One patient was diverted and the fistula was closed by a subsequent transanal repair and the other patient was treated with success by temporary loose seton technique. Two patients had excellent functional results whereas two other had some difficulties in continence. Nevertheless all patients were satisfied with the outcome.Conclusions  Patients with ulcerative colitis and a recto‐vaginal fistula can be successfully treated by restorative proctocolectomy, nevertheless they are at risk of late recurrence of the fistula.
Completion rate to caecum as a quality measure of colonoscopy in a district general hospital
Authors: Gorard D. A. , McIntyre A. S. 
Published: June 2004

AbstractObjective  Published colonoscopy completion rates vary substantially and audits suggest they often fall short of the 85% completion rate to caecum considered acceptable by some authorities. We audited colonoscopy completion rates in our unit and aimed to investigate reasons for failure.Methods  We analysed all colonoscopies, including those by trainees, performed in a district general hospital over a 16‐month period. Reasons for failure to complete were investigated and alterations to working practices made where necessary.Results  The unit had an 89.1% completion rate overall (95% CI 87–92%) with rates varying from 75% to 97% for individuals. Colorectal carcinomas were detected in 3.9% of all colonoscopies of which 17% occurred proximal to the caecum and 16% in the ascending colon. Working practices in those endoscopists felt not to be meeting targets were altered and a re‐audit confirmed a trend towards improvement in those individuals. Using these data we also identified a definite learning curve in trainees, with at least 40 procedures required to meet the target of 85% completion rate to caecum.Conclusion  In a District General Hospital high standards of colonoscopy can be achieved. Reasons for failure to complete colonoscopy to the caecum are many and often they are beyond the control of the colonoscopist (e.g. poor preparation, obstructing lesion). Colonoscopy to the caecum is not always necessary and is not a good measure of the quantity of colonic mucosa visualized. We have reservations with regard to using this target alone as a measure of quality.