Crohn's disease with oral presenting signs masquerading as chronic osteomyelitis

Background: A case of Crohn's disease (CD) was diagnosed following recognition of oral and systemic signs and symptoms in a 19-year-old male patient. Methods: Clinical investigation utilized included blood tests (full blood count, electrolytes, urea, creatinine, liver function tests), computed tomogrphy scans, magnetic resonance imaging scans, oral biopsies, colonoscopy and biopsies of the terminal ileum and colon. Results: A diagnosis of CD was made which then allowed appropriate medical treatment to be initiated. Conclusion: The importance of a thorough medical history and full physical examination with appropriate investigations as dictated by clinical findings is demonstrated.

Photosynthetic responses of the coral Montipora digitata to cold temperature stress

Coral bleaching events have become more frequent and widespread, largely due to elevated sea surface temperatures. Global climate change could lead to increased variability of sea surface temperatures, through influences on climate systems, e.g. El Nino Southern Oscillation (ENSO). Field observations in 1999, following a strong ENSO, revealed that corals bleached in winter after unusually cold weather. To explore the basis for these observations, the photosynthetic responses of the coral species Montipora digitata Studer were investigated in a series of temperature and light experiments. Small replicate coral colonies were exposed to ecologically relevant lower temperatures for varying durations and under light regimes that ranged from darkness to full sunlight. Photosynthetic efficiency was analyzed using a pulse amplitude modulated (PAM) fluorometer (F-0, F-m, F-v/F-m), and chlorophyll a (chl a) content and symbiotic dinoflagellate density were analyzed with spectrophotometry and microscopy, respectively. Cold temperature stress had a negative impact on M digitata colonies indicated by decreased photosynthetic efficiency (F-v/F-m), loss of symbiotic dinoflagellates and changes in photosynthetic pigment concentrations. Corals in higher light regimes were more susceptible to cold temperature stress, Moderate cold stress resulted in photoacclimatory responses, but severe cold stress resulted in photodamage, bleaching and increased mortality. Responses to cold temperature stress of M digitata appeared similar to that observed in corals exposed to warmer than normal temperatures, suggesting a common mechanism. The results of this study suggest that corals and coral reefs may also be impacted by exposure to cold as well as warm temperature extremes as climate change occurs.

Myoelectric manifestations of sternocleidomastoid and anterior scalene muscle fatigue in chronic neck pain patients

Objective: This study compares myoelectric manifestations of fatigue of the sternocleidomastoid (SCM) and anterior scalene (AS) muscles between 10 chronic neck pain subjects and 10 normal matched controls. Methods: Surface electromyography (sEMG) signals were recorded from the sternal bead of SCM and AS muscles bilaterally during submaximal isometric cervical flexion contractions at 25 and 50% of the maximum voluntary contraction (MVC). The mean frequency, average rectified value and conduction velocity of the sEMG signal were calculated to quantify myoelectric manifestations of muscle fatigue. Results: For both the SCM and AS muscles, the Mann-Whitney U test indicated that the initial value and slope of the mean frequency in neck pain patients were greater than in healthy subjects (P < 0.05). This was significant both at 25 and 50% of MVC. Conclusions: These results suggest: (a) a predominance of type-II fibres in the neck pain patients and/or (b) greater fatigability of the superficial cervical flexors in neck pain patients. These results are in agreement with previous muscle biopsy studies in subjects with neck pain, which identified transformation of slow-twitch type-I fibres to fast-twitch type-IIB fibres, as well as the clinical observation of reduced endurance in the cervical flexors in neck pain patients. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Core outcome domains for chronic pain clinical trials: IMMPACT recommendations

Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. Methods. Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia. governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain. Conclusions. There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy. (C) 2003 International Association for the Study of Pain.

Induction of metallothionein in human skin by routine exposure to sunlight: Evidence for a systemic response and enhanced induction at certain body sites

Expression of metallothionein, an antioxidant induced by a variety of stimuli including ultraviolet light, was quantitated by immunohistochemistry in the skin of males aged over 50 who had known short- and long-term exposures to sunlight. Skin punch biopsies were taken from two sites in each subject: the hand in all subjects and a range of other sites matched to patients with a previously excised primary melanoma. Metallothionein expression (strongest in the basal layers of the epidermis and primarily nuclear) was associated with both short- and long-term exposure to sunlight. A plateau of staining intensity was reached after 3 h sun exposure, within the previous 3 d before biopsy. Expression was also elevated in the nonexposed skin sites of subjects who had recent sun exposure, indicating a systemic response to exposure of remote sites. Using the skin of the hand to normalize responses to chronic exposure between individuals, the systemically modulated response to sunlight was significantly greater on the unexposed back than on other sites. The possibility of ultraviolet-induced cytokines selectively modifying the response of skin on a site-specific basis was investigated. The circulating leukocytes, but not lymphocytes, of two individuals exposed to 1 minimal erythema dose whole-body solar-simulated ultraviolet showed increased interleukin-6 mRNA 4 h after exposure. Interleukin-6 was not directly induced in these cell populations 4 h after ultraviolet A or ultraviolet B irradiation ex vivo . Leukocytes may therefore contribute to and amplify the systemic effects of ultraviolet-induced interleukin-6 and metallothionein expression.

Perceived stress as a predictor of the self-reported new diagnosis of symptomatic CHD in older women

This article describes one aspect of a prospective cohort study of 10,432 women aged between 70 and 75 years. After a 3-year period, 503 women self-reported a new diagnosis by a doctor of angina or myocardial infarction (symptomatic coronary heart disease [CHD]). Time one psychosocial variables (Duke Social Support Index, time pressure, Perceived Stress Scale, Mental Health Index, having a partner, educational attainment, and location of residence) were analyzed using univariate binary logistic regression for their ability to predict subsequent symptomatic CHD. Of these variables, the Duke Social Support Index, Perceived Stress Scale and the Mental Health Index were found to be significant predictors of symptomatic CHID diagnosis. Only the Perceived Stress Scale, however, proved to be a significant independent predictor. After controlling for time one nonpsychosocial variables, as well as the frequency of family doctor visits, perceived stress remained a significant predictor of the new diagnosis of symptomatic CHD in this cohort of older women over a 3-year period.

Oxidative stress is responsible for deficient survival and dendritogenesis in Purkinje neurons from ataxia-telangiectasia mutated mutant mice

Atm gene-disrupted mice recapitulate the majority of characteristics observed in patients with the genetic disorder ataxia-telangiectasia (A-T). However, although they exhibit defects in neuromotor function and a distinct neurological phenotype, they do not show the progressive neurodegeneration seen in human patients, but there is evidence that ataxia-telangiectasia mutated ( Atm)-deficient animals have elevated levels of oxidized macromolecules and some neuropathology. We report here that in vitro survival of cerebellar Purkinje cells from both Atm knock-out and Atm knock-in mice was significantly reduced compared with their wild-type littermates. Although most of the Purkinje neurons from wild-type mice exhibited extensive dendritic elongation and branching under these conditions, most neurons from Atm-deficient mice had dramatically reduced dendritic branching. An antioxidant ( isoindoline nitroxide) prevented Purkinje cell death in Atm-deficient mice and enhanced dendritogenesis to wild-type levels. Furthermore, administration of the antioxidant throughout pregnancy had a small enhancing effect on Purkinje neuron survival in Atm gene-disrupted animals and protected against oxidative stress in older animals. These data provide strong evidence for a defect in the cerebellum of Atm-deficient mice and suggest that oxidative stress contributes to this phenotype.

Effects of glucose-insulin-potassium infusion on chronic ischaemic left ventricular dysfunction

Background: Glucose-insulin-potassium (GIK) infusion improves cardiac function and outcome during acute ischaemia. Objective: To determine whether GIK infusion benefits patients with chronic ischaemic left ventricular dysfunction, and if so whether this is related to the presence and nature of viable myocardium. Methods: 30 patients with chronic ischaemic left ventricular dysfunction had dobutamine echocardiography and were given a four hour infusion of GIK. Segmental responses were quantified by improvement in wall motion score index (WMSI) and peak systolic velocity using tissue Doppler. Global responses were assessed by left ventricular volume and ejection fraction, measured using a three dimensional reconstruction. Myocardial perfusion was determined in 15 patients using contrast echocardiography. Results: WMSI (mean (SD)) improved with dobutamine (from 1.8 (0.4) to 1.6 (0.4), p < 0.001) and with GIK (from 1.8 (0.4) to 1.7 (0.4) p < 0.001); there was a similar increment for both. Improvement in wall motion score with GIK was observed in 55% of the 62 segments classed as viable by dobutamine echocardiography, and in 5% of 162 classed as non-viable. There was an increment in peak systolic velocity after both doputamine echocardiography (from 2.5 (1.8) to 3.2 (2.2) cm/s, p < 0.01) and GIK (from 3.0 (1.6) to 3.5 (17) cm/s, p < 0.001). The GlK effects were not mediated by changes in pulse, mean arterial pressure, lactate, or catecholamines, nor did they correlate with myocardial perfusion. End systolic volume improved after GlK (p = 0.03), but only in 25 patients who had viable myocardium on dobutom ne echocardiography. Conclusions: In patients with viable myocardium and chronic left ventricular dysfunction, GlK improves wall motion score, myocardial velocity, and end systolic volume, independent of effects on haemodynamics or catecholamines. The response to GlK is observed in areas of normal and abnormal perfusion assessed by contrast echocardiography.

Evidence for a sub-morphological inflammatory process in the liver in haemochromatosis

Background/Aims: The role of cytokines in hepatic injury has been examined for many liver diseases however little is known of the cytokine involvement in haemochromatosis. The aim of the current study was to examine the hepatic gene expression of potential proinflammatory and profibrogenic cytokines in haemochromatosis. Methods: Interferon-gamma, interleukin-10, transforming growth factor-beta(1) and tumor necrosis factor-alpha mRNA expression was assessed in liver tissue from 20 haemochromatosis patients, eight controls and eight chronic hepatitis C patients. To assess the immunophenotype of the inflammatory infiltrate in haemochromatosis, liver sections were subjected to immunohistochemistry using markers for macrophages (CD68, HAM56, MAC387) or T cells (CD3 and CD45RO). Results: Interferon-gamma mRNA was increased in both haemochromatosis (0.29+/-0.08%, P=0.01) and hepatitis C patients (1.02+/-0.32%, P=0.03) compared to controls (0.04+/-0.01%). Interleukin-10 mRNA was significantly decreased in both haemochromatosis and hepatitis C patients (0.01+/-0.003%, P=0.008 and 0.03+/-0.015%, P=0.02, respectively) compared to controls (0.12+/-0.01%). CD3 positive T-cell number was significantly correlated with increasing hepatic iron concentration (r=0.56, P=0.03). Conclusions: This study has demonstrated a distinct pattern of cytokine gene expression in haemochromatosis, which resembles that of inflammatory conditions such as chronic hepatitis C. These factors may play a role in the development of iron-induced hepatic fibrosis in haemochromatosis. (C) 2003 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.

Independent contribution of plaque complexity to myocardial ischemia during Dobutamine stress echocardiography

The influence of complex plaque morphology on the extent of demand-induced ischemia in unselected patients is not well defined. We sought to investigate the functional significance of lesion morphology in patients who underwent coronary angiography and dobutamine stress echocardiography (DSE).,Angiography and DSE were performed within a 6-month period (mean 1 +/- 1 month) in 196 patients. Angiographic assessments involved quantification of stenosis severity, assessment of the extent of jeopardized myocardium, and categorization of plaque morphology according to the Ambrose classification. DSE was interpreted by separate investigators with respect to wall motion score index (WMSI) and number of coronary territories involved. A general linear model was constructed to assess,the independent contribution of patient characteristics and angiographic and DSE results with respect to extent of ischemic myocardium. Complex lesion morphology was seen in 62 patients (32%). Patients with complex lesions were more likely to have had prior myocardial infarction (p < 0.001) and be current smokers (p = 0.03). During angiography, they exhibited a trend toward a greater number of diseased vessels, had a greater coronary jeopardy score (p < 0.001) and more frequent collateral flow (p = 0.03). During echocardiography, patients had a higher stress WMSI (p < 0.001) and were more likely to show ischemia in all 3 arterial territories (p < 0.01). On multivariate regression, the coronary artery jeopardy score and the presence of complex plaque morphology were independent predictors of the extent of ischemic myocardium (R 2 = 34%, p < 0.001). Thus, patients with complex plaque morphology are older, more likely to smoke, and more likely to have had prior myocardial. infarction. They exhibit more extensive disease with higher coronary jeopardy scores and a higher resting and peak stress WMSI. Despite these differences, complex plaque morphology remains an independent predictor of the extent of ischemia during stress. (C) 2003 by Excerpta Medica, Inc.

In overweight patients with chronic hepatitis C, circulating insulin is associated with hepatic fibrosis: implications for therapy

Background/Aims: Host factors such as increased body mass index (BMI) and genotype-specific viral factors contribute to the development of steatosis in patients with chronic hepatitis C (HCV). We hypothesized that host metabolic factors associated with increased BMI may play a role in disease progression. Methods: Fasting serum was collected from 160 patients with chronic HCV at the time of liver biopsy and 45 age, gender and BMI matched controls, and assessed for levels of insulin, c-peptide and leptin. Results: Patients with viral genotype 3 had more severe steatosis (P = 0.0001) and developed stages 1 and 2 fibrosis at a younger age (P < 0.05) than patients with genotype 1. For both genotypes, overweight patients had significantly more steatosis and increased insulin and leptin levels. In contrast to lean patients, there was a statistically significant increase in circulating insulin levels with increasing fibrosis in overweight patients with chronic HCV (P = 0.03). Following multivariate analysis, insulin was independently associated with fibrosis (P = 0.046) but not inflammation (P = 0.83). There was no association between serum leptin levels and stage of fibrosis. Conclusions: Increasing circulating insulin levels may be a factor responsible for the association between BMI and fibrosis in patients with HCV, irrespective of viral genotype. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A Sco homologue plays a role in defence against oxidative stress in pathogenic Neisseria

Sco proteins are found in mitochondria and in a variety of oxidase positive bacteria. Although Sco is required for the formation of the Cu-A centre in a cytochrome oxidase of the aa(3) type, it was observed that oxidases with a Cu-A centre are not present in many bacteria that contain a Sco homologue. Two bacteria of this type are the pathogens Neisseria meningitidis and Neisseria gonorrhoeae. The sco genes of N. gonorrhoeae strain 1291 and N. meningitidis strain MC58 were cloned, inactivated by inserting a kanamycin resistance cassette and used to make knockout mutants by allelic exchange. Both N. gonorrhoeae and N. meningitidis sco mutants were highly sensitive to oxidative killing by paraquat, indicating that Sco is involved in protection against oxidative stress in these bacteria. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

Method for determining the shear stress in cylindrical systems

We develop a method for determining the elements of the pressure tensor at a radius r in a cylindrically symmetric system, analogous to the so-called method of planes used in planar systems [B. D. Todd, Denis J. Evans, and Peter J. Daivis, Phys. Rev. E 52, 1627 (1995)]. We demonstrate its application in determining the radial shear stress dependence during molecular dynamics simulations of the forced flow of methane in cylindrical silica mesopores. Such expressions are useful for the examination of constitutive relations in the context of transport in confined systems.