Macrophage collections in gastrointestinal biopsies and metabolic disorders: two unusual case reports.
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Adolescent↗
Biomedical subjects
S Francis
Publications and source records attributed to S Francis.
Representations of pleasant and painful touch in the human orbitofrontal and cingulate cortices.
The cortical areas that represent affectively positive and negative aspects of touch were investigated using functional magnetic resonance imaging (fMRI) by comparing activations produced by pleasant touch, painful touch produced by a stylus, and neutral touch, to the left hand. It was found that regions of the orbitofrontal cortex were activated more by pleasant touch and by painful stimuli than by neutral touch and that different areas of the orbitofrontal cortex were activated by the pleasant and painful touches. The orbitofrontal cortex activation was related to the affective aspects of the touch, in that the somatosensory cortex (SI) was less activated by the pleasant and painful stimuli than by the neutral stimuli. This dissociation was highly significant for both the pleasant touch (P < 0.006) and for the painful stimulus (P < 0.02). Further, it was found that a rostral part of the anterior cingulate cortex was activated by the pleasant stimulus and that a more posterior and dorsal part was activated by the painful stimulus. Regions of the somatosensory cortex, including SI and part of SII in the mid-insula, were activated more by the neutral touch than by the pleasant and painful stimuli. Part of the posterior insula was activated only in the pain condition and different parts of the brainstem, including the central grey, were activated in the pain, pleasant and neutral touch conditions. The results provide evidence that different areas of the human orbitofrontal cortex are involved in representing both pleasant touch and pain, and that dissociable parts of the cingulate cortex are involved in representing pleasant touch and pain.
Adult↗
Trial of heparin in viper bites.
AIMS OF THE STUDY: Viper bites produce hematotoxicity and coagulopathy which may be either true disseminated intravascular coagulation (DIC) or DIC-like syndrome. Role of heparin is studied in the present study of viper bite cases as use of heparin provides a rational therapy for defibrination caused by viper envenomation. METHODOLOGY: One hundred and twenty two patients with viper bite and incoagulable blood were randomised into test group and control group. Test group received heparin in addition to antisnake venom (ASV). Efficacy was assessed by monitoring bleeding time (BT), clotting time (CT), prothrombin time (PT), platelets, fibrinogen, blood urea (BU), serum creatinine, development of complications and overall outcome. RESULTS: Heparin group showed favourable outcome in all parameters studied. But many of them were not statistically significant. CONCLUSION: Heparin seems to be having a beneficial role which needs to be confirmed by larger trials and longer duration of heparin administration.
Adult↗
Complete airway obstruction in a ventilated patient after oesophageal dilatation.
A case of instrumental perforation of the oesophagus is presented. This caused systemic sepsis, requiring tracheal intubation and positive pressure ventilation. Sudden unexpected life-threatening airway obstruction was caused by distal tracheal compression by a peritracheal abscess. The aetiology and management of distal tracheal obstruction is discussed.
Aged↗
Single-shot T2(*) measurement to establish optimum echo time for fMRI: studies of the visual, motor, and auditory cortices at 3.0 T.
The signal change in fMRI is dependent on the echo time and the rate of decay of transverse magnetization. The latter factor may vary across regions of the brain as a result of variations in field homogeneity. Previous measurements of the signal change with echo time have generally employed relatively slow multi-echo techniques, which may be sensitive to movement and habituation effects. Here a fast T(2)(*) measurement technique, involving the generation of six low-resolution echo planar images from a single FID, is described, and its use in the evaluation of the optimum echo time for visual, motor, and auditory fMRI experiments at 3.0 T is outlined.
Auditory Cortex↗
Buscopan for the treatment of pain after laparoscopic sterilisation.
We investigated the effect of Buscopan 20 mg, given at the end of surgery, on analgesic requirements in 44 ASA I and II patients presenting as day cases for laparoscopic sterilisation using Filshie clips. Patients were randomly allocated to receive either intravenous Buscopan 20 mg or saline placebo at the end of surgery. There was no significant difference in pain scores, analgesic requirements or the incidence of nausea and vomiting between the two groups. We conclude that intravenous Buscopan 20 mg was not effective for pain relief following laparoscopic sterilisation.
Adult↗
Methylphenidate selectively improves story retelling in children with attention deficit hyperactivity disorder.
OBJECTIVES: The goal of this study was to determine stimulant effects on story grammar, comprehension, and errors in the narratives of children with attention deficit hyperactivity disorder (ADHD) with and without comorbid language impairment. Previous research has demonstrated impairments in the narrative abilities of children with ADHD, but the effect of the primary treatment modality (methylphenidate) is unknown. METHODS: Fifty children with ADHD (7 to 12 years of age) were stratified for language impairment that might influence performance. In an acute, randomized, placebo-controlled crossover trial with two single doses (10 and 20 mg) of methylphenidate, the children listened to an audiotaped story while viewing a wordless picture book of the study, then retold the story and answered comprehension questions. The narratives were transcribed and coded for story grammar, length, and errors. RESULTS: Methylphenidate only increased children's reporting of the story characters' internal responses and attempts. It had no effect on story length or responses to comprehension questions. Responses to the factual questions were significantly more accurate than the inferential questions, irrespective of medication dose. Comorbid language impairment had no effect on performance or stimulant response. CONCLUSION: Story grammar analysis was sensitive to drug effects, which were subtle but specific and clinically meaningful. Results provide evidence for the theoretical linkage between internal responses and attempts.
Attention Deficit Disorder with Hyperactivity↗
Perioperative morbidity of acoustic neuroma surgery.
OBJECTIVE: To review complications that occur during the course of acoustic neuroma surgery. STUDY DESIGN: Database and retrospective case review. SETTING: Tertiary referral center, private neurotologic practice. PATIENTS: A series of 1,687 patients undergoing acoustic neuroma surgery between 1987 and 1997. The 822 male and 865 female patients ranged in age from 10 to 87 years (mean age at time of surgery, 50 yr; standard deviation, 14 yr). The most common surgical approach was translabyrinthine (72.5%), followed by middle fossa (25.7%). The tumors ranged in size from 3 to 7 cm in diameter (mean, 2.0 cm; SD, 1.1 cm). MAIN OUTCOME MEASURE: Frequency of occurrence of all surgical and medical complications. RESULTS: The most common complications were cerebrospinal fluid leaks (9.4%; 2.1% requiring reoperation) and meningitis (1.5%). Other surgical complications included cerebral edema, hydrocephalus, pneumocephalus, lower cranial nerve dysfunction, and wound infection. Medical complications in order of frequency included cystitis, sacral root syndrome, anemia, and pneumonia/bronchitis. Complications were related to tumor size and diagnosis of neurofibromatosis type 2. CONCLUSIONS: Perioperative complications will occur with acoustic neuroma surgery, but the overall rate in this large series was low. The authors believe that this supports an aggressive treatment approach for management of acoustic tumors. The findings of this study provide a basis for comparison with other treatment approaches and also are useful for preoperative patient counseling.
Adolescent↗
The leucine zipper motif of the envelope glycoprotein ectodomain of human immunodeficiency virus type 1 contains conformationally flexible regions as revealed by NMR and circular dichroism studies in different media.
A 43-mer peptide derived from the coiled coil domain of the transmembrane glycoprotein, gp41, of human immunodeficiency virus type 1, was synthesized. Light scattering measurements suggested that the peptide molecules likely exist in the aqueous solution in trimeric form. Circular dichroism experiments showed a moderate helix population enhancement for the peptide in 80% methanol solution relative to helicity in sodium dodecyl sulfate micellar suspension. NMR spectroscopy indicated that the N-terminal section of the peptide was conformationally more sensitive to the medium. The conformationally labile regions contain residues implicated in gp41-gp120 association. Our data support the idea that the coiled coil region is responsible for oligomerization of the gp41 ectodomain and suggest a site of conformational isomerization following receptor binding-induced gp120 dissociation from gp41.
Amino Acid Sequence↗
Representation of pleasant and aversive taste in the human brain.
In this study, the representation of taste in the orbitofrontal cortex was investigated to determine whether or not a pleasant and an aversive taste have distinct or overlapping representations in this region. The pleasant stimulus used was sweet taste (1 M glucose), and the unpleasant stimulus was salt taste (0.1 M NaCl). We used an ON/OFF block design in a 3T fMRI scanner with a tasteless solution delivered in the OFF period to control for somatosensory or swallowing-related effects. It was found that parts of the orbitofrontal cortex were activated (P < 0.005 corrected) by glucose (in 6/7 subjects) and by salt (in 6/7 subjects). In the group analysis, separate areas of the orbitofrontal cortex were found to be activated by pleasant and aversive tastes. The involvement of the amygdala in the representation of pleasant as well as aversive tastes was also investigated. The amygdala was activated (region of interest analysis, P < 0.025 corrected) by the pleasant taste of glucose (5/7 subjects) as well as by the aversive taste of salt (4/7 subjects). Activation by both stimuli was also found in the frontal opercular/insular (primary) taste cortex. We conclude that the orbitofrontal cortex is involved in processing tastes that have both positive and negative affective valence and that different areas of the orbitofrontal cortex may be activated by pleasant and unpleasant tastes. We also conclude that the amygdala is activated not only by an affectively unpleasant taste, but also by a taste that is affectively pleasant, thus providing evidence that the amygdala is involved in effects produced by positively affective as well as by negatively affective stimuli.
Amygdala↗
Rab3B regulates ZO-1 targeting and actin organization in PC12 neuroendocrine cells.
Rab3B is a monomeric GTPase that modulates norepinephrine secretion when expressed in PC12 neuroendocrine cells. In the present study we determined whether rab3B also regulates the organization of intercellular junctions, since this GTPase localizes to regions of cell contact in multiple cell types. The stable expression of rab3B, but not the closely related rab3A, led to two morphological phenotypes in PC12 cells: (i) reorganization of F-actin into long filopodia and (ii) redistribution of the junction-associated protein ZO-1. ZO-1 localization was not appreciably affected by the expression of a GTP binding mutant of rab3B (N135I) that stimulates norepinephrine secretion by PC12 cells. The apparent diversity of these rab3B phenotypes implies that this GTPase is capable of influencing cell signaling pathways that in turn modulate the cytoskeleton and junction organization. In support of this hypothesis we observed that rab3B expression also altered the profile of proteins that interact with the signaling molecule, phosphatidylinositol 3-kinase (PI3-kinase). The effect of rab3B on protein interactions with PI3-kinase was reversed by inhibitors of this kinase. Furthermore, PI3-kinase inhibitors virtually abolished ZO-1 localization at the surfaces of cells that express rab3B, but not rab3A, whereas these inhibitors had no effect on rab3B-dependent norepinephrine secretion. Our results indicate that rab3B can influence junctional protein targeting and secretion by distinct mechanisms.
Actins↗
Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex.
When a food is eaten to satiety, its reward value decreases. This decrease is usually greater for the food eaten to satiety than for other foods, an effect termed sensory-specific satiety. In an fMRI investigation it was shown that for a region of the orbitofrontal cortex the activation produced by the odour of the food eaten to satiety decreased, whereas there was no similar decrease for the odour of a food not eaten in the meal. This effect was shown both by a voxel-wise SPM contrast (p <0.05 corrected) and an ANOVA performed on the mean percentage change in BOLD signal in the identified clusters of voxels (p <0.006). These results show that activation of a region of the human orbitofrontal cortex is related to olfactory sensory-specific satiety.
Eating↗
Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex.
When a food is eaten to satiety, its reward value decreases. This decrease is usually greater for the food eaten to satiety than for other foods, an effect termed sensory-specific satiety. In an fMRI investigation it was shown that for a region of the orbitofrontal cortex the activation produced by the odour of the food eaten to satiety decreased, whereas there was no similar decrease for the odour of a food not eaten in the meal. This effect was shown both by a voxel-wise SPM contrast (p<0.05 corrected) and an ANOVA performed on the mean percentage change in BOLD signal in the identified clusters of voxels (p<0.006). These results show that activation of a region of the human orbitofrontal cortex is related to olfactory sensory-specific satiety.
Brain Mapping↗
Fusion induced aggregation of model vesicles studied by dynamic and static light scattering.
Membrane fusion is a key step in the virus mediated cell fusion. The vesicular dispersion serves as a model system to study the membrane fusion. We employed dynamic and static light scattering to study the fusion of phosphatidylcholine vesicles in the presence of model fusion peptide fragments from the hemagglutinin HA2 protein. The fusion-induced aggregation under the present experimental setup exhibited strong pH dependence, similar to the parental viral protein. Replacement of the glycine residue at the extreme amino terminus by glutamic acid (G1E) abolished fusion activity. The average molecular mass and diameter of vesicular dispersion obtained from static and dynamic light scattering measurements respectively at neutral and acidic pH showed about three fold increase in acidic solution containing wild type fusion peptide. The light scattering data are consistent with lipid mixing results. The present work demonstrates the utility of light scattering as a facile means to monitor the fusion process.
Amino Acid Sequence↗
Interleukin-1 receptor antagonist expression in human endothelial cells and atherosclerosis.
The proinflammatory cytokine interleukin (IL)-1 is expressed mainly within the endothelium of atherosclerotic plaques and may be linked with inflammatory mechanisms of atherogenesis. IL-1 action is complex and regulated in part by its naturally occurring inhibitor, the IL-1 receptor antagonist (IL-1ra). Therefore, we studied differential and specific isoform expression of IL-1ra in the endothelium of diseased coronary arteries and in endothelial cells (ECs) stimulated under defined conditions. In view of an association with IL-1ra gene (IL-1RN) polymorphism, the influence of endothelial cell genotype at IL-1RN on IL-1ra protein production was also examined. Secreted IL-1ra and intracellular IL-1ra mRNAs were detected by semiquantitative reverse transcription-polymerase chain reaction in human atherosclerotic and dilated cardiomyopathic coronary arteries; protein expression appeared increased in atherosclerotic compared with dilated cardiomyopathic arteries, where IL-1ra appeared to be confined to the endothelium. Only intracellular IL-1ra type I mRNA was detected in human umbilical vein ECs (HUVECs) and human coronary artery ECs (HCAECs) when they were stimulated with bacterial lipopolysaccharide/phorbol myristate acetate and transforming growth factor-beta. IL-1beta and IL-1alpha were without effect. IL-1ra protein was detected in HUVECs (intracellular IL-1ra), HCAECs (intracellular IL-1ra), and human coronary artery smooth muscle cells (intracellular IL-1ra) by immunoprecipitation and Western blot. IL-1ra was detected in HUVEC cell lysates by ELISA and appeared to be influenced by the genotype of the IL-1RN variable number tandem repeat, an 86-bp repeat polymorphism in intron 2 of the IL-1ra gene, with lower levels of IL-1ra produced by IL-1RN allele 2-containing cells (ratio of IL-1ra to total protein: for 1,1 homozygotes, 1.38+/-0.28x10(-9) [n=15]; for 1,2 heterozygotes, 0.81+/-0.17x10(-9) [n=8]; and for 2,2 homozygotes, 0.63+/-0.19x10(-9) [n=5]; P<0.05 compared with 1,1 homozygotes). This is the first demonstration of IL-1ra in human diseased arteries, stimulated HUVECs, and HCAECs and indicates the endothelial cell as an important source. Endothelial IL-1ra production may be controlled by the endothelial IL-1RN genotype. These data further support the role of the IL-1 system of cytokines in the pathogenesis of atherosclerosis.
Arteriosclerosis↗
The representation of pleasant touch in the brain and its relationship with taste and olfactory areas.
Although there has been much investigation of brain pathways involved in pain, little is known about the brain mechanisms involved in processing somatosensory stimuli which feel pleasant. Employing fMRI it was shown that pleasant touch to the hand with velvet produced stronger activation of the orbitofrontal cortex than affectively neutral touch of the hand with wood. In contrast, the affectively neutral but more intense touch produced more activation of the primary somatosensory cortex than the pleasant stimulus. This indicates that part of the orbitofrontal cortex is concerned with representing the positively affective aspects of somatosensory stimuli, and in further experiments it was shown that this orbitofrontal area is different from that activated by taste and smell. The finding that three different primary or unlearned types of reinforcer (touch, taste, and smell) are represented in the orbitofrontal cortex helps to provide a firm foundation for understanding the neural basis of emotions, which can be understood in terms of states elicited by stimuli which are rewarding or punishing.
Brain↗
Temporal and spatial distribution of interleukin-1 beta in balloon injured porcine coronary arteries.
OBJECTIVE: Interleukin-1 beta (IL-1 beta) is a proinflammatory cytokine with a wide range of biological activities. We determined the distribution of IL-1 beta following percutaneous transluminal coronary angioplasty (PTCA) of porcine arteries, and the presence of caspase-1 (required for the activation of IL-1 beta). METHODS: Oversized balloon angioplasty was performed in Yorkshire White pigs and the vessels excised at selected intervals (1, 6, 18 h, 3, 7, and 14 days) post-PTCA. IL-1 beta and caspase-1 were then identified using reverse transcription polymerase chain reaction (RT-PCR), in situ RT-PCR, and immunohistochemistry. RESULTS: IL-1 beta protein was detected in the inflammatory infiltrate up to 3 days after PTCA. Luminal endothelial cells contained IL-1 beta at 1 h, with peak expression at 3-7 days. Adventitial capillaries were IL-1 beta-positive at all timepoints. IL-1 beta was detected in adventitial cells at 3 days, with reduced levels at 7 and 14 days. At 7 days, neointimal cells were also IL-1 beta positive. No IL-1 beta was detected in non-PTCA control arteries. RT-PCR demonstrated IL-1 beta mRNA expression to be induced at 1 h, and absent at 3 days. In situ RT-PCR revealed this expression to be distributed throughout the arterial layers at 6 h, but localized to the adventitia at 18 h, with a baseline expression in the adventitial layer of non-PTCA controls. Caspase-1 was detected in luminal endothelial cells from 6 h, in adventitial cells from 3 days, and in neointimal cells from 7 days post-PTCA. This expression colocalized with IL-1 beta, indicating the potential for the IL-1 beta present to become activated. CONCLUSIONS: We conclude that IL-1 beta is synthesised, in conjunction with caspase-1, by endothelial, inflammatory, and adventitial cells early (within 3 days) after PTCA, with decreased levels at later timepoints, suggesting that it has a key role to play in the early stages of healing following PTCA.
Angioplasty, Balloon, Coronary↗
A novel Bayesian decision procedure for early-phase dose-finding studies.
Phase I first-in-man studies in normal, healthy volunteers are performed to define a maximum safe dose and to identify a range of acceptable doses for later drug development studies in patients. Analysis of pharmacokinetic and pharmacodynamic data using mixed-effects modeling can be used to fit an overall dose-response relationship. By expressing prior information as pseudodata, the same methodology can be used to perform a Bayesian analysis and to determine posterior modal estimates for the model parameters. Decision theory can then be applied to maximize a chosen gain function, utilizing real-time data capture for choosing safe doses in a way that will provide more informative responses, thus accelerating study completion. The methodology is introduced elsewhere (1). The purpose of this paper is to describe software currently in development and to illustrate the method using an example from a recent study.
Area Under Curve↗