bluuebunny/crossref_metadata_2025_split huggingface dataset:
The opioid system in the gastrointestinal tract
Authors: Sternini C. , Patierno S. , Selmer I. ‐S. , Kirchgessner A. 
Published: September 2004

Abstractµ‐, δ‐ and κ‐opioid receptors (ORs) mediate the effects of endogenous opioids and opiate drugs. Here we report (1) the distribution of µOR in the guinea‐pig and human gastrointestinal tract in relation to endogenous ligands, to functionally distinct structures in the gut and to δOR and κOR; and (2) the ligand‐induced µOR endocytosis in enteric neurones using in vitro and in vivo models. In the guinea pig, µOR immunoreactivity is confined mainly to the myenteric plexus. µOR myenteric neurones are most numerous in the small intestine, followed by the stomach and the proximal colon. µOR immunoreactive fibres are dense in the muscle layer and the deep muscular plexus, where they are in close association with interstitial cells of Cajal. This distribution closely matches the pattern of enkephalin. µOR enteric neurones comprise functionally distinct populations of neurones of the ascending and descending pathways of the peristaltic reflex. In human gut, µOR immunoreactivity is localized to myenteric and submucosal neurones and to immune cells of the lamina propria. δOR immunoreactivity is located in both plexuses where it is predominantly in varicose fibres in the plexuses, muscle and mucosa, whereas κOR immunoreactivity appears to be confined to the myenteric plexus and to bundles of fibres in the muscle. µOR undergoes endocytosis in a concentration‐dependent manner, in vitro and in vivo. Pronounced µOR endocytosis is observed in neurones from animals that underwent abdominal surgery that has been shown to induce delay in gastrointestinal transit. We can conclude that all three ORs are localized to the enteric nervous system with differences among species, and that µOR endocytosis can be utilized as a means to visualize enteric neurones activated by opioids and sites of opioid release.
Preclinical studies of opioids and opioid antagonists on gastrointestinal function
Authors: Greenwood‐Van Meerveld B. , Gardner C. J. , Little P. J. , Hicks G. A. , Dehaven‐Hudkins D. L. 
Published: September 2004

AbstractOpioid receptors in the gastrointestinal (GI) tract mediate the effects of endogenous opioid peptides and exogenously administered opioid analgesics, on a variety of physiological functions associated with motility, secretion and visceral pain. The studies reviewed or reported here describe a range of in vivo activities of opioid receptor antagonists upon GI function in rodents, focusing on µ receptors. Naloxone, and the peripherally acting µ‐opioid receptor antagonists alvimopan and methylnaltrexone, reverse morphine‐induced inhibition of GI transit in mice and rats, and morphine‐ or loperamide‐induced inhibition of castor oil‐induced diarrhoea in mice. At doses producing maximal reversal of morphine‐induced effects upon GI transit, only the central nervous system (CNS) penetrant antagonist naloxone was able to reverse morphine‐induced analgesia. Both central and peripheral opioid antagonists may affect GI function and/or visceromotor sensitivity in the absence of exogenous opioid analgesics, suggesting a constitutive role for endogenous opioid peptides in the control of GI physiology. Furthermore, in contrast to naloxone, alvimopan does not produce hypersensitivity to the visceromotor response induced by nociceptive levels of colorectal distension in a rodent model of postinflammatory colonic hypersensitivity, suggesting that in the periphery endogenous μ‐opioid receptor‐mediated mechanisms do not regulate colonic sensitivity. The data support the hypothesis that peripherally acting opioid antagonists may be able to selectively block opioid receptors in the GI tract, thereby preserving normal GI physiology, while not blocking the effects of endogenous opioid peptides or exogenous opioid analgesics in the CNS. These findings suggest that the primary sites of action of µ‐opioid agonists with respect to inhibition of GI function are in the periphery, whereas analgesic activity resides primarily in the CNS.
Peripheral opiate action on afferent fibres supplying the rat intestine
Authors: Grundy D. , Booth C. E. , Winchester W. , Hicks G. A. 
Published: September 2004

AbstractThe aim of the present study was to examine the sensitivity of mesenteric afferents supplying the rat small intestine to µ‐opioid receptor ligands. Mesenteric afferent discharge was recorded electrophysiologically in response to [D‐ALA2, N‐Me‐Phe4, Gly5‐ol]‐enkephalin (DAMGO; 100 µg kg−1 i.v.), before and after treatment with the µ‐receptor antagonist alvimopan (1 mg kg−1 i.v.). DAMGO markedly stimulated whole nerve mesenteric afferent discharge (P < 0.05), an effect completely blocked by alvimopan. The response of mesenteric afferents to 2‐methyl‐5‐hydroxytryptamine (30 µg kg−1 i.v.), bradykinin (0.1–1 µg kg−1 i.a.) and both low‐ and high‐threshold distension (0–60 mmHg) was unaffected by alvimopan. In chronically vagotomized animals, the low‐threshold response to distension was attenuated while the remaining high‐threshold response was unaffected by alvimopan. In conclusion, mesenteric afferent fibres are markedly stimulated by µ‐opioid receptor agonists, an effect blocked by alvimopan, which may contribute to the gastrointestinal reflex and behavioural responses to opiate treatment or abuse. However, alvimopan did not influence the normal sensitivity of intestinal afferents to chemical and mechanical stimuli that activate different subpopulations of vagal and spinal afferents. Thus, alvimopan may be useful for the treatment of gastrointestinal sequelae following opiate treatment for postoperative or chronic pain.
Mechanisms of postoperative ileus
Authors: Bauer A. J. , Boeckxstaens G. E. 
Published: September 2004

AbstractPostoperative ileus is an iatrogenic condition that follows abdominal surgery. Three main mechanisms are involved in its causation, namely neurogenic, inflammatory and pharmacological mechanisms. In the acute postoperative phase, mainly spinal and supraspinal adrenergic and non‐adrenergic pathways are activated. Recent studies, however, show that the prolonged phase of postoperative ileus is caused by an enteric molecular inflammatory response and the subsequent recruitment of leucocytes into the muscularis of the intestinal segments manipulated during surgery. This inflammation impairs local neuromuscular function and activates neurogenic inhibitory pathways, inhibiting motility of the entire gastrointestinal tract. The mechanisms underlying the recruitment of the inflammatory cells, and their interaction with the intestinal afferent innervation, are discussed. Finally, opioids administered for postoperative pain control also contribute to a large extent to the reduction in propulsive gastrointestinal motility observed after abdominal surgery.
Clinical perspective on postoperative ileus and the effect of opiates
Authors: Delaney C. P. 
Published: September 2004

AbstractPostoperative ileus (POI) is a mandatory period of cessation of intestinal function, after abdominal surgery. Over the last decade research has continued into this field, and while we continue to learn about pathogenesis, few controlled data are available for management. The clinical manifestations of POI are reviewed. Management techniques are also reviewed, including the use of postoperative care plans with early ambulation and diet, the effects of epidural anaesthesia, benefits of laparoscopic approaches for intestinal resection, and potential avenues for prevention using novel medications.
Probiotics and human health: a clinical perspective
Authors: Gill H S , Guarner F 
Published: September 2004

Abstract
There is unequivocal evidence that administration of probiotics could be effective in the treatment of acute infectious diarrhoea in children and the prevention of antibiotic associated diarrhoea and nosocomial/community acquired diarrhoea. Encouraging evidence is also emerging for the effectiveness of probiotics in the prevention and management of pouchitis and paediatric atopic diseases, and the prevention of postoperative infections. There is also strong evidence that certain probiotic strains are able to enhance immune function, especially in subjects with less than adequate immune function such as the elderly. Efficacy of probiotics in the prevention of traveller’s diarrhoea, sepsis associated with severe acute pancreatitis, and cancers, the management of ulcerative colitis, and lowering of blood cholesterol remains unproven. In addition to firm evidence of efficacy (for a range of conditions), major gaps exist in our knowledge regarding the mechanisms by which probiotics modulate various physiological functions and the optimum dose, frequency, and duration of treatment for different probiotic strains.
Endocrine emergencies
Authors: Savage M W , Mah P M , Weetman A P , Newell-Price J 
Published: September 2004

Abstract
Diabetic and endocrine emergencies are traditionally treated by the acute medical admitting team or accident and emergency department staff. Most will see diabetic emergencies on a regular basis, as they are common and both type 1 and type 2 disease are increasing in prevalence. Diabetic emergencies are usually easily treated and the patients discharged. However, it is vital not to become complacent as these disorders can lead to death. It is particularly important to follow local guidance and to involve the diabetes team both during and after each episode. Recently it has become clear that about 30% of patients admitted with acute coronary syndrome (including infarction) have either diabetes or “stress hyperglycaemia”; evidence suggests that these patients should be treated not only as a cardiac emergency but also as a diabetic one. Thus, every patient with acute coronary syndrome or acute myocardial infarction needs diabetes to be excluded. The other endocrine emergencies are less common, but in some ways more important simply because of their rarity. A high level of suspicion is often required to make a diagnosis, although some, such as myxoedema coma, are usually obvious. Treatment must be started before the diagnosis can be confirmed. Guidance on making the diagnosis and initiating treatment should be made available on the local NHS intranet for non-endocrinologists to access; and where possible expert advice made available by telephone. The basic management steps in the common diabetic and endocrine emergencies are outlined; this is not a complete list, but rather an insight for those involved in non-selected emergency admissions.
Sentinel lymph node biopsy in breast cancer patients after overnight migration of radiolabelled sulphur colloid
Authors: Lamichhane N , Shen K W , Li C L , Han Q X , Zhang Y J , Shao Z M , Shen Z Z 
Published: September 2004

Abstract
Objective: To evaluate the performance and feasibility of sentinel lymph node biopsy in breast cancer patients using technetium-99m (99mTc) sulphur colloid and gamma probe.
Methods: From May 2000 to March 2001, 70 patients with a tumour less than 5 cm with clinically negative axillary lymph nodes underwent sentinel node biopsy followed by standard axillary dissection. 99mTc sulphur colloid was injected around the primary tumour the day before surgery and a gamma probe was used to detect the sentinel lymph node during the surgical procedure. Sentinel lymph node biopsy was compared with standard axillary dissection for its ability to accurately reflect the final pathological status of the axillary nodes.
Results: The sentinel lymph node was successfully identified in 67 of 70 patients (95.71%). The number of sentinel lymph nodes ranged from 1–5 (mean 1.5) and non-sentinel nodes ranged from 5–22 (mean 13.3). Of the 67 patients with successfully identified sentinel lymph nodes, 43.28% (29/67) were histologically positive. Sensitivity of the sentinel lymph node to predict axilla was 82.75%; specificity was 100%. Positive and negative predictive values were 100% and 88.3% respectively. The sentinel lymph node was falsely negative in five patients, yielding an accuracy of 92.53%. Sentinel lymph node biopsy was more accurate for T1 tumours than for T2 tumours.
Conclusions: The gamma probe guided method after overnight migration of 99mTc sulphur colloid is technically feasible for detecting sentinel lymph nodes in most breast cancer patients, accurately predicting the axillary lymph node status, and appears more accurate for T1 lesions than for larger lesions. This minimally invasive axillary staging procedure represents a major advance in the surgical treatment of breast cancer.
NONLINEAR VACUUM PHENOMENA IN NONCOMMUTATIVE QED
Authors: ALVAREZ-GAUMÉ L. , BARBÓN J. L. F. 
Published: September 2004

We show that the classic results of Schwinger on the exact propagation of particles in the background of constant field-strengths and plane waves can be readily extended to the case of nocommutative QED. It is shown that nonperturbative effects on constant backgrounds are the same as their commutative counterparts, provided the on-shell gauge-invariant dynamics are referred to a nonperturbatively related space–time frame. For the case of the plane wave background, we find evidence of the effective extended nature of noncommutative particles, producing retarded and advanced effects in scattering. Besides the known "dipolar" character of noncommutative neutral particles, we find that charged particles are also effectively extended, but they behave instead as "half-dipoles."
Abnormal regulation of Mg2+ transport via Na/Mg exchanger in sickle erythrocytes
Authors: Rivera Alicia , Ferreira Ana , Bertoni Danielle , Romero José R. , Brugnara Carlo 
Published: September 2004

Abstract
Erythrocyte magnesium (Mg2+) deficiency has been demonstrated in sickle cell disease to contribute to erythrocyte dehydration, K loss, and thus sickling. No studies have assessed the functional properties of the Na/Mg exchanger in sickle cell disease. Using Mg2+-loaded erythrocytes, we measured Mg2+ efflux induced by extracellular Na+. We estimated that the Na/Mg exchanger had higher maximal velocity, higher affinity for Na+, and lower cooperativity for Mg2+ in sickle than in normal erythrocytes. The activity of the exchanger was markedly decreased by hypotonic and hypertonic conditions in normal erythrocytes but not in sickle erythrocytes. Studies of density-separated erythrocytes showed that the activity of the exchanger decreased as the mean cellular hemoglobin concentration increased in normal but not in sickle erythrocytes. Inhibition of protein kinase C (PKC) activity by calphostin C and chelerythrine increased the activity of the exchanger in normal but not in sickle erythrocytes. Inhibition of serine/threonine phosphatases did not affect the activity of the exchanger in either normal or sickle erythrocytes. Altogether, these data indicate that the Na/Mg exchanger is abnormally regulated in sickle erythrocytes. Therefore, Mg2+ depletion in sickle erythrocytes might be mediated by an up-regulated Na/Mg exchanger, possibly by dephosphorylation of the transporter or a closely associated regulator. (Blood. 2005;105:382-386)
Autologous Stem-Cell Transplantation Can Be Performed Safely Without the Use of Blood-Product Support
Authors: Ballen Karen K. , Becker Pamela S. , Yeap Beow Yong , Matthews Barbara , Henry David H. , Ford Patricia A. 
Published: September 2004

Purpose Autologous stem-cell transplantation has been shown to be a curative procedure for a variety of leukemias and lymphomas. Most transplants require RBC and platelet support. We report the ability to perform autologous transplantation without blood-product support. Subjects and Methods In this study, we treated 26 patients with religious objection to blood products with autologous stem-cell support without the use of any blood products. Patients received a combination of granulocyte colony-stimulating factor (G-CSF), erythropoietin, and interleukin-11 or G-CSF alone to mobilize stem cells. Post-transplant patients received intravenous iron, erythropoietin, G-CSF, and epsilon aminocaproic acid. Results There were two major bleeding complications (8%), with two treatment-related deaths (8%). There were three minor bleeding complications (12%). The median fall in hemoglobin level was 4.7 g/dL; the median hemoglobin level 30 days after transplantation was 9.2 g/dL. The median total number of days with platelet count less than 10 × 109/L was 4 days; the median days to platelet recovery greater than 20 × 109/L was 12 days. Conclusion Autologous stem-cell transplantation can be performed safely without the use of any blood products.
Atazanavir
Authors: Orrick Joanne J , Steinhart Corklin R 
Published: September 2004

OBJECTIVE To review the pharmacology, virology, pharmacokinetics, resistance profile, clinical efficacy, safety, and drug interactions of atazanavir. DATA SOURCES A PubMed and NLMGateway search (1966–June 2004) utilizing the key words atazanavir and BMS-232632 was performed. Abstracts from scientific meetings, including the Conference on Retroviruses and Opportunistic Infections, International AIDS Society Conference on HIV Pathogenesis and Treatment, Interscience Conference on Antimicrobial Agents and Chemotherapy, and the Infectious Diseases Society of America, were also reviewed. STUDY SELECTION AND DATA EXTRACTION All publications and meeting abstracts were reviewed, and information relevant to the formulary decision-making process was selected. DATA SYNTHESIS Atazanavir is a once-daily protease inhibitor (PI) that received approval by the Food and Drug Administration in June 2003. In clinical trials in antiretroviral (ARV)-naîve patients, atazanavir had efficacy similar to that of efavirenz or nelfinavir. In ARV-experienced patients, atazanavir was inferior to lopinavir/ritonavir unless atazanavir was coadministered with low-dose ritonavir. Following failure of an atazanavir-containing regimen in ARV-naîve patients, a unique I50L mutation was seen. Atazanavir resistance is likely when resistance to ≥3 PIs is present. Atazanavir can cause increases in unconjugated bilirubin levels, which rarely leads to jaundice or scleral icterus. In contrast to comparators, atazanavir did not negatively impact the lipid profile. Similar to other PIs, atazanavir is metabolized by and inhibits CYP3A at clinically relevant concentrations; therefore, many potential drug interactions exist. CONCLUSIONS Atazanavir is a once-daily PI that, unlike other PIs, does not negatively impact the lipid profile. Atazanavir may be particularly desirable in patients with hyperlipidemia or other coronary artery disease risk factors.
Evaluation of Lamotrigine Toxicity Reported to Poison Centers
Authors: Lofton Amanda L , Klein-Schwartz Wendy 
Published: September 2004

BACKGROUND Lamotrigine is an antiepileptic drug for the treatment of partial and generalized seizures as well as bipolar disorder. Limited published information exists describing the clinical effects of lamotrigine overdose. OBJECTIVE To examine the toxicity of exposures to lamotrigine utilizing national poison center data. METHODS Data on single-substance exposures to lamotrigine reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System in 2000 and 2001 were retrospectively analyzed. RESULTS There were 493 cases that met the inclusion criteria. The majority of exposures occurred within the age groups 20–59 years old (n = 198, 40.2%), followed by 4 years old (n = 173, 35.1%). Overall, the majority of patients (52.1%) exposed to lamotrigine in overdose experienced no toxic clinical effects. The most common clinical effects reported in overdose were drowsiness/lethargy (20.9%), vomiting (11%), nausea (5.1%), ataxia (4.9%), dizziness/vertigo (4.5%), and tachycardia (4.3%). Major clinical effects included coma (n = 6), seizures (n = 8), and respiratory depression (n = 3). Medical outcome was reported as minor in 150 (30.4%), moderate in 73 (14.8%), and major in 13 (2.6%) cases. There were no deaths. CONCLUSIONS These data demonstrate that the majority of patients exposed to lamotrigine in overdose experienced minor or no clinical effects. Although rare, serious effects can also occur.
Intensity of mobile phone use and health compromising behaviours—how is information and communication technology connected to health‐related lifestyle in adolescence?
Authors: Leena Koivusilta , Tomi Lintonen , Arja Rimpelä 
Published: September 2004

AbstractThe association of mobile phone use with health compromising behaviours (smoking, snuffing, alcohol) was studied in a survey comprising a representative sample of 14–16‐year‐olds (N=3485) in 2001. Mobile phone was used by 89% of respondents and by 13% for at least 1 h daily. The intensity of use was positively associated with health compromising behaviours. The associations remained, although somewhat reduced, after including weekly spending money in the models. This study concludes that, at least in the present developmental level of communication technologies, intensive mobile phone use seems to be part of the same health‐related lifestyle as health compromising behaviours.
Role of cytokines and chemokines in prion infections of the central nervous system
Authors: Burwinkel Michael , Riemer Constanze , Schwarz Anja , Schultz Julia , Neidhold Sabine , Bamme Theresa , Baier Michael 
Published: September 2004

AbstractPrion infections of the central nervous system (CNS) are characterised by a reactive gliosis and the subsequent degeneration of neuronal tissue. The activation of glial cells, which precedes neuronal death, is likely to be initially caused by the deposition of misfolded, proteinase K‐resistant, isoforms (termed PrPres) of the prion protein (PrP) in the brain. Cytokines and chemokines released by PrPres‐activated glia cells may contribute directly or indirectly to the disease development by enhancement and generalisation of the gliosis and via cytotoxicity for neurons. However, the actual role of prion‐induced glia activation and subsequent cytokine/chemokine secretion in disease development is still far from clear. In the present work, we review our present knowledge concerning the functional biology of cytokines and chemokines in prion infections of the CNS.
SNAP: workbench management tool for evolutionary population genetic analysis
Authors: Price Eric W. , Carbone Ignazio 
Published: September 2004

Abstract
Summary: The reconstruction of population processes from DNA sequence variation requires the coordinated implementation of several coalescent-based methods, each bound by specific assumptions and limitations. In practice, the application of these coalescent-based methods for parameter estimation is difficult because they make strict assumptions that must be verified a priori and their parameter-rich nature makes the estimation of all model parameters very complex and computationally intensive. A further complication is their distribution as console applications that require the user to navigate through console menus or specify complex command-line arguments. To facilitate the implementation of these coalescent-based tools we developed SNAP Workbench, a Java program that manages and coordinates a series of programs. The workbench enhances population parameter estimation by ensuring that the assumptions and program limitations of each method are met and by providing a step-by-step methodology for examining population processes that integrates both summary-statistic methods and coalescent-based population genetic models.
Availability: SNAP Workbench is freely available at http://snap.cifr.ncsu.edu. The workbench and tools can be downloaded for Mac, Windows and Unix operating systems. Each package includes installation instructions, program documentation and a sample dataset.
Contact: ignazio_carbone@ncsu.edu
Supplementary information: A description of system requirements and installation instructions can be found at http://snap.cifr.ncsu.edu