bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrathecal Opioids and Lower Urinary Tract Function
Authors: Kuipers Peter W. , Kamphuis Ed T. , van Venrooij Ger E. , van Roy John P. , Ionescu Traian I. , Knape Johannes T. , Kalkman Cor J. 
Published: May 2004

Background
Intrathecal administration of opioids may cause lower urinary tract dysfunction. In this study, the authors compared the effects of morphine and sufentanil administered intrathecally in a randomized double-blind fashion (two doses each) on lower urinary tract function in healthy male volunteers.

Methods
Urodynamic evaluation was performed before and every hour after drug administration up to complete recovery of lower urinary tract function using pressure and flow measurements recorded from catheters in the bladder and rectum. Sense of urge and urinary flow rates were assessed every hour by filling the bladder with its cystometric capacity and asking the patient to void. Full recovery was defined as a residual volume of less than 10% of bladder capacity and a maximum flow rate within 10% of the initial value.

Results
Intrathecal administration of both opioids caused dose-dependent suppression of detrusor contractility and decreased sensation of urge. Mean times to recovery of normal lower urinary tract function were 5 and 8 h after 10 or 30 microg sufentanil and 14 and 20 h after 0.1 or 0.3 mg morphine, respectively. This recovery profile can be explained by the spinal pharmacokinetics of both opioids.

Conclusions
Intrathecal opioids decrease bladder function by causing dose-dependent suppression of detrusor contractility and decreased sensation of urge. Recovery of normal lower urinary tract function is significantly faster after intrathecal sufentanil than after morphine, and the recovery time is clearly dose dependent.
Correlation between the Distribution of Contrast Medium and the Extent of Blockade during Epidural Anesthesia
Authors: Yokoyama Masataka , Hanazaki Motohiko , Fujii Hiromi , Mizobuchi Satoshi , Nakatsuka Hideki , Takahashi Toru , Matsumi Masaki , Takeuchi Mamoru , Morita Kiyoshi 
Published: May 2004

Background
If the epidural spread of contrast medium can be well correlated with the spread of local anesthetics, epidurography can predict the dermatomal distribution of the anesthetic block. The authors evaluated the relation between radiographic and analgesic spread.

Methods
An epidural catheter was inserted in 90 patients, and predicted catheter tip position was recorded. The analgesic area was determined by pinprick after a 5-ml injection of 1.5% lidocaine, and epidurography was performed after a 5-ml injection of 240 mg I/ml iotrolan. Patients were assigned to three groups according to catheter tip position (group C: C-T4; group T: T5-T10; group L: T11-L), and patterns of spread were compared. In 16 of 90 subjects, radiographic and analgesic spread was further investigated after an additional 5-ml injection of iotrolan and lidocaine.

Results
The total radiographic spread correlated well with analgesic spread (right side: Y = 0.84 X + 0.16, r = 0.92, P < 0.01; left side: Y = 0.78 X + 0.45, r = 0.91, P < 0.01). The mean radiographic spread in the cephalad and caudal directions from the catheter tip also correlated well with mean analgesic spread (r = 0.97, P < 0.01, each direction). The mean distance between the predicted catheter tip and radiographically determined positions was 1.0 +/- 0.8 segments: the value in group T was significantly larger than that in groups C (P < 0.05) and L (P < 0.01). Although the correlation of radiographic spread with age was statistically significantly (r = 0.39, P < 0.01), great individual variation in spreading pattern was seen. In 16 subjects, mean radiographic spread correlated well with analgesic spread after 5- and 10-ml injections of iotrolan and lidocaine.

Conclusions
Epidurography is useful to indicate epidural catheter position and can help to predict the exact dermatomal distribution of analgesic block.
Phase Ia and Ib Study of Amitriptyline for Ulnar Nerve Block in Humans
Authors: Fridrich Peter , Eappen Sunil , Jaeger Walter , Schernhammer Eva , Zizza Anthony M. , Wang Ging Kuo , Gerner Peter 
Published: May 2004

Background
The antidepressant amitriptyline is used as an adjuvant in the treatment of chronic pain conditions. Among its many actions, this drug also blocks ion channels, such as Na channels. Preliminary animal studies suggested that amitripty-line would be a longer-lasting local anesthetic than bupivacaine, with potentially fewer side effects. Therefore, the authors investigated the adverse effects and effectiveness of this drug when given for ulnar nerve blockade in human volunteers.

Methods
After obtaining written institutional review board approval and informed consent, a typical phase Ia trial was conducted by administration to the ulnar nerve at the level of the wrist in an open-label, dose-escalating fashion. Amitripty-line hydrochloride, 4 ml, at concentrations of 5, 10, and 20 mM (n = 4-9/group) was used for each volunteer. If no major side effects and nerve block were encountered, comparison in a randomized, double-blinded trial of amitriptyline (20 mM) to placebo and bupivacaine (4 mM) (n = 4-9/group), was to follow. A blunt needle was used to grade the pain, and motor blockade was assessed by the Froment test.

Results
There was no significant statistical difference in terms of side effects (pain, swelling, erythema, and sedation) among any groups. The analgesic effects of 20 mM amitriptyline and 4 mm bupivacaine solution were significantly higher than those of the placebo solution.

Conclusions
Because of the lack of evidence that amitripty-line provides better nerve blockade than current local anesthetics and the potential for neurotoxicity, its use for peripheral nerve blockade in humans seems limited.
Production of Paradoxical Sensory Hypersensitivity by α2-Adrenoreceptor Agonists
Authors: Quartilho Aline , Mata Heriberto P. , Ibrahim Mohab M. , Vanderah Todd W. , Ossipov Michael H. , Lai Josephine , Porreca Frank , Malan T. Philip 
Published: May 2004

Background
Administration of opioid receptor agonists is followed by paradoxical sensory hypersensitivity. This hypersensitivity has been suggested to contribute to the antinociceptive tolerance observed with opioids. The authors hypothesized that alpha 2-adrenoreceptor agonists, which also produce antinociceptive tolerance, would produce sensory hypersensitivity.

Methods
alpha 2-Adrenoreceptor agonists were administered to male Sprague-Dawley rats as a single subcutaneous injection, a continuous subcutaneous infusion, a single intrathecal injection, or a continuous intrathecal infusion. Thermal sensitivity was determined using latency to withdrawal of the hind paw from radiant heat. Tactile sensitivity was determined using withdrawal threshold to von Frey filaments. Spinal dynorphin content was measured by enzyme immunoassay.

Results
Single systemic or intrathecal injections of clonidine or dexmedetomidine produced antinociception followed by delayed thermal and tactile hypersensitivity. Six-day systemic or intrathecal infusion of clonidine produced tactile and thermal hypersensitivity observed even during clonidine infusion. Sensory hypersensitivity was prevented by coadministration of the alpha 2-adrenoreceptor-selective antagonist idazoxan or the N-methyl-D-aspartate receptor-selective antagonist MK-801. Six-day infusion of intrathecal clonidine increased dynorphin content in dorsal lumbar spinal cord. MK-801 and dynorphin antiserum reversed clonidine-induced sensory hypersensitivity.

Conclusions
alpha 2-Adrenoreceptor agonists produce sensory hypersensitivity that may be analogous to that produced by opioids. Sensory hypersensitivity was prevented by idazoxan, demonstrating that it is mediated by alpha 2 receptors. Clonidine infusion increased spinal dynorphin content. Sensory hypersensitivity was prevented or reversed by MK-801 and dynorphin antiserum, implicating N-methyl-D-aspartate receptors and spinal dynorphin in its production. Clinicians should be mindful of the possibility of drug-induced hyperalgesia in patients treated with alpha 2-adrenoreceptor agonists.
The ankyrin repeat as molecular architecture for protein recognition
Authors: Mosavi Leila K. , Cammett Tobin J. , Desrosiers Daniel C. , Peng Zheng‐yu 
Published: May 2004

AbstractThe ankyrin repeat is one of the most frequently observed amino acid motifs in protein databases. This protein–protein interaction module is involved in a diverse set of cellular functions, and consequently, defects in ankyrin repeat proteins have been found in a number of human diseases. Recent biophysical, crystallographic, and NMR studies have been used to measure the stability and define the various topological features of this motif in an effort to understand the structural basis of ankyrin repeat‐mediated protein–protein interactions. Characterization of the folding and assembly pathways suggests that ankyrin repeat domains generally undergo a two‐state folding transition despite their modular structure. Also, the large number of available sequences has allowed the ankyrin repeat to be used as a template for consensus‐based protein design. Such projects have been successful in revealing positions responsible for structure and function in the ankyrin repeat as well as creating a potential universal scaffold for molecular recognition.
High resolution crystallographic studies of α‐hemolysin–phospholipid complexes define heptamer–lipid head group interactions: Implication for understanding protein–lipid interactions
Authors: Galdiero Stefania , Gouaux Eric 
Published: May 2004

AbstractThe α‐hemolysin is an archetypal pore‐forming protein that is secreted from Staphylococcus aureus as a water‐soluble monomer. When the monomer binds to the membrane of a susceptible cell, the membrane‐bound molecules assemble into the lytic heptamer. Although a bilayer or a bilayer‐like environment are essential to toxin assembly, there is no high resolution information on toxin–phospholipid complexes. We have determined the structures of detergent‐solubilized α‐hemolysin heptamer bound to glycerophospho‐choline or dipropanoyl glycerophosphocholine at 1.75–1.80 Å resolution and 110 K. The phosphocholine head group binds to each subunit in a crevice between the rim and the stem domains. The quaternary ammonium group interacts primarily with aromatic residues, whereas the phosphodiester moiety interacts with a conserved arginine residue. These structures provide a molecular basis for understanding why α‐hemolysin preferentially assembles on membranes comprised of phosphocholine lipids.
Inhibition of the Class II HMG–CoA reductase of Pseudomonas mevalonii
Authors: Hedl Matija , Rodwell Victor W. 
Published: May 2004

AbstractThere are two structural classes of HMG–CoA reductase, the third enzyme of the mevalonate pathway of isopentenyl diphosphate biosynthesis—the Class I enzymes of eukaryotes and the Class II enzymes of certain eubacteria. Structural requirements for ligand binding to the Class II HMG–CoA reductase of Pseudomonas mevalonii were investigated. For conversion of mevalonate to HMG–CoA the −CH3, −OH, and −CH2COO− groups on carbon 3 of mevalonate were essential for ligand recognition. The statin drug Lovastatin inhibited both the conversion of HMG–CoA to mevalonate and the reverse of this reaction. Inhibition was competitive with respect to HMG–CoA or mevalonate and noncompetitive with respect to NADH or NAD+. Ki values were millimolar. The over 104‐fold difference in statin Ki values that distinguishes the two classes of HMG–CoA reductase may result from differences in the specific contacts between the statin and residues present in the Class I enzymes but lacking in a Class II HMG–CoA reductase.
Scoring profile‐to‐profile sequence alignments
Authors: Wang Guoli , Dunbrack Roland L. 
Published: May 2004

AbstractSequence alignment profiles have been shown to be very powerful in creating accurate sequence alignments. Profiles are often used to search a sequence database with a local alignment algorithm. More accurate and longer alignments have been obtained with profile‐to‐profile comparison. There are several steps that must be performed in creating profile–profile alignments, and each involves choices in parameters and algorithms. These steps include (1) what sequences to include in a multiple alignment used to build each profile, (2) how to weight similar sequences in the multiple alignment and how to determine amino acid frequencies from the weighted alignment, (3) how to score a column from one profile aligned to a column of the other profile, (4) how to score gaps in the profile–profile alignment, and (5) how to include structural information. Large‐scale benchmarks consisting of pairs of homologous proteins with structurally determined sequence alignments are necessary for evaluating the efficacy of each scoring scheme. With such a benchmark, we have investigated the properties of profile–profile alignments and found that (1) with optimized gap penalties, most column–column scoring functions behave similarly to one another in alignment accuracy; (2) some functions, however, have much higher search sensitivity and specificity; (3) position‐specific weighting schemes in determining amino acid counts in columns of multiple sequence alignments are better than sequence‐specific schemes; (4) removing positions in the profile with gaps in the query sequence results in better alignments; and (5) adding predicted and known secondary structure information improves alignments.
Solution structure of the hypothetical protein Mth677 from Methanobacterium thermoautotrophicum: A novel α+β fold
Authors: Blanco Francisco J. , Yee Adelinda , Campos‐Olivas Ramón , Ortiz Ángel R. , Devos Demian , Valencia Alfonso , Arrowsmith Cheryl H. , Rico Manuel 
Published: May 2004

AbstractThe structure of Mth677, a hypothetical protein from Methanobacterium thermoautotrophicum (Mth), has been determined by using heteronuclear nuclear magnetic resonance (NMR) methods on a double‐labeled 15N‐13C sample. Mth677 adopts a novel α+β fold, consisting of two α‐helices (one N terminal and one C terminal) packed on the same side of a central β‐hairpin. This structure is likely shared by its three orthologs, detected in three other Archaebacteria. There are no clear features in the sequences of these proteins or in the genome organization of Mth to make a reliable functional assignment to this protein. However, the structural similarity to Escherichia coli MinE, the protein which controls that division occurs at the midcell site, lends support to the proposal that Mth677 might be, in Mth, the counterpart of the topological specificity domain of MinE in E. coli.
Smad3 as a mediator of the fibrotic response
Authors: Flanders Kathleen C. 
Published: May 2004

SummaryTransforming growth factor‐β (TGF‐β) plays a central role in fibrosis, contributing to the influx and activation of inflammatory cells, the epithelial to mesenchymal transdifferentiation (EMT) of cells and the influx of fibroblasts and their subsequent elaboration of extracellular matrix. TGF‐β signals through transmembrane receptor serine/threonine kinases to activate novel signalling intermediates called Smad proteins, which modulate the transcription of target genes. The use of mice with a targeted deletion of Smad3, one of the two homologous proteins which signals from TGF‐β/activin, shows that most of the pro‐fibrotic activities of TGF‐β are mediated by Smad3. Smad3 null inflammatory cells and fibroblasts do not respond to the chemotactic effects of TGF‐β and do not autoinduce TGF‐β. The loss of Smad3 also interferes with TGF‐β‐mediated induction of EMT and genes for collagens, plasminogen activator inhibitor‐1 and the tissue inhibitor of metalloprotease‐1. Smad3 null mice are resistant to radiation‐induced cutaneous fibrosis, bleomycin‐induced pulmonary fibrosis, carbon tetrachloride‐induced hepatic fibrosis as well as glomerular fibrosis induced by induction of type 1 diabetes with streptozotocin. In fibrotic conditions that are induced by EMT, such as proliferative vitreoretinopathy, ocular capsule injury and glomerulosclerosis resulting from unilateral ureteral obstruction, Smad3 null mice also show an abrogated fibrotic response. Animal models of scleroderma, cystic fibrosis and cirrhosis implicate involvement of Smad3 in the observed fibrosis. Additionally, inhibition of Smad3 by overexpression of the inhibitory Smad7 protein or by treatment with the small molecule, halofuginone, dramatically reduces responses in animal models of kidney, lung, liver and radiation‐induced fibrosis. Small moleucule inhibitors of Smad3 may have tremendous clinical potential in the treatment of pathological fibrotic diseases.
Characterization of the E‐cadherin/catenin complex in colorectal carcinoma cell lines
Authors: El‐Bahrawy Mona , Poulsom S. Richard , Rowan Andrew J. , Tomlinson Ian T. , Alison Malcolm R. 
Published: May 2004

SummaryThe E‐cadherin/catenin complex is a prime mediator of cell–cell adhesion. APC mutations can result in loss of β‐catenin downregulation and an accumulation of β‐catenin in the cell. β‐CATENIN mutations can have a similar effect. The aim of this study was to investigate the effect of β‐CATENIN and APC mutations on the expression and assembly of the E‐cadherin/catenin complex. Five colorectal carcinoma cell lines with different APC and β‐CATENIN gene status were selected and mutations were confirmed. The expression of members of the E‐cadherin/catenin complex was studied by immunohistochemistry and Western blotting. Complex assembly was investigated by immunoprecipitation. It is shown that E‐cadherin and catenins are expressed in colorectal carcinoma cell lines with the predominant complex assembly being E‐cadherin/β‐catenin/α‐catenin. The subcellular distribution of the proteins is influenced by cell–cell contact, resulting in membranous localization. The expression and assembly of the E‐cadherin/catenin complex does not appear to be affected by the presence of APC and or β‐CATENIN mutations.
A population‐based epidemiologic study of irritable bowel syndrome in South China: stratified randomized study by cluster sampling
Authors: Xiong L. S. , Chen M. H. , Chen H. X. , Xu A. G. , Wang W. A. , Hu P. J. 
Published: May 2004

SummaryBackground : The detailed population‐based data on irritable bowel syndrome in South China are lacking.Aims : To assess the prevalence of irritable bowel syndrome in South China and its impact on health‐related quality of life.Subjects and methods : A face‐to‐face interview was carried out in South China to assess the prevalence of irritable bowel syndrome. Random clustered sampling of permanent inhabitants aged 18–80 years was carried out under stratification of urban and suburban areas. The impact of irritable bowel syndrome on health‐related quality of life was evaluated using the Chinese version of SF‐36.Results : A total of 4178 subjects (1907 male and 2271 female) were interviewed. The adjusted prevalence of irritable bowel syndrome in South China is 11.50% according to the Manning criteria and 5.67% according to the Rome II criteria. Factors including history of analgesic use such as non‐steroidal anti‐inflammatory drug (odds ratio 3.83), history of food allergies (odds ratio 2.68), psychological distress (odds ratio 2.18), life events (odds ratio 1.89), history of dysentery (odds ratio 1.63) and negative coping style (odds ratio 1.28) were significantly associated with the presence of irritable bowel syndrome (P < 0.05). Irritable bowel syndrome was significantly associated with a decrement in health‐related quality of life score.Conclusion : Irritable bowel syndrome is a common disorder in South China and has a negative impact on health‐related quality of life.
Serological testing for coeliac disease in patients with symptoms of irritable bowel syndrome: a cost‐effectiveness analysis
Authors: Mein S. M. , Ladabaum U. 
Published: May 2004

SummaryBackground: Patients diagnosed with irritable bowel syndrome may have coeliac disease.Aim: To evaluate the cost‐effectiveness of coeliac disease testing in suspected irritable bowel syndrome.Methods: We used decision analysis to estimate the number of coeliac disease cases detected, quality‐adjusted life‐years gained, and costs resulting from testing suspected irritable bowel syndrome patients for tissue transglutaminase antibody or an antibody panel (tissue transglutaminase, gliadin, total immunoglobulin A). Positive tests prompted endoscopic biopsy. A gluten‐free diet improved quality of life in coeliac disease.Results: Assuming a coeliac disease prevalence of 3%, tissue transglutaminase detected 28 and the panel detected 29 of 30 coeliac disease cases among 1000 suspected irritable bowel syndrome patients. The cost/case detected was $4600 with tissue transglutaminase and $8800 with the panel. The cost/quality‐adjusted life‐year gained with tissue transglutaminase was $7400, and the incremental cost/quality‐adjusted life‐year gained for the panel vs. tissue transglutaminase was $287 000. Tissue transglutaminase cost under $100 000/quality‐adjusted life‐year gained at a coeliac disease prevalence ≥1.1%, assuming a modest utility gain of 0.005 with coeliac disease diagnosis.Conclusions: Testing for coeliac disease in patients with suspected irritable bowel syndrome is likely to be cost‐effective even at a relatively low coeliac disease prevalence and with small improvements in quality of life with a gluten‐free diet.
Cost‐effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C
Authors: Lin O. S. , Keeffe E. B. , Sanders G. D. , Owens D. K. 
Published: May 2004

SummaryBackground : Screening for hepatocellular carcinoma in cirrhotic patients using abdominal ultrasonography and alpha‐foetoprotein levels is widely practiced.Aim : To evaluate its cost‐effectiveness using a Markov decision model.Methods : Several screening strategies with abdominal ultrasonography or computerized tomography and serum alpha‐foetoprotein at 6–12‐month intervals in 40‐year‐old patients with chronic hepatitis C and compensated cirrhosis were simulated from a societal perspective, resulting in discounted costs per quality‐adjusted life‐year saved. Extensive sensitivity analysis was performed.Results : For the least efficacious strategy, annual alpha‐foetoprotein/ultrasonography, the incremental cost‐effectiveness ratio (vs. no screening) was $23 043/quality‐adjusted life‐year. Biannual alpha‐foetoprotein/annual ultrasonography, the most commonly used strategy in the United States, was more efficacious, with a cost‐effectiveness ratio of $33 083/quality‐adjusted life‐year vs. annual alpha‐foetoprotein/ultrasonography. The most efficacious strategy, biannual alpha‐foetoprotein/ultrasonography, resulted in a cost‐effectiveness ratio of $73 789/quality‐adjusted life‐year vs. biannual alpha‐foetoprotein/annual ultrasonography. Biannual alpha‐foetoprotein/annual computerized tomography screening resulted in a cost‐effectiveness ratio of $51 750/quality‐adjusted life‐year vs. biannual alpha‐foetoprotein/annual ultrasonography screening.Conclusions : Screening for hepatocellular carcinoma is as cost‐effective as other accepted screening protocols. Of the strategies evaluated, biannual alpha‐foetoprotein/annual ultrasonography gives the most quality‐adjusted life‐year gain while still maintaining a cost‐effectiveness ratio <$50 000/quality‐adjusted life‐year. Biannual alpha‐foetoprotein/annual computerized tomography screening may be cost‐effective.