bluuebunny/crossref_metadata_2025 huggingface dataset:
Localization of MyoD, myogenin and cell cycle regulatory factors in hypertrophying rat skeletal muscles
Authors: Ishido M. , Kami K. , Masuhara M.
Published: December 2004

Aim:  MyoD, myogenin, proliferating cell nuclear antigen (PCNA) and cyclin‐dependent kinase inhibitor p21 (p21) proteins are key molecules in inducing the growth of myogenic cells in vitro. However, it has not been determined which cell types express these factors in hypertrophying skeletal muscles in vivo.

Methods:  Using immunohistochemical techniques, we examined the spatial and temporal expression patterns of MyoD, myogenin, PCNA and p21 proteins in functionally overloaded rat plantaris muscles induced by ablation of the soleus and gastrocnemius muscles.

Results:  MyoD and myogenin were detected in myonuclei located inside the dystrophin‐positive plasma membrane of myofibres, m‐cadherin‐positive satellite cell nuclei and nuclei located in the interstitial spaces between myofibres on days 1, 3, 5 and 7 post‐surgery. Entry of satellite cells into the cell cycle was indicated by the expression of PCNA on day 3 post‐surgery, and withdrawal from the cell cycle was observed by the expression of p21 in satellite cell nuclei on day 5 post‐surgery. However, the expression of both PCNA and p21 in satellite cell nuclei disappeared on day 7 post‐surgery.

Conclusion:  These results indicate that proliferated satellite cell‐derived myoblasts and undefined myogenic cells located in the interstitial spaces may contribute to an increase in myonuclear number and/or hyperplasia. Furthermore, we provide evidence that all of myonuclei, satellite cells and undefined myogenic cells express both MyoD and myogenin proteins. These results suggest that continual expression of MyoD and myogenin proteins in these cells is an essential molecular event which induces the successful hypertrophy of skeletal muscles.
Leukaemia inhibitory factor alters expression of genes involved in rat cardiomyocyte energy metabolism
Authors: Florholmen G. , Andersson K. B. , Yndestad A. , Austbø B. , Henriksen U. L. , Christensen G.
Published: December 2004

Aim:  Cardiac remodelling is associated with changes in contractile proteins and their performance, alterations in energy production and intracellular calcium homeostasis, as well as changes in extracellular matrix proteins. Some of these processes may be mediated through the gp130 receptor complex. Patients with heart failure have increased cardiac gene expression of leukaemia inhibitory factor (LIF), a cytokine that signals through the gp130 receptor. The aim of this study was to identify alterations in gene expression in LIF‐stimulated neonatal cardiomyocytes.

Methods:  Cardiomyocytes were isolated from 1‐ to 3‐day‐old Wistar rats and stimulated for 48 h with LIF. Gene expression was examined by repeated cDNA filter array analysis (n = 5) and key results verified by complementary methods.

Results:  In LIF‐stimulated cultures we observed increased cell area and changes in gene expression. The intracellular signal regulators signal transducer and activator of transcription 3, calcium/calmodulin‐dependent protein kinase IV, protein kinase Cδ and the transcription factor ID1 were upregulated. Adenylyl cyclase V was downregulated. LIF also induced altered expression of tissue inhibitor of metalloproteinase‐1. Receptor genes for tumour necrosis factor, interleukin‐4, neurotensin and somatostatin were upregulated. Finally, LIF reduced the expression of components in the adenosine triphosphate synthase complex, epidermal fatty acid‐binding protein and insulin‐like growth factor‐binding proteins 1 and 6.

Conclusions:  Array analysis revealed changes in mRNA levels of several genes not previously associated with activation of the gp130/LIF receptor complex. Our findings indicate a role for LIF in regulation of cardiomyocyte energy metabolism.
Changes in PCr/Cr ratio in single characterized muscle fibre fragments after only a few maximal voluntary contractions in humans
Authors: Beltman J. G. M. , Sargeant A. J. , Haan H. , van Mechelen W. , de Haan A.
Published: December 2004

Aim:  This methodological study investigated the number of brief maximal voluntary isometric contractions (MVC) needed to show evidence of fibre activation, as indicated by changes in the phosphocreatine to creatine (PCr/Cr) ratio.

Methods:  Subjects performed series of four, seven and/or 10 MVC (1 s on, 1 s off) of the m. quadriceps (60°‐flexion angle). Biopsy samples of the m. vastus lateralis were taken at rest and immediately post‐exercise. Single muscle fibres were dissected from the freeze‐dried samples and classified as types I, IIA or IIAX, using mATPase stainings. Fragments of characterized fibres were analysed for PCr and Cr content.

Analyses of variance were performed to investigate changes in PCr/Cr per fibre group over time, followed by Bonferroni post‐hoc test (P < 0.01). The fifth percentile of resting values of each fibre group was determined.

Results:  Mean PCr/Cr ratio after four, seven and 10 MVCs were significantly lower for all fibre groups (P < 0.01). The mean decreases were 44, 64 and 76%, respectively. However, only after seven and 10 contractions PCr/Cr ratios of all, but three type I and two type IIAX fibres, individual fibres were below the fifth percentile.

Conclusion:  In very short duration exercise, involving seven brief maximal voluntary contractions, changes in the PCr/Cr ratio indicated activation of different characterized muscle fibre fragments. The results suggest that this approach may be useful for investigating the pattern of fibre type activation in exercise of very short duration.
Hidden Truths: The Politics of Brain, Mind and Soul in Australian Psychiatry
Authors: Halasz George
Published: December 2004

(T)here is no such thing as the scientific mind, but many sorts of scientific mind; there is no such thing as the scientific method, but many sorts of method. There is only one sort of contract which the scientist has, which is with truth, from which he must never knowingly depart.

Professor Sir Dennis Hill (1971) 1
Professionally Indicated Short-Term Risk-Taking in the Treatment of Borderline Personality Disorder
Authors: Krawitz Roy , Jackson Wendy , Allen Ruth , Connell Ann , Argyle Nick , Bensemann Clive , Mileshkin Cris
Published: December 2004

Objective: To define and explore the rationale for professionally indicated short-term risk-taking in treating adults with borderline personality disorder, and discuss prerequisites for the approach, clinical implementation and medicolegal contexts.

Conclusion: When prerequisites are met and clinical and medicolegal practice is sound and thorough, taking short-term risk, as part of a comprehensive treatment, is a legitimate professional consideration in working with some adults with borderline personality disorder.
Obesity in Schizophrenia: What can be Done About it?
Authors: Catapano Lisa , Castle David
Published: December 2004

Objective: To selectively review the literature on obesity in people with schizophrenia.

Conclusions: Obesity is a common problem for people with schizophrenia, with an estimated 40–60% of this population being obese or overweight. Obesity among the mentally ill may contribute to adverse medical and psychological consequences as well as medication non-compliance and poorer quality and enjoyment of life. This review discusses the issues related to obesity in schizophrenia and the role of pharmacological and behavioural treatments in the reduction of obesity and maintenance of gains.
How well Do Australian Medical Schools Prepare General Practitioners to Care for Patients with Mental Disorders?
Authors: Sahhar Deborah , O'Connor Daniel
Published: December 2004

Objective: The purpose of the present paper was to map the mental health workloads of general practitioners (GPs), and to determine GPs' views of the adequacy of their undergraduate training in psychiatry.

Methods: Twenty-nine GPs who had graduated since 1980 from an Australian medical school provided data on 339 consecutive adult patients with conspicuous psychological disorders. After listing their patients’ problems and management plans, doctors rated the value of their undergraduate teaching in preparing them for this task.

Results: Depression, anxiety and substance abuse accounted for 71% of reported cases. Virtually all patients were given some psychologically orientated treatment. Only half were prescribed a psychotropic medication. Nineteen of the 29 doctors wished that they had received more training in counselling.

Conclusions: In an earlier survey it was found that Australian and New Zealand medical school curricula focused largely on the diagnosis and pharmacological management of psychosis and depression. The GPs in the present study most commonly applied psychologically orientated treatments of anxiety, depression and substance abuse. It is proposed that medical schools provide tuition to medical students in counselling.
The patient's Voice in a Problem-Based Learning Case
Authors: Chur-Hansen Anna , Koopowitz Les
Published: December 2004

Objective: Problem-based learning (PBL) relies upon trigger material, often a paper case, to stimulate self-directed enquiry and group discussion. We describe the process of writing a PBL case based upon a patient's narrative account of her experiences of psychiatric illness, and the possible benefits of that collaboration for the patient, as well as for student learning.

Conclusion: Real patients are under-utilized in teaching, as are their narratives, and both are believed to be resources worthy of further attention.
Privacy and Identity in a Changing World
Authors: Harte Angela
Published: December 2004

Objective: To consider the issues of privacy and identity relevant to psychiatric practice in the context of recent technological initiatives and the society that has produced them.

Conclusions: Emerging technologies may have implications for the ways in which Western society relates. These are likely to affect the ways patients present, their concerns and how we may best assist them. Psychiatry may also be of benefit in the evaluation of the privacy implications of new technologies.
Biosynthesis of arginine from citrulline and related compounds by mixed ruminal bacteria, protozoa and their mixture in vitro
Authors: SULTANA Halima , HUSSAIN‐YUSUF Hazizul , ONODERA Ryoji
Published: December 2004

Biosynthesis of arginine (Arg) from citrulline (Cit), ornithine (Orn), proline (Pro), and 5‐aminovaleric acid (5AV) by mixed rumen bacteria (B), protozoa (P), and their mixture (BP) was quantitatively investigated in an in vitro system from the standpoint of protein nutrition in ruminants. Rumen microorganisms, collected from ruminally fistulated goats, were anaerobically incubated with or without 1 mmol/L each of substrates at 39°C for 12 h. Arginine and other related compounds, produced in both supernatants and acid‐hydrolyzates of microorganisms in B, P, and BP suspensions, were analyzed by high‐performance liquid chromatography. Arginine production from Cit in BP, when expressed with a unit of ‘μmol/g microbial nitrogen’, was approximately 70% and 94% higher than that in B and P, respectively, in a 12‐h incubation period. In the case of Orn, the values were approximately 30% and 75%. Both rumen bacteria and protozoa could produce Cit and Orn from Pro, so it is assumed that they can produce Arg from Pro. Rumen protozoa were unable to degrade 5AV and it was the final product in the metabolism of Cit, Orn and Pro in P suspension. A trace amount of Orn and Pro produced from 5AV in B and BP suspensions indicated that the reversible reaction of 5AV formation was performed only by rumen bacteria. This is the first quantitative report on Arg biosynthesis from its precursors by rumen microorganisms.
Development of avian embryo manipulation techniques and their application to germ cell manipulation
Authors: NAITO Mitsuru
Published: December 2004

The development of chicken embryo culture techniques, from single‐cell stage to hatching, makes it possible to manipulate developing embryos at any developmental stage. Production of germline chimeric chickens by the transfer of stage X blastodermal cells or primordial germ cells enables the manipulation of germline cells in vitro. Production of transgenic chickens has been attempted by the retroviral vector method, microinjection of DNA into a fertilized ovum at the single‐cell stage, use of chimeric intermediates produced by the transfer of stage X blastodermal cells or primordial germ cells, manipulation of spermatozoa, and in vivo manipulation of gonads. So far, the only non‐viral method that has successfully produced transgenic chickens is microinjection of DNA into a fertilized ovum. Manipulation of primordial germ cells could become an efficient system for producing transgenic chickens by combining it with the highly efficient transfection method or the in vitro culture system for primordial germ cells. Preservation of avian genetic resources has now become possible by cryopreservation of stage X blastodermal cells or primordial germ cells as well as spermatozoa. The development of nuclear transfer techniques for avian species is necessary.
Scrotal circumference, bodyweight and serum testosterone concentration of Red Sokoto weaner bucks as influenced by dry season crop‐residue supplementation
Authors: MALAU‐ADULI Bunmi Sherifat , EDUVIE Lawrence , LAKPINI Clarence , MALAU‐ADULI Aduli Enoch Othniel
Published: December 2004

The effect of dry season supplementation with crop‐residue‐based rations on bodyweight, scrotal circumference and serum testosterone concentrations in Red Sokoto weaner bucks at 5, 6 and 7 months of age was investigated in the present study. There were 7 treatment groups which were fed a positive control ration (conventional concentrate) fed at 1 and 2% of the bucks’ bodyweights (Rations 1A and 2A), two crop‐residue‐based test rations each fed at 1 and 2% of bodyweight (1B, 2B, 1C and 2C), and a negative control that was unsupplemented (Ration D). All treatment groups had ad libitum access to natural pastures and Digitaria smutsii hay as a basal diet. Bodyweight and scrotal circumference of the bucks significantly increased (P < 0.05) with age from 5.9 kg to 10.2 kg, and 4.40 cm to 6.95 cm, at 5 and 7 months of age, respectively. Bucks on Ration D (unsupplemented group) had the lowest bodyweight and scrotal circumference. Bucks on Ration 2A showed a significant increase in basal testosterone concentration from 0.32 ng/mL at 5 months of age to 0.65 ng/mL at 7 months of age. Peak testosterone concentration also increased from 1.0 ng/mL at 5 months to 2.8 ng/mL at 7 months of age. Bucks on test Ration 2C had higher bodyweights (6.75, 8.00 and 10.00 kg at 5, 6 and 7 months of age, respectively) than bucks on the other test Ration B (6.20, 7.20 and 8.50 kg, respectively). There were no significant differences between the two test rations with regard to scrotal circumferences of the bucks at all ages. However, at 7 months of age, bucks on test Ration 2C had significantly higher peak testosterone concentration (1.80 ng/mL) than their counterparts on test Ration 2B (1.30 ng/mL). The secretory patterns of testosterone were episodic and pulsatile in nature. It was concluded that crop‐residue supplementation in prepubertal Red Sokoto bucks has a significant influence on their bodyweight, scrotal circumference and testosterone production. Test Ration C was a cheap, affordable and better crop‐residue‐based ration for optimal reproductive performance than test Ration B.
Change of plasma insulin‐like growth factor‐1 (IGF‐1) concentration with early growth in Japanese beef cattle
Authors: SUDA Yoshihito , NAGAOKA Kentaro , NAKAGAWA Kazuki , CHIBA Takashi , YUSA Fumihiro , SHINOHARA Hisashi , NIHEI Akira , YAMAGISHI Toshihiro
Published: December 2004

The aim of the present study was to examine the change in plasma insulin‐like growth factor‐1 (IGF‐1) concentration with early growth, changes of bodyweight (BW) and relative dairy gain (RDG) in the pre‐ (PRW) and postweaning periods (POW) in Japanese beef cattle, and relationships with metabolites. A total of 33 calves, 22 Japanese black, 6 Japanese shorthorn and 5 of their crossbreed were studied. Insulin‐like growth factor‐1 and metabolite (glucose, triacylglycerol, nonesterified fatty acid) levels in the plasma, from jugular vein blood taken every month, were measured along with BW. Insulin‐like growth factor‐1 in POW increased dramatically with increase of BW (P < 0.05), and the correlation was positive at 0.52 (P < 0.01). Glucose levels correlated significantly with BW, RDG and IGF‐1 (P < 0.01). Metabolic required calorie correlated positively with IGF‐1 (P < 0.01). Also, correlations of BW in POW, with BW and RDG in PRW were positive (P < 0.01). Growth in PRW would be influenced by maternal effects, while active self‐secretion of IGF‐1 in POW might contribute to POW growth. These factors suggested that to increase growth in PRW, maintaining enough maternal effect and IGF‐1 level in POW, was important for establishing better growth after weaning.
Protective effect of sodium glutamate and sorbitol on thermal denaturation of chicken and croaker actomyosin
Authors: KAWAKAMI Kouji , NEUPANEY Dhanapati , SAMEJIMA Kunihiko
Published: December 2004

The thermal protective effect (E‐Value) of sodium glutamate (Na‐Glu) on chicken and croaker actomyosin (AM) was significant but decreased slightly with increasing concentration. The E‐value of chicken AM with Na‐Glu was 1.11 mol/L−1 at 0–0.75 mol/L and decreased to 0.4 mol/L−1 at 0.75–1.5 mol/L. Likewise, the E‐value of croaker AM with Na‐Glu was 1.51 mol/L−1 at 0–1 mol/L and decreased to 0.2 mol/L−1 at 1–1.5 mol/L. Sorbitol showed a steady thermal protective effect on chicken and croaker AM. The E‐values of chicken and croaker AM at 0 to 1.5 mol/L sorbitol were 0.71 mol/L−1 and 0.59 mol/L−1, respectively. The protective effect of sorbitol on both types of AM was greater than that of Na‐Glu. Higher concentrations of Na‐Glu with chicken and croaker AM gave a decrease in viscosity number and turbidity. Higher concentrations of Na‐Glu caused internal aggregation of AM and the protective effect of Na‐Glu was decreased. The results of this experiment confirmed that Na‐Glu and sorbitol have different modes of action and ability to control the thermal denaturation of chicken and croaker AM.
Factors affecting egg production and layer bird mortality in private poultry farms in the subhumid zone of Nigeria
Authors: MALAU‐ADULI Aduli Enoch Othniel , BAWA Gideon Shaibu , JOEL Kayode
Published: December 2004

Egg production and layer bird mortality data obtained from five different private farms in Zaria within the subhumid zone of Nigeria, over a 6‐year period (1994–1999) were subjected to least squares analysis to determine the effects of age, season and year. It was demonstrated that age had a highly significant influence (P < 0.01) on egg production in that birds falling within the age group 30–39 weeks produced the highest number of eggs (3255 ± 109), while birds over 100 weeks of age produced the lowest number of eggs (1206 ± 412). Similarly, seasonal variation in egg production was also significant (P < 0.05); the highest egg production (2926 ± 90) was obtained during the early dry season, and the lowest (2423 ± 95) during the late wet season. Mortality was generally low (0.0–0.9%) and not significantly different from 20 to 49 weeks of age (P > 0.05). However, from 50 to 100 weeks of age, highly significant differences (P < 0.01) in mortality were observed, with the 90–100 weeks age group recording the highest mortality of 15.7 ± 1.3%. Furthermore, yearly variations in egg production and mortality were highly significant (P < 0.01) with 1999 producing the most eggs (4410 ± 102) and recording the lowest mortality (1.4%). It was concluded that due to the significant seasonal, age and yearly variations, data on egg production and mortality need to be adjusted for these effects to enable unbiased comparison between and within farms. Furthermore, farmers can make adequate feeding preparations commensurate with each season for optimal egg production.
Analysis of energy metabolism and mechanism of loop diuretics in the thick ascending limb of Henle's loop in dog kidneys
Authors: Kiil F. , Sejersted O. M.
Published: December 2004

Aim: The thick ascending limb of Henle's loop (TALH) absorbs up to 40% of filtered NaCl in volume‐expanded dogs. To examine if a fraction of this absorption is passive, NaHCO3 absorption and associated NaCl absorption in proximal tubules were inhibited by acetazolamide, a carbonic anhydrase inhibitor.

Results: Ouabain, a specific inhibitor of Na,K‐ATPase activity, reduced the remaining NaCl absorption and renal oxygen consumption in a ratio ΔNa/ΔO2 = 18, as expected for active transport. However, the responses to two loop diuretics were ΔNa/ΔO2 = 24 for ethacrynic acid and ΔNa/ΔO2 = 30 for bumetanide. Both loop diuretics induced potassium secretion. By superimposing ouabain potassium secretion was stopped and ΔNa/ΔO2 = 18 restored. Replacement of half of the circulating NaCl with Na2SO4 gave stop‐flow pattern similar to those obtained after ethacrynic acid.

Conclusions: Low entry of some sodium ions thorugh the apical membrane is permitted despite low chloride supply or blockade by loop diuretics of chloride entry by the Na‐K‐2Cl transporter. Continued Na‐K‐ATPase activity causes secretion of potassium ions through the apical ion channel, ethacrynic acid being more kaliuretic and less natriuretic than bumetanide. Greater paracellular recycling of sodium ions after bumetanide maintains ionic balance. In contrast, under normal conditions excess entry of chloride by the Na‐K‐2Cl‐transporter leads to paracellular back‐diffusion of chloride rather than paracellular absorption of sodium ions, consistent with ΔNa/ΔO2 = 18 after ouabain. Thus all NaCl transport along TALH is active in vivo, whereas absorption of other cations, such as lithium, probably is passive.
Interactions between COX‐2 and the renin–angiotensin system in the kidney
Authors: Harris R. C.
Published: December 2004

Aim:  In adult mammalian kidney, COX‐2 expression is found in a restricted subpopulation of cells. The two sites of renal COX‐2 localization detected in all species to date are the macula densa (MD) and associated cortical thick ascending limb cells (cTALH) and medullary interstitial cells. Physiological regulation of COX‐2 in these cellular compartments suggests functional roles for eicosanoid products of the enzyme. In the MD region, COX‐2 expression increases in high renin states [salt restriction, angiotensin converting enzyme (ACE) inhibition, renovascular hypertension], and selective COX‐2 inhibitors significantly decrease plasma renin levels and renal renin activity and mRNA expression. An important role for COX‐2‐derived prostanoids in regulation of renin expression and secretion has also been determined by using mice with selective genetic deletion of either the COX‐1 or COX‐2 gene. There is evidence for negative regulation of MD/cTALH COX‐2 by angiotensin II and by glucocorticoids and mineralocorticoids, suggesting that in the kidney, cortical COX‐2 expression is regulated in part by alterations in activity of the renin–angiotensin system.
Regulation of cyclooxygenase‐2 in renal medulla
Authors: Yang T.
Published: December 2004

Aim: 

Renal medulla is a major site for production and action of prostaglandins (PGs). The renal medullary functions as well as structural integrity are in part dependent on PGs under certain physiological or pathophysiological conditions. The two COX isoforms, COX‐1 (constitutive form) and COX‐2 (inducible form) are both abundantly expressed in renal inner medulla at basal state, raising a question of which COX isoform may mediate the known functions of PGs in the region. As in many other cell types, COX‐1 expression in renal medulla is unlikely subject to robust regulation. In contrast, COX‐2 expression in renal medulla is markedly stimulated by chronic salt loading, dehydration and endotoxaemia
in vivo
. At cellular levels, the signalling pathways responsible for the COX‐2 stimulation in renal medullary cells seem to involve both the mitogen‐activated protein kinases and NF‐
κ B. It is likely that in response to various insults that are detrimental to renal medulla, the induction of PG synthesis may become more dependent on COX‐2 than COX‐1, and this phenomenon may be relevant to the cytoprotective response against the insults.
Differences in the renal dopaminergic system activity between Wistar rats from two suppliers
Authors: Sampaio‐Maia B. , Serrão P. , Vieira‐Coelho M. A. , Pestana M.
Published: December 2004

Aim:  Dopamine of renal origin reduces tubular sodium reabsorption and controls blood pressure. The present study evaluated renal dopaminergic activity and its response to uninephrectomy in Wistar Han rats from two suppliers, Harlan (W‐H) and Charles River (W‐CR).

Results:  After uninephrectomy, the fractional excretion of sodium (FENa+) increased in both W‐CR and W‐H rats (W‐CR: from 0.17 ± 0.01 to 0.27 ± 0.02%; W‐H: from 0.39 ± 0.04 to 0.54 ± 0.04%, P < 0.05); however, in W‐CR rats the FENa+ was lower than in W‐H rats in both Sham and uninephrectomized (Unx) animals (P < 0.05). Systolic blood pressure in Unx W‐CR rats was higher than in Unx W‐H animals (131 ± 3 vs. 122 ± 2 mmHg, P < 0.05). Uninephrectomy was accompanied in W‐H rats by increases in urinary levels (nmol g kidney−1 day−1) of dopamine (10.3 ± 0.5 vs. 8.3 ± 0.7, P < 0.05) and 3,4‐dihydroxyphenylacetic acid (DOPAC) (30.5 ± 3.7 vs. 21.3 ± 1.4, P < 0.05) and increases (P < 0.05) in maximal velocity values (Vmax in nmol mg prot−1 15 min−1, 325 ± 12 vs. 265 ± 3) for renal aromatic L‐amino acid decarboxylase (AADC), the enzyme responsible for the synthesis of renal dopamine. By contrast, in W‐CR rats uninephrectomy did not change either the urinary levels of dopamine (7.1 ± 0.5 vs. 7.6 ± 0.7) and DOPAC (25.0 ± 1.9 vs. 24.8 ± 4.1) or AADC activity (Vmax 199 ± 3 vs. 193 ± 9). The Vmax values for renal AADC in W‐CR rats were lower than those found in corresponding W‐H animals.

Conclusion:  Wistar rats from different suppliers represent an important source of variability in the renal dopaminergic system activity. This may contribute to differences in sodium balance and blood pressure control in response to uninephrectomy.
Exercise‐induced HSP27, HSP70 and MAPK responses in human skeletal muscle
Authors: Thompson H. S. , Maynard E. B. , Morales E. R. , Scordilis S. P.
Published: December 2004

Aim:  The present work examined protein and messenger RNA (mRNA) expression of intramuscular heat shock protein 27 (HSP27), heat shock cognate (HSC70) and HSP70 in human biceps brachii (BB) and vastus lateralis (VL) subsequent to two different exercises.

Methods:  Untrained subjects performed 50 high‐force eccentric contractions with their non‐dominant BB and ran downhill (−10°) for 30 min. The 48‐h PX stress response was evaluated with immunoblotting and reverse transcriptase‐polymerase chain reaction (RT‐PCR). Muscle damage was indicated indirectly at 48 h post‐exercise (PX) [loss of mobility, muscle soreness and serum creatine kinase (CK) activity].

Results:  On the protein level, HSP27 and HSP70 increased significantly PX in the BB (384 and 227%, respectively; P < 0.01), but there were no significant HSP changes in the VL or in HSC70 in either muscle. The RT‐PCR data complemented these findings: BB HSP27 and HSP70C mRNA levels increased (135 and 128%, respectively; P < 0.05); in the VL only HSP70B increased (206%; P < 0.05). Phosphorylation of e‐jun NH2‐terminal kinase (JNK) and extracellular regulated kinase (ERK) increased significantly in the BB (226 and 200%, respectively; P < 0.05) but not in the VL, indicating activation of these pathways only after the resistance exercise.

Conclusion:  These data indicate that the PX HSP and mitogen‐activated protein kinase responses are exercise‐specific and local, not systemic. Further, only the resistance exercise induced HSP expression (protein and mRNA) and JNK/ERK activation at 48 h PX, suggesting that these molecules may be important to long‐term skeletal muscle adaptations such as hypertrophy.
Differences in electrophysiological and contractile properties of mammalian cardiac tissues bathed in bicarbonate – and HEPES‐buffered solutions
Authors: Fülöp L. , Szigeti G. , Magyar J. , Szentandrássy N. , Ivanics T. , Miklós Z. , Ligeti L. , Kovács A. , Szénási G. , Csernoch L. , Nánási P. P. , Bányász T.
Published: December 2004

Aim: 
The aim of this study was to compare the action potential configuration, contractility, intracellular Ca2+ and H+ concentrations in mammalian cardiac tissues bathed with Krebs and Tyrode solutions at 37 °C.

Results:  In Langendorff‐perfused guinea‐pig hearts, loaded with the fluorescent Ca2+‐indicator Fura‐2, or H+‐sensitive dye carboxy‐SNARF, shifts from Krebs to Tyrode solution caused intra‐cellular acidification, increased diastolic pressure and [Ca2+]i, decreased systolic pressure and [Ca2+]i, leading to a reduction in the amplitude of [Ca2+]i transients and pulse pressure. Contractility was also depressed in canine ventricular trabeculae when transferred from Krebs to Tyrode solution. Shifts from Krebs to Tyrode solution increased the duration of action potentials in multicellular cardiac preparations excised from canine and rabbit hearts but not in isolated cardiomyocytes. All these changes in action potential morphology, contractility, [Ca2+]i and [H+]i were readily reversible by addition of 26 mmol L−1 bicarbonate to Tyrode solution. Effects of dofetilide and CsCl, both blockers of the delayed rectifier K current, on action potential duration were compared in Krebs and Tyrode solutions. Dofetilide lengthened rabbit ventricular action potentials in a significantly greater extent in Tyrode than in Krebs solution. Exposure of canine Purkinje fibres to CsCl evoked early after depolarizations within 40 min in all preparations incubated with Tyrode solution, but not in those bathed with Krebs solution.

Conclusion:  It is concluded that the marked differences in action potential morphology, [Ca2+]i, [H+]i and contractility observed between preparations bathed with Krebs and Tyrode solutions are more likely attributable to differences in the intracellular buffering capacities of the two media.
Bile acid therapy versus placebo before and after extracorporeal shock wave lithotripsy of gallbladder stones
Authors:   THE EAST‐DANISH GALLSTONE STUDY GROUP
Published: December 2004

Aim: To study the effects of bile acid therapy on the fragmentation rate of cholesterol gallbladder stones by extracorporeal shock wave lithotripsy (ESWL) and on the clearance of fragments after ESWL.

Patients and methods: One hundred and two patients with biliary pain, between one and five radiolucent gallbladder stones, and a gallbladder with a patent cystic duct were randomized to 3 weeks of double‐blind treatment with bile acids (ursodeoxycholic acid 500 mg and chenodeoxycholic acid 500 mg per day) or placebo before ESWL. After successful fragmentation by ESWL (largest fragment 5 mm) the patients were re‐randomized to 6‐month double‐blind therapy with bile acids or placebo.

Results: Ninety‐nine patients completed 3 weeks of pre‐ESWL treatment. There was no statistically significant difference in fragmentation rate between the two groups. After 6 months of post‐ESWL therapy, 12 of 49 patients (24%) had cleared the fragments from their gallbladder with bile acids compared with five of 50 patients (10%) who had placebo therapy (P=0.10). There was no significant difference in the occurrence of pain between groups. The figures were no better in patients with a single stone 20 mm in diameter.

Conclusion: Extracorporeal shock wave lithotripsy with or without adjuvant bile acid therapy does not seem to be an attractive therapy for patients with uncomplicated symptomatic gallstone disease.
A cost‐effectiveness analysis of peginterferon alfa‐2b plus ribavirin for the treatment of naive patients with chronic hepatitis C
Authors: Buti M. , Medina M. , Casado M. A. , Wong J. B. , Fosbrook L. , Esteban R.
Published: December 2004

Aim : To estimate the cost‐effectiveness of therapy and analyse the effect of therapy compliance in naive patients with chronic hepatitis C.

Methods : A decision analysis using the Markov model was performed for four different therapeutic strategies using peginterferon alfa‐2b plus ribavirin or interferon alfa‐2b plus ribavirin. Clinical data were obtained from available published reports and from the Spanish health system perspective.

Results : The incremental cost‐effectiveness ratio of peginterferon alfa‐2b plus ribavirin at a fixed dose, compared with interferon alfa‐2b plus ribavirin, was 8478 euros per life year saved and 3737 euros per quality‐adjusted life year gained. Good therapeutic compliance and weight‐adjusted doses of ribavirin decreased the incremental cost‐effectiveness ratio to 1636 euros per life year saved and 721 euros per quality‐adjusted life year gained. In compliant genotype 1 patients, the incremental cost‐effectiveness ratio decreased to 916 euros per life year saved and 404 euros per quality‐adjusted life year gained, with an increase from 64 to 69 years in the threshold age at which therapy was cost‐effective. The sensitivity analysis demonstrated that changes in the values of the most relevant parameters do not modify the study outcomes.

Conclusion : From the clinical and pharmaco‐economics perspective, the use of decision therapeutic analysis models suggests that the most effective therapy for chronic hepatitis C is peginterferon alfa‐2b plus ribavirin adjusted to patient body weight and with good compliance, particularly in genotyped patients.
Oesophageal cancer and cachexia: the effect of short‐term treatment with thalidomide on weight loss and lean body mass
Authors: Khan Z. H. , Simpson E. J. , Cole A. T. , Holt M. , Macdonald I. , Pye D. , Austin A. , Freeman J. G.
Published: December 2004

Background : Cachexia is common in patients with advanced cancer and has a direct impact on well‐being and mortality.

Aim : To test the hypothesis that thalidomide can promote weight gain and lean body mass in patients with advanced oesophageal cancer.

Methods : In an open‐label study, 11 patients with non‐obstructing and inoperable oesophageal cancer were established on an isocaloric diet for 2 weeks, followed by 2 weeks on thalidomide, 200 mg daily. The primary end‐points were weight change and lean body mass. Secondary end‐points were quality of life and changes in resting energy expenditure.

Results : Ten patients completed the study protocol. The average caloric intake remained the same throughout the study period in all patients. Nine of 10 patients (95% confidence interval, 0.60, 0.98) lost weight on diet alone. The mean weight gain on thalidomide in the following 2 weeks was 1.29 kg (median, 1.25 kg). A similar trend was shown in the lean body mass. Eight of nine patients (95% confidence interval, 0.57, 0.98) initially lost lean body mass on diet alone (missing data in one patient). The mean gain in lean body mass on thalidomide in the following 2 weeks was 1.75 kg (median, 1.33 kg).

Conclusions : Thalidomide treatment appeared to reverse the loss of weight and lean body mass over the 2‐week trial period.
Pruritus in cholestatic and other liver diseases
Authors: Mela M. , Mancuso A. , Burroughs A. K.
Published: December 2004

Pruritus is often the most troublesome symptom in patients with chronic liver disease, particularly when cholestasis is a prominent feature.

The exact pathogenesis is unknown, but empirical treatment, such as cholestyramine, based on a liver‐based origin of pruritus, has been used for many years. Recently, evidence for a central mechanism for pruritus has been obtained and opioid antagonists have been tried clinically with some benefit, but their use is not widespread. In addition, the pruritus associated with intrahepatic cholestasis of pregnancy can now be alleviated in many cases by ursodeoxycholic acid. As it also improves foetal outcome, this should become first‐line therapy.

We review the pathogenesis and therapy of pruritus, highlighting practical aspects to help with patients with seemingly intractable pruritus.
Esomeprazole 20 mg and lansoprazole 15 mg in maintaining healed reflux oesophagitis: Metropole study results
Authors: Lauritsen K. , Devière J. , Bigard M.‐A. , Bayerdörffer E. , Mózsik G. , Murray F. , Kristjánsdóttir S. , Savarino V. , Vetvik K. , De Freitas D. , Orive V. , Rodrigo L. , Fried M. , Morris J. , Schneider H. , Eklund S. , Larkö A.
Published: December 2004

Aim : To compare the efficacy of esomeprazole, 20 mg once daily, vs. lansoprazole, 15 mg once daily, for the maintenance treatment of patients with healed reflux oesophagitis.

Methods : During the initial open healing phase, 1391 patients with endoscopically verified reflux oesophagitis and a history of heartburn, with or without acid regurgitation, received esomeprazole 40 mg for 4–8 weeks. Patients who were healed (identified by endoscopy at 4 or 8 weeks) and symptom free were then randomized to receive 6 months of treatment with esomeprazole, 20 mg once daily, or lansoprazole, 15 mg once daily.

Results : Esomeprazole, 20 mg once daily, maintained a significantly higher proportion of patients in remission than lansoprazole, 15 mg once daily, over 6 months [83% (95% CI, 80–86%) of esomeprazole recipients compared with 74% (95% CI, 70–78%) of lansoprazole recipients; P < 0.0001; life table estimates]. When data were analysed according to baseline Los Angeles grade classification, esomeprazole, 20 mg once daily, achieved consistently higher remission rates across all grades of disease severity, whereas the efficacy of lansoprazole decreased to a greater extent with increasing severity of reflux oesophagitis.

Conclusion : Esomeprazole, 20 mg once daily, is more effective than lansoprazole, 15 mg once daily, in maintaining remission in patients with healed reflux oesophagitis.
General practitioner and hospital specialist attitudes to functional gastrointestinal disorders
Authors: Gladman L. M. , Gorard D. A.
Published: December 2004

Background : Functional gastrointestinal symptoms generate a large workload in primary care. Research on functional gastrointestinal disorders is focused on hospital patients, but these patients may differ from those managed in primary care.

Aim : To investigate any differences in attitudes of general practitioners and hospital specialists towards functional gastrointestinal illnesses.

Methods : A questionnaire was sent to 200 general practitioners and 200 British Society of Gastroenterology members.

Results : The response rate was 76%. Sixty‐two general practitioners believed that functional gastrointestinal symptoms represented a ‘real’ currently unexplained gastrointestinal disorder, and 67 believed such symptoms probably represented somatization of a psychological illness. In contrast, most consultants (120) believed that functional gastrointestinal symptoms represented a ‘real’ gastrointestinal disorder, with only 36 perceiving them to have a psychological basis (χ2 = 26.7, P < 0.001). More consultants than general practitioners believed that the understanding of functional gastrointestinal disorders had improved in the last 20 years (χ2 = 4.31, P < 0.05). Most consultants and most general practitioners thought that treatment for these disorders had not improved over this period. Only 21% of general practitioners had heard of the Manning criteria for the diagnosis of irritable bowel syndrome, compared to 81% of consultants (χ2 = 107, P < 0.0001); 12% of general practitioners and 83% of consultants had heard of the Rome criteria for the diagnosis of functional gastrointestinal disorders (χ2 = 154, P < 0.0001); 37% of consultants used the Manning criteria and 40% used the Rome criteria; 11% of general practitioners used the Manning criteria and 3% used the Rome criteria.

Conclusions : General practitioners and consultants have differing views on functional gastrointestinal disorders. In both primary and secondary care, most doctors do not use diagnostic criteria. Further research on the factors used to diagnose functional gastrointestinal disorders in primary care is warranted.
Safety and efficacy of 7‐day rabeprazole‐ and omeprazole‐based triple therapy regimens for the eradication of Helicobacter pylori in patients with documented peptic ulcer disease
Authors: Hawkey C. J. , Atherton J. C. , Treichel H. C. , Thjodleifsson B. , Ravic M.
Published: December 2004

Aim : A double‐blind, randomized study was designed to determine whether rabeprazole‐ and omeprazole‐based triple therapy regimens are therapeutically equivalent in the eradication of Helicobacter pylori.

Methods : Three hundred and forty‐five patients with current or previously active peptic ulcer and a positive H. pylori urease test were randomly assigned to receive RCA, OCA, RCM or OCM twice daily for 7 days (R, rabeprazole 20 mg; O, omeprazole 20 mg; C, clarithromycin 500 mg; A, amoxicillin 1000 mg; M, metronidazole 400 mg). H. pylori eradication was documented by negative 13C‐urea breath tests at 4 and 12 weeks, and was evaluated using a 2 × 2 factorial design with proton pump inhibitor and antibiotic as factors.

Results : Overall eradication rates (per protocol/intention‐to‐treat) were 87%/77% and 85%/75% with rabeprazole and omeprazole, respectively (not significant). However, a statistical interaction between proton pump inhibitor and antibiotic was identified. RCA produced a somewhat higher eradication rate than OCA (94% vs. 84%; difference, 9.8%; 95% confidence interval, − 0.7% to + 20.4%), whereas RCM produced a lower eradication rate than OCM (79% vs. 86%; difference, 8.1%; 95% confidence interval, − 21.4% to + 5.1%). Ulcer healing rates were > 90% with H. pylori eradication. Each regimen was well tolerated.

Conclusions : Rabeprazole‐ and omeprazole‐based triple therapy regimens are therapeutically equivalent in the eradication of H. pylori and well tolerated. The statistical interaction observed between the proton pump inhibitor and supplementary antibiotic may be due to chance.
Pancreatic function testing
Authors: Chowdhury R. S. , Forsmark C. E.
Published: December 2004

Pancreatic function tests are most commonly used to diagnose chronic pancreatitis. These tests include tests which document exocrine or endocrine gland insufficiency and tests which instead measure gradations of decreased secretory capacity. The tests in the former category generally become abnormal when advanced, longstanding chronic pancreatitis is present. Tests in the latter category, however, have the potential to detect chronic pancreatitis at an earlier stage than other available diagnostic tests, including commonly used imaging tests such as computed tomography and endoscopic retrograde cholangiopancreatography. This potential advantage of diagnostic sensitivity is, however, counterweighed by the fact that these tests which measure stimulated secretory capacity are only available at a very few referral centres. This article will review the variety of pancreatic function tests and describe their rationale, accuracy, cost, and clinical usefulness.
Health‐related anxiety and the effect of open‐access endoscopy in US patients with dyspepsia
Authors: Quadri A. , Vakil N.
Published: December 2004

Background : The role of endoscopy in dyspepsia is the subject of debate. The detection of lesions is infrequent, but patients may benefit from the knowledge that the examination is normal. We sought to determine the prevalence of health‐related anxiety in dyspeptic patients referred for open‐access endoscopy and to investigate the effect of endoscopy on health‐related anxiety.

Methods : Consecutive patients referred for open‐access endoscopy from primary care were studied using a validated questionnaire for health‐related anxiety before and after endoscopy, at 1 month and 6 months. Symptoms were assessed using a validated questionnaire at 1 and 6 months.

Results : One hundred and nine patients were studied (69 women and 40 men; mean age, 49 ± 15 years). Thirty‐six of the 109 patients (33%) had high anxiety scores at baseline (mean score, 41 ± 1), which decreased after endoscopy to 35 ± 1 (P < 0.05). The changes persisted at 1 month (33 ± 1) and 6 months (33 ± 1). Endoscopic findings were as follows: normal examination, 120; erosive oesophagitis, 11 (Grade A); erosive duodenitis (all Helicobacter pylori‐negative), 6. Scales for preoccupation with health and fear of illness and death showed significant improvement after endoscopy, and the effects were preserved for 6 months. Anxiety scores in our population were substantially higher than in a corresponding UK population.

Conclusions : Health‐related anxiety is common in dyspeptic patients referred for endoscopy. Endoscopy decreases the preoccupation with health and fear of illness and death in patients with severe anxiety, and the effects persist for 6 months.
Abdominal and pelvic surgery in patients with irritable bowel syndrome
Authors: Hasler W. L. , Schoenfeld P.
Published: December 2004

Aim : To systematically review research on the prevalence of abdominal and pelvic surgery in patients with irritable bowel syndrome.

Methods : Computer searches of MEDLINE, EMBASE and Current Contents were performed independently by both investigators to identify appropriate studies. Primary study selection criteria included: (i) population‐based samples of adult irritable bowel syndrome patients; (ii) the use of appropriate symptom‐based criteria to identify irritable bowel syndrome patients; and (iii) comparison of the prevalence of abdominal and pelvic surgery in irritable bowel syndrome patients vs. control populations. Secondary analysis was performed on published studies of referral populations and case series.

Results : Two population‐based studies met the primary study selection criteria and revealed an increased prevalence of surgery in irritable bowel syndrome patients vs. controls for cholecystectomy (4.6% vs. 2.4%, respectively; odds ratio, 1.9; 95% confidence interval, 1.2–3.2) and hysterectomy (18% vs. 12%, respectively; odds ratio, 1.6; 95% confidence interval, 1.1–2.2). Secondary analysis revealed an increased prevalence of appendectomy and other abdominal and pelvic surgery in irritable bowel syndrome patients.

Conclusions : Irritable bowel syndrome is associated with a disproportionately high prevalence of abdominal and pelvic surgery, but most studies exhibit sub‐optimal study design and do not define the factors causing the increased prevalence of surgery in these patients.
Therapeutic value of a gastroenterology consultation in irritable bowel syndrome
Authors: Ilnyckyj A. , Graff L. A. , Blanchard J. F. , Bernstein C. N.
Published: December 2004

Background : Functional patients comprise the largest group in gastroenterology practice. Pharmacological therapy of irritable bowel syndrome is disappointing. One treatment strategy for irritable bowel syndrome emphasizes the physician's role; the physician is promoted as the therapeutic modality.

Aim : To determine the therapeutic value of the contemporary approach to irritable bowel syndrome by examining health care utilization and patient morbidity.

Methods : We performed an observational study over 4 years using an administrative database and morbidity scales. Health care utilization was assessed for 2 years pre‐ and post‐intervention. Patient morbidity was assessed at baseline and 1 and 2 years post‐intervention. The participants included 70 irritable bowel syndrome patients referred by primary physicians. A structured consultation was performed, establishing a positive diagnosis of irritable bowel syndrome and providing disease conceptualization.

Results : Health care utilization for gastrointestinal diagnoses increased in the year prior to the intervention and declined immediately after to baseline; psychiatric and other visits remained unchanged for 4 years. Pain was reduced but other morbidity persisted.

Conclusions : A consultation itself is a therapeutic intervention in irritable bowel syndrome with regard to its impact on societal economic burden. It is associated with a durable decrease in illness‐specific health care utilization. It may not address all aspects of irritable bowel syndrome; multiple domains of morbidity demonstrated persistent distress.