bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioactive natural compounds for the treatment of gastrointestinal disorders
Authors: GHOSH Subrata , PLAYFORD Raymond J.
Published: September 2003

Many healthy subjects and patients are taking natural bioactive products for the prevention and treatment of multiple conditions, including gastrointestinal disorders. Based on current evidence, the scientific validity of the use of many of these commercial compounds by the general public is severely limited, with quality control and regulatory issues continuing to be a concern. Nevertheless, there is sufficient preliminary data to warrant further research of these products in order to identify novel compounds for potential clinical use in addition to performing formal randomized controlled clinical trials of the commercial preparations.
Cholecystokinin blockade triggers earlier and enhanced intra-acinar oxygen free radical generation in acute pancreatitis induced by pancreatic duct obstruction in rats
Authors: URUÑUELA Aránzazu , MANSO Manuel A. , DE LA MANO Ana M. , DE DIOS Isabel
Published: September 2003

Cholecystokinin (CCK) has been suggested to be a contributory mediator in acute pancreatitis (AP). The aim of the present study was to assess the role of CCK in the development of oxidative stress at different stages of AP induced by pancreatic duct obstruction (PDO) in rats, using L364,718 (a potent CCK-receptor antagonist) to block CCK action. Intra-acinar oxygen free radical (OFR) generation was analysed by flow cytometry using dihydrorhodamine-123 as a fluorogenic dye. Parallel measurements of pancreatic levels of reduced glutathione (GSH) and of several parameters for the diagnosis of AP were performed in both untreated PDO rats and PDO rats receiving L364,718 (0.1 mg·12 h-1·kg-1). Diagnosis parameters indicated a greater severity of AP in rats treated with the CCK antagonist. The increase in OFR generation observed in acinar cells up to 12 h after inducing AP was triggered at an earlier stages and reached higher values when L364,718 was administered. Accordingly, greater pancreatic GSH depletion was observed in rats with AP treated with the CCK antagonist. Two populations of acinar cells that were differentiated by flow cytometry, R1 and R2, showed similar behaviour with regard to OFR generation in PDO rats; however, R1 cells showed greater sensitivity to L364,718 administration, and thus OFR production was increased in R1 cells earlier than in R2 cells. In conclusion, CCK blockade anticipates and enhances the amount of OFR produced in acinar cells as a consequence of AP, thus leading to earlier development of and more severe disease. The detrimental effect of L364,718 in AP induced by PDO suggests that plasma CCK does not play a major role in the development of this AP model.
Association of maternal and/or fetal factor V Leiden and G20210A prothrombin mutation with HELLP syndrome and intrauterine growth restriction
Authors: SCHLEMBACH Dietmar , BEINDER Ernst , ZINGSEM Juergen , WUNSIEDLER Ute , BECKMANN Matthias W. , FISCHER Thorsten
Published: September 2003

This study was conducted to investigate the association of maternal and/or fetal factor V Leiden (FVL) and G20210A prothrombin mutation with HELLP syndrome. FVL and G20210A prothrombin mutation were determined using PCR. Sixty-three pregnant women, 36 of them diagnosed with HELLP syndrome, were included in the study. Overall, 68 children were born as a result of these pregnancies and blood sampling was possible in 28 out of 39 children from HELLP patients and 25 out of 29 children from the control women. The prevalence of a maternal FVL was elevated 2-fold in HELLP patients compared with the control women [six out of 36 (16.7%) compared with two out of 27 (7.4%); P=0.282]. None of the HELLP patients and only one woman in the control group was found to be positive for the G20210A prothrombin mutation (P=0.251). The fetal carrier frequency was four out of 28 compared with three out of 25 for FVL (P=0.811), and two out of 28 compared with one out of 25 for G20210A prothrombin mutation (P=0.629). Intrauterine growth restriction (IUGR) was significantly higher in fetuses found to be positive for a thrombophilic mutation (P=0.022). IUGR occurred in seven out of ten fetuses with a thrombophilic mutation compared with 11 out of 43 in fetuses without a mutation. The prevalence of FVL, but not of the G20210A prothrombin mutation, seems to be elevated in women with HELLP syndrome. A fetal thrombophilic mutation does not contribute significantly to the clinical features of the HELLP syndrome. Our results demonstrate a fetal contribution to IUGR. Fetal thrombophilic mutations may lead to placental microthrombosis, which consecutively could lead to a disturbed fetoplacental blood flow and thus cause growth restriction.
Effects of euglycaemic and hypoglycaemic hyperinsulinaemia on sympathetic and parasympathetic regulation of haemodynamics in healthy subjects
Authors: LAITINEN Tomi , HUOPIO Hanna , VAUHKONEN Ilkka , CAMARO Cyril , HARTIKAINEN Juha , LAAKSO Markku , NISKANEN Leo
Published: September 2003

The effects of hypoglycaemia during hyperinsulinaemia, occurring under various pathophysiological conditions, on the cardiovascular regulatory system and vasculature are largely unknown. The aim of the present study was to investigate regulatory and haemodynamic responses to acute hyperinsulinaemia and consequent hypoglycaemia in 18 healthy subjects. Blood sampling and 5 min ECG and blood pressure recordings were performed at baseline and during the euglycaemic and hypoglycaemic phases of a hyperinsulinaemic clamp. Heart rate variability (HRV) and blood pressure variability (BPV) were assessed by using power spectral analysis, and baroreflex sensitivity (BRS) was assessed using the cross-spectral method. Stroke volume was assessed from the non-invasive blood pressure signal by the arterial pulse contour method. Euglycaemic hyperinsulinaemia did not change plasma catecholamine concentrations, HRV, BPV, BRS, heart rate, blood pressure, stroke volume, cardiac output or peripheral resistance. However, hyperinsulinaemic hypoglycaemia resulted in an 11.7-fold increase in the plasma adrenaline concentration (from 0.19±0.03 to 1.68±0.32 nmol/l; P<0.001), and a modest 1.3-fold increase in the plasma noradrenaline concentration (from 1.74±0.22 to 2.02±0.19 nmol/l; P<0.05) compared with baseline. Furthermore, we observed significant decreases in diastolic blood pressure (from 68±3 to 60±3 mmHg; P<0.05) and peripheral resistance (from 24.1±1.2 to 18.5±1.1 mmHg·min-1·l-1; P<0.01). Stroke volume and cardiac output increased markedly from the euglycaemic to the hypoglycaemic period only (P<0.01 for both). Hypoglycaemia did not influence HRV, BPV or BRS. Our findings indicate that hyperinsulinaemic hypoglycaemia is characterized by a significant increase in the plasma adrenaline concentration and by decreases in peripheral resistance and blood pressure. Counter-regulation during hyperinsulinaemic hypoglycaemia involves selective adrenomedullary sympathetic activation, and does not influence cardiac parasympathetic regulation or baroreflex control of heart rate.
Sepsis induces the transcription of the glucocorticoid receptor in skeletal muscle cells
Authors: SUN Xiaoyan , MAMMEN Joshua M. V. , TIAN Xintian
Published: September 2003

Evidence from a recent study indicates that glucocorticoids (GCs) mediate skeletal muscle proteolysis during sepsis via the GC receptor (GR) pathway. Attempts to identify the mechanisms regulating GR gene expression in skeletal muscle during sepsis have been hampered by the lack of an appropriate in vitro model system that can mimic in vivo septic conditions. In the present study, we report that GR gene transcription in L6 myocytes in vitro is up-regulated by treatment with sera from septic rats in a manner similar to that measured in septic rats in vivo. Sera from septic rats were collected from animals in which sepsis was induced by caecal ligation and puncture and from control rats that were sham-operated. Finally, by treating L6 myotubes with the GR antagonist RU 38486, thereby preventing sepsis-induced GR transcription, we confirmed that the possible septic effect on the GR was due to increased GCs. L6 myocytes treated with sera from septic rats might therefore be useful as an experimental model for identifying the molecular mechanisms by which the GR regulates muscle cachexia during sepsis. Furthermore, RU 38486 inhibited the sepsis-induced increase in total and myofibrillar energy-dependent protein breakdown rates in incubated extensor digitorum longus muscles from septic and sham-operated rats, as measured by release of tyrosine and 3-methylhistidine respectively. Our results demonstrate for the first time that sepsis induces GR transcription in skeletal muscle, and supports the hypothesis that the GC-induced proteolysis under sepsis is partially a consequence of GR activation.
MHC class I receptors on natural killer cells: on with the old and in with the new
Authors: KHAKOO Salim I. , BROOKS Collin R.
Published: September 2003

The functions of natural killer (NK) cells are controlled by an abundance of activating and inhibitory receptors. Many of these interact with MHC class I molecules. The MHC system also interacts with cytotoxic T-lymphocytes and has been shown to comprise a rapidly evolving family of molecules. This challenges the functional relationship of NK cell receptors with their ligands. Although individual receptors have become subject to species-specific expansions over evolutionary time, the main themes of the NK cell interaction with MHC class I have been preserved. This review details the interaction of NK cell receptors with MHC class I and discusses their unexpectedly rapid evolution.
Differential tissue and enzyme inhibitory effects of the vasopeptidase inhibitor omapatrilat in the rat
Authors: KUBOTA Eiji , DEAN Rachael G. , HUBNER Richard A. , CASLEY David J. , JOHNSTON Colin I. , BURRELL Louise M.
Published: September 2003

Vasopeptidase inhibitors simultaneously inhibit angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The present study characterized the tissue distributions of ACE and NEP, and assessed the effects of the vasopeptidase inhibitor omapatrilat on ACE and NEP in rat tissues. In vivo ACE and NEP inhibition was studied by in vitro autoradiography and using the ACE inhibitor radioligand 125I-MK351A and the NEP inhibitor radioligand 125I-RB104 in rats that received oral omapatrilat (40 mg·day-1·kg-1) for 3 days. In vitro autoradiography was used to examine the distribution of ACE and NEP in the kidney, aorta, heart, adrenal gland, lung, intestine, liver, spleen and brain, and to assess enzyme inhibition after oral omapatrilat. Omapatrilat inhibited plasma ACE and increased plasma renin activity (P<0.01). Tissue ACE was inhibited by 70–95% (P<0.01), except in the brain, where ACE was not inhibited. NEP was inhibited by 87% in the kidney and by 20–40% in atria, aorta, adrenal gland, lung, liver and intestine; it was not inhibited in the brain, the ventricle or the spleen. Omapatrilat is a potent vasopeptidase inhibitor that significantly inhibits tissue ACE and NEP, with the degree of inhibition varying according to the enzyme and the tissue under assessment. The degree and site of tissue enzyme inhibition by vasopeptidase inhibitors may be relevant to end-organ protection as well as to the side-effect profiles of these agents.
Expression and coordinated regulation of matrix metalloproteinases in chronic hepatitis C and hepatitis C virus-induced liver cirrhosis
Authors: LICHTINGHAGEN Ralf , BAHR Matthias J. , WEHMEIER Michael , MICHELS Dirk , HABERKORN Christian I. , ARNDT Burkhard , FLEMMING Peer , MANNS Michael P. , BOEKER Klaus H. W.
Published: September 2003

Matrix metalloproteinases (MMPs) are central to tissue remodelling; however, little is known about the temporal pattern and differential regulation of hepatic MMP expression in the course of chronic human liver disease. Using quantitative reverse transcription–PCR ELISA assays, we studied hepatic mRNA expression of MMP-1, -2, -3, -7, -9, -10, -11, -13 and -14 in patients with chronic hepatitis C and hepatitis C virus-induced end-stage liver cirrhosis and controls. Results were compared with histology, hepatic expression of tissue inhibitor of metalloproteinases (TIMP)-1, -2 and -3, procollagen types I and IV, laminin, and with circulating protein levels of hyaluronate, TIMP-1 and -2 and MMP proenzymes, as measured by ELISA. The impact of the MMP-3(-1171) promoter polymorphism on hepatic MMP-3 expression was analysed. Hepatic mRNA expression data identified differentially regulated groups of MMPs during the course of chronic hepatitis C, showing either steadily increasing mRNA expression with disease progression (MMP-1, -2, -7 and -14) or transiently elevated expression (MMP-9, -11 and -13). The first group closely correlated to the parameters of fibrogenesis. Hepatic MMP-3 expression was unrelated to disease stage, but was determined by the MMP-3(-1171) promoter polymorphism. In conclusion, MMP expression during the course of chronic hepatitis C appears to be a closely regulated process, with different clusters of coordinately regulated MMP genes being identified.
Effect of repetitive exercise testing on breathlessness in humans
Authors: SUBHAN Mirza M. F. , BUTLER Timothy J. , REED James W.
Published: September 2003

There are conflicting reports on the reproducibility of the visual analogue scale (VAS) and the modified Borg scale for the estimation of breathlessness during exercise. In an attempt to clarify the situation, two groups of healthy subjects undertook a progressive exercise test either daily (Group A) or weekly (Group B) on 10 separate occasions. Breathlessness was estimated every 1 min using the VAS. After 10 occasions, both Group A (P<0.05) and Group B (P<0.01) showed a significant increase in the mean intercept of the breathlessness/ventilation (VAS/VI) relationship. The increase was not progressive; using change point regression, reproducible values were found to occur after approximately the fifth occasion in both subject groups. As the slope of the VAS/VI relationship was highly reproducible and did not change with repeat testing, it would appear that at least two mechanisms are involved in the generation of the sensation of breathlessness. A decrease in the exercise heart rate over the same time period was significantly correlated with changes in the VAS/VI intercept in both groups (P<0.01 and P<0.005 respectively). The relationship is unlikely to be causal, but may be indicative of a common underlying mechanism. It is suggested that breathlessness scores are likely to decrease as a direct result of repetitive testing over, on average, the first five periods of assessment. On the basis of this study, it may be inferred that a physiological mechanism contributes to the modulation of breathlessness during repetitive exercise testing.
Effect of maternal obstructive cholestasis during pregnancy on the biliary transport of horseradish peroxidase in the rat offspring
Authors: MONTE Maria J. , VILLANUEVA Gloria R. , MACIAS Rocio I. R. , VAZQUEZ David J. , TOLEDO Marta , DOMINGUEZ Mercedes , MARIN Jose J. G.
Published: September 2003

MOCP (maternal obstructive cholestasis during pregnancy) induces a reversible impairment in bile formation in young rats born to these mothers. The aim of the present study was to gain information on the effects of MOCP on the maturation of pathways involved in protein secretion into bile in young (4-week-old) rats. The amount of hepatic α-tubulin and the structure of the microtubular network were apparently not affected by MOCP. HRP (horseradish peroxidase) was used as a model protein, and its secretion into bile after administration through the jugular vein was measured. In adult (8-week-old) rats, two peaks of HRP output into bile were observed following administration: an early peak presumably due to paracellular transfer, and a late peak presumably due to transcytosis. In young rats (4 weeks old), the early peak was similar to that of adult animals, and was not affected by MOCP. However, the late peak was markedly smaller in young control rats, and was further reduced by MOCP. Brefeldin A decreased, whereas taurocholate did not change, the early peak, whereas both affected the transcytotic transport of HRP. Brefeldin A delayed HRP secretion (similarly in control and MOCP groups), without affecting cumulative output, whereas taurocholate accelerated the transcytotic transport of HRP in the control group, but not in the MOCP group. These results suggest that MOCP affects the maturation of hepatocyte mechanisms involved in the transcytotic secretion of HRP into bile.
Fetuin/α2-HS glycoprotein enhances phagocytosis of apoptotic cells and macropinocytosis by human macrophages
Authors: JERSMANN Hubertus P. A. , DRANSFIELD Ian , HART Simon P.
Published: September 2003

Inflammatory diseases are associated with reduced serum concentrations of α2-HS glycoprotein (the human homologue of bovine fetuin), but the role of fetuin in inflammation is poorly understood. We hypothesized that fetuin may influence the resolution of inflammation by modulating the phagocytosis of apoptotic cells by macrophages. Using an in vitro flow cytometry-based phagocytosis assay, we investigated the role of fetuin in apoptotic cell clearance. Bovine fetuin and human α2-HS glycoprotein significantly augmented the phagocytosis of apoptotic cells by human peripheral blood monocyte-derived macrophages, whereas the control proteins BSA, sialylated BSA and asialofetuin were ineffective. The enhancement of phagocytosis was concentration-dependent, and required the presence of intact fetuin at the time of interaction between macrophages and apoptotic cells. Fetuin also substantially increased the uptake of labelled dextran 70000 by macrophages, which occurs by macropinocytosis, suggesting that this may be one of the mechanisms utilized for apoptotic cell uptake.
Statins and their role in vascular protection
Authors: MASON Justin C.
Published: September 2003

The statins reduce cholesterol synthesis through inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase and are widely prescribed for hyperlipidaemia to reduce the risk of atherosclerotic complications. The beneficial effect of lipid lowering by statins in the treatment of coronary heart disease has been demonstrated in large clinical trials. However, statins appear to have additional benefits on vascular function above and beyond their lipid lowering effects. Through inhibition of L-mevalonate synthesis, statins also prevent the synthesis of isoprenoid intermediates, including farnesylpyrophosphate and geranylgeranylpyrophosphate. Isoprenylation is important in the post-translational modification of a variety of proteins, including the small GTPases Rho, Rac and Ras, and hence plays an integral role in cellular signalling. Moreover, interference with isoprenylation underlies many of the beneficial actions of the statins on vascular endothelium, which include increased endothelial nitric oxide synthase expression, pro-angiogenic effects, increased fibrinolytic activity, immunomodulatory and anti-inflammatory actions, including increased resistance to complement. This has led to interest in the use of this class of drugs outside the realm of cardiovascular disease.
A physiological role for α2-HS glycoprotein: stimulation of macrophage uptake of apoptotic cells
Authors: LORD Janet M.
Published: September 2003

This comment describes the study by Jersmann and co-workers in this issue of Clinical Science reporting the results of a study of the role of the serum glycoprotein fetuin in the uptake of apoptotic cells by macrophages. They show that fetuin is able to stimulate the macropinocytosis of apoptotic cells in vivo, which would be therapeutically useful following chemotherapy when the increased numbers of apoptotic cells could exceed the capacity of the macrophage network.
Aetiology of pre-eclampsia and thrombophilic genetic mutations
Authors: HAYASHI M.
Published: September 2003

Schlembach and co-workers in this issue of Clinical Science have studied the association of maternal and/or fetal factor V Leiden (FVL) and prothrombin G20210A gene mutation with HELLP syndrome and intrauterine growth restriction (IUGR) to confirm whether these genetic mutations are important risk factors for the pathogenesis of the HELLP syndrome, leading to an inadequate maternal–fetal circulation. Results showed that fetal FVL and prothrombin G20210A gene mutation were significantly associated with IUGR. The authors speculated that fetal thrombophilic mutations resulted in placental microthrombosis, leading to a disturbed fetoplacental blood flow. This study represents another important step in our understanding of the pathophysiological action of fetal thrombophilic mutations on fetal development. Regarding the aetiology of pre-eclampsia, one possible speculation is that systemic immune maladaptation, including systemic cytokine imbalance, contributes to placental ischaemia and systemic vessel abnormalities leading to pre-eclampsia.
Perinatal Malnutrition Programs Sympathoadrenal and Hypothalamic‐Pituitary‐Adrenal Axis Responsiveness to Restraint Stress in Adult Male Rats
Authors: Lesage J. , Dufourny L. , Laborie C. , Bernet F. , Blondeau B. , Avril I. , Bréant B. , Dupouy J. P.
Published: September 2003

In humans, an altered control of cortisol secretion was reported in adult men born with a low birth weight making the hypothalamic‐pituitary‐adrenal (HPA) axis a possible primary target of early life programming. In rats, we have recently shown that maternal food restriction during late pregnancy induces both an intrauterine growth retardation and an overexposure of fetuses to maternal corticosterone, which disturb the development of the HPA axis in offspring. The first aim of this work was to investigate, in adult male rats, whether perinatal malnutrition has long‐lasting effects on the HPA axis activity during both basal and stressful conditions. Moreover, as the HPA axis and sympathetic nervous system are both activated by stress, the second aim of this work was to investigate, in these rats, the adrenomedullary catecholaminergic system under basal and stressful conditions. This study was conducted on 4‐month‐old male rats malnourished during their perinatal life and on age‐matched control animals. Under basal conditions, perinatal malnutrition reduced body weight and plasma corticosteroid‐binding globulin (CBG) level but increased mineralocorticoid receptor (MR) gene expression in CA1 hippocampal area. After 30 min of restraint, perinatally malnourished (PM) rats showed increased plasma noradrenaline, adrenocorticotropin hormone (ACTH) and corticosterone concentrations similarly as controls, but calculated plasma‐free corticosterone concentration was significantly higher and adrenaline level lower than controls. During the phase of recovery, PM rats showed a rapid return of plasma ACTH and corticosterone concentrations to baseline levels in comparison with controls. These data suggest that in PM rats, an elevation of basal concentrations of corticosterone, in face of reduced CBG and probably increased hippocampal MR lead to a much larger impact of corticosterone on target cells that mediate the negative‐feedback mechanism on the activities of both the HPA axis and sympathoadrenal one.
Cardiac scoring systems – what is their value?
Authors: Ridley S.
Published: September 2003

Estimating the peri‐operative risk of major adverse cardiac events is one of the functions of cardiac risk scoring systems. Fortunately, peri‐operative cardiac complications are relatively infrequent in most patients. Clinical algorithms use sequential screening tests to detect patients most at risk of cardiac complications. However, because the sensitivity and specificity of the tests used are low, the predictive performance of the commonly‐used cardiac screening tests may not be completely satisfactory. The purpose of this review is to describe measures of performance of cardiac screening tests and illustrate their potential benefits and weaknesses.
A new mirrored laryngoscope*
Authors: McMorrow R. C. N. , Mirakhur R. K.
Published: September 2003

A new laryngoscope has been designed, incorporating an adjustable mirror and a levered tip similar to the McCoy blade, in an attempt to bridge the gulf between simple direct laryngoscopy and fiberoptic laryngoscopy. Manual in‐line neck stabilisation was used to simulate difficult laryngoscopy in 14 anaesthetised patients after full neuromuscular blockade. The best view at laryngoscopy was assessed using a standard Macintosh laryngsocope, a size 3 McCoy laryngoscope and the mirrored laryngoscope. The best laryngeal view obtained in all cases with the Macintosh blade was a grade 3. The mirrored laryngoscope improved this view in 10 cases (71%) compared with five cases (36%) with the McCoy laryngoscope (p = 0.005); in seven cases (50%), the view improved to a grade 1 compared with no cases when the McCoy was used (p = 0.02). We conclude that the mirrored laryngoscope offers considerable advantages over the Macintosh and the McCoy laryngoscopes in simulated difficult laryngoscopy, is simple to use and requires no special training.
Pharmacokinetics of sevoflurane uptake into the brain and body
Authors: Lu C. C. , Tsai C. S. , Ho S. T. , Chen W. Y. , Wong C. S. , Wang J. J. , Hu O. Y. P. , Lin C. Y.
Published: September 2003

The aim of this study was to investigate the pharmacokinetics of sevoflurane uptake into the brain and body by comparing sevoflurane concentrations in internal jugular‐bulb blood (Jsev), arterial blood (Asev) and pulmonary arterial blood (PAsev) over a fixed inspired sevoflurane concentration. Ten patients (aged 51–73 years), undergoing coronary artery bypass grafting surgery were enrolled in this study. They were anaesthetised using a constant 3.5% inspired sevoflurane concentration (CIsev) during the first hour of anaesthesia. During constant volume‐controlled ventilation, we measured CIsev and end‐tidal sevoflurane (CEsev) using infrared analysis. The sevoflurane concentration in the blood was analysed using gas chromatography, and cardiac output was measured using an Opti‐Q pulmonary artery catheter. We found that it took 40 min for the brain concentration to equilibrate with arterial blood (Asev). Both CIsev–CEsev and Asev–PAsev gradients persisted during the study period. There was no further uptake of sevoflurane into the brain after 40 min; however, there was near‐constant uptake into the body.
Assessing the learning needs of college tutors in anaesthesia: proposals for an introductory learning package*
Authors: Edgar J. , Glavin R.
Published: September 2003

At present there is no nationwide formal training course at which college tutors in anaesthesia can develop the specific skills required to perform their important role effectively. The purpose of this study was to ascertain whether there is a need for an introductory learning package for college tutors and if so, what learning needs ought to be addressed in such a package. A needs assessment was performed involving the use of individual interviews and the administration of two sequential questionnaires. The questionnaire was completed by 208 college tutors, a return rate of 83%. Most college tutors (93%) said they had had no formal training to perform their role and 94% felt there was a need for an introductory course for college tutors in anaesthesia. Of those, 77% said they would be interested in taking such a course. The study identified a number of learning needs.
Intragastric pressure and its relevance to protective cricoid force*
Authors: Haslam N. , Syndercombe A. , Zimmer C. R. , Edmondson L. , Duggan J. E.
Published: September 2003

Cricoid pressure is frequently used to protect the anaesthetised and paralysed patient from passive regurgitation. Although intragastric pressure (Pga) drives regurgitation, its relevance in the setting of protective cricoid force has been largely ignored. We sought to define the likely range of Pga encountered in the population at risk. We studied 100 consecutive patients presenting for surgery requiring mechanical ventilation. We measured respiratory swings in Pga during mechanical ventilation in the paralysed state following rapid sequence induction (n = 24) and routine induction of anaesthesia (n = 76). Pga (mmHg) in the whole group recorded at end‐inspiration (Pga‐In) and end‐expiration (Pga‐Ex) was [mean (SD)]: Pga‐In 6.48 (2.60) mmHg and Pga‐Ex 3.23 (2.24) mmHg. We found no correlation between Pga and body mass index (r2 = 0.018). These findings have implications for the level of cricoid force required to protect a patient during the induction of anaesthesia.
Assessment of the effect upon maternal knowledge of an information leaflet about pain relief in labour*
Authors: Stewart A. , Sodhi V. , Harper N. , Yentis S. M.
Published: September 2003

Pregnant women were randomly assigned to receive, at booking, the usual written information pack either with or without the Obstetric Anaesthetists' Association's (OAA's) leaflet ‘Pain Relief in Labour’. At 36 weeks' gestation, a structured interview was conducted at which we assessed the sources of information the women had used and their knowledge of specific aspects of obstetric analgesia and anaesthesia described in the OAA leaflet. The most useful sources of information overall were friends, family, midwives, books and information leaflets (no significant difference between the groups); 72% of all women felt they had received adequate information although 70% said they would have liked to have discussed methods of analgesia with an anaesthetist before delivery. Parturients allocated to receive the leaflet (n = 37) were more knowledgeable than those who received only standard booking information (n = 39) about all analgesic and anaesthetic techniques except for systemic pethidine, although this difference in knowledge only reached statistical significance for extending epidural analgesia for emergency Caesarean section. We conclude that the OAA leaflet improves women's knowledge of analgesic techniques and suggest that all information of this type be formally assessed in this manner; furthermore given the practical difficulties in conducting studies of this type, the latter should be adequately resourced, perhaps by the bodies that issue such leaflets.
Recent trends in tracheal intubation: a retrospective analysis of 97 904 cases
Authors: Yarrow S. , Hare J. , Robinson K. N.
Published: September 2003

We conducted a review of routine anaesthetic audit data collected between April 1995 and December 2001 at Northampton General Hospital. A total of 97 904 anaesthetics were given. The average monthly rate of tracheal intubation fell during the study period from ∼450 per month to ∼280 per month. This was largely at the expense of tracheal tubes used during normal working hours, which fell by 40% (from ∼390 per month to ∼230 per month). Use outside normal working hours did not change. Of those cases managed in normal working hours with a tracheal tube, the decline in use over time was most obvious in patients of ASA physical status 1–2, and whose surgery was classified as elective or scheduled. The proportion of cases classified as ASA 3–5 or whose surgery was urgent or emergency increased (from 15.5% to 22.3%, and from 7.5% to 15.5%, respectively.) There was considerable variation across surgical specialities, with the greatest decline in tracheal intubation in head and neck surgery. These changes in practice have implications for the teaching of airway management skills.
Sacrococcygeal local anaesthesia versus general anaesthesia for pilonidal sinus surgery: a prospective randomised trial
Authors: Naja M. Z. , Ziade M. F. , El Rajab M.
Published: September 2003

Sixty patients scheduled for pilonidal sinus surgery were prospectively randomly assigned to receive general anaesthesia or sacrococcygeal local anaesthesia with a newly‐described technique. Patients in the general anaesthesia group spent more time in the operating theatre and recovery room than did those in the local anaesthesia group (p < 0.05). Two thirds (67%) of the patients in the local anaesthesia group left hospital on the day of surgery compared to only 17% of patients in the general anaesthesia group (p < 0.05). Visual analogue scale pain scores performed during the 3‐day follow‐up period favoured the local anaesthetic technique (p < 0.05). Postoperative analgesia requirements were greater in the general anaesthesia group than in the local anaesthesia group (p < 0.05). The majority of patients and surgeons expressed satisfaction with local anaesthesia. Sacrococcygeal local anaesthesia appears to be a successful alternative to general anaesthesia for pilonidal sinus surgery.
Conservation ethics and anaesthesia
Authors: Houghton I. T.
Published: September 2003

The current attitude of conservators towards restoration is to preserve objects and materials in the condition as they are but without attempting to restore them ‘as new’. Museum objects have generally ceased to serve their original utilitarian function but have become objects for study, information and inspiration. Conservation and restoration are discussed in relation to anaesthetic exhibits. Conservation is the prevention, detection, containment, control and recovery but risk avoidance and monitoring hopefully will lessen the need for conservation. Some objects such as rubber and plastic items are, by their very nature, prone to ageing, accident and mistreatment. Cleaning and maintenance may lead to loss of original detail and is ‘an act of critical interpretation’. Reshaping of distorted objects and repair of broken pieces can sometimes be justified but, in other work, the actual restoration may become part of the object's history that should not be lost in trying to restore something to a presumed earlier state. The mind interprets images by reference to earlier patterns and so imperfections, if not disguised, may be unduly distracting. Museums exist for information, evidence, enlightenment and even entertainment. Conservation must serve these purposes and is not an end in its own right. The professional actions of the conservator must be governed by a total respect for physical, historic, and aesthetic integrity but this must be interpreted widely.
A comparison of bispectral index and ARX‐derived auditory evoked potential index in measuring the clinical interaction between ketamine and propofol anaesthesia
Authors: Vereecke H. E. M. , Struys M. M. R. F. , Mortier E. P.
Published: September 2003

We evaluated the effects of a bolus (0.4 mg.kg−1) and continuous infusion (1 mg.kg−1.h−1) of ketamine on Bispectral Index (BIS) and A‐Line® ARX Index (AAI) during propofol anaesthesia. We included 15 ASA I patients scheduled for general anaesthesia. Induction was performed by infusion of propofol at 100 ml.h−1 until loss of consciousness. Both BIS and AAI monitors responded appropriately at that time. The calculated effect site concentration of propofol at loss of consciousness was maintained by means of a computer controlled infusion system. A ‘pseudo’ steady‐state effect site concentration was reached after 4 min. After 1 min of baseline measurements, ketamine was administered. BIS values increased from the 3rd to the 8th min after the administration of ketamine. The AAI showed no significant increase or decrease, but between‐patient variability increased.
Consent and anaesthetic risk
Authors: Jenkins K. , Baker A B.
Published: September 2003

The incidences of mortality and morbidity associated with anaesthesia were reviewed. Most of the published incidences for common complications of anaesthesia vary considerably. Where possible, a realistic estimate of the incidence of each morbidity has been made, based on the best available data. Perception of risk and communication of anaesthetic risk to patients are discussed. The incidences of anaesthetic complications are compared with the relative risks of everyday events, using a community cluster logarithmic scale, in order to place the risks in perspective when compared with other complications and with the inherent risks of surgery. Documentation of these risks and discussion with patients should allow them to be better informed of the relative risks of anaesthetic complications. Depending on specific comorbidities and the severity of operation, these risks associated with anaesthesia may increase for any one individual.
Hyperbaric oxygen inhibits stimulus-induced proinflammatory cytokine synthesis by human blood-derived monocyte-macrophages
Authors: Benson R M , Minter L M , Osborne B A , Granowitz E V
Published: September 2003

Hyperbaric oxygen (HBO) is 100% oxygen administered at elevated atmospheric pressure to patients with inflammatory diseases. We developed an in vitro model to investigate the effects of HBO on stimulus-induced proinflammatory cytokine transcription and translation. Human blood-derived monocyte-macrophages were stimulated before being transferred to an HBO chamber where they were incubated at 97·9% O2, 2·1% CO2, 2·4 atmospheres absolute, 37°C. Controls were maintained in the same warm room at normoxia at sea level, hyperoxia or increased pressure alone. A 90-min HBO exposure inhibited IL-1β synthesized in response to lipopolysaccharide by 23%, lipid A by 45%, phytohaemagglutinin A (PHA) by 68%, and tumour necrosis factor (TNF)-α by 27%. HBO suppressed lipopolysaccharide-, lipid A- and PHA-induced TNF-α by 29%, 31% and 62%, respectively. HBO transiently reduced PHA-induced steady state IL-1β mRNA levels. Hyperoxia alone and pressure alone did not affect cytokine production. The immunosuppressive effect of HBO was no longer evident in monocyte-macrophages exposed to HBO for more than 3 h. Interestingly, cells exposed to HBO for 12 h synthesized more IL-1β than cells cultured under control conditions. In summary, HBO exposure transiently suppresses stimulus-induced proinflammatory cytokine production and steady state RNA levels.
TGF-β1 production in inflammatory bowel disease: differing production patterns in Crohn's disease and ulcerative colitis
Authors: DEL ZOTTO B , MUMOLO G , PRONIO A M , MONTESANI C , TERSIGNI R , BOIRIVANT M
Published: September 2003

Transforming growth factor-β (TGF-β) is an inhibitory cytokine recognized as a key regulator of immunological homeostasis and inflammatory responses. TGF-β is involved in experimental models of oral tolerance and in the pathogenesis of experimental colitis. Patients with inflammatory bowel disease (IBD) have inappropriate T cell responses to antigenic components of their own intestinal microflora, suggesting the presence of a disorder in the normal mucosal immune mechanism that ensures the down-regulation of responses to harmless constituents in the microflora. To evaluate the contribution of TGF-β to this imbalance, we measured TGF-β1 production by lamina propria mononuclear cells (LPMC) and T cells isolated from tissue specimens of patients with Crohn's disease (CD), ulcerative colitis (UC) and controls. Cells were cultured in the presence or absence of anti-CD2 plus anti-CD28 MoAbs and TGF-β1 production in culture supernatants was measured by ELISA. LPMC isolated from CD patients produced significantly less TGF-β1 than controls when stimulated via CD2 plus CD28 pathways (P = 0·001)] conversely, in UC patients increased production of TGF-β1 compared to controls was observed (P = 0·0005). These differences were also observed with purified lamina propria (LP) T cells in both diseases and were associated with the presence of inflammation. Thus, TGF-β1 production shows contrasting secretion in CD and in UC, probably as a consequence of the different Th polarization. The absolute or relative defect in TGF-β1 production observed in CD and UC may contribute to the perpetuation of inflammation.
Delivery of antigen in allogeneic cells preferentially generates CD4+ Th1 cells
Authors: AGREWALA J N , SUVAS S , SINGH V , VOHRA H
Published: September 2003

We have examined the possibility of evoking antigen-specific T cell immune response by using allogeneic cells as a source of adjuvant and also as a vehicle to deliver antigen. The mice were immunized with different preparations of antigen-pulsed allogeneic and syngeneic splenocytes. It was observed during the study that the animals immunized with antigen-pulsed mitomycin C treated allogeneic cells elicited antigen specific CD4+ Th1 cell response. Predominant release of IL-2, interferon (IFN)-γ and IgG2a-isotype also occurred. In contrast, mice immunized with antigen-pulsed syngeneic cells chiefly enhanced the production of interleukin (IL)-4 and IgG1-isotype. Further, allogeneic macrophages induced better T cell response than B cells or splenocytes and prominently induced the expression of B7-1 and B7-2. Immunization with antigen-pulsed macrophages provided better recall responses compared to B cells. This was manifested by the high LFA-1α and low CD45RB expression on T cells. Because it is already known that mitomycin C-treated cells undergo apoptosis and dendritic cells engulf apoptotic cells, we therefore propose that generation of T cell response using antigen-pulsed allogeneic cells may be due to the engulfment of these cells by dendritic cells, which may then process and present antigen entrapped in allogeneic cells to activate naive CD4+ T cells and differentiate them to Th1 cells. This study therefore provides a rational basis for manipulating antigen-specific responses by immunizing with antigen-pulsed allogeneic cells.
Circulating adiponectin levels during human endotoxaemia
Authors: KELLER P , MØLLER K , KRABBE K S , PEDERSEN B K
Published: September 2003

Adiponectin, an adipocytokine secreted by fat tissue, may prevent development of diabetes type II, as high adiponectin levels are linked with insulin sensitivity. In contrast, tumour necrosis factor (TNF)-α, which is also produced by fat tissue, leads to insulin resistance and furthermore inhibits adiponectin mRNA production and secretion of the protein. However, adiponectin also negatively regulates TNF-α levels. Therefore, we set out to test whether an infusion of endotoxin would influence circulating adiponectin levels in healthy human subjects. Twenty-three healthy human subjects were injected with endotoxin (2 ng/kg body weight); eight of these subjects were also injected with saline and served as controls. Plasma levels of adiponectin, TNF-α and interleukin-6 were measured at 0, 1·5, 2, 4, 8 and 24 h. TNF-α and interleukin-6 levels peaked at 1·5 h and 2 h, respectively. Control subjects injected with saline showed a decrease in adiponectin plasma levels with time (P < 0·05) presumably owing to the effect of fasting or physical inactivity. However, there was no change in adiponectin plasma levels in endotoxin injected subjects, thus the effect of fasting was opposed. In conclusion, circulating adiponectin levels are reduced during a resting and fasting state, an effect reversed by endotoxin injection.
Dnase1l3 deficiency in lupus-prone MRL and NZB/W F1 mice
Authors: WILBER A , O'CONNOR T P , LU M L , KARIMI A , SCHNEIDER M C
Published: September 2003

Loss of deoxyribonuclease I (Dnase1) function is associated with systemic lupus erythematosus (SLE) in humans and mice; however, no coding mutations in Dnase1 are found in polygenic murine models. Instead, both MRL-lpr strains and NZB/W F1 hybrids are homozygous for T89I missense in the macrophage-DNASE, desoxyribonuclease I-like 3 (Dnase1l3). By in vitro expression studies, this substitution decreases this enzyme's nuclease activity against free DNA by only approximately twofold; however, the mutation has a greater effect on the capacity of media conditioned with Dnase1l3 to confer a barrier to liposomal gene transfection to HeLa cells. The 89I substitution decreases the Dnase1l3 barrier function in vitro by eightfold (P < 0·01). In splenocytes and BM-derived macrophages of SLE mice, while cellular Dnase1l3 levels are induced relative to C57BL/6 (control) mice, levels of FD-nuclease activity are similar. Finally, media conditioned by MRL and NZB/W F1 macrophages, relative to control, contains a weak interferon-gamma (IFN-γ) inducible Dnase1l3-associated barrier to transfection. This barrier function is hypothesized to reflect the inability of SLE mice to degrade membrane-enveloped DNA-associated antigens, such as apoptotic bodies, which are predicted to stimulate the characteristic autoimmunity of SLE. Our results for these two generally independent models strongly suggest that Dnase1l3 deficiency increases the susceptibility of these mice to polygenic SLE.
Over-expression of interleukin 10 in mucosal T cells of patients with active ulcerative colitis
Authors: MELGAR S , YEUNG M M-W , BAS A , FORSBERG G , SUHR O , ÖBERG Å , HAMMARSTRÖM S , DANIELSSON Å , HAMMARSTRÖM M-L
Published: September 2003

Ulcerative colitis (UC), a chronic inflammatory bowel disease, exhibits pronounced increase of T lymphocytes in the inflamed mucosa. To understand the role of intestinal T lymphocytes in the pathogenesis of UC their cytokine production in the mucosa was analysed. Intestinal T lymphocytes of UC, Crohn's disease and control patients were analysed for cytokine mRNA levels by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) directly after isolation without in vitro stimulation. Frequencies of cytokine positive cells were determined in UC and control colon by immunomorphometry. T lymphocytes in normal colon expressed interleukin (IL)-2, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and transforming growth factor (TGF)-β1, but not IL-4, IL-5 or IL-10. In UC, a highly significant increase in IL-10 mRNA levels in T lymphocytes and an increased frequency of IL-10 positive cells was seen in colon. IL-10 mRNA levels were also elevated in T lymphocytes of the non-inflamed ileum and correlated with disease activity at both locations. CD4+ T lymphocytes were the major source of IL-10 mRNA. IL-2, IFN-γ and TNF-α mRNA levels were decreased in colonic T lymphocytes, and virtually no IL-2, IFN-γ, TNF-α or TGF-β positive cells were detected in basal lymphoid aggregates. However, scattered IL-10 positive cells were found here. Lamina propria outside the aggregates contained IL-10-, IFN-γ, TNF-α and TGF-β but not IL-2 positive cells. T cells of UC patients did not express IL-4 or IL-5. Taken, together the data suggest a generalized activation of IL-10 producing CD4+ T cells along the intestine of UC patients. The local environment seems to determine the biological consequences of elevated IL-10.
Biclonal expansion of T cells infected with monoclonal Epstein–Barr virus (EBV) in a patient with chronic, active EBV infection
Authors: TOYABE S , HARADA W , UCHIYAMA M
Published: September 2003

Recent studies have suggested that a high percentage of Epstein–Barr virus (EBV)-infected lymphocytes in peripheral blood of patients with chronic, active EBV infection (CAEBV) is of T cell origin. Although T cells are expanded oligoclonally in CAEBV, it is not clear whether the restricted diversity of T cells arise from immune reaction against EBV-related antigens or from proliferation of EBV-infected cells. We experienced a patient with CAEBV who had biclonal expansion of peripheral blood T cells. We identified clonotypes of these two T cell clones in detail and purified the T cell clones. EBV infected mainly the two T cell clones, whereas the viral loads in peripheral blood cells other than these T cell clones were low or undetectable. The EBV strains infecting the two T cells clones were indistinguishable from each other by a series of genotype analyses of the virus. These results suggest that the two T cell clones infected with the same monoclonal EBV proliferated in peripheral blood of the patient.