bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic structure of Mycosphaerella fijiensis populations from Australia, Papua New Guinea and the Pacific Islands
Authors: Hayden H. L. , Carlier J. , E. A. B. Aitken
Published: December 2003

Single‐copy restriction fragment length polymorphism (RFLP) markers were used to determine the genetic structure of Mycosphaerella fijiensis, the cause of black leaf streak (black Sigatoka) disease of banana and plantain, in the Torres Strait, Papua New Guinea (PNG), and the Pacific Islands. A moderate level of genetic variation was observed in all populations with genotypic diversity values of 60–78% of the theoretical maximum, and gene diversity (H) values between 0·269 and 0·336. All populations were at gametic equilibrium, and with the high level of genotypic diversity observed this indicated that sexual reproduction has a major role in the genetic structure of the M. fijiensis populations examined. Population differentiation was tested on several hierarchical scales. No evidence of population differentiation was observed between sites on Mer Island. A moderate level of population differentiation was observed within the Torres Strait, between Badu and Mer Islands (FST = 0·097). On a regional scale, the greatest differentiation was found between the populations of the Torres Strait and the Pacific. Populations from these regions were more closely related to the PNG population than to each other, suggesting they were founded in separate events from the same population.
Phytophthora species in oak ecosystems in Turkey and their association with declining oak trees
Authors: Balcì Y. , Halmschlager E.
Published: December 2003

From 1999 to 2001, a survey on the occurrence of Phytophthora spp. in the rhizosphere soil of healthy and declining oak trees was conducted in 51 oak stands in Turkey. Seven Phytophthora spp. were recovered from six out of the nine oak species sampled: P. cinnamomi, P. citricola, P. cryptogea, P. gonapodyides, P. quercina, Phytophthora sp. 1 and Phytophthora sp. 2. The most frequently isolated species, P. quercina, was very common on slopes susceptible to drought. It occurred in four different climatic zones and on six Quercus spp., suggesting that it is native to oaks. The second most common species, P. citricola, was separated into three subgroups: type C was recovered only in Anatolia, whereas A and B occurred only in the European part of Turkey. Phytophthora cinnamomi was recovered at one site only, and may not be involved in oak decline in Turkey. The other four species were recovered sporadically. On affected sites there was a significant association between deteriorating crown status and the presence of Phytophthora spp., particularly P. quercina. The occurrence of Phytophthora species was significantly influenced by soil pH. Stem inoculation tests on oak seedlings revealed that Q. petraea was the most susceptible species.
Variation in susceptibility to pitch canker disease, caused byFusarium circinatum, in native stands ofPinus muricata
Authors: Schmale D. G. , Gordon T. R.
Published: December 2003

Two hundredPinus muricatatrees, located within a native forest near Monterey, California, were inoculated with the pitch canker pathogen. Treated branches were removed 10–13 weeks following the initial inoculation, and the lengths of the lesions that developed at each of the inoculation sites were measured. Results indicated that bishop pine exhibits a wide range of variation in susceptibility to pitch canker disease. Of the trees that received only one inoculation, 27% showed almost no lesion development, indicating that they were relatively resistant to the pathogen, while others had significantly longer lesions and thus were more susceptible. Clonal propagation and seed collection from resistant individuals may offer useful strategies for disease management in the future.
Development of a recombinant antibody ELISA test for the detection ofPolymyxa betaeand its use in resistance screening
Authors: Kingsnorth C. S. , Asher M. J. C. , Keane G. J. P. , Chwarszczynska D. M. , Luterbacher M. C. , . Mutasa‐Göttgens E. S
Published: December 2003

An ELISA test was developed for the quantitative detection of the obligate parasitePolymyxa betae, the vector ofBeet necrotic yellow vein virus(BNYVV), in infected sugarbeet roots. The test used monoclonal and polyclonal antibodies raised to a recombinantly expressed glutathione‐S‐transferase (GST) fromP. betae. A close correlation was found between the number ofP. betaezoospores in serially diluted suspensions and absorbance values in the ELISA test. Time‐course studies of plants grown in naturally infested soils in controlled environment tests demonstrated the value of the ELISA test in screening forP. betaeresistance. In preliminary tests,P. betae‐resistant accessions of the wild sea beet (Beta vulgarisssp.maritima), which might be used to restrict the transmission of BNYVV, were identified.
Rapid detection of Phytophthora cinnamomi using PCR with primers derived from the Lpv putative storage protein genes
Authors: Kong P. , Hong C. X. , Richardson P. A.
Published: December 2003

Phytophthora cinnamomi is an ecologically and economically important pathogen. In this study, PCR assays were developed with primer pair LPV2 or LPV3 for rapid detection and identification of this organism. Both primer pairs were selected from putative storage protein genes. The specificity of these primer pairs was evaluated against 49 isolates of P. cinnamomi, 102 isolates from 30 other Phytophthora spp., 17 isolates from nine Pythium spp. and 43 isolates of other water moulds, bacteria and true fungi. PCR with both primer pairs amplified the DNA from all isolates of P. cinnamomi regardless of origin. The LPV3 primers showed adequate specificity among all other species tested. The LPV2 primers cross‐reacted with some species of Pythium and true fungi, but not with any other Phytophthora species. PCR with the LPV3 primers detected the pathogen at levels of a single chlamydospore or 10 zoospores in repeated tests. The PCR assay was at least 10 times more sensitive than the plating method for detection of the pathogen from artificially infested soilless medium, and, to a lesser extent, from naturally infected plants. PCR with LPV3 primers can be a useful tool for detecting P. cinnamomi from soilless media and plant tissues at ornamental nurseries, whereas the LPV2 primers can be an effective alternative for identification of this species from pure culture. Applications of these assays for detection of P. cinnamomi in other environments were also discussed.
Age‐related effects in the EEG during propofol anaesthesia
Authors: Schultz A. , Grouven U. , Zander I. , Beger F. A. , Siedenberg M. , Schultz B.
Published: December 2003

Background:  Age‐related differences in the spectral composition of the EEG in induction and emergence times, and in drug consumption during propofol anaesthesia were investigated.

Methods:  The EEGs of 60 female patients between 22 and 85 years of age were monitored continuously during standardized induction of anaesthesia with 2 mg of propofol kg−160 s−1. The EEGs were visually assessed in 20‐s epochs according to a scale from A (awake) to F (very deep hypnosis). Visual EEG classifications, spectral parameters, and induction times were compared between different age groups. Additionally, data of 546 patients included in a multicentre study with 4630 patients (EEG monitor Narcotrend®, MT MonitorTechnik, Bad Bramstedt, Germany) were analyzed with regard to age‐dependent changes of propofol consumption using target‐controlled infusion (TCI).

Results:  During induction, patients older than 70 years reached significantly deeper EEG stages than younger patients, needed a longer time to reach the deepest EEG stage, and needed more time until a light EEG stage was regained. In patients aged 70 years and older, the total power, mainly in deep EEG stages, was significantly smaller due to a distinctly smaller absolute power of the delta frequency band. No single spectral parameter was able to reliably distinguish all EEG stages.

During the steady state of anaesthesia, older patients needed less propofol for the maintenance of a defined stage of hypnosis than younger patients.

Conclusion:  Older patients differ from younger ones regarding the hypnotic effect of propofol and the spectral patterns in the EEG. For an efficient automatic assessment of the EEG during anaesthesia a multivariable approach accounting for age‐effects is indispensable.
Reduction in the incidence of awareness using BIS monitoring
Authors: Ekman A. , Lindholm M‐L. , Lennmarken C. , Sandin R.
Published: December 2003

Background:  Explicit recall (ER) is evident in approximately 0.2% of patients given general anaesthesia including muscle relaxants. This prospective study was performed to evaluate if cerebral monitoring using BIS to guide the conduction of anaesthesia could reduce this incidence significantly.

Patients and methods:  A prospective cohort of 4945 consecutive surgical patients requiring muscle relaxants and/or intubation were monitored with BIS and subsequently interviewed for ER on three occasions. BIS values between 40 and 60 were recommended. The results from the BIS‐monitored group of patients was compared with a historical group of 7826 similar cases in a previous study when no cerebral monitoring was used.

Results:  Two patients in the BIS‐monitored group, 0.04%, had ER as compared with 0.18% in the control group (P < 0.038). Both BIS‐monitored patients with ER were aware during intubation when they had high BIS values (>60) for 4 min and more than 10 min, respectively. However, periods with high BIS = 4 min were also evident in other patients with no ER. Episodes with high BIS, 4 min or more, were found in 19% of the monitored patients during induction, and in 8% of cases during maintenance.

Conclusions:  The use of BIS monitoring during general anaesthesia requiring endotracheal intubation and/or muscle relaxants was associated with a significantly reduced incidence of awareness as compared with a historical control population.
Pulmonary inflammatory mediators after sevoflurane and thiopentone anaesthesia in pigs
Authors: Takala R. S. K. , Soukka H. R. , Salo M. S. , Kirvelä O. A. , Kääpä P. O. , Rajamäki A. A. , Riutta A. , Aantaa R. E.
Published: December 2003

Background:  Volatile anaesthetics have been shown to affect the release of pulmonary inflammatory mediators and exacerbate pulmonary injury after experimental aspiration. Thus, in theory, volatile anaesthetics may worsen inflammatory pulmonary injury and disease. We have previously described that no significant changes in alveolar ultrastructure are seen after sevoflurane anaesthesia. However, this does not exclude any possible physiological alterations. The aim of our study was to evaluate pulmonary inflammatory mediators in bronchoalveolar lavage (BAL) after sevoflurane and thiopentone anaesthesia in pigs with intact lungs.

Methods:  Sixteen pigs were randomly selected to receive either a continuous thiopentone infusion (control group, n = 8) or sevoflurane (n = 8) at 4.0% inspiratory concentration (1.5 MAC) in air for 6 h. Bronchoalveolar lavage samples were collected at the end of the study to determine pulmonary inflammatory markers.

Results:  Compared with thiopentone anaesthesia, significant increases in BAL leukotriene C4 (LTC4), NO3‐, and NO2‐ levels were observed after sevoflurane anaesthesia. In addition, there was a significant decrease in total blood leukocyte count in sevoflurane‐treated animals.

Conclusion:  We conclude that sevoflurane increases pulmonary LTC4, NO3‐, and NO2‐ production in pigs, indicating an inflammatory response.
Direct myocardial depressant effect of naloxone: mechanical and electrophysiological actions in vitro
Authors: Kim Ki Jun , Chung Nam‐sik , Park Wyun Kon
Published: December 2003

Background:  Naloxone, an opioid antagonist, has a cardiovascular pressor effect and has been used in various types of shock states. The aim was to determine the non‐opioid effect on direct cardiac muscle contractility and explore the mechanism using guinea pig right ventricular papillary muscles.

Methods:  With institutional approval, isometric contractile force was measured in modified normal and 26 mM K+ Tyrode solution at various stimulation rates. The effects of naloxone on sarcoplasmic recticulum function were evaluated by measuring rested‐state contraction in low Na+ (25 mM) Tyrode solution and rapid cooling contracture in modified normal Tyrode solution. Normal and slow action potentials (APs) were measured using conventional microelectrode technique. Patch clamp study was performed to examine the direct effect on Ca2+ current in cardiac ventricular myocytes.

Results:  Naloxone (50, 100, and 200 µM) caused a concentration‐dependent depression of peak force and maximal rate of force development. Modest depression, approximately 20%, was shown in rested‐state contraction in low Na+ Tyrode solution. Naloxone (100 µM) modestly depressed the rapid cooling contracture to 80 ± 3% of baseline, accompanied by prolongation of time to peak contracture by approximately 37%. In 26 mM K+ Tyrode solution, naloxone (100 µM) markedly and selectively depressed the late force development. While naloxone (100 µM) did not alter the amplitude and dV/dt‐max in normal and slow APs at 0.25 Hz, AP duration was prolonged significantly. In patch clamp experiment, naloxone (50 µM) depressed Ca2+ current by approximately 50%.

Conclusions:  The direct myocardial depressant effect of naloxone appeared to be in part caused by depression of Ca2+ influx through cardiac membrane. Sarcoplasmic reticulum function appeared to be modestly depressed.
Fluid challenge in patients at risk for fluid loading‐induced pulmonary edema
Authors: Matejovic M. , Krouzecky A. , Rokyta R. , Novak I.
Published: December 2003

Background:  This study evaluated the effects of protocol‐guided fluid loading on extravascular lung water (EVLW) and hemodynamics in a group of patients at high risk for volume expansion‐induced pulmonary and systemic edema.

Methods:  Nine acutely admitted septic patients with acute lung injury (ALI) were prospectively studied. In addition to sepsis and ALI, the following criteria indicating increased risk for edema formation had to be fulfilled: increased vascular permeability defined as microalbuminuria greater than fivefold normal and hypoalbuminemia <30 g l−1. Two hundred‐ml boluses of a 10% hydroxyethyl starch (HES) was titrated to obtain best filling pressure/stroke volume relation. Extravascular lung water and intrathoracic blood volume (ITBV) were measured using a transpulmonary double‐indicator dilution technique. Baseline data were compared with data at the end of fluid loading and 3 h postchallenge.

Results:  At study entry the mean EVLW was 13 ml kg−1, and the mean EVLW/ITBV ratio (indicator of pulmonary permeability) was 0.72 (normal range 0.20–0.30). To attain optimal preload/stroke volume relation 633 ± 240 ml of HES was needed. Fluid loading significantly increased preload (CVP, PAOP and ITBV), and stroke volume. Effective pulmonary capillary pressure (Pcap) rose only slightly. As a result, the Pcap–PAOP gradient decreased. Despite increased cardiac output, EVLW did not change by plasma expansion.

Conclusion:  In this selected group of at‐risk patients, the optimization of cardiac output guided by the concept of best individual filling pressure/stroke volume relationship did not worsen permeability pulmonary edema.
Chronic pain following Caesarean section
Authors: Nikolajsen L. , Sørensen H.C. , Jensen T.S. , Kehlet H.
Published: December 2003

Background:  Chronic postoperative pain is a well‐recognized problem after various types of surgery such as amputation, thoracotomy, mastectomy, gallbladder surgery and inguinal hernia repair. However, little is known about chronic pain after gynaecologic surgery. Therefore, the aim was to study the incidence of chronic pain after Caesarean section.

Methods:  A questionnaire was sent in February/March 2003 to 244 consecutive patients who underwent Caesarean section in a one‐year period from 1 October 2001 to 30 September 2002. Patients were asked about duration of postoperative abdominal scar pain, and if pain was still present to describe the frequency and intensity of pain and its impact on daily life. The questionnaire also included questions about the Caesarean section and about pain problems elsewhere.

Results:  A total of 220 patients (90.2%) answered the questionnaire. The mean follow‐up time was 10.2 months (range 6–17.6). Postoperative pain resolved in most patients within 3 months but 27 patients (12.3%) still had pain at the time of the interview. No patients had constant pain, but in 13 of 27 patients (5.9%) pain was present daily or almost daily. Patients with persistent pain (n = 27) had more often undergone general than spinal anaesthesia for the Caesarean section. Frequencies of pain problems elsewhere and recalls of severe acute postoperative pain were also higher among patients with persistent pain.

Conclusion:  Chronic pain after Caesarean section seems to be a significant problem in at least 5.9% of patients.
The effect of carbon dioxide, respiratory rate and tidal volume on human heart rate variability
Authors: Pöyhönen M. , Syväoja S. , Hartikainen J. , Ruokonen E. , Takala J.
Published: December 2003

Background: Heart rate variability (HRV) has been used for assessment of depth of anesthesia. Alterations in respiratory rate and tidal volume modulate the sympatovagal neural drive to the heart. The changes in PaCO2that accompany changes in breathing pattern may, through chemoreceptors in the brainstem, independently influence the autonomic control of the heart and modulate HRV.

Methods: We measured the effects of PaCO2, tidal volume and respiratory rate on HRV during spontaneous and mechanical ventilation in 22 healthy volunteers and in 25 mechanically ventilated anesthetized patients.

Results: Adding CO2to the inspiratory gas increased high frequency (HF) and low frequency (LF) components of HRV in awake volunteers both during spontaneous and mechanical ventilation, while this effect of CO2was abolished in patients during anesthesia. Increase of tidal volume increased HF component of HRV only in volunteers during spontaneous ventilation. On the other hand, when respiratory rate was reduced, the balance of HF and LF power moved toward LF power in all study groups. Breathing frequency altered HRV independent on PaCO2, tidal volume and the level of consciousness. In contrast, the effect of PaCO2appeared to be related to normal level of consciousness, suggesting that a cortical modulation of the autonomic nervous activity contributes to the effects of PaCO2on HRV.

Conclusions: PaCO2, tidal volume and respiratory rate should be controlled when HRV power spectrum is measured in conscious patients or volunteers, while in anesthetized patients small changes in end‐tidal CO2or tidal volume do not modulate HRV if respiratory rate remains unchanged.
Complement activation, endothelin‐1 and neuropeptide Y in relation to the cardiovascular response to endotoxin‐induced systemic inflammation in healthy volunteers
Authors: Soop A. , Albert J. , Weitzberg E. , Bengtsson A. , Lundberg J. O. N. , Sollevi A.
Published: December 2003

Background:  Endotoxin is a major stimulus for triggering the host response in septicaemia. The pathophysiology of sepsis involves activation of the vascular endothelium and leukocytes, resulting in the release of various mediators, e.g. cytokines, nitric oxide (NO), endothelin (ET‐1) and complement factors. We evaluated the blood levels of complement activation, ET‐1 and neuropeptide Y (NPY) in parallel with the haemodynamic and oxygen transport response during human experimental endotoxemia.

Methods:  Eleven healthy men had venous, arterial and pulmonary arterial catheters placed for continuous haemodynamic measuring. After 30 min rest endotoxin (E. Coli 4 ng kg−1, Lot G1) was intravenously administered. Blood samples from pulmonary and arterial catheters were collected hourly over 4 h.

Results:  Body temperature augmented significantly from baseline values (36.7 ± 0.7 °C, mean ± SEM) with a maximum after 3.5 h (39.1 ± 0.3 °C, P < 0.001). Cardiac output increased by 100%, systemic vascular resistance decreased by 50%, the oxygen consumption and the tissue oxygen transport increased. Activation of the complement system was indicated by an increase in SC5b‐9. Endothelin‐1‐like immunoreactivity (ET‐1‐LI) increased over time in arterial blood. NPY‐like immunoreactivity (NPY‐LI) did not change over time.

Conclusion:  A dose of endotoxin associated with reproducible systemic vasodilation and fever in healthy subjects causes complement activation and increased systemic levels of ET‐1‐LI, illustrating that the model is a useful tool for inducing moderate systemic inflammation where several mediator systems are activated.
Ventriculo‐arterial coupling and mechanical efficiency with remifentanil in patients with coronary artery disease
Authors: Pittarello D. , Bonato R. , Marcassa A. , Pasini L. , Falasco G. , Giron G. P.
Published: December 2003

Background:  Optimum transfer of energy from the left ventricle to the arterial circulation requires appropriate matching of these mechanical systems. Left ventricular‐arterial coupling describes this relationship between the ventricular elastance (Ees) and arterial elastance (Ea). The ratio of these elastances defines the efficiency of myocardium and provides in our study a useful technique for assessment of the actions of remifentanil. The purpose of this study was to evaluate the effects of remifentanil on ventriculo‐arterial coupling in cardiac surgery in patients with coronary artery disease.

Methods:  Fourteen patients with coronary artery disease, submitted intraoperatively to cardiac anesthesia for myocardial revascularization, were examined prospectively. With the use of transesophageal echocardiography (TEE) and different dicrotic arterial pressures, we determined the ventricle elastance (Ees), the arterial elastance (Ea) and myocardial efficiency before and after administration of a slow‐bolus of remifentanil (1 µ kg−1).

Results:  Remifentanil decreases significantly the ventricular elastance (from 6.09 mmHg ml−1 m−2 to 4.88) (P < 0.05), with a less, but however, significant decrease of arterial elastance (from 3.68 mmHg ml−1 m−2 to 3.13) (P < 0.05). Despite causing simultaneous declines, maintains a good myocardial efficiency (0.64–0.68) with no significant difference.

Conclusion:  Although remifentanil depresses ventricular and arterial elastance, preserves a good left ventricular‐arterial coupling and mechanical efficiency, despite a little increase of coupling. However, these effects are maintained only during a slow intravenous infusion and are dose‐dependent with impairment of coupling, that may contribute to decline in overall cardiovascular performance, at higher anesthetic dose and rapid infusion in patients with a severe myocardial dysfunction.
Brain injury after adult cardiac surgery
Authors: Ahonen J. , Salmenperä M.
Published: December 2003

Despite remarkable progress in surgical, cardiopulmonary bypass and anaesthetic techniques during the last three decades, brain damage remains an important complication of adult cardiac surgery. Effective brain protection strategies are already implemented today, but ongoing research is needed to meet the challenges faced in operating on increasingly old and disabled patients. The incidence of brain injury may be reduced by modifying the surgical procedure according to carotid duplex scanning and epiaortic echocardiography, by using techniques to reduce microembolization during cardiopulmonary bypass and by optimizing patient temperature during and after surgery. Increased knowledge will aid in choosing the best procedure or combination of procedures in each case to ensure that risks do not outweigh benefits.
Bilateral occipital neuropathy as a rare complication of positioning for thyroid surgery in a morbidly obese patient
Authors: Schulz‐Stübner S.
Published: December 2003

Background:  Peripheral neuropathies in various locations are described as complications after anesthesia and surgery. This is the first case report of temporary bilateral occipital neuropathy from positioning for thyroid surgery in a morbidly obese patient.

Methods:  A 48‐year‐old women with a history of depression, fibro‐myalgia, asthma, sleep apnea, diabetes mellitus and morbid obesity (127 kg, 165 cm) underwent 4 hours anesthesia with propofol/remifentanil without muscle relaxation for thyroid surgery. The neck with a very low range of motion secondary to fat tissue needed to be extended to facilitate surgery as much as possible. The head was carefully padded and there were no episodes of hypotension or hypoxemia throughout the case or in the PACU. At post op day 1 she complained of bilateral numbness in the distribution area of both greater occipital nerves. On post op day 2 tingling sensations and improvement of numbness was noticed. The patient recovered without residual symptoms after 6 weeks.

Conclusion:  Pressure or shear stress to the nerve, hypoperfusion or metabolic disturbances are discussed as the leading etiology of nerve damage during surgery in the literature. Pressure from fat tissue during prolonged head extension for surgery seems to be the cause in this case and should therefore be avoided whenever possible in morbidly obese patients, especially when other risk factors for neuropathy like diabetes are present.
Direct vascular effects of HR780, a novel 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor
Authors: Wajima Teruaki , Makita Shigeki , Oshima Kenichi
Published: December 2003

1. We have examined the effects of HR780, a novel 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitor, on porcine endothelial cell (EC) injury induced by xanthine (X)/xanthine oxidase (XO), a source of superoxide anion. Furthermore, the effects of HR780 on platelet‐derived growth factor (PDGF)‐induced migration and fetal calf serum (FCS)‐induced proliferation of rabbit smooth muscle cells (SMC) were investigated.

2. Probucol, at 10 µmol/L, significantly (P < 0.001) and completely suppressed lactate dehydrogenase leakage induced by X/XO. At 10 µmol/L, HR780 significantly (P = 0.010) inhibited X/XO‐induced EC injury.

3. HR780 dose‐dependently inhibited PDGF‐induced SMC migration and FCS‐induced SMC proliferation. The addition of mevalonate completely abolished the inhibitory effect of HR780 on SMC proliferation. Another HMG‐CoA reductase inhibitor, simvastatin (0.1–100 µmol/L), also inhibited the migration and proliferation responses as potently as HR780. In contrast, pravastatin (0.1–100 µmol/L) did not show any effects.

4. This in vitro study provides the first evidence that HR780 protects the vascular endothelium from oxidant stress and inhibits the migration and proliferation of SMC.
Analgesic duration and kinetics of liposomal bupivacaine after subcutaneous injection in mice
Authors: Grant GJ , Piskoun B , Bansinath M
Published: December 2003

1. The objective of the present study was to assess the time‐course profile of analgesia and bupivacaine concentrations at the site of injection after subcutaneous administration of a single dose of standard bupivacaine or a novel controlled‐release liposomal bupivacaine formulation.

2. Groups of mice were injected subcutaneously with 0.2 mL of 0.5% standard bupivacaine or 0.5, 1 or 2% liposomal bupivacaine.

3. A prolonged duration of analgesia occurred in mice receiving liposomal bupivacaine. In the liposomal groups, the bupivacaine remained at the injection site for more than 96 h, compared with approximately 8 h in groups injected with standard bupivacaine.

4. These results confirm that the prolonged analgesia observed after injection of the liposomal formulation is associated with sustained higher levels of bupivacaine at the site of injection.
Vascular non‐endothelial nitric oxide induced by swimming exercise stress in rats
Authors: Chies AB , Corrêa FMA , De Andrade CR , Rosa‐e‐Silva AAM , Pereira FC , De Oliveira AM
Published: December 2003

1. Herein, we report the effects of acute or chronic forced swimming on vascular responsiveness to angiotensin (Ang) II.

2. The possible involvement of locally produced substances, such as nitric oxide (NO) and prostanoids, in these effects were studied in rat thoracic aorta and superior mesenteric arteries.

3. Chronic, but not acute, swimming reduced the efficacy (maximal effect; Emax) of AngII in thoracic aorta and mesenteric arteries, either with intact or denuded endothelium.

4. The efficacy of AngII was reduced in the presence of indomethacin in mesenteric arteries, but not in the aorta, from either control or chronically stressed rats.

5. Treatment with NG‐monomethyl‐l‐arginine reversed the effect of chronic stress on the response to AngII, suggesting that chronic stress may increase non‐endothelial NO activity in both the aorta and mesenteric arteries.

6. The effects of acute and chronic stress on vascular reactivity were selective for AngII because no changes were observed on the effects of phenylephrine.
Cosegregation analysis of natriuretic peptide genes and blood pressure in the spontaneously hypertensive rat
Authors: Ye Ping , West Malcolm J
Published: December 2003

1. The natriuretic peptide precursor A (Nppa) and B (Nppb) genes are candidate genes for hypertension and cardiac hypertrophy in the spontaneously hypertensive rat (SHR). The purpose of the present study was to determine the role of the Nppa and Nppb genes in the development of hypertension in the SHR.

2. A cohort (n = 162) of F2 segregating intercross animals was established between strains of hypertensive SHR and normotensive Wistar‐Kyoto rats. Blood pressure and heart weight were measured in each rat at 12–16 weeks of age. Rats were genotyped using 11 informative microsatellite markers, distributed in the vicinity of the Nppa marker on rat chromosome 5 including an Nppb marker. The phenotype values were compared with genotype using the computer package mapmaker 3.0 (Whitehead Institute, Boston, MA, USA) to determine whether there was a link between the genetic variants of the natriuretic peptide family and blood pressure or cardiac hypertrophy.

3. A strong correlation was observed between the Nppa marker and blood pressure. A quantitative trait locus (QTL) for blood pressure on chromosome 5 was identified between the Nppa locus and the D5Mgh15 marker, less than 2 cM from the Nppa locus. The linkage score for the blood pressure QTL on chromosome 5 was 3.8 and the QTL accounted for 43% of the total variance of systolic blood pressure, 54% of diastolic blood pressure and 59% of mean blood pressure. No association was found between the Nppb gene and blood pressure. This is the first report of linkage between the Nppa marker and blood pressure in the rat. There was no correlation between the Nppa or Nppb genes or other markers in this region and either heart weight or left ventricular weight in F2 rats.

4. These findings suggest the existence of a blood pressure‐dependent Nppa marker variant or a gene close to Nppa predisposing to spontaneous hypertension in the rat. It provides a strong foundation for further detailed genetic studies in congenic strains, which may help to narrow down the location of this gene and lead to positional cloning.
Morphological evidence of reinnervation of the baroreceptive regions in sinoaortic‐denervated rats
Authors: Cai Guo‐Jun , Li Ling , Xie He‐Hui , Xu Jia‐Jun , Miao Chao‐Yu , Su Ding‐Feng
Published: December 2003

1. The arterial baroreflex (ABR) plays an important role in the maintenance of the stability of blood pressure. Sinoaortic denervation (SAD) destroys the integrity of the reflex arc and produces severe organ damage in rats. However, partial recovery of ABR function has been observed following chronic denervation. The aim of the present study was to determine whether there was morphological evidence of reinnervation of the aortic arch and carotid sinus following SAD.

2. A substantial body of physiological and morphological evidence suggests that substance P (SP) may be a neurotransmitter contained in first‐order sensory baroreceptor afferents; therefore, the patterns of vascular SP and neurofilament (NF) immunoreactive (IR) innervation of the aortic arch and carotid sinus were investigated in the present study.

3. Ten‐week‐old male Sprague‐Dawley rats underwent SAD or sham operation. Whole mounts of carotid bifurcation and aortic arch were prepared for immunohistochemical study at various time points (1, 9 and 16 weeks after operation).

4. The results of computerized image analysis show that the mean density of NF‐ and SP‐IR nerves of SAD rats 9 and 16 weeks after operation increased gradually and significantly compared with that of rats 1 week after operation.

5. In conclusion, the results indicate that there is reinnervation of the aortic arch and carotid sinus by NF‐ and SP‐IR fibres in SAD rats, which may be the morphological basis for the partial restoration of ABR function over time after SAD.
Phytosterol additives increase blood pressure and promote stroke onset in salt‐loaded stroke‐prone spontaneously hypertensive rats
Authors: Ogawa Hiroshi , Yamamoto Kazuo , Kamisako Toshinori , Meguro Tadamichi
Published: December 2003

1. To assess the effect of dietary phytosterol on stroke and the lifespan of salt‐loaded stroke‐prone spontaneously hypertensive rats (SHRSP), we investigated the effects of the addition of phytosterol to soybean oil (phytosterol content: 0.3%) on stroke onset, lifespan following onset of stroke and overall lifespan compared with canola oil (phytosterol content: 0.9%).

2. Six‐week‐old male SHRSP were fed a test diet prepared by the addition of canola oil (CA diet), soybean oil (SO diet), soybean oil plus 0.6% phytosterol (SO + 0.06P diet) or soybean oil plus 4.5% phytosterol (SO + 0.45P diet) as a 10% fat source.

3. Systolic blood pressure (SBP) increased in the SO + 0.06P and SO + 0.45P groups compared with the SO group and the increase was dependent on the amount of phytosterol added, indicating that the addition of phytosterol to soybean oil may promote an increase in SBP in salt‐loaded SHRSP.

4. The onset of stroke was shortest in the SO + 0.45P group and survival after the onset of stroke was shortest in the CA group. Consequently, the SO + 0.45P and CA groups showed marked lifespan shortening, indicating that a fivefold greater amount of phytosterol was required to produce an effect equivalent to that of canola oil.

5. Investigation of the mRNA expression of ATP‐binding cassette (ABC) transporters involved in intestinal phytosterol absorption indicated significant decreases in the intestinal mRNA expression of Abcg5 and Abcg8 in SHRSP and Wistar‐Kyoto rats compared with Wistar rats.

6. In conclusion, the addition of phytosterol to soybean oil elevated SBP and promoted the onset of stroke, which may cause a reduction in survival time. However, a fivefold greater amount of phytosterol was required to produce an effect that was equivalent to the survival time‐shortening effect of canola oil. The significant decrease in the intestinal mRNA expression of Abcg5 and Abcg8 in SHRSP may be responsible, at least in part, for the unfavourable effects observed following the addition of phytosterol.
Effect of salt and water intake on epithelial sodium channel mRNA abundance in the kidney of salt‐sensitive Sabra rats
Authors: Nicco Carole , Bankir Lise , Bouby Nadine
Published: December 2003

1. The level of mRNA expression of epithelial sodium channel (ENaC) subunits was studied in a salt‐dependent hypertensive rat strain (Sabra). These rats exhibit high vasopressin levels compared with their normotensive counterparts. We also investigated whether this expression is influenced by changes in the sodium intake/aldosterone axis or in the fluid intake/vasopressin axis.

2. A higher expression of β‐ and γ‐subunit mRNA was found in salt‐sensitive compared with salt‐resistant rats on a normal salt diet. A high‐sodium diet did not alter mRNA abundance in either substrain. In contrast, water supplementation in salt‐sensitive rats fed the high‐sodium diet induced a marked reduction in mRNA abundance of β‐ and γ‐subunits.

3. The present study provides evidence that β‐ and γ‐subunits of ENaC are differently expressed in the kidney of salt‐sensitive and salt‐resistant Sabra rats and that their abundance is regulated by vasopressin, not by sodium intake. These results are consistent with the hypothesis that increased vasopressin‐dependent ENaC expression and activity may contribute to the pathogenesis of hypertension in salt‐sensitive Sabra rats.
Role of angiotensin AT1 and AT2 receptors in cardiac hypertrophy and cardiac remodelling
Authors: Zhu Yi‐Chun , Zhu Yi‐Zhun , Lu Ning , Wang Ming‐Jie , Wang Yan‐Xia , Yao Tai
Published: December 2003

1. Left ventricular hypertrophy (LVH) is an independent cardiovascular risk factor. Angiotensin AT1 receptor antagonism has been considered as a specific approach to block the renin–angiotensin system and been demonstrated to be able to prevent or regress LVH by interfering with the remodelling process of the heart.

2. Angiotensin AT1 receptor blockade induces a marked increase in angiotensin (Ang) II, which may stimulate the AT2 receptors. Gene expression of AT1 and AT2 receptors increases in a time‐dependent manner in cardiac remodelling following myocardial infarction.

3. Considerable efforts have been made to clarify the role of AT2 receptors in cardiac hypertrophy and remodelling since the mid‐1990s, resulting in controversial reports: the AT2 receptor mediates actions either opposite to or in coordination with those of the AT1 receptor. Moreover, there are many reports of no significant effects mediated by AT2 receptors.

4. Based on the studies reviewed in the present article, we assume that the predominant effect of AngII in cardiac hypertrophy and cardiac remodelling is growth promoting and that this effect is mediated mainly via AT1 receptors. The AT2 receptors may affect the hypertrophic process by interacting with other cardiac membrane proteins, enzymes and autacoids. Before coming to a conclusion as to whether AT2 receptor stimulation or antagonism is beneficial to the heart, more studies should be performed in different LVH models, especially long‐term treatment protocols in vivo.
Therapeutic options for esophageal cancer
Authors: LAW SIMON , WONG JOHN
Published: December 2003

Options for the treatment of esophageal cancer used to be very limited, with surgical resection and radiotherapy methods aimed at both cure or palliation, and, in those unfortunate patients with severe dysphagia, intubation with a plastic prosthesis to restore esophageal luminal patency. Progress in the management of this cancer in the past two decades includes refinement in surgical techniques and perioperative care, better radiological staging methods, enhanced means of planning and delivering radiotherapy, multimodality treatments, and better designs in esophageal prosthesis. For individual patients, a stage‐directed therapeutic plan can be used. Long‐term survival, however, remains suboptimal for this deadly disease. The current review presents an overview of the commonly employed therapeutic options for esophageal cancer at the beginning of the 21st century.
Expression of Mg2+‐dependent, HCO3–‐stimulated adenine triphosphatase in the human duodenum
Authors: KONNO YUTAKA , KATO KATSUAKI , DAIRAKU NAOHIRO , KOIKE TOMOYUKI , IIJIMA KATSUNORI , IMATANI AKIRA , SEKINE HITOSHI , OHARA SHUICHI , SHIMOSEGAWA TOORU
Published: December 2003

Background and Aim:  Mg2+‐dependent, HCO3–‐stimulated adenine triphosphatase (Mg2+‐HCO3–‐ATPase) is an enzyme that catabolizes ATP in the presence of HCO3– and Mg2+. The activity of this ATPase is known to be present in the duodenum, but its physiological role remains unclear. In the present study, the aim was to study the distribution and biochemical profiles of Mg2+‐HCO3–‐ATPase in the human duodenum.

Methods:  The histochemistry of Mg2+‐HCO3–‐ATPase, its localization using electron microscopy (EMS), and the measurement of enzyme activity were carried out by using mucosal samples of the bulb, and the second and third portions of the duodenum, obtained from six volunteers by endoscopic biopsy.

Results:  The Mg2+‐HCO3–‐ATPase was detected in the brush border along the luminal surface of human duodenal epithelial cells. The EMS confirmed its localization to the surface of microvilli. The activity of Mg2+‐HCO3–‐ATPase was higher in the distal portions of the human duodenum than in the bulb. Its maximal activity was obtained under a pH of 8.5, and in the presence of 1.0 mmol/L MgCl2 and 50 mmol/L NaHCO3, but the activity was undetectable in pH <7.4 or >9.5.

Conclusion:  The results of the present study suggested that Mg2+‐HCO3–‐ATPase may work for luminal alkalization in the distal portions of the human duodenum and may contribute to maintaining the activity of pancreatic digestive enzymes.
Cost‐effectiveness of colorectal cancer screening: Comparison of community‐based flexible sigmoidoscopy with fecal occult blood testing and colonoscopy
Authors: O'LEARY BETH A , OLYNYK JOHN K , NEVILLE A MUNRO , PLATELL CAMERON F
Published: December 2003

Background and Aims:  To determine the cost‐effectiveness of screening for colorectal cancer using flexible sigmoidoscopy once every 10 years, compared with annual and biennial rehydrated Hemoccult fecal occult blood testing and colonoscopy once every 10 years, or no screening.

Methods:  A Markov model was developed in order to simulate the progression of a cohort of asymptomatic, average‐risk individuals aged 55–64 years who were moving through a defined series of states towards death. The main outcome measures were: cases of colorectal cancer averted, colorectal cancer deaths averted, and cost per life‐year saved.

Results:  Colonoscopy averted the greatest number of cases of colorectal cancer (35%), followed by flexible sigmoidoscopy (25%), and annual (24%) and biennial (14%) fecal occult blood testing. Colonoscopy averted the greatest number of deaths from colorectal cancer (31%), followed by annual fecal occult blood testing (29%), flexible sigmoidoscopy (21%) and biennial fecal occult blood testing (19%). Flexible sigmoidoscopy was the most efficient in terms of cost per life‐year saved (A$16 801), followed by colonoscopy (A$19 285), biennial (A$41 183), and annual (A$46 900) fecal occult blood testing.

Conclusions:  Flexible sigmoidoscopy and colonoscopy are cost‐effective strategies for reducing the disease burden of colorectal cancer.
Digital quantification of fibrosis in liver biopsy sections: Description of a new method by Photoshop software
Authors: DAHAB GAMAL M , KHERIZA MOHAMED M , EL‐BELTAGI HUSSIEN M , FOUDA ABDEL‐MOTAAL M , EL‐DIN OSAMA A SHARAF
Published: December 2003

Background:  The precise quantification of fibrous tissue in liver biopsy sections is extremely important in the classification, diagnosis and grading of chronic liver disease, as well as in evaluating the response to antifibrotic therapy. Because the recently described methods of digital image analysis of fibrosis in liver biopsy sections have major flaws, including the use of out‐dated techniques in image processing, inadequate precision and inability to detect and quantify perisinusoidal fibrosis, we developed a new technique in computerized image analysis of liver biopsy sections based on Adobe Photoshop software.

Methods:  We prepared an experimental model of liver fibrosis involving treatment of rats with oral CCl4 for 6 weeks. After staining liver sections with Masson's trichrome, a series of computer operations were performed including (i) reconstitution of seamless widefield images from a number of acquired fields of liver sections; (ii) image size and solution adjustment; (iii) color correction; (iv) digital selection of a specified color range representing all fibrous tissue in the image and; (v) extraction and calculation.

Results:  This technique is fully computerized with no manual interference at any step, and thus could be very reliable for objectively quantifying any pattern of fibrosis in liver biopsy sections and in assessing the response to antifibrotic therapy. It could also be a valuable tool in the precise assessment of antifibrotic therapy to other tissue regardless of the pattern of tissue or fibrosis.
Five‐lipoxygenase‐activating protein inhibitor MK‐886 induces apoptosis in gastric cancer through upregulation of p27kip1 and bax
Authors: FAN XIAO MING , TU SHUI PING , LAM SHIU KUM , WANG WEI PING , WU JING , WONG WAI MAN , YUEN MAN FUNG , LIN MARIE CHIA MI , KUNG HSIANG FU , WONG BENJAMIN CHUN‐YU
Published: December 2003

Background and Aim:  Products of the arachidonic acid metabolizing enzyme, 5‐lipoxygenase (5‐LOX), stimulate the growth of several cancer types. Inhibitors of 5‐LOX and 5‐LOX‐activating protein (FLAP) induce apoptosis in some cancer cells. Here, the authors investigated the effect of a FLAP inhibitor, MK‐886, on the inhibition of proliferation and induction of apoptosis in gastric cancer.

Methods:  Cell proliferation in gastric cancer cells was measured using an 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide assay. Apoptosis was measured using acridine orange staining and flow cytometry. Protein expression of apoptosis‐related genes p53, p21waf1, p27kip1, bcl‐2 families, cytochrome c, and the caspases were examined using Western blotting. Caspase‐3 activity was measured using colorimetric assay of substrate cleavage.

Results:  MK‐886 inhibited cell growth in a dose‐ and time‐dependent manner. Apoptosis was induced in gastric cancer cells and was characterized by upregulation of p27kip1 and bax, with release of cytochrome c from mitochondria into cytosol, which initiated caspase‐3 activation. Specific caspase‐3 inhibitors partially blocked MK‐886‐induced apoptosis.

Conclusion:  The present results suggest that MK‐886 induces apoptosis in gastric cancer cells through upregulation of p27kip1 and bax, and that MK‐886 is a potentially useful drug in gastric cancer prevention and therapy.
Wireless capsule endoscopy: Experience in a tropical country
Authors: SRIRAM PVJ , RAO GV , REDDY D NAGESHWAR
Published: December 2003

Background and Aim:  Capsule endoscopy is fast becoming the procedure of choice for small bowel imaging, especially to investigate the cause of unexplained gastrointestinal (GI) bleeding. We report our experience with capsule endoscopy in 24 cases with various indications.

Methods:  In patients with unexplained GI bleeding or chronic anemia, the cause could be established in nine of 12 cases (75%), which included angioectasiae, leiomyomata and parasitic infestation.

Results:  The yield of capsule endoscopy was highest in patients presenting with chronic diarrhea and suspicion of small bowel mucosal disease, where Crohn's disease and tuberculosis could be diagnosed. However, in patients with unexplained abdominal pain, capsule endoscopy was found to be least useful because 5/7 patients in the study were normal, emphasizing the importance of case selection. Overall, capsule endoscopy yielded a positive diagnosis in 16 of the 24 cases (66.6%).

Conclusions:  The experience of capsule endoscopy in a tropical clinical setting is no different from elsewhere, although certain conditions like worm infestation are more likely to be detected in this environment.