bluuebunny/crossref_metadata_2025 huggingface dataset:
HUMAN CYTOCHROME P450 ENZYMES EXPRESSED IN BACTERIA: REAGENTS TO PROBE MOLECULAR INTERACTIONS IN TOXICOLOGY
Authors: Gillam Elizabeth MJ
Published: June 2007

1. Phase I metabolism of drugs is accomplished by the concerted actions of a limited number of cytochrome P450 enzymes with wide but often overlapping substrate specificities. Although metabolism generally accelerates the clearance of drugs, reactive products may also be generated that cause toxic effects.

2. Because individuals vary in the range and levels of different P450 forms, it is useful to be able to determine the specific isoforms involved in a particular metabolic reaction, in order to estimate the extent of variation within a population in the pharmacokinetics of specific drugs. Such studies may also allow predictions to be made regarding the relative susceptibility of different individuals to possible adverse effects associated with drug treatment.

3. Human cytochrome P450 enzymes are now routinely expressed as recombinant proteins in many different systems, including mammalian cell culture, yeast, baculovirus and Escherichia coli. The latter system is particularly useful when large amounts of protein are required for biophysical studies, but can also be adapted to routine examination of pathways of drug metabolism and toxicology.

4. The present review provides an analysis of strategies used for enhancing cytochrome P450 expression in bacteria and for examining the activity of the recombinant proteins. The potential applications of recombinant P450 are discussed, with particular emphasis on investigation of the roles of cytochrome P450 forms in the metabolism and the toxicity of drugs.
A NEW METHOD FOR COMBINED ISOMETRIC AND ISOBARIC PHARMACODYNAMIC STUDIES ON PORCINE CORONARY ARTERIES
Authors: Tankó László B , Mikkelsen Erich O , Frøbert Ole , Bagger Jens P , Gregersen Hans
Published: June 2007

1. The principal aim of the present study was to explore the isometric and isobaric capacity of a new intravascular technique, impedance planimetry, in basic pharmacodynamic investigations on porcine isolated epicardial coronary arteries.

2. The balloon‐based catheter technique provides simultaneous measurements of luminal cross‐sectional area and pressure. Sources of errors that may influence the accuracy of measurements were evaluated in detail.

3. Under isometric conditions, the stretch ratio‐tension diagram showed typical developments of resting and active tensions of the smooth muscle when exposed to alternating maximal K+ depolarization and mechanical stretching. The mean (±SEM) maximum active tension was 28.43 ± 1.72 mN/mm, which was reached at a stretch ratio of 1.26 ±0.02, corresponding to a resting tension of 10.50±0.53 mN/mm (n= 7). The concentration‐response relationship to K+ at optimal basal tension was characterized by a mean (±SEM) pD2 value of 1.67±0.01 (n= 7).

4. Under isobaric conditions in the pressure range 40‐140 mmHg, the method allowed the investigation of active vascular responses to partial K depolarization. The maximal active response to 25 mmol/L K+ was found at the transmural pressure of 60 mmHg (n= 7). To obtain full K+ concentration‐response curves, a basal tension corresponding to a transmural pressure of 120 mmHg was required. The mean (±SEM) pD2 value for the concentration‐response relationship to K+ was 1.53±0.01 (n= 10).
DECREASE WITH AGE IN FREQUENCY OF THE HOMOZYGOUS DELETIONAL ANGIOTENSIN‐CONVERTING ENZYME GENOTYPE IN HYPERTENSIVE PATIENTS*
Authors: Cheung Bernard MY , Lau Chu‐Pak , Leung Raymond YH , Tan Kathryn CB
Published: June 2007

1. Angiotensin‐converting enzyme (ACE) genotypes in hypertensive patients were studied in order to delineate their cardiovascular risk due to the ACE gene. We hypothesized that the distribution of ACE genotypes may change with age because of the risk of myocardial infarction associated with the homozygous deletional (DD) genotype.

2. A total of 223 subjects were recruited from the Hypertension Outpatient Clinic of the Sai Ying Pun Hospital with consent. They consisted of 75 patients with newly diagnosed or documented hypertension, 46 patients with ischaemic heart disease and 102 normal controls. Genomic DNA was extracted from peripheral leucocytes and amplified by polymerase chain reaction. Insertion (I) or deletion (D) alleles were identified after electrophoresis. The frequencies of ACE genotypes and alleles were measured in three age groups: < 50 years, 50‐59 years and > 60 years.

3. A significant correlation between ACE genotype and age was found (P= 0.03). The relative frequency of the D allele in those under 50 years of age was similar in controls and hypertensive patients (0.40 vs 0.41; P = 0.94), but was significantly lower in patients ≥ 50 years compared with those patients < 50 years of age (0.22 vs 0.41; P = 0.01).

4. The observed decrease in frequency of the DD genotype in older hypertensive patients is consistent with the increase in cardiovascular risk associated with the D allele and raises the possibility that the DD genotype may increase the risk of premature death, at least in the population studied.
EFFECTS OF CHROMAN DERIVATIVES ON PLATELET AGGREGATION INDUCED BY SOME AGGREGATING AGENTS IN RABBITS
Authors: Aida Yoko , Kasama Toshio , Fukaya Hiroaki , Takeuchi Naoki , Sugiyama Kumiko , Tobinaga Seisho
Published: June 2007

1. We synthesized 10 chroman derivatives (CD‐1 to CD‐10) derived from khellactone, including praeruptorin A and praeruptorin B and examined the effects of these compounds on rabbit platelet aggregation.

2. These compounds exhibited an inhibitory effect on platelet‐activating factor (PAF)‐induced platelet aggregation and their effects were more potent on PAF‐induced platelet aggregation than on adenosine triphosphate (ADP)‐, arachidonate (AA)‐ or collagen‐induced platelet aggregation. In particular, (±)‐cis‐5‐methoxy‐6‐methoxycarbonyl‐2,2‐dimethyl‐3,4‐ditiglyloxychro‐man (CD‐6), (±)‐cis‐5‐methoxy‐6‐(2‐methoxycarbonylethenyi)‐2,2‐dimethyl‐3,4‐ditiglyloxychroman (CD‐8), (±)‐cis‐3,4‐diacetoxy‐5‐methoxy‐2,2‐dimethyl‐6‐propylchroman (CD‐9) and (±)‐cis‐5‐methoxy‐2,2‐dimethyl‐6‐propyl‐3,4‐ditiglyloxy‐chroman (CD‐10) showed a moderate inhibition of PAF‐induced platelet aggregation.

3. From these findings, it is suggested that compounds with potent PAF antagonist activities have the following features: (i) a tiglyloxy moiety is required at the 3 and 4 positions; and (ii) the methoxy moiety is also required at the 5 position of chroman skeleton in khellactone.
THE NITRIC OXIDE SYSTEM AND CORTISOL‐INDUCED HYPERTENSION IN HUMANS
Authors: Kelly John J , Tam Sim H , Williamson Paula M , Lawson Jane , Whitworth Judith A
Published: June 2007

1. The aim of the present study was to assess the role of the nitric oxide (NO) system in cortisol‐induced hypertension in humans.

2. Plasma and urinary nitrate/nitrite concentrations and plasma concentrations of arginine and symmetric (SDMA) and asymmetric (ADMA) dimethyl arginine were measured in six subjects on a restricted nitrate diet who were treated with 80 mg/day Cortisol and in subjects on an unrestricted nitrate diet who were treated with Cortisol (80 mg/day, n= 6, or 200 mg/day, n= 10) for 5 days.

3. Cortisol significantly increased systolic and mean arterial pressure. Significant reductions in plasma nitrate/nitrite concentrations were observed in subjects on a restricted nitrate diet on days 3, 4 and 5 of Cortisol treatment (to 11±1, 10±1, 11± pmol/L, respectively) compared with pretreatment (16±1 pmol/L; P<0.01).There were no significant changes in plasma arginine, ADMA or SDMA concentrations.

4. Cortisol treatment significantly increased blood pressure and reduced plasma nitrate/nitrite concentrations. Reductions in plasma nitrate concentrations are not explained by changes in substrate availability or in endogenous nitric oxide synthase inhibitors. These data support a role for the NO system in cortisol‐induced hypertension in humans.
CEREBROVASCULAR PRESSURE TRANSMISSION ANALYSIS AS A GUIDE TO THE PATHOPHYSIOLOGY OF RAISED INTRACRANIAL PRESSURE
Authors: Lewis SB
Published: June 2007

1. Raised intracranial pressure (ICP) is a major factor associated with morbidity and mortality in patients with severe head injury. Identifying the mechanisms responsible for raised ICP may be difficult and, as a result, treatment prescribed may be non‐specific and often ineffective.

2. Research aimed at obtaining more information from measurement of ICP was initially focused on measurements of compliance. This was achieved by introducing fluid volume into the craniospinal compartment and measuring the response. Although shown to be clinically useful, associated technical problems have precluded the routine use of these measurements.

3. Cerebrovascular pressure transmission (CVPT) analysis has been suggested as an alternative method of deriving more information from the ICP wave‐form. Pressure transmission across the cerebrovascular bed is assessed by a systems analysis approach whereby blood pressure and ICP wave‐form pairs are resolved by fast Fourier transform analysis into component harmonic frequencies, each with a specific amplitude and phase. These are expressed as a ratio or ‘transfer function’ for each harmonic peak.

4. Laboratory models have identified specific CVPT patterns associated with various causes of raised ICP. These studies have been extended to clinical practice and have been used to define patterns of CVPT in head‐injured patients, which may be used to identify mechanisms responsible for raised ICP, thus assisting in directing treatment strategy. Clinical usefulness of this technique in patient management is currently under investigation.
THE CONSEQUENCES OF DEAFNESS AND CHRONIC INTRACOCHLEAR ELECTRICAL STIMULATION ON THE CENTRAL AUDITORY PATHWAYS
Authors: Hardie Natalie Anne
Published: June 2007

1. Auditory deprivation can result in significant morphological and physiological changes within the central auditory nervous system. These changes are generally more pronounced when the onset of deafness occurs early in development, as is the case with congenitally deaf children.

2. A review of the auditory plasticity literature suggests that some of these deafness‐induced changes may be preventable or partially reversible by electrical stimulation of the auditory nerve.

3. With the increasing application of cochlear implants in congenitally deaf children, it is important to evaluate the consequences of introducing electrical stimulation to the developing auditory nervous system.
PROPOFOL BLOCK OF CARDIAC SODIUM CURRENTS IN RAT ISOLATED MYOCARDIAL CELLS IS INCREASED AT DEPOLARIZED RESTING POTENTIALS
Authors: Saint David A , Tang Yulu
Published: June 2007

1. The effect of propofol on cardiac whole‐cell sodium currents and single sodium channels in rat isolated ventricular myocytes was examined using patch‐clamp techniques.

2. Propofol caused a block of the whole‐cell sodium current, the potency of block depending on the holding potential. When cells were held at ‐90 mV, the EC50 was 2.8 μg/mL. When cells were held more hyperpolarized (at ‐140 mV), the EC50 increased to 44.0 μg/mL.

3. Although the degree of block produced by the same concentration of propofol was different at different holding potentials, the time course of onset and recovery from block was the same.

4. The current/voltage relationship for the sodium current showed a pronounced block of peak current by propofol (40–50 % block of the maximum current by 30 μg/mL propofol), with a minimal shift in the voltage dependence of activation and no shift in reversal potential.

5. The voltage dependence of the steady state inactivation curve was shifted to more hyperpolarized potentials by propofol (shift of 18 and 8 mV by 30 and 10 μg/mL propofol, respectively).

6. Single channel records showed that propofol caused a shortening of the mean channel open time (from a mean of 0.59 to 0.38 ms by 10 μg/mL propofol), but no change in the channel amplitude.

7. It is concluded that propofol produces a block of sodium currents in cardiac myocytes at concentrations that are comparable to those that may be attained during anaesthesia.
BLUNTED NATRIURETIC RESPONSE TO ENDOGENOUS ATRIAL NATRIURETIC PEPTIDE DURING RAPID CARDIAC PACING IN ANAESTHETIZED DOGS
Authors: Yoneda Hikaru , Yamada Hiroshi , Yano Koji , Nishiyama Shinsuke , Naito Kazuaki
Published: June 2007

1. We investigated whether diuresis and natriuresis induced by endogenous atrial natriuretic peptide (ANP) were blunted during rapid cardiac pacing.

2. Changes in plasma ANP, renal function and haemody‐namics during rapid cardiac pacing were studied in anaesthetized closed‐chest dogs. Dogs were paced via the right ventricle at a rate of 200 b.p.m. (moderate pacing) or 250 b.p.m. (severe pacing) for 180 min.

3. The maximal increases in plasma ANP and urinary excretion of cGMP during severe pacing were four‐ and three‐fold higher, respectively, than those during moderate pacing. Despite the higher concentration of plasma ANP, the maximal increases in urine volume, urinary excretion of sodium and fractional excretion of sodium during severe pacing were similar to those during moderate pacing. Mean arterial pressure and renal vascular resistance were decreased only by severe pacing. The increase in total peripheral resistance during severe pacing was significantly smaller than that during moderate pacing. However, the glomerular filtration rate was kept at basal levels by both moderate and severe pacing.

4. These results suggest that there are certain mechanisms that counteract renal tubular sodium reabsorption induced by endogenous ANP under conditions of severe pacing. The suppression occurs at tubular sites but not at glomerular sites. One of the possibilities for the suppression is the decrease in renal perfusion pressure accompanied by decreases in peritubular capillary hydrostatic pressure.
CALCIUM CHANNEL BLOCKING AND VASODILATING ACTIONS OF THE NOVEL DIHYDROPYRIDINE DERIVATIVE AE0047
Authors: Nishikawa Masakuni , Gohda Maki , Shinyama Hiroshi , Matzno Sumio , Yamanaga Katsumi , Kido Hideaki , Nakamura Norifumi
Published: June 2007

1. The pharmacological characteristics of AE0047, a newly synthesized dihydropyridine (DHP) derivative, were investigated in vitro.

2. In bovine aortic membrane, AE0047 and other DHP calcium channel blockers (nitrendipine, nicardipine) displayed concentration‐dependent antagonism to specific [3H]‐PN200‐110 binding sites with the following values for inhibition constants (K1) obtained: 20.8±8.9, 12.3±4.5 and 3.9±1.0nmol/L for AE0047, nitrendipine and nicardipine, respectively.

3. In guinea‐pig ventricular myocytes, AE0047 blocked the L‐type calcium current, with values for the dissociation constant (Kd) and Hill coefficient of 11.4±5.7nmol/L and 0.852±0.061, respectively, indicating in the terms of Hill's hypothesis that one drug molecule blocks one calcium channel molecule.

4. In rat aorta, AE0047 inhibited 45Ca uptake induced by high K+(100mmol/L)by55%.

5. AE0047 and nitrendipine concentration dependently relaxed rat aortic strips contracted with 30 mmol/L KC1. The response to nitrendipine reached a plateau within 60 min and disappeared after drug washing. Interestingly, AE0047 required 5 h or more to produce a plateau of response, with no effect of drug washing. This confirmed the slow onset and long duration of its vasodilating action.

6. With AE0047, tissue content in rat aorta increased more slowly than with nitrendipine and release of AE0047 from tissue was also slower.

7. The data suggest that AE0047 is incorporated slowly into smooth muscle membranes, approaches receptors slowly through the membrane bilayer and accumulates in the membrane because of its high lipophilicity, resulting in an antihypertensive action that is slow in onset and of long duration.
PERMEABILITY OF THE DEVELOPING AND MATURE BLOOD‐BRAIN BARRIERS TO THEOPHYLLINE IN RATS
Authors: Habgood MD , Knott GW , Dziegielewska KM , Saunders NR
Published: June 2007

1. In the present study, the uptake of theophylline and L‐glucose into the adult and neonatal rat brain has been investigated. Steady state cerebrospinal fluid (CSF) and brain concentrations of theophylline were reached within 1 h following a single intraperitoneal (i.p.) injection, whereas steady state CSF and brain concentrations of L‐glucose were not approached until after 5 h.

2. Steady state brain:plasma and CSF:plasma concentration ratios for theophylline and L‐glucose in neonatal rats were significantly higher than ratios in adult rats. Erythrocyte:plasma ratios for theophylline in neonatal rats were also significantly higher than ratios in adult rats. Steady state ratios for theophylline were significantly higher than those for L‐glucose in both neonatal and adult rats.

3. Respiratory acidosis (pH 6.9–7.0) did not affect steady state CSF:plasma or brain.‐plasma ratios for theophylline in neonatal or adult rats. In contrast, steady state CSF:plasma and brain:plasma ratios for L‐glucose were increased by respiratory acidosis.

4. The lower steady state CSF:plasma, brain:plasma and erythrocyte:plasma ratios for theophylline in adult rats are likely to be due to a higher concentration of plasma proteins in adult blood compared with neonates, with a greater retention of protein‐bound (non‐exchangeable) theophylline in adult blood, and are unlikely to be due to p‐glycoprotein‐mediated efflux of theophylline at the adult blood‐brain barrier.
HYPOTHESIS: ALDOSTERONE IS SYNTHESIZED BY AN ALTERNATIVE PATHWAY DURING SEVERE SODIUM DEPLETION. ‘A NEW WINE IN AN OLD BOTTLE’
Authors: Boon Wah Chin , McDougall John G , Coghlan John P
Published: June 2007

1. The last three steps of aldosterone biosynthesis, 11β‐hydroxylation, 18‐hydroxylation and 18‐oxidation, have been demonstrated to be catalysed by one enzyme, which is the cytochrome P450np (CYP11B) in cow, pig, sheep and bullfrog or cytochrome P450aldo (CYP11B2) in rat, human, mouse and hamster.

2. The related enzyme P45011β (CYP11B1) from rat, human, mouse and hamster adrenals displays 11β‐hydroxylation and 18‐hydroxylation activities, but not 18‐oxidation activity in vitro. No such enzyme has been reported in the cow, pig or sheep to date.

3. Data showing the dissociation of aldosterone secretion from plasma angiotensin II (Angll) levels indicate the presence of other factor(s) that regulate aldosterone biosynthesis in response to changes in body sodium status. Thus, we propose the existence of a ‘sodium status factor’ that regulates aldosterone biosynthesis in addition to Angll, K,+ adrenocorticotropic hormone and atrial natriuretic peptide.

4. We propose that during severe sodium deficiency there is a switch in the aldosterone pathway to a pathway using 18‐hydroxy‐deoxycorticosterone (18‐OH‐DOC) rather than corti‐costerone as an intermediate. This switch may be mediated via the putative ‘sodium status factor’.

5. Two models of the hypothesis will be discussed in this paper: (i) a ‘one‐enzyme’ model; and (ii) a ‘two‐enzyme’ model.

6. The one‐enzyme model proposes that P450aldo (P45011β as in the case of the cow, sheep and pig) changes its enzymatic activity during severe sodium deficiency (i.e. switching to the alternative aldosterone biosynthesis pathway).

7. The two‐enzyme model proposes that, under normal circumstances, P450aldo synthesizes aldosterone from deoxycorticosterone, while during severe sodium deficiency the P450up provides the substrate (i.e 18‐OH‐DOC) for the P450aldo.
Community‐acquired methicillin‐resistant Staphylococcus aureus causes severe disseminated infection and deep venous thrombosis in children: Literature review and recommendations for management
Authors: Nourse Clare , Starr Mike , Munckhof Wendy
Published: June 2007

Abstract:  Community‐acquired methicillin‐resistant Staphylococcus aureus (CA‐MRSA) infection in children is increasingly common and can be associated with dissemination and life‐threatening complications. Empiric therapy for presumed severe Staphylococcus aureus infection should be reviewed. Four children with severe invasive CA‐MRSA infection causing osteomyelitis and pneumonia complicated by pulmonary embolus and deep venous thrombosis are described. The literature is reviewed and recommendations for management are provided.
Trends and future projections of child injury in New South Wales: A tool for advocacy?
Authors: Mitchell Rebecca , Schmertmann Marcia , Sherker Shauna
Published: June 2007

Aims:  To describe the trend of unintentional hospitalised injury in children aged 0–14 years in New South Wales (NSW), Australia during 1993–1994 to 2004–2005 and to estimate future projections of common child injury hospitalisations from 2006 to 2021.

Methods:  NSW hospitalisation data were used to describe injury trends of children aged 14 years or less who were residents of NSW (1993–1994 to 2004–2005). Projected injury‐related hospitalisations of children for 2006–2021 were estimated assuming that the current observed rate of change in childhood injury hospitalisation rates continued to 2021.

Results:  During 1993–1994 to 2004–2005, there were 238 093 injury‐related hospitalisations of children aged 14 years or less in NSW. Assuming the rate of change in injury hospitalisation observed between 1993–1994 and 2004–2005 continued into the future, the all hospitalised injury incidence rate for children aged 14 years or less is projected to decrease by 1.0% each year to 2021. Injury mechanisms such as burns and scalds, swimming pool non‐fatal drowning and poisoning are all projected to decrease in the future, although not for all age groups. Falls (excluding those from playground equipment) and falls from playground equipment hospitalisations (excluding children less than 1 year) are projected to increase.

Conclusion:  Although the incidence of hospitalisation for some common child‐related injury mechanisms is projected to decrease over the coming years, others are projected to increase. It is possible that advocacy efforts might benefit from using projected injury trends. Co‐ordinated cross‐government action is needed to successfully implement child injury prevention strategies, particularly in the playground environment.
Immunisation practices of paediatric oncologists: An Australasian survey
Authors: Crawford Nigel W , Heath John A , Buttery Jim P
Published: June 2007

Aim:  The aim of this survey was to identify the current practices of paediatric oncologists in Australia and New Zealand regarding the immunisation of children treated for cancer.

Methods:  The survey was a nine‐part questionnaire of current immunisation practices emailed to all paediatric oncologists practising in Australia (nine centres) and New Zealand (three centres) in June 2006.

Results:  Overall response rate was 82% (37 of 45 oncologists). Ninety‐four per cent of respondents would recommend commencing ‘booster’ vaccinations at 6 months post completion of chemotherapy, in keeping with the current guidelines. Seventy‐four per cent would recommend varicella vaccination. Intensity of the chemotherapy treatment was felt to be important, with 97% recommending re‐immunising after a high‐intensity regimen and only 48% after a lower‐intensity regimen. Sixty‐nine per cent stated they would recommend yearly influenza vaccinations for their patients.

Conclusion:  This survey highlights the variability of practice in Australasia; for example, nearly one‐third do not recommend yearly influenza vaccination for their patients. The level of chemotherapy intensity was an important factor for paediatric oncologists in determining whether ‘booster’ vaccinations were recommended. This is an important cancer survivorship issue and review of the evidence‐base and implementation of these guidelines is required.
REVIEW OF LARGE DEEP LIPOMATOUS TUMOURS
Authors: Serpell Jonathan W. , Chen Richard Y. Y.
Published: June 2007

Background:  Lipomatous tumours comprise a range of diagnoses. There are controversies regarding the histopathological diagnosis, nomenclature, diagnostic method, surgical management, roles of radiotherapy and the risk of metastasis, local recurrence and dedifferentiation. This study describes our experience with such tumours.

Methods:  Retrospective review of 224 soft tissue tumours from the Senior Author’s (J. W. S.) database identified 28 patients with deep lipomatous tumours. Clinical features and outcomes were studied with median follow up of 1.5 years.

Results:  Eleven deep lipomas, six deep atypical lipomas, four well‐differentiated (lipoma‐like) liposarcomas, three well‐differentiated liposarcomas and four liposarcomas were studied. Preoperative diagnosis was established by image‐guided core biopsy in 20 patients, excisional biopsy in 6, incisional biopsy in 1 and fine‐needle aspiration in 1. All patients diagnosed with deep lipoma and deep atypical lipoma underwent marginal excision. The median size of the excised tumour was 11 cm. Recurrence occurred in three deep atypical lipomas and one liposarcoma. Dedifferentiation occurred in one deep atypical lipoma, which transformed into a liposarcoma. None had metastasis or died of metastatic malignancy.

Conclusion:  Large deep lipomatous tumours are uncommon and although they do not tend to metastasize, they not infrequently recur locally. Hence their local treatment to prevent local recurrence is important. Key aspects in achieving a complete, but marginal resection of the deep atypical lipoma and the well‐differentiated lipoma‐like liposarcoma is accurate preoperative diagnosis with core biopsy and accurate imaging to assess deep unsuspected extensions of the tumour.
MODIFIED CLASSIFICATION FOR ADENOCARCINOMA OF THE GASTRO‐OESOPHAGEAL JUNCTION
Authors: Shearer Christopher J. , Going James J. , Neilson Lisa J. , Stuart Robert C.
Published: June 2007

Background:  Incidence of the gastro‐oesophageal junction adenocarcinoma is increasing. Siewert’s classification subdivides junctional adenocarcinomas anatomically. Cytokeratin (CK) 7 and 20 immunophenotypes differentiate Barrett’s intestinal metaplasia (IM) from gastric IM. Comparing CK immunostaining with Siewert’s classification may establish tumour origin and influence surgical choice.

Methods:  In this experimental study, 57 patients with gastro‐oesophageal junction adenocarcinoma were subdivided endoscopically into 15 type 1, 26 type 2 and 16 type 3 adenocarcinomas. Representative biopsies were immunostained for CK7 and CK20.

Results:  Intestinal metaplasia was associated with type 1 adenocarcinoma in 12 of 15 patients, 80%; with type 2 in 13 of 26 patients, 50% and type 3 in 6 of 16 patients, 37.5%. All type 1 patients showed Barrett’s CK7/CK20 phenotype within IM; type 2 a mixture: 69% (n = 9) Barrett’s CK7/CK20 and 31% (n = 4) gastric CK7/CK20 whereas type 3 patients had a gastric CK7/CK20 pattern in 83% (n = 5). Immunostaining within the adenocarcinoma was variable.

Conclusion:  Siewert’s type 1 adenocarcinomas express Barrett’s CK7/CK20 pattern, type 3 a gastric CK7/CK20 pattern and type 2 tumours a mixture of Barrett’s and gastric CK7/CK20 patterns within associated IM. CK immunostaining may refine Siewert’s classification into oesophageal type 1 or gastric type 2 adenocarcinoma with IM.
SIX‐YEAR PROSPECTIVE ANALYSIS OF THE RECTAL BLEEDING CLINIC AT THE QUEEN ELIZABETH HOSPITAL, ADELAIDE, SOUTH AUSTRALIA
Authors: Lee Jen S. J. , Rieger Nicholas A , Stephens Jacqueline H , Hewett Peter J , Rodda David J , Lawrence Matthew J
Published: June 2007

Background:  One‐stop rectal bleeding clinics (RBC) are designed to diagnose and treat colorectal diseases that present with rectal bleeding. The Queen Elizabeth Hospital RBC is an open access clinic and is unique in South Australia. It offers flexible sigmoidoscopy and facilities for treating common anorectal conditions.

Methods:  Data of all patients presenting to the RBC were prospectively recorded into a database. Data were collected on the patient details, presentation, medical history, physical examination, treatment and intended follow‐up.

Results:  A total of 1539 cases was seen in the clinic between March 2000 and February 2006. Flexible sigmoidoscopy was carried out in 1145 cases (75.03%). Banding or injection of haemorrhoids was carried out in 383 cases. A total of 590 patients was referred for colonoscopy and of these, 27 were diagnosed with colorectal adenocarcinoma or squamous cell cancer of the anus. Most of these patients were more than 50 years old (26 of 27; 96.30%) and had associated symptoms, such as weight loss or altered bowel habit with their rectal bleeding (23 of 27; 85.19%).

Conclusion:  Rectal bleeding clinics can facilitate early diagnosis of colorectal malignancy and can also provide a ‘one‐stop shop’ for treating benign anorectal conditions.
SIMPLE ENDOSCOPIC TECHNIQUE FOR RETRIEVING A LONG FOREIGN BODY FROM THE STOMACH
Authors: Beldholm Bernard R. , Lee Alice U.
Published: June 2007

Background:  Foreign body ingestion occurs frequently and is a common problem confronting the general surgeon or gastroenterologist. Most foreign bodies pass spontaneously, but long items such as forks and spoons are unable to pass through the duodenum. These foreign bodies present a unique challenge for the endoscopist as they tend to T‐bone at the gastro‐oesophageal junction, making it technically very difficult to remove.

Methods:  We prevent a case of a young woman ingesting a spoon.

Results:  By using a single channel gastroscope, snare and altering the position of the operating table we were able to extract the long foreign body.

Conclusion:  We describe an alternate, new technique that may help avoid a laparotomy in a patient presenting after ingestion of a retained gastric foreign body.
15‐YEAR AUDIT OF POST‐TONSILLECTOMY HAEMORRHAGE AT DUNEDIN HOSPITAL
Authors: Macassey Emily A. , Baguley Campbell , Dawes Patrick , Gray Andrew
Published: June 2007

Post‐tonsillectomy haemorrhage is a significant complication because of its frequency and consequences. Increases in post‐tonsillectomy haemorrhage prevalence have been reported. There is a controversy about whether increasing the use of diathermy techniques or anti‐platelet aggregation effects of analgesia could have caused this increase. We carried out an audit of post‐tonsillectomy haemorrhage and examined the rates of readmission for bleeding during the period 1990–2004. We also recorded the surgical technique used and the use of perioperative non‐steroidal anti‐inflammatory drugs and corticosteroids. During this period there has been a significant increase in post‐tonsillectomy haemorrhage with an average annual increase of 15.3% (P < 0.0001, 95% confidence interval 8.5–22.5%). The increase is coincidental with the change‐over to predominant diathermy technique and a routine use of postoperative non‐steroidal anti‐inflammatory drugs and steroids.
Rapid turnover of DOC in temperate forests accounts for increased CO2 production at elevated temperatures
Authors: Bengtson Per , Bengtsson Göran
Published: June 2007

The evidence for the contribution of soil warming to changes in atmospheric CO2 concentrations and carbon stocks of temperate forest ecosystems is equivocal. Here, we use data from a beech/oak forest on concentrations and stable isotope ratios of dissolved organic carbon (DOC), phosphate buffer‐extractable organic carbon, soil organic carbon (SOC), respiration and microbial gross assimilation of N to show that respired soil carbon originated from DOC. However, the respiration was not dependent on the DOC concentration but exceeded the daily DOC pool three to four times, suggesting that DOC was turned over several times per day. A mass flow model helped to calculate that a maximum of 40% of the daily DOC production was derived from SOC and to demonstrate that degradation of SOC is limiting respiration of DOC. The carbon flow model on SOC, DOC, microbial C mobilization/immobilization and respiration is linked by temperature‐dependent microbial and enzyme activity to global warming effects of CO2 emitted to the atmosphere.
Tree diversity reduces herbivory by forest insects
Authors: Jactel Hervé , Brockerhoff Eckehard G.
Published: June 2007

Biodiversity loss from plant communities is often acknowledged to affect primary production but little is known about effects on herbivores. We conducted a meta‐analysis of a worldwide data set of 119 studies to compare herbivory in single‐species and mixed forests. This showed a significant reduction of herbivory in more diverse forests but this varied with the host specificity of insects. In diverse forests, herbivory by oligophagous species was virtually always reduced, whereas the response of polyphagous species was variable. Further analyses revealed that the composition of tree mixtures may be more important than species richnessper sebecause diversity effects on herbivory were greater when mixed forests comprised taxonomically more distant tree species, and when the proportion of non‐host trees was greater than that of host trees. These findings provide new support for the role of biodiversity in ecosystem functioning across trophic levels.
Stochasticity generates an evolutionary instability for infectious disease
Authors: Read Jonathan M. , Keeling Matt J.
Published: June 2007

Traditional models of disease evolution are based upon the deterministic competition between strains that confer complete cross‐immunity, and predict the selection of strains with higher basic reproductive ratios (R0). In contrast, evolution in a stochastic setting is determined by a complex mixture of influences. Here, to isolate the impact of stochasticity, we constrain all competing strains to have an equal basic reproductive ratio – thereby eliminating deterministic selection. The resulting stochastic models predict an evolutionary unstable strategy, which separates a region favouring the evolution of rapid‐transmission (acute) strains from one favouring persistent (chronic) strains. We find this to be a generic phenomenon with strain evolution consistently driven towards extremes of epidemiological behaviour. Even in the absence of an equalR0constraint, such stochastic selective pressures operate in addition to standard deterministic selection and will therefore influence the evolutionary behaviour of disease in all scenarios.
Determinants of Human Rights Attitudes and Behavior: A Comparison and Integration of Psychological Perspectives
Authors: Cohrs J. Christopher , Maes Jürgen , Moschner Barbara , Kielmann Sven
Published: June 2007

Following several political‐psychological approaches, the present research analyzed whether orientations toward human rights are a function of right‐wing authoritarianism (RWA), social dominance orientation (SDO), basic human values in the sense of Schwartz (1992), and political ideology. Three dimensions of human rights attitudes (endorsement, restriction, and enforcement) were differentiated from human rights knowledge and behavior. In a time‐lagged Internet survey (N = 479), using structural equation modeling, RWA, universalism and power values, and political ideology (measured at Time 1) differentially predicted dimensions of human rights attitudes (measured at Time 2 five months later). RWA and universalism values also predicted self‐reported human rights behavior, with the effects mediated through human rights endorsement. Human rights knowledge also predicted behavior. The psychological roots of positive and negative orientations toward human rights, consequences for human rights education, and the particular role of military enforcement of human rights are discussed.
Personality Traits, Partisan Attitudes, and Voting Behavior. Evidence from Germany
Authors: Schoen Harald , Schumann Siegfried
Published: June 2007

Political psychology has paid rather little attention to personality traits when explaining political attitudes and political behavior in mass publics. The present paper argues that personality traits contribute to our understanding of political attitude formation and decision making of ordinary citizens. Based on the Five Factor Model of Personality, we state hypotheses regarding the effects of personality traits on partisan attitudes and vote choice in Germany. We test the hypotheses using survey data obtained from a random sample of the Germans eligible to vote. The evidence confirms that personality traits indirectly affect partisan attitudes and voting behavior in Germany in predictable ways even after controlling for sociodemographic characteristics. More specifically,Opennessmakes citizens more inclined to support parties endorsing social liberalism whereas low scores onConscientiousnessincrease the likelihood of liking and voting for parties subscribing to economic or social liberalism as do high levels onAgreeableness. High levels ofNeuroticismappear to promote support for parties that offer shelter against material or cultural challenges.
Schwa and the phonotactics of RP English
Authors: Heselwood Barry
Published: June 2007

In this paper it is argued that the phonotactics of RP English1should be seen in terms of the arrangement of consonants around a full vowel nucleus, and that schwa has a pivotal role in facilitating such arrangements but is not itself distinctive in the vowel system.2Two types of function are identified for schwa: anaptyctic (e.g.today, abbot), and positional (e.g.support, lotus). Because schwa‐syllables are bound and their vocalic content predictable, there is no justification for setting them up as phonotactic domains. In order that their consonantal content can be put into phonotactic relation with a full vowel, a unit of distribution called a ‘phonotactic group’ is proposed.3
THE IMPACTS OF TRANSPORTATION INFRASTRUCTURE ON PROPERTY VALUES: A HIGHER‐ORDER SPATIAL ECONOMETRICS APPROACH
Authors: Cohen Jeffrey P. , Paul Catherine Morrison
Published: June 2007

ABSTRACT We evaluate the impacts of enhanced transportation systems on property values for U.S. manufacturing firms, allowing for higher‐order spatial error correlation. We use a state‐level model of production cost and input demand that recognizes the productive contribution of public transportation infrastructure stocks. Our findings include significant impacts on property shadow values and input composition from both public highway and airport investment. We also find that these effects have a spatial dimension that depends on the proximity of the transport system; at least one and as many as three spatial error lags are significant in our estimating equations. Further, recognizing production growth from transportation system improvements augments the associated incentives for private capital investment.
SOME EVIDENCE THAT WOMEN ARE MORE MOBILE THAN MEN: GENDER DIFFERENCES IN U.K. GRADUATE MIGRATION BEHAVIOR
Authors: Faggian Alessandra , McCann Philip , Sheppard Stephen
Published: June 2007

ABSTRACT In this paper we employ dichotomous, multinomial and conditional logit models to analyze the employment‐migration behavior of some 380,000 U.K. university graduates. By controlling for a range of variables related to human capital acquisition and local economic conditions, we are able to distinguish between different types of sequential migration behavior from domicile to higher education and on to employment. Our findings indicate that U.K. female graduates are generally more migratory than male graduates. We suggest that the explanation for this result lies in the fact that migration can be used as a partial compensation mechanism for gender bias in the labor market.
THE IMMIGRATION SURPLUS REVISITED IN A GENERAL EQUILIBRIUM MODEL WITH ENDOGENOUS GROWTH*
Authors: Drinkwater Stephen , Levine Paul , Lotti Emanuela , Pearlman Joseph
Published: June 2007

ABSTRACT We revisit the influential work of Borjas (1995) on the economic gain to the host population from immigration—“the immigration surplus.” We develop his analysis by using a general equilibrium endogenous growth model with endogenous capital and several sectors, including an R&D sector driving growth. Skilled immigration leads to a bigger R&D sector share resulting in higher long‐term growth. If skilled labor and physical capital are complements, this growth gain increases. Growth effects on the immigration surplus dominate the purely static effects of Borjas, but are not sufficient to eliminate the emergence of losers (skilled natives) within the host population.
Diet and prey profiles of three sympatric large carnivores in Bandipur Tiger Reserve, India
Authors: Andheria A. P. , Karanth K. U. , Kumar N. S.
Published: June 2007

We conducted a field study of diets of three sympatric large carnivores, the tiger Panthera tigris, the leopard Panthera pardus and the dhole Cuon alpinus in Bandipur Tiger Reserve, India, based on analyses of 381, 111 and 181 scats, respectively. The frequency of occurrence of prey items in scats was converted to relative biomass and number of prey consumed using regression equations based on earlier feeding trials. The results showed that although these predators kill ∼11–15 species of vertebrate prey, relatively abundant ungulate species provide 88–97% of biomass consumed by them. Although the dietary niche overlap among the three species was high (Pianka's index of 0.75–0.93), some specialized predation was observed. The largest ungulates, gaur Bos gaurus and sambar Cervus unicolor, provided 73% of biomass consumed by tigers, whereas medium‐sized chital Axis axis and wild pig Sus scrofa formed 65 and 83% of the biomass intake of leopards and dholes, respectively. In terms of the relative numbers of prey animals killed by the three predators, chital, which is the most abundant prey species, dominated their diets (tiger=33%, leopard=39% and dhole=73%). The results of the study, in conjunction with earlier work, support the prediction that abundance of ungulate prey species, as well as their availability in different size classes, are both critical factors that facilitate sympatry among the three predators.
A novel PIP2 binding of εPKC and its contribution to the neurite induction ability1
Authors: Shirai Yasuhito , Murakami Takuya , Kuramasu Maho , Iijima Leo , Saito Naoaki
Published: June 2007

Protein kinase C‐ε (εPKC) induces neurite outgrowth in neuroblastoma cells but molecular mechanism of the εPKC‐induced neurite outgrowth is not fully understood. Therefore, we investigated the ability of phosphatidylinositol 4,5‐bisphosphate (PIP2) binding of εPKC and its correlation with the neurite extension. We found that full length εPKC bound to PIP2 in a 12‐ο‐tetradecanoylphorbol‐13‐acetate dependent manner, while the regulatory domain of εPKC (εRD) bound to PIP2 without any stimulation. To identify the PIP2 binding region, we made mutants lacking several regions from εRD, and examined their PIP2 binding activity. The mutants lacking variable region 1 (V1) bound to PIP2 stronger than intact εRD, while the mutants lacking pseudo‐substrate or common region 1 (C1) lost the binding. The PIP2 binding ability of the V3‐deleted mutant was weakened. Those PIP2 bindings of εPKC, εRD and the mutants well correlated to their neurite induction ability. In addition, a chimera of pleckstrin homology domain of phospholipase Cδ and the V3 region of εPKC revealed that PIP2 binding domain and the V3 region are sufficient for the neurite induction, and a first 16 amino acids in the V3 region was important for neurite extension. In conclusion, εPKC directly binds to PIP2 mainly through pseudo‐substrate and common region 1, contributing to the neurite induction activity.
Blood glucose control in critical care patients – a review of the literature
Authors: Parsons Penny , Watkinson Peter
Published: June 2007

The role of hyperglycaemia in critical illness, and its corresponding treatment, has been an area of controversy, fuelled by conflicting research findings. The aims of this study were to critically evaluate the literature and present an historical review of the sequence of published papers relating to blood glucose control in critical care. Their subsequent impact together with the implications for patient care is discussed. This article is based on a systematic review of papers relating to glycaemic control in critical care patients. The review was conducted using the MedLine, CINAHL and EMBASE databases using key search terms (details of the search terms can be found after the conclusion of the paper) for the period 1950–2006. The searches resulted in 4863 papers being screened for relevance to the historic progression of glycaemic management in critical care patients, by title and then abstract. Of these, 209 were accessed, and their reference lists were snowballed for further papers. Papers that were repeatedly quoted throughout the literature and were therefore considered important in the historical development of accepted critical care practice were finally subjected to rigorous appraisal. These totalled 91 papers and included 18 randomized controlled trials, an additional 28 research papers, 25 editorials and 20 reviews. This critical evaluation of published work indicates that the evidence for the benefit of this therapy may not be as compelling as previously indicated, and its widespread use may have been premature. From a nursing perspective, this demonstrates the importance of maintaining a questioning attitude to new therapies and reviewing best practice in the light of evolving evidence.
Reflection on practice: an intubated patient suffering panic attacks
Authors: Davies Debbie
Published: June 2007

Panic attacks and respiratory disease have been shown to have probable links; which one is the precursor to the other is unknown. However, what is known is that there is a correlation between high serum carbon dioxide and lactate levels, which are suffocation indicators, and panic attacks. Females are at a higher risk of suffering panic attacks than men, as they have been shown to have a lower tolerance of suffocation indicators. The aim of this paper is to review the relevance of panic attacks within the intensive care unit setting, where a significant number of patients with respiratory disease have an oral endotracheal tube, which limits communication and may add to the feeling of panic. Using a reflective model, I revisited the actual scenario and consider the series of events as I reflect in action, and at the conclusion of the situation, I reflect on action. The results show that suffering from panic attacks did not inhibit the patient with weaning from the ventilator. Effective communication between the patient and myself led to recognition of the problem, for the correct treatment to be being given, and enabling subsequent extubation. In conclusion, once the link is made of the likelihood of a patient with respiratory disease being prone to panic attacks, the nurse can communicate with the patient or family to establish whether the patient has a panic disorder. The treatment of a regular benzodiazepine, such as diazepam, and constant reassurance from the nurse can then be given to the patient to minimize the symptoms. Reducing the effects of panic attacks can decrease the distress experienced by the patient and improve the clinical picture to facilitate extubation.
Ethical Issues in Dialysis Aaron Spital, Series Editor: Responding to Requests for Dialysis for Severely Demented and Brain Injured Patients
Authors: Spike Jeffrey P.
Published: June 2007

Nephrologists, like all physicians, need to offer their patients all reasonable treatment options, but only the reasonable options. When dialysis is (or is not) a reasonable option is an important ethical issue. The justification for dialysis, like any life‐sustaining treatment, is that it prolongs life for a patient who either wishes to live or, if cognitively impaired, would (in the opinion of others) likely benefit from extending their life. This article focuses on patients with advanced dementia or severe and irreversible brain injury who are no longer capable of enjoying life, and hence gain no benefit from dialysis. I present guidelines for withholding and withdrawing dialysis and offer suggestions designed to help nephrologists avoid causing harm when the patient’s family demands that dialysis be performed.