bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravenous TAT-GDNF Is Protective After Focal Cerebral Ischemia in Mice
Authors: Kilic Ülkan , Kilic Ertugrul , Dietz Gunnar P.H. , Bähr Mathias
Published: May 2003

Background and Purpose—

Delivery of therapeutic proteins into tissues and across the blood-brain barrier is severely limited by their size and biochemical properties. The 11-amino acid human immunodeficiency virus TAT protein transduction domain is able to cross cell membranes and the blood-brain barrier, even when coupled with larger peptides. The present studies were done to evaluate whether TAT–glial line-derived neurotrophic factor (GDNF) fusion protein is protective in focal cerebral ischemia.

Methods—

Anesthetized male C57BL/6j mice were submitted to intraluminal thread occlusion of the middle cerebral artery. Reperfusion was initiated 30 minutes later by thread retraction. Laser Doppler flow was monitored during the experiments. TAT-GDNF, TAT-GFP (0.6 nmol each), or vehicle was intravenously applied over 10 minutes immediately after reperfusion. After 3 days (30 minutes of ischemia), animals were reanesthetized and decapitated. Brain injury was evaluated by histochemical stainings.

Results—

Immunocytochemical experiments confirmed the presence of TAT-GDNF protein in the brains of fusion protein–treated nonischemic control animals 3 to 4 hours after TAT fusion protein delivery. TAT-GDNF significantly reduced the number of caspase-3–immunoreactive and DNA-fragmented cells and increased the number of viable neurons in the striatum, where disseminated tissue injury was observed, compared with TAT-GFP– or vehicle-treated animals.

Conclusions—

Our results demonstrate that TAT fusion proteins are powerful tools for the treatment of focal ischemia when delivered both before and after an ischemic insult. This approach may be of clinical interest because such fusion proteins can be intravenously applied and reach the ischemic brain regions. This approach may therefore offer new perspectives for future strategies in stroke therapy.
Pilot Dose-Escalation Study of Caffeine Plus Ethanol (Caffeinol) in Acute Ischemic Stroke
Authors: Piriyawat Paisith , Labiche Lise A. , Burgin W. Scott , Aronowski Jaroslaw A. , Grotta James C.
Published: May 2003

Background and Purpose—

In animal models, the combination of caffeine and ethanol (caffeinol) provides robust neuroprotection at blood levels that should be easily and safely achieved in humans. This study was designed to determine the safety and tolerability of ascending doses of this combination in stroke patients.

Methods—

This Food and Drug Administration–approved open-label, single-arm, dose-escalation study had 3 original dose groups: group 1, caffeine 6 mg/kg plus ethanol 0.2 g/kg; groups 2 and 3, incremental increases of caffeine and ethanol by 2 mg/kg and 0.2 g/kg, respectively. Intravenous thrombolysis was encouraged if patients qualified. Drug was started within 6 hours of stroke onset, and blood levels of caffeine and ethanol were drawn at baseline and end of infusion. The target blood caffeine and ethanol ranges were 8 to 10 μg/mL and 30 to 50 mg/dL, respectively. Clinical outcome measurements included the National Institutes of Health Stroke Scale at the end of infusion, at 24 hours, and at discharge. Potential complications from caffeine and ethanol were recorded. Cases were reviewed by an independent stroke neurologist for safety.

Results—

A total of 23 patients were recruited. Target blood caffeine and ethanol levels were reached in 0 of the 4 patients in the first group. The second dose group (caffeine 8 mg/kg plus ethanol 0.4 g/kg) included 8 patients. The median end-of-infusion caffeine and ethanol levels were within the desired target ranges. Two days after infusion, 1 patient in this group with preexisting cardiac disease and end-of-infusion caffeine and ethanol levels of 10.7 μg/mL and 69 mg/dL developed reversible congestive heart failure and required transfer to an intensive care unit. The original third dose group was canceled given achievement of target blood caffeine and ethanol levels in group 2. However, 3 new dose groups were created in an attempt to minimize the dose of ethanol. Although blood levels were proportional to dose, none of these new dose groups provided optimal blood levels. Congestive heart failure occurred in 1 other patient with previously asymptomatic cardiomyopathy. No other side effects were noted. Concomitant thrombolytic therapy was given in 8 patients, 1 of whom died of intracerebral hemorrhage.

Conclusions—

Caffeinol alone or combined with intravenous tissue plasminogen activator can be administered safely. Caffeine 8 mg/kg plus ethanol 0.4 g/kg produces target caffeine and ethanol levels of 8 to 10 μg/mL and 30 to 50 mg/dL, respectively. A randomized, placebo-controlled trial is needed to determine the neuroprotective effect of this combination.
ATP-Sensitive Potassium Channels Mediate Dilatation of Basilar Artery in Response to Intracellular Acidification In Vivo
Authors: Santa Naohiko , Kitazono Takanari , Ago Tetsuro , Ooboshi Hiroaki , Kamouchi Masahiro , Wakisaka Masanori , Ibayashi Setsuro , Iida Mitsuo
Published: May 2003

Background and Purpose—

During cerebral ischemia, both hypoxia and hypercapnia appear to produce marked dilatation of the cerebral arteries. Hypercapnia and hypoxia may be accompanied by extracellular and intracellular acidosis, which is another potent dilator of cerebral arteries. However, the precise mechanism by which acidosis produces dilatation of the cerebral arteries is not fully understood. The objective of the present study was to examine the mechanisms by which intracellular acidosis produces dilatation of the basilar artery in vivo.

Methods—

Using a cranial window in anesthetized rats, we examined responses of the basilar artery to sodium propionate, which was used to cause intracellular acidosis specifically. Expression of subunits of potassium channels was determined by reverse transcription and polymerase chain reaction (RT-PCR).

Results—

Topical application of propionate increased diameter of the basilar artery in a concentration-related manner. Propionate-induced dilatation of the artery was attenuated by glibenclamide, an inhibitor of ATP-sensitive potassium channels. However, inhibitors of nitric oxide synthase (
N
G
-nitro-
l
-arginine), large-conductance calcium-activated potassium channels (iberiotoxin), and cyclooxygenase (indomethacin) did not affect the vasodilatation. Expression of mRNA for SUR2B and Kir6.1 was detected, with the use of RT-PCR, in the cultured basilar arterial muscle cells.

Conclusions—

The findings suggest that intracellular acidification may produce dilatation of the basilar artery through activation of ATP-sensitive potassium channels in vivo. Kir6.1/SUR2B may be the major potassium channels that mediate propionate-induced dilatation of the artery.
In Vivo Gene Transfer of Inducible Nitric Oxide Synthase to Carotid Arteries From Hypercholesterolemic Rabbits
Authors: Zanetti Michela , d’Uscio Livius V. , Kovesdi Imre , Katusic Zvonimir S. , O’Brien Timothy
Published: May 2003

Background and Purpose—

Hypercholesterolemia is associated with endothelial dysfunction. Inducible nitric oxide synthase (iNOS) is upregulated in atherosclerotic vessels. However, its role in the regulation of vascular function is not completely understood. We examined the effect of adenovirus-mediated gene transfer of iNOS to the hypercholesterolemic rabbit carotid artery in vivo.

Methods—

Rabbits were fed a high-cholesterol or chow diet for 10 weeks. Two doses (1×10
8
and 1×10
9
plaque-forming units [pfu]/mL) of adenoviral vectors encoding iNOS (AdiNOS) or β-galactosidase (Adβgal) were luminally delivered to the carotid arteries from chow- and cholesterol-fed animals. Vascular reactivity and superoxide levels were assessed in Adβgal- and AdiNOS-transduced vessels from chow- and cholesterol-fed animals after 3 days.

Results—

Endothelium-dependent vasorelaxation was impaired in the carotid artery from cholesterol-fed animals. In AdiNOS-transduced arteries, transgene expression was demonstrated by positive immunostaining in the endothelium. Transduction with low-dose (1×10
8
pfu/mL) AdiNOS did not affect vascular reactivity in arteries from chow- and cholesterol-fed animals. In contrast, high-dose (1×10
9
pfu/mL) AdiNOS significantly reduced endothelium-dependent relaxation in vessels from cholesterol- but not chow-fed rabbits. After both low- and high-dose iNOS gene transfer, levels of O
2
·
−
were significantly (
P
<0.05) elevated in carotid arteries from cholesterol-fed animals. Incubation with an O
2
·
−
scavenger did not reverse vascular dysfunction in these arteries.

Conclusions—

Adenoviral-mediated overexpression of iNOS results in increased production of O
2
·
−
in carotid arteries from cholesterol- but not chow-fed animals. High-dose AdiNOS gene transfer is associated with reduced endothelium-dependent and -independent relaxation in vessels from cholesterol-fed animals.
Evaluating the Context-Dependent Effect of Family History of Stroke in a Genome Scan for Hypertension
Authors: Morrison Alanna C. , Brown Andrew , Kardia Sharon L.R. , Turner Stephen T. , Boerwinkle Eric
Published: May 2003

Background and Purpose—

Hypertension is an important risk factor for stroke, and the 2 diseases may share susceptibility genes in common. We sought to identify genomic regions influencing susceptibility to both hypertension and stroke.

Subjects and Methods—

Genome-wide linkage scans were performed in samples of 338 white and 265 black hypertensive sibships recruited by the Genetic Epidemiology Network of Arteriopathy Study of the NHLBI Family Blood Pressure Program (FBPP). The hypertensive sibships were stratified by positive (+FH) or negative (−FH) family history of stroke. Genome-wide scans were repeated in each stratum, and the results were compared within each ethnic group by a regression-based analysis of heterogeneity.

Results—

In whites, the best evidence for linkage was found on chromosome 16 in the unstratified sample of hypertensive sibpairs (logarithm of odds [LOD]=1.85 at 71 cM). In blacks, the best evidence for linkage was found on chromosome 2 in the unstratified sample of hypertensive sibpairs (LOD=1.95 at 230 cM). Additional evidence for linkage (LOD ≥1.5) was observed among white hypertensive sibpairs with a −FH on chromosome 13 and among black hypertensive sibpairs with a +FH of stroke on chromosome 19.

Conclusions—

Significant evidence for linkage heterogeneity among hypertensive sibpairs stratified by family history of stroke suggests the presence of genes influencing susceptibility to both hypertension and stroke on chromosomes 13 (whites) and 19 (blacks). Although no significant evidence of heterogeneity was observed on chromosome 16 in whites and chromosome 2 in blacks, these chromosomes do provide evidence of linkage to hypertension.
Prediction of Hyperperfusion After Carotid Endarterectomy by Brain SPECT Analysis With Semiquantitative Statistical Mapping Method
Authors: Hosoda Kohkichi , Kawaguchi Tetsuro , Ishii Kazunari , Minoshima Satoshi , Shibata Yuji , Iwakura Masaki , Ishiguro Shigeo , Kohmura Eiji
Published: May 2003

Background and Purpose—

Hyperperfusion syndrome is a rare but disastrous complication after carotid endarterectomy (CEA). The aim of this study was to investigate the relationship between preoperative cerebral blood flow (CBF) abnormalities and postoperative hyperperfusion through the use of statistical brain mapping analysis.

Methods—

For 41 patients with unilateral carotid stenosis ≥70%, CBF and cerebral vasoreactivity (CVR) were investigated with resting and acetazolamide-challenge single photon emission CT before CEA. CBF 1 day after CEA was also measured. Three-dimensional stereotactic surface projection (3D-SSP) analysis of CBF changes was performed by use of a control database of 20 subjects.

Results—

Patients with reduced CVR (CVR <10%, n=15) were categorized into 2 groups based on the severity of CBF reduction relative to the control database by 3D-SSP analysis without normalization: type I (ipsilateral CBF decrease <20%, n=8) and type II (ipsilateral CBF decrease ≥20%, n=7). With thalamic normalization, the patients were also categorized into 2 groups: type A (ipsilateral
Z
score ≤2, n=10) and type B (ipsilateral
Z
score >2, n=5). Severe CBF reduction (≥20% or
Z
score >2) was significantly associated with postoperative hyperperfusion (CBF increase ≥100%). However, 3D-SSP with thalamic normalization (
Z
score) demonstrated a higher predictive value (80%) and specificity (91%) for hyperperfusion than 3D-SSP without normalization (percent reduction) (57% and 73%, respectively). No patients with normal CVR (CVR ≥10%, n=26) demonstrated postoperative hyperperfusion.

Conclusions—

Objective evaluation of abnormalities of CBF and CVR with 3D-SSP could identify patients at risk for postoperative hyperperfusion.
Elastin Polymorphism Haplotype and Intracranial Aneurysms Are Not Associated in Central Europe
Authors: Hofer Anne , Hermans Marcella , Kubassek Nina , Sitzer Matthias , Funke Harald , Stögbauer Florian , Ivaskevicius Vytautas , Oldenburg Johannes , Burtscher Johannes , Knopp Ulrich , Schoch Beate , Wanke Isabel , Hübner Felix , Deinsberger Wolfgang , Meyer Bernhard , Boecher-Schwarz Hans , Poewe Werner , Raabe Andreas , Steinmetz Helmuth , Auburger Georg
Published: May 2003

Background and Purpose—

The occurrence of intracranial aneurysms and of aneurysmal subarachnoid hemorrhage are influenced by genetic factors. Recent genomic studies in Japan have defined 3 chromosomal loci and 1 haplotype of elastin polymorphisms as important risk factors, both for affected sib pairs and sporadic patients.

Methods—

We have genotyped 2 single nucleotide polymorphisms in the elastin gene and evaluated their allelic association with intracranial aneurysm in a Central European sample of 30 familial and 175 sporadic patients and 235 population controls.

Results—

We found no allelic association between this elastin polymorphism haplotype and intracranial aneurysm.

Conclusion—

Our data probably reflect increased genetic heterogeneity of intracranial aneurysm in Europe compared with Japan.
Increased Risk of Cognitive Impairment 3 Months After Mild to Moderate First-Ever Stroke
Authors: Srikanth Velandai K. , Thrift Amanda G. , Saling Michael M. , Anderson Jacqueline F.I. , Dewey Helen M. , Macdonell Richard A.L. , Donnan Geoffrey A.
Published: May 2003

Background and Purpose—

Results of hospital-based studies indicate a high risk of cognitive impairment 3 months after stroke. There are no comprehensive data on this issue from prospective community-based studies comparing first-ever stroke patients with stroke-free subjects.

Methods—

We administered a comprehensive neuropsychological battery to 99 community-based nonaphasic survivors of first-ever stroke at 3 months and 99 age- and sex-matched (1:1) stroke-free individuals. Domain-specific cognitive deficits were identified by blinded neuropsychological consensus.

Methods—

Stroke patients were more likely to suffer any cognitive impairment (relative risk [RR], 1.5; 95% CI, 1.1 to 2.1) attributable mainly to a greater risk of single-domain cognitive impairment (RR, 2.8; 95% CI, 1.5 to 5.3) but not multiple-domain cognitive impairment (RR, 1.2; 95% CI, 0.8 to 1.9).

Conclusions—

In this community-based study, a first-ever stroke of mild to moderate severity was associated with a significant risk of cognitive impairment at 3 months, even in the absence of clinical aphasia. This was due primarily to an increased risk of solitary deficits rather than generalized deficits.
EURIPIDES, MEDEA 131-213
Authors:   Willink
Published: May 2003

The Parodos of Medea, with the following musical exchanges between Chorus, Medea (offstage) and Nurse, has some unsatisfactory features in the manuscripts and in editions, for which some new remedies are proposed. Already in the Entry-verses (131-8) the detail of the text has long been controversial, on grounds partly linguistic, partly metrical. Later, at 160 Medea is heard invoking "Themis and Artemis", in words directly referred to by the Nurse at 168-9 as addressed to "Themis and Zeus", and less directly at 208-9 by the Chorus as addressed to "Themis (wife) of Zeus". The apparently irrelevant '′Αρτεμι in 160 has been variously emended by Weil and others. A number of other points of interest (especially of metre) are discussed in passing. But the most important single proposal is a transposition putting lines 160-72 after 173-203; thus on the one hand making the antistrophe 173-83 directly sequential to the strophe 148-59, and on the other hand making the concluding choral epode (204-13: "I heard . . .") directly responsive to the Nurse's question at 168-70 ("Do you hear . . .?"). The Nurse's sinister forecast at 171-2 becomes her parting words, as she goes into the house (we shall not see her again) to fetch her mistress.
DIVINE TYRANNY AND PUBLIC HUMILIATION: A SUGGESTION FOR THE INTERPRETATION OF THE LYDIAN AND PHRYGIAN CONFESSION INSCRIPTIONS
Authors: Schnabel Eckhard
Published: May 2003

The Lydian and Phrygian confession inscriptions dating mostly to the 2nd and 3rd centuries C.E. have provoked less discussion than one would expect. This paper focuses on what was probably the main reason for the pressure to confess sins publicly. A major cause for public confession seems to have been the perceived necessity to reinforce the control of the local god over his or her devotees. The impetus may have been the spreading of the Christian faith in Lydia and Phrygia. It is suggested that the local religious functionaries may have responded by heightening the people's awe concerning the power of the gods, requiring public confessions of specific sins that highlight the frightful power of the gods over all aspects of life, and by requiring the erection of steles in the hope of establishing the permanent loyalty of the people for the god who ruled over the village.
Nonallergic respiratory morbidity improved along with a decline of traditional air pollution levels: a review
Authors: Heinrich J.
Published: May 2003

The tremendous decline of combustion-derived emissions of traditional air pollutants such as sulphur dioxide (SO2) and total suspended particles (TSP) in Eastern Germany shortly after German reunification in 1990 provided the unique opportunity to study trends of prevalence of respiratory illness along with the improvement of air quality.

The present review focused on the results of two repeated surveys of nonallergic respiratory illness in children living in East Germany. The crude prevalence of respiratory illness such as lifetime bronchitis, otitis media, tonsillitis, frequent colds, and frequent cough decreased during the 1990s in East German children. For two surveys the effect estimates showed consistently statistically significant association of TSP with bronchitis. For SO2statistically significant associations with frequent colds were also consistently found, whereas at least one survey reported higher statistically significant effect estimates for tonsillitis, otitis media, frequent cough and reduced forced vital capacity.

The present study concludes that the prevalence of nonallergic respiratory illness in East German children is associated with sulphur dioxide and total suspended particles and that the improvement of air quality has beneficial effects on respiratory health.
Short-term effects of ambient particles on mortality in the elderly: results from 28 cities in the APHEA2 project
Authors: Aga E. , Samoli E. , Touloumi G. , Anderson H.R. , Cadum E. , Forsberg B. , Goodman P. , Goren A. , Kotesovec F. , Kriz B. , Macarol-Hiti M. , Medina S. , Paldy A. , Schindler C. , Sunyer J. , Tittanen P. , Wojtyniak B. , Zmirou D. , Schwartz J. , Katsouyanni K.
Published: May 2003

Within the framework of the APHEA2 (Air Pollution on Health: a European Approach) project, the effects of ambient particles on mortality among persons ≥65 yrs were investigated.

Daily measurements for particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10) and black smoke (BS), as well as the daily number of deaths among persons ≥65 yrs of age, from 29 European cities, have been collected. Data on other pollutants and meteorological variables, to adjust for confounding effects and data on city characteristics, to investigate potential effect modification, were also recorded. For individual city analysis, generalised additive models extending Poisson regression, using a locally weighted regression (LOESS) smoother to control for seasonal effects, were applied. To combine individual city results and explore effect modification, second stage regression models were applied.

The per cent increase (95% confidence intervals), associated with a 10 µg·m−3increase in PM10, in the elderly daily number of deaths was 0.8% (0.7–0.9%) and the corresponding number for BS was 0.6% (0.5–0.8%). The effect size was modified by the long-term average levels of nitrogen dioxide (higher levels were associated with larger effects), temperature (larger effects were observed in warmer countries), and by the proportion of the elderly in each city (a larger proportion was associated with higher effects).

These results indicate that ambient particles have effects on mortality among the elderly, with relative risks comparable or slightly higher than those observed for total mortality and similar effect modification patterns. The effects among the older persons are of particular importance, since the attributable number of events will be much larger, compared to the number of deaths among the younger population.
Genetic aspects of susceptibility to air pollution: Table 1
Authors: Kleeberger S.R.
Published: May 2003

Inter-individual variation in human responses to air pollutants suggests that some subpopulations are at increased risk, and it is increasingly clear that genetic background is an important susceptibility factor.

Genetically standardised animal models provide useful investigative tools. Linkage analyses using inbred mice identified chromosomal segments (quantitative trait loci (QTL)), with genes controlling susceptibility to the lung inflammatory (chromosome 17), injury (chromosome 11), and hyperpermeability (chromosome 4) responses to ozone (O3) exposure. An immune dysfunction response induced by exposure to sulphate-associated particles is linked to the identical chromosome 17 and 11 QTLs described for O3susceptibility, thus similar genetic mechanisms may be controlling pulmonary responses to these pollutants. Candidate genes within the QTLs on chromosomes 4 and 17 include the toll-like receptor 4 and the pro-inflammatory cytokine, tumour necrosis factor‐α, respectively. Functional analyses strongly support a role for these candidate genes in determining susceptibility to O3and particulates. Because striking linkage homology exists between the human and mouse genomes, candidate susceptibility genes identified in the mouse are likely to aid research aimed at understanding human genetic factors that contribute to differential susceptibility.

To date, no studies have examined the interaction between age and genetic background in the development of air pollution-induced lung disease. However, investigations have suggested an influence of age on genetic susceptibility to lung cancer and other diseases, which indicate that an interaction between age and genetic background may be important in air pollution disease pathogenesis.
Indoor air pollution and respiratory health in the elderly
Authors: Simoni M. , Jaakkola M.S. , Carrozzi L. , Baldacci S. , Di Pede F. , Viegi G.
Published: May 2003

People spend about ≥80–90% of their daily time indoors, elderly people especially at home. Thus, it is important to investigate possible health effects of indoor air pollutants and to consider their contributions to the total human exposure.

This report summarises current knowledge on health effects of three common indoor air pollutants, respirable suspended particles, nitrogen dioxide and environmental tobacco smoke, with focus on the adults and the elderly. Preliminary findings on exposure distributions and health effects of these pollutants in older subjects of two panel studies carried out in Italian general populations will also be reported.

The two indoor pollution studies were performed in the Po Delta area in North Italy (428 subjects and 140 houses investigated) and in Pisa in Central Italy (761 subjects and 282 houses investigated). Individuals aged ≥65 yrs spent a significantly larger number of hours at home than the other age groups both in winter and in summer. A trend of higher occurrence of acute respiratory symptoms in the presence of environmental tobacco smoke was shown in comparison to the unexposed elderly both in winter (31versus29%) and summer (33versus16%). The occurrence of acute respiratory symptoms was consistently higher in relation to the high respirable suspended particles-index exposure compared to low exposure (33versus27% in winter, 27versus21% in summer). Both the presence of environmental tobacco smoke at home and exposure to the high respirable suspended particles-index were associated with a decrease in the mean daily peak expiratory flow.
Comparison of bedside measurement of cardiac output with the thermodilution method and the Fick method in mechanically ventilated patients
Authors: Gonzalez Jésus , Delafosse Christian , Fartoukh Muriel , Capderou André , Straus Christian , Zelter Marc , Derenne Jean-Philippe , Similowski Thomas
Published: May 2003

Introduction

Bedside cardiac output determination is a common preoccupation in the critically ill. All available methods have drawbacks. We wished to re-examine the agreement between cardiac output determined using the thermodilution method (QTTHERM) and cardiac output determined using the metabolic (Fick) method (QTFICK) in patients with extremely severe states, all the more so in the context of changing practices in the management of patients. Indeed, the interchangeability of the methods is a clinically relevant question; for instance, in view of the debate about the risk–benefit balance of right heart catheterization.

Patients and methods

Eighteen mechanically ventilated passive patients with a right heart catheter in place were studied (six women, 12 men; age, 39–84 years; simplified acute physiology scoreII, 39–111). QTTHERM was obtained using a standard procedure. QTFICK was measured from oxygen consumption, carbon dioxide production, and arterial and mixed venous oxygen contents. Forty-nine steady-state pairs of measurements were performed. The data were normalized for repeated measurements, and were tested for correlation and agreement.

Results

The QTFICK value was 5.2 ± 2.0 l/min whereas that of QTTHERM was 5.8 ± 1.9 l/min (R = 0.840, P < 0.0001; mean difference, -0.7 l/min; lower limit of agreement, -2.8 l/min; upper limit of agreement, 1.5 l/min). The agreement was excellent between the two techniques at QTTHERM values <5 l/min but became too loose for clinical interchangeability above this value. Tricuspid regurgitation did not influence the results.

Discussion and conclusions

No gold standard is established to measure cardiac output in critically ill patients. The thermodilution method has known limitations that can lead to inaccuracies. The metabolic method also has potential pitfalls in this context, particularly if there is increased oxygen consumption within the lungs. The concordance between the two methods for low cardiac output values suggests that they can both be relied upon for clinical decision making in this context. Conversely, a high cardiac output value is more difficult to rely on in absolute terms.
Protein-losing enteropathy in patients with Fontan circulation: is it triggered by infection?
Authors: Lenz Dominik , Hambsch Jörg , Schneider Peter , Häusler Hans-Jürgen , Sauer Ursula , Hess John , Tárnok Attila
Published: May 2003

Introduction

Protein-losing enteropathy (PLE) is a recognised complication of the Fontan circulation. Its pathogenesis is not fully understood, however, and it is unclear why its onset occurs months or even years after Fontan surgery.

Patients

We report a 4.5-year-old girl with Fontan circulation who developed PLE almost 1 year after surgery. At the time of onset the patient had rotavirus enteritis and streptococcal tonsillitis. We have reviewed the records of seven other patients with longstanding PLE. In six of these patients we identified infections at the onset of symptoms. None of our patients had evidence of opportunistic infection.

Discussion and conclusion

The immune system of patients with PLE is compromised, but reports on recurrent opportunistic infections are rare. The present observations suggest that infection and inflammation may be associated with the onset of PLE. The mechanism of how infection may trigger PLE warrants further investigation.
Severe sepsis: variation in resource and therapeutic modality use among academic centers
Authors: Yu D Tony , Black Edgar , Sands Kenneth E , Schwartz J Sanford , Hibberd Patricia L , Graman Paul S , Lanken Paul N , Kahn Katherine L , Snydman David R , Parsonnet Jeffrey , Moore Richard , Platt Richard , Bates David W ,   for the Academic Medical Center Consortium Sepsis Project Working Group
Published: May 2003

Background

Treatment of severe sepsis is expensive, often encompassing a number of discretionary modalities. The objective of the present study was to assess intercenter variation in resource and therapeutic modality use in patients with severe sepsis.

Methods

We conducted a prospective cohort study of 1028 adult admissions with severe sepsis from a stratified random sample of patients admitted to eight academic tertiary care centers. The main outcome measures were length of stay (LOS; total LOS and LOS after onset of severe sepsis) and total hospital charges.

Results

The adjusted mean total hospital charges varied from $69 429 to US$237 898 across centers, whereas the adjusted LOS after onset varied from 15.9 days to 24.2 days per admission. Treatments used frequently after the first onset of sepsis among patients with severe sepsis were pulmonary artery catheters (19.4%), ventilator support (21.8%), pressor support (45.8%) and albumin infusion (14.4%). Pulmonary artery catheter use, ventilator support and albumin infusion had moderate variation profiles, varying 3.2-fold to 4.9-fold, whereas the rate of pressor support varied only 1.92-fold across centers. Even after adjusting for age, sex, Charlson comorbidity score, discharge diagnosis-relative group weight, organ dysfunction and service at onset, the odds for using these therapeutic modalities still varied significantly across centers. Failure to start antibiotics within 24 hours was strongly correlated with a higher probability of 28-day mortality (r2 = 0.72).

Conclusion

These data demonstrate moderate but significant variation in resource use and use of technologies in treatment of severe sepsis among academic centers. Delay in antibiotic therapy was associated with worse outcome at the center level.
Gastric intramucosal pH is stable during titration of positive end-expiratory pressure to improve oxygenation in acute respiratory distress syndrome
Authors: Akinci Ibrahim Ozkan , Çakar Nahit , Mutlu Gökhan Mehmet , Tugrul Simru , Ergin Ozcan Perihan , Gitmez Musa , Esen Figen , Telci Lutfi
Published: May 2003

Background

Optimal positive end-expiratory pressure (PEEP) is an important component of adequate mechanical ventilation in acute lung injury and acute respiratory distress syndrome (ARDS). In the present study we tested the effect on gastric intramucosal pH of incremental increases in PEEP level (i.e. PEEP titration) to improve oxygenation in ARDS. Seventeen consecutive patients with ARDS, as defined by consensus criteria, were included in this clinical, prospective study. All patients were haemodynamically stable, and were not receiving vasopressors. From an initial level of 5 cmH2O, PEEP was titrated at 2 cmH2O increments until the partial arterial oxygen tension was 300 mmHg or greater, peak airway pressure was 45 cmH2O or greater, or mean arterial blood pressure decreased by 20% or more of the baseline value. Optimal PEEP was defined as the level of PEEP that achieved the best oxygenation. The maximum PEEP was the highest PEEP level reached during titration in each patient.

Results

Gastric mucosal pH was measured using gastric tonometry at all levels of PEEP. The thermodilution technique was used for measurement of cardiac index. Gastric mucosal pH was similar at baseline and at optimal PEEP levels, but it was slightly reduced at maximum PEEP. Cardiac index and oxygen delivery remained stable at all PEEP levels.

Conclusion

Incremental titration of PEEP based on improvement in oxygenation does not decrease gastric intramucosal perfusion when cardiac output is preserved in patients with ARDS.
Erythropoietin mimics the acute phase response in critical illness
Authors: Elliot John Michael , Virankabutra Tanit , Jones Stephen , Tanudsintum Surasak , Lipkin Graham , Todd Susan , Bion Julian
Published: May 2003

Background

In a prospective observational study, we examined the temporal relationships between serum erythropoietin (EPO) levels, haemoglobin concentration and the inflammatory response in critically ill patients with and without acute renal failure (ARF).

Patients and method

Twnety-five critically ill patients, from general and cardiac intensive care units (ICUs) in a university hospital, were studied. Eight had ARF and 17 had normal or mildly impaired renal function. The comparator group included 82 nonhospitalized patients with normal renal function and varying haemoglobin concentrations. In the patients, levels of haemoglobin, serum EPO, C-reactive protein, IL-1β, IL-6, serum iron, ferritin, vitamin B12 and folate were measured, and Coombs test was performed from ICU admission until discharge or death. Concurrent EPO and haemoglobin levels were measured in the comparator group.

Results

EPO levels were initially high in patients with ARF, falling to normal or low levels by day 3. Thereafter, almost all ICU patients demonstrated normal or low EPO levels despite progressive anaemia. IL-6 exhibited a similar initial pattern, but levels remained elevated during the chronic phase of critical illness. IL-1β was undetectable. Critically ill patients could not be distinguished from nonhospitalized anaemic patients on the basis of EPO levels.

Conclusion

EPO levels are markedly elevated in the initial phase of critical illness with ARF. In the chronic phase of critical illness, EPO levels are the same for patients with and those without ARF, and cannot be distinguished from noncritically ill patients with varying haemoglobin concentrations. Exogenous EPO therapy is unlikely to be effective in the first few days of critical illness.
Acute renal failure from organophospate poisoning: a case of success with haemofiltration
Authors: Agostini Moreno , Bianchin Andrea
Published: May 2003

Severe organophosphate poisoning (OPP) has a high mortality rate. Respiratory and neurological complications are common in OPP. Multiple organ distress syndrome (MODS) and renal impairment are relatively rare but correlated with death. In previous publications, in patients who did not survive OPP, their deaths were due to MODS or acute renal failure. A case of intentional ingestion of an organophosphate with renal and multiple organ complications is described. In addition to the standard atropine/oxime regimen, continuous venous-venous haemofiltration (CVVH) therapy was started; the patient survived this intoxication. The pathogenesis of renal injury by OPP is unclear and more insight is required. In our experience, CVVH can be a valid therapy, considering in particular the toxicokinetics of the organophosphate.
Ethical Issues Regarding Human Cloning: a nursing perspective
Authors: Dinç Leyla
Published: May 2003

Advances in cloning technology and successful cloning experiments in animals have raised concerns about the possibility of human cloning in recent years. Despite many objections, this is not only a possibility but also a reality. Human cloning is a scientific revolution. However, it also introduces the potential for physical and psychosocial harm to human beings. From this point of view, it raises profound ethical, social and health related concerns. Human cloning would have an impact on the practice of nursing because it could result in the creation of new physiological and psychosocial conditions that would require nursing care. The nursing profession must therefore evaluate the ethics of human cloning, in particular the potential role of nurses.

This article reviews the ethical considerations of reproductive human cloning, discusses the main reasons for concern, and reflects a nursing perspective regarding this issue.
Exploratory Practice: rethinking practitioner research in language teaching
Authors: Allwright Dick
Published: May 2003

This paper is an introduction to the rest of this Special Issue of Language Teaching Research devoted entirely to Exploratory Practice (EP), a form of practitioner research. It is also an introduction to EP itself, telling the story of the development of its practices and its principles over the last ten or so years. Readers already familiar with EP may wish to go directly to the other seven papers in this issue, for illustrations of EP in practice, for research about EP, and for a more thorough review of the relevant research literature (see especially the papers by Miller and by Perpignan).

The case for EP presented below is based on a perceived need for practitioner research to be rethought: to be refocused on understanding, and ultimately on a concern for the quality of life in the language classroom, for both teachers and learners. The paper includes, in Section VII, a brief introduction to the other papers in this volume.
Decisions and decision making in the Istanbul Exploratory Practice experience
Authors: Bartu Hülya
Published: May 2003

This paper makes its distinctive contribution to this collection by taking us behind the puzzlement processes of Exploratory Practice (EP) to help us understand the interactive workings of an EP group, and in particular the threats to sustainability that emerged. It reports a discourse analytic enquiry into the nature of the decisions taken and the decision-making process employed at the EP group meetings held at the Teachers’ Centre of the British Council in Istanbul between the years 1994 and 1997. The EP group consisted of three regularly attending core members, who held meetings with a total of 11 teachers and teacher trainers from various institutions in Istanbul. In addition to the extensive supplementary data collected over the time span, the selected basic data consist of 13 hours of audio-recording of six group meetings. Initial examination of the data revealed that decisions were taken in identifiable long stretches of discourse, beginning with an initiation, continuing with negotiation, which can further be categorized into clarification, contribution, acceptance, and rejection moves, and ending with finalization. The analysis based on this model suggested that the group made three types of decisions: content, (i.e., what do we work on?), procedure (i.e., how do we work?) and aims (i.e., why do we work?). The most general conclusion that can be drawn from the study is that the group could not complete the EP stages due to recurrences of past decisions, different attitudes and expectations of members, and lack of a systematic reflection and evaluation component in their mode of work. The article ends with implications and suggestions for EP groups in similar contexts in the future.
Researching teacher-consultancy via Exploratory Practice
Authors: Miller Inés K.
Published: May 2003

This paper provides much of the theoretical background to Exploratory Practice (EP) that it was not possible to cover in the introductory paper to this collection. It also illustrates how the framework of EP can be invoked in the context of doctoral research. I report and comment on my reflexive doctoral study, which focuses on my own professional development as an EP teacher-consultant (Miller, 2001). I added an academic investigative dimension to my already reflexive practitioner research with a view to creating opportunities for working towards enriched understandings of the unfolding of two longitudinal teacher-consultancy encounters in which I worked, within EP (Allwright, 1992-2002), individually, as an EFL consultant to/with two practising EFL teachers.

I claim that my paradoxically reflexive positioning in both my practitioner and academic research practices combined to enhance my understandings of the ‘unrepresentable’ management of reflection in the sessions. I captured the interactional delicacy of the evolving teacher-consultant relationship through longitudinal topic-footing frame micro-analyses.
Invited commentary on Learning disabilities and ethnicity
Authors: Biswas Asit
Published: May 2003

In her article, O'Hara (2003, this issue) has concisely addressed the multitude of complex issues relating to ethnicity in people with learning disabilities, to their carers and to provision for services. The article brings out the interplay between culture, race, ethnicity and learning disability, using an interactional model.
Death and dying in literature
Authors: Skelton John
Published: May 2003

This paper considers how death and dying are presented in literature. A wide range of texts, principally but not exclusively from the English language tradition, is used to illustrate themes. Broad categories are suggested for the study of death: some authors give personal accounts of their impending death or their sense of bereavement; some use literature to structure and order our thoughts about death; and some treat death as a literary device, using it, for example, as a symbolic representation of the decay of society. It concludes that the biggest obstacles that health professionals and patients face as they attempt to understand death in literature are concerned not with a lack of appropriate emotional depth, but with difficulties either in understanding the conventions of literature or in coming to terms with the cultural gaps imposed by time and place.
Invited commentary on Death and dying in literature
Authors: Sims Andrew
Published: May 2003

Why? … because. This commentary to John Skelton's paper (Skelton, 2003, this issue) addresses the question, ‘Why should I, a busy consultant serving a population of 40 000 in north Lincolnshire and having considerable difficulty in keeping up with the latest developments about antipsychotic drugs, use my precious time for CPD reading about death and dying in literature?’ The answer is two-fold: death and dying is intrinsically an important and relevant subject for psychiatrists; and literature gives useful opportunities for modelling, comparing, contrasting and experimenting with circumstances removed from the patient's immediate situation but still recognised as ‘real life’. Great literature demonstrates authenticity. If the experiences described are true to life, perhaps the strategies that were used in this literary work, or are suggested through their absence, may be effective in your patient's (or even your own) predicament. Literature, or ‘the humanities', can enhance good practice in medicine (Evans & Greaves, 1999).
IGDA. 8: Idiographic (personalised) diagnostic formulation
Authors:   IGDA Workgroup, WPA
Published: May 2003

The diagnostic process involves more than simply identifying a disorder or distinguishing one disorder from another. It should lead to a thorough, contextualised and interactive understanding of a clinical condition and of the wholeness of the person who presents for evaluation and care.
Mental health of Kosovan Albanian refugees in the UK
Authors: Turner Stuart W. , Bowie Cameron , Dunn Graham , Shapo Laidon , Yule William
Published: May 2003

Background

In 1999 the UK received 4346 refugees from Kosovo.

Aims

To determine the prevalence of mental health problems in this group.

Method

A sample of 842 adults was surveyed. All were asked to complete self-report questionnaires (translated into Kosovan Albanian). A subset of 120 participants were later interviewed in Albanian using the Clinician Administered PTSD (post-traumatic stress disorder) Scale and a depression interview.

Results

The study yielded estimates of prevalence of PTSD and depression. Self-report measures appear to overestimate the prevalence of these disorders. Just under half of the group surveyed had a diagnosis of PTSD and less than one-fifth had a major depressive disorder.

Conclusions

These results may be taken as a sign of the resilience of many who survived this conflict but they also imply that there is still a substantial need for good health and social care in a significant proportion. Psychosocial interventions are likely to be an important part of the treatment programme.
Psychotherapy training experience in an inner-city psychiatry rotation
Authors: Podlejska-Eyres Maria , Stern Julian
Published: May 2003

Aims and Method

A postal questionnaire was circulated to all psychiatrists who had completed their basic specialist training on the Royal London Hospital training scheme within the last 7.5 years. The aim of the questionnaire was to explore their psychotherapy experience while on the rotation.

Results

The response rate was 95%. The respondents had a broad experience of both didactic and case work that they valued highly. Over half of them wished for an even greater exposure to psychotherapy during their basic training.

Clinical Implications

The results of our survey suggest that with the dedication of both the trainees and trainers, it is possible to have a comprehensive psychotherapy experience while working on a busy inner-city rotation.
Service innovations
Authors: Chowdhury U. , Caulfield C. , Heyman I.
Published: May 2003

Aims and Method

Young people attending the Maudsley obsessive–compulsive disorder (OCD) children's clinic had expressed an interest in meeting other similar young people with OCD. A group was set up comprising 6-weekly sessions focusing on psycho-education and support.

Results

Seven young people (mean age: 14 years 4 months; age range: 11 years 11 months to 16 years 6 months) took part. Feedback questionnaires showed that all the participants found the group helpful and enjoy-able. They felt less isolated and more confident about dealing with OCD.

Clinical Implications

Establishment of groups may be a valuable way of increasing awareness and knowledge on aspects of OCD, as well as providing much-needed psycho-social support to patients.
Psychiatric practice in Iran and the UK
Authors: Abad Nazir Hashemi Mohammad , London Mervyn
Published: May 2003

More than any other area of medicine, psychiatry is influenced greatly by the cultural setting in which it is practised. Iran and the UK have similar-sized populations, but are very different in many other respects. The opportunity arose to compare psychiatric practice in these two countries when one of us (N.H.) spent 3 months visiting mental health services at a UK centre.
Pre-registration house officer training in psychiatry: the London experience
Authors: Herzberg Joe , Aitken Maryanne , Moss Fiona
Published: May 2003

Aims and Method

To evaluate whether new pre-registration house officer posts in psychiatry deliver training leading to increased confidence in target skills, based on General Medical Council requirements, and to evaluate trainees' satisfaction with these posts. A structured questionnaire was filled out by the first nine incumbents of the PRHO posts before and after the placements.

Results

Trainees' confidence improved in all the target skills and the posts were all rated as good or excellent. The posts attracted trainees who were potentially interested in a career in psychiatry or general practice.

Clinical Implications

PRHO posts in psychiatry deliver training that meets General Medical Council objectives, and trainees' confidence with core psychiatric skills improves after undertaking the placements.