bluuebunny/crossref_metadata_2025 huggingface dataset:
Aortic Stiffness Is an Independent Predictor of Fatal Stroke in Essential Hypertension
Authors: Laurent Stéphane , Katsahian Sandrine , Fassot Céline , Tropeano Anne-Isabelle , Gautier Isabelle , Laloux Brigitte , Boutouyrie Pierre
Published: May 2003

Background and Purpose—

Pulse pressure is a stronger predictor of cardiovascular events than systolic or diastolic blood pressure in large cohorts of French and North American patients. However, its influence on stroke is controversial. Large-artery stiffness is the main determinant of pulse pressure. The influence of arterial stiffness on the occurrence of stroke has never been demonstrated. Our aim was to establish the relationship between aortic stiffness and stroke death in hypertensive patients.

Methods—

We included, in a longitudinal study, 1715 essential hypertensive patients who had a measurement of arterial stiffness at entry (ie, between 1980 and 2001) and no overt cardiovascular disease or symptoms. Mean follow-up was 7.9 years. At entry, aortic stiffness was assessed from the carotid-femoral pulse wave velocity. A Cox proportional hazard regression model was used to estimate the relative risk (RR) of stroke and coronary deaths.

Results—

Mean±SD age at entry was 51±13 years. Twenty-five fatal strokes and 35 fatal coronary events occurred. Pulse wave velocity significantly predicted the occurrence of stroke death in the whole population. There was a RR increase of 1.72 (95% CI, 1.48 to 1.96;
P
<0.0001) for each SD increase in pulse wave velocity (4 m/s). The predictive value of pulse wave velocity remained significant (RR=1.39 [95% CI, 1.08 to 1.72];
P
=0.02) after full adjustment for classic cardiovascular risk factors, including age, cholesterol, diabetes, smoking, mean blood pressure, and pulse pressure. In this population, pulse pressure significantly predicted stroke in univariate analysis, with a RR increase of 1.33 (95% CI, 1.16 to 1.51) for each 10 mm Hg of pulse pressure (
P
<0.0001) but not after adjustment for age (RR=1.19 [95% CI, 0.96 to 1.47];
P
=0.10).

Conclusions—

This study provides the first evidence, in a longitudinal study, that aortic stiffness is an independent predictor of fatal stroke in patients with essential hypertension.
Is Thrombogenesis in Atrial Fibrillation Related to Matrix Metalloproteinase-1 and Its Inhibitor, TIMP-1?
Authors: Marín Francisco , Roldán Vanessa , Climent Vicente , García Amaya , Marco Pascual , Lip Gregory Y.H.
Published: May 2003

Background and Purpose—

Decreased matrix metalloproteinase-1 (MMP-1) and increased levels of its inhibitor, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), reflect impaired matrix degradation with an increase in fibrosis. A prothrombotic state has been described in atrial fibrillation (AF), increasing the risk of stroke and thromboembolism. Because structural abnormalities and remodeling of atria have been observed in AF, we hypothesized that the prothrombotic state in AF may be related to abnormal indexes of matrix degradation.

Methods—

We studied 48 consecutive patients (30 men; age, 70.5±9.0 years) with chronic nonrheumatic AF who were not on anticoagulation. Plasma levels of MMP-1, TIMP-1, and prothrombin fragment 1+2 (F1+2, an index of thrombogenesis) were measured by enzyme-linked immunosorbent assay. M-mode, 2-dimensional, and Doppler echocardiographic studies were performed in all patients. Research indexes were compared with data from 32 control subjects in sinus rhythm who were of similar age and sex.

Results—

Patients with AF had lower levels of MMP-1 (
P
=0.011) but increased levels of TIMP-1 (
P
=0.033) and F1+2 (
P
<0.001) and a higher ratio of TIMP-1 to MMP-1 (
P
=0.009) compared with control subjects. After adjustment for sex, age, hypertension, and diabetes, TIMP-1 levels and the ratio of TIMP-1 to MMP-1 correlated with F1+2 levels (
r
=0.24,
P
=0.038; and
r
=0.26,
P
=0.023, respectively). In multivariate analysis, there was no independent relationship between MMP-1, TIMP-1, or ratio of TIMP-1 to MMP-1 and the presence of AF.

Conclusions—

Patients with AF have evidence of impaired matrix degradation, but this was not independently associated with the presence of AF on multivariate analysis. However, an independent relationship was found between the MMP/TIMP system and prothrombotic state (assessed by F1+2 levels).
Bone Mineral Density and Stroke
Authors: Mussolino Michael E. , Madans Jennifer H. , Gillum R.F.
Published: May 2003

Background and Purpose—

We sought to assess the long-term predictive usefulness of bone mineral density (BMD) for stroke incidence and stroke mortality.

Methods—

The First National Health and Nutrition Examination Survey data were obtained from a nationally representative sample of noninstitutionalized civilians. A cohort of 3402 white and black subjects 45 through 74 years of age at baseline (1971 to 1975) was observed through 1992. Hospital records and death certificates were used to identify a total of 416 new stroke cases.

Results—

Results were evaluated to determine the relative risk (RR) for stroke per 1-SD decrease in BMD, after controlling for age at baseline, smoking status, alcohol consumption, history of diabetes, history of heart disease, education, body mass index, recreational physical activity, and blood pressure medication. In Cox proportional-hazards analyses, incidence of stroke was not associated with a decrease in BMD in any of the 3 race-sex groups: white men (RR, 1.01; 95% CI, 0.86 to 1.19;
P
=0.88), white women (RR, 1.13; 95% CI, 0.93 to 1.38;
P
=0.21), or blacks (RR, 0.93; 95% CI, 0.72 to 1.21;
P
=0.60). No association between BMD and stroke mortality was found (RR, 1.03; 95% CI, 0.86 to 1.23;
P
=0.77).

Conclusions—

In a large national study, no significant associations of BMD and stroke incidence or mortality were found for whites or blacks.
Changes in Linear Dynamics of Cerebrovascular System After Severe Traumatic Brain Injury
Authors: Müller M. , Bianchi O. , Erülkü S. , Stock C. , Schwerdtfeger K.
Published: May 2003

Background and Purpose—

We sought to describe the dynamic changes in the cerebrovascular system after traumatic brain injury by transfer function estimation and coherence.

Methods—

In 42 healthy volunteers (mean±SD age, 37±17 years; range, 17 to 65 years), spontaneous fluctuations of middle cerebral artery blood flow velocity and of finger blood pressure (BP) were simultaneously recorded over a period of 10 minutes under normocapnic and hypocapnic conditions to generate normative spectra of coherence, phase shift, and gain over the frequency range of 0 to 0.25 Hz. Similar recordings were performed in 24 patients with severe traumatic brain injury (Glasgow Coma Scale score ≤8; mean±SD age, 50±20 years) serially on days 1, 3, 5, and 8 after trauma. Cranial perfusion pressure was kept at >70 mm Hg. Each blood flow velocity/BP recording was related to the presence or absence of middle cerebral artery territory brain parenchyma lesions on cranial CT performed within a close time frame.

Results—

In controls, hypocapnia decreased coherence (0.0 to 0.20 Hz), increased phase shift (0.0 to 0.17 Hz), and decreased gain in the frequency range of 0.0 to 0.11 Hz but increased gain at frequencies of 0.20 to 0.25 Hz (
P
<0.01 for all frequency ranges reported). In patients with traumatic brain injury, 102 investigations were possible. Compared with controls, coherence was increased in the frequency range <0.03 Hz and between 0.13 and 0.25 Hz in both normocapnia and hypocapnia, irrespective of the CT findings. Gain was unchanged in normocapnia and in the absence of a CT lesion. Gain was decreased in hypocapnia at frequencies >0.12 Hz irrespective of the presence/absence of a CT lesion. Phase shift decreased rapidly between 0.06 and 0.13 Hz under hypocapnic conditions and under normocapnic conditions in the presence of a CT lesion (
P
< 0.01).

Conclusions—

Use of spontaneous fluctuations of blood flow velocity and BP to assess the cerebrovascular system dynamically requires consideration of the Pa
co
2
level. In different conditions, including severe traumatic brain injury, the cerebrovascular system behaves linearly only in parts of the investigated frequency range.
Sex Differences in the Clinical Presentation, Resource Use, and 3-Month Outcome of Acute Stroke in Europe
Authors: Di Carlo Antonio , Lamassa Maria , Baldereschi Marzia , Pracucci Giovanni , Basile Anna Maria , Wolfe Charles D.A. , Giroud Maurice , Rudd Anthony , Ghetti Augusto , Inzitari Domenico
Published: May 2003

Background and Purpose—

The information on the existence of sex differences in management of stroke patients is scarce. We evaluated whether sex differences may influence clinical presentation, resource use, and outcome of stroke in a European multicenter study.

Methods—

In a European Concerted Action involving 7 countries, 4499 patients hospitalized for first-in-a-lifetime stroke were evaluated for demographics, risk factors, clinical presentation, resource use, and 3-month survival, disability (Barthel Index), and handicap (Rankin Scale).

Results—

Overall, 2239 patients were males and 2260 females. Compared with males, female patients were significantly older (mean age 74.5±12.5 versus 69.2±12.1 years), more frequently institutionalized before stroke, and with a worse prestroke Rankin score (all values
P
<0.001). History of hypertension (
P
=0.007) and atrial fibrillation (
P
<0.001) were significantly more frequent in female stroke patients, as were coma (
P
<0.001), paralysis (
P
<0.001), aphasia (
P
=0.001), swallowing problems (
P
=0.005), and urinary incontinence (
P
<0.001) in the acute phase. Brain imaging, Doppler examination, echocardiogram, and angiography were significantly less frequently performed in female than male patients (all values
P
<0.001). The frequency of carotid surgery was also significantly lower in female patients (
P
<0.001). At the 3-month follow-up, after controlling for all baseline and clinical variables, female sex was a significant predictor of disability (odds ratio [OR], 1.41; 95% CI 1.10 to 1.81) and handicap (OR, 1.46; 95% CI 1.14 to 1.86). No significant gender effect was observed on 3-month survival.

Conclusions—

Sex-specific differences existed in a large European study of hospital admissions for acute stroke. Both medical and sociodemographic factors may significantly influence stroke outcome. Knowledge of these determinants may positively impact quality of care.
The New York Islands AVM Study
Authors: Stapf C. , Mast H. , Sciacca R.R. , Berenstein A. , Nelson P.K. , Gobin Y.P. , Pile-Spellman J. , Mohr J.P.
Published: May 2003

Background and Purpose—

Prospective population-based data on the incidence of brain arteriovenous malformation (AVM) hemorrhage are scarce. We studied lifetime detection rates of brain AVM and incident AVM hemorrhage in a defined population.

Methods—

The New York islands (ie, Manhattan Island, Staten Island, and Long Island) comprise a 9 429 541 population according to the 2000 census. Since March 15, 2000, all major New York islands hospitals have prospectively reported data on consecutive patients living in the study area with a diagnosis of brain AVM and whether the patient had suffered AVM hemorrhage. Patients living outside the ZIP code–defined study area were excluded from the study population.

Results—

As of June 14, 2002, 284 prospective AVM patients (mean±SD age, 35±18 years; 49% women) were encountered during 21 216 467 person-years of observation, leading to an average annual AVM detection rate of 1.34 per 100 000 person-years (95% CI, 1.18 to 1.49). The incidence of first-ever AVM hemorrhage (n=108; mean age, 31±19 years; 45% women) was 0.51 per 100 000 person-years (95% CI, 0.41 to 0.61). The estimated prevalence of AVM hemorrhage among detected cases (n=144; mean age, 33±19 years; 50% women) was 0.68 per 100 000 (95% CI, 0.57 to 0.79).

Conclusions—

Our prospective data, spanning 27 months, suggest stable rates for AVM detection and incident AVM hemorrhage. Approximately half of AVM patients may suffer intracranial hemorrhage.
Scottish Intracranial Vascular Malformation Study (SIVMS)
Authors: Al-Shahi Rustam , Bhattacharya Jo J. , Currie David G. , Papanastassiou Vakis , Ritchie Vaughn , Roberts Richard C. , Sellar Robin J. , Warlow Charles P.
Published: May 2003

Background and Purpose—

The rarity of intracranial vascular malformations (IVMs) and the infrequency of their outcomes make large, prolonged cohort studies the best means to evaluate their frequency and prognosis.

Methods—

The Scottish Intracranial Vascular Malformation Study (SIVMS) is a prototype prospective, population-based study of adults resident in Scotland and diagnosed for the first time with an IVM after January 1, 1999. We evaluated the design of SIVMS using 2 complete years of data for adults with arteriovenous malformations (AVMs) of the brain.

Results—

A collaborative network of clinicians, radiologists, and pathologists, combined with coding of hospital discharge data and death certificates, recruited a cohort distributed in proportion to the Scottish population. Coding (with
International Classification of Diseases, 10th Revision
[
ICD-10
] codes Q28.2 and I60.8) had a sensitivity of 72% (95% CI, 61% to 80%) and a positive predictive value of 46% (95% CI, 38% to 55%) for detecting incident brain AVMs. Adults who were detected by coding alone were significantly (
P
<0.05) younger, more likely to present with hemorrhage, more frequently investigated with catheter angiography, and more likely to be treated. Adults recruited from tertiary referral centers were significantly more likely to be investigated with catheter angiography and to be treated. Using catheter angiography as a diagnostic requirement for brain AVMs significantly biases the cohort toward younger adults presenting with hemorrhage and receiving treatment.

Conclusions—

Population-based studies of IVM frequency and prognosis should use multiple overlapping sources of case ascertainment, and such studies of brain AVMs should not require catheter angiography to be the diagnostic standard.
Homocysteine and Risk of Recurrent Stroke
Authors: Boysen Gudrun , Brander Thomas , Christensen Hanne , Gideon Rolf , Truelsen Thomas
Published: May 2003

Background and Purpose—

The goals of this work were to investigate whether elevated total homocysteine (tHcy) measured within 24 hours of acute stroke was an independent risk factor for recurrent stroke and to compare levels of tHcy in groups of patients with diagnoses of ischemic and hemorrhagic cerebrovascular events.

Methods—

We performed a longitudinal study of 1039 stroke patients (mean age, 75 years). Fasting tHcy was measured the morning after primary admission. Patients were followed up for 15 months.

Results—

Serum homocysteine was significantly higher in the 105 patients who experienced a recurrent stroke during the follow-up period than in patients without recurrence. The geometric mean±SD was 13.4±10.7 versus 11.8±7.1 μmol/L (
P
=0.008), and the mean difference was 1.2 μmol/L [95% confidence interval (CI), 1.05 to 2.3]. In a multiple logistic regression model, tHcy was an independent explanatory variable of recurrent stroke within 15 months (odds ratio, 1.3; 95% CI, 1.1 to 1.5) for each increase in tHcy of 10 μmol/L. At the index event, serum homocysteine was significantly higher in 909 patients with ischemic cerebrovascular events than in 130 patients with intracerebral hemorrhage (geometric mean, 12.1±7.3 versus 10.4±5.2 μmol/L;
P
<0.001).

Conclusions—

The data in this study indicate that elevated tHcy is an independent risk factor for recurrent stroke.
Lipoprotein Lipase (
LPL
) Gene Variation and Progression of Carotid Artery Plaque
Authors: Spence J. David , Ban Matthew R. , Hegele Robert A.
Published: May 2003

Background and Purpose—

Coding single nucleotide polymorphisms (cSNPs) in the lipoprotein lipase (
LPL
) gene have been associated with lipoprotein phenotypes and vascular disease risk. We studied the association between
LPL
cSNPs and a novel noninvasive measure of disease, namely, cross-sectional carotid plaque area (CPA) on B-mode ultrasound.

Methods—

Four hundred fifty-two patients from an atherosclerosis prevention clinic had determinations of baseline and total CPA. Traditional atherosclerosis risk factors were recorded, and the
LPL
D9N, N291S, and S447X cSNPs were genotyped. Multiple regression analysis was used to identify determinants of CPA.

Results—

Minor allele frequencies for
LPL
D9N, N291S, and S447X were 2.8%, 0.9%, and 4.4%, respectively. There were no significant between-genotype differences in treated fasting lipids. The
LPL
D9N genotype was a significant predictor of both baseline CPA (
P
=0.008) and plaque progression from baseline to 1 year later (
P
=0.001). Heterozygotes for the N9 allele had higher mean baseline CPA and plaque progression than did
LPL
D9/D9 homozygotes.

Conclusions—

LPL
D9N genotype may be a determinant of atherosclerosis as estimated by static baseline CPA and by progression of CPA.
Hypodensity of >1/3 Middle Cerebral Artery Territory Versus Alberta Stroke Programme Early CT Score (ASPECTS)
Authors: Mak Henry K.F. , Yau Kelvin K.W. , Khong Pek-Lan , Ching Alex S.C. , Cheng Pui-Wai , Au-Yeung Paul K.M. , Pang Peter K.M. , Wong Kenny C.W. , Chan Bernard P.L.
Published: May 2003

Background—

The one third middle cerebral artery territory (⅓ MCA) method and the Alberta Stroke Program Early CT Score (ASPECTS) were used to detect significant early ischemic changes (EIC) on CT brain of acute stroke patients. We sought to compare the reliability of the 2 methods in routine clinical practice.

Methods—

Eighty consecutive patients admitted to a community hospital in Hong Kong with suspected acute ischemic stroke and a CT brain scan performed within 6 hours of symptom onset were included. Five blinded observers (1 neurologist, 2 general radiologists, and 2 neuroradiologists) independently evaluated the scans, using the ATLANTIS/CT Summit criteria for >⅓ MCA involvement, and ASPECTS ≤7. Kappa statistics were used to determine interobserver agreement.

Results—

Significant EIC were present in 11.4% of the scans with the ⅓ MCA method, and 19.4% with ASPECTS. For >⅓ MCA involvement, all observers agreed in 57 cases (71%), with moderate interobserver agreement (κ=0.49). For ASPECTS ≤7, all observers agreed in 34 cases (42%), with fair interobserver agreement (κ=0.34). After prevalence and bias adjustments, substantial (prevalence-adjusted bias-adjusted κ [PABAK]=0.74) and moderate (PABAK=0.44) agreements were found for the ⅓ MCA method and ASPECTS respectively.

Conclusions—

The ⅓ MCA method was more reliable in detecting significant EIC on CT brain within 6 hours of stroke onset in routine clinical practice, whereas ASPECTS was able to detect significant EIC in a higher proportion of these early scans.
ACHEROUSIA UND ELYSION: ANMERKUNGEN IM HINBLICK AUF DEREN VERWENDUNG AUCH IM CHRISTLICHEN KONTEXT
Authors:   Kraus
Published: May 2003

Mentioned on a parchment double-leaf kept in Vienna (P.Vindob.G 39756) presenting a fragmentary codex of the so-called Apocalypse of Peter, 'Aχερoυσια λιμνη and 'Hλυσιoν πεδιoν may surprise the reader. How to explain that such classical terms were used in a Christian text? By establishing a general basis of data for the usage and meaning of both elements in (late) antiquity, the aim of this paper is to shed light on the underlying motives and ideas behind the adoption of the Acherousian lake and the Elysion by early Christian authors and scribes, a fact which has rarely received full attention.
AMICI ET SODALES: AN EXAMINATION OF A DOUBLE MOTIF IN PLAUTUS
Authors: Maurice Lisa
Published: May 2003

One of the ways in which Plautus investigates friendship is through his use of the stock characters so central to Roman comedy. Among the twelve stock characters of comedy that Apuleius lists, appears the figure of the sodalis opitulator (the 'helpful mate'), who has not so far drawn much attention. Not only does Plautus use this character frequently, in five of his twenty extant plays he employs not one friend, but two, as a double motif. In these plays, Plautus uses these double stock characters to parody the ideals of friendship which had developed in the literary tradition, and to play with the conventions of drama as part of a metatheatrical approach to comedy. By a doubling of this motif, Plautus highlights friendship, in order to look at other literary or dramatic themes that include the ideal literary friendship, the supremacy of the Plautine slave and drama itself.
LEGAL LANGUAGE IN PLAUTUS WITH SPECIAL REFERENCE TO TRINUMMUS
Authors:   Karakasis
Published: May 2003

The present article deals with the way in which Plautus uses the legal language and practice of his own day in his comedy, Trinummus, for his literary purposes as a comic dramatist. The paper investigates in the first place some brief references to divorce, the hereditas sine sacris and loans given by slaves, and then examines three main legal problems of the comedy, i.e., mandatum, sponsio and dos. The article argues for the legal character of the mandatum between Charmides and Callicles, as well as for the lack of legal validity of Lesbonicus' and Lysiteles' transactions and examines the way such legal actions are used by Plautus for intensifying the comic outcome. It concludes that Plautus uses legal language as a means for character delineation, character motivation and plot development.
LAMENT IN EURIPIDES' TROJAN WOMEN
Authors: Suter Ann
Published: May 2003

This article summarizes the findings of an unpublished PhD dissertation, "The Form of Lament in Greek Tragedy" by E. Wright, which provide for the first time objective criteria for identification of lamentation in tragedy. It applies these criteria to the Trojan Women, and argues, on the basis of metrical and stylistic devices, that virtually every scene in the Trojan Women shows the characteristics of lament. The play is, from both the minute technical, and the overall structural, point of view, a lament. This provides explanations for some of the long-standing critical issues of the play, e.g., no unity, no plot, an ill-conceived prologue. The article then considers also how the Trojan Women fits into current discussions of lament as a gendered genre. It replies especially to work on the development of 5th-century Athenian attitudes towards female lament, in which a pattern of increased criticism and restriction, it is argued, is reflected in the changing treatment of lament in Athenian tragedy. The treatment of lament in the Trojan Women does not conform to this perceived development. This suggests that there were still a variety of attitudes current and influential in late 5th-century Athens towards female lamentation.
TREMULOQUE GRADU VENIT AEGRA SENECTUS: OLD AGE IN OVID'S METAMORPHOSES
Authors:   Nikolopoulos
Published: May 2003

Although aging is not a metamorphosis stricto sensu, it is a process that affects the shape of the body. This paper explores the ambivalent representation of old age and its interplay with the ostensible theme of Ovid's encyclopedic poem on bodies changing shapes. Aging in the Metamorphoses is mainly a physiological process, which affects men and women alike, but may be reversed by means of magic. It is also one of the trappings of divinity: gods and goddesses often disguise themselves as old women, in order to deceive or advise humans. Even the poem's narrator, 'Ovid', frequently assumes the persona of the elderly in an act of self-transformation.
THE HOMERIC SCHOLIA ON FOCALIZATION
Authors: Nünlist René
Published: May 2003

Questions related to the point of view within a narrative text are nowadays discussed under the narratological rubric of focalization. An examination of pertinent Homeric scholia shows that ancient literary critics regularly treated questions of focalization, although they neither had a specific term for the concept nor discussed it in its own right. Their interpretations not only deal with the differences in focalization between the narrator-text and the speeches but also include what is now called 'embedded focalization', i.e. the representation of a character's point of view in the narrator-text. The relevant scholia are presented both in Greek and in English translation.
JENSEITS VON RAUM, ZEIT UND GEMEINSCHAFT „CHRIST-SEIN" NACH DEM THOMASEVANGELIUM
Authors: Rau Eckhard
Published: May 2003

Die „kleinen Einheiten" des EvThom sind im Kontakt zur Jesusüberlieferung der werdenden Großkirche geformt. In polemischer Abgrenzung von deren christologischen, heilsgeschichtlichen und eschatologischen Überzeugungen begegnet uns hier ein Raum und Zeit enthobener Jesus, der sich denen anverwandelt, die in radikaler Vereinzelung den von ihm gewiesenen Weg ins Königreich einschlagen. Wer dies tut, kehrt zurück in den nondualen, allen Zweiheiten vorausliegenden Ursprung allen Seins und gewinnt dadurch einen Status, dessen Konformität mit Jesus eine überraschende Perspektive für die Frage nach der Ausbildung des spezifischen Profils der Jesusüberlieferung des EvThom eröffnet.
Hemostasis and coagulation at a hematocrit level of 0.85: functional consequences of erythrocytosis
Authors: Shibata Junpei , Hasegawa Jo , Siemens Hans-Joachim , Wolber Eva , Dibbelt Leif , Li Dechun , Katschinski Dörthe M. , Fandrey Joachim , Jelkmann Wolfgang , Gassmann Max , Wenger Roland H. , Wagner Klaus F.
Published: May 2003

We have generated a transgenic mouse line that reaches a hematocrit concentration of 0.85 due to constitutive overexpression of human erythropoietin in an oxygen-independent manner. Unexpectedly, this excessive erythrocytosis did not lead to thrombembolic complications in all investigated organs at any age. Thus, we investigated the mechanisms preventing thrombembolism in this mouse model. Blood analysis revealed an age-dependent elevation of reticulocyte numbers and a marked thrombocytopenia that matched the reduced megakaryocyte numbers in the bone marrow. However, platelet counts were not different from wild-type controls, when calculations were based on the distribution (eg, plasma) volume, thereby explaining why thrombopoietin levels did not increase in transgenic mice. Nevertheless, bleeding time was significantly increased in transgenic animals. A longitudinal investigation using computerized thromboelastography revealed that thrombus formation was reduced with increasing age from 1 to 8 months in transgenic animals. We observed that increasing erythrocyte concentrations inhibited profoundly and reversibly thrombus formation and prolonged the time of clot development, most likely due to mechanical interference of red blood cells with clot-forming platelets. Transgenic animals showed increased nitric oxide levels in the blood that could inhibit vasoconstriction and platelet activation. Finally, we observed that plasmatic coagulation activity in transgenic animals was significantly decreased. Taken together, our findings suggest that prevention of thrombembolic disease in these erythrocytotic transgenic mice was due to functional consequences inherent to increased erythrocyte concentrations and a reduction of plasmatic coagulation activity, the cause of which remains to be elucidated.
Elderly humans exposed to concentrated air pollution particles have decreased heart rate variability
Authors: Devlin R.B. , Ghio A.J. , Kehrl H. , Sanders G. , Cascio W.
Published: May 2003

Air pollution particles are thought to kill >500,000 people worldwide each year. The population most at risk appears to be elderly people with respiratory and cardiovascular disease. As yet, no commonly accepted mechanism has been proposed which can explain the cause of these deaths.

Heart rate variability (HRV) was assessed in healthy elderly adults between the ages of 60 and 80 who were exposed twice for 2 h: once to clean air and once to concentrated ambient air pollution particles (CAPS). Changes in HRV were measured immediately before, immediately following, and 24 h after exposure.

Elderly subjects experienced significant decreases in HRV in both time and frequency domains immediately following exposure. Some of these changes persisted for at least 24 h. These data were compared with HRV data collected from young healthy volunteers exposed to CAPS in a previous study, in which no CAPS-induced changes in HRV were found.

These concentrated ambient air pollution particle-induced changes in heart rate variability in a controlled human exposure study extend similar findings reported in recent panel studies and suggest potential mechanisms by which particulate matter may induce adverse cardiovascular events.
Air pollution and the elderly: oxidant/antioxidant issues worth consideration
Authors: Kelly F.J. , Dunster C. , Mudway I.
Published: May 2003

The elderly are frequently classified as being particularly susceptible to air pollution. The basis of this increased sensitivity is not known but it is likely that it is linked to age-related impaired function of the lung. However, given this uncertainty and increased impact of air pollution of this section of the community there is a need to explore the mechanisms involved.

Gaseous air pollutants such as ozone and nitrogen dioxide, or many of the components adsorbed onto the surface of respirable particles, are either powerful oxidants or capable of generating free radicals. If unabated, oxidants can cause injury to the delicate cells that line the respiratory tract. Small molecular weight antioxidant defences present in respiratory tract lining fluid (RTLF) represent the first line of defence against a range of oxidants that enter the lung. The quantity and quality of the RTLF airways antioxidant network are, therefore, likely to be important determinants of the impact of the oxidant challenge on the underlying respiratory epithelium.

As yet, comprehensive information on the distribution and variability of respiratory tract lining fluid antioxidant defences is only available in young, mainly healthy volunteers. Studies undertaken in patients with a range of respiratory diseases suggest that marked changes in the distribution of respiratory tract lining fluid antioxidants can occur. Information is not currently available on the impact of ageing on the respiratory tract lining fluid antioxidant defence network. As several respiratory tract lining fluid antioxidants are of dietary origin, the elderly, who often have different dietary patterns to younger individuals, may have decreased availability of important antioxidants. Given these possibilities, a better understanding of respiratory tract lining fluid antioxidant defences in the aged lung is warranted.
Mechanism of lung injury caused by PM10and ultrafine particles with special reference to COPD
Authors: MacNee W. , Donaldson K.
Published: May 2003

Particulate air pollution (particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10)) has strong associations with the adverse health events detected by epidemiological studies in chronic obstructive pulmonary disease patients in diverse geographical locations. Transition metals may determine the toxic effects of PM10through oxidative stress which may be injurious as shown by an increase in airspace epithelial permeability and may lead to inflammation through the activation of transcription factors for pro‐inflammatory genes in both macrophages and epithelial cells. Recently, the present authors have shown that particulate air pollution may cause further molecular events that enhance transcription factor activation by causing acetylation of histones leading to unwinding of deoxyribonucleic acid (DNA) enhancing transcription factor DNA binding and increasing transcription for pro-inflammatory genes.

Further, ultrafine particles (<100 nm diameter), which have marked toxicity, may be responsible for some of the PM10adverse effects. The current authors have demonstrated that ultrafine carbon black (ufCB) does not have its effectsviatransition metal-mediated mechanisms. However, ufCB and other ultrafines generate free radicals at their surface as measured by a number of chemical assays and are able to cause oxidative stress to cells and this is likely to be a factor in their ability to cause inflammation. Changes in calcium resulting from oxidative stress within cells may be an additional factor leading to transcription of pro-inflammatory genes.

Understanding the mechanisms of the harmful effects of particulate air pollution in chronic obstructive pulmonary disease may help in risk strategy for individuals who are susceptible to the effects of air pollution.
Determinants of prognosis of COPD in the elderly: mucus hypersecretion, infections, cardiovascular comorbidity
Authors: Pistelli R. , Lange P. , Miller D.L.
Published: May 2003

In this paper, the authors update the present knowledge about three risk factors for the prognosis of chronic obstructive pulmonary disease (COPD), which may be particularly relevant in elderly people: mucus hypersecretion, respiratory infections, and cardiovascular comorbidity. Chronic mucus hypersecretion (CMH) is a common respiratory symptom in old age, the relevance of which is analysed on the basis of data collected during the first three rounds of the Copenhagen City Heart Study. In subjects aged ≥65 yrs, CMH was a strong predictor of the incidence of respiratory infections in a 10-yr follow-up period and it was also a strong predictor of death from COPD (relative risk=2.5). However, CMH was associated with consistently lower forced expiratory volume in one second (FEV1) values, but not with an accelerated decline of FEV1in this sample of an elderly population.

Acute respiratory infections (ARI) are extremely common at all ages, mostly mild self-limiting illnesses at a young age, but severe often fatal illnesses in elderly people already affected by a chronic disease such as COPD. This paper summarises the present knowledge about aetiology, pathology, prognostic relevance, and prevention of ARI. Furthermore, the areas in which further research is needed are listed. Clinical cohort studies clearly support the relevance of cardiovascular comorbidity for the short- and long-term prognosis of elderly subjects affected by severe COPD.

In this paper, the recently demonstrated association between particulate air pollution and cardiovascular events is reported to suggest the presence of an extremely susceptible cluster of elderly subjects in the population identified by the copresence of chronic obstructive pulmonary disease and cardiovascular comorbidity.
Poisoned patients as potential organ donors: postal survey of transplant centres and intensive care units
Authors: Wood David Michael , Dargan Paul Ivor , Jones Alison Linda
Published: May 2003

Background

The number of patients awaiting allograft transplantation in the UK exceeds the number of organs offered for transplantation each year. Most organ donors tend to be young, fit and healthy individuals who die because of trauma or sudden cardiac arrest. Patients who die from drug and poison intoxication tend to have similar characteristics but are less frequently offered as potential organ donors.

Methods

A postal questionnaire survey of all transplantation centres and an equal number of intensive care units in the UK was undertaken. The use of kidney, heart, lung, liver and pancreas transplants from poisoned patients following deliberate methanol ingestion, cardiac arrest presumed secondary to cocaine overdose, accidental domestic carbon monoxide inhalation and industrial cyanide exposure were used as case scenarios.

Results

Response rates were 70% for transplantation centres and 50% for intensive care unit directors. Over 80% of organs would be offered or discussed with transplant coordinators by intensive care unit directors. Transplantation physicians/surgeons would consider transplanting organs in up to 100% of case scenarios, depending on the organ and poisoning or intoxication involved.

Discussion

The postal survey presented here shows that most transplantation physicians and surgeons and intensive care unit directors would consider those who die following acute drug intoxication and poisoning as potential organ donors. The previously reported literature shows in general that transplanted organs from poisoned patients have good long-term survival, although the number of reports is small. Poisoned patients are another pool of organ donors who at present are probably underused by transplantation services.
Training in data definitions improves quality of intensive care data
Authors: Arts Daniëlle GT , Bosman Rob J , de Jonge Evert , Joore Johannes CA , de Keizer Nicolette F
Published: May 2003

Background

Our aim was to assess the contribution of training in data definitions and data extraction guidelines to improving quality of data for use in intensive care scoring systems such as the Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II in the Dutch National Intensive Care Evaluation (NICE) registry.

Methods

Before and after attending a central training programme, a training group of 31 intensive care physicians from Dutch hospitals who were newly participating in the NICE registry extracted data from three sample patient records. The 5-hour training programme provided participants with guidelines for data extraction and strict data definitions. A control group of 10 intensive care physicians, who were trained according the to train-the-trainer principle at least 6 months before the study, extracted the data twice, without specific training in between.

Results

In the training group the mean percentage of accurate data increased significantly after training for all NICE variables (+7%, 95% confidence interval 5%–10%), for APACHE II variables (+6%, 95% confidence interval 4%–9%) and for SAPS II variables (+4%, 95% confidence interval 1%–6%). The percentage data error due to nonadherence to data definitions decreased by 3.5% after training. Deviations from 'gold standard' SAPS II scores and predicted mortalities decreased significantly after training. Data accuracy in the control group did not change between the two data extractions and was equal to post-training data accuracy in the training group.

Conclusion

Training in data definitions and data extraction guidelines is an effective way to improve quality of intensive care scoring data.
Safety assessment of drotrecogin alfa (activated) in the treatment of adult patients with severe sepsis
Authors: Bernard Gordon R , Macias William L , Joyce David E , Williams Mark D , Bailey Joan , Vincent Jean-Louis
Published: May 2003

Introduction

Drotrecogin alfa (activated; recombinant activated protein C) was shown to reduce 28-day all-cause mortality in patients with severe sepsis and to have an acceptable safety profile in 1690 patients studied in the F1K-MC-EVAD (PROWESS) trial. We analyzed all available data on the safety of treatment with drotrecogin alfa (activated) in 2786 adult patients with severe sepsis enrolled in all phase 2 and 3 clinical trials, and in an estimated 3991 patients receiving the drug in commercial use.

Patients and method

Mortality and safety analyses were performed on all available data from adult severe sepsis patients enrolled in seven clinical trials as of 12 April 2002. Trial-specific safety data and spontaneously reported serious adverse events from commercial use were extracted from a pharmacovigilance database.

Results

The 28-day mortality rate for all adult patients who received active treatment in all clinical trials was 25.3% (704/2786). Serious bleeding events during the infusion period and 28-day study period occurred in 2.8% (79/2786) and 5.3% (148/2786) of patients, respectively. Of bleeding events during the infusion period, 43% (34/79) were procedure-related. Fatal serious bleeding events during the infusion period occurred in 0.4% (12/2786) of cases. Intracranial hemorrhage (ICH) events during the infusion period and 28-day study period occurred in 0.6% (16/2786) and 1.1% (32/2786) of patients, respectively. Ten out of the 16 ICH events occurring during the study drug infusion period were associated with severe thrombocytopenia (≤ 30,000/mm3) and/or meningitis. Serious bleeding and ICH events spontaneously reported from commercial use (n = 3991) occurred in 0.9% and 0.2% of patients, respectively.

Conclusion

Drotrecogin alfa (activated) significantly reduces mortality in severe sepsis. The efficacy and safety profiles of drotrecogin alfa (activated) have remained consistent over the conduct of multiple clinical trials. The most important serious adverse event associated with drotrecogin alfa (activated) treatment is bleeding. Additional clinical experience indicates that invasive procedures are associated with a substantial percentage of serious bleeding events, particularly those occurring at the start of infusion of the drug. Severe thrombocytopenia (for all serious bleeding events, including ICH) and meningitis (for ICH only) may be risk factors for serious bleeding. However, patients with severe thrombocytopenia and/or meningitis may be at greater risk for bleeding or ICH in the absence of drug therapy.
Genome-wide detection of segmental duplications and potential assembly errors in the human genome sequence
Authors: Cheung Joseph , Estivill Xavier , Khaja Razi , MacDonald Jeffrey R , Lau Ken , Tsui Lap-Chee , Scherer Stephen W
Published: May 2003

Background

Previous studies have suggested that recent segmental duplications, which are often involved in chromosome rearrangements underlying genomic disease, account for some 5% of the human genome. We have developed rapid computational heuristics based on BLAST analysis to detect segmental duplications, as well as regions containing potential sequence misassignments in the human genome assemblies.

Results

Our analysis of the June 2002 public human genome assembly revealed that 107.4 of 3,043.1 megabases (Mb) (3.53%) of sequence contained segmental duplications, each with size equal or more than 5 kb and 90% identity. We have also detected that 38.9 Mb (1.28%) of sequence within this assembly is likely to be involved in sequence misassignment errors. Furthermore, we have identified a significant subset (199,965 of 2,327,473 or 8.6%) of single-nucleotide polymorphisms (SNPs) in the public databases that are not true SNPs but are potential paralogous sequence variants.

Conclusion

Using two distinct computational approaches, we have identified most of the sequences in the human genome that have undergone recent segmental duplications. Near-identical segmental duplications present a major challenge to the completion of the human genome sequence. Potential sequence misassignments detected in this study would require additional efforts to resolve.
GoMiner: a resource for biological interpretation of genomic and proteomic data
Authors: Zeeberg Barry R , Feng Weimin , Wang Geoffrey , Wang May D , Fojo Anthony T , Sunshine Margot , Narasimhan Sudarshan , Kane David W , Reinhold William C , Lababidi Samir , Bussey Kimberly J , Riss Joseph , Barrett J Carl , Weinstein John N
Published: May 2003

We have developed GoMiner, a program package that organizes lists of 'interesting' genes (for example, under- and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. GoMiner provides quantitative and statistical output files and two useful visualizations. The first is a tree-like structure analogous to that in the AmiGO browser and the second is a compact, dynamically interactive 'directed acyclic graph'. Genes displayed in GoMiner are linked to major public bioinformatics resources.
ProSplicer: a database of putative alternative splicing information derived from protein, mRNA and expressed sequence tag sequence data
Authors: Huang Hsien-Da , Horng Jorng-Tzong , Lee Chau-Chin , Liu Baw-Jhiune
Published: May 2003

ProSplicer is a database of putative alternative splicing information derived from the alignment of proteins, mRNA sequences and expressed sequence tags (ESTs) against human genomic DNA sequences. Proteins, mRNA and ESTs provide valuable evidence that can reveal splice variants of genes. The alternative splicing information in the database can help users investigate the alternative splicing and tissue-specific expression of genes.
Hair analysis used to assess chronic exposure to the organophosphate diazinon: a model study with rabbits
Authors: Tutudaki Maria , Tsakalof Andreas K , Tsatsakis Aristidis M
Published: May 2003

The main purpose of the present study was to determine whether hair analysis would be a suitable method to assess chronic exposure of rabbits to the pesticide diazinon. A controlled study was designed, in which white rabbits of the New Zealand variety were systemically exposed to two dosage levels (15 mg/kg per day and 8 mg/kg per day) of the pesticide, through their drinking water, for a period of 4 months. Hair samples from the back of the rabbits were removed before commencing the experiment and at the end of the dosing period. Parallel experiments with spiked hair were carried out in order to design a simple and efficient method of extraction of diazinon from hair. The hair was pulverized in a ball mill homogenizer, incubated in methanol at 378C overnight, liquid-liquid extracted with ethyl acetate and measured by chromatography techniques (GC-NPD and GC-MS) for confirmation. The concentration of the diazinon in the hair of the exposed animals ranged from 0.11 to 0.26 ng/ mg hair. It was concluded that there is a relationship between the administered dose and the detected pesticide concentration in hair. Finally, it seems that hair analysis may be used to investigate chronic exposure to the pesticide.
Effect of leptin administration on plasma and tissue lipids in alcohol induced liver injury
Authors: Balasubramaniyan V , Manju V , Nalini N
Published: May 2003

Previous studies suggest a possible link between leptin and hepatic inflammation; however the role of leptin in liver diseases remains unclear. The purpose of the present study was to evaluate the effect of leptin on plasma and tissue lipids in experimental hepatotoxicity. Administering ethanol (6.32 g/kg body weight) to 4-weekold healthy mice for 45 days resulted in significantly elevated levels of plasma and tissue phospholipids, triglycerides and free fatty acids as compared with those of the control animals. Subsequent to the experimental induction of hepatotoxicity (i.e., the initial period of 30 days) exogenous leptin was simultaneously administered (230 mg/kg body weight) every alternate day for 15 days along with the daily dose of alcohol. Leptin administration to control and alcohol-treated mice reduced the weight gain and significantly lowered the levels of plasma and tissue lipids as compared with the untreated control and alcohol supplemented mice. It is postulated that the increase in systemic leptin levels lower the plasma and tissue lipids of alcohol-treated mice, which operates independently of changes in food intake, body weight and the size of the fat stores.
A Comparative Study of Chinese, American and Japanese Nurses’ Perceptions of Ethical Role Responsibilities
Authors: Pang Samantha Mei-che , Sawada Aiko , Konishi Emiko , Olsen Douglas P , Yu Philip LH , Chan Moon-fai , Mayumi Naoya
Published: May 2003

This article reports a survey of nurses in different cultural settings to reveal their perceptions of ethical role responsibilities relevant to nursing practice. Drawing on the Confucian theory of ethics, the first section attempts to understand nursing ethics in the context of multiple role relationships. The second section reports the administration of the Role Responsibilities Questionnaire (RRQ) to a sample of nurses in China (n = 413), the USA (n = 163), and Japan (n = 667). Multidimensional preference analysis revealed the patterns of rankings given by the nurses to the statements they considered as important ethical responsibilities. The Chinese nurses were more virtue based in their perception of ethical responsibilities, the American nurses were more principle based, and the Japanese nurses were more care based. The findings indicate that the RRQ is a sensitive instrument for outlining the embedded sociocultural factors that influence nurses’ perceptions of ethical responsibilities in the realities of nursing practice. This study could be important in the fostering of partnerships in international nursing ethics.