bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear problems with solutions exhibiting a free boundary on the boundary
Authors: Montenegro Marcelo , Dávila Juan
Published: April 2005

We prove existence of nonnegative solutions to

−\mathrm{\Delta }u + u = 0

on a smooth bounded domain

Ω

subject to the singular boundary derivative condition

\frac{\partial u}{\partial \nu } = −u^{−\beta } + \lambda f(x,u)

on

\partial \Omega \cap \{u > 0\}

with

0 < \beta < 1

. There is a constant

\lambda ^{ \ast }

such that for

0 < \lambda < \lambda ^{ \ast }

every nonnegative solution vanishes on a subset of the boundary with positive surface measure. For

\lambda > \lambda ^{ \ast }

we show the existence of a maximal positive solution. We analyze its linearized stability and its regularity. Minimizers of the energy functional related to the problem are shown to be regular and satisfy the equation together with the boundary condition.

Nous démontrons l'existence de solutions

u⩾0

de l'équation

−\mathrm{\Delta }u + u = 0

sur un domaine borné régulier

Ω

avec la condition de Neumann singulière suivante :

\frac{\partial u}{\partial \nu } = −u^{−\beta } + \lambda f(x,u)

sur

\partial \Omega \cap \{u > 0\}

oú

0 < \beta < 1

. Il existe une constante

\lambda ^{ \ast }

telle que pour

0 < \lambda < \lambda ^{ \ast }

, toute solution

u⩾0

s'annule sur une partie du bord, de mesure (surfacique) strictement positive. Pour

\lambda > \lambda ^{ \ast }

, nous démontrons l'existence d'une solution maximale positive. Nous analysons ses propriétés de stabilité linéaire et de régularité. On démontre que les minimiseurs de la fonctionnelle d'énergie associée sont réguliers et vérifient l'équation ainsi que la condition de bord.
Uric acid renal excretion and renal insufficiency in decompensated severe heart failure
Authors: Ochiai Marcelo E. , Barretto Antonio C.P. , Oliveira Múcio T. , Munhoz Robinson T. , Morgado Paulo C. , Ramires José A.F.
Published: April 2005

Objective

To evaluate uric acid renal excretion, hyperuricemia, renal dysfunction, and prognosis in patients with decompensated severe heart failure, as there are few data available.

Methods

One hundred and twenty‐two patients, hospitalized for heart failure decompensation, in NYHA class IV, were classified into 3 groups as follows. Pilot group [ejection fraction (EF)≤0.45, n=16], group 1 (EF≤0.45, n=90), and group 2 (EF>0.45 and valvular dysfunction, n=16). The patients in groups 1 and 2 underwent assessment of creatinine and uric acid clearance before and after pyrazinamide, to estimate uric acid tubular secretion. Uric acid clearance <6.8 mL/min and secretion <170 μg/min were considered reduced. In groups 1 and pilot (n=106), mortality was analyzed by Cox regression model, and the prognostic value of hyperuricemia was assessed by ROC curve.

Results

In groups 1 and 2, respectively, serum uric acid was 511.7 and 422.5 mol/L, and creatinine clearance was 46.7 and 61.4 mL/min. Uric acid clearance (3.2 vs. 3.9 mL/min) and tubular secretion (116 vs. 128 μg/min) were not different, but lower than normal values. In groups 1 and pilot, the 12‐month mortality was 46.4% (CI 95%: 36.7%−56.0%). At end of follow‐up, mortality was associated with impaired creatinine clearance (p<0.001), but not with hyperuricemia (p=0.236).

Conclusions

In patients with decompensated severe heart failure, the tubular secretion and the clearance of uric acid were reduced. Renal dysfunction was associated with mortality, but hyperuricemia was not.
Effects of carvedilol on oxidative stress and chronotropic response to exercise in patients with chronic heart failure
Authors: Castro Pablo , Vukasovic José Luis , Chiong Mario , Díaz‐Araya Guillermo , Alcaino Hernán , Copaja Miguel , Valenzuela Rodrigo , Greig Douglas , Pérez Osvaldo , Corbalan Ramón , Lavandero Sergio
Published: April 2005

Background:

Our previous studies suggest that the increase in heart rate from rest to peak exercise is reduced in patients with chronic heart failure (CHF) and this is associated with increased oxidative stress, as determined by malondialdehyde (MDA) plasma levels.

Aim:

To investigate the effects of carvedilol on the heart rate response to exercise and oxidative stress in patients with CHF.

Methods and results:

Thirty stable NYHA classes II—III CHF patients received carvedilol therapy for 6 months, at a mean maintenance dose of 25 mg (range 6.25—50 mg/day). After treatment, the patients showed a significant improvement in their functional NYHA class (p=0.013), increased left ventricular ejection fraction (LVEF) (24±1.4% to 31±2.3%, p=0.003) and 6‐min walk distance (499±18 to 534±18 m, p=0.03), without changes in the peak VO2. At baseline, norepinephrine (NE) plasma levels increased with exercise (510±51 to 2513±230 pg/mL, p<0.001), and these levels were not affected by carvedilol. Chronotropic responsiveness index (increase in heart rate divided by the increase in NE from rest to peak exercise) was not changed by carvedilol (0.049±0.001 to 0.042±0.001, p=0.6). MDA levels of CHF patients decreased after treatment with carvedilol (2.4±0.2 to 1.1±0.2 μM, p<0.001), without changes in antioxidant enzyme activities.

Conclusions:

Carvedilol treatment in patients with CHF results in reduced oxidative stress without restoration of the chronotropic responsiveness index.
Influence of age and in‐patient care on prescription rate and long‐term outcome in chronic heart failure: a data‐based substudy of the EuroHeart Failure Survey
Authors: Hülsmann Martin , Berger Rudolf , Mörtl Deddo , Pacher Richard
Published: April 2005

Aims

To evaluate the prescription rate of neurohumoral drugs in chronic heart failure patients and the factors influencing prescription rates. Outcomes and their predisposing factors were also investigated.

Methods and results

Of 1482 consecutive patients admitted to 3 Austrian hospitals participating in the EuroHeart Failure Survey, 341 were included in this data‐based substudy. Follow‐up time to evaluate outcome was up to 46 months. The prescription rates of renin–angiotensin (RAAS) antagonists and β‐blockers at the time of discharge were evaluated. The overall prescription rate and dosage were lower than the recommended levels. Hospitals with cardiac care had a significantly higher prescription rate than those without (p<0.001). Patients older than 75 years received significantly less therapy (p<0.001) and a lower dosage of RAAS antagonists (p<0.01) than younger patients. Younger patients were treated more intensively in hospitals with cardiac care (p<0.05). Patients aged >75 years were under‐treated, independent of the hospital (n.s.). Multivariate analysis showed that age was the most influencing factor on survival (X2 15.5, p<0.0001). Additional influencing factors of long‐term survival were type of the ward (X2 7.9, p<0.005) and pharmacologic treatment (X2 6.2, p<0.02).

Conclusion

Patients with chronic heart failure are still under‐treated in clinical practice. Younger patients benefit from hospitals with specialized cardiac care. Elderly patients are obviously under‐treated compared with younger patients. Of several clinical parameters, age was the only independent variable predicting long‐term survival.
Pre‐eclampsia with acute heart failure postpartum as primary manifestation of systemic lupus erythematosus
Authors: Hildbrand P. , Eigenmann C. , Gugger M. , Marti H.P. , Hullin R.
Published: April 2005

Pre‐eclampsia occurs in 2–5% of pregnancies of healthy women. Here, we present a rare case of pre‐eclampsia with overt acute heart failure, which was the primary manifestation of systemic lupus erythematosus with cardiac and renal involvement.
Do dialogues about concepts of pain reduce immigrant patients' reported spread of pain? A comparison between two consultation methods in primary care
Authors: Löfvander Monica B. , Engström Alf W. , Iglesias Edgar
Published: April 2005

Objectives Do dialogues about concepts of pain reduce the reported spread of pain more than the usual consultations?

Setting A 4‐week programme in primary care for immigrants on sick‐leave, aged 16–45 years, containing daily exercises and randomised to either four interviews and dialogues about pain with a female doctor (group A) or the usual consultations with a male doctor (group B).

Methods Two doctors made the first and the last evaluations (before and after the programme) containing diagnostics of tender‐structure locations and depression (yes‐no), and ratings of severity of psychosocial stressors. Anxiety about pain was noted (yes‐no). The patients pointed to their painful areas and these were noted on pain drawings (0–18 fields). Median values were calculated, and non‐parametric statistics were used to test for significant differences between groups and before‐and‐after values, and the correlation between the number of pain drawing fields and clinical variables.

Results Forty‐five persons participated in the whole programme, Group A (8 men, 15 women), group B (7 men, 15 women). Many of them needed an interpreter. Participants in group A had more tender‐structure locations (two vs. one in group B). Nearly half had depression and two‐thirds had serious psychosocial stressors. Almost all reported anxiety about pain at the start, but afterwards significantly fewer in group A (22 vs. 16, p < 0.05). In both groups, the number of pain drawing fields decreased significantly from, in median, eight to four (p < 0.001), particularly among the women (A: p < 0.05 vs. B: p < 0.01). Some very distressed participants reported more spread of pain than at the start. Reduced spread of pain was not significantly correlated to any clinical variable.

Conclusions Particularly the women in both consultation groups demonstrated much less spread of pain after treatment, despite similar clinical findings and less anxiety about pain in group A. The initially wide spread of pain may thus have been a way of communicating with the doctors.
Adding propacetamol to ketorolac increases the tolerance to painful pressure
Authors: Romundstad Luis , Stubhaug Audun , Niemi Geir , Rosseland Leiv Arne , Breivik Harald
Published: April 2005

Combining an NSAID and paracetamol (acetaminophen) has in some studies given superior analgesia compared with the single drugs. In other trials no additive effect has been found. We have investigated the effect of this drug combination on the pressure pain tolerance threshold (PPTT), a reproducible correlate to clinical pain.

The aim of this double blind, randomised, placebo controlled, crossover study was to evaluate the effect of i.v. propacetamol 2 g (=paracetamol 1 g) and ketorolac 30 mg, individually and in combination, on PPTT in 16 volunteers on four separate days. PPTT was measured 15 min before and at 45, 60, 90 and 150 min after the start of test drug administration. The pressure stimuli were applied on the base of a fingernail, increasing by 30 kPa/s until the pressure pain tolerance threshold was reached.

For the total observation period (150 min), only the combination (propacetamol + ketorolac) increased significantly PPTT compared with baseline (P < 0.04), while PPTT decreased significantly after placebo (P < 0.01). The combination (propacetamol + ketorolac) and ketorolac alone increased PPTT compared with placebo (combination vs. placebo and ketorolac vs. placebo, P < 0.001) and with propacetamol (combination vs. propacetamol and ketorolac vs. propacetamol, P < 0.001). The combination was significantly better than ketorolac alone (P < 0.04). After propacetamol 2 g, PPTT did not change significantly neither compared with placebo or baseline.

Conclusions Tolerance to repeated painful pressure (PPTT) decreased after placebo. Ketorolac 30 mg caused an increase in PPTT compared with placebo but not with baseline. Adding propacetamol 2 g to ketorolac 30 mg significantly increased PPTT. These findings support the practice of combining paracetamol with an NSAID for relief of acute pain.
Training medical students to manage a chronic pain patient: both knowledge and communication skills are needed
Authors: Leila Niemi‐Murola , Pirkko Heasman , Eeva Pyörälä , Eija Kalso , Reino Pöyhiä
Published: April 2005

Most studies concerning pain education of undergraduate medical students focus on knowledge, but little is known about the interviewing skills and pain evaluation. At the end of the fifth study year and at the beginning of the sixth year the students were asked to answer an electronical questionnaire to evaluate how the IASP curriculum on pain had been covered during the studies. In addition, the interviewing skills of the fifth year medical students were assessed using an objective structured clinical examination (OSCE). The students met a standardized patient suffering from postherpetic neuralgia, who was instructed to express depressive and exhausted feelings.

A total of 97 students received the questionnaire and 35% responded with identification. All students answering the IASP questionnaire evaluated teaching of postherpetic pain and antidepressant treatment as sufficient. OSCE appeared as a feasible instrument in the assessment of chronic pain education. Eighty‐eight percent of the students made the correct diagnosis. However, only 35% asked about sleep disturbances and 16% about depression.

When developing a curriculum on pain education, attention should be paid to pedagogic methods about helping the students to implement the learned knowledge in their practice. Formative assessment of both knowledge and skills is essential for the development of a functional pain curriculum.
Smoking cessation guidelines: evidence-based recommendations of the French Health Products Safety Agency
Authors: Le Foll B. , Melihan-Cheinin P. , Rostoker G. , Lagrue G. ,   for the working group of AFSSAPS
Published: April 2005

Tobacco use is the leading preventable cause of death in developed countries. Millions of smokers are willing to stop, but few of them are able to do so. Clinicians should only use approaches that have demonstrated their efficacy in helping patients to stop smoking. This article summarizes the evidence-based major findings and clinical recommendations for the treatment of tobacco dependence of the French Health Products Safety Agency (AFSSAPS). Clinicians should enquire about the smoking status of each patient and provide information about health consequence of smoking and effective treatments available. These treatments include counseling (mainly individual or social support and behavioral and cognitive therapy) and pharmacological treatment with either nicotine replacement therapy (NRT) or bupropion LP. Pharmacological treatments should be used only for proven nicotine dependence, as assessed by the Fagerstrom test for Nicotine Dependence. The choice of pharmacologic treatment depends of the patient's preference and history and of the presence of contra-indications. The clinician should start with a single agent, but these treatments may be used in combination. Smoking behavior is a chronic problem that requires long-term management and follow-up. Access to intensive treatment combining pharmacological treatment and extensive behavioral and cognitive therapy should be available for highly dependent patients.
Are eye movement abnormalities indicators of genetic vulnerability to schizophrenia?
Authors: Boudet C. , Bocca M.L. , Chabot B. , Delamillieure P. , Brazo P. , Denise P. , Dollfus S.
Published: April 2005

Fifty to eighty-five percent of schizophrenic patients are impaired on ocular pursuit paradigms. However, results regarding the relatives are more discordant. The aim of this study was to investigate whether eye movement disorders could be a vulnerability marker of schizophrenia.

Method

Twenty-one schizophrenic patients (DSM-IV), 31 first-degree relatives of those patients without schizophrenic spectrum disorders, and two groups of healthy controls matched by age and sex were included. Three oculomotor tasks (smooth pursuit, reflexive saccades and antisaccades) were used.

Results

Patients had a lower averaged gain (P = 0.035) during smooth pursuit than controls, made less correct visually guided saccades (P < 0.001) and more antisaccades errors (P = 0.002) than controls. In contrast, none of the comparison between the relatives and their controls was significant.

Conclusions

Schizophrenic patients were impaired on smooth pursuit and antisaccade paradigms. None of these impairments was, however, observed in their first-degree relatives. Our results suggest that the eye movement parameters tested could not be considered as vulnerability markers for schizophrenia.
Fluid-attenuated inversion-recovery MR imaging in schizophrenia-associated with idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome)
Authors: Miyaoka Tsuyoshi , Yasukawa Rei , Mihara Takumi , Mizuno Shoichi , Yasuda Hideaki , Sukegawa Tsuruhei , Hayashida Maiko , Inagaki Takuji , Horiguchi Jun
Published: April 2005

Background

Patients with schizophrenia show a significantly higher frequency of hyperbilirubinemia the patients suffering from other psychiatric disorders and the general healthy population. The objective of the current study was to determine whether patients with schizophrenia-associated idiopathic unconjugated hyperbilirubinemia (Gilbert's syndrome, GS) have specific changes in signal intensities on fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) images.

Methods

Axial 5-mm-thick FLAIR MR images from schizophrenia patients with GS (n = 18) and schizophrenia patients without GS (n = 18), all diagnosed according to DSM-IV criteria, were compared with age- and sex-matched non-psychiatric controls (n = 18). Signal intensities in the hippocampus, amygdala, caudate, putamen, thalamus, cingulate gyrus, and insula were graded relative to cortical signal intensity in the frontal lobe.

Results

Compared to both schizophrenia patients without GS and normal controls, the schizophrenia patients with GS showed significantly increased signal intensities in almost all regions studied.

Conclusion

Patients with schizophrenia-associated GS have specific changes of signal intensities on FLAIR MR images, suggesting that schizophrenia with GS produces changes in the fronto-temporal cortex, limbic system, and basal ganglia.
Prospective study of hippocampal volume and function in human subjects treated with corticosteroids
Authors: Hájek Tomáš , Kopeček Miloslav , Preiss Marek , Alda Martin , Höschl Cyril
Published: April 2005

Purpose.

Decreased hippocampal volume reported in neuropsychiatric and endocrine disorders is considered a result of putative neuronal damage mediated by corticosteroids. This is the first prospective study of hippocampal volume and function in patients treated with corticosteroids.

Methods.

14 subjects treated systemically with prednisone or betamethasone for dermatological or rheumatic disorders underwent prospective neurocognitive testing (Auditory Verbal Learning Test—AVLT, Trail Making Test—TMT, Digit Span—DS) and nine of them also repeated magnetic resonance volumetry.

Results.

The mean duration of treatment between the first and the second assessment was 73 ± 38 days with mean daily dose of 37 ± 17 mg prednisone and 193 ± 29 days, with mean daily dose of 24 ± 15 mg prednisone between the first and the third assessment. There was a trend towards decreases in total AVLT scores and an improvement in the TMT and DS, but no significant changes in the volumes of the right or the left hippocampi between the assessments. Prednisone dose did not correlate with the hippocampal volume change.

Conclusion.

We observed a trend for decline in verbal memory despite improvement in psychomotor speed, attention/working memory and no macroscopic hippocampal volume changes during 36–238 days of treatment with therapeutic doses of corticosteroids.
The D2dopamine receptor (DRD2) gene is associated with co-morbid depression, anxiety and social dysfunction in untreated veterans with post-traumatic stress disorder
Authors: Lawford Bruce R. , Young Ross , Noble Ernest P. , Kann Burnett , Ritchie Terry
Published: April 2005

Objective.

To identify clusters of patients with post-traumatic stress disorder (PTSD) according to symptom profile and to examine the association of the A1 allele of the D2dopamine receptor (DRD2) gene with these clusters.

Method.

Fifty-seven untreated Caucasian Vietnam veterans with PTSD were administered the General Health Questionnaire-28 (GHQ) and the Mississippi Scale for combat-related PTSD. DRD2 allelic status was determined by PCR.

Results.

Subjects with the DRD2 Al allele compared to those without this allele had significantly higher scores on GHQ 2 (anxiety/insomnia), GHQ 3 (social dysfunction) and GHQ 4 (depression). Cluster analysis of the GHQ data identified two primary groups. A high psychopathology cluster (cluster 3), featured by high co-morbid levels of somatic concerns, anxiety/insomnia, social dysfunction and depression, and a low psychopathology cluster (cluster 1), manifested by the reverse pattern. Scores in each of the four GHQ groups were significantly higher in cluster 3 than cluster 1, as was Mississippi Scale PTSD score. DRD2 A1 allele veterans compared to those without this allele were significantly more likely to be found in the high than the low psychopathology cluster group.

Conclusions.

DRD2 variants are associated with severe co-morbid psychopathology in PTSD subjects.
Modified nicotine metabolism in transgenic tobacco plants expressing the human cytochrome P450 2A6 cDNA
Authors: Dueckershoff Katharina , Unger Matthias , Frank Andreas , Gillam Elizabeth M.J. , Guengerich F. Peter , Warzecha Heribert
Published: April 2005

In this study, the human cytochrome P450 (CYP) 2A6 was used in order to modify the alkaloid production of tobacco plants. The cDNA for human CYP2A6 was placed under the control of the constitutive 35S promoter and transferred into Nicotiana tabacum via Agrobacterium‐mediated transformation. Transgenic plants showed formation of the recombinant CYP2A6 enzyme but no obvious phenotypic changes. Unlike wild‐type tobacco, the transgenic plants accumulated cotinine, a metabolite which is usually formed from nicotine in humans. This result substantiates that metabolic engineering of the plant secondary metabolism via mammalian P450 enzymes is possible in vivo.
Cytokines upregulate vascular endothelial growth factor secretion by human airway smooth muscle cells: Role of endogenous prostanoids
Authors: Stocks Joanne , Bradbury Dawn , Corbett Lisa , Pang Linhua , Knox Alan J.
Published: April 2005

Here, we report that vascular endothelial growth factor (VEGF)‐A secretion by human airway smooth muscle cells was increased by interleukin 1 beta (IL‐1β) and transforming growth factor beta (TGFβ). IL‐1β and TGFβ induced cyclo‐oxygenase (COX)‐2 protein and increased prostaglandin E2 (PGE2). Both IL‐1β and TGFβ increased VEGF‐A165 mRNA and VEGF promoter luciferase construct activity, in addition VEGF‐A protein was inhibited by actinomycin D suggesting transcriptional regulation. The COX inhibitors indomethacin and NS398 inhibited IL‐1β but not TGFβ mediated VEGF‐A production. Furthermore, the effect of the COX inhibitors was overcome by adding exogenous PGE2. In conclusion, IL‐1β increases VEGF‐A secretion by COX‐2 derived PGE2 production whereas TGFβ uses COX‐independent pathways.
Structure and functional role of supercomplexes of IsiA and Photosystem I in cyanobacterial photosynthesis
Authors: Kouřil Roman , Arteni Ana A. , Lax Julia , Yeremenko Nataliya , D‧Haene Sandrine , Rögner Matthias , Matthijs Hans C.P. , Dekker Jan P. , Boekema Egbert J.
Published: April 2005

Cyanobacteria express large quantities of the iron stress‐inducible protein IsiA under iron deficiency. IsiA can assemble into numerous types of single or double rings surrounding Photosystem I. These supercomplexes are functional in light‐harvesting, empty IsiA rings are effective energy dissipaters. Electron microscopy studies of these supercomplexes show that Photosystem I trimers bind 18 IsiA copies in a single ring, whereas monomers may bind up to 35 copies in two rings. Work on mutants indicates that the PsaF/J and PsaL subunits facilitate the formation of closed rings around Photosystem I monomers but are not obligatory components in the formation of Photosystem I–IsiA supercomplexes.
Understanding the enzymology of fibrinolysis and improving thrombolytic therapy
Authors: Longstaff Colin , Thelwell Craig
Published: April 2005

Cardiovascular disease is responsible for 17 million deaths per year but acute myocardial infarction and stroke can be treated with thrombolytics (“clot busters”), which are plasminogen activators. However, despite many years of study and huge investment from the pharmaceutical industry, clinical trials of new drugs have often been disappointing. Part of the problem may be our incomplete understanding of the regulation of plasminogen activation in vivo. We have developed precise in vitro methods and with the application of computer simulations, we hope to improve our understanding of plasminogen activation to facilitate improvements in thrombolytic therapy.
Mass spectrometric identification of a novel phosphorylation site in subunit NDUFA10 of bovine mitochondrial complex I
Authors: Schilling Birgit , Aggeler Robert , Schulenberg Birte , Murray James , Row Richard H. , Capaldi Roderick A. , Gibson Bradford W.
Published: April 2005

Mitochondrial Complex I (NADH:ubiquinone oxidoreductase) consists of at least 46 subunits. Phosphorylation of the 42‐kDa subunit NDUFA10 was recently reported using a novel phosphoprotein stain [Schulenberg et al. (2003) Analysis of steady‐state protein phosphorylation in mitochondria using a novel fluorescent phosphosensor dye. J. Biol. Chem. 278, 27251]. Two smaller Complex I phosphoproteins, ESSS and MWFE, and their sites of modification, have since been determined [Chen et al. (2004) The phosphorylation of subunits of complex I from bovine heart mitochondria. J. Biol. Chem. 279, 26036]. Here we identify the site of phosphorylation in NDUFA10 from bovine heart mitochondria by tandem mass spectrometry. A single phosphopeptide spanning residues 47–60 was identified and confirmed by synthesis to be (47)LITVDGNICSGKpSK(60), establishing serine‐59 as the site of phosphorylation.
The FAXWXXT motif in the carboxyl terminus of Vibrio mimicus metalloprotease is involved in binding to collagen
Authors: Lee Jong-Hee , Ahn Sun-Hee , Lee Eun-Mi , Jeong Seung-Ha , Kim Young-Ok , Lee Sang-Jun , Kong In-Soo
Published: April 2005

We have shown previously that the C‐terminal region of the extracellular metalloprotease of Vibrio mimicus (VMC) is essential for collagenase activity. Here, we demonstrate that deletion of 100 amino acids, but not 67 amino acids, from the C‐terminus of the intact VMC protein (VMC61) abolished the collagenase activity. The intervening 33‐amino acid region contains a repeated FAXWXXT motif that is essential for insoluble type I collagen binding; the isolated 33‐amino acid peptide bound to insoluble type I collagen, while a peptide containing only the first FAXWXXT motif did not. Compared to the VMC61, the 33‐amino acid peptide corresponding to the C‐terminus exhibited a similar binding affinity and a lower binding capacity.
Transglutaminase 2 in the balance of cell death and survival
Authors: Fésüs László , Szondy Zsuzsa
Published: April 2005

Transglutaminase 2 (TG2), a multifunctional enzyme with Ca2+‐dependent protein crosslinking activity and GTP‐dependent G protein functions, is often upregulated in cells undergoing apoptosis. In cultured cells TG2 may exert both pro‐ and anti‐apoptotic effects depending upon the type of cell, the kind of death stimuli, the intracellular localization of the enzyme and the type of its activities switched on. The majority of data support the notion that transamidation by TG2 can both facilitate and inhibit apoptosis, while the GTP‐bound form of the enzyme generally protects cells against death. In vivo studies confirm the Janus face of TG2 in the initiation of the apoptotic program. In addition, they reveal a further role: the prevention of inflammation, tissue injury and autoimmunity once the apoptosis has already been initiated. This function of TG2 is partially achieved by being expressed and activated also in macrophages digesting apoptotic cells and mediating a crosstalk between dying and phagocytic cells.
Molecular characterization of the first satellite DNA with CENP‐B and CDEIII motifs in the bat Pipistrellus kuhli
Authors: Fantaccione Stefania , Pontecorvo Giovanni , Zampella Vincenzo
Published: April 2005

The centromere is an essential structure in the chromosomes of all eukariotes and is central to the mechanism that ensures proper segregation during mitosis and meiosis. The comparison of DNA sequence motifs, organization and kinetocore components from yeast to man is beginning to indicate that, although centromeres are highly variable DNA elements, a conserved pattern of sequence arrangement and function is emerging. We have identified and characterized the first satellite DNA (P.k.SAT) from microbat species Pipistrellus kuhli. The presence of mammalian CENP‐B box and yeast CDEIII box could indicate the participation of P.k.SAT in centromere organization.
Functional regulation of Na+‐dependent neutral amino acid transporter ASCT2 byS‐nitrosothiols and nitric oxide in Caco‐2 cells
Authors: Uchiyama Tomomi , Matsuda Yasuyuki , Wada Miyuki , Takahashi Satoru , Fujita Takuya
Published: April 2005

We describe the regulation mechanisms of the Na+‐dependent neutral amino acid transporter ASCT2 via nitric oxide (NO) in the human intestinal cell line, Caco‐2. Exposure of Caco‐2 cells toS‐nitrosothiol, such asS‐nitroso‐N‐acetyl‐dl‐penicillamine (SNAP) andS‐nitrosoglutathione, and the NO‐donor, NOC12, concentration‐ and time‐dependently increased Na+‐dependent alanine uptake. Kinetic analyses indicated that SNAP increases the maximal velocity (Vmax) of Na+‐dependent alanine uptake in Caco‐2 cells without affecting the Michaelis–Menten constant (Kt). The stimulatory effect was partially eliminated by actinomycin D and cycloheximide. Increased Na+‐dependent alanine uptake by SNAP was partially abolished by the NO scavengers, 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl 3‐oxide sodium salt (carboxy‐PTIO) andN‐(dithiocarboxy)sarcosine disodium salts (DTCS), as well as the NADPH oxidase inhibitor, diphenyleneiodonium. RT‐PCR revealed that Caco‐2 cells expressed the Na+‐dependent neutral amino acid transporter ASCT2, but not the other Na+‐dependent neutral amino acid transporters ATB0,+and B0AT1. These results suggested that functional up‐regulation of ASCT2 by SNAP might be partially associated with an increase in the density of transporter protein via de novo synthesis.
Gene expression and characterization of isoprene synthase from Populus alba
Authors: Sasaki Kanako , Ohara Kazuaki , Yazaki Kazufumi
Published: April 2005

Isoprene synthase cDNA from Populus alba (PaIspS) was isolated by RT‐PCR. This PaIspS mRNA, which was predominantly observed in the leaves, was strongly induced by heat stress and continuous light irradiation, and was substantially decreased in the dark, suggesting that isoprene emission was regulated at the transcriptional level. The subcellular localization of PaIspS protein with green fluorescent protein fusion was shown to be in plastids. PaIspS expressed in Escherichia coli was characterized enzymatically: it had an optimum pH of approximately 8.0, and an optimum temperature 40 °C. Its preference for divalent cations for its activity was also studied.
Nitric oxide, cytochrome c oxidase and myoglobin: Competition and reaction pathways
Authors: Giuffrè Alessandro , Forte Elena , Brunori Maurizio , Sarti Paolo
Published: April 2005

It is relevant to cell physiology that nitric oxide (NO) reacts with both cytochrome oxidase (CcOX) and oxygenated myoglobin (MbO2). In this respect, it has been proposed [Pearce, L.L., et al. (2002) J. Biol. Chem. 277, 13556–13562] that (i) CcOX in turnover out‐competes MbO2 for NO, and (ii) NO bound to reduced CcOX is “metabolized” in the active site to nitrite by reacting with O2. In contrast, rapid kinetics experiments reported in this study show that (i) upon mixing NO with MbO2 and CcOX in turnover, MbO2 out‐competes the oxidase for NO and (ii) after mixing nitrosylated CcOX with O2 in the presence of MbO2, NO (and not nitrite) dissociates from the enzyme causing myoglobin oxidation.
An evaluation of the implicit management procedure used for some ICES roundfish stocks
Authors: Kell L.T. , Pilling G.M. , Kirkwood G.P. , Pastoors M. , Mesnil B. , Korsbrekke K. , Abaunza P. , Aps R. , Biseau A. , Kunzlik P. , Needle C. , Roel B.A. , Ulrich-Rescan C.
Published: April 2005

This paper describes a simulation study that evaluated the performance of the scientific advisory process used by ICES to recommend total allowable catches (TACs) for roundfish stocks. A “management strategy evaluation” approach is used, involving development of an operating model to represent the underlying reality, and an observation model to generate pseudo data that are then used within a management procedure. The management procedure comprises an assessment that uses data to estimate parameters of interest and a decision rule to derive TAC recommendations for the following year. There are two important results: including realistic sources and levels of uncertainty can result in far from optimal management outcomes based on the current procedures; and current ICES biomass and fishing mortality reference points are not always consistent, and several are clearly inappropriate. This is because the types of projection used by ICES do not incorporate important lags between assessing stock status and implementing management measures, and they also ignore important sources of uncertainty about the actual dynamics, as well as our ability to collect data and implement management regulations (i.e. model, measurement, and implementation error, respectively). The simulation approach also showed that better management is not necessarily going to be achieved by improving the assessment, because even with a perfect assessment (where the simulated working group knew stock status perfectly), stocks may crash at fishing levels that standard stochastic projections would suggest were safe. It is proposed that, in future, operating models that represent the best available understanding of the actual system dynamics be used to evaluate models and rules considered for application. These operating models should capture the plausible range of characteristics of the underlying dynamics, but not necessarily model their full complexity. In general, they will be more complex than those used by assessment working groups, so developing management procedures that are robust to a broad range of uncertainty. However, the models and rules used as part of the management procedure should be simpler than those used at present.
An integrated growth study for North Atlantic albacore (Thunnus alalunga Bonn. 1788)
Authors: Santiago J. , Arrizabalaga H.
Published: April 2005

The growth of North Atlantic albacore (Thunnus alalunga) was studied using three methods. Spines collected during a fishing season (n = 761) were read and used to estimate growth parameters. Additional growth estimates were obtained by applying MULTIFAN to quarterly size frequency distributions of total international catch for the period 1990–1999 as well as using tag-recapture data (n = 314). In the case of spines and tagging, models that allowed for individual variability in growth were evaluated. In the analysis with size frequency distributions, a model that allowed for seasonal growth and age-dependent standard deviation around the mean lengths-at-age was used. Growth estimates were consistent among the different methods, and a combined model based on ageing derived from spines and tagging data is proposed as the most comprehensive descriptor of growth of North Atlantic albacore.
Monitoring utilization and need for obstetric care in the highlands of Guatemala
Authors: Bailey P. , de Bocaletti E. , Barrios G. , de Cross Y.
Published: April 2005

Objective

To monitor changes in the utilization and need for obstetric care between 1995 and 1998 at three hospitals in the highlands of Guatemala.

Methods

We collected data on 5300 obstetric admissions from maternity registries and selected 10 indicators to measure intermediate outcomes.

Results

Utilization of services increased at some or all hospitals as measured by the number of obstetric admissions, proportion of births in facilities, and cesarean deliveries as a proportion of all births. We observed increases in the proportion of women expected to have obstetric complications who were treated at each hospital and in the proportion of women with obstetric complications who were referrals. The changes in patient profile reflect increased service utilization and accessibility among women who traditionally used the health system the least.

Conclusions

Positive changes in these indicators are likely to be associated with a reduction in maternal mortality. Without a control area, we cannot be sure of a cause and effect relationship between outcomes and interventions, nevertheless, maternity registry data offer an inexpensive source of information for facilities to monitor changes.
Parasuicide in pregnancy
Authors: Marishane T. , Moodley J.
Published: April 2005

Parasuicide is a significant risk factor for completed suicide. Furthermore, suicide is emerging as an important cause of maternal death, especially among young mothers. There are no published reports of parasuicide in pregnancy from poor countries. Three cases are reported to highlight this issue and to demonstrate management options available to health professionals working in the field of women's health.
Extensor Carpi Ulnaris Problems at the Wrist–Classification, Surgical Treatment and Results
Authors: ALLENDE C. , LE VIET D.
Published: April 2005

Twenty-eight extensor carpi ulnaris lesions at the wrist were treated surgically between 1990 and 2002. Fifteen patients had an isolated extensor carpi ulnaris tenosynovitis or tendinopathy, five had extensor carpi ulnaris dislocation, four had an extensor carpi ulnaris subluxation and four had an extensor carpi ulnaris rupture. Seventeen patients first developed their symptoms while playing sports.

At a mean follow-up of 23 months, twenty-two patients had returned to their previous activities. Seven of the 27 patients had lost more than 30% of their grip strength and five had restricted wrist motion. Two needed an extensor carpi ulnaris tenolysis.

Pure isolated extensor carpi ulnaris lesions are rare and associated ulnar sided lesions (eleven triangular fibrocartilage complex tears and four lunotriquetral ligament tears), as well as possible predisposing factors (seven anomalous tendon slips, four ulnar styloid non-unions and one flat extensor carpi ulnaris tendon groove), were frequent. A classification of extensor carpi ulnaris tendon and subsheath lesions was developed to allow the surgeon to adequately evaluate the different components of these lesions.
Long-Term Follow-Up of Surgical Treatment for Thumb Duplication
Authors: LARSEN M. , NICOLAI J. P. A.
Published: April 2005

There are few long-term follow-up reports concerning the treatment of thumb duplication. We reviewed the treatment of 19 of 74 patients treated at our institution between 1956 and 2002. The average follow-up was 22 (range, 7 years to 35 years) years. Satisfactory function was achieved in 18 thumbs and cosmesis in 12 thumbs. Six thumbs were cold-intolerant at this late follow-up. Pinch strength was similar to the contralateral normal thumbs. Collateral ligament repair did not significantly contribute to joint stability. An objective method of postoperative evaluation showed good results in five, fair results in 12 and poor results in two thumbs.
Chronic Sclerosing Osteomyelitis of a Metacarpal
Authors: KELKAR A. S. , MALSHIKARE V. A.
Published: April 2005

Chronic sclerosing osteomyelitis in a metacarpal is presented. Bacterial cultures were negative, and radiographs and an isotope scan were non-specific. Histopathological assessment confirmed the diagnosis. Iliac bone grafting resulted in symptomatic relief to the patient.
Characterization of a chronic infection in an internally‐stabilized segmental defect in the rat femur
Authors: Chen Xinqian , Tsukayama Dean T. , Kidder Louis S. , Bourgeault Craig A. , Schmidt Andrew H. , Lew William D.
Published: April 2005

The aim of this study was to characterize a new model of chronic osteomyelitis with clinically relevant features. A segmental defect of critical size was surgically created in the rat femur, stabilized with a polyacetyl plate and Kirschner wires, and contaminated with bacteria. The animals were allowed to recover while the contamination progressed to a chronic infection. At a later point in time, the defect was surgically débrided without removing the implant. Further treatments of interest, such as antibiotic therapy or application of an osteogenic agent, could be introduced at this time. To implement this model, an initial experiment was performed to determine the bacterial inoculum and time from contamination that would reliably result in an infected defect without causing excessive bone damage by the time débridement surgery was performed. The number of recovered bacteria, degree of radiographic bony lysis, and torsional stiffness of the defect fixation were measured in 192 rats as a function of 4 inocula of Staphylococcus aureus (103, 104, 105 or 106 CFUs) and 4 times from contamination (1, 2, 3 or 4 weeks). A 104 CFU inoculum over 2 weeks was found to consistently create an infection without severe lysis and loss of fixation stability. Based on these values, a second experiment was performed in 96 rats to characterize the débrided defect over time (2, 4, 8 and 12 weeks after débridement), with and without 4 weeks of the antibiotic ceftriaxone, in terms of the same outcome variables. Infection was persistent in all animals in spite of débridement and antibiotic therapy. Antibiotic therapy did not reduce the degree of bony lysis. Compared with animals not given antibiotic, bacterial counts significantly decreased during the period of antibiotic therapy, but then rebounded to significantly higher levels at 12 weeks. This model allows us to perform further studies on differing regimens of antibiotic therapy and their relationship to surgical débridement, and on the efficacy of osteogenic agents in the presence of infection. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Tendon reattachment to a metallic implant using an allogenic bone plate augmented with rhOP‐1 vs. autogenous cancellous bone and marrow in a canine model
Authors: Higuera Carlos A. , Inoue Nozomu , Lim Jonathan S. , Zhang Renwen , Dimaano Nena , Frassica Frank J. , Chao Edmund Y. S.
Published: April 2005

Functionality of endoprosthetic reconstruction may be improved through secure and lasting soft tissue reattachment directly to the metallic implant surface. Tendon reattachment to the metallic surface of a titanium implant (enhanced tendon anchor, ETA) using autogenous bone plate as an interpositional structure between the tendon and metal, augmented with autogenous bone chips and marrow, provided successful mechanical and functional outcome. However, preparation of the autogenous bone plate is not practical in a clinical setting, but application of an allogenic bone plate could be an alternative. The autogenous cancellous bone and marrow may also be substituted by bone growth factors so that no autogenous bone graft is required. We hypothesized that the reconstitution of the direct tendon–bone insertion morphology in tendon reattachment to metallic implant could be achieved using allogenic cancellous bone plate augmented with autogenous cancellous bone and marrow, and that the autogenous bone grafts could be replaced by recombinant human osteogenic protein‐1 (rhOP‐1). In two canine groups the supraspinatus tendon was reattached unilaterally to a modified ETA implant with a highly porous metallic surface known as Tritanium Dimensionalized MetalTM. Allogenic bone plates saturated with rhOP‐1‐collagen putty were used in the OP‐1 (OP) group, while plates saturated with autogenous cancellous bone and marrow were used in the bone marrow (BM) group. Functional, radiographical, mechanical and histomorphological analysis results were compared between both groups. At 15 weeks, gait analysis showed 78% and 81% recovery of preoperative weight‐bearing in OP and BM groups, respectively. The calcified area around the tendon in OP group was 5.2 times larger than that in BM group (p < 0.001). The ultimate tensile strength of the reattachment was 24% and 38% of the intact contralateral side in OP and BM groups, respectively, without significant difference between them. There was evidence of tendon–bone insertion transitional zones, tissue ingrowth and adhesion to the metallic surface in both groups. In conclusion, the use of the allograft combined with rhOP‐1 had a similar effect as combined with autogenous cancellous bone and marrow in the tendon reattachment to the metallic surface. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
POLICY AND PRINCIPLE IN DRUGS MANSLAUGHTER CASES
Authors: Williams Rebecca
Published: April 2005

OVER the past 30 years, in a series of cases where one person has been in some way involved in the death of another from a drugs overdose, the courts have struggled to explain the basis on which the first person should be guilty of manslaughter. Two connected issues have arisen: where, as is normally the case, D has been charged with unlawful act, or constructive, manslaughter, an unlawful act on D’s part has had to be identified; and a chain of causation between D’s act and the death has had to be established.
OBJECTIONS AND EXCEPTIONS: THE PALINGENESIA OF D.43.24.17
Authors: Rodger Alan
Published: April 2005

A, the owner of a house in Rome, hears that, when carrying out some building work, C intends to interfere with one of the walls. A gives notice to C that he objects to the work (prohibet). Despite this, C goes ahead with it. Or else, being aware that A would object if he knew, C deliberately carries out the work while A is away at his seaside villa at Baiae. In the first situation C is regarded as doing the work by force (vi); in the second he does it clandestinely (clam). In either event, the praetor will grant A an interdict ordering C to put the wall back to its original state so that the parties’ rights may be determined and any appropriate security given: quod vi aut clam factum est … restituas.
PRE-CONTRACTUAL MISREPRESENTATION AND THE LIMITS OF THE PRINCIPLE IN WITH V. O’FLANAGAN
Authors: Bigwood Rick
Published: April 2005

THE English Court of Appeal decided With v. O’Flanagan in 1936. The case concerns the interesting phenomenon of “supervening falsification” within the law of pre-contractual misrepresentation. Such a phenomenon occurs when a representation, though perfectly true when made, and unknown to representee throughout, has nevertheless become substantially false by the time it induces the representee to enter into the contract in question. The problem of supervening falsification potentially arises whenever there is an (appreciable) interval of time between the moment when a representation is made and the time when the party to whom it was made (reasonably) altered his position on the faith of it.
DO CONSTITUTIONAL CONVENTIONS BIND?
Authors: Jaconelli Joseph
Published: April 2005

CONSTITUTIONAL conventions are to be found in political and legal systems of very different types. Not surprisingly, they exist in considerable abundance in those systems—the prime example is the United Kingdom—the affairs of which are ordered by an unwritten constitution. Familiar instances of constitutional conventions in British government include the following: that the Monarch is required to appoint as Prime Minister the person best placed to command a majority in the House of Commons; that governments are to resign when defeated on a vote of no confidence; that the judicial members of the House of Lords refrain from indulging in party political debate in the chamber; and that ministers are to resign from office after displaying an (admittedly indeterminate) degree of mismanagement of their departments. The preconditions of the existence of any particular constitutional convention are set out in a well-known passage by Sir Ivor Jennings.