bluuebunny/crossref_metadata_2025 huggingface dataset:
Immediate Computed Tomography Scanning of Acute Stroke Is Cost-Effective and Improves Quality of Life
Authors: Wardlaw Joanna M. , Seymour Janelle , Cairns John , Keir Sarah , Lewis Steff , Sandercock Peter
Published: October 2004

Background and Purpose—

Stroke is very common, but computed tomography (CT) scanning, an expensive and finite resource, is required to differentiate cerebral infarction, hemorrhage, and stroke mimics. We determined whether, and in what circumstances, CT is cost-effective in acute stroke.

Methods—

We developed a decision tree representing acute stroke care pathways populated with data from multiple sources. We determined the effect of diagnostic information from CT scanning on functional outcome, length of stay, costs, and quality of life during 5 years for 13 alternative CT strategies (varying proportions and types of patients and rapidity of scanning).

Results—

For 1000 patients aged 70 to 74 years, the policy “scan all strokes within 48 hours” cost £10 279 728 and achieved 1982.3 quality-adjusted life years (QALYs). The most cost-effective strategy was “scan all immediately” (£9 993 676 and 1982.4 QALYs). The least cost-effective was “scan patients on anticoagulants and those in a life-threatening condition immediately and the rest within 14 days” (£12 592 666 and 1931.8 QALYs). “Scan no patients” reduced QALYs (1904.2) and increased cost (£10 544 000).

Conclusion—

Immediate CT scanning is the most cost-effective strategy. For the majority of acute stroke patients, increasing independent survival by correct early diagnosis, ensuring appropriate subsequent treatment and management decisions, reduced costs of stroke and increased QALYs.
Genomics of Preconditioning
Authors: Stenzel-Poore Mary P. , Stevens Susan L. , Simon Roger P.
Published: October 2004

Brief episodes of ischemia can protect against subsequent damaging ischemic events; however, the molecular mechanisms responsible for protection are poorly understood. Identifying genes involved in this process could provide insight into cell survival and treatment of stroke. We developed a murine model of ischemic preconditioning and subsequent stroke and used gene expression profiling to identify genes that may be involved in neuroprotective pathways. Middle cerebral artery occlusions were performed in mice for 15 minutes. (preconditioning), 60 minutes (stroke), or 15 minutes, followed 72 hours later with 60 minutes (preconditioning plus stroke) of middle cerebral artery occlusions. RNA from a region of cortex that is protected by ischemic preconditioning was hybridized to oligonucleotide microarrays. Follow-up experiments used patch clamp to examine cell conductance in cultured neurons exposed to oxygen–glucose deprivation. Stroke, ischemic preconditioning, and ischemic preconditioning plus stroke all induced gene changes that overlapped little among conditions. Stroke induced robust upregulation of gene expression whereas preconditioning followed by stroke resulted in a marked downregulation. Genes upregulated by stroke suggested activation of stress/inflammatory pathways and increased metabolism and ion channel function. Preconditioning tended to decrease genes involved in these pathways. Follow-up experiments show that preconditioning decreased voltage-gated potassium currents in vitro and increased bleeding time. Preconditioning reprograms the response to ischemic injury via transcriptional changes that may suppress metabolic pathways and immune responses, reduce ion channel activity, and decrease blood coagulation. These changes resemble evolutionarily conserved responses to decreased blood flow and oxygen availability that occur during hibernation.
Magnitude and Role of Wall Shear Stress on Cerebral Aneurysm
Authors: Shojima Masaaki , Oshima Marie , Takagi Kiyoshi , Torii Ryo , Hayakawa Motoharu , Katada Kazuhiro , Morita Akio , Kirino Takaaki
Published: October 2004

Background and Purpose—

Wall shear stress (WSS) is one of the main pathogenic factors in the development of saccular cerebral aneurysms. The magnitude and distribution of the WSS in and around human middle cerebral artery (MCA) aneurysms were analyzed using the method of computed fluid dynamics (CFD).

Methods—

Twenty mathematical models of MCA vessels with aneurysms were created by 3-dimensional computed tomographic angiography. CFD calculations were performed by using our original finite-element solver with the assumption of Newtonian fluid property for blood and the rigid wall property for the vessel and the aneurysm.

Results—

The maximum WSS in the calculated region tended to occur near the neck of the aneurysm, not in its tip or bleb. The magnitude of the maximum WSS was 14.39±6.21 N/m
2
, which was 4-times higher than the average WSS in the vessel region (3.64±1.25 N/m
2
). The average WSS of the aneurysm region (1.64±1.16 N/m
2
) was significantly lower than that of the vessel region (
P
<0.05). The WSSs at the tip of ruptured aneurysms were markedly low.

Conclusions—

These results suggest that in contrast to the pathogenic effect of a high WSS in the initiating phase, a low WSS may facilitate the growing phase and may trigger the rupture of a cerebral aneurysm by causing degenerative changes in the aneurysm wall. The WSS of the aneurysm region may be of some help for the prediction of rupture.
The Collapse of East European Communism and the Repercussions within the Soviet Union (Part 2)
Authors: Kramer Mark
Published: October 2004

This is the second part of a three-part article that looks at the collapse of Communism in Eastern Europe and the repercussions of those events in the Soviet Union. The first part focused on the “direct” spillover from Eastern Europe into the Soviet Union, whereas this segment examines the “indirect” spillover, which took four forms:(1) the discrediting of Marxist-Leninist ideology, (2) the heightened sense of the Soviet regime's own vulnerability, (3) the diminished potential for the use of force in the USSR to curb internal unrest, and (4) the “demonstration effect” and “contagiousness” of regime change and democratization in Eastern Europe. These factors together made it considerably more difficult for Gorbachev to prevent the Soviet Union from unraveling. The final part of the article will be published in the next issue of the journal.
Is Imbibing Al-khamr (Intoxicating Drink) for Medical Purposes Permissible by Islamic Law?
Authors: Deuraseh Nurdeen
Published: October 2004

In this article attempts are made to study one of the important topics that has been widely discussed in Islamic legal literature, namely al-tadawi bi al-muharramat (treatment with forbidden things), with special reference to al-khamr (intoxicating drink). In this regard, there are two different opinions of Muslim jurists regarding the use of intoxicating drink (al-khamr) for medical purposes. The majority of Muslim jurists are of the opinion that treatingdisease with forbidden things is unlawful. As such, they did not allow the use of intoxicating drink for any reason, including its use as a remedy, or to quench thirst, even if there are no other permissible fluids to drink. On the other hand, a few Muslim jurists did allow the use of an intoxicating drink as a remedy, or to quench thirst if no other permissible fluid is available.
Monastic Reading and Learning in eighteenth-century Bilād al-Šām: Some Evidence from the Monastery of al-Šuwayr (Mount Lebanon)
Authors: Walbiner Carsten-Michael
Published: October 2004

A thematic analysis of the manuscripts which were read, copied and written by the monks, the paper raises the issue of education and knowledge amongst the members of the Greek Catholic congregation of the Basilians of al-Šuwayr (Mount Lebanon) during the 18th century, a time in which the order constituted an intellectual centre in Syria, although its influence remained mainly restricted to the own communiy. Despite all efforts the level of knowledge remained—compared with European standards—low. But the monks nevertheless developed a basic attitude, which was important for the introduction of modernity to the Arab world in the 19th century. They had broad interests beyond the narrow limits of their own religion and did not assume from the start a disapproving attitude towards the knowledge and inventions of the West. These were decisive preconditions for a process of learning that had become imperative if the Orient wanted to close the quickly widening scientific gap between East and West.
Perceptions of a New Era? Historical Writing in Early Ottoman Damascus
Authors: Meier Astrid
Published: October 2004

The year 922/1516-7 is usually treated as an important turning point in the history of Bilād al-Šām. The Ottoman conquest initiated change in various fields which has been the focus of much scholarly attention. However, it is still difficult to understand in what ways the new Ottoman subjects perceived these changes, especially in terms of allegiance to the ruling dynasties. To trace the attitudes of different persons and groups, scholars have often turned to the rich body of contemporary historical writing and used it as a source of information. In this article, which is centred on Ottoman Damascus, I argue that chronicles and biographical collections themselves are important witnesses of change and worth to be studied in their own right. As a step towards a more comprehensive understanding of the social uses of knowledge, I suggest that we need to enquire further into the significance of melancholy and solitude in Ottoman historical writing.
UK Savings and Pensions
Authors: Barrell Ray
Published: October 2004

The lack of savings by the UK personal (and private) sector has been a matter of concern to us for some time, in part because it has been clear that inadequate provision has been made for future pension liabilities. The recently published Turner report has highlighted this problem and suggested that on current commitments some 5.2 per cent more of GDP needs to be directed to pensioners in 2050 than is currently the case. Assets have to be built up to provide this extra income, and increased saving is necessary in order to do this. In this note we consider the macroeconomic impacts of building up assets to ensure that the increasing allocation of income to pensioners that an aging population may require is managed efficiently.
Is Mass Higher Education Working? Evidence from the Labour Market Experiences of Recent Graduates
Authors: Elias Peter , Purcell Kate
Published: October 2004

This paper uses a variety of recent sources of information to explore the labour market experiences of those who gained a degree in the 1980s and 1990s. Specifically, we address the issue of ‘overeducation’ — the view that the expansion of higher education in the 1990s created a situation in which increasing numbers of graduates were unable to access employment that required and valued graduate skills and knowledge. Two complementary approaches to this issue are adopted. We review available evidence on the graduate earnings premium and change in the UK occupational structure, and we conduct a detailed examination of the earnings and characteristics of jobs done by a large sample of 1995 graduates seven years after graduation.

We conclude that, while there may have been a decline from the high premium enjoyed by older graduates, for those who graduated in 1995 the average premium was holding up well, despite the expansion. Although we found differences between established graduate occupations and the newer areas of graduate employment, our evidence suggests that the development of new technical and managerial specialisms and occupational restructuring within organisations has been commensurate with the availability of an increased supply of highly qualified people.
The Rate of Return to Teaching: How does it Compare to other Graduate Jobs?
Authors: Dolton Peter , Chung Tsung-Ping
Published: October 2004

The problem of recruiting graduates into the teaching profession and retaining them has bedevilled recent UK governments. An obvious question to ask is why is teaching so relatively unattractive for graduates. This paper presents a careful analysis of this problem. We compare the earnings of qualified teachers who choose to teach with the ‘opportunity wage’ for those who do not teach. We find that the ‘rate of return on career choice’ for teachers has been declining for both men and women over the past 25 years although teaching is still relatively well paid for women. From our net present value analysis we estimate that males who enter teaching lose, on average, earnings of £40,000 to £67,000 over their lifetime while females could stand to gain average earnings of £42,000 to £65,000 if they opted to become school teachers.
Cam-clay and hydraulic conductivity diagram relations in consolidated and sheared clay-matrices
Authors: Dudoignon P. , Gélard D. , Sammartino S.
Published: October 2004

Image analyses, carried out on thin sections made in consolidated and sheared kaolinite test pieces, allow the identification of three ‘microstructural domains’: (1) the initial isotropic matrix; (2) a partly anisotropic matrix resulting from simple particle arrangement; and (3) an anisotropic matrix resulting from rearrangement plus flattening and delamination of particles.

In order to explain the micromechanisms of the clay matrix behaviour, this paper proposes to link the ‘microstructural domains’ represented in the e vs. log p Cam-clay diagram and domains of hydraulic conductivity in the k vs. e diagram.

The hydraulic conductivities are calculated following the Kozeny-Carman relations, which take into account the micro-arrangement of particles via a tortuosity calculation. The generation of 2D images shows that the preservation of the isotropic arrangement of particles is limited by a minimum porosity value. A decrease of the porosity value below this limit can be explained only by a progressive anisotropic rearrangement of the particles.

The microtexture behaviour, induced by the superimposition of the compaction, orientation and particle flattening and delamination stages, causes an anisotropy of the hydraulic conductivity which affects (1) the interstitial water flow direction, (2) the rotation of particles itself, and (3) the damage mechanism of the clay.
Hydrothermal transformations of kaolinite at 200 and 250°C in the systems Li2O–Na2O–MgO–Al2O3–SiO2–H2O–HCl and Li2O–K2O–MgO–Al2O3–SiO2–H2O–HCl
Authors: Bentabol M. , Ruiz Cruz M.D. , Huertas F.J. , Linares J.
Published: October 2004

The hydrothermal reaction of kaolinite in the systems Li2O–K2O–MgO–Al2O3–SiO2–H2O–HCl and Li2O–Na2O–MgO–Al2O3–SiO2–H2O–HCl, at pH between 9 and 11, has been investigated at 200–250°C from 1 to 180 days.The X-ray diffraction study of the K-bearing system indicates that the solid products formed were Li-A(BW) zeolite, crystalline silica, and randomly ordered chlorite-smectite mixed layers, dioctahedral on average, with a chlorite:smectite ratio of ~1:4.Study by electron microscopy reveals, however, the presence of mixtures of very thin particles of smectite, di,trioctahedral chlorite and mixed-layer phases.The X-ray study of the solid products formed in the Na-bearing system reveals that the neo-formed phases were Li-A(BW) zeolite, analcime and partially ordered chlorite-vermiculite mixed-layers with high chlorite:vermiculite ratio. The transmission microscopic study of these phases shows the presence of dioctahedral ‘vermiculitic’ curved particles and di,trioctahedral chlorite-like particles.In both cases, long reaction times cause formation of a 7 Å phase with composition intermediate between kaolinite and serpentine.The composition of the solutions suggests that the stable phases would be chlorite/smectite mixed-layers, with compositions near tosudite in the case of the K-bearing reaction and both a dioctahedral phase (tosudite?) and a trioctahedral one (clinochlore) in the case of the Na-bearing reaction.
Transforming property of TEL-FGFR3 mediated through PI3-K in a T-cell lymphoma that subsequently progressed to AML
Authors: Maeda Tomoya , Yagasaki Fumiharu , Ishikawa Maho , Takahashi Naoki , Bessho Masami
Published: October 2004

We previously reported a novel fusion between TEL and FGFR3 in a patient with peripheral T-cell lymphoma with t(4; 12)(p16;p13). Disease in this patient subsequently progressed to acute myelogenous leukemia (AML) with the same translocation. Sequence analysis of TEL-FGFR3 fusion transcripts suggested that these diseases originated from the same multipotent stem cell. To determine the transforming property of TEL-FGFR3, we established transfectants of this chimeric fusion gene and investigated the major signal pathways of TEL-FGFR3–induced transformation using various signal transduction inhibitors including SU5402 (fibroblast growth factor tyrosine kinase [FGFR TK] inhibitor). Our results indicated that (1) the expression of TEL-FGFR3 but not ΔHLH-TEL-FGFR3 resulted in efficient focus formation in NIH/3T3 cells and conferred interleukin 3 independence to Ba/F3 cells by a constitutive tyrosine kinase activity probably through oligomerization by the HLH domain of TEL; (2) although effector proteins including classical mitogen-activated protein kinase (MAPK), p38 MAPK, phosphatidylinositol 3-kinase (PI3-K), mammalian target or rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT-3) and STAT-5 were activated in TEL-FGFR3 transformants, the growth of the transformants was inhibited by SU5402 (concentration that inhibits 50% [IC50] = 5 μM) and the PI3-K inhibitor, LY294002 (IC50 = 10 μM) and wortmannin (IC50 = 5 μM), but not by U0126, SB203580, or rapamycin; and (3) injection of TEL-FGFR3 transformants induced lethal leukemia into syngeneic mice. Taken together, the leukemogenic potential of TEL-FGFR3 may be mediated in part through PI3-K.
Increased frequency of detection ofChlamydophila pneumoniaein asthma
Authors: Biscione G.L. , Corne J. , Chauhan A.J. , Johnston S.L.
Published: October 2004

Previous studies have suggested that chronicChlamydophila pneumoniaeinfection may play a role in the pathogenesis of asthma. However, most studies have been based on serology and have been unable to differentiate acute from chronic infection.

The present authors assessed the presence of acute and chronicC. pneumoniaeinfection in 74 spouse pairs, each consisting of one atopic asthmatic and one nonatopic nonasthmatic. Nasal secretions were sampled every 2 weeks from October to December and actively replicatingC. pneumoniaeinfection was detected by specific RT-PCR.

C. pneumoniaewas detected in 31 out of 709 samples analysed, 23 (6.4%) were positive in 362 samples from asthmatic participants and in eight out of 347 (2.3%) samples from their normal spouses (with a significant difference in infection rates, 95% confidence interval: 4.2%, 1.2–7.2%). A total of 16 (22%) asthmatic and seven (9%) normal participants were positive at least once during the study.

These data confirm thatChlamydophila pneumoniaeinfection is detected more frequently among asthmatic participants than normal control participants. Further studies are required to confirm whether infections are also present in the lower airway and whetherChlamydophila pneumoniaeinfection plays a role in disease pathogenesis.
Always Having to Say You’re Sorry: an ethical response to making mistakes in professional practice
Authors: Crigger Nancy J
Published: October 2004

Efforts to decrease errors in health care are directed at prevention rather than at managing a situation when a mistake has occurred. Consequently, nurses and other health care providers may not know how to respond properly and may lack sufficient support to make a healthy recovery from the mental anguish and emotional suffering that often accompany making mistakes. This article explores the conceptualization of mistakes and the ethical response to making a mistake. There are three parts to an ethical response to error: disclosure, apology and amends. Honesty and humility are discussed as important virtues that facilitate coping and personal growth for the health care provider who is involved in mistakes. In conclusion, a healthy view of nursing practice and mistake making is one that prevents error but, when prevention is not possible, accepts fallibility as part of the human condition and achieves the best possible outcome for all.
Humility and its Practice in Nursing
Authors: de Vries Kay
Published: October 2004

Following a personal experience of transformation as a result of washing the feet of a terminally ill patient, an exploratory study was undertaken to investigate nurses’ experience of washing patients’ feet. Seven postregistration student nurses participated in the study by washing the feet of as many patients as they could over a defined period of time. They were then interviewed about the experience. The transcribed interviews were analysed using the heuristic enquiry approach. Symbolically, washing feet is an act of humility. In washing feet in the manner required for this study I suggest that the nurses were practising beyond role definition of duty of care. As a result of this they experienced interconnectedness and changes in their relationship with the patients whose feet they had washed that could be interpreted as a response to humility.
Emerging Health Sector Problems Affecting Patient Rights in Turkey
Authors: Büken Nüket Örnek , Büken Erhan
Published: October 2004

It is accepted throughout the world today that a new approach is needed to health care, one that brings to the forefront the role of economic development. This situation has also increased the importance of the health care sector and health data have begun to take a significant place in countries’ development indicators. Health care services as a basic indicator of social and economic development in Turkey, as in the rest of the world, continue to gain in importance. However, there is a significant difference between health indicators for Turkey, which is a candidate for full membership of the European Union, and European Union countries.
Psychopathic personality in young people
Authors: Dolan Mairead
Published: October 2004

This article is an overview of developments in psychopathy and their application to children and adolescents. A key question is whether or not psychopathy is stable throughout the lifespan. Some characteristics indicate phenotypic similarities with adult psychopathy, and current instruments appear to be measuring similar constructs across the age ranges. Although the literature on developmental aspects of psychopathy in young people is limited, a number of instruments have been designed to measure the construct. These tools appear to have reasonable construct, concurrent and predictive validity, but we cannot yet recommend their routine use in clinical practice or in the criminal justice system, given the limited evidence base on their predictive validity. At best, they should be viewed as a means of subtyping potentially high-risk groups with a view to treatment planning.
Trends in service use and treatment for mental disorders in adults throughout Great Britain
Authors: Brugha Traolach S. , Bebbington Paul E. , Singleton Nicola , Melzer David , Jenkins Rachel , Lewis Glyn , Farrell Michael , Bhugra Dinesh , Lee Alison , Meltzer Howard
Published: October 2004

Background

Trends in health treatments and outcomes in the general population may be used to monitor achievement of health targets.

Aims

To investigate changes in mental health services and treatment in Britain over a 7-year period.

Method

National surveys of psychiatric morbidity were completed in 1993 and 2000 in households throughout Great Britain. Standardised interviews were used to establish psychiatric case status and service and treatment utilisation in adults aged 16–64 years.

Results

Use of psychotropic medication doubled in those designated as psychiatric cases. In the non-case-status population antidepressant use rose from 0.16% in 1993 (95% Cl 0.07–0.25) to 2.02% in 2000 (95% Cl 1.69–2.35). However, the overall prevalence of neurotic and psychotic disorder hardly changed from 1993 to 2000. Use of specialised ‘talking treatments' did not increase significantly, except in the non-case group.

Conclusions

Treatment with psychotropic medication alone is unlikely to improve the overall mental health of the nation. A policy based almost exclusively on treatment of identified cases should be augmented by preventive approaches.
Service innovation in a heated environment: CATS on a hot tin roof
Authors: Ingram Graham , Tacchi Mary Jane
Published: October 2004

Over the past few years, numerous articles have highlighted the strain on (and drain of staff from) our specialty. Many general adult psychiatrists are developing bleak views of themselves, the world and the future. Encouragingly, consultants such as Hampson (2003) are structuring their roles with some success. However, we are going through a major overhaul of the model of delivery of care and need to adapt our roles accordingly. Although tuning a Triumph Spitfire might make it run more smoothly for a while, it is still an inferior beast compared with a modern car and might be better on the scrap heap. A more radical approach is needed, which we outline in this article. One of the authors (G.I.) has experience of working as a consultant psychiatrist in Australia, where the state of Victoria changed the model of delivery of general adult psychiatric services to adopt a superior American model, leading to improved patient and carer satisfaction (Joyet al, 2001). The same model has been adopted by the UK government (Department of Health, 2001) through the creation of crisis assessment and treatment services (CATS), assertive outreach teams, and specialist community and in-patient services. Consultant psychiatrists are challenged to adapt their practice accordingly. The Royal College of Psychiatrists has recently set up a Working Group to address this issue (Royal College of Psychiatrists, 2004).
Randomized Multicenter Phase II Trial of a Biweekly Regimen of Fluorouracil and Leucovorin (LV5FU2), LV5FU2 Plus Cisplatin, or LV5FU2 Plus Irinotecan in Patients With Previously Untreated Metastatic Gastric Cancer: A Fédération Francophone de Cancérologie Digestive Group Study—FFCD 9803
Authors: Bouché Olivier , Raoul Jean Luc , Bonnetain Franck , Giovannini Marc , Etienne Pierre Luc , Lledo Gérard , Arsène Dominique , Paitel Jean Francois , Guérin-Meyer Véronique , Mitry Emmanuel , Buecher Bruno , Kaminsky Marie Christine , Seitz Jean François , Rougier Philippe , Bedenne Laurent , Milan Chantal
Published: October 2004

Purpose

To determine the efficacy and safety of a biweekly regimen of leucovorin (LV) plus fluorouracil (FU) alone or in combination with cisplatin or irinotecan in patients with previously untreated metastatic gastric adenocarcinoma and to select the best arm for a phase III study.

Patients and Methods

One hundred thirty-six patients (two were ineligible) were enrolled onto the randomized multicenter phase II trial. Patients received LV 200 mg/m2 (2-hour infusion) followed by FU 400 mg/m2 (bolus) and FU 600 mg/m2 (22-hour continuous infusion) on days 1 and 2 every 14 days (LV5FU2; arm A), LV5FU2 plus cisplatin 50 mg/m2 (1-hour infusion) on day 1 or 2 (arm B), or LV5FU2 plus irinotecan 180 mg/m2 (2-hour infusion) on day 1 (arm C).

Results

The overall response rates, which were confirmed by an independent expert panel, were 13% (95% CI, 3.4% to 23.3%), 27% (95% CI, 14.1% to 40.4%), and 40% (95% CI, 25.7% to 54.3%) for arms A, B, and C, respectively. Median progression-free survival and overall survival times were 3.2 months (95% CI, 1.8 to 4.6 months) and 6.8 months (95% CI, 2.6 to 11.1 months) with LV5FU2, respectively; 4.9 months (95% CI, 3.5 to 6.3 months) and 9.5 months (95% CI, 6.9 to 12.2 months) with LV5FU2-cisplatin, respectively; and 6.9 months (95% CI, 5.5 to 8.3 months) and 11.3 months (95% CI, 9.3 to 13.3 months) with LV5FU2-irinotecan, respectively.

Conclusion

Of the three regimens tested, the combination of LV5FU2-irinotecan is the most promising and will be assessed in a phase III trial.
Impact of Ulceration in Stages I to III Cutaneous Melanoma As Staged by the American Joint Committee on Cancer Staging System: An Analysis of the German Central Malignant Melanoma Registry
Authors: Eigentler Thomas K. , Buettner Petra G. , Leiter Ulrike , Garbe Claus
Published: October 2004

Purpose

In 2001, the new American Joint Committee on Cancer classification of cutaneous melanoma (CM) introduced ulceration of the primary melanoma as a new key parameter being represented in respective subcategories of the tumor (T) classification. The present study was performed to validate the prognostic significance of ulceration in relation to T thickness and clinical stages of CM (stages I to III).

Patients and Methods

Patients (N = 15,158) with incident invasive primary nonmetastatic CM and follow-up data recorded between 1976 and 2000 by the German Central Malignant Melanoma Registry were investigated using survival analysis to evaluate prognostic factors such as T thickness, level of invasion, body site, histologic subtype, ulceration, regression, age, and sex.

Results

Comparisons of survival probabilities according to the Kaplan-Meier method between ulcerated and nonulcerated CM were not statistically significant for subgroups with T thickness ≤ 1 mm and more than 4.00 mm (P = .2601 and P = .0699, respectively) but were significant for T thickness of 1.01 to 2.00 mm and 2.01 to 4.00 mm (P < .0001 for both). This result was confirmed in the multivariate analysis. For stage III CM, the impact of ulceration on overall survival was statistically significant in the bivariate Cox model (P = .0111) but not in the multivariate Cox model (P = .0522).

Conclusion

Whereas ulceration seems to have a negative impact on the prognosis of patients with stages T2 and T3, a potential influence for patients with stages T1 and T4 could not be established. If factors of the primary CM were to be taken into consideration to judge prognosis of stage III CM, T thickness but not ulceration should be the focus.
Phase I and Pharmacokinetic Study of Thalidomide With Carboplatin in Children With Cancer
Authors: Chintagumpala Murali , Blaney Susan M. , Bomgaars Lisa R. , Aleksic Aleksander , Kuttesch John F. , Klenke Renee A. , Berg Stacey L.
Published: October 2004

Purpose

Tumor growth and metastasis is believed to depend on the tumor's ability to induce neovascularization. Recent studies have indicated that thalidomide inhibits angiogenesis. We performed a phase I and pharmacokinetic study of thalidomide with carboplatin in children with refractory solid tumors.

Patients and Methods

Carboplatin was administered as a single intravenous dose once every 21 days at a target area under the concentration-time curve of 6 mg/mL·min. Thalidomide was administered daily by mouth. The initial dose level was 100 mg/m2/d with intrapatient dose escalation to a maximum dose of 300 mg/m2/d. The next cohort of patients started at a dose of 300 mg/m2/d, with intrapatient dose escalation to a maximum dose of 500 mg/m2/d. Standard response and adverse event criteria were used. Serial blood samples for thalidomide pharmacokinetics studies were obtained after the first dose.

Results

Twenty-two patients received 56 cycles of therapy. The maximum tolerated thalidomide dose was 400 mg/m2/d. The dose-limiting toxicity was somnolence. There were no objective responses. Thalidomide's apparent clearance was 55 ± 16 mL/min/m2 and the terminal half-life was 5.9 ± 2.8 hours. There was no evidence of dose-dependent pharmacokinetics in the narrow range studied.

Conclusion

Thalidomide at a dose of 400 mg/m2/d can be safely administered to children with solid tumors in combination with carboplatin. Somnolence is the major toxicity. In addition, we have characterized the pharmacokinetic behavior of thalidomide in children. This study can serve as the basis for future investigation of thalidomide as an anticancer agent in children.
Accuracy of Whole-Body Dual-Modality Fluorine-18–2-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography and Computed Tomography (FDG-PET/CT) for Tumor Staging in Solid Tumors: Comparison With CT and PET
Authors: Antoch Gerald , Saoudi Nina , Kuehl Hilmar , Dahmen Gerlinde , Mueller Stefan P. , Beyer Thomas , Bockisch Andreas , Debatin Jörg F. , Freudenberg Lutz S.
Published: October 2004

Purpose

To assess the accuracy of positron emission tomography/computed tomography (PET/CT) when staging different malignant diseases.

Patients and Methods

This was a retrospective, blinded, investigator-initiated study of 260 patients with various oncological diseases who underwent fluorine-18–2-fluoro-2-deoxy-d-glucose PET/CT for tumor staging. CT images alone, PET images alone, PET + CT data viewed side by side, and fused PET/CT images were evaluated separately according to the tumor-node-metastasis system. One hundred forty patients with tumors not staged according to the tumor-node-metastasis system or a lack of reference standard were excluded from data analysis; 260 patients were included. Diagnostic accuracies were determined for each of the four image sets. Histopathology and a clinical follow-up of 311 (± 125) days served as standards of reference.

Results

PET/CT proved significantly more accurate in assessing tumor-node-metastasis system stage compared with CT alone, PET alone, and side-by-side PET + CT (P < .0001). Of 260 patients, 218 (84%; 95% CI, 79% to 88%) were correctly staged with PET/CT, 197 (76%; 95% CI, 70% to 81%) with side-by-side PET + CT, 163 (63%; 95% CI, 57% to 69%) with CT alone, and 166 (64%; 95% CI, 58% to 70%) with PET alone. Combined PET/CT had an impact on the treatment plan in 16, 39, and 43 patients when compared with PET + CT, CT alone, and PET alone, respectively.

Conclusion

Tumor staging with PET/CT is significantly more accurate than CT alone, PET alone, and side-by-side PET + CT. This diagnostic advantage translates into treatment plan changes in a substantial number of patients.
Role of Lung Transplantation in the Treatment of Bronchogenic Carcinomas for Patients With End-Stage Pulmonary Disease
Authors: de Perrot Marc , Chernenko Susan , Waddell Thomas K. , Shargall Yaron , Pierre Andrew F. , Hutcheon Michael , Keshavjee Shaf
Published: October 2004

Purpose

To determine the role of lung transplantation in the treatment of patients presenting with bronchogenic carcinoma and end-stage lung disease.

Methods

An international survey was conducted to determine the outcome of patients with bronchogenic carcinoma in the explanted lung at the time of transplantation. A group of 69 patients was collected from 33 centers.

Results

Twenty-six patients underwent 29 lung transplantations for advanced multifocal bronchioloalveolar carcinoma (BAC) as the primary indication for transplantation, and 13 developed a recurrence, with an overall 5-year actuarial survival of 39%. Incidental bronchogenic carcinomas classified as stage I (n = 22), II (n = 12), and III (n = 2), or as incidental multifocal BAC (n = 7), were found in the explanted lung of the remaining 43 patients. The 5-year actuarial survival was 51% in patients with stage I carcinomas, and was significantly better than for patients with stage II and III carcinomas (survival of 14%) or with incidental multifocal BAC (survival of 23%). Time from transplantation to recurrence and from recurrence to death was significantly longer in patients with multifocal BAC than in patients with other types of bronchogenic carcinoma. In addition, the site of recurrence was limited to the transplanted lung in 88% of the patients with multifocal BAC, whereas it was always widespread in patients with other types of bronchogenic carcinoma.

Conclusion

This study demonstrates that long-term survival can be achieved after lung transplantation in patients with stage I bronchogenic carcinoma or with advanced multifocal BAC.
Infants' Evolving Representations of Object Motion During Occlusion: A Longitudinal Study of 6‐ to 12‐Month‐Old Infants
Authors: Gredebäck Gustaf , von Hofsten Claes
Published: October 2004

Infants' ability to track temporarily occluded objects that moved on circular trajectories was investigated in 20 infants using a longitudinal design. They were first seen at 6 months and then every 2nd month until the end of their 1st year. Infants were presented with occlusion events covering 20% of the target's trajectory (effective occlusion interval ranged from 500–4,000 msec). Gaze was measured using an ASL 504 infrared eye‐tracking system. Results effectively demonstrate that infants from 6 months of age can represent the spatiotemporal dynamics of occluded objects. Infants at all ages tested were able to predict, under certain conditions, when and where the object would reappear after occlusion. They moved gaze accurately to the position where the object was going to reappear and scaled their timing to the current occlusion duration. The average rate of predictive gaze crossings increased with occlusion duration. These results are discussed as a 2‐factor process. Successful predictions are dependent on strong representations, themselves dependent on the richness of information available during encoding and graded representations.
Anticipatory Eye Movements Reveal Infants' Auditory and Visual Categories
Authors: McMurray Bob , Aslin Richard N.
Published: October 2004

We introduce a new paradigm for the assessment of auditory and visual categories in 6‐month‐old infants using a 2‐alternative anticipatory eye‐movement response. Infants were trained by 2 different methods to anticipate the location of a visual reinforcer at 1 of 2 spatial locations (right or left) based on the identity of 2 cuing stimuli. After a training phase, infants were presented with a series of generalization trials in which novel (untrained) stimuli served as the cue to the anticipatory eye movement. Four experiments illustrated that infants can learn the 2‐choice discriminative response during training. Infants also showed anticipatory eye movements to novel stimuli, indicating sensitivity to variations along a variety of stimulus dimensions (e.g., color, shape, orientation, spatial frequency, pitch, and duration). In addition, the paradigm can be used to assess categorization in individual infants, thereby revealing the stimulus dimensions to which infants naturally attend.
Carane derivative stereoisomers of different local anaesthetic and antiplatelet activity similarly potentiate forskolin-stimulated cyclic AMP response and bind to β-adrenoceptors in the rat brain cortex
Authors: Librowski Tadeusz , Vetulani Jerzy , Nalepa Irena
Published: October 2004

A carane derivative, KP-23 [RS](–)-4-(2-hydroxy-3)N-isopropylamino)-propoxyimino)-cis-carane, was earlier described as a potential local anaesthetic and antiplatelet agent, and the following studies revealed that its R and S stereoisomers, KP-23R and KP-23S, have different potencies in the infiltration anaesthesia and platelet aggregation tests. The effects of these stereoisomers on the cyclic AMP (cAMP) generating system and the displacement of [3H]CGP 12177 (a β-adrenoceptor ligand) from its binding sites in the rat cerebral cortical tissue were investigated. The stereoisomers did not affect the basal cAMP level, but, at concentrations between 10−4 and 10−3m, they elevated the forskolin-induced accumulation of cAMP with similar potency. The compounds displaced [3H]CGP 12177, however the stereoisomer R was less potent than the racemic KP-23 and the S form (Ki = 64.1 ± 5.9 nm, 161.1 ± 10 nm and 62.1 ± 5.6 nm for KP-23, KP-23R and KP-23S, respectively). The fact that the stereoisomers differed in both tests only slightly, if at all, suggests that their pharmacological effects are not related to the action on the β-adrenoceptor/adenylate cyclase system.
Inhibition of Jagged-mediated Notch signaling disrupts zebrafish biliary development and generates multi-organ defects compatible with an Alagille syndrome phenocopy
Authors: Lorent Kristin , Yeo Sang-Yeob , Oda Takaya , Chandrasekharappa Settara , Chitnis Ajay , Matthews Randolph P. , Pack Michael
Published: October 2004

The Alagille Syndrome (AGS) is a heritable disorder affecting the liver and other organs. Causative dominant mutations in human Jagged 1 have been identified in most AGS patients. Related organ defects occur in mice that carry jagged 1 and notch 2 mutations. Multiple jagged and notch genes are expressed in the developing zebrafish liver. Compound jagged and notch gene knockdowns alter zebrafish biliary, kidney, pancreatic, cardiac and craniofacial development in a manner compatible with an AGS phenocopy. These data confirm an evolutionarily conserved role for Notch signaling in vertebrate liver development, and support the zebrafish as a model system for diseases of the human biliary system.
Delta proteins and MAGI proteins: an interaction of Notch ligands with intracellular scaffolding molecules and its significance for zebrafish development
Authors: Wright Gavin J. , Leslie Jonathan D. , Ariza-McNaughton Linda , Lewis Julian
Published: October 2004

Delta proteins activate Notch through a binding reaction that depends on their extracellular domains; but the intracellular (C-terminal) domains of the Deltas also have significant functions. All classes of vertebrates possess a subset of Delta proteins with a conserved ATEV* motif at their C termini. These ATEV Deltas include Delta1 and Delta4 in mammals and DeltaD and DeltaC in the zebrafish. We show that these Deltas associate with the membrane-associated scaffolding proteins MAGI1, MAGI2 and MAGI3, through a direct interaction between the C termini of the Deltas and a specific PDZ domain (PDZ4) of the MAGIs. In cultured cells and in subsets of cells in the intact zebrafish embryo, DeltaD and MAGI1 are co-localized at the plasma membrane. The interaction and the co-localization can be abolished by injection of a morpholino that blocks the mRNA splicing reaction that gives DeltaD its terminal valine, on which the interaction depends. Embryos treated in this way appear normal with respect to some known functions of DeltaD as a Notch ligand, including the control of somite segmentation, neurogenesis, and hypochord formation. They do, however, show an anomalous distribution of Rohon-Beard neurons in the dorsal neural tube, suggesting that the Delta-MAGI interaction may play some part in the control of neuron migration.
The geneFLORAL ORGAN NUMBER1regulates floral meristem size in rice and encodes a leucine-rich repeat receptor kinase orthologous toArabidopsisCLAVATA1
Authors: Suzaki Takuya , Sato Makoto , Ashikari Motoyuki , Miyoshi Masahiro , Nagato Yasuo , Hirano Hiro-Yuki
Published: October 2004

The regulation of floral organ number is closely associated with floral meristem size. Mutations in the gene FLORAL ORGAN NUMBER1(FON1) cause enlargement of the floral meristem in Oryza sativa (rice), resulting in an increase in the number of all floral organs. Ectopic floral organs develop in the whorl of each organ and/or in the additional whorls that form. Inner floral organs are more severely affected than outer floral organs. Many carpel primordia develop indeterminately, and undifferentiated meristematic tissues remain in the center in almost-mature flowers. Consistent with this result, OSH1, a molecular marker of meristematic indeterminate cells in rice, continues to be expressed in this region. Although floral meristems are strongly affected by the fon1-2mutation, vegetative and inflorescence meristems are largely normal, even in this strong allele. We isolated the FON1 gene by positional cloning and found that it encodes a leucine-rich repeat receptor-like kinase most similar to CLAVATA1 (CLV1) in Arabidopsis thaliana. This suggests that a pathway similar to the CLV signaling system that regulates meristem maintenance in Arabidopsis is conserved in the grass family. Unlike CLV1, which is predominantly expressed in the L3 layer of the shoot meristem, FON1 is expressed throughout the whole floral meristem,suggesting that small modifications to the CLV signaling pathway may be required to maintain the floral meristem in rice. In addition, FON1transcripts are detected in all meristems responsible for development of the aerial part of rice, suggesting that genes sharing functional redundancy with FON1 act in the vegetative and inflorescence meristems to mask the effects of the fon1 mutation.
Spalt transcription factors are required for R3/R4 specification and establishment of planar cell polarity in theDrosophilaeye
Authors: Domingos Pedro M. , Mlodzik Marek , Mendes César S. , Brown Samara , Steller Hermann , Mollereau Bertrand
Published: October 2004

The establishment of planar cell polarity in the Drosophila eye requires correct specification of the R3/R4 pair of photoreceptor cells. In response to a polarizing factor, Frizzled signaling specifies R3 and induces Delta, which activates Notch in the neighboring cell, specifying it as R4. Here, we show that the spalt zinc-finger transcription factors(spalt major and spalt-related) are part of the molecular mechanisms regulating R3/R4 specification and planar cell polarity establishment. In mosaic analysis, we find that the spalt genes are specifically required in R3 for the establishment of correct ommatidial polarity. In addition, we show that spalt genes are required for proper localization of Flamingo in the equatorial side of R3 and R4, and for the upregulation of Delta in R3. These requirements are very similar to those of frizzled during R3/R4 specification. We show that spalt genes are required cell-autonomously for the expression of seven-up in R3 and R4, and that seven-up is downstream of spalt genes in the genetic hierarchy of R3/R4 specification. Thus, spalt and seven-up are necessary for the correct interpretation of the Frizzled-mediated polarity signal in R3. Finally, we show that, posterior to row seven, seven-up represses spaltin R3/R4 in order to maintain the R3/R4 identity and to inhibit the transformation of these cells to the R7 cell fate.
Studies of Liquid-Phase Complexes in Acetonitrile/Water Solutions by Attenuated Total Reflection Infrared Spectroscopy with Acetaldehyde as a Model Solute
Authors: Fillipan Nathaniel , Bezemer Ernst , Burke Julie , Rutan Sarah C.
Published: October 2004

Chemometric methods combined with infrared (IR) spectroscopy, using attenuated total reflectance (ATR) sampling, are employed here to characterize the stoichiometry of complexes of solvent molecules in the liquid phase. The spectral information provides insight into the liquid microstructure present in liquid chromatographic mobile phases. This information should make it easier to understand and predict the effects of changes in mobile phase composition on the results of chromatographic separations. In this paper, mobile phases consisting of 0 mol % to 100 mol % acetonitrile in water were studied, with the addition of acetaldehyde as a model solute at concentrations ranging from 3 to 8 mol %. Using three-way multivariate curve resolution by the alternating least squares method (MCR-ALS) it was possible to resolve eight unique spectra: four mobile phase components, and four unique spectra of acetaldehyde solvated in different environments. The directions of the shifts of the important acetaldehyde infrared bands show good correlation with those predicted by gas-phase ab initio calculations of small solvated clusters.
Using the Linearization Approach for Synchronizing the Phase of Photoacoustic Reference and Sample Data
Authors: Pichler Arthur , Sowa Michael G.
Published: October 2004

Linearization of photoacoustic spectra is a technique that allows for detection of surface layers and the compensation of saturation effects in photoacoustic spectra by combining amplitude and phase information. The objective of this report is a thorough description of the linearization procedure. The influence of interferogram rotation on the real and imaginary parts of the complex Fourier transformation and on spectral phase angles is shown. The possibility of using the linearization approach to correct for phase differences between reference and sample data is discussed. The method can be used to calculate phase spectra from photoacoustic spectra taken with rapid scan spectrometers.