bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral acantholytic squamous cell carcinoma shares clinical and histological features with angiosarcoma
Authors: Driemel Oliver , Müller-Richter Urs DA , Hakim Samer G , Bauer Richard , Berndt Alexander , Kleinheinz Johannes , Reichert Torsten E , Kosmehl Hartwig
Published: July 2008

Background

acantholytic squamous cell carcinomas (ASCC) and intraoral angiosarcoma share similar histopathological features. Aim of this study was to find marker for a clear distinction.

Methods

Four oral acantholytic squamous cell carcinomas and one intraoral angiosarcoma are used to compare the eruptive intraoral growth-pattern, age-peak, unfavourable prognosis and slit-like intratumorous spaces in common histological staining as identical clinical and histopathological features. Immunohistochemical staining for pancytokeratin, cytokeratin, collagen type IV, γ2-chain of laminin-5, endothelial differentiation marker CD31 and CD34, F VIII-associated antigen, Ki 67-antigen, β-catenin, E-cadherin, α-smooth-muscle-actin and Fli-1 were done.

Results

Cytokeratin-immunoreactive cells can be identified in both lesions. The large vascularization of ASCC complicates the interpretation of vascular differential markers being characteristic for angiosarcoma. Loss of cell-cell-adhesion, monitored by loss of E-cadherin and β-catenin membrane-staining, are indetified as reasons for massive expression of invasion-factor ln-5 in ASCC and considered responsible for unfavourable prognosis of ASCC. Expression of Fli-1 in angiosarcoma and cellular immunoreaction for ln-5 in ASCC are worked out as distinguishing features of both entities.

Conclusion

Fli-1 in angiosarcoma and ln-5 in ASCC are distinguishing features.
Whole proteome identification of plant candidate G-protein coupled receptors in Arabidopsis, rice, and poplar: computational prediction and in-vivo protein coupling
Authors: Gookin Timothy E , Kim Junhyong , Assmann Sarah M
Published: July 2008

Background

The classic paradigm of heterotrimeric G-protein signaling describes a heptahelical, membrane-spanning G-protein coupled receptor that physically interacts with an intracellular Gα subunit of the G-protein heterotrimer to transduce signals. G-protein coupled receptors comprise the largest protein superfamily in metazoa and are physiologically important as they sense highly diverse stimuli and play key roles in human disease. The heterotrimeric G-protein signaling mechanism is conserved across metazoa, and also readily identifiable in plants, but the low sequence conservation of G-protein coupled receptors hampers the identification of novel ones. Using diverse computational methods, we performed whole-proteome analyses of the three dominant model plant species, the herbaceous dicot Arabidopsis thaliana (mouse-eared cress), the monocot Oryza sativa (rice), and the woody dicot Populus trichocarpa (poplar), to identify plant protein sequences most likely to be GPCRs.

Results

Our stringent bioinformatic pipeline allowed the high confidence identification of candidate G-protein coupled receptors within the Arabidopsis, Oryza, and Populus proteomes. We extended these computational results through actual wet-bench experiments where we tested over half of our highest ranking Arabidopsis candidate G-protein coupled receptors for the ability to physically couple with GPA1, the sole Gα in Arabidopsis. We found that seven out of eight tested candidate G-protein coupled receptors do in fact interact with GPA1. We show through G-protein coupled receptor classification and molecular evolutionary analyses that both individual G-protein coupled receptor candidates and candidate G-protein coupled receptor families are conserved across plant species and that, in some cases, this conservation extends to metazoans.

Conclusion

Our computational and wet-bench results provide the first step toward understanding the diversity, conservation, and functional roles of plant candidate G-protein coupled receptors.
Characterization and TCR variable region gene use of mouse resident nasal γδ T lymphocytes
Authors: Kim Chang-Hoon , Witherden Deborah A , Havran Wendy L
Published: July 2008

Tissue-resident γδ T lymphocytes, such as dendritic epidermal T cells, intestinal intraepithelial lymphocytes (IEL), and resident pulmonary lymphocytes, are known to support local tissue homeostasis and host defense. Inhaled antigens, toxins, and microorganisms first interact with the immune system through contact with the nasal mucosa. Herein, we characterized two populations of resident nasal lymphocytes (RNL) that are present in the nasal mucosa: nasal IEL (nIEL) and nasal lamina propria lymphocytes (nLPL). γδ TCR+ and αβ TCR+ nIEL and nLPL were detected by immunofluorescent staining. Mononuclear cells (5–15%) were CD3+ RNL by FACS analysis. Among the CD3+ RNL, 20–30% were GL3+ γδ T cells, which were double-negative for CD4 and CD8 and predominantly expressed a Vγ4/Vδ1 TCR. These results demonstrate that RNL might be crucial for the host defense and tissue homeostasis in the nasal mucosa.
Questionnaires for 360-degree assessment of consultant psychiatrists: Development and psychometric properties
Authors: Lelliott Paul , Williams Richard , Mears Alex , Andiappan Manoharan , Owen Helen , Reading Paul , Coyle Nick , Hunter Stephen
Published: July 2008

Background

Expert clinical judgement combines technical proficiency with humanistic qualities.

Aims

To test the psychometric properties of questionnaires to assess the humanistic qualities of working with colleagues and relating to patients using multisource feedback.

Method

Analysis of self-ratings by 347 consultant psychiatrists and ratings by 4422 colleagues and 6657 patients.

Results

Mean effectiveness as rated by self, colleagues and patients, was 4.6, 5.0 and 5.2 respectively (where 1=very low and 6=excellent). The instruments are internally consistent (Cronbach's alpha > 0.95). Principal components analysis of the colleague questionnaire yielded seven factors that explain 70.2% of the variance and accord with the domain structure. Colleague and patient ratings correlate with one another (r=0.39, P<0.001) but not with the self-rating. Ratings from 13 colleagues and 25 patients are required to achieve a generalisability coefficient (Eρ2) of 0.75.

Conclusions

Reliable 360-degree assessment of humane judgement is feasible for psychiatrists who work in large multiprofessional teams and who have large case-loads.
Effect of anxiety and depression on blood pressure: 11-year longitudinal population study
Authors: Hildrum Bjørn , Mykletun Arnstein , Holmen Jostein , Dahl Alv A.
Published: July 2008

Background

The long-term effect of anxiety and depression on blood pressure is unclear.

Aims

To examine the prospective association of anxiety and depression with change in blood pressure in a general population.

Method

Data on 36530 men and women aged 20–78 years participating in the Nord-Tr⊘ndelag Health Study (HUNT) in Norway in 1984–86 were re-examined 11 years later.

Results

A high symptom level of anxiety and depression at baseline predicted low systolic blood pressure (< 10th percentile) at follow-up (OR=1.30, 95% CI 1.08–1.57) when those with low systolic blood pressure at baseline were excluded. Change in symptom level of anxiety and depression between baseline and follow-up was inversely associated with change in systolic blood pressure. For diastolic blood pressure, the findings were weaker or non-significant.

Conclusions

Symptoms of anxiety and depression predicted lower blood pressure 11 years later.
Maintenance pharmacotherapy for recurrent major depressive disorder: 5-year follow-up study
Authors: Holma Irina A. K. , Holma K. Mikael , Melartin Tarja K. , Isometsä Erkki T.
Published: July 2008

Practice guidelines endorse maintenance antidepressant treatment for recurrent major depressive disorder. In the Vantaa Depression Study, we followed 218 psychiatric patients with major depressive disorder for up to 5 years with a life-chart. Of these patients, 86 (39.4%) had more than three lifetime episodes and an indication for maintenance pharmacotherapy. However, of these, only 57% received treatment and only for 16% of the time indicated. Good adherence to pharmacotherapy in the acute phase independently predicted maintenance treatment. The tertiary preventive impact of maintenance treatment may remain limited, as many patients with major depressive disorder either do not receive it, or receive it for too short a period.
Homicide due to mental disorder in England and Wales over 50 years
Authors: Large Matthew , Smith Glen , Swinson Nicola , Shaw Jenny , Nielssen Olav
Published: July 2008

Background

It has been stated that rates of homicide due to mental disorder are constant over time.

Aims

To examine whether there were changes in the rates of homicide due to mental disorder over time, and whether changes in these rates were associated with changes in the rates of other homicides in England and Wales.

Method

Examination of four sets of official homicide statistics from England and Wales from 1946 to 2004.

Results

The rate of total homicide and the rate of homicide due to mental disorder rose steadily until the mid-1970s. From then there was a reversal in the rate of homicides attributed to mental disorder, which declined to historically low levels, while other homicides continued to rise.

Conclusions

The reasons for the rise and fall in homicides attributed to mental disorder are not clear. The earlier increase in such homicides may have been due to the same sociological factors that caused the increase in other homicides over that time. The subsequent decline may have been due to improvements in psychiatric treatments and service organisation. Another possibility is that there has been an informal change to the legal tests for the finding of homicide due to mental disorder.
Community treatment orders are not a good thing
Authors: Lawton-Smith Simon , Dawson John , Burns Tom
Published: July 2008

Does politicians' enthusiasm for community treatment orders lie primarily in the area of public protection? If so, can such orders reduce homicide rates? Is there adequate evidence of their value, given their adverse effects on individual liberty? This well-researched and provocative debate will enlighten readers on these and many more of the complicated questions surrounding this issue.
Non-financial conflicts of interests in psychiatric research and practice
Authors: Maj Mario
Published: July 2008

Not all conflicts of interests affecting psychiatry are financial in nature. Our field is vulnerable to some varieties of non-financial conflicts of interests. Examples include the possible conflict between a researcher's allegiance to a school of thought and the integrity of psychotherapy research, or between a psychiatrist's political commitment and patient welfare.
Ethnicity and quality of antipsychotic prescribing among in-patients in south London
Authors: Connolly Anne , Taylor David
Published: July 2008

Ethnicity may influence treatment decisions in mental disorders. We undertook a survey of the prescribing of antipsychotics for in-patients in three south London mental health trusts. A total of 255 patients (152 White, 103 Black) were included. Median dose of antipsychotic (% of licensed dose) was 58.3% for White and 50.0% for Black patients (adjusted effect size=0.14, 95% CI −0.34 to 0.63). High-dose antipsychotics were prescribed to 15.1% of White and 11.7% of Black patients (adjusted odds ratio (OR)=0.5, 95% CI 0.19–1.33), and antipsychotic polypharmacy was recorded for 25.7% and 31.1% respectively (adjusted OR=3.05, 95% CI 1.44–6.46). Prescribing quality was similar for Black and White patients.
Bringing psychiatry training to the next generation: a Foundation Year 1 doctor's tale
Authors: Thomas Gareth , Knapp John
Published: July 2008

The Foundation Programme is a 2-year programme in the UK which forms the bridge between medical school and specialist/general practice training. It provides trainees with a broad range of experiences enabling them to apply for specialty training at an earlier stage. J.K., consultant psychiatrist in old age psychiatry, tells us about the experiences of hosting a Foundation Year 1 (FY1) doctor for the first time and the first incumbent G.T. (FY1) adds his views.
Neuropsychiatry in the UK: national survey of existing service provision
Authors: Agrawal Niruj , Fleminger Simon , Ring Howard , Deb Shoumitro
Published: July 2008

Aims and Method

To elucidate and describe current neuropsychiatry service provision in the UK. A questionnaire was developed and posted to members of the Royal College of Psychiatrists who had expressed an interest in neuropsychiatry. the responses were tabulated and analysed using descriptive statistics and SPSS version 11.0 for Windows. the neuropsychiatry services provided, sources of referrals, setting of the services and funding streams are described.

Results

Out of 251 respondents, 70 reported providing a neuropsychiatry service, 21 having been principally appointed as neuropsychiatrists.

Clinical Implications

Neuropsychiatry services in the UK are currently based in a few regional centres, representing a patchy and inadequate service provision.
Neuropsychiatry in the UK: planning the service provision for the 21st century
Authors: Agrawal Niruj , Fleminger Simon , Ring Howard , Deb Shoumitro
Published: July 2008

Some believe that Cartesian dualism of mind and body in the 19th century and the rise of psychoanalysis by the turn of the 20th century was what led to the separation of neurology and psychiatry. More recently, conceptualisations of the mind/brain paradigm have helped rediscover the relationship between the mind and the brain, bringing renewed synergy between neurology and psychiatry (Cunninghamet al, 2006). However, division is still apparent in current service planning and provision in the UK for individuals whose presentation lies in the no-man's-land between these two historical domains.
What is it about dynamic psychotherapy?
Authors: Dracass Sarah E. , Tracey Taryn , Bhui Kamaldeep
Published: July 2008

The new Modernising Medical Careers agenda in the UK raises concerns about maintaining the standard of psychotherapy training (Mizen, 2007). In 1993 the Royal College of Psychiatrists made psychotherapy a mandatory rather than recommended work experience and there is now a competency portfolio outlining requirements for trainees. However, startling data have been revealed recently, showing that 91% of senior house officers did not meet the requirements of the Member of the Royal College of Psychiatrists (MRCPsych) exam regarding psychotherapy training and 23% were not even aware of them (Agarwal et al, 2007). the quality and variability of psychotherapy experience in training have been surveyed in several papers (Podlesjka & Stern 2003; Carley & Mitchison 2006; Pretorius & Goldbeck 2006), and some solutions to practical problems with its provision have been proposed, for example, consultation from a consultant psychotherapist, utilising feedback from trainees, and focusing on practicalities and logistics at a local level (Wildgoose et al, 2002; Mitchison 2007). However, little has been said about trainees' own experiences of undertaking supervised practice in psychodynamic psychotherapy. This paper discusses trainees' outlook on psychotherapy training schemes.
Brian Lake: Formerly Consultant Psychotherapist, Leeds
Authors: Mindham R. H. S. , Sims A. C. P.
Published: July 2008

Brian was born in 1922 into a religious family who lived near Liverpool where his father was a jobber at the Liverpool Stock Exchange. He was the youngest of three brothers of whom the eldest, Frank, like Brian, studied medicine with a view to becoming a missionary in India. Brian began his studies in Edinburgh in 1940 and qualified with the ‘Scottish Triple’ in 1945. After house jobs at the Edinburgh Royal Infirmary and a period as Senior R.M.O. at the Royal Liverpool Children's Hospital. He was rejected for military service on medical grounds, so he decided to go to sea; he served with the Cunard White Star Line for the greater part of the 1950s. However, it was his contact with the crew and his involvement in negotiations to settle conflicts between them which most interested him and led to him to develop an interest in psychiatry. In the late 1950s he joined the junior staff at Warlingham Park Hospital in Surrey where he found himself among a stimulating group of trainees, many of whom later became distinguished in the psychiatric world. He obtained the DPM in 1961.
Combination Targeted Therapy With Sorafenib and Bevacizumab Results in Enhanced Toxicity and Antitumor Activity
Authors: Azad Nilofer S. , Posadas Edwin M. , Kwitkowski Virginia E. , Steinberg Seth M. , Jain Lokesh , Annunziata Christina M. , Minasian Lori , Sarosy Gisele , Kotz Herbert L. , Premkumar Ahalya , Cao Liang , McNally Deborah , Chow Catherine , Chen Helen X. , Wright John J. , Figg William D. , Kohn Elise C.
Published: July 2008

Purpose

Sorafenib inhibits Raf kinase and vascular endothelial growth factor (VEGF) receptor. Bevacizumab is a monoclonal antibody targeted against VEGF. We hypothesized that the complementary inhibition of VEGF signaling would have synergistic therapeutic effects.

Patients and Methods

Patients had advanced solid tumors, Eastern Cooperative Oncology Group performance status of 0 to 1, and good end-organ function. A phase I dose-escalation trial of sorafenib and bevacizumab was initiated at below-recommended single-agent doses because of possible overlapping toxicity: sorafenib 200 mg orally twice daily and bevacizumab intravenously at 5 mg/kg (dose level [DL] 1) or 10 mg/kg (DL2) every 2 weeks. Additional patients were enrolled at the maximum-tolerated dose (MTD).

Results

Thirty-nine patients were treated. DL1 was the MTD and administered in cohort 2 (N = 27). Dose-limiting toxicity in DL2 was grade 3 proteinuria and thrombocytopenia. Adverse events included hypertension, hand-foot syndrome, diarrhea, transaminitis, and fatigue. Partial responses (PRs) were seen in six (43%) of 13 patients with ovarian cancer (response duration range, 4 to 22+ months) and one of three patients with renal cell cancer (response duration, 14 months). PR or disease stabilization ≥ 4 months (median, 6 months; range, 4 to 22+ months) was seen in 22 (59%) of 37 assessable patients. The majority (74%) required sorafenib dose reduction to 200 mg/d at a median of four cycles (range, one to 12 cycles).

Conclusion

Combination therapy with sorafenib and bevacizumab has promising clinical activity, especially in patients with ovarian cancer. The rapidity and frequency of sorafenib dose reductions indicates that sorafenib at 200 mg twice daily with bevacizumab 5 mg/kg every 2 weeks may not be tolerable long term, and alternate sorafenib dosing schedules should be explored.
Variations in Quality of Care for Men With Early-Stage Prostate Cancer
Authors: Spencer Benjamin A. , Miller David C. , Litwin Mark S. , Ritchey Jamie D. , Stewart Andrew K. , Dunn Rodney L. , Gay E. Greer , Sandler Howard M. , Wei John T.
Published: July 2008

Purpose

The commencement of quality-improvement initiatives such as Pay for Performance and the Physician Consortium for Performance Improvement has underscored calls to evaluate the quality of cancer care on a patient level for nationally representative samples.

Methods

We sampled early-stage prostate cancer cases diagnosed in 2000 through 2001 from the American College of Surgeons National Cancer Data Base and explicitly reviewed medical records from 2,775 men (weighted total = 55,160 cases) treated with radical prostatectomy or external-beam radiation therapy. We determined compliance with 29 quality-of-care disease-specific structure and process indicators developed by RAND, stratified by race, geographic region, and hospital type.

Results

Overall compliance exceeded 70% for structural and pretherapy disease assessment indicators but was lower for documentation of pretreatment functioning (46.4% to 78.4%), surgical pathology (37.1% to 86.3%), radiation technique (62.6% to 88.3%), and follow-up (55%). Geographic variations were observed as higher compliance in the South Atlantic division than the New England division for having at least one board-certified urologist (odds ratio [OR], 9.2; 95% CI, 1.9 to 45.0), at least one board-certified radiation oncologist (OR, 3.3; 95% CI, 1.2 to 9.0), use of Gleason grading (OR, 4.1; 95% CI, 1.2 to 13.8), and administering total radiation dose ≥ 70 Gy (OR, 3.1; 95% CI, 1.6 to 6.1). Teaching/research hospitals and Comprehensive Cancer Centers had higher compliance than Community Cancer Centers, whereas racial differences were not observed for any indicator.

Conclusion

The significant and unwarranted variations observed for these quality indicators by census division and hospital type illustrate the inconsistencies in prostate cancer care and represent potential targets for quality improvement. The lack of racial disparities suggests equity in care once a patient initiates treatment.
Amifostine Protects Against Cisplatin-Induced Ototoxicity in Children With Average-Risk Medulloblastoma
Authors: Fouladi Maryam , Chintagumpala Murali , Ashley David , Kellie Stewart , Gururangan Sridharan , Hassall Tim , Gronewold Lindsey , Stewart Clinton F. , Wallace Dana , Broniscer Alberto , Hale Gregory A. , Kasow Kimberly A. , Merchant Thomas E. , Morris Brannon , Krasin Matthew , Kun Larry E. , Boyett James M. , Gajjar Amar
Published: July 2008

Purpose

To determine the role of amifostine as a protectant against cisplatin-induced ototoxicity in patients with average-risk (AR) medulloblastoma treated with craniospinal radiotherapy and four cycles of cisplatin-based, dose-intense chemotherapy and stem-cell rescue.

Patients and Methods

The primary objective was to determine whether, in patients with AR medulloblastoma (n = 62), amifostine would decrease the need for hearing aids (defined as ≥ grade 3 ototoxicity in one ear) compared with a control group (n = 35), 1 year from initiating treatment. Ninety-seven patients received craniospinal irradiation (23.4 Gy) followed by 55.8 Gy to the primary tumor bed using three-dimensional conformal technique, and four cycles of high-dose cyclophosphamide (4,000 mg/m2/cycle), cisplatin (75 mg/m2/cycle), and vincristine (two 1.5 mg/m2 doses/cycle) and stem-cell rescue. When used, amifostine (600 mg/m2/dose) was administered as a bolus immediately before and 3 hours into the cisplatin infusion.

Results

The median age of the 97 patients was 8.7 years (range, 3.2 to 20.2 years). The study and control groups were similar in age and sex distribution. Amifostine was well-tolerated. One year after treatment initiation, 13 patients (37.1%) in the control group versus nine (14.5%; one-sided χ2 test P = .005) of the amifostine-treated patients had at least grade 3 ototoxicity, requiring hearing aid in at least one ear.

Conclusion

Amifostine administered before and during the cisplatin infusion can significantly reduce the risk of severe ototoxicity in patients with AR medulloblastoma receiving dose-intense chemotherapy.
Randomized Phase III Study Comparing Preoperative Radiotherapy With Chemoradiotherapy in Nonresectable Rectal Cancer
Authors: Brændengen Morten , Tveit Kjell M. , Berglund Åke , Birkemeyer Elke , Frykholm Gunilla , Påhlman Lars , Wiig Johan N. , Byström Per , Bujko Krzysztof , Glimelius Bengt
Published: July 2008

Purpose

Preoperative chemoradiotherapy is considered standard treatment for locally advanced rectal cancer, although the scientific evidence for the chemotherapy addition is limited. This trial investigated whether chemotherapy as part of a multidisciplinary treatment approach would improve downstaging, survival, and relapse rate.

Patients and Methods

The randomized study included 207 patients with locally nonresectable T4 primary rectal carcinoma or local recurrence from rectal carcinoma in the period 1996 to 2003. The patients received either chemotherapy (fluorouracil/leucovorin) administered concurrently with radiotherapy (50 Gy) and adjuvant for 16 weeks after surgery (CRT group, n = 98) or radiotherapy alone (50 Gy; RT group, n = 109).

Results

The two groups were well balanced according to pretreatment characteristics. An R0 resection was performed in 82 patients (84%) in the CRT group and in 74 patients (68%) in the RT group (P = .009). Pathologic complete response was seen in 16% and 7%, respectively. After an R0 + R1 resection, local recurrence was found in 5% and 7%, and distant metastases in 26% and 39%, respectively. Local control (82% v 67% at 5 years; log-rank P = .03), time to treatment failure (63% v 44%; P = .003), cancer-specific survival (72% v 55%; P = .02), and overall survival (66% v 53%; P = .09) all favored the CRT group. Grade 3 or 4 toxicity, mainly GI, was seen in 28 (29%) of 98 and six (6%) of 109, respectively (P = .001). There was no difference in late toxicity.

Conclusion

CRT improved local control, time to treatment failure, and cancer-specific survival compared with RT alone in patients with nonresectable rectal cancer. The treatments were well tolerated.
Is Hepatic Resection Justified After Chemotherapy in Patients With Colorectal Liver Metastases and Lymph Node Involvement?
Authors: Adam René , de Haas Robbert J. , Wicherts Dennis A. , Aloia Thomas A. , Delvart Valérie , Azoulay Daniel , Bismuth Henri , Castaing Denis
Published: July 2008

Purpose

For patients with colorectal liver metastases (CLM), regional lymph node (RLN) involvement is one of the worst prognostic factors. The objective of this study was to evaluate the ability of a multidisciplinary approach, including preoperative chemotherapy and hepatectomy, to improve patient outcomes.

Patients and Methods

Outcomes for a consecutively treated group of patients with CLM and simultaneous RLN involvement were compared with a cohort of patients without RLN involvement. Univariate and multivariate analysis of clinical variables was used to identify prognostic factors in this high-risk group.

Results

Of the 763 patients who underwent resection at our institution for CLM between 1992 and 2006, 47 patients (6%) were treated with hepatectomy and simultaneous lymphadenectomy. All patients had received preoperative chemotherapy. Five-year overall survival (OS) for patients with and without RLN involvement were 18% and 53%, respectively (P < .001). Five-year disease-free survival rates were 11% and 23%, respectively (P = .004). When diagnosed preoperatively, RLN involvement had an increased 5-year OS compared with intraoperative detection, although the difference was not significant (35% v 10%; P = .18). Location of metastatic RLN strongly influenced survival, with observed 5-year OS of 25% for pedicular, 0% for celiac, and 0% for para-aortic RLN (P = .001). At multivariate analysis, celiac RLN involvement and age ≥ 40 years were identified as independent poor prognostic factors.

Conclusion

Combined liver resection and pedicular lymphadenectomy is justified when RLN metastases respond to or are stabilized by preoperative chemotherapy, particularly in young patients. In contrast, this approach does not benefit patients with celiac and/or para-aortic RLN involvement, even when patients’ disease is responding to preoperative chemotherapy.
SM22α-targeted deletion of bone morphogenetic protein receptor 1A in mice impairs cardiac and vascular development, and influences organogenesis
Authors: El-Bizri Nesrine , Guignabert Christophe , Wang Lingli , Cheng Alexander , Stankunas Kryn , Chang Ching-Pin , Mishina Yuji , Rabinovitch Marlene
Published: July 2008

Expression of bone morphogenetic protein receptor 1A (BMPR1A) is attenuated in the lung vessels of patients with pulmonary arterial hypertension, but the functional impact of this abnormality is unknown. We ablated Bmpr1a in cardiomyocytes and vascular smooth muscle cells(VSMCs) by breeding mice possessing a loxP allele of Bmpr1a(Bmpr1aflox) expressing R26R with SM22α-Cre mice. SM22α-Cre;R26R;Bmpr1aflox/flox mice died soon after embryonic day 11 (E11) with massive vascular and pericardial hemorrhage and impaired brain development. At E10.5, SM22α-Cre;R26R;Bmpr1aflox/flox embryos showed thinning of the myocardium associated with reduced cell proliferation. These embryos also had severe dilatation of the aorta and large vessels with impaired investment of SMCs that was also related to reduced proliferation. SM22α-Cre;R26R;Bmpr1aflox/flox mice showed collapsed telencephalon in association with impaired clearing of brain microvessels in areas where reduced apoptosis was observed. Transcript and protein levels of matrix metalloproteinase (MMP) 2 and 9 were reduced in E9.5 and E10.5 SM22α-Cre;R26R;Bmpr1aflox/floxembryos, respectively. Knock-down of BMPR1A by RNA interference in human pulmonary artery SMCs reduced MMP2 and MMP9 activity, attenuated serum-induced proliferation, and impaired PDGF-BB-directed migration. RNA interference of MMP2 or MMP9 recapitulated these abnormalities, supporting a functional interaction between BMP signaling and MMP expression. In human brain microvascular pericytes, knock-down of BMPR1A reduced MMP2 activity and knock-down of either BMPR1Aor MMP2 caused resistance to apoptosis. Thus, loss of Bmpr1a, by decreasing MMP2 and/or MMP9 activity, can account for vascular dilatation and persistence of brain microvessels, leading to the impaired organogenesis documented in the brain.
RNA polymerase II-mediated transcription at active loci does not require histone H3S10 phosphorylation inDrosophila
Authors: Cai Weili , Bao Xiaomin , Deng Huai , Jin Ye , Girton Jack , Johansen Jørgen , Johansen Kristen M.
Published: July 2008

JIL-1 is the major kinase controlling the phosphorylation state of histone H3S10 at interphase in Drosophila. In this study, we used three different commercially available histone H3S10 phosphorylation antibodies, as well as an acid-free polytene chromosome squash protocol that preserves the antigenicity of the histone H3S10 phospho-epitope, to examine the role of histone H3S10 phosphorylation in transcription under both heat shock and non-heat shock conditions. We show that there is no redistribution or upregulation of JIL-1 or histone H3S10 phosphorylation at transcriptionally active puffs in such polytene squash preparations after heat shock treatment. Furthermore, we provide evidence that heat shock-induced puffs in JIL-1 null mutant backgrounds are strongly labeled by antibody to the elongating form of RNA polymerase II (Pol IIoser2), indicating that Pol IIoser2 is actively involved in heat shock-induced transcription in the absence of histone H3S10 phosphorylation. This is supported by the finding that there is no change in the levels of Pol IIoser2 in JIL-1 null mutant backgrounds compared with wild type. mRNA from the six genes that encode the major heat shock protein in Drosophila, Hsp70, is transcribed at robust levels in JIL-1null mutants, as directly demonstrated by qRT-PCR. Taken together, these data are inconsistent with the model that Pol II-dependent transcription at active loci requires JIL-1-mediated histone H3S10 phosphorylation, and instead support a model in which transcriptional defects in the absence of histone H3S10 phosphorylation are a result of structural alterations of chromatin.
A complex RNA motif defined by three discontinuous 5-nucleotide-long strands is essential for Flavivirus RNA replication
Authors: Song Byung-Hak , Yun Sang-Im , Choi Yu-Jeong , Kim Jeong-Min , Lee Chan-Hee , Lee Young-Min
Published: July 2008

Tertiary or higher-order RNA motifs that regulate replication of positive-strand RNA viruses are as yet poorly understood. Using Japanese encephalitis virus (JEV), we now show that a key element in JEV RNA replication is a complex RNA motif that includes a string of three discontinuous complementary sequences (TDCS). The TDCS consists of three 5-nt-long strands, the left (L) strand upstream of the translation initiator AUG adjacent to the 5′-end of the genome, and the middle (M) and right (R) strands corresponding to the base of the Flavivirus-conserved 3′ stem–loop structure near the 3′-end of the RNA. The three strands are arranged in an antiparallel configuration, with two sets of base-pairing interactions creating L-M and M-R duplexes. Disrupting either or both of these duplex regions of TDCS completely abolished RNA replication, whereas reconstructing both duplex regions, albeit with mutated sequences, fully restored RNA replication. Modeling of replication-competent genomes recovered from a large pool of pseudorevertants originating from six replication-incompetent TDCS mutants suggests that both duplex base-pairing potentials of TDCS are required for RNA replication. In all cases, acquisition of novel sequences within the 3′M-R duplex facilitated a long-range RNA–RNA interaction of its 3′M strand with either the authentic 5′L strand or its alternative (invariably located upstream of the 5′ initiator), thereby restoring replicability. We also found that a TDCS homolog is conserved in other flaviviruses. These data suggest that two duplex base-pairings defined by the TDCS play an essential regulatory role in a key step(s) of Flavivirus RNA replication.
The anatomical tibial axis
Authors: Cobb J. P. , Dixon H. , Dandachli W. , Iranpour F.
Published: July 2008

The rotational alignment of the tibia is an unresolved issue in knee replacement. A poor functional outcome may be due to malrotation of the tibial component. Our aim was to find a reliable method for positioning the tibial component in knee replacement.

CT scans of 19 knees were reconstructed in three dimensions and orientated vertically. An axial plane was identified 20 mm below the tibial spines. The centre of each tibial condyle was calculated from ten points taken round the condylar cortex. The tibial tubercle centre was also generated as the centre of the circle which best fitted eight points on the outside of the tubercle in an axial plane at the level of its most prominent point.

The derived points were identified by three observers with errors of 0.6 mm to 1 mm. The medial and lateral tibial centres were constant features (radius 24 mm (sd 3), and 22 mm (sd 3), respectively). An anatomical axis was created perpendicular to the line joining these two points. The tubercle centre was found to be 20 mm (sd 7) lateral to the centre of the medial tibial condyle. Compared with this axis, an axis perpendicular to the posterior condylar axis was internally rotated by 6° (sd 3). An axis based on the tibial tubercle and the tibial spines was also internally rotated by 5° (sd 10).

Alignment of the knee when based on this anatomical axis was more reliable than either the posterior surfaces or any axis involving the tubercle which was the least reliable landmark in the region.
Osteonecrosis of the femoral head following an electrical injury to the leg
Authors: Vanderstraeten L. , Binns M.
Published: July 2008

We report a case of osteonecrosis of the femoral head in a young man who is a carrier of the prothrombin gene mutation. We suggest that an electrical injury to his lower limb may have triggered intravascular thrombosis as a result of this mutation with subsequent osteonecrosis of the femoral head. No case of osteonecrosis of the femoral head secondary to a distant electrical injury has previously been reported.
Endoprosthetic replacement for primary tumours around the knee
Authors: Guo W. , Ji T. , Yang R. , Tang X. , Yang Y.
Published: July 2008

In developing countries locally-made low-cost prostheses are mainly used in limb-salvage surgery to alleviate the economic burden.

We retrospectively collected data on 104 patients treated by limb-salvage surgery between July 1997 and July 2005. We used a locally-designed and fabricated stainless-steel endoprosthesis in each case. Oncological and functional outcomes were evaluated at a mean follow-up of 47 months (12 to 118).

A total of 73 patients (70.2%) were free from disease, nine (8.7%) were alive with disease, 19 (18.2%) had died from their disease and three (2.9%) from unrelated causes. According to the Musculoskeletal Tumor Society scoring system, the mean functional score was 76.3% (SD 17.8). The five-year survival for the implant was 70.5%. There were nine cases (8.7%) of infection, seven early and two late, seven (6.7%) of breakage of the prosthesis, three (2.9%) of aseptic loosening and two (1.9%) of failure of the polyethylene bushing. Multivariate analysis showed that a proximal tibial prosthesis and a resection length of 14 cm or more were significant negative prognostic factors.

Our survival rates and Musculoskeletal Tumor Society functional scores are similar to those reported in the literature. Although longer follow-up is needed to confirm our results, we believe that a low-cost custom-made endoprosthesis is a cost-effective and reliable reconstructive option for limb salvage in developing countries.
Clinical and radiological evaluation of revision hip arthroplasty using the cement-in-cement technique
Authors: Goto K. , Kawanabe K. , Akiyama H. , Morimoto T. , Nakamura T.
Published: July 2008

We reviewed 44 consecutive revision hip replacements in 38 patients performed using the cement-in-cement technique. All were performed for acetabular loosening in the presence of a well-fixed femoral component. The mean follow-up was 5.1 years (2 to 10.1). Radiological analysis at final follow-up indicated no loosening of the femoral component, except for one case with a continuous radiolucent line in all zones and peri-prosthetic fracture which required further revision. Peri-operative complications included nine proximal femoral fractures (20.4%) and perforation of the proximal femur in one hip. In five hips wiring or fixation with a braided suture was undertaken but no additional augmentation was required. There was an improvement in the mean Japanese Orthopaedic Association score from 55.5 (28 to 81) pre-operatively to 77.8 (40 to 95) at final follow-up (p < 0.001). Revision using a cement-in-cement technique allows increased exposure for acetabular revision and is effective in the medium term. Further follow-up is required to assess the long-term results in the light of in vitro studies which have questioned the quality of the cement-in-cement bond.
A prospective trial comparing the Holland nail with the dynamic hip screw in the treatment of intertrochanteric fractures of the hip
Authors: Little N. J. , Verma V. , Fernando C. , Elliott D. S. , Khaleel A.
Published: July 2008

We compared the outcome of patients treated for an intertrochanteric fracture of the femoral neck with a locked, long intramedullary nail with those treated with a dynamic hip screw (DHS) in a prospective randomised study.

Each patient who presented with an extra-capsular hip fracture was randomised to operative stabilisation with either a long intramedullary Holland nail or a DHS. We treated 92 patients with a Holland nail and 98 with a DHS. Pre-operative variables included the Mini Mental test score, patient mobility, fracture pattern and American Society of Anesthesiologists grading. Peri-operative variables were anaesthetic time, operating time, radiation time and blood loss. Post-operative variables were time to mobilising with a frame, wound infection, time to discharge, time to fracture union, and mortality.

We found no significant difference in the pre-operative variables. The mean anaesthetic and operation times were shorter in the DHS group than in the Holland nail group (29.7 vs 40.4 minutes, p < 0.001; and 40.3 vs 54 minutes, p < 0.001, respectively). There was an increased mean blood loss within the DHS group versus the Holland nail group (160 ml vs 78 ml, respectively, p < 0.001). The mean time to mobilisation with a frame was shorter in the Holland nail group (DHS 4.3 days, Holland nail 3.6 days, p = 0.012). More patients needed a post-operative blood transfusion in the DHS group (23 vs seven, p = 0.003) and the mean radiation time was shorter in this group (DHS 0.9 minutes vs Holland nail 1.56 minutes, p < 0.001). The screw of the DHS cut out in two patients, one of whom underwent revision to a Holland nail. There were no revisions in the Holland nail group. All fractures in both groups were united when followed up after one year.

We conclude that the DHS can be implanted more quickly and with less exposure to radiation than the Holland nail. However, the resultant blood loss and need for transfusion is greater. The Holland nail allows patients to mobilise faster and to a greater extent. We have therefore adopted the Holland nail as our preferred method of treating intertrochanteric fractures of the hip.
Fracture healing in HIV-positive populations
Authors: Richardson J. , Hill A. M. , Johnston C. J. C. , McGregor A. , Norrish A. R. , Eastwood D. , Lavy C. B. D.
Published: July 2008

Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing.

The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-α) and appears to impair the blood supply of bone.

Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.
Patch technique for repair of a dural tear in microendoscopic spinal surgery
Authors: Shibayama M. , Mizutani J. , Takahashi I. , Nagao S. , Ohta H. , Otsuka T.
Published: July 2008

A dural tear is a common but troublesome complication of endoscopic spinal surgery. The limitations of space make repair difficult, and it is often necessary to proceed to an open operation to suture the dura in order to prevent leakage of cerebrospinal fluid. We describe a new patch technique in which a small piece of polyglactin 910 is fixed to the injured dura with fibrin glue. Three pieces are generally required to obtain a watertight closure after lavage with saline. We have applied this technique in seven cases. All recovered well with no adverse effects. MRI showed no sign of leakage of cerebrospinal fluid.
Testing the predictive utility of the STATIC‐99: A Bayes analysis
Authors: Beauregard Eric , Mieczkowski Tom
Published: July 2008

Purpose. This study applies a Bayes analysis to the probability of a particular STATIC‐99 score and its associated re‐offence probability with recidivating for a sexual offence. We examine this probability over three time frames: within 5 years; within 10 years; and within 15 years.

Methods. This study was conducted using the same data from Hanson and Thornton (1999). This dataset is constituted from four different samples: Institut Philippe Pinel (Canada) sample; Millbrook Recidivism Study (Canada) sample; Oak Ridge Division of the Penetanguishene Mental Health Center (Canada) sample; and Her Majesty's Prison Service (UK) sample. The final sample for which sufficient information was available to score the STATIC‐99 includes 1,086 sexual offenders. Bayes statistic has been used to analyse the data.

Results. Results are consistent with the STATIC‐99 as a useful assessment tool. The Bayes‐generated probabilities as well as odds ratios show a consistent increase in increased likelihood of re‐offence as the score value increases.

Conclusions. The Bayesian analysis of the STATIC‐99 shows that this method is very interesting in the context of risk assessment tools. This approach to risk assessment instruments may be more appropriate in the communication of analytic results as it can offer clinicians a combination of probabilities and likelihood ratios resulting a readily accessible profile of risk.
Eye-Tracking – Visuelle Blickrichtungserfassung im dreidimensionalen Raum (Eye-Tracking – Visual Gaze Estimation in 3D Space)
Authors: Al Nahlaoui Mohammad Yasser
Published: July 2008

Computer werden vielfach zu Präsentationszwecken eingesetzt. Dazu zählt beispielsweise die Präsentation der täglichen Nachrichten, die Analyse und Erstellung aufwendiger technischer Zeichnungen sowie der Einsatz in der medizinischen Therapie und Diagnostik. Zur Qualitätssteigerung ist es jedoch wichtig zu wissen, wie der Benutzer mit der angezeigten Information interagiert. So könnte bspw. das Zeitungslayout optimiert, die technische Zeichnung dem Ingenieur näher gebracht oder die Therapie adaptiv dem Patienten angepasst werden. Um dies zu erreichen, ist es notwendig, die Blickrichtung des Benutzers zu erfassen, wie es von dem hier vorgestellten Eye-Tracking-System gewährleistet wird. In diesem Beitrag sollen nach einer Erläuterung des Systemaufbaus das Funktionsprinzip anhand des Augenmodells vorgestellt und die einzelnen Berechnungsschritte aufgezeigt werden. Sowohl die Berechnung als solches als auch Messreihen zum Einfluss einzelner Parameter sollen in diesem Beitrag vorgestellt und diskutiert werden.
Grupo de acompanhamento de portadores de Esquizofrenia em uso de Clozapina e de seus familiares: percepção dos participantes
Authors: Durão Ana Maria Sertori , Souza Maria Conceição Bernardo de Mello e , Miasso Adriana Inocenti
Published: July 2008

Este estudo descreveu a visão do portador de Esquizofrenia e de seu familiar sobre o acompanhamento em grupo. A população constou de 11 pacientes que participam do grupo e 11 familiares que os acompanham com maior freqüência ao mesmo. Para coleta de dados foram utilizadas entrevistas. Estas foram gravadas e, posteriormente, transcritas na íntegra. Obteve-se que o grupo: constituiu espaço oportuno para conversar e ouvir sobre a doença, trocar experiências; proporcionou maior segurança e auto-estima para seus integrantes e melhora nos relacionamentos dos pacientes e, constituiu ajuda terapêutica para os familiares. Tais resultados apontam a necessidade de um novo olhar para o portador de transtorno mental, no sentido de buscar atitudes terapêuticas mais adequadas que atuem na produção de vida.
A instituição da liderança dos enfermeiros em questões de saúde
Authors: Christovam Barbara , Santos Iraci
Published: July 2008

O problema em questão nesta pesquisa foi o fato de os enfermeiros passarem a ocupar cargos de liderança administrativa dentro da Fundação Municipal de Saúde de Niterói (FMS). A Análise Institucional, tendência René Lourau, foi o método utilizado para analisar as relações estabelecidas por 10 enfermeiros gerentes de saúde. O "corpus teórico" foi construído pelo discurso oral dos agentes, através de entrevista guiada, delimitando-se três categorias: O Desafio de Ser Gerente, O Desafio de Ser Líder e o Desafio da Tomada de Decisão. Entre os conhecimentos construídos, ressaltam-se os DESAFIOS que o enfermeiro tem de enfrentar na gerência de saúde, que são: organizar o trabalho de outros profissionais e assumir de fato o papel de líder no sistema de saúde.