bluuebunny/crossref_metadata_2025 huggingface dataset:
Titanocene / cyclodextrin supramolecular systems: a theoretical approach
Authors: Riviş Adrian , Hădărugă Nicoleta G , Gârban Zeno , Hădărugă Daniel I
Published: November 2012

Background

Recently, various metallocenes were synthesized and analyzed by biological activity point of view (such as antiproliferative properties): ruthenocenes, cobaltoceniums, titanocenes, zirconocenes, vanadocenes, niobocenes, molibdocenes etc. Two main disadvantages of metallocenes are the poor hydrosolubility and the hydrolytic instability. These problems could be resolved in two ways: synthetically modifying the structure or finding new formulations with enhanced properties. The aqueous solubility of metallocenes with cytostatic activities could be enhanced by molecular encapsulation in cyclodextrins, as well as the hydrolytic instability of these compounds could be reduced.

Results

This study presents a theoretical approach on the nanoencapsulation of a series of titanocenes with cytotoxic activity in α-, β-, and γ-cyclodextrin. The HyperChem 5.11 package was used for building and molecular modelling of titanocene and cyclodextrin structures, as well as for titanocene/cyclodextrin complex optimization. For titanocene/cyclodextrin complex optimization experiments, the titanocene and cyclodextrin structures in minimal energy conformations were set up at various distances and positions between molecules (molecular mechanics functionality, MM+). The best interaction between titanocene structures and cyclodextrins was obtained in the case of β- and γ-cyclodextrin, having the hydrophobic moieties oriented to the secondary face of cyclodextrin. The hydrophobicity of titanocenes (logP) correlate with the titanocene-cyclodextrin interaction parameters, especially with the titanocene-cyclodextrin interaction energy; the compatible geometry and the interaction energy denote that the titanocene/β- and γ-cyclodextrin complex can be achieved. Valuable quantitative structure-activity relationships (QSARs) were also obtained in the titanocene class by using the same logP as the main parameter for the in vitro cytotoxic activity against HeLa, K562, and Fem-x cell lines.

Conclusions

According to our theoretical study, the titanocene/cyclodextrin inclusion compounds can be obtained (high interaction energy; the encapsulation is energetically favourable). Further, the most hydrophobic compounds are better encapsulated in β- and γ-cyclodextrin molecules and are more stable (from energetically point of view) in comparison with α-cyclodextrin case. This study suggests that the titanocene / β- and γ-cyclodextrin complexes (or synthetically modified cyclodextrins with higher water solubility) could be experimentally synthesized and could have enhanced cytotoxic activity and even lower toxicity.
An automated plasma protein fractionation design: high-throughput perspectives for proteomic analysis
Authors: Boccardi Claudia , Rocchiccioli Silvia , Cecchettini Antonella , Mercatanti Alberto , Citti Lorenzo
Published: November 2012

Background

Human plasma, representing the most complete record of the individual phenotype, is an appealing sample for proteomics analysis in clinical applications. Up to today, the major obstacle in a proteomics study of plasma is the large dynamic range of protein concentration and the efforts of many researchers focused on the resolution of this important drawback.

Findings

In this study, proteins from pooled plasma samples were fractionated according to their chemical characteristics on a home-designed SPE automated platform. The resulting fractions were digested and further resolved by reversed-phase liquid chromatography coupled with MALDI TOF/TOF mass spectrometry. A total of 712 proteins were successfully identified until a concentration level of ng/mL. Pearson correlation coefficient was used to test reproducibility.

Conclusions

Our multidimensional fractionation approach reduced the analysis time (2 days are enough to process 16 plasma samples filling a 96-well plate) over the conventional gel-electrophoresis or multi-LC column based methods. The robotic processing, avoiding contaminants or lack of sample handling skill, promises highly reproducible specimen analyses (more than 85% Pearson correlation). The automated platform here presented is flexible and easily modulated changing fractioning elements or detectors.
Prevalence of body-focused repetitive behaviors in three large medical colleges of karachi: a cross-sectional study
Authors: Siddiqui Efaza Umar , Naeem Syed Saad , Naqvi Haider , Ahmed Bilal
Published: November 2012

Background

Body-focused repetitive behaviors (BFRBs) that include skin picking (dermatillomania), hair pulling (trichotillomania) and nail biting (onychophagia), lead to harmful physical and psychological sequelae.

The objective was to determine the prevalence of BFRBs among students attending three large medical colleges of Karachi. It is imperative to come up with frequency to design strategies to decrease the burden and adverse effects associated with BFRBs among medical students.

Methods

A cross-sectional study was conducted among 210 students attending Aga Khan University, Dow Medical College and Sind Medical College, Karachi, in equal proportion. Data were collected using a pre tested tool, “Habit Questionnaire”. Diagnoses were made on the criteria that a student must be involved in an activity 5 times or more per day for 4 weeks or more. Convenience sampling was done to recruit the participants aged 18 years and above after getting written informed consent.

Results

The overall prevalence of BFRBs was found to be 46 (22%). For those positive for BFRBs, gender distribution was as follows: females 29 (13.9%) and males 17 (8.1%). Among these students, 19 (9.0%) were engaged in dermatillomania, 28 (13.3%) in trichotillomania and 13 (6.2%) in onychophagia.

Conclusions

High proportions of BFRBs are reported among medical students of Karachi. Key health messages and interventions to reduce stress and anxiety among students may help in curtailing the burden of this disease which has serious adverse consequences.
Dienogest increases the progesterone receptor isoform B/A ratio in patients with ovarian endometriosis
Authors: Hayashi Atsushi , Tanabe Akiko , Kawabe Sachiko , Hayashi Mika , Yuguchi Hiroko , Yamashita Yoshiki , Okuda Kiyoji , Ohmichi Masahide
Published: November 2012

Background

The resistance of endometriotic tissue to progesterone can be explained by alterations in the distribution of progesterone receptor (PR) and estrogen receptor (ER) isoforms. The aims of this study were to examine the expressions of PR-A, PR-B, ERα and ERβ in endometrioma and assess whether these expressions are affected by dienogest or leuprolide acetate (LA) treatment.

Methods

We enrolled 60 females, including 43 patients with endometriosis (14 who received no medical treatment, 13 who received dienogest and 16 who received LA before undergoing laparoscopic surgery) and 17 patients with leiomyoma. The expression levels of PR and ER isoforms in eutopic and ectopic endometrium were assayed with quantitative real-time PCR, and confirmed with immunohistochemistry.

Results

A decreased PR-B/PR-A ratio and an increased ERβ/ERα ratio were demonstrated in ectopic endometrium derived from females with endometriosis compared with the ratios observed in eutopic endometrium obtained from females without endometriosis. Although LA treatment did not affect the PR-B/PR-A and ERβ/ERα ratios, dienogest treatment increased the PR-B/PR-A ratio and decreased the ERβ/ERα ratio in patients with endometriomas.

Conclusions

Dienogest may improve progesterone resistance in endometriotic tissue by increasing the relative expressions of PR-B and PR-A, and decreasing the relative expressions of ERβ and ERα.
Effects of cigarette smoking on priapism induced by quetiapine: a case report
Authors: Hosseini Seyed Hamzeh , Bajoghli Hafez , Ghaeli Padideh
Published: November 2012

Priapism is defined as an unwanted, prolonged, and painful erection which is unrelated to sexual stimulation. Some case studies suggest that priapism is an adverse effect of antipsychotic medications. In our case study a 30 year-old Iranian male with schizophrenia was experiencing recurrent priapism associated with quetiapine use. There are three interesting facts about this case: Firstly, the patient suffered priapism after even low dose consumption of quetiapine. Secondly, this case had experienced priapism with risperidone, olanzapine, and even clozapine in the past, suggesting a possible pharmacodynamic interaction of antipsychotics and inner biological traits in this particular case. Thirdly, priapism induced by low dose quetiapine was resolved after cigarette smoking.
Increasing the risk of spontaneous abortion and major malformations in newborns following use of serotonin reuptake inhibitors during pregnancy: A systematic review and updated meta-analysis
Authors: Nikfar Shekoufeh , Rahimi Roja , Hendoiee Narjes , Abdollahi Mohammad
Published: November 2012

Selective serotonin reuptake inhibitors (SSRIs) are the most frequently used antidepressants during pregnancy. There are conflicting results about their influence on pregnancy outcomes. The goal of this study was to update our previous meta-analysis about pregnancy outcomes following exposure to SSRIs. For this purpose, all relevant databases were searched from 1990 to March 2012 for studies investigating the pregnancy outcomes following exposure to any therapeutic dosage of any SSRI (fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine) during pregnancy. Types of outcome investigated were spontaneous abortion, major malformations, cardiovascular malformations, and minor malformations. A total of 25 studies met our criteria and were included in the meta-analysis. The odds ratio (OD) values are 1.87 (95% CI: 1.5 to 2.33, P< 0.0001) for spontaneous abortion, 1.272 (95% CI: 1.098 to 1.474, P = 0.0014) for major malformations, 1.192 (95% CI: 0.39 to 3.644, P= 0.7578) for cardiovascular malformations, and 1.36 (95% CI: 0.61 to 3.04, P= 0.4498) for minor malformations. The results demonstrated that SSRIs increase the risk of spontaneous abortion and major malformations during pregnancy while they don’t increase the risk of cardiovascular malformations and minor malformations. Our previous meta-analysis only showed an increase in the risk of spontaneous abortion following the use of SSRIs during pregnancy. This might be due to increase in the number of studies included or addition of two new SSRIs (citalopram and escitalopram). The message to researchers is to try considering SSRIs individually during pregnancy to reduce heterogeneity, although all are aware of inevitable limitations to study on pregnant mothers.
Immunosenescence, inflammation and Alzheimer’s disease
Authors: Martorana Adriana , Bulati Matteo , Buffa Silvio , Pellicanò Mariavaleria , Caruso Calogero , Candore Giuseppina , Colonna-Romano Giuseppina
Published: November 2012

Ageing impacts negatively on the development of the immune system and its ability to fight pathogens. Progressive changes in the T-cell and B-cell systems over the lifespan of individuals have a major impact on the capacity to respond to immune challenges. The cumulative age-associated changes in immune competence are termed immunosenescence that is characterized by changes where adaptive immunity deteriorates, while innate immunity is largely conserved or even upregulated with age. On the other hand, ageing is also characterized by “inflamm-ageing”, a term coined to explain the inflammation commonly present in many age-associated diseases. It is believed that immune inflammatory processes are relevant in Alzheimer’s disease, the most common cause of dementia in older people. In the present paper we review data focusing on changes of some immunoinflammatory parameters observed in patients affected by Alzheimer’s disease.
Phenotypic and genetic characterization of Dunaliella (Chlorophyta) from Indian salinas and their diversity
Authors: Preetha Krishna , John Lijo , Subin Cherampillil Sukumaran , Vijayan Koyadan Kizhakkedath
Published: November 2012

Background

The genus Dunaliella (Class – Chlorophyceae) is widely studied for its tolerance to extreme habitat conditions, physiological aspects and many biotechnological applications, such as a source of carotenoids and many other bioactive compounds. Biochemical and molecular characterization is very much essential to fully explore the properties and possibilities of the new isolates of Dunaliella. In India, hyper saline lakes and salt pans were reported to bloom with Dunaliella spp. However, except for the economically important D. salina, other species are rarely characterized taxonomically from India. Present study was conducted to describe Dunaliella strains from Indian salinas using a combined morphological, physiological and molecular approach with an aim to have a better understanding on the taxonomy and diversity of this genus from India.

Results

Comparative phenotypic and genetic studies revealed high level of diversity within the Indian Dunaliella isolates. Species level identification using morphological characteristics clearly delineated two strains of D. salina with considerable β-carotene content (>20 pg/cell). The variation in 18S rRNA gene size, amplified with MA1-MA2 primers, ranged between ~1800 and ~2650 base pairs, and together with the phylogeny based on ITS gene sequence provided a pattern, forming five different groups within Indian Dunaliella isolates. Superficial congruency was observed between ITS and rbcL gene phylogenetic trees with consistent formation of major clades separating Indian isolates into two distinct clusters, one with D. salina and allied strains, and another one with D. viridis and allied strains. Further in both the trees, few isolates showed high level of genetic divergence than reported previously for Dunaliella spp. This indicates the scope of more numbers of clearly defined/unidentified species/sub-species within Indian Dunaliella isolates.

Conclusion

Present work illustrates Indian Dunaliella strains phenotypically and genetically, and confirms the presence of not less than five different species (or sub-species) in Indian saline waters, including D. salina and D. viridis. The study emphasizes the need for a combined morphological, physiological and molecular approach in the taxonomic studies of Dunaliella.
Schistosomiasis control and the health system in P.R. China
Authors: Collins Charles , Xu Jing , Tang Shenglan
Published: November 2012

Over the last sixty years advances have been made in the control of schistosomiasis in P.R. China. There are, however, difficult challenges still to be met. This paper looks at the extent to which the health system offers a positive environment for the control of the disease. It starts by tracing three phases in schistosomiasis control: disease elimination strategy through snail control (1950s-early 1980s); morbidity control strategy based on chemotherapy (mid 1980s to 2003); integrated control strategy (2004+). Each one of these phases took place in distinct policy-making environments. The paper partly draws on these phases to set out five issues of disease control and discusses them in the context of the health system and its recent trends. These cover the policy-making process, intersectoral action for health, equity and access to health services, funding for public goods and externalities, and strengthening resource management and planning. These issues form the basis of an agenda for integrating research and capacity strengthening in the Chinese health system with a view to creating a more positive enabling environment for schistosomiasis control. In so doing it is important to emphasize the role and integrity of the public sector against its commercialization, the underlying value of equity, a systems wide perspective, and the role of advocacy.
Providing financial incentives to rural-to-urban tuberculosis migrants in Shanghai: an intervention study
Authors: Wei Xiaolin , Zou Guanyang , Yin Jia , Walley John , Yang Huaixia , Kliner Merav , Mei Jian
Published: November 2012

Background

Financial issues are major barriers for rural-to-urban migrants accessing tuberculosis (TB) care in China. This paper discusses the effectiveness of providing financial incentives to migrant TB patients (with a focus on poor migrants in one district of Shanghai using treatment completion and default rates), the effect of financial incentives in terms of reducing the TB patient cost, and the incremental cost-effectiveness ratio of the intervention.

Results

Ninety and ninety-three migrant TB patients were registered in the intervention and control districts respectively. TB treatment completion rates significantly improved by 11% (from 78% to 89%) in the intervention district, compared with only a 3% increase (from 73% to 76%) in the control district (P = 0.03). Default rates significantly decreased by 11% (from 22% to 11%) in the intervention district, compared with 1% (from 24% to 23%) in the control district (P = 0.03). In the intervention district, the financial subsidy (RMB 1,080/US$170) accounted for 13% of the average patient direct cost (RMB 8,416/US$1,332). Each percent increase in treatment completion costs required an additional RMB 6,550 (US$1,301) and each percent reduction in defaults costs required an additional RMB 5,240 (US$825) in the intervention district.

Conclusions

Overall, financial incentives proved to be effective in improving treatment completion and reducing default rates among migrant TB patients in Shanghai. The results suggest that financial incentives can be effectively utilized as a strategy to enhance case management among migrant TB patients in large cities in China, and this strategy may be applicable to similar international settings.
Comparative analysis of collagen type II-specific immune responses during development of collagen-induced arthritis in two B10 mouse strains
Authors: Batsalova Tsvetelina , Lindh Ingrid , Bäcklund Johan , Dzhambazov Balik , Holmdahl Rikard
Published: November 2012

Introduction

Immune responses against collagen type II (CII) are crucial for the development of collagen-induced arthritis (CIA). The aim of the present study was to evaluate and compare the CII-directed T cell and antibody specificity at different time points in the course of CIA using two mouse strains on the B10 genetic background - B10.Q, expressing Aq MHC class II molecules, and B10.DR4.Ncf1*/*, expressing human rheumatoid arthritis-associated MHC II DR4 molecules (DRA*0101/DRB*0401).

Methods

B10.Q and B10.DR4.Ncf1*/* mice were immunized with CII emulsified in adjuvant and development of CIA was assessed. T cells from draining lymph nodes were restimulated in vitro with CII peptides and interferon-gamma (IFN-γ) levels in culture supernatants were evaluated by ELISA. CII-specific antibody levels in serum samples were measured by ELISA.

Results

At four different CIA time points we analyzed T cell specificity to the immunodominant CII epitope 259-273 (CII259-273) and several posttranslationally modified forms of CII259-273 as well as antibody responses to three B cell immunodominant epitopes on CII (C1, U1, J1). Our data show that CII-specific T and B cell responses increase dramatically after disease onset in both strains and are sustained during the disease course. Concerning anti-CII antibody fine specificity, during all investigated stages of CIA the B10.Q mice responded predominantly to the C1 epitope, whereas the B10.DR4.Ncf1*/* mice also recognized the U1 epitope. In the established disease phase, T cell reactivity toward the galactosylated CII259-273 peptide was similar between the DR4- and the Aq-expressing strains whereas the response to the non-modified CII peptide was dramatically enhanced in the DR4 mice compared with the B10.Q. In addition, we show that the difference in the transgenic DR4-restricted T cell specificity to CII259-273 is not dependent on the degree of glycosylation of the collagen used for immunization.

Conclusions

The present study provides important evaluation of CII-specific immune responses at different phases during CIA development as well as a comparative analysis between two CIA mouse models. We indicate significant differences in CII T cell and antibody specificities between the two strains and highlight a need for improved humanized B10.DR4 mouse model for rheumatoid arthritis.
Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX
Authors: Coates Alan S , Millar Ewan KA , O'Toole Sandra A , Molloy Timothy J , Viale Giuseppe , Goldhirsch Aron , Regan Meredith M , Gelber Richard D , Sun Zhuoxin , Castiglione-Gertsch Monica , Gusterson Barry , Musgrove Elizabeth A , Sutherland Robert L
Published: November 2012

Introduction

The prognostic significance of p53 protein expression in early breast cancer remains uncertain, with some but not all studies finding an association with poorer outcomes. Estrogen receptor (ER) expression is both a positive prognostic marker and predictive of response to endocrine therapies. The relationship between these biomarkers is unknown.

Methods

We constructed tissue microarrays (TMAs) from available pathological material from 1113 patients participating in two randomized clinical trials comparing endocrine therapy alone versus chemo-endocrine therapy in node-negative breast cancer. Expression of p53 defined as >10% positive nuclei was analyzed together with prior immunohistochemical assays of ER performed at central pathological review of whole tumor sections.

Results

ER was present (i.e. >1% positive tumor cell nuclei) in 80.1% (880/1092). p53 expression was significantly more frequent when ER was absent, 125/212 (59%) than when ER was present, 171/880 (19%), p <0.0001. A significant qualitative interaction was observed such that p53 expression was associated with better disease-free survival (DFS) and overall survival (OS) among patients whose tumors did not express ER, but worse DFS and OS among patients whose tumors expressed ER. The interaction remained significant after allowance for pathologic variables, and treatment. Similar effects were seen when luminal and non-luminal intrinsic subtypes were compared.

Conclusions

Interpretation of the prognostic significance of p53 expression requires knowledge of concurrent expression of ER. The reason for the interaction between p53 and ER is unknown but may reflect qualitatively different p53 mutations underlying the p53 expression in tumors with or without ER expression.

Trial registration

Current Controlled Trials ACTRN12607000037404 (Trial VIII) and ACTRN12607000029493 (Trial IX).
Breast cancer risk assessment across the risk continuum: genetic and nongenetic risk factors contributing to differential model performance
Authors: Quante Anne S , Whittemore Alice S , Shriver Tom , Strauch Konstantin , Terry Mary B
Published: November 2012

Introduction

Clinicians use different breast cancer risk models for patients considered at average and above-average risk, based largely on their family histories and genetic factors. We used longitudinal cohort data from women whose breast cancer risks span the full spectrum to determine the genetic and nongenetic covariates that differentiate the performance of two commonly used models that include nongenetic factors - BCRAT, also called Gail model, generally used for patients with average risk and IBIS, also called Tyrer Cuzick model, generally used for patients with above-average risk.

Methods

We evaluated the performance of the BCRAT and IBIS models as currently applied in clinical settings for 10-year absolute risk of breast cancer, using prospective data from 1,857 women over a mean follow-up length of 8.1 years, of whom 83 developed cancer. This cohort spans the continuum of breast cancer risk, with some subjects at lower than average population risk. Therefore, the wide variation in individual risk makes it an interesting population to examine model performance across subgroups of women. For model calibration, we divided the cohort into quartiles of model-assigned risk and compared differences between assigned and observed risks using the Hosmer-Lemeshow (HL) chi-squared statistic. For model discrimination, we computed the area under the receiver operator curve (AUC) and the case risk percentiles (CRPs).

Results

The 10-year risks assigned by BCRAT and IBIS differed (range of difference 0.001 to 79.5). The mean BCRAT- and IBIS-assigned risks of 3.18% and 5.49%, respectively, were lower than the cohort's 10-year cumulative probability of developing breast cancer (6.25%; 95% confidence interval (CI) = 5.0 to 7.8%). Agreement between assigned and observed risks was better for IBIS (HL X42 = 7.2, P value 0.13) than BCRAT (HL X42 = 22.0, P value <0.001). The IBIS model also showed better discrimination (AUC = 69.5%, CI = 63.8% to 75.2%) than did the BCRAT model (AUC = 63.2%, CI = 57.6% to 68.9%). In almost all covariate-specific subgroups, BCRAT mean risks were significantly lower than the observed risks, while IBIS risks showed generally good agreement with observed risks, even in the subgroups of women considered at average risk (for example, no family history of breast cancer, BRCA1/2 mutation negative).

Conclusions

Models developed using extended family history and genetic data, such as the IBIS model, also perform well in women considered at average risk (for example, no family history of breast cancer, BRCA1/2 mutation negative). Extending such models to include additional nongenetic information may improve performance in women across the breast cancer risk continuum.
What clinicians need to know before assessing risk in sexual offenders
Authors: Darjee Rajan , Russell Katharine
Published: November 2012

This article covers what clinicians need to know before undertaking a risk assessment of a sexual offender. It discusses general information about sexual offenders (characteristics, aetiological models, recidivism rates and legal responses); the association between mental disorders and sexual offending; risk and protective factors; and risk assessment tools.
To scan or not to scan: neuroimaging in mild cognitive impairment and dementia
Authors: Sullivan Victoria , Majumdar Biswadeep , Richman Anna , Vinjamuri Sobhan
Published: November 2012

There is currently a huge variation in clinical practice as to whether patients being assessed for dementia undergo neuroimaging investigations. With an ageing population it is likely that there will be greater pressures on psychogeriatric services, so accurate assessment, diagnosis and prompt treatment will be required. This article will examine the evidence for the use of different neuroimaging techniques in the diagnosis of mild cognitive impairment and dementia.
Supervision: an issue for supervisors and supervisees
Authors: Wickham Jill Munro
Published: November 2012

Supervision, both managerial and clinical, is integral to all areas of practice in health and social care and arguably constitutes the most important aspect of our work. Through supervision, we demonstrate our own suitability and can offer others support in identifying strategies for improvement. It is surprising that many healthcare organisations either do not have a supervision policy or do little to monitor the effectiveness of the supervisory process. The aim of this brief article is to offer a starting point for thought, discussion and reading to motivate and encourage readers to improve their own supervisory practice as supervisor and supervisee.
ADHD with comorbid substance use disorder: review of treatment
Authors: Magon Rakesh , Müller Ulrich
Published: November 2012

Substance use disorders are a frequent comorbidity in adult attention-deficit hyperactivity disorder (ADHD). This review discusses the relationship between adult ADHD and substance use disorder, including use of licit and illicit substances such as nicotine, alcohol, cocaine and cannabis. We discuss treatment studies in this area and provide a treatment algorithm to guide clinicians in the management of adult ADHD comorbid with different forms and severities of substance use disorder.
Is this old age psychiatry's rocket science?
Authors: Jolley David
Published: November 2012

The Bridgend team rightly identifies the need for old age psychiatry services to work effectively with the population and staff of care homes. They describe an interesting and effective approach to this challenge, which will inform others and encourage them to make use of this system or adapt it or other ideas for use in their own locality.
Preventive strategies in depression: gathering evidence for risk
factors and potential interventions
Authors: Berk Michael , Jacka Felice
Published: November 2012

This editorial critiques the recent literature concerning both vitamin D
deficiency in major depression and supplementation as a treatment strategy,
and contextualises it within a broader approach to the prevention of
depression, based on the recent evidence for lifestyle as a risk factor for
depression and anxiety.
Changes in diagnoses before admission to a specialist medium secure unit
Authors: Shetty Amrith , Jayawickrama Dilum , Taylor Pamela J.
Published: November 2012

Aims and method

There is evidence that changing diagnoses may be an important factor preceding homicide, but there is little literature on diagnostic antecedents to admission to specialist secure units after violent behaviour. Our aim was to establish the frequency of a history of changing diagnoses in patients in a UK specialist unit, and to explore the characteristics of these patients.

Results

In total, 38 of 42 study participants had prior contact with psychiatric services. Just over 40% (16 of the 38) had had their diagnosis changed three or more times. All those who had major changes in their diagnosis had received a diagnosis of a psychotic illness at some point prior to the secure unit admission, but then had it withdrawn, only to be restored after prolonged assessment in the secure unit. Personality disorder and substance misuse comorbidity was common in this group; however, non-psychotic diagnoses were seen as more important than psychotic diagnoses by general services.

Clinical implications

Changes in diagnosis between first presentation to psychiatric services and admission to a medium-security unit were more common than would be expected from reports in the general literature. They are a testimony to the difficulties experienced by service providers in delivering a consistent service. This needs to be studied further.
E-learning package on the Mental Capacity Act 2005 for junior doctors and medical students
Authors: Schofield Zena , di Mambro Ben , Schofield Chris
Published: November 2012

Aims and method

The assessment of capacity is integral to all areas of medical practice; however, research has shown that doctors in many specialties have inadequate knowledge about both the Mental Capacity Act and the Mental Health Act. In this study, 39 trainee doctors and 49 fourth-year medical students completed an e-learning package, which included a pre- and post-evaluation of knowledge of the Mental Capacity Act and confidence in the use of this act.

Results

In comparison to pre-intervention scores, trainee doctors and students displayed a statistically significant improvement in knowledge and subjective confidence.

Clinical implications

The e-learning package is an effective educational tool for improving knowledge about the Mental Capacity Act for trainee doctors and could be included as part of induction training for all foundation doctors as well as being considered for use in the induction programme of other trainee doctors. It is an effective tool for educating clinical medical students about the Mental Capacity Act.
Simultaneous PET/MR imaging of the brain: feasibility of cerebral blood flow measurements with FAIR-TrueFISP arterial spin labeling MRI
Authors: Stegger Lars , Martirosian Petros , Schwenzer Nina , Bisdas Sotirios , Kolb Armin , Pfannenberg Christina , Claussen Claus D , Pichler Bernd , Schick Fritz , Boss Andreas
Published: November 2012

Background

Hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) with simultaneous data acquisition promises a comprehensive evaluation of cerebral pathophysiology on a molecular, anatomical, and functional level. Considering the necessary changes to the MR scanner design the feasibility of arterial spin labeling (ASL) is unclear.

Purpose

To evaluate whether cerebral blood flow imaging with ASL is feasible using a prototype PET/MRI device.

Material and Methods

ASL imaging of the brain with Flow-sensitive Alternating Inversion Recovery (FAIR) spin preparation and true fast imaging in steady precession (TrueFISP) data readout was performed in eight healthy volunteers sequentially on a prototype PET/MRI and a stand-alone MR scanner with 128 × 128 and 192 × 192 matrix sizes. Cerebral blood flow values for gray matter, signal-to-noise and contrast-to-noise ratios, and relative signal change were compared. Additionally, the feasibility of ASL as part of a clinical hybrid PET/MRI protocol was demonstrated in five patients with intracerebral tumors.

Results

Blood flow maps showed good delineation of gray and white matter with no discernible artifacts. The mean blood flow values of the eight volunteers on the PET/MR system were 51±9 and 51±7 mL/100 g/min for the 128 × 128 and 192 × 192 matrices (stand-alone MR, 57±2 and 55 ± 5, not significant). The value for signal-to-noise (SNR) was significantly higher for the PET/MRI system using the 192 × 192 matrix size ( P < 0.01), the relative signal change (δS) was significantly lower for the 192 × 192 matrix size ( P = 0.02). ASL imaging as part of a clinical hybrid PET/MRI protocol could successfully be accomplished in all patients in diagnostic image quality.

Conclusion

ASL brain imaging is feasible with a prototype hybrid PET/MRI scanner, thus adding to the value of this novel imaging technique.
The Lalli and Weber effects and the incidence of acute non-renal adverse reactions to contrast media
Authors: Thomsen Henrik S , Webb Judith
Published: November 2012

Some radiologists have learned that their manner and manifest anxiety render them unsuitable agents for the administration of contrast media. I would recommend that individuals injecting these materials adopt the mien of equanimity urged upon us by Sir William Osler, treat their patients with gentleness and inapparent concern and not arouse their anxieties or increase their fear.” Anthony LF Lalli, 1980 ( 1 )
What is the NHS Safety Thermometer?
Authors: Power Maxine , Stewart Kevin , Brotherton Ailsa
Published: November 2012

The English National Health Service (NHS) announced a new programme to incentivize use of the NHS Safety Thermometer (NHS ST) in the NHS Operating Framework for 2012/13. For the first time, the NHS is using the Commissioning for Quality and Innovation (CQUIN) scheme, a contract lever, to incentivize ALL providers of NHS care to measure four common complications (harms) using the NHS ST in a proactive way on one day per month. This national CQUIN scheme provides financial reward for the collection of baseline data with a view to incentivizing the achievement of improvement goals in later years. In this paper, we describe the rationale for this large-scale data collection, the purpose of the instrument and its potential contribution to our current understanding of patient safety. It is not a comprehensive description of the method or preliminary data. This will be published separately. The focus of the NHS ST on pressure ulcers, falls, catheters and urine infection and venous thromboembolism is broadly applicable to patients across all healthcare settings, but is specifically pertinent to older people who, experiencing more healthcare intervention, are at risk of not one but multiple harms. In this paper, we also describe an innovative patient-level composite measure of the absence of harm from the four identified, termed as “harmfreecare” which is unique to the NHS ST and is under development to raise standards for patient safety.
Metastatic disease around the hip
Authors: Haidukewych G. J.
Published: November 2012

Many tumors metastasise to bone, therefore, pathologic fracture and impending pathologic fractures are common reasons for orthopedic consultation. Having effective treatment strategies is important to avoid complications, and relieve pain and preserve function. Thorough pre-operative evaluation is recommended for medical optimization and to ensure that the lesion is in fact a metastasis and not a primary bone malignancy. For impending fractures, various scoring systems have been proposed to determine the risk of fracture, and therefore the need for prophylactic stabilisation. Lower score lesions can often be treated with radiation, while more problematic lesions may require internal fixation. Intramedullary fixation is generally preferred due to favorable biomechanics. Arthroplasty may be required for lesions with massive bony destruction where internal fixation attempts are likely to fail. Radiation may also be useful postoperatively to minimise construct failure due to tumor progression.
Large diameter heads
Authors: Rodriguez J. A. , Rathod P. A.
Published: November 2012

Large femoral heads have been used with increasing frequency over the last decade. The prime reason is likely the effect of large heads on stability. The larger head neck ratio, combined with the increased jump distance of larger heads result in a greater arc of impingement free motion, and greater resistance to dislocation in a provocative position. Multiple studies have demonstrated clear clinical efficacy in diminishing dislocation rates with the use of large femoral heads. With crosslinked polyethylene, wear has been shown to be equivalent between larger and smaller heads. However, the stability advantages of increasing diameter beyond 38 mm have not been clearly demonstrated. More importantly, recent data implicates large heads in the increasing prevalence of groin pain and psoas impingement. There are clear benefits with larger femoral head diameters, but the advantages of diameters beyond 38 mm have not yet been demonstrated clinically.
Hip and knee arthroplasty 2011
Authors: Rosenberg A. G. , Berend M. E. , Berry D. J. , Della Valle C. J. , MacDonald S. J. , Minas T.
Published: November 2012

This conversation represents an attempt by several arthroplasty surgeons to critique several abstracts presented over the last year as well as to use them as a jumping off point for trying to figure out where they fit in into our current understanding of multiple issues in modern hip and knee arthroplasty.
Fixed flexion deformity and total knee arthroplasty
Authors: Su E. P.
Published: November 2012

Fixed flexion deformities are common in osteoarthritic knees that are indicated for total knee arthroplasty. The lack of full extension at the knee results in a greater force of quadriceps contracture and energy expenditure. It also results in slower walking velocity and abnormal gait mechanics, overloading the contralateral limb. Residual flexion contractures after TKA have been associated with poorer functional scores and outcomes.

Although some flexion contractures may resolve with time after surgery, a substantial percentage will become permanent. Therefore, it is essential to correct fixed flexion deformities at the time of TKA, and be vigilant in the post-operative course to maintain the correction.

Surgical techniques to address pre-operative flexion contractures include: adequate bone resection, ligament releases, removal of posterior osteophytes, and posterior capsular releases. Post-operatively, extension can be maintained with focused physiotherapy, a specially modified continuous passive motion machine, a contralateral heel lift, and splinting.
Role and results of tapered fluted modular titanium stems in revision total hip arthroplasty
Authors: Munro J. T. , Garbuz D. S. , Masri B. A. , Duncan C. P.
Published: November 2012

Tapered, fluted, modular, titanium stems have a long history in Europe and are increasing in popularity in North America. We have reviewed the results at our institution looking at stem survival and clinical outcomes. Radiological outcomes and quality of life assessments have been performed and compared to cylindrical non-modular cobalt chromium stems. Survival at five years was 94%. This fell to 85% at ten years due to stem breakage with older designs. Review of radiology showed maintenance or improvement of bone stock in 87% of cases. Outcome scores were superior in tapered stems despite worse pre-operative femoral deficiency. Tapered stems have proved to be a useful alternative in revision total hip arthroplasty across the spectrum of femoral bone deficiency.
Intra-operative fractures during THA
Authors: Mayle R. E. , Della Valle C. J.
Published: November 2012

The purpose of this paper is to discuss the risk factors, prevention strategies, classification, and treatment of intra-operative femur fractures sustained during primary and revision total hip arthroplasty.
Minimising blood loss and transfusion in contemporary hip and knee arthroplasty
Authors: Watts C. D. , Pagnano M. W.
Published: November 2012

Despite advances in contemporary hip and knee arthroplasty, blood loss continues to be an issue. Though blood transfusion has long been used to treat post-operative anemia, the associated risks are well established. The objective of this article is to present two practical and effective approaches to minimising blood loss and transfusion rates in hip and knee arthroplasty: the use of antifibrinolytic medications such as tranexamic acid and the adoption of more conservative transfusion indications.
Metal-on-metal hip arthroplasty
Authors: Benjamin-Laing H. , Haddad F. S.
Published: November 2012

In this paper, we will consider the current role of metal-on-metal bearings by looking at three subtypes of MoM hip arthroplasty separately: Hip resurfacing, large head (> 36 mm) MoM THA and MoM THA with traditional femoral head sizes.
Wound closure
Authors: Vince K. G.
Published: November 2012

In this paper, we consider wound healing after total knee arthroplasty.
The painful hip
Authors: Schmalzried T. P.
Published: November 2012

The differential diagnosis of the painful total hip arthroplasty (resurfacing or total hip) includes infection, failure of fixation (loosening), tendinitis, bursitis, synovitis, adverse local tissue reaction (ALTR) to cobalt-chromium alloys, and non-hip issues, such as spinal disorders, hernia, gynecologic, and other pelvic pain. Assuming that the hip is the source of pain, the first level question is prosthetic or non-prosthetic pain generator? The second level prosthetic question is septic or aseptic? The third level question (aseptic hips) is well-fixed or loose? ALTR is best diagnosed by cross-sectional imaging. Successful treatment is dependent on correct identification and elimination of the pain generator. Treatment recommendations for ALTR and taper corrosion are evolving.
Cementless fixation in total knee arthroplasty
Authors: Drexler M. , Dwyer T. , Marmor M. , Abolghasemian M. , Sternheim A. , Cameron H. U.
Published: November 2012

In this study we present our experience with four generations of uncemented total knee arthroplasty (TKA) from Smith & Nephew: Tricon M, Tricon LS, Tricon II and Profix, focusing on the failure rates correlating with each design change. Beginning in 1984, 380 Tricon M, 435 Tricon LS, 305 Tricon 2 and 588 Profix were implanted by the senior author. The rate of revision for loosening was 1.1% for the Tricon M, 1.1% for the Tricon LS, 0.5% for the Tricon 2 with a HA coated tibial component, and 1.3% for the Profix TKA. No loosening of the femoral component was seen with the Tricon M, Tricon LS or Tricon 2, with no loosening seen of the tibial component with the Profix TKA. Regarding revision for wear, the incidence was 13.1% for the Tricon M, 6.6% for the Tricon LS, 2.3% for the Tricon 2, and 0% for the Profix. These results demonstrate that improvements in the design of uncemented components, including increased polyethylene thickness, improved polyethylene quality, and the introduction of hydroxyapatite coating, has improved the outcomes of uncemented TKA over time.
Simultaneous-bilateral TKA
Authors: Parvizi J. , Rasouli M. R.
Published: November 2012

In this paper, we will consider the current role of simultaneous-bilateral TKA. Based on available evidence, it is our opinion that simultaneous bilateral TKA carries a higher risk of morbidity and mortality and should be reserved for select few.
Simultaneous-bilateral TKA
Authors: Sculco T. P. , Sculco P. K.
Published: November 2012

In this paper, we will consider the current role of simultaneous-bilateral TKA. Based on available evidence, it is our opinion that bilateral one stage TKR is a safe and efficacious treatment for patients with severe bilateral arthritic knee disease but should be reserved for selected patients without significant medical comorbidities.
The evolving incidence and reasons for re-operation after fixed-bearing PCL retaining total knee arthroplasty
Authors: Scott R. D.
Published: November 2012

PCL retaining fixed-bearing TKA is a highly successful operation with the need for more surgery occurring at the rate of approximately 0.4% per year over the first 27 years. The most common cause for revision surgery is related to polyethylene insert failure and accounts for approximately 50% of re-operations. Late metastatic infection is the next most frequent cause followed by patellar problems, late instability and component loosening in decreasing frequency. A myriad of rare miscellaneous problems can also occur.
Use of Romiplostim in a Hemodialysis Patient with Primary Immune Thrombocytopenia
Authors: Al-Jafar Hassan , Giagounidis Aristoteles , El-Rashaid Kamel , Al-Ali Masouma , Hakim Abbas A
Published: November 2012

OBJECTIVE:

To present the case of a patient with primary immune thrombocytopenia (ITP), renal impairment, and chronic hepatitis C virus (HCV) infection who was treated with platelet transfusions, intravenous immunoglobulin (IVIG), corticosteroids, eltrombopag, rituximab, and romiplostim in an attempt to raise platelet counts to a clinically acceptable level.

CASE SUMMARY:

A 71-year-old man with end-stage renal disease (ESRD) was on maintenance hemodialysis and had long-term diabetes mellitus, chronic obstructive pulmonary disease, and other comorbidities. He was admitted with epistaxis, severe thrombocytopenia, and a platelet count of 4 × 109/L. Platelet transfusions, treatment with IVIG, corticosteroids, eltrombopag, and rituximab resulted in transient and inadequate increases in platelet counts. Further bleeding manifestations, including epistaxis, melena, hematomas, and ecchymotic patches prompted treatment with blood product concentrates and a higher dose of eltrombopag, resulting in a further lack of clinical response. After 6 weeks of failed treatment attempts, initiation of weekly treatment with romiplostim 5 μg/kg resulted in rapid stabilization (within a week) of platelet counts in the range of 200 × 109/L. The patient was discharged, with subsequent dose adjustment of weekly romiplostim treatment to 2.5 μg/kg, continued hemodialysis, and a return to normal daily activities.

DISCUSSION:

The primary clinical concern in this elderly patient with multiple comorbidities was to lower the bleeding risk associated with consistent thrombocytopenia. Despite the lack of clinical data to support the efficacy and safety of romiplostim in patients with ITP and renal impairment, stimulation of platelet production with romiplostim was a reasonable approach in view of the bleeding risk and following nonresponse to treatment with corticosteroids, IVIG, eltrombopag, and rituximab. To our knowledge, this case represents the first successful use of romiplostim to manage primary ITP in the presence of ESRD and concurrent chronic HCV infection in a patient on hemodialysis.

CONCLUSIONS:

Romiplostim appears to be a viable option for treatment of ITP in a patient with ESRD and chronic HCV infection following nonresponse to treatment with corticosteroids, IVIG, eltrombopag, and rituximab.