bluuebunny/crossref_metadata_2025 huggingface dataset:
External and internal ophthalmoplegia, facial diplegia, ataxia and exaggerated deep tendon reflexes associated with anti-GQ1b antibodies: A new variant of acute ophthalmoparesis
Authors: Morrison Ian , Razvi Saif S.M. , Metcalfe Richard A. , Duncan Rod
Published: March 2011

We present the case report of a patient with antibodies to ganglioside GQ1b, who presented with pupillary areflexia, external ophthalmoplegia, ataxia, brisk deep tendon reflexes and facial muscle diplegia following a viral illness. The patient was diagnosed with acute ophthalmoparesis, which is a rare variant of Miller Fisher syndrome that has been characterised recently. We describe a unique presentation of this rare condition, and consider the range of presentations that can occur in association with antibodies to the GQ1b ganglioside.
Head Injury
Authors: Hureibi KA , McLatchie GR
Published: March 2011

Head injury is one of the commonest injuries in sport. Most are mild but some can have serious outcomes. Sports medicine doctors should be able to recognise the clinical features and evaluate athletes with head injury. It is necessary during field assessment to recognise signs and symptoms that help in assessing the severity of injury and making a decision to return-to-play. Prevention of primary head injury should be the aim. This includes protective equipment like helmets and possible rule changes.
Drugs and Sport
Authors: Pai S , McLatchie G R
Published: March 2011

There has always been the temptation to take prohibited substances in the struggle for an athlete to gain the ‘higher ground’ above the rest of the competitors which allow goals to be attained easier than by the conventional training methods.

The problem of drugs in sport has existed for a long time and is underestimated in its prevalence. This paper deals with the reasons of why athletes take such drugs, which drugs are available and the testing employed to detect their use.

Among the issues discussed will be the future of drugs in sport and what measures can be taken to combat their use.
A Metachronous Case of Gastric Lymphoma and Gastric Adenocarcinoma
Authors: Lyon A , Crozier JEM , Mitchell KG
Published: March 2011

The occurrence of gastric adenocarcinoma and gastric lymphoma in the same patient is very rare despite a major shared risk factor in the form of Helicobacter pylori infection. We report on a 48 year old who presented with MALT lymphoma, managed with Helicobacter eradication therapy, who presented with gastric adenocarcinoma ten years later. We suggest that MALT lymphoma patients may require extended follow up, or indeed could benefit from regular H. pylori screening programmes.
Cyclospora cayetanensis causing diarrhoea in adults in Norfolk, England: report of two cases and review of literature
Authors: Sajjad Raja N , Schelenz S
Published: March 2011

Cyclospora cayetanensis is an important emerging infectious disease agent found worldwide causing cyclosporiasis; a condition presenting with prolonged and profuse diarrhoea in immunocompetent and immunocompromised (such as AIDS) patients. It is endemic in some tropical regions of the world and mostly associated with travel to these areas. The prevalence of Cyclospora cayetanensis in the UK remains very low. Cases of cyclosporiasis are often misdiagnosed or even missed due to the lack of understanding of the epidemiological and laboratory features of this pathogen. In this report a 42 year old male animal farm worker and a 45 year old female patient presented with the signs and symptoms of a gastrointestinal illness over a period of several weeks. Cyclospora cayetanensis oocysts were detected in stool specimens. Oral Trimethoprim-sulfamethaxazole 160/800 mg twice daily for 10 days was administered in first patient while second patient improved without specific treatment. This is a first example of a possible link between animals to human spread of Cyclospora cayetanensis in one of the cases. The authors also review the previously reported cyclosporiasis cases in the literature.
Groin Pain in Athletes
Authors: Hureibi KA , McLatchie GR
Published: March 2011

Groin pain in athletes is a common problem in sport medicine, and remains a diagnostic challenge. It is more common with sports that involve kicking, rapid accelerations and decelerations, and sudden direction changes. There is an extensive differential diagnosis and overlap in signs between possible diagnoses. It is important to appreciate the anatomy of the groin and undertake a careful history and examination. Adductor strain, groin disruption and osteitis pubis are among the common causes. The aim of this article is to briefly review the most common causes of groin pain in athletes. The diagnosis and management of these conditions are briefly discussed.
Equality of Access to “Fast-Track” Stroke Services in an Older, Socio-Economically Deprived Scottish Population
Authors: Quinn TJ , Dawson J , Walters MR
Published: March 2011

Background and Aims

Unequal access to specialist stroke services may contribute to the disproportionate stroke burden in certain populations. We evaluated the relationship between access to TIA services, deprivation and age.

Methods

We prospectively recorded referral pattern data on consecutive TIA service patients. Socio-economic deprivation was derived from postcode and census data. Associations were described using Kruskal-Wallis statistics.

Results

Of 3,462 patients assessed, there was no association between time to clinic referral or attendance and increasing deprivation or age.

Conclusion

Inequality of access to TIA services for older, deprived patients was not evident. However, delay to assessment and prevalence of risk factors was substantial for all patients.
Crohn's Disease Incidence in NHS Tayside
Authors: Steed H , Walsh S , Reynolds N
Published: March 2011

Background & Aims

The incidence of Crohn's disease (CD) in northeastern Scotland was last reported as rising in the 1980's, while in the rest of Europe it had reached steady state. This study reviewed the incidence of CD in NHS Tayside.

Methods

Data was collected retrospectively and analysed using age and sex standardization, socioeconomic factors and urban and rural postcodes.

Results

A point prevalence of 157 per 100,000 population in the Tayside region was found. The average incidence of CD was 9.56 per 100,000 per year between 2003 and 2007 and 7.16 per 100,000 per year between 1998 and 2001. There was no link to urbanization and no difference in incidence between the sexes. Incidence was not related to affluence in this population and peak age of onset occurred in the third decade of life only. 12.7% of patients had a family history of inflammatory bowel disease and 25% of patients were current smokers.

Conclusions

The incidence of CD appears to have arrived at a steady state in Tayside, while recent evidence suggests that it is on the rise in Scandinavia again. The results of the genetic studies to come from the east of Scotland are eagerly awaited to help shed light on the aetiology of this complex disorder.
Obstetric Care of New European Migrants in Scotland: an audit of antenatal care, obstetric outcomes and communication
Authors: Bray JK , Gorman DR , Dundas K , Sim J
Published: March 2011

Background and Aims

There has been a twelve-fold increase in the number of New European migrants giving birth in Lothian between 2004 and 2007. The objective of this study was to audit obstetric care standards in Lothian for new migrants and recommend service improvements.

Methods

A retrospective audit of 114/136 (84%) obstetric case records of new European migrants giving birth in Lothian hospitals in 2006 was conducted. Assessment was against care standards for antenatal booking, antenatal attendance and interpretation. Obstetric outcomes were audited against the general population.

Results

Eighty percent were primiparous. Fifty five percent had booked by the end of week 14. Mean birth weights and lengths of stay were similar to the general population. Intervention rates were 23% for Caesarean Sections (C/S) and 17% for instrumental deliveries (versus 27% and 19% respectively in the general population). Epidural or spinal anaesthesia was used for 57% compared to 50% of the general population. The interpretation services (ITS) were used infrequently.

Conclusions

Full compliance with antenatal and interpretation standards was not achieved for this population. ITS was most commonly used to meet the needs of healthcare professionals, rather than as a routine. While there were no significant differences in maternity outcomes, poor communication did affect care.
Primary adenocarcinoma of the Meckel's diverticulum presenting with small bowel obstruction: a case and brief review of the literature
Authors: Parameswaran R , Bapu D , McLaren A
Published: March 2011

Tumours of the Meckel's diverticulum are uncommon, with carcinoid tumours being the commonest type. Primary adenocarcinomas are extremely rare, but when seen are from gastric or pancreatic heterotopic cells. We report a case of primary intestinal adenocarcinoma arising in a Meckel's diverticulum in a 36 year old man, presenting with small bowel obstruction. The patient had a successful outcome following surgical resection.
Scottish Survey of Public Place Defibrillators
Authors: Ashimi AO , Cobbe SM , Pell JP
Published: March 2011

Background

Public place defibrillators can reduce delays to defibrillation but their cost-effectiveness has not been evaluated in randomised trials. In Scotland, unlike England, no health sector funding has been provided. Nonetheless, anecdotal evidence suggests they are increasing in number.

Methods

A cross-sectional survey was conducted of all airports, shopping malls, leisure centres, and major train and bus stations to determine whether defibrillators had been purchased and by whom, the training and maintenance arrangements, and whether they had been discharged.

Results

Of the 183 eligible sites, 153 (84%) participated. 33 (22%) had at least one defibrillator. Those in airports and shopping malls were purchased privately. Those in leisure centres were bought by charities or local authorities. The majority (97%) provided training to existing staff, but 6 (18%) provided no training to new staff. Only 6 (18%) had a maintenance agreement and 8 (24%) a replacement policy. Only one site permitted public access. Defibrillators had been discharged in 10 (30%) sites. Of the 32 people shocked, 23 (72%) survived until the ambulance arrived.

Conclusions

Despite absence of health sector funding, defibrillators are located in 22% of high footfall public places. Those purchasing defibrillators need to ensure adequate maintenance, replacement and training arrangements.
Effect of withdrawing topical fusidic acid on Staphylococcus aureus resistance rates
Authors: Wylie G , Dancer S J , Bilsland D
Published: March 2011

A previous local study revealed high levels of fusidic acid (FA) resistance within dermatology. It was therefore decided to limit use of topical FA within dermatology and then assess the effect on resistance rates. The local microbiology department produced FA resistance data within dermatology over a five-year period. This was then compared with data provided for four other control specialties. Since withdrawal of FA in dermatology, between 2002 and 2006, there was a statistically significant fall in FA resistance rates, while the other four control specialty areas showed increases in resistance rates. In conclusion, it would appear that, in dermatology, withdrawal of topical FA could have a beneficial effect on overall resistance rates for this antibiotic. Given these findings, we made recommendations that other local dermatology units consider their policy on the routine use of topical fusidic preparations.
An unusual infection in an injecting drug user
Authors: Gillis K , Seenan J P , Cahill A , Tyers A , Khanna N , Edwards G F S , Diggle M A
Published: March 2011

Injecting drug users are prone to atypical infections. We present a case of septic thrombophlebitis secondary to Fusobacterium gonidiaformans infection in a heroin user, which demonstrates the frequently unusual nature of pathogens and presentations in this group of patients.
Degos Disease
Authors: Magro Cynthia M. , Poe Jonathan C. , Kim Connie , Shapiro Lee , Nuovo Gerard , Crow Mary K. , Crow Yanick J.
Published: March 2011

Degos disease is a lethal small vessel angiopathy targeting the skin, gastrointestinal tract, and central nervous system, potentially developing in the setting of known autoimmune disease, although forme fruste primary variants exist. Its pathogenetic basis is unknown.

Four cases of Degos disease were encountered in archival material, representing 2 men, ages 38 and 43 years, and 2 females, ages 48 and 2 years; 3 patients died of disease. All had characteristic skin lesions with gastrointestinal involvement; other affected organs included brain in one and pericardium and pleura in another. Skin biopsies showed pauci-inflammatory thrombogenic microangiopathy with endothelial cell injury. Extracutaneous organs demonstrated fibromucinous occlusive arteriopathy. Prominent vascular C5b-9 was seen in the skin, gastrointestinal tract, and brain. All cases had evidence of high expression of interferon-α (based on tissue expression of MXA, a type I interferon-inducible protein), endothelial tubuloreticular inclusions, and an interferon gene signature in peripheral blood mononuclear cells. The MXA expression paralleled the pattern of C5b-9 deposition.

Degos disease is a distinct vascular injury syndrome whereby a dysregulated interferon-α response in concert with membranolytic attack complex deposition may contribute to the unique vascular changes. Understanding the pathophysiology of the disease process could lead to more directed therapies, including terminal complement inhibition with agents such as eculizumab.
Pathology Consultation on Reporting of Critical Values
Authors: Genzen Jonathan R. , Tormey Christopher A.
Published: March 2011

Among the most important functions of a pathology or laboratory medicine service is the clear, accurate, and rapid communication of critical test results (critical values) to patient care providers. Pathologists and laboratory professionals are often confronted with many obstacles in the reporting of such critical values, including establishing clinically relevant criteria for critical values, resolving difficulties in locating an ordering provider when a critical value is obtained, and ensuring that the provider understands the severity and implications of a critical result when he or she has questions. This article presents a hypothetical (yet fairly common) clinical case scenario regarding critical values and then provides an up-to-date discussion and review of the literature on the reporting of critical results.
The Prognostic Impact of Sex on Surgically Resected Non–Small Cell Lung Cancer Depends on Clinicopathologic Characteristics
Authors: Sterlacci William , Tzankov Alexandar , Veits Lothar , Oberaigner Wilhelm , Schmid Thomas , Hilbe Wolfgang , Fiegl Michael
Published: March 2011

The increasing incidence of lung cancer in women and their supposed survival advantage over men requires clarification of the significance of sex. Age, stage, histologic features, differentiation grade, and Ki-67 index were assessed in 405 surgically resected non–small cell lung cancers (NSCLCs) using a standardized tissue microarray platform.

Women were associated with well/moderate tumor differentiation, a Ki-67 index of 3% or less, and adenocarcinoma histologic features. Female sex predicted increased survival time only by univariate analysis. Stratified by sex, increased survival was noted for women older than 64 years, with a tumor at postsurgical International Union Against Cancer stage I, with adenocarcinoma histologic features, with well- or moderately differentiated tumors, or with a Ki-67 index of 3% or less.

Sex is not an independent prognostic parameter for patients with surgically resected NSCLC. Sex-linked differences are associated with other factors, thus simulating a prognostic impact of sex. This study elucidates sex-specific interactions between patient and tumor characteristics, which are pivotal toward improving prognostic accuracy, individualized therapies, and screening efforts.
Necessarily a narrator or narrator if necessary: A short note on a long subject words
Authors: Margolin Uri
Published: March 2011

For (at least) literary narratives I propose to understand “narrator” as follows: An inner-textual speech position from which the current narrative discourse as a whole originates, and from which references to the entities, actions and events that this discourse is about are being made. Through a dual process of metonymic transfer and anthropomorphisation the term “narrator” is then employed to designate a presumed occupant of this position, the hypothesized producer of the current discourse. A narrator is a linguistically indicated, textually projected and readerly identified position whose occupant needs to be thought of primarily in terms of a communicative role, distinct from any actualworld flesh-and-blood (or computer) producer of the text. The paper describes in brief eight different kinds of general considerations (linguistic, philosophical, methodological and general literary-theoretical) which can motivate a narratologist to judge the narrator category/instance as an indispensable or as a merely optional element of his general model of literary narrative. The article concludes with two recent theoretical moves which tend to circumvent the need for such a choice by either re-drawing the narratologist's domain of objects or by redefining the status of the narrator category itself.
Acid Fibroblast Growth Factor and Peripheral Nerve Grafts Regulate Th2 Cytokine Expression, Macrophage Activation, Polyamine Synthesis, and Neurotrophin Expression in Transected Rat Spinal Cords
Authors: Kuo Huai-Sheng , Tsai May-Jywan , Huang Ming-Chao , Chiu Chuan-Wen , Tsai Ching-Yi , Lee Meng-Jen , Huang Wen-Cheng , Lin Yi-Lo , Kuo Wen-Chun , Cheng Henrich
Published: March 2011

Spinal cord injury elicits an inflammatory response that recruits macrophages to the injured spinal cord. Quantitative real-time PCR results have shown that a repair strategy combining peripheral nerve grafts with acidic fibroblast growth factor (aFGF) induced higher interleukin-4 (IL-4), IL-10, and IL-13 levels in the graft areas of rat spinal cords compared with transected spinal cords at 10 and 14 d. This led to higher arginase I-positive alternatively activated macrophage (M2 macrophage) responses. The gene expression of several enzymes involved in polyamine biosynthesis pathways was also upregulated in the graft areas of repaired spinal cords. The treatment induced a twofold upregulation of polyamine levels at 14 d, as confirmed by HPLC. Polyamines are important for the repair process, as demonstrated by the observation that treatment with inhibitors of arginase I and ornithine decarboxylase attenuates the functional recoveries of repaired rats. After 14 d, the treatment also induced the expression of neurotrophin nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as M2 macrophages within grafted nerves expressing BDNF. IL-4 was upregulated in the injury sites of transected rats that received aFGF alone compared with those that received nerve grafts alone at 10 d. Conversely, nerve graft treatment induced NGF and BDNF expression at 14 d. Macrophages expressing polyamines and BDNF may benefit axonal regeneration at 14 d. These results indicate that aFGF and nerve grafts regulate different macrophage responses, and M2 macrophages may play an important role in axonal regeneration after spinal cord injury in rats.
Neuronal Correlates of Cross-Modal Transfer in the Cerebellum and Pontine Nuclei
Authors: Campolattaro Matthew M. , Kashef Alireza , Lee Inah , Freeman John H.
Published: March 2011

Cross-modal transfer occurs when learning established with a stimulus from one sensory modality facilitates subsequent learning with a new stimulus from a different sensory modality. The current study examined neuronal correlates of cross-modal transfer of pavlovian eyeblink conditioning in rats. Neuronal activity was recorded from tetrodes within the anterior interpositus nucleus (IPN) of the cerebellum and basilar pontine nucleus (PN) during different phases of training. After stimulus preexposure and unpaired training sessions with a tone conditioned stimulus (CS), light CS, and periorbital stimulation unconditioned stimulus (US), rats received associative training with one of the CSs and the US (CS1–US). Training then continued on the same day with the other CS to assess cross-modal transfer (CS2–US). The final training session included associative training with both CSs on separate trials to establish stronger cross-modal transfer (CS1/CS2). Neurons in the IPN and PN showed primarily unimodal responses during pretraining sessions. Learning-related facilitation of activity correlated with the conditioned response (CR) developed in the IPN and PN during CS1–US training. Subsequent CS2–US training resulted in acquisition of CRs and learning-related neuronal activity in the IPN but substantially less little learning-related activity in the PN. Additional CS1/CS2 training increased CRs and learning-related activity in the IPN and PN during CS2–US trials. The findings suggest that cross-modal neuronal plasticity in the PN is driven by excitatory feedback from the IPN to the PN. Interacting plasticity mechanisms in the IPN and PN may underlie behavioral cross-modal transfer in eyeblink conditioning.
Thalamic T-Type Ca2+Channels Mediate Frontal Lobe Dysfunctions Caused by a Hypoxia-Like Damage in the Prefrontal Cortex
Authors: Kim Jeongjin , Woo Jeonghoon , Park Young-Gyun , Chae Sujin , Jo Seonmi , Choi Jeong Woo , Jun Hong Young , Yeom Young Il , Park Seong Hoon , Kim Kyung Hwan , Shin Hee-Sup , Kim Daesoo
Published: March 2011

Hypoxic damage to the prefrontal cortex (PFC) has been implicated in the frontal lobe dysfunction found in various neuropsychiatric disorders. The underlying subcortical mechanisms, however, have not been well explored. In this study, we induced a PFC-specific hypoxia-like damage by cobalt-wire implantation to demonstrate that the role of the mediodorsal thalamus (MD) is critical for the development of frontal lobe dysfunction, including frontal lobe-specific seizures and abnormal hyperactivity. Before the onset of these abnormalities, the cross talk between the MD and PFC nuclei at theta frequencies was enhanced. During the theta frequency interactions, burst spikes, known to depend on T-type Ca2+channels, were increased in MD neurons.In vivoknockout or knockdown of the T-type Ca2+channel gene (CaV3.1) in the MD substantially reduced the theta frequency MD–PFC cross talk, frontal lobe-specific seizures, and locomotor hyperactivity in this model. These results suggest a two-step model of prefrontal dysfunction in which the response to a hypoxic lesion in the PFC results in abnormal thalamocortical feedback driven by thalamic T-type Ca2+channels, which, in turn, leads to the onset of neurological and behavioral abnormalities. This study provides valuable insights into preventing the development of neuropsychiatric disorders arising from irreversible PFC damage.
Dopamine, But Not Serotonin, Regulates Reversal Learning in the Marmoset Caudate Nucleus
Authors: Clarke Hannah F. , Hill Gemma J. , Robbins Trevor W. , Roberts Angela C.
Published: March 2011

Studies of visual discrimination reversal learning have revealed striking neurochemical dissociations at the level of the orbitofrontal cortex (OFC) with serotoninergic, but not dopaminergic, integrity being important for successful reversal learning. These findings have considerable implications for disorders such as obsessive compulsive disorder and schizophrenia, in which reversal learning is impaired, and which are primarily treated with drugs targeting the dopaminergic and serotoninergic systems. Dysfunction in such disorders however, is not limited to the OFC and extends subcortically to other structures implicated in reversal learning, such as the medial caudate nucleus. Therefore, because the roles of the serotonin and dopamine within the caudate nucleus are poorly understood, this study compared the effects of selective serotoninergic or selective dopaminergic depletions of the marmoset medial caudate nucleus on serial discrimination reversal learning.

All monkeys were able to learn novel stimulus–reward associations but, unlike control monkeys and monkeys with selective serotoninergic medial caudate depletions, dopamine-depleted monkeys were markedly impaired in their ability to reverse this association. This impairment was not perseverative in nature. These findings are the opposite of those seen in the OFC and provide evidence for a neurochemical double dissociation between the OFC and medial caudate in the regulation of reversal learning. Although the specific contributions of these monoamines within the OFC–striatal circuit remain to be elucidated, these findings have profound implications for the development of drugs designed to remediate some of the cognitive processes underlying impaired reversal learning.
Neural Substrate of Spatial Memory in the Superior Colliculus after Damage to the Primary Visual Cortex
Authors: Takaura Kana , Yoshida Masatoshi , Isa Tadashi
Published: March 2011

In the primate brain, the primary visual cortex (V1) is a major source of visual information processing in the cerebral cortex, although some patients and monkeys with damage to the V1 show visually guided behaviors in the visual field affected by the damage. Until now, behaviors of the surviving brain regions after damage to V1 and their contribution to the residual visual functions remain unclear. Here, we report that the monkeys with a unilateral lesion of V1 can make not only visually guided saccades but also memory-guided saccades (MGS) into the affected visual field. Furthermore, while the monkeys were performing the MGS task, sustained activity was observed in a large fraction of the neurons in the superior colliculus ipsilateral to the lesion, which has been supposed as a key node for recovery after damage to V1. These neurons maintained the spatial information throughout the delay period regardless of whether they exhibited saccadic bursts or not, which was not the case on the intact side. Error analysis revealed that the sustained activity was correlated with monkeys' behavioral outcome. These results suggest that the ipsilesional SC might function as a neural substrate for spatial memory in the affected visual field. Our findings provide new insight into the understanding of the compensatory mechanisms after damage to V1.
TRIP8b Regulates HCN1 Channel Trafficking and Gating through Two Distinct C-Terminal Interaction Sites
Authors: Santoro Bina , Hu Lei , Liu Haiying , Saponaro Andrea , Pian Phillip , Piskorowski Rebecca A. , Moroni Anna , Siegelbaum Steven A.
Published: March 2011

Hyperpolarization-activated cyclic nucleotide-regulated (HCN) channels in the brain associate with their auxiliary subunit TRIP8b (also known as PEX5R), a cytoplasmic protein expressed as a family of alternatively spliced isoforms. Recentin vitroandin vivostudies have shown that association of TRIP8b with HCN subunits both inhibits channel opening and alters channel membrane trafficking, with some splice variants increasing and others decreasing channel surface expression. Here, we address the structural bases of the regulatory interactions between mouse TRIP8b and HCN1. We find that HCN1 and TRIP8b interact at two distinct sites: an upstream site where the C-linker/cyclic nucleotide-binding domain of HCN1 interacts with an 80 aa domain in the conserved central core of TRIP8b; and a downstream site where the C-terminal SNL (Ser-Asn-Leu) tripeptide of the channel interacts with the tetratricopeptide repeat domain of TRIP8b. These two interaction sites play distinct functional roles in the effects of TRIP8b on HCN1 trafficking and gating. Binding at the upstream site is both necessary and sufficient for TRIP8b to inhibit channel opening. It is also sufficient to mediate the trafficking effects of those TRIP8b isoforms that downregulate channel surface expression, in combination with the trafficking motifs present in the N-terminal region of TRIP8b. In contrast, binding at the downstream interaction site serves to stabilize the C-terminal domain of TRIP8b, allowing for optimal interaction between HCN1 and TRIP8b as well as for proper assembly of the molecular complexes that mediate the effects of TRIP8b on HCN1 channel trafficking.
1-(3-[18F]fluoropropyl)piperazines as model compounds for the radiofluorination of pyrido[2,3-d]pyrimidines
Authors: Grosse-Gehling P. , Wuest F.R. , Peppel T. , Köckerling M. , Mamat C.
Published: March 2011

The visualization of cyclin-dependent kinases (CDKs), which are overexpressed in multiple tumor types, with radiolabeled CDK inhibitors by means of positron emission tomographyin vivois a promising approach for tumor imaging. Pyrido[2,3-d]pyrimidines belong to a class of inhibitors, which bind with high affinity to CDK4 and CDK6. 1-(3-[18F]Fluoropropyl)-4-(4-nitrophenyl)piperazine and 1-(3-[18F]fluoropropyl)-4-(6-nitropyridin-3-yl)piperazine represent structural elements of the appropriate CDK inhibitors and were therefore chosen as model compounds for the incorporation of fluorine-18 into pyrido[2,3-d]pyrimidines. Three methods are known for the preparation of tertiary 3-[18F]fluoropropyl-amines: 1) the direct substitution of a good leaving group, 2) the two-step reaction synthesizing a 3-[18F]fluoropropyl intermediate, and 3) the utilization of aziridinium or azetidinium salts. In general, radiofluorinations using azetidinium salts lead to excellent radiochemical yields in short periods of time. For these reasons, we developed a synthesis route to tosylated piperazine precursors and established a radiolabeling approach based on the incorporation of fluorine-18 into open-chained tosylates as well as the respective azetidinium spiro compounds to yield the desired radiofluorinated piperazines successfully.
Neptunium(V) sorption on kaolinite
Authors: Amayri S. , Jermolajev A. , Reich T.
Published: March 2011

The sorption behavior of neptunium(V) onto the clay mineral kaolinite was studied in batch experiments under different experimental conditions: [Np(V)]=7 × 10−12–8 × 10−6 M, solid-to-liquid ratio 2–20 g L−1, I=0.1 and 0.01 M NaClO4, pH=6–10, ambient air and Ar atmosphere. The short-lived isotope 239Np (T
1/2=2.36 d) was used instead of 237Np (T
1/2=2.14 × 106 a) to study the sorption behavior of Np(V) at environmentally-relevant concentrations, i.e., 7 × 1012 M Np. In addition, 239Np(V) served as tracer to measure sorption isotherms over six orders of magnitude in Np concentration (4.8 × 10−12–1.0 × 10−4 M). The results show that Np(V) sorption on kaolinite is strongly influenced by pH, CO2, and ionic strength. The sorption of 8 × 10−6 M Np(V) at pH 9.0, and ionic strength of 0.1 M NaClO4 was proportional to the solid-to-liquid ratio of kaolinite in the range of 2–10 g L−1. In the absence of CO2, the Np(V) uptake increased continuously with increasing pH value up to 97% at pH 10. Under ambient CO2, the sorption of Np decreased above pH 8 up to zero at pH 10. An increase of Np(V) concentration from 7 × 10−12 to 8 × 10−6 M resulted in a shift of the sorption pH edge by up to one pH unit to higher pH values. The ionic strength influenced the Np(V) sorption onto kaolinite only in the presence of ambient CO2. Under Ar atmosphere the sorption of Np(V) was independent from ionic strength, indicating the formation of inner-sphere complexes of Np(V) with kaolinite. Time-dependent batch experiments at pH 9.0 under ambient CO2 showed that the sorption of Np(V) on kaolinite is fast and fully reversible over six orders in Np(V) concentration.
Interference Effects in Vibronic 2D-Spectra of Diatomic Molecules
Authors: Schubert Alexander , Engel Volker
Published: March 2011

We theoretically study interference effects in two-dimensional (2D) vibronic spectra which arise from two electronically excited states taking part in the multi-photon process initiated by femtosecond laser pulses. Therefore, a model is employed which mimiques the situation encountered in many halogen and interhalogen molecules. There, upon excitation from the ground state, an excited bound state and a dissociative state exist which are close in energy. We demonstrate that the different pathways to final states which enter into the third-order polarization result in pronounced interference patterns in the 2D-spectra.
Circular Dichroism in Ion Yields in Multiphoton Ionization of (R)-Propylene Oxide Employing Femtosecond Laser Pulses
Authors: Horsch Philipp , Urbasch Gunter , Weitzel Karl-Michael
Published: March 2011

The feasibility of measuring circular dichroism (CD) in ion yields is demonstrated in multiphoton ionization employing femtosecond laser radiation for the first time. CD values for (R)-propylene oxide are reported at 738 nm, 810 nm and 878 nm. The data suggest the possibility of resonance contributions at 810 nm. At the other wavelengths the CD appears to originate from non-resonant multiphoton ionization. Possible implications of measuring non-resonant CD are discussed.
Intratumor Heterogeneity in Evolutionary Models of Tumor Progression
Authors: Durrett Rick , Foo Jasmine , Leder Kevin , Mayberry John , Michor Franziska
Published: March 2011

With rare exceptions, human tumors arise from single cells that have accumulated the necessary number and types of heritable alterations. Each such cell leads to dysregulated growth and eventually the formation of a tumor. Despite their monoclonal origin, at the time of diagnosis most tumors show a striking amount of intratumor heterogeneity in all measurable phenotypes; such heterogeneity has implications for diagnosis, treatment efficacy, and the identification of drug targets. An understanding of the extent and evolution of intratumor heterogeneity is therefore of direct clinical importance. In this article, we investigate the evolutionary dynamics of heterogeneity arising during exponential expansion of a tumor cell population, in which heritable alterations confer random fitness changes to cells. We obtain analytical estimates for the extent of heterogeneity and quantify the effects of system parameters on this tumor trait. Our work contributes to a mathematical understanding of intratumor heterogeneity and is also applicable to organisms like bacteria, agricultural pests, and other microbes.
Pulmonary Toxicity in Mice by 2‐ and 13‐week Inhalation Exposures to Indium‐tin Oxide and Indium Oxide Aerosols
Authors: Nagano Kasuke , Nishizawa Tomoshi , Eitaki Yoko , Ohnishi Makoto , Noguchi Tadashi , Arito Heihachiro , Fukushima Shoji
Published: March 2011

Pulmonary Toxicity in Mice by 2‐ and 13week Inhalation Exposures to Indium‐tin Oxide and Indium Oxide Aerosols: Kasuke Nagano, et al., Japan Bioassay Research Center, Japan Industrial Safety and Health Association—

Objectives

Inhalation toxicities of indium‐tin oxide (ITO) and indium oxide (IO) in mice were characterized in comparison with those previously reported in rats.

Methods

B6C3F 1 mice of both sexes were exposed by inhalation to ITO or IO aerosol for 6 h/day, 5 day/wk for 2 wk at 0, 0.1, 1, 10 or 100 mg/m3or 13 wk at 0, 0.1or 1 mg/m3.

Results

ITO and IO particles were deposited in the lung, mediastinal lymph node (MLN) and nasal‐associated lymphoid tissue. Alveolar proteinosis, iniltrations of alveolar macrophages and inlammatory cells and increased lung weight were induced by 2‐ and 13‐week exposures to ITO and IO, while alveolar epithelial hyperplasia occurred only in the 2‐week exposures. Thickened pleural wall, hyperplastic MLN, extra medullary hematopoiesis in the spleen and increased levels of erythrocyte parameters were induced by 13‐week exposure to ITO. The ITO‐ and IO‐induced pulmonary lesions were milder in mice than those previously reported in rats, and the ibrotic lesions were different between these two species. Indium levels in the lung and pooled blood were analyzed in the mice exposed to ITO and IO for 13 wk. In the 13‐week inhalation exposure of mice to ITO, alveolar proteinosis and significantly increased lung weight were induced at the same exposure concentration as the current threshold limit value for indium and its compounds.
Material cost and escalation clauses in Indian construction contracts
Authors: Maran Ramachandran , Rajendran Senthil , Kalidindi Satyanarayana
Published: March 2011

The construction industry has a major role in the development of the Indian economy. This industry consumes 40 to 50% of the national five-year plan outlay and contributes 20% of gross domestic product. Medium to large construction projects take over a year for completion and the cost of materials and labour often increase, which leads to major problems in administration of the contract. The objectives of the present study were to study (a) the escalation clauses presently used in construction contracts adopted by various government departments/agencies in India, (b) the adequacy of compensation paid to the contractor based on currently used escalation clauses in government contracts, and (c) how far cost escalation has an impact on the construction projects. Personal interviews and questionnaire surveys were conducted among the clients and contractors of major government organisations and the data were analysed. This study revealed that (a) the contractor is not adequately compensated based on the currently used escalation clauses in government contracts, (b) the wholesale price index currently used in the escalation formula of many contracts does not adequately reflect the escalation in costs in building construction projects, (c) a building cost index needs to be used for calculating escalation payment in the building contracts instead of wholesale price index, (d) an escalation clause should be included in the government contracts where the project duration is more than 6 months and (e) cost escalation affects the quality, delays project completion and causes dispute between clients and contractors.
Evaluation of the Modified Albee Arthroplasty for Femoral Head Loss Secondary to Septic Arthritis in Young Children
Authors: Li Xue-dong , Chen Bin , Luo Shao-wei , Ji Shi-jun , Du Shi-xin
Published: March 2011

BACKGROUND:

Surgical treatment options for femoral head deficiency in infants secondary to septic arthritis of the hip are varied and associated with uncertain long-term outcomes. The modified Albee arthroplasty has been considered an acceptable procedure; however, the long-term outcomes of this procedure have not been reported, to our knowledge. We evaluated the long-term outcomes of the modified Albee arthroplasty in young patients with severe sequelae of septic arthritis of the hip.

METHODS:

We retrospectively studied twenty-one children (twenty-one hips) in whom Choi type-IVB sequelae of septic arthritis of the hip had been treated with a modified Albee arthroplasty and six patients with the same sequelae who had been managed with simple observation. The Trendelenburg sign, pain, the range of motion, hip function, the Harris hip score, and limb-length discrepancy were assessed clinically. Remodeling of the femoral head, hip stability, and arthritic changes in the hip were evaluated radiographically.

RESULTS:

The twenty-one patients with the modified Albee arthroplasty were followed for an average of 121.2 ± 38.6 months and had better outcomes, in terms of the Trendelenburg sign, the Harris hip score, pain, the hip range of motion, and limb-length discrepancy, than the six patients who underwent simple observation. Patients who were two years of age or younger at the time of the arthroplasty exhibited a significantly less severe limb-length discrepancy and less loss of motion than those who were older than two at the time of the surgery. Furthermore, limb-length discrepancy was positively correlated and the range of motion of the hip and the Harris hip scores were negatively correlated with the patient's age at the time of the surgery, suggesting that early surgery in patients with severe sequelae of septic arthritis of the hip is associated with a better clinical outcome.

CONCLUSIONS:

The modified Albee arthroplasty is a feasible and clinically useful procedure for the treatment of severe sequelae of septic arthritis of the hip, particularly in children who are two years of age or younger.

LEVEL OF EVIDENCE:

Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence.

ORIGINAL ABSTRACT CITATION:

“Evaluation of the Modified Albee Arthroplasty for Femoral Head Loss Secondary to Septic Arthritis in Young Children” (2010;92:1370-80)
The Electoral System as a Factor in Striking a Balance between Governmental Stability and Representation
Authors: Yuval Fany
Published: March 2011

The relevant literature provides substantial empirical evident supporting the fact that the ability to govern weakens as the degree of representation increases. Democracies use various mechanisms to maintain the balance between stability and representation. Using simulation analysis, this work seeks to understand to what extent the various structures of electoral systems affect the level of governmental stability without excessively undermining the principle of representation. Can electoral systems be differentiated from one another, and which system is most advantageous? To clarify these questions, this work processed the actual results of the three last elections in Israel, for 2003-2009, using the format of various electoral systems. A comparative review of the simulations leads to the conclusion that a mixture of nationwide and regional elections, a small number of constituencies and the single-seat method will moderate the results, providing a better balance between the two democratic—the ability to rule and the degree of representation. The total representation (T.R.) system seems to be best for striking a reasonable balance between regional and national issues. It also offers a simple solution for resolving the disadvantage of majority systems in single-seat constituencies, the lack of representation for the losing votes in the constituencies. In the total representation system, the winners' votes are counted to determine the regional winner, while the losers' votes are totaled on the national party level and awarded proportional representation. This procedure makes the total representation system seem fairer than its competitors.
Serum Bilirubin Links UGT1A1*28 Polymorphism and Predicts Long-Term Cardiovascular Events and Mortality in Chronic Hemodialysis Patients
Authors: Chen Ying-Hwa , Hung Szu-Chun , Tarng Der-Cherng
Published: March 2011

Background and objectives

Bilirubin is a protective factor with antioxidant and anti-inflammatory properties, but its association with clinical outcomes of hemodialysis patients is unknown. Bilirubin degradation is mainly determined by the activity of hepatic bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1), which is significantly influenced by a TA-repeat polymorphism in the gene's promoter, an allele designated UGT1A1*28. The study aimed to clarify the association between serum bilirubin and UGT1A1*28 polymorphism and their respective effect on outcomes of chronic hemodialysis patients.

Design, setting, participants, & measurements

The cohort study comprised 661 chronic hemodialysis patients who were prospectively followed for 12 years. The endpoints were cardiovascular events (CVEs) and all-cause mortality.

Results

After adjustment for traditional and dialysis-related risk factors, individuals with bilirubin in the upper tertile had an adjusted hazard ratio of 0.32 for CVEs and 0.48 for all-cause mortality compared with those in the lower tertile. Individuals homozygous for UGT1A1*28 (genotype 7/7) had significantly higher bilirubin levels than those with 6/6 and 7/6 genotypes. In the same multivariable-adjusted model, individuals with 7/7 had approximately one tenth the risk for CVEs and one fourth the risk for all-cause mortality as compared with carriers of the 6 allele.

Conclusions

A graded, reverse association was noted between serum bilirubin and adverse outcomes among chronic hemodialysis patients. Moreover, the UGT1A1*28 polymorphism had strong effects on bilirubin levels and the 7/7 genotype might have an important effect on reducing CVEs and death.
Reduction in cisplatin genotoxicity (micronucleus formation) in non target cells of mice by protransfersome gel formulation used for management of cutaneous squamous cell carcinoma
Authors: Gupta Vandana , Agrawal Ramesh , Trivedi Piyush
Published: March 2011

Reduction in cisplatin genotoxicity (micronucleus formation) in non target cells of mice by protransfersome gel formulation used for management of cutaneous squamous cell carcinoma

Cisplatin-loaded protransfersome system was prepared and characterized forin vitrodrug permeation, drug deposition and antitumor effect. A histopathological study and a genotoxicity study were also done. The skin permeation data of cisplatin from protransfersome gel formulation revealed 494.33 ± 11.87 μg cm-2, which was significantly higher than that from the control plain drug solution in 0.9 % NaCl (p< 0.001). Untreated group of animals showed invasive moderately differentiated keratinizing squamous cell carcinoma (malignant stage). However, with cisplatin loaded protransfersome gel system simple epithelial hyperplasia (pre-cancerous stage) with no cancerous growth was observed. Also, a significant induction in micronucleus formation was found in the group that was treated with injectable intraperitoneal cisplatin preparation in 0.9 % saline as compared to the group treated with topical protransfersome gel formulation. The findings of this research work appear to support improved, site-specific and localized drug action in the skin, thus providing a better option for dealing with skin related problems like squamous cell carcinoma.
Development and evaluation of in situ novel intragastric controlled-release formulation of hydrochlorothiazide
Authors: Patel Ravikumar , Patel Jayvadan
Published: March 2011

Development and evaluation of in situ novel intragastric controlled-release formulation of hydrochlorothiazide

In situ forming intragastric controlled-release formulation is a new technology in the field of oral controlled-release delivery systems. The objective of this study was to develop formulations that can control drug release up to 24 hours. In addition, a combination of appropriate polymers and solvents was selected that could form a drug loaded gel at the process temperature of 60-70 °C, which gel could turn into a rigid mass upon exposure to dissolution fluid at body temperature. The drug release mechanism from this rigid mass was controlled by different formulation factors such as different polymer grades, polymer concentrations, hydrophobicity or hydrophilicity of solvents, different drug loadings, and physicochemical properties of additional excipients. After evaluating different formulation factors, Ethocel 10 FP and triethyl citrate were selected for further studies using hydrochlorothiazide as a model drug. Polynomial correlation between viscosity of the blank gel and drug release profile was also obtained.