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MicroRNA-223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells.
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MicroRNAs (miRNAs) are thought to modulate a variety of cellular events. Several studies have revealed the functions of miR-223 in granulopoiesis. Here we analysed miR-223 expression in various human tissues, blood and leukaemia cells, and focused on its role in K562 erythroid and megakaryocytic differentiation. MiR-223 was detected not only in granulocytes but also in erythroid cells. In K562 cells, expression of miR-223 was down-regulated during haemin-induced erythroid differentiation but up-regulated during phorbol myristate acetate (PMA)-induced megakaryocytic differentiation. The overexpression of miR-223 resulted in significant decrease of gamma-globin mRNA and the fraction of benzidine-positive cells in K562 cells, suggesting a suppressive effect of miR-223 on erythroid differentiation. Peaks corresponding to 4N cells in stable transfectants overexpressing miR-223 were higher than that in control K562 cells during megakaryocytic differentiation, indicating that miR-223 increases megakaryocytic differentiation. The expression of LIM domain only 2 (LMO2) reporter was suppressed in NIH-3T3 when the expression of miR-223 was enforced by both the luciferase and fluorescence system. Furthermore, LMO2 mRNA and protein levels were significantly decreased in stable K562 transfectants overexpressing miR-223. These results indicate that LMO2 is a direct target of miR-223. Thus, our results suggest that miR-223 reversibly regulates erythroid and megakaryocytic differentiation of K562 cells via down-modulation of LMO2.
| 19,017,354
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Iranian nurses' preparation for loss: finding a balance in end-of-life care.
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To explore the nurse-patient interaction in terminally ill situations in acute care, focusing on the nurses' preparation for loss. Caring for dying patients can be a distressing and sometimes even threatening experience for nurses. Despite the vast body of literature on nurse/patient interaction and the quality of end-of-life care, few studies focus specifically on nurses' experience. A grounded theory approach was used to explore nurses' interaction with dying patients and their families and examine how nurses deal with situations in which the patient's death is inevitable. Eighteen nurses were interviewed up to three times each at three teaching hospitals in Isfahan, Iran, during autumn 2006. A shortlist of possible participants was obtained by means of theoretical sampling and those who had experienced the death of patients and were able to express their feelings verbally were selected. The results clarified a core consideration: striking a balance between restorative and palliative care, information and hope, expectations and abilities and intimacy and distance. Attaining a balance in caring for dying patients is a major challenge to nurses: it concerns not only their interactions with patients and their families, but also their perceptions of themselves and their actions in end-of-life care. In end-of-life care, it is important for nurses to be able to change the focus of their care when the patient's condition is diagnosed as irreversible. They also need to be well equipped to maintain a balance, thereby preparing themselves for the patient's forthcoming death.
| 19,017,370
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Fast-growing pancreatic neuroendocrine carcinoma in a patient with multiple endocrine neoplasia type 1: a case report.
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Predictive genetic screening and regular screening programs in patients with multiple endocrine neoplasia type 1 are intended to detect and treat malignant tumors at the earliest stage possible. Malignant neuroendocrine pancreatic tumors are the most frequent cause of death in these patients. However, the extent and intervals of screening in patients with multiple endocrine neoplasia type 1 are controversial as neuroendocrine tumors are usually slow growing. Here we report the case of a patient who developed a fast-growing neuroendocrine carcinoma within 15 months of a laparoscopic distal pancreatic resection. We followed a group of 45 patients with multiple endocrine neoplasia type 1 by an annual screening program in the Department of Visceral, Thoracic, and Vascular Surgery at the University Hospital Marburg in cooperation with the Department of Radiology and the Division of Endocrinology. A man with multiple endocrine neoplasia type 1 who was diagnosed with a recurrent primary hyperparathyroidism underwent a distal pancreatic resection for a non-functional neuroendocrine tumor. In the context of our regular screening program, a large non-functional neuroendocrine tumor was diagnosed in the pancreatic head 15 months after the first pancreatic surgery. Therefore, we performed an enucleation and regional lymph node resection. At histology, the diagnosis of a neuroendocrine carcinoma with one lymph node metastasis was established. There was no evidence of recurrence 9 months after re-operation. Fast-growing neuroendocrine tumors are rare in patients with multiple endocrine neoplasia type 1. The intervals, both postoperative and in newly diagnosed pancreatic lesions, in patients with multiple endocrine neoplasia type 1 should be reduced to 6 months to establish the early diagnosis of rapidly progressive disease in a small subset of patients.
| 19,017,391
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Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial.
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Previous findings suggest that a delayed administration of phenylephrine replacing norepinephrine in septic shock patients causes a more pronounced hepatosplanchnic vasoconstriction as compared with norepinephrine. Nevertheless, a direct comparison between the two study drugs has not yet been performed. The aim of the present study was, therefore, to investigate the effects of a first-line therapy with either phenylephrine or norepinephrine on systemic and regional hemodynamics in patients with septic shock. We performed a prospective, randomized, controlled trial in a multidisciplinary intensive care unit in a university hospital. We enrolled septic shock patients (n = 32) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomly allocated to treatment with either norepinephrine or phenylephrine infusion (n = 16 each) titrated to achieve a mean arterial pressure between 65 and 75 mmHg. Data from right heart catheterization, a thermodye dilution catheter, gastric tonometry, acid-base homeostasis, as well as creatinine clearance and cardiac troponin were obtained at baseline and after 12 hours. Differences within and between groups were analyzed using a two-way analysis of variance for repeated measurements with group and time as factors. Time-independent variables were compared with one-way analysis of variance. No differences were found in any of the investigated parameters. The present study suggests there are no differences in terms of cardiopulmonary performance, global oxygen transport, and regional hemodynamics when phenylephrine was administered instead of norepinephrine in the initial hemodynamic support of septic shock. ClinicalTrial.gov NCT00639015.
| 19,017,409
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Walking the dog: exploration of the contact networks between dogs in a community.
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This study uses social network analysis to investigate potential contact among 214 dog-owning households in a UK community through their utilization of public space during walking. We identified a high level of potential contact between dog-owning households; most households walked their dogs in only a few areas but a small number visited many. Highly connected households were more likely to have multiple dogs, walk their dogs off lead, and own Working, Pastoral or some Terrier types. Similarly, most areas were only visited by a few households but a few were visited by many. Despite identification of subgroups of households and locations, we demonstrated high connectivity between dog-owning households, with minimum path lengths of two 'steps' (household-area-household, 74%) or four 'steps' (via two areas, 26%).
| 19,017,431
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Evaluation of new GenoType MTBDRplus for detection of resistance in cultures and direct specimens of Mycobacterium tuberculosis.
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Molecular methods frequently used in laboratories can now give us useful information about low growth bacteria. To evaluate the new GenoType MTBDRplus assay for its ability to detect mutations in the 81-bp hotspot region of the rpoB gene, mutations in codon 315 of the katG gene and alterations in the inhA promoter region. Prospective resistance to rifampicin (RMP) and isoniazid (INH) study using Mycobacterium tuberculosis positive specimens and cultures comparing the results of GenoType MTBDRplus with those obtained phenotypically with the Bactec MGIT (Mycobacterial Growth Indicator Tube) 960. In 59 specimens (18 smear microscopy samples and 41 solid and liquid medium cultures), mutations were detected in all of 36 M. tuberculosis strains phenotypically resistant to RMP (100%), and in 35 of 37 strains phenotypically resistant to INH (94.59%). The new assay prompted a 21.6% increase in the direct detection of INH resistance in the strains studied, due to the incorporation of inhA promoter region probes in the test. The GenoType MTBDRplus assay is a valid method for detecting the most common mutations in strains resistant to RMP and INH. However, further phenotypic testing is required, as the assay failed to detect 100% of INH and RMP resistance.
| 19,017,457
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Pluronic/chitosan shell cross-linked nanocapsules encapsulating magnetic nanoparticles.
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We have developed novel Pluronic/chitosan nanocapsules encapsulating iron oxide nanoparticles. These nanocapsules were produced by dispersing hydrophobically-modified iron oxide nanoparticles and amine-reactive Pluronic derivatives in an organic solvent, and subsequently emulsification in an aqueous chitosan solution by ultrasonication. The resultant shell cross-linked nanocapsules had a unique core/shell type nanoreservoir architecture: an inner core encapsulating magnetic nanoparticles and a hydrophilic Pluronic/chitosan polymer shell layer, as confirmed by thermogravimetric analysis and transmission electron microscopy. Confocal laser scanning microscopy revealed that the rhodamine-labeled nanocapsules were efficiently internalized by human lung carcinoma cells upon exposure to an external magnetic field. The present study suggested that these novel nanomaterials could be dually utilized for the magnetically-triggered delivery of various anti-cancer agents and for cancer diagnosis with magnetic resonance imaging.
| 19,017,471
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Induction of Mac-2BP by nerve growth factor is regulated by the PI3K/Akt/NF-kappaB-dependent pathway in the HEK293 cell line.
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Mac-2BP is a ligand of the galectin family that has been suggested to affect tumor proliferation and metastasis formation. We assessed Mac-2BP expression at the transcriptional and translational levels to evaluate nerve growth factor (NGF)-induced Mac-2BP expression. A time kinetic analysis using reverse transcription-polymerase chain reaction showed that NGF-induced Mac-2BP transcript levels were 4-5 times higher than in controls. Mac-2BP enzyme-linked immunosorbent assay and immunofluorescence staining showed a 2-3-fold increase in intracellular and secreted Mac-2BP as a result of NGF stimulation. This increase was regulated by Akt activation and NF-kappaB binding. p65 and p50-NF-kappaB are major transcriptional factors in the Mac-2BP promoter region, and were shown to be regulated in accordance with the Akt activation states. Collectively, these results suggest that NGF induces Mac-2BP expression via the PI3K/Akt/NF-kappaB pathway.
| 19,017,490
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Accidents and injuries in people with epilepsy attending a tertiary care center in India.
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People with epilepsy have a higher risk of accidents and injuries when compared to others in the community. Seizure frequency and other characteristics of epilepsy and its treatment are known to influence this risk. The risk of accidental injury to people with epilepsy may vary in different geographical areas, according to their life style, leisure activities and other pursuits. The objective was to ascertain the accidents and injuries experienced by a cohort of people with epilepsy in India, and to ascertain any possible predictors. The study was carried out in the Epilepsy Clinic of Sree Chitra Tirunal Institute for Medical Sciences and Technology between January and June 2007. Using a structured questionnaire, we interviewed all consenting adults attending this tertiary epilepsy center who had had active epilepsy for one or more years. Two hundred and fifty five patients completed the study. The diagnoses included localization-related epilepsy for 62.6% of the patients and generalized epilepsy for the remainder. During the 12 months prior to the interview, 44.8% had had at least one injury; 7.8% had sustained an accident. Road traffic accidents (3.1%), burns (2.5%), electric shocks (0.8%) and near drowning (0.4%) were the commonly reported accidents. Age, sex, type of epilepsy and type of medication had no significant association with the occurrence of injuries or accidents. However, we found that a quarter of the people with epilepsy studied had experienced serious injuries.
| 19,017,569
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Psychosocial impact of epilepsy in women of childbearing age in India.
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The aim was to evaluate comprehensively the psychosocial impact of epilepsy in women between 15-40 years of age with epilepsy, compared to those with migraine and healthy, pregnant women. One hundred women with epilepsy, 50 with migraine and 100 healthy, pregnant women were enrolled over a two-year period. The three groups were assessed using questionnaires for quality of life (QOL), coping strategies and caregiver burden. The influence of demographic and seizure variables on these psychosocial outcomes were also assessed.It was found that quality of life was least, and the burden experienced by the caregiver was significantly more in patients with epilepsy (p < 0.001). Women with epilepsy relied more on religion/faith as a coping method (p = 0.021), and less on problem solving strategies (p < 0.001) when compared to those with migraine. When compared to healthy, pregnant women, they more frequently employed religious methods of coping and denial (p < 0.001), with significantly less use of problem solving techniques, acceptance, and positive and negative distraction(p < 0.001). Less frequent seizures, better education and remission sustained for at least six months, were associated with better QOL. Educational status, frequency of seizures and time elapsed since last seizure emerged as significant determinants of coping behaviour. Low educational status and monthly income of the family contributed significantly to caregiver burden.This study helped to identify the different areas of psychosocial impairment in patients with epilepsy, as well as the contributing factors. Women with epilepsy rarely used constructive coping strategies, and this was found to contribute to their poor psychosocial status and adjustment within the family and society at large.
| 19,017,570
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Rasmussen's encephalitis and Behcet's disease: autoimmune disorders in first degree relatives.
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We report a patient with adolescent-onset, Rasmussen's encephalitis, presenting with intractable focal seizures, mild hemiparesis, cognitive impairment, dystonia, and severe hemiballism. His father had Behcet's disease, considered to be an autoimmune disorder. Recent reports have directly implicated the role of cytotoxic T lymphocytes in the pathogenesis of both Rasmussen's encephalitis and Behcet's disease. The occurrence of Behcet's disease and Rasmussen's encephalitis in the same family suggests involvement of common genetic factors such as HLA haplotypes in both autoimmune disorders. It is possible that members of this family are genetically susceptible to developing autoimmune conditions that have been precipitated by separate environmental triggers.
| 19,017,575
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Motivational enhancement therapy with and without cognitive behavior therapy to treat type 1 diabetes: a randomized trial.
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Although psychological issues can interfere with diabetes care, the effectiveness of psychological treatments in improving diabetes outcomes is uncertain. To determine whether motivational enhancement therapy with or without cognitive behavior therapy improves glycemic control in type 1 diabetes compared with usual care. Randomized, controlled trial. 8 diabetes centers in London and Manchester, United Kingdom. 344 adults with type 1 diabetes for longer than 2 years, with hemoglobin A(1c) levels of 8.2% to 15%, and without complications or severe comorbid disease. Nurse-delivered motivational enhancement therapy (4 sessions over 2 months), motivational enhancement therapy plus cognitive behavior therapy (12 sessions over 6 months), or usual care. 12-month change in hemoglobin A(1c) levels (primary outcome), hypoglycemic events, depression, quality of life, fear of hypoglycemia, diabetes self-care activities, and body mass index (secondary outcomes). In an analysis including all randomly assigned patients, the 12-month change in hemoglobin A(1c) levels compared with usual care was -0.46% (95% CI, -0.81% to -0.11%) in the motivational enhancement therapy plus cognitive behavior therapy group and -0.19% (CI, -0.53% to 0.16%) in the motivational enhancement therapy group alone. There was no evidence of treatment effects on secondary outcomes. Of 1659 screened patients, only 507 were eligible and 344 participated. Data on the primary outcome were unavailable for 11.3% of the participants. Study design did not permit distinction of the additive effect of cognitive behavior therapy plus motivational enhancement therapy from the effect of greater intensity and duration of the combined intervention compared with the motivational enhancement therapy alone. Nurse-delivered motivational enhancement therapy and cognitive behavior therapy is feasible for adults with poorly controlled type 1 diabetes. Combined therapy results in modest 12-month improvement in hemoglobin A(1c) levels compared with usual care, but motivational enhancement therapy alone does not.
| 19,017,589
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Healing skills for medical practice.
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It is well recognized that physicians' relationships with their patients can have healing effects, but the skills in this area of medical practice are understudied. This article reports on research designed to identify a core set of healing skills. The authors interviewed 50 practitioners, who were identified by their peers as "healers," representing both allopathic and complementary medicine and alternative medicine. Interviews were tape-recorded, transcribed, made anonymous, and analyzed independently, and differences were reconciled by discussion. Eight skills emerged as pivotal from the transcripts of these interviews: do the little things; take time; be open and listen; find something to like, to love; remove barriers; let the patient explain; share authority; and be committed. Mastery of these skills would provide enduring improvements in patient care and reaffirm medicine's calling as a healing profession.
| 19,017,590
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Co-stimulation of the bone-related Runx2 P1 promoter in mesenchymal cells by SP1 and ETS transcription factors at polymorphic purine-rich DNA sequences (Y-repeats).
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Transcriptional control of Runx2 gene expression through two alternative promoters (P1 and P2) is critical for the execution of its function as an osteogenic cell fate determining factor. In all vertebrates examined to date, the bone related P1 promoter contains a purine-rich region (-303 to -128 bp in the rat) that separates two regulatory domains. The length of this region differs dramatically between species even within the same order. Using deletion analysis, we show that part of this purine-rich region (-200 to -128) containing a duplicated element (Y-repeat) positively regulates Runx2 P1 transcription. Electrophoretic mobility assays and chromatin immunoprecipitations reveal that Y-repeat binds at least two different classes of transcription factors related to GC box binding proteins (e.g. SP1 and SP7/Osterix) and ETS-like factors (e.g. ETS1 and ELK1). Forced expression of SP1 increases Runx2 P1 promoter activity through the Y-repeats, and small interfering RNA depletion of SP1 decreases Runx2 expression. Similarly, exogenous expression of wild type ELK1, but not a defective mutant that cannot be phosphorylated, enhances Runx2 gene expression. SP1 is most abundant in proliferating cells, and ELK1 is most abundant in postconfluent cells; during MC3T3-E1 osteoblast differentiation, both proteins are transiently co-expressed when Runx2 expression is enhanced. Taken together, our data suggest that basal Runx2 gene transcription is regulated by dynamic interactions between SP1 and ETS-like factors during progression of osteogenesis.
| 19,017,640
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Interaction of Tim23 with Tim50 Is essential for protein translocation by the mitochondrial TIM23 complex.
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The TIM23 complex is the major translocase of the mitochondrial inner membrane responsible for the import of essentially all matrix proteins and a number of inner membrane proteins. Tim23 and Tim50, two essential proteins of the complex, expose conserved domains into the intermembrane space that interact with each other. Here, we describe in vitro reconstitution of this interaction using recombinantly expressed and purified intermembrane space domains of Tim50 and Tim23. We established two independent methods, chemical cross-linking and surface plasmon resonance, to track their interaction. In addition, we identified mutations in Tim23 that abolish its interaction with Tim50 in vitro. These mutations also destabilized the interaction between the two proteins in vivo, leading to defective import of preproteins via the TIM23 complex and to cell death at higher temperatures. This is the first study to describe the reconstitution of the Tim50-Tim23 interaction in vitro and to identify specific residues of Tim23 that are vital for the interaction with Tim50.
| 19,017,642
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Bag of Peaks: interpretation of NMR spectrometry.
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The analysis of high-resolution proton nuclear magnetic resonance (NMR) spectrometry can assist human experts to implicate metabolites expressed by diseased biofluids. Here, we explore an intermediate representation, between spectral trace and classifier, able to furnish a communicative interface between expert and machine. This representation permits equivalent, or better, classification accuracies than either principal component analysis (PCA) or multi-dimensional scaling (MDS). In the training phase, the peaks in each trace are detected and clustered in order to compile a common dictionary, which could be visualized and adjusted by an expert. The dictionary is used to characterize each trace with a fixed-length feature vector, termed Bag of Peaks, ready to be classified with classical supervised methods. Our small-scale study, concerning Type I diabetes in Sardinian children, provides a preliminary indication of the effectiveness of the Bag of Peaks approach over standard PCA and MDS. Consistently, higher classification accuracies are obtained once a sufficient number of peaks (>10) are included in the dictionary. A large-scale simulation of noisy spectra further confirms this advantage. Finally, suggestions for metabolite-peak loci that may be implicated in the disease are obtained by applying standard feature selection techniques.
| 19,017,658
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Sclerosing spindle cell rhabdomyosarcoma in an adult: report of a new case and review of the literature.
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Sclerosing spindle cell rhabdomyosarcoma (SSRMS) is a newly recognized entity in adults. The authors report a new case of SSRMS in a 31-year-old woman who presented with a large right leg mass. Biopsy revealed a malignant spindle cell neoplasm with focal sclerotic areas. A diagnosis of monophasic synovial sarcoma was favored initially. The tumor cells in the resection specimen were positive for myosin, myogenin, and MyoD1. Fluorescence in situ hybridization performed on the resection specimen showed no evidence of SYT gene rearrangement in the neoplastic cells, ruling out monophasic synovial sarcoma. A diagnosis of SSRMS was established. The patient succumbed to widely metastatic disease 16 months after initial diagnosis. This case highlights the utility of skeletal muscle markers and cytogenetic testing in distinguishing SSRMS from its mimic, monophasic synovial sarcoma. It is hoped that this case will expand the literature on adult SSRMS and help clinicians and pathologists better understand this newly described entity.
| 19,017,660
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APOE genotype and functional outcome following aneurysmal subarachnoid hemorrhage.
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Apolipoprotein E (apoE), the major apolipoprotein in the central nervous system, has been shown to influence neurologic disease progression and response to neurologic injury in a gene-specific manner. Presence of the APOE4 allele is associated with poorer response to traumatic brain injury and ischemic stroke, but the association between APOE genotype and outcome following aneurysmal subarachnoid hemorrhage (SAH) remains unclear. The purpose of this project was to investigate the association between APOE genotype and outcome after SAH. We also explored the association of APOE4 genotype and cerebral vasospasm (CV) presence in a subsample of our population with available angiographic data. A sample of 206 aneurysmal SAH participants had APOE genotyping performed, Glasgow outcome scores (GOS) and modified Rankin scores (MRS) collected at 3 and 6 months after aneurysm rupture. No significant association was found between the presence of the APOE4 genotype and functional outcomes controlling for age, race, size of hemorrhage (Fisher grade), and severity of injury (Hunt & Hess grade). However when controlling for CV and the covariates listed above, individuals with the APOE4 allele had worse functional outcomes at both time points. The presence of the APOE2 allele was not associated with functional outcomes even when considering presence of CV. There was no difference in mortality associated with APOE4 presence, APOE2 presence, or presence of CV. These findings suggest APOE4 allele is associated with poor outcome after aneurysmal SAH.
| 19,017,669
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Plasma total antioxidant activity in comparison with plasma NO and VEGF levels in patients with metabolic syndrome.
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The aim of our study was to estimate plasma antioxidant activity as well as plasma nitric oxide (NO) and vascular endothelial growth factor levels in patients with metabolic syndrome compared with healthy participants. Fifty patients (24 women and 26 men, mean age 55.9 + 11.8 years) with metabolic syndrome were compared with 25 healthy participants (12 women and 13 men, mean age 54.2 + 12.8 years). Plasma total antioxidant activity and plasma levels of NO and VEGF were determined in all participants. In the patients with metabolic syndrome, plasma total antioxidant activity, nitric oxide, and vascular endothelial growth factor were significantly lower (P < .001) than that observed in healthy participants (3.2 + 1.6 vs 6.4 + 2.1 mM/L), (6.3 + 2.2 vs 9.8 + 2.7 muM/L), and 71.0 + 16.9 vs 137.5 + 12.6 pg/mL), respectively. Decreased plasma total antioxidant activity, NO, and VEGF levels in patients with metabolic syndrome reflect significant endothelial dysfunction. This suggests that oxidation-reduction balance disorders might play an important role in this process.
| 19,017,672
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The physiological effects of short-term smoking cessation in claudicants.
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Smoking contributes to atherosclerosis and causes significant postoperative morbidity. New antismoking law forces short-term pre-operative abstinence. Demonstrable clinical benefit might motivate complete cessation. Our aim was to determine the effects of 24-hr smoking cessation on cardiorespiratory function and claudication distance. Smoking claudicants were randomized to 24hr smoking or abstinence. Following these separate periods, cardiopulmonary exercise testing was performed. Pre- and post-exercise, serum lactate and ankle brachial pressure index (ABPI) were measured. During exercise, cardiorespiratory function, initial and absolute claudication (IC,AC) distances and visual analogue scores (VAS) of pain were recorded. 16 patients completed both tests. IC, AC and VAS were unchanged with abstinence (P = .43, .66, .96, .83). ABPI drop post-exercise was unchanged with abstinence (P = .08, .09). Cardiorespiratory function was not affected by smoking cessation. Cardiorespiratory function and claudication symptoms are unchanged following 24-hr smoking cessation. No deterioration in respiratory function is important when considering anaesthetic administration. However, lack of symptomatic improvement may discourage patients from abstaining. Further investigation should determine correlation between short-term abstinence and postoperative morbidity.
| 19,017,673
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Do reimbursement delays discourage Medicaid participation by physicians?
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Policymakers have focused primarily on increasing Medicaid reimbursement rates to increase physicians' participation in Medicaid, although physicians often complain of payment delays and other administrative burdens associated with Medicaid. Linking state-level data on average reimbursement times to the 2004-05 Community Tracking Study Physician Survey, this study examines how Medicaid reimbursement time affects physicians' willingness to accept Medicaid patients. Delays in reimbursement can offset the effects of high Medicaid fees, thereby lowering participation to levels that are closer to those in states with relatively low rates. Increasing these rates may be insufficient to increase physicians' participation unless accompanied by reductions in administrative burden.
| 19,017,679
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The effect of pain on sickness absence among middle-aged municipal employees.
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To study the effects of pain on sickness absence, taking into account physical and psychosocial work load and socio-economic position. Data consisted of City of Helsinki personnel register data on sickness absence and a cross-sectional questionnaire survey which was carried out among employees of the City of Helsinki who reached the age of 40, 45, 50, 55 or 60 years during the years 2000-2002 (n = 8960, response rate 67%). Data sets were combined for those who gave permission for such linkage (78%). The main statistical method was negative binomial regression analysis. The burden of pain on sickness absence was dependent on the duration of absence: the longer the duration, the higher the burden. Self-certified absence was equally predicted by acute and chronic pain, but medically certified absence was more clearly predicted by chronic pain. Adjustments for a range of work load factors and socio-economic position showed that pain was a relatively independent determinant of subsequent sickness absence, but in particular physical work load and socio-economic position explained a small proportion of the association. Overall, pain accounted for 13% of self-certified absence among women and 8% among men. Corresponding figures were 23% and 25% for medically certified 4-14-day sickness absence and 37% and 30% for absence of over 2 weeks. The burden of pain on medically certified sickness absence is considerable. Prevention of pain problems is vital for reducing sickness absence rates.
| 19,017,703
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Risk-adapted stratification and treatment of childhood acute lymphoblastic leukaemia.
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Systematic enrollment of children and adolescents with acute lymphoblastic leukaemia (ALL) into clinical trials has allowed the establishment of prognostic parameters derived from initial diagnostic findings. More important, these trials have significantly contributed to the reduction of disease recurrence as much as to the reduction of acute and late side effects. Some problems that are related to the specificity of the parameters used for risk assessment were not overcome: high tumour load by white blood cell count (WBC), age and (rare) cytogenetic subtypes (e.g. t9;22) may characterise a significant proportion of children and adolescents with high-risk ALL. Most patients who will eventually relapse do not present with characteristic features at initial diagnosis. It appears feasible through careful response assessment to identify these patients at risk of relapse, who present initially without specific features. Earlier trials of the ALL-BFM (Berlin/Frankfurt/Münster) study group and others have demonstrated that inadequate leukaemic blast reduction in the peripheral blood or bone marrow after the first few days of therapy is highly predictive of treatment failure. Using clone-specific polymerase chain reaction-based detection of minimal residual disease (MRD) as done in trial AIEOP-BFM ALL 2000 allowed a close surveillance of specific treatment elements when applied in MRD positive patients. This may facilitate innovative chemotherapy approaches and a more rational use of allogeneic haematopoetic stem cell transplantation. In addition, genetic signatures of treatment response or failure have been identified.
| 19,017,727
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The differential effect of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women: relationship with the metabolic status.
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The wide family of the phytoestrogens has become an alternative to the classical hormonal therapy in menopause; nevertheless, some findings are still conflicting. To examine the effect of genistein administration on metabolic parameters and vascular reactivity considering the basal endocrine status of the patients. A randomized placebo controlled study was conducted at a university hospital. Fifty postmenopausal women participated. Thirty subjects (group A) were randomized to receive 54 mg/d genistein while 20 subjects (group B) were treated with the placebo for 24 wk. In group A, we distinguish two subgroups: 14 normoinsulinemic and 12 hyperinsulinemic patients. Anthropometric measures, hormonal and lipid assays, oral glucose tolerance test with glycemic, insulin, and C-peptide evaluation, indexes of insulin sensitivity and endothelial function, and euglycemic-hyperinsulinemic clamps were performed. The insulin basal values significantly decreased in group A, whereas the homeostasis model index of insulin sensitivity and the fasting glucose levels significantly improved compared with placebo group. The genistein administration decreased fasting glucose and area under the curve glucose levels in the normoinsulinemic patients after treatment. In the hyperinsulinemic patients, a significant reduction in fasting insulin, fasting C-peptide, and area under the curve insulin levels as well as an increase in fractional hepatic insulin extraction was shown. In these patients, high-density lipoprotein cholesterol levels were significantly improved. The endothelium-dependent and -independent dilatation improved in the treated group. Normoinsulinemic patients showed both a significantly enhanced flow-mediated and nitrate-mediated dilatation, whereas no significant changes were found in the hyperinsulinemic group. The glycoinsulinemic metabolism and the endothelial function were significantly influenced by genistein. In particular, normoinsulinemic patients showed an improvement in glycemic and vascular reactivity indexes. Conversely, an improvement in the insulin sensitivity indexes was noted in hyperinsulinemic patients.
| 19,017,760
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Differentiation between dementia and depression among older persons: can the difference between actual and premorbid intelligence be useful?
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We wanted to investigate whether the difference between actual and premorbid intelligence can be useful to make an early differentiation between Alzheimer's disease (AD) and depression among elderly. A Dutch version of the National Adult Reading Test (NLV), a measure of premorbid IQ and the Raven Coloured Progressive Matrices (RCPM), a measure of actual intelligence were administered to patients with mild (34) and moderate (27) AD, depressed elderly (36) and healthy control subjects (51). Logistic regression analyses revealed that intellectual decline (i.e. subtracting NLV percentile score from RCPM percentile score) was only able to predict group membership when moderate AD patients were compared to depressed and healthy individuals. Our results indicate that intellectual decline may not be a concomitant of elderly depression. However, the differentiation between mild AD and elderly depression can not be made by means of the difference between premorbid (NLV) and actual (RCPM) intelligence scores.
| 19,017,781
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Sortase A localizes to distinct foci on the Streptococcus pyogenes membrane.
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Cell wall peptidoglycan-anchored surface proteins are essential virulence factors in many gram-positive bacteria. The attachment of these proteins to the peptidoglycan is achieved through a transpeptidation reaction, whereby sortase cleaves a conserved C-terminal LPXTG motif and covalently attaches the protein to the peptidoglycan precursor lipid II. It is unclear how the sorting reaction is regulated spatially and what part sortase localization plays in determining the distribution of surface proteins. This is mainly the result of inadequate immunofluorescence techniques required to resolve these issues in certain bacterial pathogens. Here we describe the utilization of the phage lysin PlyC to permeabilize the cell wall of Streptococcus pyogenes to antibodies, thereby allowing the localization of sortase A using deconvolution immunofluorescence microscopy. We find that sortase localizes within distinct membranal foci, the majority of which are associated with the division septum and colocalize with areas of active M protein anchoring. Sortase distribution to the new septum begins at a very early stage, culminates during septation, and decays after division is completed. This implies that the sorting reaction is a dynamic, highly regulated process, intimately associated with cell division. The ability to study cytoplasmic and membrane antigens using deconvolution immunofluorescence microscopy will facilitate further study of cellular processes in S. pyogenes.
| 19,017,791
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Depression in primary care: three key challenges.
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The recognition and treatment of depression is a challenging area of clinical practice, especially in primary care where there are many patients with various presentations and a multitude of causes for distress. The prevalence of depression is increasing, and it is predicted to become second only to ischaemic heart disease as a cause of morbidity worldwide. Fortunately, the research evidence on effective approaches is increasing. This article looks at how we can best identify, treat and understand the perspectives of people with depression who are seen in primary care. Simple questionnaires can provide effective screening in generalist settings, particularly when targeting high-risk groups such as those with cardiovascular comorbidity or recurrent unexplained symptoms. Guidelines now exist for use of antidepressants and cognitive behavioural therapy for mild to moderate depression, although the latter needs effective policy implementation in clinical practice to maximise its impact for patients. However, there is also consistent evidence from service users that people with depression want individualised care which takes into account their preferences and concerns, even if this entails departure from guidelines. Adherence to treatment is low in many studies, and remodelling of services can easily lead to gaps in consistent approaches to personal care. The research challenges for the future include clarification of which patient groups merit proactive screening, how to enhance adherence, and the relative merits and outcomes of pharmacological versus behavioural therapies. Changes in policy and service configuration can improve or destabilise effective care, but high-quality and flexible intervention with patients with mild to moderate depression is likely to be cost-effective in view of the high prevalence and disease burden of this distressing problem.
| 19,017,840
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Application of cantharidin and podophyllotoxin for the treatment of plantar warts.
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A variety of treatment modalities have been described for cutaneous warts. We sought to determine the safety and efficacy of a topical formulation of cantharidin, podophyllotoxin, and salicylic acid in the treatment of plantar warts. This combination treatment is widely used in Europe and elsewhere but has not been described in the podiatric medical literature. A retrospective study was conducted of 144 patients with simple or mosaic plantar warts who were treated with a topical, pharmacy-compounded solution of cantharidin, 1%; podophyllotoxin, 5%; and salicylic acid, 30%. All of the patients, aged 8 to 52 years (mean +/- SD, 20.9+/-11.0 years), were treated according to the authors' standard protocol. Of the 144 patients, 92 were being treated for the first time. None of the 52 previously treated patients had received more than one other type of treatment in the past. After 6 months of follow-up, complete eradication of the plantar warts was noted in 138 of the 144 patients (95.8%). Of these patients, 125 (86.8%) required a single application of the solution, and 13 (9.0%) needed two or more applications. No significant adverse effects or complications were observed. A topical solution of cantharidin, podophyllotoxin, and salicylic acid was found to be safe and effective in the treatment of simple and mosaic plantar warts. This formulation is a promising alternative treatment modality for plantar warts.
| 19,017,852
|
Serum albumin concentration and waiting list mortality in idiopathic interstitial pneumonia.
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Hypoalbuminemia is a reliable predictor of mortality in patients with various illnesses as well as a predictor of disability and mortality in healthy older adults. The association between hypoalbuminemia and mortality in patients with idiopathic interstitial pneumonia remains unknown. The objective of this study was to examine the relationship between serum albumin concentration and mortality in a large cohort of patients with idiopathic interstitial pneumonia listed for lung transplantation. In patients classified as having idiopathic pulmonary fibrosis who were listed for lung transplantation with the United Network for Organ Sharing between January 1, 2004, and December 31, 2006 (n = 1,269), we studied the relationship between serum albumin concentration at the time of listing and mortality while awaiting transplantation. Lower serum albumin was associated with increased mortality rate. Patients with lower categories of serum albumin had increased mortality rates before and after multivariable adjustment (p value for linear trend < 0.0001). Analysis with serum albumin as a continuous predictor indicated that the mortality rate increased by 54% with each 0.5 g/dL decrease in serum albumin concentration (95% confidence interval, 32 to 79%). Lower serum albumin is strongly and independently associated with higher mortality in patients with idiopathic interstitial pneumonia on transplant waiting lists.
| 19,017,875
|
Relapsing polychondritis and airway involvement.
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To assess the prevalence and characteristics of airway involvement in relapsing polychondritis (RP). Retrospective chart review and data analysis of RP patients seen in the Rheumatology Clinic and the Complex Airway Center at Beth Israel Deaconess Medical Center from January 2004 through February 2008. RP was diagnosed in 145 patients. Thirty-one patients had airway involvement, a prevalence of 21%. Twenty-two patients were women (70%), and they were between 11 and 61 years of age (median age, 42 years) at the time of first symptoms. Airway symptoms were the first manifestation of disease in 17 patients (54%). Dyspnea was the most common symptom in 20 patients (64%), followed by cough, stridor, and hoarseness. Airway problems included the following: subglottic stenosis (n = 8; 26%); focal and diffuse malacia (n = 15; 48%); and focal stenosis in different areas of the bronchial tree in the rest of the patients. Twelve patients (40%) required and underwent intervention including balloon dilatation, stent placement, tracheotomy, or a combination of the above with good success. The majority of patients experienced improvement in airway symptoms after intervention. One patient died during the follow-up period from the progression of airway disease. The rest of the patients continue to undergo periodic evaluation and intervention. In this largest cohort described in the English language literature, we found symptomatic airway involvement in RP to be common and at times severe. The nature of airway problems is diverse, with tracheomalacia being the most common. Airway intervention is frequently required and in experienced hands results in symptom improvement.
| 19,017,885
|
Elevated levels of the receptor for advanced glycation end products, a marker of alveolar epithelial type I cell injury, predict impaired alveolar fluid clearance in isolated perfused human lungs.
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Although alveolar epithelial injury is a major determinant of outcome in patients with acute lung injury, there is no reliable biological marker of alveolar epithelial injury. The primary objective was to determine whether elevated levels of the receptor for advanced glycation end products (RAGE), a marker of alveolar epithelial injury, reflect impaired alveolar fluid clearance (AFC) in an ex vivo perfused human lung preparation. A second objective was to determine whether levels of a marker of endothelial injury, von Willebrand factor antigen (vWF:Ag), are associated with impaired AFC. Human lungs (N = 30) declined for transplantation by the California Transplant Donor Network were perfused at a constant pulmonary artery pressure of 12 mm Hg. Following rewarming to 36 degrees C, the lungs were inflated with a continuous positive airway pressure of 10 cm H(2)O. RAGE and vWF:Ag levels and AFC rates were then measured. The rate of AFC was inversely correlated with RAGE levels in the alveolar fluid (p < 0.005). Similarly, the concentration of RAGE in the alveolar fluid was significantly higher in lungs with submaximal AFC, defined in a prespecified analysis as <or= 14%/h, when compared with lungs with preserved AFC (median 0.82 vs 0.43 microg/mL; p < 0.05). In contrast, vWF:Ag levels did not correlate with the rate of AFC. RAGE may be a useful biological marker of alveolar epithelial injury and impaired AFC in donor lungs prior to transplant and perhaps in patients with acute lung injury.
| 19,017,890
|
Ginkgo biloba for prevention of dementia: a randomized controlled trial.
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Ginkgo biloba is widely used for its potential effects on memory and cognition. To date, adequately powered clinical trials testing the effect of G. biloba on dementia incidence are lacking. To determine effectiveness of G. biloba vs placebo in reducing the incidence of all-cause dementia and Alzheimer disease (AD) in elderly individuals with normal cognition and those with mild cognitive impairment (MCI). Randomized, double-blind, placebo-controlled clinical trial conducted in 5 academic medical centers in the United States between 2000 and 2008 with a median follow-up of 6.1 years. Three thousand sixty-nine community volunteers aged 75 years or older with normal cognition (n = 2587) or MCI (n = 482) at study entry were assessed every 6 months for incident dementia. Twice-daily dose of 120-mg extract of G. biloba (n = 1545) or placebo (n = 1524). Incident dementia and AD determined by expert panel consensus. Five hundred twenty-three individuals developed dementia (246 receiving placebo and 277 receiving G. biloba) with 92% of the dementia cases classified as possible or probable AD, or AD with evidence of vascular disease of the brain. Rates of dropout and loss to follow-up were low (6.3%), and the adverse effect profiles were similar for both groups. The overall dementia rate was 3.3 per 100 person-years in participants assigned to G. biloba and 2.9 per 100 person-years in the placebo group. The hazard ratio (HR) for G. biloba compared with placebo for all-cause dementia was 1.12 (95% confidence interval [CI], 0.94-1.33; P = .21) and for AD, 1.16 (95% CI, 0.97-1.39; P = .11). G. biloba also had no effect on the rate of progression to dementia in participants with MCI (HR, 1.13; 95% CI, 0.85-1.50; P = .39). In this study, G. biloba at 120 mg twice a day was not effective in reducing either the overall incidence rate of dementia or AD incidence in elderly individuals with normal cognition or those with MCI. Trial Registration clinicaltrials.gov Identifier: NCT00010803.
| 19,017,911
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Prediction of infarct growth based on apparent diffusion coefficients: penumbral assessment without intravenous contrast material.
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To compare predicted and final infarct lesion volumes determined by processing apparent diffusion coefficient (ADC) maps derived at admission diffusion-weighted (DW) magnetic resonance (MR) imaging in patients with acute stroke and to verify that predicted areas of infarct growth reflect at-risk penumbral regions based on recanalization status. The French legislation waived the requirement for informed patient consent for the described research, which was based on patient medical files. However, patients and/or their relatives were informed that they could decline to participate in the research. Authors tested a semiautomated proprietary image analysis procedure in 98 patients with middle cerebral artery (MCA) stroke by modeling infarct growth on DW imaging-derived ADC maps. Predicted infarct growth (PIG) areas and predicted infarct volumes were correlated with final observed data. In addition, the effect of MCA recanalization on the correlation between predicted and observed infarct growth volumes was qualitatively assessed. Predicted and final infarct volumes (rho = 0.828; 95% confidence interval [CI]: 0.753, 0.882; P < .0001) and infarct growth volumes (rho = 0.506; 95% CI: 0.342, 0.640; P < .0001) were significantly correlated. Visual comparative examination revealed satisfactory qualitative consistency between predicted and follow-up lesion masks. In patients without MCA recanalization, PIG did not differ significantly from final observed infarct growth (median PIG obtained with 0.93 ADC ratio cutoff [PIG(ratio)] of 27.1 cm(3) vs median infarct growth of 19.8 cm(3), P = .17). MCA recanalization revealed an overestimation of PIG (median PIG(ratio) of 24.8 cm(3) vs median infarct growth of 12 cm(3), P = .005), suggesting that the PIG area was part of ischemic penumbra. Data show the feasibility of identifying at-risk ischemic tissue in patients with acute MCA stroke by using semiautomated analysis of ADC maps derived at DW imaging, without intravenous contrast material-enhanced perfusion-weighted imaging.
| 19,017,923
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The phosphoinositide 3-kinase-dependent activation of Btk is required for optimal eicosanoid production and generation of reactive oxygen species in antigen-stimulated mast cells.
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Activated mast cells are a major source of the eicosanoids PGD(2) and leukotriene C(4) (LTC(4)), which contribute to allergic responses. These eicosanoids are produced following the ERK1/2-dependent activation of cytosolic phospholipase A(2), thus liberating arachidonic acid, which is subsequently metabolized by the actions of 5-lipoxygenase and cyclooxygenase to form LTC(4) and PGD(2), respectively. These pathways also generate reactive oxygen species (ROS), which have been proposed to contribute to FcepsilonRI-mediated signaling in mast cells. In this study, we demonstrate that, in addition to ERK1/2-dependent pathways, ERK1/2-independent pathways also regulate FcepsilonRI-mediated eicosanoid and ROS production in mast cells. A role for the Tec kinase Btk in the ERK1/2-independent regulatory pathway was revealed by the significantly attenuated FcepsilonRI-dependent PGD(2), LTC(4), and ROS production in bone marrow-derived mast cells of Btk(-/-) mice. The FcepsilonRI-dependent activation of Btk and eicosanoid and ROS generation in bone marrow-derived mast cells and human mast cells were similarly blocked by the PI3K inhibitors, Wortmannin and LY294002, indicating that Btk-regulated eicosanoid and ROS production occurs downstream of PI3K. In contrast to ERK1/2, the PI3K/Btk pathway does not regulate cytosolic phospholipase A(2) phosphorylation but rather appears to regulate the generation of ROS, LTC(4), and PGD(2) by contributing to the necessary Ca(2+) signal for the production of these molecules. These data demonstrate that strategies to decrease mast cell production of ROS and eicosanoids would have to target both ERK1/2- and PI3K/Btk-dependent pathways.
| 19,017,959
|
T cell-independent spontaneous loss of tolerance by anti-double-stranded DNA B cells in C57BL/6 mice.
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Systemic lupus erythematosus is characterized by loss of tolerance to DNA and other nuclear Ags. To understand the role of T cells in the breaking of tolerance, an anti-DNA site-specific transgenic model of spontaneous lupus, B6x56R, was studied. T cells were eliminated by crossing B6x56R with CD4(-/)(-) or TCRbeta(-/-)delta(-/-) mice, and the effects on anti-dsDNA serum levels, numbers of anti-dsDNA Ab-secreting cells, and isotypes of anti-dsDNA were analyzed. In addition, the development and activation of B cells in these mice were examined. Surprisingly, the presence of T cells made little difference in the development and character of the serum anti-dsDNA Ab in B6x56R mice. At 1 mo of age, anti-dsDNA Abs were somewhat lower in mice deficient in alphabeta and gammadelta T cells. Levels of Abs later were not affected by T cells, nor was autoantibody class switching. B cell activation was somewhat diminished in T cell-deficient mice. Thus, in the B6 background, the presence of an anti-dsDNA transgene led the production of autoantibodies with a specificity and isotype characteristic of murine systemic lupus erythematosus with little influence from T cells. TLR9 also did not appear to play a role. Although we do not yet understand the mechanism of this failure of immunoregulation, these results suggest that similar processes may influence autoimmunity associated with clinical disease.
| 19,017,966
|
TNF receptor-associated factor 5 is required for optimal T cell expansion and survival in response to infection.
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Receptors belonging to the TNF-receptor (TNF-R) superfamily include important costimulatory molecules, many of which specifically affect T cell activation. TNF receptor-associated factors (TRAFs) are recruited to many TNF-R superfamily members and are important modulators of the proximal signaling events that occur at the time of receptor engagement and activation. TRAF5 has been shown to be a positive regulator of a number of these receptors that are involved in T cell costimulation. However, the potential importance of TRAF5 in cellular immune responses to infection or in T cell expansion and memory have not been studied. We report in this study that TRAF5 was required for optimal CD8(+) T cell responses following infection with Listeria monocytogenes expressing OVA (LM-OVA). TRAF5 was necessary for optimal T cell expansion following primary infection with LM-OVA, and its absence resulted in fewer memory CD8(+) T cells following LM-OVA infection, together with higher bacterial loads in the liver. The effect of TRAF5 on CD8(+) T cell expansion was T cell intrinsic and not due to effects of TRAF5 deficiency on APCs. Although their proliferative ability remained intact, CD8(+) T cells from TRAF5(-/-) mice were more sensitive to apoptosis and were unresponsive to the prosurvival effects of the TNF-R superfamily costimulator CD27. Collectively, these studies identify TRAF5 as an important positive signaling element that enhances T cell expansion and pathogen containment by providing a survival advantage to responding Ag-specific CD8(+) T cells during infection.
| 19,017,969
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Persistence of lung CD8 T cell oligoclonal expansions upon smoking cessation in a mouse model of cigarette smoke-induced emphysema.
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The role of adaptive immunity in the development or progression of chronic obstructive pulmonary disease (COPD) remains undefined. Recently, the presence of autoantibodies and autoreactive T cells has been demonstrated in COPD patients. In addition, oligoclonal expansions of lung T cells have been observed in COPD patients, but the overlapping incidence of infections, tumors, and cigarette smoke exposure obscures the antigenic stimulus. We analyzed the TCR Vbeta repertoire of CD4 and CD8 T cells purified from the lungs and spleens of mice chronically exposed to cigarette smoke. In a mouse model of COPD, we demonstrate that chronic cigarette smoke exposure causes oligoclonal expansions of T cells isolated from the lungs, but not spleens. TCR Vbeta repertoire analyses revealed oligoclonal expansions predominantly occurred in lung CD8 T cells, with preferential usage of Vbeta7, Vbeta9, Vbeta13, and Vbeta14. Using nucleotide sequence analysis based on Jbeta analyses, we demonstrate selection of CDR3 amino acid motifs, which strongly suggests Ag-driven oligoclonal T cell expansion. Analysis of the lung TCR Vbeta repertoire of mice with cigarette smoke-induced emphysema, which had undergone smoking cessation for 6 mo, revealed that oligoclonal expansions persisted. This study formally demonstrates that chronic cigarette smoke exposure, alone, causes a persistent adaptive T cell immune response. These findings have important implications for therapeutic approaches in the treatment of COPD, and provide insight into potential mechanisms involved in disease pathogenesis.
| 19,017,996
|
Differentially expressed genes in Mycobacterium tuberculosis H37Rv under mild acidic and hypoxic conditions.
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The survival mechanism of dormant tubercle bacilli is unknown; however, accumulating evidence indicates that Mycobacterium tuberculosis can survive and persist in hypoxic and mildly acidic microenvironments. Such conditions are found in the acidic vacuoles of macrophages, which M. tuberculosis is known to target. We used DECAL (differential expression using customized amplification library) to identify the genes expressed under acidic and hypoxic conditions, following the cultivation of M. tuberculosis H37Rv at an acidic pH and/or under hypoxic or anoxic conditions in vitro. Of 960 clones analysed, 144 genes, consisting of 71 induced and 8 repressed genes, were identified by sequencing and divided into functional categories to characterize their cellular roles. In general, the genes induced under acidic and hypoxic conditions were involved in the biosynthesis of secondary metabolites (e.g. pks4), lipid metabolism, energy production (e.g. pckA) and cell wall biogenesis (e.g. Rv0696 and plcB). The combination of genes identified may explain the energy processing and energy storage of M. tuberculosis during latent infection. These findings not only enhance our understanding of the mechanism of dormancy, but they also may be useful in the design of therapeutic tools and vaccines for latent tuberculosis.
| 19,018,016
|
Persistent Candida parapsilosis funguria associated with an indwelling urinary tract stent for more than 7 years.
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Candiduria is an increasingly common condition, and the lack of effective antifungal treatment in many cases has raised great concern. We report a case of persistent Candida parapsilosis funguria associated with urinary tract instrumentation. Molecular typing suggested that during a 7 year period the C. parapsilosis isolates were all the same strain. Prolonged antifungal therapy and regular catheter replacement failed to eradicate the funguria, but improved urinary symptoms and pyuria. The antifungal susceptibility pattern did not significantly change during the clinical course despite repeated exposure to fluconazole.
| 19,018,034
|
Lasers and optical technologies in facial plastic surgery.
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Lasers and optical technologies play a significant role in aesthetic and reconstructive surgery. The unique ability of optical technologies to target specific structures and layers in tissues to effect chemical, mechanical, or thermal changes makes them a powerful tool in cutaneous rejuvenation, hair removal, fat removal, and treatment of vascular lesions such as port-wine stains, among many other procedures. With the development of adjunct techniques such as epidermal cooling, lasers and optical technologies have become more versatile and safe. The constant improvement of existing applications and the emergence of novel applications such as photodynamic therapy, nanoparticles, spectroscopy, and noninvasive imaging continue to revolutionize aesthetic medicine by offering a minimally invasive alternative to traditional surgery. In the future, therapies will be based on individualized, maximum, safe radiant exposure to deliver optimal dosimetry. Lasers and optical technologies are headed toward safer, easier, more quantifiable, and more individualized therapy.
| 19,018,058
|
New paradigm for macromolecular crystallography experiments at SSRL: automated crystal screening and remote data collection.
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Complete automation of the macromolecular crystallography experiment has been achieved at SSRL through the combination of robust mechanized experimental hardware and a flexible control system with an intuitive user interface. These highly reliable systems have enabled crystallography experiments to be carried out from the researchers' home institutions and other remote locations while retaining complete control over even the most challenging systems. A breakthrough component of the system, the Stanford Auto-Mounter (SAM), has enabled the efficient mounting of cryocooled samples without human intervention. Taking advantage of this automation, researchers have successfully screened more than 200 000 samples to select the crystals with the best diffraction quality for data collection as well as to determine optimal crystallization and cryocooling conditions. These systems, which have been deployed on all SSRL macromolecular crystallography beamlines and several beamlines worldwide, are used by more than 80 research groups in remote locations, establishing a new paradigm for macromolecular crystallography experimentation.
| 19,018,097
|
Mutational and structural studies of the active-site residues in truncated Fibrobacter succinogenes1,3-1,4-beta-D-glucanase.
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1,3-1,4-beta-D-Glucanases (EC 3.2.1.73) specifically hydrolyze beta-1,4-glycosidic bonds located prior to beta-1,3-glycosidic linkages in lichenan or beta-D-glucans. It has been suggested that truncated Fibrobacter succinogenes 1,3-1,4-beta-D-glucanase (TFsbeta-glucanase) can accommodate five glucose rings in its active site upon enzyme-substrate interaction. In this study, 12 mutant enzymes were created by mutating the conserved residues Gln70, Asn72, Gln81 and Glu85 proposed to bind to substrate subsites +1 and +2 and the catalytic properties of these mutants were determined. The most significant change in catalytic activity was observed on mutation of Gln70, with a 299-fold and 498-fold lower k(cat)/K(m) for the mutants Q70A and Q70I, respectively, compared with the wild-type enzyme. Mutagenesis, kinetic and structural studies revealed that the conserved residues surrounding the active site of TFsbeta-glucanase at substrate subsites +1 and +2 play an important role in its catalytic function, with the following order of importance: Gln70 > Asn72 > Glu85 > Gln81. The crystal structure of mutant E85I was determined at 2.2 A resolution. Further analysis of the E85I mutant structure revealed that the loop located at the concave site moved approximately 2 A from its position in the native enzyme complex without changing the core structure.
| 19,018,102
|
Molecular replacement using ab initio polyalanine models generated with ROSETTA.
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The success of the molecular-replacement method for solving protein structures from experimental diffraction data depends on the availability of a suitable search model. Typically, this is derived from a previously solved structure, sometimes by homology modelling. Very recently, Baker, Read and coworkers have demonstrated a successful molecular-replacement case based on an ab initio model generated by ROSETTA [Qian et al. (2007), Nature (London), 450, 259-264]. In this contribution, a number of additional test cases in which ab initio models generated using modest computational resources give correct molecular-replacement solutions are reported. Unsuccessful cases are also reported for comparison and the factors influencing the success of this route to structure solution are discussed.
| 19,018,106
|
Pediatric carcinoma of rectum--Varanasi experience.
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Primary gastrointestinal system malignancies constitute approximately 2% of pediatric neoplasm and of these; colorectal carcinoma is the second most common malignancy. This is one of the rarer diseases in children. We reviewed our records to study the clinical features, outcome and the follow-up of this condition with evaluation of the prognostic factors. Tertiary care Pediatric Surgery centre. Retrospective study. The data of all patients with diagnosis of colorectal carcinoma from January 1986 to January 2006 were reviewed. The confirmation of the diagnosis was by biopsy from the lesion. The age, sex, family history, clinical features, response to the treatment and follow-up were studied. There were four male patients. All had bleeding per rectum as the presenting complaint. Three patients had advanced disease at presentation. All the patients had signet cell adenocarcinoma. The two patients expired and one was lost to follow-up. One patient is alive after one year of follow up and is receiving treatment. Colorectal cancer in children though rare can be a reality, hence any children presenting with pain in abdomen along with doubtful history of constipation and rectal bleeding should be examined carefully with special emphasis on digital rectal examination.
| 19,018,116
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Warfarin-induced skin necrosis in a patient with heparin-induced thrombocytopenia: two diseases or one?
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A 64-year-old woman with colon carcinoma presented with subsegmental pulmonary emboli. Platelet count on presentation was 598 x10(9)/l. The patient was anticoagulated with intravenous heparin. By hospital day 3, heparin was replaced with enoxaparin and warfarin. On hospital day 6, the patient developed a 20 x 15 cm area of necrotic skin on her left hip and a 1 x 3 cm area of necrosis on her right hip. By that time, her platelet count had fallen to 433 x 10(9)/l. Three days later (hospital day 9), anticoagulation was switched from the combination of enoxaparin and warfarin to argatroban. Her platelet count reached a nadir of 82 x 10(9)/l by the 12th hospital day. The areas of skin necrosis had never been sites of heparin injection. Heparin/platelet factor 4 antibody, sent on hospital day 9, returned positive and (14)C-serotonin release assay was also positive. This case illustrates that processes underlying heparin-induced thrombocytopenia (HIT) may also underlie warfarin-induced skin necrosis. Skin necrosis may be the earliest manifestation of HIT and need not be accompanied by thrombocytopenia. This patient's course illustrates that HIT should be considered in all patients presenting with skin necrosis while receiving anticoagulation with heparin or a combination of heparin and warfarin.
| 19,018,128
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The emerging role of magnetic resonance imaging in the diagnosis and management of pulmonary hypertension.
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Pulmonary hypertension is a life-threatening chronic disorder of the pulmonary circulation. Elevated pressure and resistance in the pulmonary vessels lead to progressive right heart failure which results in functional limitations and ultimately the death of most patients. Thus, the monitoring of right ventricular (RV) function is of great importance. Cardiac magnetic resonance imaging (cardiac MRI) has several advantages over other imaging methods. The use of cine acquisition techniques allows precise description of characteristic volumetric and functional variables, such as right ventricular volumes, muscle mass, stroke volume, ejection fraction, or cardiac output. Impaired right ventricular contractility and function have also been assessed using measures like ventricular septal bowing and pressure-volume loops. MRI investigations have been performed to monitor medical treatment, and the improvement in well-established prognostic factors, such as the 6-min walk, were correlated with measures of right ventricular function. Flow-derived parameters of the pulmonary arteries (such as peak velocity, acceleration time and volume, or pulmonary flow profile) are available using velocity-encoded imaging, and may detect early signs of remodelling. Additionally, magnetic resonance angiography is a promising new tool to visualise pulmonary perfusion and to diagnose chronic thromboembolic pulmonary hypertension. The purpose of this review is to summarise recent advances of cardiovascular magnetic resonance imaging, which will play an increasing role in the comprehensive diagnostic work-up of patients with pulmonary hypertension as a tool to monitor the course of the disease and to evaluate new therapeutic approaches.
| 19,018,164
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Advances in prostanoid infusion therapy for pulmonary arterial hypertension.
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Pulmonary arterial hypertension is a rare but progressive and life-threatening disease that presents considerable challenges for both the patient and the caregiver. Though complex, intravenous epoprostenol and treprostinil may improve long-term survival, exercise capacity, hemodynamics, and other clinical symptoms of pulmonary arterial hypertension. Recent advances in infusion pump technology offer ambulatory pump sizes as small as a pager and continuous infusion flow rates as low as 0.1 mL/h, which may provide quality-of-life advantages for patients treated with treprostinil. Transition methods from epoprostenol to treprostinil vary and require close patient monitoring for up to several months. Patients and clinicians must be aware of the differences among delivery systems and the potential for adverse events.
| 19,018,187
|
Anaphylaxis and superior vena cava thrombus in a pediatric patient with acute lymphoblastic leukemia.
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Pediatric patients with malignancies are at significant risk for complications from their underlying condition and medical therapy. Emergency medicine physicians must be quick to suspect life-threatening events, which can present insidiously. We describe a case of anaphylaxis and superior vena cava syndrome in an 18-year-old female patient after polyethylene glycol-conjugated asparaginase chemotherapy for acute lymphoblastic leukemia. Pertinent literature surrounding risk factors, diagnosis, and treatment is also reviewed.
| 19,018,221
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Synaptic ultrastructural alterations anticipate the development of neuroaxonal dystrophy in sympathetic ganglia of aged and diabetic mice.
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Neuroaxonal dystrophy, a distinctive axonopathy characterized by marked enlargement of distal axons, is the hallmark pathologic alteration in aged and diabetic human prevertebral sympathetic ganglia and in corresponding rodent models. Neuroaxonal dystrophy is thought to represent the abnormal outcome of cycles of synaptic degeneration and regeneration; a systematic study of identified axon terminals in aged and diabetic prevertebral ganglia, however, has not previously been performed. We examined the initial changes that develop in presynaptic and postsynaptic elements in sympathetic ganglia of aged and diabetic mice and found numerous synaptic changes involving both presynaptic and postsynaptic elements. Early alterations in presynaptic axon terminal size, vesicle content, and morphology culminate in the development of anastomosing membranous tubulovesicular aggregates, accumulation of autophagosomes, and amorphous debris that form a continuum with progressively larger classically dystrophic swellings. Dendritic changes consist of the development of swellings composed of delicate tubulovesicular elements and mitochondriopathy characterized by increased numbers of small mitochondria and, exclusively in aged ganglia, megamitochondria. These results support the hypothesis that neuroaxonal dystrophy results from progressive changes in presynaptic axon terminals that likely involve membrane dynamics and which are accompanied by distinctive changes in postsynaptic dendritic elements.
| 19,018,240
|
The role of dietary antioxidant insufficiency on the permeability of the blood-brain barrier.
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Our previous studies implicated vitamin E deficiency as a risk factor for equine motor neuron disease, a possible model of human amyotrophic lateral sclerosis, and showed direct effects of this deficiency on brain vascular endothelium. To gain better understanding of the pathogenesis of equine motor neuron disease, we determined the effects of dietary antioxidant insufficiency and the resultant brain tissue oxidative stress on blood-brain barrier permeability. Rats (n = 40) were maintained on a diet deficient of vitamin E for 36 to 43 weeks; 40 controls were fed a normal diet. Permeability of the blood-brain barrier in the cerebral cortex was investigated using rhodamine B, and lipid peroxidation was measured as a marker for oxidative stress. Animals on the vitamin E-deficient diet showed less weight gain and had higher brain lipid peroxidation compared with the controls. Fluorometric studies demonstrated greater rhodamine B in the perivascular compartment and central nervous system parenchyma in rats on the deficient diet compared with controls. These results suggest that a deficiency in vitamin E increases brain tissue oxidative stress and impairs the integrity of the blood-brain barrier. These observations may have relevance to the pathogenesis of amyotrophic lateral sclerosis and other neurologic diseases.
| 19,018,244
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Expression of the zinc-finger transcription factor Snail in adrenocortical carcinoma is associated with decreased survival.
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In this study, we evaluate whether Snail is expressed in adrenocortical cancer (ACC) and if its expression is related to patient outcome. One of the best known functions of the zinc-finger transcription factor Snail is to induce epithelial-to-mesenchymal transition (EMT). Increasing evidence suggests that EMT plays a pivotal role in tumour progression and metastatic spread. Snail and E-cadherin expression were assessed by immunohistochemistry in 26 resected ACCs and real-time quantitative RT-PCR expression analysis was performed. Data were correlated with clinical outcome and in particular with overall patient survival. Seventeen of 26 (65%) ACC tumour samples expressed Snail when assessed by immunohistochemistry. Snail expression was neither detected in normal adrenocortical tissue, nor in benign adrenocortical adenomas. Expression levels were confirmed on the mRNA level by Real-Time-PCR. Survival rates were significantly decreased in Snail-positive tumours compared to Snail-negative tumours: 10 out of 16 vs one out of eight patients succumbed to disease after a median follow up of 14.5 and 28.5 months, respectively (P=0.03). Patients with Snail-expressing ACCs presented in advanced disease (11 out of 12 vs 6 out of 14, P=0.01) and tend to develop distant metastases more frequently than patients with negative staining (7 out of 11 vs two out of eight, P=0.19). In conclusion, we describe for the first time that Snail is expressed in a large subset of ACCs. Furthermore, Snail expression is associated with decreased survival, advanced disease and higher risk of developing distant metastases.
| 19,018,264
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Vagus nerve mediates the protective effects of melanocortins against cerebral and systemic damage after ischemic stroke.
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A vagus nerve-mediated, efferent cholinergic protective pathway activated by melanocortins is operative in circulatory shock and myocardial ischemia. Moreover, melanocortins have neuroprotective effects against brain damage after ischemic stroke. Here we investigated cerebral and systemic pathophysiologic reactions to focal cerebral ischemia in rats induced by intrastriatal microinjection of endothelin-1, and the possible protective role of the melanocortin-activated vagal cholinergic pathway. In the striatum and liver of saline-treated control rats, the activation of extracellular signal-regulated kinases, c-jun N-terminal kinases, and caspase-3, the increase in tumor necrosis factor-alpha (TNF-alpha) concentration and DNA fragmentation, as well as the increase in TNF-alpha plasma levels, occurred 10 and 20 h after the ischemic insult suggesting an activation of inflammatory and apoptotic responses. Treatment with [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH; 3 or 9 h after stroke) suppressed the inflammatory and apoptotic cascades at central and peripheral level. Bilateral vagotomy and pharmacologic blockade of peripheral nicotinic acetylcholine receptors blunted the protective effect of NDP-alpha-MSH. The present results show that focal brain ischemia in rats causes significant effects not only in the brain, but also in the liver. Moreover, our data support the hypothesis that a protective, melanocortin-activated, vagal cholinergic pathway is likely operative in conditions of ischemic stroke.
| 19,018,269
|
Cerebral and Extracranial Neurodegeneration are Strongly Coupled in Parkinson's Disease.
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In idiopathic Parkinson's disease (PD), a generalized Lewy body type-degeneration in the brain as well as extracranial organs was identified. It is unclear, whether cerebral and extracranial Lewy body type-degeneration in PD are coupled or not. To address this question, cerebral [(123)I]FP-CIT SPECT - to quantify cerebral nigrostriatal dopaminergic degeneration - and myocardial [(123)I]MIBG scintigraphy - to quantify extracranial myocardial sympathetic degeneration - were performed in 95 PD patients and 20 healthy controls. At each Hoehn and Yahr stage separately, myocardial MIBG uptake correlated significantly with striatal FP-CIT uptake. No such correlation was found in the controls. Cerebral and extracranial Lewy body type-degeneration in PD do not develop independently from each other but develop in a strongly coupled manner. Obviously cerebral and extracranial changes are driven by at least similar pathomechanisms. Our findings in controls contradict a physiological correlation between nigrostriatal dopaminergic and myocardial sympathetic function.
| 19,018,276
|
The LIM-only protein FHL2 mediates ras-induced transformation through cyclin D1 and p53 pathways.
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Four and a half LIM-only protein 2 (FHL2) has been implicated in multiple signaling pathways that regulate cell growth and tissue homeostasis. We reported previously that FHL2 regulates cyclin D1 expression and that immortalized FHL2-null mouse embryo fibroblasts (MEFs) display reduced levels of cyclin D1 and low proliferative activity. Here we address the contribution of FHL2 in cell transformation by investigating the effects of oncogenic Ras in FHL2-null context. We show that H-RasV12 provokes cell cycle arrest accompanied by accumulation of p53 and p16(INK4a) in immortalized FHL2(-/-) MEFs. These features contrast sharply with Ras transforming activity in wild type cell lines. We further show that establishment of FHL2-null cell lines differs from conventional immortalization scheme by retaining functional p19(ARF)/p53 checkpoint that is required for cell cycle arrest imposed by Ras. However, after serial passages of Ras-expressing FHL2(-/-) cells, dramatic increase in the levels of D-type cyclins and Rb phosphorylation correlates with the onset of cell proliferation and transformation without disrupting the p19(ARF)/p53 pathway. Interestingly, primary FHL2-null cells overexpressing cyclin D1 undergo a classical immortalization process leading to loss of the p19(ARF)/p53 checkpoint and susceptibility to Ras transformation. Our findings uncover a novel aspect of cellular responses to mitogenic stimulation and illustrate a critical role of FHL2 in the signalling network that implicates Ras, cyclin D1 and p53.
| 19,018,287
|
Clostridium perfringens delta toxin is sequence related to beta toxin, NetB, and Staphylococcus pore-forming toxins, but shows functional differences.
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Clostridium perfringens produces numerous toxins, which are responsible for severe diseases in man and animals. Delta toxin is one of the three hemolysins released by a number of C. perfringens type C and possibly type B strains. Delta toxin was characterized to be cytotoxic for cells expressing the ganglioside G(M2) in their membrane. Here we report the genetic characterization of Delta toxin and its pore forming activity in lipid bilayers. Delta toxin consists of 318 amino acids, its 28 N-terminal amino acids corresponding to a signal peptide. The secreted Delta toxin (290 amino acids; 32619 Da) is a basic protein (pI 9.1) which shows a significant homology with C. perfringens Beta toxin (43% identity), with C. perfringens NetB (40% identity) and, to a lesser extent, with Staphylococcus aureus alpha toxin and leukotoxins. Recombinant Delta toxin showed a preference for binding to G(M2), in contrast to Beta toxin, which did not bind to gangliosides. It is hemolytic for sheep red blood cells and cytotoxic for HeLa cells. In artificial diphytanoyl phosphatidylcholine membranes, Delta and Beta toxin formed channels. Conductance of the channels formed by Delta toxin, with a value of about 100 pS to more than 1 nS in 1 M KCl and a membrane potential of 20 mV, was higher than those formed by Beta toxin and their distribution was broader. The results of zero-current membrane potential measurements and single channel experiments suggest that Delta toxin forms slightly anion-selective channels, whereas the Beta toxin channels showed a preference for cations under the same conditions. C. perfringens Delta toxin shows a significant sequence homolgy with C. perfringens Beta and NetB toxins, as well as with S. aureus alpha hemolysin and leukotoxins, but exhibits different channel properties in lipid bilayers. In contrast to Beta toxin, Delta toxin recognizes G(M2) as receptor and forms anion-selective channels.
| 19,018,299
|
Perianal abscess caused by Actinomyces: report of a case.
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Most anal abscesses are caused by anal fistula and invasion of the surrounding tissues by a mixed colonic flora. The treatment comprises excision of the abscess and. if appropriate, fistulectomy. Primary anorectal actinomycosis and perianal actinomycosis are very rare and are caused by Actinomyces, which is a ubiquitous microaerophilic bacterium. Here we report a case of perianal actinomycosis. The patient had a short history of painless perineal induration without fever or leucocytosis with normal routine blood tests. After excision sulphur granules drained from the cavity and the pathological investigations were indicative of perianal actinomycosis. Appropriate surgery and antibiotic treatment healed the perianal infection. After elimination of other diagnoses, e.g. Crohn's disease, tuberculosis and malignant growths, this rare case of perianal actinomycosis should be kept in mind in the differential diagnosis of a painless perianal mass.
| 19,018,464
|
Substitution profile of Delta9-tetrahydrocannabinol, triazolam, hydromorphone, and methylphenidate in humans discriminating Delta9-tetrahydrocannabinol.
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Preclinical evidence suggests that non-cannabinoid neurotransmitter systems are involved in the behavioral and physiological effects of cannabinoids, but relatively little research has been conducted in humans. The aims of this study were to assess whether oral Delta(9)-tetrahydrocannabinol (Delta(9)-THC) would function as a discriminative stimulus in humans and to examine the substitution profile of drugs acting at opioid, GABA, and dopamine systems. Healthy subjects who reported moderate cannabis use were enrolled. Subjects learned to identify when they received oral 25 mg Delta(9)-THC or placebo under double-blind conditions. Once subjects acquired the discrimination (i.e., > or =80% drug-appropriate responding for four consecutive sessions), multiple doses of Delta(9)-THC, the GABA(A) positive modulator triazolam, the micro-opioid agonist hydromorphone and the dopamine reuptake inhibitor methylphenidate were tested to determine if they shared discriminative-stimulus effects with the training dose of Delta(9)-THC. Eight subjects (N = 8) accurately discriminated Delta(9)-THC and completed the study. The training dose of Delta(9)-THC functioned as a discriminative stimulus and produced prototypical subject-rated drug effects. All of the drugs tested produced significant effects on the self-report questionnaires, but only Delta(9)-THC substituted for the training dose. These results suggest that the discriminative-stimulus effects of Delta(9)-THC in humans are not directly mediated through central neurotransmitter systems acted upon by the drugs tested in this study.
| 19,018,520
|
Night/day ratio as predictor of preeclampsia in normoalbuminuric, diabetic women: early signs of blood pressure disorders.
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Day/night ratio from diurnal ambulatory blood pressure (AMBP) in pregnant women with type 1 diabetes mellitus (T1DM) and in non-diabetic women was evaluated for its association with preeclampsia, retinopathy, HbA1c, and birth weight. One hundred and sixty-one women were recruited for AMBP performed with a Spacelab 90207 monitor. The pregnant women were 50 non-diabetic women and 111 T1DM women with normoalbuminuria and no hypertension. ANOVA, regression, and ROC curves analysis were applied. Women with simplex retinopathy had higher night/day ratio and lower birth weight than those without retinopathy. Women who developed preeclampsia had night/day ratio similar to those with simplex retinopathy. In first trimester they had higher blood pressure than those who did not develop preeclampsia. Simplex retinopathy and preeclampsia are associated with a reduced night/day ratio even with normal blood pressure but night/day ratio provides no better prediction of preeclampsia than the absolute values.
| 19,018,544
|
Sonographic findings in adnexal torsion: a report of 34 cases.
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The aim of this study was to correlate the preoperative sonographic findings and operation type in cases with surgically proven adnexal torsion in our clinic. This retrospective study included 34 postmenarchal patients with adnexal torsion who were examined with ultrasound and then operated between November 2003 and October 2007. Surgical procedures performed were divided into two groups: (1) detorsion followed by aspiration or detorsion combined with resection of the adnexal cyst, (2) resection of the whole adnexa. Patients with additional adnexal pathologies as a cause of adnexal torsion were excluded from the study. Twenty-four out of 34 patients (71%) were treated with ovarian conservation and 10 (29%) with resection of the adnexa. Echogenic features of lesions identified in both patient subgroups were similar in appearance. The lowest resection rate was in the group with multicystic appearance (14%), and the highest in solid-cystic group (44.4%). The average mass size was not significantly different between resection (69.3 vs 86.1 mm) and conservation groups. The risk of adnexal resection was higher in cases with an adnexal mass larger than 60 mm (sensitivity 90%, specificity 54.1%) (P = 0.031). The blood flow was present in six of the 21 cases (28.5%). The number of cases who were treated with adnexal resection were significantly more in the group with absent blood flow (P = 0.045). Determination of preoperative sonographic appearance of the mass may be valuable, but it is not specific in the prediction of the operation type of the cases with adnexal torsion. The measurement of the diameter and assessment of blood flow in the adnexal mass might be helpful in detection of the cases who have high risk of adnexal resection.
| 19,018,546
|
Prevalence of urinary incontinence and other urological problems during pregnancy: a questionnaire based study.
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To find out the prevalence of various urological symptoms in pregnant women, the status before pregnancy, and their perceived impact. A questionnaire incorporating various urological problems was prepared and used over 240 pregnant women to know their prevalence in different trimesters of pregnancy and compare them with prevalence before pregnancy. Increased urinary frequency (>10/day) (40.8 vs. 3.8%), nocturia (72.9 vs. 50.6%), burning micturition (21.3 vs. 3.8%), UTI (4.6 vs. 1.6%), urinary hesitancy (14.6 vs. 1.6%), urinary incontinence (25.8 vs. 8.2%) and botheration (22.1 vs. 2.7%) were seen during and before pregnancy, respectively. These also show an increment with advancement of gestation. Urinary incontinence was seen more often with advancing age and parity. There is a very high prevalence of urological symptoms during pregnancy as compared to before pregnancy.
| 19,018,548
|
Fetal macrosomia in African women: a study of 249 cases.
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To determine the incidence and risk factors of macrosomia in a Nigerian centre, and to assess the relation of maternal body mass index (BMI) at birth and of the total weight gain during pregnancy to macrosomia and adverse pregnancy outcome. A retrospective review of fetal macrosomia over a 5-year period. Abia State University Teaching Hospital, Aba in Southeast Nigeria. A total of 9,970 parturients managed from 1 January 1999 to 31 December 2003. Out of 249 documented cases of infants with birth weights > or =4,500 g, 240 (96.4%) maternal and neonatal records of macrosomia were available for review. Maternal and neonatal characteristics of the 240 cases were compared with 8,800 other parturients with singleton fetuses in vertex presentation. Macrosomic babies represented 2.5% of the infants delivered (249 of 9,970). Most of the mothers (92.5%) were multiparous. Maternal median weight gain was 11 kg (7-15), while the mean weight gain was 12.5 kg. Maternal median BMI was 28.1 kg/m(2) at delivery, while the mean BMI was 30.3 kg/m(2) (range 23-40) at delivery. Macrosomia was suspected in 80% on the basis of clinical examination, sonography, and the presence of the following risk factors in association: previous delivery of an infant weighing >4,000 g (62.5%), maternal weight at booking of more than 80 kg (90%), maternal BMI before delivery of > or =28 kg/m(2) (50%), gestational diabetes mellitus (2.5%), and weight increase of more than 13 kg during pregnancy (5%). The mean birth weight of the babies was 4,750 g (4,500-5,000). The overall CS rate was 15%. The difference in the CS rate between these mothers and the control was not significant (P = 0.41). Only 9 (3.8%) mothers were successfully delivered with the aid of ventouse due to delayed second stage of labor. There was a significant difference in the complication rates between the mothers of large infants and the control (P < 0.001). Four maternal deaths were associated with macrosomia for a maternal mortality rate of 1667/100,000. Four infants had shoulder dystocia and associated injuries. The perinatal mortality rate was 112.5/1,000 births. The higher the total body weight at birth, the higher the rate of macrosomia. Macrosomia had implications for high morbidity and mortality in the mothers and their infants. Delivery methods need to be evaluated. Caesarean section should be more readily used.
| 19,018,549
|
Material versus social deprivation and health: a case study of an urban area.
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Socioeconomic factors are one of the main determinants of health inequalities. However, which component of socioeconomic status affects health most and how that relationship should be measured remains an open question. The aim of this study was to compare material and social deprivation indexes in order to determine which better explains health inequalities within an urban area. Following a review of the literature on small area deprivation indexes, a case study of the Italian city Genoa is presented. The city of Genoa is split into 71 small areas [urbanistic units (UU)], each of which has about 9,500 inhabitants. For each small area, socioeconomic indicators were extracted from the 2001 Census, whereas health indicators were computed from the death registry for 2001-2003. Factorial analyses was used to choose the deprivation variables, which were utilised to create two distinct deprivation indexes referring to material and social deprivation, respectively. Both deprivation indexes are positively correlated with health status proxied by standardised mortality ratios (SMRs) under 65. The material index, however, correlates more highly with SMRs than the social index, and thus the material index is the more suitable measure to explain variations in premature mortality within an urban area. Moreover, the two indexes must be kept distinct.
| 19,018,580
|
Analysis of the DDE motif in the Mutator superfamily.
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The eukaryotic Mutator family of transposable elements is widespread in plants. Active or potentially active copies are also found in fungi and protozoans, and sequences related to this family have been detected in metazoans as well. Members of this family are called Mutator-like elements (MULEs). They encode transposases, which contain a region conserved with transposases of the IS256 prokaryotic family, known to harbor a DDE catalytic domain. Different DDE or D34E motifs have been proposed in some groups of eukaryotic MULEs based on primary sequence conservation. On a large number of protein sequences related to, and representative of, all MULE families, we analyzed global conservation, the close environment of different acidic residues and the secondary structure. This allowed us to identify a potential DDE motif that is likely to be homologous to the one in IS256-like transposases. The characteristics of this motif are depicted in each known family of MULEs. Different hypotheses about the evolution of this triad are discussed.
| 19,018,586
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Diversity and distribution of sediment nirS-encoding bacterial assemblages in response to environmental gradients in the eutrophied Jiaozhou Bay, China.
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A gene-clone-library-based molecular approach was used to study the nirS-encoding bacteria-environment relationship in the sediments of the eutrophic Jiaozhou Bay. Diverse nirS sequences were recovered and most of them were related to the marine cluster I group, ubiquitous in estuarine, coastal, and marine environments. Some NirS sequences were unique to the Jiaozhou Bay, such as the marine subcluster VIIg sequences. Most of the Jiaozhou Bay NirS sequences had their closest matches originally detected in estuarine and marine sediments, especially from the Chesapeake Bay, indicating similarity of the denitrifying bacterial communities in similar coastal environments in spite of geographical distance. Multivariate statistical analyses indicated that the spatial distribution of the nirS-encoding bacterial assemblages is highly correlated with environmental factors, such as sediment silt content, NH4+ concentration, and OrgC/OrgN. The nirS-encoding bacterial assemblages in the most hypernutrified stations could be easily distinguished from that of the least eutrophic station. For the first time, the sedimentological condition was found to influence the structure and distribution of the sediment denitrifying bacterial community.
| 19,018,587
|
Simple method to accurately differentiate Candida albicans isolates concurrently using polymorphic patterns of PCR-amplified, species-specific nuclear and mitochondrial targets.
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We describe a simple method to accurately differentiate Candida albicans isolates by concurrent use of the restriction enzyme digestion patterns for PCR products, targeting two species-specific DNA regions originating from genetically different sources, the nuclear and mitochondrial genomes. The target sequence we used as the nuclear gene was derived from the PHO85 gene, a negative regulator of the PHO system, in which we found a restriction size polymorphism within the two alleles of PHO85 in the diploid genome of this fungus. The mitochondrial target was derived from EO3, a species-specific DNA fragment possessing a small size polymorphism among various clinical isolates. Our results should provide a new tool for molecular epidemiological surveys of patients suffering from candidiasis caused by C. albicans.
| 19,018,592
|
The use of sodium hyaluronate-carboxymethylcellulose (HA-CMC) barrier in gynecologic malignancies: a retrospective review of outcomes.
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Concerns exist regarding the safety of sodium hyaluronate-carboxymethylcellulose (HA-CMC, Seprafilm) adhesion barrier in regard to cancer survival as a result of in vitro data demonstrating that hyaluronan, a component of HA-CMC, may promote tumor growth. We sought to determine whether use of HA-CMC is associated with duration of disease-free or overall survival and rates of immediate complication in patients with gynecologic malignancies. We identified 202 consecutive patients with epithelial ovarian, fallopian tube, and primary peritoneal cancer who underwent initial surgical staging or interval debulking at the University of Minnesota between January 2001 and December 2004. Information on patients' demographics, medical history, surgical procedures, postoperative complications, disease stage, histology, adjuvant therapy, and disease-free and overall survival was collected from medical records. Survival curves were compared between patients receiving or not receiving HA-CMC by stratified Cox regression models, log rank, and Wilcoxon tests. The level of significance was set to alpha = .05 for each test. Eighty patients received intraoperative placement of HA-CMC and 122 did not. Immediate postoperative complication rates were equivalent in both groups. Median follow-up was 2.1 years. There was no difference in disease-free survival (5-year estimate 23.6% vs. 33.3%, P = .80) or overall survival (5-year estimate 29.7% vs. 40.3%, P = .75) between those who received HA-CMC and those who did not. Our retrospective analysis suggests that HA-CMC adhesion barrier does not affect disease-free survival or overall survival; nor does it increase the immediate postoperative complication rates in patients undergoing abdominal surgery for ovarian, fallopian tube, and primary peritoneal carcinomas.
| 19,018,596
|
rhBMP-2 modulation of gene expression in infected segmental bone defects.
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The osteoinductive capability of BMPs appears diminished in the setting of acute infection. We applied rhBMP-2 to a segmental defect in a rat femur and measured the expression of key bone formation genes in the presence of acute infection. Types I and II collagen, osteocalcin, and BMP Type II receptor mRNA expression were characterized in 72 Sprague-Dawley rats, which received either bovine collagen carrier with 200 mug rhBMP-2 plus Staphylococcus aureus, carrier with bacteria only, carrier with rhBMP-2 only, or carrier alone. Six animals from each group were euthanized at 1, 2, and 4 weeks. Total RNA was isolated and extracted, and mRNA was determined by real-time comparative quantitative PCR. Infected defects had little expression of collagen I and II and osteocalcin mRNAs, while BMP receptor II expression with infection was greater than carrier-only controls at weeks 2 and 4. Notably, all four genes were upregulated in infected defects in the presence of rhBMP-2. Thus, in a clinical setting with a high risk of infection and nonunion, such as a compound fracture with bone loss, rhBMP-2 may increase the rate and extent of bone formation. Even if infection does occur, rhBMP-2 may allow a quicker overall recovery time.
| 19,018,606
|
Utility of dexrazoxane for the reduction of anthracycline-induced cardiotoxicity.
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Dexrazoxane is a derivative of the powerful metal-chelating agent ethyl enediamine tetra acetic acid. Its cardioprotective effect is thought to be due to its ability to chelate iron and reduce the number of metal ions complexed with anthracycline and, consequently, decrease the formation of superoxide radicals. Preclinical studies have confirmed that dexrazoxane has significant activity as a cardioprotective agent against anthracycline-induced cardiotoxicity. Dexrazoxane is well-tolerated, with myelosuppression being the dose-limiting toxicity in Phase I trials. The cardioprotective utility of dexrazoxane has been further illustrated in a number of randomized trials. In addition no significant difference in survival has been observed between the dexrazoxane and control arms of these trials but, in one, a significantly lower response rate was observed in the dexrazoxane compared to placebo arm. Further trials are required to evaluate the efficacy of dexrazoxane in hematological malignancies as well as the adjuvant treatment of breast cancer. Its use in the paediatric setting and in the management of elderly patients with cardiac comorbidity also requires investigation. Recently, interest has focused on the use of dexrazoxane as an antidote for anthracycline extravasation. In addition the general cytoprotective activity of this drug requires further assessment, as well as selectivity in this context.
| 19,018,683
|
EVEREST study: Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan.
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Acute heart failure syndromes are a common cause of emergency department visits and hospitalization in North America and Europe. Although in-hospital mortality is relatively low, the postdischarge mortality and rehospitalization rates can be as high as 10-15 and 30%, respectively, within 60-90 days following discharge. It appears that the main reason for admission and readmission for heart failure is related to congestion manifested by dyspnea, jugular venous distension and edema. Often, congestion is associated with dilutional hyponatremia that is difficult to treat. Hyponatremia is an important predictor of increased mortality and the available therapies to treat congestion and/or hyponatremia are often ineffective and/or unsafe. Accordingly, there is an unmet need to develop a new agent that effectively relieves congestion due to high filling pressure without worsening renal function and improving or normalizing serum sodium in hyponatremic patients. This paper provides an overview of a new compound, tolvaptan, an oral selective V(2)-vasopressin antagonist in light of the recently published Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial. The biochemical and pharmacological properties are discussed in conjunction with its clinical efficacy and safety, exploring the potential role of tolvaptan in the management of acute heart failure syndromes presenting with or without hyponatremia.
| 19,018,685
|
Analgesic requirements after major abdominal surgery are associated with OPRM1 gene polymorphism genotype and haplotype.
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The association between SNPs of the human OPRM1 gene encoding the micro-opioid receptor and postoperative analgesic requirements in surgical patients remains controversial. Here, we evaluate whether any of the five tag SNPs (A118G, IVS2+G691C, IVS3+G5953A, IVS3+A8449G and TAA+A2109G) representing the four linkage disequilibrium blocks of the OPRM1 gene influences postoperative analgesic requirements. We studied 138 adult Japanese patients who underwent major open abdominal surgery under combined general and epidural anesthesia and received continuous postoperative epidural analgesia with opioids. The 118G homozygous (GG) patients required 24-h postoperative analgesics more than 118A homozygous (AA) and heterozygous (AG) patients. Tag SNP haplotypes also were associated with 24-h postoperative analgesic requirements. These results suggest that OPRM1 gene tag SNP genotypes and haplotypes can primarily contribute to prediction of postoperative analgesic requirements in individual patients undergoing major open abdominal surgery.
| 19,018,716
|
[Nutrition guidelines for advanced chronic kidney disease (ACKD)].
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Prescription of protein intake in CKD is complicated by potential conflicts between goals to delay progression of CKD and preserve nutritional status. Providing a protein intake of about 0.75 g/kg/day appears reasonable in patients with GRF > 30 mL (CKD stages 1-3). In CKD stage 4 and 5, it is recommended to provide a protein intake of about 0.6 g/kg/day to slow progression and minimize accumulation of uremic toxins. - Maintaining adequate energy intake is essential in all stages of CKD. - Assessment of nutritional status in CKD requires multiple markers to assess protein status, fat stores, body composition, and protein and energy intake. - PEM can be considered as an indication for the initiation of kidney replacement therapy. If PEM develops or persists despite attempts to optimize intake, and there is no apparent cause for malnutrition other than intake or anorexia, initiation of dialysis or kidney transplant is indicated in patients with GFR > 15 mL/min. - Nutritional treatment for patients with CKD should include nutritional assessment and education and nutritional planning and follow-up.
| 19,018,743
|
Scythe/BAT3 regulates apoptotic cell death induced by papillomavirus binding factor in human osteosarcoma.
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Papillomavirus binding factor (PBF) was first identified as a transcription factor regulating the promoter activity of human papillomavirus. We previously demonstrated that PBF is an osteosarcoma-associated antigen and 92% of osteosarcoma tissues express PBF in the nucleus. Moreover, PBF-positive osteosarcoma has a significantly poorer prognosis than that with negative expression of PBF. In the present study, we assessed the biological role of PBF in cell survival. Overexpression of PBF induced cell death-mediated lactate dehydrase (LDH) release from 293EBNA cells. Cleaved poly(ADP-ribose) polymerase and active caspase-3 were also detected. However, PBF-induced apoptosis did not affect caspase-9 activity. Next, to identify the apoptosis regulator of PBF, we screened a cDNA library constructed from mRNA of the osteosarcoma cell line OS2000 using a yeast two-hybrid system and isolated Scythe/BAT3. Scythe/BAT3 mRNA was detected in 56% of osteosarcoma tissues and ubiquitously in various normal tissues. Although Scythe/BAT3 was localized to the cytoplasm in normal tissue, it was localized to the nucleus in osteosarcoma tissue. PBF and Scythe/BAT3 also colocalized to the cytoplasm in 293T cells and the nucleus in OS2000. Furthermore, overexpression of Scythe/BAT3 suppressed cell death events that resulted from overexpression of PBF in OS2000, but not in 293EBNA cells. Thus, our results support the ideas that: (i) PBF could induce apoptotic cell death via a caspase-9-independent pathway; (ii) the apoptosis regulator Scythe/BAT3 is a PBF-associated molecule acting as a nucleus-cytoplasm shuttling protein; and (iii) colocalization of PBF and Scythe/BAT3 in the nucleus might be an important factor for survival of osteosarcoma cells.
| 19,018,758
|
Association of visceral fat accumulation and plasma adiponectin with rectal dysplastic aberrant crypt foci in a clinical population.
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The association between obesity and the risk of colorectal cancer (CRC) cannot be easily evaluated because CRC itself is associated with a gradual loss of bodyweight. Aberrant crypt foci (ACF) can be classified as dysplastic ACF or non-dysplastic ACF by magnifying colonoscopy, and dysplastic ACF are thought to be a biomarker of CRC. Ninety-four participants who underwent colonoscopy at Yokohama City University Hospital, Japan, were enrolled in the current study. We detected 557 ACF, including 67 dysplastic ACF (12.0%). Univariate regression analysis was conducted to determine correlations between the number of dysplastic ACF and various potential risk factors, including patient age, waist circumference, body mass index, visceral fat area (VFA), and plasma adiponectin level. The results of multiple regression analysis revealed that the number of dysplastic ACF correlated with age (correlation coefficient r=0.212, P=0.0383) and plasma adiponectin level (r=-0.201, P=0.0371), even after adjustments for sex, waist circumference, body mass index, and VFA. Our univariate correlation analysis data showed a significant correlation with the number of dysplastic ACF with VFA (r=0.238, P=0.0209), no correlation with subcutaneous fat area, and an inverse correlation with the plasma level of adiponectin (r=-0.258, P=0.0118). Thus, our results suggest that aging and visceral fat accumulation could correlate moderately with colorectal carcinogenesis. The novelty of our study lies in the finding that visceral fat accumulation and a low plasma adiponectin level may promote colorectal carcinogenesis; therefore, these obesity-related parameters may serve as novel targets for CRC prevention.
| 19,018,760
|
Primary cutaneous T-cell lymphoma of unspecified type with cytotoxic phenotype: clinicopathological analysis of 27 patients.
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The objective of our study was to investigate the clinicopathological features of the currently ill-defined subtype of primary cutaneous T-cell lymphoma of unspecified type (CTCLU) with a cytotoxic phenotype and no Epstein-Barr virus (EBV) association. A series of 27 patients with CTCLU (median age 49 years; range 25-87 years; 18 men) was reviewed. Performance status scores above 1 (7%), clinical stages above 2 (15%), B symptoms (26%), extracutaneous involvement (30%), and a fatal course within 1 year of diagnosis (19%) were observed infrequently. The International Prognostic Index was high or high to intermediate in 11%, and the Prognostic Index for Peripheral T-cell Lymphoma unspecified was above group 2 in 22%. Notably, the rates of spontaneous regression and T-cell receptor gene rearrangements by polymerase chain reaction analysis were seen in 26 and 17% of our cases, respectively. Histologically, 22 patients had subcutaneous involvement of whom eight showed a lethal clinical course, and five patients without subcutaneous involvement were all survivors. Immunophenotypical and morphological features allowed us to subclassify our cases according to the following four categories: (1) epidermotropic CD8+ T-cell lymphoma (n=5); (2) cutaneous gamma/delta T-cell lymphoma (n=8); (3) cutaneous alpha/beta pleomorphic T-cell lymphoma (n=8); and (4) cutaneous medium/large pleomorphic T-cell lymphoma, not otherwise specified (n=6). All four of these groups of lymphomas exhibited a relatively favorable clinical course compared to previous reports. However, epidermotropic CD8+ T-cell lymphoma appeared to be unique with a higher ratio (80%) of spontaneous regression, a lower ratio (40%) of subcutaneous involvement, and a more favorable clinical course than the other three subcategories.
| 19,018,763
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Phthoxazolin A inhibits prostate cancer growth by modulating tumor-stromal cell interactions.
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Because stroma in tumor tissues can promote prostate cancer development, modulation of tumor-stromal cell interactions may represent an attractive new strategy for cancer treatment. Here, we report that phthoxazolin A and its analog inthomycin B inhibit the growth of human prostate cancer DU-145 cells by modulating tumor-stromal cell interactions. Using an in vitro coculture system, in which prostate cancer cell growth is upregulated by prostate stromal cells (PrSC), we found that phthoxazolin A and inthomycin B strongly inhibited the growth of DU-145 cells when in coculture with PrSC compared to DU-145 cells cultured alone. Although PrSC consist of both fibroblasts and myofibroblasts, phthoxazolin A and inthomycin B inhibited the expression of smooth muscle alpha-actin, a myofibroblast marker, without affecting vimentin and beta-actin expression. Because myofibroblasts secrete various factors that can promote tumor cell growth, we examined whether the inhibitory compounds affected the secretion of such factors from PrSC. Proteomic analysis and reverse transcription-polymerase chain reaction revealed that phthoxazolin A and inthomycin B inhibited the expression of several insulin-like growth factor binding proteins and insulin-like growth factor (IGF)-I by PrSC. Transforming growth factor-beta1 increased myofibroblast numbers and IGF-I levels in PrSC. Phthoxazolin A inhibited transforming growth factor-beta1 activity without altering phosphorylation of the downstream molecule smad2. Furthermore, conditioned medium from phthoxazolin A-treated PrSC failed to increase the phosphorylation of IGF-IR and Akt in DU-145 cells. Taken together, our results suggested that phthoxazolin A acts as a small-molecule modulator of tumor-stromal cell interactions that can indirectly suppress prostate cancer cell growth through inhibition of IGF-I production by PrSC.
| 19,018,764
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Improvement in predicting tumorigenic phenotype of androgen-insensitive human LNCaP prostatic cancer cell subline in recombination with rat urogenital sinus mesenchyme.
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Hormone-refractory prostate cancer, a heterogeneous disease, has varying degrees of androgen sensitivity. To understand the physiological changes in the hormone-refractory state, the present study used a lineage-derived androgen receptor (AR)-positive, androgen-insensitive prostate cancer cell line and evaluated the tumorigenic phenotype, focusing on tumor-stromal interactions in vivo. First, tumorigenic differences of cancer cells alone were examined in an androgen-insensitive AR-positive LNCaP subline, AIDL, compared with those of the androgen-sensitive AR-positive parental LNCaP and the androgen-insensitive AR-negative PC-3 cells transplanted into subcutaneous, sub-renal and prostatic orthotopic graft sites. Next, cancer cells were recombined with rat urogenital sinus mesenchyme (rUGM) to simulate the tumor-stromal microenvironment. Tumors of AIDL and LNCaP without stromal components both formed well-defined globular tumors and contained large blood-filled areas, with no significant difference in tumor growth or histopathology regardless of the cell line's androgen sensitivity or graft site. In contrast, tumors of AIDL and LNCaP recombined with rUGM both showed reduction of blood-filled areas in the tumors and increased tumor growth compared with cancer cells alone. Tumors of AIDL + rUGM recombinants were approximately three times as large as those of LNCaP + rUGM recombinants, whereas tumors of AIDL and LNCaP without rUGM were not different in size. In addition to the tumor size, cell proliferation (Ki-67 labeling index) in tumors of AIDL + rUGM recombinants was significantly higher than that in tumors of LNCaP + rUGM recombinants. Immunoreactivities of AR, E-cadherin and beta-catenin were decreased in AIDL + rUGM recombinants relative to AIDL alone and LNCaP + rUGM recombinants. These results demonstrated that tumorigenic features of androgen-insensitive AR-positive prostate cancer cells could be significantly influenced by rUGM. Therefore, this in vivo recombination model with rUGM may be useful in developing new treatment strategies.
| 19,018,772
|
Novel mutations in DSG1 causing striate palmoplantar keratoderma.
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Striate palmoplantar keratoderma (SPPK) has been shown to be caused by mutations in at least three genes: DSG1, DSP and KRT1. Three families with nine affected members were assessed using a candidate gene-based screening approach. In all three families, new heterozygous mutations were found in DSG1. Direct sequencing of cDNA derived from affected skin in one patient failed to reveal a pathogenic mutation, suggesting that SPPK results from haploinsufficiency for DSG1.
| 19,018,793
|
Intralesional triamcinolone alone or in combination with 5-fluorouracil for the treatment of keloid and hypertrophic scars.
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Keloids and hypertrophic scars are benign growths of dermal collagen that can cause physical and psychological (cosmetic) problems for patients. In this 12-week, double-blind, clinical trial, 40 patients were randomized into two study groups. Patients in group 1 were given intralesional triamcinolone acetonide (TAC), and patients in group 2 were given a combination of TAC and 5-fluorouracil (5-FU); both groups received injections at weekly intervals for 8 weeks. Lesions were assessed for erythema, pruritus, pliability, height, length and width. Four patients in group 1 and three patients in group 2 failed to complete the study. At the 8-week and 12-week follow-up visits, both groups showed an acceptable improvement in nearly all parameters, but these were more significant in the TAC + 5-FU group (P < 0.05 for all except pruritus and percentage of itch reduction). Good to excellent (> 50%) improvement were reported by 20% of the patients in group 1 and 55% of the patients in group 2, which was significantly different (P = 0.02). Good to excellent responses was reported by trained observers as 15% in group 1 and 40% in group 2. Their difference was not significant (P = 0.08). The overall efficacy of TAC + 5-FU was comparable with TAC, but the TAC + 5-FU combination was more acceptable to patients and produced better results.
| 19,018,794
|
Subendocardial viability index is related to the diastolic/systolic time ratio and left ventricular filling pressure, not to aortic pressure: an invasive study in resting humans.
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1. The myocardial perfusion relative to left ventricular (LV) workload may be estimated by the subendocardial viability index (SVI). The SVI is a pressure-time integral ratio: the numerator is the area between aortic and LV pressures during diastolic time (DT) and the denominator is the area under the LV pressure curve during systolic time (ST). New non-invasive tonometric devices allow estimation of SVI but neglect LV end-diastolic pressure (LVEDP) in the calculation. The aim of the present study was to determine the haemodynamic correlates of SVI and to test the effects of neglecting LVEDP on SVI estimation. 2. High-fidelity pressures were recorded at rest at the aortic root and LV level in 38 subjects (33 men/five women; mean (+/-SD) age 47 +/- 14 years; nine controls and 29 patients with various cardiac diseases). The SVI (1.16 +/- 0.28) was positively correlated with the DT/ST ratio (1.71 +/- 0.35; r(2) = 0.81) and was negatively correlated with LVEDP (15 +/- 7 mmHg; multiple r(2) = 0.94). The SVI was not related to aortic pressure (mean, pulse, mean systolic, mean diastolic). In 17 patients with LVEDP > 14 mmHg, the SVI calculated assuming zero LVEDP was 33 +/- 15% higher (range 16-70%) than the actual SVI. 3. The DT/ST ratio was the main determinant of the myocardial perfusion relative to cardiac workload and accounted for 81% of SVI variability, whereas aortic pressure did not contribute. Although LVEDP accounted for only 13% of SVI variability, it should be taken into account in the non-invasive calculation of SVI in patients with known or suspected increases in LV filling pressure.
| 19,018,798
|
Antinociceptive interactions between anandamide and endomorphin-1 at the spinal level.
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1. Although it is well known that the combined administration of synthetic or plant-originated opioids with cannabinoids (CB) results in synergistic antinociception, the effects of combined administration of endogenous ligands acting at micro-opioid and CB receptors are not known. The aim of the present study was to determine the interaction between anandamide (AEA; a CB(1) receptor agonist) and endomorphin-1 (EM-1; a micro-opioid receptor agonist) after intrathecal administration. 2. Nociception was assessed by the paw-withdrawal test after carrageenan-induced inflammation in male Wistar rats. 3. Endomorphin-1 (16.4 pmol to 16.4 nmol) and AEA (4.3-288 nmol) alone dose-dependently decreased carrageenan-induced thermal hyperalgesia, although the highest dose of AEA also exhibited pain-inducing potential. The potency of AEA was approximately 59-fold lower than that of EM-1 (35% effective dose (ED(35)) 194.4 vs 3.3 nmol, respectively). Coadministration of these ligands revealed that combinations of 16.4 pmol EM-1 plus 28.8 or 86.5 nmol AEA were more effective than either drug alone, but other combinations were no more effective than the administration of EM-1 itself. Therefore, coadministration of AEA did not significantly shift the dose-response curve to EM-1. 4. The results of the present study indicate that the coadministration of AEA and EM-1 results in potentiated antihyperalgesia only for a combination of specific doses. Because AEA activates other receptor types (e.g. TRPV1) in addition to CB(1) receptors, the results of the present suggest that, after the coadministration of EM-1 and AEA, complex interactions ensue that may lead to different outcomes compared with those seen following the injection of exogenous ligands.
| 19,018,802
|
Options for upper lip reconstruction: a survey-based analysis.
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Clinical factors such as size and location, but also surgeon experience and comfort level, may influence decisions in reconstructive methods. To survey a select group of surgeons for their reconstructive choices for a moderate-sized upper lip defect. Surveys were mailed to 313 facial plastic surgeons. Survey recipients were asked to rank reconstructive preferences for a specific upper lip defect. Response choices were correlated to predictor variables such as surgeon experience and comfort level. Survey response was 45.6%. Cheek advancement flap was the first choice in 34.4%, followed by Abbé flap (31.2%), myocutaneous rotation flap (20.5%), and nasolabial flap (13.9%), with the nasolabial flap being statistically the least popular (p<.01). For surgeons with more than 20 years' experience and those with less than 10 years' experience, the Abbé flap was the most common first choice (38.9% and 32.4%, respectively). For surgeons with 11 to 20 years experience, the cheek advancement flap was the most common first choice (46.2%). A poll of a select group of surgeons demonstrated variability in their choice of upper lip reconstruction options, although the nasolabial flap was found to be the least-chosen option. Trends in choices based upon experience and comfort level were demonstrated.
| 19,018,829
|
Levetiracetam therapy for treatment of choreoathetosis in dyskinetic cerebral palsy.
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Dyskinetic cerebral palsy (CP) is a movement disorder that is difficult to treat and which causes major disability. We report on two female patients (aged 5y and 8y) who experienced severe perinatal asphyxia and developed dyskinetic CP, clinically characterized by choreoathetosis. Neuropsychological testing of these children showed a low average developmental quotient and no attentional deficit. Monotherapy with levetiracetam was initiated to improve balance control and fine motor skills. Treatment was evaluated by use of video and the Visual Analog Scale. In both children an impressive improvement of balance control and fine motor skills was observed. No side effect occurred. Furthermore, both patients showed more interest and pleasure during activities according to their parents. In a recent multidisciplinary evaluation of the initiated therapy, the parents, the therapist, and the rehabilitation doctor all confirmed that the effect initially observed was still present at 14 and 26 months later. To our knowledge, this report on two patients with dyskinetic CP is the first suggesting that levetiracetam may offer an alternative to the standard therapy of involuntary, uncontrolled movements in this group of patients.
| 19,018,837
|
Magnetic resonance imaging findings in a population-based cohort of children with cerebral palsy.
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The purpose of this study was to investigate the frequency and spectrum of magnetic resonance imaging (MRI) abnormalities in a population of children with cerebral palsy (CP) who were born in the years 2000 and 2001 in Victoria, Australia. In 2000 and 2001, 221 children (126 males, 95 females; mean age 6y [SD 7mo], range 5-7y) with CP, excluding those with CP due to postneonatal causes (6% of all cases), were identified through the Victorian Cerebral Palsy Register. All medical records were systematically reviewed and all available brain imaging was comprehensively evaluated by a single senior MRI radiologist. MRI was available for 154 (70%) individuals and abnormalities were identified in 129 (84%). The study group comprised 88% with a spastic motor type CP; the distribution was hemiplegia in 33.5%, diplegia in 28.5%, and quadriplegia in 37.6% of children. Overall, pathological findings were most likely to be identified in children with spastic hemiplegia (92%) and spastic quadriplegia (84%). Abnormalities were less likely to be identified in non-spastic motor types (72%) and spastic diplegia (52%). The most common abnormalities identified on MRI were periventricular white matter injury (31%), focal ischaemic/haemorrhagic lesions (16%), diffuse encephalopathy (14%), and brain malformations (12%). Dual findings were seen in 3% of patients. This is the first study to document comprehensively the neuroimaging findings of all children identified with CP born over a consecutive 24-month period in a large geographical area.
| 19,018,841
|
Ring(s)-related esophageal meat bolus impaction: biopsy first, dilate later.
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Distal esophageal or Schatzki's rings are a common cause of intermittent solid food dysphagia requiring endoscopic dilation for relief. Similarly, eosinophilic esophagitis (EE) is a rapidly emerging disease in both children and young adults, and manifests as dysphagia to solids and/or episodic food bolus impaction. Endoscopic findings vary considerably among patients with EE, posing significant recognition and management challenges. Esophageal dilation in EE can be painful and risky. This case report describes a patient with acute food bolus impaction due to underlying Schatzki's ring and associated but clinically indolent EE, and highlights some safety aspects of esophageal dilation.
| 19,018,847
|
Esophageal angulation after hiatoplasty and fundoplication: a cause of dysphagia?
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Hiatoplasty is generally considered an essential part of antireflux operations. Posterior closure of an enlarged hiatus may lead to anterior displacement of the esophagus and it may be contributory to postoperative dysphagia. The aims of this study were to (i) measure the normal esophageal anteroposterior angulation, (ii) evaluate the variation of the angulation after laparoscopic hiatoplasty and fundoplication, and (iii) correlate the angulation with postoperative dysphagia. Normal esophageal anteroposterior angle determined by barium preoperative barium esophagram was evaluated based on the study of 100 patients. Postoperative angulation was evaluated based on the study of 32 patients who underwent barium esophagram after laparoscopic hiatoplasty and fundoplication. The results showed that the normal esophageal anteroposterior angle was 150.4 +/- 10.7 (range 119-169) degrees. There was no correlation between the angle and gender (P = 0.6) or age (P = 0.1). Postoperative angle averaged 146.6 +/- 11.7 (range 122-170) degrees. Normal and post-operative angle were not different (P = 0.1). The difference between post- and preoperative angle averaged 0.7 +/- 8.9 (range -15-14). There was no statistically significant difference when pre- and post-operative angles were compared (P = 0.6). De novo dysphagia was present in 31% of the 32 postoperative patients. There was no statistically significant difference when the angles in patients with and without de novo dysphagia were compared (P = 0.2). We concluded that (i) laparoscopic hiatoplasty and fundoplication does not significantly change the esophageal anteroposterior angle; and (ii) de novo dysphagia is not with the esophageal anteroposterior angle.
| 19,018,848
|
Clinicopathological features and prognosis of esophageal cancer in young patients. Is there a difference in outcome?
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The aim of this study was to define the clinicopathological features and prognosis of esophageal cancer in patients 40 years and younger. Between 1990 and 2007, 549 patients with esophageal cancer were enrolled in a retrospective database. Patients were divided into two age groups: Group A was under 40 years old, and group B over 40 years old. The findings for 50 patients (9.1%) aged 40 years or less were compared with those of 499 patients over 40 years old. In the younger group, there were significantly more women (35/15 vs. 231/268, P < 0.001). In the young and old groups, the most frequent histological morphology was squamous cell carcinoma (88% and 75%, respectively), although the percentages were significantly different (P < 0.005). In the younger group, lesions were more frequently located in the middle one-third of the esophagus than in the older group (64% vs. 28.3%, P < 0.001). Group A was more likely to have Stage IIa than older patients. In both groups, the surgical removal of the tumor was the most frequently used choice (70% vs. 56.5%). Survival rates in younger patients at 5 years after resection were 11.4%, similar to those in older patients (16.9%, difference not significant). In the group under age 40, women predominated. Squamous cell carcinoma was the most common histology, followed by adenocarcinoma. Younger patients did not have improved 5-year survival compared with their older counterparts.
| 19,018,851
|
Treatment modality and risk of development of dysplasia and adenocarcinoma in columnar-lined esophagus.
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Columnar metaplasia is the precursor lesion for esophageal adenocarcinoma, resulting from prolonged gastroesophageal reflux. The influence of the efficacy of reflux control on the development of neoplastic change in columnar-lined esophagus is not established. This study compares the rate of development of dysplasia and adenocarcinoma in patients with columnar metaplasia of the esophagus between patients treated pharmacologically and those treated with antireflux surgery. This study is a retrospective review of a cohort of patients enrolled in a multicenter national registry involving 738 patients from seven UK centers. Forty-one were treated with antireflux surgery, 42 with H2 receptor antagonist, 532 with proton pump inhibitor, and 114 with a combination of these medications. Nine had none of these medications or surgery. Total follow-up was 3697 years. Mean age and follow-up for patients treated medically were 61.6 and 4.96 years and surgically were 50.5 and 6.19 years, respectively. No patient in the surgical group developed high-grade dysplasia (HGD) or adenocarcinoma. Twenty patients treated medically developed adenocarcinoma and 10 developed HGD. Hazards ratio comparing pharmacological to surgical therapy for development of all grades of dysplasia and adenocarcinoma 1.77 (P = 0.272). Log rank test comparing antireflux surgery to pharmacological therapy for development of HGD or adenocarcinoma P = 0.1287 and for adenocarcinoma P = 0.2125. Although there was a trend towards greater efficacy of antireflux surgery over pharmacological therapy in reducing the development of dysplasia and adenocarcinoma, this did not reach statistical significance.
| 19,018,855
|
A case of severe aplastic anemia secondary to treatment with lenalidomide for multiple myeloma.
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Lenalidomide is an important contemporary treatment option for patients with multiple myeloma (MM). Rare instances of autoimmune conditions have been observed in association with its use. Although moderate myelosuppression is not uncommonly seen in patients treated with lenalidomide, aplastic anemia has not previously been reported to be associated with this agent. We describe a case of severe aplastic anemia (AA) that was probably induced by lenalidomide. A 64-year-old male patient developed progressive pancytopenia three weeks into therapy with lenalidomide for his relapsed MM. A bone marrow aspirate and biopsy confirmed the diagnosis of AA and suggested the existence of an immunological reaction at the level of marrow. A gradual spontaneous recovery of normal hematopoiesis followed after the lenalidomide discontinuation.
| 19,018,868
|
Towards an evidence-based 'Medicine of the Person': the contribution of psychiatry to health care provision.
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The purpose of this essay is to outline how the conceptual and clinical approaches of psychiatry contribute to increased understanding about the nature of evidence, and the art and science of medicine. It is based on the author's search for a more integrative medicine, the influence of Paul Tournier's 'Medicine de la Personne' and the Institutional Programme on Psychiatry for the Person led by the World Psychiatric Association. Evidence to support this approach from palliative care and general practice is cited, but new educational and research initiatives from other international organizations, such as the World Medical Association, the World Federation for Medical Education and the World Association of Family Practice and the medical Royal Colleges, are proposed.
| 19,018,897
|
Perspectives on evidence-based practice from consumers in the US public mental health system.
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Evidence-based practice (EBP) is a matter of mental health policy in USA. Supporters find it useful in two forms, as generating a list of approved practices and as providing information to practitioners and consumers engaged in shared decision making. Almost nothing has been written about consumer perspectives on EBP. Given that they play an important role in the second form of EBP, this study explores the range and logic of these perspectives and of related views about the role of information in decision making. Four focus groups (n = 38) were held in two settings in a Midwestern state in 2005. Thirty-nine face-to-face semi-structured interviews were conducted at three settings in 2006. Focus group members and interviewees were seriously mentally ill consumers in the public mental health system. Focus group sessions and interviews were audiotaped and transcribed. Thematic categories and subcategories were analysed. Focus group members and interviewees varied among themselves and between groups in their responses, but three major thematic categories emerged in both groups - consumers have positive and negative attitudes towards evidence; consumers seek and receive information from multiple sources; and consumers have competing and complementary principles for decision making. Interviews revealed that although real shared decision making is rare, consumers want to and may be involved in decisions about their care. EBP per se has mostly by-passed consumers in the public mental health system, but at least some want to be better informed about and more involved in their care. Their misgivings about evidence are reasonable and resonate with the principles of the recovery movement.
| 19,018,898
|
Harnessing experience: exploring the gap between evidence-based medicine and clinical practice.
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There is mounting evidence of a gap between Evidence-based Medicine (EBM) and physician clinical practice, in part because EBM is averaged global evidence gathered from exogenous populations which may not be relevant to local circumstances. Local endogenous evidence, collected in particular and 'real world' patient populations may be more relevant, convincing and timely for clinical practice. Evidence Farming (EF) is a concept to provide such local evidence through the systematic collection of clinical experience to guide more effective practice. We report on the findings of a pilot study of 29 individual and three focus group (n = 10) interviews exploring physicians' evaluations how they use multiple sources of information in clinical decision making and their thoughts on EF. Physicians recognize a gap in translating EBM to practice. Physicians reported that when making clinical decisions, they more often rely on clinical experience, the opinions of colleagues and EBM summarizing electronic clinical resources rather than refer directly to EBM literature. Confidence in making decisions based on clinical experience increases over time, yet few physicians reported having systems for tracking their clinical experience in designing treatment plans and patient outcomes. Most physicians saw EF as a promising way to track experience, thereby making scientific evidence more relevant to their own clinical practices. Clinical experience is relatively neglected by the EBM movement, but if that experience were systematically gathered through an approach such as EF, it would meet a need left unfulfilled by EBM.
| 19,018,899
|
The effectiveness of clinical guideline implementation strategies--a synthesis of systematic review findings.
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To establish the effectiveness of clinical guideline implementation strategies. Data sources/study setting Systematic reviews in full text, English language, 1987-2007, reporting any measure of clinical process change or cost-benefit analysis. Overview of secondary evidence Independent critical appraisal using AMSTAR, primary author undertaking all data extraction using a purpose-built form. Principal findings We identified 144 potential papers, from which 33 systematic reviews were included. These reflected 714 primary studies involving 22 512 clinicians, in a range of health care settings. Implementation strategies were varied, rarely comparable, with variable outcomes. Effective implementation strategies included multifaceted interventions, interactive education and clinical reminder systems. Didactic education and passive dissemination strategies were ineffective. Cost-effectiveness studies were rare. Successful guideline implementation strategies should be multifaceted, and actively engage clinicians throughout the process.
| 19,018,923
|
Relationships between statistical measures of agreement: sensitivity, specificity and kappa.
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Cohen's kappa coefficient is presently a standard tool for the analysis of agreement on a binary outcome between two tests. In view of the ubiquity of the use of sensitivity, specificity, raw agreement and kappa in clinical studies, clearly it is advantageous to have a useful analytic relation connecting these measures of agreement. We elaborate on previous work, comment on other results appearing in the literature and discuss analytic formulas relevant to various problems connecting specificity, sensitivity and kappa. For selected values of kappa that range from good to excellent, a graph of the curves representing minimal pairs of sensitivity and specificity is provided. The analytic formulas and graph could be potentially useful to clinicians and biostatisticians in better interpreting the outcomes of an alternative diagnostic test whenever the measures sensitivity, specificity and kappa are employed together.
| 19,018,927
|
Developing a spatial-temporal method for the geographic investigation of shoeprint evidence.
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This article examines the potential of a spatial-temporal method for analysis of forensic shoeprint data. The large volume of shoeprint evidence recovered at crime scenes results in varied success in matching a print to a known shoe type and subsequently linking sets of matched prints to suspected offenders. Unlike DNA and fingerprint data, a major challenge is to reduce the uncertainty in linking sets of matched shoeprints to a suspected serial offender. Shoeprint data for 2004 were imported from the Greater London Metropolitan Area Bigfoot database into a geographic information system, and a spatial-temporal algorithm developed for this project. The results show that by using distance and time constraints interactively, the number of candidate shoeprints that can implicate one or few suspects can be substantially reduced. It concludes that the use of space-time and other ancillary information within a geographic information system can be quite helpful for forensic investigation.
| 19,018,933
|
Revisiting the thermal development of latent fingerprints on porous surfaces: new aspects and refinements.
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Although the ability to develop latent fingerprints on paper using heat alone has been noted previously, it has been considered impractical for casework and inferior to other techniques. Here a new refinement of the technique is demonstrated for the high quality development of latent fingerprints on porous surfaces such as paper. Fingerprints deposited on various papers were developed by exposing them to hot air with a temperature in the vicinity of 300 degrees C, for periods of c. 10-20 sec. Several different heating methods were tested. The novel observation was made that after shorter heating times, fluorescent prints could be observed. These became visible after longer heating times, as noted by earlier workers, but with greatly improved contrast compared with their results. Prints from various donors (and aged prints) were developed with excellent ridge contrast. Direct heating methods (such as with a hot plate or press) produced inferior results. The refined technique, which is simple, safe and inexpensive compared with conventional methods, has great potential for use in forensic laboratories.
| 19,018,940
|
MHC haplotype frequencies in a UK breeding colony of Mauritian cynomolgus macaques mirror those found in a distinct population from the same geographic origin.
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Mauritian cynomolgus macaques have greatly restricted genetic diversity in the MHC region compared to other non-human primates; however, the frequency of common MHC haplotypes among captive-bred populations has not been reported. Microsatellite PCR was used to determine MHC haplotype frequencies among captive macaques at a UK breeding facility. Allele-specific PCR and reference strand conformational analysis were used to determine the allele expression profile of a subset of animals. Haplotypes H3 (21%) and H1 (19%) were most common in the captive population of Mauritian cynomolgus macaques. Predicted alleles were detected by allele-specific PCR-SSP in 98% of animals. Allele expression profiles were similar in animals with identical haplotypes. Mauritian cynomolgus macaques in the UK breeding facility have restricted MHC diversity comparable to a previously described population. Microsatellite-derived haplotypes are highly predictive of allele expression. A selective breeding program has been established to produce MHC-identical animals for biomedical research.
| 19,018,947
|
Visual analysis or semi-automated gray-scale-based color mapping of the carotid plaque: which method correlates the best with the presence of cerebrovascular symptoms and/or lesions on MRI?
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To determine the correlation between carotid plaque morphology, assessed by two different ultrasonographic methods, and presence of cerebrovascular events and/or lesions on magnetic resonance imaging (MRI). Visual analysis of plaque echogenicity using a five-type classification was performed. Further, a semi-automated gray-scale-based color mapping of the whole plaque and of its surface was achieved. There were 31 (35%) symptomatic (23 strokes and 8 transitory ischemic attacks [TIAs]) and 58 (65%) asymptomatic carotid stenoses. MRI lesions related to the carotid stenosis if located in the ipsilateral cortical, subcortical, or watershed area, were present in 27 cases (30%). In a multivariate logistic regression model, degree of stenosis (P= .03) and a predominant red color on the surface (P= .04) were independent factors associated with the presence of cerebrovascular events and/or lesions on MRI. Sensitivity and specificity were, respectively, 80% and 63% by combining degree of stenosis and color mapping of plaque surface. Degree of stenosis and a predominant red color on plaque surface were independent factors associated with the presence of cerebrovascular events and/or lesions on MRI. No correlation was observed with any particular type of plaque based on visual analysis alone.
| 19,018,954
|
Isolation and characterization of alginate-degrading bacteria for disposal of seaweed wastes.
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Isolation of novel alginate degrading bacteria for the disposal of seaweed waste in composting process. Decomposition of alginate polymers was checked by the 3,5-dinitrosalicylic acid (DNS) method for reducing sugar, and absorbance at 235 nm for unsaturated sugar. A bacterium A7 was isolated from wakame compost and confirmed to belong to the genus Gracilibacillus by partial 16S rDNA analysis. The optimum condition for the growth of A7 in a medium containing 5 g l(-1) of sodium alginate is as follows: pH, 8.5-9.5; NaCl, 0.5 mol l(-1); temperature, 30 degrees C and polypeptone as nutrient content, 2-5 g l(-1). In a laboratory-scale composting experiment, the alginate content in wakame compost decreased to 14.3% after 72 h of composting from an initial value of 36%, indicating the effectiveness of alginate decomposition of A7 in wakame composting. The bacterium A7 was found to be alginate lyase-producing in genus Gracilibacillus and effective in degrading alginate to oligosaccharides in wakame during composting process. Development of new methods for the disposal of marine wastes and production of functional products.
| 19,018,967
|
Sterilization effect of atmospheric plasma on Escherichia coli and Bacillus subtilis endospores.
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Escherichia coli and Bacillus subtilis spores were treated with an atmospheric plasma mixture created by the ionization of helium and oxygen to investigate the inactivation efficiency of a low-temperature plasma below 70 degrees C. An electrical discharge plasma was produced at a radio frequency (RF) of 13.56 MHz, connected to a perforated circular electrode with a discharge spacing of 1-15 mm. The discharge gas was helium with 0-2% oxygen. For the plasma treatment, a dried E. coli cell or B. subtilis endospore suspension on a cover-glass was exposed to oxygen downstream of the plasma from holes in an RF-powered electrode. The sterilization effect of the RF plasma was highest with 0.2% oxygen, corresponding to the maximum production of oxygen radicals. Oxygen radicals generated by RF plasma are effective for the destruction of bacterial cells and endospores. Low-temperature atmospheric plasma can be used for the disinfection of diverse objects, especially for the inactivation of bacterial endospores.
| 19,018,968
|
Single nucleotide polymorphism in the ABCG8 transporter gene is associated with gallbladder cancer susceptibility.
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Gallbladder cancer (GBC) usually arises against the background of gallstone disease, which may be causatively related to supersaturation of cholesterol in bile. An imbalance in cholesterol homeostasis because of oversecretion of cholesterol in the gallbladder promotes gallstone formation. The excretion of cholesterol from the liver is regulated by adenosine triphosphate-binding cassette transporter ABCG8. A common genetic polymorphism D19H of ABCG8 associated with gallstone disease may be causatively related to the genetic predisposition of GBC. We aimed to examine the role of ABCG8 D19H (rs11887534) polymorphism in susceptibility to GBC. This study included 171 confirmed GBC patients and 221 controls. Genotyping for the ABCG8 D19H polymorphism was performed by the polymerase chain reaction-restriction fragment length polymorphism method. We observed that in our population the ABCG8 DH genotype frequency was significantly higher in GBC patients [P=0.011; odds ratio (OR)=1.79; 95% confidence interval (CI)=1.1-2.8]. Also, at the allele level, ABCG8H conferred an increased risk for GBC (P=0.023; OR=1.60; 95% CI=1.0-2.4). The risk was more pronounced in GBC patients with gallstones (P=0.027; OR=1.85; 95% CI=1.0-3.1), and in patients with an early onset of the disease (P=0.013; OR=2.55, 95% CI=1.2-5.3). However, there was no modulation of GBC risk because of the ABCG8 polymorphism in a gender-specific manner. The results suggest that the DH genotype and the H allele of the ABCG8 D19H polymorphism are associated with GBC susceptibility. The GBC patients with gallstone disease harbouring the ABCG8 variant allele are at a higher risk, while the effect of this polymorphism on GBC patients without gallstones appears to be small.
| 19,018,975
|
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