Factors influencing quality of life following lower limb amputation for peripheral arterial occlusive disease: a systematic review of the literature

Background: The majority of lower limb amputations are undertaken in people with peripheral arterial occlusive disease,\ud and approximately 50% have diabetes. Quality of life is an important outcome in lower limb amputations; little is known\ud about what influences it, and therefore how to improve it.\ud Objectives: The aim of this systematic review was to identify the factors that influence quality of life after lower limb\ud amputation for peripheral arterial occlusive disease.\ud Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science and Cochrane databases were searched to identify\ud articles that quantitatively measured quality of life in those with a lower limb amputation for peripheral arterial occlusive\ud disease. Articles were quality assessed by two assessors, evidence tables summarised each article and a narrative\ud synthesis was performed.\ud Study design: Systematic review.\ud Results: Twelve articles were included. Study designs and outcome measures used varied. Quality assessment scores\ud ranged from 36% to 92%. The ability to walk successfully with a prosthesis had the greatest positive impact on quality\ud of life. A trans-femoral amputation was negatively associated with quality of life due to increased difficulty in walking\ud with a prosthesis. Other factors such as older age, being male, longer time since amputation, level of social support and\ud presence of diabetes also negatively affected quality of life.\ud Conclusion: Being able to walk with a prosthesis is of primary importance to improve quality of life for people with lower\ud limb amputation due to peripheral arterial occlusive disease. To further understand and improve the quality of life of this\ud population, there is a need for more prospective longitudinal studies, with a standardised outcome measure

Rehabilitation of hand function after spinal cord injury using a novel handgrip device: a pilot study

BackgroundActivity-based therapy (ABT) for patients with spinal cord injury (SCI), which consists of repetitive use of muscles above and below the spinal lesion, improves locomotion and arm strength. Less data has been published regarding its effects on hand function. We sought to evaluate the effects of a weekly hand-focused therapy program using a novel handgrip device on grip strength and hand function in a SCI cohort.MethodsPatients with SCI were enrolled in a weekly program that involved activities with the MediSens (Los Angeles, CA) handgrip. These included maximum voluntary contraction (MVC) and a tracking task that required each subject to adjust his/her grip strength according to a pattern displayed on a computer screen. For the latter, performance was measured as mean absolute accuracy (MAA). The Spinal Cord Independence Measure (SCIM) was used to measure each subject's independence prior to and after therapy.ResultsSeventeen patients completed the program with average participation duration of 21.3 weeks. The cohort included patients with American Spinal Injury Association (ASIA) Impairment Scale (AIS) A (n = 12), AIS B (n = 1), AIS C (n = 2), and AIS D (n = 2) injuries. The average MVC for the cohort increased from 4.1 N to 21.2 N over 20 weeks, but did not reach statistical significance. The average MAA for the cohort increased from 9.01 to 21.7% at the end of the study (p = .02). The cohort's average SCIM at the end of the study was unchanged compared to baseline.ConclusionsA weekly handgrip-based ABT program is feasible and efficacious at increasing hand task performance in subjects with SCI

Equivalence of Conventionally-Derived and Parthenote-Derived Human Embryonic Stem Cells

As human embryonic stem cell (hESC) lines can be derived via multiple means, it is important to determine particular characteristics of individual lines that may dictate the applications to which they are best suited. The objective of this work was to determine points of equivalence and differences between conventionally-derived hESC and parthenote-derived hESC lines (phESC) in the undifferentiated state and during neural differentiation.hESC and phESC were exposed to the same expansion conditions and subsequent neural and retinal pigmented epithelium (RPE) differentiation protocols. Growth rates and gross morphology were recorded during expansion. RTPCR for developmentally relevant genes and global DNA methylation profiling were used to compare gene expression and epigenetic characteristics. Parthenote lines proliferated more slowly than conventional hESC lines and yielded lower quantities of less mature differentiated cells in a neural progenitor cell (NPC) differentiation protocol. However, the cell lines performed similarly in a RPE differentiation protocol. The DNA methylation analysis showed similar general profiles, but the two cell types differed in methylation of imprinted genes. There were no major differences in gene expression between the lines before differentiation, but when differentiated into NPCs, the two cell types differed in expression of extracellular matrix (ECM) genes.These data show that hESC and phESC are similar in the undifferentiated state, and both cell types are capable of differentiation along neural lineages. The differences between the cell types, in proliferation and extent of differentiation, may be linked, in part, to the observed differences in ECM synthesis and methylation of imprinted genes

A novel myelin P0–specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy

Autoimmune-prone nonobese diabetic mice deficient for B7-2 spontaneously develop an autoimmune peripheral neuropathy mediated by inflammatory CD4+ T cells that is reminiscent of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. To determine the etiology of this disease, CD4+ T cell hybridomas were generated from inflamed tissue–derived CD4+ T cells. A majority of T cell hybridomas were specific for myelin protein 0 (P0), which was the principal target of autoantibody responses targeting nerve proteins. To determine whether P0-specific T cell responses were sufficient to mediate disease, we generated a novel myelin P0–specific T cell receptor transgenic (POT) mouse. POT T cells were not tolerized or deleted during thymic development and proliferated in response to P0 in vitro. Importantly, when bred onto a recombination activating gene knockout background, POT mice developed a fulminant form of peripheral neuropathy that affected all mice by weaning age and led to their premature death by 3–5 wk of age. This abrupt disease was associated with the production of interferon γ by P0-specific T cells and a lack of CD4+ Foxp3+ regulatory T cells. Collectively, our data suggest that myelin P0 is a major autoantigen in autoimmune peripheral neuropathy

Mode equivalence and acceptability of tablet computer-, interactive voice response system-, and paper-based administration of the U.S. National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Background PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. Methods Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0–4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed. Results 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55–0.90); tablet vs paper: 0.81 (0.62–0.96); IVRS vs paper: 0.78 (0.60–0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = −0.04 [−0.16–0.22]; tablet vs paper = −0.02 [−0.11–0.14]; IVRS vs paper = 0.02 [−0.07–0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/−0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported “no problems” responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper. Conclusions Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration. Trial registration NCT Clinicaltrials.gov identifier: NCT0215863

Prevalence of diffuse pancreatic beta islet cell disease with hyperinsulinism: Problems in recognition and management

Among 77 patients with endogenous hyperinsulinism seen in 2 medical centers, diffuse islet cell disease accounted for 17 (22%) patients. Since diffuse islet cell disease poses special problems in management, its prevalence is emphasized in this report. Among these patients with diffuse islet cell disease, there were 11 patients with adenomatosis, 4 with nesidioblastosis, and 2 with islet cell hyperplasia. Six of the 77 patients were found in multiple endocrine neoplasia, type I kindreds; diffuse islet cell disease was documented in 4 of these patients. We outline principles of management in patients with diffuse islet cell disease. Frozen section microscopy failed to identify nesidioblastosis or islet cell hyperplasia. Chez 77 malades, provenant de 2 centres médicaux, qui présentaient un hyperinsulinisme endogène, 17 cas de lésions diffuses des îlots de Langerhans ont été dénombrés. Ce fait est donc loin d'être exceptionnel et cette étude a pour but de le souligner. Parmi ces 17 malades, 11 présentaient des adénomes multiples (adénomatoses), 4 des nésidoblastomes (anomalies tissulaires multifocales), 2 des hyperplasies cellulaires insulaires. Chez ces 77 malades, 6 cas de MEN type I furent individualisés, 4 d'entre eux présentaient une maladie insulaire diffuse. Les auteurs, forts de cette expériences insistent sur les principes du traitement de ce type d'affection. Ils insistent sur le fait que l'étude histologique extemporanée ne permet pas d'identifier les nésidoblastomes et les hyperplasies cellulaires insulaires et que dans 70%–80% des cas les résections pancréatiques ne permettent pas d'obtenir la guérison. Un problema constante para el cirujano que opera pacientes con hiperinsulinismo endógeno es el de qué hacer cuando no se encuentre patología en el curso de la operación una vez realizada la exploración preliminar del páncreas. Los adenomas solitarios de células beta pueden pasar desapercibidos cuando no son palpables; la identificación de la enfermedad difusa de las células insulares plantea muchos problemas. Reconocemos tres alteraciones principales de tipo difuso: adenomatosis de células beta, nesidioblastosis e hiperplasia pancreática de células beta. Además, múltiples macroadenomas pueden coexistir o no con microadenomatosis o con hiperplasia en ciertos pacientes con hiperinsulinismo. Los desórdenes de células insulares de tipo multifocal son particularmente frecuentes en pacientes con Neoplasia Endocrina Multiple Tipo I.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41314/1/268_2005_Article_BF01654942.pd

Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

Experimental autoimmune encephalomyelitis (EAE) is mediated by CD4+ Th1 cells that mainly secrete IFN-γ and TNF-α, important cytokines in the pathophysiology of the disease. Spontaneous remission is, in part, attributed to the down regulation of IFN-γ and TNF-α by TGF-β. In the current paper, we compared weight, histopathology and immunological parameters during the acute and recovery phases of EAE to establish the best biomarker for clinical remission. Female Lewis rats were immunised with myelin basic protein (MBP) emulsified with complete Freund's adjuvant. Animals were evaluated daily for clinical score and weight prior to euthanisation. All immunised animals developed the expected characteristics of EAE during the acute phase, including significant weight loss and high clinical scores. Disease remission was associated with a significant reduction in clinical scores, although immunised rats did not regain their initial weight values. Brain inflammatory infiltrates were higher during the acute phase. During the remission phase, anti-myelin antibody levels increased, whereas TNF-α and IFN-γ production by lymph node cells cultured with MBP or concanavalin A, respectively, decreased. The most significant difference observed between the acute and recovery phases was in the induction of TNF-α levels in MBP-stimulated cultures. Therefore, the in vitro production of this cytokine could be used as a biomarker for EAE remission

Minimising Mortality in Endangered Raptors Due to Power Lines: The Importance of Spatial Aggregation to Optimize the Application of Mitigation Measures

Electrocution by power lines is one of the main causes of non-natural mortality in birds of prey. In an area in central Spain, we surveyed 6304 pylons from 333 power lines to determine electrocution rates, environmental and design factors that may influence electrocution and the efficacy of mitigation measures used to minimise electrocution cases. A total of 952 electrocuted raptors, representing 14 different species, were observed. Electrocuted raptors were concentrated in certain areas and the environmental factors associated with increased electrocution events were: greater numbers of prey animals; greater vegetation cover; and shorter distance to roads. The structural elements associated with electrocutions were shorter strings of insulators, one or more phases over the crossarm, cross-shaped design and pylon function. Of the 952 carcasses found, 148 were eagles, including golden eagle (Aquila chrysaetos), Spanish imperial eagle (Aquila adalberti) and Bonelli's eagle (Aquila fasciata). Electrocuted eagles were clustered in smaller areas than other electrocuted raptors. The factors associated with increased eagle electrocution events were: pylons function, shorter strings of insulators, higher slopes surrounding the pylon, and more numerous potential prey animals. Pylons with increased string of insulators had lower raptor electrocution rates than unimproved pylons, although this technique was unsuccessful for eagles. Pylons with cable insulation showed higher electrocution rates than unimproved pylons, both for raptors and eagles, despite this is the most widely used and recommended mitigation measure in several countries. To optimize the application of mitigation measures, our results recommend the substitution of pin-type insulators to suspended ones and elongating the strings of insulators

Identification of Gene Networks and Pathways Associated with Guillain-Barré Syndrome

BACKGROUND: The underlying change of gene network expression of Guillain-Barré syndrome (GBS) remains elusive. We sought to identify GBS-associated gene networks and signaling pathways by analyzing the transcriptional profile of leukocytes in the patients with GBS. METHODS AND FINDINGS: Quantitative global gene expression microarray analysis of peripheral blood leukocytes was performed on 7 patients with GBS and 7 healthy controls. Gene expression profiles were compared between patients and controls after standardization. The set of genes that significantly correlated with GBS was further analyzed by Ingenuity Pathways Analyses. 256 genes and 18 gene networks were significantly associated with GBS (fold change ≥2, P<0.05). FOS, PTGS2, HMGB2 and MMP9 are the top four of 246 significantly up-regulated genes. The most significant disease and altered biological function genes associated with GBS were those involved in inflammatory response, infectious disease, and respiratory disease. Cell death, cellular development and cellular movement were the top significant molecular and cellular functions involved in GBS. Hematological system development and function, immune cell trafficking and organismal survival were the most significant GBS-associated function in physiological development and system category. Several hub genes, such as MMP9, PTGS2 and CREB1 were identified in the associated gene networks. Canonical pathway analysis showed that GnRH, corticotrophin-releasing hormone and ERK/MAPK signaling were the most significant pathways in the up-regulated gene set in GBS. CONCLUSIONS: This study reveals the gene networks and canonical pathways associated with GBS. These data provide not only networks between the genes for understanding the pathogenic properties of GBS but also map significant pathways for the future development of novel therapeutic strategies