tbuckley/cabot-search huggingface dataset:
Meta-analyses on prevalence of selected Parkinson’s nonmotor symptoms before and after diagnosis
Authors: Honglei Chen, Edward J Zhao, Wen Zhang, Yi Lu, Rui Liu, Xuemei Huang, Anna J Ciesielski-Jones, Michele A Justice, Deborah S Cousins, Shyamal Peddada
Journal: Translational Neurodegeneration (2015)

Nonmotor symptoms are common among patients with Parkinson's disease (PD) and some may precede disease diagnosis.We conducted a meta-analysis on the prevalence of selected nonmotor symptoms before and after PD diagnosis, using random-effect models. We searched PubMed (1965 through October/November 2012) for the following symptoms: hyposmia, constipation, rapid eye movement sleep behavior disorder, excessive daytime sleepiness, depression, and anxiety. Eligible studies were publications in English with original data on one or more of these symptoms.The search generated 2,373 non-duplicated publications and 332 met the inclusion criteria, mostly (n = 320) on symptoms after PD diagnosis. For all symptoms, the prevalence was substantially higher in PD cases than in controls, each affecting over a third of the patients. Hyposmia was the most prevalent (75.5% in cases vs. 19.1% in controls), followed by constipation (50% vs. 17.7%), anxiety (39.9% vs. 19.1%), rapid eye movement sleep behavior disorder (37.0% vs. 7.0%), depression (36.6% vs. 14.9%), and excessive daytime sleepiness (33.9% vs. 10.5%). We observed substantial heterogeneities across studies and meta-regression analyses suggested that several factors might have contributed to this. However, the prevalence estimates were fairly robust in several sensitivity analyses. Only 20 studies had data on any symptoms prior to PD diagnosis, but still the analyses revealed higher prevalence in future PD cases than in controls.These symptoms are common among PD patients both before and after diagnosis. Further studies are needed to understand the natural history of nonmotor symptoms in PD and their etiological and clinical implications.
A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis.
Authors: J D McGarry, G P Mannaerts, D W Foster
Journal: Journal of Clinical Investigation (1977)

Studied on the oxidation of oleic and octanoic acids to ketone bodies were carried out in homogenates and in mitochondrial fractions of livers taken from fed and fasted rats. Malonyl-CoA inhibited ketogenesis from the former but not from the latter substrate. The site of inhibition appeared to be the carnitine acyltransferase I reaction. The effect was specific and easily reversible. Inhibitory concentrations were in the range of values obtained in livers from fed rats by others. It is proposed that malonyl-CoA functions as both precursor for fatty acid synthesis and suppressor of fatty acid oxidation. As such, it might be an important element in the carbohydrate-induced sparing of fatty acid oxidation.
Total respiratory impedance and early emphysema
Authors: E Govaerts, M Demedts, KP Van de Woestijne
Journal: European Respiratory Journal (1993)

It can be postulated that patients in early stages of pulmonary emphysema have normal values of total respiratory resistance and reactance. The purpose of this study was to investigate whether pulmonary emphysema, detected functionally by a decrease of the single breath diffusing capacity (DLCO) by at least 25% of predicted, and an increase of the static lung compliance (CLst) by at least 50% of predicted, can be accompanied by normal values of respiratory resistance (Rrs) and reactance (Xrs), measured between 2 and 24 Hz by the forced oscillation technique. In a prospective study, we determined CLst in 26 patients, who had been selected on the basis of normal values of Rrs and Xrs, and a DLCO of less than 75% of predicted. In 17 of these patients, CLst was more than 150% of predicted. Since there were only minor abnormalities on routine lung function tests and chest X-ray, it is likely that these patients presented early emphysema. In the nine other patients, CLst was within normal limits: four suffered from interstitial lung disease; the remaining five were probably in a preliminary stage of early emphysema. In conclusion, early emphysema should systematically be considered as the first diagnosis in patients with normal values of Rrs and Xrs, and a decrease of DLCO. Onset of interstitial lung disease is a possible alternative.
Paraneoplastic pemphigus triggered by Castleman's disease
Authors: H. Wolff, G. Messer
Journal: British Journal of Dermatology (2002)

Journal Article Paraneoplastic pemphigus triggered by Castleman's disease Get access H. Wolff, H. Wolff Department of Dermatology and Allergology, Ludwig‐Maximilians‐Universität, Frauenlobstrasse 9–11, D‐80337 Munich, Germany E‐mail: hans.wolff@lrz.uni‐muenchen.de Search for other works by this author on: Oxford Academic Google Scholar G. Messer G. Messer Department of Dermatology and Allergology, Ludwig‐Maximilians‐Universität, Frauenlobstrasse 9–11, D‐80337 Munich, Germany E‐mail: hans.wolff@lrz.uni‐muenchen.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 2, 1 February 2002, Page 340, https://doi.org/10.1046/j.1365-2133.2002.4653_9.x Published: 01 February 2002
Intracellular Action of Matrix Metalloproteinase-2 Accounts for Acute Myocardial Ischemia and Reperfusion Injury
Authors: Wenjie Wang, Costas J. Schulze, Wilma L. Suarez-Pinzon, Jason R.B. Dyck, Grzegorz Sawicki, Richard Schulz
Journal: Circulation (2002)

Background— Matrix metalloproteinases are best recognized for their ability to degrade the extracellular matrix in both physiological and pathological conditions. However, recent findings indicate that some of them are also involved in mediating acute processes such as platelet aggregation and vascular tone. The acute contractile defect of the heart after ischemia-reperfusion may involve the proteolytic degradation of the thin filament protein troponin I; however, the protease responsible for this remains obscure. Methods and Results— Here we report that matrix metalloproteinase-2 is colocalized with troponin I within the thin myofilaments of cardiomyocytes in ischemic-reperfused hearts and that troponin I is a novel intracellular target for proteolytic cleavage by matrix metalloproteinase-2. Inhibition of matrix metalloproteinase-2 activity prevented ischemia-reperfusion-induced troponin I degradation and improved the recovery of mechanical function of the heart. Conclusions— These data reveal for the first time a novel molecular mechanism by which matrix metalloproteinase-2 causes acute myocardial dysfunction after ischemia-reperfusion-injury and that matrix metalloproteinase-2 has a biological action within the cell.
Fibroproliferation Occurs Early in the Acute Respiratory Distress Syndrome and Impacts on Outcome
Authors: RICHARD P. MARSHALL, GEOFFREY BELLINGAN, SUZANNE WEBB, ANNA PUDDICOMBE, NEIL GOLDSACK, ROBIN J. McANULTY, GEOFFREY J. LAURENT
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The fibroproliferative phase of acute respiratory distress syndrome (ARDS) has traditionally been regarded as a late event but recent studies that suggest increased lung collagen turnover within 24 h of diagnosis challenge this view. We hypothesized that fibroproliferation is initiated early in ARDS, characterized by the presence of fibroblast growth factor activity in the lung and would relate to clinical outcome. Patients fulfilling American/European Consensus Committee criteria for ARDS and control patients ventilated for non-ARDS respiratory failure underwent bronchoalveolar lavage (BAL) and serum sampling within 24 h of diagnosis and again at 7 d. The ability of BAL fluid (BALF) to stimulate human lung fibroblast proliferation in vitro was examined in relation to concentrations of N-terminal peptide for type III procollagen (N-PCP-III) in BALF/serum and clinical indices. At 24 h, ARDS lavage fluid demonstrated potent mitogenic activity with a median value equivalent to 70% (range 31–164) of the response to serum, and was significantly higher than control lavage (32% of serum response, range 11–42; p < 0.05). At 24 h, serum N-PCP-III concentrations were elevated in the ARDS group compared with control patients (2.8 U/ml; range 0.6–14.8 versus 1.1 U/ml; range 0.4–3.7, p < 0.0001) as were BALF N-PCP-III concentrations (2.9 U/ml; range 0.6–11.4 versus 0.46 U/ ml; range 0.00–1.63, p < 0.01). In addition, BALF N-PCP-III concentrations at 24 h were significantly elevated in nonsurvivors of ARDS compared with survivors (p < 0.05). At 7 d, the mitogenic activity remained elevated in the ARDS group compared with control (p < 0.05) and was also significantly higher in ARDS nonsurvivors compared with survivors (67%; range 45–120 versus 31%; range 16–64, p < 0.05). These data are consistent with the hypothesis that fibroproliferation is an early response to lung injury and an important therapeutic target.
New insights into the mechanisms underlying hydrosalpinx fluid formation and its adverse effect on IVF outcome
Authors: L. C. Ajonuma
Journal: Human Reproduction Update (2002)

The adverse effects of hydrosalpinx on the outcome of IVF have been well documented; however, the causes for impaired implantation in patients with hydrosalpinx are poorly understood. Hydrosalpinx fluid has been shown to be toxic to mouse embryos but not human embryos, and this has become a topic of intense debate. An understanding of the mechanisms underlying hydrosalpinx formation following pelvic inflammatory disease appears to be essential in elucidating the causes for reduced implantation in hydrosalpinx patients and providing more rational treatments. This review discusses the mechanisms underlying hydrosalpinx formation and its adverse effect on IVF outcome, with new insights into possible involvement of Fallopian tube epithelial transporters and ion channels, particularly the cystic fibrosis transmembrane conductance regulator (CFTR). Possible links between Chlamydia trachomatis in pelvic inflammatory disease and the subsequent CFTR-mediated events in hydrosalpinx formation leading to infertility in hydrosalpinx are proposed. The causes of reduced implantation, particularly in patients with visible hydrosalpinges shown on ultrasound scanning, are re-examined in light of these possible mechanisms.
Absence of the Lyt-2-,L3T4+ lineage of T cells in mice treated neonatally with anti-I-A correlates with absence of intrathymic I-A-bearing antigen-presenting cell function.
Authors: A M Kruisbeek, J J Mond, B J Fowlkes, J A Carmen, S Bridges, D L Longo
Journal: The Journal of Experimental Medicine (1985)

In an effort to elucidate the role of intrathymic Ia-bearing antigen-presenting cells (APC) on the development of the class II-restricted T cell repertoire, we examined the effect of neonatal anti-I-A treatment on both intrathymic and splenic APC function; on the generation of Lyt-2-,L3T4+, Lyt-2+,L3T4-, and Lyt-2+,L3T4+ T cells; and on the development of class I- and class II-specific T cell functions. Both the thymus and the spleen are completely devoid of Lyt-2-,L3T4+ T cells in young mice treated from birth with anti-I-A, and also lack functions associated with this subset, i.e., alloantigen-specific interleukin 2 production (present report), allo-class II-specific and self-class II-restricted T cell proliferative responses, and helper cell function for the generation of cytotoxic T lymphocyte responses (18). Development of the Lyt-2+,L3T4- subset proceeds undisturbed in these mice, in accord with the previously reported normal levels of cytotoxic T lymphocyte precursors (18). The thymus contains normal numbers of the immature cortical Lyt-2+,L3T4+ cells, indicating that acquisition of the L3T4 marker, in and of itself, is not influenced by anti-I-A treatment. This striking absence of the lineage of T cells responsible for class II-specific T cell functions is correlated with absence of thymic APC function for class II-restricted T cell clones. When anti-I-A-treated mice are allowed to recover from the antibody treatment, splenic and thymic APC function return to normal in 2-3 wk, and thymic Lyt-2-,L3T4+ T cell numbers and functions reappear before such cells are detectable in the spleen. Collectively, these findings suggest that development of the Lyt-2-,L3T4+ lineage of class II-specific T cells is entirely dependent on functional I-A-bearing APC cells in the thymus. In addition, the presence of normal levels of Lyt-2+,L3T4-T cells argues that generation of the two major subsets of T cells (i.e., Lyt-2+,L3T4- and Lyt-2-,L3T4+) occurs through separate events, involving unique sites of interactions between precursor T cells and nonlymphoid major histocompatibility complex-bearing thymus cells.
The impact on risk-factor analysis of different mortality outcomes in COPD patients
Authors: A. Faustini, C. Marino, D. D'Ippoliti, F. Forastiere, V. Belleudi, C. A. Perucci
Journal: European Respiratory Journal (2008)

The aim of the present study was to analyse the role of potential selection processes and their impact when evaluating risk factors for 30-day mortality among patients hospitalised for chronic obstructive pulmonary disease (COPD). A cohort of 26,039 patients aged ≥35 yrs and hospitalised with COPD were enrolled. A 30-day follow-up was carried out using both the cause mortality register (CMR) and the hospital discharge register (HDR). Individual and hospital factors associated with 30-day mortality were studied using both mortality outcomes. The 30-day mortality rate was 1.21·1,000 patient-days −1 (95% confidence interval (CI) 1.14–1.29) using the CMR, and 1.06·1,000 patient-days −1 (95% CI 0.98–1.13) using the HDR. Male patients, the most poorly educated, those who resided outside Rome and those who had more than one hospitalisation in the previous 2 yrs were more likely to die after discharge than when hospitalised. The most frequent cause of in-hospital death was respiratory disease and after discharge, heart disease. Older age, male sex, comorbidities, previous hospitalisations for respiratory failure, and admission to a ward not appropriate to treat respiratory diseases were the most important predictors of 30-day mortality. Using in-hospital 30-day mortality provides a significantly different estimate of the role of specific risk factors.
Related to Testes-Specific, Vespid, and Pathogenesis Protein-1 (RTVP-1) Is Overexpressed in Gliomas and Regulates the Growth, Survival, and Invasion of Glioma Cells
Authors: Tovit Rosenzweig, Amotz Ziv-Av, Cunli Xiang, Wei Lu, Simona Cazacu, Dvir Taler, Cathie G. Miller, Reuven Reich, Yigal Shoshan, Yair Anikster, Gila Kazimirsky, Ronit Sarid, Chaya Brodie
Journal: Cancer Research (2006)

Abstract In this study, we examined the expression and functions of related to testes-specific, vespid, and pathogenesis protein 1 (RTVP-1) in glioma cells. RTVP-1 was expressed in high levels in glioblastomas, whereas its expression in low-grade astrocytomas and normal brains was very low. Transfection of glioma cells with small interfering RNAs targeting RTVP-1 decreased cell proliferation in all the cell lines examined and induced cell apoptosis in some of them. Overexpression of RTVP-1 increased astrocyte and glioma cell proliferation and the anchorage-independent growth of the cells. In addition, overexpression of RTVP-1 rendered glioma cells more resistant to the apoptotic effect of tumor necrosis factor–related apoptosis-inducing ligand and serum deprivation. To delineate the molecular mechanisms involved in the survival effects of RTVP-1, we examined the expression and phosphorylation of various apoptosis-related proteins. We found that overexpression of RTVP-1 decreased the phosphorylation of c-Jun-NH2-kinase and increased the expression of Bcl2 and that the protective effect of RTVP-1 was partially mediated by Bcl2. Finally, we found that RTVP-1 regulated the invasion of glioma cells as was evident by their enhanced migration through Matrigel and by their increased invasion in a spheroid confrontation assay. The increased invasive potential of the RTVP-1 overexpressors was also shown by the increased activity of matrix metalloproteinase 2 in these cells. Our results suggest that the expression of RTVP-1 is correlated with the degree of malignancy of astrocytic tumors and that RTVP-1 is involved in the regulation of the growth, survival, and invasion of glioma cells. Collectively, these findings suggest that RTVP-1 is a potential therapeutic target in gliomas. (Cancer Res 2006; 66(8): 4139-48)
Systemic inflammation in patients with inflammatory joint diseases does not influence statin dose needed to obtain LDL cholesterol goal in cardiovascular prevention
Authors: S Rollefstad, E Ikdahl, J Hisdal, T K Kvien, T R Pedersen, I Holme, A G Semb
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> There is a lipid paradox in rheumatoid arthritis describing that despite low lipids related to systemic inflammation, there is an increased cardiovascular (CV) risk. Our aim was to evaluate if baseline lipid levels or baseline systemic inflammation were associated with the statin dose sufficient to achieve lipid targets in patients with inflammatory joint diseases. <h3>Methods</h3> In this longitudinal, short-term follow-up observational report, we evaluated 197 patients who did and 36 patients who did not reach the recommended low density lipoprotein cholesterol (LDL-c) target. The patients were, after CV risk evaluation, classified to either primary or secondary CV prevention with lipid lowering treatment (LLT). LLT was initiated with statins and adjusted until at least two lipid targets were achieved. Intensive LLT was defined as rosuvastatin ≥20 mg, atorvastatin and simvastatin at the highest dose (80 mg), and conventional LLT were defined as all lower doses. <h3>Results</h3> In an independent sample t test, systemic inflammation or lipid levels at baseline were not associated with the statin dose (intensive or conventional) needed to achieve recommended LDL-c target (C reactive protein/erythrocyte sedimentation rate: p=0.10 and p=0.11, and LDL-c/total cholesterol: p=0.17 and p=0.34, respectively). The baseline inflammatory status and lipid levels in patients who did and did not obtain LDL-c goal were comparable (C reactive protein/erythrocyte sedimentation rate: p=0.32 and p=0.64, and LDL-c/total cholesterol: p=0.20 and p=0.83, respectively). <h3>Conclusions</h3> Systemic inflammation or lipid levels did not influence the intensity of statin treatment needed to obtain guideline recommended lipid targets in CV prevention. Whether the background inflammation in patients with inflammatory joint diseases over time influences the CV risk reduction related to statins is yet unknown.
Prostate Cancer Cells with Stem Cell Characteristics Reconstitute the Original Human Tumor <i>In vivo</i>
Authors: Guangyu Gu, Jialing Yuan, Marcia Wills, Susan Kasper
Journal: Cancer Research (2007)

Abstract Cancer may arise from a cancer stem/progenitor cell that shares characteristics with its normal counterpart. We report the reconstitution of the original human prostate cancer specimen from epithelial cell lines (termed HPET for human prostate epithelial/hTERT) derived from this sample. These tumors can be described in terms of Gleason score, a classification not applied to any of the transgenic mouse models currently developed to mimic human disease. Immunohistochemical and Western blot analyses indicate that they do not express androgen receptor or p63, similar to that reported for prostate stem cells. These cell lines also express embryonic stem markers (Oct4, Nanog, and Sox2) as well as early progenitor cell markers (CD44 and Nestin) in vitro. Clonally derived HPET cells reconstitute the original human tumor in vivo and differentiate into the three prostate epithelial cell lineages, indicating that they arise from a common stem/progenitor cell. Serial transplantation experiments reconstitute the tumors, suggesting that a fraction of parental or clonally derived HPET cells have self-renewal potential. Thus, this model may enhance our understanding of human tumor development and provide a mechanism for studying cancer stem/progenitor cells in differentiation, tumorigenesis, preclinical testing, and the development of drug resistance. [Cancer Res 2007;67(10):4807–15]
Writing legal reports/Giving evidence
Authors: J. Barrett, S. Goldbeck-Wood
Journal: BMJ (1998)

# Writing legal reports {#article-title-2}

Medicolegal work can be a valuable addition to a career portfolio. Psychiatrist James Barrett advises on preparing reports for the legal profession

Most doctors' first opportunities in medicolegal work will arise from their routine practice. Solicitors often seek reports from doctors who happen to be treating their clients. If you write an acceptable report, and offer to write others, then solicitors may put you in a pool of doctors from which they draw when they think that it might benefit their clients' case to seek a medical opinion. If you seek this work, hawking your skills around will not alarm solicitors. Send suitably anonymised samples of reports you have already written, together with an offer to provide more of a similar quality, and details of your rates.

Legal work falls outwith the NHS, and is paid for entirely separately. Patients funded by legal aid will be able to afford about £80 an hour. Refugees - whose cases are funded by the green form scheme - can afford rather less. There is usually a ceiling on how much can be afforded in any one case funded by legal aid or green form - typically set at £400 or so. Some patients will be funding their own cases, and under such circumstances fees are negotiable. Solicitors will usually pay for cases only when they themselves have been paid by the legal aid board, which can mean a delay of many months. While it seems surprising that law firms are not able to make interim payments out of their own reserves, this seems never to be the case.

Before commencing an examination, explain to the patient what the role of any translator is and the purpose of the examination as a whole. Make it clear that the usual rules of medical confidentiality will …
Functional Characterization of Gibberellin-Regulated Genes in Rice Using Microarray System
Authors: Asad Jan, Setsuko Komatsu
Journal: Genomics Proteomics & Bioinformatics (2006)

Abstract Gibberellin (GA) is collectively referred to a group of diterpenoid acids, some of which act as plant hormones and are essential for normal plant growth and development. DNA microarray technology has become the standard tool for the parallel quantification of large numbers of messenger RNA transcripts. The power of this approach has been demonstrated in dissecting plant physiology and development, and in unraveling the underlying cellular signaling pathways. To understand the molecular mechanism by which GA regulates the growth and development of plants, with reference to the monocot model plant—rice, it is essential to identify and analyze more genes and their products at the transcription and translation levels that are regulated by GA. With the availability of draft sequences of two major rice types, indica and japonica rice, it has become possible to analyze global expression profiles of genes on a genome scale. In this review, the progress made in finding new genes in rice leaf sheath using microarray system and their characterization is discussed. It is believed that the findings made in this regard have important implications for understanding the mechanism by which GA regulates the growth and development of rice.