tbuckley/cabot-search huggingface dataset:
Imaging services at the Paralympic Games London 2012: analysis of demand and distribution of workload
Authors: Sarath Bethapudi, Robert S D Campbell, Richard Budgett, Stuart E Willick, Peter Van de Vliet
Journal: British Journal of Sports Medicine (2014)

Very little data have been published on medical imaging services at disability games. 7.9 million euros (£6.6 million, US$11 million) were invested in setting up radiology facilities within purpose built polyclinics at the London 2012 Olympic and Paralympic games. This paper details imaging services at the 2012 Paralympic Games. Data analysis on imaging at 2012 Olympics has been published in a separate paper.To analyse the workload on the polyclinics' radiology services, provided for the Paralympic athletes during the London 2012 Paralympic Games.Data were prospectively collected during the period of the Paralympic games from the Picture Archive Communications System (PACS) and the Radiological Information System (RIS). Data were correlated with the medical encounter database (ATOS).655 imaging episodes were recorded, which comprised 38.8% (n=254) MRI, 33% (n=216) plain radiographs, 24% (n=157) ultrasound scans and 4.2% (n=28) CT scans. Investigations on the Paralympic athletes accounted for 65.2% of workload, with the remainder divided between Paralympic family and workforce.MRI was the most used imaging resource and CT was the least used imaging modality at the Paralympic village polyclinic. Analysis of demographic data provides a useful index for planning radiology infrastructure and manpower at future international competitions for athletes with a disability.
Global ultrasound assessment of structural lesions in osteoarthritis: a reliability study by the OMERACT ultrasonography group on scoring cartilage and osteophytes in finger joints
Authors: H B Hammer, A Iagnocco, A Mathiessen, E Filippucci, F Gandjbakhch, M C Kortekaas, I Möller, E Naredo, R J Wakefield, P Aegerter, M-A D'Agostino
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> Ultrasonography is sensitive for the evaluation of cartilage pathology and degree of osteophytes in patients with hand osteoarthritis (OA). High consistency of assessments is essential, and the OMERACT (Outcome Measures in Rheumatology) ultrasonography group took the initiative to explore the reliability of a global ultrasonography score in patients with hand OA using semiquantitative ultrasonography score of cartilage and osteophytes in finger joints. <h3>Methods</h3> Ten patients with hand OA were examined by 10 experienced sonographers over the course of two days. Semiquantitative scoring (0–3) was performed on osteophytes (carpo-metacarpal 1, metacarpo-phalangeal (MCP) 1–5, proximal interphalangeal 1–5 and distal interphalangeal 2–5 joints bilaterally with an ultrasonography atlas as reference) and cartilage pathology (MCP 2–5 bilaterally). A web-based exercise on static cartilage images was performed a month later. Reliability was assessed by use of weighted κ analyses. <h3>Results</h3> Osteophyte scores were evenly distributed, and the intraobserver and interobserver reliabilities were substantial to excellent (κ range 0.68–0.89 and mean κ 0.65 (day 1) and 0.67 (day 2), respectively). Cartilage scores were unevenly distributed, and the intraobserver and interobserver reliability was fair to moderate (κ range 0.46–0.66 and mean κ 0.39 (day 1) and 0.33 (day 2), respectively). The web-based exercise showed acceptable agreement for cartilage being normal (κ 0.47) or with complete loss (κ 0.68), but poor for the intermediate scores (κ 0.22–0.30). <h3>Conclusions</h3> Use of the present semiquantitative ultrasonography scoring system for cartilage pathology in hand OA is not recommended (while normal or total loss of cartilage may be assessed). However, the OMERACT ultrasonography group will endorse the use of semiquantitative scoring of osteophytes with the ultrasonography atlas as reference.
More Support for the Judicious Use of High-Dose Interleukin-2 in Patients With Advanced Melanoma
Authors: David F. McDermott, Michael B. Atkins
Journal: Journal of Clinical Oncology (2007)

than any other malignancy. 1 Although patients with early-stage disease can be cured with surgical resection, with or without adjuvant therapy, a significant number of patients go on to develop disseminated disease. For patients with metastatic melanoma, common treatment approaches have included chemotherapy and immunotherapy, used alone or in combination. The inability of these agents to improve survival, coupled with their significant toxicity, has justified the enrollment of untreated patients in clinical trials. 2 Dacarbazine (DTIC) and its analog temozolomide are generally considered the most active cytotoxic agents, with response rates of 8% to 20%. Despite a lack of evidence that they improve overallsurvivalwhencomparedwithano-treatmentcontrol,these agents have achieved widespread application as standard therapy. Randomized trials have failed to provide any evidence for the superiority of other single agents, combination chemotherapy, or the addition of tamoxifen or interferon to DTIC compared with DTIC therapy alone. 3 High-dose bolus interleukin-2 (IL-2) was granted US Food and Drug Administration approval based on its abilitytoproducedurablecompleteresponsesinasmallnumberof
Heterogeneity of the molecular lesions in inherited phosphofructokinase deficiency.
Authors: S Vora, M Davidson, C Seaman, A F Miranda, N A Noble, K R Tanaka, E P Frenkel, S Dimauro
Journal: Journal of Clinical Investigation (1983)

Human phosphofructokinase (PFK; EC 2.7.1.11) exists in tetrameric isozymic forms. Muscle and liver contain the homotetramers M4 and L4, whereas erythrocytes contain five isozymes composed of M (muscle) and L (liver) subunits, i.e., M4, M3L, M2L2, ML3, and L4. Inherited defects of erythrocyte PFK are usually partial and are described in association with heterogeneous clinical syndromes. To define the molecular basis and pathogenesis of this enzymopathy, we investigated four unrelated individuals manifesting myopathy and hemolysis (glycogenosis type VII), isolated hemolysis, or no symptoms at all. The three symptomatic patients showed high-normal hemoglobin levels, despite hemolysis and early-onset hyperuricemia. They showed total lack of muscle-type PFK and suffered from exertional myopathy of varying severity. In the erythrocytes, a metabolic crossover was evident at the PFK step: the levels of hexose monophosphates were elevated and those of 2,3-diphosphoglycerate (2,3-DPG) were depressed, causing strikingly increased hemoglobin-oxygen affinity. In all cases, the residual erythrocyte PFK consisted exclusively of L4 isozyme, indicating homozygosity for the deficiency of the catalytically active M subunit. However, presence of immunoreactive M subunit was shown in cultured fibroblasts by indirect immunofluorescence with monoclonal anti-M antibody. The fourth individual was completely asymptomatic, had normal erythrocyte metabolism, and had no evidence of hemolysis. His residual erythrocyte PFK showed a striking decrease of the L4, ML3, and M2L2 isozymes, secondary to a mutant unstable L subunit. Identical alterations of erythrocyte PFK were found in his asymptomatic son, indicating heterozygosity for the mutant unstable L subunit in this kindred. These studies show that, except for the varying severity of the myopathic symptoms, glycogenosis type VII has highly uniform clinical and biochemical features and results from homozygosity for mutant inactive M subunit(s). The absence of anemia despite hemolysis may be explained by the low 2,3-DPG levels. The hyperuricemia may result from hyperactivity of the hexose monophosphate shunt. In contrast, the clinically silent carrier state results from heterozygosity for mutant M or L subunit. Of the two, the M subunit appears to be more critical for adequate glycolytic flux in the erythrocyte, since its absence is correlated with hemolysis.
Risk Factors for Melanoma Among Survivors of Non-Hodgkin Lymphoma
Authors: Clara J.K. Lam, Rochelle E. Curtis, Graça M. Dores, Eric A. Engels, Neil E. Caporaso, Aaron Polliack, Joan L. Warren, Heather A. Young, Paul H. Levine, Angelo F. Elmi, Joseph F. Fraumeni, Margaret A. Tucker, Lindsay M. Morton
Journal: Journal of Clinical Oncology (2015)

Previous studies have reported that survivors of non-Hodgkin lymphoma (NHL) have an increased risk of developing cutaneous melanoma; however, risks associated with specific treatments and immune-related risk factors have not been quantified.We evaluated second melanoma risk among 44,870 1-year survivors of first primary NHL diagnosed at age 66 to 83 years from 1992 to 2009 and included in the Surveillance, Epidemiology, and End Results-Medicare database. Information on NHL treatments, autoimmune diseases, and infections was derived from Medicare claims.A total of 202 second melanoma cases occurred among survivors of NHL, including 91 after chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 111 after other NHL subtypes (cumulative incidence by age 85 years: CLL/SLL, 1.37%; other NHL subtypes, 0.78%). Melanoma risk after CLL/SLL was significantly increased among patients who received infused fludarabine-containing chemotherapy with or without rituximab (n=18: hazard ratio [HR], 1.92; 95% CI, 1.09 to 3.40; n=10: HR, 2.92; 95% CI, 1.42 to 6.01, respectively). Significantly elevated risks also were associated with T-cell activating autoimmune diseases diagnosed before CLL/SLL (n=36: HR, 2.27; 95% CI, 1.34 to 3.84) or after CLL/SLL (n=49: HR, 2.92; 95% CI, 1.66 to 5.12). In contrast, among patients with other NHL subtypes, melanoma risk was not associated with specific treatments or with T-cell/B-cell immune conditions. Generally, infections were not associated with melanoma risk, except for urinary tract infections (CLL/SLL), localized scleroderma, pneumonia, and gastrohepatic infections (other NHLs).Our findings suggest immune perturbation may contribute to the development of melanoma after CLL/SLL. Increased vigilance is warranted among survivors of NHL to maximize opportunities for early detection of melanoma.
Gestational Diabetes Mellitus Increases the Risk of Cardiovascular Disease in Women With a Family History of Type 2 Diabetes
Authors: Darcy B. Carr, Kristina M. Utzschneider, Rebecca L. Hull, Jenny Tong, Tara M. Wallace, Keiichi Kodama, Jane B. Shofer, Susan R. Heckbert, Edward J. Boyko, Wilfred Y. Fujimoto, Steven E. Kahn
Journal: Diabetes Care (2006)

We sought to determine whether a history of gestational diabetes mellitus (GDM) further increases the risk of cardiovascular disease (CVD) in parous women with first-degree relatives with type 2 diabetes.Women with (n = 332) and without (n = 663) a history of GDM were compared regarding 1) the revised National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome criteria, 2) the prevalence of type 2 diabetes, and 3) self-reported CVD.Women with prior GDM were younger (48.6 +/- 0.7 vs. 52.4 +/- 0.6 years [means +/- SE];P < 0.001) and less likely to be postmenopausal (48.3 vs. 57.9%; P < 0.005). Although both groups were obese (BMI 34.4 +/- 1.2 vs. 33.7 +/- 0.6 kg/m(2)), women with prior GDM were more likely to have metabolic syndrome (86.6 vs. 73.5%; P < 0.001) and type 2 diabetes (93.4 vs. 63.3%; P < 0.001). Moreover, they had a higher prevalence of CVD (15.5 vs. 12.4%; adjusted odds ratio 1.85 [95% CI 1.21-2.82];P = 0.005) that occurred at a younger age (45.5 +/- 2.2 vs. 52.5 +/- 1.9 years;P = 0.02) and was independent of metabolic syndrome (1.74 [1.10-2.76]; P = 0.02) and type 2 diabetes (1.56 [1.002-2.43];P < 0.05).Among women with a family history of type 2 diabetes, those with prior GDM were even more likely to not only have CVD risk factors, including metabolic syndrome and type 2 diabetes, but also to have experienced CVD events, which occurred at a younger age. Thus, women with both a family history of type 2 diabetes and personal history of GDM may be especially suitable for early interventions aimed at preventing or reducing their risk of CVD and diabetes.
Diabetes: Have We Got It All Wrong?
Authors: Barbara E. Corkey
Journal: Diabetes Care (2012)

Diabetes is prevalent and chronic (1). A meta-analysis of studies published between 1990 and 2006 showed that in adults, obesity prevalence increased from 13 to 32% between the 1960s and 2004. Currently, 66% of U.S. adults are overweight or obese.

The incidence of diabetes is increasing and afflicting new populations including children and developing societies. Changes in obesity prevalence among children and teens tripled, from nearly 5% to approximately 15% since the 1960s (2). Type 2 diabetes mellitus (T2DM) is a global health problem. In particular, Asia is at the epicenter of the epidemic as these populations develop diabetes at younger ages and at lower BMI levels than people of European origin (3).

Diabetes does not usually diminish over time despite standard treatment. It is a lifelong illness that generally worsens with time and often leads to debilitating complications including cardiovascular disease, neuropathy, retinopathy, and nephropathy (4).

These realities indicate that both our understanding of the disease and our treatment of the disease are inadequate. Current approaches are not working.

It is widely believed that overeating calorie-dense food, particularly a high-fat diet, together with an inactive lifestyle causes obesity. A consequence of obesity is increased circulating lipids and cytokines, indicators of inflammation and inducers of insulin resistance. Obesity and insulin resistance are believed to be the precursors of diabetes in about 20% of subjects. The current standard treatment for diabetes includes diet, exercise, and a biguanide together with agents that increase circulating insulin in an effort to overcome insulin resistance (5).

The term Insulin Resistance Syndrome is used to describe the combination of insulin resistance and compensatory hyperinsulinemia (HI). It is assumed, without evidence, that insulin resistance precedes and causes HI. Insulin resistance purportedly stimulates increased insulin secretion, interpreted as the body’s attempt to overcome the resistance, …
Guarantee of anonymity leads to surge in reports of safety incidents
Authors: Adrian O'Dowd
Journal: BMJ (2006)

Confidence among medical staff in the NHS confidential electronic system for reporting patient safety incidents has soared in recent months with a surge in usage, MPs heard last week.

More doctors are reporting incidents using the confidential system than any other method, Department of Health witnesses told the Public Accounts Committee.

The committee was taking evidence on the National Audit Office report, A Safer Place for Patients: Learning to Improve Patient Safety , which was published last November.

MPs questioned why, according to the report, there had been only 108 responses so far to the anonymous electronic reporting system …
Intrahepatic expression of pre-S1 and pre-S2 antigens in chronic hepatitis B virus infection in relation to hepatitis B virus replication and hepatitis delta virus superinfection.
Authors: C M Chu, Y F Liaw
Journal: Gut (1992)

Hepatocyte expression of pre-S1 and pre-S2 in relation to hepatitis B virus replication (hepatitis B virus-DNA in serum and HBcAg in the liver), histological activity and hepatitis delta virus superinfection was studied by indirect immunofluorescence on frozen sections of liver specimens from 68 patients with chronic hepatitis B virus infection. All 44 patients with chronic type B hepatitis had pre-S1 and pre-S2 display in the liver. The distribution of pre-S1 in the liver was membranous in one, mixed membranous and cytoplasmic in 12, and cytoplasmic in 31. The distribution of pre-S2 was membranous in one, mixed membranous and cytoplasmic in 26, and cytoplasmic in 17. Membranous expression of pre-S1 was significantly more prevalent in patients with active hepatitis B virus replication than in those without (13/28 v 0/16, p &lt; 0.001), regardless of the histological activity, as was membranous expression of pre-S2 (27/28 v 0/16, p &lt; 0.001). In contrast, a significantly higher extent of cytoplasmic expression of pre-S1 and pre-S2 was noted in patients without active hepatitis B virus replication than in those with. Of 24 patients with chronic type D hepatitis virus, eight had active hepatitis B virus replication, and the other 16 did not. The distribution and quantitative expression of pre-S1 and pre-S2 in the liver in these patients also correlated significantly with the status of hepatitis B virus replication and, moreover, showed little or no difference from those without hepatitis delta virus infection. In conclusion, all patients with chronic type B hepatitis had synthesis and display of pre-S1 and pre-S2 in the liver. The distribution and quantitative expression of pre-S1 and pre-S2, however, were closely related to the status of hepatitis B virus replication, but not to the histological activity. Hepatocyte expression of pre-S1 and pre-S2 in chronic type D hepatitis also correlated significantly with status of hepatitis B virus replication, and was not modulated by concurrent hepatitis delta virus infection.
High Expression of a New Marker PCA-1 in Human Prostate Carcinoma
Authors: Noboru Konishi, Mitsutoshi Nakamura, Eiwa Ishida, Keiji Shimada, Eika Mitsui, Rintaro Yoshikawa, Hiroshi Yamamoto, Kazutake Tsujikawa
Journal: Clinical Cancer Research (2005)

Identifying the genetic factors involved in prostate carcinogenesis is critical. Novel cancer-specific markers aid in early detection, in differentiating between cancer and nonmalignant disorders, and in monitoring clinical of prostate disease. We therefore examined differential gene displays in an attempt to identify genes that may be involved in prostate carcinogenesis.Applying fluorescent differential display analysis to human prostate carcinomas, we have identified and cloned several cDNA transcripts. Antisera were raised against synthetic peptides and used in Western blot and immunohistochemical analyses. The mRNAs were also analyzed by real-time reverse transcription-PCR. For functional analysis, we assessed methylmethane sulfonate (MMS)-induced toxicity in COS-7 cells after cDNA transfection.We identified a gene, designated prostate cancer antigen-1 (pca-1), which shows high mRNA expression in prostate carcinoma. Database analysis of the deduced amino acid sequence of PCA-1 indicated high similarity to Escherichia coli AlkB, a DNA alkylation damage repair enzyme. By immunohistochemical analysis, PCA-1 was expressed in a high number of both prostate carcinoma samples and in the atypical cells within high-grade prostatic intraepithelial neoplasias but not in benign prostatic hyperplasia or normal adjacent tissues. PCA-1-transfected COS-7 cells further showed resistance against MMS-induced cell death.These findings suggest that PCA-1 could be a useful diagnostic marker. Furthermore, because this human counterpart of AlkB exhibits a protective function against alkylation damage in mammalian cells, PCA-1 may also serve as a therapeutic target molecule for prostate cancer.
Tau phosphorylation by GSK-3β promotes tangle-like filament morphology
Authors: Carolyn A Rankin, Qian Sun, Truman C Gamblin
Journal: Molecular Neurodegeneration (2007)

Neurofibrillary tangles (NFTs) are intraneuronal aggregates associated with several neurodegenerative diseases including Alzheimer's disease. These abnormal accumulations are primarily comprised of fibrils of the microtubule-associated protein tau. During the progression of NFT formation, disperse and non-interacting tau fibrils become stable aggregates of tightly packed and intertwined filaments. Although the molecular mechanisms responsible for the conversion of disperse tau filaments into tangles of filaments are not known, it is believed that some of the associated changes in tau observed in Alzheimer's disease, such as phosphorylation, truncation, ubiquitination, glycosylation or nitration, may play a role.We have investigated the effects of tau phosphorylation by glycogen synthase kinase-3beta (GSK-3beta) on tau filaments in an in vitro model system. We have found that phosphorylation by GSK-3beta is sufficient to cause tau filaments to coalesce into tangle-like aggregates similar to those isolated from Alzheimer's disease brain.These results suggest that phosphorylation of tau by GSK-3beta promotes formation of tangle-like filament morphology. The in vitro cell-free experiments described here provide a new model system to study mechanisms of NFT development. Although the severity of dementia has been found to correlate with the presence of NFTs, there is some question as to the identity of the neurotoxic agents involved. This model system will be beneficial in identifying intermediates or side reaction products that might be neurotoxic.
Pseudo‐drumsticks in granulocytes of a male with a Yqh+ polymorphism
Authors: Charleen M. Moore, Ronald S. Weinger
Journal: American Journal of Hematology (1980)

Abstract An individual with normal male habitus, body proportions, and secondary sexual characteristics was admitted to the hospital with head trauma. A routine blood smear demonstrated that 36% of the granulocytes had “drumsticks.” Chromosomal analysis revealed a 46, XYqh+ karyotype. The extremely large Y chromosome was located by quinacrine fluorescence in the “drumstick” of the polymorphonuclear granulocytes. The presence of a large Y chromosome may thus produce pseudo‐drumsticks. Fluorescent staining can distinguish between true drumsticks bearing the inactive X of normal females and the pseudo‐drumsticks in a normal male produced by a large Y chromosome.
Gene Therapy for Blindness
Authors: José-Alain Sahel, Botond Roska
Journal: Annual Review of Neuroscience (2013)

Sight-restoring therapy for the visually impaired and blind is a major unmet medical need. Ocular gene therapy is a rational choice for restoring vision or preventing the loss of vision because most blinding diseases originate in cellular components of the eye, a compartment that is optimally suited for the delivery of genes, and many of these diseases have a genetic origin or genetic component. In recent years we have witnessed major advances in the field of ocular gene therapy, and proof-of-concept studies are under way to evaluate the safety and efficacy of human gene therapies. Here we discuss the concepts and recent advances in gene therapy in the retina. Our review discusses traditional approaches such as gene replacement and neuroprotection and also new avenues such as optogenetic therapies. We conjecture that advances in gene therapy in the retina will pave the way for gene therapies in other parts of the brain.