tbuckley/cabot-search huggingface dataset:
Suggested Correlation Between Radiation-Induced Immunosuppression and Radiogenic Leukemia in Mice2
Authors: Neal K. Clapp, John M. Yuhas
Journal: JNCI Journal of the National Cancer Institute (1973)

The reduced incidence of reticulum cell sarcoma in RF mice with glomerulosclerosis (GLO) and the demonstration that GLO partly results from an immune response to wild-type virus-associated antigens have provided a means for the determination of the importance of radiation-induced immunosuppression in leukemogenesis. This finding of reduced leukemia risk in mice with GLO has now been extended to include the 2 radiation-induced types, thymic and myeloid. The incidence of radiation-induced leukemia increased with radiation dose in both GLO-positive and GLO-negative mice, but the presence of GLO was associated within each dose group with a twofold reduction in risk for each leukemia. Doses >100 rads suppressed the immune system and the development of GLO and thereby shifted a fraction of the animals from the low-risk (GLO-positive) group to the high-risk (GLO-negative) group. Since GLO is, at least in part in these RF mice, the product of an immune reaction against a virus-associated antigen, suppressing the ability to cope with leukemogenic virus-associated antigens (suppressing the immune system) contributed to the overall leukemogenic effectiveness of radiation, at least for doses >100 rads. Since suppression of GLO development did not contribute in the lower dose range (≤100 rads) clearly the dose-response curve for radiation-induced leukemia in the RF mouse cannot be linear.
Have the prevalence and incidence of occupational asthma and rhinitis because of laboratory animals declined in the last 25 years?
Authors: I. Folletti, A. Forcina, A. Marabini, A. Bussetti, A. Siracusa
Journal: Allergy (2008)

Data for time trends in the prevalence of occupational asthma (OA) and rhinitis (OR) are not known.To investigate the prevalence and incidence of OA and OR over time.We chose to review studies on the prevalence and incidence of OA and OR due to laboratory animals (LA) as a marker of changing OA and OR patterns over time and analysed 15 cross-sectional and 4 longitudinal studies published from 1980 to 2006.The estimated prevalence of OA, defined as work-related chest symptoms (WRCS), declined from 8.2% in 1976 to 4.2% in 2001 (P < 0.005). When defined by WRCS and positive skin prick test (SPT) to LA, the estimated prevalence of OA was 6.7% in 1977 and 2.9% in 1999 (P < 0.02). The prevalence of OR, defined by WRNS or WRNS and SPT to LA, was not related to study date but was inversely associated with mean exposure duration. In four longitudinal studies no clear trend emerged over time.This review suggests a trend toward a progressive decline in the prevalence of occupational asthma due to laboratory animals, which may be due to the reduction of exposure since the early 1980s. A further reduction of exposure is needed to prevent the onset of occupational rhinitis.
Ethics Consults in Pediatrics and Neonatology Are More Varied and Complex Than Those Reported at St. Jude's Children's Research Hospital
Authors: John J. Paris, Andrew Hawkins
Journal: The American Journal of Bioethics (2015)

"Ethics Consults in Pediatrics and Neonatology Are More Varied and Complex Than Those Reported at St. Jude's Children's Research Hospital." The American Journal of Bioethics, 15(5), pp. 29–30
Abstract P393: Completeness of Medicare Pharmacy Claims for Lipid-Lowering Medications: the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study.
Authors: Lisandro D Colantonio, Shia T Kent, Monika M Safford, Elizabeth Delzell, Meredith L Kilgore, Jeffrey R Curtis, Paul Muntner
Journal: Circulation (2015)

BACKGROUND:  Pharmacy data are increasingly being used to identify medication utilization in epidemiological studies and as a measure of quality of care. The objective of this analysis was to investigate the completeness of Medicare pharmacy claims for lipid-lowering medications (LLM) in a population-based cohort study.   METHODS:  We analyzed data from 891 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants ≥ 65 years of age with Medicare-linked data. Our primary analyses were restricted to participants enrolled in 2006-2007 with Medicare Part D (pharmacy) coverage for 120 days prior to their REGARDS in-home examination at baseline. Secondary analyses were restricted to participants with 182 days of continuous Medicare Part D coverage prior to the in-home examination (n=852). During the baseline examination, bottles for prescription medications taken within the previous 2 weeks were inventoried and drug names were recorded. LLM included statins, ezetimibe, niacin, fibrates and bile acid sequestrants.   RESULTS:  Among the 370 (41.5%) participants with a bottle for a LLM at their REGARDS study examination, 70 (18.9%) participants did not have a Medicare claim for a LLM within the preceding 120 days. Overall agreement between medication inventory and Medicare claims for LLM was 86.8% (95% confidence interval [CI]: 84.4%-88.9%) and agreement above that expected by chance (kappa statistic) was 0.72 (95% CI: 0.68-0.77). Agreement was similar across sub-groups defined by age, self-reported income and education, cognitive status, depressive symptoms, year of enrollment or dual (Medicaid-Medicare) eligible status. The Kappa statistic was lower for black males (0.49; 95% CI: 0.70-0.84) compared with black females (0.74; 95% CI: 0.65-0.82), white males (0.73; 95% CI: 0.65-0.82) and white females (0.77; 95% CI: 0.70-0.84). Among participants with a statin identified in their REGARDS medication inventory, 17.8% did not have a Medicare claim for a statin within 120 days prior to their examination. Overall agreement and the kappa statistic for the comparison between medication inventory and Medicare claims for statins were 87.9% (95% CI: 85.5%-90.0%) and 0.74 (95% CI: 0.69 - 0.79), respectively. Among participants with continuous Medicare Part D coverage for 182 days prior to their REGARDS baseline examination, 14.4% of those with a bottle for LLM had no Medicare claims.   CONCLUSIONS:  A substantial percentage of participants with a LLM identified through the REGARDS medication inventory had no Medicare claims for LLM. Future studies should investigate reasons for the discordance between Medicare claims for LLM and medication inventory, particularly among black males.
DISSEMINATED HERPES ZOSTER
Authors: R R Mittal
Journal: JAMA (1964)

Eleven case of disseminated herpes zoster (DHZ) who were hospitalised in the Dermatovenereology ward from January 1992 to April 1995 were selected for this study. All had classical herpes zoster (HZ) but within another 2 to 15 days had developed aberrant vesicles on the trunk, limbs and face. None of them had serious associated immunosuppressive disorder or malignancy. However, 3 cases had diabetes mellitus, 2 were receiving prednisolone 15 mg daily for the last few days, 2 had anaemia and deficiencies and 1 had a urinary tract infection. Only one patient needed oral acyclovir therapy. All were cured without any sequelae.
Regular review: Management of lateral neck masses in adults
Authors: Michael Gleeson, Amanda Herbert, Aurelia Richards
Journal: BMJ (2000)

One of the most important considerations in an adult presenting with a lump in the neck is that the mass may represent a metastatic deposit from a primary cancer, often but not always in the upper respiratory or alimentary tract (fig 1). This is particularly so for middle aged or elderly patients, especially those who have smoked. In these groups of patients it is important that the primary tumour is found quickly—preferably without open biopsy—so that correct management of the disease can be instituted.1 Often, however, there are avoidable delays in making the diagnosis and obtaining the complete clinical picture. Therefore, an appropriate initial referral must be made for examination of the upper aerodigestive tract, and all those who play a part in the management of neck masses should be aware of the role of fine needle aspiration cytology.

#### Summary points

75% of lateral neck masses in patients over 40 years are caused by malignant tumours

In the absence of overt signs of infection, a lateral neck mass is metastatic squamous cell carcinoma or lymphoma until proved otherwise

The primary tumour can be detected in 50% of patients by clinical examination alone and in a further 10-15% by panendoscopy of the upper aerodigestive tract

Fine needle aspiration biopsy is an accurate, sensitive, inexpensive, and rapid technique that can be performed in the clinic

Excisional and incisional biopsy of cervical metastases results in a 2-3 times increased incidence of local treatment failure when compared with fine needle aspiration cytology

Excisional biopsy of parotid tumours risks damage to the facial nerve and seeding of the wound, and recurrence may develop up to 20 years after the first attempt at resection



Fig 1. 
Location of cervical lymph nodes most frequently affected by metastasis from named primary sites in head and neck



This review is based on …
WHO in 2002: WHO's management: struggling to transform a "fossilised bureaucracy"
Authors: G. Yamey
Journal: BMJ (2002)

Gro Brundtland inherited the leadership of an organisation with major structural problems. WHO was top heavy, male dominated, and rife with cronyism, and staff morale was falling. Has the new management tackled these problems? 

On taking office as director general of the World Health Organization on 21 July 1998, Gro Brundtland was faced with two enormous tasks—to restore the organisation's place on the international stage and to internally reform a failing United Nations agency. There is little doubt that she achieved the former. In this article I consider whether her managerial reforms have been successful.

### Summary points

In the 1990s, WHO was poorly managed, over- centralised, and rife with political appointments

Brundtland established mechanisms to tackle cronyism and raised awareness of the need for greater staff diversity

But WHO is even more centralised now and remains top heavy and dominated by men and representatives of developed countries

Some WHO staff say that senior management stifles open debate and internal dissent

Brundtland has been more successful at raising WHO's profile

internationally than at transforming the organisation internally

Brundtland inherited the leadership of a dysfunctional organisation. In a 1995 editorial, Richard Smith, BMJ editor, argued that WHO was “overcentralised at headquarters and regions, top heavy, poorly managed, and bureaucratic and smells of corruption.”1 Brundtland's reform process, said Jon Liden, her communications adviser, had to “butt against a fossilized UN bureaucratic structure.”

Under Brundtland's predecessor, Hiroshi Nakajima, the number of top ranking posts almost doubled.2 These appointments were widely held to be political, rather than based on merit. When Brundtland took office, for example, there were six assistant director generals. These posts, said Julio Frenk, Mexico's minister of health and a former executive director at WHO, were “geopolitical appointments—each of the permanent members of the UN security council had one.” Cronyism was widespread, …
Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe
Authors: B Abrahamsen, T Masud, A Avenell, F Anderson, H E Meyer, C Cooper, Helen Smith, A Z LaCroix, D Torgerson, A Johansen, R Jackson, L Rejnmark, J Wactawski-Wende, K Brixen, L Mosekilde, J A Robbins, R M Francis
Journal: BMJ (2010)

To identify participants' characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and to assess the influence of dosing regimens and co-administration of calcium.Individual patient data analysis using pooled data from randomised trials.Seven major randomised trials of vitamin D with calcium or vitamin D alone, yielding a total of 68 517 participants (mean age 69.9 years, range 47-107 years, 14.7% men).Studies included were randomised studies with at least one intervention arm in which vitamin D was given, fracture as an outcome, and at least 1000 participants.Logistic regression analysis was used to identify significant interaction terms, followed by Cox's proportional hazards models incorporating age, sex, fracture history, and hormone therapy and bisphosphonate use.Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, P=0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, P=0.07; studies using 10 microg of vitamin D given with calcium: 0.74, 0.60 to 0.91, P=0.005). For vitamin D alone in daily doses of 10 microg or 20 microg, no significant effects were found. No interaction was found between fracture history and treatment response, nor any interaction with age, sex, or hormone replacement therapy.This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 microg is not effective in preventing fractures. By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures.
Determining risk factors for developing systemic lupus erythematosus in patients with discoid lupus erythematosus
Authors: B.F. Chong, J. Song, N.J. Olsen
Journal: British Journal of Dermatology (2011)

Up to 28% of patients with discoid lupus erythematosus (DLE) are susceptible to developing systemic lupus erythematosus (SLE). To better characterize patients with DLE who have a higher potential of developing SLE, we reviewed studies contrasting, firstly, DLE-only patients (i.e. patients with DLE without SLE) and SLE patients with DLE (i.e. patients who are diagnosed with SLE and DLE simultaneously, and patients with SLE who later develop DLE), and secondly, DLE-only patients and patients with DLE who progress to SLE. These studies have commonly identified various clinical and laboratory indicators, such as widespread DLE lesions, arthralgias/arthritis, nail changes, anaemia, leucopenia, high erythrocyte sedimentation rates (ESRs) and high titres of antinuclear antibodies (ANAs), which are associated with progression to SLE in patients with DLE, and SLE patients with DLE. Limitations of these studies include inadequate follow-up time, small numbers of patients with DLE converting to SLE, outdated criteria for SLE diagnosis and retrospective study designs. However, because of the risk of SLE development in patients with DLE, complete skin examinations, joint assessments and laboratory tests including ANA, ESR and full blood counts should be performed regularly for patients with DLE. A prospective study following patients with DLE who do or do not develop SLE is currently underway through the Cutaneous Lupus Registry at the University of Texas Southwestern Medical Center. It will seek to identify clinical features and biomarkers that improve our assessment of risk of systemic spread in these patients.
Abstract 19810: A Significant Decrease in Early Confirmed Left Ventricular Assist Device Pump Thrombosis: Recent Observations from a Large Multi-Institutional Experience
Authors: John M Stulak, John A Schirger, Lyle D Joyce, Keith D Aaronson, Francis D Pagani, Mary E Davis, Nicholas A Haglund, Simon Maltais
Journal: Circulation (2014)

Introduction: Recent reports have documented an abrupt increase in 3-month confirmed HeartMate II left ventricular assist device (LVAD) thrombosis beginning in 2011 without a plateau observed to date. Because very little data exist from multi-institutional efforts, we report our experience. Methods: From January 2004 to December 2013, 516 pt underwent HeartMate II LVAD implant at three institutions (University of Michigan (n=254), Mayo Clinic Rochester (n=205), and Vanderbilt Heart and Vascular Institute (n=57)). Median age at implant was 60 yr (range, 18-82) and 428 (83%) were male. Confirmed pump thrombosis at 3 months was defined as thrombus found in the blood-contacting surfaces of the pump at the time of urgent transplant, device exchange or autopsy. Pt without at least 3 months of follow-up were excluded. Results: Confirmed pump thrombosis occurred in 9 pt within 3 months post implant. The incidence was greatest in the year 2012 (5.3%). Following this peak, the incidence of 3-month confirmed pump thrombosis decreased significantly to 2.9% (Figure). Significant differences in preoperative characteristics between patients with pump thrombosis and without thrombosis included female sex (36% vs. 16%, p=0.01), bridge to transplant (77% vs. 54%, p=0.03), atrial fibrillation (55% vs. 32%, p=0.04), and preop platelet count (231,000 vs. 172,000, p&lt;0.001). Follow-up was available in all for a total of 857 patient years of support. At a median follow-up of 1.2 years (max., 9.8 years), a similar proportion of patients were alive (73% vs. 74%, p=0.9). Conclusions: We report a recent decrease in early, confirmed HeartMate II LVAD thrombosis to historically observed levels, which is disparate to recent reports. While we identified several differences in clinical characteristics between patient groups, the issue of pump thrombosis is complex and multifactorial. Most importantly, our findings demonstrate the need for more granular analyses from collaborative efforts.
Intra-epidermal epithelioma.
Authors: PETER BERGER, RICHARD BAUGHMAN
Journal: British Journal of Dermatology (1974)

An intra‐epidermal epithelioma of 30 years duration invaded as squamous cell carcinoma. The tumour exhibited an unusual propensity for the production of parakeratotic debris. The potential of intra‐epidermal epithelioma for invasion is reviewed.
Abstract 17378: Familial Spontaneous Coronary Artery Dissection - Evidence for Genetic Susceptibility
Authors: Kashish Goel, Marysia Tweet, Timothy M Olson, Joseph J Maleszewski, Rajiv Gulati, Sharonne Hayes
Journal: Circulation (2014)

Background: Spontaneous coronary artery dissection (SCAD) typically presents as acute coronary syndrome in young women with no cardiovascular risk factors. It is associated with high morbidity and mortality, and is underdiagnosed. Despite this, risk factors and pathophysiology associated with SCAD are not completely understood. The objective of the present case series was to assess family history as a risk factor in patients with SCAD. Methods: We reviewed the medical records and questionnaires of 335 participants in the Mayo Clinic SCAD Registry for history of MI, SCAD or CAD in another family member. Coronary angiograms of all affected family members were reviewed by a senior interventional cardiologist. Results: We identified 4 familial cases of SCAD comprised of affected mother-daughter, identical twin sister, sister and aunt-niece pairs, implicating both recessive and dominant modes of inheritance. The mother-daughter pair also reported history of fatal MI in 3 maternal relatives including grandmother, great grandmother and great aunt. One of the affected twin sisters died of SCAD, which was confirmed on autopsy. None of the subjects had other potential risk factors for SCAD including extreme exercise, polycystic kidney disease, connective tissue disorder, peripartum status or diagnosed non-coronary fibromuscular dysplasia. The details of their demographics, risk factors, presentation, location of SCAD and management are presented in the table. Conclusions: This series is the first to identify a familial association in SCAD suggesting a genetic predisposition. Recognition of SCAD as a heritable disorder has implications for at-risk family members and furthers our understanding of the pathophysiology of this complex disease. Whole exome sequencing in these families provides a unique opportunity to identify the molecular underpinnings of SCAD susceptibility.
Assessing the severity of mitral stenosis.
Authors: P Gezerlis, G Scampardonis
Journal: Circulation (1978)

EDITORties of relaxed myocardium.Clearly, our study was concerned with LV chamber compliance (derived from diastolic pressure-volume data), not cardiac muscle stiffness (which is derived from myocar- dial stress-strain data).Secondly, while LV diastolic pressure-volume data may be fit by several equations, we selected a simple exponential: P = bekV.The k value is the slope of a log pressure-volume line; thus, k may be con-
Abstract 4334: Greater resistance of mutant p53 tumor cells to hypoxia or chloroquine with glucose or pyruvate supplementation is diminished under glucose starvation
Authors: Manuel Rieber
Journal: Cancer Research (2014)

Abstract BACKGROUND. Poorly vascularized solid tumors are exposed to regions of low oxygen and glucose deprivation. These restrictions may promote either defensive autophagy or cell death through excessive reactive oxygen species (ROS), mediated by activated NADPH oxidases (NOX) which transport electrons from NADPH on the cytoplasmic side of plasma membranes to reduce molecular oxygen at the extracellular space, increasing superoxide anion radical (O2•-). .OBJECTIVES. To investigate in genetically-matched human melanoma cells with wt or mutant p53, responses to: a) autophagy inhibitor chloroquine and to glucose-lowering metformin or to hypoxia in glucose-supplemented medium; b) pyruvate in glucose-free medium under normoxia or hypoxia; c) sub-physiological glucose. EXPERIMENTAL. Responses to normoxia or hypoxia were assesed by live-dead fluorometric assays, or by crystal violet staining of surviving cells. Mechanisms influencing response to glucose limitation were studied by specific immune blotting. RESULTS. Lower susceptibility to chloroquine ± metformin involving greater basal AMPK activation was seen in physiological 5 mM glucose in mutant p53 cells. These cells were also preferentially protected from prolonged hypoxia by glucose supplementation or by pyruvate supplementation of glucose-free medium under normoxia, but not under hypoxia. Sub-physiological glucose without pyruvate induced apoptosis-associated PARP cleavage irrespective of p53 status. However, treatment with impermeable exogenous superoxide dismutase (SOD) to remove extracellular superoxide signalling across cell membranes, preferentially counteracted PARP cleavage only in wt p53 cells with lower LDHA expression after 48 hr in 2.5 mM glucose. CONCLUSIONS. Glucose availability increases resistance to hypoxia or to chloroquine ± metformin in mutant p53 cells. However, glucose starvation promotes toxicity linked to extracellular (O2•-), preferentially in mutant p53 cells. Citation Format: Manuel Rieber. Greater resistance of mutant p53 tumor cells to hypoxia or chloroquine with glucose or pyruvate supplementation is diminished under glucose starvation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4334. doi:10.1158/1538-7445.AM2014-4334
Abstract 12603: Global T1 Mapping and Late Gadolinium Enhancement Cardiac MR in Myocardial Fibrosis Compared with Amyloid Cardiomyopathy
Authors: Garima Arora, Chimela Ohaji, Michael LaValley, Yansong Zhao, John L Berk, Vaishali Sanchorawala, Wilson S Colucci, David C Seldin, Frederick L Ruberg
Journal: Circulation (2012)

Background: Myocardial fibrosis is a feature of non-ischemic cardiomyopathy (NICM) and can be identified in approximately 25-40% of cases by cardiac MR (CMR) with late gadolinium enhancement (LGE) ...