tbuckley/cabot-search huggingface dataset:
Sex Differences in Implantable Cardioverter-Defibrillator Outcomes: Findings From a Prospective Defibrillator Database
Authors: Derek R. MacFadden, Eugene Crystal, Andrew D. Krahn, Iqwal Mangat, Jeffrey S. Healey, Paul Dorian, David Birnie, Christopher S. Simpson, Yaariv Khaykin, Arnold Pinter, Kumaraswamy Nanthakumar, Andrew J. Calzavara, Peter C. Austin, Jack V. Tu, Douglas S. Lee
Journal: Annals of Internal Medicine (2012)

Background: Sex differences in the use and outcomes of implantable cardioverter-defibrillators (ICDs) have not been fully studied. Objective: To examine potential sex differences in ICD implantation and device outcomes. Design: Health payer–mandated, prospective study of patients referred for ICD implantation, with comprehensive, longitudinal follow-up for complications, deaths, and device outcomes. Setting: 18 ICD implantation and follow-up centers in Ontario, Canada. Patients: 6021 patients (4733 men) referred for ICD implantation from February 2007 to July 2010. Measurements: Multivariate-adjusted ICD implantation rate, complications up to day 45, multivariate-adjusted complications, device outcomes (including appropriate shocks and therapies), and deaths occurring during 1-year follow-up. Results: Rates of ICD implantation were similar in men and women (relative risk, 0.99 [95% CI, 0.97 to 1.02]; P = 0.60). However, women were significantly more likely to experience major complications by 45 days (odds ratio, 1.78 [CI, 1.24 to 2.58]; P = 0.002) and 1 year (hazard ratio [HR], 1.91 [CI, 1.48 to 2.47]; P < 0.001) after implantation. Occurrence of any major or minor complication was also increased in women at both 45-day follow-up (odds ratio, 1.50 [CI, 1.12 to 2.00]; P = 0.006) and 1-year follow-up (HR, 1.55 [CI, 1.25 to 1.93]; P < 0.001). After implantation, women were less likely than men to receive appropriate ICD shock (HR, 0.69 [CI, 0.51 to 0.93]; P = 0.015) or appropriate therapy via shock or antitachycardia pacing (HR, 0.73 [CI, 0.59 to 0.90]; P = 0.003). Total mortality among defibrillator recipients did not differ between men and women (HR, 1.00 [CI, 0.64 to 1.55]; P = 0.99). Limitation: The differential effects of sex on prereferral events were not examined. Conclusion: Although ICD implantation rates were similar after referral to an electrophysiologist, women who underwent ICD implantation had greater risks for complications and were less likely to experience appropriate ICD-delivered therapies than men. Primary Funding Source: Canadian Institutes of Health Research and Ontario Ministry of Health and Long-Term Care.
Exome sequencing reveals germline NPAT mutation as a candidate risk factor for Hodgkin lymphoma
Authors: Silva Saarinen, Mervi Aavikko, Kristiina Aittomäki, Virpi Launonen, Rainer Lehtonen, Kaarle Franssila, Heli J. Lehtonen, Eevi Kaasinen, Peter Broderick, Jussi Tarkkanen, Barbara J. Bain, Frédéric Bauduer, Ali Ünal, Anthony J. Swerdlow, Rosie Cooke, Markus J. Mäkinen, Richard Houlston, Pia Vahteristo, Lauri A. Aaltonen
Journal: Blood (2011)
'Fresh Produce Initiative' for Imports Proposed
Authors: Charles Marwick
Journal: JAMA (1997)

TO IMPROVE the safety of imported food, the US government is reaching out to the farm. Plans are being developed to inspect the production sites of fruits and vegetables that come to the United States from abroad as thoroughly as such suppliers are examined in this country.  The effort is to ensure food safety at the production level, not just at the import point. If the administration's plans are realized, produce from a country with an inferior food safety system will be banned. This is a fundamental change from current efforts, in which suspect foods are seized at the port of entry.  The move comes in the wake of repeated occurrences of foodborne illness from imports and at a time when importation of foods into the United States has been growing rapidly. One estimate is that it has doubled in the past decade. The list of outbreaks of disorders caused
PWE-100 Repeat two week wait referrals for suspected colorectal cancer
Authors: P G Vaughan-Shaw, J Cutting, N R Borley, J M Wheeler
Journal: Gut (2012)

<h3>Introduction</h3> The two week-wait pathway for suspected colorectal cancer (CRC2ww) ensures prompt review and investigation of patients with symptoms concerning for malignancy. Previous investigation of such patients does not preclude future repeat referral yet may not represent efficient use of limited clinic time or diagnostic services. This study aims to evaluate the incidence and outcome of repeat CRC2ww referrals. <h3>Methods</h3> A retrospective review of all CRC2ww referrals to our unit over a 4-year period was conducted. Patients with previous CRC2ww referrals were identified from a hospital database. Referral indication and outcome for all referrals was collected. <h3>Results</h3> 2731 CRC2ww referrals were made between July 2007 and July 2011, median age 72 (19–102), 1179 (43%) male. 273 cancers were identified including 212 colorectal cancers. 121 referrals were repeat referrals, with 77 made prior to July 2007, and a median 1087.5 (35–2709) days between initial and repeat referrals. Referral indication was the same in 55 (47%) cases. When compared to unique referrals, repeat referral were associated with increased age (79 years vs 71 years, p&lt;0.0001) and increased proportion of females (69% vs 56%, p=0.0048). Six cancers, including two CRC, were identified following repeat referral with a median 1511.5 (477–1988) days between initial and repeat referrals. There was no statistical difference in cancer detection between unique or repeat referrals (5.2% vs 10.4%, p=0.07). <h3>Conclusion</h3> Repeat referrals comprise a small proportion of all CRC2ww referrals. Such patients are older and more commonly female. However, cancer detection is not significantly lower in this cohort when compared to those not previously referred. Historical referral or investigation should not preclude future CRC2ww referrals and such patients should be investigated to the same extent as unique referrals. <h3>Competing interests</h3> None declared.
Meeting Report: Translational Research at the Aging and Cancer Interface
Authors: Christopher C. Benz, Judith Campisi, Harvey J. Cohen, William B. Ershler, Irmgard Irminger-Finger
Journal: Cancer Research (2007)

AACR Special Conferences are designed to identify important areas in cancer research and provide a forum for exploring them in-depth. The recent Special Conference on “Translational Research at the Aging and Cancer Interface,” which was held in San Diego, CA from February 20 to 23, 2007, was the
Prospective Payment for Physician Services
Authors: Steven R. Lowenstein
Journal: JAMA (1985)

IN THE near future Congress is expected to begin formal consideration of  diagnosis-related groups (DRGs). The debate will undoubtedly prove contentious and controversial, as policymakers, physicians, and economists confront a number of important questions: Will extending DRGs to cover physician payments actually save money? Will DRGs provide fair and equitable reimbursement for physicians? Will physicians circumvent the system by pursuing the counterproductive incentives inherent in the DRGs? What will happen to quality of patient care and access to services? This last question is particularly vexing; how will quality and accessibility of care be preserved, even as physicians may receive less for their work and perform fewer services for patients? This article examines the potential impact of a physician DRG system on one important clinical activity that has often been equated with good quality medical care—the referral of patients for consultations.  Background  Efforts to curb the alarming escalation of Medicare
ORGANIC TUBERCULOSIS IN MAN ANALYZED FROM POSTMORTEM AND EXPERIMENTAL DATA
Authors: H. J. CORPER
Journal: JAMA (1927)

Probably the three most striking characteristics of tuberculosis as seen in man at postmortem are its predominant pulmonary localization, its extension bronchogenically by aspiration in the lung, and evidences of its variegated hematogenous dissemination. The predominant pulmonary disease has been attributed in the past to the importance, in the majority of the cases, of the respiratory tract as the route of infection in tuberculosis 1 and to the filtering action of the lungs, supposedly called into play frequently, especially in infancy and childhood, when infection is believed to occur through the alimentary tract. 2 In tuberculosis, especially in childhood, the lymphatic system has been considered to assume importance, 3 and Krause, 4 on the basis of extensive studies in the guinea-pig and rabbit, considers intrapulmonary differences of lymphatic tissue, blood supply and lymph flow decisive in determining the characteristic differences of pulmonary involvement in these two species. Deposition of the
Sexual Dysfunction in Women With Type 1 Diabetes
Authors: Paul Enzlin, Raymond Rosen, Markus Wiegel, Jeanette Brown, Hunter Wessells, Patricia Gatcomb, Brandy Rutledge, Ka-Ling Chan, Patricia A. Cleary
Journal: Diabetes Care (2009)

This study aimed to investigate the prevalence and risk factors associated with sexual dysfunction in a well-characterized cohort of women with type 1 diabetes.The study was conducted in women enrolled in the long-term Epidemiology of Diabetes Interventions and Complications (EDIC) study, a North American study of men and women with type 1 diabetes. At year 10 of the EDIC study, 652 female participants were invited to complete a validated self-report measure of sexual function, standardized history and physical examinations, laboratory testing, and mood assessment.Of the sexually active women with type 1 diabetes in the EDIC study, 35% met criteria for female sexual dysfunction (FSD). Women with FSD reported loss of libido (57%); problems with orgasm (51%), lubrication (47%), and arousal (38%); and pain (21%). Univariate analyses revealed a positive association between FSD and age (P = 0.0041), marital status (P = 0.0016), menopausal status (P = 0.0019), microvasculopathy (P = 0.0092), and depression (P = 0.0022). However, in a multivariate analysis, only depression (P = 0.004) and marital status (P = 0.003) were significant predictors of FSD.FSD is common in women with type 1 diabetes and affects all aspects of sexual function and satisfaction. Depression is the major predictor of sexual dysfunction in women with type 1 diabetes. These findings suggest that women with type 1 diabetes should be routinely queried about the presence of sexual dysfunction and possible co-association with depression.
Systemic effects of inhaled corticosteroids are milder in asthmatic patients than in normal subjects
Authors: L FABBRI
Journal: Thorax (2001)

Inhaled glucocorticosteroids are the first line anti-inflammatory agents for the long term treatment of asthma.1 2 They are also frequently prescribed in chronic obstructive pulmonary disease (COPD),3 even if their efficacy in this condition is still controversial.4 

The inhalatory mode of administration maximises the delivery to the airways and minimises the systemic delivery of glucocorticosteroids, increasing the therapeutic ratio.5 However, long term treatment of asthma6 and COPD7 with inhaled corticosteroids is associated with a significant risk of dose related systemic adverse events. This risk is particularly worrying in patients with moderate to severe asthma who require continuous treatment with high dose inhaled steroids to keep the disease under control and to prevent exacerbations, and who also require recurrent cycles of systemic glucocorticosteroids to treat exacerbations.2 3The biomarkers most frequently used to assess systemic availability of glucocorticosteroids are serum cortisol, urinary cortisol and its metabolites, and serum osteocalcin. The most worrying potential systemic effects are osteoporosis, growth suppression, adrenal insufficiency, cataracts, and glaucoma.8 

Several studies have assessed the systemic activity of inhaled steroids by looking at short term effects in normal subjects and/or mild asthmatics, with the assumption that results obtained in normal subjects could be transferred to more obstructed subjects such …
Rebound hypoxaemia after administration of oxygen in an acute exacerbation of chronic obstructive pulmonary disease
Authors: B. Kane, P. M. Turkington, L. S. Howard, A. G. Davison, G. J. Gibson, B. R. O'Driscoll
Journal: BMJ (2011)

Abrupt removal of high concentration oxygen in chronic obstructive pulmonary disease may produce life threatening hypoxaemia
Problems Are for Solving
Authors: Walter C. Bornemeier
Journal: JAMA (1972)

Among the problems that beset the medical profession, I shall consider the following: The number of doctors—in many areas, no doctor. The supply of family physicians—only 22% of doctors are generalists, mostly in older age groups. Maldistribution—even the rural rich and many affluent neighborhoods face scarcities. The hospital outpatient department as a primary care center at night and on weekends. The disproportion between specialty training programs, medical graduates, and community needs. Compensation of interns and residents. What are the solutions and what is being done? Almost four years ago, the American Medical Association, recognizing that a 7,500 doctor gain per year was not enough, held a meeting with the officers of the Association of American Medical Colleges. From that meeting came a statement that medical school enrollment should be increased to the point where every qualified applicant could be admitted. At that time there
Splanchnic and renal extraction of circulating type III procollagen aminoterminal propeptide in patients with normal liver function and in patients with alcoholic cirrhosis
Authors: Kirsten D. Bentsen, Jens H. Henriksen, Flemming Bendtsen, Kim Hørslev-Petersen, Ib Lorenzen
Journal: Hepatology (1990)

Splanchnic and renal extraction of circulating aminoterminal propeptide of type III procollagen and related antigens were studied in 12 patients with normal liver function and in 19 patients with alcoholic cirrhosis during catheterization. Type III procollagen peptide in serum was measured in two assays: the Type III Procollagen Peptide Radioimmunoassay Kit, a new assay that selectively determines the intact propeptide (and larger type III propeptide–holding antigens) and the Type III procollagen Fab assay that measures both the intact propeptide and the smaller fragments that quantitatively dominate in serum. A significant decrease in the concentration of the intact propeptide between the artery and the hepatic vein was found in the group with normal liver function (p &lt; 0.01) and in patients with cirrhosis (p &lt; 0.01). In patients with cirrhosis, however, the splanchnic extraction ratio of the intact propeptide (median = 0.04, range = –0.03 to 0.16) was significantly lower than in patients with normal liver function (median = 0.17, range = 0.05 to 0.36, p. &lt; 0.01). The concentration of the intact propeptide in the hepatic vein was positively correlated to hepatic pressure (n = 18, r = 0.51, p &lt; 0.05) and inversely correlated to indocyanine green clearance (n = 15, r = –0.61, p &lt; 0.05). No splanchnic extraction could be demonstrated in the Type III propeptide Fab assay. A significant renal extraction was found in the Fab assay, but not in Type III Procollagen Peptide Radioimmunoassay Kit. Similar extraction ratios were observed in both healthy patients (median = 0.11, range = 0.00 to 0.21) and cirrhotic patients (median = 0.14, range = 0.06 to 0.22). Thus intact circulating type III procollagen peptide is extracted in the liver, and the extraction ratio is decreased in alcoholic cirrhosis. Smaller type III procollagen peptide–related antigens are extracted from the circulation by the kidneys.(HEPATOLOGY 1990;11:957–963.).
Enhanced Tumorigenicity, Melanogenesis, and Metastases of a Human Malignant Melanoma After Subdermal Implantation in Nude Mice
Authors: I. Cornil, S. Man, B. Fernandez, R. S. Kerbel
Journal: JNCI Journal of the National Cancer Institute (1989)

Transplantation of human tumors into the organ or tissue of their origin (orthotopic transplantation) in nude mice can result in significant enhancement of tumor growth and metastases, compared with se (ectopic) transplantation. Because melanocytes are normally found in the epidermal-dermal junction, intradermal inoculation of melanoma cells might be expected to improve their potential for malignant growth as xenografts. The purpose of our study was to examine this possibility. We found that because mouse epidermis and dermis are so thin, it was not possible to inject a bolus of tumor cells intradermally; instead the cells were actually deposited in the most superficial layer of the subcutis (i.e., subdermally). We evaluated the behavior of cells from a human melanoma cell line after sc or subdennal inoculation into National Institutes of Health Swiss athymic nude mice. The cells used were from (2) the predominantly amelanotic human malignant melanoma cell line MeWo, originally established from a melanotic lymph node metastasis, and (2) two Me Wo variants resistant to wheat germ agglu-tinin (WGAr), which were selected for altered malignant capacities. Whereas 5×105 MeWo cells were required to achieve 100% tumor take with sc injection, only 2×104 cells were required with subdermal inoculation. Subder-mal injection of the MeWo cell resulted in the development of highly melanotic and nonencapsulated primary tumors, which grew quickly into the dermis and epidermis and metas-tasized at high frequency to draining lymph nodes. In contrast, the tumors that developed after sc injection were found in the deepest layer of the subcutis and were predominantly amelanotic and encapsulated; they rarely metastasized to lymph nodes. Neither of the WGAr variants, called 70-W and 3S5, displayed such drastic changes in growth behavior after subdermal inoculation. These results suggest that the subdermis, although not a perfect orthotopic site for a melanoma implant, may be more favorable and appropriate than the deep subcutis. In some cases, the subdermis may facilitate or induce the expression of phenotypic traits characteristic of human malignant melanomas in their natural host, and it may enhance the success rates of transplantation of such tumors in nude mice. [J Natl Cancer Inst 81:938-944, 1989]
Characterization of the myotonic dystrophy region predicts multiple protein isoform–encoding mRNAs
Authors: G. Jansen, M. Mahadevan, C. Amemiya, N. Wormskamp, B. Segers, W. Hendriks, K. O'Hoy, S. Baird, L. Sabourin, G. Lennon, P.L. Jap, D. Iles, M. Coerwinkel, M. Hofker, A. V. Carrano, P. J. de Jong, R. G. Korneluk, B. Wieringa
Journal: Nature Genetics (1992)
Low-grade Vesicoureteral Reflux Variability in Grade on Sequential Radiographic and Nuclear Cystograms
Authors: MICHAEL J. GELFAND, JANET L. STRIFE, VICTORIA S. HERTZBERG
Journal: Clinical Nuclear Medicine (1991)

Paired voiding cystourethrogram (VCU) and nuclear cystogram (NC) studies in 68 children with vesicoureteral reflux (VUR) were analyzed to determine the variability of VUR on sequential studies. Sequential paired examinations included 82 studies where a VCU was followed by a repeat VCU study and 128 studies where a VCU was followed by a NC study. Grade I VUR on the initial VCU was difficult to duplicate on repeat cystography, regardless of the follow-up modality. When the initial VCU showed no VUR, 20% of follow-up studies demonstrated VUR. Follow-up VCU and NC studies showed similar results in detecting increases and decreases in the grade of VUR. Low-grade VUR may be intermittent, and clinical therapeutic decisions should take this variability into account.
Rho-Kinase Inhibitor Improves Increased Vascular Resistance and Impaired Vasodilation of the Forearm in Patients With Heart Failure
Authors: Takuya Kishi, Yoshitaka Hirooka, Akihiro Masumoto, Koji Ito, Yoshikuni Kimura, Kosuke Inokuchi, Tatsuya Tagawa, Hiroaki Shimokawa, Akira Takeshita, Kenji Sunagawa
Journal: Circulation (2005)

Background— Rho-kinase is suggested to have an important role in enhanced vasoconstriction in animal models of heart failure (HF). Patients with HF are characterized by increased vasoconstriction and reduced vasodilator responses to reactive hyperemia and exercise. The aim of the present study was to examine whether Rho-kinase is involved in the peripheral circulation abnormalities of HF in humans with the Rho-kinase inhibitor fasudil. Methods and Results— Studies were performed in patients with HF (HF group, n=26) and an age-matched control group (n=26). Forearm blood flow was measured with a strain-gauge plethysmograph during intra-arterial infusion of graded doses of fasudil or sodium nitroprusside. Resting forearm vascular resistance (FVR) was significantly higher in the HF group than in the control group. The increase in forearm blood flow evoked by fasudil was significantly greater in the HF group than in the control group. The increased FVR was decreased by fasudil in the HF group toward the level of the control group. By contrast, FVR evoked by sodium nitroprusside was comparable between the 2 groups. Fasudil significantly augmented the impaired ischemic vasodilation during reactive hyperemia after arterial occlusion of the forearm in the HF group but not in the control group. Fasudil did not augment the increased FVR evoked by phenylephrine in the control group significantly. Conclusions— These results indicate that Rho-kinase is involved in increased FVR and impaired vasodilation of the forearm in patients with HF.
GlaxoSmithKline is fined record $3bn in US
Authors: B. Roehr
Journal: BMJ (2012)

GlaxoSmithKline has agreed to plead guilty and pay $3bn (£2bn; €2.4bn) in penalties for unlawful promotion of prescription drugs, failure to report safety data, and false price reporting.

It also signed a 123 page corporate integrity agreement with the US Department of Justice that regulates its activity for the next five years.1

The fine is the largest on record imposed on a drug company in the United States and follows closely on the heels of another huge penalty, $1.6bn, levied on Abbott Laboratories in May for its marketing of valproic acid.2

GSK’s agreement covers several of the its leading drugs. It illegally promoted the antidepressant paroxetine for treating patients under the age of 18, even though the Food and Drug Administration never approved the drug for that age group. The company also created “misleading” journal articles claiming efficacy of paroxetine in that population, when in fact “the study failed to demonstrate efficacy,” the justice department said in its statement, and it hid trials that …
RETRACTED: γ-Cleavage-Independent Functions of Presenilin, Nicastrin, and Aph-1 Regulate Cell-Junction Organization and Prevent Tau Toxicity In Vivo
Authors: Laura E. Doglio, Ritu Kanwar, George R. Jackson, Mar Perez, Jesús Avila, Colin Dingwall, Carlos G. Dotti, Mark E. Fortini, Fabián Feiguin
Journal: Neuron (2006)

Genetic analysis of familial Alzheimer's disease has revealed that mutations in the gamma-secretase enzyme presenilin promote toxic Abeta secretion; however, presenilin mutations might also influence tau hyperphosphorylation and neurodegeneration through gamma-secretase-independent mechanisms. To address this possibility and determine whether other components of the gamma-secretase complex possess similar regulatory functions, we analyzed the roles of presenilin, nicastrin, and aph-1 in a Drosophila model for tau-induced neurodegeneration. Here, we show that presenilin and nicastrin prevent tau toxicity by modulating the PI3K/Akt/GSK3beta phosphorylation pathway, whereas aph-1 regulates aPKC/PAR-1 activities. Moreover, we found that these transmembrane proteins differentially regulate the intracellular localization of GSK3beta and aPKC at cell junctions. Inhibition of gamma-secretase activity neither interfered with these kinase pathways nor induced aberrant tau phosphorylation. These results establish new in vivo molecular functions for the three components of the gamma-secretase complex and reveal a different mechanism that might contribute to neuronal degeneration in Alzheimer's disease.