tbuckley/cabot-search huggingface dataset:
Mental Health Act: definition of severe mental impairment and mental impairment and its implications.
Authors: T H Singh
Journal: BMJ (1984)

SIR,-In the leading article on antibiotic resistance in Serratia marcescens we were surprised to find no mention of the usefulness of ceftazidime.This third generation cephalosporin is now accepted to be useful in the treatment of serious infections caused by Gram negative organisms, including S mar- cescens.1We have found S marcescens isolated from patients in this hospital to be universally sensitive to ceftazidime, with no emergence of resistance to this agent, either during treat- ment or in subsequent isolates.Indeed, two patients who received two seven day courses of ceftazidime with apparent success had undergone renal transplantation.The urine of these patients remained sterile for periods ranging from four weeks to four months.It is also of interest that we have been unable to show the faecal carriage of S marcescens in these patients and to note that they had both received prior aminoglycoside treatment and that the organisms had subsequently become resistant to these agents.Our experience, that S marcescens remains sensitive to ceftazidime after its use, differs from that of others (3 December, p 1701)2 but this may be a reflection of other variables, such as use of antibiotics, which may affect the way in which resistant organisms emerge.
Mutations in the protein kinase A R1α regulatory subunit cause familial cardiac myxomas and Carney complex
Authors: Mairead Casey, Carl J. Vaughan, Jie He, Cathy J. Hatcher, Jordan M. Winter, Stanislawa Weremowicz, Kate Montgomery, Raju Kucherlapati, Cynthia C. Morton, Craig T. Basson
Journal: Journal of Clinical Investigation (2000)

Cardiac myxomas are benign mesenchymal tumors that can present as components of the human autosomal dominant disorder Carney complex. Syndromic cardiac myxomas are associated with spotty pigmentation of the skin and endocrinopathy. Our linkage analysis mapped a Carney complex gene defect to chromosome 17q24. We now demonstrate that the PRKAR1α gene encoding the R1α regulatory subunit of cAMP-dependent protein kinase A (PKA) maps to this chromosome 17q24 locus. Furthermore, we show that PRKAR1α frameshift mutations in three unrelated families result in haploinsufficiency of R1α and cause Carney complex. We did not detect any truncated R1α protein encoded by mutant PRKAR1α. Although cardiac tumorigenesis may require a second somatic mutation, DNA and protein analyses of an atrial myxoma resected from a Carney complex patient with a PRKAR1α deletion revealed that the myxoma cells retain both the wild-type and the mutant PRKAR1α alleles and that wild-type R1α protein is stably expressed. However, in this atrial myxoma, we did observe a reversal of the ratio of R1α to R2β regulatory subunit protein, which may contribute to tumorigenesis. Further investigation will elucidate the cell-specific effects of PRKAR1α haploinsufficiency on PKA activity and the role of PKA in cardiac growth and differentiation.
Tobacco use among pediatric cancer patients: recommendations for developing clinical smoking interventions.
Authors: V L Tyc, M M Hudson, P Hinds, V Elliott, M Y Kibby
Journal: Journal of Clinical Oncology (1997)

The current status of tobacco use among young cancer patients and the acute and chronic complications associated with tobacco use in these patients is reviewed.Studies report that adolescent cancer survivors use tobacco as much as their peers who have never been treated for cancer, despite the adverse consequences of engaging in this unhealthy habit. Health care professionals have the opportunity and responsibility to incorporate tobacco counseling as a routine component of medical care delivery. Nurse/physician-delivered smoking interventions have been found to promote smoking cessation in adults, although little effort has been devoted to the development of similarly effective smoking interventions for pediatric cancer patients who smoke. Components of existing smoking prevention/cessation curricula from successful school-based interventions and physician-delivered smoking interventions can be adapted and tailored to pediatric cancer patients in medical settings. Smoking interventions that educate patients about their increased vulnerability to tobacco-related consequences, relative to their healthy peers, may have an enhanced impact. Guidelines for conducting a comprehensive assessment of tobacco use and implementing smoking interventions with pediatric cancer patients is provided. Strategies for modifying the cancer patient's perceived vulnerability to tobacco-related consequences is also discussed.
Prospective Study of the Efficacy of Breast Magnetic Resonance Imaging and Mammographic Screening in Survivors of Hodgkin Lymphoma
Authors: Andrea K. Ng, Judy E. Garber, Lisa R. Diller, Robyn L. Birdwell, Yang Feng, Donna S. Neuberg, Barbara Silver, David C. Fisher, Karen J. Marcus, Peter M. Mauch
Journal: Journal of Clinical Oncology (2013)

Current guidelines recommend breast magnetic resonance imaging (MRI) as an adjunct to mammography for breast cancer screening in female cancer survivors treated with chest irradiation at a young age, beginning 8 to 10 years after treatment. Prospective data evaluating its efficacy in female cancer survivors are lacking. This study sought to compare the sensitivity and specificity of breast MRI with those of mammography in women who received chest irradiation for Hodgkin lymphoma (HL).We enrolled 148 women treated with chest irradiation for HL at age ≤ 35 years who were > 8 years beyond treatment. Yearly breast MRI and mammogram were performed over a 3-year period. Sensitivity and specificity of the two screening modalities were compared.With the screening, 63 biopsies were performed in 45 women; 18 (29%) showed a malignancy. All but one of the screen-detected malignancies were preinvasive or subcentimeter node-negative breast cancers. After excluding first-screen MRI and mammogram, mammogram sensitivity was 68% as compared with 67% for MRI (P = 1.0). Sensitivity increased to 94% using both screening modalities. The specificities of mammogram alone, MRI alone, and both were 93%, 94%, and 90%, respectively.In contrast to women with genetic or familial risk, in HL survivors breast MRI was not more sensitive than mammogram for breast cancer detection. However, the two screening modalities complement each other in the detection of early cases of disease. Early diagnosis is particularly important in these patients, given the breast cancer treatment challenges in patients who have received prior cancer therapy.
Surfactant Protein A Recruits Neutrophils into the Lungs of Ventilated Preterm Lambs
Authors: BORIS W. KRAMER, ALAN H. JOBE, CINDY J. BACHURSKI, MACHIKO IKEGAMI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We tested the effects of surfactant protein A (SP-A) on inflammation and surfactant function in ventilated preterm lungs. Preterm lambs of 131 d gestation were ventilated for 15 min to initiate a mild inflammatory response, and were then treated with 100 mg/ kg recombinant human SP-C surfactant or with the same surfactant supplemented with 3 mg/kg ovine SP-A. Addition of SP-A to the SP-C surfactant did not change lung function. After 6 h of ventilation, cell numbers in the alveolar wash were 4.9 times higher in SP-A + SP-C-surfactant–treated animals. Cellular infiltrates consisted of neutrophils that produced less hydrogen peroxide than did cells from SP-C-surfactant–treated animals. Expression of adhesion molecules CD11b and CD44 was significantly greater after SP-A treatment, whereas the expression of CD14 was unchanged. Messenger RNAs (mRNAs) for the proinflammatory cytokines interleukin (IL)-1 β , IL-6, and IL-8, but not tumor necrosis factor- α , were increased in SP-A–treated lungs. Surfactant protein mRNAs and protein leakage into alveolar washes were not altered by SP-A, indicating that SP-A treatment produces no evidence of lung injury. The present study identifies an unanticipated role of SP-A in neutrophil recruitment in the lungs of preterm lambs.
Lung function after coronary artery surgery using the internal mammary artery and the saphenous vein.
Authors: S C Jenkins, S A Soutar, A Forsyth, J R Keates, J Moxham
Journal: Thorax (1989)

Lung volumes and arterial blood gas tensions in patients undergoing coronary artery surgery were compared in 77 patients given an internal mammary artery graft (group 1) and 33 patients given a saphenous vein graft only (group 2). Patients in both groups developed a severe restrictive ventilatory defect after surgery, more pronounced in those receiving an internal mammary artery graft. Mean (SEM) vital capacity in groups 1 and 2 was reduced to 36% (1.2%) and 45% (2.0%) of preoperative values on the second postoperative day (1.56 and 1.85 1 respectively), with some recovery by day 4 to 56% (1.2%) and 63% (2.1%) of preoperative values. The mean (SEM) arterial oxygen tension was 7.34 (0.13) kPa for group 1 and 7.46 (0.20) kPa for group 2 on day 2, rising to 8.39 (0.13) and 9.01 (0.23) kPa on day 4. Analgesic requirements were greater in the group receiving an internal mammary artery graft. Possible explanations for the differences between the effects of the two grafts include the higher frequency of pleurotomy, the placing of pleural drains, and additional surgical trauma when internal mammary artery grafts are used.
Referral and receipt of treatment for hepatocellular carcinoma in United States veterans: Effect of patient and nonpatient factors
Authors: Jessica A. Davila, Jennifer R. Kramer, Zhigang Duan, Peter A. Richardson, Gia L. Tyson, Yvonne H. Sada, Fasiha Kanwal, Hashem B. El-Serag
Journal: Hepatology (2013)

The delivery of treatment for hepatocellular carcinoma (HCC) could be influenced by the place of HCC diagnosis (hospitalization versus outpatient), subspecialty referral following diagnosis, as well as physician and facility factors. We conducted a study to examine the effect of patient and nonpatient factors on the place of HCC diagnosis, referral, and treatment in Veterans Administration (VA) hospitals in the United States. Using the VA Hepatitis C Clinical Case Registry, we identified hepatitis C virus (HCV)-infected patients who developed HCC during 1998-2006. All cases were verified and staged according to Barcelona Clinic Liver Cancer (BCLC) criteria. The main outcomes were place of HCC diagnosis, being seen by a surgeon or oncologist, and treatment. We examined factors related to these outcomes using hierarchical logistic regression. These factors included HCC stage, HCC surveillance, physician specialty, and facility factors, in addition to risk factors, comorbidity, and liver disease indicators. Approximately 37.2% of the 1,296 patients with HCC were diagnosed during hospitalization, 31.0% were seen by a surgeon or oncologist, and 34.3% received treatment. Being seen by a surgeon or oncologist was associated with surveillance (adjusted odds ratio [aOR] = 1.47; 95% CI: 1.20-1.80) and varied by geography (1.74;1.09-2.77). Seeing a surgeon or oncologist was predictive of treatment (aOR = 1.43; 95% CI: 1.24-1.66). There was a significant increase in treatment among patients who received surveillance (aOR = 1.37; 95% CI: 1.02-1.71), were seen by gastroenterology (1.65;1.21-2.24), or were diagnosed at a transplant facility (1.48;1.15-1.90).Approximately 40% of patients were diagnosed during hospitalization. Most patients were not seen by a surgeon or oncologist for treatment evaluation and only 34% received treatment. Only receipt of HCC surveillance was associated with increased likelihood of outpatient diagnosis, being seen by a surgeon or oncologist, and treatment.
THE ENHANCEMENT OF CHLOROFORM-INDUCED PLASMA PROTEOLYTIC ACTIVITY BY EPSILON AMINOCAPROIC ACID
Authors: Virginia H. Donaldson, Oscar D. Ratnoff
Journal: The Journal of Experimental Medicine (1962)

The proteolytic activity in chloroform-treated plasma euglobulins has been attributed to plasmin. Plasmin can digest both casein and fibrin. Epsilon aminocaproic acid, which inhibits the activation of plasminogen, the precursor of plasmin, by streptokinase, urokinase, and tissue activators enhanced the development of casein hydrolytic activity in a mixture of chloroform and plasma euglobulins. Fibrinolytic activity was also enhanced, but this was evident only if the epsilon aminocaproic acid was removed from the chloroform-treated euglobulins prior to assay. The reasons for the paradoxical enhancement of chloroform-induced casein hydrolysis by euglobulins containing epsilon aminocaproic acid are unclear. However, studies of optimal pH, heat stability, and the effect of ionic strength on the activation of the precursor of this proteolytic enzyme do not differentiate it from plasminogen.
Selection Versus Demography: A Multilocus Investigation of the Domestication Process in Maize
Authors: M. I. Tenaillon
Journal: Molecular Biology and Evolution (2004)

The domestication of maize (Zea mays ssp. mays) from its wild ancestor (Zea mays ssp. parviglumis) led to a loss of genetic diversity both through a population bottleneck and through directional selection at agronomically important genes. In order to discriminate between those effects and to investigate the nature of the domestication bottleneck, we analyzed nucleotide diversity data from 12 chromosome 1 loci in parviglumis. We found an average loss of nucleotide diversity of 38% across genes, but this average was skewed downward by four putatively selected loci (tb1, d8, ts2, and zagl1). To better understand the domestication process, we used the coalescent with recombination to simulate bottlenecks under various lengths and population sizes. For each locus, we determine the likelihood of the observed data using three summary statistics: the number of segregating sites, an estimate of the population recombination parameter, and Tajima's D. Based on the eight neutrally evolving loci, a model with a bottleneck had a significantly higher likelihood than a model without one. The four putatively selected loci had significantly different likelihood optimums than the neutral loci, and this approach confirmed that ts2 and d8 were selected either during domestication or breeding. Overall, the best-fitting models had a bottleneck in which the population size and the bottleneck duration had a ratio of approximately 4- to approximately 5; for example, if the initial domestication event occurred over a 500-year period, the population size was roughly 2,000 to 2,500 individuals. However, this range did vary with the summary statistic used to assess the fit of simulations to data. In this context, Tajima's D performed poorly as a goodness-of-fit statistic, probably because Z. mays ssp. parviglumis has a frequency spectrum that is significantly skewed toward low-frequency variants. Finally, we found that demography is unlikely to account for the previously observed positive correlation between nucleotide diversity and the population-recombination parameter in maize, leaving this observation difficult to interpret.
Comparison of sports medicine, public health and exercise promotion between bidding countries for the FIFA World Cup in 2018
Authors: Jessica Joan Orchard, John William Orchard, Timothy R Driscoll
Journal: British Journal of Sports Medicine (2010)

To ascertain whether it is possible to assess countries bidding for international sporting events based on public health and sports medicine criteria. In particular, the authors undertook this exercise for countries bidding for the 2018 Fédération Internationale de Football Association (FIFA) Football World Cup (2018 World Cup).A scorecard framework approach to pose and answer nine relevant questions. Questions were answered using Medline-listed references (where possible) and internet research.England scored the highest overall, largely due to its sports medicine training programme and recognition, and funding of treatment for sports injuries. The Netherlands/Belgium scored highly in the questions relating to public health expenditure, Australia was very strong in sports medicine research, and Japan was the best of the bidding countries in terms of having a lower prevalence of overweight and obese people.It is possible to assess countries bidding for international sporting events based on their performance with respect to sports medicine, physical activity and health promotion criteria. Bodies organising major sporting events such as FIFA and the International Olympic Committee may wish to consider making public health measures part of the bidding criteria for hosting these events.
Induction of Apoptosis and T Helper 2 (Th2) Responses Correlates with Peptide Affinity for the Major Histocompatibility Complex in Self-reactive T Cell Receptor Transgenic Mice
Authors: C.I. Pearson, W. van Ewijk, H.O. McDevitt
Journal: The Journal of Experimental Medicine (1997)

Multiple sclerosis is an autoimmune disease thought to be mediated by CD4+ T helper cells (Th). Experimental autoimmune encephalomyelitis is a rodent model of multiple sclerosis and has been used extensively to explore a variety of immunotherapies using soluble protein or peptide antigens. The underlying mechanisms of such therapy have been attributed to induction of T cell anergy, a switch in Th1 to Th2 responses, or peripheral deletion of autoreactive T cells. In this study, we have developed transgenic mice expressing a T cell receptor (TCR) specific for the NH2-terminal peptide Ac1-11 of the autoantigen myelin basic protein to explore the mechanism of soluble peptide therapy. T cells from these mice are highly skewed toward the CD4 population and have an abnormal thymic architecture, a phenomenon found in other TCR transgenic mice that exhibit a highly skewed CD4/CD8 ratio. Soluble Ac1-11 or the analogues Ac1-11[4A] or Ac1-11[4Y] (which bind to the major histocompatibility complex [MHC] class II molecule I-Au with increasing affinities) given intravenously activates T cells, rendering cells hyperresponsive in vitro for at least two days after injection. Concomitantly, T cells apoptose in the periphery, the degree of which correlates with the affinity of the peptide for the MHC. In addition, a shift in the T helper phenotype of the surviving T cells occurs such that the low affinity peptide, Ac1-11, induces primarily a Th1 response, whereas the highest affinity peptide, Ac1-11[4Y], induces primarily a Th2 type response. These data show that both the nature and the presumed number of the peptide–MHC complexes formed during specific peptide therapy affect both the degree of peripheral programmed cell death as well as the outcome of the T helper subset response in vivo, leading to amelioration of disease.
In adult acute nonlymphoblastic leukaemia extended maintenance chemotherapy has no benefit
Authors: Peter Jacobs, D. W. Dubovsky, Lucille Wood
Journal: American Journal of Hematology (1984)

Abstract Fifty‐two consecutive and previously untreated adults with nonlymphoblastic leukaemia underwent remission induction chemotherapy with a combination of the epipodophyllotoxin VP16‐213, cytosine arabinoside, and doxorubicin (Adriamycin). Complete remission was achieved in 23 of the 52 patients (44%) by means of a single course of therapy in 20 individuals, two courses in two, and three courses in one; median duration of complete remission was 48 weeks. Failure to achieve remission status was due to primary drug resistance in 13 patients (25%), and adequate trial of therapy was not possible in 16 patients (31%) owing to their late referral and accounts for the low remission rate. Individuals achieving complete remission were randomly assigned to receive either 6 (n = 8) or 15 months (n = 13) of maintenance therapy; respective median survival was 95 and 78 weeks (P &gt; 0.10). These data confirm previously reported results for complete remission induction with this three‐drug combination and fail to show any difference between short (6 months) and long (15 months) maintenance chemotherapy.
Cyclin-dependent kinase 5 activity is required for T cell activation and induction of experimental autoimmune encephalomyelitis
Authors: Tej K. Pareek, Eric Lam, Xiaojing Zheng, David Askew, Ashok B. Kulkarni, Mark R. Chance, Alex Y. Huang, Kenneth R. Cooke, John J. Letterio
Journal: The Journal of Experimental Medicine (2010)

Cyclin-dependent kinase 5 (Cdk5) is a ubiquitously expressed serine/threonine kinase. However, a requirement for Cdk5 has been demonstrated only in postmitotic neurons where there is abundant expression of its activating partners p35 and/or p39. Although hyperactivation of the Cdk5–p35 complex has been found in a variety of inflammatory neurodegenerative disorders, the potential contribution of nonneuronal Cdk5–p35 activity has not been explored in this context. We describe a previously unknown function of the Cdk5–p35 complex in T cells that is required for induction of experimental autoimmune encephalomyelitis (EAE). T cell receptor (TCR) stimulation leads to a rapid induction of Cdk5–p35 expression that is required for T lymphocyte activation. Chimeric mice lacking Cdk5 gene expression in hematopoietic tissues (Cdk5−/−C) are resistant to induction of EAE, and adoptive transfer of either Cdk5−/−C or p35−/− encephalitogenic lymphocytes fails to transfer disease. Moreover, our data reveal a novel mechanism involving Cdk5-mediated phosphorylation of the actin modulator coronin 1a on threonine 418. Cdk5-deficient lymphocytes lack this posttranslational modification of coronin 1a and exhibit defective TCR-induced actin polarization and reduced migration toward CCL-19. These data define a distinct role for Cdk5 in lymphocyte biology and suggest that inhibition of this kinase may be beneficial in the treatment of T cell–mediated inflammatory disorders.
BLOOD PRESSURE IN ELITE ATHLETES: A SYSTEMATIC REVIEW
Authors: HM Berge, CB Isern, E Berge
Journal: British Journal of Sports Medicine (2014)

Background High blood pressure (BP) is a leading cause of illness, and bilateral measurement of BP is recommended in IOC's preparticipation health examination. Still there is limited data on BP in elite athletes. Objective To describe blood pressure, prevalence of hypertension and subclinical organ damage (left ventricular hypertrophy) in elite athletes. Design Systematic review, using a comprehensive search strategy developed for PubMed. Setting We identified studies of BP in elite athletes, including only studies of ≥100 athletes. Of 2049 studies identified, only 40 studies met the inclusion criteria. Participants Elite athletes aged 18 to 35 years. Assessment of risk factors High BP; Left ventricular hypertrophy. Main outcome measurements Office and ambulatory BP; Prevalence of hypertension; Method of BP measurement; Associations between BP and left ventricular hypertrophy (determined by voltage criteria on ECG or left ventricular mass on echocardiography). Results Office BP was recorded from one to three times at each visit, and measurements were repeated at different time intervals in nine studies. Only one study measured BP in both arms, and only two studies measured ambulatory BP if office BP was high. Mean systolic BP varied from 112±11 mmHg to 138±7 mmHg and mean diastolic BP from 59±8 mmHg to 86±7 mmHg. Hypertension was not defined or defined differently, from ≥130/85 mmHg to ≥150/95 mmHg, and the prevalence of hypertension varied from 0 to 45%. Athletes of both genders and from different sports disciplines were mixed in half of the studies. Four studies showed an association between increased BP and left ventricular hypertrophy. Conclusions Definition and prevalence of hypertension and methods of BP measurement differed substantially between the studies, and only a few studies investigated the association between high BP and subclinical organ damage. Future studies should use standardised definitions and methods, and hypertension as a risk factor in athletes should be further investigated.