tbuckley/cabot-search huggingface dataset:
Population-Based Patterns and Predictors of Prostate-Specific Antigen Screening Among Older Men in the United States
Authors: Michael W. Drazer, Dezheng Huo, Mara A. Schonberg, Aria Razmaria, Scott E. Eggener
Journal: Journal of Clinical Oncology (2011)

Purpose For patients who elect to have prostate cancer screening, the optimal time to discontinue screening is unknown. Our objective was to describe rates and predictors of prostate-specific antigen (PSA) screening among older men in the United States. Methods Data were extracted from the population-based 2000 and 2005 National Health Interview Survey (NHIS). PSA screening was defined as a PSA test as part of a routine exam within the past year. Demographic, socioeconomic, and functional characteristics were collected, and a validated 5-year estimated life expectancy was calculated. Age-specific rates of PSA screening were determined, and sampling weight-adjusted multivariate regressions were fitted to determine predictors of screening among men age 70 years or older. Results The PSA screening rate was 24.0% in men age 50 to 54 years, and it increased steadily with age until a peak of 45.5% among age 70 to 74 years. Screening rates then gradually declined by age, and 24.6% of men age 85 years or older reported being screened. Among men age 70 years or older, screening rates varied by estimated 5-year life expectancy: rates were 47.3% in men with high life expectancies (≤ 15% probability of 5-year mortality), 39.2% in men with intermediate life expectancies (16% to 48% probability), and 30.7% in men with low life expectancies (&gt; 48% probability; P &lt; .001). In multivariate analysis, estimated life expectancy and age remained independently associated with PSA screening (P &lt; .001 for each). Conclusion Rates of PSA screening in the United States are associated with age and estimated life expectancy, but excessive PSA screening in elderly men with limited life expectancies remains a significant problem. The merits and limitations of PSA should be discussed with all patients considering prostate cancer screening.
Winter sports athletes: long-term effects of cold air exposure
Authors: Malcolm Sue-Chu
Journal: British Journal of Sports Medicine (2012)

Athletes such as skaters and skiers inhale large volumes of cold air during exercise and shift from nasal to mouth breathing. Endurance athletes, like cross-country skiers, perform at 80% or more of their maximal oxygen consumption and have minute ventilations in excess of 100 l/min. Cold air is always dry, and endurance exercise results in loss of water and heat from the lower respiratory tract. In addition, athletes can be exposed to indoor and outdoor pollutants during the competitive season and during all-year training. Hyperpnoea with cold dry air represents a significant environmental stress to the airways. Winter athletes have a high prevalence of respiratory symptoms and airway hyper-responsiveness to methacholine and hyperpnoea. The acute effects of exercise in cold air are neutrophil influx as demonstrated in lavage fluid and airway epithelial damage as demonstrated by bronchoscopy. Upregulation of pro-inflammatory cytokines has been observed in horses. Chronic endurance training damages the epithelium of the small airways in mice. Airway inflammation has been observed on bronchoscopy of cross-country skiers and in dogs after a 1100-mile endurance race in Alaska. Neutrophilic and lymphocytic inflammation with remodelling is present in bronchial biopsies from skiers. Repeated peripheral airway hyperpnoea with dry air causes inflammation and remodelling in dogs. As it is currently unknown if these airway changes are reversible upon cessation of exposure, preventive measures to diminish exposure of the lower airways to cold air should be instituted by all winter sports athletes.
MEMORANDUM ON THE TREATMENT OF INFECTED WOUNDS BY PHYSIOLOGICAL METHODS: (Drainage of Infected Tissues by Hypertonic Salt Solution, and Utilization of the Antibacterial Powers of the Blood Fluids and White Blood Corpuscles.)
Authors: A. E. Wright
Journal: BMJ (1916)

YDBar 793 ,TUNE_3, 119161 IMgDwIAL JO_.793_9. It is desirable that napihthalene-creosote powders hlould be supplied in sealed tins of a uniformly stmall size, or of sizes suitable for the immediate requirements of a convenient number of persons propo.sed to be treated at one time.10.In experiments with gases, sulplhur dioxide has maintained its reputation as thie most efficient gaseous insecticide, and all lice exposed -to an atmiosplhere of the gas die witllin five seconds.As ot-dinarily used for dis- infecting purposes and as a result of lack of penetration sulphur dioxide cannot be depended on to kill all lice in verminous clotlhing. 11.For the crnergency cleansing of clotlhing by means of petrol, immersion of thie verminous clothing in petrol reImains the inost suitable muetlhod.To secure the insecti- cidal action of the vapour of petrol a regulated oven would lhave to be employed.12. The superior value of certain chlorine derivatives of ethylene and ethane as insecticides and tlleir non-inflam- mable properties indicate their use in the cleansing of ver- nminonts heads.The desired result is obtained and irritant effect on the scalp is obviated wlhen the hair is gone over carefully witlh pieces of cotton-wool moistened witlh either trichllorethylene or tetrachlorethane.Tetrachlorethane, althjouglh less powerful than trichllorethylene, is very actively insecticidal, and is to be preferred to trichlor- ethylene on account of its less irritant properties.
The linear relation between oxygen consumption and pressure-volume area can be reconciled with the Fenn effect in dog left ventricle.
Authors: T Nozawa, Y Yasumura, S Futaki, N Tanaka, H Suga
Journal: Circulation Research (1989)

We studied the Fenn effect in 12 excised cross-circulated dog left ventricles in control contractility and in a contractility enhanced by dobutamine or depressed by propranolol. The additional oxygen consumption (Vo2) in an ejecting contraction compared with that found in an isovolumic contraction at a comparable end-systolic pressure was considered to constitute the cardiac Fenn effect. We examined whether this load-dependent Vo2 could be reconciled with the linear relation between Vo2 and pressure-volume area (PVA) common for both ejecting and isovolumic contractions that has so far been consistently observed and was presently confirmed. PVA is a specific area in the pressure-volume diagram, represents the total mechanical energy generated by each contraction, and consists of external mechanical work (EW) and mechanical potential energy. Because potential energy is common in the isovolumic and ejecting contractions producing the same end-systolic pressure, PVA of the ejecting contraction is greater by EW than that of the isovolumic contraction. Despite this difference in PVA by EW, the Vo2-PVA relation was always linear and load independent regardless of the isovolumic and ejecting contractions in a given heart in any given contractile state. By contrast, the upward convex Vo2-end-systolic pressure relation was higher for ejecting contractions than the downward convex Vo2-end-systolic pressure relation for isovolumic contractions in each contractile state. The difference of Vo2 between the ejecting and isovolumic contractions was proportional to EW at comparable end-systolic pressure. The slope of the additional Vo2 of ejecting contractions plotted against their EW had a slope close to the slope of the Vo2-PVA relation. Thus, the load-independent linear Vo2-PVA relation can be reconciled with the cardiac Fenn effect.
Association between polymorphism in p21(Waf1/Cip1) cyclin-dependent kinase inhibitor gene and human oral cancer.
Authors: R Ralhan, S Agarwal, M Mathur, B Wasylyk, A Srivastava
Journal: Clinical Cancer Research (2000)

The cyclin-dependent kinase inhibitor gene p21(Waf1/Cip1) plays a central role in inducing cellular growth arrest, terminal differentiation, and apoptosis. Alterations in this gene may adversely affect regulation of these processes and increase susceptibility for cancer. We have recently reported a novel polymorphism in the p21(Waf1/Cip1) gene in the Indian population and its association with esophageal cancer. An A-->G transition at codon 149 resulted in amino acid substitution from aspartate to glycine in the proliferating cell nuclear antigen binding COOH-terminal domain of p21(Waf1/Cip1) that may affect PCNA-p21(Waf1/Cip1) interactions, thereby affecting regulation of cellular proliferation, and may increase susceptibility for development of cancer. In a parallel study in our laboratory, we searched for putative p21(Waf1/Cip1) mutations in oral premalignant and malignant lesions. No somatic mutation was detected in exon 2 of p21(Waf1/Cip1). Interestingly, a codon 149 polymorphism variant (A-->G) was identified in 11 of 30 (37%) premalignant lesions (7 of 19 hyperplastic lesions and 4 of 11 dysplastic lesions) and 11 of 30 (37%) squamous cell carcinomas (SCCs). This codon 149 variant was also identified in paired lymphocytes of all of the patients with premalignant lesions and SCCs harboring the variant allele, suggesting the occurrence of a polymorphism. Lymphocyte DNA isolated from 50 unrelated age- and gender-matched healthy subjects was screened for this polymorphism. Seven of 50 (14%) normal controls harbored the A-->G codon 149 variant allele. Immunohistochemical analysis of p21(Waf1/Cip1) protein expression showed immunoreactivity in 19 of these 30 (63%) oral premalignant lesions and 16 of 30 (53%) SCCs. The most intriguing features of the study were: (a) the significant increase in frequency of this polymorphism not only in patients with oral SCCs (P = 0.038), but also in patients with premalignant lesions (P = 0.038), compared with normal controls; and (b) the significantly higher frequency of p21(Waf1/Cip1) variants (codon 149) in oral premalignant lesions (10 of 11 cases) and SCCs (11 of 11 cases) with wild-type p53 (P = 0.045) than in lesions with p53 mutations, suggesting that this polymorphism affects the p53 pathway and may play a vital role in oral tumorigenesis. Furthermore, overexpression of p21 protein in oral lesions harboring missense mutations in the p53 gene suggest a p53-independent role for p21 in the pathogenesis of oral cancer.
Nimotuzumab, an Antitumor Antibody that Targets the Epidermal Growth Factor Receptor, Blocks Ligand Binding while Permitting the Active Receptor Conformation
Authors: Ariel Talavera, Rosmarie Friemann, Silvia Gómez-Puerta, Carlos Martinez-Fleites, Greta Garrido, Ailem Rabasa, Alejandro López-Requena, Amaury Pupo, Rune F. Johansen, Oliberto Sánchez, Ute Krengel, Ernesto Moreno
Journal: Cancer Research (2009)

Overexpression of the epidermal growth factor (EGF) receptor (EGFR) in cancer cells correlates with tumor malignancy and poor prognosis for cancer patients. For this reason, the EGFR has become one of the main targets of anticancer therapies. Structural data obtained in the last few years have revealed the molecular mechanism for ligand-induced EGFR dimerization and subsequent signal transduction, and also how this signal is blocked by either monoclonal antibodies or small molecules. Nimotuzumab (also known as h-R3) is a humanized antibody that targets the EGFR and has been successful in the clinics. In this work, we report the crystal structure of the Fab fragment of Nimotuzumab, revealing some unique structural features in the heavy variable domain. Furthermore, competition assays show that Nimotuzumab binds to domain III of the extracellular region of the EGFR, within an area that overlaps with both the surface patch recognized by Cetuximab (another anti-EGFR antibody) and the binding site for EGF. A computer model of the Nimotuzumab-EGFR complex, constructed by docking and molecular dynamics simulations and supported by mutagenesis studies, unveils a novel mechanism of action, with Nimotuzumab blocking EGF binding while still allowing the receptor to adopt its active conformation, hence warranting a basal level of signaling.
Psychosocial Care of Adolescent and Young Adult Patients With Cancer and Survivors
Authors: Brad Zebrack, Sinéad Isaacson
Journal: Journal of Clinical Oncology (2012)

The delivery of quality care for adolescent and young adult (AYA) patients with cancer and survivors requires an understanding of the unique qualities of this group—the shared norms, attitudes, and beliefs that determine their behavior as well as the unique stresses they face on a day-to-day basis. All AYAs have typical concerns about being comfortable with who they are and who they want to become (identity development, including sexual identity), their bodies (body image), initiating intimate and emotional relationships, separating from parents, and making independent decisions about future goals such as career, higher education, and/or family (autonomy). Yet efforts of AYA patients with cancer and survivors to mature are often confounded by restrictions and limitations placed on them by their disease and treatment. This article promotes understanding of psychosocial challenges faced by AYAs when diagnosed with and treated for cancer. It reviews evidence-based psychosocial support interventions for AYAs with cancer and other life-threatening or chronic diseases, particularly the positive effects of peer support, technology-based interventions, and skill-based interventions. The article concludes with recommendations for clinical care that are intended to promote the ability of AYAs to cope with cancer.
Efficacy of Acellular Pertussis Vaccine in Early Childhood After Household Exposure
Authors: Heinz-J. Schmitt
Journal: JAMA (1996)

<h3>Objective.</h3> —To evaluate the efficacy of a three-dose primary vaccination with a diphtheria-tetanus tricomponent acellular pertussis vaccine against "typical" pertussis, defined as a spasmodic cough of 21 days or longer with confirmation of<i>Bordetella pertussis</i>infection by culture or serology. <h3>Design.</h3> —Passive monitoring for suspected first household (index) cases of typical pertussis in six areas in Germany comprising 22 505 children vaccinated with study vaccine at 3, 4, and 5 months of age. Blinded, prospective follow-up of household contacts of index cases for incidence and progression of pertussis. <h3>Setting.</h3> —Six areas in Germany with a high incidence of pertussis. <h3>Subjects.</h3> —Four hundred fifty-three households with index cases comprising 360 evaluable contacts eligible for analysis of vaccine efficacy. <h3>Main Outcome Measure.</h3> —Vaccine efficacy from attack rates of pertussis in household contacts classified by vaccination status. <h3>Results.</h3> —Of the 173 nonvaccinated household contacts, 96 developed typical pertussis, compared with seven of 112 contacts vaccinated with acellular pertussis vaccine. Vaccine efficacy was consequently calculated to be 88.7% (95% confidence interval, 76.6% to 94.6%). Protection did not wane until at least the time recommended for booster vaccination. None of the analyzed potential confounding factors—age, socioeconomic status, erythromycin treatment, household composition, center effect, and selection bias—influenced study results in favor of the vaccine. <h3>Conclusions.</h3> —Under conditions of intense household exposure, primary vaccination with acellular vaccine protected against pertussis until at least the time recommended for booster vaccination. The vaccine can be expected to be equally or more effective in settings with lower infectious pressure. (<i>JAMA</i>. 1996;275:37-41)
Congenital neutropenia: Studies of pathogenesis
Authors: Michael J. Chusid, Anthony V. Pisciotta, Rene J. Duquesnoy, Bruce M. Camitta, Peter A. Tomasulo
Journal: American Journal of Hematology (1980)

Congenital neutropenia (CN) was diagnosed in a five-month-old boy. A variety of studies was performed to define the pathogenesis of his disease. Opsonic antineutrophil antibodies wre present in his serum. Transfused normal granulocytes circulated poorly. Incubation of the patient's serum with normal granulocytes failed to alter their metabolic or functional activity. The patient's marrow demonstrated increased numbers of colony-forming units (CFUs) in vitro compared with control marrow. The patient's parents had low marrow CFU activity. The patient's serum and peripheral lymphocytes failed to inhibit normal marrow CFU activity. The patient's marrow did inhibit CFU growth of an HLA-identical-sibling's marrow in coculture. Histocompatibility studies demonstrated the HLA-B12 antigen in this patient, a histocompatibility marker previously associated with CN. These studies suggest some cases of CN are associated with a genetically transmitted marrow factor capable of suppressing myelopoiesis in normal marrow.
Exercise in osteoporosis
Authors: S. Shenoy
Journal: British Journal of Sports Medicine (2010)

Osteoporosis is a systemic disease characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in skeletal fragility and susceptibility to fractures (Consensus Report 1993). Decreased bone mass in the elderly arises because of the degradation of normal balance between bone resorption and bone formation observed in the young adult (Bass <i>et al</i> 1999 and Hansen <i>et al</i> 1991). Pharmacological treatment of osteoporosis entails the use of medications that favourably alter bone remodelling. Current strategies include the administration of antiresorptive agents to inhibit the elevated rate of resorption and the administration of anabolic agents that stimulate osteoblastic bone formation (Mc Dermott <i>et al</i> 2004) options that are extremely limited. Mechanical loading of the bone through the application of exercise has substantial potential to induce bone formation. Yet, studies exploring the use of exercise in humans for the purpose of increasing bone mass have met with mixed results (Turner <i>et al</i> 1994). This article explores the practical considerations for the use of exercise strategies in the enhancement of bone mass.
Rap2-JNK Removes Synaptic AMPA Receptors during Depotentiation
Authors: Yinghua Zhu, Daniel Pak, Yi Qin, Stefanie G. McCormack, Myung J. Kim, Joel P. Baumgart, Vanisree Velamoor, Yves P. Auberson, Pavel Osten, Linda van Aelst, Morgan Sheng, J. Julius Zhu
Journal: Neuron (2005)
Management of Prostate Cancer — Polling Results
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (2009)

In early December, we presented the case of a 63-year-old man with a rising prostate-specific antigen (PSA) level in Clinical Decisions,1 an interactive feature designed to assess how readers would manage a clinical problem for which there may be more than one appropriate treatment. The patient had no symptoms and was physically and sexually active. Biopsy of the prostate revealed adenocarcinoma with a Gleason score of 6 in 2 of 12 biopsy cores.Among the 3720 votes cast, 29% were for expectant management, 33% for radiotherapy, and 39% for radical prostatectomy. The votes that could be attributed to a continent . . .
Monitoring human tissues for toxic substances: a follow-up to the National Academy of Sciences (NAS) report.
Authors: J C Bailar
Journal: Environmental Health Perspectives (1995)

In 1991, the National Academy of Sciences (NAS) published a report, Monitoring Human Tissues for Toxic Substances, which presented a summary of thinking about the banking of human tissue specimens at the time the report was completed. The present article summarizes the findings and recommendations in the NAS report. Events have moved very rapidly since that time, but some history may be helpful in understanding how we have come to where we are today.
Psychological, social and health behaviour risk factors for deaths certified as asthma: a national case-control study
Authors: P M Sturdy
Journal: Thorax (2002)

Uncontrolled studies suggest that psychosocial factors and health behaviour may be important in asthma death.A community based case-control study of 533 cases, comprising 78% of all asthma deaths under age 65 years and 533 hospital controls individually matched for age, district and asthma admission date corresponding to date of death was undertaken in seven regions of Britain (1994-98). Data were extracted blind from anonymised copies of primary care records for the previous 5 years and non-blind for the earlier period.60% of cases and 63% of controls were female. The median age in both groups was 53. Cases had an earlier age of asthma onset, more chronic obstructive lung disease, and were more obese. 48% of cases and 42% of controls had a health behaviour problem; repeated non-attendance/poor inhaler technique was related to increased risk of death. Overall, 85% and 86%, respectively, had a psychosocial problem. Four psychosocial factors were associated with increased risk of death (psychosis, alcohol/drug abuse, financial/employment problems, learning difficulties) and two with reduced risk (anxiety/prescription of antidepressant drugs and sexual problems). While alcohol/drug abuse lost significance after adjustment for psychosis, other associations appeared independent of each other and of indicators of severity and co-morbidity. None of the remaining 13 factors including family problems, domestic abuse, bereavement, and social isolation were significantly related to risk of asthma death.There was an apparently high burden of psychosocial problems in both cases and controls. The associations between health behaviour, psychosocial factors, and asthma death are varied and complex with a limited number of factors showing positive relationships.
Immune Profiling of Tumors May Better Stage Early Cancers
Authors: G. Sinha
Journal: JNCI Journal of the National Cancer Institute (2015)

When immune cells infiltrate tumors in large numbers, patients do better. Now researchers aim to harness this immune response to predict outcomes. The Society for Immunotherapy of Cancer (SITC) in Milwaukee is coordinating an international effort to validate Immunoscore, an assay that quantifies this immune response. If added to the current tumor–node–metastasis (TNM) cancer staging system, it may help clinicians decide when to use additional therapy to treat early-stage cancer. Such immune profiling may also help hone immunotherapy by identifying patients more likely to respond. “Immunoscore will be used if it can be validated,” said Bernard Fox, Ph.D., head of the tumor immunology focus group at Oregon Health and Science University Cancer Institute in Portland and former SITC president. Researchers led by Jerome Galon, Ph.D., research director in the cancer immunology laboratory at Paris’s French National Institute of Health and Medical Research, proposed that profiling immune cells in and around tumors might help stage cancers after their own studies suggested that it could predict survival. Seventy-three percent of colorectal cancer patients with high densities of immune cells in and around their tumors survived for 5 years, compared with only 30% for patients with low densities (Science 2006;313: 1960–4). Further research showed that quantifying densities of two lymphocyte populations—cytotoxic CD8 T cells and memory T cells expressing CD45RO antigen, CD3 and CD8 T cells, or CD3 and memory CD45RO T cells—both in the tumor core and in the invasive margin of tumors could predict survival of early-stage colorectal cancer patients (J. Clin. Oncol. 2009;27:5944–51 and 2011;29:610–8). “This [immune profile] was an even stronger predictor of survival than TNM classification,” Galon said. Multiple studies of several other cancers, including breast, ovarian, and rectal cancer, found similar associations. Evidence that the immune system is an important ally in attacking cancer dates back 50 years, Fox said. But the methods used in existing studies have been wildly inconsistent.