tbuckley/cabot-search huggingface dataset:
Dietary antioxidants and the aetiology of pancreatic cancer: a cohort study using data from food diaries and biomarkers
Authors: Paul J R Banim, Robert Luben, Alison McTaggart, Ailsa Welch, Nicholas Wareham, Kay-Tee Khaw, Andrew R Hart
Journal: Gut (2012)

To investigate whether the dietary antioxidants vitamins C and E, selenium and zinc decrease the risk of developing pancreatic cancer, for the first time using 7-day food diaries, the most accurate dietary methodology in prospective work.23,658 participants, aged 40-74 years, recruited into the EPIC-Norfolk Study completed 7-day food diaries which recorded foods, brands and portion sizes. Nutrient intakes were calculated in those later diagnosed with pancreatic cancer and in 3970 controls, using a computer program with information on 11,000 foods. Vitamin C was measured in serum samples. The HRs of developing pancreatic cancer were estimated across quartiles of intake and thresholds of the lowest quartile (Q1) against a summation of the three highest (Q2-4).Within 10 years, 49 participants (55% men), developed pancreatic cancer. Those eating a combination of the highest three quartiles of all of vitamins C and E and selenium had a decreased risk (HR=0.33, 95% CI 0.13 to 0.84, p<0.05). There were threshold effects (Q2-4 vs Q1) for selenium (HR=0.49, 95% CI 0.26 to 0.93, p<0.05) and vitamin E (HR=0.57, 95% CI 0.29 to 1.09, p<0.10). The HRs of quartiles for antioxidants, apart from zinc, were <1, but not statistically significant. For vitamin C, there was an inverse association with serum measurements (HR trend=0.67, 95% CI 0.49 to 0.91, p=0.01), but the threshold effect from diaries was not significant (HR=0.68, 95% CI 0.37 to 1.26).The results support measuring antioxidants in studies investigating the aetiology of pancreatic cancer. If the association is causal, 1 in 12 cancers might be prevented by avoiding the lowest intakes.
Responsiveness of the WOMAC osteoarthritis index as compared with the SF-36 in patients with osteoarthritis of the legs undergoing a comprehensive rehabilitation intervention
Authors: F Angst, A Aeschlimann, W Steiner, G Stucki
Journal: Annals of the Rheumatic Diseases (2001)

To compare the responsiveness of the condition-specific Western Ontario and McMaster Universities osteoarthritis (OA) index (WOMAC) and the generic Short Form-36 (SF-36) in patients with OA of the legs undergoing a comprehensive inpatient rehabilitation intervention.A prospective follow up study of consecutively referred inpatients of a rehabilitation clinic was made. The patients included fulfilled the American College of Rheumatology criteria for knee or hip OA and underwent both passive and, particularly, active physical therapy for three to four weeks. Responsiveness assessment was performed using the standardised response mean (SRM), effect size, and Guyatt's responsiveness statistic between admission and discharge (end of rehabilitation) and then again between admission and three months later. For pain and function the SRMs were stratified by sex and OA joint. Effects were tested by the t test and SRMs of different scales were compared by the jack knife test.At the three month follow up, complete data were obtained for 223 patients. In general, the three responsiveness statistics showed a similar order of responsiveness. For both instruments, the pain scales were more responsive than the function scales. The responsiveness of the pain scale of both instruments was comparable (SRM=0.723 for WOMAC and SRM=0.528 for SF-36 at the end of rehabilitation; SRM=0.377 for WOMAC and SRM=0.468 for SF-36 at the three month follow up). In the measurement of function, the WOMAC was significantly more responsive than the SF-36 (SRMs, end of rehabilitation: 0.628 v 0.249; three month follow up: 0.235 v -0.001). Responsiveness tended to be higher in women and in knee OA than in men and hip OA.Both instruments, the WOMAC and the SF-36, capture improvement in pain in patients undergoing comprehensive inpatient rehabilitation intervention. Functional improvement can be detected better by the WOMAC than by the SF-36. All the other scales of both instruments were more weakly responsive.
Erlotinib Directly Inhibits HER2 Kinase Activation and Downstream Signaling Events in Intact Cells Lacking Epidermal Growth Factor Receptor Expression
Authors: Gabriele Schaefer, Lihua Shao, Klara Totpal, Robert W. Akita
Journal: Cancer Research (2007)

Erlotinib (Tarceva), is an orally available, reversible inhibitor of epidermal growth factor receptor (EGFR; HER1) that exhibits inhibitory activity on purified HER2 kinase at much higher concentrations. Despite the minimal activity on purified protein in vitro, in vivo studies show that erlotinib inhibits the growth of HER2-driven systems effectively. Several hypotheses have been put forward to explain this discrepancy. In particular, it has been suggested that erlotinib might indirectly suppress the activity of HER2 by blocking the ability of EGFR to transactivate it when the two receptors are part of a heterodimer complex. However, an alternative possibility that has not been adequately addressed is whether the direct inhibitory action of erlotinib on the HER2 kinase might account for the observed biological responses. To distinguish between a direct effect of erlotinib on HER2 kinase in intact cells or an indirect effect of erlotinib on HER2 activity that is mediated through EGFR, we generated cell lines that express either EGFR-H2 chimeric receptor or HER2 and HER3 receptors in an EGFR-negative background. We show that dose-dependent inhibition of HER2 was achieved at the receptor level, on downstream signaling molecules, and more importantly was also translated into inhibition of cell growth. Our findings imply that the inhibitory effect of erlotinib in HER2-expressing cells may in part be mediated through direct interaction with HER2 rather than indirectly through a process that requires the presence of EGFR.
STUDIES CONCERNING THE SITE OF RENIN FORMATION IN THE KIDNEY
Authors: A. Kaplan, Meyer Friedman
Journal: The Journal of Experimental Medicine (1942)

1. Renin was found in both the mesonephric and metanephric kidneys of the smallest hog fetuses examined. These were from 17 to 24 mm. in length in the case of the former, and 25 to 49 mm. in that of the latter. 2. No evidence was found in either type of kidney of juxtaglomerular cells described by Goormaghtigh as the probable site of renin formation. 3. The renin content in both the mesonephros and the metanephros was found to be independent of its arteriologlomerular component but directly dependent upon the number, size, and functional state of the tubular component. It increased in amount with increasing tubular proliferation during the course of embryonic development, and decreased with the progressive tubular atrophy and degeneration incident thereto. 4. The site of renin formation is discussed.
Angiotensin II modulates calponin mRNA expression in aortic smooth muscle cells in vitro and in vivo
Authors: W.M.M. van de Greef, G. Castoldi, C.R.T. di Gioia, F. Clementi, M.-R. Camellitti, P. Camisasea, F. Pionizzi, G. Panzacchi, G. Sperti, A. Stella
Journal: Journal of the American College of Cardiology (1998)
Human fat cell lipolysis is primarily regulated by inhibitory modulators acting through distinct mechanisms.
Authors: H Kather, W Bieger, G Michel, K Aktories, K H Jakobs
Journal: Journal of Clinical Investigation (1985)

The effects of adenosine deaminase and of pertussis toxin on hormonal regulation of lipolysis were investigated in isolated human fat cells. Adenosine deaminase (1.6 micrograms/ml) caused a two-to threefold increase in cyclic AMP, which was associated with an increase in glycerol release averaging 150-200% above basal levels. Clonidine, N6-phenylisopropyladenosine, prostaglandin E2, and insulin caused a dose-dependent inhibition of glycerol release in the presence of adenosine deaminase. Pretreatment of adipocytes with pertussis toxin (5 micrograms/ml) for 180 min resulted in a five- to sevenfold increase in cyclic AMP. Glycerol release was almost maximal and isoproterenol caused either no further increase or only a marginal additional increase of lipolysis after pretreatment with pertussis toxin, whereas cyclic AMP levels were 500 times higher than in controls. The effects of antilipolytic agents known to affect lipolysis by inhibition of adenylate cyclase activity, i.e., clonidine, N6-phenylisopropyladenosine, and prostaglandin E2, were impaired. In contrast, the antilipolytic action of insulin was preserved in adipocytes pretreated with pertussis toxin. As in controls, the peptide hormone had no detectable effect on cyclic AMP after pertussis toxin treatment. The findings support the view that the antilipolytic effect of insulin does not require adenylate cyclase or phosphodiesterase action. In addition, the results demonstrate that, upon relief of endogenous inhibition, human fat cell lipolysis proceeds at considerable (adenosine deaminase) or almost maximal (pertussis toxin) rates. A certain degree of inhibition, therefore, appears to be necessary for human fat cell lipolysis to be susceptible for hormonal activation.
Are sleep, nocturnal breathing and daytime performance impaired at moderate altitude?
Authors: Tsogyal D. Latshang, Christian M. Lo Cascio, Katrin Stadelmann, Noemi Tesler, Anne-Christin Stöwhas, Peter Achermann, Reto Huber, Malcolm Kohler, Konrad E. Bloch
Journal: European Respiratory Journal (2011)

Background:  There are concerns that even mild hypoxia at altitude has unfavorable health effects. The current study evaluates the hypothesis that sleep quality and daytime performance of lowlanders are impaired during a stay at moderate altitude.   Methods:  50 healthy men, mean±SD age 26±9 y, living at    Results:  Compared to 490m, sleep studies at altitude revealed reduced oxygen saturation, a higher central apnea/hypopnea index and reduced slow wave sleep. Multiple logistic regression did not show an independent effect of altitude on reaction times in PVT and snowboard simulator when controlled for various confounders.   Conclusion:  In healthy men, mild nocturnal hypoxemia and periodic breathing at moderate altitude are associated with subtle sleep disturbances but neither subjective sleep quality nor psychomotor vigilance during daytime are impaired.  Grants: Zurich Centre for Integrative Human Physiology, Swiss Federal Accident Insurance.
Randomized trial comparing weekly versus 3-week chemotherapy in small-cell lung cancer: a Cancer Research Campaign trial.
Authors: R L Souhami, R Rudd, M C Ruiz de Elvira, L James, N Gower, P G Harper, J S Tobias, M R Partridge, A G Davison, C Trask
Journal: Journal of Clinical Oncology (1994)

PURPOSE A randomized trial of chemotherapy, given on either a 1-week or a 3-week schedule, was performed in small-cell lung cancer (SCLC) patients. The aim was to determine if weekly scheduling produced survival superior to conventional treatment. PATIENTS AND METHODS Four hundred thirty-eight patients with SCLC with either limited disease (LD; 276 patients) or good-prognosis extensive disease (ED; 162 patients) were randomized. Weekly chemotherapy was 12 alternating cycles of ifosfamide/doxorubicin and cis-platin/etoposide (PE), while 3-week treatment was six alternating cycles of cyclophosphamide/doxorubicin/vincristine (CAV) and PE. Thoracic irradiation was administered 3 weeks after completion of chemotherapy to LD patients who attained a complete response (CR) or partial response (PR). Patients were well matched for clinical characteristics and prognostic factors. RESULTS Overall response was the same in both arms: 82.3% (39.4% CR) with weekly and 81.1% (36.9% CR) with 3-week treatment. The median survival (MS) durations were 10.8 and 10.6 months for weekly and 3-week chemotherapy, respectively. The 2-year survival rates were 11.8% and 11.7% in the weekly and 3-week arms, respectively. Received dose-intensity (DI) was 73.9% of projected for weekly treatment and 92.7% for 3-week treatment. Hematologic toxicity was the major dose-limiting toxicity for the weekly treatment. CONCLUSION This trial excludes at 90% power a benefit of greater than 10% for 2-year survival for weekly treatment. The received DI was reduced to a greater extent with weekly treatment, mainly due to hematologic toxicity.
Variants in the ATM gene and breast cancer susceptibility
Authors: Roger L Milne
Journal: Genome Medicine (2009)

It has been established that heterozygous carriers of ataxia-telangiectasia-causing mutations in the ATM gene are at approximately two-fold higher risk of breast cancer. Several studies have attempted to assess the potential implication of the gene's more common variants in breast cancer susceptibility. Three large case-control studies have consistently found no evidence of association for variants with minor allele frequency greater than 5%. Other studies have evaluated associations for coding variants with intermediate frequency (1-5%), but the results are inconsistent. Larger and/or combined association studies are needed to clarify this issue.
Evolutionary Dynamics of the SGM Transposon Family in the Drosophila obscura Species Group
Authors: Wolfgang J. Miller, Alexander Nagel, Jutta Bachmann, Lutz Bachmann
Journal: Molecular Biology and Evolution (2000)

SGM (Drosophila subobscura, Drosophila guanche, and Drosophila madeirensis) transposons are a family of transposable elements (TEs) in Drosophila with some functional and structural similarities to miniature inverted-repeat transposable elements (MITEs). These elements were recently active in D. subobscura and D. madeirensis (1–2 MYA), but in D. guanche (3–4 MYA), they gave rise to a species-specifically amplified satellite DNA making up approximately 10% of its genome. SGM elements were already active in the common ancestor of all three species, giving rise to the A-type specific promoter section of the P-related neogene cluster. SGM sequences are similar to elements found in other obscura group species, such as the ISY elements in D. miranda and the ISamb elements in Drosophila ambigua. SGM elements are composed of different sequence modules, and some of them, i.e., LS and LS-core, are found throughout the Drosophila and Sophophora radiation with similarity to more distantly related TEs. The LS-core module is highly enriched in the noncoding sections of the Drosophila melanogaster genome, suggesting potential regulatory host gene functions. The SGM elements can be considered as a model system elucidating the evolutionary dynamics of mobile elements in their arms race with host-directed silencing mechanisms and their evolutionary impact on the structure and composition of their respective host genomes.
Prediction models for rheumatoid arthritis during diagnostic investigation: evaluation of combinations of rheumatoid factor, anti-citrullinated protein/peptide antibodies and the human leucocyte antigen-shared epitope
Authors: B. Vander Cruyssen, I. E A Hoffman, I. Peene, A. Union, H. Mielants, L. Meheus, F. De Keyser
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objectives:</b> To calculate the probabilities for rheumatoid arthritis in a consecutive cohort of patients during diagnostic investigation. Different logistic regression models evaluating the value of human leucocyte antigen (HLA)-shared epitope determination and testing for rheumatoid factor and anti-citrullinated protein/peptide antibodies (ACPA) were fitted. <b>Methods:</b> 1003 consecutive patients were included in the study, presenting a new diagnostic problem for which rheumatoid arthritis was included in the differential diagnosis. All patients were tested for ACPA, rheumatoid factor and HLA-shared epitope. <b>Results:</b> After 1 year, diagnoses were established: 153 patients had definite rheumatoid arthritis and 629 patients had rheumatoid arthritis excluded. Rheumatoid factor, used as a continuous marker, is useful in evaluating the probability for rheumatoid arthritis. Combined rheumatoid factor and shared epitope testing may provide additional predictive information, but combined ACPA and rheumatoid factor testing is superior. The redundancy of shared epitope testing in a model that includes ACPA testing can be explained by the high association between ACPA and shared epitope both in patients with rheumatoid arthritis and in those with non-rheumatoid arthritis. The value of rheumatoid factor testing increased if patients presented with at least one swollen joint at baseline. <b>Conclusion:</b> Valid probabilities for rheumatoid arthritis during routine diagnostic investigation were calculated, and showed that the potential additional value of shared epitope testing disappears when ACPA testing is available. Combined rheumatoid factor and ACPA testing is useful, especially when rheumatoid factor is considered as a continuous parameter reflecting an increasing probability for rheumatoid arthritis at higher rheumatoid factor titres. The value of (continuous) rheumatoid factor testing increases when the a priori chance is higher.
Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial
Authors: James B Bussel, Drew Provan, Tahir Shamsi, Gregory Cheng, Bethan Psaila, Lidia Kovaleva, Abdulgabar Salama, Julian M Jenkins, Debasish Roychowdhury, Bhabita Mayer, Nicole Stone, Michael Arning
Journal: The Lancet (2009)
Confidentiality of medical records.
Authors: C P Brown
Journal: BMJ (1978)

volved.Some patients may have spent time in an intensive treatment unit or in a medical ward before transfer, but 75 % are discharged within 48 h of admission to the unit, approxi- mately 15 % to psychiatric hospitals.Outpatient follow-up is now carried out in the unit, which has reduced the default rate to less than 5 %, and over the past three years the relapse rate, defined as repeat of selfpoisoning within 12 months, has fallen to less than 10%.
Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992-2006
Authors: Ahmedin Jemal, Mona Saraiya, Pragna Patel, Sai S. Cherala, Jill Barnholtz-Sloan, Julian Kim, Charles L. Wiggins, Phyllis A. Wingo
Journal: Journal of the American Academy of Dermatology (2011)

Increasing cutaneous melanoma incidence rates in the United States have been attributed to heightened detection of thin (≤ 1-mm) lesions.We sought to describe melanoma incidence and mortality trends in the 12 cancer registries covered by the Surveillance, Epidemiology, and End Results program and to estimate the contribution of thin lesions to melanoma mortality.We used joinpoint analysis of Surveillance, Epidemiology, and End Results incidence and mortality data from 1992 to 2006.During 1992 through 2006, melanoma incidence rates among non-Hispanic whites increased for all ages and tumor thicknesses. Death rates increased for older (>65 years) but not younger persons. Between 1998 to 1999 and 2004 to 2005, melanoma death rates associated with thin lesions increased and accounted for about 30% of the total melanoma deaths.Availability of long-term incidence data for 14% of the US population was a limitation.The continued increases in melanoma death rates for older persons and for thin lesions suggest that the increases may partly reflect increased ultraviolet radiation exposure. The substantial contribution of thin lesions to melanoma mortality underscores the importance of standard wide excision techniques and the need for molecular characterization of the lesions for aggressive forms.
Tamoxifen Use in Postmenopausal Breast Cancer: CYP2D6 Matters
Authors: Hiltrud Brauch, Werner Schroth, Matthew P. Goetz, Thomas E. Mürdter, Stefan Winter, James N. Ingle, Matthias Schwab, Michel Eichelbaum
Journal: Journal of Clinical Oncology (2012)

The question of whether genetic polymorphisms of CYP2D6 can affect treatment outcome in patients with early postmenopausal breast cancer has been a matter of debate. With the recent negative results with regard to CYP2D6 genotyping from the Breast International Group (BIG) 1-98 and Arimidex, Tamoxifen, Alone or in Combination (ATAC) studies, the study investigators suggest that testing for CYP2D6 has no value in clinical practice.1,2 The authors of the accompanying editorial conclude that this matter can be likely laid to rest.3 However, pharmacogenetic experts demanded the retraction of the BIG 1-98 CYP2D6 study4 on the basis of massive departures from Hardy-Weinberg equilibrium (HWE; Table 1), possibly because of the bias that may result when the CYP2D6 genotype is obtained from the tumor (somatic) genome and not the host genome (germline DNA). Various authors in their letters attribute the highly distorted genotype frequencies to allelic imbalance associated with loss of heterozygosity (LOH) in breast tumor tissue,4,5 deviation from the standard genotyping assay protocol,5 or the presence of pseudogenes neighboring the CYP2D6 locus.6 Because the BIG 1-98 and ATAC pharmacogenetic studies may be considered sufficient to settle the issue of the value of CYP2D6 in decision making regarding endocrine therapy in postmenopausal women with breast cancer, we revisit the hypothesis, comment on the complementary evidence, and discuss pros and cons of the validity of CYP2D6 tamoxifen pharmacogenetics.
A British Medical Association Lecture on THE DIAGNOSIS AND TREATMENT OF PULMONARY TUBERCULOSIS
Authors: W. A. Dickson
Journal: BMJ (1930)

MEDICALJONAMole imllpossible, if this can be, for one human braini to assimilate the whole of these facts and put thtem to l)ractical use.The buirniing questioni eveni niow is, How manir of these facts is it desirable-should we say necessairy -foi a gee(rz.ilpractitioner to know?WImt I wish to further is the teachinig-of anatomy in sucli a mainnier that the finiite miind may obtain and retain those wliieli are essential.I consider that this requires a good deal of " heterodoxy " in time relatinig of anatomy to surgery.jUtItI5 4i rat Asoriation 3WIaturt ON
Eccentric hip adduction and abduction strength in elite soccer players and matched controls: a cross-sectional study
Authors: K Thorborg, C Couppé, J Petersen, S P Magnusson, P Hölmich
Journal: British Journal of Sports Medicine (2009)

Background Eccentric hip adduction and abduction strength plays an important role in the treatment and prevention of groin injuries in soccer players. Lower extremity strength deficits of less than 10% on the injured side, compared to the uninjured side, have been suggested as the clinical milestone before returning to sports following injury. Objective To examine whether a side-to-side eccentric hip adduction or abduction strength symmetry can be assumed in non-injured soccer players and matched controls. Material and Methods Nine elite soccer players 19.4 (1.5) years and nine recreational athletes 19.5 (2.0) years matched for sex, height and weight were included. Eccentric hip adduction and abduction strength of the dominant and non-dominant leg was tested for all the participants using an eccentric break test with a handheld dynamometer. Results The dominant leg was 14% stronger than the non-dominant leg for hip adduction in the soccer players (p&lt;0.05). No other side-to-side strength differences existed in soccer players or controls. In soccer players, hip abduction strength was 17–31% greater than controls for the dominant (p&lt;0.05) and non-dominant leg (p&lt;0.001). Conclusion Eccentric hip adduction strength was greater in the dominant leg than in the non-dominant leg in soccer players, but not in matched controls. Eccentric hip abduction strength was greater in soccer players than matched controls, but soccer does not seem to induce a similar eccentric strength adaptation in the hip adductors.