tbuckley/cabot-search huggingface dataset:
IMMUNOLOGICAL INDUCTION OF INCREASED VASCULAR PERMEABILITY
Authors: P. M. Henson, C. G. Cochrane
Journal: The Journal of Experimental Medicine (1969)

Two mechanisms have been described whereby rabbit platelets in vitro may be induced to release their contained histamine by the reaction of antigen and antibody. Both processes require the participation of the complement system. In the first, the adherence of platelets to particulate antigens such as zymosan or erythrocytes which have fixed complement through the third component was followed by histamine release. Plasma lacking C6 activity was fully active in this system. In the second mechanism, the reaction of soluble antigen with antibody in the presence of plasma also caused release of histamine from platelets and platelet clumping was observed. The release process, which appeared to follow the adherence of platelets to the immune complex, required the action of C6 and perhaps the later-acting components. No evidence could be obtained that a soluble factor was produced which caused the release. Instead, an inhibitor of the release process was detected after incubation of antigen, antibody, and plasma. Antibody preparations capable of giving complement-dependent PCA reactions in rabbits were also shown to induce the release of histamine from platelets in vitro.
Androgen Suppression Plus Radiation Versus Radiation Alone for Patients With Stage D<sub>1</sub>/Pathologic Node-Positive Adenocarcinoma of the Prostate: Updated Results Based on National Prospective Randomized Trial Radiation Therapy Oncology Group 85-31
Authors: Colleen A. Lawton, Kathryn Winter, David Grignon, Miljenko V. Pilepich
Journal: Journal of Clinical Oncology (2005)

Purpose To update the effect of immediate androgen suppression in conjunction with standard external-beam irradiation versus radiation alone on a group of histologically lymph node-positive patients with adenocarcinoma of the prostate. Materials and Methods A national prospective randomized trial (Radiation Therapy Oncology Group 85-31) of standard external-beam irradiation plus immediate androgen suppression versus external-beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate. One hundred seventy-three patients in this trial had histologically involved lymph nodes. Ninety-eight patients received radiation plus immediate androgen suppression (luteinizing hormone–releasing hormone [LHRH] agonist), whereas 75 patients received radiation alone with hormonal manipulation instituted at the time of relapse. Results With a median follow-up of 6.5 years for all patients and 9.5 years for living patients, estimated progression-free survival with prostate-specific antigen (PSA) level less than 1.5 ng/mL at 5 and 9 years was 54% and 10%, respectively, for patients who received immediate LHRH agonist versus 33% and 4% for patients who received radiation alone with hormonal manipulation instituted at time of relapse (P &lt; .0001). Multivariate analysis revealed radiation therapy and immediate hormonal manipulation as having a statistically significant impact on all end points analyzed: absolute survival, disease-specific failure, metastatic failure, and biochemical control with PSA less than 4 ng/mL and less than 1.5 ng/mL. Conclusion Pending the results of randomized trials, patients with adenocarcinoma of the prostate who have pathologically involved pelvic lymph nodes (pathologic node-positive or clinical stage D 1 ) should be considered for external-beam irradiation plus immediate hormonal manipulation rather than radiation alone with hormone manipulation at the time of relapse.
Influence of training changes on the stability of specialty choices of UK medical graduates: surveys of the graduates of 2002 and 2008
Authors: Elena Svirko, Trevor W Lambert, Michael J Goldacre
Journal: Journal of the Royal Society of Medicine (2015)

Objectives To explore the impact of Modernising Medical Careers (MMC) training on the stability of medical career choices in the UK. Setting UK Participants Graduates of 2002 and 2008 from all UK medical schools, 1 and 3 years postgraduation. Design Questionnaire surveys were conducted of 2002 and 2008 graduates from all UK medical schools 1 and 3 years post graduation. Main outcome measures Doctors gave their specialty choice(s) and rated the influence of each of 11 factors on their career choice. Results 2008 graduates were a little more likely than graduates of 2002 to retain their year 1 choice in year 3 (77.3% vs. 73.3%; p = 0.002). Among 2008 graduates, the percentage retaining their year 1 choice varied between 42% (clinical oncology) and 79% (general practice). Enthusiasm for a specialty, student experience and inclinations before medical school were associated with choice retention; consideration of domestic circumstances and hours/working conditions were associated with changes of choice. 2008 graduates were more likely than 2002s to be influenced by enthusiasm for a specialty, self-appraisal of their skills, working hours and their domestic circumstances; and less likely to be influenced by their experience of jobs, a particular teacher/department or eventual financial prospects. Conclusions Post-MMC, graduates were less likely to change their career choice and more likely to be motivated by personal factors and self-assessment of their suitability to a particular area of work.
Mitochondrial Neurogastrointestinal Encephalomyopathy Mimicking Anorexia Nervosa
Authors: BEREND FEDDERSEN, LARISSA DE LA FONTAINE, JÖRN OLIVER SASS, JURGEN LUTZ, ANGELA ABICHT, THOMAS KLOPSTOCK, ISHWAR CHANDER VERMA, EVA MEISENZAHL, OLIVER POGARELL
Journal: American Journal of Psychiatry (2009)
Impact of Adjuvant Radiation Therapy on Urinary Continence Recovery After Radical Prostatectomy
Authors: Nazareno Suardi, Andrea Gallina, Giuliana Lista, Giorgio Gandaglia, Firas Abdollah, Umberto Capitanio, Paolo Dell'Oglio, Alessandro Nini, Andrea Salonia, Francesco Montorsi, Alberto Briganti
Journal: European Urology (2013)
CpG methylation of the FHIT, FANCF, cyclin-D2, BRCA2 and RUNX3 genes in Granulosa cell tumors (GCTs) of ovarian origin.
Authors: Varinderpal S Dhillon, Mohd Shahid, Syed Husain
Journal: Molecular Cancer (2004)

Granulosa cell tumors (GCTs) are relatively rare and are subtypes of the sex-cord stromal neoplasms. Methylation induced silencing in the promoters of genes such as tumor suppressor genes, DNA repair genes and pro-apoptotic genes is recognised as a critical factor in cancer development.We examined the role of promoter hypermethylation, an epigenetic alteration that is associated with the silencing tumor suppressor genes in human cancer, by studying 5 gene promoters in 25 GCTs cases by methylation specific PCR and RT-PCR. In addition, the compatible tissues (normal tissues distant from lesion) from three non-astrocytoma patients were also included as the control.Frequencies of methylation in GCTs were 7/25 (28 % for FHIT), 6/25 (24% for FNACF), 3/25 (12% for Cyclin D2), 1/25 (4% for BRCA2) and 14/25 (56%) in RUNX3 genes. Correlation of promoter methylation with clinical characteristics and other genetic changes revealed that overall promoter methylation was higher in more advanced stage of the disease. Promoter methylation was associated with gene silencing in GCT cell lines. Treatment with methylation or histone deacetylation-inhibiting agents resulted in profound reactivation of gene expression.These results may have implications in better understanding the underlying epigenetic mechanisms in GCT development, provide prognostic indicators, and identify important gene targets for treatment.
Computed tomographic staging of anterior mediastinal neoplasms.
Authors: E A Rendina, F Venuta, L Ceroni, M Martelli, G Gualdi, M Caterino, C Ricci
Journal: Thorax (1988)

Sixty patients with anterior mediastinal neoplasms undergoing computed tomography before surgical exploration were entered in a prospective study to assess the value of computed tomography in the preoperative staging of anterior mediastinal tumours. Correct prediction of location, size, and tissue density was obtained in all 60 cases. Correct identification of the nature of the tumours was achieved by computed tomography in 37 of the 54 previously undiagnosed cases. Particular attention was given to the evaluation of the relation of the tumour to adjacent mediastinal structures, to predict the feasibility of radical surgical procedures. Overall sensitivity, specificity, and accuracy in identifying resectability were 46%, 85%, and 64%, with positive and negative predictive indices of 78% and 58%. Capsulated or highly invasive lesions were clearly distinguished, and the presence or absence of infiltration of mediastinal vessels, pericardium, and chest wall was correctly recognised in most cases. It is suggested that the evaluation of anterior mediastinal neoplasms should include computed tomography because of its accuracy in predicting size, location, and tissue density of the neoplasm. Computed tomography may suggest, often with good reliability, the histological type of the tumour and its relation to contiguous mediastinal structures, thus contributing to the choice of the appropriate surgical approach or route for biopsy.
Molecular Predictors of Progression-Free and Overall Survival in Patients With Newly Diagnosed Glioblastoma: A Prospective Translational Study of the German Glioma Network
Authors: Michael Weller, Jörg Felsberg, Christian Hartmann, Hilmar Berger, Joachim P. Steinbach, Johannes Schramm, Manfred Westphal, Gabriele Schackert, Matthias Simon, Jörg C. Tonn, Oliver Heese, Dietmar Krex, Guido Nikkhah, Torsten Pietsch, Otmar Wiestler, Guido Reifenberger, Andreas von Deimling, Markus Loeffler
Journal: Journal of Clinical Oncology (2009)

The prognostic value of genetic alterations characteristic of glioblastoma in patients treated according to present standards of care is unclear.Three hundred one patients with glioblastoma were prospectively recruited between October 2004 and December 2006 at the clinical centers of the German Glioma Network. Two hundred fifty-eight patients had radiotherapy, 199 patients had temozolomide, 189 had both, and seven had another chemotherapy as the initial treatment. The tumors were investigated for TP53 mutation, p53 immunoreactivity, epidermal growth factor receptor, cyclin-dependent kinase CDK 4 or murine double minute 2 amplification, CDKN2A homozygous deletion, allelic losses on chromosome arms 1p, 9p, 10q, and 19q, O(6)-methylguanine methyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutations.Median progression-free (PFS) and overall survival (OS) were 6.8 and 12.5 months. Multivariate analysis revealed younger age, higher performance score, MGMT promoter methylation, and temozolomide radiochemotherapy as independent factors associated with longer OS. MGMT promoter methylation was associated with longer PFS (relative risk [RR], 0.5; 95% CI, 0.38 to 0.68; P < .001) and OS (RR, 0.39; 95% CI, 0.28 to 0.54; P < .001) in patients receiving temozolomide. IDH1 mutations were associated with prolonged PFS (RR, 0.42; 95% CI, 0.19 to 0.91; P = .028) and a trend for prolonged OS (RR, 0.43; 95% CI, 0.15 to 1.19; P = .10). No other molecular factor was associated with outcome.Molecular changes associated with gliomagenesis do not predict response to therapy in glioblastoma patients managed according to current standards of care. MGMT promoter methylation and IDH1 mutational status allow for stratification into prognostically distinct subgroups.
Relationship between disease activity and infection in patients with spondyloarthropathies
Authors: A Martínez, C Pacheco-Tena, J Vázquez-Mellado, R Burgos-Vargas
Journal: Annals of the Rheumatic Diseases (2004)

To assess the relationship between disease activity and signs and symptoms of infection in Mexican patients with spondyloarthropathies (SpA).A cross sectional study of 95 non-selected patients with SpA (62 men; mean age 26.4 years), who were examined for signs and symptoms of infection and their association with disease activity. 52 had ankylosing spondylitis (AS), 32 undifferentiated SpA (uSpA), 6 chronic reactive arthritis (ReA), and 5 psoriatic arthritis (PsA). Categorical data were analysed by chi(2) or Fisher's tests.53 (56%) patients had infections: 41 (43%) upper respiratory tract (URT), 34 (36%) enteric, and 20 (21%) genitourinary infections. More infections occurred in HLA-B27 positive patients as a whole (39 v 5; p = 0.003) and in uSpA (12 v 2; p = 0.005). In AS and uSpA, infections occurred in approximately 50%. 30/39 (77%) patients with active disease (group A) and 23/56 (41%) (group B) (p = 0.001) had infection. There were more enteric infections in group A (47%; p<0.001) and more URT infections in group B (52%; p = NS). 22/30 (73%) patients attributed disease activity to infection.Enteric, and less commonly, URT infections in Mexican patients with SpA, particularly those who were HLA-B27 positive, seem to have a role in the active phase of AS and uSpA.
Mini-Wright peak flow meters are reliable after 5 years use. Dutch CNSLD Study Group
Authors: WR Douma, TW van der Mark, HT Folgering, E Kort, HA Kerstjens, GH Koeter, DS Postma
Journal: European Respiratory Journal (1997)

In studies with a long-term follow-up, peak expiratory flow (PEF) meters are often used to assess bronchial obstruction. The question arises whether data obtained with these frequently used meters are still reliable after several years of use, and whether the old meters should be renewed after a certain period. In the present study, we tested the reliability of PEF values measured with mini-Wright PEF meters that had been used frequently for 5 yrs. The values obtained with these meters were compared with values measured with identical but new meters, in 50 patients with obstructive airways disease. Though statistically significant, there was no clinically significant difference in mean PEF measured with the old and new meters in most patients (mean difference 10.2 L.min-1). However, on an individual basis, the differences between old and new meters could be large (upper and lower limits of agreement (mean +/- 2 SD) being 63.6 and -43.2 L.min-1, respectively). We conclude that mean peak expiratory flow values measured with frequently used mini-Wright peak expiratory flow meters are still reliable after 5 yrs. In long-term studies, renewal of peak expiratory flow meters should be restricted to cases of obvious malfunction.
Athletes attending a sports injury clinic--a review.
Authors: M. D. Devereaux, S. M. Lachmann
Journal: British Journal of Sports Medicine (1983)

In a prospective study over the two years 1981-1982, there were 1186 separate sporting injuries treated at a Sports Injury Clinic. Just over 75% of patients were aged between 16 and 25 years old, while 80% were male. Football, Rugby, Running, Squash and Rowing contributed over 70% of these injuries. The commonest injuries were to the lower limb and lumbar region. In 43% of knee injuries there was strain of the collateral ligaments, while another 26% had patello-femoral pain. Short distance running was associated with an increase in shin splints, tibial stress fractures and hamstring injuries. Long distance running was associated with an increase in ankle and foot injuries. Sports Injury Clinics can benefit the injured athlete and there appears to be a need for their development in major hospitals.
Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells.
Authors: Gerald Brandacher, Alexander Perathoner, Ruth Ladurner, Stefan Schneeberger, Peter Obrist, Christiana Winkler, Ernst R Werner, Gabriele Werner-Felmayer, Helmut G Weiss, Georg G√∂bel, Raimund Margreiter, Alfred K√∂nigsrainer, Dietmar Fuchs, Albert Amberger
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: The pathologic interactions between tumor and host immune cells within the tumor microenvironment create an immunosuppressive network that promotes tumor growth and protects the tumor from immune attack. In this study, we examined the contribution of the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) on this phenomenon. EXPERIMENTAL DESIGN: Expression of IDO was analyzed in colorectal cancer cell lines by reverse transcription-PCR and functional enzyme activity was assessed by high-pressure liquid chromatography. Semiquantitative immunohistochemistry was used to evaluate IDO expression in the tissue samples of 143 patients with colorectal carcinoma, and was then correlated with the number of tumor-infiltrating T cells and clinical variables. RESULTS: In vitro IDO expression and functional enzyme activity in colorectal cancer cells was found to be strictly dependent on IFN-gamma stimulation. Immunohistochemical scores revealed IDO-high expression in 56 of 143 (39.2%) tumor specimens, whereas 87 of 143 (60.8%) cases showed low IDO expression levels. IDO-high expression was associated with a significant reduction of CD3+ infiltrating T cells (46.02 +/- 7.25) as compared with tissue samples expressing low IDO (19.42 +/- 2.50; P = 0.0003). Furthermore, IDO-high immunoreactivity significantly correlated with the frequency of liver metastases (P = 0.003). Kaplan-Meier analysis showed the crossing of survival curves at 45 months. By multivariate Cox's analysis, IDO-high expression emerged as an independent prognostic variable (&amp;lt;45 months, P = 0.006; &amp;gt;45 months, P = 0.04). CONCLUSION: IDO-high expression by colorectal tumor cells enables certain cancer subsets to initially avoid immune attack and defeat the invasion of T cells via local tryptophan depletion and the production of proapoptotic tryptophan catabolites. Thus, IDO significantly contributes to disease progression and overall survival in patients with colorectal cancer.
NEWLY DISCOVERED REDOX COFACTORS: Possible Nutritional, Medical, and Pharmacological Relevance to Higher Animals
Authors: William S. McIntire
Journal: Annual Review of Nutrition (1998)

▪ Abstract Research spurred by the discovery of pyrroloquinoline quinone (PPQ) in 1979 led to the discovery of four additional oxidation-reduction (redox) cofactors, all of which result from transmogrification of amino acyl side chains in respective enzymes. These cofactors are (a) topa quinone in copper-containing amine oxidases, enzymes found in nearly all forms of life, including human; (b) lysyl topa quinone of the copper protein lysyl oxidase, an enzyme required for proper cross-linking of collagen and elastin; (c) tryptophan tryptophylquinone of alkylamine dehydrogenases from gram-negative soil bacteria; and (d) the copper-complexed cysteinyl-tyrosyl radical of fungal galactose oxidase. Originally, PQQ was thought to be a covalently bound cofactor in numerous enzymes from eukaryotes and prokaryotes. Today, PQQ is only found as a noncovalent cofactor in bacterial enzymes. The ubiquity of PQQ in the environment and its ready accessibility in the human diet has raised questions concerning its role as a vitamin, or an essential or helpful nutrient. The relevance to nutrition, medicine, and pharmacology of PQQ, topa quinone, lysyl topa quinone, tryptophan trytophylquinone, the galactose oxidase cofactor, and the enzymes harboring these cofactors are discussed in this review.
Surgical resection for small cell carcinoma of the lung: a retrospective study.
Authors: E F Smit, H J Groen, W Timens, W J de Boer, P E Postmus
Journal: Thorax (1994)

A retrospective review was undertaken of the survival of 21 patients with histologically proven small cell carcinoma of the lung resected between 1977 and 1991.Twenty one patients (20 men) of median age 60 (range 44-73) years underwent surgical resection. Patients were subjected to standard clinical staging procedures. Preoperative diagnosis was small cell carcinoma of the lung in 13, non-small cell lung cancer in one, and uncertain in seven patients. Clinical staging was stage I disease in 11 and stage II in 10 patients.Resection included pneumonectomy in 12 cases, lobectomy in eight, and one wedge resection. Resection was complete in 16 patients. Postoperative histopathological examination confirmed small cell carcinoma of the lung in 19 specimens and mixed small cell and non-small cell carcinoma of the lung in two. Pathological staging was stage I in 11, stage II in three, and stage III in seven patients. The final pathological diagnosis of the resected specimens (n = 18) was atypical carcinoid in one, pure small cell carcinoma of the lung in 15, and mixed small cell and non-small cell carcinoma of the lung in two patients. Fourteen patients also received chemotherapy and 10 received prophylactic cranial irradiation postoperatively. Excluding the patient with a final diagnosis of atypical carcinoid, the median survival (n = 20) was 29 months (range two to 133+). Median survival for patients with pathological stage I and II disease (n = 13) was 40 months (range nine to 133+) and for patients with pathological stage III disease (n = 7) 20 months (range two to 116+). The median disease free survival was 23 months. Eleven patients relapsed between two and 101 months. There was no advantage for those patients who received postoperative chemotherapy.Curative resection offers the best chance for long term survival in patients with small cell carcinoma of the lung with very limited stage disease.
Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep.
Authors: E Van Cauter, J D Blackman, D Roland, J P Spire, S Refetoff, K S Polonsky
Journal: Journal of Clinical Investigation (1991)

To define the roles of circadian rhythmicity (intrinsic effects of time of day independent of the sleep or wake condition) and sleep (intrinsic effects of the sleep condition, irrespective of the time of day) on the 24-h variation in glucose tolerance, eight normal men were studied during constant glucose infusion for a total of 53 h. The period of study included 8 h of nocturnal sleep, 28 h of continuous wakefulness, and 8 h of daytime sleep. Blood samples for the measurement of glucose, insulin, C-peptide, cortisol, and growth hormone were collected at 20-min intervals throughout the entire study. Insulin secretion rates were derived from C-peptide levels by deconvolution. Sleep was polygraphically monitored. During nocturnal sleep, levels of glucose and insulin secretion increased by 31 +/- 5% and 60 +/- 11%, respectively, and returned to baseline in the morning. During sleep deprivation, glucose levels and insulin secretion rose again to reach a maximum at a time corresponding to the beginning of the habitual sleep period. The magnitude of the rise above morning levels averaged 17 +/- 5% for glucose and 49 +/- 8% for calculated insulin secretion. Serum insulin levels did not parallel the circadian variation in insulin secretion, indicating the existence of an approximate 40% increase in insulin clearance during the night. Daytime sleep was associated with a 16 +/- 3% rise in glucose levels, a 55 +/- 7% rise in insulin secretion, and a 39 +/- 5% rise in serum insulin. The diurnal variation in insulin secretion was inversely related to the cortisol rhythm, with a significant correlation of the magnitudes of their morning to evening excursions. Sleep-associated rises in glucose correlated with the amount of concomitant growth hormone secreted. These studies demonstrate previously underappreciated effects of circadian rhythmicity and sleep on glucose levels, insulin secretion, and insulin clearance, and suggest that these effects could be partially mediated by cortisol and growth hormone.