tbuckley/cabot-search huggingface dataset:
Transdermal 17-β-Estradiol and Risk of Developing Type 2 Diabetes in a Population of Healthy, Nonobese Postmenopausal Women
Authors: Rosario Rossi, Giorgia Origliani, Maria G. Modena
Journal: Diabetes Care (2004)

Various observational and randomized studies have demonstrated a reduction in the incidence of type 2 diabetes in postmenopausal women who received estrogen orally. No studies have been performed on the incidence of type 2 diabetes in postmenopausal women treated with transdermal 17-beta-estradiol. The purpose of our study was to assess the influence of transdermal 17-beta-estradiol on the incidence of type 2 diabetes in a population of healthy, nonobese postmenopausal women.Between January 1998 and December 2002, 673 healthy, nonobese postmenopausal women (mean age 54 +/- 5 years) were enrolled: 144 (21.4%) of these took transdermal 17-beta-estradiol and 529 (78.6%) had never taken hormones during their postmenopausal period. Final elaboration of the data took place in July 2003, with a mean follow-up of 3.7 +/- 0.7 years (ranging from 0.5 to 5 years).Type 2 diabetes developed in 60 patients during the follow-up period, which is the equivalent of 22 cases per 1,000 women-years. In the "hormones nonusers" group, diabetes developed in 10% (54 of 529 women; equivalent of 26.5 cases/1,000 women-years), whereas in the "hormones users" group, diabetes developed in 4.16% (6 of 144 women; equivalent of 12.1 cases/1,000 women-years). Transdermal 17-beta-estradiol emerged as a treatment that significantly reduced the risk of developing diabetes (RR 2.19, 95% CI 1.79-3.56; P=0.006).Our results suggest a significant reduction in the incidence of type 2 diabetes in our population of nonobese, healthy postmenopausal women who used transdermal 17-beta-estradiol. This could suggest that, in some women, the estrogen deficiency that occurs after menopause could represent a fundamental step in the process of diabetogenesis.
A placebo controlled, crossover study of azathioprine in Reiter's syndrome.
Authors: A Calin
Journal: Annals of the Rheumatic Diseases (1986)

Eight patients with intractable Reiter's disease were entered into a double blind, placebo controlled, crossover study of azathioprine versus placebo--each patient serving as his own control. Drug therapy was administered for 16 weeks, patients receiving azathioprine (eight weeks) or placebo (eight weeks) in random order. Azathioprine was given as 1 mg/kg body weight for the first month and 2 mg/kg body weight for the second month. Six individuals completed both arms of the crossover. One withdrew because of nausea during the first week (azathioprine), and a second subject withdrew at four weeks because of lack of efficacy (placebo). At the end of the 16 weeks five out of six preferred azathioprine and one placebo. The mean unweighted joint score decreased from 19.8 to 2.7 during the azathioprine medication but increased from 13.4 to 19.9 during the placebo period. Patients were unable to reduce their analgesic or non-steroidal anti-inflammatory drug requirements during the placebo period, but four out of six were able to do so during azathioprine therapy. There were no drug related laboratory abnormalities. The data suggest that azathioprine may work rapidly in Reiter's disease. If these essentially anecdotal findings of efficacy are confirmed, long term toxicity may not be an over-riding factor since for some patients therapy can be rapidly tapered at eight weeks--either because of adequate improvement or failure to respond.
Infection with Human Immunodeficiency Virus Type 1 (HIV-1) among Recipients of Antibody-Positive Blood Donations
Authors: Elizabeth Donegan
Journal: Annals of Internal Medicine (1990)

To assess the incidence of human immunodeficiency virus type 1(HIV-1) transmission by antibody (anti-HIV-1)-positive blood components, and to determine the immunologic and clinical course in HIV-1-infected recipients.We retrospectively tested approximately 200,000 donor blood component specimens stored in late 1984 and 1985 for anti-HIV-1, and we contacted recipients of positive specimens to determine their serologic status. They were compared with both recipients of HIV-1-negative transfusions and healthy (untransfused) controls. Subjects were seen at 3- to 6-month intervals for up to 4 years for clinical and immunologic evaluations.Of 133 recipients, 9 had other possible exposures. Excluding these cases, 111 of 124 (89.5%) were anti-HIV-1-positive (95% CI, 84.1% to 94.5%). The recipient's sex, age, underlying condition, and type of component did not influence infection rates. The cumulative risk for developing the acquired immunodeficiency syndrome (AIDS) within 38 months after transfusion was 13% (CI, 7.5% to 21.6%). At 36 +/- 3 months after the index transfusion, seropositive recipients had lower counts of CD2+CDw26+, CD4+, CD4+CD29+, and CD4+CD45RA+subsets and more CD8+I2+ lymphocytes than did recipients of anti-HIV-1-negative transfusions. The CD4+ and CD2+CDw26+subsets changed the most rapidly. The absolute CD8+ count remained normal.Transfusion of anti-HIV-1-positive blood infected 90% of recipients. The rate of progression to AIDS within the first 38 months after infection was similar to that reported for homosexual men and hemophiliacs. Although most lymphocyte subset counts changed over time, CD8+ counts were constant.
Phase I Clinical Trial of STA-4783 in Combination with Paclitaxel in Patients with Refractory Solid Tumors
Authors: Anna Berkenblit, Joseph P. Eder, David P. Ryan, Michael V. Seiden, Noriaki Tatsuta, Matthew L. Sherman, Thomas A. Dahl, Bruce J. Dezube, Jeffrey G. Supko
Journal: Clinical Cancer Research (2007)

Abstract Purpose: STA-4783 is a new compound that markedly enhances the therapeutic index of paclitaxel against human tumor xenograft models. A phase I clinical trial was undertaken to determine the maximum tolerated dose, toxicity profile, and pharmacokinetics of STA-4783 in combination with paclitaxel. Experimental Design: Adults with refractory solid tumors concurrently received STA-4783 and paclitaxel as a 3-h i.v. infusion at starting doses of 44 and 135 mg/m2, respectively. After increasing paclitaxel to 175 mg/m2, the STA-4783 dose was escalated as permitted by dose-limiting toxicity during the first 21-day cycle. Results: Thirty-five patients were treated with eight dose levels of STA-4783/paclitaxel. In patients receiving 175 mg/m2 paclitaxel, the incidence of severe toxicity increased with escalation of the STA-4783 dose above 263 mg/m2, and 438 mg/m2 was the maximum tolerated dose. All toxicities were typical of paclitaxel, with neutropenia, mucositis, and myalgia/arthralgia being dose limiting. Partial responses were achieved in one patient with Kaposi's sarcoma and another with ovarian cancer that progressed during prior treatment with paclitaxel. STA-4783 exhibited linear pharmacokinetics characterized by rapid elimination from plasma (biological half-life, 1.06 ± 0.24 h) and a low steady-state apparent volume of distribution (25.1 ± 8.1 L/m2). The total body clearance of paclitaxel decreased significantly with escalation of the STA-4783 dose. Conclusions: The STA-4783/paclitaxel combination was well tolerated with a toxicity profile similar to single-agent paclitaxel. Enhanced systemic exposure to paclitaxel resulting from a dose-dependent interaction with STA-4783 was associated with increased toxicity. Objective responses in two heavily pretreated patients, both with taxane exposure, have encouraged further clinical evaluation of this regimen.
Angiotensin I–converting enzyme and plasminogen activator inhibitor-1 gene variants: risk of mortality and fatal cardiovascular disease in an elderly population-based cohort
Authors: Bastiaan T Heijmans, Rudi G.J Westendorp, Dick L Knook, Cornelis Kluft, P.Eline Slagboom
Journal: Journal of the American College of Cardiology (1999)
Stroke in the Diabetic Patient
Authors: David S H Beul
Journal: Diabetes Care (1994)

A higher prevalence of stroke is found in the patient with both diagnosed and undiagnosed diabetes and glucose intolerance. Because of local cerebral acidosis caused by ischemia and hyperglycemia, morbidity and mortality from a stroke are increased. Most studies show that individuals with admission serum glucose > 120 mg/dl (6.7 mM) have a higher morbidity and mortality from a stroke. The prevalence of cerebral infarcts, especially lacunar infarcts, is increased and the prevalence of subarachnoid hemorrhage, cerebral hemorrhage, and transient ischemic attacks are decreased in the diabetic patient. Age, race, hypertension, and the presence of diabetic nephropathy and coronary and peripheral vascular disease are risk factors for stroke in the diabetic patient, whereas obesity, smoking, hyperlipidemia, and glycemic control are not. Investigation and treatment of the diabetic patient with a stroke is discussed.
Optimal Colorectal Cancer Staging Criteria in TNM Classification
Authors: Hideki Ueno, Hidetaka Mochizuki, Yoshito Akagi, Takaya Kusumi, Kazutaka Yamada, Masahiro Ikegami, Hiroshi Kawachi, Shingo Kameoka, Yasuo Ohkura, Tadahiko Masaki, Ryoji Kushima, Keiichi Takahashi, Yoichi Ajioka, Kazuo Hase, Atsushi Ochiai, Ryo Wada, Keiichi Iwaya, Hideyuki Shimazaki, Takahiro Nakamura, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2012)

Histologic components of the TNM classification system have been repeatedly revised since the fifth edition (TNM5). TNM classification revisions provide different criteria for categorizing tumor nodules without residual lymph node structure (ND). However, there are few systematic evaluations regarding the effectiveness of these revisions.A multicenter pathologic review for ND in colorectal cancer (CRC) was performed. Tumor staging defined by TNM5, sixth edition (TNM6), and seventh edition (TNM7) were compared on the basis of Akaike information criterion (AIC) and Harrell's concordance index (c-index). Moreover, TNM7's prognostic value was compared between the original ND and modified criteria, which considered all regional NDs as lymph node metastasis (LNM) irrespective of the original structure.In 1,716 treated patients with CRC (1994 to 1998), tumor stages (I/II/III) exhibited better prognoses in TNM7 (AIC, 3055.1; c-index, 0.7215) than in TNM6 (AIC, 3063.7; c-index, 0.7149), but not better than in TNM5 (AIC, 3051.6; c-index, 0.7240). Comparing the original TNM7 and modified criteria, 4.2% of patients were classified in different N stages (N0/N1/N2a/N2b); both AIC and the c-index were superior in the modified criteria (AIC, 3029.40; c-index, 0.7271) compared with the original criteria (AIC, 3040.58; c-index, 0.7230). Modified criteria were also associated with improved prognostic power of tumor stages (I/IIA/IIB/IIC/IIIA/IIIB/IIIC). These results were similar in another cohort of 2,242 treated patients with CRC (1999 to 2003).The prognostic value of TNM7 is better than that of TNM6; however, improvement over TNM5 is insignificant. By considering all regional NDs as LNM irrespective of their morphology, TNM classification can be simplified and its prognostic value improved.
Control of rice grain-filling and yield by a gene with a potential signature of domestication
Authors: Ertao Wang, Jianjun Wang, Xudong Zhu, Wei Hao, Linyou Wang, Qun Li, Lixia Zhang, Wei He, Baorong Lu, Hongxuan Lin, Hong Ma, Guiquan Zhang, Zuhua He
Journal: Nature Genetics (2008)
Effect of Communications Training on Medical Student Performance
Authors: Michael J. Yedidia
Journal: JAMA (2003)

Although physicians' communication skills have been found to be related to clinical outcomes and patient satisfaction, teaching of communication skills has not been fully integrated into many medical school curricula or adequately evaluated with large-scale controlled trials.To determine whether communications training for medical students improves specific competencies known to affect outcomes of care.A communications curriculum instituted in 2000-2001 at 3 US medical schools was evaluated with objective structured clinical examinations (OSCEs). The same OSCEs were administered to a comparison cohort of students in the year before the intervention.One hundred thirty-eight randomly selected medical students (38% of eligible students) in the comparison cohort, tested at the beginning and end of their third year (1999-2000), and 155 students in the intervention cohort (42% of eligible students), tested at the beginning and end of their third year (2000-2001).Comprehensive communications curricula were developed at each school using an established educational model for teaching and practicing core communication skills and engaging students in self-reflection on their performance. Communications teaching was integrated with clinical material during the third year, required clerkships, and was supported by formal faculty development.Standardized patients assessed student performance in OSCEs on 21 skills related to 5 key patient care tasks: relationship development and maintenance, patient assessment, education and counseling, negotiation and shared decision making, and organization and time management. Scores were calculated as percentage of maximum possible performance.Adjusting for baseline differences, students exposed to the intervention significantly outperformed those in the comparison cohort on the overall OSCE (65.4% vs 60.4%; 5.1% difference; 95% confidence interval [CI], 3.9%-6.3%; P<.001), relationship development and maintenance (5.3% difference; 95% CI, 3.8%-6.7%; P<.001), organization and time management (1.8% difference; 95% CI, 1.0%-2.7%; P<.001), and subsets of cases addressing patient assessment (6.7% difference; 95% CI, 5.9%-7.8%; P<.001) and negotiation and shared decision making (5.7% difference; 95% CI, 4.5%-6.9%; P<.001). Similar effects were found at each of the 3 schools, though they differed in magnitude.Communications curricula using an established educational model significantly improved third-year students' overall communications competence as well as their skills in relationship building, organization and time management, patient assessment, and negotiation and shared decision making-tasks that are important to positive patient outcomes. Improvements were observed at each of the 3 schools despite adaptation of the intervention to the local curriculum and culture.
Breathing exercises for asthma: a randomised controlled trial
Authors: M Thomas, R K McKinley, S Mellor, G Watkin, E Holloway, J Scullion, D E Shaw, A Wardlaw, D Price, I Pavord
Journal: Thorax (2008)

<h3>Background:</h3> The effect of breathing modification techniques on asthma symptoms and objective disease control is uncertain<b>.</b> <h3>Methods:</h3> A prospective, parallel group, single-blind, randomised controlled trial comparing breathing training with asthma education (to control for non-specific effects of clinician attention) was performed. Subjects with asthma with impaired health status managed in primary care were randomised to receive three sessions of either physiotherapist-supervised breathing training (n = 94) or asthma nurse-delivered asthma education (n = 89). The main outcome was Asthma Quality of Life Questionnaire (AQLQ) score, with secondary outcomes including spirometry, bronchial hyper-responsiveness, exhaled nitric oxide, induced sputum eosinophil count and Asthma Control Questionnaire (ACQ), Hospital Anxiety and Depression (HAD) and hyperventilation (Nijmegen) questionnaire scores. <h3>Results:</h3> One month after the intervention there were similar improvements in AQLQ scores from baseline in both groups but at 6 months there was a significant between-group difference favouring breathing training (0.38 units, 95% CI 0.08 to 0.68). At the 6-month assessment there were significant between-group differences favouring breathing training in HAD anxiety (1.1, 95% CI 0.2 to 1.9), HAD depression (0.8, 95% CI 0.1 to 1.4) and Nijmegen (3.2, 95% CI 1.0 to 5.4) scores, with trends to improved ACQ (0.2, 95% CI 0.0 to 0.4). No significant between-group differences were seen at 1 month. Breathing training was not associated with significant changes in airways physiology, inflammation or hyper-responsiveness. <h3>Conclusion:</h3> Breathing training resulted in improvements in asthma-specific health status and other patient-centred measures but not in asthma pathophysiology. Such exercises may help patients whose quality of life is impaired by asthma, but they are unlikely to reduce the need for anti-inflammatory medication.
CELLULAR SPECIFICITY IN THE HOMOGRAFT REACTION
Authors: Robert A. Prendergast
Journal: The Journal of Experimental Medicine (1964)

The present study offers direct evidence that cells from the regional lymph node draining first-set skin homografts in rabbits participate in the lymphoid infiltrate at distant sites of graft rejection. With the use of a newly devised method of injection, adequate amounts of tritiated thymidine could be confined to the reactive regional node, other dividing cells of the host remaining unlabeled. It was thus possible to detect the appearance of this uniquely labeled population of cells at remote test sites on the same animal, obviating the necessity for cell transfer. Under these conditions differential counts of the lymphoid elements failed to show a preponderance of labeled cells in the infiltrate accompanying homologous, compared with unrelated control, graft rejection. These results, together with other recently reported data, suggest that the specificity of the homograft reaction is probably dictated by some humoral factor that acts in concert with recently proliferated lymphoid cells to accomplish graft rejection.
Cardioprotection in the aging, diabetic heart: the loss of protective Akt signalling
Authors: Hannah J. Whittington, Idris Harding, Clemency I.M. Stephenson, Robert Bell, Derek J. Hausenloy, Mihaela M. Mocanu, Derek M. Yellon
Journal: Cardiovascular Research (2013)

AimsOld age and diabetes are risk factors that often coexist increasing the vulnerability of the heart to the lethal effects of ischaemia–reperfusion injury (IRI). However, to our knowledge, no investigations have examined IRI and cardioprotective signalling in animal models bearing these co-morbidities concomitantly. The ability of the heart to recover following IRI is greatly dependent on its innate cardioprotective potential, in which a central role is played by Akt. We aimed to investigate in an aging diabetic rat model, the susceptibility of the heart to IRI, the achievability of ischaemic preconditioning (IPC) against this lethal event, and the changes in Akt signalling, as the main prosurvival intracellular pathway.
T-cell therapy for EBV-associated nasopharyngeal carcinoma: preparative lymphodepleting chemotherapy does not improve clinical results
Authors: S. Secondino, M. Zecca, L. Licitra, A. Gurrado, I. Schiavetto, P. Bossi, L. Locati, R. Schiavo, S. Basso, F. Baldanti, R. Maccario, F. Locatelli, S. Siena, P. Pedrazzoli, P. Comoli
Journal: Annals of Oncology (2011)
MYOCARDIAL INFARCTION SYMPTOM PRESENTATION AND HOSPITAL MORTALITY: RELATIONSHIP TO AGE AND SEX IN THE NATIONAL REGISTRY OF MYOCARDIAL INFARCTION (NRMI)
Authors: John G. Canto, William J. Rogers, Robert J. Goldberg, Eric D. Peterson, Nanette K. Wenger, Viola Vaccarino, Catarina I. Kiefe, Paul Frederick, George Sopko, Z.J. Zheng
Journal: Journal of the American College of Cardiology (2010)
Desloratadine reduces systemic allergic inflammation following nasal provocation in allergic rhinitis and asthma patients
Authors: S. M. Reinartz, S. E. Overbeek, A. KleinJan, C. M. van Drunen, G.‐J. Braunstahl, H. C. Hoogsteden, W. J. Fokkens
Journal: Allergy (2005)

Preclinical studies have demonstrated that some second-generation antihistamines have anti-inflammatory effects. It is not known whether these effects are also demonstrable in vivo. In this study we investigated the effect of treatment with desloratadine (DL) on systemic inflammation and on nasal and bronchial mucosal inflammation after nasal allergen provocation (NP) in subjects with grass-pollen-allergic rhinitis and asthma.Twenty-six subjects with grass-pollen-allergic rhinitis and asthma were randomly allocated to 8 days of treatment with DL (n = 13) or placebo (n = 13) outside the grass pollen season. On day 7 they underwent nasal provocation with grass pollen allergen. Nasal and bronchial biopsies were taken for immunohistochemical evaluation, and blood samples were analysed. Rhinitis and asthma symptoms, peak nasal inspiratory flow and peak expiratory flow, were also measured at specified times.The number of circulating eosinophils decreased during DL treatment, and there was a reduced increase in circulating eosinophils after NP in these subjects. There was also a significant reduction in early bronchial clinical response. There was no significant lessening in the severity of the nasal symptoms. Nasal and bronchial mucosal inflammation parameters did not alter under DL treatment.These data suggest that treatment with DL reduces systemic eosinophilia and prevents the increase in circulating eosinophils after NP. DL also significantly reduces the early bronchial clinical response to NP. However, airway mucosal inflammation is not altered by 1 week of treatment.
Molecular Features of the Transition from Prostatic Intraepithelial Neoplasia (PIN) to Prostate Cancer
Authors: Shingo Ashida, Hidewaki Nakagawa, Toyomasa Katagiri, Mutsuo Furihata, Megumi Iiizumi, Yoshio Anazawa, Tatsuhiko Tsunoda, Ryo Takata, Kotaro Kasahara, Tsuneharu Miki, Tomoaki Fujioka, Taro Shuin, Yusuke Nakamura
Journal: Cancer Research (2004)

Abstract To characterize the molecular feature in prostate carcinogenesis and the putative transition from prostatic intraepithelial neoplasia (PIN) to invasive prostate cancer (PC), we analyzed gene-expression profiles of 20 PCs and 10 high-grade PINs with a cDNA microarray representing 23,040 genes. Considering the histological heterogeneity of PCs and the minimal nature of PIN lesions, we applied laser microbeam microdissection to purify populations of PC and PIN cells, and then compared their expression profiles with those of corresponding normal prostatic epithelium also purified by laser microbeam microdissection. A hierarchical clustering analysis separated the PC group from the PIN group, except for three tumors that were morphologically defined as one very-high-grade PIN and two low-grade PCs, suggesting that PINs and PCs share some molecular features and supporting the hypothesis of PIN-to-PC transition. On the basis of this hypothesis, we identified 21 up-regulated genes and 63 down-regulated genes commonly in PINs and PCs compared with normal epithelium, which were considered to be involved in the presumably early stage of prostatic carcinogenesis. They included AMACR, OR51E2, RODH, and SMS. Furthermore, we identified 41 up-regulated genes and 98 down-regulated genes in the transition from PINs to PCs; those altered genes, such as POV1, CDKN2C, EPHA4, APOD, FASN, ITGB2, LAMB2, PLAU, and TIMP1, included elements that are likely to be involved in cell adhesion or the motility of invasive PC cells. The down-regulation of EPHA4 by small interfering RNA in PC cells lead to attenuation of PC cell viability. These data provide clues to the molecular mechanisms underlying prostatic carcinogenesis, and suggest candidate genes the products of which might serve as molecular targets for the prevention and treatment of PC.