tbuckley/cabot-search huggingface dataset:
Radiation Exposure and Thyroid Cancer
Authors: F. Owen Hoffman, A. James Ruttenber, Sander Greenland, Raymond J. Carroll
Journal: JAMA (2006)

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Hyperglycemia, Insulin Resistance, Impaired Pancreatic β-Cell Function, and Risk of Pancreatic Cancer
Authors: Brian M. Wolpin, Ying Bao, Zhi Rong Qian, Chen Wu, Peter Kraft, Shuji Ogino, Meir J. Stampfer, Kaori Sato, Jing Ma, Julie E. Buring, Howard D. Sesso, I-Min Lee, John Michael Gaziano, Anne McTiernan, Lawrence S. Phillips, Barbara B. Cochrane, Michael N. Pollak, JoAnn E. Manson, Edward L. Giovannucci, Charles S. Fuchs
Journal: JNCI Journal of the National Cancer Institute (2013)

Obesity and diabetes mellitus are associated with an increased risk of pancreatic cancer. These associations may be secondary to consequences of peripheral insulin resistance, pancreatic β-cell dysfunction, or hyperglycemia itself. Hemoglobin A1c (HbA1c) is a measure of hyperglycemia, whereas plasma insulin and proinsulin are markers of peripheral insulin resistance, and the proinsulin to insulin ratio marks pancreatic β-cell dysfunction.This was a prospective, nested case-control study of 449 case patients and 982 control subjects with prediagnostic blood samples and no diabetes history from five prospective US cohorts followed through 2008. Two or three control subjects were matched to each case patient by year of birth, cohort, smoking, and fasting status. Pancreatic cancer risk was assessed by prediagnostic HbA1c, insulin, proinsulin, and proinsulin to insulin ratio with multivariable-adjusted logistic regression. All P values were two-sided.The highest vs lowest quintiles of HbA1c, insulin, and proinsulin were associated with with an increased risk for pancreatic cancer (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.17 to 2.72, P trend = .04 for HbA1c; OR = 1.57; 95% CI = 1.08 to 2.30; Ptrend = .002 for insulin; and OR = 2.22; 95% CI = 1.50 to 3.29; P trend < .001 for proinsulin). Proinsulin to insulin ratio was not associated with pancreatic cancer risk. Results were similar across studies (all P heterogeneity > .29). In cancers developing 10 or more years after blood collection, the associations with insulin and proinsulin became stronger (highest vs lowest quintile, OR = 2.77; 95% CI = 1.28 to 5.99 for insulin and OR = 3.60; 95% CI = 1.68 to 7.72 for proinsulin). In mutually adjusted models including HbA1c, insulin, and proinsulin, only proinsulin remained statistically significant ( highest vs lowest quintile, OR = 2.55; 95% CI = 1.54 to 4.21; Ptrend < .001).Among participants from five large prospective cohorts, circulating markers of peripheral insulin resistance, rather than hyperglycemia or pancreatic β-cell dysfunction, were independently associated with pancreatic cancer risk.
Phase I Study of KW-0761, a Defucosylated Humanized Anti-CCR4 Antibody, in Relapsed Patients With Adult T-Cell Leukemia-Lymphoma and Peripheral T-Cell Lymphoma
Authors: Kazuhito Yamamoto, Atae Utsunomiya, Kensei Tobinai, Kunihiro Tsukasaki, Naokuni Uike, Kimiharu Uozumi, Kazunari Yamaguchi, Yasuaki Yamada, Shuichi Hanada, Kazuo Tamura, Shigeo Nakamura, Hiroshi Inagaki, Koichi Ohshima, Hitoshi Kiyoi, Takashi Ishida, Kouji Matsushima, Shiro Akinaga, Michinori Ogura, Masao Tomonaga, Ryuzo Ueda
Journal: Journal of Clinical Oncology (2010)

KW-0761, a defucosylated humanized anti-CC chemokine receptor 4 (CCR4) antibody, exerts a strong antibody-dependent cellular cytotoxic effect. This phase I study assessed the safety, pharmacokinetics, recommended phase II dose and efficacy of KW-0761 in patients with relapsed CCR4-positive adult T-cell leukemia-lymphoma (ATL) or peripheral T-cell lymphoma (PTCL).Sixteen patients received KW-0761 once a week for 4 weeks by intravenous infusion. Doses were escalated, starting at 0.01, 0.1, 0.5, and finally 1.0 mg/kg by a 3 + 3 design.Fifteen patients completed the protocol treatment. Only one patient, at the 1.0 mg/kg dose, developed grade 3 dose-limiting toxicities, skin rash, and febrile neutropenia, and grade 4 neutropenia. Other treatment-related grade 3 to 4 toxicities were lymphopenia (n = 10), neutropenia (n = 3), leukopenia (n = 2), herpes zoster (n = 1), and acute infusion reaction/cytokine release syndrome (n = 1). Neither the frequency nor severity of toxicities increased with dose escalation. The maximum tolerated dose was not reached. Therefore, the recommended phase II dose was determined to be 1.0 mg/kg. No patients had detectable levels of anti-KW-0761 antibody. The plasma maximum and trough, and the area under the curve of 0 to 7 days of KW-0761, tended to increase dose and frequency dependently. Five patients (31%; 95% CI, 11% to 59%) achieved objective responses: two complete (0.1; 1.0 mg/kg) and three partial (0.01; 2 at 1.0 mg/kg) responses.KW-0761 was tolerated at all the dose levels tested, demonstrating potential efficacy against relapsed CCR4-positive ATL or PTCL. Subsequent phase II studies at the 1.0 mg/kg dose are thus warranted.
Randomized, Placebo-Controlled Comparison of Amitriptyline, Duloxetine, and Pregabalin in Patients With Chronic Diabetic Peripheral Neuropathic Pain
Authors: Julia Boyle, Malin E.V. Eriksson, Laura Gribble, Ravi Gouni, Sigurd Johnsen, David V. Coppini, David Kerr
Journal: Diabetes Care (2012)

OBJECTIVE Chronic diabetic peripheral neuropathic pain (DPNP) is difficult to treat, with treatment regimens often inadequate at controlling pain and limited by side effects and drug tolerance. Secondary parameters, such as quality of sleep and mood, may also be important for successful DPNP management. The objectives of this study were to compare the analgesic efficacy of pregabalin, amitriptyline, and duloxetine, and their effect on polysomnographic sleep, daytime functioning, and quality of life in patients with DPNP. RESEARCH DESIGN AND METHODS This was a double-blind, randomized, parallel group investigation of type 1 and 2 diabetic subjects with DPNP. Each treatment group had a single-blind, 8-day, placebo run-in followed by 14 days of lower-dose and 14 days of higher-dose medication. At the end of each dose titration period, subjective pain, sleep, and daytime functioning were assessed during a 2-day residential period. RESULTS All medications reduced pain when compared with placebo, but no one treatment was superior to any other. For sleep, pregabalin improved sleep continuity (P &amp;lt; 0.001), whereas duloxetine increased wake and reduced total sleep time (P &amp;lt; 0.01 and P &amp;lt; 0.001). Despite negative effects on sleep, duloxetine enhanced central nervous system arousal and performance on sensory motor tasks. There were no significant safety findings; however, there was a significantly higher number of adverse events in the pregabalin treatment group. CONCLUSIONS There was no significant difference in analgesic efficacy between amitriptyline, duloxetine, and pregabalin. However, there were significant differences in the secondary parameters, which may be of relevance when deciding the optimal treatment for DPNP.
Increased plasma brain natriuretic peptide level as a guide for silent myocardial ischemia in patients with non-obstructive hypertrophic cardiomyopathy
Authors: Tomoki Nakamura, Kenzo Sakamoto, Tetsuhiro Yamano, Masayuki Kikkawa, Kan Zen, Takato Hikosaka, Takao Kubota, Akihiro Azuma, Tsunehiko Nishimura
Journal: Journal of the American College of Cardiology (2002)
Medical Oncologists' Attitudes and Practice in Cancer Pain Management: A National Survey
Authors: Brenda Breuer, Stewart B. Fleishman, Ricardo A. Cruciani, Russell K. Portenoy
Journal: Journal of Clinical Oncology (2011)

To evaluate the attitudes, knowledge, and practices of US medical oncologists that are related to management of cancer pain.An anonymous survey was mailed to a geographically representative sample of medical oncologists randomly selected from the American Medical Association's Physician Master File.From a total of 2,000 oncologists, 354 responded to the original questionnaire and 256 responded to one of two subsequent shortened versions (overall response rate, 32%). Responders were demographically similar to all US medical oncologists. Using numeric rating scales of 0 to 10, oncologists rated their specialty highly for the ability to manage cancer pain (median, 7; interquartile range [IQR], 6 to 8) but rated their peers as more conservative prescribers than themselves (median, 3; IQR, 2 to 5). The quality of pain management training during medical school and residency was rated as 3 (IQR, 1 to 5) and 5 (IQR, 3 to 7), respectively. The most important barriers to pain management were poor assessment (median, 6; IQR, 4 to 7) and patient reluctance to take opioids (median, 6; IQR, 5 to 7) or report pain (median, 6; IQR, 4 to 7). Other barriers included physician reluctance to prescribe opioids (median, 5; IQR, 3 to 7) and perceived excessive regulation (median, 4; IQR, 2 to 7). In response to two vignettes describing challenging clinical scenarios, 60% and 87%, respectively, endorsed treatment decisions that would be considered unacceptable by pain specialists. Frequent referrals to pain or palliative care specialists were reported by only 14% and 16%, respectively.These data suggest that, for more than 20 years, a focus on cancer pain has not adequately addressed the perception of treatment barriers or limitations in pain-related knowledge and practice within the oncology community. Additional efforts are needed to achieve meaningful progress.
Quantitative versus qualitative analysis of peak expiratory flow in occupational asthma.
Authors: J Cote, S Kennedy, M Chan-Yeung
Journal: Thorax (1993)

BACKGROUND: Peak expiratory flow rates (PEF) are often used to confirm the diagnosis of occupational asthma. The records are usually analysed qualitatively, and this may lead to interobserver disagreement. In this study the diagnostic value of a qualitative assessment of change in PEF was compared with objective measures of change in PEF and the results of a specific inhalation challenge test with plicatic acid. METHODS: Twenty five patients with possible red cedar asthma recorded PEF six times a day for three weeks at work and for two weeks away from work and underwent a challenge test with plicatic acid at the end of the recording period. Patients were considered to have cedar asthma if the FEV1 after inhalation of plicatic acid was 15% or more below that on the control day. PEF was plotted against time and assessed qualitatively by three physicians. The graph was considered positive for cedar asthma if two of the three physicians agreed that PEF was lower at work than away from work. The 95% confidence interval for variation in PEF between periods at work and away from work was also obtained from 15 asthmatic patients without occupational asthma. Differences in PEF between periods at work and away from work were considered positive for occupational asthma in the patients exposed to cedar when they were outside the 95% confidence interval for variations in PEF in the 15 patients whose asthma was nonoccupational. RESULTS: Of the 25 men studied, 15 had a positive response to plicatic acid. The qualitative PEF analysis had a sensitivity of 87% and a specificity of 90% in confirming red cedar asthma as diagnosed by the specific challenge test. Among the objective methods tested, only the difference in mean PEF between the maximum PEF at weekends and the minimum PEF on working days had a sensitivity (93%) greater than that of the qualitative method and a similar specificity. CONCLUSIONS: The qualitative assessment of PEF is a good diagnostic test for cedar asthma. Only one objective method of PEF analysis proved to be slightly more sensitive than the qualitative method and similar in specificity.
Local effects of acute cellular injury on regional myocardial blood flow.
Authors: F R Cobb, R J Bache, F Rivas, J C Greenfield
Journal: Journal of Clinical Investigation (1976)

This study was designed to examine local effects of acute cellular injury on regional myocardial blood flow. Studies were carried out in awake dogs chronically prepared with indwelling catheters in the aorta and left atrium and an occluder on the left circumflex coronary artery. Regional myocardial blood flow was measured by using 7-10-mum radioisotope-labeled microspheres after reestablishing inflow to a region subjected to a 2-h complete coronary occlusion. Microspheres were injected 15 s, 15 min, 4 h, and 3 days after reperfusion to assess effects of cell injury at varying intervals after reperfusion. Effects of acute cellular injury on blood flow were assessed by determining the relationship between regional blood flow and the extent of subsequent cellular necrosis measured in multiple tissue samples, weight 1-2 g, from the entire ischemic zone. The extent of cellular necrosis was determined from histological sections of each tissue sample. Prolonged ischemia effected local tissue responses which altered perfusion as a function of the interval after reperfusion and the subsequent extent of myocardial necrosis. Although the net response in each region immediately after reperfusion was vasodilation, the hyperemia in regions which subsequently suffered cellular necrosis was attenuated in direct proportion to the extent of subsequent infarction. Blood flow to acutely injured regions remained equal to, or in excess of, flow to nonischemic regions 15 min after reperfusion, but at 4 h and 3 days after reperfusion, flow was significantly decreased in regions with greater than 50% infarction. Thus, these data indicate that prolonged ischemia initiates tissue responses which progressively reduce myocardial perfusion after reperfusion. These effects on tissue perfusion may result from normal responses to irreversible injury and (or) abnormal responses to reversible and thus, potentially alterable, ischemic injury.
Minimum effective dose of chenic acid for gallstone patients: reduction with bedtime administration and low cholesterol diet.
Authors: D P Maudgal, R M Kupfer, T C Northfield
Journal: Gut (1982)

The aim of this study was to determine whether bedtime administration and a low cholesterol diet reduce the minimum effective dose of chenodeoxycholic (chenic) acid, defined as the dose giving a mean cholesterol saturation index of 0.8. Dose response studies were carried out in 10 patients with radiolucent gallstones in a functioning gallbladder during three different treatment regimens. On each regimen, all patients received three different doses of chenodeoxycholic acid in random order for one month each. Bedtime chenic acid plus a low cholesterol diet gave the greatest reduction in saturation index. A significant dose/response relationship was found on each regimen. On the conventional regimen of mealtime chenic acid, the minimum effective dose was 14 mg/kg/day; on bedtime chenic acid it was 12.4 mg/kg/day; and on bedtime chenic acid plus low cholesterol diet it was further reduced to 8.4 mg/kg/day (p less than 0.01). There was a dose-related increase in bowel frequency, which was absent at 10.6 mg/kg/day and below. We conclude that administration of chenic acid at bedtime with a low cholesterol diet enables the minimum effective dose for gallstone dissolution to be approximately halved, thus preventing diarrhoea and reducing the cost of treatment.
Myocardial Oxygen Consumption in Acute Experimental Cardiac Depression
Authors: THOMAS P. GRAHAM, JOHN ROSS, JAMES W. COVELL, EDMUND H. SONNENBLICK, RICHARD L. CLANCY
Journal: Circulation Research (1967)

Myocardial oxygen consumption (MV · o 2 ) during drug-induced cardiac depression was measured in 8 anesthetized, open chest dogs in which myocardial wall tension was controlled. The right side of the heart was bypassed and myocardial contractility was reduced with procaine HCl, propranolol, or pronethalol. MV · o 2 consistently fell during cardiac depression (avg = 1.52 ml/min per 100 g left ventricle or - 11.6%). These reductions occurred despite small increases in developed tension. Changes in the tension-time index, contractile element work, and contractile element power did not correlate invariably with ΔMV · o 2 , while reductions in velocity of the contractile elements at isotension, maximum left ventricular dp/dt, and the extent of shortening of the contractile elements and circumferential fibers were associated in every experiment with the reductions in MV · o 2 . The finding that negative inotropic influences are associated with a reduction in myocardial energy utilization, when considered with earlier observations showing that positive inotropic influences induce an augmentation of MV · o 2 , provides evidence that the inotropic state and its mechanical correlates are coupled with myocardial energy utilization by a mechanism that is independent of tension development.
Phase III Trial of Vinflunine Plus Best Supportive Care Compared With Best Supportive Care Alone After a Platinum-Containing Regimen in Patients With Advanced Transitional Cell Carcinoma of the Urothelial Tract
Authors: Joaquim Bellmunt, Christine Théodore, Tomasz Demkov, Boris Komyakov, Lisa Sengelov, Gedske Daugaard, Armelle Caty, Joan Carles, Agnieszka Jagiello-Gruszfeld, Oleg Karyakin, François-Michel Delgado, Patrick Hurteloup, Eric Winquist, Nassim Morsli, Yacine Salhi, Stéphane Culine, Hans von der Maase
Journal: Journal of Clinical Oncology (2009)

Purpose Vinflunine (VFL) is a new microtubule inhibitor that has activity against transitional cell carcinoma of urothelial tract (TCCU). We conducted a randomized phase III study of VFL and best supportive care (BSC) versus BSC alone in the treatment of patients with advanced TCCU who had experienced progression after a first-line platinum-containing regimen. Patients and Methods The study was designed to compare overall survival (OS) between patients receiving VFL + BSC (performance status [PS] = 0: 320 mg/m 2 , every 3 weeks; PS = 0 with previous pelvic radiation and PS = 1: 280 mg/m 2 subsequently escalated to 320 mg/m 2 ) or BSC. Results Three hundred seventy patients were randomly assigned (VFL + BSC, n =253; BSC, n = 117). Both arms were well balanced except there were more patients with PS more than 1 (10% difference) in the BSC arm. Main grade 3 or 4 toxicities for VFL + BSC were neutropenia (50%), febrile neutropenia (6%), anemia (19%), fatigue (19%), and constipation (16%). In the intent-to-treat population, the objective of a median 2-month survival advantage (6.9 months for VFL + BSC v 4.6 months for BSC) was achieved (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12) but was not statistically significant (P = .287). Multivariate Cox analysis adjusting for prognostic factors showed statistically significant effect of VFL on OS (P = .036), reducing the death risk by 23% (HR = 0.77; 95% CI, 0.61 to 0.98). In the eligible population (n = 357), the median OS was significantly longer for VFL + BSC than BSC (6.9 v 4.3 months, respectively), with the difference being statistically significant (P = .040). Overall response rate, disease control, and progression-free survival were all statistically significant favoring VFL + BSC (P = .006, P = .002, and P = .001, respectively). Conclusion VFL demonstrates a survival advantage in second-line treatment for advanced TCCU. Consistency of results exists with significant and meaningful benefit over all efficacy parameters. Safety profile is acceptable, and therefore, VFL seems to be a reasonable option for TCCU progressing after first-line platinum-based therapy.
EFFECTS OF A PREVENTION PROGRAM FOR HAMSTRING STRAIN INJURY ON OPTIMUM LENGTH OF THE KNEE FLEXORS
Authors: E Martínez-Ruiz, J Mendiguchia, JA Rubio-Arias, PE Alcaraz, F Esparza-Ros
Journal: British Journal of Sports Medicine (2014)

Background The hamstring muscles are especially vulnerable during the late swing phase of sprinting, where the simultaneous actions of hip flexion and knee extension actively stretch the hamstrings to greater lengths. Objective To assess whether a functional strengthening program (i.e. eccentric, plyometric and acceleration exercises) increased optimum lengths of the knee flexors in soccer players. Design Longitudinal, unblinded randomized controlled study. Setting Amateur male soccer players from nine Spanish teams of the same competitive level. Participants 52 players were assigned to an exercise group (EG) or a control group (CG). Over the study, 8 athletes (6 from CG and 2 from EG) were dropped due to personal reasons, contracting by other clubs or injuries (non-hamstring strain injuries). After these exclusions, 25 players constituted the EG (22.7±4.8 years; 71.2±8.4 kg; 174.5±5.6 cm) and 19 the CG (21.8±2.5 years; 71.1±6.5 kg; 176.8±6.2 cm). Interventions Both groups performed their habitual soccer training throughout the study (with a similar physical load profile). Additionally, the EG performed a functional strengthening preventive program twice per week for seven weeks. Main outcome measurements The optimum angle of peak torque (and therefore optimum length) was calculated through of a 4th order polynomial curve. Previously, each subject performed 6 maximum concentric repetitions on an isokinetic dynamometer at angular velocity of 60°/s. Results After the seven-week period, the optimum length of the EG during knee flexion was significantly greater (i.e. the optimum angle of peak torque was smaller; 39.85±8.42 pre-test vs 35.26±7.50 pos-test). Similarly, the EG (35.26±7.50) showed a significantly great optimum length in the pos-test than the CG (40.89±8.71). Conclusions The prevention program proposed increases the optimum length of the knee flexors, promoting the development of strength at longer muscle lengths.