tbuckley/cabot-search huggingface dataset:
Trajectories of Entering the Metabolic Syndrome
Authors: Oscar H. Franco, Joseph M. Massaro, Jacky Civil, Mark R. Cobain, Brendan O'Malley, Ralph B. D'Agostino
Journal: Circulation (2009)

Background— We evaluated the progression of the metabolic syndrome (MetS) and its components, the trajectories followed by individuals entering MetS, and the manner in which different trajectories predict cardiovascular disease and mortality. Methods and Results— Using data from 3078 participants from the Framingham Offspring Study (a cohort study) who attended examinations 4 (1987), 5 (1991), and 6 (1995), we evaluated the progression of MetS and its components. MetS was defined according to the Adult Treatment Panel III criteria. Using logistic regression, we evaluated the predictive ability of the presence of each component of the MetS on the subsequent development of MetS. Additionally, we examined the probability of developing cardiovascular disease or mortality (until 2007) by having specific combinations of 3 that diagnose MetS. The prevalence of MetS almost doubled in 10 years of follow-up. Hyperglycemia and central obesity experienced the highest increase. High blood pressure was most frequently present when a diagnosis of MetS occurred (77.3%), and the presence of central obesity conferred the highest risk of developing MetS (odds ratio, 4.75; 95% confidence interval, 3.78 to 5.98). Participants who entered the MetS having a combination of central obesity, high blood pressure, and hyperglycemia had a 2.36-fold (hazard ratio, 2.36; 95% confidence interval, 1.54 to 3.61) increase of incident cardiovascular events and a 3-fold (hazard ratio, 3.09, 95% confidence interval, 1.93 to 4.94) increased risk of mortality. Conclusions— Particular trajectories and combinations of factors on entering the MetS confer higher risks of incident cardiovascular disease and mortality in the general population and among those with MetS. Intense efforts are required to identify populations with these particular combinations and to provide them with adequate treatment at early stages of disease.
No Improvement of Posttraumatic Stress Disorder Symptoms With Guanfacine Treatment
Authors: Thomas Neylan
Journal: American Journal of Psychiatry (2006)

Objective: The authors report an 8-week, double-blind, randomized controlled trial of guanfacine versus placebo for posttraumatic stress disorder (PTSD). Method: Veterans with chronic PTSD who were medication-free or receiving stable pharmacotherapy were randomly assigned to guanfacine (N=29) versus placebo (N=34). Results: Guanfacine had no effect on PTSD symptoms, subjective sleep quality, or general mood disturbances. Guanfacine was associated with a number of side effects. Conclusions: These results do not support the use of alpha 2 agonists in veterans with chronic PTSD.
Merging pathology with biomechanics using CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration): a novel, surgery-free model of traumatic brain injury
Authors: Dhananjay R Namjoshi, Wai Hang Cheng, Kurt A McInnes, Kris M Martens, Michael Carr, Anna Wilkinson, Jianjia Fan, Jerome Robert, Arooj Hayat, Peter A Cripton, Cheryl L Wellington
Journal: Molecular Neurodegeneration (2014)

Traumatic brain injury (TBI) is a major health care concern that currently lacks any effective treatment. Despite promising outcomes from many preclinical studies, clinical evaluations have failed to identify effective pharmacological therapies, suggesting that the translational potential of preclinical models may require improvement. Rodents continue to be the most widely used species for preclinical TBI research. As most human TBIs result from impact to an intact skull, closed head injury (CHI) models are highly relevant, however, traditional CHI models suffer from extensive experimental variability that may be due to poor control over biomechanical inputs. Here we describe a novel CHI model called CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration) that fully integrates biomechanical, behavioral, and neuropathological analyses. CHIMERA is distinct from existing neurotrauma model systems in that it uses a completely non-surgical procedure to precisely deliver impacts of prescribed dynamic characteristics to a closed skull while enabling kinematic analysis of unconstrained head movement. In this study, we characterized head kinematics as well as functional, neuropathological, and biochemical outcomes up to 14d following repeated TBI (rTBI) in adult C57BL/6 mice using CHIMERA. Head kinematic analysis showed excellent repeatability over two closed head impacts separated at 24h. Injured mice showed significantly prolonged loss of righting reflex and displayed neurological, motor, and cognitive deficits along with anxiety-like behavior. Repeated TBI led to diffuse axonal injury with extensive microgliosis in white matter from 2-14d post-rTBI. Injured mouse brains also showed significantly increased levels of TNF-α and IL-1β and increased endogenous tau phosphorylation. Repeated TBI using CHIMERA mimics many of the functional and pathological characteristics of human TBI with a reliable biomechanical response of the head. This makes CHIMERA well suited to investigate the pathophysiology of TBI and for drug development programs.
The Organization and Reorganization of Human Speech Perception
Authors: J F Werker, R C Tees
Journal: Annual Review of Neuroscience (1992)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
A Randomized Prospective Trial to Assess the Impact of Transurethral Resection in Narrow Band Imaging Modality on Non–Muscle-Invasive Bladder Cancer Recurrence
Authors: Angelo Naselli, Carlo Introini, Luca Timossi, Bruno Spina, Vincenzo Fontana, Riccardo Pezzi, Francesco Germinale, Franco Bertolotto, Paolo Puppo
Journal: European Urology (2012)
Atypical Atrial Flutter Originating in the Right Atrial Free Wall
Authors: John G. Kall, Donald S. Rubenstein, Douglas E. Kopp, Martin C. Burke, Ralph J. Verdino, Albert C. Lin, C. Timothy Johnson, Philip A. Cooke, Zhong G. Wang, Michael Fumo, David J. Wilber
Journal: Circulation (2000)

Data from experimental models of atrial flutter indicate that macro-reentrant circuits may be confined by anatomic and functional barriers remote from the tricuspid annulus-eustachian ridge atrial isthmus. Data characterizing the various forms of atypical atrial flutter in humans are limited.In 6 of 160 consecutive patients referred for ablation of counterclockwise and/or clockwise typical atrial flutter, an additional atypical atrial flutter was mapped to the right atrial free wall. Five patients had no prior cardiac surgery. Incisional atrial tachycardia was excluded in the remaining patient. High-density electroanatomic maps of the reentrant circuit were obtained in 3 patients. Radiofrequency energy application from a discrete midlateral right atrial central line of conduction block to the inferior vena cava terminated and prevented the reinduction of atypical atrial flutter in each patient. Atrial flutter has not recurred in any patient (follow-up, 18+/-17 months; range, 3 to 40 months).Atrial flutter can arise in the right atrial free wall. This form of atypical atrial flutter could account for spontaneous or inducible atrial flutter observed in patients referred for ablation and is eliminated with linear ablation directed at the inferolateral right atrium.
Point: Universal Screening for Gestational Diabetes Mellitus
Authors: Robert G. Moses, N. Wah Cheung
Journal: Diabetes Care (2009)

Gestational diabetes mellitus (GDM) is one of the most common medical disorders found in pregnancy. Rates can range from 2 to >10%, and sometimes much higher, depending on the population being tested and the diagnostic criteria being used (1). The prevalence of GDM ultimately reflects the background rate of type 2 diabetes. There has also been an increase in the rate of GDM over the last generation, possibly related to community lifestyle factors as well as better case ascertainment (2,3).

### Significance of GDM

GDM is associated with a trilogy of risks. Significant pregnancy complications including increased perinatal morbidity and possibly mortality can occur (4,5). A diagnosis of GDM also identifies a mother at high risk for the future development of type 2 diabetes (1). The effects of maternal hyperglycemia (of any kind) are associated with the development of metabolic problems including type 2 diabetes in the offspring (6). It is, perhaps, for this effect of intrauterine programming that the disorder is most worthy of detection.

It has now been demonstrated that the treatment of GDM improves pregnancy outcomes. In the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS), the incidence of serious perinatal complications (a composite of death, shoulder dystocia, nerve palsy, and fracture) was 4% among women randomized to routine care compared with 1% among the intervention group (5). The number of GDM cases that needed to be treated to prevent one serious perinatal complication was 34. This indicates that excess serious perinatal complications will occur in 3% of cases of untreated or unrecognized GDM. This is a most compelling immediate argument for the screening of GDM given that the failure to identify a woman with GDM denies her the opportunity to have treatment for potentially preventable serious fetal complications.

### Why conduct selective screening for GDM?

Therefore, if we accept that GDM is …
Enhanced percutaneous absorption of a novel topical cyclosporin A formulation and assessment of its immunosuppressive activity
Authors: J.I. DUNCAN, S.N.L. PAYNE, A.J. WINFIELD, A.D. ORMEROD, A.W. THOMSON
Journal: British Journal of Dermatology (1990)

No clinically successful topical cyclosporin A (CyA) formulation has been produced, mainly due to the apparent lack of drug penetration. This study has produced the first in vitro kinetic data on CyA penetration across human cadavar stratum corneum and has shown that addition of the penetration enhancers (PE) Azone and propylene glycol to the CyA vehicle significantly enhanced drug permeation across the skin barrier. Using flow-through permeability cells with 5% w/v CyA (Sandimmun®) alone (CyA) or with PE (CyA+PE) in olive oil in the donor chamber, the penetration rate (mean ± SD μg/cm2/h) into receptor fluid was 53 ± 43 (n=13) for CyA and 660±175 (n=7) for CyA+PE. The in vivo efficacy of this formulation was assessed in guinea-pigs undergoing delayed-type hypersensitivity (DTH) reactions to dinitrofluorobenzene (DNFB). CyA was applied topically at the time of challenge and twice daily thereafter. At 24 h, skin reactions revealed that compared with appropriate drug vehicles, concentrations of 0.25, 0.5 and 5% CyA±PE had a significant inhibitory effect upon the erythema response and this corresponded with significant reductions in T-cell infiltrates (0.5 and 5% CyA). No statistically significant reductions in erythema were demonstrated with 0.05% CyA±PE, but there was a reduction in the number of infiltrating lymphocytes in sites receiving 0.05% CyA+PE compared with vehicle-treated sites (P<0.01). This suggests that PE permitted some penetration of an otherwise non-immunosuppressive concentration of CyA through the skin.
Intensity-modulated radiation therapy leads to survival benefit only in patients with high-risk prostate cancer: a population-based study
Authors: G. Gandaglia, P.I. Karakiewicz, A. Briganti, Q.D. Trinh, J. Schiffmann, Z. Tian, S.P. Kim, P.L. Nguyen, M. Graefen, F. Montorsi, M. Sun, F. Abdollah
Journal: Annals of Oncology (2014)
High-intensity interval training improves microvascular and macrovascular function and insulin sensitivity
Authors: M Cocks, S O Shepherd, K D Tipton, A J M Wagenmakers, C S Shaw
Journal: British Journal of Sports Medicine (2010)

Both micro and macrovascular adaptations contribute to the mechanisms by which reduced physical activity increases the risk for cardiovascular disease and insulin resistance. In a parallel abstract,1 the authors report that 6 weeks of high-intensity interval training (HIT) improves insulin sensitivity. Here the authors aim to investigate whether changes in vascular function play a potential role in this improvement of insulin sensitivity. Eight, young sedentary males (age: 23±2 years, BMI 24.5±1.5 Kg/m 2 ) took part in 6 weeks of HIT involving four to six, 30-s Wingate tests separated by 4.5 min of recovery, performed three times per week. Calf microvascular filtration capacity (Kf) which is an indirect measure of muscle capillary density, was measured using venous occlusion plethysmography. Arterial stiffness was assessed using applanation tonometry (SphygmoCor) to determine peripheral (PPWV) and central pulse wave velocity (CPWV), and augmentation index normalised to 75 beats per minute (AIx at 75 bpm). Blood pressure and insulin sensitivity (oral glucose tolerance test) were also measured pre and post training. Calf microvascular Kf improved after training by 43% (2.81±0.30 ml/min vs 4.02±0.70 ml/min 100 ml/mm Hg×10 −3 ; p&lt;0.05). CPWV and PPWV showed a trend to decrease after training (CPWV 4.8±0.3 m/s vs 4.5±0.3 m/s; p=0.053, PPWV 6.4±0.6 m/s vs 5.9±0.4 m/s; p=0.098). No significant change was observed in AIx at 75 bpm (p=0.114). Resting systolic and diastolic BP decreased after training (systolic 119±2 mm Hg vs 114±2 mm Hg; p&lt;0.05, diastolic 63±3 mm Hg vs 59±2 mm Hg; p&lt;0.05). In the parallel study the authors observe increases in insulin sensitivity. The authors conclude that low volume HIT is an effective method to elicit improvements in both micro and macrovascular function which are likely to be mechanistically related to the observed improvements in insulin sensitivity.
Website of the week: Medical history
Authors: T. Jackson
Journal: BMJ (2002)

Roy Porter, the greatest medical historian of his generation, whose obituary appears in this week's BMJ (p 680), reminded “the medical profession of the richness and relevance of its history.” But where would you start if you wanted to find out about some aspect of the medical past? The concept of historical research is redolent of musty books and dusty archives, collections of curios and card index files. That is until you try typing “medical history” into a search engine such as Google. My initial search found 350,000 results, some of these, admittedly, connected with patient history taking. But there are enormous online libraries (www.usuhs.mil/meh/histres.html), virtual museums (www.cwru.edu/artsci/dittrick/linkspages/musoverseas.htm), picture archives (wwwihm.nlm.nih.gov/), and medical milestones pages (http://faculty.washington.edu/chudler/hist.html). Some of these sites are as unconventional as Roy Porter's earrings (for example, the Museum of Questionable Medical Devices at www.mtn.org/∼quack/).

Probably the three best places to start are the United States National Library of Medicine (www.nlm.nih.gov/), the Wellcome Trust Centre for the History of Medicine (www.wellcome.ac.uk/en/1/homwtc.html), and the Royal Society of Medicine (www.roysocmed.ac.uk/), which has one of the largest postgraduate biomedical libraries in Europe, with a total collection of half a million volumes dating back to the 15th century. All have searchable online catalogues, but although you won't be able to read any books online, you will be able to get an idea of what has been published where and when. Both the National Library of Medicine and Wellcome have huge searchable image archives, but only at the National Library of Medicine, which is the largest medical library in the world and creator of Medline/PubMed, is it possible to call up images online (wwwihm.nlm.nih.gov/). From lithographs of Edward Jenner to one of the first US posters promoting the MMR (measles, mumps, rubella) vaccine, the visual history of medicine seems here as rich and relevant as Roy Porter believed.

Elsewhere on the internet, there are several valuable links pages of medical historical resources (for example, www.mla-hhss.org/histlink.htm and www.anes.uab.edu/aneshist/anesnet.htm). The rest, as they say, is history.
Nomograms Provide Improved Accuracy for Predicting Survival after Radical Cystectomy
Authors: Shahrokh F. Shariat, Pierre I. Karakiewicz, Ganesh S. Palapattu, Gilad E. Amiel, Yair Lotan, Craig G. Rogers, Amnon Vazina, Patrick J. Bastian, Amit Gupta, Arthur I. Sagalowsky, Mark Schoenberg, Seth P. Lerner
Journal: Clinical Cancer Research (2006)

Abstract Aims: To develop multivariate nomograms that determine the probabilities of all-cause and bladder cancer–specific survival after radical cystectomy and to compare their predictive accuracy to that of American Joint Committee on Cancer (AJCC) staging. Methods: We used Cox proportional hazards regression analyses to model variables of 731 consecutive patients treated with radical cystectomy and bilateral pelvic lymphadenectomy for bladder transitional cell carcinoma. Variables included age of patient, gender, pathologic stage (pT), pathologic grade, carcinoma in situ, lymphovascular invasion (LVI), lymph node status (pN), neoadjuvant chemotherapy (NACH), adjuvant chemotherapy (ACH), and adjuvant external beam radiotherapy (AXRT). Two hundred bootstrap resamples were used to reduce overfit bias and for internal validation. Results: During a mean follow-up of 36.4 months, 290 of 731 (39.7%) patients died; 196 of 290 patients (67.6%) died of bladder cancer. Actuarial all-cause survival estimates were 56.3% [95% confidence interval (95% CI), 51.8-60.6%] and 42.9% (95% CI, 37.3-48.4%) at 5 and 8 years after cystectomy, respectively. Actuarial cancer-specific survival estimates were 67.3% (62.9-71.3%) and 58.7% (52.7-64.2%) at 5 and 8 years, respectively. The accuracy of a nomogram for prediction of all-cause survival (0.732) that included patient age, pT, pN, LVI, NACH, ACH, and AXRT was significantly superior (P = 0.001) to that of AJCC staging–based risk grouping (0.615). Similarly, the accuracy of a nomogram for prediction of cancer-specific survival that included pT, pN, LVI, NACH, and AXRT (0.791) was significantly superior (P = 0.001) to that of AJCC staging–based risk grouping (0.663). Conclusions: Multivariate nomograms provide a more accurate and relevant individualized prediction of survival after cystectomy compared with conventional prediction models, thereby allowing for improved patient counseling and treatment selection.
Untreated Rejection in 6-Month Protocol Biopsies Is Not Associated with Fibrosis in Serial Biopsies or with Loss of Graft Function
Authors: Eduard M. Scholten, Ajda T. Rowshani, Serge Cremers, Frederike J. Bemelman, Michael Eikmans, Erik van Kan, Marko J. Mallat, Sandrine Florquin, Janto Surachno, Ineke J. ten Berge, Ingeborg M. Bajema, Johan W. de Fijter
Journal: Journal of the American Society of Nephrology (2006)

Donor age, calcineurin inhibitor nephrotoxicity, and acute rejection are the most significant predictors of chronic allograft nephropathy. Protocol biopsies, both in deceased- and living-donor renal grafts, have shown that cortical tubulointerstitial fibrosis correlates with graft survival and function. The impact of not treating subclinical acute rejection (SAR) is less clear. In this study, 126 de novo renal transplant recipients were randomly assigned to receive area-under-the-curve–controlled exposure of either a cyclosporine or a tacrolimus-based immunosuppressive regimen that included steroids, mycophenolate mofetil, and basiliximab induction. Protocol biopsies were taken before and 6 and 12 mo after transplantation. The prevalence of SAR was determined retrospectively. Fibrosis was evaluated by quantitative digital analysis of Sirius red staining in serial biopsies. Donor age correlated significantly with tubulointerstitial fibrosis in pretransplantation biopsies and inferior graft function at month 6 (rτ = −0.26; P = 0.033). Acute rejection incidence was 11.5%, and no clinical late rejection occurred. The prevalence of SAR at 6 mo was 30.8% but was not associated with differences in serial quantitative Sirius red staining at 6 or 12 mo, proteinuria, or progressive loss of GFR up to 2 yr. No differences were found in donor variables, histocompatibility, rejection history, or exposure of immunosuppressants. Controlled individualized calcineurin inhibitor exposure and subsequent tapering resulted in a low early acute rejection rate and prevented late acute rejection. Because, by design, we did not treat SAR, these results provide evidence that asymptomatic infiltrates in 6-mo surveillance biopsies may not be deleterious in the intermediate term. There is need for reliable biomarkers to prove that not all cell infiltrates are equivalent or that infiltrates may change with time.
No quiet surrender: molecular guardians in multiple sclerosis brain
Authors: Lawrence Steinman
Journal: Journal of Clinical Investigation (2015)

The brain under immunological attack does not surrender quietly. Investigation of brain lesions in multiple sclerosis (MS) reveals a coordinated molecular response involving various proteins and small molecules ranging from heat shock proteins to small lipids, neurotransmitters, and even gases, which provide protection and foster repair. Reduction of inflammation serves as a necessary prerequisite for effective recovery and regeneration. Remarkably, many lesion-resident molecules activate pathways leading to both suppression of inflammation and promotion of repair mechanisms. These guardian molecules and their corresponding physiologic pathways could potentially be exploited to silence inflammation and repair the injured and degenerating brain and spinal cord in both relapsing-remitting and progressive forms of MS and may be beneficial in other neurologic and psychiatric conditions.
A German multicenter, randomized phase III trial comparing irinotecan–carboplatin with etoposide–carboplatin as first-line therapy for extensive-disease small-cell lung cancer
Authors: A. Schmittel, M. Sebastian, L. Fischer von Weikersthal, P. Martus, T.C. Gauler, C. Kaufmann, P. Hortig, J.R. Fischer, H. Link, D. Binder, B. Fischer, K. Caca, W.E.E. Eberhardt, U. Keilholz
Journal: Annals of Oncology (2011)

BackgroundThis trial was designed to prove superiority of irinotecan over etoposide combined with carboplatin in extensive-disease small-cell lung cancer.Patients and methodsPatients were randomly assigned to receive carboplatin area under the curve 5 mg ·min/ml either in combination with irinotecan 50 mg/m2 on days 1, 8, and 15 (IP) or etoposide 140 mg/m2 on days 1–3 (EP). Primary end point was progression-free survival (PFS) at 6 months. Secondary end points were overall survival (OS), response rate, and toxicity.ResultsOf 226 patients, 216 were eligible. Median PFS was 6.0 months [95% confidence interval (CI) 5.0–7.0] in the IP arm and 6.0 months (95% CI 5.2–6.8) in EP arm (P = 0.07). Median survival was 10.0 months (95% CI 8.4–11.6) and 9.0 months (95% CI 7.6–10.4) in the IP and EP arm (P = 0.06), respectively. Hazard ratios for disease progression and OS were 1.29 (95% CI 0.96–1.73, P = 0.095) and 1.34 (95% CI 0.97–1.85, P = 0.072), respectively. No difference in response rates was observed. Grade 3 and 4 hematologic toxicity favored the IP arm, whereas diarrhea was significantly more frequent in the IP arm.ConclusionThis trial failed to show superiority of irinotecan over etoposide in combination with carboplatin.