tbuckley/cabot-search huggingface dataset:
CONSERVATIVE TREATMENT OF TOTAL PROXIMAL, NON-AVULSION, HAMSTRING MUSCLE - RUPTURE, IN HIGH LEVEL ATHLETES
Authors: Nikos Malliaropoulos, Panagiotis Psyllakis, Kostas Tsitas, Agapi Papalada
Journal: British Journal of Sports Medicine (2013)

Background Hamstring muscle injuries are notoriously found among the most common causes of abstinence and delayed return to sport, in a variety of track, field and other high level athletes. In this respect we present our experience of conservative treatment of total proximal, non-avulsed hamstring rupture in high-level track, field and other athletes and application of an integrated rehabilitation protocol. Methods Eleven high level athletes, nine men and two women, were diagnosed with sub/ total proximal, non-avulsed, hamstring rupture (grade III or IV strain). All of the patients were treated conservatively over a time scheme of twelve weeks.Then the athletes were ready to return to their complete sport–specific training. Results All the athletes were treated conservatively. All of them made a full return to their sport .Mean follow up time was from six months to two years. One male track athlete had a multiple reinjury history after his primary hamstring rupture (over 18 months of follow up).All the other athletes fully returned to their sports with no recurrent hamstring injuries during the follow up. Conclusions Indications that have been proposed for operative treatment of total proximal hamstring ruptures are most clear and widely acceptable when a bone avulsion is present off the ischial tuberosity. 1 However when it comes to total proximal, non avulsed ,hamstring rupture (grade III or IV strain) the operative indications may be relative and there still may be a place for integrated conservative treatment. 2 Conservative treatment has to be based on the correct classification of the injury, the right clinical assessment at the acute phase as well as along the whole length of treatment. Surgical treatment has an important role to play in complete proximal hamstring ruptures bearing in mind the right indications such as acute bone avulsions from the muscles’ origin. 3
High-Dose Atorvastatin Improves Hypercholesterolemic Coronary Endothelial Dysfunction Without Improving the Angiogenic Response
Authors: Munir Boodhwani, Yasunari Nakai, Pierre Voisine, Jun Feng, Jian Li, Shigetoshi Mieno, Basel Ramlawi, Cesario Bianchi, Roger Laham, Frank W. Sellke
Journal: Circulation (2006)

Background— Although 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) can restore endothelial function in coronary disease, in vitro and murine studies have shown their effects on myocardial angiogenesis to be biphasic and dose dependent. We investigated the functional and molecular effects of high-dose atorvastatin on the endogenous angiogenic response to chronic myocardial ischemia in hypercholesterolemic swine. Methods and Results— Yucatan pigs were fed either a normal (NORM group; n=7) or high-cholesterol diet, with (CHOL-ATR group; n=7) or without (CHOL group; n=6) atorvastatin (3 mg/kg per day) for 13 weeks. Chronic ischemia was induced by ameroid constrictor placement around the circumflex artery. Seven weeks later, microvessel relaxation responses, myocardial perfusion, and myocardial protein expression were assessed. The CHOL group demonstrated impaired microvessel relaxation to adenosine diphosphate (29±3% versus 61±6%, CHOL versus NORM; P &lt;0.05), which was normalized in the CHOL-ATR group (67±2%; P =NS versus NORM). Collateral-dependent myocardial perfusion, adjusted for baseline, was significantly reduced in the CHOL group (−0.27±0.07 mL/min per gram versus NORM; P &lt;0.001) as well as the CHOL-ATR group (−0.35±0.07 mL/min per gram versus NORM; P &lt;0.001). Atorvastatin treatment was associated with increased phosphorylation of Akt (5.7-fold increase versus NORM; P =0.001), decreased vascular endothelial growth factor expression (−68±8%; P &lt;0.001 versus NORM), and increased expression of the antiangiogenic protein endostatin (210±48%; P =0.004 versus NORM). Conclusions— Atorvastatin improves hypercholesterolemia-induced endothelial dysfunction without appreciable changes in collateral-dependent perfusion. Increased myocardial expression of endostatin, decreased expression of vascular endothelial growth factor, and chronic Akt activation associated with atorvastatin treatment may account for the diminished angiogenic response.
Factors Associated With Initial Therapy for Clinically Localized Prostate Cancer: Prostate Cancer Outcomes Study
Authors: L. C. Harlan, A. Potosky, F. D. Gilliland, R. Hoffman, P. C. Albertsen, A. S. Hamilton, J. W. Eley, J. L. Stanford, R. A. Stephenson
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Because of the lack of results from randomized clinical trials comparing the efficacy of aggressive therapies with that of more conservative therapies for clinically localized prostate cancer, men and their physicians may select treatments based on other criteria. We examined the association of sociodemographic and clinical characteristics with four management options: radical prostatectomy, radiation therapy, hormonal therapy, and watchful waiting. Methods: We studied 3073 participants of the Prostate Cancer Outcomes Study diagnosed from October 1, 1994, through October 31, 1995, with clinically localized disease (T1 or T2). Participants completed a baseline survey, and diagnostic and treatment information was abstracted from medical records. Multiple logistic regression analysis identified factors associated with initial treatment. All statistical tests were two-sided. Results: Patients with clinically localized disease received the following treatments: radical prostatectomy (47.6%), radiation therapy (23.4%), hormonal therapy (10.5%), or watchful waiting (18.5%). Men aged 75 years or older more often received conservative treatment (i.e., hormonal therapy alone or watchful waiting; 57.9% of men aged 75–79 years and 82.1% of men aged 80 years and older) than aggressive treatment (i.e., radical prostatectomy or radiation therapy) (for all age groups, P≤.001). After adjustment for age, clinical stage, baseline prostate-specific antigen level, and histologic grade, the following factors were associated with conservative treatment: history of a heart attack, being unmarried, geographic region, poor pretreatment bladder control, and impotence. In men younger than 60 years, use of aggressive treatment was similar by race/ethnicity (adjusted percentages = 85.5%, 88.1%, and 85.3% for white, African-American, and Hispanic men, respectively). However, among men 60 years old and older, African-American men underwent aggressive treatment less often than did white men or Hispanic men (adjusted percentages for men aged 60–64 years = 67.1%, 84.7%, and 79.2%, respectively; 65–74 years = 64.8%, 73.4%, and 79.5%, respectively; and 75 years old and older = 25.2%, 45.7%, and 36.6%, respectively). Conclusions: The association of nonclinical factors with treatment suggests that, in the absence of definitive information regarding treatment effectiveness, men diagnosed with prostate cancer should be better informed of the risks and benefits of all treatment options.
A Study of Some Failures in Methadone Treatment
Authors: MARVIN E. PERKINS, HARRIET I. BLOCH
Journal: American Journal of Psychiatry (1971)

The authors conducted a follow-up survey of 66 patients who had dropped out of a methadone maintenance program. Six had died since discharge. Of the 53 who were located and interviewed, 34 had been hospitalized for physical or mental conditions or for detoxification. Though 13 had not been arrested since discharge, the others accounted for more than 110 arrests, 78 incarcerations, and 63 convictions. Except among the 15 who were then institutionalized, with abstinence enforced, the use of heroin continued to be a dominant activity: only two were in methadone programs and only two had been abstinent for a significant length of time. The authors believe that there should be a greater effort to retain addicts in methadone programs in order to improve their chances of rehabilitation.
Hepatitis C minimal residual viremia (MRV) detected by TMA at the end of Peg-IFN plus ribavirin therapy predicts post-treatment relapse
Authors: Martina Gerotto, Francesca Dal Pero, Gladis Bortoletto, Alessia Ferrari, Roberta Pistis, Giada Sebastiani, Stefano Fagiuoli, Stefano Realdon, Alfredo Alberti
Journal: Journal of Hepatology (2005)

Around 15-25% of chronic hepatitis C patients treated with Peg-IFN plus ribavirin become HCV-RNA negative by PCR during therapy but relapse after its withdrawal. We investigated whether minimal residual viremia (MRV) might be detected in these cases by Transcription-Mediated Amplification (TMA).Two hundred and ninety-two consecutive patients (143 HCV-1, 82 HCV-2, 56 HCV-3 and 11 HCV-4) were prospectively treated with a standard schedule of Peg-IFNalpha 2b plus ribavirin combination and end-of-therapy response was assessed by conventional PCR using 2 protocol serum samples obtained 6-8h before the last two scheduled weekly injections of Peg-IFN. PCR negative samples were re-tested by TMA and the results were then correlated with the virological outcome after therapy withdrawal.Among 208 patients who were repeatedly HCV-RNA negative by PCR at the end-of-therapy, 26 (12.5%) were found HCV-RNA positive by TMA. Twenty-two of them, (96%) were PCR-relapsers after therapy withdrawal, compared to only 14% of the 182 TMA negative patients (P<0.0001). This virological profile was more frequent in HCV-1 and HCV-3 infected patients and correlated with a slower virological response during therapy.At the end of Peg-IFN plus ribavirin therapy, TMA is superior to PCR in identifying patients with sustained HCV-RNA clearance.
Serum Insulin Levels and the Prevalence of Adenomatous and Hyperplastic Polyps in the Proximal Colon
Authors: Isao Yoshida, Ayako Suzuki, Marc Vallée, Yutaka Matano, Takaharu Masunaga, Takahiro Zenda, Kimihide Shinozaki, Toshihide Okada
Journal: Clinical Gastroenterology and Hepatology (2006)
Self-assessment in medical practice
Authors: A W Evans, C McKenna, M Oliver
Journal: Journal of the Royal Society of Medicine (2002)

Although assessment of performance will be central to revalidation, to clinical governance and to maintenance of quality in the National Health Service, formal appraisal by a third party will be no more than an annual event for most medical staff. To be fully effective doctors should assess their own clinical performance more frequently, but many lack training in how to do this. Self-assessment is also a valuable exercise in its own right. Benefits include increased morale and motivation as well as improvements in knowledge, communication and performance1. This paper sets out the case for devoting more time to the teaching of self-assessment skills.
Thorax in the 1980s
Authors: R A L Brewis
Journal: Thorax (2006)

Reflecting on the experience of editing Thorax , now more than 20 years ago, what stands out in the memory is not any individual ground breaking paper but rather an impression of the huge variety of topics which clamoured for attention under the thoracic banner, and of the general mood of enthusiasm and cooperation which prevailed at the time.

By the early 1980s respiratory medicine had broadened out from its earlier essential focus on tuberculosis and industrial lung disease and seemed at last to have an established position within general medicine. Bright young academic minds were increasingly attracted to the specialty and the quantity and quality of research were advancing in proportion. The British Thoracic Society was newly formed and had confirmed Thorax as its official organ. The general enthusiasm for the subject clearly evident in the Society’s meetings was transmitted to the journal. Specialists from a rapidly widening variety of clinical disciplines and basic sciences contributed to the submitted papers, and there was a steady increase in submissions from overseas. Thoracic surgery with its more direct links to cardiology was also changing in character but maintained a strong presence and, up …
Inotropic actions of isoproterenol in cat ventricular muscle. Effects of extracellular potassium.
Authors: J R Wiggins
Journal: Circulation Research (1981)

The inotropic actions of isoproterenol in cat papillary muscles or trabeculae bathed in a salt solution containing 4 mM KCl were compared to those in similar muscles bathed in a salt solution containing 22 mM KC1. Although isoproterenol evoked the same increase in force of contraction in both groups of muscles, the time course of contraction differed markedly. In muscles bathed in 4 mM KC1, isoproterenol caused a concentration-dependent decrease in time-to-peak force, but in muscles bathed in 22 mM KCl, isoproterenol caused a concentration-dependent increase in time-to-peak force. These data suggest that ventricular muscle activated by slow response action potentials may utilize a different mechanism of excitation-contraction coupling than do muscles activated by Na-dependent action potentials.
Effects of MicroRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma
Authors: Yujuan Xiong, Jian-Hong Fang, Jing-Ping Yun, Jine Yang, Ying Zhang, Wei-Hua Jia, Shi-Mei Zhuang
Journal: Hepatology (2009)

Based on microarray data, we have previously shown a significant down-regulation of miR-29 in hepatocellular carcinoma (HCC) tissues. To date, the role of miR-29 deregulation in hepatocarcinogenesis and the signaling pathways by which miR-29 exerts its function and modulates the malignant phenotypes of HCC cells remain largely unknown. In this study, we confirmed that reduced expression of miR-29 was a frequent event in HCC tissues using both Northern blot and real-time quantitative reverse-transcription polymerase chain reaction. More interestingly, we found that miR-29 down-regulation was significantly associated with worse disease-free survival of HCC patients. Both gain- and loss-of-function studies revealed that miR-29 could sensitize HCC cells to apoptosis that was triggered by either serum starvation and hypoxia or chemotherapeutic drugs, which mimicked the tumor growth environment in vivo and the clinical treatment. Moreover, introduction of miR-29 dramatically repressed the ability of HCC cells to form tumor in nude mice. Subsequent investigation characterized two antiapoptotic molecules, Bcl-2 and Mcl-1, as direct targets of miR-29. Furthermore, silencing of Bcl-2 and Mcl-1 phenocopied the proapoptotic effect of miR-29, whereas overexpression of these proteins attenuated the effect of miR-29. In addition, enhanced expression of miR-29 resulted in the loss of mitochondrial potential and the release of cytochrome c to cytoplasm, suggesting that miR-29 may promote apoptosis through a mitochondrial pathway that involves Mcl-1 and Bcl-2. Conclusion: Our data highlight an important role of miR-29 in the regulation of apoptosis and in the molecular etiology of HCC, and implicate the potential application of miR-29 in prognosis prediction and in cancer therapy. (Hepatology 2010.)
A Novel Fusion Toxin Derived from an EpCAM-Specific Designed Ankyrin Repeat Protein Has Potent Antitumor Activity
Authors: Patricia Martin-Killias, Nikolas Stefan, Sacha Rothschild, Andreas Plückthun, Uwe Zangemeister-Wittke
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Designed ankyrin repeat proteins (DARPins) hold great promise as a new class of binding molecules to overcome the limitations of antibodies for biomedical applications. Here, we assessed the potential of an epithelial cell adhesion molecule (EpCAM)–specific DARPin (Ec4) for tumor targeting as a fusion toxin with Pseudomonas aeruginosa exotoxin A. Experimental design: DARPin Ec4 was genetically fused to a truncated form of Pseudomonas aeruginosa exotoxin A (ETA″) and expressed in Escherichia coli. The cytotoxicity of Ec4-ETA″ was measured against tumor cell lines of various histotypes in vitro. Tumor localization and antitumor activity were determined in mice bearing 2 different EpCAM-positive tumor xenografts. Results: Ec4-ETA″ expressed very well in soluble form in the cytoplasm of E. coli and yielded up to 40 mg after purification per liter of culture. The protein was monomeric and the disulfides of ETA″ formed spontaneously. Ec4-ETA″ bound to EpCAM with low nanomolar affinity, similar to free Ec4. Furthermore, it was highly cytotoxic against various EpCAM-positive tumor cell lines in vitro with IC50 values less than 0.005 pmol/L. This effect was competed by free Ec4, but not by unspecific DARPins. Upon systemic administration in athymic mice, Ec4-ETA″ efficiently localized to EpCAM-positive tumors to achieve maximum accumulation 48 to 72 hours after injection, whereas an irrelevant control fusion toxin did not accumulate. Tumor targeting with Ec4-ETA″ resulted in a strong antitumor response including complete regressions in some animals. Conclusions: Our data show for the first time the potential of DARPins for the generation of protein therapeutics for tumor targeting, and that Ec4-ETA″ deserves attention for clinical development. Clin Cancer Res; 17(1); 100–10. ©2010 AACR.
Comparative, continuity, and computational evidence in evolutionary theory: Predictive evidence versus productive evidence
Authors: David M. W. Powers
Journal: Behavioral and Brain Sciences (2006)

Of three types of evidence available to evolution theorists – comparative, continuity, and computational – the first is largely productive rather than predictive. Although comparison between extant species or languages is possible and can be suggestive of evolutionary processes, leading to theory development, comparison with extinct species and languages seems necessary for validation. Continuity and computational evidence provide the best opportunities for supporting predictions.
Noninvasive 24-hour ambulatory arterial blood pressure monitoring in cirrhosis
Authors: Søren Møller, Niels Wiinberg, Jens H. Henriksen
Journal: Hepatology (1995)

Cirrhotic patients have disturbed systemic hemodynamics with reduced arterial blood pressure, but this has not been investigated during daily activity and sleep. Systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MAP), and heart rate (HR) were measured by an automatic ambulant device for monitoring blood pressure in 35 patients with cirrhosis and 35 healthy matched controls. During the daytime, SBP, DBP, and MAP were significantly lower in the patients than in the controls (median 118 vs. 127; 70 vs. 78; 86 vs. 94 mm Hg, P < .0001 to P < .05). The nighttime blood pressures were almost similar in the two groups (108 vs. 110; 65 vs. 67; 78 vs. 82 mm Hg, NS). Conversely, HR was significantly higher in the patients both in the daytime (86 vs. 72/min, P < .0001) and at night (80 vs. 64/min, P < .0001). Consequently, the reduction in blood pressure and HR from daytime to nighttime was significantly lower in the patients than in the controls (P < .0001 to P < .01). Multiple regression analysis showed HR, serum albumin, serum sodium, and clotting factors 2, 7, and 10 as significant independent predictors of SBP in cirrhosis. In conclusion, cirrhotic patients have elevated HR, but surprisingly normal arterial blood pressure during the nighttime, and the circadian variation in blood pressure and HR is diminished, probably because of an almost unaltered cardiac output during the 24 hours. These results may reflect a major defect in the ability of optimal regulation of blood pressure in cirrhotic patients.
<i>Burkholderia cepacia</i>: current clinical issues, environmental controversies and ethical dilemmas
Authors: A.M. Jones, M.E. Dodd, A.K. Webb
Journal: European Respiratory Journal (2001)

Burkholderia cepacia is a plant phytogen and is known as a hardy and versatile organism. Over the past two decades it has emerged as a pathogen in the cystic fibrosis (CF) community, with devastating effects. Pulmonary colonisation can lead to an accelerated decline in lung function. In some cases, it causes a rapid and progressive pneumonic illness termed “ cepacia syndrome”, which is untreatable and fatal. B. cepacia is inherently resistant to multiple antibiotics and highly transmissible and virulent strains have been identified. CF patients colonised with the organism have to be segregated from their peers to try to prevent cross-infection. However, the pathogenicity of B. cepacia is not limited to CF. Other groups, such as individuals with chronic granulomatous disease and immunocompromised patients are vulnerable and it has caused disease in healthy individuals. However, the agricultural and petrochemical industries are attempting to exploit properties of B. cepacia for use as a biopesticide and biodegradation agent. This article provides an up to date review of clinically based literature on the Burkholderia cepacia complex, highlighting clinical management issues for both cystic fibrosis and non-cystic fibrosis patients. The article also addresses the potential conflict between medicine and agriculture on plans to reintroduce strains of Burkholderia cepacia back into the environment.
Multiple Myeloma: New Uses for Available Agents, Excitement for the Future
Authors: Kenneth C. Anderson
Journal: Journal of the National Comprehensive Cancer Network (2015)

With the availability of a new proteasome inhibitor, carfilzomib, and a new immunomodulatory drug, pomalidomide, the treatment of multiple myeloma has become more effective. The updated NCCN Clinical Practice Guidelines in Oncology for Multiple Myeloma provide new recommendations for use of carfilzomib and pomalidomide. As new classes of drugs such as monoclonal antibodies become available, the treatment landscape will be rendered even brighter.