tbuckley/cabot-search huggingface dataset:
Breast Cancer After Use of Estrogen Plus Progestin and Estrogen Alone
Authors: Rowan T. Chlebowski, Thomas E. Rohan, JoAnn E. Manson, Aaron K. Aragaki, Andrew Kaunitz, Marcia L. Stefanick, Michael S. Simon, Karen C. Johnson, Jean Wactawski-Wende, Mary J. O’Sullivan, Lucile L. Adams-Campbell, Rami Nassir, Lawrence S. Lessin, Ross L. Prentice
Journal: JAMA Oncology (2015)

The use of menopausal hormone therapy (HT) continues in clinical practice, but reports are conflicting concerning the longer-term breast cancer effects of relatively short-term use.To report the longer-term influence of menopausal HT on breast cancer incidence in the 2 Women's Health Initiative (WHI) randomized clinical trials.A total of 27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers from 1993 to 1998 and followed up for a median of 13 years through September 2010.A total of 16,608 women with a uterus were randomized to conjugated equine estrogens (0.625 mg/d [estrogen]) plus medroxyprogesterone acetate (2.5 mg/d [progestin]) (E + P) or placebo with a median intervention duration of 5.6 years, and 10,739 women with prior hysterectomy were randomized to conjugated equine estrogens alone (0.625 mg/d) or placebo with a median intervention duration of 7.2 years.Time-specific invasive breast cancer incidence rates and exploratory analyses of breast cancer characteristics by intervention and postintervention phases in the 2 HT trials.In the E + P trial, hazard ratios (HRs) for the influence of combined HT on breast cancer were lower than 1 for 2 years (HR, 0.71; 95% CI, 0.47-1.08) and steadily increased throughout intervention, becoming significantly increased for the entire intervention phase (HR, 1.24; 95% CI, 1.01-1.53). In the early postintervention phase (within 2.75 years from intervention), there was a sharp decrease in breast cancer incidence in the combined HT group, though the HR remained higher than 1 (HR, 1.23; 95% CI, 0.90-1.70). During the late postintervention phase (requiring patient re-consent), the HR for breast cancer risk remained higher than 1 through 5.5 years (median) of additional follow-up (HR, 1.37; 95% CI, 1.06-1.77). In the estrogen alone trial, the HR for invasive breast cancer risk was lower than 1 throughout the intervention phase (HR, 0.79; 95% CI, 0.61-1.02) and remained lower than 1 in the early postintervention phase (HR, 0.55; 95% CI, 0.34-0.89), but risk reduction was not observed during the late postintervention follow-up (HR, 1.17; 95% CI, 0.73-1.87). Characteristics of breast cancers diagnosed during early and late postintervention phases differed in both trials.In the E + P trial, the higher breast cancer risk seen during intervention was followed by a substantial drop in risk in the early postintervention phase, but a higher breast cancer risk remained during the late postintervention follow-up. In the estrogen alone trial, the lower breast cancer risk seen during intervention was sustained in the early postintervention phase but was not evident during the late postintervention follow-up.
THE EPIDEMIOLOGY OF INJURIES IN CONTACT FLAG FOOTBALL
Authors: Y Kaplan, E Witvrouw, G Myklebust, M Nyska, E Palmanovich, J Victor
Journal: British Journal of Sports Medicine (2014)

Background American Flag football (AFF) is a version of American Football that has become very popular worldwide, but lacks high quality research into the epidemiology of injuries. Objective To characterize the epidemiology of injuries in post–high school male and female athletes in the rapidly growing international sport of contact flag football. Design Prospective injury-observational study. Setting Kraft Stadium, Jerusalem, Israel. Participants 1 492 players,consisting of men (n=1 252, mean age, 20.49±5.11) and women (n=240, mean age, 21.32±8.95 years), participated in 1028 games over a 2-season period (2007–2009). Main outcome measures All time-loss injuries sustained in game sessions were recorded by the off-the-field medical personnel and followed up by a more detailed phone injury surveillance questionnaire. Results One hundred sixty-three injuries were reported, comprising 1 533 776 athletic exposures (AEs). The incidence rate was 0.11 [95% confidence interval (CI), 0.09–0.12] per 1000 AEs, and incidence proportion was 10.66% (95% CI, 9.10–12.22). Seventy-six percent of the injuries were extrinsic in nature. Thirty percent of the injuries were to the fingers, thumb, and wrist, 17% to the knee, 17% to the head/face, 13% to the ankle, and 11% to the shoulder. Conclusions Contact flag football results in a significant amount of moderate to severe injuries. These data may be used in the development of a formal American flag football injury database and in the development and implementation of a high-quality, randomized, prospective injury prevention study. This study should include the enforcement of the no-pocket rule, appropriate headgear, self-fitting mouth guards, the use of ankle braces, and changing the blocking rules of the game.
Lung Inflammation in ARDS — Friend or Foe?
Authors: Peter M. Suter
Journal: New England Journal of Medicine (2006)

There is good reason that treatment of the acute respiratory distress syndrome (ARDS) with corticosteroids has been a much-studied subject. In response to a number of serious underlying events, such as sepsis, inhalation of gastric contents, and multiple trauma, the body reacts with acute inflammation of the lung parenchyma — a process that is characterized by increased vascular permeability, extravasation of plasma, and leukocyte infiltration; this combination of events is known as ARDS. This illness has an early acute phase that affects all patients; a variable fraction have a late phase, characterized by pulmonary fibrosis. Management of either phase of . . .
Multiple mantleomas: an unusual clinical presentation of an intriguing tumour
Authors: A.-M. Thielen, J.-L. Blouin, A. Piris, M.C. Mihm, G. Kaya
Journal: British Journal of Dermatology (2014)

Journal Article Multiple mantleomas: an unusual clinical presentation of an intriguing tumour Get access A.‐M. Thielen, A.‐M. Thielen Department of Dermatology University Hospital of Geneva Geneva Switzerland Search for other works by this author on: Oxford Academic Google Scholar J.‐L. Blouin, J.‐L. Blouin Department of Genetic Medicine and Development University of Geneva Geneva Switzerland Search for other works by this author on: Oxford Academic Google Scholar A. Piris, A. Piris Dermatopathology Unit Harvard Medical School Massachusetts General Hospital Boston MA U.S.A Search for other works by this author on: Oxford Academic Google Scholar M.C. Mihm, M.C. Mihm Department of Dermatology Harvard Medical School Brigham and Women's Hospital Boston MA U.S.A Search for other works by this author on: Oxford Academic Google Scholar G. Kaya G. Kaya Department of Dermatology University Hospital of Geneva Geneva Switzerland Correspondence: G. Kaya. E‐mail: gkaya@hcuge.ch Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 2, 1 August 2014, Pages 417–418, https://doi.org/10.1111/bjd.12924 Published: 01 August 2014
The number needed to treat (NNT) as a measure of drug efficacy: the case of zoledronic acid for early hormone-responsive breast cancer in the ABCSG-12 trial.
Authors: M Gnant, B Mlineritsch, W Schippinger, G Luschin-Ebengreuth, G Steger, V Bjelic-Radisic, R Jakesz, E Kubista, C Marth, R Greil
Journal: Cancer Research (2009)

Abstract Abstract #2113 Background: Zoledronic acid (ZOL) has demonstrated antitumor and antimetastatic activities in preclinical and early clinical studies in many cancer types. The Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12) examined the efficacy of adjuvant therapy in premenopausal women with hormone-responsive early breast cancer receiving goserelin (GOS) + anastrozole (ANA) or tamoxifen (TAM), both ± ZOL. In this trial, ZOL significantly prolonged disease-free survival (DFS) and recurrence-free survival (RFS) versus no ZOL. However, in addition to relative risk reduction, the potential for patients to benefit from a treatment is an important consideration. The number needed to treat (NNT) represents an estimation of the number of patients that have to be treated with an investigational drug for 1 patient to receive clinical benefit within a specific follow-up period. NNT is a powerful, clinically relevant measure of efficacy that can provide a real-world perspective on the efficacy results from clinical trials. Methods: 1,803 patients were randomized to GOS (3.6 mg/28 d SC) + TAM (20 mg/d PO) ± ZOL (4 mg/ 6 mos IV) or GOS + ANA (1 mg/d PO) ± ZOL for 3y. Endpoints at 60 mos for TAM vs ANA and ZOL vs no ZOL were DFS (primary), RFS, overall survival and safety. NNT was calculated for ZOL with respect to DFS and RFS, and compared with other paradigm-changing cancer therapies. Results: After 60 mos median follow-up, ZOL significantly reduced the risk of DFS events by 36% (P = .01) and RFS events by 35% (P = .02) vs no ZOL. For ZOL therapy, NNT = 31 and NNT = 33 to prevent 1 DFS or 1 RFS event respectively at a median follow-up of 60 months. In comparison, the NNT with respect to DFS is 28 for paclitaxel (60-69 months follow-up) and 31 for docetaxel (43-60 months follow-up). Moreover, ZOL was generally well tolerated, and neither ONJ nor renal toxicity was an issue in this setting. Conclusions: The NNT is a simple and effective method to assess clinical trial results that will have relevance to daily practice. In the current comparisons, the NNT for ZOL plus endocrine therapy in ABCSG-12 was similar to the NNTs for taxanes. Therefore the addition of ZOL provides DFS and RFS benefits of magnitudes similar to those from practice-changing chemotherapies like taxanes. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2113.
The rise and fall of Viagra
Authors: A. Berger
Journal: BMJ (1998)

See p 759,760, 765

It must surely be every drug company's dream: to have a product so sexy that the need for marketing and public relations has been obviated by a tidal wave of media hype. Since March 1998, when the little blue pills became available in the United States, we have had news stories, regular updates, features, television and radio programmes, and even serious broadsheet editorials on the myths and legends of what has been dubbed the “Pfizer riser.”

Sadly for Pfizer, however, this very hype may be their undoing. The predicted demand for Viagra (sildenafil), and the consequences this demand is expected to have for the national drug budget, has caused the British government to ban its prescription on the NHS, at least for the time being (p 765).

However, it is better to have realised that this drug has critical implications and delay it now (albeit somewhat late in the day considering how long the man in the street has known about Viagra), than blushingly use the retrospectoscope when all hope of control—legal or otherwise—has long gone.

The debate about who should eventually be able to prescribe sildenafil continues to rage. Most general practitioners I know are rather hoping it will become a drug to be prescribed by …
Myotonia Atrophica and Cyanosis
Authors: Fouad Bashour, Paul Winchell, James Reddington
Journal: New England Journal of Medicine (1955)

IN 1909, Steinert described a familial, chronic, slowly progressive disease characterized by visual and glandular disturbances combined with muscular atrophy. This has been called myotonia atrophica, or Steinert's disease, in contradistinction to myotonia congenita, or Thomsen's disease. Recently, a man with Steinert's disease presented, in addition to the usual findings, marked cyanosis. Physiologic studies were done in an attempt to define the cause of the cyanosis.Case ReportA 57-year-old man was admitted to the hospital complaining of inability to walk for the past 6 years. The illness began at the age of 25, when he noted progressively severe muscular . . .
Characteristics of Glycemic Stability
Authors: F John Service, Roger L Nelson
Journal: Diabetes Care (1980)

Glucose homeostasis in healthy subjects is characterized by postmeal glucose increases of about 40 mg/dl, peaks at about 45 min, decreases close to antecibal levels 1 h after the peak, and no spontaneous oscillations until the next meal. Diabetes is characterized by progressive loss of glucose homeostasis from stable to unstable, which is directly proportional to loss of insulin secretory reserve. Degree of instability of diabetes in ambulatory subjects within a 24-h period can be expressed as mean amplitude of glycemic excursion of M-value and between two successive 24-h periods as mean of daily differences of blood glucose. Stable diabetic persons have lower values, which are closest to those of nondiabetic persons, and unstable diabetic persons have higher values. The mean diurnal blood glucose level is a measure of glycemic control. The failure to restore glycemic patterns of diabetic to those of nondiabetic persons is largely due to the failure of subcutaneously administered insulin to mimic the pattern of insulinemia of healthy subjects.
Management of Patients with Urinary Calculi
Authors: S. J. A. Powis, J. Black, J. A. Macdougall, J. W. Clews
Journal: BMJ (1974)

A retrospective survey was made of 305 patients with proved urinary calculi. When those patients with a solitary stone were compared with those with multiple stones no diagnostically helpful difference was noted in the prevalence of abnormal serum or urine biochemistry, urinary infection, or anatomical abnormality of the urinary tract. The same was true of the stone composition and the need for surgery. It seems that neither routine radiological examination nor regular follow-up is likely to help identify patients whose stones are going to recur.
Impact of Late Drug-Eluting Stent Malapposition on 3-Year Clinical Events
Authors: Myeong-Ki Hong, Gary S. Mintz, Cheol Whan Lee, Duk-Woo Park, Seung-Whan Lee, Young-Hak Kim, Duk-Hyun Kang, Sang-Sig Cheong, Jae-Kwan Song, Jae-Joong Kim, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2007)
Vibrations of Low Frequency over the Precordium
Authors: FRANKLIN D. JOHNSTON, DONALD C. OVERY
Journal: Circulation (1951)

A method for taking tracings which represent actual movements of the precordium (displacement curves) or records which show waves proportional to the velocity of movement of the chest wall (velocity curves) is described. The equipment employed is readily available, and the method is easy to use. The displacement curves are nearly identical with cardiograms taken with a good optical setup, and they may have diagnostic value. The velocity curves are more closely related to the functional status of the myocardium. The clinical significance of these tracings, especially the former, is pointed out.
Herbal Medicines Today and the Roots of Modern Pharmacology
Authors: Peter Goldman
Journal: Annals of Internal Medicine (2001)

The transformation of digitalis from a folk medicine, foxglove, to a modern drug, digoxin, illustrates principles of modern pharmacology that have helped make drugs safer and more effective. Digitalis was improved because its preparation was standardized, first by bioassay and then by chemical methods; however, few of today's herbs are standardized by methods that can ensure a consistent product and, hence, consistent safety and efficacy profiles. Many herbs have been evaluated in randomized, controlled trials, and several-St. John's wort and ginkgo, for example-are apparently effective. Yet, many trials of herbs have limited value because of poor design, small samples, and, above all, use of products of uncertain composition and consistency. The uncertain composition of many herbal products raises questions about their safety, as does evidence indicating that herbs may have harmful interactions with prescription drugs. Such adverse effects of herbs are probably underreported. Meanwhile, systematic studies, such as those identifying adverse reactions to drugs, are hindered because herbal preparations are not standardized-one brand of St. John's wort, for example, will differ chemically from another-and, unlike for prescription drugs, there are no databases linking herb consumption to later medical problems. Since herbal medicines are regulated as dietary supplements, they are not subject to the premarketing regulatory clearance required for drugs. The burden of proof is on the U.S. Food and Drug Administration to show a dietary supplement is unsafe, unlike for drugs, which cannot be approved until the manufacturer has demonstrated safety and effectiveness.
Conditioned medium from keloid keratinocyte/keloid fibroblast coculture induces contraction of fibroblast-populated collagen lattices
Authors: A. Mukhopadhyay, E.K.J. Tan, Y.T.A. Khoo, S.Y. Chan, I.J. Lim, T.T. Phan
Journal: British Journal of Dermatology (2005)

Background Keloid scars represent a pathological response to cutaneous injury. Overproliferation of fibroblasts and overproduction of collagen characterize these abnormal scars. The pathology of these scars remains poorly understood. The role of epithelial–mesenchymal interactions in keloid pathogenesis and scar contracture has recently been explored. Objectives To test our hypothesis that epithelial–mesenchymal interactions play a major role in modulating keloid scar contracture. Methods A coculture model was employed wherein keloid and normal keratinocytes were cocultured with keloid or normal fibroblasts, and the conditioned media from day 5 cocultures were collected to study the effect of the paracrine secretions on contraction of an in vitro fibroblast-populated collagen lattice (FPCL) model. Results Keloid keratinocyte/keloid fibroblast coculture conditioned media brought about increased contraction of the collagen lattice compared with non-cocultured conditioned media. When keloid fibroblasts populated the collagen lattice, significantly increased lattice contraction was induced compared with lattices populated by normal fibroblasts. The addition of antitransforming growth factor (TGF)-β neutralizing antibody to the conditioned media produced an attenuation of the contraction of the FPCLs. When keloid and normal fibroblasts were cultured on chamber slides and treated with conditioned media from coculture and non-coculture series, immunohistochemical analysis demonstrated an increased expression of α-smooth muscle actin (a marker for fibroblast differentiation into myofibroblasts) in fibroblasts exposed to conditioned media from coculture. Conclusions These data indicate that epithelial–mesenchymal interactions are likely to play a major role in scar contracture and scar pathogenesis, and underscore the role of TGF-β1 as a key player in keloid pathogenesis.
Abstract 2520: CHC promotes tumor growth and angiogenesis through regulation of HIF-1α and VEGF signaling
Authors: Kuo-Hua Tung, Han-Chung Wu
Journal: Cancer Research (2012)

Abstract Pancreatic adenocarcinoma is an aggressive disease with a high mortality rate. Currently, treatment options are limited. In an effort to improve the efficacy of treatments for pancreatic adenocarcinoma, we have newly generated a monoclonal antibody (mAb), Pa65-2, which specifically binds to various cancer cells and tumor blood vessels but not to normal cells. According to immunoaffinity chromatography, LC-MS/MS analysis, co-immunoprecipitation and RNA interference studies, the target protein of Pa65-2 is human clathrin heavy chain (CHC). Knocking down CHC with shRNA reduced tumor cell growth, colony formation and invasion in vitro, and inhibited tumor angiogenesis and growth. One of the key functions of CHC was to bind with the transcription factor subunit HIF-1α, increasing the stability of this protein and facilitating its nuclear translocation, thereby regulating the expression of VEGF. In animal studies using NOD/SCID mice bearing pancreatic cancer xenografts, Pa65-2 and CHC shRNA could each inhibit tumor growth and angiogenesis by regulating HIF-1α and VEGF. Furthermore, the expression of CHC, HIF-1α and VEGF was significantly correlated with tumor stage, suggesting that CHC might be a useful prognostic indicator for cancer. Considered together, our results indicate that CHC interacts with and stabilizes HIF-1α, and plays a role in HIF-1α nuclear localization and HRE promoter binding, leading to an increased production of VEGF. These results suggest that the CHC mAb, Pa65-2, can potentially be used to inhibit tumor angiogenesis and growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2520. doi:1538-7445.AM2012-2520
Acute Side Effects and Complications After Short-Term Preoperative Radiotherapy Combined With Total Mesorectal Excision in Primary Rectal Cancer: Report of a Multicenter Randomized Trial
Authors: C. A.M. Marijnen, E. Kapiteijn, C. J.H. van de Velde, H. Martijn, W. H. Steup, T. Wiggers, E. Klein Kranenbarg, J. W.H. Leer
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Total mesorectal excision (TME) surgery in the treatment of rectal cancer has been shown to result in a reduction in the number of local recurrences in retrospective studies. Reports on improved local control after preoperative, hypofractionated radiotherapy (RT) have led to the introduction of a prospective randomized multicenter trial, in which the effect of TME surgery with or without preoperative RT were evaluated. Any benefit in regard to a reduced local recurrence rate and possible improved survival must be weighed against potential adverse effects in both the short-term and the long-term. The present study was undertaken to assess the acute side effects of short-term, preoperative RT in rectal cancer patients and to study the influence of five doses of 5 Gy on surgical parameters, postoperative morbidity and mortality in patients randomized in the Dutch TME trial. PATIENTS AND METHODS: We analyzed 1,530 Dutch patients entered onto a prospective randomized trial, comparing preoperative RT with five doses of 5 Gy followed by TME surgery with TME surgery alone, of which 1,414 patients were assessable. Toxicity from RT, surgery characteristics, and postoperative complications and mortality were compared. RESULTS: Toxicity during RT hardly occurred. Irradiated patients had 100 mL more blood loss during the operation (P &lt; .001) and showed more perineal complications (P = .008) in cases of abdominoperineal resection. The total number of complications was slightly increased in the irradiated group (P = .008). No difference was observed in postoperative mortality (4.0% v 3.3%) or in the number of reinterventions. CONCLUSION: Preoperative hypofractionated RT is a safe procedure in patients treated with TME surgery, despite a slight increase in complications when compared with TME surgery only.