tbuckley/cabot-search huggingface dataset:
Women Doctors—A Review
Authors: Beulah R Bewley
Journal: Journal of the Royal Society of Medicine (1996)

There have been very marked changes in the number of women doctors who have come into the profession in this country in the past 40 years. They have faced problems because of society's preconceptions of their role as women. I previously reviewed their position in 1975 and 1986, and now take a look at areas where progress has been made, and also note whether there is still inequality and where women have still not achieved their full potential. I shall make some suggestions for improvement.
Altered microRNA expression in mycosis fungoides
Authors: J. Maj, A. Jankowska-Konsur, A. Sadakierska-Chudy, L. Noga, A. Reich
Journal: British Journal of Dermatology (2011)

MicroRNAs are small noncoding RNA molecules involved in the regulation of various physiological and pathological processes. Altered expression of different microRNAs has been observed in both solid tumours and haematological malignancies.To investigate expression of several microRNAs in early and advanced mycosis fungoides (MF).Biopsies were obtained from 43 patients with MF (18 early MF and 25 advanced MF) and 23 healthy volunteers. After microRNA isolation, reverse transcriptase reactions were performed, followed by cDNA amplification. The following microRNAs were analysed: miR-15a, miR-16, miR-155, let-7a, let-7d and let-7f. The relative amount of each microRNA was normalized according to the reference RNU48 level.Among the microRNAs studied, only MiR-155 was found to be slightly overexpressed in MF compared with healthy controls. Early MF showed a higher level of all analysed microRNAs after normalization against RNU48 level. Furthermore, metastatic MF demonstrated lower concentrations of let-7a, let-7d and let-7f when compared with MF limited to the skin. The univariate survival analysis and multivariate Cox's regression model revealed that the level of let-7a expression was an independent prognostic indicator.Altered expression of studied microRNAs and the differences between early and advanced MF may suggest that microRNAs play a significant role in MF pathogenesis. It seems that microRNAs could serve as potential therapeutic targets in the future.
Postmarketing surveillance study of a non-chlorofluorocarbon inhaler
Authors: M G Bamber, C. Paterson, J G Ayres, C D Frost, W F Holmes, D R R Williams, S M Ward
Journal: BMJ (1999)

Editor—The study by Ayres et al may have been selectively designed to promote a product as safe; they endorse it as conforming to unpublished guidelines for postmarketing surveillance studies under safety assessment of marketed medicines.1 Withdrawals from the study are mainly for reasons “not related to safety,” and the withdrawal rate of the product under evaluation is almost three times that of the salbutamol inhaler with conventional propellant.

I have several reservations about the study. Postmarketing surveillance studies initiated by the manufacturer are primarily designed to promote a product to the medical profession and the general public. One incentive for patients to enter such a study is the availability of a prescribed drug without charge. Participating general practitioners receive a generous fee—particularly attractive and effective in medical recruitment to this study since “neither the patient nor doctor had to undertake any procedures related to the study.” Criteria of drug safety in this study relate mainly to hospital admissions and perceived adverse effects.

One basic safety criterion—whether the hydrofluoralkane inhaler is reliable—has been omitted from this study. The manufacturer (3M), which sponsored the study, is certainly aware of the problem of failure of the inhaler caused by the nozzle becoming blocked. My practice prescribed and dispensed 356 hydrofluoralkane inhalers to 66 patients, but four fifths of the patients reported or returned the inhalers as faulty, a problem that was not batch related. I reported this problem elsewhere2 and to the Medicines Control Agency in the United Kingdom and the Federal Drugs Agency in the United States, to both of which I sent representative defective samples.

Although blockage of hydrofluoralkane inhalers can be minimised by washing them regularly, this suggests a low margin of safety for this device. Might conflict of interest and suppression of data have resulted in the BMJ’s pages being used for promotional purposes by 3M?
Early Results of Fenestrated Endovascular Repair of Juxtarenal Aortic Aneurysms in the United Kingdom
Authors: G. Ambler, J.R. Boyle, C. Cousins, P.D. Hayes, T. Metha, T.C. See, K. Varty, A. Winterbottom, D.J. Adam, A.W. Bradbury, M.J. Clarke, R. Jackson, J.D. Rose, A. Sharif, V. Wealleans, R. Williams, L. Wilson, M.G. Wyatt, I. Ahmed, R.E. Bell, T.W. Carrell, P. Gkoutzios, T. Sabharwal, R. Salter, M. Waltham, C. Bicknell, P. Bourke, N. Cheshire, I. Franklin, A. James, M.P. Jenkins, M.R. Tyrrell, C.J. Wilkins, M. Bown, E. Choke, M. McCarthy, R. Sayers, A. Tamberaja, F. Farquharson, F. Serracino-Inglott, M. Davis, G. Hamilton, J.A. Brennan, R. Canavati, R.K. Fisher, R.G. McWilliams, J.B. Naik, S.R. Vallabhaneni, J. Hardman, S. Black, R. Hinchliffe, P. Holt, I.M. Loftus, T. Loosemore, R Morgan, M.M. Thompson, O. Agu, C. Bishop, D. Boardley, J. Cross, J. Hague, P.L. Harris, K. Ivancev, J. Raja, T. Richards, D. Simring, A.C. Fisher, D. Smith, G.P. Copeland
Journal: Circulation (2012)

Fenestrated endovascular repair of abdominal aortic aneurysms has been proposed as an alternative to open surgery for juxtarenal and pararenal abdominal aortic aneurysms. At present, the evidence base for this procedure is predominantly limited to single-center or single-operator series. The aim of this study was to present nationwide early results of fenestrated endovascular repair in the United Kingdom.All patients who underwent fenestrated endovascular repair between January 2007 and December 2010 at experienced institutions in the United Kingdom(>10 procedures) were retrospectively studied by use of the GLOBALSTAR database. Site-reported data relating to patient demographics, aneurysm morphology, procedural details, and outcome were recorded. Data from 318 patients were obtained from 14 centers. Primary procedural success was achieved in 99% (316/318); perioperative mortality was 4.1%, and intraoperative target vessel loss was observed in 5 of 889 target vessels (0.6%). The early reintervention (<30 days) rate was 7% (22/318). There were 11 deaths during follow-up; none were aneurysm-related. Survival by Kaplan-Meier analysis was 94% (SE 0.01), 91% (0.02), and 89% (0.02) at 1, 2, and 3 years, respectively. Freedom from target vessel loss was 93% (0.02), 91% (0.02), and 85% (0.06), and freedom from late secondary intervention (>30 days) was 90% (0.02), 86% (0.03), and 70% (0.08) at 1, 2, and 3 years.In this national sample, fenestrated endovascular repair has been performed with a high degree of technical and clinical success. Late survival and target vessel patency are satisfactory. These results support continued use and evaluation of this technique for juxtarenal aneurysms, but illustrate the need for a more robust evidence base.
Abstract 661: Dual Antiplatelet Therapy And Heparin "Bridging" Significantly Increase The Risk Of Bleeding At Device Implantation
Authors: Christine Tompkins, Alan Cheng, Darshan Dalal, Jeffrey A Brinker, Charles T Leng, Joseph E Marine, Saman Nazarian, David D Spragg, Sunil Sinha, Henry Halperin, Gordon F Tomaselli, Ronald D Berger, Hugh Calkins, Charles A Henrikson
Journal: Circulation (2008)
Evaluation of tumor gene expression and <i>K-Ras</i> mutations in FFPE tumor tissue as predictors of response to cetuximab in metastatic colorectal cancer
Authors: J. B. Baker, D. Dutta, D. Watson, T. Maddala, S. Shak, E. K. Rowinsky, L. Xu, E. Clark, D. J. Mauro, S. Khambata-Ford
Journal: Journal of Clinical Oncology (2008)

3512 Background: The anti-EGFR monoclonal antibody cetuximab shows activity in a subset of patients with metastatic colorectal cancer (mCRC). This study was conducted to discover and validate markers that are found to be associated with disease control and improved progression-free survival (PFS) time in patients treated with cetuximab. Methods: Formalin-fixed paraffin-embedded primary tumors of 226 patients from three studies of cetuximab monotherapy in advanced mCRC were retrospectively assayed for K-Ras mutations and for expression of candidate genes. The expression of K-Ras sequences (7 mutations and 1 wild-type) and 102 candidate genes were measured by quantitative RT-PCR. Statistical associations of mutation and gene expression with disease control (CR+PR+SD) or PFS were determined. Results: 82 (36%) of the 226 analyzed samples had K-Ras mutations. Patients whose tumors did not have K- Ras mutations had a significantly higher disease control rate (60%) than those with K-Ras mutations (23%) (p<< 0.001). Among all 226 patients, quantitative expression of 40 genes was significantly associated with disease control (p<0.05) after adjusting for multiplicity. Among 144 patients without K-Ras mutation, 31 genes were significantly associated with disease control (p<0.05) after adjusting for multiplicity. Genes that were strongly associated with disease control in both analyses included genes encoding the EGFR ligands epiregulin (EREG) and amphiregulin (AREG). Based on these results, we have developed multi-gene predictors that incorporate EREG and AREG, which when used in conjunction with K-Ras mutation status increase the ability to predict who might benefit from cetuximab treatment over K-Ras mutation status alone. Conclusions: A multi-parameter marker test comprising of K-Ras mutation status in combination with the expression levels of a small number of genes could be developed further to select patients for cetuximab therapy. Applicability of this test to cetuximab combination therapy should be explored. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Genomic Health, Inc., ImClone Systems, Inc. Bristol-Myers Squibb, Genomic Health, Inc., ImClone Systems, Inc.
A phase III randomized study comparing the effects of oxandrolone (Ox) and megestrol acetate (Meg) on lean body mass (LBM), weight (wt) and quality of life (QOL) in patients with solid tumors and weight loss receiving chemotherapy
Authors: G. J. Lesser, D. Case, F. Ottery, R. McQuellon, J. K. Choksi, G. Sanders, R. Rosdhal, E. G. Shaw
Journal: Journal of Clinical Oncology (2008)

9513 Background: Involuntary wt loss is a significant problem in patients (pts) with cancer which disproportionately represents a loss of muscle mass. Ox is a potent oral anabolic steroid exhibiting minimal androgenic effects which promotes wt gain primarily through an increase in LBM. Methods: We performed a prospective, randomized phase 3 trial comparing the effects of Ox (10mg bid) and MA (800mg qd) on wt, body composition and QOL in adult pts with solid tumors and wt loss receiving chemotherapy. Body composition was serially assessed by Bioelectrical Impedance Analysis. The impact of these agents on QOL was evaluated using the FACT-G and the Anorexia/Cachexia subscale. The primary outcome was LBM after 12 weeks of drug therapy. Secondary outcomes included wt, fat mass, and QOL. Linear mixed effects models were used to assess the effect of treatment on these outcomes over time. Results: 155 pts were randomized and the study has been completed. Baseline demographics: median age 64 years; 41% female; 63% stage 4; performance status 0/1/2=8%/61%/31%; even distribution between study arms. At 12 weeks, significant changes from baseline were observed for wt (lbs) (Ox −3.4 vs MA +5.8, p<.001) and fat mass (Ox −4.89 vs MA +2.68, p<.001). An increase in LBM (lbs) (Ox 2.7 vs MA 0.8; p=.11) was observed but did not reach statistical significance. Neither treatment impacted global QOL or fatigue, but both showed improvement on the subscale (Ox 6.7 vs MA 11.3; p=.01). Eleven serious adverse events (Ox 4, MA 7) were attributed as at least possibly related to study drug. Only 50% of pts (Ox 39%, MA 63%) remained on study at 12 weeks; a dropout rate consistent with similar palliative care trials. Conclusions: Pts treated with Ox still lost wt but experienced an increase in LBM, a reduction in fat mass and reduced self-reported anorectic symptoms. MA therapy was associated with an increase in weight and fat mass, minimal change in LBM and improved appetite. The complementary effects of the two agents on appetite, overall wt gain and LBM suggest that their combination may result in optimal effects in a similar pt population. Supported by NCI grant 1 U10 CA8185 and Savient Pharmaceuticals, Inc. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Savient Pharmaceuticals Savient Pharmaceuticals
Abstract 5495: Role of SIRT1 in Smooth Muscle Cell Function and Vascular Remodeling
Authors: Daniel Sedding, Sabina Vogel, Harald Tillmanns
Journal: Circulation (2008)

Background: The class III histone deacetylase SIRT1 has been identified as a key regulator of ageing and longevity in model organisms such as S. cerevisiae and C. elegans, which regulates cellular functions such as differentiation, senescence and metabolism. However, the role of SIRT1 for Smooth muscle cell (VSMC) function and vascular homeostasis or during vascular remodelling remains unknown. Methods and Results: Here, we show that SIRT1 is highly expressed in intact blood vessels in vivo as well as in cultured VSMC. Stimulation of SIRT1 activity by either treatment with the SIRT1 activator resveratrol or adenoviral overexpression of wild type SIRT1 but not with an inactive SIRT1 mutant attenuated serum-induced VSMC proliferation in a dose dependent manner in vitro. In contrast, treatment of VSMC with the small molecule weight inhibitors of SIRT1, nicotinamide and sirtinol, augmented the proliferative and migratory activity of VSMC. Consistent with these data, MEF cells isolated from SIRT −/− mice showed an augmented proliferative response to serum stimulation but were also more resistant to starving-induced apoptosis compared to WT-MEF cells. Silencing of endogenous SIRT1 using siRNA resulted in an increased proliferation, migration and apoptosis of VSMC. In vivo, following arterial injury of the mouse femoral artery, SIRT1 was downregulated in the developing neointima. Adenoviral-mediated reconstitution of wild type SIRT1 but not of the inactive SIRT1 mutant prevented neointima formation in vivo. Conclusion: Thus, these data identify SIRT1 as a key regulator of vascular proliferative disease processes and indicate that SIRT1 plays an essential role in proliferative migratory and apoptotic processes which regulate vascular homeostasis and remodeling.
Proapoptotic Function of Integrin β3 in Human Hepatocellular Carcinoma Cells
Authors: Yanhua Wu, Jie Zuo, Guoqing Ji, Hexige Saiyin, Xing Liu, Feiyu Yin, Ning Cao, Yunfei Wen, Jian Jian Li, Long Yu
Journal: Clinical Cancer Research (2008)

Abstract Purpose: This study evaluates the proapoptotic function of integrin β3 in human hepatocellular carcinoma (HCC). Experimental Design: The expression of integrin β3 in 67 HCC specimens paired with corresponding neighboring nontumorous tissue was studied by quantitative real-time PCR and Western blot. The proapoptotic function of integrin β3 in SMMC-7721 human hepatoma cells overexpressing ITGB3 (gene coding integrin β3) was determined through colony formation, serum starvation, and anoikis assay. Results: Compared with neighboring pathologically normal liver tissue, ∼60% of the HCC specimens showed a significant down-regulated level of integrin β3 expression. Transient expression of integrin β3 in SMMC-7721 resulted in an enhanced level of apoptosis and suppression of colony formation. Cell growth inhibition on serum/ligand deprivation and incidences of anoikis were remarkably increased in SMMC-7721 with stable expression of integrin β3 in comparison with vector control transfectants. In addition, expression of fibrinogen and vitronectin, two native ligands for integrin αvβ3 in liver, was inhibited, which was correlated with the decreased integrin β3 expression. Replenishing these ligands to the starved SMMC-7721 stable transfectants effectively restored the proapoptotic function of integrin β3. Conclusions: Down-regulation of integrin β3 and its ligands in liver is related to the aggressive growth of HCC. Thus, reconstitution of integrin β3 in HCC may be a potential therapeutic approach to inhibit aggressive growth of liver cancer.
Retrospective review of DPACE therapy for aggressive, refractory multiple myeloma (MM)
Authors: A. S. Gerrie, W. Xu, S. Fung, A. K. Stewart, D. Reece, S. Trudel, J. Mikhael, C. I. Chen
Journal: Journal of Clinical Oncology (2007)

18500 Background: Oral dexamethasone ± thalidomide with a 4-day infusion of cisplatin, doxorubicin, cyclophosphamide, and etoposide (DPACE) is an effective induction therapy prior to transplant in patients (pts) with MM. Limited experience also suggests DPACE may reduce disease burden as a salvage regimen for aggressive, refractory MM. Methods: We performed a retrospective review from 1999- 2005 of all MM pts who received DPACE ± thalidomide as a salvage regimen at our center. Results: A total of 39 pts received DPACE at a median 23 mos from diagnosis (range, 10–84). Median age was 53 years (34–70), 51% stage 3 at diagnosis. Plasma cell leukemia had developed in 12 pts and leptomeningeal disease in 4 pts at time of DPACE. Ten of 24 pts (42%) with cytogenetics had del 13q. Pts were heavily pretreated (median 3 prior regimens; prior autotransplant [ASCT] 38%; thalidomide 64%; and bortezomib 10%). Pts received 1–4 cycles as tolerated for refractory (83%) or relapsed (17%) disease. Thalidomide was used in 41% of cycles. Hematologic toxicity was common (grade 3–4 neutropenia 92% and thrombocytopenia 72%). Although G-CSF was used in 71% of cycles, febrile neutropenia was common (53%) and 26% required hospitalization. Overall RR was 36% (14 pts: PR 12, VGPR 2). An additional 8% achieved MR, 23% SD. PD occurred in 15% and 18% died on therapy (4 progressive MM; 2 neutropenic sepsis, 1 GI bleed). No prior ASCT (p=0.04) and &lt;4 prior regimens (p=0.04) predicted for response to DPACE. Eleven pts proceeded to ASCT and one pt to a clinical trial with lenalidomide with a median OS from DPACE of 24.7 mos (95% CI, 11.2–63.6). Those who did not bridge to transplant or trial (n=27) had a short median PFS of 3.0 months (95% CI, 1.2–5.5) and OS of 6.7 mos (95% CI, 1.8–9.7). OS for all 39 pts was 8.7 mos (95% CI, 6.4–12.4). Conclusion: DPACE may be effective salvage therapy for heavily pretreated MM pts. Although the RR of 36% in this poor prognosis cohort is reasonable, the PFS is short and suggests that the best role for this regimen is in bridging to more definitive therapy such as transplantation. [Table: see text]
Electrically-activated dilator muscles reduce pharyngeal resistance in anaesthetized dogs with upper airway obstruction
Authors: H Bishara, M Odeh, RP Schnall, N Gavriely, A Oliven
Journal: European Respiratory Journal (1995)

There is current controversy as to whether electrical stimulation of upper airway musculature can be used us a beneficial treatment modality in patients with obstructive sleep apnoea syndrome. Increased upper airway (UAW) muscle activity decreases UAW resistance (Ruaw) in isolated UAW of dogs. In the present study, we evaluated the effect of UAW muscle contraction on UAW patency in anaesthetized dogs in vivo breathing spontaneously through partially and completely obstructed UAW. Airflow and supraglottic pressure were measured to obtain Ruaw. Ruaw could be regulated by inhalation of a rubber balloon implanted transcutaneously in the pharyngeal submucosa to produce partial or complete obstruction. Wire electrodes were implanted bilaterally into the genioglossus (GG), geniohyoid (GH), sternothyroid (ST), and sternohyoid (SH) muscles for electrical stimulation (ES), and into the alae nasi for electromyographic (EMG) recording. Three levels of electrical stimulation were delivered to each muscle before and during partial or complete UAW obstruction. Genioglossus and geniohyoid stimulation both resulted in a significant reduction in Ruaw, which was most pronounced during partial obstruction, reducing Ruaw from 54 +/- 11 to 14 +/- 3 and from 74 +/- 12 to 31 +/- 5 cmH2O.L-1.s, respectively. At low voltage, stimulation of the genioglossus was more effective than stimulation of the geniohyoid in reducing Ruaw. Furthermore, electrical stimulation of the genioglossus but not of the geniohyoid released total obstruction. In contrast, electrical stimulation of the sternohyoid and sternothyroid produced no significant change in Ruaw. These findings demonstrate that selective UAW dilatory muscle contraction in spontaneously breathing anaesthetized dogs reduces Ruaw in the presence of UAW obstruction and releases UAW occlusion, with the genioglossus being the most effective muscle. This favours further attempts to investigate the benefits of electrical stimulation of selected upper airway muscles in the treatment of obstructive sleep apnoea syndrome.
Persistent fever in pulmonary tuberculosis
Authors: J. Crofton, P D O Davies
Journal: BMJ (1997)

Introducing the postoperative care team Effective postoperative care remains surgeons' roleEditor-I am concerned that the suggestions made by David R Goldhill might be taken too seriously rather than remain a point for discussion. 1 Goldhill is right in his assertion that patients can fare badly in their postoperative course because of lack of attention by their attendants and lack of understanding of common postoperative complications.I believe, however, that he has missed the opportunity to lay the blame at the correct door.Surely it is the surgeons' role to carry out preoperative assessment, surgery, and effective postoperative care.If they choose to emphasise their importance in the operating theatre, delegating their other responsibilities to their trainees, the nurse practitioners, and the anaesthetists, why should we encourage this path?Undoubtedly, anaesthetists are fast becoming the new generalists, with an increasing role outside the operating theatre.These new skills and responsibilities include pain control, intensive care, and transoesophageal echocardiography, to name but a few.Some of my professional colleagues may relish even more diversification and abhor my comments.Goldhill implies that anaesthetists and postoperative care nurses will lead the postoperative care team; indeed, this is already happening in North America, where they have been sent to run preoperative assessment clinics by surgeons based in the operating room.If the surgical ward round in your hospital has become a quick look through the laboratory results and a glance at the chest radiograph before a rush to the changing rooms then I suggest that waiting for the confidential inquiry into perioperative deaths to point out the obvious is not the solution.