tbuckley/cabot-search huggingface dataset:
Total Hip Replacement in Inflammatory Hip Disease using the Charnley Prosthesis
Authors: J. Harris, C. D. R. Lightowler, R. C. Todd
Journal: BMJ (1972)

The Charnley low-friction arthroplasty was performed on 73 hips in 55 patients with inflammatory joint disease, usually for intolerable pain. Sixty-five of these operations were reviewed at a special clinic or by postal questionnaire; 57 hips were painfree or gave rise to only occasional discomfort, in 58 there was an increased range of movement, and in 46 of the 59 hips assessed clinically, the results were excellent or good. The most serious complication was deep infection, which occurred in 7 operations.
Phase 1 dose-escalation study of IV ixazomib, an investigational proteasome inhibitor, in patients with relapsed/refractory lymphoma
Authors: S E Assouline, J Chang, B D Cheson, R Rifkin, S Hamburg, R Reyes, A-M Hui, J Yu, N Gupta, A Di Bacco, Y Shou, P Martin
Journal: Blood Cancer Journal (2014)

Ixazomib is an investigational proteasome inhibitor that has shown preclinical activity in lymphoma models. This phase 1 study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics and preliminary activity of intravenous (IV) ixazomib in relapsed/refractory lymphoma patients who had received ⩾2 prior therapies. Thirty patients with a range of histologies received ixazomib 0.125−3.11 mg/m2 on days 1, 8 and 15 of 28-day cycles. Patients received a median of two cycles (range 1−36). MTD was determined to be 2.34 mg/m2. Most common drug-related adverse events (AEs) included fatigue (43%), diarrhea (33%), nausea, vomiting and thrombocytopenia (each 27%). Drug-related grade ⩾3 AEs included neutropenia (20%), thrombocytopenia (13%) and diarrhea (10%). Drug-related peripheral neuropathy occurred in four (13%) patients; no grade ⩾3 events were reported. Plasma exposure increased dose proportionally from 0.5−3.11 mg/m2; terminal half-life was 4−12 days after multiple dosing. Of 26 evaluable patients, five achieved responses: 4/11 follicular lymphoma patients (one complete and three partial responses) and 1/4 peripheral T-cell lymphoma patients (partial response). Sustained responses were observed with ⩾32 cycles of treatment in two heavily pretreated follicular lymphoma patients. Results suggest weekly IV ixazomib is generally well tolerated and may be clinically active in relapsed/refractory lymphoma.
A 40-Year-Old Woman With a Strong Family History of Breast Cancer
Authors: Judy Garber
Journal: JAMA (1999)

DR DALEY: Mrs T is a 40-year-old married mother of 3 children with a strong family history of breast cancer who is considering genetic testing and tamoxifen therapy. She lives on Cape Cod, Mass, and works at home caring for her 3 children, ages 7, 5, and 2. Her health insurance is provided through a managed care plan. Mrs T is in good health. She is of Dutch and English ancestry. Her maternal grandmother was diagnosed with breast cancer in her seventh decade and was treated with surgery. She died of causes unrelated to breast cancer. Mrs T’s mother developed breast cancer and died of complications related to breast cancer metastatic to bone. Her sister developed breast cancer at age 26 and died at age 38 of complications related to metastatic breast cancer to lymphatics and lung. Mrs T has had yearly mammography since age 23 and semiannual breast examinations. She practices breast selfexamination. Mrs T has decided not to have genetic testing because she is aware that negative test results do not assure her that she will not develop breast cancer. She says that having a prophylactic mastectomy would be a “big” decision. After several months of consideration, she recently began a course of tamoxifen and has not experienced any noticeable adverse effects. She is ambivalent about genetic testing, wants to know what the future of “gene therapy” is, and is curious about what the future holds for her 2-yearold daughter. Her past medical history is not significant. She drinks socially and smokes about one-half pack of cigarettes daily. Her only current medication is tamoxifen. Physical examination in the fall of 1998 revealed a thin woman in no acute distress. General physical examination findings were normal. Breast examination findings were normal without palpable masses and no axillary masses. Mammogram was negative for masses or calcifications.
Influence of experimental diabetes on the mechanical responses of canine coronary arteries: role of endothelium
Authors: D. GEBREMEDHIN, M. Z. KOLTAI, G. POGATSA, K. MAGYAR, P. HADHAZY
Journal: Cardiovascular Research (1988)

The influence of experimental diabetes on the endothelium mediated relaxation and contractile responses of canine isolated coronary arteries was studied in arteries removed from alloxan treated diabetic (280 mmol.kg-1) and control mongrel dogs. Strips with and without endothelium were suspended in Krebs bicarbonate solution for isometric recording. Relaxation responses to acetylcholine (1.8 X 10(-8) to 9.4 X 10(-6) mol.litre-1, A23187 (10(-8) to 1.28 X 10(-6) mol.litre-1), and sodium nitroprusside (10(-9) to 10(-7) mol.litre-1) as well as contractile responses to prostaglandin F2 alpha, (1.7 X 10(-7) to 5.6 X 10(-4) mol.litre-1) were determined. In all intact strips acetylcholine, and A23187 induced similar concentration dependent reduction of the prostaglandin F2 alpha (2 X 10(-6) mol.litre-1) evoked tone. No significant difference was observed between sodium nitroprusside evoked relaxations of normal and diabetic arteries. Cyclooxygenase blockade reduced the maximal relaxations induced by acetylcholine and A23187 in diabetic vessels, whereas it did not change the endothelium dependent relaxation of normal arteries. Diabetes increased significantly the sensitivity to acetylcholine (EC50 4.1(0.4) X 10(-7) mol.litre-1 in control and 6(0.7) X 10(-8) mol.litre-1 in diabetic arteries; p less than 0.01, n = 7) and to A23187 (EC50: 7(1) X 10(-8) mol.litre-1 in control and 3.8(0.3) X 10(-8) mol.litre-1 in diabetic vessels; p less than 0.01, n = 7); in contrast, prostaglandin F2 alpha remained an equiactive constrictor in normal and diabetic vessels with intact endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
Dendritic cells in liver injury and fibrosis: Shortcomings and promises
Authors: Veronika Lukacs-Kornek, Detlef Schuppan
Journal: Journal of Hepatology (2013)

The phenotype and function of liver dendritic cells (LDCs) are poorly understood. This Snapshot summarizes our current knowledge on LDCs in the healthy and injured liver, and their role in fibrosis progression and reversal. It also draws attention to various pitfalls in the current experimental design and conclusions based on available data.
Dose-Related Efficacy of Levomethadyl Acetate for Treatment of Opioid Dependence
Authors: Thomas Eissenberg
Journal: JAMA (1997)

<h3>Objective.</h3> —To compare the clinical efficacy of different doses of levomethadyl acetate hydrochloride (known as LAAM) in the treatment of opioid dependence. <h3>Design.</h3> —A randomized controlled, double-blind, parallel group, 17-week study. <h3>Setting.</h3> —Outpatient facilities at Johns Hopkins University Bayview Medical Center, Baltimore, Md. <h3>Patients.</h3> —Opioid-dependent volunteers (N=180) applying to a treatment-research clinic. <h3>Intervention.</h3> —Thrice-weekly (Monday/Wednesday/Friday) oral LAAM dose conditions of 25/25/35 mg, 50/50/70 mg, and 100/100/140 mg and nonmandatory counseling. <h3>Main Outcome Measures.</h3> —Retention in treatment, self-reported heroin use, and opioid-positive urine specimens. <h3>Results.</h3> —Retention was independent of subjects' sex and dose. Self-reported heroin use decreased in a dose-related manner. At final assessment, patients in the high-dose condition reported using heroin 2.5 of 30 days as compared with 4.1 or 6.3 days for patients in the medium-dose and low-dose conditions, respectively (high dose vs low dose,<i>P</i>&lt;.05); urinalysis results were similarly dose related. Overall, 20 (34%) of 59 patients in the high-dose condition remained opioidabstinent for 4 consecutive weeks, as compared with 8 (14%) of 59 in the medium-dose and 7 (11%) of 62 in the low-dose conditions (<i>P</i>&lt;.01). Self-report and urinalysis data are consistent with a greater than 90% reduction in illicit opioid use by the high-dose group relative to pretreatment levels. <h3>Conclusion.</h3> —Opioid substitution treatment with LAAM substantially reduces illicit opioid use. The clinical efficacy of LAAM is positively related to dose.
Legitimate and Ethical: Distinguishing When and How Regulations Apply in Patient-Oriented Research
Authors: Simon J. Craddock Lee, Jasmin A. Tiro, Wendy Pechero Bishop, P. Diane Sheppard, Celette Sugg Skinner
Journal: The American Journal of Bioethics (2011)

Click to increase image sizeClick to decrease image size Acknowledgments Authors acknowledge support from North and Central Texas Clinical & Translational Research Institute (NIH CTSA UL1 RR024982) and the UT Harold C. Simmons Cancer Center (NCI 1P30CA142543-01).
Sir James Crichton-Browne
Authors: G. K York
Journal: Journal of the Royal Society of Medicine (2005)

Jaundice as a presentation of heart failureAs many as 55% of 42 patients with severe congestive cardiac failure (CCF) (characterized by a cardiac index of 1.5 L/ min/m 2 or less) may have raised serum alkaline phosphatase, 1 yielding a prevalence of this liver enzyme derangement twice that documented by van Lingen et al. (September 2005 JRSM 2 ).Accordingly, jaundice and/or serum alkaline phosphatase hotline would be more informative than an exclusively jaundice hotline service for elucidating the distinguishing features (if any) of those patients in whom CCF co-exists with potentially treatable choledocholithiasis.This scenario is especially likely in the elderly, in whom the age-related nature of the two disorders 3,4 makes it increasingly likely that they will co-exist by pure chance; the confusion between the two disorders is compounded when co-prescription of warfarin is complicated either by idiosyncratic warfarin-related cholestasis 5 or by anticoagulant-related haemobilia. 6 I agree that correct evaluation of jugular venous pressure (JVP) is crucial to the differential diagnosis between CCFrelated jaundice and other causes of jaundice.[I would add that the time is long overdue for non-cardiology internists to abandon the so-called 'JVP raised to 2 cm' calibration so widely prevalent in the clerking of CCF patients].However, this is not the whole story.The biochemical stigmata of CCF-related jaundice can be indistinguishable from those of choledocholithiasis, 1 justifying a vigilant awareness of the possibility of the co-existence of the two disorders in every CCF patient in whom serum alkaline phosphatase of hepatic origin is elevated to twice or more of the upper limit of normal, irrespective of the severity of jaundice, and, possibly, even regardless of whether or not the patient is jaundiced. 7
Double-balloon endoscopy
Authors: H. Yamamoto, C. Ell, K. Binmoeller
Journal: Endoscopy (2008)

Double balloon endoscopy (DBE) was developed for the examination of the small intestine. DBE together with capsule endoscopy have improved the endoscopic approach to the small intestine, and revolutionized the management of small-intestinal diseases. DBE features not only deep intubation of the small bowel, but also the improved control of the endoscope tip, even in the distal small intestine. This improved control is provided by stabilization from the overtube balloon. In this article, we explain how to use DBE effectively and safely. The basic principles of DBE are discussed as well as proper techniques, tips for effective insertion of the double balloon endoscope, proper indications of DBE, and endoscopic therapies in the small intestine.
An Address ON THE EXOTIC FLORA OF THE UTERUS IN RELATION TO FIBROIDS AND CANCER: Delivered before the Bradford Medico-Chirurgical Society on the occasion of its Jubilee, January 21st, 1913
Authors: J. Bland-Sutton
Journal: BMJ (1913)

IN the year 1910, at the Middlesex Hospital, the uterus wNas removed for fibroids on 65 occasions, anld all the women recovered.During the same period the utertus was extirpated for cancer of its neck in 17 women, and of tllese 4 died.Tlle annual report for that year slhows that 13 patients witlh cancer of the cervix uteri were examined under an anaesthetic and found to be " inoper- able."In 5 more women with the same disease the condition of the pelvic organs was examiiined tlhrouiglh an incision in tlle abdominal wall, and proved to be unsuitable for hlysterectomy.'Tlius, ouit of 35 women with this terrible disease 17 were selected with extreme care as suitable for hysterectomy, and of tllese 4 died from-l the operation or its sequelae.Although these facts are taken fromii tlle reports of one liospital, the results are by lno means peculiar to it.An examination of the reports of some other hospitals in London reveals practically the same picture.In the year 1910 abdominal hysterectomny was performed for fibroids in seven hospitals in London on 370 patients with 9 dleatlhs: Middlesex Chelsea (for Women) Samaritan (for Wcmen) New (for Women)... UIIiversity .. St. Thomas's ... St. Bartholomew's Cases.Deatls.65 0 113 2 53 3 41 1 14 0 50 .3 34
Long term management of patients after splenectomy.
Authors: M McMullin, G Johnston
Journal: BMJ (1993)

tamoxifen in younger women (aged 35) in some preventive trials.Information from epidemiological and laboratory studies suggests that the breast tissue is most receptive to carcinogens early in puberty 1516 and antihormonal prevention is most effective nearer the time of the insult.'7This is why young women are being recruited.Only young women at the highest risk of developing breast cancer, however, are being included in the prevention studies.Carefully monitored adjuvant clinical trials can guide the use of tamoxifen in normal women.The physiological impact of tamoxifen in premenopausal women warrants closer attention; the drug's effects on bone density and lipid concentrations might tip the balance of risks and benefits in its favour.
Anabolic-androgenic steroid use among young male and female athletes: is the game to blame?: Table 1
Authors: P A Harmer
Journal: British Journal of Sports Medicine (2009)

The use of anabolic-androgenic steroids (AAS) by young athletes has been a primary concern of sports governing bodies because of the implications for unfair advantage in performance and the potential for adverse side effects. Research over several decades indicated a lifetime prevalence of AAS use for adolescent males of 4–6% and for females of 1.5–3%, indicating a problem involving millions of athletes and a potential epidemic of AAS-related pathologies. However, recent studies have questioned the presumption that participation in organised sport is the primary risk factor for AAS use in adolescents as well as the extant estimates of the magnitude of the problem. Increasing evidence indicates that AAS use is associated with non-athletes and is linked to a broader syndrome of problem behaviours rather than efforts to achieve sporting success, and that sports participation may be protective against AAS use. Moreover, employing lifetime prevalence to gauge AAS use limits accurate evaluation of the personal and public health risk as the majority of respondents are not habitual users. Previous studies may have also inflated prevalence values through ambiguously worded survey questions and other design flaws, and few data are available on actual dosages. Prevention efforts need to be focused beyond organised sport and target the general adolescent population rather than athletes and should be founded on interventions with demonstrated efficacy for delinquent, antisocial and self-destructive behaviours rather than the ethical imperative of fair play.
Making measurements in the pulmonary circulation: when and how?
Authors: D. Raeside, A. Peacock
Journal: Thorax (1997)

Primary pulmonary hypertension is a well known though in patients with persistent hypoxaemia (Pa2 <7.3 kPa) who complain of deteriorating exercise tolerance in the rare condition, but pulmonary hypertension also occurs as a consequence of most heart and lung diseases where it is face of static spirometric values, or in those who develop evidence of fluid retention. This can be a difficult clinical largely unrecognised and untreated and is therefore a major clinical challenge. The consequence of this failure to assess diagnosis and one American study noted that up to 30% of admissions to hospital with a diagnosis of congestive the pulmonary circulation is that the process may progress to the point where treatment is less likely to be beneficial. cardiac failure actually had fluid retention associated with pulmonary hypertension. It is because the symptoms and signs of pulmonary hypertension are often rather vague and non-specific that it There is little doubt that secondary pulmonary hypertension is an important factor in the morbidity and is important to be aware of methods of measurement in the pulmonary circulation and their sensitivity, specificity, mortality of chronic hypoxic lung disease and other conditions. Quantifying pulmonary haemodynamics should be and relative merits. There is no easily applied sphygmomanometer for the pulmonary circulation, but there are a an important part of assessment of these patients and can assist us in future decisions about the success or otherwise number of techniques – both invasive and non-invasive – which can help us to make the diagnosis. Implicit in the of treatment directed both at the primary respiratory disease and at the pulmonary circulation itself. Clearly, the first desire to make an earlier diagnosis of pulmonary hypertension is the belief that there is some point in doing therapeutic objective must be the treatment of the pulmonary condition, but we should be monitoring the effects so – that is, that the condition is itself of significance and that we may be able to offer some additional treatment to of this treatment and the use of vasodilators, if appropriate, on the pulmonary circulation. the patient.
Polyacrylate nanoparticles: toxicity or new nanomedicine?
Authors: H. Ren, X. Huang
Journal: European Respiratory Journal (2010)

as demonstrated in the Understanding Potential Long-Term Improvements in Function with Tiotropium (UPLIFT1) trial [4].The authors are correct in highlighting the notable differences between the Lung Health Study and UPLIFT1 study populations with respect to age and disease severity.It is of interest, however, that, in the Lung Health Study, a post hoc subanalysis of the annual rates of decline by smoking category (continuing smokers, intermittent smokers and sustained quitters), baseline lung function (range 90-55% predicted FEV1) and age (range 35-70 yrs) showed that baseline disease severity (FEV1 % predicted) was not predictive of the annual change in FEV1 in mL?yr -1 within any smoking category, whereas older subjects who were either continuing or intermittent smokers had a slightly more rapid annual decline in lung function than younger subjects in the same smoking categories, although among quitters age did not influence FEV1 decline [2].These findings suggested that smoking cessation leads to generally comparable benefits (in terms of slowing disease progression) across the spectrum of middle to older age and mild to moderate disease severity.The UPLIFT1 trial results appear to confirm and extend the findings from the Lung Health Study to an older and more severely diseased COPD population.J. Zielinski and co-workers suggest that the UPLIFT1 data be formally analysed further to compare the rates of decline among the three smoking categories.Unfortunately, such a subgroup analysis would be problematic, since the three subgroups are defined by post-randomisation smoking status and are not comparable with respect to such baseline variables as age, Global Initial for Chronic Obstructive Lung Disease stage, FEV1 % predicted and sex [4].
Language of Medical Care
Authors: Richard M. Magraw
Journal: New England Journal of Medicine (1968)

Wittgenstein's idea that "analysis is the battle against the bewitchment of our intelligence by language" has particular relevance in debates about medical care. Metaphors and oratorical devices used at first for effect have slipped into common parlance, and distortions embedded in this new jargon now muddy our thinking.Consider the relatively innocuous phrase "health care" used as a condensation of the longer "medical care and health services." Patients are "cared for," sickness is "cared for." Is health "cared for," or is it better "maintained"? Care can mean either nurture and repair or maintenance, but, in the medical context, it usually . . .
Abstract 4492: Structure-activity relationship study anti-microtubule agents targeting the colchicine site on tubulin that circumvent drug resistance.
Authors: Aleem Gangjee, Weiguo Xiang, Susan L. Mooberry, Ernest Hamel
Journal: Cancer Research (2013)

Abstract The vinca alkaloids and taxanes are successful antitumor agents. However, drug resistance limits their clinical utility in cancer chemotherapy. Overexpression of P-glycoprotein (Pgp) and expression of the β-tubulin subtype, β-III tubulin, are two clinically established drug resistance mechanisms that reduce the effectiveness of these agents. In 2010, we reported that the 6-CH3 cyclopenta[d]pyrimidine scaffold affords water soluble antimitotic agents targeting the colchicine site on tubulin. Molecular modeling and docking studies of the parent compound in the X-ray crystal structure of tubulin (PDB: 1SA0) suggested that the N4-CH3 moiety involved in hydrophobic interactions with the side chain C of Lysβ254, Alaβ250 and Leuβ248. However, this binding pocket in tubulin is relatively large. We designed a variety of N4-alkyl substitutions to determine optimal size of the substituent at the N4-position for these hydrophobic interactions. Among the different substitutions at the N4 were n-propyl, i-propyl and cyclopropyl. These compounds inhibited the growth of human breast cancer cell line MDA-MB-435 in culture, with IC50’s 130, 410, and 300nM, respectively. The previously reported methyl substituent at the N4-position is the most potent analog against these cancer cells, with IC50 of 10.6 nM. Thus, increasing the size of the N4-alkyl substituent caused a decrease in the potency of the analogs indicating that groups larger than methyl may be progressively detrimental to potency. This could be due to conformational restriction of various rotatable bonds in the molecule, lack of appropriate hydrophobic interactions with the colchicine site, and/or due to other factors such as transport into the tumor cells. The experiments to distinguish among these possibilities are undergoing. Citation Format: Aleem Gangjee, Weiguo Xiang, Susan L. Mooberry, Ernest Hamel. Structure-activity relationship study anti-microtubule agents targeting the colchicine site on tubulin that circumvent drug resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4492. doi:10.1158/1538-7445.AM2013-4492