tbuckley/cabot-search huggingface dataset:
Thiotepa in Treatment of Advanced Breast Cancer
Authors: A. Lyons, G. Edelstyn
Journal: BMJ (1962)

VIRUS DISEASES MICL JOUAt a meeting recently a friend of mine produced the following quotation from J. J. Rousseau." Si quelquefois les savants ont moins de prejuges que les autres hommes, ils tiennent en revanche, encore plus fortement i ceux qu'ils ont."This is applicable to our vaccination policies.If I may translate "savants" as " doctors and scientists" the quotation could read: " If doctors and scientists have fewer prejudices than other men, they hold all the more strongly to the few they have.
Age related differences in the response to acidosis, hypoxia, and hyperkalaemia in canine cardiac Purkinje fibres
Authors: J C. Geller, M. R Rosen
Journal: Cardiovascular Research (1994)

Objective: In the clinical setting, the response of adult and neonatal cardiac rhythms to hypoxia and to acidosis differs, the former leading to tachyarrhythmias and the latter to bradyarrhythmias. In this study, the aim was to determine whether a cellular electrophysiological substrate could be identified to explain the clinical observation. Methods: Conventional microelectrode techniques were used to study the electrophysiological responses of automatic Purkinje fibres to acidosis, hypoxia, and hyperkalaemia individually. Results: Adult Purkinje fibres showed decreases in maximum diastolic potential, activation voltage, and automaticity as pH was decreased from 7.3 to 6.1. Triggered activity due to early afterdepolarisations developed in 70% of adult Purkinje fibres at pH 6.1. Neonatal Purkinje fibres showed decreased automaticity as pH decreased and, in contrast to adults, quiescence occurred at pH 6.1 At Po2 <2.9 kPa automaticity decreased significantly in adult Purkinje fibres, whereas neonatal fibres were unaffected. The effect of raising [K+]o was comparable at both ages. Conclusions: The response to acidosis and to hypoxia differs significantly between neonatal and adult Purkinje fibres and may explain some developmental differences in the expression of cardiac arrhythmias. Cardiovascular Research 1994;28:125-128
Hepatitis C virus (HCV) protein expression enhances hepatic fibrosis in HCV transgenic mice exposed to a fibrogenic agent
Authors: Philippe Chouteau, Nicole Defer, Alexandre Florimond, Julien Caldéraro, Martin Higgs, Aurore Gaudin, Emilie Mérour, Daniel Dhumeaux, Hervé Lerat, Jean-Michel Pawlotsky
Journal: Journal of Hepatology (2012)
INFO GRAPHIC TEST 2014
Authors: A. Rimmer
Journal: BMJ (2014)

Projects to improve survival after cardiac arrests that occur outside hospitals, to spot chronic lung disease, and to reduce pressure on hospital emergency services scooped the top prizes at The BMJ Awards 2014 last night.

The awards, sponsored by the Medical and Dental Defence Union of Scotland (MDDUS), took place at the Westminster Park Plaza Hotel, London, and was hosted by the broadcaster Gyles Brandreth. Other winners included a team providing training in keyhole surgery in Tanzania and a trial of treatment for HIV positive babies and children in developing countries.

The Lifetime Achievement Award went to Iain Chalmers, co-founder of the Cochrane Collaboration and coordinator of the James Lind Initiative, for his contribution to improving health across the world.

Fiona Godlee, The BMJ ’s editor in chief, said of Chalmers: “He brings to everything he does a …
The Epidemiology of Microscopic Colitis in Olmsted County From 2002 to 2010: A Population-Based Study
Authors: Nicole M. Gentile, Sahil Khanna, Edward V. Loftus, Thomas C. Smyrk, William J. Tremaine, W. Scott Harmsen, Alan R. Zinsmeister, Patricia P. Kammer, Darrell S. Pardi
Journal: Clinical Gastroenterology and Hepatology (2013)
Fetal Growth and Prenatal Exposure to Bisphenol A: The Generation R Study
Authors: Claudia A. Snijder, Dick Heederik, Frank H. Pierik, Albert Hofman, Vincent W. Jaddoe, Holger M. Koch, Matthew P. Longnecker, Alex Burdorf
Journal: Environmental Health Perspectives (2013)

Prenatal exposure to bisphenol A (BPA) has been associated with adverse birth outcomes, but findings of previous studies have been inconsistent.We investigated the relation of prenatal BPA exposure with intrauterine growth and evaluated the effect of the number of measurements per subject on observed associations.This study was embedded in a Dutch population-based prospective cohort study, with urine samples collected during early, mid-, and late pregnancy. The study comprised 219 women, of whom 99 had one measurement, 40 had two measurements, and 80 had three measurements of urinary BPA. Fetal growth characteristics were repeatedly measured by ultrasound during pregnancy and combined with measurements at birth. Linear regression models for repeated measurements of both BPA and fetal growth were used to estimate associations between urinary concentrations of creatinine-based BPA (BPACB) and intrauterine growth.The relationship between BPACB and fetal growth was sensitive to the number of BPA measurements per woman. Among 80 women with three BPA measurements, women with BPACB > 4.22 μg/g crea (creatinine) had lower growth rates for fetal weight and head circumference than did women with BPACB < 1.54 μg/g crea, with estimated differences in mean values at birth of -683 g (20.3% of mean) and -3.9 cm (11.5% of mean), respectively. When fewer measurements were available per woman, the exposure-response relationship became progressively attenuated and statistically nonsignificant.Our findings suggest that maternal urinary BPA may impair fetal growth. Because previous studies have shown contradictory findings, further evidence is needed to corroborate these findings in the general population.
Dietary Calcium and Blood Pressure
Authors: Heiner C. Bucher
Journal: Annals of Internal Medicine (1997)

Letters15 March 1997Dietary Calcium and Blood PressureHeiner C. Bucher, MD, Gordon H. Guyatt, MD, and Richard J. Cook, MDHeiner C. Bucher, MDMedizinische Universitats-Poliklinik, Kantonsspital, Basel, SwitzerlandMcMaster University, Hamilton, Ontario, CanadaUniversity of Waterloo, Kitchener, Ontario, CanadaSearch for more papers by this author, Gordon H. Guyatt, MDMedizinische Universitats-Poliklinik, Kantonsspital, Basel, SwitzerlandMcMaster University, Hamilton, Ontario, CanadaUniversity of Waterloo, Kitchener, Ontario, CanadaSearch for more papers by this author, and Richard J. Cook, MDMedizinische Universitats-Poliklinik, Kantonsspital, Basel, SwitzerlandMcMaster University, Hamilton, Ontario, CanadaUniversity of Waterloo, Kitchener, Ontario, CanadaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-6-199703150-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Allender and colleagues [1] investigated the relation of dietary calcium intake and blood pressure in a meta-analysis of randomized, controlled trials. They found that calcium supplementation decreased blood pressure by a greater amount in trials in which the mean blood pressure was greater than 130 mm Hg than in trials in which it was less than 130 mm Hg (change of −1.68 mm Hg [95% CI, −3.18 to −0.18 mm Hg] compared with change of −0.53 mm Hg [CI, −1.56 to 0.49 mm Hg]). We believe the inference that the hypotensive effect of calcium is greater in ...References1. Allender PS, Cutler JA, Follmann D, Cappuccio FP, Pryer J, Elliot P. Dietary calcium and blood pressure: a meta-analysis of randomized clinical trials. Ann Intern Med. 1996; 124:825-31. Google Scholar2. Bucher HC, Cook RJ, Guyatt GH, Lang JD, Cook DJ, Hatala R, et al. Effects of dietary calcium supplementation on blood pressure. JAMA. 1996; 275:1016-22. Google Scholar3. Oxman AD, Guyatt GH. A consumer's guide to subgroup analysis. Ann Intern Med. 1992; 116:78-84. Google Scholar Author, Article, and Disclosure InformationAffiliations: Medizinische Universitats-Poliklinik, Kantonsspital, Basel, SwitzerlandMcMaster University, Hamilton, Ontario, CanadaUniversity of Waterloo, Kitchener, Ontario, Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDairy Foods and HypertensionDairy Foods and Hypertension 15 March 1997Volume 126, Issue 6Page: 492KeywordsBlood pressureCalciumRandomized trialsRegression analysisSystematic reviewsSystolic pressure Issue Published: 15 March 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Control of paraquat.
Authors: A J Cole, J B Hawkins, P P Mayer
Journal: BMJ (1971)

sive sweat causes incomplete recording of the finger impression.Further, "white lines" are common in normal people, particularly in those following certain occupations-for example, bricklayers, cement workers and housewives.These lines quickly disappear during periods of interruption of the relevant employment.Improvements observed during periods of treatment probably relate to con- comitant change in occupation rather than to the dietary management.-Weare, etc.,
555. Large-Scale, Flow-Based Electroporation To Deliver Engineered Zinc Finger Protein Nucleases That Mediate High-Efficiency Disruption of the Human CCR5 Gene
Authors: Michae lC. Holmes, Linda Liu, Elena Perez, Linhong Li, Rama Shivakumar, Cornell Allen, Olga Liu, Jeffrey C. Miller, Fyodor D. Urnov, Kenneth Kim, Edward J. Rebar, Dale Ando, Philip D. Gregory, James Riley, Madhusudan Peshwa, Carl June
Journal: Molecular Therapy (2006)

The identification of the chemokine receptor CCR5 as the major co-receptor required for HIV entry into CD4 T-cells has made the targeted disruption of CCR5 an attractive potential therapeutic approach for treating HIV-infected patients. Yet, no current method permits the efficient therapeutic disruption of a chosen gene in the human genome. We have developed designed zinc-finger protein nucleases (ZFNs) that specifically target the coding sequence of the CCR5 gene. Using standard delivery methods, we have shown these ZFNs can efficiently stimulate the formation of a double strand break (DSB) in the CCR5 locus to allow the natural DNA repair pathways, including Non-Homologous End Joining (NHEJ), to subsequently repair the DSB. Importantly, however, NHEJ is error prone and thus can result in frameshift mutations, leading to permanent disruption in >10% of K562 cells. To take this technology toward clinical application we sought a delivery mode that could transiently deliver the ZFNs to large numbers of primary human T-cells without disrupting their normal cellular functions. In this regard we tested the ability of a scalable, flow-based electroporation device to deliver the CCR5-ZFNs at high efficiency to K562 cells and primary human T-cells. This closed, sterile system allows for consistent delivery of the CCR5- ZFN expression plasmid to >1×10e9 cells. Initial experiments showed this approach could disrupt >20% of the CCR5 alleles in K562 cells and >5% in primary human T-cells. The frequency of gene disruption observed supports the examination of this approach as a possible method for the therapeutic modification of isolated patient cells to generate HIV-resistant T-cells. We will present data on the development of this approach in model systems and in primary human T-cells. I am a full-time employee of Sangamo BioSciences.
The FDA and Drug Marketing Expenditures-Reply
Authors: David A. Kessler
Journal: JAMA (1991)

<h3>In Reply. —</h3> There is no question that the pharmaceutical industry spends large amounts of money promoting prescription medication. Some estimate about $5 billion is expended each year on pharmaceutical marketing and advertising. Dr Joseph suggests that this expenditure adds to the cost of pharmaceuticals. Indeed, it must. However, it would be incorrect to assume that there are altogether no societal benefits to this expenditure. The rapid adoption of new therapies often is directly attributable to promotional activities of the industry, and some experts contend that advertising is a cost-effective mechanism for communicating important product information. Although some countries limit the amount of money a drug company can spend on advertising, in a free market each company sets its own promotional budget. The FDA's legal mandate is to ensure that the information contained in pharmaceutical promotions is not false or misleading. The agency has no legal authority to limit drug
Doxorubicin-induced alterations of the gene expression profiles of leukemia cells in culture using cDNA microarrays
Authors: Antoine Vekris, François Godard, Marie-Christine Haaz, Jacques Robert, Jacques Bonnet
Journal: Nature Genetics (2001)

A subset of breast cancer patients (14% of our data set) neoadjuvantly treated with epirubicin-based chemotherapy experience complete remission associated with prolonged survival.Based on massively parallel transcriptome analysis, we describe for the first time early in situ effects of epirubicin-based chemotherapy in a neoadjuvant setting.We took jet-needle biopsies from 22 individual tumors immediately before and 24 h after the first cycle of chemotherapy.Clontech's 1.2 human cancer complementary DNA arrays were used.Jet-needle biopsies (30 mm 3 ) yielded sufficient material (20-60 µg total RNA) for gene expression profiling.Of 1,185 genes selected for the array 30-50% were expressed.The most prominent early effect of chemotherapy was an upregulation of the cyclin kinase inhibitor WAF1, an important regulator of the G1-S transition in 82% of the tumors (average induction 2.8-fold; range 1.5-to 7-fold).Of the other cyclin kinase inhibitors, only p16-INK4A and p57-KIP2 were upregulated in a small subset of tumors.We observed a moderate chemotherapy-induced upregulation of various DNA repair enzymes.This group included XPC, an initiator of global genome nucleotide excision repair; endonuclease III homologue 1 (HNTH1) and DNA-damage-inducible transcript 3 (DDIT3, GADD153).Preliminary supervised cluster analysis seems to be encouraging for response prediction.Jetneedle technology is appropriate for in situ response monitoring in neoadjuvantly treated breast cancer patients.Chemotherapy-induced effects on cellcycle control and DNA repair could be demonstrated as early as 24 hrs after the onset of therapy.
Subcutaneous calcium heparin versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs:: Authors' reply
Authors: M G Walker, J W Shaw, G J L Thomson, J G R Cumming, M L. Thomas
Journal: BMJ (1987)

findings from the Office of Population Censuses and Surveys' longitudinal study that unemployment in the early 1980s is associated with increased mortality.
323 Nutrition is more important than TH1-dominated condition for better response in interferon alpha-2B/ribavirin therapy
Authors: A OKUMURA, T ISHIKAWA, M AYADA, K SATO, T MAENO, N HOTTA, T TAGAYA, Y FUKUZAWA, K SHINICHI
Journal: Hepatology (2003)

The ability to obtain primary long-term cultures of human foetal hepatocytes maintaining liver differentiation characteristics in serum-free medium prompted us to test their susceptibility to hepatitis C virus infection. Using PCR, we detected the presence of the HCV RNA-positive strand in the supernatants and in the cells of the virus-infected hepatocyte cultures, at various times post-infection. Evidence of effective virus genome replication and multiplication was also based on the time-dependent appearance of the putative HCV RNA-negative strand, the detection of virus replicative intermediates and an increase in HCV genomic templates in the HCV-infected cells.
ABC of intensive care: Other supportive care
Authors: S. Adam, S. Forrest
Journal: BMJ (1999)

As well as specific organ support techniques such as mechanical ventilation and renal replacement therapy, patients in intensive care require other interventions to maintain organ function and prevent further damage. These include nutritional support, preserving skin integrity, psychological support, and mobilisation. These interventions enable patients to recover their previous level of health, prevent intercurrent problems such as nosocomial infection and lung atelectasis, and support psychological and physical wellbeing.



Intensive care is not just about organ support



Patients who are intubated or mechanically ventilated require chest physiotherapy to remove excess bronchial secretions, re-expand atelectatic areas, improve ventilation, decrease ventilation-perfusion mismatch, and mobilise the thoracic cage.

#### Respiratory complications associated with tracheal intubation and mechanical ventilation

Bronchial secretions increase in intubated patients as the tracheal mucous membrane is irritated. These secretions may become tenacious as the patients' natural humidification has been bypassed. Expectoration may also be reduced by an ineffective cough, decreased ciliary action, and loss of sigh breaths.

Secretion tenacity can be reduced by adequate humidification and systemic hydration. Clearance of secretions is achieved by chest physiotherapy, suctioning, and occasionally bronchial lavage.



Manual hyperinflation improves lung compliance and arterial oxygenation



#### Disadvantages of immobility

##### Cardiovascular

##### Respiratory

##### Metabolic

##### Musculoskeletal

The primary aims of chest physiotherapy are to improve gas exchange and prevent atelectasis and consolidation, which occur as a result of mucus plugging or infection. Patients are assessed daily and will receive the following treatments as appropriate.

Positioning —For postural drainage or to improve ventilation-perfusion matching.

Manual …
Insulin Sensitivity, Glucose Effectiveness, and Body Fat Distribution Pattern in Nondiabetic Offspring of Patients With NIDDM
Authors: Kwame Osei, Daryl A Cottrell, Martha M Orabella
Journal: Diabetes Care (1991)

Objective To determine the relationship of insulin sensitivity (SI), glucose effectiveness (glucose-dependent glucose transport [SG]), and body fat distribution patterns in glucose-tolerant offspring of patients with non-insulin-dependent diabetes mellitus (NIDDM). Research Design and Methods Ten glucose-tolerant offspring of patients with NIDDM and 10 age-, sex-, and weight-matched healthy control subjects without family history of diabetes were studied with the minimal model method of Bergman et al. Body fat composition and distribution pattern were assessed by the bioelectrical impedance analyzer and waist-hip circumference ratios (WHR), respectively, in each subject. Results Mean fasting serum glucose (4.39 ± 0.17 vs. 3.94 ± 0.17 mM) and postglucose peak (18.50 ± 1.50 vs. 13.20 ± 1.06 mM) levels were significantly greater (P &amp;lt; 0.05) in the offspring than in the control subjects. Mean fasting serum insulin levels were slightly greater but not significantly different in the offspring versus control subjects (64 ± 14 vs. 29 ± 7 pM). After intravenous stimulation with glucose and tolbutamide, the mean serum insulin rose to significantly greater (P &amp;lt; 0.05) levels at t = 5 and 25 min in the offspring compared with the control subjects. Mean SI was significantly reduced by 45% in the offspring compared with the control subjects (4.77 ± 0.67 vs. 8.37 ± 1.24 × 10-4 min−1 · mU-1 · L-1;). However, SG was not different in the offspring versus control subjects (1.92 ± 0.12 vs. 2.10 ± 0.17 × 10-2 min−1). SI correlated significantly and inversely with the percentage of body fat mass (r = −0.580, P &amp;lt; 0.05) but not with the WHR (r = −0.019) in the offspring. We found a negative association between SI and basal serum insulin (r = −0.798, P &amp;lt; 0.01) but not with the poststimulation incremental insulin responses in the offspring. Family history of diabetes independently accounted for at least 27% of variance in the SI in our subjects. Conclusions Our study confirmed that insulin insensitivity but not a reduced glucose effectiveness exists in young glucose-tolerant offspring of patients with NIDDM. The reduced SI appears to be causally related to the total body fat content and may be a familial and/or genetic trait in the offspring.
Association Between Major Depressive Episodes in Patients With Chronic Kidney Disease and Initiation of Dialysis, Hospitalization, or Death
Authors: S. Susan Hedayati, Abu T. Minhajuddin, Masoud Afshar, Robert D. Toto, Madhukar H. Trivedi, A. John Rush
Journal: JAMA (2010)

Patients with chronic kidney disease (CKD) experience increased rates of hospitalization and death. Depressive disorders are associated with morbidity and mortality. Whether depression contributes to poor outcomes in patients with CKD not receiving dialysis is unknown.To determine whether the presence of a current major depressive episode (MDE) is associated with poorer outcomes in patients with CKD.Prospective cohort study of 267 consecutively recruited outpatients with CKD (stages 2-5 and who were not receiving dialysis) at a VA medical center between May 2005 and November 2006 and followed up for 1 year. An MDE was diagnosed by blinded personnel using the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.The primary outcome was event-free survival defined as the composite of death, dialysis initiation, or hospitalization. Secondary outcomes included each of these events assessed separately.Among 267 patients, 56 had a current MDE (21%) and 211 did not (79%). There were 127 composite events, 116 hospitalizations, 38 dialysis initiations, and 18 deaths. Events occurred more often in patients with an MDE compared with those without an MDE (61% vs 44%, respectively, P = .03). Four patients with missing dates of hospitalization were excluded from survival analyses. The mean (SD) time to the composite event was 206.5 (19.8) days (95% CI, 167.7-245.3 days) for those with an MDE compared with 273.3 (8.5) days (95% CI, 256.6-290.0 days) for those without an MDE (P = .003). The adjusted hazard ratio (HR) for the composite event for patients with an MDE was 1.86 (95% CI, 1.23-2.84). An MDE at baseline independently predicted progression to dialysis (HR, 3.51; 95% CI, 1.77-6.97) and hospitalization (HR, 1.90; 95% CI, 1.23-2.95).The presence of an MDE was associated with an increased risk of poor outcomes in CKD patients who were not receiving dialysis, independent of comorbidities and kidney disease severity.
More than 200 000 people ask Novartis to drop its challenge on drug patent
Authors: Sally Hargreaves
Journal: BMJ (2007)

As the Indian High Court this week postponed the hearing of the legal challenge by the Swiss drug company Novartis against the Indian government over its refusal to grant the company a patent on imatinib (Glivec), nearly a quarter of a million people from more than 150 countries signed an international petition calling for Novartis to back down. 

Unni Karunakara, from the charity Medecins Sans Frontieres, said at a press briefing this week in New Delhi: “Over 80% of the medicines we use to treat AIDS patients come from India, and access to affordable and new drugs for HIV is now becoming imperative as drug resistance grows . . . Sixty seven per cent of India's generic drug exports go …