tbuckley/cabot-search huggingface dataset:
Selling research, and it pays.
Authors: B. Dixon
Journal: BMJ (1988)

While conceding that time has proven him wrong in doubting public acceptance of the idea of the "science shops," first sponsored by the Free University of Amsterdam to provide access to technical expertise for customers who could not afford more orthodox services, the author remains convinced that the somewhat analogous concept of "fee for service research," which offers experimental medical treatments for those who can afford to pay for them, is wrong. Such research has been justified as a private sector enterprise that provides patients who are unresponsive to standard forms of therapy with scientifically sound experimental options. However, the objections that such work might be kept secret and not contribute to medical knowledge, and that therapy would be available only to the rich, remain unanswered and pose an insurmountable obstacle to the support of this idea.
964. Combinatorial Process for Engineering Specific Meganucleases with Tailored Specificities toward a Natural Target in the XPC Gene
Authors: Christophe Perez, Sylvain Arnould, Julie Smith, Sylvestre Grizot, Agnes Gouble, Philippe Duchateau, Frederic Paques
Journal: Molecular Therapy (2006)

Xeroderma pigmentosum (XP) is a rare disease transmitted in an autosomal recessive manner Patients have an extreme sensitivity to sunlight and develop serious sunburns with onset of poikilodermia in the light-exposed skin. Skin cancers already appear in childhood, and the disease can also be associated with neurological defects. XP results from defects in the Nucleotide Excision Repair (NER) pathway, a DNA maintenance system which removes UV induced DNA damage such as cyclobutane pyrimidine dimers. XP Patients were assigned to 7 complementation groups (XP-A to XP-G), each complementation group resulting from mutations in a distinct NER gene. There is no treatment, and the majority of patients die before reaching adulthood because of metastases. However, skin engraftment can be made locally, but with the general limitations of grafts. Thus gene and cell therapy represents a huge hope for this kind of disease. Meganucleases are at the basis of a new kind of gene therapy for inherited monogenic disease, based on gene correction instead of gene complementation. These sequence-specific endonucleases can stimulate homologous gene targeting by several orders of magnitude, thereby enabling the correction of mutated genes with significant efficiency. Recently, meganucleases have been used to induce targeted recombination events in mouse hepatocytes with high efficiency, paving the way for therapeutic applications. One of the major challenges is to tailor artificial meganucleases cleaving the gene of interest, while keeping high levels of specificity. We have used a semi-rational approach to produce meganucleases targeting the XPC gene. These novel meganucleases display high levels of activity and specificity. Such results identify modularity of different functional subdomains in the I-CreI DNA-binding scaffold that can be modified without altering the overall structure, and be combined to achieve novel specificities.
SEPTIC THROMBOSIS OF THE LATERAL SINUS IN CHILDREN
Authors: D. Guthrie, D. S. Middleton
Journal: BMJ (1931)

quences.There is no need to emphasize the necessity for care in the feeding of the mother and young child.Milk and cod-liver oil help to produce well-calcified teeth.Hard food develops the jaws, and allows room for the full complement of thirty-two teeth.Apples and other fruit cleanse the teeth from acid-producing carbohydrates.Should decay occur, whether it be in deciduous or in permanent teeth, the sooner the child is brought to the dentist the better.It is far easier for the medical profession than.for the dentists to educate the public and stamp out the wicked fallacy that the first teeth do not matter much.The advent of the specialist has robbed us to some extent of the family doctor who cared for his patients from the cradle to the grave, and whose advice was as freely given to avoid disease and deformity as to effect a cure when they were present; but even now there are many opportunities in which a few timely words from the doctor could save his patients from many of the deformities of mal-occlusion, which are very real, and none the less serious because they are so common.
Upregulation of the immunoproteasome in peripheral blood mononuclear cells of patients with IgA nephropathy
Authors: Rosanna Coppo, Roberta Camilla, Alda Alfarano, Sabrina Balegno, Domenico Mancuso, Licia Peruzzi, Alessandro Amore, Antonio Dal Canton, Vincenzo Sepe, Pierangelo Tovo
Journal: Kidney International (2008)
Nutritional Deficiency of Folic Acid
Authors: J. Forshaw
Journal: BMJ (1965)

orientating teaching to their problems.A lot less of " This is a Charcot's knee, a good case for the students " and much more of " This is an overweight lady with backache, a must for the students."Consultants could then help with patients who have not responded to the practitioner's efforts and have more time for their in-patient work.-Iam, etc.,
Review: Tamoxifen, raloxifene, and tibolone prevent primary invasive breast cancer but increase risk for adverse outcomes
Authors: Joy Melnikow
Journal: Annals of Internal Medicine (2010)

ACP Journal Club16 March 2010Review: Tamoxifen, raloxifene, and tibolone prevent primary invasive breast cancer but increase risk for adverse outcomesJoy Melnikow, MD, MPHJoy Melnikow, MD, MPHUniversity of California, Davis, Sacramento, California, USA (J.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-6-201003160-02004 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationNelson HD, Fu R, Griffin JC, et al. Systematic review: comparative effectiveness of medications to reduce risk for primary breast cancer. Ann Intern Med. 2009; 151:703−15. https://pubmed.ncbi.nlm.nih.gov/19920271Clinical Impact RatingsGIM/FP/GP: References1 Melnikow J, Kuenneth C, Helms LJ, et al. Chemoprevention: drug pricing and mortality: the case of tamoxifen. Cancer. 2006;107:950-8. [PMID: 16865680] Google Scholar2 Melnikow J, Birch S, Slee C, et al. Tamoxifen for breast cancer risk reduction: impact of alternative approaches to quality-of-life adjustment on cost-effectiveness analysis. Med Care. 2008;46:946-53. [PMID: 18725849] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of California, Davis, Sacramento, California, USA (J.M.)This article was published at Annals.org on 2 March 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCombined effects of goserelin and tamoxifen on estradiol level, breast density, and endometrial thickness in premenopausal and perimenopausal women with early-stage hormone receptor-positive breast cancer: a randomised controlled clinical trial 16 March 2010Volume 152, Issue 6Page: JC3-4KeywordsBreast cancerCancer preventionCataractsChemopreventionDrugsStrokeSystematic reviewsVenous thromboembolism ePublished: 16 March 2010 Issue Published: 16 March 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A, and PECAM-1
Authors: Abigail Woodfin, Mathieu-Benoit Voisin, Beat A. Imhof, Elisabetta Dejana, Britta Engelhardt, Sussan Nourshargh
Journal: Blood (2009)
Colonic diverticular hemorrhage: the hood method for detecting responsible diverticula and endoscopic band ligation for hemostasis
Authors: Soichiro Shibata, Takashi Shigeno, Kazuya Fujimori, Keita Kanai, Kaname Yoshizawa
Journal: Endoscopy (2013)

<b>Background and study aims:</b> Although colonic diverticular hemorrhage is a common cause of lower gastrointestinal bleeding, the low rate of detection of the diverticula responsible for bleeding, together with inadequate evaluation of endoscopic hemostasis, remain unsatisfactory. <b>Patients and methods:</b> Over 3 years, we employed the hood method to diagnose diverticular hemorrhage in 53 patients and applied endoscopic band ligation (EBL) for hemostasis in 27 patients with responsible diverticula. <b>Results:</b> The hood method revealed active bleeding in 13 patients (24.5 %), nonbleeding visible vessels in 14 patients (26.4 %), and presumptive diverticular hemorrhage in 26 patients (49.1 %). The nonbleeding visible vessels were located in the diverticular dome in 13 patients and at the diverticular orifice in one patient. EBL was performed in 27 patients, and a hemostasis rate of 96.3 % was achieved. In 9 of 12 patients treated with EBL, follow-up colonoscopy revealed resolution of the responsible diverticula. <b>Conclusions:</b> The hood method improves the detection rate of diverticula responsible for bleeding by revealing potential nonbleeding visible vessels in the diverticular dome. EBL may become an effective procedure for hemostasis of colonic diverticular hemorrhage.
THE EFFECTS OF AN ACUTE REDUCTION IN BLOOD PRESSURE BY MEANS OF DIFFERENTIAL SPINAL SYMPATHETIC BLOCK ON THE CEREBRAL CIRCULATION OF HYPERTENSIVE PATIENTS 1
Authors: Seymour S. Kety, Benton D. King, Steven M. Horvath, William A. Jeffers, Joseph H. Hafkenschiel
Journal: Journal of Clinical Investigation (1950)

Recent observations by this group on the cerebral circulation in hypertension (1) have yielded normal values for cerebral blood flow and cerebral oxygen consumption but a marked increase in cerebrovascular resistance.Since the nature of this excessive vascular tone is obscure, it was felt that studies of its behavior during an acute fall in blood pressure might be of interest.Such studies, furthermore, should be pertinent to the rationale of therapy designed to lower the blood pressure in hypertension, since a fall in blood pressure must necessarily be accom- panied by a comparable embarrassment of the cere- bral circulation except insofar as the high cere- brovascular tone were capable of compensatory re- laxation.Differential spinal sympathetic block, achieved by the injection of dilute procaine solution into the lumbar subarachnoid space (2), produces a con- siderable fall in the blood pressure of many hyper- tensive patients, presumably by blocking the sym- pathetic outflow to the abdomen and lower ex- tremities without loss of skeletal muscle tone.This procedure, therefore, offers a means of study- ing the response of the cerebral circulation to a drop in blood pressure mediated by dilatation in vascular beds remote from the brain.The use of differential spinal block as a possible screening test in selecting patients for surgical sympathec- tomy provided an opportunity for undertaking these studies on the cerebral circulation.'4-N> Cl ._Cd *.A0 '4*s 0= wcE a.
Nitrous Oxide in Myocardial Infarction
Authors: John H. Eisele
Journal: JAMA (1976)

<h3>To the Editor.—</h3> The article entitled "Nitrous Oxide as an Analgesic in Acute Myocardial Infarction" (235: 924, 1976) raises some serious questions regarding the manner and safety of nitrous oxide administration in acute myocardial infarction. We have recently reported a myocardial depressant effect of nitrous oxide 40% in nine patients with documented coronary artery disease during cardiac catheterization (<i>Anesthesiology</i>44:16, 1976) compared with four patients having angina but no evidence of coronary disease by angiography. In the former group, myocardial contractility as measured by the left ventricular derivative of pressure/derivative of time (LV<sub>dpdt</sub>) at constant isometric pressure was depressed an average of 14%, left ventricular end-diastolic pressure (LVEDP) was elevated 2 mm Hg (average, 21%), while heart rate and cardiac output were not significantly changed. The four patients catheterized for angina without angiographic findings of coronary artery disease showed cardiovascular responses similar to young volunteers inhaling nitrous oxide 40%
Quality improvement report: Effect on rates of breast feeding of training for the Baby Friendly Hospital Initiative
Authors: A. Cattaneo, R. Buzzetti
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Problem:</b> Breastfeeding rates and related hospital practices need improvement in Italy and elsewhere. Training of staff is necessary, but its effectiveness needs assessment. <b>Context:</b> Eight hospitals in different regions of Italy. <b>Design:</b> Controlled, non-randomised study. Data collected in three phases. Training after the first phase in group 1 hospitals and after the second phase in group 2. <b>Strategies for change:</b> Training of trainers and subsequent training of health workers with a slightly adapted version of the 18 hour Unicef course on breastfeeding management and promotion. <b>Key measures for improvement:</b> Hospital practices, knowledge of 571 health workers, and breastfeeding rates at discharge, three, and six months in 2669 mother and baby pairs. <b>Effects of change:</b> After training hospitals improved their compliance with the "ten steps to successful breast feeding," from an average of 2.4 steps at phase one to 7.7 at phase three. Knowledge scores of health professionals increased from 0.41 to 0.72 in group 1 (training after phase one) and from 0.53 to 0.75 in group 2 (after phase two). The rate of exclusive breast feeding at discharge increased significantly after training: 41% to 77% in group 1 and 23% to 73% in group 2, as did the rates of full (exclusive plus predominant) breast feeding at three months (37% to 50% in group 1 <i>v</i> 40% to 59% in group 2) and any breast feeding at six months (43% to 62% in group 1 <i>v</i> 41% to 64% in group 2). <b>Lessons learnt:</b> Training for at least three days with a course including practical sessions and counselling skills is effective in changing hospital practices, knowledge of health workers, and breastfeeding rates.
THE CAUSATION AND TREATMENT OF RICKETS
Authors: E. Pritchard
Journal: BMJ (1919)

Tm Bo 627 opening made in the duct, and the junction reinforced by drainage wicks of gauze brought out through the abdominal incision, the whole arrangement being surrounded and isolated by omentum carefully fixed by sutures.The gauze acts as a drain for any leaking pancreatic secretion, and further sets up firm omental adhesions before its withdrawal at the end of two or three days.Neglect to isolate the drainage aperture in the way indicated may lead to serious or fatal results, for the secretion is not only in itself capable of necrosiug effects on the peri- toneum, but is in addition germ infected in many cases of pancreatitis.Drainage of the pancreas by incisions into the gland itself, while necessary in desperate cases-of acute pancreatitis, is of doubtful expediency in chlronic cases.If employed, it should be carried out only by wneans of the freest combination of large rubber tubes and ample gauze packing carefully surrounded by omentun, and, if at all possible, by the gastro-colic route, which best lends itself to such an arrangement.
Surgery for obesity in adulthood
Authors: D. R. Leff, D. Heath
Journal: BMJ (2009)

#### Summary points

The relation between morbid obesity, serious morbidity, and early mortality is well known (fig 1⇓ and table 1⇓).1 2 A recent systematic review of over 890 000 participants found that each 5 point increase in body mass index (kg/m2) over 25 was associated with a 30% increase in overall mortality.3 Conservative approaches to managing obesity (dieting, exercise, and cognitive behavioural therapy) achieve long term weight loss in only a small minority of highly motivated individuals.4 Weight loss drugs such as orlistat and sibutramine produce modest weight loss and can be prescribed only for a short time.5 Bariatric (weight loss) surgery is the only treatment that randomised controlled trials have shown to produce effective long term weight loss.6 This review provides an overview of surgical procedures for adult obesity, including results, follow-up, and complications of surgery. It focuses mainly on practice in the United Kingdom. 



Fig 1 Proportion of people with a major comorbidity, by degree of obesity. Adapted from Mokdad et al2 



View this table:

Table 1 
 Risk of developing diseases associated with obesity. Data adapted from guidance from the National Institute for Health and Clinical Excellence1



Categories of obesity are classified according to body mass index (weight(kg)/(height (m)2)) (table 2⇓). Recommendations on the management of obesity in adults are provided in guidelines published by the National Institute for Health and Clinical Excellence (NICE).1

View this table:

Table 2 
Classification of obesity based on body …
Urine Output and Fluid Therapy During Anaesthesia and Surgery
Authors: A. I. Mackenzie, J. R. Donald
Journal: BMJ (1969)

To try to determine whether fluid therapy during surgery should be on a large or a small scale 23 patients and six control subjects were studied. The control subjects were fasted and transfused with 2 litres of Ringer-lactate solution in one hour, the volume of urine output being measured at intervals for four hours. The patients were transfused similarly under varying conditions of anaesthesia and surgery. The characteristic urine output during abdominal hysterectomy followed a low, irregular pattern, and this occurred whether or not substantial amounts of fluid were transfused. In two patients anaesthesia and minimal trauma were associated with oliguria. An established diuresis was altered by anaesthesia and inhibited by surgery. These results indicate that excess Ringer-lactate solution administered during surgery may not be excreted and that overtransfusion could easily occur.
I've got a little list
Authors: J. P Koplan
Journal: BMJ (2007)

We all enjoy top 10 lists or other numerical variants, be they selections of riverside pubs, classic rock guitarists or neurosurgeons, the world's best beaches, or the Mann-Booker shortlist. Such lists allow us to focus our own views and congratulate ourselves for our good taste or astute judgment: “The list seems valid, as they chose Mark Knopfler, Jeff Beck, and Eddie Van Halen.” They also permit us to scoff at the ignorance or lack of taste of the compilers: “Where are Joe Perry, Dickie Betts, and Stephen Stills?” But I digress. 

Rarely do these lists have the explicit quantitative criteria that would satisfy a Cochrane collaborator. But the fun—and frustration—is in the subjectivity of the choices. If readers find themselves in agreement with over half the list then some modicum of satisfaction is achieved. Thus all BMJ readers will have turned, with a sense of anticipation mixed with scepticism, to the list in this supplement of the top 15 (egregious inflation of the more decimally traditional 10 or the more familiar dozen) medical milestones of the past 166 years. The list was developed by …
Ion Channels — Basic Science and Clinical Disease
Authors: Michael J. Ackerman, David E. Clapham
Journal: New England Journal of Medicine (1997)

Ion channels constitute a class of proteins that is ultimately responsible for generating and orchestrating the electrical signals passing through the thinking brain, the beating heart, and the contracting muscle. Using the methods of molecular biology and patch-clamp electrophysiology, investigators have recently cloned, expressed, and characterized the genes encoding many of these proteins. Ion-channel proteins are under intense scrutiny in an effort to determine their roles in pathophysiology and as potential targets for drugs.Defective ion-channel proteins are responsible for cystic fibrosis,1 the long-QT syndrome,2 heritable hypertension (Liddle's syndrome),3,4 familial persistent hyperinsulinemic hypoglycemia of infancy,5,6 hereditary nephrolithiasis (Dent's . . .
Tc-99m MDP Bone Imaging in Inflammatory Enthesopathy
Authors: TAMIO ABURANO, KUNIHIKO YOKOYAMA, JUNICHI TAKI, KENICHI NAKAJIMA, NORIHISA TONAMI, KINICHI HISADA
Journal: Clinical Nuclear Medicine (1990)

A case is presented in which uptake of Tc-99m MDP was noted at the sites of tendon and ligament attachments to the calcaneus in inflammatory enthesopathy. Following successful treatment with corticosteroids, the uptake was markedly decreased in accordance with subsidence of clinical manifestations and normalization of laboratory data. Radionuclide bone imaging may be useful in evaluating the response to treatment with corticosteroids as well as revealing the active disease sites in inflammatory enthesopathy.
Impact of treatment‐related liver toxicity on the outcome of HCV‐positive non‐Hodgkin's lymphomas
Authors: Luca Arcaini, Michele Merli, Francesco Passamonti, Raffaele Bruno, Ercole Brusamolino, Paolo Sacchi, Sara Rattotti, Ester Orlandi, Elisa Rumi, Virginia Ferretti, Silvia Rizzi, Erika Meli, Cristiana Pascutto, Marco Paulli, Mario Lazzarino
Journal: American Journal of Hematology (2009)

Abstract We studied 160 Hepatitis C virus (HCV)‐positive patients with NHL (59 indolent NHL, 101 aggressive). Median age was 67 years. HCV‐RNA was present in 146. HBsAg was positive in seven patients. At diagnosis, ALT value was above UNL in 67 patients. One hundred and twenty patients received an anthracycline‐based therapy, alkylators, 28 received chemotherapy plus rituximab. Cytotoxic drugs dose was reduced in 63 patients. Among 93 patients with normal ALT at presentation, 16 patients developed WHO grade II–III liver toxicity. Among 67 patients with abnormal ALT, eight patients had a 3.5 times elevation during treatment. Among 28 patients treated with rituximab and chemotherapy, five patients (18%) developed liver toxicity. Thirty four patients (21%) did not complete treatment (eight for liver toxicity). Median progression‐free survival (PFS) for patients who experienced liver toxicity is significantly shorter than median PFS of patients without toxicity (respectively, 2 years and 3.7 years, P = 0.03). After a median F‐UP of 2 years, 32 patients died (three for hepatic failure). A significant proportion of patients with HCV+ NHL develop liver toxicity often leading to interruption of treatment. This could be a limit to the application of immunochemotherapy programs. HCV+ lymphomas represent a distinct clinical subset of NHL that deserves specific clinical approach to limit liver toxicity and ameliorate survival. Am. J. Hematol., 2010. © 2009 Wiley‐Liss, Inc.
Factor-VIII-related antigen: measurement by enzyme immunoassay.
Authors: A Bartlett, K M Dormandy, C M Hawkey, P Stableforth, A Voller
Journal: BMJ (1976)

Factor-VIII-related antigen was measured, both by an enzyme immunoassay using a microplate method and by the Laurell technique, in normal people, patients with von Willebrand's disease, haemophiliacs, and obligatory haemophilia carriers. The enzyme immunoassay was simpler to perform and gave equally reliable and reproducible results. Many more assays could be carried out at any one time.