tbuckley/cabot-search huggingface dataset:
Comment on: Chakkera et al. Can New-Onset Diabetes After Kidney Transplant Be Prevented? Diabetes Care 2013;36:1406–1412
Authors: Manfred Hecking, Adnan Sharif, Friedrich K. Port, Marcus D. Säemann
Journal: Diabetes Care (2013)

“To a man with a hammer, everything looks like a nail” is a popular metaphor attributed to Mark Twain, also known as the “law of the instrument” and presented in Maslow’s The Psychology of Science : A Reconnaissance (1). Being ourselves guilty or not of “using only one hammer, and seeing nothing but nails,” we would like to comment on the recent review of Chakkera et al. on new-onset diabetes after transplantation (NODAT) (2).

The authors have described our prior proof-of-concept study on early posttransplant insulin administration (3), which has become the basis for currently ongoing NODAT prevention trials exploring strategies of insulin administration (clinical trial reg. nos. NCT01683331 and NCT01680185). Contrasting …
Incidence of Presentation of Common Functional Gastrointestinal Disorders in Children From Birth to 5 Years: A Cohort Study
Authors: Denesh K. Chitkara, Nicholas J. Talley, Amy L. Weaver, Slavica K. Katusic, Heiko De Schepper, Mary Jo Rucker, G. Richard Locke
Journal: Clinical Gastroenterology and Hepatology (2006)
Targeted disruption of the murine cholecystokinin-1 receptor promotes intestinal cholesterol absorption and susceptibility to cholesterol cholelithiasis
Authors: David Q.-H. Wang, Frank Schmitz, Alan S. Kopin, Martin C. Carey
Journal: Journal of Clinical Investigation (2004)

Cholecystokinin (CCK) modulates contractility of the gallbladder, the sphincter of Oddi, and the stomach. These effects are mediated through activation of gastrointestinal smooth muscle as well as enteric neuron CCK-1 receptors (CCK-1Rs). To investigate the potential physiological and pathophysiological functions linked to CCK-1R–mediated signaling, we compared male WT and CCK-1R–deficient mice (129/SvEv). After 12 weeks on either a standard mouse chow or a lithogenic diet (containing 1% cholesterol, 0.5% cholic acid, and 15% dairy fat), small-intestinal transit time, intestinal cholesterol absorption, biliary cholesterol secretion, and cholesterol gallstone prevalence were compared in knockout versus WT animals. Analysis of mice on either the chow or the lithogenic diet revealed that CCK-1R–/– animals had larger gallbladder volumes (predisposing to bile stasis), significant retardation of small-intestinal transit times (resulting in increased cholesterol absorption), and increased biliary cholesterol secretion rates. The elevation in bile cholesterol, coupled with a tendency toward gallbladder stasis (due to the absence of CCK-induced contraction), facilitates nucleation, growth, and agglomeration of cholesterol monohydrate crystals; this sequence of events in turn results in a significantly higher prevalence of cholesterol gallstones in the CCK-1R–null mice.
Skin barrier function in healthy volunteers as assessed by transepidermal water loss and vascular response to hexyl nicotinate: intra- and inter-individual variability
Authors: E. OESTMANN, A.P.M. LAVRIJSEN, J. HERMANS, M. PONEC
Journal: British Journal of Dermatology (1993)

This study assesses the variability of two non-invasive methods of measuring stratum corneum barrier function in vivo. Transepidermal water loss (TEWL), and the vascular response to hexyl nicotinate (HN) penetration as determined by laser-Doppler flowmetry, were measured in a group of 21 healthy volunteers. Each time profile of the vascular response to HN penetration was analysed using the following parameters: the baseline cutaneous blood flow, the lag-time between application and initial response (to), the time between application and maximum response (tmax.), the maximum response, and the slope of the curve. TEWL measured on the left volar forearm showed a normal range of 3.9–7.6 g/m2h and a small inter-individual variability [coefficient of variation (CV) 19–4%]. TEWL values at three other forearm sites did not show differences of clinical importance compared with the left volar forearm. The parameters of the vascular response to HN penetration spanned a wider normal range than the TEWL values (CV between 33 and 52%). Repeat measurements after a 1–2 month interval showed highly reproducible individual TEWL values. The mean difference between first and second measurements was only 0.03 g/m2h: the relative difference 0.6%. The intra-individual reproducibility of to and tmax for HN penetration was also high (relative differences of 2.8 and 3.1%, respectively). The other vascular response parameters were less reproducible (relative differences of 6.9–18.6%). We conclude that TEWL and selected parameters of HN penetration, as non-invasive tests of the stratum corneum barrier function, yield reproducible results and are hence useful for investigations assessing the skin barrier function in various disorders.
Abstract P5-08-05: The influence of doxorubicin on PTEN and PI3K-Akt-mTOR signaling in human breast cancer
Authors: E Austreid, S Knappskog, PE Lønning, HP Eikesdal
Journal: Cancer Research (2013)

Abstract Background: De novo as well as acquired resistance are common features of anthracycline therapy in breast cancer. The PTEN tumor suppressor gene is frequently inactivated in human breast cancer, leading to induction of PI3K-Akt-mTOR signaling, which facilitates cell growth, survival, invasion and ultimately tumor progression. Upregulation of the PI3K-Akt-mTOR pathway has been suggested as a possible mechanism of anthracycline resistance, but there is limited data in the clinical setting, including its influence on PTEN expression. Methods: The early PTEN response to doxorubicin was assessed in vitro in MCF7 (estrogen receptor positive) and MDA-MB231 (triple negative) human breast cancer cell lines 24 hours after the initiation of chemotherapy. Tumor samples from thirty patients with locally advanced breast cancer were analyzed for PTEN expression levels and PI3K-Akt-mTOR signaling before and after neoadjuvant anthracycline therapy. The early effect of anthracyclines on PTEN expression is currently being evaluated in human breast cancer samples 24 hours after the initiation of chemotherapy. Mice bearing MCF7 and MDA-MB231 xenografts will be used to assess the potential of PI3K-Akt-mTOR signal transduction inhibitors in preventing anthracycline resistance. Results: PTEN expression was found to be profoundly downregulated in both MCF7 and MDA-MB231 cell lines, 24 hours after exposure to doxorubicin at their respective IC50. An increase in Akt1 protein levels in both cell lines was observed in the same setting. In 19 out of 30 human breast cancers PTEN levels increased after a median of 16 weeks neoadjuvant doxorubicin treatment. No difference between estrogen receptor positive and negative breast cancers was observed. The increase in PTEN was accompanied by an increase in fibrotic tissue in the tumor interior. There was no correlation between PTEN level or treatment-induced alterations in PTEN expression and response rates or recurrence-free survival (RFS). The results from our currently ongoing experiments will be presented. Conclusion: PTEN expression increases in the majority of human breast cancers during long-term exposure to doxorubicin. However, PTEN is greatly downregulated, with corresponding Akt1 increase, 24 hours after exposure to high doses of doxorubicin in vitro. These results indicate different effects of short- and long-term exposure to doxorubicin, which may be of importance to the development of anthracycline resistance, and to understand at what time a combinational approach with inhibitors of the PI3K-Akt-mTOR pathway will be beneficial. Current efforts are aimed at evaluating the potential of such inhibitors to counteract doxorubicin resistance in this setting. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-08-05.
What should clinicians do when faced with conflicting recommendations?
Authors: A. D Oxman, P. Glasziou, J. W Williams
Journal: BMJ (2008)

Find guidelines that are systematic and transparent, and make informed judgments

Clinical practice guidelines sometimes make conflicting recommendations.1 2 3 4 5 6 7 8 For example, a sore throat may be managed differently in North America, France, and Finland—where guidelines recommend that a diagnostic test should be performed and that treatment should be conditional on its result—than it would be in England, Scotland, the Netherlands, and Belgium—where guidelines recommend that the decision to prescribe penicillin should depend mainly on the severity of symptoms, with no testing.1

Such disagreements occur for both valid and non-valid reasons. Valid reasons include honest differences in the many judgments that go into a recommendation—judgments about which research is relevant; the risk of bias in that research; the applicability of the research findings to the question at hand; and the relative importance of the anticipated benefits, adverse effects, and costs. Non-valid reasons include conflicts of interest, lack of awareness of relevant evidence or ignoring such evidence, failure to appraise the relevant research critically, failure to consider outcomes that are important …
Fracture of First Rib
Authors: F. I. Powell
Journal: BMJ (1950)

ENDOTHELIOMA OF THE PLEURA in size from a pinhead to 3 in.(7.6 cm.) in diameter were found.They were attached to the parietal and visceral pleurae, those on the visceral pleura extending into but not invading the lung.The four largest tumours were removed by diathermy and on section were seen to be very vascular and well encapsulated.Histologically the tumours were composed of spindle-shaped cells, in places showing a whorled arrangement and in other areas apparently lining clefts (Fig. 2).At Professor Scarff's suggestion the sections were examined by a consultant panel of pathologists, whose opinion favoured the diagnosis of endothelioma.Convalescence was uncomplicated except for the develop- ment of a complete palsy of the left vocal cord.The fever disappeared and only a small pleural effusion formed; this was soon absorbed.The patient left hospital on January 16.On May 6 she felt well, but complained of a dry cough, slight dyspnoea, and aching pain over the left lower chest.There was some note impairment over the left base, with weak breath sounds, and radiography revealed a number of rounded shadows on the left side, particularly at the left base.On July 17 she was readmitted.She was now very ill with fever, dry cough, and severe dyspnoea.The signs were little changed, and a radiograph showed a further increase in the size of the tumours and possibly some fluid in the left pleura, but no fluid was found on paracentesis.She was seen by Professor Windeyer, who agreed to give deep x-ray therapy, although it was realized that the growth was likely to be radio-insensitive.Owing to deterioration of her general condition this treatment was stopped after two applications.A fortnight before her death on August 15 she developed albuminuria and gross oedema of the trunk and legs.Necropsy.(Extract from Bland-Sutton Institute Post-mortemReport.)-The left pleura was studded with multiple nodular growths up to 2+ in.(6.35 cm.) in diameter, arising from both visceral and parietal layers, the larger ones showing central softening.The tumours had a firm grey surface on section.Those arising from the parietal pleura were polypoid and those from the visceral surface indented the lung without actual invasion.The tumours were most numerous at the base anteriorly.There was no evidence of growth in any of the bronchi or general thickening of the pleura.One gland at the bifurcation of the trachea was involved by growth.The right pleural sac contained 30 oz. (852 ml.) of clear fluid and the right lung was oedematous, but there was no growth in pleura or lung.The liver and kidneys showed amyloid change.No primary growth was found in any other organ and, apart from the one lymph node, there were no metastases.Histology.-Sections of the growth showed spheroidal eosinophil epithelioid cells with vesicular nuclei.In places there were attempts at tubule formation; elsewhere the cells were arranged in whorls.The lymph node was invaded by the growth.Our thanks are due to Dr. H. K.
The unknown risks of youth rugby
Authors: M. Carter
Journal: BMJ (2015)

And the urgent need to quantify them 

Anyone who has spent an hour picking skull fragments out of the contused frontal lobes of a teenage rugby player is entitled to an opinion on the safety of youth rugby. As a paediatric neurosurgeon, I’ve done this on several occasions. As a “rugby parent,” I’ve observed the school and club game at close quarters, from both sides of the touchline. What I’ve seen and heard suggests that our thinking on the subject may not be altogether rational.

Rugby union is a full contact collision sport in which extreme force may legitimately be exerted to acquire and maintain possession of the ball. Play exposes participants to the risk of severe physical injury. Five minutes on YouTube will show how true this is for the professional game. But rugby is also played by children, who share many of the same risks as adult players but are arguably more vulnerable physically.

In UK schools where rugby is played, it mostly begins as a near compulsory activity from the age of 8 years. By 10 years, most players engage in some form of contact competition, increasing the potential for injury. Many players are …
Targeted Chromosomal Gene Modification in Human Cells by Single-Stranded Oligodeoxynucleotides in the Presence of a DNA Double-Strand Break
Authors: Frank Radecke, Ingrid Peter, Sarah Radecke, Katharina Gellhaus, Klaus Schwarz, Toni Cathomen
Journal: Molecular Therapy (2006)

A DNA double-strand break (DSB) cannot be tolerated by a cell and is dealt with by several pathways. Here, it was hypothesized that DSB induction close to a targeted mutation in the genome of a mammalian cell might attract oligodeoxynucleotide (ODN)-directed gene repair. A HEK-293-derived cell line had been engineered harboring a single target locus with open reading frames encoding the living-cell reporter proteins LacZ and EGFP, the latter translationally decoupled by a DNA spacer with a unique I-SceI recognition site for defined DSB induction. To enable expression of a fluorescent LacZ–EGFP fusion protein, single-stranded (ss) ODNs (80 or 96 nucleotides long) spanning the DSB were designed to fuse both reading frames by altering a few base-pair positions, deleting 59 bp or introducing a 10-bp fragment. The ssODNs alone generated few EGFP-positive cells. With I-SceI transiently expressed, more than 0.3% of cells revealed EGFP expression 7 days after transfection, with up to 96% of the loci faithfully corrected, depending on the ssODN used. During these correction events, the ssODN did not become physically incorporated into the chromosome, but served only as information template. Unwanted insertional mutagenesis also occurred. Both observations have important implications for gene therapy.
Multicenter Clinical Trials of AIDS Vaccines Scheduled to Get Under Way in Coming Months
Authors: Charles Marwick
Journal: JAMA (1993)

SOME 320 volunteers, men and women from 18 to 60 years of age who are human immunodeficiency virus (HIV) antibody-negative but may belong to groups at high risk for this infection, are being recruited for clinical trials of two vaccines against the acquired immunodeficiency syndrome (AIDS). But some National Institutes of Health (NIH) officials predict that it will be at least 2 more years before full-scale vaccine trials are in progress. For now, these two vaccines will be tested in five US centers—Johns Hopkins University Center for Immunization, Baltimore, Md; St Louis (Mo) University School of Medicine; University of Rochester (NY) Medical Center; Vanderbilt University Medical Center, Nashville, Tenn; and the University of Washington School of Medicine, Seattle. <h3>Pass Safety Tests</h3> The two vaccines have undergone safety testing previously. They did not appear to produce unwanted side effects. The trials are double-blinded and placebo-controlled. They will test the ability of
Short (And Shorter) Courses of Zidovudine
Authors: Kenneth McIntosh
Journal: New England Journal of Medicine (1998)

In this issue of the Journal, Wade and colleagues1 present data on the outcomes of short, prophylactic courses of zidovudine administered to infants born to women infected with the human immunodeficiency virus (HIV) who presented for obstetrical care in New York State between 1995 and 1997. Their report contains some reassuring and confirmatory information, as well as some surprising and provocative new observations. The pathophysiologic and therapeutic basis for the study involves both the timing of the vertical transmission of HIV and the prophylactic role of zidovudine in this setting.One of the earliest clues to the timing of mother-to-infant . . .
Changes in left ventricular filling and left atrial function six months after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy
Authors: Sherif F Nagueh, Nasser M Lakkis, Katherine J Middleton, Donna Killip, William A Zoghbi, Miguel A Quiñones, William H Spencer
Journal: Journal of the American College of Cardiology (1999)
Selling tobacco to children.
Authors: J S Mindell, D L Cohen
Journal: BMJ (1991)

pathy ... lest the term delude us into thinking that we understand what is going on."If increased capillary pressure is essential for red cell extravasation then it is possible that altered blood rheology is involved.During strenuous exercise stiffening of red cells induced by catecholamine occurs, and changed renal function results in high molecular weight proteinuria'°and haematuria4 in healthy subjects.It should be noted that IgA nephropathy is associated with both a high incidence of haematuria and altered blood rheology. 10here are several published claims that phase contrast microscopy of urinary sediment can dis- tinguish cells of "glomerular" origin from those of "non-glomerular" origin, but a study of the effects on the shape of red cells when normal blood was mixed with normal and pathological urine (Simpson, unpublished data) showed that glomerular type red cells were present at two minutes and persisted for 90 minutes.Small percentages of non-glomerular cells persisted throughout the study.Thus it seems that glomerular red cells are a response to the urinary environment.Although there may be good clinical reasons for measuring the red cell content of haematuric urine, it may be more diagnostically rewarding to determine whether or not there is an associated haemorrheological abnormality.
A PHYSICIAN'S CREED, PAST AND PRESENT, AS TO THE PHYSIOLOGY OF THE HEART.
Authors: WESLEY MILLS
Journal: JAMA (1907)

When honored by the American Medical Association with an invitation to become its guest and to contribute to its program, I cast about to consider in what way I could be of most use to those who might do me the further honor to read my paper when published. In my opinion, physiologists and physicians have stood too much apart. Although the American Physiological Society has held meetings for a great many years in the different great centers of the country, but few physicians ever attend those meetings or even read the reports of the papers presented, probably because they are usually published in periodicals other than medical. In most instances teachers of physiology to-day are not men in active medical practice, while many never were doctors, except academically. This has its advantages, but also some disadvantages. Physiology as such, even yet, it is to be feared, is only occasionally
The Effects of Bicarbonate on Blood Coagulation
Authors: Dennis W. Wong
Journal: JAMA (1980)

The anticoagulant effects of sodium and potassium bicarbonate were investigated with use of fresh human whole blood obtained from normal healthy volunteers. Results from prothrombin and thrombin clotting time determinations demonstrated that bicarbonate can interfere with the clotting process. Clinical data obtained from patients who received intravenous administration of sodium bicarbonate supported these findings. (<i>JAMA</i>244:61-62, 1980)
Observations on CHRONIC SPLENOMEGALY IN CHILDHOOD: DIAGNOSIS AND TREATMENT
Authors: R. Hutchison
Journal: BMJ (1928)

BEFORE proceedinig to the differen-tial diagnosis of the various splenomegalies of childhood, it is advisable to make sure that the abdominal tumour in questioni really is an enlarged spleen.Usually this is easy enouglh, but sometimes onie is in doubt, especially as to the possibility that the tumiour may be an enlarged left kidney or suprarenal.
Traditional and patient-centred outcomes with three classes of asthma medication
Authors: C. R. Jenkins
Journal: European Respiratory Journal (2005)

Lung function is commonly used as the primary endpoint in asthma clinical trials, but it may not reflect changes which are important to patients. The present study compared changes in, and relationships between, traditional and patient-centred end-points during treatment with three classes of asthma medication. Subjects with mild-to-moderate asthma were randomised to double-blind, double-dummy crossover treatment with eformoterol 12 µg <i>b.i.d.</i> or montelukast 10 mg <i>q.d.</i>, then single-blind treatment with fluticasone 250 µg <i>b.i.d.</i>/placebo capsules, with 6-week treatment periods and 1-week washouts. Individual “traditional” end-points (symptoms, reliever use, forced expiratory volume in one second per cent predicted, morning peak expiratory flow, airway hyperresponsiveness) and “patient-centred” end-points (asthma control questionnaire, quality of life, patient global assessments) were assessed. Principal component analysis and linear modelling were used to explore overall rank orders for treatment, and relationships between outcomes. A total of 58 subjects were randomised. The rank order of benefit from eformoterol and fluticasone differed for three factors derived from principal component analysis (eformoterol&gt;fluticasone for symptom/reliever use factor, fluticasone&gt;eformoterol for lung function factor, eformoterol = fluticasone for patient-centred factor). Montelukast was ranked third for all three factors. A significant relationship between patient-based variables and lung function was found only for montelukast treatment. In asthma treatment, traditional end-points do not fully capture patient-centred benefits, and the relationship between end-points differs with medication class.
More Exercise, Less Central Fat Distribution in Women
Authors: Ailsa Goulding
Journal: JAMA (1996)

<h3>To the Editor.</h3> —Reducing central fat distribution is a desirable health goal today. There is increasing evidence that women with a high proportion of their body fat in the trunk (indicating high intra-abdominal fat stores) have a higher risk of cardiovascular disease and diabetes<sup>1,2</sup>than those with proportionally more fat in the hips and thighs. We report that women who have high levels of physical activity maintain not only a lower body fat content and a higher lean body mass, but also have a more healthy regional fat distribution than women of similar height and weight who exercise less. We performed a cross-sectional observational study using dual-energy x-ray absorptiometry (DEXA) to compare the body composition and regional body fat distribution of competitive female athletes (n=14) habitually undertaking high levels of physical activity with values in sedentary women (n=14) matched for height and age. The DEXA measurements enable accurate determination