tbuckley/cabot-search huggingface dataset:
Historical evidence for the genetic heterogeneity of pseudoxanthoma elasticum
Authors: F.M. POPE
Journal: British Journal of Dermatology (2006)

Journal Article Historical evidence for the genetic heterogeneity of pseudoxanthoma elasticum Get access F.M. POPE F.M. POPE Institute of Dermatology, St John's Hospital for Diseases of the Skin, Lisle Street, Leicester Square, London WC2H 7BJ Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 92, Issue 5, 1 May 1975, Pages 493–509, https://doi.org/10.1111/j.1365-2133.1975.tb03117.x Published: 01 May 1975 Article history Accepted: 04 February 1974 Published: 01 May 1975
Behavioral Medicine Programs in Teaching Hospitals
Authors: Mary Gutmann, Rob Sanson-Fisher, Bruce Christiansen, Barry Blackwell
Journal: Psychotherapy and Psychosomatics (1987)

Behavioral medicine is a relatively new interdisciplinary field which combines biomedical and behavioral science knowledge, and applies them to prevention, diagnosis, treatment and rehabilitation. Behavioral medicine programs provide a valuable service to patients with chronic illness, psychosomatic or functional disorders, treatment noncompliance, and behavioral risk factors. Behavioral medicine faculty are also active in teaching and research on patient behavior, interviewing skills, health promotion and counseling, and management of chronic illnesses. However, the survival of behavioral medicine programs in teaching hospitals depends on their economic viability and academic status. Positive action is needed to ensure their continued growth and development.
1084 CYCLIN El AND Dl CAN DRIVE LIVER REGENERATION IN MICE WITHOUT CDK2
Authors: W. Hu, Y.A. Nevzorova, J.R. Nowak, U. Haas, N. Moro, Y. Geng, P. Sicinski, M. Barbacid, C. Trautwein, C. Liedtke
Journal: Journal of Hepatology (2011)
Guns of Tedium
Authors: Henry R. Viets
Journal: JAMA (1965)

To the Editor:—  When I read the editorial The Guns of Tedium, (JAMA191:935-936 [March 15] 1965), I was reminded of a dictum of long ago by an old experienced hand in editing medical papers: Whenever you see the word 'that,' cross it out and all the words preceding it.
Lung Function: Assessment and Application in Medicine
Authors: Jerry G. Greene
Journal: JAMA (1976)

The third edition of Cotes' well-known text continues in the same format as previous editions. The first 14 chapters are valuable overviews of the different facets of pulmonary physiology and pathophysiology, as well as brief descriptions of the testing methods used to demonstrate functional abnormalities. There is, as well, a small section on selected basic laboratory equipment, as previously.  On the dust cover the publisher states that this book has been extensively revised. However, the total number of pages is essentially as in the second edition, and as one reads through the book, most pages read almost as in the previous edition. However, some portions have been rewritten and more current data entered.  The 15th and 16th chapters relate to lung function in disease. Of necessity, only brief detail could be presented; and since other current texts have detailed evaluations of physiologic abnormality in these situations, I believe the author
The role of stratum corneum and dermal microvascular perfusion in penetration and tissue levels of water-soluble drugs investigated by microdialysis
Authors: C.J. Morgan, A.G. Renwick, P.S. Friedmann
Journal: British Journal of Dermatology (2003)

Background Hydrophilic drugs are poorly absorbed when applied topically, due to low partitioning through the lipid matrix of the stratum corneum. Cutaneous blood flow rapidly clears the absorbed drug, which may result in low tissue levels. This is of importance for topically applied drugs whose site of action is within the epidermis or dermis. Dermal drug levels can be measured using cutaneous microdialysis, which is a means of continuously sampling substances from the dermal extracellular fluid. Objectives To measure the contribution of stratum corneum barrier and microvascular perfusion in determining dermal tissue levels of hydrophilic drugs (aciclovir and penciclovir) in vivo. Methods Studies were performed using microdialysis of the volar surface of the forearm of healthy volunteers (n = 55) over a 5‐h collection period. Stratum corneum was removed by tape stripping, and barrier disruption quantified by measurement of transepidermal water loss (TEWL); dermal microvascular perfusion was modulated by inclusion of noradrenaline in the microdialysis perfusate. Results With intact skin and normal cutaneous blood flow the concentration of penciclovir recovered was below assay threshold (0·05 ng mL−1). With noradrenaline‐induced local vasoconstriction, the area under the curve of drug absorbed through normal skin (± SEM) was 13·3 ± 2·9 ng mL−1 h(0−5) for penciclovir and 27·6 ± 10·6 ng mL−1 h(0−5) for aciclovir. Removal of the stratum corneum (to glistening) by tape stripping increased penciclovir absorption by 1300‐fold and aciclovir absorption by 440‐fold, confirming the stratum corneum as the major barrier to hydrophilic drug absorption. Sequential barrier disruption by tape stripping gave a close correlation between penciclovir concentration absorbed per hour and barrier disruption measured by TEWL (r2 = 0·9283). There was a 15·6‐fold difference in the recovery of penciclovir through barrier‐deficient skin with and without cutaneous blood flow. There was no relationship between fibre depth and amount of drug dialysed, which suggests free movement of antiviral drug on reaching the aqueous environment of the dermis. Conclusions This study defines for the first time the relationship between the degree of mechanical barrier impairment and drug absorption at the same anatomical site in humans, and the role of blood flow in drug clearance in vivo.
Heritability and Genetic Linkage of Plasma Natriuretic Peptide Levels
Authors: Thomas J. Wang, Martin G. Larson, Daniel Levy, Emelia J. Benjamin, Diane Corey, Eric P. Leip, Ramachandran S. Vasan
Journal: Circulation (2003)

Natriuretic peptides play a critical role in the maintenance of salt and water homeostasis and regulation of vascular tone. Thus, interindividual variation in plasma natriuretic peptide levels may contribute to variation in susceptibility to volume overload and hypertension. It is unknown to what extent genetic factors contribute to variation in plasma natriuretic peptide levels.We studied 1914 Framingham Study participants (mean age 57 years, 53% women) who underwent routine echocardiography and testing for plasma N-terminal proatrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP). We estimated sex-specific multivariable models and used variance-components methods, implemented in SOLAR (Sequential Oligogenic Linkage Analysis Routines), to estimate heritability. Multipoint linkage analyses were performed using data from a 10-cM-density genome scan. Age, clinical, and echocardiographic variables accounted for 42% and 40% of the variation in log N-ANP and log BNP levels, respectively, in men. Corresponding values in women were 27% and 21%. Multivariable-adjusted heritabilities were 0.44 for log N-ANP and 0.35 for log BNP (P<0.0001). Genome-wide linkage analyses, based on 1142 participants from the 314 largest families, revealed 2 regions of suggestive linkage for log N-ANP and log BNP on chromosomes 2p25 (log-of-odds score 2.40) and 12p13 (log-of-odds score 2.13), respectively.In this community-based sample, a substantial proportion of the unexplained variation in plasma natriuretic peptide levels was attributable to additive genetic effects. Additional studies using candidate gene approaches may provide insight into the genetic loci that regulate plasma natriuretic peptide levels in humans.
Effects of Combination Lipid Therapy in the Management of Patients With Type 2 Diabetes Mellitus in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial
Authors: Andrew M. Tonkin, Lei Chen
Journal: Circulation (2010)

T he evidence base demonstrating that statins reduce major events, including in people with diabetes mellitus, 1 is arguably as robust as for any cardiovascular therapy.However, many individuals still experience end points despite the use of statins (the Figure).This "residual risk," which is much higher in people with coexistent cardiovascular disease, is probably most appropriately expressed in absolute terms, acknowledging the development of atherosclerosis over decades rather than the duration of trials and its multifactorial causation.However, the residual risk provides the rationale for testing other lipid-modifying therapies in combination with statins.People with diabetes mellitus have both qualitative and quantitative lipid changes.They include increased levels of triglycerides, small dense low-density lipoprotein (LDL) particles, and apolipoprotein B, as well as a decrease in levels of high-density lipoprotein (HDL) cholesterol.Fibrates, which are peroxisome proliferator receptor-␣ agonists, not only reduce triglyceride levels and possibly LDL cholesterol and chylomicron remnants and elevate HDL cholesterol but also are anti-inflammatory.The major beneficial effect of statins is to decrease LDL cholesterol.However, lower levels of HDL cholesterol and possibly increasing levels of triglycerides still denote elevated risk in those taking statins, 2,3 even when LDL cholesterol levels are very low, 2 and particularly in those with diabetes mellitus.
S78 Determinants of macrophage responses to Streptococcus pneumoniae
Authors: G. S. Tomlinson, S. Khandavilli, J. Cohen, C. Hyams, J. Brown, M. Noursadeghi
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> <i>Streptococcus pneumoniae</i> is the commonest cause of pneumonia and associated with marked inflammatory responses that underpin its immunopathogenesis. Surprisingly little is known about the molecular determinants of host–pathogen interactions that mediate these responses. We have studied the role of the pneumococcal capsule and surface lipoproteins in innate immune responses by macrophages that comprise the first line of cellular immune defence within the lung. <h3>Methods</h3> Human macrophage responses to wild type <i>S pneumoniae</i> (TIGR4) and isogenic mutant strains deficient in capsule (P1672) or surface lipoproteins (Δlgt) were investigated at the level of intracellular signalling, genome-wide transcriptional profiling and at protein level by cytokine ELISA. <h3>Results</h3> Unencapsulated bacteria invoked greater activation of the classical NFkB pathway, suggesting that the capsule may serve to inhibit some innate immune host pathogen interactions. In contrast, the Δlgt strain showed attenuated activation of NFkB, suggesting that lipoproteins are important ligands for innate immune recognition of pneumococci. Transcriptional responses to both unencapsulated and Δlgt strains showed marked differences to wild type pneumococci. However, quantitatively, major gene expression changes were preserved in the mutant strains. Despite the divergent effects on NFkB activation, both unencapsulated and Δlgt strains showed attenuated responses amongst these genes, although some key responses such as upregulation of TNFα were equivalent in all strains. Transcription factor enrichment analysis was conducted for the list of genes up-regulated by each strain to obtain new insight into the different pathways by which pneumococci may activate inflammatory responses. As expected, genes up-regulated by the wild type strain were enriched only for the NFkB family. In keeping with the signalling data, the Δlgt strain was not enriched for NFkB but only the PPARγ-RXR transactivator, and the unencapsulated strain was highly enriched for NFkB and a raft of other transcription factors. <h3>Conclusion</h3> Pneumococcal capsule and lipoproteins are important determinants of inflammatory responses to pneumococci. Our data suggest that the capsule inhibits multiple innate immune signalling pathways and that lipoproteins are critically important for activation of the canonical NFkB pathway. TNFα responses are independent of capsule and lipoproteins.
Returning doctors to medicine
Authors: M. Baker, G. Batstone, S. Kisely
Journal: BMJ (1998)

Just as economies go through cycles of ‘boom and bust', in the medical world we seem to have either too many doctors or too few. Not so long ago, there were dire threats of medical unemployment.(1) Nowadays there are dire threats of not having enough doctors to meet the healthcare demands of the near future.(2) Without being alarmist, the report of the Medical Workforce Standing Advisory Committee (MWSAC) points out the gap between demand for medical services and the available supply of doctors and, amongst other recommendations, calls for improved measures to retain doctors in the medical workforce.

All medical disciplines are likely to feel some effects of a deficit in the supply of doctors, but problems will be most obvious in those fields such as psychiatry and anaesthetics where it is already hard to recruit consultants. Until the proposed change in medical student numbers is manifest as specialists and general practitioners, the situation is likely to remain critical. Further, it can be difficult to gauge accurately demand between differing specialties. This can result in large swings in the number of specialist registrars. Disciplines like obstetrics and gynaecology have gone from under to oversupply within a short time frame.

With the increase in the proportion of female graduates in medicine, the number of doctors taking career breaks will increase. If these breaks are prolonged, then there is a risk of losing good doctors unless some way of re-introducing them into clinical practice is found. In the last …
Cryogel Micromechanics Unraveled by Atomic Force Microscopy‐Based Nanoindentation
Authors: Petra B. Welzel, Jens Friedrichs, Milauscha Grimmer, Steffen Vogler, Uwe Freudenberg, Carsten Werner
Journal: Advanced Healthcare Materials (2014)

Cell‐instructive physical characteristics of macroporous scaffolds, developed for tissue engineering applications, often remain difficult to assess. Here, an atomic force microscopy‐based nanoindentation approach is adapted to quantify the local mechanical properties of biohybrid glycosaminoglycan–poly(ethylene glycol) cryogels. Resulting from cryoconcentration effects upon gel formation, cryogel struts are observed to feature a higher stiffness compared to the corresponding bulk hydrogel materials. Local Young's moduli, porosity, and integral moduli of the cryogel scaffolds are compared in dependence on gel formation parameters. The results provide valuable insights into the cryogelation process and a base for adjusting physical characteristics of the obtained cryogel scaffolds, which can critically influence the cellular response.
Why Physicians Should Not Lie for Their Patients
Authors: Robert M. Sade
Journal: The American Journal of Bioethics (2012)

Click to increase image sizeClick to decrease image size Acknowledgments This publication was supported by the South Carolina Clinical & Translational Research Institute, Medical University of South Carolina's Clinical and Translational Science Award number UL1RR029882. The contents are solely the responsibility of the author and do not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
Small bowel gas in severe ulcerative colitis.
Authors: C N Chew, D J Nolan, D P Jewell
Journal: Gut (1991)

The prognostic significance of excess small bowel gas on a plain abdominal radiograph has been assessed in 75 patients with severe attacks of ulcerative colitis requiring intravenous hydrocortisone. The radiographs were reviewed without knowledge of the subsequent outcome. Small bowel distension was defined as the presence of three or more loops of gas filled small bowel. Forty two patients responded to medical treatment and 33 underwent colectomy. The two groups were comparable for age, sex, and length of history. The surgical group had more extensive disease. Of those who did well on medical therapy, 18 (42.9%) had small bowel distension compared with 24 of 33 (72.7%) who failed medical therapy. The difference was significant (p less than 0.05, odds ratio = 3.55, 95% confidence interval of 2.27-5.87). Of the 24 patients with small bowel distension who came to surgery, five had more than four loops of gas filled small bowel. This degree of distension was not seen in any of the patients settling on medical therapy. Thus the presence of small bowel distension on a plain abdominal radiograph in a patient with severe ulcerative colitis may predict a poor response to medical therapy.
Transcriptome sequencing, microarray, and proteomic analyses reveal cellular and metabolic impact of hepatitis C virus infection in vitro†‡§
Authors: Stephen D. Woodhouse, Ramamurthy Narayan, Sally Latham, Sheena Lee, Robin Antrobus, Bevin Gangadharan, Shujun Luo, Gary P. Schroth, Paul Klenerman, Nicole Zitzmann
Journal: Hepatology (2010)

Hepatitis C virus (HCV) is a major cause of liver disease but the full impact of HCV infection on the hepatocyte is poorly understood. RNA sequencing (RNA-Seq) is a novel method to analyze the full transcriptional activity of a cell or tissue, thus allowing new insight into the impact of HCV infection. We conducted the first full-genome RNA-Seq analysis in a host cell to analyze infected and noninfected cells, and compared this to microarray and proteomic analyses. The combined power of the triple approach revealed that HCV infection affects a number of previously unreported canonical pathways and biological functions, including pregnane X receptor/retinoic acid receptor activation as a potential host antiviral response, and integrin-linked kinase signaling as an entry factor. This approach also identified several mechanisms implicated in HCV pathogenesis, including an increase in reactive oxygen species. HCV infection had a broad effect on cellular metabolism, leading to increases in cellular cholesterol and free fatty acid levels, associated with a profound and specific decrease in cellular glucose levels. Conclusion: RNA-Seq technology, especially when combined with established methods, demonstrated that HCV infection has potentially wide-ranging effects on cellular gene and protein expression. This in vitro study indicates a substantial metabolic impact of HCV infection and highlights new mechanisms of virus–host interaction which may be highly relevant to pathogenesis in vivo. Hepatology 2010
Long term smoking contributes to cognitive decline
Authors: Roger Dobson
Journal: BMJ (2004)

Researchers have found that among people who had their IQ measured at the age of 11, smokers had the greater cognitive decline by the age of 64. Smokers also had lower psychomotor speeds.

“We conclude that long term smoking does not produce long term cognitive benefits; to the contrary, smoking makes a small but significant contribution to cognitive decline from age 11 to 64.

“Current smokers and non-smokers had significantly different mental test scores at age 64. This difference remained after adjustment for …
Bortezomib-Mediated Inhibition of Steroid Receptor Coactivator-3 Degradation Leads to Activated Akt
Authors: Gustavo Ayala, Jun Yan, Rile Li, Yi Ding, Timothy C. Thompson, Martha P. Mims, Teresa G. Hayes, Vivian MacDonnell, R. Garret Lynch, Anna Frolov, Brian J. Miles, Thomas M. Wheeler, J. Wade Harper, Ming-Jer Tsai, Michael M. Ittmann, Dov Kadmon
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To assess the safety of administering bortezomib to patients undergoing a radical prostatectomy, to assess pathologic changes induced by bortezomib in prostate cancer specimen, and to verify alterations by the drug in proteasome protein targets. Experimental Design: Bortezomib is a proteasome inhibitor that has shown activity in vitro and in vivo in prostate cancer. We performed a neoadjuvant clinical trial of bortezomib in men with prostate cancer at high risk of recurrence. The primary endpoints were to evaluate safety and biological activity. Results: Bortezomib is generally safe in the preoperative setting. Antitumor activity was manifested by tumor cytopathic effect, drops in serum prostate-specific antigen in some patients, and increases in tumor apoptosis. This was associated with cytoplasmic entrapment of nuclear factor-κB. We found an unexpected increase in proliferation in treated tissues and in vitro. Bortezomib also increased SRC-3 levels and phosphorylated Akt, both in vitro and in treated prostate cancer tissues. Knockdown of SRC-3 blocked the increase in activated Akt in vitro. Combined treatment with bortezomib and the Akt inhibitor perifosine was more effective than either agent alone in vitro. Conclusion: These data suggest that combined therapies targeting the proteasome and the Akt pathway may have increased efficacy.
Health promotion in general practice. Simple education is never enough.
Authors: T A Sheldon, G D Smith, C Davison
Journal: BMJ (1993)

be fully funded and must therefore address only the most limited and primitive expectations of both the patients and the professionals.The persistent clinical poverty of most NHS general practice cannot be cured or palliated by bolting on such token luxuries as well person clinics.Unless the BMA finds the courage and imagination to insist on resources for a labour intensive rather than a technology intensive public service, aiming at comprehensive anticipatory care for our whole population, even the best practices will continue to report failure.
Does ST/T Wave Change on Resting ECG in Patients with Myocardial Bridging Indicate a Silent Ischemia or a Regional Myocardial Abnormality?
Authors: Mustafa Aparci, Murat Yalcin, Zekeriya Arslan, Zafer Isilak, Cengiz Ozturk, Namık Ozmen
Journal: Journal of the American College of Cardiology (2013)
Repeated Mycoplasma pneumoniae Pneumonia After 4 1/2 Years
Authors: Hjordis M. Foy
Journal: JAMA (1971)

A recurrence of Mycoplasma pneumoniae pneumonia after 4 1/2 years was observed in a 40-year-old housewife. Both infections were documented by isolation of the organism, fourfold antibody rise, and pulmonary infiltrate. Naturally acquired immunity to M pneumoniae infection may not always be long lasting.
A complex bilateral polysyndactyly disease locus maps to chromosome 7q36
Authors: Olga Tsukurov, Annemie Boehmer, Jack Flynn, Jean-Philippe Nicolai, Ben C. J. Hamel, Saskia Traill, David Zaleske, Henry J. Mankin, Howard Yeon, Chrystal Ho, Cliff Tabin, J. G. Seidman, Christine Seidman
Journal: Nature Genetics (1994)