tbuckley/cabot-search huggingface dataset:
Asymmetric Dimethylarginine, C-Reactive Protein, and Carotid Intima-Media Thickness in End-Stage Renal Disease
Authors: Carmine Zoccali, Francesco Antonio Benedetto, Renke Maas, Francesca Mallamaci, Giovanni Tripepi, Lorenzo Salvatore Malatino, Rainer Bo[Combining Diaeresis]ger
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase that has been linked to endothelial dysfunction and atherosclerosis in the general population. ADMA is also elevated in end-stage renal disease and may contribute to the high cardiovascular risk in patients with chronic renal failure. A prospective cohort study was performed to investigate the relationship between plasma ADMA, C-reactive protein (CRP), and intima-media thickness (IMT) in 90 patients undergoing hemodialysis. In the baseline study, plasma ADMA was directly related to IMT both on univariate analysis (r = 0.32, P = 0.002) and on multiple regression analysis (β = 0.23, P = 0.01). In the follow-up study (15 mo) IMT changes were significantly related to ADMA (r = 0.51, P = 0.02) and serum CRP (r = 0.53, P = 0.01) in patients with initially normal IMT. In these patients, ADMA and CRP were strongly interrelated (r = 0.64, P = 0.002), and on multiple regression analysis the interaction between ADMA and CRP emerged as the sole independent predictor of the progression of intimal lesions. Independently of other risk factors, plasma ADMA in patients on hemodialysis is significantly related to IMT. Furthermore, in patients with initially normal IMT, ADMA and CRP are interacting factors in the progression of carotid intimal lesions. These data support the hypothesis that accumulation of this endogenous inhibitor of NO synthase is an important risk factor for cardiovascular disease in chronic renal failure and suggest a possible link between ADMA and inflammation.
Effects of Exercise and Nutrition on Memory in Japanese Americans With Impaired Glucose Tolerance
Authors: G. Stennis Watson, Mark A. Reger, Laura D. Baker, Marguerite J. McNeely, Wilfred Y. Fujimoto, Steven E. Kahn, Edward J. Boyko, Donna L. Leonetti, Suzanne Craft
Journal: Diabetes Care (2006)

Type 2 diabetes, impaired glucose tolerance (IGT), and associated hyperinsulinemia increase the risk for impaired verbal memory (1–3). In rodents, insulin resistance adversely affects brain structures that support memory (4). In humans, pharmacologic management of diabetes improves cognitive functioning (5,6). Weight loss and exercise decrease the incidence of diabetes (7,8). This study examined whether endurance exercise and dietary fat restriction would improve cognition in Japanese American adults who have a high risk for IGT and type 2 diabetes (9).

Adults with IGT were recruited from the Japanese American Community Diabetes Study. Screening and diagnostic procedures have been described previously (10). Participants (15 active and 13 control) completed cognitive testing at baseline and at 6 and 12 months. Treatment was randomly assigned, and groups were equivalent with respect to baseline age ([mean ± SD] active 58.0 ± 9.7 and control 60.6 ± 9.0 years), BMI (active 24.7 ± 3.2 and control 26.7 ± 4.3 kg/m2), V o2max (active 29.5 ± 7.1 and control 27.4 ± 5.6 ml · kg−1 · min−1), and 2-h oral glucose tolerance test (OGTT) glucose levels (active 9.4 ± 1.1 and control 9.4 ± 0.9 mmol/l).

Active participants followed an American Heart Association step 2 eucaloric diet (total calories <30% fat, <7% saturated fat, 55% carbohydrate, and 15% protein). An exercise physiologist supervised walking or jogging on a treadmill three times weekly for 1 h. …
DNA Double-Strand Break Repair Genes and Oxidative Damage in Brain Metastasis of Breast Cancer
Authors: Stephan Woditschka, Lynda Evans, Renata Duchnowska, L. Tiffany Reed, Diane Palmieri, Yongzhen Qian, Sunil Badve, George Sledge, Brunilde Gril, Mirit I. Aladjem, Haiqing Fu, Natasha M. Flores, Yesim Gökmen-Polar, Wojciech Biernat, Ewa Szutowicz-Zielińska, Tomasz Mandat, Tomasz Trojanowski, Waldemar Och, Bogumiła Czartoryska-Arlukowicz, Jacek Jassem, James B. Mitchell, Patricia S. Steeg
Journal: JNCI Journal of the National Cancer Institute (2014)

Breast cancer frequently metastasizes to the brain, colonizing a neuro-inflammatory microenvironment. The molecular pathways facilitating this colonization remain poorly understood.Expression profiling of 23 matched sets of human resected brain metastases and primary breast tumors by two-sided paired t test was performed to identify brain metastasis-specific genes. The implicated DNA repair genes BARD1 and RAD51 were modulated in human (MDA-MB-231-BR) and murine (4T1-BR) brain-tropic breast cancer cell lines by lentiviral transduction of cDNA or short hairpin RNA (shRNA) coding sequences. Their functional contribution to brain metastasis development was evaluated in mouse xenograft models (n = 10 mice per group).Human brain metastases overexpressed BARD1 and RAD51 compared with either matched primary tumors (1.74-fold, P < .001; 1.46-fold, P < .001, respectively) or unlinked systemic metastases (1.49-fold, P = .01; 1.44-fold, P = .008, respectively). Overexpression of either gene in MDA-MB-231-BR cells increased brain metastases by threefold to fourfold after intracardiac injections, but not lung metastases upon tail-vein injections. In 4T1-BR cells, shRNA-mediated RAD51 knockdown reduced brain metastases by 2.5-fold without affecting lung metastasis development. In vitro, BARD1- and RAD51-overexpressing cells showed reduced genomic instability but only exhibited growth and colonization phenotypes upon DNA damage induction. Reactive oxygen species were present in tumor cells and elevated in the metastatic neuro-inflammatory microenvironment and could provide an endogenous source of genotoxic stress. Tempol, a brain-permeable oxygen radical scavenger suppressed brain metastasis promotion induced by BARD1 and RAD51 overexpression.BARD1 and RAD51 are frequently overexpressed in brain metastases from breast cancer and may constitute a mechanism to overcome reactive oxygen species-mediated genotoxic stress in the metastatic brain.
Cost effectiveness of a new strategy to identify HNPCC patients
Authors: W Kievit, J H F M de Bruin, E M M Adang, J L Severens, J H Kleibeuker, R H Sijmons, T J Ruers, F M Nagengast, H F A Vasen, J H J M van Krieken, M J L Ligtenberg, N Hoogerbrugge
Journal: Gut (2004)

<b>Background:</b> Distinguishing hereditary non-polyposis colorectal cancer (HNPCC) from non-hereditary colorectal cancer (CRC) can increase the life expectancy of HNPCC patients and their close relatives. <b>Aim:</b> To determine the effectiveness, efficiency, and feasibility of a new strategy for the detection of HNPCC, using simple criteria for microsatellite instability (MSI) analysis of newly detected tumours that can be applied by pathologists. Criteria for MSI analysis are: (1) CRC before age 50 years; (2) second CRC; (3) CRC and HNPCC associated cancer; or (4) adenoma before age 40 years. <b>Methods:</b> The efficacy and cost effectiveness of the new strategy was evaluated against current practice. Decision analytic models were constructed to estimate the number of extra HNPCC mutation carriers and the costs of this strategy. The incremental costs and gain in life expectancy for a HNPCC mutation carrier were evaluated by Markov modelling. Feasibility was explored in five hospitals. <b>Results:</b> Using the new strategy, 2.2 times more HNPCC patients can be identified among a CRC population compared with current practice. This new strategy was found to be cost effective with an expected cost effectiveness ratio of €3801 per life year gained. When including the group of siblings and children, the cost effectiveness ratio became €2184 per life year gained. Sensitivity analysis showed these findings to be robust. <b>Conclusions:</b> MSI testing in a selection of newly diagnosed CRC patients was shown to be cost effective and a feasible method to identify patients at risk for HNPCC who are not recognised by family history.
Localization of neutral endopeptidase (NEP) mRNA in human bronchi
Authors: JN Baraniuk, K Ohkubo, OJ Kwon, J Mak, M Ali, R Davies, C Twort, M Kaliner, M Letarte, PJ Barnes
Journal: European Respiratory Journal (1995)

Neutral endopeptidase (NEP) may regulate peptide-induced inflammation in the respiratory tract. It is of interest to determine which respiratory resident cells express NEP. Trachea and bronchi from seven nonsmoking, nonasthmatic subjects were examined. NEP messenger ribonucleic acid (mRNA) was characterized by Northern blot hybridization of cultured human tracheobronchial epithelial and smooth muscle cells, and reverse transcriptase-polymerase chain reaction (RT-PCR) in trachea and bronchi. In situ hybridization with biotin- and 35S-labelled antisense complementary ribonucleic acid (cRNA) probes was used to determine the distribution of NEP mRNA in human bronchial mucosa. NEP-immunoreactive material was detected using MEK10 murine monoclonal antibodies and the immunogold method with silver enhancement. NEP mRNA was 4.5 kb in size in the cultured human smooth muscle and epithelial cells by Northern blot analysis. No evidence was found by RT-PCR for truncated, alternatively spliced NEP mRNAs, such as del exon 16 or del exons 5-18 in human bronchus. NEP mRNA was detected by in situ hybridization in epithelial cells, submucosal glands, bronchial smooth muscle and endothelium. NEP-immunoreactive material was identified in the epithelium, submucosal glands, bronchial smooth muscle, and endothelium, demonstrating an excellent correlation between the distribution of NEP mRNA and the cell surface protein. NEP mRNA and immunoreactive material were excluded from epithelial goblet cell and submucosal gland mucous cell vacuoles. We conclude that the various sites of NEP protein and mRNA expression correlate with the locations of peptide receptors and NEP enzyme function, and are consistent with the hypothesis that NEP may regulate peptide-induced inflammation in human bronchi.
Tissue Macrophages Suppress Viral Replication and Prevent Severe Immunopathology in an Interferon-I-Dependent Manner in Mice
Authors: Philipp A. Lang, Mike Recher, Nadine Honke, Stefanie Scheu, Stephanie Borkens, Nicole Gailus, Caroline Krings, Andreas Meryk, Andreas Kulawik, Luisa Cervantes-Barragan, Nico Van Rooijen, Ulrich Kalinke, Burkhard Ludewig, Hans Hengartner, Nicola Harris, Dieter Häussinger, Pamela S. Ohashi, Rolf M. Zinkernagel, Karl S. Lang
Journal: Hepatology (2010)

The innate immune response plays an essential role in the prevention of early viral dissemination. We used the lymphocytic choriomeningitis virus model system to analyze the role of tissue macrophages/Kupffer cells in this process. Our findings demonstrated that Kupffer cells are essential for the efficient capture of infectious virus and for preventing viral replication. The latter process involved activation of Kupffer cells by interferon (IFN)-I and prevented viral spread to neighboring hepatocytes. In the absence of Kupffer cells, hepatocytes were not able to suppress virus replication, even in the presence of IFN-I, leading to prolonged viral replication and severe T cell-dependent immunopathology. Conclusion: Tissue-resident macrophages play a crucial role in early viral capture and represent the major liver cell type exhibiting responsiveness to IFN-I and providing control of viral replication. (Hepatology 2010)
Decompression Sickness, an Emerging Recreational Hazard
Authors: A. Warner Dewey
Journal: New England Journal of Medicine (1962)

Skin manifestations (the "itches"). Intermittent prickling and burning sensations in the skin are experienced fairly often by divers during the actual decompression from a dive and immediately thereafter. This occurs more frequently after deep dives and, for some reason, is experienced more commonly during and after "dry" decompression in decompression chambers and flights to high altitude than with decompression in the water. This may be a consequence of rapid skin cooling in the "dry" environment, whereas in water decompression any external temperature change is generally gradual and in the direction of warmth. Objective skin lesions tend to have a . . .
Pediatric Cardiology and Cardiovascular Surgery: 1950-2000
Authors: R. M. Freedom, J. Lock, J. T. Bricker
Journal: Circulation (2000)

For those caring for the patient with congenital heart disease, the last 50 years of the 20th century was witness to staggering advances in virtually all aspects of pediatric cardiovascular medicine and surgery. The first half of the 20th century was not dormant in this regard. Dr Maude Abbott of Montreal had published her wonderful atlas in 1936 under the auspices of the American Heart Association, a unique compilation of 1000 cases of congenital heart disease.1 Dr Helen Taussig of Baltimore had founded her cardiac clinic at Johns Hopkins and had begun in the 1930s to characterize the clinical and fluoroscopic findings of a wide variety of congenital heart malformations; this material matured into her 2-volume compendium on congenital heart disease published in 1960.2 Dr Robert E. Gross of the Children’s Hospital in Boston successfully ligated the patent arterial duct in 1938, and that signal accomplishment ushered in the era of surgery for congenital heart disease.3 On the basis of her clinical observations that some children with cyanotic congenital heart disease became progressively more cyanotic coincidently with closure of the arterial duct and cognizant of Gross’s benchmark contribution, Dr Taussig traveled to Boston to attempt to persuade him to construct an arterial duct. When he refused, she broached the subject to Dr Blalock at Johns Hopkins. Some years earlier, when in Vanderbilt and with the technical assistance of Vivien Thomas, in an attempt to produce pulmonary hypertension and using the dog as the experimental animal, Dr Blalock constructed an end-to-end surgical anastomosis between the subclavian artery and the pulmonary artery. With Dr Alfred Blalock as the surgeon and the wisdom of his assistant Vivien Thomas, Taussig and Blalock revolutionized the care of the cyanotic child with the construction of the subclavian artery–to–pulmonary artery end-to-side anastomosis, thus augmenting …
Diabetic Retinopathy Is Related to Both Endothelium-Dependent and -Independent Responses of Skin Microvascular Flow
Authors: Thanh T. Nguyen, Jonathan E. Shaw, Carol Robinson, Ryo Kawasaki, Jie Jin Wang, Andreas J. Kreis, Tien Y. Wong
Journal: Diabetes Care (2011)

OBJECTIVE Endothelial dysfunction has been hypothesized as a possible pathogenic factor in the development of diabetic retinopathy (DR). We examined the relationship of DR to endothelium-dependent and endothelium-independent responses in skin microvascular flow. RESEARCH DESIGN AND METHODS Participants consisted of 224 individuals with diabetes: 85 with type 1 diabetes and 139 with type 2 diabetes. Sodium nitroprusside (SNP) and acetylcholine (ACh) were delivered across the skin by iontophoresis. Laser Doppler flowmetry was used to assess the skin microcirculation response to SNP (endothelium-independent response) and ACh (endothelium-dependent response). The presence and severity of DR were graded from retinal photographs using a standard protocol. RESULTS Of 224 participants, 64.3% had DR. After multivariable adjustment, participants with reduced responses to SNP or ACh were more likely to have DR, with an odds ratio (OR) of 2.33 (95% CI 1.09–5.01) for SNP and 2.20 (1.05–4.61) for ACh, comparing participants with responses below and above the median values. Participants with reduced responses (below the median) to both SNP and ACh were nearly four times more likely to have DR (OR 3.86 [1.45–10.3]) than those with SNP and ACh both above the median values. CONCLUSIONS The presence of DR was associated with a reduction in skin microcirculation responses to iontophoresis of both SNP and ACh, suggesting that vascular processes associated with both endothelial dysfunction and endothelial function-independent mechanisms may be pathogenically related to DR.
Diagnosing Diabetic Foot Osteomyelitis in Patients Without Signs of Soft Tissue Infection by Coupling Hybrid 67Ga SPECT/CT With Bedside Percutaneous Bone Puncture
Authors: Elisabeth Aslangul, Jocelyne M’Bemba, Nadine Caillat-Vigneron, Sophie Coignard, Etienne Larger, Christian Boitard, Benjamin A. Lipsky
Journal: Diabetes Care (2013)

Successful treatment of osteomyelitis is more likely with accurate diagnosis and identification of the causative pathogens. This typically requires obtaining a specimen of bone, usually by image-guided biopsy. We sought to develop a simpler bedside method for definitively diagnosing osteomyelitis.Over 2 years, we enrolled consecutive patients presenting to our diabetic foot clinic with a foot ulcer and clinically suspected osteomyelitis but without soft tissue infection. Each underwent hybrid (67)Ga single-photon emission computed tomography and X-ray computed tomography (SPECT/CT) imaging; those with a positive scan underwent bedside percutaneous bone puncture. Patients with a positive bone culture received culture-guided antibiotic therapy. Patients with negative (67)Ga SPECT/CT imaging or with positive imaging but negative bone culture were not treated with antibiotics. All patients were followed up for ≥ 1 year.Among 55 patients who underwent (67)Ga SPECT/CT imaging, 13 had negative results and all of their foot ulcers resolved without antibiotic therapy. Among 42 with positive imaging, 2 were excluded (for recent antibiotic therapy) and 40 had bone punctures (3 punctured twice): 19 had negative results, 3 of which were likely false negatives, and 24 had positive results (all gram-positive cocci). At follow-up, 3 patients had died, 3 had undergone amputation, and 47 had no evidence of foot infection. The sensitivity and specificity of this combined method were 88.0 and 93.6%, respectively, and the positive and negative predictive values were 91.7 and 90.7%, respectively.Coupling of (67)Ga SPECT/CT imaging and bedside percutaneous bone puncture appears to be accurate and safe for diagnosing diabetic foot osteomyelitis in patients without signs of soft tissue infection, obviating the need for antibiotic treatment in 55% of suspected cases.
Safety at Scene—A Manual for Paramedics and Immediate Care Doctors
Authors: Eddie Chaloner
Journal: Journal of the Royal Society of Medicine (2002)

I wish this excellent little book had been in print when I was working on the Helicopter Emergency Medical Service some six years ago. It might have spared me the minor embarrassment of nearly being electrocuted by the live rail while attending an incident where a woman had thrown herself under a tube train. Vic Calland's book contains a wealth of background information about the technical aspects of accident scenes of a kind that is difficult to acquire except through personal experience. He is to be congratulated for distilling his expertise into a readable and informative text.

Most doctors practise within the safe environment of the surgery or hospital. Within this setting we are accustomed to being ‘team leaders’, to making the critical decisions on priority and management, and to being in control. Outside hospital the position is very different. Accidents by their very nature present dangers to emergency service personnel, as re-emphasized by the deaths of many New York firefighters and policemen when the World Trade Center towers collapsed. In the early stages of a major incident or even a medium-size road traffic accident, chaos reigns. In such circumstances, ‘first responders’ must be constantly aware of the risks to their own safety and avoid becoming casualties themselves. The rapid re-establishment of control is the key to a successful outcome. Within this framework, doctors are not team leaders but team members who come under the control of other emergency services, usually the police or fire services. An understanding of this principle and an acceptance of an initially subordinate role of the medical services is crucial to the smooth and safe management of an accident scene.

In keeping with the frequency of road traffic accidents in the UK, about half the book is devoted to incident management, vehicle safety, casualty extraction and risks of hazardous substances at the accident scene. The remainder of the text contains much valuable technical information on specific scenarios, such as chemical and radiation hazards, the basics of aircraft, rail and underground safety and even hostage situations. Having been written before autumn 2001, the section on biological agents does not cover the now feared microbes such as anthrax, plague and smallpox, but we can hardly expect the author to be clairvoyant. That said, the section on chemical decontamination procedures is comprehensive and applies equally to biological threats.

My only criticism concerns the lack of a chapter on the effects of bomb blasts—familiar to many in Northern Ireland and, to a lesser extent, to the emergency services of London and other major cities in the UK. In view of recent events, this is an area of practice we may all need to revise.

This concise and easy-to-read text is sensibly fitted with a laminated cover to protect against stains from coffee, blood and oil, all familiar to the immediate care practitioner. I recommend it to anybody with an interest in prehospital medicine.
Similar Rates but Different Modes of Sequence Evolution in Introns and at Exonic Silent Sites in Rodents: Evidence for Selectively Driven Codon Usage
Authors: Jean-Vincent Chamary, Laurence D. Hurst
Journal: Molecular Biology and Evolution (2004)

In mammals divergence at fourfold degenerate sites in codons (K(4)) and intronic sequence (K(i)) are both used to estimate the mutation rate, under the supposition that both evolve neutrally. Does it matter which of these we use? Using either class of sequence can be defended because (1) K(4) is the same as K(i) (at least in rodents) and (2) there is no selectively driven codon usage (hence no systematic selection on third sites). Here we re-examine these findings using 560 introns (for 136 genes) in the mouse-rat comparison, aligned by eye and using a new maximum likelihood protocol. We find that the rate of evolution at fourfold sites and at intronic sites is similar in magnitude, but only after eliminating putatively constrained sites from introns (first introns and sites flanking intron-exon junctions). Any approximate congruence between the two rates is not, however, owing to an underlying similarity in the mode of sequence evolution. Some dinucleotides are hypermutable and differently abundant in exons and introns (e.g., CpGs). More importantly, after controlling for relative abundance, all dinucleotides starting with A or T are more prevalent in mismatches in exons than in introns, whereas C-starting dinucleotides (except CG) are more common in introns. Although C content at intronic sites is lower than at flanking fourfold sites, G content is similar, demonstrating that there exists a strong strand-specific preference for C nucleotides that is unique to exons. Transcription-coupled mutational processes and biased gene conversion cannot explain this, as they should affect introns and flanking exons equally. Therefore, by elimination, we propose this to be strong evidence for selectively driven codon usage in mammals.