tbuckley/cabot-search huggingface dataset:
Influence of rs5065 Atrial Natriuretic Peptide Gene Variant on Coronary Artery Disease
Authors: Emanuele Barbato, Jozef Bartunek, Fabio Mangiacapra, Sebastiano Sciarretta, Rosita Stanzione, Leen Delrue, Maria Cotugno, Simona Marchitti, Guido Iaccarino, Giusy Sirico, Sara Di Castro, Anna Evangelista, Diether Lambrechts, Peter Sinnaeve, Bernard De Bruyne, Frans Van De Werf, Stefaan Janssens, Keith A.A. Fox, William Wijns, Massimo Volpe, Speranza Rubattu
Journal: Journal of the American College of Cardiology (2012)
Prenatal PCB exposure, the corpus callosum, and response inhibition.
Authors: Paul Stewart, Susan Fitzgerald, Jacqueline Reihman, Brooks Gump, Edward Lonky, Thomas Darvill, Jim Pagano, Peter Hauser
Journal: Environmental Health Perspectives (2003)

The present study reports the association between prenatal exposure to polychlorinated biphenyls (PCBs), the corpus callosum, and response inhibition in children who are 4.5 years old. Children (n = 189) enrolled in the Oswego study were tested using a continuous performance test. We measured (square millimeters) the splenium of the corpus callosum, a pathway implicated in the regulation of response inhibition, using magnetic resonance imaging. Results indicated a dose-dependent association between cord blood PCBs and errors of commission. Splenium size but not other brain areas predicted errors of commission (r(2) = 0.20), with smaller size associated with more errors of commission. There was an interaction between splenium size and PCB exposure. The smaller the splenium, the larger the association between PCBs and errors of commission. If the association between PCBs and response inhibition is indeed causal, then children with suboptimal development of the splenium are particularly vulnerable to these effects. These data await replication.
Non-surgical Retrieval of a Broken Segment of Steel Spring Guide from the Right Atrium and Inferior Vena Cava
Authors: JOHN THOMAS, BRUCE SINCLAIR-SMITH, DENNIS BLOOMFIELD, ASGHAR DAVACHI
Journal: Circulation (1964)

The recovery of a broken segment of a steel spring guide from the right atrium and inferior vena cava without surgical intervention has been reported. The ready accessibility of an adequate instrument for retrieval of such intravascular bodies is recommended. It is possible that such an instrument may be also designed for myocardial biopsy. The relative ease of breakage probably points to a defect in the guides and a re-evaluation of the design and manufacture seems to be indicated.
The renal tubulointerstitium in diabetes mellitus
Authors: Fuad N. Ziyadeh, Stanley Goldfarb
Journal: Kidney International (1991)

Renal injury in diabetes mellitus is an important clinical as well as biological problem. Approximately 30% of patients with type I or insulin-dependent diabetes mellitus [1] and 5 to 10% of patients with type II or non-insulin-dependent diabetes mellitus [2] will develop chronic renal insufficiency requiring treatment in an end-stage renal disease program. The mechanism of this injury, the underlying cause, and the nature of progressive renal insufficiency are unclear. In general, it has been proposed that diabetes is predominantly a glomerular disease as there is a progressive increase in urinary albumin excretion from 15 to 30 µg/min up to nephrotic range proteinuria over 5 to 12 years, followed by hypertension and decline in glomerular filtration rate (GFR) after a mean duration of 17 years of diabetes in the segment of patients at risk. The pathologic lesion of diffuse glomerular sclerosis or nodular intercapillary glomerular sclerosis is typically seen in biopsies from patients with advanced diabetic nephropathy [3, 4]. Moreover, Mauer and colleagues [5] and Osterby and Gunderson [6] have shown that there is a close correlation between the expansion of the glomerular mesangium and the declining filtration surface area, as well as the declining GFR in affected patients. These results support the view of diabetic nephropathy as a primary glomerular and perhaps primary mesangial disorder.  However, a number of contradictory observations suggest a potentially important role for alterations in non-glomerular structures which reside within the renal interstitium in the development of renal insufficiency in patients with diabetes mellitus. The following discussion will review the evidence for a role of altered structure and function of the renal tubulointerstitium in diabetes, and propose the hypotheses that altered tubular transport and metabolic activity contributes to proteinuria and altered renal hemodynamics in diabetes, and that interstitial fibrosis plays an important role in the ultimate expression of renal insufficiency in diabetic nephropathy. We will discuss several potential mechanisms for these functional and structural changes and suggest a central pathogenetic role for hyperglycemia  per se  in the induction of these abnormalities.
Organ donation. II-Logistical disincentives to organ donation.
Authors: N J Odom
Journal: BMJ (1990)

of fluids to reduce cerebral oedema will diminish cardiac output and renal blood flow.Kidney-The age limit for donation is around 70, provided the plasma urea and creatinine values were normal on admission and there is no history of renal disease or hypertension.Essential requirements for the kidneys are an adequate cardiac output and fluid input.Diuretics should not be needed unless to treat acute tubular injury due to an episode of hypotension.Pancreas-Donors under 50 are suitable provided there is no history of diabetes, pancreatitis, or alcohol abuse.9The pancreas is sensitive to ischaemic injury so a good cardiac output is very important.Liver-Donors under 50 are suitable if there is no history of liver disease, gall stones, or alcohol abuse.' Size matching is important so girth and weight measure- ments are needed by the transplant team.The liver is sensitive to ischaemic damage so donation is contraindicated if there has been prolonged resuscitation or a systolic blood pressure of less than 70 mm Hg for more than 30 minutes.Liver function tests should be performed.Heart-The age limit is about 50, but older hearts are more likely to be excluded on inspection because of unexpected atheroma." Size matching is liberal (±+ 20% in body weight under ideal circumstances).The heart should ideally be in sinus rhythm and must be able to sustain good peripheral perfusion and urine output with a low central venous pressure.Subendocardial infarction can occur when there is prolonged external cardiac massage or hypotension (criteria as for liver), and these normally preclude donation.If hypotension has occurred, cardiac enzyme measurement is useful to diagnose subendocardial infarction.Echocardiography may show unsuspected ventricular impairment.Principles of management are to optimise blood gases, fluids, and electrolytes and to avoid or minimise the use of inotropes, which deplete myocardial high energy phosphates.Ifdopamine is used for hypotension
Should HPV vaccine be given to men?
Authors: P. E Castle, I. Scarinci
Journal: BMJ (2009)

The best investment is to vaccinate preadolescent females, not males

On 9 September 2009, a US Food and Drug Administration (FDA) advisory panel recommended that the FDA approve Gardasil (Merck)—the quadrivalent human papillomavirus (HPV) vaccine against HPV types 6, 11, 16, and 18—for use in males aged 9-26 years to prevent genital warts (condyloma acuminata). The vaccine was 90% effective in preventing genital warts and reducing the incidence of persistent HPV 6 and HPV 11 anogenital infections1—which cause about 90% of genital warts in HPV niaive males—and 79% effective at reducing of the incidence of persistent anogenital HPV 16 infections and 96% of HPV 18 infections. Therefore, carriage in the male population of the two HPV genotypes that cause 70% of cervical cancer worldwide in women could be greatly reduced by widespread HPV vaccination. The question is should men be vaccinated?

In the linked study (doi:10.1136/bmj.b3884), Kim and Goldie report an independent analysis of the cost effectiveness of male HPV vaccination in the United States.2 They found that only under the most favorable assumptions for the benefits of adding male HPV vaccination to …
P136 Multidimensional prognostic index for exacerbations of COPD
Authors: PM Short, PA Williamson, A Singanayagam, A Akram, S Schembri, JD Chalmers
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Prognostic assessment of COPD exacerbations is currently limited by models that only take into account short term prognostic factors. We developed a multidimensional tool for COPD exacerbations, predicting both short and long term outcome. <h3>Methods</h3> A prospective multicentre, UK observational cohort of patients hospitalised with exacerbations of COPD 2009–2011. Cox-proportional hazards regression used to identify independent predictors of 30-day and 1 year mortality. Two independent risk scores based on exacerbation severity (acute score) and severity of COPD and co-morbidities (chronic score) were developed. The two scores were then used to generate a 4 class decision grid based on the GOLD 2011 criteria for stable COPD. <h3>Results</h3> 1343 patients were included. 749 patients were readmitted or died during 1 year follow-up. Predictors of 30-day mortality (acute score) were new onset confusion HR 2.23 (95%CI 1.34–3.71)- 1 point, Urea &gt;7mmol/L 2.64 (95%CI 1.51–4.61)- 1 point, acidosis 4.22 (95%CI 2.68–6.65)- 2 points, glucose &gt;8mmol/L 1.56 95%CI (1.00–2.46)- 1 point and albumin &lt;35g/L 2.23 (95%CI 1.42–3.5)- 1 point and heart rate &gt;110bpm 2.37 (95%CI 1.50–3.73)- 1 point. The AUC for 30 day mortality for the acute score was 0.84 (95%CI 0.80–0.88). The strongest predictors of 1 year mortality were age &gt;80 years HR 1.25 (95%CI 1.00–1.64)–1 point, neoplastic disease 1.91 (95%CI 1.37–2.65)–1 point, MRC dyspnoea grade 4 or 5 (3.82 95%CI 2.61–5.58)- 2 points, FEV<sub>1</sub> &lt;30% predicted 2.61 (95%CI 1.99–3.43)–1 point, long term oxygen therapy 1.60 95%CI 1.11–2.29)–1 point and a history of myocardial infarction or heart failure 2.76 95%CI 1.70–4.47)–1 point. The AUC for 1 year mortality of the chronic score was 0.76 (95%CI 0.73–0.80). The resulting 4 stage model identifies different outcomes within each subgroup (See Figure 1). Furthermore the 4 stage model predicted 30-day mortality AUC 0.76 (95%CI 0.72–0.79), 1 year mortality 0.72 (95%CI 0.70–0.74) and readmissions 0.74 (95%CI 0.72–0.76) better than GOLD 2011 criteria. <h3>Conclusion</h3> A multidimensional prognostic index can predict both short and long term outcomes after COPD exacerbations, and divides patients into clinically useful subgroups based on exacerbation severity and chronic health status.
Elevated liver enzyme tests among patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate and/or leflunomide
Authors: J R Curtis, T Beukelman, A Onofrei, S Cassell, J D Greenberg, A Kavanaugh, G Reed, V Strand, J M Kremer
Journal: Annals of the Rheumatic Diseases (2009)

Introduction: Potential hepatotoxicity associated with disease-modifying antirheumatic drugs (DMARDs) requires laboratory monitoring. In patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA), the incidence of elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST) enzymes associated with methotrexate (MTX), leflunomide (LEF) and MTX+LEF versus other DMARDs was examined. Methods: Patients with RA and PsA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) initiating DMARDs were identified. Abnormalities were identified when either was 1- or 2-fold times above the upper limits of normal (ULN). Odds ratios (OR) between MTX/LEF dose and elevated ALT/AST enzymes were estimated using generalised estimating equations. Interaction terms for use of MTX+LEF quantified the incremental risk of the combination compared with each individually. Results: Elevated ALT/AST levels (&gt;1× ULN) occurred in 22%, 17%, 31% and 14% of patients with RA receiving MTX, LEF, MTX+LEF or neither, respectively; elevations were 2.76-fold (95% CI 1.84 to 4.15) more likely in patients with PsA. Elevations &gt;2× ULN occurred in 1–2% of patients on MTX or LEF monotherapy compared with 5% with the combination. After multivariable adjustment and compared with either monotherapy, the combination of MTX and LEF was associated with a greater risk according to MTX dose used as part of the combination: MTX 10–17.5 mg/week, OR 2.91 (95% CI 1.23 to 6.90); MTX ⩾20 mg/week, OR 3.98 (95% CI 1.72 to 9.24). Conclusions: Abnormal ALT/AST levels developed in 14–35% of patients with RA or PsA initiating DMARD therapy. The risks were incrementally greater in those with PsA and in those receiving MTX (⩾10 mg/day) + LEF. These findings should help inform monitoring for potential hepatotoxicity in these patient populations.
Modulation of Ca2+ control of dog and rabbit cardiac myofibrils by Mg2+. Comparison with rabbit skeletal myofibrils.
Authors: R J Solaro, J S Shiner
Journal: Circulation Research (1976)

Increases in free Mg2+ from 0.04 to 10.0 mM with constant pH 7.0 TO 0.10 M ionic strength, and 2 mM MgATP2- caused a rightward shift of the free Ca-relative ATPase relation for both cardiac skeletal myofibrils. The specific activity of cardiac myofibrillar ATPase over a wide range of free Ca2+ was, however, depressed in 0.04 vs. 1.0 mM Mg2+, whereas a similar decrease in free Mg2+ slightly enhanced skeletal myofibrillar ATPase. Lowering free Mg2+ from 1.0 to 0.04 mM caused similar increases in cardiac and skeletal myofibrillar bound calcium, which were largely attributable to increased calcium binding to myofibrillar myosin. Raising free Mg2+ from 1.0 to 10.0 mM caused only a slight decrease of skeletal myofibrillar bound calcium, and this change was attributable to myofibrillar myosin. The same increase in free Mg2+ caused cardiac myofibrils to bind increased amounts of calcium and this change was not attributable to myofibrillar myosin. By subtracting calcium bound to myofibrillar myosin, we were able to estimate calcium binding by myofibrillar troponin. The transition between basal and maximal ATPase in 1.0 and 10 mM Mg2+ was found to be assocciated with binding of an additional 2 mol/mol of either skeletal or cardiac myofibrillar troponin.
Chronic Caregiving Stress Alters Peripheral Blood Immune Parameters: The Role of Age and Severity of Stress
Authors: Carmine M. Pariante, Bernardo Carpiniello, Germana Orrù, Rossella Sitzia, Alessandra Piras, Giulia Farci, Sergio Del Giacco, Giovanna Piludu, Andrew H. Miller
Journal: Psychotherapy and Psychosomatics (1997)

Background: To examine the impact of chronic psychological stress on the immune system, a series of cellular and humoral immunological parameters was compared in 18 female caregivers of handicapped people and 18 age- and sexmatched controls. Methods: The immunological parameters included assessment of T cell number (T cells, T helper, and T suppressor/cytotoxic) and function (delayed-type cutaneous hypersensitivity), antibody titers for latent herpesviruses (cytomegalovirus and herpes simplex virus 1 and 2), and markers of inflammation (complement C3 and C4 factors and c-reactive protein). Serum immunoglobulins (IgG, IgM, IgA, IgE) and titers for the nonlatent virus roseola were used to control for nonspecific elevations in serum proteins. Results were associated with the age of the investigated subjects, the severity of stress (family burden) and the degree of disability of the handicapped people. Results: Caregivers had a significantly lower percentage of T cells, a significantly higher percentage of T suppressor/cytotoxic cells and a significantly lower T helper:suppressor ratio. Subjects were also analyzed after division into two groups according to the median age (45 years). Compared to their matched controls, older caregivers (mean age = 50.3) also had lower numbers of T cells and T helper cells and higher antibody titers for cytomegalovirus. In addition, in the caregiver population severity of stress was significantly positively correlated with T suppressor/cytotoxic cells and negatively correlated with T helper:suppressor ratio. No other differences in the immune parameters were found between caregivers and controls. Conclusions: The results indicate that psychological stress differentially affects various aspects of the immune system and confirm the relevant role of age and severity of stress in modulating these influences.
Abstract LB-63: Expression of α+β+ splice variant of human telomerase reverse transcriptase (hTERT) in cytokeratin 19 (CK-19) positive circulating tumor cells (CTCs) of breast cancer patients
Authors: Kleo Parisi, Areti Strati, Nikolaos Malamos, Vassilis Georgoulias, Evi Lianidou
Journal: Cancer Research (2010)

Abstract Introduction: Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase. The α+β+ splice variant is the functional variant of hTERT. Circulating tumor cells (CTCs) have already been established as strong predictors of prognosis in patients with metastatic breast cancer. Our group has previously shown the prognostic significance of cytokeratin 19 (CK-19) mRNA-positive CTCs in early breast cancer. The aim of our study was to study the expression of hTERT α+β+ splice variant in CK-19 positive CTCs in breast cancer samples by qRT-PCR. Materials and Methods: Peripheral blood (20 ml in EDTA) was obtained from 25 patients with early breast cancer before the administration of adjuvant chemotherapy, 14 patients with verified metastasis who were all tested positive for CK-19 expression by real time PCR (Stathopoulou et al, Int J Cancer 2006), and 17 female healthy volunteers. CTCs were isolated after ficoll density gradient centrifugation, following enrichment with immunomagnetic Ber-EP4 coated capture beads, mRNA was isolated using oligo (dT)25 coated magnetic beads, followed by cDNA synthesis. The expression of hTERT α+β+ splice variant was tested in both CTCs and PBMCs fractions by quantitative real-time PCR in the LightCycler, (Mavroyiannou et al, Clin Chem, 2007). Results: hTERT α+β+ splice variant was expressed in 4/14 (29%) of CK-19 mRNA positive CTCs samples from patients with metastasis and in 5/24 (21%) of CK-19 mRNA positive CTCs samples from patients with early breast cancer. None of the 17 female healthy volunteers CTCs fraction was tested positive for hTERT α+β+ splice variant, while the corresponding PBMCs fraction was positive in all cases. Conclusions: To our knowledge this is the first report on the expression of hTERT α+β+ splice variant in CTCs of patients with early breast cancer and verified metastasis. Further studies are needed to evaluate and confirm our findings in a larger number of patients. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-63.
Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions
Authors: Olena Klimchenko, Antonio Di Stefano, Birgit Geoerger, Sofiane Hamidi, Paule Opolon, Thomas Robert, Mélanie Routhier, Jamel El-Benna, Anne-Lise Delezoide, Siham Boukour, Bernadette Lescure, Eric Solary, William Vainchenker, Françoise Norol
Journal: Blood (2010)
Substance P dilates epicardial coronary arteries and increases coronary blood flow in humans.
Authors: D C Crossman, S W Larkin, R W Fuller, G J Davies, A Maseri
Journal: Circulation (1989)

The effects of intracoronary infusions of substance P in conscious humans on epicardial vessel diameter and coronary sinus oxygen saturation were investigated in 13 patients who had angiographically normal coronary arteries. The dose of substance P ranged from 2.8 to 89.6 pmol/min, starting at 2.8 pmol/min and rising by doubling increments. All infusions were performed for 2-minute periods. Epicardial vessel diameter was measured by a computerized analysis system (CAAS) of the angiogram performed at the end of each infusion period. Coronary sinus oxygen saturation (CSO2) was measured continuously by a fiber-optic oximeter catheter in the coronary sinus. A reduction of arterial pressure, indicative of a systemic effect of substance P, occurred only when infusions were 44.8 pmol/min or more. At considerably smaller dosages, a dose-dependent increase in the left anterior descending artery diameter was seen with substance P; maximal dilation occurred at a dosage of 11.2 pmol/min. The percent increase in vessel diameter for this dosage was 29.4 +/- 19.8% (mean +/- SD) at the distal site of analysis and 16.7 +/- 10% at the proximal site of analysis. CSO2 rose in a dose-dependent manner and was maximal at a dosage of 11.2 pmol/min, which caused a 14.6 +/- 7.2% O2 rise above the preinfusion saturation of 43.5 +/- 11.1% O2. As the heart rate-blood pressure double product showed no change, it is argued that these changes in CSO2 probably reflect rises in coronary flow that were seen with dosages of substance P without systemic effect. In three patients, preconstriction induced by ergonovine was reversed by substance P infusions, which produced a degree of dilation equivalent to that of isosorbide dinitrate. We conclude that substance P at very small dosages, which are without peripheral effects, causes in vivo epicardial coronary artery dilatation as well as resistive vessel dilatation in humans.
Effects of resin hydrophilicity on water sorption and changes in modulus of elasticity
Authors: Shuichi Ito, Masanori Hashimoto, Bakul Wadgaonkar, Nadia Svizero, Ricardo M. Carvalho, Cynthia Yiu, Frederick A. Rueggeberg, Stephen Foulger, Takashi Saito, Yoshihiro Nishitani, Masahiro Yoshiyama, Franklin R. Tay, David H. Pashley
Journal: Biomaterials (2005)