tbuckley/cabot-search huggingface dataset:
Minimal impairment of myocardial blood flow responses to exercise in the remodeled left ventricle early after myocardial infarction, despite significant hemodynamic and neurohumoral alterations
Authors: D Haitsma
Journal: Cardiovascular Research (2001)

Objectives: Previous studies have demonstrated a decreased flow reserve in the surviving hypertrophied left ventricle (LV) early after myocardial infarction. We hypothesized that exacerbation of hemodynamic abnormalities and neurohumoral activation during exercise could exhaust coronary flow reserve and thereby impair myocardial O2 supply. Consequently, we studied hemodynamic, neurohumoral and regional myocardial perfusion and metabolic responses to exercise in pigs with LV hypertrophic remodeling 3 weeks after a myocardial infarction produced by permanent left circumflex coronary artery ligation. Methods: Chronically instrumented pigs were exercised on a treadmill up to 85% of maximum heart rate. Pigs with a myocardial infarction (MI) had a lower cardiac output (21%), stroke volume (28%), LV dP/dtmax (18%), systemic (22%) and pulmonary (20%) vascular conductance, and increased left atrial (225%) and pulmonary artery (75%) pressures, compared to normal pigs. In MI, the exercise-induced increases in cardiac pump function, and systemic and pulmonary vasodilation were blunted compared to normals. Consequently, perfusion of visceral organs became impaired during strenuous exercise, but cerebral and skeletal muscle blood flows were maintained. Exercise-induced increases in norepinephrine and endothelin levels were exacerbated and, while relative sympathetic drive was maintained, cardiac responsiveness to norepinephrine was blunted. Despite lower capillary densities in the hypertrophied non-infarcted LV and relative subendocardial hypoperfusion during strenuous exercise, which necessitated a slight increase in O2 extraction, there was no metabolic evidence of overt myocardial ischemia during strenuous exercise as indicated by the arterio–coronary venous pH difference. Conclusions: LV dysfunction and neurohumoral activation were present in pigs with a 3-week-old infarction, particularly during exercise. However, although myocardial perfusion and O2 supply were slightly impaired, myocardial ischemia did not occur even during exercise up to 85% of maximum heart rate, suggesting that perfusion abnormalities do not contribute to LV dysfunction early after infarction.
Implications of pharmacokinetic modeling in risk assessment analysis.
Authors: R J Lutz, R L Dedrick
Journal: Environmental Health Perspectives (1987)

Physiologic pharmacokinetic models are a useful interface between exposure models and risk assessment models by providing a means to estimate tissue concentrations of reactive chemical species at the site of action. The models utilize numerous parameters that can be characterized as anatomical, such as body size or tissue volume; physiological, such as tissue blood perfusion rates, clearances, and metabolism; thermodynamic, such as partition coefficients; and transport, such as membrane permeabilities. The models provide a format to investigate how these parameters can influence the disposition of chemicals throughout the body, which is an important consideration in interpreting toxicity studies. Physiologic models can take into account nonlinear effects related to clearance, metabolism, or transport. They allow for extrapolation of tissue concentration from high dose to low dose experiments and from species to species and can account for temporal variations in dose.
Airway nitric oxide in asthmatic children and patients with cystic fibrosis
Authors: J Dotsch, S Demirakca, HG Terbrack, G Huls, W Rascher, PG Kuhl
Journal: European Respiratory Journal (1996)

We evaluated the effects of asthma and cystic fibrosis on nitric oxide (NO) concentrations in the respiratory tract. NO levels in orally exhaled air and nasal gas samples were studied in 90 asthmatic patients (4-14 yrs), 67 patients with cystic fibrosis (CF) (5-32 yrs), and 68 controls (4-34 yrs). NO concentrations measured by chemiluminescene were correlated with the patient's vital capacity, forced expiratory volume in one second (FEV1) and specific airway resistance. In all groups, NO concentrations in orally-exhaled air correlated with the inhaled ambient NO (r = 0.85-0.91). At an ambient NO concentration of 0 parts per billion (ppb), asthmatic patients exhaled air with higher NO concentrations than cystic fibrosis patients and controls (8.0 +/- 6.1 ppb (n = 33); 4.9 +/- 2.6 ppb (n = 23); and 3.0 +/- 2.5 ppb (n = 37); respectively; p &lt; 0.001). Similar results were obtained for ventilation-adjusted orally-exhaled NO. Nasal NO concentrations were lower in patients with CF (23 +/- 17 ppb) than in controls and asthmatics (96 +/- 47 and 103 +/- 64 ppb; p &lt; 0.001). There was no relationship between nasal or oral NO and pulmonary function tests. Our results suggest that ambient NO levels influence NO concentrations in orally-exhaled air. Like adults, asthmatic children exhale more NO than their controls. Reduced nasal NO concentrations in patients with cystic fibrosis may reflect chronic epithelial cell damage or an increased mucosal barrier impeding NO diffusion into the airway.
PTU-047 Biodegradable Oesophageal Stents In Benign And Malignant Disease – A Single Centre Experience
Authors: SS Siddhi, J Plevris, S Bow
Journal: Gut (2014)

<h3>Introduction</h3> Biodegradable oesophageal stents have been developed recently and the experience in their use and available literature in limited. Their usefulness has been demonstrated in refractory benign strictures in a handful of studies and their role in malignant strictures is relatively untested. We looked at our practice and the clinical outcomes in the use of these stents. <h3>Methods</h3> This is a retrospective observational study looking at electronic case record and endoscopy reports. All patients who had biodegradable stents inserted between March 2011 and September 2013 were included for analysis. Twenty-three stents were inserted in 16 patients. 5 of these patients had 2 stents and one patient had 3 stents over the period of time. Thirteen stents were inserted for benign disease and eight for malignant strictures. There were 9 males and 7 females with age range being between 47 yrs and 101 yrs 2 stents were inserted in 1 patient with postoperative tracheo-oesophageal fistula. <h3>Results</h3> In the benign group, an average of 10.5 endoscopies (0.95/month/patient) and 7.2 dilatations (0.65/month/patient) were necessary prior to stent insertion per patient. Post insertion there was a reduction to 3.5 endoscopies (0.03/month/patient) and 2 dilatations (0.016/month/patient). When the average number of dilatations was analysed pre and post stent insertions per patient per month, there was a significant reduction with a P value of 0.009 on the paired T test. In the benign group, on an average 7 endoscopies and 5 dilatations were avoided/patient. Interval between dilatations increased from 5.2 to 25 weeks. In the malignant group, all patients were successfully bridged to chemo/radiotherapy. 2 out 6 patients went on to metal stents after 3 and 5 months due to disease progression. The stent insertion was technically successful in all cases following a dilatation of the stricture to 12mm at the time of insertion. Four patients complained of some pain post stent insertion (3 in the malignant group and 1 in the benign group). One patient developed sepsis post procedure but recovered well with a course of antibiotics. No other complications were noted. In all cases where a check up endoscopy was done, the stent had disintegrated within 8–12 weeks. <h3>Conclusion</h3> BD stents are of value in recurrent benign oesophageal strictures as they reduced the number and frequency of dilatations. The BD stents successfully bridge patients with malignant strictures to oncological therapies. Insertion of a BD stent does not preclude a later insertion of a permanent metal stent. Stent insertion was technically successful and safe. <h3>Disclosure of Interest</h3> None Declared.
Adherence of Type 1-Fimbriated <i>Escherichia coli</i> to Uroepithelial Cells
Authors: Suzanne E. Geerlings, Ruby Meiland, Emiel C. van Lith, Ellen C. Brouwer, Wim Gaastra, Andy I.M. Hoepelman
Journal: Diabetes Care (2002)

OBJECTIVE—Women with diabetes have bacteriuria more often than women without diabetes. Because Escherichia coli adhere better to vaginal cells of nondiabetic patients with recurrent urinary tract infections (UTIs) than to those obtained from healthy control subjects, it was hypothesized that E. coli adhere more to the uroepithelial cells of diabetic women, either because of substances excreted in the urine (e.g., albumin, glucose, and Tamm Horsfall protein) or because of a difference in the uroepithelial cells. RESEARCH DESIGN AND METHODS—A T24 bladder cell line and uroepithelial cells of 25 diabetic women and 19 control subjects were incubated with three different E. coli strains. RESULTS—The mean numbers of type 1-fimbriated E. coli that adhered to diabetic and control cells were 12.9 and 6.1 (P = 0.001), respectively, whereas those of P-fimbriated E. coli were 8.8 and 8.1 (P = 0.8), and those of nonfimbriated E. coli were 2.7 and 3.4 (P = 0.4). The addition of various substances did not influence the adherence of E. coli to a T24 bladder cell line. CONCLUSIONS—Type 1-fimbriated E. coli adhere more to diabetic than to control uroepithelial cells.
Bone and joint symptoms in Paget's disease.
Authors: J Winfield, T C Stamp
Journal: Annals of the Rheumatic Diseases (1984)

Fifty patients with Paget9s disease of bone were reviewed with regard to the basis of their symptoms and the long-term results of treatment. Twenty-four patients (48%) presented with pain localised within bone, while 17 (34%) presented with symptoms of degenerative joint disease. Three patients presented with bone pain and arthritis and the remaining six with fractures, ataxia, or painless deformity. Symptomatic osteoarthritis of the hip (OA) developed in 25 patients (50%) with approximately half developing radiological changes identical to those of idiopathic OA. Among the other patients those with coxa vara tended to show medial (rather than superior) joint space narrowing and severe Paget9s disease on both sides of the joint. Arthritic pain, stiffness, and reduced mobility in other joints (knee, ankle, and wrist) were associated clinically with bone deformity adjacent to the affected joint and radiologically with distorted articular surfaces and narrowed joint spaces; sclerosis, subarticular cyst formation, and osteophytosis were usually absent. Fifteen patients were treated with calcitonin for bone pain alone; all claimed long-term 9good to complete9 relief. By contrast, none of the 14 with arthritic symptoms responded to calcitonin when assessed retrospectively. Results of surgical and other medical treatment were analysed. Careful clinical evaluation is a prerequisite for optimal treatment in Paget9s disease.
Efficacy and safety of atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus (SLE): 52-week data (APRIL-SLE randomised trial)
Authors: David Isenberg, Caroline Gordon, Daiana Licu, Samuel Copt, Claudia Pena Rossi, David Wofsy
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Despite advances in systemic lupus erythematosus (SLE) treatment, many patients suffer from the disease and side effects. Atacicept is a fusion protein that blocks B-lymphocyte stimulator and a proliferation-inducing ligand, which are increased in patients with SLE. <h3>Methods</h3> In this double-blind, placebo-controlled study, patients with moderate-to-severe SLE were randomised to atacicept 75 mg or atacicept 150 mg administered subcutaneously, or placebo twice-weekly for 4 weeks, then weekly for 48 weeks. Primary and secondary efficacy measures were the proportion of patients experiencing at least one flare of British Isles Lupus Assessment Group A or B, and time to first flare, respectively. <h3>Results</h3> Enrolment in the atacicept 150 mg arm was discontinued prematurely due to two deaths. In the intention-to-treat population (n=461), there was no difference in flare rates or time to first flare between atacicept 75 mg and placebo. Analysis of patients treated with atacicept 150 mg suggested beneficial effect versus placebo in flare rates (OR: 0.48, p=0.002) and time to first flare (HR: 0.56, p=0.009). Both atacicept doses were associated with reductions in total Ig levels and anti-dsDNA antibodies, and increases in C3 and C4 levels. Most treatment-emergent adverse events were mild or moderate. <h3>Conclusions</h3> There was no difference between atacicept 75 mg and placebo for flare rate or time to first flare. Analysis of atacicept 150 mg suggested benefit. <h3>Trial registration number</h3> EudraCT: 2007-003698-13; NCT00624338.
Stage I NSCLC: elucidating the prognostic factors
Authors: D. Pham, D. H Harpole
Journal: Thorax (2009)

Non-small cell lung cancer (NSCLC) remains the number one cause of cancer related deaths.1 While early stage NSCLC portends the best survival following complete surgical resection, as many as 37% of patients with stage I disease have recurrence within 5 years of diagnosis.2 Several studies have investigated the role of adjuvant chemotherapy for early stage disease.3–6 However, the benefit of adjuvant therapy was mainly in patients with stage II and IIIA disease. Significant progress in improving the survival of patients with stage I NSCLC is lacking.

In this issue, Hung and colleagues7 address two very important issues with regard to the management of early stage NSCLC (see page 192) : (1) the prognostic predictors of survival in patients with recurrence and (2) the optimal treatment for recurrent disease. In this retrospective study of 970 …
Healing Processes in Wounds
Authors: L. A. Rauscher
Journal: BMJ (1967)

drugs they prescribe would tend to vitiate the " rapport existing between the doctor and patient " ?Expecting trust or rapport to be possible in the face of such callous indifference to the safety of patients and others seems utterly incomprehensible.Equally dangerous is the habit of some doctors of not offering information on whether small or large amounts of alcohol can alter the effectiveness of any drug and its safety.-I am, etc., London S.W. 1.
Parathyroid hormone and lipopolysaccharide induce murine osteoblast-like cells to secrete a cytokine indistinguishable from granulocyte-macrophage colony-stimulating factor.
Authors: M C Horowitz, D L Coleman, P M Flood, T S Kupper, R L Jilka
Journal: Journal of Clinical Investigation (1989)

Osteoblasts are the cells responsible for the secretion of collagen and ultimately the formation of new bone. These cells have also been shown to regulate osteoclast activity by the secretion of cytokines, which remain to be defined. In an attempt to identify these unknown cytokines, we have induced primary murine osteoblasts with two bone active agents, parathyroid hormone (PTH) and lipopolysaccharide (LPS) and analyzed the conditioned media (CM) for the presence of specific cytokines. Analysis of the CM was accomplished by functional, biochemical, and serological techniques. The data indicate that both PTH and LPS are capable of inducing the osteoblasts to secrete a cytokine, which by all of the techniques used, is indistinguishable from granulocyte-macrophage colony-stimulating factor (GM-CSF). Secretion of GM-CSF is not constitutive and requires active induction. Production of the cytokine is dependent on the dose of PTH or LPS added. It has been demonstrated that the addition of GM-CSF to bone marrow cultures results in the formation of increased numbers of osteoclasts. Therefore, these data suggest that osteoblasts not only participate in bone remodeling by formation of new matrix but may regulate osteoclast activity indirectly by their ability to regulate hematopoiesis.
TIGIT safeguards liver regeneration through regulating natural killer cell-hepatocyte crosstalk
Authors: Jiacheng Bi, Xiaodong Zheng, Yongyan Chen, Haiming Wei, Rui Sun, Zhigang Tian
Journal: Hepatology (2014)

Overactivation of innate immunity, particularly natural killer (NK) cells, is harmful to liver regeneration; however, the molecular mechanisms that limit NK cell overactivation during liver regeneration are still elusive. Here we show that a coinhibitory receptor, T cell Ig and ITIM domain (TIGIT), was selectively up-regulated on NK cells, along with high expression of its ligand, poliovirus receptor (PVR/CD155), on hepatocytes during liver regeneration. The absence of TIGIT impaired liver regeneration in vivo , along with overactivation of NK cells and higher NK-derived interferon-gamma (IFN-γ) production. We also show that both depletion of NK cells and deficiency of IFN-γ, but not deficiency of RAG1, rescued impaired liver regeneration caused by the absence of TIGIT. Adoptive transfer of Tigit –/– NK cells into NK-deficient Nfil3 –/– mice sufficiently led to impairment of liver regeneration. On the other hand, silencing PVR in hepatocytes rescued impaired liver regeneration caused by TIGIT deficiency in vivo , while blockade of TIGIT in NK-hepatocyte coculture increased IFN-γ production by NK cells in vitro . Conclusion : TIGIT is a safeguard molecule to improve liver regeneration through negatively regulating NK-hepatocyte crosstalk. This finding suggests a novel mechanism of NK cell self-tolerance towards regenerative hyperplasia of the host. (Hepatology 2014;60:1389–1398)
Familial pancreatic cancer
Authors: R H Hruban, G M Petersen, M Goggins, A C Tersmette, G J Offerhaus, F Falatko, C J Yeo, S E Kern
Journal: Annals of Oncology (1999)

For many years anecdotal case reports have suggested that pancreatic cancer aggregates in some families.Two recent advances have established that this is in fact the case. First, large registries, such as the National Familial Pancreas Tumor Registry (NFPTR) at Johns Hopkins, have identified a number of families in which multiple family members have been diagnosed with pancreatic cancer. As a result, the patterns of inheritance of pancreatic cancer can now be studied on a scale not possible before. Second, advances in molecular genetic techniques make it possible to test members of these families for germline mutations in known candidate cancer causing genes. As a result, some of the genetic alterations responsible for the familial aggregation of pancreatic cancer have been identified in some families.The NFPTR has enrolled 362 families in which at least one family member has been diagnosed with pancreatic cancer. These include 151 families in which at least two first-degree relatives have been diagnosed with pancreatic cancer. Analysis of these families has revealed that even second-degree relatives of patients from these families are at increased risk of developing pancreatic cancer. In addition, a number of kindreds which exhibit aggregation of cancer have been tested for germline mutations in known cancer causing genes. Germline mutations in BRCA2 have been shown to predispose to both breast and pancreatic cancer, germline mutations in p16 to melanoma and pancreatic cancer (the FAMMM syndrome), and genetic mutations in STK11/LKB1 to pancreatic cancer in patients with the Peutz-Jeghers Syndrome (PJS).Pancreatic cancer aggregates in some families, and relatives of patients with pancreatic cancer have an increased risk of developing pancreatic cancer themselves. The genetic basis for the familial aggregation of pancreatic cancer has been shown to be germline mutations in known cancer causing genes in some of these families.
Inertial Focusing in Microfluidics
Authors: Joseph M. Martel, Mehmet Toner
Journal: Annual Review of Biomedical Engineering (2014)

When Segré and Silberberg in 1961 witnessed particles in a laminar pipe flow congregating at an annulus in the pipe, scientists were perplexed and spent decades learning why such behavior occurred, finally understanding that it was caused by previously unknown forces on particles in an inertial flow. The advent of microfluidics opened a new realm of possibilities for inertial focusing in the processing of biological fluids and cellular suspensions and created a field that is now rapidly expanding. Over the past five years, inertial focusing has enabled high-throughput, simple, and precise manipulation of bodily fluids for a myriad of applications in point-of-care and clinical diagnostics. This review describes the theoretical developments that have made the field of inertial focusing what it is today and presents the key applications that will make inertial focusing a mainstream technology in the future.
Infective Endocarditis in Hypertrophic Cardiomyopathy
Authors: Paolo Spirito, Claudio Rapezzi, Pietro Bellone, Sandro Betocchi, Camillo Autore, Maria Rosa Conte, Gian Paolo Bezante, Paolo Bruzzi
Journal: Circulation (1999)

Background —The literature on infective endocarditis in hypertrophic cardiomyopathy (HCM) is virtually confined to case reports. Consequently, the risk of endocarditis in HCM remains undefined. Methods and Results —We assessed the occurrence of endocarditis in 810 HCM patients evaluated between 1970 and 1997. Endocarditis was diagnosed in 10 patients, 2 of whom were excluded from analysis of prevalence and incidence because they were referred for acute endocarditis. At first evaluation, echocardiographic features consistent with prior endocarditis were identified in 3 of 808 patients, a prevalence of 3.7 per 1000 patients (95% CI, 0.8 to 11). Of 681 patients who were followed, 5 developed endocarditis, an incidence of 1.4 per 1000 person-years (95% CI, 0.5 to 3.2); outflow obstruction was present in each of these 5 patients and was associated with the risk of endocarditis ( P =0.006). In the 224 obstructive patients, incidence of endocarditis was 3.8 per 1000 person-years (95% CI, 1.6 to 8.9) and probability of endocarditis 4.3% at 10 years. Left atrial size was also associated with the risk of endocarditis ( P =0.007). In patients with both obstruction and atrial dilatation (≥50 mm), incidence of endocarditis increased to 9.2 per 1000 person-years (95% CI, 2.5 to 23.5). Analysis of all 10 patients with endocarditis identified outflow obstruction in each and atrial dilatation in 7. Conclusions —Endocarditis in HCM is virtually confined to patients with outflow obstruction and is more common in those with both obstruction and atrial dilatation. These results indicate that antibiotic prophylaxis is required only in patients with obstructive HCM.