tbuckley/cabot-search huggingface dataset:
Intrinsic Histological Abnormalities of Aortic Root and Ascending Aorta in Tetralogy of Fallot
Authors: J.L. Tan, P.A. Davlouros, K.P. McCarthy, M.A. Gatzoulis, S.Y. Ho
Journal: Circulation (2005)

Dilatation of the aortic root is a known feature in tetralogy of Fallot (TOF) patients with pulmonary stenosis (PS) or pulmonary atresia (PA). We hypothesized that intrinsic histological abnormalities of the aortic wall present since infancy are an important causative factor leading to aortic root dilatation.We examined the aortic histology of 17 cases with TOF and PS/PA from our cardiac morphology archive and compared them with a control group of normal aortas. Measured circumference of the aortic root at the sinotubular junction and at the ascending aorta was indexed to the left ventricle. Aortic walls were studied by light microscopy with the use of various stains. Seventeen TOF cases (7 with PS, 10 with PA) including 7 infants, 2 children, and 8 adults were compared with 11 hearts with normal aorta. Aortic root circumference to left ventricular index and ascending aortic circumference to left ventricular index were 1.24+/-0.25 and 1.37+/-0.24, respectively, in the TOF group versus 0.89+/-0.10 and 0.88+/-0.11, respectively, in the control group (P<0.001). Histological changes of grade 2 or 3 were present in 29% (medionecrosis), 82% (fibrosis), 35% (cystic medial necrosis), and 59% (elastic fragmentation) in the ascending aorta of the TOF group. Histology grading scores were significantly higher in the TOF group (median score, 7; range, 1 to 12) compared with normal controls (median score, 2; range, 0 to 6) and correlated with the ascending aortic circumference to left ventricular index (r=0.525, P=0.03).There are marked histological abnormalities in the aortic root and ascending aortic wall of patients with TOF present from infancy, suggesting a causative mechanism for subsequent aortic root dilatation.
Trimeric G protein-CARMA1 axis links smoothened, the hedgehog receptor transducer, to NF-κB activation in diffuse large B-cell lymphoma
Authors: Changju Qu, Yadong Liu, Kranthi Kunkalla, Rajesh R. Singh, Marzenna Blonska, Xin Lin, Nitin Kumar Agarwal, Francisco Vega
Journal: Blood (2013)
Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5′ olfactory receptor gene cluster
Authors: Nadia Solovieff, Jacqueline N. Milton, Stephen W. Hartley, Richard Sherva, Paola Sebastiani, Daniel A. Dworkis, Elizabeth S. Klings, Lindsay A. Farrer, Melanie E. Garrett, Allison Ashley-Koch, Marilyn J. Telen, Supan Fucharoen, Shau Yin Ha, Chi-Kong Li, David H. K. Chui, Clinton T. Baldwin, Martin H. Steinberg
Journal: Blood (2009)
Inhibitory effects of <i>Rumex japonicus</i> Houtt. on the development of atopic dermatitis-like skin lesions in NC/Nga mice
Authors: H-S. Lee, S-K. Kim, J-B. Han, H-M. Choi, J-H. Park, E-C. Kim, M-S. Choi, H-J. An, J-Y. Um, H-M. Kim, B-I. Min
Journal: British Journal of Dermatology (2006)

Rumex japonicus Houtt. (RJH) is one of the herbs used in Eastern countries for the treatment of atopic dermatitis (AD). It has been shown to have an antioxidative effect in human skin disease.To examine whether RJH extract (RJH-E) suppresses the development of AD-like skin lesions in NC/Nga mice, which are induced by the repeated application of picryl chloride (PC).The efficacy of RJH-E in NC/Nga mice was assessed by measuring symptom severity, scratching behaviour, Staphylococcus aureus numbers on an ear, and serum levels of IgE, interleukin (IL)-4 and interferon (IFN)-gamma.Oral administration of RJH-E to NC/Nga mice treated with PC inhibited the development of AD-like skin lesions as exemplified by a significant decrease in total skin symptom severity scores, and a decrease in hypertrophy, hyperkeratosis and infiltration of inflammatory cells in the skin. The scratching behaviour and numbers of S. aureus, which are known to be exacerbated in AD, were also significantly reduced by RJH-E. No significant change was observed in the serum levels of IFN-gamma, whereas IgE and IL-4 levels were significantly reduced by RJH-E.These results suggest that RJH-E inhibits the development of AD-like skin lesions in NC/Nga mice by suppressing the T-helper 2 cell response. Our results indicate that RJH treatment could provide an effective alternative therapy for the management of AD.
American Values and Health Care Reform
Authors: Thomas H. Murray
Journal: New England Journal of Medicine (2009)

With the national debate over health care reform careening between tired, well-rehearsed talking points, on the one hand, and deep-in-the-weeds debates over technical details, initiatives, and financing mechanisms, on the other, many people find themselves feeling frustrated and left out of the conversation. Yet most thoughtful Americans would have something meaningful to say about the values we should choose for the foundation of our system of health care.1 And by focusing on these fundamental considerations, perhaps we can deepen and broaden the discussion of values and public policy.Our discussion about health care reform is enriched, for instance, when we . . .
Fortnightly Review: Insulin resistance
Authors: A. J Krentz
Journal: BMJ (1996)

<h3>Summary points</h3> Insulin resistance is a state in which normal concentrations of insulin produce a subnormal biological response Patients with insulin resistance have hyperinsulinaemia together with normoglycaemia or hyperglycaemia Insulin resistance is commonly associated with obesity, non-insulin dependent diabetes mellitus, and essential hypertension The insulin resistance syndrome includes impaired insulin stimulated glucose uptake, hyperinsulinaemia, glucose intolerance, hypertension, and dyslipidaemia Drugs such as corticosteroids, ß blockers, and high dose thiazides can exacerbate insulin resistance; angiotensin converting enzyme inhibitors and (alpha) blockers may reduce resistance Reducing insulin resistance is important in managing non-insulin dependent diabetes—for example, by losing weight, aerobic exercise, and stopping smoking; moderate alcohol consumption improves insulin resistance Metformin improves multiple aspects of the insulin resistance syndrome. Novel insulin action enhancing drugs including the thiazolidinediones are under evaluation
New Insights Into the Gating Mechanisms of Cardiac Ryanodine Receptors Revealed by Rapid Changes in Ligand Concentration
Authors: Rebecca Sitsapesan, Richard A.P. Montgomery, Alan J. Williams
Journal: Circulation Research (1995)

Abstract We have developed a novel technique for incorporation of sheep cardiac sarcoplasmic reticulum (SR) Ca 2+ -release channels into planar phospholipid bilayers in order to investigate changes in [Ca 2+ ] on a physiological time scale and have investigated whether the rate of change of cytosolic [Ca 2+ ] has a direct effect on the gating of the cardiac SR Ca 2+ -release channel. Vesicles of heavy SR were incorporated into planar phospholipid bilayers painted on glass pipettes, and an established technique for rapid solution exchanges at excised membrane patches was modified to allow solution changes to be made at the bilayer within 10 ms. For a given change in [Ca 2+ ], we demonstrate that the open probability (Po) is similar whether the cytosolic [Ca 2+ ] is increased rapidly (10 ms) or slowly (1 s) and appears to be no different from the Po measured under steady state conditions that were recorded by using conventional bilayer techniques. We also demonstrate that no desensitization or inactivation occurs at −40 mV when the channel is activated by Ca 2+ alone or in the presence of other channel activators, ATP or EMD 41000. However, at +40 mV, rapid channel activation followed by inactivation was observed. The probability of such voltage-dependent inactivation appears to depend on the mechanism of channel activation.
Abnormal exercise hemodynamics in cardiac allograft recipients 1 year after cardiac transplantation. Relation to preload reserve.
Authors: J D Hosenpud, M J Morton, R A Wilson, G A Pantely, D J Norman, M A Cobanoglu, A Starr
Journal: Circulation (1989)

The well-established elevation in left ventricular filling pressures during exercise in patients after transplantation may contribute to decreased exercise tolerance. A proposed mechanism for this increase in filling pressures is an abnormal pressure-volume homeostasis of the transplanted heart. Twenty-three patients undergoing routine 1-year evaluations performed supine bicycle exercise during right heart catheterization. Within 24 hours, these patients underwent supine bicycle exercise to the identical work load during radionuclide ventriculography. For the group, resting hemodynamics and resting left and right ventricular ejection fractions were normal. With exercise, right atrial and pulmonary wedge pressure rose markedly (from 6 +/- 2 to 14 +/- 7 mm Hg, p less than 0.0001, and from 10 +/- 3 to 20 +/- 6 mm Hg, p less than 0.0001, respectively). Left ventricular ejection fraction increased appropriately with exercise (from 0.58 +/- 0.08 to 0.63 +/- 0.07, p = 0.004). End-diastolic volume also increased mildly (from 100 +/- 31 to 117 +/- 39 ml, p = 0.001), but change in end-diastolic volume was highly variable. Patients with little or no change in end-diastolic volume with exercise had the greatest resting and exercise left ventricular filling pressures resulting in significant negative correlations between filling pressures and change in end-diastolic volume (r = -0.64, p = 0.002 and r = -0.50, p = 0.025, respectively). Negative linear relations between exercise left ventricular filling pressures or resting heart rates and donor to recipient body weight ratio (r = -0.35, p = 0.10, and r = -0.37, p = 0.06, respectively) suggested that initial donor heart size influenced subsequent cardiac function.(ABSTRACT TRUNCATED AT 250 WORDS)
Delayed haemorrhagic disease of the newborn.
Authors: I F Roberts, P J McHugh
Journal: BMJ (1979)

0 1 2 3 4 5 6 7 8 9 Days since transplantation Serum creatinine concentration by time.figure are transformed back into the original units serum creatinine concentrations change smoothly with time.A quadratic curve fits the data reasonably well, although a more appropriate model might be to fit separate exponential curves to the periods of improvement and deterioration.It is hard to see why they have chosen to use the artificial method of taking reciprocals rather than study the raw data.The authors rightly say that "a time when renal allograft rejection occurs can be determined only if there is a sudden event rather than slow changes from a non-rejecting to a rejecting state."I cannot accept that they have established this.Lastly, their approach assumes that onset of rejection results in an immediate rise in serum creatinine.Is this really so ?
Aerosolized Pancreatic Dornase and Antibiotics in Pulmonary Infections
Authors: Robert Spier
Journal: JAMA (1961)

This study was undertaken to determine whether an enzyme, pancreatic dornase, plus an antibiotic aerosolized for endobronchial application via the intermittent positive pressure breathing/ inspiration machine would be a valuable adjunctive measure to systemic antibiotics in the treatment of pneumonias. Thirty patients with pneumonia have been successfully treated by this method. Half of these patients had staphylococcal pneumonia (some with lung abscesses). Pancreatic dornase was effective in lysing the endobronchial exudate, which became thinner and more easily expelled. Removal of a thickened exudate by this enzyme makes concurrent and subsequent application of an aerosolized antibiotic more effective.
Lead in Paint: Three Decades Later and Still a Hazard for African Children?
Authors: Angela Mathee, Halina Röllin, Jonathan Levin, Inakshi Naik
Journal: Environmental Health Perspectives (2006)

Surveys undertaken in South Africa have shown that a large proportion of children are exposed to lead from a variety of sources.The overall objective of this work was to examine, through a series of small-scale investigations, the role of lead-based paint in the blood lead distribution of South African children.We suggest that the African public health community strengthen their efforts to prevent lead poisoning in African children through a holistic approach that includes the promulgation and enforcement of appropriate legislation as well as research to identify further sources of exposure to lead.
EFFECT OF VALSARTAN ON SUPPRESSION OF NEOINTIMAL HYPERPLASIA AFTER DRUG-ELUTING STENTS AND ON REGRESSION OF NATIVE PLAQUE VOLUME: THE VAL-SUPPRES RANDOMIZED CONTROLLED TRIAL
Authors: Duk-Woo Park, Yangsoo Jang, Ki-Bae Seung, Hyeon-Cheol Gwon, Seung-Jea Tahk, Chang Hoon Lee, Gyung-Min Park, Yong-Giun Kim, Ki Won Hwang, Jung-Min Ahn, Hae Geun Song, Won-Jang Kim, Jong-Young Lee, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2011)
P82 What is the role of chest computed tomography in children with parapneumonic effusion?
Authors: A. Parmar, G. Peek, R. Firmin, H. Pandya, E. Gaillard
Journal: Thorax (2010)

<h3>Introduction</h3> The incidence of parapneumonic effusion in children has been rising in the UK since the mid 1990s (1). There is anecdotal evidence that the number of complicated cases with more severe illness may be increasing. This is frequently due to severe underlying, often necrotic pneumonia, caused by unusual organisms (2), pulmonary abscesses or bronchopleural fistulas. Chest ultrasound does not reliably identify these processes and CT scanning is the investigation of choice. However, there has been little research in the use of chest CT in children with parapneumonic effusion and its use remains controversial. <h3>Aims</h3> To evaluate the usefulness of chest CT in children with parapneumonic effusion. <h3>Methods</h3> We retrospectively reviewed the medical notes and imaging of all children admitted between January 2004 and December 2009 with a diagnosis of parapneumonic effusion to the University Hospitals of Leicester NHS Trust. <h3>Results</h3> A total of 183 children were identified. Of this number, 51 children underwent CT scanning. The main indications for chest CT were as follows: slow/no response to IV antibiotic treatment (25%), failed attempt at chest drainage without urokinase (24%) and acute critical clinical deterioration (16%). Other indications included failure of chest drainage with urokinase, failure of surgical intervention or investigation for other pathology. A range of pathological findings were identified with CT. 38% of the CT scans identified collapse consolidation. Other pathology was also identified that was not apparent on ultrasound scan. 4% identified pulmonary abscess, 4% identified areas of lung necrosis, 4% identified broncho-pleural fistula and 6% identified cavitating pneumonias. <h3>Conclusion</h3> (1) A chest CT is useful in children with a complicated parapneumonic effusion to detect lung pathology not readily detected with chest ultrasound. (2) A small number of children have a pulmonary abscess complicating the parapneumonic effusion. (3) Further research is needed to establish the role and timing of chest CT scanning in children with infective pleural disease.
Surgical lung biopsy in patients with hematological malignancy or hematopoietic stem cell transplantation and unexplained pulmonary infiltrates: Improved Outcome with specific diagnosis
Authors: Mamoon Zihlif, Geeta Khanchandani, Huma P. Ahmed, Ayman O. Soubani
Journal: American Journal of Hematology (2005)

Using a retrospective review of medical records, we sought the findings of surgical lung biopsy (SLB) in patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT) and unexplained pulmonary infiltrates and to determine the impact of this procedure on management and outcome of these patients. Sixty-two patients who underwent SLB were evaluated; 31 patients had underlying hematological malignancy and 31 patients were HSCT recipients; 58% of whom underwent allogeneic HSCT. Thirty-three patients (53%) had focal infiltrates on chest CT scan while 29 (47%) had diffuse infiltrates. Thirteen patients were mechanically ventilated prior to SLB, and 27 (43%) were neutropenic. There were 66 diagnoses in the 62 patients, 44 (67%) were specific and 22 (33%) were nonspecific. The most common specific diagnoses were infection (29%), malignancy (27%), and inflammatory conditions (11%). Aspergillosis was the most common diagnosis of all biopsies (21%). SLB led to a change in therapy in 40% of patients and was associated with complications in 7 patients (11%). Specific diagnosis was more likely to lead to a change in therapy (48% vs. 27%, P = 0.06) and was associated with a lower mortality when compared to a nonspecific finding (30% vs. 59%, P = 0.02). Nonspecific diagnosis, on the other hand, was seen more in patients on mechanical ventilation prior to SLB compared to those off mechanical ventilation (69% vs. 27%, P = 0.02). SLB provides a specific diagnosis in the majority of patients with hematologic malignancy or HSCT recipients and unexplained pulmonary infiltrates. Specific diagnosis is more likely to lead to a change in therapy and is associated with a better outcome.
Managing anovulatory infertility and polycystic ovary syndrome
Authors: Adam H Balen, Anthony J Rutherford
Journal: BMJ (2007)

In this second overview of the current management of infertility we discuss anovulatory infertility and polycystic ovary syndrome.This syndrome (formerly known as Stein-Leventhal syndrome) is the most common hormonal disturbance in women-around one fifth of women in the United Kingdom are affected.It is also the most common reason for women not to ovulate, and the combination of being overweight and having polycystic ovary syndrome can have a profound effect on reproductive health.
Prolonged treatment of pulmonary sarcoidosis with corticosteroids
Authors: C. Hoyle, H. Smyllie, D. Leak
Journal: Thorax (1967)

The results are described of prolonged corticosteroid treatment in 52 patients with pulmonary sarcoidosis observed for a mean duration of 10·5 years from diagnosis. Twenty of the patients were treated for less than one year, the remainder for a mean of five years. The mean length of observation after discontinuing treatment was 5·5 years. Selection of patients for treatment was based on (1) evidence from radiographic observation, even for two years or more, that the disease was progressive so that spontaneous remission was improbable; and (2) evidence of disturbed lung function, especially the onset of dyspnoea or an impaired diffusing capacity. Treatment, conveniently with prednisone at a maintenance dose of about 15 mg. daily, should be continued for at least a year and often for much longer until withdrawal is not followed by radiographic relapse. Such treatment does not increase the chance of a complete remission even when given at an early stage of the disease; and relief of dyspnoea is unpredictable and seldom considerable. But prolonged treatment will halt progressive lung destruction and appears to curb the eventual mortality.
Transduction of Human Primitive Repopulating Hematopoietic Cells With Lentiviral Vectors Pseudotyped With Various Envelope Proteins
Authors: Yoon-Sang Kim, Matthew M Wielgosz, Phillip Hargrove, Steven Kepes, John Gray, Derek A Persons, Arthur W Nienhuis
Journal: Molecular Therapy (2010)

Lentiviral vectors are useful for transducing primitive hematopoietic cells. We examined four envelope proteins for their ability to mediate lentiviral transduction of mobilized human CD34(+) peripheral blood cells. Lentiviral particles encoding green fluorescent protein (GFP) were pseudotyped with the vesicular stomatitis virus envelope glycoprotein (VSV-G), the amphotropic (AMPHO) murine leukemia virus envelope protein, the endogenous feline leukemia viral envelope protein or the feline leukemia virus type C envelope protein. Because the relative amount of genome RNA per ml was similar for each pseudotype, we transduced CD34(+) cells with a fixed volume of each vector preparation. Following an overnight transduction, CD34(+) cells were transplanted into immunodeficient mice which were sacrificed 12 weeks later. The average percentages of engrafted human CD45(+) cells in total bone marrow were comparable to that of the control, mock-transduced group (37-45%). Lenti-particles pseudotyped with the VSV-G envelope protein transduced engrafting cells two- to tenfold better than particles pseudotyped with any of the gamma-retroviral envelope proteins. There was no correlation between receptor mRNA levels for the gamma-retroviral vectors and transduction efficiency of primitive hematopoietic cells. These results support the use of the VSV-G envelope protein for the development of lentiviral producer cell lines for manufacture of clinical-grade vector.
Controversies in the Treatment of Early-Stage Hodgkin’s Lymphoma
Authors: Dan L. Longo, James O. Armitage
Journal: New England Journal of Medicine (2015)

Hodgkin's lymphoma affects about 8000 patients a year in the United States, and with available therapies, about 7000 of them will be cured. Although room for improvement still exists, recent clinical research has focused on determining how little therapy can be given to maintain the current high cure rates. The focus on cutting back therapy to the bare minimum is related to well-defined, treatment-related late toxic effects. The life-threatening or fatal toxic effects of radiation therapy include second cancers (including cancers of the breast, skin, thyroid, lung, and stomach) and premature coronary-artery disease. Life-threatening or fatal toxic effects of chemotherapy . . .
Rectal carcinoid tumor, 6 mm in diameter, with lymph node metastases
Authors: T. Shinohara, K. Hotta, T. Oyama
Journal: Endoscopy (2008)

A 60-year-old man was referred to our hospital because of a positive fecal occult blood test. Colonoscopy revealed a hemispheric submucosal tumor, 8 mm in diameter, at the lower rectum ([Fig. 1] a). There was neither a central depression nor ulceration on the lesion. The pathological diagnosis of the biopsy specimen was carcinoid tumor. Abdominal CT detected no liver or lymph node metastasis. The lesion was diagnosed as a rectal carcinoid tumor confined to the submucosal layer, and therefore endoscopic submucosal resection with a ligating device (ESMR-L) [1] was performed.
Psychosomatic Symptoms in Adolescent Twins
Authors: Irma Moilanen
Journal: Psychotherapy and Psychosomatics (1991)

In a cohort study of 234 twin pairs followed from pregnancy to 12–20 years of age the psychosomatic symptoms of adolescents were inquired from their parents. Girls had symptoms more often than boys. Intrapair concordances were high. The mothers' favorite children had psychosomatic complaints more often than the father's favorites or those who were equally close to each parent. Psychosomatic complaints were more frequent in the submissive members of twin pairs and nervous symptoms in the dominant ones.
Management of the Fat Child
Authors: J. A. McCluskie
Journal: BMJ (1967)

<h3>ABSTRACT</h3> CRISPR-based screening methods using single-cell RNA sequencing (scRNA-seq) technology enable comprehensive profiling of gene perturbations from knock-out mutations. However, evaluating substitution mutations using scRNA-seq is currently limited. We combined CRISPR RNA-guided deaminase and scRNA-seq technology to develop a platform for introducing mutations in multiple genes and assessing the mutation-associated signatures. Using this platform, we generated a library consisting of 420 sgRNAs, performed sgRNA tracking analysis, and assessed the effect size of the response to vemurafenib in the melanoma cell line, which has been well-studied via knockout-based drop-out screens. However, a substitution mutation library screen has not been applied and transcriptional information for mechanisms of action was not assessed. Our platform permits discrimination of several candidate mutations that function differently from other mutations by integrating sgRNA candidates and gene expression readout. We anticipate that our platform will enable high-throughput analyses of the mechanisms related to a variety of biological events.