tbuckley/cabot-search huggingface dataset:
Prolonged Survival of Lymphocytes With Chromosomal Defects in Children Treated With 1,3-Bis(2-Chloroethyl)-1-Nitrosourea&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Emma K. Harrod, Jean A. Cortner
Journal: JNCI Journal of the National Cancer Institute (1968)

Chromosomal defects were observed in as many as 65% of the cultured circulating leukocytes of 6 children with acute leukemia and 2 with Ewing's sarcoma of the femur who were treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a lipid-soluble alkylating agent. These defects, which included breaks in chromatids and chromosomes and interchanges of chromatin between 2 or more chromosomes to form triradials, quadriradials, and other multibranched chromosomes, persisted for 1–11½ months after BCNU therapy. The other chemotherapeutic agents and previous diseases of these patients are unlikely to have produced these defects, since a similar group of control patients had no significant number of chromosomal defects in their cultured leukocytes. Identical defects were produced by in vitro BCNU treatment of cultured leukocytes from 2 normal adults. In vitro studies also showed that BCNU affects all chromosomes randomly; however, the effects do not appear immediately after treatment. These chromosomal defects were found only in cells presumed to be lymphocytes in spite of BCNU's lethal effect on many cell types. This specificity may be more apparent than real and secondary to known characteristics of lymphocytes and their response to phytohemagglutinin. Despite the large number of agents capable of damaging chromosomes, only irradiation and, recently, lysergic acid diethylamide have been reported to produce defects which persist for long periods following in vivo therapy.
Angiotensin II and calcium blockers prevent glomerular phenotypic changes in remnant kidney model.
Authors: A Hamaguchi, S Kim, H Wanibuchi, H Iwao
Journal: Journal of the American Society of Nephrology (1996)

Recent studies on various models of glomerular diseases indicate that glomerular injury is associated with the phenotypic modulation of glomerular cells. However, the effect of renoprotective agents on glomerular phenotype remains to be determined. This study examined the effects of angiotensin II Type 1 (AT1) receptor antagonists and calcium antagonists on glomerular phenotypic changes in rats with subtotal renal ablation. Rats were subjected to 5/6 nephrectomy and were given oral TCV-116, a selective AT1 receptor antagonist (1 mg/kg), manidipine, a dihydropyridine calcium antagonist (3 mg/kg), or vehicle for 8 wk. Glomerular phenotypic modulation was determined by the staining of alpha-smooth muscle actin and desmin in glomerular cells with an immunohistochemical technique. At the start of drug treatment, alpha-smooth muscle actin and desmin were already significantly expressed in the glomerular cells of 5/6-nephrectomized rats, in contrast to a negligible glomerular expression of these proteins in sham-operated rats. Treatment of 5/6-nephrectomized rats with TCV-116 or manidipine significantly decreased glomerular expression of alpha-smooth muscle actin and desmin, thereby indicating that these drugs prevented glomerular phenotypic changes in 5/6-nephrectomized rats. Furthermore, their inhibitory effects on glomerular phenotypic modulation were associated with the prevention of glomerular cell proliferation, hypertrophy, and sclerosis. Therefore, this study provides the first evidence that the renoprotection is linked to the prevention of glomerular phenotypic modulation and supports the idea that this phenotypic modulation may serve as an important cellular marker of glomerular injury.
Nodular regenerative hyperplasia of the liver and coeliac disease: potential role of IgA anticardiolipin antibody
Authors: A Austin
Journal: Gut (2004)

Nodular regenerative hyperplasia (NRH) of the liver is a rare disorder that is often associated with connective tissue disorders, haematological malignancy, or drugs, and is a cause of non-cirrhotic portal hypertension. We describe two cases of NRH in individuals with adult coeliac disease and IgA anticardiolipin antibodies. We discuss the potential impact of this observation on the understanding of the pathogenesis of NRH.
Titrated oxygen requirement and prognostication in idiopathic pulmonary fibrosis
Authors: J.L. Hook, S.M. Arcasoy, D. Zemmel, M.N. Bartels, S.M. Kawut, D.J. Lederer
Journal: European Respiratory Journal (2011)

The supplemental oxygen flow rate is a common bedside measure of gas exchange impairment. We aimed to determine whether a titrated oxygen requirement (TOR) predicted mortality in idiopathic pulmonary fibrosis (IPF). We examined 104 adults with IPF enrolled in a prospective cohort study and a validation cohort of 151 adults with a variety of interstitial lung diseases (ILDs). The TOR was defined as the lowest oxygen flow rate required to maintain an oxyhaemoglobin saturation of 96% while standing. Cox proportional hazards models and time-dependent receiver operating characteristic curves were used to examine survival time. A higher TOR was associated with a greater mortality rate independent of forced vital capacity and 6-min walk test results in IPF (adjusted hazard ratio (per 1 L·min −1 ) 1.16, 95% CI 1.06–1.27). The TOR was at least as accurate as pulmonary function and 6-min walk testing at predicting 1-yr mortality. Findings were similar in other ILDs. The TOR is a simple, inexpensive bedside measurement that aids prognostication in IPF.
Mutated BRAF Emerges as a Major Effector of Recurrence in a Murine Melanoma Model After Treatment With Immunomodulatory Agents
Authors: Shane Zaidi, Miran Blanchard, Kevin Shim, Elizabeth Ilett, Karishma Rajani, Christopher Parrish, Nicolas Boisgerault, Tim Kottke, Jill Thompson, Esteban Celis, Jose Pulido, Peter Selby, Hardev Pandha, Alan Melcher, Kevin Harrington, Richard Vile
Journal: Molecular Therapy (2014)

We used a VSV-cDNA library to treat recurrent melanoma, identifying immunogenic antigens, allowing us to target recurrences with immunotherapy or chemotherapy. Primary B16 melanoma tumors were induced to regress by frontline therapy. Mice with recurrent tumors were treated with VSV-cDNA immunotherapy. A Th17 recall response was used to screen the VSV-cDNA library for individual viruses encoding rejection antigens, subsequently targeted using immunotherapy or chemotherapy. Recurrent tumors were effectively treated with a VSV-cDNA library using cDNA from recurrent B16 tumors. Recurrence-associated rejection antigens identified included Topoisomerase-IIα, YB-1, cdc7 kinase, and BRAF. Fourteen out of 16 recurrent tumors carried BRAF mutations (595-605 region) following frontline therapy, even though the parental B16 tumors were BRAF wild type. The emergence of mutated BRAF-containing recurrences served as an excellent target for BRAF-specific immune-(VSV-BRAF), or chemo-(PLX-4720) therapies. Successful PLX-4720 therapy of recurrent tumors was associated with the development of a broad spectrum of T-cell responses. VSV-cDNA technology can be used to identify recurrence specific antigens. Emergence of mutated BRAF may be a major effector of melanoma recurrence which could serve as a target for chemo or immune therapy. This study suggests a rationale for offering patients with initially wild-type BRAF melanomas an additional biopsy to screen for mutant BRAF upon recurrence.
Lung function in healthy never smoking adults: reference values and lower limits of normal of a Swiss population.
Authors: O Brandli, C Schindler, N Kunzli, R Keller, A P Perruchoud
Journal: Thorax (1996)

BACKGROUND: Reference values and definitions of "normal" are prerequisites for population screening and classification of lung diseases. The aim of this study was to calculate reference values for never smoking Caucasian adults. METHODS: In the SAPALDIA cross sectional study respiratory health was assessed in a random sample of 9651 subjects, aged 18-60 years, from eight areas of Switzerland. Lung function was measured according to ATS criteria including quality control. In 3157 healthy never smoking adults without respiratory symptoms the mean values and fifth percentiles of lung function variables were calculated. For each sex, logarithms of lung function were regressed against age, age squared, and the logarithm of height. Residuals were used to estimate fifth percentiles across the age range using a technique not requiring normality or homoscedasticity of residuals. RESULTS: Most lung function variables were non-linear with age and showed an increase in early adulthood and an accelerated decline thereafter. The reference values for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were higher than those of the European Community for Coal and Steel and those from North America. The prediction equations for lower fifth percentile values defined a stable proportion of subjects outside this limit whereas alternative methods for estimating the fifth percentile showed a loss of sensitivity with age. CONCLUSIONS: The reference equations for mean values of spirometric indices and their lower fifth percentiles gave an improved and unbiased lower limit of normal. The higher mean values may in part be due to the strictly selected population, quality control procedures, cohort effects, and altitude, and are not explained by the statistical model used.
Turning over a new leaf in plant genomics
Authors: Mario Caccamo, Erich Grotewold
Journal: Genome biology (2013)

Plant species have adapted to most of the planet’s eco­ systems, off ering an amazing range of traits, behaviors and morphologies. Unlocking the underlying mecha­ nisms for this diversity is providing novel insights into the molecular hardwiring of plants and how they interact with their environment, furnishing new opportunities to develop better and more sustainable crops. Access to fast and inexpensive sequencing and advances in compu­ tational methods, coupled with an increasing demand for food and fuel crops, have provided the basis for the current revolution in plant genomics. Th e development of agriculture and the ability to store food laid the foundations of early human civilizations and defi ned modern society very much as we understand it today. Arguably, the domestication of small grain crops over the past 10,000 years ranks as one of the most important events in human history. Th e co­evolution of humans and plants, however, goes back to the origins of the primate lineage. One example is the expansion of hominids, which some authors correlate with the direct adoption in the diet of C 4 plants, or indirectly by preying on animals that consumed C 4 plants [1]. Th e development of salivary amylase, key in the digestion of starch, which emerged as a gene family expansion independently in primates and rodents, provides another example. Th e number of copies of the amylase genes is highly variable in human populations with diff erent starch diets [2]. But it is not only about food: ficrops provided clothes and paper; wood from trees became material for shelters, and until the discovery of fossil fuels, was one of the most important sources of energy. We have also used plant extracts as a source of medicines and other useful bio­ chemicals that in many cases cannot yet be synthesized in the laboratory. Plants also have a direct impact on our environment: as autotrophs they are responsible for fiatmospheric carbon into food and fi ber, with
Primary coliform peritonitis in an adult.
Authors: B. T. Jackson
Journal: BMJ (1970)

Primary (idiopathic) peritonitis is an uncommon condition that typically occurs in prepubertal girls and is either pneumococcal or streptococcal in origin.Adult cases are rare and a coliform origin is so unusual that Macbeth and MacKenzie (1968) have suggested that this diagnosis is always suspect.The following report is of a case of primary coliform peritonitis in an adult diagnosed at laparotomy and confirmed by necropsy and bacteriology. CASE HISTORYA 56-year-old housewife presented as an emergency case with a history of several hours of severe generalized abdominal pain, maximal in the lower abdomen.The pain was constant and aggravated by movement.She was nauseated but had not
Oral contraception, parity, breast feeding, and severity of rheumatoid arthritis.
Authors: C Jorgensen, M C Picot, C Bologna, J Sany
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To investigate the influence of breast feeding, use of the oral contraceptive pill (OCP), and parity on rheumatoid arthritis (RA). METHODS: One hundred and seventy six women with RA were compared with 145 control subjects; all had at least one child. RA patients were classified as having severe (n = 82) or mild disease (n = 89) according to clinical joint evaluation, radiological score, biological inflammation, and the presence of HLA-DR1 or -DR4 alleles. RESULTS: The mean age of RA patients was 58 years, and the mean age at the time of diagnosis of RA was 46 years. The mean time between onset of RA and the first birth was 23.6 (SD 3.8) years. The OCP user rates were 33% in the RA group and 47.6% in the control group (p &lt; 0.02). OCP use was related to the mother9s year of birth. The relative risk for developing RA was 0.598 (95% confidence interval (CI) 0.33 to 1.1) in women who had used OCP for more than five years compared with those who had never used OCPs. In contrast, the age at which the first pregnancy occurred, the number of children breast fed, and the duration of breast feeding were comparable in RA patients and healthy subjects. Among the RA patients, parity, duration of breast feeding, and the number of breast fed children were significantly increased in those with severe disease. Having more than three children increased the risk of developing severe disease 4.8-fold when adjusted for age and OCP use. Forty six percent of women with severe RA had a history of breast feeding duration greater than six months before disease onset, compared with 26% of patients with mild disease (p &lt; 0.008). Having more than three breast fed children increased the risk of poor disease prognosis 3.7-fold. In contrast, OCP use had a protective role in the course of RA (44% of RA patients with mild disease were OCP users, compared with 21.7% of those with severe RA; p &lt; 0.001). Among those using OCP for more than five years, the relative risk of developing severe disease was 0.1 (95% CI 0.01 to 0.6), after adjustment for age, parity, and breast feeding. CONCLUSION: Our results suggest that parity, and to a lesser extent breast feeding, before RA onset worsened RA prognosis, whereas OCP use had a protective role. Prolactin and oestrogen may have a role in these effects.
Sepsis in children
Authors: A. Plunkett, J. Tong
Journal: BMJ (2015)

#### The bottom line

Sepsis is a clinical syndrome resulting from a dysregulated systemic inflammatory response to infection.1 It is characterised by a generalised pro-inflammatory cascade, which may lead to widespread tissue injury.2 It encompasses a clinical spectrum of severity, including severe sepsis, septic shock, and multi-organ failure.3 Sepsis is a leading cause of morbidity and mortality in children worldwide.4

International consensus guidelines define sepsis as the presence of systemic inflammatory response syndrome plus suspected or proven infection.3 A more pragmatic definition of sepsis has been proposed—that sepsis is a systemic response to infection with the presence of some degree of organ dysfunction.5 This definition is not currently widely accepted, but new criteria are under discussion and due to be published later in the year.

Global data on sepsis in children are incomplete, but it is estimated that infection accounts for most deaths (almost 60%) in children aged under 5 years.4 The World Health Organization has stated that the four big causes of death in children worldwide are infectious diseases: pneumonia (1.9 million deaths/year), diarrhoea (1.6 million deaths/year), malaria (1.1 million deaths/year), and measles (550 000 deaths/year).6

The largest epidemiological reports of the incidence …
Chronic Apoptosis of Vascular Smooth Muscle Cells Accelerates Atherosclerosis and Promotes Calcification and Medial Degeneration
Authors: Murray C.H. Clarke, Trevor D. Littlewood, Nichola Figg, Janet J. Maguire, Anthony P. Davenport, Martin Goddard, Martin R. Bennett
Journal: Circulation Research (2008)

Vascular smooth muscle cell (VSMC) accumulation is implicated in plaque development. In contrast, VSMC apoptosis is implicated in plaque rupture, coagulation, vessel remodeling, medial atrophy, aneurysm formation, and calcification. Although VSMC apoptosis accompanies multiple pathologies, there is little proof of direct causality, particularly with the low levels of VSMC apoptosis seen in vivo. Using a mouse model of inducible VSMC-specific apoptosis, we demonstrate that low-level VSMC apoptosis during either atherogenesis or within established plaques of apolipoprotein (Apo)E(-/-) mice accelerates plaque growth by two-fold, associated with features of plaque vulnerability including a thin fibrous cap and expanded necrotic core. Chronic VSMC apoptosis induced development of calcified plaques in younger animals and promoted calcification within established plaques. In addition, VSMC apoptosis induced medial expansion, associated with increased elastic lamina breaks, and abnormal matrix deposition reminiscent of cystic medial necrosis in humans. VSMC apoptosis prevented outward remodeling associated with atherosclerosis resulting in marked vessel stenosis. We conclude that VSMC apoptosis is sufficient to accelerate atherosclerosis, promote plaque calcification and medial degeneration, prevent expansive remodeling, and promote stenosis in atherosclerosis.
Stimulatory effect of pancreozymin-cholecystokinin on calcium secretion in pancreatic juice of dogs
Authors: H. Goebell, Ch. Steffen, Ch. Bode
Journal: Gut (1972)

In four dogs with a permanent duodenal Thomas fistula the secretion of calcium, sodium, potassium, protein, and two pancreatic enzymes in pancreatic juice was studied. Infusion of secretin led to a decrease in concentration of calcium and of protein with increasing rates of fluid production. Pancreozymin-cholecystokinin was given in single injections superimposed on the secretin-stimulated flow of juice. This hormone stimulated the secretion of both calcium and enzyme protein in a parallel and closely correlated fashion. The secretion of this protein-bound calcium fraction I is assumed to occur in the acinar cell. A calcium fraction II, which was independent of protein secretion and pancreozymin stimulation, was demonstrated in concentrations of about 0·4 to 0·6 m-equiv/l. This fraction is thought to originate in the interstitial fluid. The secretion of two calcium-containing fluids is in accordance with the two-component theory of secretion proposed by Hollander and Birnbaum (1952).
Chronotropic Effects of Norepinephrine and Tyramine: A System Response Analysis
Authors: EDWARD J. BATTERSBY, ELLIOT V. NEWMAN
Journal: Circulation Research (1964)

An analog simulation of the chronotropic effects of norepinephrine and tyramine in the canine heart-lung preparation is presented. The temporal aspects of those responses are described in quantitative terms. Reserpine produced deprivation suprasensitivity to norepinephrine may be considered as a corollary of the system response nonlinearity to that drug. Discrepancies between tyramine rate responses and the relatively small amounts of norepinephrine released are resolved by the assumption that the receptor space for norepinephrine has a capacitative function and is not in free dilutional equilibrium with the perfusing blood. This mechanism would allow for a unitary explanation of tyramine action based upon competition with norepinephrine for available storage sites.
Linezolid: safety and efficacy monitoring
Authors: Mathieu S. Bolhuis, Arianna D. Pranger, Jan-Willem C. Alffenaar
Journal: European Respiratory Journal (2012)

To the Editors:

We read with interest the recent European Respiratory Journal article by Singla et al. [1], which described the treatment outcome of 29 (pre-)extensively drug-resistant (XDR) tuberculosis (TB) patients from Delhi, India. All patients received linezolid as part of their anti-TB regimen. The high percentage of favourable treatment outcomes in the study led Singla et al. [1] to conclude that “Linezolid could have played a key role”. However, in our opinion, conclusions on the role of a single agent, such as linezolid, are difficult to draw from a series of cases without controls, in which every patient received linezolid in addition to an injectable antimycobacterial agent and a fluoroquinolone. Indeed, the important …
Predicting immediate level of care requirement following radical cystectomy – Audit of outcome
Authors: Chrysoula Fragkopoulou, Gavish Munbauhal, Stephen Webber, Sheila M. Reynolds, Ruth Groves, Patrick E. Cutinha, James W.F. Catto, Mark D. Haynes, David R. Yates, Jo Buck, Derek J. Rosario
Journal: International Journal of Surgery (2013)
Suppression of in vivo bile acid synthesis, but not of in vitro cholesterol 7α-hydroxylase expression, by biliary obstruction in humans
Authors: M. Bertolotti, L. Carulli, M. Concari, P. Martella, P. Loria, E. Tagliafico, E. De Fabiani, C. Amorotti, N. Carulli
Journal: Journal of Hepatology (2000)
Successful Pulmonary Thromboendarterectomy in Two Patients with Sickle Cell Disease
Authors: GORDON L. YUNG, RICHARD N. CHANNICK, PETER F. FEDULLO, WILLIAM R. AUGER, KIM M. KERR, STUART W. JAMIESON, DAVID P. KAPELANSKI, KENNETH M. MOSER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Section:ChooseTop of pageAbstract <<CASE REPORT 1CASE REPORT 2DISCUSSIONReferencesCITING ARTICLES
Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte.
Authors: P Brice, Y Bastion, E Lepage, N Brousse, C Haïoun, P Moreau, N Straetmans, H Tilly, I Tabah, P Solal-Céligny
Journal: Journal of Clinical Oncology (1997)

PURPOSE To evaluate prospectively in patients with follicular lymphoma and a low tumor burden three therapeutic options: delay of any treatment until clinically meaningful progression, immediate treatment with an oral alkylating agent, or treatment with a biologic response modifier, interferon alfa-2b. PATIENTS AND METHODS Newly diagnosed follicular lymphoma patients with a low tumor burden (n = 193) were randomly assigned to one of three arms: arm 1, no initial treatment (n = 66); arm 2, prednimustine 200 mg/m2/d for 5 days per month for 18 months (n = 64); or arm 3, interferon alfa 5 MU/d for 3 months then 5 MU three times per week for 15 months (n = 63). Clinical characteristics were similar in the three arms. RESULTS Overall response rates with prednimustine and interferon alfa were 78% and 70%, respectively. The overall response to therapy, when deferred, was similar at 70%. With a median follow-up duration of 45 months after randomization, the median freedom-from-treatment (FFT) interval was 24 months in arm 1 and the interval of freedom from treatment failure (FFTF) was 40 months in arm 2 and 35 months in arm 3. The median overall survival time was not reached and the overall survival rate at 5 years was 78% in arm 1, 70% in arm 2, and 84% in arm 3. Therefore, deferred treatment does not adversely influence survival at 5 years. Patients who progressed within 1 year had a significantly shorter survival duration (median, 48 months). CONCLUSION Delayed treatment is feasible in patients with follicular lymphoma and a low tumor burden. For patients with early progression, more intensive therapy should be considered. For others, because delay of treatment until significant clinical progression does not seem to hamper the prognosis or subsequent response to treatment, the long-term toxicity of alkylating agents can be reduced.