tbuckley/cabot-search huggingface dataset:
High Incidence of Cardiac Malformations in Connexin40-Deficient Mice
Authors: Hong Gu, Frank C. Smith, Steven M. Taffet, Mario Delmar
Journal: Circulation Research (2003)

Gap junctions are intercellular channels formed by oligomerization of a protein called connexin (Cx). The heart expresses at least three connexin isotypes: Cx40, Cx43, and Cx45. A possible role for Cx40 in cardiac morphogenesis remains to be determined. We have characterized the anatomy and histology of fetal and newborn hearts obtained from crossing Cx40-deficient mice of mixed genetic background (C57BL/6x129Sv). Hearts were serial-sectioned (5 microm) along the coronal plane, stained with hematoxylin-eosin, and visualized by conventional light microscopy. Cardiac malformations in mice lacking Cx40 in one allele (Cx40+/-) included bifid atrial appendage, ventricular septal defect, tetralogy of Fallot (TOF), and an aortic arch abnormality. In Cx40-/- mice resulting from crossing of Cx40+/- mice, the most common cardiac malformations were double-outlet right ventricle (DORV), TOF, and endocardial cushion defects. Overall incidence of cardiac malformations was 6/33 (18%) in Cx40+/- mice and 4/12 (33%) in Cx40-/- mice. No cardiac malformations were observed in 15 wild-type mice studied. In addition, we examined 39 hearts from offspring of Cx40-/- matings. Frequency of cardiac malformations was even higher in this group (44%). Over one third of the hearts (14 of 39) showed conotruncal malformations corresponding to either DORV or TOF. Endocardial cushion defects were found in 3 out of 39 hearts. Our results suggest that Cx40 participates in cardiac morphogenesis, likely in association with other (unknown) products whose expression may vary with the genetic background of the mice.
A long-term multicentre assessment of the safety and tolerability of calcitriol ointment in the treatment of chronic plaque psoriasis
Authors: A. LANGNER, P. ASHTON, P.C.M. VAN DE KERKHOF, H. VERJANS
Journal: British Journal of Dermatology (1996)

Calcitriol (1 alpha,25-dihydroxyvitamin D3), applied topically in an ointment base, has been shown to be effective in the treatment of chronic plaque psoriasis. This open study was designed to assess the safety and tolerability of 3 micrograms/g calcitriol ointment applied twice daily over treatment periods of up to 78 weeks. In the 253 evaluable patients with chronic plaque psoriasis no clinically relevant changes were observed in the baseline/end-point analyses of mean serum levels of total calcium, albumin-adjusted total calcium, phosphorus and creatinine, and plasma calcitriol levels. Mean values of 24-h urinary calcium, phosphorus, creatinine and hydroxyproline excretions, creatinine clearance and mean urinary calcium/creatinine ratio also did not show clinically relevant changes in the baseline/end-point analyses. The treatment was well tolerated, with no serious adverse events occurring during the course of the study. Eight patients withdrew from the study due to adverse events which, although not serious, were thought to be treatment-related: in seven patients skin irritation reactions and in one case a transient asymptomatic slight hypercalcaemia was observed. In addition, assessments of global severity, global improvement and Psoriasis Area and Severity Index scores confirmed the therapeutic efficacy of twice daily 3 micrograms/g calcitriol ointment demonstrated in an earlier controlled study. In conclusion, this study demonstrated that twice daily application of 3 micrograms/g calcitriol ointment is safe and well-tolerated in the treatment of chronic plaque psoriasis.
Multicenter phase II trial of docetaxel and carboplatin in patients with stage IIIB and IV non-small-cell lung cancer
Authors: C.P. Belani, A. Einzig, P. Bonomi, T. Dobbs, M.J. Capozzoli, R. Earhart, L.J. Cohen, J.D. Luketich
Journal: Annals of Oncology (2000)
The first year of life. Crying babies.
Authors: H B Valman
Journal: BMJ (1980)

Apart from the subtle method of eye-to-eye communication the baby has { I N EE D no other way of signalling his needs to his mother than by crying.The baby who is quiet or "good" may be abnormal or ill.As crying is a non-specific call for help, obvious needs should be investigated.In most cases no remediable cause is found and the problem may resolve spontaneously when the infant is about 3 months old.By then, however, the parents may have become exhausted from lack of sleep.As well as suggesting any appropriate management, the family doctor should encourage parents to take one or two evenings off together each week to visit friends or go to a film.Sound spectography has confirmed the clinical impression that cries of cerebral irritability, pain, and hunger are different in quality, but this method is not available to most clinicians.During the first month infants do not shed tears when they cry, and even after the age of about 6 ........................... months many infants cry at night without shedding tears. Hunger and thirstBabies often cry and become restless just before a feed is due, and in the ........ X......early weeks of life the infant may demand to be fed three hourly or even two hourly.This is perfectly normal for a breast-fed baby or even a btl-fe bbreivnlo-solute cows' milk preparations.Preterm infants need particularly high milk intakes for "catch-up" growth and they may become less demanding when they reach their final centiles for weight.Mothers who have fed a previous infant with the older full-cream cows' milk preparations may be surprised how often their new babies, fed on the lower-solute milks, want to be fed.......... .............The volumes of bottled milk recommended are only average amounts
Estimation of the Secretion Rate of Thyrotropin in Man*
Authors: W. D. Odell, R. D. Utiger, J. F. Wilber, P. G. Condliffe
Journal: Journal of Clinical Investigation (1967)

The plasma concentration of a pituitary hormone is determined by the rate of secretion, degradation, and the volume of distribution of that hormone. Using a radioimmunoassay for human thyrotropin (TSH) and human TSH-(131)I, we have estimated the rates of degradation and distribution of TSH in man and calculated the rate of secretion. Either 0.5 or 5 mug of TSH-(131)I with specific activities of 1 to 50 muc per mug was administered intravenously to 12 euthyroid subjects. Serial determinations were made of TSH-(131)I, and the half-time of disappearance (t((1/2))) was thus estimated. The average t((1/2)) in euthyroid subjects was 53.9 minutes with a volume of distribution averaging 5.8% of body weight. The mean endogenous plasma TSH concentration was 1.8 mmug per ml (2.7 muU per ml in terms of the human TSH reference standard A). The mean total TSH pool, excluding the pituitary, was 5.8 mug (8.7 mU). From these data the mean secretion rate of TSH in euthyroid man was calculated to be 110.1 mug per day (165.2 mU). Similar data were estimated for 3 mildly hypothyroid patients. The t((1/2)) were 75.1, 97.1, and 83.6 minutes, with a mean of 85.3 minutes (1.6 times normal). The mean TSH pool was 58.1 mug (10 times normal). The secretion rate was 688.7 mug per day (1,033.1 mU). In other hypothyroid patients, plasma TSH levels ranging from 6 to 230 mmug per ml (9 to 345 muU) have been found. If similar half-times and a normal distribution volume are assumed, the secretion rate of TSH in hypothyroid patients can be estimated to range from about 260 to 15,350 mug per day (390 to 23,025 mU) or from about 2 to 307 times normal. Therefore, the elevated plasma TSH levels found in hypothyroidism are a result of both slower degradation and increase in rate of secretion.
Inhibition of myeloperoxidase by synovial fluid and serum.
Authors: B Dularay, C M Yea, C J Elson
Journal: Annals of the Rheumatic Diseases (1991)

An inhibitor of myeloperoxidase has been identified in the synovial fluids and sera from patients with rheumatoid arthritis and sera from normal subjects. Initially, these fluids were found to inhibit stimulus induced degranulation of polymorphonuclear leucocytes independently of the stimulating agent. Subsequently, the fluids were shown to inhibit the released enzyme rather than the degranulation response of polymorphonuclear leucocytes. Both rheumatoid and normal serum samples contained high concentrations of the inhibitor but the concentrations were lower in rheumatoid synovial fluids. The inhibitory activity seemed to be specific for peroxidase as the fluids did not inhibit beta-glucuronidase activity. A protein of relative molecular mass (Mr) 150 kd was purified from synovial fluid by affinity chromatography on myeloperoxidase-Sepharose. It is concluded that serum and synovial fluid contain a novel myeloperoxidase inhibitor, which acts by binding to myeloperoxidase and thereby prevents myeloperoxidase releasing oxidative products in serum.
Osteonecrosis of the Jaw and Oral Health–Related Quality of Life After Adjuvant Zoledronic Acid: An Adjuvant Zoledronic Acid to Reduce Recurrence Trial Subprotocol (BIG01/04)
Authors: Emma J. Rathbone, Janet E. Brown, Helen C. Marshall, Michelle Collinson, Victoria Liversedge, Geraldine A. Murden, David Cameron, Richard Bell, Saiqa Spensley, Rajiv Agrawal, Rema Jyothirmayi, Prabir Chakraborti, Frances Yuille, Robert E. Coleman
Journal: Journal of Clinical Oncology (2013)

In patients with early breast cancer, adjuvant zoledronic acid (zoledronate) may reduce recurrence and improve survival. However, zoledronate is associated with the occasional development of osteonecrosis of the jaw (ONJ). We report on the frequency of ONJ and investigate oral health-related quality of life (Oral-QoL) in a large randomized trial (Adjuvant Zoledronic Acid to Reduce Recurrence [AZURE]).Three thousand three hundred sixty women with stage II or III breast cancer were randomly assigned to receive standard adjuvant systemic therapy alone or with zoledronate administered at a dose of 4 mg for 19 doses over 5 years. All potential occurrences of ONJ were reported as serious adverse events and centrally reviewed. Additionally, we invited 486 study participants to complete the Oral Health Impact Profile-14 (OHIP-14) to assess Oral-QoL around the time the patients completed 5 years on study. Multivariable linear regression was used to calculate mean scores and 95% CIs in addition to identifying independent prognostic factors.With a median follow-up time of 73.9 months (interquartile range, 60.7 to 84.2 months), 33 possible cases of ONJ were reported, all in the zoledronate-treated patients. Twenty-six cases were confirmed as being consistent with a diagnosis of ONJ, representing a cumulative incidence of 2.1% (95% CI, 0.9% to 3.3%) in the zoledronate arm. Three hundred sixty-two patients (74%) returned the OHIP-14 questionnaire. Neither the prevalence nor severity of impacts on Oral-QoL differed significantly between zoledronate patients and control patients.Adjuvant zoledronate used in the intensive schedule studied in the AZURE trial is associated with a low incidence of ONJ but does not seem to adversely affect Oral-QoL.
Morphology and pathogenesis of desquamative interstitial pneumonitis.
Authors: E Valdivia, G Hensley, E P Leory, J Wu, W Jaeschke
Journal: Thorax (1977)

Thirty human lung biopsy specimens have been diagnoses as desquamative interstitial pneumonitis. Six cases had intraalveolar lesions, believed to be early, while 20 had advanced disease characterised by intraalveolar cellular clumps, alveolar wall fibrosis, distortion, and loss of pulmonary parenchyma. Electron microscopy, high resolution light microscopy, and cytological examination have shown that the characteristic clumps in the alveolar air spaces are formed predominantly by enlarged and aggregated macrophages. Lymphocytes and eosinophils are also present in the intraalveolar clumps and in alveolar walls. Inflammation and immunological mechanisms are suggested as causes of the cellular clumping. Interstitial pneumonitis, alveolar wall fibrosis, changes in the alveolar epithelium, and loss of lung parenchyma are believed to be secondary events.
Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy
Authors: A Kamischke, DE Kemper, MA Castel, M Luthke, C Rolf, HM Behre, H Magnussen, E Nieschlag
Journal: European Respiratory Journal (1998)

Under the clinical impression that patients with chronic obstructive pulmonary disease (COPD) may demonstrate signs compatible with hypogonadism, we investigated whether oral glucocorticoid therapy is associated with testosterone deficiency. Thirty six men with COPD of whom 16 were receiving oral glucocorticoid medication (mean+/-SEM dose 9.4+/-1.1 mg prednisolone) were investigated in a cross-sectional cohort study. Patients with or without oral glucocorticoid therapy were not different in terms of age, smoking history and additional therapy. Vital capacity, forced expiratory volume in one second, airway resistance, intrathoracic gas volume and blood gases at rest were not different between the groups. However, patients receiving glucocorticoids had a shorter 6 min walking distance (mean+/-SEM 205+/-27 versus 288+/-26 m; p=0.02) compared to patients without oral steroid therapy. Serum levels of testosterone (mean+/-SEM 13.7+/-0.9) were below normal (&lt;12 nM) in 15 of 36 patients. Serum testosterone did not correlate with any other evaluated parameter. Serum levels of free testosterone (free T) (mean+/-SEM 172.3+/-7.8 pM) were decreased in 25 of the 36 patients, including all patients receiving glucocorticoid treatment. In the 16 patients taking glucocorticoids free T was correlated (p=0.016) with the current glucocorticoid dosage (r=-0.504; p=0.007) and the body mass index (r=0.241; p=0.037). All other parameters examined revealed no significant correlations in multiple regression analysis. Glucocorticoid treatment appears to aggravate hypogonadism and a therapeutic study using testosterone in patients with chronic obstructive pulmonary disease receiving glucocorticoid medication appears warranted.
Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease
Authors: R. M. Gadaleta, K. J. van Erpecum, B. Oldenburg, E. C. L. Willemsen, W. Renooij, S. Murzilli, L. W. J. Klomp, P. D. Siersema, M. E. I. Schipper, S. Danese, G. Penna, G. Laverny, L. Adorini, A. Moschetta, S. W. C. v. Mil
Journal: Gut (2011)

<h3>Background &amp; aims</h3> Inflammatory bowel disease (IBD) is characterised by chronic intestinal inflammation, resulting from dysregulation of the mucosal immune system and compromised intestinal epithelial barrier function. The bile salt, nuclear farnesoid X receptor (FXR), was recently implicated in intestinal antibacterial defence and barrier function. The aim of this study was to investigate the therapeutic potential of FXR agonists in the treatment of intestinal inflammation in complementary in vivo and in vitro models. <h3>Methods</h3> Colitis was induced in wild-type (WT) and <i>Fxr-null</i> mice using dextran sodium sulfate, and in WT mice using trinitrobenzenesulfonic acid. Mice were treated with vehicle or the FXR agonist INT-747, and colitis symptoms were assessed daily. Epithelial permeability assays and cytokine expression analysis were conducted in mouse colon and enterocyte-like cells (Caco-2/HT29) treated with medium or INT-747. Inflammatory cytokine secretion was determined by ELISA in various human immune cell types. <h3>Results</h3> INT-747-treated WT mice are protected from DSS- and TNBS-induced colitis, as shown by significant reduction of body weight loss, epithelial permeability, rectal bleeding, colonic shortening, ulceration, inflammatory cell infiltration and goblet cell loss. Furthermore, Fxr activation in intestines of WT mice and differentiated enterocyte-like cells downregulates expression of key proinflammatory cytokines and preserves epithelial barrier function. INT-747 significantly decreases tumour necrosis factor α secretion in activated human peripheral blood mononuclear cells, purified CD14 monocytes and dendritic cells, as well as in lamina propria mononuclear cells from patients with IBD. <h3>Conclusions</h3> FXR activation prevents chemically induced intestinal inflammation, with improvement of colitis symptoms, inhibition of epithelial permeability, and reduced goblet cell loss. Furthermore, FXR activation inhibits proinflammatory cytokine production in vivo in the mouse colonic mucosa, and ex vivo in different immune cell populations. The findings provide a rationale to explore FXR agonists as a novel therapeutic strategy for IBD.
Angiotensin Receptor Blockade With Candesartan Attenuates Atherosclerosis, Plaque Disruption, and Macrophage Accumulation Within the Plaque in a Rabbit Model
Authors: Michael T. Johnstone, Alexandra S. Perez, Imad Nasser, Robert Stewart, Anand Vaidya, Fawaz Al Ammary, Ben Schmidt, Gary Horowitz, Jennifer Dolgoff, James Hamilton, William C. Quist
Journal: Circulation (2004)

Little is known about whether direct angiotensin receptor blockade can reduce atherosclerosis and plaque disruption. This study evaluated the effect of angiotensin receptor blockade on both the development of atherosclerosis and the disruption of plaque in a modified Constantinides animal model.Twenty-eight New Zealand White rabbits underwent aortic balloon injury followed by a 1% cholesterol diet for 8 weeks. Thirteen rabbits received candesartan at 0.5 mg x kg(-1) x d(-1) beginning 2 days before aortic balloon injury and continued for the total 8 weeks of the cholesterol diet. The rabbits were then pharmacologically triggered and humanely killed, and their aortas were analyzed. The degree of atherosclerosis was determined by intima-media ratio of the infrarenal portion of the aorta. The frequency of intra-aortic thrombosis, a measure of plaque disruption, and the percentages of macrophage area and collagen-staining area of the plaque were determined. Candesartan-treated rabbits had less atherosclerosis (intima-media infrarenal aorta ratio of 1.18+/-0.08 versus 1.57+/-0.08 [mean+/-SEM] for the placebo group, P<0.001); fewer thrombi (3 of 13 versus 11 of 15; P<0.05); lower percentage area of macrophages to total plaque (18.8+/-2.7% versus 27+/-2.5%, P<0.05); and higher collagen to total plaque area (45+/-3% versus 35+/-2%, P<0.01).These results demonstrate that angiotensin receptor blockade attenuates the degree of atherosclerosis and reduces both plaque disruption and macrophage accumulation while increasing collagen deposition in the aortas of this animal model.
Clinical and prognostic significance of histamine monitoring in patients with CML during treatment with imatinib (STI571)
Authors: H. Agis, W.R. Sperr, S. Herndlhofer, H. Semper, H. Pirc-Danoewinata, O.A. Haas, C. Mannhalter, H. Esterbauer, K. Geissler, C. Sillaber, U. Jäger, P. Valent
Journal: Annals of Oncology (2007)
Comparative Studies of Purified Su bviral Component Vaccines and Formalin-Treated Mammary Tumor Viruses From Four Inbred Strains of Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A J Girardi, A S Dion, A A Pomenti, J A Holben
Journal: JNCI Journal of the National Cancer Institute (1985)

Formalin-treated virus vaccines were prepared from purified murine mammary tumor viruses (MuMTV) from 4 inbred strains of mice: RIII/Imr, GR/Imr, C3H/Imr, and A/Imr. In addition, subviral components were isolated from these 4 strains and purified to homogeneity. The inactivated viruses, their major envelope glycoproteins (gp50-gp55), and their major internal core protein (p28) were emulsified in complete Freund's adjuvant and used as vaccines for prevention of mammary tumors in mice. All 4 Formalin-treated virus vaccines reduced significantly the incidence of mammary tumors in "virus-free" C57BL and BALB/c mice when inoculated prior to challenge with live MuMTV. The RIII-, GR-, and A-MuMTV strains showed extensive heterologous cross-protection, whereas the C3H-MuMTV strain showed significant protection only against C3H- and A-MuMTV challenge. The major viral glycoproteins gp50-gp55 reduced significantly the tumor incidence when mice were challenged with isologous infectious virus after immunization, although these glycoproteins showed different degrees of cross-protection than did the same virus strains used as "intact" but Formalin-treated preparations. RIII-gp55 and GR-gp55 cross-protected against each other but not against challenge with C3H- and A-MuMTV strains; the A-gp50 protected against challenge with A- and RIII-MuMTV strains; C3H-gp55 demonstrated limited activity against C3H-MuMTV challenge only. The internal viral core proteins (p28) were ineffective in all systems studied. The same vaccines were tested in MuMTV-positive, high-tumor-incidence strains from which they were derived. At best, the appearance of spontaneous tumors was delayed in a few experimental sets; eventually, all mice developed mammary tumors. The foster-nursed C3HfC57BL strain of mice, which is not exposed to exogenous MuMTV during suckling and which develops mammary tumors after activation of the endogenous virus genome later in life, was responsive only when the heterologous GR-MuMTV Formalin-treated vaccine was used. The association between the ability of virus vaccines to protect a mouse strain and the degree of natural virus expression in that strain is discussed.
The Persistently Troublesome Cough
Authors: Richard S. Irwin, J. Mark Madison
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Over the past 25 years, a great deal has been learned about the management of cough (1); this information has been summarized recently in an evidence-based consensus panel report primarily written for cough specialists (2) that includes diagnostic algorithms for chronic cough and in a practical review article primarily directed at primary care physicians (3) that includes specific evidence-based recommendations for drug therapy and its dosing. When investigators have faithfully followed diagnostic and treatment protocols that have been shown to be successful, the cause of chronic cough has been determined 88 to 100% of the time, leading to successful therapy in 84 to 98% of the patients. Multiple studies have shown that in approximately 95% of cases involving immunocompetent patients, chronic cough results from postnasal drip syndrome, asthma, gastroesophageal reflux disease (GERD), chronic bronchitis due to cigarette smoking or other irritants, bronchiectasis, eosinophilic bronchitis, or the use of an angiotensin-converting enzyme inhibitor (2). In the remaining 5% of cases, chronic cough is caused by a variety of other diseases, such as bronchogenic carcinoma, metastatic carcinomatosis, sarcoidosis, left ventricular failure, tuberculosis, and aspiration due to pharyngeal dysfunction. A more comprehensive listing of causes has been reviewed elsewhere (4). The focus of this commentary is on the management of the adult immunocompetent patient who has a persistently troublesome cough for a duration of at least 2 months. Because, by definition, the so-called postinfectious cough resolves spontaneously within 2 months (2), that diagnosis is not considered herein. However, when a respiratory infection precedes the development of chronic cough, it is presumed that the infection led to or exacerbated other conditions commonly causing chronic cough, such as postnasal drip syndrome, symptomatic asthma, and GERD.
Relationship between right ventricular volumes measured by cardiac magnetic resonance imaging and prognosis in patients with chronic heart failure
Authors: Christos V. Bourantas, Huan P. Loh, Thanjavur Bragadeesh, Alan S. Rigby, Elena I. Lukaschuk, Scot Garg, Ann C. Tweddel, Farqad M. Alamgir, Nikolay P. Nikitin, Andrew L. Clark, John G.F. Cleland
Journal: European Journal of Heart Failure (2010)