tbuckley/cabot-search huggingface dataset:
Induction of myocardial insulin-like growth factor-I gene expression in left ventricular hypertrophy.
Authors: T J Donohue, L D Dworkin, M N Lango, K Fliegner, R P Lango, J A Benstein, W R Slater, V M Catanese
Journal: Circulation (1994)

BACKGROUND Left ventricular hypertrophy is a generalized adaptation to increased afterload, but the growth factors mediating this response have not been identified. To explore whether the hypertrophic response was associated with changes in local insulin-like growth factor-I (IGF-I) gene regulation, we examined the induction of the cardiac IGF-I gene in three models of systolic hypertension and resultant hypertrophy. METHODS AND RESULTS The model systems were suprarenal aortic constriction, uninephrectomized spontaneously hypertensive rats (SHR), and uninephrectomized, deoxycorticosterone-treated, saline-fed rats (DOCA salt). Systolic blood pressure reached hypertensive levels at 3 to 4 weeks in all three systems. A differential increase in ventricular weight to body weight (hypertrophy) occurred at 3 weeks in the SHR and aortic constriction models and at 4 weeks in the DOCA salt model. Ventricular IGF-I mRNA was detected by solution hybridization/RNase protection assay. IGF-I mRNA levels increased in all three systems coincident with the onset of hypertension and the development of ventricular hypertrophy. Maximum induction was 10-fold over control at 5 weeks in the aortic constriction model, 8-fold at 3 weeks in the SHR, and 6-fold at 6 weeks in the DOCA salt model. IGF-I mRNA levels returned to control values by the end of the experimental period despite continued hypertension and hypertrophy in all three systems. In contrast, ventricular c-myc mRNA content increased twofold to threefold at 1 week and returned to control levels by 2 weeks. Ventricular IGF-I receptor mRNA levels were unchanged over the time course studied. The increased ventricular IGF-I mRNA content was reflected in an increased ventricular IGF-I protein content, as determined both by radioimmunoassay and immunofluorescence histochemistry. CONCLUSIONS We conclude that (1) hypertension induces significant increases in cardiac IGF-I mRNA and protein that occur coordinately with its onset and early in the development of hypertrophy, (2) IGF-I mRNA levels normalize as the hypertrophic response is established, (3) in comparison to IGF-I, both c-myc and IGF-I receptor genes are differentially controlled in experimental hypertension. These findings suggest that IGF-I may participate in initiating ventricular hypertrophy in response to altered loading conditions. The consistency of these findings in models of high-, moderate-, and low-renin hypertension suggests that they occur independently of the systemic renin-angiotensin endocrine axis.
Acetaminophen and diphenhydramine as premedication for platelet transfusions: A prospective randomized double‐blind placebo‐controlled trial
Authors: Stephen E Wang, Primo N. Lara, Angie Lee‐Ow, Jeanne Reed, Lori R. Wang, Patti Palmer, Joseph M. Tuscano, Carol M. Richman, Laurel Beckett, Ted Wun
Journal: American Journal of Hematology (2002)

Abstract Non‐hemolytic transfusion reactions (NHTR) occur in up to 30% of patients receiving platelet transfusions. Premedication with acetaminophen and diphenhydramine is a common strategy to prevent NHTR, but its efficacy has not been studied. In this prospective trial, transfusions in patients receiving pre‐storage leukocyte‐reduced single‐donor apheresis platelets (SDP) were randomized to premedication with either acetaminophen 650 mg PO and diphenhydramine 25 mg IV, or placebo. Fifty‐one patients received 98 transfusions. Thirteen patients had 15 NHTR: 15.4% (8/52) in the treatment arm and 15.2% (7/46) in the placebo arm. Premedication prior to transfusion of pre‐storage leukocyte reduced SDP does not significantly lower the incidence of NHTR as compared to placebo. Am. J. Hematol. 70:191–194, 2002. © 2002 Wiley‐Liss, Inc.
Asthma deaths in Cardiff 1963-74: 53 deaths in hospital.
Authors: J B MacDonald, E T MacDonald, A Seaton, D A Williams
Journal: BMJ (1976)

In a study of factors associated with death from bronchial asthma in hospital 53 patients were investigated.Typically the fatal attack persisted for several days before admission to hospital and normally occurred in patients with a long history of asthma.The patient or doctor often underestimated the severity of the attack.On admission most patients were severely ill, and over a third died within 24 hours.Peak flow rate and blood gases were rarely measured.Corticosteroid treatment was often underused, and patients rarely received assisted ventila- tion before death.Infection played a part in 14 deaths, five of them associated with assisted ventilation.Admitting asthmatics to a special respiratory ward with facilities for standardised assessment and treatment and introducing a self-admission service may help to prevent some of these deaths. MethodsData on every death in hospital in the Cardiff area mentioning "asthma" were collected shortly after the death as detailed previously.'
Metalloproteinase-2 and -9 in Giant Cell Arteritis
Authors: Alicia Rodríguez-Pla, Josep A. Bosch-Gil, José Rosselló-Urgell, Pere Huguet-Redecilla, John H. Stone, Miquel Vilardell-Tarres
Journal: Circulation (2005)

Background— Both matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) have been postulated to play roles in the pathophysiology of giant cell arteritis (GCA) because of their ability to degrade elastin. Understanding the specific mediators of arterial damage in GCA could lead to new therapeutic targets in this disease. Methods and Results— Temporal artery biopsy specimens were obtained from 147 consecutive patients suspected of GCA. Clinical and histopathological data were collected according to protocol. Using immunohistochemistry, we compared the expression of MMP-2 and MMP-9 in the temporal artery biopsies of both GCA cases (n=50) and controls (n=97). MMP-9 was found more frequently in positive than in negative temporal artery biopsies (adjusted odds ratio [OR], 3.20; P =0.01). In contrast, the frequency of MMP-2 was not significantly different between positive and negative biopsies (adjusted OR, 2.18; P =0.22). Both MMP-2 and MMP-9 were found in macrophages and giant cells near the internal elastic lamina and in smooth muscle cells and myofibroblasts of the media and intima. MMP-9 was also found in the vasa vasorum. MMP-9 but not MMP-2 was associated with internal elastic lamina degeneration, intimal hyperplasia, and luminal narrowing, even after adjustment for possible confounding variables. Conclusions— MMP-9 appears more likely than MMP-2 to be involved in the pathophysiology of GCA. MMP-9 not only participates in the degradation of elastic tissue but also is associated with intimal hyperplasia, subsequent luminal narrowing, and neoangiogenesis. The expression of MMP by smooth muscle cells implicates these cells as potential secretory cells in GCA.
Insight on the fate of CNS-targeted nanoparticles. Part II: Intercellular neuronal cell-to-cell transport
Authors: Giovanni Tosi, Antonietta Vilella, Resham Chhabra, Michael J. Schmeisser, Tobias M. Boeckers, Barbara Ruozi, Maria Angela Vandelli, Flavio Forni, Michele Zoli, Andreas M. Grabrucker
Journal: Journal of Controlled Release (2014)
OC-088 IGE sensitisation to food and inhalant allergens in UK adults with EOE: a pilot study
Authors: J O Hayat, I J Skypala, S J Till, J Y Kang
Journal: Gut (2012)

<h3>Introduction</h3> Food and inhalant allergens have been implicated as triggers of eosinophilic oesophagitis (EoE). Although topical steroid therapy remains the mainstay of treatment in adults, elemental and six food elimination diets have been shown to decrease oesophageal eosinophilia and improve symptoms in children and more recently in adults. Limited data in North American adult EoE patients suggests that food allergens commonly associated with IgE sensitisation are peanut, egg and soy. We hypothesised that IgE sensitisation to foods and/or cross-reactive inhalant allergens plays a role in EoE. To test the hypothesis we designed a pilot study to explore possible relationships between IgE sensitisation to food/inhalant allergens and EoE in a UK adult population. <h3>Methods</h3> Ten adult patients with biopsy-proven EoE (&gt;15 eosinophils/HPF) but no previously documented food allergy were included. Participants completed food allergy and dysphagia questionnaires, and underwent skin prick testing (SPT) to a battery of inhalant allergens: timothy grass, birch, six grasses, three trees, plane, mugwort, ragweed, <i>Alternaria</i>, <i>Cladosporium</i>, <i>Aspergillus</i>, house dust mite (HDM) and latex. Foods tested were milk, egg, prawn and cod and plant-derived foods: peanut, hazelnut, sesame, soy, mustard, corn, wheat, barley, celery, raw potato, apple, peach, grape, orange, tomato, melon, kiwi and strawberry. All SPT9s were performed in the presence of positive (histamine) and negative (saline) controls. A wheal size 3 mm or more than the negative control was considered positive. <h3>Results</h3> Of the 10 subjects (7 m, median age 33 years, range 26–52) who completed the study, eight reported dysphagia to solids nine times or more in the previous month. Two patients had required hospital admission in the previous month. Nine subjects identified one or more specific foods as a trigger for symptoms. The most commonly cited foods that were thought to trigger symptoms were meat (lamb or chicken) in four, nuts in three and citrus fruits or apples in three. Nine subjects had positive skin tests to both grass pollen and HDM; four of these subjects also had positive tests to at least three other inhalant allergens. These four subjects had the highest number of positive skin tests to foods (median of 9).The most common positive food SPTs were barley (7), wheat (5) and potato (4). <h3>Conclusion</h3> The high prevalence of IgE sensitisation to foods in this pilot study supports our hypothesis that this plays a role in adult EoE pathophysiology. The high rates of barley and wheat sensitisation raise the possibility of IgE crossreactivity with homologous plant allergens in EoE, notably grass pollen. Further larger studies will be needed to confirm and investigate the significance of these findings. <h3>Competing interests</h3> None declared.
Function and structure in the diphenylamine-exposed kidney.
Authors: K D Gardner, S Solomon, W W Fitzgerrel, A P Evan
Journal: Journal of Clinical Investigation (1976)

Standard micropuncture and microdissection techniques were used to examine the function and structure of nephrons in rats whose kidneys were made cystic by dietary exposure to diphenylamine. Heterogeneity characterized the lesion, with dilation and frank cyst formation occurring in 5-30% of nephrons. Elevated intraluminal hydrostatic pressures, occurring in the absence of increased glomerular filtration or decreased net water reabsorption, were recorded in dilated, but not in nondilated nephrons. Structural studies demonstrated communication of dilated nephrons with cysts, concretions of debris within tubular lumens, evidence of extrinsic pressure by cysts on adjacent tubules, and apparent luminal narrowing of some proximal tubules. These observations were used to explain prolonged loop of Henle transit times and occasional failure to detect [3H]inulin excretion after microperfusion into dilated tubules. It was concluded that the elevated hydrostatic pressures in the dilated nephrons of diphenylamine-exposed kidneys were the consequence of variably severe and frequently incomplete tubular occlusion. These findings support the hypothesis that cyst formation is a consequence of partial obstruction and elevated intratubular pressure in this model and perhaps in other susceptible mammalian kidneys.
Hand Deformities in Rheumatoid Disease
Authors: D. A. Brewerton
Journal: Annals of the Rheumatic Diseases (1957)

Gemfibrozil has been suggested as a sensitive cytochrome P450 2C8 (CYP2C8) inhibitor for clinical investigation by the U.S. Food and Drug Administration and the European Medicines Agency. However, gemfibrozil drug-drug interactions (DDIs) are complex; its major circulating metabolite, gemfibrozil 1-<i>O</i>-<i>β</i>-glucuronide (Gem-Glu), exhibits time-dependent inhibition of CYP2C8, and both parent and metabolite also behave as moderate inhibitors of organic anion transporting polypeptide 1B1 (OATP1B1) in vitro. Additionally, parent and metabolite also inhibit renal transport mediated by OAT3. Here, in vitro inhibition data for gemfibrozil and Gem-Glu were used to assess their impact on the pharmacokinetics of several victim drugs (including rosiglitazone, pioglitazone, cerivastatin, and repaglinide) by employing both static mechanistic and dynamic physiologically based pharmacokinetic (PBPK) models. Of the 48 cases evaluated using the static models, about 75% and 98% of the DDIs were predicted within 1.5- and 2-fold of the observed values, respectively, when incorporating the interaction potential of both gemfibrozil and its 1-<i>O</i>-<i>β</i>-glucuronide. Moreover, the PBPK model was able to recover the plasma profiles of rosiglitazone, pioglitazone, cerivastatin, and repaglinide under control and gemfibrozil treatment conditions. Analyses suggest that Gem-Glu is the major contributor to the DDIs, and its exposure needed to bring about complete inactivation of CYP2C8 is only a fraction of that achieved in the clinic after a therapeutic gemfibrozil dose. Overall, the complex interactions of gemfibrozil can be quantitatively rationalized, and the learnings from this analysis can be applied in support of future predictions of gemfibrozil DDIs.
P1-06-10: Lobular Breast Cancer and NAC: Combined Results from the NKI and I-SPY 1 Trial.
Authors: RA Mukhtar, E Lips, J Wesseling, C Livasy, C Yau, D Berry, L van't Veer, LA Carey, LJ Esserman, S Rodenhuis, ES Hwang
Journal: Cancer Research (2011)

Abstract Background The benefits of neoadjuvant chemotherapy (NAC) in breast cancer are twofold: allowing breast conservation surgery, and assessment of response. Having pathologic complete response (pCR) predicts improved outcomes. Many have suggested that invasive lobular cancers (ILC) do not respond to NAC as well as invasive ductal cancers (IDC), and recommend against offering NAC in such cases. We previously investigated differences in the response to NAC in ILC and IDC in the I-SPY 1 Trial, and now present findings from a joint analysis with the Netherlands Cancer Institute (NKI). Methods: We combined datasets comprising 676 patients (221 from I-SPY, 455 from NKI) enrolled in NAC trials. Eligible patients had palpable tumors ≥ 3 cm, and underwent serial biopsies, microarray analysis (Agilent 44K for I-SPY and Illumina 6v3 for NKI), and MRI imaging. ILC versus IDC histology was assigned by pathologic appearance, and ILCs were tested for e-cadherin expression and centrally reviewed by a breast pathologist at each site. We performed multivariate logistic regression analyses to assess differences in pCR. We compared intrinsic subtypes, prognostic gene signature expression, and MRI phenotypes. Results: There were 75 ILC and 601 IDC cases. ILCs had lower risk features and were more likely hormone receptor + (Table 1) but there was substantial heterogeneity and many ILC had high risk features. There were fewer T2 (33% versus 48%) but more T3 tumors (59% versus 37%) among the ILCs. Nearly 10% of ILC cases had the basal intrinsic molecular subtype; 22% expressed the activated wound healing signature, and 56% had a high risk 70-gene prognostic signature. While pCR rate was lower in ILCs, adjustment for low risk features showed lobular histology was not an independent predictor of pCR. ILC was less likely to present as a solid mass. 85% of ILC were e-cadherin negative. Conclusions: This combined analysis suggests that the decreased response to NAC in ILC is due to the association between ILC and low risk features. ILC in a clinically high risk setting has a higher proportion of high risk biology in spite of lobular histology. Lobular histology alone should not be used to exclude patients from NAC trials or treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-06-10.
British government's proposals on poorly performing doctors
Authors: R. Smith
Journal: BMJ (1995)

engine.We need a rational national transport policy, which should include making sure that each vehicle pollutes as little as possible, improved and cheaper public transport, and measures to encourage safe walking and cycling.Unrestricted expansion in our use of private cars is not sustainable.Not only must the government act but so must each of us who benefits both from the use of cars and from breathing fresh air.Improving air quality will take time.How do we advise patients in the meantime?We can reassure them that air pollution is not a cause for panic.Patients whose respiratory disorders are made worse during pollution episodes should increase their treatment and make sure that they have adequate supplies.They could be advised to avoid optional visits to polluted cities and not to exercise, particularly in busy streets.Masks are a powerful signal to polluting drivers but probably have little protective effect.While air pollution is a cause for concern and requires action, it is not causing a health crisis.We have, as a society, now started to come to terms with the adverse effects of the internal combustion engine, and this process is likely to gather momentum over the next decade.
Abstract 4780: CD4 T-lymphocyte responses to the human telomerase reverse transcriptase (hTERT) in patients (pts) with advanced non small cell lung cancer (NSCLC)
Authors: Elizabeth Fabre, Aurelie CAZES, Patrice Ravel, Jacques Medioni, Magali Dosset, Emeline Leviennois, Eric Tartour, Guy Meyer, Marc Riquet, Olivier Adotevi
Journal: Cancer Research (2010)

Abstract Background: hTERT is a potential target for cancer immunotherapy because it is highly expressed in tumor cells. To assess the applicability of hTERT-based immunotherapy in NSCLC, we aimed to analyse the natural anti-hTERT CD4 T-lymphocyte responses in advanced NSCLC pts. Methods: We included in a prospective, monocentric study chemonaive NSCLC pts. Pts were required to present stage III or IV tumor, without any immune deficiency or immunosuppressive drug. Before start of chemotherapy, the anti-hTERT T-lymphocyte responses were assessed in whole blood by ELISPOT test. We evaluated the presence or absence of hTERT-specific CD4 T lymphocytes. Thereafter, we analyzed its link with age (&amp;lt; 70 vs. ≥ 70 yrs), ECOG performance status PS (0-1 vs. 2-3), tumoral stage (IIIA vs. IIIb + IV), histological subtype (adenocarcinoma vs. other) and smoking status (never smoker vs. smoker). Statistical analysis was performed using chi-Square or Fischer test. Results: Between February 2008 and October 2009, fifty-one NSCLC pts were included. They presented a stage IIIa (n = 5), IIIb (n = 5) or IV (n = 41) disease. Median age was 66 yrs [39-89]. Nineteen pts presented anti-telomerase CD4 T lymphocytes (37 %); among them we found 14 stage IV (73 %), 13 pts &amp;lt; 70 yrs (68 %), 12 pts with PS 0/1 (63 %), 18 adenocarcinoma/undifferentiated carcinoma (94 %), 13 pts with stable disease/ partial response (68%). Furthermore, all non smokers have anti-telomerase immune response. Conclusions: These preliminary results demonstrate that natural anti-hTERT immune response exists in NSCLC pts, even in case of advanced disease. However the presence of immune response is more frequently found in pts less than 70 yrs with good PS, in non squamous cell carcinoma and in pts with non progressive disease. The study is ongoing to evaluate if baseline anti-hTERT immune response could be used as selection criteria for telomerase vaccination in NSCLC. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4780.
Rethinking WHO guidance: review of evidence for misoprostol use in the prevention of postpartum haemorrhage
Authors: Christina S Chu, Petra Brhlikova, Allyson M Pollock
Journal: Journal of the Royal Society of Medicine (2012)

This article describes and critically appraises clinical trials assessing misoprostol effectiveness in preventing primary postpartum haemorrhage (PPH) in home and community settings in low- and middle-income countries. Of 172 identified studies of misoprostol use in labour only six fulfilled the inclusion criteria. All trials used 600μg misoprostol in the intervention arm; three assessed misoprostol alongside components of active management of the third-stage labour (AMTSL), two used expectant management of labour and one allowed birth attendants to choose management practice. The three AMTSL studies showed no significant differences in PPH incidence or referral to higher centres and only one study showed significant decrease in severe PPH using misoprostol. One expectant management study and the choice of management by birth attendants study found significant decreases in PPH incidence with misoprostol. All studies showed significantly increased risk of shivering with misoprostol. Studies were biased by use of alternative uterotonics in the control arm, confounding management practices, and subjective assessment and, with one exception, exclusion of high-risk women. PPH incidence fell in both the control and intervention groups in both the landmark papers that informed the World Health Organization (WHO) decision to admit misoprostol to the Essential Medicines List. This suggests factors other than misoprostol use are crucial. Current evidence does not support misoprostol use in home and community settings in low- and middle-income countries for PPH prevention. WHO should rethink its recent decision to include misoprostol on the Essential Medicines List.