tbuckley/cabot-search huggingface dataset:
Cross‐reactivity and tolerability of imipenem in patients with delayed‐type, cell‐mediated hypersensitivity to β‐lactams
Authors: D. Schiavino, E. Nucera, C. Lombardo, M. Decinti, L. Pascolini, G. Altomonte, A. Buonomo, G. Patriarca
Journal: Allergy (2009)

Administration of imipenem-cilastatin to patients with IgE-mediated hypersensitivity to beta-lactams has always been considered potentially harmful. Recent studies have demonstrated the tolerability of carbapenems (imipenem-cilastatin and meropenem) in patients with IgE-mediated hypersensitivity to beta-lactams; there are no studies on this topic regarding patients with cell-mediated allergy to beta-lactams. The aim of this study is to assess cross-reactivity and tolerability of imipenem in patients with cell-mediated allergy to beta-lactams.From our database we selected 73 patients with cell-mediated allergy to beta-lactams, diagnosed by means of immediate-type skin tests, delayed reading intradermal tests, patch tests and detection of specific IgE. Patients with negative patch tests with imipenem-cilastatin underwent an intramuscular test dosing.Our patients had a total of 94 nonimmediate reactions to penicillins. All patients had positive patch tests and/or delayed reading intradermal tests for at least one of the penicillin reagent tested and negative immediate-type skin tests and specific IgE. Four patients out of 73 had a positive patch tests to at least one penicillin reagent and imipenem-cilastatin showing cross-reactivity. Sixty-four patients underwent the imipenem-cilastatin intramuscular test dosing and none of them had a clinical reaction.Our rate of cross-reactivity between imipenem-cilastatin and other beta-lactams was 5.5%. This result is different from previous findings and this may be explained by the fact that we investigated patients with cell-mediated allergy to beta-lactams. Patients with cell-mediated allergy to beta-lactams should undergo patch tests and a tolerance challenge test before treatment with imipenem-cilastatin.
Social Causes of Coronary Heart Disease
Authors: J. Eyer
Journal: Psychotherapy and Psychosomatics (1980)

By combining the results of prospective and other studies with cross-national and time series analyses of death rates, it is possible to roughly quantify the relative contribution of various causal factors to excess mortality. When coronary heart disease is treated in this way, it is apparent that broad social forces are its main causal factors. Primary among these forces are overwork and various kinds of social disruption. These in turn are at the center of the typical social transformation which accompanies modern economic growth (capitalism).
Abstract 2226: Loss of STAG2 in bladder cancer
Authors: Nithya Krishnan, Anna Woloszynska-Read, Jianmin Wang, Song Liu, Carl Morrison, Khurshid Guru, Evelyn Smit, Donald Trump, Candace Johnson
Journal: Cancer Research (2014)

Abstract Bladder cancer (BC), 90% of which have transitional cell histology, is the fourth most common malignancy in the US. Transitional cell carcinoma (TCC), which occurs predominantly in men and whose incidence appears to be increasing, occurs most frequently as superficial disease which, while prone to recurrence, is not life threatening. However, TCC which invades the muscle layer of the bladder (stage T2-T4) is lethal in ∼50% of individuals. Stage T2-T4 TCC is present at initial diagnosis in ∼30% of patients and superficial TCC progresses to T2-T4 disease 20% of the time. We sequenced whole exomes of 28 muscle-invasive bladder tumors and performed an additional screen of over 200 genes in 119 additional TCCs. We found frequent alterations (10%) in STAG2, a gene encoding a subunit of the cohesin complex, which regulates the sister chromatids segregation process. Most mutations identified on STAG2 were nonsense, missense or frameshift. Genetic disruption of the sister chromatid segregation process leads to aneuploidy, which is one of the hallmarks of cancer. Based on recently published studies, however, it is uncertain whether a loss of STAG2 causes aneuploidy or not. In this study we sought to elucidate the role of STAG2 loss of expression in bladder tumorigenesis. We have analyzed the expression of STAG2 in 14 urothelial cell lines at both mRNA and protein levels by means of q-PCR and western blots, respectively. We found that STAG2 expression was lost in 2 of the 14 urothelial cell lines (HB-CLS-2 and UM-UC-3) analyzed. We chose SV-HUC (immortalized normal urothelium cells) along with two bladder cancer cell lines that had high expression of STAG2 (HB-CLS-1 and TCC-SUP) to study effects of STAG2 loss by transient knockdown. Knockdown of STAG2 in SV-HUC, TCC-SUP and HB-CLS-1 cells did not affect proliferation. Cell cycle analysis on TCC-SUP cells revealed that STAG2 knockdown resulted in a lower percentage of cells in the G0/G1 phase in comparison to the scrambled control. Taken together, these data suggest that STAG2 has a role in modifying DNA content but not proliferation. Our ongoing studies utilizing bladder cancer tissue microarray (TMAs) and copy number variation (CNV) array will help to clarify the consequences of STAG2 loss in bladder cancer. Citation Format: Nithya Krishnan, Anna Woloszynska-Read, Jianmin Wang, Song Liu, Carl Morrison, Khurshid Guru, Evelyn Smit, Donald Trump, Candace Johnson. Loss of STAG2 in bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2226. doi:10.1158/1538-7445.AM2014-2226
When knee pain is not osteoarthritis
Authors: D. Baxter
Journal: BMJ (2009)

Jenkinson and colleagues show that a simple dietary and exercise intervention has positive effects on knee pain.1 Over half of their unselected group, however, did not have radiological evidence of osteoarthritis. This shows that practitioners should always consider intra-articular and periarticular soft tissue problems and referred pain from other musculoskeletal regions. This large …
A novel stimuli-synchronized alloy-treated matrix for space-defined gastrointestinal delivery of mesalamine in the Large White pig model
Authors: Priya Bawa, Yahya E. Choonara, Lisa C. du Toit, Pradeep Kumar, Valence M.K. Ndesendo, Leith C.R. Meyer, Viness Pillay
Journal: Journal of Controlled Release (2012)
Lack of effect of propranolol and metoprolol on glucose tolerance in maturity-onset diabetics.
Authors: K L Woods, A D Wright, M J Kendall, E Black
Journal: BMJ (1980)

Lack of effect of propranolol and metoprolol on glucose tolerance in maturity-onset diabetics Although the effect of beta-blocking drugs on the response to hypoglycaemia has been extensively studied, less attention has been paid to the possibility that they might cause deterioration of glucose tolerance.Release of insulin is stimulated by beta-agonists, and two studies have shown that infusion of propranolol reduces insulin response to a glucose load in normal subjects.1 2 A group of maturity-onset dia- betics tended to have higher blood sugars during chronic treatment with propranolol or the beta-selective agent metoprolol than when receiving placebo.3We report here a controlled study of the effects of these two drugs at two dosage levels on the oral glucose tolerance and insulin response of a group of maturity-onset diabetics.
Unilateral Cervicothoracic Sympathetic Ganglionectomy for the Treatment of Long QT Interval Syndrome
Authors: Arthur J. Moss, Joseph McDonald
Journal: New England Journal of Medicine (1971)

THE syndrome of congenital deafness, syncopal episodes, long QT interval on the electrocardiogram and sudden death has been well described.1 2 3 Recently, ventricular dysrhythmias have been documented as the cause of the syncope and sudden death in this condition.4 Although the original descriptions indicated that the syndrome was hereditable, sporadic, nonfamilial cases with and without associated deafness have been reported.5 The cause of the prolonged QT interval is poorly understood, but abnormalities in the central nervous system have been implicated.6 Effective antiarrhythmic therapy has been the subject of considerable interest since the prolonged QT interval contraindicates the use of most standard . . .
Creatinine content of urine and bacterial growth.
Authors: W. R. Cattell, J. M. Sardeson, E. Hutchinson, F. O'Grady
Journal: BMJ (1969)

759), like myself' and many others, again calls attention to the potential dangers of rhesus isoimmunization in therapeutic abortion.He asks that the extent of this problem be further and scientifically investigated.There are, in fact, one or two further facets to be considered.Firstly, all of us are aware of the numbers of women whose first con- tinuing pregnancy is complicated by rhesus isoimmunization induced by a previous criminal or spontaneous abortion, and it would seem clear that we should include within the scope of an investigation all primi- gravid women who are aborting, whether this be criminal, spontaneous, or therapeutic.Secondly, it has been claimed in some quarters that different techniques of therapeutic abortion carry different risks of rhesus isoimmunization, and this, in addition, should certainly be investigated.Present stocks of anti-D immune globulin are far too low to allow of routine administra- tion to all Rh-negative nulliparous women undergoing abortion, and it is doubtful if stocks would admit of administration to all such women in whom the Kleihauer test is positive.Up to now, therefore, there has been no clinical indication even to do the Rh test on women admitted with complete septic or spontaneous abortion and certainly not to perform the much more complicated and time-consuming Kleihauer test.I fancy that we are once more up against the prob- lem of the peripheral hospitals with large numbers of cases having to preserve their laboratory facilities for real clinical necessity and the central hospitals with adequate laboratory facilities with small numbers of cases unable to obtain statistically significant data without undue delay.-Iam, etc.,
Coactivation of Liver Receptor Homologue-1 by Peroxisome Proliferator-Activated Receptor γ Coactivator-1α on Aromatase Promoter II and Its Inhibition by Activated Retinoid X Receptor Suggest a Novel Target for Breast-Specific Antiestrogen Therapy
Authors: Rachid Safi, Agnes Kovacic, Stéphanie Gaillard, Yoko Murata, Evan R. Simpson, Donald P. McDonnell, Colin D. Clyne
Journal: Cancer Research (2005)

Abstract Aromatase inhibitors target the production of estrogen in breast adipose tissue, but in doing so, also decrease estrogen formation in bone and other sites, giving rise to deleterious side effects, such as bone loss and arthralgia. Thus, it would be clinically useful to selectively inhibit aromatase production in breast. In this regard, we have determined that the orphan nuclear receptor liver receptor homologue-1 (LRH-1) is a specific transcriptional activator of aromatase gene expression in human breast preadipocytes but not in other tissues of postmenopausal women. In this study, we show that the coactivator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a physiologically relevant modulator of LRH-1, and that its transcriptional activity can be inhibited effectively using receptor-interacting peptide antagonists that prevent PGC-1α recruitment. Interestingly, we note that all of these peptides also interact in an agonist-dependent manner with retinoid X receptor α (RXRα), suggesting that these two receptors may compete for limiting cofactors within target cells. In support of this hypothesis, we show that 9-cis-retinoic acid, acting through RXR, inhibits both the basal and PGC-1α–induced transcriptional activity of LRH-1. The importance of this finding was confirmed by showing that LRH-1–dependent, PGC-1α–stimulated regulation of aromatase gene expression in primary human breast preadipocytes was effectively suppressed by RXR agonists. We infer from these data that LRH-1 is a bona fide target whose inhibition would selectively block aromatase expression in breast, while sparing other sites of expression. (Cancer Res 2005; 65(24): 11762-70)
Decreased ascites occurrence in interferon (IFN) treated HCV cirrhosis: results of a survey of a large cohort of interferon treated and untreated patients
Authors: Giancarla Poli, Massimo Pozzi, Alessandro Redaelli, Luigi Roffi, Eliseo Minola, Elena Redaelli, Laura Ratti, Fabio Panizzuti, Sergio Foresti, Pietro Pioltelli, Giuseppe Mancia
Journal: Journal of Hepatology (2002)
‘Easy to treat’ genotypes were not created equal: Can rapid virological response (RVR) level the playing field?
Authors: Andres Duarte-Rojo, Elizabeth Jenny Heathcote, Jordan Jay Feld
Journal: Journal of Hepatology (2011)

Genotypes 2 and 3 (G2/G3) of hepatitis C virus have been lumped together as 'easy to treat'. As a result, guidelines recommend 24 weeks of peginterferon/ribavirin for both. However, a closer look at trials shows that these genotypes are not the same, with G2 infection proving more responsive to peginterferon. The data supporting this conclusion are presented along with possible explanations for the differences observed. Ultimately, decisions must be made about therapy. Rapid virological response (RVR) may be the best parameter predicting successful antiviral therapy. For patients with G2 infection who achieve an RVR, shortened courses of therapy are effective. In contrast, for G3 patients without an RVR, there may be benefit to extending therapy to 48 weeks; however, this requires confirmation in prospective studies. Using RVR to guide therapy may level the playing field between these 'easy to treat' genotypes.
Newborn Metabolic Screening: Past and Prospect
Authors: Harvey L. Levy
Journal: New England Journal of Medicine (1975)

One of the most exciting and potentially one of the most important new developments in medicine is that of newborn screening for metabolic disorders. This screening was begun on a statewide basis in Massachusetts in 1962 with the use of the Guthrie test for phenylketonuria.1 Since then routine newborn screening for that disorder has become mandatory in 43 states, has spread widely in Europe, and most recently has begun in other areas of the world. A number of these screening programs are now testing for many metabolic disorders in addition to phenylketonuria.2 The most recent important development has been the . . .
Sustained retention of tetradecylthioacetic acid after local delivery reduces angioplasty-induced coronary stenosis in the minipig
Authors: R Pettersen
Journal: Cardiovascular Research (2001)

Objective: The sulfur containing tetradecylthioacetic acid (TTA) has a profound effect on lipid metabolism and may also exert antioxidant and anti-inflammatory actions and thereby counteract coronary stenosis after angioplasty balloon injury. This study examined the possible modulatory effects of TTA, delivered locally, on coronary stenosis in minipigs and the underlying mechanisms of action. Methods: Coronary balloon angioplasty injury using an oversized balloon was performed to 40 coronary arteries (20 minipigs, Sus Scrofa, Gammelsroed) followed by delivery of placebo or TTA via a local drug delivery balloon catheter. TTA was radiolabelled in four pigs. Quantitative coronary angiography and intracoronary ultrasound (ICUS) were performed before and after injury, and after 4 weeks of follow-up. The arteries were examined with histomorphometry. The antioxidant and anti-inflammatory effects of TTA were examined on LDL oxidation and stimulated release of interleukin (IL)-2 and IL-10 in human peripheral blood mononuclear cells (PBMC), respectively. Results: Radioactive TTA was present in the coronary wall after 4 weeks. Angiographic minimal luminal diameter (mean±S.E.M.) in the placebo and TTA group was 1.3±0.1 vs. 2.2±0.2 mm (P<0.01) at follow-up, stenosis rate was 55 and 20% (P<0.01). Remodeling was −0.56±0.12 in the TTA group and −1.28±0.09 in the placebo group (P<0.01). TTA significantly prolonged the lag time of LDL oxidation. In phytohemagglutinin stimulated PBMC, TTA significantly decreased IL-2 levels and increased IL-10 levels suggesting a marked anti-inflammatory net effect. Conclusions: Local delivery of TTA reduces coronary artery stenosis after PTCA as assessed by both angiographic, histomorphometric and ICUS examinations by influencing vessel remodeling rather than intimal hyperplasia. The underlying mechanism(s) seem to involve antioxidant and anti-inflammatory effects of this fatty acid analogue.
Decreased erythropoietin responsiveness to iron deficiency anemia in the elderly
Authors: Joëlle Nafziger, Karine Pailla, Liliane Luciani, Jean‐Paul Andreux, Olivier Saint‐Jean, Nicole Casadevall
Journal: American Journal of Hematology (1993)

The prevalence of anemia in the elderly raises the question of an inappropriate secretion of erythropoietin in response to increased demands. Therefore, the serum erythropoietin concentration of elderly patients (74-95 years) with iron deficiency anemia was measured and compared to that of iron deficiency anemic adults (25-60 years). A lowered erythropoietin secretion in response to anemia was observed in elderly patients in comparison with adults. However, the serum erythropoietin of the anemic elderly was inversely correlated with hemoglobin levels as shown for the anemic adults. The progressive reduction of the renal function observed with aging could explain the decreased capacity of erythropoietin secretion in elderly patients.
Vascular endothelium-leukocyte interaction; sticking shear force in venules.
Authors: G W Schmid-Schoenbein, Y C Fung, B W Zweifach
Journal: Circulation Research (1975)

To determine the shear force acting on a white blood cell sticking to the endothelium of a blood vessel, the flow field about a single white blood cell in a venule was determined by hign-speed motion picture photomicrography. The force acting on the white blood cell was then calculated according to the principles of fluid mechanics. In this paper, the calculation was made using an experimentally determined dimensionless shear force coefficient obtained from a kinematically and dynamically similar model. The large physical model of the hemodynamic system could be easily instrumented, and the shear force acting on the model cell and the flow field around it were measured. The data were then used to calculate a shear force coefficient. On the basis of dynamic similarity, this shear force coefficient was applied to the white blood cell in the venule. The shear force coefficient was strongly influenced by the hematocrit, so in vivo hematocrits were measured from electron micrographs. It was found that in the venules of the rabbit omentum a white blood cell sticking to the endothelial wall was subjected to a shear force in the range of 4 times 10--5 dynes to 234 times 10--5 dynes; the exact value depended on the size and motion of the white blood cell, the size of the blood vessel, the velocity of the blood flow, and the local hematocrit, which varied between 20% and 40% in venules of about 40 mum in diameter. The contact area between the white blood cell and the endothelial cell was estimated, and the shear stress was found to range between 50 dynes/cm-2 and 1060 dynes/cm-2. The normal stress of interaction between the white blood cell and the endothelium had a maximum value that was of the same order of magnitude as the shear stress. The accumulated relative error of the experimental procedure was about 49%. The instantaneous shear force was a random function of time because of random fluctuations of the hematocrit.
Increased thromboxane biosynthesis in a human preparation of platelet activation: biochemical and functional consequences of selective inhibition of thromboxane synthase.
Authors: I A Reilly, J B Doran, B Smith, G A FitzGerald
Journal: Circulation (1986)

Although thromboxane A2 is a potent platelet agonist and vasoconstrictor in vitro, our knowledge of its pathophysiologic importance in human disease is limited. To facilitate the elucidation of its role in vivo, we sought to define a human syndrome in which pharmacologic interventions designed to inhibit the biosynthesis or biologic actions of thromboxane A2 might be appropriately assessed. Patients with severe peripheral vascular disease were selected on the basis of elevated plasma beta-thromboglobulin and circulating platelet aggregates and compared with healthy, age-matched control subjects. In addition to the platelet indexes, their bleeding time was shorter and excretion of 2,3-dinor-thromboxane B2, a noninvasive index of thromboxane formation in vivo, and 2,3-dinor-6-keto-prostaglandin F 1 alpha, the major urinary metabolite of prostacyclin, was markedly increased. A selective inhibitor of thromboxane synthase, imidazo (1,5-2) pyridine-5-hexanoic acid, was administered to these patients under randomized, double-blind, controlled conditions. Platelet aggregation ex vivo, the circulating platelet aggregate ratio, and the bleeding time were all unaltered, despite almost maximal inhibition of platelet thromboxane formation 1 hr after dosing. By contrast, pronounced inhibition of aggregation was observed when platelet cyclooxygenase was inhibited by aspirin. During long-term dosing with the synthetic inhibitor, inhibition of thromboxane biosynthesis was incomplete, which would permit continued thromboxane-dependent platelet aggregation to occur. However, the failure of enzyme blockade to influence platelet function at the time of maximal drug action, despite efficient inhibition of serum thromboxane B2, suggests that accumulation of proaggregatory endoperoxides is also likely to have contributed to the persistence of platelet activation. We have characterized a human preparation in which platelet activation coexists with increased thromboxane biosynthesis. In this setting, platelet activation persists despite long-term administration of a thromboxane synthase inhibitor in a dosing regimen representative of that employed in clinical trials. Prolongation of drug action and combination with antagonists of the shared endoperoxide/thromboxane A2 receptor may be necessary to assess the potential of selective inhibition of thromboxane synthase as a therapeutic strategy in man.
Preoperative staging of lung cancer: accuracy of computed tomography versus mediastinoscopy.
Authors: P Goldstraw, M Kurzer, D Edwards
Journal: Thorax (1983)

Forty-four patients coming to surgery for carcinoma of the bronchus underwent preoperative staging of the mediastinum by computed tomography (CT scanning) and surgical exploration of the mediastinum by cervical mediastinoscopy or left anterior mediastinotomy or both. Where mediastinal nodes were affected the sensitivity and specificity of computed tomography was inferior to that of mediastinoscopy (57% and 85% versus 71% and 100%). The sensitivity of computed tomography in predicting mediastinal invasion was superior to that of mediastinoscopy (77% v 46%), especially in the case of lower-lobe tumours (67% v 17%). Mediastinoscopy had the considerable advantage of 100% specificity. In the assessment of hilar lymphadenopathy computed tomography had a sensitivity of 38% and a specificity of 64%. In cases where computed tomography showed a normal mediastinum or enlargement of the hilar glands only, mediastinal exploration conferred no additional information and could have been omitted. A computed tomography scan showing mediastinal abnormality is an indication for mediastinoscopy and not a contraindication to surgery. In 23 patients computed tomography showed some abnormality of the mediastinum, confirmed at mediastinoscopy in 12 cases. The remaining 11 patients underwent thoracotomy, resection being carried out in nine. Postsurgical staging showed that six of these tumours were N0 lesions without invasion; in two further N0 cases there was a minor degree of mediastinal invasion which did not prevent resection, and the remaining tumour was N1 without invasion.