tbuckley/cabot-search huggingface dataset:
Modulation of delayed afterdepolarisations by 1 adrenergic receptor subtypes
Authors: J. H. Lee, M. R Rosen
Journal: Cardiovascular Research (1993)

Objective: The aim was to evaluate the role of α1 adrenoceptor stimulation and selective receptor subtype blockade on delayed afterdepolarisations induced by high extracellular calcium ([Ca2+]O=8.1 mM) and by ouabain (2 × 10−7 M) in canine Purkinje fibres. Methods: Standard microelectrode techniques were used to record transmembrane action potentials from Purkinje fibres paced at cycle length=500 ms. The drive was interrupted for 5 s every minute to allow observation of delayed afterdepolarisations or any subsequent spontaneous rhythms. Results: The α1 adrenoceptor agonist phenylephrine, 1 × 10−7 M, increased the amplitude of delayed afterdepolarisations induced by high [Ca] from 4.2(SEM 0.4) to 5.4(0.2) mV (p < 0.05), and by ouabain from 4.3(0.6) to 6.9(1.0) mV (p < 0.05). The selective α1 adrenoceptor subtype antagonist WB 4101, 1 × 10−7 M, blocked the effect of phenylephrine on delayed afterdepolarisations induced by ouabain+phenylephrine [DAD=4.6(0.6), p < 0.05] but decreased the amplitude of those induced by Ca+phenylephrine, to 2.0(0.3) mV (p < 0.05). In contrast, the selective α1b adrenoceptor antagonist chloroethylclonidine, 1 × 10−7 M, increased the amplitude of delayed afterdepolarisations induced by Ca and phenylephrine to 6.6(0.6) mV (p < 0.05) and by ouabain and phenylephrine to 12.6(2.0) mV (p < 0.05). Conclusions: α1 Adrenoceptor subtypes modulate the amplitude of delayed afterdepolarisations induced by ouabain and by high [Ca]. The chloroethylclonidine-blocked α1 adrenoceptor subtype decreases, and the WB 4101-blocked subtype potentiates, this arrhythmogenic mechanism. Cardiovascular Research 1993;27:839-844
Free-radical metabolites of acetaminophen and a dimethylated derivative.
Authors: V Fischer, P R West, L S Harman, R P Mason
Journal: Environmental Health Perspectives (1985)

The oxidation of acetaminophen (4'-hydroxyacetanilide) to the corresponding N-acetyl-p-benzoquinone imines by plant and mammalian peroxidases is discussed. The acetaminophen free radical (N-acetyl-4-aminophenoxyl) has been reported as an intermediate. It is very reactive and forms melanin-like polymeric products. Application of a fast-flow system makes it possible to detect the transient species and clearly distinguish it from persistent paramagnetic melanin polymers. A model system, leading to more stable metabolites, can be obtained by introduction of methyl groups next to the oxygen, 3',5'-dimethylacetaminophen (3',5'-dimethyl-4'-hydroxyacetanilide). The ESR spectrum of the free radical formed could be completely analyzed and confirmed by deuterium substitution. The data are consistent with the assignment to a phenoxyl free radical (N-acetyl-2,6-dimethyl-4-amino-phenoxyl). Its formation is discussed in terms of substrate, hydrogen peroxide and enzyme concentration dependence. It is believed to be formed via a direct one-electron oxidation of 3',5'-dimethyl-4'-hydroxy-acetanilide. The radical does not form polymers or react with nucleophiles. Its redox behavior is discussed. The possible reaction of these phenoxyl free radicals with oxygen is thought to be negligible.
Catching up the orthopods.
Authors: G. Evans, J. M. Egan
Journal: BMJ (1988)

could be replicated in Britain for about £50m.'The current British system compensates about three people out of every 100 000 of the population with an award of £15 000, whereas the Swedish system compensates 10 times as many people with much greater efficiency and an average award of about £3200.Now that lawyers and economists are supporting no fault compensation it is surely time for the government to think again-particularly when it ultimately meets most of the costs.
Fatal poisoning with methyl isothiocyanate.
Authors: B K Sharma, S Singh, R Mehta
Journal: BMJ (1981)

valproate was reduced to 200 mg twice daily even after treatment for three months.We suggest that sodium valproate should be considered among the drugs of first choice in the management of hemiballismus caused by a vascular lesion in view of its apparent efficacy in this patient and the low incidence of side effects associated with its use, especially the absence of unwanted sedation.
PDGFRα-expressing mesenchyme regulates thymus growth and the availability of intrathymic niches
Authors: William E. Jenkinson, Simona W. Rossi, Sonia M. Parnell, Eric J. Jenkinson, Graham Anderson
Journal: Blood (2006)

Abstract The thymus provides a specialized site for the production of T cells capable of recognizing foreign antigens in the context of self–major histocompatibility complex (MHC) molecules. During development, the thymus arises from an epithelial rudiment containing bipotent progenitors that differentiate into distinct cortical and medullary epithelial cells to regulate the maturation and selection of self-tolerant CD4+ and CD8+ T cells. In addition to their differentiation, thymic epithelial cells undergo cellular expansion to ensure that sufficient intrathymic cellular niches are available to support the large number of immature thymocytes required to form a self-tolerant T-cell pool. Thus, intrathymic T-cell production is intimately linked to the formation and availability of niches within thymic microenvironments. Here, we show the increase in intrathymic niches caused by the proliferation of the epithelium in the developing thymus is temporally regulated, and correlates with the presence of a population of fetal thymic mesenchyme defined by platelet-derived growth factor receptor α (PDGFRα) expression. Depletion of PDGFRα+ mesenchyme from embryonic thymi prior to their transplantation to ectopic sites results in the formation of functional yet hypoplastic thymic tissue. In summary, we highlight a specialized role for PDGFRα+ fetal mesenchyme in the thymus by determining availability of thymic niches through the regulation of thymic epithelial proliferation.
The Air-conditioning Mechanism of the Nose
Authors: V. Negus
Journal: BMJ (1956)

when the simulation or self-injury is frankly acknowledged and discussed, will do well and become useful and effective rather than neurotic and dependent members of society.A few, seem prepared to take matters to extremes, and one of us has experienced elsewhere a case of this type, not included in our series, which terminated fatally.However.we feel in no doubt that the great majority of these patients fully justify every effort made on their behalf despite the deliberately produced natule of their lesions. SummaryReference is made to 19 patients referred from other departments of the United Birmingham Hospitals for psychiatric assessment on account of deliberate illness or injury.Relevant factors in these cases are tabulated, and five, including two of anorexia nervosa, are described at greater length.Consideration is given to the nosological status of such patients, with particular reference to the diagnosisof anorexia nervosa and of hysteria.The diagnosis and prognosis are described and sugges- tions made for treatment.We are indebted to our medical and surgical colleagues for referring these cases and for their patient help, and also to the nursing staff and psychiatric social workers for their invaluable contributions.We also wish to thank Mr. T. F.
Compulsory preschool jabs would fan the antivaccination lobby's fire
Authors: D. Spence
Journal: BMJ (2013)

Even in the half light I could see the widespread meningococcal rash. He was semiconscious. My hands trembled as I drew up the penicillin. We are all captives to our experience, irrespective of the evidence. So when asked how I can be sceptical about statins but not vaccinations I am incredulous. Clearly, vaccinations work: there is a biological model with measurable effect, and the consequences of infectious disease are terrible. The huge decline in infections after vaccination, and the eradication of others, seems irrefutable proof.1 2 3 But evidently not everyone thinks like that.⇑

There is an …
Hepatic p38α regulates gluconeogenesis by suppressing AMPK
Authors: Yanyan Jing, Wei Liu, Hongchao Cao, Duo Zhang, Xuan Yao, Shengjie Zhang, Hongfeng Xia, Dan Li, Yu-cheng Wang, Jun Yan, Lijian Hui, Hao Ying
Journal: Journal of Hepatology (2015)
Biological clustering supports both “Dutch” and “British” hypotheses of asthma and chronic obstructive pulmonary disease
Authors: Michael A. Ghebre, Mona Bafadhel, Dhananjay Desai, Suzanne E. Cohen, Paul Newbold, Laura Rapley, Jo Woods, Paul Rugman, Ian D. Pavord, Chris Newby, Paul R. Burton, Richard D. May, Chris E. Brightling
Journal: Journal of Allergy and Clinical Immunology (2014)

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases.We sought to determine, in terms of their sputum cellular and mediator profiles, the extent to which they represent distinct or overlapping conditions supporting either the "British" or "Dutch" hypotheses of airway disease pathogenesis.We compared the clinical and physiological characteristics and sputum mediators between 86 subjects with severe asthma and 75 with moderate-to-severe COPD. Biological subgroups were determined using factor and cluster analyses on 18 sputum cytokines. The subgroups were validated on independent severe asthma (n = 166) and COPD (n = 58) cohorts. Two techniques were used to assign the validation subjects to subgroups: linear discriminant analysis, or the best identified discriminator (single cytokine) in combination with subject disease status (asthma or COPD).Discriminant analysis distinguished severe asthma from COPD completely using a combination of clinical and biological variables. Factor and cluster analyses of the sputum cytokine profiles revealed 3 biological clusters: cluster 1: asthma predominant, eosinophilic, high TH2 cytokines; cluster 2: asthma and COPD overlap, neutrophilic; cluster 3: COPD predominant, mixed eosinophilic and neutrophilic. Validation subjects were classified into 3 subgroups using discriminant analysis, or disease status with a binary assessment of sputum IL-1β expression. Sputum cellular and cytokine profiles of the validation subgroups were similar to the subgroups from the test study.Sputum cytokine profiling can determine distinct and overlapping groups of subjects with asthma and COPD, supporting both the British and Dutch hypotheses. These findings may contribute to improved patient classification to enable stratified medicine.
PRIMARY CARCINOMA OF THE NASAL CHAMBERS.
Authors: WM. EDGAR DARNALL
Journal: JAMA (1903)

It is not common to find malignant disease attacking the nasal chamber. When it does, however, it is found to be sarcoma more frequently that carcinoma. Kyle and Bosworth both point out the infrequency of these conditions in the nose. The latter, in 1889, succeeded in collecting 41 cases of sarcoma and 30 cases of carcinoma of the nasal cavities. Gibb,<sup>1</sup>after a careful search of the literature, has been able to add 70 cases of sarcoma and 48 of carcinoma, making a total of 111 cases of sarcoma and 78 cases of carcinoma. In a special practice of ten years he has only seen one case of primary carcinoma of the nasal chambers, but he considers sarcoma not nearly so rare as statistics would seem to indicate. The case of carcinoma I wish to add to this list occurred in a German woman of 69 years of
Airway Bypass Stents for Emphysema, Algorithm to Exclude Precapillary Pulmonary Hypertension, and Sildenafil for Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction
Authors: Matthew R. Lammi, Nicholas Panetta, Maria Elena Vega
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

In selected patients with emphysema, lung volume reduction surgery has been shown to improve exercise capacity, quality of life, and survival (2). Because of restrictive inclusion criteria and risk of surgery, there has been interest in bronchoscopic lung volume reduction as an alternative to lung volume reduction surgery. Creating airway bypass tracts (ABTs) attempts to bypass collapsed small airways, allowing air to escape on expiration. The Exhale Airway Stents for Emphysema (EASE) trial was the first randomized, double-blind, sham-controlled study of ABTs (1). Patients were included if they had homogeneous emphysema with an FEV1 less than 50% predicted and an RV/TLC greater than 0.65. Of the 1,522 patients assessed for eligibility, 208 were randomized to ABT and 107 to sham bronchoscopy. All patients had bronchoscopy under general anesthesia; the intervention group had passages created in the airway and paclitaxel stents placed to maintain patency. Bayesian analysis did not show any superiority of ABT for the coprimary efficacy end point, which was met if the FVC increased by at least 12% and modified Medical Research Council (mMRC) score fell by 1 point from baseline at 6 months of follow-up. Mean FVC increased on Day 1 in the ABT group, but this returned to baseline by 3 months. Mean mMRC scores were significantly lower only at the 6-month time point in the intervention group. This trial used a robust randomized, sham-controlled study design that included patients most likely to benefit from the treatment. There was no benefit in the coprimary end point, likely due to stent expectoration and low rates of stent patency (66% onDay 1 and 21% at 6mo). Although there were no differences in composite safety end points or 6-month mortality between the groups, the risk of chronic obstructive pulmonary disease exacerbation or infection was almost twofold higher in the treatment group. This highlights the importance of noting individual safety end points that may be masked by reporting a composite end point alone. The EASE trial demonstrates that airway bypass tract formation with paclitaxel stents does not improve outcomes in patients with severe homogeneous emphysema. This is an interesting example of how theoretical benefit was attained through an intervention but was not sustained because of technical aspects of the procedure.
Activity of Gefitinib in a Non–Small-Cell Lung Cancer Patient with Both Activating and Resistance EGFR Mutations
Authors: Alessandro Morabito, Raffaele Costanzo, Anna Maria Rachiglio, Raffaella Pasquale, Claudia Sandomenico, Renato Franco, Agnese Montanino, Elisabetta De Lutio, Gaetano Rocco, Nicola Normanno
Journal: Journal of Thoracic Oncology (2013)
Atrophic gastric changes in both Helicobacter felis and Helicobacter pylori infected mice are host dependent and separate from antral gastritis.
Authors: T Sakagami, M Dixon, J O'Rourke, R Howlett, F Alderuccio, J Vella, T Shimoyama, A Lee
Journal: Gut (1996)

BACKGROUND/AIMS: The role of host factors has been neglected in studies of the pathogenesis of Helicobacter associated disease. The aim of this study was to assess the response of different mouse strains to infection with a single strain of Helicobacter felis. METHOD: Six strains of inbred mice were infected with the identical H felis culture and were killed at one month, two months, and six months after infection to assess histopathological changes. In addition, two strains of mice were infected with a mouse adapted strain of H pylori and examined at six months after infection. RESULTS: In SJL, C3H/He, DBA/2, and C57BL/6 infected mice, severe to moderate chronic active gastritis was observed only in the body of the stomach, which increased in severity over time with specialised cells in the body glands being replaced. As the severity of this damage in the body increased and atrophic changes were seen, the level of bacterial colonisation of the antrum decreased. In contrast, in BALB/c and CBA mice, there was only mild gastritis in the antrum, no remarkable changes were detected in their body mucosa, and no atrophy was seen over time. In both these strains of mice, heavy bacterial colonisation was seen, which tended to increase over the period of the experiment. Of particular importance in this experiment was that bacterial colonisation was mainly restricted to the antrum yet the atrophy, when present, was only observed in the body of the stomach. H pylori infected C3H/He mice showed moderate colonisation of the antrum, which persisted up to six months with little development of atrophy. In contrast, H pylori in C57BL/6 mice showed excellent colonisation of the antrum at two months but six months after infection there was moderate to severe body atrophy, which was associated with a loss of bacteria from the antrum. CONCLUSIONS: These findings challenge current concepts of the development of Helicobacter induced atrophy in that active chronic gastritis of antrum or the body mucosa, or both, is not a prerequisite. They also suggest an autoimmune basis for the pathology although no autoantibody or antibody to the H+/K+ ATPase was detected. Loss of infecting helicobacters from the stomach together with development of an atrophic gastritis in the body of the stomach is similar to the pattern found in certain H pylori infected human subjects.
Secretory immunoglobulin A in pancreatic juice and pancreatic tissue of patients with chronic pancreatitis
Authors: J Emmrich, M Seyfarth, P Conradi, F Plath, G Sparmann, M Löhr, S Liebe
Journal: Gut (1998)

The predominance of secretory IgA (S-IgA) in intestinal secretions compared with blood is well established, but concentrations of this protein in pancreatic juice and its origin, especially in chronic pancreatitis, are unknown.To investigate the role of S-IgA in chronic pancreatitis.Twenty one patients with chronic pancreatitis (group I), three patients with proven malignancies (group II), and 12 patients without pancreatic disease (group III).Pure human pancreatic juice was collected endoscopically in four fractions after consecutive stimulation with secretin and cholecystokinin (CCK). Samples were analysed for S-IgA, protein, trypsinogen, and proteolytic activity.The S-IgA level was significant increased in fraction 1 of pancreatic juice of group I (1210 (1411) ng/ml) compared with controls (33 (70) ng/ml). Protein concentrations and trypsinogen content were lower in group I than in the other groups. Proteolytic activity could be observed in 53% of all 133 pancreatic juice samples, but in 87% of fraction 1. In pancreatic tissue of three patients with chronic pancreatitis both IgA and secretory component were detected by immunohistology. Expression of the secretory component by human pancreatic epithelial cells was increased in patients with chronic pancreatitis compared with normal controls. The concentration of S-IgA in pancreatic juice did not correlate with the serum S-IgA level. In contrast, serum levels of S-IgA were decreased in patients with chronic pancreatitis.There are high levels of S-IgA in human pancreatic juice following chronic inflammation and a protective role is suggested for this immunoglobulin.
Vitamin A in the treatment of lichen planus pigmentosus
Authors: L.K. Bhutani, Mary George, S.M. Bhate
Journal: British Journal of Dermatology (1979)

Journal Article Vitamin A in the treatment of lichen planus pigmentosus Get access L.K. Bhutani, L.K. Bhutani Department of Dermato‐Venereology, All India Institute of Medical Sciences, New Delhi‐10016, India Search for other works by this author on: Oxford Academic Google Scholar Mary George, Mary George Department of Dermato‐Venereology, All India Institute of Medical Sciences, New Delhi‐10016, India Search for other works by this author on: Oxford Academic Google Scholar S.M. Bhate S.M. Bhate Department of Dermato‐Venereology, All India Institute of Medical Sciences, New Delhi‐10016, India Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 100, Issue 4, 1 April 1979, Pages 473–475, https://doi.org/10.1111/j.1365-2133.1979.tb01653.x Published: 01 April 1979
Angiocardiography of multiple ventricular septal defects in infancy.
Authors: K E Fellows, G R Westerman, J F Keane
Journal: Circulation (1982)

Biplane cineventriculography in 364 infants 1 year of age or younger demonstrated multiple ventricular septal defects (VSDs) in 56 (15%).Among 111 infants with VSDs (with or without patent ductus arteriosus), 18 (16%) had multiple VSDs, whereas 14 of 39 infants (36%) with VSD and coarctation of the aorta had multiple VSDs.The incidence of multiple VSDs in infants with tetralogy of Fallot was 7% (eight of 117), in infants with d-transposition of the great arteries 19% (eight of 43), and in infants with common atrioventricular canal 15% (eight of 54).Perioperative axially angled cineangiocardiography correctly predicted the presence of multiple VSDs in 13 of 15 infants (86%) who underwent operation.THE MORTALITY RATE for surgery of congenital heart disease when associated with multiple ventricular septal defects (MVSDs) is 14-17%,' 2 compared with 4% when a single VSD is present.3With the trend in many medical centers toward surgical correction of congenital heart defects during infancy," 4,5 precise preoperative diagnosis in babies is becoming increas- ingly important.Our previous experience, in which the presence of MVSDs was identified preoperatively in only 55% of patients operated upon,' indicates that preoperative diagnosis must be improved.This study was undertaken to determine the inci- dence of MVSDs in infants with ventricular septal defect (VSD), VSD and coarctation (VSD/CoAo), tetralogy of Fallot (T/F), d-transposition (d-TGA) and common atrioventricular canal (CAVC) using cineangiocardiography.A second objective was to evaluate whether the use of axially angled views im- proved preoperative diagnosis.Additionally, the inci- dence of spontaneous closure of one or more of these defects was examined among those with VSD and VSD/CoAo by clinical observation and subsequent cardiac catheterization, and among those with d-TGA by repeat cineangiography.
Blood Pressure Effects of Acute Hypercalcemia
Authors: PETER WEIDMANN
Journal: Annals of Internal Medicine (1972)

The effect of acute hypercalcemia on blood pressure was evaluated in 57 persons (7 with normal serum creatinine and 50 with mild to severe renal failure) while they received an infusion of calcium. As serum calcium rose, hypertension either developed or was aggravated in one of the normal subjects and in 41 of the patients with renal failure; the change in blood pressure was not related to the presence of preexisting hypertension. A significant correlation between the changes in both systolic and diastolic blood pressure and the increment in plasma calcium was found. Moreover, the hypertensive response to elevation in serum calcium was more common in patients with advanced renal failure (serum creatinine more than 4 mg/100 ml). The observations show that acute hypercalcemia can cause an elevation in blood pressure, and renal failure may predispose to such a hypertensive response.