tbuckley/cabot-search huggingface dataset:
Human serum IgE‐mediated mast cell degranulation shows poor correlation to allergen‐specific IgE content
Authors: F. Marchand, S. Mecheri, L. Guilloux, B. Iannascoli, A. Weyer, U. Blank
Journal: Allergy (2003)

Background: Although allergen‐specific IgE content in serum can be determined immunochemically, little is known about the relationship between this parameter and the strength of the degranulation response upon allergen triggering. Objectives: Analyse the degranulation capacity of immunochemically defined purified and serum IgE after challenge with anti‐IgE or allergen using a rat mast cell line (RBL) transfected with the α ‐chain of the human high‐affinity IgE receptor (Fc ɛ RI). Methods: Purified IgE specific for 4‐hydroxy‐3nitrophenylacetyl, purified IgE of unknown specificity, and sera from allergic patients sensitive to Dermatophagoides pteronyssinus and Dactylis glomerata were assessed. Degranulation was measured by a β ‐hexosaminidase release assay after anti‐IgE or allergen‐specific challenge. Results: For purified monoclonal IgE a significant correlation ( r = 0.97) was found between the proportion of bound allergen‐specific IgE and the strength of the degranulation response. In contrast, no correlation ( r = 0.27) was detected after sensitization with serum IgE. Conclusion: Our studies demonstrate that mast cell activation mediated through IgE from allergic patients is a result of complex relationships that are not only dependent on allergen‐specific IgE content but also relate to the capacity to efficiently sensitize and trigger the signalling responses that lead to degranulation.
Mothers' experiences of induction
Authors: A. Cartwright
Journal: BMJ (1977)

Mothers of a random sample of 2182 legitimate live births were interviewed about their experiences of pregnancy, labour, and delivery. Of these, 24% reported that their labours were induced, and data about this from a subsample of mothers tallied with information obtained through the doctors in charge in 88% of cases. All but 3% of the mothers who were induced perceived some medical reason for the induction. The proportion of inductions in the 24 study areas ranged from 6% to 39%. A relatively small proportion of labours in "teaching" hospitals, small hospitals with less than 100 beds, and GP maternity hospitals were induced, but a comparatively high proportion of private patients had an induction. There was no clear association between induction and the mother's age or parity. Despite being given more pain relief, those who were induced reported similar intensities of pain during the first and second stages of labour to those whose labour started spontaneously; they also reported that they had "bad pains" for a similar period. The period they had contractions was shorter for the induced than for those starting spontaneously, and the intensity of pain at delivery was rated somewhat less by those who were induced.There was no difference between induced babies and others in the proportion who were held by their mothers immediately after their birth. Two-fifths of the mothers who were induced would have liked more information about induction; and a similar proportion said they had not discussed induction with a doctor, midwife, or nurse during their pregnancy. Only 17% of the mothers who had an induction said they would prefer to be induced if they had another baby. This contrasts with 63% of those who had epidural analgesia who would opt for the same procedure next time, while 83% of those who had had a baby in hospital, and 91% of those having had a home birth, would want their next baby in the same type of place.
Bile acid profiles in peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency.
Authors: P T Clayton, E Patel, A M Lawson, R A Carruthers, J Collins
Journal: Journal of Clinical Investigation (1990)

Fast atom bombardment mass spectrometry and gas chromatography-mass spectrometry were used to analyze bile acids in the body fluids of an infant (L.C.) whose liver contained no immunoreactive peroxisomal 3-oxoacyl-CoA thiolase. The profiles were compared with those of six patients with undetectable peroxisomes (Zellweger syndrome) and two siblings (N.B. and I.B.) whose defect of peroxisomal beta-oxidation could not be localized by morphological studies of peroxisomes or by immunoblotting of peroxisomal beta-oxidation proteins. 3 alpha, 7 alpha, 12 alpha-Trihydroxy-5 beta-cholestan-26-oic acid (THCA) was present in bile and plasma of all patients. However, bile from L.C., N.B. and I.B. contained unconjugated varanic acid (3 alpha, 7 alpha, 12 alpha, 24-tetrahydroxy-5 beta-cholestan-26-oic acid) as the major C27 bile acid, whereas bile from Zellweger patients contained only small amounts of varanic acid. In the bile from L.C. two isomers of varanic acid were present; in the bile from N.B. and I.B. a single isomer predominated. L.C., N.B., and I.B. all produced bile containing small amounts of (24E)-3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-en-26-oic acid [( 24E]-delta 24-THCA), its [24Z]- isomer, 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-23-en-26-oic acid and 3 alpha, 7 alpha, 12 alpha-trihydroxy-27-nor-5 beta-cholestan-24-one. The results provide evidence for peroxisomal pathways for cholic acid synthesis in man via THCA, delta 24-THCA and varanic acid and show that bile acid analyses can be used to diagnose peroxisomal thiolase deficiency.
Vascular Dysfunction in Patients with Chronic Arsenosis Can Be Reversed by Reduction of Arsenic Exposure
Authors: Jingbo Pi, Hiroshi Yamauchi, Guifan Sun, Takahiko Yoshida, Hiroyuki Aikawa, Wataru Fujimoto, Hiroyasu Iso, Renzhe Cui, Michael P. Waalkes, Yoshito Kumagai
Journal: Environmental Health Perspectives (2004)

Chronic arsenic exposure causes vascular diseases associated with systematic dysfunction of endogenous nitric oxide. Replacement of heavily arsenic-contaminated drinking water with low-arsenic water is a potential intervention strategy for arsenosis, although the reversibility of arsenic intoxication has not established. In the present study, we examined urinary excretion of cyclic guanosine 3 ,5 -monophosphate (cGMP), a second messenger of the vasoactive effects of nitric oxide, and signs and symptoms for peripheral vascular function in 54 arsenosis patients before and after they were supplied with low-arsenic drinking water in an endemic area of chronic arsenic poisoning in Inner Mongolia, China. The arsenosis patients showed a marked decrease in urinary excretion of cGMP (mean +/- SEM: male, 37.0 +/- 6.1; female, 37.2 +/- 5.4 nmol/mmol creatinine), and a 13-month period of consuming low-arsenic drinking water reversed this trend (male, 68.0 +/- 5.6; female, 70.6 +/- 3.0 nmol/mmol creatinine) and improved peripheral vascular response to cold stress. Our intervention study indicates that peripheral vascular disease in arsenosis patients can be reversed by exposure cessation and has important implications for the public health approach to arsenic exposure.
P113 The Use Of Local Anaesthesia In Improving The Patient Experience Of Arterial Blood Gases: Students And Trainers Are Still Not Getting The Message
Authors: Z. Mangera, C. Gunasekera, J. Kinley, J. King, B. Walker, O. Cohen, P. Dilworth
Journal: Thorax (2014)

<h3>Background</h3> BTS guidelines (2008) states that “local anaesthesia (LA) should be used for all arterial blood gas (ABG) specimens except in emergencies<sup>1</sup> as it improves the patient experience. A survey conducted in 2012 revealed only 5% of junior doctors regularly use LA with ABGs.<sup>2</sup> We were interested to determine if this has improved and establish whether medical students are being orientated to this practice. <h3>Methodology</h3> This is a multicentre prospective study. A questionnaire survey was distributed to 4th year medical students and junior doctors affiliated with UCL Medical School. Questions related to their actual experiences of using LA with ABGs and barriers to using LA. <h3>Results</h3> 94 medical students completed the questionnaire. Students used LA 17% of the time out of 54 supervised procedures. 29% were actively discouraged from using LA by their supervising doctor. 10% felt the general culture amongst supervising doctors was resistant to using LA. Amongst the 86 surveyed doctors, 91% never or rarely (&lt;10% of the time) used LA, 5% sometimes (&lt;25% of the time) and 3% used it regularly (&gt;75% of the time). 65% of doctors were not aware that LA was advised in national guidance. 40% of respondents felt it would not reduce the pain of the procedure and 38% did not know the technique involved of using LA. <h3>Conclusion</h3> The use of LA is extremely poor as has been found previously.<sup>1</sup> The reasons reflect a lack of awareness and a culture that is experienced from the moment the enter the clinical environment as medical students. In order to improve the patient experience we have introduced an intervention at the level of the medical school and junior doctor teaching which includes mandatory training and encouraging affiliated trusts to help create a culture where giving LA is the norm. We will fully report on the results and success of our interventions. <h3>References</h3> O’Driscoll, Howard LS, Davison AG. BTS guideline for emergency oxygen use in adult patients. <i>Thorax</i>. 2008; 63 (Suppl VI):vi1–vi73 Khan F <i>et al</i>. The Use of Local Anaesthesia For Arterial Blood Gas Sampling – A Multicentre Survey. <i>Thorax</i> 2012;67:A167-A168
Through-the-Scope Balloon Dilatation of Benign Pyloric Stenoses
Authors: W. Schmüdderich, M. Harloff, J. F. Riemann
Journal: Endoscopy (1989)

In 9 patients with benign pyloric stenosis, the stenosis was dilated using through-the-scope (TTS) balloon catheters (diameter 1.5 to 1.8 cm), which can be passed through the biopsy channel of a standard fiberscope under direct vision. In all cases, the stenosis was secondary to fibrous changes in peptic ulcer disease. In addition, all patients had active ulcers. All dilatation treatments were primarily successful: the stenoses were opened for the passage of the fiberscope. There were no complications; even with active ulcers there were no side effects. The treatment was followed by immediate symptomatic relief. On prospective evaluation over a period of 7 months (mean), 6 patients remained asymptomatic, 2 patients had to be dilated again for restenosis and have since been asymptomatic for 1 and 12 months, respectively. One patient had to undergo surgery after 7 months for ulcer perforation into the common bile duct. The TTS technique has considerable advantages over the methods requiring a guide wire. This technique with its easy practicability and low incidence of complications may become a valid alternative to surgical procedures if the good initial results can be confirmed in further studies.
Abstract 2694: DNA copy number aberrant profiles predict complete pathologic tumor response to preoperative chemoradiation therapy in locally advanced rectal cancer
Authors: Zhenbin Chen, Zheng liu, Xiwei Wu, Wenyan Li, Julio Garcia-Aguilar
Journal: Cancer Research (2010)

Abstract Purpose: The treatment of locally advanced rectal cancer includes chemoradiation (CRT) followed by surgical resection. The response of rectal cancers to the CRT is variable. The finding that up to 25% of tumor seem to be totally eradicated by the CRT has raised the question as to whether surgery can be avoided in these patients. Findings predictors or response or resistance to CRT could potentially change the treatment paradigm of rectal cancer patients. In this study we explored DNA copy number alterations as predictors of rectal cancer response to preoperative CRT. Patients and Methods: High-density oligonucleotide-based comparative genomic hybridization (human 244k aCGH kit, Agilent Cor.) was employed to identify the DNA copy number alterations in 89 pretreatment tumor biopsy specimens and paired normal surgical specimens collected from stage II and III rectal cancer patients treated in a prospective multi-institutional study. Data analysis was performed using Nexus Copy Number and Ingenuity Pathway Analysis. A pathologic complete response (pCR), defined as absence of cancer cells in the surgical specimen, was used as clinical end-point. Results: A total of 25 (28%) patients had a pCR. The pCR rate was higher among tumors with low fractional genomic alterations (FGA, ≤21%) (12/26 or 46.1%) compared to tumors with high FGA (&amp;gt;21%) (13/63 or 20.6%) (p&amp;lt;0.02). Gain or losses of individual chromosome segments containing individual candidate genes and miRNAs in tumors with or without pCR are presented in table 1.Chrom. LocationCandidate GeneChangepCRNon- pCRp-valuechr18q21.2SMAD4loss52%82.8%0.0059chr.8p12EIF4EBP1loss8%35.9%0.0085chr.17q12ERBB2gain4%29.7%0.0098chr.16p12.1PRKCBgain4%29.7%0.0098chr.7p15.2hsa-mir-148again32%58.7%0.0352 Conclusion: This study shows that DNA copy number aberrations, measured as a FGA and individual chromosome regions gain and loses, may be predictors of rectal cancer resistance to CRT. This information could be used to select patients that may not benefit from a non-surgical treatment. 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 2694.
Dicing with Death: Chance, Risk and Health
Authors: Deborah Ashby
Journal: BMJ (2004)

Are there any BMJ readers who have not encountered statistics and statisticians at some point in their career? Most medical students, and many other health professionals, have learnt some statistics as undergraduates, and maybe more as part of their postgraduate training. If you have obtained a grant or published a paper, the chances are that some statistician will have acted as statistical consultant or referee, if not as collaborator and coauthor. If you prescribe drugs, you are relying on the many statisticians employed within the pharmaceutical industry, and those involved in the regulation of drugs. …
Case of Diarrhoea and Goitre
Authors: I. Kennedy
Journal: BMJ (1967)

Previously an uninterrupted recovery could confidently have been expected in this type of poisoning once the patient had regained consciousness.This case would suggest that relapse and sudden death may occur in poisoning by tricyclic antidepressant compounds after apparent recovery.The forced diuresis may have kept the patient alive initially and there could be an argument for continuing this treatment in order to wash out the possible second wave of metabolites, which would otherwise contribute to an unexpected relapse.
Factors associated with pruritic papular eruption of human immunodeficiency virus infection in the antiretroviral therapy era
Authors: S.L. Chua, E.H. Amerson, K.S. Leslie, T.H. McCalmont, P.E. Leboit, J.N. Martin, D. Bangsberg, T.A. Maurer
Journal: British Journal of Dermatology (2013)

Pruritic papular eruption (PPE) of HIV is common in HIV‐infected populations living in the tropics. Its aetiology has been attributed to insect bite reactions and it is reported to improve with antiretroviral therapy (ART). Its presence after at least 6 months of ART has been proposed as one of several markers of treatment failure. To determine factors associated with PPE in HIV‐infected persons receiving ART. A case–control study nested within a 500‐person cohort from a teaching hospital in Mbarara, Uganda. Forty‐five cases and 90 controls were enrolled. Cases had received ART for ≥ 15 months and had an itchy papular rash for at least 1 month with microscopic correlation by skin biopsy. Each case was individually matched with two controls for age, sex and ART duration. Twenty‐five of 45 cases (56%) had microscopic findings consistent with PPE. At skin examination and biopsy (study enrolment), a similar proportion of PPE cases and matched controls had plasma HIV RNA < 400 copies mL−1 (96% vs. 85%, P =0·31). The odds of having PPE increased fourfold with every log increase in viral load at ART initiation (P =0·02) but not at study enrolment. CD4 counts at ART initiation and study enrolment, and CD4 gains and CD8+ T‐cell activation measured 6 and 12 months after ART commencement were not associated with PPE. Study participants who reported daily insect bites had greater odds of being cases [odds ratio (OR) 8·3, P <0·001] or PPE cases (OR 8·6, P =0·01). Pruritic papular eruption in HIV‐infected persons receiving ART for ≥ 15 months was associated with greater HIV viraemia at ART commencement, independent of CD4 count. Skin biopsies are important to distinguish between PPE and other itchy papular eruptions.
Hypothalamic Fatty Acid Metabolism Mediates the Orexigenic Action of Ghrelin
Authors: Miguel López, Ricardo Lage, Asish K. Saha, Diego Pérez-Tilve, María J. Vázquez, Luis Varela, Susana Sangiao-Alvarellos, Sulay Tovar, Kawtar Raghay, Sergio Rodríguez-Cuenca, Rosangela M. Deoliveira, Tamara Castañeda, Rakesh Datta, Jesse Z. Dong, Michael Culler, Mark W. Sleeman, Clara V. Álvarez, Rosalía Gallego, Christopher J. Lelliott, David Carling, Matthias H. Tschöp, Carlos Diéguez, Antonio Vidal-Puig
Journal: Cell Metabolism (2008)
A Consortium for Purchase of Blood Products Directed by Physicians
Authors: LOUIS M. ALEDORT
Journal: Annals of Internal Medicine (1988)

Clotting-factor therapy is a costly part of comprehensive hemophilia treatment. Physicians treating patients with hemophilia in New York formed a consortium for the purchasing and regional distribution of clotting-factor concentrates. Concentrates are centrally purchased based on a bidding formula aimed at obtaining the lowest price for quality product while guaranteeing all suppliers continued involvement in a large market area. The consortium has successfully maintained, and, in instances, lowered prices each year. Estimated regional savings this year are more than $750 000 for an anticipated purchase of approximately 60 000 000 units of clotting-factors VIII and IX. Central distribution has additionally lowered costs to participating hospitals. The consortium is able to provide patients and third-party payers with some of the lowest prices for clotting-factor concentrates in the United States. A physician-directed regional approach to purchasing costly medical products might be applied to other areas of clinical medicine.
Bisphenol A Diglycidyl Ether Induces Adipogenic Differentiation of Multipotent Stromal Stem Cells through a Peroxisome Proliferator–Activated Receptor Gamma-Independent Mechanism
Authors: Raquel Chamorro-García, Séverine Kirchner, Xia Li, Amanda Janesick, Stephanie C. Casey, Connie Chow, Bruce Blumberg
Journal: Environmental Health Perspectives (2012)

Background: Bisphenol A (BPA) and bisphenol A diglycidyl ether (BADGE), used in manufacturing coatings and resins, leach from packaging materials into food. Numerous studies suggested that BPA and BADGE may have adverse effects on human health, including the possibility that exposure to such chemicals can be superimposed on traditional risk factors to initiate or exacerbate the development of obesity. BPA is a suspected obesogen, whereas BADGE, described as a peroxisome proliferator–activated receptor gamma (PPARγ) antagonist, could reduce weight gain.Objectives: We sought to test the adipogenic effects of BADGE in a biologically relevant cell culture model.Methods: We used multipotent mesenchymal stromal stem cells (MSCs) to study the adipogenic capacity of BADGE and BPA and evaluated their effects on adipogenesis, osteogenesis, gene expression, and nuclear receptor activation.Discussion: BADGE induced adipogenesis in human and mouse MSCs, as well as in mouse 3T3-L1 preadipocytes. In contrast, BPA failed to promote adipogenesis in MSCs, but induced adipogenesis in 3T3-L1 cells. BADGE exposure elicited an adipogenic gene expression profile, and its ability to induce adipogenesis and the expression of adipogenic genes was not blocked by known PPARγ antagonists. Neither BADGE nor BPA activated or antagonized retinoid "X" receptor (RXR) or PPARγ in transient transfection assays.Conclusions: BADGE can induce adipogenic differentiation in both MSCs and in preadipocytes at low nanomolar concentrations comparable to those that have been observed in limited human biomonitoring. BADGE probably acts through a mechanism that is downstream of, or parallel to, PPARγ.
Timeo Danaos et Globos Ferentes
Authors: Sotiris G. Faltsis
Journal: JAMA (1972)

To the Editor.—  Back in 1957, 1 based on an old Greek saying that old people die either because they fall or because they strain, I tried to find out what straining does to the cardiovascular system.  Thirty-five patients (23 of them more than 40 years of age) with a normal (22 patients) or abnormal (13 patients) cardiovascular system were studied for electrocardiographic and blood pressure changes after defecation was simulated. A balloon was inserted in the sigmoid and was inflated to the point it induced the act of defecation. The results showed an increase of the blood pressure, both maximum and minimum, in all patients, and the development of electrocardiographic abnormalities in 12 of the patients. The changes concerned the QRS complex, the T-wave, and the ST segment. It seems that, as the Greek saying asserts, the irritation of the bowel, even for a normal act, is not devoid
Wanted: Old Instruments for Extracting Teeth
Authors: F. Colyer
Journal: BMJ (1937)

Musculoskeletal pain affects nearly half of all adults, most of whom are vitamin D deficient. Previous findings demonstrated that putative nociceptors (“pain-sensing” nerves) express vitamin D receptors (VDRs), suggesting responsiveness to 1,25-dihydroxyvitamin D. In the present study, rats receiving vitamin D-deficient diets for 2–4 weeks showed mechanical deep muscle hypersensitivity, but not cutaneous hypersensitivity. Muscle hypersensitivity was accompanied by balance deficits and occurred before onset of overt muscle or bone pathology. Hypersensitivity was not due to hypocalcemia and was actually accelerated by increased dietary calcium. Morphometry of skeletal muscle innervation showed increased numbers of presumptive nociceptor axons (peripherin-positive axons containing calcitonin gene-related peptide), without changes in sympathetic or skeletal muscle motor innervation. Similarly, there was no change in epidermal innervation. In culture, sensory neurons displayed enriched VDR expression in growth cones, and sprouting was regulated by VDR-mediated rapid response signaling pathways, while sympathetic outgrowth was not affected by different concentrations of 1,25-dihydroxyvitamin D. These findings indicate that vitamin D deficiency can lead to selective alterations in target innervation, resulting in presumptive nociceptor hyperinnervation of skeletal muscle, which in turn is likely to contribute to muscular hypersensitivity and pain.