tbuckley/cabot-search huggingface dataset:
A monoclonal antibody against the platelet glycoprotein IIb/IIIa receptor complex prevents platelet aggregation and thrombosis in a canine model of coronary angioplasty.
Authors: E R Bates, M J McGillem, J K Mickelson, B Pitt, G B Mancini
Journal: Circulation (1991)

BACKGROUND The comparative effects of aspirin and F(ab')2 fragments of monoclonal antibody 7E3 against the platelet glycoprotein IIb/IIIa receptor on ex vivo platelet aggregation and in vivo thrombosis were studied in a canine coronary balloon angioplasty model. METHODS AND RESULTS Three groups were studied. Group 1 (n = 8) was pretreated with saline placebo, group 2 (n = 8) was pretreated with 325 mg aspirin, and group 3 (n = 8) was pretreated with 0.8 mg/kg 7E3 F(ab')2. Coronary angioplasty was performed in the left anterior descending coronary artery of open-chest dogs under fluoroscopic control; serial measurements of basal and hyperemic coronary blood flows were then made for 2 hours after application of an external stenosis that decreased hyperemic flow by 50%. There were no significant differences in platelet counts or hemodynamic measurements during the experiments. Platelet aggregation was decreased by treatment: group 1, 64 +/- 13% versus 50 +/- 13% (p = NS); group 2, 57 +/- 4% versus 25 +/- 4% (p less than 0.001); and group 3, 77 +/- 5% versus 10 +/- 6% (p less than 0.0002). Compared with initial measurements, the 7E3 antibody was superior to aspirin in maintaining hyperemic coronary blood flow after release of the external stenosis: group 1, 177 +/- 14 versus 21 +/- 14 ml/min (p less than 0.0003); group 2, 189 +/- 9 versus 110 +/- 28 ml/min (p less than 0.008); and group 3, 194 +/- 12 versus 181 +/- 15 ml/min (p less than 0.02). In group 1, arterial occlusion developed in five dogs, and nonocclusive thrombus was seen in three dogs. In group 2, arterial occlusion developed in one dog, and nonocclusive thrombus was seen in five dogs. No thrombotic material was visualized in group 3 dogs treated with 7E3 F(ab')2. CONCLUSIONS In this animal model, the 7E3 antiplatelet antibody is superior to aspirin in inhibiting platelet aggregation, thrombosis, and acute closure after deep arterial injury caused by coronary balloon angioplasty.
Early Diagnosis of Nephroblastoma
Authors: R. B. Zachary, F. Harris
Journal: BMJ (1973)

Laboratories, Dr. Brian Scales), the usual therapeutic level being about 1.5 ug/ml.lTo our knowledge these are the highest values reported in man so far.Possibly any beta-blocker may cause heart failure in a patient whose myocardial per- formance depends critically on sympathetic drive.However, practolol seems to be less dangerous than others in this respect, and in normal therapeutic doses causes only modest reduction of cardiac output.2Practolol has been shown to possess some sympathomimetic activity.Its positive chronotropic activity may explain why the pulse rate fell relatively little and definite bradycardia did not occur in the case presented here.This may explain, partly at least, why the patient's heart condition did not deteriorate.Another possible explanation could be the less pro- nounced effect of practolol on myocardial contractility.This case illustrates the low toxicity of practolol and its modest cardiodepressive effect which has proved valuable in the treat- ment of patients with supraventricular arrhythmias and rapid ventricular rates after myocardial infarction and cardiac surgery.-We are, etc.,
GMC strikes off proponent of temporary brittle bone disease
Authors: Owen Dyer
Journal: BMJ (2004)

The General Medical Council last week struck off a pathologist who appeared as an expert witness for parents accused of injuring their children, after finding that he ignored crucial evidence to advance his own controversial theories on bone disease.

Colin Paterson, from Longforgan, near Dundee, was found to have failed in his duties as an expert witness in the trials of two sets of parents accused of harming their children.

In both cases, Dr Paterson told the court he believed the children's fractures were due to temporary brittle bone disease, a condition he himself first …
Randomized Trial of Tocilizumab in Systemic Juvenile Idiopathic Arthritis
Authors: Fabrizio De Benedetti, Hermine I. Brunner, Nicolino Ruperto, Andrew Kenwright, Stephen Wright, Inmaculada Calvo, Ruben Cuttica, Angelo Ravelli, Rayfel Schneider, Patricia Woo, Carine Wouters, Ricardo Xavier, Lawrence Zemel, Eileen Baildam, Ruben Burgos-Vargas, Pavla Dolezalova, Stella M. Garay, Rosa Merino, Rik Joos, Alexei Grom, Nico Wulffraat, Zbigniew Zuber, Francesco Zulian, Daniel Lovell, Alberto Martini
Journal: New England Journal of Medicine (2012)

Systemic juvenile idiopathic arthritis (JIA) is the most severe subtype of JIA; treatment options are limited. Interleukin-6 plays a pathogenic role in systemic JIA.We randomly assigned 112 children, 2 to 17 years of age, with active systemic JIA (duration of ≥6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids) to the anti-interleukin-6 receptor antibody tocilizumab (at a dose of 8 mg per kilogram of body weight if the weight was ≥30 kg or 12 mg per kilogram if the weight was <30 kg) or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients meeting the predefined criteria for nonresponse were offered open-label tocilizumab. All patients could enter an open-label extension.At week 12, the primary end point (an absence of fever and an improvement of 30% or more on at least three of the six variables in the American College of Rheumatology [ACR] core set for JIA, with no more than one variable worsening by more than 30%) was met in significantly more patients in the tocilizumab group than in the placebo group (64 of 75 [85%] vs. 9 of 37 [24%], P<0.001). At week 52, 80% of the patients who received tocilizumab had at least 70% improvement with no fever, including 59% who had 90% improvement; in addition, 48% of the patients had no joints with active arthritis, and 52% had discontinued oral glucocorticoids. In the double-blind phase, 159 adverse events, including 60 infections (2 serious), occurred in the tocilizumab group, as compared with 38, including 15 infections, in the placebo group. In the double-blind and extension periods combined, 39 serious adverse events (0.25 per patient-year), including 18 serious infections (0.11 per patient-year), occurred in patients who received tocilizumab. Neutropenia developed in 19 patients (17 patients with grade 3 and 2 patients with grade 4), and 21 had aminotransferase levels that were more than 2.5 times the upper limit of the normal range.Tocilizumab was efficacious in severe, persistent systemic JIA. Adverse events were common and included infection, neutropenia, and increased aminotransferase levels. (Funded by Hoffmann-La Roche; ClinicalTrials.gov number, NCT00642460.).
Eikenella Brain Abscess
Authors: Claude O. Burdick
Journal: JAMA (1982)

To the Editor.—  Eikenella corrodens is a gram-negative, facultatively anaerobic microorganism that is often a component of dental plaque and is present on 40% of healthy gums. The organism is usually nonpathogenic or weakly pathogenic. However, there have been a few reports, mostly in the dental literature, that describe important Eikenella infections. Most were associated with severe trauma, dental manipulation, or a depressed immune system. 1,2 Some drug abusers have experienced abscesses after using saliva to liquefy drugs before injection. 3   In a series of 41 Eikenella isolates obtained at UCLA and Wadsworth Hospital Center, Los Angeles, from 1974 through 1977, there were no isolates from brain abscesses. 4 Recently, we have seen a patient with a large brain abscess caused by Eikenella who had no predisposing illness or dental surgery.  Report of a Case.—  A 38-year-old man had been in excellent health. Two weeks before hospital admission, he experienced
Adeno-associated Virus 2-Mediated Transduction and Erythroid Lineage-Restricted Long-Term Expression of the Human β-Globin Gene in Hematopoietic Cells from Homozygous β-Thalassemic Mice
Authors: Mengqun Tan, Keyun Qing, Shangzhen Zhou, Mervin C. Yoder, Arun Srivastava
Journal: Molecular Therapy (2001)

Adeno-associated virus 2 (AAV), a nonpathogenic human parvovirus, has gained attention as a potentially useful vector for human gene therapy. Here, we report successful AAV-mediated stable transduction and high-efficiency, long-term, erythroid lineage-restricted expression of a human β-globin gene in primary murine hematopoietic stem cells in vivo. Bone marrow-derived primitive Sca-1+, lin− hematopoietic stem cells from homozygous β-thalassemic mice were transduced ex vivo with a recombinant AAV vector containing a normal human β-globin gene followed by transplantation into low-dose-irradiated B6.c-kitW41/41 anemic recipient mice. Six months posttransplantation, tail-vein blood samples were analyzed by PCR amplification to document the presence of the transduced human β-globin gene sequences in the peripheral blood cells. Semiquantitative PCR analyses revealed that the transduced human β-globin gene sequences were present at ∼1 copy per cell. The efficiency of the human β-globin gene expression was determined to be up to 35% compared with the murine endogenous β-globin gene by semiquantitative RT-PCR analyses. Peripheral blood samples from several positive recipient mice obtained 10 months posttransplantation were fractionated to obtain enriched populations of granulocytes, lymphocytes, and erythroid cells. PCR analyses revealed the presence of the human β-globin gene sequences in granulocytes and lymphocytes, indicating multilineage reconstitution. However, only the erythroid population was positive following RT-PCR analyses, suggesting lineage-restricted expression of the transduced human β-globin gene. Southern blot analyses of total genomic DNA samples isolated from bone marrow cells from transplanted mice also documented proviral integration. These results provide further support for the potential use of recombinant AAV vectors in gene therapy of β-thalassemia and sickle-cell disease.
Adipose Tissue Detected by Multislice Computed Tomography in Patients After Myocardial Infarction
Authors: Yasutaka Ichikawa, Kakuya Kitagawa, Shuji Chino, Masaki Ishida, Koji Matsuoka, Takashi Tanigawa, Tomoaki Nakamura, Tadanori Hirano, Kan Takeda, Hajime Sakuma
Journal: JACC. Cardiovascular imaging (2009)
Sir Thomas Browne (1605-1682)
Authors: C. S Breathnach
Journal: Journal of the Royal Society of Medicine (2005)

There is no man more Paradoxical than myself'.Four hundred years after his birth, Sir Thomas Browne (Figure 1) is remembered not for his metaphysical subtleties or scientific speculations but for his unfailing toleration in an age of sectarian strife.Thomas was the youngest of four children of a mercer,
Tocolytics: do they actually work?
Authors: Z. Alfirevic
Journal: BMJ (2012)

Never mind “which one works?” We still don’t know if delaying delivery is safe

In a linked research paper (doi:10.1136/bmj.e6226), Haas and colleagues assessed the relative effectiveness of various tocolytic drugs aimed at preventing preterm birth.1 Being born too early may have serious detrimental effects on health. It is hardly surprising that extremely preterm children, born before 26 weeks’ gestation, who survive to school age have significantly lower scores for cognitive ability, reading, and mathematics.2 However, even babies born a few weeks before term are more likely to underperform on most measures of general health than their peers born at term.3 With an estimated 14.9 million babies born preterm each year (11.1% of all live births worldwide), the burden of preterm births on families and healthcare systems in high income and low income countries is considerable.4 It is important to remember that some preterm births are iatrogenic. They are a consequence of labour induction or prelabour caesarean sections, which are often life saving interventions for mother and baby, particularly in severe pre-eclampsia, intrauterine growth restriction, or placental abruption. Such iatrogenic preterm births should be …
SAPS 3 scores at the start of renal replacement therapy predict mortality in critically ill patients with acute kidney injury
Authors: Elizabeth Maccariello, Carla Valente, Lina Nogueira, Helio Bonomo, Marcia Ismael, Jose Eduardo Machado, Fernanda Baldotto, Marise Godinho, Ricardo Valença, Eduardo Rocha, Marcio Soares
Journal: Kidney International (2009)
Phosphodiesterase 3 inhibitors suppress oocyte maturation and consequent pregnancy without affecting ovulation and cyclicity in rodents.
Authors: A Wiersma, B Hirsch, A Tsafriri, R G Hanssen, M Van de Kant, H J Kloosterboer, M Conti, A J Hsueh
Journal: Journal of Clinical Investigation (1998)

During each reproductive cycle, a preovulatory surge of gonadotropins induces meiotic maturation of the oocyte in the preovulatory follicle followed by ovulation. Although gonadotropins stimulate cAMP production in somatic cells of the follicle, a decrease in intra-oocyte cAMP levels is required for resumption of meiosis in oocytes. Based on the observed compartmentalization of the cAMP-degrading enzyme, phosphodiesterase, in follicular somatic and germ cells, inhibitors of phosphodiesterase 3 were used to block meiosis in ovulating oocytes in rodents. By this strategy, we demonstrated that fertilization and pregnancy could be prevented without disturbing follicle rupture and normal estrous cyclicity. In contrast to conventional contraceptive pills that disrupt ovarian steroidogenesis and reproductive cycles, the present strategy achieves effective contraception by selective blockage of oocyte maturation and development without alterations in ovulation and reproductive cyclicity.
Oral exposure to Mal d 1 affects the immune response in patients with birch pollen allergy
Authors: Marija Geroldinger-Simic, Tamar Kinaciyan, Birgit Nagl, Ursula Baumgartner-Durchschlag, Hans Huber, Christof Ebner, Jonas Lidholm, Detlef Bartel, Stefan Vieths, Beatrice Jahn-Schmid, Barbara Bohle
Journal: Journal of Allergy and Clinical Immunology (2012)
Wales to reform psychiatric care for children
Authors: R. Dobson
Journal: BMJ (1999)

New safeguards to protect children in psychiatric hospitals throughout Wales have been proposed by the Welsh secretary, Alun Michael. A strategic review of psychiatric services will also be undertaken after an independent inquiry into inpatient care for young people pinpointed several problem.

The inquiry, carried out by the Hospital Advisory Service 2000,was set up after the north Wales child …
RECENT CONTRIBUTIONS TO THE UNDERSTANDING OF EXPERIMENTAL DIABETES
Authors: DeWitt Stetten
Journal: JAMA (1952)

To the biochemist the living organism is a complex, highly organized, heterogeneous system of compounds displaying a high degree of chemical activity. Despite this activity, it is striking that the chemical composition of the several tissues of the normal adult animal remains fairly constant. It is today recognized that in many instances this constancy of composition is not attributable to thermodynamic equilibrium or to kinetic stability. In general, in the living animal the organic reactions that comprise intermediary metabolism take place far from the equilibrium point, and the molecules of substrate, activated in most cases by enzymes, have far less stability than do the same compounds in pure form in bottles on the shelf. Thus glucose, undergoing no measurable decay at 37 C in the pure state, will, in the presence of animal tissues, rapidly disappear. The constancy of composition of body fluids and tissues with respect to many organic
Human induced CD4+CD25+FOXP3+ regulatory T cells are suppressive in vitro, but fail to suppress inflammation in vivo
Authors: Y. Vercoulen, T. Guichelaar, J. Meerding, M. Emmelot, M. Pingen, W. de Jager, T. Mutis, A. Martens, P. Coffer, B. Prakken
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Regulatory T cells (Treg) are important to maintain immune homeostasis. Presence of Treg correlates with a favourable disease course in juvenile idiopathic arthritis (JIA) patients. A distinction within the Treg population can be made between naturally occurring Treg (nTreg), which are derived from the thymus, and peripherally induced Treg (iTreg). Induction of Treg in the periphery is a promising way to modulate diseases like JIA, since it is easier to obtain high numbers of cells. However, the functionality of activation-induced CD4<sup>+</sup>CD25<sup>+</sup>FOXP3<sup>+</sup> Treg has been highly debated in the last few years. Furthermore, in vivo induction of Treg by TCR or co-stimulation could induce a cytokine storm. Therefore, it is important to carefully monitor iTreg functionality. <h3>Objectives</h3> In this study, the authors tested whether human iTreg suppress immune responses in vitro, and in vivo in a humanised mouse model of xenogeneic graft versus host disease (x-GvHD). <h3>Methods</h3> CD4<sup>+</sup>CD25<sup>−</sup> T cells were isolated from human PBMC and cultured with aCD3/aCD28 with or without interleukin-2 and TGFβ to obtain iTreg. CD4<sup>+</sup>CD25<sup>high</sup> T cells were cultured with αCD3/αCD28, interleukin-2 and TGFβ to obtain nTreg. Supernatant was taken for Luminex analysis and cells were stained for Treg markers. Suppression assays were performed to determine suppressive capacity. RAG<sup>−/−</sup> γc<sup>−/−</sup> mice were sublethally irradiated and injected with clodronate liposomes to deplete phagocyting cells. Next, human PBMC were injected with or without iTreg or nTreg from the same human donor. Mice were scored for x-GvHD during 9 weeks. <h3>Results and conclusions</h3> The authors show here that induced Treg FOXP3 expression levels and suppressive capacity in vitro were comparable to nTreg. As expected, nTreg efficiently prevented acute x-GvHD. However, in contrast with nTreg, iTreg did not suppress disease. The results show that polyclonally induced Treg display no suppressive capacity in x-GvHD, due to a quick loss of FOXP3 in vivo. This underscores the importance to use humanised mouse models for validation of data regarding iTreg function obtained in in vitro assays, before proceeding to application in patients.
Liver disease in children with pizz α1-antitrypsin deficiency
Authors: Fayez K. Ghishan, Harry L. Greene
Journal: Hepatology (1988)

We present our experience with 18 pediatric patients with alpha 1-antitrypsin deficiency of the PiZZ phenotype. Fifteen patients (83%) presented with neonatal cholestatic jaundice at a mean age of 2 +/- 0.6 months (+/- S.D.). The male:female ratio was 15:3, indicating a male predominance. All metabolic, infectious and obstructive causes of jaundice were ruled out by appropriate tests in the patients with neonatal cholestasis. Liver biopsy in 14 patients with neonatal cholestasis showed a histological picture of cholestasis in all biopsies; neonatal giant cell hepatitis appeared in seven, increased fibrosis in appeared five and established liver cirrhosis appeared in two biopsies. Patients were followed for a mean of 3.7 +/- 2.4 years (+/- S.D.). Of the 15 patients with neonatal cholestasis, 3 under went liver transplantation because of decompensated liver cirrhosis at 3, 3 1/2 and 7 years. Two patients died at 4 months and 3 years from complications of liver cirrhosis. Of the remaining 10 patients, 3 had histological evidence of liver cirrhosis, and the remaining 7 patients continue to have enlarged liver and spleen with abnormal liver function tests. Of the three patients without history of neonatal cholestasis, only one had enlarged liver and spleen, and the remaining two are healthy with normal liver function tests. Our experience indicates serious liver disease is highly likely to develop in patients with PiZZ alpha 1-antitrypsin deficiency who present with neonatal cholestatic jaundice. Our experience differs from more recent reports on such patients.
Biopsy of abdominal masses guided by ultrasound.
Authors: D Slater
Journal: BMJ (1990)

the agents gave advice on relevant immunisations and malaria prophylaxis.Nineteen agents recog- nised that there was a risk of acquiring HIV infection in Bangkok, but only four of these advised customers of that risk.The Department of Health booklet The Travel- lers Guide to Health contains information on HIV infection and the measures to take to avoid infection.2This booklet was available in 18 of the agencies: for reference only in two, on request in 11, and given to all booking customers in five.We were concerned to discover that two commonly quoted reference sources ABC Guide to Inter- national Travel1 and World Travel Guide' did not mention the risk of HIV infection to travellers.We recommend that the Department of Health book- let should be readily available to all travellers.Though we recognise worldwide distribution of HIV and that the risk of infection relates to particular activities and not to the area per se, perhaps known high risk areas should be identified specifically.Clearly, travel agents already assume some responsibility for providing health informa- tion to travellers.We suggest that this should be extended to include advice about the risks of contracting HIV while abroad and ways to minimise this risk.
P3-07-27: ROCK II Expression Can Be a Potential Marker of Non-Sentinel Lymph Node Metastasis in Breast Cancer Patients with Sentinel Lymph Node Involvement.
Authors: H Shigematsu, K Taguchi, S Shiotani, H Kawaguchi, K Nishiyama, S Ohno, M Okada
Journal: Cancer Research (2011)

Abstract (Background) It becomes controversy whether axillary lymph node dissection is mandatory performed for breast cancer patients with positive sentinel lymph nodes (SNs), given that more than half of patients with a positive sentinel lymph biopsy have no metastasis in non-sentinel lymph nodes (non-SNs). Rho-associated kinase (ROCK) is essential part in tumor invasion and metastasis, and its activation is reported to be potential marker of lymph node metastasis. (Purpose) The purpose of this study was to evaluate the expression of ROCK II as predictive factor of non-SNs metastasis in breast cancer patients with positive SNs. (Patients and Method) ROCK II protein expression was determined using immunohistochemical analysis on formalin-fixed and paraffin-embedded primary tumor samples composed of 119 SN-positive patients who underwent axillary lymph node dissection in National Kyushu Cancer Center. ROCK II expression was defined positive when there was strong intensity of cytoplasm staining. (Results) ROCK II expression tended to be strong in invasive area, but weak in intraductal component. Of the 119 patients, 35 (29%) were determined to be positive for ROCK II expression. Patients with ROCK II positive tumor had significantly higher probability of non-SNs metastasis compared with patients with ROCK II negative tumor (20/35, 57% for positive; 28/84, 33% for negative, p=0.02). In multivariate analysis, positive ROCK II expression was significantly associated with non-SNs metastasis even after accounting for other predictive factors including tumor size, lymphovascular invasion, number of SNs metastasis and extra-capsule invasion (positive vs. negative, HR 2.6, p=0.04). (Conclusion) These findings suggest that ROCK II expression can be a predictive factor for non-SNs involvement in breast cancer patients with SNs metastasis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-27.
Use of Prenatal Cytogenetic Diagnosis in New York State
Authors: Ernest B. Hook, Dina M. Schreinemachers, Philip K. Cross
Journal: New England Journal of Medicine (1981)

Since 1975, when the National Institutes of Health announced the safety and efficacy of prenatal diagnosis,1 there has been a marked increase in the use of this procedure. Here we review such use in New York State. To our knowledge, this is the first such estimate for a heavily populated civil jurisdiction in which use can be analyzed by geographical area. The analyses also illustrate the utility of data from a chromosome registry in determining the delivery of genetic services.MethodsThe New York State Chromosome Registry has been in existence since 1968. To our knowledge, this is the only . . .