tbuckley/cabot-search huggingface dataset:
Identifying the genes for diabetes and schizophrenia
Authors: E. Feldman
Journal: BMJ (1991)

specimen showed greatly increased cellularity with a blast cell infiltrate typical of acute myeloblastic leukaemia.Immunophenotyping (HLA-DR 85%, CD34 84%, CD13 81%, CD33 74%, CD7 55%, Tdt 40% positive) was consistent with a primitive acute myeloblastic leukaemia.Cytogenetic analysis showed a 45XY, -5, -7 karyotype with multiple clonal abnormalities typical of secondary acute myeloblastic leukaemia.The patient died two months later.Postmortem examination was not performed.Like many heavily treated patients with lymphoma (or other cancer) our patient was at risk of developing secondary acute myeloblastic leukaemia.2In this disease the cells are known to express receptors for granulocyte colony stimulating factor.The temporal relation between the start of treatment with recombinant granulocyte colony stimulating factor and the development of leukaemia is disturbing.The case indicates that the statement by Drs Khwaja and Goldstone above may, unfortunately, already require modification.As the use of haemopoietic growth factors rises clinicians should be aware of their adverse, as well as beneficial, effects.
The Conjoint Board in England and the Five Years Curriculum
Authors: L. Atthill
Journal: BMJ (1901)

The management of hand injuries forms an important part of the hospital accident and emergency service, and early recognition and informed management are essential for a favourable outcome (Frazier et al., 1978). In Edinburgh a routine system of hand management is well established and includes the training of casualty officers. In order to evaluate the effectiveness of the hand service in the Accident and Emergency Department, Royal Infirmary of Edinburgh, a prospective study was undertaken to compare the outcome of treatment of hand injury by a routine system with treatment over a similar period by more experienced registrars in hand surgery training posts (Hand Fellows).
Creation of an atrial septal defect in transposition of the great vessels.
Authors: M S Gotsman
Journal: Thorax (1965)

Four-fifths of the infants with transposition of the great vessels die within the first year of life (Abbott, 1936).Fifty-two per cent.die within the first month and 86% are dead within six months (Keith, Neill, Viad, Rowe, and Chute, 1953).This lesion in some form occurs in 20% of necropsies on patients with congenital heart disease (Keith, Rowe, and Vlad, 1958).In Birmingham, trans- position of the great vessels is the commonest form of cyanotic congenital heart disease in patients admitted to the neonatal cardiac unit.The outcome is frequently fatal.The prognosis is worse if a ventricular septal defect is absent (Noonan, Nadas, Rudolph, and Harris, 1960) and the atrial septal defect is small (Mustard, Keith, Trusler, Fowler, and Kidd, 1964).Any form of therapy is therefore useful if it can prolong life until the patient has grown sufficiently to benefit from corrective sur.gery.Hanlon and Blalock (1948) and Fontana and Edwards (1962) found that the duration of survival is longest when both atrial and ventricular septal defects are present.The creation of an atrial septal defect therefore appears to be a rational form of palliative therapy (Ochsner, Cooley, Harris, and McNamara, 1961 Mustard, 1964; Mustard et al., 1964; Trusler, Mustard, and Fowler, 1964).Unfortunately, no detailed haemodynamic reports are available to indicate the effectiveness of creating an atrial septal defect, since cardiac catheterization in this group of patients is difficult and dangerous.We shall describe the findings at cineangiocardiography before and after the creation of an atrial septal defect in a seriously ill neonate who improved after operation. CASE REPORTA.C.. a second child, was born at home at full term.Cyanosis was noted at birth.
Combined SFK/mTOR Inhibition Prevents Rapamycin-Induced Feedback Activation of AKT and Elicits Efficient Tumor Regression
Authors: Jennifer L. Yori, Kristen L. Lozada, Darcie D. Seachrist, Jonathan D. Mosley, Fadi W. Abdul-Karim, Christine N. Booth, Chris A. Flask, Ruth A. Keri
Journal: Cancer Research (2014)

Abstract Resistance to receptor tyrosine kinase (RTK) blockade in breast cancer is often mediated by activation of bypass pathways that sustain growth. Src and mammalian target of rapamycin (mTOR) are two intrinsic targets that are downstream of most RTKs. To date, limited clinical efficacy has been observed with either Src or mTOR inhibitors when used as single agents. Resistance to mTOR inhibitors is associated with loss of negative feedback regulation, resulting in phosphorylation and activation of AKT. Herein, we describe a novel role for Src in contributing to rapalog-induced AKT activation. We found that dual activation of Src and the mTOR pathway occurs in nearly half of all breast cancers, suggesting potential cross-talk. As expected, rapamycin inhibition of mTOR results in feedback activation of AKT in breast cancer cell lines. Addition of the Src/c-Abl inhibitor, dasatinib, completely blocks this feedback activation, confirming convergence between Src and the mTOR pathway. Analysis in vivo revealed that dual Src and mTOR inhibition is highly effective in two mouse models of breast cancer. In a luminal disease model, combined dasatinib and rapamycin is more effective at inducing regression than either single agent. Furthermore, the combination of dasatinib and rapamycin delays tumor recurrence following the cessation of treatment. In a model of human EGFR-2–positive (HER2+) disease, dasatinib alone is ineffective, but potentiates the efficacy of rapamycin. These data suggest that combining mTOR and Src inhibitors may provide a new approach for treating multiple breast cancer subtypes that may circumvent resistance to targeted RTK therapies. Cancer Res; 74(17); 4762–71. ©2014 AACR.
Anaesthetist urges caution over adopting safety strategies from high risk industries
Authors: R. Coombes
Journal: BMJ (2014)

Doctors should think twice before rushing to learn lessons from aviation and other high risk industries, a leading anaesthetist has warned.

Kevin Fong, a consultant anaesthetist at University College London, currently seconded to Kent, Surrey, and Sussex Air Ambulance Service, said that aviation’s “brilliant” safety record did hold many lessons for medicine but that the comparisons went only so far. Fong, who has also worked at NASA in the United States, called for expert “translators” to work between industries to bring lessons of safety across to healthcare.

“When sharing lessons from other systems you can fall very quickly into false equivalence,” he said. “We are only now beginning to …
Chronic obstructive pulmonary disease
Authors: D. Price
Journal: BMJ (2003)

Three distinct disorders combine to produce chronic obstructive pulmonary disease (COPD): emphysema, peripheral airway disease or bronchospasm, and chronic bronchitis.


Chronic obstructive pulmonary disease is defined as a disease state characterized by airflow limitation that is not fully reversible.


Cigarette smoking is the major cause of COPD in both men and women in the United States.


The most important familial factor associated with COPD is α1-antiprotease deficiency (i.e., α1-antitrypsin deficiency).


With exercise, the arterial PO2 may rise minimally or fall in patients with COPD.


The pulmonary function testing remains the standard in the initial evaluation of patients with COPD.


In COPD, the forced expiratory volume (FEV), and maximal expiratory flow at 50% and 75% of vital capacity are reduced.


Smoking cessation is the first and most important clinical intervention.


Long-term oxygen therapy prolongs survival in selected patients with COPD.


Lung transplantation therapy with a single lung is feasible in patients with COPD.
The Immunobiology of Abortion
Authors: Richard T. Smith
Journal: New England Journal of Medicine (1976)

How is the fetus permitted 270 days of intrauterine life by the same mother who will promptly reject fetal or paternal tissues grafted at any other site? Intensive research effort during the past 20 years has yielded much new information, but this immunologic enigma remains unresolved. A fresh insight into the issue appears to be provided through the findings of Rocklin et al. in an immunologic study of unsuccessful gestation reported in this issue of the Journal (p. 1209). They show that a paternal antigen-specific lymphocyte blocking factor normally found in maternal serum is absent in women who have had . . .
A histone deacetylase inhibitor, trichostatin A, suppresses myofibroblastic differentiation of rat hepatic stellate cells in primary culture
Authors: Toshiro Niki, Krista Rombouts, Pieter De Bleser, Karen De Smet, Vera Rogiers, Detlef Schuppan, Minoru Yoshida, Giulio Gabbiani, Albert Geerts
Journal: Hepatology (1999)

Hepatic stellate cells are the major cellular sources of extracellular matrix in chronic liver diseases leading to fibrosis. We explored the antifibrogenic effect of two histone deacetylase inhibitors, sodium butyrate and trichostatin A (TSA), on this cell type in vitro. Primary hepatic stellate cells as well as culture activated cells were exposed to butyrate (0.01–1 mmol/L) or TSA (1–100 nmol7sol;L); their effect on collagen types I and III and smooth muscle α–actin was examined by quantitative immunoprecipitation and by Northern analysis. Their antiproliferative effect was examined by 3 H–thymidine incorporation and cell counting. Hyperacetylation of histones was demonstrated by acid urea/Triton–X–100 (AUT) polyacrylamide gel electrophoresis. Possible cytotoxic effects were judged on stellate cells by evaluating de novo total protein synthesis, and on hepatocytes by measuring lactate dehydrogenase (LDH) leakage, albumin secretion, and epoxide hydrolase and ethoxycoumarin O –deethylase activity. TSA at 100 nmol/L and butyrate at 1 mmol/L retarded the morphological changes characteristic for activation of primary stellate cells. TSA at 100 nmol/ inhibited synthesis of collagen types I and III and smooth muscle α–actin by 62%, 70%, and 88%. Butyrate at 1 mmol/L showed a modest inhibitory effect on collagen type III and smooth muscle α–actin, but had no effect on collagen type I. Northern analysis suggested that these inhibitory effects on collagen type III and smooth muscle α–actin were transcriptional, while the effect on collagen type I was largely posttranscriptional. At 100 nmol/L, TSA strongly suppressed proliferation of primary hepatic stellate cells. Inhibition of activation of stellate cells was preceded by hyperacetylation of histone H4. When tested on cells at day 14 in culture, butyrate had no inhibitory effects on the synthesis of collagens or smooth muscle α–actin. One hundred or 10 nmol/L TSA modestly inhibited the synthesis of collagens type I (-24%,-22%) and III (-34%,-22%), and smooth muscle α–actin (-27%,-12%). We conclude that TSA inhibits transdifferentiation of stellate cells into myofibroblasts by interfering with the level of acetylation of histone H4.
Pseudomonas aeruginosa infection in human immunodeficiency virus infected patients
Authors: Jean-Luc Meynard, Frédéric Barbut, Marguerite Guiguet, Dominique Batissel, Valérie Lalande, Danièle Lesage, Jean-Baptiste Guiard-Schmid, Jean-Claude Petit, Jacques Frottier, Marie-Caroline Meyohas
Journal: Journal of Infection (1999)
Primary care opportunities and threats: developing prescribing in primary care
Authors: C. P Bradley, R. J Taylor, A. Blenkinsopp
Journal: BMJ (1997)

The latest white papers on the NHS focus on stimulating innovation in the delivery of primary care and removing barriers to further development. Some of this innovation relates directly to prescribing in primary care, and in this article the authors speculate on what might happen if the prescribing initiatives referred to in the white papers were extended and disseminated more widely. The initiatives which might have the biggest impact are those encouraging closer collaboration between general practitioners and community pharmacists and those aiding extension of the current nurse prescribing scheme in primary care. Both offer considerable opportunities to improve primary care, but both bear some potential risks.
A STUDY OF A CASE OF GREEN URINERESULTING FROM THE ADMINISTRATION OF METHYLENE BLUE IN A PROPRIETARY REMEDY.
Authors: JAMES M. COOPER
Journal: JAMA (1904)

While cases of green urine are by no means unknown, the circumstances surrounding a recent case are so much out of the ordinary that they will interest the general practitioner. On the other hand, the report will not be without scientific interest and value, since one of the foremost American text-books on diagnosis, in speaking of this condition, dismisses the subject with the statement that, "while green urines have been described, the cause of the color has not been definitely ascertained." <h3>THE CASE REPORTED.</h3> On Dec. 1, 1903, there was submitted to me for examination about 120 c.c. of urine of a bright grass-green color, and possessing a peculiar aromatic odor, not unlike that of oil of juniper or wintergreen. The patient was a woman, 76 years of age, who had been for a long time troubled with sciatic rheumatism, for which she had tried numerous remedies, but with little
Implications of the Mental Health Parity and Addiction Equity Act
Authors: Susan H. Busch
Journal: American Journal of Psychiatry (2012)

The Mental Health Parity and Addiction Equity Act (MHPAEA) mandates equity in insurance coverage, including both treatment limits (caps on inpatient days and out-patient visits) and financial requirements (cost sharing, deductibles, and out-of-pocket limits), for behavioral health and medical/surgical services.Some insurers and employers, however, have voiced concerns that implementation of the MHPAEA will lead to larger cost increases than those found in previous studies of parity.Generally, these studies have found that parity can be achieved with few if any increases in total health care costs (1).The new federal law goes further than most previous laws by extending parity to managed care techniques that may not be expressed numerically but may nevertheless limit the scope or duration of services-so-called nonquantitative treatment limitations.These management techniques include requirements such as prior authorization, utilization review, or standards for provider participation in a network.Under the new federal law, insurance plans must use the same processes or strategies that they use for medical/surgical benefits to determine how nonquantitative treatment limitations are set.Because some studies suggest that these management techniques are what allowed parity to occur without large cost increases in the past (2), there are concerns that the new federal law would lead to relatively large cost increases.However, there is no published direct evidence to date on the effect of the MHPAEA on health care costs.
FREE MALARIAL PARASITES AND THE EFFECT OF THE MIGRATION OF THE PARASITES OF TERTIAN MALARIAL INFECTIONS
Authors: Mary R. Lawson
Journal: The Journal of Experimental Medicine (1914)

1. The malarial parasite is extracellular throughout its life cycle and migrates from red corpuscle to red corpuscle destroying each before it abandons it; in the brief intervals between, the parasite is free in the blood serum; it does not remain long free, but almost immediately attaches itself to another red corpuscle by means of delicate pseudopodia. 2. The compact form of the tertian parasite is the type of free parasite most often observed; in this form the parasite may be seen not only in migration, but after quinine and in the cadaver. I believe the compact form to be the normal resting form of the parasite, all other forms being assumed in order to secure attachment and to obtain food. 3. Care must be taken not to confound free parasites having protoplasmic pseudopodia ready for attachment with the sexual flagellating parasites, whose flagella are composed of chromatin. 4. The malarial parasite can live for some time free in the blood serum, though under normal conditions there is no reason why it should remain free for any length of time, and there are certain periods in the life of the parasite when it must be admitted that it is free from the corpuscle and survives. If the parasite is, as I believe, attached to the external surface of the red corpuscle, it is constantly exposed to the action of the patients' serum. 5. The destruction of more than one red corpuscle by each parasite would readily account for the severe and early anemia occurring in malarial infections. 6. Long continued treatment with quinine will eventually cause the death of all malarial parasites.
Helicobacter pylori Eradication to Prevent Gastric Cancer in a High-Risk Region of China
Authors: Benjamin Chun-Yu Wong, Shiu Kum Lam, Wai Man Wong, Jian Shun Chen, Ting Ting Zheng, Rui E. Feng, Kam Chuen Lai, Wayne Hsing Cheng Hu, Siu Tsan Yuen, Suet Yi Leung, Daniel Yee Tak Fong, Joanna Ho, Chi Kong Ching, Jun Shi Chen, None for the China Gastric Cancer Study Group
Journal: JAMA (2004)

Although chronic Helicobacter pylori infection is associated with gastric cancer, the effect of H pylori treatment on prevention of gastric cancer development in chronic carriers is unknown.To determine whether treatment of H pylori infection reduces the incidence of gastric cancer.Prospective, randomized, placebo-controlled, population-based primary prevention study of 1630 healthy carriers of H pylori infection from Fujian Province, China, recruited in July 1994 and followed up until January 2002. A total of 988 participants did not have precancerous lesions (gastric atrophy, intestinal metaplasia, or gastric dysplasia) on study entry.Patients were randomly assigned to receive H pylori eradication treatment: a 2-week course of omeprazole, 20 mg, a combination product of amoxicillin and clavulanate potassium, 750 mg, and metronidazole, 400 mg, all twice daily (n = 817); or placebo (n = 813).The primary outcome measure was incidence of gastric cancer during follow-up, compared between H pylori eradication and placebo groups. The secondary outcome measure was incidence of gastric cancer in patients with or without precancerous lesions, compared between the 2 groups.Among the 18 new cases of gastric cancers that developed, no overall reduction was observed in participants who received H pylori eradication treatment (n = 7) compared with those who did not (n = 11) (P =.33). In a subgroup of patients with no precancerous lesions on presentation, no patient developed gastric cancer during a follow-up of 7.5 years after H pylori eradication treatment compared with those who received placebo (0 vs 6; P =.02). Smoking (hazard ratio [HR], 6.2; 95% confidence interval [CI], 2.3-16.5; P<.001) and older age (HR, 1.10; 95% CI, 1.05-1.15; P<.001) were independent risk factors for the development of gastric cancer in this cohort.We found that the incidence of gastric cancer development at the population level was similar between participants receiving H pylori eradication treatment and those receiving placebo during a period of 7.5 years in a high-risk region of China. In the subgroup of H pylori carriers without precancerous lesions, eradication of H pylori significantly decreased the development of gastric cancer. Further studies to investigate the role of H pylori eradication in participants with precancerous lesions are warranted.
Roles of RabGEF1/Rabex-5 domains in regulating FcϵRI surface expression and FcϵRI-dependent responses in mast cells
Authors: Janet Kalesnikoff, Eon J. Rios, Ching-Cheng Chen, M. Alejandro Barbieri, Mindy Tsai, See-Ying Tam, Stephen J. Galli
Journal: Blood (2007)
Physician Continuity Improves Outcomes for Heart Failure Patients Treated and Released From the Emergency Department
Authors: Robinder S. Sidhu, Erik Youngson, Finlay A. McAlister
Journal: JACC Heart Failure (2014)

The goal of this study was to evaluate the effect of physician continuity for patients with heart failure (HF) treated and released from the emergency department (ED). Although current guidelines recommend early follow-up after hospital discharge, it is unclear if it is beneficial in patients sent home from the ED and whether this follow-up should be with a familiar physician. This was a retrospective cohort of all adults treated and released from 93 EDs in Alberta, Canada, from 1999 to 2009 with a first-time most responsible diagnosis of HF. Cox proportional hazards models with time-varying covariates for post-ED outpatient visits were used. In 12,285 patients (mean age 74.9 years), the rate of death or all-cause hospitalization at 6 months was lower in those who saw a familiar physician (37.3%; adjusted hazard ratio [aHR]: 0.89 [95% confidence interval (CI): 0.83 to 0.96]) in the first month versus those with no outpatient visits (58.1%; aHR: 1.00 [referent]) or visits only with unfamiliar physicians (40.2%; aHR: 1.04 [95% CI: 0.94 to 1.15]). Taking into account all outpatient visits over each observation period and excluding those without follow-up, death or hospitalization was less common in those patients being followed up by a familiar physician (aHR of 0.79 [95% CI: 0.71 to 0.89] at 3 months; aHR of 0.86 [95% CI: 0.77 to 0.95] at 6 months; and aHR of 0.87 [95% CI: 0.80 to 0.96] at 12 months compared with unfamiliar physician follow-up). Any follow-up within 30 days of ED release was associated with a lower risk of repeat ED visit or death at 6 months (aHR: 0.78 [95% CI: 0.73 to 0.82] for familiar physicians; aHR: 0.79 [95% CI: 0.72 to 0.86] for unfamiliar physicians). Early follow-up after an ED visit is associated with better outcomes, particularly if conducted with a familiar physician.
Chronic Myeloid Leukemia — Advances in Biology and New Approaches to Treatment
Authors: John M. Goldman, Junia V. Melo
Journal: New England Journal of Medicine (2003)

An extraordinary series of discoveries about chronic myeloid leukemia (CML) has made this disease a model of the way in which bench and bedside research can unite and culminate in clinically important advances. This review brings the reader up to date on recent advances in understanding the biology of CML and how they have changed the management of the disease.
Sclerosing lymphangitis of the penis: a lymphangiofibrosis thrombotica occlusiva*
Authors: WOLFGANG CH. MARSCH, GUNTER STUTTGEN
Journal: British Journal of Dermatology (1981)

Journal Article Sclerosing lymphangitis of the penis: a lymphangiofibrosis thrombotica occlusiva Get access WOLFGANG CH. MARSCH, WOLFGANG CH. MARSCH Department of Dermatology, Free University of Berlin, Rudolf Virchow‐Hospital, Berlin, Germany Reprint requests: Dr Wolfgang Ch, Marsch, Department of Dermatoiogy, Free University of Berlin, Rudolf Virchow‐Hospital, Augustenburger Platz 1, D‐1000 Berlin 65, Germany. Search for other works by this author on: Oxford Academic Google Scholar GÜNTER STÜTTGEN GÜNTER STÜTTGEN Department of Dermatology, Free University of Berlin, Rudolf Virchow‐Hospital, Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 104, Issue 6, 1 June 1981, Page 687, https://doi.org/10.1111/j.1365-2133.1981.tb00757.x Published: 01 June 1981 Article history Accepted: 02 May 1980 Published: 01 June 1981