tbuckley/cabot-search huggingface dataset:
New antifungal and antiviral chemotherapy.
Authors: J C Stewart, J Ferguson, P Davey
Journal: BMJ (1983)

Antifungal chemotherapySuperficial fungal infections caused by dermatophytes and yeasts are among the commonest cutaneous diseases.For- tunately, in the United Kingdom systemic fungal infections are rare, although their incidence in recent years has been increased by opportunistic infection in immunosuppressed patients.Despite this increase in systemic infections the development of effective antifungal drugs has lagged well behind that of antibiotics, at least in part because fewer differences in cell type exist between the eukaryotic fungal pathogen and host than between the prokaryotic bacterial pathogen and host.Until 1970 there were a few antifungal drugs, which had certain limitations including toxicity, narrow spectrum of activity, parenteral administration, and commonly a failure to cure.With the advent of the imidazole derivatives a major new class of antifungal drugs has emerged which combines low toxicity and versatility of administration with a wide spectrum of antifungal action against dermatophytes, yeasts, and dimorphic fungi. IMIDAZOLESThe precise mechanism of action of the imidazoles is not known but one important effect may be the inhibition of the synthesis of ergosterol.This is an essential component of fungal plasma membranes which is not required by mammals.Ad- ditionally, imidazoles inhibit the transformation of candidal yeast to hyphal forms which renders the organism more sus- ceptible to phagocytosis by host leucocytes.These diverse effects may explain the broad spectrum of the imidazoles and the rarity of drug resistant strains.Although the antifungal properties of this group were known 40 years ago, their development for clinical use has taken place only over the past 15 years, initially with clotrimazole, miconazole, and more recently with econazole, isoconazole, and ketoconazole.These drugs are reviewed according to their route of administration. Topical applicationClotrimazole (Canesten), econazole (Ecostatin, Gyno-Pevaryl), and miconazole (Daktarin, Dermonistat, and Monistat) are available as creams, pessaries, and vaginal tablets.Dusting powders and spray are also available for the treatment of skin
New treatment for bile salt malabsorption
Authors: J Puleston
Journal: Gut (2005)

Currently available binding resins used for symptomatic bile salt malabsorption are generally poorly tolerated because of unpalatability and associated gastrointestinal side effects. We suggest that there is now a viable alternative, colesevelam hydrochloride (WelChol, Sankyo Pharmaceuticals Inc., Japan).

A 30 year old man presented with steatorrhoea, progressive weight loss, marked abdominal bloating, and lethargy after a right hemicolectomy following a road traffic accident in 1966.

Physical examination, relevant blood tests, barium follow through, colonoscopy, and microscopic examination of colonic biopsies were normal. A trial of cholestyramine in preference to a SeCHAT scan caused cessation of diarrhoea on one sachet per day. However, his abdominal bloating continued unabated and he found the treatment unpalatable. Cholestyramine was therefore changed to colesevelam 2.5 g/3.75 g on alternate days. This was well tolerated, …
Ettriol Trinitrate and Prenylamine Lactate in Angina Pectoris
Authors: D. N. Phear
Journal: BMJ (1963)

MEDICALJOURNALwe have conducted a number of studies on the selenium content of teeth, placental tissue, and foetal cord blood, bovine milk, eggs, water, and human milk in relation to dental caries susceptibility in children.5-FThere is no doubt that the role played by trace elements in preventing dental caries requires further exploration.It is believed, however, that the study of trace elements that may be responsible for increasing the susceptibility to dental caries, such as selenium, should also be given serious consideration by research workers.-I am, etc.,
CD161 expression on hepatitis C virus-specific CD8+ T cells suggests a distinct pathway of T cell differentiation
Authors: John W. Northfield, Victoria Kasprowicz, Michaela Lucas, Nadine Kersting, Bertram Bengsh, Arthur Kim, Rodney E. Phillips, Bruce D. Walker, Robert Thimme, Georg Lauer, Paul Klenerman
Journal: Hepatology (2008)

Hepatitis C virus (HCV) causes chronic infection accompanied by a high risk of liver failure and hepatocellular carcinoma. CD8+ T cell responses are important in the control of viremia. However, the T cell response in chronic infection is weak both in absolute numbers and in the range of epitopes targeted. In order to explore the biology of this response further, we analyzed expression of a panel of natural killer cell markers in HCV compared with other virus-specific T cell populations as defined by major histocompatibility complex class I tetramers. We found that CD161 was significantly expressed on HCV-specific cells (median 16.8%) but not on CD8+ T cells specific for human immunodeficiency virus (3.3%), cytomegalovirus (3.4%), or influenza (3.4%). Expression was seen in acute, chronic, and resolved disease and was greatest on intrahepatic HCV-specific T cells (median 57.6%; P < 0.05). Expression of CD161 was also found on hepatitis B virus-specific CD8+ T cells. In general, CD161+CD8+ T cells were found to be CCR7- "effector memory" T cells that could produce proinflammatory cytokines (interferon-gamma and tumor necrosis factor-alpha) but contained scanty amounts of cytolytic molecules (granzyme B and perforin) and proliferated poorly in vitro. Expression of CD161 on CD8+ T cells was tightly linked to that of CXCR6, a chemokine with a major role in liver homing.We propose that expression of CD161 indicates a unique pattern of T cell differentiation that might help elucidate the mechanisms of HCV immunity and pathogenesis.
A conversation with Francis Collins
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2012)

We are joined by Francis Collins, a scientist who needs little introduction to the JCI audience. After getting his PhD in Physical Chemistry at Yale University and his medical degree at the University of North Carolina, Collins (Figure ​(Figure1)1) zeroed in on genetics as his area of concentration and is noted for his landmark discoveries of disease genes, and later his leadership of the Human Genome Project, which culminated in April 2003 with the completion of a finished sequence of the human genome. Since August 2009, Collins has served as the director of the NIH, the largest supporter of biomedical research in the world. The full interview can be seen on the JCI website, http://www.jci.org/kiosk/cgm.
Waiting times for scans to decrease, vows Department of Health
Authors: Allison Barrett
Journal: BMJ (2005)

Patients in England and Wales will have the option to change hospitals for quicker diagnostic scanning by the end of this year, the UK Department of Health has announced. Patients who wait for a long time for their first non-urgent diagnostic scan will be offered a different location for faster service. In November, patients with waiting times of more than 20 weeks for magnetic resonance imaging and computed tomography scans will have the option to move scanning locations. By April 2006, the offer will be extended to …
Genetic background of Brugada syndrome is more complex than what we would like it to be!
Authors: H. Abriel
Journal: Cardiovascular Research (2015)

This editorial refers to ‘Role of common and rare variants in SCN10A : results from the Brugada syndrome QRS locus gene discovery collaborative study’ by E.R. Behr et al ., doi:10.1093/cvr/cvv042. 

Everything must be taken into account. If the fact will not fit the theory—let the theory go. ―Agatha Christie, The Mysterious Affair at Styles 

Brugada syndrome (BrS) has been named after the description of the disease made by the Brugada brothers in 1992.1 BrS is clinically characterized by arrhythmic events, in particular ventricular fibrillation, resulting in syncope and sudden cardiac arrest mainly in middle-aged men. The ECG shows a peculiar down-sloping elevation of the ST segment in the right pre-cordial ECG leads with inversion of T-waves.2 Since 1998, a genetic component to BrS has been demonstrated.3 Over the past years, at least 20 genes have been proposed either to cause BrS or to be BrS-susceptibility genes.4

For several years, SCN5A , which encodes the ‘cardiac sodium channel’ Nav1.5, was presented as a gene ‘causing’ BrS in ∼20% of the patients; however, this concept had to be revised due to recent findings. First, in some families where the probands were found to carry SCN5A rare variants, other family members diagnosed with BrS did not carry the supposedly …
Uptake of cholesterol-rich remnant lipoproteins by human monocyte-derived macrophages is mediated by low density lipoprotein receptors.
Authors: C Koo, M E Wernette-Hammond, Z Garcia, M J Malloy, R Uauy, C East, D W Bilheimer, R W Mahley, T L Innerarity
Journal: Journal of Clinical Investigation (1988)

The uptake and degradation of cholesterol-rich remnant lipoproteins, referred to as beta-VLDL, are shown in the present study to be mediated by LDL receptors (apoB,E(LDL) receptors), not by unique beta-VLDL receptors. Human blood monocytes cultured for 5-7 d bound apoB- and/or apoE-containing lipoproteins from different species with affinities equivalent to those demonstrated for the receptors on cultured human fibroblasts. Low density lipoproteins competed effectively and completely with 125I-beta-VLDL for binding to and degradation by monocyte-derived macrophages. Specific polyclonal antibodies to bovine apoB,E(LDL) receptors abolished both LDL and beta-VLDL uptake by normal human monocyte-macrophages. Immunoblots of monocyte-macrophage extracts with these antibodies revealed a single protein in human macrophages with an apparent molecular weight identical to that of the apoB,E(LDL) receptor found on human fibroblasts. Like receptors on cultured human fibroblasts, the apoB,E(LDL) receptors on monocyte-macrophages responsible for 125I-beta-VLDL and 125I-LDL uptake were efficiently down regulated by preincubation of the cells with beta-VLDL or LDL. Finally, monocyte-macrophages from seven homozygous familial hypercholesterolemia subjects were unable to metabolize beta-VLDL or LDL, but demonstrated normal uptake of acetoacetylated LDL. The classic apoB,E(LDL) receptors on human monocyte-macrophages thus mediate the uptake of beta-VLDL by these cells.
Air Transportation After Eye Surgery-Reply
Authors: Willis A. Wingert
Journal: JAMA (1982)

In Reply.—  Dr Roper is correct in noting that the danger of air travel after recent eye surgery is expansion of gas bubbles remaining within the eye as the ambient pressure decreases. All such patients should be examined and cleared by an ophthalmologist before attempting to travel aboard pressurized or nonpressurized aircraft. Incidentally, this caution also applies to transportation by air ambulance services. The Commission on Emergency Medical Services' somewhat sweeping statement was made to ensure an ophthalmologist's clearance on every patient.
Methodologic frontiers in environmental epidemiology.
Authors: K J Rothman
Journal: Environmental Health Perspectives (1993)

Environmental epidemiology comprises the epidemiologic study of those environmental factors that are outside the immediate control of the individual. Exposures of interest to environmental epidemiologists include air pollution, water pollution, occupational exposure to physical and chemical agents, as well as psychosocial elements of environmental concern. The main methodologic problem in environmental epidemiology is exposure assessment, a problem that extends through all of epidemiologic research but looms as a towering obstacle in environmental epidemiology. One of the most promising developments in improving exposure assessment in environmental epidemiology is to find exposure biomarkers, which could serve as built-in dosimeters that reflect the biologic footprint left behind by environmental exposures. Beyond exposure assessment, epidemiologists studying environmental exposures face the difficulty of studying small effects that may be distorted by confounding that eludes easy control. This challenge may prompt reliance on new study designs, such as two-stage designs in which exposure and disease information are collected in the first stage, and covariate information is collected on a subset of subjects in state two. While the analytic methods already available for environmental epidemiology are powerful, analytic methods for ecologic studies need further development. This workshop outlines the range of methodologic issues that environmental epidemiologists must address so that their work meets the goals set by scientists and society at large.
Euthanasia
Authors: William W. Weddington
Journal: JAMA (1981)

EVEN though we think it to be a complication of modern technological medicine, euthanasia continues as an old issue for physicians and patients. Hippocrates and his associates addressed the concept in the fourth century BC,<sup>1</sup>long before the word "euthanasia" even arrived in the 17th century. Euthanasia means simply "a quiet and easy death." We use it now to indicate the deliberate death of a patient with a distressing and terminal disease.<sup>2</sup> Despite Hippocrates' injunction, a survey<sup>3</sup>of physicians practicing in two Seattle hospitals revealed that 87% of the respondents favored "negative" euthanasia (omission of lifepromoting therapies), and 80% indicated that they had used this in their practice. Fifteen percent of the physicians favored "positive" euthanasia; that is, they voted to legalize the use of death-promoting substances for certain patients. Hudson" points out that, although the last push for legalized active euthanasia peaked in the
PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome
Authors: Inga Ebermann, Jennifer B. Phillips, Max C. Liebau, Robert K. Koenekoop, Bernhard Schermer, Irma Lopez, Ellen Schäfer, Anne-Francoise Roux, Claudia Dafinger, Antje Bernd, Eberhart Zrenner, Mireille Claustres, Bernardo Blanco, Gudrun Nürnberg, Peter Nürnberg, Rebecca Ruland, Monte Westerfield, Thomas Benzing, Hanno J. Bolz
Journal: Journal of Clinical Investigation (2010)

Usher syndrome is a genetically heterogeneous recessive disease characterized by hearing loss and retinitis pigmentosa (RP). It frequently presents with unexplained, often intrafamilial, variability of the visual phenotype. Although 9 genes have been linked with Usher syndrome, many patients do not have mutations in any of these genes, suggesting that there are still unidentified genes involved in the syndrome. Here, we have determined that mutations in PDZ domain–containing 7 (PDZD7), which encodes a homolog of proteins mutated in Usher syndrome subtype 1C (USH1C) and USH2D, contribute to Usher syndrome. Mutations in PDZD7 were identified only in patients with mutations in other known Usher genes. In a set of sisters, each with a homozygous mutation in USH2A, a frame-shift mutation in PDZD7 was present in the sister with more severe RP and earlier disease onset. Further, heterozygous PDZD7 mutations were present in patients with truncating mutations in USH2A, G protein–coupled receptor 98 (GPR98; also known as USH2C), and an unidentified locus. We validated the human genotypes using zebrafish, and our findings were consistent with digenic inheritance of PDZD7 and GPR98, and with PDZD7 as a retinal disease modifier in patients with USH2A. Pdzd7 knockdown produced an Usher-like phenotype in zebrafish, exacerbated retinal cell death in combination with ush2a or gpr98, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium. Our data challenge the view of Usher syndrome as a traditional Mendelian disorder and support the reclassification of Usher syndrome as an oligogenic disease.
Acquired factor VIII inhibitor associated with lung abscess.
Authors: P S Ganly, J D Isaacs, M A Laffan, C Haslett, J M Hows
Journal: BMJ (1987)

typing was performed and the multiple antibiotic resistance confirmed by the Streptococcus Reference Laboratory, Colindale.Nose and throat swabs were obtained from all the immediate family-father, mother, a 3 year old brother, a 2 year old sister-and the index patient.The resistant strain was grown from the nose swabs ofthe index patient and the 3 year old sibling.A sensitive pneumococcus was grown from the nose of the 2 year old, whereas no pneumococci were grown from the parents.The neonate's infected eye was treated for three weeks with topical penicillin (lOx 106 U/l) with clinical and bacteriological cure.
Metabolism of cholesterol and low- and high-density lipoproteins in primary biliary cirrhosis: Cholesterol absorption and synthesis related to lipoprotein levels and their kinetics
Authors: Helena Gylling, Martti Färkkilä, Matti Vuoristo, Tatu A. Miettinen
Journal: Hepatology (1995)

Cholesterol absorption, elimination, and synthesis, and low-density lipoprotein (LDL) and high density lipoprotein (HDL) kinetics were studied in patients with mild to severe primary biliary cirrhosis (PBC) (n = 16) to show how this cholestatic disease modified cholesterol and lipoprotein metabolism as compared with healthy controls (n = 50). Serum total and lipoprotein cholesterol and triglyceride levels were similar in the two groups, but in PBC, especially in severe forms, very low density lipoprotein (VLDL) was rich in apoprotein (apo) B and cholesterol and low in triglycerides, whereas LDL was rich in triglycerides and low in esterified cholesterol, and HDL was enriched by surface lipids, phospholipids, and free cholesterol. In severe PBC, the fractional catabolic rate (FCR) for LDL apo B was reduced. The transport rate (TR) for LDL apo B was unaffected and it tended to correlate with the LDL apo B and LDL cholesterol levels in PBC, whereas in the controls the LDL apo B concentration was regulated by both the FCR and TR, and LDL cholesterol was regulated only by FCR. FCR for apo A-I in HDL was unaltered in PBC, but TR for apo A-I was reduced in the severe cases. Cholesterol absorption efficiency was significantly reduced in PBC (14.5 +/- 3.0% in severe PBC and 34.0 +/- 2.5% in mild PBC vs. 47.4 +/- 1.4% in the controls, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
SKTN REACTIONS TO 9-BROMOFLUORENE
Authors: E. W. POWELL
Journal: British Journal of Dermatology (1968)

SUMMARY. A man aged 22, exposed to 9‐bromofluorene developed an extensive bullous eruption. A patch test with pure 9‐bromofluorene in a healthy subject not previously exposed to this substance provoked a mild and transient reaction at 24 hr., but a severe reaction 9–10 days later. The delayed reaction was characterized histologically by intense epidermal hyperplasia, pseudoepitheliomatous in degree, and a dense cellular infiltrate in the upper dermis. These effects are discussed in relation to the reactions normally obtained in contact hypersensitivity.
Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation
Authors: A C Lankester, M B Bierings, E R van Wering, A J M Wijkhuijs, R A de Weger, J T Wijnen, J M Vossen, B Versluys, R M Egeler, M J D van Tol, H Putter, T Révész, J J M van Dongen, V H J van der Velden, M W Schilham
Journal: Leukemia (2010)
[517] ETV RE-TREATMENT OF NUCLEOSIDE-NAIVE HBeAg(−) PATIENTS
Authors: H. Senturk, Y. Lurie, A. Gadano, C.K. Tan, T. Tran, S.D. Lee, N. Tsai, H. Cheinquer, J. Yang, R. Tamez, R. Hindes
Journal: Journal of Hepatology (2007)
A third tal-1 promoter is specifically used in human T cell leukemias.
Authors: O Bernard, O Azogui, N Lecointe, F Mugneret, R Berger, C J Larsen, D Mathieu-Mahul
Journal: The Journal of Experimental Medicine (1992)

A common feature of T cell acute lymphoblastic leukemias (T-ALLs) is the presence of structural alteration of the 5' part of the tal-1 locus, localized on chromosomal band 1p32. These alterations consist of either a t(1;14)(p32;q11) chromosomal translocation (3% of T-ALLs) or tald submicroscopic deletion (12-25% additional T-ALLs). We have characterized a case of T-ALL with t(1;14)(p32;q11) in which, unlike the majority of t(1;14), the recombination with the T cell receptor delta elements affected the 3' side of the tal-1 locus. In this case, tal-1 transcription is initiated from a promoter located within the fourth exon similarly to the DU 528 cell line. In a T-ALL bearing a t(1;14) affecting the 5' part of tal-1, two types of tal-1 transcripts were observed, namely those probably initiated from the D delta region juxtaposed to tal-1 by the translocation, and those from the exon 4 promoter. It is interesting that this exon 4 promotion was also found in leukemic T cell lines and T-ALL samples without apparent tal-1 genomic alteration. In contrast, no transcript initiated from the exon 4 promoter was found in T-ALL with tald1 or tald2 deletion. In these cells, tal-1 is expressed via SIL-tal-1 fused transcripts. Finally, this exon 4 initiation was detected neither in normal bone marrow, nor in malignant cells from the erythroid/megakaryocytic lineages. Taken as a whole, these data suggest that the exon 4 promoter is specifically active in T cell lineage.
India has a problem with palm oil
Authors: B. Shankar, C. Hawkes
Journal: BMJ (2013)

The existence of heterogeneous populations of dorsal root ganglion (DRG) neurons conveying different somatosensory information is the basis for the perception of touch, temperature, and pain. A differential expression of transient receptor potential (TRP) cation channels contributes to this functional heterogeneity. However, little is known about the development of functionally diverse neuronal subpopulations. Here, we use calcium imaging of acutely dissociated mouse sensory neurons and quantitative reverse transcription PCR to show that TRP cation channels emerge in waves, with the diversification of functional groups starting at embryonic day 12.5 (E12.5) and extending well into the postnatal life. Functional responses of voltage-gated calcium channels were present in DRG neurons at E11.5 and reached adult levels by E14.5. Responses to capsaicin, menthol, and cinnamaldehyde were first seen at E12.5, E16.5, and postnatal day 0 (P0), when the mRNA for TRP cation channel, subfamily V, member 1 (TRPV1), TRP cation channel, subfamily M, member 8 (TRPM8), and TRP cation channel, subfamily A, member 1 (TRPA1), respectively, was first detected. Cold-sensitive neurons were present before the expression or functional responses of TRPM8 or TRPA1. Our data support a lineage relationship in which TRPM8- and TRPA1-expressing sensory neurons derive from the population of TRPV1-expressing neurons. The TRPA1 subpopulation of neurons emerges independently in two distinct classes of nociceptors: around birth in the peptidergic population and after P14 in the nonpeptidergic class. This indicates that neurons with similar receptive properties can be generated in different sublineages at different developmental stages. This study describes for the first time the emergence of functional subtypes of sensory neurons, providing new insight into the development of nociception and thermoreception.