tbuckley/cabot-search huggingface dataset:
Tuberculosis: who should prescribe?
Authors: F J Woodroffe
Journal: BMJ (1982)

these methods depend at present on electric power to drive centrifuges.The MAEC method has been adapted, not only for rural hospitals but also for field-survey use by the production of complete "kits" of the equipment and materials needed, and has been widely used for field surveys in the Ivory Coast and Uganda, using a small petrol-driven
THE EMPLOYMENT OF CARMIN IN GASTRO-INTESTINAL DIAGNOSIS
Authors: SEYMOUR BASCH
Journal: JAMA (1913)

and shows on section edema of the substance and congestion; púnete cruenta show marked spreading, ' .I he basal ganglia are quite dark in color, as is also the cerebellum, and blood flows on section of vessels of any size.The floors of the lateral ventricles and fourth ventricle show granular ependymitis.Pons and medulla normal.Spinal cord normal at cervical segment.Thyroid, adrenals and pituitary: These all show intense congestion.Anatomic Diagnosis.-Edemaand congestion of lungs; small infarct, right lower lobe; acute gastritis; edema and conges- tion of brain; acute congestion of all parenchyinntous organs and ductless glands.Cause of death: Acute arsenic poisoning.
Molecular analysis of human gamma/delta+ clones from thymus and peripheral blood.
Authors: G Casorati, G De Libero, A Lanzavecchia, N Migone
Journal: The Journal of Experimental Medicine (1989)

We analyzed the V gamma and V delta gene usage in TCR-gamma/delta-bearing T cell clones isolated from human peripheral blood and postnatal thymus using V-specific mAbs and Southern and Northern analyses. In peripheral blood most of the gamma/delta cells express the V gamma 9-JP-C gamma 1 chain paired with a delta chain bearing the V delta 2 gene product. This heterodimer is very rare in the postnatal thymus, where a different and less restricted pairing of V gamma 9 and V delta 2 chains is found. These findings indicate that physical constraints cannot explain the overrepresentation of a particular V gamma 9-JP/V delta 2 heterodimer in the peripheral blood, and we discuss alternative mechanisms that may account for this differential distribution. In addition, this analysis allowed us to map the specificity of the delta TCS1 mAb to V delta 1-J delta 1 and to identify at least five different expressed V delta genes.
Synergism between Etoposide and 17-AAG in Leukemia Cells: Critical Roles for Hsp90, FLT3, Topoisomerase II, Chk1, and Rad51
Authors: Qing Yao, Brenda Weigel, John Kersey
Journal: Clinical Cancer Research (2007)

Abstract Purpose: DNA-damaging agents, such as etoposide, while clinically useful in leukemia therapy, are limited by DNA repair pathways that are not well understood. 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG), an inhibitor of the molecular chaperone heat shock protein 90 (Hsp90), inhibits growth and induces apoptosis in FLT3+ leukemia cells. In this study, we evaluated the effects of etoposide and 17-AAG in leukemia cells and the roles of Hsp90, FMS-like tyrosine kinase 3 (FLT3), checkpoint kinase 1 (Chk1), Rad51, and topoisomerase II in this inhibition. Experimental Design: The single and combined effects of 17-AAG and etoposide and the mechanism of these effects were evaluated. FLT3 and the DNA repair-related proteins, Chk1 and Rad51, were studied in small interfering RNA (siRNA)–induced cell growth inhibition experiments in human leukemia cells with wild-type or mutated FLT3. Results: We found that etoposide and the Hsp90/FLT3 inhibitor 17-AAG, had synergistic inhibitory effects on FLT3+ MLL-fusion gene leukemia cells. Cells with an internal tandem duplication (ITD) FLT3 (Molm13 and MV4;11) were more sensitive to etoposide/17-AAG than leukemias with wild-type FLT3 (HPB-Null and RS4;11). A critical role for FLT3 was shown in experiments with FLT3 ligand and siRNA targeted to FLT3. An important role for topoisomerase II and the DNA repair-related proteins, Chk1 and Rad51, in the synergistic effects was suggested from the results. Conclusions: The repair of potentially lethal DNA damage by etoposide in leukemia cells is dependent on intact and functioning FLT3 especially leukemias with ITD-FLT3. These data suggest a rational therapeutic strategy for FLT3+ leukemias that combines etoposide or other DNA-damaging agents with Hsp90/FLT3 inhibitors such as 17-AAG.
THE ENCEPHALITIS PROBLEM
Authors: JOSEPHINE B. NEAL
Journal: JAMA (1934)

The encephalitis problem has many angles. It is easy enough to call attention to the points involved but practically impossible to present any satisfactory answers.  For nearly twenty years there have been outbreaks in various parts of the world of acute infections of the central nervous system, exclusive of poliomyelitis and meningitis. These have differed in seasonal incidence, in age distribution, in case fatality and in clinical manifestations. They have usually been described as some form of acute encephalitis or encephalomyelitis. In conjunction with these more or less spontaneous cases there has been a marked increase in the reports of encephalitis following vaccination, measles and other acute infections. While it is now known that encephalitis may run a mild course in the acute stage and escape recognition, the symptoms in the more severe cases are so arresting that they could hardly have passed unnoticed. It is not probable that clinical
Psychiatry and the Mysterious Medical Complaint
Authors: Donald W. Goodwin
Journal: JAMA (1969)

When patients complain of pain or some other physical symptom, and no physical cause can be found, it is not enough to suggest that the symptom is functional or psychological. The physician should rule out three psychiatric disorders in which unexplained physical symptoms often dominate the clinical picture. These are hysteria, anxiety neurosis, and depression. Each is a definite syndrome with specific diagnostic criteria and a well-documented natural history. Hysteria and anxiety neurosis often can be managed as successfully by an internist or general practitioner as by a psychiatrist. Depression more often justifies a psychiatric referral. "Functional" symptoms which cannot be attributed to one of these syndromes often warrant further search for an organic cause.
Temporal Trends in Phthalate Exposures: Findings from the National Health and Nutrition Examination Survey, 2001–2010
Authors: Ami R. Zota, Antonia M. Calafat, Tracey J. Woodruff
Journal: Environmental Health Perspectives (2014)

Background: Phthalates are ubiquitous environmental contaminants. Because of potential adverse effects on human health, butylbenzyl phthalate [BBzP; metabolite, monobenzyl phthalate (MBzP)], di-n-butyl phthalate [DnBP; metabolite, mono-n-butyl phthalate (MnBP)], and di(2-ethylhexyl) phthalate (DEHP) are being replaced by substitutes including other phthalates; however, little is known about consequent trends in population-level exposures.Objective: We examined temporal trends in urinary concentrations of phthalate metabolites in the general U.S. population and whether trends vary by sociodemographic characteristics.Methods: We combined data on 11 phthalate metabolites for 11,071 participants from five cycles of the National Health and Nutrition Examination Survey (2001–2010). Percent changes and least square geometric means (LSGMs) were calculated from multivariate regression models.Results: LSGM concentrations of monoethyl phthalate, MnBP, MBzP, and ΣDEHP metabolites decreased between 2001–2002 and 2009–2010 [percent change (95% CI): –42% (–49, –34); –17% (–23, –9); –32% (–39, –23) and –37% (–46, –26), respectively]. In contrast, LSGM concentrations of monoisobutyl phthalate, mono(3-carboxypropyl) phthalate (MCPP), monocarboxyoctyl phthalate, and monocarboxynonyl phthalate (MCNP) increased over the study period [percent change (95% CI): 206% (178, 236); 25% (8, 45); 149% (102, 207); and 15% (1, 30), respectively]. Trends varied by subpopulations for certain phthalates. For example, LSGM concentrations of ΣDEHP metabolites, MCPP, and MCNP were higher in children than adults, but the gap between groups narrowed over time (pinteraction &lt; 0.01).Conclusions: Exposure of the U.S. population to phthalates has changed in the last decade. Data gaps make it difficult to explain trends, but legislative activity and advocacy campaigns by nongovernmental organizations may play a role in changing trends.Citation: Zota AZ, Calafat AM, Woodruff TJ. 2014. Temporal trends in phthalate exposures: findings from the National Health and Nutrition Examination Survey, 2001–2010. Environ Health Perspect 122:235–241; http://dx.doi.org/10.1289/ehp.1306681
Dorsal Dimelia of the Fourth Toe in a Patient With Incontinentia Pigmenti
Authors: Marc Z. Handler, Jasem Alshaiji, Sadegh Amini, Jan Izakovic
Journal: JAMA Dermatology (2013)

Development of a second nail plate on either the plantar or palmar surface of a digit, known as a double nail, is an extremely rare malformation. When dorsalization of the plantar skin is also present, the condition is referred to as dorsal dimelia. Additional findings associated with dorsal dimelia may include loss of flexion creases with absent flexion at the interphalangeal joints and tapering of the distal phalanx seen on radiography. We report herein a case of an affected toe in a patient with incontinentia pigmenti (IP).
807. Addition of HU to GCV Induces Bystander Cytotoxicity in Co-Cultures of HSVTK-Expressing and Non-Expressing HeLa Cells
Authors: Brian G. Gentry, Paul D. Boucher, Donna S. Shewach
Journal: Molecular Therapy (2005)

Expression of the herpes simplex virus type I thymidine kinase (HSVTK) gene in tumor cells sensitizes them to the antiviral agent ganciclovir (GCV). Incubation with GCV results not only in cytotoxicity from cells that express the transgene, but neighboring bystander cells as well. Bystander cytotoxicity has been attributed to the transfer of phosphorylated GCV metabolites from HSVTK-expressing to non-expressing cells through protein channels known as gap junctions. We have previously reported good bystander cytotoxicity in the U251 glioblastoma and SW620 colon carcinoma cell lines, which have 84% and 39% gap junction intercellular communication (GJIC), respectively. However, in the HeLa cell line (23% GJIC), no bystander cytotoxicity resulted from incubating a co-culture of HSVTK-expressing and bystander HeLa cells with GCV. Further analysis revealed that lack of bystander cytotoxicity in these cells was not due to an inability to transfer phosphorylated GCV, but resulted from a low level of transfer along with a rapid half-life of GCVTP in bystander cells (3.1 hrs) when compared to the HSVTK-expressing cells (12.3 hrs). We hypothesized that reduction of the endogenous competitor for GCVTP incorporation into DNA, dGTP, would increase levels of GCV incorporation into DNA resulting in the induction of bystander cytotoxicity. To that end, the effect of hydroxyurea (HU), a ribonucleotide reductase inhibitor, on GCV cytotoxicity in cultures of 100% HSVTK-expressing HeLa cells and co-cultures of HSVTK-expressing and bystander HeLa cells was examined. Isobologram analysis of the interaction between GCV and HU demonstrated an additive-antagonistic effect on 100% cultures of HSVTK-expressing HeLa cells, while exhibiting a synergistic effect on the HSVTK-expressing and bystander cells in a co-culture. To determine the mechanism for the synergistic cytotoxicity demonstrated in each of the populations from the co-culture when incubated with GCV and HU, GCVTP and dNTP pools were quantified and the results were compared to 100% cultures of HSVTK-expressing HeLa cells. The results demonstrated a significant increase in the GCVTP:dGTP values in cultures of 100% HSVTK-expressing cells (>2.5 fold) and in co-cultures of HSVTK-expressing cells (>1.4 fold) and bystander cells (>1.8 fold) at 4 hours. However, at 12 hours the GCVTP:dGTP value for 100% cultures of HSVTK-expressing HeLa cells was at control levels (1.3 0.5 fold) while the values for HSVTK-expressing cells (>2.7 fold) and bystander cells (>4.9 fold) in co-culture were still significantly higher. These data suggest that the prolonged increase in the GCVTP:dGTP value in co-cultures incubated with GCV and HU leads to an increase in the levels of GCVTP incorporated into DNA resulting in synergistic cytotoxicity.
Advantages of a Perineal Curve Applied to Midwifery Forceps
Authors: W. Radcliffe
Journal: BMJ (1953)

MEDICAL MEMORANDA specimens appeared normal in colour.Cortisone, 100 mg., was again given intramuscularly.This was followed by a dose of 50 mg.on August 28 and 29.On the 30th he was sitting up; the conjunctivae were icteric, and there was slight oedema of the feet and face.No further cortisone was given.The urinary output on August 28, 29, and 30 was about 20 oz.(570 ml.) a day, and some urine was voided into the bed; it contained no methaemoglobin.The anaemia was treated with iron, and the malaria from the outset with mepacrine.The child made an uneventful recovery and was discharged.COMMENT It is suspected that blackwater fever is a haemolytic disease occurring in those infected with P. falciparum and whose cells have been sensitized by quinine.As cortisone lowers the sensitivity of body tissues in certain allergic states (Carey et al., 1950), it was given in the hope that it might reduce the sensitivity of the cells to the circulating haemo- lysin and relieve the renal corfical ischaemia responsible for the anuria.Although the clinical state of cases of blackwater fever is known to alter rapidly, it was felt that the condition of this child on the second day was such that a fatal outcome was inevitable.Cortisone seemed to have had an effect in this case.
QS- and QR-Pattern in Leads V <sub>3</sub> and V <sub>4</sub> in Absence of Myocardial Infarction: Electrocardiographic and Vectorcardiographic Study
Authors: BORYS SURAWICZ, ROBERT G. VAN HORNE, JOHN R. URBACH, SAMUEL BELLET
Journal: Circulation (1955)

A QS or QR pattern in the absence of myocardial infarction is frequently present in lead V 3 and occasionally in lead V 4 . Exploration by means of multiple chest and abdominal unipolar leads and vectorcardiograms revealed that in almost all such cases, the vector of the initial portions of the QRS complex is directed downwards. Accordingly, in the absence of infarction, patients presenting this pattern almost invariably showed an initial R wave in the leads recorded from positions below the standard level of V 3 and V 4 . The vast majority of patients with myocardial infarction with a similar QRS pattern showed a Q wave in the lower leads. Consideration of vertical components of cardiac voltages may be helpful in the interpretation of the precordial leads.
INITIAL EXPERIENCE OF THE NOVEL MOBILE TELEMEDICINE SYSTEM IN REAL-TIME TRANSMISSION OF PREHOSPITAL 12-LEAD ECG FOR CARDIAC EMERGENCY
Authors: Nobuhito Yagi, Yoritaka Otsuka, Yukiko Oe, Takafumi Yamane, Futoshi Yamanaka, Eiji Tada, Yoichiro Kasahara, Yu Kataoka, Hiroyuki Yokoyama, Hiroshi Nonogi
Journal: Journal of the American College of Cardiology (2010)
1050 Hepcidin expression is down-regulated in alcohol-fed rats: a possible pathogenic factor in alcohol related hepatic siderosis
Authors: T CHEUNG, L FLETCHER, K BRIDLE, T MURPHY, D CRAWFORD
Journal: Hepatology (2003)

IntroductionBoth alcohol and excess iron in the liver can induce tissue damage and lead to fibrosis and ultimately cirrhosis. Hepatic siderosis is often seen in patients with alcoholic liver disease. The pathogenic mechanisms underlying this phenomenon have not been well characterized. Hepcidin, a recently discovered liver-derived circulating peptide, has been implicated in the homeostasis of iron metabolism and in the regulation of iron absorption. Hepcidin is believed to be a negative regulator of intestinal iron absorption. Divalent metal transporter 1 (DMT1) and iron-regulated protein (IREG1) are the major iron transporters in duodenal enterocytes, with DMT1 responsible for apical uptake and IREG1 for basolateral export of iron. The effect of alcohol on the expression of hepcidin, DMT1 and IREG1 is not known.ConclusionHepcidin expression is significantly decreased in the alcohol-fed rats. Altered hepcidin expression may be an important contributing factor to hepatic siderosis often seen in human alcoholic liver disease.
Informed Consent: II
Authors: Leslie J. Miller
Journal: JAMA (1980)

IN THE preceding article (244:2100-2103, 1980), the nature of the doctrine of informed consent and various issues relating to the elements of a cause of action based on lack of informed consent were discussed. This article discusses various defenses to informed consent claims. <h3>DEFENSES TO INFORMED CONSENT CLAIMS</h3> There are a number of defenses to a claim of lack of informed consent. Some of these relate to the lack of materiality of the risk that was allegedly not disclosed. Others relate to standards of medical practice or to the question of proximate cause of the patient's injury. The major defenses have all been listed in a large number of cases and appear to be recognized in a large majority of jurisdictions. Unfortunately, however, the scope of the various defenses is extremely unclear, for two reasons. First, the applicability of such defenses depends primarily on the facts of the particular case. It
357. Site-Specific Integration of Immortalization Genes in Human Adult Stem Cells Mediated by DirectIt™ Recombinases
Authors: Anna Tretiakova, Malla Padidam
Journal: Molecular Therapy (2006)

Expansion of human adult stem cells is hampered by the senescence of the cells. The limited proliferative capacity of human primary cells hinders in vitro studies of growth and differentiation and limits their ability to be genetically modified for cell therapy and tissue engineering applications. Immortalized cells have been successfully produced by transfecting with human telomerase reverse transcriptase (hTERT), SV40 large T antigen (T-Ag), v-Myc, papillomavirus E6 and E7, adenovirus E1A, and other genes. Previous studies have indicated that hTERT-immortalized cells have fewer karyotypic changes and show features of normal differentiation. However, the current methods of gene insertion in adult stem cells cannot target insertion of transgenes to predetermined locations in chromosomes, thus posing several potential problems including: inappropriate levels or timing of therapeutic gene expression, inactivation of an essential endogenous gene, or activation of an oncogene. Targeting the gene to known locations in the genome is needed for the advancement of safe and effective therapies. We used two DirectIt™ recombinases for insertion of hTERT, T-Ag, or v- Myc genes to endogenous sites in human mesenchymal stem cells (MSCs), neural stem cells (NSCs), and retinal pigment epithelium cells (RPE). DirectIt™ recombinases are phage integrases that are functional in mammalian cells and catalyze highly efficient unidirectional recombination between short heterologous target sites resulting in integration or deletion of DNA depending on the orientation and location of target sites. In addition, they are efficient at integrating DNA at endogenous pseudo target sequences in human chromosomes. Human MSCs, NSCs and RPE with stably integrated hTERT or T-Ag were selected and expanded. Expanded cultures had telomerase and T-Ag as detected on a western blot and also expressed GFP gene that was included in the plasmid construct . MSCs with stably integrated hTERT or T-Ag have now undergone more than 40 population doublings and continue to proliferate. Identification of genomic integration sites in cells that continue to proliferate is in progress. Identification of the genomic locations that support long term expression of transgene would facilitate future isolation of clones with integrations at that location. These results suggest that DirectIt™ recombinases can be used for precise integration of genes at known genomic locations for research and therapeutic applications.
A Case of Renal Moniliasis
Authors: J. F. E. Gillam, D. H. Wadelton
Journal: BMJ (1958)

A Case of Renal MoniiasisRecent literature indicates that the successful use of anti- biotics against bacterial infections may provide conditions in which the normal commensals, particularly yeasts, become dangerously pathogenic.Whether this is due to direct stimulation or to the eradication of competitors for sustenance is doubtful, but cases have been described of septicaemia with candida in metastatic abscesses in the brain and renal cortex and of fatal pulmonary moniliasis.All of these followed antibiotic treatment for bacterial infections.
Coronary bypass surgery should not be offered to smokers.
Authors: M J Underwood, J S Bailey
Journal: BMJ (1993)

Controversies in TreatmentShould smokers be offered coronary bypass surgery?Wihen resources are restricted and some form of rationing of health care is effectively taking place is it ethical to restrict the access ofpatients to particular treatments if there are alterable factors in their lifestyle which make the treatment less likely to work?Mr 3'ohn Bailey, cardiothoracic surgeon, and Dr Matthew Shiu, general practitioner, have disagreed in a television debate on whether smokers should be given the same opportunity for coronary artery bypass graft surgery as non-smokers- or any opportunity at all.We invited them to put their differing views, and then invited a surgeon from another discipline and another generalpractitioner, both interested in medical ethics, to comment.Coronary bypass surgery should not be offered to smokers M J Underwood, J S Bailey Cigarette smoking accelerates the progression of coronary artery disease' 2 and is a determinant of early death in patients awaiting coronary bypass surgery.3Optimal surgical treatment results in substantial reduction of symptoms with increased exercise tolerance, freedom from angina, and in certain subgroups prolonged survival.46Autogenous saphenous vein continues to be widely used as a conduit for coronary revascularisation.' Unfortunately, coronary vein graft disease is a major cause of mortality and morbidity and is responsible for recurrent angina, myocardial infarction, and compro- mised ventricular function.8One in 10 vein grafts undergo thrombotic occlusion within two weeks of operation,9 and diffuse intimal hyperplasia is a common finding after one year.9By five years, frank atherosclerotic lesions are identifiable in many grafts.'0Early patency rates may be improved with anti- platelet agents such as aspirin and dipyridamole" but this protective effect is greatly reduced in patients who continue to smoke,'2 presumably as a result of increased thrombogenicity'3-16 and enhanced platelet reactivity,'7 which is well recognised in smokers.Late thrombotic occlusion is also considerably increased in patients who continue to smoke after surgery,'8 and