tbuckley/cabot-search huggingface dataset:
A flexible model for planning facilities for patients with end-stage renal failure.
Authors: I T Wood, N P Mallick, B Moores
Journal: BMJ (1980)

Resource needs for patients with renal failure change as policies vary and survival improves. Thus a model was developed to estimate the facilities (number of beds) needed for such patients in the North-west Region; national resource needs could be obtained by multiplying the regional needs by eleven. The model predicted an unforeseen demand for hospital and satellite unit facilities and for unit back-up beds. The increasing survival of transplants is an important determinant of resource needs, and the model readily indicates the impact of changes in this factor.
Syphilis Control — A Continuing Challenge
Authors: Edward W. Hook, Rosanna W. Peeling
Journal: New England Journal of Medicine (2004)

Syphilis. The name of this widespread and ancient disease is familiar to health care providers worldwide. This name recognition, however, belies the complexity of the disease, as well as the diagnostic and therapeutic challenges that continue to affect global efforts to control syphilis. Early (primary or secondary) syphilis is typically marked by ulcerative lesions that occur initially at the site of inoculation, followed several months later by widespread cutaneous, mucosal, and even systemic manifestations of the dissemination of the causal agent, Treponema pallidum (see Figure 1). Even without treatment, both primary and secondary lesions resolve, and the infection enters a “latent” . . .
THE PRECIPITIN REACTION OF THYROGLOBULIN
Authors: LUDVIG HEKTOEN
Journal: JAMA (1923)

Thyroglobulin, first isolated by Oswald, is a comparatively constant compound in different species, except, of course, for variations in the iodin content. So far as we can learn, the antigenic properties of thyroglobulin have not been studied, and it occurred to us that it would be of interest to study them. Accordingly, we prepared thyroglobulin from beef, swine, and human thyroids in the usual way, but with special efforts to obtain as pure a product as possible.  The thyroids were freed from fat and connective tissue and torn into small pieces, which were washed in water until almost white, and then extracted in the icebox with salt solution containing a little thymol. After being filtered through paper several times, the extract was precipitated with an equal quantity of concentrated ammonium sulphate solution, and the precipitate was washed with a 50 per cent. ammonium sulphate solution, dissolved in salt solution, and
DIETETIC TREATMENT OF DIABETES.
Authors: N. S. DAVIS
Journal: JAMA (1900)

While something can be done for diabetics by medicinal treatment, reliance must be chiefly placed on a regulated diet. The principle of diabetic diet is well understood and does not need recapitulation here. There are some details of the management of diet which are not as generally regarded as they should be and which are quite essential to successful treatment. For convenience in discussing the diet of diabetes, cases can be grouped under three heads, first the mildest, second the moderate, third the severe cases. Acute cases, which are seen almost exclusively in childhood and early adult life, belong to the last group, as do some of those chronic from the start. Mild cases may gradually grow more severe. Not unfrequently a case is from its inception of moderate or severe type. Those cases which can be called the mildest will cease to eliminate sugar in the urine when the
Incidental Vesicocolic Fistula on Routine Bone Scintigraphy
Authors: Myung-Hee Sohn, Seok Tae Lim, Young Jin Jeong, Dong Wook Kim, Hwan-Jeong Jeong, Chang-Yeol Yim
Journal: Clinical Nuclear Medicine (2010)

An unexpected vesicocolic fistula can be detected incidentally on routine bone scintigraphy. A 55-year-old man who had a radical colectomy for carcinoma of the sigmoid colon 1 year previously underwent bone scintigraphy to evaluate bone metastasis. Whole-body images showed an abnormal accumulation of radioactivity in the right lower quadrant of the abdomen, but the radioactivity did not precisely define a structure. Additional delayed images obtained after 15 and 24 hours of the initial image localized a vesicocolic fistula. Subsequent radionuclide cystography confirmed leakage of the radioactivity from the bladder.
Prescription of oxygen concentrators for long term oxygen treatment
Authors: J P Dilworth, R J White, C M B Higgs, P A Jones
Journal: BMJ (1988)

apart; forced expiratory volume in one second <1 5 1; and forced vital capacity <2 1).Two other patients had stable hypoxia shown on one occasion and a forced expiratory volume in one second of <1 5 1.A further two had only stable hypoxia documented on one occasion and no results from spirometry.Five patients were recommended concentrators without evidence of stable hypoxia: three had an arterial oxygen pressure >7 3 kPa and no values were documented in the two others.Six
The Role of 17β-Hydroxysteroid Dehydrogenases in Modulating the Activity of 2-Methoxyestradiol in Breast Cancer Cells
Authors: Simon P. Newman, Christopher R. Ireson, Helena J. Tutill, Joanna M. Day, Michael F.C. Parsons, Mathew P. Leese, Barry V.L. Potter, Michael J. Reed, Atul Purohit
Journal: Cancer Research (2006)

Abstract The bis-sulfamoylated derivative of 2-methoxyestradiol (2-MeOE2), 2-methoxyestradiol-3,17-O,O-bis-sulfamate (2-MeOE2bisMATE), has shown potent antiproliferative and antiangiogenic activity in vitro and inhibits tumor growth in vivo. 2-MeOE2bisMATE is bioavailable, in contrast to 2-MeOE2 that has poor bioavailability. In this study, we have examined the role of 17β-hydroxysteroid dehydrogenase (17β-HSD) type 2 in the metabolism of 2-MeOE2. In MDA-MB-231 cells, which express high levels of 17β-HSD type 2, and in MCF-7 cells transfected with 17β-HSD type 2, high-performance liquid chromatography analysis showed that a significant proportion of 2-MeOE2 was metabolized to inactive 2-methoxyestrone. Furthermore, MCF-7 cells transfected with 17β-HSD type 2 were protected from the cytotoxic effects of 2-MeOE2. In contrast, no significant metabolism of 2-MeOE2bisMATE was detected in transfected cells and 17β-HSD type 2 transfection did not offer protection against 2-MeOE2bisMATE cytotoxicity. This study may go some way to explaining the poor bioavailability of 2-MeOE2, as the gastrointestinal mucosa expresses high levels of 17β-HSD type 2. In addition, this study shows the value of synthesizing sulfamoylated derivatives of 2-MeOE2 with C17-position modifications as these compounds have improved bioavailability and potency both in vitro and in vivo. (Cancer Res 2006; 66(1): 324-30)
Unlinked data sources underestimate risk of cardiovascular disease
Authors: R. J. Stevens, R. McManus
Journal: BMJ (2013)

<h3>Abstract</h3> Here we describe the first worldwide haplotype map for soybean (GmHapMap) constructed using whole-genome sequence data for 1,007 <i>Glycine max</i> accessions and yielding 15 million variants. The number of unique haplotypes plateaued within this collection (4.3 million tag SNPs) suggesting extensive coverage of diversity within the cultivated germplasm. We imputed GmHapMap variants onto 21,618 previously genotyped (50K array/210K GBS) accessions with up to 96% success for common alleles. A GWAS performed with imputed data enabled us to identify a causal SNP residing in the <i>NPC1</i> gene and to demonstrate its role in controlling seed oil content. We identified 405,101 haplotypes for the 55,589 genes and show that such haplotypes can help define alleles. Finally, we predicted 18,031 putative loss-of-function (LOF) mutations in 10,662 genes and illustrate how such a resource can be used to explore gene function. The GmHapMap provides a unique worldwide resource for soybean genomics and breeding.
A CASE OF PSEUDOHERMAPHRODITISM
Authors: Rita S. Finkler
Journal: JAMA (1934)

Pseudohermaphroditism has always been a subject of fascination and interest to the urologist, gynecologist and general practitioner. Unusual cases of true hermaphroditism and pseudohermaphroditism have been brought to the attention of the medical profession from time to time. I here present another case, which is of much interest from its clinical, endocrinologic and psychologic aspects. The patient, brought up as a girl, was first seen by me casually, five years ago, while I was attending another member of the family. At that time she was 13½ years old. She was short and stocky, was very timid, and had a deep masculine voice, a square masculine chest without any signs of breast development, and a masculine distribution of hair on the body and extremities. She was not menstruating yet. I saw the girl again a year later. Her mother called my attention to the fact that her menstrual periods were not
Newly Acquired Left Bundle-Branch Block: The Framingham Study
Authors: JOHN F. SCHNEIDER
Journal: Annals of Internal Medicine (1979)

Cardiovascular abnormalities were identified prospectively in all 70 persons who developed complete right bundle-branch block (RBBB) in The Framingham Study during 18 years of biennial follow-up. Most were hypertensive before the appearance of RBBB. Although the initial appearance of RBBB was usually unaccompanied by overt clinical events, the subsequent incidence of coronary disease and congestive failure was two and one-half and four times greater, respectively, than that in matched control subjects without RBBB. The incidence of cardiovascular disease mortality was almost three times greater in persons who developed RBBB than in an age-matched sample of the population-at-large. This excess of cardiovascular disease mortality was related primarily to the high prevalence of associated cardiovascular abnormalities. Only 21% remained free from clinically apparent cardiovascular abnormalities. A QRS duration of greater than or equal to 130 ms and a QRS axis between -45 degrees and -90 degrees identified those most likely to have associated cardiovascular abnormalities.
Mithramycin blocks protein binding and function of the SV40 early promoter.
Authors: R Ray, R C Snyder, S Thomas, C A Koller, D M Miller
Journal: Journal of Clinical Investigation (1989)

Specific interactions between DNA and transcription factors are necessary for transcription initiation. These interactions provide a potential target for the selective inhibition of eukaryotic gene expression. Mithramycin is a DNA binding antibiotic which, in the presence of Mg2+, binds G-C containing sequences in the minor groove. The SV40 early promoter contains six G-C decanucleotide sequences, which are binding sites for the transcriptional activating factor, Sp1. Each of the six Sp1 binding sites of this promoter is protected from DNAse 1 digestion by mithramycin binding. Mithramycin binding to the G-C rich sequences in the SV40 early promoter prevents subsequent protein binding to these sequences. The gel retardation of the SV40 early promoter fragment incubated with a HeLa cell extract is completely abrogated by pretreatment of the DNA fragment with mithramycin. The functional significance of mithramycin binding is reflected in the ability of mithramycin to block promoter function. Mithramycin inhibits promoter dependent transcription in an in vitro runoff transcription system in a concentration dependent manner. This suggests that mithramycin prevents transcriptional activation of the SV40 early promoter by blocking binding of transcriptional activating proteins to G-C rich promoter regions.
A Phase II, Randomized, Double-blind, Placebo-controlled Multicenter Trial of Endostar in Patients With Metastatic Melanoma
Authors: Chuanliang Cui, Lili Mao, Zhihong Chi, Lu Si, Xinan Sheng, Yan Kong, Siming Li, Bin Lian, Kangsheng Gu, Min Tao, Xin Song, Tongyu Lin, Xiubao Ren, Shukui Qin, Jun Guo
Journal: Molecular Therapy (2013)

Endostatin is a potent endogenous angiogenic inhibitor with implicated antitumor activity. However, efficacy of recombinant human endostatin (rhES) in clinical trials is controversial, and application of rhES in treatment of metastatic melanoma awaits further investigations. This phase II trial evaluated the efficacy and safety of a soluble and stable rhES (Endostar) plus dacarbazine in patients with metastatic melanomas that contains no mutations in c-kit and BRAF genes. A total of 110 patients received placebo plus dacarbazine (250 mg/m², n = 54) or Endostar (7.5 mg/m²) plus dacarbazine (250 mg/m², n = 56). The primary end points were progression-free survival (PFS) and overall survival (OS). Median PFS in the Endostar plus dacarbazine arm was 4.5 months versus 1.5 months in the placebo plus dacarbazine arm (hazard ratio (HR) = 0.578; P = 0.013). There were statistically significant improvements in OS (median, 12.0 months versus 8.0 months; HR, 0.522; P = 0.005) in favor of the Endostar plus dacarbazine arm. The regimen was generally well tolerated and had a manageable toxicity profile. Our trial suggests that Endostar plus dacarbazine is well tolerated in patients with metastatic melanoma harboring no genetic mutations popular for targeted therapy and yields a significant improvement in PFS and OS.
Activation of Matrix Metalloproteinases Precedes Left Ventricular Remodeling in Hypertensive Heart Failure Rats
Authors: Yasushi Sakata, Kazuhiro Yamamoto, Toshiaki Mano, Nagahiro Nishikawa, Junichi Yoshida, Masatsugu Hori, Takeshi Miwa, Tohru Masuyama
Journal: Circulation (2004)

Matrix metalloproteinases (MMPs) are activated in dilated failing hearts, and angiotensin-converting enzyme (ACE) inhibition prevents left ventricular (LV) dilatation. However, it remains unclear whether activation of MMPs precedes or is secondary to LV remodeling, and an effect of ACE inhibition on MMPs is unknown.Dahl salt-sensitive rats fed a high-salt diet from 8 weeks served as the hypertensive heart failure (HF) model. LV echo, histological study, measurement of mRNA levels, and gelatin zymography were performed before (at 23 weeks) and after (at 26 weeks) the development of LV dilatation and pulmonary edema. The same procedures were conducted in the HF model rats treated with a subdepressor dose of ACE inhibitor (enalapril 5 mg x kg(-1) x d(-1)) from 9 weeks. Rats fed on normal chow served as age-matched controls. In the untreated HF model rats, gene expression of MMP-2 and MMP-9 and tissue gelatinase activity were elevated at 23 weeks without LV dilatation. LV dilatation, LV systolic dysfunction, and pulmonary edema occurred at 26 weeks, with further enhancement of the expression and activity of MMPs. ACE inhibition prevented such geometrical and functional deterioration. The gene expression and activity of MMPs were suppressed by ACE inhibition at 23 weeks without a decrease in blood pressure, and the suppressive effects continued at 26 weeks.MMPs are likely to trigger and promote LV remodeling, and ACE inhibition directly exerts inhibitory effect on MMPs, leading to the prevention of LV remodeling and dysfunction.
Biokinetics of nuclear fuel compounds and biological effects of nonuniform radiation.
Authors: S Lang, K Servomaa, V M Kosma, T Rytömaa
Journal: Environmental Health Perspectives (1995)

Environmental releases of insoluble nuclear fuel compounds may occur at nuclear power plants during normal operation, after nuclear power plant accidents, and as a consequence of nuclear weapons testing. For example, the Chernobyl fallout contained extensive amounts of pulverized nuclear fuel composed of uranium and its nonvolatile fission products. The effects of these highly radioactive particles, also called hot particles, on humans are not well known due to lack of reliable data on the extent of the exposure. However, the biokinetics and biological effects of nuclear fuel compounds have been investigated in a number of experimental studies using various cellular systems and laboratory animals. In this article, we review the biokinetic properties and effects of insoluble nuclear fuel compounds, with special reference to UO2, PuO2, and nonvolatile, long-lived beta-emitters Zr, Nb, Ru, and Ce. First, the data on hot particles, including sources, dosimetry, and human exposure are discussed. Second, the biokinetics of insoluble nuclear fuel compounds in the gastrointestinal tract and respiratory tract are reviewed. Finally, short- and long-term biological effects of nonuniform alpha- and beta-irradiation on the gastrointestinal tract, lungs, and skin are discussed.
GP leader warns of exodus from the profession
Authors: G. Iacobucci
Journal: BMJ (2014)

The chair of the Royal College of General Practitioners will next week urge the government to act to avert a potential exodus from the profession, as ongoing pressure prompts more UK trained doctors to consider early retirement or working overseas.

Speaking ahead of the college’s annual conference in Liverpool on 2-4 October, Maureen Baker warned that the United Kingdom was letting good doctors “slip through our fingers” and said that urgent action was required to try to prevent more doctors leaving the UK workforce.

Figures released on 19 September by the Health and Social Care Information Centre showed that UK GPs have seen their income fall for the seventh successive year in …
My Journey to DNA Repair
Authors: Tomas Lindahl
Journal: Genomics Proteomics & Bioinformatics (2012)

Abstract I completed my medical studies at the Karolinska Institute in Stockholm but have always been devoted to basic research. My longstanding interest is to understand fundamental DNA repair mechanisms in the fields of cancer therapy, inherited human genetic disorders and ancient DNA. I initially measured DNA decay, including rates of base loss and cytosine deamination. I have discovered several important DNA repair proteins and determined their mechanisms of action. The discovery of uracil-DNA glycosylase defined a new category of repair enzymes with each specialized for different types of DNA damage. The base excision repair pathway was first reconstituted with human proteins in my group. Cell-free analysis for mammalian nucleotide excision repair of DNA was also developed in my laboratory. I found multiple distinct DNA ligases in mammalian cells, and led the first genetic and biochemical work on DNA ligases I, III and IV. I discovered the mammalian exonucleases DNase III (TREX1) and IV (FEN1). Interestingly, expression of TREX1 was altered in some human autoimmune diseases. I also showed that the mutagenic DNA adduct O6-methylguanine (O6mG) is repaired without removing the guanine from DNA, identifying a surprising mechanism by which the methyl group is transferred to a residue in the repair protein itself. A further novel process of DNA repair discovered by my research group is the action of AlkB as an iron-dependent enzyme carrying out oxidative demethylation.
Mortality study of workers in 1,3-butadiene production units identified from a chemical workers cohort.
Authors: E M Ward, J M Fajen, A M Ruder, R A Rinsky, W E Halperin, C A Fessler-Flesch
Journal: Environmental Health Perspectives (1995)

The International Agency for Research on Cancer has given the designations of "sufficient evidence" of carcinogenicity of 1,3-butadiene in experimental animals and "limited evidence" of carcinogenicity in humans. To investigate the carcinogenic effect in humans, we conducted a cohort mortality study among 364 men who were assigned to any of three 1,3-butadiene production units located within several chemical plants in the Kanawha Valley of West Virginia, including 277 men employed in a U.S. Rubber Reserve Plant which operated during World War II. The butadiene production units included in this study were selected from an index developed by the Union Carbide Corporation, which listed for each chemical production unit within their South Charleston, West Virginia and Institute, West Virginia, plants all products, by-products, and reactants. Departments included in the study were those where butadiene was a primary product and neither benzene nor ethylene oxide was present. A total of 185 deaths were observed; the standardized mortality ratio (SMR) for all causes of death was 91, reflecting lower mortality among the study population than the U.S. population. The study found a significantly elevated standardized mortality ratio (SMR) for lymphosarcoma and reticulosarcoma based on four observed cases (SMR = 577; 95% CI = 157-1480), which persisted in an analysis using county referent rates. An excess of lymphosarcoma and reticulosarcoma among all workers and among workers with routine exposure to 1,3-butadiene was also observed in the only other cohort of 1,3-butadiene production workers previously studied.(ABSTRACT TRUNCATED AT 250 WORDS)
Can an airway challenge test predict respiratory diseases? A population-based international study
Authors: Alessandro Marcon, Isa Cerveri, Matthias Wjst, Josep Antó, Joachim Heinrich, Christer Janson, Deborah Jarvis, Bénédicte Leynaert, Nicole Probst-Hensch, Cecilie Svanes, Kjell Toren, Peter Burney, Roberto de Marco
Journal: Journal of Allergy and Clinical Immunology (2013)
Catatonia is the Rosetta Stone of psychosis
Authors: Brendan T. Carroll, Tressa D. Carroll
Journal: Behavioral and Brain Sciences (2005)

Recurrent complex visual hallucinations (RCVH) represent a form of psychosis. It may be useful to compare RCVH to another form of psychosis, catatonia. Both include a long list of medical illnesses and have been examined using several different hypotheses. Catatonia has a variety of hypotheses, including neurocircuitry, neurochemistry, and an integrated neuropsychiatric hypothesis. This hypothesis for catatonia supports Collerton et al.'s Perception and Attention Deficit model (PAD) for RCVH.
PERIPHERAL NEURITIS AS A SEQUELA OF SPINAL ANESTHESIA
Authors: Lewis H. Loeser
Journal: JAMA (1933)

During the past year I have encountered five cases of peripheral neuritis following spinal anesthesia. The frequency of this complication in my experience would suggest that it is a more frequent complication than the literature would indicate and that the presence of an inflammatory syndrome affecting isolated peripheral nerves has not been clearly recognized by other observers.  Case reports illustrating neurologic complications of spinal anesthesia are becoming quite numerous. Of these, the most common is that of paralysis of the sixth nerve. Blatt,1in 1929, had collected more than a hundred such case reports and the number is considerably higher at this date.  Numerous observers have reported clinical and postmortem changes in the central nervous system following spinal anesthesia. Pathologic changes have been reported by Nonne and Demme,2Spielmeyer,3Lindemulder,4Maclachlan5and others. The observations are usually those of degenerative changes in the cord, demyelinization
X. Cardiac Arrhythmias
Authors: Robert M. Stanzler
Journal: New England Journal of Medicine (1966)

THE cardiac arrhythmias are among the most serious and alarming conditions encountered in the practice of medicine. Often, the urgency of the situation leads the physician to place undue and premature emphasis on the electrocardiographic diagnosis to the exclusion of concern for the patient as a whole. The following discussion attempts to provide guidelines for the rational approach to the patient with a cardiac arrhythmia.General Therapeutic ConsiderationsThe modern physician has at his disposal a wide array of therapeutic measures for the control of arrhythmic disorders. The selection of treatment should be based upon the urgency of the situation, . . .