tbuckley/cabot-search huggingface dataset:
William Frederick Colburn
Authors: M Colburn
Journal: BMJ (2002)

Professor of medicine whose famous report on inequality and health fell foul of the Thatcher government Sir Douglas Black was one of medicine's most important and well loved individuals.His many achievements included a professorship of medicine in Manchester, research on salt and water balance, persuading the profession in the 1940s and 1950s that the NHS was a good thing, and the presidency of the Royal College of Physicians.But he is best known for his 1980 Black report, which spelt out the social inequalities in health and proposed ways of reducing them.In 1977 the then Labour government's health secretary, David Ennals, chaired an expert committee investigating why the NHS had apparently failed to reduce social inequalities in health, and he commissioned Black to write a report.The result was published-or, rather, suppressed-in 1980, when the Conservatives had come to power.The Black report was not to Mrs Thatcher's liking and was never printed; instead, 260 photocopies were distributed in a half hearted fashion on Bank Holiday Monday.However, the report had a huge impact on political thought in the United Kingdom and overseas.It led to an assessment by the Office for Economic Co-Operation and Development and the World Health Organization of health inequalities in 13 countries-though not on UK government policy.Penguin Books later published a shorter version of the report.Black provided convincing figures that showed what many suspected-that the poorest had the highest rates of ill health and death.He argued that these rates could not be explained solely by income, education, mobility, or lifestyle, but were also caused by a lack of a coordinated policy that would ensure uniform delivery of services.He recommended health goals, tax changes, benefit increases, and restrictions on the sale and advertising of tobacco.Patrick Jenkin, the social services secretary, estimated with a shudder that Black's proposals-which he hinted were little short of outrageouswould cost an unthinkable £2bn a year.Thin, gentle mannered, poker faced, and self effacing, Black was deeply moral, always serious, and frequently extremely funny.His after dinner speeches were received with rapt attention, as to miss a moment of that soft Scottish voice was to miss a joke.He
Suppression of Frequently Recurring Genital Herpes
Authors: Stephen E. Straus, Howard E. Tariff, Mindell Seidlin, Susan Bachrach, Lloyd Lininger, John J. DiGiovanna, Karl A. Western, Holly A. Smith, Sandra Nusinoff Lehrman, Teresa Creagh-Kirk, David W. Alling
Journal: New England Journal of Medicine (1984)

We studied 35 otherwise healthy adults with frequently recurring genital herpes (greater than or equal to 1 episode per month), in a double-blind trial comparing oral acyclovir with placebo capsules for suppression of recurrent infection. The patients were treated for 125 days unless herpes recurred. Among 32 evaluable patients, there were significantly fewer recurrences during acyclovir treatment (4 of 16) than during placebo treatment (16 of 16, P less than 0.001). The mean duration of therapy was significantly longer for patients receiving acyclovir than for those receiving placebo (114.9 vs. 24.8 days, P less than 0.001). Of 19 patients who had recurrences in the blind trial, only 2 had recurrences when given acyclovir in a second, open-study phase. All patients had recurrences after completing acyclovir treatment. The therapy was well tolerated, with minimal gastrointestinal upset and one hypersensitivity reaction. Studies of the viral isolates demonstrated that lesions developing in patients receiving acyclovir contained drug-resistant virus. Later recurrences in these patients were associated with drug-sensitive virus. We conclude that oral acyclovir suppresses genital herpes in patients with frequent recurrences, but the potential for problems with drug resistance and the long-term safety need to be more fully explored.
Elusive Diagnosis of Left Ear Nodules
Authors: Shinko Koko Lin, Mark Philip Guralnick, David Samuel Cassarino
Journal: JAMA Dermatology (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Primary gastric, duodenal, and rectal signet ring cell carcinoma revealed by cutaneous metastasis
Authors: Z. Ismaili, S. Dekhay, A. Moussaoui, A. Jahid
Journal: Endoscopy (2011)

We report a particularly interesting case of cutaneous metastases, which revealed three sites of signet ring cell carcinoma. A 50-year-old woman presented with painless cutaneous nodules, along with a change in bowel habit and weight loss. She had no history of rectal bleeding. Skin examination revealed multiple nodules on the left side of her neck ([Fig. 1 a]), below her right breast, on her back in a zoster-like distribution, and in the perineal region ([Fig. 1 b]).
Effects of Noise on Hearing
Authors: W. W. Clark
Journal: JAMA (1999)

FEW WOULD DENY THAT WE LIVE IN A NOISY WORLD. NOISE, whether a result of air traffic, crowded urban streets, personal stereos, or high-powered machinery, rifles, and shotguns, is one of America’s most widespread nuisances. Excessive noise disrupts sleep, produces stress, impairs communication, and, in high enough doses, causes significant noise-induced hearing loss (NIHL). Although roughly 25% of all Americans ages 65 and older suffer hearing loss, hearing loss is not part of the natural aging process. Much hearing loss in older Americans is due to preventable, noiseinduced wear and tear on the auditory system.
Walter Edward Spencer Bain
Authors: D R Pugh
Journal: BMJ (2008)

<h3>ABSTRACT</h3> Understanding the pharmacogenomics of opioid metabolism and behavior is vital to therapeutic success as mutations can dramatically alter therapeutic efficacy and addiction liability. We found robust, sex-dependent BALB/c substrain differences in oxycodone behaviors and whole brain concentration of oxycodone metabolites. BALB/cJ females showed robust state-dependent oxycodone reward learning as measured via conditioned place preference when compared to the closely related BALB/cByJ substrain. Accordingly, BALB/cJ females also showed a robust increase in brain concentration of the inactive metabolite noroxycodone and the active metabolite oxymorphone compared to BALB/cByJ mice. Oxymorphone is a highly potent full agonist at the mu opioid receptor that could enhance drug-induced interoception and state-dependent oxycodone reward learning. Quantitative trait locus (<b>QTL</b>) mapping in a BALB/c F2 reduced complexity cross revealed one major QTL on chromosome 15 underlying brain oxymorphone concentration that explained 32% of the female variance. BALB/cJ and BALB/cByJ differ by fewer than 10,000 variants which can greatly facilitate candidate gene/variant identification. Hippocampal and striatal cis-expression QTL (eQTL) and exon-level eQTL analysis identified <i>Zhx2</i>, a candidate gene coding for a transcriptional repressor with a private BALB/cJ retroviral insertion that reduces Zhx2 expression and sex-dependent dysregulation of CYP enzymes. Whole brain proteomics corroborated the Zhx2 eQTL and identified upregulated CYP2D11 that could increase brain oxymorphone in BALB/cJ females. To summarize, Zhx2 is a highly promising candidate gene underlying brain oxycodone metabolite levels. Future studies will validate <i>Zhx2</i> and its site of action using reciprocal gene editing and tissue-specific viral manipulations in BALB/c substrains. <h3>Significance Statement</h3> Our findings show genetic variation can result in sex-specific alterations in whole brain concentrations of bioactive opioid metabolites following oxycodone administration, and reinforces the need for sex as a biological factor in pharmacogenomic studies. The co-occurrence of female-specific increased oxymorphone and state-dependent reward learning suggests that this minor yet potent and efficacious metabolite of oxycodone could increase opioid interoception and drug-cue associative learning of opioid reward which has implications for cue-induced relapse of drug-seeking behavior.
Structural insight into<i>Helicobacter pylori</i>DNA replication initiation
Authors: Laurent Terradot, Anna Zawilak-Pawlik
Journal: Gut Microbes (2010)

While increasing knowledge is accumulating about the molecular mechanisms allowing the human pathogen Helicobacter pylori to survive and to subvert host defenses, much less is known about fundamental aspects of its biology, including DNA replication. We have studied the initiation step of chromosome replication of H. pylori and particularly the interaction between the initiator protein DnaA and its recently identified regulator HobA. This work has recently culminated in the determination of the crystal structure of the domains I and II of DnaA (DnaA(I-II)) in complex with HobA. By combining the structure with a variety of biochemical experiments we show that a tetramer of HobA can accommodate up to four DnaA molecules organized in a particular conformation within the complex. Mutations of the HobA interface that impaired the binding with DnaA were designed and proved to be lethal once introduced into H. pylori. These features suggest that HobA provides a molecular scaffold onto which regular oligomers of DnaA can assemble. The HobA-promoted oligomerization of DnaA could have a determinant role in the formation of the open complex. We propose a speculative model of HobA-dependent DnaA oligomerization leading to DNA unwinding. More generally, the parallel we draw with Escherichia coli DnaA and DiaA (HobA-like E. coli protein) will direct new studies that will contribute to the understanding of bacterial DNA replication.
Lack of new drugs is reaching crisis point, says review
Authors: R. Dobson
Journal: BMJ (2003)

The number of new drugs approved in the United States last year fell to half the annual average over the past five years.

Only 15 new drugs were approved by the Food and Drug Administration in 2002, compared with a five year annual average of 31, says an editorial in Nature Reviews Drug Discovery (2003:2:3).

It warns that the fall in the number of new drugs is reaching crisis point and says that new drug applications are down worldwide.

It says that the European parliament's environment committee has asked Thomas Lonngren, executive director of …
Induction of Long-term Glycemic Control in Newly Diagnosed Type 2 Diabetic Patients Is Associated With Improvement of β-Cell Function
Authors: Yanbing Li, Wen Xu, Zhihong Liao, Bin Yao, Xiahua Chen, Zhimin Huang, Guoliang Hu, JianPing Weng
Journal: Diabetes Care (2004)

OBJECTIVE—To investigate whether long-term optimal glycemic control can be achieved without medication by transient continuous subcutaneous insulin infusion (CSII) and the possible mechanisms responsible for this remission. RESEARCH DESIGN AND METHODS—Newly diagnosed type 2 diabetic patients (n = 138, fasting glucose &amp;gt;11.1mmol/l) were hospitalized and treated with CSII for 2 weeks. Intravenous glucose tolerance tests (IVGTTs) were performed, and blood glucose, HbA1c, lipid profiles, proinsulin, insulin, and C-peptide were measured before and after CSII. Patients were followed longitudinally on diet alone after withdrawal of insulin. RESULTS—Optimal glycemic control was achieved within 6.3 ± 3.9 days by CSII in 126 patients. The remission rates (percentages maintaining near euglycemia) at the third, sixth, twelfth, and twenty-fourth month were 72.6, 67.0, 47.1, and 42.3%, respectively. Patients who maintained glycemic control &amp;gt;12 months (remission group) had greater recovery of β-cell function than those who did not (nonremission group) when assessed immediately after CSII. Homeostasis model assessment of β-cell function (HOMA-B) and the area under the curve (AUC) of insulin during IVGTT were higher in the remission group (145.4 ± 89.6 vs. 78.5 ± 68.5, P = 0.002, and 1,423.4 ± 523.2 vs. 1,159.5 ± 476.8 pmol · l−1 · min−1, P = 0.044). Change in acute insulin response was also greater in the remission group than that in the nonremission group (621.8 ± 430.4 vs. 387.3 ± 428.8 pmol · l−1 · min−1, P = 0.033). CONCLUSIONS—Short-term intensive insulin therapy can induce long-term glycemic control in newly diagnosed type 2 diabetic patients with severe hyperglycemia. The improvement of β-cell function, especially the restoration of first-phase insulin secretion, could be responsible for the remission.
CLINICAL NOTES ON PATIENTS FROM THE MIDDLE NORTHWEST INFECTED WITH ENTAMEBAS
Authors: H. Z. GIFFIN
Journal: JAMA (1913)

on liage one finds an ovarian hematoma or hemorrhage into a lutein cyst, which is probably tbe fundamental cause of the hemorrhage.I do supravaginal hysterec- tomy and appendectomy in these cases. SUMMAIÎY OF OASES STUDIEDThe total number of eases studied was 227.Sixty-nine cases of fibromyoma uteri and 2 cases of carci- noma uteri which never presented symptoms of menorrhagia or metforrhagia.Forty-five cases, pathologic diagnosis of endometritis.Operations performed: complete hysterectomy in 5 eases (past menopause) ; anterior bysterotomy and curettage in 1 ease; vaginal hysterectomy in 2 cases; dilatation and curettage in 37 eases.Twenty-one cases, pathologic diagnosis of fibromyoma with endometritis.*Operations performed!supravaginal hysterec- tomy in 17 eases; complete hysterectomy in .'icases; vaginal hysterectomy in 1 case.Twenty-four cases, pathologic diagnosis of carcinoma.Operations performed: complete hysterectomy in 12 cases; supravaginal hysterectomy in 4 eases; dilatation, curettage and cauterization in 1 case; dilatation and curettage ill 1 cuse: cauterization in 1 ease; vaginal hysterectomy in 1 case-, 4 cases inoperable.Forty-four cases, pathologie diagnosis fibromyoma.Operations performed: siipravaginal hysterectomy in 31 eases; complete hysterectomy in 7 eases; anterior bysterotomy in 2 cases; myomectomy in 3 cases; vaginal hysterectomy in 1 ease.Two cases, pathologic diagnosis sareomatoiis degeneration of fibroid uteri, siipravaginal hysterectomy being performed in both cases.Mortality.-Fourdeaths, all occurring in eases of carcinoma.In one'carcinoma also involved the sigmoid and the patient developed fecal fistula; one patient died of uremia and two of tpxemia, 1634 Walnut Street.
Clustering of Minimal Deleted Regions Reveals Distinct Genetic Pathways of Human Hepatocellular Carcinoma
Authors: Yuh-Shan Jou, Chih-Shia Lee, Ya-Hui Chang, Chin-Fu Hsiao, Chian-Feng Chen, Chuan-Chuan Chao, Lawrence S.H. Wu, Shiou-Hwei Yeh, Ding-Shinn Chen, Pei-Jer Chen
Journal: Cancer Research (2004)

Abstract Systematic scan and statistical analysis of loss of heterozygosity (LOH) has been widely used to define chromosomal aberrations in various cancers for cloning of tumor suppressor genes and for development of prognostic markers. However, the establishment of novel strategies is needed, so that the nonrandom but heterogeneous chromosomal aberration data could provide significant insights into our understanding of molecular pathogenesis of cancers. After comprehensive allelotyping of recurrent allelic losses with 441 highly informative microsatellite markers and overlapping LOH regions on human hepatocellular carcinoma (HCC) chromosomes, 33 minimal deleted regions (MDRs) were revealed. Five and 15 of the 33 MDRs have physical intervals in less than 5 and 10 Mb, respectively, with the smallest MDR9p1 of 2.2 Mb located at 9p21.3-p21.2. Statistical and Kaplan-Meier survival analysis revealed a significant association between the loss of MDR15q1 (15q21.1-q22.2) and the HCC patient survival (adjusted P = 0.033). After cluster analysis of 33 MDRs that represented LOH profiles of each HCC tissue based on clinicopathological features and p53 mutations, two major genetic pathways, low-stage and advanced-stage HCC, were uncovered based on high concordance of MDR clusters. We propose that the definition of genome-wide MDRs on the cancer genome not only narrows down the location of existing tumor suppressor genes to facilitate positional candidate cloning and develop potential prognostic markers after statistical association of MDRs with clinicopathological features but also dissects genetic interactions and pathways of chromosomal aberrations in tumorigenesis.
Management of depression in general practice.
Authors: S Brandon
Journal: BMJ (1986)

I Management of depression in general practiceMany patients consulting general practitioners show signs of sadness or depression; such patients are at high risk ofhaving psychoactive drugs prescribed.The rise in the volume of anxiolytic and antidepressant drugs prescribed far exceeds any credible rise in the prevalence of disorders appropriately treated by them.So when should depression be treated in a
Naturally occurring anti-i/I cold agglutinins may be encoded by different VH3 genes as well as the VH4.21 gene segment.
Authors: L C Jefferies, C M Carchidi, L E Silberstein
Journal: Journal of Clinical Investigation (1993)

In the current study, we wished to determine if the V regions encoding the naturally occurring anti-i/I Cold Agglutinins (anti-i/I CA) differ from pathogenic anti-i/I CA that are exclusively encoded by the VH4.21 gene. After EBV transformation of B lymphocytes, we generated one anti-I secreting clone from each of two individuals; clone 4G (individual CM, PBL) and clone Sp1 (individual SC, spleen). Clone 4G expresses a VH3 gene sequence that is 92% homologous to the germline gene WHG26. Clone Sp1 also expresses a VH3 gene that is 98% homologous to the fetally rearranged M85/20P1 gene. Another clone, Sp2 (anti-i specificity), from individual SC is 98% homologous to the germline gene VH4.21. For correlation, we studied anti-i/I CA fractions purified from 15 normal sera and found no or relatively small amounts of 9G4 (VH4.21 related idiotype) reactive IgM. Five cold agglutinin fractions contained large amounts of VH3-encoded IgM (compared to pooled normal IgM) by virtue of their binding to modified protein Staph A (SPA), and absorption of three CA fractions with modified SPA specifically removed anti-i/I binding specificity entirely. Collectively, the data indicate that naturally occurring anti-i/I CA may be encoded to a large extent by non-VH4.21-related genes, and that the VH4.21 gene is not uniquely required for anti-i/I specificity.
Productivity in science: more more and more?
Authors: T OPTHOF, R CORONEL
Journal: Cardiovascular Research (2002)

a product of the Institute for Scientific During the first 60-70 years of the last century it was Information (ISI, Philadelphia, USA).The number of more or less possible to read everything that was published journals covered by the ISI grew by 27% from 4464 in worldwide in whatever scientific speciality.This is no 1990 to 5684 in 2000.It is possible that these numbers longer true.De Jong and Schaper [1] published a paper on may point to a better coverage of what is published by the the number of publications in clinical cardiovascularISI and that it may overestimate the real growth in the science including the citation of those papers over a 12-number of scientific journals.The number of papers year period from 1981 to 1992.Of the 137 000 papers increased by 38% from about 507 000 in 1990 to 702 000 published during that period 46% remained uncited with a in 2000.Fig. 2 shows that the number of citations almost remarkable geographical variability from 31% for Norway doubled (196%).This increase is partly based on the to 69% for Japan.It should be realized that even a single increase in published papers (Fig. 1), but to a larger extent citation by the authors themselves (self-citation) during on an increase in the references per paper (16.5 in 1990 such a long period would classify a paper in the cited and 23.3 in 2000).It is important to note that the category.Low citation is not synonymous with low references per paper are relevant to the citing papers, not to scientific quality over brief periods (as used for popular the cited papers.It is, theoretically, possible that in 2000 bibliometric parameters as the 'impact factor') [2,3].the 16.4 million citations in 702 000 citing papers went to However, zero citation of about 62 000 papers over a 6-year period after publication [1], raises the question whether the scientific community should try to limit this flood of publications.This question becomes even more relevant when it is realized that electronic publishing will probably alleviate the burden of page limitations imposed on journal editors, and may lead to rejection rates that are more in agreement with reviewer's recommendations [4].It has been pointed out previously that rejection rates are much higher than what is actually advised by reviewers [4]. .
Characterization of refractory period extension by transcardiac shock.
Authors: R J Sweeney, R M Gill, P R Reid
Journal: Circulation (1991)

BACKGROUND To better understand the refractory period extension (RPE) produced by transcardiac shocks and its possible role in defibrillation, we measured RPE under various experimental conditions. METHODS AND RESULTS Using ventricular pacing in pentobarbital-anesthetized dogs, we characterized RPE in relation to the anatomic site of pacing, the local voltage gradient (LVG) produced by the shocks at the pacing site, and the pacing rate and pacing current used to make the measurements. We also determined if RPE persisted into the next refractory period after the shock and measured RPE at the end of 30-second episodes of acute ischemia to the pacing site, which were caused by occluding the left anterior descending artery. Each anatomic site tested showed RPE, which increased sharply with increasing LVG at lower levels but less sharply at higher LVG. The RPE versus LVG was approximated with an exponential curve that had an exponential constant of about 5-6 V/cm. At faster pacing rates, RPE occurred earlier in the refractory period but was unchanged when expressed as a percent increase of refractory period. RPE did not vary with the pacing current and was present only in the refractory period during which the shock was delivered. The RPE was not significantly altered by acute ischemia. These results show that transcardiac shocks selectively extend the refractory period of tissue proportional to the LVG and the timing of the shock in the refractory period. They are consistent with the concept that RPE prevents depolarization from tissue directly excited by a shock from propagating to tissue that was refractory to that same shock. CONCLUSIONS The insensitivity of RPE to short ischemic episodes and the presence of RPE at increased activation rates suggest that RPE might exist under conditions of fibrillation and be a major determinant of the success or failure of defibrillation.