tbuckley/cabot-search huggingface dataset:
<i>PNPLA3</i>variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease
Authors: Elizabeth K. Speliotes, Johannah L. Butler, Cameron D. Palmer, Benjamin F. Voight, Joel N. Hirschhorn
Journal: Hepatology (2010)

Abstract Single nucleotide polymorphisms (SNPs) near 7 loci have been associated with liver function tests or with liver steatosis by magnetic resonance spectroscopy. In this study we aim to test whether these SNPs influence the risk of histologically-confirmed nonalcoholic fatty liver disease (NAFLD). We tested the association of histologic NAFLD with SNPs at 7 loci in 592 cases of European ancestry from the Nonalcoholic Steatohepatitis Clinical Research Network and 1405 ancestry-matched controls. The G allele of rs738409 in PNPLA3 was associated with increased odds of histologic NAFLD (odds ratio [OR] = 3.26, 95% confidence intervals [CI] = 2.11-7.21; P = 3.6 × 10−43). In a case only analysis of G allele of rs738409 in PNPLA3 was associated with a decreased risk of zone 3 centered steatosis (OR = 0.46, 95% CI = 0.36-0.58; P = 5.15 × 10−11). We did not observe any association of this variant with body mass index, triglyceride levels, high- and low-density lipoprotein levels, or diabetes ( P &gt; 0.05). None of the variants at the other 6 loci were associated with NAFLD. Conclusion: Genetic variation at PNPLA3 confers a markedly increased risk of increasingly severe histological features of NAFLD, without a strong effect on metabolic syndrome component traits.
Reconfiguration of surgical, emergency, and trauma services
Authors: Adnan A Hyder
Journal: BMJ (2004)

Screening without evidence of efficacy Thyroid ultrasonography is another exampleEditor-I agree with Law's view of screening, that screening of unproved value should not be advocated. 1 As a clinical endocrinologist I often have to deal with patients' anxieties about non-palpable incidental findings on thyroid ultrasonography, often performed for wrong or unjustified reasons.Sometimes patients arrive with already established surgical complications after unnecessary thyroid operations.Although a substantial number of incidental thyroid nodules may be histologically malignant, 2 their clinical importance has never been proved.A recent preliminary study indicates that the progression rate of non-palpable proved thyroid malignant nodules to clinically significant lesions may be very low. 3 Thyroid ultrasonography is an additional example of an often used, often non-efficacious screening modality that may lead to "cascade iatrogenesis." 4
CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma
Authors: J Chu, Y Deng, D M Benson, S He, T Hughes, J Zhang, Y Peng, H Mao, L Yi, K Ghoshal, X He, S M Devine, X Zhang, M A Caligiuri, C C Hofmeister, J Yu
Journal: Leukemia (2013)
The Usefulness of Medroxyprogesterone Acetate in the Treatment of Advanced Cancer.
Authors: Leonard Sadoff
Journal: Annals of Internal Medicine (1973)

Meeting Abstracts1 May 1973The Usefulness of Medroxyprogesterone Acetate in the Treatment of Advanced Cancer.Leonard Sadoff, M.D.Leonard Sadoff, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-830_5 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAlthough the important role of progestational agents in the palliation of advanced endometrial cancer is well established, the beneficial effect of progestins in other malignancies is not generally appreciated. British investigators, in particular, have reported objective remissions with the use of progestins in cancer of the kidney, breast, ovary, and prostate. During the past 2 years we have treated more than 30 patients with medroxyprogesterone acetate, a potent synthetic progestational steroid, at doses ranging from 300 mg daily to 600 mg weekly, intramuscularly. Objective antitumor responses were seen in 4 of 20 patients with female breast carcinoma; 2 of 2,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Los Angeles, California. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDINITROCHLOROBENZENE SENSITISATION TEST IN WOMEN ON HORMONAL CONTRACEPTIVESUrinary Estrogen Excretion in Men with Advanced Cancer 1 May 1973Volume 78, Issue 5Page: 830-831KeywordsBreast cancerCancer treatmentOvariesRenal cancer Issue Published: 1 May 1973 PDF DownloadLoading ...
Left atrial enlargement. Echocardiographic assessment of electrocardiographic criteria.
Authors: A D Waggoner, A V Adyanthaya, M A Quinones, J K Alexander
Journal: Circulation (1976)

A comparison of electrocardiographic manifestations of left atrial enlargement (LAE) and left atrial size by echocardiography was made in 307 patients in sinus rhythm. Electrocardiographic criteria used were L:P wave duration in lead II equal to or greater than 0.12 sec; Va: the ratio of the duration of negative terminal P in V1 to the P-R segment equal to or greater than 1.0; Vb: a negative P terminal force in V1 less than -0.03 mm sec. The echocardiographic diagnosis of left atrial enlargement was based on 1) transverse dimension greater than 4.0 cm; or 2) a ratio of transverse atrial to transverse aortic root dimension greater than 1.17. In the presence of left atrial enlargement, a combination of criteria occurred more often than a single criterion. The overall predictive index of the electrocardiogram for left atrial enlargement was 63% (excluding criterion Vb raised probability to 80%); and that for absence of left atrial enlargement was 78%. The index of coarse versus fine fibrillary waves was unreliable in predicting left atrial enlargement. Changes in P wave morphology may be used as a reasonably specific but less sensitive indicator of left atrial enlargement.
Calcium supplementation of the diet.
Authors: S. N. Shah
Journal: BMJ (1989)

The Acheson report contains some novel pro- posals but acknowledges the current shortage of trained and skilled public health doctors to fill the posts of director of public health or district control of infection officer.But there seems to be a rush to fill these posts in many districts, particularly in North West Thames Region.If these posts are filled with unqualified and inexperienced doctors the consequences will be lingering and far reaching.As a singlehanded microbiologist I join Pro- fessor Casewell in his plea for implementing the Royal College of Pathologists' recommendation for appointing a second consultant microbiologist immediately in some larger district general hos- pitals.If this proves difficult an interim measure would be to combine the post of district control of infection officer and second microbiologist in some districts.There are several qualified and experi- enced senior registrars in microbiology who, with a short training in public health, could fill these posts.
Role of the 293b-sensitive, slowly activating delayed rectifier potassium current, iKs, in pacemaker activity of rabbit isolated sino-atrial node cells
Authors: M Lei
Journal: Cardiovascular Research (2002)

Objectives: (i) to characterize the electrophysiological properties of the slowly activating delayed rectifier potassium current, iKs, defined as the 293b-sensitive current, during the action potential (AP) of rabbit sino-atrial node (SAN) pacemaker cells; (ii) to evaluate the contribution of iKs to the pacemaker AP under physiological conditions and during β-adrenergic stimulation. Methods: Rabbit SAN pacemaker cells were studied using the perforated patch clamp technique in voltage–, AP– and current–clamp modes. Results:Voltage–clamp findings. Block of iKs by 293b is dose-dependent, with an IC50 (half block) in rabbit SAN cells of 1.35 μM and an IC80 (sub-maximal block) of 5 μM. Sub-maximal concentrations of 293b have no significant effects on long-lasting and transient inward calcium currents, iCa,L and iCa,T, inward hyperpolarization activated current, if, and transient outward current, ito. AP–clamp experiments. The 293b-sensitive current activates near the peak of the SAN pacemaker action potential, reaches a mean maximal current density of 1.0±0.3 pA/pF (n=8, cell capacitances 27 to 62 pF, mean 35±4.0 pF) during late repolarization, and inactivates towards the end of repolarization. Additionally, in two smaller cells (cell capacitances 15 and 23 pF), no discernible 293b-sensitive current component was detected. Current–clamp data. In spontaneously beating SAN cells under control conditions, sub-maximal block of iKs by 5 μM 293b has negligible effects on action potential characteristics and does not change average cycle length (n=11). In contrast, after pre-treatment with 10 nM isoprenaline to mimic β-adrenergic stimulation, cells showed a 293b-induced depolarization of maximum diastolic potential by 2.2±1%, a decrease in diastolic depolarization rate by 9.9±4%, and a slowing of late action potential repolarization by 28.7±10.2%, resulting in a prolongation of spontaneous cycle length by 9.8±3.0% (P<0.05, n=10; for all parameters). Conclusion: Our findings suggest that in rabbit SAN: (i) iKs is activated during the normal pacemaker AP; (ii) the contribution of iKs to beating rate is small under control conditions; and (iii) iKs contributes significantly to spontaneous pacemaker rate during β-adrenergic stimulation.
Payment for Pap Smears
Authors: Louise R. Levy
Journal: Annals of Internal Medicine (1990)

Letters and Corrections1 October 1990Payment for Pap SmearsLouise R. LevyLouise R. LevySearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-113-7-560_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: The article by Eddy (1) affirming that a Pap smear once every 3 years can reduce a woman's risk for dying from cervical cancer by 90% was extremely interesting. Many of us who have had this or similar types of cancer and are living today can attest to this fact. However, many women do not get this procedure done because they have to pay for it. Pap smears are not covered by most medical insurance. This is regrettable, because the procedure is not expensive and it can save so many lives.It is imperative that the public...Reference1. Eddy D. Screening for cervical cancer. Ann Intern Med. 1990;113: 214-26. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1990Volume 113, Issue 7Page: 560-561KeywordsCervical cancer Issue Published: 1 October 1990 PDF downloadLoading ...
A practical approach to an old problem
Authors: Ben Moore
Journal: BMJ (2007)

A spell of gynaecological work in central Africa provided a reminder of major problems still existing in many parts of the world, including the morbidity and mortality from neglected cervical cancer. By chance the African experience was followed almost immediately by a medical attachment in southern India that gave insight into how this problem might be tackled.

The first move was to a general hospital in eastern Zambia, a job involving three surgical and two outpatient sessions per week. At the clinics some complaints were ever present, including infertility (always the largest group) and pelvic and abdominal masses, plus two smaller groups: young women with urinary incontinence (mostly from obstructed labour) and older women with pelvic pain and foul vaginal discharge—a combination almost invariably heralding a cervical neoplasm. Of the last two groups the latter was more to be pitied. Fistula surgery was available but for advanced cervical …
Evidence for a Gene Involved in Multiple and Diverse Rearrangements in the Drosophila Genus
Authors: E. Puerma, D. J. Orengo, M. Aguade
Journal: Molecular Biology and Evolution (2014)

In Drosophila, chromosomes have been extensively reorganized during evolution, with most rearrangements affecting the gene order in chromosomal elements but not their gene content. The level of reorganization and the evidence for breakpoint reuse vary both between and within elements. The subito gene stands out as a gene involved in multiple rearrangements both because of its active single-gene transposition and because it is the nearest gene to diverse rearrangements breakpoints. Indeed, subito has undergone three single-gene transpositions and it is the nearest gene to the breakpoints of other single-gene transpositions and of two chromosomal inversions. Given that subito is involved in meiosis and therefore active in the female germ line, the high number of nearby fixed breakages might be related among others to the presumed high accessibility of the subito region to the machinery associated with double-strand breaks repair. A second important contributor would be the reduced and simple regulatory region of subito, which would imply that a fraction of the rearrangements originating from subito nearby breakages would have not affected either its pattern or timing of expression and would have, thus, not resulted in reduced fitness.
More on the need for boosters 15 years after neonatal vaccination
Authors: Cho‐Yu Chan, Shou‐Dong Lee
Journal: Hepatology (2005)

In the recent issue of HEPATOLOGY, Lu et al.1 reported that vaccinees' anti-HBs titer waned gradually following neonatal immunization with plasma-derived hepatitis B vaccine. They suggested determining the vaccinees' anti-HBs status at 10 to 15 years after receiving hepatitis B vaccine and administering one or more booster immunizations for seronegative subjects. Their findings were inconsistent with several recent studies, including one of their previous studies published in 2003, which indicated booster doses were not necessary for adolescents who had received neonatal immunization with plasma-derived hepatitis B vaccine.2-8 In fact, the data shown by Lu et al. do not fully support their proposition. First, they revealed that only one (4%) of the 26 adolescents who had been infected by hepatitis B virus (HBV), i.e., those with anti-HBc, after the age of 18 months became HBsAg-positive. Therefore, in spite of frequent hepatitis B exposure or infection during childhood in this high-risk group, the possibility of becoming a carrier was quite low. Second, their study did not provide any direct evidence to support the hypothesis that adolescents born to HBeAg-positive mothers without a "protective" level of anti-HBs are at high risk to get HBV infection or become HBV carrier. Third, the data from the remaining 113 study subjects seemed not supportive for the conclusion because most of them had unknown maternal HBsAg status and no follow-up tests were performed after the last dose of primary vaccination. Finally, low titer responders to neonatal hepatitis B vaccination usually have a weak response to a booster; therefore, it is hardly expected a booster may have long-termed benefit to this group of vaccinees. The authors drew the conclusions mainly based on the observation of the declining of anti-HBs during the follow-up period. However, the following points should be considered: (1) protection may be dependent on immune memory; and (2) encouragement of safe sex practice other than vaccination, may probably be a more cost-effective method for the prevention of HBV infection among adolescents. The necessity of booster vaccination for prevention of hepatitis B has been a debatable issue in the last decade. As the strategy of booster vaccination may cause an immense impact to national medical resources, its cost-benefit must be cautiously evaluated. Cho-Yu Chan* , Shou-Dong Lee* , * National Yang-Ming University School of Medicine, Taipei, Taiwan, Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Karachi's quiet revolutionary
Authors: Khabir Ahmad
Journal: BMJ (2004)

A 76 year old philanthropist who provides ambulances and welfare centres for Pakistan's poor people now wants to start a non-profit drug company. Abdul Sattar Edhi tells Khabir Ahmad of his plans 

Pakistan is a nation where rich people can obtain medical services that are as good as any in the world but where poor people have little access to health care. One man who has tackled this inequity head on is 76 year old Abdul Sattar Edhi, whose charity—the Edhi Welfare Trust—spends around one billion rupees (£10m; $17.5m; €14.5m) a year on projects for people who are destitute, abandoned, or mentally ill.

In a country where all too often government ambulances are used by hospital administrators and their families as private transport, Edhi's fleet of 750 ambulances in more than 100 cities is often the only means of transport for sick, wounded, or dead people. A charge is made for the journeys, but it is a nominal amount. And the charity also runs 300 welfare centres.

Despite the impressive size of his charitable trust today, Edhi comes from a humble background. He grew up in Gujarat state in India and was educated only up to the end of primary school. He and his family migrated from India to Pakistan at the partition …
Primary splenic hairy cell leukemia — remission for 21 years following splenectomy
Authors: Thomas J. Myers, Yasuo Ikeda, Stanley Schwartz, Angelo B. Pharmakidis, Mario G. Baldini
Journal: American Journal of Hematology (1981)

Abstract A patient with primary splenic hairy cell leukemia is reported. This patient presented with massive splenomegaly and pancytopenia due to hypersplenism. Exploratory laparotomy failed to demonstrate any disease outside the spleen and splenic hilar lymph nodes. Splenectomy was the only form of treatment. During the following 21 years, no recurrent hairy cell leukemia has been found. This case allows speculation that hairy cell leukemia may originate in the spleen and that prolonged survivial or cure of the disease after Splenectomy alone may be due to removal of stem cells in the spleen.
Antianginal drugs and relationship between epicardial ST segment depression and moderate regional myocardial blood flow reduction in experimental partial coronary artery occlusion
Authors: G. B Timogiannakis, C. B Kourouklis, E. N Chlapoutakis, P. K Toutouzas
Journal: Cardiovascular Research (1990)

The aim of the study was to determine whether moderate reduction in regional myocardial blood flow is related to epicardial ST segment depression and to the changes in grade and extent induced in this variable by antianginal drugs.Blood flow through the anterior descending coronary artery was reduced to 25-30% of control in open chest dogs, using a cuff flow meter as a monitor, and glyceryl trinitrate, propranolol and nifedipine were infused 60 min later. Regional left ventricular blood flow was measured with 15 mu radioactive microspheres and electrocardiograms were recorded from the epicardial surface of the anterior left ventricular wall before and after administration of the drugs.20 adult male greyhounds were used, weighing 19-24 kg.Under control conditions there was a poor correlation between ST segment depression and regional flow. Neither glyceryl trinitrate nor nifedipine had any significant effect on ST segment depression in sites overlying zones with a flow range of 80-105% of normal flow. On the other hand, glyceryl trinitrate, but not nifedipine, decreased ST segment depression in sites overlying the central ischaemic zone (35-80% of control posterior wall flow). With propranolol, mean ST depression was decreased significantly in sites overlying the central ischaemic zone (35-80% of control flow), but not in sites overlying zones with flows ranging from 80-105% of normal. Propranolol reduced blood flow to all zones.Epicardial ST segment depression is unreliable for the quantitative exploration of the grade and extent of myocardial ischaemia.
Study of erythropoietin in treatment of anaemia in patients with rheumatoid arthritis
Authors: E A Murphy, A L Bell, J Wojtulewski, M Brzeski, R Madhok, H A Capell
Journal: BMJ (1994)

Anaemia often occurs in patients with rheumatoid arthritis, and its cause is often multifactorial.The effect of erythropoietin on such anaemia is controversial, and evidence exists that cytokines may affect haemopoiesis, possibly by affecting sensitivity to erythropoietin.'-3We assessed the therapeutic efficacy of human recombinant erythropoietin in the anaemia of chronic disease in rheumatoid arthritis in a random- ised, double blind, placebo controlled study over 20 weeks.
Primary nocturnal enuresis in children with vesicoureteric reflux.
Authors: C Bacopoulos, T Karpathios, J Panagiotou, P Nicolaidou, P Androulakakis, J Messaritakis
Journal: BMJ (1987)

Coagulation studies in cases of intrauterine death: overkill?In many obstetric units coagulation profiles are performed on all women with abruptions, moderate to severe pre-eclampsia, and intrauterine fetal death.While not doubting their value in the first two cases, we wondered whether t'he routine use of these tests in all cases of intrauterine fetal death can be'justified.
Postextrasystolic potentiation and its contribution to the beat-to-beat variation of the pulse during atrial fibrillation.
Authors: S M Hardman, M I Noble, W A Seed
Journal: Circulation (1992)

BACKGROUND Beat-to-beat variations in the pulse during atrial fibrillation (AF) have conventionally been attributed to time-dependent changes in filling. We have explored the possibility that they are dependent on the intrinsic myocardial interval force relation. METHODS AND RESULTS Left ventricular (LV) contractility (maximum rate of rise of pressure, LV dP/dtmax) and ascending aortic blood velocity were measured during cardiac catheterization in 15 patients with AF. Beats preceded by an interval of less than 500 msec were excluded from analysis to reduce the confounding influence of incomplete mechanical restitution. The LV dP/dtmax was then related to the prepreceding interval. An inverse relation consistent with postextrasystolic potentiation was obtained in all 15 patients (Spearman's rank correlations, -0.56 to -0.86; p less than or equal to 0.0001). This relation was confirmed in three patients during pacing that overrode the AF and introduced single-interval variations into steady-state pacing. The ECG sequences from six of the AF patients were used to drive isometrically contracting guinea pig papillary muscle and human right ventricular tissue (n = 7); the same inverse relation was demonstrated. On a beat-by-beat basis, the maximum rate of rise of force in the isolated muscle correlated well with LV dP/dtmax in the patients (r = 0.50-0.86, p less than or equal to 0.0001). The relation of the integral of aortic velocity (AVI, proportional to stroke volume) to prepreceding interval was also inverse, whereas important correlations were demonstrated between LV dP/dtmax and AVI (Spearman's rank correlations, 0.27-0.95; p less than or equal to 0.0001). CONCLUSIONS This study demonstrates that postextrasystolic potentiation contributes to the characteristic beat-to-beat variation of the pulse in AF.
Ceftazidime-Avibactam: a Novel Cephalosporin/β-lactamase Inhibitor Combination
Authors: George G. Zhanel, Christopher D. Lawson, Heather Adam, Frank Schweizer, Sheryl Zelenitsky, Philippe R. S. Lagacé-Wiens, Andrew Denisuik, Ethan Rubinstein, Alfred S. Gin, Daryl J. Hoban, Joseph P. Lynch, James A. Karlowsky
Journal: Drugs (2013)