tbuckley/cabot-search huggingface dataset:
Molecular characterization of a new family with α-Thalassemia-1 (——MA mutation)
Authors: Ana Villegas, Jesus Sanchez, Dolores L. Carreno, Paloma Ropero, Fernando A. Gonzalez, Domingo Espinos, Maria A. Penalver, Matilde Lozano
Journal: American Journal of Hematology (1995)

Abstract A Spanish family with α‐thalassemia‐1 (α‐Thal‐1), deletion (— MA ), is described. In addition to the loss of 22 kb of DNA with a deletion of the α 1 , α 2 , α 1 , α 2 , and Ψζ 1 genes, a triplication of the ζ gene cluster in “cis” is produced. The structure of this triplication is formed by the Ψα 1 , gene, the interzeta region, and, possibly, the insertion of the Ψα 2 fragment. © 1995 Wiley‐Liss, Inc.
Matrix Metalloproteinase-9 Pretreatment Level Predicts Intracranial Hemorrhagic Complications After Thrombolysis in Human Stroke
Authors: Joan Montaner, Carlos A. Molina, Jasone Monasterio, Sonia Abilleira, Juan F. Arenillas, Marc Ribó, Manolo Quintana, José Alvarez-Sabín
Journal: Circulation (2003)

Background— Matrix metalloproteinase (MMP) expression is related to blood brain barrier disruption after cerebral ischemia. Moreover, MMP inhibitors reduce hemorrhagic transformation (HT) after embolic ischemia in tissue plasminogen activator (t-PA)–treated animals. We aimed to correlate plasmatic MMP levels with the appearance of intracranial bleeding complications in stroke patients treated with t-PA. Methods and Results— Serial MMP-2 and MMP-9 determinations were performed (ELISA, ng/mL) in 41 strokes involving the middle cerebral artery territory in patients who received t-PA within 3 hours of stroke onset. Blood samples were obtained at baseline (pretreatment) and at 12 and 24 hours after symptom onset. Hemorrhagic events were classified according to CT criteria (petechial hemorrhagic infarctions [HI, 1 to 2] and large parenchymal hemorrhages [PH, 1 to 2]). Brain CT scan was obtained at 48 hours or when a neurological worsening occurred. HT was present in 36.5% of the patients (24.4% HI and 12.1% PH). MMP-2 values were unrelated to any subtype of HT. The highest baseline MMP-9 level (normal range &lt;97 ng/mL) corresponded to patients who later developed a PH (PH: 270.2±87.8, non-HT: 126.3±127.5, HI: 94.6±88.7; P =0.047). A graded response was found between mean baseline MMP-9 levels and the degree of bleeding (HI-1=37.4; HI-2=111.0; PH-1=202.5; PH-2=337.8). Baseline MMP-9 was the most powerful predictor of PH appearance in the multiple logistic regression model (OR= 9.62; CI 1.31 to 70.26; P =0.025). Conclusions— Baseline MMP-9 level predicts PH appearance after t-PA treatment. Therefore, we suggest that MMP determination may increase the safety profile for thrombolysis and, in the future, anti-MMP drugs might be combined with t-PA to prevent hemorrhagic complications.
Drug‐induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters
Authors: M.C.Y. Heng, M.K. Song, J. Harker, M.K. Heng
Journal: British Journal of Dermatology (2000)

Background Phosphorylase kinase (PhK), also known as adenosine triphosphate (ATP)-phosphorylase b phosphotransferase, integrates multiple calcium/calmodulin-dependent signalling pathways, including those involved in cell migration and cell proliferation, while coupling these pathways to glycogenolysis and ATP-dependent phosphorylation, thus ensuring continuing energy supply for these activities. Objectives Our laboratory recently reported correlation of elevated PhK activity with psoriatic activity. This study further evaluates the significance of drug-induced suppression of PhK activity on psoriatic activity. Patients and methods PhK activity was assayed in four groups, each with 10 patients: (i) active untreated psoriasis; (ii) resolving psoriasis treated by calcipotriol (Dovonex®, Bristol Myers Squibb, Princeton, NJ, U.S.A.), a vitamin D3 analogue and an indirect inhibitor of PhK; (iii) curcumin (diferuloylmethane), a selective PhK inhibitor; and (iv) 10 normal non-psoriatic subjects. Results PhK activity in units mg−1 protein was highest in active untreated psoriasis (1204 ± 804·3; mean ± SD), lower in the calcipotriol-treated group (550·7 ± 192·9), lower in curcumin-treated group (207·2 ± 97·6), and lowest in normal skin (105·4 ± 44·6). One-way analysis of variance performed on log-transformed PhK activity measure showed significant differences among the four groups, F3,36 = 48·79, P < 0·0001. Decreased PhK activity in curcumin-and calcipotriol-treated psoriasis was associated with corresponding decreases in keratinocyte transferrin receptor (TRR) expression, severity of parakeratosis and density of epidermal CD8+ T cells. Conclusions Our results demonstrate that drug-induced suppression of PhK activity is associated with resolution of psoriatic activity as assessed by clinical, histological and immunohistochemical criteria, and support the hypothesis that effective antipsoriatic activity may be achieved through modulation of PhK activity.
Cholesterol-Lowering Therapy in Women and Elderly Patients With Myocardial Infarction or Angina Pectoris
Authors: Tatu A. Miettinen, Kalevi Pyörälä, Anders G. Olsson, Thomas A. Musliner, Thomas J. Cook, Ole Faergeman, Kåre Berg, Terje Pedersen, John Kjekshus, for the Scandinavian Simvastatin Study Group
Journal: Circulation (1997)

Background The Scandinavian Simvastatin Survival Study (4S) demonstrated pronounced reductions in mortality and major coronary events in a cohort of patients with established coronary heart disease (CHD). The present study provides a detailed, post hoc assessment of the efficacy and safety of simvastatin therapy in the following subgroups of 4S patients: those ≥65 years of age, those &lt;65 years of age, women, and men. Methods and Results The 4S cohort of 4444 CHD patients included 827 women and 1021 patients ≥65 years of age. Total cholesterol at baseline was 5.5 to 8.0 mmol/L with triglycerides ≤2.5 mmol/L. Patients were randomized to therapy with simvastatin 20 to 40 mg daily or placebo for a median follow-up period of 5.4 years. End points consisted of all-cause and CHD mortality, major coronary events (primarily CHD death and nonfatal myocardial infarction), other acute CHD and atherosclerotic events, hospitalizations for CHD and cardiovascular events, and coronary revascularization procedures. Mean changes in serum lipids were similar in the different subgroups. In patients ≥65 years of age in the simvastatin group, relative risks (95% confidence intervals) for clinical events were as follows: all-cause mortality, 0.66 (0.48 to 0.90); CHD mortality, 0.57 (0.39 to 0.83); major coronary events, 0.66 (0.52 to 0.84); any atherosclerosis-related event, 0.67 (0.56 to 0.81); and revascularization procedures, 0.59 (0.41 to 0.84). In women, the corresponding figures were 1.16 (0.68 to 1.99); 0.86 (0.42 to 1.74), 0.66 (0.48 to 0.91), 0.71 (0.56 to 0.91), and 0.51 (0.30 to 0.86), respectively. Conclusions Cholesterol lowering with simvastatin produced similar reductions in relative risk for major coronary events in women compared with men and in elderly (≥65 years of age) compared with younger patients. There were too few female deaths to assess the effects on mortality in women. Because mortality rates increased substantially with age, the absolute risk reduction for both all-cause and CHD mortality in simvastatin-treated subjects was approximately twice as great in the older patients.
CLOPIDOGREL WITH AND WITHOUT PROTON PUMP INHIBITOR USE: A PARIS REGISTRY ANALYSIS
Authors: Sameer Bansilal, Usman Baber, George Dangas, Philippe Steg, Giora Weisz, Melissa Aquino, Timothy Henry, Annapoorna Kini, Thomas Stuckey, David Cohen, Peter Berger, Ioannis Iakovou, Ron Waksman, David Antoniucci, Samantha Sartori, Bernhard Witzenbichler, Mitchell Krucoff, James Hermiller, Fayaz Shawl, C. Michael Gibson, Alaide Chieffo, David Moliterno, Maria Alu, Antonio Colombo, Roxana Mehran
Journal: Journal of the American College of Cardiology (2014)
Screening for Vaginal Cancer
Authors: Kenneth L. Noller
Journal: New England Journal of Medicine (1996)

Until recently, cancer of the uterine cervix was a major cause of death among women of reproductive age in the United States.1 In the 1960s, the pioneering work of Papanicolaou and Traut on the cytologic examination of exfoliated cells from the uterine cervix was recognized for its lifesaving potential to detect cancer, and the regular screening of women for cervical cancer — and, more important, its precursors — gradually became a routine part of medical practice.2 Nonetheless, the practice of cervical cytologic screening (the Pap smear) owes its wide acceptance not so much to public recognition of its value, but . . .
The Art of Letting Go
Authors: Ranjana Srivastava
Journal: New England Journal of Medicine (2007)

“Is there any money we need to pay? Is that why you won't treat him?”Her face wears a hunted expression; her slender frame is weighed down by fatigue and untold distress. In her native country, people died for lack of sufficient funds for treatment.“No, no,” I hurry to reassure her. “This has nothing to do with money. Health care is free here. It is just that he is not well enough to have treatment.”“Anything, doctor — we will do anything to make him better. We have three young children.”“I know.”She walks down the corridor, whispering . . .
Successful Utilization of an Immunosuppressive B Cell Depleting Regimen in an Adolescent Male with Recalcitrant Non-Infectious Colitis and X-Linked Hyper IgM Syndrome
Authors: Vivian E. Cino, Faina Shenderov, Joan Spiro, Robert Reid, Jerome Sigua, Gary I. Kleiner
Journal: Journal of Allergy and Clinical Immunology (2015)
Maize HapMap2 identifies extant variation from a genome in flux
Authors: Jer Ming Chia, Chi Song, Peter J. Bradbury, Denise Costich, Natalia De Leon, John Doebley, Robert J. Elshire, Brandon Gaut, Laura Geller, Jeffrey C. Glaubitz, Michael Gore, Kate E. Guill, Jim Holland, Matthew B. Hufford, Jinsheng Lai, Meng Li, Xin Liu, Yanli Lu, Richard McCombie, Rebecca Nelson, Jesse Poland, Boddupalli M. Prasanna, Tanja Pyhäjärvi, Tingzhao Rong, Rajandeep S. Sekhon, Qi Sun, Maud I. Tenaillon, Feng Tian, Jun Wang, Xun Xu, Zhiwu Zhang, Shawn M. Kaeppler, Jeffrey Ross-Ibarra, Michael D. McMullen, Edward S. Buckler, Gengyun Zhang, Yunbi Xu, Doreen Ware
Journal: Nature Genetics (2012)
Anuria Treated by Cortisone
Authors: H. Moore, D. K. O'Donovan
Journal: BMJ (1953)

circumstances-in particular an intelligent patient and a very alert practitioner-led to reference of the case at a much earlier stage in the development of the disease than is usual.Although clinical deterioration until treatment was instituted was rapidly progressive, it is clearly impossible to claim with any certainty that the apparent response was more than coincidental.Nevertheless the relapse associated with objective evidence of physiologically inadequate dosage, and the resumption of improvement when dosage was in- creased, as well as the remarkably complete recovery which was evident within a matter of days, render coincidence a not entirely satisfying explanation: that resolution of the condition was related to the administration of A.C.T.H. would appear to be a distinct possibility.Acute disseminated encephalomyelitis is a rare disease, and, although it is fully appreciated that no firm conclusions can be drawn from the present small series of treated cases, they are reported in the belief that the results are suggestive enough to merit similar trial on a larger scale.In the absence of any other effective or rational therapy such a trial would appear justifiable, though a word of caution is advisable.Diagnosis of acute encephalomyelitis following exanthemata is usually simple, but the "spontaneous " ex- amples, and those following non-specific infections, may present difficult diagnostic problems.Administration of A.C.T.H. to cases of virus disease such as poliomyelitis is at best useless, and recent evidence suggests that it may be actively harmful.In bacterial infections such as cerebral abscess or tuberculous meningitis its use might well be dis- astrous.For these reasons, and also in order not to confuse assessment of the value of the drug in the disease under consideration, the employment of this experimental therapy should be limited to cases of acute neurological illness in which an unequivocal diagnosis of encephalomyelitis can be competently sustained.The present paper shows that in such cases the drug is harmless if nothing more. SummarySeven cases clinically diagnosed as acute disseminated encephalomyelitis have been treated with A.C.T.H.They comprise two cases of encephalomyelitis follow- ing varicella, two cases of transverse and one case of subacute ascending myelitis, and two (familial) cases of encephalitic illness following non-specific infection, in one of which there have been recurrent encephalitic illnesses.Acute disseminated encephalomyelitis has a pronounced tendency to rapid, spontaneous, and often complete recovery, and no final conclusions regarding the efficacy or otherwise of A.C.T.H. can be reached without extended observations on a scale which would permit of statistical evaluation.It is believed that the results reported here are suggestive enough to justify further trial.I wish to thank practitioners and consultants in Region No. 1 who have been kind enough to tefer cases for treatment, Dr. G. A. Smart for help and advice on technical aspects of the use of A.C.
EFFECT OF LOW DOSE ROSUVASTATIN THERAPY ON REGRESSION OF CAROTID PLAQUE AND VASA VASORUMS IN CHINESE POPULATION: A PROSPECTs CLINICAL TRIAL BY MRI
Authors: Ruixue Du, Jianming Cai, Ye Ping, Qingjun Wang, Danqing Liu, Hongmei Wu
Journal: Journal of the American College of Cardiology (2013)
Molecular epidemiology of silent introduction and sustained transmission of wild poliovirus type 1, Israel, 2013
Authors: L M Shulman, E Gavrilin, J Jorba, J Martin, C C Burns, Y Manor, J Moran-Gilad, D Sofer, M Y Hindiyeh, R Gamzu, E Mendelson, I Grotto, None for the Genotype - Phenotype Identification (GPI) group
Journal: Eurosurveillance (2014)

Poliovirus vaccine coverage in Israel is over 90%. The last nine birth cohorts have been vaccinated exclusively with inactivated polio vaccine (IPV). However, between February and July 2013 type 1 wild poliovirus (WPV1) was detected persistently in 10 and intermittently in 8 of 47 environmental surveillance sites in southern and central Israel and in 30 stool samples collected during July from healthy individuals in southern Israel. We report results of sequence and phylogenetic analyses of genes encoding capsid proteins to determine the source and transmission mode of the virus. WPV1 capsid protein 1 nucleotide sequences were most closely related to South Asia (SOAS) cluster R3A polioviruses circulating in Pakistan in 2012 and isolated from Egyptian sewage in December 2012. There was no noticeable geographical clustering within WPV1-positive sites. Uniform codon usage among isolates from Pakistan, Egypt and Israel showed no signs of optimisation or deoptimisation. Bayesian phylogenetic time clock analysis of the entire capsid coding region (2,643 nt) with a 1.1% evolutionary rate indicated that Israeli and Egyptian WPV1-SOAS lineages diverged in September 2012, while Israeli isolates split into two sub-branches after January 2013. This suggests one or more introduction events into Israel with subsequent silent circulation despite high population immunity.
Dietary α-Lipoic Acid Supplementation Inhibits Atherosclerotic Lesion Development in Apolipoprotein E–Deficient and Apolipoprotein E/Low-Density Lipoprotein Receptor–Deficient Mice
Authors: Wei-Jian Zhang, Karyn E. Bird, Timothy S. McMillen, Renee C. LeBoeuf, Tory M. Hagen, Balz Frei
Journal: Circulation (2007)

Vascular inflammation and lipid deposition are prominent features of atherosclerotic lesion formation. We have shown previously that the dithiol compound alpha-lipoic acid (LA) exerts antiinflammatory effects by inhibiting tumor necrosis factor-alpha- and lipopolysaccharide-induced endothelial and monocyte activation in vitro and lipopolysaccharide-induced acute inflammatory responses in vivo. Here, we investigated whether LA inhibits atherosclerosis in apolipoprotein E-deficient (apoE-/-) and apoE/low-density lipoprotein receptor-deficient mice, 2 well-established animal models of human atherosclerosis.Four-week-old female apoE-/- mice (n=20 per group) or apoE/low-density lipoprotein receptor-deficient mice (n=21 per group) were fed for 10 weeks a Western-type chow diet containing 15% fat and 0.125% cholesterol without or with 0.2% (wt/wt) R,S-LA or a normal chow diet containing 4% fat without or with 0.2% (wt/wt) R-LA, respectively. Supplementation with LA significantly reduced atherosclerotic lesion formation in the aortic sinus of both mouse models by approximately 20% and in the aortic arch and thoracic aorta of apoE-/- and apoE/low-density lipoprotein receptor-deficient mice by approximately 55% and 40%, respectively. This strong antiatherogenic effect of LA was associated with almost 40% less body weight gain and lower serum and very low-density lipoprotein levels of triglycerides but not cholesterol. In addition, LA supplementation reduced aortic expression of adhesion molecules and proinflammatory cytokines and aortic macrophage accumulation. These antiinflammatory effects of LA were more pronounced in the aortic arch and the thoracic aorta than in the aortic sinus, reflecting the corresponding reductions in atherosclerosis.Our study shows that dietary LA supplementation inhibits atherosclerotic lesion formation in 2 mouse models of human atherosclerosis, an inhibition that appears to be due to the "antiobesity," antihypertriglyceridemic, and antiinflammatory effects of LA. LA may be a useful adjunct in the prevention and treatment of atherosclerotic vascular diseases.
The great medicines scandal: Next steps?
Authors: Warren A Kaplan
Journal: BMJ (2006)

Editor—The recent World Health Organization-Health Action International, Europe report on disparities in price, availability, and affordability of medicines for chronic diseases is important work.1 This entire subject matter as it relates to medicines for chronic diseases deserves wider appreciation and understanding.

It should not be allowed to be filed away on shelves to gather dust—which is a rather roundabout way of asking: “How can the contents of such a report be leveraged in effective ways?” I would suggest the following.

Firstly, teach and otherwise disseminate the contents of this report to educational institutions with courses in chronic non-communicable disease, public health, and disease management inside and outside the United States.

Secondly, encourage a dialogue between practitioners and the private sector at one or more regional or subregional meetings to discuss further the implications of this report.

Thirdly, create “access to medicines” campaigns based on existing campaigns for infectious disease medicines. Perhaps medicines for chronic non-communicable diseases require a different model?

People in resource poor countries who survive beyond their individual demographic and epidemiological transitions are already facing epidemics of diabetes and heart disease. “Access” issues regarding medicines for chronic diseases lie well under the radar for most policy makers in developing countries but these issues cannot be ignored.
Drug trafficking in Europe changes as expertise in synthetic drug production increases
Authors: R. Watson
Journal: BMJ (2013)

Europe’s illicit drugs trade is entering a new era, forcing policy makers to rethink their responses, says a report commissioned by Cecilia Malmstrom, the European commissioner for home affairs.1

Historically, the illicit drug market in Europe centred on specific drugs trafficked by specialised operators along well defined routes. Now experts note that the market is far more fluid as new routes and multi-substance consignments become more common.

Commenting on the findings, Malmstrom said, “Drug markets are evolving, and we need …
RESPONSE OF PERITONEAL TISSUE TO DUSTS INTRODUCED AS FOREIGN BODIES
Authors: JOHN W. MILLER
Journal: JAMA (1934)

The response of the body tissues to various kinds of dust has been a subject of much interest in recent years. Mavrogordato, Gardner, Gye and others have conducted experiments on the action of inhaled dusts. Kettle<sup>1</sup>has studied the response to dusts injected into the subcutaneous tissues and intratracheally, and Policard<sup>2</sup>has used the cornea and conjunctiva in his recent studies. In 1924 experiments were begun at the Pittsburgh Station of the United States Bureau of Mines to determine the action and fate of various dusts when injected into the peritoneal cavity of guinea-pigs.<sup>3</sup>The conclusions reached at that time were that live animal tissue in all parts of the body tends to react in essentially the same manner to foreign bodies and that fibrous tissue is formed in the peritoneal cavity by quartz and is not formed by limestone and coal. This paper is a continuation
ENDOTHELIAL PROGENITOR CELLS MOBILIZATION AND RECRUITMENT CORRELATE WITH CORONARY ARTERY DISEASE SEVERITY
Authors: Niccolò Mancini, Chrysanthos Grigoratos, Maria Elena Lucia Picoi, Federica Massaro, Tatiana Santoni, Ottavia Balbi, Angela Pucci, Mariachiara Barsotti, Claudia Mattioli, Paola Collecchi, Uberto Bortolotti, Generoso Bevilacqua, Rossella Di Stefano, Alberto Balbarini
Journal: Journal of the American College of Cardiology (2013)
Pain and Its Effects in the Human Neonate and Fetus
Authors: K.J.S. Anand, P.R. Hickey
Journal: New England Journal of Medicine (1987)

THE evaluation of pain in the human fetus and neonate is difficult because pain is generally defined as a subjective phenomenon.1 Early studies of neurologic development concluded that neonatal responses to painful stimuli were decorticate in nature and that perception or localization of pain was not present.2 Furthermore, because neonates may not have memories of painful experiences, they were not thought capable of interpreting pain in a manner similar to that of adults.3 4 5 On a theoretical basis, it was also argued that a high threshold of painful stimuli may be adaptive in protecting infants from pain during birth.6 These traditional . . .
Expression cloning of the epithelial sodium channel
Authors: Cecilia M. Canessa, Jean-Daniel Horisberger, Laurent Schild, Bernard C. Rossier
Journal: Kidney International (1995)

Complex organisms take sodium from the external environment to achieve and maintain extracellular volume and blood pressure. Many sodium transporter systems have evolved, and among them the epithelial sodium channel plays a fundamental role in determining the final amount of sodium reabsorbed. Epithelial sodium channels are present in the apical membrane of cells lining the distal segment of the nephron, urinary bladder, distal colon, and the airways. In the skin they are found in the sweat ducts and in certain animals (amphibians) they are also present in the epidermal cells. All these tissues absorb sodium via an amiloride-sensitive, highly selective Na +  channel. This paper discusses recent efforts that have lead to the cloning and the elucidation of the structure of the epithelial sodium channel.
Doctors must not accept inducements for referrals, GMC says
Authors: C. Dyer
Journal: BMJ (2015)

The General Medical Council has written to all UK licensed doctors to warn them that they must not accept incentives to treat patients at any particular private healthcare facility or refer them there for tests, after an investigation by the Competition and Markets Authority found that such schemes were widespread in the private health sector.1

The letters follow an order from the competition authority placing new legal requirements on doctors from 6 April, including a ban on “requesting, agreeing to receive or accepting any direct incentive or any obligation” from a private hospital to give preference to its facilities …