tbuckley/cabot-search huggingface dataset:
Effect of Recombinant ApoA-I Milano on Coronary Atherosclerosis in Patients With Acute Coronary Syndromes
Authors: Steven E. Nissen, Taro Tsunoda, E. Murat Tuzcu, Paul Schoenhagen, Christopher J. Cooper, Muhammad Yasin, Gregory M. Eaton, Michael A. Lauer, W. Scott Sheldon, Cindy L. Grines, Stephen Halpern, Tim Crowe, James C. Blankenship, Richard Kerensky
Journal: JAMA (2003)

<h3>Context</h3> Although low levels of high-density lipoprotein cholesterol (HDL-C) increase risk for coronary disease, no data exist regarding potential benefits of administration of HDL-C or an HDL mimetic. ApoA-I Milano is a variant of apolipoprotein A-I identified in individuals in rural Italy who exhibit very low levels of HDL. Infusion of recombinant ApoA-I Milano–phospholipid complexes produces rapid regression of atherosclerosis in animal models. <h3>Objective</h3> We assessed the effect of intravenous recombinant ApoA-I Milano/phospholipid complexes (ETC-216) on atheroma burden in patients with acute coronary syndromes (ACS). <h3>Design</h3> The study was a double-blind, randomized, placebo-controlled multicenter pilot trial comparing the effect of ETC-216 or placebo on coronary atheroma burden measured by intravascular ultrasound (IVUS). <h3>Setting</h3> Ten community and tertiary care hospitals in the United States. <h3>Patients</h3> Between November 2001 and March 2003, 123 patients aged 38 to 82 years consented, 57 were randomly assigned, and 47 completed the protocol. <h3>Interventions</h3> In a ratio of 1:2:2, patients received 5 weekly infusions of placebo or ETC-216 at 15 mg/kg or 45 mg/kg. Intravascular ultrasound was performed within 2 weeks following ACS and repeated after 5 weekly treatments. <h3>Main Outcome Measures</h3> The primary efficacy parameter was the change in percent atheroma volume (follow-up minus baseline) in the combined ETC-216 cohort. Prespecified secondary efficacy measures included the change in total atheroma volume and average maximal atheroma thickness. <h3>Results</h3> The mean (SD) percent atheroma volume decreased by −1.06% (3.17%) in the combined ETC-216 group (median, −0.81%; 95% confidence interval [CI], −1.53% to −0.34%;<i>P</i>= .02 compared with baseline). In the placebo group, mean (SD) percent atheroma volume increased by 0.14% (3.09%; median, 0.03%; 95% CI, −1.11% to 1.43%;<i>P</i>= .97 compared with baseline). The absolute reduction in atheroma volume in the combined treatment groups was −14.1 mm<sup>3</sup>or a 4.2% decrease from baseline (<i>P</i>&lt;.001). <h3>Conclusions</h3> A recombinant ApoA-I Milano/phospholipid complex (ETC-216) administered intravenously for 5 doses at weekly intervals produced significant regression of coronary atherosclerosis as measured by IVUS. Although promising, these results require confirmation in larger clinical trials with morbidity and mortality end points.
Novel truncating mutations in<i>PKP1</i>and<i>DSP</i>cause similar skin phenotypes in two Brazilian families
Authors: A. Tanaka, J.E. Lai-Cheong, M.E.M. Café, B. Gontijo, P.R. Salomão, L. Pereira, J.A. McGrath
Journal: British Journal of Dermatology (2009)

Inherited mutations in components of desmosomes result in a spectrum of syndromes characterized by variable abnormalities in the skin and its appendages, including blisters and erosions, palmoplantar hyperkeratosis, woolly hair or hypotrichosis and, in some cases, extracutaneous features such as cardiomyopathy. We investigated the molecular basis of two Brazilian patients presenting with clinical features consistent with ectodermal dysplasia-skin fragility syndrome. In patient 1 we identified a homozygous nonsense mutation, p.R672X, in the PKP1 gene (encoding plakophilin 1). This particular mutation has not been reported previously but is similar to the molecular pathology underlying other cases of this syndrome. In patient 2 we found compound heterozygosity for two frameshift mutations, c.2516del4 and c.3971del4, in the DSP gene (encoding desmoplakin). Although there was considerable clinical overlap in the skin and hair abnormalities in these two cases, patient 2 also had early-onset cardiomyopathy. The mutation c.3971del4 occurs in the longer desmoplakin-I isoform (which is the major cardiac transcript) but not in the more ubiquitous desmoplakin-II. In contrast, PKP1 is not expressed in the heart, which accounts for the lack of cardiomyopathy in patient 1. Collectively, these cases represent the first desmosomal genodermatoses to be reported from Brazil and add to genotype-phenotype correlation in this group of inherited disorders. Loss-of-function mutations in the DSP gene can result in a phenotype similar to ectodermal dysplasia-skin fragility syndrome resulting from PKP1 mutations but only DSP pathology is associated with cardiac disease.
Randomized Trial of a Nonpolymer-Based Rapamycin-Eluting Stent Versus a Polymer-Based Paclitaxel-Eluting Stent for the Reduction of Late Lumen Loss
Authors: Julinda Mehilli, Adnan Kastrati, Rainer Wessely, Alban Dibra, Jörg Hausleiter, Birgit Jaschke, Josef Dirschinger, Albert Schömig
Journal: Circulation (2006)

Background— Although drug-eluting stents (DESs) constitute a major achievement in preventing restenosis, concerns remain regarding the increased inflammatory and thrombogenic responses associated with the polymers used. Recently, we showed that a nonpolymer on-site coating with rapamycin not only is feasible and safe but also leads to a dose-dependent reduction in restenosis. Methods and Results— To assess whether polymer-free stents coated on-site with 2% rapamycin solution are inferior to polymer-based paclitaxel-eluting stents for the prevention of restenosis, we randomly assigned a total of 450 patients with de novo lesions in native coronary vessels, excluding the left main trunk, to either the polymer-free, rapamycin-coated Yukon DES (rapamycin stent) or the polymer-based, paclitaxel-eluting Taxus stent (paclitaxel stent). The primary end point was in-stent late lumen loss. Secondary end points were angiographic restenosis and target lesion revascularization. The study was designed to test the noninferiority of the rapamycin stent compared with the paclitaxel stent with respect to late lumen loss according to a noninferiority margin of 0.13 mm. Follow-up angiography was completed in 81% of the patients. The mean difference in in-stent late lumen loss between the rapamycin-stent group and the paclitaxel-stent group was 0.002 mm, and the upper limit of the 1-sided 95% confidence interval was 0.10 mm ( P =0.02 from test for noninferiority). No significant differences were observed regarding angiographic restenosis rates (14.2% with the rapamycin stent and 15.5% with the paclitaxel stent) and target lesion revascularization rates due to restenosis (9.3% in both groups). Conclusions— The polymer-free, rapamycin-coated stent has an antirestenotic effect that is not inferior to that observed with the polymer-based paclitaxel-eluting stent.
Charity aims to distribute donated drugs to developing countries
Authors: Kathryn Godfrey
Journal: BMJ (2004)

A charity was launched last week with the aim of obtaining in-date medicines from UK pharmaceutical companies and distributing them to countries in the developing world. The work of International Health Partners UK (IHP) will be modelled on that of its Canadian partner organisation, which has in the past 10 years distributed drugs overseas with a wholesale value of $C150m (£67m; $125m; €96m).

The organisation will seek donations of quality in-date medicines and medical supplies from UK drug companies and distribute them in accordance with WHO guidelines and Red Cross protocols.

The organisation estimates that up to £100m of suitable drugs …
Approaches to Drug Discovery
Authors: Alfred Burger
Journal: New England Journal of Medicine (1964)

THE history of early drug discovery is essentially that of a random search for therapeutic agents from plants, animals and naturally occurring minerals. The medicine men and priests of many tribes and faiths tried out such natural materials, or aqueous or alcoholic extracts prepared from them, and by trial and error, over the centuries, established a materia medica that was transmitted from one generation to another with only relatively minor alterations.1 The botanical drugs and the preparations from animal tissues and some inorganic materials, used before the nineteenth century, represented a motley array of more or less toxic mixtures that . . .
Development of Luminescent pH Sensor Films for Monitoring Bacterial Growth Through Tissue
Authors: Fenglin Wang, Yash Raval, Hongyu Chen, Tzuen‐Rong J. Tzeng, John D. DesJardins, Jeffrey N. Anker
Journal: Advanced Healthcare Materials (2013)

Although implanted medical devices (IMDs) offer many benefits, they are susceptible to bacterial colonization and infections. Such infections are difficult to treat because bacteria could form biofilms on the implant surface, which reduce antibiotics penetration and generate local dormant regions with low pH and low oxygen. In addition, these infections are hard to detect early because biofilms are often localized on the surface. Herein, an optical sensor film is developed to detect local acidosis on an implanted surface. The film contains both upconverting particles (UCPs) that serve as a light source and a pH indicator that alters the luminescence spectrum. When irradiated with 980 nm light, the UCPs produce deeply penetrating red light emission, while generating negligible autofluorescence in the tissue. The basic form of the pH indicator absorbs more of upconversion luminescence at 661 nm than at 671 nm and consequently the spectral ratio indicates pH. Implanting this pH sensor film beneath 6-7 mm of porcine tissue does not substantially affect the calibration curve because the peaks are closely spaced. Furthermore, growth of Staphylococcus epidermidis on the sensor surface causes a local pH decrease that can be detected non-invasively through the tissue.
Capillary testing in an anticoagulant clinic: comparison of two methods
Authors: S M Donohue, J M K Dufty, N A Kafkarkou, R Kirwan, D A Taberner
Journal: BMJ (1996)

Complaints from patients about the discomfort associated with capillary testing by lancets, and discrepancy between the results of capillary and venous prothrombin time testing prompted a search for an alternative method of sampling. Automatic capillary testing devices have been successfully used in children1 and were found to be less painful by patients and easy to use by technologists when piloted in our anticoagulant clinic. We tested one such device, the Tenderlett, in our clinic.

Ethics committee approval was obtained from the New River Health Authority. All patients in a routine anticoagulant clinic were asked to participate in the study after they had been given oral and written explanations. Thirty seven patients (50% of total attenders) gave written consent and were asked to have two capillary tests—one with the usual lancet method and one with a Tenderlett device (ITC, Margate, UK)—and a venepuncture. The international normalised ratio …
Gene Flow between Species of Lake Victoria Haplochromine Fishes
Authors: Irene E. Samonte, Yoko Satta, Akie Sato, Herbert Tichy, Naoyuki Takahata, Jan Klein
Journal: Molecular Biology and Evolution (2007)

The haplochromine cichlid fishes of Lake Victoria (LV), East Africa, are a textbook example of adaptive radiation—a rapid divergence of multiple morphologically distinguishable forms from a few founding lineages. The forms are generally believed to constitute a "flock" of several hundred reproductively isolated species in a dozen or so genera. This belief has, until now, not been subjected to a test, however. Here, we compare genetic variation at 11 loci in 10 haplochromine populations of 6 different species. Although the genetic diversity in the populations is quite high, using a variety of statistical tests, we find no evidence of genetic differentiation among the populations of LV haplochromines. On genetic distance trees, populations of the same species intermingle with those of different species. At the molecular level, the species are indistinguishable from one another. Genetic comparisons with closely related species in 2 crater lakes indicate that the species within LV continue exchanging genes. These observations have important implications for phylogenetic reconstruction. The approach used in this study is applicable to other instances of adaptive radiation.
A NEW PRINCIPLE IN IRRIGATION OF THE URETHRA WITH INSTRUMENT.
Authors: J. H. BACON
Journal: JAMA (1907)

I have been using a new principle in the treatment of gonorrhea, and the results seem to me to be good. The difference between my method of treating gonorrhea and that of those who use irrigations is not medicinal but mechanical. Instead of using only the force of pressure from gravity for irrigation of the urethra, I have added a bulb to the irrigation tube, and by intermittent pressing obtain an intermittent or rather a rhythmic pressure. The value of this kind of pressure over simple pressure was brought to my mind by seeing the blood vessels pulsate in the thigh of one of my patients while I was irrigating and remembering that the blood will not continue to circulate if the pressure is steady. It is only when the pressure is rhythmic that the blood will pass through the capillaries. Now. if we use Nature's method we must use
A fairly learned society
Authors: C. Douglas
Journal: BMJ (1996)

Specialist societies, with their rituals, camaraderie, and comforting internal politics, constitute one of the unsung glories of British medicine. So it was our great pleasure here in Auchendreich last week to host a meeting of one of the larger, more influential, and generally more worth while examples of the breed.

I should at this point declare an interest. I have been a member of this particular society since the mid 1970s, when as a pale young registrar I presented to one of its scientific sessions a paper which concluded that though the area of study was of some importance the number of subjects had …
The Precautionary Principle in the Context of Mobile Phone and Base Station Radiofrequency Exposures
Authors: Mike Dolan, Jack Rowley
Journal: Environmental Health Perspectives (2009)

No health hazard has been established from exposure to radiofrequency fields up to the levels recommended by the International Commission on Non-Ionizing Radiation Protection. However, in response to public concern and the perceived level of scientific uncertainty, there are continuing calls for the application of the precautionary principle to radiofrequency exposures from mobile phones and base stations.We examined the international evolution of calls for precautionary measures in relation to mobile phones and base stations, with particular focus on Australia and the United Kingdom.The precautionary principle is difficult to define, and there is no widespread agreement as to how it should be implemented. However, there is a strong argument that precautionary measures should not be implemented in the absence of reliable scientific data and logical reasoning pointing to a possible health hazard. There is also experimental evidence that precautionary advice may increase public concern.We argue that conservative exposure standards, technical features that minimize unnecessary exposures, ongoing research, regular review of standards, and availability of consumer information make mobile communications inherently precautionary. Commonsense measures can be adopted by individuals, governments, and industry to address public concern while ensuring that mobile networks are developed for the benefit of society.
Changes in glycosylated haemoglobin after poor control in insulin-dependent diabetics.
Authors: A P Brooks, I M Nairn, J D Baird
Journal: BMJ (1980)

Glycosylated haemoglobin (HbA1) was measured in seven insulin-dependent diabetic patients before, during, and after a seven-day period of monitored poor control. There was considerable individual variation in the pattern and degree of change in HbA1 concentration induced by poor control and the time when it occurred. Greater increases in HbA1 were seen during the period of metabolic derangement than in the subsequent two months. More information is required before HbA1 estimations are widely used clinically to monitor control in individual diabetics.
Advisory Group Insists on 'Alternative' Voice
Authors: Charles Marwick
Journal: JAMA (1994)

THE FIRST FORMAL meeting of the newly designated Advisory Council to the Office of Alternative Medicine (OAM) at the National Institutes of Health (NIH), Bethesda, Md, was acrimonious almost to the point of failure. That the meeting concluded on a more or less positive note was due only to the fact that some council members apologized for untimely remarks and to the skillful diplomacy of Ruth Kirchstein, MD, the NIH's deputy director. Among the alternative medical approaches the OAM may study are homeopathy, nutritional therapies, acupuncture, herbal remedies, and interactive mind-body and meditation techniques, along with such specific treatments as, for example, the use of shark cartilage for cancer therapy (<i>JAMA</i>. 1993;270: 1400). <h3>Out of Their Hands</h3> The principal thorn in the advisory committee members' side was the fact that the OAM was preparing to announce the funding of several study centers without asking, as is customary, for the committee's
Twenty five years of HIV infection in haemophilic men in Britain: an observational study
Authors: Caroline A Sabin, Andrew N Phillips, Thynn Thynn Yee, Anja Griffioen, Christine A Lee
Journal: BMJ (2005)

a twofold higher mortality by 65 than those who continued working (1.89, 1.58 to 2.27).The mortality by 65 of employees who retired at 60 was similar to those who continued working at 60 (1.04, 0.82 to 1.31).
Evaluating computerised health information systems: Opportunities were missed
Authors: W. J Winkelman
Journal: BMJ (2003)

EDITOR—Littlejohns et al describe a failed attempt to implement a computerised information system among 42 hospitals in the Limpopo province of South Africa. They provide a typology of possible reasons for this failure, retrospectively summarising the lessons learnt.1

Implementing an information system can be viewed as an organisational innovation process that contributes to the maintenance and improvement of its overall performance and …
Effect of Outcome on Physician Judgments of Appropriateness of Care
Authors: Robert A. Caplan
Journal: JAMA (1991)

Is a permanent injury more likely to elicit a rating of inappropriate care than a temporary injury? To explore this question, we asked 112 practicing anesthesiologists to judge the appropriateness of care in 21 cases involving adverse anesthetic outcomes. The original outcome in each case was classified as either temporary or permanent. The authors then generated a matching alternate case identical to the original in every respect except that a plausible outcome of opposite severity was substituted. The original and alternate cases were randomly divided into two sets and assigned to reviewers who were blind to the intent of the study. The reviewers were asked to rate independently the care in each case as appropriate, less than appropriate, or impossible to judge, based on their personal (implicit) judgment of reasonable and prudent practice. A significant inverse relationship between severity of outcome and judgments of appropriateness of care was observed in 15 (71%) of the 21 matched pairs of cases. Overall, the proportion of ratings for appropriate care decreased by 31 percentage points when the outcome was changed from temporary to permanent and increased by 28 percentage points when the outcome was changed from permanent to temporary. We conclude that knowledge of the severity of outcome can influence a reviewer's judgment of the appropriateness of care.
X-ray diffraction studies of the composition of gallstones from English and Australian patients
Authors: D. J. Sutor, S. E. Wooley
Journal: Gut (1969)

The crystalline composition of two collections of gallstones from patients in England and Australia have been determined by the x-ray powder diffraction technique. Twelve substances have been identified including a form of cholesterol which hitherto has not been reported. The weighted percentage composition averaged over each collection shows that cholesterol is the major constituent of the Australian stones and cholesterol and cholesterol monohydrate the major constituents of the English calculi. The cholesterol is possibly a decomposition product of the monohydrate. The calcium carbonates-calcite, aragonite, and vaterite-constitute most of the remainder of the calculi. Although their percentage composition is much smaller than that of the cholesterols, they are nevertheless present in a high proportion of stones. Small traces of apatite, whitlockite, sodium chloride, calcium stearate and palmitic acid (or other long-chain compounds having closely related spacings) have been found. Small spheroids scattered throughout some stones appear to be mainly calcium stearate, although the total quantity available is too small and too impure for a definite identification.
A translocation X;Y system for detecting meiotic nondisjunction and chromosome breakage in males of Drosophila melanogaster.
Authors: P A Foureman
Journal: Environmental Health Perspectives (1979)

A nondisjunction and chromosome breakage screening system devised by Craymer and modified in our laboratory, involves an X;Y translocation with the short arm of the Y (Ys), marked with the wild type allele of yellow, attached to the distal end of an X (break point 11D) carrying the recessive marker y; and the long arm of the Y chromosome (YL), marked with the dominant locus Bar of Stone (BS), attached to the proximal end of the X. A female tester strain carrying normal chromosomes homozygous for the yellow allele is employed in the mating scheme. Following normal disjunction in the male, all zygotes, which in this case receive aneuploid paternal sex-chromosomes and a normal euploid maternal complement, will die as a result of genetic imbalance. Thus all survivors from this corss can be classified as exceptions arising from: (1) nondisjunction in the female; (2) gross deletion of the paternal X;Y chromosome; (3) complete loss of the paternal X;Y chromosome; or (4) primary meiotic nondisjunction in the male. Results indicate the sensitivity of this scheme for the detection of events induced by x-rays and various chemicals. Positive results have been obtained with the known mutagens EMS and x-radiation.
Familial Persistent Hyperinsulinemic Hypoglycemia of Infancy and Mutations in the Sulfonylurea Receptor
Authors: Mark J. Dunne, Charlotte Kane, Ruth M. Shepherd, Jorge A. Sanchez, Roger F.L. James, Paul R.V. Johnson, Albert Aynsley-Green, Shan Lu, John P. Clement, Keith J. Lindley, Susumu Seino, Lydia Aguilar-Bryan, Gabriela Gonzalez, Peter J. Milla
Journal: New England Journal of Medicine (1997)

Persistent hyperinsulinemic hypoglycemia of infancy is caused by inappropriate and excessive secretion of insulin. Although the disease is rare in outbred communities (approximately 1 case per 50,000 persons), the incidence is approximately 1 per 2500 in inbred Arabic communities in which there is a familial (autosomal recessive) form of the disease. The disease most commonly presents with severe hypoglycemia a few hours after birth, although some cases present after several weeks or months. Some patients have a response to treatment with diazoxide or somatostatin, but others require partial pancreatectomy to control the hyperinsulinism.1–3 It has recently been suggested2, . . .