tbuckley/cabot-search huggingface dataset:
Therapeutic Comparison of Metformin and Sulfonylurea, Alone and in Various Combinations: A double-blind controlled study
Authors: Leif S Hermann, Bengt Scherstén, Per-Olof Bitzén, Thomas Kjellström, Folke Lindgärde, Arne Melander
Journal: Diabetes Care (1994)

OBJECTIVE To assess and compare the therapeutic efficacy and safety of metformin (M) and sulfonylurea (glyburide, G), alone and in various combinations, in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS Of 165 patients (fasting blood glucose [FBG] ≥ 6.7 mmol/l) initially treated with diet alone, 144 (FBG still ≥6.7 mmol/l) were randomized to double-blind, double-dummy controlled treatment with M, G, or primary combination therapy (MG). The dose was titrated, withFBG &amp;lt;6.7 mmol/l as target, using, at most, six dose levels. The first three dose levels comprised increasing single-drug therapy (M or G) or primary combination at increasing but low dosage (MGL), and the second three levels were composed of various high-dose combinations, i.e., add-on therapy (M/G or G/M) and primary combination escalated to high dosage (MGH). Medication was maintained for 6 months after completed dose titration. RESULTS The FBG target was achieved in 9% of patients after diet alone. Single-drug therapy was insufficient in 36% and MGL in 25% (NS) of the randomized patients. There was further improvement in glucose control by the high-dose combinations. Mean FBG ± SE was reduced (P = 0.001) from 9.1 ± 0.4 to 7.0 ± 0.2 mmol/l in those maintained on single-drug treatment or low-dose primary combination. Those treated with different high-dose combinations had a large mean FBG reduction, from 13.3 ± 0.8 to 7.8 ± 0.6 mmol/l. HbA1c levels showed corresponding reductions, and glycemic levels rose after drug discontinuation. Fasting C-peptide rose during treatment with G and MGL but not with M, while fasting insulin was not significantly changed. Meal-stimulated C-peptide and insulin levels were unchanged by M but increased by G and, to a lesser extent, by MGL. There were no significant insulin or C-peptide differences between the different high-dose combinations (M/G, G/M, and MGH). Body weight did not change following treatment with M or combination but increased by 2.8 ± 0.7 kg following G alone. Blood pressure was unchanged. Overall effects on plasma lipids were small, with no significant differences between groups. Drug safety was satisfactory, even if the reporting of (usually modest) adverse events was high; the profile, but not the frequency, differed between groups. CONCLUSIONS Dose-effect titrated treatment with either metformin or glyburide promotes equal degrees of glycemic control. The former, but not the latter, is able to achieve this control without increasing body weight or hyperinsulinemia. Near-normal glycemia can be obtained by a combination of metformin and sulfonylurea, even in advanced NIDDM.
State governments' delays in fund transfer are affecting India's national health mission, report says
Authors: C. Travasso
Journal: BMJ (2015)

Health ministry officials in Delhi are concerned that delays in the release of funds by state governments are hurting India’s National Health Mission and AIDS prevention programmes, Reuters reports.1

Although the central government has sent more than $1.3bn (Rs81bn; £0.9bn; €1.2bn) to the state treasuries for the mission since April, says the report, the funds are taking months, instead of the stipulated 15 days, to reach designated regional health societies. And this has resulted in salaries not being paid on time and delay to construction of health clinics.

The National Health Mission was established to provide affordable, accessible, …
Systemic collateral and pulmonary artery stenosis in patients with congenital pulmonary valve atresia and ventricular septal defect.
Authors: M D McGoon, R E Fulton, G D Davis, D G Ritter, C A Neill, R I White
Journal: Circulation (1977)

Angiograms of 30 patients with congenital pulmonary valve atresia, ventricular septal defect, and large systemic-pulmonary collateral arteries (SPCAs) were evaluated. All had aortography, 28 had SPCA arteriography, and 26 had right ventriculography. Seventeen (65%) of 26 patients had a right ventricular infundibulum, 23 (77%) had a pulmonary artery confluence, and five of the nine patients without a right ventricular infundibulum had a confluence. Sixty-six SPCAs of aortic origin were seen; 28 (42%) had narrowing and 21 patients (70%) had one or more narrowed SPCAs. Five patients had collaterals from internal mammary, subclavian or innominate arteries. Fourteen (47%) had hilar pulmonary artery stenosis. Of these 14 patients mild peripheral stenosis was demonstrated in five. Right aortic arch was present in 15 patients (50%). Complete angiographic delineation of pulmonary vasculature is an essential procedure for preoperative detection of pulmonary and SPCA stenoses in these patients.
Furosemide Compared With Hydrochlorothiazide
Authors: Harold R. Dettelbach
Journal: JAMA (1979)

To the Editor.—  The recent article by Araoye et al (240:1863, 1978), Furosemide Compared With Hydrochlorothiazide: Long-term Treatment of Hypertension, contains misleading statements, and the conclusions drawn are not supported by the data presented. The abstract gives in a rather categorical fashion the impression that the authors have shown hydrochlorothiazide to be a clearly superior antihypertensive agent. An examination of the article shows that this is certainly not the case.  Patients were recruited for this study on the basis of their diastolic blood pressures (BPs) (between 95 and 119 mm Hg). The authors' conclusions of increased efficacy of hydrochlorothiazide over furosemide are based entirely on observations of systolic BP. It may be valid to draw conclusions (if the data analysis had been performed properly) on the effect of these drugs on systolic pressure; it is, however, entirely misleading to make sweeping statements concerning antihypertensive effects when the primary selection criterion
Nanobody-coupled microbubbles as novel molecular tracer
Authors: Sophie Hernot, Sunil Unnikrishnan, Zhongmin Du, Talent Shevchenko, Bernard Cosyns, Alexis Broisat, Jakub Toczek, Vicky Caveliers, Serge Muyldermans, Tony Lahoutte, Alexander L. Klibanov, Nick Devoogdt
Journal: Journal of Controlled Release (2011)
496. AAV-Mediated, Somatic Gene Transfer to RPE Cells in Order To Study the Pathogenesis of Macular Degeneration: Proteomic and Genomic Analysis
Authors: Garrett C. Du Bois, Petya D. Radoeva, Jean Bennett
Journal: Molecular Therapy (2006)

Top of pageAbstract
The use of AAV-mediated gene therapy appears to be an exciting approach for the treatment of inherited retinal diseases. However, there is at present, minimal information regarding the effect on the genome and proteome of the target cell following rAAV infection. Additional studies are critically needed to determine which genes and proteins are differentially expressed as the result of rAAV infection and as a result of the inclusion of a transgene. Using ARPE-19, a retinal pigment epithelial (RPE) cell line and recombinant AAV2/5 viruses, AAV2/5.EGFP, AAV2/5.EGFP-RO (reverse orientation), AAV2/5.EFEMP1wt and EFEMP1mut, as well as uninfected cells, we have examined the proteomes by 2D differential in-gel electrophoresis (DIGE) and the genomes by RNA transcript profiling. EGFP encodes the enhanced green flourescent protein and infection of RPE cells with this virus allowed the determination of the optimal multiplicity of infection (MOI) which was 1 |[times]| 106. The AAV2/5.EFEMP1wt and AAV2/5 EFEMP1mut encode epidermal growth factor containing fibrillin-like extracellular matrix protein wild-type and mutant R345W, where an arginine codon is substituted for a tryptophan codon. In patients with Malattia Leventinese (ML), an autosomal dominant macular degenerative disease, the EFEMP1 protein has been shown to accumulate within RPE cells and between the RPE and drusen. In vitro studies have shown that the EFEMP1wt protein is secreted while the EFEMP1mut protein is misfolded, poorly secreted and retained within cells. These results suggest that a misfolding and aberrant accumulation of EFEMP protein may underlie drusen formation and other abnormalities in the retinas of patients with ML and AMD. Initial analysis of the DIGE data shows the presence of both downregulated and upregulated proteins. Analysis of the microarray data shows the downregulation of a number of cell cycle regulator, DNA replication, kinase, kinesin-like (motor), and survivin [baculoviral IAP (apoptosis inhibitor protein) repeat-containing 5 and survivin-beta] genes for rAAV infected cells compared with uninfected RPE cells. Interestingly, there appears to be very little or no change in immune response, inflammatory response or signal transduction genes. Additional proteomic studies using DIGE and SILAC (stable isotope labeling with amino acids in cell culture) as well as continuing microarray studies are in progress to provide further understanding of the effect on the proteome and genome of these important gene therapy tools for the treatment of inherited retinal diseases.
The Smokeless Pipe
Authors: D. Malcolm
Journal: JAMA (1970)

To the Editor. —  Dr. Friederici's statement about the complexity of the mechanisms of pleasure in smoking reminded me of how startled I was to find that I was unable to appreciate the sensations of cigarette smoke inhalation while smoking in a dark room. Visual clues must be important in smoking pleasure; I suspect the perception of the presence of the smoke itself is the important factor.
First Line Chemotherapy with Weekly Docetaxel and Cisplatin in Elderly Patients with Advanced Non-small Cell Lung Cancer: A Multicenter Phase II Study
Authors: Keqi Han, Weiguo Cao, Jinfeng Che, Shenxu Bo, Xiaodong Guo, Guang Huang, Lijun Ma, Liangqi Sun, Chunfang Gao, Baoliang Zhong, Zhigang Cao, Steven Jay Tucker, Daoyuan Wang
Journal: Journal of Thoracic Oncology (2009)
The state and the profession: the politics of the double bed.
Authors: R Klein
Journal: BMJ (1990)

permission of the, estate of EHShepard) In retrospect it is clear that those who fought Nye Bevan's plans for setting up the National Health Service were right in at least one important respect. The setting up in 1948 marked a revolution in the relation between the state and the medical profession. But it was not quite the revolution that the critics had anticipated and prophesied. It did not mean the triumph of bureaucracy over professionalism or the subordination of doctoring to ministerial diktat. Instead, it created a situation of mutual dependency. On the one hand the state became a monopoly employer: effectively members of the medical profes? sion became dependent on it not only for their own incomes but also for the resources at their command. On the other hand the state became dependent on the medical profession to run the NHS and to cope with the problems of rationing scarce resources in patient care. The subsequent history of the NHS can, in institutional and political terms, be seen largely as a series of attempts to manage this mutual dependency, to find ways of accommodating the frustrations and resentments of both sides in the partnership, and to devise organisational strategies for containing con? flicting interests within the framework of the NHS. My theme, in short, is that it is possible to understand what is happening in the NHS today?and indeed what has happened over the past 40 odd years?only if it is seen
P275 THE NUCLEAR RECEPTOR LRH-1 IS A KEY REGULATOR OF THE HEPATIC METHYL-POOL AND PHOSPHATIDYLCHOLINE METABOLISM
Authors: M. Wagner, J.L. Mamrosh, R. Wooton-Kee, J.M. Lee, R. Xiao, N. Putluri, M. Stahlman, J. Boren, A. Sreekumar, D.D. Moore
Journal: Journal of Hepatology (2014)
HIV Epidemiology in Africa: Weak Variables and Tendentiousness Generate Wobbly Conclusions
Authors: Stuart Brody, John J Potterat
Journal: PLoS Medicine (2005)

I previously criticised the effective "statute of limitations" in several leading general medical journals "whereby authors of papers are immune to disclosure of methodological weaknesses once some arbitrary (short) period has elapsed" [2].Such a time limit discourages post-publication peer review, with potential correspondents deterred by the short and unambiguous deadline.I suggested that journals with such a policy should reconsider.The word limit on that article precluded additional adverse comments on journals' word limits for letters, although they were presented in Table 2 of that article [2].Subsequently, three of the six journals did revise their instructions [3-5], but each imposed tougher restrictions on letters, reducing either the maximum time limit, the maximum length, or both.The strictest current requirements are a two-week limit by The Lancet and a 175-word limit by the New England Journal of Medicine.Editors are seemingly falling over themselves to speed up and shorten letters, but this behaviour is inappropriate for a scientifi c journal.The key characteristic of science is not its infallibility, a quality it clearly does not and cannot have, but its self-correcting ability.The decision by medical editors to stifl e debate is misguided [2,6].A time limit, especially a very short one, signals that speed is more important than content, that convenience takes precedence over science.While it is reasonable to encourage early comments, there should be no time limit on comments aimed at clarifying or criticising study methodology.Likewise, it will often be impossible to explain the subtleties of methodological problems in 400 words, and impossible in only 175.Additional restrictions on the number of authors and references are also questionable.I am disappointed that PLoS Medicine has imposed a time limit of four weeks on correspondence.As explained above, I believe that such a limit is mistaken.
Tumor of Undescended Testicle in an Infant
Authors: Joseph L. Hansen
Journal: JAMA (1967)

A TERATOMA in the undescended testis of an infant is of such rarity that a search of the American literature published during the past ten years fails to show a reported case. I have no knowledge of any other reports. The following case report is rendered for that reason and with the hope that it may be of interest to those dealing with patients of similar age and sex, for teratoma is another lesion to be considered in the differential diagnosis of an intra-abdominal mass in an infant. Teratomas are neoplasms arising from totipotential cells that produce many types of tissue. They are most frequently found in the gonads but occur at times in the neck and mediastinum. They may become malignant. One can postulate that the presence of a tumor in an undescended testis indicates that its size may have prevented descent of the embryonic organ. This migration takes
A phase II randomized vehicle-controlled trial of intradermal allogeneic fibroblasts for recessive dystrophic epidermolysis bullosa
Authors: Supriya S. Venugopal, Wenfei Yan, John W. Frew, Heather I. Cohn, Lesley M. Rhodes, Kim Tran, Wei Melbourne, Janis A. Nelson, Marian Sturm, Janice Fogarty, M. Peter Marinkovich, Satomi Igawa, Akemi Ishida-Yamamoto, Dedee F. Murrell
Journal: Journal of the American Academy of Dermatology (2013)
Identification of Metabolites of Trenbolone Acetate in Androgenic Runoff from a Beef Feedlot
Authors: Elizabeth J. Durhan, Christy S. Lambright, Elizabeth A. Makynen, James Lazorchak, Phillip C. Hartig, Vickie S. Wilson, L. Earl Gray, Gerald T. Ankley
Journal: Environmental Health Perspectives (2005)

Little is known concerning the potential ecological effects of hormonally active substances associated with discharges from animal feeding operations. Trenbolone acetate is a synthetic anabolic steroid that is widely used in the United States to promote growth of beef cattle. Metabolites of trenbolone acetate include the stereoisomers 17α- and 17β-trenbolone, both of which are stable in animal wastes and are relatively potent androgens in fish and mammals. Our purpose in this study was to evaluate the occurrence of 17α- and 17β-trenbolone in a beef cattle feedlot discharge and in river water upstream and downstream from the discharge. In conjunction with that effort, we measured in vitro androgenic activity of the discharge using CV-1 cells that had been transiently cotransfected with human androgen receptor and reporter gene constructs. Samples were collected on nine different occasions during 2002 and 2003. Whole-water samples from the discharge caused a significant androgenic response in the CV-1 cells and contained detectable concentrations of 17α- and 17β-trenbolone. Further work is needed to ascertain the degree to which synthetic androgens such as trenbolone contribute to androgenic activity of feedlot discharges.
TCT-674 WATCHMAN Left Atrial Appendage Occluder In Octogenarians: Short-term And One-year Follow-up
Authors: Sameer Gafoor, Jennifer Franke, Stefan C. Bertog, Patrick Boehm, Maik Gonzaga, Janine Bauer, Annkathrin Braut, Simon C.C. Lam, Laura Vaskelyte, Ilona Hofmann, Horst Sievert
Journal: Journal of the American College of Cardiology (2013)
Gas-Producing Escherichia coli Fasciitis in a Patient With the Neuroleptic Malignant Syndrome
Authors: Charles B. Sherman
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The neuroleptic malignant syndrome (NMS) is an uncommon but potentially fatal reaction to major tranquilizers. It is characterized by hyperpyrexia, muscle rigidity, altered consciousness, and autonomicdysfunction.<sup>1,2</sup>We report a dramatic case of the NMS complicated by bilateral anterior tibial compartment syndromes that were infected by gasproducing<i>Escherichia coli</i>. <h3>Report of a Case.—</h3> A 29-year-old man was admitted to the Bernalillo County Mental Health Center, Albuquerque, with the diagnosis of acute paranoid schizophrenia. During a 12-hour period, he received 90 mg of haloperidol and 100 mg of chlorpromazine orally. Two hours later, he was comatose, hypotensive, hyperpyrexic (rectal temperature, 41.3 °C), and rigid, with clonic jerking movements, and was transferred to the University of New Mexico Hospital, Albuquerque. His creatine kinase level was 220,000 IU/L, his uric acid level was 25.2 mg/mL, and the scanty urine specimens were positive for myoglobin and initially yellow and then burgundy-colored
Evidence debased medicine
Authors: T. Groves
Journal: BMJ (2010)

Our current evidence base on the benefits and harms of many treatments contains incomplete and questionable evidence. This week Elizabeth Loder and Fiona Godlee call for the record to be set straight and announce a BMJ theme issue in late 2011 for research that analyses uncovered evidence (doi:10.1136/bmj.c5641). The aim is to restore trust in the evidence base, not to point fingers.

This is an early call, but such studies take time because they often depend on freedom of information requests and protracted negotiations with companies. Dirk Eyding, Beate Wieseler, and colleagues from the German Institute for Quality and Efficiency in …
Some reflections on sex differences in aggression and violence
Authors: Stephen C. Maxson
Journal: Behavioral and Brain Sciences (1999)

Four issues relevant to sex differences in human aggression and violence are considered. (1) The motivation for play and serious aggression in children and juvenile animals is different. Consequently, the evolutionary explanations for each may be different. (2) Sex differences in intrasexual aggression may be due to effects of the attacker or the target. There is evidence that both males and females are more physically aggressive against males and less physically aggressive against females. The evolutionary explanation for each component of the sex difference in intrasexual aggression may be different. (3) Aggression and violence are defined. The former is the attack, and the latter is the consequent injury or death. The evolutionary explanation for each may not be the same. (4) Most men and women are neither physically aggressive nor criminally violent. The evolutionary explanations of sex differences in aggression and violence should take this polymorphism into account.
"It's Only a Phase"
Authors: Robert J. Stoller
Journal: JAMA (1967)

In our society today, with its present style in younger people of blurring the outward manifestations of sexual differences, many people, including physicians, are uncertain when, in children, cross-gender behavior is significant and when it is only transient experimental play with no importance for future gender or sexual behavior. This commentary is concerned with boys about whom the statement is made, "It's only a phase," when they are found dressing in girls' or women's clothes. The child's parents sometimes repeat this phrase for years and will describe how school authorities, physicians, neighbors, and anyone else with whom they discuss their boy's femininity almost always minimize the cross-gender behavior, permitting it to persist by saying that it will disappear in time. Not only that, these people quite frequently and correctly cite cases they have known of little boys who in some way behaved in a feminine or effeminate way and still
Mitoxantrone, etoposide, cytarabine, and melphalan (NEAM) followed by autologous stem cell transplantation for patients with chemosensitive aggressive non‐Hodgkin lymphoma
Authors: Ji‐Won Kim, Hyun Jung Lee, Hyeon Gyu Yi, Byung‐Su Kim, Soo‐Mee Bang, Jin Seok Kim, Inho Kim, Sung‐Soo Yoon, Jong Seok Lee, Chul Soo Kim, Seonyang Park, Byoung Kook Kim
Journal: American Journal of Hematology (2012)

Patients with chemosensitive aggressive non-Hodgkin lymphoma (NHL) could benefit from high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (auto-SCT). We report clinical outcomes of HDC using a novel regimen consisting of mitoxantrone, etoposide, cytarabine, and melphalan (NEAM) with auto-SCT. A total of 69 patients were consecutively enrolled. Median age was 42 years (range, 20-66 years). Median event-free survival (EFS) was 17.9 months. Median overall survival (OS) has not been reached yet and estimated 2-year OS was 64.2%. Among patients with measurable lesions, response rate was 79.5%. Median time to recovery of neutrophil (>500 mL) and platelet (gt;20,000 mL) was 12.5 and 13.5 days, respectively. Febrile neutropenia developed in 61 patients (88.4%). Grades 3 or 4 hepatic toxicity developed in 7 patients (10.1%), Grades 3 or 4 renal toxicity in 2 patients (2.9%), and Grade 3 or 4 cardiac toxicity in 2 patients (2.9%). Transplant-related mortality (TRM) developed in two patients (2.9%). Multiple prior treatments before transplantation, auxiliary bone marrow harvest for stem cell collection, and high serum lactate dehydrogenase level were related to unfavorable treatment outcomes. In conclusion, NEAM conditioning with auto-SCT demonstrated considerable efficacy with modest toxicity in patients with chemosensitive aggressive NHL.