tbuckley/cabot-search huggingface dataset:
Drug fever due to oxprenolol.
Authors: K Hasegawa, Y Sakamoto, K Mitsunaga, H Kashiwagi
Journal: BMJ (1980)

<h3>Abstract</h3> <h3>Background</h3> Little is known about the dynamics of SARS-CoV-2 antigen burden in respiratory samples in different patient populations at different stages of infection. Current rapid antigen tests cannot quantitate and track antigen dynamics with high sensitivity and specificity in respiratory samples. <h3>Methods</h3> We developed and validated an ultra-sensitive SARS-CoV-2 antigen assay with smartphone readout using the Microbubbling Digital Assay previously developed by our group, which is a platform that enables highly sensitive detection and quantitation of protein biomarkers. A computer vision-based algorithm was developed for microbubble smartphone image recognition and quantitation. A machine learning-based classifier was developed to classify the smartphone images based on detected microbubbles. Using this assay, we tracked antigen dynamics in serial swab samples from COVID patients hospitalized in ICU and immunocompromised COVID patients. <h3>Results</h3> The limit of detection (LOD) of the Microbubbling SARS-CoV-2 Antigen Assay was 0.5 pg/mL (10.6 fM) recombinant nucleocapsid (N) antigen or 4000 copies/mL inactivated SARS-CoV-2 virus in nasopharyngeal (NP) swabs, comparable to many rRT-PCR methods. The assay had high analytical specificity towards SARS-CoV-2. Compared to EUA-approved rRT-PCR methods, the Microbubbling Antigen Assay demonstrated a positive percent agreement (PPA) of 97% (95% confidence interval (CI), 92-99%) in symptomatic individuals within 7 days of symptom onset and positive SARS-CoV-2 nucleic acid results, and a negative percent agreement (NPA) of 97% (95% CI, 94-100%) in symptomatic and asymptomatic individuals with negative nucleic acid results. Antigen positivity rate in NP swabs gradually decreased as days-after-symptom-onset increased, despite persistent nucleic acid positivity of the same samples. The computer vision and machine learning-based automatic microbubble image classifier could accurately identify positives and negatives, based on microbubble counts and sizes. Total microbubble volume, a potential marker of antigen burden, correlated inversely with Ct values and days-after-symptom-onset. Antigen was detected for longer periods of time in immunocompromised patients with hematologic malignancies, compared to immunocompetent individuals. Simultaneous detectable antigens and nucleic acids may indicate the presence of replicating viruses in patients with persistent infections. <h3>Conclusions</h3> The Microbubbling SARS-CoV-2 Antigen Assay enables sensitive and specific detection of acute infections, and quantitation and tracking of antigen dynamics in different patient populations at various stages of infection. With smartphone compatibility and automated image processing, the assay is well-positioned to be adapted for point-of-care diagnosis and to explore the clinical implications of antigen dynamics in future studies.
Review: In adult outpatients, nurse-managed protocols improve hemoglobin A<sub>1c</sub>levels and blood pressure
Authors: Kevin A. Schulman
Journal: Annals of Internal Medicine (2014)

Source Citation Shaw RJ, McDuffie JR, Hendrix CC, et al. Effects of nurse-managed protocols in the outpatient management of adults with chronic conditions: a systematic review and meta-analysis. Ann Intern Med. 2014;161:113-21. 25023250
278LQT5 transgenic rabbits are characterized by increased repolarization instability and arrhythmia susceptibility
Authors: I Baczko, V Juhasz, P Major, M Kovacs, T Hornyik, A Kerekes, L Hiripi, ZS Bosze, JGY Papp, A Varro
Journal: Cardiovascular Research (2014)

Purpose: Despite the existence of some in vivo animal proarrhythmia models, the reliable prediction of the proarrhythmic risk associated with novel compounds under development remains unsatisfactory. Therefore, new models with better predictive value for proarrhythmic risk assessment are needed. In this study, we carried out the primary characterization of a new transgenic LQT5 rabbit model recently generated by our group based on the selective overexpression of mutant human KCNE1 gene in the heart. The missense mutation was first identified in a Chinese LQT syndrome family. Methods: The proarrhythmic susceptibility of LQT5 transgenic rabbits was evaluated by administration of the IKr blocker dofetilide (20 μg/kg). In thiopental anesthetized transgenic (TG; n=26) and wild type rabbits (WT; n=27), the ECG was continuously registered using a specialized computer software before, during and following the infusion of dofetilide, and arrhythmia development was also monitored. ECG recordings were evaluated off-line. Results: Conventional ECG parameters characterizing repolarization duration, the QT and frequency corrected QT intervals (QTc), were not different in the two groups at baseline (QT: 146.9 ± 3.18 in WT vs. 145.7 ± 2.87 ms in TG; QTc: 156.8 ± 2.63 in WT vs. 155.6 ± 2.12 ms in TG, all p>0.05). Following the administration of dofetilide, QT and QTc intervals were significantly prolonged in both groups to a similar extent (QTc: 169.4 ± 3.37 in WT and 167.8 ± 3.17 ms in TG). However, the short-term variability of the QT interval, a novel ECG parameter suggested for the better estimation of repolarization temporal instability and proarrhythmic risk, was higher in KCNE1 transgenic rabbits compared to wild type at baseline (4.8 ± 0.26 in TG vs. 2.8 ± 0.15 ms in WT, p<0.05). Following the administration of dofetilide, the incidence of the typically drug induced Torsades des Pointes arrhythmia was significantly higher in transgenic rabbits compared to wild type (77% in TG vs. 51.8% in WT, p<0.05). Conclusions: Our results suggest that KCNE1 transgenic LQT5 rabbits have high susceptibility to drug induced arrhythmias and may represent a model suitable for the more reliable testing of the proarrhythmic potential of new compounds under development.
CONDITIONS IN THE INDIAN MEDICAL SERVICE
Authors: Hubert Work
Journal: JAMA (1923)

<h3>[Note.</h3> —The letter by Dr. Benson, and the one by Dr. J. H. Darey published last week, were referred in proof to Dr. Hubert Work, Secretary of the Interior, who replies:] <h3>To the Editor:</h3> —I have read with interest the communications in proof form entitled "Conditions in the Indian Medical Service," by Dr. Otis O. Benson of Floodwood, Minn., and by Dr. J. Herbert Darey of Sioux City, Iowa, and am pleased that the physicians are directing thought toward the activity of the government's dealing with human welfare. In staccato form, to insure brevity: There are approximately 340,000 Indians in the United States, an increase of 13,500 during the last ten years. Over 100,000 Indians have been removed entirely from the jurisdiction of the Interior Department, so far as their individual property rights may be concerned, but some of these Indians still retain an interest in undistributed tribal property. The
SARS transmission: language and droplet production
Authors: Sakae Inouye
Journal: The Lancet (2003)

Severe acute respiratory syndrome (SARS) is transmitted via droplets spread by infected individuals. Droplets are generated when patients cough and, to a lesser extent, when they talk during the early stages of disease. I believe that the efficiency of transmission of SARS by talking might be affected by the language spoken. As of mid June, 2003, the number of probable cases of SARS in Japan remained zero, whereas there were more than 70 cases diagnosed in the USA.1WHOCumulative number of reported probable cases of SARS.http://www.who.int/csr/sars/country/2003_06_18/en/Google Scholar There were about 3·1 million Japanese travellers to mainland China, Hong Kong, and Taiwan in 2000,2Minister's Secretariat.Annual report of statistics on legal migrants. Ministry of Justice, Tokyo2001Google Scholar and about 2·3 million US citizens visited these areas in 2001.3ITA Office of Travel and Tourism Industries2001 profile of US resident traveler visiting overseas destinations reported from: survey of international air travelers.http://tinet.ita.doc.gov/view/f-2001-101-001/index.html?ti_cart_cookie=20030Google Scholar With such large numbers of visitors from Japan and USA, why have no Japanese visitors contracted the virus? Here, I propose a hypothesis. The Chinese language has an aspiration/non-aspiration pronunciation system: the consonants p, t, k, q, ch, and c, when placed in front of vowels, are pronounced with a strong breath, by contrast with b, d, g, j, zh, and z. In English, but not in Japanese, p, t, and k are pronounced with a similar accompanying exhalation of breath. Furthermore, the p sound is not used as frequently in Japanese as in English. Aspiration could produce droplets. A Chinese attendant in a souvenir shop probably speaks to American tourists in English, and to Japanese tourists in Japanese. If the shop assistant is in the early stages of SARS and has no cough, I believe American tourists would, hence, be exposed to the infectious droplets to a greater extent than would Japanese tourists. I thank Professors S Yabuki, Yokohama City University, and T Kohno, Otsuma Women's University, for discussions on cultural and linguistic aspects of Chinese and American people.
ELLIPTICAL LEFT VENTRICULAR OUTFLOW TRACT IN PATIENTS WITH CALCIFIC AORTIC STENOSIS: IMPLICATIONS FOR ECHOCARDIOGRAPHIC CONTINUITY EQUATION AND ASSESSMENT OF DISEASE SEVERITY
Authors: Bridget O'Brien, Paul Schoenhagen, Samir R. Kapadia, Lars G. Svensson, L. Leonardo Rodriguez, Brian P. Griffin, E. Murat Tuzcu, Milind Y. Desai
Journal: Journal of the American College of Cardiology (2011)
Haemolysis in experimental cholestasis: Possible role of erythrocyte sialic acid
Authors: L. W. Powell, J. T. Lamont, K. J. Isselbacher
Journal: Gut (1974)

Because previous studies have suggested that red cell membrane sialic acid might be a determinant of survival <i>in vivo</i>, we examined the relationship between haemolysis, erythrocyte membrane sialic acid, and hepatic neuraminidase (sialidase) levels in experimental cholestatic jaundice in rats. Treatment of normal rat erythrocytes with neuraminidase <i>in vitro</i> resulted in a significant reduction in their survival <i>in vivo</i> and removal by the spleen. The degree of haemolysis was comparable to that previously found 12 days after bile duct ligation in rats. Bile duct ligation resulted in a significant increase in hepatic neuraminidase and a decrease in erythrocyte sialic acid. The findings are consistent with the hypothesis that one or more neuraminidases present in inreased amounts in the bile duct-ligated livers are responsible for the removal of sialic acid from circulating erythrocytes and subsequent removal of these cells in the spleen.
Controlled trial of long term oral potassium supplements in patients with mild hypertension.
Authors: A Siani, P Strazzullo, L Russo, S Guglielmi, L Iacoviello, L A Ferrara, M Mancini
Journal: BMJ (1987)

A 15 week randomised double blind placebo controlled trial of oral potassium supplements (48 mmol daily) was conducted in 37 patients who had mildly increased blood pressure and a normal dietary intake of sodium. After a two month run in and a one week baseline period the patients were randomly assigned to receive either potassium supplements (n = 18) or placebo (n = 19). By the third week of treatment blood pressure in the actively treated group had decreased significantly compared with that in the placebo group, though the decrease reached its maximum after 15 weeks. Urinary potassium excretion increased significantly in the group who received potassium supplements, but no significant changes were found in plasma sodium and potassium concentrations or in urinary sodium excretion. In a subgroup of 13 patients who underwent a further nine weeks of treatment with oral potassium supplements at half of the previous dose (24 mmol daily) their blood pressure, at the end of this second study period, was still significantly lower compared with their baseline value but not with that of the placebo group. These results show that moderate oral potassium supplements are associated with a long term reduction in blood pressure in patients who have mild hypertension.
Receptor-targeted Nanocomplexes optimized for Gene Transfer to Primary Vascular Cells and Explant Cultures of Rabbit Aorta
Authors: Scott A Irvine, Qing-Hai Meng, Faiza Afzal, Jimmy Ho, John B Wong, Helen C Hailes, Alethea B Tabor, Jean R McEwan, Stephen L Hart
Journal: Molecular Therapy (2008)

We have developed new, synthetic vector formulations that display high efficiency of gene transfer to vascular cells and tissues. The formulations comprise cationic liposomes and cationic, receptor-targeting peptides that self assemble on mixing with plasmid DNA into receptor-targeted nanocomplexes (RTNs). One such RTN formulation was optimal for transfection of primary smooth muscle cells (LYD-1), while a second was optimal for transfection of rabbit aortic explants (LYD-2). In both RTNs, the peptide was a 16-lysine motif linked to the targeting sequence CYGLPHKFCG via a short spacer sequence. The major difference between LYD-1 and LYD-2 lay in the cationic lipid component, where LYD-1 contained ditetradecyl trimethyl ammonium (DTDTMA), an unsaturated, cationic lipid with a 14-carbon alkyl tail, whereas LYD-2 contained 2,3-dioleyloxypropyl-1-trimethyl ammonium chloride (DOTMA), a cationic lipid with an 18-carbon unsaturated alkyl tail. LYD-2 transfections of aortic explants were effective with incubations performed at room temperature for as little as 30 minutes, with either saline or glucose-based solutions. Transgene expression in the explants peaked at 5 days and persisted for 14 days. The kinetics of transfected gene expression, along with the efficacy of transfection with short incubation times, indicate that these new formulations may be useful tools in the development of molecular therapies for cardiovascular diseases. We have developed new, synthetic vector formulations that display high efficiency of gene transfer to vascular cells and tissues. The formulations comprise cationic liposomes and cationic, receptor-targeting peptides that self assemble on mixing with plasmid DNA into receptor-targeted nanocomplexes (RTNs). One such RTN formulation was optimal for transfection of primary smooth muscle cells (LYD-1), while a second was optimal for transfection of rabbit aortic explants (LYD-2). In both RTNs, the peptide was a 16-lysine motif linked to the targeting sequence CYGLPHKFCG via a short spacer sequence. The major difference between LYD-1 and LYD-2 lay in the cationic lipid component, where LYD-1 contained ditetradecyl trimethyl ammonium (DTDTMA), an unsaturated, cationic lipid with a 14-carbon alkyl tail, whereas LYD-2 contained 2,3-dioleyloxypropyl-1-trimethyl ammonium chloride (DOTMA), a cationic lipid with an 18-carbon unsaturated alkyl tail. LYD-2 transfections of aortic explants were effective with incubations performed at room temperature for as little as 30 minutes, with either saline or glucose-based solutions. Transgene expression in the explants peaked at 5 days and persisted for 14 days. The kinetics of transfected gene expression, along with the efficacy of transfection with short incubation times, indicate that these new formulations may be useful tools in the development of molecular therapies for cardiovascular diseases.
Amitriptyline and Fluphenazine for Painful Diabetic Neuropathy-Reply
Authors: Carl M. Mendel
Journal: JAMA (1986)

<h3>In Reply.—</h3> Our study demonstrated that patients with painful diabetic neuropathy experience pain relief when treated with placebos, and, after a review of the literature, we concluded that no valid objective data exist that support the view that amitriptyline and fluphenazine are any more effective than placebos in treatment of this condition and cautioned against their inappropriate use. Another study using pyridoxine as the active drug also found a placebo response in patients with painful diabetic neuropathy and reached similar conclusions.<sup>1</sup> We were interested to hear of Dr Ritter's success with amitriptyline and fluphenazine in treating his own spinal arachnoiditis, but that does not bear directly on our study, which was designed in the context of previous uncontrolled studies on painful diabetic neuropathy (cited in our article). These studies described pain relief within one to several days following initiation of therapy with amitriptyline and fluphenazine and resumption of pain
Exhaled nitric oxide and inhaled corticosteroid dose reduction in asthma: a cohort study
Authors: Emma Wilson, Tricia McKeever, Beverley Hargadon, Glenn Hearson, John Anderson, David Hodgson, Helen Bailey, Garry Meakin, Mike Thomas, Ian D. Pavord, Tim Harrison, Dominick Shaw
Journal: European Respiratory Journal (2014)

Nitric oxide and inhaled
Defending the indefensible
Authors: D. Spence
Journal: BMJ (2009)

I lashed two pens together to write my 500 lines: “I must not swear in the corridor.” I accepted my punishment, for I had indeed been swearing loudly and repeatedly. My school wasn’t “flipping” Grange Hill. The British are superficially a polite people, renowned the world over for apologising for things that they didn’t do nor were responsible for. But this is a mere veneer, for underlying our “Terribly sorry” we are sarcastic and rude and, from Shetland to Land’s End, given …
East meets West: an herbal tea finds a receptor
Authors: Mitchell A. Lazar
Journal: Journal of Clinical Investigation (2004)

Jaundice, which is caused by accumulation of bilirubin, is extremely common in newborn infants. Phototherapy is an effective treatment, but a drug therapy would also be desirable. A Chinese herbal remedy for jaundice called Yin Zhi Huang is now shown to activate a liver receptor that enhances the clearance of bilirubin (see the related article beginning on page 137). This discovery could lead to improved pharmaceutical treatments for neonatal jaundice.
Multiple Brain Abscesses
Authors: M Igarashi
Journal: New England Journal of Medicine (1993)

Figure 1. Multiple Brain Abscesses. Both images are computed tomographic scans (with contrast) of the head of an eight-year-old boy with a 10-day history of headaches, vomiting, fever, altered mental status, and frontal-lobe signs. More than 30 ring-enhancing lesions are present. The precontrast study showed only one low-density lesion in the left thalamus. The abscesses resolved completely after antibiotic therapy, although the left thalamic lesion grew larger during the first 10 days. Initially, treatment consisted of nafcillin and chloramphenicol; nafcillin was replaced by penicillin G after one week. Extensive studies failed to uncover the source or type of infection.
Drug companies pay out millions after overcharging Medicaid
Authors: O. Dyer
Journal: BMJ (2003)

The German pharmaceutical giant Bayer is to plead guilty to criminal charges and pay $257m (£165m; €236m) in fines and civil damages for overcharging Medicaid, the US state and federally funded health insurance plan for patients with low income aged under 65 years. US prosecutors have called the case the biggest Medicaid fraud recovery in the country's history.

The British drug company GlaxoSmithKline will pay out $87.6m to settle a similar case.

Both companies were accused of breaching rules which demand that companies participating in Medicaid offer the programme the lowest available prices for their drugs. Instead, …
Training and careers of women doctors
Authors: B. Beaumont
Journal: BMJ (1978)

SIR,-The usable response rate of 75 °in this survey compares favourably with results from other surveys using the Medical Register or Medical Directory as a sampling frame.As stated in my report (21 January, p 191), doctors qualified in the UK were more likely to respond than those elsewhere, as were doctors who qualified before 1960.As with any published results, it is up to the reader to form his or her own opinion whether valid conclusions can be drawn in the light of stated sampling bias and statistically significant findings.For reasons of space, a detailed analysis of reasons for non-response was not included in the survey report, but is given here: Questionnaires returned marked "gone away" 171 Questionnaires returned blank (refusal) .. 28Questionnaires not returned . .611Ten per cent of those in the third group were telephoned, and reasons for non-response were:Moved from registered address .40,
Childhood History of Resolved Glomerular Disease and Risk of Hypertension During Adulthood
Authors: Asaf Vivante, Gilad Twig, Amir Tirosh, Karl Skorecki, Ronit Calderon-Margalit
Journal: JAMA (2014)

Most children who develop glomerular disease have a favorable prognosis with complete resolution of all signs and symptoms. Yet the long-term sequelae of resolved childhood glomerular disease are incompletely understood. We assessed whether a medical history of resolved childhood glomerular disease confers a future risk for hypertension.
Plugging gaps in China's hepatitis B prevention would be cost effective
Authors: J. Parry
Journal: BMJ (2009)

A country-wide catch-up hepatitis B vaccination programme in China would save thousands of lives and be cost effective, research from Stanford University has shown ( Hepatology 2009 Sep 9, doi:10.1002/hep.23310).

Vaccinating the estimated 150 million children aged 1-19 years who are currently unprotected will cost an estimated $423m (£260m; €281m) but will save the economy $840m, by preventing eight million infections and 65 000 deaths, the researchers found.

Routine free vaccination of babies against the disease began only in 2002, and serological survey data show that 40% of children …
The Genetic Basis of Type 2 Diabetes Mellitus: Impaired Insulin Secretion versus Impaired Insulin Sensitivity
Authors: John E. Gerich
Journal: Endocrine Reviews (1998)

Despite the fact that it is the prevalent view that insulin resistance is the main genetic factor predisposing to development of type 2 diabetes, review of several lines of evidence in the literature indicates a lack of overwhelming support for this concept. In fact, the literature better supports the case of impaired insulin secretion being the initial and main genetic factor predisposing to type 2 diabetes, especially 1) the studies in people at high risk to subsequently develop type 2 diabetes (discordant monozygotic twins and women with previous gestational diabetes), 2) the studies demonstrating compete alleviation of insulin resistance with weight loss, and 3) the studies finding that people with type 2 diabetes or IGT can have impaired insulin secretion and no insulin resistance compared with well matched NGT subjects. The fact that insulin resistance may be largely an acquired problem in no way lessens its importance in the pathogenesis of type 2 diabetes. Life style changes (exercise, weight reduction) and pharmacological agents (e.g., biguanides and thiazolidendiones) that reduce insulin resistance or increase insulin sensitivity clearly have major beneficial effects (122, 144-146, 153-155).