tbuckley/cabot-search huggingface dataset:
Bidirectional transport of glutathione in hepatocyte membranes: Does glutathione efflux stimulate organic anion uptake?
Authors: Ned Ballatori
Journal: Hepatology (1993)

We determined the trans effects of extracellular reduced glutathione (GSH) on the rate of efflux of endogenous labeled GSH from freshly isolated rat hepatocytes. The presence of GSH (10 mM) in the medium significantly stimulated the fractional rate of efflux of [ 35 S]GSH from 5.2 to 12.6%/15 min ( p &lt; 0.01). This effect was concentration-dependent, had sigmoid type of kinetics (D 50 of 0.32 mM), and was reversible upon removal of external GSH. trans -Stimulation (counter-transport) was also observed with 5 mM oxidized glutathione (GSSG) and ophthalmic acid (fractional [ 35 S]GSH efflux: 13.4% ± 4.1 and 8.8% ± 2.3 in 15 min, respectively, compared with control: 4.7 ± 2.5/15 min). Bromosulphthalein-glutathione (BSP-GSH, 5 mM) in Krebs buffer inhibited the fractional [ 35 S]GSH efflux (1.1%/15 min), whereas in Cl −- -free buffer, GSH efflux was stimulated (14.2%/15 min) compared with control. trans -Stimulation was independent of chloride. BSP-GSH cis -inhibited and trans -stimulated the initial rate of GSH transport in basolateral-enriched membrane vesicles (bLPM) but not in canalicular-enriched membrane vesicles (cLPM). γ-Glutamyl compounds also cis -inhibited and trans -stimulated GSH transport in bLPM vesicles. GSH-depleted hepatocytes incubated with 10 mM [ 35 S]GSH accumulated more GSH than repleted cells, but the initial rate of uptake of radioactivity was faster in repleted cells. In contrast, repleted hepatocytes incubated with tracer or 50 μM [ 35 S]GSH did not take up GSH. Thus, the sinusoidal membrane GSH transporter exhibits low affinity kinetics with sigmoid features for both GSH uptake and trans -stimulation of efflux, explaining the lack of uptake of GSH at low physiologic extracellular concentrations. Therefore, our findings support and explain the widely held view that GSH transport is unidirectional under physiologic conditions. However, the efflux of GSH may also occur in exchange for the uptake of organic anions and γ-glutamyl compounds. (J Biol Chem 1992;267:22256-22264.)
Better access to drugs could save 10 million lives a year, says UN expert
Authors: John Zarocostas
Journal: BMJ (2007)

Better access to drugs, especially in poor countries, could save 10 million lives each year, four million of them in Africa and South East Asia, an independent UN expert said as he unveiled a set of draft guidelines for pharmaceutical companies on access to drugs.

The 50 draft provisions drew a mixed response from interested parties. They were welcomed by groups that advocate for access to affordable drugs but were strongly criticised by the industry.

Announcing the guidelines, Paul Hunt, the United Nations' special rapporteur on the right of everyone to the enjoyment of the highest attainable standard of physical and mental health, said, “Almost two billion people lack access to essential medicines. Improving access to existing medicines could save 10 million …
Patch testing and prick testing: A practical guide by Jean-Marie Lachapelle and Howard I. Maibach; Management of positive patch test reactions by J. E. Wahlberg, P. Elsner, L. Kanerva, H. I. Maibach; Irritant dermatitis by Ai-Lean Chew and Howard I. Maibach; Condensed handbook of occupational dermatology by L. Kanerva, P. Elsner, J. E. Wahlberg, H. I. Maibach
Authors: Lionel Bercovitch
Journal: Journal of the American Academy of Dermatology (2007)
World leaders sign up to tackle causes of non-communicable diseases
Authors: R. Coombes
Journal: BMJ (2011)

<h3>ABSTRACT</h3> <h3>Background</h3> Probiotics have been proposed as adjuvants for Coronavirus Disease 2019 (Covid19) but randomized controlled trials (RCT) are lacking. <h3>Methods</h3> Single-center, quadruple-blinded RCT. Symptomatic Covid 19 outpatients (aged 18 to 60 years) with positive SARS-CoV2 nucleic acids test were randomized to active (n=150; ≥2×10<sup>9</sup> colony-forming units (CFU) of probiotic strains <i>Lactiplantibacillus plantarum</i> KABP022, KABP023 and KAPB033, plus strain <i>Pediococcus acidilactici</i> KABP021) or placebo (n=150), take orally once daily for 30 days. Oral acetaminophen was allowed and controlled as co-intervention. Primary endpoint included: i) proportion of patients in complete remission (both symptoms and nucleic acids test) or progressing to moderate or severe disease with hospitalization; ii) death rate and duration on Intensive Care Unit (ICU). Safety was assessed in all patients. This study is registered at ClinicalTrials.gov (NCT04517422). <h3>Findings</h3> 300 subjects were randomized (median age 37.0 years [range 18 to 60], 161 [53.7%] women, 126 [42.0%] having known metabolic risk factors), and 293 completed the study (97.7%). Remission was achieved by 78 of 147 (53.1%) in the active group compared to 41 of 146 (28.1%) in placebo (P&lt;0.0001; ARR=25.0% [95%CI 14.1-35.9%]), still significant after multiplicity correction for the primary endpoint. No hospitalizations or deaths occurred during the study, precluding the assessment of efficacy on these endpoints. No serious adverse events occurred during the study. Replication studies with this probiotic formula are warranted.
The Medical Outcomes Study
Authors: Marcia A. Testa
Journal: JAMA (1996)

To the Editor.  —Dr Greenfield and colleagues 1 concluded that there were no meaningful differences in health outcomes for patients with hypertension or non—insulin-dependent diabetes mellitus (NIDDM) in the Medical Outcomes Study (MOS), whether their patients were treated by different systems of care or by different physician specialists. While the authors acknowledge the study's limitations regarding  circumstances and [n]o attempt... to equalize important variables, their conclusions seem inconsistent with the statistical implications of such limitations.  First, conclusions of equivalence or no meaningful differences require designs that can estimate with high statistical power the effects of systems of care and physician specialists independent of extraneous confounders such as age, severity of disease, and income. Because this was a nonrandomized observational study requiring extensive covariate adjustment, NIDDM comparison sample sizes of 77, 75, and 18 (Table 3) and 109,27, and 31 (Table 4) offer extremely low power, which practically guarantees that
Brain Repair after Stroke
Authors: Steven C. Cramer
Journal: New England Journal of Medicine (2010)

Stroke is the second leading cause of death worldwide. A majority of patients survive stroke, however, making this disorder a major source of human disability. Although most patients have some spontaneous behavioral improvements after a stroke, the recovery is generally incomplete. Compounding this burden of disability is the fact that one in four patients who have a stroke is under 65 years of age.An emerging approach to reducing the degree of disability after a stroke focuses on brain repair. Repair therapies aim to restore the brain, a goal that differs from that of neuroprotection therapies, in which the aim . . .
The Uses of Utilization Review
Authors: Steven Sieverts
Journal: New England Journal of Medicine (1978)

When patterns of medical care are analyzed, there are always so many things happening at once — and usually so many different ways of interpreting the same data — that we are well advised to step carefully when asked to infer that something is indubitably the result of something else.If phenomenon X has occurred during a period when program Y was under way, can we be certain that X was caused by Y? The pursuit of reasonable certainty in matters of this kind becomes crucial, of course, when program Y was conceived precisely to achieve medical-care phenomenon X, and . . .
Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function.
Authors: R A Daynes, B A Araneo, T A Dowell, K Huang, D Dudley
Journal: The Journal of Experimental Medicine (1990)

We investigated the capacity of murine T lymphocytes, isolated from various lymphoid organs of normal or antigen-primed donors, to produce IL-2 or IL-4 after activation with anti-CD3 or specific antigen. Our results established that T cells resident within lymphoid organs being drained by nonmucosal tissue sites (e.g., axillary, inguinal, brachial lymph nodes, or spleen) produced IL-2 as the predominant T cell growth factor (TCGF) after activation. Conversely, activated T cells from lymphoid organs being drained by mucosal tissues (Peyer's patches, and cervical, periaortic, and parathymic lymph nodes) produced IL-4 as the major species of TCGF. Analysis of the lymphoid tissues obtained from adoptive recipients of antigen-primed lymphocytes provided by syngeneic donors provided evidence that direct influences were being exerted on T cells during their residence within defined lymphoid compartments. These lymphoid tissue influences appeared to be responsible for altering the potential of resident T cells to produce distinct species of TCGF. Steroid hormones, known transcriptional enhancers and repressors of specific cellular genes, were implicated in the controlling mechanisms over TCGF production. Glucocorticoids (GCs) were found to exert a systemic effect on all recirculating T cells, evidenced by a marked dominance in IL-4 production by T cells obtained from all lymphoid organs of GC-treated mice, or after a direct exposure of normal lymphoid cells to GCs in vitro before cellular activation with T cell mitogens. Further, the androgen steroid DHEA appeared to be responsible for providing an epigenetic influence to T cells trafficking through peripheral lymphoid organs. This steroid influence resulted in an enhanced potential for IL-2 secretion after activation. Anatomic compartmentalization of the DHEA-facilitated influence appears to be mediated by differential levels of DHEA-sulfatase in lymphoid tissues. DHEA-sulfatase is an enzyme capable of converting DHEA-sulfate (inactive) to the active hormone DHEA. We find very high activities of this enzyme isolated in murine macrophages. The implications of our findings to immunobiology are very great, and indicate that T cells, while clonally restricted for antigen peptide recognition, also appear to exhibit an extreme flexibility with regards to the species of lymphokines they produce after activation. Regulation of this highly conservative mechanism appears to be partially, if not exclusively, controlled by cellular influences being exerted by distinct species of steroid hormones, supplied in an endocrine or a paracrine manner where they mediate either systemic or tissue-localized influences, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
HISTOLOGIC AND BACTERIOLOGIC NOTES ON THREE CASES OF PENETRATING WOUND OF THE EYEBALL, AND SOME OBSERVATIONS ON CERTAIN BACILLI FOUND IN A CASE OF POST-OPERATIVE PANOPHTHALMITIS.
Authors: G. E. De SCHWEINITZ
Journal: JAMA (1895)

In spite of numerous investigations, the exact nature of sympathetic ophthalmitis is not known, nor is the path of the morbid changes which precede the inflammation certainly ascertained, although the older hypotheses have largely been abandoned since 1881, and the disease ascribed to microbic origin. Three more or less distinct theories exist: The "Nerve-Irritation Theory" which, in a modified form, has been maintained by Schmidt-Rimpler thus: irritation of the ciliary nerves in the injured eye by means of disturbance in the circulation and nutrition, contrived in a reflex manner, is solely responsible for the disposition to sympathetic inflammation in the other eye. The longer the changes have existed and the more widespread they are, the better prepared is the soil for action of the inflammation-producing injurious agents, which may be microbic or chemic in nature. The "Migration Theory," the chief advocate of which is Deutschmann,<sup>1</sup>who thus states it: sympathetic
COURSE AND MANAGEMENT OF MYASTHENIA GRAVIS
Authors: David Grob
Journal: JAMA (1953)

Since myasthenia gravis is a disease that is subject to spontaneous remissions and exacerbations, it is difficult to evaluate the effect of procedures that are intended to alter the course of this disease. There has been considerable difference of opinion concerning the effect of thymectomy<sup>1</sup>and of irradiation of the thymus.<sup>2</sup>Preliminary observations on the effect of thymectomy suggested that the rate and degree of remission following this operation were greater than would be expected to occur spontaneously.<sup>3</sup>Because 12 years have elapsed since these observations were begun, a review of this problem, in which the course of patients who have had thymectomy or irradiation of the thymus are compared with patients of comparable severity of illness who have had neither procedure, seems appropriate. A total of 202 patients with generalized myasthenia gravis have been studied in the Johns Hopkins Hospital from 1 to 34 years, the
Impacted Lower Third Molar Fused with a Supernumerary Tooth —Diagnosis and Treatment Planning Using Cone‐Beam Computed Tomography
Authors: Osny Ferreira‐Junior, Luciana Dorigatti de Ávila, Marcelo Bonifácio da Silva Sampieri, Eduardo Dias‐Ribeiro, Wei‐liang Chen, Song Fan
Journal: International Journal of Oral Science (2009)

This paper reported a case of fusion between an impacted third molar and a supernumerary tooth, in which a surgical intervention was carried out, with the objective of removing the dental elements. The panoramic radiography was complemented by the Donovan's radiographic technique; but because of the proximity of the dental element to the mandibular ramus, it was not possible to have a final fusion diagnosis. Hence, the Cone‐Beam Computed Tomography—which provides precise three‐dimensional information—was used to determinate the fusion diagnosis and also to help in the surgical planning. In this case report we observed that the periapical, occlusal and panoramic were not able to show details which could only be examined through the cone‐beam computed tomography.
Hypersusceptibility to Vesicular Stomatitis Virus Infection in Dicer1-Deficient Mice Is Due to Impaired miR24 and miR93 Expression
Authors: Motoyuki Otsuka, Qing Jing, Philippe Georgel, Liguo New, Jianming Chen, Johann Mols, Young Jun Kang, Zhengfan Jiang, Xin Du, Ryan Cook, Subash C. Das, Asit K. Pattnaik, Bruce Beutler, Jiahuai Han
Journal: Immunity (2007)
Appearance of Ga-67 in the Stomach from Duodenogastric Reflux
Authors: DAVID L. CHAMOVITZ, BOLESLAW KNOBEL
Journal: Clinical Nuclear Medicine (1991)

A 35-year-old man was admitted because of protracted fever and vomiting. Past history was negative except for G6PD hemolytic anemia with cholecystectomy. Physical exam was normal. Normocytic and normochromic anemia with a hemoglobin of 10 g/dl and leukocytosis of 14,600mm3 were present. The patient improved without treatment and was discharged with presumed diagnosis of viral infection 7 weeks after onset of symptoms. Ga-67 scan initially suggested gastric lymphoma, but repeated Ga-67 and hepatobiliary scans proved duodenogastric reflux.
Acute failure of artificial heart valves.
Authors: P. M. Sagar, G. W. Dyke
Journal: BMJ (1988)

to isometric exercise in patients with neurocirculatory asthenia, a syndrome of easy fatigability without signs of organic disease.'Our patients with asthenia and healthy controls were all young men.The isometric work was done by squeezing a rubber ball at a force 20% of the maximal squeezing force for one minute.During this handgrip test the average increase in heart rate was similar in the two groups, and the diastolic blood pressure increased slightly (p<005) more in the asthenic group (18 mm Hg) than in the control group (12 mm Hg).Especially interesting was the fact that the increase in blood pressure was asso- ciated with an increase in the total peripheral vascular resistance in the asthenic patients but was due to an increase in cardiac output in the controls.Our conclusion was that in patients with neuro- circulatory asthenia central regulation of haemo- dynamics during isometric exercise is different from that in healthy controls.Thus we agree with Dr Stokes and coworkers that the easy fatigability in these patients is of central origin.The possible aberration in the circulatory regulation during isometric exercise which we observed in our asthmatic patients emphasises the fact that poor motivation is not the only form of "central impairment" that can explain the easy fatigability in effort syndromes.
READING AND WRITING FOR THE RECUMBENT
Authors: John Alexander
Journal: JAMA (1926)

Fatigue and eyestrain that result from writing by hand on a board held against the chest, or from reading from a book held in the hand, are not only harmful in themselves but may seriously impair the morale of patients with chronic disease who must lie flat in bed for a long time. Provision of facilities for reading and writing with ease may well dispel much of the dread with which most patients face prolonged confinement in bed, and may furnish many possibilities for occupational therapy and contentment. On extensive inquiry I find that the devices described in this article are unknown to the medical profession at large and therefore justify this brief notice. Typewriting may be as easily performed in the recumbent position as when sitting. A bedside table that is adjustable as to height and tilt (such as may be had at hospital supply stores) is put across
The issue is tissue
Authors: K. Subramaniam, H. C. Ee, S. Fermoyle, C. W. Siah
Journal: Gut (2010)

A 69-year-old man, otherwise well, except for ischaemic heart disease and asthma, presented with a 2 year history of crampy abdominal pain relieved with vomiting, intermittent diarrhoea up to 15 times per day and associated 20 kg weight loss. Physical examination revealed a soft abdomen with mild distension. Initial laboratory data were normal. Multiple stool cultures were negative. Plain abdominal radiography and CT revealed dilatation of multiple loops of small and large bowel.

Metabolic, autoimmune, infectious including HIV and tuberculosis), as well as a carcinoid screen including an octreotide scan …
Survival of patients ventilated in an intensive therapy unit.
Authors: J F Nunn, J S Milledge, J Singaraya
Journal: BMJ (1979)

The survival of patients who were artificially ventilated in an intensive therapy unit (ITU) of a district general hospital was studied. The first 100 such patients admitted were followed up for at least four years. Of these, 67 survived treatment in the ITU, 47 were discharged from hospital, and 30 survived four years. (Survival in the ITU of patients who did not require ventilation was 89%.) The effects of age, duration of ventilation, and disease were studied, and a higher survival was found in children, in patients ventilated for under 24 hours, and in patients admitted with drug overdosage. Survival was poor in patients aged over 75 and in those who required ventilation after cardiac arrest or myocardial infarction or for chronic obstructive lung disease. The cost of a bed in an ITUs to be used to the greatest effect it is important to define those patients who are most likely to benefit from the facilities they offer.
Effect of bacterial products on human ciliary function in vitro.
Authors: R Wilson, D Roberts, P Cole
Journal: Thorax (1985)

Ciliary activity protects the respiratory tract against inhaled particles, including bacteria, by transporting them trapped in mucus towards the pharynx. We have studied the effect of bacteria (Haemophilus influenzae, Staphylococcus aureus, and Pseudomonas aeruginosa) on human nasal cilia, measuring their in vitro ciliary beat frequency by a photometric technique. Supernatant fluids were obtained from 18 hour broth cultures by centrifugation alone, by filtration, and by lysis. Supernatants obtained from Ps aeruginosa and H influenzae caused a significantly lower ciliary beat frequency than controls (broth alone). Slowed cilia were dyskinetic and at times of maximal slowing ciliostasis occurred in some areas of the epithelium. A dose related effect was demonstrated. Abrogation of cilioinhibitory properties was achieved by heating the lysate to 56 degrees C for 30 minutes and by allowing the filtrate to stand at 37 degrees C for 120 minutes. Staphylococcal products were not cilioinhibitory. It is concluded that Ps aeruginosa and H influenzae release a factor (or factors) which causes slowing of human nasal cilia in vitro. The role of this factor in the pathogenesis of infection is discussed.
Obama seeks $213m to fund "precision medicine"
Authors: M. McCarthy
Journal: BMJ (2015)

In his 2016 budget submitted to Congress today President Barack Obama has asked for $213m (£140m; €190m) to fund a “precision medicine” initiative. The initiative would include a $130m program to create a “national research cohort” of a million or more volunteers whose genetic, medical, and lifestyle data would be collected for biomedical research.

Speaking at a White House event to announce the initiative on 30 January, Obama said that the goal of the precision medicine initiative will be to understand the differences between people, such as differences in their genetic makeup, to enable individualized treatments that would be most likely to be effective for each person. The approach, Obama said, promised to make it possible to deliver “the right treatments, at …
An In Vivo Cardiac Assay to Determine the Functional Consequences of Putative Long QT Syndrome Mutations
Authors: Chuanchau J. Jou, Spencer M. Barnett, Jian-Tao Bian, H. Cindy Weng, Xiaoming Sheng, Martin Tristani-Firouzi
Journal: Circulation Research (2013)

Rationale: Genetic testing for Long QT Syndrome is now a standard and integral component of clinical cardiology. A major obstacle to the interpretation of genetic findings is the lack of robust functional assays to determine the pathogenicity of identified gene variants in a high-throughput manner. Objective: The goal of this study was to design and test a high-throughput in vivo cardiac assay to distinguish between disease-causing and benign KCNH2 ( hERG1) variants, using the zebrafish as a model organism. Methods and Results: We tested the ability of previously characterized Long QT Syndrome hERG1 mutations and polymorphisms to restore normal repolarization in the kcnh2 -knockdown embryonic zebrafish. The cardiac assay correctly identified a benign variant in 9 of 10 cases (negative predictive value 90%), whereas correctly identifying a disease-causing variant in 39/39 cases (positive predictive value 100%). Conclusions: The in vivo zebrafish cardiac assay approaches the accuracy of the current benchmark in vitro assay for the detection of disease-causing mutations, and is far superior in terms of throughput rate. Together with emerging algorithms for interpreting a positive long QT syndrome genetic test, the zebrafish cardiac assay provides an additional tool for the final determination of pathogenicity of gene variants identified in long QT syndrome genetic screening.
Retraction: Barlogie et al. Duration of Survival in Patients with Myeloma Treated with Thalidomide. N Engl J Med 2008;359:210-2.
Authors: Bart Barlogie, John D. Shaughnessy, John Crowley
Journal: New England Journal of Medicine (2008)

To the Editor: We wish to retract our letter to the editor, “Duration of Survival in Patients with Myeloma Treated with Thalidomide,” which was published in the Journal on July 10, 2008.1 The content of this letter, submitted in February 2008 and accepted by the Journal in March 2008, largely duplicates the data that were published online by Blood on May 20, 2008.2
Programmed "Trendscription"
Authors: Bernard Lown
Journal: JAMA (1975)

A new approach to monitoring of episodic but frequently recurring arrhythmias has been developed, consisting of condensation of electrocardiographic information on a special drum recorder, a programmer that permits selection of intervals and durations for monitoring, and a telemetry unit for transmission of the electrocardiographic signal. We used this system to manage three selected cases. (<i>JAMA</i>232:39-43, 1975)