tbuckley/cabot-search huggingface dataset:
Influence of clinical factors, diet, and drugs on the human upper gastrointestinal glutathione system
Authors: H Hoensch
Journal: Gut (2002)

Background: Glutathione (GSH) and the cytosolic glutathione S-transferases (GSTs) protect the gastrointestinal mucosa against the toxic effects of a wide variety of compounds, such as reactive oxygen species and electrophiles. Aims: We wished to investigate the distribution along the upper gastrointestinal mucosa and the influence of clinical variables on components of the GSH system to learn more about factors which control its cytoprotective properties. Methods: Antral and duodenal biopsies of normal appearing mucosa were collected from 202 patients (104 males, 98 females; mean age 62 years) undergoing upper gastrointestinal endoscopy. GSH content was examined by high pressure liquid chromatography, GST enzyme activity by 1-chloro-, 2, 4-dinitrobenzene conjugation, and levels of the GST classes alpha, pi, and theta by western blot. Results: GSH, GST enzyme activity, and GST alpha levels were significantly lower (p&lt;0.001) in the antrum than in the duodenum (antrum <i>v</i> duodenum: GSH 23.0 (0.7) <i>v</i> 35.0 (1.0) nmol/mg protein; GST activity 626 (19) <i>v</i> 832 (22) nmol/mg protein/min; GST alpha 4.5 (0.5) <i>v</i> 20.0 (0.7) μg/mg protein) while GST pi content was significantly higher (p&lt;0.001) in antral than in duodenal biopsies (16.5 (0.7) <i>v</i> 11.2 (0.5) μg/mg protein). Antral GSH and GST activities were markedly lower in males compared with females (p&lt;0.01). Some drugs (cisapride, diuretics, cortisol, analgesics) increased GST pi and GST alpha content but cytostatic drugs suppressed duodenal GST activity. High intake (&gt;3 days a week) of vegetables enhanced duodenal GST alpha and GST pi and high intake of fruits the antral content of GST theta1. Conclusions: The gastrointestinal GSH system represents the antitoxic barrier of the mucosa; its activity is influenced by localisation, sex, and drugs, and its enzymes are stimulated by a high intake of vegetables and fruits.
Thoughts on future doctors
Authors: Richard Smith
Journal: Journal of the Royal Society of Medicine (2009)

Every few years, responding perhaps to some deep anxiety, medical organizations think about ‘the role of the doctor’ or ‘the future doctor’. We are in such a phase at the moment – prompted particularly by the disaster of the medical training application service and the subsequent inquiry.1 The ‘leaders of UK medicine’ (whoever they are) have produced a statement on the role of the doctor,2 and the Royal College of Physicians is following up its report on medical professionalism with another on the future doctor.3

For some unknown reason (perhaps random selection), the College of Physicians working party on the future doctor asks me to give evidence. ‘But you're not a practising doctor. What do you know?’ says a doctor friend. Good point, but as the cliche has it, ‘doctoring is too important to be left to doctors’. And besides I'm sort of a doctor, and I know thousands of doctors. I live in a strange but enticing hinterland of doctor, patient, manager, busybody, amateur futurologist and loud mouth. So I'm going.

The first thing that strikes me about the working party is its youth. There are three old guys, but everybody else is young – and mostly women. If the future of the College of Physicians belongs to young women, then it's bright.
Cockroach allergens and asthma in Brazil: Identification of tropomyosin as a major allergen with potential cross-reactivity with mite and shrimp allergens☆☆☆★
Authors: Ana Beatriz R. Santos, Martin D. Chapman, Rob C. Aalberse, Lisa D. Vailes, Virginia P.L. Ferriani, Constance Oliver, M.Candida Rizzo, Charles K. Naspitz, L.Karla Arruda
Journal: Journal of Allergy and Clinical Immunology (1999)
The role of Ephs, Ephrins, and growth factors in Kaposi sarcoma and implications of EphrinB2 blockade
Authors: Jeffrey S. Scehnet, Eric J. Ley, Valery Krasnoperov, Ren Liu, Parmeet K. Manchanda, Eric Sjoberg, Anna P. Kostecke, Sachin Gupta, S. Ram Kumar, Parkash S. Gill
Journal: Blood (2008)
Eradication of Helicobacter pylori Infection in Primary Low-Grade Gastric Lymphoma of Mucosa-Associated Lymphoid Tissue
Authors: Enrico Roggero
Journal: Annals of Internal Medicine (1995)

Objective: To determine the effect of eradicating Helicobacter pylori infection on the course of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Design: Prospective cohort study. Setting: University internal medicine clinics, a referral oncology center in southern Switzerland, and a gastroenterology referral center in northern Italy. Patients: 26 patients with localized primary low-grade gastric MALT lymphoma. Intervention: Treatment for H. pylori infection (bismuth or omeprazole or both, amoxicillin, and metronidazole for 14 days). Main Outcome Measures: Endoscopic biopsy specimens of the gastric mucosa were obtained every 3 to 6 months after treatment for H. pylori infection. Results: Helicobacter pylori was completely eradicated in 25 of 26 patients, but 4 patients needed second-line antibiotic treatment to eradicate the microorganism. Disappearance or almost total regression of the lymphomatous tissue was observed in 15 of the 25 evaluable patients (60%; CI, 39% to 79%); however, disappearance or almost total regression was evident in the first biopsy specimen after treatment for H. pylori infection in only 8 of the 15 patients. Conclusions: Our study confirms recent anecdotal reports of regression of gastric MALT lymphoma after eradication of H. pylori and indicates that the growth of these extranodal lymphomas may depend on H. pylori.
A novel VIM‐type metallo‐beta‐lactamase (VIM‐14) in a Pseudomonas aeruginosa clinical isolate from a neonatal intensive care unit
Authors: A. Mazzariol, C. Mammina, R. Koncan, V. Di Gaetano, P. Di Carlo, D. Cipolla, G. Corsello, G. Cornaglia
Journal: Clinical Microbiology and Infection (2010)
Brighton considers opening UK's first safe drug consumption rooms
Authors: J. Wise
Journal: BMJ (2013)

Brighton and Hove City Council is considering whether to provide rooms where drug users could use illegal drugs safely, as a way to reduce drug related deaths.

The recommendation comes from the Independent Drugs Commission for Brighton and Hove after a year long investigation into how services in the city could best reduce the harm caused by drugs.1

In 2000 Brighton was branded the “drugs death capital of the UK” when 67 people died from drug misuse. This figure has since been reduced to 20 deaths a year, but the commission said that the city still had more than 2000 problem heroin and cocaine users.

The commission conducted a series of discussions and consultations with …
Enhanced bacterial phagocytosis by peripheral blood monocytes in rheumatoid arthritis.
Authors: M M Steven, S E Lennie, R D Sturrock, C G Gemmell
Journal: Annals of the Rheumatic Diseases (1984)

To assess the functional state of peripheral blood monocytes in rheumatoid arthritis, we have measured phagocytosis of Staphylococcus aureus and Proteus mirabilis in 48 patients and 28 controls. Using radiolabelled bacteria preopsonised in normal human serum we have demonstrated significantly enhanced uptake of both organisms by patients9 monocytes: (Median % uptake Staph. aureus: patients = 35.8; controls = 19.3; p less than 0.001. Median % uptake P. mirabilis: patients = 32.3; controls = 19.8; p less than 0.01.) These results indicate that patients9 monocytes exist in an activated state, which may be important in the pathogenesis of rheumatoid arthritis.
CD4+ and CD8+ T cell–dependent antiviral immunity requires STIM1 and STIM2
Authors: Patrick J. Shaw, Carl Weidinger, Martin Vaeth, Kevin Luethy, Susan M. Kaech, Stefan Feske
Journal: Journal of Clinical Investigation (2014)

Calcium signaling is critical for lymphocyte function, and intracellular Ca2+ concentrations are regulated by store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ (CRAC) channels. In patients, loss-of-function mutations in CRAC channel components ORAI1 and STIM1 abolish SOCE and are associated with recurrent and chronic viral infections. Here, using mice with conditional deletion of Stim1 and its homolog Stim2 in T cells, we determined that both components are required for the maintenance of virus-specific memory CD8+ T cells and recall responses following secondary infection. In the absence of STIM1 and STIM2, acute viral infections became chronic. Early during infection, STIM1 and STIM2 were required for the differentiation of naive CD8+ T cells into fully functional cytolytic effector cells and mediated the production of cytokines and prevented cellular exhaustion in viral-specific CD8+ effector T cells. Importantly, memory and recall responses by CD8+ T cells required expression of STIM1 and STIM2 in CD4+ T cells. CD4+ T cells lacking STIM1 and STIM2 were unable to provide "help" to CD8+ T cells due to aberrant regulation of CD40L expression. Together, our data indicate that STIM1, STIM2, and CRAC channel function play distinct but synergistic roles in CD4+ and CD8+ T cells during antiviral immunity.
Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID)
Authors: Mariell Jessup, Barry Greenberg, Donna Mancini, Thomas Cappola, Daniel F. Pauly, Brian Jaski, Alex Yaroshinsky, Krisztina M. Zsebo, Howard Dittrich, Roger J. Hajjar
Journal: Circulation (2011)

Adeno-associated virus type 1/sarcoplasmic reticulum Ca(2+)-ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure.Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca(2+)-ATPase or placebo. Seven efficacy parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving efficacy at 6 months in the group-level (concordant improvement in 7 efficacy parameters and no clinically significant worsening in any parameter), individual-level (total score for predefined clinically meaningful changes in 7 efficacy parameters), or outcome end points (cardiovascular hospitalizations and time to terminal events). Efficacy in 1 analysis had to be associated with at least a positive trend in the other 2 analyses. This combination of requirements resulted in a probability of success by chance alone of 2.7%. The high-dose group versus placebo met the prespecified criteria for success at the group-level, individual-level, and outcome analyses (cardiovascular hospitalizations) at 6 months (confirmed at 12 months) and demonstrated improvement or stabilization in New York Heart Association class, Minnesota Living With Heart Failure Questionnaire, 6-minute walk test, peak maximum oxygen consumption, N-terminal prohormone brain natriuretic peptide levels, and left ventricular end-systolic volume. Significant increases in time to clinical events and decreased frequency of cardiovascular events were observed at 12 months (hazard ratio=0.12; P=0.003), and mean duration of cardiovascular hospitalizations over 12 months was substantially decreased (0.4 versus 4.5 days; P=0.05) on high-dose treatment versus placebo. There were no untoward safety findings.The Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) study demonstrated safety and suggested benefit of adeno-associated virus type 1/sarcoplasmic reticulum Ca(2+)-ATPase in advanced heart failure, supporting larger confirmatory trials.http://www.clinicaltrials.gov. Unique identifier: NCT00454818.
North–South Colonization Associated with Local Adaptation of the Wild Tomato Species<i>Solanum chilense</i>
Authors: Katharina B. Böndel, Hilde Lainer, Tetyana Nosenko, Mamadou Mboup, Aurélien Tellier, Wolfgang Stephan
Journal: Molecular Biology and Evolution (2015)

After colonization population sizes may vary across the species range depending on environmental conditions and following colonizations. An interesting question is whether local adaptation occurs more frequently in large ancestral populations or in small derived populations. A higher number of new mutations and a lower effect of genetic drift should favor selection in large populations, whereas small derived populations may require an initial local adaptation event to facilitate the colonization of new habitats. Wild tomatoes are native to a broad range of different habitats characterized by variable abiotic conditions in South America, and represent an ideal system to study this interplay between demography and natural selection. Population genetic analyses and statistical inference of past demography were conducted on pooled-sequencing data from 30 genes (8,080 single nucleotide polymorphisms) from an extensive sampling of 23 Solanum chilense populations over Chile and Peru. We reveal first a north–south colonization associated with relaxed purifying selection in the south as shown by a decrease of genetic variation and an increasing proportion of nonsynonymous polymorphism from north to south, and population substructure with at least four genetic groups. Second, we uncover a dual picture of adaptation consisting of 1) a decreasing proportion of adaptive amino acid substitutions from north to south suggesting that adaptation is favored in large populations, whereas 2) signatures of local adaptation predominantly occur in the smaller populations from the marginal ranges in the south.
Autologous neutrophil derived supernatants inhibit endothelium dependent relaxation in human coronary bypass graft
Authors: J. J Liu, J. R Chen, C. J Bradley, B. Xie, C. I Johnston, B. F Buxton
Journal: Cardiovascular Research (1994)

Spasm of internal mammary artery is a problem during coronary artery bypass grafting. The mechanism is unknown. The aim of this study was to determine whether supernatants derived from neutrophils affected endothelium dependent relaxation of human internal mammary artery.The studies involved use of an organ chamber, measurement of cytosolic Ca2+, electron microscopy, and chemical characterisation.Autologous neutrophils and internal mammary artery were obtained from patients undergoing the bypass grafting. Supernatants derived from the neutrophils were used to treat the patients' internal mammary artery rings. The results showed that the supernatants derived from 1 x 10(3)-5 x 10(6) cells.ml-1 neutrophils produced a potent concentration dependent inhibition of the endothelium dependent relaxation to ATP, acetylcholine, and the calcium ionophore A23187, but not the endothelium independent relaxation to sodium nitroprusside. In cultured human endothelial cells, the neutrophil derived supernatants induced an increase in cytosolic calcium ([Ca2+]i), caused calcium oscillations, and desensitised the ATP induced increase in [Ca2+]i. The increased [Ca2+]i resulted from a calcium influx. The supernatants also induced an increase in vesicle formation and possibly exocytosis in the internal mammary artery endothelium. Chemical characterisation showed that the effect of the supernatants was caused by a factor that is stable to heat, extreme pH and protease, is negatively charged and weakly hydrophobic, and has a molecular weight under 500 Dalton.Autologous neutrophils release a stable non-protein small molecule that disturbs internal mammary artery endothelial function. Since it raises [Ca2+]i and causes possible exocytosis, it may have functions beyond its inhibition of vascular relaxation. This factor could be one of the contributors to internal mammary artery spasm and late atherosclerosis.
Systematic review of peer support for breastfeeding continuation: metaregression analysis of the effect of setting, intensity, and timing
Authors: K. Jolly, L. Ingram, K. S. Khan, J. J. Deeks, N. Freemantle, C. MacArthur
Journal: BMJ (2012)

<b>Objective</b> To examine the effect of setting, intensity, and timing of peer support on breast feeding. <b>Design</b> Systematic review and metaregression analysis of randomised controlled trials. <b>Data sources</b> Cochrane Library, Medline, CINAHL, the National Research Register, and British Nursing Index were searched from inception or from 1980 to 2011. <b>Review methods</b> Study selection, data abstraction, and quality assessment were carried out independently and in duplicate. Risk ratios and 95% confidence intervals were calculated for individual studies and pooled. Effects were estimated for studies grouped according to setting (high income countries, low or middle income countries, and the United Kingdom), intensity (&lt;5 and ≥5 planned contacts), and timing of peer support (postnatal period with or without antenatal care), and analysed using metaregression for any and exclusive breast feeding at last study follow-up. <b>Results</b> Peer support interventions had a significantly greater effect on any breast feeding in low or middle income countries (P&lt;0.001), reducing the risk of not breast feeding at all by 30% (relative risk 0.70, 95% confidence interval 0.60 to 0.82) compared with a reduction of 7% (0.93, 0.87 to 1.00) in high income countries. Similarly, the risk of non-exclusive breast feeding decreased significantly more in low or middle income countries than in high income countries: 37% (0.63, 0.52 to 0.78) compared with 10% (0.90, 0.85 to 0.97); P=0.01. No significant effect on breast feeding was observed in UK based studies. Peer support had a greater effect on any breastfeeding rates when given at higher intensity (P=0.02) and only delivered in the postnatal period (P&lt;0.001), although no differences were observed of its effect on exclusive breastfeeding rates by intensity or timing. <b>Conclusion</b> Although peer support interventions increase breastfeeding continuation in low or middle income countries, especially exclusive breast feeding, this does not seem to apply in high income countries, particularly the United Kingdom, where breastfeeding support is part of routine postnatal healthcare. Peer support of low intensity does not seem to be effective. Policy relating to provision of peer support should be based on more specific evidence on setting and any new peer services in high income countries need to undergo concurrent evaluation.
Getting your "T" up
Authors: D. Kamerow
Journal: BMJ (2014)

Big pharma creates a new disease: low testosterone



I’ve been seeing a lot of TV commercials for testosterone replacement therapy (TRT) recently. It must be because the manufacturers like the demographics of the two main types of programs I watch: network news and sports. That’s where you find the middle aged and older guys, as well as their wives, who can actually get them to see their doctors. Pushing through the ads for overactive bladder, arthritis pain, and, yes, erectile dysfunction treatments are now numerous questions about whether I have “low T” or not.

It used to be that TRT was reserved for clear cases of hypogonadism, either primary (due to testicular failure) or secondary (such as from pituitary tumors). Because oral testosterone is largely ineffective, these patients would be treated with regular testosterone injections, at considerable cost and inconvenience, resulting in widely varying blood concentrations. Now we have several non-injectable ways to deliver stable testosterone levels: patch, gel, subdermal pellet, buccal tablet, and even an underarm roll-on.

Until recently, however, TRT was a relatively small market. In 2002 only about …
It's “wrong” to put patients' records on IT system without explicit consent, MPs are told
Authors: Adrian O'Dowd
Journal: BMJ (2007)

An influential group of MPs has claimed that widespread financial incompetence is adding to the cost of the United Kingdom's controversial private finance initiative (PFI).The House of Commons Committee of Public Accounts made its new attack on the PFI after it discovered that the government had clawed back £100m (€145m; $200m) less than was predicted from the new private-public profit sharing schemes.The committee's chairman, the Conservative MP Edward Leigh, blamed the loss on the failure of Treasury officials to oversee key refinancing arrangements.In 2002 ministers introduced changes so that public sector bodies could share in some of the financial gains when big PFI loans were rearranged.Typically, these loans were renegotiated on a more favourable basis once PFI projects had been completed and the risks involved were lower.However, left to their own devices, officials in local hospitals had been out of their depth negotiating with their counterparts in the private sector, the committee says.In 2003 the Office of Government Commerce, which then had responsibility for PFI policy, told the public accounts committee that it expected the public sector to receive between £175m and £200m from the voluntary sharing arrangements in early PFI deals.However, up to December 2006 the government had secured the right to gains of only £93m."Proceeds gained by the public sector from PFI debt refinancing under the voluntary code for the sharing of gains are currently well short of expectations" said Mr Leigh.
Category Learning in the Brain
Authors: Carol A. Seger, Earl K. Miller
Journal: Annual Review of Neuroscience (2010)

The ability to group items and events into functional categories is a fundamental characteristic of sophisticated thought. It is subserved by plasticity in many neural systems, including neocortical regions (sensory, prefrontal, parietal, and motor cortex), the medial temporal lobe, the basal ganglia, and midbrain dopaminergic systems. These systems interact during category learning. Corticostriatal loops may mediate recursive, bootstrapping interactions between fast reward-gated plasticity in the basal ganglia and slow reward-shaded plasticity in the cortex. This can provide a balance between acquisition of details of experiences and generalization across them. Interactions between the corticostriatal loops can integrate perceptual, response, and feedback-related aspects of the task and mediate the shift from novice to skilled performance. The basal ganglia and medial temporal lobe interact competitively or cooperatively, depending on the demands of the learning task.
Prevalence and incidence of respiratory symptoms in relation to indoor dampness: the RHINE study
Authors: M I Gunnbjornsdottir
Journal: Thorax (2006)

An association between indoor dampness and respiratory symptoms has been reported, but dampness as a risk factor for the onset or remission of respiratory symptoms and asthma is not well documented.This follow up study included 16 190 subjects from Iceland, Norway, Sweden, Denmark, and Estonia who had participated in the European Community Respiratory Health Survey (ECRHS I). Eight years later the same subjects answered a postal questionnaire that included questions on respiratory symptoms and indicators of indoor dampness.Subjects living in damp housing (18%) had a significantly (p<0.001) higher prevalence of wheeze (19.1% v 26.0%), nocturnal breathlessness (4.4% v 8.4%), nocturnal cough (27.2% v 36.5%), productive cough (16.6% v 22.3%) and asthma (6.0% v 7.7%). These associations remained significant after adjusting for possible confounders. Indoor dampness was a risk factor for onset of respiratory symptoms but not for asthma onset in the longitudinal analysis (OR 1.13, 95% CI 0.92 to 1.40). Remission of nocturnal symptoms was less common in damp homes (OR 0.84, 95% CI 0.73 to 0.97).Subjects living in damp housing had a higher prevalence of respiratory symptoms and asthma. Onset of respiratory symptoms was more common and remission of nocturnal respiratory symptoms was less common in subjects living in damp housing.