tbuckley/cabot-search huggingface dataset:
Role of Interferon- γ and Nitric Oxide in Pulmonary Edema and Death Induced by Lipopolysaccharide
Authors: HUBERTINE HEREMANS, CHRISTIANE DILLEN, MARLEEN GROENEN, PATRICK MATTHYS, ALFONS BILLIAU
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Mice given lipopolysaccharide (LPS) intravenously developed lung edema, which was maximum after 6 h. Tumor necrosis factor, interleukin 12 (IL-12), IL-6, and interferon- γ (IFN- γ ) appeared in the serum, and levels of nitrogen oxide (NO) derivatives were increased in serum and bronchoalveolar fluid. Mice pretreated with neutralizing anti-IFN- γ antibodies had lower serum levels of IFN- γ , and fewer died. However, levels of other cytokines and NO derivatives as well as lung edema were unchanged. If IFN- γ and LPS were given together, pulmonary edema was less, but levels of cytokines and NO derivatives in serum were raised, and the mortality was greater. IFN- γ receptor knockout mice had more edema after LPS, but were less sensitive to the lethal effects. Treatment with anti-IL-12 antibody inhibited IFN- γ induction and reduced mortality, but had no effect on the lung edema; exogenous IL-12 also failed to affect edema, but boosted serum cytokine levels and increased the mortality. Aminoguanidine, an inhibitor of NO synthase, protected against pulmonary edema, but did not modify the lethal effects of LPS. Clearly, in this model, early pulmonary edema and lethality are not directly related, and induced IFN- γ has no role in causing early lung edema, but augments other events that result in death. Heremans H, Dillen C, Groenen M, Matthys P, Billiau A. Role of interferon- γ and nitric oxide in pulmonary edema and death induced by lipopolysaccharide.
Economic Savings Versus Health Losses: The Cost-Effectiveness of Generic Antiretroviral Therapy in the United States
Authors: Rochelle P. Walensky, Paul E. Sax, Yoriko M. Nakamura, Milton C. Weinstein, Pamela P. Pei, Kenneth A. Freedberg, A. David Paltiel, Bruce R. Schackman
Journal: Annals of Internal Medicine (2013)

Chinese translation Background: U.S. HIV treatment guidelines recommend branded once-daily, 1-pill efavirenz–emtricitabine–tenofovir as first-line antiretroviral therapy (ART). With the anticipated approval of generic efavirenz in the United States, a once-daily, 3-pill alternative (generic efavirenz, generic lamivudine, and tenofovir) will decrease cost but may reduce adherence and virologic suppression. Objective: To assess the clinical effect, costs, and cost-effectiveness of a 3-pill, generic-based regimen compared with a branded, coformulated regimen and to project the potential national savings in the first year of a switch to generic-based ART. Design: Mathematical simulation of HIV disease. Setting: United States. Patients: HIV-infected persons. Intervention: No ART (for comparison); 3-pill, generic-based ART; and branded ART. Measurements: Quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICERs) in dollars per quality-adjusted life-year (QALY). Results: Compared with no ART, generic-based ART has an ICER of $21 100/QALY. Compared with generic-based ART, branded ART increases lifetime costs by $42 500 and per-person survival gains by 0.37 QALYs for an ICER of $114 800/QALY. Estimated first-year savings, if all eligible U.S. patients start or switch to generic-based ART, are $920 million. Most plausible assumptions about generic-based ART efficacy and costs lead to branded ART ICERs greater than $100 000/QALY. Limitation: The efficacy and price reduction associated with generic drugs are unknown, and estimates are intended to be conservative. Conclusion: Compared with a slightly less effective generic-based regimen, the cost-effectiveness of first-line branded ART exceeds $100 000/QALY. Generic-based ART in the United States could yield substantial budgetary savings to HIV programs. Primary Funding Source: National Institute of Allergy and Infectious Diseases.
Reaccumulation of thyroglobulin and colloid in rat and mouse thyroid follicles during intense thyrotropin stimulation. A clue to the pathogenesis of colloid goiters.
Authors: H Gerber, H Studer, A Conti, H Engler, H Kohler, A Haeberli
Journal: Journal of Clinical Investigation (1981)

Since Marine's observations some 50 years ago, it has been generally accepted that colloid goiters invariably result from colloid repletion of originally hyperplastic goiters after cessation of the goitrogenic stimulus. However, clinical observations suggest that many goiters never go through a stage of hyperplasia, but are colloid-rich from the beginning. We have injected rats and mice with thyrotropin (TSH), three times a day for 4 d, while the animals were kept on an iodine-rich diet (HID). Additional groups of animals were fed an iodine-poor diet (LID) or a diet containing 0.15% propylthiouracil (PTU) or 1% sodium perchlorate (ClO4). At intervals, thyroid weight, DNA, iodine and thyroglobulin content, thyroglobulin iodination, and intracellular droplet formation were measured. Histologic sections were also prepared and stained with periodic acid Schiff. Furthermore, thyroxine concentration was measured in the serum. Thyroglobulin content dropped by approximately 30% in HID animals but by 60% in all other groups 1 d after starting TSH. Thereafter, thyroglobulin reaccumulation occurred and droplet formation correspondingly decreased despite continuous heavy TSH stimulation. The largest amount of thyroglobulin was reaccumulated in HID animals followed by the PTU/LID groups, whereas no reaccumulation was observed in the ClO4 group. Reaccumulation of thyroglobulin only occurred if there was concomitant organification of at least some iodine. The subsequent phases of depletion and reaccumulation of thyroglobulin were mirrored by the morphology of the follicular lumina, the staining properties of the colloid and the serum T4 concentration. These observations suggest that endocytosis gradually becomes refractory to continuous TSH stimulation if a certain minimal amount of iodine is available for organic binding. Thus, primarily colloid-rich goiters may form in the presence of continuously higher than normal thyrotropin levels without a previous stage of follicular hyperplasia. The view should be revised that accumulation of colloid and intense thyrotropin stimulation are mutually exclusive events.
Peutz-Jeghers syndrome associated with primary malignant melanoma of the rectum
Authors: S.S. WONG, S. RAJAKULENDRAN
Journal: British Journal of Dermatology (1996)

An 85‐year‐old Chinese woman was found to have mucocutaneous pigmentation involving the lips, buccal mucosa, hard palate and the buttocks when she presented with primary malignant melanoma of the rectum. Multiple brown‐black pigmentation was also noted in the anal canal and the adjacent mucosa surrounding the tumour. This is the first report of Peutz‐Jeghers syndrome associated with malignant melanoma of the rectum.
Pet-1 ETS Gene Plays a Critical Role in 5-HT Neuron Development and Is Required for Normal Anxiety-like and Aggressive Behavior
Authors: Timothy J. Hendricks, Dmitry V. Fyodorov, Lauren J. Wegman, Nadia B. Lelutiu, Elizabeth A. Pehek, Bryan Yamamoto, Jerry Silver, Edwin J. Weeber, J.David Sweatt, Evan S. Deneris
Journal: Neuron (2003)
Diacylglycerol metabolism in mast cells: a potential role in membrane fusion and arachidonic acid release.
Authors: D A Kennerly, T J Sullivan, P Sylwester, C W Parker
Journal: The Journal of Experimental Medicine (1979)

Purified rat peritoneal mast cells stimulated with the polycationic histamine-releasing agent compound 48/80 demonstrated a two- to four-fold increase in cellular levels of 1,2-diacylglycerol (DAG) within 1 min as detected by radioactive labeling and direct quantitation experiments. When 2-[1-14C]arachidonoyl-DAG was incubated in the presence of mast-cell homogenates, a rapid conversion to free arachidonate, and to a lesser extent, to monoacylglycerol, triglyceride, and phospholipid was observed. The release of arachidonate was proportional to the amount of broken-cell preparation added and the time of incubation, was prevented by preheating mast-cell preparations, and did not occur when 1-[1-14C]arachidonoyl-phosphatidylcholine was used as substrate, suggesting that the degradation was mediated by an enzyme with Dag-lipase activity. Although much work remains to be done to clarify the precise role of DAG in mast cells, DAG metabolism may be involved in secretion by generating substances which may faciliate membrane fusion and also in arachidonic acid-derived mediator formation by liberating esterified arachidonic acid from mast-cell lipids. Taken together, these studies indicate that the formation of DAG may play a central role in mast-cell function.
Non-traumatic rhabdomyolysis: the emerging role of CYP 3A4 in diabetes mellitus
Authors: George I Varughese, John H B Scarpello
Journal: Journal of the Royal Society of Medicine (2006)

The editorial 'Too little quality; too many doctors' (June 2006 JRSM 1 ) is incorrect to suggest that the General Medical Council (GMC) had a 'sudden demand for overseas graduates to have a work permit'.The GMC does not have any visa requirements for international medical graduates (IMGs).The Home Office is responsible for setting visa requirements.International medical graduates are responsible for ensuring that they have the appropriate visa when they enter the UK.
Primary Adult Soft Tissue Sarcoma: Time-Dependent Influence of Prognostic Variables
Authors: Alexander Stojadinovic, Denis H.Y. Leung, Peter Allen, Jonathan J. Lewis, David P. Jaques, Murray F. Brennan
Journal: Journal of Clinical Oncology (2002)

To define prognostic factors for postrelapse survival and their time-dependent influence for adult soft tissue sarcoma (STS).We analyzed 2,123 patients with completely resected localized primary STS treated from 1982 to 1999. Variables studied included tumor site, size, depth, grade, and resection margin but not treatment other than resection. Landmark time frames were used to assess the influence of disease-free interval (DFI) on disease-specific survival (DSS). DSS was estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed using log-rank test and the Cox proportional hazards regression model. Time-dependent stepwise regression analysis evaluated the time-dependent influence of each variable.Two thirds of recurrences developed within 2 years of initial resection. Tumor size (P <.001), grade (P <.001), and microscopic resection margin (P <.001) independently predicted DSS for all STS. Size and grade independently predicted early (DFI <or= 3 years) and margin late (DFI > 3 years) DSS. Risk of tumor-related death was the same across all sites 3 years postresection and decreased significantly for extremity/trunk STS when DFI exceeded 3 years (P <.001). Influence of initial high-risk factors for tumor-related mortality in extremity/trunk STS decreased by 40% 3 years postresection, but their influence over DSS for non-extremity/trunk sites remained constant over time. Likelihood of complete resection after recurrence (all sites) increased with DFI (9% and 33% for DFI < 6 and > 36 months, respectively).Tumor size, grade, and resection margin predict outcome for completely resected STS, and their influence for DSS is time- and site-dependent. The influence of prognostic factors changes over the natural history of extremity/trunk STS. Time to recurrence exerts significant influence over complete resection rates for recurrent disease.
Ethnicity, Race, and Baseline Retinopathy Correlates in the Veterans Affairs Diabetes Trial
Authors: Nicholas Emanuele, Jerome Sacks, Ronald Klein, Domenic Reda, Robert Anderson, William Duckworth, Carlos Abraira
Journal: Diabetes Care (2005)

The Veterans Affairs Diabetes Trial (VADT) cohort is enriched with approximately 20% Hispanics and 20% African Americans, affording a unique opportunity to study ethnic differences in retinopathy.Cross-sectional analyses on the baseline seven-field stereo fundus photos of 1,283 patients are reported here. Diabetic retinopathy scores are grouped into four classes of increasing severity: none (10-14), minimal nonproliferative diabetic retinopathy (NPDR) (15-39), moderate to severe NPDR (40-59), and proliferative diabetic retinopathy (60+). These four groups have also been dichotomized to none or minimal (10-39) and moderate to severe diabetic retinopathy (40+).The prevalence of diabetic retinopathy scores >40 was higher for Hispanics (36%) and African Americans (29%) than for non-Hispanic whites (22%). The difference between Hispanics and non-Hispanic whites was significant (P < 0.05). Similarly, the prevalence of diabetic retinopathy scores >40 was significantly higher in African Americans than in non-Hispanic whites (P < 0.05). These differences could not be accounted for by an imbalance in traditional risk factors such as age, duration of diagnosed diabetes, HbA(1c) (A1C), and blood pressure. Diabetic retinopathy severity scores were also significantly associated with increasing years of disease duration, A1C, systolic and diastolic blood pressure, the degree of microalbuminuria, fibrinogen, and the percentage of patients with amputations. There was no relationship between retinopathy severity and the percentage of people who had strokes or cardiac revascularization procedures. There was an inverse relationship between retinopathy severity and total cholesterol, triglycerides, and plasminogen activator inhibitor-1 as well as with smoking history. Diabetic retinopathy scores were not associated with age.In addition to many well-known associations with retinopathy, a higher frequency of severe diabetic retinopathy was found in the Hispanic and African-American patients at entry into the VADT that is not accounted for by traditional risk factors for diabetic retinopathy, and these substantial ethnic differences remain to be explained.
EFFECTS OF CHRONIC HYPERCAPNIA ON ELECTROLYTE AND ACID-BASE EQUILIBRIUM. III. CHARACTERISTICS OF THE ADAPTIVE AND RECOVERY PROCESS AS EVALUATED BY PROVISION OF ALKALI*
Authors: Charles van Ypersele de Strihou, Paul F. Gulyassy, William B. Schwartz
Journal: Journal of Clinical Investigation (1962)

to assess the renal reabsorptive capacity after restoration of normal carbon dioxide tension in animals maintained on a high-bicarbonate
Remarks on THE TREATMENT OF GANGRENE
Authors: W. S. Handley
Journal: BMJ (1928)

FRoM the fact that Professor Leriehe was originially asked to open this discussion, and tlhat, failinig hiim, I liave been aslked to do so, I gather that the initerest of the occasion is expected to cenitre on lthe more recenit methocds of vaso- motor surgery in relationi to gangrenle.I may be absolved, tlherefore, in opening the discussion, from attempting a general sur-vey of the wlhole subject, anid my remarks-must not be takert as limiting the scope of tlle subsequent discussion .A word of gratitude to the plhysicians is ap)propriate, and especially to Dr. Banting, for the gift of insulin, which has enitirely clhanged the outlook in cases of amputa- tioni for diabetic gangrene anid in other operations upon diabetics.In such cases the co-operatioln of a physician is now essenitial, anid when the urine lhas been rendered sugar- free by inssulin tlle surgeon can intervene almost as confidently as in the non-diabetic; such at any rate is my experience.
Limitation of myocardial infarct size by superoxide dismutase as an adjunct to reperfusion after different durations of coronary occlusion in the pig.
Authors: U Näslund, S Häggmark, G Johansson, S L Marklund, S Reiz
Journal: Circulation Research (1990)

Superoxide dismutase (SOD) has been documented to limit myocardial infarct size in the richly collateralized dog heart. This study was designed to explore this concept in a low-collateralized animal model. A blind, randomized, placebo-controlled protocol was used in 65 pentobarbital-anesthetized pigs subjected to closed-chest left anterior descending coronary artery occlusion for 30 (n = 22), 60 (n = 22), and 90 (n = 14) minutes followed by reperfusion up to 24 hours from the start of occlusion. Another seven control pigs were subjected to 24 hours of permanent occlusion. A total dose of 9 mg/kg bovine CuZn SOD was administered as a bolus injection immediately before reperfusion followed by a 1-hour infusion. Infarct size was assessed by tetrazolium staining. Myocardium at risk and collateral flow were determined by using cerium-141-labeled microspheres (15 microns) during the occlusion. After 30 minutes of occlusion, infarct sizes in placebo versus SOD-treated animals were 45.5 +/- 15.7% vs. 23.8 +/- 15.6% of myocardium at risk (p = 0.007). The corresponding values after 60 minutes of occlusion were 78.6 +/- 9.3% vs. 66.9 +/- 14.6% (p = 0.035). SOD administered after 90 minutes of occlusion did not limit infarct size (88.5 +/- 4.8% vs. 92.3 +/- 5.2%). Twenty-four hours of coronary occlusion resulted in infarction of 92.4 +/- 4.2% of myocardium at risk. (All values are mean +/- SD.) Ventricular fibrillation occurred in only nine pigs distributed equally between SOD and placebo. The results indicate that CuZn SOD has the potential to further improve the myocardial salvage established by reperfusion of an ischemic pig heart territory. However, the narrow time window for limiting infarct size in the pig by reperfusion is not much extended by SOD.
Estimation of daily risk of neonatal death, including the day of birth, in 186 countries in 2013: a vital-registration and modelling-based study
Authors: Shefali Oza, Simon N Cousens, Joy E Lawn
Journal: The Lancet Global Health (2014)

The days immediately after birth are the most risky for human survival, yet neonatal mortality risks are generally not reported by day. Early neonatal deaths are sometimes under-reported or might be misclassified by day of death or as stillbirths. We modelled daily neonatal mortality risk and estimated the proportion of deaths on the day of birth and in week 1 for 186 countries in 2013.We reviewed data from vital registration (VR) and demographic and health surveys for information on the timing of neonatal deaths. For countries with high-quality VR we used the data as reported. For countries without high-quality VR data, we applied an exponential model to data from 206 surveys in 79 countries (n=50,396 deaths) to estimate the proportions of neonatal deaths per day and used bootstrap sampling to develop uncertainty estimates.57 countries (n=122,757 deaths) had high-quality VR, and modelled data were used for 129 countries. The proportion of deaths on the day of birth (day 0) and within week 1 varied little by neonatal mortality rate, income, or region. 1·00 million (36.3%) of all neonatal deaths occurred on day 0 (uncertainty range 0·94 million to 1·05 million), and 2·02 million (73.2%) in the first week (uncertainty range 1·99 million to 2·05 million). Sub-Saharan Africa had the highest risk of neonatal death and, therefore, had the highest risk of death on day 0 (11·2 per 1000 livebirths); the highest number of deaths on day 0 was seen in southern Asia (n=392,300).The risk of early neonatal death is very high across a range of countries and contexts. Cost-effective and feasible interventions to improve neonatal and maternity care could save many lives.Save the Children's Saving Newborn Lives programme.
Cirrhosis mortality and per capita consumption of distilled spirits, United States, 1949-94: trend analysis
Authors: R. Roizen, W. C Kerr, K. M Fillmore
Journal: BMJ (1999)

To describe, evaluate, and suggest interpretations for an observed aggregate-level relation between trends in mortality from cirrhosis and per capita consumption of distilled spirits in the United States.Trend analysis using data on US cirrhosis mortality and per capita alcohol consumption.There is a consistent long-term trend relation between mortality from cirrhosis and per capita consumption of distilled spirits in the United States from 1949 to 1994. Two instances of comparatively sharp drops in the consumption of spirits in the 1940s generated mixed results in predicting changes in cirrhosis mortality.An aggregate-level relation between trends in long-term cirrhosis mortality and the consumption of spirits falls considerably short of establishing a direct causal link between the two for individuals. Moreover, two sharp drops in the consumption of spirits generated only mixed results with respect to the short-term trend in cirrhosis. Nevertheless, the observed relation between the consumption of spirits and cirrhosis mortality merits further investigation.
Measuring inspiratory muscle strength in neuromuscular disease: one test or two?
Authors: N. Terzi, D. Orlikowski, C. Fermanian, M. Lejaille, L. Falaize, A. Louis, J-C. Raphael, B. Fauroux, F. Lofaso
Journal: European Respiratory Journal (2007)

Inspiratory muscle strength monitoring is crucial in patients with neuromuscular disorders. The sniff nasal inspiratory pressure (SNIP) and maximal inspiratory pressure (<i>P</i><sub>I,max</sub>) are usually measured. The present study investigated whether the test yielding the best value at baseline continued to yield the best value during follow-up. The present study included 25 patients with Duchenne muscular dystrophy (DMD) and 61 with myotonic muscular dystrophy (MMD). SNIP and <i>P</i><sub>I,max</sub> were measured at baseline and then annually. At baseline, SNIP was lower than <i>P</i><sub>I,max</sub> in 20 (80%) DMD patients and 32 (52%) MMD patients. During follow-up in DMD patients, changes in the best method always occurred from SNIP to <i>P</i><sub>I,max</sub>. In MMD patients, when SNIP was better than <i>P</i><i><sub>I,max</sub> at baseline, SNIP was usually (88%) better during follow-up, whereas a better <i>P</i><sub>I,max</sub> than SNIP at baseline was frequently (50%) followed by a shift to SNIP.</i> Maximal inspiratory pressure may be sufficient for monitoring inspiratory muscle function in Duchenne muscular dystrophy adults. In myotonic muscular dystrophy, the marked variability in the test yielding the best value at baseline indicates a need for performance of both tests at baseline. However, when sniff nasal inspiratory pressure measurement yields the best value at baseline, using sniff nasal inspiratory pressure alone during follow-up may be appropriate.
Aging, telomeres, and atherosclerosis
Authors: M EDO, V ANDRES
Journal: Cardiovascular Research (2004)

Although the level and pace of population aging display high geographical variability, virtually all countries have been experiencing growth in their elderly population, particularly in developed nations. Because aging is a major risk factor for atherosclerosis and associated disease, it is of up most importance to unravel the molecular mechanisms involved in vascular aging. Telomeres are specialized DNA-protein structures located at the ends of eukaryotic chromosomes whose length is progressively reduced in most somatic cells during aging. It is accepted that telomere exhaustion contributes to organismal ageing at least by impairing cell proliferation and viability. An emerging question is whether telomere erosion contributes to atherosclerosis. Here we discuss recent advances on the molecular control of telomere length in vascular cells, as well as animal and human studies that address the role of telomeres in vascular pathobiology. Although the interrelationships between telomere length and cardiovascular disease appear obvious, a chief question that remains unanswered is whether telomere ablation is cause of vascular injury or a surrogate phenomenon.