tbuckley/cabot-search huggingface dataset:
Lessons Learned from Randomized Clinical Trials of Micronutrient Supplementation for Cancer Prevention
Authors: Susan T. Mayne, Leah M. Ferrucci, Brenda Cartmel
Journal: Annual Review of Nutrition (2012)

This review discusses the results of randomized clinical trials of supplemental micronutrients for cancer prevention completed over the past 20 years, including trials of beta-carotene and retinol, vitamins C and E, selenium, folic acid, and vitamin D. Some trials observed significant reductions in risk, whereas others observed significant increases in risk of the primary cancer endpoint. In considering these trials, it appears that supplementation targeted to populations with low status of the nutrient of interest may prevent cancer, whereas supplementation in populations with higher status or to achieve pharmacological exposures may promote cancer. Observational epidemiologic evidence coupled with these trial results supports the concept of a U-shaped curve for micronutrients in relation to cancer prevention. Based on these data, nutrient supplements are not currently recommended for cancer prevention in the general population. The hypothesis that groups with low nutrient status may benefit from supplementation has yet to be formally tested.
Absence of Monocyte Chemoattractant Protein 1 in Mice Leads to Decreased Local Macrophage Recruitment and Antigen-Specific T Helper Cell Type 1 Immune Response in Experimental Autoimmune Encephalomyelitis
Authors: DeRen Huang, Jintang Wang, Pia Kivisakk, Barrett J. Rollins, Richard M. Ransohoff
Journal: The Journal of Experimental Medicine (2001)

Monocyte chemoattractant protein (MCP)-1 plays a critical role in innate immunity by directing the migration of monocytes into inflammatory sites. Recent data indicated a function for this chemokine in adaptive immunity as a regulator of T cell commitment to T helper cell type 2 (Th2) effector function. Studies in a Th1-dependent animal model, experimental autoimmune encephalomyelitis (EAE), showed that MCP-1 was highly expressed in the central nervous system (CNS) of affected rodents, and MCP-1 antibodies could block relapses of the disease. Mice deficient for the major MCP-1 receptor, CC chemokine receptor (CCR)2, did not develop EAE after active immunization but generated effector cells that could transfer the disease to naive wild-type recipients. We analyzed EAE in mice deficient for MCP-1 to define the relevant ligand for CCR2, which responds to murine MCP-1, MCP-2, MCP-3, and MCP-5. We found that C57BL/6 MCP-1-null mice were markedly resistant to EAE after active immunization, with drastically impaired recruitment of macrophages to the CNS, yet able to generate effector T cells that transferred severe disease to naive wild-type recipients. By contrast, adoptive transfer of primed T cells from wild-type mice into naive MCP-1-null recipients did not mediate clinical EAE. On the SJL background, disruption of the MCP-1 gene produced a milder EAE phenotype with diminished relapses that mimicked previous findings using anti-MCP-1 antibodies. There was no compensatory upregulation of MCP-2, MCP-3, or MCP-5 in MCP-1-null mice with EAE. These results indicated that MCP-1 is the major CCR2 ligand in mice with EAE, and provided an opportunity to define the role of MCP-1 in EAE. Compared with wild-type littermates, MCP-1-/- mice exhibited reduced expression of interferon gamma in draining lymph node and CNS and increased antigen-specific immunoglobulin G1 antibody production. Taken together, these data demonstrate that MCP-1 is crucial for Th1 immune responses in EAE induction and that macrophage recruitment to the inflamed CNS target organ is required for primed T cells to execute a Th1 effector program in EAE.
Variation in acute exacerbation rates (AER) of COPD over 5 years
Authors: Ronald Dandurand, Jean Bourbeau, David Eidleman
Journal: European Respiratory Journal (2013)

The previous year’s AER is used to grade COPD severity and is felt to be stable year to year. We wished to evaluate AER variation in our practice. Patients with symptoms compatible with COPD, >10 pack-year smoking history, and a post bronchodilator FEV1/FVC 2 days treated with antibiotics ± prednisone defined exacerbation. Spirometry and COPD Assessment Tests were measured when well. Cumulative average AERs were calculated for each patient. Distribution of the 157 subjects by the old GOLD stage was; I 23 (15%), II 89 (57), III 38 (24), IV 7 (4) and new GOLD grade; A 24 (15), B 59 (38), C 7(4), D 67 (43). Figure 1A shows the number of subjects vs. AER by year. The AERs are stable from year to year for the group as a whole. Figure 1B shows the number of subjects vs. AERs by each patient’s cumulative average AER by year. The AERs are stable in the >3 group and there are changes which plateau by 3 years in the >0≤1, >1≤2 and >2≤3 groups. The 0 group declines progressively.

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This small population data demonstrates fluctuation in AERs from year to year in most patients and the cumulative average AER seems to stabilize by 3 years. Those with AER>3 initially continue to experience this high AER. Only 5% of patients remain exacerbation free by the end of 5 years. These longitudinal observations require validation in larger, more regionally divers populations.

 [1]: pending:yes
Selective involvement of ERK and JNK MAP kinases in the synovial tissue of patients with early arthritis
Authors: D de Launay, M G H van de Sande, G P M van de Sande, C A Wijbrandts, P P Tak, K A Reedquist
Journal: Annals of the Rheumatic Diseases (2010)

BackgroundLittle is known about the contribution of mitogen-activated protein kinase (MAPK) to disease in rheumatoid arthritis (RA), although inhibitors targeting one of these enzymes (p38) have already entered the clinic.We have investigated synovial MAPK activation status in disease-modifying antirheumatic drug (DMARD)-naïve patients with early arthritis.Methods 50 patients with DMARD-naïve early arthritis (disease duration <1 year) were prospectively followed and diagnosed at baseline and after 2 years according to criteria for undifferentiated arthritis (UA), RA or spondyloarthritis (SpA).Synovial biopsies from actively infl amed joints were obtained at baseline by needle arthroscopy and examined by immunohistochemistry for expression and phosphorylation of p38, extracellular signal-regulated kinase 1 and 2 (ERK 1/2) and c-Jun-N-terminal kinase/mitogen-activated protein kinases (JNK/MAPKs) using computer-assisted image analysis.Results were compared between patients with different diagnoses and disease outcomes.Results Activation of ERK was enhanced at inclusion in patients meeting RA criteria after 2 years compared with SpA (p<0.05) and UA (n=6) (p<0.005).JNK activation was significantly higher in RA than in SpA (p<0.005) and UA (p<0.01).p38 activation was similar between diagnostic groups.Logistic regression analysis demonstrated that synovial JNK activation, but not p38 or ERK activation, predicts fulfi lment of RA classifi cation criteria after 2 years (R 2 =0.59, p=0.02).Comparing patients diagnosed with UA at baseline who fulfi lled RA classifi cation criteria after 2 years with those who remained UA, activation of JNK (p<0.005) but not p38 or ERK was signifi cantly enhanced.Activation of ERK (p<0.01) and JNK (p<0.01) at baseline was also enhanced in RA patients with progressive joint destruction as assessed by comparison of x-rays at baseline and after 2 years.Comparing all patients with early arthritis, activation of p38 (p<0.05),ERK (p<0.005) and JNK (p<0.001) was elevated in patients with erosive disease.Conclusions In patients with early arthritis, elevated ERK and JNK activity distinguish RA from other forms of arthritis and JNK activation is already elevated in patients with RA, even before classifi cation criteria of RA are met.Activation of MAPKs is also associated with the development of erosive disease and JNK activation predicts the development of erosive disease in early arthritis patients.Together, our data suggest that strategies targeting ERK and JNK, rather than p38, may be benefi cial in treating RA early in the disease process.on July 7,
Bleeding terminal ileal ulcer
Authors: A Sarkar, K Basu, S S Johal, K Suvarna, K Clout
Journal: Gut (2006)

<h3>Objectives:</h3> To examine priorities for health status improvement in patients with active rheumatoid arthritis (RA) during anti-tumour necrosis factor (TNF) treatment. <h3>Methods:</h3> Data were used from 173 patients with RA starting treatment with TNF-blocking agents. Outcome measures included assessment of health status with the Arthritis Impact Measurement Scales 2 (AIMS2) at baseline and after 3 and 12 months. The AIMS2 contains a priority list from which patients are asked to select from 12 areas of health the 3 in which they would most like to see improvement. <h3>Results:</h3> After 1 year of treatment, 10 out of 12 areas of health on the AIMS2 were significantly improved. The most commonly selected priorities for improvement at baseline were pain (88%), hand and finger function (57%), walking and bending (42%), mobility (33%), and work (29%). At group level, this priority ranking remained largely unchanged during treatment. After adjustment for multiple comparisons, only pain was selected significantly less often at 3 and 12 months (71% at both assessments). Within individual patients, however, priorities often changed. Changes in the priority of pain were related to the achieved level of patient-perceived pain and disease activity. <h3>Conclusions:</h3> This study shows that, at the group level, patients’ priorities for improvement are fairly stable during 12 months of anti-TNF therapy, despite major improvements in health status. Although pain reduction becomes somewhat less important, it remains the most commonly selected priority. In contrast, individual patient priorities are not stable over the course of treatment and appear to be associated with differences in disease state.
Corticosteroid allergy in asthma
Authors: K. Kilpiö, M. Hannuksela
Journal: Allergy (2003)

Glucocorticosteroids form the basis of therapy for asthma and other allergic diseases. However, they frequently cause delayed contact allergy and occasionally immediate allergy. The purpose of this study was to investigate the occurrence of corticosteroid allergy among patients with asthma and with some complaints caused by inhaled corticosteroids.Patch tests with corticosteroids were performed in 51 asthma patients with side-effects from inhalant corticosteroids and in 50 symptom-free asthma patients using the Finn Chamber system. The corticosteroids and their vehicles were: betamethasone-17-valerate 1% in petrolatum, hydrocortisone-17-butyrate (Hc-17-B) 1% in ethanol, tixocortol-21-pivalate 1% in petrolatum, budesonide 0.1% in petrolatum, beclomethasone dipropionate 0.1 and 0.5% in petrolatum and as inhalant powder 200 microg, and fluticasone propionate 0.1 and 0.5% in petrolatum and as inhalant powder 250 microg. The results were read twice, on D4-5 and again on D10.Two patients in the symptomatic group reacted to corticosteroids in patch tests, one to betamethasone-17-valerate, Hc-17-B and budesonide, and the other to budesonide and Hc-17-B. The first patient suffered from widespread eczematous dermatitis when using beclomethasone. Fluticasone caused oropharyngeal irritation, hoarseness and shortness of breath. The second patient experienced a severe rash after the fourth budesonide inhalation. She had used various topical corticosteroids for her atopic dermatitis without any side-effects. None of the symptom-free patients showed positive results.Delayed allergy to corticosteroids occurs occasionally in asthma, perhaps in the same frequency as in dermatitis. A positive patch test reaction usually means clinical allergy, i.e. the patient cannot use that particular steroid. Cross allergy between corticosteroids is common. However, such patients usually tolerate some other common corticosteroids.
Hypocapnia-induced contraction of porcine airway smooth muscle
Authors: KS Lindeman, TL Croxton, B Lande, CA Hirshman
Journal: European Respiratory Journal (1998)

Hypocapnia constricts peripheral airways in vivo. This study investigated the role of airway smooth muscle in this phenomenon and the mechanism of hypocapnia-induced contraction in vitro. Isometric tension, intracellular pH (pHi) and intracellular free calcium concentration ([Ca2+]i) were measured in porcine airway smooth muscles suspended in organ baths in the presence of 5% or 0% CO2. In tracheal strips precontracted with carbachol, hypocapnic challenge (0% CO2) produced increases in tension, pHi, and [Ca2+]i. In bronchial rings or tracheal strips precontracted with carbachol, nifedipine administered between consecutive contractions attenuated responses to hypocapnia (75+/-11% above carbachol-precontracted tension before nifedipine versus 39+/-9% after nifedipine, n=7 bronchial rings, p<0.05). Neither indomethacin (5 microM), nordihydroguaiaretic acid (10 microM) nor phenidone (10 microM) significantly altered responses. These data suggest that enhanced Ca2+ influx through voltage-dependent Ca2+ channels of airway smooth muscle cells is important in airway responses to hypocapnia.
Cancer Incidence and Cancer Mortality in Relation to Serum Cholesterol
Authors: S. A. Tornberg, L.-E. Holm, J. M. Carstensen, G. A. Eklund
Journal: JNCI Journal of the National Cancer Institute (1989)

We studied cancer incidence and mortality from cancer and coronary heart disease in relation to serum cholesterol levels in 92, 710 individuals followed-up in the nationwide Swedish Cancer Register and the Swedish Cause of Death Register for 18–20 years. According to Cox's proportional hazard model, total cancer incidence and total cancer mortality were negatively correlated to serum cholesterol level (P<.001). The negative correlations were most pronounced during the first years of follow-up. Cancer mortality data showed a stronger negative association to cholesterol than did incidence data during the first 10 years of follow-up (P<.05). Mortality from coronary heart disease was positively correlated to serum cholesterol (P<.001) during the entire follow-up. In contrast to most studies that were based on mortality data, our results of the comparison of incidence and mortality data of the same cohort are in agreement with those of a cholesterol-lowering effect of a preclinical cancer. Efforts by investigators and clinicians to lower serum cholesterol to prevent cardiovascular disease are, according to the present findings, not likely to increase cancer mortality risks but would extend life, irrespective of cause of death. [J Natl Cancer Inst 81: 1917–1921, 1989].
Dendritic cell paralysis
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

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Lung DCs that lack IL-12p40 fail to migrate to lymph nodes in response to challenge with Mtb. When airborne bacteria are inhaled into the lungs they are quickly taken up by resident dendritic cells (DCs), which ferry bacterial antigens to the lymph nodes. Once in the
STUDIES ON A NON-HEMOLYTIC STREPTOCOCCUS ISOLATED FROM THE RESPIRATORY TRACT OF HUMAN BEINGS
Authors: George S. Mirick, Lewis Thomas, Edward C. Curnen, Frank L. Horsfall
Journal: The Journal of Experimental Medicine (1944)

The results of studies on the immunological relationship between streptococcus MG and Streptococcus salivarius type I are described. Evidence is presented to show that Streptococcus salivarius type I, like streptococcus MG, possesses a capsular polysaccharide antigen. Similarities in the capsular polysaccharides of these two different species of non-hemolytic streptococci appear to be responsible for their immunological relationship.
Intentional Weight Loss and Death in Overweight and Obese U.S. Adults 35 Years of Age and Older
Authors: Edward W. Gregg, Robert B. Gerzoff, Theodore J. Thompson, David F. Williamson
Journal: Annals of Internal Medicine (2003)

Background: Although weight loss improves risk factors for cardiovascular and metabolic disease, it is unclear whether intentional weight loss reduces mortality rates. Objective: To examine the relationships among intention to lose weight, weight loss, and all-cause mortality. Design: Prospective cohort study using a probability sample of the U.S. population. Setting: Interviewer-administered survey. Participants: 6391 overweight and obese persons (body mass index 25 kg/m2) who were at least 35 years of age. Measurements: Intention to lose weight and weight change during the past year were assessed by self-report in 1989. Vital status was followed for 9 years. Hazard rate ratios (HRRs) were adjusted for age, sex, ethnicity, education, smoking, health status, health care utilization, and initial body mass index. Results: Compared with persons not trying to lose weight and reporting no weight change, those reporting intentional weight loss had a 24% lower mortality rate (HRR, 0.76 [95% CI, 0.60 to 0.97]) and those with unintentional weight loss had a 31% higher mortality rate (HRR, 1.31 [CI, 1.01 to 1.70]). However, mortality rates were lower in persons who reported trying to lose weight than those in not trying to lose weight, independent of actual weight change. Compared with persons not trying to lose weight and reporting no weight change, persons trying to lose weight had the following HRRs: no weight change, 0.80 (CI, 0.65 to 0.99); gained weight, 0.94 (CI, 0.65 to 1.37); and lost weight, 0.76 (CI, 0.60 to 0.97). Conclusions: Attempted weight loss is associated with lower all-cause mortality, independent of weight change. Self-reported intentional weight loss is associated with lower mortality rates, and weight loss is associated with higher mortality rates only if it is unintentional.
Cardiovascular Care in an Increasingly Diverse Community
Authors: Garth N. Graham, Clyde W. Yancy, Amber K. Boehm, Minh H.D. Wendt
Journal: Circulation (2012)

C ardiovascular care in an increas- ingly diverse community represents a distinct challenge for cardiovascular medicine, the following cases illustrate these challenges.Case Presentation: A 66-year-old black woman arrives at her local emergency department in the southern United States.She works as a full-time secretary and has a history of poorly controlled hypertension despite several attempts at combination drug treatment therapies.She presents with chest pain and shortness of breath.Her antihypertensive regimen is adjusted, and she is given a follow-up appointment to see her usual physician.She returns in 2 weeks with new-onset heart failure (HF) status post old acute myocardial infarction.Case Presentation: A 72-year-old Hispanic woman visits her primary care physician.She has previously been diagnosed with diabetes mellitus, hypertension, and kidney disease.She speaks only Spanish, but the translator is not available owing to illness.The patient tells her physician that she has been experiencing shortness of breath and complains of no other symptoms.The patient is given a diuretic and a return appointment.She is admitted 3 days later with decompensated HF.Case Presentation: A 52-year-old stoic Southeast Asian man, a practicing physician, reports to a colleague the sudden onset of chest pain.He has had no previous diagnoses and exhibited no risk factors before the event.He is reassured and a routine exercise treadmill test is ordered.Within 24 hours, he experiences sudden cardiac death.
Heterogeneity of the aggregation response of human platelets to arginine vasopressin
Authors: Neil A. Lachant, Mary R. Smith, Zi‐Jian Xie, William R. Romani, Jane Zhou
Journal: American Journal of Hematology (1995)

Abstract Previous reports have alluded to variability in the aggregation response of normal human platelets to the neuropeptide arginine vasopressin (AVP). Since it has not been well documented, the current studies were undertaken to characterize this response. AVP (1‐100 nM) produced a concentration‐dependent aggregation response. Although the aggregation response to 100 nM AVP did not correlate with age or sex, there was a bimodal response distribution based on the presence or absence of a second wave of aggregation. In kinetic studies, the apparent km of AVP was 18.3 ± 5.4 nM. There was a significant inverse relationship between the maximal aggregation response to 100 nM AVP and the km (r = −0.82). One hundred nanomolar AVP increased the intracellular calcium concentration of platelets by 406 ± 120 nM in calcium free buffer and by 658 ± 233 nM in the presence of 1.0 nM CaCl 2 . The aggregation response to 100 nM AVP correlated most strongly with the transmembrane influx of calcium (r = 0.84). In individuals whom 100 nM AVP was able to generate a second wave of aggregation, the selective protein kinase C inhibitor bis‐indolylmaleimide significantly decreased the platelet aggregation response. Thus, there is significant heterogeneity in the aggregation response of normal human platelets to AVP. Based on our kinetic studies and the effects of PKC inhibition on the aggregation response to AVP, we would hypothesize that the variability of the aggregation response of normal human platelets to AVP is related to a polymorphism of the platelet AVP V 1 receptor. © 1995 Wlley‐Liss, Inc.
Non-adhesive cyanoacrylate as an embolic material for endovascular neurosurgery
Authors: Hisayuki Oowaki, Shojiro Matsuda, Nobuyuki Sakai, Takayuki Ohta, Hiroo Iwata, Akiyo Sadato, Waro Taki, Nobuo Hashimoto, None Yoshito Ikada
Journal: Biomaterials (2000)
Variations in leucocyte count during menstrual cycle.
Authors: B J Bain, J M England
Journal: BMJ (1975)

The neutrophil counts of seven women, three tkaing oral contraceptives and four nottaking them, showed cyclical variations during the menstrual cycle, most consistentlya fall in the neutrophil count at menstuation. The neutrophil count in women not taking oral contraceptives rose to a peak twice during each cycle. One womennot taking oral contraceptives was studied in detail over eight consecutive menstrualcycles. She showed two neutrophil peaks per cycle and a similiar variation in themonocyte count. The eosinophil count showed a reciprocal relation with the neutrophil count and the basophil count fell in mid-cycle. The changes in her neutrophil count seemed to follow changes in oestrogen level with a delay of one to two days. Oestrogen probably promotes release of neutrophils from the bone marrow rather than from the marginated pool.
Breaking bad news: consensus guidelines for medical practitioners.
Authors: A Girgis, R W Sanson-Fisher
Journal: Journal of Clinical Oncology (1995)

PURPOSE AND DESIGN: One of the more difficult tasks that clinicians must perform as part of their care of patients is that of conveying bad news, such as a severe diagnosis or death. However, there is a paucity of empirically founded information that relates to the specific steps for breaking bad news. We report on a set of guidelines for breaking bad news that was developed using a consensus process and incorporates the views of medical oncologists, general practitioners, surgeons, nurse consultants, social workers, clergy, human rights representatives, cancer patients, hospital interns, and clinical directors of medical schools in Australia. RESULTS AND CONCLUSION: It is recommended that further research be undertaken in a number of areas. First, there is a need to assess patients' versus providers' perceptions of the importance of each of the steps in breaking bad news, in order to define criteria for minimal levels of competence in this area. Second, controlled trials are needed to assess the effectiveness of the guidelines in changing clinical practice, and to identify the most effective strategies for breaking bad news to patients.