tbuckley/cabot-search huggingface dataset:
Transient receptor potential channels mediate the tussive response to prostaglandin E<sub>2</sub>and bradykinin
Authors: Megan Grace, Mark A Birrell, Eric Dubuis, Sarah A Maher, Maria G Belvisi
Journal: Thorax (2012)

<h3>Background</h3> Cough is the most frequent reason for consultation with a family doctor, or with a general or respiratory physician. Treatment options are limited and a recent meta-analysis concluded that over-the-counter remedies are ineffective and there is increasing concern about their use in children. Endogenous inflammatory mediators such as prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) and bradykinin (BK), which are often elevated in respiratory disease states, are also known to cause cough by stimulating airway sensory nerves. However, how this occurs is not understood. <h3>Methods</h3> We hypothesised that the transient receptor potential (TRP) channels, TRPA1 and TRPV1, may have a role as ‘common effectors’ of tussive responses to these agents. We have employed a range of in vitro imaging and isolated tissue assays in human, murine and guinea pig tissue and an in vivo cough model to support this hypothesis. <h3>Results</h3> Using calcium imaging we demonstrated that PGE<sub>2</sub> and BK activated isolated guinea pig sensory ganglia and evoked depolarisation (activation) of vagal sensory nerves, which was inhibited by TRPA1 and TRPV1 blockers (JNJ17203212 and HC-030031). These data were confirmed in vagal sensory nerves from TRPA1 and TRPV1 gene deleted mice. TRPV1 and TRPA1 blockers partially inhibited the tussive response to PGE<sub>2</sub> and BK with a complete inhibition obtained in the presence of both antagonists together in a guinea pig conscious cough model. <h3>Conclusion</h3> This study identifies TRPA1 and TRPV1 channels as key regulators of tussive responses elicited by endogenous and exogenous agents, making them the most promising targets currently identified in the development of anti-tussive drugs.
Abnormalities induced by the mutant gene, lpr. Patterns of disease and expression of murine leukemia viruses in SJL/J mice homozygous and heterozygous for lpr.
Authors: H C Morse, J B Roths, W F Davidson, W Y Langdon, T N Fredrickson, J W Hartley
Journal: The Journal of Experimental Medicine (1985)

SJL/J mice heterozygous or homozygous for the lpr mutation were compared with SJL/J-+/+ mice for longevity, histopathology, antigenic characteristics of lymphocytes and expression of murine leukemia viruses (MuLV). In comparison to +/+ mice, lpr homozygotes had a markedly shortened life span, died with infiltrative pulmonary disease, but little or no renal disease, and expressed high levels of infectious ecotropic MuLV in lymphoid tissues. SJL-lpr/+ mice had a life span intermediate between SJL-+/+ and -lpr/lpr mice, died with lymphomas that histologically resembled the neoplasms of +/+ mice, and sometimes expressed high levels of ecotropic MuLV. The lymphomas of lpr/+ could be transplanted to +/+ recipients in 78% of cases, and continuous in vitro lines were established from some of them. Similar effects on virus expression or lymphoma development were not observed in other strains homozygous or heterozygous for the lpr mutation. These results indicate that the diseases expressed by mice homozygous for the lpr mutation are highly strain-dependent, and that this gene can have an effect in the heterozygous state in SJL mice.
Spontaneous internalization of Class I major histocompatibility complex molecules in T lymphoid cells.
Authors: D B Tse, B Pernis
Journal: The Journal of Experimental Medicine (1984)

A low proportion of T lymphocytes in normal mouse spleen contains small intracytoplasmic vesicles showing Class I MHC molecules. After stimulation in vitro in a mixed lymphocyte reaction or by addition of Con A, the proportion of T cells with such intracytoplasmic vesicles increases progressively and becomes the majority. Labeling with fluorochrome-conjugated antibodies has shown that the vesicles are formed by internalization of molecules from the plasma membrane. The process is spontaneous and does not require cross-linking by antibodies or other ligands; it is selective inasmuch as other molecules (Thy-1 and T200 antigens) are not included and it is specific since it is not performed by other cells such as B lymphoid cells or fibroblasts. On the whole the process shows similarities with the internalization and recycling of other receptors, such as the receptors for different macromolecules of metabolic or informational significance, as seen in other cells. On the other hand, the specificity of Class I MHC mobilization in T lymphoid cells suggest a role for this process which is related to the immune function of these molecules.
Randomized, Double-Blind Trial of Antibiotic Exit Site Cream for Prevention of Exit Site Infection in Peritoneal Dialysis Patients
Authors: Judith Bernardini, Filitsa Bender, Tracey Florio, James Sloand, Linda Palmmontalbano, Linda Fried, Beth Piraino
Journal: Journal of the American Society of Nephrology (2005)

Infection is the Achilles heel of peritoneal dialysis. Exit site mupirocin prevents Staphylococcus aureus peritoneal dialysis (PD) infections but does not reduce Pseudomonas aeruginosa or other Gram-negative infections, which are associated with considerable morbidity and sometimes death. Patients from three centers (53% incident to PD and 47% prevalent) were randomized in a double-blinded manner to daily mupirocin or gentamicin cream to the catheter exit site. Infections were tracked prospectively by organism and expressed as episodes per dialysis-year at risk. A total of 133 patients were randomized, 67 to gentamicin and 66 to mupirocin cream. Catheter infection rates were 0.23/yr with gentamicin cream versus 0.54/yr with mupirocin (P = 0.005). Time to first catheter infection was longer using gentamicin (P = 0.03). There were no P. aeruginosa catheter infections using gentamicin compared with 0.11/yr using mupirocin (P < 0.003). S. aureus exit site infections were infrequent in both groups (0.06 and 0.08/yr; P = 0.44). Peritonitis rates were 0.34/yr versus 0.52/yr (P = 0.03), with a striking decrease in Gram-negative peritonitis (0.02/yr versus 0.15/yr; P = 0.003) using gentamicin compared with mupirocin cream, respectively. Gentamicin use was a significant predictor of lower peritonitis rates (relative risk, 0.52; 95% confidence interval, 0.29 to 0.93; P < 0.03), controlling for center and incident versus prevalent patients. Gentamicin cream applied daily to the peritoneal catheter exit site reduced P. aeruginosa and other Gram-negative catheter infections and reduced peritonitis by 35%, particularly Gram-negative organisms. Gentamicin cream was as effective as mupirocin in preventing S. aureus infections. Daily gentamicin cream at the exit site should be the prophylaxis of choice for PD patients.
Diagnostic scope of and exposure to primary care physicians in Australia, New Zealand, and the United States: cross sectional analysis of results from three national surveys
Authors: Andrew B Bindman, Christopher B Forrest, Helena Britt, Peter Crampton, Azeem Majeed
Journal: BMJ (2007)

<b>Objectives</b> To compare mix of patients, scope of practice, and duration of visit in primary care physicians in Australia, New Zealand, and the United States. <b>Design</b> Comparison of three comparable cross sectional surveys performed in 2001-2. Physicians completed a questionnaire on patients9 demographics, diagnoses, and duration of visit. <b>Setting</b> Primary care practice. <b>Participants</b> 79 790 office visits in Australia, 10 064 in New Zealand, and 25 838 in the US. <b>Main outcome measures</b> Diagnostic codes were mapped to the Johns Hopkins expanded diagnostic clusters. Scope of practice was defined as the number of expanded diagnostic clusters accounting for 75% of all managed problems related to morbidity. Exposure to primary care was calculated from duration of visits recorded by the physician, and reports on rates of visits to primary care for each country. <b>Results</b> In each country, primary care physicians managed an average of 1.4 morbidity related problems per visit. In the US, 46 expanded diagnostic clusters accounted for 75% of problems managed compared with 52 in Australia, and 57 in New Zealand. Correlations in the frequencies of managed health problems between countries were high (0.87-0.97 for pairwise comparisons). Though primary care visits were longer in the US than in New Zealand and Australia, the per capita annual exposure to primary care physicians in the US (29.7 minutes) was about half of that in New Zealand (55.5 minutes) and about a third of that in Australia (83.4 minutes) because of higher rates of visits to primary care in these countries. <b>Conclusions</b> Despite differences in the supply and financing of primary care across countries, many aspects of the clinical practice of primary care physicians are remarkably similar in Australia, New Zealand, and the US.
Complement-mediated inhibition of neovascularization reveals a point of convergence between innate immunity and angiogenesis
Authors: Harald F. Langer, Kyoung-Jin Chung, Valeria V. Orlova, Eun Young Choi, Sunil Kaul, Michael J. Kruhlak, Markella Alatsatianos, Robert A. DeAngelis, Paul A. Roche, Paola Magotti, Xuri Li, Matina Economopoulou, Stavros Rafail, John D. Lambris, Triantafyllos Chavakis
Journal: Blood (2010)
Ventilation-induced neutrophil infiltration depends on nuclear factor-kB and NF-kB repressing factor
Authors: Yi-Ting Lai, Chang-Wei Lin, Chih-Hao Chang, Chung-Yuang Cheng, Wei-Han Lin, Li-Fu Li
Journal: European Respiratory Journal (2013)

Background and objective:  High-tidal-volume mechanical ventilation used in patients with acute lung injury (ALI) can induce the release of inflammatory cytokines, recruitment of neutrophils, and disruption of alveolar epithelial and endothelial barriers. Nuclear factor-kB (NF-kB) and NF-kB repressing factor (NRF) have previously been shown to participate in the regulation of macrophage inflammatory protein-2 (MIP-2) during ALI. However, the mechanisms regulating interactions between mechanical ventilation and NF-kB/NRF remains unclear. We hypothesized that ventilation-induced neutrophil influx and MIP-2 production through activation of NF-kB/NRF pathway.   Methods:  Male C57BL/6 mice were exposed to low-tidal-volume (6 ml/kg) or high-tidal-volume (30 ml/kg) mechanical ventilation using room air with or without 2 mg/kg NF-kB inhibitor SN50 or 6 mg/kg NRF short interfering RNA (siRNA) or 100 mg/kg neutrophil elastase inhibitor administration. Nonventilated mice were used as controls.   Results:  Neutrophil elastase inhibitor ameliorated high-tidal-volume ventilation-induced lung injury, neutrophil influx, production of MIP-2 and malondialdehyde, activation of NF-kB and NRF, and disruption of bronchial microstructure in wild type mice. Mechanical stretch-augmented ALI was also attenuated with pharmacological inhibition of NF-kB activity by SN50 and NRF expression by NRF siRNA.   Conclusions:  Our data suggest that high-tidal-volume mechanical ventilation induces lung injury, neutrophil influx, oxidative stress, and production of MIP-2, at least partly, through activation of NF-kB/NRF pathway.  Sources of Support: NSC 101-2314-B-182A-088-MY3.
Identifying Social Distress: A Cross-Sectional Survey of Social Outcomes 12 to 36 Months After Colorectal Cancer Diagnosis
Authors: Penny Wright, Amy Downing, Eva J.A. Morris, Jessica L. Corner, Mike A. Richards, David Sebag-Montefiore, Paul Finan, Adam W. Glaser
Journal: Journal of Clinical Oncology (2015)

To establish the prevalence and determinants of poor social outcomes after a diagnosis of colorectal cancer (CRC).All 12- to 36-month survivors of CRC (International Classification of Diseases [10th revision] codes C18 to C20) diagnosed in 2010 or 2011 and treated in the English National Health Service were identified and sent a questionnaire from their treating cancer hospital. This included the Social Difficulties Inventory, a 16-item scale of social distress (SD) comprising everyday living, money matters, and self and others subscales, plus five single items. Sociodemographic and clinical data were also collected. Analyses using descriptive statistics, χ(2) tests, and logistic regression models were conducted.Response rate was 63.3% (21,802 of 34,467). Of the 21,802 participants, 17,830 (81.8%) completed all SD items; 2,688 (15.1%) of these 17,830 respondents were classified as experiencing SD (everyday living, 19.5%; money matters, 15.6%; self and others, 18.1%). Multivariable analysis demonstrated having ≥ three long-term conditions was the strongest predictor of SD (odds ratio [OR], 6.64; 95% CI, 5.67 to 7.77 compared with no long-term conditions), followed by unemployment (OR, 5.11; 95% CI, 4.21 to 6.20 compared with being employed), having recurrent or nontreatable disease (OR, 2.75; 95% CI, 2.49 to 3.04 compared with being in remission), and having a stoma (OR, 2.10; 95% CI, 1.86 to 2.36 compared with no stoma). Additional predictors of SD were young age (< 55 years), living in a more deprived area, nonwhite ethnicity, having advanced-stage disease, having undergone radiotherapy, and being a carer.Although it is reassuring a majority do not experience social difficulties, a minority reported significant SD 12 to 36 months after diagnosis of CRC. The identified clinical and social risk factors are easy to establish and should be used to target support.
Eating Disorders in Girls and Women With Type 1 Diabetes: A Longitudinal Study of Prevalence, Onset, Remission, and Recurrence
Authors: Patricia A. Colton, Marion P. Olmsted, Denis Daneman, Jamie C. Farquhar, Harmonie Wong, Stephanie Muskat, Gary M. Rodin
Journal: Diabetes Care (2015)

Girls and women with type 1 diabetes are at increased risk for developing eating disorders (EDs), and these disorders are associated with serious diabetes-related medical complications. This study describes the longitudinal course of disturbed eating behavior (DEB) and EDs in a cohort with type 1 diabetes.A total of 126 girls with type 1 diabetes receiving care for diabetes at The Hospital for Sick Children in Toronto participated in a series of seven interview-based assessments of ED behavior and psychopathology over a 14-year period, beginning in late childhood. Survival analysis was used.Mean age was 11.8 ± 1.5 years at time 1 and 23.7 ± 2.1 years at time 7. At time 7, 32.4% (23/71) met the criteria for a current ED, and an additional 8.5% (6/71) had a subthreshold ED. Mean age at ED onset (full syndrome or below the threshold) was 22.6 years (95% CI 21.6-23.5), and the cumulative probability of onset was 60% by age 25 years. The average time between onset of ED and subsequent ED remission was 4.3 years (95% CI 3.1-5.5), and the cumulative probability of remission was 79% by 6 years after onset. The average time between remission of ED and subsequent recurrence was 6.5 years (95% CI 4.4-8.6), and the cumulative probability of recurrence was 53% by 6 years after remission.In this longitudinal study, EDs were common and persistent, and new onset of ED was documented well into adulthood. Further research regarding prevention and treatment for this vulnerable group is urgently needed.
COMPLICATIONS FOLLOWING ECT OVER A THREE-YEAR PERIOD IN A STATE INSTITUTION
Authors: J. R. MATTHEW, E. CONSTAN
Journal: American Journal of Psychiatry (1964)

Four fatalities are reviewed: 1. Cerebral hemorrhage, 2. Coronary occlusion, 3. Aspiration pneumonia and 4. Pulmonary embolism. Two other complications are also reviewed, one a result of ECT and the other an incidental complication; namely, rupture of an abdominal viscus and acute suppurative appendicitis. Kalinowsky(2) states that coronary complications may arise following ECT. He states that cerebral hemorrhage has not occurred in his experience. Kalinowsky(3) also states intestinal ruptures have occurred as has pulmonary embolism from pelvic thrombosis. Clinically, the occurrence of the described unusual complications following the use of ECT over a 3-year period in one institution has resulted in a broadening of the staff's education and experience in this field and have tested their mettle in coping with these complications. However, in spite of the fact that complications do arise, the value of this form of treatment is in no way disputed.
A prospective study of the incidence of skin cancer and its risk factors in a Spanish Mediterranean population of kidney transplant recipients
Authors: M.J. Fuente, M. Sabat, J. Roca, R. Lauzurica, M.T. Fernandez-Figueras, C. Ferrandiz
Journal: British Journal of Dermatology (2003)

Background Skin cancer is the most common malignancy occurring in kidney transplant recipients (KTRs). Objectives Our purpose was to investigate, prospectively, the cumulative incidence of cancerous and precancerous skin lesions as well as their risk factors in a close follow‐up population of KTRs from a Mediterranean area of Spain. Patients and methods One hundred and seventy‐four consecutive KTRs were examined at the moment of transplant and then at 6‐month intervals. The cumulative incidence of skin cancer was computed. To analyse the role of potential risk factors (age at transplantation, cause of renal failure, duration of pretransplant dialysis, type of immunosuppressive regimen, sun‐reactive skin type and history of occupational sun exposure), the Cox regression method was used. Results After a median follow‐up of 72 months (range, 12–140), 39 patients (25·3%) developed 142 tumours [84 basal cell carcinoma (BCC) and 58 squamous cell carcinoma (SCC)]. The BCC/SCC ratio was 1·4 : 1. The cumulative incidence for skin cancer was 13% after 3 years of graft survival, increasing to 27·5% at 6 years and 48% at 10 years. Only age at the time of transplantation and occupational sun exposure had statistical significance as risk factors (P < 0·001). Conclusions Our study confirms the high incidence of non‐melanoma skin cancer among KTRs in a Mediterranean population with occupational sun exposure and the patient's age at the time of transplantation being the main risk factors. We believe that all organ transplant programs should provide educational information about protecting oneself from the sun as well as include follow‐up visits by dermatologists in order to facilitate early diagnosis and treatment of skin cancer.
Clinical applications of mesenchymal stem cells
Authors: Shihua Wang, Xuebin Qu, Robert Chunhua Zhao
Journal: Journal of Hematology & Oncology (2012)

Abstract Mesenchymal stem cells (MSC) have generated a great amount of enthusiasm over the past decade as a novel therapeutic paradigm for a variety of diseases. Currently, MSC based clinical trials have been conducted for at least 12 kinds of pathological conditions, with many completed trials demonstrating the safety and efficacy. This review provides an overview of the recent clinical findings related to MSC therapeutic effects. Roles of MSCs in clinical trials conducted to treat graft-versus-host-disease (GVHD) and cardiovascular diseases are highlighted. Clinical application of MSC are mainly attributed to their important four biological properties- the ability to home to sites of inflammation following tissue injury when injected intravenously; to differentiate into various cell types; to secrete multiple bioactive molecules capable of stimulating recovery of injured cells and inhibiting inflammation and to perform immunomodulatory functions. Here, we will discuss these four properties. Moreover, the issues surrounding clinical grade MSCs and principles for MSC therapeutic approaches are also addressed on the transition of MSCs therapy from bench side to bedside.
Cerebral Circulatory Effects of Acutely Induced Hypervolemia in Human Subjects
Authors: Seymour Eisenberg
Journal: Circulation Research (1962)

Expansion of the blood volume with 5 per cent albumin solution was associated with a 32 per cent increase in cerebral blood flow and a commensurate decrease in cerebral vascular resistance. Expansion of the intravascular volume with whole blood was not associated with any consistent cerebral hemodynamic alteration. It is suggested that the response of the cerebral circulation was largely governed by the factitious "anemia" induced by the selective expansion of the plasma volume.
ON THE USE OF CERTAIN ANTISEPTIC SUBSTANCES IN THE TREATMENT OF INFECTED WOUNDS
Authors: H. D. Dakin
Journal: BMJ (1915)

IN order to make a jucdicious clhoice of the antiseptic most likely to give useful results in the treatment of infected wounds m:lany different factors lhave to be considered in addition to germicidal activity, including tlle irritating properties of the substances, their toxicity, solubility, ability to penetrate tissues and to be absorbed, and their chemical reactions with proteins and other tissue constituents.The k.illing of bacteria by ordinary antiseptic substances is esseiltially a clhemiical reaction between the antiseptic on the onle lhand and the proteins and other cell constitu'ents of the micro-organism on tlle other.The destruction by auitiseptics of bacteria suspended in water is -easily effected, because no proteins are present in the mixture
The relationship between moisture or mould observations in houses and the state of health of their occupants
Authors: OM Koskinen, TM Husman, TM Meklin, AI Nevalainen
Journal: European Respiratory Journal (1999)

This work was conducted in order to study how the health of adults is affected by the presence of moisture or mould in the home. A random sample of 310 houses in Finland was studied during the years 1993-1994. The houses were investigated for visual signs of moisture by a surveyor, and observations of mould were reported by the occupants. A moisture problem was observed in 52% and a mould problem in 27% of the houses. Health data was collected by means of a postal questionnaire from 699 adults. Exposure to moisture was significantly associated with sinusitis, acute bronchitis, nocturnal cough, nocturnal dyspnoea and sore throat, and the exposed inhabitants had significantly more episodes of common cold and tonsillitis. Exposure to mould was significantly associated with common cold, cough without phlegm, nocturnal cough, sore throat, rhinitis, fatigue and difficulties in concentration. Building-related moisture or mould increased the risk of upper and lower respiratory infections and symptoms as well as of nonrespiratory symptoms.
Henry Fuseli, Nightmare, and Sleep Paralysis
Authors: Jerome M. Schneck
Journal: JAMA (1969)

Henry Fuseli painted "The Nightmare" in 1781 (see cover). The picture is dramatic, and it has been used to illustrate articles in professional journals. I believe the painting has several features of sleep paralysis, and my remarks are so directed. Fuseli was an Anglo-Swiss painter and author, born in Zurich, Feb 7, 1741.<sup>1</sup>His father was Johann Caspar Füssli, a court painter and town clerk. Henry Fuseli was educated at the Collegium Carolinum in Zurich. He started to study theology but left home because of problems stemming from a political publication. He went to Berlin, and then in 1764 to London on the recommendation of the British ambassador. The following year he translated into English J. J. Winckelmann's<i>Reflections on the Painting And Sculpture of the Greeks</i>. In 1770 he went to Italy to become a painter, having been encouraged by Sir Joshua Reynolds. He sent his first work