tbuckley/cabot-search huggingface dataset:
Nanocarriers for Vascular Delivery of Anti-Inflammatory Agents
Authors: Melissa D. Howard, Elizabeth D. Hood, Blaine Zern, Vladimir V. Shuvaev, Tilo Grosser, Vladimir R. Muzykantov
Journal: The Annual Review of Pharmacology and Toxicology (2014)

There is a need for improved treatment of acute vascular inflammation in conditions such as ischemia-reperfusion injury, acute lung injury, sepsis, and stroke. The vascular endothelium represents an important therapeutic target in these conditions. Furthermore, some anti-inflammatory agents (AIAs) (e.g., biotherapeutics) require precise delivery into subcellular compartments. In theory, optimized delivery to the desired site of action may improve the effects and enable new mechanisms of action of these AIAs. Diverse nanocarriers (NCs) and strategies for targeting them to endothelial cells have been designed and explored for this purpose. Studies in animal models suggest that delivery of AIAs using NCs may provide potent and specific molecular interventions in inflammatory pathways. However, the industrial development and clinical translation of complex NC-AIA formulations are challenging. Rigorous analysis of therapeutic/side effect and benefit/cost ratios is necessary to identify and optimize the approaches that may find clinical utility in the management of acute inflammation.
Cardiovascular Events and Investigation in Patients Who Are Awaiting Cadaveric Kidney Transplantation
Authors: John S. Gill, Irene Ma, David Landsberg, Nathan Johnson, Adeera Levin
Journal: Journal of the American Society of Nephrology (2005)

The optimal strategy for cardiovascular (CV) disease surveillance in kidney transplant candidates is uncertain. In this observational study of 604 wait-listed patients in British Columbia, the risk for CV event in diabetic and nondiabetic candidates was 12.7 and 4.5% per year, respectively. CV event rates were relatively constant during the first 3 yr of wait-listing (5.3 to 6.6 per 100 patient-years; 95% confidence interval [CI], 3.7 to 9.3) but rose dramatically during the peritransplantation period (39.6/100 patient-years; 95% CI, 20.6 to 76.1) and remained high throughout the first posttransplantation year (4.0 per 100 patient-years; 95% CI, 2.2 to 7.5). The results of noninvasive cardiac investigations before wait-listing were not predictive of the time to CV event after wait-listing. The practice of surveillance cardiac investigation in wait-listed patients on the basis of ongoing clinical assessment of cardiac risk resulted in fewer investigations (n = 171) than with the recommended practice of periodic screening on the basis of waiting time alone (n = 530) and was not associated with an increased frequency of CV events (CV event rate in patients with and without the recommended frequency of investigation was 9.9 [95% CI, 7.1 to 13.7] and 6.7 [95% CI, 5.2 to 8.7] per 100 patient-years). It is concluded that transplant candidates are at high risk for CV events particularly during the perioperative period. Initial cardiac investigations have limited value in guiding the timing of patient reevaluation after wait-listing. Periodic surveillance cardiac investigation after wait-listing may be unnecessary and requires further study.
Adjuvant Chemotherapy for Non–Small-Cell Lung Cancer: A Fading Effect?
Authors: Benjamin Besse, Thierry Le Chevalier
Journal: Journal of Clinical Oncology (2008)

Non–small-cell lung cancer (NSCLC) is the leading cause of cancer death for men and women in most industrialized countries. Surgery is the primary treatment modality for patients with early-stage operable NSCLC. Approximately half of these patients eventually experience relapse after resection, with a twoto three-fold higher proportion of distant metastases over local recurrences. Five-year survival rates for early-stage NSCLC range from 60% to 70% in stage I, 40% to 50% in stage II, and only 25% to 30% in patients with stage IIIA tumors. The 1995 meta-analysis published by the Non–SmallCell Lung Cancer Collaborative Group suggested an absolute survival advantage at 5 years of 5% with cisplatin-based chemotherapy (hazard ratio [HR] 0.87; 95% CI, 0.74 to 1.02; P .08). However, most of the early trials were small and underpowered. In the late 1990s, larger adjuvant trials were performed, three of which demonstrated a statistically significant survival benefit from cisplatin-based chemotherapy. Absolute 5-year survival differences ranged from 4% to 15% (HR 0.69 to 0.86). In the recently updated individual data-based Medical Research Council meta-analysis and in Lung Adjuvant CisplatinEvaluation(LACE), the5-yearabsolutebenefitwithchemotherapy ranged from 4% to 5.3% (HR 0.87; 95% CI, 0.81 to 0.93; P .0000001; and HR 0.89; 95% CI, 0.82 to 0.96; P .004, respectively). In the updated Medical Research Council metaanalysis, the effect of chemotherapy in addition to surgery versus surgery alone was studied in 8,147 patients (from 30 trials), with a median follow-up of 5.3 years across all trials. In the LACE study, data were pooled from 4,584 patients in five recent randomized adjuvant cisplatin-based chemotherapy trials and reported with a median follow-up of 5.1 years (range, 3.1 to 5.9 years). On the basis of these results, postoperative cisplatin-based chemotherapy is now widely accepted as treatment for patients with NSCLC. In the current issue of the Journal of Clinical Oncology, Strauss et al report mature data from the Cancer and Leukemia Group B (CALGB) trial 9633. They randomly assigned 344 patients who underwent complete resection for stage IB (T2N0) disease to four postoperative cycles of paclitaxel (200 mg/m) and carboplatin (area under the curve 6), the most frequently used doublet chemotherapy for NSCLC in the United States, compared with surgery alone. Although the initial interim analysis for survival was positive and prompted early termination of the study, survival was no longer significantly different between the two arms after a median follow-up of 74 months (HR 0.83; 90% CI, 0.64 to 1.08; P .12. In an unplanned subgroup analysis, a benefit seemed to appear for patients with tumors 4 cm in diameter (HR 0.69; 90% CI, 0.48 to 0.99; P .043). This study highlights several issues.
Schistosomiasis, metriphonate, cholinesterase, and suxamethonium.
Authors: M F James, J M Jewsbury
Journal: BMJ (1978)

relationship between water hardness and cardiovascular mortality.The efficiency of absorption of lipid from the gut is partly dependent on the bile salts.Increasing concentrations of calcium may interfere with the detergent action of the bile salts and with micelle formation.Oral calcium is known to reduce serum lipids1 and increase faecal bile acid and faecal total fat excretion.2Total intake of calcium in hard-water areas may be as much as 20 % higher than intake in soft-water areas.This could explain the observations of Stitt3 and Elwood4 that calcium concentrations in water supplies are negatively correlated with cholesterol levels and cardiovascular mortality.
Histopathological and immunohistochemical assessment of acquired ichthyosis in patients with human T-cell lymphotropic virus type I-associated myelopathy
Authors: S.P. Milagres, J.A. Sanches, A.C.P. Milagres, N.Y.S. Valente
Journal: British Journal of Dermatology (2003)

Background Patients with human T‐cell lymphotropic virus type I (HTLV‐I)‐associated myelopathy frequently display cutaneous alterations such as acquired ichthyosis. Objectives Elucidation of the pattern of acquired ichthyosis in HTLV‐I‐associated myelopathy. Methods Skin fragments from 10 patients with HTLV‐I‐associated myelopathy presenting with acquired ichthyosis were assessed by histopathological and immunohistochemical tests. We used anticytokeratin antibodies related to normal keratinization (K1/K10), and others related to cutaneous conditions such as activation, migration and hyperproliferation of keratinocytes (K6/K16), and involucrin, a precursor protein in the formation of the protein envelope in keratinocytes. For quantification of the proliferating basal and parabasal cells the anti‐Ki‐67 antibody was employed. Results On light microscopy, all skin specimens displayed orthokeratotic hyperkeratosis and hypogranulosis. Three of them presented focal parakeratosis. A slight to moderate perivascular infiltrate of mononuclear lymphocytes was observed in seven cases, three of which showed discrete spongiosis with epidermotropism of lymphocytes. All fragments displayed coexpression of K1, K10 and K16 in the suprabasal layers. Expression of involucrin was also observed in all cases, in the upper spinous and granular layers. Focal expression of K6 was observed in three cases, under a parakeratotic area. The mean number of Ki‐67+ basal and parabasal cells was 3·5 cells per mm, similar to that in control skin. Conclusions In acquired ichthyosis related to HTLV‐I‐associated myelopathy, histopathology revealed orthokeratotic hyperkeratosis and a perivascular inflammatory infiltrate of mononuclear lymphocytes, with areas of parakeratosis and foci of epidermotropism in rare cases. The expression profiles of K1, K10 and involucrin were similar to those in normal skin. The diffuse coexpression of K16 with K1 and K10 throughout the analysed epidermis, as well as the occurrence of restricted areas of parakeratosis expressing K6, indicate the presence of keratinocyte activation with induction of the alternative keratinization pathway, probably dependent on the cytokines liberated by the mononuclear cells of the dermal inflammatory infiltrate infected with HTLV‐I. The absence of acanthosis and of increased cellular kinetics, as shown by the low rate of Ki‐67 antigen expression, allow the inference that the pattern of acquired ichthyosis related to HTLV‐I‐associated myelopathy may be retentional. The observation of foci of parakeratosis expressing K6 in three specimens suggests that, at least in certain areas and in some cases, interference with epidermal differentiation and maturation occurs.
Subtotal Ablation of Parietal Epithelial Cells Induces Crescent Formation
Authors: Eva-Maria Sicking, Astrid Fuss, Sandra Uhlig, Peggy Jirak, Henry Dijkman, Jack Wetzels, Daniel R. Engel, Torsten Urzynicok, Stefan Heidenreich, Wilhelm Kriz, Christian Kurts, Tammo Ostendorf, Jürgen Floege, Bart Smeets, Marcus J. Moeller
Journal: Journal of the American Society of Nephrology (2012)

Parietal epithelial cells (PECs) of the renal glomerulus contribute to the formation of both cellular crescents in rapidly progressive GN and sclerotic lesions in FSGS. Subtotal transgenic ablation of podocytes induces FSGS but the effect of specific ablation of PECs is unknown. Here, we established an inducible transgenic mouse to allow subtotal ablation of PECs. Proteinuria developed during doxycycline-induced cellular ablation but fully reversed 26 days after termination of doxycycline administration. The ablation of PECs was focal, with only 30% of glomeruli exhibiting histologic changes; however, the number of PECs was reduced up to 90% within affected glomeruli. Ultrastructural analysis revealed disruption of PEC plasma membranes with cytoplasm shedding into Bowman's space. Podocytes showed focal foot process effacement, which was the most likely cause for transient proteinuria. After >9 days of cellular ablation, the remaining PECs formed cellular extensions to cover the denuded Bowman's capsule and expressed the activation marker CD44 de novo. The induced proliferation of PECs persisted throughout the observation period, resulting in the formation of typical cellular crescents with periglomerular infiltrate, albeit without accompanying proteinuria. In summary, subtotal ablation of PECs leads the remaining PECs to react with cellular activation and proliferation, which ultimately forms cellular crescents.
CD3 ζ defects in systemic lupus erythematosus
Authors: Tsutomu Takeuchi, Katsuya Suzuki, Tsuneo Kondo, Keiko Yoshimoto, Kensei Tsuzaka
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Abstract</h3> <h3>Background</h3> All living things speak chemical. The challenge is to discover the vocabulary, the volatile odorant chemicals that enable communication across phylogenies and to translate them to physiological, behavioural and ecological function. Olfactory receptors (ORs) interface animals with airborne odorants. Expression of single ORs in human embryonic kidney cells (HEK-293) makes it possible to interrogate ORs with synthetic chemicals and to identify cognate ligands that convey olfactory information. <h3>Results</h3> The cosmopolitan strain of the vinegar fly <i>Drosophila melanogaster</i> has accompanied the human expansion out of Africa, more than ten thousand years ago. These flies are strictly anthropophilic and depend on human resources and housing for survival, particularly in colder climate zones. Curiously, humans sense the scent of a single fly, and more precisely the female pheromone (Z)-4 undecenal (Z4-11Al), at 10 ng/mL (0.06 µmol/L). A screening of all functional human ORs in a HEK-293 assay provides an explanation for this astounding sensitivity, as it shows that OR10A6, one of the most highly expressed human ORs, is specifically tuned to Z4-11Al. Chemical analysis of fly effluvia confirms that cosmopolitan <i>D. melanogaster</i> females release Z4-11Al, while females of an African fly strain from Zimbabwe release a 1:3-blend of Z4-11Al and (Z)-4 nonenal (Z4-9Al). Interestingly, a blend of Z4-9Al and Z4-11Al produces a different aroma than the the single compounds, which is why we readily differentiate cosmopolitan and Zimbabwe flies by nose. <h3>Conclusion</h3> That we sensitively and specifically perceive the fly pheromone Z4-11Al suggests that it is a component of human odour scenes. This may have afforded a sensory drive during adaptation of commensal flies to human habitats and selected for a role of Z4-11Al in fly aggregation and premating communication. Screening ORs for key ligands leads to the discovery of messenger chemicals that enable chemical communication among and betwen vertebrate and invertebrate animals.
Efficiency of the endo-bronchial volum reduction treatment for heterogeneous lower lobe predominant emphysema
Authors: Turhan Ece, Aysen Erer, Zuleyha Bingol
Journal: European Respiratory Journal (2011)

Background:  Patients with severe chronic obstructive pulmonary disease (COPD) have limited treatment options. Exercise capacity and health related quality of life (HRQL) of these patients are affected by the progress of respiratory failure. Thus, there is a need for new treatments that can palliate. Endo-bronchial volum reduction treatment (EBVRT) which is a minimally invasive method has been come up. Endobronchial valves (EBV) that allow air to escape from a pulmonary lobe but not enter. It can induce a reduction in lobar volume that may thereby improve lung function and exercise tolerance in patients with advanced emphysema.   Method:  To evaluate the safety and effectiveness of the EBVRT of lower lobe predominant heterogeneous emphysema. Functional capacity was evaluated with spirometry, 6minute walk distance (6MWD). SGRQ were applied to evaluate the HRQL.   Result:  Five patients with heterogeneous lower lobe predominant emphysema (two left, three right lower lobe) were treated with EBV. Most of the patients were male (80%). The mean age was 65 years. Valves were placed into left lower lobe (n=2) and right lower lobes (n=3). Valves were placed in airways with 100% technical success. There were no procedure-related deaths and complications. At the third month, there was an increase of 4.6% in the forced expiratory volume 1 second (FEV1) and 2.3% increase of 6MWD were observed. Also, there was a decrease of 2.3% in the SGRQ score was observed.   Conclusion:  EBVRT for heterogeneous lower lobe predominant emphysema patients induced modest improvements in lung function, exercise tolerance, and HRQL. EBVRT is a new safety method for the patients with severe COPD.
Eosinophil cationic protein in children with respiratory allergies – When is it useful?
Authors: Slavica Dodig, Miljenko Raos, Ivan Pavić, Renata Zrinski
Journal: European Respiratory Journal (2011)

Backgrounds:  Eosinophil cationic protein (ECP) is a secretory protein that is released from eosinophils in patients with allergic diseases. The aim of the present study was to investigate the usefulness of determination of serum ECP levels in children with respiratory allergies. Specific objectives were: (1) to asses if there are any differences in serum ECP concentrations between treated and untreated children with asthma, children with rhinitis, and children with both astma and rhinitis and (2) if the natural seasonal exposure to sensitizing allergens is responsible for increasing serum ECP.   Methods:  The study included treated (N=156) and untreated (N=55) children with asthma, children with rhinitis, and children with both, astma and rhinitis. Serum ECP was measured in serum collected between 8:00 and 12:00 a.m. under standardized preanalytical conditions (regarding the type of blood collection tube, time and incubation temperature during blood clotting).   Results:  Untreated children, had significantly higher (p   Conclusions:  If all limiting factors for reliable determination of serum ECP should be taken into account, determination of ECP could be helpful in objective evaluation of eosinophil degranulation in allergic inflammation and for monitoring the effectiveness of anti-inflammatory treatment.
Do persistent perfusion defects predict late recurrences in pulmonary embolism
Authors: Liliana Villari, Roberta Pancani, Letizia Marconi, Elena Mariancini, Ferruccio Aquilini, Alessandro Celi, Antonio Palla
Journal: European Respiratory Journal (2014)

Background : Predicting the risk of recurrence after a first episode of pulmonary embolism (PE) is important to decide the optimal duration of therapy. The significance of persistent perfusion defects as assessed at follow-up lung scans is not known.

Aim : To investigate the persistence of perfusion defects after an episode of PE and its potential role in predicting PE recurrence.

Patients and methods : Perfusion scans of patients with a diagnosis of symptomatic PE between April 2005 and May 2010 with a follow-up of at least 6 months were retrospectively analyzed. Lung scans were read by two physicians and the interobserver agreement analyzed by the Kappa test. Recurrences were defined as the appearance of segmental perfusion defects not present in previous scans.

Results : A 6 months or longer follow-up was available in 252 patients diagnosed with PE. The Kappa statistic ranged from .84 to .98 at different controls. The number of non perfused segments went from 5.8±2.8 at baseline (mean±SD) to 2.1+2.0 at 6 months (p<.001 by ANOVA) to 1.7±1.8 (NS) at 12 months.

After the first month of follow-up, 16 recurrences were recorded. The number of non perfused segments at the last follow-up scan available prior to the recurrence in these 16 patients did not differ from the number of non perfused segments at the six month scan in the patients that did not show a recurrence (1.8;3.1 vs. 1.8;3.4 respectively;median;interquartile range).

Conclusions : after 6 months from an acute event of PE a significant reduction of the number of non perfused segments is observed; this number does not change significantly over the next months. In this series, the persistence of perfusion defects does not predict recurrence of PE.
Bisphenol A in food cans: an update.
Authors: W C Hoyle, R Budway
Journal: Environmental Health Perspectives (1997)

Bisphenol A in Food Cans: An UpdateThe can manufacturing industry and suppliers have followed closely the current research on can coatings and have conducted our own research as it relates to poten- tial exposure to bisphenol A from can coat- ings.We would like to present new research findings that will amend several conclusions drawn by Nagel et al. (1) in Environmental Health Perspectives.The paper states that the active level of bisphenol A in rodents was measured at 2 and 20 micrograms per kilogram body weight per day (jg/kg/day) and is "near or within the reported ranges of human expo- sure."This conclusion appears to be based on human exposure data derived from a paper by Brotons et al. (2) in Environmental Health Perspectives in 1995.New, updated data based on much more definitive analytical methodology supersedes this finding.In late 1996, our industry's Epoxy Can Coating Work Group of the Interindustry Group on Bisphenol A and Alkylphenolscompleted a second study on potential human exposure to bisphenol A from epoxy lacquer-coated food cans.The first study from this work group (3), completed in 1995, was referenced by Nagel et al. (1).The second study was undertaken using the improved analytical methodology that minimizes the interferences which were observed in the first study and likely occurred in the study of Brotons et al. (2).The findings of the 1996 report, "Potential Exposure to Bisphenol A from Epoxy Can Coatings" (4), provide new improved exposure data.This 1996 study with more accurate data was not referenced by Nagel et al. (1).These new data, which have now been provided to the U.S. Food and Drug Administration and the National 1. . .
Intravascular lymphomatosis presenting with a conus medullaris syndrome mimicking disseminated encephalomyelitis
Authors: Stefan Schwarz, Saida Zoubaa, Michael Knauth, Clemens Sommer, Brigitte Storch-Hagenlocher
Journal: Neuro-Oncology (2002)

We describe the clinical, radiologic, and postmortem findings of a 42-year-old man with intravascular lymphomatosis. The patient presented with a conus medullaris syndrome followed by progressive, disseminated spinal and cerebral symptoms. Disseminated encephalomyelitis was suspected due to the clinical, radiologic, and cerebrospinal fluid findings and the results of a stereotactic brain biopsy, all of which were compatible with inflammatory CNS disease. Treatment with methylprednisolone and cyclophosphamide led to a temporary remission of symptoms. The patient died 13 months after onset of symptoms. The diagnosis of disseminated intravascular lymphomatosis was established after death.
Individual Canine Airways Responsiveness to Aerosol Histamine and Methacholine <i>in Vivo</i>
Authors: ROBERT H. BROWN, JAMES GEORGAKOPOULOS, WAYNE MITZNER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Inhalational challenges to histamine and methacholine (Mch) are commonly used to measure airway reactivity. In this study, we investigated the serial distribution of individual airway responsiveness in vivo following stimulation with histamine or methacholine by directly measuring airway area with high resolution computed tomography (HRCT). Anesthetized dogs were challenged on separate days to increasing aerosol concentrations of histamine or Mch. Airway areas of 13 or 14 individual airways in each dog ranging in size from 1.1 to 16.9 mm in diameter at baseline were measured. Dose response curves for each agonist showed a similar responsiveness to each agonist over all airway sizes measured. There was a slightly greater individual airway responsiveness to Mch throughout the airway tree, and this greater responsiveness was also present in those airways that are responsible for the decreased Cdyn observed with Mch challenge. We conclude that in vivo aerosol challenges with histamine or methacholine do not lead to preferential construction of large or small airways.