tbuckley/cabot-search huggingface dataset:
Washing plastic spacers in household detergent reduces electrostatic charge and greatly improves delivery
Authors: F Pierart, JH Wildhaber, I Vrancken, SG Devadason, PN Le Souef
Journal: European Respiratory Journal (1999)

Ionic detergents reduce electrostatic charge on plastic spacers, thereby improving in vitro drug delivery. The aim of this study was to gain practical information on the use of detergents and to evaluate the relevance of this information on in vivo drug deposition. Measurement of electrostatic charge and salbutamol particle size distribution was carried out on detergent-coated and noncoated plastic spacers. The efficiency of four household detergents was compared, and the influence of dilution and the duration of the antistatic effect were studied. In addition, the level of radiolabelled salbutamol deposition in the lungs of eight healthy adults was compared after inhalation through a new versus a detergent-coated spacer. In vitro, all tested detergents reduced the electrostatic charge on the spacer surface. This resulted in a mean increase of 37.4% (range 33.5-41.2) in small particle (&lt;6.8 microm) salbutamol output compared with water-rinsed/drip-dried spacers. Dilution had no influence on the results and the effect lasted for at least four weeks. In vivo, the mean lung deposition of radiolabelled salbutamol in healthy subjects was 45.6% (range 43.4-49.5) through a detergent-coated spacer compared to 11.5% (range 7.6-17.9) through a static spacer (p&lt;0.001). In conclusion, household detergents offer a simple and practical solution to the problem of static on plastic spacers and significantly improve both in vitro and in vivo delivery of salbutamol.
Severe pulmonary complications in Japanese patients after bortezomib treatment for refractory multiple myeloma
Authors: Shigesaburo Miyakoshi, Masahiro Kami, Koichiro Yuji, Tomoko Matsumura, Masaaki Takatoku, Makoto Sasaki, Hiroto Narimatsu, Takeshi Fujii, Masateru Kawabata, Shuichi Taniguchi, Keiya Ozawa, Kazuo Oshimi
Journal: Blood (2006)
Should White-Coat Hypertension in Diabetes Be Treated? Pro
Authors: Giuseppe Mancia, Roberto Sega, Michele Bombelli, Fosca Quarti-Trevano, Rita Facchetti, Guido Grassi
Journal: Diabetes Care (2009)

White coat hypertension, which should be more descriptively termed “isolated clinic hypertension” (1), consists of a condition in which clinic (or office) blood pressure is repeatedly ≥140 mmHg systolic or 90 mmHg diastolic, whereas 24-h mean blood pressure is below its generally accepted upper limit of normality, i.e., <125/80 mmHg (1,2). This article will first show evidence from the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) population study that isolated clinic hypertension is associated with a prevalence of organ damage and a risk of cardiovascular morbidity and mortality, which, although less than those of patients with in- and out-of-office hypertension, are distinctly greater than those displayed by truly normotensive subjects. It will then emphasize that in diabetic subjects, limited evidence is available on the prevalence of isolated clinic hypertension as well as on its association with diabetic-related microvascular and macrovascular disease. In this context, some specific difficulties exist, i.e., 1 ) the uncertainty about whether the cut-off clinic and ambulatory blood pressure values to use should (or should not) be different from those used in nondiabetic individuals, 2 ) the small number of subjects and events in the few studies that have addressed this issue, and 3 ) the confounding effect of factors such as the duration of diabetes, the extent and type of blood pressure–lowering treatments, and the more or less effective blood glucose control when subjects with and without isolated clinic hypertension are compared.

It will be concluded, however, that recommendations on this matter should take into due account that, in diabetes, cardiovascular and renal protection are enhanced by aggressive reductions in clinic blood pressure (<130/80 mmHg) and that lowering blood pressure is beneficial even when the initial clinic value is within the normal blood pressure range, i.e., 130–139 mmHg (2). This scores in favor of a systematic blood …
The turnover and shedding of epithelial cells: Part I The turnover in the gastro-intestinal tract
Authors: B. Creamer, R. G. Shorter, J. Bamforth
Journal: Gut (1961)

This paper confirms that the epithelial lining of the small intestine is in a state of continuous replacement and demonstrates that the whole of the gastrointestinal epithelium has a similar dynamic equilibrium.
B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells
Authors: Tom A. Barr, Ping Shen, Sheila Brown, Vicky Lampropoulou, Toralf Roch, Sarah Lawrie, Boli Fan, Richard A. O’Connor, Stephen M. Anderton, Amit Bar-Or, Simon Fillatreau, David Gray
Journal: The Journal of Experimental Medicine (2012)

B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly understood. We demonstrate that BCDT alleviates central nervous system autoimmunity through ablation of IL-6–secreting pathogenic B cells. B cells from mice with experimental autoimmune encephalomyelitis (EAE) secreted elevated levels of IL-6 compared with B cells from naive controls, and mice with a B cell–specific IL-6 deficiency showed less severe disease than mice with wild-type B cells. Moreover, BCDT ameliorated EAE only in mice with IL-6–sufficient B cells. This mechanism of pathogenesis may also operate in multiple sclerosis (MS) because B cells from MS patients produced more IL-6 than B cells from healthy controls, and this abnormality was normalized with B cell reconstitution after Rituximab treatment. This suggests that BCDT improved disease progression, at least partly, by eliminating IL-6–producing B cells in MS patients. Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell–driven pathogenesis in T cell–mediated autoimmune disease such as EAE and MS.
Functional characteristics of macrophages in patients with acute liver failure
Authors: Richard J. Aspinall
Journal: Hepatology (2013)

Antoniades et al.1 are to be congratulated on their extensive study of intrahepatic and circulating macrophage populations in patients with acetaminophen-induced acute liver failure (ALF). However, their important findings deserve clarification. The authors hypothesize two phases of macrophage involvement during ALF with an influx of bone marrow-derived monocytes being followed by expansion of Kupffer cell-derived macrophages. They compare patients according to clinical outcomes (spontaneous survival, liver transplantation, or death) and describe differing macrophage populations and associated cytokines in each group. However, there are unstated variables that may have influenced their findings. As a tertiary referral center, the authors' patients may receive initial management elsewhere, which could have included empirical antimicrobials. This data should be included, specifically referencing time from overdosage to inclusion in the study rather than timing from admission at the tertiary unit. Furthermore, despite many ALF patients having a documented episode of microbial infection during their illness,2 this group was specifically excluded. This makes it harder to extrapolate the authors' findings to unselected patients with ALF. Most surprisingly, no data are presented regarding ammonia levels in the different outcome scenarios. The authors' group previously reported significant associations between severity of hyperammonemia and progression of encephalopathy in ALF.3 In the current study, both the transplanted patients and those who died displayed more encephalopathy, acidosis, coagulopathy, and elevated proinflammatory cytokines than survivors and are likely to have had hyperammonemia. If so, this has major implications for macrophage functioning in ALF. Clinically relevant concentrations of ammonia sensitize macrophages to activating stimuli, increasing the secretion of proinflammatory cytokines in response to lipopolysaccharide and/or interferon gamma.4 Therefore, it would be valuable to know whether the patient groups studied by Antoniades et al. had different degrees of hyperammonemia. Finally, it should be stated whether patients received extracorporeal liver support or albumin dialysis, as this influences cytokine profiling.5 In summary, Antoniades et al. provide a comprehensive description of macrophage populations in ALF but the clinical relevance of their findings would be enhanced by clarifying patient phenotypes. RICHARD J. ASPINALL, MBCHB, PH.D. Gastroenterology & Hepatology, Queen Alexandra Hospital, Portsmouth, U.K.
Bilateral Hypoperfusion Retinopathy
Authors: A H Dahlmann, D Mccormack, R J Harrison
Journal: Journal of the Royal Society of Medicine (2001)

Hypoperfusion retinopathy, also known as venous stasis or slow flow retinopathy, is a severe and blinding manifestation of carotid artery disease. Treatment by carotid endarterectomy, combined with panretinal photocoagulation, can stabilize vision.
Learning to love big brother
Authors: P McCrory
Journal: British Journal of Sports Medicine (2006)

Apologies to George Orwell but the Evidence Based gurus have replaced the Thought Police. The Ministry of Love has been taken over by the Cochrane Collaboration. Perhaps it is just as well! The latest piece of research to cross my desk creates some food for thought.

One area of sports medicine that has slipped under the radar is podiatry, where practitioners prescribe orthoses on the …
Gene expression and network-based analysis reveals a novel role for hsa-miR-9 and drug control over the p38 network in glioblastoma multiforme progression
Authors: Rotem Ben-Hamo, Sol Efroni
Journal: Genome Medicine (2011)

Glioblastoma multiforme (GBM) is the most common, aggressive and malignant primary tumor of the brain and is associated with one of the worst 5-year survival rates among all human cancers. Identification of molecular interactions that associate with disease progression may be key in finding novel treatments.Using five independent molecular and clinical datasets with a set of computational algorithms we were able to identify a gene-gene and gene-microRNA network that significantly stratifies patient prognosis. By combining gene expression microarray data with microRNA expression levels, copy number alterations, drug response and clinical data, combined with network knowledge, we were able to identify a single pathway at the core of glioblastoma.This network, the p38 network, and an associated microRNA, hsa-miR-9, facilitate prognostic stratification. The microRNA hsa-miR-9 correlated with network behavior and presents binding affinities with network members in a manner that suggests control over network behavior. A similar control over network behavior is possible through a set of drugs. These drugs are part of the treatment regimen for a subpopulation of the patients that participated in the TCGA study and for which the study provides clinical information. Interestingly, the patients that were treated with these specific sets of drugs, all of which targeted against p38 network members, demonstrate highly significant stratification of prognosis.Combined, these results call for attention to p38 network targeted treatment and present the p38 network-hsa-miR-9 control mechanism as critical in GBM progression.
Blood Levels of Organochlorine Residues and Risk of Breast Cancer
Authors: M. S. Wolff, P. G. Toniolo, E. W. Lee, M. Rivera, N. Dubin
Journal: JNCI Journal of the National Cancer Institute (1993)

Organochlorines such as DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and PCBs (polychlorinated biphenyls), which have been used extensively as insecticides and as fluid insulators of electrical components, respectively, are known to be persistent environmental contaminants and animal carcinogens. These agents have been found in human tissue due to their inefficient metabolism and their solubility in lipids, which lead to lifelong sequestration in adipose tissue. Their association with human cancer occurrence, however, has been explored only marginally, with most studies having 20 or fewer cases.This blinded study was designed to determine whether exposure to PCBs and to DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene], the major metabolite of DDT, is associated with breast cancer risk in women.We analyzed sera from the stored blood specimens of 14,290 participants enrolled between 1985 and 1991 in the New York University Women's Health Study, a prospective cohort study of hormones, diet, and cancer. Cohort members who developed breast cancer were included as case patients in our nested case-control study. DDE and PCBs were measured by gas chromatography in the sera of 58 women with a diagnosis of breast cancer 1-6 months after they entered the cohort and in 171 matched control subjects from the same study population who did not develop cancer.Mean levels of DDE and PCBs were higher for breast cancer case patients than for control subjects, but paired differences were statistically significant only for DDE (P = .031). After adjustment for first-degree family history of breast cancer, lifetime lactation, and age at first full-term pregnancy, conditional logistic regression analysis showed a fourfold increase in relative risk of breast cancer for an elevation of serum DDE concentrations from 2.0 ng/mL (10th percentile) to 19.1 ng/mL (90th percentile). For PCBs, the relative risk for a change in serum levels from 3.9 ng/mL (10th percentile) to 10.6 ng/mL (90th percentile) was less than twofold, a nonsignificant association that was further reduced after adjustment for DDE.In this population of New York City women, breast cancer was strongly associated with DDE in serum but not with PCBs.These findings suggest that environmental chemical contamination with organochlorine residues may be an important etiologic factor in breast cancer. Given the widespread dissemination of organochlorine insecticides in the environment and the food chain, the implications are far-reaching for public health intervention worldwide.
INFECTIOUS AGAMMAGLOBULINEMIA: TRANSMISSION OF IMMUNODEFICIENCY WITH GRAFTS OF AGAMMAGLOBULINEMIC CELLS
Authors: R. Michael Blaese, Paul L. Weiden, Irma Koski, Nancy Dooley
Journal: The Journal of Experimental Medicine (1974)

Agammaglobulinemia induced in chickens by surgical bursectomy and irradiation at hatching is transmissible at 4 mo of age to sublethally irradiated normal chickens by bone marrow transplantation. The immunodeficiency which develops in the recipients persists for life and is characterized by inability to produce antibody and by progressive loss of detectable serum IgM and IgG.
Epinephrine Is Required for Normal Cardiovascular Responses to Stress in the Phenylethanolamine N-Methyltransferase Knockout Mouse
Authors: Xuping Bao, Chuanyi M. Lu, Fujun Liu, Yusu Gu, Nancy D. Dalton, Bo-Qing Zhu, Elyse Foster, Ju Chen, Joel S. Karliner, John Ross, Paul C. Simpson, Michael G. Ziegler
Journal: Circulation (2007)

Background— Epinephrine (EPI) is an important neurotransmitter and hormone. Its role in regulating cardiovascular function at rest and with stress is unclear, however. Methods and Results— An epinephrine-deficient mouse model was generated in which the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase was knocked out (KO). Blood pressure and heart rate were monitored by telemetry at rest and during graded treadmill exercise. Cardiac structure and function were evaluated by echocardiography in mice under 1 of 2 conditions: unstressed and lightly anesthetized or restrained and awake. In KO mice, resting cardiovascular function, including blood pressure, heart rate, and cardiac output, was the same as that in wild-type mice, and the basal norepinephrine plasma level was normal. However, inhibition of sympathetic innervation with the ganglion blocker hexamethonium caused a 54% smaller decrease in blood pressure in KO mice, and treadmill exercise caused an 11% higher increase in blood pressure, both suggesting impaired vasodilation in KO mice. Interestingly, phenylethanolamine N-methyltransferase KO did not change the heart rate response to ganglionic blockade and exercise. By echocardiography, KO mice had an increased ratio of left ventricular posterior wall thickness to internal dimensions but did not have cardiac hypertrophy, suggesting concentric remodeling in the KO heart. Finally, in restrained, awake KO mice, heart rate and ejection fraction remained normal, but cardiac output was significantly reduced because of diminished end-diastolic volume. Conclusion— Our data suggest that epinephrine is required for normal blood pressure and cardiac filling responses to stress but is not required for tachycardia during stress or normal cardiovascular function at rest.
Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?
Authors: Lidwien A.M. Smit, David P. Strachan, Roel Vermeulen, Paul I.W. de Bakker, Florence Demenais, Orianne Dumas, Anne-Elie Carsin, Paul Cullinan, Ivan Curjuric, Rebecca E. Ghosh, Dick Heederik, Medea Imboden, Deborah Jarvis, Mark Lathrop, Nicole Le Moual, Amar Mehta, David Miedinger, Torben Sigsgaard, Valérie Siroux, David Vernez, Jan Paul Zock, Francine Kauffmann, Nicole Probst-Hensch, Manolis Kogevinas, Emmanuelle Bouzigon
Journal: European Respiratory Journal (2014)

Recently, a locus centred on rs9273349 in the HLA-DQ region emerged from genome-wide association studies of adult-onset asthma. We aimed to further investigate the role of human leukocyte antigen (HLA) class II in adult-onset asthma and a possible interaction with occupational exposures. We imputed classical HLA-II alleles from 7579 single-nucleotide polymorphisms in 6025 subjects (1202 with adult-onset asthma) from European cohorts: ECRHS, SAPALDIA, EGEA and B58C, and from surveys of bakers and agricultural workers. Based on an asthma-specific job–exposure matrix, 2629 subjects had ever been exposed to high molecular weight (HMW) allergens. We explored associations between 23 common HLA-II alleles and adult-onset asthma, and tested for gene–environment interaction with occupational exposure to HMW allergens. Interaction was also tested for rs9273349. Marginal associations of classical HLA-II alleles and adult-onset asthma were not statistically significant. Interaction was detected between the DPB1*03:01 allele and exposure to HMW allergens (p = 0.009), in particular to latex (p = 0.01). In the unexposed group, the DPB1*03:01 allele was associated with adult-onset asthma (OR 0.67, 95%CI 0.53–0.86). HMW allergen exposures did not modify the association of rs9273349 with adult-onset asthma. Common classical HLA-II alleles were not marginally associated with adult-onset asthma. The association of latex exposure and adult-onset asthma may be modified by DPB1*03:01 .
Needs and Opportunities for Research in Hypersensitivity Pneumonitis
Authors: Jordan N. Fink, Hector G. Ortega, Herbert Y. Reynolds, Yvon F. Cormier, Leland L. Fan, Teri J. Franks, Kathleen Kreiss, Steven Kunkel, David Lynch, Santiago Quirce, Cecile Rose, Robert P. Schleimer, Mark R. Schuyler, Moises Selman, Douglas Trout, Yasuyuki Yoshizawa
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Section:ChooseTop of pageAbstract <<DISEASE DEFINITIONCURRENT CHALLENGES IN EST...HYPERSENSITIVITY PNEUMONI...OCCUPATIONAL AND ENVIRONM...RADIOLOGICAL APPROACHHISTOPATHOLOGICAL ASSESSM...ANIMAL MODELSCHALLENGES AND OPPORTUNIT...RECOMMENDATIONSWORKSHOP PARTICIPANTSReferencesCITING ARTICLES
The Role of Community-based and Philanthropic Organizations in Meeting Cancer Patient and Caregiver Needs
Authors: R. A. Shelby, K. L. Taylor, J. F. Kerner, E. Coleman, D. Blum
Journal: CA A Cancer Journal for Clinicians (2002)

We examined information from community-based and philanthropic organizations to document the cancer-related services that are currently available, establish which services are still needed, and determine who utilizes these formal support networks. In Phase I, 32 of 41 eligible organizations participated in a survey conducted from December 1999 to March 2000. The most common mission focus among participating organizations was information/referral-centered. The most common services provided were referrals to information resources and provision of cancer-related information. Only two of the organizations in Phase I provided client demographic information and both indicated that client populations were predominantly white, female, and over age 40. Phase II of the study involved analyzing patient data from Cancer Care, Inc., a national service organization for cancer patients. Between 1983 and 1997, there were 2,714 prostate cancer patients and 9,451 breast cancer patients included in the Cancer Care database. Their most commonly reported problems were related to personal adjustment to illness, financial, home care, and transportation needs. There were significant differences in problems reported depending upon age and disease status. In addition, the results of this study support the idea that those at highest risk for developing and dying of cancer are the least likely to utilize formal support networks. Further, a gap in service provision for assistance with practical needs (e.g., transportation, home care, child care, psychosocial support) was identified. Due to the increasing use of outpatient care for cancer patients, a greater demand for practical assistance can be expected in the future. The availability of practical services will need to be increased in order to effectively meet cancer patient needs.
Relationship between amino acid dose and gastric secretory response.
Authors: A Gough, V Rai, E Mariano, J H Landor
Journal: Gut (1980)

Gastric secretory dose-response studies, using an 8.5% mixed L-amino acid solution as the agonist, were carried out in three dogs with Heidenhain pouches and gastric fistulae. Secretory responses of the Heidenhain pouches were measured during two hour infusions of amino acids given at rates of 0, 0.05, 0.1, 0.2, 0.4, 0.8, and 1.6 g/kg/h and plasma amino nitrogen was measured before and during the infusion. Three separate studies at each dose level were made in each dog. The maximum secretory response occurred at the dose of 0.4 g/kg/h and amounted to approximately 20% of the maximal histamine response. Larger doses produced no additional increase in secretion or an actual decrease in secretory rate. It is concluded that the solution of amino acids used acts as a modest gastric agonist and that increases in plasma amino nitrogen such as may be observed after a protein meal are capable of eliciting a slight, but definite, gastric secretory response.