tbuckley/cabot-search huggingface dataset:
Pharmacokinetics and pharmacodynamics of fluoroquinolones in the respiratory tract
Authors: R. Wise, D. Honeybourne
Journal: European Respiratory Journal (1999)

Pharmacokinetic and pharmacodynamic features are important predictors of the therapeutic efficacy of an antibiotic. In respiratory tract infection, study of the clinical implication of pharmacodynamic features is complicated as infection occurs at several distinct sites. To ensure microbiological efficacy, antibiotics should not only be active against common respiratory pathogens but should also penetrate to the sites of infection. The newer fluoroquinolones combine good activity against Gram-negative and "atypical" organisms with extended Gram-positive activity, and are unaffected by penicillin susceptibility status and beta-lactamase production. Long terminal half-lives allow once-or twice-daily dosing, and a concentration in lung tissue at levels many times higher than is observed in the serum. Although the benefit of antibiotics in some lower respiratory tract infections has been questioned, they have proved effective in community-acquired pneumonia and acute exacerbations of chronic obstructive pulmonary disease. Early studies of oral fluoroquinolones versus intravenous or oral treatment with one or more agents in community-acquired pneumonia have shown promise. Although resistance is a potential problem with increased fluoroquinolone use, its rapid development is not anticipated. In conclusion, the broad-spectrum antimicrobial activity, tissue distribution and safety profile of fluoroquinolones suggest that they have a place in respiratory tract infection.
Expectant management of patients with unilateral hepatic duct stricture and liver atrophy.
Authors: N S Hadjis, D Carr, I Blenkharn, L Banks, R Gibson, L H Blumgart
Journal: Gut (1986)

Three patients with postcholecystectomy unilateral hepatic duct stricture and subsequent liver atrophy were treated conservatively, with a successful outcome of up to three years follow up. A better understanding of the pathophysiological sequelae of segmental hepatic duct obstruction suggests that in such circumstances reconstructive surgery, with its attendant risks, may not invariably be necessary.
Cigarette Smoke Impaired Antiviral Responses of Airway Epithelial Cells to dsRNA are Associated with Upregulation of Glucocorticoid Induced Leucine Zipper (GILZ)
Authors: R.U. Lee, J. Eddleston, J. Herschbach, B.L. Zuraw
Journal: Journal of Allergy and Clinical Immunology (2009)

RATIONALE: Rhinovirus (RV) URTIs are commonly associated with asthma exacerbations.Recent data suggests RV may be persistent in the airways of children and adults with asthma.METHODS: Children with or without asthma, either with or without URTIs, had exhaled RV aerosols sampled using a novel sampling mask plus nasal mucous collected.Virus was detected by PCR.URTI was established by questionnaire.RESULTS: % 1ve RV was detected in samples as follows Asthma 1ve, URTI 1ve, (n 5 62): mucous 34%, exhaled 37% Asthma 1ve, URTI 2ve, (n 5 54): mucous 2%, exhaled 39% Asthma 2ve, URTI 1ve, (n 5 42): mucous 12%, exhaled 12% Asthma 2ve, URTI 2ve, (n 5 29): mucous 0%, exhaled 0% CONCLUSIONS: Many children with asthma who do not have symptoms of URTIs may have persistent RV infections in their lower airways only, which can be detected in their exhaled breath, but not in nasal mucous.Whether the carriage of these quiescent infections is influenced by anti-inflammatory medications and affects clinical outcomes requires exploration.
Abstract 3876: TRIM16 is a prognostic marker for patients with lymph node metastatic melanoma.
Authors: Belamy B. Cheung, Selina K. Sutton, Owen Tan, Jessica Koach, Bing Liu, Tao Liu, Richard A. Scolyer, Xu Dong Zhang, Glenn M. Marshall
Journal: Cancer Research (2013)

Abstract The family of tripartite-motif (TRIM) proteins is involved in diverse cellular processes, ranging from innate immunity, oncoprotein, and tumor suppressor roles. TRIM16 overexpression confers retinoid sensitivity in retinoid-resistant cancer cells. Previously, we found a strong correlation between loss of TRIM16 expression and disease progression in two human cancers: neuroblastoma and squamous cell carcinoma of skin. Moreover, TRIM16 acted as a tumor suppressor in both cancers through effects on cell cycle and migration. Here we examined the potential role of TRIM16 as a tumor suppressor in melanoma. We found that the endogenous TRIM16 expression level in seven melanoma cell lines was significantly lower than in normal human melanocytes. Overexpression of TRIM16 reduced cell viability and proliferation in multiple melanoma tumor cell lines assessed by the Alamar Blue assay, compared to empty vector controls (P &amp;lt; 0.01). Overexpression of TRIM16 also decreases cell migration and induces apoptosis in melanoma cells. Immunohistochemical analysis demonstrated that TRIM16 expression is decreased in human metastatic melanoma tissue samples (Stage 3 and 4) compared to dysplastic compound nevi and primary melanomas (n=91). Most importantly, we have demonstrated that high TRIM16 expression is a favourable prognostic marker of survival (P=0.025) in a cohort of 170 melanoma patients with lymph node metastases. Median survival was 59 months in the high TRIM16 expression group (n=64), compared to 16 months in the low TRIM16 expression group (n=106). We also show overexpression of TRIM16 in melanoma cells lines induced interferon-beta 1 (IFNB1) mRNA expression, and IFNB1 expression is required for inhibition of cell proliferation by TRIM16. IFNB1 expression was also reduced in human metastatic melanoma tissue samples (n=91), and positively correlated with TRIM16 expression in patient samples. Our in vitro and in vivo data suggest that TRIM16 is a prognostic marker for patients with lymph node metastatic melanoma and may play an important role in melanoma tumor metastasis. Citation Format: Belamy B. Cheung, Selina K. Sutton, Owen Tan, Jessica Koach, Bing Liu, Tao Liu, Richard A. Scolyer, Xu Dong Zhang, Glenn M. Marshall. TRIM16 is a prognostic marker for patients with lymph node metastatic melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3876. doi:10.1158/1538-7445.AM2013-3876
The induction of augmented granulocyte adherence by inflammation. Mediation by a plasma factor.
Authors: A L Lentnek, A D Schreiber, R R MacGregor
Journal: Journal of Clinical Investigation (1976)

The adherence of granylocytes to surfaces, measured in vitro in nylon fiber columns, is inhibited by in vivo administration of anti-inflammatory agents. Therefore, the effect of inflammation itself was assessed in blood from patients with acute inflammatory diseases. Mean adherence in these patients was twice normal (56.4 +/- 5.6% vs. 29.4 +/- 5.2%); their plasma contained a factor that augmented adherence of normal cells to 47.5 +/- 5.6% whereas the patient's cells showed a normal level of adherence (34.0 +/- 6.8%) when resuspended in normal plasma. Although exudate fluid from exprimental inflammation also contained the augmenting factor, cells from the exudate maintained their high level of adherence after washing and suspension in normal plasma. The augmenting factor detected in plasma from patients with inflammation was not present in serum and was inactivated by heating plasma to 56 degrees C for 30 min; restoration of augmenting activity was accomplished by addition of 20% guinea pig serum to the heat-treated plasma. Because the guinea pig serum itself did not increase adherence when added to normal plasma, it appears that the augmenting factor is heat-stable, but requires a heat-labile cofactor like complement. Sephadex G-200 fractionation of inflammatory plasma showed adherence-augmenting activity in the majority of fractions, with peak activity in the fractions corresponding to approximate molecular wts of 30,000, 160,000 and 400,000.
(18) Congenital hypotrichosis—for diagnosis
Authors: M.J. Cheesbrough, P.D.C. Kinmont
Journal: British Journal of Dermatology (1978)

Journal Article (18) Congenital hypotrichosis—for diagnosis Get access M.J. Cheesbrough, M.J. Cheesbrough Children's Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar P.D.C. Kinmont P.D.C. Kinmont Children's Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 99, Issue s16, 1 December 1978, Pages 43–44, https://doi.org/10.1111/j.1365-2133.1978.tb15240.x Published: 01 December 1978
Age specific mortality in Finnish women with chronic inflammatory joint diseases during 1977-93
Authors: A. SAVOLAINEN, H. KAUTIAINEN, H. ISOMAKI, R. MYLLYKANGAS-LUOSUJARVI, K. AHO
Journal: Annals of the Rheumatic Diseases (1997)

It has been known for 40 years ago that rheumatoid arthritis (RA) is associated with reduced life expectancy,1 a finding confirmed by numerous studies.2-4 Most RA mortality studies compare observed deaths in patient cohorts with expected from reference populations or case controls. Because of differences in composition of study series, length of follow up, and means to express the findings, the figures are not fully comparable. Crude death rates, however, have not improved.3 4 In 1953, Cobb et al 1 reported a standardised mortality ratio (SMR) of 1.3; in the recent study by Wolfe et a l5the SMR was 2.3. In this study we have made use of the Finnish nationwide sickness insurance statistics to follow up age specific mortality in women with chronic inflammatory joint diseases during a 17 year period.

Since 1966, the Sickness Insurance Act has provided for the prescription of drugs (glucocorticoids, non-steroidal anti-inflammatory drugs, and disease modifying antirheumatic drugs) free of charge, usually lifelong, for chronic inflammatory joint diseases (since 1987, 90% of the costs have been reimbursed). The scheme covers the entire population, and almost all patients with RA make use of it.6 Eligibility requires …
Is It Sufficient to Quantify Aspiration for Predicting Aspiration Pneumonia?
Authors: Claudio Parrilla, Venanzio Valenza, Lea Calò, Giulio Cesare Passali, Paola Castaldi, Jacopo Galli
Journal: Clinical Nuclear Medicine (2008)

A 63-year-old man previously treated with a subtotal laryngectomy, presented with a 4 month history of severe dysphagia and intractable aspiration. On the last follow-up he underwent a scintigraphic swallowing procedure that showed severe tracheopulmonary aspiration with visualization of the trachea, of the right and left bronchi, and evidence of good airway clearance on the follow-up scan obtained 15 minutes later. A chest radiograph showed no signs of pneumonia. Oropharyngeal-esophageal scintigraphy is still the gold standard technique to objectively assess and quantify tracheopulmonary aspiration, and to check the airway’s clearance mechanism. Pulmonary clearance represents the most important factor to prevent aspiration pneumonia in the case of intractable aspiration. Quantitative parameters are not sufficient to predict aspiration pneumonia.
Hysterectomy, HMOs, and Appropriateness-Reply
Authors: Elizabeth A. McGlynn
Journal: JAMA (1993)

In Reply.  —We do not agree that individual case review is the criterion standard for making appropriateness determinations. In fact, no criterion standard exists and there are significant problems with the reliability of implicit peer review. 1 One advantage of the RAND/UCLA approach is that the appropriateness criteria are explicit; disagreements with the criteria can be discussed and results analyzed to determine the sensitivity of conclusions to controversial elements. While we know that some cases might be overturned on peer review because of extenuating clinical circumstances not covered by the guidelines or individual patient preferences, we also know this occurs among patients receiving care for both appropriate and inappropriate indications.  Because of space limitations we did not mention in our Methods section that all patients whose care was scored as inappropriate were re-reviewed by a physician researcher to ensure that the data on which the ratings are based were accurate.
Percutaneous closure of patent foramen ovale in patients with paradoxical embolism: impact of patent foramen ovale dedicated devices on procedural complications and residual shunt
Authors: Markus Schwerzmann, Bernhard Meier, Andreas Wahl, Franz R. Eberli, Christian Seiler, Haresh Mehta, Marianne Zimmerli, Stephan Windecker
Journal: Journal of the American College of Cardiology (2002)
Functional Gastrointestinal Disorders: A Behavioral Medicine Approach
Authors: Carla H. Ginsburg
Journal: JAMA (1984)

While irritable bowel syndrome (IBS) is, indeed, familiar to most physicians, it is a syndrome for which there seems to be little agreement as to diagnostic criteria. It is the thesis of this book that current explanatory models for functional bowel disorders in general, and IBS in particular, are inadequate to account for all of the complex clinical features involved. With this in mind, the author, a psychiatrist, proposes an alternative behavior model explaining IBS with a behavioral-analysis approach for therapy. In the first half of the book (chapters 1 through 5), the author gives an extensive review of the literature, with tables comparing studies on IBS. These chapters are most informative and provide a good perspective on the field. Before the literature review on colonic physiology, chapter 4 provides an excellent primer on colonic physiology for the nongastroenterologist. The remainder of the book is devoted to expanding the author's
261. In Vivo Over-Expression of Fractalkine, a Putative Neuron-to-Glia Signal, To Characterize Underlying Mechanisms of Neuropathic Pain
Authors: Stephen J. Langer, David Busha, Erin D. Milligan, Travis S. Hughes, Julie Wieseler-Frank, Linda R. Watkins, Leslie A. Leinwand
Journal: Molecular Therapy (2006)

We have previously shown that fractalkine (FKN), the newest member of the chemokine family, plays an integral role in the initiation and maintenance of exaggerated pain states. Fractalkine is expressed on the external surface of sensory nerves and some dorsal spinal cord neurons. The receptor for FKN is found predominately on spinal cord microglia. Strong neuronal excitation induces the cleavage of the FKN chemokine domain forming a soluble signal that can act on nearby glia. Spinal cord microglia are important in diverse forms of enhanced pain states via the release of the pro-inflammatory cytokines, interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF). We have shown that the pain-enhancing effects of spinally administered (via intrathecal injection) FKN are mediated, at least in part, via release of the glial proinflammatory cytokine, IL-1.Thus FKN may be a neuron-to-glia signal that triggers glial activation and consequent pain facilitation. To further elucidate the underlying mechanisms of FKN's role in neuropathic pain, we have engineered plasmid expression vectors encoding soluble forms of the active chemokine domain, CX3CL1. Concurrent studies are designed to determine whether two sequential intrathecal injections, each 100 μg in 20 μL of C X3CL1 plasmid leads to chronic neuropathic pain as measured by hypersensitivity to light mechanical stimuli presented to the hind paws of rats. Exaggerated pain will be reassessed every four days to determine the duration of FKN- induced hypersensitivity. Further we will determine levels of FKN expression in cerebrospinal fluid and spinal cord microglial activation. Additional studies will examine the pro-inflammatory cytokine profile (IL-1, IL-6, and TNF) in cerebrospinal fluid after chronic FKN over-expression in behaviorally verified rats. This system should allow for the examination of newly developed FKN antagonists to treat neuropathic pain.
Microdialysis of Glucose in Subcutaneous Adipose Tissue up to 3 Weeks in Healthy Volunteers
Authors: Klaas J Wientjes, Pieter Vonk, Yvonne Vonk-van Klei, Adelbert JM Schoonen, Nico W Kossen
Journal: Diabetes Care (1998)

To measure possible changes in dialysate glucose concentrations over time, to validate the diffusional model for glucose transport from tissue to the probe, and to evaluate the actual glucose concentration in adipose tissue.Glucose concentrations in the subcutaneous adipose tissue of five healthy subjects (age 25 +/- 2.7 years, BMI 23.2 +/- 2.3 kg/m2 [mean +/- SD]) were measured by the microdialysis technique and compared with blood glucose. We applied microdialysis probes with hollow fibers of various membrane length (10-35 mm), used eight perfusion flow rates (0.5-20 microl/min), and perfused four glucose solutions (0.0, 2.8, 8.3, 11.1 mmol/l).After implantation, a substantial decrease in glucose recovery to the lowest value of 26 +/- 10% of the final plateau value was noted during the first few hours (n = 4). Recovery increased and stabilized after 5-9 days at 84.0 +/- 7.4% of capillary blood glucose when a flow rate of 0.5 microl/min was applied. According to the zero net-flux method, the glucose concentration in equilibrium, Cequi, with the surrounding tissue can be obtained. This concentration also decreases; however, 1 h after recovery, Cequi increases again over 1 or 2 days to a stable value that is not significantly different from the measured capillary blood glucose (P < 0.05). Using various perfusion flow rates and probes (membrane length 10-35 mm), it is shown that diffusion is the rate-limiting process for glucose transport through tissue.Insertion of the microdialysis probes causes damage to the adipose cells and the vascular bed around the probe. Glucose recovery decreases because of a lower blood supply. In 5-9 days, glucose recovery increases; apparently, this time is needed to repair the microstructure of tissue around the probe. After stabilization of the recovery, no loss of probe permeability, which is due to biocompatibility problems, was seen. The change during the 2 days in equilibrium concentration is probably caused by an inflammation reaction that consumes glucose around the probe. The individual increase in recovery during the 1st days after probe insertion until a stable plateau value is reached (flow rate >0 microl/min) is complicated for short-term clinical glucose measurements in adipose tissue. After stabilization, the mean equilibrium concentration of all subjects was equal to the mean capillary blood glucose concentration. Therefore, we conclude that capillary blood glucose concentration probably is the driving force for diffusion through the capillary wall into the probe and is not some interstitial concentration.
Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma
Authors: Cécile Guichard, Giuliana Amaddeo, Sandrine Imbeaud, Yannick Ladeiro, Laura Pelletier, Ichrafe Ben Maad, Julien Calderaro, Paulette Bioulac-Sage, Mélanie Letexier, Françoise Degos, Bruno Clément, Charles Balabaud, Eric Chevet, Alexis Laurent, Gabrielle Couchy, Eric Letouzé, Fabien Calvo, Jessica Zucman-Rossi
Journal: Nature Genetics (2012)
River Blindness: A Success Story under Threat?
Authors: María-Gloria Basáñez, Sébastien D. S Pion, Thomas S Churcher, Lutz P Breitling, Mark P Little, Michel Boussinesq
Journal: PLoS Medicine (2006)

“The accomplishments of this Programme inspire all of us in public health to dream big dreams. It shows we can reach ‘impossible’ goals and lighten the burden of millions of the world's poorest people ….” These were the concluding words by former World Health Organization Director-General Gro Harlem Brundtland at the closure ceremony of the Onchocerciasis Control Programme in West Africa (OCP) in December 2002 [1]. The success of the OCP is so undeniable and exemplary, with 600,000 cases of blindness prevented, 18 million children born in areas freed from the risk of blindness, and 25 million hectares of land safe for resettlement, that river blindness is currently considered a disease of the past. This perception nonetheless forgets that OCP covered, at most, 1,200,000 square kilometers to protect 30 million people in 11 countries, leaving a remaining 100 million people in areas where active transmission of onchocerciasis still occurs. After its 28-year fight OCP may have won a battle, but a much more difficult task lies ahead before we can claim victory against river blindness [2].
Pulmonary Infiltration with Eosinophilia
Authors: Daniel Jackson, Ellard Yow
Journal: New England Journal of Medicine (1961)

FARMER'S lung resembles Loeffler's syndrome, for, at times, it manifests the triad of pulmonary infiltrations, eosinophilia and a benign clinical course. To relegate it to the long, uncritical list of causes of Loeffler's syndrome lends a mysterious air to the disease.1 Each new article mentions it until it is carried along because of repetition rather than because of an exacting analysis of its true position. With this in mind, we present 2 clinical cases of farmer's lung, review this new disease and examine its pathogenesis and treatment.Two patients with pulmonary infiltration and eosinophilia were studied in Houston. Both had . . .
Tuberous Sclerosis
Authors: David Marshall, George B. Saul, Ernest Sachs
Journal: New England Journal of Medicine (1959)

BOURNEVILLE,1 in 1880, was the first to recognize tuberous sclerosis as a pathological entity. He was chiefly concerned with the finding of multiple areas of sclerosis in the brains of young adults who, during their relatively short lives, had suffered from epilepsy and mental deficiency. Significantly, he pointed out the frequent coexistence of pr-mitivecell tumors of the kidneys as well as adenoma sebaceum of the face. However, he considered these findings coincidental. It was not until 1908 that Vogt2 clearly defined the clinical syndrome of mental deficiency, epilepsy and adenoma sebaceum. Shortly thereafter Sherlock chose to label this entity "epiloia" . . .
Should we use large scale healthcare interventions without clear evidence that benefits outweigh costs and harms? Yes
Authors: Bernard Crump
Journal: BMJ (2008)

Obtaining definitive evidence on the effects of large scale interventions can be difficult. <b>Bernard Crump </b>believes that implementation with careful monitoring is justified but <b>Seth Landefeld and colleagues (</b>doi: 10.1136/bmj.a144) argue that acting without proof of net benefit is both costly and potentially damaging to health
Chemical induction of nondisjunction in drosophila.
Authors: C Ramel, J Magnusson
Journal: Environmental Health Perspectives (1979)

Tests for chemically induced nondisjunction and loss of the sex chromosomes in Drosophila were performed. Of 31 compounds tested four gave rise only to an increase of XO exceptions, indicating the induction of chromosome loss. Six compounds, all known spindle inhibitors (colchicine, organic mercury, lead, and tin compounds) gave rise to an increase both of XXY and XO or of only XXY. The effect by metalloorganic compounds of which methylmercury was studied particularly closely, follows a peculiar pattern. In females with structurally normal X chromosomes only an increase of XX gametes is obtained, while with X chromosomes heterozygous for long inversions only O gametes are increased. The data indicates that the effect of the metal compounds occurs at first meiosis and that the process is connected with a meiotic drive, giving rise to a preferential segregation of the two X chromosomes to the functioning pole. The increase only of O gametes with structurally heterozygous X chromosomes can tentatively be explained by a loss due to crossing over within the inversion. An increase of the effect of methyl mercury was obtained where the normal pairing of the X chromosomes was interfered with by means of autosomal inversions. Likewise a synergistic increase of nondisjunction was obtained when a temperature chock of 10 degrees C was applied together with treatment with methylmercury. It is concluded that chemical induction of nondisjunction can be studied in Drosophila, but the sensitivity of the test is rather low and large amount of material is required.