tbuckley/cabot-search huggingface dataset:
Liposomal formulations for enhanced lymphatic drug delivery
Authors: Hyeongmin Kim, Yeongseok Kim, Jaehwi Lee
Journal: Asian Journal of Pharmaceutical Sciences (2013)

The lymphatic system that extends throughout the whole body is one of useful targets for efficient drug delivery. The intestinal lymphatic drug delivery has been actively studied to date because administered drugs can avoid the first-pass metabolism in the liver, resulting in improvement of oral bioavailability. Drugs must be hydrophobic in order to be transported into the intestinal lymphatics because the lipid absorption mechanism in the intestine is involved in the lymphatic delivery. Therefore, various lipid-based drug carrier systems have been recently utilized to increase the transport of drug into the intestinal lymphatics. Lipidic molecules of the lipid-based drug delivery systems stimulate production of chylomicrons in the enterocytes, resulting in an increase in drug transport into lymphatic in the enterocytes. This review summarizes recently reported information on development of liposomal carriers for the intestinal lymphatic delivery and covers important determinants for successful lymphatic delivery.
Epidemiology of Ventilator-acquired Pneumonia Based on Protected Bronchoscopic Sampling
Authors: DAVID L. GEORGE, PAMELA S. FALK, RICHARD G. WUNDERINK, KENNETH V. LEEPER, G. UMBERTO MEDURI, ELAINE L. STEERE, CATHY E. CORBETT, C. GLEN MAYHALL
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

We performed a prospective observational cohort study of the epidemiology and etiology of nosocomial pneumonia in 358 medical ICU patients in two university-affiliated hospitals. Protected bronchoscopic techniques (protected specimen brush and bronchoalveolar lavage) were used for diagnosis to minimize misclassification. Risk factors for ventilator-associated pneumonia were identified using multiple logistic regression analysis. Twenty-eight cases of pneumonia occurred in 358 patients for a cumulative incidence of 7.8% and incidence rates of 12.5 cases per 1, 000 patient days and 20.5 cases per 1,000 ventilator days. Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Hemophilus species made up 65% of isolates from the lower respiratory tract, whereas only 12.5% of isolates were enteric gram-negative bacilli. Daily surveillance cultures of the nares, oropharynx, trachea, and stomach demonstrated that tracheal colonization preceded ventilator-associated pneumonia in 93.5%, whereas gastric colonization preceded tracheal colonization for only four of 31 (13%) eventual pathogens. By multiple logistic regression, independent risk factors for ventilator- associated pneumonia were admission serum albumin <= 2.2 g/dl (odds ratio [OR] 5.9; 95% confidence interval [CI] 2.0-17.6; p = 0.0013), maximum positive end-expiratory pressure >= 7.5 cm H2O (OR, 4.6; 95% CI, 1.4 to 15.1; p = 0.012), absence of antibiotic therapy (OR, 6.7; 95% CI, 1.8 to 25.3; p = 0.0054), colonization of the upper respiratory tract by respiratory gram-negative bacilli (OR, 3.4; 95% CI, 1.1 to 10.1; p = 0.028), pack-years of smoking (OR, 2.3 for 50 pack-years; 95% CI, 1. 2 to 4.2; p = 0.012), and duration of mechanical ventilation (OR, 3. 4 for 14 d; 95% CI, 1.5 to 7.8; p = 0.0044). Several of these risk factors for ventilator-associated pneumonia appear amenable to intervention.
THE PATHOGENESIS OF HEMOPHILIA
Authors: John B. Graham, Emily M. Barrow
Journal: The Journal of Experimental Medicine (1957)

It has been possible to duplicate in the hemophilic dog four of the major experiments which have suggested in humans an "anticephalin" hypothesis for the pathogenesis of hemophilia. The experiments in the dog have been considerably extended, as compared with the human experiments, by a variety of techniques. I. Asbestos was placed in contact with hemophilic dog plasma, and the clotting time became shorter. When transfused, this plasma had no effect on the defective prothrombin utilization of hemophilic dogs, in contrast to untreated normal plasma. II. The ionic strength of native dog plasma and dog plasma citrated (38 per cent sodium citrate) then recalcified (0.2 M CaCl(2)) were calculated. The ionic strength of the native plasma was approximately 0.15 while that of the citrated plasma was approximately 0.21. Conductivity and freezing point determinations on the plasmas described above were consistent with the idea that the ionic strength of the citrated plasma was significantly higher. The biphasic dilution curve, to which much significance has been attached in arriving at the "anticephalin" hypothesis, can be produced readily in the dog. Diluting dog plasma with "iso-ionic" or "hyper-ionic" NaCl solution abolished the biphasic phenomenon. Dilution with distilled water exaggerated the biphasic curve. These experiments suggest that the biphasic curve is an artifact of uncontrolled ionic strength. III. The prothrombin utilization rates of undiluted whole hemophilic dog blood and hemophilic dog blood diluted 1:2 with 0.85 per cent NaCl were found to be the same. IV. Ether extraction of both normal and hemophilic dog plasma removed fibrinogen and reduced somewhat the concentration of prothrombin. In treated normal plasma AHF was reduced to the level of untreated hemophilic plasma, thus producing a quasi-hemophilic plasma. Defibrination and ether extraction of both normal and hemophilic dog plasma "generated" clotting activity which shortened the clotting time of hemophilic plasma and was active in the thromboplastin generation test. The activity "generated" by defibrination and ether extraction of dog plasma was adsorbed by a BaSO(4) suspension and shown, therefore, not to be the anti-hemophilic factor (AHF). Transfusion of ether-extracted normal or hemophilic dog plasma into hemophilic dogs had no effect on the prothrombin utilization rate, unlike untreated normal plasma which had a marked effect. Thus, four of the main lines of evidence supporting the "anticephalin" hypothesis were duplicated in the dog. However, by extending the experiments it was found that all were explainable on bases other than the presence of "anticephalin." Such an hypothesis is not necessary, therefore, to explain the pathogenesis of canine hemophilia. The apparent identity of hemophilia in the two species suggests that the hypothesis is also not applicable to humans.
Effective anti-tuberculosis therapy correlates with plasma small RNA
Authors: Isobella Honeyborne, Marc C Lipman, Clare Eckold, Dimitrios Evangelopoulos, Stephen H Gillespie, Alexander Pym, Timothy D McHugh
Journal: European Respiratory Journal (2015)

Small RNA (smRNA) is a diverse family of translation regulation molecules, which includes microRNA (miRNA). Changes in miRNA have been reported in association with respiratory disease [1] and in mycobacterial infection [2]. Studies have measured concentrations of miRNA pooled from multiple subjects with active tuberculosis (TB) disease compared with latently infected individuals and healthy controls [3]. However, this approach cannot assess variation between individuals, nor does it describe changes that might occur with treatment, both of which may be helpful in characterising and predicting patient outcome. Plasma small RNA concentration declines in response to anti-tuberculosis therapy and is independent of HIV-status <http://ow.ly/IxOaD> We would like to thank S. Bokhari and S. Christou (Centre for Clinical Microbiology, Dept of Infection, University College London, London, UK) for assistance with sample processing and C. Smith (Research Dept of Infection and Population Health, University College London, London, UK) for statistical support.
Visual and different automatic scoring profiles of respiratory variables in the diagnosis of sleep apnoea-hypopnoea syndrome
Authors: O Carrasco, JM Montserrat, P Lloberes, C Ascasco, E Ballester, C Fornas, R Rodriguez-Roisin
Journal: European Respiratory Journal (1996)

The purpose of our study was to explore the diagnostic accuracy of different methods of scoring night time recording of respiratory variables (NTRRV) for the diagnosis of the sleep apnoea-hypopnoea syndrome (SAHS). Within a 2 week period, we performed a partially attended night time recording of respiratory variables and a full polysomnography (PSG) for reference in patients with suspected SAHS. Night time recording of respiratory variables was carried out using equipment which records, and continuously displays on a monitor, oximetry, airflow, chest and abdominal motion and body position. Night time recording of respiratory variables was scored manually and automatically, according to different combinations of the parameters described previously. Full polysomnography was performed in the Sleep Laboratory following conventional standards. Thirty six patients were studied. Visual analysis and different automatic scoring profiles of night time recording of respiratory variables were compared to full polysomnography in terms of agreement, sensitivity and specificity. Visual scoring of night time recording of respiratory variables gave the finest agreement-sensitivity-specificity relationship. Automatic scoring of nighttime recording of respiratory variables showed a trend to underestimate the apnoea-hypopnoea index (AHI) with respect to full polysomnography due mainly to underrecognition of hypopnoeas. Agreement-sensitivity-specificity relationships of automatic night time recording of respiratory variables with respect to full polysomnography varied depending on the automatic profile used. Some had a good agreement and sensitivity whilst others had a good specificity. These findings show that visual scoring of night time recording of respiratory variables is the most accurate method of analysis when compared to full polysomnography. The usefulness of the automatic methods of scoring of respiratory variables depends on the end-point chosen and is not reliable enough to be used in all situations. Night time recording of respiratory variables represents a real complement to conventional full polysomnography in clinical practice.
Azathioprine hypersensitivity in a patient with peripheral demyelinating polyneuropathy
Authors: R. Hinrichs, L.A. Schneider, C. Özdemir, G. Staib, K. Scharffetter- Kochanek
Journal: British Journal of Dermatology (2003)

Sir, For decades, azathioprine has been widely prescribed for immunosuppression in autoimmune diseases and organ transplantation.1 Azathioprine hypersensitivity is a rare but severe complication characterized by nausea, diarrhoea, dizziness, rigor, renal dysfunction and haemolytic anaemia.2–4 Liver toxicity, leucocytosis, increased C‐reactive protein, fever and hypotension have also been reported.5, 6 Cutaneous symptoms of azathioprine hypersensitivity include a macular or maculopapular erythema, vesicles or pustules, urticaria, vasculitis, erythema multiforme, erythema nodosum, petechiae and purpura.2, We describe a 71‐year‐old white woman with a history of chronic inflammatory demyelinating peripheral polyneuropathy. During hospitalization in July 2001 for treatment of the polyneuropathy she received azathioprine, amoxicillin plus clavulanic acid, omeprazole and heparin. Several days after the medication was started she developed oedema of the face, chest and arms. All medications were withdrawn and were not administered again. As her neuropathy deteriorated in January 2002, the question was addressed whether she could be treated with azathioprine again.
Bevacizumab treatment of symptomatic pseudoprogression after boron neutron capture therapy for recurrent malignant gliomas. Report of 2 cases
Authors: Shin-Ichi Miyatake, Motomasa Furuse, Shinji Kawabata, Takashi Maruyama, Toshihiro Kumabe, Toshihiko Kuroiwa, Koji Ono
Journal: Neuro-Oncology (2013)

Bevacizumab, an anti–vascular endothelial growth factor antibody, has been used for the treatment of radiation necrosis. Thus far, however, there has been no definitive report on its use for the treatment of symptomatic pseudoprogression. Here we report 2 cases of successful treatment with bevacizumab for symptomatic pseudoprogression after boron neutron capture therapy (BNCT) was applied for recurrent malignant gliomas. Two recurrent malignant gliomas received BNCT. Both cases were treated with intravenous administration of bevacizumab at the deterioration that seemed to be symptomatic pseudoprogression. The first case was recurrent glioblastoma multiforme and the second was recurrent anaplastic oligoastrocytoma. Both cases recurred after standard chemoradiotherapy and were referred to our institute for BNCT, which is tumor-selective particle radiation. Just prior to neutron irradiation, PET with an amino acid tracer was applied in each case to confirm tumor recurrence. Both cases showed deterioration in symptoms, as well as on MRI, at intervals of 4 months and 2 months, respectively, after BNCT. For the first case, a second PET was applied in order to confirm no increase in tracer uptake. We diagnosed both cases as symptomatic pseudoprogression and started the intravenous administration of 5 mg/kg bevacizumab biweekly with 6 cycles. Both cases responded well to this, showing rapid and dramatic improvement in neuroimaging and clinical symptoms. No tumor progression was observed 8 months after BNCT. Bevacizumab showed marked effects on symptomatic pseudoprogression after BNCT. BNCT combined with bevacizumab may prolong the survival of patients with recurrent malignant gliomas.
Shoulder pain in elite swimmers: primarily due to swim-volume-induced supraspinatus tendinopathy
Authors: Mya Lay Sein, Judie Walton, James Linklater, Richard Appleyard, Brent Kirkbride, Donald Kuah, George A C Murrell
Journal: British Journal of Sports Medicine (2008)

Background/hypothesis Shoulder pain in elite swimmers is common, and its pathogenesis is uncertain. Hypothesis/study design The authors used a crosssectional study design to test Jobe’s hypothesis that repetitive forceful swimming leads to shoulder laxity, which in turn leads to impingement pain. Methods Eighty young elite swimmers (13–25 years of age) completed questionnaires on their swimming training, pain and shoulder function. They were given a standardised clinical shoulder examination, and tested for glenohumeral joint laxity using a non-invasive electronic laxometer. 52/80 swimmers also attended for shoulder MRI. Results 73/80 (91%) swimmers reported shoulder pain. Most (84%) had a positive impingement sign, and 69% of those examined with MRI had supraspinatus tendinopathy. The impingement sign and MRIdetermined supraspinatus tendinopathy correlated strongly (r s =0.49, p&lt;0.00001). Increased tendon thickness correlated with supraspinatus tendinopathy (r s =0.37, p&lt;0.01). Laxity correlated weakly with impingement pain (r s =0.23, p&lt;0.05) and was not associated with supraspinatus tendinopathy (r s =0.14, p=0.32). The number of hours swum/week (r s =0.39, p&lt;0.005) and weekly mileage (r s =0.34, p=0.01) both correlated significantly with supraspinatus tendinopathy. Swimming stroke preference did not. Conclusions These data indicate: (1) supraspinatus tendinopathy is the major cause of shoulder pain in elite swimmers; (2) this tendinopathy is induced by large amounts of swimming training; and (3) shoulder laxity per se has only a minimal association with shoulder impingement in elite swimmers. These findings are consistent with animal and tissue culture findings which support an alternate hypothesis: the intensity and duration of load to tendon fibres and cells cause tendinopathy, impingement and shoulder pain.
Radiofrequency ablation of supraventricular tachycardia using an ultrasound-based navigational system and a cooled ablation catheter
Authors: David M. Fitzgerald, Thomas Wannenburg, Tony W. Simmons, Pihua Fang, Nancy L. Radtke, Craig Hedrick, Karthik Ramaswamy, Wesley K. Haisty
Journal: Journal of the American College of Cardiology (2002)
RESISTANCE TO SPONTANEOUS MOUSE CANCER INDUCED BY INJECTIONS OF OLEIC ACID
Authors: Waro Nakahara
Journal: The Journal of Experimental Medicine (1925)

The experiments reported here show that the resistance of mice to spontaneous neoplastic diseases can be increased by means of oleic acid injections. This is demonstrated (1) by the greatly reduced incidence of local recurrences at the site of operation, and the lessened incidence (2) of primary tumors developing at other locations, (3) of metastases as encountered at autopsy, and (4) of takes of autoplastic tumor grafts, while finally, (5) there is an appreciable increase of the average postoperative longevity. Supplementary to the above results is the finding that in the treated mice the reaction about the implanted cancer graft differs from that encountered in untreated animals.
Temporal arteritis: a form of systemic panarteritis.
Authors: A Sendino, F J Barbado, I Gonzalez-Anglada, E Anton, F Lopez-Barea, J J Vazquez
Journal: Annals of the Rheumatic Diseases (1992)

The case is reported of a patient with giant cell arteritis affecting several organs. The triggering cause of death was a brainstem infarction due to basilar artery thrombosis. The necropsy showed the systemic character of the disease affecting the coronary, bronchial, and ovarian arteries.
Hematopoietic Stem and Progenitor Cells: Clinical and Preclinical Regeneration of the Hematolymphoid System
Authors: Judith A. Shizuru, Robert S. Negrin, Irving L. Weissman
Journal: Annual Review of Medicine (2002)

A vast literature exists on the biology of blood formation and regeneration under experimental and clinical conditions. The field of hematopoiesis was recently advanced by the capacity to purify to homogeneity primitive hematopoietic stem and progenitor cells. Isolation of cells at defined maturational stages has enhanced the understanding of the fundamental nature of stem cells, including how cell fate decisions are made, and this understanding is relevant to the development of other normal as well as malignant tissues. This review updates the basic biology of hematopoietic stem cells (HSC) and progenitors, the evolving use of purified HSC as grafts for clinical hematopoietic cell transplantation (HCT) including immune tolerance induction, and the application of HSC biology to other stem cell fields.
Altered Expression of Neurotensin Receptors Is Associated with the Differentiation State of Prostate Cancer
Authors: Stephanie L. Swift, Julie E. Burns, Norman J. Maitland
Journal: Cancer Research (2010)

Abstract In prostate cancer, traditional treatments such as androgen response manipulation often provide only temporary resolution of disease, with emergence of a more aggressive, androgen-independent tumor following initial therapy. To treat recurrent disease, cell surface proteins that are specifically overexpressed on malignant cells may be useful for generating targeted therapeutics. Recent evidence suggests that neurotensin receptors (NTR) are recruited in advanced prostate cancer as an alternative growth pathway in the absence of androgens. In this study, we assessed the potential use of these receptors as targets by analyzing NTR expression patterns in human prostate cell lines and primary prostate tumor cell cultures derived from patient samples. In primary tumor cell cultures, NTR1 was upregulated in cells with a basal phenotype (cytokeratin 1/5/10/14+), whereas NTR2 and NTR3 were upregulated in cells with luminal phenotype (cytokeratin 18+). Similar patterns of NTR expression occurred in benign prostate tissue sections, implicating differentiation state as a basis for the differences observed in tumor cell lines. Our findings support the use of NTRs as tools for therapeutic targeting in prostate cancers composed of both poorly differentiated and/or well-differentiated cells. Cancer Res; 70(1); 347–56
Stratum corneum hydration and amino acid content in xerotic skin
Authors: I. HORII, Y. NAKAYAMA, M. OBATA, H. TAGAMI
Journal: British Journal of Dermatology (1989)

The relationship between clinical severity, the hydration state of the skin surface as assessed by a conductance with a 3.5 MHz high frequency impedance meter, and the amino acid content of the stratum corneum (SC) of six patients with ichthyosis vulgaris and 30 elderly persons with varying degrees of xerosis was investigated. With an increase in the severity of xerosis the SC showed a decrease in hydration and in its extractable amino acid content. There was a significant correlation between the hydration state and amino acid content of the SC. Although there was a significant correlation between the amino acid content of the lower leg SC and that of the forearm SC in the same subject, the former was generally lower, corresponding to the greater incidence of xerosis on the lower leg. These results suggest that a decreased amount of amino acids may be the result of low profilaggrin biosynthesis in the epidermis and that this is involved in the pathogenesis of these xerotic skin conditions. Clinical improvement of the xerosis following treatment with a urea‐containing cream was not accompanied by any significant change in the amino acid content of the SC.
Symbols within words: Have we neglected the AdeNOsine A receptor?
Authors: J KARLINER
Journal: Cardiovascular Research (2005)

See article by Xu et al.  [10]  (pages 803–812) in this issue .

Although considerable experimental effort has been expended during the past two decades in identifying mechanisms of cardioprotection, little of this work has been of direct benefit to patients. Thus, Bolli et al. have expressed concern that the field of myocardial protection is at a crossroads and have emphasized that there is an urgent need for the extensive experimental work in this area to be translated into clinically effective therapy [1]. The authors of this article, who represented a Working Group convened by the National Heart, Lung and Blood Institute, concluded that a Phase III clinical trial of adenosine be undertaken in patients with acute myocardial infarction [1]. This recommendation was based on preclinical studies and on Phase I and II clinical trials of adenosine and related compounds, which showed promise, but which only studied surrogate markers or were insufficiently powered to demonstrate definitive clinical benefit [2–4]. Thus, accumulating a greater understanding of the mechanisms of action of adenosine and its cognate receptor subtypes is both relevant and timely.

It is well-recognized that adenosine has multiple effects on the cardiovascular system. Among its many actions, adenosine enhances coronary blood flow, inhibits adenylyl cyclase activation, and has … 

joel.karliner{at}med.va.gov
Roles for Vitamin K Beyond Coagulation
Authors: Sarah L. Booth
Journal: Annual Review of Nutrition (2009)

Recent interest in vitamin K has been motivated by evidence of physiological roles beyond that of coagulation. Vitamin K and vitamin K-dependent (VKD) proteins may be involved in regulation of calcification, energy metabolism, and inflammation. However, the evidence for many of these proposed roles in the maintenance of health is equivocal. There is also an emerging viewpoint that the biochemical function of vitamin K may extend beyond that of a cofactor for the VKD carboxylation of glutamyl residues (Glus) to carboxylated Glus in VKD proteins.
Public calls for more direct government action to fight health issues
Authors: A. O'Dowd
Journal: BMJ (2010)

The public wants more decisive action from the government on public health, says a survey.

In contrast to the coalition government’s preference for less interference, a survey of almost 1500 adults across Britain has showed that the UK public are in favour of the nanny state.

A survey carried out by YouGov for the Faculty of Public Health, a body representing public health specialists, showed the public would like to see the government ban smoking in cars if there are children in them, make two hours a week of sport compulsory in schools, and introduce …