tbuckley/cabot-search huggingface dataset:
Abstract 611: Alpha-santalol, a chemopreventive agent induces apoptosis in human prostate cancer cells by causing caspase-3 activation
Authors: Ajay Bommareddy, Brittny Rule, Adam L. VanWert, Sreevidya Santha, Chandradhar Dwivedi
Journal: Cancer Research (2012)

Abstract The anticancer effects of α-santalol, a major component of sandalwood oil, have been reported against the development of certain cancers such as skin cancer both in vitro and in vivo. The primary objectives of the current study were to investigate the cancer preventive properties of α-santalol on human prostate cancer cells PC-3 (androgen independent and P-53 null) and LNCaP (androgen positive and P-53 wild-type), and determine the possible mechanisms of its action. The effect of α-santalol on cell viability was determined by trypan blue dye exclusion assay. Apoptosis induction was confirmed by analysis of cytoplasmic histone-associated DNA fragmentation using both an apoptotic ELISA kit and a DAPI fluorescence assay. Caspase-3 activity was determined using caspase-3 (active) ELISA kit. PARP cleavage was analyzed using Immunoblotting. α-santalol at 25-75 µM decreased cell viability in both cell lines in a concentration and time dependent manner. Treatment of prostate cancer cells with α-santalol resulted in induction of apoptosis as evidenced by DNA fragmentation and nuclear staining of apoptotic cells by DAPI. α-santalol treatment also resulted in activation of caspase-3 activity and PARP cleavage. The α-santalol-induced apoptotic cell death and activation of caspase-3 was significantly attenuated in the presence of pharmacological inhibitors of caspas-8 and caspase-9. In conclusion, the present study reveals the apoptotic effect of α-santalol in inhibiting the growth of human prostate cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 611. doi:1538-7445.AM2012-611
Devaluing clinical skills
Authors: P. Wilmshurst
Journal: BMJ (2000)

Poor clinical performance may be the medical issue of greatest concern to the general public and the press, but most doctors realise that clinical performance and welfare of patients often come second to the interests of institutions and loyalty to colleagues.

> Our major medical institutions have placed their financial interests before the welfare of patients 

The public might reasonably expect that a clinician will possess good or at least adequate clinical skills. Yet within our system those attributes are valued least. Distinction awards have traditionally gone to those who have reduced their clinical responsibilities to find time for speaking at conferences, committee work, and medical politics. Increasingly, universities appoint to posts that are nominally for academic clinicians, doctors who moved soon after qualifying into basic science, commonly molecular biology. The main requirements of the universities when appointing a professor in a clinical specialty are not clinical skills, a record of clinical research, or …
The Value of Glossopexy in Pierre-Robin Syndrome
Authors: Chris T. Oeconomopoulos
Journal: New England Journal of Medicine (1960)

THE Pierre-Robin syndrome is a congenital anomaly manifested by glossoptosis, hypoplasia of the mandible, cleft palate, inspiratory retractions of the sternum, cyanosis and malnutrition.1 , 2 It is of particular importance because it is uncommon and in moderate and severe cases leads to respiratory obstruction and death. In the syndrome the infant usually holds his head hyperextended and has stertorous, rasping, labored respirations with sternal retractions (Fig. 1). The poorly fixed tongue tends to be displaced posteriorly, thus obstructing the passage of air when the mouth is closed and causing pressure on the epiglottis that results in closure of the glottis. Therefore, . . .
Physical and infectious titers of helper-dependent adenoviral vectors: a method of direct comparison to the adenovirus reference material
Authors: Donna J. Palmer, Philip Ng
Journal: Molecular Therapy (2004)

Accurate measurements of the physical and infectious titers of adenoviral vectors are crucial for evaluating preclinical studies and for the safety and efficacy of clinical studies. Unfortunately, there are no standardized methods of measurement, consequently variable and unreliable values are the result. Furthermore, infectious titers of helper-dependent adenoviral vectors (HDAd) are difficult to measure because traditional cytopathic effect assays cannot be employed, thus hindering their potential clinical application. In response to this problem, a fully characterized Adenovirus Reference Material (ARM) has been developed to be used as a reference standard for clinical grade adenoviral vectors. However, no specific protocols for this purpose have been provided. To fulfill this important need, we have developed a simple assay involving co-infection of 293 cells with the adenoviral vector and the ARM to permit direct comparisons of their physical and infectious titers. We demonstrate, using a HDAd, that this co-infection assay is reliable, sensitive, and reproducible. Importantly, this assay is inherently unaffected by variables that plague other methods of determining vector titers. This assay is applicable to all human serotype 5 adenoviral vectors and will permit reliable comparisons within and between studies as well as meet an important prerequisite for clinical studies.
Enteric infections, diarrhea, and their impact on function and development
Authors: William A. Petri, Mark Miller, Henry J. Binder, Myron M. Levine, Rebecca Dillingham, Richard L. Guerrant
Journal: Journal of Clinical Investigation (2008)

Enteric infections, with or without overt diarrhea, have profound effects on intestinal absorption, nutrition, and childhood development as well as on global mortality. Oral rehydration therapy has reduced the number of deaths from dehydration caused by infection with an enteric pathogen, but it has not changed the morbidity caused by such infections. This Review focuses on the interactions between enteric pathogens and human genetic determinants that alter intestinal function and inflammation and profoundly impair human health and development. We also discuss specific implications for novel approaches to interventions that are now opened by our rapidly growing molecular understanding.
Intraductal Polypoid Lipid-Rich Neuroendocrine Tumor of the Pancreas with Entrapped Ductules: Case Report and Review of the Literature
Authors: Jaclyn Frances Hechtman, Bernardo Franssen, Daniel M. Labow, Ronald E. Gordon, Christopher J. DiMaio, Eric J. Wilck, Gonzalo Carrasco-Avino, Hongfa Zhu
Journal: Endocrine Pathology (2013)
Penicillin Man: Alexander Fleming and the Antibiotic Revolution
Authors: Sabina Dosani
Journal: BMJ (2004)

Previous studies have shown that the cytochrome P-450-containing hepatic mixed function oxidase system is inhibited <i>in vitro</i> by carbon monoxide (CO). This study reports that acute exposure to CO resulted in inhibition of <i>in vivo</i> drug metabolism in rats as measured by prolonged response to two drugs, hexobarbital and zoxazolamine. Exposure to CO for 90 minutes followed by drug testing in room air resulted in a significantprolongation of response to hexobarbital at a CO concentration of 1000 ppm and a significant prolongation of response to zoxazolamine at a CO concentration of 250 ppm. Exposure to the same CO levels for 90 minutes followed by drug testing in the CO environment resulted in significant enhancement of the CO-induced effect. The prolongation of the pharmacologic responses could be explained by a CO-induced inhibition of the hepatic mixed function oxidase enzyme system responsible for the metabolism of these compounds. Inhalation of atmospheres containing lowered O<sub>2</sub> concentrations also inhibited zoxazolamine metabolism. The data do not, as yet, allow a final conclusion to be made concerning the mechanism of the CO-induced effect, <i>i.e.</i>, whether it is due to the direct effect of CO on P-450 or, alternatively, to an indirect effect of the induced tissue hypoxia. However, an initial approach to this problem has been made by establishing the concentrations of CO and lowered inspired O<sub>2</sub> required to produce equivalent alterations in drug metabolism.
Naevocytic naevi with vascular-like spaces
Authors: G. COLLINA, V. EUSEBI
Journal: British Journal of Dermatology (1991)

Fourteen cases of naevocytic naevi with anastomising lacunae suggestive of vascular spaces are reported. The cells lining these lacunae were consistent with naevus cells, being positive for vimentin and S100 protein and negative for factor VIII-related antigen and Ulex europaeus I. The cells were not surrounded by laminin or type IV collagen. We suggest the formation of these vascular-like spaces may be due to defective production or increased degradation of components of the basement membrane with a consequent lack of cohesion.
THE PATHOLOGIC EFFECTS OF INTRAVENOUSLY ADMINISTERED SOLUBLE ANTIGEN-ANTIBODY COMPLEXES
Authors: Baruj Benacerraf, Jacobus L. Potter, Robert T. McCluskey, Frederick Miller
Journal: The Journal of Experimental Medicine (1960)

The intravenous administration to rats of soluble antigen-antibody complexes in antigen excess resulted in acute glomerulonephritis. This occurred with both rabbit antiovalbumin and rabbit anti-BSA systems. The rats so treated regularly showed proteinuria and elevation of blood urea nitrogen. These findings are compared with those reported in rats injected with anti-kidney serum.
Metoclopramide versus chlorpromazine in controlling nausea and vomiting induced by cytotoxic drugs
Authors: S G Allan, E J Bayliss, P S Warrington, R C F Leonard
Journal: BMJ (1985)

surveillance began in 1982.Among these infants, only one has been reported to have had acute cliniuall h-epatitis B in early infancy.Although the exclusion of infants of anti- HBe positive mothers from the immunisation programme has rcsulted in so little ill effect, the ability to identify a subgroup of anti- HBe positive women and to offer immunisa- tion for their infants would make it possible to prevent the rare clinical hepatitis B infection without too large an increase in numbers.However, the use of hepatitis B virus DNA hybridisation tests in place of e antigen/,antibody tests for antenatal patients must depend on assessments of cost and feasibility.
Rheumatoid Arthritis in Liberia with an Assessment of Serological Findings
Authors: W. Hijmans, H. A. Valkenburg, A. S. Muller, S. Gratama
Journal: Annals of the Rheumatic Diseases (1964)

<h3>Objective</h3> Kenyan village children are casualties to bacterial meningitis. Early diagnosis and appropriate antibiotic treatment are perhaps the most important initiatives towards eradication of this great pandemic and its management in Kenyas rural villages. The objective of this study indicates and brings to awareness that bacterial meningitis kills many children from poor and desperate Kenyan villages without access to hospitals or clinics. <h3>Methods</h3> Nyando Sub District Hospital, serving 300 000 people in a rural, malaria-pandemic area of the Western Kenyan, was studied. A Kenya Medical Research Institute research centre is located at Kisian near Kisumu city. All paediatric admissions aged 60 days between June 2001 and July 2002 were eligible. <h3>Results</h3> A total of 91(2.0%) of 4582 admissions had meningitis, including 77(4.0%) of 1929 of those who met the IMCI referral criteria for meningitis at admission (sensitivity: 85%; specificity: 59%). Independent indicators of the presence of meningitis were a bulging fontanel, neck stiffness, cyanosis, impaired consciousness, partial seizures and seizures outside the febrile convulsions age range. The area under the receiver operating characteristic curve for a set of simple screening rules based on the positive indicators identified was 0.88(95% CI 0.85 to 0.92). <h3>Conclusions</h3> The presence of one of a bulging fontanel, neck stiffness, cyanosis, impaired consciousness, partial seizures and seizures outside the febrile convulsions age range is a clear indication for lumbar puncture and/or presumptive treatment.
409 PROJECTING THE LONG-TERM CLINICAL IMPACT OF BOCEPREVIR IN PATIENTS WITH CHRONIC HEPATITIS C GENOTYPE-1 WHO FAILED PRIOR TREATMENT WITH PEGINTERFERON/RIBAVIRIN
Authors: J. Chhatwal, S.A. Ferrante, E.J. Dasbach, A. El Khoury, M. Burroughs, B. Bacon, R. Esteban-Mur, C. Brass
Journal: Journal of Hepatology (2011)
TRICHINOSIS AND ITS OCULAR MANIFESTATIONS
Authors: LELAND F. CARTER
Journal: JAMA (1930)

The observations of the ophthalmologist are of invaluable aid in the diagnosis, treatment and prognosis of many systemic and neurologic diseases. This is particularly true in regard to examination of the eyegrounds and the perimetric fields. Although he could never hope to attain this enviable degree of diagnostic precision by external examination of the eye, certainly there are times when the external appearance of the eye and its adnexa will present some of the first evidences of a grave disorder. In this category falls trichinosis, a most interesting parasitic disease which probably presents itself for diagnosis not infrequently. Because of its varied symptomatology trichinosis is, unless by chance, almost as frequently undiagnosed. This is evidenced by the comparatively few cases reported in the literature as against the observations of H. U. Williams,<sup>1</sup>who in 505 autopsies in which the disease had not previously been suspected found 5.34 per cent
OBITUARY ANNOUNCEMENTS OF DR. RUFFIN AND DR. TAYLOR
Authors: Lewis William Fetzer
Journal: JAMA (1949)

To the Editor:—  I am indeed surprised at the brevity of the the necrologies of two outstanding doctors, namely, Sterling Ruffin of Washington, D. C., and Alonzo E. Taylor of Palo Alto, Calif. Sterling Ruffin was one of Woodrow Wilson's physicians—and much more—while Alonzo Englebert Taylor was an outstanding American physiologist and food scientist.  Dr. Taylor was a member of the referee board appointed by a president of the United States, professor of physiologic chemistry of the University of Pennsylvania, professor of pathology and physiologic chemistry of the University of California, director of the Food Research Institute at Leland Stanford and a member of the Hoover Commission, in the capacity of special aid to the chief and a connecting link between the Department of Agriculture and the Food Administration. During, and in the aftermath of, the first World War, Dr. Taylor studied and learned about food conditions in Germany as
Effect of Local Medical Opinion Leaders on Quality of Care for Acute Myocardial Infarction
Authors: Stephen B. Soumerai, Thomas J. McLaughlin, Jerry H. Gurwitz, Edward Guadagnoli, Paul J. Hauptman, Catherine Borbas, Nora Morris, Barbara McLaughlin, Xiaoming Gao, Donald J. Willison, Richard Asinger, Fredarick Gobel
Journal: JAMA (1998)

Context.—The effectiveness of recruiting local medical opinion leaders to improve quality of care is poorly understood.Objective.—To evaluate a guideline-implementation intervention of clinician education by local opinion leaders and performance feedback to (1) increase use of lifesaving drugs (aspirin and thrombolytics in eligible elderly patients, β-blockers in all eligible patients) for acute myocardial infarction (AMI), and (2) decrease use of a potentially harmful therapy (prophylactic lidocaine).Design.—Randomized controlled trial with hospital as the unit of randomization, intervention, and analysis.Setting.—Thirty-seven community hospitals in Minnesota.Patients.—All patients with AMI admitted to study hospitals over 10 months before (1992-1993, N=2409) or after (1995-1996, N=2938) the intervention.Intervention.—Using a validated survey, we identified opinion leaders at 20 experimental hospitals who influenced peers through small and large group discussions, informal consultations, and revisions of protocols and clinical pathways. They focused on (1) evidence (drug efficacy), (2) comparative performance, and (3) barriers to change. Control hospitals received mailed performance feedback.Main Outcome Measures.—Hospital-specific changes before and after the intervention in the proportion of eligible patients receiving each study drug.Results.—Among experimental hospitals, the median change in the proportion of eligible elderly patients receiving aspirin was +0.13 (17% increase from 0.77 at baseline), compared with a change of −0.03 at control hospitals (P=.04). For β-blockers, the respective changes were +0.31 (63% increase from 0.49 at baseline) vs +0.18 (30% increase from baseline) for controls (P=.02). Lidocaine use declined by about 50% in both groups. The intervention did not increase thrombolysis in the elderly (from 0.73 at baseline), but nearly two thirds of eligible nonrecipients were older than 85 years, had severe comorbidities, or presented after at least 6 hours.Conclusions.—Working with opinion leaders and providing performance feedback can accelerate adoption of some beneficial AMI therapies (eg, aspirin, β-blockers). Secular changes in knowledge and hospital protocols may extinguish outdated practices (eg, prophylactic lidocaine). However, it is more difficult to increase use of effective but riskier treatments (eg, thrombolysis) for frail elderly patients.
Foxp3+ regulatory T cells protect the liver from immune damage and compromise virus control during acute experimental hepatitis B virus infection in mice
Authors: Leonhard Stross, Johannes Günther, Georg Gasteiger, Theresa Asen, Stefanie Graf, Michaela Aichler, Irene Esposito, Dirk H. Busch, Percy Knolle, Tim Sparwasser, Ulrike Protzer
Journal: Hepatology (2012)

The strength of antiviral T cell responses correlates with clearance of hepatitis B virus (HBV) infection, but the immunological mechanisms mitigating or suppressing HBV-specific T cells are still poorly understood. In this study, we examined the role of CD4+ Foxp3+ regulatory T cells (Tregs) in a mouse model of acute HBV infection. We initiated HBV infection via an adenoviral vector transferring a 1.3-fold overlength HBV genome (AdHBV) into transgenic DEREG mice, where Tregs can be transiently but selectively depleted by injection of diphtheria toxin. The effect of Treg depletion on the outcome of HBV infection was characterized by detailed virological, immunological, and histopathological analysis. Numbers of Tregs increase in the liver rapidly after initiation of HBV replication. Initial depletion of Tregs revealed their complex regulatory function during acute infection. Tregs mitigated immunomediated liver damage by down-regulating the antiviral activity of effector T cells by limiting cytokine production and cytotoxicity, but did not influence development of HBV-specific CD8 T cells or development of memory T cells. Furthermore, Tregs controlled the recruitment of innate immune cells such as macrophages and dendritic cells to the infected liver. As a consequence, Tregs significantly delayed clearance of HBV from blood and infected hepatocytes. Conclusion: Tregs limit immunomediated liver damage early after an acute infection of the liver, thereby contributing to conservation of tissue integrity and organ function at the cost of prolonging virus clearance.
Fibrosis in the transplanted heart and its relation to donor ischemic time. Assessment with polarized light microscopy and digital image analysis.
Authors: J G Pickering, D R Boughner
Journal: Circulation (1990)

Long-distance procurement of cardiac allografts is commonly used to increase the supply of donor organs but has recently been associated with the development of impaired diastolic function. Therefore, the effect of the total ischemic duration on myocardial fibrosis was quantitatively evaluated in 36 cardiac transplant recipients in whom the ischemic time ranged from 70 to 363 (mean, 189 +/- 83) minutes. Interstitial collagen was quantified with polarization microscopy and digital image analysis in 115 endomyocardial biopsy specimens taken 5-10 days after surgery. The technique, developed for this study, showed excellent correlation with hydroxyproline analysis (r = 0.98, p less than 0.001). Collagen volume fraction in biopsy specimens from the transplanted hearts was significantly greater than that in biopsy samples from seven normal, age-matched autopsy hearts (4.7 +/- 1.9% vs. 2.9 +/- 0.6%, p less than 0.02). The degree of fibrosis correlated with the total ischemic time (r = 0.60, p less than 0.001). Donor age ranged from 10 to 51 years and did not correlate with the degree of fibrosis. No relation was found between the corresponding collagen content and right atrial pressure, pulmonary artery wedge pressure, or cardiac output measured at the time of biopsy. Myocyte damage was observed in eight of the 36 patients and was characterized by a striking loss of muscle birefringence. We conclude that cardiac allograft fibrosis may be identified shortly after transplantation and is dependent on the total ischemic duration.
Evidence for a role for IL-5 and eotaxin in activating and recruiting eosinophils in drug-induced cutaneous eruptions
Authors: Nikhil Yawalkar, Maithili Shrikhande, Yvonne Hari, Helga Nievergelt, Lasse R. Braathen, Werner J. Pichler
Journal: Journal of Allergy and Clinical Immunology (2000)
885 Metalloproteinase-8 gene delivery up-regulates MMP-2, MMP-3 and induces cell proliferation in experimental liver cirrhosis
Authors: J ARMENDARIZBORUNDA, F SILLERLOPEZ, J GARCIA, A SANDOVAL, S SALGADO, A SALAZAR, E AGUILARCORDOVA
Journal: Hepatology (2003)

It is unclear how pathogenic bacteria adhere to different implant materials and whether biomarker matrix metalloproteinase-8 (MMP-8) level provides a reliable method of evaluating the connective tissue status of peri-implant tissues.The purpose of this pilot clinical study was to evaluate peri-implant connective tissue response by assessing the MMP-8 levels in peri-implant crevicular fluid around titanium and zirconia abutments.The study was designed as a prospective, within-subject comparison with left-right randomization low. Twelve participants with partial edentulism were selected according to inclusion and exclusion criteria. Peri-implant sulcal fluid sampling and pocket probing depths were assessed at 1, 3, and 12 months after placing the abutments. The MMP-8 protein level of the peri-implant sulcal fluid was determined by MMP-8-specific sandwich enzyme-linked immunosorbent assay system. The independent t test or Wilcoxon test was used to compare MMP-8 levels and probing depth assessment between the zirconia and titanium groups at different time points (1, 3, and 12 months). Repeated measures ANOVA was used for within-group comparison of the MMP-8 levels at 3 time points (α=.05).At 1 and 3 months, the titanium abutments showed significantly higher MMP-8 levels and probing depths than the zirconia abutments (P<.05), but no significant differences were found at 12 months for either variable (P>.05).This study suggests the presence of more remodeling and/or inflammatory phenomena around titanium implant abutments than around zirconia abutments of a different design during the early stages but not at 1 year.