tbuckley/cabot-search huggingface dataset:
The fungicidal mechanisms of human monocytes. I. Evidence for myeloperoxidase-linked and myeloperoxidase-independent candidacidal mechanisms.
Authors: R I Lehrer
Journal: Journal of Clinical Investigation (1975)

We tested the ability of human peripheral blood monocytes to kill Candida albicans and Candida parapsilosis. Evidence that multiple fungicidal mechanisms operate in normla monocytes was found. Normal monocytes ingested and killed viable C. albicans, and could iodinate heat-killed C. albicans. Both functions were defective in monocytes from subjects with myeloperoxidase deficiency or chronic granulomatous disease. Methimazole, isoniazid, and aminotriazole inhibited iodination by normal monocytes without impairing their ability to kill C. albicans, indicating that iodination was not essential to the myeloperoxidase-hydrogen peroxide-mediated fungicidal system of the monocyte. C. parapsilosis, an organism killed with supranormal efficacy by monocytes from a patient with hereditary myeloperoxidase deficiency, was selected to examine the myeloperoxidase-independent fungicidal mechanisms of monocytes. Monocytes were obtained from the blood of normal or leukemic subjects and homogenized in 0.34 M sucrose to yield fractions rich in cytoplasmic granules. These fractions were extracted with 0.01 M citric acid and the soluble components were separated by micropreparative polyacrylamide electrophoresis. Monocytes were found to contain cationic proteins, other than myeloperoxidase, that kill C. parapsilosis in vitro.
Risk factors for acanthamoeba keratitis in contact lens users: a case-control study
Authors: C. F Radford, A. S Bacon, J. K G Dart, D. C Minassian
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To investigate reasons for an increase in cases of Acanthamoeba keratitis related to contact lenses. <b>Design</b>: Case-control study. Cases were contact lens related acanthamoeba keratitis patients treated between 1 September 1989 and 31 August 1992. Controls were lens users without lens related disease who presented as new patients to the casualty department from 1 March 1992 to 31 August 1992. All subjects completed a questionnaire detailing lens use and hygiene practices. <b>Setting</b>: Eye hospital. <b>Subjects</b>: 35 cases with acanthamoeba keratitis and 378 controls. <b>Main outcome measures</b>: Relative risks comparing different contact lens types, socioeconomic classification, age, sex, lens use, lens wearing experience, hygiene compliance, and hygiene systems. <b>Results</b>: The crude relative risk for developing acanthamoeba keratitis with the use of daily wear disposable lenses was 49.45 (95% confidence interval 6.53 to 2227; P&lt;0.001) compared with conventional soft lenses (the referent). Multivariable analysis showed that this increased risk could be largely attributed to lack of disinfection (relative risk 55.86 (10 to 302); P&lt;0.001) and use of chlorine based disinfection (14.63 (2.8 to 76); P=0.001) compared with other chemical systems (the referent). None of the other outcome measures showed a significant association. <b>Conclusions</b>: Both failure to disinfect daily wear soft contact lenses and the use of chlorine release lens disinfection systems, which have little protective effect against the organism, are major risk factors for acanthamoeba keratitis. These risks have been particularly common in disposable lens use. Over 80% of acanthamoeba keratitis could be avoided by the use of lens disinfection systems that are effective against the organism. <h3>Key messages</h3> Key messages These risk factors are both more common in users of disposable daily wear soft lenses Over 80% of acanthamoeba infections could be eliminated by daily disinfection of reused lenses with systems effective against the organism Disinfection systems ineffective against acanthamoeba should not be licenced for use
Several New Drugs Shift Direction of Treatment and Research for HIV/AIDS
Authors: Rebecca Voelker
Journal: JAMA (1996)

THE EMERGENCE of new HIV/AIDS drugs is a double-edged sword for clinicians, pharmaceutical companies, and researchers who design and implement clinical trials. More treatment options abound, but physicians have little guidance in how to determine the best drug combinations. And while experts argue about whether clinical decisions should be based on study results using surrogate markers, such as viral load, or clinical end points of progression to AIDS or death, they tend to agree that combination therapy renders obsolete clinical trial designs that stack one agent up against AZT (zidovudine) monotherapy. "It's the best of times and the worst of times right now in this epidemic," remarked Kenneth H. Mayer, MD, director of the AIDS program at Brown University Medical School, Providence, RI, during a recent conference on clinical AIDS research. It was sponsored by Boston, Mass—based Public Responsibility in Medicine and Research, an organization devoted to ethics in research.
Deletions on der(9) chromosome in adult Ph-positive acute lymphoblastic leukemia occur with a frequency similar to that observed in chronic myeloid leukemia
Authors: G Specchia, F Albano, L Anelli, C T Storlazzi, A Zagaria, M Mancini, A Cuneo, F Pane, R Foà, F Manolelli, V Liso, M Rocchi
Journal: Leukemia (2003)
Prejunctional inhibition of cholinergic responses by prostaglandin E2 in human bronchi.
Authors: J L Ellis, N D Conanan
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The effect of prostaglandin E2 (PGE2) on cholinergic responses elicited by electrical field stimulation (EFS) (8 Hz, 1 ms, 8 V for 10 s every 100 s) of human isolated human bronchi was studied. Indomethacin (1 microM) was found to produce approximately a 100% increase in the cholinergic response. In the presence of indomethacin, PGE2 (1-300 nM) was found to concentration-dependently inhibit the cholinergic responses to EFS. A maximal inhibition was obtained with 100 nM PGE2 which produced an 80% inhibition of the cholinergic response. By contrast 100 nM PGE2 was without significant effect on the concentration response curve to exogenously added acetylcholine. The inhibitory effect of PGE2 on the EFS-induced cholinergic responses was not modified by the large conductance Ca(2+)-activated K+ channel inhibitor charybdotoxin (100 nM). These results suggest that endogenously released prostaglandins, presumably PGE2, act to inhibit cholinergic responses by a prejunctional mechanism in human isolated bronchi. In contrast to other autocoids, this inhibition does not involve the activation of large-conductance Ca(2+)-activated K+ channels.
Autoimmune Disorders of the Blood.
Authors: Scott N. Swisher
Journal: Annals of Internal Medicine (1964)

s1 February 1964Autoimmune Disorders of the Blood.Scott N. Swisher, M.D., F.A.C.P.Scott N. Swisher, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-2-328_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe disorders thought to have an autoimmune basis that involve the cells of the peripheral blood—autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, and possibly autoimmune leukopenia—are among the best known and most thoroughly studied examples of disorders in this group of disease processes. Nevertheless, major unanswered questions of pathogenesis and mechanisms of these diseases still exist. The current status of our knowledge of these three disorders are summarized briefly, and some of the newer information concerning autoimmune hemolytic anemia is presented. In particular, the mechanism of production of the nongamma type of antiglobulin reaction will be discussed, and the clinical significance... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1964Volume 60, Issue 2_Part_1Page: 328-329KeywordsAutoimmune diseasesBloodCellsHemolytic anemiaIdiopathic thrombocytopenic purpuraPathogenesis Issue Published: 1 February 1964 PDF DownloadLoading ...
Insights Into the Role of the Microbiome in Obesity and Type 2 Diabetes
Authors: Annick V. Hartstra, Kristien E.C. Bouter, Fredrik Bäckhed, Max Nieuwdorp
Journal: Diabetes Care (2014)

The worldwide prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise at an alarming pace. Recently the potential role of the gut microbiome in these metabolic disorders has been identified. Obesity is associated with changes in the composition of the intestinal microbiota, and the obese microbiome seems to be more efficient in harvesting energy from the diet. Lean male donor fecal microbiota transplantation (FMT) in males with metabolic syndrome resulted in a significant improvement in insulin sensitivity in conjunction with an increased intestinal microbial diversity, including a distinct increase in butyrate-producing bacterial strains. Such differences in gut microbiota composition might function as early diagnostic markers for the development of T2DM in high-risk patients. Products of intestinal microbes such as butyrate may induce beneficial metabolic effects through enhancement of mitochondrial activity, prevention of metabolic endotoxemia, and activation of intestinal gluconeogenesis via different routes of gene expression and hormone regulation. Future research should focus on whether bacterial products (like butyrate) have the same effects as the intestinal bacteria that produce it, in order to ultimately pave the way for more successful interventions for obesity and T2DM. The rapid development of the currently available techniques, including use of fecal transplantations, has already shown promising results, so there is hope for novel therapies based on the microbiota in the future.
Insulin Binding to Its Receptor: Is the Receptor More Important Than the Hormone?
Authors: Jesse Roth
Journal: Diabetes Care (1981)

The development of methods to measure insulin showed that many (if not most) patients with disorders of glucose metabolism have a target cell disorder rather than a secretory defect. Methods to measure the insulin receptor have shown that in patients with target cell disorders the receptor is often involved in a meaningful way. Furthermore, even in diseases where hormone secretion (deficiency or excess) is dominant, the receptor may play an important role in the clinical state of the patients. In the future, development of techniques to assess postreceptor events should uncover defects at these sites as well.
THE ANTRUM OF HIGHMORE IN ITS RELATION TO VOCAL RESONANCE.Read by title in the Section on Oral and Dental Surgery, at the Forty-fifth Annual Meeting of the American Medical Association, held at San Francisco, June 5-8, 1894.
Authors: W. XAVIER SUDDUTH
Journal: JAMA (1894)

Any deviation from certain well-known points of design in the construction of a musical instrument is liable to result in failure. Maker and musician have long vied with each other in their efforts to suggest modifications and improvements without materially altering the original form, which consists of a vibrating body re-inforced by sounding-boards or resonant cavities in endless variety. They are all, however, poor copies of the original instrument, the human harmonium. While musical literature abounds with accurate scientific descriptions of musical instruments in general, next to nothing can be found regarding the science and art of voice melody and oratory, and still less treating of the design of the organs themselves. The pianist, as he skilfully runs over the keyboard of an instrument, quickly perceives its good or bad points and indicates them with a degree of precision that clearly shows a knowledge of its construction. The expert organist
Mobilisation after myocardial infarction.
Authors: R Stott, S Joyce
Journal: BMJ (1977)

some studies.As an example of a possible relationship between malignant lymphoma and PMR on this ground they refer to a case described by usI in which malignant lymphoma occurred four years after the diagnosis of PMR was made.Among our 54 patients with PMR we have recently reported another case', in which chronic lymphatic leukaemia developed five years after the onset of typical PMR.In this patient lymphocytic infiltration was detected in renal, liver, and muscle biopsy specimens at the time of diagnosis of PMR, when the number of lymphocytes in the peripheral blood and bone marrow was normal.The significance of the combination of the two diseases in this patient is unclear.It may simply be the coincidental coexistence of two diseases, both relatively common in elderly people.However, the clinical course does point to a more direct relationship.Histocompatibility antigens have been studied in patients with chronic lymphatic leukaemia, but, so far as I know, no increase in any specific HLA haplotype has been shown.
Abstract S4-6: Neoadjuvant Chemotherapy with or without Bevacizumab: Primary Efficacy Endpoint Analysis of the GEPARQUINTO Study (GBG 44)
Authors: G von Minckwitz, H Eidtmann, M Rezai, PA Fasching, H Tesch, H Eggemann, I Schrader, K Kittel, C Hanusch, R Kreienberg, C Solbach, B Gerber, C Jackisch, G Kunz, J-U Blohmer, J Huober, M Hauschild, T Fehm, S Loibl, V Nekljudova, M. Untch
Journal: Cancer Research (2010)

Abstract Background: The anti-VEGF-receptor antibody bevacizumab (Bev) showed increased response rates and prolonged progression-free survival in combination with anthracyclines (A) and taxanes (T) in metastatic breast cancer (BC). One primary aim of the GeparQuinto phase III study was to improve pathological complete response (pCR) by adding Bev to AT-based neoadjuvant chemotherapy. We previously reported interim safety data showing more leukopenia, infections, mucositis, and hypertension, but less edema for the combination with Bev (von Minckwitz G et al, Ann Oncol 2010 in press). Patients and Methods: Patients (P) with untreated HER2-negative BC were eligible if they had cT3/4a-d; or estrogen (ER) and progesterone (PgR) receptor-negative; or ER/PgR-positive tumors with clinically N+ (for cT2) or pNSLN+ (for cT1) disease, and no increased cardiac or bleeding risks. P were randomized to receive 4 cycles epirubicin/cyclophosphamide (EC) (90/600 mg/m2) q3w followed by 4 cycles docetaxel (D) (100mg/m2) with or without concomitant Bev 15mg/kg q3w added to chemotherapy cycles. P not clinically responding to EC ± Bev were considered as treatment failures and entered another part of the protocol. pCR was defined as no invasive or non-invasive tumor residuals in breast and nodes. We assumed a pCR rate of 14% (based on GeparDuo) and expected a pCR of 18.9% for EC-D+Bev (odds ratio 1.43). A two-sided Pearson's Chi2 with α=0.05 and β=0.20 calculated a sample size of 1934 P. Results: Between 05/07 and 06/10 1889 P were randomized to EC-D (N=944) and EC-D+Bev (N=945). Median tumor size was 40/40 [-Bev/+Bev] mm (clinically) and 29/29 mm (sonographically); 6.3%/5.8% had T4a-c, 6.6%/6.7% T4d, 2.0%/2.1% bilateral, 14.3%/13.8% multifocal, and 8.8%/10.0% multicentric disease, 89.3%/88.9% had non-lobular, 42.5%/43.3% grade 3, 57.1%/58.4% node-positive, and 34.5%/33.6% ER and PgR-negative (triple-negative) disease. So far, 24% and 17% of patients did not respond to the first 4 cycles of EC-Bev and EC+Bev, respectively, and discontinued randomized treatment. The last randomized P will have surgery early Dec'10. Results on histological response and surgical outcome will be reported. Conclusion: The GeparQuinto trial will provide for the first time randomized phase III efficacy data on Bev in combination to chemotherapy for patients with early breast cancer. pCR after Bev treatment can be considered as a surrogate marker for long term outcome but this has to be examined during further follow up of the patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S4-6.
The residual normality assumption and models of cognition in schizophrenia
Authors: Ruth Condray, Stuart R. Steinhauer
Journal: Behavioral and Brain Sciences (2002)

Thomas &amp; Karmiloff-Smith’ (T&amp;K-S’) argument that the Residual Normality assumption is not valid for developmental disorders has implications for models of cognition in schizophrenia, a disorder that may involve a neurodevelopmental pathogenesis. A limiting factor for such theories is the lack of understanding about the nature of the cognitive system (modular components versus global processes). Moreover, it is unclear how the proposal that modularization emerges from developmental processes would change that fundamental question.
Survival after extremely preterm birth
Authors: Neena Modi
Journal: BMJ (2008)

eDITORIaLS Smoking cessation in primary careEvidence does not support routine use of combination therapy with nortriptyline being looked at by the Neonatal Data Analysis Unit. 8 The unit was formed to support and develop the use of electronic clinical data for audit, service evaluation, surveys, and research.It is only with information on appropriately case mix adjusted outcomes in near contemporaneous cohorts that parents, clinicians, and governments will be able to make truly informed decisions.
Early posthypoglycemic insulin resistance in man is mainly an effect of beta-adrenergic stimulation.
Authors: S Attvall, B M Eriksson, J Fowelin, H von Schenck, I Lager, U Smith
Journal: Journal of Clinical Investigation (1987)

The insulin effect following hypoglycemia was studied with the euglycemic clamp technique in seven healthy subjects. Following an initial euglycemic clamp hypoglycemia was induced and after glucose recovery a second clamp was performed. Glucose production (Ra) and utilization (Rd) were studied with [3-3H]glucose. Each subject was studied four times; during infusion of placebo, propranolol, somatostatin, and a control study where hypoglycemia was prevented. Hypoglycemia induced an insulin resistance with a lower steady state glucose infusion rate following the hypoglycemia during placebo as compared to the control study (2.5 +/- 0.5 and 4.8 +/- 1.0 mg/kg min, respectively, P less than 0.05). The insulin resistance was due to an attenuated insulin effect on both inhibition of Ra (impaired by 37%) and stimulation of Rd (impaired by 61%). The insulin-antagonistic effect was completely prevented by propranolol but only partly by somatostatin. Thus, early posthypoglycemic insulin resistance (2.5-3.5 h after hypoglycemia) is a sustained effect mainly due to beta-adrenergic stimulation.
Mechanism for fetal hemoglobin induction by hydroxyurea in sickle cell erythroid progenitors
Authors: B. Surendra Baliga, Betty S. Pace, Hsueh-Hua Chen, Arvind K. Shah, Yih-Ming Yang
Journal: American Journal of Hematology (2000)

Hydroxyurea (HU) is a widely used cytotoxic agent that is known to induce fetal hemoglobin (HbF) production and is presently used to ameliorate the severity of pain episodes in patients with sickle cell anemia (HbSS). Previously we have shown that HU inhibits growth of burst forming unit-erythroid (BFU-E) colonies in a dose-dependent manner, while fetal hemoglobin levels were increased. In the present report, we extended our analysis demonstrating the number of S phase cells is significantly higher for HbSS patients that respond to HU therapy. Studies were completed in vitro using erythroid progenitors derived from umbilical cord samples or peripheral blood from patients with HbS-hereditary persistence of fetal hemoglobin (HbS-HPFH) or HbSS disease. The effect of HU on (a) S phase erythroid progenitors, (b) BFU-E colony growth, (c) HbF levels in BFU-E colonies, and (d) total cellular RNA synthesis was analyzed in vitro for the three groups. The level of S phase erythroid progenitors was similar for all three groups and BFU-E colony growth was inhibited 92-94% for all samples in a dose-dependent manner. The HbF levels were increased in BFU-E colonies from HbSS patients (control, 4.0% +/- 1.15% vs. +HU, 22.67% +/- 2.03%) whereas HbF levels were decreased in BFU-E colonies derived from umbilical cord samples (control, 80% +/- 9.07% vs. +HU, 35.7% +/- 4.81%) or HbS-HPFH patients (control, 49.67% +/- 3.84% vs. +HU, 23.3% +/- 0.88%). Total RNA synthesis measured by 3H-uridine incorporation increased with increasing concentrations of HU; however, actinomycin D inhibited HU-induced RNA synthesis. These results suggest that HU can inhibit an active globin gene without preference and that newly synthesized RNA is under transcriptional control mechanisms.
ARE CLINICAL MEASURES OF CERVICAL SPINE STRENGTH AND CERVICAL FLEXOR ENDURANCE RISK FACTORS FOR CONCUSSION IN ELITE YOUTH ICE HOCKEY PLAYERS?
Authors: K Schneider, CA Emery, J Kang, W Meeuwisse
Journal: British Journal of Sports Medicine (2014)

Background Symptoms of dizziness, neck pain and headaches have previously been identified as risk factors for concussion. Clinical measures associated with these symptoms have not previously been evaluated as risk factors for concussion. Objectives To evaluate clinical measures of cervical endurance and strength as risk factors for concussion in elite youth ice hockey players. Design Prospective cohort study. Setting Community ice rinks and Sport Medicine Clinic. Participants Bantam (12-14 years) and Midget (15–17 years) male and female elite youth ice hockey players (n=466). Risk factor assessment Participants completed baseline clinical tests of cervical flexor endurance and cervical spine isometric strength at the beginning of the 2011–2012 season. Main outcome measurements Players with a suspected concussion (identified by team therapists) were referred to the study sport medicine physician for assessment (diagnosed as per the 3 rd International Consensus on Concussion in Sport Guidelines). Results Concussion incidence rate ratios were estimated using Poisson regression (adjusted for cluster by team and exposure hours). 466 elite youth ice hockey players completed clinical baseline tests at the start of the 2011–2012 hockey season. Players performing in the lowest 25 th percentile were not at an increased risk of concussion during the season of play [cervical strength right sided IRR=1.33 (95%CI; 0.98–1.83); left IRR=1.07 (95% CI; 0.64–1.78] or cervical flexor endurance [IRR=1.27 (95% CI; 0.74–2.20)]. Conclusion Clinical tests of cervical flexor endurance and isometric cervical strength were not predictive of concussion risk. Further evaluation of other baseline clinical measures is necessary to inform future development of prevention strategies for concussion in youth.
Clinical Research on Out-of-Hospital Emergency Care
Authors: Terence D. Valenzuela, Michael K. Copass
Journal: New England Journal of Medicine (2001)

Status epilepticus is a series of successive grand mal seizures lasting minutes or even hours, without the recovery of normal consciousness. The resulting metabolic derangement of cells, depletion of the oxygen and glucose necessary for normal functioning, and disruption of ion transport across cell membranes injure neurons and damage the brain.1 The long-term complications include focal neurologic deficits, epilepsy, and encephalopathy. The longer an episode of status epilepticus lasts, the greater the risk and extent of these serious sequelae.2 Although status epilepticus has diverse causes (e.g., medication or alcohol withdrawal, preexisting epilepsy, head injury, stroke, intracranial mass, meningitis, and drug . . .