tbuckley/cabot-search huggingface dataset:
A Preliminary Trial of the Programmable Implantable Medication System for Insulin Delivery
Authors: Christopher D. Saudek, Jean-Louis Selam, Henry A. Pitt, Kenneth Waxman, Michelle Rubio, Nathalie Jeandidier, Dee Turner, Robert E. Fischell, M. Arthur Charles
Journal: New England Journal of Medicine (1989)

We undertook a trial to determine whether an implanted insulin-delivery system, the programmable implantable medication system (PIMS), could be used to treat patients with insulin-dependent diabetes. PIMS is a pulsatile, programmable pump with a battery life expectancy of five years. The reservoir is refilled transcutaneously every two months with a surfactant-stabilized human insulin preparation containing 400 U of insulin per milliliter. Eighteen patients received PIMS-delivered insulin for 4 to 25 months (mean, 18). The total PIMS-implantation experience comprised 28 patient-years. Good glycemic control was established and sustained during treatment (mean plasma glucose level, 7.3 mmol per liter; mean glycohemoglobin level, 8 percent [upper limit of normal, 7.5 percent]), with significantly reduced glycemic fluctuations. The total mean daily insulin dose did not change. Insulin solutions withdrawn from the pump reservoirs contained 92 percent native insulin and preserved biologic activity. There were no surgical or skin complications, severe hypoglycemic episodes, or instances of diabetic ketoacidosis. One pump was replaced because of a manufacturing defect, and four patients had catheter blockages due to omental-tissue encapsulation; two withdrew from the study and two had devices that were repaired successfully. The actuarial rate of survival of catheter function was 78 percent at 1.5 years. We conclude from this pilot study that insulin treatment with an implanted, variable-rate, programmable pump is feasible for periods up to two years. (N Engl J Med 1989; 321:574–9.)
Acquired Resistance to a New Alk Inhibitor, Alectinib in Lung Cancer
Authors: H. Isozaki, E. Ichihara, K. Ohashi, N. Ochi, M. Yasugi, T. Kubo, D. Minami, H. Yamane, A.H. Sato, K. Kudo, Y. Kato, K. Hotta, N. Takigawa, T. Sendo, M. Tanimoto, K. Kiura
Journal: Annals of Oncology (2014)
Superiority of Adriamycin-14-octanoate Over Adriamycin in Reducing Viability of Methotrexate-Resistant L5178Y Cells: Brief Communication
Authors: Bridget T. Hill, L A. Price
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Superiority of Adriamycin-14-octanoate Over Adriamycin in Reducing Viability of Methotrexate-Resistant L5178Y Cells: Brief Communication Get access Bridget T. Hill, Bridget T. Hill 2The Imperial Cancer Research Fund Laboratories, Lincoln's Inn Fields, London WC2A 3PX, England. Search for other works by this author on: Oxford Academic PubMed Google Scholar L A. Price L A. Price 3The Institute of Cancer Research, The Royal Marsden Hospital, Fulham Rd., London SWS 6JJ, England. 4We acknowledge the valuable technical assistance of Mr. D. Brodie and Mr. R. D. Whelan. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 4, October 1977, Pages 1311–1313, https://doi.org/10.1093/jnci/59.4.1311 Published: 01 October 1977 Article history Received: 01 September 1976 Revision received: 08 March 1977 Accepted: 02 April 1977 Published: 01 October 1977
Peanut and Arah2 Specific Immunoglobulin E Is Predictive of Sustained Unresponsiveness Following Peanut Oral Immunotherapy
Authors: Alanna J. Hickey, Yamini Virkud, Cecilia Washburn, Neal Smith, Sarita U. Patil, Wayne Shreffler
Journal: Journal of Allergy and Clinical Immunology (2016)
Relationship Between Immunologic Maturation and Viral Oncogenesis in Hamsters&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Herman Friedman, Herman Goldner
Journal: JNCI Journal of the National Cancer Institute (1970)

The development of immunocompetence to sheep erythrocytes (S-RBC) was studied in hamsters and related to susceptibility of the animals to tumor induction by adenovirus 12 and simian virus 40 (SV40). Both normal and virus-infected hamsters were challenged with S-RBC at 1, 2, 3, 4, or 6 weeks of life, and the number of antibody plaque-forming cells (PFC) was determined by the localized hemolytic plaque technique in cigar gel. Normal control hamsters formed very few splenic antibody plaques when immunized at 1 week of age. Immunoresponsiveness increased rapidly thereafter so that, by the 3d–4th week of age, relatively large numbers of antibody forming cells appeared after S-RBC immunization. Nonimmune hamsters had very few “background” PFC until the 2d–4th week of life. Inoculation of test hamsters at birth with either SV40 or adenovirus 12 had little or no effect on the capacity of the animals to respond subsequently to S-RBC at 3 or 4 weeks of age. The number of PFC was moderately depressed when challenged at 1 and 2 weeks of age, as compared to noninfected controls. There was no detectable effect on development of background PFC to S-RBC. Susceptibility to tumorigenesis was directly related to the age of the animal at infection. More than 95% of the animals inoculated before 3 days old developed tumors between 90 and 150 days of age. About 20–25% of the hamsters developed tumors when infected at 1 or 2 weeks of age, and none developed tumors with either virus when 3 weeks old or older.
Brain Neurotransmitters in Dystonia Musculorum Deformans
Authors: Oleh Hornykiewicz, Stephen J. Kish, Lawrence E. Becker, Irene Farley, Kathleen Shannak
Journal: New England Journal of Medicine (1986)

We examined histologically and biochemically the brains of two patients with generalized childhood-onset dystonia musculorum deformans. We found no important histologic changes in the basal ganglia, cerebral cortex, higher brain-stem nuclei, locus ceruleus, or raphe nuclei. Similarly, the activity of choline acetyltransferase and the levels of gamma-aminobutyric acid and glutamic acid in the cerebral cortex and basal ganglia were within the control range. In contrast, the norepinephrine concentrations were markedly and consistently decreased in the lateral and posterior hypothalamus, mamillary body, subthalamic nucleus, and locus ceruleus. The serotonin level was subnormal in the dorsal raphe nucleus, as was the dopamine level in the nucleus accumbens and, in one of the two cases, in the striatum. Elevated concentrations of norepinephrine were found in the septum, thalamus, colliculi, red nucleus, and dorsal raphe nucleus; of serotonin, in the globus pallidus, subthalamic nucleus, and locus ceruleus; and of 5-hydroxyindoleacetic acid, in the globus pallidus, subthalamic nucleus, and nuclei raphe centralis inferior and obscurus. The level of homovanillic acid showed little consistent change in the regions examined. We conclude that some of these monoamine changes, especially the pronounced apparent disturbance of noradrenergic brain mechanisms, may represent a basic neurochemical abnormality in dystonia musculorum deformans and may thus be relevant to the pathoneurophysiology and treatment of this disorder.
Asymptomatic Carriage of<i>Clostridium difficile</i>and Serum Levels of IgG Antibody against Toxin A
Authors: Lorraine Kyne, Michel Warny, Amir Qamar, Ciarán P. Kelly
Journal: New England Journal of Medicine (2000)

Clostridium difficile infection can result in asymptomatic carriage, mild diarrhea, or fulminant pseudomembranous colitis. We studied whether antibody responses to C. difficile toxins affect the risks of colonization, diarrhea, and asymptomatic carriage.
Discovery of Clinically Approved Agents That Promote Suppression of Cystic Fibrosis Transmembrane Conductance Regulator Nonsense Mutations
Authors: Venkateshwar Mutyam, Ming Du, Xiaojiao Xue, Kim M. Keeling, E. Lucile White, J. Robert Bostwick, Lynn Rasmussen, Bo Liu, Marina Mazur, Jeong S. Hong, Emily Falk Libby, Feng Liang, Haibo Shang, Martin Mense, Mark J. Suto, David M. Bedwell, Steven M. Rowe
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Premature termination codons (PTCs) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). Several agents are known to suppress PTCs but are poorly efficacious or toxic.Objectives: To determine whether there are clinically available agents that elicit translational readthrough and improve CFTR function sufficient to confer therapeutic benefit to patients with CF with PTCs.Methods: Two independent screens, firefly luciferase and CFTR-mediated transepithelial chloride conductance assay, were performed on a library of 1,600 clinically approved compounds using fisher rat thyroid cells stably transfected with stop codons. Select agents were further evaluated using secondary screening assays including short circuit current analysis on primary cells from patients with CF. In addition, the effect of CFTR modulators (ivacaftor) was tested in combination with the most efficacious agents.Measurements and Main Results: From the primary screen, 48 agents were selected as potentially active. Following confirmatory tests in the transepithelial chloride conductance assay and prioritizing agents based on favorable pharmacologic properties, eight agents were advanced for secondary screening. Ivacaftor significantly increased short circuit current following forskolin stimulation in cells treated with pyranoradine tetraphosphate, potassium p-aminobenzoate, and escin as compared with vehicle control. Escin, an herbal agent, consistently induced readthrough activity as demonstrated by enhanced CFTR expression and function in vitro.Conclusions: Clinically approved drugs identified as potential readthrough agents, in combination with ivacaftor, may induce nonsense suppression to restore therapeutic levels of CFTR function. One or more agents may be suitable to advance to human testing.
M8 Prevalence of respiratory disease in severe morbid obesity
Authors: SIW Lipworth, T Thevanathan, SW Copack, J Emmanuel
Journal: Thorax (2015)

<h3>Introduction</h3> It is well established that asthma and obstructive sleep apnoea (OSA) are significantly more prevalent in obese vs. non-obese populations. To date however there is limited data on whether this risk is increased with severity of obesity as most studies classify all patients &gt;30 Kg/m<sup>2</sup> simply as ‘obese’. In addition, many existing studies’ obese cohorts have fairly low BMI scores compared to patients attending specialist medical obesity services. Our study aims to examine the prevalence of these diseases in higher BMI groups, compare the relative risk of increasing obesity on prevalence of respiratory disease and investigate whether there is a synergistic effect of multiple demographic factors and severity of obesity. <h3>Methods</h3> Data was collected from a total of 367 (of whom 159 had a BMI recorded) patient records attending a tier 4 obesity clinic over an 8 month period. Patients were divided into three groups according to severity of obesity, BMI 30–40, 40–50 and &gt;50 Kg/m<sup>2</sup>. Index of multiple deprivation (IMD) scores (mapped to postcodes) were used as a proxy of socioeconomic status. <h3>Results</h3> 43% of our total cohort had OSA, including 75.7% of those with a BMI &gt;50 (Multivariate logistic regression OR 10.4 (95% CI 3.33 – 32.7, p &lt; 0.001). In a chi-square analysis, this association was significant in both genders but stronger in males (Cramer’s V 0.481 vs 0.305) and was significantly associated with a worse IMD score, being white and increasing age. 11.6% of the cohort were asthmatic however there was no difference in prevalence between the groups OR 0.175 (95% CI 0.019 – 1.631, p = 0.126). There was however a significant co-effect of being male and increasing BMI in a multi-layer chi-square analysis p = 0.044. <h3>Conclusions</h3> Our study highlights a very high prevalence of major respiratory diseases as co-morbidities in a severely obese population. Early data suggests a synergistic effect of Caucasian ethnicity, male gender and IMD score with increasing BMI on the risk of developing OSA (and Asthma for male gender). This is in contrast with our initial findings for Diabetes and Cardiovascular disease where the association is with Asian ethnicity.
Application of Endonuclease Mapping to the Analysis and Prenatal Diagnosis of Thalassemias Caused by Globin-Gene Deletion
Authors: Stuart H. Orkin, Blanche P. Alter, Cigdem Altay, Maurice J. Mahoney, Herbert Lazarus, John C. Hobbins, David G. Nathan
Journal: New England Journal of Medicine (1978)

We applied a recently developed and more direct technic to diagnose thalassemia syndromes associated with deletion of particular globin structural genes and to assess a fetus at risk for one of those conditions, deltabeta-thalassemia. The method allows assessment of the globin genes present in total cellular DNA and is applicable to amniotic-fluid cell DNA. Cellular DNA fragments produced by cleavage using two specific restriction endonucleases are separated on the basis of size by agarose-gel electrophoresis, and the distribution of specific sequences among the DNA fragments determined by molecular hybridization. We observed the total deletion of alpha-globin genes in homozygous alpha-thalassemia (hydrops fetalis with hemoglobin Bart's) and the deletion of particular beta and beta-like sequences in cases homozygous for hereditary persistence of fetal hemoglobin and deltabeta-thalassemia. Analysis of amniotic-fluid cell DNA from a fetus at risk for deltabeta-thalassemia demonstrated the feasibility of these improved methods for antenatal diagnosis. The molecular studies confirmed the diagnosis predicted by analysis of fetal blood and established at birth.
Induction of Bladder Tumors and Other Malignancies in Rats With 2-Methoxy-3-Aminodibenzofuran&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Jack L. Radomski, Earl Brill, Elliot M. Glass
Journal: JNCI Journal of the National Cancer Institute (1967)

When fed for a maximum of 75 weeks at a level of 0.1% in the diet, 2-methoxy-3-aminodibenzofuran induced malignant or benign neoplastic changes of the bladder transitional cells in 41.7% of 72 rats. Eleven of these (15.3%) had transitional cell carcinomas. 2-Methoxy-3-aminodibenzofuran also induced mammary adenocarcinomas and tumors in the external auditory canal. There was little difference in carcinogenicity of the compound in the Sprague-Dawley, Wistar, or Fischer strains. One instance of metastasis of a transitional cell carcinoma to the kidney end lung was observed. The synthesis, purification, and chromatographic characteristics of 2-methoxy-3-aminodibenzofuran are given.
Phase I study of the safety and pharmacokinetics (PK) of paclitaxel or paclitaxel with carboplatin administered in combination with pazopanib (GW786034)
Authors: B. Suttle, S. Jones, A. Dowlati, A. Tan, C. Mauser, K. Taber, D. Gibson, T. Arumugham, J. J. Lager, H. A. Burris
Journal: Journal of Clinical Oncology (2007)

14118 Background: Pazopanib is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/β, and c-kit. Pazopanib also is a moderate inhibitor of CYP2C8 and CYP3A4 in vitro. Paclitaxel (T), a substrate for CYP2C8 and CYP3A4, administered alone and in combination with carboplatin (Cb) is highly active in breast, NSCLC, and ovarian cancers. The additive benefit of the anti-VEGF agent bevacizumab with T or T-Cb in breast and NSCLC provides strong rationale for use of a multi-targeted TKI with T or T-Cb. Methods: Pts with advanced cancer (ECOG PS 0–1) were eligible. Dose escalation was split into Part 1 [T (15–80 mg/m 2 ) days 1, 8, 15 q 28 days plus pazopanib (400–800 mg) QD starting on day 2 of cycle 1] and Part 2 [T (80- 225 mg/m 2 ) plus Cb AUC 6 q 21 days plus pazopanib 800 mg QD starting on day 2 of cycle 1]. Safety, PK, and clinical response were evaluated. Dose escalation occurred in cohorts of 3–6 pts based on dose-limiting toxicities (DLTs) and PK. Results: 12 pts in Part 1 received the following pazopanib/T doses (n = pts): 400 mg/15 mg/m 2 (3), 800 mg/15 mg/m 2 (3), 800mg /50 mg/m 2 (3), 800mg /80 mg/m 2 (3). Preliminary data were available from 9 pts in Part 1. Selected mean PK results for T are shown. 4 pts in Part 2 received 800mg /175 mg/m 2 /AUC 6 of pazopanib/T/Cb (data not yet available). Most common AEs (&gt;20%) in Part 1 were Gr 1/2 and consisted of fatigue, diarrhea, anorexia, nausea, vomiting, dysgeusia, AST elevation, rash, hypertension, and cough; Gr 3 diarrhea was reported in 1 pt. The 800mg pazopanib/80 mg/m 2 T cohort in Part 1 is being expanded to 6 pts due to a DLT (dose delay of &gt; 2 wks due to an abscess). Best response (n=6 pts) in Part 1 was SD (83%) (range 1–5 cycles). Conclusions: Concomitant administration of pazopanib increased paclitaxel mean Cmax and AUC(0–8) approximately 20–35%. Determination of the MTR in Parts 1 and 2 is ongoing. These findings warrant further studies at therapeutic doses of pazopanib, paclitaxel, and carboplatin. [Table: see text] No significant financial relationships to disclose.
US military prepares to punish soldiers who attacked MSF hospital
Authors: Owen Dyer
Journal: BMJ (2016)

A military investigation into a US airstrike on a hospital run by Medecins Sans Frontieres in Kunduz, Afghanistan, last October, which left 42 civilians dead, has recommended disciplinary action against the soldiers involved in the attack.

John Campbell, a general in the US army and commander of North Atlantic Treaty Organization forces in Afghanistan, has forwarded a 3000 page report to US Central Command with his recommendations for disciplinary action, Foreign Policy magazine has reported.

Anonymous congressional staff and defence officials told Foreign Policy that the investigation focused on the US Army Green Beret unit on the ground near the hospital that called in the airstrike. A colonel and two major generals higher up the chain of command also drew scrutiny. MSF …
Some Effects of Aqueous Extracts of Acetone-Dried Beef-Pineal Substance in Chronic Schizophrenia
Authors: Mark D. Altschule
Journal: New England Journal of Medicine (1957)

EARLIER work from this laboratory showed that certain beef-pineal extracts reversed some of the biochemical abnormalities encountered in schizophrenic patients.1 Clinical improvement also was noted in those earlier studies; this finding accorded with that previously reported by other authors who had used pineal extracts in schizophrenia.2 This report describes some effects of several different aqueous extracts made from acetone-dried beef pineal glands.ObservationsEffects of Simple Aqueous Extracts Alone (Improvement Followed by Refractoriness)An extract was made by mixture of the powder derived from acetone-dried beef-pineal substance with distilled water in a Waring blendor, 10 ml. of water for each . . .
The influence of a short-term gluten-free diet on the human gut microbiome
Authors: Marc Jan Bonder, Ettje F. Tigchelaar, Xianghang Cai, Gosia Trynka, Maria C. Cenit, Barbara Hrdlickova, Huanzi Zhong, Tommi Vatanen, Dirk Gevers, Cisca Wijmenga, Yang Wang, Alexandra Zhernakova
Journal: Genome Medicine (2016)

A gluten-free diet (GFD) is the most commonly adopted special diet worldwide. It is an effective treatment for coeliac disease and is also often followed by individuals to alleviate gastrointestinal complaints. It is known there is an important link between diet and the gut microbiome, but it is largely unknown how a switch to a GFD affects the human gut microbiome. We studied changes in the gut microbiomes of 21 healthy volunteers who followed a GFD for four weeks. We collected nine stool samples from each participant: one at baseline, four during the GFD period, and four when they returned to their habitual diet (HD), making a total of 189 samples. We determined microbiome profiles using 16S rRNA sequencing and then processed the samples for taxonomic and imputed functional composition. Additionally, in all 189 samples, six gut health-related biomarkers were measured. Inter-individual variation in the gut microbiota remained stable during this short-term GFD intervention. A number of taxon-specific differences were seen during the GFD: the most striking shift was seen for the family Veillonellaceae (class Clostridia), which was significantly reduced during the intervention (p = 2.81 × 10−05). Seven other taxa also showed significant changes; the majority of them are known to play a role in starch metabolism. We saw stronger differences in pathway activities: 21 predicted pathway activity scores showed significant association to the change in diet. We observed strong relations between the predicted activity of pathways and biomarker measurements. A GFD changes the gut microbiome composition and alters the activity of microbial pathways.
Tartrate-Resistant Acid Phosphatase Isoenzyme in the Reticulum Cells of Leukemic Reticuloendotheliosis
Authors: L. T. Yam, C. Y. Li, K. W. Lam
Journal: New England Journal of Medicine (1971)

Acid phosphatase activity in the reticulum cells of leukemic reticuloendotheliosis is quantitatively and qualitatively different from that in the lymphosarcoma cells of lymphosarcoma and in lymphocytes of chronic lymphocytic leukemia. Enzyme activity in the reticulum cells is strong and tartrate resistant, whereas that in the lymphoid cells of the other two diseases is very weak and is inhibited by tartrate. A combined cytochemical and electrophoretic study indicates that this tartrate-resistant enzyme activity represents isoenzyme 5. It is present almost exclusively in the reticulum cells and not in other hemic cells in leukemic reticuloendotheliosis. It is not present in the lymphoid cells in lymphosarcoma or chronic lymphocytic leukemia. It may be used as the marker enzyme to diagnose leukemic reticuloendotheliosis and to trace the origin of the "reticulum cells" ("hairy cells") in the reticuloendothelial system.