tbuckley/cabot-search huggingface dataset:
Climate Variability and Change and Their Potential Health Effects in Small Island States: Information for Adaptation Planning in the Health Sector
Authors: Kristie L. Ebi, Nancy D. Lewis, Carlos Corvalan
Journal: Environmental Health Perspectives (2006)

Small island states are likely the countries most vulnerable to climate variability and longterm climate change. Climate models suggest that small island states will experience warmer temperatures and changes in rainfall, soil moisture budgets, prevailing winds (speed and direction), and patterns of wave action. El Niño events likely will strengthen shortterm and interannual climate variations. In addition, global mean sea level is projected to increase by 0.09-0.88 m by 2100, with variable effects on regional and local sea level. To better understand the potential human health consequences of these projected changes, a series of workshops and a conference organized by the World Health Organization, in partnership with the World Meteorological Organization and the United Nations Environment Programme, addressed the following issues: the current distribution and burden of climate-sensitive diseases in small island states, the potential future health impacts of climate variability and change, the interventions currently used to reduce the burden of climate-sensitive diseases, additional interventions that are needed to adapt to current and future health impacts, and the health implications of climate variability and change in other sectors. Information on these issues is synthesized and key recommendations are identified for improving the capacity of the health sector to anticipate and prepare for climate variability and change in small island states.
Psychosocial Effects of Intestinal Bypass Surgery for Severe Obesity
Authors: Charles Solow, Peter M. Silberfarb, Katharine Swift
Journal: New England Journal of Medicine (1974)

The psychosocial consequences of intestinal bypass surgery and weight loss were observed in 29 massively obese patients. The response to weight loss, as assessed by both semistructured psychiatric interviews and a series of self-administered questionnaires, was an improvement in mood, self-esteem, interpersonal and vocational effectiveness, body image and activity levels, as well as a notable decrease in the use of denial. The decrease in depression and improvements in ego strength, body image and global clinical rating of psychologic status were directly proportional to the magnitude of weight loss. The most important psychologic change responsible for improved functioning was the loss of a pervasive sense of entrapment, helplessness and failure associated with massive obesity. There is evidence that the relative unresponsiveness of obese patients to the internal cues associated with satiety is reversible with weight loss. Symptom substitution did not occur. The reversibility of many of the psychosocial disturbances associated with severe obesity supports the view that they are as much the consequences as the causes of excessive adiposity. (N Engl J Med 290:300–304, 1974)
In Vivo Immunologic Selection of Class I Major Histocompatibility Complex Gene Deletion Variants From the B16-BL6 Melanoma<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: J E Talmadge, C B Talmadge, B Zbar, R McEwen, A K Meeker, H Tribble
Journal: JNCI Journal of the National Cancer Institute (1987)

The mechanism by which tumor allografts escape host immunologic attack was investigated. B16-BL6 cells (the bladder 6 subline of the B16 melanoma) (H-2b) were transfected with a gene (Dd) encoding an allogeneic class I major histocompatibility complex antigen. Clones that expressed Dd antigen were injected into the footpads of nonimmune syngeneic mice, syngeneic immune mice, and nude mice. Under conditions of immunologic selection a clone that contained multiple copies of the transfected gene formed variants that lacked the transfected gene. Primary tumors and pulmonary metastases of immunized mice and pulmonary metastases of nonimmunized mice had lost the Dd gene and, in most cases, all of the associated plasmid. In contrast, in immunodeficient nude mice, primary tumors and pulmonary metastases retained the Dd gene and the associated plasmid. Deletion of genes encoding cell surface antigens may be one of the mechanisms by which allogeneic tumors escape immunologic attack.
Salvage chemotherapy with rituximab DHAP (RDHAP) for relapsed non-hodgkin lymphoma (NHL): A phase II trial in the North Central Cancer Treatment Group
Authors: T. E. Witzig, S. M. Geyer, P. J. Kurtin, J. P. Colgan, D. J. Inwards, I. N. Micallef, J. C. Michalak, M. Salim, D. A. Nikcevich, S. R. Dakhil, T. R. Fitch
Journal: Journal of Clinical Oncology (2006)

7574 Background: Patients (pts) with relapsed aggressive NHL are usually treated with intensive platinum-based chemotherapy regimens prior to stem cell transplant (SCT). This study was designed to learn the toxicity and efficacy of adding 4 doses of rituximab to the standard DHAP salvage chemotherapy regimen. Methods: Eligible pts had biopsy-proven relapsed CD20+ NHL and were eligible for platinum-based chemotherapy. Pts were treated with rituximab 375 mg/m 2 d1,8,15, and 22 as well as cis-platinum 100 mg/m 2 d3, cytosine arabinoside 2 g/m 2 IV q 12 hours x two doses d4, dexamethasone 40 mg PO/IV d3–6, and G-CSF d5–14. Pts were restaged after 1 and 2 cycles; responding pts could proceed to SCT or further cycles of DHAP at MD discretion. There was no provision for rituximab maintenance. The goal was to achieve an overall response rate (ORR) of ≥ 75%. Results: Fifty-eight pts were enrolled between 10/29/00 and 6/20/03. The median age was 63 years (range, 43–83). One pt was ineligible because the tumor was CD20-. All 57 eligible pts completed one cycle; 48 pts completed 2 cycles. The ORR was 70% (40/57) with 16 (28%) CR/CRu and 24 (42%) PR. For all 57 pts, the median TTP was 13.1 months (mos) (95% CI: 7.3–18.2) and the median OS 30.5 mos (95% CI: 17.8–52.5). Seventeen pts (30%) proceeded to SCT. The median duration of response (DR), time to progression (TTP) and overall survival (OS) for the SCT pts were 41.6, 42.3, and 43.6 mos, respectively. The median DR, TTP, and OS for the 25 pts who responded to RDHAP but did not proceed to SCT were 12.4, 13.1, and 38.8 mos, respectively. The incidence of grade 3 and 4 thrombocytopenia was 53% and 39%, respectively. The incidence of grade 3 and 4 neutropenia was 11% and 68%, respectively. Six pts (11%) had nephrotoxicity–five grade 3 and two grade 4 (one pt had both) and one pt required dialysis. Conclusions: The addition of rituximab to standard DHAP is safe with similar toxicity profile to DHAP alone. Despite a high ORR, the CR rate and the % pts proceeding to SCT in this cooperative group setting remain low. New agents are needed that can be added to these regimens to increase the effectiveness and reduce toxicity to allow more pts to proceed to SCT. No significant financial relationships to disclose.
Neutrophilic superoxide production can assess pharmacological and pharmacogenetic β‐adrenoreceptor effects
Authors: M. T. Reinartz, M. Wetzke, C. Happle, S. Kälble, R. Scherer, M. Kabesch, R. Seifert
Journal: Allergy (2016)

Asthma can be controlled well in most patients by inhaled β-adrenoreceptor (β2 AR) agonists and steroids. Poor response to β2 AR agonists is difficult to predict, especially in young children and by lung function testing, which may be affected by multiple influences. As an alternative approach, we analyzed ex vivo neutrophilic superoxide inhibition in response to β2 AR stimulation. In 60 healthy volunteers, this assay was unaffected by sex, age, smoking, atopy or asthma status. Furthermore, we assessed effects of genetic variants in β2 AR by sequencing the ADRB2 gene in our cohort and relating genotypes to β2 AR-mediated neutrophilic superoxide inhibition. Gly16Arg genotypes correlated with minor decrease in overall adrenoresponse in this small study population. Taken together, ex vivo testing of the β2 AR response in human neutrophils represents a robust tool with good signal-to-noise ratio at physiological β2 AR agonist concentrations, and this assay may be useful to complement future pharmacogenetic studies in asthma.
Lack of Evidence of an Association between Mitral-Valve Prolapse and Stroke in Young Patients
Authors: Dan Gilon, Ferdinando S. Buonanno, Marshall M. Joffe, Marcia Leavitt, Jane E. Marshall, J. Philip Kistler, Robert A. Levine
Journal: New England Journal of Medicine (1999)

Previous studies have reported a high prevalence of mitral-valve prolapse among patients with embolic stroke (28 to 40 percent), especially among young patients (those ≤45 years old); this finding has practical implications for prophylaxis. However, diagnostic criteria for prolapse have changed and are now based on three-dimensional analysis of the shape of the valve; use of the current criteria reduces markedly the frequency of such a diagnosis and increases its specificity. Previously described complications must therefore be reconsidered.
Hereditary Transmission of Exceptional Resistance to Coumarin Anticoagulant Drugs
Authors: Robert A. O'Reilly, Paul M. Aggeler, M. Silvija Hoag, Lois S. Leong, Mona L. Kropatkin
Journal: New England Journal of Medicine (1964)

THE variability of response of human beings to many drugs is usually continuous and gives a unimodal frequency-distribution curve for the drug action measured. These unimodal distribution curves are consistent with multifactorial inheritance and are difficult to analyze for the genetic influences involved. The few drugs that have a discontinuous variation in action show a bimodal or trimodal distribution. This probably indicates a single gene system with each mode representing a phenotype1 from which the genotype may be inferred. This multimodal distribution curve of drug response is usually the result of an alteration in drug metabolism and causes increased sensitivity . . .
Thyroid disorders in female psychiatric patients with panic disorder or agoraphobia
Authors: H Orenstein, A Peskind, M A Raskind
Journal: American Journal of Psychiatry (1988)

The authors interviewed 144 consecutive female psychiatric patients and found that those with a lifetime history of either panic disorder or agoraphobia with panic attacks (panic/agoraphobia) were more likely than other patients to report a history of hyperthyroidism or goiter in themselves and in their first-degree relatives. A personal history of hyperthyroidism or goiter was found almost exclusively in the subgroup of patients with panic/agoraphobia who also had a lifetime history of major depression.
The Rectal Administration of Aureomycin in Children
Authors: A. C. Siegel, G. H. Nickerson, C. D. Cook
Journal: New England Journal of Medicine (1952)

AUREOMYCIN, when given orally, particularly in infants and children, may be difficult to administer, and may occasionally produce nausea and vomiting. Children may be unable to take capsules, and attempts to disguise the bitter taste of the drug with flavoring have not been entirely successful in facilitating its use in the pediatric age group. Such substances as aspirin, barbiturates, glucose and water are effectively absorbed from the rectum; hence, it seemed possible that aureomycin might equally well be absorbed in this fashion. For these reasons, and because rectal administration of the antibiotic had already been adopted by many practitioners, the . . .
Hypertension, Neutropenia, Thrombocytopenia, Normal Sodium and Ldh Within the First 12 Weeks of Treatment As Independent Biomarkers of Outcome in Metastatic Renal Cell Carcinoma (Mrcc)
Authors: A.V. Soerensen, P.F. Geertsen, I.J. Christensen, G.G. Hermann, N.V. Jensen, K. Fode, A. Petersen, R. Sandin, F. Donskov
Journal: Annals of Oncology (2014)
Chemotherapy-induced transient CEA and CA19–9 surges in patients with metastatic or recurrent gastric cancer
Authors: K. Lee, H. Kim, Y. Kim, D. Oh, J. Kim, S. Im, T. Kim, J. Lee, Y. Bang
Journal: Journal of Clinical Oncology (2008)

15603 Background: A rising of carcinoembryonic antigen (CEA) or carbohydrate antigen 19–9 (CA19–9) after chemotherapy is generally considered as tumor progression in patients with solid tumors. However, a transient elevation of CEA has been observed despite objective responses in metastatic colorectal or breast cancer patients receiving chemotherapy. This transient CEA surge phenomenon has not been previously described in patients with metastatic or recurrent gastric cancer (MRGC) and CA19–9 surge phenomenon has never been reported in solid tumor patients. Thus this study was performed to investigate the incidence of CEA and CA19–9 surges in MRGC patients and their implications on clinical outcome. Methods: Among 177 MRGC patients who received palliative chemotherapy at Seoul National University Bundang Hospital from January 2005 to July 2007, 51 and 40 patients had evaluable data for CEA or CA19–9 surges, respectively, and thus were included in this study. Both CEA and CA 19–9 surges were defined as a > 20% increase in these tumor markers from baseline (within 2 weeks from initial treatment) that is followed by a >20% drop in subsequent tumor marker levels compared to baseline. Results: Of 51 patients who were evaluable for CEA surges, 9 patients (17.6%) had documented CEA surges. The median time to CEA peak and the median duration of CEA surge were 2.8 weeks (range: 1.7∼7.0 weeks) and 9.1 weeks (range: 7.6∼21.0 weeks), respectively. Of 40 evaluable patients for CA19–9 surge, 7 patients (17.5%) had documented CA19–9 surge. The median time to CA19–9 peak and the median duration of CA19–9 surge were 2.3 weeks (range: 1.9∼6.0 weeks) and 7.1 weeks (range: 4.3∼16.1 weeks). All patients with CEA or CA19–9 surges had radiographic evidence of benefit (radiological response or stable disease) from chemotherapy. Conclusions: CEA or CA19–9 surges can be observed in MRGC patients receiving chemotherapy. All patients with these surge phenomenons had clinical benefits from chemotherapy. An initial rise in CEA or CA19–9 levels after initiation of chemotherapy should not be used as an indicator of progressive disease. No significant financial relationships to disclose.
Endomitotic Reduplication Mechanisms in Ascites Tumors of the Mouse&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: A LEVAN, T S HAUSCHKA
Journal: JNCI Journal of the National Cancer Institute (1953)

Journal Article Endomitotic Reduplication Mechanisms in Ascites Tumors of the Mouse Get access Albert Levan, Albert Levan Search for other works by this author on: Oxford Academic PubMed Google Scholar Theodore S. Hauschka Theodore S. Hauschka Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 14, Issue 1, August 1953, Pages 1–43, https://doi.org/10.1093/jnci/14.1.1 Published: 01 August 1953 Article history Received: 06 February 1953 Published: 01 August 1953
Analysis of the p53 pathway in clear cell renal cell carcinoma to identify novel drug combinations.
Authors: Mark T. Boyd, Amro Ahmed-Ebbiary, Radoslaw Polanski, Aidan Noon, Keith Parsons, Carlos P. Rubbi, Nikolina Vlatkovic
Journal: Journal of Clinical Oncology (2012)

460 Background: p53 is rarely mutated in clear cell renal cell carcinoma (ccRCC) with typical mutation frequencies between 0 and 5%. Recent studies have shown that combined p53/MDM2 expression is significantly linked with reduced survival (P&lt;0.0001, HR=3.2) and is an independent prognostic indicator (Cox multiple regression analysis, P=0.027). Studies have also found that p53 is negatively regulated by MDM2 in RCC cells but that rescue of p53 stability is not effective at inducing apoptosis. Studies of normal kidney have shown that signalling to p53 by genotoxic agents is intact, but fail to elicit an apoptotic response. We have therefore investigated a rational combinatorial approach to drug targeting in RCC cells in which both MDM2 is inhibited and apoptosis is stimulated. Methods: Senescence was quantitated by assaying SA-β-galactosidase. Drug sensitivity was determined by measuring MTT conversion at multiple time points. Data from these were used to generate isobolograms and combination indices. Further details of the drugs used will be presented. Results: Using a p53-MDM2 antagonist (currently in clinical trials), our results indicate that in RCC cells rescue of p53 induces some growth arrest and senescence but not apoptosis (IC70 range 7-30 μM). Similarly, using a pro-apoptotic drug (also in clinical trials) which has been demonstrated to promote apoptosis in a wide range of cells, we find little growth inhibitory effect (IC70 range 2.5-30 μM). However, combining a p53-MDM2 antagonist with the pro-apoptotic drug leads to dramatic synergy (combination indices as low as 0.26 [&lt;1 indicates synergy]) and rapid p53-dependent apoptosis in a range of p53 wild-type RCC cell lines. Crucially, the drug combinations have no impact on non-tumour renal cells (neither IC70 nor IC50 could be determined, but both exceed 30 μM) suggesting these may have a high therapeutic index. Conclusions: Rationally designed combinatorial approaches for the treatment of RCC can lead to dramatic enhancement of RCC cell sensitivity and clearly warrant further investigation in both pre-clinical studies (under development) and in clinical trials for RCC due to the retention of wild-type p53 in this disease.
Acceptable safety of bevacizumab therapy in patients with brain metastases due to non-small cell lung cancer
Authors: W. L. Akerley, C. J. Langer, Y. Oh, D. K. Strickland, S. Joo Royer, Q. Xia, Y. Mu, J. Huang, M. A. Socinski
Journal: Journal of Clinical Oncology (2008)

8043 Background: Bevacizumab (Bv) + carboplatin/paclitaxel received FDA approval in 10/06 for improving survival in first-line treatment of advanced NSCLC patients (pts) without brain metastases (mets). We report on the safety of Bv therapy in combination with standard therapy in 91 pts with NSCLC and treated (tx) brain mets. Methods: Subjects were treated on protocols ATLAS or PASSPORT. The ATLAS phase III study allows chemo+ Bv, followed by Bv ± erlotinib (E) to disease progression, for pts with advanced non-squamous or peripherally located squamous NSCLC. Tx for brain mets was whole brain radiotherapy (WBRT). The PASSPORT phase II study tests Bv in combination with first or second line systemic therapy in subjects with non- squamous NSCLC and tx brain mets. Treatment for brain mets includes radiosurgery (RS), neurosurgery (NS) or WBRT. The overall rate of central nervous system (CNS) hemorrhage and exact 95% CI using Blyth-Still-Casella methodology are reported. Results: Data collected: March 2006 through October 2007. The median number of Bv doses (15 mg/kg/q3w) in 85 Bv tx pts was 4 (range 1–17); 6 pts were non-Bv treated. No CNS hemorrhages were reported on either study during the main study tx (95 % CI: 0, 4.2). One Grade 2 CNS bleed was observed in a pt on post-progression therapy in ATLAS after 14 cycles of Bv; pt’s site of disease progression was CNS mets. In Bv tx pts, seven had Grade (Gr) 3–5 CNS events: one had Gr 5 cerebral arterioscelerosis and Gr 3 leukoencephalopathy, one had Gr 3 ataxia, one had Gr 3 convulsion, three had Gr 3 mental status change, and one had Gr 3 syncope. Conclusions: 85 subjects with treated brain metastases have received bevacizumab without symptomatic Gr≥2 hemorrhages observed during the main treatment (pre-progression) phase; no additional safety signals were identified. These data strongly suggest the safety of bevacizumab in advanced NSCLC pts with treated brain mets. ATLAS PASSPORT N Total: 26 Total: 65 Men: 17 Men: 37 Women: 9 Women: 28 Median Age 61 60 Prior Therapy for CNS Mets WBRT: 242 patients were enrolled with untreated brain mets WBRT alone: 35 WBRT + RS/NS: 12 NS alone: 1 RS alone: 15 TBD: 2 Treatment Line 1st Line: 26 1st Line: 38 2nd Line: 26 TBD: 1 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology Genentech™ BioOncology
Single Oblique-View Mammography for Periodic Screening for Breast Cancer in Women&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: B Lundgren, A Helleberg
Journal: JNCI Journal of the National Cancer Institute (1982)

A population, originally 6,845 women, 40 years of age and over, was screened for breast cancer by single oblique-view mammography in 1974, 1977, and 1980. Of the 5,789 women remaining in their parish in 1980, 94% had attended the screening at least once. Of 111 breast cancers diagnosed in the 6.25-year study period, 78% were detected at screening, 15% as interval cancers, and 7% among nonresponders. Sixty-three percent of the women had tumors in clinical stage I, and 59% had tumors less than or equal to 10 mm. The predictive value for biopsy recommendations by mammography was 79%. This method was considered very suitable for screening. In the older age groups there was probably some overdiagnosis of cancers that would never have become symptomatic.
Metabolic Adjustments to Normal and Disturbed Circulation in Man
Authors: Elliot V. Newman
Journal: New England Journal of Medicine (1954)

IN the performance of usual physical activity, the normal circulatory apparatus is called upon to supply varying amounts of blood to tissues. It has been well demonstrated that the normal circulation does not respond with enough rapidity or quantity of blood to maintain the metabolic condition of the tissues in a compensated or "steady" state. The normal man who rises from his bed to walk makes metabolic as well as circulatory adjustments in response to the activity. Until the output of the heart and the delivery of blood to the working tissues catch up with the demands, the tissues themselves . . .
Association of Wilms's Tumor with Aniridia, Hemihypertrophy and Other Congenital Malformations
Authors: Robert W. Miller, Joseph F. Fraumeni, Miriam D. Manning
Journal: New England Journal of Medicine (1964)

WHEN, through epidemiologic study of persons or families, diseases are found to be associated, the opportunities for determining their etiology may be very much increased. The association of leukemia and mongolism1 is an example. An accumulation of case reports in the past decade suggests a link between another childhood cancer, Wilms's tumor, and a rare congenital defect, total hemihypertrophy.2 3 4 5 6 7 8 In addition, isolated cases of Wilms's tumor in horseshoe kidneys have been reported.9 The purpose of this presentation is to define more fully the relation between Wilms's tumor and congenital defects by study of the diagnoses contained in the medical records . . .
Pathology of a Lower Esophageal Ring
Authors: H. Edward MacMahon, Richard Schatzki, John E. Gary
Journal: New England Journal of Medicine (1958)

TEMPLETON,1 in 1944, in discussing the x-ray appearance of the lower esophagus, described as a curiosity of doubtful significance a narrow, ringlike constriction, seen only in the distended state of the esophagus, a few centimeters above the diaphragmatic shadow. This annular ring always remained in the same location. He was unaware of the cause, but he emphasized the importance of recognizing and of distinguishing it from any type of organic structure. Similar roentgenologic observations were made by Jutras, Levrier and Longtin,2 Johnstone3 and Evans,4 and several suggestions were offered to explain it. One of these, offered by Jutras and his . . .