tbuckley/cabot-search huggingface dataset:
Cisplatin and Oxaliplatin Toxicity: Importance of Cochlear Kinetics as a Determinant for Ototoxicity
Authors: V. Hellberg, I. Wallin, S. Eriksson, E. Hernlund, E. Jerremalm, M. Berndtsson, S. Eksborg, E. S. J. Arner, M. Shoshan, H. Ehrsson, G. Laurell
Journal: JNCI Journal of the National Cancer Institute (2008)

Cisplatin is a cornerstone anticancer drug with pronounced ototoxicity, whereas oxaliplatin, a platinum derivative with a different clinical profile, is rarely ototoxic. This difference has not been explained. In HCT116 cells, cisplatin (20 μM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold), to 3.1-fold induction (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging from 9.3-fold (95% CI = 8.8- to 9.8-fold), to 5.1-fold (95% CI = 4.4- to 5.8-fold). A guinea pig model (n = 23) was used to examine pharmacokinetics. Drug concentrations were determined by liquid chromatography with post-column derivatization. The total platinum concentration in cochlear tissue was determined by inductively coupled plasma mass spectrometry. Drug pharmacokinetics was assessed by determining the area under the concentration–time curve (AUC). Statistical tests were two-sided. In HCT116 cells, cisplatin (20 μM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold to 3.1-fold induction) (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging (from 9.3-fold, 95% CI = 8.8- to 9.8-fold, to 5.1-fold, 95% CI = 4.4- to 5.8-fold). Oxaliplatin (20 μM)-induced apoptosis was unaffected by calcium chelation (from 7.1- to 6.2-fold induction) and by superoxide scavenging (from 5.9- to 5.6-fold induction). In guinea pig cochlea, total platinum concentration (0.12 vs 0.63 μg/kg, respectively, P = .008) and perilymphatic drug concentrations (238 vs 515 μM × minute, respectively, P < .001) were lower after intravenous oxaliplatin treatment (16.6 mg/kg) than after equimolar cisplatin treatment (12.5 mg/kg). However, after a non-ototoxic cisplatin dose (5 mg/kg) or the same oxaliplatin dose (16.6 mg/kg), the AUC for perilymphatic concentrations was similar, indicating that the two drugs have different cochlear pharmacokinetics. Cisplatin- but not oxaliplatin-induced apoptosis involved superoxide-related pathways. Lower cochlear uptake of oxaliplatin than cisplatin appears to be a major explanation for its lower ototoxicity.
Active morbidity surveillance after Hurricane Andrew--Florida, 1992
Authors: L. E. Lee
Journal: JAMA (1993)

To describe the health status of and to detect disease outbreaks in the population affected by Hurricane Andrew in south Dade County, Florida.The Florida Department of Health and Rehabilitative Services and the US Army conducted active surveillance for gastrointestinal illness, respiratory illness, injury, and other index conditions by monitoring civilian and service member visits to care sites (civilian and military free care sites and hospital emergency departments) from August 30 (1 week after the hurricane's landfall) through September 30, 1992.South Dade County, Florida.Proportional morbidity: the number of daily visits for each index condition divided by the total number of visits, expressed as a percentage. Morbidity rate: the total number of daily visits by service members divided by the total number of service members, expressed as a percentage.Six index conditions accounted for 41.3% of visits to civilian free care sites: diarrhea (4.7%), cough (4.7%), other infection (9.6%), rash (5.4%), animal bite (1.2%), and injury (15.7%). At military free care sites, five index conditions accounted for 75.7% of civilian visits: injury (23.7%), dermatologic illness (12.4%), respiratory illness (9.9%), gastrointestinal illness (5.3%), and other medical conditions (24.4%). Two index conditions accounted for 54.1% of service member visits: injury (36.2%) and dermatologic illness (17.9%). During the 5 weeks after the hurricane, proportional morbidity from injury decreased; proportional morbidity from respiratory illness increased; and proportional morbidity from diarrhea was stable. No infectious disease outbreaks occurred.Injuries were an important source of morbidity throughout the surveillance period, especially among service members. Enteric and respiratory agents did not cause disease outbreaks, despite alarming rumors to the contrary.
Relation between Cancer and Congenital Defects in Man
Authors: Robert W. Miller
Journal: New England Journal of Medicine (1966)

WHEN diseases are found to occur together more often than can be attributed to chance, each can be studied in the light of what is known of the other for clues to etiology. Particularly informative in this regard has been a series of recent observations linking certain cancers with specific malformations. Presented here is a perspective of current knowledge concerning the excessive coexistence of these diseases as determined by study of individuals, families or communities.Concurrence of Cancer and Congenital Defects in IndividualsCancer and Down's SyndromePediatricians generally knew from clinical experience that in children with Down's syndrome (mongolism) . . .
Radon Risk Assessed
Authors: Charles Marwick
Journal: JAMA (1988)

IN A NEW analysis of the possibility of developing lung cancer following exposure to radon, the National Research Council's Committee on the Biological Effects of Ionizing Radiation revises the risk downward from that in a report it issued eight years ago. Radon is an odorless and colorless gas formed by the radioactive decay of uranium in soil (<i>JAMA</i>1987;258:578-579). It is regarded as a major pollutant because many of today's houses are tightly sealed against the weather and the gas tends to build up inside them. The latest analysis concludes that lifetime exposure to radon for what is termed one<i>working-level month</i>increases an individual's chances of dying from lung cancer by 1½ times compared with someone who is exposed only to background levels of radon. For every 1 million people exposed over a lifetime to one working-level month of radon, there would be about 350 more deaths from lung
Cigarette smoking and breast cancer
Authors: K. Bennicke, C. Conrad, S. Sabroe, H. T. Sorensen
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To investigate cigarette smoking in relation to the risk of breast cancer. <b>Design</b>: Interviews with women referred for mammography. <b>Setting</b>: Hjorring District Hospital, a public, population based hospital in Denmark. <b>Subjects</b>: 3240 women aged 15-92 years referred for mammography during 1 June 1989 to 1 November 1991. <b>Main outcome measures</b>: Smoking, parity, age, reason for referral, breast cancer. <b>Results</b>: In a multiple logistic regression analysis adjusted for six variables a pronounced increased risk of breast cancer was found in women who had smoked for over 20 years, and this was significant in women who had smoked for over 30 years (odds ratio 1.6, 95% confidence interval 1.1 to 2.3). The median age of women with breast cancer was 59 (range 31-81) years for smokers and 67 (38–92) years for nonsmokers. The difference of eight years between the median ages was significant (P&lt;0.01). <b>Conclusion</b>: Smoking may increase the risk of breast cancer after 30 years of smoking. <h3>Key messages</h3> Key messages It has been suggested that smoking protects against breast cancer because of an antioestrogenic effect This study shows, however, that women who have smoked for more than 30 years have an increased risk of developing breast cancer Moreover, smokers with breast cancer were eight years younger than non-smokers with breast cancer
Angiotensin Selectively Activates a Subpopulation of Postganglionic Sympathetic Neurons in Mice
Authors: Xiuying Ma, Mark W. Chapleau, Carol A. Whiteis, Francois M. Abboud, Klaus Bielefeldt
Journal: Circulation Research (2001)

Abstract —Angiotensin II (Ang II) increases renal sympathetic nerve activity in anesthetized mice before and after ganglionic blockade, suggesting that Ang II may directly activate postganglionic sympathetic neurons. The present study directly tested this hypothesis in vitro. Neurons were dissociated from aortic-renal and celiac ganglia of C57BL/6J mice. Cytosolic Ca 2+ concentration ([Ca 2+ ] i ) was measured with ratio imaging using fura 2. Ang II increased [Ca 2+ ] i in a subpopulation of sympathetic neurons. At a concentration of 200 nmol/L, 14 (67%) of 21 neurons responded with a rise in [Ca 2+ ] i . The Ang II type 1 (AT 1 ) receptor blocker (losartan, 2 μmol/L) but not the Ang II type 2 (AT 2 ) receptor blocker (PD123,319, 4 μmol/L) blocked this effect. The Ang II–induced [Ca 2+ ] i increase was abolished by removal of extracellular Ca 2+ but not altered by depletion of intracellular Ca 2+ stores with thapsigargin. Ang II no longer elicited a [Ca 2+ ] i increase in the presence of lanthanum (25 μmol/L). The specific N-type and L-type Ca 2+ channel blockers, ω-conotoxin GVIA and nifedipine, respectively, significantly inhibited the Ang II–induced [Ca 2+ ] i increase. The protein kinase C inhibitor H7 but not the protein kinase A inhibitor H89 blocked the response to Ang II. These results demonstrate that Ang II selectively activates a subpopulation of postganglionic sympathetic neurons in aortic-renal and celiac ganglia, triggering Ca 2+ influx through voltage-gated Ca 2+ channels. This effect is mediated through AT 1 receptors and requires the activation of protein kinase C. The activation of a subgroup of sympathetic neurons by Ang II may exert unique effects on kidney function in pathological states associated with elevated Ang II.
Quiet diplomacy is not enough
Authors: Paul Haviland
Journal: BMJ (2004)

Here is a familiar story: a lethal infection is discovered to have spread among hospital patients. The culprits are quickly identified as substandard hygiene and poor training. On a more sinister note, there is a suspicion in some quarters that foreign staff, already present in large numbers in the country's health service, are somehow to blame.

So far, so familiar: just weeks ago parts of the British media were treating the “superbug” crisis in precisely those terms.

Now imagine that a handful of foreign hospital workers are rounded up, imprisoned, and charged with deliberately spreading the infection, a charge to which they confess under torture. After five and a half years in judicial limbo, they are found guilty and sentenced to death by firing squad. Friends and relatives of those who died pour on to the streets to welcome the verdicts with whoops of joy.

> Those who should be putting pressure on Libya are acting with exaggerated caution 

Implausible? Think again. On 6 May this year, in the Libyan …
Successful outcome of pregnancy in patients with anti-neutrophil cytoplasm antibody–associated small vessel vasculitis
Authors: Adam P. Croft, Stuart W. Smith, Sue Carr, Sajeda Youssouf, Alan D. Salama, Aine Burns, Charles D. Pusey, Patrick Hamilton, Nina Brown, Michael Venning, Lorraine Harper, Matthew D. Morgan
Journal: Kidney International (2014)

Pregnancy in patients with anti-neutrophil cytoplasm antibody-associated vasculitis is reportedly associated with a high risk of fetal and maternal complications. Here we describe the outcome of pregnancies in patients with granulomatosis with polyangiitis and microscopic polyangiitis at five centers in the United Kingdom using a retrospective case review of all women who became pregnant following diagnosis. We report 15 pregnancies in 13 women resulting in 15 live births including one twin pregnancy and 13 singleton pregnancies. One patient had an unplanned pregnancy and a first trimester miscarriage while taking methotrexate. All other pregnancies were planned following a minimum of 6 months clinical remission. Eleven successful pregnancies were delivered vaginally at full term, whereas three were delivered by cesarean section. All infants were healthy with no neonatal complications on their initial health check within the first 24 h of delivery and no evidence of neonatal vasculitis. One relapse occurred during pregnancy and was successfully treated with an increased dose of azathioprine and corticosteroids, intravenous immunoglobulin, and plasma exchange therapy. One patient developed tracheal crusting and subglottic stenosis of infective etiology in the third trimester requiring tracheal debridement post delivery. No patient had a relapse in the first 12 months postpartum. Thus, successful pregnancy outcomes can occur following planned pregnancy in women in sustained remission on non-teratogenic therapies.
Acts of judgment, not epistemic triangles
Authors: Leslie Smith
Journal: Behavioral and Brain Sciences (2004)

Carpendale &amp; Lewis's (C&amp;L's) reanalysis of Chapman's (1999) epistemic triangle dealing with the coordination of interactions with physical objects and people's communication is misleadingly incomplete. An alternative proposal is outlined combining the causality of action with the normativity of knowledge in acts of judgment. This alternative is empirical and developmental, with a focus on rich but neglected phenomena.
Cutaneous Porphyria in Turkey
Authors: Rudi Schmid
Journal: New England Journal of Medicine (1960)

SCATTERED reports of an outbreak of cutaneous porphyria in Turkey have been received recently. In the course of a short visit to that country in January, 1960, an attempt was made to gather all available information and to supplement it with some personal observations and investigations.Since the summer of 1956 a great number of cases of cutaneous porphyria have appeared in the Turkish provinces of Diyarbakir, Mardin and Urfa. A few isolated cases had already been observed in Urfa in 1955, but before that date, porphyria had not been noted in Turkey. The syndrome consists of blistering and epidermolysis . . .
Abstract 3500: T cells redirected against HER2 for the adoptive immunotherapy for HER2-positive osteosarcoma
Authors: Nabil Ahmed, Vita Brawley, Oumar Diouf, Peter Anderson, John Hicks, Lisa Wang, Gianpietro Dotti, Winfried Wels, Hao Liu, Adrian Gee, Cliona Rooney, Malcolm Brenner, Helen Heslop, Stephen Gottschalk
Journal: Cancer Research (2012)

Abstract INTRODUCTION: The prognosis for patients with advanced osteosarcoma (OS) has not improved over the last two decades. Hence novel biologically-based therapies, such as immunotherapy, are needed for these patients. We have shown in preclinical studies that T cells, genetically modified with a HER2-specific chimeric antigen receptor (CAR; HER2-CAR T cells), kill HER2+ OS cells ex vivo and induce regression of HER2+ OS xenografts in animal models. Based on these findings we developed a Phase I/II clinical study with HER2-CAR T cells in patients with metastatic and/or recurrent OS. METHODS: The primary objective of this clinical trial is to determine the safety of escalating doses of HER2-CAR T cells in patients with advanced HER2+ OS. The secondary objective is to determine the expansion, persistence and anti-tumor effects of infused HER2-CAR T cells. RESULTS: 43 (78%) out of 55 screened OS patients had HER2+ tumors. Twenty one HER2-CAR T-cell lines have been generated to date by retroviral transduction. Median HER2-CAR expression was 67.4% (range 50.7-85.6%) and HER2-CAR T cells killed HER2+ OS cells in contrast to non-transduced T cells (p &amp;lt;0.0001). The median CD4+:CD8+ T-cell ratio was 1:1.3, and T-cell products contained naïve (CD45RA+; median: 11.8%; range 2.4-33.2%), effector memory (CD45RO+/CCR7-/CD62L-; median: 29.3%; range: 7.8-67.5%), and central memory T cells (CD45RO+/CD62L+; median 55.9%; range: 21.9-87.9%). Nine patients have been infused so far at HER2-CAR T-cell doses between 104/m2 to 1x106/m2. Infusions were well tolerated without systemic side effects, and no increase of proinflammatory cytokines (IL-2, IFN-γ, GM-CSF, TNF-α) was observed in the patients’ plasma post infusion. HER2-CAR T cells were detectable for up to 3 months post infusion. CONCLUSION: HER2-CAR T cells have shown promising antitumor activity in preclinical OS animal models. We are currently evaluating the safety and efficacy of HER2-CAR T cells in a Phase I/II clinical study. Initial safety data at low T-cell dose levels are encouraging, warranting further active exploration of HER2-CAR T-cell based therapies for OS and other HER2+ malignancies. 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 3500. doi:1538-7445.AM2012-3500
Work-exacerbated asthma and occupational asthma: Do they really differ?
Authors: Catherine Lemière, Louis-Phillippe Boulet, Simone Chaboillez, Amélie Forget, Samah Chiry, Hélène Villeneuve, Philippe Prince, Karim Maghni, Wendy A. Kennedy, Lucie Blais
Journal: Journal of Allergy and Clinical Immunology (2012)
Snake Poisoning—A Case of Plagiarism
Authors: B. H. Orndorff
Journal: JAMA (1910)

The article is a publication of abstracts taken from several original articles appearing in current literature. These abstracts I prepared to assist me in giving a lecture on the subject and were intended to be the basis of an article for publication; however the abstracts, as they stood, appeared in the Medical Standard without my seeing a proof sheet for approval, indeed, the first portion appeared while I was in Europe, the second about fifteen days after my return.  All credit to the men writing the original articles was unfortunately omitted and the publication, as it stands, appears as a clumsy combination of plagiarism and ignorance on the part of the author. While I am certain there is nothing I can say or do that will amend the injustice inflicted on the men whose brains have developed the material from which these abstracts were taken, still it would please me
Sickle cell problems continue to challenge medical science, but some progress is noted
Authors: C. Marwick
Journal: JAMA (1990)

NEARLY THREE DECADES ago, an automobile accident victim was brought to Johns Hopkins Hospital's emergency department in Baltimore, Md. At the time, in an attempt to determine the frequency of the sickle cell gene in the population, all admissions to the hospital were being tested for it. The trauma victim, a woman, turned out to have primarily sickle cell hemoglobin in her blood, but otherwise was completely asymptomatic. Further investigation revealed that the woman had both sickle cell trait and a rare disorder—hereditary persistence of fetal hemoglobin. Almost one third of her total hemoglobin was made up of this form, the remainder being sickle hemoglobin—hemoglobin S (<i>Bull Johns Hopkins Hosp.</i>1961;108:242-257). Most persons have about 1% fetal hemoglobin, while typical patients with sickle cell anemia have fetal hemoglobin levels of between 2% and 7%. <h3>Fetal Hemoglobin's Significance</h3> Since the patient was asymptomatic, says Samuel Charache, MD, professor of medicine at
Lysine and protein metabolism in young women. Subdivision based on the novel use of multiple stable isotopic labels.
Authors: C S Irving, M R Thomas, E W Malphus, L Marks, W W Wong, T W Boutton, P D Klein
Journal: Journal of Clinical Investigation (1986)

A multitracer stable isotope study of lysine kinetics was carried out in fasted adult female volunteers to determine whether a multicompartmental model that partitions protein synthesis and breakdown into at least two types of tissue components can be constructed from plasma and breath data. Five female subjects, maintained on formula diets, received L-[13C1]lysine (27 mumol/kg) as an i.v. bolus and L-[15N2]lysine (27 mumol/kg) as an oral bolus 4 h postprandially. Plasma and breath samples were collected for 6 h. On an alternate day, subjects received NaH13CO3 (10 mumol/kg) as an i.v. bolus and breath samples were collected for 6 h. Plasma tracer lysine levels were determined by gas chromatography-mass spectrometry isotope ratiometry, and breath 13CO2 levels were measured by mass spectrometric gas isotope ratiometry. The tracer data could be fitted to a mammillary multicompartmental model that consisted of a lysine central compartment and slow- and fast-exchanging peripheral compartments containing 37, 38, and 324 mumol/kg, respectively. The rates of lysine oxidation, incorporation into protein, and release by protein breakdown were 21, 35, and 56 mmol/kg/h, respectively, in the fast-exchanging compartment, whereas the rates of protein synthesis and breakdown in the slow compartment were both 53 mmol/kg/min. These values corresponded to a whole-body lysine flux of 106 mmol/kg/h. The kinetic parameters were in excellent agreement with reported values obtained by constant-infusion methods. The measurements indicated that it will be possible to detect changes in amino acid pool sizes and protein synthesis and breakdown associated with the mobilization of protein stores from plasma and breath measurements in multitracer stable isotope experiments.
Cancer is main cause of death in Britain
Authors: S. Mayor
Journal: BMJ (1998)

Cancer has now overtaken heart disease as the leading cause of death in Britain.

Figures released last week by the Cancer Research Campaign show that 156890 people in the United Kingdom died of cancer in 1996, compared with 148186 who died of coronary heart disease. This is a reversal of previous trends; heart disease has been the leading cause of death for many years. In 1992 it …
65 A THERAPEUTIC VACCINE FOR HCV BASED ON NOVEL, RARE, ADENOVIRAL VECTORS
Authors: C. Kelly, A. Folgori, S. Capone, E. Stafford, D. O'Donnell, K. Gantlett, J. Collier, A.C. Brown, R. Huddart, I. Humphreys, A. Kurioka, R. Townsend, L. Swadling, V. Ammendola, S. Colloca, M. Naddeo, L. Siani, C. Traboni, R. Córtese, A. Nicosia, P. Klenerman, E. Barnes
Journal: Journal of Hepatology (2011)