tbuckley/cabot-search huggingface dataset:
May We Not Secure Immunity from Fatal Chloroform Narcosis?
Authors: H. W. Dudley
Journal: JAMA (1903)

Indianapolis, March 19, 1903. <h3>To the Editor:</h3> —Chloroform, pleasant to take, quickly producing thorough muscular relaxation and complete insensibility to pain, would be the ideal anesthetic were it not for the dangers attending its use. These dangers arise so quickly that the system is overwhelmed before the anesthetist realizes that death is impending. Fatalities occur, not necessarily when large amounts of chloroform are used, but when gasps and deep inspirations fill the innermost alveoli with the concentrated vapor. Various apparatuses have been devised to properly dilute the vapor, but none has been altogether satisfactory. Parturient and pregnant women seldom, if ever, succumb to chloroform narcosis, for the following reasons: 1. In the parturient the central nervous system is in a state of congestion. 2. In both the pregnant and the parturient movement of the diaphragm is greatly restricted because of abdominal distension; therefore, breathing is necessarily shallow. As a consequence,
Simultaneous Multisite Mapping Studies During Induced Atrial Fibrillation in the Sterile Pericarditis Model
Authors: Koichiro Kumagai, Celeen Khrestian, Albert L. Waldo
Journal: Circulation (1997)

Chronic atrial fibrillation (AF) is thought to be due to multiple, simultaneously circulating wavelets. In the canine sterile pericarditis model, the mechanisms of maintenance of AF are not yet understood.During six induced AF episodes in six dogs with sterile pericarditis, 372 unipolar electrograms were recorded simultaneously from an electrode array placed around both atrial free walls, along with 10 to 24 electrodes from the atrial septum, by use of a multiplexing system. Activation maps during 12 consecutive 100-ms windows were analyzed from an episode of sustained AF in each dog (mean duration, 32 +/- 24 minutes). In two dogs, two such activation maps during the same episode of AF were analyzed. During AF, multiple unstable reentrant circuits (mean number, 1.4 +/- 0.1 per 100-ms analysis window) with very short cycle lengths (mean, 111 +/- 8 ms) present primarily in the atrial septum and right atrium were responsible for maintenance of AF. The unstable reentrant circuits frequently disappeared and re-formed. Wave fronts traveling from one atrium to the other and/or from the atrial septum play an important role in re-formation of unstable reentrant wave fronts.In this model of paroxysmal AF, unstable reentrant circuits of very short cycle length principally involving the atrial septum appear to be critical for maintenance of AF. Some reentrant circuits disappear as others re-form, so that at least one reentrant circuit is always present. Because the atria cannot follow their very short cycle lengths in a 1:1 manner, AF is maintained.
US halts University of Oklahoma clinical research
Authors: F. Charatan
Journal: BMJ (2000)

A new federal agency in the United States, established to protect the interests of patients who are the subjects of research, has shut down all government sponsored clinical trials at the University of Oklahoma Health Sciences Center at Tulsa, Oklahoma.

Michael Carome, chief compliance officer of the federal Office for Human Research Protections of the US Department of Health and Human Services, has been sharply critical of Dr Michael McGee, vice chairman of the department of surgery and principal researcher.

He also criticised the institutional review board of the university for failing to exercise meaningful oversight …
MEDICAL DICTION AND TERMINOLOGY
Authors: Ramsay Spillman
Journal: JAMA (1941)

<h3>To the Editor:—</h3> Twice today I have had telephone calls, from independent sources, stating that "a complete g-i examination" was desired. On cross examination—which should not be necessary but which I can testify is—it was revealed that an examination of only the stomach was desired. How much wasted effort and often expense would be saved if physicians could get together on terminology! To a roentgenologist g means gastro and i means intestinal, and any referring physician who gets on a high horse to my secretary when she tries to find out whether "a complete g-i examination" means a stomach and colon, a stomach and small intestine and colon or only a stomach is in a vulnerable position, as people always are who ride on high horses. If the terminology used by many physicians of my acquaintance reflects their schoolday teaching, the teaching has been sloppy. Another thing that annoys me
Ankylosing spondylitis, HLA-B27, and klebsiella: cross reactivity and antibody studies.
Authors: A Ebringer, M Ghuloom
Journal: Annals of the Rheumatic Diseases (1986)

Ankylosing spondylitis, HLA-B27, and klebsiella: cross reactivity and antibody studies SIR, The association of klebsiella with HLA-B27 involves two separate theoretical models which have been the subject of some debate, recently discussed by Singh et al,'
Induction of EBV–Latent Membrane Protein 1–Specific MHC Class II–Restricted T-Cell Responses against Natural Killer Lymphoma Cells
Authors: Hiroya Kobayashi, Toshihiro Nagato, Miki Takahara, Keisuke Sato, Shoji Kimura, Naoko Aoki, Makoto Azumi, Masatoshi Tateno, Yasuaki Harabuchi, Esteban Celis
Journal: Cancer Research (2008)

Abstract EBV-encoded latent membrane protein 1 (LMP1) has oncogenic potential and is expressed in many EBV-associated malignancies. Although LMP1 is regarded as a potential tumor-associated antigen for immunotherapy and several LMP1-specific MHC class I–restricted CTL epitopes have been reported, little is known regarding MHC class II–restricted CD4 helper T-lymphocyte (HTL) epitopes for LMP1. The goal of the present studies was to determine whether MHC class II–restricted CD4 T-cell responses could be induced against the LMP1 antigen and to evaluate the antitumor effect of these responses. We have combined the use of a predictive MHC class II binding peptide algorithm with in vitro vaccination of CD4 T cells using candidate peptides to identify naturally processed epitopes derived from LMP1 that elicit immune responses against EBV-expressing tumor cells. Peptide LMP1159-175 was effective in inducing HTL responses that were restricted by HLA-DR9, HLA-DR53, or HLA-DR15, indicating that this peptide behaves as a promiscuous T-cell epitope. Moreover, LMP1159-175–reactive HTL clones directly recognized EBV lymphoblastoid B cells, EBV-infected natural killer (NK)/T-lymphoma cells and naturally processed antigen in the form of LMP1+ tumor cell lysates presented by autologous dendritic cells. Because the newly identified epitope LMP1159-175 overlaps with an HLA-A2–restricted CTL epitope (LMP1159-167), this peptide might have the ability to induce simultaneous CTL and HTL responses against LMP1. Overall, our data should be relevant for the design and optimization of T-cell epitope–based immunotherapy against various EBV-associated malignancies, including NK/T cell lymphomas. [Cancer Res 2008;68(3):901–8]
Playing God: The New World of Medical Choices
Authors: John M. Clark
Journal: JAMA (1988)

A sudden automobile accident renders you comatose—what are your instructions for your own medical care? Has someone been appointed to act as your personal advocate to protect your interests? These are two of the provocative questions one considers while reading<i>Playing God: The New World of Medical Choices</i>. The authors, Thomas Scully, MD, professor of pediatrics and former dean of the University of Nevada School of Medicine, and his wife Celia Scully, a free-lance writer who has published more than 100 articles, elucidate important moral issues that we face as we become involved in the world of high-technology medicine. They write, "Nearly all the ethical debates surrounding medicine today—the right to die, whether to save a severely deformed infant, whether to give a dying patient an artificial heart—arise from technological advances." The reader is encouraged to find balanced information, become more assertive, and not be intimidated by the health care
Increased gallstone risk in humans conferred by common variant of hepatic ATP-binding cassette transporter for cholesterol
Authors: Frank Grünhage, Monica Acalovschi, Simona Tirziu, Maja Walier, Thomas F. Wienker, Anca Ciocan, Ofelia Mosteanu, Tilman Sauerbruch, Frank Lammert
Journal: Hepatology (2007)

Genomewide scans of inbred strains of mice have linked the genes encoding the hepatocanalicular cholesterol transporter ABCG5/G8 to gallstone formation. Five nonsynonymous coding single-nucleotide polymorphisms (SNPs) in the orthologous human genes are associated with differences in serum cholesterol and plant sterol levels. We now tested these ABCG5/G8 SNPs for linkage and association with gallstone susceptibility in humans. Prospectively, we collected data from 178 white individuals with gallbladder stones or history of cholecystectomy in 84 families and from 70 stone-free controls, as confirmed by abdominal ultrasound. We performed nonparametric linkage (NPL) analysis of affected sib pairs (ASPs) and association tests of cases and controls. In ASPs, gallstones were strongly linked to the D19H variant of the ABCG8 gene (NPL score = 7.1; P = 4.6 × 10−13). The risk of gallstones in carriers of the 19H allele was significantly increased in randomly selected cases from the ASP cohort compared to the stone-free controls (OR = 3.018; P = 0.017). Consistent with the mouse model, heterozygosity for the lithogenic ABCG8 allele was associated with gallstones in humans; 21.4% of gallstone patients carried the heterozygous D19H genotype, compared with 8.6% of controls (OR = 2.954; P = 0.026). Conclusion: The linkage and association studies identified the cholesterol transporter ABCG5/G8 as a genetic determinant of gallstone formation, or LITH gene, in humans. The function of this transporter and the results of the genetic study taken together indicate that in gallstone-susceptible carriers of the ABCG8 19H allele, cholesterol cholelithiasis is secondary to increased hepatobiliary cholesterol secretion. (Hepatology 2007.)
Psychiatric morbidity and physical toxicity associated with adjuvant chemotherapy
Authors: P. Maguire
Journal: BMJ (1980)

Our findings support the contention of Dr Walker and his colleagues that transplant rejection can be a cause of intrarenal aneurysms, and we believe that such aneurysms represent one extreme of the wide spectrum of arterio- pathic changes that can be demonstrated by arteriography during transplant rejection.5
Endothelial ICAM-1 Expression Associated With Inflammatory Cell Response in Human Ischemic Stroke
Authors: Perttu J. Lindsberg, Olli Carpe´n, Anders Paetau, Marja-Liisa Karjalainen-Lindsberg, Markku Kaste
Journal: Circulation (1996)

Background After focal brain ischemia, leukocytes adhere to the perturbed endothelium and are believed to aggravate reperfusion injury. Although ischemia-induced upregulation of endothelial adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and P-selectin, has been observed in experimental animals, the mechanism of cerebral leukocyte infiltration and thus therapeutic possibilities to reduce it in humans are uncertain. Methods and Results We counted the granulocytes, mononuclear phagocytes, and the percentages of cerebral microvessels expressing ICAM-1 by applying immunohistochemistry on brain sections showing a variable degree of neuronal damage from 11 human subjects who died 15 hours to 18 days after ischemic stroke and from normal control brains. In infarcted regions, granulocytes were detected as early as at 15 hours after injury (11.3 versus 0.5 cells/mm 2 in noninfarcted hemisphere); their amount exceeded 200 cells/mm 2 by 2.2 days but was back to normal level at 6.3 and 8.5 days. Acute infarctions (0.6 to 8.5 days) harbored significantly more ICAM-1–stained microvessels (up to 97% of microvessels at 1.8 days) than the noninfarcted hemisphere ( P &lt;.001), although the noninfarcted hemisphere (1.8 to 6.3 days) also showed higher ICAM-1 expression than controls. In the absence of ICAM-1 upregulation, macrophages (&gt;200/mm 2 ) were abundant in the core of neuronal damage at 17 and 18 days. Conclusions The striking upregulation of endothelial ICAM-1 expression, functioning in concert with chemotactic factors, may cause granulocyte infiltration during the first 3 days after stroke. This study may support the usage and timing of antibody infusions to block endothelial adhesion molecules in an attempt to reduce leukocyte-induced damage in stroke.
Correction: A Candidate Gene Approach Identifies the TRAF1/C5 Region as a Risk Factor for Rheumatoid Arthritis
Authors: Fina A. S Kurreeman, Leonid Padyukov, Rute B Marques, Steven J Schrodi, Maria Seddighzadeh, Gerrie Stoeken-Rijsbergen, Annette H. M van der Helm-van Mil, Cornelia F Allaart, Willem Verduyn, Jeanine Houwing-Duistermaat, Lars Alfredsson, Ann B Begovich, Lars Klareskog, Tom W. J Huizinga, Rene E. M Toes
Journal: PLoS Medicine (2007)

In Table 1, the allele ratio in column eight (Allele Ratios b : Cases, Controls) refers to allele A: allele B and not allele1:allele2 as described in footnote b, with Allele A being the Susceptibility Allele as denoted in column seven.
Vascular remodeling and the kallikrein-kinin system
Authors: Oscar A. Carretero
Journal: Journal of Clinical Investigation (2005)

Remodeling of the arterial wall occurs mainly as a consequence of increased wall stress caused by hypertension. In this issue of the JCI, Azizi et al. report that in humans with a kallikrein gene polymorphism that lowers kallikrein activity, the brachial artery undergoes eutrophic inward remodeling in the absence of hypertension or other hemodynamic changes. It has also been reported that alterations of the kallikrein-kinin system are associated with formation of aortic aneurysms. Conversely, after vascular injury, kinins mediate the beneficial effect of angiotensin-converting enzyme inhibitors that prevent neointima formation. These findings raise the intriguing possibility that decreased kallikrein-kinin system activity may play an important role in the pathogenesis of vascular remodeling and disease, while increased activity may have a beneficial effect.
Brain Dead Patients Are Still Whole Organisms
Authors: Nicholas Sadovnikoff, Daniel Wikler
Journal: The American Journal of Bioethics (2014)

"Brain Dead Patients Are Still Whole Organisms." The American Journal of Bioethics, 14(8), pp. 39–40 Notes1 . Oddly, Bernat observes (correctly, we believe) that “Brain death … remains poorly understood by the public and health professionals,” and “more work is necessary to establish its biophilosophical justification and to educate health professionals and the public” (XX). What weight then should be given to the absence of public outcry by a public so poorly educated and ignorant of the real issues?
Tuberculosis as an Endemic and Nosocomial Infection among the Elderly in Nursing Homes
Authors: William W. Stead, J.P. Lofgren, Emory Warren, Constance Thomas
Journal: New England Journal of Medicine (1985)

We studied reactivity to tuberculin skin testing in nearly all nursing home residents in Arkansas. Only 12 per cent of the 12,196 newly admitted residents were tuberculin positive, as compared with 20.8 per cent of the 13,441 residents who were first tested more than a month (mean, 30 months) after admission. The proportion of persons who were positive on initial testing varied greatly with the time spent in the home before testing. Those who were not reactive on initial testing had a 5 per cent rate of conversion for each year spent in a home with a known recent infectious case (within three years) and a 3.5 per cent rate for each year in a home with no recognized recent case. Active tuberculosis developed in only 1 of 534 persons with positive tuberculin tests or previous reactions who were treated with isoniazid, but in 79 (2.4 per cent) of 3270 persons who were not (P<0.001). The disease developed in only 1 (0.16 per cent) of 605 persons whose tests converted to positive and who were treated with isoniazid, as compared with 45 (5.9 per cent) of 757 whose tests converted but who were not treated (P<0.001). We conclude that new infection with tuberculosis is an important risk for nursing home patients and that greater care should be taken to detect and treat new infections before the disease develops and the infection spreads. (N Engl J Med 1985; 312:1483–7.)
Pacemaker Selection — The Changing Definition of Physiologic Pacing
Authors: Kenneth A. Ellenbogen, Mark A. Wood
Journal: New England Journal of Medicine (2005)

Almost 50 years after the first report of the use of cardiac pacing, in the Journal, 1 pacing is playing an increasingly important role in the management of cardiac disease. Cardiologists have evaluated single-chamber, dual-chamber, and triple-chamber pacemakers in patients with different types of conduction-system disease and underlying cardiac function. The goal of these increasingly complex pacing systems is to reproduce the normal electrical activation of the heart.Dual-chamber pacing confers potentially important hemodynamic advantages over ventricular pacing by linking the timing of atrial and ventricular contraction, a phenomenon called atrioventricular synchrony.2 In short-term and long-term studies, atrioventricular synchrony improves stroke . . .
Hepatocellular carcinoma for the non-specialist
Authors: T Kumagi, Y Hiasa, G M Hirschfield
Journal: BMJ (2009)

#### Summary points

Hepatocellular carcinoma is the third most common cause of cancer related mortality worldwide, and in the United Kingdom population data show that age standardised incidence rose from 1.4 to 3.9 per 100 000 people between 1975 and 2006 (http://info.cancerresearchuk.org/cancerstats/types/liver). Cirrhosis of the liver is the strongest predisposing factor—80-90% of cases arise from chronic liver disease. Furthermore, in cohort studies of patients with cirrhosis, hepatocellular carcinoma is the leading cause of liver related death.1 2 

#### Sources and selection criteria

We based this review on the available evidence presented in international consensus guidelines and cited in PubMed after searching with the terms “hepatocellular carcinoma”, “natural history”, “surveillance”, “screening”, “outcome”, “treatment”, and “prevention”.

Worldwide rates of hepatocellular carcinoma (fig 1⇓) correlate with widespread infection with hepatitis B in Asia and Africa and hepatitis C in Western countries and Japan. These viral infections are the most common underlying causes of liver disease that predispose to hepatocellular carcinoma (box 1).

#### Box 1 Important risk factors for hepatocellular carcinoma



Fig 1 2002 estimates of age standardised incidence of hepatocellular carcinoma. Incidence varies 14-fold across the world for men and 10-fold for women. The disease is still rare in the UK—140th of the 172 countries worldwide for men and 136th for women. Adapted, with permission, from Cancer Research UK



Chronic …
Lipoprotein(a) is an independent risk factor for coronary artery disease in NIDDM patients in South India.
Authors: V Mohan, R Deepa, S P Haranath, G Premalatha, M Rema, N G Sastry, E A Enas
Journal: Diabetes Care (1998)

OBJECTIVE: Asian Indians have been reported to have very high prevalence rates of coronary artery disease (CAD) in the absence of traditional risk factors. Recently, elevated levels of lipoprotein(a) [Lp(a)] have been reported to be associated with premature CAD in migrant Asian Indians. However, there are very little data regarding Lp(a) in CAD patients from the Indian subcontinent and virtually none in individuals with NIDDM. The objective of this study was to assess the role of Lp(a) as a marker for CAD in South Indian NIDDM patients. RESEARCH DESIGN AND METHODS: We estimated serum Lp(a) in 100 control subjects, 100 NIDDM patients without CAD, and 100 NIDDM patients with CAD. Lp(a) values were transformed into natural logarithms. Statistical analysis included Student's t test, one-way analysis of variance, and chi2 test. Multiple logistic regression analysis was used to identify associations with CAD. RESULTS: Lp(a) levels were significantly higher in NIDDM patients with CAD compared with NIDDM patients without CAD and control subjects (geometric mean 24.6, 15.1, and 19.4 mg/dl, respectively, P &amp;lt; 0.05). Results of logistic regression analysis showed that Lp(a), age, and HDL were associated with CAD. In NIDDM patients with CAD, there was no correlation between Lp(a) and serum cholesterol, triglyceride, or HDL cholesterol levels, but there was a weak association with LDL cholesterol and systolic blood pressure. CONCLUSIONS: The data suggests that serum Lp(a) is an independent risk factor for CAD in NIDDM patients in South India.
Combined Trifocal and Microsurgical Testicular Sperm Extraction Is the Best Technique for Testicular Sperm Retrieval in “Low-Chance” Nonobstructive Azoospermia
Authors: Marcelo Marconi, Andreas Keudel, Thorsten Diemer, Martin Bergmann, Klaus Steger, Hans-Christian Schuppe, Wolfgang Weidner
Journal: European Urology (2012)
Abstract C49: AKT inhibitor has potent antitumor activity in human lung cancer xenograft models
Authors: Naheed Banu, Tej Hiran, K. Chafai Fadela, Krishna Menon
Journal: Cancer Research (2009)

Abstract Lung cancer accounts for more than 215,000 new cases annually in the United States, and is the single largest cause of cancer death accounting for more than 130,000 deaths each year. Non-small cell lung cancer (NSCLC) accounts for 80% of all bronchogenic neoplasms with 90% of diagnosed patients dying within five years; therefore, new therapies are strongly desired. Effective therapies will come from a more detailed understanding of the molecular mechanisms underlying both the disease and the clinical response. We are developing a novel molecule, termed Kevetrin™, which was effective in reducing tumor growth in human lung cancer xenograft models while being well-tolerated. Kevetrin appeared to exert its anti-tumor activity by lowering levels of activated AKT also known as protein kinase B, of the AKT signal transduction pathway resulting in reduced tumor cell survival. Activated AKT was measured by a sandwich ELISA specific for phosphorylated AKT protein. Kevetrin was also evaluated for anti-tumor activity in vivo in the NCI-H1975 and A549 lung xenograft tumor models. Tumor-bearing nude mice were treated intravenously (IV) with either 200 mg/kg Kevetrin three times every other day or 22 mg/kg paclitaxel four times every other day. After Kevetrin was incubated with cells in vitro, phosphorylated AKT levels were reduced leading us to test for anti-tumor activity in vivo. Results with NCI-H1975 tumors showed that Kevetrin significantly delayed median tumor growth by 34 days (142%) in the first experiment and 28 days (156%) in a repeat experiment compared to controls, whereas the tumor growth delay (TGD) of paclitaxel was just 4 days (17%) and 14 days (78%), respectively. No weight loss occurred during treatment with Kevetrin. Results with A549 tumors showed that Kevetrin significantly delayed median tumor growth by 11 days (33%) in the first experiment and 30 days (111%) in a repeat experiment compared to controls, whereas the TGD of paclitaxel was just 0 days (0%) and 3 days (11%), respectively. In this study, Kevetrin resulted in &amp;lt;5% weight loss during treatment. These results showed that Kevetrin exerted potent anti-tumor activity against two human lung xenograft tumor models, NCI-H1975 and A549, at a dose and schedule that was well-tolerated as indicated by a small transient weight loss during treatment. NCI-H1975 have the T790M and L858R mutations in epidermal growth factor receptor (EGFR) and A549 have the K-ras mutation and overexpress STAT3 and Nrf2; these mutations are associated with resistance to standard chemotherapy. The reduction of activated AKT may be a mechanism by which Kevetrin overcame resistance and showed efficacy in these tumor models. These studies demonstrate that Kevetrin has promising potential for the treatment of lung carcinoma, particularly in cases where tumors have become resistant to standard chemotherapy. Citation Information: Cancer Res 2009;69(23 Suppl):C49.