tbuckley/cabot-search huggingface dataset:
Cephaloridine: A Nephrotoxic Drug
Authors: William M. Bennett
Journal: JAMA (1971)

<h3>To the Editor.—</h3> This LETTER is in response to an article by Dillon and Postlewait on the use of cephaloridine in patients with impaired renal function (<b>218</b>:250, 1971). The authors conclude that although 81 of 362 patients had renal impairment during courses of therapy with cephaloridine, the drug was not to be implicated as a causative factor in the renal injury. They state, without presenting any data, that elevation of blood urea nitrogen level was secondary to inadequate hydration, obstructive uropathy, or increased sources of nitrogenous products in the majority of these patients. We would choose to look at their data in a slightly different fashion. It is well known that hypotension and various toxic chemicals may be additive in the syndrome of acute tubular necrosis. Hollenberg et al<sup>1</sup>have shown that many nephrotoxic substances act by causing preferential cortical ischemia. Certainly hypotension with resultant catecholamine release also
Evaluating Multipollutant Exposure and Urban Air Quality: Pollutant Interrelationships, Neighborhood Variability, and Nitrogen Dioxide as a Proxy Pollutant
Authors: Ilan Levy, Cristian Mihele, Gang Lu, Julie Narayan, Jeffrey R. Brook
Journal: Environmental Health Perspectives (2013)

Although urban air pollution is a complex mix containing multiple constituents, studies of the health effects of long-term exposure often focus on a single pollutant as a proxy for the entire mixture. A better understanding of the component pollutant concentrations and interrelationships would be useful in epidemiological studies that exploit spatial differences in exposure by clarifying the extent to which measures of individual pollutants, particularly nitrogen dioxide (NO2), represent spatial patterns in the multipollutant mixture.We examined air pollutant concentrations and interrelationships at the intraurban scale to obtain insight into the nature of the urban mixture of air pollutants.Mobile measurements of 23 air pollutants were taken systematically at high resolution in Montreal, Quebec, Canada, over 34 days in the winter, summer, and autumn of 2009.We observed variability in pollution levels and in the statistical correlations between different pollutants according to season and neighborhood. Nitrogen oxide species (nitric oxide, NO2, nitrogen oxides, and total oxidized nitrogen species) had the highest overall spatial correlations with the suite of pollutants measured. Ultrafine particles and hydrocarbon-like organic aerosol concentration, a derived measure used as a specific indicator of traffic particles, also had very high correlations.Our findings indicate that the multipollutant mix varies considerably throughout the city, both in time and in space, and thus, no single pollutant would be a perfect proxy measure for the entire mix under all circumstances. However, based on overall average spatial correlations with the suite of pollutants measured, nitrogen oxide species appeared to be the best available indicators of spatial variation in exposure to the outdoor urban air pollutant mixture.
Fibroblast Growth Factor-2 Decreases Metabolic Coupling and Stimulates Phosphorylation as Well as Masking of Connexin43 Epitopes in Cardiac Myocytes
Authors: Bradley W. Doble, Yijing Chen, Denis G. Bosc, David W. Litchfield, Elissavet Kardami
Journal: Circulation Research (1996)

Cardiac gap junction (GJ) channels, composed of connexins, allow electrical and metabolic couplings between cardiomyocytes, properties important for coordinated action of the heart as well as tissue homeostasis and control of growth and differentiation. Fibroblast growth factor-2 (FGF-2) is an endogenous growth-promoting protein, believed to participate in the short- and long-term responses of the heart to injury. We have examined short-term effects of FGF-2 on cardiac myocyte GJ–mediated metabolic coupling, using cultures of neonatal rat cardiomyocytes. FGF-2 decreased coupling between cardiomyocytes assessed by scrape dye loading as well as microinjection and dye transfer within 30 minutes of administration. Genistein blocked the effects of FGF-2. To determine the mechanism, we next assessed the effect of FGF-2 on expression, distribution, and phosphorylation of connexin43 (Cx43), which is a major cardiomyocyte connexin. FGF-2 did not affect Cx43 mRNA or protein accumulation and synthesis, and it did not change Cx43 localization at sites of intercellular contact as assessed by immunostaining with a polyclonal anti-Cx43 antibody raised against a synthetic peptide containing residues 346 to 363 of Cx43. FGF-2, however, decreased staining intensity at sites of intermyocyte contact when a monoclonal anti-Cx43 antibody was used, suggesting a localized masking of epitope(s) recognized by the monoclonal but not the polyclonal antibody. These epitopes appear to reside within residues 261 to 270 of Cx43, as indicated by full quenching of monoclonal antibody staining with synthetic peptides. In addition, FGF-2 induced a more than twofold increase in Cx43 phosphorylation. Phosphoamino acid analysis indicated increased phosphorylation of Cx43 on serine residues. Although tyrosine phosphorylation of Cx43 was not detected in either treated or control cells, a fraction of Cx43 was immunoprecipitated with anti–phosphotyrosine-specific antibodies in FGF-2–treated myocytes, suggesting interaction (and hence coprecipitation) with phosphotyrosine-containing protein(s). In conclusion, we have identified Cx43 and intercellular communication as targets of FGF-2–triggered and tyrosine phosphorylation–dependent signal transduction in cardiac myocytes. It is suggested that phosphorylation of Cx43 on serine induced by FGF-2 contributes to decreased metabolic coupling between cardiomyocytes.
Case 5-1975
Authors: Louis Weinstein, Benjamin Castleman
Journal: New England Journal of Medicine (1975)

Presentation of CaseA 70-year-old woman was admitted to the hospital because of fever.Three months previously she became anorectic, with loss of weight. Four days before entry fever, chilliness, retching and explosive diarrhea developed. She complained of diffuse pains in the chest, legs and joints. Two days before admission she became confused.There was no history of dark urine, jaundice, bleeding or exposure toa communicable disease.The temperature was 39.4°C, the pulse 110, and the respirations 18. The blood pressure was 120/80 mm Hg.On examination the patient appeared acutely ill and confused. No cutaneous lesions were observed. There . . .
SEQUENTIAL OPTICAL COHERENCE TOMOGRAPHY IMAGING POST PROCEDURE, AT 6, 12, 24 AND 36 MONTHS IN THE ABSORB COHORT B TRIAL: A LIGHT INTENSITY ANALYSIS TO ASSESS THE BIORESORPTION PROCESS OF EVEROLIMUS-ELUTING PLLA SCAFFOLD
Authors: Shimpei Nakatani, Yoshinobu Onuma, Yuki Ishibashi, Robert van Geuns, Bernard De Bruyne, Dariusz Dudek, Evald Christiansen, Pieter Smits, Bernard Chevalier, Dougal McClean, Jacques Koolen, Stephan Windecker, Ian Meredith, Laura Perkins, Richard Rapoza, Hector Garcia Garcia, John Ormiston, Patrick Serruys
Journal: Journal of the American College of Cardiology (2014)
829 SAFETY AND EFFICACY OF THE EXTRACORPOREAL LIVER ASSIST DEVICE (ELAD®) IN PATIENTS WITH ACUTE ON CHRONIC LIVER FAILURE
Authors: D.J. Hillebrand, R.T. Frederick, W.W. Williams, R.S. Brown, L.M. Napotilano, H.S. Te, J.M. Millis, R.A. Ashley, P.J. Pockros
Journal: Journal of Hepatology (2010)
Correlates of Age Onset of Type 2 Diabetes Among Relatively Young Black and White Adults in a Community
Authors: Quoc Manh Nguyen, Ji-Hua Xu, Wei Chen, Sathanur R. Srinivasan, Gerald S. Berenson
Journal: Diabetes Care (2012)

The risk factors for middle-age onset of type 2 diabetes are well known. However, information is scant regarding the age onset of type 2 diabetes and its correlates in community-based black and white relatively young adults.
Small-Bowel Perforations Related to Endoscopic Retrograde Cholangiopancreatography (ERCP) in Patients with Billroth II Gastrectomy
Authors: None Faylona, None Qadir, None Chan, None Lau, None Chung
Journal: Endoscopy (1999)

Endoscopic retrograde cholangiopancreatography (ERCP) is one of the mainstays in the diagnosis and treatment of hepatobiliary and pancreatic diseases, and is also increasingly used for patients with previous Billroth II gastrectomy. The aim of this study was to review our experience of ERCP in patients with Billroth II gastrectomy, and the complications associated with this procedure.The records of 110 patients with Billroth II gastrectomy, treated between January 1993 and December 1997, were received retrospectively. Details noted included indications for ERCP, therapeutic interventions, causes of failure, and complications.A total of 110 patients underwent ERCP; the total number of ERCP attempts was 185. The major indications for ERCP were cholangitis (31%), common bile duct stones (22%), and jaundice (15%). The endoscope was successfully passed up to the papilla in 134 examinations (71%), and selective cannulation was successful in 122 of these (66%). There were 63 (34%) failed ERCP attempts. Causes of failure were: difficulty in entering the afferent loop (n = 19, 10%), failure to enter the duodenum (n = 23, 12%), endoscope-related bowel perforation (n = 9, 5%), and failed cannulation (n = 10, 6%). The other two failures were caused by desaturation in the patient, and inability to distend the duodenum. The major complication of the procedure was perforation, which occurred in 11 examinations (6%). Of these perforations, nine occurred in the small bowel while the endoscope was being manipulated through the afferent loop; these patients required laparotomy. Two patients had retroduodenal perforations, one occurring after sphincterotomy and one after cannulation. Both patients were successfully managed conservatively. Three patients suffered bleeding after sphincterotomy (3/185 procedures, 1.6%), and one patient developed acute pancreatitis. These were managed conservatively. The overall complication rate was 8%. There were two deaths among the patients with small-bowel perforations, and consequently an overall mortality rate of 1% (2/185 procedures).Most complications of ERCP in patients with previous Billroth II gastrectomy were caused by bowel perforation while the endoscope was being manipulated through the afferent limb. Such perforations are intraperitoneal and require surgical intervention.
Epidermoid Carcinoma of the Gum: A 20-Year Survey
Authors: B. Cady, D. Catlin
Journal: CA A Cancer Journal for Clinicians (1970)

Between 1942 and 1961, 606 patients with epidermoid cancer of the gum were studied. Three quarters were men, and 95% of them smoked; one half of the women did not. Sixty-three per cent had clinically localized disease, and 51% had primary lesions under 3 cm in diameter. Absolute survival rose from 27% in 1946 to 50% in 1961. Determinate survival rose from 35% to 64%. Localized cancer of the gum under 3 cm in diameter was cured in over 80% of patients. Lesions accompanied by only submandibular lymph node metastases were cured in 80%. If nodal metastases occurred in the jugular chain, 38% were salvaged. Gum cancer over 5 cm had a poor outlook, and if accompanied by jugular node metastases was uniformly fatal. This report demonstrates that currently gum cancer presents with smaller diameter primary lesions and higher and more favorable lymph node metastases to account for the increasing survival. Thus the changing patterns of disease produced the improving survival. Categories of patients in whom adjunctive measures and elective neck dissections should be strongly considered are outlined.
INTENSIVE INSULIN SHOCK THERAPY—A FIVE-YEAR SURVEY
Authors: EARL P. BRANNON, WALTER L. GRAHAM
Journal: American Journal of Psychiatry (1955)

In this series 528 cases—the great majority of them schizophrenics—were treated with intense deep insulin coma. The functional recovery rate was between 47.4% and 71.3% among different schizophrenic groups and between 77.7% and 100% among manic-depressive groups. It is difficult to compare results between male and female patients because of the small number of the latter. However, the results in both groups seem to be about even. Comparing white and Negro patients, the white group has a somewhat higher functional recovery rate. Most of the treatment patients were between 25 and 35 years of age. The recovery rate is highest in the younger age groups, particularly in the group of 20-25 years of age. The rate of recovery decreases with the length of illness prior to institution of treatment. The rate of recovery decreases further with length of hospitalization prior to institution of treatment. Of 528 treated cases, 266 are still out of the hospital.
MicroRNA-26a suppresses angiogenesis in human hepatocellular carcinoma by targeting hepatocyte growth factor-cMet pathway
Authors: Xin Yang, Xiao-Fei Zhang, Xu Lu, Hu-Liang Jia, Lei Liang, Qiong-Zhu Dong, Qing-Hai Ye, Lun-Xiu Qin
Journal: Hepatology (2013)

MicroRNA (miR)-26a can suppress tumor growth and metastasis of hepatocellular carcinoma (HCC). Since angiogenesis is important for tumor growth and metastasis, we investigated the possible roles of miR-26a in tumor angiogenesis. Down-regulation of miR-26a was found to correlate with an increased angiogenic potential of HCC. Through gain- and loss-of-function studies, miR-26a was demonstrated to significantly inhibit vascular endothelial growth factor A (VEGFA) expression in HCC cells and then suppress the promoting effects of HCC cells on in vitro proliferation, migration, and capillary tube formation of endothelial cells, as well as in vivo tumor angiogenesis of HCC. Hepatocyte growth factor (HGF) was identified as a target of miR-26a. HGF simulation antagonized the effects induced by miR-26a up-regulation. In contrast, silencing HGF induced similar effects to miR-26a. We further found that miR-26a exerted its antiangiogenesis function, at least in part, by inhibiting HGF-hepatocyte growth factor receptor (cMet) and its downstream signaling pathway, in turn, suppressing VEGFA production in HCC cells and impairing VEGFR2-signaling in endothelial cells. HCC patients who had high miR-26a, low HGF, low VEGFA, or low microvessel density (MVD) in tumor tissues had a better prognosis with longer overall survival (OS) and time to recurrence (TTR). In multivariate analysis, miR-26a, or in combination with HGF, was demonstrated to be an independent prognostic indicator for OS and TTR of HCC patients. Conclusion : miR-26a could suppress tumor angiogenesis of HCC through HGF-cMet signaling, and it is a new hopeful therapeutic target and prognostic marker for HCC. (Hepatology 2014;59:1874–1885)
Intraperitoneal Chemotherapy Comes of Age
Authors: Stephen A. Cannistra
Journal: New England Journal of Medicine (2006)

Patients with advanced epithelial ovarian cancer typically receive intravenous taxane and platinum-based chemotherapy in an attempt to eradicate residual disease after surgical debulking. This treatment yields overall median survivals of approximately 37 months in patients with suboptimally debulked disease (residual tumor, >1.0 cm in diameter) and 49 months in those with optimally debulked disease (residual tumor, ≤1.0 cm in diameter).1 Despite high response rates, in most patients relapse occurs, and efforts to improve treatment by escalating the doses of intravenous chemotherapy have been largely unsuccessful.2 In contrast to intravenous drug administration, the intraperitoneal route is capable of achieving high local . . .
Infection by Mycobacterium Avium Intracellulare in AIDS: Endoscopic Duodenal Appearance Mimicking Whipple's Disease
Authors: J. L. Vázquez-lglesias, J. Yañez, J. Durana, F. Arnal
Journal: Endoscopy (1988)

We report the case of a 24-year-old woman who presented with diarrhea, weight loss and abdominal lymph node enlargement. A diagnosis of infection by Mycobacterium avium intracellulare with a clinical picture similar to Whipple's disease was established. The endoscopic study of the duodenum revealed multiple yellow nodules that became confluent in the second portion, entirely replacing the normal mucosa. These endoscopic findings have not been described previously in intestinal infection by Mycobacterium avium intracellulare.
Carboxylated Calcium-Binding Proteins and Vitamin K
Authors: Paul M. Gallop, Jane B. Lian, Peter V. Hauschka
Journal: New England Journal of Medicine (1980)

FIFTY years ago, Heinrik Dam, while a doctoral student under Rudolf Schönheimer at the University of Freiberg, was investigating cholesterol bio-synthesis in chicks. He prepared fat-free diets by extracting the feed with organic solvents and noted that the chicks raised on this diet for about three weeks acquired hemorrhagic disease. Returning to Denmark, Dam and his colleagues concluded that absence of a fat-soluble factor caused a defect in blood coagulation through the loss of functional prothrombin. No other vitamin or nutrient known at that time was able to replace the fat-soluble component, which he called vitamin K (Koagulations Vitamin).In . . .
Insulin Receptor Substrate–4 Signaling in Quiescent Rat Hepatocytes and in Regenerating Rat Liver
Authors: Oscar Escribano, María Dolores Fernández-Moreno, José Antonio Zueco, Cesar Menor, Jesus Fueyo, Rosa María Ropero, Inés Diaz-Laviada, Irene D. Román, Luis G. Guijarro
Journal: Hepatology (2003)

This study was designed to characterize insulin receptor substrate–4 (IRS–4) in isolated rat hepatocytes and to examine its role in liver regeneration. Subcellular fractionation revealed that 85% of IRS–4 is located at isolated hepatocyte plasma membranes. The distribution of IRS–4 among intracellular compartments remained unchanged in insulin–stimulated cells. Two bands corresponding to 145 and 138 kd were observed in immunoblotting experiments. Immunoprecipitation of hepatocyte lysates with a highly specific antibody against IRS–4 led to an insulin and insulin–like growth factor 1 (IGF–1)–dependent increase in phosphotyrosine residues of the 145–kd band. IRS–4 was found to be associated with Src homology 2 (SH2) domain–containing proteins (phosphatidylinositol 3–kinase [PI 3–kinase] and Src homology phosphatase [SHP–2]) and with protein kinase C ζ (PKC ζ). Insulin and IGF–1 elicited a rapid and dose–dependent binding of these 3 proteins to IRS–4. These data suggest that IRS–4 is insulin–/IGF–1–activated by phosphorylation and not by translocation, inducing the recruitment of SH2 domain–containing proteins and PKC ζ to the membrane. To evaluate the possible role of IRS–4 in liver regeneration, we also examined this system after partial hepatectomy (PH). One day after PH, IRS–1 expression increased, consistent with a stimulatory role in the regenerative process, whereas it decreased 7 days after liver resection. This drastic IRS–1 depletion occurred at the expense of increased IRS–2 and IRS–4 expression 7 days after PH. In addition, at this period of time after surgery, the in vivo insulin stimulation of remnant rat livers showed an increase in IRS–4/PI 3–kinase association. Given that 1 and 7 days after PH isolated hepatocytes responded similarly to insulin in terms of induced cell proliferation, a compensatory role is proposed for IRS–2/4 induction. In conclusion, IRS–4 is activated by insulin and IGF–1–like IRS–1 in rat hepatocytes, and the induced expression of IRS–4 is a compensatory mechanism that plays a role in conditions of liver regeneration.
TUBERCULIN IN TUBERCULOUS LARYNGITIS
Authors: B. T. McMahon
Journal: JAMA (1933)

To the Editor:  —At a recent meeting of the New York State Medical Society tuberculin therapy was advocated, in the Section on Otolaryngology, for tuberculous laryngitis. In the discussion, no reference was made to the great danger that tuberculin is liable to provoke severe and extensive focal reactions. It is well known that pulmonary tuberculosis may be present without giving rise to conscious symptoms, and, in children, unsuspected tuberculous infiltration of the tracheobronchial lymph glands is not uncommon. Injudicious use of tuberculin in such cases might lead to serious consequences. Even in the fields of dermatology and ophthalmology, in which tuberculin has proved its usefulness, this possibility should be kept in mind and tuberculin therapy should not be instituted without previously determining whether there exists in the lungs a type of lesion contraindicating it. Particularly is this true in tuberculous laryngitis, which, for all practical purposes, is secondary to pulmonary
Response to Letter Regarding Article, “Ischemic Conditioning Protects the Uremic Heart in a Rodent Model of Myocardial Infarction”
Authors: Kieran McCafferty, Conor J. Byrne, Julius Kieswich, Steven Harwood, Petros Andrikopoulos, Martin Raftery, Christoph Thiemermann, Muhammad M. Yaqoob
Journal: Circulation (2012)

Conditioning Protects the Uremic Heart in a Rodent Model of Myocardial Infarction"We are grateful to Csont and Ferdinandy for their letter in response to our recent article. 1 We are encouraged by their work, which demonstrated the cardioprotective effect of postconditioning 10 weeks after a subtotal nephrectomy.The 4-week subtotal nephrectomy model is the most widely used model of chronic uremia and displays many of the common characteristics that define the uremic phenotype.The 4-week subtotal nephrectomy model leads to animals that are growth restricted, hypertensive, anemic, dyslipidemic, proteinuric, and polyuric with a high fractional excretion of sodium and histological evidence of left ventricular hypertrophy (unpublished data, McCafferty and Byrne, 2011).In addition to our own experience, the 4-week subtotal nephrectomy model has been shown to lead to hypocalcemia, hyperphosphatemia, and hyperparathyroidism, 2 bioenergetic failure, 3 and reduced capillary density and myocardial fibrosis. 4e agree with Csont and Fernandy that there appears to be a complex interaction between the duration of diabetes mellitus and myocardial ischemia tolerance in animals.The temporal changes in ischemia tolerance in the context of diabetes mellitus also appear to mirror the effects of conditioning strategies with a resistance to conditioning strategies developing over time.However, unlike diabetes mellitus, underlying uremia does not lead to an early increased ischemic tolerance: even at 4 weeks the uremic heart is more susceptible to injury, and despite this reduced ischemia tolerance, there is no resistance to ischemic conditioning.We therefore suggest that not all animal models of comorbidities behave in the same way either in terms of ischemia tolerance or resistance to ischemic conditioning strategies and so should be considered separately.Although we agree that extending the duration of uremia may enhance our understanding of the complex interactions between uremia and cardiovascular disease, we feel that our relatively short-term models provide a compelling model of human disease.Finally, we await the outcome of the Renal Protection Against Ischaemia Reperfusion in Transplantation (REPAIR) trial, 5 which will provide insights into the efficacy of remote ischemic preconditioning in the context of end-stage renal failure in humans.
The shifting debate on trial data transparency
Authors: E. Davies
Journal: BMJ (2013)

The BMJ is currently running a campaign for trial data transparency (www.bmj.com/open-data), so it is fair to say that we do not approach this week’s Head to Head feature without any interest of our own.

However, it is also true that there is more than one side to this story. With that in mind, we commissioned Ben Goldacre, AllTrials.net campaigner, and John Castellani, president and …