tbuckley/cabot-search huggingface dataset:
Regenerative changes in hepatic morphology and enhanced expression ofCYP2B10 andCYP3A during daily administration of cocaine
Authors: P Pellinen, F Stenback, A Kojo, P Honkakoski, H V Gelboin, M Pasanen
Journal: Hepatology (1996)

The effects of daily cocaine administration for up to 14 days were studied in terms of hepatic morphology and the expression of cytochrome P450 ( CYP ) enzymes in the mouse liver. Daily intraperitoneal doses of 60 mg/kg of cocaine for 3 days induced severe hepatocellular necrosis in the pericentral zone and decreased activities of CYP 1A2, CYP 2A4/5, and CYP 2Cx. The microsomal CYP 2B10 protein content was increased by about 2.5-fold, but 2B10-dependent 7-pentoxyresorufin O-dealkylase (PROD) activity was barely detectable. Five or seven daily cocaine doses caused prominent pericentral inflammation and a significant (up to 14-fold) increase in the microsomal protein content and PROD activity. An increase in microsomal CYP 3A was also evident, but CYP 2A5 and CYP 1A2 still remained at a low level. Immunohistochemical examination showed that the relative induction of CYP 2B10 and CYP 3A after treatment with cocaine was strongest in perivenous hepatocytes. Immunoinhibition experiments showed that CYP 2B10 accounted for catalysis of only 15% to 20% of the enhanced microsomal cocaine N-demethylase (CNDM) activity, which correlated well with immunoreactive 3A protein, and could be blocked 70% to 90% by triacetyloleandomycin. After 10 or 14 daily doses of cocaine, regenerative changes with hepatocyte ballooning were observed, coinciding with increases in CYP 1A2, CYP 2A4/5, and CYP 3A. These results suggest the following: (1) cocaine enhances its own cytochrome P450-dependent metabolism; (2) increased production of norcocaine in microsomes is catalyzed mainly by CYP 3A enzyme(s), whereas 2B10, although markedly increased by cocaine treatment, has only a minor role in cocaine hepatotoxicity; and (3) despite increased microsomal CNDM activity, cocaine-induced liver injury is reversible in mice.
Small-Bowel Ulcers With Thiazide and Potassium
Authors: Marcus D. McDivitt
Journal: JAMA (1965)

<h3>To the Editor:—</h3> After reading "Small Bowel Ulceration Apparently Associated with Thiazide and Potassium Therapy" by Baker et al (<i>JAMA</i><b>190</b>:586 [Nov 16] 1964), I remembered that I had treated a patient with a similar course in 1963 and 1964. This 65-year-old white male had had numerous hospital admissions since 1956 for the treatment of hypertensive cardiovascular disease associated with angina pectoris, paroxysmal atrial fibrillation, and, in 1958, an acute posterior myocardial infarction, after which he was treated with bishydroxycoumarin (Dicumarol). On April 20, 1963, he visited my office, complaining of severe bouts of angina pectoris. Blood pressure was 180/110 mm Hg. He had been taking nitroglycerin, 0.4 mg sublingually, and bishydroxycoumarin, 75-100 mg daily. I started him on a regimen of Esidrix-K (hydrochlorothiazide with potassium chloride), 50-1,000 mg, one tablet daily, and papaverine hydrochloride, 30 mg four times a day. He continued the use of nitroglycerin and bishydroxycoumarin as
On the Structure of the Luteinizing Hormone/Chorionic Gonadotropin Receptor*
Authors: MARIO ASCOLI, DEBORAH L. SEGALOFF
Journal: Endocrine Reviews (1989)

In this review we have tried to argue that the evidence indicating that the LH/CG receptor is composed of a single polypeptide is stronger than the evidence indicating that the LH/CG receptor is a more complex structure composed of several subunits. Clearly, however, this issue has not been resolved and probably will not be resolved by performing additional experiments similar to those summarized here. It is our opinion that this issue will be resolved only by 1) reconstitution experiments in which the ability of the purified LH/CG receptor to bind hCG and activate adenylyl cyclase activity is tested; and/or 2) isolation and expression of a full length complementary DNA (cDNA) for the LH/CG receptor and the demonstration of hCG binding and adenylyl cyclase activation by the expressed receptor. Similar experiments will also clarify the proposed structures for the FSH and TSH receptors. As the second decade of work on the LH/CG receptor draws to an end it appears that these experiments are now possible, and hopefully a resolution of the existing controversy will be forthcoming in the near future.
R1626 plus peginterferon Alfa-2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin
Authors: Paul J. Pockros, David Nelson, Eliot Godofsky, Maribel Rodriguez-Torres, Gregory T. Everson, Michael W. Fried, Reem Ghalib, Stephen Harrison, Lisa Nyberg, Mitchell L. Shiffman, Isabel Najera, Anna Chan, George Hill
Journal: Hepatology (2008)

R1626, a prodrug of the hepatitis C virus (HCV) RNA polymerase inhibitor R1479, showed time-dependent and dose-dependent reduction of HCV RNA levels in a previous study. The present study evaluated the efficacy and safety of R1626 administered for 4 weeks in combination with peginterferon alfa-2a +/- ribavirin in HCV genotype 1-infected treatment-naive patients. Patients were randomized to: DUAL 1500 (1500 mg R1626 twice daily [bid] + peginterferon alfa-2a; n = 21); DUAL 3000 (3000 mg R1626 bid + peginterferon alfa-2a; n = 32); TRIPLE 1500 (1500 mg R1626 bid + peginterferon alfa-2a + ribavirin; n = 31); or standard of care (SOC) (peginterferon alfa-2a + ribavirin; n = 20). At 4 weeks HCV RNA was undetectable (<15 IU/mL) in 29%, 69%, and 74% of patients in the DUAL 1500, DUAL 3000, and TRIPLE 1500 arms, respectively, compared with 5% of patients receiving SOC, with respective mean reductions in HCV RNA from baseline to week 4 of 3.6, 4.5, 5.2, and 2.4 log(10) IU/mL. Synergy was observed between R1626 and peginterferon alfa-2a and between R1626 and ribavirin. There was no evidence of development of viral resistance. Adverse events (AEs) were mainly mild or moderate; seven patients had nine serious AEs (including one patient with one serious AE in SOC). The incidence of Grade 4 neutropenia was 48%, 78%, 39%, and 10% in DUAL 1500, DUAL 3000, TRIPLE 1500, and SOC, respectively, and was the main reason for dose reductions.A synergistic antiviral effect was observed when R1626 was combined with peginterferon alfa-2a +/- ribavirin; up to 74% of patients had undetectable HCV RNA at week 4. Dosing of R1626 was limited by neutropenia; a study of different dosages of R1626 in combination with peginterferon alfa-2a and ribavirin is underway.
13CO2 breath test to measure the hydrolysis of various starch formulations in healthy subjects.
Authors: M Hiele, Y Ghoos, P Rutgeerts, G Vantrappen, K de Buyser
Journal: Gut (1990)

13CO2 starch breath test was used to study the effect of physicochemical characteristics of starch digestion. As starch is hydrolysed to glucose, which is subsequently oxidised to CO2, differences in 13CO2 excretion after ingestion of different starch products must be caused by differences in hydrolysis rate. To study the effect of the degree of chain branching, waxy starch, containing 98% amylopectin, was compared with high amylose starch, containing 30% amylopectin, and normal crystalline starch, containing 74% amylopectin. The effect of the extent of gelatinisation was studied by comparing extruded starch and crystalline starch. Finally, the possible inhibitory effect of adding wheat fibre to extruded starch on the hydrolysis rate was studied. The 13CO2 excretion from two to four hours after intake of crystalline starch was significantly lower than that of extruded starch. Waxy starch was hydrolysed much faster than high amylose starch, but there was no significant difference between waxy starch and normal crystalline starch. Addition of wheat fibre did not influence the hydrolysis rate. The 13CO2 starch breath test is an attractive test for the study of factors affecting carbohydrate assimilation.
A delayed bone–tendon junction healing model established for potential treatment of related sports injuries
Authors: L Wang, L Qin, W-H Cheung, H-B Lu, X-H Yang, K-S Leung, M W-N Wong, K-M Chan
Journal: British Journal of Sports Medicine (2008)

Animal models for the study of tendinopathy and bone-tendon (B-T) junction repair have been established in the past for sports medicine research. As healing at the B-T junction is difficult and sometimes delayed, establishing a delayed B-T healing experimental model is therefore essential to study the efficacy of potential biophysical and biological interventions for treatment of B-T junction healing.To test the hypothesis that a delay in B-T healing could be modelled by shielding the B-T healing interface for the initial few weeks.Using an established partial patellectomy model in rabbits, the B-T healing interface was shielded with a latex slice for the first 4 postoperative weeks in mature female rabbits. The characteristics of delay in B-T repair (n = 10) compared with controls (n = 10) were evaluated at 8 and 12 postoperative weeks.Radiology showed consistent delay in osteogenesis at the healing interface in all samples in the delayed healing group; growth of new bone was only 25.8% and 50.1% of that in the control group at weeks 8 and 12, respectively. Bone mineral density was 56.0% lower in the delayed healing group at week 8, but this difference diminished at week 12. The quality of B-T healing was poor in the delayed healing group, with 22.9% and 24.2% lower failure load than the control group at weeks 8 and 12, respectively. The healing quality was also reflected by histological findings.A delayed B-T healing experimental model was established for the first time for future sports medicine research.
The International Vitreomacular Traction Study Group Classification of Vitreomacular Adhesion, Traction, and Macular Hole
Authors: Jay S. Duker, Peter K. Kaiser, Susanne Binder, Marc D. de Smet, Alain Gaudric, Elias Reichel, SriniVas R. Sadda, Jerry Sebag, Richard F. Spaide, Peter Stalmans
Journal: Ophthalmology (2013)
Evaluation of Endoscopic Mucosal Resection for Laterally Spreading Rectal Tumors
Authors: S. Tamura, K. Nakajo, Y. Yokoyama, K. Ohkawauchi, T. Yamada, Y. Higashidani, T. Miyamoto, H. Ueta, S. Onishi
Journal: Endoscopy (2004)

Background and Study Aims: We undertook this retrospective study to evaluate the frequency and prognosis of endoscopic treatment of laterally spreading tumors (LSTs) in the rectum. The recurrence rate for lesions of the lower rectum was compared with that of the upper rectum. Patients and Methods: During the period from July 1989 to June 2002, a total of 1237 rectal tumors were detected. LSTs accounted for 6.9 % (85/1237) of all rectal tumors. A total of 224 tumors of the lower rectum were detected among the 1237 rectal tumors. LSTs accounted for 16.1 % (36/224) of all the lower rectal tumors. From 85 LST lesions, 67 were evaluated for their prognosis after endoscopic mucosal resection (EMR). Patients whose LSTs had been resected were followed up by endoscopy at the following frequencies: once 15 (22.4 %); twice (more than 1 year), 20 (29.9 %); three times (more than 3 years), 21(31.3 %); and four times or more (more than 5 years), 11 (16.4 %). Results: A total of 67 patients with endoscopically treated LSTs were followed up by endoscopy. We observed recurrences in two lesions of the upper rectum (2/38, 5.3 %) and five lesions of the lower rectum (5/29, 17.2 %) (P = 0.2364); all seven lesions were resected piecemeal. LSTs whose horizontal margin reached the pectinate line frequently recurred in the lower rectum, at a rate of 80 % (4/5). However, all patients were completely cured by additional endoscopic resections, the greatest number of treatments being four. Conclusion: For early detection of recurrence and successful endoscopic cure, further colonoscopic examination within a few months after the first treatment is necessary.
Free-Floating Iris Cyst
Authors: Megan E Collins, Seenu M Hariprasad
Journal: New England Journal of Medicine (2010)

A 7-year-old girl was referred for evaluation of an iris lesion in her left eye. The patient wore eyeglasses, but her ocular and medical histories were otherwise unremarkable. The lesion was first noticed during a routine eye examination 3 months earlier; the parents stated that it was not present at birth. The patient had no history of trauma, surgery, infection, or travel. She reported that the spot in her eye moved when she tilted her head. Slit-lamp examination revealed a free-floating, spherical, translucent cyst, 1.5 mm in diameter, in the anterior chamber (Panel A). Gonioscopic examination confirmed that the cyst . . .
High phosphate directly affects endothelial function by downregulating annexin II
Authors: Giovana Seno Di Marco, Maximilian König, Christian Stock, Anne Wiesinger, Uta Hillebrand, Stefanie Reiermann, Stefan Reuter, Susanne Amler, Gabriele Köhler, Friedrich Buck, Manfred Fobker, Philipp Kümpers, Hans Oberleithner, Martin Hausberg, Detlef Lang, Hermann Pavenstädt, Marcus Brand
Journal: Kidney International (2012)
PDQ Usage Up
Authors: M. J. Zerbe
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article PDQ Usage Up Get access Michael J. Zerbe Michael J. Zerbe Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 7, 4 April 1990, Page 549, https://doi.org/10.1093/jnci/82.7.549-a Published: 04 April 1990
To err was fatal
Authors: C. Fonseka
Journal: BMJ (1996)

Error free patient care is the ideal standard but in reality unattainable. I am conscious of having made five fatal errors during the past 36 years.

After two years in state hospitals I joined the staff of my medical school in Colombo in 1962, holding the posts of lecturer, senior lecturer, associate professor, and professor of physiology. In all that time I have practised medicine because I believe that direct contact with patients makes my teaching more relevant.

In recounting the stories of my fatal errors the problem of guarding patient confidentiality arises. The BMJ has changed its policy from guarding anonymity to getting consent.1 In the most recent three of my five fatal errors, obtaining informed consent from relatives was easy. With regard to the first error, which occurred in 1960, and the second which occurred well over a quarter of a century ago, relatives could not be tracked down. So trying to achieve anonymity by changing names and some of the details was the best I could do. The British Medical Journal is not only British, it is also truly international. Wouldn't it be guilty of a species of ethical imperialism—the opposite of cultural relativism—if it refused to publish material about patients dead for nearly three decades or more, merely because written consent for publication had not been obtained from relatives who cannot be traced?

I find myself paralysed by doubts about how best to recount the case histories. It was Hippocrates who reputedly introduced the case history to medicine. The idea that diseases have a natural history is traceable to him.2 It is, of course, possible to recount the history of an illness without revealing much about the sufferer. To do so would not serve the purpose of this paper.

The 23 year old labourer …
Multiple Cerebral Aneurysms and Cardiac Myxoma
Authors: Charles Burton, John Johnston
Journal: New England Journal of Medicine (1970)

INTRACRANIAL aneurysms of peripheral cerebral arteries are rare. If trauma is not a consideration1 2 3 4 5 emboli or a local inflammatory process should be regarded as possible. In the nineteenth century it was believed that all intracranial aneurysms were due to septic (usually termed "niycotic"†) emboli.6 The case presented appears to be the first in which a metastatic tumor embolus has been implicated in the production of a cerebral aneurysm.Case ReportS.G., a 41-year-old woman, began to experience transient episodes of difficulty with speech, memory and temperament, as well as numbness and tingling of the right hand and occasional left-sided headache . . .
Functional interactions of T cells with endothelial cells: the role of CD40L-CD40-mediated signals.
Authors: M J Yellin, J Brett, D Baum, A Matsushima, M Szabolcs, D Stern, L Chess
Journal: The Journal of Experimental Medicine (1995)

CD40 is expressed on a variety of cells, including B cells, monocytes, dendritic cells, and fibroblasts. CD40 interacts with CD40L, a 30-33-kD activation-induced CD4+ T cell surface molecule. CD40L-CD40 interactions are known to play key roles in B cell activation and differentiation in vitro and in vivo. We now report that normal human endothelial cells also express CD40 in situ, and CD40L-CD40 interactions induce endothelial cell activation in vitro. Frozen sections from normal spleen, thyroid, skin, muscle, kidney, lung, or umbilical cord were studied for CD40 expression by immunohistochemistry. Endothelial cells from all tissues studied express CD40 in situ. Moreover, human umbilical vein endothelial cells (HUVEC) express CD40 in vitro, and recombinant interferon gamma induces HUVEC CD40 upregulation. CD40 expression on HUVEC is functionally significant because CD40L+ Jurkat T cells or CD40L+ 293 kidney cell transfectants, but not control cells, upregulate HUVEC CD54 (intercellular adhesion molecule-1), CD62E (E-selectin), and CD106 (vascular cell adhesion molecule-1) expression in vitro. Moreover, the kinetics of CD40L-, interleukin 1-, or tumor necrosis factor alpha-induced CD54, CD62E, and CD106 upregulation on HUVEC are similar. Finally, CD40L-CD40 interactions do not induce CD80, CD86, or major histocompatibility complex class II expression on HUVEC in vitro. These results demonstrate that CD40L-CD40 interactions induce endothelial cell activation in vitro. Moreover, they suggest a mechanism by which activated CD4+ T cells may augment inflammatory responses in vivo by upregulating the expression of endothelial cell surface adhesion molecules.
Laënnec vs. Laennec
Authors: William Dock
Journal: JAMA (1961)

<h3>To the Editor:—</h3> We hope Dr. Viets' plea, Laënnec vs. Laennec (<i>JAMA</i><b>176:</b>1052 [June 24] 1961), to drop the<i>tréma</i>(ë) from Lænnec's name, and to pronounce it Lennec or Lannec (as most Americans and Englishmen always do) will not deceive many as to how the great Breton pronounced his name. The name on his monument in Quimper and on his granite tombstone at Plouaré is spelled Laennec, for the<i>tréma</i>was not in use until the end of the 19th century, and in older French printing, words (<i>like païen</i>and<i>naïf</i>in modern books ) were printed with no sign over the vowel, which was given syllabic strength. In Lænnec's day, as today, the Latin diphthong Æ or æ was used when a single syllable was formed by these vowels. When the vowels were both enunciated they were printed separately. Plouaré is pronounced Plu-ar-ay; it is a suburb of
Defects in the Human Leukocyte Antigen Class I Antigen Processing Machinery in Head and Neck Squamous Cell Carcinoma: Association with Clinical Outcome
Authors: Markus Meissner, Torsten E. Reichert, Martin Kunkel, William Gooding, Theresa L. Whiteside, Soldano Ferrone, Barbara Seliger
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Human leukocyte antigen (HLA) class I antigen defects, which are frequently present in head and neck squamous cell carcinoma (HNSCC) cells may provide the tumor with an escape mechanism from immune surveillance. Scanty information is available about mechanisms underlying HLA class I antigen defects in both lesions and cell lines from HNSCC. In this study, we investigate the role of antigen processing machinery (APM) component abnormalities in the generation of deficient HLA class I surface expression of HNSCC cells. Experimental Design: Using immunohistochemistry, Western blot, and RT-PCR analyses we correlated the expression of the IFN-γ inducible proteasome subunits and of the peptide transporter TAP with that of HLA class I antigens in biopsies and cell lines from primary, recurrent, and metastatic HNSCC. Furthermore, APM component and HLA class I antigen expression in surgically removed lesions were correlated with the course of the disease in order to assess the clinical significance of deficient expression of these molecules. Results: A high frequency of LMP2, LMP7, and TAP1 down-regulation or loss was found in tumor lesions and cell lines obtained from HNSCC cancer patients. These defects could be corrected by incubating cells with IFN-γ. Furthermore, LMP2, LMP7, TAP1, TAP2, and HLA class I antigen expression rates in primary HNSCC lesions were found to predict overall survival. Lastly, the level of LMP7 expression was significantly associated with disease recurrence at 2 years. Conclusions: Our results suggest that the analysis of APM component expression in HNSCC lesions can provide useful prognostic information in patients with HNSCC.
Temporal Aspects of Occupational Bladder Carcinogenesis
Authors: Robert Hoover, Philip Cole
Journal: New England Journal of Medicine (1973)

Temporal aspects of occupationally induced bladder cancer were estimated with data from a case–control study in eastern Massachusetts. A total incidence series of men with bladder cancer were the cases, and an age-matched sample of men selected at random from the general population were the controls. The younger a man is when he begins employment in a hazardous occupation, the higher his risk of bladder cancer. Men first employed in a hazardous occupation by the age of 25 have a risk 2.4 times that of men never so employed. Virtually no excess risk is apparent for men first employed in such occupations after the age of 25. Risk of occupational bladder cancer is greatest 41 to 50 years after beginning employment in a hazardous occupation, the "latent period." There is no change in risk with increasing duration of employment in such occupations. However, it appears that increased duration of employment in a hazardous occupation is associated with a shortened latent period. (N Engl J Med 288:1040–1043, 1973)
Use of Intravascular Ultrasound to Compare Effects of Different Strategies of Lipid-Lowering Therapy on Plaque Volume and Composition in Patients With Coronary Artery Disease
Authors: Michael Schartl, Wolfgang Bocksch, Dietmar H. Koschyk, Wolfram Voelker, Karl R. Karsch, Jörg Kreuzer, Dirk Hausmann, Stephan Beckmann, Michael Gross
Journal: Circulation (2001)

We studied whether lipid-lowering therapy with atorvastatin (target LDL cholesterol [LDL-C] <100 mg/dL) compared with a moderate treatment regimen that used other lipid-lowering drugs led to a lesser progression of atherosclerosis and to different changes in plaque echogenicity in patients with coronary artery disease.This study was a 12-month, open-label, randomized, multicenter trial, which used serial 3D intracoronary ultrasound to calculate plaque volume and plaque echogenicity. After transcatheter therapy, 131 patients were randomized (atorvastatin n=65, usual care n=66). The target plaque had to be a minor lesion (ie, a diameter stenosis of <50% on angiography). After 12 months, mean LDL-C was reduced from 155 to 86 mg/dL in the atorvastatin group and from 166 to 140 mg/dL in the usual care group. Mean absolute plaque volume showed a larger increase in the usual care group compared with the atorvastatin group (usual care 9.6+/-28.1 mm(3), atorvastatin 1.2+/-30.4 mm(3); P=0.191). The hyperechogenicity index of the plaque increased to a larger extent for the atorvastatin group than for the usual care group, with a significant treatment effect for the percent change (atorvastatin 42.2%, usual care 10.1%; P=0.021).One year of lipid-lowering therapy to <100 mg/dL LDL-C most likely led to a slowdown of plaque growth of minor lesions. The significantly larger increase in plaque hyperechogenicity is most likely due to a change in plaque composition.