tbuckley/cabot-search huggingface dataset:
Clearance of the original hepatitis B virus YMDD-motif mutants with emergence of distinct lamivudine-resistant mutants during prolonged lamivudine therapy
Authors: Chau-Ting Yeh, Rong-Nan Chien, Chia-Ming Chu, Yun-Fan Liaw
Journal: Hepatology (2000)

Tyrosine-methionine-aspartate-aspartate (YMDD)-motif mutants may emerge and elicit immune clearance during prolonged lamivudine treatment. The aim of this study was to investigate the virological events following development of the original mutants. Twenty-three patients who developed YMDD-motif mutants during the Asian lamivudine trial were included. Serial serum samples from these patients were subjected to sequence analysis to identify new mutants. Site-directed mutagenesis experiments were performed to investigate whether the new mutations were responsible for lamivudine resistance. Of the 23 patients included, 13 harbored either one or a mixture of the two common YMDD-motif mutants (methionine 552-to-isoleucine [M552I] and leucine 528-to-methionine/methionine 552-to-valine [L528M/M552V]) throughout the course, whereas in the remaining 10 patients, distinct mutants became dominant over the original mutants to cause continuing chronic hepatitis. Of them, 3 developed an alanine 529-to-threonine (A529T) mutant, 6 developed a leucine 528-to-methionine/methionine 552-to-isoleucine (L528M/M552I) mutant, and 1 developed these two mutants sequentially. Site-directed mutagenesis experiments confirmed that the aforementioned mutations were responsible for the resistance to lamivudine in vitro. The nucleotide substitution in the A529T mutant concomitantly generated a stop codon at the surface gene, leading to impaired secretion of HBsAg. Strikingly, the replication of this mutant was lamivudine dependent. These results suggested that distinct lamivudine-resistant mutants could emerge and replace the original YMDD-motif mutants as the cause of continuing chronic hepatitis during prolonged lamivudine therapy.
Effect of chronic subcutaneous or intramural administration of heparin on femoral artery restenosis after balloon angioplasty in hypercholesterolemic rabbits. A quantitative angiographic and histopathological study.
Authors: L W Gimple, S D Gertz, H L Haber, M Ragosta, E R Powers, W C Roberts, I J Sarembock
Journal: Circulation (1992)

BACKGROUND Heparin is known to have antithrombotic, anticoagulant, and antiproliferative effects. We hypothesized that chronic subcutaneous and/or direct intramural administration of heparin would reduce restenosis and inhibit plaque growth after balloon angioplasty. METHODS AND RESULTS Focal atherosclerosis was induced bilaterally in the femoral arteries of 59 rabbits by air desiccation intimal injury and a 2% cholesterol diet. After angioplasty, the rabbits were assigned to one of four treatment groups. Control arteries (n = 21) received no additional heparin. A second group of 20 arteries was treated with a porous balloon that delivered heparin (1,500 units) directly into the arterial wall. A third group (n = 29) received subcutaneous heparin (350 units.kg-1.day-1) for 28 days, and a fourth group (n = 23) was treated with subcutaneous and intramural heparin. Quantitative angiography showed a modest reduction in restenosis (defined as the change in minimal luminal diameter from immediately after angioplasty to 28 days) with subcutaneous heparin compared with control arteries (0.32 +/- 0.18 versus 0.58 +/- 0.34 mm, p &lt; 0.01); however, luminal diameter was not improved at 28 days compared with before angioplasty. Intramural delivery of heparin by the porous balloon catheter was confirmed by use of fluoresceinated heparin in one animal. Angiographic restenosis was not reduced in arteries treated with intramural heparin versus controls (0.61 +/- 0.54 versus 0.58 +/- 0.34 mm, p = NS). Blinded planimetric analysis of histological sections showed no differences in luminal cross-sectional area narrowing by atherosclerotic plaque, in plaque area, or in plaque/media ratio at 28 days among the four treatment groups. CONCLUSIONS Chronic subcutaneous heparin after balloon angioplasty results in a modest reduction in angiographic restenosis in this model; however, the absolute luminal diameter is not improved compared with before angioplasty, and plaque area and percent luminal narrowing by plaque were not different among the four treatment groups. Heparin can be delivered into an atherosclerotic plaque by a porous balloon, but this treatment does not reduce restenosis after angioplasty in this model.
Increased Adventitial Mast Cells in a Patient with Coronary Spasm
Authors: Mervyn B. Forman, John A. Oates, David Robertson, Rose Marie Robertson, L. Jackson Roberts, Renu Virmani
Journal: New England Journal of Medicine (1985)

ALTHOUGH coronary spasm is an important component of a number of ischemic cardiac syndromes,1 2 3 4 5 6 its cause or causes remain ill-defined. Numerous hypotheses have been considered to explain the mechanisms producing focal vascular hyperreactivity. Our investigations of the autonomic nervous system, and both measurement of thromboxane A2 metabolites and treatment with potent cyclooxygenase inhibitors failed to support the role of thromboxanes in the pathogenesis of coronary spasm.7 8 9 10 Accordingly, we studied the possibility that cellular infiltration of the vessel wall could be a source of vasoconstrictor factors,11 and have now examined coronary vessels in a patient with well-characterized coronary spasm and . . .
Four Cases of Laparotomy for Intussusception
Authors: K. Monsarrat
Journal: BMJ (1900)

LAPAROTOMY FOR INTUSSUSOEPTION.r[ANDZCALJOURNA 1431 vesicle, but more probably it was, in part at least, a spurious capsule formed from the surrounding tissues by irritation.Remark8 by Mr. Wright.-Thehistory, the physical signs, the result of tapping and probabilities all led us to think that the tumour in this case was very probably renal or perirenal in origin.It was fully recognised that the operation was a forlorn hope, but it was the only chance.As is so often the case in abdominal tumours, when once the operation is begun it is impossible to stop short.Lacerated soft friable tissue may make partial removal or abandonment of an operation impossible on account of bleeding.The only thing to do is to clear away the whole mass as quickly as possible.In this operation it was recognised fairly early that we had a tera- toma to deal with, and that its attachments were such as to make its removal almost hopeless, but it was still the only chance.It is of course very unlikely that another similar case will be met with by any of those who saw this child, but it is worth recording, and the possibility of such a case is worth bearing in mind in doubtful congenital tumours.We are greatly indebted to Drs.Ballantyne and Fothergill for the care and trouble they have taken in examining and drawing the specimen.
Reply to Dr. Paquin.
Authors: DeLancey Rochester
Journal: JAMA (1897)

Buffalo, N. Y., Aug. 26, 1897. <h3>To the Editor:</h3> —I desire a little space to reply to an article of Dr. Paul Paquin written in criticism of my report, on treatment of tuberculosis, presented at the last meeting of theAmerican Medical Association. Far from belittling the results of serum-therapy and declaring against the use of tubercle antitoxin, I am heartily in favor of such methods of treatment in suitable cases. The conclusions to which I came in regard to antitoxin are, it seems to me, thoroughly justified and are not materially different from Dr. Paquin's own conclusions: viz., that "in cases of phthisis that are at all advanced it is of no value, that in the<i>one</i>case (and I particularly state<i>one</i>) of almost pure tuberculosis of larynx and upper lobe in which I used it, it was worse than useless, not having stayed the disease and having
Contraindictions to smallpox vaccination.
Authors: J A Dudgeon
Journal: BMJ (1973)

Acute tubular necrosis 2012{7 dense 4 4 7Subacute glomerular or vascular disease 5 2 faint 1 2 1 hypertension in one); only one of these patients recovered some renal function.Urography was performed during the first two weeks of acute renal failure, always before the onset of the recovery phase, 140 ml of methylglucamine iothalamate (Contrix 28; 28% iodine) (being given in a single injection lasting less than five minutes.Plain films and tomograms were taken before and up to 24 hours after the injection of the contrast medium.The findings are sum- marized in the table.In the 20 cases of acute tubular necrosis it may *be seen that, contrary to the experience of Dr. Cattell and his oolleagues, we found no evidence of a nephrogram in four cases and a delayed nephrogram in four others.Nevertheless, all
Plasma Propranolol Levels in the Quantitative Assessment of -adrenergic Blockade in Man
Authors: D. J. Coltart, D. G. Shand
Journal: BMJ (1970)

Plasma propranolol levels associated with reductions in endogenous and exogenous cardiac beta-stimulation were determined in normal people. The levels associated with a given degree of blockade of exercise-induced tachycardia were about three times greater after intravenous administration than after oral administration. This shows that an active metabolite of propranolol is formed only after the drug is taken by mouth. The greatest reduction in the tachycardia of strenuous exercise was associated with plasma levels of 40 ng./ml. with oral administration and 100 ng./ml. with intravenously administered propranolol.The effect on isoprenaline-induced tachycardia following intravenously administered propranolol showed that the dose ratio for isoprenaline was about 30 with plasma levels of 100 ng./ml. and 10 with levels of 10-20 ng./ml. These plasma levels give 100% and 20-30% blockade of exercise-induced tachycardia. These findings suggest that some of the therapeutic effects of propranolol may be unrelated to beta-adrenergic blockade.
Sweet's syndrome associated with sargramostim (granulocyte‐macrophage colony stimulating factor) treatment
Authors: Geetika Kumar, Jack M. Bernstein, Jill S. Waibel, Michael A. Baumann
Journal: American Journal of Hematology (2004)

Abstract Sweet's syndrome is an acute febrile neutrophilic dermatosis that is a known complication of the administration of filgrastim, a drug that causes increased neutrophil proliferation and differentiation. This complication has not previously been reported during treatment with sargramostim, a hematopoietic cytokine with activity that overlaps filgrastim. We report a case of Sweet's syndrome in association with sargramostim treatment following chemotherapy for acute myelogenous leukemia. A suspected second episode occurred after subsequent chemotherapy and sargramostim treatment. Physicians should be aware of this possible association because the signs and symptoms of Sweet's syndrome are easily mistaken as being due to infection. Am. J. Hematol. 76:283–285, 2004. © 2004 Wiley‐Liss, Inc.
Propranolol and Oxygen-Hemoglobin Equilibrium
Authors: MARSHALL A. LICHTMAN, JULES COHEN
Journal: Circulation (1974)

EDITORwe have attempted to discover new and better an- tiarrhythmic drugs by testing drugs with known neurodepressant effects against experimentally induced arrhythmias.4We have found that chlordiazepoxide is effec- tive in the treatment of ventricular arrhythmias induced by either digitalis or coronary occlusion.Chlordiazepoxide in combination with the peripherally-acting antiarrhythmic agent, lidocaine, is able to enhance the effect of lidocaine on arrhythmias evoked by coronary occlusion.4Attacking the "-neurophysiologic trigger" with drugs has also been reported by Nixon and colleagues in patients.5They suggested that prophylactic use of sleep therapy (i.e.pethidine plus promethazine) reduces mortality from acute myocardial infarction.Most methods for finding new antiarrhythmic drugs have been based on the idea that drugs must act directly on myocardial cell membranes to exert an antiarrhythmic effect.The failure of studies on isolated tissues to lead to promising new drugs may be due to the fact that the causative factors of arrhythmias occurring in vivo are missing in these preparations.Based on the data cited above plus the data of Lown and colleagues showing that sleep will sup- press ventricular premature beats, we feel that consideration of the nervous system may provide the basic understanding for discovering safe and effective new antiarrhythmic drugs.
RETRACTED: Tumor Dependence on the EGFR Signaling Pathway Expressed by the p-EGFR:p-AKT Ratio Predicts Erlotinib Sensitivity in Human Non-small Cell Lung Cancer (NSCLC) Cells Expressing Wild-Type EGFR Gene
Authors: Tianhong Li, Yi-He Ling, Roman Perez-Soler
Journal: Journal of Thoracic Oncology (2008)
Regulation of cyclin-dependent kinase inhibitor p21WAF1/Cip1/Sdi1 gene expression in hepatic regeneration
Authors: J H Albrecht, A H Meyer, M Y Hu
Journal: Hepatology (1997)

WAF1/Cip1/Sdi1 (p21) is the prototype of a family of proteins that inhibit cyclin–dependent kinases and regulate cell cycle progression in eukaryotic cells. In addition to normal cell cycle progression, p21 is involved in growth suppression mediated by p53 and transforming growth factor β (TGFβ), differentiation, and apoptosis. To gain insight into the possible involvement of p21 in liver cell growth, the expression and regulation of the p21 gene was evaluated in rodent models of liver regeneration and specimens of human liver diseases. Little p21 mRNA was detected in normal liver tissue. After growth stimulation in vivo by 70% partial hepatectomy (PH), the p21 transcript was upregulated in a biphasic manner, with enhanced expression during G1 phase and following S phase. The induction of p21 after PH was regulated primarily at the post–transcriptional level and was due to enhanced mRNA stability. Inhibition of protein synthesis with cycloheximide rapidly induced p21 expression, primarily by post–transcriptional stabilization of the transcript. Hepatic p21 mRNA was also induced by dietary protein deprivation in normal mice. Expression of the p21 gene after PH was similar in p53–deficient (p53 –/–) and wild–type mice, but was p53–dependent following protein deprivation. Primary hepatocytes in culture demonstrated increased p21 expression after treatment with hepatocyte growth factor, TGFβ, and activin A. p21 mRNA was upregulated in human liver diseases, suggesting a possible role in hepatic growth regulation in pathologic states. The present study demonstrates that p21 is regulated by p53–dependent and –independent pathways in the liver, and is influenced by both mitogenic and growth inhibitory stimuli.
Overdiagnosis and mistreatment of malaria among febrile patients at primary healthcare level in Afghanistan: observational study
Authors: T. Leslie, A. Mikhail, I. Mayan, M. Anwar, S. Bakhtash, M. Nader, C. Chandler, C. J. M. Whitty, M. Rowland
Journal: BMJ (2012)

<b>Objective</b> To assess the accuracy of malaria diagnosis and treatment at primary level clinics in Afghanistan. <b>Design</b> Prospective observational study. <b>Setting</b> 22 clinics in two Afghan provinces, one in the north (adjoining Tajikistan) and one in the east (adjoining Pakistan); areas with seasonal transmission of <i>Plasmodium vivax</i> and <i>Plasmodium falciparum</i>. <b>Participants</b> 2357 patients of all ages enrolled if clinicians suspected malaria. <b>Interventions</b> Established (&gt;5 years) microscopy (12 clinics in east Afghanistan), newly established microscopy (five clinics in north Afghanistan), and no laboratory (five clinics in north Afghanistan). All clinics used the national malaria treatment guidelines. <b>Main outcome measures</b> Proportion of patients positive and negative for malaria who received a malaria drug; sensitivity and specificity of clinic based diagnosis; prescriber’s response to the result of the clinic slide; and proportion of patients positive and negative for malaria who were prescribed antibiotics. Outcomes were measured against a double read reference blood slide. <b>Results</b> In health centres using clinical diagnosis, although 413 of 414 patients were negative by the reference slide, 412 (99%) received a malaria drug and 47 (11%) received an antibiotic. In clinics using new microscopy, 37% (75/202) of patients who were negative by the reference slide received a malaria drug and 60% (103/202) received an antibiotic. In clinics using established microscopy, 50.8% (645/1269) of patients who were negative by the reference slide received a malaria drug and 27.0% (342/1269) received an antibiotic. Among the patients who tested positive for malaria, 94% (443/472) correctly received a malaria drug but only 1 of 6 cases of falciparum malaria was detected and appropriately treated. The specificity of established and new microscopy was 72.9% and 79.9%, respectively. In response to negative clinic slide results, malaria drugs were prescribed to 270/905 (28.8%) and 32/154 (21%) and antibiotics to 347/930 (37.3%) and 99/154 (64%) patients in established and new microscopy arms, respectively. Nurses were less likely to misprescribe than doctors. <b>Conclusions</b> Despite a much lower incidence of malaria in Afghanistan than in Africa, fever was substantially misdiagnosed as malaria in this south Asian setting. Inaccuracy was attributable to false positive laboratory diagnoses of malaria and the clinicians’ disregard of negative slide results. Rare but potentially fatal cases of falciparum malaria were not detected, emphasising the potential role of rapid diagnostic tests. Microscopy increased the proportion of patients treated with antibiotics producing a trade-off between overtreatment with malaria drugs and probable overtreatment with antibiotics.
Notes of Experiences in Egypt
Authors: W. H. Flower
Journal: BMJ (1874)

CAIRO, the capital of Egypt, is one hundred and thirty miles from Alexandria.It is reached by railway in four-and-a-half hours by ex- press, and in six hours by ordinary trains.Refreshments can be obtained, if necessary, at Kafr ez Zyat station, about half way.The line runs the i whole distance through the delta, a low-lying, level, green, fertile, i populous land, intersected by numerous canals and branches of the great river.To strangers, it is full of interest the whole way, the buildings, the people, the animals, the vegetation, the agriculture, all different from anything seen before; and then, shortly before reaching Cairo, a distant glimpse is obtained of the stately group of pyramids of Ghizeh, I which, the more they are studied and compared with other and later I works of man, the more are found to merit the ancient appellation of 1."wonders of the world".Not many years ago, Masr el Kahirah (Masr the Victorious) of the Arabs, Le Caire of the French, Grand Cairo of early English travellers was in every aspect one of the most picturesque and oriental of cities. Owing to its vast size and the natural conservatism of the worshippers of Islam, great portions of the city still retain their ancient character, and it is still possible to lose oneself in mazes of narrow crooked streets vwhere no vestige can be seen of any alteration in manner, custom, or appearance of the inhabitants or their dwellings since the golden days of Haroun Al'Raschid.But other parts of the city, especially those wrhich are first seen by the traveller arriving at the station and driving to one of the principal hotels, savour more of modern France or Italy than of the Arabian Nights.Here we meet with wide well watered boulevards, shaded with straight rows of acacia trees, and lighted with gas, bordered with detached villas in neatly kept gardens ; hlandsome colonnaded streets with shops that might vie with those of the Palais
Lipid Disorders in Diabetes
Authors: Ronald B Goldberg
Journal: Diabetes Care (1981)

Hyperlipidemia is common in diabetic patients. While our understanding of lipid and lipoprotein metabolism in diabetes is incomplete, a pathophysiologic approach to this problem is presented. It is based on the recognition that diabetes is metabolically heterogeneous. Thus the roles of insulin deficiency, insulin resistance, obesity, and genetic factors are discussed in relation to their effects on lipoprotein production and catabolism. The most important defect in insulin-deficient subjects appears to be a deficiency of lipoprotein lipase, which is responsible for the removal of the triglyceride-rich lipoproteins. In non-insulin-dependent subjects there is evidence for a removal defect as well as, in some patients, for overproduction of VLDL-triglyceride. Cholesterol levels may be elevated and it is important to distinguish between VLDL, LDL, and HDL as the causes for these increases. HDL-cholesterol levels may be increased in insulin-dependent subjects, whereas they may be decreased in obese non-insulin-dependent patients. Mild elevations of LDL-cholesterol may occur in inadequately controlled type I and II diabetic patients, while elevated VLDL may raise the serum cholesterol in addition to the triglyceride levels. The rationale for therapy is based on the complications of severe hypertriglyceridemia and the risk of occlusive atherosclerosis. Management is directed at improving glycemic control, altering dietary composition, and reducing calories in obese patients. Improved glycemic control is effective in reducing triglyceride and cholesterol levels in insulin-deficient subjects. The response of the non-insulin-dependent diabetic patient to improved control may be complicated by associated obesity or familial hyperlipidemia. The advantages and disadvantages of fat versus carbohydrate restriction in the diet are discussed. Finally, resistant hyperlipidemia may require drug therapy. Diabetic hyperlipidemia should be viewed as resulting from an interaction between the diabetic syndrome, the genetic background of the patient, and the environment.
Plasma theophylline concentrations, six minute walking distances, and breathlessness in patients with chronic airflow obstruction
Authors: A C Davidson, C B Cooper
Journal: BMJ (1985)

Plasma theophylline concentrations, six minute walking distances, and breathlessness in patients with chronic airflow obstruction SIR,-While no one would argue that the in- discriminate use of any drug in any condition is unjustifiable, we have serious doubts about the value of Dr W V Evans's study of theophylline in chronic bronchitis (15 December, p 1649).We supplied theophylline and placebo to Dr Evans but were given no opportunity to dis- cuss his findings with him before publication.We do, however, possess the raw data.Our criticisms are as follows.Firstly, patients who had greater than 20%,' improvement in peak expiratory flow rate (PEFR) or forced expiratory volume in one second (FEV1) with 32 agonists were excluded from his study.Addis et al, using the Medical Research Council clinical criteria for chronic bronchitis, found a maximal response to salbutamol of 58V, in PEFR, 28% in FEV1, and 480,o in forced vital capacity (FVC), the last in their opinion being the most sensitive index of response.'Furthermore, they found that the response in FVC to theophylline
An alternative to colostomy.
Authors: N R Parrott, H B Devlin
Journal: BMJ (1979)

1979diagnosis, or both.The biochemist then decides what tests, if any, will help.Moreover, no report would leave the department without an expert interpretation of the result.To implement such a proposal would require a drastic change in the philosophy of both clinicians and biochemists; but it is, of course, the only logical solution.