tbuckley/cabot-search huggingface dataset:
Isoniazid-Induced Carbamazepine Toxicity and Vice Versa
Authors: James M. Wright, Elaine F. Stokes, Vincent P. Sweeney
Journal: New England Journal of Medicine (1982)

When isoniazid, a drug used in the treatment of tuberculosis, is given to patients receiving phenytoin, phenytoin intoxication develops in some patients with the slow-acetylator phenotype.1 This interaction is presumably a result of isoniazid's ability to inhibit liver microsomal p-hydroxylation, the major route of inactivation of phenytoin.The most serious adverse effect of isoniazid, hepatotoxicity, is thought to result from microsomal metabolism of the metabolite, acetylhydrazine, to a reactive intermediate.2 Carbamazepine is an antiepileptic drug that is eliminated by microsomal metabolism in the liver. It is a microsomal-enzyme-inducing agent, and it induces its own metabolism.3 Carbamazepine intoxication has been . . .
Mitomycin C: An Alternative Conservative Treatment for Refractory Esophageal Stricture in Children?
Authors: S. Uhlen, P. Fayoux, F. Vachin, D. Guimber, F. Gottrand, D. Turck, L. Michaud
Journal: Endoscopy (2006)

Background and Study Aims: Mitomycin C is an antiproliferative agent that has been used successfully as an adjunct treatment in ophthalmological procedures, in the management of laryngeal and tracheal stenosis, and more recently to prevent the recurrence of caustic esophageal strictures in children. The aim of this study was to assess the efficacy and safety of local application of mitomycin C to refractory esophageal strictures in children. Patients and Methods: We performed a preliminary prospective study of local application of mitomycin C in four children, aged between 1 year and 6 years, who had refractory esophageal strictures. Two of the children presented with strictures caused by caustic ingestion and the other two children had anastomotic strictures following surgical repair of congenital esophageal atresia. The patients had required between four and ten esophageal dilations over a 5 - 24-month period before mitomycin C application. After an endoscopic dilation, mitomycin C was applied onto the dilation wound using a rigid endoscope. Results: No complications were observed after the procedure. One child required a second application of mitomycin C 2 weeks after the first application because of recurrence of dysphagia. All the children remained asymptomatic and none of them required further dilation over a mean follow-up period of 24 months. Radiological control examinations revealed that there was no recurrence of the esophageal strictures and esophageal biopsies performed during follow-up showed no signs of dysplasia. Conclusions: Local application of mitomycin C is a potential alternative to iterative dilations, surgery, or stent placement for the treatment of refractory esophageal strictures in children. However, prospective, long-term assessment of outcomes is needed before any definitive conclusion can be drawn about the usefulness of mitomycin C in these patients.
Study shows which children at greatest risk of cerebral oedema in diabetic crisis
Authors: D. Spurgeon
Journal: BMJ (2001)

Giving bicarbonate to children in diabetic crisis seems to increase the risk of cerebral oedema, which can be fatal, a study in the New England Journal of Medicine has reported (2001;344:264-9). It should therefore be avoided in most cases, it added.

The study identified two simple blood test measurements that can help to predict which patients are in serious danger of developing cerebral oedema. It is the largest and most statistically rigorous examination of risk factors for the condition in children with diabetic ketoacidosis, …
Gene Transfer of Redox Factor-1 Inhibits Neointimal Formation
Authors: Hwan Myung Lee, Byeong Hwa Jeon, Kyung-Jong Won, Chang-Kwon Lee, Tae-Kyu Park, Wahn Soo Choi, Young Min Bae, Hyo Shin Kim, Sang Ki Lee, Seung Hwa Park, Kaikobad Irani, Bokyung Kim
Journal: Circulation Research (2008)

The role of apurinic/apyrimidinic endonuclease-1/redox factor-1 (Ref-1) in vascular smooth muscle cells has yet to be clearly elucidated. Therefore, we attempted to determine the roles of Ref-1 in the migration induced by platelet-derived growth factor (PDGF)-BB and in its signaling in rat aortic smooth muscle cells (RASMCs). Cellular migration, superoxide (O 2 −· ) production, Rac-1 activity, and neointima formation were determined in cells transfected with adenoviruses encoding for Ref-1 (AdRef-1) and small interference RNA of Ref-1. Overexpression of Ref-1 induced by treatment with RASMCs coupled with AdRef-1 inhibited the migration induced by PDGF-BB. PDGF-BB also increased the phosphorylation of the PDGFβ receptor, spleen tyrosine kinase (Syk), mitogen-activated protein kinase, and heat shock protein 27, but these increases were significantly inhibited by AdRef-1 treatment. PDGF-BB increased O 2 −· production and Rac-1 activity, and these were diminished in cells transfected with AdRef-1. In contrast, RASMC migration, phosphorylation of Syk and O 2 −· production in response to PDGF-BB were increased by the knock down of Ref-1 with small interference RNA. The phosphorylation of PDGFβ receptor in response to PDGF-BB was inhibited completely by the Syk inhibitor and was partly attenuated by a NADPH oxidase inhibitor. PDGF-BB increased the sprout outgrowth of the aortic ring ex vivo, which was inhibited in the AdRef-1–infected RASMCs as compared with the controls. Balloon injury–induced neointimal formation was significantly attenuated by the gene transfer of AdRef-1. These results indicate that Ref-1 inhibits the PDGF-mediated migration signal via the inhibition of reactive oxygen species–mediated Syk activity in RASMCs.
798-2 Differential Sensitivity of AV and VA Conduction to Adenosine in Humans
Authors: Wen-Ter Lai, Sheng-Nan Wu, Chee-Siong Lee, Jung-Chou Wu, Sheng-Shiung Sheu, Yeo-Shin Hwang, Luiz Belardinelli
Journal: Journal of the American College of Cardiology (1995)
Growth Hormone Therapy and the Short End of the Stick
Authors: Melvin M. Grumbach
Journal: New England Journal of Medicine (1988)

Until recently, the criteria for the selection of short children for treatment with human growth hormone were rigidly defined and straightforward. The supply of pituitary-derived growth hormone was limited, and its distribution was controlled by a national agency supported by the National Institutes of Health. Treatment was restricted to children with documented growth hormone deficiency, who had a growth rate under the 25th percentile for age and an arbitrary plasma growth hormone concentration ≤14 mU per liter (7 ng per milliliter) on at least two provocative tests (using arginine, insulin, levodopa, clonidine, or glucagon) or physiologic assessments (employing exercise or . . .
Iron overload and prolonged ingestion of iron supplements: Clinical features and mutation analysis of hemochromatosis‐associated genes in four cases
Authors: James C. Barton, Pauline L. Lee, Carol West, Sylvia S. Bottomley
Journal: American Journal of Hematology (2006)

Abstract We evaluated and treated four white adults (one man, three women) who had iron overload associated with daily ingestion of iron supplements for 7, 15, 35, and 61 years, respectively. We performed HFE mutation analysis to detect C282Y, H63D, and S65C in each patient; in two patients, HFE exons were sequenced. In two patients, direct sequencing was performed to detect coding region mutations of TFR 2 , HAMP , FPN 1 , HJV , and ALAS 2 . Patients 1–4 ingested ˜153, 547, 1,341, and 4,898 g of inorganic iron as supplements. Patient 1 had hemochromatosis, HFE C282Y homozygosity, and β‐thalassemia minor. Patient 2 had spherocytosis and no HFE coding region mutations. Patient 3 had no anemia, a normal HFE genotype, and no coding region mutations in HAMP , FPN 1 , HJV , or ALAS 2 ; she was heterozygous for the TFR 2 coding region mutation V583I (nt 1,747 G→A, exon 15). Patient 4 had no anemia and no coding region mutations in HFE , TFR 2 , HAMP , FPN 1 , HJV , or ALAS 2. Iron removed by phlebotomy was 32.4, 10.4, 15.2, and 4.0 g, respectively. There was a positive correlation of log 10 serum ferritin and the quantity of iron removed by phlebotomy ( P = 0.0371). Estimated absorption of iron from supplements in patients 1–4 was 20.9%, 1.9%, 1.1%, and 0.08%. We conclude that the clinical phenotypes and hemochromatosis genotypes of adults who develop iron overload after ingesting iron supplements over long periods are heterogeneous. Therapeutic phlebotomy is feasible and effective, and would prevent complications of iron overload. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Coronary Arteries in Fatal Acute Myocardial Infarction
Authors: WILLIAM C. ROBERTS
Journal: Circulation (1972)

The coronary arteries are diffusely involved by atherosclerotic plaques in fatal acute myocardial infarction (AMI). The degree of luminal narrowing may vary but plaques are present in practically every millimeter of extramural coronary artery. Usually the lumens of at least two of the three major coronary arteries are narrowed &gt; 75% by old plaques in patients who die suddenly (&lt; 6 hours) from cardiac disease with or without myocardial necrosis. Coronary thrombi occur in about 10% of patients who die suddenly or in whom necrosis is limited to the left ventricular subendocardium, and in about 50% of patients with transmural myocardial necrosis. Coronary thrombi usually indicate the presence of shock or congestive heart failure or both during the development of myocardial necrosis. The infrequency of coronary thrombi in patients dying suddenly of cardiac disease and in those with transmural necrosis who never have shock or congestive heart failure suggests that the thrombi may be consequences rather than causes of AMI. Although it may not precipitate AMI, coronary thrombosis may still be the underlying cause of the atherosclerosis. The finding of fibrin deposits in old atherosclerotic plaques and the findings of atherosclerotic-type lesions (cholesterol clefts, foam cells, pultaceous debris, calcific deposits) in organized known thrombi (as in the left atrium in mitral stenosis) suggest a strong relationship between thrombosis and atherosclerosis. Coronary arterial emboli are not rare; they are located in distal portions of the coronary tree and are present in the small epicardial branches as well as in intramural coronary arteries. In contrast, coronary thrombi are located in proximal portions of major extramural vessels, are infrequent in the small epicardial branches, and are absent in intramural coronary arteries. Coronary atherosclerosis is limited to the extramural coronary arteries and spares the intramural coronary arteries.
p -Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase
Authors: Hiroshi Watanabe, Yohei Miyamoto, Daisuke Honda, Hisae Tanaka, Qiong Wu, Masayuki Endo, Tsuyoshi Noguchi, Daisuke Kadowaki, Yu Ishima, Shunsuke Kotani, Makoto Nakajima, Keiichiro Kataoka, Shokei Kim-Mitsuyama, Motoko Tanaka, Masafumi Fukagawa, Masaki Otagiri, Toru Maruyama
Journal: Kidney International (2013)
Human models for in vivo and in vitro assessment of topical antifungal compounds
Authors: ARTHUR G. KNIGHT
Journal: British Journal of Dermatology (1973)

Topical antifungal agents, 1% haloprogin solution (Halotex®), 1% tolnaftate solution (Tinactin®), 1% sodium omadine cream and 5% thiabendazole in dimethylacetamide have been investigated. They were tested for prophylactic effect against experimental human Trichophyton mentagrophytes infections. All the drugs were totally effective against experimental infection if the inoculation was immediate. However, after 48 h the effects of haloprogin and tolnaftate were greatly reduced, but the others were still very effective. Statum corneum may be stripped onto a tape, sterilized and then inoculated with T.mentagrophytes spores. Under controlled conditions the spores germinate in vitro in the stratum corneum. This method has been quantitated and adapted to the investigation of topical antifungal agents. Results show that tolnaftate has very title antifungal activity even at zero time, thiabendazole and sodium omadine retain excellent activity in the stratum corneum for 48 h and are readily detectable even 72 h after one application.
Philosophy and practice of advance care planning in Scotland
Authors: C. M. Carolan
Journal: BMJ (2013)

I was disappointed that in their otherwise excellent review Mullick and colleagues failed to highlight important differences in advance care planning across the UK,1 notably differences in the assessment of capacity in Scotland and Northern Ireland. The UK has no central register of these plans, but no mention was made of Scotland’s nationwide electronic palliative care summary introduced in 2010. …
Characterization of autoantibodies against uridine-diphosphate glucuronosyltransferase in patients with inflammatory liver diseases
Authors: Thomas Bachrich, Therese Thalhammer, Walter Jäger, Petra Haslmayer, Belma Alihodzic, Silvia Bakos, Eva Hitchman, Adrian M. Senderowicz, Edward Penner
Journal: Hepatology (2001)

Uridine diphosphate glucuronosyltransferase (UGT) was identified as an antigenic target in a subgroup of liver–kidney microsomal autoantibodies and was termed LKM–3. To evaluate the nature of LKM–3 antibodies, we screened sera from 80 untreated patients with autoimmune hepatitis (AIH) type 1 and 2, primary biliary cirrhosis (PBC), AIH/PBC, hepatitis C virus (HCV) infection, and 12 healthy individuals (controls) against 7 recombinant human UGT isoenzymes (UGT1A1, UGT1A4, UGT1A6, UGT1A7, UGT1A9, UGT1A10, and UGT2B7). Autoantibodies reacting against various UGT isoenzymes were observed in sera from 3 of 18 AIH type 2 and 1 of 27 of the HCV patients. The anti–UGT-positive sera from AIH type 2 patients revealed the strongest immunoreactivity against UGT1A1, the main UGT–isoform involved in the bilirubin glucuronidation. Additionally, these sera were able to block UGT–mediated substrate glucuronidation in vitro . The prevalence for UGT1A1 was shown by 2 independent techniques: (1) UGT1A1 was identified as the main antigen by Western blotting. Preabsorption of sera with UGT1A1 prevented reaction against all tested UGT–isoforms. (2) In vitro immunoinhibition experiments showed that glucuronidation of the anticancer drug flavopiridol by UGT1A1 was more strongly inhibited than its UGT1A9–mediated biotransformation. In contrast, the serum from the HCV–patient reacted predominately with UGT1A6, and moreover, the immunoreactivity pattern was different from that of the AIH group. To summarize, we show the subtype preference of antibodies against UGT1A1 in a subgroup of AIH type 2 patients. These autoantibodies inhibit UGT–mediated glucuronidation in vitro , but it is unlikely that anti–UGT antibodies will have a marked effect on the patients capacity for drug biotransformation, as serum bilirubin levels in patients remained within the normal range.
Uncomplicated Acute Bronchitis
Authors: Ralph Gonzales
Journal: Annals of Internal Medicine (2000)

Acute bronchitis is an acute cough illness in otherwise healthy adults that usually lasts 1 to 3 weeks. This review describes the pathophysiology of the condition and provides a practical approach to the evaluation and treatment of adults with uncomplicated acute bronchitis. Practical points to be made are: 1. Respiratory viruses appear to cause the large majority of cases of uncomplicated acute bronchitis. 2. Pertussis infection is present in up to 10% to 20% of adults with cough illness of more than 2 to 3 weeks' duration. No clinical features distinguish pertussis from nonpertussis infection in adults who were immunized against pertussis as children. 3. Transient bronchial hyperresponsiveness appears to be the predominant mechanism of the bothersome cough of acute bronchitis. 4. Ruling out pneumonia is the primary objective in evaluating adults with acute cough illness in whom comorbid conditions and occult asthma are absent or unlikely. In the absence of abnormalities in vital signs (heart rate > 100 beats/min, respiratory rate > 24 breaths/min, and oral body temperature > 38 °C), the likelihood of pneumonia is very low. 5. Randomized, placebo-controlled trials do not support routine antibiotic treatment of uncomplicated acute bronchitis. 6. Randomized, placebo-controlled trials have shown that inhaled albuterol decreases the duration of cough in adults with uncomplicated acute bronchitis. 7. Intervention studies suggest that antibiotic treatment of acute bronchitis can be reduced by using a combination of patient and physician education. Decreased rates of antibiotic treatment are not associated with increased utilization, return visits, or dissatisfaction with care.
Early evidence of endothelial vasodilator dysfunction at coronary branch points.
Authors: J M McLenachan, J Vita, D R Fish, C B Treasure, D A Cox, P Ganz, A P Selwyn
Journal: Circulation (1990)

Intracoronary acetylcholine produces endothelium-dependent dilation of normal coronary arteries and paradoxical constriction of atherosclerotic vessels. Regional differences in endothelium-dependent vasomotion, however, have not been studied in relation to the nonuniform development of atherosclerosis. We compared the vasomotor response to increasing doses of acetylcholine of angiographically smooth coronary artery segments prone to atherosclerosis (coronary branch points) with segments remote from branch points (straight segments). In patients with entirely smooth coronary arteries and a dilator response to acetylcholine (group 1, n = 7), branch points and straight segments demonstrated equal and significant dose-dependent dilation to acetylcholine (14.7 +/- 8.9% and 12.3 +/- 12.7%, respectively; p identical to NS). In patients with early atherosclerosis as manifest by luminal coronary irregularities, the lowest dose of acetylcholine (10(-8) M) produced constriction at branch points and slight dilation at straight segments (-6.3 +/- 7.4% vs. +2.2 +/- 7.3%, p less than 0.05). At higher doses of acetylcholine, both branch point and straight segments constricted, but constriction remained more pronounced at branch points. Both branch point and straight segments, however, retained the ability to dilate to the non-endothelium-dependent agent, nitroglycerin. In a third group of patients with angiographically entirely smooth coronary arteries but without dilation to acetylcholine, constriction to acetylcholine again occurred first at branch points. Thus, coronary branch points demonstrate increased sensitivity to acetylcholine-induced constriction in patients with angiographic evidence of early coronary atherosclerosis and in middle-aged patients with smooth coronary arteries. These segments, however, retain the ability to dilate to nitroglycerin. Whether this early evidence of defective endothelium-dependent vasodilation predicts the later development of occlusive atherosclerosis is not yet known.
A Turning Point in Schizophrenia Genetics
Authors: Maria Karayiorgou, Joseph A Gogos
Journal: Neuron (1997)

Schizophrenia has been called "arguably the worst disease affecting mankind." The worldwide lifetime prevalence of the disorder is ∼1%. In 1990, the cost of caring for patients with schizophrenia in the United States was estimated to be $33 billion, accounting for ∼2.5% of total health care expenditures. The substantial funds being spent on the disease only reach a fraction of the affected population, since an estimated third to half of the homeless population, who never receive care, suffer from schizophrenia.
Drug treatment of hypertension
Authors: B. Williams
Journal: BMJ (2003)

Hypertension is one of the most important preventable causes of premature death worldwide,1 and the benefits of antihypertensive drugs have been confirmed by the largest evidence base from clinical trials in medicine. Many classes of drugs are available for treatment, and debate has raged about whether the benefits of treatment are purely a function of the quality of blood pressure control or whether the type of drug used might also be a powerful determinant of outcome. This is a key question because the difference in cost between “older” drugs (thiazides or β blockers) and “newer” drugs (such as angiotensin converting enzyme (ACE) inhibitors or calcium channel blockers) is substantial. A meta-analysis of trials of treatment for hypertension with the newer drugs found that ACE inhibitors and calcium channel blockers were likely to reduce cardiovascular morbidity and mortality by the same order of magnitude as β blockers or thiazides,2 but such analyses have insufficient statistical power to detect cause specific outcomes with regard to specific drugs.

Recently, the “antihypertensive and lipid lowering to prevent heart attack trial” (ALLHAT)—the largest ever randomised trial of antihypertensive treatment—reported its results.3 It was designed to determine whether the choice of first line treatment for hypertension influenced cardiovascular outcome. Importantly, the trial was sufficiently large to examine cause specific outcomes and was the first hypertension study to have sufficient power to examine the combined incidence of fatal coronary heart disease and non-fatal myocardial infarction as the primary end point.

ALLHAT was a randomised double blind controlled clinical trial conducted in 623 centres in North America. …
Mammalian phosphatidylinositol 4-kinases as modulators of membrane trafficking and lipid signaling networks
Authors: Emma L. Clayton, Shane Minogue, Mark G. Waugh
Journal: Progress in Lipid Research (2013)

The four mammalian phosphatidylinositol 4-kinases modulate inter-organelle lipid trafficking, phosphoinositide signalling and intracellular vesicle trafficking. In addition to catalytic domains required for the synthesis of PI4P, the phosphatidylinositol 4-kinases also contain isoform-specific structural motifs that mediate interactions with proteins such as AP-3 and the E3 ubiquitin ligase Itch, and such structural differences determine isoform-specific roles in membrane trafficking. Moreover, different permutations of phosphatidylinositol 4-kinase isozymes may be required for a single cellular function such as occurs during distinct stages of GPCR signalling and in Golgi to lysosome trafficking. Phosphatidylinositol 4-kinases have recently been implicated in human disease. Emerging paradigms include increased phosphatidylinositol 4-kinase expression in some cancers, impaired functioning associated with neurological pathologies, the subversion of PI4P trafficking functions in bacterial infection and the activation of lipid kinase activity in viral disease. We discuss how the diverse and sometimes overlapping functions of the phosphatidylinositol 4-kinases present challenges for the design of isoform-specific inhibitors in a therapeutic context.
THE PATHOLOGY OF EPIDEMIC CEREBROSPINAL MENINGITIS.
Authors: DANIEL N. EISENDRATH
Journal: JAMA (1899)

In 1887 Professor Weichselbaum<sup>1</sup>found a peculiar diplococcus which he called diplococcus intracellularis, in six cases of cerebrospinal meningitis, whose clinical histories corresponded exactly to that of the epidemic type of this disease, and not at all to that caused by the pneumococcus. He described these cocci as being particularly found within the cells of the exudate, always occuring in the form of a diplococcus with the opposite sides flattened. It grew best at body temperature, not well on blood or potato. Considerable confusion existed until 1895, when Jäger<sup>2</sup>published his observations in the cases of ten soldiers dying of the epidemic form of the disease. During this period, up to the time of Jäger's article, a number of articles appeared claiming that either all forms of meningitis were caused by the pneumococcus, and that this was but a localization of the general infection with this germ, or
ELR+ CXC chemokines and their receptors (CXC chemokine receptor 1 and CXC chemokine receptor 2) as new therapeutic targets
Authors: Cinzia Bizzarri, Andrea Rosario Beccari, Riccardo Bertini, Michela Rita Cavicchia, Simona Giorgini, Marcello Allegretti
Journal: Pharmacology & Therapeutics (2006)