tbuckley/cabot-search huggingface dataset:
Inhibition of the Proteasome Activity by Gallium(III) Complexes Contributes to Their Anti–Prostate Tumor Effects
Authors: Di Chen, Michael Frezza, Rajendra Shakya, Qiuzhi Cindy Cui, Vesna Milacic, Claudio N. Verani, Q. Ping Dou
Journal: Cancer Research (2007)

The investigation of metal-based complexes with potential antitumor activity has been of paramount importance in recent years due to the successful use of cisplatin against various cancers. Gallium(III) and subsequently developed gallium(III)-containing complexes have shown promising antineoplastic effects when tested in a host of malignancies, specifically in lymphomas and bladder cancer. However, the molecular mechanism responsible for their anticancer effect is yet to be fully understood. We report here for the first time that the proteasome is a molecular target for gallium complexes in a variety of prostate cancer cell lines and in human prostate cancer xenografts. We tested five gallium complexes (1-5) in which the gallium ion is bound to an NN'O asymmetrical ligand containing pyridine and substituted phenolate moieties in a 1:2 (M/L) ratio. We found that complex 5 showed superior proteasome inhibitory activity against both 26S proteasome (IC50, 17 micromol/L) and purified 20S (IC50, 16 micromol/L) proteasome. Consistently, this effect was associated with apoptosis induction in prostate cancer cells. Additionally, complex 5 was able to exert the same effect in vivo by inhibiting growth of PC-3 xenografts in mice (66%), which was associated with proteasome inhibition and apoptosis induction. Our results strongly suggest that gallium complexes, acting as potent proteasome inhibitors, have a great potential to be developed into novel anticancer drugs.
Reply to Fuccio and Cennamo
Authors: M. Bourke
Journal: Endoscopy (2010)

We thank Drs Fuccio and Cennamo for their interest in the cannulation paper. I agree that the recent data suggests that wire-guided cannulation (WGC) should now be the initial and preferred technique for conventional biliary cannulation. Two published meta-analyses, including the study by Cennamo and co-workers of the five randomized trials, confirm superior primary cannulation rates, decreased precut requirements and a significantly reduced risk of post-ERCP pancreatitis (PEP) [1] [2]. Thus, it seems that not only in theory, but also in practice, WGC for biliary cannulation is both safer and more effective.
Australia proposes peer review of alleged negligence cases
Authors: C. Zinn
Journal: BMJ (2002)

<h3>Abstract</h3> <h3>Summary statement</h3> This study describes for the first time long-lasting behavioral effects of hypoxia on a tropical fish, the white grunt (<i>Haemulon plumieri</i>) from Puerto Rico. Anthropogenic activities and climate change have resulted in an increase in hypoxia in nearshore ecosystems worldwide. The San Juan Bay Estuary System in Puerto Rico is one such ecosystem that has undergone an increase in hypoxic events over the past few years. We collected white grunts (<i>Haemulon plumieri</i>) from one of the estuary lagoons to study the effects of hypoxia on fast startle responses (fast-starts). We hypothesized that exposure to hypoxia would significantly decrease the frequency of fast-starts evoked by an abrupt sound stimulus. After an exposure to an oxygen concentration of 2.5 mg L<sup>-1</sup> (40% of air saturation), there is a significant reduction in the frequency of fast-starts that is maintained for at least 24 h after the exposure. Exposure to a random sequence of oxygen levels of 5.0, 4.3 and 3.7 mg L<sup>-1</sup> (80, 70, and 60% of air saturation) did not show a significant effect until one hour after exposure. We speculate that the lasting effect of hypoxia on fast-starts, thought to be involved in escape, will result in a greater susceptibility of the white grunt to predation. We have identified the Mauthner cell, known to initiate fast-starts, to allow future studies on how low oxygen levels impact a single cell and its circuit, the behavior it initiates and ultimately how changes in the behavior affect population and ecosystem levels.
Dysomia, Dysgeusia, and Diltiazem
Authors: JULIAN L. BERMAN
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 May 1985Dysomia, Dysgeusia, and DiltiazemJULIAN L. BERMAN, M.D.JULIAN L. BERMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-5-717_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Levinson and Kennedy (1) reported a case of dysomia and dysgeusia associated with nifedipine therapy. We report the case of a patient who developed dysgeusia and dysomia while taking diltiazem with subsequent slow spontaneous resolution of these symptoms.A 73-year-old man was first seen 2 years ago for stable angina pectoris. At that time he was treated with nifedipine, 20 mg four times a day, and nitroglycerin capsules (Nitro-Bid, Marion Laboratories, Incorporated, Kansas City, Missouri), 9 mg every 6 hours. A gastrointestinal disturbance required a change of therapy approximately 2 months later to diltiazem, 60 mg three...Reference1. LEVINSONKENNEDY JK. Dysomia, dysgeusia, and nifedipine. Ann Intern Med. 1985;102:135-6. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: JULIAN L. BERMAN, M.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byOlfactory Impairement in Disease and AgingAntiarrhythmic drug-induced smell and taste disturbancesSniffing out pharmacology: interactions of drugs with human olfactionAdverse drug reactions ? no farewell to harmsOlfactory Loss and Aging: An Ignored but Important RelationshipLoss of Taste, Smell, and Other Senses with AgeTaste and smell perception in the elderly: Effect of medications and diseaseMedication‐Induced Taste DisturbancesTroubles olfactifs d’origine médicamenteuse : analyse et revue de la littératureDisturbances of Taste and Smell Induced by DrugsDIAGNOSIS AND MANAGEMENT OF TASTE DISORDERS AND BURNING MOUTH SYNDROMEOlfaction in Aging and Medical DisordersDisorders in Taste and SmellProbleme bei der Behandlung mit KalziumantagonistenSide Effects — Overdosage — Contraindications — Drug InteractionsNebenwirkungen — Überdosierung (Vergiftung) — Kontraindikationen — ArzneimittelinteraktionenAntianginal and β-adrenoceptor antagonistsNifedipine and Myoclonic DystoniaALICIA DE MEDINA, M.D., OLIVIA BIASINI, M.D., ALFONSO RIVERA, M.D., ALICIA SAMPERA, M.D.Antianginal and β-adrenoceptor blocking drugs 1 May 1985Volume 102, Issue 5Page: 717-717KeywordsAngina ePublished: 1 December 2008 Issue Published: 1 May 1985 PDF downloadLoading ...
Acute aortic dissection
Authors: A. M. Ranasinghe, D. Strong, B. Boland, R. S. Bonser
Journal: BMJ (2011)

Acute aortic dissection is caused by an aortic intimal tear with propagation of a false channel in the media. Depending on the site and extent of the tear, it may cause chest, back, or abdominal pain, or collapse caused by rupture or malperfusion (transient or persistent ischaemia of any organ as a result of arterial branch obstruction). It is anatomically categorised according to involvement of the ascending aorta (type A, DeBakey type I/II) (fig 1⇓); the categorisation dictates management.



Fig 1 The two most common classifications of aortic dissection. The Stanford classification divides dissections into type A (involving the ascending aorta) and type B (no ascending involvement). The DeBakey classification subdivides Stanford type A into ascending and descending (type I) and ascending alone (type II). DeBakey type III is equivalent to Stanford type B. Stanford type A (DeBakey types I and II) dissection requires surgery, whereas most Stanford type B dissection is treated medically. DeBakey type I dissection has the greatest propensity for malperfusion. Neither classification reports the site of the intimal tear, and some dissections may propagate in a retrograde way. Adapted and reproduced with permission from Nienaber and Eagle1



#### Case scenario

A 64 year old hypertensive man presented to an emergency department with sudden onset, severe, sharp chest pain. Right arm blood pressure was 100/70 mm Hg and an electrocardiogram showed inferior ST segment depression. Troponin T was raised (0.2 ng/mL). Acute coronary syndrome was provisionally diagnosed, anti-platelet therapy administered, and coronary angiography planned. On later questioning, he described a left arm weakness that had resolved. Further examination noted left arm hypertension (155/90 mm Hg), a right carotid bruit, and diastolic murmur. Computed tomography showed a type A acute aortic dissection (see fig 2⇓) for an example from another case) involving the right coronary ostium and brachiocephalic …
Violence in America: time to bite the bullet back
Authors: P. H. Blackman
Journal: JAMA (1992)

To the Editor.  —It is ironic that with the editorial call by JAMA for registration and licensing for gun owners and their guns, 1 not one of over 70 articles, reprints, editorials, letters, reports, abstracts, book reviews, commentaries, or other communications in 10 American Medical Association (AMA) publications provided any data that treating guns like motor vehicles—for which registration and licensing are generally not required for possession and use exclusively on private property—would reduce firearms-related violence. Indeed, while editorially crediting registration and licensing for the recent reduction in motor vehicle accidents, the key article touching on that issue listed seven factors but not registration or licensing. 2 And undercutting the argument that public health initiatives reduced unintentional motor vehicle deaths and therefore can reduce intentional firearm deaths is the fact that the motor vehicle death rate declined less than that for other public accidents, work accidents, home accidents, or firearms
A MEMORABLE NON-PATIENT
Authors: D. Clark
Journal: BMJ (1995)

I'm normally bad at names. I remembered this one only because the letter sat for so long in my in tray. It explained that she was a teacher and had a friend with leukaemia. Could I answer a few questions about the disease? The letter ended with a hint of a donation, if I could also give her the address of a leukaemia charity.

The problem was the questions read like the final paper for the examination of the Royal College of Pathologists. Other letters and documents seemed more urgent and important. Three weeks passed and it was nearing the end of the summer term. I had begun to get …
Sodium and water balance in chronic congestive heart failure.
Authors: R J Cody, A B Covit, G L Schaer, J H Laragh, J E Sealey, J Feldschuh
Journal: Journal of Clinical Investigation (1986)

As the characteristics of sodium and water balance in heart failure remain undefined, we evaluated the hemodynamic, metabolic, and hormonal effects of balanced sodium intake in 10 patients with chronic congestive heart failure. We discontinued diuretics to avoid their confounding influence, and all patients received 1 wk of 10 meq and 100 meq balanced sodium intake and controlled free water. Comparing sodium intake of 10 with 100 meq, the following observations were made. There was weight gain (2.0 kg) and increased sodium excretion (11 +/- 3 to 63 +/- 15 meq/24 h), unaccompanied by increase of blood volume. Both renin-angiotensin system and sympathetic nervous system activity were greater during the 10 meq diet, and suppressed with the 100 meq sodium diet. For both diets, plasma renin and urinary aldosterone excretion were correlated with urinary sodium excretion (r = -0.768, r = -0.726, respectively; P less than 0.005). Systemic hemodynamics were minimally changed with increased sodium intake. However, reversal of vasoconstriction by captopril during the 10 meq diet, and its ineffectiveness during the 100 meq diet, indicated a renin-dependent mechanism in the former, and a renin-independent mechanism in the latter diet. There were two subgroups of response to the 100 meq diet: one group (n = 5) achieved neutral balance, while the second (n = 5) avidly retained sodium and water. Renin-angiotensin system activity was significantly higher in the latter group, and the mechanism for differences in sodium excretion for the subgroups could not be identified by blood volume or hemodynamic parameters. Orthostatic hypotension during tilt was greater during the 10 meq sodium diet, and in all cases, related to ineffective hemodynamic and hormonal compensatory responses.
Psychological Adaptation to Isolator Therapy in Acute Leukaemia
Authors: Alistair M. Gordon
Journal: Psychotherapy and Psychosomatics (1975)

Treatment under conditions of gnotobiotic isolation can augment the stress of adaptation to a diagnosis of leukaemia. Identification of the psychological problems experienced in isolator treatment can contribute to the effective maintenance of therapy. Individual patterns of adjustment to treatment relate to the psychological mechanisms of defence employed to contend with the dependent position enforced by isolation. Psychiatric assessment can assist both patients and nursing staff with the management of their separate difficulties in this unfamiliar treatment situation. Psychological features of isolator treatment in ten patients with acute leukaemia are described and suggestions proposed for psychological management of patients under isolator conditions.
Increase in fatal suicidal poisonings and suffocations in the year Final Exit was published: a national study
Authors: P M Marzuk, K Tardiff, A C Leon
Journal: American Journal of Psychiatry (1994)

Final Exit was a best-selling book that recommended poisoning and suffocation by plastic bag as lethal means of suicide for those with terminal medical illnesses. The authors sought to determine whether the number of suicides involving these methods increased in the United States in 1991, the year the book was published, compared with 1990. Suicidal asphyxiations involving a plastic bag increased 30.8%, from 334 to 437, and poisonings increased 5.4%, from 3,143 to 3,314. There was no change in the number of suicides involving each of the other methods or in the total number of suicides between 1990 and 1991. These ecological data support, but cannot conclusively prove, the hypothesis that Final Exit influenced the choice of lethal means of suicidal individuals.
Patient dies from novel coronavirus in UK
Authors: J. Wise
Journal: BMJ (2013)

A patient with the novel coronavirus has died at the Queen Elizabeth Hospital in Birmingham. 

The patient—who died on 17 February—was believed to belong to a family being treated for the condition in a Manchester hospital. Three cases in the United Kingdom have now occurred within the same family cluster, providing evidence of person to person transmission.1

The hospital disclosed that the patient who died was already an outpatient undergoing treatment for a long term, complex unrelated health condition, and was immunocompromised. 

There have now been 12 confirmed cases of the coronavirus worldwide, four of which have …
HAZARDS OF FIREWORKS ON CHRISTMAS AND NEW YEAR HOLIDAYS
Authors: Percy Bugbee
Journal: JAMA (1941)

<h3>To the Editor:—</h3> The American Medical Association has the gratitude of all who are laboring for adequate legislative control of fireworks. Your contribution in the form of the "Annual Survey of Fourth of July Accidents" is perhaps the most helpful and influential aid we have in bringing about the adoption of adequate state fireworks laws throughout the country. The survey does have, however, one important limitation which actually tends to make more difficult the efforts to extend fireworks laws in a large section of the country. This is simply that the survey covers only the period shortly before and after Independence Day, while, in the South, fireworks are used much more extensively in the celebration of Christmas and New Year's Day. The result is that any accounting of fireworks accidents resulting from Independence Day celebrations only places the Southern states in a very favorable position as compared to their northern
S3 Idiopathic Pulmonary Fibrosis, Mesothelioma, And Asbestosis Mortality Trends For England And Wales: Is Asbestos Exposure Associated With Ipf?
Authors: C. Reynolds, C. Barber, P. Cullinan
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Idiopathic pulmonary fibrosis (IPF) is more common in older people, in men, in manual workers, and in those living in more industrial areas of the country. It has been hypothesised that workplace asbestos exposure is an under-recognised cause of IPF. Studies of mesothelioma patients have shown that asbestos exposure is poorly recalled. If asbestos exposure is not known, asbestosis can be misclassified clinically as IPF because both can present with progressive breathlessness and radiological UIP. Our aim was to investigate a possible association between IPF and known asbestos-related mortality. Our objective was to visualise age-standardised annual mortality trends for IPF, mesothelioma, and asbestosis for men and women. <h3>Methods</h3> Age, sex, and region stratified mortality data for IPF, mesothelioma, and asbestosis were obtained for England and Wales from the Office of National Statistics for the period 1974–2012. Data were age-standardised and visualised using the Python Pandas data analysis library and matplotlib. <h3>Results</h3> The incidence of IPF continues to increase and is higher in men (male:female = 1:1.6) and in the north west of England. IPF and asbestos-related deaths are rare before the age of 40 and more common in elderly people. <h3>Conclusions</h3> New antifibrotic treatments for IPF throw into sharp focus the question of whether or not a proportion of IPF is due to occult asbestos exposure; patients known to have asbestos exposure are currently not considered to be candidates for antifibrotic treatments. Our data are consistent with a proportion of IPF being attributable to asbestos exposure but are not conclusive and further research is needed.
Interleukin‐8 inhalation directly provokes bronchoconstriction in guinea pigs
Authors: M Fujimura, S Myou, M Nomura, M Mizuguchi, T Matsuda, A Harada, N Mukaida, K Matsushima, A Harada, A Nonomura
Journal: Allergy (1999)

Background: Although it has been reported that the concentration of interleukin (IL)‐8 in nasal lavage fluid and sputum and its production in bronchial epithelium were increased in asthmatic subjects, the direct effects of IL‐8 on the airways in vivo is unclear. Methods: We examined bronchoconstriction in response to IL‐8 inhalation through an endotracheal cannula in anesthetized, artifically ventilated guinea pigs. Results: Inhalation of IL‐8 at concentrations of 1 and 10 μg/ml caused significant bronchoconstriction, as revealed by the elevation of pressure at the airway opening. Moreover, the bronchoconstriction induced by IL‐8 was significantly inhibited by the antihistamines diphenhydramine and terfenadine, suggesting the involvement of histamine release in the IL‐8‐induced bronchoconstriction. No significant leukocyte infiltration was observed in the bronchoalveolar lavage fluid or histologic findings 25 min after the first IL‐8 inhalation. Conclusions: IL‐8 provokes bronchoconstriction without leukocyte accumulation in the airways, mediated in part by histamine release, in guinea pigs.
High lipophilicity and high daily dose of oral medications are associated with significant risk for drug-induced liver injury
Authors: Minjun Chen, Jürgen Borlak, Weida Tong
Journal: Hepatology (2012)

Drug-induced liver injury (DILI) is a leading cause of drug failure in clinical trials and a major reason for drug withdrawals from the market. Although there is evidence that dosages of ≥100 mg/day are associated with increased risk for hepatotoxicity, many drugs are safe at such dosages. There is an unmet need to predict risk for DILI more reliably, and lipophilicity might be a contributing factor. We analyzed the combined factors of daily dose and lipophilicity for 164 US Food and Drug Administration-approved oral medications and observed high risk for hepatotoxicity (odds ratio [OR], 14.05; P < 0.001) for drugs given at dosages ≥100 mg/day and octanol-water partition coefficient (logP) ≥3. This defined the "rule-of-two." Similar results were obtained for an independent set of 179 oral medications with 85% of the rule-of-two positives being associated with hepatotoxicity (OR, 3.89; P < 0.01). Using the World Health Organization's Anatomical Therapeutic Chemical classification system, the rule-of-two performed best in predicting DILI in seven therapeutic categories. Among 15 rule-of-two positives, 14 were withdrawn from hepatotoxic drugs, and one was over-the-counter medication labeled for liver injury. We additionally examined drug pairs that have similar chemical structures and act on the same molecular target but differ in their potential for DILI. Again, the rule-of-two predicted hepatotoxicity reliably. Finally, the rule-of-two was applied to clinical case studies to identify hepatotoxic drugs in complex comedication regimes to further demonstrate its use.Apart from dose, lipophilicity contributes significantly to risk for hepatotoxicity. Applying the rule-of-two is an appropriate means of estimating risk for DILI compared with dose alone.
Postoperative Biliocutaneous Fistula: Successful Treatment by Insertion of an Endoprosthesis
Authors: W. van Steenbergen, A. Haemers, W. Pelemans, E. Ponette, J. Vanwing, E. Verbeken, J. Fevery
Journal: Endoscopy (1987)

An elderly patient with a postoperative biliocutaneous fistula, the persistence of which was due to an unrecognized fibro-malignant stricture of the distal common bile duct, was treated by the insertion of an endoscopic biliary endoprosthesis. Immediately after the procedure, bile discharge through the fistula ceased completely, and the fistula closed in three days. Endoscopic treatment methods are worth trying before surgical revision of a biliocutaneous fistula is performed.
Porphyria cutanea tarda after allogeneic bone marrow transplantation for chronic myelogenous leukemia
Authors: D. Guyotat, J. F. Nicolas, F. Augey, D. Fiere, J. Thivolet
Journal: American Journal of Hematology (1990)

Abstract A case of porphyria cutanea tarda (PCT) occurring after bone marrow transplantation (BMT) is reported. A 43‐year‐old male with chronic myelogenous leukemia received an human leukocyte antigen (HLA)‐identical allogeneic transplantation with T‐cell depleted marrow. Because of graft rejection, a second transplant was performed 4 months later. A grade II acute graft‐ vs.‐host disease and a cytomegalovirus (CMV) infection were subsequently observed. Two years after the second transplant, cutaneous symptoms of PCT with typical biochemical abnormalities developed. Liver biopsy revealed signs of hepatitis with iron overload. CMV was isolated from liver tissue. The possible roles of underlying disease, BMT, and CMV liver disease are discussed in view of the recently reported cases of PCT in patients with AIDS or hematological disorders.