tbuckley/cabot-search huggingface dataset:
Clinical application of deferasirox: Practical patient management
Authors: Elliott Vichinsky
Journal: American Journal of Hematology (2007)

Abstract Deferasirox (Exjade®, ICL670) is a once‐daily, oral iron chelation agent that is now widely available for the treatment of transfusional hemosiderosis in adult and pediatric patients aged ≥2 years of age. Clinical evaluation has established the efficacy and safety of this novel agent in patients with a variety of chronic anemias. Deferasirox represents a significant advance in the treatment of iron overload, as the availability of an effective oral therapy has the potential to relieve many patients from the burden of frequent parenteral therapy with the previous reference standard iron chelator, deferoxamine. The most common drug‐related adverse events seen in the core registration trials were gastrointestinal disturbances, rash, mild and nonprogressive increases in serum creatinine levels, and elevations in liver enzyme levels. Most events were transient, mild‐to‐moderate in severity, and easily managed without discontinuation of treatment. As with any new agent, it is important that treating physicians are familiar with the adverse event profile of deferasirox and how the associated effects can be readily managed to ensure optimal use of this important treatment. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Induction of p38, tumour necrosis factor-α and RANTES by mechanical stretching of keratinocytes expressing mutant keratin 10R156H
Authors: M. Obarzanek-Fojt, B. Favre, M. Huber, S. Ryser, A.M. Moodycliffe, P.-J. Wipff, B. Hinz, D. Hohl
Journal: British Journal of Dermatology (2010)

Epidermolytic hyperkeratosis (bullous congenital ichthyosiform erythroderma), characterized by ichthyotic, rippled hyperkeratosis, erythroderma and skin blistering, is a rare autosomal dominant disease caused by mutations in keratin 1 or keratin 10 (K10) genes. A severe phenotype is caused by a missense mutation in a highly conserved arginine residue at position 156 (R156) in K10.To analyse molecular pathomechanisms of hyperproliferation and hyperkeratosis, we investigated the defects in mechanosensation and mechanotransduction in keratinocytes carrying the K10(R156H) mutation.Differentiated primary human keratinocytes infected with lentiviral vectors carrying wild-type K10 (K10(wt)) or mutated K10(R156H) were subjected to 20% isoaxial stretch. Cellular fragility and mechanosensation were studied by analysis of mitogen-activated protein kinase activation and cytokine release.Cultured keratinocytes expressing K10(R156H) showed keratin aggregate formation at the cell periphery, whereas the filament network in K10(wt) cells was normal. Under stretching conditions K10(R156H) keratinocytes exhibited about a twofold higher level of filament collapse compared with steady state. In stretched K10(R156H) cells, higher p38 activation, higher release of tumour necrosis factor-α and RANTES but reduced interleukin-1β secretion compared with K10(wt) cells was observed.These results demonstrate that the R156H mutation in K10 destabilizes the keratin intermediate filament network and affects stress signalling and inflammatory responses to mechanical stretch in differentiated cultured keratinocytes.
Three Europeans win Nobel medicine prize for discovering HIV and HPV
Authors: G. Watts
Journal: BMJ (2008)

The 2008 Nobel prize for physiology or medicine has gone to one German and two French researchers for microbiological detective work that led to the discovery of two families of viruses with a major impact on human health. Almost as noteworthy, say some commentators, is the absence of one US researcher whose contribution was controversial.

Francoise Barre-Sinoussi, 61, of the virology department at the Institut Pasteur in Paris, shares half the prize of 10 million Swedish kronor (£800 000; €1m; $1.4m) with Luc Montagnier, 76, director of the World Foundation for …
Asymmetrical transmission of human herpesvirus 8 among spouses of patients with Kaposi sarcoma
Authors: A. Dupuy, T. Schulz, S. Chevret, F. Agbalika, C. Pellet, M. Janier, N. Dupin, O. Vérola, F. Calvo, C. Lebbé
Journal: British Journal of Dermatology (2008)

Among heterosexuals, the sexual transmission of human herpesvirus 8 (HHV8) has not been established.To assess HHV8 seroprevalence in spouses of patients with classic and endemic Kaposi sarcoma (KS) and to suggest possible routes of transmission.A case-control study was carried out in a teaching hospital among spouses of human immunodeficiency virus-negative patients with KS (cases - exposed subjects) and controls who did not have KS nor were related to patients with KS (nonexposed subjects). HHV8 seroprevalence in spouses of patients with KS was compared with HHV8 seroprevalence in controls matched for age, gender and place of birth. Other serology tests were compared between cases and controls. Among heterosexual couples, HHV8-seropositive and HHV8-seronegative spouses were compared for possible risk factors for virus transmission.HHV8 seroprevalence was significantly higher among spouses of patients with KS (13 of 22; 59%) than among matched controls (19 of 58; 33%; P = 0.043). Among heterosexual couples, five of five (100%) male spouses were HHV8 positive vs. six of 15 (40%) female spouses (P = 0.04). There was no significant difference between HHV8-seropositive and HHV8-seronegative spouses for all other factors screened for among heterosexual couples.Being a spouse of a patient with KS is a risk factor for HHV8 seropositivity. Our results suggest that female-to-male HHV8 transmission could be more efficient than male-to-female transmission among couples including a patient with KS. Transmission could involve distinctive behaviours, or currently unknown biological properties of HHV8.
Effects of ionophore A23187 on base-line and vasopressin-stimulated sodium transport in the toad bladder.
Authors: W Wiesmann, S Sinha, S Klahr
Journal: Journal of Clinical Investigation (1977)

The cation specific ionophore A23187 (Io) is a useful tool for studying the role of intracellular Ca++ (Ca++)i in physiologic processes. The present studies explore the role of (Ca++)i on Na transport in the toad bladder. Scraped bladder cells exposed to 1 muM Io for 60 min took up 100% more 45Ca than control cells. Io, 1 muM, added to the serosal side of bladders incubated in standard Ringers containing 2.5 mM Ca++ inhibited short circuit current (SCC) values by a mean of 30% at 60 min and 50% at 90 min. Io did not inhibit SCC significantly in bladders incubated in Ringers containing 0.2 mM Ca++. These data indicate that the effects of Io on SCC depend on the levels of external Ca++ and suggest that entry of Ca++ into cells mediates the inhibition of base-line SCC. PReincubation of the bladders with either lanthanum chloride or pentobarbital prevented the increased 45Ca uptake produced by ionophore as well as theinhibition of SCC caused by the antibiotic. Vasopressin, antidiuretic hormone (ADH). 10 MU/ml, increased peak SCC by 247% in bladders preincubated for 1 h in Ringers with 2.5 mM Ca++ and 1 muM Io and by 318% in control bladders (P less than 0.01). Bladders exposed to 1 muM Io in Ringers with 0.2 mM Ca++ had an increase in SCC after ADH comparable to that observed in controls. Since the effects of ADH on SCC are mediated by cyclic AMP, we tested the effects of Io on cAMP production by scraped toad bladder cells. ADH increased cAMP from 8 to 30 pmol/mg protein in controls but it did not increase cAMP over base-line values in the presence of Io when the Ringers contained 2.5 mM Ca++. Io did not inhibit cAMP production in response to ADH when the Ca++ in the Ringers was 0.2 mM. The results indicate that Io inhibits baseline and ADH stimulated SCC by increasing (Ca++)i or Ca++ bound to the cell membrane. It is suggested that: ()( (Ca++)i or membrane-bound Ca++ plays a key role in base-line and ADH stimulated Na transport in the toad bladder; (2) inhibition of ADH stimulated SCC may be due inpart to decreased cAMP generation in response to ADH when (Ca++)i or membrane-bound Ca++ levels are increased.
Endothelial Dysfunction, Oxidative Stress, and Risk of Cardiovascular Events in Patients With Coronary Artery Disease
Authors: Thomas Heitzer, Titus Schlinzig, Karoline Krohn, Thomas Meinertz, Thomas Münzel
Journal: Circulation (2001)

Background Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations. Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events. This study was designed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease. Methods and Results Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography. The effect of the coadministration of vitamin C (24 mg/min) was assessed in a subgroup of 179 patients. Cardiovascular events, including death from cardiovascular causes, myocardial infarction, ischemic stroke, coronary angioplasty, and coronary or peripheral bypass operation, were studied during a mean follow-up period of 4.5 years. Patients experiencing cardiovascular events (n=91) had lower vasodilator responses to acetylcholine ( P &lt;0.001) and sodium nitroprusside ( P &lt;0.05), but greater benefit from vitamin C ( P &lt;0.01). The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation ( P =0.001), the effect of vitamin C ( P =0.001), and age ( P =0.016) remained independent predictors of cardiovascular events. Conclusions Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease. These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity.
UK does well on giving information to patients but poorly on access to new treatments
Authors: Rory Watson
Journal: BMJ (2007)

The United Kingdom ranks only 17th out of 29 countries in the latest edition of the Euro Health Consumer Index of public healthcare systems—one place behind Ireland and narrowly ahead of Italy and Portugal. It has slipped from 15th position last year.⇓





The rankings, now in their third year, were produced by the Brussels based analysis and information organisation, Health Consumer Powerhouse. They are based on 27 indicators grouped into five categories—patients' rights and information, waiting times, outcomes, the generosity of public healthcare systems, and access to medication.

The UK, with its electronic patient records, quality ranking of hospitals provided by the Healthcare Commission, and 24 hour telephone healthcare information system provided by NHS Direct is in the forefront of patient access to information. However, it scores badly …
RIGHT PARADUODENAL HERNIA
Authors: GUNTHER W. NAGEL
Journal: JAMA (1923)

Examples are recorded in the literature of passage of the intestines through the foramen of Winslow, through the mesenteries, under the cecum, into the intersigmoid fossa and other peritoneal pockets, notably those about the duodenojejunal flexure. The last named constitute the so-called paraduodenal hernias, of which there are two types: left and right. Approximately 100 cases of left paraduodenal hernias have been recorded, and in a thorough search of the literature I have found twenty-eight of the right. The following case is an example of the latter:  REPORT OF A CASE  The hernia, unsuspected in life, was found at necropsy in a man, aged 55, on whom a diagnosis of general carcinomatosis had been made during an exploratory laparotomy. He had complained for many years of a slight feeling of discomfort in the right lower abdominal region after meals. Two months before his death, he began having dull, aching pains
Complications of Gastric Freezing
Authors: Robert H. Holland, Dimitry Morkovin
Journal: JAMA (1963)

GASTRIC FREEZING is not an innocuous procedure. Like any operation it is subject to errors in judgment and technique, and may be attended with side effects and complications. This is particularly true when the method is utilized in poorrisk patients by overzealous or inexperienced personnel. The dearth of reactions and sequelae resulting from gastric freezing, reported by Wangensteen and his associates,<sup>1-6</sup>is a tribute to their careful laboratory and clinical application of the method. It is advisable, therefore, that physicians who employ this form of therapy be properly trained by competent preceptors, and that they and the medical profession in general realize that the procedure is still in its formative state. The following case study describes the effect of freezing on organs and tissues adjacent to the bed of a gastric ulcer. <h3>Report of a Case</h3> A 32-year-old white female was transferred to this hospital on July 4, 1962,
Efficiency of energy transfer from pressure-volume area to external mechanical work increases with contractile state and decreases with afterload in the left ventricle of the anesthetized closed-chest dog.
Authors: T Nozawa, Y Yasumura, S Futaki, N Tanaka, M Uenishi, H Suga
Journal: Circulation (1988)

We studied the effects of ventricular end-systolic elastance (Ees) and effective arterial elastance (Ea) on the efficiency of energy transfer from pressure-volume area (PVA) to external mechanical work (EW) in the left ventricle of anesthetized closed-chest dogs. PVA represents the total mechanical energy generated by ventricular contraction, which is an intermediate form of energy between oxygen consumption, the total energy input, and EW, the effective energy output. PVA and EW were determined from ventricular pressure and volume, which were continuously measured with a volumetric conductance catheter. Measurements of Ees were obtained by transiently increasing afterload by an inflation of a Fogarty catheter in the thoracic descending aorta. Ea was determined as the ratio of end-systolic pressure to stroke volume. The EW/PVA efficiency of a steady-state contraction increased from 55% to 64%, with a 58% increase in Ees after dobutamine. Ees, which was smaller than Ea before dobutamine, became nearly equal to Ea after dobutamine, maximizing EW for a given end-diastolic volume. EW/PVA efficiency decreased with an abrupt increase in afterload before and after dobutamine. The sensitivity of the decrease in the EW/PVA efficiency to an increase in end-systolic pressure was significantly less after than before dobutamine. We could account for all these changes in EW/PVA efficiency by the relative changes in Ees and Ea in the pressure-volume diagram.
Complementary DNA cloning of the alternatively expressed endothelial cell glycoprotein Ib beta (GPIb beta) and localization of the GPIb beta gene to chromosome 22.
Authors: M D Kelly, D W Essex, S S Shapiro, F J Meloni, T Druck, K Huebner, B A Konkle
Journal: Journal of Clinical Investigation (1994)

Glycoprotein Ib# (GPIb#) exists in platelets disulfide-linked to glycoprotein Iba (GPIba), a major receptor for von Willebrand factor.Both GPIba and GPIb# are expressed in endothe- lial cells (EC).While the GPIba mRNA and protein appear similar in platelets and EC, EC GPIbft mRNA is larger than platelet GPIb#t and encodes a larger protein.We have cloned and sequenced EC GPIbfi cDNA and report a 2793-nucleotide sequence which contains a 41 1-amino acid open reading frame.The EC sequence contains all of the platelet cDNA sequence and all but three amino acids of the primary translation prod- uct.Like the genes encoding GPIba, GPIX, and GPV, the GPIb# gene appears simple in structure.Using human hamster hybrids, we have localized the GPIbfl gene to chromosome 22pter --22q11.2.When we examined poly (A)' RNA from several human tissues for GPIb,8 mRNA expression, we found that GPIbfl mRNA was expressed in a variety of tissues but was most abundant in heart and brain, while GPIba and GPIX mRNA expression was found only in lung and placenta at very low levels.The broad distribution of GPIb# mRNA suggests that it may be playing a role different than or additional to its function in platelets.(
Allogeneic marrow transplantation for myeloproliferative disorders other than chronic myelogenous leukemia: Review of forty cases
Authors: Donna Przepiorka, Sergio Giralt, Issa Khouri, Richard Champlin, Carlos Bueso-Ramos
Journal: American Journal of Hematology (1998)

The role of allogeneic marrow transplantation as treatment of myeloproliferative disorders other than chronic myelogenous leukemia is not yet determined. At our center, 1 patient with primary myelofibrosis, 1 with mastocytosis, and 4 with myeloid metaplasia have been transplanted using HLA-identical sibling donors. All patients engrafted with full donor chimerism, and morphologic and cytogenetic manifestations of disease in the marrow resolved posttransplant. Three patients died; two with relapse and one from infection. The other three patients are alive in remission at 24+, 28+, and 32+ months posttransplant. Including these cases, a total of 40 patients transplanted for myeloproliferative disorders have been reported. The most common indications for transplantation were cytopenias, increasing blasts in marrow or blood, uncontrolled counts on conventional therapy, poor prognosis cytogenetics, organ dysfunction, and consolidation after induction therapy for blast transformation. Using the outcome data published for these patients, the actuarial estimate of 3-year survival is 55% (95% C.I., 44–76%) with a median reported follow-up of survivors of 21 months (range, 4–158 months). For patients with myeloproliferative disorders and evidence of accelerated disease, HLA-identical marrow transplantation is well tolerated and can result in an extended disease-free survival. Am. J. Hematol. 57:24–28, 1998. © 1998 Wiley-Liss, Inc.
A CASE OF ONE CEREBRAL HEMISPHERE SUPPLYING BOTH SIDES OF THE BODY
Authors: G. H. Grills
Journal: BMJ (1906)

A FEW days ago a lady consulted me about a throbbing in her neck, which she said was very conspicuous when she was in evening dress and was a frequent subject of remark among her friends.When the neck was exposed, very marked pulsation was seen just above the sternum, also a pulsating swelling, extending for 2 in.upwards, above the inner end of the right clavicle, looking at first like an aneurysm of the innominate artery.On examining this swelling, the right carotid and subelavian arteries were found to come off from its upper end, and the Phrenic 'AC/
What mentally ill offenders need.
Authors: D. Chiswick
Journal: BMJ (1992)

label."Expiry date" will be at the top of the label.Below the hospitals on the implications for hospital practices of the blood group (ABO and Rh) and the regional blood transfusion changes in labelling.centre will be recorded both sets of information in written andCountries that have changed from coloured to black and bar code form.The "Date bled" will be immediately below white labels have done so successfully.Even if an interthis information.national colour coding agreement was achieved in the future, Also from 1 April the Rh type on most red cell packs will reverting to coloured labels may not be popular as black and refer to the Rh D group only.Thus, red cells will be labelled white labels can be readily printed in house.The discipline of Rh D positive or Rh D negative, which will meet most reading the blood group on the label instead of looking at the requirements.Additional Rh typing to provide further colour may not be so readily accepted as an advantage.It must information concerning the Rh group will be performed at be conceded, however, that this principle is one that accords regional transfusion centres, and these specially typed units of with good clinical practice.It is no different from the well red cells will be available when required.recognised practice of reading the name of a drug on the During the next few weeks this important change in container before giving it.labelling will receive wide publicity.Posters will be available H H GUNSON in hospitals together with a leaflet illustrating the change to National Director, black and white labels.Both of these measures will supple-National Blood Transfusion Service, ment discussions between staff in transfusion centres and Manchester M60 7LP
"Benadryl" in Treatment of Oxyuriasis
Authors: O. H. Siung
Journal: BMJ (1950)

<h3>Abstract</h3> Defining mode of action is vital for both developing new drugs and predicting potential resistance mechanisms. African trypanosome pentamidine and melarsoprol sensitivity is predominantly mediated by aquaglyceroporin 2 (TbAQP2), a channel associated with water/glycerol transport. TbAQP2 is expressed at the flagellar pocket membrane and chimerisation with TbAQP3 renders parasites resistant to both drugs. Two models for how TbAQP2 mediates pentamidine sensitivity have emerged; that TbAQP2 mediates pentamidine translocation or via binding to TbAQP2, with subsequent endocytosis, but trafficking and regulation of TbAQPs is uncharacterised. We demonstrate that TbAQP2 is organised as a high order complex, is ubiquitylated and transported to the lysosome. Unexpectedly, mutation of potential ubiquitin conjugation sites, i.e. cytoplasmic lysine residues, reduced folding and tetramerization efficiency and triggered ER retention. Moreover, TbAQP2/TbAQP3 chimerisation also leads to impaired oligomerisation, mislocalisation, and increased turnover. These data suggest that TbAQP2 stability is highly sensitive to mutation and contributes towards emergence of drug resistance.
TCTAP A-062 Incidence, Predictors and Outcomes of Transient Slow Coronary Flow Appearing Just After Paclitaxel-Coated Balloon Angioplasty
Authors: Hideyuki Kawashima, Nobuaki Suzuki, Yusuke Watanabe, Hiroyuki Kyono, Ken Kozuma, Takaaki Isshiki
Journal: Journal of the American College of Cardiology (2015)
Enhancement of Hematopoietic Stem Cell Repopulating Capacity and Self-Renewal in the Absence of the Transcription Factor C/EBPα
Authors: Pu Zhang, Junko Iwasaki-Arai, Hiromi Iwasaki, Maris L. Fenyus, Tajhal Dayaram, Bronwyn M. Owens, Hirokazu Shigematsu, Elena Levantini, Claudia S. Huettner, Julie A. Lekstrom-Himes, Koichi Akashi, Daniel G. Tenen
Journal: Immunity (2004)