tbuckley/cabot-search huggingface dataset:
The Effect of Glucose on Urinary Cation Excretion during Chronic Extracellular Volume Expansion in Normal Man
Authors: Edward J. Lennon, J. Lemann, W. F. Piering, L. S. Larson
Journal: Journal of Clinical Investigation (1974)

Both glucose administration and extracellular volume expansion augment urinary calcium and magnesium excretion. While volume expansion also augments sodium excretion, glucose induces an antinatriuresis. To examine the interrelationships of volume expansion and of glucose administration on sodium, calcium, and magnesium excretion, the effects of glucose were evaluated during clearance studies in the same subjects before and after chronic extracellular volume expansion produced by desoxycorticosterone acetate (DOCA) and a normal dietary sodium intake. The augmentation of U(Ca)V and U(Mg)V by glucose was simply additive to the increments in divalent cation excretion caused by "escape" from the sodium-retaining effects of DOCA. Glucose administration reduced U(Na)V, an effect exaggerated after DOCA escape and associated with reductions in volume/glomerular filtration rate (V/GFR) and C(Na) + C(H2O)/GFR, suggesting augmented proximal tubular reabsorption. Before glucose, U(Na) was inversely correlated with U(G), and after glucose administration C(Na)/GFR was inversely correlated with T(G)/GFR. We propose that the availability of glucose in the proximal tubule stimulates Na reabsorption while delaying development of a chloride diffusion potential, thereby inhibiting tubular reabsorption of Ca and Mg.
Impact of HLA disparity in the graft-versus-host direction on engraftment in adult patients receiving reduced-intensity cord blood transplantation
Authors: Naofumi Matsuno, Atsushi Wake, Naoyuki Uchida, Kazuya Ishiwata, Hideki Araoka, Shinsuke Takagi, Masanori Tsuji, Hisashi Yamamoto, Daisuke Kato, Yoshiko Matsuhashi, Sachiko Seo, Kazuhiro Masuoka, Shigesaburo Miyakoshi, Shigeyoshi Makino, Akiko Yoneyama, Yoshinobu Kanda, Shuichi Taniguchi
Journal: Blood (2009)
Origin of Both Great Vessels from the Right Ventricle Associated with the Trisomy-18 Syndrome
Authors: TERRY R. ROGERS, JACK W. C. HAGSTROM, MARY ALLEN ENGLE
Journal: Circulation (1965)

Origin of both great vessels from the right ventricle in association with a ventricular septal defect was found in seven of nine autopsied patients with the clinical features of the trisomy-18 syndrome. In four of these patients trisomy-18 was confirmed by chromosomal analyses. This experience indicates that origin of both great vessels from the right ventricle may in fact be an additional component of the trisomy-18 syndrome. Human Genetics, for chromosomal analyses and for consultation.
A Late Phase of Cerebellar Long-Term Depression Requires Activation of CaMKIV and CREB
Authors: Sohyun Ahn, David D. Ginty, David J. Linden
Journal: Neuron (1999)

Recently, it has been shown that cerebellar LTD has a late phase that may be blocked by protein synthesis inhibitors. To understand the mechanisms underlying the late phase, we interfered with the activation of transcription factors that might couple synaptic activation to protein synthesis. Particle-mediated transfection of cultured Purkinje neurons with an expression vector encoding a dominant inhibitory form of CREB resulted in a nearly complete blockade of the late phase. Kinases that activate CREB were inhibited, and LTD was assessed. Inhibition of PKA or the MAPK/RSK cascades were without effect on the late phase, while constructs designed to interfere with CaMKIV function attenuated the late phase. These results indicate that the activation of CaMKIV and CREB are necessary to establish a late phase of cerebellar LTD.
Time for a putsch of the l'oreal consultants?
Authors: J. Ross
Journal: BMJ (2013)

Spence makes many important points.1 I don’t want to indulge in consultant bashing, but some of us seem to have forgotten the reason that we are in the position we are in—to care for patients.

The consultant contract needs reorganisation so we can have consultant delivered care across all specialties, with trainees aiding the services, not maintaining them.

Yes it …
Control of proximal tubule fluid reabsorption in experimental glomerulonephritis.
Authors: D A Maddox, C M Bennett, W M Deen, R J Glassock, D Knutson, B M Brenner
Journal: Journal of Clinical Investigation (1975)

We have recently shown that in the early autologous phase of nephrotoxic serum nephritis (NSN) single nephron glomerular filtration rate is unchanged from values in normal hydropenic control rats, but that single nephron filtration fraction and efferent arteriolar oncotic pressure (piE) are reduced because of a marked reduction in the glomerular capillary ultrafiltration coefficient. The present study was undertaken to examine the influence of this decline in piE as well as the other known determinants of peritubular capillary fluid exchange on absolute proximal fluid reabsorption (APR) in NSN. The findings indicate that APR and proximal fractional reabsorption are reduced significantly in NSN, relative to values in a separate group of age and weight-matched normal hydropenic control rats studied concurrently. In addition to the measured decline in piE, efferent arteriolar plasma flow (Qe) and peritubular capillary hydraulic pressure (Pc) were found to increase significantly, while interstitial oncotic pressure, estimated from hilar lymph, was not significantly different from values in control rats. Using a mathematical model of peritubular capillary fluid uptake we found that, assuming that the capillary permeability-surface area product and interstitial hydraulic pressure are unchanged in NSN, the observed changes in piE and Pc are sufficient to offset the effect of the increase in QE, yielding a calculated reduction in APR of approximately 4 nl/min, in excellent agreement with the observed mean decline of 4.1 nl/min. These findings suggest that control of APR in NSN is mediated by the same factors that regulate APR under normal physiological conditions, namely, the imbalance of forces governing peritubular capillary uptake of isotonic reabsorbate.
Retroperitoneal perforation caused by endoscopic biopsy in a patient with ulcerative colitis and cytomegalovirus infection
Authors: H. Miyatani, Y. Yoshida
Journal: Endoscopy (2007)

A 52-year-old woman was admitted to our hospital for initiation of treatment for ulcerative colitis. She was given 2-week course of ganciclovir because she was positive for cytomegalovirus (CMV) antigens. Colonoscopy was performed 2 months after she started prednisolone treatment, which showed multiple ulcers with a well-defined, punched-out appearance, erosions, and diffuse redness in the colon. The colonoscopic findings were consistent with ulcerative colitis exacerbated by CMV infection. Multiple biopsy specimens were taken using a standard biopsy forceps (2.2-mm cup, non-spiked). A pinhole-like perforation occurred at the time of the biopsy of the rectal ulcer base (Figure [1]). Computed tomography revealed a pneumoretroperitoneum (Figure [2]). A diagnosis of retroperitoneal perforation was made and she was treated with an antibiotic and remained on a nil-by-mouth regime for 1 week. Because the patient still tested positive for CMV antigens, a 2-week course of treatment with gancyclovir was started on day 71. The patient made a rapid and uneventful recovery and was discharged on day 84.
Gastric microcirculatory changes of Portal-hypertensive rats can be attenuated by long-term Estrogen-progestagen treatment
Authors: Julián Panés, Maria Casadevall, Mercedes Fernández, Josep M. Piqué, Jaume Bosch, Roser Casamitjana, Isabel Cirera, Josep A. Bombí, Josep Terés, Juan Rodés
Journal: Hepatology (1994)

It has been suggested that estrogen–progestagen therapy may be useful in preventing bleeding from gastric angiodysplasia, a vascular lesion similar to that described in portal–hypertensive gastropathy. In this study we assessed the effects of estrogen–progestagen therapy on gastric microcirculation and systemic and splanchnic hemodynamics in portal–hypertensive and sham–operated rats. One week after the surgical procedure (partial portal vein ligation or sham surgery), animals were given an intramuscular injection of a slow–release preparation of estrogen–progestagen or its vehicle. Two weeks later, gastric mucosal blood flow was measured by means of hydrogen gas clearance, a morphometrical analysis of gastric mucosal blood vessels was performed and systemic and splanchnic hemodynamics were evaluated with a radiolabeled–microspheres technique. In portal–hypertensive rats, estrogen–progestagen therapy induced a significant reduction in gastric mucosal blood flow, number of blood vessels and relative area of vessels. Similar changes, although of lesser magnitude, were achieved with estrogen or progestagen given separately and with the low dose of combined estrogen–progestagen. Estrogen–progestagen treatment also induced significant reductions in portal pressure and portocollateral resistance without changing systemic or splanchnic hemodynamics. In contrast, estrogen–progestagen treatment did not induce changes in any of the parameters studied in sham–operated rats. We conclude that long–term estrogen–progestagen therapy reduces the gastric hyperemia, increased mucosal vessel density and portal pressure in portal–hypertensive rats. (Hepatology 1994;20:1261-1270).
Remarks ON THE INFLUENCE OF WIND ON PHTHISIS
Authors: W. Gordon
Journal: BMJ (1903)

THIERE is a wonderful want of agreement amongst medical authorities as to the influence of wind on phthisis, and the most widely divergent views have been expressed on the sub- ject, some maintaining that wind is injurious, others that it is non-injurious or even beneficial, others again that it may be injurious or beneficial according to circumstances.This divergence of opinion is especially unfortunate at the present time, when the curability of many cases of phthisis by open- air treatment is fully recognized, and when sites are being chosen in many parts of the country for the erection of sana- toria.A few quotations will illustrate how widely opinions differ.Wind Injurious.Dr. Haviland, who has made such a careful study of the distribution of phthisis mortality in the registration districts of England and Wales, goes so far as to say that " with the facts before him ......... no medical man would send a consump- tive case to live where he would be subject to the full force of prevailing winds."'Sir Hermann Weber says " My own expe- rience has been that strong wind from any quarter.........is in- jurious to consumptive people, and seems to increase the mortality.2Wind Harmless.Dr. Theodore Williams says, "Some authorities object strongly to wind in a health station for consumptives, but I am in favour of its ventilating and purifying influence in the case of all diseases of germ origin, and protection by shelters can be successfully secured when wind is excessive."3Dr.
Molecular basis underlying Huntington's chorea found
Authors: D. Josefson
Journal: BMJ (1997)

The molecular mechanism underlying several inherited neurodegenerative disorders has been uncovered, a discovery that should lead to new approaches to treatment.

Huntington's chorea and spinocerebellar ataxia type III, two autosomally dominant diseases that lead to late onset dementia and crippling movements, are caused by an abnormal expansion of the DNA trinucleotide sequence cytosine-adenine-guanine ( Cell 1997;90:537-8 and Neuron 1997;19:333-44). This sequence codes …
Only five out of 19 maternity units in Ireland are following recent advice, report finds
Authors: M. Houston
Journal: BMJ (2013)

A report from Ireland’s patient safety watchdog has found that the Health Service Executive failed to act on a series of recommendations made by previous investigations into maternity care, some of which may have helped prevent the death of 31 year old dentist Savita Halappanavar at University Hospital Galway last October.

The Health Information and Quality Authority’s investigation into her death from sepsis when 17 weeks pregnant …
Abstract 13422: Molecular Imaging of Vascular and Myocardial 18F-FDG Uptake with PET/CT in Patients Early After an Acute Coronary Syndrome
Authors: Carolin Sonne, Susanne Weissmueller, Stephan G Nekolla, Sandra van Marwick, Albert Schomig, Markus Schwaiger
Journal: Circulation (2010)

Objectives: The study tested the hypothesis that the metabolic signal caused by activated macrophages allows the localization of the culprit lesion early after an acute coronary syndrome (ACS) by 1...
The memoir of an opium eater
Authors: T. Dalrymple
Journal: BMJ (2009)

A friend of mine who lived for a time in America started every conversation at a party by saying, “Hello, I’m A . . . I hate my parents, don’t you?”

He never knew his opening gambit to draw anything but assent, he said, suggesting that filial piety, like fortitude, is no longer considered a virtue these days.

How different from Reverend George Crabbe’s charming and reverent memoir of his father, the Reverend George Crabbe, published in 1834, two years after Crabbe senior’s death.

Crabbe senior was apprenticed to a surgeon but preferred poetry as a vocation to medicine. Nevertheless he continued all the days of his …
Overview of Gene Expression Profiling and Novel Translational Technologies in Breast Cancer.
Authors: C. Perou
Journal: Cancer Research (2009)

Abstract Gene expression profiling has had an enormous impact on many aspects of breast cancer, including elucidation of the basic mechanisms of carcinogenesis and mammary development, prediction of outcome and response to treatment, and identification of new subtypes of disease. Importantly, gene expression profiling in breast cancer has allowed the development of biomarkers that are being used in the clinic and/or will become part of routine clinical care in the near future. Genomic profiling is accomplished nowadays by using genome-wide DNA microarray assays, which evaluate thousands of genes with relatively low sensitivity, or qRT-PCR assays, which evaluate small numbers of genes with high sensitivity. The majority of these assays focus on mRNA molecules; however, in recent years, DNA microarrays evaluating other functionally important classes of RNA molecules, such as microRNAs and non-coding RNAs, have been developed and will likely have an impact on our understanding of breast cancer biology. Nonetheless, DNA microarrays and qRT-PCR assays based on mRNA have provided robust platforms for the investigation of breast cancer transcriptomes, and each has resulted in the development of clinically useful prognostic tests (i.e. OncotypeDX and Mammaprint). However, as with all technologies, new methods and platforms are constantly being developed, offering higher speed, lower cost and increased accuracy. Importantly, many of these promising new technologies are compatible with RNA derived from archival formalin-fixed paraffin embedded materials. Therefore, it is likely that gene expression-based assays will continue to play a critical role in the development of novel biomarkers, and the discovery of new targets. In this session, we will cover the basics of DNA microarrays and microarray statistics, and discuss the next generation of technologies to further study the gene expression patterns of breast cancers. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr ES3-1.
Chimeric Antigen Receptors With Mutated IgG4 Fc Spacer Avoid Fc Receptor Binding and Improve T Cell Persistence and Antitumor Efficacy
Authors: Mahesh Jonnalagadda, Armen Mardiros, Ryan Urak, Xiuli Wang, Lauren J Hoffman, Alyssa Bernanke, Wen-Chung Chang, William Bretzlaff, Renate Starr, Saul Priceman, Julie R Ostberg, Stephen J Forman, Christine E Brown
Journal: Molecular Therapy (2014)

The success of adoptive therapy using chimeric antigen receptor (CAR)–expressing T cells partly depends on optimal CAR design. CARs frequently incorporate a spacer/linker region based on the constant region of either IgG1 or IgG4 to connect extracellular ligand-binding with intracellular signaling domains. Here, we evaluated the potential for the IgG4-Fc linker to result in off-target interactions with Fc gamma receptors (FcγRs). As proof-of-principle, we focused on a CD19-specific scFv-IgG4-CD28-zeta CAR and found that, in contrast to CAR-negative cells, CAR+ T cells bound soluble FcγRs in vitro and did not engraft in NSG mice. We hypothesized that mutations to avoid FcγR binding would improve CAR+ T cell engraftment and antitumor efficacy. Thus, we generated CD19-specific CARs with IgG4-Fc spacers that had either been mutated at two sites (L235E; N297Q) within the CH2 region (CD19R(EQ)) or incorporated a CH2 deletion (CD19Rch2Δ). These mutations reduced binding to soluble FcγRs without altering the ability of the CAR to mediate antigen-specific lysis. Importantly, CD19R(EQ) and CD19Rch2Δ T cells exhibited improved persistence and more potent CD19-specific antilymphoma efficacy in NSG mice. Together, these studies suggest that optimal CAR function may require the elimination of cellular FcγR interactions to improve T cell persistence and antitumor responses. The success of adoptive therapy using chimeric antigen receptor (CAR)–expressing T cells partly depends on optimal CAR design. CARs frequently incorporate a spacer/linker region based on the constant region of either IgG1 or IgG4 to connect extracellular ligand-binding with intracellular signaling domains. Here, we evaluated the potential for the IgG4-Fc linker to result in off-target interactions with Fc gamma receptors (FcγRs). As proof-of-principle, we focused on a CD19-specific scFv-IgG4-CD28-zeta CAR and found that, in contrast to CAR-negative cells, CAR+ T cells bound soluble FcγRs in vitro and did not engraft in NSG mice. We hypothesized that mutations to avoid FcγR binding would improve CAR+ T cell engraftment and antitumor efficacy. Thus, we generated CD19-specific CARs with IgG4-Fc spacers that had either been mutated at two sites (L235E; N297Q) within the CH2 region (CD19R(EQ)) or incorporated a CH2 deletion (CD19Rch2Δ). These mutations reduced binding to soluble FcγRs without altering the ability of the CAR to mediate antigen-specific lysis. Importantly, CD19R(EQ) and CD19Rch2Δ T cells exhibited improved persistence and more potent CD19-specific antilymphoma efficacy in NSG mice. Together, these studies suggest that optimal CAR function may require the elimination of cellular FcγR interactions to improve T cell persistence and antitumor responses.
Multifactorial Primary Prevention of Cardiovascular Diseases in Middle-aged Men
Authors: Tatu A. Miettinen
Journal: JAMA (1985)

In a randomized five-year multifactorial primary prevention trial of vascular diseases, hyperlipidemias, hypertension, smoking, obesity, and abnormal glucose tolerance of the high-risk test group (n=612 men) were treated with dietetic-hygienic measures and hypolipidemic (mainly probucol and clofibrate) and antihypertensive (mainly diuretics and β-blockers) agents. A matched high-risk control group (n=610) and a low-risk control group (n=593) were not treated. The program markedly improved the risk factor status, yet the five-year coronary incidence tended to be higher in the intervention group than in the control group (3.1% vs 1.5%), while the stroke incidence was significantly reduced (1.3% vs 0%). The coronary events tended to be accumulated in subgroups treated with β-blocking agents or clofibrate, but there were few in those receiving probucol or diuretics. Thus, the intervention program significantly reduced development of stroke, but the occurrence of cardiac events was not prevented. Possible adverse drug effects offsetting the probable benefit of improved risk profile are not excluded. (<i>JAMA</i>1985;254:2097-2102)
Gonadotrophin-releasing hormone analogues: a novel treatment for premenstrual asthma
Authors: R.D. Murray, J.P. New, P.v Barber, S.m Shalet
Journal: European Respiratory Journal (1999)

Premenstrual exacerbation of asthma, as reflected by a reduction in peak expiratory flow rate (PEFR), has been demonstrated in 40-100% of female asthmatics. Epidemiological data demonstrate that admission to hospital with an exacerbation of asthma occurs more frequently perimenstrually. Therapeutic interventions aimed at modifying this precipitating factor, however, remain limited. We report on a 32-yr old female with asthma in whom a marked increase in symptoms and reduction in PEFR occurred premenstrually, necessitating recurrent admissions to hospital. Frequent severe exacerbations resulted in the chronic use of oral maintenance corticosteroids. In order to suppress gonadotrophin secretion and ovarian function, a long-acting gonadotrophin-releasing hormone analogue was administered with a view to inducing a reversible menopause. This resulted in improvement in respiratory symptoms, the absence of PEFR dips premenstrually, a reduction in maintenance prednisolone dosage and no further hospital admissions during a follow-up period of 14 months. The authors propose that gonadotrophin-releasing hormone-analogue therapy is a rational and innovative adjuvant treatment worthy of further study in cases of severe premenstrual asthma.
An Unusual Case of Orthopnea
Authors: Probal K Moulik, Justine Hadcroft
Journal: New England Journal of Medicine (2002)

Figure 1. A 62-year-old former smoker presented with a 20-year history of breathlessness that worsened when she lay flat and particularly when she swam. Chest radiography (Panel A) showed an elevated left hemidiaphragm and a mediastinal shift to the right. Fluoroscopy revealed a paradoxical movement of the left hemidiaphragm. Spirometry demonstrated a forced vital capacity of 1.28 liters when the patient was supine that increased to 1.44 liters when she stood. Magnetic resonance imaging of the chest (Panel B) revealed a defect in the left hemidiaphragm (black arrows), with herniation of the stomach and colon (white arrow) into the chest. . . .