tbuckley/cabot-search huggingface dataset:
Functional and ultrastructural features of ethanol/bile salts interaction in the isolated perfused rat liver
Authors: Domenico Alvaro, Antonio Benedetti, Alessandro Gigliozzi, Adriano Bini, Paola Della Guardia, Tiziana la Rosa, Anne Marie Jezequel, Livio Capocaccia
Journal: Hepatology (1995)

We investigated whether bile salts (BS) with different hydrophobic-hydrophilic properties interact with ethanol on bile secretion, enzyme (aspartate transaminase [AST], lactate dehydrogenase [LDH]) release in the perfusate, liver ultrastructure, and vesicular exocytosis in the isolated perfused rat liver. Ethanol (0.1 or 1%) promoted a rapid decrease of bile flow and BS secretion in livers perfused with taurocholate (TCA), the physiologic BS in the rat (-28% decrease of baseline values with 0.1% and -34% with 1% ethanol). The inhibitory effect of ethanol on bile flow and BS secretion was significantly (P < .02) attenuated by perfusing liver with the hydrophilic BS, tauroursodeoxycholate (TUDCA), and it was exacerbated (P < .02) by perfusion with the hydrophobic BS, taurodeoxycholate (TDCA). The release of AST and LDH in the perfusate was unaffected by 0.1% ethanol, but increased threefold to fivefold by 1% ethanol in TCA-perfused livers. This cytolitic effect of ethanol was not observed in TUDCA-perfused livers, but it was enhanced (P < .03) by perfusion with TDCA. No ultrastructural abnormalities were found in either TCA- or TUDCA-perfused livers, with or without 1% ethanol. Only minimal changes were found in livers perfused with TDCA alone, but, in the presence of TDCA, 1% ethanol induces marked mitochondrial damage. The biliary excretion of the fluid phase marker horseradish peroxidase was inhibited by ethanol, an effect reversed by TUDCA (P < .02) and exacerbated by TDCA (P < .04). In conclusion, this study demonstrates that hydrophilic BS such as TUDCA counteract the inhibitory effect of ethanol on bile secretion and vesicular exocytosis as well as the ethanol-induced cytolitic effect in the isolated perfused rat liver. In the presence of hydrophobic BS such as TDCA, the exposure to ethanol promotes a marked inhibition of bile secretion and vesicular exocytosis as well as prominent mitochondrial damage.
Phosphoinositide 3-kinase signalling in the vascular system
Authors: F. Morello, A. Perino, E. Hirsch
Journal: Cardiovascular Research (2008)

Phosphoinositide 3-kinases (PI3Ks) are protein and lipid kinases activated by different classes of membrane receptors, including G-protein coupled and tyrosine kinase receptors. Several lines of evidence have uncovered specific roles for distinct PI3K isoforms in the vascular system in both physiology and disease. The present review will summarize and discuss the most recent advances regarding PI3K-Akt signalling in endothelial cells, vascular smooth muscle cells, platelets, and inflammatory cells involved in the atherosclerotic process. Of interest, the development of novel isoform-selective PI3K inhibitor drugs offers a unique opportunity to selectively and differentially target PI3K-driven pathways in the vascular system and may give rise to new strategies for the treatment of cardiovascular diseases.
Doctor convicted of terrorism related offences in US is struck off by GMC
Authors: C. Dyer
Journal: BMJ (2012)

A London GP from Sri Lanka who spent four and a half years in a US jail for aiding the Tamil Tigers has been struck off the UK medical register.

Murugesu Vinayagamoorthy, 62, was caught in an undercover sting in which he was recorded attempting to bribe purported US state department officials to remove the Liberation Tigers of Tamil Eelam (LTTE) from a list of designated foreign terrorist organisations.

Dr Vinayagamoorthy wanted to return to the practice in Enfield, north London, that he ran with his wife. But a GMC …
AID-Dependent Activation of a MYC Transgene Induces Multiple Myeloma in a Conditional Mouse Model of Post-Germinal Center Malignancies
Authors: Marta Chesi, Davide F. Robbiani, Michael Sebag, Wee Joo Chng, Maurizio Affer, Rodger Tiedemann, Riccardo Valdez, Stephen E. Palmer, Stephanie S. Haas, A. Keith Stewart, Rafael Fonseca, Richard Kremer, Giorgio Cattoretti, P. Leif Bergsagel
Journal: Cancer Cell (2008)
Amenorrhea in Premenopausal Women After Adjuvant Chemotherapy for Breast Cancer
Authors: Janice M. Walshe, Neelima Denduluri, Sandra M. Swain
Journal: Journal of Clinical Oncology (2006)

Chemotherapy and ovarian ablation both independently improve survival in premenopausal women with hormone-sensitive breast cancer. Amenorrhea is a well-recognized occurrence after chemotherapy. The rate of chemotherapy-induced amenorrhea varies with patient age and chemotherapy regimens administered. However, the impact of chemotherapy-induced amenorrhea on prognosis is still being defined. Older studies in premenopausal women argue that the benefit with chemotherapy is a result of direct cytotoxicity alone. However, studies that restrict outcome analysis to hormone receptor-positive tumors suggest that chemotherapy has a dual mechanism in women with hormone-responsive tumors; indirect endocrine manipulation secondary to chemotherapy-induced ovarian suppression and direct cytotoxicity. The significant health ramifications involved with the induction of premature menopause as well as potential benefits necessitate a comprehensive evaluation of chemotherapy-induced amenorrhea. This review will discuss the incidence of amenorrhea with commonly-used adjuvant chemotherapeutic regimens, the possible benefits of chemotherapy-induced amenorrhea, and the challenges of interpreting the existing data in breast cancer trials.
Radiologic Technology and the Medical Student
Authors: Andrew S. Gorajski
Journal: JAMA (1970)

Within every human relationship there is a need, and a desire for satisfaction of that need—a common bond, a common goal. In this case, the goal is the diagnosis of the patient's illness, the relief of his symptoms, and the removal of the cause of his ailment. Since there is a common goal, I believe that the medical student and the radiologic student should seek mutual acceptance. Because both are still in training, the ultimate need most likely will not arise until each has attained his degree. An x-ray technologist is dependent on the physician so that he can put his skills, training, and experience to work. Unlike a secretary, who can find employment in any firm, industry, or hospital, a technologist is employed only or almost completely in the health industry. On the other hand, the physician needs time to devote to the ever-increasing number of patients. He does
BRIDGE FORMATION AND CYTOPLASMIC FLOW BETWEEN PHAGOCYTIC CELLS
Authors: Moshe Aronson
Journal: The Journal of Experimental Medicine (1963)

A simple chamber was constructed for observation of cells at 37 degrees C and under high magnification. Rabbit peritoneal histiocytes observed in this chamber manifested a constant interaction, which lasted as long as the preparation itself. This interaction consisted of formation of cytoplasmic bridges and flow of cytoplasm between the cells. Lung macrophages formed bridges both between themselves, and with peritoneal histiocytes. On the other hand, no bridges were noticed between histiocytes and polymorphonuclears or fibroblasts. BCG bacteria were observed passing from one histiocyte to another. Autoradiographic studies suggest that RNA may be transferred from one cell to another. The possible significance of these observations is discussed.
RELIGION, NATIONAL ORIGIN, IMMIGRATION, AND MENTAL ILLNESS
Authors: BERTRAM H. ROBERTS, JEROME K. MYERS
Journal: American Journal of Psychiatry (1954)

A survey of the prevalency of patients with mental illness who were under treatment in New Haven was analyzed according to religion, national origin, and immigrational status. It was found that psychoneurotic disorders were more frequent among Jews whereas the rate of affective disorder in this group had fallen to the average of the population. Alcoholism is most prevalent among the Irish Catholics. There has been a general fall in the rate of organic mental disease, particularly in that of general paresis among Negroes. The illness of senescence and the affective illnesses are higher in the foreign-born while psychoneurotic disorders are more frequent in the native-born. Schizophrenia and psychosis with mental deficiency are not related to the social variables. Comparisons were made between these findings and previous studies. Speculative explanations are offered to explain the trends and disproportions.
COSTA RICA, ITS PHYSICIANS AND MEDICAL INSTITUTIONS.
Authors: N. SENN
Journal: JAMA (1901)

The short midwinter vacation I am spending in Costa Rica has afforded me an excellent opportunity to study the diseases of this little republic and to become acquainted with its leading medical men and its most important institutions devoted to the care of the sick. Costa Rica is the smallest of the Central American republics. Its present population does not exceed 300,000, and is made up largely of Indians, Jamaica negroes and Spaniards, with a small sprinkling of whites from the United States and the different European countries. The coast on both sides is low and swampy to the base of the mountains. The low lands supply the world with bananas, and the mountain sides are covered with coffee plantations. The interior is mountainous and picturesque, a Switzerland plus the tropical forests and impenetrable jungles. Along the coast the heat is depressing, being greatly aggravated by the ever-present atmospheric humidity.
Clinician scientists face difficult future
Authors: P. Sharma
Journal: BMJ (1998)

EDITOR—Bitter criticism has been levelled at the Calman changes,1 but nothing has been said of the 100 or so people in Britain who hold clinician scientist fellowships.2 Only four funding bodies award these fellowships: the Medical Research Council, Wellcome Trust, British Heart Foundation, and Cancer Research Campaign. Together they provide around £30 million of support for these individuals. The success rate for applicants in these competitive fellowships is consistently only 25%. These awards, universally regarded as successful and cost effective, …
Pyrimidine nucleoside phosphorylase activity in tumour and matched normal gastrointestinal mucosa.
Authors: B Higley, J Oakes, J De Mello, G R Giles
Journal: Gut (1982)

5-Fluorouracil (5-FU) requires activation to the metabolites FdUMP and FUTP for its cytotoxic effect. This activation involves the intracellular enzymes uridine and thymidine phosphorylase. We have assayed the levels of these enzymes in colorectal and gastric cancers and have shown that, in the majority of cases, the enzyme levels were higher than in the adjacent normal mucosa. It is suggested that, while the ratio tumour/normal mucosa enzyme activity may give some indication of the relative toxicity of 5-FU in these tissues, the absolute activities of the phosphorylases in tumour tissue could give a better indication of tumour responsiveness.
Human Multidrug Resistance Protein 7 (<i>ABCC10</i>) Is a Resistance Factor for Nucleoside Analogues and Epothilone B
Authors: Elizabeth Hopper-Borge, Xiu Xu, Tong Shen, Zhi Shi, Zhe-Sheng Chen, Gary D. Kruh
Journal: Cancer Research (2008)

Abstract Multidrug resistance protein 7 (MRP7; ABCC10) is an ATP-binding cassette transporter which is able to transport amphipathic anions and confer resistance to docetaxel and, to a lesser extent, vincristine and paclitaxel. Whereas some detail on the resistance profile of MRP7 is known, the activities of the pump have not been completely determined. Here, it is shown by the analysis of MRP7-transfected HEK293 cells that, in addition to natural product agents, MRP7 is also able to confer resistance to nucleoside-based agents, such as the anticancer agents cytarabine (Ara-C) and gemcitabine, and the antiviral agents 2′,3′-dideoxycytidine and PMEA. Consistent with the operation of an efflux pump, expression of MRP7 reduced the accumulation of Ara-C and PMEA. In addition, MRP7 is also able to confer resistance to the microtubule-stabilizing agent epothilone B. Ectopic expression of MRP7 in mouse embryo fibroblasts deficient in P-glycoprotein and Mrp1 revealed that MRP7 has a broad resistance profile for natural product agents. In this drug-sensitive cellular background, MRP7 conferred high levels of resistance to docetaxel (46-fold), paclitaxel (116-fold), SN-38 (65-fold), daunorubicin (7.5-fold), etoposide (11-fold), and vincristine (56-fold). Buthionine sulfoximine did not attenuate MRP7-conferred resistance to docetaxel or Ara-C. These experiments indicate that the resistance capabilities of MRP7 include nucleoside-based agents and a range of natural product anticancer agents that includes nontaxane antimicrotubule agents that are not susceptible to P-glycoprotein–mediated transport and that, unlike MRP1 and MRP2, MRP7-mediated drug transport does not involve glutathione. [Cancer Res 2009;69(1):178–84]
Indwelling intravenous polyethylene catheters. Factors influencing the risk of microbial colonization and sepsis
Authors: P. C. Fuchs
Journal: JAMA (1971)

To assess complications secondary to the use of indwelling intravenous polyethylene catheters, a study was conducted in which 500 catheter tips were cultured and results correlated with data obtained in each case. A catheter colonization rate of 3.8% occurred. The major factor influencing the frequency of catheter colonization is the presence of other catheter complications, such as subcutaneous infiltrations and phlebitis. The low colonization rate is attributed in part to the nature of this hospital and its patient population, and in part to the use of a team of specially trained "IV" nurses for insertion of most and maintenance care of all intravenous catheters. Frequent observation of catheters and their immediate removal at the first sign of patient distress or catheter malfunction are essential to successfully maintaining a lowered rate of colonization, infection, and septicemia.
Kaposi's sarcoma of the bowel--presenting as apparent ulcerative colitis.
Authors: J N Weber, D J Carmichael, A Boylston, A Munro, W P Whitear, A J Pinching
Journal: Gut (1985)

Persistent diarrhoea with mucus-production developed in a 37 year homosexual man, and an initial diagnosis of ulcerative colitis was made after barium enema examination and rectal biopsy. The patient later developed cutaneous lesions which proved to be Kaposi9s sarcoma, and the bowel lesion was also subsequently shown to be Kaposi9s sarcoma. This tumour occurred as a manifestation of the acquired immune deficiency syndrome (AIDS). The patient was treated with alpha interferon, with partial regression of the skin lesions, but progression of the bowel tumour. Because of severe bowel symptoms, including episodes of subacute intestinal obstruction, the localised bowel disease was treated with radiotherapy. In view of the increasing incidence of AIDS, a diagnosis of Kaposi9s sarcoma must be considered in homosexual men presenting with persistent diarrhoea, for which no infectious cause can be demonstrated.
The challenge of early systemic sclerosis for the EULAR Scleroderma Trial and Research group (EUSTAR) community. It is time to cut the Gordian knot and develop a prevention or rescue strategy
Authors: M Matucci-Cerinic, Y Allanore, L Czirják, A Tyndall, U Müller-Ladner, C Denton, G Valentini, O Distler, K Fligelstone, A Tyrrel-Kennedy, D Farge, O Kowal-Bielecka, F van den Hoogen, M Cutolo, P D Sampaio-Barros, P Nash, K Takehara, D E Furst
Journal: Annals of the Rheumatic Diseases (2009)

Early diagnosis of systemic sclerosis (SSc) may allow the start of treatment that could slow disease progression. For this reason early diagnosis of the disease is of pivotal importance. However, the lack of diagnostic criteria and valid predictors significantly limit patient evaluation and the use of potentially effective drugs in the earliest phase of SSc. Early SSc may be suspected on the basis of Raynaud's phenomenon, puffy fingers, autoantibodies and SSc capillaroscopic pattern. In practice, the aim is to have criteria for the diagnosis of very early SSc. The criteria that are proposed are obviously provisional and need to be validated: ( a ) initially through a Delphi technique; ( b ) thereafter perhaps using already available datasets; but ( c ) of critical importance, through prospective studies. Only after prospective studies can these potential criteria be considered validated. The consensus on criteria for the classification of very early SSc might be part of the evolving EULAR/ACR project of reclassification of SSc.
Reliability of Physical Signs in Patients with Severe Attacks of Ulcerative Colitis
Authors: N. G. Graham, F. T. de Dombal, J. C. Goligher
Journal: BMJ (1971)

A series of observer variation studies in a small group of patients suffering from severe acute ulcerative colitis is reported. Seventy-two separate assessments of the patients' physical signs and clinical progress were made by three independent observers.The results of this investigation suggest that there is difficulty in eliciting general physical signs such as anaemia or dehydration in these patients. By contrast, local abdominal signs such as tenderness and distension were relatively reliably elicited. The results also suggest that there are considerable problems in evaluating these clinical signs in terms of the patient's immediate subsequent progress.
Legal Aspects of the Decision Not to Prolong Life
Authors: George P. Fletcher
Journal: JAMA (1968)

New medical techniques for prolonging life force both the legal and medical professions to reexamine their traditional attitudes toward life and death. The new set of problems emerges from the following recurrent situation: a comatose patient has a flat electroencephalogram reading; according to the best judgment, he has an infinitesimal chance of recovery; he can be sustained by intravenous therapy. What should his physician do? And in making his decision, how much weight should the physician give to the wishes of the family, to the financial condition of the family, and to the prospect that his time might be profitably used in caring for patients with a better chance for recovery?  It would be a mistake to think that our legal tradition contains clear answers to these questions. If this type of case demands moral sensitivity of the physician, it demands much more of the legal theorist and of the
Primary lymph node presentation of angiocentric lymphoma associated with features of a hemophagocytic syndrome
Authors: Brian D. Kueck, Curtis A. Hanson, David E. Weissman, Katherine Bayliss
Journal: American Journal of Hematology (1989)

Abstract The spectrum of post‐thymic T‐cell neoplasia includes the angiocentric immunoproliterative lesions, a group of disorders histologically exhibiting vascular infiltration and destruction; included among these disorders is angiocentric lymphoma. In contrast to the typical extranodal presentation seen in the angiocentric immunoproiiferative lesions, this report describes a case of angiocentric lymphoma presenting as primary lymph node disease with clinicopathologic findings mimicking a hemophagocytic syndrome. Rearrangement of the T‐cell receptor beta chain documents this case to be a clonal T‐cell neoplasm. The association of this distinct histologic type of T‐cell malignancy with hemophagocytic syndromes is reviewed.
Scintigraphic Documentation of Hemorrhage from Coronary Artery Bypass Graft
Authors: JOSEPH A. ORZEL, CLINTON E. BAISDEN
Journal: Clinical Nuclear Medicine (1986)

Tc-99m labeled RBC imaging was used to conclusively demonstrate continuing intrathoracic hemorrhage from the anastomotic site of a coronary artery bypass graft. Demonstration of continuing hemorrhage and localization of the most likely site of bleeding resulted in timely and appropriate surgical intervention, which resulted in hemostasis and eventual patient recovery. Tc-99m RBC imaging may be an ideal noninvasive technique to investigate the site and activity of intrathoracic hemorrhage after coronary bypass surgery and other thoracic procedures.
Should inverse ratio ventilation be used in adult respiratory distress syndrome?
Authors: C Shanholtz, R Brower
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

IRV-induced increases in MAP are clearly associated with shunt reduction, but we find no studies that show shunt reduction without increased end-expiratory alveolar pressure. On the other hand, various studies in humans with ARDS and hyaline membrane disease and animal models of acute lung injury indicate that shunt reduction does not occur with IRV if there is no increase in end-expiratory alveolar pressure (21), that shunt reduction is the same with IRV as with conventional ventilation with PEEP when there are comparable levels of end-expiratory volume or alveolar pressure (16, 32), and that shunt reduction is greater when MAP is raised with PEEP than with IRV (27). Improved ventilation-perfusion matching with IRV is theoretically unlikely and, given the high FIO2 used in ARDS, improvements in oxygenation from more even ventilation would not be great. Deadspace reduction by extended inspiratory phase ventilation may allow only minor improvements in gas exchange (14-16, 21, 25, 26, 34). Thus, there is little evidence to indicate that oxygenation can be maintained or improved with IRV while volotrauma risk is reduced. Some have suggested that IRV may promote gradual shunt reduction over hours or days, and that slower inspiratory airflow may reduce injurious parenchymal shear forces. However, these potentially salutary effects of IRV are unproven. On the other hand, there are potential deleterious effects of IRV, including increased risk of volotrauma and the requirements for heavy sedation and neuromuscular blockage. IRV remains of unproven value in the management of ARDS.
The Clinical Management of Systemic Lupus Erythematosus
Authors: Robert S. Katz
Journal: JAMA (1984)

This is the most terrific clinical textbook on the diagnosis and management of lupus. Contributed to by Dr Peter Schur and 15 other authors, this rather short, very helpful book is jam packed with useful information and therapeutic guidelines. It is readable, up-to-date, and will be useful to any physician or student interested in lupus.  Although it lacks the size and, therefore, the quantity of information and references of the other major lupus textbooks (DuBois' Lupus Erythematosus 1976, University of Southern California Press), Schur's book chops, slices, and purees the information on lupus, blending it into a more digestible read. In it, key problems, such as the management of lupus nephritis, CNS lupus, and lupus during pregnancy are covered.  The book is strongly clinical, although there are chapters on immunopathogenesis and genetics. It is interesting that 69% of monozygotic twin pairs are concordant for lupus, whereas the concordance rate of
Hydrochloric Acid Measurements
Authors: Franz J. Ingelfinger
Journal: JAMA (1964)

<h3>To the Editor:—</h3> In the study by Leonard et al (<i>JAMA</i><b>187</b>:589 [Feb 22] 1964) how do the authors measure, and what do they mean by, "free hydrochloric acid" and "mean mEq HCl" (Fig 3)? Is the latter a concentration figure or an output per unit time? I suggest that a "Multiple Discipline Research Forum" should exercise the discipline of providing information sufficient to clarify these terms.