tbuckley/cabot-search huggingface dataset:
Management of Asymptomatic Gallstones in the Diabetic Patient
Authors: Lawrence S. Friedman
Journal: Annals of Internal Medicine (1988)

The management of asymptomatic cholelithiasis in patients with diabetes is controversial. We used decision analysis to compare expectant management to prophylactic cholecystectomy in asymptomatic diabetic patients. Relevant probabilities were derived from the literature or expert opinion. Hypothetical cohorts of patients were followed for their lifetimes under each strategy. Expectant management was almost always the superior course. For example, a 30-year-old diabetic man gains an average of 6.1 months of life by choosing expectant management over prophylactic surgery. The superiority of expectant management was invariant to changes in age, sex, and the extent to which major surgical complications affect the future quality of life. Prophylactic cholecystectomy was superior only with extremely high estimates of the likelihood of developing symptomatic disease, the probability of requiring emergency surgery after symptoms develop, and emergency surgical mortality rates. However, no single factor had sufficient impact to alter the optimal decision by itself; the probabilities of several untoward events had to be increased simultaneously to favor prophylactic cholecystectomy. Prophylactic surgery for silent gallstones in diabetic patients does not increase life expectancy or quality of life and may in fact reduce it. This result holds over a wide range of basic assumptions.
Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated cirrhotics: Meta-analysis of 5 trials
Authors: John M. Vierling, Stefan Zeuzem, Fred Poordad, Jean-Pierre Bronowicki, Michael P. Manns, Bruce R. Bacon, Rafael Esteban, Steven L. Flamm, Paul Y. Kwo, Lisa D. Pedicone, Weiping Deng, Frank J. Dutko, Mark J. DiNubile, Kenneth J. Koury, Frans A. Helmond, Janice Wahl, Savino Bruno
Journal: Journal of Hepatology (2014)
Breast is still best even when HIV prevalence is high, experts say
Authors: R. Dobson
Journal: BMJ (2002)

Child health specialists have urged governments and agencies not to provide free formula milk in programmes aimed at preventing mother to child HIV transmission. They say that although formula may seem to be a good idea, the consequences can be damaging.

“Free formula milk may appear to be a blessing, but while potentially decreasing the rate of postnatal …
The Mystery of Prothrombin-Time Methods
Authors: Armand J. Quick
Journal: JAMA (1965)

<h3>To the Editor:—</h3> From Dr. Sise's reply to my letter concerning the interpretation of prothrombin-time methods (<i>JAMA</i><b>191</b>:604 [Feb 15] 1965), it is clear that the crux of the misunderstanding is in the use of the term<i>true prothrombin</i>. If Dr. Sise will measure the prothrombin in newborn blood with his modification of the one-stage test which he claims measures true prothrombin, he will find, as was originally established with the unmodified prothrombin time, that the prothrombin is approximately the same as in adult blood. With the Iowa twostage method, the prothrombin concentration is found to be only about 25% of the adult level, or in other words, the latter contains four times more prothrombin. One could hardly conclude that the two-stage method measures false prothrombin. I have offered the explanation that the two-stage method estimates total prothrombin, whereas the onestage determines only free prothrombin. In adult blood 75%
Abstract 2771: HSP90 inhibitor NVP-AUY922 exhibits the potent antiproliferative effect in gastrointestinal cancer cells with a lack of PTEN expression
Authors: Munenori Takaoka, Xiaohong Bao, Huifang Hao, Takuya Fukazawa, Tomoki Yamatsuji, Yasuko Tomono, Kazufumi Sakurama, Yoshio Naomoto
Journal: Cancer Research (2012)

Abstract Background: The heat shock protein 90 (HSP90), a molecular chaperone, has provoked great interest as a promising molecular target for cancer treatment, since it is involved in regulating the conformation, stability and functions of key oncogenic proteins. At present, a variety of chemical compounds targeting HSP90 have been developed and have shown convincing anti-neoplastic activity in various preclinical tumor models. Several inhibitors of HSP90 have been reported exhibiting more antitumor efficacy in PTEN-null tumor xenograft. The aim of our study was to evaluate the antitumor effects of a novel HSP90 inhibitor, NVP-AUY922, in human malignant cells, especially in PTEN-null cancer cells. Materials and Methods: Human esophageal cancer (TE-1, TE-4, TE-8, TE-10), gastric cancer (NUGC-3, NUGC-3/IL), pancreatic cancer (PANC-1, MIAPACA-2, Bxpc3) and mutant c-kit-driven lymphocytes (Ba/F3-KE11, Ba/F3-K642, Ba/F3-820Mz), mimicking gastrointestinal stromal tumor cells, were examined. WST assay and/or trypan blue exclusion assay were conducted to assess the anti-proliferation effects of NVP-AUY922 in those cells mentioned above. The activity of cell growth-related molecules such as AKT, ERK, and PTEN were investigated by western blot analysis. Genetic modification using siRNA and expression vector were applied for silencing and overexpression of PTEN, respectively, in cancer cells. Results: Cell viability assays showed that NVP-AUY922 potently inhibits the proliferation of human cancer cell lines, regardless of 5-FU resistance or c-Kit mutation, by which the sensitivity to imatinib can be affected. PTEN-null TE-4 cells exhibited more sensitivity to NVP-AUY922. Interestingly, The sensitivity to NVP-AUY922 was increased by silencing PTEN expression in intact PTEN-expressing TE-10 cells and decreased by exogenous transduction of PTEN in TE-4 cells. Furthermore, NVP-AUY922 significantly inhibited the activity of AKT and ERK in TE-4 cells, but not in TE-10 cells. Conclusion: Inhibition of Hsp90 function by NVP-AUY922 exhibited strong cytotoxicity against most of the cancer cells, including some anticancer drug-resistant cells, revealing its potential for a novel therapeutic alternative to cancer treatment. In addition, this study suggests that the expression status of PTEN determines the sensitivity to HSP90 inhibitor for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2771. doi:1538-7445.AM2012-2771
Parents, Family Doctors, and Acute Appendicitis in Childhood
Authors: R. H. Jackson
Journal: BMJ (1963)

The problem of acute appendicitis in childhood is not yet solved. Nevertheless, because it is a common condition many of us feel we understand the disease and are satisfied with the way in which it is managed. There are some grounds for this complacent attitude in the steady fall in the number of deaths in England and Wales from appendicitis: in 1947 there were 305 deaths from this disease, and in 1957 only 69. This improvement has occurred at all ages in children in whom the appendix has ruptured, while the unruptured appendix carries a low and unchanged mortality rate of under 0.5% (Skyrme Rees, 1952 ; Fraser and McCredie, 1955 ; Mason Brown, 1956 ; Foster and Edwards, 1957 ; Minervini and Santulli, 1958). The collectiye experience of these authors suggests that this improvement is due to better surgical and paediatric care rather than to earlier diagnosis. However, we cannot accept with complacency the deaths of 69 children with a curable disease, and when we turn from mortality to morbidity the situation is most unsatisfactory. Too many children still have a general or local peritonitis at operation, and many of these recover only after much suffering, anxiety, and hard work. Mason Brown (1956) said:  While some success has been achieved in retrieving the disaster of delay in diagnosis, we cannot entirely over come the handicap which late diagnosis entails, and many of the very ill children who survived did so by a narrow margin. Improvements in surgical and paediatric techniques have not been matched by prompter diagnosis, and there is little evidence that children are being operated on earlier. Mason Brown (1956), in Edinburgh, found that during the last three years of his survey (1952-4) the percentage of children with general peritonitis was higher than in the period 1929 51. Even more striking figures come from the Boston Children's Hospital, where Hudson and Chamberlain (1939), Scott and Ware (1945), and Longino, Holder, and Gross (1958) found that in 1928-39 43.1% of 848 children had a ruptured appendix, whereas in 1939-44 there were 45.2% of 234, and in 1944-57 45% of 1,328 had ruptured. The percentage of children presenting with a perforated appendix is therefore higher now than it was 30 years ago. This suggests that further improvements in the results of treatment of acute appendicitis are more likely to come from improvements in diagnosis than from improvements in technique or management. In this paper a series of 313 children with acute appendi citis is analysed in an attempt to discover whether similar delay in diagnosis occurs in our community and the reasons for it. I was personally responsible for the general care of these children, and although a few years have elapsed since they were in hospital it is unlikely that there have been improvements in diagnosis sufficient to invalidate the conclusions. Clinical Material
Arrhythmia: Diagnosis and Management: A Clinical Electrocardiographic Guide
Authors: Robert J. Henning
Journal: JAMA (1986)

The purpose of this textbook is to illustrate the common cardiac arrhythmias and the patterns of acute myocardial infarction. The current diagnostic criteria for cardiac arrhythmias and myocardial infarction are presented. Nonspecific terminology and misunderstandings are avoided because the authors strictly adhere to the definitions and classification of cardiac arrhythmias recommended by the World Health Organization and the International Society and Federation of Cardiology. The textbook is extensively illustrated with excellent reproductions of colored electrocardiographic tracings, which are printed on the same scale as the original electrocardiograms. As most of the figure legends explain the characteristics of the electrocardiographic tracings in some detail, the book may be used as an atlas of cardiac arrhythmias and myocardial infarctions. In addition, each chapter represents an entity in itself. Basic cardiac anatomy and physiology as well as the fundamentals of electrocardiography are briefly reviewed. Ten chapters are devoted to the illustration and discussion
A Medical Mystery: Dilated Bowel — The Answer
Authors: Jason Handwerker, Vassilios D. Raptopoulos
Journal: New England Journal of Medicine (2007)

Reznick and MacRae (Dec.21 issue) 1 report on the current status of simulation in surgical-skills training and its various applications.Another potential use of simulation is as a part of the curriculum for medical students, with an aim to introduce hands-on skills training and evaluation early in their career.During surgical clerkships, only 67% of surveyed students thought that the surgical teaching and exposure they had received was adequate, 2 and the majority of the exposure involved minor, "less risky" parts of surgical procedures, such as tying knots or cutting sutures.Perhaps the exposure of students to surgical simulation would allow them to appreciate their own technical ability, would reveal whether they were interested in participating in technical procedures, and would therefore influence their choice of residency training.
Residential and recreational acquisition of possible estuary-associated syndrome: a new approach to successful diagnosis and treatment.
Authors: R C Shoemaker
Journal: Environmental Health Perspectives (2001)

Evidence suggests that the estuarine dinoflagellates, Pfiesteria piscicida Steidinger & Burkholder and P. shumwayae Glasgow & Burkholder, members of the toxic Pfiesteria complex (TPC), may release one or more toxins that kill fish and adversely affect human health. In the current study we investigated the potential for undiagnosed cases of possible estuary-associated syndrome (PEAS), as termed by the Centers for Disease Control and Prevention (CDC), in a population that had residential and/or recreational exposure to TPC-affected estuaries, but that did not have direct contact with fish kills or lesioned fish. Age-adjusted visual contrast sensitivity (VCS) was significantly lower and the presence of PEAS-associated symptoms was much higher in the estuary cohort (n = 77) than in combined-control cohorts (n = 87), one without exposure to bodies of water (n = 53) and one with exposure to marine waters (n = 34). In the estuary cohort, 37 individuals met the CDC case definition for PEAS and had significantly lower VCS than non-PEAS cases. The VCS improved and symptoms abated after 2 weeks of treatment with cholestyramine. Cholestyramine, the original drug approved for treatment of hypercholesterolemia, has previously been reported to enhance the elimination rates of a variety of toxins, presumably by interruption of enterohepatic recirculation through toxin entrapment in its polymeric structure and/or anion-exchange process. Control studies showed that repeated VCS testing alone did not improve VCS scores and that cholestyramine treatment did not affect VCS in patients with elevated cholesterol levels. These results suggested that a) susceptible individuals may acquire PEAS through residential and/or recreational contact with TPC-affected estuaries in the absence of an active fish kill; b) VCS is a useful indicator in PEAS diagnosis and treatment monitoring; and c) PEAS can be effectively treated with cholestyramine. Because the study did not use population sampling techniques, the results do not indicate PEAS prevalence. Furthermore, definitive diagnosis of PEAS and association with TPC toxin(s) must await identification of, and a serologic test for, the putative TPC toxin(s).
Diagnosis of Radiosensitive Hypothalamic Tumors Without Craniotomy
Authors: A. M. Spiegel, G. Di Chiro, P. Gorden, A. K. Ommaya, J. Kolins, T. C. Pomeroy
Journal: Annals of Internal Medicine (1976)

Three patients with intracranial atypical teratomas presented with symptoms of endocrine dysfunction (diabetes insipidus, hyperprolactinemia, and anterior hypopituitarism) suggestive of a hypothalamic disorder. Computer-assisted tomography done in two of the three cases enabled us to document the presence of a mass and institute radiotherapy, without prior neurosurgical exploration. Computer-assisted tomography also provided a safe and effective method of assessing the effects of radiotherapy.
Role of fibronectin in Pneumocystis carinii attachment to cultured lung cells.
Authors: S T Pottratz, W J Martin
Journal: Journal of Clinical Investigation (1990)

Attachment of pathogens to host cells is a prerequisite for the development of many infections. Pneumocystis carinii (PC) pneumonia is characterized by attachment of PC trophozoites to the alveolar epithelium. The mechanism of this process is unknown. Fibronectin (Fn) is a glycoprotein present in the alveolar space known to mediate cell-cell attachment, including the attachment of certain pathogens to host epithelial cells. In this study the binding of Fn to PC trophozoites has been characterized in vitro using 125I-Fn. Fn binds saturably and specifically to 6.4 x 10(5) binding sites per organism with an apparent binding constant, Kd, of 1.2 x 10(-8) M. Fn binding to PC was inhibited by the addition of Arg-Gly-Asp-Ser (RGDS), a tetrapeptide containing the active site of the cell-binding domain of Fn. PC attachment to an alveolar epithelial cell line was quantified using 51Cr-labeled PC trophozoites. Attachment was decreased from 24 +/- 1.9% to 12.1 +/- 1% (P less than 0.01) by the addition of an anti-Fn antibody, an effect that could be overcome by the addition of excess free Fn. It is concluded that binding of Fn to PC may be an important initial step in the attachment of the organism to alveolar epithelial cells. Furthermore, it appears that PC recognizes and binds to the RGDS cell attachment site of Fn.
Generic drug firm settles claim that it was paid to stay out of market
Authors: O. Dyer
Journal: BMJ (2015)

A big manufacturer of generic drugs has had to pay $512m (£340m; €470m) to settle a claim that it took payments in various guises from the drug company Cephalon in exchange for not producing a cheap generic version of the company’s best selling drug. 

Teva was one of four generic drug makers named in an antitrust suit brought by a large group of bulk drug buyers, pharmacies, and US health insurance plans over an alleged scheme to avert generic competition for the sleep disorder drug modafinil (marketed in the United States as Provigil).1 The other manufacturers, Ranbaxy, Mylan, and Barr Pharmaceuticals, remain defendants in the suit. The same alleged scheme is the subject of a separate suit by the Federal Trade Commission against Cephalon, due to be heard in June.

Provigil’s main patent expired in 2003, but the drug’s maker, Cephalon, still held minor patents related to particle size of the active ingredient. Generic …
Abstract C42: MLKs regulate the activities of the small GTPases, Rho and Rac, to drive both single cell and collective cell migration in breast cancer invasion
Authors: Chotirat Rattanasinchai, Sean Misek, Jian Chen, Kathleen A. Gallo
Journal: Cancer Research (2013)

Abstract Most mortality of breast cancer patients is caused by metastasis to vital organs. One of the key steps of breast cancer metastasis is invasion through the basement membrane, which is controlled by several signaling cascades including small GTPases, Rho and Rac. Mixed lineage kinases (MLKs) are a family of MAP3Ks that activate multiple MAPK pathways, including the c-Jun N-terminal kinase (JNK) pathway. Our lab has determined that MLK3-JNK signaling is critical for migration, invasion and metastasis of triple negative breast cancer cells. Herein, the effect of a small molecule pan-MLK inhibitor on tumor cell migration in 2D wound healing and in 3D dissemination in collagen type I, the most abundant collagen in the body, was determined. Cancer cells can utilize distinct modes of migration. MDA-MB-231 and 4T1 cells were chosen as models for the study of single and collective cell migration, respectively. In addition, the effect of MLK3 on Rho-GTP and Rac-GTP levels was determined. Data from this study demonstrate that an MLK inhibitor is sufficient to block migration of multiple breast cancer cell lines in wound healing assays. Furthermore, this inhibitor dramatically reduces the dissemination of cancer cell lines that utilize single, as well as, collective cell migration. Silencing of MLK3 results in enhanced Rho activity and decreased Rac activity, as well as defective focal adhesion turnover. Inhibition of the activity of MLKs or the downstream MAPK, JNK, also increases Rho activity, which is accompanied by an increase in the number and/or size of focal adhesions and an increase in actin stress fibers. Consistent with the idea that MLK inhibition reduces migration through relieving Rho suppression, addition of a Rho/ROCK inhibitor, Y-27632, partially rescues the migratory defect of MLK inhibition by reducing peripheral focal adhesions and actin stress fibers. Taken together, these data suggest that MLK3 could play a role in controlling the balance between Rac and Rho activity required for cancer cell migration and invasion. Thus, MLK inhibitors could be therapeutically useful in the context of breast cancer metastasis. Citation Format: Chotirat Rattanasinchai, Sean Misek, Jian Chen, Kathleen A. Gallo. MLKs regulate the activities of the small GTPases, Rho and Rac, to drive both single cell and collective cell migration in breast cancer invasion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C42.
Evaluation of liver mitochondrial function through breath test with 13C-methionine labeled in different positions
Authors: M. Candelli, A. Armuzzi, M.A. Zocco, E.C. Nista, A. Grieco, L. Miele, S. Di Caro, P. Pola, G. Gasbarrini, A. Gasbarrini
Journal: Journal of Hepatology (2001)
The Pathology of OEdema
Authors: W. S. Lazarus-Barlow
Journal: BMJ (1895)

MKIALU TcRNAL 691 advanced cases, and is usually regarded as being a sign of more value than cutaneous pigmentation.It may be found along the line of contact of the lips, on the cheeks, gums, or tongue, especially if there be any cause of irritation, such as a carious tooth.It is said to occur in the vagina'9.The conjunctivee60 may in some cases, though very rarely, be pigmented.Situation of the Pigment on the Mucous Membrane.-Accordiing
Blood tests urged for CJD carriers
Authors: J. Siegel-Itzkovich
Journal: BMJ (1997)

Four Israeli scientists have urged that all Jewish residents of Libyan or Tunisian origin should undergo a blood test to identify carriers of Creutzfeldt-Jakob disease (CJD) before they may donate blood or organs.

Although the fatal genetic disease affects one in a million of the general Israeli population, it is 100 times more common among these …
Notes upon Lanolin
Authors: W. G. Smith
Journal: BMJ (1886)

TuB BRTLI2t MEDICA.L\J ?N4L.LW6up well, leaving only the state of chronic bronchitis, from which she had latterly suffered.Of course, her strength was much lowered by the attack, anxi she never thoroughly regained it.Some three weeks be- fore death, her brain began, to show evidence of her exhaustion, by its failing power, drowsiness, etc., although her mind, up to thjs time, had remained remarkably clear.Five days before her death she had a convulsive seizure; and, although this passed off, ohe grzdually be- came less and less clear, taldrg less nourishxaent, and finally, as, it were, slept away.Her marvellous power of vita3ity was shown by her so thoroughly throwing off such a severe pneumonia, which would have killed many a far younger woman."Miss Hastings was a typical instance of an aged person: of.long- lived family, of strong constitution, all the organs bei-ng strong and well balanced; with good appetite and digestion, but a moderate or small eater, taking little alcohol, and not much meat ; with regular action of bowels; of spare frame, robust, energetic, and of benevolent, happy disposition; of good abilitv, with usually good health; taking a fair amount of out-of-door exercise; having no illness till near the close of her life; and, at a very advanced age, showing retarkable power of recovering from severe attacks-bronchitis, erysipelas, pneumonia,-thus resisting the savage onslaughts of disease, and yielding at last to the .slow, steady, orderly advancing developmentaI processes by which the natural termination of life is brought about.