tbuckley/cabot-search huggingface dataset:
Absorption of calcium and magnesium in patients with intestinal resections treated with medium chain fatty acids
Authors: K V Haderslev
Journal: Gut (2000)

Steatorrhoea is associated with increased faecal loss of calcium and magnesium. Medium chain C8-C10 triglycerides (MCTs) improve fat absorption in patients with small bowel resections but the effects on intestinal absorption of divalent cations are not clear.To assess the effect of dietary replacement of long chain triglycerides (LCTs) with MCTs on calcium and magnesium absorption in patients with small bowel resections.Nineteen adult patients with a remaining small intestine averaging 171 cm (range 50-300).In a crossover design, patients were randomised to two high fat diets (10 MJ/day, 50% as fat) for four days each separated by one day of washout. Diets were prepared in duplicate and were based on either LCT (LCT period) or equal quantities of LCT and MCT (L/MCT period). Metabolic balances were calculated during the last three days of each period.Mean stool volume increased significantly with the L/MCT diet and was 336 ml more than that with the LCT diet (95% confidence interval of mean difference, 26-649 ml). There was no significant change in the net absorption of calcium and magnesium between the two diets. On average, percentage calcium absorption was 8.6% with the LCT diet and 12.5% with the L/MCT diet. Mean percentage magnesium absorption was 5.4% with the LCT diet and 2.9% with the L/MCT diet.Dietary replacement of 50% long chain triglycerides with medium chain triglycerides in small bowel resected patients increased faecal volume significantly. No changes in the intestinal net absorption of calcium and magnesium were demonstrated.
Antibody-Mediated Delivery of Interleukin-2 to the Stroma of Breast Cancer Strongly Enhances the Potency of Chemotherapy
Authors: Jessica Mårlind, Manuela Kaspar, Eveline Trachsel, Roberto Sommavilla, Stuart Hindle, Camilla Bacci, Leonardo Giovannoni, Dario Neri
Journal: Clinical Cancer Research (2008)

Abstract Purpose: There is an interest in the discovery of biopharmaceuticals, which are well tolerated and which potentiate the action of anthracyclines and taxanes in breast cancer therapy. Experimental Design: We have produced a recombinant fusion protein, composed of the human antibody fragment scFv(F16) fused to human interleukin-2 (F16-IL2), and tested its therapeutic performance in the MDA-MB-231 xenograft model of human breast cancer. The F16 antibody is specific to the alternatively spliced A1 domain of tenascin-C, which is virtually undetectable in normal tissues but is strongly expressed in the neovasculature and stroma of breast cancer. Results: When used as monotherapy, F16-IL2 displayed a strikingly superior therapeutic benefit compared with unconjugated recombinant IL-2. The administration of doxorubicin either before (8 days, 24 h, or 2 h) or simultaneously with the injection of F16-IL2 did not decrease the accumulation of immunocytokine in the tumor as measured by quantitative biodistribution analysis. Therapy experiments, featuring five once per week coadministrations of 20 μg F16-IL2 and doxorubicin, showed a statistically significant reduction of tumor growth rate and prolongation of survival at a 4 mg/kg doxorubicin dose but not at a 1 mg/kg dose. By contrast, combination of F16-IL2 with paclitaxel (5 and 1 mg/kg) exhibited a significant therapeutic benefit compared with paclitaxel alone at both dose levels. F16-IL2, alone or in combination with doxorubicin, was well tolerated in cynomolgus monkeys at doses equivalent to the ones now used in clinical studies. Conclusions: F16-IL2 may represent a new useful biopharmaceutical for the treatment of breast cancer.
Inactivation of Smad4 Accelerates KrasG12D-Mediated Pancreatic Neoplasia
Authors: Kyoko Kojima, Selwyn M. Vickers, N. Volkan Adsay, Nirag C. Jhala, Hyung-Gyoon Kim, Trenton R. Schoeb, William E. Grizzle, Christopher A. Klug
Journal: Cancer Research (2007)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human malignancies, with an overall 5-year survival rate of &amp;lt;5%. Genetic analysis of PDAC patient samples has shown that specific disease-associated mutations are correlated with histologically defined stages of neoplastic progression in the ductal epithelium. Activating mutations in KRAS are almost uniformly present in early-stage disease, with subsequent inactivating mutations in p16INK4A, p53, and SMAD4 occurring in more advanced lesions. In this study, we have tested whether the loss of Smad4 would cooperate with an activating KrasG12D mutation to promote progression to PDAC using the Pdx1-Cre transgenic system to activate KrasG12D and delete Smad4 in all pancreatic lineages including the ductal epithelium. Analysis of double-mutant mice showed that loss of Smad4 significantly accelerated the progression of pancreatic intraepithelial neoplasias (mPanIN) and promoted a high incidence of intraductal papillary mucinous neoplasia and active fibrosis compared with Pdx1-Cre;KrasG12D or Pdx1-Cre;Smad4lox/lox mice. Occasionally, double-mutant mice progressed to locally invasive PDAC with little evidence of metastases by 6 months of age and without the detectable loss of p53 or p16Ink4A expression or function. The loss of Smad4 only seemed to promote disease progression in the presence of the activated KrasG12D allele because we observed no abnormal pathology within the pancreata of 23 Pdx1-Cre;Smad4lox/lox animals that were analyzed up to 8 months of age. This indicates that Smad4 is dispensable for normal pancreatic development but is critical for at least partial suppression of multiple KrasG12D-dependent disease-associated phenotypes. [Cancer Res 2007;67(17):8121–30]
Wnt'er in liver: Expression of Wnt and frizzled genes in mouse
Authors: Gang Zeng, Farrukh Awan, Wade Otruba, Peggy Muller, Udayan Apte, Xinping Tan, Chandrashekhar Gandhi, Anthony J. Demetris, Satdarshan P. S. Monga
Journal: Hepatology (2006)

The Wnt signaling pathway is essential for a wide array of developmental and physiological processes. Wnts are extracellular ligands that bind to frizzled (Fz) receptors at the membrane, canonically inducing β-catenin nuclear translocation and activation. Although β-catenin has been shown to be critical in liver biology, the expression of the 19 Wnt and 10 Fz genes in liver remains undetermined. We report comprehensive analysis of Wnt and Fz expression in whole liver as well as individual cell types: freshly isolated and plated hepatocytes, biliary epithelial cells, normal and activated stellate and Kupffer cells, and sinusoidal endothelial cells (SECs). Oligonucleotides for the 19 Wnt, 10 frizzled receptors genes, and secreted Frizzled-related protein-1 (sFRP or Fzb) were synthesized based on the available sequences. A total of 11 Wnts and 8 Fz genes and Fzb were expressed in normal liver. Although only 6 Wnt and 5 Fz genes were expressed in freshly isolated hepatocytes, 8 Wnt genes, 7 Fz genes, and Fzb were expressed in plated hepatocytes. Although 12 Wnt and 7 Fz genes were expressed in biliary tree, additional Fz9 and Fzb were only expressed in cultured biliary epithelial cells. The same 14 Wnt and 7 Fz genes were expressed in both activated and normal stellate and Kupffer cells; only Fzb was expressed in their activated state. Also, 11 Wnt, seven Fz, and Fzb genes were expressed in SECs. Conclusion : These data indicate that most Wnt and frizzled genes are expressed in the liver and might be playing important roles in liver pathobiology via canonical and noncanonical pathways. Hepatology 2007;45:195–204.)
Relief of heterogeneous symptoms after successful gall bladder stone lithotripsy and complete stone disappearance.
Authors: U Stolzel, C Koszka, B Wolfer, U Kleine, W Pommerien, E O Riecken
Journal: Gut (1994)

The symptoms of 100 patients with gall bladder stone disease were prospectively analysed before and after successful treatment with extracorporeal shock wave lithotripsy (ESWL) and oral bile acids. This is of considerable clinical interest because complaints after cholecystectomy persist in 21-47% of patients (postcholecystectomy syndrome). Before ESWL, 37 patients had unspecific abdominal symptoms (feeling of fullness and pressure, or slight pain, or both, in the right upper abdomen, flatulence, nausea, or food intolerance) and 63 patients had typical biliary symptoms (severe steady pain of more than 15 minutes and less than five hours duration in the right upper abdomen, in some cases radiating to the epigastrium or the back) either exclusively or with unspecific abdominal complaints. After becoming stone free, 72 of 100 patients lost the symptoms they had before treatment. All 28 patients with persisting symptoms had unspecific abdominal symptoms before treatment (exclusively unspecific symptoms and unspecific plus typical biliary symptoms). In contrast, patients with typical biliary symptoms before ESWL lost these in 95% of all cases. Although the anatomical structures are left intact after ESWL, the percentages of stone free patients with persisting symptoms are similar to those after cholecystectomy.
Appendicitis and Measles
Authors: P. L. Deshmukh
Journal: BMJ (1954)

<h3>Background</h3> There is a paucity of data on long-term management of type 1 autoimmune pancreatitis (AIP), a relapsing steroid-responsive disorder. <h3>Objective</h3> We describe our experience with treatment of relapses and maintenance of remission using steroid-sparing immunomodulators (IMs) and induction of remission using rituximab (RTX). <h3>Methods</h3> We obtained details of disease relapse and treatment in 116 type 1 AIP patients from clinic visits, medical records and telephone interviews. We compared relapse free survival in those treated with IMs versus those treated with steroids alone, assessed patients’ response to RTX, and identified treatment-related complications. <h3>Results</h3> During a median follow-up of 47 months, 52/116 AIP patients experienced 76 relapse episodes. The first relapse was treated with another course of steroids in 24 patients, and with steroids plus IM in another 27 patients; subsequent relapse-free survival until a second relapse was similar in the two groups (p=0.23). 38 patients received an IM for &gt;2 months; failure or intolerance of IM therapy occurred in 17 (45%). 12 patients with steroid or IM intolerance/resistance were treated with RTX, an antiCD20 antibody; 10 (83%) experienced complete remission and had no relapses while on maintenance therapy. Treatment-limiting side effects related to RTX were uncommon. <h3>Conclusions</h3> In type 1 AIP relapses are common. Relapse-free survival is similar in those treated with steroids plus IM compared to those treated with steroids alone. Nearly half the patients on IMs will relapse during treatment. RTX is effective in the treatment of both IM resistant and steroid intolerant patients.
Boehringer Ingelheim withdraws libido drug for women
Authors: J. Lenzer
Journal: BMJ (2010)

The German drug company Boehringer Ingelheim announced on 8 October that it is withdrawing from development its drug to increase female sexual desire.

The drug, flibanserin, which reduces serotonin concentrations while raising those of dopamine and noradrenaline (norepinephrine), was originally intended to be an antidepressant.

The company made the announcement after negative reviews by an advisory panel of the US Food and Drug Administration in June ( BMJ 2010;341:c3339 doi:10.1136/bmj.c3339) and a letter issued by the agency in August in response to the company’s new drug application.

Boehringer Ingelheim conducted several studies of the drug in North America …
Teichoic Acid Serologic Diagnosis of Staphylococcal Endocarditis
Authors: JOERG G. NAGEL
Journal: Annals of Internal Medicine (1975)

Using both double diffusion in agar and counterimmunoelectrophoresis, precipitating antibodies against staphylococcal teichoic acids were studied in 26 parenteral drug users with staphylococcal endocarditis at different times during their disease and in three control groups. The gel diffusion method was less sensitive (85% positive reactions in patients with endocarditis) but very specific (less than 5% false-positive reactions), whereas the more rapid (results in 40 minutes) counterimmunoelectrophoretic method was more sensitive (96% positive reactions in patients with endocarditis) and less specific (up to 10% false-positive reactions in drug-using controls). The use of both methods permits very accurate diagnostic differentiation between patients with endocarditis and "false-positives." Patients with staphylococcal endocarditis develop a prompt enough antibody response to be diagnostically helpful on admission to the hospital. With successful therapy over the ensuing weeks, the antibody titer declines and disappears. Some cross-reactions in patients with streptococcal endocarditis do occur.
Internal Iliac Artery Ligation in Obstetrics and Gynecology
Authors: Peter Siegel
Journal: JAMA (1961)

Ligation of the internal iliac arteries may be life-saving in the control of severe pelvic hemorrhage occurring spontaneously or operatively. This operation was done in 60 patients. It was unilateral in 15 and bilateral in 45. In addition, both ovarian arteries were ligated in 15 of the latter group, so that in these women all 4 vessels were ligated. Nevertheless, collateral circulation was adequate in all patients, and no sloughs followed. No deaths or serious complications resulted directly from the arterial ligation itself. Hemorrhage was effectively controlled in 53 of the women. Because of the effectiveness, simplicity, and safety of ligating the internal iliac artery, the operation deserves greater emphasis than it has received in the past.
A 9-factor score predicted 2-year risk for bleeding in outpatients with, or at high risk for, atherothrombosis
Authors: Alfonso Iorio
Journal: Annals of Internal Medicine (2010)

Source Citation Ducrocq G, Wallace JS, Baron G, et al; REACH Investigators. Risk score to predict serious bleeding in stable outpatients with or at risk of atherothrombosis. Eur Heart J. 2010;31:1257-65. 20181681
Predicting Patterns of Long-Term CD4 Reconstitution in HIV-Infected Children Starting Antiretroviral Therapy in Sub-Saharan Africa: A Cohort-Based Modelling Study
Authors: Marie-Quitterie Picat, Joanna Lewis, Victor Musiime, Andrew Prendergast, Kusum Nathoo, Addy Kekitiinwa, Patricia Nahirya Ntege, Diana M. Gibb, Rodolphe Thiebaut, A. Sarah Walker, Nigel Klein, Robin Callard
Journal: PLoS Medicine (2013)

Long-term immune reconstitution on antiretroviral therapy (ART) has important implications for HIV-infected children, who increasingly survive into adulthood. Children's response to ART differs from adults', and better descriptive and predictive models of reconstitution are needed to guide policy and direct research. We present statistical models characterising, qualitatively and quantitatively, patterns of long-term CD4 recovery.CD4 counts every 12 wk over a median (interquartile range) of 4.0 (3.7, 4.4) y in 1,206 HIV-infected children, aged 0.4-17.6 y, starting ART in the Antiretroviral Research for Watoto trial (ISRCTN 24791884) were analysed in an exploratory analysis supplementary to the trial's pre-specified outcomes. Most (n = 914; 76%) children's CD4 counts rose quickly on ART to a constant age-corrected level. Using nonlinear mixed-effects models, higher long-term CD4 counts were predicted for children starting ART younger, and with higher CD4 counts (p<0.001). These results suggest that current World Health Organization-recommended CD4 thresholds for starting ART in children ≥5 y will result in lower CD4 counts in older children when they become adults, such that vertically infected children who remain ART-naïve beyond 10 y of age are unlikely ever to normalise CD4 count, regardless of CD4 count at ART initiation. CD4 profiles with four qualitatively distinct reconstitution patterns were seen in the remaining 292 (24%) children. Study limitations included incomplete viral load data, and that the uncertainty in allocating children to distinct reconstitution groups was not modelled.Although younger ART-naïve children are at high risk of disease progression, they have good potential for achieving high CD4 counts on ART in later life provided ART is initiated following current World Health Organization (WHO), Paediatric European Network for Treatment of AIDS, or US Centers for Disease Control and Prevention guidelines. In contrast, to maximise CD4 reconstitution in treatment-naïve children >10 y, ART should ideally be considered even if there is a low risk of immediate disease progression. Further exploration of the immunological mechanisms for these CD4 recovery profiles should help guide management of paediatric HIV infection and optimise children's immunological development. Please see later in the article for the Editors' Summary.
Review: Preoperative smoking cessation interventions reduce postoperative complications
Authors: Andrea Truncali
Journal: Annals of Internal Medicine (2009)

ACP Journal Club20 October 2009Review: Preoperative smoking cessation interventions reduce postoperative complicationsAndrea Truncali, MD, MPH, Scott Sherman, MD, MPHAndrea Truncali, MD, MPHNew York University School of Medicine, New York, New York, USA (A.T., S.S.)Search for more papers by this author, Scott Sherman, MD, MPHNew York University School of Medicine, New York, New York, USA (A.T., S.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-151-8-200910200-02004 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationThomsen T, Tønnesen H, Moller AM. Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation. Br J Surg. 2009;96:451-61. https://pubmed.ncbi.nlm.nih.gov/19358172Clinical Impact RatingsGIM/FP/GP: Hospitalists: Pulmonology: References1 Floyd DL, Prentice-Dunn S, Rogers RW. A meta-analysis of research on protection motivation theory. Journal of Applied Social Psychology. 2000;30:407-29. Google Scholar2 Sørensen LT, Jørgensen S, Petersen LJ, et al. Acute effects of nicotine and smoking on blood flow, tissue oxygen, and aerobe metabolism of the skin and subcutis. J Surg Res. 2009;152:224-30. [PMID: 18468640] Google Scholar3 Lawrence VA, Cornell JE, Smetana GW; American College of Physicians. Strategies to reduce postoperative pulmonary complications after noncardiothoracic surgery: systematic review for the American College of Physicians. Ann Intern Med. 2006;144:596-608. [PMID: 16618957] Google Scholar Author, Article, and Disclosure InformationAffiliations: New York University School of Medicine, New York, New York, USA (A.T., S.S.)This article was published at Annals.org on 6 October 2009. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 October 2009Volume 151, Issue 8Page: JC4-4KeywordsMortalityNicotine replacement therapyNumber needed to treatPulmonary medicineRisk ratioSmoking cessationSurgeryThoracic surgeryWound healing ePublished: 20 October 2009 Issue Published: 20 October 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Focus: Brussels: Meddling or Benefiting: health in Europe?
Authors: R Watson
Journal: BMJ (1994)

Not so long ago discussion of health issues within the European Union was taboo: national governments insisted that the politically charged subject of health was their responsibility, not that of some supranational organisation. Yet the taboo is gradually disappearing.

It was ministers themselves at their meeting just before Christmas who specifically invited the European Commission to investigate the collection of blood and blood products and the search for self sufficiency - until recently a matter of national competence. The move was led by Germany, which is riding a political storm over contaminated blood, prompting cynics to suggest that Bonn simply wanted to pass its own national problem on to the union.

But less sceptical observers see the move as a natural development among the member states - who are increasingly cooperating over other …
Overadditive anti-tumoral effect of a combination of a histone deacetylase — and an angiogenesis inhibitor acts in rat hepatocellular carcinoma in vivo
Authors: C. Herold, M. Ganslmayer, M. Ocker, S. Zopf, G. Kraemer, E.G. Hahn, D. Schuppan
Journal: Journal of Hepatology (2003)
Mentalism, information, and consciousness
Authors: Richard A. Carlson
Journal: Behavioral and Brain Sciences (2002)

The target article addresses important empirical issues, but adopts a nonanalytic stance toward consciousness and presents the mentalistic view as a very radical position that rules out informational description of anything other than conscious mental states. A better mentalistic strategy is to show how the structure of some informational states is both constitutive of consciousness and necessary for psychological functions.
An Improved Technic of External Cardiac Compression in Infants and Young Children
Authors: Manning M. Thaler, George H. C. Stobie
Journal: New England Journal of Medicine (1963)

WE became aware of the dangers of external cardiac compression in infants and children when 2 cases of hepatic rupture came to our attention.1 A check through pathological files revealed that about 7 of 10 patients autopsied at the Hospital for Sick Children have received external cardiac compression terminally. A small but significant proportion sustain injuries associated with the procedure. Though mostly minor, trauma is occasionally extensive and in itself could cause death.These considerations prompted an investigation into the cause (or causes) and prevention of liver tear and rupture as the commonest serious complication of external cardiac compression in . . .
TRANSCATHETER AORTIC VALVE IMPLANTATION (TAVI) IMMEDIATELY IMPROVES GLOBAL LV SYSTOLIC AND DIASTOLIC FUNCTION
Authors: Per Halvorsen, Gry Dahle, Jan F. Bugge, Jan Hovdenes, Kjell A. Rein, Arnt Fiane, Bjørn Bendz, Lars Aaberge, Jacob Bergsland, Erik Fosse, Svend Aakhus
Journal: Journal of the American College of Cardiology (2011)
Warnings issued over COX 2 inhibitors in US and UK
Authors: Scott Gottlieb
Journal: BMJ (2004)

Warnings were issued last month about two COX 2 (cyclo-oxygenase-2) inhibitors because of fears that they might increase the risk of cardiovascular events, including heart attacks and strokes.

Celecoxib (Celebrex) showed an increased risk of cardiovascular events in a long term study (sponsored by the US National Cancer Institutes) that looked at use of the drug for prevention of colon cancer.

Patients in the five year trial taking 400 mg/day or 800 mg/day of celecoxib had, respectively, a 2.5-fold and 3.4-fold increased risk of a major cardiovascular event compared with placebo. The Food and Drug Administration and the National Cancer …
Hormonal Regulation of Human Growth
Authors: Matthew M. Rechler, S. Peter Nissley, Jesse Roth
Journal: New England Journal of Medicine (1987)

How does a human being reach normal adult height and weight? Inheritance sets the broad limits — to wit, the shortest elephant towers over the tallest mouse. Nutrition and other environmental factors, including the psychosocial, interact with a panoply of hormones and hormone-like substances and their receptors to bring a person to the full measure of his or her genetic destiny.Among the humoral agents, growth hormone (somatotropin) has long been known to have a pivotal role.1 A deficiency of pituitary growth hormone results in proportionate dwarfism that is responsive to treatment with growth hormone. It is now known, however, . . .
Insight into the pathogenesis of chronic lymphocytic leukemia (CLL) through analysis of IgVH gene usage and mutation status in familial CLL
Authors: Dalemari Crowther-Swanepoel, Ruth Wild, Gabrielle Sellick, Martin J. S. Dyer, Francesca R. Mauro, Robert J. G. Cuthbert, Viggo Jonsson, Estella Matutes, Claire Dearden, James Wiley, Stephen Fuller, Daniel Catovsky, Richard S. Houlston
Journal: Blood (2008)