tbuckley/cabot-search huggingface dataset:
Cost-Effectiveness of Male Circumcision for HIV Prevention in a South African Setting
Authors: James G Kahn, Elliot Marseille, Bertran Auvert
Journal: PLoS Medicine (2006)

Background Consistent with observational studies, a randomized controlled intervention trial of adult male circumcision (MC) conducted in the general population in Orange Farm (OF) (Gauteng Province, South Africa) demonstrated a protective effect against HIV acquisition of 60%. The objective of this study is to present the first cost-effectiveness analysis of the use of MC as an intervention to reduce the spread of HIV in sub-Saharan Africa. Methods and Findings Cost-effectiveness was modeled for 1,000 MCs done within a general adult male population. Intervention costs included performing MC and treatment of adverse events. HIV prevalence was estimated from published estimates and incidence among susceptible subjects calculated assuming a steady-state epidemic. Effectiveness was defined as the number of HIV infections averted (HIA), which was estimated by dynamically projecting over 20 years the reduction in HIV incidence observed in the OF trial, including secondary transmission to women. Net savings were calculated with adjustment for the averted lifetime duration cost of HIV treatment. Sensitivity analyses examined the effects of input uncertainty and program coverage. All results were discounted to the present at 3% per year. For Gauteng Province, assuming full coverage of the MC intervention, with a 2005 adult male prevalence of 25.6%, 1,000 circumcisions would avert an estimated 308 (80% CI 189–428) infections over 20 years. The cost is $181 (80% CI $117–$306) per HIA, and net savings are $2.4 million (80% CI $1.3 million to $3.6 million). Cost-effectiveness is sensitive to the costs of MC and of averted HIV treatment, the protective effect of MC, and HIV prevalence. With an HIV prevalence of 8.4%, the cost per HIA is $551 (80% CI $344–$1,071) and net savings are $753,000 (80% CI $0.3 million to $1.2 million). Cost-effectiveness improves by less than 10% when MC intervention coverage is 50% of full coverage. Conclusions In settings in sub-Saharan Africa with high or moderate HIV prevalence among the general population, adult MC is likely to be a cost-effective HIV prevention strategy, even when it has a low coverage. MC generates large net savings after adjustment for averted HIV medical costs.
Exclusive breastfeeding and incident atopic dermatitis in childhood: a systematic review and meta-analysis of prospective cohort studies
Authors: Y.W. Yang, C.L. Tsai, C.Y. Lu
Journal: British Journal of Dermatology (2009)

Journal Article Exclusive breastfeeding and incident atopic dermatitis in childhood: a systematic review and meta‐analysis of prospective cohort studies Get access Y.W. Yang, Y.W. Yang Department of Dermatology, Taipei Medical University Hospital, No. 252 Wusing St, Sinyi District, Taipei City 110, Taiwan Correspondence: Ya‐Wen Yang. E‐mail: yawen12@yahoo.com.tw Search for other works by this author on: Oxford Academic Google Scholar C.L. Tsai, C.L. Tsai Department of Epidemiology, Harvard School of Public Health, Boston, MA, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar C.Y. Lu C.Y. Lu Dr Tseng Skin Clinic, Taipei, Taiwan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 161, Issue 2, 1 August 2009, Pages 373–383, https://doi.org/10.1111/j.1365-2133.2009.09049.x Published: 01 August 2009
The Stiff-Person Syndrome: An Autoimmune Disorder Affecting Neurotransmission of γ-Aminobutyric Acid
Authors: Lucien M. Levy, Marinos C. Dalakas, Mary Kay Floeter
Journal: Annals of Internal Medicine (1999)

The stiff-person syndrome, a rare and disabling disorder, is characterized by muscle rigidity and episodic spasms that involve axial and limb musculature. Continuous contraction of agonist and antagonist muscles caused by involuntary motor-unit firing at rest are the hallmark clinical and electrophysiologic signs of the disease. Except for global muscle stiffness, results of neurologic examination are usually normal. Results of conventional computed tomography and magnetic resonance imaging of the brain are also normal. The cause of the stiff-person syndrome is unknown; however, an autoimmune pathogenesis is suspected because of 1) the presence of antibodies against glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the synthesis of the inhibitory neurotransmitter γ-aminobutyric acid [GABA]; 2) the association of the disease with other autoimmune conditions; 3) the presence of various autoantibodies; and 4) a strong immunogenetic association. Anti-GAD antibodies, which are found in high titers in most patients, seem to be directed against conformational forms of GAD. New evidence suggests that these antibodies may be pathogenic because they interfere with the synthesis of GABA. In addition, a reduction in brain levels of GABA, which is prominent in the motor cortex, has been demonstrated with magnetic resonance spectroscopy in patients with the stiff-person syndrome. The stiff-person syndrome is clinically elusive but potentially treatable and should be considered in patients with unexplained stiffness and spasms. Drugs that enhance GABA neurotransmission, such as diazepam, vigabatrin, and baclofen, provide mild to modest relief of clinical symptoms. Immunomodulatory agents, such as steroids, plasmapheresis, and intravenous immunoglobulin, seem to offer substantial improvement. Results of an ongoing controlled trial will elucidate the role of these agents in the treatment of the disease.
DIET AND FATTY ACID DISTRIBUTION IN SUBCUTANEOUS FAT AND IN THE CHOLESTEROL-TRIGLYCERIDE FRACTION OF SERUM OF YOUNG INFANTS*
Authors: M. J. Sweeney, J. N. Etteldorf, L. J. Throop, D. L. Timma, E. L. Wrenn
Journal: Journal of Clinical Investigation (1963)

The purpose of this paper is to report the fatty acid distributon in subcutaneous fat and in the cho- lesterol-triglyceride fraction of serum (C-TG) of four groups of infants, each of whom received a different test diet during the first 2 months of life.The major variables in the test diets were: linoleic acid content (approximately 1.2 to 39.2 per cent of dietary fat) ; percentage of total calories de- rived from fat (approximately 35 to 50 per cent); main source of dietary protein (cow milk and soybean) ; and percentage of total calories derived from protein (approximately 9 to 19 per cent).The protein and lipoprotein electrophoretic patterns, total protein, total lipid, and fractional lipid concentrations in the sera of these same groups of infants were subjects of previous reports (1, 2). SUBJECTS, PROCEDURES, AND METHODSSubjects.The test subjects were full-term infants born at St. Joseph's Hospital in Memphis, Tennessee, and housed, until adoption or other disposition, in the nursery of St. Peter's Orphanage, Memphis.All infants were placed in the study as soon after birth as possible and in no instance later than the fifth day of life.Procedures.Four different test diets were employed, and the infants were divided into four groups accordingly.Once assigned to a test diet, each infant remained so until discharged from the study.The diets were fed to the infants in ad lib amounts.Diet I was derived entirely from animal sources.It included a 20 calories per ounce evaporated milk, water, and lactose formula deriving approximately 15 per cent of its calories from cow milk protein, 35 per cent from butter fat, and 50 per cent from lactose; meats (started at age 6 weeks) and 0.6 cc of supplement 1 containing * These studies were supported by U. S. Public Health * Values adjusted from those shown in Table I so as to total 100 per cent. 1)
Pseudohypoxaemia in a patient with acute leukaemia
Authors: S. Charoenratanakul, K. Loasuthi
Journal: Thorax (1997)

Patients with acute leukaemia may have spuriously low arterial oxygen tensions (PaO2). The markedly increased numbers of white blood cells in these patients rapidly consume dissolved plasma oxygen resulting in dramatically decreased PaO2 and calculated oxygen saturations. The case history is reported of a patient with a white blood count of 191 000/mm3 in whom multiple arterial blood gas measurements documented hypoxaemia out of proportion to the clinical picture. Pulse oximetry was used to confirm higher haemoglobin oxygen saturations and to establish the spuriously low plasma oxygen tensions in this patient.
Genetics, Expression, and Function of Idiotypes
Authors: Klaus Rajewsky, Toshitada Takemori
Journal: Annual Review of Immunology (1983)

In this article we speak about the network of idiotypes in the immune system. We start by defining the vocabulary we are going to use. We then discuss the structural basis of idiotypic determinants (i.e. antigenic determi­ nants on the antibody variable region; also called idiotopes) and of their complementary anti-idiotypic antibody binding sites (anti-idiotopes). Idi­ otopes and anti-idiotopes are encoded by antibody V, D, and J genes. The idiotypic repertoire thus reflects the repertoire of these genes as they are expressed, selected, and somatically modified in the immune system. The idiotypic repertoire, its genetic basis and its selection in ontogeny, is a main theme of the present view. This relates directly to the functional idiotypic network: Which rules do idiotypic interactions in the immune system follow and what is their physiological role? We will see that idiotypic interactions seem to be involved in the growth control of lymphocyte clones with defined receptor specificity and may thus be essential for the generation of a diverse system of interacting cells. They also stabilize the expression of a given receptor repertoire in active immune responses. Idiotypic interactions occur within the compartment ofB lymphocytes, but they also involve T cells. We discuss the crucial issue of whether or not recognition of B-cell idiotypes is one of the principles by which T cells are selected in the immune system. This article cannot deal with all facets of idiotypic research. We restrict ourselves largely to the discussion of experimental work in the mouse and, in particular, we do not discuss in any detail the role of idiotypic interac­ tions in regulatory T-cell circuits controlling immune responses. Detailed models of immunologic control through cell interactions have emerged from recent work in this field. We refer the disappointed reader to a few
Enteric glia protect against Shigella flexneri invasion in intestinal epithelial cells: a role for S-nitrosoglutathione
Authors: M. Flamant, P. Aubert, M. Rolli-Derkinderen, A. Bourreille, M. R. Neunlist, M. M. Mahe, G. Meurette, B. Marteyn, T. Savidge, J. P. Galmiche, P. J. Sansonetti, M. Neunlist
Journal: Gut (2010)

<h3>Background</h3> Enteric glial cells (EGCs) are important regulators of intestinal epithelial barrier (IEB) functions. EGC-derived <i>S</i>-nitrosoglutathione (GSNO) has been shown to regulate IEB permeability. Whether EGCs and GSNO protect the IEB during infectious insult by pathogens such as <i>Shigella flexneri</i> is not known. <h3>Methods</h3> <i>S flexneri</i> effects were characterised using in vitro coculture models of Caco-2 cells and EGCs (or GSNO), ex vivo human colonic mucosa, and in vivo ligated rabbit intestinal loops. The effect of EGCs on <i>S flexneri</i>-induced changes in the invasion area and the inflammatory response were analysed by combining immunohistochemical, ELISA and PCR methods. Expression of small G-proteins was analysed by western blot. Expression of ZO-1 and localisation of bacteria were analysed by fluorescence microscopy. <h3>Results</h3> EGCs significantly reduced barrier lesions and inflammatory response induced by <i>S flexneri</i> in Caco-2 monolayers. The EGC-mediated effects were reproduced by GSNO, but not by reduced glutathione, and pharmacological inhibition of pathways involved in GSNO synthesis reduced EGC protecting effects. Furthermore, expression of Cdc42 and phospho-PAK in Caco-2 monolayers was significantly reduced in the presence of EGCs or GSNO. In addition, changes in ZO-1 expression and distribution induced by <i>S flexneri</i> were prevented by EGCs and GSNO. Finally, GSNO reduced <i>S flexneri</i>-induced lesions of the IEB in human mucosal colonic explants and in a rabbit model of shigellosis. <h3>Conclusion</h3> These results highlight a major protective function of EGCs and GSNO in the IEB against <i>S flexneri</i> attack. Consequently, this study lays the scientific basis for using GSNO to reduce barrier susceptibility to infectious or inflammatory challenge.
Margaret McCartney: Don't blame us
Authors: M. McCartney
Journal: BMJ (2014)

We keep hearing diktats that we need a no-blame culture in the NHS.Don Berwick, the US healthcare quality supremo, has claimed that such a culture is safer for patients and leads to better care, but there doesn't seem to be much evidence of one. 1 We need an amnesty on mistakes, errors, screw-ups, and near disasters.The truth is that mistakes are normal; perfect care is not.Every normal day is full of near misses, many of the dangerously slow-burn kind.
Prognostic model to predict survival following first-line chemotherapy in patients with metastatic gastric adenocarcinoma
Authors: J. Lee, T. Lim, J.E. Uhm, K.W. Park, S.H. Park, S.C. Lee, J.O. Park, Y.S. Park, H.Y. Lim, T.S. Sohn, J.H. Noh, J.S. Heo, C.K. Park, S. Kim, W.K. Kang
Journal: Annals of Oncology (2007)
Molecular Pathways: MERTK Signaling in Cancer
Authors: Christopher T. Cummings, Deborah DeRyckere, H. Shelton Earp, Douglas K. Graham
Journal: Clinical Cancer Research (2013)

MERTK is a receptor tyrosine kinase of the TAM (Tyro3, Axl, MERTK) family, with a defined spectrum of normal expression. However, MERTK is overexpressed or ectopically expressed in a wide variety of cancers, including leukemia, non-small cell lung cancer, glioblastoma, melanoma, prostate cancer, breast cancer, colon cancer, gastric cancer, pituitary adenomas, and rhabdomyosarcomas, potentially resulting in the activation of several canonical oncogenic signaling pathways. These include the mitogen-activated protein kinase and phosphoinositide 3-kinase pathways, as well as regulation of signal transducer and activator of transcription family members, migration-associated proteins including the focal adhesion kinase and myosin light chain 2, and prosurvival proteins such as survivin and Bcl-2. Each has been implicated in MERTK physiologic and oncogenic functions. In neoplastic cells, these signaling events result in functional phenotypes such as decreased apoptosis, increased migration, chemoresistance, increased colony formation, and increased tumor formation in murine models. Conversely, MERTK inhibition by genetic or pharmacologic means can reverse these pro-oncogenic phenotypes. Multiple therapeutic approaches to MERTK inhibition are currently in development, including ligand "traps", a monoclonal antibody, and small-molecule tyrosine kinase inhibitors.
Malignant colorectal polyps: venous invasion and successful treatment by endoscopic polypectomy.
Authors: J M Geraghty, C B Williams, I C Talbot
Journal: Gut (1991)

We reviewed the pathology of 81 malignant colorectal polyps in 80 patients treated by endoscopic polypectomy and assessed the importance of carcinomatous invasion of veins in the stalk (submucosa). All the patients were followed up for at least five years. Venous invasion was present in 30 of the polyps (37%). The histological features of lymphatic invasion were considered too subjective to be of value. Most of the tumours were well or moderately differentiated adenocarcinomas, one was poorly differentiated, and one was a signet ring cell carcinoma. Seventy one patients were treated by polypectomy alone, and 58 of these were alive and well five years later, with no evidence of recurrence. Nine died of unrelated causes within five years, but four died of carcinomatosis: one with recurrent tumour, one with a possible metachronous caecal cancer, and in two patients there was late development of malignancy of uncertain nature. The remaining nine patients underwent surgical resection after initial endoscopic polypectomy because of incompleteness of excision, poor differentiation of the tumour, or a decision by the surgeon. Tumour was not present in the resection specimens apart from a single lymph node deposit in the patient with signet ring cell carcinoma. These nine patients were alive and well without evidence of recurrence five years later. The results reemphasize the necessity of good cooperation between endoscopist and pathologist, meticulous laboratory technique, strict histopathological criteria including examination of resection margins and degree of differentiation of the tumour, and regular endoscopic follow up. Endoscopic polypectomy of pedunculated and sessile malignant polyps is adequate treatment if the lesion can be removed in one piece, the tumour is well or moderately differentiated, and local excision is judged complete by endoscopic and histological criteria. Patients with histologically incompletely excised polyps, containing well or moderately differentiated carcinoma, can be safely managed by conservative treatment provided the endoscopist is certain there is no residual tumour. Venous invasion by tumour is a common finding in malignant colorectal polyps and seems to have no prognostic importance.
Development of β-Lapachone Prodrugs for Therapy Against Human Cancer Cells with Elevated NAD(P)H:Quinone Oxidoreductase 1 Levels
Authors: Kathryn E. Reinicke, Erik A. Bey, Melissa S. Bentle, John J. Pink, Stephen T. Ingalls, Charles L. Hoppel, Rosana I. Misico, Gisela M. Arzac, Gerardo Burton, William G. Bornmann, Damon Sutton, Jinming Gao, David A. Boothman
Journal: Clinical Cancer Research (2005)

Abstract β-Lapachone, an o-naphthoquinone, induces a novel caspase- and p53-independent apoptotic pathway dependent on NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 reduces β-lapachone to an unstable hydroquinone that rapidly undergoes a two-step oxidation back to the parent compound, perpetuating a futile redox cycle. A deficiency or inhibition of NQO1 rendered cells resistant to β-lapachone. Thus, β-lapachone has great potential for the treatment of specific cancers with elevated NQO1 levels (e.g., breast, non–small cell lung, pancreatic, colon, and prostate cancers). We report the development of mono(arylimino) derivatives of β-lapachone as potential prodrugs. These derivatives are relatively nontoxic and not substrates for NQO1 when initially diluted in water. In solution, however, they undergo hydrolytic conversion to β-lapachone at rates dependent on the electron-withdrawing strength of their substituent groups and pH of the diluent. NQO1 enzyme assays, UV-visible spectrophotometry, high-performance liquid chromatography-electrospray ionization-mass spectrometry, and nuclear magnetic resonance analyses confirmed and monitored conversion of each derivative to β-lapachone. Once converted, β-lapachone derivatives caused NQO1-dependent, μ-calpain-mediated cell death in human cancer cells identical to that caused by β-lapachone. Interestingly, coadministration of N-acetyl-l-cysteine, prevented derivative-induced cytotoxicity but did not affect β-lapachone lethality. Nuclear magnetic resonance analyses indicated that prevention of β-lapachone derivative cytotoxicity was the result of direct modification of these derivatives by N-acetyl-l-cysteine, preventing their conversion to β-lapachone. The use of β-lapachone mono(arylimino) prodrug derivatives, or more specifically a derivative converted in a tumor-specific manner (i.e., in the acidic local environment of the tumor tissue), should reduce normal tissue toxicity while eliciting tumor-selective cell killing by NQO1 bioactivation.
Drug‐specific <i>in vitro</i> release of IL‐2, IL‐5, IL‐13 and IFN‐γ in patients with delayed‐type drug hypersensitivity
Authors: P. Lochmatter, A. Beeler, T. T. Kawabata, B. O. Gerber, W. J. Pichler
Journal: Allergy (2009)

The most prevalent drug hypersensitivity reactions are T-cell mediated. The only established in vitro test for detecting T-cell sensitization to drugs is the lymphocyte transformation test, which is of limited practicability. To find an alternative in vitro method to detect drug-sensitized T cells, we screened the in vitro secretion of 17 cytokines/chemokines by peripheral blood mononuclear cells (PBMC) of patients with well-documented drug allergies, in order to identify the most promising cytokines/chemokines for detection of T-cell sensitization to drugs.Peripheral blood mononuclear cell of 10 patients, five allergic to beta-lactams and five to sulfanilamides, and of five healthy controls were incubated for 3 days with the drug antigen. Cytokine concentrations were measured in the supernatants using commercially available 17-plex bead-based immunoassay kits.Among the 17 cytokines/chemokines analysed, interleukin-2 (IL-2), IL-5, IL-13 and interferon-gamma (IFN-gamma) secretion in response to the drugs were significantly increased in patients when compared with healthy controls. No difference in cytokine secretion patterns between sulfonamide- and beta-lactam-reactive PBMC could be observed. The secretion of other cytokines/chemokines showed a high variability among patients.The measurement of IL-2, IL-5, IL-13 or IFN-gamma or a combination thereof might be a useful in vitro tool for detection of T-cell sensitization to drugs. Secretion of these cytokines seems independent of the type of drug antigen and the phenotype of the drug reaction. A study including a higher number of patients and controls will be needed to determine the exact sensitivity and specificity of this test.
Perioperative Beta-Blocker Therapy and Mortality after Major Noncardiac Surgery
Authors: Peter K. Lindenauer, Penelope Pekow, Kaijun Wang, Dheeresh K. Mamidi, Benjamin Gutierrez, Evan M. Benjamin
Journal: New England Journal of Medicine (2005)

Despite limited evidence from randomized trials, perioperative treatment with beta-blockers is now widely advocated. We assessed the use of perioperative beta-blockers and their association with in-hospital mortality in routine clinical practice.We conducted a retrospective cohort study of patients 18 years of age or older who underwent major noncardiac surgery in 2000 and 2001 at 329 hospitals throughout the United States. We used propensity-score matching to adjust for differences between patients who received perioperative beta-blockers and those who did not receive such therapy and compared in-hospital mortality using multivariable logistic modeling.Of 782,969 patients, 663,635 (85 percent) had no recorded contraindications to beta-blockers, 122,338 of whom (18 percent) received such treatment during the first two hospital days, including 14 percent of patients with a Revised Cardiac Risk Index (RCRI) score of 0 and 44 percent with a score of 4 or higher. The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk; among the 580,665 patients with an RCRI score of 0 or 1, treatment was associated with no benefit and possible harm, whereas among the patients with an RCRI score of 2, 3, or 4 or more, the adjusted odds ratios for death in the hospital were 0.88 (95 percent confidence interval, 0.80 to 0.98), 0.71 (95 percent confidence interval, 0.63 to 0.80), and 0.58 (95 percent confidence interval, 0.50 to 0.67), respectively.Perioperative beta-blocker therapy is associated with a reduced risk of in-hospital death among high-risk, but not low-risk, patients undergoing major noncardiac surgery. Patient safety may be enhanced by increasing the use of beta-blockers in high-risk patients.