tbuckley/cabot-search huggingface dataset:
Primaquine Failure and Cytochrome P-450 2D6 in <i>Plasmodium vivax</i> Malaria
Authors: Jason W. Bennett, Brandon S. Pybus, Anjali Yadava, Donna Tosh, Jason C. Sousa, William F. McCarthy, Gregory Deye, Victor Melendez, Christian F. Ockenhouse
Journal: New England Journal of Medicine (2013)

Primaquine is used to eradicate the hepatic or hypnozoite form of Plasmodium vivax that may lead to relapse of infection. Host genetic factors may play a role in the activity of primaquine therapy.
Abstract 3522: Pre-treatment with FSH enhances the ability of EP-100 to target and destroy human pancreatic cancer cells
Authors: Rajasree Solipuram, Sita Aggarwal, Carola Leuschner, Hector Alila, William Hansel
Journal: Cancer Research (2011)

Abstract The expression of luteinizing hormone releasing hormone (LHRH) receptors by pancreatic cancer cells has been clearly established. We observed that pancreatic cancer cell lines contain different numbers of LHRH receptors (BxPC3&amp;gt;MIAPaCa-2&amp;gt;PANC-1) using relative quantitation of RNA by real time PCR. In an in vitro study, we found that treatment of PANC-1 cells in culture with small amounts (10 or 30 ng/ml) of follicle stimulating hormone (FSH) caused a 3-fold increase in LHRH receptor gene expression. Therefore, we hypothesized that pre-treatment of nude mice bearing PANC-1 tumor xenografts with FSH will increase the number of LHRH receptors which will enhance the ability of the EP-100 (LHRH conjugated lytic peptide) to target and destroy PANC-1 pancreatic cancer cells. Our main objective was to determine in vitro and in vivo if FSH enhances the efficacy of EP-100 in targeting and destroying PANC-1 cells. PANC-1 cells (5000/well) were pretreated with FSH (10 and 30 ng/mL) for 24 h followed by EP-100 (4 and 6 µM) for 24 h in a medium containing 0.2% Dextran charcoal treated serum. MTT cell viability assay results showed that pre-treatment of PANC-1 cells with FSH significantly (P&amp;lt;0.001) enhanced the cytotoxicity of EP-100. PANC-1 tumor xenograft bearing Athymic Balb/C nude mice (n=11) were treated with EP-100 (0.2 and 0.02 mg/kg), iv, once a week for three weeks with or without FSH pre-treatment, sc, (3 mg/kg for three days prior to administering the conjugate). The treatment groups included were baseline (sacrificed at the beginning of treatment), vehicle, FSH alone, EP-100 (0.02 mg/kg) alone, EP-100 (0.02mg/kg) with FSH, EP-100 (0.2 mg/kg) alone, EP-100 (0.2 mg/kg) with FSH. FSH pre-treatment significantly enhanced the ability of EP-100 (0.02 mg/kg – P&amp;lt;0.05 and 0.2 mg/kg – P&amp;lt;0.001 compared to baseline) to regress the growth of PANC-1 tumor xenografts in vivo. Histopathological evaluation revealed an increase in tumor necrosis in FSH pre-treated mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3522. doi:10.1158/1538-7445.AM2011-3522
A Comparison between Protoveratrine A and Protoveratrine B Orally in Arterial Hypertension
Authors: Bertram M. Winer
Journal: New England Journal of Medicine (1956)

DERIVATIVES of veratrum plants have been -^ shown to be useful agents in the management of hypertension1 2 3 4 5 6 and eclampsia.7 8 9 Mixtures of veratrum alkaloids have potent hypotensive and bradycrotic activity. The limiting factor in the clinical use of these drugs has been the narrow dosage range between hypotensive and emetic effects. By the intravenous route there has been a high degree of reproducibility of nonemetic hypotensive responses in individual patients. However, orally, considerable variability in response has been common, making the long-term use of these drugs difficult in some patients.Evidence that different veratrum alkaloids have differing pharmacolcgie effects10 has encouraged . . .
The Navigation Guide - evidence-based medicine meets environmental health: systematic review of nonhuman evidence for PFOA effects on fetal growth.
Authors: Erica Koustas, Juleen Lam, Patrice Sutton, Paula I. Johnson, Dylan Sloane Atchley, Saunak Sen, Karen A. Robinson, Daniel A. Axelrad, Tracey J. Woodruff
Journal: Environmental Health Perspectives (2014)

In contrast to current methods of expert-based narrative review, the Navigation Guide is a systematic and transparent method for synthesizing environmental health research from multiple evidence streams. The Navigation Guide was developed to effectively and efficiently translate the available scientific evidence into timely prevention-oriented action.We applied the Navigation Guide systematic review method to answer the question "Does fetal developmental exposure to perfluorooctanoic acid (PFOA) or its salts affect fetal growth in animals ?" and to rate the strength of the experimental animal evidence.We conducted a comprehensive search of the literature, applied prespecified criteria to the search results to identify relevant studies, extracted data from studies, obtained additional information from study authors, conducted meta-analyses, and rated the overall quality and strength of the evidence.Twenty-one studies met the inclusion criteria. From the meta-analysis of eight mouse gavage data sets, we estimated that exposure of pregnant mice to increasing concentrations of PFOA was associated with a change in mean pup birth weight of -0.023 g (95% CI: -0.029, -0.016) per 1-unit increase in dose (milligrams per kilogram body weight per day). The evidence, consisting of 15 mammalian and 6 nonmammalian studies, was rated as "moderate" and "low" quality, respectively.Based on this first application of the Navigation Guide methodology, we found sufficient evidence that fetal developmental exposure to PFOA reduces fetal growth in animals.
Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer
Authors: Elise Punkenburg, Tina Vogler, Maike Büttner, Kerstin Amann, Max Waldner, Raja Atreya, Benjamin Abendroth, Jonas Mudter, Susanne Merkel, Eike Gallmeier, Stefan Rose-John, Markus F Neurath, Kai Hildner
Journal: Gut (2015)

<h3>Objectives</h3> IBDs have an increased risk for development of colorectal cancer (CRC). Here, we aimed at the characterisation of the functional role of Th17-associated transcription factors in sporadic and colitis-associated colon cancer in vivo. <h3>Design</h3> We used mice deficient or transgenic for <i>the activating protein 1</i> family member <i>basic leucine zipper transcription factor ATF-like</i> (Batf) to evaluate the role of Th17 cells during sporadic and inflammation-induced colon carcinogenesis. We also studied the expression of Batf and RORγt in patients with IBD and CRC. <h3>Results</h3> Batf but not <i>retinoic acid-related orphan receptor γt</i>(RORγt) expression was significantly increased together with interleukin (IL) 23 expression in UC but not in Crohn9s disease (CD) tissue samples. In CRC also Batf but not RORγt expression was increased and its expression correlated with the IL-23 and IL-23 receptor (IL-23R) expression. Finally, Batf but not RORγt was coexpressed with IL-17a, IL-23R and IL-6 within CRC-infiltrating CD4<sup>+</sup> T cells. Functional studies in mice revealed that Batf-dependent T cells are crucial regulators of sporadic and inflammation-induced CRC. Colitis-associated Batf<sup>−/−</sup> tumours lacked IL-17a<sup>+</sup>IL-23R<sup>+</sup>IL-6<sup>+</sup>CD4<sup>+</sup> T cells, hence displaying characteristics reminiscent of human CRC-infiltrating CD4<sup>+</sup> T cells. Strikingly, Batf<sup>−/−</sup> tumours contained low IL-23 but high IL-17a expression levels. Tumour formation and intratumoral IL-23 expression could be restored by administration of Hyper-IL-6 consisting of IL-6 and soluble IL-6 receptor. <h3>Conclusions</h3> Batf-dependent IL-23R<sup>+</sup>IL-6<sup>+</sup>CD4<sup>+</sup> Th17 cells critically control IL-23 driven colitis-associated tumour formation and the progression of sporadic colon tumours. Batf-dependent IL-23R<sup>+</sup> T cells represent a potential future therapeutic target limiting CRC progression.
The Effect of Sequence Evolution on Protein Structural Divergence
Authors: Simon G. Williams, Simon C. Lovell
Journal: Molecular Biology and Evolution (2009)

The complex constraints imposed by protein structure and function result in varied rates of sequence and structural divergence in proteins. Analysis of sequence differences between homologous proteins can advance our understanding of structural divergence and some of the constraints that govern the evolution of these molecules. Here, we assess the relationship between amino acid sequence and structural divergence. Firstly, we demonstrate that the relationship between protein sequence and structural divergence is governed by a variety of evolutionary constraints, including solvent exposure and secondary structure. Secondly, although compensatory substitutions are widespread, we find many radical size-changing mutations that are not compensated by neighboring complementary changes. Instead, these noncompensated substitutions are mitigated by alteration of protein structure. These results suggest a combined mechanism of accommodating substitutions in proteins, involving both coevolution and structural accommodation. Such a mechanism can explain previously observed correlated substitutions of residues that are distant both in sequence and structure, allowing an integrated view of sequence and structural divergence of proteins.
Encephalitis Syndrome of Lymphocytic Choriomeningitis Virus Infection
Authors: K. K. Nayak, S. O. Waller, G. Kuppuswamy
Journal: BMJ (1964)

Plasma Amylase-McGowan and Wills MkCBAL IJISNAL such a history was present the surgeon was advised that the level should not be taken as evidence of uncomplicated acute pan- creatitis.In the remaining eight cases a correct diagnosis was made in six and laparotomy was performed on four (Cases 5, 8, 9, and 10), of which three survived and one died of a stroke; of the two not operated on, one (Case 12) was diagnosed as a mild uncomplicated afferent-loop obstruction and treated con- servatively with success, while the other (Case 6) was considered unfit for operation and died.In the two remaining cases (Nos.7 and 11) there was uncertainty about accepting this interpreta- tion of the amylase level ; in one there had been operative trauma to the pancreas, and both showed considerable initial improvement on intravenous fluids and antibiotics; operation was withheld, and both died of peritonitis.We believe that correct interpretation of the amylase level would have led to operation in six patients who died, and might have reduced the overall mortality from eight to three.Our interpretation of high amylase levels might have to be qualified if it were common for uncomplicated acute pancreatitis to occur after gastrectomy.We are not aware of such an occurrence in this hospital during the period under review.Warren (1951) described five cases, but in none was a plasmaamylase level of more than 1,000 units/ 100 ml.recorded, and in two there was perforation of the duodenal stump, supposedly the result of the pancreatitis ; in one other case (fatal) there was no confirmation of the diagnosis by laparotomy or necropsy.Dunphy et al. (1953) recorded three cases, but again none had a plasma-amylase level of over 1,000 units/100 ml., and two were found at necropsy to have peritonitis in the absence of any obvious leak.Burton et al. (1957) described five cases, but the
STENT FRACTURE, TASC II CD LESION AS RESTENOSIS FACTORS, AND CILOSTAZOL AS A NEGATIVE-RESTENOSIS FACTOR WITHIN A YEAR FOLLOWING NITINOL STENT IMPLANTATION IN THE SUPERFICIAL FEMORAL ARTERY
Authors: Osamu Iida, Msaaki Uematsu, Seiki Nagata, Yoshimitsu Soga, Hiroyoshi Yokoi, Masakiyo Nobuyoshi, Keisuke Hirano, Toshiya Muramatsu, Shinsuke Nanto
Journal: Journal of the American College of Cardiology (2010)
Central Nervous System Tuberculosis with the Acquired Immunodeficiency Syndrome and Its Related Complex
Authors: Eliahou Bishburg, Gnana Sunderam, Lee B. Reichman, Rajendra Kapila
Journal: Annals of Internal Medicine (1986)

Central nervous system tuberculosis occurred in three patients with the acquired immunodeficiency syndrome (AIDS) and seven patients with AIDS-related complex who were evaluated for 48 months. Nine patients were intravenous drug abusers and one was Haitian. Five patients had cerebral-ring-enhancing lesions and three had hypodense areas. The clinical spectrum included meningitis in two patients, multiple cerebral abscesses in one, and tuberculomas in four. All Mycobacterium tuberculosis isolates were sensitive to standard antituberculous drugs. All patients received treatment with isoniazid, rifampin, and pyrazinamide; six patients also received streptomycin. Three patients with AIDS died of opportunistic infection preceded by central nervous system tuberculosis. Among the patients with the AIDS-related complex, three improved with treatment, three were lost to follow-up, and one died. Tuberculosis should be considered in the differential diagnosis of central nervous system mass lesions in intravenous drug abusers with AIDS or AIDS-related complex. Because patients with tuberculosis can be cured, biopsy of accessible brain mass lesions should be mandatory. Preventive therapy may be indicated in drug abusers without disease.
Was There an Epidemic of Diabetes in Nonwhite Adolescents in Allegheny County, Pennsylvania?
Authors: Ingrid M Libman, Ronald E LaPorte, Dorothy Becker, Janice S Dorman, Allan L Drash, Lewis Kuller
Journal: Diabetes Care (1998)

OBJECTIVE To determine the incidence of IDDM in children aged &amp;lt; 20 years at diagnosis in Allegheny County, Pennsylvania, for the period from 1 January 1990 to 31 December 1994 and to compare the incidence between whites and nonwhites in the same area and for the same time period. RESEARCH DESIGN AND METHODS All new patients diagnosed between January 1990 and December 1994 who were aged &amp;lt; 20 years, on insulin, and residents of Allegheny County at diagnosis were identified from medical records of 23 hospitals in the Allegheny County area. To verify the completeness of the hospitals using the capture-recapture method, pediatricians and diabetologists were used as a secondary source. RESULTS A total number of 257 patients were identified. The overall age-standardized incidence rate was 16.7/100,000. Nonwhites had a slightly higher incidence (17.6/100,000) than whites (16.5/100,000). In the 15–19 years age-group, the incidence in nonwhites (30.4/100,000) was almost three times higher than that in white (11.2/100,000) and more than two times higher than that in the previous period (from 1985 to 1989) (13.8/100,000). CONCLUSIONS For the first time in the Allegheny County registry, and in any other registry, nonwhites showed a higher incidence of IDDM than whites. The high incidence in the 15–19 years age-group was responsible for this phenomenon. This epidemic of diabetes in adolescent nonwhites may be the result of a rising incidence of classical IDDM or another type of diabetes. Further studies using population-based registries are needed to determine whether this increase is being seen in other areas and other ethnic groups and to clarify the reasons for the increase in IDDM among blacks.
B-Type Natriuretic Peptide for the Evaluation of Volume Status in Elderly Postoperative Patients
Authors: Justin P. Wagner, Jonathan R. Hiatt
Journal: JAMA (2014)

A 92-year-old man presented with iron-deficiency anemia. Upon evaluation, guaiacpositive stools were found and follow-up colonoscopy revealed an invasive adenocarcinoma of the cecum. He was scheduled for a laparoscopic right hemicolectomy. Preoperative stress echocardiogram revealed no significant cardiac dysfunction. Immediately before surgery, sequential compression devices were placed on his legs to reduce the risk for venous thromboembolic disease. Following his uncomplicated operation, pulse oximetry showed oxygen desaturation requiring supplemental oxygen. The patient developed paroxysmal tachycardia on the third postoperative day. He had no chest pain or mental status alteration. On physical examination, his pulse was 130/min and irregularly irregular, blood pressure was 126/59 mm Hg, and breath sounds were diminished in bibasilar lung fields. The abdomen was soft and laparoscopy port sites were clean and free of erythema, blood, or exudate. A bedside 12-lead electrocardiogram showed atrial fibrillation with rapid ventricular response and no ST-segment elevation. Portable chest x-ray showed pulmonary edema. Laboratory values are shown in the Table.
Hypothermia in the Treatment of Acute Pancreatitis
Authors: Seaborn A. Roddenbery
Journal: JAMA (1967)

A hypothermic unit was used to reduce and control extreme hyperpyrexia in two patients with acute pancreatitis. Both survived. Recent experiences by others using hypothermia in the treatment of experimental pancreatitis give us a rational explanation for the good response in both patients. The encouraging results obtained with a hypothermic unit as a basic therapeutic modality in severe cases of pancreatitis warrant additional clinical trials.
Evaluation of the Efficacy and Tolerability of Nitrendipine in Reducing Both Pressure and Left Ventricular Mass in Hypertensive Type 2 Diabetic Patients
Authors: Roldano Scognamiglio, Romano Nosadini, Marco Marin, Stefano Nisti, Giuseppe Fasoli, Monica Palisi, Francesco Frigato, Flavio Virgili, Andrea Carraro, Gaetano Crepaldi
Journal: Diabetes Care (1997)

OBJECTIVE To evaluate the efficacy and tolerability of nitrendipine in comparison with captopril in hypertensive diabetic patients with left ventricular hypertrophy (LVH). RESEARCH DESIGN AND METHODS A total of 75 patients enrolled in this study presented stable type 2 diabetes (not treated with insulin) and mild-to-moderate hypertension with a left ventricular mass ≥ 75 g/m2 by two-dimensional echocardiography. After a 4-week washout period, 38 patients were assigned to treatment with captopril, and 37 patients to nitrendipine (random allocation). The duration of follow-up was 36 weeks. RESULTS Patients of both groups were similar with regard to the duration of diabetes and hypertension, systolic and diastolic blood pressure at rest, degree of LVH, metabolic control, and albumin excretion rate (AER). Both drugs were equally effective in reducing systolic and diastolic blood pressure (captopril: from 165 ± 13/100 ± 4 to 147 ± 11/87 ± 4 mmHg; nitrendipine: from 167 ± 17/100 ± 5 to 143 ± 9/86 ± 4 mmHg; P &amp;lt; 0.05) and in reversing LVH (nitrendipine: from 87 ± 2 to 81 ± 1 g/m2; captopril: from 89 ± 2 to 85 ± 2 g/m2; P = 0.0001). Neither the left ventricular end-diastolic volume index nor the left ventricular ejection fraction changed significantly during the treatment period. CONCLUSION Nitrendipine is as effective as captopril in reducing both systolic and diastolic blood pressure and in reversing LVH. Neither drug showed any negative side effects on fasting plasma glucose and glycated hemoglobin (HbA1c) levels, and both maintain constant AERs.
Abstract LB-101: The antiandrogen drug dutasteride sensitizes triple negative breast cancer cells to chemotherapy via HIF-1α / VEGF-signaling
Authors: Marie-Kristin von Wahlde, Carolin Huelsewig, Christian Ruckert, Martin Götte, Ludwig Kiesel, Cornelia Liedtke, Christof Bernemann
Journal: Cancer Research (2014)

Abstract Background: Triple negative breast cancer is characterized by a lack of expression of both estrogen and progesterone receptor as well as lack of amplification of HER2. Patients with triple negative breast cancer carry an unfavorable prognosis compared to other breast cancer subtypes given that endocrine or HER-2 targeted therapies are not effective, rendering chemotherapy the sole effective treatment option to date. In a previous work by Liedtke et al. ((Liedtke et al., Cancer Res 2009) we generated a list of genes, which showed higher expression in triple negative breast cancer and, in addition, are known to encode targets for known non-oncologic drugs. These gene products might represent targets for future therapies of triple negative breast cancer. Results: We could identify SRD5A1, which encodes the type-1 isoform of the steroid-5-alpha-reductase, showing a higher expression in triple negative breast cancer both in vivo and in vitro. Dutasteride is a dual blocker of both the type-1 and type-2 isoform of SRD5A1 and is indicated in the treatment of benign prostate hyperplasia. Treatment of triple negative breast cancer cell lines with dutasteride was associated with a dose-dependent decrease in cell viability, altered protein expression of VEGF and HIF-1α and increased chemosensitivity. Conclusion: Our results demonstrate that firstly, using differential gene expression analysis in clinically relevant breast cancer subtypes, potential new drug targets can be generated. Secondly, we identified the SRD5A1-corresponding anti androgenic drug dutasteride as a combinatorial therapeutic option besides standard chemotherapy in highly aggressive triple negative breast cancer. Citation Format: Marie-Kristin von Wahlde, Carolin Huelsewig, Christian Ruckert, Martin Götte, Ludwig Kiesel, Cornelia Liedtke, Christof Bernemann. The antiandrogen drug dutasteride sensitizes triple negative breast cancer cells to chemotherapy via HIF-1α / VEGF-signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-101. doi:10.1158/1538-7445.AM2014-LB-101
Smart cards the key to trustworthy health information systems
Authors: R. Neame
Journal: BMJ (1997)

Some 20 years after they were first developed, "smart cards" are set to play a crucial part in healthcare systems. Last year about a billion were supplied, mainly for use in the financial sector, but their special features make them of particular strategic importance for the health sector, where they offer a ready made solution to some key problems of security and confidentiality. This article outlines what smart cards are and why they are so important in managing health information. I discuss some of the unique features of smart cards that are of special importance in the development of secure and trustworthy health information systems. Smart cards would enable individuals' identities to be authenticated and communications to be secured and would provide the mechanisms for implementing strong security, differential access to data, and definitive audit trails. Patient cards can also with complete security carry personal details, data on current health problems and medications, emergency care data, and pointers to where medical records for the patient can be found. Provider cards can in addition carry authorisations and information on computer set up.
Sandoz and the Monitoring of Patients Receiving Clozapine-Reply
Authors: Gilbert Honigfeld
Journal: JAMA (1991)

In Reply. —  We appreciate Dr Benton's incisive letter, and we agree fully with his ultimate conclusion: Sandoz would like to rid itself of this controversy. But even more important, we would like to see clozapine reach more of the severely ill schizophrenics who have had no significant relief from crippling symptoms when treated with old-fashioned neuroleptic drugs. In recent months, we have done much to achieve both of those goals, while ensuring that the breakthrough of clozapine therapy remains available to the patients who so desperately need it, despite potentially fatal adverse reactions.  In December, we announced our intention to separate the monitoring of clozapine from sales of the drug itself. On January 14, we announced a new wholesale pricing policy for clozapine tablets to make certain that physicians, providers, funders, and patients understand that separation. We are engaged in discussions with providers and funders on criteria to determine