tbuckley/cabot-search huggingface dataset:
How easily malaria can be missed
Authors: Philip J Allan, Hasan I S Tahir
Journal: Journal of the Royal Society of Medicine (2006)

The diagnosis of malaria can be missed when there is a significant time lag from exposure and negative initial tests. As clinicians we must always consider the diagnosis in the appropriate clinical setting as a missed diagnosis can potentially result in serious consequences.

A 27-year-old Nigerian woman presented with a 2-day history of headaches, mild photophobia, sweats and fever. She arrived in the UK from Nigeria 8 months previously and had not been back since. On admission she was unwell with a temperature of 38.5°C, pulse 110/min but otherwise haemodynamically stable. Examination revealed a soft ejection systolic murmur and signs of meningism, but her neurological assessment was otherwise entirely normal. Her initial investigations showed a haemoglobin level of 11.8 g/dL, white cell count 3.9×109/L, lymphocytes 0.5×109/L, platelets 118×109/L, C-reactive protein 121 mg/L; urea and electrolytes and liver function tests were normal.

She was commenced on ceftriaxone 2 g daily with a presumptive diagnosis of meningitis. The patient had a normal computerized tomograph of the head, which was followed by a normal lumbar puncture. Two sets of blood cultures and a mid-stream urine sample had no growth after 48 h. The initial admission pyrexic thick and thin blood film and malarial antigen test (Optimal, DiaMed) were negative.

She improved initially with antibiotics and intravenous fluids. 24 h into her admission, having been reviewed by a number of senior doctors, her working diagnosis was changed to one of a viral illness and plans were made for her discharge. Malaria was felt to be unlikely given that not only was she 8 months post-exposure for malaria, her blood film and antigen test were negative.

However, on the day of discharge she was found to spike a temperature of 38°C and remained thrombocytopenic (108×109/L). It was decided that in view of her country of origin and the fact that she remained thrombocytopenic, malaria still needed to be considered. Even though a thick and thin blood film and malarial antigen test (Optimal, DiaMed) were negative, we felt three negative blood films were needed before excluding malaria and labelling her as a patient with a viral illness.

Interestingly, a repeat blood film showed malarial parasitaemia of 5% Plasmodium falciparum (Figure 1). Her haemoglobin dropped to 9 g/dL and platelets dropped to 93×109/L over the next 2 days, which then recovered. She was treated with intravenous quinine (10 mg/kg) for 48 h and converted to oral quinine for 7 days followed by three tablets of oral pyrimethamine with sulfadoxine (Fansidar). She was discharged home with a negative parasitaemia.



Figure 1

Patients blood film showing malarial parasites (in colour online)
Production of Enhanced Immunity to Autologous Material by Means of Coupling to an Antigenic Protein Carrier.
Authors: Jack Shapiro
Journal: Annals of Internal Medicine (1965)

s1 May 1965Production of Enhanced Immunity to Autologous Material by Means of Coupling to an Antigenic Protein Carrier.Jack Shapiro, M.D., Chiyo Chiba, M.D., Norbert Czaikowski, M.D., Frederick Cushing, M.D., Melvyn Rosenblatt, M.S., Paul L. Wolf, M.D., Richard J. Bing, M.D., F.A.C.P.Jack Shapiro, M.D.Search for more papers by this author, Chiyo Chiba, M.D.Search for more papers by this author, Norbert Czaikowski, M.D.Search for more papers by this author, Frederick Cushing, M.D.Search for more papers by this author, Melvyn Rosenblatt, M.S.Search for more papers by this author, Paul L. Wolf, M.D.Search for more papers by this author, Richard J. Bing, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-5-1090_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe possibility was explored of establishing a state of active immunity by means of coupling components of autologous body material to an antigenic protein carrier and injecting this complex into the same host from which the material was obtained. Antigenicity of autologous material was produced by diazotization of autologous material with a foreign protein according to the method of Landsteiner. The autologous material thus acted as a haptene and elicited antibodies directed against the same tissue of the same animal. For example, to produce antibodies against the animal's own lymphocytes, lymphoid cells of a dog were coupled to human gamma... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Detroit, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1965Volume 62, Issue 5Page: 1090-1090KeywordsAntibodiesAntigensImmunityLymphocytesProteins Issue Published: 1 May 1965 PDF DownloadLoading ...
If Your Child Is Hospitalized: The Hospital Health Care Team
Authors: Megan A. Moreno, Frederick P. Rivara
Journal: JAMA Pediatrics (2013)

If Your Child Is Hospitalized:The Hospital Health Care Team I f your child needs to be in the hospital, it can be a stressful and confusing experience.In many hospitals, there are multiple people involved in the care of each pediatric patient, and it can be challenging for parents to keep track of who is who.I outline the typical medical and nursing team members, and suggest ways to interact with your child's hospital health care team.
Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer
Authors: Yumi Yamamoto, Richard B. Gaynor
Journal: Journal of Clinical Investigation (2001)

NF-κB comprises a family of inducible transcription factors that serve as important regulators of the host immune and inflammatory response. In addition, NF-κB is also involved in protecting cells from undergoing apoptosis in response to DNA damage or cytokine treatment. Stimulation of the NF-κB pathway is mediated by diverse signal transduction cascades. These signals activate the IκB kinases, IKKα and IKKβ, which phosphorylate inhibitory proteins known as IκB to result in their ubiquitination and degradation by the proteasome. The degradation of IκB results in the translocation of NF-κB from the cytoplasm to the nucleus where it activates the expression of specific cellular genes. As we better understand the regulation of the NF-κB pathway, the potential for inhibiting this pathway has received attention. Agents that inhibit this pathway, such as glucocorticoids and aspirin, can reduce the inflammatory response, while other agents such as dominant negative IκB proteins potentiate the effects of chemotherapy and radiation therapy in the treatment of cancer. Here, we discuss cellular genes and disease states associated with activation of the NF-κB pathway and consider therapeutic strategies to prevent the prolonged activation of the NF-κB pathway.
Disorders of Mental Status: Dementia, Encephalopathy, Coma, Syncope
Authors: Daniel B. Hier
Journal: Annals of Internal Medicine (1998)

Medical Writings15 August 1998Disorders of Mental Status: Dementia, Encephalopathy, Coma, SyncopeDaniel B. Hier, MDDaniel B. Hier, MDUniversity of Illinois at Chicago College of Medicine, Chicago, IllinoisSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-4-199808150-00031 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Disorders of Mental Status: Dementia, Encephalopathy, Coma, Syncope; Misulis KE. 303 pages. Boston: Butterworth-Heinemann; 1998. $40.00. ISBN 0750699884. Order phone 800-366-2665.Field of medicine: Neurology.Format: Softcover book.Audience: Neurologists and internists.Purpose: To facilitate the diagnosis and management of mental status disorders.Content: This pocket-sized book is divided into three sections that cover evaluation of mental status, disorders of mental status, and management issues. The section on disorders of mental status addresses four major clinical presentations: coma, encephalopathy, syncope, and dementia. In this context, the author reviews the effects of hypoxia, stroke, metabolic disorders, seizures, hydrocephalus, and degenerative disease.... Author, Article, and Disclosure InformationAffiliations: University of Illinois at Chicago College of Medicine, Chicago, Illinois PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1998Volume 129, Issue 4Page: 340KeywordsBrain diseasesComaDementiaEpileptic seizuresHydrocephalusHypoxiaMetabolic disordersNeurologyStrokeSyncope ePublished: 15 August 2000 Issue Published: 15 August 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Link between pollution and asthma uncovered
Authors: T. Sheldon
Journal: BMJ (1999)

Dutch researchers have uncovered elusive evidence of a direct link between air pollution and children's asthma symptoms by first identifying groups at risk, such as children with allergies.

In research done at Groningen University, which was published last week (Lancet 1999;353:874-8), children with both bronchial hyperresponsiveness and atopy, a susceptibility to allergens measured by higher concentrations of IgE antibodies, were for the first time compared with children from control groups.

The researchers found that as concentrations of …
In vivo targeting of acoustically reflective liposomes for intravascular and transvascular ultrasonic enhancement
Authors: Sasha M. Demos, Hayat Alkan-Onyuksel, Bonnie J. Kane, Kishin Ramani, Ashwin Nagaraj, Rodney Greene, Melvin Klegerman, David D. McPherson
Journal: Journal of the American College of Cardiology (1999)
Two Distinct Pathways of Immuno-Modulation Improve Potency of p53 Immunization in Rejecting Established Tumors
Authors: Pirouz Daftarian, Guang-Yun Song, Saima Ali, Moshe Faynsod, Jeff Longmate, Don J. Diamond, Joshua D. I. Ellenhorn
Journal: Cancer Research (2004)

Abstract The p53 gene product is overexpressed by almost 50% of cancers, making it an ideal target for cancer immunotherapy. We previously demonstrated rejection of established p53-overexpressing tumors without stimulating autoimmunity by immunization with modified vaccinia Ankara-expressing murine p53 (MVAp53). Tumor rejection was enhanced through antibody-mediated CTL-associated antigen 4 (CTLA-4) blockade. We examined the role of synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine-phosphate-guanine (CpG) motifs (CpG ODN) in enhancing MVAp53-mediated tumor rejection. CpG ODN with MVAp53 resulted in tumor rejection in BALB/c mice bearing poorly immunogenic 11A-1 murine mammary carcinomas or Meth A sarcomas and C57Bl/6 mice bearing MC-38 colon carcinomas. The effect was similar to that seen in tumor-bearing mice treated with MVAp53 along with CTLA-4 blockade. Monoclonal antibody depletion experiments demonstrated that the adjuvant effects of CpG ODN and CTLA-4 blockades were CD8 dependent. CpG ODN were partially natural killer cell dependent and ineffective in Toll-like Receptor 9−/− and interleukin 6−/− mice, whereas CTLA-4 blockade was partially CD4 dependent and functional in Toll-like Receptor 9−/− and interleukin 6−/− mice. In addition, when administered with MVAp53, both adjuvants enhanced p53-specific cytotoxicity and demonstrated an additive effect when combined. The combination of CpG ODN and CTLA-4 blockade worked synergistically to reject palpable 11A-1 and MC-38 tumors. These experiments demonstrate the potential for augmenting MVAp53-mediated antitumor immunity using CpG ODN and CTLA-4 blockade. This cell-free immunotherapy approach is a candidate for evaluation in cancer patients.
Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs.
Authors: Lennart Eriksson, Joanna Jaworska, Andrew P Worth, Mark T D Cronin, Robert M McDowell, Paola Gramatica
Journal: Environmental Health Perspectives (2003)

This article provides an overview of methods for reliability assessment of quantitative structure-activity relationship (QSAR) models in the context of regulatory acceptance of human health and environmental QSARs. Useful diagnostic tools and data analytical approaches are highlighted and exemplified. Particular emphasis is given to the question of how to define the applicability borders of a QSAR and how to estimate parameter and prediction uncertainty. The article ends with a discussion regarding QSAR acceptability criteria. This discussion contains a list of recommended acceptability criteria, and we give reference values for important QSAR performance statistics. Finally, we emphasize that rigorous and independent validation of QSARs is an essential step toward their regulatory acceptance and implementation.
Cavitary Pulmonary Lymphosarcoma Masquerading as Rheumatoid Lung Disease
Authors: Steven A. Sahn
Journal: JAMA (1976)

WE PRESENT the case of a woman with rheumatoid disease and bilateral infiltrates progressing to cavitary lung disease, subsequently diagnosed as lymphosarcoma of the lung. The purpose of this report is to remind the reader of this rare entity.  Report of a Case  A 46-year-old woman was first hospitalized at Denver General Hospital in April 1971, with a diagnosis of nonresolving bilateral pulmonary infiltrates (Fig 1). In April 1970, she had had the onset of morning stiffness, particularly in the fingers and wrists. These symptoms were progressive over the next year.  On admission to the hospital, she had bilateral lower-lung-zone inspiratory rales and bronchovesicular breath sounds. Swelling, tenderness, and mild erythema of the proximal interphalangeal joints of both hands were present. The wrists and ankles showed evidence of mild synovitis. No subcutaneous nodules, lymphadenopathy, or splenomegaly were noted.  Laboratory values were as follows: hematocrit, 35 vol%; white blood cells, 6,500/cu
Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia
Authors: L N Brandao, A Winges, S Christoph, S Sather, J Migdall-Wilson, J Schlegel, A McGranahan, D Gao, X Liang, D DeRyckere, D K Graham
Journal: Blood Cancer Journal (2013)

Pediatric leukemia survival rates have improved dramatically over the past decades. However, current treatment protocols are still largely ineffective in cases of relapsed leukemia and are associated with a significant rate of chronic health conditions. Thus, there is a continued need for new therapeutic options. Here, we show that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic leukemia (T-ALL) cell lines. Stimulation of MerTK by the ligand Gas6 led to activation of the prosurvival proteins Erk 1/2 and Stat5, and MerTK-dependent activation of the STAT pathway in leukemia represents a novel finding. Furthermore, inhibition of MerTK expression increased the sensitivity of T-ALL cells to treatment with chemotherapeutic agents and decreased the oncogenic potential of the Jurkat T-ALL cell line in a methylcellulose colony-forming assay. Lastly, inhibition of MerTK expression significantly increased median survival in a xenograft mouse model of leukemia (30.5 days vs 60 days, P<0.0001). These results suggest that inhibition of MerTK is a promising therapeutic strategy for the treatment of leukemia and may allow for dose reduction of currently used chemotherapeutics resulting in decreased rates of therapy-associated toxicities.
Points: Is schizophrenia a neurodevelopmental disorder?
Authors: S J Cooper, D J King
Journal: BMJ (1987)

<h3>Background</h3> Compared with traditional screening questionnaires, computerised adaptive tests for severity of depression (CAT-DI) and computerised adaptive diagnostic modules for depression (CAD-MDD) show improved precision in screening for major depressive disorder. CAT measures have been tailored to perinatal women but have not been studied in low-income women of colour despite high rates of perinatal depression (PND). <h3>Objective</h3> This study aimed to examine the concordance between CAT and traditional measures of depression in a sample of primarily low-income black and Latina women. <h3>Methods</h3> In total, 373 women (49% black; 29% Latina) completed the Patient Health Questionnaire-9 (PHQ-9), CAD-MDD and CAT-DI at 845 visits across pregnancy and postpartum. We examined the concordance between continuous CAT-DI and PHQ-9 scores and between binary measures of PND diagnosis on CAD-MDD and the PHQ-9 (cut-off score &gt;10). We examined cases with a positive PND diagnosis on the CAD-MDD but not on the PHQ-9 (‘missed’ cases) to determine whether clinic notes were consistent with CAD-MDD results. <h3>Findings</h3> CAT-DI and PHQ-9 scores were significantly associated (concordance correlation coefficient=0.67; 95% CI 0.58 to 0.74). CAD-MDD detected 5% more case of PND compared with PHQ-9 (p&lt;0.001). The average per-visit rate of PND was 14.4% (14.5% in blacks, 14.9% in Latinas) on the CAD-MDD, and 9.5% (9.8% in blacks, 8.8% in Latinas) on the PHQ-9. Clinical notes were available on 60% of ‘missed’ cases and validated CAD-MDD PND diagnosis in 89% of cases. <h3>Conclusions</h3> CAD-MDD detected 5% more cases of PND in women of colour compared with traditional tests, and the majority of these cases were verified by clinician notes. <h3>Clinical implications</h3> Use of CAT in routine clinic care may address health disparities in PND screening.
Continuous Aspiration of Subglottic Secretions in Preventing Ventilator-Associated Pneumonia
Authors: Jordi Valles
Journal: Annals of Internal Medicine (1995)

Objective: To determine whether continuous subglottic aspiration prevents nosocomial pneumonia in mechanically ventilated patients. Design: A randomized, controlled, blinded study. Setting: Medical-surgical intensive care unit. Patients: 190 patients who were admitted to the intensive care unit during a 33-month period and whose condition suggested the need for prolonged intubation (>3 days). Intervention: 76 patients were randomly allocated to receive continuous aspiration of subglottic secretions, and 77 control patients were allocated to receive usual care. Measurements: The numbers of cases of ventilator-associated pneumonia, ventilated days, days in intensive care unit, and deaths were recorded. The amount of subglottic secretions aspirated daily and surveillance cultures in the subglottic secretions were also obtained periodically. Etiologic diagnosis was based on the quantitative culture of secretions obtained by protected specimen brush or bronchoalveolar lavage. Results: The incidence rate of ventilator-associated pneumonia was 19.9 episodes/1000 ventilator days in the patients receiving continuous aspiration of subglottic secretions and 39.6 episodes/1000 ventilator days in the control patients (relative risk, 1.98; 95% CI, 1.03 to 3.82). This difference was due to a significant (P < 0.03) reduction in the number of gram-positive cocci and Haemophilus influenzae organisms in the patients receiving continuous aspiration. However, no differences were observed in the number of Pseudomonas aeruginosa or Enterobacteriaceae organisms. Episodes of ventilator-associated pneumonia occurred later in patients receiving continuous aspiration (12.0 ± 7.1 days) than in the control patients (5.9 ± 2.1 days) (P = 0.003). The same microorganisms isolated from protected specimen brush or bronchoalveolar lavage cultures in patients with ventilator-associated pneumonia were previously isolated from cultures of subglottic secretions in 85% of cases. No significant differences in outcome were found. Conclusions: The incidence of nosocomial pneumonia in mechanically ventilated patients can be significantly reduced by using a simple method that decreases the chronic microaspirations through the cuff of endotracheal tubes.
Abstract 1366: Computer-modeled novel cancer targeting peptides for therapy and imaging
Authors: Sheng-Hung Wang, I-Ju Chen, Nai-Chuan Chang, Han-Chung Wu, Alice L. Yu, John Yu
Journal: Cancer Research (2011)

Abstract We have recently developed practical software programs for optimization of cancer targeting peptides, including combinatorial construction of 3D peptide library (Buildpep), binding pocket analyzer (PscanMS) and high accuracy protein-ligand scoring program (HotLig). Based on these programs, a strategy of structure-based optimization of cancer targeting peptides in silico is developed to target human GRP78 which consists of 654 amino acids. The homology modeling of human GRP78 was constructed through aligning amino acid sequence and 3D structure with its homologs. This protein contains two major structural domains, the peptide-binding domain and the ATPase. Based on the results from the molecular modeling, new peptide analogs were designed and examined for optimized binding to the targeted GRP78 through in silico analysis. We had thus delineated the pharmacophore description of binding motif targeting peptide-binding domain of GRP78 as Pro-X1-Leu-X2. Peptides possessing this motif can be applied in cancer-targeted drug delivery system. We have thus designed several new tumor-targeted peptides [P-12, P-13, and P-6]. Their ability to bind target protein was confirmed in subsequent in vitro binding through Biacore analysis. We next examined their capacity to target cancer cells in the in vitro binding with various cancer cells, and in vivo tumor imaging and targeted chemotherapeutic studies. The results indicate that these peptides exhibit promising therapeutic potential by their selective binding to cancer cells, but not normal cells. Notably, these peptide analogs can bind to breast cancer stem cell (CSC) population in xenografts of primary breast cancer suggesting that they can target breast CSC enriched subpopulation. The microSPECT/CT molecular imaging of a primary human breast tumors, BC0244, xenograft with 188Re-liposome-PEG-P12 or P13 peptide showed significantly more uptake of radioactivity as compared to 188Re- liposome-PEG-L-peptide in the BC0244 breast tumors in NOD/SCID mice at 6, 24 and 48 h after intravenous injection, and even greater difference was found as compared to that of 188Re-liposome alone. To further compare P12 labeled liposome with L-peptide labeled liposome for therapeutic efficacy, mice bearing BC0244 xenografts were distributed into 4 groups for treatment with P12-Lipo-Dox, L-peptide-Lipo-Dox, Lipo-Dox, and PBS. The tumor growth of P12-lipo-Dox group was 1.57-fold slower than that of the L-peptide group; both of them showed significant increase in the therapeutic efficiency than Lipo-Dox control. These optimized cancer targeting peptides may be useful for imaging and targeted therapy of cancers. 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 1366. doi:10.1158/1538-7445.AM2011-1366