tbuckley/cabot-search huggingface dataset:
Endotracheal Cuff Perforation Complicating Subclavian Venipuncture
Authors: W. Scott Klipper
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Percutaneous infraclavicular subclavian catheterization is a relatively benign and simple procedure. Nevertheless, the potential for complications is attested by their frequency (0.4% to 9.9%) and multiplicity. Borja's review enumerates 19 different complications.<sup>1</sup>Several authors<sup>2,3</sup>have been unable to show a relationship between the frequency of complications and the level of the training of the performer. Here is a previously undescribed complication of infraclavicular subclavian catheterization. <h3>Report of a Case.—</h3> A 46-year-old woman was hospitalized in shock following a motor vehicle accident in which she sustained multiple rib fractures, flail chest, hemopneumothorax, pulmonary contusions, and fracture of the left humerus. Four days later, the patient having progressive dyspnea, bilateral hemopneumothorax, opacification of the left lung, alveolar changes in the right lung, and deteriorating ventilation and oxygenation, a right chest tube was placed, and a nonfunctional left tube corrected. Both were now functional and placed on continuous
PERSPECTIVES ON THE PLACE OF ENVIRONMENTAL HEALTH AND PROTECTION IN PUBLIC HEALTH AND PUBLIC HEALTH AGENCIES
Authors: S. Kotchian
Journal: Annual Review of Public Health (1997)

▪ Abstract The field of environmental health and protection and the entire field of public health have repeatedly found themselves isolated from one another, unable to articulate the definition, mission, and goals of public health and the essential role for environmental health and protection in the provision of a healthy ecological and human environment. Environmental agencies often forget that they, too, are public health agencies; public health agencies that have had environmental health functions have divided and abdicated their environmental responsibilities, considering these to be “regulatory” rather than public health. This article reviews the history of environmental health and protection, its involvement within the field of public health, its eventual separation from other public health programs with resulting benefits and consequences, and what the future may hold for environmental health and protection activities as well as for the broader scope of public health of which these activities are a part.
Advances in Ultrasound Mediated Gene Therapy Using Microbubble Contrast Agents
Authors: Shashank R. Sirsi, Mark A. Borden
Journal: Theranostics (2012)

Microbubble ultrasound contrast agents have the potential to dramatically improve gene therapy treatments by enhancing the delivery of therapeutic DNA to malignant tissue.The physical response of microbubbles in an ultrasound field can mechanically perturb blood vessel walls and cell membranes, enhancing drug permeability into malignant tissue.In this review, we discuss literature that provided evidence of specific mechanisms that enhance in vivo gene delivery utilizing microbubble contrast agents, namely their ability to 1) improving cell membrane permeability, 2) modulate vascular permeability, and 3) enhance endocytotic uptake in cells.Additionally, we review novel microbubble vectors that are being developed in order to exploit these mechanisms and deliver higher gene payloads with greater target specificity.Finally, we discuss some future considerations that should be addressed in the development of next-generation microbubbles in order to improve in vivo microbubble gene delivery.Overall, microbubbles are rapidly gaining popularity as efficient gene carriers, and combined with their functionality as imaging contrast agents, they represent powerful theranostic tools for image guided gene therapy applications.
A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro
Authors: Melanie Adler, Susanne Ramm, Marc Hafner, Jeremy L. Muhlich, Esther Maria Gottwald, Elijah Weber, Alenka Jaklic, Amrendra Kumar Ajay, Daniel Svoboda, Scott Auerbach, Edward J. Kelly, Jonathan Himmelfarb, Vishal S. Vaidya
Journal: Journal of the American Society of Nephrology (2015)

Nephrotoxicity due to drugs and environmental chemicals accounts for significant patient mortality and morbidity, but there is no high throughput in vitro method for predictive nephrotoxicity assessment. We show that primary human proximal tubular epithelial cells (HPTECs) possess characteristics of differentiated epithelial cells rendering them desirable to use in such in vitro systems. To identify a reliable biomarker of nephrotoxicity, we conducted multiplexed gene expression profiling of HPTECs after exposure to six different concentrations of nine human nephrotoxicants. Only overexpression of the gene encoding heme oxygenase-1 (HO-1) significantly correlated with increasing dose for six of the compounds, and significant HO-1 protein deregulation was confirmed with each of the nine nephrotoxicants. Translatability of HO-1 increase across species and platforms was demonstrated by computationally mining two large rat toxicogenomic databases for kidney tubular toxicity and by observing a significant increase in HO-1 after toxicity using an ex vivo three-dimensional microphysiologic system (kidney-on-a-chip). The predictive potential of HO-1 was tested using an additional panel of 39 mechanistically distinct nephrotoxic compounds. Although HO-1 performed better (area under the curve receiver-operator characteristic curve [AUC-ROC]=0.89) than traditional endpoints of cell viability (AUC-ROC for ATP=0.78; AUC-ROC for cell count=0.88), the combination of HO-1 and cell count further improved the predictive ability (AUC-ROC=0.92). We also developed and optimized a homogenous time-resolved fluorescence assay to allow high throughput quantitative screening of nephrotoxic compounds using HO-1 as a sensitive biomarker. This cell-based approach may facilitate rapid assessment of potential nephrotoxic therapeutics and environmental chemicals.
CD8 T Cell Responses to Infectious Pathogens
Authors: Phillip Wong, Eric G. Pamer
Journal: Annual Review of Immunology (2003)

CD8 T cells respond to viral infections but also participate in defense against bacterial and protozoal infections. In the last few years, as new methods to accurately quantify and characterize pathogen-specific CD8 T cells have become available, our understanding of in vivo T cell responses has increased dramatically. Pathogen-specific T cells, once thought to be quite rare following infection, are now known to be present at very high frequencies, particularly in peripheral, nonlymphoid tissues. With the ability to visualize in vivo CD8 T cell responses has come the recognition that T cell expansion is programmed and, to a great extent, independent of antigen concentrations. Comparison of CD8 T cell responses to different pathogens also highlights the intricate relationship between microbially induced innate inflammatory responses and the kinetics, magnitude, and character of long-term T cell responses. This review describes recent progress in some of the major murine models of CD8 T cell-mediated immunity to viral, bacterial, and protozoal infection.
Early Pharmacokinetic and Pharmacodynamic Effects of Mixing Lispro With Glargine Insulin
Authors: Eda Cengiz, William V. Tamborlane, Melody Martin-Fredericksen, James Dziura, Stuart A. Weinzimer
Journal: Diabetes Care (2010)

OBJECTIVE Clinicians who treat children with type 1 diabetes often try to minimize the number of daily injections to reduce treatment burden and improve compliance. Despite the manufacturer's cautions against mixing glargine with rapid-acting insulin analogs, clinical studies have failed to demonstrate deleterious effects of mixing on glucose excursions or A1C levels. However, no formal glucose clamp studies have been performed to determine whether mixing with glargine has an adverse effect on the early pharmacodynamic action of rapid-acting insulin in humans. RESEARCH DESIGN AND METHODS To examine this question, euglycemic glucose clamps were performed twice, in random order, in 11 youth with type 1 diabetes (age 15.1 +/- 3 years, A1C 7.6 +/- 0.6%) with 0.2 units/kg lispro and 0.4 units/kg glargine, given either as separate or as a single mixed injection. RESULTS Mixing the two insulins shifted the time action curve to the right, with significantly lower glucose infusion rate (GIR) values after the mixed injections between 60 and 190 min and significantly higher values between 270 and 300 min, lowered the GIR(max) (separate 7.1 +/- 1 vs. mix 3.9 +/- 1, P = 0.03), and markedly delayed the time to reach GIR(max) (separate 116 +/- 8 min vs. mix 209 +/- 15 min, P = 0.004). The GIR area under the curve was significantly lower after the mixed injections. Mixing had similar effects on plasma insulin pharmacokinetics. CONCLUSIONS These data demonstrate that mixing lispro with glargine markedly flattens the early pharmacodynamic peak of lispro and causes a shift to the right in the GIR curve changes that might lead to difficulties in controlling meal-related glucose excursions.
Prevalence of Diabetes Complications in Adolescents With Type 2 Compared With Type 1 Diabetes
Authors: Maike C. Eppens, Maria E. Craig, Janine Cusumano, Stephen Hing, Albert K.F. Chan, Neville J. Howard, Martin Silink, Kim C. Donaghue
Journal: Diabetes Care (2006)

To compare the prevalence of diabetes complications and their risk factors in youth with type 1 versus type 2 diabetes.We performed a comparative clinic-based study of 1,433 patients with type 1 diabetes and 68 patients with type 2 diabetes aged <18 years from New South Wales, Australia. Retinopathy was assessed by seven-field stereoscopic retinal photography; albumin excretion rate from three consecutive, timed, overnight urine collections; peripheral neuropathy by thermal and vibration threshold; and autonomic neuropathy by pupillometry. HbA(1c) (A1C) and lipids were measured in all patients and C-peptide in patients with type 2 diabetes.In patients with type 1 versus type 2 diabetes, median (interquartile range) age was 15.7 years (13.9-17.0) and 15.3 years (13.6-16.4), respectively (P = 0.2), whereas median diabetes duration was 6.8 years (4.7-9.6) and 1.3 years (0.6-3.1), respectively (P < 0.0001). Retinopathy was significantly more common in patients with type 1 diabetes (20 vs. 4%, P = 0.04), while microalbuminuria and hypertension were significantly less common (6 and 16% in type 1 diabetes vs. 28 and 36% in type 2 diabetes). Rates of peripheral and autonomic neuropathy were similar (27 and 61% in type 1 diabetes vs. 21 and 57% in type 2 diabetes). In multivariate analyses, microalbuminuria was significantly associated with older age (odds ratio 1.3 [95% CI 1.2-1.5], P < 0.001) and systolic hypertension (3.63 [2.0-6.3], P < 0.001) in type 1 diabetes, while only higher A1C (1.7 [1.3-2.9], P = 0.002) was significant in patients with type 2 diabetes.Youth with type 2 diabetes have significantly higher rates of microalbuminuria and hypertension than their peers with type 1 diabetes, despite shorter diabetes duration and lower A1C. The results of this study support recommendations for early complications screening and aggressive targeting of glycemic control in patients with type 2 diabetes.
Senior doctors admit mistakes in campaign for more open culture
Authors: Rebecca Coombes
Journal: BMJ (2005)

More than a dozen senior British medical figures have publicly owned up to past clinical errors as part of a campaign to encourage other doctors to report incidents and improve the safety of patients.

The doctors have contributed their stories to a handbook for junior doctors, published last week by the National Patient Safety Agency.

The agency is calling on all doctors to report mistakes so that the root causes can be addressed. Research has shown that doctors are less likely than other health professionals to report when things go wrong because they do not have time or do not …
Vascular Effects of Apelin In Vivo in Man
Authors: Alan G. Japp, Nicholas L. Cruden, David A.B. Amer, Vivienne K.Y. Li, Ewan B. Goudie, Neil R. Johnston, Sushma Sharma, Ilene Neilson, David J. Webb, Ian L. Megson, Andrew D. Flapan, David E. Newby
Journal: Journal of the American College of Cardiology (2008)
GATA2 is required for lymphatic vessel valve development and maintenance
Authors: Jan Kazenwadel, Kelly L. Betterman, Chan-Eng Chong, Philippa H. Stokes, Young K. Lee, Genevieve A. Secker, Yan Agalarov, Cansaran Saygili Demir, David M. Lawrence, Drew L. Sutton, Sebastien P. Tabruyn, Naoyuki Miura, Marjo Salminen, Tatiana V. Petrova, Jacqueline M. Matthews, Christopher N. Hahn, Hamish S. Scott, Natasha L. Harvey
Journal: Journal of Clinical Investigation (2015)

Heterozygous germline mutations in the zinc finger transcription factor GATA2 have recently been shown to underlie a range of clinical phenotypes, including Emberger syndrome, a disorder characterized by lymphedema and predisposition to myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). Despite well-defined roles in hematopoiesis, the functions of GATA2 in the lymphatic vasculature and the mechanisms by which GATA2 mutations result in lymphedema have not been characterized. Here, we have provided a molecular explanation for lymphedema predisposition in a subset of patients with germline GATA2 mutations. Specifically, we demonstrated that Emberger-associated GATA2 missense mutations result in complete loss of GATA2 function, with respect to the capacity to regulate the transcription of genes that are important for lymphatic vessel valve development. We identified a putative enhancer element upstream of the key lymphatic transcriptional regulator PROX1 that is bound by GATA2, and the transcription factors FOXC2 and NFATC1. Emberger GATA2 missense mutants had a profoundly reduced capacity to bind this element. Conditional Gata2 deletion in mice revealed that GATA2 is required for both development and maintenance of lymphovenous and lymphatic vessel valves. Together, our data unveil essential roles for GATA2 in the lymphatic vasculature and explain why a select catalogue of human GATA2 mutations results in lymphedema.
Effect of Calcitriol on Prostate-Specific Antigen <i>In vitro</i> and in Humans
Authors: Tomasz M. Beer, Mark Garzotto, Byung Park, Motomi Mori, Anne Myrthue, Nicole Janeba, David Sauer, Kristine Eilers
Journal: Clinical Cancer Research (2006)

Abstract Background: Calcitriol, the natural ligand for the vitamin D receptor, has significant potential in prostate cancer treatment. Measurement of its antineoplastic activity in prostate cancer clinical trials may be complicated by effects of calcitriol on prostate-specific antigen (PSA) production. We examined the effects of calcitriol at similar concentration on cell proliferation, androgen receptor (AR) expression, and PSA production in vitro and on PSA concentrations in prostate cancer patients. Experimental Design: LNCaP prostate cancer cell proliferation was examined by cell counts 6 days after exposure to a range of concentrations of calcitriol. AR and PSA protein was quantified in LNCaP cells over 96 hours after exposure to 1 nmol/L calcitriol. Serum PSA and free PSA was serially measured by immunoassay over a period of 8 days in patients with hormone-naïve prostate cancer after a single dose of 0.5 μg/kg calcitriol. Results: Calcitriol treatment resulted in dose-dependent growth inhibition of LNCaP with ∼50% growth inhibition at the clinically achievable concentration of 1 nmol/L. Time-dependent up-regulation of AR expression and of PSA production in LNCaP cells was shown at the same concentration. No significant change in serum PSA or free PSA over 8 days was seen in eight subjects treated with a single dose of 0.5 μg/kg calcitriol. The analysis was powered to detect a 1.23-fold change between the baseline and day 8 serum PSA. Conclusions: At clinically achievable concentrations, calcitriol inhibits growth and induces AR and PSA expression in LNCaP cells. We did not detect similar changes in serum PSA or free PSA in patients exposed to similar concentrations of calcitriol. Thus, a PSA flare, predicted by preclinical systems, is unlikely to occur in patients and therefore unlikely to complicate interpretation of clinical trial outcomes.
Specific cutaneous involvement in the course of chronic myelomonocytic leukemia simultaneously with blastic leukemic transformation
Authors: Tomás Pozo-Román, F. Javier Menárguez-Palanca, Alfonso Gómez-Pineda, Carlos M. González-Herrada, Pablo Lázaro-Ochaita
Journal: Journal of the American Academy of Dermatology (1985)
H2-M3–Restricted T Cells in Bacterial Infection
Authors: Kristen M. Kerksiek, Dirk H. Busch, Ingrid M. Pilip, S. Elise Allen, Eric G. Pamer
Journal: The Journal of Experimental Medicine (1999)

Major histocompatibility complex (MHC) class Ib molecules have been implicated in CD8+ T cell–mediated defenses against intracellular bacterial infection, but the relative importance of MHC class Ib–restricted T cells in antimicrobial immunity is unknown. In this report, we use MHC tetramers to characterize T cell responses restricted by H2-M3, an MHC class Ib molecule that selectively presents N-formyl peptides. We find that sizeable H2-M3–restricted T cell responses, occurring earlier than MHC class Ia–restricted T cell responses, are mounted after primary infection with the intracellular bacterium Listeria monocytogenes. These H2-M3–restricted T cells are cytolytic and produce interferon γ. However, after a second L. monocytogenes infection, H2-M3–restricted memory T cell responses are minor in comparison to the much larger MHC class Ia–restricted responses. This first direct characterization of an MHC class Ib–restricted T cell response indicates that CD8+ T cells responding to L. monocytogenes infection can be divided into two groups: H2-M3–restricted responses, which provide rapid and quantitatively substantial effector function during primary infections but contribute relatively little to memory responses, and MHC class Ia–restricted responses, which expand later during primary infection but form memory T cells that respond rapidly and dramatically in response to subsequent infections by the same pathogen.
Do No Harm
Authors: Jack Coulehan
Journal: JAMA (2004)

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Atloido-Occipital Dislocation in a Small Child after Air-Bag Deployment
Authors: C A Angel, R A Ehlers
Journal: New England Journal of Medicine (2001)

Figure 1. A two-year-old girl riding in an automobile was involved in a low-speed collision in which the air bags deployed. At the time of the crash she was sitting unrestrained in the front passenger seat. She was apneic and unresponsive before the ambulance arrived. She was intubated at the scene, and resuscitation was instituted according to established guidelines. Except for numerous neck abrasions and burns, no other overt injuries were apparent on physical examination. A radiograph of the lateral cervical spine showed atloido-occipital dislocation (arrowheads), with a 4-cm gap between the occipital condyle and the superior articular facet of . . .
Editorial: ENDO Abstracts and Endocrine Reviews
Authors: R. Paul Robertson
Journal: Endocrine Reviews (2010)

I am delighted to announce that Endocrine Reviews has been selected as the permanent home for abstracts submitted to ENDO, the annual meeting of The Endocrine Society. The abstracts appear in an online supplement that accompanies this June issue, and the supplement will serve as a permanent archive. This is the first time that ENDO abstracts have been made available online in a permanent format. Researchers will now be able to access their abstracts through an easily found, easily navigated resource. Abstracts submitted to ENDO are a critical part of the Society’s annual meeting. They allow clinical and basic science researchers to disseminate their most current and exciting findings. The breadth and immediacy of research covered by these abstracts contributes to the diverse and stimulating atmosphere of the annual meeting. Preserving this is an important mission, and we at Endocrine Reviews are pleased to have helped initiate this new tradition. I hope you’ll join me in using this new resource and supporting its growth by contributing your abstracts to ENDO.
Enhanced renal prostaglandin production in the dog. I. Effects on renal function.
Authors: J Tannenbaum, J A Splawinski, J A Oates, A S Nies
Journal: Circulation Research (1975)

The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 and F2alpha.PGE2given at 0.01-0.3 mug/kg min--1 produced dose-related increases in urine flow, sodium and potassium excretion, free water clearance, and renal blood flow. The glomerular filtration rage increased only at the lowest dose and the calculated filtration fraction fell. Arachidonic acid at 1.0-30.0 mug/kg min--1 similarly produced dose-related increases in electrolyte excretion, but the increase in renal blood flow was much less than that produced by PGE2 and there were no changes in glomerular filtration rate, filtration fraction, or free water clearances. PGF2alpha had essentially no effects at infusion rates of 0.03-1.0 mug/kg min--1. All renal effects of arachidonic acid were inhibited by simultaneous infusions of an inhibitor of prostaglandin synthetase, 5, 8, 11,14-eicosatetraynoic acid (20:4). None of the effects produced by PGE2 were inhibited by 20:4. These results indicate that enhanced endogenous renal prostaglandin synthesis, which can be produced by arachidonate infusion, results in significant alterations of renal function. This finding strengthens the hypothesis that renal prostaglandins formed in vivo have physiological importance as regulators of renal function.