tbuckley/cabot-search huggingface dataset:
Management of infants with cerebral palsy
Authors: B. A. Stoll
Journal: BMJ (1969)

BlumsHepisodes, dyskinetic movement disorder, and adoption as a drug of abuse, may all be added to the record of a drug which has already been associated with a small number of fatalities.As with other drugs introduced as substitutes for the amphetamines, claims have been made that fenfluramine is a drug of low toxicity which does not stimulate the central nervous system.These assertions can no longer be sustained, and it is imperative that the same caution be exercised in the use of this drug as would be appropriate to other central nervous stimulants.-Iam, etc.,
OP12 * BORON NEUTRON CAPTURE THERAPY (BNCT): OPTIMISATION OF BORON UPTAKE AND PATIENT STRATIFICATION BY LAT1 IMPROVES BIOLOGICAL TARGETING WITH REDUCED RADIATION TIME, AND INCREASED CHANCE OF TUMOUR CONTROL
Authors: G. Cruickshank, A. Detta, D. Ngoga, N. Lockyer, B. Pheonix, Z. Ghani, S. Green
Journal: Neuro-Oncology (2014)

INTRODUCTION: The interaction between an epithermal neutron beam, now deliverable with LINAC technology, and tumour cell accumulated Boron from borono-phenylalanine (BPA), releases an intracellular alpha particle and Li ion causing irrecoverable double strand DNA breaks, insensitive to hypoxia and cell cycle state. Augmented uptake of BPA in GBM cells due to LAT1 upregulation allows targeting of tumour cells, but optimisation of BPA delivery, and neutron exposure time, need clarification before a Phase I trial. METHOD: A pharmacokinetic (Pk)study of newly formulated BPA delivered by iv or close arterial infusion with preinfusion barrier opening, has been carried out in 10 new GBM patients. Plasma, ECF microdialysis, LAT1 activity, Tumour and brain around tumour (BAT) boron10 concentrations of have been used to model the optimum period for neutron beam therapy. RESULTS: 75% of GBM cells are LAT 1 positive, many more than the proliferative index PCNA. Pk studies indicate a three compartment model of BPA cell uptake rate limited by LAT1 exchange kinetics plateauing at four hours. LAT 1 density determines cell Boron dose. LAT1 uptake activity varies between core tumour cells and BAT tumour cells. LAT1 expression maybe particularly elevated in patients with unmethylated MGMT promoter. CONCLUSION: Patients with >50% LAT1 expression are likely to benefit from BNCT with non-LAT1 cells best treated with reduced fraction RT. The BPA uptake pattern favours BAT region tumour cells: those left after surgery regardless of -oxic or cell cycle status. BNCT offers a way of RT dose escalation to discontiguous GBM cells avoiding normal brain, exploits the biology of LAT1 and may offer benefit to patients unresponsive to Temozolomide.
Lymphocyte Subsets in Primary Biliary Cirrhosis
Authors: Kenneth B. Miller, Grace H. Elta, Richard A. Rudders, Marshall M. Kaplan
Journal: Annals of Internal Medicine (1984)

To ascertain whether abnormalities of circulating T-cell subsets are a cause or effect of primary biliary cirrhosis, we analyzed peripheral blood lymphocytes from 44 patients at various stages of disease. The percentages of total T cells and helper/inducer cells were normal in early disease whereas the percentage of suppressor/inducer cells was increased. The percentage of all T-cell subsets fell steadily as the disease progressed histologically. The percentages in late (cirrhotic) disease were the same as those in patients with other types of cirrhosis. We conclude that most of the previously reported abnormalities of circulating T cells are secondary to the histologic progression of primary biliary cirrhosis.
Two Methods for Improved Venous Access in Acute Leukemia Patients
Authors: James C. Wade
Journal: JAMA (1981)

Arteriovenous fistulae and long-term indwelling right atrial (Hickman) catheters have been used as methods to improve venous access in patients with acute leukemia. The creation of 28 fistulae provided short duration of function (median, 12 days), with eight fistulae functioning less than 24 hours. Complications were negligible, and no increase in the incidence of bacteremia occurred. Fifty-one Hickman catheters have been placed, with a median placement granulocyte count of 335/microliters. The median duration of function has been 91 days or more, with 19 still functioning and 25 other catheters functioning at the time of the patient's death. Complications have been minimal, with substantial postoperative hemorrhage occurring primarily in patients with active disseminated intravascular coagulopathy at the time of catheter placement. Catheter-associated infections were uncommon. The overall incidence of bacteremia was not increased in patients with Hickman catheters, and 28 of the 30 bacteremias that occurred while catheters were in place (three catheter associated) resolved without catheter removal. The Hickman catheter is a safe, reliable device for improvement of venous access in adult patients with acute leukemia.
Serial Biomarker Measurements in Ambulatory Patients With Chronic Heart Failure
Authors: Wayne L. Miller, Karen A. Hartman, Mary F. Burritt, Diane E. Grill, Richard J. Rodeheffer, John C. Burnett, Allan S. Jaffe
Journal: Circulation (2007)

Background— Cardiac troponin T (cTnT) and B-type natriuretic peptide (BNP) have been used to estimate prognosis in heart failure; however, most studies have evaluated decompensated patients with single measurements. To determine if there are advantages to serial measurements, we evaluated stable chronic heart failure patients every 3 months for 2 years. Methods and Results— A cohort of 190 New York Heart Association class III–IV heart failure patients was prospectively enrolled from June 2001 to January 2004. Primary end points were death, cardiac transplantation, or hospitalization. At study enrollment cTnT was &lt;0.01 ng/mL in 87 (45.8%) patients, 0.01 to 0.03 ng/mL in 50 (26.3%) patients, and &gt;0.03 ng/mL in 53 (27.9%) patients. An increase in cTnT above normal (&lt;0.01 ng/mL) carried a 3.4-fold increased risk ( P =0.019). Further increases (≥20%) from an elevated level worsened the overall risk (hazard ratio, 5.09; P &lt;0.001). BNP was elevated (&gt;95th percentile for age and gender normal population) in 122 (64.2%) patients. An elevation of BNP from normal at any time during the study was associated with a poor outcome, but, once elevated, further changes in BNP (increases or decreases) remained associated with the same risk (hazard ratio, 5.09; P &lt;0.001). Combined elevations of cTnT (&gt;0.03 ng/mL) and BNP defined the highest risk group (hazard ratio, 8.58; P &lt;0.001). Conclusions— Elevations of cTnT or BNP from normal detected at any time during clinical follow-up in ambulatory patients with chronic heart failure are highly associated with an increased risk of events. Further increases in cTnT contribute to additional risk. Combined elevations of cTnT and BNP contribute the highest risk. The ability to monitor changes by serial measurements adds substantially to the assessment of risk in this patient population.
Opiate antagonists and thyrotropin-releasing hormone. II. Potential role in the treatment of central nervous system injury
Authors: A. I. Faden
Journal: JAMA (1984)

PARALYSIS resulting from CNS injury has been recognized for more than 2,000 years. Although much has been learned about the pathophysiology of spinal cord injury, head injury, and stroke, therapeutic management of such patients, particularly with regard to pharmacologic interventions, has progressed relatively little. This lack of progress has generated a sense of futility among physicians who treat these conditions. Yet a number of novel therapeutic measures have been suggested over the past few years, based on the successful alteration of neurological outcome following experimental CNS injury. Of particular interest have been the observations that opiate antagonists may improve neurological recovery in experimental stroke, head injury, and spinal cord injury and that thyrotropin-releasing hormone (TRH) may significantly enhance motor recovery after traumatic spinal cord injury. <h3>CNS Injury—Pathophysiological Considerations</h3> During the past decade it has become increasingly clear that traumatic or ischemic insults to the CNS may cause neurological deficits through
Microscopic polyangiitis mimicking Henoch-Schönlein purpura followed by severe renal involvement: a diagnostic role for antineutrophil cytoplasmic autoantibody
Authors: S. Akimoto, O. Ishikawa, Y. Tsukada, S. Yano, Y. Miyachi
Journal: British Journal of Dermatology (1997)

Journal Article Microscopic polyangiitis mimicking Henoch–Schönlein purpura followed by severe renal involvement: a diagnostic role for antineutrophil cytoplasmic autoantibody Get access S. Akimoto, S. Akimoto Department of Dermatology, Gunma University School of Medicinne, 3–39–22 Showa–machi Maebashi, Gunma 371, Japan Search for other works by this author on: Oxford Academic Google Scholar O. Ishikawa, O. Ishikawa Department of Dermatology, Gunma University School of Medicinne, 3–39–22 Showa–machi Maebashi, Gunma 371, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Tsukada, Y. Tsukada Department of Third Internal Medicine, Gunma University School of Medicine, 3–39–22 Showa–machi Maebashi, Gunma 371, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Yano, S. Yano Department of Third Internal Medicine, Gunma University School of Medicine, 3–39–22 Showa–machi Maebashi, Gunma 371, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Miyachi Y. Miyachi Department of Dermatology, Gunma University School of Medicinne, 3–39–22 Showa–machi Maebashi, Gunma 371, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 136, Issue 2, 1 February 1997, Pages 298–299, https://doi.org/10.1111/j.1365-2133.1997.tb14930.x Published: 01 February 1997
Mast Cells Can Mediate Vascular Permeability through Regulation of the PI3K–HIF-1α–VEGF Axis
Authors: Kyung Sun Lee, So Ri Kim, Seoung Ju Park, Kyung Hoon Min, Ka Young Lee, Yeong Hun Choe, Seung Yong Park, Ok Hee Chai, Xin Zhang, Chang Ho Song, Yong Chul Lee
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Bronchial inflammation is usually accompanied by increased vascular permeability. Mast cells release a number of mediators that act directly on the vasculature, resulting in vasodilatation, increased permeability, and subsequent plasma protein extravasation. Vascular endothelial growth factor (VEGF) has been implicated to contribute to asthmatic tissue edema through its effect on vascular permeability. However, the effects of mast cells on VEGF-mediated signaling in allergic airway disease are not clearly understood.An aim of the present study was to investigate the role of mast cells on VEGF-mediated signal transduction in allergic airway disease.We used genetically mast cell-deficient WBB6F(1)-Kit(W)/Kit(W-v) (W/W(v)) mice and the congenic normal WBB6F(1)(+/+) mouse model for allergic airway disease to investigate the role of mast cells on VEGF-mediated signal transduction in allergic airway disease, more specifically in vascular permeability.Our present study, with ovalbumin (OVA)-sensitized without adjuvant and OVA-challenged mice, revealed the following typical pathophysiologic features of allergic airway diseases: increased inflammatory cells of the airways, airway hyperresponsiveness, increased vascular permeability, and increased levels of VEGF. However, levels of VEGF and plasma exudation in W/W(v) mice after OVA inhalation were significantly lower than levels in WBB6F(1)(+/+) mice. Moreover, mast cell-reconstituted W/W(v) mice restored vascular permeability and VEGF levels similar to those of the WBB6F(1)(+/+) mice. Our data also showed that VEGF expression was regulated by hypoxia-inducible factor-1alpha (HIF-1alpha) activation through the phosphatidylinositol 3-kinase (PI3K)-HIF-1alpha pathway in allergic airway disease.These results suggest that mast cells modulate vascular permeability by the regulation of the PI3K-HIF-1alpha-VEGF axis.
Review: Cholinesterase inhibitors do not prevent dementia in patients with mild cognitive impairment
Authors: Calvin Hirsch
Journal: Annals of Internal Medicine (2014)

ACP Journal Club15 April 2014Review: Cholinesterase inhibitors do not prevent dementia in patients with mild cognitive impairmentCalvin Hirsch, MDCalvin Hirsch, MDUniversity of California, Davis Medical Center, Sacramento, California, USA (C.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-160-8-201404150-02011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationCooper C, Li R, Lyketsos C, Livingston G. Treatment for mild cognitive impairment: systematic review. Br J Psychiatry. 2013;203:255-64. https://pubmed.ncbi.nlm.nih.gov/24085737Clinical Impact RatingsGIM/FP/GP: Geriatrics: Neurology: References1 Doody RS, Ferris SH, Salloway S, et al. Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial. Neurology. 2009;72:1555-61. [PMID: 19176895] Google Scholar2 Russ TC, Morling JR. Cholinesterase inhibitors for mild cognitive impairment. Cochrane Database Syst Rev. 2012;9:CD009132. [PMID: 22972133] Google Scholar3 Buschert VC, Friese U, Teipel SJ, et al. Effects of a newly developed cognitive intervention in amnestic mild cognitive impairment and mild Alzheimer's disease: a pilot study. J Alzheimers Dis. 2011;25:679-94. [PMID: 21483095] Google Scholar4 Winblad B, Wimo A, Engedal K, et al. 3-year study of donepezil therapy in Alzheimer's disease: effects of early and continuous therapy. Dement Geriatr Cogn Disord. 2006;21:353-63. [PMID: 16508298] Google Scholar Author, Article, and Disclosure InformationAuthors: Calvin Hirsch, MDAffiliations: University of California, Davis Medical Center, Sacramento, California, USA (C.H.)This article was published at Annals.org on 1 April 2014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited by“Personal Training” 15 April 2014Volume 160, Issue 8Page: JC11KeywordsAlzheimer diseaseCholinesterase inhibitorsCognitionDementiaMild cognitive impairmentPolyunsaturated fatty acidSystematic reviewsVitamin EVitamins ePublished: 15 April 2014 Issue Published: 15 April 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Phorbol myristate acetate stimulates ATP-dependent calcium transport by the plasma membrane of neutrophils.
Authors: H Lagast, T Pozzan, F A Waldvogel, P D Lew
Journal: Journal of Clinical Investigation (1984)

We studied the effect of phorbol myristate acetate (PMA) on the plasma membrane ATP-dependent calcium pump in neutrophils. Plasma membrane-enriched fractions ("podosomes") from PMA-stimulated guinea pig neutrophils exhibited a twofold stimulation of ATP-dependent calcium transport when compared with control podosomes. The stimulatory effect was rapid (beginning less than 2 min after exposure to PMA) and reached maximal values within 5 min. PMA increased the maximum velocity but not the affinity of the calcium pump for Ca++. Pump activation was not preceded by a rise in cytosolic free calcium concentration [Ca++]i, as assessed by the intracellularly trapped fluorescent calcium indicator Quin 2, but instead slightly lowered [Ca++]i and prevented the rise in [Ca++]i normally induced by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine. These results suggest that the calcium pump in the plasma membrane of neutrophils may be stimulated by calcium-independent pathways, and that this activation could be one of the earliest events mediating some of the effects of phorbol esters.
Cyclophosphamide Enhances the Antitumor Efficacy of Adoptively Transferred Immune Cells through the Induction of Cytokine Expression, B-Cell and T-Cell Homeostatic Proliferation, and Specific Tumor Infiltration
Authors: Laura Bracci, Federica Moschella, Paola Sestili, Valentina La Sorsa, Mara Valentini, Irene Canini, Sara Baccarini, Sonia Maccari, Carlo Ramoni, Filippo Belardelli, Enrico Proietti
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Immunotherapy is a promising antitumor strategy, which can be successfully combined with current anticancer treatments, as suggested by recent studies showing the paradoxical chemotherapy-induced enhancement of the immune response. The purpose of the present work is to dissect the biological events induced by chemotherapy that cooperate with immunotherapy in the success of the combined treatment against cancer. In particular, we focused on the following: (a) cyclophosphamide-induced modulation of several cytokines, (b) homeostatic proliferation of adoptively transferred lymphocytes, and (c) homing of transferred lymphocytes to secondary lymphoid organs and tumor mass. Experimental Design: Here, we used the adoptive transfer of tumor-immune cells after cyclophosphamide treatment of tumor-bearing mice as a model to elucidate the mechanisms by which cyclophosphamide can render the immune lymphocytes competent to induce tumor rejection. Results: The transfer of antitumor immunity was found to be dependent on CD4+ T cells and on the cooperation of adoptively transferred cells with the host immune system. Of note, tumor-immune lymphocytes migrated specifically to the tumor only in mice pretreated with cyclophosphamide. Cyclophosphamide treatment also promoted homeostatic proliferation/activation of transferred B and T lymphocytes. Optimal therapeutic responses to the transfer of immune cells were associated with the cyclophosphamide-mediated induction of a “cytokine storm” [including granulocyte macrophage colony-stimulating factor, interleukin (IL)-1β, IL-7, IL-15, IL-2, IL-21, and IFN-γ], occurring during the “rebound phase” after drug-induced lymphodepletion. Conclusions: The ensemble of these data provides a new rationale for combining immunotherapy and chemotherapy to induce an effective antitumor response in cancer patients.
FURTHER STUDIES ON PASSIVE TRANSFER OF TOLERANCE TO PYROGENICITY OF BACTERIAL ENDOTOXIN
Authors: Henry H. Freedman
Journal: The Journal of Experimental Medicine (1960)

The effect of various schedules for inducing tolerance to bacterial endotoxin in donor rabbits upon suitability for demonstration of passive transfer of tolerance to pyrogenicity in normal recipients has been investigated. Long-term treatment of donors, through 5 weeks, is no more effective than a brief series of injections, adding further evidence that tolerance is not attributable to specific antibody to the endotoxin. Qualitative differentiation of the febrile pattern of passively tolerant recipients from that seen in control animals depends upon the magnitude of the test dose of pyrogen. Passively tolerant rabbits respond to endotoxin with an acute leucopenia equivalent to that seen in controls suffering a full biphasic fever. Animals given daily injections of endotoxin continue to show the acute leucopenia, despite the early modification of the course of fever characteristic of endotoxin tolerance. The assumption that the leucopenia reflects damage to the leucocytes, with release of endogenous pyrogen, is not consistent with these findings. Rabbits rendered leucopenic by nitrogen mustard and then given endotoxin exhibit a rapidly developing fever of greater than normal intensity, the exaggeration of the febrile response being proportional to the severity of the induced leucopenia. The implications of these findings for the pathogenesis of endotoxin-induced fever are discussed. The evidence supports the hypothesis that endotoxin produces fever by direct action rather than by release of endogenous leucocytic pyrogen. It is postulated that the lesser fever, in animals having normal numbers of circulating leucocytes, reflects a limitation of available endotoxin by the known rapid sequestration in the white blood cells at the time of the acute leucopenia. It is further suggested that the biphasic febrile response of the normal rabbit results from reinoculation of the blood stream by the temporarily sequestered endotoxin, the RES of the tolerant animal clearing the released endotoxin at a rate sufficient to prevent triggering the second phase of fever.
Managing the Demand for Global Health Education
Authors: Vanessa B. Kerry, Thumbi Ndung'u, Rochelle P. Walensky, Patrick T. Lee, V. Frederick I. B. Kayanja, David R. Bangsberg
Journal: PLoS Medicine (2011)

Vanessa Kerry and colleagues discuss how to manage the unprecedented growth in and demand for global health programs in the United States, Europe and other high-income countries.
UN and aid groups intensify efforts to contain cholera outbreak in Haiti
Authors: J. Zarocostas
Journal: BMJ (2010)

United Nations agencies and aid groups have intensified their efforts to contain the cholera outbreak in Haiti but fear their efforts could be jeopardised by Hurricane Tomas, which is expected to reach the island on 5 November.

The UN Office for the Coordination of Humanitarian Affairs said contingency plans have been activated, including the replenishment of health inventories …
Prophylactic Human Semen Cryobanking
Authors: Jerome Alan Silbert
Journal: JAMA (1972)

To the Editor.—  The use of human semen for donor insemination has been found to be safe and efficacious. 1 When the frozen semen is stored at the temperature of liquid nitrogen, all biological activity ceases and the semen may be preserved for long periods of time. Frozen human semen has, in fact, been used successfully after ten years of storage. 2   When young men who may yet wish to have children are to undergo procedures that may decrease their fertility, prophylactic cryobanking of semen warrants serious consideration. Younger men referred for prostatic surgery, bladder neck surgery, or for radiotherapy or chemotherapy, particularly of those malignant neoplasms that have a high probability of cure (eg, seminoma, Hodgkin's disease) may find it an advantage to deposit an adequate supply for procreational use at a later date before the consequences of the treatment significantly diminish the quality of the semen.  Human semen
Cardioplegia versus intermittent ischaemic arrest in coronary bypass surgery.
Authors: J R Pepper, E Lockey, S Cankovic-Darracott, M V Braimbridge
Journal: Thorax (1982)

No definitive method of myocardial preservation has been established and conclusions based on experimental data may not be applicable to patients with coronary artery disease. Fifty patients undergoing coronary bypass grafting were randomly assigned to one of two groups for myocardial preservation. In group A cold cardioplegia with external cardiac cooling was used and in group B ischaemic arrest with mild systemic cooling to 32 degrees C. Myocardial preservation was assessed by analysis of enzymes specific to the heart, left ventricular biopsy, and electrocardiography. Equal protection of the myocardium was provided in both groups but the mean cross-clamp time in group A was significantly longer than in group B. This implies that cardioplegia confers greater protection than intermittent ischaemic arrest.
Mutations associated with neutropenia in dogs and humans disrupt intracellular transport of neutrophil elastase
Authors: Kathleen F Benson, Feng-Qian Li, Richard E Person, Dalila Albani, Zhijun Duan, Jeremy Wechsler, Kimberly Meade-White, Kayleen Williams, Gregory M Acland, Glenn Niemeyer, Clinton D Lothrop, Marshall Horwitz
Journal: Nature Genetics (2003)