tbuckley/cabot-search huggingface dataset:
Treatment of von willebrand's disease and hypofibrinogenemia with single donor cryoprecipitate from plasma exchange donation
Authors: Bruce C. McLeod, Rajalaxmi McKenna, Richard J. Sassetti
Journal: American Journal of Hematology (1989)

Abstract Conventional replacement therapy for hypofibrinogenemia and von Willebrand's disease requires multiple donor exposures and a correspondingly high risk of blood‐borne infection. We describe the collection and successful use of cryoprecipitate derived from a single donor by plasma exchange donation to support such patients through major hemostatic stresses. The father of an epileptic patient with von Willebrand's disease produced cryoprecipitate containing 23,546 units of von Willebrand factor (vWF) in nine desmopressin‐stimulated donations; this provided total factor replacement for neurosurgery to remove a seizure focus. The average yield was 2,616 units per donation and the average VWF concentration in cryoprecipitate was 17.7 units/ml. The husband of a hypofibrinogenemic patient with a history of postpartum hemorrhage provided cryoprecipitate containing 13.4 g of fibrinogen in five donations; this supported his wife through parturition without recourse to other blood products. The average yield was 2.7 g per donation, and the average fibrinogen concentration was 15.3 g/liter. Plasma exchange donation is a practical alternative source for cryoprecipitate. It can provide vWF and fibrinogen that carry a reduced risk of infectious disease transmission.
When diagnosis is not enough
Authors: G. Jones
Journal: BMJ (2013)

Susceptibility to primary biliary cirrhosis (PBC) may be partly inherited although instances of PBC within families are only infrequently described. The records of 736 patients with PBC seen over a 25 year period were examined to identify those with a positive family history. Ten patients originating from eight families were identified, giving a frequency of 1.33%. They comprised mother and daughter pairs; in two families both mother and daughter had been seen at our clinic. The daughters presented at an earlier age, median 36 years (range 24-54), than the mothers, 52 years (50-81). During follow up one daughter (45 years) and six mothers have died (range 53-81 years) and two mothers and one daughter have had a transplant aged 57, 57, and 30 years respectively. It is concluded that familial PBC is not rare, that it is related to maternally inherited factors, and that disease tends to present earlier in the second generation.
Effect of the Dopamine D2 Receptor T Allele on Response Latency After Mild Traumatic Brain Injury
Authors: Thomas W. McAllister, C. Harker Rhodes, Laura A. Flashman, Brenna C. McDonald, Dorothy Belloni, Andrew J. Saykin
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The authors tested the hypothesis that the dopamine D2 receptor T allele (formerly described as the A1 allele) would be associated with poorer performance on memory and attention tasks following mild traumatic brain injury. METHOD: Thirty-nine patients with mild traumatic brain injury and 27 comparison subjects were genotyped. All subjects completed memory and attention tests, including the California Verbal Learning Test recognition task and the Continuous Performance Test. RESULTS: In both groups the T allele was associated with poorer performance on the California Verbal Learning Test recognition task. There was also a significant diagnosis-by-allele interaction on measures of response latency (Continuous Performance Test): the subjects with mild traumatic brain injury and the T allele had the worst performance. CONCLUSIONS: Genetic polymorphisms modulating central dopaminergic tone can affect cognitive outcome following mild traumatic brain injury.
Valproate-induced hepatic steatogenesis in rats
Authors: James H. Lewis, Hyman J. Zimmerman, Carlton T. Garrett, Elliot Rosenberg
Journal: Hepatology (1982)

The administration of high–dose valproic acid (VPA) (750 mg per kg) consistently produced significant microvesicular steatosis in mature Sprague–Dawley rats after 48 hr. Similar changes occurred in animals pretreated with phenobarbital which received a lower dose of VPA (350 mg per kg), but no steatosis was seen in animals treated with the low–dose VPA alone. The steatogenic effect of VPA is most likely mediated by a toxic metabolite. It can also be speculated that phenobarbital, by enhancing the inducing effects of the hepatic mixed–function oxidase system, may lead to increased conversion of VPA to a toxic metabolite. Young and weanling rats appeared to be resistant to the steatogenic effects of VPA. Reproduction of microvesicular steatosis in this experimental model may permit exploration of factors that enhance or inhibit VPA–induced hepatic injury.
Graduate Education in Primary Care
Authors: Robert S. Stern, Marion Jennings, Thomas L. Delbanco, Joseph L. Dorsey, John D. Stoeckle, Robert S. Lawrence
Journal: New England Journal of Medicine (1977)

To determine the financial requirements of an established primary-care educational program for house officers, we studied two prepaid and two fee-for-service Harvard Primary Care Program affiliated practices. Program-wide, each resident saw an average of 112 patients per month, with patient service costs of $2,580. With teaching and administrative expenses included, total monthly costs averaged $3,120 and $3,270 per trainee for prepaid and fee-for-service practices respectively. In fee-for-service practices, resident billings for patient services averaged $2,790, yielding revenues of $2,510 per month, which offset 77 per cent of total program costs. At current reimbursement rates, covering full program costs in the fee-for-service practices would require an increase of more than 40 per cent in resident-provided patient-care volume. By reducing time available for broad ambulatory experiences, such an increase would necessitate substantial program restructuring and limit opportunities for innovation in the Harvard Primary Care Program.
Low Circulating Vitamin B <sub>6</sub> Is Associated With Elevation of the Inflammation Marker C-Reactive Protein Independently of Plasma Homocysteine Levels
Authors: Simonetta Friso, Paul F. Jacques, Peter W.F. Wilson, Irwin H. Rosenberg, Jacob Selhub
Journal: Circulation (2001)

Background —Lower vitamin B 6 concentrations are reported to confer an increased and independent risk for cardiovascular disease (CVD). The mechanism underlying this relationship, however, remains to be defined. Other diseases, such as rheumatoid arthritis, are associated with reduced vitamin B 6 levels. Despite a clear distinction in pathophysiology, inflammatory reaction may be the major link between these diseases. We hypothesized a relationship between pyridoxal 5′-phosphate (PLP), the active form of vitamin B 6 , and the marker of inflammation C-reactive protein (CRP). We also evaluated whether total plasma homocysteine (tHcy), a well-defined risk factor for CVD and a major determinant of plasma PLP levels, had a possible role as a mediator of this hypothesized relationship. Methods and Results —Data from 891 participants from the population-based Framingham Heart Study cohort were analyzed. Subjects were divided into 2 groups according to normal or elevated CRP values: group 1, CRP &lt;6 mg/L; group 2, CRP ≥6 mg/L. Plasma PLP levels were substantially lower in group 2 than in group 1 (mean values in group 2, 36.5 nmol/L versus 55.8 nmol/L in group 1, P &lt;0.001). In a multiple logistic regression model adjusted for tHcy, the association of PLP with CRP remained highly significant ( P =0.003). Conclusions —Low plasma PLP is associated with higher CRP levels independently of tHcy. This observation may reflect a vitamin B 6 utilization in the presence of an underlying inflammatory process and represent a possible mechanism to explain the decreased vitamin B 6 levels in CVD.
Ultrastructural localization of histamine in human basophils and mast cells; changes associated with anaphylactic degranulation and recovery demonstrated with a diamine oxidase‐gold probe
Authors: Ann M. Dvorak
Journal: Allergy (1997)

Subcellular sites of histamine in purified human lung mast cells and human peripheral blood basophils were determined using a newly developed enzyme‐gold affinity method for ultrastructural analysis. The evolving morphologies of regulated secretion and recovery from regulated secretion in each cell showed that granule stores of histamine were released at early times after stimulation and re‐accumulated at later times post‐stimulus. Renewal of histamine granule stores occurred by multiple mechanisms including synthesis and conservation of granule materials and membranes.
The Idle Intravenous Catheter
Authors: Frank A. Lederle, Connie M. Parenti, Lisa C. Berskow, Kathleen J. Ellingson
Journal: Annals of Internal Medicine (1992)

▪ Objective: To assess the prevalence of idle peripheral intravenous (IV) catheters (those without any therapeutic use) on regular-care medical wards. ▪ Design: Observation, interviews, and chart review. ▪ Setting: A university-affiliated VA medical center. ▪ Patients: All 959 inpatients on 4 regular-care medical wards during a 6-week period, including 484IV catheter episodes and 2983 patient-days of IV catheter use. ▪ Main Outcome Measure: Idle IV catheter use. ▪ Results: Thirty-five percent of all IV catheter episodes (95% Cl, 32% to 38%) had 2 or more consecutive idle days. In only 6 of these (1%) could a specific reason for the catheter be determined. Seventeen percent of all patients on regular-care medical wards (Cl, 15% to 19%) had an idle IV catheter for 2 or more consecutive days. Twenty percent of all patient-days of IV catheter use were idle (Cl, 19% to 21%). ▪ Conclusions: Our data suggest that IV are frequently used unnecessarily. Future efforts to reduce IV catheter complication rates should focus on reducing unnecessary use as well as on improving techniques to reduce infection rates when use is appropriate.
CONCUSSION OF THE BRAIN.Read in the Section on Surgery and Anatomy at the Forty-fifth Annual Meeting of the American Medical Association, held at San Francisco, June 5-8, 1894.
Authors: L. C. LANE
Journal: JAMA (1894)

During the last forty years the subject of concussion or commotion, as the Germans and derivative Latin writers term it, has been a matter of careful study, observation and experimental research. It is caused by some external violence which communicates vibration, oscillation or minute movement to the anatomic elements of the parts acted upon. In the causation all observers agree; but what occurs in the constituent elements of the parts affected can not be said to be as yet satisfactorily settled. All the parts of the body may be the subject of such action: Bones, muscles, nerves, viscera; and some assert that the blood itself may be the subject of concussion. The study of the effects of concussion has been devoted chiefly to the brain; yet it seems certain that the same cause would be followed by like effects, no difference what part of the body might be the site;
Men of Conviction
Authors: John Lister
Journal: New England Journal of Medicine (1959)

CONVICTION and enthusiasm are perhaps two of the greatest attributes required of a successful practitioner of medicine. Conviction is akin to faith and is most apparent in those who truly practice medicine as a vocation; enthusiasm is a characteristic of youth, and it is a rare gift to be able to maintain its freshness throughout life.Perhaps the care of diabetic patients demands sustained enthusiasm and deep conviction on the part of the clinician even more than in other fields. Certainly, these must be two of the outstanding virtues of Dr. Joslin's character and of the long crusade he has . . .
Detrimental Effect of the Proteasome Inhibitor, Bortezomib in Bacterial Superantigen- and Lipopolysaccharide-induced Systemic Inflammation
Authors: Ashenafi Y Tilahun, Jayne E Theuer, Robin Patel, Chella S David, Govindarajan Rajagopalan
Journal: Molecular Therapy (2010)

Bacterial superantigen (BSAg)-induced toxic shock syndrome (TSS) and bacterial lipopolysaccharide (LPS)-induced shock are characterized by severe systemic inflammation. As nuclear factor kappaB (NF kappaB) plays an important role in inflammation and bortezomib, a proteasome inhibitor widely used in cancer chemotherapy, is a potent inhibitor of NF kappaB activation, we evaluated the therapeutic and prophylactic use of bortezomib in these conditions using murine models. Bortezomib prophylaxis significantly reduced serum levels of many cytokines and chemokines induced by BSAg. However, at 3 hours, serum level of TNF-a, an important cytokine implicated in TSS, was significantly reduced but not abolished. At 6 hours, there was no difference in the serum TNF-a levels between bortezomib treated and untreated mice challenged with staphylococcal enterotoxin B (SEB). Paradoxically, all mice treated with bortezomib either before or after BSAg challenge succumbed to TSS. Neither bortezomib nor BSAg was lethal if given alone. Serum biochemical parameters and histopathological findings suggested acute liver failure as the possible cause of mortality. Liver tissue from SEB-challenged mice treated with bortezomib showed a significant reduction in NF kappaB activation. Because NF kappaB-dependent antiapoptotic pathways protect hepatocytes from TNF-alpha-induced cell death, inhibition of NF kappaB brought forth by bortezomib in the face of elevated TNF-alpha levels caused by BSAg or LPS is detrimental.
Vitamin D and autoimmune thyroid diseases
Authors: Shaye Kivity, Nancy Agmon-Levin, Michael Zisappl, Yinon Shapira, Endre V Nagy, Katalin Dankó, Zoltan Szekanecz, Pnina Langevitz, Yehuda Shoenfeld
Journal: Cellular and Molecular Immunology (2011)
Malignant Glomus Tumor of the Thyroid Gland Where Is Heretofore an Unreported Organ: a Case Report and Literature Review
Authors: Dong Hae Chung, Na Rae Kim, Taeeun Kim, Jungsuk Ahn, Sangho Lee, Young Don Lee, Hyun Yee Cho
Journal: Endocrine Pathology (2014)
Control of Rheumatic Fever: How Are We Doing?
Authors: Edward A. Mortimer
Journal: JAMA (1977)

The American Heart Association has recently published updated recommendations for the prevention of acute rheumatic fever.<sup>1</sup>These recommendations are essentially the same as those first published 24 years ago<sup>2</sup>; the major differences are a consequence of the development of injectable penicillin G benzathine and of erythromycin, and the demonstration that group A streptococci frequently exhibit resistance to the tetracyclines. The similarities indicate that there have been very few changes in our approach to the control of rheumatic heart disease since it was first shown that acute rheumatic fever can be averted by appropriate treatment of the inciting streptococcal infection and that recurrent rheumatic fever can be prevented by continuous prophylaxis. We still do not know how to predict among those with streptococcal infections who are at risk for rheumatic fever, how to distinguish streptococcal carriers from those with actual infection except in retrospect, or exactly how the<i>Streptococcus</i>
ELECTRONEGATIVE LOW-DENSITY LIPOPROTEIN INCREASES ENDOTHELIAL EXPRESSION OF C-REACTIVE PROTEIN THROUGH LOX-1 RECEPTOR
Authors: Jonathan Xuhai Lu, Chih-Sheng Chu, Yu-Chen Wang, Jianwen Dong, Shu Hua Chen, Roger Huang, Chu-Huang Chen
Journal: Journal of the American College of Cardiology (2012)
HISTOLOGICAL CHANGES IN PSORIASIS TREATED WITH TOPICAL FLUOCINOLONE AND OCCLUSION.
Authors: A. W. McKENZIE
Journal: British Journal of Dermatology (1963)

Journal Article HISTOLOGICAL CHANGES IN PSORIASIS TREATED WITH TOPICAL FLUOCINOLONE AND OCCLUSION. Get access A. W. McKENZIE, M.B.(Edin.), M.R.C.P.(Lond.) A. W. McKENZIE, M.B.(Edin.), M.R.C.P.(Lond.) senior Registrar, St. John's Hospital for Diseases of the Skin, Lisle Street, London, W.C.2 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 75, Issue 11, 1 November 1963, Pages 434–440, https://doi.org/10.1111/j.1365-2133.1963.tb13539.x Published: 01 November 1963
Protection From Oxidized LDL–Induced Leukocyte Adhesion to Microvascular and Macrovascular Endothelium In Vivo by Vitamin C but Not by Vitamin E
Authors: Hans-Anton Lehr, Balz Frei, A. Maria Olofsson, Thomas E. Carew, Karl-E. Arfors
Journal: Circulation (1995)

Background The ability of oxidized LDL (oxLDL) to stimulate leukocyte–endothelium interaction is considered to be an important aspect of its proatherogenic action. Using intravital fluorescence microscopy in the dorsal skinfold chamber model in hamsters, we have previously shown that systemic administration of oxLDL stimulates leukocyte adhesion to microvascular endothelium through a mechanism that involves the generation and action of reactive oxygen species (ROS). Methods and Results Through the combined use of scanning electron microscopy and intravital microscopy in the same animal model, we demonstrate that oxLDL-induced leukocyte adhesion is not confined to the microcirculation but can also be observed on aortic endothelium. OxLDL-induced leukocyte adhesion to both microvascular and macrovascular endothelium was almost entirely prevented by pretreatment of the hamsters with dietary or intravenous vitamin C, which has the capacity to scavenge and neutralize ROS (arterioles: 20.5±16.4 cells/mm 2 [diet] and 16.3±23.8 cells/mm 2 [IV] versus 74.2±47.5 cells/mm 2 [control, P &lt;.01]; aorta: 1.0±0.4 cells/mm 2 [diet] and 1.1±0.5 cells/mm 2 [IV] versus 14.7±6.0 cells/mm 2 [control, P &lt;.01], 15 minutes after oxLDL, n=7 animals per group). Vitamin C pretreatment also completely prevented oxLDL-induced leukocyte-platelet aggregate formation in the bloodstream but did not affect leukocyte rolling along the microvascular endothelium. No inhibitory effect on any of the studied parameters was observed as a result of pretreatment of the animals with the lipid-soluble antioxidants vitamin E and probucol. Conclusions The protective effects of vitamin C on oxLDL-induced leukocyte adhesion and aggregate formation were seen at vitamin C plasma levels that can easily be reached in humans by diet or supplementation, suggesting that this could be one of the mechanisms by which vitamin C contributes to the well-documented protraction of atherogenesis as observed in large epidemiological surveys.
Protection by the gross saponins of Tribulus terrestris against cerebral ischemic injury in rats involves the NF-κB pathway
Authors: En-ping Jiang, Hong Li, Jian-guang Chen, Shi-jie Yang
Journal: Acta Pharmaceutica Sinica B (2011)

The aim of this study was to investigate whether the gross saponins of Tribulus terrestris (GSTT), a traditional Chinese herbal medicine, have neuroprotective effects on rats subjected to middle cerebral artery occlusion (MCAO), through nuclear factor-κB (NF-κB) pathway and inflammatory mediators. Cerebral ischemia was produced by MCAO in either untreated (control) or GSTT-pretreated rats, and the animals were examined for infarct volume, cerebral edema, neuro-behavioral abnormality and pathological changes. Meanwhile, the expression of NF-κB protein in brain tissue was analyzed on Western blots and the serum levels of TNF-α and IL-1 were determined by ELISA. The experimental results demonstrated that, compared with the control MCAO group, GSTT-pretreated MCAO group had significantly reduced infarct volume, brain edema and neuro-behavioral abnormality, and lesser degree of pathologic changes in the brain, as well as had lower levels of serum TNF-α and IL-1β, and higher levels of brain NF-κB (P<0.05). Furthermore, treatment with an NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) abolished the protective effects of GSTT against MCAO-induced cerebral ischemic injury. These results indicated that GSTT's ability to protect against cerebral ischemic injury was mediated through the NF-κB signaling pathway, and that GSTT may act through inhibition of the production of inflammatory mediators.
Reversal of acute and chronic synovial inflammation by anti-transforming growth factor beta.
Authors: S M Wahl, J B Allen, G L Costa, H L Wong, J R Dasch
Journal: The Journal of Experimental Medicine (1993)

Transforming growth factor beta (TGF-beta) induces leukocyte recruitment and activation, events central to an inflammatory response. In this study, we demonstrate that antagonism of TGF-beta with a neutralizing antibody not only blocks inflammatory cell accumulation, but also tissue pathology in an experimental model of chronic erosive polyarthritis. Intraarticular injection of monoclonal antibody 1D11.16, which inhibits both TGF-beta 1 and TGF-beta 2 bioactivity, into animals receiving an arthropathic dose of bacterial cell walls significantly inhibits arthritis. Inhibition was observed with a single injection of 50 micrograms antibody, and a 1-mg injection blocked acute inflammation > 75% compared with the contralateral joints injected with an irrelevant isotype control antibody (MOPC21) as quantitated by an articular index (AI = 0.93 +/- 0.23 for 1D11.16, and AI = 4.0 +/- 0 on day 4; p < 0.001). Moreover, suppression of the acute arthritis achieved with a single injection of antibody was sustained into the chronic, destructive phase of the disease (on day 18, AI = 0.93 +/- 0.07 vs. AI = 2.6 +/- 0.5; p < 0.01). The decreased inflammatory index associated with anti-TGF-beta treatment was consistent with histopathologic and radiologic evidence of a therapeutic response. These data implicate TGF-beta as a profound agonist not only in the early events responsible for synovial inflammation, but also in the chronicity of streptococcal cell wall fragment-induced inflammation culminating in destructive pathology. Interrupting the cycle of leukocyte recruitment and activation with TGF-beta antagonists may provide a mechanism for resolution of chronic destructive lesions.
Regulated Expression of a Tumor-Associated Antigen Reveals Multiple Levels of T-Cell Tolerance in a Mouse Model of Lung Cancer
Authors: Ann F. Cheung, Michel J.P. DuPage, H. Katie Dong, Jianzhu Chen, Tyler Jacks
Journal: Cancer Research (2008)

Abstract Maximizing the potential of cancer immunotherapy requires model systems that closely recapitulate human disease to study T-cell responses to tumor antigens and to test immunotherapeutic strategies. We have created a new system that is compatible with Cre-LoxP–regulatable mouse cancer models in which the SIY antigen is specifically overexpressed in tumors, mimicking clinically relevant TAAs. To show the utility of this system, we have characterized SIY-reactive T cells in the context of lung adenocarcinoma, revealing multiple levels of antigen-specific T-cell tolerance that serve to limit an effective antitumor response. Thymic deletion reduced the number of SIY-reactive T cells present in the animals. When potentially self-reactive T cells in the periphery were activated, they were efficiently eliminated. Inhibition of apoptosis resulted in more persistent self-reactive T cells, but these cells became anergic to antigen stimulation. Finally, in the presence of tumors overexpressing SIY, SIY-specific T cells required a higher level of costimulation to achieve functional activation. This system represents a valuable tool in which to explore sources contributing to T-cell tolerance of cancer and to test therapies aimed at overcoming this tolerance. [Cancer Res 2008;68(22):9459–68]