tbuckley/cabot-search huggingface dataset:
Unmasking Disease-Specific Cerebral Blood Flow Abnormalities: Mood Challenge in Patients With Remitted Unipolar Depression
Authors: Mario Liotti, Helen S. Mayberg, Scott McGinnis, Stephen L. Brannan, Paul Jerabek
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Remitted major depressive disorder is a vulnerable clinical state, suggesting persistence of an underlying disease diathesis between episodes. To investigate neural correlates of such risk and to identify potential depression trait markers, euthymic unipolar patients in remission, acutely depressed patients, and never-depressed volunteers were studied before and after transient sad mood challenge. METHOD: Common and differential changes in regional blood flow among the groups relative to the baseline state were examined with [15O]H2O positron emission tomography after provocation of sadness with autobiographical memory scripts. RESULTS: Mood provocation in both depressed groups resulted in regional cerebral blood flow (rCBF) decreases in medial orbitofrontal cortex Brodmann's area 10/11, which were absent in the healthy group. In the remitted group, mood provocation produced a unique rCBF decrease in pregenual anterior cingulate 24a. The main effects in healthy subjects, an rCBF increase in subgenual cingulate Brodmann's area 25 and a decrease in right prefrontal cortex Brodmann's area 9, were not present in the depressed groups. CONCLUSIONS: Mood challenge in unipolar euthymic patients in full remission unmasks an apparent depression trait marker. The pattern of acute CBF changes is distinct from that seen in euthymic healthy volunteers and mirrors the untreated depressed state seen during a major depressive episode and the pattern of change seen in depressed patients. These findings suggest that disease-specific modifications of pathways mediating transient mood changes are present in unipolar depression independent of clinical illness status. These findings have implications for understanding the vulnerability of remitted patients for illness relapse.
MECHANISM OF EXACERBATION OF RHEUMATOID SYNOVITIS BY TOTAL-DOSE IRON-DEXTRAN INFUSION: IN-VIVO DEMONSTRATION OF IRON-PROMOTED OXIDANT STRESS
Authors: P.G. Winyard, S. Chirico, D.R. Blake, J.M.C. Gutteridge, J. Lunec
Journal: The Lancet (1987)
Specific anti-influenza virus antibody production in vitro by lymphocytes from a subset of patients with hypogammaglobulinemia.
Authors: R Yarchoan, H S Schneider, B B Wray, D L Nelson
Journal: Journal of Clinical Investigation (1983)

Specific anti-influenza virus antibody production in vitro was studied in peripheral blood mononuclear cells from 17 patients with hypogammaglobulinemia. Cells obtained from 6 of 12 patients with common variable hypogammaglobulinemia produced anti-influenza virus antibody, predominantly of the IgM isotype, when cultured in vitro with type A influenza virus. No antibody was produced in vitro, however, by cells from either of two patients with Bruton's type X-linked hypogammaglobulinemia or by cells from any of three patients with X-linked hypogammaglobulinemia and isolated growth hormone deficiency. These studies demonstrate that peripheral blood mononuclear cells from a subset of patients with common variable hypogammaglobulinemia retain the potential to produce specific antibody in response to antigenic stimulation.
Use of miRNA Response Sequences to Block Off-target Replication and Increase the Safety of an Unattenuated, Glioblastoma-targeted Oncolytic HSV
Authors: Lucia Mazzacurati, Marco Marzulli, Bonnie Reinhart, Yoshitaka Miyagawa, Hiroaki Uchida, William F Goins, Aofei Li, Balveen Kaur, Michael Caligiuri, Timothy Cripe, Nino Chiocca, Nduka Amankulor, Justus B Cohen, Joseph C Glorioso, Paola Grandi
Journal: Molecular Therapy (2014)

Glioblastoma multiforme (GBM) is an aggressive brain cancer for which there is no effective treatment. Oncolytic HSV vectors (oHSVs) are attenuated lytic viruses that have shown promise in the treatment of human GBM models in animals, but their efficacy in early phase patient trials has been limited. Instead of attenuating the virus with mutations in virulence genes, we engineered four copies of the recognition sequence for miR-124 into the 3'UTR of the essential ICP4 gene to protect healthy tissue against lytic virus replication; miR-124 is expressed in neurons but not in glioblastoma cells. Following intracranial inoculation into nude mice, the miR-124-sensitive vector failed to replicate or show overt signs of pathogenesis. To address the concern that this safety feature may reduce oncolytic activity, we inserted the miR-124 response elements into an unattenuated, human receptor (EGFR/EGFRvIII)-specific HSV vector. We found that miR-124 sensitivity did not cause a loss of treatment efficiency in an orthotopic model of primary human GBM in nude mice. These results demonstrate that engineered miR-124 responsiveness can eliminate off-target replication by unattenuated oHSV without compromising oncolytic activity, thereby providing increased safety.
Mepolizumab May Substantially Reduce Asthma Exacerbations
Authors: Anita Slomski
Journal: JAMA (2014)

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Saigon Medical School: An Experiment in International Medical Education (An Account of the American Medical Association's Medical Education Project in South Viet Nam, 1966-1975)
Authors: E. Grey Dimond
Journal: JAMA (1989)

It is remarkable how quickly a current event becomes history. Even more remarkable is how certain events, when their history is read, seem nearly inexplicable. How did the events of the time make logical the actions? This book is a serious, almost day-by-day explication of how the American Medical Association and substantial university medical centers got involved in seeking to create an American medical school and hospital satellite in Saigon, Vietnam. This report is by three of those who were deeply involved. All three of the authors gave years of their prime time and effort to the Americanization of the Saigon Medical School, and my remarks, written more than a decade after the departure of the United States from Vietnam, have the obvious flaw of carping from the safety of today, without the pressures of patriotism, the desire to demonstrate commitment, or the excitement that swept up these medical educators
Abstract 3138: The Independent Prognostic Value Of Contractile And Coronary Flow Reserve In Dilated Cardiomyopathy: A Dipyridamole Stress Echo Study
Authors: Fausto Rigo, Sonia Gherardi, Maurizio Galderisi, Lorenza Pratali, Lauro Cortigiani, Rosa Sicari, Eugenio Picano
Journal: Circulation (2006)

Objective: The aim of the study was to evaluate the prognostic value of Doppler echocardiographic derived CFR over inotropic response in patients with DCM. Methods: We evaluated 132 DCM patients (9...
Rapid release of Ole e 1 from Olive pollen using different solvents
Authors: J. Carnés, E. Fernández‐Caldas, L. Boluda, M. Casanovas, J. Sastre, M. Lluch Bernal, M. Blanca
Journal: Allergy (2002)

Solubility is an important characteristic of allergenic molecules. The aim of this study was to investigate the solubility of Ole e 1, a major allergen of Olea europaea, using different solvents.Olea europaea pollen was placed in a glass column and extracted using three different solvents: deionized water, phosphate buffer 0.01 M (PBS) and normal saline (NaCl 0.9%). Several fractions were collected after extraction with each solvent and pooled based on individual protein content. Each fraction corresponded to a different elution profile, as determined by linear regression analysis. After 130 min of extraction, the pollen that remained in the column was further extracted overnight. A control olive pollen extract was also prepared with each solvent. The antigenic and allergenic profiles of all the eluted and pooled fractions were analysed by SDS-PAGE and inmmunoblots. Protein and Ole e 1 content and the amount of protein needed to produce 50% inhibition were also calculated. Ten patients were skin prick tested with the fractions obtained with deionized water.Four elution profiles were obtained using deionized water as the extracting solution and three with the two other solvents. The three solvents produced different kinetics of allergen release. Ole e 1 was rapidly released when water was used, obtaining a total of 256 micro g of Ole e 1/ml after only 7 min of extraction (fraction EC1). Using PBS, or NaCl 0.9%, the release of Ole e 1 started after 4 and 9 min of extraction, respectively. The highest amount ofOle e 1 was eluted after 44 and 26 min, with a total concentration of 162 and 203 micro g of Ole e 1/ml, respectively. The presence of Ole e 1 in each phase was verified by SDS-PAGE and immunoblot analyses.The extracting solution seems to determine the antigenic profile of olive pollen extracts. Ole e 1 is rapidly released from the pollen grain after extraction in deionized water. The solubility seems to be affected by the use of other solvents. These techniques could be used to manipulate the Ole e 1 content in O. europaea extracts.
Insulin Delivery: How, When, and Where
Authors: David S. Schade, R. Philip Eaton
Journal: New England Journal of Medicine (1985)

With the discovery of insulin in 1921, many physicians thought that diabetes mellitus would become an easily treatable disease. This was not an unreasonable assumption, because other states of hormonal deficiency, including hypothyroidism, hypoadrenalism, and isolated growth hormone deficiency, have been "cured" with the discovery and availability of the missing hormone. In contrast, the discovery of insulin marked the beginning rather than the end of a major effort by many investigators to provide insulin to diabetic patients in a way that would correct the metabolic abnormalities of diabetes mellitus.Why has the method of insulin delivery become a major focus . . .
Isolation of Virus Related to SV40 from Patients with Progressive Multifocal Leukoencephalopathy
Authors: Leslie P. Weiner, Robert M. Herndon, Opendra Narayan, Richard T. Johnson, Keerti Shah, Lucien J. Rubinstein, Thomas J. Preziosi, Frances K. Conley
Journal: New England Journal of Medicine (1972)

Abstract Virus related to simian-virus 40 (SV40) was isolated from brains of two patients with progressive multifocal leukoencephalopathy, a human demyelinating disease. Virus was grown in cell cultures of primary African green-monkey kidney inoculated with cultures of cells derived from patients' brains. Electron microscopy showed virus-like particles resembling papovaviruses in the brain of one patient and in monkey-kidney cell cultures infected with both virus isolates. Immunologic studies using fluorescent and neutralizing antibodies indicate a close relation between the isolated viruses and SV40.
Anti-doping programme and physicians
Authors: Michael Petrou
Journal: British Journal of Sports Medicine (2011)

Lecture 1 The role of physicians in supporting athletes dates from the ancient times. Since the 18th century, it can be documented the role of physicians in the ‘doping’ of athletes with banned drugs. Today, even though governments, sport authorities and organised medicine abandon doping, a significant minority of physicians seem to continue playing a role in the doping of athletes. Several studies have shown that physicians are consulted by athletes and officials for advice on doping and the majority indicated not willing to prescribe doping substances without medical indication. Recent studies showed that the knowledge of the majority of physicians about doping agents and doping in general remains poor. Under the World Anti-Doping Program, the revised definition of doping includes physicians in the group of persons who can fulfil the elements of a doping offence. The Prohibited List clearly specifies the substances and methods prohibited in-, and out-of-competition while the International Standard for Therapeutic Use Exemption indicates the criteria for athletes who need, for therapeutic purposes, to use prohibited substances or methods. Through their unique relation with the athletes, physicians have an important role in discouraging doping in sport. For physicians, as with athletes, it is important to closely follow the changes on anti-doping regulations.
Reporting Risks and Benefits of Therapy by Use of the Concepts of Unqualified Success and Unmitigated Failure
Authors: G. B. John Mancini, Michael Schulzer
Journal: Circulation (1999)

The NNT (number needed to treat) and NNH (number needed to harm) are useful in conveying the results of clinical trials because they emphasize the effort that must be expended to accomplish a single, tangible outcome. But NNT conveys the effort required to achieve a positive outcome without distinguishing between the presence or absence of treatment-related adverse events. Similarly, NNH conveys harm without accounting for the achievement or lack of achievement of the benefit of therapy. Consequently, a mathematical model was developed to extend the NNT and NNH to represent the effort required to achieve "unqualified success" (NNTUS, treatment success without treatment-induced side effects) and "unmitigated failure" (NNHUF, lack of treatment success with treatment-induced side effects).NNTUS was calculated by adjusting the absolute risk reduction to allow for the probability of not incurring a treatment-related adverse event. NNHUF was similarly calculated by adjusting the absolute risk of incurring a treatment-related adverse event by the probability of not incurring any treatment-related benefit. The impact of conveying clinical trial data by the use of NNT, NNTUS, NNH, and NNHUF is illustrated by means of 11 highly cited trials identified systematically from the cardiovascular literature. The treatment effort measured by the NNTUS and the NNHUF was consistently higher than that given by the traditional NNT and NNH. These increments ranged from 1% to several hundred percent.The NNTUS and the NNHUF represent the treatment effort required on average to achieve 1 unqualified success and 1 unmitigated failure. NNTUS and NNHUF balance benefit and harm in an objective way and are relevant for making service delivery decisions.
SM-06 * DEXAMETHASONE USE DURING RADIOTHERAPY IN HIGH-GRADE GLIOMA: AN INSTITUTIONAL REVIEW
Authors: K. Pitter, E. Diamond, C. Brennan, Y. Yamada, T. Chan, E. Holland, K. Beal
Journal: Neuro-Oncology (2014)

BACKGROUND: Dexamethasone (DEX) is a mainstay in high-grade glioma (HGG) treatment due to the ability to decrease cerebral edema in the perioperative window and control neurological symptoms during adjuvant therapy. However, DEX has many potential systemic complications and there has been a recent effort at our hospital to more rigorously titrate DEX usage during radiotherapy (RT) with patient symptoms. The purpose of this study was to retrospectively evaluate DEX usage, readmissions, and subjective complaints during radiotherapy. METHODS: We performed an IRB-approved review of patients with pathologist-confirmed HGG from 2010-2013 to identify (i) the DEX dosage throughout RT, (ii) subjective patient complaints, specifically pertaining to fatigue, neuromotor, seizure, nausea, vomiting, headache, and vision, and (iii) readmissions during the treatment process, which are all documented during routine weekly status checks throughout the period of adjuvant RT. RESULTS: We identified 347 HGG patients treated at our institution. We saw no significant differences in pathology distribution, age, performance status, chemotherapy or antiangiogenic therapy use in 2013 compared to 2010-2012. However, 41% of patients in 2013 started RT without DEX, compared to 22% from 2010-2012 (p = .0005), with no increase in the number of patients requiring DEX later during RT to manage their symptoms. The mean total DEX dose during RT was significantly lower in 2013 (3.51 in 2013 vs 4.86 mg/day in 2010-2012, p = 0.0061). Although DEX usage was reduced, we observed no differences in readmissions (4% in 2013 vs 8% 2009-2012, p = 0.33) or subjective complaints (80% of patients in 2013 vs 83% in 2009-2012, p = 0.63). CONCLUSIONS: Our data suggests that HGG patients can be safely managed with lower DEX doses without increased adverse outcomes or patient readmissions. Further studies are needed to more systematically investigate DEX usage during HGG radiotherapy and whether long-term outcomes such as progression and survival are affected.
Autologous haematopoietic stem cell transplantation for Behcet's disease with pulmonary involvement: analysis after 5 years of follow up
Authors: B Maurer
Journal: Annals of the Rheumatic Diseases (2005)

Background: Myeloablative chemotherapy and autologous haematopoietic stem cell transplantation (HSCT) may provide a therapeutic option in severe Behçet's disease (BD) with pulmonary involvement. Case reports: Two patients with BD with pulmonary involvement refractory to conventional immunosuppressive treatment underwent HSCT 1999. Stem cells were mobilised with cyclophosphamide (2 and 4 g/m2) and subsequently enriched ex vivo for CD34+ cells. The conditioning regimen used was melphalan (200 mg/m2). Outcome was measured by improvement of clinical features, function of affected organs, serological markers, need for immunosuppressive chemotherapy after transplant, and relapse. In both cases HSCT was successful, with good response and without serious complications. After 5 years of follow up one patient is in complete remission without immunosuppressive drugs and one has partial remission, needing low dose corticosteroids (8 mg/day). Conclusion: In these two patients myeloablative chemotherapy, followed by HSCT could be performed safely with marked improvement. In comparison with other observational studies the duration of more than 5 years of remission is remarkable, and its full duration is still unknown.
Cholesterol and bile acid metabolism in cultures of primary rat bile ductular epithelial cells
Authors: Philip B. Hylemon, Patricia M. Bohdan, Alphonse E. Sirica, Douglas M. Heuman, Reno Z. Vlahcevic
Journal: Hepatology (1990)

The role of hepatocytes in bile acid and cholesterol metabolism has been extensively studied. By contrast, nothing is known about the role of bile ductular epithelial cells in cholesterol and bile acid metabolism. The purpose of the current studies was to establish whether bile ductular epithelial cells synthesize cholesterol, bile acids or both and to determine whether these cells are capable of metabolizing (hydroxylating, conjugating) bile acids. Bile ductular epithelial cells were isolated from rat liver after ligation of the common bile duct for 6 to 8 wk. Bile ductular epithelial cells were essentially free ( &gt; 99%) of hepatocytes and were histochemically positive ( &gt; 80%) for γ–glutamyl transpeptidase activity. Cholestatic hepatocytes were simultaneously isolated and characterized with regard to their ability to synthesize and metabolize bile acids. Incubation of bile ductular epithelial cells with [ 14 C] acetate resulted in rapid labeling of cellular cholesterol, suggesting that these cells have a complete cholesterol biosynthetic pathway. The addition of [4– 14 C]–cholesterol to bile ductular epithelial cells did not lead to detectable synthesis of [ 14 C]–bile acids. [24– 14 C]–Cholic acid, [24– 14 C]–deoxycholic acid, [24– 14 C]–lithocholic acid and [ 3 H]–ursodeoxycholic acid were individually added to bile ductular epithelial cells and incubated for 24 or 48 hr. Bile acid metabolites were extracted and separated by C–18 reverse–phase high performance liquid chromatography or thin–layer chromatography. Bile ductular epithelial cells conjugated deoxycholic acid, ursodeoxycholic acid and lithcholic acid to glycine and taurine. Surprisingly, no conjugation of cholic acid was detected. Conjugated lithocholic acid was further metabolized to highly polar metabolite(s), possibly β–muricholic acid. In contrast, cholestatic hepatocytes synthesized bile acid from exogenously added cholesterol. In addition, cholestatic hepatocytes converted deoxycholic acid to taurocholic acid and ursodeoxycholic acid and lithocholic acid to tauro–β–muricholic acid. We conclude that bile ductular epithelial cells differ significantly from the hepatocyte in regard to bile acid metabolism. Finally, we provide evidence that bile ductular epithelial cells can be used to study metabolic and transport processes occurring in the biliary tree.(HEPATOLOGY 1990;11:982–988.).
If She Had Only Been Batteyized.
Authors: C. M. Fenn
Journal: JAMA (1896)

San Diego, Cal., July 9, 1896. <h3>To the Editor:</h3> —Apropos of recent contributions to theJournalby Drs. Boal and Daniel suggesting castration as a punishment for certain derelicts (degenerates?) I enclose an excerpt from a reliable source: "Prof. Pellmann of Bonn University, who makes a special study of heredity, has been tracing the career of the descendants of Frau Ada Jurke, a notorious drunkard, who was born in 1740 and died in 1800. Her descendants have numbered 834, of whom 709 have been traced from youth by Prof. Pellmann. Of these, 7 were convicted of murder; 76 of other crimes; 142 were professional beggars; 64 lived on charity, and 181 women of the family led disreputable lives. The family has cost the German Government for maintenance and cost in the courts, almshouses and prisons, $1,250,000." The details are quite as startling as those connected with the history of a
Arthritis and primary biliary cirrhosis.
Authors: P Mills, R N MacSween, G Watkinson
Journal: BMJ (1977)

hypoxia and decreased renal perfusion so that urea formation is increased and excretion hindered.This could lead to a moderately elevated plasma urea and slightly elevated plasma creatinine, which might account for the apparently inferior dis- criminating power of the urea :creatinine ratio observed by your contributors when compared with the individual measurements of urea and creatinine.Incidentally, the correlation between plasma urea and creatinine in the 350 unselected patients may have been adversely affected if the authors included patients with ketoacidosis.It is well known that acetoacetate and acetone interfere in the Jaffe reaction for creatinine i and the plot of urea versus creatinine showed a number of points with seemingly disproportionate high creatinine concentrations.