tbuckley/cabot-search huggingface dataset:
A Critical Evaluation of New Agents for the Treatment of Sepsis
Authors: Roger C. Bone
Journal: JAMA (1991)

<h3>Objective.</h3> —To evaluate new treatments directed against endotoxin, tumor necrosis factor α, and interleukin 1 for use in sepsis and related disorders (sepsis syndrome and septic shock). <h3>Data Sources.</h3> —Investigations of these treatments in animal models, healthy human volunteers, and patients with sepsis and related disorders. <h3>Study Selection.</h3> —Particular attention was paid to studies of patients with sepsis and related disorders, especially randomized, double-blind, controlled trials. <h3>Data Extraction.</h3> —Animal studies and investigations with human volunteers were judged by how closely the experimental model replicated the clinical disorder (sepsis). Patient trials were assessed by sample size and design. Results of all studies were used to evaluate the likelihood that a given treatment would reduce mortality. <h3>Data Synthesis.</h3> —Direct comparison of E5 and HA-1A antibody studies is difficult because of differences in their design, definitions of shock, and methods of subgroup analysis. However, both antibodies improve outcome in some subgroups: E5 benefits patients with gram-negative infection (bacteremic or focal) who do not have refractory shock, and HA-1A benefits those with gramnegative bacteremia (regardless of whether shock is present) but not those with focal gram-negative infection. Two agents that may be beneficial in gram-positive and gram-negative infection are monoclonal antibodies to tumor necrosis factor α and receptor antagonists to interleukin 1. Preliminary results with both are reviewed. <h3>Conclusions.</h3> —All three types of treatment may improve outcome in sepsis. The best results will probably be obtained with combination therapy that interrupts multiple points of the inflammatory cascade underlying sepsis. (JAMA. 1991;266:1686-1691)
Divergent Haplotypes and Human History as Revealed in a Worldwide Survey of X-Linked DNA Sequence Variation
Authors: M. K. Shimada, K. Panchapakesan, S. A. Tishkoff, A. Q. Nato, J. Hey
Journal: Molecular Biology and Evolution (2006)

The population genetic history of a 10.1-kbp noncoding region of the human X chromosome was studied using the males of the HGDP-CEPH Human Genome Diversity Panel (672 individuals from 52 populations). The geographic distribution of patterns of variation was roughly consistent with previous studies, with the major exception that 1 highly divergent haplotype (haplotype X, hX) was observed at low frequency in widely scattered non-African populations and not at all observed in sub-Saharan African populations. Microsatellite (short tandem repeat) variation within the sequenced region was low among copies of hX, even though the estimated time of ancestry of hX and other sequences was 1.44 Myr. The estimated age of the common ancestor of all hX copies was 5,230 years (95% consistency index: 2,000–75,480 years). To further address the presence of hX in Africa, additional samples from Chad and Tanzania were screened. Five additional copies of hX were observed, consistent with a history in which hX was present in Africa prior to the migration of modern humans out of Africa and with eastern Africa being the source of non-African modern human populations. Taken together, these features of hX—that it is much older than other haplotypes and uncommon and patchily distributed throughout Africa, Europe, and Asia—present a cautionary tale for interpretations of human history.
α-Adrenergic Blockade Improves Recovery of Myocardial Perfusion and Function After Coronary Stenting in Patients With Acute Myocardial Infarction
Authors: Luisa Gregorini, Jean Marco, Michaela Kozàkovà, Carlo Palombo, Gian Battista Anguissola, Isabelle Marco, Monique Bernies, Bernard Cassagneau, Alessandro Distante, Irene M. Bossi, Jean Fajadet, Gerd Heusch
Journal: Circulation (1999)

Background —AMI reperfusion by thrombolysis does not improve TIMI flow and LV function. The role of infarct-related artery (IRA) stenosis and superimposed changes in coronary vasomotor tone in maintaining LV dysfunction must be elucidated. Methods and Results —Forty patients underwent diagnostic angiography 24 hours after thrombolysis. Seventy-two hours after thrombolysis, the culprit lesion was dilated with coronary stenting. During angioplasty, LV function was monitored by transesophageal echocardiography. Percent regional systolic thickening was quantitatively assessed before PTCA, soon after stenting, 15 minutes after stenting, and after phentolamine 12 μg/kg IC (n=10), the α 1 -blocker urapidil 600 μg/kg IV (n=10), or saline (n=10). Ten patients pretreated with β-blockers received urapidil 10 mg IC. Coronary stenting significantly improved thickening in IRA-dependent and in non–IRA-dependent myocardium (from 27±15% to 38±16% and from 40±15% to 45±15%, respectively). Simultaneously, TIMI frame count decreased from 39±11 and 40±11 in the IRA and non-IRA, respectively, to 23±10 and 25±7 ( P &lt;0.05). Fifteen minutes after stenting, thickening worsened in both IRA- and non–IRA-dependent myocardium (to 19±14% and 28±14%, P &lt;0.05), and TIMI frame count returned, in both the IRA and non-IRA, to the values obtained before stenting. Phentolamine and urapidil increased thickening to 36±17% and 41±14% in IRA and to 48±11% and 49±17% in non-IRA myocardium respectively, and TIMI frame count decreased to 16±6 and to 17±5, respectively. Changes were attenuated with β-blocker pretreatment. Conclusions —Our finding that α-adrenergic blockade attenuates vasoconstriction and postischemic LV dysfunction supports the hypothesis of an important role of neural mechanisms in this phenomenon.
COMPARISON OF LIPID CONTROL AMONG DIABETICS WITH NONCORONARY ATHEROSCLEROTIC VASCULAR DISEASE VERSUS CORONARY ARTERY DISEASE
Authors: Rashmi Thapa, Suresh Sharma, Vinodh Jeevanantham, Casper Hu, Taylor Myers, James Vacek, Buddhadeb Dawn, Kamal Gupta
Journal: Journal of the American College of Cardiology (2014)
Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine.
Authors: H W Murray, B Y Rubin, C D Rothermel
Journal: Journal of Clinical Investigation (1983)

We have found that the crude lymphokines, which prime the human monocyte-derived macrophage to generate H2O2 and exert microbicidal activity against intracellular Leishmania donovani, are rich in interferon (IFN)-gamma (600-3,000 U/ml). To determine the role of this specific lymphocyte product in macrophage activation, lymphokines were pretreated with a monoclonal antibody that neutralizes human IFN-gamma. Antibody exposure completely abolished the capacity of both mitogen- and antigen-stimulated lymphokines to either enhance macrophage H2O2 release or induce leishmanicidal activity. In addition, partially purified and pure recombinant human IFN-gamma were as effective as crude lymphokines in activating macrophages, and 3 d of treatment with 300 U/ml resulted in a seven- to eightfold increase in H2O2 generation and the intracellular killing of both L. donovani promastigotes and amastigotes. The ability of crude lymphokines to induce monocytes and macrophages from a patient with chronic granulomatous disease to kill L. donovani promastigotes was similarly abrogated by anti-IFN-gamma antibody, and could also be achieved by IFN-gamma alone. These results suggest that IFN-gamma is the key macrophage-activating molecule present within human lymphokines, and indicate that IFN-gamma can enhance both the oxygen-dependent and -independent antiprotozoal mechanisms of human mononuclear phagocytes.
Oral Administration of Aureomycin in the Treatment of Urinary Infections
Authors: Alexander M. Rutenburg, Fritz B. Schweinburg
Journal: New England Journal of Medicine (1949)

IN A previous communication1 intramuscular injection of aureomycin hydrochloride was reported to be not only a highly effective antibiotic in a variety of urinary infections but also, in many cases, curative after other antibiotics had failed. Owing to the pain caused by the intramuscular injections, even when the drug is given in a 1 or 2 per cent procaine solution, a subsequent series of 26 patients were treated by aureomycin given orally.ObservationsThese cases comprised an unselected group of 26 acute and chronic urinary infections and included 5 with chronic renal insufficiency. Seventeen patients had had prior treatment with . . .
Soluble Tapasin Restores MHC Class I Expression and Function in the Tapasin-Negative Cell Line .220
Authors: Paul J Lehner, Michael J Surman, Peter Cresswell
Journal: Immunity (1998)

Tapasin forms a bridge between TAP (transporters associated with antigen processing) and MHC class I molecules and plays a critical role in class I assembly. In its absence, TAP and class I do not associate, and class I cell surface expression is reduced. We now identify two independent functions for tapasin. Tapasin increases TAP levels and allows more peptide to be translocated to the endoplasmic reticulum. Furthermore, when expressed in the tapasin-negative .220 cell line, recombinant soluble tapasin retains its association with class I and restores class I cell surface expression and function, even though it no longer binds TAP or increases TAP levels. This finding suggests that the association of tapasin with class I is sufficient to facilitate loading and assembly of class I molecules.
WHO confirms avian flu infections in Canada
Authors: Barbara Kermode-Scott
Journal: BMJ (2004)

Canada has ordered the slaughter of about 19 million birds, including chickens, turkeys, ducks, geese, and pigeons, at 20 poultry farms in an effort to eradicate an outbreak of bird influenza. The World Health Organization has confirmed that there have been two human cases of avian influenza A (H7) in British Columbia, Canada. Both cases were mild.

On the basis of epidemiological information provided by Health Canada, WHO has raised the global pandemic preparedness level for the Canadian outbreak from 0.1 to 0.2—the same level as the global preparedness level for the avian flu outbreak …
Surgeon accused of operating beyond his competence
Authors: O. Dyer
Journal: BMJ (2001)

A consultant surgeon who left five women dead and seven more injured was accused before the General Medical Council this week of performing operations for which he had no training or experience and of misleading patients' families about the botched outcomes.

Steven Walker, 44, has been suspended on full pay of £55 000 ($77 000) since January 1999 from his job as a consultant general surgeon at the Victoria Hospital, Blackpool. After a hospital review of 140 of his …
TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell–mediated pathology
Authors: Mandy J McGeachy, Kristian S Bak-Jensen, Yi Chen, Cristina M Tato, Wendy Blumenschein, Terrill McClanahan, Daniel J Cua
Journal: Nature Immunology (2007)
Cure, Care, and Commitment: What Can We Look Forward To?
Authors: Robert Rizza, David Eddy, Richard Kahn
Journal: Diabetes Care (2008)

The prevalence of diabetes continues to increase at an alarming rate, with more than 9% of all adults and 20% of adults ≥60 years of age diagnosed with the disease (1). When those with impaired fasting glucose are added, about a third of the adult U.S. population has abnormal glucose metabolism. Equally alarming is that the cost of diabetes in 2007 was $175 billion, which includes $116 billion in excess medical expenditures and $58 billion in reduced national productivity (2). Thus, diabetes is a major, costly, and growing cause of morbidity and mortality in America. What should we be doing about this serious situation?

There are three obvious answers. First, we must redouble our efforts to find a cure for diabetes. This will take more research dollars invested into novel and imaginative ideas that explore the underlying cause of diabetes. Second, we must do whatever we can to reduce the likelihood that someone will develop diabetes. Although 100% effective prevention is not immediately in reach, there are many recent developments that hold great promise. Third, we must treat aggressively those who have or will develop diabetes to prevent the complications of diabetes from occurring. Despite the availability of a wide variety of glucose-lowering drugs and other relevant medications, supplies, devices, and well-established treatment guidelines (3,4), the majority of those affected by diabetes are not meeting the goals of therapy (5).

If diabetes can be cured or prevented or if the quality of care delivered to people with diabetes uniformly achieves recommended goals, undoubtedly there would be a major reduction in morbidity, mortality, and costs. If the impact of a cure for diabetes could be quantified, perhaps policy makers would be convinced that investing in diabetes research is not only the right thing to do, but the smart …
Scrotal Pathology as the Cause for Hip Pain
Authors: DOUGLAS H. SHEAFOR&spar;, LAWRENCE E. HOLDER, DAVID THOMPSON, DONALD S. SCHAUWECKER, GINA L. SAGER, EDWARD G. McFARLAND
Journal: Clinical Nuclear Medicine (1997)

Scrotal scintigraphy has become a relatively uncommon examination in many nuclear medicine departments. However, scrotal perfusin is visualized during three-phase bone imaging of the pelvis and hips. The authors present a compilation of three cases of hip pain secondary to unsuspected scrotal pathology documented on routine three-phase bone scintigraphy, discussing this topic for the first time in the literature. A short review of the pathophysiology of referred hip pain, differential diagnosis, and imaging alternatives emphasize the unique contribution of nuclear imaging.
Acute and Chronic Angiotensin-1 Receptor Antagonism Reverses Endothelial Dysfunction in Atherosclerosis
Authors: Abhiram Prasad, Theresa Tupas-Habib, William H. Schenke, Rita Mincemoyer, Julio A. Panza, Myron A. Waclawin, Samer Ellahham, Arshed A. Quyyumi
Journal: Circulation (2000)

Background —The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The present study was performed to determine whether angiotensin-1 (AT 1 ) receptor inhibition improves endothelial dysfunction. Methods and Results —In the femoral circulation of 19 patients with atherosclerosis and of 9 control subjects, we studied microvascular responses to reactive hyperemia, angiotensin II, acetylcholine, and sodium nitroprusside before and after the administration of intra-arterial losartan (10 mg). Femoral artery flow velocity was measured with a Doppler flow wire, and the femoral vascular resistance index (FVRI) was calculated as mean arterial pressure divided by flow velocity. Losartan induced a minor (5.9±2%, P =0.02) reduction in FVRI and inhibited angiotensin II–mediated vasoconstriction in both patient groups ( P &lt;0.01). After the administration of losartan, acetylcholine-mediated vasodilation was augmented in patients (44±5% to 58±4% reduction in FVRI with infusion at a rate of 150 μg/min, P &lt;0.001) but not control subjects. Vasodilation during reactive hyperemia was also greater after AT 1 receptor inhibition ( P =0.03) in patients, but the response to sodium nitroprusside remained unchanged. In a separate group of 31 patients with atherosclerosis, we investigated the effect of 8 weeks of oral losartan therapy on brachial artery flow-mediated vasodilation with the use of high-resolution ultrasound. Oral losartan therapy improved flow-mediated brachial artery dilation (1.4±0.9% to 3.2±0.8%, P =0.03) but had no effect on the nitroglycerin response. Serum nitrogen oxide levels increased from 21.6±1.7 to 26.7±2.4 μmol/L ( P =0.008). Conclusions —The results of the present study indicate that inhibition of the AT 1 receptor in patients with atherosclerosis reverses endothelial dysfunction by improving NO availability and therefore may have long-term therapeutic benefits.
Intrapulmonary and intramyocardial gene transfer in rhesus monkeys (Macaca mulatta): Safety and efficiency of HIV-1-derived lentiviral vectors for fetal gene delivery
Authors: Alice F. Tarantal, Ruth J. McDonald, Daniel F. Jimenez, C. Chang I. Lee, Cristin E. O'Shea, Alyssa C. Leapley, Rosa H. Won, Charles G. Plopper, Carolyn Lutzko, Donald B. Kohn
Journal: Molecular Therapy (2005)

Fetal gene transfer was studied using intrapulmonary and intramyocardial transfer of SIN HIV-1-derived lentiviral vectors expressing EGFP in rhesus monkeys. Fetuses were monitored sonographically during gestation and tissue analyses performed at term or 3 months postnatal age. Animals remained healthy during the study period as evidenced by normal growth, development, hematology, clinical chemistry, echocardiography, and pulmonary function tests. Strong pulmonary fluorescence was observed postnatally after fetal intrapulmonary delivery of lenti-CMV, but not lenti-SP-C, and compared to nontransferred controls. High EGFP copy numbers were found by quantitative PCR with both vector constructs in lung lobes (≤15%) and EGFP copies were also detected in the diaphragm, pericardium, and thorax. No differences were found in lung:body weight ratios, percentage lung parenchyma, or overall morphology when compared to controls. For intramyocardial gene delivery, strong transgene expression was found within the myocardium and pericardium, and high EGFP copy numbers were found by quantitative PCR (3–36%). EGFP was also detected in the aorta, thorax, and diaphragm. These studies indicate that postnatal heart and lung development and function were not altered after fetal intraorgan gene transfer and subsequent transgene expression prenatally and postnatally, and gene transfer was restricted to the thoracic cavity with intrapulmonary and intramyocardial lentiviral vector-mediated gene delivery.
Chemoreflex Drive and the Dynamics of Ventilation and Gas Exchange during Exercise at Hypoxia
Authors: Yoshiyuki Fukuoka, Masako Endo, Yasuharu Oishi, Haruo Ikegami
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

We tested the hypothesis that the promotion of hypoxic ventilatory responsiveness (HVR) and/or hypercapnic ventilatory responsiveness (HCVR) mostly acting on the carotid body with a changing work rate can be attributed to faster hypoxic ventilatory dynamics at the onset of exercise. Eleven subjects performed a cycling exercise with two repetitions of 6 minutes while breathing at FIO2 = 12%. The tests began with unloaded pedaling, followed by three constant work rates of 40%, 60%, and 80% of the subject's ventilatory threshold at hypoxia. Reference data were obtained at the 80% ventilatory threshold work rate during normoxia. Using three inhaled 100% O2 breath tests, a comparison of hypoxia and normoxia revealed an augmentation of HVR in hypoxia, which then significantly increased proportionally with the increase in work rate. In contrast, HCVR using three inhaled 10% CO2 breath tests was unaffected by the difference in work rate at hypoxia but did exceed its level at normoxia. The decrease in the half-time of hypoxic ventilation became significant with an increase in work rates and was significantly lower than at normoxia. Using a multiregression equation, HVR was found to account for 63% of the variance of hypoxic ventilatory dynamics at the onset of exercise and HCVR for 9%. O2 uptake on-kinetics and off-kinetics under hypoxic conditions were significantly slower than under normoxic conditions, whereas they were not altered by the changing work rates at hypoxia. These results suggest that the faster hypoxic ventilatory dynamics at the onset of exercise can be mostly attributed to the augmentation of HVR with an increase in work rates rather than to HCVR. Otherwise, O2 uptake dynamics are affected by the lower O2, not by the changing work rates under hypoxic conditions.
Phase II Trial of Weekly Paclitaxel in Patients With Previously Treated Advanced Urothelial Cancer
Authors: David J. Vaughn, Catherine M. Broome, Maha Hussain, John C. Gutheil, Avi B. Markowitz
Journal: Journal of Clinical Oncology (2002)

PURPOSE: We evaluated the efficacy and toxicity of weekly paclitaxel in patients with previously treated advanced urothelial cancer. PATIENTS AND METHODS: Patients with urothelial cancer who had received one prior systemic chemotherapy regimen for advanced disease and had evidence of disease progression were eligible for enrollment. Patients received paclitaxel 80 mg/m2 by 1-hour intravenous infusion weekly. A cycle of therapy consisted of four weekly treatments. RESULTS: The study enrolled 31 patients. Mean age was 66 years, and 45% of patients had three or more involved metastatic sites. Only 26% of patients had responded to prior chemotherapy. The median number of cycles delivered was three (range, one to eight) at a mean weekly paclitaxel dose of 79 mg/m2. Three patients achieved a partial response (10%; 95% confidence interval, 0% to 20%). Median time to progression was 2.2 months, and median overall survival time was 7.2 months. Therapy was well tolerated with minimal hematologic toxicity. Grade 3 nonhematologic toxicities were also uncommon. CONCLUSION: Although the overall response rate to weekly paclitaxel in patients with previously treated advanced urothelial cancer was modest, the chemotherapy-refractory nature of the study population should be considered.
Health Care Workers Infected With the Human Immunodeficiency Virus
Authors: Bernard Lo
Journal: JAMA (1992)

The tragedy of five patients who contracted human immunodeficiency virus (HIV) infection from a seropositive dentist has alarmed the public. The Centers for Disease Control (CDC) recently revised its recommendations for preventing the transmission of HIV infection to patients during invasive procedures. The CDC abandoned a previous plan to list exposure-prone invasive procedures that HIV-infected health care workers should not perform. The CDC said "expert review panels" should decide on a case-by-case basis whether seropositive health care workers may perform invasive procedures. As of February 1992, the revised recommendations were under review by the US Department of Health and Human Services. Many issues remain to be clarified, such as how these panels will operate and whether decisions will be consistent in similar cases. Disregarding the CDC guidelines or infection-control precautions may further erode public trust and lead to draconian restrictions on HIV-infected health care workers. Physicians and dentists should respond more effectively to public fears about HIV transmission. The challenge is to protect patients while respecting the privacy and livelihood of health care workers.
Transplacental Transfer of Bishydroxycoumarin in the Human
Authors: Parvin Saidi
Journal: JAMA (1965)

TRANSPLACENTAL transfer of the active agent in spoiled sweet clover hay was suggested by Schofield in 1924, even before bishydroxycoumarin (Dicumarol) was isolated. He demonstrated that spoiled sweet clover fed to pregnant cows could lead to abortion or death of the newborn calf from hemorrhage. Quick in 1946 found a hemorrhagic tendency and a prolonged prothrombin time in newborn pups from mothers receiving bishydroxycoumarin. A similar effect was also demonstrated in newborn rabbits by Kraus et al in 1949. Mahairas and Weingold<sup>1</sup>noted several reports of fetal or neonatal death with multiple hemorrhages after the administration of bishydroxycoumarin to pregnant human females. In other reports the drug was found harmless even during labor. Theoretically, the small molecular weight of bishydroxycoumarin (336.29) should facilitate its transfer across the placenta by simple diffusion, while its high degree of binding to serum albumin<sup>2</sup>should have the opposite effect. To our knowledge