tbuckley/cabot-search huggingface dataset:
Linezolid for Treatment of Chronic Extensively Drug-Resistant Tuberculosis
Authors: Myungsun Lee, Jongseok Lee, Matthew W. Carroll, Hongjo Choi, Seonyeong Min, Taeksun Song, Laura E. Via, Lisa C. Goldfeder, Eunhwa Kang, Boyoung Jin, Hyeeun Park, Hyunkyung Kwak, Hyunchul Kim, Han-Seung Jeon, Ina Jeong, Joon Sung Joh, Ray Y. Chen, Kenneth N. Olivier, Pamela A. Shaw, Dean Follmann, Sun Dae Song, Jong-Koo Lee, Dukhyoung Lee, Cheon Tae Kim, Veronique Dartois, Seung-Kyu Park, Sang-Nae Cho, Clifton E. Barry
Journal: New England Journal of Medicine (2012)

Linezolid has antimycobacterial activity in vitro and is increasingly used for patients with highly drug-resistant tuberculosis.We enrolled 41 patients who had sputum-culture-positive extensively drug-resistant (XDR) tuberculosis and who had not had a response to any available chemotherapeutic option during the previous 6 months. Patients were randomly assigned to linezolid therapy that started immediately or after 2 months, at a dose of 600 mg per day, without a change in their background regimen. The primary end point was the time to sputum-culture conversion on solid medium, with data censored 4 months after study entry. After confirmed sputum-smear conversion or 4 months (whichever came first), patients underwent a second randomization to continued linezolid therapy at a dose of 600 mg per day or 300 mg per day for at least an additional 18 months, with careful toxicity monitoring.By 4 months, 15 of the 19 patients (79%) in the immediate-start group and 7 of the 20 (35%) in the delayed-start group had culture conversion (P=0.001). Most patients (34 of 39 [87%]) had a negative sputum culture within 6 months after linezolid had been added to their drug regimen. Of the 38 patients with exposure to linezolid, 31 (82%) had clinically significant adverse events that were possibly or probably related to linezolid, including 3 patients who discontinued therapy. Patients who received 300 mg per day after the second randomization had fewer adverse events than those who continued taking 600 mg per day. Thirteen patients completed therapy and have not had a relapse. Four cases of acquired resistance to linezolid have been observed.Linezolid is effective at achieving culture conversion among patients with treatment-refractory XDR pulmonary tuberculosis, but patients must be monitored carefully for adverse events. (Funded by the National Institute of Allergy and Infectious Diseases and the Ministry of Health and Welfare, South Korea; ClinicalTrials.gov number, NCT00727844.).
FATAL INTERNAL INJURIES WITHOUT ASSOCIATED EXTERNAL MARKS
Authors: Frank R. Dutra
Journal: JAMA (1952)

In the investigation of deaths that have occurred unexpectedly and without reliable witnesses, autopsies not infrequently disclose cases in which unsuspected injuries were the proximal cause of death, even though there were no evidences of injury on the surface of the victim's body. Furthermore, the bodies of persons known to have died of traumatic injuries often bear insignificant or no external signs resulting from the fatal violence. It is probable that each year many unexpected or sudden deaths not due to natural causes are ascribed to such causes by coroners or attending physicians. Complete investigations, including medicolegal autopsies, doubtless would prove that the greatest proportion of these improperly certified fatalities were caused by injuries resulting from blunt force. Included in this group would be some instances in which beneficiaries had been deprived of insurance benefits because the traumatic nature of the death had not been recognized. In addition, a significant
Hydrogels in endovascular embolization. III. Radiopaque spherical particles, their preparation and properties
Authors: D. Horák, M. Metalová, F. Švec, J. Drobník, J. Kálal, M. Borovička, A.A. Adamyan, O.S. Voronkova, K.Z. Gumargalieva
Journal: Biomaterials (1987)
Influence of branched-chain amino acids and branched-chain keto acids on protein synthesis in isolated hepatocytes
Authors: Wolfgang Base, Carl Barsigian, Alisa Schaeffer, Ellen Shaw, Jose Martinez, Willis C. Maddrey
Journal: Hepatology (1987)

We investigated the effects of the branched-chain amino acids--valine, leucine and isoleucine--or their keto analogs, the branched-chain keto acids--alpha-ketoisovaleric acid, alpha-ketoisocaproic acid and alpha-keto-beta-methylvaleric acid--on protein synthesis and secretion by monolayers of rabbit hepatocytes incubated with [35S] methionine in pulse-chase and steady-state experiments. The branched-chain amino acids (2.0 mM or 1.0 mM), in the presence or absence of insulin (2 X 10(-4) IU per dish) and in both types of experiments, reduced the trichloroacetic acid-precipitable 35S-protein secreted into the medium. The branched-chain keto acids (2.0 mM or 1.0 mM) had a stimulatory effect on secreted trichloroacetic acid-precipitable 35S-protein which was observed only by the pulse-chase technique in the presence of insulin. Immunoaffinity chromatography of medium demonstrated a slight inhibition by branched-chain amino acids and a slight stimulation by branched-chain keto acids on secretion of 35S-albumin and no effect of either treatment on secretion of 35S-fibrinogen. ELISA analysis of total (i.e., 35S-labeled and unlabeled) secreted albumin revealed an inhibitory effect of the branched-chain amino acids in both pulse-chase and steady-state experiments, and a small stimulatory effect, in steady-state experiments, of the branched-chain keto acids; both effects were insulin-dependent. Total secreted fibrinogen, under steady-state conditions, was increased by the branched-chain keto acids in the presence of insulin, while transferrin production was unaffected by any treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Health Care Reform — Toward More Freedom, and Responsibility, for Physicians
Authors: Harold S. Luft
Journal: New England Journal of Medicine (2009)

In this Sounding Board article, the author proposes major reform of health care in the United States by means of establishing universal coverage pools to pay for hospitalizations and the management of chronic illness. Ambulatory care not related to chronic illness would be paid for through a system organized around primary care physicians and emphasizing economic incentives, flexibility, and choice for patients and providers.
Congenital pigment synthesizing melanoma of the scalp
Authors: Sook Jung Yun, Dong Kyun Han, Min-Cheol Lee, Jee-Bum Lee, Hee Jo Baek, Si Young Bae, Tai Ju Hwang, Sam Yong Lee, Joon Kyoo Lee, Hoon Kook
Journal: Journal of the American Academy of Dermatology (2010)
Modulation of human platelet protein kinase C by endotoxic lipid A.
Authors: J Grabarek, S Timmons, J Hawiger
Journal: Journal of Clinical Investigation (1988)

Lipid A is the toxic principle of lipopolysaccharide of gram-negative bacteria, which causes a spectrum of changes in blood cells and vascular cells. We now report that human platelets are directly stimulated by endotoxic lipid A that activates protein kinase C. Rapid phosphorylation of a human platelet protein of Mr 47,000, a marker of protein kinase C activation, accompanies secretion of [14C]serotonin and aggregation triggered by endotoxic lipid A. These events are time and concentration dependent, with phosphorylation reaching maximum in 2 min and the concentration of lipid A causing a 50% effect (EC50) between 12 and 15 microM. Phospholipase C activation in lipid A-stimulated platelets was not observed as judged by a lack of generation of [3H]diacylglycerol in [3H]arachidonic acid-labeled platelets and a lack of generation of [32P]-phosphatidic acid in 32PO4-labeled platelets. Lipid A did not induce formation of TXA2 as measured by radioimmunoassay for TXB2. The stimulation of human platelets and activation of protein kinase C by endotoxic lipid A was blocked by lipid X, a structural precursor of lipid A. Lipid X also blocked the stimulation of human platelets by phorbol 12-myristate 13-acetate, suggesting that lipid A, lipid X and phorbol ester share reactive site(s) on the human platelet membrane. Although lipid X inhibited thrombin-induced phosphorylation of P47 it did not suppress secretion of [14C]serotonin, indicating the role of protein kinase C-independent pathways in platelet stimulation by thrombin. The inhibitory effect of lipid X did not involve generation of cyclic AMP in human platelet membrane preparations. These results indicate that human platelets are stimulated by endotoxic lipid A, a naturally occurring biologic modifier of protein kinase C. Due to the widespread presence of this enzyme in blood cells, vascular cells, and neurons, its modulation by lipid A may represent a significant mechanism underlying hematologic and circulatory derangements observed in endotoxic shock in humans.
Disrupted Pulmonary Vasculature and Decreased Vascular Endothelial Growth Factor, Flt-1, and TIE-2 in Human Infants Dying with Bronchopulmonary Dysplasia
Authors: ABHAY J. BHATT, GLORIA S. PRYHUBER, HEIDIE HUYCK, RICHARD H. WATKINS, LEON A. METLAY, WILLIAM M. MANISCALCO
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

An abnormal pulmonary vasculature may be an important component of bronchopulmonary dysplasia (BPD). We examined human infant lung for the endothelial cell marker PECAM-1 and for angiogenic factors and their receptors. Lung specimens were collected prospectively at ∼ 6 h after death. The right middle lobe was inflation fixed and part of the right lower lobe was flash frozen. We compared lungs from infants dying with BPD (n = 5) with lungs from infants dying from nonpulmonary causes (n = 5). The BPD group was significantly more premature and had more days of ventilator and supplemental oxygen support, but died at a postconceptional age similar to control infants. PECAM-1 protein and mRNA were decreased in the BPD group. PECAM-1 immunohistochemistry showed the BPD group had decreased staining intensity and abnormal distribution of alveolar capillaries. The dysmorphic capillaries were frequently in the interior of thickened alveolar septa. The BPD group had decreased vascular endothelial growth factor (VEGF) mRNA and decreased VEGF immunostaining, compared with infants without BPD. Messages for the angiogenic receptors Flt-1 and TIE-2 were decreased in the BPD group. We conclude that infants dying with BPD have abnormal alveolar microvessels and that disordered expression of angiogenic growth factors and their receptors may contribute to these abnormalities.
Abstract 1664: A delicate balance between radiation-induced autophagy and apoptosis in HPV-positive head and neck cancer.
Authors: Tyler L. Fowler, Kai D. Ludwig, Reza Djavadian, Bryan P. Bednarz, Randall J. Kimple
Journal: Cancer Research (2013)

Abstract Purpose: The molecular mechanisms responsible for improved outcomes seen in patients with human papillomavirus (HPV) positive head and neck cancer (HNC) remain largely unknown. Ionizing radiation can induce autophagy, a genetically programmed, evolutionarily conserved response to stress whereby cellular constituents are engulfed, digested, and recycled to sustain cellular metabolism. We investigated whether radiation-induced cellular autophagy is modulated by HPV oncogenes leading to altered therapeutic responses between HPV+ and HPV- HNCs. Methods: An immortalized human tonsillar epithelial (HTE) cell line engineered to stably express LXSN vector alone, HPV-16 E6, or HPV-16 E7 was used for all experiments. All constructs received a single radiation dose of 4 Gy. Radiation survival was assessed by clonogenic survival. Activation of autophagy proteins LC3-A and LC3-B were analyzed at 4 and 24 hr time points using western blotting and fluorescence microscopy along with acridine orange staining. Apoptosis was evaluated by caspase activity at the same time points. Results: HPV-16 E6 resulted in greater sensitivity, while HPV-16 E7 resulted in radiation resistance relative to than control cells (surviving fraction after 4 Gy = 8.4+/-0.5% vs. 35+/-3.8% vs. 20+/-1.1%, respectively, 1way ANOVA p&amp;lt;0.0001). At baseline, expression of HPV-16 E6 had no affect on LC3-B expression while HPV-16 E7 and HPV-16 E6/E7 resulted in a significant increase in autophagy. Four hours following radiation, autophagy was increased in HPV-16 E6 (2.0 fold), E7 (2.6 fold) and E6/E7 (2.2 fold) expressing cells whereas vector and untransfected control cells showed no effect (1.2 and 1.1 fold, respectively). This increase was maximal at 4 hrs and had returned to baseline 24 hrs after radiation. No significant change in apoptosis was seen 4 hrs following radiation, but a gradual increase was seen between 12 and 48 hrs. Conclusions: The HPV oncoproteins E7 up regulates autophagic pathways at baseline correlating with radiation resistance. Four hours following radiation, both E6 and E7 result in significant upregulation of autophagy. This is followed by upregulation of apoptosis, suggesting a transition from an initial protective response to cellular death. Citation Format: Tyler L. Fowler, Kai D. Ludwig, Reza Djavadian, Bryan P. Bednarz, Randall J. Kimple. A delicate balance between radiation-induced autophagy and apoptosis in HPV-positive head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1664. doi:10.1158/1538-7445.AM2013-1664
Bone loss and glucocorticoid therapy in patients with respiratory disease
Authors: A. Fairney
Journal: Thorax (1999)

Background.Osteoporosis is a common complication of long-term glucocorticoid therapy for which there is no well-proved preventive or restorative treatment.Methods.We carried out two 48-week, randomized, placebo-controlled studies of two doses of alendronate in 477 men and women, 17-83 years of age, who were receiving glucocorticoid therapy.The primary end point was the difference in the mean percent change in lumbar-spine bone density from base line to week 48 between the groups.Secondary outcomes included changes in bone density of the hip, biochemical markers of bone turnover, and the incidence of new vertebral fractures.Results.The mean (±SE) bone density of the lumbar spine increased by 2.1±0.3 percent and 2.9±0.3 percent, respectively, in the groups that received 5 and 10 mg of alendronate per day (P<0.001)and decreased by 0.4±0.3percent in the placebo group.The femoral-neck bone density increased by 1.2±0.4percent and 1.0±0.4percent in the respective alendronate groups (P<0.01) and decreased by 1.2±0.4percent in the placebo group (P<0.01).The bone density of the trochanter and total body also increased significantly in the patients treated with alendronate.There were proportionally fewer new vertebral fractures in the alendronate groups (overall incidence, 2.3 percent) than in the placebo group (3.7 percent) (relative risk, 0.6; 95 percent confidence interval, 0.1 to 4.4).Markers of bone turnover decreased significantly in the alendronate groups (P<0.001).There were no differences in serious adverse effects among the three groups, but there was a small increase in nonserious upper gastrointestinal effects in the group receiving 10 mg of alendronate.Conclusions.Alendronate increases bone density in patients receiving glucocorticoid therapy.
Screening Young Men for Chlamydial Infection
Authors: Mark D. Aronson
Journal: JAMA (1993)

<i>Chlamydia trachomatis</i>is a major cause of sexually transmitted diseases (STDs). In the era of the acquired immunodeficiency syndrome, it is easy to lose sight of the damage done by this vexing organism. Chlamydial diseases mimic those caused by the more virulent gonococcus, such as urethritis and pelvic inflammatory disease. Because the acute illnesses<i>Chlamydia</i>produces are generally less severe than gonococcal diseases,<i>Chlamydia</i>is more likely to escape detection. Chlamydial disease may remain asymptomatic but still result in chronic infection and, in women, scarring of the fallopian tubes, leading to infertility and ectopic pregnancy. In men, infection causes urethritis, epididymitis, and possibly infertility.<sup>1</sup> See also pp 2057, 2065, and 2071. Chlamydial infection is most often asymptomatic in women.<sup>2</sup>Less well known is the observation that asymptomatic infection is also common in men.<sup>3</sup>Because asymptomatic or minimally symptomatic men could serve as an important reservoir for the
Identification of alpha 1-adrenergic receptors on sarcolemma from normal subjects and patients with idiopathic dilated cardiomyopathy: characteristics and linkage to GTP-binding protein.
Authors: T Vago, M Bevilacqua, G Norbiato, G Baldi, E Chebat, P Bertora, G Baroldi, R Accinni
Journal: Circulation Research (1989)

Discontinuous density sucrose gradient centrifugation was used to isolate membrane vesicles from the left ventricle of three normal subjects (one prospective organ donor and two traffic victims whose hearts were obtained 1 hour after death) and nine patients undergoing cardiac transplantation as a consequence of idiopathic dilated cardiomyopathy. Sarcolemma-enriched subcellular fractions, detected in the interface between 8.55% and 25% sucrose, were identified by the increased activity of Na+,K+-ATPase and by enrichment in beta-adrenergic receptor density. The density of beta-adrenergic receptors was lower in vesicles from diseased hearts (610 +/- 71 fmol/mg protein) than in vesicles from normal hearts (1,410 +/- 226 fmol/mg protein; p less than 0.01). alpha 1-Adrenergic receptors were identified in these membrane vesicles by [3H]prazosin binding. Specific binding of [3H]prazosin was about 50% of the total binding at 1 nM, and alpha 1-adrenergic binding sites were saturable at approximately 3 nM. Scatchard analysis revealed 58 +/- 5 fmol/mg protein (KD = 0.90 +/- 0.08 nM) in pathological hearts and 30 +/- 5 fmol/mg protein (KD = 0.90 +/- 0.03 nM) in normal hearts (p less than 0.01). The displacement curve of (-)-norepinephrine in membrane vesicles from normal hearts delineated one subpopulation of alpha 1-adrenergic receptors; the addition of 0.1 mM GTP did not cause right shift. In membrane vesicles from diseased heart, the displacement curve of (-)-norepinephrine disclosed two subpopulations of alpha 1-adrenergic receptors. A right shift that occurred after addition of GTP showed that in this case alpha 1-adrenergic receptors were functionally coupled with GTP-binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Echinocandins — An Advance in the Primary Treatment of Invasive Candidiasis
Authors: Thomas J. Walsh
Journal: New England Journal of Medicine (2002)

Candida species are now the fourth leading cause of nosocomial bloodstream infection in the United States, exceeded in some series only by Staphylococcus aureus, coagulase-negative staphylococcus, and enterococcus species.1,2 Wey and colleagues estimate the attributable mortality of candidemia at 38 percent.3 Candidemia is a surrogate marker for the presence of deeply invasive candidiasis, particularly in immunocompromised hosts.4 In patients with untreated or inadequately treated candidemia, the rate of clinically overt complications, including endophthalmitis, endocarditis, septic arthritis, and renal candidiasis, may be as high as 15 percent. Candidemia may be complicated by chronic disseminated candidiasis in neutropenic hosts and by . . .
Abstract 708: A novel hedgehog signaling inhibitor blocks hedgehog-mediated carcinogenesis
Authors: Jingwu Xie, Eric Qipeng Fan, Chelsea Schelgel, Xiaoli Zhang, Massound Garrisson, Miao He
Journal: Cancer Research (2010)

Abstract The link of hedgehog (Hh) signaling activation to human cancer and synthesis of a variety of Hh signaling inhibitors raise great expectation that inhibiting Hh signaling may be effective in human cancer treatment. We have developed a novel hedgehog signaling inhibitor Cyc-T, which has better solubility and higher efficacy in inhibiting hedgehog signaling. In analyses of motor neuron differentiation and osteoblast differentiation, we found that Cyc-T is very effective in preventing hedgehog-mediated functions. Using a mouse model based on keratin 14 promoter-driven expression of an activated form of SMO, SmoM2, we found that a cyclopamine derivative cyc-T are effective in shrinkage of Smo-mediated tumors. K14cre/R26SMOm2yfp mice develop skin dysplasia on postnatal day 3 and BCC-like tumors by day 15. We performed topical application of cyclopamine or its derivatives CPA006, Cyc-T on the skin of K14cre/R26SMOm2yfp mice daily for seven days with the solvent ethanol as the control. The effects of these reagents on the tumors were examined by histological examination of skin biopsies and expression of Hh target genes. In comparison with the control group, we found that 6 out of 9 mice treated with cyclopamine reduced tumor mass and decreased expression of Hh target genes. The mice with no effects by cyclopamine and its derivatives had no changes in Hh target gene expression. In an orthotopic mouse model of pancreatic cancer, we measured the tumor progression following drug treatment and obtained promising results. Taken together, we discovered that Cyc-T are an effective inhibitor for Hh signaling-mediated carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 708.
Exercise and Decreased Risk of NIDDM
Authors: E S Horton
Journal: New England Journal of Medicine (1991)

Although the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) is not fully understood, it is clear that at least three factors are important: a genetic predisposition to the disease; a decrease in the action of insulin in insulin-sensitive tissues, including adipose tissue, skeletal muscle, and the liver; and a defect in pancreatic β-cell function.1 Conditions associated with the development of insulin resistance increase the risk of NIDDM greatly. Chief among these are obesity and advancing age. More recently, it has been recognized that hypertension may be associated with resistance to insulin and hyperinsulinemia.2 So, too, may be the increase in plasma . . .
Difficulties in giving fully informed consent
Authors: R. G Jepson
Journal: BMJ (2003)

Ten ways to improve information technology in the NHS Users, not geeks, should design interfaceEditor-With reference to the article by Majeed et al, 1 the consultation is central to medicine, and information technology must facilitate it.With the constant changes in information technology it remains nascent, disjointed, and user hostile.It is no surprise that implementation remains problematic.Paper records will be superseded, but successors must emulate their familiarity and simplicity.The authors do not mention the main weakness-what users see and what they can do with it.Background issues (coding, networks, intranets, security, maintenance, data transfer, etc) are the province of geeks.Even the brand leader (EMIS) is difficult to operate in consultation, and its presentation of data, especially lab results, is dire.Interfaces operated by hand via large colour liquid crystal display touch screens are the technologies that can transform health computing by rendering the consultation process "natural."Healthcare computing will be wonderful when the user can use it easily.Get users, not geeks, to design the interface, and the project will take wing.
New types of Paps and puffs
Authors: Douglas Kamerow
Journal: BMJ (2007)

In the US liquid-based cytology for cervical screening has replaced conventional cytology in many settings. Although there has been a lot of research on the liquid-based technology, few randomized trials have appeared. Two studies, an editorial, and a commentary in this issue add to the confidence that a move to liquid-based techniques is of both clinical and programmatic benefit.

Guglielmo Ronco and colleagues randomized over 45 000 women to receive either …