tbuckley/cabot-search huggingface dataset:
Importance of the Kidney, Vessels, and Heart with Administration of β<sub>2</sub> Adrenergic Receptor Agonists in Patients Susceptible to Acute Respiratory Distress Syndrome
Authors: Eric M. Snyder, Bruce D. Johnson
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

From the Authors:

We thank Drs. Snyder and Johnson for their insightful interest in our recent trial article (1). We agree with them that there are many potentially important nonbronchodilator effects of β-agonists, including stimulation of alveolar fluid clearance, effects upon inflammatory cells, and potentially promoting alveolar epithelial repair responses via MMP-9 (2–5). The wealth of supporting data from translational and animal/preclinical studies drove the hypothesis that β-agonists might work as a therapeutic or preventative agent in patients with or at risk of acute respiratory disease (ARDS). Unfortunately, as has been so often the case with developing new strategies for therapy in ARDS, translation of these findings into clinical benefits has been unsuccessful, with the BALTI-2 study finding an increased risk of death in patients with ARDS treated with intravenous β-agonists (6).

In their elegant discussion, Snyder and Johnson suggest that deleterious effects of β-agonists upon the kidney may have counteracted any beneficial effects of β-agonists upon alveolar fluid clearance in patients with ARDS. We agree that the effects of β2-agonists upon renal sodium handling are important to consider. We reported no difference in daily fluid balance in the phase 2 BALTI-1 paper (7) but have no additional unpublished data from BALTI-2 (6) or BALTI-prevention (1) to help shed light on this action. However, we note that when intravenous β2-adrenergic agonists were used for tocolysis during pregnancy, they have been associated with reduced sodium, potassium, and water excretion, leading to a reduced hematocrit and intravascular hypervolemia (8, 9) and development of maternal pulmonary edema (10).

Finally, we suggest that, although our BALTI-prevention trial did not reduce the incidence of ARDS, we did demonstrate some findings worthy of future study. We found that inhaled salmeterol resulted in a reduction in systemic inflammation, which resulted in reduced alveolar epithelial barrier dysfunction perioperatively. The magnitude of the effects was not sufficient to prevent postoperative ARDS but did significantly reduce the incidence of reported postoperative pneumonia

We suggest, therefore, that salmeterol protected the alveolar epithelium in patients undergoing esophagectomy by reducing inflammatory and epithelial damage during injurious one-lung ventilation. We agree with Snyder and Johnson that combination therapies, targeting different mechanisms implicated in the development of ARDS, are likely to be needed to successfully treat and prevent ARDS.
Survey shows junior doctors are still overworked Government will commission research on NHS prescribing British tobacco curbs remain voluntary Health secretary promises blitz on practice paperwork Nurses can prescribe more medicines
Authors: L. Beecham
Journal: BMJ (1995)

The preliminary results from the BMA's nationwide survey of junior hospital doctors shows that 300 are still contracted to work more than 83 hours a week—the ceiling that should have been achieved by 1 April 1993. The Department of Health maintains that there are only four posts in Britain over 83 hours. The survey was conducted so that comparisons could be made with the results from the regional task forces. By 31 December 1994 no junior doctor on an on call rota in a hard pressed specialty should have been working more than 72 hours. The survey shows that 22.8% of juniors are still contracted to work above 72 hours.

The preliminary results are based on a random sample of 3500 responses spread across all specialties and all regions. The survey showed that 2.2% of senior registrars, 1.5% of registrars, 0.3% of senior house officers, and 1.3% of house officers were contracted to work more than 83 hours a week.

Almost 60% of junior doctors are working longer than their contracted hours. The majority of these extra hours are unpaid. The department's official data do not take account of these extra hours.

The results show that the take up rate of partial shifts, a working pattern introduced to help to reduce hours, has been low. Most doctors (68.5%) remain on the traditional working pattern of on call rotas; only 5.4% are on partial shifts.

The survey asked about intensity of work and the results show that juniors are not receiving adequate periods of rest. …
Association Between Licensure Examination Scores and Practice in Primary Care
Authors: Robyn Tamblyn
Journal: JAMA (2002)

Context Standards for licensure are designed to provide assurance to the public of a physician's competence to practice.However, there has been little assessment of the relationship between examination scores and subsequent practice performance.Objective To determine if there is a sustained relationship between certification examination scores and practice performance and if licensing examinations taken at the end of medical school are predictive of future practice in primary care.Design, Setting, and Participants A total of 912 family physicians, who passed the Que ´bec family medicine certification examination (QLEX) between 1990 and 1993 and entered practice.Linked databases were used to assess physicians' practice performance for 3.4 million patients in the universal health care system in Que ´bec, Canada.Patients were seen during the follow-up period for the first 4 years (1993 cohort of physicians) to 7 years (1990 cohort of physicians) of practice from July 1 of the certification examination to December 31, 1996.Main Outcome Measures Mammography screening rate, continuity of care index, disease-specific and symptom-relief prescribing rate, contraindicated prescribing rate, and consultation rate.Results Physicians achieving higher scores on both examinations had higher rates (rate increase per SD increase in score per 1000 persons per year) of mammography screening (␤ for QLEX, 16.8 [95% confidence interval {CI}, 8.7-24.9];␤ for Medical Council of Canada Qualifying Examination [MCCQE], 17.4 [95% CI, 10.6-24.1])and consultation (␤ for QLEX, 4.9 [95% CI, 2.1-7.8];␤ for MCCQE, 2.9 [95% CI, 0.4-5.4]).Higher subscores in diagnosis were predictive of higher rates in the difference between disease-specific and symptom-relief prescribing (␤ for QLEX, 3.9 [95% CI, 0.9-7.0];␤ for MCCQE, 3.8 [95% CI, 0.3-7.3]).Higher scores of drug knowledge were predictive of a lower rate (relative risk per SD increase in score) of contraindicated prescribing for MCCQE (relative risk, 0.88; 95% CI, 0.77-1.00).Relationships between examination scores and practice performance were sustained through the first 4 to 7 years in practice. ConclusionScores achieved on certification examinations and licensure examinations taken at the end of medical school show a sustained relationship, over 4 to 7 years, with indices of preventive care and acute and chronic disease management in primary care practice.
Abstract 3119: SIDT1 is a mediator of pro-desmoplastic pancreatic stellate-adenocarcinoma intercellular communication
Authors: Mark S. Duxbury, Jennifer Christie
Journal: Cancer Research (2011)

Abstract Introduction: Pancreatic adenocarcinoma is characterized by extensive collagen-rich but hypovascular desmoplasia that impairs drug delivery. Desmoplasia is driven by complex tumor-stromal interactions. Anti-desmoplastic strategies may improve therapeutic responses to existing agents. We examined the role of the membrane protein SIDT1 in mediating pro-desmoplastic signaling between tumor and stromal cells. Methods: Pancreatic stellate cells (PSC) and adenocarcinoma cells were isolated from surgical patients, characterised and maintained in culture. SIDT1 and collagen I expression was quantified by realtime PCR and Western blotting. SIDT1 fluorescence immunocytochemistry and immunohistochemistry was performed. Collagen I production was quantified in direct and indirect adenocarcinoma/PSC coculture. The effects of SIDT1 gene silencing on collagen I expression were examined using doxycycline-inducible shRNA generating vectors and compared to non-silencing control transfectants Results: SIDT1 is expressed at relatively high levels in PSC. Adenocarcinoma cells and patient specimens show heterogeneity in SIDT1 expression. Adenocarcinoma/PSC coculture enhances collagen I expression. SIDT1 gene silencing, but not control shRNA, attenuates collagen I production in direct but not indirect coculture. Conclusions: SIDT1 is abundant in PSC and variably expressed in patient samples. SIDT1 gene silencing limits collagen I production driven by contact dependent tumour-stromal intercellular communication. Disruption of SIDT1-dependent adenocarcinoma/PSC communication may represent a means of limiting desmoplasia. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3119. doi:10.1158/1538-7445.AM2011-3119
Stabilization of Atherosclerotic Plaques by Blockade of Macrophage Migration Inhibitory Factor After Vascular Injury in Apolipoprotein E–Deficient Mice
Authors: Andreas Schober, Jürgen Bernhagen, Michael Thiele, Ute Zeiffer, Sandra Knarren, Marion Roller, Richard Bucala, Christian Weber
Journal: Circulation (2003)

Macrophage migration inhibitory factor (MIF), a cytokine that controls cell-mediated inflammatory responses, is upregulated in atherogenesis; however, its functional contribution to lesion development has not been evaluated.We studied the role of MIF on neointima lesion formation after wire-induced injury of carotid arteries in apolipoprotein E-deficient (apoE(-/-)) mice. Immunohistochemistry revealed that MIF expression was detectable in endothelial cells before injury and upregulated in smooth muscle cells (SMCs) 24 hours after endothelial denudation. Three weeks after injury, MIF was predominantly found in endothelial cells and macrophage-derived foam cells. Neutralizing MIF with a monoclonal antibody resulted in a marked reduction of neointimal macrophages and inhibited transformation of macrophages into foam cells. Conversely, the content of SMCs and of collagen in the neointima were increased, amounting to a slight but not significant reduction in neointima and media size after 3 weeks of MIF monoclonal antibody treatment. Notably, serum levels of the cytokines IL-2, IL-4, IL-6, IL-10, and tumor necrosis factor were increased in MIF monoclonal antibody-treated mice. In vitro flow assays revealed that MIF pretreatment of aortic endothelium enhanced monocyte recruitment and that the monocyte arrest induced by oxidized LDL is mediated by endothelial MIF, as shown by monoclonal antibody inhibition.Inhibition of MIF resulted in a shift in the cellular composition of neointimal plaques toward a stabilized phenotype with reduced macrophage/foam cell content and increased SMC content. This might be attributable to a reduction of monocyte recruitment mediated by endothelial MIF.
Androgen Induction of the Androgen Receptor Coactivator Four and a Half LIM Domain Protein-2: Evidence for a Role for Serum Response Factor in Prostate Cancer
Authors: Hannelore V. Heemers, Kevin M. Regan, Scott M. Dehm, Donald J. Tindall
Journal: Cancer Research (2007)

Abstract Androgen receptor (AR) activity is critical for prostate cancer progression. Overexpression of several AR-associated coactivators has been shown to be essential for AR activation during disease progression. The stimuli and signaling pathways leading to overexpression of these coregulators, however, remain largely elusive. Here, we investigated whether androgen signaling, which demarcates critical transitions during prostate cancer disease progression, can affect coregulator expression. We found that expression of four and a half LIM domain protein-2 (FHL2), a key AR coactivator that is overexpressed in prostate cancer and associates with a poor prognosis, is induced strongly by androgens. Androgen induction of this coactivator established a feed-forward mechanism that robustly activated the AR. Stimulation of FHL2 after androgen exposure was time- and dose-dependent and relied on the presence of a functional AR. Androgen induction of FHL2 depended on active transcription of the FHL2 gene, mediated by action of serum response factor (SRF) on its proximal promoter. Loss of SRF, a transcription factor that preferentially regulates the expression of genes involved in mitogenic response and cytoskeletal organization, hampered prostate cancer cell proliferation. These results suggest a novel indirect mechanism of androgen action on FHL2 expression and provide evidence that SRF is an important determinant of AR action in prostate cancer cells. [Cancer Res 2007;67(21):10592–9]
Spinal Anesthesia for Hip Pinning Given With the Patient Supine
Authors: Alon P. Winnie
Journal: JAMA (1969)

It is common practice when administering a spinal anesthetic to a patient with a fractured hip to give the anesthetic to the patient before moving him or her to the fracture table. This requires that the patient then be moved to the fracture table shortly after a chemical sympathectomy. The result is an excessively high incidence of hypotension; in this elderly and frequently debilitated group of patients, hypotension all too often does irreparable damage. By administering the anesthetic to the patient on the fracture table, the need to move the patient after the onset of anesthesia is avoided. This simple change in technique has been shown to reduce the incidence of hypotension by more than two thirds and the mortality by more than one half.
Deletion of NEMO/IKKγ in Liver Parenchymal Cells Causes Steatohepatitis and Hepatocellular Carcinoma
Authors: Tom Luedde, Naiara Beraza, Vasileios Kotsikoris, Geert van Loo, Arianna Nenci, Rita De Vos, Tania Roskams, Christian Trautwein, Manolis Pasparakis
Journal: Cancer Cell (2007)
INCREASED VASCULAR PERMEABILITY INDUCED BY HUMAN PLASMIN
Authors: Oscar D. Ratnoff
Journal: The Journal of Experimental Medicine (1965)

Preparations of plasminogen, soluble in aqueous media, increased vascular permeability in guinea pig skin when activated by streptokinase or urokinase. The permeability-enhancing effect was inhibited by soybean trypsin inhibitor but not by triprolidine. Permeability-enhancing activity evolved when plasmin was incubated with fractions of plasma rich in prokinin. The experiments described suggest that plasmin exerts its permeability-increasing effect through the elaboration of kinins.
Science, Politics, and Radiation
Authors: Henry N. Wagner
Journal: JAMA (1988)

When a question involves radiation, science and politics meet. This has been true for some time in the United States and Europe, but activism is on the rise in other parts of the world as well. Now, intense debate about the siting of a low-level radioactive waste disposal site in Malaysia may force the closure of the Asian Rare Earth Company (ARE), which operates a plant that extracts rare earths from monazite sand, a residue of tin mining. A trial now under way in the high court of Ipoh has involved radiation experts and activists from all over the world, representing both (or all) sides of the nuclear issue. The ARE started operation in May 1982 as a joint venture between the Malaysians and the Japanese. The rare earths are shipped to Japan and eventually yield yttrium and other rareearth elements used in making televisions, computers, and steel. One of
Infection with Vancomycin-Resistant<i>Staphylococcus aureus</i>Containing the<i>vanA</i>Resistance Gene
Authors: Soju Chang, Dawn M. Sievert, Jeffrey C. Hageman, Matthew L. Boulton, Fred C. Tenover, Frances Pouch Downes, Sandip Shah, James T. Rudrik, Guy R. Pupp, William J. Brown, Denise Cardo, Scott K. Fridkin
Journal: New England Journal of Medicine (2003)

Vancomycin-resistant S. aureus was cultured from the exit site of a temporary dialysis catheter of a patient with diabetes, peripheral vascular disease, and persistent foot ulcers. The organism carried the vanA resistance gene, which may have come from the vancomycin-resistant Enterococcus faecalis that was also isolated from the patient, who had received vancomycin for several weeks.
Cyclophosphamide for Scleroderma Lung Disease
Authors: Fernando J. Martinez, W. Joseph McCune
Journal: New England Journal of Medicine (2006)

Clinically significant interstitial lung disease affects patients with systemic sclerosis (scleroderma) and is a cause of morbidity and mortality in approximately 40 percent of these patients.1 Management of this condition remains difficult and controversial.2,3 In this issue of the Journal, Tashkin and colleagues4 report the results of a multicenter, placebo-controlled trial of oral cyclophosphamide in patients with well-defined, symptomatic scleroderma-related interstitial lung disease and alveolitis. They document small but statistically significant improvements in lung function and symptoms with cyclophosphamide administered over the course of one year — the first positive results of a placebo-controlled trial in this field.How . . .
Response to Comment on “A Peptidomimetic Targeting White Fat Causes Weight Loss and Improved Insulin Resistance in Obese Monkeys”
Authors: Kirstin F. Barnhart, Dawn R. Christianson, Mikhail G. Kolonin, James F. Hulvat, Lawrence Chan, Wadih Arap, Renata Pasqualini
Journal: Science Translational Medicine (2012)

Several lines of evidence indicate that the effects of adipotide on weight loss and food consumption in obese monkeys are not due to a toxic effect, but rather result from the targeting mechanism of adipotide.
BETA-ADRENERGIC BLOCKING AGENTS IN THE TREATMENT OF CONGESTIVE HEART FAILURE: Mechanisms and Clinical Results
Authors: Robert Neil Doughty, MB MRCP FRACP, Norman Sharpe, MD FRACP FACC
Journal: Annual Review of Medicine (1997)

▪ Abstract Congestive heart failure is a major public health problem in Western countries. Despite current treatment including angiotensin converting enzyme inhibitors, mortality and morbidity remain high. The sympathetic nervous system is markedly activated in heart failure, and inhibition of this system with the beta-adrenergic blocking agents may provide further benefit. Several clinical trials involving over 3000 patients have shown that beta-blocker therapy improves left ventricular function in patients with heart failure. However, the effects of such therapy on symptoms and exercise tolerance have been variable. Recent reports have suggested that survival is improved with the beta-blocker carvedilol. Large-scale, long-term clinical trials are required to confirm these findings and to clearly define the role of this promising therapy for patients with heart failure.
Genetic Investigation of Adenylate Cyclase: Mutations in Mouse and Man
Authors: Z Farfel, M R Salomon, H R Bourne
Journal: The Annual Review of Pharmacology and Toxicology (1981)

As a pivotal control point in cardiovascular, neural, endocrine, and meta­ bolic regulation, hormone-sensitive adenylate cyclase serves as the target for drugs used in treating disorders of almost every organ system. How do drugs and hormones stimulate adenylate cyclase? The methods of molecu­ lar pharmacology and biochemistry have provided most of the experimental facts: Radioligand binding studies have allowed characterization of the molecular properties of membrane receptors and established that recep­ tors are physically separable from the catalytic unit that synthesizes cyclic adenosine 3',5'-monophosphate (cAMP) from ATP (1-5). Purifica­ tion of plasma membranes has allowed precise kinetic studies of regu­ lation of cAMP synthesis, and has led to the discovery that guanine nucleotides regulate both cAMP synthesis and binding of agonists to recep­ tors (6-10). For detailed accounts of the biochemical characterization of adenylate cyclase and possible interactions of its components in membranes, we refer the reader to several recent reviews (11-13). Here we review results of an experimental approach, based on the concepts and techniques of somatic genetics, that has contributed significantly to our current understanding of adenylate cyclase. This approach has helped to define a membrane protein,
Intrarenal Arteriovenous Fistula Simulating a Hypervascular Renal Tumor on Radionuclide Renal Imaging
Authors: EDWIN E. YEO, JAMES C. LOW
Journal: Clinical Nuclear Medicine (1995)

A 45-year-old man underwent Tc-99m DTPA studies for evaluation of hypertension. The early focal increased perfusion in the right kidney simulating a hypervascular tumor was found to be an intrarenal arteriovenous fistula at surgery.
Guarding against over-inclusive notions of “context”: Psycholinguistic and electrophysiological studies of specific context functions in schizophrenia
Authors: Debra Titone, J. Bruno Debruille
Journal: Behavioral and Brain Sciences (2003)

Abstract Phillips &amp; Silverstein offer an exciting synthesis of ongoing efforts to link the clinical and cognitive manifestations of schizophrenia with cellular accounts of its pathophysiology. We applaud their efforts but wonder whether the highly inclusive notion of “context” adequately captures some important details regarding schizophrenia and NMDA/glutamate function that are suggested by work on language processing and cognitive electrophysiology.
Surgical Treatment of Female Stress Urinary Incontinence with a Trans-Obturator-Tape (T.O.T.®) Uratape®: Short Term Results of a Prospective Multicentric Study
Authors: P Costa, P Grise, S Droupy, F Monneins, C Assenmacher, P Ballanger, J.F Hermieu, V Delmas, L Boccon-Gibod, C Ortuno
Journal: European Urology (2004)
Two Cases of Abdominal Operation in Early Childhood
Authors: F. Eve
Journal: BMJ (1897)

no further indication is required.In passing, it may be said that when this sodden appearance is present, and the knife cuts not crisply but as if passing through soaked blotting-paper, the opening thus made is frequently permanent, or at any rate remains for long periods; for the membrane has become so disorganised as to impair its tendency to repair.
Drug Gray Market
Authors: Mike Mitka
Journal: JAMA (2012)

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