tbuckley/cabot-search huggingface dataset:
Suppressed smooth muscle proliferation and inflammatory cell invasion after arterial injury in elafin-overexpressing mice
Authors: Syed H.E. Zaidi, Xiao-Mang You, Sorana Ciura, Stacey O’Blenes, Mansoor Husain, Marlene Rabinovitch
Journal: Journal of Clinical Investigation (2000)

Elastases degrade the extracellular matrix, releasing growth factors and chemotactic peptides, inducing glycoproteins such as tenascin, and thereby promoting vascular cell proliferation and migration. Administration of serine elastase inhibitors reduces experimentally induced vascular disease. The ability to mount an intrinsic anti-elastase response may, therefore, protect against intimal/medial thickening after vascular injury. To investigate this, we showed that wire-induced endothelial denudation of the carotid artery is associated with transient elevation in elastase activity and confirmed that this is abolished in transgenic mice overexpressing the serine elastase inhibitor, elafin, targeted to the cardiovascular system. Ten days after injury, nontransgenic littermates show vessel enlargement, intimal thickening, increased medial area and cellularity, and 2-fold increase in tenascin. Injured vessels in transgenic mice become enlarged but are otherwise similar to sham-operated controls. Injury-induced vessel wall thickening, which is observed only in nontransgenic mice, is related to foci of neutrophils and macrophages, in addition to smooth muscle cells that fail to stain for α-actin and are likely dedifferentiated. Our study therefore suggests that a major determinant of the vascular response to injury is the early transient induction of serine elastase activity, which leads to cellular proliferation and inflammatory cell migration.
Persistent Photoaggravated Cutaneous Eruption Induced by Imipramine
Authors: William G. Walter-Ryan
Journal: JAMA (1985)

<h3>To the Editor.—</h3> Cutaneous reactions to tricyclic antidepressant drugs include acneiform eruptions, seborrheic dermatitis, contact dermatitis, nonspecific pruritic eruptions, urticaria, and photosensitivity reactions.<sup>1,2</sup>Most of these conditions are benign and self-limited. Although transient photosensitivity reactions have been documented with tricyclics, as well as with the structurally related phenothiazines,<sup>3</sup>persistent light-sensitive cutaneous reactions seem to be rare. We report a case of severe, persistent cutaneous photosensitivity induced by imipramine. <h3>Report of a Case.—</h3> A 38-year-old physically healthy white woman was treated with the tricyclic doxepin for symptoms of depression and anxiety occurring two years prior to the present illness. A transient rash appeared following the first dose and this drug was discontinued. Treatment with the tetracyclic antidepressant maprotiline and a benzodiazepine was uneventful. Four days prior to this admission, imipramine, 75 mg at bedtime, was prescribed after a long medication-free interval. The morning after the second dose, the patient
The pulmonary physician in critical care * Illustrative case 5: HIV associated pneumonia
Authors: R J Boyton
Journal: Thorax (2003)

The case history is presented of a patient with HIV associated pneumonia who was successfully treated in the ICU. The mortality rate of HIV infected patients admitted to the ICU has improved since the introduction of prophylaxis for Pneumocystis carinii pneumonia and highly active antiretroviral therapy (HAART). The identification of objective outcome predictors will help clinicians to decide when to pursue aggressive treatment and when to withhold or withdraw it.

An estimated 36 million people worldwide are currently infected with HIV, about 1.46 million in North America and Western Europe and a further 25.3 million in sub-Saharan Africa.1 An estimated 30 000 adults and children became infected with HIV in Western Europe during the year 2000. The continuing rate of infection, coupled with longer survival due to primary and secondary prophylaxis against opportunistic infection and highly active antiretroviral therapy (HAART), has resulted in the prevalence continuing to increase.1,2

Infection with HIV is associated with increased susceptibility to opportunistic infection with more than 100 viruses, bacteria, protozoa and fungi.3 Primary and secondary prophylaxis against opportunistic infections and HAART has led to changes in the nature, incidence, and presentation of opportunistic infections such as Pneumocystis carinii pneumonia (PCP), Mycobacterium avium intracellulare (MAI) , and cytomegalovirus (CMV) retinitis.2,4 New challenges are presented to physicians in medical high dependency units (HDUs) and intensive care units (ICUs). We report a patient who presented with HIV associated pneumonia and discuss the issues concerning admission to HDU/ICU of HIV infected individuals in the PCP prophylaxis and post-HAART era, drawing together current views of prognostic indicators and outcomes.

A 39 year old white man presented with a 3 week history of increasing shortness of breath accompanied by a non-productive cough, fever, and 5 kg weight loss. A diagnosis of HIV infection with …
Intravenous thrombolytic therapy with a combination of single-chain urokinase-type plasminogen activator and recombinant tissue-type plasminogen activator in acute myocardial infarction.
Authors: C Bode, G Schuler, T Nordt, S Schönermark, H Baumann, G Richardt, R Dietz, V Gurewich, W Kübler
Journal: Circulation (1990)

The effects of simultaneous intravenous infusions of 12 mg recombinant tissue-type plasminogen activator (rt-PA) over 30 minutes and 48 mg single-chain urokinase-type plasminogen activator (scuPA) over 40 minutes were studied in 38 patients with acute myocardial infarction. Coronary arterial patency was assessed angiographically 60 minutes and 90 minutes after initiation of treatment. Patency was achieved in 19 of 31 patients (61.3%) (95% confidence limits, 42-78%) at 60 minutes and in 27 of 33 patients (81.8%) (95% confidence limits, 65-93%) at 90 minutes. Nonspecific plasminogen activation was monitored by measuring relevant plasma parameters. At 60 minutes and 120 minutes, the fibrinogen concentration decreased slightly to 82.8 +/- 24.3% and 91.2 +/- 17.4% of the preinfusion level, and the plasminogen concentration to 66.3 +/- 15.2% and 65.3 +/- 13.4%, respectively. A greater consumption of alpha 2-antiplasmin was observed, which decreased to 30.7 +/- 22.8% and 32.2 +/- 21.2% of the preinfusion level at 60 and 120 minutes, respectively. No bleeding necessitating transfusion was observed. Two patients (5.3%) died during hospitalization. The findings suggest that the combined intravenous infusion of rt-PA and scuPA at appropriate doses induces highly effective coronary thrombolysis equal to the best results obtained with either rt-PA or scuPA alone. This efficacy is coupled with high specificity. Thus, the data support the potential use of combinations of rt-PA and scuPA in place of monotherapy.
Attacks on NHS staff increasing, MPs say
Authors: O. Dyer
Journal: BMJ (2003)

The British government is failing to meet self imposed targets on reducing attacks on NHS staff, a report published this week by the Parliamentary committee has said.

The House of Commons Public Accounts Committee said that the number of reported incidents is “clearly going in the wrong direction,” with nurses at particularly high risk.

According to the British crime survey 2000, nurses run a 5% risk of being violently assaulted at work in a given year, compared with 1.2% for the average worker. The risk for other healthcare workers, including doctors, …
Neuromuscular and vascular hamartoma of the small intestine: is it Crohn's disease?
Authors: N A Shepherd, J R Jass
Journal: Gut (1987)

Neuromuscular and vascular hamartoma has been described as a specific, if rare, stricturing condition of the small intestine. In this paper four cases with very similar macroscopic and histological features to those described as 9neuromuscular and vascular hamartoma9 are presented. In three of the patients there was an earlier histologically proven diagnosis of Crohn9s disease of the small intestine. We believe that 9neuromuscular and vascular hamartoma9 is not a hamartomatous condition but may be seen as part of the histological spectrum of Crohn9s disease, possibly in a chronic and 9burnt out9 phase. Indeed the presence of these changes may provide additional evidence for the diagnosis of Crohn9s disease.
Treatment of Transfusion-Transmitted Babesiosis by Exchange Transfusion
Authors: George A. Jacoby, Jettie V. Hunt, Katharine S. Kosinski, Zareh N. Demirjian, Charles Huggins, Paul Etkind, Leonard C. Marcus, Andrew Spielman
Journal: New England Journal of Medicine (1980)

BABESIOSIS is a malaria-like illness produced by tick-borne protozoa that can cause a spectrum of disease in human beings, varying from subclinical infection to severe febrile illness with hemolytic anemia, hemoglobinuria, and renal failure.1 , 2 The severest symptoms, and some fatal cases, have occurred in splenectomized persons. Effective chemotherapy is lacking. Babesia microti is the responsible agent in Massachusetts. It is transmitted by Ixodes dammini ticks.3 , 4 Feral mice are reservoir hosts.5 Transmissibility of B. microti by inoculation of infected human blood into hamsters and the occurrence of asymptomatic cases in human beings has led to the expectation that transfusion-induced babesiosis would . . .
US doctors identify top five activities that can be reduced
Authors: B. Roehr
Journal: BMJ (2011)

Doctors in the US could cut back on many common medical activities, such as imaging and routine antibiotics, without adversely affecting patient care to save substantial costs, says a survey by the National Physicians Alliance. The group now plans to educate doctors and patients on why this constitutes good medical practice.

The alliance, whose aim is to achieve high quality affordable healthcare for all, set up working groups in family, internal, and paediatric medicine to evaluate common medical activities. The groups looked at the frequency with which they engaged in a particular activity in their practice, the potential impact of that activity on quality and cost of care, the evidence supporting use of the activity, …
1062. Intracerebellar Injection of AAV-IGF-1 Improves Motor Function and Extends Survival in a Mouse Model of Amyotrophic Lateral Sclerosis
Authors: James C. Dodge, Marco A. Passini, Jennifer Clarke, Liza Grissett, Soo Hyun Kim, Rita Wen, Tatyana V. Taksir, Denise A. Griffiths, Seng H. Cheng, Brian K. Kaspar, Lamya S. Shihabuddin
Journal: Molecular Therapy (2006)

Amytrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by a selective loss of motor neurons in the motor cortex, brain stem and spinal cord. The etiology of motor neuron degeneration remains largely unknown. Although chronic delivery of therapeutic agents to the central nervous system has proven to be difficult, recent studies have demonstrated that intramuscular delivery of adeno-associated viral vectors encoding insulin growth factor 1 (AAV-IGF-1) slowed disease progression and extended survival in SOD1G93A mice. The efficacy of viral mediated expression of IGF-1 was mediated in part by the ability of the viral vector to undergo retrograde transport from muscle to motor neurons. Previously we demonstrated that targeting the deep cerebellar nuclei (DCN) of the cerebellum with viral vectors capable of axonal transport resulted in detection of transgene protein in both the brain stem and spinal cord (Dodge et al. 2005, PNAS 102:17822-17827). In this experiment we evaluated the efficacy of bilateral delivery of AAV1–IGF-1 and AAV2-IGF-1 to the DCN in 90 day old SOD1G93A mice. Starting at 80 days of age (and every 10 days thereafter), SOD1G93A mice underwent behavioral testing (rotarod, hindlimb and forelimb grip strength) to assess motor function. At 90 days of age (i.e., time point at which SOD1 mice exhibit overt disease symptoms of ALS) mice received stereotaxic bilateral injections of AAV1-IGF-I (n=26), AAV2-IGF-I (n=27), AAV1-GFP (n=26) or AAV2-GFP (n=25) aimed at the deep cerebellar nuclei (DCN) of the cerebellum. We found that bilateral delivery of AAV- IGF-1 treatment (regardless of serotype) to the DCN significantly promoted motor neuron survival, improved motor performance in both rotarod and grip strength behavioral tests and significantly extended lifespan (i.e., 12 day extension for AAV1-IGF-1 and 14 day extension for AAV2-IGF-1). Treatment with AAV-GFP had no effect on any of the parameters mentioned above. Our results indicate that direct administration of AAV-IGF-1 into the DCN modifies disease progression in a mouse model of ALS and that targeting the DCN with AAV vectors is an effective approach for delivering therapeutic transgenes to both the brain and spinal cord for the treatment of ALS.
Ascites in cirrhosis: A medical or surgical problem?
Authors: Leroy Shear
Journal: Hepatology (1990)

Fifty–seven cirrhotic patients with intractable ascites had a portosystemic shunt. In 35 patients, a peritoneovenous shunt had previously failed. Forty–six patients were in Pugh's class B and 11 were in class C. There were three operative deaths (5.3%). Fifty–three (98.2%) of the 54 survivors were cleared of ascites. In one patient, ascites persisted because of postshunt heart failure that resulted in a marked increase of caval pressure. Twenty–seven patients (50%) had late encephalopathy, which was severe and disabling in 12 (22%). One–and three–year survival rates were 72% and 36%, respectively. These results suggest that although portosystemic shunts are remarkably effective in dealing with ascites, the high rate of postoperative encephalopathy is a strong argument against their routine use in the management of intractable ascites in cirrhosis.
Endobronchial metastasis from renal adenocarcinoma simulating a foreign body.
Authors: E Amer, J Guy, B Vaze
Journal: Thorax (1981)

A patient was seen with right lower lobe collapse which partially re-expanded after removal of an endobronchial mass, initially thought to be a foreign body. The pathology revealed clear cell carcinoma identical with the primary removed from his kidney three years before.
Pharmacist fined for cheap drug charges
Authors: O. Dyer
Journal: BMJ (1995)

A pharmacist in Gwent who was fined £550 last week for refusing to levy NHS prescription charges on cheap drugs will take his case to Europe if the Welsh Office does not overturn the ruling against him. Allan Sharpe, owner of Sharpe the Chemist in Newbridge on Usk, has been treating NHS prescriptions for paying patients as private prescriptions if the drug costs less than the standard £5.25 charge.

Mid-Glamorgan Family Health Services Authority and Gwent Health Commission, which launched the original complaint against Mr Sharpe, have refused to comment to the press. The disciplinary tribunal told him that his …
Characteristics and Prognosis of Lone Atrial Fibrillation
Authors: Frederick N. Brand
Journal: JAMA (1985)

In 30 years of follow-up of 5,209 participants in the Framingham Study, 193 men and 183 women developed atrial fibrillation (AF). Among this group, "lone" AF occurred in 32 men and 11 women free of coronary heart disease, congestive heart failure, rheumatic heart disease, and hypertensive cardiovascular disease. To determine the characteristics and prognosis of lone AF, each case was matched to controls in the remaining Framingham sample. Comparisons indicated that levels of several risk factors associated with coronary heart disease were similar between the two groups. Atrial fibrillation cases, however, had significantly higher rates of preexisting nonspecific T- or ST-wave abnormalities and intraventricular block as determined by electrocardiograms. Follow-up for new cardiovascular events indicated similar rates of coronary heart disease and congestive heart failure, but the rate of strokes was significantly greater in the lone AF group. Findings suggest that subjects with lone AF, despite similar cardiovascular risk profiles to normal controls, have a distinct preponderance of preexisting electrocardiographic abnormalities. Furthermore, contrary to general belief, lone AF is not a benign condition; it has a serious prognosis, indicating a greater need for detection and treatment. (<i>JAMA</i>1985;254:3449-3453)
Cross-Talk between Estrogen Receptor and Epidermal Growth Factor Receptor in Head and Neck Squamous Cell Carcinoma
Authors: Ann Marie Egloff, Mary E. Rothstein, Raja Seethala, Jill M. Siegfried, Jennifer Rubin Grandis, Laura P. Stabile
Journal: Clinical Cancer Research (2009)

This study aimed to characterize estrogen receptor expression and signaling in head and neck squamous cell carcinoma (HNSCC) cell lines and patient tissues, and to evaluate estrogen receptor and epidermal growth factor (EGF) receptor (EGFR) cross-activation in HNSCC.Estrogen receptor expression and signaling in HNSCC cell lines were assessed by immunoblotting. In vitro proliferation and invasion were evaluated in HNSCC cell lines in response to estrogen receptor and EGFR ligands or inhibitors. Estrogen receptor and EGFR protein expression in patient tissues was assessed by immunohistochemical staining.Phospho-mitogen-activated protein kinase (P-MAPK) levels were significantly increased following combined estrogen and EGF treatment. Treatment of HNSCC cells with estrogen and EGF significantly increased cell invasion compared with either treatment alone, whereas inhibiting these two pathways resulted in reduced invasion compared with inhibiting either pathway alone. EGFR (P = 0.008) and nuclear estrogen receptor alpha (ER alpha(nuc); P < 0.001) levels were significantly increased in HNSCC tumors (n = 56) compared with adjacent mucosa (n = 30), whereas nuclear estrogen receptor beta (ER beta(nuc)) levels did not differ (P = 0.67). Patients with high ER alpha(nuc) and EGFR tumor levels had significantly reduced progression-free survival compared with patients with low tumor ER alpha(nuc) and EGFR levels (hazards ratio, 4.09; P = 0.01; Cox proportional hazards). In contrast, high ER beta(nuc) tumor levels were not associated with reduced progression-free survival alone or when combined with EGFR.ER alpha and ER beta were expressed in HNSCC, and stimulation with estrogen receptor ligands resulted in both cytoplasmic signal transduction and transcriptional activation. Estrogen receptor and EGFR cross-talk was observed. Collectively, these studies indicate that estrogen receptor and EGFR together may contribute to HNSCC development and disease progression.
Inherited disorder of purine metabolism. Correlation between central nervous system dysfunction and biochemical defects
Authors: F. M. Rosenbloom
Journal: JAMA (1967)

Children with an X-linked neurological disease often classed as cerebral palsy show an absence of an enzyme of purine metabolism, hypoxanthine-guanine phosphoribosyltransferase (PRTase), in the brain, liver, fibroblasts, and erythrocytes. The absence in these patients of PRTase activity in the basal ganglia where the enzyme is normally of highest activity can be correlated with the fact that the major clinical symptoms are attributable to basal ganglia dysfunction. The concentration of oxypurines (hypoxanthine and xanthine) in the cerebrospinal fluid (CSF) was four times normal and was greater than in plasma, which suggests that the brain also has an increased purine synthesis. The possible role of high oxypurine concentration in CSF in development of the neurological disease has been discussed. Treatment with allopurinol produced a further increase in the concentration of oxypurines in CSF.
Enzyme-linked immunosorbent assay detects a potential soluble form of the erythropoietin receptor in human plasma
Authors: Kevin W. Harris, John C. Winkelmann
Journal: American Journal of Hematology (1996)

The erythropoietin receptor (EpoR) is a type I transmembrane protein that is a member of the family of hemopoietin receptors. Several members of this family have soluble receptor forms that are secreted by the cells rather than expressed on the cell surface. An alternatively spliced EpoR transcript has been described in human erythroid precursors that, if translated, would produce a truncated, soluble EpoR lacking the transmembrane domain. To determine if the human EpoR is expressed in a soluble form, we developed a sensitive enzyme-linked immunosorbent assay (ELISA) for the EpoR, and we analyzed human serum and plasma. Sheep were immunized with a fusion protein (EREx) consisting of glutathione-S-transferase (GST) and the human EpoR extracellular domain. The sheep antiserum was affinity-purified on immobilized EREx, and then used in a two-stage antigen capture ELISA. The plasma from 20 normal subjects was studied with this assay. There was wide variability in the levels of soluble EpoR in these subjects (range, <10–2,200 ng/ml). An average value of 550 ± 735 ng/ml for soluble EpoR was obtained in these normals. Protein A adsorption of the test plasma prior to the assay had no effect on the values obtained. Assay of serum from the same normal subjects showed an average decrease of 88% in soluble EpoR levels compared to plasma. There was no correlation between hematocrit and soluble EpoR level. This assay may have utility in the further elucidation of erythropoietin physiology. © 1996 Wiley-Liss, Inc.
Abstract 903: Expression of estrogen receptor beta together with aromatase predicts survival in non-small cell lung cancer
Authors: Vei Mah, Diana Marquez, Mohammad Alavi, Erin L. Maresh, Nam Yoon, Steve Horvath, Lora Bagryanova, Michael Fishbein, David Chia, Richard Pietras, Lee Goodglick
Journal: Cancer Research (2011)

Abstract Lung cancer continues to be the leading cause of cancer mortality. There is increasing evidence suggesting estrogens and estrogen signaling play a significant role in lung cancer pathophysiology. Estrogen receptors (ER) alpha and beta are expressed in normal lung and many non-small cell lung cancers. Previously we found that in women 65 years and older with non-small cell lung cancer (NSCLC), higher aromatase levels in tumor cells conferred a worse prognosis for survival. Here we examine whether ER alpha and ER beta levels in conjunction with aromatase can further define different patient groups with respect to survival outcomes and possible treatment regimens. Methods: Immunohistochemistry was performed on a high-density tissue microarray with marker data and clinical information available for 378 patients. Patients were subcategorized by gender, age, smoking status and tumor histology. Survival data was determined using the Cox proportional hazards model and Kaplan-Meier curves. Results: Unlike aromatase, neither ER alpha nor ER beta alone were predictors of survival in NSCLC patients or any subset of these patients examined. However, when coupled with aromatase expression, higher ER beta levels predicted poorer survival in those patients whose tumors expressed higher levels of aromatase. Although this survival difference was present in patients of both genders, it was more pronounced in women &amp;gt; 65 years old, where higher expression of both ER beta and aromatase showed a markedly worse survival rate than that determined by aromatase alone. Conclusion: Combined expression of ER beta with aromatase has predictive value for survival in different gender and age subgroups of NSCLC patients. This predictive value is stronger than each individual marker alone. These results suggest that possibly treatment with aromatase inhibitors alone or combined with estrogen receptor modulators may have benefit in some subpopulations of NSCLC patients. 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 903. doi:10.1158/1538-7445.AM2011-903