tbuckley/cabot-search huggingface dataset:
Tissue Plasminogen Activator Inhibition in Diabetes Mellitus
Authors: Michael Small, Cornelius Kluft, Angus C MacCuish, Gordon D O Lowe
Journal: Diabetes Care (1989)

Depression of fibrinolysis may be relevant to the vascular complications of diabetes mellitus. Plasminogen activator inhibitor (PAI) is an important inhibitor of fibrinolysis in humans, and we have found basal activities of PA inhibition to be elevated in patients with diabetes compared with a reference group of healthy subjects (mean +/- SD 268 +/- 268 vs. 105 +/- 48%; P less than .0001). With a monoclonal antibody, it was shown that high inhibition values were due to PAI-1. No differences in PA inhibition were noted in relation to type of diabetes, diabetic treatment, or presence or absence of vascular complications. Basal PA inhibition did not correlate with in vivo (B beta 15-42 antigen) or ex vivo (fibrin plate) fibrinolytic activity or HbA1. In patients with non-insulin-dependent diabetes mellitus, treatment with the anabolic steroid stanozolol significantly reduced PA inhibition. These findings suggest a further abnormality of fibrinolysis in diabetes, but the lack of a relationship among other measures of fibrinolysis renders its biologic significance uncertain.
Targeting of HPV-16+ Epithelial Cancer Cells by TCR Gene Engineered T Cells Directed against E6
Authors: Lindsey M. Draper, Mei Li M. Kwong, Alena Gros, Sanja Stevanović, Eric Tran, Sid Kerkar, Mark Raffeld, Steven A. Rosenberg, Christian S. Hinrichs
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The E6 and E7 oncoproteins of HPV-associated epithelial cancers are in principle ideal immunotherapeutic targets, but evidence that T cells specific for these antigens can recognize and kill HPV+ tumor cells is limited. We sought to determine whether TCR gene engineered T cells directed against an HPV oncoprotein can successfully target HPV+ tumor cells. Experimental Design: T-cell responses against the HPV-16 oncoproteins were investigated in a patient with an ongoing 22-month disease-free interval after her second resection of distant metastatic anal cancer. T cells genetically engineered to express an oncoprotein-specific TCR from this patient's tumor-infiltrating T cells were tested for specific reactivity against HPV+ epithelial tumor cells. Results: We identified, from an excised metastatic anal cancer tumor, T cells that recognized an HLA-A*02:01–restricted epitope of HPV-16 E6. The frequency of the dominant T-cell clonotype from these cells was approximately 400-fold greater in the patient's tumor than in her peripheral blood. T cells genetically engineered to express the TCR from this clonotype displayed high avidity for an HLA-A*02:01–restricted epitope of HPV-16, and they showed specific recognition and killing of HPV-16+ cervical, and head and neck cancer cell lines. Conclusions: These findings demonstrate that HPV-16+ tumors can be targeted by E6-specific TCR gene engineered T cells, and they provide the foundation for a novel cellular therapy directed against HPV-16+ malignancies, including cervical, oropharyngeal, anal, vulvar, vaginal, and penile cancers. Clin Cancer Res; 21(19); 4431–9. ©2015 AACR.
Effect of Anticancer Chemotherapeutic Agents on Immune Reactions of Mice. I. Comparison of Two Nitrosoureas: 1,3-Bis(2-chloroethyl)-1-nitrosourea and 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea 2
Authors: Abdul Ghaffar, Wolf Lichter, Larry L. Wellham, M. Michael Sigel
Journal: JNCI Journal of the National Cancer Institute (1978)

With the use of male (C57BL/6 × DBA/2)F1 mice and female DBA/2 mice, immunosuppressive actions of two nitrosoureas were compared. The results indicated that 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) suppressed anti-sheep red blood cell (SRBC) plaque-forming cell responses when it was injected before or after the primary immunization (>90%) with SRBC's and suppressed secondary responses when it was injected after primary immunization (50%) with SRBC's or before (80%) or after (60%) the secondary challenge. In contrast, 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Me-CCNU) caused a suppression (70%) only when injected before the secondary challenge. BCNU and Me-CCNU both inhibited blastogenic responses to lipopolysaccharide and concanavalin A (Con A) when tested 2 days after treatment, but the magnitude of suppression was far greater with BCNU (>90%) than with Me-CCNU (50%). Furthermore, the recovery from suppression of blastogenic response to Con A was earlier after Me-CCNU treatment (7 days) than after BCNU treatment (>9 days). Both BCNU and Me-CCNU suppressed immediate hypersensitivity and, in most mice, augmented delayed hypersensitivity responses to SRBC's. Neither BCNU nor Me-CCNU significantly altered antibody-dependent cell-mediated cytotoxicity against chicken erythrocytes. The two drugs differed in their immunosuppressive action on anti-SRBC humoral responses and blastogenic responses to mitogens, and in these assays Me-CCNU had a considerably less immunosuppressive effect than did BCNU.
Maintenance immunosuppressive therapy with everolimus preserves humoral immune responses
Authors: Geertrude H. Struijk, Robert C. Minnee, Sven D. Koch, Aeilko H. Zwinderman, Karlijn A M I van Donselaar-van der Pant, Mirza M. Idu, Ineke J M ten Berge, Frederike J. Bemelman
Journal: Kidney International (2010)
Development of a Ventilatory Classification System in Patients With Heart Failure
Authors: Ross Arena, Jonathan Myers, Joshua Abella, Mary Ann Peberdy, Daniel Bensimhon, Paul Chase, Marco Guazzi
Journal: Circulation (2007)

Ventilatory efficiency, commonly assessed by the minute ventilation (VE)-carbon dioxide production (VCO2) slope, is a powerful prognostic marker in the heart failure population. The purpose of the present study is to refine the prognostic power of the VE/VCO2 slope by developing a ventilatory class system that correlates VE/VCO2 cut points to cardiac-related events.Four hundred forty-eight subjects diagnosed with heart failure were included in this analysis. The VE/VCO2 slope was determined via cardiopulmonary exercise testing. Subjects were tracked for major cardiac events (mortality, transplantation, or left ventricular assist device implantation) for 2 years after cardiopulmonary exercise testing. There were 81 cardiac-related events (64 deaths, 10 heart transplants, and 7 left ventricular assist device implantations) during the 2-year tracking period. Receiver operating characteristic curve analysis revealed the overall VE/VCO2 slope classification scheme was significant (area under the curve: 0.78 [95% CI, 0.73 to 0.83], P<0.001). On the basis of test sensitivity and specificity, the following ventilatory class system was developed: (1) ventilatory class (VC) I: < or = 29; (2) VC II: 30.0 to 35.9; (3) VC III: 36.0 to 44.9; and (4) VC IV: > or = 45.0. The numbers of subjects in VCs I through IV were 144, 149, 112, and 43, respectively. Kaplan-Meier analysis revealed event-free survival for subjects in VC I, II, III, and IV was 97.2%, 85.2%, 72.3%, and 44.2%, respectively (log-rank 86.8; P<0.001).A multiple-level classificatory system based on exercise VE/VCO2 slope stratifies the burden of risk for the entire spectrum of heart failure severity. Application of this classification is therefore proposed to improve clinical decision making in heart failure.
Concerns are raised over professors detained in Egypt since military coup
Authors: A. O'Dowd
Journal: BMJ (2013)

Fifty nine professors from various backgrounds including medicine have been arrested and detained in Egypt since the military coup this year, it has emerged.

Local newspapers in Egypt, social media networks, and several doctors contacted by the BMJ said that the professors have been detained since the military coup in July, mostly for speaking out against the current regime that deposed former president Mohamed Morsi.

Among the people arrested recently are Mustafa Issa, professor of gynaecology and obstetrics at the Faculty of Medicine, Minia University, Egypt.

Issa, a fellow of the Royal College of Obstetrics and Gynaecology, is accused of inciting violence, murder, and arson of churches in Minia during recent conflicts in the Minia governate that followed the coup in July.

Other academics who have been arrested include Yahia El-Kashef, a professor in ear, nose, …
Influence of Catheter Tip Position on Pulmonary Wedge Pressures
Authors: A. L. Loomis Bell, William F. Haynes, Seiichi Shimomura, Donald P. Dallas
Journal: Circulation Research (1962)

Pulmonary artery wedge pressures and wedge pulmonary arteriograms were obtained in 68 patients with either mitral stenosis, congenital heart disease, or no demonstrable heart disease. The arteriogram defines five catheter tip positions in the wedged artery. Tip positions unfavorable for left atrial pressure transmission occurred in 20 of the 68 trials and accounted for 19 of the 31 unsatisfactory tracings. Favorable tip positions were found in 48 instances and resulted in 36 phasic tracings. Unsatisfactory tracings in patients with pulmonary hypertension and congenital heart disease are shown to result primarily from unfavorable catheter tip positions. In these patients structural changes in the larger pulmonary arteries may prevent proper wedging. Increased left atrial pressure assures transmission of a cyclic left atrial pulse to a properly impacted catheter regardless of the degree of associated pulmonary hypertension. It is concluded that the fortuitous position assumed by the catheter tip in the wedged artery and the level of the left atrial pressure are factors of major importance in the satisfactory recording of the left atrial pulse curve by the wedged catheter.
Doctors' suspensions and exclusions rise but are processed faster
Authors: A. O'Dowd
Journal: BMJ (2011)

The number of doctors and dentists either suspended or excluded from work in the NHS has risen steadily in the past five years, but cases are being dealt with faster, says the National Patient Safety Agency.

A report by the agency’s national clinical assessment service (NCAS) on suspensions (which apply to GPs and dentists in primary care) and exclusions (the term used for hospital and community doctors and dentists) found that collectively 1134 cases were opened and 1131 closed between 2005-6 and 2010-11 in England.

The NCAS said that doctors were being suspended or excluded for shorter periods, which was helping to save the NHS millions of pounds …
A Controlled Trial of a Critical Pathway for Treatment of Community-Acquired Pneumonia
Authors: Thomas J. Marrie
Journal: JAMA (2000)

ContextLarge variations exist among hospitals in the use of treatment resources for community-acquired pneumonia (CAP). Lack of a common approach to the diagnosis and treatment of CAP has been cited as an explanation for these variations.ObjectiveTo determine if use of a critical pathway improves the efficiency of treatment for CAP without compromising the well-being of patients.DesignMulticenter controlled clinical trial with cluster randomization and up to 6 weeks of follow-up.SettingNineteen teaching and community hospitals in Canada.PatientsA total of 1743 patients with CAP presenting to the emergency department at 1 of the participating institutions between January 1 and July 31, 1998.InterventionHospitals were assigned to continue conventional management (n = 10) or implement the critical pathway (n = 9), which consisted of a clinical prediction rule to guide the admission decision, levofloxacin therapy, and practice guidelines.Main Outcome MeasuresEffectiveness of the critical pathway, as measured by health-related quality of life on the Short-Form 36 Physical Component Summary (SF-36 PCS) scale at 6 weeks; and resource utilization, as measured by the number of bed days per patient managed (BDPM).ResultsQuality of life and the occurrence of complications, readmission, and mortality were not different for the 2 strategies; the 1-sided 95% confidence limit of the between-group difference in the SF-36 PCS change score was 2.4 points, which was within a predefined 3-point boundary for equivalence. Pathway use was associated with a 1.7-day reduction in BDPM (4.4 vs 6.1 days; P = .04) and an 18% decrease in the admission of low-risk patients (31% vs 49%; P = .01). Although inpatients at critical pathway hospitals had more severe disease, they required 1.7 fewer days of intravenous therapy (4.6 vs 6.3 days; P = .01) and were more likely to receive treatment with a single class of antibiotic (64% vs 27%; P&lt;.001).ConclusionIn this study, implementation of a critical pathway reduced the use of institutional resources without causing adverse effects on the well-being of patients.
Thoracic manifestations of Behcet's syndrome.
Authors: A G Decroix
Journal: Thorax (1969)

Proceedings of the Thoracic Society 0.8 mg./kg., was given.Of the 10 patients treated, four were completely relieved, five were partially relieved, and only one showed no response.The speed of response varied from one to 10 days.Symptomatic improvement was notable.The duration of relief varied from four weeks to eight months.Recurrence of superior vena caval obstruction needing further treatment was seen in two of these patients, and another patient died of recurrent superior vena caval obstruction.It is felt that the results of this small series warrant further consideration of this readily available method of treatment as an alternative to radiotherapy.
Heterotopic gastric mucosa together with intestinal metaplasia and moderate dysplasia in the gall bladder: report of two clinically unusual cases with literature review
Authors: N Xeropotamos, A S Skopelitou, Ch Batsis, A M Kappas
Journal: Gut (2001)

We report the clinicopathological findings of two patients with ectopic gastric mucosa within the gall ladder. The first patient, a 78 year old man, was asymptomatic. He was admitted to hospital for a colon adenocarcinoma. Intraoperatively, a firm nodule was palpable in the gall bladder. Histological examination of the resected specimen revealed a body type gastric mucosa in the submucosa, adjacent to which were extensive pyloric gland and intestinal metaplasia with mild to moderate dysplasia. The remaining gall bladder mucosa demonstrated changes of chronic cholecystitis. The second patient was a 62 year old woman with symptoms of chronic cholecystitis. The preoperative diagnosis was consistent with this diagnosis with a “polyp” at the junction of the neck and cystic duct. Cholecystectomy was performed and the histological examination of the resected specimen showed that the “polyp” consisted of heterotopic gastric mucosa with glands of body and fundus type. In the remaining mucosa, chronic cholecystitis was evident. To the best of our knowledge, this is the first report of a clinicopathological presentation of heterotopic gastric mucosa, pyloric gland type, and intestinal metaplasia with dysplastic changes in the gall bladder. As heterotopic tissue may promote carcinogenesis of the gall bladder, close attention should be paid to any occurrence of such lesions in this anatomical region.
VISUAL HALLUCINATIONS WITH IMIPRAMINE
Authors: DONALD F. KLEIN
Journal: American Journal of Psychiatry (1965)

The occasional occurrence of imipramine-induced visual hallucinations resembling those produced by hallucinogenic agents is documented. The phenomenon is dosage dependent and easily managed by reduction of dosage level when recognized. Delirious confusion is not a necessary part of this syndrome. This phenomenon's relationships to age, diagnosis, and psychopathological features are discussed and contrasted with visual hallucinations of schizophrenia. The possibility of a common organic CNS predisposition to depersonalization, derealization, and visual hallucinosis is indicated.
Long-term associations of outdoor air pollution with mortality in Great Britain
Authors: P. Elliott, G. Shaddick, J. C Wakefield, C. d. Hoogh, D. J Briggs
Journal: Thorax (2007)

<h3>Background:</h3> Recent studies have indicated long-term effects on mortality of particulate and sulphur dioxide (SO<sub>2</sub>) pollution, but uncertainties remain over the size of any effects, potential latency and generalisability. <h3>Methods:</h3> A small area study was performed across electoral wards in Great Britain of mean annual black smoke (BS) and SO<sub>2</sub> concentrations (from 1966) and subsequent all-cause and cause-specific mortality using random effect models within a Bayesian framework adjusted for social deprivation and urban/rural classification. Different latencies and changes in associations over time were assessed. <h3>Results:</h3> Significant associations were found between BS and SO<sub>2</sub> concentrations and mortality. The effects were stronger for respiratory illness than other causes of mortality for the most recent exposure periods (shorter latency times) and most recent mortality period (lower pollutant concentrations). In pooled analysis across four sequential 4 year mortality periods (1982–98), adjusted excess relative risk for respiratory mortality was 3.6% (95% CI 2.6% to 4.5%) per 10 μg/m<sup>3</sup> BS and 13.2% (95% CI 11.5% to 14.9%) per 10 ppb SO<sub>2</sub>, and in the most recent period (1994–8) it was 19.3% (95% CI 5.1% to 35.7%) and 21.7% (95% CI 2.9% to 38.5%), respectively. <h3>Conclusions:</h3> These findings add to the evidence that air pollution has long-term effects on mortality and point to continuing public health risks even at the relatively lower levels of BS and SO<sub>2</sub> that now occur. They therefore have importance for policies on public health protection through regulation and control of air pollution.
FXR-mediated regulation of eNOS expression in vascular endothelial cells
Authors: Jiang Li, Annette Wilson, Ramalinga Kuruba, Qiuhong Zhang, Xiang Gao, Fengtian He, Li-Ming Zhang, Bruce R. Pitt, Wen Xie, Song Li
Journal: Cardiovascular Research (2007)

The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is highly expressed in liver, kidney, adrenals, and intestine. FXR was previously proposed to play an important role in the pathogenesis of cardiovascular diseases via regulating the metabolism and transport of cholesterol. We have recently shown that FXR is also expressed in rat pulmonary vascular endothelial cells (EC) and that activation of FXR leads to inhibition of endothelin-1 expression. In the present study, we examine whether activation of FXR also affects the expression of endothelial nitric oxide synthase (eNOS) in rat, bovine, and sheep vascular EC. Treatment of vascular EC with a FXR ligand resulted in upregulation of expression of eNOS mRNA and protein and an increased production of nitrite/nitrate. FXR appears to induce eNOS expression at a transcriptional level because (1) upregulation of eNOS mRNA expression was abolished by the treatment of a transcription inhibitor, actinomycin D; and (2) eNOS promoter activity was significantly increased by pharmacological or genetic activation of FXR. Functional analysis of rat eNOS promoter identified an imperfect inverted repeat DNA motif, IR2 (−628AGCTCAgtGGACCT-641), as a likely FXR-responsive element that is involved in eNOS regulation. These results support the notion that vascular FXR may serve as a novel molecular target for manipulating the expression of eNOS for the treatment of vascular diseases.
Early Detection of Fabry Cardiomyopathy by Tissue Doppler Imaging
Authors: Maurizio Pieroni, Cristina Chimenti, Roberta Ricci, Patrizio Sale, Matteo Antonio Russo, Andrea Frustaci
Journal: Circulation (2003)

Fabry cardiomyopathy is diagnosed by detection of left ventricular hypertrophy (LVH) in patients with alpha-Galactosidase A deficiency. Conventional noninvasive tools are unable to provide a preclinical diagnosis allowing prompt institution of enzymatic therapy.We studied three groups of patients: 10 patients with causal mutations for Fabry disease and LVH, 10 mutation-positive patients without LV, and 10 healthy relatives without causal mutations and no LVH. All patients with LVH and 6 patients with Fabry disease without LVH with complex repetitive ventricular arrhythmias underwent biventricular endomyocardial biopsy to assess cardiac involvement. In all patients 2-dimensional echocardiography with tissue Doppler analysis in the pulsed Doppler mode was performed: systolic (Sa), early diastolic (Ea), and late diastolic (Aa) velocities were measured, and the Ea/Aa ratio and the dimensionless parameter E/Ea were computed at both corners of the mitral annulus. Histology and electron microscopy studies showed glycosphingolipid deposits in all cases. All mutation-positive patients had significant reduction of Sa, Ea, and Aa velocities at both corners of the mitral annulus compared with normal control subjects. Ea/Aa ratio was significantly lower and E/Ea ratio significantly higher in mutation-positive patients than in control subjects. Patients with LVH showed significantly lower contraction and relaxation tissue Doppler velocities, lower Ea/Aa ratio, and higher E/Ea ratio in comparison with mutation-positive patients with no LVH.Fabry cardiomyopathy is characterized by reduced myocardial contraction and relaxation tissue Doppler velocities, detectable even before development of LVH. Tissue Doppler imaging can provide a preclinical diagnosis of Fabry cardiomyopathy, allowing early institution of enzyme replacement therapy.
Enhanced Salience and Emotion Recognition in Autism: A PET Study
Authors: Geoffrey B.C. Hall, Henry Szechtman, Claude Nahmias
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: This study examined neural activation of facial stimuli in autism when the salience of emotional cues was increased by prosodic information. METHOD: Regional cerebral blood flow (rCBF) was measured while eight high-functioning men with autism and eight men without autism performed an emotion-recognition task in which facial emotion stimuli were matched with prosodic voices and a baseline gender-recognition task. RESULTS: Emotion processing in autistic subjects, compared to that in comparison subjects, resulted in lower rCBF in the inferior frontal and fusiform areas and higher rCBF in the right anterior temporal pole, the anterior cingulate, and the thalamus. CONCLUSIONS: Even with the enhanced emotional salience of facial stimuli, adults with autism showed lower activity in the fusiform cortex and differed from the comparison subjects in activation of other brain regions. The authors suggested that the recognition of emotion by adults with autism is achieved through recruitment of brain regions concerned with allocation of attention, sensory gating, the referencing of perceptual knowledge, and categorization.
Premedication with zolpidem may reduce poor quality polysomnography
Authors: P Bhatia
Journal: Thorax (2005)

▴ Letteri CJ, Eliasson AH, Andrada T, et al . Does zolpidem enhance the yield of polysomnography? J Clin Sleep Med2005;1:129–31

[OpenUrl][1][PubMed][2]



The increasing awareness of sleep disordered breathing has resulted in an increased demand for polysomnography (PSG). A number of factors may lead to poor quality studies requiring repeat studies; these factors can prolong waiting times.

Zolpidem is a non-benzodiazepine sedative which has been shown to decrease sleep latency and increase sleep efficiency with minimal side effects on …

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