tbuckley/cabot-search huggingface dataset:
Lipoxin A4 modulates transmigration of human neutrophils across intestinal epithelial monolayers.
Authors: S P Colgan, C N Serhan, C A Parkos, C Delp-Archer, J L Madara
Journal: Journal of Clinical Investigation (1993)

Neutrophil (PMN) migration across intestinal epithelial barriers, such as occurs in many disease states, results in modifications in epithelial barrier. Here, we investigated the impact of lipoxin A4 (LXA4), an eicosanoid with counterregulatory inflammatory roles, on PMN migration across cultured monolayers of the human intestinal epithelial cell line T84. Transepithelial migration of PMN was assessed in the apical-to-basolateral direction and in the basolateral-to-apical direction. In the apical-to-basolateral direction, preexposure of PMN to LXA4 (10 nM, 15 min) stimulated an 87 +/- 5% increase in transepithelial migration of PMN as determined by a PMN myeloperoxidase assay. The LXA4-elicited effect on transmigration was present throughout the 2-h assay period and was not secondary to LXA4 effects on epithelial monolayer integrity as judged by measurement of transepithelial resistance. PMN migration in the basolateral-to-apical direction was modulated by LXA4 with a comparable time- and concentration-dependence to that in the apical-to-basolateral direction. However, qualitative differences in how LXA4 modulates transmigration in the two opposing directions were observed. In the basolateral-to-apical direction, preexposure of PMN to LXA4 (10 nM, 15 min) diminished PMN transepithelial migration by 33 +/- 4%. Structure-function studies revealed that LXA4 and 11-trans-LXA4 (50% of LXA4 effect), but not LXB4, inhibited basolateral-to-apical PMN transmigration. The action of LXA4 was not sensitive to inhibitors of cyclooxygenase or specific leukotriene biosynthesis, but was sensitive to staurosporine, a protein kinase C inhibitor. These results suggest that migration of PMN across epithelia in the physiological direction may be qualitatively different following PMN exposure to eicosanoids. We propose that such retention of PMN at this specific anatomic location may serve an important role in mucosal defense.
Cultured Skin Cells, Artificial Dermis Join in Race Against Time to Cover Burn Wound
Authors: Teri Randall
Journal: JAMA (1991)

THE KEY to survival for today's burn patients depends on the expedient closure of the wound after excision of the burned tissue. Yet this objective has become more difficult to accomplish now that many patients with burns that cover 80% or more of their bodies are surviving. With so much tissue burned, less healthy skin is available for autografts, and donor sites take longer to heal with each successive harvest. "We've pushed back survival as far as we can with infection control, nutrition, techniques of excision, and so on. But unless we close the wound, the patient will still die," says William F. McManus, MD, a US Army colonel, and chief, Clinical Division, US Army Institute for Surgical Research (USAISR), Fort Sam Houston, San Antonio, Tex. Typically, the dead, burned tissue is surgically excised around the fourth day after the injury. Yet the hypermetabolism, immunosuppression, and other physiological changes caused
286. Therapeutic Approach Using External Radiation and Suicide Gene Therapy Transduced by Chimeric Adenovirus Vector for Bladder Cancer
Authors: Kazumasa Matsumoto, Norihiko Okuno, Bin S. Teh, Christian T.F. Freund, Julie X. Zhu, Maria T. Vlachaki, Alan R. Davis, Brian E. Butler, Seth P. Lerner
Journal: Molecular Therapy (2005)

Background: Radiation therapy is an established therapy for advanced bladder cancer. Interestingly, radiation therapy has been shown to improve both transduction efficiency and transgene expression. However, alteration of the coxsackie and adenovirus receptor (CAR) poses a barrier to adenovirus-mediated gene therapy, particularly in higher grade and stage bladder cancers with potential for metastasis. We have previously shown the efficacy of a CAR-independent Ad vector (Ad5/F35) expressing HSV-tk with GCV in CAR-negative and CAR-positive human bladder cancer models. In the present study, we sought to determine whether independently of CAR status, combination radiogene therapy is more effective than gene therapy alone in bladder cancer and minimizes treatment-related toxicity.
Some Observations on the Natural Behavior of Cancer in Man
Authors: J. Englebert Dunphy
Journal: New England Journal of Medicine (1950)

IT IS generally accepted by surgeons that cancer grows in a steady and irrevocable manner, the rate of which is a function of the particular tumor and bears a fairly close relation to the histologic appearance of the lesion. Not only are apparent arrests or regressions of tumors usually attributed to faulty observations or recent therapy but also little or no consideration is given to the possibility of a natural resistance to cancer. The thesis of this paper is that malignant neoplasms undergo periods of spontaneous arrest or regression alternating with periods of growth and that this phenomenon is a . . .
Effects of acute ischemia in the dog on myocardial blood flow, beta receptors, and adenylate cyclase activity with and without chronic beta blockade.
Authors: J S Karliner, M B Stevens, N Honbo, J I Hoffman
Journal: Journal of Clinical Investigation (1989)

We ligated the left anterior descending coronary artery for 1 or 2 h in 31 purebred beagles. We did not detect any changes in beta-adrenergic receptor density or affinity when normal and ischemic zones were compared, either in the subendocardium or in the subepicardium. In the ischemic zones, there was a significant decline in all measures of adenylate cyclase activity, including activity mediated by the beta-adrenergic receptor. By contrast, after chronic beta-adrenergic blockade (1.5 mg/kg propranolol i.v. twice daily for 7 d), there was an increase in adenylate cyclase activity stimulated by (-)-isoproterenol relative to adenylate cyclase activity stimulated by guanyl-5'imidodiphosphate (GppNHp) in both normal and ischemic tissue, suggesting that one effect of chronic beta blockade may be to enhance coupling between the stimulatory guanine nucleotide regulatory protein (Gs) and the beta-adrenergic receptor, despite a reduction in the number or function of Gs units. Chronic beta blockade also led to up regulation of beta-adrenergic receptor density in subepicardial regions. After 20 min of reperfusion following 2 h of ischemia, adenylate cyclase activity tended to return to control levels, particularly in the subepicardium, where (-)-isoproterenol-stimulated adenylate cyclase activity was not different from normal myocardium. We conclude that chronic beta-adrenergic blockade may have beneficial effects during prolonged episodes of myocardial ischemia by preserving signal transduction mediated by the beta-adrenergic receptor.
Urokinase and type I plasminogen activator inhibitor production by normal human hepatocytes: Modulation by inflammatory agents
Authors: Nathalie Busso, Edwige Nicodeme, Christophe Chesne, André Guillouzo, Dominique Belin, François Hyafil
Journal: Hepatology (1994)

ABSTRACT We examined the effects of inflammatory cytokines (interleukin–1β, tumor necrosis factor–α and transforming growth factor–β) on the plasminogen activator system (urokinase, tissue–type plasminogen activator, type 1 plasminogen activator inhibitor) in primary cultures of human hepatocytes. We show that interleuklin–1β and tumor necrosis factor–α increase urokinase–type plasminogen activator production, reinforcing the concept that increased urokinase production is associated with inflammatory processes. By contrast, the same agents (i.e., interleukin–1β and tumor necrosis factor–α) do not stimulate plasminogen activator inhibitor type 1 production. This latter observation rules out hepatocytes as a major cellular source of plasmatic plasminogen activator inhibitor type 1 during acute–phase-related responses. Among the inflammatory agents used, transforming growth factor–β was found to be the most effective modulator of both urokinase–type plasminogen activator and plasminogen activator inhibitor type 1, inducing severalfold increases of activity of urokinase–type plasminogen activator, antigen and the corresponding mRNA and increasing plasminogen activator inhibitor type 1 antigen and mRNA levels. Urokinase–type plasminogen activator and plasminogen activator inhibitor type 1 modulation by transforming growth factor–β may play a critical role in hepatic pathophysiology. (Hepatology 1994;20:186-190.)
Bad medicine: monitoring patients' drugs
Authors: D. Spence
Journal: BMJ (2013)

Once when I worked on a long stay ward for elderly people the consultant demanded that blood be taken every week from all patients for monitoring tests. “Why?” I asked. Eyes narrowed. “Because I say so.” So I did as I was told.

But evidence based medicine has encouraged questioning, and evidence has become a weapon to wield against deference and the dogma of the acerbic expert. Today, reviewing patients and monitoring drugs is an ever increasing part of our medical work. But are these reviews actually necessary, and at what interval?

Regular reviews are ingrained in …
Quantification of subclonal distributions of recurrent genomic aberrations in paired pre-treatment and relapse samples from patients with B-cell chronic lymphocytic leukemia
Authors: S J L Knight, C Yau, R Clifford, A T Timbs, E Sadighi Akha, H M Dréau, A Burns, C Ciria, D G Oscier, A R Pettitt, S Dutton, C C Holmes, J Taylor, J-B Cazier, A Schuh
Journal: Leukemia (2012)

Genome-wide array approaches and sequencing analyses are powerful tools for identifying genetic aberrations in cancers, including leukemias and lymphomas. However, the clinical and biological significance of such aberrations and their subclonal distribution are poorly understood. Here, we present the first genome-wide array based study of pre-treatment and relapse samples from patients with B-cell chronic lymphocytic leukemia (B-CLL) that uses the computational statistical tool OncoSNP. We show that quantification of the proportion of copy number alterations (CNAs) and copy neutral loss of heterozygosity regions (cnLOHs) in each sample is feasible. Furthermore, we (i) reveal complex changes in the subclonal architecture of paired samples at relapse compared with pre-treatment, (ii) provide evidence supporting an association between increased genomic complexity and poor clinical outcome (iii) report previously undefined, recurrent CNA/cnLOH regions that expand or newly occur at relapse and therefore might harbor candidate driver genes of relapse and/or chemotherapy resistance. Our findings are likely to impact on future therapeutic strategies aimed towards selecting effective and individually tailored targeted therapies.
FDA warns against commercial prenatal ultrasound videos
Authors: Janice Hopkins Tanne
Journal: BMJ (2004)

Prenatal ultrasound videos called “keepsake videos” and taken by commercial studios may affect the fetus, warns the US Food and Drug Administration. The administration shut down such studios 10 years ago and is again considering regulatory action. Ultrasound is a form of energy and can't be considered harmless, even at low levels, it says.

The studios have been springing up in shopping centres in cities and towns across the United States. Typically they use the latest high powered ultrasound equipment, which can cost up to $100 000 (£54 000; €81 000), to produce videos of the …
The fetal prognosis in pemphigoid gestationis (herpes gestationis)
Authors: R.C. HOLMES, M.M. BLACK
Journal: British Journal of Dermatology (1984)

We have studied the infants in fifty pregancies affected by pemphigoid gestationis (herpes gestationis). There was a significant increase in the frequency of infants that were 'small for dates'. As such infants have a raised mortality and morbidity it follows that in pemphigoid gestationis the fetal prognosis is impaired. In view of this it is essential that patients with pemphigoid gestationis are delivered in maternity units which have facilities for intensive care of the newborn. There has long been uncertainty over the fetal prognosis in pemphigoid gestationis (PG) (formerly called herpes gestationis) and this has not been dispelled by two recent studies. A literature review of immunofluorescence positive cases indicated that the risk to the fetus was substantial (Lawley, Stingl & Katz, 1978) while a further report found no evidence of increased morbidity or mortality (Shornick et al., 1983). The inconsitency of these studies may stem from the fact that their conclusion were based solely on the fetal outcome which could have varied with the standard of obstetric and perinatal care. A fundamental method of assessing fetal risk is to simply measure the infant weight and compare it with the weight expected for the gestation. This information has not been recorded in previous studies of PG. In our patients documentation of the infants'weights and gestations and calculation of the incidence of 'small for dates'infants has enabled us to clearly define the fetal risk in PG.
Controversy in medicine: Access to employee health records
Authors: John Elliott
Journal: JAMA (1979)

Whatever, in connection with my professional practice, or not in connection with it, I may see or hear in the lives of men which ought not to be spoken abroad, I will not divulge, as reckoning that all such should be kept secret.—The Oath of Hippocrates  The complex and often bitter debate over who shall have access to employee medical records will reach a denouement within the next several months as the Occupational Safety and Health Administration (OSHA) ponders the final details of a new set of regulations in this area.  The proposed OSHA regulations, while pertaining only to employee medical records, may well mark the beginning of a tumultuous upheaval in the traditional handling of all medical records.  In addition, several signs indicate that Congress is primed to tackle the records confidentiality issue in the present session. Senate bill 3450, along with House of Representatives bill 13994, both
Good medical practice
Authors: J. Snape, B. Elliott
Journal: BMJ (2011)

<h3>Objectives</h3> (1) To identify operational issues encountered by study participants in using the ‘Care for Stroke’ intervention; (2) to evaluate the feasibility and acceptability of the intervention. <h3>Design</h3> Mixed-methods research design. <h3>Setting</h3> Participant9s home. Participants were selected from a tertiary hospital in Chennai, South India. <h3>Participants</h3> Sixty stroke survivors treated and discharged from the hospital, and their caregivers. <h3>Intervention</h3> ‘Care for Stroke’ is a smartphone-enabled, educational intervention for management of physical disabilities following stroke. It is delivered through a web-based, smartphone-enabled application. It includes inputs from stroke rehabilitation experts in a digitised format. <h3>Methods</h3> Evaluation of the intervention was completed in two phases. In the first phase, the preliminary intervention was field-tested with 30 stroke survivors for 2 weeks. In the second phase, the finalised intervention was provided to a further 30 stroke survivors to be used in their homes with support from their carers for 4 weeks. <h3>Primary and secondary outcome measures</h3> Primary outcomes: (1) operational difficulties in using the intervention; (2) feasibility and acceptability of the intervention in an Indian setting. Disability and dependency were assessed as secondary outcomes. <h3>Results</h3> Field-testing identified operational difficulties related to connectivity, video-streaming, picture clarity, quality of videos, and functionality of the application. The intervention was reviewed, revised and finalised before pilot-testing. Findings from the pilot-testing showed that the ‘Care for Stroke’ intervention was feasible and acceptable. Over 90% (n=27) of the study participants felt that the intervention was relevant, comprehensible and useful. Over 96% (n=29) of the stroke survivors and all the caregivers (100%, n=30) rated the intervention as excellent and very useful. These findings were supported by qualitative interviews. <h3>Conclusions</h3> Evaluation indicated that the ‘Care for Stroke’ intervention was feasible and acceptable in an Indian context. An assessment of effectiveness is now warranted.
Noninvasive Diagnosis of Deep Venous Thrombosis
Authors: Clive Kearon
Journal: Annals of Internal Medicine (1998)

To review noninvasive methods for diagnosis of first and recurrent deep venous thrombosis and provide evidence-based recommendations for the diagnosis of deep venous thrombosis in symptomatic, asymptomatic, and pregnant patients.Accuracy (comparison with contrast venography) and management (safety of withholding anticoagulants when results were normal) studies that evaluated tests for diagnosis of deep venous thrombosis were identified from a MEDLINE search, personal files, and bibliographies of reviews and original studies.Prospective cohort studies (accuracy and management studies) and randomized comparisons (management studies) that satisfied predefined methodologic criteria were included.Sensitivity, specificity, and positive and negative predictive values were determined for accuracy studies. Rates of venous thromboembolism during long-term follow-up of patients with normal results were determined for management studies.Data from individual studies were combined under a random-effects model. The accuracy of noninvasive tests was compared, with emphasis on within-study comparisons. Recommendations for diagnosis of deep venous thrombosis were developed by a multidisciplinary group and graded according to the strength of the supporting evidence. Venous ultrasonography is the most accurate noninvasive test for the diagnosis of a first symptomatic proximal deep venous thrombosis. However, neither ultrasonography nor impedance plethysmography is accurate in asymptomatic postoperative patients. Venous ultrasonography is less accurate for symptomatic isolated distal (calf) deep venous thrombosis than for proximal deep venous thrombosis, and the clinical utility of venous ultrasonography of the distal veins is uncertain. Withholding anticoagulant therapy in symptomatic patients with suspected deep venous thrombosis who have normal results on serial venous ultrasonography or impedance plethysmography is safe. Diagnosis of recurrent deep venous thrombosis requires evidence of new thrombus formation, such as a new noncompressible venous segment detected by venous ultrasonography, conversion of a normal result on impedance plethysmography to abnormal, or presence of an intraluminal filling defect on venography. Suspected deep venous thrombosis in pregnant patients can usually be managed with serial venous ultrasonography or impedance plethysmography. In symptomatic patients with a suspected first episode of deep venous thrombosis, clinical assessment and D-dimer testing are complementary to testing with venous ultrasonography and impedance plethysmography.Patients with suspected deep venous thrombosis can usually be managed with noninvasive testing. However, if the results of this testing are nondiagnostic or are discordant with the clinical assessment, venography should be considered.
THE USE OF SILVER ARSPHENAMIN IN THE TREATMENT OF WASSERMANN-FAST SYPHILIS
Authors: Irwin C. Sutton
Journal: JAMA (1923)

Many articles regarding the efficiency of silver arsphenamin have appeared in the literature since Kolle,<sup>1</sup>in 1918, published the first of his series of reports. This much is established: it is an efficient spirocheticide; it is reasonably free from reactions, and it can be as conveniently administered as any other arsenical preparation. The twenty-one cases reported were Wassermann fast. The patients, previous to the administration of the silver preparation, had had from four to thirty-four injections of arsphenamin and from thirteen to sixty-seven intramuscular injections of an insoluble mercury salt. The presence of a persistently positive Wassermann reaction in cases of intensive treatment is conceivably due to the continued activity of nests or foci of spirochetes resistant to medication. These foci are usually present in the cardiovascular and nervous systems. Detailed reexamination of these patients revealed evidence of activity that was unsuspected before treatment was instituted. These data are
Randomized Controlled Comparison of Cognitive Behavior Therapy with Rogerian Supportive Therapy in Chronic Post-Traumatic Stress Disorder: A 2-Year Follow-Up
Authors: Jean Cottraux, Ivan Note, Sai Nan Yao, Chantal de Mey-Guillard, Françoise Bonasse, Diane Djamoussian, Evelyne Mollard, Brigitte Note, Yaohua Chen
Journal: Psychotherapy and Psychosomatics (2008)

&lt;i&gt;Background:&lt;/i&gt; To date, there have been no studies comparing cognitive behavior therapy (CBT) with Rogerian therapy in post-traumatic stress disorder. &lt;i&gt;Method:&lt;/i&gt; Sixty outpatients with DSM-IV chronic post-traumatic stress disorder were randomized into two groups for 16 weekly individual sessions of CBT or Rogerian supportive therapy (ST) at two centers. No medication was prescribed. Measures included the Post-Traumatic Stress Disorder Checklist Scale (PCLS), the Hamilton Anxiety Scale, Beck Depression Inventory, and Quality of Life. The general criterion of improvement (GCI) was a score of less than 44 on the PCLS. &lt;i&gt;Results:&lt;/i&gt; Forty-two patients were evaluated at post-test, 38 at week 52 and 25 at week 104. At post-test, the rate of patients leaving the trial due to worsening or lack of effectiveness was significantly higher in the ST group (p = 0.004). At this point, no between-group difference was found on the GCI and any of the rating scales. Intent-to-treat analysis found no difference for the GCI, but patients in the CBT group showed greater improvement on the PCLS and Hamilton Anxiety Scale. Naturalistic follow-up showed sustained improvement without between-group differences at weeks 52 and 104. &lt;i&gt;Conclusions:&lt;/i&gt; CBT retained significantly more patients in treatment than ST, but its effects were equivalent to those of ST in the completers. CBT was better in the dimensional intent-to-treat analysis at post-test.
A Novel Alveolar Type I Cell–Specific Biochemical Marker of Human Acute Lung Injury
Authors: VALERIE NEWMAN, ROBERT F. GONZALEZ, MICHAEL A. MATTHAY, LELAND G. DOBBS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Currently there is no recognized biochemical or molecular marker for human parenchymal lung injury analogous to markers for acute myocardial injury. Injury to the alveolar epithelial barrier is of central importance in the pathogenesis of and recovery from acute lung injury. In animal models, an alveolar type I cell-specific protein, RTI(40), has been shown to be an accurate marker of alveolar epithelial damage. We now report that HTI(56), a novel apical plasma membrane protein specific to the human type I cell, is a biochemical marker for lung injury. Using a sensitive, quantitative, light-based ELISA, we measured HTI(56) in pulmonary edema fluid from 15 patients with a clinical diagnosis of acute lung injury and 12 control patients with hydrostatic (cardiogenic) pulmonary edema. HTI(56) was also measured in plasma from these two groups and from 11 normal volunteers. The amount of HTI(56) was 4. 3-fold higher (p < 0.0001) in alveolar edema fluid and 1.4-fold higher (p < 0.05) in plasma from the patients with acute lung injury, compared with patients with hydrostatic pulmonary edema. To our knowledge, this study is the first to utilize a specific marker of alveolar epithelial damage in human disease and demonstrates the feasibility of using a blood test to detect lung parenchymal damage.