tbuckley/cabot-search huggingface dataset:
Diffuse inflammatory lesions in patients treated with interferon alfa and ribavirin for hepatitis C: a series of 20 patients
Authors: O. Dereure, N. Raison-Peyron, D. Larrey, F. Blanc, J-J. Guilhou
Journal: British Journal of Dermatology (2002)

Cutaneous side-effects of treatment with interferon alfa or interferon alfa plus ribavirin in patients with hepatitis C have already been reported but they are mostly local with inflammation and, much less frequently, necrosis at the injection points. By contrast, very few data are available with regard to distant skin reactions, particularly inflammatory lesions on other parts of the body.To assess the clinical and histological pattern of inflammatory skin lesions outside the injection points in patients treated with interferon alfa and ribavirin for chronic hepatitis C.Twenty patients attending a University Hospital in Southern France (secondary referral centre) were evaluated regard to clinical history, type and localization of lesions, progression and histology. Skin testing was performed in some patients and the relevance of the results was evaluated.Eczema-like skin lesions were mainly distributed on the extremities, sometimes associated with photosensitivity. They usually occurred between 2 and 4 months of treatment. Histology was nonspecific, with a dermal, mainly perivascular, mononuclear infiltrate. Skin testing was poorly informative and was not predictive of relapse. Treatment had to be interrupted in half the patients, of whom two of three relapsed on resuming therapy.The incidence of inflammatory skin lesions at a distance from injection sites in patients treated with interferon alfa and ribavirin for chronic hepatitis C is currently unknown, but this adverse event must be taken into consideration as it may lead to the transient or definitive interruption of treatment.
Reduction of Bacterial Resistance with Inhaled Antibiotics in the Intensive Care Unit
Authors: Lucy B. Palmer, Gerald C. Smaldone
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Multidrug-resistant organisms (MDRO) are the dominant airway pathogens in the intensive care unit (ICU) and present a major treatment challenge to intensivists. Aerosolized antibiotics (AA) result in airway concentrations of drug 100-fold greater than the minimal inhibitory concentration of most bacteria including MDRO. These levels, without systemic toxicity, may eradicate MDRO and reduce the pressure for selection of new resistant organisms.To determine if AA effectively eradicate MDRO in the intubated patient without promoting new resistance.In a double-blind placebo-controlled study, critically ill intubated patients were randomized if they exhibited signs of respiratory infection (purulent secretions and Clinical Pulmonary Infection Score ≥6). Using a well-characterized aerosol delivery system, AA or saline placebo was given for 14 days or until extubation. The responsible clinician determined administration of systemic antibiotics for ventilator-associated pneumonia and any other infection.AA eradicated 26 of 27 organisms present at randomization compared with 2 of 23 organisms with placebo (P < 0.0001). AA eradicated the original resistant organism on culture and Gram stain at end of treatment in 14 out of 16 patients compared with 1 of 11 for placebo (P < 0.001). New drug resistance to AA was not seen. Compared with AA, resistance to systemic antibiotics significantly increased in placebo patients (P = 0.03). Compared with placebo, AA significantly reduced Clinical Pulmonary Infection Score (mean ± SEM, 9.3 ± 2.7 to 5.3 ± 2.6 vs. 8.0 ± 23 to 8.6 ± 2.10; P = 0.0008).In chronically intubated critically ill patients, AA successfully eradicated existing MDRO organisms and reduced the pressure from systemic agents for new respiratory resistance. Clinical trial registered with www.clinicaltrials.gov (NCT 01878643).
Ventricular Septal Rupture after Myocardial Infarction
Authors: Duane S Pinto, Thomas M Tu
Journal: New England Journal of Medicine (2002)

Figure 1. Chest pain and diaphoresis developed in an 81-year-old woman with chronic renal insufficiency and hypertension. Although the chest pain resolved, she saw her primary care physician three days later because of profound fatigue. She had a loud holosystolic murmur on physical examination. A 12-lead electrocardiogram demonstrated ST-segment elevation and Q waves in leads II, III, and aVF. The creatine kinase level was 274 U per liter, with an MB fraction of 23 U per liter, and the cardiac troponin I level was more than 50 ng per milliliter. Cardiac catheterization revealed critical single-vessel disease of the right coronary . . .
Human Siglec-10 can bind to vascular adhesion protein-1 and serves as its substrate
Authors: Elina Kivi, Kati Elima, Kristiina Aalto, Yvonne Nymalm, Kaisa Auvinen, Erkki Koivunen, Diana M. Otto, Paul R. Crocker, Tiina A. Salminen, Marko Salmi, Sirpa Jalkanen
Journal: Blood (2009)
Different regulation of free fatty acid levels and glucose oxidation by the Trp64Arg polymorphism of the β3-adrenergic receptor gene and the promoter variant (A-3826G) of the uncoupling protein 1 gene in familial combined hyperlipidemia
Authors: Jussi Pihlajamäki, Johanna Rissanen, Raisa Valve, Sami Heikkinen, Leena Karjalainen, Markku Laakso
Journal: Metabolism (1998)
Biphasic emergence of active tuberculosis in rheumatoid arthritis patients receiving TNFα inhibitors: the utility of IFNγ assay
Authors: Der-Yuan Chen, Gwan-Han Shen, Yi-Ming Chen, Hsin-Hua Chen, Chia-Wei Hsieh, Joung-Liang Lan
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> The risk of active tuberculosis increases in rheumatoid arthritis (RA) patients receiving antitumour necrosis factor alpha (TNFα) therapy. Longitudinal data concerning serial interferon γ (IFNγ) assays for detecting tuberculosis have been limited. This study investigated the time course of the development of active tuberculosis, and evaluated the utility of serial QuantiFERON-TB Gold (QFT-G) assays for detecting its emergence in RA patients undergoing long-term anti-TNFα therapy. <h3>Methods</h3> 242 RA patients who received anti-TNFα therapy and serial QFT-G assays were prospectively evaluated. QFT-G was performed by measuring IFNγ levels in whole blood treated with tuberculosis-specific antigens. <h3>Results</h3> Among 242 RA patients, 75 (31.0%) had a positive tuberculin skin test (TST) and 45 (18.6%) had positive QFT-G results, with another nine (3.7%) showing indeterminate QFT-G assay. Isoniazid prophylaxis was given to 37 patients with TST+/QFT-G+ results and 24 TST+/QFT-G− patients with TST induration diameter ≧10 mm. Four patients (three with baseline QFT-G+ results) developed tuberculosis within the first 3 months of anti-TNFα therapy, whereas five patients with baseline TST−/QFT-G− results developed active tuberculosis after 20–24 months9 anti-TNFα therapy. Progressively rising levels of released IFNγ (2.17±0.98 vs 5.93±2.92 IU/ml in early secretory antigenic target-6-stimulated well; 1.12±0.84 vs 2.96±1.02 IU/ml in culture filtrate protein-10-stimulated well) were observed in those who developed tuberculosis early in anti-TNFα therapy. QFT-G conversion was found in baseline QFT-G-negative patients who developed tuberculosis late in treatment. <h3>Conclusion</h3> The emergence of active tuberculosis follows a biphasic pattern. Persistently high levels of released IFNγ or QFT-G conversion strongly indicate the development of active tuberculosis in patients undergoing long-term anti-TNFα therapy.
EFFECT OF THYROID MEDICATION ON BRAIN METABOLISM OF CRETINS
Authors: H. E. HIMWICH, C. DALY, J. F. FAZEKAS, H. C. HERRLICH
Journal: American Journal of Psychiatry (1942)

Brain metabolism of cretins was studied before and after the administration of desiccated thyroid. Blood was collected from an artery and the internal jugular vein and analyzed for oxygen. Cerebral blood flow was estimated with the aid of a thermostromuhr inserted in the internal jugular vein. The oxygen uptake was also determined and sustained an average rise of 22 per cent after therapy, taking the premedication value as a base line. The deviations from standard values of basal metabolic rate are also presented. The average of 29 arterio-venous oxygen differences of 11 cretins was 5.74 volumes per cent before thyroid administration and that value was reduced to 4.69 volumes per cent on 25 observations on 9 patients after therapy. In 8 cretins the average acceleration of cerebral blood flow was 57 per cent. Alterations of brain metabolism were determined by taking into consideration the changes of the arterio-venous oxygen difference and blood flow. An average increase of 32 per cent in cerebral metabolism was thus revealed as a result of the administration of thyroid. This increase in cerebral metabolism affords a basis for alterations in the cerebral electrical potentials and psychological reactions of these patients. The electroencephalograms disclosed a rise of the energy level in certain frequency ranges. Psychologically, improvement was either absent or of questionable significance in any of the higher processes. The greatest change was that of an acceleration of psychological activity, an acceleration made possible by the increased energy expenditures stimulated by thyroid medication.
Valve Replacement for Aortic Stenosis in Patients With Poor Left Ventricular Function : Comparison of Early Changes With Stented and Stentless Valves
Authors: J. Collinson, M. Henein, M. Flather, J. R. Pepper, D. G. Gibson
Journal: Circulation (1999)

Long-standing aortic stenosis causes significant left ventricular (LV) dysfunction, which may progress irreversibly. In many cases, LV function can be salvaged by aortic valve surgery, although debate exists regarding the best valve prosthesis to use.We studied 33 patients retrospectively who had significant aortic stenosis and impaired LV systolic function, as assessed by transthoracic Doppler echocardiography. Patients were assessed preoperatively and before discharge from the hospital. A total of 20 patients received a stentless (homograft or Toronto) valve, and 13, a stented valve. No patient had significant aortic regurgitation or other valvular disease. Preoperatively, fractional shortening was 18.8+/-5.5% in the stentless group and 18.6+/-3.8% in the stented group. Postoperatively, it was 25.6+/-6.9% (P<0.001 compared with baseline) and 17.0+/-2.8%, respectively (P<0.001 compared with stentless group). Fractional shortening improved because of a reduction in LV end-systolic and end-diastolic dimensions in the stentless group. Systolic long axis function at the LV free wall also recovered, with an increase in systolic excursion and both peak shortening and lengthening rates. No change was noted in mitral valve Doppler patterns.Patients who received a stentless valve demonstrated a significantly greater early improvement in LV systolic function compared with those who received a stented valve.
UN report warns that AIDS epidemic is still out of control
Authors: H. Matthews
Journal: BMJ (1998)

A report published this week by the United Nations and the World Health Organisation shows that there has been little progress in preventing the transmission of AIDS. New drugs have increased survival times for patients in developed countries, but in some parts of Africa the epidemic threatens to reverse gains achieved by development programmes.

The report by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the WHO recorded six million new HIV infections …
Theophylline increases oxygen consumption during inspiratory resistive loading.
Authors: S Janssens, E Derom, J Vanhaecke, M Decramer
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The effect of theophylline on diaphragmatic blood flow (Qdi) and oxygen consumption (VO2di) was studied in eight lightly anesthetized dogs during quiet breathing and inspiratory resistive loading. Qdi was determined with the radioactive microsphere tracer technique, and VO2di was calculated as the product of Qdi and the diaphragmatic arterio-venous oxygen difference. During quiet breathing, theophylline increased minute ventilation (9.3 +/- 1.7 versus 5.1 +/- 0.4 L/min), mean inspiratory flow (547 +/- 60 versus 378 +/- 56 ml/s), and duty cycle (0.270 +/- 0.042 versus 0.192 +/- 0.024) but did not significantly alter Qdi or VO2di. Conversely, Qdi increased significantly during loaded breathing compared with quiet breathing (37 +/- 4 versus 27 +/- 3 ml/100 g/min) and was further increased by theophylline (45 +/- 7 ml/100 g/min). Theophylline did not alter the tension-time index of the diaphragm (TTdi) during inspiratory resistive loading (0.054 +/- 0.006 versus 0.056 +/- 0.004, p NS) but resulted in a disproportionate and significant increase in VO2di (2.66 +/- 0.53 versus 1.78 +/- 0.26 ml/100 g/min). Similarly, total-body oxygen consumption (VO2TB) during inspiratory loading increased significantly after theophylline (24%), but the tension-time index of the inspiratory muscles (TTi), a measure of the total respiratory load, was unchanged. We conclude that theophylline significantly increases VO2di and VO2TB at the same TTdi and TTi during resistive loading. This enhanced energy expenditure needs consideration in the clinical management of pulmonary disorders that increase the work of breathing.
Points: Absolute contraindications to pertussis immunisation?
Authors: J B P Stephenson
Journal: BMJ (1983)

write: Dr Lightman (6 August, p 422) has missed the point.We were not reviewing the variety of lesions that might provoke hot flushes.The object of our case presentation (23 July, p 262) was the objective demonstration that climacteric flushing in a man was associated with circulatory responses virtually identical to those we had shown during the meno- pausal hot flush.'Every blush is not a flush, however, and until the phenomena reported in different circumstances in either sex are recorded by tech- niques capable of following the rapid circulatory changes that occur during the hot flush our under- standing of the mechanisms responsible for the menopausal hot flush will remain obscure.
TV: Horizon: Trial and Error
Authors: A. Kent
Journal: BMJ (2003)

BBC 2, 27 February at 9 pm Rating: ![Graphic][1]</img>![Graphic][2]</img> The notion of gene therapy—the “overpowering” of a defective gene with a correct copy—is beguilingly simple. For patients with life threatening genetic diseases and for doctors frustrated by their inability to intervene and change the course of the disorder, attacking the underlying biology and dealing with the condition at source is an attractive and potentially effective option. For scientists, the opportunity to work in frontier biology with the possibility of creating platform technologies that may cure disease has inspired some of the brightest and best minds. But is gene therapy, as this Horizon programme claimed, the “miracle that crashed into tragedy”? The programme told the story of Jesse Gelsinger, a young man with OTC (ornithine transcarbamylase) deficiency. He entered a gene therapy trial in the … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Preliminary Observations on the Therapy of the Myeloid Blast Phase of Chronic Granulocytic Leukemia with Plicamycin and Hydroxyurea
Authors: Charles A. Koller, Donald M. Miller
Journal: New England Journal of Medicine (1986)

We observed a dramatic improvement in the peripheral blood counts of a patient in the myeloid blast phase of chronic granulocytic leukemia after plicamycin (mithramycin) therapy of concurrent hypercalcemia. We then treated eight additional patients in the blast phase of chronic granulocytic leukemia with a combination of alternate-day plicamycin and daily hydroxyurea. All six patients with myeloid morphology at the time of blast crisis responded with a return to a chronic phase without an intervening pancytopenic period. Of three patients with lymphoid morphology at the time of treatment, only one responded (this patient had recently relapsed and converted from myeloid to lymphoid morphology). Another patient with nonmyeloid, nonlymphoid blast morphology also did not respond. Continual therapy with the two-drug combination appeared to be necessary, since early relapses were seen in responding patients whose therapy was interrupted. These data are preliminary and will need further confirmation, but they suggest that the combination of alternate-day plicamycin and daily hydroxyurea may be effective in the myeloid blast phase of chronic granulocytic leukemia.
Comparative analysis of the expression of ERBIN and Erb-B2 in normal human skin and cutaneous carcinomas.
Authors: S. Lebeau, I. Masouye, M. Berti, E. Augsburger, J-H. Saurat, L. Borradori, L. Fontao
Journal: British Journal of Dermatology (2005)

Background ERBIN is a binding partner of Erb-B2, an orphan receptor within the Erb-B family critically involved in the regulation of cell growth and differentiation. Although its function remains unclear, ERBIN is thought to affect the polarity of epithelial cells and cell growth via the Ras signalling pathway. Objectives To examine and compare the tissue distribution and the expression levels of ERBIN and Erb-B2 in normal skin and in cutaneous carcinomas. Methods Fifteen cases of basal cell carcinoma (BCC), 12 cases of squamous cell carcinoma (SCC) and five cases of keratoacanthoma (KA) were analysed by immunohistochemistry on paraffin-embedded sections using anti-ERBIN and anti-Erb-B2 antibodies. Results ERBIN and Erb-B2 had a similar distribution in normal human skin. They were primarily localized at the plasma membrane in differentiated keratinocytes and in duct cells from eccrine glands, whereas they were localized diffusely in the cytoplasma of basal keratinocytes. In both SCC and KA the subcellular distribution of ERBIN and Erb-B2 remained unchanged, whereas both proteins were redistributed from the plasma membrane into cytosolic aggregates in BCC. Conclusions The subcellular localization of ERBIN in normal human skin is similar to that of Erb-B2 and varies with cell differentiation. Based on our findings and on the biological activities of Erb-B2, it is conceivable that disturbed expression or functioning of ERBIN and Erb-B2 is implicated in the development of the malignant phenotype of BCC.
Cardiac Problems in Pregnancy
Authors: Norbert Gleicher
Journal: JAMA (1984)

UNTIL very recently fetal cardiology was restricted to the study of the embryology of the fetal heart with the primary emphasis on the understanding of the development of structural congenital cardiac abnormalities. Cardiology, and in this sense pediatric cardiology, started with the birth process and was again primarily directed toward recognition, diagnosis, and therapy of neonatally recognized structural congenital heart problems. During the last decade, the fetal heart has attracted increasing interest both on the part of the obstetrician-perinatologist and the pediatric cardiologist. Research into the developing heart has concentrated on embryology but has covered such important areas as the biophysics of the developing heart, the autonomic control of fetal cardiac activity, as well as genetic, infectious, metabolic, and environmental causes for congenital heart abnormalities. The advances and the understanding of basic physiology of the fetal heart as well as the development of newer diagnostic means have, in turn, improved
The nature and kinetics of a delayed immune response to purified protein derivative of tuberculin in the skin of lepromatous leprosy patients.
Authors: G Kaplan, S Laal, G Sheftel, A Nusrat, I Nath, N K Mathur, R S Mishra, Z A Cohn
Journal: The Journal of Experimental Medicine (1988)

We have analyzed the nature and kinetics of a delayed, cell-mediated immune response to a purified protein derivative of tuberculin (PPD) in the skin of 154 naturally sensitized patients with lepromatous leprosy. After the intradermal injection of 5 U of PPD, biopsies were taken at 1-21 d and studied for the composition, extent, persistence, and organization of the emigratory cell response by light and electron microscopy. Induration of positive sites occurred promptly, reached a maximum diameter at 4 d, displayed a major extravasatory element, and was evident for as long as 21 d. The cellularity of the site exhibited a biphasic course, reached a maximum at 7 d, involved as much as 70% of the dermis and millions of new cells, and was elevated threefold above preinjection levels at 21 d. The emigratory cells were limited to T cells and circulating monocytes. T cells were more evident as they entered a preexisting lepromatous lesion containing parasitized macrophages and only occasional T cells many of the CD8+ phenotype. The predominant emigratory T cell was CD4+ although CD8+ cells were in evidence. The CD4/CD8 ratio of the lesions started at less than unity and in two distinct steps reached levels as high as 5:1. In most sites CD4+ cells were in the majority at 21 d. A well-defined granulomatous response with epithelioid and giant cells was apparent at 4 d, reached a maximum at 7 d, and involved all PPD sites at this time point. The generation of these differentiated mononuclear phagocytes from newly emigrated monocytes was never observed in the underlying lepromatous lesion but is a constant feature of the tuberculoid leprosy response. Epidermal thickening and keratinocyte proliferation, sequellae of the dermal reaction, reached a maximum at 7 d and gradually resolved by 3 wk. A constant feature of the PPD response was the extensive destruction of preexisting macrophages containing Mycobacterium leprae bacilli or their products. This was associated with the presence of and intimate contact with highly polarized lymphoid cells of unknown phenotype. Cell destruction did not involve other elements of the dermis and spared parasitized Schwann cells. Newly emigrated T cells and monocytes were never seen within the perineural sheath in contact with neural elements. It appears that a single antigenic stimulus leads to a very long-term, defined series of events with distinct temporal patterns. It includes waves of emigratory T cells, the maturation and organization of monocytes, the generation of killer cells, and the extensive destruction of parasitized macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)
Cell size of alveolar macrophages: an interspecies comparison.
Authors: F Krombach, S Münzing, A M Allmeling, J T Gerlach, J Behr, M Dörger
Journal: Environmental Health Perspectives (1997)

Alveolar macrophages (AM) play a critical role in the removal of inhaled particles or fibers from the lung. Species differences in AM size may affect the number and size range of particles/fibers that can be actually phagocytized and cleared by AM. The purpose of this study was to compare the cell size of rat, hamster, monkey, and human AM by selective flow cytometric analysis of cell volume. Resident AM from CD rats, Syrian golden hamsters, cynomolgus monkeys, and nonsmoking, healthy human volunteers were harvested by standard bronchoalveolar lavage procedures. Morphometric analysis of AM was performed using a flow cytometer that generates volume signals based on the Coulter-type measurement of electrical resistance. We found that hamster and rat AM had diameters of 13.6 +/- 0.4 microns (n = 8) and 13.1 +/- 0.2 microns (n = 12), respectively. Comparatively, the AM from monkeys (15.3 +/- 0.5 microns, n = 7) and human volunteers (21.2 +/- 0.3 microns, n = 10) were larger than those from rats and hamsters. The AM from humans were significantly larger (p &lt; 0.05) than those from all other species studied, corresponding to a 4-fold larger cell volume of human AM (4990 +/- 174 microns 3) compared to hamster (1328 +/- 123 microns 3) and rat (1166 +/- 42 microns 3) AM. In summary, we have found marked species differences in the cell size of AM. We suggest that the number and size range of particles/fibers that can be phagocytized and cleared by AM may differ among species due to inherent or acquired species differences in AM cell size.