tbuckley/cabot-search huggingface dataset:
Late benign intrathoracic gastric perforation after oesophagectomy for carcinoma.
Authors: J L Peters, C Fisher, B R Kenning, J K Pye
Journal: BMJ (1981)

Cimetidine interaction with phenytoinCimetidine inhibits the hepatic microsomal oxidation system in vitro and reduces clearance of drugs metabolised by these enzymes.'In man cimetidine increases the effect of warfarin'' and diazepam.4Phenytoin, a commonly used anticonvulsant with a narrow therapeutic index, is also metabolised by the hepatic microsomal system.We therefore investigated the effect of cimetidine on steady-state plasma phenytoin concentrations in patients with longstanding epilepsy.Patients studied and mean serum phenytoin concentrations ( SD) before, during, and after cimetidine (C) Phenytoin Mean plasma phenytoin (gmol/l)* Case Age dose Other drugs No (years) (mg/day) Before C During C After C 1 27 400 Carbamazepine 74-7±5-8 99-2±6-3t 89-4±11-0 2 20 260 Valproate, primidone 63-8 ±3-1 82-6±6-7t 74-5 ±2-1 3 33 300 Clonazepam, primidone 45-4±39 527 ±4-5t 48-0±0-7 4 63 300 Phenobarbitone 33-8±3-8 40-3±3-5t36-0±0 0 *Therapeutic range ,umol/l (10-20 ,ug/ml). tp <002 compared with value before cimetidine.Conversion: SI to traditional units-Phenytoin: 1 ,umol/l 0-25 ,g/ml.in free urinary phenytoin would be consistent with this.Alternatively, but less likely, cimetidine may have caused an increase in phenytoin bioavailability.Cimetidine and phenytoin are often prescribed, and concurrent administration will therefore occur in some patients.Our findings show that caution is necessary when adding cimetidine to phenytoin treatment, especially when plasma concentrations are already in the upper therapeutic range.
Predictive value of complement profiles and anti-dsDNA in systemic lupus erythematosus.
Authors: A J Swaak, J Groenwold, W Bronsveld
Journal: Annals of the Rheumatic Diseases (1986)

In a prospective study of 143 patients with systemic lupus erythematosus (SLE) the relation between clinical exacerbations, anti-dsDNA levels, and serum levels of complement components, C1q, C4, C3, C5, and C9 was investigated. In 33 out of these 143 patients a major clinical exacerbation of the disease developed. Evaluation of anti-dsDNA levels in relation to disease activity confirmed our earlier finding that anti-dsDNA levels rose before a major exacerbation and decreased after it. In the remaining 110 SLE patients a nearly constant anti-dsDNA level was seen, but none of these patients experienced a major exacerbation. In the 21 SLE patients who developed deterioration in renal function a decrease of C4 followed by decreases of C1q and C3 levels was seen first, starting about 25 to 20 weeks before the first signs of renal involvement. In the 12 SLE patients who developed an exacerbation without renal involvement an inconsistent profile of the complement components C4, C1q, and C3 was observed. C5 levels were hardly affected at all, while C9 levels were in general higher than normal during the exacerbation, irrespective of the type of exacerbation. These results show that, by following the complement and anti-dsDNA profiles, not only can exacerbations be predicted but also a pointer can be obtained about the pattern of disease well before the first clinical signs of an exacerbation appear.
A Case of Phaeochromocytoma
Authors: R. A. C. Owen, G. H. Murray
Journal: BMJ (1955)

CHRISTMAS DISEASE AND FACTOR VIIMEDILSJiRNA 331Our use of serum, rat.her than plasma or whole blood, may call for brief comment here.Both Christmas factor and Factor VII are stable in stored blood, plasma, or serum for considerable periods (Biggs et al., 1952).We have found Christmas factor to be stable in stored oxalated plasma and normal-serum for three weeks.Therefore, any of these fractions may be used in the treatment of Christmas disease,
442. LV Expressing MR Reporter Genes Allows In Vivo Monitoring of Stem Cell Gene Therapy
Authors: Mario Amendola, Letterio S. Politi, Marcello Cadioli, Rossella Galli, Elena Binda, Andrea Falini, Sonia Levi, Giuseppe Scotti, Alessandra Biffi, Luigi Naldini
Journal: Molecular Therapy (2006)
Lack of correlation of plasma norepinephrine and dopamine-beta-hydroxylase in hypertensive and normotensive subjects.
Authors: C R Lake, M G Ziegler, M Coleman, I J Kopin
Journal: Circulation Research (1977)

Dopamine-beta-hydroxylase (DBH) and norepinephrine (NE) have been determined in over 350 plasma samples from 174 subjects while resting supine (basal sample), standing, or exercising. Although increments in both NE and DBH were found with postural change, the further increase in plasma levels of NE during exertion was not attended by any change in levels of DBH. There was no significant correlation between basal levels of DBH and NE nor was there any correlation in their increments after standing or exercising. DBH activity in plasma of subjects with moderate essential hypertension was not different from that of normotensive subjects. It is concluded that plasma DBH is a poor index of acute sympathetic neuronal activity.
Cellular Regulation of Humoral Immunity
Authors: Alan Solomon
Journal: New England Journal of Medicine (1975)

Much of our information about the structure, function, genetics and metabolism of immunoglobulins has come from studies of the homogeneous immunoglobulins associated with malignant diseases of the plasma cell or lymphocyte. Similarly, our understanding of cellular and other humoral factors involved in the immune response has been obtained from studies of patients with congenital or acquired immunodeficiency syndromes and from animals lacking essential cellular or organ components of the immune system — the so-called immunologic "experiments of nature." Over the past two decades we have witnessed a tremendous increase in our knowledge of the immune system with the identification of . . .
Primary Generalized Osteoarthritis
Authors: Robert L. Swezey
Journal: JAMA (1965)

THE FIRST reported recognition of the existence of a polyarticular form of osteoarthritis was in 1805 by Haygarth.<sup>1</sup>Cecil and Archer, in 1926,<sup>2</sup>associated this disorder with the characteristic nodules of the distal and interphalangeal joints described by Heberden<sup>3</sup>in 1802. A reaffirmation and description of this entity by Kellgren and Moore,<sup>4</sup>in their analysis of 120 cases, has greatly stimulated interest and recognition of this disorder. Stecher,<sup>5</sup>in his monumental study of the genetics of Heberden's nodes, has questioned the relationship of a generalized arthritis to Heberden's nodes. Traut, in writing about degenerative arthritis, speaks of "arthritis sicca," and states that "the joint swelling... in a joint affected by degenerative joint disease is classically bony or capsular rather than due to an increased quantity of synovial fluid."<sup>6</sup> <h3>Kellgren's Disease</h3> Primary generalized osteoarthritis (Kellgren's disease) is a disorder of middle-aged women predominantly, the ratio
Correction: Serum Iron Levels and the Risk of Parkinson Disease: A Mendelian Randomization Study
Authors: Irene Pichler, Fabiola Del Greco M., Martin GÃ¶gele, Christina M. Lill, Lars Bertram, Chuong B. Do, Nicholas Eriksson, Tatiana Foroud, Richard H. Myers, Michael Nalls, Margaux F. Keller, Beben Benyamin, John B. Whitfield, Peter P. Pramstaller, Andrew A. Hicks, John R. Thompson, Cosetta Minelli
Journal: PLoS Medicine (2013)

Background: Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions.Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease.We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date. Methods and Findings:We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791.Estimates of their effect on serum iron were based on a recent genome-wide metaanalysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genomewide and candidate gene studies with 20,809 PD cases and 88,892 controls.Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis.We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it.The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%-6%; p = 0.001) per 10 mg/dl increase in serum iron.Conclusions: Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD.Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made.
Chemical Factors in Asthma
Authors: John G. Wiswell, Francis M. Rackemann
Journal: New England Journal of Medicine (1947)

KNOWLEDGE of what takes place within the patient during a paroxysm of asthma or during an attack of urticaria is not at all clear. Such simple matters as the balances of water, salt or acids and bases have been observed in asthma and in other so-called "allergic diseases," but few of the studies are sufficiently controlled to establish any definite conclusions. The fact is that the available data are often conflicting and therefore confusing. For example, some practitioners treat their patients by withholding salt and water, and others by administering salt and water by mouth and by vein, each group . . .
779. High-Capacity Adenovirus/Retrotransposon Hybrid Vectors for Efficient and Stable Gene Transfer
Authors: Edward C. Nwanegbo, Wentao Gao, Simon Barret-Boyes, Paul D. Robbins, Andrea Gambotto
Journal: Molecular Therapy (2004)

Pre-existing Neutralizing antibody (nab) to adenoviral vectors is one of the major limitations to the successful application of the vector in gene Therapy. Assaying for the presence of Neutralizing antibody becomes necessary for priming and also boosting treatment using adenoviral based regimen. Convectional Neutralization assay relies on the inhibition of cytopathic effect (CPE). This takes between 4 to 7 days and has occasionally proved unreliable. A quick and reliable assay is therefore desirable to overcome this hurdle.
Clinical efficacy and immune regulation with peanut oral immunotherapy
Authors: Stacie M. Jones, Laurent Pons, Joseph L. Roberts, Amy M. Scurlock, Tamara T. Perry, Mike Kulis, Wayne G. Shreffler, Pamela Steele, Karen A. Henry, Margaret Adair, James M. Francis, Stephen Durham, Brian P. Vickery, Xiaoping Zhong, A. Wesley Burks
Journal: Journal of Allergy and Clinical Immunology (2009)
74 THE GALLBLADDER DYSFUNCTIONS AND CONTRIBUTES TO IMPAIRED BILE SALT HOMEOSTASIS IN CYSTIC FIBROSIS
Authors: D. Debray, D. Rainteau, S. Lerondel, C. Rey, L. Humbert, V. Barbu, C. Wolf, C.-H. Cottart, C. Housset
Journal: Journal of Hepatology (2009)
Paroxetine Treatment of Generalized Social Phobia (Social Anxiety Disorder)
Authors: Murray B. Stein, Michael R. Liebowitz, R. Bruce Lydiard, Cornelius D. Pitts, William Bushnell, Ivan Gergel
Journal: JAMA (1998)

Context.—The generalized type of social phobia (social anxiety disorder) is a severe and often disabling form of social anxiety that affects approximately 5% of the general population. Earlier research has shown monoamine oxidase inhibitors or benzodiazepines to be effective in treating this condition, but neither has achieved widespread use.Objective.—To compare the efficacy of paroxetine, a selective serotonin reuptake inhibitor, with placebo in adults with generalized social phobia.Design.—Twelve-week, multicenter, randomized, double-blind trial.Setting.—Thirteen centers across the United States and 1 in Canada.Participants.—Between April 13, 1995, and February 28, 1996, 187 persons meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for generalized social phobia were randomized (and 183 returned for at least 1 efficacy assessment) to treatment.Intervention.—After a 1-week, single-blind, placebo, run-in period, patients received a double-blind, 11-week course of either paroxetine or matching-image placebo. The initial daily dosage of paroxetine (or placebo) was 20 mg with increases of 10 mg/d weekly (flexible dosing to a maximum of 50 mg/d) permitted after the second week of treatment.Main Outcome Measures.—Number of responders based on the Clinical Global Impression Global Improvement Item ("much improved" or "very much improved"); mean change from baseline on the Liebowitz Social Anxiety Scale total score.Results.—Fifty (55.0%) of 91 persons taking paroxetine and 22 (23.9%) of 92 persons taking placebo were much improved or very much improved at the end of treatment (odds ratio [OR], 3.88; 95% confidence interval [CI], 2.81-5.36). Mean Liebowitz Social Anxiety Scale total scores were reduced by 39.1% (the mean baseline score of 78.0 declined by a mean of 30.5 points at follow-up) in the paroxetine group compared with 17.4% (the mean baseline score of 83.5 declined 14.5 points at follow-up) in the placebo group, a difference of 21.7% (95% CI, 8.7%-34.7%) favoring paroxetine.Conclusions.—Paroxetine is an effective treatment for patients with generalized social phobia. Short-term (ie, 11-week) treatment results in substantial and clinically meaningful reductions in symptoms and disability. Future research should test whether these may be further reduced by extended treatment or supplementation with specific educational-cognitive-behavioral techniques.
Long-term Angiotensin-Converting Enzyme Inhibition With Fosinopril Improves Depressed Responsiveness to Ca <sup>2+</sup> in Myocytes From Aortic-Banded Rats
Authors: Yutaka Kagaya, Roger J. Hajjar, Judith K. Gwathmey, William H. Barry, Beverly H. Lorell
Journal: Circulation (1996)

Background We have previously shown that long-term ACE inhibition with fosinopril prolongs survival and improves ventricular function despite persistent severe left ventricular pressure overload in ascending aortic–banded rats with left ventricular hypertrophy during the transition from compensation to failure. Methods and Results To study the cellular mechanism of the effects of long-term ACE inhibition on the modification of the transition to failure in pressure-overload hypertrophy, we measured simultaneous intracellular Ca 2+ transients and myocyte shortening in isolated left ventricular myocytes from fosinopril-treated aortic-banded rats (n=9), untreated aortic-banded rats (n=9), and normal age-matched control rats (n=10). Fosinopril therapy was begun 6 weeks after banding and was continued until week 21 after banding, when the animals were killed. Collagenase-dissociated myocytes loaded with indo 1-AM were paced at 3 Hz at 36°C and superfused at [Ca 2+ ] o of 0.6, 1.2, and 3.0 mmol/L. In myocytes from untreated aortic-banded rats, peak systolic [Ca 2+ ] i was higher than in control myocytes, and the relationship between myocyte shortening and [Ca 2+ ] i was depressed relative to control myocytes, implicating impaired responsiveness to Ca 2+ . Long-term fosinopril treatment improved both myocyte shortening and the relationship of shortening to [Ca 2+ ] i ( P &lt;.05 versus myocytes from untreated aortic-banded rats). Maximal Ca 2+ -activated force was depressed in chemically skinned left ventricular fibers from untreated aortic-banded hypertrophied rats relative to age-matched controls but not in the fosinopril-treated aortic-banded rats. Conclusions Long-term ACE inhibition improves responsiveness to Ca 2+ in the presence of normalization of maximal Ca 2+ -activated force in aortic-banded rats subjected to persistent pressure overload. This may contribute to the favorable effects whereby ACE inhibition modifies the transition from compensated hypertrophy to failure.
REPORT OF COMMITTEE ON PROPOSED INTERNATIONAL CONGRESS FOR CONSERVATION OF VISION
Authors: William Campbell Posey
Journal: JAMA (1926)

All properly organized and directed movements and efforts that have for their object the saving of sight are to be approved and should have the support of ophthalmologists. While, generally speaking, therefore, an international congress for the consideration of the subject of conservation of vision, so called, is to be commended and should receive the approval of the section, it is the opinion of your committee that the time is not yet ripe for such an undertaking. The conservation of vision movement, embracing, as it does, not only all that is included in the science of ophthalmology but also all that relates to the subject in an educational, commercial and broadly social sense as well, has not yet been developed and crystallized in this country, at least, into a position where international cooperation could be successfully accomplished. As a first step toward the holding of such a congress, your committee
Perspective on an Altitude Problem
Authors: Milton Landowne
Journal: New England Journal of Medicine (1969)

Four hundred and fifty years ago, Cortez and his followers brought relatively large numbers of unacclimatized men to encounter the associated rigors of cold, physical activity and high altitude. Medical observations do not appear to have been included in the early history of these expeditions, for the initial description of acute mountain sickness is credited to Acosta in 1590. Since then many accounts of this disorder have been written. Although the great majority are anecdotal, autobiographical or literary, careful clinical and experimental reports are also frequent. However, in any one report the numbers at risk are usually relatively few and . . .
A Comparison of the<b><i>in Vitro</i></b>and<b><i>in Vivo</i></b>Activities of IgG and F(ab′)2 Fragments of a Mixture of Three Monoclonal Anti-Her-2 Antibodies
Authors: Camelia I. Spiridon, Sarah Guinn, Ellen S. Vitetta
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We have demonstrated previously that a mixture of three anti-Her-2 monoclonal antibodies (MAbs) that bind to different epitopes on the extracellular domain of Her-2 expressed on a human breast cancer cell line has more potent antitumor activity than the individual MAbs both in vitro and in xenografted severe combined immunodeficient mice. Because the activity of Herceptin is Fc dependent, we determined whether this would also be the case when a mixture of these three anti-Her-2 MAbs was used. Experimental Design: IgG and highly purified F(ab′)2 fragments of the anti-Her-2 MAbs and Herceptin were prepared and evaluated for their ability to induce cell death, inhibit vascular endothelial growth factor secretion, and mediate antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity in vitro. They were also compared for their abilities to induce regression of large BT474 tumors in severe combined immunodeficient mice. Results: All of the F(ab′)2 fragments were &amp;gt;95% pure and, as expected, did not mediate antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity in vitro. The in vitro antiproliferative and proapoptotic effects of the IgGs and F(ab′)2 fragments were similar. In contrast, the IgGs had significant antitumor activity in vivo, whereas their F(ab′)2 fragments were only marginally effective even at 5-fold higher doses to offset their shorter half-lives. Conclusions: These results confirm the importance of the Fc portion of Herceptin for optimal in vivo activity and demonstrate that even a mixture of three anti-Her-2 MAbs that are highly effective at inducing cell death in vitro requires Fc-mediated effector function for optimal in vivo activity.
Treatment of Breast Cancer-Reply
Authors: Jerome A. Urban
Journal: JAMA (1985)

<h3>In Reply.—</h3> The need for long-term, observed follow-up evaluation of a treatment regimen for primary breast cancer is brushed aside by Dr Wizenberg. Many studies indicate little difference in five-year follow-up when different procedures are applied to patients with similar extent of disease. However, inadequate local therapy that results in increased local recurrence is reflected in diminished ten-year survival.<sup>1-3</sup> The study quoted was based on actuarial five-year data, following an average follow-up of only 39 months, which is inadequate for proper evaluation of a therapeutic procedure for breast cancer. The complications of mastectomy Dr Wizenberg mentions—possible anesthetic death, persistent chest wall discomfort, edema of the arm, and limitation of motion of the arm—also accompany lumpectomy with axillary dissection, which is customarily performed before aggressive radiation therapy is directed to the remaining breast tissue.<sup>4</sup> Lymphangiosarcoma of the arm almost never appears, except when radiation therapy follows axillary dissection. Finally,
Defective binding of macrophages to bone in rodent osteomalacia and vitamin D deficiency. In vitro evidence for a cellular defect and altered saccharides in the bone matrix.
Authors: Z Bar-Shavit, A J Kahn, S L Teitelbaum
Journal: Journal of Clinical Investigation (1983)

In the osteomalacic as well as normal skeleton, few osteoclasts are associated with osteoid-covered bone surfaces. The reason for this particular cellular deficit is not clear, but may relate to the inability of osteoclasts and/or osteoclast precursors (monocyte-macrophages) to attach to immature, unmineralized bone matrix, a step apparently essential for normal resorptive activity and osteoclast differentiation. In this study, we have examined cell-bone binding using macrophages (M phi) and bone isolated from vitamin D-deficient rats and hypophosphatemic, osteomalacic mice and from their normal counterparts. The data show that M phi-bone attachment is greatly reduced (P less than 0.001) in both vitamin D deficiency and hypophosphatemia, but that the mechanisms responsible for this reduction are apparently different in the two disorders. In hypophosphatemia, the reduction in binding appears solely attributable to the absence or inaccessibility of bone matrix oligosaccharides or glycoproteins essential to the attachment process. In vitamin D deficiency, on the other hand, not only is the bone matrix defective as a binding substrate, but the M phi, per se, is limited in its capacity to attach to normal, vitamin D-deficient, and hypophosphatemic bone.
The Syndrome of Dextroversion of the Heart
Authors: ROBERT P. GRANT
Journal: Circulation (1958)

On the basis of 3 personal cases and 119 additional cases collected from the literature the difference between dextroversion and mirror-image dextrocardia is outlined. It is concluded that dextroversion is a part of an exceedingly primitive arrest in development that frequently includes other thoracic and abdominal organs as well as intracardiac structures. The defect is altogether different in embryogenesis and anatomic findings from mirror-image dextrocardia.