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Biomedical subjects

J Gage

Publications and source records attributed to J Gage.

At least 19 recordsLinked to original sources
PubMed2001

Suspected iron dextran-related adverse drug events in hemodialysis patients.

Despite the use of recombinant erythropoietin, anemia remains a significant problem for patients with end-stage renal disease, in part related to chronic dialysis-related blood loss and resultant iron deficiency. Because oral iron preparations have been relatively ineffective and poorly tolerated in this population, intravenous (IV) iron dextran has been widely prescribed, despite a finite risk for adverse effects associated with its use. We analyzed data from Fresenius Medical Care North America (FMCNA) clinical variance reports to determine the incidence of suspected iron dextran-related adverse drug events (ADEs) and associated patient characteristics, dialysis practice patterns, and outcomes. We used a case-cohort study design, comparing individuals who experienced suspected ADEs with the overall FMCNA population. Among 841,252 IV iron dextran administrations from October 1998 through March 1999, there were 165 reported suspected ADEs, corresponding to an overall rate of 0.000196%, or approximately 20 per 100,000 doses. Forty-three patients (26%) required an independent emergency department evaluation, 18 patients (11%) required hospitalization, and 1 patient (0.6%) died. Dyspnea (43%), hypotension (23%), and neurological symptoms (23%) were the most common major ADEs; nausea (34%), vomiting (23%), flushing (27%), and pruritus (25%) were the most common other ADEs. ADEs were 8.1-fold more common among patients administered Dexferrum (American Regent Laboratories, Inc, Shirley, NY) compared with those administered InFed (Watson Pharmaceuticals, Phoenix, AZ). In summary, serious adverse reactions to IV iron dextran are rare in clinical practice. The risk appears to depend on the specific formulation of IV iron dextran. Otherwise, iron dextran-related ADEs are difficult to predict.

Humans↗
PubMed2000

(18)O/(16)O and (13)C/(12)C in an ahermatypic deep-water coral Lophelia pertusa from the North Atlantic: a case of disequilibrium isotope fractionation.

The numerous stable isotope studies of scleractinian photosynthetic reef-building corals in tropical seas have demonstrated the complexity of the biological and environmental factors that give rise to their isotopic composition. Scleractinian non-photosynthetic corals of the deep cold water environment might be expected to reflect the more stable physical environment in the deep sea. However, in comparison, little is known about their isotope systematics. The present study concentrates on specimens of Lophelia pertusa from the north-eastern Atlantic, the Norwegian Shelf and Fjord. Aliquots taken from the theca represent time series and show variations in delta(13)C and delta(18)O of up to 4.7 and 2.4 per thousand, respectively. The variations seem to be related to morphological features of branching. The tendency of higher values near the tip of the polyps reported previously was detected only in some samples. The delta(18)O of the corals are in all cases more negative than the equilibrium values. There is a strong correlation between delta(13)C and delta(18)O forming linear arrays. The difference between these arrays is more pronounced in delta(13)C. The covariation of delta(13)C and delta(18)O indicates an overruling 'kinetic isotope effect'. This is in line with the behaviour of some trace elements. This isotope effect should be regarded as one manifestation of variations in partition coefficients dictated by a biological control on mineralisation (such as food or reproduction) rather than changes in the relative contribution of metabolic carbon affecting delta(13)C, and changes in temperature affecting delta(18)O.

Animals↗
PubMed1998

IL-6 receptor (CD126'IL-6R') expression is increased on monocytes and B lymphocytes in HIV infection.

Interleukin-6 (IL-6) is a multifunctional cytokine, with a wide range of effects on various cell types, including several types of cells involved in immune responses. IL-6 is believed to be involved in the pathogenesis of several diseases and may contribute to AIDS pathogenesis in various ways. Elevated levels of IL-6 occur in HIV infection. The objective of this study was to define the distribution of the expression of the 80-kDa alpha subunit of the IL-6 receptor (CD126'IL-6R') on immune cell subpopulations in HIV-infected subjects. CD126 is responsible for IL-6 binding, and its expression determines which cells respond to this cytokine. An elevated number of monocytes, B cells, and CD4 T cells expressing CD126 were seen in the peripheral circulation of HIV-infected subjects when compared to HIV-seronegative control subjects. Also, an increase in the density of CD126 expression was noted on monocytes. Generally, the observed increases in CD126 did not correlate with CD4 levels in HIV-infected subjects or with disease status, with the exception of CD126 expression on CD8 T cells, which was lower in those HIV-infected subjects that had AIDS. In some cases, increased CD126 expressing cells showed higher levels of STAT3 phosphorylation on exposure to recombinant IL-6. These results indicate that greatly elevated levels of CD126-expressing cells, particularly B cells and monocytes, are seen in HIV infection and suggest that the altered expression of CD126 may contribute directly or indirectly to immune dysfunction and to AIDS pathogenesis in HIV infection.

Adult↗
PubMed1998

Proliferation and collagen synthesis of human anterior cruciate ligament cells in vitro: effects of ascorbate-2-phosphate, dexamethasone and oxygen tension.

Clinical and experimental studies demonstrate that injured anterior cruciate ligaments (ACL) do not usually heal and that autografts used to repair the ACL rapidly weaken in the early period and take a long time to regain strength. The aim of this study was to develop an in vitro culture system in which environmental and biochemical factors influencing the proliferation and matrix synthesis of cells derived from human anterior cruciate ligaments can be studied. Primary cultures of human ACL cells were obtained by outgrowth from explants of normal ACL obtained at knee replacement for osteoarthritis in Dulbecco's minimum essential medium (DMEM). The effects of the additives 100 microm L-ascorbic acid-2-phosphate (Asc-2-P) and 10 n m dexamethasone (dex) on proliferation and collagen synthesis were assessed after 4, 8 and 12 days in culture. Ligament cells were grown at 0, 5, 10 and 21%p O(2)in the presence of 100 microm asc-2-P and 10 n m dex. DNA content was assessed using the Hoechst dye method and collagen synthesis by the incorporation of 5 mCi/ml [(3)H]proline after 3, 6 and 12 days in culture. At 21%p O(2), the presence of asc-2-P and dex induced significantly greater (P< 0.01, ANOVA) cell proliferation than with either additives alone. Greatest percentage collagen to total protein synthesis was observed when cells were grown in the presence of asc-2-P only. Least proliferation and percentage collagen to total protein synthesis was seen when both additives were omitted. Greatest cell proliferation was seen when cells were grown in 10%p O(2)and 5%p O(2)was associated with increased collagen synthesis. These results suggest that it is possible to study the effects of environmental and biochemical factors on human ACL healing in vitro. Our data suggest oxygen can influence certain biosynthetic activities of ACL cells. Low oxygen tensions lead to an increase in collagen production by ACL cells. However early responses to injury require extensive cell proliferation which may be activated at higher p O(2). Variation of p O(2)in ligaments during healing may therefore be an important modulator of successful repair.

Anterior Cruciate Ligament↗
PubMed1996

In their own words. Surgeon representatives discuss legislative and regulatory issues. Part II.

This is the second of a two-part series featuring surgeons who serve on panels, committees, and other groups that offer advice or comments on health policy issues to the federal government; Part I appeared in the September 1996 Bulletin. In their own words, these surgeons describe the issue areas they are addressing and their significance to the profession.

Abstracting and Indexing↗
PubMed1994

Developing a charging system for a nursing specialty: ET nursing.

Because of limited resources and economic constraints, justifying the existence of ET nurses has become an economic challenge for hospitals and nurses. To justify the role of the ET nurse, a charging system for enterostomal therapy was developed at a corporate, for-profit hospital. Three months after implementation, an evaluation of the system demonstrated that revenue was generated in excess of the ET nurse's salary.

Accounting↗
PubMed1993

Crisis stabilization services for children and adolescents: a brokerage model to reduce admissions to state psychiatric facilities.

There continues to be an increased interest in developing community-based services for children and adolescents as an alternative to inpatient care. However, there has been much more talk than action in creating such alternatives. This paper describes the success of a crisis stabilization program for children and adolescents in a community mental health center which historically over-utilized the State psychiatric facility for youth. The Crisis Stabilization Program consists of three components: (1) a two-person crisis team, (2) a four-person on-call team for after hours crises, and (3) funds which the crisis team utilized to broker for a wider array of community-based services.

Adolescent↗
PubMed1989

Effect of isometric exercise on cardiac performance and mitral regurgitation in patients with severe congestive heart failure.

Left ventricular performance was studied during isometric exercise in 17 patients with severe congestive heart failure, combining invasive hemodynamic and echo-Doppler techniques. Isometric exercise at 30% of maximum resulted in a decrease in stroke volume index (27.4 +/- 7.1 to 22.7 +/- 7.4 ml/m2), with a significant increase in heart rate from 81 +/- 10 to 92 +/- 14 beats/min and in systemic vascular resistance from 1827 +/- 527 to 2372 +/- 737 dyne.sec.cm-5. A significant rise in pulmonary capillary wedge pressure (18 +/- 9 to 31 +/- 10 mm Hg) was associated with a marked increase in mitral regurgitant volume (14 +/- 11 to 27 +/- 15 ml), calculated as the difference between total stroke volume obtained by two-dimensional echocardiography and forward stroke volume measured by pulsed Doppler at the aortic anulus. During isometric exercise, left ventricular end-diastolic and end-systolic volumes did not change markedly, but the total stroke volume tended to increase from 62 +/- 13 to 67 +/- 13 ml. The increase in mitral regurgitant volume induced by isometric exercise was correlated with the fall in forward stroke volume (r = 0.7, p less than 0.01). Thus a rise in systemic arterial pressure induced by isometric exercise is associated with a decrease in cardiac performance attributable to redistribution of total left ventricular output with an increase in mitral regurgitation and a simultaneous decrease in forward cardiac output.

Aged↗
PubMed1986

Additive effects of dobutamine and amrinone on myocardial contractility and ventricular performance in patients with severe heart failure.

The effects of amrinone, dobutamine, and a combination of the two drugs on peak positive left ventricular dP/dt and left ventricular performance were evaluated in 11 patients with chronic congestive heart failure. When administered alone, both dobutamine (10.9 micrograms/kg/min) and intravenous amrinone (1.9 mg/kg/min) significantly increased left ventricular dP/dt and performance. When compared with dobutamine alone, the addition of amrinone resulted in further increases in left ventricular dP/dt and cardiac index (to 1319 +/- 419 from 1202 +/- 376 mm Hg/sec, p less than .002, and to 3.56 +/- 0.78 from 3.04 +/- 0.67 liters/min/m2, p less than .01, respectively). The combination also induced a further reduction in left ventricular end-diastolic pressure (to 15.3 +/- 11.3 from 18.2 +/- 10.3 mm Hg, p less than .05) when compared with amrinone alone. The combination of dobutamine and amrinone increased heart rate slightly when compared with either drug alone, but did not further reduce systemic arterial pressure when compared with amrinone alone. The dose-response curve of left ventricular dP/dt and performance during titration of dobutamine with and without the addition of intravenous amrinone was evaluated in seven patients. The addition of amrinone to any dose of dobutamine produced higher cardiac index and lower systemic vascular resistance than dobutamine or amrinone alone. Thus, when compared with dobutamine alone in patients with chronic congestive heart failure, the addition of intravenous amrinone to dobutamine results in an additive improvement in left ventricular performance throughout the dose range.

Adult↗
PubMed1982

Plasminogen activator (urokinase) causes vascularization of the cornea.

The presence of a peripheral zone of (presumed intracellular) plasminogen activator in the normal rabbit cornea has suggested that activator, once released, might regulate the permeability of limbal vessels and angiogenesis, by plasmin-dependent pathways. Plasminogen activator (urokinase [UK]) in rabbit serum albumin (RSA) was injected once (20 microliter, 3.7 CTA U) into the corneal stroma, 2 mm from the limbus. Sprouts arose from the engorged circumlimbal vessels (16 of 20 corneas) beginning on the third day and grew into the cornea over the next several days. Histologically, PMNs were observed in association with growing vessels. Contralateral corneas injected with UK (in RSA) previously inactivated by 99.7% with the specific active site inhibitor, Phe-Ala-Arg-chloromethyl ketone showed minimal vessel engorgement or stromal edema and no vascularization (0 to 20 corneas). Injuries to the so-called (plasminogen activator-containing)"critical zone" of the cornea which elicit neovascularization possibly do so by causing extracellular release of endogenous plasminogen activator. Thus, in addition to initiating the destructive events of ulceration, activator might initiate increases in vessel permeability and also neovascularization, which would result in the eventual arrest of ulceration.

Amino Acid Chloromethyl Ketones↗
PubMed1980

Treatment of experimental herpetic interstitial keratitis with medroxyprogesterone.

A model of herpes simplex interstitial keratitis was developed in rabbits sensitized with live herpes simplex virus (HSV) type 2 and challenged intrastromally with live virus. This model was used to evaluate the effects of subconjunctival medroxyprogesterone acetate on the course of the disease and on collagenase levels in the treated corneas. Whether treated prophylactically or therapeutically, the medroxyprogesterone-treated groups had substantially less stromal infiltration and neovascularization than the controls. The clinical effects corresponded with a marked reduction in the polymorphonuclear leukocyte infiltrate histologically, and the suppression of latent and active collagenase activity in the treated corneas cultured in vitro. However, epithelial disease was exacerbated in prophylactically treated animals. Medroxyprogesterone appears to be useful in the treatment of herpetic interstitial keratitis as an anti-inflammatory agent as well as an inhibitor of collagenase production but, like the corticosteroids, it can exacerbate epithelial disease.

Animals↗
PubMed1980

Collagenase levels in a new model of experimental herpetic interstitial keratitis.

A reproducible model of severe herpetic interstitial keratitis was developed by injecting live herpes simplex virus type 2 intrastromally into the corneas of presensitized rabbits. Herpes-infected corneas showed significantly more stromal infiltration and vascularization, iritis, conjunctivitis, and epithelial disease than the control corneas injected with cell supernatant without virus. Levels of total collagenase detected in the culture media of the herpes-infected corneas were high and were similar to those observed previously in alkali-burned rabbit corneas. Unlike alkali-burned corneas, the herpes-infected corneas showed much more of the enzyme in the latent form during the first two days of culture.

Animals↗
PubMed1980

Stromal vascularization prevents corneal ulceration.

Experiments were performed with a model of focal, thermal-induced ulceration to test the clinical impression that vascularization prevents ulceration of the corneal stroma. Slow-release polymers containing a vasoproliferase agent (tumor angiogenesis factor) were placed in corneal pockets 2 mm central to the limbus of albino rabbits. These polymers elicited blood vessel ingrowth up to the implant. Control eyes received empty polymers which caused minimal to no vessel growth. Polymers were removed, and each cornea received a focal, thermal burn placed just central to the polymer site. All control corneas ulcerated: most (79%) developed deep stromal or perforating ulcers. Only 25% of prevascularized corneas developed stromal ulcers, and none was deep or perforating. After thermal burns, vessels in both groups grew at the same linear rate toward the burned area. There was a direct relationship between the distance separating the nearest blood vessel and the burned area at the time of burning and the maximum depth of stromal ulceration. Thus prevention of or less severe stromal ulceration is correlated with the earlier presence of vessels in the burned area.

Angiogenesis Inducing Agents↗
PubMed1980

Evidence for a role of the plasminogen activator--plasmin system in corneal ulceration.

Plasminogen is present in the cornea andcan be activated to plasmin by plasminogen activator. Plasmin is able, in turn, to activate latent collagenase. This system could initiate and perpetuate the collagen degradation of corneal ulceration. This report details evidence for such a system in the cornea. Plasmin has been found to activate latent collagenase from organ cultures of ulcerating rabbit corneas and from fibroblast cultures derived from such corneas. As in the case of activation by trypsin, activation by plasmin results in the conversion of the 40,000 MW latent form to an active species of 23,000 MW. Explants of normal or alkali-burned, ulcerating corneas demonstrated plasminogen-dependent lysis of fibrin clots; frozen sections of such corneas demonstrated that lysis begins in the superficial stroma near the periphery of the cornea. Multiply freeze-thawed ulcerating corneas, but not normal corneas, showed initial lysis, not peripherally but at the ulcer region containing polymorphonuclear leukocytes. The fact that the peripheral lytic pattern existed in corneas that were obtained from eyes prefrozen in liquid nitrogen before excision of the corneas would suggest that plasminogen activator is normally contained in cells in vivo and is not made only in response to tissue injury. There was no correlation between the location of blood vessels or the presence of the corneal endothelium and the plasminogen-dependent lysis. Plasminogen activator from the ulcerating cornea and from fibroblasts was characterized by sodium dodecyl sulfate--gel electrophoresis of its cleavage products of plasminogen. The activator cleaves plasminogen into heavy- and light-chain fragments similar to those produced from plasminogen by urokinase. Plasminogen activator activity was quantitated by a new assay that restricts diffusion of the enzyme to one dimension into a narrow bore tube. The addition of plasminogen daily to cultures of ulcerating corneas resulted in earlier rises of plasminogen activator, collagenase, and collagen degradation fragments in the culture media. Although total plasminogen activator levels were not increased by the addition of plasminogen to culture, levels of both collagenase and solubilized collagen were approximately doubled. It is concluded that the plasminogen activator--plasmin system might play an important role in the destruction of stromal matrix in corneal ulceration.

Animals↗
PubMed1979

Collagenase from corneal cell cultures and its modulation by phagocytosis.

The uptake of latex by fibroblasts in confluent primary culture results in the secretion of collagenase at a linear rate for a prolonged period. Phagocytosis might therefore constitute an important level of collagenase regulation in corneal ulceration. The collagenase in cell cultures is present in a latent form (40,000 MW) like that obtained from organ cultures of ulcerating corneas and can be activated proteolytically. Production of the latent collagenase in cell culture depends upon the presence of serum and diminishes greatly when serum is removed from the medium. Collagenase activity can be demonstrated after the latent collagenase has been separated from serum antiproteases in the media. Alternatively, careful titration of the crude media with trypsin to saturate serum antiproteases, to release collagenase from the complex with alpha 2-macroglobulin, and to activate latent collagenase also results in measurable collagenase activity. The collagenase that is secreted cleaves fibrillar type I collagen and cleaves soluble type I collagen into the typical 3/4 and 1/4 length fragments, as demonstrated by SDS-gel electrophoresis and electron microscopy.

Animals↗