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Biomedical subjects

K Costello

Publications and source records attributed to K Costello.

At least 19 recordsLinked to original sources
PubMed2005

Optimization of the safety and efficacy of interferon beta 1b and azathioprine combination therapy in multiple sclerosis.

We conducted an open-label pilot clinical trial to evaluate the safety and efficacy of adding oral azathioprine to the treatment regimen of 15 multiple sclerosis patients breaking through monotherapy with interferon beta-1b. There were no serious adverse events. Gastrointestinal side effects and leukopenia were the most common adverse events and limited dose escalation. There was a 65% reduction in the number of gadolinium-enhanced magnetic resonance imaging (MRI) lesions on combination therapy compared to the baseline values (P =0.003). A total WBC count less than 4800/mm3 was the best predictor of MRI response.

Adjuvants, Immunologic↗
PubMed2004

Multidisciplinary HIV adherence intervention: a randomized study.

Maintaining greater than 95% adherence to antiretroviral medication is necessary in order to have the greatest therapeutic impact on HIV infection. Furthermore, evidence suggests that adherence rates of between 70% and 89% are significantly associated with viral rebound and the development of drug resistance. Adherence rates at and above the 95% level are difficult for patients to achieve and maintain. Our aim was to determine if an adherence intervention could improve adherence among patients attending an ambulatory care clinic at a large public hospital. The intervention was delivered by a multidisciplinary team of health care professionals and consisted of education coupled with the provision of devices designed to assist patient memory and adherence. A crucial component of the intervention consisted of the identification of patient specific barriers to adherence and the development of strategies to circumvent these problems. Adherence was assessed using patient self-report over the past 4, 7, and 28 days and by calculation of the Morisky score. The study was conducted as a randomised controlled trial using the stepped wedge design with a total of 68 subjects randomised to receive the intervention over a 20-week period. Adherence before and after the intervention formed the analysis. There was a significant decrease in the number of missed doses over the past 4 (1.9 to 1.0, p < 0.001), 7 (3.0 to 1.8, p < 0.001) and 28 (7.4 to 4.2, p < 0.001) days and a decrease in the Morisky score, indicating an improvement in medication taking behaviour (1.3 to 0.5 p < 0.001).

Adult↗
PubMed2003

Randomized trial of an adherence programme for clients with HIV.

Our aim was to determine if a comprehensive adherence package improved self reported adherence to antiretroviral therapy. The adherence package included an education programme, individualized planning of regimens, and the opportunity for a patient to choose from a number of adherence aids and reminder devices. A randomized step wedge design was used. Forty-three individuals were randomized to begin the intervention over a five-month period. There was a substantial fall in the number of missed doses reported for the last four days (0.76 to 0.38, P =0.03) and last seven days (1.5 to 0.74, P =0.005) but not for the last 28 days (2.5 to 2.5, P =0.63). There was no statistical difference in the viral load or CD4 lymphocyte count in the period before or after the intervention. The Morisky score during the pre and post intervention periods was significantly different (P =0.006), 2.9 (SD 0.9) and 3.3 (SD 0.8) respectively. This adherence package improved self reported adherence during the last four and seven days.

Adult↗
PubMed2002

Effect of combined IFNbeta-1a and glatiramer acetate therapy on GA-specific T-cell responses in multiple sclerosis.

The combined treatment with interferon beta (IFNbeta) and glatiramer acetate (GA) is of current interest in multiple sclerosis (MS). The therapeutic effect of GA in MS is believed to be mediated by GA-specific Th2 cells. IFNbeta has a significant anti-proliferative effect on GA-induced lymphoproliferation in vitro. Therefore, we examined the possibility that IFNbeta may interfere with the generation and phenotype of GA T-cell responses in MS patients receiving combined therapy. Sixty-six GA-specific T-cell lines (TCL) were generated ex vivo from five MS patients enrolled in an open-label dinical trial of combined IFNbeta/GA treatment. Controls included 83 pretreatment and 131 on-treatment GA-TCL from 11 MS patients treated with GA only, and five GA-TCL generated from four patients receiving IFNbeta-1a monotherapy. IFNgamma and IL-5 (markers of Th1 and Th2 responses, respectively) were assayed by ELISA in GA-TCL supematants. Th1/Th2 bias was defined by the IFNgamma/IL-5 level ratio ( >2 = Th1 bias, <0.5 = Th2 bias, and 0.5-2 = Th0 bias). The frequency with which GA-reactive TCL were generated was 37.0% for the patients in the combination trial compared to 33.3% in the patients receiving GA alone. The mean stimulation index of the GA-TCL was 8.41 (range 2-42) for the combination compared to a mean of 6.29 (range 2-37) for the GA-treated group--a nonsignificant difference. Mean GA-TCL IFNgamma production was significantly lower in all treatment groups compared to pretreatment IL-5 levels were enhanced in all treatment groups compared to pretreatment levels, but the change was not statistically significant. The Th1/Th0/Th2 distribution of GA-TCL was 7%/30%/63% for the GA+IFNbeta group, 8%/9%/83% for the GA group, compared to 48%/21%/31% pre-GA treatment. All five GA-TCL from the IFNbeta-1a monotherapy patients were Th2-biased. We conclude that IFNbeta-1a does not affect the generation of GA-reactive T cells in vivo. Although more Th0 G4-TCL occurred with combination therapy than with G4 treatment alone, both groups shared an overall Th2 bias. Therefore, we speculate that combined therapy is unlikely to reduce the efficacy of GA treatment in MS.

Adjuvants, Immunologic↗
PubMed2001

Glatiramer acetate induces a Th2-biased response and crossreactivity with myelin basic protein in patients with MS.

Glatiromer acetate (GA) is an approved treatment for multiple sclerosis (MS). The proposed mechanism of action is the induction of GA-specific T cells characterized by protective anti-inflammatory Th2 response. We tested this hypothesis in 11 MS patients treated with GA from 1-19 months. Interferon-gamma and IL-5 (markers of Th1 and Th2 responses respectively) were assayed by ELISA in GA-specific T-cell lines (TCL) supernatants. Th1/Th2 bias was defined based on the ratio of IFN-gamma/IL-5 secretion. Fifty-eight pre-treatment and 75 on-treatment GA-specific TCL were generated. On-treatment mean IL-5 levels in GA-TCL increased significantly, whereas those for IFN-gamma were markedly reduced. Consequently, the ratio of IFN-gamma IL-5 also shifted in favor of a Th2 response. The percentage of GA-TCL classified as Th1 was decreased, whereas those classified as Th2 increased on-treatment as compared to pre-treatment. Some GA-specific TCL, (approximately 25%) generated during treatment secreted predominantly IL-5 in response to MBP and the immunodominant MBP peptide 83-99, indicating that these crossreactive antigens can act as partial agonists for GA-reactive TCL. These results strongly suggest that the mechanism of action of GA in MS involves the induction of crossreactive GA-specific T cells with a predominant Th2 cytokine profile.

Cell Line↗
PubMed1993

The Myers-Briggs type indicator--a management tool.

The Myers-Briggs Type Indicator can be an enlightening experience for managers as it uncovers blind spots as well as provides insight into managerial styles. This tool offers a way to build communication patterns that meet nurse managers' needs and the needs of the people they supervise.

Extraversion, Psychological↗
PubMed1991

Stimulation of human polymorphonuclear leukocyte phosphatidylinositol-4-phosphate kinase by concanavalin A and formyl-methionyl-leucyl-phenylalanine is calcium-independent. Correlation with maintenance of actin assembly.

Chemoattractants directly stimulate the enzyme activity that synthesizes phosphatidylinositol-4,5-bisphosphate (PIP2), phosphoinositol-4-monophosphate (PIP) kinase. The present study determined whether stimulation of this enzyme correlates with actin assembly by assessing the calcium dependence of this reaction. Incubation of neutrophils with 5 to 100 micrograms/ml Con A caused a concentration-dependent increase in PIP kinase activity ranging from 1.38- to 3.4-fold. The effective concentration which stimulated PIP kinase by 50% (17 micrograms/ml, EC50) corresponded with the EC50 for Con A-induced superoxide production (32 micrograms/ml). Like chemoattractants, the increase in PIP kinase by Con A was characterized by a 2.6-fold increase in the maximum velocity (Vmax) of the enzyme, and no change in the Km for ATP. The kinetics of FMLP- and Con A-induced filamentous actin formation preceded stimulation of PIP kinase and was sustained over the same time period that this increased enzyme activity was noted. Although transmembrane signaling by FMLP and Con A requires an increase in intracellular calcium for some polymorphonuclear leukocyte (PMN) functional responses, calcium depletion of PMN by incubation with 100 microM Quin 2 A/M and 5 mM EGTA did not prevent the stimulation of PIP kinase by FMLP or Con A. In addition, calcium depletion did not prevent the increase in filamentous actin formation by FMLP and Con A in PMN. These findings demonstrate that Con A increases PIP kinase activity in human PMN and that PIP kinase stimulation and maintenance of actin assembly are independent of calcium fluxes in these cells. Because PIP2 controls the function of the actin-regulatory proteins, profilin and gelsolin, changes in the synthetic rate of PIP2 through regulation of PIP kinase may provide a molecular basis for the prolonged stimulation of actin assembly in human PMN by agonists such as Con A and FMLP.

Actins↗
PubMed1989

Comparative efficacy and bioequivalence of a brand-name and a generic triamterene-hydrochlorothiazide combination product.

The clinical efficacy, safety, and bioavailability of a generic triamterene-hydrochlorothiazide product were compared with those of Dyazide. Thirty patients who had a diagnosis of nonlabile essential hypertension and who were receiving Dyazide (triamterene 50 mg and hydrochlorothiazide 25 mg) were continued on Dyazide maintenance for 16 days to determine the stability of blood pressure control and serum chemistry values. After this baseline period, the subjects were randomized to receive either Dyazide or a generic version for 21 days. They were then crossed over to receive the opposite product for another 21 days. Blood pressures were monitored throughout the study period, and blood samples were taken for measurement of serum electrolytes and of serum triamterene and its major metabolite, hydroxytriamterene sulfate. Hydrochlorothiazide was assayed in 24-hour urine samples. There were no statistically significant differences between regimens in recumbent and standing mean diastolic blood pressures or in mean concentrations of serum potassium, chloride, glucose, creatinine, and uric acid. Area under the concentration-time curve from 0 to 24 hours after drug administration, maximum concentration in serum, and time to achieve maximum concentration in serum did not differ significantly between regimens for triamterene and hydroxytriamterene sulfate. Similarly, there were no significant differences in excretion, maximum rate of excretion, and time to achieve maximum rate of excretion for urinary hydrochlorothiazide. Patients treated with a brand-name fixed-combination product containing triamterene 50 mg and hydrochlorothiazide 25 mg were given a generic formulation without loss of therapeutic efficacy or development of toxicity.

Adolescent↗
PubMedDate not supplied

Nursing management of MS patients receiving interferon beta-1b therapy.

In 1993, recombinant interferon beta-1b (Betaseron, Berlex Laboratories) was approved by the Food and Drug Administration as a treatment for relapsing-remitting multiple sclerosis (MS). Betaseron is the first therapeutic agent licensed for use with therapeutic patients with MS in more than 20 years. Many patients and their families have expressed great interest in obtaining information about this agent. In response, MS centers throughout the United States have developed Betaseron training programs. This article describes how rehabilitation nurses can educate patients and families about Betaseron.

Adjuvants, Immunologic↗
PubMedDate not supplied

[D.L.vo n. 626/94 - Musculoskeletal diseases caused by use of micropipette in laboratory].

The use of manual pipettes has been associated with a high prevalence of upper extremity and neck cumulative trauma disorders (CTD's) and work-related musculoskeletal disorders (WMSD's) among laboratory workers. The primary risk factor for these disorders are poor ergonomics in three specific areas: posture, repetition and force. Federal agencies have issued guidelines for pipetting practices to reduce the risk of injury and WMSD's. Pipette manufacturing have responded to the problem by improving the ergonomics and buttons and plungers that require less forces during operations. Another problem was still open with the traditional axial-design pipette: deviation of body or extremity from an ergonomically favourable neutral position. The new generation of micropipettes solves this problem.

Carpal Tunnel Syndrome↗