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J J Murray

Publications and source records attributed to J J Murray.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cleft lip and palate care in the United Kingdom--the Clinical Standards Advisory Group (CSAG) Study. Part 3: speech outcomes.

OBJECTIVE: To summarize speech outcomes in children born with unilateral cleft lip and palate (UCLP) throughout the United Kingdom. DESIGN: Prospective descriptive study on a cross-sectional sample of children. PATIENTS/PARTICIPANTS: Data were collected for 238 5-year-olds (born between April 1, 1989, and March 31, 1991) and 218 12-year-olds (born between April 1, 1982, and March 31, 1984) with complete UCLP. MAIN OUTCOMES: Ratings of intelligibility, nasality, "speech cleft type characteristics" and speech therapy intervention. CONCLUSIONS: Nineteen percent of 5-year-olds and 4% of 12-year-olds were judged to be impossible to understand or just intelligible to strangers. Thirty-four percent of 5-year-olds and 17% of 12-year-olds had at least one serious error of consonant production. Eighteen percent of 5-year-olds and 12-year-olds had consistent hypernasality of mild, moderate, or severe degree. Approximately two-thirds of both age groups had undergone speech therapy.

Child↗
PubMed2001

Cleft lip and palate care in the United Kingdom--the Clinical Standards Advisory Group (CSAG) Study. Part 4: outcome comparisons, training, and conclusions.

OBJECTIVE: A critical appraisal of cleft care in the United Kingdom. DESIGN: Retrospective comparative study. SETTING: All National Health Service cleft centers in the United Kingdom. PATIENTS/PARTICIPANTS: Children born with unilateral complete clefts of the lip and palate between April 1, 1982, and March 31, 1984 (12-year-olds), and April 1, 1989, and March 31, 1991 (5-year-olds). Newly appointed and senior cleft clinicians. MAIN OUTCOME MEASURES: Skeletal pattern, dental arch relationship, success of alveolar bone grafting, dental health, facial appearance, oral health status, patient/parent satisfaction. CONCLUSIONS: This paper highlights the poor outcomes for the fragmented cleft care in the United Kingdom, compared with European centers. There is an urgent need for a review of structure, organization, and training.

Alveoloplasty↗
PubMed2000

Clinical evaluation of paired compomer and glass ionomer restorations in primary molars: final results after 42 months.

OBJECTIVES: To undertake a clinical trial comparing the efficiency of a compomer restoration with a glass ionomer restoration in the management of caries in primary molar teeth. DESIGN: Subjects were admitted to the trial if they required at least one pair of restorations in primary molar teeth. SETTING: Department of Child Dental Health, Newcastle Dental Hospital and School. SUBJECT: Twenty nine children, aged 4-9 years, had 56 pairs of restorations placed between January 1995 and November 1997. METHOD: The durability of the restorations was assessed during a 42-month follow-up period using modified United States Public Health Service criteria. Survival analysis and the McNemar paired test were used to compare the performance of the two restorative materials. RESULTS: The compomer restorations had a higher mean survival time (42 months, SE 1.40) compared with 37 months (SE 1.90) for the glass ionomer restorations and this was significant at the 5% level. The compomer also performed significantly better in terms of anatomical form, marginal integrity, cavo surface discoloration and maintenance of interproximal contact. CONCLUSIONS: The present trial demonstrated that Dyract compomer performed significantly better than Chemfil Superior a glass ionomer cement for all modified United States Public Health Service criteria over a period of 42 months.

Aluminum Silicates↗
PubMed2000

Does better functional result equate with better quality of life? Implications for surgical treatment in familial adenomatous polyposis.

PURPOSE: The main impetus for a patient with familial adenomatous polyposis to choose colectomy with ileorectal anastomosis over ileal pouch-anal anastomosis is the better functional result. However, does better functional result necessarily translate into better overall quality of life? Previous studies of other diseases have demonstrated no such correlation. This study was performed to determine whether any relationship exists between functional result and quality of life in patients with familial adenomatous polyposis after ileorectal anastomosis and ileal pouch-anal anastomosis. METHODS: All patients with familial adenomatous polyposis who underwent colectomy with ileorectal anastomosis or proctocolectomy with ileal pouch-anal anastomosis from 1980 to 1998 were studied. Functional data were obtained by questionnaire. Health-related quality of life was assessed by two validated instruments, the SF-36 Physical and Mental Health Summary Scales and the SF-36 Health Survey, which measure physical and mental functioning and eight separate health-quality dimensions, including health perception, physical and social functioning, physical and emotional role limitations, mental health, bodily pain, and energy or fatigue. RESULTS: Data were obtained in 44 of 68 patients, 14 with ileorectal anastomosis and 30 with ileal pouch-anal anastomosis. No differences were demonstrated between the two groups for patient age, mean follow-up time, and mean patient age at operation. Functional results were worse for the ileal pouch-anal anastomosis group vs. the ileorectal anastomosis group in number of bowel movements per day (7.5 vs. 5.2; P < 0.05), leakage (43 vs. 0 percent; P < 0.01), pad usage (17 vs. 0 percent; P < 0.01), perianal skin problems (33 vs. 7 percent; P < 0.01), food avoidance (80 vs. 43 percent; P < 0.01), and inability to distinguish gas (37 vs. 7 percent; P < 0.01). Results of the health-related quality-of-life surveys, however, demonstrated no difference between the ileal pouch-anal anastomosis and ileorectal anastomosis groups. The Physical and Mental summary scales for the ileal pouch-anal anastomosis and ileorectal anastomosis groups were not significantly different (Physical Health Scale, 50.3 vs. 50.9; Mental Health Scale, 51.7 vs. 49.6), and none of the eight dimensions of the SF-36 health survey demonstrated statistical differences between the ileal pouch-anal anastomosis and ileorectal anastomosis groups. CONCLUSION: Better functional results were not equated with better quality of life in this pilot study. Although patients with the ileorectal anastomosis have better functional results than those with ileal pouch-anal anastomosis, the measured health-related quality of life as determined by a validated generic health-related quality-of-life instrument is the same for both groups. These results suggest that all patients with familial adenomatous polyposis might be optimally treated with an ileal pouch-anal anastomosis. More importantly, this study suggests that health-related quality of life should play a greater role in the evaluation of care and treatment in colon rectal surgery.

Adenomatous Polyposis Coli↗
PubMed2000

Phase III, randomized, double-blind study of clarithromycin extended-release and immediate-release formulations in the treatment of adult patients with acute maxillary sinusitis.

BACKGROUND: Clarithromycin has an established bacteriologic efficacy and safety profile in the treatment of respiratory tract infections. OBJECTIVE: This study compares the efficacy and tolerability of extended-release and immediate-release formulations of clarithromycin in patients with acute maxillary sinusitis. METHODS: Fourteen days' treatment with once-daily clarithromycin was compared with the immediate-release, twice-daily formulation in a phase III, randomized, double-blind, parallel-group, multicenter study. Patients aged > or =12 years with signs, symptoms, and a radiologically confirmed diagnosis of acute maxillary sinusitis were eligible. Patients were assessed before treatment, within 48 hours after treatment, on study days 16 to 18, and at the test-of-cure visit on study days 24 to 31. Patients who received > or =1 dose of study drug were included in the safety analysis. RESULTS: Of 283 patients treated, 245 were included in the efficacy analysis (122 in the extended-release group, 123 in the immediate-release group). Treatment groups were well matched with respect to demographic characteristics and medical condition and history. At the test-of-cure visit, 85% of patients in the clarithromycin extended-release group and 79% in the immediate-release group were deemed clinical cures; 89% and 91% in the extended-release and immediate-release groups, respectively, demonstrated radiographic success. Overall incidences of study drug-related adverse events were similar in the 2 treatment groups (32% in the extended-release group and 28% in the immediate-release group); however, significantly fewer patients receiving extended-release clarithromycin (2/142 11%]), compared with those receiving the immediate-release formulation (10/141 [7%]: P = 0.02) discontinued therapy because of drug-related gastrointestinal symptoms or abnormal taste. No clinically meaningful changes in laboratory values or vital signs were observed during the study. CONCLUSION: Although the efficacy of the 2 formulations was comparable, once-daily clarithromycin extended-release was better tolerated than the twice-daily immediate-release formulation by patients with acute maxillary sinusitis.

Acute Disease↗
PubMed2000

A retrospective study of treatment provided in the primary and secondary care services for children attending a dental hospital following complicated crown fracture in the permanent dentition.

OBJECTIVES: To investigate treatment provision in primary and secondary dental care following complicated crown fracture of permanent teeth. DESIGN AND METHODS: Retrospective observational survey of dental records of all patients attending a dental hospital trauma clinic during a 2-year period with complicated crown fracture. RESULTS: Eighty children (70% male) aged 6-16 years (mean age 10.3 years) with 98 complicated crown fractures were identified. Of these children, 54% were seen for emergency treatment on the day of their injury, 75% within 48 h. Of the 98 injured teeth, 60% were seen initially in general dental practice but only 56% of these 59 cases were provided with emergency treatment in practice, the others being referred immediately to the trauma clinic for treatment. The main cause of fractures was transport, in particular, bicycles. Radiographs were available for 96 teeth; for the 43 open apex teeth, the definitive treatment was pulp capping (44% of cases) and pulpotomy (30%), with vitality maintained in five cases up to 4.8 years after trauma. The 53 closed apex cases were treated definitively with pulp capping (38%) and pulpectomy (36%) and six teeth had maintained their vitality up to 4.3 years after trauma. Sixty-seven per cent of the pulp caps and 47% of the 19 pulpotomies provided relied on a doubtful coronal seal. This was primarily due to the extensive use of a conventional glass ionomer cement as an emergency bandage. The use of an etched or bonded material at initial presentation extended the Median Survival Time for vitality in open apex teeth from 188 to 377 days and in closed apex teeth from 15 to 64 days. CONCLUSIONS: Emergency treatment of complicated crown fractures, particularly in primary care services is often inappropriate or inadequate with regard to emergency management of the exposed pulp and provision of a hermetic coronal seal.

Adolescent↗
PubMed2000

Ethanol increases superoxide anion production stimulated with 4beta-phorbol 12-myristate 13-acetate in human polymorphonuclear leukocytes. Involvement of protein kinase C.

Stimulation of human polymorphonuclear leukocytes (PMNs) with PMA initiates a cascade of events leading to the production and release of superoxide anion (O-2), a major component in anti-bacterial defense. Generation of O-2 by PMA-stimulated PMNs occurs through the translocation and activation of protein kinase C (PKC). In this study, using freshly isolated PMNs, we examined the effect of ethanol on this response to PMA. Our results show that the basal production of O-2 was not affected by ethanol. In contrast, the response induced by PMA was potentiated by ethanol. This potentiation was observed even at high doses of PMA (200 nM) which alone had stimulated the O-2 response maximally. This enhanced response was not due to an increase of PMA uptake by PMNs. The maximal effect was obtained when the cells were preincubated with 80 mM of ethanol before PMA stimulation. Measurement of PKC activity in the cytosolic and membrane fractions showed that pretreatment of PMNs with ethanol increased twofold the PMA-stimulated PKC activity in the membrane fraction. Furthermore, Western blot analysis verified that this increase in PKC activity in the membrane fraction was linked to an increase in the translocation of PKC-alpha and -beta isoforms to the membrane. These results suggest that ethanol potentiates PMA-induced O-2 production through increasing PKC translocation and activity in PMNs.

1-Butanol↗
PubMed2000

Mometasone furoate administered once daily is as effective as twice-daily administration for treatment of mild-to-moderate persistent asthma.

BACKGROUND: Despite current recommendations, many patients with persistent asthma are still treated with bronchodilators alone. OBJECTIVE: The safety and efficacy of two once daily dosing regimens (200 microg and 400 microg) of mometasone furoate (MF) administered in the morning by using a dry-powder inhaler (DPI) were compared with those of a twice daily dosing regimen (200 microg administered twice daily) in patients with mild-to-moderate persistent asthma previously taking only inhaled beta(2)-adrenergic agonists. METHODS: All patients (306 patients; age range, 12-70 years) were given a diagnosis of asthma for at least 6 months before enrollment in this 12-week, placebo-controlled, double-blind, randomized study. The primary efficacy variable was change in FEV(1) from baseline to endpoint (last evaluable visit). RESULTS: At endpoint, FEV(1) was significantly improved (P < or =.02) after MF-DPI 400 microg once daily morning treatment and MF-DPI 200 microg twice daily treatment (16.0% and 16.1%, respectively) compared with placebo (5.5%). The improvement seen with MF-DPI 200 microg once daily morning treatment (10.4%) was not significantly different from that with placebo. Secondary efficacy variables also showed significant improvement for the MF-DPI 400 microg once daily morning treatment group and the MF-DPI 200 microg twice daily treatment group compared with the placebo group. All doses of MF administered by means of a DPI were well tolerated. CONCLUSION: This is the first study to demonstrate that a total daily dose of 400 microg of MF administered by means of a DPI is an effective treatment for patients with mild-to-moderate persistent asthma previously taking only inhaled beta(2)-adrenergic agonists. This treatment was equally effective when administered either as a once daily or twice daily regimen.

Adolescent↗
PubMed2000

Prostaglandin E(2) decreases allergen-stimulated release of prostaglandin D(2) in airways of subjects with asthma.

Prostaglandin E(2) (PGE(2)) inhibits the early and late bronchoconstrictor response to inhaled allergen. The mechanisms of action, however, are not understood. We investigated the effect of inhaled PGE(2) on the release of prostaglandin D(2) (PGD(2)), preformed mast cell mediators, and other products of arachidonic acid metabolism. We compared inhaled PGE(2) (100 microgram) to placebo in a randomized double-blind crossover study. Ten atopic asthmatics underwent bronchoscopy immediately after inhalation of PGE(2) or placebo. Bronchoalveolar lavage (BAL) was performed at baseline, and in a separate segment 4 min after allergen instillation. Nebulized PGE(2) was well tolerated. PGE(2) concentrations in baseline lavage fluid were significantly greater after PGE(2) inhalation than after placebo. PGD(2) concentrations after allergen challenge were significantly reduced in those subjects receiving nebulized PGE(2) compared with control subjects. We conclude that PGE(2) can be safely delivered by inhalation. Nebulized PGE(2) administered before to segmental allergen challenge reduced PGD(2) in BAL fluid (BALF). PGE(2) also decreased the production of other mediators of the arachidonic acid pathway, although not significantly. The reduction of PGD(2) may be part of the mechanism by which PGE(2) blocks the early asthmatic response.

Administration, Inhalation↗
PubMed2000

Sustained reduction in myocardial reperfusion injury with an adenosine receptor antagonist: possible role of the neutrophil chemoattractant response.

Recent studies have demonstrated that three membrane-permeant A(1) receptor antagonists reduced infarct size in a model of ischemia followed by brief reperfusion. However, it was not determined whether cardioprotection was mediated by nonspecific intracellular effects of these highly lipophilic drugs and whether the antagonists only delayed myocardial necrosis without affecting the ultimate infarct size. In the present study, closed-chest dogs were subjected to 90 min of left anterior descending coronary artery occlusion and 72 h of reperfusion and received either a nonmembrane-permeant adenosine receptor blocker that is devoid of direct intracellular effects and is 6-fold selective for the A(1) receptor [1, 3-dipropyl-8-p-sulfophenylxanthine (DPSPX); n = 11] or vehicle (n = 12). DPSPX was administered as three 200-mg boluses 60 min before and 30 and 120 min after reperfusion. The area of necrosis was determined histologically and expressed as a percentage of the area at risk. Baseline predictors of infarct size were similar in the two groups. The ratio of the area of necrosis to the area at risk was less in the DPSPX group (17.8 +/- 4.3% versus 35.0 +/- 1.9%; P =. 012), and DPSPX improved regional ventricular function. Under both basal and stimulated (formyl-Met-Leu-Phe) conditions, suspensions of human neutrophils generated extracellular adenosine levels (approximately 50 nM) sufficient to activate A(1) receptors. Moreover, both DPSPX and 1,3-dipropyl-8-cyclopentylxanthine, a selective A(1) receptor antagonist, significantly reduced the chemoattractant response of neutrophils to formyl-Met-Leu-Phe. We conclude that blockade of A(1) adenosine receptors attenuates myocardial ischemic/reperfusion injury, possibly in part by decreasing the chemoattractant response of neutrophils.

Animals↗
PubMed1999

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with type A-resistant cervical dystonia (CD). BACKGROUND: Local intramuscular injections of BoNT are an effective therapy for CD. After repeated use, some patients become resistant to therapy. BoNT/B, effective in type A toxin-responsive patients, is proposed as an alternative therapy for type A-resistant patients. METHODS: The authors performed a 16-week, double-blind, placebo-controlled trial of BoNT/B in type A-resistant patients with CD. After resistance to therapy was confirmed with the frontalis-type A test, placebo or 10,000 U BoNT/B was administered in a single session into two to four clinically involved muscles. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was the primary efficacy measurement. TWSTRS-Total, three visual analog scales (Patient Global Assessment of Change, Principal Investigator Global Assessment of Change, Patient Analog Pain Assessment), and adverse events were assessed at baseline and weeks 2, 4, 8, 12, and 16. RESULTS: A total of 77 patients participated (38 placebo, 39 active). Improvements in severity, disability, and pain were documented in the BoNT/B-treated group. TWSTRS-Total scores were improved in the BoNT/B-treated group at weeks 4 (p = 0.0001), 8 (p = 0.0002), and 12 (p = 0.0129). All three visual analog scales demonstrated improvements at week 4 (p < 0.0001, 0.0001, and 0.001). A Kaplan-Meier analysis supported a duration of effect of 12 to 16 weeks in the active group. Dry mouth and dysphagia were self-limited adverse effects, reported more commonly in the BoNT/B group. CONCLUSIONS: Botulinum toxin type B (BoNT/B) (NeuroBloc) is safe and efficacious for the management of patients with type A-resistant cervical dystonia with an estimated duration of treatment effect of 12 to 16 weeks.

Adult↗
PubMed1999

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with cervical dystonia (CD). BACKGROUND: BoNT/B is a form of chemodenervation therapy for the treatment of patients with CD. METHODS: The authors performed a 16-week, randomized, multicenter, double-blind, placebo-controlled trial of BoNT/B in patients with CD who continue to respond to botulinum toxin type A. Placebo, or 5,000 U or 10,000 U of BoNT/B was administered in two to four muscles involved clinically in CD. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure. Clinical assessments and adverse events were recorded for treatment day 1 and at weeks 2, 4, 8, 12, and 16. RESULTS: A total of 109 patients were enrolled randomly across all three treatment groups. The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 (placebo), 9.3 (5,000 U), and 11.7 (10,000 U). For the prospectively defined primary contrast (10,000 U versus placebo), highly significant differences were noted for the primary (TWSTRS-Total, baseline to week 4, p = 0.0004) and supportive secondary (Patient Global Assessment, baseline to week 4, p = 0.0001) outcome measures. Improvement in pain, disability, and severity of CD occurred for patients who were treated with BoNT/B when compared with placebo-treated patients. Overall, improvements associated with BoNT/B treatment were greatest for patients who received the 10,000-U dose. The duration of treatment effect for BoNT/B was 12 to 16 weeks for both doses. CONCLUSION: Botulinum toxin type B (NeuroBloc) is safe and efficacious at 5,000 U and 10,000 U for the management of patients with cervical dystonia.

Adult↗
PubMed1999

Effects of 60 Hz magnetic field exposure on polymorphonuclear leukocyte activation.

We have investigated the effects of a sinusoidal 60 Hz magnetic field on free radical (superoxide anion) production, degranulation (beta-glucuronidase and lysozyme release) and viability in human neutrophils (PMNs). Experiments were performed blindly in very controlled conditions to examine the effects of a magnetic field in resting PMNs and in PMNs stimulated with a tumor promoter: phorbol 12-myristate 13-acetate (PMA). Exposure of unstimulated human PMNs to a 60 Hz magnetic field did not affect the functions examined. In contrast, exposure of PMNs to a 22 milliTesla (mT), 60 Hz magnetic field induced significant increases in superoxide anion (O2-) production (26.5%) and in beta-glucuronidase release (53%) when the cells were incubated with a suboptimal stimulating dose of PMA. Release of lysozyme and lactate dehydrogenase was unchanged by the magnetic field, whether the cells were stimulated or not. A 60 Hz magnetic field did not have any effect on O2- generation by a cell-free system xanthine/xanthine oxidase, suggesting that a magnetic field could upregulate common cellular events (signal transduction) leading to O2- generation and beta-glucuronidase release. In conclusion, exposure of PMNs to a 22 mT, 60 Hz magnetic field potentiates the effect of PMA on O2- generation and beta-glucuronidase release. This effect could be the result of an alteration in the intracellular signaling.

Adult↗
PubMed1999

Laparoscopic colectomy: indications for conversion to laparotomy.

HYPOTHESIS: Although experience with laparoscopic colectomy continues to accumulate, criteria for patient selection for the procedure have yet to be developed. We propose that review of indications for conversion to laparotomy during laparoscopic colectomy should define some of the current technical limitations of the procedure. This information may facilitate development of selection criteria for laparoscopic colon and rectal surgery. DESIGN: Single-institution retrospective medical records review. SETTING: Tertiary referral center. PATIENTS: Two hundred patients who underwent laparoscopic colon surgery, in 47 (23.5%) of whom the procedure was converted to laparotomy. INTERVENTIONS: A registry of 200 patients who have undergone laparoscopic colon surgery was analyzed. Medical records of 47 patients whose procedure was converted were reviewed to assess indications for conversion and identify factors contributing to the need for conversion. RESULTS: Between July 1, 1991, and September 30, 1998, 200 laparoscopic colon procedures were performed: 78 ascending colectomies, 74 descending or sigmoid colectomies, 14 diverting stomas, and 34 "other procedures." The 200 patients were divided into 4 cohorts of 50 consecutive patients to analyze changes with time. The conversion rate was statistically greater in the first quarter (18 patients [36.0%]) than in subsequent quarters (16.0%; P <.05). The rate of conversion to laparotomy for segmental resection of the ascending and descending colon (31/153 [20.3%]) has been equivalent and less than the conversion rate for other procedures (16/33 [48.5%]; P <.05). The distribution of patients by operative indication has been fairly constant. The indication for operation has not influenced the need for conversion. The indications for conversion were technical problems in 15 patients (hypercarbia, unclear anatomy, and stapler misfire), laparoscopic complications in 9 patients (bleeding, cystotomy, and enterotomy), and problems that exceeded the limits of laparoscopic dissection in 23 patients (phlegmon, adhesions, obesity, and adjacent organ involvement by cancer). CONCLUSIONS: Our conversion rate has decreased during our experience, and currently the need for conversion to laparotomy is most frequently caused by situations such as excessive tumor bulk, adhesions, and diverticular phlegmon that exceed the technical limitations of laparoscopic dissection. Colorectal reanastomosis following a Hartmann resection and procedures involving resection of the distal rectum are unlikely to be successfully completed. Although obesity accentuates the technical limitations of laparoscopic dissection, it is an infrequent cause for conversion to laparotomy.

Colectomy↗
PubMed1999

Allergen-induced synthesis of F(2)-isoprostanes in atopic asthmatics. Evidence for oxidant stress.

It is thought that reactive oxygen species (ROS) participate in the inflammation which characterizes asthma, but the evidence supporting this contention is incomplete. F(2)-isoprostanes (F(2)-IsoPs) are arachidonate products formed on membrane phospholipids by the action of ROS and thereby represent a quantitative measure of oxidant stress in vivo. Using a mass spectrometric assay we measured urinary release of F(2)-IsoPs in 11 patients with mild atopic asthma after inhaled allergen challenge. The excretion of F(2)-IsoPs increased at 2 h after allergen (1.5 +/- 0.2 versus 2.6 +/- 0.3 ng/mg creatinine) and remained significantly elevated in all urine collections for the 8-h period of the study (analysis of variance [ANOVA]). The measured compounds were of noncyclooxygenase origin because neither aspirin nor indomethacin given before challenge suppressed them. Urinary F(2)-IsoPs remained unchanged after inhaled methacholine challenge. In nine atopic asthmatics, F(2)-IsoPs were quantified in bronchoalveolar lavage fluid (BALF) at baseline values and in a separate segment 24 h after allergen instillation. F(2)-IsoPs were elevated late in the BALF (0.9 +/- 0.2 versus 11.4 +/- 3.0 pg /ml, baseline versus allergen, respectively, p = 0.007). The increase was inhibited by pretreatment of the subjects with inhaled corticosteroids. These findings provide a new evidence for a role for ROS and lipid peroxidation in allergen-induced airway inflammation.

Administration, Inhalation↗
PubMed1999

Fluticasone alone or in combination with salmeterol vs triamcinolone in asthma.

OBJECTIVES: To compare the efficacies of medium-dose fluticasone propionate (FP), medium-dose triamcinolone acetonide (TAA), and combined low-dose FP plus salmeterol (SL). DESIGN: Randomized, double-blind, triple-dummy, multicenter, 12-week clinical trial. SETTING: Allergy/respiratory care clinics. PATIENTS: Six hundred eighty patients with asthma previously uncontrolled with low-dose inhaled corticosteroids. INTERVENTIONS: FP, 220 microg bid; TAA, 600 microg bid; or FP, 88 microg plus SL, 42 microg bid. MEASUREMENTS AND RESULTS: Outcome measures included FEV1, peak expiratory flow (PEF), supplemental albuterol use, nighttime awakenings, asthma symptoms, and physician global assessment. Compared with TAA, 600 microg bid, treatment with FP 220, microg bid, significantly increased FEV1, morning and evening PEF, and percent symptom-free days, and significantly reduced rescue albuterol use, number of nighttime awakenings, and overall asthma symptom scores (p < or = 0.035). Improvements with low-dose FP, 88 microg, plus SL, 42 microg bid, were significantly (p < or = 0.004) greater than TAA, 600 microg bid, in all the aforementioned efficacy measures as well as percent of rescue-free days. Combined low-dose FP, 88 microg, plus SL, 42 microg bid, also significantly increased FEV1 and percent of rescue-free days, and significantly reduced albuterol use compared with medium-dose FP, 220 microg bid (p < or = 0.018). At endpoint, both FP, 220 microg bid, and FP, 88 microg, plus SL, 42 microg bid, significantly increased FEV1 by 0.48 L and 0.58 L, respectively, compared with 0.34 L with TAA, 600 microg bid. CONCLUSION: In patients who are symptomatic while taking low-dose inhaled corticosteroids, medium-dose FP (440 microg/d) and combination treatment with low-dose FP (176 microg/d) plus SL (84 microg/d) are both more effective than medium-dose TAA (1200 microg/d) in improving pulmonary function and asthma symptom control.

Administration, Inhalation↗
PubMed1999

Inhibition of stimulated interleukin-2 production in whole blood: a practical measure of cyclosporine effect.

BACKGROUND: Prediction of cyclosporine (CSA) efficacy and toxicity in individual patients is difficult. There is no practical, biologically relevant, pharmacodynamic measure of CSA effect. A major effect of CSA is to decrease interleukin-2 (IL-2) production; however, measurement of this effect in isolated lymphocytes as a marker of response to CSA has been problematic. METHODS: CSA inhibition of phytohemagglutinin-P (PHA)-stimulated IL-2 production, measured by ELISA, was studied ex vivo in whole blood drawn before, and after subjects received 4 mg/kg oral CSA. RESULTS: Four hours after CSA was administered, the mean (+/- SD) CSA concentration was 702 +/- 196 microg/L and PHA-stimulated IL-2 production decreased by 68.7% +/- 17.2% (P <0.0001; n = 17). Twenty-four hours after CSA was administered, concentrations were low (64 +/- 24 microg/L), with no inhibition of IL-2 production. A rapid, concentration-dependent response occurred. Maximum CSA concentrations (944 +/- 187 microg/L) and maximum inhibition of IL-2 production (86.9% +/- 13.7%) occurred 90 min after subjects received CSA. In vitro, 32.5-1200 microg/L CSA also inhibited PHA-stimulated IL-2 production in whole blood in a dose-dependent fashion with a similar IC(50) (approximately 300-400 microg/L) ex vivo and in vitro. CONCLUSION: In the search for a pharmacodynamic marker to better guide immunosuppressive therapy, the relationship between this simple, biologically relevant measure of CSA effect and clinical outcome should be determined.

Biomarkers↗