Dose-response relationship and reproducibility of the fall in exhaled nitric oxide after inhaled beclomethasone dipropionate therapy in asthma patients.

STUDY OBJECTIVES: The fractional concentration of exhaled nitric oxide (FENO) is a marker of asthmatic airway inflammation. We determined the dose response and the reproducibility of the FENO fall following inhaled beclomethasone dipropionate (iBDP) therapy in nonsteroid-treated asthmatic patients. STUDY DESIGN: Study A: For four 1-week periods (period 1 to period 4), the following regimens were administered in sequential order to 15 nonsteroid-treated asthmatic patients: period 1, placebo; period 2, 100 microg/d of iBDP; period 3, 400 microg/D of iBDP; and period 4, 800 microg/d of iBDP. Spirometry, FENO, and provocative concentration of methacholine resulting in a 20% fall in FEV(1) (PC(20)) were measured at each of five visits (visit 1 to visit 5). Study B: During four periods, 12 nonsteroid-treated asthmatic patients received placebo treatment for 7 days (period 1), 200 microg/d of iBDP for 14 days (period 2), washout on placebo treatment until the FENO was within 15% of baseline (period 3), and 200 microg/d of iBDP for 14 days (period 4). RESULTS: Study A: Mean FEV(1) rose progressively from 3.10 L (visit 1) to 3.41 L (visit 5; p = 0.001). All iBDP doses caused a significant FEV(1) rise compared to placebo treatment, but with no significant separation of doses using FEV(1). FENO geometric mean (95% confidence limits) fell progressively from 103.5 parts per billion (ppb) (78.5 to 136.7) to 37.4 ppb (29.1 to 48.0) from visit 1 to visit 5 (p = 0.001). All doses of iBDP resulted in a significant change in FENO from placebo treatment, but with significant separation of only the 100-microg and 800-microg doses by FENO. Geometric mean (95% confidence limits) PC(20) rose progressively from 0.01 mg/mL (0.00 to 0.19) to 0.48 mg/mL (0.01 to 8.1) from visit 1 to visit 5 (p = 0.002). All doses of iBDP resulted in a significant change in PC(20) from baseline or placebo treatment, but with no significant separation of active iBDP doses using PC(20). Study B: FENO fell from 111.56 ppb (80.3 to 155.1) to 66.3 ppb (49.2 to 89.5; p < 0.001) from period 1 to period 2, and from 110.2 ppb (79.3 to 153.1) to 61.7 ppb (42.9 to 88.8; p < 0.001) from period 3 to period 4. There were no significant differences between FENO in period 1 and period 3 (p = 0.83) or between period 2 and period 4 (p = 0.220). CONCLUSIONS: FENO was superior to FEV(1) and PC(20) in separating doses of iBDP. The fall in FENO after two identical administrations of iBDP separated by placebo washout was highly reproducible.

Relative bioavailability of danazol in dogs from liquid-filled hard gelatin capsules.

Danazol was dissolved in non-aqueous mixtures containing either polyethylene glycol 400 or polysorbate 80, and filled into hard gelatin capsules at 50 mg concentrations. The bioavailability of these formulations was compared with commercial danazol capsules in a two-way crossover study using young female beagle dogs. Both formulations showed greater oral bioavailability when compared with either the 100 or 200 mg commercial brand of danazol. The bioavailability of the polyethylene glycol 400 and polysorbate 80 formulations was enhanced 3.7 and 15.8 times, respectively, when compared at the 100 mg dose level.

Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer.

PURPOSE: A large proportion of the practice of radiotherapy in the management of metastatic adenocarcinoma of the prostate is associated with palliation of pain from osseous metastases and improving quality of life. Radiation therapy is well known to be effective in treating painful sites and may also be effective in reducing the propensity for adjuvantly treated disease to become symptomatic. Strontium-89 is a systemic radionuclide that has clinical efficacy in the palliation of pain from bony metastases. METHODS AND MATERIALS: The study was a Phase-III randomized placebo control trial performed in eight Canadian Cancer Centers to evaluate the effectiveness of strontium-89 as an adjunct to local field radiotherapy. Patients with endocrine refractory metastatic prostate cancer received local field radiotherapy and either strontium-89 as a single injection of 10.8 mCi or placebo. RESULTS: One hundred twenty-six patients were recruited. No significant differences in survival or in relief of pain at the index site where noted. Intake of analgesics over time demonstrated a significant reduction in the arm treated with strontium-89. Progression of pain as measured by sites of new pain or the requirement for radiotherapy showed statistically significant differences between the arms in favor of strontium-89. Tumor makers including prostate specific antigen, acid phosphatase, and alkaline phosphatase were also reduced in patients receiving strontium-89. A Quality-of-Life analysis was performed as a multivariate data set and demonstrated an overall superiority of strontium-89 with alleviation of pain and improvement in physical activity being statistically significant. Toxicity was evaluated and demonstrated increased hematological toxicity in the group receiving strontium-89. CONCLUSIONS: It is concluded that the addition of strontium-89 is an effective adjuvant therapy to local field radiotherapy reducing progression of disease as evidenced by new sites of pain and the requirement of further radiotherapy and improving quality-of-life and need for analgesic support in this group of patients.

Case management of the anemic patient: epoetin alfa--focus on adequacy of dialysis.

For most patients, therapy with Epoetin alfa reverses anemia and provides them with many benefits, including an improved quality of life. Although some clinicians have expressed concern about the effect of an increased hematocrit on dialysis efficiency, peritoneal dialysis is unaffected, and changes in hemodialysis efficiency are usually not clinically significant. However, close monitoring of the adequacy of dialysis is always warranted. By tracking the results of serum chemistry tests, analyzing trends in urea kinetic modeling, providing patient education, and intervening early when a problem is detected, nurses can help ensure that patients receive the maximum benefit from their treatment regimen.

Use of EPOGEN for treatment of anemia associated with chronic renal failure.

The anemia of chronic renal failure is a major contributor to the symptoms that limit the quality of life and preclude rehabilitation. The primary cause of the anemia of chronic renal failure is an inability on the part of the impaired kidney to produce adequate amounts of erythropoietin. This hormone stimulates the bone marrow to produce red blood cells. EPOGEN (Epoietin alfa), a glycoprotein produced through recombinant DNA technology, corrects this anemia. Its contribution to the care of persons with chronic renal failure is explored.

The Gore-Tex peritoneal catheter: a clinical evaluation and comparison with the Tenckhoff catheter.

In January of 1983, the Gore-Tex (W.L. Gore & Associates, Inc, Flagstaff, Ariz) peritoneal catheter was introduced into the dialysis market. Presently, there is no other peritoneal catheter that offers this unique subcutaneous tunnel design. This catheter has an external and intra-abdominal Silastic (Dow Corning, Midland, Mich) segment and a transcutaneous segment with a flange and cuff of expanded polytetrafluoroethylene (PTFE). This catheter was designed to decrease the incidence of tunnel infections, catheter cuff extrusions, and exit site infections. The clinical experience with 57 Gore-Tex catheters and 47 Tenckhoff catheters at Ohio State University from May 1980 through April 1983 is presented. In addition, the Gore-Tex catheter's surgical insertion technique and postoperative care procedures are described. There was a significant decrease in the incidence of tunnel infections with the Gore-Tex catheter versus the Tenckhoff catheter (0.03 versus 0.21 infections per patient-year, respectively; P less than .05). There was no significant difference between the Gore-Tex catheter and the Tenckhoff catheter with regard to the patient peritonitis rate (1.12 versus 1.38 episodes of peritonitis per patient-year, respectively) or the exit site infection rate (0.65 versus 0.50 infections per patient-year, respectively). There were no cuff extrusions with the Gore-Tex catheter. The decrease in the incidence of tunnel infections with the Gore-Tex catheter suggests that the PTFE barrier inhibits longitudinal bacterial movement and avoids bacterial sequestration. Patients with repeat tunnel infections may benefit from a Gore-Tex catheter placement.

Analysis of a new technique to stabilize the chronic peritoneal dialysis catheter.

A significant cause of morbidity for peritoneal dialysis patients is catheter dysfunction. In our experience, the most common cause of catheter dysfunction was cephalad migration of the catheter tip out of the true pelvis. A new technique for catheter placement that reduces catheter migration from 35% to 6% (P less than .01 chi 2) is described. Our results demonstrate that peritoneal catheters which dysfunction because of catheter flip generally do so in the first 3 months.