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Biomedical subjects

C D Brooks

Publications and source records attributed to C D Brooks.

15 recordsLinked to original sources

Unilaterality of obstruction after acute nasal allergen provocation. Relation of allergen dose, nasal reactivity and the nasal cycle.

We examined unilaterality of obstruction after acute bilateral nasal allergen provocation in two groups of pollen-sensitive volunteers studied out of season. One group was challenged on one occasion with a threshold allergen dose and on another with placebo. We measured nasal airway resistance (NAR) unilaterally for 3.5 hr before the challenges and for 40 min after. Most subjects' noses had marked asymmetry of response. Over half showed marked obstruction on one side and none at all on the other side. The side which showed higher resistance and greater lability before challenge was typically more obstructed after. In a second group we compared responses to threshold and x 10 threshold doses. Threshold challenge produced results similar to those seen with the first group. After the higher allergen dose, there was some obstruction in the less responsive side and the rate of rise was much slower. Obstructive response after acute threshold allergen challenge is typically one-sided. This pattern may be related to the stage of the nasal cycle in which the challenge was delivered. Higher allergen doses produce more obstruction in the less responsive side but the response is still asymmetrical.

Airway Resistance

Clinical safety of flurbiprofen.

Data from 58 premarketing studies of the nonsteroidal antiinflammatory drug flurbiprofen were pooled for analyses of adverse drug reactions (ADRs). These studies included 5602 patients treated with flurbiprofen (N = 4123), aspirin (N = 1033), or placebo (N = 446) for varying durations. Diagnoses included rheumatoid arthritis, osteoarthritis, and other painful musculoskeletal conditions. In these studies serious upper gastrointestinal ADRs occurred in flurbiprofen-treated patients at less than one half the rate seen in aspirin-treated patients. The incidence of serious urinary tract ADRs was lower with flurbiprofen than with aspirin. The flurbiprofen group had no serious clinical ADRs related to the hemic/lymphatic system. The most common laboratory abnormality was a decrease in hematocrit, which occurred less often than in the aspirin group. We also evaluated serious flurbiprofen-related ADRs in 4370 patients in a variety of other studies and reviewed published reports of flurbiprofen clinical trials and case reports. These reviews showed no additional, unanticipated patterns of intolerance. These clinical safety data indicate that in the doses studied, flurbiprofen is a well tolerated agent for patients requiring nonsteroidal antiinflammatory drug therapy.

Adult

Profile of ragweed hay fever symptom control with terfenadine started before or after symptoms are established.

Forty-two ragweed hay fever patients participated in a study which examined the profile of symptom relief provided by terfenadine, and the relative adequacy of symptom control with the drug given from the beginning of the season compared with treatment started after symptoms were well established. Compared with placebo, terfenadine effectively relieved sneeze, itch and eye symptoms. It had no effect on running, blowing and drainage. Subjectively perceived congestion benefited marginally. When the drug was begun after symptoms were well established, sneezing responded quickly and maximally. Eye discomfort lessened but not to the level experienced by those dosed from the beginning of the season. The pattern in other symptom categories was less clear. Overall, terfenadine improved all rhinitis symptoms except those related to hypersecretion. Some symptoms appeared to respond better when drug dosing commenced at the beginning of the season.

Adult

Hay fever treatment with combined antihistamine and cyclooxygenase-inhibiting drugs.

Twenty-eight ragweed-allergic patients with hay fever participated in a clinical trial that examined the pattern of symptom relief resulting from addition of a cyclooxygenase-inhibiting drug to standard antihistamine therapy. In the first week antihistamine use by the subjects was standardized, and subjects were oriented to use of the hay fever symptom diary. They were then allocated, according to symptom severity, to two treatment groups. One group received 120 mg of terfenadine and 300 mg of flurbiprofen (a cyclooxygenase-inhibiting drug) per day. Members of the other group received terfenadine and a placebo that looked like flurbiprofen. This treatment lasted 1 week. Subjects recorded severity of congestion, drainage, running, nose blowing, itching, and sneezing four times each day. The flurbiprofen-treated patients experienced less severe symptoms, demonstrating maximum benefit 3 to 5 days into the drug trial with some loss of effect thereafter. Secretion-related symptoms appeared to benefit most. Combined blockade of histamine and cyclooxygenase products appears to offer improved symptom control in ragweed hay fever.

Adult

Nasal airway response to infused phenylephrine in normals and in patients with allergic and non-allergic rhinitis.

To find whether patients with chronic rhinitis might be congested because of hyporesponsiveness to adrenergic vasoconstrictive influences, we measured nasal airway resistance (NAR) in normals and allergic and non-allergic rhinitics during intravenous infusion of graded doses of phenylephrine. All responded with decreases in NAR and first evidences of NAR fall appeared no later in those with rhinitis than in normals. Nasal congestion and response were asymmetrical; absolute NAR in the low resistance side was similar in all groups and there was little response to phenylephrine. In the high resistance side, NAR reached its minimum by the time the total infused dose was 1400 mcg, indicating maximum response to drug was achieved within the dose range studied. Minimum NAR achieved on the high resistance side was higher in rhinitics suggesting residual vascular engorgement resistant to phenylephrine or non-vascular mucosal swelling. Resistance to adrenergic vasoconstriction does not appear to be the primary contributor to mucosal swelling in chronic rhinitis.

Airway Resistance

Vasoconstrictor and corticosteroid responsive components of allergic nasal mucosal swelling.

This study evaluated the relative contributions of vascular engorgement and less reversible components of inflammation (edema, cellular infiltration) to production of allergic nasal congestion. We established the minimum nasal airway resistance (NAR) inducible by oxymetazoline spray in 29 asymptomatic patients. During ragweed season, we restudied them with the same decongestant regimen before and after 1 week of treatment with oral methylprednisolone (Medrol tablets, Upjohn) or a matched placebo. It was not possible, in the conditions of this study, to decongest symptomatic patients to baseline using only the topical vasoconstrictor. This could be accomplished in those receiving methylprednisolone. Corticoid therapy relieved a non-vascular component of congestion or rendered vasoconstrictor therapy more effective.

Adrenal Cortex Hormones

Effect of intranasal histamine on nasal mucosal blood flow and the antidiuretic activity of desmopressin.

The effects of exogenous histamine on nasal mucosal blood flow and the systemic activity of intranasally administered desmopressin, a vasopressin analogue, were studied in normal volunteers. Ten subjects received either saline or histamine (1, 20, 100, and 500 micrograms) by intranasal spray. Maximal nasal mucosal blood flow response, determined by laser doppler velocimetry, demonstrated a significant (P less than 0.05) linear relationship to histamine dose. Eight additional subjects received each of the following intranasal treatments: 20 micrograms histamine followed by 10 micrograms desmopressin; normal saline followed by 10 micrograms desmopressin; 20 micrograms histamine followed by vehicle; or normal saline and vehicle. Nasal blood flow was determined before and after each treatment. Desmopressin activity was assessed by measuring urine osmolality, flow rate, electrolyte, and creatinine concentration for 24 h after each treatment. The effect of histamine and desmopressin was greater than desmopressin alone, with respect to nasal blood flow response (103 +/- 24 vs. 4 +/- 17%, mean +/- SEM, P less than 0.02), initial urine osmolality (520 +/- 123 vs. 333 +/- 75 mosM, P less than 0.03), urine electrolyte (potassium, 45 +/- 11 vs. 28 +/- 7 meq/liter; sodium, 68 +/- 21 vs. 36 +/- 8 meq/liter, P less than 0.03) and creatinine concentrations (95 +/- 23 vs. 60 +/- 13 mg/dl, P less than 0.03), and the duration of decrease in urine flow rate compared with saline and vehicle. These results suggest that the systemic activity of intranasal desmopressin is enhanced by increasing local nasal blood flow and are consistent with increased transnasal absorption of the peptide.

Administration, Intranasal

Pharmacokinetics of flurbiprofen.

Both radiolabeled and nonlabeled drug have been used to study the pharmacokinetics of flurbiprofen (Ansaid, Upjohn). Drug absorption is rapid, drug disappearance half-life is independent of oral dose, and the area under the plasma drug concentration versus time curve increases with increasing oral dose. Elimination of intact drug from the peripheral circulation is biphasic and rapid. Following a single oral dose of 100 mg of flurbiprofen, drug bioavailability is equivalent using regimens of four 25-mg tablets, two 50-mg tablets, or one 100-mg tablet once daily. Long-term administration of flurbiprofen appears neither to inhibit nor induce the drug's metabolism.

Aspirin

Attenuation of protection with repeated cromolyn dosing before exercise challenge in subjects with asthma.

Though cromolyn sodium exhibits tachyphylaxis in laboratory models of allergy, this pattern has not been identified in clinical use or in human asthma provocation models. We looked for it using a treadmill exercise challenge scheme that had previously confirmed cromolyn's protective effect. Twelve exercise-sensitive asthmatic volunteers received in random order, 12 20-mg cromolyn inhalations, 12 placebo inhalations, and 11 placebo inhalations with a final 20-mg dose of cromolyn. Each regimen was given over a three-day period, with the final dose administered 30 minutes before exercise. Subjects' respiratory functions were measured before and repeatedly after exercise with body plethysmography and peak flow rates. Beginning six minutes after the end of exercise, parameters measured after single-dose cromolyn and placebo administration differed in all endpoints at most of the measurement intervals. Results with 12-dose cromolyn pretreatment were significantly different from those seen with placebo only at 40 minutes after exercise, whereas single- and multiple-dose cromolyn results differed at 20 and 30 minutes. Cromolyn accelerated recovery from exercise-induced falls in lung function; this effect was attenuated with multiple dosing. These results are consistent with development of tachyphylaxis.

Aged

Treatment of ragweed hay fever with flurbiprofen, a cyclooxygenase-inhibiting drug.

Sixty-two volunteer hay fever patients participated in a 2-week trial which examined the protective effect of the cyclooxygenase-inhibiting drug flurbiprofen. The drug suppressed symptom severity significantly, though it was not as protective as the antihistamine also employed in the trial. Flurbiprofen's effects suggests that prostaglandin release may contribute to the symptoms of allergic rhinitis.

Adolescent

Ibuprofen in osteoarthritis.

In a double-blind, multiclinic study, 437 patients with osteoarthritis were treated sequentially with ibuprofen, 1,800 mg/day, and placebo, or with aspirin, 3,600 mg/day, and placebo. Each treatment was given for four weeks. Considering relief of pain, ability to function, and general well-being, the patients preferred drug to placebo, usually by a statistically significant margin. Combined results showed no significant differences between ibuprofen and aspirin. Patients' evaluations of exercise-related pain, ability to perform a selected activity, and total discomfort and disability, and physicians' evaluations of discomfort and disability, all favored drug over placebo, and the differences were significant for a number of endpoints. The results indicated ibuprofen, 1,800 mg/day, offers about the same antiarthritic benefit as aspirin, 3,600 mg/day. Both drugs are superior to placebo. The incidence of gastrointestinal complaints with ibuprofen was similar to that with placebo and significantly lower than that with aspirin.

Activities of Daily Living

Ibuprofen or aspirin in rheumatoid arthritis therapy.

Ibuprofen is a nonsteroidal drug with analgesic, antipyretic, and anti-inflammatory properties that was recently introduced for use in antiarthritis therapy in the United States. In a year-long double-blind multiclinic trial in 885 patients with rheumatoid arthritis, ibuprofen was at least as satisfactory as aspirin, considering both efficacy and tolerance. In the majority of patients, daily doses ranged from 800 to 1,600 mg of ibuprofen and 3 to 6 gm of aspirin. The drugs did not differ greatly in providing relief from arthritis symptoms, but ibuprofen was definitely better tolerated, especially in regard to gastrointestinal complaints. Seven percent of the ibuprofen group dropped out of the study because of adverse reactions, as compared with 16% of the aspirin group; 17% of the ibuprofen group and 31% of the aspirin group had gastrointestinal symptoms.

Aged

Ibuprofen and visual function. Prospective evaluation.

Eye evaluations before and after 24 weeks of treatment with either ibuprofen (Motrin) or aspirin did not show eye toxicity with either drug in a double-blind study of 78 patients with osteoarthritis. The possibility of eye complications resulting from ibuprofen therapy suggested in two earlier reports has not been confirmed in clinical usage in other countries or in clinical trials in the United States.

Adult