The potential clinical utility of serum alpha-protryptase levels.

BACKGROUND: Because biopsy criteria for diagnosing systemic mastocytosis are not precise, the value of serum alpha-protryptase levels in the work-up of suspected systemic mastocytosis should be considered. OBJECTIVE: A retrospective analysis was performed on subjects with total tryptase serum levels that were high (>/=20 ng/mL), while beta-tryptase serum levels were normal (<1 ng/mL) or modestly elevated (1 to 5 ng/mL). METHODS: Over a 3.5-year period, 52 qualifying specimens were identified from 1369 consecutive samples. The corresponding subjects were divided into those with suspected mastocytosis and those with suspected anaphylaxis. Subjects with suspected mastocytosis were subdivided into 3 subgroups on the basis of biopsy results (positive, negative, or not available). Subjects with suspected anaphylaxis were subdivided into living and deceased subgroups. RESULTS: Among the 15 subjects who underwent biopsy, alpha-protryptase serum levels (the difference between directly-measured levels of serum total tryptase and beta-tryptase), when greater than 75 ng/mL (n = 9), were always associated with a positive biopsy result for systemic mastocytosis; levels from 20 to 75 ng/mL (n = 6) were associated with a positive biopsy result in 50% of subjects. alpha-Protryptase serum levels may be a more sensitive screening test than a bone marrow biopsy for this disorder. Also, elevated alpha-protryptase serum levels in some adult patients return to normal over time, suggesting that mast cell hyperplasia resolved in these patients. Finally, a high alpha-protryptase level may reveal anaphylaxis to be a presenting manifestation of systemic mastocytosis or mast cell hyperplasia. CONCLUSION: Levels of serum alpha-protryptase, relative to those of beta-tryptase, appear to be useful in the diagnostic work-up and follow-up of subjects with suspected systemic mastocytosis.

Comparative study of the pharmacokinetic characteristics of slow release theophylline oral preparations in Thai children with persistent asthma.

Significant differences in the rate and extent of absorption exist between slow release theophylline (SRT) preparations. The pharmacokinetic characteristics of Xanthium were compared with those of Theo-Dur in twelve Thai children with stable persistent asthma by randomized, double blind, crossover study. Serum theophylline concentrations (STCs) were determined by fluorescence polarization immunoassay. The pharmacokinetic parameters were estimated by using a computer program (Topfit 2.0). The STCs, at steady state after different doses, were predicted by using the modified Wagner-Nelson Equation. The mean resident time (MRT) and apparent T1/2 were significantly larger for Xanthium, but the Cmax and AUC0-infinity of Xanthium were significantly lower than those of Theo-Dur. The Frel of Xanthium was 80.1% relative to Theo-Dur. The appropriate dosing interval of both preparations for Thai children was twice a day.

Gentamicin pharmacokinetics in Thai neonates: recommendation for a dosing guideline.

A pharmacokinetic study of gentamicin was performed on 32 Thai neonates. After a single intravenous infusion of gentamicin at 2.5 mg/kg body weight, blood samples were collected at 0.5 and 12 hours. Serum gentamicin concentrations were determined with use of fluorescence polarizing immunoassay. None of the neonates with < 28 weeks post conceptional age (PCA), contrary to most of the more mature neonates, achieved the recommended therapeutic peak concentrations. The volume of distribution (Vd) and elimination half-life (T1/2) of gentamicin were found to reversely correlate with the PCA, with significantly larger Vd and longer T1/2 values observed among the premature neonates. Our findings were similar the results previously reported in Caucasians, and thus strongly indicated the necessity of gentamicin dosage adjustment among Thai neonates according to their PCA. A gentamicin dosing guideline for Thai neonates has been proposed, nonetheless, with higher doses and longer dosing intervals recommended among premature neonates.

Skin prick reaction and nasal provocation response in diagnosis of nasal allergy to the house dust mite.

BACKGROUND: The allergen skin test is commonly used to ensure the diagnosis of allergic rhinitis even though positive results do not necessarily indicate that rhinitis is of allergic origin. OBJECTIVE: To determine the association between skin prick reactions and nasal provocation responses to Dermatophagoides pteronyssinus (Der p) allergen extract. METHODS: Twenty-six patients with perennial rhinitis and 25 controls underwent skin prick and nasal provocation tests to standardized Der p allergen extract. With the use of allergen extract titration delivered by a metered dose pump, nasal stuffiness, itching, and sneezing were noted, the amount of secretions measured, and nasal airway resistance was recorded by active anterior rhinomanometry. RESULTS: The majority of the patients with rhinitis (20/26), but none of the controls, exhibited strong skin test positivity (4+) to Der p allergen extract. In addition, the majority of the patients with 4+ skin reactions (16/20) had moderate to severe rhinitis. Significantly increased nasal reactivity to the allergen was also observed among those with 4+ skin test positivity. The controls exhibited nasal provocation responses only with significantly higher end-point doses of the allergen extract regardless of the skin test results. CONCLUSION: Only 4+ skin test positivity was closely associated with increased nasal reactivity to Der p allergen among the patients with perennial rhinitis. The nasal provocation technique would be a useful adjunct testing to ensure the diagnosis of nasal allergy to the Der p mite, particularly among those patients with rhinitis with only mild to moderate skin test positivity.

Evaluation of threshold criteria for the nasal histamine challenge test in perennial allergic rhinitis.

Nasal reactivity to histamine was determined in patients with perennial allergic rhinitis and in control subjects. A histamine titration method delivered by a metered dose pump was used. Stuffiness, itching, and the number of sneezes were recorded, nasal secretions measured, and nasal airway resistance was recorded by active anterior rhinomanometry. Increased nasal reactivity to histamine was observed among rhinitic patients and inversely correlated with the severity of nasal symptoms. A 3-fold increase of post-saline nasal airway resistance (NAR) best differentiated the nasal responses to histamine in rhinitic patients from those in control subjects. A histamine dose of < or = 2.5 microg provoked a 3-fold increase in NAR, strongly suggesting moderate or severe symptomatic rhinitis in most cases. Nasal provocation techniques might be a useful tool for objectively assessing disease severity and response to treatment in perennial allergic rhinitis.

A single-dose comparison of three slow-release theophylline oral preparations in healthy Thai volunteers.

The study was done to compare the pharmacokinetic characteristics of three slow-release theophylline (SRT) preparations. Twelve healthy nonsmokers were randomly assigned a single dose of the following treatments at weekly intervals: Theo-Dur, Theo-24 or Xanthium orally, or aminophylline intravenously. Serially collected serum samples were analyzed for theophylline with use of fluorescence polarization immunoassay (FPIA). All three SRT preparations showed reliable absorption characteristics, but Theo-Dur had a shorter Tmax and MRT and a higher Ka. The pharmacokinetic characteristics of Theo-24 and Xanthium were similar except that Xanthium had lower bioavailability. Using single dose data for simulation of steady state pharmacokinetics, we found that a once-a-day dosage regimen with either Theo-24 or Xanthium would maintain serum levels within the therapeutic range for average non-smoking young adults whereas more frequent dosing intervals with Theo-Dur would be more appropriate. Our results argue against open substitution of SRT preparations without, close monitoring of the serum theophylline concentrations when a change is made.

Bioequivalence of a generic slow-release theophylline tablet in children.

OBJECTIVE: To determine whether a generic slow-release theophylline tablet (manufactured by Sidmak Laboratories, Inc.) is therapeutically equivalent to a proprietary theophylline tablet, Theo-Dur, in children. DESIGN: Prospective, randomized, double-blind, crossover trial. SETTING: Multicenter clinics. PATIENTS: 38 children, 6 to 16 years of age, with asthma. INTERVENTIONS: Individualized doses of Theo-Dur or generic tablet every 12 hours for 5 days. MEASUREMENTS AND MAIN RESULTS: During the last 24 hours of each regimen, theophylline serum concentrations were measured serially and a standardized exercise stress test was performed at 24 hours (trough serum concentration). Neither formulation effectively blocked the response to exercise; the maximum decrease in forced expiratory volume in the first second was 26.1% +/- 18.9% with Theo-Dur and 24.8% +/- 19.7% with the generic product (p = 0.68; beta = 0.08). The mean +/- SD peak serum concentrations were 18.0 +/- 3.0 micrograms/ml with Theo-Dur and 18.7 +/- 3.7 micrograms/ml with the generic tablet; the trough serum concentration was < 10 micrograms/ml in 15 subjects after administration of Theo-Dur and in 20 subjects after administration of the generic product. There were no significant differences in relative extent of absorption or the time to reach peak serum concentration. CONCLUSIONS: This generic formulation and Theo-Dur are bioequivalent in children. However, these results cannot be extrapolated to slow-release theophylline formulations that have not been approved by the U.S. Food and Drug Administration as equivalent to Theo-Dur.