First-line bevacizumab combined with reduced dose interferon-alpha2a is active in patients with metastatic renal cell carcinoma.

BACKGROUND: In patients with untreated metastatic renal cell carcinoma (mRCC), progression-free survival (PFS) was longer with bevacizumab + interferon (IFN)-alpha than IFN + placebo (AVOREN trial). In this hypothesis-generating study, subgroup analysis was carried out to determine the effect of IFN dose reduction. PATIENTS AND METHODS: A total of 649 patients received IFN 9 MIU s.c. three times weekly plus bevacizumab 10 mg/kg or placebo every 2 weeks until disease progression. The IFN dose was reduced to 6 or 3 MIU with the development of IFN-attributed toxicity. Differences between treatment arms in PFS, response rate and tolerability were analysed in the reduced-dose group. RESULTS: IFN dose was reduced in 131 patients in the bevacizumab + IFN arm and 97 patients in the IFN + placebo arm during the trial. PFS rates in the bevacizumab + reduced-dose IFN group were comparable with the total population (Kaplan-Meier estimates of event-free rate at 1 year: 0.524 versus 0.427). Bevacizumab + reduced-dose IFN was well tolerated, with substantial decreases in the rate of adverse events following dose reduction. CONCLUSION: This retrospective subgroup analysis suggests that the dose of IFN can be reduced to manage side-effects while maintaining efficacy in patients with mRCC receiving bevacizumab + IFN.

The bioavailability of injectable, amorphous form of aztreonam.

Amorphos injectable form of aztreonam (BIOKTAM) was prepared. It was shown that after intramuscular or intravenous administration there are not any considerable differences in the bioavailability of aztreonam from BIOKTAM and of the drug from AZACTAM.

Identification and quantitation of source from hemoglobin of blood and blood mixtures by high performance liquid chromatography.

The described technique offers a sensitive and reproducible method for inferring the source of over 50 different animal species from bloodstains and blood mixtures. Hemoglobins from each of the species were examined using reversed-phase high performance liquid chromatography (HPLC) in chromatographic times of less than 25 mins. The HPLC method complements and furthers current methodology for identification of species of origin. HPLC analysis is particularly well suited for the quantitative analysis of blood and blood mixtures and is applicable to species for which antisera are unavailable. The sensitivity of the method (hemoglobin amounts down to 1.2 micrograms) lends itself to the analysis of blood mixtures in which only a small percentage of the mixture represents blood from a given species. Such resolution and quantitation is applicable to wildlife forensic casework.

Simultaneous determination of mexiletine and four hydroxylated metabolites in human serum by high-performance liquid chromatography and its application to pharmacokinetic studies.

A high-performance liquid chromatographic method has been developed for the simultaneous determination of mexiletine and its four hydroxylated metabolites in human serum. The method involves a single-step extraction of mexiletine, hydroxymethylmexiletine, p-hydroxymexiletine and their corresponding alcohols with diisopropyl ether-dichloromethane-propan-2-ol (2.5:1.5:0.5, v/v). Separation of the compounds on a deactivated Supelcosil LC8-DB column is accomplished by high-performance liquid chromatography with ultraviolet detection at 203 nm. Overall the recovery of each compound is reproducible and greater than 75%. The lower limit of detection is 2 ng/ml for mexiletine and its metabolites. The application of the method is shown by measuring the concentrations in serum of mexiletine and its metabolites over 24 h in a healthy volunteer after a single intravenous injection of the drug and by monitoring serum concentrations in patients receiving long-term treatment by mouth of the drug.

Prazosin concentration monitoring in the treatment of prostatic adenoma.

In a prospective study of 32 patients with BPH treated with Minipress (prazosin), determinations of drug plasma levels were carried out. The comparison of clinical results and serum plasma levels enabled optimalization of the dosage in long-term therapy.

Role of nasal allergy in chronic maxillary sinusitis--diagnostic value of nasal challenge with allergen.

The role of nasal allergy in chronic maxillary sinusitis without an air-fluid level was studied in 37 patients. Seventy-three nasal provocation tests with various inhalant allergens were performed in 37 patients by means of rhinomanometry, and maxillary sinus radiographs were performed before and repeatedly after the allergen challenge. Forty-one positive nasal responses (NRs) occurred in 29 patients; 13 were immediate only, 18 were late only, and 10 NRs were dual responses. Of these responses, 32 demonstrated radiographic changes, primarily an increase in mucosal edema and/or opacification. These responses were accompanied by increased pressure in the maxillary sinuses, acute headache, and sometimes otalgia. Eight patients did not develop any NRs; however, increased thickening of the mucosal membrane of the maxillary sinuses, accompanied by subjective symptoms, was recorded in three of these nonresponders. These results demonstrate the role of nasal allergy in some patients with chronic maxillary sinusitis, which may affect the diagnostic and therapeutic approaches to this disorder.

Pharmacokinetics of mexiletine and its metabolites, hydroxymethylmexiletine and p-hydroxymexiletine, after single oral administration in healthy subjects.

Pharmacokinetics of mexiletine and its major metabolites, p-hydroxymexiletine and hydroxymethylmexiletine, were studied in 10 healthy subjects after administration of a single oral 400 mg dose. Mexiletine was extensively metabolized to hydroxymethylmexiletine and less to p-hydroxymexiletine. Mean metabolic ratio (Rm) was 0.54 and 0.18 respectively. Peak serum concentrations (Cmax) for mexiletine (0.686 +/- 0.110 micrograms/ml), hydroxymethylmexiletine (0.507 +/- 0.087 micrograms/ml), and p-hydroxymexiletine (0.096 +/- 0.046 micrograms/ml) occurred after 3.0, 4.0 and 4.2 +/- 0.6 h. Disposition parameters for mexiletine were as follows: volume of distribution (V lambda), 5.44 +/- 1.44 l/kg; serum clearance (CL) 8.08 +/- 1.23 ml/min/kg. There were no significant differences in elimination half-life (t1/2) and mean residence time (MRT) for mexiletine and its metabolites. Double-peak phenomenon was observed for all the subjects on elimination phase of mexiletine, hydroxymethylmexiletine and p-hydroxymexiletine.

Effects of oral cromolyn on the nasal response due to foods.

Thirty-eight patients with a perennial allergic rhinitis, who developed a nasal response to ingestion challenge with certain foods, were randomly selected for protection tests with oral cromolyn sodium (Nalcrom). The food challenges were performed in combination with rhinomanometry. The patients were pretreated with cromolyn or placebo by double-blind crossover schedule, in a daily oral dose of 200 mg (four times), starting 3 days before and continuing up to 3 days after the food ingestion challenge. The 38 patients previously developed 25 immediate, 24 late, and 6 delayed nasal responses to food ingestion challenge. Cromolyn fully prevented 15, significantly decreased 9, and was ineffective in 1 case of immediate nasal response. Of the 24 cases of late response, cromolyn fully prevented 10, significantly decreased 12, and was ineffective in 2. Of the 6 cases of delayed response, 2 cases were decreased significantly by cromolyn, while the other 4 cases were not. The protection effects of oral cromolyn were highly significant for the immediate and late nasal responses and nonsignificant for delayed responses. It can be concluded that cromolyn in a daily oral dose of 200 mg four times prevented the immediate and late nasal responses to ingested food.

A rapid HPLC method for plasma and serum mexiletine determination and its use in therapeutic drug monitoring.

A HPLC method for the determination of mexiletine in human plasma and serum is described. Serum or plasma after addition of mexiletine and internal standard was extracted with diisopropyl ether. The extract was then evaporated and dissolved in the mobile phase. An aliquot of the solution was chromatographed on a reversed-phase C8 column. The peaks were detected by UV (214 nm) at room temperature. The limit of detection of mexiletine was approximately 0.02 mg/l of plasma or serum. The validity of the method is discussed and compared with other methods.

[Enuresis and encopresis as a reaction to food]. / Enuresis en encopresis als reactie op voedingsmiddelen.

A meanwhile 10-year old girl, suffering from diurnal and nocturnal enuresis and encopresis since she was a baby, had been repeatedly examined and treated by various medical specialists and a homeopathic doctor without any significant improvement. The incontinence persisted. Finally her problem was solved after an allergological examination. The skin tests and specific IgE antibodies were positive for various foods, some of them confirmed later by food ingestion challenge. She was put on a complete elimination diet, combined with oral disodium cromoglycate, and has been free of all complaints since 1 1/2 years.

Determination of amiodarone and its metabolite desethylamiodarone in human plasma and serum.

A liquid chromatographic method for the assay of antiarrhythmic drug amiodarone and its metabolite desethylamiodarone in human plasma or serum has been developed. The method is simple and sufficiently sensitive for pharmacokinetic studies. Amiodarone, desethylamiodarone and added internal standard L 8040 were twice extracted at various pH from serum or plasma. The extract after evaporation was reconstituted in the mobile phase and chromatographed on reversed phase Hibar LiChrosorb RP-8 column with UV detection, at 254 nm. The method is specific and can detect approximately 30 ng of amiodarone and desethylamiodarone in 1 ml of plasma or serum.