Meningitis of otitic origin

The use of saliva as an indirect, non-invasive method of theophylline plasma level measurement was evaluated in 23 older men with chronic obstructive pulmonary disease and numerous concurrent medical problems. Simultaneously collected plasma and saliva samples were obtained on two or more occasions and analyzed for theophylline concentration by the Schack and Waxler spectrophotometric method. The mean (+/- SD) plasma:saliva ratio for 84 sample sets was 1.6 (+/- 0.5) with the saliva concentration averaging 64.8% (+/- 20.8%) of the plasma concentration. Multiplying a randomly chosen plasma:saliva ratio from each patient by the saliva concentration of a second randomly selected observation resulted in a predicted plasma concentration that differed by more than 20% of the measured concentrations for 16 of the 23 patients. Thus, use of saliva theophylline measurements obtained by the Schack and Waxler method to adjust dosage regimens cannot be recommended in these patients.     

Procedure for the determination of eight cholesterol oxides in poultry meat using on-column and solvent venting capillary gas chromatography

A procedure for the determination of eight relevant cholesterol oxides in poultry meat has been developed. The method consists of the enrichment of cholesterol oxides by means of the combined use of solid-phase fractionation and thin-layer chromatography. Florisil and silica columns of 10 g permitted the handling of the total cholesterol oxides content included in the lipid bulk obtained after the Folch's extraction of 20 g of muscle meat. The determination of cholesterol oxides under their trimethylsilyl derivatives was performed by using capillary gas chromatography. The use of a fused-silica open tubular capillary column 30 m x 0.25 mm I.D. coated with 5% phenylmethylsilicone and with a film width of 0.25 micron permitted the separation of all the species. Two modes of injection (on-column and solvent venting) were evaluated and compared for the analysis of cholesterol oxides. On-column capillary gas chromatography (cGC) gave better absolute areas relative standard deviation (R.S.D.) values: 3% to 6% vs. 5% to 7% for solvent venting cGC. Regression analysis for each cholesterol oxide was performed for the two modes of injection. The possibility of large volume injection (10 microliters) by using the solvent venting mode was also evaluated in order to increase the sensitivity of the detection of cholesterol oxides. R.S.D. values for absolute areas ranging from 6% to 14% were obtained. The validation of the method was carried out within the range of 0.1-1 ppm. Absolute and relative recovery values ranging from 80% to 100% were obtained. Statistical analysis revealed that the method was reproducible. cGC-mass spectrometry was also used to confirm the peaks detected by cGC: the total ion chromatogram mode was used for the analysis of samples containing concentrations down to 0.1 ppm of cholesterol oxides. The analysis of fresh and cooked chicken meat revealed the presence of cholesterol oxides proceeding from the autoxidation of the cholesterol B-ring. Finally, saponification was found to be not as accurate as the described procedure for cholesterol oxides analysis.     

High-pressure liquid chromatographic and spectrophotometric assays for theophylline in biological fluids

The analysis of theophylline and other xanthine derivatives in biological fluids was examined by high-pressure liquid chromatography (HPLC) and spectrophotometric (Schack and Waxler) methods. An HPLC analysis technique involving precipitation of serum proteins using trichloroacetic acid, injection of the supernatant onto a strong cation exchange column and detection using ultraviolet absorbance provides a nonpolluting, micronized, rapid and reasonably sensitive and specific method for measuring serum theophylline concentrations during clinical pharmacokinetic monitoring. Pre-extration of xanthines with chloroform increases the sensitivity and specificity of the assay. Good agreement was found in the assay results between the spectrophotometric and HPLC assays in 23 of 25 patient specimens, but occasional severe interferences were found with the former technique.     

More sensitive high-pressure liquid-chromatographic determiantion of theophylline in serum

We present procedures for determining theophylline in 50 mul of serum. The drug is extracted into a small volume of solvent that contains an internal standard, 8-chlorotheophylline. The extract is Analyzed by isocratic reversedphase chromatography, with measurement of eluted theophylline at 273 nm. Day-to-day reproducibility within 5% is attainable for the concentration range 5--20 mg/liter. Other xanthines and related metabolites do not interfere. Sensitivity is 1 mg/liter. The correlation coefficient, when results by a spectrophotometric procedure were compared, was 0.989. Amobarbital, secobarbital, phenobarbital, and diphenylhydantoin do not interfere. Total analysis time for a single sample is 15 min.     

Mitochondrial DNA mutations in multiple symmetric lipomatosis

We describe an analytical technique for measuring residues of imidacloprid, a relatively new and highly active insecticide, in water and soil using high-performance liquid chromatography (HPLC). All analyses were performed on reversed-phase HPLC with UV detection at 270 nm using a mobile phase of acetonitrile-water (20:80, v/v). Fortified water samples were extracted with either solid-phase extraction (SPE) or liquid-liquid extraction methods. A detection limit of 0.5 microgram/l was achieved using the SPE method. The imidacloprid residues in soils were extracted with acetonitrile-water (80:20, v/v), and the extract was then evaporated using a rotary evaporator. The concentrated extract was redissolved in 1 ml of acetonitrile-water (20:80, v/v) prior to analysis by reversed-phase HPLC. A detection limit of 5 micrograms/kg was obtained by this method which is suitable for analysis of environmental samples. Accuracy and precision at 10 and 25 micrograms/kg soil samples were 85 +/- 6% and 82 +/- 4%, respectively.     

Neurophysiological and anatomical variability of the greater auricular nerve

Micro-porous ethylcellulose (EC) membrane capsules were prepared by dissolving polyvinylalcohol (PVA) particles from membranes which were made of a mixture of EC (a water-insoluble polymer). The pore size was approximately 400 microns. Since the dissolution rate of theophylline from the micro-porous EC membrane capsules was fast, gel-forming polymer, poly(acyclic) acid (Carbomer), was incorporated inside the capsule at 10, 20 or 30 mg. Using test capsules containing 100 microns of theophylline, in vitro dissolution studies were performed. By including Carbomer in capsule formulations, the dissolution rate of theophylline was decreased. However, there were not significant differences in dissolution rates between preparations containing the three different amounts of Carbomer. In vivo evaluation studies using beagle dogs showed that AUC, Cmax and Tmax were inversely proportional to the formulated amount of Carbomer. The capsule containing 20 mg of Carbomer gave plasma theophylline concentrations between 5 and 15 micrograms mL-1, which reflect levels within the therapeutic window. The effect of food intake on the pharmacokinetics of theophylline was also studied with the same capsule. Food increased AUC, Cmax and Tmax, although plasma theophylline levels were maintained within the therapeutic range.     

Determination of 5-aminolaevulinic acid dehydratase activity in erythrocytes and porphobilinogen in urine by micellar electrokinetic capillary chromatography

A micellar electrokinetic capillary chromatographic (MECC) method has been developed and optimised for the separation of 5-aminolaevulinic acid (ALA) and porphobilinogen (PBG). The running buffer consisted of a mixture of 20 mM sodium phosphate and 20 mM sodium borate containing 50 mM sodium dodecyl sulphate (SDS) adjusted to pH 9.5 with 1 M NaOH. The running voltage and temperature were 20-25 kV and 30 degrees C, respectively. The MECC method for the analysis of PBG is fast and simple and is useful for the screening of PBG in the urine of patients suspected to have acute intermittent porphyria (AIP), and for the confirmation of lead exposure by measuring red-cell ALA-dehydratase (ALA-D) activity with ALA as the enzyme substrate.     

When mom's sick: changes in a mother's role and in the family after her diagnosis of cancer

OBJECTIVES: The objectives of this study were to compare the pharmacokinetic parameters of ibuprofen administered as a suspension, chewable tablet, or tablet in children with cystic fibrosis and to determine the optimal blood sampling times for measuring ibuprofen peak concentrations. STUDY DESIGN: A single oral 20 mg/kg dose of ibuprofen was administered, and blood samples were obtained at 15, 30, 45, 60, 120, 240, and 360 minutes after the dose was administered. Peak plasma concentration (Cmax ), time to peak concentration (Tmax ), and other pharmacokinetic parameters were determined and compared (analysis of variance and analysis of covariance). RESULTS: Thirty-eight children were included (22, 4, and 12 in the suspension, chewable tablet, and tablet groups, respectively). Tmax was the only parameter for which statistical differences were noted (suspension vs tablet, P 相似文献   

The relationship of the theophylline concentration in the saliva and the blood serum in patients with a broncho-obstructive syndrome

Theophylline salivary and serum concentrations (Tser and Tsal) were quantified after a single dose administration of theophylline drugs: euphylline (2.4% solution, 10 ml i.v. jet and 0.15 orally), theo-dur, retaphil, theopek, theobilong (0.3 g orally). The drugs were given to patients with broncho-obstructive syndrome. The samples were obtained within 6 and 24 hours upon administration for euphylline and other drugs, respectively. Tser and Tsal were determined at high-performance liquid chromatography. The authors revealed a linear relationship between Tser and Tsal in different time intervals. The percentage factors and formulas of Tser calculation by its Tsal values have been estimated.     

Evaluation of two dextrose-based directly compressible excipients

The objectives of this research were to evaluate the physical properties and compaction behavior of two dextrose-based directly compressed excipients. Anhydrous theophylline (10% w/w) was used as a drug model, Emdex and or Maltrin M510 (89.5% w/w) were used as diluent, and magnesium stearate (0.5% w/w) was used as lubricant. Direct compression and wet granulation methods were used for preparing the compacts. In general, the wet granulation method reduced the density of the mixture and consequently its flow rate compared to the mixture prepared only by solid-solid mixing. All formulations were compressed at four different compressional forces and at a target weight of 450 mg +/- 5%. Tablets obtained were different in physical properties and mechanical strength based on type of excipient used and methods of tablet preparation (direct compression versus wet granulation). Compacts prepared from Maltrin M510 had a longer disintegration time and slower drug release than compacts of the same composition but prepared with Emdex. Disintegration time and drug dissolution from tablets containing Maltrin M510 as diluent and prepared by wet granulation appeared to be controlled by a "gel" layer formation around the tablets and not by the tablets porosity. This study demonstrates that full characterization of excipients is needed because a different manufacturing process for the same excipients may produce differences in the pharmaceutical products.     

Adenovirus-mediated dystrophin minigene transfer improves muscle strength in adult dystrophic (MDX) mice

Tablets have been prepared at known compaction force from three types of pellets in different proportions: (1) pellets containing 80% theophylline as a model drug coated with different thicknesses of a polymer film coat, (2) pellets containing glyceryl monostearate as a deformable material, and (3) pellets containing a disintegrant. The breaking load, friability, disintegration and drug release properties were evaluated, the latter as a mean dissolution time (MDT) and its variance (VDT). The mechanism of dissolution was assessed from the value of the relative dispersion (RD) of the mean dissolution time. The possible relationship between the properties of the pellets and those of the tablets was evaluated by canonical analysis followed by multiple regression analysis. It was found that only about 51% of the tablet properties could be predicted from the properties of the pellets. The quantitative relationship between pellet properties and tablet properties was found to vary in type and level of quality. Reduction of breaking load, friability and disintegration was less predictable than that of dissolution represented as the MDT. The values of RD for the different preparations clearly identified those preparations where the film coat still retained control of the dissolution process. Such formulations contained at least 40% of soft pellets and coated pellets with at least a weight gain of 8%.     

An evaluative study of the short-term effects of once-daily, sustained-release theophylline on sleep in nocturnal asthmatics

OBJECTIVE: To examine the effects of once-daily, sustained-release theophylline on sleep patterns in nocturnal asthmatics. DESIGN: Double-blind, randomised, cross-over, placebocontrolled trial over 22 days. Seven-day period to establish therapeutic levels of theophylline (11.8 +/- 3 mg/l); 8-day cross-over period of 4 days' placebo or theophylline; 7-day baseline period. Electrophysiological sleep patterns, overnight bronchoconstriction and arterial O2 saturation monitored on nights 7, 11 and 15. SETTING: Sleep Laboratory, Medical School, University of the Witwatersrand. PATIENTS: Twelve volunteers who met the criteria for asthma, had previously used theophylline, were clinically stable and had a history of nocturnal awakenings caused by asthma were enrolled. OUTCOME MEASURES: Sleep-onset latency (SOL), within-sleep wakefulness (WSW), rapid eye movement sleep (REM), slow-wave sleep (SWS), peak expiratory flow rate (PEFR) and arterial oxygen saturation. RESULTS: SOL increased on theophylline--12 minutes (range 7-9 minutes) compared with placebo--6 minutes (range 3-11 minutes); WSW increased from 33 minutes (range 17-66 minutes) on placebo to 72 minutes (range 35-150 minutes) on theophylline. REM sleep was unaltered. SWS decreased in 10-12 patients, but this difference was not significant. Early morning PEFR was significantly better on theophylline in all study limbs. CONCLUSION: Our findings show that while once-daily, sustained-release theophylline improves bronchodilation in nocturnal asthmatics, it increases nocturnal wakefulness and decreases sleep efficiency during short-term treatment. This may, however, not be a long-term effect.     

Multiresidue determination of pesticides in apples and pears by gas chromatography-mass spectrometry

This paper describes a rapid, specific and sensitive multiresidue method for the routine analysis of several classes of pesticides used for the treatment of apples and pears, involving a rapid extraction procedure at pH 4.5 with a mixture of acetone-dichloromethane-hexane (50:20:30, v/v/v) and gas chromatography coupled to mass-selective detection, in order to achieve quantitative analysis down to their respective maximum residue limit. Extraction recoveries were between 55 and 98%. Limits of detection and limits of quantitation ranged respectively, from 0.01 to 0.05 mg/kg and from 0.02 to 0.1 mg/kg. Intra-assay relative standard deviation was less than 19% for all compounds. An excellent linearity was observed from these LOQs up to 500 mg/kg. Intermediate (inter-assay) precision and accuracy were satisfactory. The method has been applied to many fruit samples intended for commercialisation.     

Validation of a less-invasive method for measurement of serotonin synthesis rate with alpha-[11C]methyl-tryptophan

We tested in normal human subjects a less invasive method to obtain plasma input function required in the calculation of the brain serotonin synthesis rate measured with positron emission tomography (PET) and alpha-[11C]methyl-tryptophan (alpha-MTrp). The synthesis rates derived with the arterial input function were compared to those derived from venous plasma and venous sinus time-radioactivity curves obtained from dynamic PET images. Dynamic PET images were obtained for the lengths up to 90 minutes after an injection of alpha-MTrp (400 to 800 MBq). Input functions were generated from both artery and vein in three subjects, and from artery only in two subjects. Net unidirectional uptake constants of alpha-MTrp (K*; mL/g/min) were calculated in several brain regions graphically using data between 20 and 60 minutes after injection with different input functions. In the five subjects with arterial sampling, we tested two methods for correcting the input functions from the venous samples: (1) normalization to the mean exposure time at 20 minutes from arterial curve; and (2) the use of the venous sinus curve for the first 20 minutes. Venous curves coincided with the arterial ones after about 20 minutes. When the venous curves were used, there was an underestimation of the area under the curves up to 20 minutes, resulting in a 5% to 30% overestimation of K* values. Combined use of the sinus curve up to 20 minutes and venous curve from 20 to 60 minutes as an input function resulted in the K* (mL/g/min) values larger by 7.1 +/- 3.8% than the K* values estimated with the arterial input function. Normalization of the venous curve to the exposure time at 20 minutes obtained from the arterial plasma curve resulted in a bias in the K* of about -0.34 +/- 3.32%. The bias from the K* values was propagated to the serotonin synthesis rates. The use of a combination of the venous blood samples and venous sinus as the input function resulted in an acceptable bias in the serotonin synthesis rates from the tissue time-radioactivity curves generated by PET.     

Determination of avermectins in plasma at nanogram levels using high-performance liquid chromatography with fluorescence detection

An analytical method is described for the determination of the avermectins in plasma based upon high-performance liquid chromatography of fluorescent derivatives of these compounds. The analyte is isolated by adsorption chromatography on Florisil, dehydrated in an acetic anhydride-pyridine mixture, and the fluorophore is further separated by chromatography on silica gel in advance of introduction into a reversed-phase system. This method, which can be applied to samples containing as little as 0.2 ng drug per ml, has an accuracy of 5% mean relative error and a precision of 8% relative standard deviation. A study and discussion of several factors which affect the analytical reaction are included.     

Amino acid analysis by gas-liquid chromatography of N-heptafluorobutyryl isobutyl esters. Complete resolution using a support-coated open-tubular capillary column

Amino acids have been separated by gas-liquid chromatography as their N-heptafluorobutyryl isobutyl esters. Complete resolution of derivatives of all the common amino acids has been achieved using a high-performance support-coated open-tubular capillary column. The analysis time was 30 min. Modifications to the derivatization procedure of MacKenzie and Tenaschuk have been introduced. Acylation by heating at 150 degrees was shown to be destructive; 110 degrees has been selected for routine preparation. To obtain a volatile histidine derivative it has been found necessary to add an antioxidant and to heat samples with ethoxyformic anhydride prior to injection. Amino acid analysis of beta-lactoglobulin after 6 N HCl digestion yielded results in good agreement with those obtained by the conventional ion-exchange method. The method has also been successfully applied to estimation of the different caseins in whole casein and in purified fractions by amino acid analysis of residues liberated by carboxy-peptidase digestion.     

Determination of free bile acids in pharmaceuticals by thin layer chromatography and high performance liquid chromatography

High-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) and thin layer chromatography with flame ionization detection (TLC-FID) have been applied to the separation of five main free bile acids present in humans: cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA) and ursodeoxycholic (UDCA) acid. HPLC separation was performed on Biospher Si 100 column using a mixture of n-heptane, isopropanol, ethylacetate, methanol and glacial acetic acid as a mobile phase. All the compounds were separated in less than 12 minutes by using a gradient elution mode. TLC-FID separation was performed on S-II Chromarods with a mixture of isooctane, ethylacetate and glacial acetic acid as a mobile phase. HPLC-ELSD method was applied to the determination of CDCA and UDCA in pharmaceuticals and their purity control when LCA, DCA and CA were considered as impurities.     

Separation from related compounds and assay of calcipotriol by high-performance liquid chromatography

In this paper, two methods are presented. One involves the separation of calcipotriol, a new synthetic analogue, from two related compounds, specifically cholecalciferol (Vitamin D3) and calcitriol (1,25-dihydroxyvitamin D3). The other involves the isolation and assay of calcipotriol from a topical ointment. The study was performed with reversed-phase high-performance liquid chromatography using an RP18 column and ultraviolet detection. Applying the method of Snyder, a mobile phase mixture containing methanol-acetonitrile-water (67:23:10, v/v) was found which achieved a total separation within 18 min. A mobile phase of methanol-water (80:20, v/v) attained a slower elution of calcipotriol. For isolation and assay of calcipotriol from an ointment (Daivonex), dissolution in chloroform gave the highest recovery (> 98%). The isolation and assay process can be performed within 2 h.     

Polymorphism in anhydrous theophylline--implications on the dissolution rate of theophylline tablets

The objects of this investigation were (i) to prepare and characterize a new anhydrous theophylline phase that is metastable under ambient conditions, and (ii) to prepare model tablet formulations containing either this metastable anhydrate (I*) or stable anhydrous theophylline (I), store them under different relative humidity (RH) conditions, and compare their dissolution behavior. I* was prepared by dehydration of theophylline monohydrate (II). Variable temperature X-ray powder diffractometry of II revealed the following series of transitions: II-->I*-->I. The metastable anhydrate, I*, which has not yet been reported in the literature, appears to be related monotropically to I. It was characterized by ambient and variable temperature X-ray powder diffractometry, Karl Fischer titrimetry, and thermoanalytical techniques (differential scanning calorimetry and thermogravimetric analysis). Tablet formulations containing either I* or I were prepared and stored at 33 and 52% RH (room temperature). The solid state of the drug was monitored by X-ray powder diffractometry and the tablets were subjected to the USP dissolution test. In tablets, I* completely converted to I in < or = 10 days when stored at either 33 or 52% RH. Scanning electron microscopy provided direct visual evidence of recrystallization. This recrystallization was accompanied by a decrease in the dissolution rate of the stored formulations that was so pronounced in the formulations stored at 52% RH that they failed the USP dissolution test. The in situ solid-state transition appears to be responsible for the decrease in dissolution rate observed following storage. Stored tablets containing I showed neither a phase transition nor an alteration in their dissolution behavior.