ABSTRACT
Bimodal volcanism in the Santa Maria Province of west-central California occurred when segments of the East Pacific Rise interacted with a subduction zone along the California margin during the Early Miocene (about 17 million years ago). Isotopic compositions of neodymium and strontium as well as trace-element data indicate that these volcanic rocks were derived from a depleted-mantle (mid-ocean ridge basalt) source. After ridge-trench interactions, the depleted-mantle reservoir was juxtaposed beneath the continental margin and was erupted to form basalts. It also assimilated and partially melted local Jurassic-Cretaceous sedimentary and metasedimentary basement rocks to form rhyolites and dacites.
ABSTRACT
To examine the influence of food storage habits on the development of stomach cancer, we compared 95 patients and 190 controls selected from the general population. Information about food storage and diet was obtained from the patients and the controls by use of a questionnaire mailed to each subject followed by an interview. Low intake of salad vegetables and fruit and high intake of salt were clearly associated with stomach cancer development. No association was found with recent refrigerator use, but a halving of stomach cancer risk in subjects who had used a refrigerator for greater than or equal to 29 years persisted after allowance was made for recent diet. Risk was elevated in subjects who, when children, had lived in houses without a larder built specifically for the storage of food.
Subject(s)
Food Preservation , Stomach Neoplasms/etiology , Adult , Aged , Female , Humans , Male , Middle Aged , Refrigeration , Risk Factors , Socioeconomic Factors , Sodium, Dietary/administration & dosage , United KingdomABSTRACT
Extracts of different polarity obtained from various plant parts (root, leaf, flower and fruit) of Seseli rigidum were studied by different antioxidant assays: DPPH and ABTS radical scavenging activity, by total reducing power method as well as via total content of flavonoids and polyphenols. Essential oils of all plant parts showed weak antioxidant characteristics. The inhibitory concentration range of the tested extracts, against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus cereus, and fungi Candida albicans and Aspergillus niger was 0.01-1.50 mg/mL and of a microbicidal 0.02-3.00 mg/mL. In the interaction with cholinesterase, all essential oils proved effective as inhibitors. The highest percentage of inhibition versus human and horse cholinesterase was shown by root essential oil (38.20% and 48.30%, respectively) among oils, and root hexane extract (40.56% and 50.65% respectively). Essential oils and volatile components of all plant parts were identified by GC, GC-MS and headspace/GC-MS. Statistical analysis of the ensemble of results showed that the root essential oil composition differed significantly from essential oils of other parts of the plant. Taking into account all of the studied activities, the root hexane extract showed the best overall properties. By means of high performance liquid chromatography coupled to high resolution mass spectrometry, the 30 most abundant constituents were identified in extracts of different polarity. The presence of identified constituents was linked to observed specific biological activities, thus designating compounds potentially responsible for each exhibited activity.
Subject(s)
Anti-Infective Agents/pharmacology , Antioxidants/pharmacology , Apiaceae/chemistry , Apiaceae/metabolism , Cholinesterase Inhibitors/pharmacology , Anti-Infective Agents/chemistry , Antioxidants/chemistry , Bacteria/drug effects , Cholinesterase Inhibitors/chemistry , Cholinesterases/metabolism , Flavonoids/chemistry , Microbial Sensitivity Tests , Oils, Volatile/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Oils/chemistry , Polyphenols/chemistryABSTRACT
An infant with Ebstein's malformation of the tricuspid valve and severe pulmonic stenosis underwent a 39-day course of prostaglandin E1 infusion, and a histologic study of the ductus arteriosus was undertaken after autopsy. There were marked alterations in the ductal and juxtaductal structures following this prolonged infusion of prostaglandin E1. The internal elastic lamella of the ductus was disrupted in many areas. The media showed widespread areas of disruption with cavity formation. The adventitia adjacent to the junction of the ductus with the pulmonary artery was thickened and infiltrated with mononuclear cells. The nerve trunks in the adventitia were markedly infiltrated with mononuclear cells and showed cavitation as well as considerable surrounding edema. Mucopolysaccharides were increased throughout the ductus. These changes produced increased fragility of the ductal and juxtaductal structures, thus increasing the likelihood of spontaneous aneurysms and rupture, or of tearing or rupture at the aortic and pulmonary junctions at the time of surgical closure of the ductus. Unusual fragility of the ductus, pulmonary artery, and aorta has been observed during ligation of the ductus following prostaglandin E infusions lasting seven and ten days. Additionally, another patient who had received prostaglandin E infusion for six days demonstrated aneurysmal fullness to the ductus arteriosus at autopsy. The histologic findings and intraoperative experience in this study suggest that there may be a real danger of spontaneous or surgically related rupture of the ductus arteriosus after prolonged infusion of prostaglandins.
Subject(s)
Ductus Arteriosus, Patent/etiology , Ductus Arteriosus/cytology , Ebstein Anomaly/diagnosis , Infusions, Intra-Arterial/methods , Prostaglandins E/adverse effects , Cardiac Catheterization , Digoxin/therapeutic use , Ebstein Anomaly/drug therapy , Female , Furosemide/therapeutic use , Humans , Infant, Newborn , PregnancyABSTRACT
Two dimensional sector scan echocardiography was used to evaluate the morphologic characteristics of the surgically revised atria in 17 patients with d-transposition of the great arteries who had undergone the Mustard operation. Echocardiographic imaging of the atria was obtained from various planar projections. Dimensional measurements of various segments of the systemic and pulmonary venous atria were obtained in each patient. Correlative hemodynamic, angiographic, postmortem and echocardiographic data showed that seven patients (Group I) had no structural abnormalities of the atria. These 7 patients served as controls for 10 other patients with structural abnormalities of the surgically created atria. One patient (Group II) showed stenosis of the junction of the superior vena cava and systemic venous atrium compared with findings in the control group. Three patients (Group III) had significantly reduced echocardiographic dimensions of the junction of the anterior and posterior segments of the pulmonary venous atrium. Six patients (Group IV) had increased echocardiographic dimensions of all components of the pulmonary venous atrium due to tricuspid regurgitation. These data show that qualitative and quantitative two dimensional sector echocardiography can reliably detect structural abnormalities of the surgically revised atria after the Mustard operation.
Subject(s)
Echocardiography , Transposition of Great Vessels/surgery , Adolescent , Child , Child, Preschool , Heart Atria , Heart Ventricles , Hemodynamics , Humans , Infant , Pulmonary Veins , Tricuspid Valve/abnormalities , Tricuspid Valve Insufficiency/diagnosis , Tricuspid Valve Insufficiency/pathology , Vena Cava, Inferior , Vena Cava, SuperiorABSTRACT
More than 1,100 patients underwent a systemic-pulmonary arterial shunt operation at the Children's Memorial Hospital, Chicago, from 1946 to 1974. Of these patients, 294 were studied to assess the presence of pulmonary vascular disease and the time of its occurrence after surgery. They were selected either because lung tissue was available for histologic grading of pulmonary vascular disease (114 patients) or because hemodynamic studies were performed after the shunt operation (180 patients). The shunts, all patent at the time of the study, ranged in duration from 1 month to 23 years. After a subclavan-pulmonary arterial shunt (75 patients) there was little evidence of advatients) pulmonary vascular disease in either histologic C2 of 25 patients) or hemodynamic (1 of 50 patients) studies. After an aortic-pulmonary arterial shunt (44 Waterston, 175 Potts) there was small likelikhood of advanced pulmonary vascular disease with a shunt duration of less than 5 years (1 of 35 histologic, 0 of 27 hemodynamic studies). With a shunt duration of more than 5 years the incidence of advanced pulmonary vascular disease increased significantly (15 of 54 histologic, 17 of 103 hemodynamic studies). A mean pulmonary arterial pressure of 50 mm Hg or greater strongly suggests the presence of advanced pulmonary vascular disease. When a systemic-pulmonary arterial shunt has provided effective palliation with decreased pulmonary pressure there is small likelihood that advanced pulmonary vascular disease will develop, even with a long shunt duration of 20 to 25 years.
Subject(s)
Aorta/surgery , Heart Defects, Congenital/surgery , Lung/blood supply , Pulmonary Artery/surgery , Subclavian Artery/surgery , Thrombosis/etiology , Child , Follow-Up Studies , Hemodynamics , Humans , Lung/pathology , Palliative Care , Thrombosis/pathology , Time FactorsABSTRACT
Negative ion electrospray-tandem mass spectrometry has been employed to study chloride adducts of saccharide molecules. Decompositions of [M + Cl]- obtained under identical low-energy collision conditions allow the approximate ranking of chloride affinities and gas-phase acidities of a series of isomeric monosaccharides. The ketohexoses are found to be more acidic than the aldohexoses. Chloride adduct decompositions are examined for a glucopyranosyl fructose and a glucopyranosyl glucose series. For each disaccharide series, the linkage position is shown to markedly influence the favored pathways of [M + Cl]- decompositions, initiated either by loss of neutral HCl to form [M - H]- and possibly leading to further (consecutive) decompositions, or by loss of M to form Cl-. Upon formation of [M - H]-, both cross-ring cleavages and glycosidic bond decompositions were observed in varying degrees for the two series of disaccharides. Remarkably, for three non-reducing polysaccharides that each contain a terminal sucrose group at the "downstream" end, chlorine-containing product ions arising from cleavage of the Glcalpha-2Fru linkage have been observed. Apart from Cl-, chlorine-containing product ions are not observed for any of the other disaccharides investigated, and they appear to be specifically diagnostic of a terminal Glcalpha-2Fru linkage. Their appearance is rationalized based upon a substantially reduced tendency for HCl loss from these non-reducing polysaccharides.
Subject(s)
Chlorides/chemistry , Oligosaccharides/chemistry , Algorithms , Carbohydrate Sequence , Disaccharides/chemistry , Molecular Sequence Data , Raffinose/chemistry , Spectrometry, Mass, Electrospray Ionization , Sucrose/chemistry , ThermodynamicsABSTRACT
Department of Chemistry, University of New Orleans, New Orleans, Louisiana, USA The effect of solvent composition on negative ion electrospray ionization (ESI) mass spectrometry was examined. The onset potentials for ES1 of a series of chlorinated solvents and methanol were found to be within the range predicted by D. P. H. Smith, based on differences in the surface tension of the solvents used. The tendency toward electric discharge decreased with increasing percent weight of chlorine in the solvent. This effect has been attributed to an increasing propensity for electron capture for more highly chlorinated solvents. Addition of the electron scavenger gas SF, was even more effective at suppressing corona discharge phenomena. In a comparison of ultimate signal intensity obtainable for a test analyte in 10% methanol, the highest signal, which was stable over the widest range of temperatures, was exhibited by chloroform compared to dichloromethane, 1,2-dichloroethane, carbon tetrachloride, and methanol (100%). Chloroform, thus, is a recommended solvent for negative ion electrospray mass spectrometry (ES/MS) when solubility is not a limiting issue. Solvent polarity was shown to exhibit a profound influence on the distribution of charge states in negative ion ES/MS. For both chlorinated and nonchlorinated organic solvents, the higher the solution dielectric constant, the more the charge-state distribution is shifted toward higher charge states. These observations build on the "electrophoretic" mechanism of droplet charging. Solvents with high solution dielectric constants are considered to be most effective at stabilizing multiply charged ions (where charge separation is greatest), and they are likely to increase the level of droplet charging. Solvents with high basicities (gas phase and solution phase) and high proton affinities, yet low dielectric constants, favor lower charge states in ES mass spectra of lipid A and cardiolipin from Escherichia coli. This indicates that gas-phase processes and solvent basicity contribute much less toward ion formation than solution-phase solvation via preferred orientation of the solvent dipole.
ABSTRACT
Twenty-seven patients (3 to 22 years) underwent the Fontan operation. Seventeen had tricuspid atresia and 10 had other complex lesions. Sixteen patients had a Glenn shunt (12 prior to, three simultaneous with, and one following the Fontan operation). One early death (3.7%) occurred in a 4 1/2-year-old child with tricuspid atresia II-C, previous pulmonary artery banding, and a closing ventricular septal defect (80 mm Hg gradient). There were two late deaths (7.4%) from Candida sepsis, after 4 and 6 months, respectively. The 24 patients who survived the Fontan operation had postoperative hospital stays of 6 to 90 days (average 18). Patients with tricuspid atresia and an established Glenn shunt (nine patients, Group I) had postoperative hospital stays of 7 to 19 days (average 9.5), and none had significant pleural or pericardial effusions. Patients with tricuspid atresia without a Glenn shunt (seven patients, Group II) had postoperative hospital stays of 6 to 60 days (average 17.5), with three having significant effusions. Of the patients with other complex lesions, all without an established Glenn shunt, five had significant effusions. Four additional major complications (two tricuspid patch disruptions with ineffective pulmonary blood flow and two complete occlusions of a valved conduit) were encountered in which the Glenn shunt proved lifesaving. We believe that an established Glenn shunt played a major role in attaining minimal postoperative hemodynamic instability, effusions, renal failure, and mortality in our patients. The Glenn shunt should be considered in patients who are less than ideal candidates for the Fontan operation.
Subject(s)
Arteriovenous Shunt, Surgical , Pulmonary Artery/surgery , Tricuspid Valve/abnormalities , Venae Cavae/surgery , Adolescent , Adult , Child , Child, Preschool , Evaluation Studies as Topic , Female , Follow-Up Studies , Heart Defects, Congenital/complications , Heart Defects, Congenital/surgery , Humans , Male , Postoperative Complications , Tricuspid Valve/surgeryABSTRACT
The field of electrospray ionization mass spectrometry is reviewed with emphasis placed upon advances in the elucidation of fundamental mechanistic aspects of the ionization process that have been reported over the past 10 years. The analytical consequences of these findings are also examined. Eight central conclusions or 'tenets' are presented, as deduced from the body of work contained in 80 references.
Subject(s)
Mass Spectrometry/methods , Proteins/chemistryABSTRACT
Lipopolysaccharides (LPS), which are endotoxins found in the cell wall of Gram-negative bacteria, are common components of organic dusts that cause or contribute to symptoms associated with organic dust diseases. The lipid A subgroup within LPS is believed to be responsible for the toxicity. Acid and base treatments, which can be effective detoxification methods, were performed on lipid A from Enterobacter agglomerans (EA), a bacterium commonly found in field cotton. Negative-ion electrospray ionization mass spectrometry was employed to characterize the post-treatment structural changes to lipid A. Acid treatment (1% acetic acid, 100 degrees C) hydrolyzed the ester side-chains of lipid A. It was found that the ester-linked palmitoyl group was the most labile to acid hydrolysis. Hydrolysis of the palmitoyl moiety conformed to pseudo-first-order chemical reaction kinetics with a rate constant for decomposition of heptacyl-lipid A from Enterobacter agglomerans of approximately 3.3 x 10(-3) min-1. An order of lability of lipid A acyl side-chains to acid hydrolysis was also deduced: R4' (palmitoyl) > R1' (myristoyl or hydroxymyristoyl) > R3 (hydroxymyristoyl at position 3) > R1 (oxymyristoyl group at position 3') > R2' (lauroyl). Base treatment (0.05 M NaOH in 95% EtOH, 65 degrees C) was shown to be more effective at cleaving ester-linked side-chains. In addition, mass spectral evidence suggests that opening of the pyranose rings of the disaccharide backbone of lipid A and/or removal of the phosphoryl groups may be occurring during base treatment. This study sheds light on mechanistic aspects of treatment procedures leading to the detoxification of endotoxins.
Subject(s)
Endotoxins/chemistry , Enterobacter/chemistry , Lipid A/chemistry , Mass Spectrometry/methods , Acids , Alkalies , Carbohydrate Conformation , Carbohydrate Sequence , Endotoxins/toxicity , Hydrogen-Ion Concentration , Hydrolysis , Kinetics , Lipid A/toxicity , Molecular Sequence Data , Molecular Structure , Myristic Acids , PalmitatesABSTRACT
The application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) to the analysis of blood serum leads to the observation of a large variety of reproducible mass spectral peaks corresponding to blood components. In this study, the use of MALDI-TOFMS was developed as a tool for monitoring immune response to bacterial infection. Employing the MALDI-TOFMS approach, the levels of many components of blood were found to be immune response independent whereas others were found to correlate directly with the response of the immune system to two known types of bacteria (Staphylococcus aureus and Enterococcus faecalis). The methodologies reported here should be useful for the rapid monitoring of blood, especially that of the immune response mechanisms in various animal species.
Subject(s)
Bacterial Infections/immunology , Blood Proteins/analysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Animals , Bacterial Infections/microbiology , Enterococcus faecalis , Gram-Positive Bacterial Infections/immunology , Mice , Mice, Nude , Staphylococcal Infections/immunologyABSTRACT
Several species of the genus Haemophilus are well known etiological agents of pneumonia, meningitis, conjunctivitis, epiglottitis and chancroid. However, identification and speciation of Haemophilus is both time consuming and labor intensive. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI/TOF-MS) has been used by several investigators to profile proteins from intact and disrupted bacteria; consequently, MALDI/TOF-MS has emerged as a powerful tool in diagnostic bacteriology. This paper reports the use of MALDI/TOF-MS as a technique for the rapid identification and speciation of Haemophilus. This technique was used to not only identify the pathogen, H. ducreyi, but also to determine strain differences from different isolates. Mass spectral 'fingerprints' were obtained which permitted the rapid speciation of not only pathogenic forms of Haemophilus, but also those bacteria which are normally regarded as non-pathogenic and members of the normal flora. MALDI/TOF mass spectra can be acquired in 10 min, allowing the identification of Haemophilus spp. within 24 h rather than the 48 h or more needed for traditional bacteriological methods. In addition, these are the first mass spectral fingerprints available in the literature for many of these organisms.
Subject(s)
Haemophilus/isolation & purification , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Aggregatibacter actinomycetemcomitans/isolation & purification , Bacterial Proteins/analysis , Bacterial Proteins/chemistry , Chancroid/diagnosis , Chancroid/microbiology , Exudates and Transudates/chemistry , Fluorescent Antibody Technique, Indirect , Haemophilus/chemistry , Haemophilus/classification , Haemophilus ducreyi/chemistry , Haemophilus ducreyi/classification , Haemophilus ducreyi/isolation & purification , Humans , Neisseria gonorrhoeae/isolation & purification , Sexually Transmitted Diseases, Bacterial/diagnosis , Sexually Transmitted Diseases, Bacterial/microbiologyABSTRACT
Eight infants with complex cardiac anomalies and pulmonary stenosis or atresia were noted to have obstructed total anomalous pulmonary venous drainage (TAPVD) either at the initial cardiac catheterization (Group 1; n = 2) or after creation of systemic-pulmonary artery shunts (Group 2; n = 6). The 2 patients in Group 1 underwent early repair of TAPVD (1 at 7 days, the other at 1 1/2 months of age) before any subsequent operation and are now doing well at 18 months of age. The 6 patients in Group 2 underwent repeat cardiac catheterization because of persistent severe cyanosis with faint or absent continuous murmur and were found to have patent shunts and obstructed TAPVD (1 mild, 5 severe). One patient who underwent repair of TAPVD at 2 1/2 months of age survived and is well at 2 years of age, whereas 4 patients who underwent repair at an average age of 6 months (age range, 3-16 months) subsequently died. The sixth patient, who did not undergo repair, remained severely cyanotic with hypoplastic pulmonary arteries in spite of repeated shunts. We feel that increased awareness of the possible association of TAPVD and reduced pulmonary blood flow in infants with complex cardiac defects, in combination with echocardiography, oxygen saturation studies, and angiography with prostaglandin E1 challenge, should lead to early diagnosis, avoidance of unnecessary systemic-pulmonary artery shunts, and increased survival rates in these infants.
Subject(s)
Heart Defects, Congenital/surgery , Pulmonary Artery/abnormalities , Pulmonary Veins/abnormalities , Constriction, Pathologic/surgery , Cyanosis/etiology , Female , Humans , Infant , Infant, Newborn , Male , Pulmonary Artery/surgery , Pulmonary Veins/surgeryABSTRACT
The rapid analysis of picomole quantities of various cationic molecules (laser dyes, tripeptides and larger bioactive peptides) has been achieved by on-line capillary electrophoresis-electrospray mass spectrometry (CE-ES-MS). Use of the cationic surfactant, cetyltrimethylammonium chloride (CTAC) in the CE buffer greatly facilitated the analyses. Under reversed-polarity conditions (negative potential at the source vial), CTAC induces electroosmotic flow towards the mass spectrometer, presumably due to the creation of a cationic layer on the inner surface of the fused-silica capillaries. CTAC diminishes analyte-capillary wall interactions, allowing efficient separations and symmetrical peak shapes. It may be used over a wide range of pH values without loss of electroosmotic flow. Added selectivity, provided by the surfactant properties of CTAC, played a critical role in resolving closely related tripeptides as well as larger (five to thirteen amino acid units) peptides. Above the critical micelle concentration of CTAC, interactions with the pseudostationary micellar phase increased selectivity even for ionic analytes.
Subject(s)
Cetrimonium Compounds/chemistry , Electrophoresis/methods , Mass Spectrometry/methods , Surface-Active Agents/chemistry , Amino Acid Sequence , Buffers , Cetrimonium , Molecular Sequence Data , Oligopeptides/analysis , Rhodamines/chemistryABSTRACT
A new type of hydrophilic derivatized capillary has been used to enable the on-line capillary electrophoresis separation and electrospray mass spectrometric detection of a mixture of proteins containing bovine cytochrome c, tuna cytochrome c and horse heart myoglobin. Less than 40 fmol of each compound were loaded into the capillary. Baseline resolution of components was achieved, as were accurate assignments of molecular masses. The hydrophilic derivatized capillaries were taken through extensive testing procedures to characterize their performance and capabilities for protein analysis. A mixture of six proteins (cytochrome c, ribonuclease A, alpha-chymotrypsinogen, myoglobin, carbonic anhydrase II and alpha-lactalbumin) in acetic acid-sodium acetate buffer was used to delineate the relationships between migration time and pH, along with migration time and buffer concentration for each protein. The variations in capillary efficiency as a function of pH and as a function of buffer concentration were also characterized for the same six proteins in the acetic acid-sodium acetate system. A pH of 4.8 was found to offer an excellent compromise between separation efficiency (up to 500,000 theoretical plates) and analysis time. Capillary efficiencies were also found to be very good when employing a Tris.HCl electrolyte adjusted to pH 4.8. Lastly, electropherogram reproducibility and capillary durability were examined with the finding that little deterioration of the capillary occurred over the course of 400 injections (200 h run time). This represents a notable improvement over previously documented derivatization procedures designed to reduce protein adsorption to fused-silica capillary walls.
Subject(s)
Electrophoresis/methods , Mass Spectrometry/methods , Proteins/analysis , Animals , Buffers , Capillary Action , Carbonic Anhydrases/analysis , Cattle , Chymotrypsinogen/analysis , Cytochrome c Group/analysis , Electrophoresis/statistics & numerical data , Horses , Hydrogen-Ion Concentration , Lactalbumin/analysis , Mass Spectrometry/statistics & numerical data , Molecular Weight , Myoglobin/analysis , Reproducibility of Results , Ribonuclease, Pancreatic/analysis , TunaABSTRACT
Amoxycillin 3 g twice daily is effective in treating patients with bronchiectasis who have daily purulent sputum. However, it is a relatively expensive treatment if used for prolonged periods. This pilot study in six patients with bronchiectasis showed that the concurrent administration of probenecid with a smaller dose of amoxycillin produced similar clinical responses and pharmacokinetic profiles to those found with high dose amoxycillin alone. The amount of amoxycillin used was reduced by two thirds, producing a potential saving of approximately pound 1000 per patient per annum in those taking long term treatment.
Subject(s)
Amoxicillin/pharmacokinetics , Bronchiectasis/drug therapy , Probenecid/pharmacology , Adult , Aged , Amoxicillin/administration & dosage , Amoxicillin/adverse effects , Amoxicillin/therapeutic use , Bronchiectasis/metabolism , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Probenecid/administration & dosage , Probenecid/adverse effectsABSTRACT
A single dose, single point method of predicting patients' oral maintenance theophylline dosage has been compared with a noninvasive method. Twenty patients with obstructive lung disease received an oral dose (6 mg kg-1) of micro-crystalline theophylline. The plasma theophylline concentration after 8-10 h was then used to calculate the optimum maintenance dose of sustained release aminophylline required to achieve steady state concentrations between 55 and 110 mumols l-1. The mean steady state plasma theophylline concentration for this dosage schedule was also predicted by a method using population average pharmacokinetic parameters (assumed clearance method). These predictions were then compared with observed concentration-time profiles at steady state. The mean difference between the observed values and those predicted from a morning test dose was -0.11 mumol l-1 (95% CI -7.0 to +7.2). A larger difference (-7.4 mumol l-1 95% CI -18.2 to +3.4) was found for the assumed clearance method. Since the confidence intervals contain zero, these differences are not significantly different from zero at the 5% level, although the morning test dose method allowed prediction of the whole concentration-time profile and was more precise. An evening test dose was also used in the study, but the mean difference between the observed values and those predicted from this method was larger at -24.8 mumol l-1 (95% CI -32.89 to -17.21) and was significantly different from zero. This study indicates that a morning test dose followed by a single blood sample can be used to establish maintenance theophylline therapy quickly and safely in selected patients.
Subject(s)
Lung Diseases, Obstructive/blood , Theophylline/pharmacokinetics , Adult , Aged , Drug Administration Schedule , Female , Humans , Lung Diseases, Obstructive/drug therapy , Male , Middle Aged , Theophylline/blood , Theophylline/therapeutic use , Time FactorsABSTRACT
In biological matrixes lipid material often poses an interference problem for determinations of nonpolar compounds, e.g., polycyclic aromatic hydrocarbons (PAHs). A newly developed supercritical fluid extraction plus adsorbent method, "SFE-plus-C(18)", offers selective extraction of PAHs in lipid-rich biological matrixes without the need for supplementary cleanup. This method eliminates the use of large volumes of toxic solvent and lengthy lipid removal procedures. This study reports the first application of the SFE-plus-C(18) method to the analysis of a genuine food product, i.e., smoked meat (beef). The procedure employs the addition of C(18) adsorbent beads to the initial sample slurry of pureed smoked meat prior to supercritical CO(2) extraction and GC/MS quantitation. During SF extraction, indigenous lipids are preferentially retained on the beads, and PAHs are selectively extracted with supercritical CO(2). In a comparison of determinations of PAHs by SFE-plus-C(18) vs the conventional SFE method, only 11-17% of the indigenous lipids observed by the conventional SFE method were co-extracted using the SFE-plus-C(18) method. The PAHs in smoked meat could thus be determined efficiently in the presence of a reduced background of co-extracted lipids. Out of 10 targeted PAHs, seven were detected with a range of 10.0-26.0 ng/g in the smoked meat sample. The other three PAHs were not present above the detection limit of the instrument (2.5-4.1 pg). The recoveries of PAHs obtained using the conventional SFE method were 63-94% lower than those achieved by SFE-plus-C(18).
Subject(s)
Chemistry Techniques, Analytical/methods , Meat/analysis , Polycyclic Aromatic Hydrocarbons/isolation & purification , Animals , Carbon Dioxide/chemistry , Cattle , Gas Chromatography-Mass Spectrometry/methods , Lipids/chemistry , Polycyclic Aromatic Hydrocarbons/analysisABSTRACT
The effect of an oral slow-release aminophylline preparation (Phyllocontin Continus tablets) in preventing early morning reduction in airway calibre was measured in two groups of asthmatic patients; Group I consisted of eight stable asthmatics whose main complaint was nocturnal wheeziness, and Group II comprised four severe asthmatics studied during the period of recovery from an acute exacerbation of asthma. In both groups the effect on one second forced expired volume (FEV1) of two 225 mg tablets of Phyllocontin was compared with that of two placebo tablets on two successive nights in a double-blind trial. On the nights when the placebo preparation was administered both groups of patients showed a marked fall in FEV1. Administration of the active aminophylline preparation prevented this reduction in airway calibre in the Group I patients but had no effect on the fall in FEV1 in the Group II patients. A possible explanation for the observed difference in response between the two groups may have been variation in bioavailability of aminophylline in the two clinical situations.