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Application of simultaneous excitation/detection to generate real-time excitation profiles in fourier transform ion cyclotron resonance mass spectrometry

Simultaneous excitation/detection (SED), which permits observation of ion motion during an excitation event, is used to generate real-time Fourier transform ion cyclotron resonance (FTICR) excitation profiles that track the radial extent of ion motion in a trapped-ion cell. The conventional FTICR excitation profile is collected in a series of individual experiments in which peak magnitude is monitored as excitation voltage is increased. In contrast, SED permits the single-scan detection of ion cyclotron motion within the trapped-ion cell and consequently yields the data that produces a real-time excitation profile. Data analysis techniques are presented that facilitate conversion of a time domain SED profile into an excitation profile. An order of magnitude decrease in the amount of time is required to acquire an excitation profile, while the precision of the measurement is improved. To demonstrate the utility of the technique, it is applied to the study of axial and radial ion loss mechanisms for argon, benzene, and acetophenone ions under different conditions. SED excitation profiles are also used to illustrate the facility of quadrupolar excitation for minimizing radial ion loss.

Journal Article↗

Subdivision of Salmonella enteritidis phage types by plasmid profile typing.

Differentiation of Salmonella enteritidis by plasmid profile typing has been compared to differentiation by phage typing. Examination of the type strains of the 27 S. enteritidis phage types showed that only 11 profile patterns could be identified. Moreover, two profile patterns were found in 15 of the type strains, including those of the two most common phage types in Britain, types 4 and 8. On this basis, plasmid profile typing is not as sensitive as phage typing for the primary subdivision of S. enteritidis. When differentiation of 534 strains of the 27 phage types was attempted using plasmid profiles, variation in pattern suitable for epidemiological subdivision was found in 13 phage types and there were 9 profile patterns in strains of phage type 4. Plasmid profile typing can, therefore, be regarded as an effective adjunct to phage typing for the subdivision of S. enteritidis.

Bacteriophage Typing↗

Use of artificial neural networks to predict drug dissolution profiles and evaluation of network performance using similarity factor.

PURPOSE: To use artificial neural networks for predicting dissolution profiles of matrix-controlled release theophylline pellet preparation, and to evaluate the network performance by comparing the predicted dissolution profiles with those obtained from physical experiments using similarity factor. METHODS: The Multi-Layered Perceptron (MLP) neural network was used to predict the dissolution profiles of theophylline pellets containing different ratios of microcrystalline cellulose (MCC) and glyceryl monostearate (GMS). The concepts of leave-one-out as well as a time-point by time-point estimation basis were used to predict the rate of drug release for each matrix ratio. All the data were used for training, except for one set which was selected to compare with the predicted output. The closeness between the predicted and the reference dissolution profiles was investigated using similarity factor (f2). RESULTS: The f2 values were all above 60, indicating that the predicted dissolution profiles were closely similar to the dissolution profiles obtained from physical experiments. CONCLUSION: The MLP network could be used as a model for predicting the dissolution profiles of matrix-controlled release theophylline pellet preparation in product development.

Cellulose↗

Biorelevant dissolution testing to predict the plasma profile of lipophilic drugs after oral administration.

PURPOSE: To quantitatively compare in vitro dissolution data in biorelevant and compendial media, to investigate whether in vitro differences are reflected in the simulated plasma profile and to specify under which circumstances prediction of the plasma profile of orally administered lipophilic drugs can be achieved. METHODS: Previously published dissolution data from seven products of four lipophilic drugs were compared using the first order model, the RRSBW distribution, and a model based on the Noyes-Whitney theory. Simulated plasma profiles were then obtained using a model-dependent approach. Simulated and observed plasma profiles were compared with the difference factor, f1. RESULTS: No model consistently provided the best fit to the in vitro data, which varied significantly with medium composition. Prediction of the plasma profile was possible (9.6 < or = f1 < or = 34.2) in seven out of eleven cases. CONCLUSIONS: Although prediction of the plasma profile of lipophilic drugs solely on the basis of in vitro data remains an ambitious target, this study shows that the plasma profile of a lipophilic drug can be predicted with appropriate in vitro dissolution data, provided that the absolute bioavailability of the drug is known and the drug has dissolution limited absorption.

Adamantane↗

Gastric pH influences the appearance of double peaks in the plasma concentration-time profiles of cimetidine after oral administration in dogs.

The plasma concentration-time profiles of cimetidine often exhibit two peaks following oral administration of a single dose in the fasted state, while the concurrent administration of some antacids results in a lower extent as well as rate of absorption. In the present work, absorption of cimetidine after a single dose in the fasted state was studied as a function of gastric pH in male beagle dogs to determine whether gastric pH plays a role in the double peak phenomenon and/or can account for the decrease in bioavailability when antacids are coadministered. The extent of absorption of cimetidine was not influenced significantly by gastric pH, indicating that elevation of gastric pH is not the cause of decreases in the bioavailability of cimetidine when it is administered with antacids. Distinct double peaks or plateaux were noted in 8 of 10 plasma profiles when the gastric pH was 3 or below. Irregular absorption behavior was observed in 2 of 6 profiles in the pH range of 3 to 5, while single peaks were observed in all 10 profiles when the gastric pH was maintained at pH > or = 5. It was concluded that gastric pH is a major factor in the generation of cimetidine double peaks. Changes in gastric pH also resulted in changes in the apparent kinetics of absorption. Below pH 5, absorption mostly followed zero-order kinetics (9 of 16 profiles) or a more complex kinetic process involving at least two components to the absorption phase (5 of 16 profiles). At gastric pH > or = 5, however, absorption followed first order kinetics in 7 of 10 profiles. These differences in kinetics of absorption are postulated to arise from variations in gastric emptying as a function of pH and/or carryover effects of gastric pH into the upper intestine.

Absorption↗

Pain-related correlates of MMPI profile subgroups among back pain patients.

The MMPI profiles of 96 male and 218 female patients attending a back pain clinic in a private university-affiliated, orthopedic hospital were analyzed by a hierarchical clustering procedure. The clustering procedure produced four male and four female profile subgroups. The subgroups were compared with one another on the basis of patients' responses to the Cornell Medical Index and revised McGill Pain Assessment Questionnaire. Within the male and female patient cohorts it was found that profile subgroups featuring elevated clinical scales showed greater disruptions of daily activities than did subgroups with relatively unelevated profiles. However, profile subgroups with elevations primarily on the neurotic triad scales reported greater affective disturbance and disruption of daily activities than did subgroups with elevations on both the neurotic triad and relatively psychotic scales. In addition, profile subgroups with subclinical elevations on the neurotic triad scales appeared to have adjusted to their pain experience more poorly than did subgroups that featured scores on nearly all clinical scales that were within one standard deviation of the mean. Suggestions are provided for the use of the MMPI in assessing chronic pain patients and future research regarding cluster analyses of patients' MMPI profiles.

Adolescent↗

Changes in lipid, lipoprotein and apolipoprotein profiles in persons with spinal cord injuries during the first 2 years post-injury.

OBJECTIVE: To investigate changes in lipid, lipoprotein and apolipoprotein profiles in persons with spinal cord injury (SCI) during the first 2 years post-injury, and to determine whether changes in risk profiles were associated with sport activity and/or changes in physical capacity parameters. DESIGN: Risk profiles and physical capacity were investigated in 19 subjects with recent SCI during rehabilitation (t1) and +/- 1 year after discharge from rehabilitation (t2). MAIN OUTCOME MEASURES: Changes in total plasma cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein-A1 (ApoA1), apolipoprotein-B (ApoB) concentrations, the ratios TC/HDL-C, LDL-C/HDL-C, ApoA1/ApoB and HDL-C/ApoA1, and physical capacity (maximal isometric strength, sprint power output, maximal power output, aerobic power). RESULTS: Risk profile parameters changed towards more favorable values at t2, except for HDL-C (P=0.06), TG and HDL-C/ApoA1. Sport activity and changes of the physical capacity were the most important determinants of changes in lipid and (apo)lipoprotein profiles, showing more favorable values with larger increases of the physical capacity and in persons who were physically active. CONCLUSION: Results show that the lipid and (apo)lipoprotein profiles improve in persons with SCI during the first 2 years post-injury, and that improving the physical capacity or being physically active can improve the lipid and (apo)lipoprotein profiles.

Adult↗

Facial profile preferences among various layers of Turkish population.

There are many criteria and methods used to constitute and determine a standardized esthetic concept in orthodontics. However, the subjectivity of the esthetic concept is the common opinion of the authors. Ethnic and racial differences play a major role in diversifying esthetic preferences. The aims of this study were to determine the general esthetic preference of a Turkish population and to find out whether this preference was affected by sex, age, education, social status, geographic location, or personal profile. Toward these aims, eight profile estimates for each sex were morphed by a video imaging technique and then scored by 400 participants. Analysis of variance (ANOVA) and independent sample t-tests were used to compare the preferences of the groups. The orthognathic profile in both sexes was selected as the most preferred profile whereas the convex profile with a prognathic maxilla and a retrognathic mandible were the least preferred. The public also admired fuller and protrusive lips in females and retrusive lips with a prominent nose and chin in males. Sex, age, education, social status, geographic location, and personal profile were also shown to affect the public's profile preferences.

Adolescent↗

Comparative analysis of the impact of risk profile and of drug therapy on survival in CML using Sokal's index and a new score. German chronic myeloid leukaemia (CML)-Study Group.

Survival times in chronic myeloid leukaemia (CML) may vary widely depending on the risk profiles of patients. This fact is frequently not, or not sufficiently, considered in evaluating survival in CML, and some studies do not report risk profiles. Therefore we analysed the relative impact of risk profile and therapy on survival using the median survival times of therapy groups and of risk groups of the three-arm randomized German CML Study I (interferon alpha v hydroxyurea v busulphan; median survival times 65 v 56 v 45 months, n = 490, median observation time 70.4 months). The impact of risk profile (Sokal) on survival as determined by the survival difference between high and low risk patients (40 months) was twice the maximum survival difference between treatment groups (20 months). A similar ratio was obtained after stratification for therapy and for risk profile. Since Sokal's index has been reported to prognostically discriminate IFN-treated patients less well than chemotherapy-treated patients, a new score with better discrimination of IFN-treated patients was also used. The results were similar for both scores. We conclude that the risk profile at diagnosis is still more important for survival of CML patients than therapy. Therefore patients should be stratified according to risk profile for comparisons of survival times between studies and treatment arms.

Adolescent↗

Cytokeratin profiles of the thymus and thymomas: histogenetic correlations and proposal for a histological classification of thymomas.

AIMS: Since cytokeratins (CKs) are useful as differentiation markers for histogenetic and classification studies, we investigated the CK profiles of the thymus and thymomas in an attempt to understand the histogenetic correlation and to propose a histological classification. METHODS AND RESULTS: Nine thymuses and 34 thymomas were immunostained for various CKs of different molecular weights and involucrin. Based on cytomorphology and histoarchitecture, thymomas were classified into spindle cell (SC), small polygonal cell (SPC), mixed, organoid, large polygonal cell (LPC) and squamoid (SQ) thymomas for compiling CK profiles. The thymus was shown to comprise four epithelial compartments, each expressing a different CK profile. Different histological types of thymoma expressed different CK profiles. By correlating the CK profiles of the thymus and thymoma, SPC, SC and LPC thymomas appeared to be related to subcapsular, medullary and cortical cells, respectively. Organoid thymoma recapitulated the structure and CK profile of the normal thymus, while SQ thymoma acquired additional squamous type CK. The applicability and usefulness of the proposed histological classification were evaluated on 147 thymomas by correlating the results with their invasive behaviour. One hundred and thirty-nine cases (95%) could be classified and different histological types correlated strongly with their invasive behaviour. CONCLUSIONS: The thymus is a complex epithelial organ composed of heterogeneous cell types giving rise to various related histological types of thymoma. The results of the CK profile study supports the proposed histological classification, which is pathologically applicable and clinically useful in correlating with invasiveness. This cytomorphological classification, supported by the CK expression patterns, is comparable to Müller-Hermelink classification and the new WHO histological classification except that a separate group of SPC thymoma expressing only CK14 and CK19 was identified and separated from mixed thymoma.

Biomarkers, Tumor↗

Bacterial diversity in maize rhizospheres: conclusions on the use of genetic profiles based on PCR-amplified partial small subunit rRNA genes in ecological studies.

A cultivation-independent approach based on polymerase chain reaction (PCR)-amplified partial small subunit rRNA genes and genetic profiling by single-strand conformation polymorphism (SSCP) was used to characterize the bacterial diversity inhabiting the rhizosphere of maize plants grown on an agricultural field. The community structures of two cultivars, a genetically engineered and a nonengineered variety, different herbicide regimes and soil tillage were compared with each other at two sampling dates. SSCP-profiles were generated with DNA from bacterial cell consortia with primers hybridizing to evolutionarily highly conserved rRNA gene regions. On silver-stained gels, each profile consisted of approx. 50 distinguishable bands. Similarity analyses of patterns recorded by digital image analyses could not detect any difference between cultivars or treatments that was greater than the variability between replicates. A total of 54 sequences recovered from different bands were identified and grouped into operational taxonomical units (OTUs). Surprisingly, only five of 40 OTUs contained sequences of both samplings. Three different bands from a profile were selected to test whether this small overlap was due to an incomplete recovery of sequences. From a faint band, two different OTUs were found when 12 clones were analysed, and from two strong bands 24 and 22 OTUs were detected from a total of 26 and 36 clones, respectively. The OTUs belonged to phylogenetically different groups of bacteria. Gene probes that were developed to target different bands of the profiles, however, indicated in Southern blot analyses that patterns between treatments, replicates and samplings, and even from two different growing seasons were highly conserved. Our study demonstrates that community profiles can consist of more sequences than detectable by staining and that gene probes in Southern blot can be a useful control to investigate the composition of microbial communities by genetic profiles.

Bacteria↗

A critical review of sodium profiling for hemodialysis.

In sodium profiling, the sodium concentration in the dialysis fluid, instead of being constant, follows a time-dependent profile over the course of a hemodialysis session. The main aim of this manipulation is to avoid osmotic disequilibrium by keeping plasma osmolality in the physiological range. Further advantages of sodium profiling are a reduction in the incidence of muscle cramps, improved sodium removal, and improved vascular stability. Many different profiles have been used by various investigators. However, if sodium profiling is not appropriately conducted, sodium accumulation with resulting augmented thirst, increase of interdialytic weight gain, and hypertension may result. Sodium accumulation may, in fact, explain the reduced intradialytic morbidity reported in some short-term sodium profiling studies. Randomized, double-blind studies meeting strict statistical criteria and providing a careful control to maintain equivalent sodium balances between the compared treatments are difficult to perform and have not yet been published. However, because sodium profiling has potential benefits, provided that sodium balance is carefully controlled, it should nevertheless be regarded as a tool that experienced nephrologists can use for the treatment of patients who experience intolerable side effects during standard dialysis.

Blood Volume↗

Offspring of centenarians have a favorable lipid profile.

OBJECTIVES: It is well recognized that a favorable lipid profile provides protection from atherosclerotic cardiovascular disease. Because the major cause of nontraumatic death in the western world is considered to be due to cardiovascular disease, centenarians (defined here as subjects over 95 years of age) are believed to possess "atherosclerotic protective" factors. However, it is impossible to study comparatively the lipid profile in centenarians because of lack of controls. Assuming that certain genes responsible for encoding the lipid phenotype may be inherited, we studied the lipid profile characteristics of offspring of centenarians and compared them with control groups. DESIGN: Prospective cohort study. SETTING: The study was part of the Longevity Genes Project at Albert Einstein College of Medicine. PARTICIPANTS: Ashkenazi Jewish centenarians (n = 27, 98.4 +/- 10.4 years) and their offspring (n = 33, 67.4 +/- 1.4 years). The Ashkenazi Jewish offsprings' spouses, who were not related by blood to the centenarians or their offspring, were used as a control group (n = 26, 68.4 +/- 1.2 years). MEASUREMENTS: The lipoprotein profile of the offspring was compared with the above control group and to a larger control group (age and gender matched) from the National Health and Nutrition Examination Survey (NHANES) III study (without the sample weights, n = 394, 60 to 69 years). RESULTS: Female offspring of centenarians had significantly higher plasma levels of high density lipoprotein-cholesterol (HDL-C) levels compared with controls (70.2 +/- 3.1 vs 59.0 +/- 4.1 mg/dl, P = .029). Male offspring of centenarians had higher plasma levels of HDL-C levels (56.2 +/- 7.1 vs 44.3 +/- 3.4 mg/dl, P = 0.130) and significantly lower LDL-cholesterol (LDL-C) levels (95.0 +/- 6.0 vs 127.0 +/- 8.0 mg/dl, P = .009) compared with controls. CONCLUSION: Offspring of centenarians have a favorable lipid profile compared with controls. These data support the notion that a certain phenotypic lipid profile may be transmitted in families and suggest that a favorable lipid profile may play a role in longevity.

Aged↗

Acylcarnitine profiles in fibroblasts from patients with respiratory chain defects can resemble those from patients with mitochondrial fatty acid beta-oxidation disorders.

Mitochondrial fatty acid beta-oxidation (FAO) is coupled to the respiratory chain (RC). Functional defects of one pathway may lead to secondary alteration in flux through the other. We investigated the acylcarnitine profiles in cultured fibroblasts obtained from 14 healthy subjects, 31 patients with 8 different primary enzyme deficiencies of FAO, and 16 patients with primary RC defects including both isolated and multiple enzyme complex defects. Intact cells were incubated in media containing deuterium-labeled hexadecanoic acid and L-carnitine, and the acylcarnitines analysed using an electrospray tandem mass spectrometer. All FAO-deficient cell lines revealed disease-specific acylcarnitine profiles related to the sites of defects. Some cell lines from patients with RC defects showed profiles similar to those of controls, whereas others had abnormal profiles mimicking those found in FAO disorders. The acylcarnitine profiles of patients with RC enzyme defects were not predictable, and in some patients defects caused by mutations in either nuclear-encoded or mitochondrial DNA were associated with acylcarnitine abnormalities. While in vitro acylcarnitine profiling is useful for the diagnosis of FAO deficiencies, abnormal profiles do not exclusively indicate these disorders, and primary defects of the RC remain a possibility. Awareness of this diagnostic pitfall will aid in the selection of subsequent confirmatory tests and therapeutic options.

Carnitine↗

Changes in the Caucasian male facial profile as depicted in fashion magazines during the twentieth century.

The purposes of this study were to (1) measure changes in the young adult Caucasian male profile through time and (2) describe the male profile depicted in current fashion magazines. Profile photographs (n = 116) of male models collected from leading fashion magazines of the last 65 years were analyzed. They were reproduced as slides, and the images were scanned and projected onto a computer monitor. Soft tissue landmarks were digitized and the profiles were corrected for size differences. Six linear, nine angular, and three proportional parameters were measured. Anteroposterior lip position, lip curl, and vermilion area showed statistically significant correlations (r > or = 31, p < 0.01) with the progression of time. Other angular measurements and vertical facial proportions did not change significantly (r < or = 17, p > 0.05). The results showed that (1) the male profile depicted in fashion magazines has changed significantly with time and the changes were in the area of the lips; and (2) there was a trend of increasing lip protrusion, lip curl, and vermilion display. We conclude that similar to the female profile, the esthetic male profile has changed with time.

Adult↗

Hemodynamic profiles of advanced heart failure: association with clinical characteristics and long-term outcomes.

BACKGROUND: Classifying patients with advanced congestive heart failure (CHF) by baseline measures of congestion and perfusion has been used to estimate hemodynamic status and to select and titrate therapy. We describe clinical characteristics of 4 hemodynamic profiles-wet/cold, wet/warm, dry/cold, and dry/warm-in patients with advanced CHF and assess relations between symptoms, physical signs, and outcomes with each profile. METHODS AND RESULTS: We retrospectively assessed baseline symptoms, physical-examination variables, and 1-year outcomes of 440 patients in a randomized trial. With univariable and multivariable logistic regression, we examined relations of physical-examination variables to hemodynamic profiles. We also assessed the rates of death and death or readmission by profile. Severity of CHF symptoms did not predict the wet-versus-dry profile or cold-versus-warm status, despite significant differences in hemodynamics among groups. Of the physical-examination variables, only a lower proportional pulse pressure was a significant multivariable predictor of the wet category. Among wet patients (n = 348), this same variable was the only significant multivariable predictor of the cold category. For dry patients (n = 92), the cold category was predicted in multivariable analysis by supine heart rate and hepatomegaly. Survival was similar among profiles: wet/cold, 54.2% (n = 91); wet/warm, 58.3% (n = 105); dry/cold, 78.9% (n = 15); and dry/warm, 67.1%, P =.13 (n = 49). Event-free survival also was similar among profiles: wet/cold, 22.0% (n = 37); wet/warm, 29.4% (n = 53); dry/cold, 42.1% (n = 8); and dry/warm, 31.5%, P =.44 (n = 23). CONCLUSIONS: The patient's history and physical examination alone may lead to inaccurate estimation of hemodynamic status and thus suboptimal management for patients with advanced CHF.

Aged↗

[Usability of self-tonometry under ambulatory conditions to obtain daily profiles of intraocular pressure at home].

BACKGROUND: Diurnal profiles of intraocular pressure at opening times in the doctor's office do not deliver enough information, especially nightly and early morning measurements are lacking. Self-tonometry using the automatic self-tonometer "Ocuton S" might be suitable to achieve valid 24-hour IOP profiles without the need to stay in a hospital. MATERIALS AND METHODS: 96 people were taught to use the automatic self-tonometer once. Those who had learnt self-tonometry after this training underwent a diurnal IOP profile for 24 hours in the hospital using Goldmann tonometry and self-tonometry every 4 hours at the same times of day. One to three days later, they created a third IOP profile at home using self-tonometry at the same intervals as at the hospital. The IOP profiles were then tested for equality. RESULTS: 50 people out of 96 were able to perform self-tonometry after one training session. The IOP measurements of all three IOP profiles did not differ by more than 2 mmHg and thus may be considered comparable. There was no significant difference between daily curves, either. CONCLUSIONS: Self-tonometry using the automatic self-tonometer "Ocuton S" appears to be suitable to record diurnal profiles of intraocular pressure at home.

Adult↗

Profile analysis: detection of distantly related proteins.

Profile analysis is a method for detecting distantly related proteins by sequence comparison. The basis for comparison is not only the customary Dayhoff mutational-distance matrix but also the results of structural studies and information implicit in the alignments of the sequences of families of similar proteins. This information is expressed in a position-specific scoring table (profile), which is created from a group of sequences previously aligned by structural or sequence similarity. The similarity of any other sequence (target) to the group of aligned sequences (probe) can be tested by comparing the target to the profile using dynamic programming algorithms. The profile method differs in two major respects from methods of sequence comparison in common use: (i) Any number of known sequences can be used to construct the profile, allowing more information to be used in the testing of the target than is possible with pairwise alignment methods. (ii) The profile includes the penalties for insertion or deletion at each position, which allow one to include the probe secondary structure in the testing scheme. Tests with globin and immunoglobulin sequences show that profile analysis can distinguish all members of these families from all other sequences in a database containing 3800 protein sequences.

Amino Acid Sequence↗