Biomedical subjects
Publications and source records attributed to C March.
Potent and selective bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors were synthesized by a novel convergent route. Selectivity and efficacy versus MMPs and TACE could be controlled by appropriate substitution on the scaffolds and by variation of the P1' group. Select compounds were found to be effective in in vivo models of arthritis.
This paper describes the validation of an analytical method for the determination of amphetamine in beagle dog plasma by gas chromatography coupled to mass spectrometry (GC-MS). d-Amphetamine-d(6) was used as the internal standard. The method consisted of a rapid single-step liquid-liquid extraction and derivatization of amphetamine with 2,2,2-trichloroethyl chloroformate, followed by sensitive GC-MS detection. This is the first report utilizing the combination of trichloroethyl chloroformate as a derivatization reagent and a deuterated amphetamine analog as an IS for the quantification of amphetamine in plasma. The method was validated in terms of specificity, curve fit, precision, accuracy, recovery and stability, and was acceptable according to FDA draft guidelines for validation of bioanalytical methods. The limit of detection was 0.65 ng/mL. The calibration range was 5-150 ng/mL. The validated method was successfully employed for the quantitation of amphetamine in dog plasma samples for pharmacokinetic profiling.
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A single pump column switching technique with multidimensional chromatography, flow gradient and wavelength programmed fluorescence detection was developed for simultaneous quantitation of serotonin, fluoxetine and norfluoxetine in rat brain microdialysate. The column switching was configured such that position I of the switching valve employed column I (50 mm length) and column II (250 mm length) in series. This configuration resulted in optimal resolution of serotonin from interfering neurochemicals from rat brain. After elution of serotonin at 13.2 min the valve was switched to position II in which the flow of the mobile phase was directed through column I only. Flow gradient programming was then used to ramp the flow rate from 0.1 to 0.4 ml min-1 which resulted in optimal elution of fluoxetine and norfluoxetine. Strategic optimization of the single mobile phase enabled use of a single pump and detector making the analytical system simple and cost effective. Wavelength programmed fluorescence enabled sensitive detection of the analytes despite the difference in their fluorescence spectrum. The limit of detection for serotonin, norfluoxetine and fluoxetine were 10, 612 and 523 fmol, respectively. Rat brain microdialysate samples demonstrated selectivity for serotonin, fluoxetine and norfluoxetine. The method demonstrates application to the study of site specific neuropharmacokinetics and neuropharmacodynamics of fluoxetine in vivo.
The stability of indocyanine green (ICG) in human serum after storage at -20 and -70 degrees C for an extended time was studied. Serum samples were fortified with ICG at 6.5, 2.0 and 0.3 microgram ml-1, aliquoted, and frozen at -20 or -70 degrees C. The analytic methodology used an internal standard and separation on a reverse phase liquid chromatographic column with UV detection at 240 nm. Samples were prepared for analysis by protein precipitation with acetonitrile. The assay was stability indicating as shown by the complete loss of the ICG peak upon storage at -20 degrees C for 8 weeks. ICG was not stable, as determine by a t test, for 1 week in human serum when stored at -20 degrees C. Storage at -70 degrees C improved stability but the ICG concentration began to fall steadily after 4 weeks of storage.
A competitive enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibodies was developed to measure nicotine in smoke condensates of cigarettes. The ELISA standard curve displays a detection limit of 70 ng/mL and an effective working range of 0.3-4.0 micrograms of nicotine/mL. Using standard samples, ELISA results compare well with theoretical values (r = 0.997). The suitability of the method for industrial routine application was evaluated by measuring the nicotine concentration in 245 cigarette smoke condensates. When ELISA results were compared with those obtained by gas chromatography, a correlation coefficient r = 0.886 was obtained. The assay allows the specific, precise, and accurate determination of nicotine, without any significant interference from other alkaloids also present in tobacco smoke. Preliminary data suggest that the immunoassay could also be applied to other matrices, e.g., tobacco extracts. ELISA equipment requirements are minimum, simple, and low-cost, and an unskilled person could perform 150 analysis in a working day. On the basis of these features, ELISA is proposed as a promising alternative to instrumental methods for some industrial applications.
Accuracy and precision are the most important criteria in the assessment of an analytical method, and monitoring quality control during sample analysis is essential to ensure the validity of reported results. Various approaches to testing accuracy, precision, and quality control were applied to 10 analytes from seven chromatographic bioanalytical methods. These methods include fixed interval bias and significance testing for accuracy; fixed interval percentage relative standard deviation (%RSD) and analysis of variance (ANOVA) approaches for precision; +/- 20% fixed range, 99% confidence interval, multiple rules, and range chart for individuals approaches for quality control acceptance criteria. Quality control approaches were also applied to the entire run and to a bracketed approach whereby results are considered valid only if bracketed by acceptable quality control. Accuracy and precision were assessed for six runs of each analyte at three concentrations established to represent the calibration range of the analytical method. Quality control acceptance criteria were evaluated using all data sets from each of the analytical methods collected during the course of running various numbers of real samples. The data suggest that the fixed interval bias criteria for accuracy was a more liberal method of accuracy assessment because three of the seven methods would have been rejected according to the significance testing criteria whereas all were acceptable by the fixed internal bias criteria. Precision can be effectively assessed for between- and within-run data by criteria set on unconfounded %RSD values or by separation of the sources of variation using an ANOVA approach applied to confounded data.(ABSTRACT TRUNCATED AT 250 WORDS)
A rapid and simple external-standard high-performance liquid chromatographic (HPLC) method has been developed for the determination of the concentration of furosemide in plasma. The analyte is extracted with a C-2 ethyl sorbent. On-line elution of the analyte into the HPLC system is accomplished with an advanced automated sample processor (Varian). Furosemide is quantified by fluorescence detection within a linear range of 25 to 1000 ng/mL (average correlation coefficient, 0.9998), with a limit of detection of 1.8 ng/mL. Both internal- and external-standard procedures were evaluated, and the external-standard procedure demonstrated superior characteristics. The external-standard procedure was precise to within a relative standard deviation of 8% and accurate with less than 3% error throughout the concentration range studied. The external-standard HPLC method was used to analyze the concentration of furosemide in greater than 1000 plasma samples obtained from patients with either normal kidney function or renal failure who had received furosemide either orally or intravenously in an experimental setting.
Calibration in chromatographic biopharmaceutical analysis is a major determinate of method performance and many methods have been proposed to evaluate an appropriate calibration model, to determine the linear range and to evaluate the goodness of fit. Ten chromatographic bioanalytical methods have been evaluated in this work by observation of concentration-response curves, linearity plots, calculation of concentration residuals, correlation coefficients and lack of fit analysis. These methods were applied to univariant linear regression, weighted regression, polynomial regression and power fit models in order to determine the most appropriate way to establish and evaluate calibration functions. It was found that weighted linear regression provided the most appropriate calibration function for eight of the 10 methods studied, whereas unweighted regression and the power fit model proved appropriate for one each of the other two methods. The choice of calibration function was best accomplished through observation of calculated concentration residuals. Linearity and sensitivity plots were of little value for assessment of linearity through the selected calibration range if conventional (+/- 5%) tolerance limits are employed. Validation of the calibration model can be accomplished by demonstrating the concentration residuals and the slope of the log concentration-log response plots are within reasonable tolerance limits or by lack of fit analysis. Correlation coefficients were demonstrated to be of little value for this purpose and the quadratic approach to linearity validation was in disagreement with other methods in four of the 10 methods evaluated.
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Nursing home administrators and sponsors should look to fund-raising as a way to increase their facilities' revenues. The board should first appoint a development coordinator and a special board to be responsible for the fund-raising program. The nursing home can reach potential contributors by regularly sending printed material to specially selected persons from its mailing list. The staff must know the procedures to follow when someone wants to make a donation (e.g., to whom the check should be made payable). To generate interest and to motivate contributors, the fund-raising board should identify specific needs for which the contributions will be solicited. A computer program can help keep track of to whom acknowledgements must be sent. Options for a fund-raising program include memorial and honor gifts, gifts in kind, grants and special gifts, special events, deferred gifts, educational programs, and membership clubs.
Interleukin-1 beta (IL-1 beta) is released from an inactive precursor by a proteolytic cleavage. A monocytic protease has been identified that appears to be involved in the physiological activation of this cytokine. Two situations have been found in which precursor IL-1 beta exists without the monocytic processing enzyme, and in these cases other proteases, such as neutrophil elastase, cathepsin G and cathepsin L, may be involved in generating the active cytokine.
Antimicrobial activities were tested for 22 plant species collected in the Valencian Community, using 9 different fungal and 6 bacterial strains which contaminate food and crops. Some of them showed fungizidal and bactericidal activity against some of the microorganisms tested.
Torsemide is a new diuretic drug with a profile of action similar to that of furosemide. The high potency of torsemide results in low dose therapy and causes problems for the pharmacokinetic study of the drug due to low plasma levels. Described here are methods for the analysis of torsemide and two metabolites in plasma and urine using solid-phase extraction and liquid chromatography. The limits of quantitation are 10 ng/mL for plasma and 20 ng/mL for urine. The relative standard deviations for precision are less than 10% for most analytes at most concentrations in the calibration range. The recoveries from plasma were 94.3, 92.9, and 95.6%, and from urine were 77.5, 66.6, and 76.5% for torsemide and metabolites M1 and M5, respectively. The method was suitable for pharmacokinetic studies. Data from a normal volunteer are presented.
A patent urachal sinus, as well as other urachal anomalies, may complicate laparoscopy. Perforation of such a sinus occurred during laparoscopy. Laparotomy or repeat laparoscopy may be necessary to excise the urachal anomaly.
The concentration uniformity of an extemporaneously prepared ranitidine suspension was studied. To prepare the ranitidine suspension, 36 150-mg tablets were pulverized and suspended in 180 mL of distilled water. This mixture was diluted with simple syrup to a total volume of 360 mL, resulting in a final ranitidine concentration of 150 mg/10 mL. Samples from each of three bottles that had been filled with 60 mL of the suspension were assayed for ranitidine content by high-performance liquid chromatography. The sedimentation of suspended ranitidine tablet particles was studied by visual observation of the setting process in 10-mL samples from the same batch. The overall mean concentrations (in milligrams per milliliter) of ranitidine were 14.53, 15.25, 13.92, 12.67, and 12.72 at 0, 3, 7, 14, and 21 days, respectively. Compared with baseline, the difference in the ranitidine concentration was not significant over days 0-7. The ranitidine concentration was significantly reduced during the following time intervals: days 0-14, days 0-21, and days 7-21. In the settling experiments, the mean time (+/- S.D.) for sediment to first appear on the test tube bottom was 14.67 +/- 5.35 seconds. Approximately 40-50% (mean level = 3.2 mm) of the total sedimentation level (mean level = 7.3 mm) was observed one minute after shaking. The uniformity of ranitidine suspensions compounded according to procedures described in this report possibly could be improved with sonication. The ranitidine suspension should be well shaken, the dosage should be measured immediately after shaking, and the suspension should be used within seven days of compounding.
Geriatrics, which is still a young medical specialty, is only just beginning to discover how the elderly react to illness and treatment. One of the discoveries is that the elderly do not always respond or show symptoms in the same way as a younger patient. Some basic understanding of the effects of aging on a person can lead to useful strategies in meeting the elderly's needs. A lack of understanding about changes in the elderly's sense organs probably causes the most frustration in the relationship between the elderly patient and the care provider. The ability to see diminishes in approximately 20 percent of the elderly. Approximately one third experience a hearing loss. The elderly have a decreased number of taste buds, especially those affecting sweet and salty tastes. Their ability to perceive pain, pressure, and temperature may decrease as well. The healthcare professional should be aware of the difference in the geriatric data base from that at other life stages and should look for clues that the elderly patient is suffering from diminished senses.
Religious institutes must plan to meet the financial needs of their retired members and must consider the environment, living arrangements, and quality of life after retirement. Recently ServantCor, a Catholic human services system based in Kankakee, IL, helped two institutes of religious women plan a more comprehensive retirement program by developing a model for them to assess their retirement needs. The model was based on information from eight sources: The institute's current practice. Projected demographic data on number of retired sisters and number of infirmary beds that would be needed over the next two decades. Questionnaires on all the sisters' perceptions of retirement. Interviews with selected sisters concerning issues covered in the questionnaires. Site visits to residences for retired sisters. Geriatric services available in the area where the largest number of retired sisters lived. Retirement programs for other religious institutes in the area. The adequacy of the institute's financial resources. At one institute, focus groups with older laypersons also were held to determine ministry possibilities in the area. Six months after the studies' completion, the provincials of the two institutes said that it helped them in planning to meet the sisters' future infirmary needs. They cited an increased awareness of the need for a holistic approach to retirement. The provincial at one institute said that members' attitude toward the infirmary had improved. At the other institute, they obtained a broader perspective on ministry possibilities to the elderly in the area.