Noninvasive cardiac output monitor to quantify hydration status in ischemic stroke patients: A feasibility study.

BACKGROUND: Individuals who are dehydrated, volume contracted or both at the time of hospitalization for acute ischemic stroke have worse clinical outcomes than do individuals with optimal volume status. Currently, there is no gold standard method for measuring hydration status, except indirect markers of a volume contracted state (VCS) including elevated blood urea nitrogen (BUN)/creatinine ratio. We sought to test the feasibility and acceptability of a non-invasive cardiac output monitor (NICOM) for the measurement of hydration status in a group of hospitalized ischemic stroke patients, and explore the relationship with a common indirect laboratory-based measure of VCS. METHODS: We performed a prospective observational feasibility study of hospitalized acute ischemic stroke patients. We collected hemodynamic parameters using the NICOM device before and after fluid auto-bolus via passive leg raise and BUN/creatinine ratio. Successful acquisition of relevant hemodynamic data was the primary objective of this study. We explored agreement between the NICOM results and BUN/creatinine ratio using Cohen's kappa statistic. RESULTS: Thirty patients hospitalized with acute ischemic stroke were enrolled. We found that 29/30 patients tolerated assessment with NICOM. Hemodynamic data were collected in all 30 patients. Data capture took an average of 10 min(SD ± 112 s). Agreement between NICOM and BUN/creatinine ratio was 70%; (expected agreement 51%; kappa 0.38). Agreement was stronger in the cohort without history of diabetes (81% agreement, kappa 0.61). CONCLUSIONS: NICOM assessment was feasible in hospitalized stroke patients. The identification of an objective, real-time measure of hydration status would be clinically useful, and could allow precise, goal-directed care.

Effectiveness of detergent-disinfecting agents on Escherichia coli 54127 biofilm.

Detergent-disinfecting agents (dD) are used daily for cleaning reused medical devices. We have devised a simple method to test dD detergent activity (DA) using an E. coli 54127 biofilm prepared in haemolysis glass tubes, which are cleaned with test dD, according to supplier's recommendations. Crystal violet 0.05% is used to colour the residual biofilm after dD (or tap water control) application. The biofilm quantification was made indirectly by measuring the absorbance of crystal violet at 585 nm. A measure of the detergent effectiveness called DA was calculated as the percentage reduction of colour from a tap water control. Fifteen products including enzymatic and non-enzymatic dDs were evaluated. Most enzymatic dDs gave a high DA, as did some non-enzymatic products. Thus, the view that enzymatic dDs are more effective than non-enzymatic dDs, put forward by some manufacturers, should be regarded with caution. The DA determination should help infection control teams choose, within the wide range of products available on the market, the most effective dD based on both its detergent and disinfecting activity.

From computational modelling of the intrinsic apoptosis pathway to a systems-based analysis of chemotherapy resistance: achievements, perspectives and challenges in systems medicine.

Our understanding of the mitochondrial or intrinsic apoptosis pathway and its role in chemotherapy resistance has increased significantly in recent years by a combination of experimental studies and mathematical modelling. This combined approach enhanced the quantitative and kinetic understanding of apoptosis signal transduction, but also provided new insights that systems-emanating functions (i.e., functions that cannot be attributed to individual network components but that are instead established by multi-component interplay) are crucial determinants of cell fate decisions. Among these features are molecular thresholds, cooperative protein functions, feedback loops and functional redundancies that provide systems robustness, and signalling topologies that allow ultrasensitivity or switch-like responses. The successful development of kinetic systems models that recapitulate biological signal transduction observed in living cells have now led to the first translational studies, which have exploited and validated such models in a clinical context. Bottom-up strategies that use pathway models in combination with higher-level modelling at the tissue, organ and whole body-level therefore carry great potential to eventually deliver a new generation of systems-based diagnostic tools that may contribute to the development of personalised and predictive medicine approaches. Here we review major achievements in the systems biology of intrinsic apoptosis signalling, discuss challenges for further model development, perspectives for higher-level integration of apoptosis models and finally discuss requirements for the development of systems medical solutions in the coming years.

Rapid direct determination of lead in evaporated milk by anodic stripping voltammetry without sample pretreatment.

The method presented describes the direct determination of lead in evaporated milk in which the milk ashing step prior to analysis is eliminated. Digital instrument readout units are microgram Pb/mL milk. Total analysis time after instrument calibration is less than 3 min per sample. Range of the method is 0.05-1.0 ppm lead in milk, and precision of the method expressed by relative standard deviation of duplicate pairs ranged from 30% at 0.1 micrograms/mL to 3% at 1.0 micrograms/mL of lead in milk. The method compares favorably with the AOAC official first action anodic stripping voltammetric method (25.074). In addition, the method appears to work equally well for skim evaporated milk, sweetened condensed milk, and nonfat powdered dry milk when the latter two are reconstituted with water according to product label instructions. Recovery and interference studies are presented.

Leak in evaporated milk by anodic stripping voltammetry and atomic absorption spectrophotometry: cooperative interlaboratory study.

The results of a cooperative study on the determination of lead in evaporated milk, using a double blind referee technique, are reported. This study was designed to determine the normal variability of methods currently used for lead analysis by canned food industry laboratories. Twenty-three laboratories participated in this study. Each laboratory was instructed to use atomic absorption spectrophotometry (AOAC 25.065), anodic stripping voltammetry, or carbon rod atomic absorption spectrophotometry. Overall, the results appear to be in close agreement with the spiking levels. The coefficient of variation for all laboratories was 36.0% at the 0.15 ppm lead level and 16.8% at the 0.40 ppm lead level.

Direct analysis of lead in fruit juice by anodic stripping voltammetry with no prior sample preparation.

A method is presented for determining lead in fruit juice in less than 3 min after instrument calibration. The range examined is 0.01 to 1.3 ppm lead. The method is compared with 3 other methods in general use. Standard error of estimates between the methods compared range from 0.023 to 0.051 ppm for a set of 50 samples and from 0.037 to 0.091 ppm for a set of 9 samples. Regression correlation coefficients between methods range from 0.968 to 0.995. Judged by the comparisons, the direct method is precise and accurate over greater than a 100-fold range of lead concentrations.

Ritodrine: a beta-adrenergic receptor antagonist in human amnion.

OBJECTIVE: Human amnion is important in the initiation of labor. Ritodrine, when administered as a tocolytic, is found unchanged in amniotic fluid. We characterized effects of ritodrine binding to beta-adrenergic receptors in amnion and amniocytes. STUDY DESIGN: Iodine 125-iodopindolol, beta-adrenergic receptor agonists, and beta-adrenergic receptor antagonists were used to describe binding characteristics. Experiments were designed with and without isoproterenol and ritodrine to study intracellular cyclic adenosine 3'5'-monophosphate and prostaglandin E2 release. RESULTS: Scatchard analysis revealed a single class of saturable binding sites, with maximum binding capacity of 70.0 +/- 17.2 fmol/mg protein (n = 12) and with high-affinity dissociation constant of 458.9 +/- 72.1 pmol/L. Agonists and antagonists competed for the 125I-iodopindolol binding site consistent with a beta 2-adrenergic receptor. Hill coefficients were 0.6 to 0.8 for agonist competition and 1.0 for antagonist competition and ritodrine. Stimulation with isoproterenol resulted in dose-dependent increases in cyclic adenosine 3'5'-monophosphate and prostaglandin E2. Ritodrine failed to stimulate cyclic adenosine 3'5'-monophosphate and inhibited isoproterenol-stimulated cyclic adenosine 3'5'-monophosphate and prostaglandin E2 production. CONCLUSION: In human amnion binding of ritodrine to beta 2-adrenergic receptors and lack of ritodrine-mediated postreceptor effects are characteristic of a beta 2-adrenergic antagonist.

Direct determination of lead in evaporated milk and apple juice by anodic stripping voltammetry: collaborative study.

A method for the direct determination of lead in evaporated milk and in fruit juice with no prior sample digestion was successfully collaborated by 13 laboratories. The anodic stripping voltammetric (ASV) method studied consisted of adding 0.2 mL aliquots of evaporated milk or 0.3 mL aliquots of fruit juice to 2.9 mL of a dechelating reagent, Metexchange. The reagent-sample mixture is then analyzed for lead by ASV with no further sample preparation. Each collaborator received 24 samples, 2 each at 5 different levels (0.07-0.70 ppm for spiked evaporated milk and 0.09-0.87 ppm for spiked apple juice) along with duplicate practice samples of labeled lead content at each of 2 levels for each sample type. All unknowns were coded with random numbers. Approximately 69% of the reporting laboratories had never analyzed either evaporated milk or fruit juice for lead. Average time between receipt of samples and reporting of results was 1.6 days for all laboratories. The pooled variations between duplicate determinations for apple juice and evaporated milk were 0.00059 and 0.00043, respectively. The method was adopted official first action for both fruit juice and evaporated milk.

Analysis of total arsenic in urine and blood by high speed anodic stripping voltammetry.

A method for the measurement of parts per billion levels of total arsenic in urine and blood is described. Samples are wet ashed with a mixture of HNO3, HCIO4, and H2SO4 acids. Ashed materials are subjected to a reductillationTM procedure to reduce As (V) to As (III) and to separate arsenic from the sample matrix. Collected arsenic is then quantitated by anodic stripping voltammetry (ASV) at a gold film electrode. ASV analysis time is only 2 minutes. By simultaneous reductillation of 4 samples, ppb arsenic determinations can be accomplished at a rate of about 12 per hour. The method is as accurate, precise and reliable at the nanogram level as the more universally accepted colorimetric techniques are at the microgram and milligram levels. For replicate analysis of real samples, method precision ranged from +/- 1.4 ppb at the 5 ppb level to +/- 0.96 ppb at the 25 ppb level. Accuracy is estimated at +/- 6% over the range 5 to 500 ppb arsenic.

Polyprenyl phosphate biosynthesis in Mycobacterium tuberculosis and Mycobacterium smegmatis.

Mycobacterium smegmatis has been shown to contain two forms of polyprenyl phosphate (Pol-P), while Mycobacterium tuberculosis contains only one. Utilizing subcellular fractions from M. smegmatis and M. tuberculosis, we show that Pol-P synthesis is different in these species. The specific activities of the prenyl diphosphate synthases in M. tuberculosis are 10- to 100-fold lower than those in M. smegmatis. In M. smegmatis decaprenyl diphosphate and heptaprenyl diphosphate were the main products synthesized in vitro, whereas in M. tuberculosis only decaprenyl diphosphate was synthesized. The data from both organisms suggest that geranyl diphosphate is the allylic substrate for two distinct prenyl diphosphate synthases, one located in the cell membrane that synthesizes omega,E,Z-farnesyl diphosphate and the other present in the cytosol that synthesizes omega,E,E,E-geranylgeranyl diphosphate. In M. smegmatis, the omega,E, Z-farnesyl diphosphate is utilized by a membrane-associated prenyl diphosphate synthase activity to generate decaprenyl diphosphate, and the omega,E,E,E-geranylgeranyl diphosphate is utilized by a membrane-associated activity for the synthesis of the heptaprenyl diphosphate. In M. tuberculosis, however, omega,E,E,E-geranylgeranyl diphosphate is not utilized for the synthesis of heptaprenyl diphosphate. Thus, the difference in the compositions of the Pol-P of M. smegmatis and M. tuberculosis can be attributed to distinct enzymatic differences between these two organisms.