Modification of the Luedeking and Piret model with a delay time parameter for biotechnological lactic acid production.

OBJECTIVES: To obtain a mathematical model that adequately describes the time lag between biomass generation and lactic acid production of lactic fermentations. METHODS: Seven experimental kinetics from other research works were studied to validate our proposal: four studies of Fungal Submerged Fermentation and three cases of Bacterial Submerged Fermentation, including the data recollected by Luedeking and Piret. RESULTS: We introduce a modification to the Luedeking and Piret model that consist in the introduction of a time delay parameter in the model, this parameter would account for the lag time that exists between the production of biomass and lactic acid. It is possible to determine this time delay in a simple way by approximating the biomass and product formation considering that they behave as a first order plus dead time system. The duration of this phenomenon, which is not described with the classical Luedeking and Piret model, is a function of microorganism physiology (ease of biomass growth), environment (nutrients) and type of inoculum. CONCLUSION: The Luedeking and Piret with delay model applications reveal an increase of the R2 in all cases, evidencing the quality of fit and the simplicity of the method proposed. These model would improve the accuracy of bioprocess scaling up.

Chiari malformations: diagnosis, treatments and failures.

Chiari malformations refer to abnormalities of the hindbrain originally described by the Austrian pathologist Hans Chiari in the early 1890s. These malformations range from herniation of the cerebellar tonsils through the foramen magnum to complete agenesis of the cerebellum. In this review, we review the different classification schemes of Chiari malformations. We discuss the different signs and symptoms that the two most common malformations present with and diagnostic criteria. We next discuss current treatment paradigms, including the new measure of possible in utero surgery to help decrease the incidence of Chiari type II malformations. There is also a small discussion of treatment failures and salvage procedures in these difficult cases. Chiari malformations are a difficult clinical entity to treat. As more is learned about the genetic and environmental factors relating to their characteristics, it will be interesting if we are able to predict which treatments are better suited for different patients. Similarly, with the evolution of in utero techniques especially for Chiari II malformations, it will be interesting to see if the incidence and practice of treating these difficult patients will change.

Bioequivalence of an ezetimibe/simvastatin combination tablet and coadministration of ezetimibe and simvastatin as separate tablets in healthy subjects.

OBJECTIVE: To assess the bioequivalence of an ezetimibe/simvastatin (EZE/SIMVA) combination tablet compared to the coadministration of ezetimibe and simvastatin as separate tablets (EZE + SIMVA). METHODS: In this open-label, randomized, 2-part, 2-period crossover study, 96 healthy subjects were randomly assigned to participate in each part of the study (Part I or II), with each part consisting of 2 single-dose treatment periods separated by a 14-day washout. Part I consisted of Treatments A (EZE 10 mg + SIMVA 10 mg) and B (EZE/SIMVA 10/10 mg/mg) and Part II consisted of Treatments C (EZE 10 mg + SIMVA 80 mg) and D (EZE/SIMVA 10/80 mg/mg). Blood samples were collected up to 96 hours post-dose for determination of ezetimibe, total ezetimibe (ezetimibe + ezetimibe glucuronide), simvastatin and simvastatin acid (the most prevalent active metabolite of simvastatin) concentrations. Ezetimibe and simvastatin acid AUC(0-last) were predefined as primary endpoints and ezetimibe and simvastatin acid Cmax were secondary endpoints. Bioequivalence was achieved if 90% confidence intervals (CI) for the geometric mean ratios (GMR) (single tablet/coadministration) of AUC(0-last) and Cmax fell within prespecified bounds of (0.80, 1.25). RESULTS: The GMRs of the AUC(0-last) and Cmax for ezetimibe and simvastatin acid fell within the bioequivalence limits (0.80, 1.25). EZE/ SIMVA and EZE + SIMVA were generally well tolerated. CONCLUSIONS: The lowest and highest dosage strengths of EZE/SIMVA tablet were bioequivalent to the individual drug components administered together. Given the exact weight multiples of the EZE/SIMVA tablet and linear pharmacokinetics of simvastatin across the marketed dose range, bioequivalence of the intermediate tablet strengths (EZE/SIMVA 10/20 mg/mg and EZE/SIMVA 10/40 mg/mg) was inferred, although these dosages were not tested directly. These results indicate that the safety and efficacy profile of EZE + SIMVA coadministration therapy can be applied to treatment with the EZE/SIMVA tablet across the clinical dose range.

Adenosine-induced transient asystole for management of a basilar artery aneurysm. Case report.

Advances in anesthetic and surgical management, such as induced deep hypothermic circulatory arrest and application of temporary clips, have improved outcome for patients with basilar artery aneurysms. Nonetheless, these techniques are associated with significant risks. The authors report a case in which three transient periods of cardiac asystole were induced during basilar artery aneurysm surgery. Adenosine-induced asystole facilitated the safe clipping of the aneurysm by producing consistent periods of profound hypotension and collapse of the aneurysm without the need for temporary clipping. This technique provided unencumbered identification of perforating arteries, precise definition of the local anatomy, and an ideal environment for the safe placement of the aneurysm clip.

Evaluating lyophilized human serum preparations for suitability as proficiency testing materials for high-density lipoprotein cholesterol measurement.

OBJECTIVE: To evaluate the suitability of various commercial preparations for use by the College of American Pathologists as survey materials in assessing high-density lipoprotein cholesterol measurement performance. DESIGN: Lyophilized human serum preparations from six vendors (vendors A through F) were evaluated to determine which material(s) best mimicked the commutability of fresh human serum. Two freshly collected unfrozen pools prepared from donor specimens were analyzed concurrently with the vendor materials to identify sources of variation and possible matrix bias. Each material was evaluated using 5 common precipitation reagents (phosphotungstate-magnesium, phosphotungstic acid, dextran sulfate [50K and 500K], and heparin-manganese). To evaluate how each reagent separates lipoproteins in each material, the lipoprotein separation patterns were profiled using high-pressure liquid chromatography and compared with separation patterns observed for the fresh human serum pools. MAIN OUTCOME MEASURES: Similarities in performance characteristics of vendor material(s) were compared with fresh human serum. RESULTS: Two of the six materials gave separation profiles for the lipoproteins similar to the typical patterns observed for human serum. Material from vendor B showed the best commutability across all of the precipitation reagents and had the best combination of low overall variability (10% for level 1 and 9.4% for level 2) and minimal concentration differences among reagents. CONCLUSIONS: Vendor B was selected by the College of American Pathologists to provide materials for use in assessing performance of lipid and lipoprotein testing in the 1994 Comprehensive Chemistry Surveys. This study demonstrates the great variability that different vendor preparations introduce into the measurement of high-density lipoprotein cholesterol. It also emphasizes the effort required to evaluate the suitability of processed materials for use in proficiency testing.

A Scheme For Conducting Two-Sample Profile Analysis.

A scheme for conducting two-sample profile analysis with Hotelling's T[SUP2] tests and univariate t tests is described. Formulas are provided and a decision tree is presented to guide users in selecting among the tests. Two example problems are worked to illustrate the analysis. The procedure evaluates virtually the same hypotheses as two-factor analysis of variance designs that have a repeated measures factor. However, the procedure has less restrictive assumptions than do repeated measures designs.

The WISC-R factor score profiles of cultural-familial mentally retarded and nonretarded youth.

Factor scores on the Wechsler Intelligence Scale for Children-Revised (WISC-R) were compared for two groups of cultural-familial mentally retarded youth and one group of nonretarded youth. The younger retarded group had a mean CA of 9.5 years; the older retarded group has a mean WISC-R MA of 9.5 years, and the nonretarded group had a mean WISC-R MA and a mean CA of 9.5 years. No significant difference was detected between the retarded and nonretarded groups in their patterns of intellectual strengths and weakness. This finding was consistent with an expectation of the developmental viewpoint of retardation but contrary to a prediction of the difference theory of retardation. Differences were found between the retarded groups in their intellectual strengths and weakness. The older retarded subjects exhibited a relative strength in perceptual organization abilities, whereas the younger ones demonstrated no pattern of comparative strengths and weaknesses.

WISC-R Verbal Performance IQ discrepancies among quay-classified adolescent male delinquents.

Wechsler Verbal-Performance IQ discrepancies have been associated with the broad classification of delinquency, but not with a specific criterion of acting out or psychopathic adjustment. Accordingly, this study examined the hypothesis that the WISC- R Verbal-Performance IQ discrepancy would be larger or more frequent for persons classified as exhibiting a psychopathic delinquent adjustment than for persons classified as either neurotic or subculturally delinquent. Within-subject differences on intellectual measures were obtained for both the psychopathic and subcultural, but not the neurotic, delinquent adjustment classification. This result indicated consistency of intellectual asymmetry across behaviorally diverse delinquent subgroups. No between-group differences were obtained. The results were interpreted as affirming a reliable intraindividual intellectual asymmetry which provides a foundation to model and test hypotheses relating intellectual processes and delinquent behavior.

Magnitude and direction of WISC-R verbal-performance IQ discrepancies among adjudicated male delinquents.

A field study is reported in which the discrepancy between verbal and nonverbal skills among 150 adjudicated male delinquents was assessed by the Wechsler Intelligence Scale for Children - Revised (WISC-R) and evaluated with respect to three interpretations of the observed differences. Alternative explanations were that the verbal-nonverbal disparity among delinquents (a) represented a group-by-test interaction producing unusually large discrepancies, (b) was a function of intelligence level of the sample, and (c) was no more frequent among delinquents than nondelinquents when socioeconomic status (SES) was controlled. Results indicated that the WISC-R Verbal-Performance IQ discrepancy occurred reliably more often among delinquents than among controls. Individual differences within the two groups could be attributed neither to a group-by-test interaction, SES, or intelligence level. It was concluded that cognitive mediators of delinquent behavior differ mainly in degree form those of non-delinquents, and intellectual asymmetry is a concomitant variable significantly associated with delinquent behavior.