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Biomedical subjects

S W Dennis

Publications and source records attributed to S W Dennis.

3 recordsLinked to original sources

Prediction of postoperative gait velocity in cerebral palsy.

Preoperative and postoperative gait analyses were reviewed for 47 patients with cerebral palsy in an attempt to ascertain predictors of surgical outcome as measured by gait velocity. Higher postoperative velocity correlated with higher preoperative velocity and younger age. Observed velocities in older children were smaller than predicted values. Older children showed either an average decline in velocity from normal for age or no change. Younger children showed an average increase in velocity toward normal for their age. Diagnosis, type of surgery, number of procedures performed and level of ambulation preoperatively were not predictive of postoperative velocity. These results suggests that gait velocity cannot be reliably increased in all children with cerebral palsy undergoing surgery, especially those older than age 12.

Adolescent↗

Role of P-glycoprotein on the CNS disposition of amprenavir (141W94), an HIV protease inhibitor.

PURPOSE: To determine the role of P-glycoprotein (Pgp) on the CNS penetration of the HIV protease inhibitor (PI) amprenavir (141W94) and to test the hypothesis that co-administration of a second HIV PI (ritonavir) could enhance amprenavir's brain penetration in vivo. METHODS: Pgp-mediated efflux was investigated in vitro with Caco-2 cells and in vivo by whole-body autoradiography (WBA). "Genetic" mdr1a/1b double knockout mice, "chemical" Pgp knockout mice generated by administration of the Pgp inhibitor GF120918, and mice pretreated with ritonavir were used in WBA studies to investigate the effects of Pgp modulation on the CNS penetration of amprenavir. RESULTS: Amprenavir, indinavir, ritonavir, and saquinavir had 2- to 23-fold higher transport rates from the basolateral to apical direction than from the apical to basolateral direction across Caco-2 monolayers. Incubation with GF120918 negated this difference, suggesting that the efflux was Pgp-mediated. WBA studies demonstrated a 13- and 27-fold increase in the brain and a 3.3-fold increase in the CSF concentrations of amprenavir in mice pretreated with GF120918 and in mdr1a/1b double knockout mice. In contrast, pretreatment with ritonavir did not alter the CNS exposure of amprenavir. CONCLUSIONS: These results provide evidence that amprenavir and other HIV PIs are Pgp substrates and that co-administration of a specific Pgp inhibitor will enhance amprenavir's CNS penetration in vivo. These results will have an important therapeutic impact in the treatment of AIDS dementia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Variability in gait analysis interpretation.

The purpose of this study was to assess the reliability of interpretation of gait analysis data between physicians and institutions. Gait analysis data from seven patients were reviewed by 12 experienced gait laboratory physicians from six institutions. Reviewers identified problems and made treatment recommendations based on the data provided. Agreement among physicians for the most commonly diagnosed problems was slight to moderate (kappa range, 0.14-0.46). Physicians agreed on identification of soft tissue more than bony problems (intraclass correlation, 0.56 vs. 0.37). Variability regarding surgical recommendations for soft-tissue procedures (kappa range, 0.20-0.64) was similar to that for diagnosis of both soft-tissue and bone problems, although recommendation for hamstring lengthening showed substantial agreement (kappa = 0.64). There was less agreement in recommendation of osteotomies (kappa range, 0.13-0.22). Physicians agreed more on the number of soft-tissue procedures than bone procedures recommended (intraclass correlation, 0.65 vs. 0.19). There was an interinstitutional difference in the frequency of soft-tissue (p = 0.0152) and osseous problem identification (p = 0.0002), as well as in the frequency of recommendations for soft-tissue surgery (p = 0.0004) and osteotomies (p < 0.0001). Although gait analysis data are themselves objective, this study demonstrates some subjectivity in their interpretation. The interobserver variability reported here is similar to that reported for established classification systems of various orthopedic conditions.

Adolescent↗