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Biomedical subjects

R Shaw

Publications and source records attributed to R Shaw.

188 records · Page 11Linked to original sources

Pharmacology and biological efficacy of a recombinant, humanized, single-chain antibody C5 complement inhibitor in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response that causes substantial clinical morbidity. Activation of complement during CPB contributes significantly to this inflammatory process. We examined the capability of a novel therapeutic complement inhibitor to prevent pathological complement activation and tissue injury in patients undergoing CPB. METHODS AND RESULTS: A humanized, recombinant, single-chain antibody specific for human C5, h5G1.1-scFv, was intravenously administered in 1 of 4 doses ranging from 0.2 to 2.0 mg/kg before CPB. h5G1.1-scFv was found to be safe and well tolerated. Pharmacokinetic analysis revealed a sustained half-life from 7.0 to 14.5 hours. Pharmacodynamic analysis demonstrated significant dose-dependent inhibition of complement hemolytic activity for up to 14 hours at 2 mg/kg. The generation of proinflammatory complement byproducts (sC5b-9) was effectively inhibited in a dose-dependent fashion. Leukocyte activation, as measured by surface expression of CD11b, was reduced (P<0.05) in patients who received 1 and 2 mg/kg. There was a 40% reduction in myocardial injury (creatine kinase-MB release, P=0.05) in patients who received 2 mg/kg. Sequential Mini-Mental State Examinations (MMSE) demonstrated an 80% reduction in new cognitive deficits (P<0.05) in patients treated with 2 mg/kg. Finally, there was a 1-U reduction in postoperative blood loss (P<0. 05) in patients who received 1 or 2 mg/kg. CONCLUSIONS: A single-chain antibody specific for human C5 is a safe and effective inhibitor of pathological complement activation in patients undergoing CPB. In addition to significantly reducing sC5b-9 formation and leukocyte CD11b expression, C5 inhibition significantly attenuates postoperative myocardial injury, cognitive deficits, and blood loss. These data suggest that C5 inhibition may represent a novel therapeutic strategy for preventing complement-mediated inflammation and tissue injury.

Antibodies, Monoclonal↗

Incidence and treatment of visual dysfunction in traumatic brain injury.

The incidence of visual dysfunction and effectiveness of visual exercises in acute traumatically brain injured inpatients in a rehabilitation programme were studied. Vision evaluation norms were established on 23 hospital staff. The evaluation was then administered to 51 inpatients within days after admission. An additional 21 patients were unable to participate, usually due to decreased cognition or agitation. Thirty of 51 (59%) scored impaired in one or more of the following: pursuits, saccades, ocular posturing, stereopsis, extra-ocular movements, and near/far eso-exotropia. For patients having dysfunction in pursuits or saccades, a 2-week baseline was followed by vision exercises. During the baseline interval patients were evaluated by an optometrist to verify therapists' findings. Six patients who participated in several weeks of treatment were evaluated at 2-week intervals by an independent rater. Progress is graphically illustrated. Conclusions were that the suitability of an inpatient vision programme, from our experience, is questionable. However, an initial evaluation proved valuable for informing staff of patients' visual status and for referral to an optometrist/ophthalmologist for further treatment.

Adolescent↗

Troglitazone add-on therapy to a combination of sulfonylureas plus metformin achieved and sustained effective diabetes control.

OBJECTIVE: To elucidate the effect of triple combination oral agent therapy on type 2 diabetes. METHODS: We performed a prospective longitudinal study on 40 patients with type 2 diabetes who had failed to achieve a glycosylated hemoglobin (HbA1c) of < or = 8.0% despite optimal therapy with a combination of sulfonylureas plus metformin. Troglitazone was added and then titrated, with the intent to achieve at least a 1% reduction in HbA1c within 3 months. Responders were reassessed at 6 and 12 months. Nonresponders were reassessed at 6 months; in the absence of a significant HbA1c response, participation in the study was discontinued. RESULTS: Of the 40 study subjects, 25 were responders, 10 were nonresponders, and 5 were withdrawn from the study before completion of 3 months of therapy because of side effects. The 25 responders had a mean baseline HbA1c of 9.9%, which decreased significantly to 7.8% after 3 months of troglitazone therapy and to 7.4% at 6 months and at 12 months. In addition, the fasting blood glucose (FBG) in the responders decreased significantly from 168 mg/dL at baseline to 118 mg/dL at 6 months, which was sustained at 121 mg/dL at 12 months. In the responder group, a mean HbA1c < or = 8% was achieved in 68% at 6 months and sustained in 65% after 1 year. Furthermore, 40% of responders achieved a mean HbA1c < or = 7.0% at 6 months, and 39% sustained this degree of control at 12 months. The 10 nonresponders showed no significant change in HbA1c or FBG during the 6 months of troglitazone therapy. No difference existed in the mean baseline FBG, HbA1c, or C peptide level between the two groups. Responders, however, had a significantly lower mean body mass index (BMI) (31 kg/m2) than did nonresponders (37 kg/m2). Although responders were older than nonresponders (mean age, 65 years versus 55 years), no significant difference was noted in duration of diabetes (11.6 years versus 8.7 years). Multivariate analysis showed that male gender and BMI were the strongest predictors of a response to troglitazone add-on therapy to the prior combination of sulfonylureas plus metformin. CONCLUSION: This study showed that oral therapy with troglitazone added to sulfonylureas plus metformin achieved and sustained a significant improvement in control of diabetes in 71% of patients who had failed to achieve HbA1c < or = 8% with dual oral agent therapy. The positive response was evident within 3 months, reached maximum by 6 months, and was sustained to 12 months of therapy. Therefore, patients who fail to achieve HbA1c < or = 8% with sulfonylureas plus metformin should have at least 3 months of troglitazone add-on therapy before advancing to traditional insulin treatment.

Administration, Oral↗

Fine needle aspiration cytology of pulmonary infarct.

The cytologic features of a pulmonary infarct diagnosed by fine needle aspiration (FNA) cytology are reported in a 54-year-old white man with a prior history of renal transplant surgery. Although the diagnosis of pulmonary embolus was unsuspected, FNA cytology suggested the correct diagnosis, which was confirmed by subsequent radiologic studies. This is believed to be the first reported case of pulmonary infarct diagnosed by FNA cytology. Cytologic features of the entity are discussed along with potential sources for a false-positive diagnosis of malignancy.

Biopsy, Needle↗

Teaching strategies and knowledge retention.

This project compared nurses' knowledge retention after completion of either a competency-based, written self-learning module or a competency-based, didactic lecture module. Using a pretest/posttest quasiexperimental design, a convenient sample was selected from a group of registered nurses who attended a mandatory yearly review of standards from the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and the Occupational Safety and Health Association (OSHA). The 67 subjects were given pretests, the same content material using the two types of presentations, and posttests. An analysis of covariance was used to determine posttest differences between the groups, controlling for pretest scores. Results indicated no significant differences among posttest scores of the treatment group and the control group; alpha level was 0.05. Knowledge retention essentially was the same, regardless of the antecedent teaching methodology. The advantages of one teaching method versus another may be in the flexibility afforded the staff educator. After desired outcomes are identified, a teaching method can be determined based on the staff educators' requirements, the resources available, and the learners' needs.

Adult↗