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Biomedical subjects

C Lackey

Publications and source records attributed to C Lackey.

8 recordsLinked to original sources

Molecular engineering of proteins and polymers for targeting and intracellular delivery of therapeutics.

There are many protein and DNA based therapeutics under development in the biotechnology and pharmaceutical industries. Key delivery challenges remain before many of these biomolecular therapeutics reach the clinic. Two important barriers are the effective targeting of drugs to specific tissues and cells and the subsequent intracellular delivery to appropriate cellular compartments. In this review, we summarize protein engineering work aimed at improving the stability and refolding efficiency of antibody fragments used in targeting, and at constructing new streptavidin variants which may offer improved performance in pre-targeting delivery strategies. In addition, we review recent work with pH-responsive polymers that mimic the membrane disruptive properties of viruses and toxins. These polymers could serve as alternatives to fusogenic peptides in gene therapy formulations and to enhance the intracellular delivery of protein therapeutics that function in the cytoplasm.

Antibodies↗

Current attitudes regarding use of antimicrobial agents: results from physician's and parents' focus group discussions.

Antibiotics are widely prescribed for children with nonspecific upper respiratory tract infections, contributing to the recent emergence of resistant pneumococci. To understand the reasons for the overprescription of antibiotics, we conducted focus groups with parents and with pediatricians and family physicians to assess their attitudes regarding the use of antibiotics. Physicians asserted that their own antibiotic prescribing could be safely reduced. Parental expectation to receive antibiotics was a major factor influencing their overuse of antibiotics. Parents indicated that they would be satisfied with the medical visit even if antibiotics were not prescribed, provided the physician explained the reasons for the decision. This study highlights differences in physician and parent perceptions about antibiotic overuse and suggests that educational efforts to narrow this communication gap will be important for improving antibiotic use.

Adult↗

Esophageal acid clearance during sleep in patients with Barrett's esophagus.

Sleep-related gastroesophageal reflux and esophageal acid clearance have been shown to be important components in the pathogenesis of reflux esophageal disease. Previous studies have suggested that patients with more severe esophagitis are distinguished by an accumulation of acid mucosal contact time during sleep. These data would suggest that patients with Barrett's esophagus should have particularly severe impairment of acid clearance, most notable during sleep. To address this issue, 16 asymptomatic healthy volunteers and 13 patients with Barrett's esophagus were studied. Acid clearance was assessed by timing the reestablishment of an esophageal pH of 4 following the infusion of 15 ml 0.1 N HCl. Sleep was polygraphically monitored in order to objectively determine sleep and waking. The results indicated that while patients with Barrett's esophagus had a marked increase in the frequency of spontaneous gastroesophageal reflux during sleep, they unexpectedly demonstrated faster acid clearance times during both waking and sleep. A greater percentage of arousal responses to acid infusion during sleep was noted in the Barrett's group. It is concluded from these results that patients with Barrett's esophagus can adequately clear acid from the distal esophagus but experience considerable acid mucosal contact through repeated episodes of spontaneous reflux during sleep.

Adult↗

Stricture location in Barrett's esophagus.

Twenty-eight patients with Barrett's esophagus were studied and strictures were present in 13. Two strictures were malignant. Of the 11 benign strictures, six were located at the squamocolumnar junction, while five were located below the squamocolumnar junction. Contrary to previous reports, benign esophageal strictures often occur below the squamocolumnar junction in patients with Barrett's esophagus.

Adenocarcinoma↗