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Biomedical subjects

Stephen J Lee

Publications and source records attributed to Stephen J Lee.

15 recordsLinked to original sources
PubMed2006

The discovery of an enantioselective receptor for (-)-adenosine from a racemic dynamic combinatorial library.

The use of laser polarimetry detection coupled with HPLC is demonstrated to enable the discovery of enantioselective receptors from racemic dynamic combinatorial libraries. Templating with an enantiopure analyte, such as (-)-adenosine, leads to amplification of one enantiomer of the cyclic dimer. A result confirmed with a pseudo-racemic library wherein one of the enantiomers was d-labeled for mass spec analysis. The resulting dimer is thus an enantioselective receptor for (-)-adenosine.

Adenosine↗
PubMed2006

Tibiofemoral contact mechanics after serial medial meniscectomies in the human cadaveric knee.

BACKGROUND: There is no consensus regarding the extent of meniscectomy leading to deleterious effects on tibiofemoral contact mechanics. HYPOTHESIS: The meniscus aids in optimizing tibiofemoral contact mechanics, increasing contact area, and decreasing contact stress. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve fresh-frozen human cadaveric knees each underwent 15 separate testing conditions-5 serial 20-mm posterior medial meniscectomy conditions (intact, 50% radial width, 75% radial width, segmental, and total meniscectomy) at 3 flexion angles (0 degrees , 30 degrees , and 60 degrees )-under an 1800-N axial load. Tekscan sensors were used to measure total force and medial force, contact area, mean contact stress, and peak contact stress. RESULTS: All posterior medial meniscectomy conditions resulted in significantly decreased contact areas and increased mean and peak contact stresses compared with the intact state (P < .05). The changes in contact mechanics after segmental and total posterior medial meniscectomies were not statistically different (P > .05). Incremental changes in contact area and mean contact stress increased as more peripheral portions of the medial meniscus were removed, whereas peak contact stresses exhibited similar incremental changes throughout all meniscectomy conditions. CONCLUSIONS: The meniscus is a crucial load-bearing structure, optimizing contact area and minimizing contact stress. Loss of hoop tension (ie, segmental meniscectomy) is equivalent to total meniscectomy in load-bearing terms. The peripheral portion of the medial meniscus provides a greater contribution to increasing contact areas and decreasing mean contact stresses than does the central portion, whereas peak contact stresses increase proportionally to the amount of meniscus removed. CLINICAL RELEVANCE: Because the degree of meniscectomy leading to clinically significant outcomes is unknown, a prudent strategy is to preserve the greatest amount of meniscus possible.

Adult↗
PubMed2006

Neuropsychological health in F-111 aircraft maintenance workers.

OBJECTIVE: To contrast subjective and objective measures of neuropsychological health in F-111 aircraft Deseal/Reseal maintenance personnel, against two appropriate comparison groups. METHODS: Exposed and comparison participants completed a postal questionnaire which included a validated memory questionnaire and additional questions relating to possible cognitive symptoms. They also underwent a comprehensive neuropsychological assessment and screening for a past or current disturbance of mood. Multiple linear or logistic regression was conducted for each outcome using exposure group and potential confounders as explanatory variables. RESULTS: There was a strong and consistent excess of self-reported cognitive problems among the exposed group relative to the comparison groups including a 2.8-4.3-fold increase in self-reported symptoms of forgetfulness, loss of concentration and difficulty finding the right word. On detailed neuropsychological testing, the exposed group performed significantly worse than comparisons on tests of psychomotor speed, executive functioning, and new learning/memory. These findings could not be accounted for by disturbances of mood or other potential confounders. CONCLUSIONS: There was a strong and consistent increase in self-reported cognitive problems among the exposed, and small but significant exposure-specific differences on objective tests of cognitive functioning. The findings are consistent with the development of adverse neuropsychiatric changes related to occupational exposure to solvents.

Adult↗
PubMed2006

Prospective evaluation of allograft meniscus transplantation: a minimum 2-year follow-up.

BACKGROUND: Clinical and biomechanical studies have demonstrated the increase in contact pressure and progressive deterioration of the tibiofemoral compartments that occur after partial or complete meniscectomy. Meniscus transplantation has been indicated for the symptomatic postmeniscectomy patient to alleviate symptoms and potentially prevent the progression of articular degeneration. PURPOSE: To report the early-term results after allograft meniscus transplantations from a single institution performed by a single surgeon. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Forty-four meniscus transplants in 39 patients were evaluated at minimum 2-year follow-up using the Lysholm, Tegner, International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, Noyes symptom rating and sports activity, and SF-12 scoring systems; visual analog pain scales; patient satisfaction; and physical examination. Four transplants failed early, leaving 40 transplants in 36 patients for review. Patients were grouped into medial and lateral transplant groups as well as those with isolated and combined procedures. Twenty-one menisci were transplanted in isolation (52.5%), and 19 were combined with other procedures (47.5%) to address concomitant articular cartilage injury. RESULTS: Patients demonstrated statistically significant improvements in standardized outcomes surveys and visual analog pain and satisfaction scales. In 7 patients, treatment had failed at final follow-up. Overall, 77.5% of patients reported they were completely or mostly satisfied with the procedure, and 90% of patients were classified as normal or nearly normal using the International Knee Documentation Committee knee examination score at final follow-up. There were no significant differences in the medial and lateral subgroups, although the lateral subgroup did demonstrate a trend toward greater improvement. No significant differences were noted in the isolated and combined subgroups. CONCLUSION: Meniscus transplantation alone or in combination with other reconstructive procedures results in reliable improvements in knee pain and function at minimum 2-year follow-up. Longer term studies are necessary to determine if transplantation can prevent the articular degeneration associated with meniscectomy.

Adolescent↗
PubMed2006

Traumatic brain injury among Australian prisoners: rates, recurrence and sequelae.

PRIMARY OBJECTIVE: To establish the prevalence, severity, recurrence and sequelae of past traumatic brain injury (TBI) among individuals recently received into custody. RESEARCH DESIGN: Cross-sectional random sample of men recently received into the New South Wales' (NSW) criminal justice system. PROCEDURES: Participants were screened for a history of TBI including the injury setting, severity, treatment and sequelae of up to five separate TBI episodes. OUTCOMES AND RESULTS: Of 200 study participants, 82% endorsed a history of at least one TBI of any severity and 65% a history of TBI with a loss of consciousness (LOC). Multiple past TBIs were common, as were ongoing sequelae. Treatment for the TBI was more common among those TBIs with a LOC compared with no LOC (66% vs. 39%). CONCLUSIONS: Among individuals entering the criminal justice system, past TBI is common and often associated with ongoing neuropsychiatric and social sequelae. Screening for TBI at the point of reception may be warranted to better understand and treat those with ongoing neuropsychiatric sequelae arising from the TBI.

Adolescent↗
PubMed2005

Supramolecular assemblies of DNA with neutral nucleoside amphiphiles.

A neutral uridine-based amphiphile is described which condenses plasmid DNA. AFM studies show that the three distinct structural components of the amphiphile (i.e, nucleobase, alkyl chains, and poly(ethylene glycol)) are required for the formation of DNA-amphiphile supramolecular assemblies on a mica surface.

DNA↗
PubMed2004

Charge-reversal amphiphiles for gene delivery.

Delivering a missing gene or a functional substitute of a defective gene has the potential to revolutionize current medical care. Of the two gene delivery approaches, viral and synthetic vectors, synthetic cationic vectors possess several practical advantages but suffer from poor transfection efficiency. A new approach to gene delivery using charge-reversal amphiphiles is described. This synthetic vector transforms from a cationic to an anionic amphiphile intracellularly. This amphiphile performs two roles: first, it binds and then releases DNA, and second, as an anionic multicharged amphiphile, it destabilizes lipid bilayers. A charge-reversal amphiphile was synthesized and fully characterized, including the supramolecular complex it forms with DNA. Enhanced gene transfection was observed using these vectors compared to current cationic amphiphiles.

Animals↗
PubMed2004

DNA-PEG-DNA triblock macromolecules for reagentless DNA detection.

The sandwich assay is the most common design for electrochemical DNA sensors. This assay consists of three individual DNA components: an immobilized capture strand, a target strand, and a probe strand containing a redox-active reporter group. We report a simplified DNA assay where two strands of ssDNA, the capture and probe strands, are linked together via a flexible poly(ethylene glycol) (PEG) spacer forming an ABA triblock macromolecule. We have developed an electrochemical assay where the detection signal arises as a consequence of a large structural change induced upon hybridization with target DNA. In this system, the DNA-PEG-DNA macromolecule folds or wraps around the target DNA, bringing the ferrocene probe in close proximity to the electrode, affording an electrochemical response.

DNA↗
PubMed2004

Conformationally gated electrochemical gene detection.

The synthesis and characterization of a 26-base DNA hairpin containing both a redox-active reporter (ferrocene) and terminal thiol functionality for electrochemical gene detection is described. This electrochemical DNA sensor exploits electron-transfer dynamics that alter as a consequence of a large structural rearrangement (hairpin-to-duplex) induced by hybridization of the target DNA sequence. Melting temperature and circular dichroism studies confirm that the 26-mer DNA forms a hairpin structure in the absence of target DNA. The loop region of the DNA hairpin is shown to form a stable duplex in the presence of complementary single-stranded DNA. Atomic force microscopy and ellipsometry experiments of immobilized self-assembled DNA monolayers suggest that hybridization with complementary DNA affords a conformational change that alters the electrochemical response.

Base Sequence↗
PubMed2003

Dendritic molecular capsules for hydrophobic compounds.

Reichardt's dye, a highly solvatochromic dye, was encapsulated within poly (glycerol succinic acid) ([Gn]-PGLSA-OH) dendrimers to investigate the interior environment of these dendritic macromolecules. The absorption maximum for the encapsulated Reichardt's dye in water was indicative of a relatively high dielectric constant present within the dye/dendrimer complex. (1)H NMR of the encapsulated complex showed the presence of aromatic protons from Reichardt's dye along with the aliphatic protons of the dendrimer. Additionally, there were substantial changes in T(1) and T(2) times of the encapsulated dye when compared with the free dye, and (1)H NOESY spectra for the complex showed a significant number of intermolecular NOE cross-peaks. These data reveal the close through-space proximity of the dye to the dendrimer and the restricted motion of the encapsulated dye. To demonstrate the potential use of these macromolecules as drug delivery vehicles, the poorly water-soluble anticancer drug 10-hydroxycamptothecin (10HCPT) was encapsulated within a carboxylated PGLSA dendrimer ([G4]-PGLSA-COONa). Cytotoxicity assays with human breast cancer cells showed a significant reduction of cell viability, demonstrating that 10HCPT retains activity upon encapsulation.

Benzene Derivatives↗
PubMed2003

Cognitive screening using a tape recorder: a pilot study.

OBJECTIVES: To determine whether a tape recorder can be used to administer cognitive tests efficiently and yield valid results. DESIGN: Convenience sample. Administration of cognitive test materials by tape recorder and conventional technique. SETTING: Outpatient clinic. PARTICIPANTS: Subjects from memory disorder clinic, hostel accommodation, and community. MEASUREMENTS: Responses to Hopkins Verbal Learning Test-revised, verbal fluency items from the controlled oral word association test, 10-item naming task, a construction task, and speed writing task. RESULTS: Performances on the tape- and clinician-administered battery of tests were highly correlated. Memory impairment was accurately detected using the tape battery. Data from 30 minutes of testing via tape were obtained at the cost to the clinician of 2 to 3 minutes of scoring time. CONCLUSION: Tape-administration of cognitive test material warrants further study as an efficient means of cognitive screening.

Adult↗
PubMed2002

Synthesis and characterization of pi-stacked phenothiazine-labeled oligodeoxynucleotides.

[reaction: see text] A facile procedure for the incorporation of N-methyl phenothiazine as the terminal nucleoside in oligodeoxynucleotides is reported. The phenothiazine nucleoside analogue is synthesized and then incorporated into DNA using an automated DNA solid-phase synthesizer. Phenothiazine-labeled oligodeoxynucleotides form stable B-form duplexes with higher melting temperatures compared to unlabeled DNA duplexes.

Combinatorial Chemistry Techniques↗