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Biomedical subjects

C K Lee

Publications and source records attributed to C K Lee.

At least 19 recordsLinked to original sources

The role of radiation therapy in Hodgkin disease: experience and controversy. The 54th annual Janeway Lecture: 1989.

BACKGROUND: Beginning in 1970, a series of patients with Hodgkin disease were treated at the University of Minnesota, after staging laparotomy, with radiation therapy (RT) for Stage I, II, and IIIA Hodgkin disease. This report is an analysis of the results of the treatment and of treatment modifications. METHODS: From 1970 to 1974, all patients were treated with standard RT. In 1975, an analysis of these patients indicated that patients with large mediastinal mass (LMM) and patients with Stage IIIA spleen-positive (IIIAS+) disease had a higher recurrence rates than patients without these factors. Subsequently, a schema of radical radiation therapy (RRT) was devised, which included low-dose lung RT for patients with LMM and low-dose liver RT for patients with IIIAS+ disease. RESULTS: Analysis of the results of the two treatments indicates that the use of low-dose lung RT in patients with LMM and low-dose liver RT in patients with IIIAS+ Hodgkin disease produced survival and recurrence-free survival results equivalent to those achieved by use of combined modality treatment (CMT) or chemotherapy (CT) alone. CONCLUSIONS: The use of RT with whole lung and liver irradiation for patients with LMM and IIIAS+ Hodgkin disease, respectively, produces results that are equivalent to those of CMT or CT alone with the advantage of a decreased incidence of second malignant neoplasms. In addition, patients who do not respond to initial RT have a greater chance of being saved with chemotherapy than do patients initially treated with CMT of being saved with RT. The authors suggest that radical RT is the treatment of choice for patients with LMM and/or IIIAS+ Hodgkin disease.

Adolescent

DNA adduct formation in mice following dermal application of smoke condensates from cigarettes that burn or heat tobacco.

A prototype cigarette that heats tobacco (test cigarette), developed by R.J. Reynolds Tobacco Company, has yielded consistently negative results in several in vivo and in vitro genetic toxicology tests. The objective of the present study was to evaluate the potential of cigarette smoke condensate (CSC) from the test cigarette to induce DNA adducts in mouse tissues and compare the results with those obtained with CSC from a reference tobacco-burning cigarette (1R4F). CD-1 mice were skin-painted with CSC from reference and test cigarettes three times a week for 4 weeks. The highest mass of CSC applied was 180 mg "tar" per week per animal for both reference and test cigarette. DNA adducts were analyzed in skin and lung tissues using the 32P-postlabeling method with the P1 nuclease modification. Distinct diagonal radioactive zones (DRZ) were observed in the DNA from both skin and lung tissues of animals dosed with reference CSC, whereas no corresponding DRZ were observed from the DNA of animals dosed with either test CSC or acetone (solvent control). The relative adduct labeling (RAL) values of skin and lung DNA from reference CSC-treated animals were significantly greater than those of the test CSC-treated animals. The RAL values of the test CSC-treated animals were no greater than those of solvent controls. The negative results in DNA adduct assays with test CSC are consistent with all previous results of in vivo and in vitro genetic toxicology testing on this cigarette and provide additional evidence that smoke condensate from the test cigarette is not genotoxic.

Animals

A new method for measurement of femoral anteversion. A comparative study with other radiographic methods.

A new biplanar method of measuring femoral anteversion, which may be considered a modified Magilligan's method, is described. In addition to the true antero-posterior radiograph, a true translateral radiograph is taken, instead of a transcervical lateral radiograph as in the Magilligan method. The acute angles (alpha and gamma) between the long axes of the shaft and neck of the femur on both the antero-lateral and lateral radiographs are measured. The angle (gamma') of anteversion is obtained by the trigonometric formula; tan gamma' = tan/tan alpha. The femoral anteversion in 20 adult dried femora and 40 femora in 20 children was measured by the Magilligan method, the authors' method and the conventional CT method. Compared with direct measurement in the dried femora, it was found that both the Magilligan and the authors' methods tended to overestimate and the CT method tended to underestimate (p < 0.05) the anteversion. In children's femora, a similar trend was observed among the three methods and the measurements by each method differed significantly from the other (p < 0.05). We feed that our method of biplanar measurement of femoral anteversion is more accurate, although probably marginally, than the conventional Magilligan method. It also has some relative advantages in clinical application in that positioning is easier, rotation is better controlled, and less time is consumed.

Adolescent

Fourteen-day inhalation study in rats, using aged and diluted sidestream smoke from a reference cigarette. II. DNA adducts and alveolar macrophage cytogenetics.

The chemical constituents of cigarette smoke are greatly diluted in environmental tobacco smoke (ETS). In the typical indoor environment where cigarettes are smoked, the mean value of respirable suspended particles is approximately 0.1 mg/m3. In this study, we used aged and diluted sidestream smoke (ADSS) of 1R4F University of Kentucky research cigarettes as a surrogate for ETS and exposed Sprague-Dawley rats nose-only to 0, 0.1, 1.0, and 10 mg wet total particulate matter (WTPM)/m3 for 6 hr per day for 14 consecutive days. DNA from lung, heart, larynx, and liver was tested for adduct formation after 7 and 14 days of exposure and after 14 days of recovery. In addition, alveolar macrophages from animals exposed for 7 days were examined for chromosomal aberrations. Exposure-related DNA adducts were not observed in any of the animals at 0.1 or 1.0 mg WTPM/m3, which represent ambient and 10-fold exaggerated ETS concentrations, respectively. Slight diagonal radioactive zones, characteristic of adducts observed in human smokers and in animals exposed to mainstream smoke, were observed, but only in lung and heart DNA of animals exposed to the highest concentration of ADSS (10 mg WTPM/m3), a 100-fold exaggeration of typical field measurements of ETS. The mean relative adduct labeling values (+/- SE) were 8.7 (+/- 0.2) adducts per 10(9) nucleotides for lung DNA and 5.7 (+/- 0.7) adducts per 10(9) nucleotides for heart DNA after 14 days of exposure. No elevation in chromosomal aberrations was observed in alveolar macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation

Use of ciprofloxacin in an infant with ventriculitis.

Ciprofloxacin was used successfully in a neonate with ventriculitis caused by a multiply resistant strain of Enterobacter cloacae. Limited pharmacokinetic data indicated that adequate concentrations of drug could be attained in cerebrospinal fluid.

Cerebral Ventricles

The mechanical properties of the canine lumbar disc and motion segment.

A study was initiated to measure the mechanical properties of the canine lumbar spine disc and motion segment at two specific levels. Compressive stiffness was determined to be 717.8 N/mm at L2-3 and 949.0 N/mm at L5-6. Torsional stiffness was found to be 1.04 Nm/deg at L2-3 and 1.72 Nm/deg at L5-6. These data were then compared to human lumbar spine disc and motion segment properties that have been reported in the literature. After normalizing for size differences, the canine lumbar disc showed a similar axial modulus (14.03 MPa for L2-3 and 16.30 MPa for L5-6) and a significantly higher torsional modulus (30.80 MPa for L2-3 and 26.17 MPa for L5-6) when compared to human values. The relative contributions of ligaments, posterior elements, and intervertebral disc to overall stability of the motion segment was found to be similar in canines and humans. As has been shown in human spine research, the posterior elements including the facet joints were found to be significant structures in providing torsional rigidity of the canine spine.

Animals

Shear stability of an elastomeric disk spacer within an intervertebral joint: a parametric study.

A parametric study was conducted to compare the resistance to shear force provided by three surgical implantation techniques and three endplate designs for use with a polymeric lumbar intervertebral disk spacer. While under an axial load, the implant was pushed out laterally through the surgical window created for implantation. Force at 0.3 mm displacement, slope of the initial portion of the force-displacement graph, and maximum force were measured. The results indicate that implants with pegs, inclined planes, or domes on the surfaces of the disk will add significantly to the shear stability of the implant while maintaining the simplicity of a single part device.

Animals

Determinants of substrate recognition by poliovirus 2A proteinase.

Poliovirus proteinase 2A (2Apro) is autocatalytically released from the viral polyprotein by cleavage in cis of a Tyr-Gly dipeptide at its own amino terminus, resulting in separation of the P1 structural and P2-P3 nonstructural protein precursors. A second Ty-Gly dipeptide within 3D polymerase is cleaved by 2Apro in trans, but this is not essential for viral proliferation. The mechanism which limits cleavage to only 2 of the 10 Tyr-Gly dipeptides within the poliovirus polyprotein has not been characterized. We have therefore undertaken a systematic mutational analysis of the VP1-2A site to elucidate determinants of substrate recognition by 2Apro. The P2 and P1' positions are important determinants for cis cleavage of this site, whereas a variety of substituents could be tolerated at the P2', P1, and P3 positions. The requirements for trans cleavage of this site were more stringent. We found that the 2Apro of coxsackievirus type A21 and rhinoviruses 2 and 14 have stringent requirements similar to those of poliovirus 2Apro for cleavage in trans.

Amino Acid Sequence

An unusual combination of trisomy 21 and partial trisomy 5q.

The authors describe a male newborn with multiple congenital anomalies; craniofacial dysmorphism, bilateral cleft palate and lip, ambiguous external genitalia with absence of phallus, ventricular septal defect, agenesis of olfactory bulbs, and presence of small round cells simulating migration defect in the cerebellar white matter. Cytogenetic study demonstrated a chromosomal constitution of 47,XY, +21, +5q. Its pathological significance compared with Down's syndrome and hitherto reported partial trisomy 5q is discussed.

Abnormalities, Multiple

Changes in somatosensory-evoked potentials in limb lengthening. An experimental study on rabbits' tibiae.

To assess the influence of the rate and amount of distraction on the electrophysiologic function of the peripheral nerve during limb lengthening, somatosensory-evoked potential (SSEP) studies were performed on the hindlimbs of 96 rabbits. In Group I, the tibiae were lengthened 0.35 mm per day; in Group II, 0.7 mm per day; in Group III, 1.05 mm per day; and in Group IV, 1.4 mm per day. The studies were done preoperatively and then postoperatively, until six weeks in Group I, five weeks in Group II, four weeks in Group III, and three weeks in Group IV. As lengthening proceeded, the P1 (the first major positive peak) latency gradually increased, whereas the amplitude decreased. Significant amplitude changes were observed at six-weeks postsurgery in Group I, three weeks in Group II, two weeks in Group III, and one week in Group IV. Significant changes in P1 latency were observed at four weeks postsurgery in Group II, three weeks in Group III, and two weeks in Group IV. Greater percentage increases in tibial length corresponded to more marked changes in P1 latency and amplitude. The SSEP monitoring may serve as an effective tool for early detection of neurologic dysfunction during limb lengthening.

Animals

Lack of prognostic value of histopathologic parameters in Hodgkin's disease, nodular sclerosis type. A study of 123 patients with limited stage disease who had undergone laparotomy and were treated with radiation therapy.

The value of histopathologic parameters in predicting the long-term overall survival probabilities was studied in a series of 123 patients with pathologic stage IA, IB, IIA, IIB, or IIIA Hodgkin's disease, nodular sclerosis type who were treated with curative radiation therapy. The parameters that were studied included the relative proportion of atypical vs reactive cells, amount of eosinophils, presence of necrosis, degree of mitotic activity, intensity of different types of mesenchymal reactions, classification in three subtypes (ie, lymphocyte predominance, mixed cellularity, and lymphocyte depletion) or in two grades (ie, grades 1 and 2), and identification of the syncytial variant. For each parameter, the association with clinical risk factors was also analyzed. The results of this study show that there are no pathologic features that carry a significant predictive value of the overall survival.

Adolescent

Mechanism of the potentiating effect of ribavirin on the activity of 2',3'-dideoxyinosine against human immunodeficiency virus.

Ribavirin enhances the anti-human immunodeficiency virus activity of 2',3'-dideoxyinosine (ddIno) in MT-4, CEM and peripheral blood lymphocyte cells. Ribavirin causes an increase in the levels of IMP, the presumed phosphate donor for the conversion of ddIno to ddIMP by 5'-nucleotidase. Consequently, ribavirin stimulates the conversion of ddIno to its antivirally active metabolite ddATP. Ribavirin also causes a marked depletion of the guanine nucleotide pools. The increase in IMP pool levels may result from (i) a direct inhibitory effect of ribavirin 5'-monophosphate on IMP dehydrogenase (which converts IMP to XMP) and (ii) an indirect inhibition of adenylosuccinate synthetase by the decreased GTP and dGTP pools (since GTP is an obligatory cofactor in the conversion of IMP to succinyl AMP). GTP depletion plays a key role in the accumulation of IMP and the resultant higher rate of ddIno phosphorylation to ddIMP and eventually ddATP. Our findings are in agreement with the observations that guanosine and 2'-deoxyguanosine, but not 2'-deoxyadenosine, reverse (i) the stimulatory effect of ribavirin on the anti-human immunodeficiency virus activity of ddIno and (ii) the accumulation of endogenous IMP pools as well as accumulation of [3H]IMP from exogenous [3H]hypoxanthine in ribavirin-treated cells.

Biotransformation

1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) and 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) markedly potentiate the inhibitory effect of 2',3'-dideoxyinosine on human immunodeficiency virus in peripheral blood lymphocytes.

Ribavirin and EICAR are two antiviral agents that share a similar antiviral activity spectrum and are targeted at inosine 5'-monophosphate (IMP) dehydrogenase. Neither ribavirin nor EICAR inhibit the replication of human immunodeficiency virus (HIV) in peripheral blood lymphocyte cells (PBL) at subtoxic concentrations. However, both compounds markedly potentiate the anti-HIV activity of 2',3'-dideoxyinosine (DDI) in PBL cells without a marked increase of toxicity. Both the increased IMP levels and the decreased guanine nucleotide levels caused by ribavirin and EICAR may be responsible for their potentiating effect on the anti-HIV activity of DDI.

Antiviral Agents

Border separation for adjacent orthogonal fields.

Field border separations for adjacent orthogonal fields can be calculated geometrically, given the validity of some important assumptions such as beam alignment and field uniformity. Thermoluminescent dosimetry (TLD) measurements were used to investigate dose uniformity across field junctions as a function of field separation and, in particular, to review the CCSG recommendation for the treatment of medulloblastoma with separate head and spine fields.

Cerebellar Neoplasms

Finite-element modeling of the synthetic intervertebral disc.

An ideal and realistic finite-element analysis should include several factors, such as geometry (shape and size), the relative volumes of the nucleus to the anulus fibrosus, the fiber volume fraction within the anulus, and material properties. In this study, a finite-element analysis model for the disc that included these factors was developed. In addition, synthetic disc prostheses with the same specifications of geometry and material properties were manufactured. The developed model was found to be reliable and accurate when finite-element analysis results were compared with experimental synthetic disc data. The model also matched the mechanical behavior of the natural disc. This finite-element analysis model provides a tool to study the mechanical behavior of discs with varying degrees and types of injury and degeneration.

Biomechanical Phenomena

Development of a prosthetic intervertebral disc.

This article is a preliminary report of a 10-year investigation of the development of an intervertebral disc prosthesis. Spinal fusion is a method for the treatment of chronic, disabling low-back pain that does not respond to nonoperative treatments. Spinal fusion, however, has various adverse effects, and the results of spinal fusion are often unpredictable. The goal of this research project was to develop disc prostheses that have mechanical properties very similar to those of natural, normal discs. Two types of disc prosthesis, one with fiber-reinforced polyurethane and the other with multicomponent, non-fiber-reinforced polymers (C-Flex), have been designed and manufactured. The fiber-reinforced disc was made of polyurethane end-plates with A100 hardness, a homogenous nucleus with A40, and 12 layers of multidirectional (0, +45 degrees), fiber-reinforced anulus with A40 polyurethane. The design and modeling of the multicomponent polymers (non-fiber-reinforced) was made of C-Flex endplates with A90 hardness, a nucleus with A35 occupying 35% of the volume, and an anulus with 70A. Mechanical testing of these disc prostheses demonstrated similar mechanical properties to those of natural, normal discs.

Biocompatible Materials

Vocal quality factors: analysis, synthesis, and perception.

The purpose of this study was to examine several factors of vocal quality that might be affected by changes in vocal fold vibratory patterns. Four voice types were examined: modal, vocal fry, falsetto, and breathy. Three categories of analysis techniques were developed to extract source-related features from speech and electroglottographic (EGG) signals. Four factors were found to be important for characterizing the glottal excitations for the four voice types: the glottal pulse width, the glottal pulse skewness, the abruptness of glottal closure, and the turbulent noise component. The significance of these factors for voice synthesis was studied and a new voice source model that accounted for certain physiological aspects of vocal fold motion was developed and tested using speech synthesis. Perceptual listening tests were conducted to evaluate the auditory effects of the source model parameters upon synthesized speech. The effects of the spectral slope of the source excitation, the shape of the glottal excitation pulse, and the characteristics of the turbulent noise source were considered. Applications for these research results include synthesis of natural sounding speech, synthesis and modeling of vocal disorders, and the development of speaker independent (or adaptive) speech recognition systems.

Adult