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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

The effect of exposure to nicotine, carbon monoxide, cigarette smoke or cigarette smoke condensate on the mutagenicity of rat urine.

Cigarette smokers have been reported to void urine which is more mutagenic than that voided by non-smokers, but the specific urinary mutagen(s) have not been identified. Since mechanistic studies are best performed in animal models, the objective of this study was to determine if a model to study the role of cigarette smoke and its components in urinary mutagenicity could be developed in rats. XAD-2 resin was used to concentrate the urine and the microsuspension modification of the Ames test used to quantify mutagenicity. Nicotine administered by intraperitoneal injection at 0.8 mg/kg (the maximum tolerated dose) or inhalation of carbon monoxide for 14 days at the maximum tolerated dose (1800 ppm, resulting in 68% carboxyhemoglobin) did not increase urinary mutagenicity. Cigarette smoke condensate (CSC) prepared by electrostatic precipitation of mainstream smoke increased urinary mutagenicity at doses of 100 and 200 mg/kg when administered acutely by either i.p. injection or gavage, verifying that the assay system was capable of detecting cigarette smoke-related mutagens in the urine. However, cigarette smoke administered by the appropriate route of exposure, nose-only inhalation, for 1, 7, 14 or 90 days (1 h per day) did not increase urinary mutagenicity. The smoke concentration administered was at or near the maximum tolerated dose as evidenced by carboxyhemoglobin concentrations of approximately 50%, and of 10% or more weight loss in exposed animals. Thus, although cigarette smoke condensate is mutagenic in vitro and mutagenic urine was observed when rats were given high doses of CSC by inappropriate routes of administration, acute or subchronic inhalation exposure to the maximum tolerated dose of whole cigarette smoke did not increase urinary mutagenicity in rats. These results indicate that the rat may be an inappropriate model to study urinary mutagenicity following the inhalation of tobacco smoke.

Administration, Inhalation

Precooling prevents overheating of subcutaneous fat in the use of RF capacitive heating.

The usefulness of precooling subcutaneous tissue in the hyperthermic treatment of deep-seated human tumors with capacitive application of radio-frequency (RF) was investigated. A capacitive hyperthermia unit operated at 8 MHz of radiofrequency was used to heat deep-seated human tumors. The electrode surfaces were covered with flexible vinyl sheets and the space between the electrode and the vinyl sheets perfused with 0.4% saline. The temperature of the saline was controlled by circulating the saline through built-in heat exchangers. The depth of heating was controlled by pairing electrodes of different diameters. When subcutaneous fat was less than 1 cm thick, various deep-seated tumors could be heated to a therapeutic temperature without significant discomfort in the subcutaneous tissue as long as the skin was properly cooled with the cold saline bolus. However, the same cooling method could not prevent the occurrence of pain in subcutaneous tissue in obese patients. The pain usually developed when the temperature of subcutaneous fat 1-2 cm below the skin surface exceeded 42 degrees C. We observed that cooling the human skin surface with 10 degrees C bolus for 20 min could substantially lower the temperature of fat as deep as 2.0-2.5 cm. Therefore, when the subcutaneous tissue was precooled with 10 degrees C saline for 20 min or longer before heating, it was possible to prevent successfully the overheating of subcutaneous fat as thick as 2.0-2.5 cm and to raise the temperature of deep-seated tumors to therapeutic levels.

Adipose Tissue

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

A preliminary study of mechanically stress-induced changes in the extracellular matrix of the canine intervertebral disc.

The intervertebral discs of a young (age, 3 years) and an old (age, 8 years) dog were isolated as motion segments and cyclically stressed in physiologic nondestructive axial compression loads. Chemical analysis of the matrix of the annulus fibrosus revealed a shift in proteoglycan molecular size from larger to smaller moieties for the older dog but not for the younger. These preliminary results may indicate an age-related inability of the disc to tolerate cyclic stress.

Aging