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Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 721 records · Page 40Linked to original sources

Selective delivery of etoposide to intraperitoneal tissues using a new dosage format: etoposide microcrystals suspended in oil.

Rats received an intraperitoneal bolus injection of etoposide at 5 mg/kg of body weight in the form of an etoposide microcrystal suspension in oil (ETOP-OIL) or an aqueous etoposide solution. The tissue distribution was subsequently analyzed using high performance liquid chromatography. ETOP-OIL delivered significantly greater amounts of etoposide and for a longer duration to the intraperitoneal tissues such as the omentum and the spleen, whereas it delivered significantly less etoposide to the rest of the body such as the lung, the heart and the bone marrow, than the aqueous etoposide solution.

Animals↗

A comparative study of fixation techniques for type II fractures of the odontoid process.

Primary screw fixation of a Type II odontoid fracture or non-union is an attractive alternative to posterior atlanto-axial arthrodesis in that normal cervical motion can be maintained. Eight cervical cadaver spines, ranging in age from 17-90 years, were used for study. Type II fractures of the dens were created using an osteotome. Simulated fractures were fixed using one or two 3.5-mm bone screws. After testing each screw fixation technique, the screws were removed and a posterior C1-C2 brooks sublaminar wiring was performed using four 18-gauge wires with wooden blocks to simulate bone graft. No significant differences were found between bending and torsional stiffnesses for the one-screw and two-screw specimens. No significant differences were found between one- and two-screw fixation when compared with primary C1-C2 wiring in torsion. One- or two-screw fixation was as stiff as primary C1-C2 wiring in bending. One or two screws offers similar stability for fixation for a dens fracture. One- and two-screw fixation is at least as stiff as primary C1-C2 wiring in torsion and one- or two-screw fixation is stiffer than primary C1-C2 wiring in bending.

Adult↗

Nutrition care for children with special health needs: a chart review.

A random sample of 182 client charts at local agencies serving children with special needs were reviewed to identify any children at nutrition risk and determine if they had access to nutrition services. A standardized protocol was used to review data on clinical and dietary variables. The findings indicate a need for improved data collection, better use of collected data, and greater agency use of registered dietitians.

Adolescent↗

Atrial natriuretic peptide in stable and decompensated chronic obstructive pulmonary disease.

BACKGROUND: Plasma levels of atrial natriuretic peptide (ANP) are elevated in patients with chronic obstructive pulmonary disease (COPD) and may have a role in preventing oedema formation in these patients. METHODS: Plasma ANP levels were measured in 60 patients with COPD and these measurements were related to pulmonary haemodynamics, response to treatment during exacerbations, and clinical patterns of the stable disease. RESULTS: Plasma ANP levels did not correlate significantly with right atrial or pulmonary arterial pressures but did correlate significantly with both the right ventricular end diastolic volume and right ventricular wall volume measured by magnetic resonance imaging. Oxygen (2 1/min by nasal prongs for 30 minutes) did not change the mean pulmonary arterial pressure or the level of plasma ANP. In 20 patients with an acute exacerbation of COPD plasma ANP levels were higher in those with oedema (302 (185) pg/ml) than in those without oedema (87 (43) pg/ml). Oxygen given for one hour had no effect on plasma levels of ANP. However, plasma ANP levels fell over the first three days during treatment in those with oedema, the fall correlating with the change in body weight. In a further 20 stable patients with hypoxic COPD, those with hypercapnia and previous episodes of oedema had higher levels of plasma ANP (120 (50) pg/ml) than normocapnic patients with no previous oedema (54 (15) pg/ml). CONCLUSIONS: The level of ANP is high in the plasma of patients with COPD, particularly during exacerbations in those with oedema. The association of a high plasma ANP level and volume overload is shown by the fall in ANP levels with treatment of the oedema, and the correlation between levels of ANP and right ventricular end diastolic or wall volumes.

Acute Disease↗

Vitamin E treatment of tardive dyskinesia.

OBJECTIVE: The authors studied the effects of vitamin E treatment of tardive dyskinesia; earlier studies have produced contradictory results. METHOD: Twenty-eight patients with tardive dyskinesia were treated in a double-blind, parallel-group comparison study of 8-12 weeks of treatment with vitamin E (1600 IU/day) or matching placebo capsules. RESULTS: The Abnormal Involuntary Movement Scale scores of the patients treated with vitamin E improved significantly compared to the scores of the patients given placebo. CONCLUSIONS: These results support earlier findings of the efficacy of vitamin E in treating tardive dyskinesia.

Ambulatory Care↗

Developmental and molecular characterization of mutations in the Drosophila-raf serine/threonine protein kinase.

Formation of the tail region of the Drosophila larva requires the activities of the terminal class genes. Genetic and molecular analyses of these genes suggests that localized activation of the receptor tyrosine kinase torso at the posterior egg pole triggers a signal transduction pathway. This pathway, mediated through the serine/threonine protein kinase D-raf and the protein tyrosine phosphatase corkscrew, controls the domains of expression of the transcription factors tailless and huckebein. In this paper, we report the molecular and developmental characterization of mutations in the D-raf gene. We show that mutations that alter conserved residues known to be necessary for kinase activity are associated with a null phenotype, demonstrating that D-raf kinase activity is required for its role in torso signaling. Another mutation, D-rafPB26, which prematurely truncates the kinase domain shows a weaker maternal effect phenotype that is strikingly similar to the corkscrew maternal effect phenotype, suggesting that a lower amount of kinase activity decreases the terminal signaling pathway. Finally, molecular and developmental characterization of two mutations that affect the late D-raf zygotic function(s) implies a novel role for D-raf in cell fate establishment in the eye. One of these mutations, D-rafC110, is associated with a single amino acid change within the putative D-raf regulatory region, while the other, D-rafHM-7, most likely reduces the wild-type amount of D-raf protein.

Amino Acid Sequence↗

North-American twins with IDDM. Genetic, etiological, and clinical significance of disease concordance according to age, zygosity, and the interval after diagnosis in first twin.

In 224 twin pairs (132 monozygotic, 86 dizygotic, and 6 of uncertain zygosity) in whom the index twin had developed IDDM before 30 yr of age, 51 of the co-twins (38 monozygotic, 10 dizygotic, and 3 of uncertain zygosity) subsequently became diabetic. On the basis of concordance ratios, which were significantly discrepant (P < 0.01) between monozygotic and dizygotic twins, the substantial genetic role in IDDM etiology is confirmed. For the monozygotic co-twin of an IDDM case, the relative risk is significantly related to an early age at proband diagnosis (P < 0.01 for 0-4 vs. 5-9 yr of age). However, among monozygotic co-twins at any age, IDDM risk decreases as time passes after the proband diagnosis (P < 0.01 for 0-23 vs. > or = 24 mo after a proband diagnosis at 5-9 yr of age). Moreover, a structural-equation analysis suggests a profound contribution to liability (as much as 79%) from the twins' shared environment. Risk to like-sex male dizygotic co-twins is as high as that to monozygotic co-twins, significantly higher than that to like-sex female dizygotic co-twins (P < 0.005), and even higher than that to male co-twins in unlike-sex dizygotic pairs (P < 0.05). Overall, the risk to the dizygotic co-twin of a case is significantly higher (P < 0.001) than that to a non-twin sibling, as reported in the literature. The observed male excess is consistent with reported patterns of IDDM in experimental animals, and in certain circumstances in humans. Taken together, these observations suggest an important early acquired determinant of IDDM, independent of genetic determinants. On the basis of Kaplan-Meier IDDM-free survival curves, if the proband is diagnosed before 15 yr of age, the long-term risk to the co-twin is estimated at 44% (monozygotic) and 19% (dizygotic); it reaches 65% for the co-twin of a monozygotic proband diagnosed before 5 yr of age. An IDDM discordant period of no more than 3 yr was observed in 60% of the pairs destined to become concordant, offering a very brief window for intervention following the recognition of high risk.

Age Factors↗

Effect of induction cytarabine dose intensity on long-term survival in acute myelogenous leukemia: results of a randomized, controlled study.

The optimal dose and schedule of cytarabine in induction chemotherapy of newly diagnosed acute myelogenous leukemia is not established. We compared the use of cytarabine 200 mg/m2/day by continuous infusion for seven days to an intermediate-dose of cytarabine, 500 mg/m2 every 12 hours for 12 doses. Thirty-seven of 52 patients assigned to conventional-dose cytarabine achieved complete remission (71%) and the actuarial disease-free and overall survival after achieving remission were 22 +/- 16% and 31 +/- 19% respectively. Thirty-seven of 50 patients assigned to intermediate-dose cytarabine achieved remission (74%) and the actuarial disease-free and overall survival after achieving remission were 26 +/- 16% and 39 +/- 18% respectively. There were no statistically significant differences in complete remission rate, actuarial leukemia-free survival or overall survival between the groups. The most significant predictor for survival was age. Actuarial two year leukemia-free survival and overall survival for patients age > 60 were 8 +/- 15% and 20 +/- 19% respectively compared to 36 +/- 14% and 54 +/- 15% for patients age < or = 60 (P = .058 and .01, respectively). Induction regimen did not significantly affect disease free or overall survival for patients under or over age 60. We conclude that intermediate-dose cytarabine did not substantially improve results of induction for newly diagnosed acute myeloid leukemia.

Adolescent↗

The thrombolytic effect of lumbrokinase is not as potent as urokinase in a rabbit cerebral embolism model.

The purpose of the present study is to determine whether lumbrokinase has an in vivo thrombolytic effect in a rabbit cerebral embolism model. In our previous studies, we found that lumbrokinase, an extract from Korean earth worms, has a strong in vitro fibrinolytic effect without the presence of plasminogen and significant in vivo thrombolytic effects of lumbrokinase in a rat human-clot-induced cerebral embolism model. We established the cerebral embolism model in rabbits by injecting a piece of human clot into the internal carotid artery via the external carotid artery and confirmed the occlusion with angiography. Twenty one rabbits were divided into three groups and 5cc of saline, urokinase of 50,000 u/ml, and equipotent LK were injected intraarterially for 30 minutes into each group of 7 animals. Ten minutes after the end of infusion, an angiogram was performed to confirm the recanalization. Clot lysis occurred in one, six, and one animals in the saline, urokinase and lumbrokinase treated groups respectively. With regard to its in vitro effect, lumbrokinase is not as potent in vivo. Further investigation should be performed to determine the cause of its weakened in vivo effect and to develop a method to potentiate it.

Animals↗

Asian-born scientists and engineers: their immigration flow and labor market adjustment.

"This paper examines the flow of Asian-born scientists and engineers and their labor market adjustment. First, main elements to affect their immigration flow are described: supply, demand, and institution....The scarcity of domestic workers is the most important factor affecting demand of immigration. Institution, such as immigration policies, is another element to influence the immigration flow....Second, by using the 1980 U.S. Census data set, their labor market adjustment is explored in terms of hourly wages. Compared to the native-born white, there is no evidence that Asian-born scientists and engineers receive lower wages or lower return on human capital."

Americas↗

Effect of loading frequency on response of the spine to lumbar posteroanterior forces.

OBJECTIVE: The purpose of this investigation was to study the spinal deformations produced by applying a force to a lumbar vertebra and to compare the deformation responses at three different loading rates. SETTING: The study was conducted in a laboratory setting using a mechanical device to simulate the manipulative procedure being studied. SUBJECTS: Twelve volunteers (mean age 28.1 yr) formed a convenience sample for testing. All subjects had no significant history of low back pain. INTERVENTIONS: During loading the displacements of the skin were measured at the point of loading, as well as over the spinous processes of L1, T11, T8, and S1 and 30 mm caudad to S1. The loading rates were 1.0 Hz, 0.5 Hz and a very slow "quasistatic" rate. The order of presentation of the loading rates was systematically varied between subjects to minimize the effect of order on the responses. Between 20 and 100 N, the force-displacement relations were highly linear and were characterized by the coefficients of the equation of the line of best fit. MAIN RESULTS: At all three loading rates there were displacements throughout the entire region studied. Changing from quasistatic loading to cyclical loading produced a significant reduction in displacements. CONCLUSIONS: This study found that when a force was applied over L3 there was generalized movement of the whole lumbar and lower thoracic spine. Therefore, a diversity of tissues would be expected to contribute to the resistance to lumbar posteroanterior movements.

Adult↗

Ablation rates and surface ultrastructure of 193 nm excimer laser keratectomies.

PURPOSE: To determine whether photorefractive keratectomy can be performed at lower energies than are currently employed in clinical trials. METHODS: Fresh pig corneas were ablated using a clinical excimer laser to study the effects of various energy densities (100-200 mJ/cm2) and beam diameters on ablation rates and on the surface ultrastructure of the ablated cornea. RESULTS: A 20-mJ increase in energy density was associated with a 0.03 micron per pulse increase in the ablation rate. A nearly linear increase in the pseudomembrane thickness occurred with increasing energy densities (r2 = 0.83) or decreasing ablation area diameter (r2 = 0.86). CONCLUSIONS: Our findings suggest that fluences less than those currently used in clinical trials (160-180 mJ) are capable of ablating tissue while producing thinner electron-dense pseudomembranes on the corneal surface. The relationship between pseudomembrane thickness and clinical factors such as reepithelialization and postoperative haze remains to be determined. Operating at lower fluences does have the advantages of allowing larger diameter ablations, reducing possible shockwave damage, and reducing the maintenance requirements for the laser.

Animals↗

[Evaluation of the effect of the sodium hyaluronate ophthalmic solution on tear film stability--non-contact specular microscopic evaluation].

Sodium hyaluronate solution is known to relieve various dry eye symptoms by suppressing the breakup of the preocular tear film. Using tear film stability as a parameter, we examined in 12 volunteers the time and concentration-dependent effects of sodium hyaluronate on their short precorneal tear film breakup time (BUT, 10 sec. or less) at a low tear volume (15 mm or less by using the phenol red thread test). Each subject underwent four separate study periods, receiving one of the following four ophthalmic solutions during each period: 0.05, 0.1, 0.3% w/v sodium hyaluronate (molecular weight, about 1,000,000) or the vehicle alone. BUT was measured non-invasively using a non-contact specular microscope before and 5, 15, 30, 60, 120, and 180 minutes after drug application. While BUT was not significantly prolonged after instilling either the vehicle or 0.05% solution, it was significantly increased at all times after applying either 0.1% or 0.3% solution, as compared to preinstillation. These results indicate that sodium hyaluronate solutions at concentrations of at least 0.1% can be effective in alleviating symptoms of dry eye.

Adult↗

Design, synthesis, and biological evaluation of DNA sequence and minor groove selective alkylating agents.

The syntheses of oligoimidazolecarboxamido analogues of distamycin wherein the N-terminus contains either a benzyl-mustard 8 or chlorambucil moiety 9-11 are reported. Based on data from an ethidium displacement assay and CD studies, these compounds, along with the N-benzoyl mustards 6 and 7, were shown to have increased acceptance of GC-rich sequences over distamycin. Compounds 8-11 which contain an electron-donating group (sigma < 0) para to the bischloroethylamino moiety, were found to have significantly enhanced reactivity with DNA compared to the benzoyl mustards 6 and 7. Through dialysis experiments, the benzyl and chlorambucil mustards were shown to alkylate calf thymus DNA more readily than the benzoyl mustards, presumably due to destabilization of the aziridinium intermediate by the electron-withdrawing (sigma > 0) carboxamido group of the benzoyl compounds. Compounds 8-11 were found to alkylate guanine-N7 in the major groove, while compounds 6 and 7 did not, suggesting that they may have different modes of DNA interaction. Mustards 8-11 were also more efficient than 6 and 7 at producing DNA interstrand cross-links in isolated DNA. In general, for these compounds, the cytotoxicity against human chronic myeloid leukemia K562 cells and the panel of human tumor cell lines of the National Cancer Institute increased with the number of imidazole moieties. The IC50 values of compounds 7 and 8 were similar, even though the latter compound was at least 100-fold more efficient at forming DNA cross-links in isolated DNA. Similarly, compounds 9-11 were less cytotoxic than 6 and 7, although they were more efficient cross-linkers in isolated DNA. A direct comparison of the three imidazole-containing benzoyl mustard 7 with the corresponding chlorambucil-containing 11 for their ability to form interstrand cross-links in cells revealed that the former compound showed no cross-linking even at doses in excess of the IC50, whereas the latter produced extensive cross-linking. This further suggests that these compounds exert their biological activity through different mechanisms. It is proposed that the aromatic moiety of compounds 8-11, which bind to the minor groove, may be able to intercalate between GC base pairs and the protruding bischloroethylamino group would be positioned to alkylate and cross-link at guanine-N7 sites in the major groove. However, the benzoyl mustards, which have a rigid amino linkage between the imidazole and aromatic-mustard moieties, do not have the flexibility to intercalate into the DNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkylating Agents↗