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Biomedical subjects

M L Lee

Publications and source records attributed to M L Lee.

At least 91 records · Page 5Linked to original sources
PubMed1997

Quantitative analysis of exogenous peptides in plasma using immobilized enzyme cleavage and gas chromatography-mass spectrometry with negative ion chemical ionization.

A method is presented for the analysis of peptides in plasma at picomole to femtomole levels. Peptides are isolated from plasma by solid-phase extraction, the peptide of interest is purified by reversed-phase high-performance liquid chromatography (HPLC) and selectively digested using immobilized trypsin or chymotrypsin to yield specific di- or tripeptides. These di- and tripeptides are esterified using heptafluorobutyric anhydride, alkylated with pentafluorobenzyl bromide, then quantified by gas chromatography-mass spectrometry with negative ion chemical ionization. This method has been evaluated for a model synthetic heptapeptide, using a deuterium labeled analog as an internal standard. The half-life of the heptapeptide in human plasma was found to be 2 min. Extraction efficiencies of a tritiated peptide of similar size to the heptapeptide, [3H]DSLET, from plasma using either C18 or strong cation-exchange columns were 85+/-3 and 70+/-2%, respectively. Quantitation of fragments from the heptapeptide indicated that the analysis was linear from 1-50 ng of the heptapeptide per ml of plasma. This method was subsequently employed for pharmacokinetic studies of the biologically active peptide Met-enkephalin-Arg-Gly-Leu, where linearity was obtained from 50 to 1000 ng/ml in rat plasma. This method demonstrated negligible side reaction by-products due to autolysis, and has potential for extensive use given the wide availability of gas chromatography-mass spectrometry.

Animals↗
PubMed1997

Prevalence of diabetes mellitus and impaired glucose tolerance in Aborigines and Chinese in eastern Taiwan.

The aim of this study was to determine the prevalence of diabetes mellitus and impaired glucose tolerance (IGT) in three different ethnic groups in eastern Taiwan. The study was performed among Han Chinese, aboriginal Ami and aboriginal Atayal in six rural villages. Inhabitants aged 40 years and over were invited to participate. A 75-g oral glucose tolerance test (OGTT) was used as suggested by the World Health Organization (WHO) for population screening purposes. WHO criteria were used for determining the results. A total of 1013 adults (460 men and 553 women) were examined with a response rate of 62.1%. There were no significant differences in sex, age and history of diabetes between responders and non-responders. The age-adjusted prevalence of diabetes was 11.0% (9.8% in men and 12.3% in women) in the Chinese, 9.1% (12.1% in men and 7.4% in women) in the Amis, 10.8% (11.5% in men and 9.4% in women) in the Atayal and 9.9% (11.5% in men and 8.5% in women) for the two aboriginal groups together. Although sex differences in prevalence of diabetes were not statistically significant, it seems that diabetes was slightly more prevalent in Chinese women than in Chinese men (12.3 versus 9.8%). Nonetheless, the prevalence rate of diabetes was somewhat higher in the aboriginal males than in the aboriginal females (12.1 versus 9.8% for Ami and 11.5 versus 10.7% for Atayal). The prevalence of IGT was 7.2, 8.5, 10.8 and 9.7% for the Chinese, Amis, Atayal and the two aboriginal groups, respectively. There were no substantial differences in the prevalence of diabetes and IGT among these three ethnic groups. Environment, rather than ethnicity, was more likely the predominant factor. It was found that the prevalence of diabetes in this study was about twice as high as that reported in a 1987 survey in Taiwan. The discrepancy may be due to different screening methods and assessment periods.

Adult↗
PubMed1997

The utility of patient age in evaluating prostate cancer.

The utility of age in examining patients for prostate cancer was assessed. Of the 462 patients in the study, 138 had prostate cancer. The age distribution of the patients with cancer was similar to that found in patients with prostate cancer in the US population, and a correlation between age and the serum prostate-specific antigen (PSA) value was noted (r = .4, P < .002). Selection of reference intervals had a significant effect on test performance. Using an interval of 0 to 4.0 ng/mL, sensitivity of the PSA assay was 90% overall and varied from 78% (patients aged 50-59 years) to 94% (patients aged 70-79 years). In contrast, age-adjusted reference ranges yielded corresponding sensitivities of 84%, 78%, and 88%. With a single, fixed reference range, specificity decreased with advancing patient age (P < .001). This trend was eliminated by adjusting the cutoff in different age groups. In addition, age-adjusted reference ranges improved specificity by 10%, and by using the results of examination of a biopsy specimen as the "gold standard," the total number of patients classified correctly by PSA increased from 226 to 250 (49%-54%). For staging before treatment, patient age, clinical stage, and Gleason score were combined to yield a single probability estimate for organ-confined disease (P < .001). The use of age-adjusted reference ranges is supported by this study, which demonstrates that assay efficiency and specificity improve and sensitivity, although decreased overall, becomes more uniform across age groups. In this patient population, age was useful in determining the probability of organ-confined prostate cancer. Use of this model in clinical decision making should await evaluation in a prospective trial.

Age Distribution↗
PubMed1997

Biomechanical evaluation of current patella fracture fixation techniques.

OBJECTIVE: To compare the mechanical effectiveness of three different techniques for stabilization of transverse fractures of the patella. DESIGN: Cadaveric knees were used to model acute fractures of the patella. To test three treatment techniques in pairs of knees, specimen pairs were assigned randomly to a set of predetermined treatment pairs so as to provide equal numbers of paired and unpaired data sets. Results then were analyzed using a two-way analysis of variance. SETTING: The treatment techniques used are widely applicable in the clinical setting for the treatment of transverse fractures of the patella. No specialized equipment or training is required for the general or subspecialized orthopaedic surgeon. PATIENTS/PARTICIPANTS: None. INTERVENTIONS: Fractures were created in eighteen knees (nine pairs) and repaired by one of three techniques: (a) modified tension band (AO technique); (b) two parallel 4.5-millimeter interfragmentary lag screws; or (c) a new technique using four-millimeter cannulated lag screws with a tension band wired through the screws. MAIN OUTCOME MEASURES: In mechanical testing, the amount of interfragmentary separation in simulated knee extension and the maximum load to failure at 45 degrees of flexion were measured. RESULTS: Fractures stabilized with a modified tension band were found to displace significantly more than those fixed with screws alone or screws plus a tension band in simulated knee extensions (p < 0.05). The fractures fixed with the cannulated screws plus the tension band failed at higher loads (mean = 732 newtons) than those stabilized with screws alone (mean = 554 newtons, p = 0.06) or those with a modified tension band (mean = 395 newtons, p < 0.05). CONCLUSIONS: Combining interfragmentary screw fixation with the tension band principle appears to provide improved stability over the modified tension band or screws alone for transverse patella fractures. Cannulated screws allow for simple, reliable addition of a tension band to screw fixation.

Aged↗
PubMed1997

Use of intravenous immunoglobulin to prevent or treat infections in persons with immune deficiency.

Intravenous immunoglobulin (IVIG) concentrates were originally developed as replacement therapy for individuals with primary deficiencies of the immune system. However, in various well-designed, controlled clinical trials, the ability of IVIG to prevent and possibly treat infections in patients with secondary immune deficiencies has also been considered. In this review, we briefly consider these different applications and suggest whether the data are sufficient to employ IVIG in these clinical settings.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Analysis of overdispersed count data by mixtures of Poisson variables and Poisson processes.

Count data often show overdispersion compared to the Poisson distribution. Overdispersion is typically modeled by a random effect for the mean, based on the gamma distribution, leading to the negative binomial distribution for the count. This paper considers a larger family of mixture distributions, including the inverse Gaussian mixture distribution. It is demonstrated that it gives a significantly better fit for a data set on the frequency of epileptic seizures. The same approach can be used to generate counting processes from Poisson processes, where the rate or the time is random. A random rate corresponds to variation between patients, whereas a random time corresponds to variation within patients.

Anticonvulsants↗
PubMed1997

Breakdown and rebuilding of myofibrils in cultured adult cardiac muscle cells.

The myofibrils of adult rat cardiac muscle cells in culture break down and later reorganize into mature myofibrils. The myofibrillar breakdown and reorganization processes have been investigated with electron microscopical and immunocytochemical studies. The immunocytochemical studies included antibodies to actin, myosin, titin, and alpha-actinin. In addition, rhodamine-labeled phalloidin has been used. These studies revealed that the myofibrils were disorganized into amorphous and/or other forms during breakdown process. Some of these myofibrils undergo degradation and finally extrusion through exocytosis. The reorganization of myofibrils takes place mainly with the participation of the existing myofibrillar proteins in myocytes. This remyofibrillogenesis showed the emergence of punctate alpha-actinin from the existing amorphous alpha-actinin along with the differentiation of titin periodicities, which remained attached to the alpha-actinin structures. The punctate alpha-actinin later differentiated into periodicities, forming Z-lines. The periodicities of actin were differentiated from the amorphous actin and associated with the Z-lines, giving rise to titin, alpha-actinin, and actin complexes. Later, myosin filaments became associated with these complexes, forming sarcomeres where other myofibrillar proteins participated in the formation of mature myofibrils. The temporal sequence of differentiation of periodicities of certain myofibrillar proteins varied among different myocytes and within a single myocyte. The dynamic role of adult cardiac myocytes in the reconstruction of myofibrils is a remarkable phenomenon, which stabilizes adult cardiac muscle cells in long-term culture.

Animals↗
PubMed1996

Remodelling of adult cardiac muscle cells in culture: dynamic process of disorganization and reorganization of myofibrils.

The myofibrils of adult rat cardiac muscle cells in long-term culture initially break down and later reassemble into mature myofibrils. The objective of this study is to examine the disorganization process of myofibrils and to determine how disorganized myofibrillar proteins, myosin, titin, actin, and alpha-actinin are reorganized into mature myofibrils in adult cells. After dismantlement of myofibrils during initial culture period (24-72 h), myofibrillar proteins became disorganized into amorphous form. These proteins later were observed in vesicular, amorphous, and nonstriated fibrillar forms. Some vesicular structures, containing mainly myosin, titin, alpha-actin, and alpha-actinin were observed on the outer surfaces of the cell and outside the cell body. Such vesicles containing F-actin were rare. Punctate structures of alpha-actinin emerged from the pre-existing amorphous alpha-actinin along with the appearance of mostly titin periodicities. The periodicities of alpha-actinin later became prevalent, followed by the appearance of periodicities of actin. alpha-actinin provided an initiation point on which titin and actin became associated, forming titin-associated I-Z-I structures. Titin traversed the I-bands on either side of the Z-line. The phalloidin-stained I-Z-I structures bound to antibodies to muscle specific sarcomeric proteins (titin, alpha-actin, alpha-actinin). The differentiation of myosin periodicities lagged behind those of titin, alpha-actinin, and actin although presarcomeric structures of immunolabelled titin and myosin were very closely linked in their distributions in the formative myofibrils. Variations in the temporal sequence of emergence of periodicities of alpha-actinin and myosin were observed among certain myocytes. Also observed was the variation of the temporal sequence of emergence of titin and actin periodicities among different myocytes and within a single myocyte. Even in the late stage of culture (30 days), when the cell body was packed with myofibrils, the myocytes contained remnants of amorphous myofibrillar proteins.

Actinin↗
PubMed1996

Can a specialty society educate its members to think differently about clinical decisions? Results of a randomized trial.

OBJECTIVE: Measure the effect of specialty society-developed continuing medical education (CME) on clinical decision making. DESIGN: Randomized controlled trial. SETTING: National sample of neurologists. PARTICIPANTS: Of 492 neurologists randomly selected from an ongoing American Academy of Neurology CME program, 248 were randomized to receive a mailed CME course, and 244 did not receive it. INTERVENTION: A mailed educational course on movement disorders, developed by the specialty society, containing information on diseases and practice recommendations with illustrative case presentations. MEASUREMENTS AND MAIN RESULTS: We assessed adherence to 16 practice recommendations on disease detection, diagnostic test use, and treatments by mailed survey sent to all subjects 4.5 months after the intervention group received the course (73% response rate). The survey contained detailed clinical scenarios to measure self-reported clinical decision making and short open-ended questions to measure factual knowledge. More intervention participants (up to 2.6 times more) than control subjects reported clinical decision making adherent to 9 of the 16 recommendations (p < .05). For 4 of the other 7 recommendations, adherence exceeded 85% in both groups. Within the intervention group, neurologists who read the educational course were 2 to 6 times more likely to be adherent than neurologists who did not. The intervention group had better factual knowledge than control subjects in six of seven areas (p < .01). CONCLUSIONS: This educational course improved neurologists' reported decision making. Specialty society-developed CME that utilizes a similar format may enhance the effectiveness of mailed CME information to improve physicians' approach to clinical decisions.

Decision Making↗
PubMed1996

Congenital recessive ichthyosis unlinked to loci for epidermal transglutaminases.

Congenital recessive ichthyosis has a broad range of clinical presentations, which may be considered a spectrum of phenotypes with classic lamellar ichthyosis at one pole and classic congenital ichthyosiform erythroderma at the other. The identification of mutations in the transglutaminase-1 gene as a cause of lamellar ichthyosis implicates transglutaminases in other congenital recessive ichthyoses. We investigated two multiplex families with clinical manifestations between the two poles for linkage to the transglutaminase-1 locus on chromosome 14. Strongly negative lod scores prompted a search for linkage to two other epidermally expressed transglutaminases, transglutaminase-2 and transglutaminase-3, on chromosome 20. No evidence for linkage was found. These data confirm the hypothesis that the congenital recessive ichthyoses are genetically heterogeneous and in two families exclude two other transglutaminases that could be considered as candidate loci for at least some of the nonlamellar recessive ichthyoses.

Child↗
PubMed1996

Effects of intravenous immunoglobulin on muscle weakness and calcium-channel autoantibodies in the Lambert-Eaton myasthenic syndrome.

Intravenous immunoglobulin improves many antibody-mediated autoimmune disorders, but its mode of action is unknown. We investigated its effects on muscle strength and on the serum titer of the calcium-channel autoantibodies that are likely to be pathogenic in the Lambert-Eaton myasthenic syndrome (LEMS). In a randomized, double-blind, placebo-controlled crossover trial, serial indices of limb, respiratory, and bulbar muscle strength and the serum titer of calcium-channel antibodies in nine patients were compared over an 8-week period, using the area-under-the-curve approach, following infusion on two consecutive days of immunoglobulin at 1 g/kg body weight/day (total dose 2.0 g/kg body weight) or placebo (equivalent volume of 0.3% albumin). Calcium-channel antibodies were measured by radioimmunoassay using 125I-omega-conotoxin MVIIC. Direct anti-idiotypic actions of immunoglobulin were tested in this assay. Immunoglobulin infusion was followed by significant improvements in the three strength measures (p = 0.017 to 0.038) associated with a significant decline in serum calcium-channel antibody titers (p = 0.028). Improvement peaked at 2 to 4 weeks and was declining by 8 weeks. Mean serum titers were unchanged at 1 week, however, and direct anti-idiotypic neutralization by immunoglobulin was not demonstrable in vitro. We conclude that immunoglobulin causes a short-term improvement in muscle strength in LEMS that probably results from the induced reduction in calcium-channel autoantibodies. The reduction is not due to a direct neutralizing action of the immunoglobulin, but a delayed anti-idiotypic action cannot be excluded. Improvement following intravenous immunoglobulin in other autoantibody-mediated disorders may similarly be associated with decline in levels of pathogenic autoantibodies.

Adolescent↗
PubMed1996

Effect of oxidative insult on young and adult cardiac muscle cells in vitro.

The effect of hydrogen peroxide on cultured neonatal and adult cardiac myocytes was investigated. On neonatal cardiac myocytes the effect was very pronounced at a low concentration (0.03 mM), whereas the adult cardiac myocytes were resistant to the same concentration of H2O2. Dividing neonatal cardiac myocytes were more susceptible to H2O2 insult than the non-dividing adult cardiac myocytes. At a concentration of 0.1 mM H2O2, the neonatal cardiac myocytes were significantly damaged compared with the adult cardiac myocytes. Cardiac muscle cells from neonatal and adult hearts at high density culture were more tolerant to the oxidative insult by H2O2 than cells in low density culture. The damaging effect of H2O2 was very selective on F-actin in neonatal and adult cardiac muscle cells. The effect of H2O2 on myosin, titin, alpha-actinin, desmin or tubulin was not pronounced. Microscopical studies suggested a more marked protection by catalase than by glutathione reductase in the neonatal cells.

Amitrole↗
PubMed1996

Kenny syndrome: case report and literature review.

A 34-month-old girl presented with a clinical picture of Kenny syndrome. The clinical manisfestations included growth retardation, persistent open anterior fontanelle, prominent forehead, mid-facial dysplasia, hypocalcemic tetany and characteristic radiologic skeletal abnormalities. Serum levels of immunoreactive parathyroid hormone (PTH) remained inappropriately low during hypocalcemic episodes in the neonatal period; indicating that hypocalcemia was a consequence of the hypoparathyroid state. This is the first reported case of Kenny syndrome in Taiwan. The literature on the pathogenesis, etiology and genetic basis of this disorder is reviewed in this paper.

Abnormalities, Multiple↗