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Biomedical subjects

M L Lee

Publications and source records attributed to M L Lee.

At least 19 recordsLinked to original sources

Patient-perceived impact of resective epilepsy surgery.

OBJECTIVE: To evaluate the patient-perceived impact of resective epilepsy surgery, a key outcome to consider in evaluating such a highly invasive, elective procedure. METHODS: Impact measures obtained from 396 patients in a multicenter cohort study of resective epilepsy surgery included (1) willingness to undergo surgery if that decision could be made again and (2) the overall impact of surgery on the patient's life. Predictors of impact were analyzed using multivariate ordinal logistic regression. RESULTS: Of study participants, 73.8%, 77.4%, and 75.5% would definitely undergo surgery again and 78.2%, 80.2%, and 79.1% reported a very strong or strong positive overall impact of surgery at 3, 12, and 24 months. Multivariate ordinal logistic regression showed that seizure freedom predicted more positive perceptions at 3, 12, and 24 months (all p < 0.04). Becoming employed was uniquely associated with willingness to undergo surgery again and with overall impact at 24 months (all p < 0.05), but only a net 7% of the cohort improved their employment status. Right-sided resection (at 12 and 24 months, p < 0.005) and female gender (at 3 and 12 months, p = 0.006) were each positively associated with perceived overall impact. CONCLUSIONS: Most epilepsy surgery patients report a positive overall impact of the procedure on their lives and a high willingness to undergo surgery again if that choice could be made. Seizure-free individuals express consistently more positive perceptions of the procedure. Findings suggest that it is important to make early efforts to reintegrate epilepsy surgery patients into employment.

Adolescent↗

Planar thin film device for capillary electrophoresis.

Hollow tubular microfluidic channels were fabricated on quartz substrates using sacrificial layer, planar micromachining processes. The channels were created using a bottom-up fabrication technique, namely patterning a photoresist/aluminum sacrificial layer and depositing SiO(2) over the substrate. The photoresist/aluminum layer was removed by etching first with HCl/HNO(3), followed by etching in Nano-Strip, a more stable form of piranha (H(2)SO(4)/H(2)O(2)) stripper. Rapid separation of fluorescently labeled amino acids was performed on a device made with these channels. The fabrication process presented here provides unique control over channel composition and geometry. Future work should allow the fabrication of highly complex and precise devices with integrated analytical capabilities essential for the development of micro-total analysis systems.

Acids↗

A Bayesian approach to the assessment of inhibitor risk in studies of factor VIII concentrates.

The assessment of inhibitor risk is a crucial component in the clinical development of new and modified factor VIII (FVIII) preparations. There has been a recent discussion about the design of studies and the assessment of inhibitors and inhibitor risk in such studies at a recent FDA-sponsored FVIII Inhibitor Workshop, and new requirements for the success of these trials have been proposed to evaluate inhibitor data based on the use of an upper 95% confidence bound. We review the consequences of these requirements and demonstrate that for any product to succeed, it must have an extremely low underlying risk of inhibitor development. Furthermore, several existing commercially available FVIII products with an excellent safety record would not necessarily pass these endpoints. As a result, we propose an alternative set of acceptance criteria based on a Bayesian statistical paradigm. This approach is based on the determination of a probability that the product in question actually has an inhibitor risk below some pre-set limit, a concept that we believe is more intuitive than the traditional confidence interval method. We show that all existing products would pass this approach, but a product (Bisinact) with known inhibitor risk would not.

Bayes Theorem↗

Effects of testosterone replacement in human immunodeficiency virus-infected women with weight loss.

The objective of this study was to determine whether physiological testosterone replacement increases fat-free mass (FFM) and muscle strength and contributes to weight maintenance in HIV-infected women with relative androgen deficiency and weight loss. Fifty-two HIV-infected, medically stable women, 18-50 yr of age, with more than 5% weight loss over 6 months and testosterone levels below 33 ng/dl were randomized into this double-blind, placebo-controlled trial of 24-wk duration. Subjects in the testosterone group applied testosterone patches twice weekly to achieve a nominal delivery of 300 mug testosterone over 24 h. Data were evaluable for 44 women. Serum average total and peak testosterone levels increased significantly in the testosterone group, but did not change in the placebo group. However, there were no significant changes in FFM (testosterone, 0.7 +/- 0.4 kg; placebo, 0.3 +/- 0.4 kg), fat mass (testosterone, 0.3 +/- 0.7 kg; placebo, 0.6 +/- 0.7 kg), or body weight (testosterone, 1.0 +/- 0.9 kg; placebo, 0.9 +/- 0.8 kg) between the two treatment groups. There were no significant changes in leg press strength, leg power, or muscle fatigability in either group. Changes in quality of life, sexual function, cognitive function, and Karnofsky performance scores did not differ significantly between the two groups. High-density lipoprotein cholesterol levels decreased significantly in the testosterone group. The patches were well tolerated. We conclude that physiological testosterone replacement was safe and effective in raising testosterone levels into the mid to high normal range, but did not significantly increase FFM, body weight, or muscle performance in HIV-infected women with low testosterone levels and mild weight loss. Additional studies are needed to fully explore the role of androgens in the regulation of body composition in women.

Adolescent↗

Ulnar neuropathy at the elbow: follow-up and prognostic factors determining outcome.

OBJECTIVE: To determine the outcome in patients with ulnar neuropathy at the elbow (UNE) treated surgically or conservatively, and the prognostic value of clinical, sonographic, and electrophysiologic features. METHODS: After a median follow-up of 14 months, 69 of 84 patients initially included in a prospective blinded study on the diagnostic value of sonography in UNE were re-evaluated. The patients underwent renewed systematic clinical and sonographic examination. Patients were scored as having a poor (stable or progressive symptoms) or favorable (complete remission of symptoms or improvement) outcome. RESULTS: Of the 74 initially affected arms, 12 (16%) had a complete remission, 21 (28%) improved, 25 (34%) remained stable, and 16 (22%) had progression. Surgically treated patients (28 arms) had a more favorable outcome than those treated conservatively (p = 0.03). After surgery, the mean ulnar nerve diameter decreased from 3.2 to 2.9 mm (p = 0.03), while this was not seen after conservative treatment. Multiple logistic regression analysis showed that more outspoken nerve enlargement found during sonography at the time of the diagnosis was associated with a poor outcome (OR: 2.9, p = 0.009). Furthermore, the presence of a motor conduction block (OR: 0.2, p = 0.03) and motor velocity slowing across the elbow (OR: 0.1, p = 0.01) were associated with a favorable outcome. CONCLUSION: More pronounced ulnar nerve thickening at the time of the diagnosis is associated with poor outcome at follow-up, especially in conservatively treated cases, while electrodiagnostic signs of demyelination on testing indicate favorable outcome.

Adult↗

A randomized, double-blind, placebo-controlled pilot study of i.v. immune globulins in combination with i.v. methylprednisolone in the treatment of relapses in patients with MS.

BACKGROUND: Some patients with multiple sclerosis (MS) do not show a clear improvement of acute relapses after treatment with intravenous methylprednisolone (IVMP). We compared the efficacy of the combination of intravenous immunoglobulins (IVIg) and IVMP with the standard treatment of IVMP alone in promoting recovery from moderate to severe acute relapses in MS. METHODS: Patients with clinically definite MS having a relapse with at least a one point increase in Kurtzke's expanded disability status scale (EDSS) in comparison to the preattack EDSS were randomized to IVMP-IVIg or IVMP-placebo treatment. The primary outcome criterion was the EDSS grade at four weeks. A preplanned interim analysis was performed after inclusion of 19 consecutive MS patients to evaluate the sample size necessary for a larger trial. FINDINGS: Both groups had improved one point on the EDSS four weeks after start of treatment (P = 0.81) and one of the stopping rules of the interim analysis was fulfilled. There were also no differences in secondary outcomes: EDSS at eight and 12 weeks, time to improve > or = 1 EDSS points, difference in Scripps score and ambulation index. Five patients in the IVMP-IVIg group and two in the IVMP group had a new relapse in the six month follow-up. INTERPRETATION: Our study could not show superiority of IVMP-IVIg in the treatment of moderate to severe acute relapses in MS.

Adult↗

Dentigerous cyst of the maxillary sinus in a child.

Dentigerous cyst in maxillary sinus, especially in children, is uncommon in Malaysia. Few cases of dentigerous cyst in maxillary sinus in children have been reported in the medical literature. According to Tay AB et al, dentigerous cyst was accounted for 2.3% of the 20 most common diagnosed oral tumors in Singapore form year 1993--1997. This report illustrates a case of the dentigerous cyst in the maxillary sinus, resulting in significant facial swelling, which was managed by endoscopic marsupialization of the cyst.

Child↗

A cohort study of possible risk factors for over-reporting of antihypertensive adherence.

BACKGROUND: The identification of poor medicinal adherence is difficult because direct observation of medication use is usually impractical. Up to 50% of individuals on chronic therapies may not be taking their medication as prescribed. This study is one of the first to explore possible risk factors for over-reporting of antihypertensive adherence using electronic medication monitoring. METHODS: The adherence of 286 individuals on single-drug antihypertensive therapy in a large managed care organization was electronically monitored for approximately three months. Questionnaires on socioeconomic background, adherence to therapy, health beliefs, and social support before and after adherence monitoring were completed. Over-reporting of antihypertensive adherence was assessed by comparing the self-reported frequency of noncompliance with that determined from electronic dosing records. Risk factors for over-reporting were identified by contingency table analysis and step-wise logistic regression. RESULTS: Although only 21% of participants acknowledged missing doses on one or more days per week, electronic monitoring documented nonadherence at this or a higher level in 42% of participants. The following variables were associated with over-reporting: >1 versus 1 daily dose (OR = 2.58; 95% CI = 1.50-4.41; p =.0006), lower perceived health risk from nonadherence (OR = 1.35; 95% CI = 1.10-1.64; p =.0035), and annual household income of <15,000 dollars versus >30,000 dollars (OR = 2.64; 95% CI = 1.13-6.18; p =.025). CONCLUSIONS: Over-reporting of adherence may be affected by factors related to dosing frequency, health beliefs and socioeconomic status. This topic deserves further investigation in other patient populations to elucidate possible underlying behavioral explanations.

Adolescent↗

Developments in ion mobility spectrometry-mass spectrometry.

Ion mobility spectrometry (IMS) has been used for over 30 years as a sensitive detector of organic compounds. The following is a brief review of IMS and its principles with an emphasis on its usage when coupled to mass spectrometry. Since its inception, IMS has been interfaced with quadrupole, time-of-flight, and Fourier-transform ion cyclotron resonance mass spectrometry. These hybrid instruments have been employed for the analysis of a variety of target analytes, including biomolecules, explosives, chemical warfare degradation products, and illicit drugs.

Journal Article↗

Effect of fetal calf serum on the cadmium clastogenicity.

Inconsistent results among reports on cadmium genotoxicity revealed that certain confounding factors might significantly influence the outcomes of assessment. In Chinese hamster ovary (CHO-W8) cells, chromosome aberration induced by six different cadmium compounds was found positively associated with intracellular cadmium concentration. A parallel association was also observed among different CHO strains treated with same cadmium compound, the cadmium acetate. Both the cadmium-induced chromosome aberration and cadmium uptake were influenced by the presence of fetal calf serum (FCS). The presence of 10% FCS during the 2h treatment period greatly retarded the cellular cadmium uptake, and concurrently reduced the chromosome aberration induction. Other factors such as specific cadmium anion involved and the duration of cadmium treatment period in the investigation also influenced the assessment results of cadmium-induced chromosome aberration. In the protocol with a 2h pulse treatment, cadmium acetate, chloride and sulfate induced more chromosome aberration than cadmium nitrate, carbonate and oxide. When cadmium was present in the culture of the entire treatment period for 18 h, the results went the opposite way. Cadmium nitrate, carbonate and oxide induced significant chromosome aberration, while other three cadmium compounds gave negative results. Cadmium compounds did not induce significant SCE at the same dose level that yielded significant chromosome aberration induction, either in the protocol with the short pulse or long treatment period.

Animals↗

Role of motility in embryonic development I: Embryo movements and amnion contractions in the chick and the influence of illumination.

This study provides a quantitative analysis of the active movements of the chick embryo and of the contractions of the amnion over the entire developmental period of 21 days. Four types of embryo movements are distinguished. The motor activity of the embryo shows two characteristic peaks, with maximum contraction frequencies on the 12th and on the 16th day. In contrast, the amnion activity is higher at earlier stages and decreases as the body activity increases. The amnion activity is largely independent of the body activity. Illumination has a strong influence on embryo movements. It is shown that increases of light intensity affect the patterns of activity of both the embryo and the amnion. While the effect of light on the embryo can be interpreted as being transmitted via the optic system, the mechanism of the amniotic response is unclear. The results suggest that the amnion itself may be sensitive to light. J. Exp. Zool. (Mol. Dev. Evol.) 291:186-194, 2001.

Amnion↗

Comparison of empirical peak capacities for high-efficiency capillary chromatographic techniques.

Experimental peak capacities for capillary gas chromatography (GC), capillary liquid chromatography (CLC), and capillary electrochromatography (CEC) were compared. To obtain a meaningful comparison, the following constraints were applied. First, the same sample (mixture of alkylbenzenes) was used as a test mixture for all three techniques; second, the same packing material and column diameter were used in CLC and CEC; and third, isothermal conditions were used in GC, while isocratic conditions were used both in CLC and in CEC. Comparison of peak capacities for the same total column efficiency (approximately 36000 plates) showed that the peak capacity of GC is greater than those of the liquid-phase separation techniques. Comparison of CEC and CLC for constant retention factor was also carried out. For this condition, the results depend on the particle size used; for 3-microm porous particles, CEC had a peak capacity larger than CLC due to higher efficiency from the flow profile generated by electroosmotic flow. However, when 1.5-microm nonporous particles were used, the peak capacities were approximately the same for both techniques. The effect of linear velocity on peak capacity was also studied for all three techniques. Practical conditions aimed at increasing peak capacities of liquid-phase separation techniques are discussed.

Journal Article↗

Practical aspects of ultrahigh pressure capillary liquid chromatography.

A novel pressure-balanced injection valve was evaluated for use with ultrahigh pressure liquid chromatography (UHPLC) at pressures up to 120 MPa (1,200 bar). Fused-silica capillaries (30-33 cm x 100 microm I.D.) packed with nonporous 1.5 microm isohexylsilane-modified (C6) silica particles were employed to study maximum pressure, injection reproducibility, injection time, and sample amount consumed for an injection. The new valve was more reproducible, convenient, and required much less sample than previously used injection systems. The effect of column diameter on efficiency and sensitivity was studied. The 100 microm I.D. columns demonstrated approximately 40% lower efficiency but 10-fold higher sensitivity than the 29 microm I.D. columns. Columns packed with nonporous C6 particles produced higher efficiencies than columns packed with a 1.5 microm porous octadecylsilane-modified (C18) material.

Chromatography, High Pressure Liquid↗

Electrospray ionization gas-phase electrophoresis under ambient conditions and it's potential or high-speed separations.

A moderately high resolution nanoelectrospray ionization gas-phase electrophoresis instrument was constructed and evaluated for simple high-speed separations of several groups of compounds. The insertion of a plate containing a 1.6 cm diameter exit orifice, 2.5 cm from the location of electrospray, allowed ions to be created and desolvated under ambient conditions with minimal solvent contamination to the drift tube. Ion separation selectivity is discussed and shown to be slightly altered by changing the drift gas flow rate. Issues of using gas-phase electrophoresis as a high-speed separation technique are discussed. Gas-phase electrophoresis-spectra of selected benzodiazepines, triazine herbicides, and simple combinatorial chemistry libraries are demonstrated.

Alprazolam↗

Bayesian analysis of case control polygenic etiology studies with missing data.

Many genetic studies are based on analysing multiple DNA regions of cases and controls. Usually each is tested separately for association with disease. However, some diseases may require interacting polymorphisms at several regions, and most disease susceptibility is polygenic. In this paper, we develop new methods for determining combinations of polymorphisms that affect the risk of disease. For example, two different genes might produce normal proteins, but these proteins improperly function when they occur together. We consider a Bayesian approach to analyse studies where DNA data from cases and controls have been analysed for polymorphisms at multiple regions and a polygenic etiology is suspected. The method of Gibbs sampling is used to incorporate data from individuals who have not had every region analysed at the DNA sequence or amino acid level. The Gibbs sampling algorithm alternatively generates a sample from the posterior distribution of the sequence of combinations of polymorphisms in cases and controls and then uses this sample to impute the data that are missing. After convergence the algorithm is used to generate a sample from the posterior distribution for the probability of each combination in order to identify groups of polymorphisms that best discriminate cases from controls. We apply the methods to a genetic study of type I diabetes. The protein encoded by the TAP2 gene is important in T cell function, and thus may affect the development of autoimmune diseases such as insulin dependent diabetes mellitus (IDDM). We determine pairs of polymorphisms of genetic fragments in the coding regions of linked HLA genes that may impact the risk of IDDM.

Journal Article↗

Cholinergic activity in autism: abnormalities in the cerebral cortex and basal forebrain.

OBJECTIVE: Measures of cholinergic transmitter activity were investigated in patients with autism because of reported neuropathological abnormalities in cholinergic nuclei in the basal forebrain. METHOD: Levels of cholinergic enzyme and receptor activity were measured in the frontal and parietal cerebral cortex of deceased autistic adults, similarly aged normal adults without mental retardation, and nonautistic mentally retarded adults. The immunoreactivity levels of brain-derived neurotrophic factor and nerve growth factor were measured in the basal forebrain. RESULTS: There were no differences between the autistic and comparison groups in choline acetyltransferase or acetylcholinesterase activity in the cerebral cortex and basal forebrain or in muscarinic M(2) receptor or alpha-bungarotoxin binding within the cortex. Cortical M(1) receptor binding was up to 30% lower than normal in the autistic subjects, and the difference reached significance in the parietal cortex. In both the parietal and frontal cortices, differences in nicotinic receptors assessed by [(3)H]epibatidine binding were significant and extensive (65%-73% lower in the autistic group than in the normal subjects); there were no differences in nicotine binding in the basal forebrain. Immunochemical analysis indicated lower levels of both the alpha(4) and beta(2) nicotinic receptor subunits in the parietal cortex. The M(1) receptor abnormality was not evident in the nonautistic group with mental retardation, although the lower [(3)H]epibatidine binding was apparent. In the basal forebrain, the level of brain-derived neurotrophic factor in the autistic group was three times as high as the level of the normal group. CONCLUSIONS: These neurochemical abnormalities implicate the cholinergic system in developmental disorders such as autism and suggest the potential for intervention based on cholinergic receptor modulation.

Acetylcholinesterase↗