Biomedical subjects

M L Lee

Publications and source records attributed to M L Lee.

At least 37 records · Page 2Linked to original sources

PubMed2001

Effects of gonadal steroid suppression on skeletal sensitivity to parathyroid hormone in men.

Hypogonadism is associated with osteoporosis in men. GnRH- agonist-induced hypogonadism increases bone turnover and bone loss in men, but the mechanism underlying these changes is unknown. To determine whether gonadal steroid deprivation increases the skeletal sensitivity to PTH or blunts the ability of PTH to promote 1,25-dihydroxyvitamin D formation, we infused human PTH-(1-34) at a dose of 0.55 U/kg.h for 24 h, in 11 men (ages, 50-82 yr) with locally advanced, node-positive, or biochemically recurrent prostate cancer but no evidence of bone metastases. PTH infusions were performed before initiation of GnRH agonist therapy (leuprolide acetate, 22.5 mg im, every 3 months) and again after 6 months of confirmed GnRH agonist-induced hypogonadism. Serum osteocalcin (OC), bone- specific alkaline phosphatase (BSAP), N-telopeptide (NTX), whole-blood ionized calcium, and 1,25-dihydroxyvitamin D were measured at baseline and every 6 h during each PTH infusion. Urinary NTX and free deoxypyridinoline (DPD) were assessed on spot morning samples before PTH infusion and on 24-h samples collected during the PTH infusions. Sex steroid levels were lowered to the castrate range in all subjects. Baseline serum NTX levels (drawn before PTH infusion) increased from 9.1 +/- 3.7 before leuprolide therapy to 13.9 +/- 5.0 nmol bone collagen equivalents (BCE)/L after leuprolide therapy (P = 0.003). Spot urine NTX collected before PTH infusion increased from 28 +/- 8 before leuprolide therapy to 49 +/- 17 nmol BCE/mmol creatinine after leuprolide therapy (P < 0.001), and urinary DPD increased from 4.7 +/- 1.1 to 7.4 +/- 1.8 nmol BCE/mmol creatinine (P < 0.001). Baseline serum OC and BSAP levels drawn before each PTH infusion did not change before vs. after leuprolide therapy. Serum NTX levels increased significantly during PTH infusion pre-GnRH agonist therapy (P < 0.001), and the rate of increase was greater after 6 months of GnRH agonist-induced hypogonadism (P < 0.01 for the difference in rates of change before and after GnRH agonist administration). Serum OC and BSAP levels decreased during PTH infusion (P < 0.001 for OC and P = 0.002 for BSAP), but the rates of decrease did not differ before or after leuprolide therapy (P = 0.45 for OC and P: = 0.19 for BSAP). Whole-blood ionized calcium levels increased during PTH infusion (P < 0.001), and the rate of increase was greater after GnRH agonist-induced hypogonadism (P = 0.068). Serum 1,25-dihydroxyvitamin D levels increased in response to PTH infusion before leuprolide therapy (P = 0.022), but there was no difference in the rate of increase before or after leuprolide therapy (P = 0.66). The incremental increase in urinary NTX excretion, but not DPD, during PTH infusion was greater after 6 months of leuprolide therapy (P = 0.029 for NTX, P = 0.578 for DPD). We conclude that suppression of sex steroids in elderly men increases the skeletal responsiveness to the bone resorbing effects of PTH infusion but does not affect the response of bone formation markers or 1,25-dihydroxyvitamin D to PTH. Changes in skeletal sensitivity to PTH may play an important role in the pathogenesis of hypogonadal bone loss in men.

Aged↗

PubMed2001

Influence of bone resorption on the mobilization of lead from bone among middle-aged and elderly men: the Normative Aging Study.

Bone stores of lead accrued from environmental exposures and found in most of the general population have recently been linked to the development of hypertension, cognitive decrements, and adverse reproductive outcomes. The skeleton is the major endogenous source of lead in circulating blood, particularly under conditions of accelerated bone turnover and mineral loss, such as during pregnancy and in postmenopausal osteoporosis. We studied the influence of bone resorption rate on the release of lead from bone in 333 men, predominantly white, middle-aged and elderly (mostly retired) from the Boston area. We evaluated bone resorption by measuring cross-linked N-telopeptides of type I collagen (NTx) in 24-hr urine samples with an enzyme-linked immunosorbent assay. We used K-X-ray fluorescence to measure lead content in cortical (tibia) and trabecular (patella) bone; we used graphite furnace atomic absorption spectroscopy and inductively coupled plasma mass spectroscopy to measure lead in blood and urine, respectively. After adjustment for age and creatinine clearance, the positive relation of patella lead to urinary lead was stronger among subjects in the upper two NTx tertiles (beta for patella lead > or =0.015) than in the lowest NTx tertile (beta for patella lead = 0.008; overall p-value for interactions = 0.06). In contrast, we found no statistically significant influence of NTx tertile on the relationship of blood lead to urinary lead. As expected, the magnitude of the relationship of bone lead to urinary lead diminished after adjustment for blood lead. Nevertheless, the pattern of the relationships of bone lead to urinary lead across NTx tertiles remained unchanged. Furthermore, after adjustment for age, the relation of patella lead to blood lead was significantly stronger in the upper two NTx tertiles (beta for patella lead > or =0.125) than in the lowest NTx tertile (beta for patella lead = 0.072). The results provide evidence that bone resorption influences the release of bone lead stores (particularly patella lead) into the circulation.

Adult↗

PubMed2001

Combined atrial and arterial switch operations for congenitally corrected transposition.

Conventional repair of congenitally corrected transposition of the great arteries (CCTGA) is directed at eliminating the associated defects and leaves the right ventricle in a systemic position. The long-term outcome of this procedure may involve deterioration of right ventricular function with tricuspid regurgitation and failure of the conduction system. We describe two consecutive patients with CCTGA, one of whom had apicocaval juxtaposition. The patients were aged 19 and 16 months, respectively, and both underwent a combination of atrial and arterial switch. These are the first two reported cases of successful completion of this type of operation in Taiwan. Our review of previously reported cases suggested that no significant difference exists in the outcome of patients with this condition who undergo either arterial switch or Rastelli-type repair plus atrial redirection. However, reported patients who underwent anatomic repair had lower early mortality, late mortality, and incidence of complete heart block than those who underwent conventional repair. The present two cases and our review of the literature suggest that, among patients with apicocaval juxtaposition, 1) Mustard operation is optimal for patients with small atrial volume; 2) one-and-one-half ventricular repair may be helpful to the outcome, especially when treatment is combined with Rastelli-type repair; and 3) excellent access to the ventricular septal defect through the tricuspid valve is afforded via a left atriotomy. From the present two cases and our review of the literature, we conclude that anatomic repair is superior to conventional repair of CCTGA in terms of protection against dysfunction and failure of the anatomic right ventricle, tricuspid valve, and conduction system. Long-term follow-up is mandatory.

Cardiac Surgical Procedures↗

PubMed2001

Modified arterial switch operation by sharing the common wall between the great arteries.

BACKGROUND: Suprapulmonary stenosis and coronary arterial obstruction still remain as problems after an arterial switch operation (ASO). We used a modified ASO applying the common wall and in situ transfer techniques to improve the current procedure. METHODS: From October 1996 to December 1997, 11 babies aged 6 days to 3 months with transposition of the great arteries underwent a modified ASO which included sharing the common wall between the great arteries until above the anterior neoaortic suture-line for coronary and pulmonary artery reconstruction. Coronary arteries were of usual type in three cases, juxtacommissural origin in five, and a high takeoff in one; all were redirected almost in situ. RESULTS: There was no early death (< 30 d), coronary or bleeding problems. One late death occurred after a repeat surgery for suprapulmonary stenosis. This was caused by upward stretching of the left pulmonary artery, which was placed above the high left-sided neoaortic anastomosis for in situ transfer of the high takeoff coronary arteries. Intraluminal growth of the adventitia also contributed to suprapulmonary stenosis, which decreased significantly when the common wall adventitia was cleaned in the last two cases we operated on. Ten patients were doing well at follow-up (30.9 +/- 5.2 mo). CONCLUSIONS: This modified ASO by common wall and in situ transfer might avoid coronary kinking and lessen the chance of postoperative bleeding. To avoid suprapulmonary stenosis, common wall adventitia inside the pulmonary pathway should be cleaned, and the left and right pulmonary arteries should also be kept in situ as possible as in coronary redirection.

Humans↗

PubMed2001

Echocardiographic assessment of total anomalous pulmonary venous connections in pediatric patients.

BACKGROUND AND PURPOSE: Cardiac catheterization can be superfluous and risky for sick babies, infants, and young children with total anomalous pulmonary venous connection (TAPVC). This study assessed the accuracy of echocardiography in the clinical assessment of pediatric patients with TAPVC before cardiac surgery. PATIENTS AND METHODS: A total of 15 consecutive patients with TAPVC treated between July 1, 1993, and December 31, 1999, were included in this retrospective study. Patients with TAPVC with heterotaxy syndrome were excluded. We assessed this cardiac anomaly preoperatively using plain chest roentgenograms, echocardiography, and magnetic resonance imaging. A combination of suprasternal, parasternal, subcostal, and apical four-chamber views and their tilting scans were employed for diagnosis and to trace the course of the anomalous pulmonary venous connection. RESULTS: Interatrial right-to-left shunt via atrial septal defects were documented by two-dimensional echocardiography with color Doppler mapping in all 15 patients. Patent ductus arteriosus was found in six patients. Cardiomegaly with enlargement of the right atrium and the right ventricle could be seen on plain chest roentgenograms and by echocardiography in all but two patients with infracardiac TAPVC. In all patients, the left innominate vein, coronary sinus or right atrium, and portal vein were the draining sites of supracardiac, cardiac, and infracardiac TAPVC, respectively. A pattern of continuous flow without phasic variation, which is suggestive of stenosis of the pulmonary vein, was found in two patients with infracardiac TAPVC with obstruction. The surgical findings were reviewed and correlated well with those of the echocardiography. CONCLUSIONS: In infants and children with TAPVC, the drainage sites and flow profiles of the pulmonary veins can be exactly determined by Doppler echocardiography preoperatively, which makes cardiac catheterization and angiocardiography unnecessary.

Child↗

PubMed2000

Solvating gas chromatography with chemiluminescence detection of nitroglycerine and other explosives.

A separation technique known as solvating gas chromatography (SGC), which utilizes packed capillary columns and neat carbon dioxide as mobile phase, was used for the separation of nitroglycerine (NG) and other nitrogen-containing explosives including 2,6-dinitrotoluene (2,6-DNT), 2,4-dinitrotolulene (2,4-DNT), 2,4,6-trinitrotoluene (2,4,6-TNT), and pentaerythritol tetranitrate (PETN). SGC was coupled for the first time to a selective chemiluminescence thermal energy analyzer (TEA) detector for nitro-functional group specificity and sensitive detection of these compounds. TEA calibration curve for NG showed linearity in the sub-microg ml(-1) range. Soil samples containing NG were used to test the validity of the technique. Detector response of SGC-TEA versus SGC-flame ionization detection for NG was also evaluated.

Chromatography, Gas↗

PubMed2000

Fast gas chromatography: packed column solvating gas chromatography versus open tubular column gas chromatography.

Packed capillary column solvating gas chromatography (SGC) and open tubular column gas chromatography (GC) were compared with respect to their potentials for fast separations. A recently introduced "universal" peak capacity equation was used to compare the performance of these two methods. The effects of various factors on peak capacity were investigated. Results demonstrate that retention factor and column efficiency are the main factors affecting peak capacity for fast separations. Packed columns produce both high retention factors and high selectivities. While high efficiencies and high peak capacities can be demonstrated by both techniques, open tubular column GC can surpass packed capillary column SGC in both measurements, except for the case of the analysis of simple mixtures in short analysis times, where retention factor and selectivity become important. Practical aspects such as pressure drop and sample capacity are compared for SGC and open tubular column GC. It was found that packed column SGC demonstrates higher sample capacities, but requires much higher column inlet pressures than open tubular column GC. A variety of mobile phases can be used for packed column SGC, which can provide high solvating power for large and polar compounds.

Chromatography, Gas↗

PubMed2000

Importance of replication in microarray gene expression studies: statistical methods and evidence from repetitive cDNA hybridizations.

We present statistical methods for analyzing replicated cDNA microarray expression data and report the results of a controlled experiment. The study was conducted to investigate inherent variability in gene expression data and the extent to which replication in an experiment produces more consistent and reliable findings. We introduce a statistical model to describe the probability that mRNA is contained in the target sample tissue, converted to probe, and ultimately detected on the slide. We also introduce a method to analyze the combined data from all replicates. Of the 288 genes considered in this controlled experiment, 32 would be expected to produce strong hybridization signals because of the known presence of repetitive sequences within them. Results based on individual replicates, however, show that there are 55, 36, and 58 highly expressed genes in replicates 1, 2, and 3, respectively. On the other hand, an analysis by using the combined data from all 3 replicates reveals that only 2 of the 288 genes are incorrectly classified as expressed. Our experiment shows that any single microarray output is subject to substantial variability. By pooling data from replicates, we can provide a more reliable analysis of gene expression data. Therefore, we conclude that designing experiments with replications will greatly reduce misclassification rates. We recommend that at least three replicates be used in designing experiments by using cDNA microarrays, particularly when gene expression data from single specimens are being analyzed.

DNA, Complementary↗

PubMed2000

Capillary electrochromatography using continuous-bed columns of sol-gel bonded silica particles with mixed-mode octadecyl and propylsulfonic acid functional groups.

Continuous-bed columns containing sol-gel bonded 3 microm silica particles with mixed-mode octadecyl and propylsulfonic acid functional groups (ODS/SCX) were prepared by first packing the ODS/SCX particles into a fused-silica capillary, then filling the packed capillary with a siliceous sol-gel, curing the sol-gel, and finally drying the column with supercritical carbon dioxide. The performance of the sol-gel bonded ODS/SCX columns was evaluated for capillary electrochromatography using acetonitrile aqueous mobile phase containing phosphate buffer. The columns were mechanically strong and permeable. Both EOF velocity and current increased linearly with elevation of the applied electric field strength. The EOF velocity was high at low pH and nearly constant over a range of pH 2-9. Higher buffer concentration resulted in higher current and lower EOF velocity. The acetonitrile content had no significant effect on the EOF. Without thermosetting the column, no bubble formation was noticed with currents up to 2.5 microA. The minimum plate height of a 25/34 cm x 75 microm I.D. sol-gel bonded 3 microm ODS/SCX column was 5.7 microm (1.75 x 10(5) plates per meter) at an optimum EOF velocity of 0.92 mm s(-1). Mixtures of test aromatic compounds and aromatic hydrocarbon homologues gave symmetrical peaks when using a low pH mobile phase. The retention and elution order of aromatic compounds represented a typical reversed-phase separation mechanism similar to conventional ODS columns. The run-to-run and column-to-column retention factor reproducibility was better than 2.5% and 8.0% RSD, respectively.

Acetonitriles↗

PubMed2000

Reversed-phase liquid chromatography of proteins and peptides using multimodal copolymer-encapsulated silica.

Multimodal copolymer-encapsulated particles for liquid chromatography were prepared by bonding 1-octadecene and unsaturated carboxylic acids on silica particles (5 microm diameter, 300 A pores) for liquid chromatography of proteins. These multimodal copolymer-encapsulated particles can provide both hydrophobic and hydrogen bonding interactions with polar compounds. The chromatographic performance of these multimodal copolymer-encapsulated particles for peptide and protein separations was evaluated under reversed-phase conditions. Compared with typical C8-bonded silica, polymer-encapsulated particles were more stable in acidic mobile phases and provided better recoveries, especially for large proteins (Mr>0.5 x 10(6)). Totally hydrophobic polymer-encapsulated particles were found to produce broad peaks for proteins, and significant improvements were observed by introducing hydrophilic groups (-COOH) onto the polymer-encapsulated surface to form a multimodal phase. For the reversed-phase liquid chromatography of peptides and proteins, improved selectivity and increased solute retention were found using the multimodal polymer-encapsulated particles. More peaks were resolved for the separation of complex peptide mixtures such as protein digests using the multimodal polymer-encapsulated particles as compared to totally hydrophobic polymer-encapsulated particles.

Chromatography, High Pressure Liquid↗

PubMed2000

A pharmacodynamic assessment of the impact of antihypertensive non-adherence on blood pressure control.

OBJECTIVES: To evaluate if antihypertensive regimens that conform to present FDA guidelines by maintaining > or = 50% of their peak effect at the end of the dosing interval protect patients during sporadic lapses in adherence. METHODS: 169 patients on monotherapy for high blood pressure underwent electronic adherence monitoring for 3 months. Blood pressures were measured during non-study office visits and were retrieved from automated medical records. Questionnaires were used to obtain other covariate information. The ratio of the dosing interval to the half-life of drug activity (I') was used to capture conformity with FDA guidelines. Data analysis focused on the interaction between I' and the impact on blood pressure of delayed dosing. RESULTS: The average (+/- standard deviation) blood pressure during the study was 139.0(+/- 12.0)/85.0(+/- 6.9) mm Hg. Lisinopril followed by sustained-release verapamil, atenolol, and hydrochlorothiazide were the most frequently prescribed agents. The majority of regimens (99%) conformed to FDA dosing guidelines. Of the patients 23% missed a dose before their blood pressure check. Non-adherence, however, did not have a direct impact on blood pressure, and no interaction with I' of was detected. CONCLUSIONS: Among patients with relatively mild hypertension on single-drug therapy, regimens that conform to current FDA dosing guidelines may prevent losses of blood pressure control during episodic lapses of adherence. These findings should be replicated in other patient populations with standardized blood pressure measurement to confirm their validity.

Adult↗

PubMed2000

Modified arterial switch operation by spiral reconstruction of the great arteries in transposition.

BACKGROUND: Spiral relationship of the normally related great arteries (SRGA) has never been reconstructed in an arterial switch operation. METHODS: From March 1998 to April 1999, 9 consecutive cases of transposition of the great arteries (TGA) family (from 2 days to 1.6 years old) underwent arterial switch operations with SRGA at our hospital. Two had a congenitally corrected TGA (plus atrial redirection). Lecompte maneuver was not used in all. The posterior wall of pulmonary trunk was not divided but three were reattached, two of whom had had previous pulmonary trunk banding. Thus the wall was shared between the great arteries facing each other. RESULTS: All survived the operation. Supraaortic stenosis was balloon-dilated in 2 cases of early series, but technical modifications later were able to avoid it. Angiogram showed smooth flow into SRGA without upward and anterior tilting of the pulmonary bifurcation. All great and coronary arteries were patent. All were doing well on follow-up (16.5 +/- 4.2 months). CONCLUSIONS: We concluded that the techniques to relocate the coronary arteries using common wall and in situ switch could also be applied to pulmonary arterial reconstruction, so that SRGA can be resumed in TGA.

Anastomosis, Surgical↗

PubMed2000

Comparison of immediate and deferred colposcopy in a cervical screening program.

OBJECTIVE: To evaluate the effect of delaying colposcopy in women with negative Papanicolaou smears and positive speculoscopy results. METHODS: This was a prospective study of asymptomatic women ages 13-60 years, regularly scheduled for pelvic examinations. All women had Papanicolaou smears and magnified visual examinations with speculoscopy. Women with negative Papanicolaou smears and positive speculoscopy results were quasirandomized to immediate or deferred colposcopy groups. RESULTS: A total of 800 women completed all phases of the study, 124 of whom had negative Papanicolaou smears and positive speculoscopy results. Among 57 women who had immediate colposcopies, 64.9% had histologic evidence of neoplasia. Sixty-seven women had their scheduled colposcopies deferred for 6 months. During this period, 21% (14) were lost to follow-up and 29% (13) of those evaluated converted from speculoscopy positive to speculoscopy negative. Among the 32 (71%) women who remained speculoscopy positive, 90% were found to have histologic evidence of neoplasia on colposcopic biopsy. CONCLUSION: In women with normal Papanicolaou smears and positive speculoscopy results, the diagnostic yield can be improved by deferring colposcopy for 6 months. Deferral should be considered only for women who are reliable for follow-up.

Adolescent↗

PubMed2000

De novo design of molecular architectures by evolutionary assembly of drug-derived building blocks.

An evolutionary algorithm was developed for fragment-based de novo design of molecules (TOPAS, TOPology-Assigning System). This stochastic method aims at generating a novel molecular structure mimicking a template structure. A set of approximately 25,000 fragment structures serves as the building block supply, which were obtained by a straightforward fragmentation procedure applied to 36,000 known drugs. Eleven reaction schemes were implemented for both fragmentation and building block assembly. This combination of drug-derived building blocks and a restricted set of reaction schemes proved to be a key for the automatic development of novel, synthetically tractable structures. In a cyclic optimization process, molecular architectures were generated from a parent structure by virtual synthesis, and the best structure of a generation was selected as the parent for the subsequent TOPAS cycle. Similarity measures were used to define 'fitness', based on 2D-structural similarity or topological pharmacophore distance between the template molecule and the variants. The concept of varying library 'diversity' during a design process was consequently implemented by using adaptive variant distributions. The efficiency of the design algorithm was demonstrated for the de novo construction of potential thrombin inhibitors mimicking peptide and non-peptide template structures.

Algorithms↗

PubMed2000

Pulmonary venous obstruction in patients with transposition of the great arteries.

We report two cases of complete transposition of the great arteries with pulmonary venous obstruction which was diagnosed by intraoperative transesophageal echocardiography, but was not detected by transthoracic echocardiography and cardiac catheterization. The pulmonary venous obstruction was relieved simultaneously with arterial switch operation. The intraoperative transesophageal echocardiography has great contribution for thorough evaluation of the pulmonary venous return of the patients.

Echocardiography↗

PubMed2000

Rapid separation of nitroaromatic compounds by solvating gas chromatography.

Nitroaromatic compounds such as 2,4,6-trinitrotoluene are used in the production of explosive and munitions, and are environmental contaminants as a result of such use. Conventional methods to detect these compounds have relied on liquid and gas chromatography to isolate the individual compounds which may be present at low levels in complex environmental matrices before final detection and identification. A new method, solvating gas chromatography, was used to rapidly separate 8 nitroaromatic compounds, showing improved speed relative to conventional liquid and gas chromatography methods. Solvating gas chromatography allows near real-time detection for these energetic compounds, providing improvements in their detection as environmental contaminants, and as compounds of interest to law enforcement and military organizations.

Chromatography, Gas↗

PubMed2000

Invasive disease due to group B Streptococcus in pregnant women and neonates from diverse population groups.

From 1993 through 1996, surveillance for invasive disease due to group B Streptococcus (GBS) in neonates aged <7 days and in peripartum pregnant women was performed in a racially and ethnically diverse cohort in 4 cities in the United States. In a birth population of 157,184, 130 neonatal cases (0.8 per 1000) and 54 maternal cases (0.3 per 1000) were identified. Significant correlates with neonatal disease were black or Hispanic race and a birth weight <2500 g. The attack rate for peripartum maternal infection varied widely by city and may have been influenced by the frequency of administration of intrapartum antibiotics or of evaluating febrile women by performance of blood cultures. Pregnancy loss or GBS disease in the infant occurred in 28% of these maternal cases. Among neonatal and maternal GBS isolates, serotypes Ia (34%-37%) and III (25%-26%) predominated, and type V was frequent (14%-23%). These results provide a description of invasive GBS perinatal infection during the period in which guidelines for prevention were actively disseminated.

Age Distribution↗

PubMed2000

Successful transcatheter coil embolization of coronary artery fistula in an infant.

Congenital coronary artery fistula is a rare anomaly that can cause several types of morbidity as well as mortality. Recently, transcatheter coil embolization for congenital coronary artery fistula has been advocated as an effective alternative to surgical repair and is associated with a low morbidity and good clinical outcome. We report a 49-day-old infant who had tachycardia, tachypnea, prolonged and interrupted feeding, cardiomegaly, and continuous murmur, and who underwent successful transcatheter coil embolization for a congenital right coronary artery fistula. At review 1 year after coil occlusion showed that serial plain chest radiographs, myocardial enzyme analysis, electrocardiography, and wall motion on echocardiography were normal.

Aortography↗