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Biomedical subjects

M L Lee

Publications and source records attributed to M L Lee.

At least 73 records · Page 4Linked to original sources
PubMed1999

Conjugation of 7-oxodehydroabietic acid to lysine, a haptenation mechanism for an oxidized resin acid with dermal sensitizing properties.

This article explores protein conjugation of 7-oxodehydroabietic acid, a resin acid found in both aerosol from soldering with rosin flux and in rosin solids. In a murine model, conjugation (haptenation) of resin acids to proteins is required to generate antibodies against rosin. Hydroperoxy resin acids are dermal sensitizers, with haptenation thought to occur via radical mechanisms. Dermal sensitization to 7-oxodehydroabietic acid has been observed, although no radical haptenation mechanism has been proposed to explain the sensitizing properties of this compound. Conjugation of L-lysine to 7-oxodehydroabietic acid was predicted, with a Schiff base (or imine) linkage formed between C-7 of the resin acid and a free amino group of lysine. Fast atom bombardment mass spectrometry provided evidence of the conjugate; a small peak was seen for the conjugate (M+H)+ ion in aqueous ethanol with 20 mM concentrations of the free resin and amino acids. A larger conjugate peak was observed with addition of tertiary amine as a mild basic catalyst, and the intensity of the conjugate peak exceeded that of the precursors upon replacement of the ethanol with benzene. Resin acids accumulate in the plasma membrane, a non-aqueous environment apparently conducive to conjugation of 7-oxodehydroabietic acid with lysine side chains of membrane proteins. The result would be dehydroabietic acid covalently bound to protein, which could lead to interaction with immune cells having resin acid specificity. The haptenation mechanism presented may be involved in allergic contact dermatitis and occupational asthma observed from exposure to resin acid solids and aerosols. As sampling and analytical methods have been previously demonstrated for 7-oxodehydroabietic acid, this compound may be a useful exposure marker with relevance to negative health effects such as occupational asthma.

Abietanes↗
PubMed1999

Nonlinear models for in vitro kill kinetics of antibiotics.

In this study, we developed nonlinear regression models to analyze the data generated from an in vitro continuous culture system to assess the kinetics of metronidazole and trovafloxacin in inhibiting the growth of Bacteroides fragilis. The model includes parameters describing the initial shock effect of an antibiotic pulse, the overall antibiotic wash-out rate from the system, and the long-term toxicity of the antibiotic in the environment after one pulse and before the next pulse.

Anti-Bacterial Agents↗
PubMed1999

Health habit counseling amidst competing demands: effects of patient health habits and visit characteristics.

OBJECTIVE: This study assesses the effects of competing demands, such as poor health habits or new medical problems, on health-habit counseling during a primary care visit. METHODS: We surveyed a consecutive sample of 1,259 patients visiting primary care clinicians at an academic VA medical center. Before the visit, patients reported their health status, health habits, and sociodemographics; immediately after the visit, patients reported reasons for the visit and whether they had been counseled about specific health habits. We scored visit acuity ranging from visits for unscheduled walk-in care or new medical problems to scheduled visits for check-ups or old problems. We defined counseling "triggers" as clinical indications for counseling about particular health habits (e.g., smoking). We developed a logistic model predicting primary care provider counseling during a visit. RESULTS: Over two-thirds of patients (68.9%) received some health habit counseling. Controlling for other independent variables, patients with more triggers were more likely to report being counseled. Counseling rates went up as visit acuity went down; patients with the lowest visit acuity having 67% greater odds of being counseled than patients with the highest visit acuity. CONCLUSIONS: Physicians set priorities for health-habit counseling during a visit based on patients' health habit problems or triggers; whether the visit is scheduled or walk-in; and whether the patient has new or acute problems. Future research about primary care performance of health habit counseling should account for these patient and visit characteristics, and prevention-oriented health care organizations should ensure access to scheduled "check-up" visits.

Aged↗
PubMed1999

Validation of patient reports, automated pharmacy records, and pill counts with electronic monitoring of adherence to antihypertensive therapy.

OBJECTIVES: To evaluate the validity of patient report, pharmacy dispensing records, and pill counts as measures of antihypertensive adherence using electronic monitoring as the validation standard. METHODS: The study was conducted among 286 members of Harvard Pilgrim Health Care, a managed care organization, who were at least 18 years of age, on monotherapy for hypertension, and had prescription drug coverage. Prescription refill adherence during the 12 months before enrollment was determined from their automated pharmacy dispensing records. Participants were interviewed about their medication adherence before and after a 3-month electronic monitoring period during which pill counts were also performed. Adherence to both recommended number and timing of doses was estimated from electronic monitoring data. Data analysis was based on statistical correlation and analysis of variance. RESULTS: Electronic adherence monitoring revealed that the proportion of prescribed doses consumed was higher (0.92) than the proportion of doses taken on time (0.63). The correlation between adherence to quantity and timing of doses was 0.32. Concurrent pill counts and earlier refilling patterns were moderately correlated with electronic monitoring (pill count: r = .52 with quantity and r = .17 with timing; refill adherence r = .32 with quantity and r = .22 with timing). There was considerable misclassification of adherence reported by patients, although nonadherence was generally accurately reported. CONCLUSIONS: Deviation from recommended timing of doses appears to be greater than from prescribed number of doses. Pharmacy dispensing records demonstrate predictive validity as measures of cumulative exposure and gaps in medication supply. Adherence levels determined from pill counts and pharmacy dispensing records correlate more closely with quantity than with timing of doses. Nonadherence reported by patients can serve as a qualitative indicator and predictor of reduced adherence.

Adolescent↗
PubMed1999

Resource utilization associated with initial hospital stays complicated by early onset group B streptococcal disease.

BACKGROUND: The epidemiology of early onset neonatal group B streptococcal (GBS) disease has changed appreciably, but there are no recent assessments of the in-hospital resource utilization it incurs. STUDY DESIGN: We performed a retrospective cohort study of infants delivered from 1987 through 1995 at Massachusetts' largest obstetrics hospital. A matched cohort design was used to assess care occurring after transfer to another acute care hospital. RESULTS: There were 135 cases of early onset neonatal GBS infection complicating 85,062 deliveries (1.6/1,000 births) in 9 years, with a substantial decline beginning in 1994, when maternal intrapartum chemoprophylaxis was widely introduced. Most (73%) infants had birth weights of 2500 g or more; 93% survived. Overall both the median and mean lengths of stay were 8 days longer for infants with GBS disease than for those without this infection (P < 0.001). Total hospital charges for neonates with GBS disease also were higher, with the difference in medians of $5323 and in means of $10,004 (P < 0.001). Differences were greatest among >2500-g birth weight infants; no excess was evident for infants with birth weights of < 1500 g. CONCLUSION: There was a substantial excess length of stay and charges associated with early onset neonatal GBS disease, although this was less than previously reported.

Cost of Illness↗
PubMed1999

Statistical inference for serial dilution assay data.

Serial dilution assays are widely employed for estimating substance concentrations and minimum inhibitory concentrations. The Poisson-Bernoulli model for such assays is appropriate for count data but not for continuous measurements that are encountered in applications involving substance concentrations. This paper presents practical inference methods based on a log-normal model and illustrates these methods using a case application involving bacterial toxins.

Algorithms↗
PubMed1999

The independent contribution of bone and erythrocyte lead to urinary lead among middle-aged and elderly men: the normative aging study.

Plasma is the component of blood from which lead is free to cross cell membranes and cause organ toxicity. Plasma lead levels, however, are extremely low and difficult to measure. Urinary lead originates from plasma lead that has been filtered at the glomerular level; thus, urinary lead adjusted for glomerular filtration rate serves as a proxy for plasma lead levels. In this investigation we examined the interrelationships of lead levels in whole blood corrected by hematocrit [i.e., erythrocyte lead (EPb)], trabecular bone (TBoPb), cortical bone (CBoPb), and urine excreted over 24 hr (UPb); all samples were obtained from 71 middle-aged and elderly men with no known occupational lead exposures. Lead was measured by graphite furnace atomic absorption spectroscopy (blood), K-X-ray fluorescence (bone), and inductively coupled plasma mass spectroscopy (urine). Lead levels were generally low, with mean EPb, TBoPb, and CBoPb values of 13.8, 31.1, and 21.7 microg/g, respectively, and a median UPb value of 6.15 microg/day. In generalized additive models adjusted for body weight and creatinine clearance rate, both EPb and bone lead variables remained independently and significantly associated with UPb. This finding suggests that bone influences plasma lead in a manner that is independent of the influence of erythrocytic lead on plasma lead. Thus, the superiority of bone lead over blood lead in predicting some chronic forms of toxicity may be mediated through bone's influence on plasma lead. In addition, this study suggests that measurement of urinary lead might be useful as a proxy for plasma lead levels in studies of lead toxicity.

Aged↗
PubMed1999

Chemical detection in deployment toxicology using high speed gas chromatography with a solvating mobile phase and time-of-flight mass spectrometry.

Solvating gas chromatography (SGC) involves a mobile phase that is a supercritical fluid at the column inlet (typically 100-350 atm) and a gas upon exiting the column at ambient pressure. SGC has characteristics of both supercritical fluid chromatography and gas chromatography, and may be adaptable to a system with characteristics approaching a "universal chromatograph" capable of analyzing many classes of compounds on one instrument. We have recently found that using a solvating mobile phase such as CO2, together with small, spherical particle-packed capillary columns can offer significant advantages for rapid chemical analysis. A need exists in operational military settings to rapidly detect a wide range of chemicals with potential adverse health effects for exposed personnel. A separation step improves analytical capability by reducing or eliminating chemical background for better detection limits, and purifies or isolates target analytes and unknowns for improved identification. SGC, coupled to a high volume vapor/aerosol sampler and a rapid mass spectrometric detector such as a time-of-flight mass spectrometer could provide rapid, positive identification of separated compounds, with the resulting chromatographic and mass spectral data stored in digital format for future retrieval. Such a system will significantly advance the ability of military commanders to detect airborne chemical agents rapidly and accurately, protecting the health of military personnel.

Chemical Warfare Agents↗
PubMed1999

Idiotypic vaccination with a murine anti-dsDNA antibody: phase I study in patients with nonactive systemic lupus erythematosus with nephritis.

OBJECTIVE: To determine the safety and immunogenicity of an idiotypic anti-dsDNA vaccine in patients with nonactive systemic lupus erythematosus (SLE) and stable lupus nephritis. METHODS: Patients with SLE with a history of nephritis were randomized for vaccination with the murine anti-dsDNA monoclonal antibody (Mab) 3E10 in a dose ranging, double blind, placebo controlled study (phase I). RESULTS: Of the 9 patients injected with Mab 3E10, 5 showed a human anti-mouse antibody (HAMA) response, in large part antiidiotypic, which developed within the first 3 months in 3 strong HAMA responders, and more than one year after immunization in an initially weak HAMA responder. All but one nonresponder were receiving low dose prednisone. No adverse events, in particular no evidence of lupus flares, and no untoward laboratory findings were reported over a followup of 2 years. CONCLUSION: In patients with stable lupus nephritis, immunization with Mab 3E10 appears safe and can generate a significant antiidiotypic response. Idiotypic vaccination may be an approach to specific immunotherapy of autoimmune lupus nephritis.

Adult↗
PubMed1998

Transarterial approach of the pulmonary artery in anatomically corrected malposition of the great arteries by manipulating a catheter inverted with balloon floating maneuver.

We describe two neonates with anatomically corrected malposition of the great arteries (ACM). A 1-day-old female newborn, who had the salient clinical findings of Goldenhar syndrome, behaved like a patient with the tetralogy of Fallot. The cardiac malformations included ACM, perimembranous inlet and outlet ventricular septal defect with tricuspid valve straddling, conoventricular septal malaligement, bilateral cori without aortic-mitral continuity, pulmonary stenosis at subvalvular, valvular, and supravalvular levels, and bicuspid semilunar valves. After the procedure of left Blalock-Taussig shunt at 3 months of age, cyanosis was alleviated. The other 1-month-old male newborn, who presented with prolonged feeding, tachypnea and tachycardia, likened to a patient with the hypoplastic left heart syndrome. He had a combination of ACM, mitral stenosis, hypoplastic left atrium and left ventricle, a restrictive patent foramen ovale, ventricular septal defect, subaortic conus without aortic-mitral continuity, subaortic stenosis, and a narrow ascending aortic root. Rashkind balloon atrioseptostomy was done with limited success. He survived a Norwood procedure. Transarterial entry of the catheter, which was inverted with the aid of balloon floating maneuver, to hook the retro-aortic pulmonary artery in ACM is recommended.

Angiography↗
PubMed1998

Clinical implications of isolated double aortic arch and its complex with intracardiac anomalies.

From July 1, 1989 to June 30, 1996, a total of six patients, four male and two female, with double aortic arch (DAA) were registered. They aged 16 days to 6.5 years. There were two patients with isolated DAA, and four complicated with intracardiac anomalies. All six patients presented respiratory distress and feeding problem early in life. However, cyanosis, owing to decreased pulmonary blood flow, predominated the clinical picture in each patient having DAA intricated with tetralogy of Fallot (TOF) and pulmonary stenosis, TOF with absent pulmonary valve syndrome, and type II-A tricuspid atresia. DiGeorge syndrome was documented in one patient with TOF and pulmonary stenosis. Expiratory wheezing was remarkable in the patient with TOF and absent pulmonary valve syndrome. Mild cyanosis and heart failure was noted in one patient with ventricular septal defect (VSD), and bicuspid pulmonary valve with mild valvular stenosis. Barium esophagogram showed indentations on esophagus in five patients. Echocardiography was yielding in three infants. Four patients, two isolated and two complex DAA, survived the surgical division of the smaller left aortic arch. One-stage and two-stage operation was performed in patients having DAA intricated with VSD and TOF, respectively. The other two patients with complex DAA remained in close observation owing to the tolerance of symptoms related to intracardiac anomalies.

Aorta, Thoracic↗
PubMed1998

Isothermal and nonisothermal decomposition of thymopentin and its analogs in aqueous solution.

PURPOSE: The degradation kinetics of thymopentin (RKDVY) and its analogs (RKDVW and RPDVY) in aqueous solution was studied by isothermal and nonisothermal methods. METHODS: The isothermal decomposition of thymopentin and its analogs was investigated as a function of pH (2-10), temperature (37, 57, and 80 degrees C) and ionic strength (micro = 0.02 to 1). Nonisothermal decomposition studies were performed using a linear temperature programmer. The temperature increasing rate was set to 0.25 degrees C per hour and the temperature interval varied from 40 to 88 degrees C. RESULTS: The decomposition of thymopentin and its analogs followed first order kinetics. The dependence of the rate constant on temperature followed a linear Arrhenius plot. This indicated that the degradation mechanism of thymopentin and its analogs might be the same within the temperature range studied. The energies of activation were found to be in close agreement for the isothermal and nonisothermal studies, suggesting that the nonisothermal studies may save considerable amount of time in the early stages of drug development. The logK-pH profile of thymopentin suggests that maximum stability is achieved in the pH range of 6-8. CONCLUSIONS: These results indicate that the nonisothermal methodology provides an attractive alternative to isothermal methods, as it requires a much lower amount of both material and time, to determine the peptide stability and to estimate the shelf-life for peptide pharmaceutical preparations.

Drug Stability↗
PubMed1998

Capillary electrophoresis--time-of-flight mass spectrometry of drugs of abuse.

The use of capillary electrophoresis (CE) for the determination of drugs of abuse was explored. A commercial CE system was interfaced with a laboratory-built time-of-flight mass spectrometer (TOFMS) which was equipped with a high-speed data acquisition system to provide accurate monitoring of efficient separations. Ionization of the CE eluent was achieved with an electrospray ionization source. Standard mixtures and seized samples were analyzed either by direct infusion of the analyte solutions or after separation by CE. Detection at the low femtomole level was obtained using CE-TOFMS.

Amphetamine↗
PubMed1998

Analyzing the time and value of housestaff inpatient work.

OBJECTIVE: To determine time allocation and the perceived value to education and patient care of the weekday activities of internal medicine housestaff on inpatient rotations and to compare the work activities of interns and residents. DESIGN: An observational study. We classified activities along five dimensions (association, location, activity, time, and value), developed a computer-assisted self-interview survey, and demonstrated its face and content validity, internal consistency, and interrater reliability. Subjects were assigned survey computers for 5 consecutive weekdays over a 24-week period, into which they entered data when prompted several times a day. SETTING: The medical service of a university-affiliated Veterans Administration Medical Center. PARTICIPANTS: Sixty housestaff (36 interns, 24 residents) rotating on the inpatient wards. MEASUREMENTS AND MAIN RESULTS: We analyzed activities according to content (direct patient care, indirect patient care, education), association, and location. Likert-scale ratings of perceived value to education and patient care were also obtained. Housestaff provided complete responses to 3,812 (95%) of 3,992 prompts by a median of 11 seconds; 93% of responses were logically consistent across the measured dimensions. Housestaff spent more time in indirect patient care (56%) than in direct patient care (14%) or educational activities (45%). Formal educational activities had the highest educational value (66 on 0-100 scale), and direct care had the highest value to patient care (81). Over 30% of time was spent in administrative activities, which had low educational value(40). Compared with residents, interns allocated significantly less time to educational activities (38% vs 57%) and more time to lower-value activities such as documentation (19% vs 12%). CONCLUSIONS: Improved data collection methods demonstrate that housestaff in our program, particularly interns, spend much of their workday in activities that are low in educational and patient care value. Selective elimination or delegation of such activities would preserve higher-value experiences during reductions in overall inpatient training time. Planners can use automated random sampling to guide the rational redesign of housestaff work.

Confidence Intervals↗
PubMed1998

Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis.

We wanted to assess whether intravenous immunoglobulin G (IVIG) decreases disease activity on MRI in relapsing MS. Previous trials of IVIG in relapsing-remitting MS demonstrated a reduction of acute relapses, but these studies did not include MRI. We treated 26 patients in a randomized, double-blind, crossover study of IVIG 1 g/kg daily or placebo on 2 consecutive days every month during two 6-month treatment periods. The primary end point was the number of gadolinium-enhancing lesions on monthly serial MRI. Secondary efficacy variables were the occurrence of exacerbations, clinical neurologic ratings, total MS lesion load on T2-weighted MRI, and multimodal evoked potentials. Eighteen patients completed the entire trial; eight patients did not. Twenty-one patients completed the first treatment period and at least two MRI examinations in the second treatment period and were included in the intention-to-treat analysis. On serial MRI, we observed fewer enhancing lesions per patient per scan during IVIG treatment (median, 0.4; range, 0 to 9.3) than during placebo treatment (median, 1.3; range, 0.2 to 25.7; p = 0.03). During IVIG treatment, 15 patients were exacerbation free compared with only 7 on placebo (p = 0.02). The total number of exacerbations in the IVIG period was 11 and in the placebo period, 19 (not significant). None of the remaining secondary efficacy measures were significantly different between the two treatment periods. The number of adverse events, in particular eczema, was significantly higher during IVIG therapy than during placebo treatment. These results suggest that IVIG treatment is beneficial to patients with relapsing MS.

Adolescent↗
PubMed1998

MR imaging of pelvic floor continence mechanisms in the supine and sitting positions.

OBJECTIVE: Our goal was to determine the anatomic differences in pelvic floor anatomy for continent women and women with stress incontinence using MR imaging and to assess whether these anatomic differences depend on the position of the subject during imaging. SUBJECTS AND METHODS: Eight continent volunteers and eight women with stress incontinence underwent MR imaging in the supine and sitting positions. For imaging, we used an open-configuration 0.5-T magnet. T2-weighted images were obtained in the midline sagittal plane with subjects at rest and at maximal pelvic floor strain in 5 sec using a modified fast spin-echo sequence. In the axial plane, thin-section T2-weighted images were obtained with subjects at rest using a standard fast spin-echo technique. Images were evaluated for mobility of the urethra and bladder neck and for integrity of the vagina, levator ani, and supporting fascia. RESULTS: Pelvic floor laxity and abnormalities of the supporting fascia were more common in incontinent women than in continent women. Both descent of the bladder neck when subjects strained and the posterior urethrovesical angle were not significantly greater when subjects were measured in the sitting position (p < .1). CONCLUSION: Changes of pelvic floor laxity related to incontinence can be seen with subjects in both the supine and the sitting positions but are increased in the sitting position.

Adult↗