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Biomedical subjects

T Law

Publications and source records attributed to T Law.

At least 19 recordsLinked to original sources
PubMed2005

Lead in paint and soil in Karnataka and Gujarat, India.

Blood lead surveys in several areas of India have found very high percentages of children with elevated blood lead levels. Fifty-three percent of children under 12 years of age in a seven-city screening had blood lead levels equal to or greater than 10 microg/dL, the level currently considered elevated by the U.S. Centers for Disease Control and Prevention (CDC). A number of these surveys focused on populations near lead smelters or in areas with high lead levels from combustion of lead-containing gasoline. There is little information available, however, on the levels of lead in paint in India and in soil. Field portable X-ray fluorescence analyzers were used to determine environmental lead levels in paint, dust, air, soil, and other bulk samples near several lead-using industries and in the residential environments of children with very high blood lead levels, at least four times as high as the CDC limit. Soils near industrial operations, such as secondary lead smelters, and battery dismantling units contained levels up to 100,000 ppm of lead. Four of 29 currently available paints from five manufacturers measured 1.0 mg/cm2 or above--the current U.S. definition of lead-based paint in housing-after the application of a single coat; four others measured at least 1.0 after three coats, and three others likely reached this level after the application of an additional one or two coats. In 5 of 10 homes of the elevated blood lead children, three or more locations in or around the home were found to have lead paint levels of 1.0 mg/cm2 or higher. Soil exceeding the U.S. standard for residential areas (400 ppm) was found at only one of the houses. Other sources of lead exposure, including traditional ayurvedic medicine tablets, were also observed. Similar surveys would be useful elsewhere in India and in other developing countries.

Data Collection↗
PubMed2005

Tandem mass spectrometry method for the quantification of serum busulfan.

Busulfan, an alkylating agent, is most commonly used as a component of bone marrow transplantation preoperative regimens. Significant interpatient and intrapatient variations in pharmacokinetics require individualizing the dosage based on area under the time-versus-concentration curve. Timely result reporting is critical to dose adjustment to reduce morbidity and mortality associated with the regimen. The authors developed a rapid, accurate, and sensitive method for the quantification of serum busulfan using direct inject tandem mass spectrometry. Plasma samples (50 microL) are extracted in 1 mL of methanol containing 1,6-bis-(methanesulfonyloxy)hexane as an internal standard. The supernatant is dried under nitrogen (40 degrees C, 30 minutes) and then dissolved in 200 microL methanol and transferred into a clean glass vial suitable for LC/MS/MS analysis. The sample is delivered using an HPLC pump that delivers 0.2 mL of methanol per minute, and 20 microL of sample is injected into a turbo ion spray-equipped tandem mass spectrometer. Total analysis time is 5 minutes. The Q1/Q3 transition for busulfan (BU) is monitored at 269/55 and 297.1/55.1 for the internal standard. The assay is linear to 10 micromol/L and sensitive to at least 0.5 micromol/L. The interassay reproducibility at 1, 2.2, and 4.4 micromol/L were 4.2%, 5.6%, and 6.3%, respectively. Within-run precision using 3 different control samples was 3.9%, 3.9%, and 6.9%. Mean recovery of 4 different BU concentrations spiked into 10 different BU free plasma samples was 98%. Correlation with an established HPLC-UV method revealed a slope of 0.98, an intercept of 0.1, and r = 0.95 (n = 48). No significant interfering substances or ion suppression was identified. This method is a significant improvement over the existing HPLC-UV method for BU determination. The method is highly accurate, reproducible, and requires less specimen, sample preparation, and analysis time.

Antineoplastic Agents, Alkylating↗
PubMed2003

Medical needs of people with intellectual disability require regular reassessment, and the provision of client- and carer-held reports.

BACKGROUND: Previous work has indicated a wide range of unmet medical health needs in people with intellectual disability (ID). METHODS: A profile of recorded medical needs was produced for 589 people with ID through a detailed search of individual medical and nursing case records. Specialist optometric and audiological assessments were offered, and reports were provided in technical and plain English terms. A Health Watch project delivered folders with copies of the plain English reports to 60 individuals and carers. RESULTS: The case record review indicated a wide range of medical disorders; however, exact diagnoses and counselling regarding underlying neurological conditions were seldom recorded. Assessed levels of hearing and vision loss were much greater than had been previously recognized. The Health Watch reports were welcomed by the clients and carers. CONCLUSIONS: If satisfactory healthcare is to be achieved for people with ID, medical needs must be monitored, regular specialist reassessments offered, access to specialist services facilitated and reports clearly explained to carers.

Adolescent↗
PubMed2000

Home phototherapy for neonatal jaundice--technology and teamwork meeting consumer and service need.

32 babies with uncomplicated physiological jaundice received home phototherapy from a hospital/community team in southern Brisbane. All babies showed acceptable reductions in their serum bilirubin on home therapy, and none required hospital re-admission for phototherapy. Their families were highly satisfied with the home program, and recorded high levels of confidence in their therapeutic responsibilities. Community providers were able to deliver a high quality 24-hour service, integrated with appropriate neonatology support. The cost of delivering the home program was significantly less than a comparable hospital stay.

Bilirubin↗
PubMed2000

Agreement among four homocysteine assays and results in patients with coronary atherosclerosis and controls.

BACKGROUND: Hyperhomocysteinemia has been associated with coronary atherosclerosis in many, but not all, prospective and retrospective studies. Some on these inconsistencies may be attributed to methodological variabilities. METHODS: In the present study, three newly commercially available assays and one in-house HPLC assay for total homocysteine (tHcy) were utilized in 99 subjects with angiographically documented atherosclerosis and in 91 community controls matched by age, gender, and smoking history. The in-house assay, a modified Fortin and Genest HPLC method, was compared with the Bio-Rad HPLC assay, the Abbott IMx((R)) fluorescence polarization immunoassay, and a Bio-Rad enzyme-linked immunoassay (EIA) microtiter method. RESULTS: Correlation coefficient values between the in-house HPLC assay and the Bio-Rad HPLC, the Abbott IMx, and the Bio-Rad EIA assays were 0.95, 0.96 and 0.90, respectively. Although tHcy concentrations were higher in cases compared with controls by all four methods, the difference reached statistical significance only with the in-house HPLC procedure (median, 13.5 +/- 6.7 micromol/L in cases vs 10.9 +/- 4.8 micromol/L in controls; P <0. 01, adjusting for covariates), where it was an independent predictor of case or control status, along with hypertension, total cholesterol, and triglycerides. The tHcy distributions in cases and controls demonstrated significant overlap. The number of atherosclerotic major coronary vessels was associated with significantly higher tHcy (P <0.01 for trend) in all four methods. CONCLUSIONS: The three commercial assays for tHcy differed in analytical and clinical performance. Analytically, the Abbott IMx method showed the best comparability with the in-house assay, but clinically, the three commercial methods were similar and did not distinguish cases from controls.

Arteriosclerosis↗
PubMed1999

Elevated serum vascular endothelial growth factor in children and young adults with Crohn's disease.

Vascular endothelial growth factor (VEGF) is a cytokine released by fibroblasts, epithelial cells, and leukocytes that potentiates vascular permeability and growth of new capillaries. Because of these multiple effects, VEGF has been postulated to play a role in the pathogenesis of autoimmune disease, as well as in wound healing. We hypothesized that VEGF was potentially important in mediating the vascular permeability and angiogenesis seen in Crohn's disease, and therefore that VEGF would be increased in the serum of children with Crohn's disease. Serum was obtained from 73 children and young adults with Crohn's disease, 47 with ulcerative colitis, and 29 controls. VEGF levels were measured by enzyme-linked immunosorbent assay. Mean VEGF levels were significantly higher in patients with Crohn's disease (436.4 +/- 37.2 pg/ml) than in ulcerative colitis (306 +/- 41.1 pg/ml) or control (167.8 +/- 29.6 pg/ml) patients. Serum VEGF also correlated significantly with disease activity, being elevated in patients with moderate/severe Crohn's disease and ulcerative colitis. We conclude that serum VEGF is released by inflamed tissues in children with Crohn's disease. This multifunctional cytokine could promote inflammation by increasing vascular permeability or promote wound healing by mediating capillary growth.

Adolescent↗
PubMed1998

Vitamins A and E serum levels in children and young adults with inflammatory bowel disease: effect of disease activity.

BACKGROUND: Hypovitaminosis and fat-soluble vitamin deficiency have been reported in adults with inflammatory bowel disease (IBD). A prospective study was undertaken to determine the prevalence of low serum levels of vitamins A and E in children and young adults with IBD. METHODS: Clinical information and serum for vitamin levels was gathered prospectively from 61 patients with Crohn's disease, 36 patients with ulcerative colitis, and 23 control subjects. Disease activity and disease location were determined for IBD patients. Serum retinol and alpha-tocopherol levels were determined by high-performance liquid chromatography. RESULTS: The prevalence of hypovitaminosis A (defined as serum vitamin A < 20 micrograms/dl) or hypovitaminosis E (defined as serum vitamin E < 5 mg/l) was 16% in the pediatric IBD population studied. Low vitamin A levels were more common than low vitamin E levels. Serum retinol levels correlated significantly with alpha-tocopherol levels. Hypovitaminosis was significantly more prevalent in the Crohn's disease patients who had active disease, an erythrocyte sedimentation rate of more than 25 mm/hour, or a serum albumin level less than 3 mg/dl. CONCLUSIONS: Children and young adults with active IBD frequently have low serum levels of vitamin A or vitamin E. The severity of disease activity is a better predictor of risk for hypovitaminosis than is nutritional status. Further work is necessary to determine whether the hypovitaminosis seen in children with IBD reflects true deficiency.

Adolescent↗
PubMed1998

Analytical and clinical performance of a homogeneous enzymatic LDL-cholesterol assay compared with the ultracentrifugation-dextran sulfate-Mg2+ method.

LDL-cholesterol (LDL-C) concentration is currently determined in most clinical laboratories by the Friedewald calculation. This approach has several limitations and may not meet the current total error requirement in LDL-C measurement of < or = 12%. We evaluated the analytical and clinical performance of the direct N-geneous LDL-C assay (Equal Diagnostics). The N-geneous method correlated highly with the modified beta-quantification assay (r = 0.95; y = 0.91x + 70.6 mg/L; n = 199), showed no significant effect of increased triglyceride or other common interferants, and performed adequately in serum samples from nonfasting individuals. This assay demonstrated a mean total error of 6.75% over a wide range of LDL-C concentrations. In addition, at the medical decision cutoff points, this LDL-C assay showed positive predictive values of 78-95% and negative predictive values of 84-99%. We conclude that the N-geneous LDL-C meets the currently established analytical performance goals and appears to have a role in the diagnosis and management of hypercholesterolemic patients.

Cholesterol, LDL↗
PubMed1998

Assessment of interlaboratory performance in external proficiency testing programs with a direct HDL-cholesterol assay.

Direct assays for the determination of HDL-cholesterol (HDL-C) have recently become available. The methods are precise, require small sample volume, and appear to be less affected by increased triglycerides than traditional precipitation methods. In this study, we describe the inter- and intralaboratory variability of the Boehringer Mannheim Corporation direct HDL-C assay and its performance in external proficiency testing surveys. A comparison study among three laboratories, using different analyzers and 85 serum specimens, showed a correlation coefficient (r) of 0.99. The direct HDL-C assay also showed good agreement with the ultracentrifugation-dextran sulfate-Mg2+ method (r = 0.98) and the Cholesterol Reference Method Laboratory Network-Designated Comparison Method (a = 0.98x + 4.75 mg/L, r = 0.98). Total error at medical decision levels ranged from -0.8% to +11.1%. Furthermore, this assay performed adequately in the College of American Pathologists and the ALERT surveys as well as the CDC Lipid Standardization Program and met all performance criteria of regulatory agencies.

Centers for Disease Control and Prevention, U.S.↗
PubMed1997

Serum basic fibroblast growth factor in pediatric Crohn's disease. Implications for wound healing.

Basic fibroblast growth factor is a heparin-binding protein known to stimulate angiogenesis and promote wound healing in tissues. Since Crohn's disease is characterized in part by submucosal vascular proliferation, we sought to determine whether serum basic fibroblast growth factor is elevated in children with Crohn's disease and whether serum levels reflect disease activity. Sera were obtained from 64 children with Crohn's disease, 44 children with ulcerative colitis, 20 children with functional abdominal pain, and 29 from children with documented inflammatory disease evaluated in our gastroenterology program. Disease activity indices and clinical data were gathered prospectively for the inflammatory bowel disease patients. Serum basic fibroblast growth factor levels were measured by enzyme-linked immunosorbent assay. Although the mean basic fibroblast growth factor level did not significantly differ between children with Crohn's disease and other conditions, there was a strong (r = 0.53, P < 0.001) correlation between basic fibroblast growth factor level and disease activity. The relationship of basic fibroblast growth factor with disease activity persisted even after adjusting for other covariates (including age, sex, hematocrit, albumin, and sedimentation rate) in a multivariate linear regression model. There was also a statistically significant, although less strong correlation (r = 0.33, P = 0.03) between basic fibroblast growth factor level and disease activity in ulcerative colitis. While basic fibroblast growth factor is not a specific marker for Crohn's disease, serum levels reflect disease activity. Therefore, basic fibroblast growth factor release may be important in mediating the angiogenesis and wound healing seen in Crohn's disease.

Adolescent↗
PubMed1997

Measurement of plasma ketoprofen by a rapid high-performance liquid chromatography assay.

The authors developed a high performance liquid chromatography assay for the determination of plasma ketoprofen concentration using a single-step extraction, a short chromatographic separation of 3 min, and a sample volume of 50 microliters. The assay possessed linearity up to 500 mg/l, sensitivity down to at least 1 mg/l, average recovery of 100.1%, and run-to-run precision (n = 20) of 4.6% at a level of 10 mg/l and 2.2% at a level of 40 mg/l. Furthermore, the assay was free of interference from 51 prescription and over-the-counter medications. The authors conclude that the method described here is ideally suited for the determination of ketoprofen concentration in a clinical laboratory setting for the purpose of therapeutic monitoring and assessment of toxicity.

Chromatography, High Pressure Liquid↗
PubMed1997

Three generations of high-density lipoprotein cholesterol assays compared with ultracentrifugation/dextran sulfate-Mg2+ method.

We report on the analytical performance of three generations of HDL-cholesterol assays: phosphotungstic acid/Mg2+, Spinpro, and a homogeneous method, N-geneous. The run-to-run imprecision (CV) of all assays was < or = 4.9%, and all results correlated highly with those of a modified reference procedure (r > or = 0.96). At triglycerides concentrations < 4000 mg/L, these field methods showed an acceptable systematic error (y = 1.12x - 47, 1.05x - 23, and 0.96x + 8 for the phosphotungstate, Spinpro, and N-geneous assays, respectively), and the total error of the field methods met the current National Cholesterol Education Program (NCEP) performance goal of < or = 22%. Regression analyses of results for samples with triglycerides > 4000 mg/L produced the following results for the above respective assays: y = 1.08x - 4.2, 1.02x + 3.6, and 0.85x + 108. In this hypertriglyceridemic group, only the N-geneous assay (at an HDL-cholesterol content of 240 mg/L) had a total error (35%) that exceeded the NCEP limit. Bilirubin and ascorbate produced a negative interference with the phosphotungstate and Spinpro assays but had little effect on the N-geneous assay.

Ascorbic Acid↗
PubMed1996

Elevation of serum interleukin-6 but not serum-soluble interleukin-2 receptor in children with Crohn's disease.

Previous studies have demonstrated elevated serum levels of interleukin-6 (IL-6) and the soluble interleukin-2 receptor (IL-2R, CD25) in individuals with inflammatory bowel disease (IBD). The aim of our study was to compare serum IL-6 and IL-2R levels to see if one marker better distinguished IBD from other intestinal disorders or better reflected disease activity. Blood samples were obtained from 41 pediatric patients with Crohn's disease, 22 with ulcerative colitis, 19 with other gastrointestinal inflammatory disorders, and 13 with functional abdominal pain. Disease activity and disease location were determined for patients with Crohn's disease and ulcerative colitis. Serum levels of IL-6 and IL-2R were determined by using an enzyme-linked immunosorbent assay. Mean serum levels of IL-6 were significantly elevated (p < 0.05) in patients with Crohn's disease when compared with individuals with ulcerative colitis, other gastrointestinal inflammatory disorders, or functional abdominal pain. By comparison, there was no significant difference in mean serum levels of IL-2R in individuals with Crohn's disease compared with these other groups. Patients with moderate/severe Crohn's disease had elevated mean serum levels of IL-6 and IL-2R when compared with those with mild and inactive disease (p < 0.05); however, neither marker distinguished between inactive and mild disease. IL-6 correlated better with the erythrocyte sedimentation rate (ESR; r = 0.57, p < 0.001) than did IL-2R (r = 0.28, p < 0.01). Our results suggest that elevated IL-6 levels a.e more likely to be seen in patients with Crohn's disease. Although IL-6 may be a better marker for Crohn's disease and active disease than IL-2R, it does not appear to offer any advantage over the ESR.

Adolescent↗
PubMed1996

Delta F508-CFTR channels: kinetics, activation by forskolin, and potentiation by xanthines.

Trafficking, activation, and kinetics of delta F508-cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR were compared in stably transduced C127I mouse mammary epithelial cells. Western blots detected a small amount of fully glycosylated delta F508-CFTR Efflux of 125I was stimulated by forskolin with the same mean effective concentration (EC50; approximately 0.5 microM) for CFTR and delta F508-CFTR cells, but the maximum response was reduced more than fivefold and its latency increased approximately threefold in delta F508-CFTR cells. In delta F508-CFTR cells, 3-isobutyl-1-methylxanthine (IBMX; EC50 = 1.45 microM) and 8-cyclopentyl-1,3-dipropylxanthine (CPX; EC50 = 58 microM) increased the peak forskolin-stimulated efflux rate approximately 2.5-fold and decreased the time to peak. A sevenfold increase in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels accompanied potentiation of forskolin-induced 125I efflux by IBMX but not by CPX. Elevation of intracellular cAMP increased linear voltage-independent whole cell currents 30-fold in CFTR and 4-fold in delta F508-CFTR cells; the response rate in delta F508-CFTR cells was much slower. Single-channel currents were detected in 57 of 68 cell-attached patches from forskolin-prestimulated CFTR cells vs. 6 of 35 patches in delta F508-CFTR cells. Mean number of active channels per patch was 4.1 for CFTR [open probability (Po) = 0.34] and 0.2 for delta F508-CFTR (Po = 0.11). The lower Po of delta F508-CFTR resulted from an approximately threefold longer mean interburst interval. We estimate that forskolin-stimulated chloride conductance of delta F508-CFTR C127I cells is < 5% of CFTR cells. CPX is approximately 25-fold more potent than IBMX in potentiating delta F508-CFTR and may operate by a mechanism other than elevation of cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Comparison of the fast-start performances of closely related, morphologically distinct threespine sticklebacks (Gasterosteus spp.)

Fast-start escape performances for two species of threespine stickleback, Gasterosteus spp., were investigated using high-speed cinematography (400 Hz). The two fishes (not yet formally described, referred to here as benthic and limnetic) inhabit different niches within Paxton Lake, British Columbia, Canada, and are recent, morphologically distinct species. All escape responses observed for both species were double-bend C-type fast-starts. There were no significant differences between the species for any linear or angular parameter (pooled averages, both species: duration 0.048 s, distance 0.033 m, maximum velocity 1.10 m s-1, maximum acceleration 137 m s-2, maximum horizontal angular velocity 473.6 rad s-1 and maximum overall angular velocity 511.1 rad s-1). Benthics and limnetics have the greatest added mass (Ma) at 0.3 and 0.6 body lengths, respectively. The maximum Ma does not include the fins for benthics, but for limnetics the dorsal and anal fins contribute greatly to the maximum Ma. The deep, posteriorly placed fins of limnetics enable them to have a fast-start performance equivalent to that of the deeper-bodied benthics. Both the limnetic and benthic fishes have significantly higher escape fast-start velocities than their ancestral form, the anadromous threespine stickleback Gasterosteus aculeatus, suggesting that the high performance of the Paxton Lake sticklebacks is an evolutionarily derived trait. In this biomechanical study of functional morphology, we demonstrate that similar high fast-start performance can be achieved by different suites of morphological characteristics and suggest that predation might be the selective force for the high escape performance in these two fishes.

Journal Article↗
PubMed1996

Use of a rapid HPLC assay for determination of pharmacokinetic parameters of ibuprofen in patients with cystic fibrosis.

High doses of ibuprofen have been shown to delay the progression of lung disease without serious adverse effects in patients with cystic fibrosis. To be effective, peak ibuprofen concentration of 50 to 100 mg/L has to be achieved. We developed an HPLC assay to rapidly determine plasma ibuprofen concentration. We used this assay to determine the pharmacokinetics of ibuprofen in patients with cystic fibrosis. The assay possessed linearity up to 500 mg/L, sensitivity to 1 mg/L, average recovery of 98%, and run-to-run precision (n = 23) of 3%. Furthermore, the assay proved to be free of interference from 51 medications. Observed time to peak concentration varied significantly between those receiving ibuprofen tablets (mean + SD, 94 +/- 29 min, n = 16) and syrup (30 +/- 0 min, n = 4) (P < 0.0001). We conclude that the method described here is ideal for therapeutic monitoring of ibuprofen.

Adolescent↗
PubMed1995

Genetic questions for environmental studies. Differential parenting and psychopathology in adolescence.

BACKGROUND: Recent genetic evidence suggests that the most important environmental influences on normal and pathologic development are those that are not shared by siblings in the same family. We sought to determine the relationship between differences in parenting styles and depressive symptoms and antisocial behavior in adolescence, and to compare the influence of these nonshared experiences with genetic influences. METHODS: We studied 708 families with at least two same-sexed adolescent siblings who were monozygotic twins (93 families), dizygotic twins (99 families), ordinary siblings (95 families), full siblings in step families (181 families), half siblings in step families (110 families), and genetically unrelated siblings in step families (130 families). Data on parenting style were collected by questionnaire and by video recording of interaction between parents and children. RESULTS: Almost 60% of variance in adolescent antisocial behavior and 37% of variance in depressive symptoms could be accounted for by conflictual and negative parental behavior directed specifically at the adolescent. In contrast, when a parent directed harsh, aggressive, explosive, and inconsistent parenting toward the sibling, we found less psychopathologic outcome in the adolescent. CONCLUSIONS: Parenting behavior directed specifically at each child in the family is a major correlate of symptoms in adolescents. Furthermore, harsh parental behavior directed at a sibling may have protective effects for adolescents, a phenomenon we call the "siblin barricade."

Adolescent↗