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Biomedical subjects

D A Herold

Publications and source records attributed to D A Herold.

At least 19 recordsLinked to original sources
PubMed2006

Safety of a SQ-standardised grass allergen tablet for sublingual immunotherapy: a randomized, placebo-controlled trial.

BACKGROUND: Sublingual treatment of grass pollen induced rhinoconjunctivitis might provide easier access to specific immunotherapy (SIT) and minimize the risk of serious adverse events (AEs) compared to subcutaneous SIT. AIM OF THE STUDY: To identify a safe dose range for once-daily administration of a grass allergen tablet in participants with grass pollen induced seasonal rhinoconjunctivitis. METHODS: A randomized, double blind, placebo-controlled Phase I trial was conducted outside the grass pollen season. Seven dosage groups [25,000, 75,000, 150,000, 300,000, 500,000, 750,000, or 1,000,000 standardized quality tablet (SQ-T)], consisting of 12 participants randomized either to active treatment or placebo (3 : 1) daily for 28 days, commenced treatment in a staggered manner at intervals of approximately 1 week to allow for intermittent safety reviews. RESULTS: The grass allergen tablet did not cause any serious, systemic or significant (leading to withdrawal) AEs. The overall incidence of AEs was 74% (1,013 events); all of mild or moderate intensity and most considered treatment-related. The most frequently reported treatment-related AEs, including irritation of the throat, and itching sensations in the mouth and ears, increased with dose. These were primarily mild in intensity, started shortly after medication intake and lasted for minutes to a few hours maximum. Objective oral findings were also dose-dependent. No clinically significant observations were found in safety laboratory, vital signs and 12-lead ECG. CONCLUSIONS: A sublingual grass allergen tablet in doses up to 1,000,000 SQ-T daily caused no serious or systemic AEs displaying a safety profile that allows further investigation as once-daily self-medication.

Administration, Sublingual↗
PubMed2003

[Cross-reactive allergen clusters in pollen-associated food allergy].

Immediate symptoms caused by allergens without previous primary sensitization are commonly based on cross-reactive IgE antibodies. They are responsible for pollen-associated food allergies, i.e., fruit allergy in cases of birch pollen allergy or allergy to celery and spices in cases of mugwort pollen allergy. Similar structures between the major allergen of birch pollen (Bet v 1) and a variety of pathogenesis-related proteins from the same family (PR-10), abundant in hazelnuts, fruits, and vegetables, have been well established. Other candidates are profilins, ubiquitous panallergens with little clinical relevance, and stable lipid transfer proteins, responsible for systemic reactions predominantly in Mediterranean countries. Depending on stability, dose, and resorption of these proteins, clinical symptoms are limited to the oro-pharyngeal cavity or develop systemically far from the site of allergen exposure. Clinical diagnosis is based on a positive case history with corresponding allergic sensitization to pollen allergens. Targeted skin testing with native products (i.e., prick to prick test with fresh fruits) appears to be superior for unstable allergens compared to commercial extracts. Individuals should be familiar with cross-reactive patterns; however, allergen avoidance is only recommended in cases of clinical symptoms.

Allergens↗
PubMed1999

Broad spectrum drug identification directly from urine, using liquid chromatography-tandem mass spectrometry.

BACKGROUND: Currently the rate-limiting step for mass spectrometric analysis of drugs in biological samples is sample preparation. Many gas chromatography/mass spectrometry (GC/MS) methods are specific for a certain class of compounds, requiring extraction and/or derivatization before analysis. The purpose of this study was to develop a broad spectrum liquid chromatography/mass spectrometry (LC/MS) procedure that allowed for direct analysis of urine specimens with potential for quantitative analysis. METHODS: We modified a commercially available column-switching instrument, the REMEDi HS from Bio-Rad Diagnostics, to make it compatible with atmospheric pressure ionization. The system we developed was based on electrospray ionization and used three LC columns to extract, purify, and separate drugs directly from urine specimens. Drugs and metabolites were tentatively identified on the basis of retention times and (M+H)(+) ions. Tandem mass spectrometry (MS/MS) was used to confirm the qualitative identification of suspected drugs, using data-dependent acquisition. For quantitative analysis, the cocaine metabolite benzoylecgonine was analyzed using isotope dilution and selected reaction monitoring. RESULTS: Seventeen basic drugs from a variety of classes of compounds were identified directly from urine without the need for prior sample extraction, using LC and MS/MS. Quantitative analysis was demonstrated for benzoylecgonine. When benzoylecgonine-d(3) was used as the internal standard, the method was linear from 30 to 10 000 microgram/L (range tested). At these concentrations, the within-run accuracy was +/- 10% of the target concentration, with CVs <10%. Analytical results by LC/MS/MS compared favorably with GC/MS values for 50 benzoylecgonine-containing specimens and for 25 negative specimens. CONCLUSIONS: The ability to directly analyze urine for a wide variety of drug classes, combined with the sensitivity and specificity of LC/MS/MS makes this technique attractive for many clinical, forensic, and biotechnology applications.

Chromatography, Liquid↗
PubMed1997

Characteristics of a 20-minute whole blood rapid assay for cardiac troponin T.

OBJECTIVES: A qualitative whole blood rapid assay for cardiac troponin T (cTnT) was examined. The assay uses the same antibodies as for a benchmark ELISA, but the capture and detection roles were switched to enhance specificity. DESIGN AND METHODS: The cTnT Rapid Assay and ELISA were compared in 643 samples from patients having myocardial infarction, coronary artery bypass surgery, ischemic heart disease, musculoskeletal disease, renal failure, or other noncardiac conditions. Concordance between the methods was compared using the McNemar Test and cTnT cutoff of 0.2 micrograms/L. RESULTS: For the "cutoff" of 0.2 micrograms/L, concordance between the cTnT Rapid Assay and ELISA was in the range of 90-95% for each group except the renal failure patients, where concordance was 77.9%. There was no significant difference between the cTnT Rapid Assay and ELISA, except in the renal failure and ischemic heart disease patients, where there was a greater number (p < 0.05) of cTnT Rapid Assay negative results when the ELISA was > 0.2 micrograms/L. Overall concordance between the cTnT Rapid Assay and CK-MBmass was 78%. CONCLUSION: The McNemar test indicated that the cutoff for the cTnT Rapid Assay was 0.2 micrograms/L. Evidently the lower concordance among renal failure and ischemic heart disease patients reflects higher cTnT specificity for the Rapid Assay that was conferred by switching the capture and detection antibodies.

Adolescent↗
PubMed1997

Comparison of assay methods for benzodiazepines in urine. A receptor assay, two immunoassays, and gas chromatography-mass spectrometry.

We analyzed 127 urine samples for benzodiazepines by a radioreceptor assay and two immunoassays (cloned enzyme donor immunoassay [CEDIA, Boehringer Mannheim, Indianapolis, Ind] and agglutination immunoassay [ONLINE, Roche Diagnostic Systems, Branchburg, NJ]). Sixty samples that were positive by at least one of these assays were submitted to gas chromatography-mass spectrometry, which detected benzodiazepines such as oxazepam, nordiazepam, and lorazepam in 44 samples. Diagnostic sensitivity and specificity of the receptor assay were almost equal or superior to those of the two immunoassays, although discrepant results were obtained in some samples. The discrepancies resulted from differences in the cross-reactivity of these assays. For example, the receptor assay could detect lorazepam, while the two immunoassays could not, and CEDIA was interfered with by a metabolite of sertraline while the others were not. This is the first report showing the utility of a receptor assay for screening benzodiazepines in urine.

Agglutination Tests↗
PubMed1997

Comparison of an ion-trap and a quadrupole mass spectrometer using diazepam as a model compound.

Recent innovations in mass spectrometry (MS) have led to the development of instruments with increased capabilities, smaller footprints, and relatively low cost. The traditional MS in most toxicology laboratories is a quadrupole system equipped with electron impact ionization. Recently, an ion trap with electron impact, positive chemical ionization, negative chemical ionization, and tandem MS capabilities was introduced by Finnigan MAT. This paper compares the sensitivity and precision of ion-ratio measurements between a Finnigan GCQ ion-trap mass spectrometer (ITMS) and a Hewlett Packard quadrupole mass spectrometer (QMS) using electron impact ionization with diazepam as the model compound. Additionally, the sensitivity and precision of ion ratio measurements are evaluated for the ITMS using positive chemical ionization, negative chemical ionization and tandem MS modes of analysis. In the full scan mode (m/z 50-650, 1 Hz), the ITMS had an average signal-to-noise ratio (S/N) of 1400 for a 2-ng injection of diazepam (10 injections per day for 5 days), within-run ion ratio precision had coefficients of variation from 5 to 11%. Using similar full scan conditions, a 10-ng injection of diazepam on the QMS had an average S/N ratio of 160, and precision of ion ratio measurements varied from 5 to 13%. In the selected ion mode (SIM) of analysis (three ions, 2 Hz), the ITMS had an average S/N of 14,000 for a 2-ng injection and ion-ratio precision ranging from 6 to 15%. Using similar SIM conditions, a 2-ng injection in the QMS had an average S/N of 3000 with ion ratio standard deviations of 0.67 to 2.9%. Overall, the ITMS provided at greater S/N, equivalent precision in full scan, but was 5- to 10-fold less precise in measuring ion ratios in the SIM mode as compared with the QMS.

Anti-Anxiety Agents↗
PubMed1996

Cardiac troponin T is elevated in asymptomatic patients with chronic renal failure.

Patients with chronic renal failure (CRF) are at increased risk for myocardial events that are difficult to evaluate due to atypical symptoms and chronically elevated protein markers of cardiac damage. This study evaluated cardiac troponin T (cTnT), a sensitive marker of cardiac injury, in patients with CRF without myocardial infarction symptoms, and assessed potential causes for elevated cTnT. Blood was obtained from 38 patients with CRF immediately before hemodialysis and from 16 of them post-dialysis, from 21 peritoneal dialysis patients, 10 patients with CRF not on dialysis, 11 patients with cardiomyopathy, and 10 adolescent patients with CRF undergoing hemodialysis. Samples were analyzed for myoglobin, creatine kinase, creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase, lactate dehydrogenase isoenzyme-1 (LD-1), and cTnT. Cardiac TnT was elevated in: 71% of patient with CRF undergoing hemodialysis with no significant differences between pre- and post-dialysis values, 57% of patients with CRF on peritoneal dialysis, 30% of patients with CRF without dialysis, 18% of patients with cardiomyopathy, and 20% of adolescent patients with CRF undergoing hemodialysis. Myoglobin was elevated in almost all patients with CRF undergoing hemodialysis and without dialysis, whereas CK-MB and LD-1 were rarely elevated. Cross-reacting dialyzable substances and myocardial stretch were not major causes for elevated cTnT. Until future studies clarify the etiology of elevated cTnT in patients with CRF, results should be interpreted cautiously.

Adolescent↗
PubMed1996

Comparison of troponin-T with other cardiac markers in a VA hospital.

Measuring protein markers of cardiac damage is important for the diagnosis of myocardial infarction (MI). This study accessed the positive and negative predictive values of cardiac markers for detecting MI and perioperative MI in cardiac surgery by evaluating: creatine kinase (CK); creatine kinase MB isoenzyme mass assay (CK-MB); lactate dehydrogenase (LDH); lactate dehydrogenase isoenzyme-1 (LDH-1); myoglobin; and cardiac troponin T (cTnT) in a Veterans Affairs Medical Center. Inclusion criterion was any patient who had a CK ordered over a 6-month period. Patient history and diagnosis were obtained from discharge summaries. The two groups of patients studied either presented with symptoms of MI (n = 370), or underwent open heart surgery (n = 63). In the patients evaluated for MI, there were 433 suspected cardiac events with 48 MIs diagnosed. Cardiac marker sensitivities and specificities were cTnT (98% and 73%), CK-MB mass (81% and 97%), CK (73% and 78%), LDH (67% and 80%), LDH-1 (33% and 95%), and myoglobin (79% and 66%). For detecting MI, the marker that provided the optimum specificity was CK-MB mass, but cTnT had the highest negative predictive value. There was one perioperative MI in the 63 cardiac surgery patients. Surgical duration and aortic cross clamp time correlated with peak cTnT and CK-MB mass concentrations, but there was a wide degree of variability for any given time period.

Biomarkers↗
PubMed1996

Current techniques in mycobacterial detection and speciation.

Tuberculosis, a health concern so well controlled in recent decades that eradication seemed imminent, is once again reaching epidemic proportions following the increasing prevalence of AIDS. One important means of curbing this resurgence is a robust method that has the capability of identifying and speciating mycobacterial infections in a matter of days. Classic biochemical techniques, which require 4 to 8 weeks to identify and speciate tuberculosis infections, are in the process of being replaced by newer methods, including BACTEC, gene probes, nucleic acid amplification, amplification of ribosomal RNA, high-performance liquid chromatography, and gas chromatography-mass spectrometry. This review is intended to give the reader a synopsis of the current literature and research on these methods, including reliability, approximate time required for detection and speciation, and clinical utility.

Bacteriological Techniques↗
PubMed1996

Determination of blood lead by electron-capture negative chemical ionization gas chromatography-mass spectrometry.

An electron-capture negative chemical ionization (NCI) gas chromatography-mass spectrometry (GC-MS) method for determination of lead (Pb) in blood samples is described. Extraction of Pb from the sample does not involve hot digestion but is based on treatment at ambient temperature. The blood sample is supplemented with a known amount of internal standard (204Pb) for isotope dilution and is treated with concentrated nitric acid. After adjusting the pH to 7, the Pb is extracted into toluene as the pyrrolidine-dithiocarbamate chelate. Samples are then derivatized with 4- fluorophenylmagnesium bromide to form Pb(FC6H4)4. The use of NCI offers enhanced sensitivity (by 75-fold better than previously used electron ionization), gives good precision and accuracy, and has no observable memory effect. The isotope dilution GCoff methodology typically agreed within 2-3% of expected values for the College of American Pathologists blood Pb specimens and the National Institute of Standards and Technology Standard Reference Material 955a.

Gas Chromatography-Mass Spectrometry↗
PubMed1996

Serum total testosterone: immunoassay compared with negative chemical ionization gas chromatography-mass spectrometry.

We have developed an electron capture negative chemical ionization gas chromatography-mass spectrometry (GC-MS) procedure to quantify serum testosterone in the clinically relevant range 0.69-69.3 nmol/L and used this procedure to assess Ciba Corning Diagnostics ACS:180 testosterone immunoassay. The GC-MS method involves liquid-liquid extraction of serum samples and synthesis of a pentafluorobenzyloxime/silyl ether derivative of testosterone with excellent chromatographic and electron capturing properties. The ACS testosterone assay is the first fully automated nonradioactive testosterone immunoassay approved by the US Food and Drug Administration. Patients' specimens (101, 57 males, 44 females) were analyzed by both techniques. A plot of the GC-MS (x) vs ACS (y) testosterone concentrations for men was linear (y = 1.07x + 0.19 nmol/L), showing excellent correlation (r2 = 0.98) between the two assays. Agreement of the two assays for female specimens was poor (y = 0.72x + 1.2 nmol/L), with a poor correlation (r2 = 0.31).

Adult↗
PubMed1996

Hormonal and genetic analysis of a patient with congenital adrenal hyperplasia.

We describe a patient with signs and symptoms of virilization caused by 21-hydroxylase deficiency. The patient, a Hispanic woman, first sought medical attention at age 24, when she presented to a medical clinic with an uncomplicated urinary tract infection. At that time several signs of virilization were noted and she was referred to the endocrinology clinic. Evaluation revealed temporal balding, hyperpigmentation, acne, absent breast development, a muscular habitus, and clitoromegaly. Radiological studies revealed bilaterally enlarged adrenal glands and ovaries. Laboratory evaluation revealed markedly increased concentrations of 17-hydroxyprogesterone, androstenedione, and testosterone. The patient was diagnosed with congenital adrenal hyperplasia (CAH) and received hormone therapy. In her sister, encouraged to undergo testing for this autosomal recessive disorder, HLA testing demonstrated that certain haplotypes in this family were associated with CAH. The case highlights key steps in the laboratory diagnosis and genetics of CAH.

17-alpha-Hydroxyprogesterone↗
PubMed1995

Effects of Vitamin E on susceptibility of low-density lipoprotein and low-density lipoprotein subfractions to oxidation and on protein glycation in NIDDM.

OBJECTIVE: To evaluate the effect of vitamin E supplementation on the susceptibility of low-density lipoprotein (LDL) and LDL subfractions to oxidation and on protein glycation in non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Twenty-one men with NIDDM (HbA1c = 6-10%), ages 50-70, were randomly assigned to either 1,600 IU/day of vitamin E or placebo for 10 weeks after a 4-week placebo period. LDL and LDL subfractions were isolated after 4 weeks of placebo and after 6 and 10 weeks of therapy. Susceptibility of LDL to copper-mediated oxidation was measured by conjugated diene formation (lag time) and formation of thiobarbituric acid-reactive substances (TBARS). Fasting serum glucose, mean weekly blood glucose, HbA1c, and glycated plasma protein concentrations were also determined at these time points. RESULTS: Vitamin E content in plasma and LDL increased 4.0- and 3.7-fold, respectively, in the vitamin E-treated group. Vitamin E decreased the susceptibility of LDL to oxidation in comparison with placebo (lag time, 243 +/- 46 vs. 151 +/- 22 min, P < 0.01; 3 h TBARS, 24 +/- 12 vs. 66 +/- 18 nmol malondialdehyde/mg LDL, P < 0.05). Vitamin E content also increased significantly in both buoyant and dense LDL subfractions, and their oxidation was dramatically reduced. The lag time of LDL oxidation correlated well with the content of vitamin E in both LDL and its subfractions (r = 0.69-0.92). Glycemic indexes did not change significantly in either group during the study. Protein glycation, including glycated hemoglobin, glycated albumin, glycated total plasma proteins, and glycated LDL were unchanged in the vitamin E group. CONCLUSIONS: Supplementation of vitamin E in NIDDM leads to enrichment of LDL and LDL subfractions and reduced susceptibility to oxidation. Despite a greater percentage increase in vitamin E content in small dense LDL, it remained substantially more susceptible to oxidation than was buoyant LDL. This suggests that dense, LDL may gain less protection against oxidation from antioxidant supplementation than does larger, more buoyant LDL. In contrast to previous reports, vitamin E supplementation did not reduce glycation of intracellular or plasma proteins.

Aged↗
PubMed1994

Determination of tellurium in urine by isotope dilution gas chromatography/mass spectrometry using (4-fluorophenyl)magnesium bromide as a derivatizing agent and a comparison with electrothermal atomic absorption spectrometry.

The antitumor drug AS-101 [ammoniumtrichloro (dioxoethylene-O,O')tellurate(IV)] is the first tellurium-containing compound that has been identified as possessing immunomodulating properties and minimal toxicity. We have developed a stable isotope dilution gas chromatography/mass spectrometry method using 120Te as an internal standard and (4-fluorophenyl)magnesium bromide as a derivatizing agent for Te determination in urine. The urine samples were digested using HNO3 + H2O2 prior to derivatization with lithium bis(trifluoroethyl)dithiocarbamate at a pH of 3. The trifluorodiethyldithiocarbamate of tellurium was reacted with the Grignard reagent in anhydrous diethyl ether to obtain Te-(FC6H4)2 for GC/MS analysis. All isotope ratio measurements were made by selected ion monitoring with a Finnigan MAT 8230 organic mass spectrometer using a 10-m fused silica capillary column. Overall percision values for the five major Te isotopes relative to 130Te were 0.6-3.1% when 10-ng samples of chelated Te were analyzed. No appreciable memory or carry-over effect was observed when two synthetic mixtures differing in 120Te:130Te ratios by a factor of 50 were sequentially analyzed. The isotope dilution GC/MS method was validated by determining Te in urine samples and comparing the values with electrothermal atomic absorption spectrometry. Te concentrations were determined in the 100-500 micrograms/L range with CVs of 1-4%.

Gas Chromatography-Mass Spectrometry↗
PubMed1994

Mass spectrometry of trace elements in biological samples.

Mass spectrometry is a powerful analytical tool for determining the isotope ratios and concentrations of trace elements in various samples at levels ranging from major constituents to subparts per billion. Because isotope dilution is free from matrix effects, it has the potential of being incorporated into a definitive analytical approach that can provide reference values for concentrations in physiological and pathological conditions. In addition, isotope dilution mass spectrometry results are free from the constraints of quantitative recovery of the analyte, an essential requirement in other analytical techniques that is difficult to achieve with complex biological samples. A variety of mass spectrometric approaches have been used for determining the concentration of trace elements in biological samples. The more commonly used are thermal ionization mass spectrometry, inductively coupled plasma mass spectrometry, fast atom bombardment mass spectrometry, and gas chromatography mass spectrometry. This article reviews the work on trace element determination in biological samples using different mass spectrometric techniques and highlights the experiments performed by the authors in establishing gas chromatography mass spectrometry.

Animals↗
PubMed1994

Determination of lead in urine and whole blood by stable isotope dilution gas chromatography-mass spectrometry.

A stable isotope dilution gas chromatography-mass spectrometry (GC-MS) method is described for the determination of lead (Pb) in urine and whole blood. The use of lithium bis(trifluoroethyl)dithiocarbamate Pb(FDEDTC) as a chelating agent showed strong memory effect, restricting the range of Pb isotope ratios that can be measured in unknown samples. To overcome this carryover problem, we further derivatized the Pb(FDEDTC)2 chelate with 4-fluorophenyl magnesium bromide to form Pb(FC6H4)4. The sequential analyses of solutions of natural Pb and enriched 204Pb with Pb(FC6H4)4 chelate by GC-MS demonstrated no observable memory effect. Precision and accuracy of Pb isotope ratio measurements with Pb(FC6H4)4 were established, and the isotope dilution GC-MS method was validated by determining Pb concentrations in urine standards from the National Institute of Standards and Technology, urine and blood reference materials from the New York State Department of Health, and blood Pb survey samples from the College of American Pathologists.

Calibration↗