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Biomedical subjects

R L Bertholf

Publications and source records attributed to R L Bertholf.

At least 19 recordsLinked to original sources
PubMed2001

Protecting human research subjects.

Respect for persons, beneficence, and justice are the cardinal principles that guide the ethical conduct of research on humans. Past abuses of human research subjects prompted medical organizations and governmental agencies to develop guidelines that ensure the protection of human research subjects. Human research funded by the U.S. government is strictly regulated, and Institutional Review Board approval of the experimental protocol is required prior to the award. Under limited circumstances, human research may be exempted from review, or review may be expedited. Research involving specimens submitted for pathological examination or diagnostic studies sometimes qualifies for these special categories of limited review. Academic pathologists and laboratorians should be aware of the regulations that apply to research on human subjects.

Bioethics↗
PubMed2001

Detection of cocaine and its metabolites in breast milk.

A method was developed for measuring cocaine and its metabolites, benzoylecgonine, ecgonine methyl ester, norcocaine, ecgonine ethyl ester, cocaethylene, and m-hydroxybenzoylecgonine, in breast milk by gas chromatography/mass spectrometry. Limits of detection for this method ranged from 2.5 to 10 ng/mL, and limits of quantitation ranged from 5 to 50 ng/mL. For each of the compounds measured by this method, linear response was demonstrated to 750 ng/mL. Breast milk was collected from 11 mothers who admitted to drug use during pregnancy and ten drug-free volunteers serving as control subjects. Cocaine was detected in six of the specimens obtained from drug-exposed subjects, and in none of the drug-free control subjects. In breast milk specimens where cocaine and one or more of its metabolites were detected, the concentration of parent compound was greater than any of the metabolites. The highest cocaine concentration found was over 12 microg/mL. Breast-fed infants of cocaine abusing mothers may be exposed to significant amounts of drug orally.

Adult↗
PubMed2000

Modification of screening immunoassays to detect sub-threshold concentrations of cocaine, cannabinoids, and opiates in urine: use for detecting maternal and neonatal drug exposures.

Testing for drugs of abuse in urine is commonplace in emergency departments and neonatal units. However, the clinical sensitivity of immunochemical screening methods is limited by the threshold concentrations used to distinguish between positive and negative specimens. Immunochemical screening methods for cocaine metabolite (benzoylecgonine), cannabinoids, and opiates in urine were recalibrated to detect drugs at lower threshold concentrations. The precision and linearity of the signals at the modified thresholds were verified by diluting drug-positive urine specimens to concentrations below the conventional cutoff concentration and measuring the rate signals in triplicate. To assess the clinical performance of the modified methods, specimens that tested negative using the unmodified assays were re-screened at the lower threshold, and specimens that re-screened positive were submitted for gas chromatographic/mass spectrometric (GC/MS) confirmation. Reproducibility of sub-threshold measurements was comparable to the unmodified assays, and rate separations between successive dilutions were sufficient to give semi-quantitative results. Using the lower thresholds, drugs were detected in 4-5% of the subjects that had screened negative at the conventional threshold concentration. GC/MS analysis confirmed the presence of cannabinoids and cocaine metabolite in 74% and 84%, respectively, of urine specimens that re-screened positive. Morphine, codeine, hydromorphone, or hydrocodone was detected by GC/MS analysis in 31% of opiate-positive re-screens.

Adult↗
PubMed2000

Discordant results of CK-MB and troponin I measurements: a review of 14 cases.

In the course of a clinical comparison involving 204 parallel total creatine kinase (CK), creatine kinase-MB isoenzyme (CK-MB), and cardiac troponin I (cTnI) measurements, 12 patients were identified in whom cTnI was elevated while total CK was normal, as well as 2 patients in whom CK-MB was elevated while cTnI was normal. CK-MB relative index was elevated in 6 of the twelve cTnI-positive patients with normal total CK; only 2 of these patients had a discharge diagnosis of acute myocardial infarction (AMI). All of the 12 patients in this group had medical conditions that are associated with greater risk for acute cardiac events. Both patients with normal cTnI but elevated total CK and CK-MB index had chronic renal insufficiency; one of these patients had a positive stress test and a diagnosis of AMI. The other cTnI-negative patient died 2 days after admission, and autopsy revealed evidence of ischemic changes, but not acute infarction. Significant differences were apparent between traditional CK-MB results and cTnI measurements. Using total CK elevation as a prerequisite for subsequent CK-MB measurement may limit the clinical sensitivity of this enzyme marker for detecting subacute ischemic damage to the myocardium. Elevated total CK and CK-MB isoenzyme without corresponding elevations in cTnI, on the other hand, may reflect changes in enzyme elimination kinetics due to renal failure, or cross-reactivity of the cTnI assay with non-cardiac antigens.

Adult↗
PubMed1996

Comparison of HPLC and GC-MS for measurement cocaine and metabolites in human urine.

High-performance liquid chromatography (HPLC) was compared with gas chromatography-mass spectrometry (GC-MS) for quantitation of cocaine, benzoylecgonine, norcocaine, and cocaethylene in urine. Calibration standards were prepared in human urine, and bupivacaine was added as the internal standard for quantitation. After solid-phase extraction, the reconstituted samples were divided into aliquots for analysis by HPLC and GC-MS. The analytical performance of the two methods were compared with regard to sensitivity, precision, and dynamic range. Results of GC-MS and HPLC analyses of nine urine specimens previously confirmed as positive for benzoylecgonine were compared. Analytical results by HPLC were comparable to GC-MS. Therefore, for many laboratories, HPLC is a useful alternative to GC-MS for measuring cocaine and metabolites in urine.

Chromatography, High Pressure Liquid↗
PubMed1994

Detection of cocaine exposure in the neonate. Analyses of urine, meconium, and amniotic fluid from mothers and infants exposed to cocaine.

Cocaine and its metabolites were measured in urine, meconium, and amniotic fluid specimens collected from 30 maternal-infant pairs with histories of prenatal cocaine use. Cocaine, benzoylecgonine, and ecgonine methyl ester were measured by isotope dilution gas chromatography-mass spectrometry. Mothers were interviewed at delivery regarding their cocaine use during pregnancy. There was qualitative agreement between the results of drug determinations in maternal urine, amniotic fluid, infant urine, and meconium. Although all of the mothers in this study admitted to using cocaine during their pregnancy, cocaine or its metabolites were detected only in the 20 cases in which cocaine was used within 3 weeks before delivery. We conclude that when sufficiently sensitive analytic methods are used, maternal urine, infant urine, and meconium analyses yield equivalent results for detection of prenatal cocaine exposure. Importantly, neither meconium nor urinary drug measurements detected cocaine exposure when the last reported use was prior to 3 weeks before delivery.

Adult↗
PubMed1989

A long-term intravenous model of aluminum maltol toxicity in rabbits: tissue distribution, hepatic, renal, and neuronal cytoskeletal changes associated with systemic exposure.

We studied the toxicity of an intravenously injected, water-soluble aluminum complex (aluminum maltol) in 20 young adult male New Zealand white rabbits over a period of 8 to 30 weeks. Sixteen rabbits injected with aluminum-free maltol and 15 untreated rabbits served as controls. Rabbits were injected three times per week with 75 mumol of aluminum maltol per injection, or a molar equivalent amount of maltol alone, through an indwelling jugular catheter. Liver contained the highest concentrations of aluminum among the aluminum maltol-treated rabbits, and aluminum accumulation was correlated with the appearance of periportal multinucleated giant cells in 13 of 20 rabbits. These cells stained positively for aluminum when a fluorescent (Morin) stain was applied to tissue from rabbits with a high concentration of aluminum in the liver. Proximal renal tubular necrosis or atrophy was found in 15 of 20 aluminum maltol-treated rabbits but not in maltol-treated and untreated controls. Renal tubules in rabbits with acute proximal renal necrosis stained positively for aluminum. Neurofibrillary tangles, immunoreactive with a monoclonal antibody to the 200-kDa subunit of neurofibrillary protein, were observed in the oculomotor nucleus of 3 aluminum maltol-treated rabbits (treated for 12, 20, and 29 weeks), but in none of the two groups of controls. These tangles were present in 3 of 10 aluminum-treated rabbits in which the nucleus was located. None of the 17 animals in both control groups in which the nucleus was found demonstrated tangles. A slight increase in brain tissue aluminum concentration was confirmed by an electrothermal atomic absorption spectrophotometric method. There were no specific findings in heart or lung tissue from aluminum-treated rabbits, although the aluminum content of these tissues was 10 to 20 times greater than control values. This model should be useful for investigating the effects of systemic exposure to high concentrations of solubilized aluminum.

Aluminum↗
PubMed1989

Ultrastructural localization of aluminium in liver of aluminium maltol-treated rabbits by laser microprobe mass analysis.

By means of laser microprobe mass analysis (LAMMA), we have studied the ultrastructural localization of aluminium in livers of aluminium maltol-treated rabbits. This animal model was developed to study long-term aluminium toxicity using systemic (intravenous) administration of aluminium. We could only detect aluminium in electron-dense inclusion bodies found in large, sometimes multinucleated cells. These results prove that the actual observation of aluminium deposits in liver with LAMMA gives more information than bulk analysis and can be very useful to explore mechanisms of toxicity.

Aluminum↗
PubMed1988

Aluminum.

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Aluminum↗
PubMed1988

Amylase in urine as measured by a single-step chromolytic method.

We studied a new single-step direct chromolytic method (Behring D.A.T.) for measuring urinary amylase (1,4-alpha-D-glucan glucanohydrolase, EC 3.2.1.1) activity, comparing results with those by a similar, but two-step, procedure that requires an auxiliary (coupling) enzyme. The two methods gave virtually identical relative responses to purified human pancreatic and salivary amylases. Assay of four quality-control materials to evaluate the total (day-to-day) precision of the new method yielded CVs of 4 to 7%, similar to those of the comparison method for each of the four quality-control samples. Amylase activity was measured by both methods in 110 random (i.e., untimed) urine specimens. Linear regression analysis provided a slope and y-intercept of 0.947 and 4 U/L (x = comparison method, y = direct method), respectively, and a standard error of the estimate of 25 U/L for specimens in which the amylase activities ranged from 11 to 1465 U/L (mean = 358 U/L) by the comparison method. The mean rate of amylase excretion in 2-h timed urine specimens from 95 healthy volunteers, as measured by the new method, was 7.18 (SD = 3.18) U/h, and the nonparametric (95% confidence interval) reference interval was 1.6 to 15.2 U/h. We consider the new method a promising alternative to other kinetic assays that require the use of auxiliary enzymes.

Amylases↗
PubMed1988

Lithium determined in serum with an ion-selective electrode.

We evaluated the performance of the lithium ion-selective electrode (ISE) in the Du Pont Na/K/Li analyzer. Lithium concentrations in 106 serum samples from patients being treated with lithium were measured in duplicate with the ISE and by flame photometry. The slope of the regression line for the two methods was 1.004 with a standard error of the estimate of 0.049 mmol/L (x = flame photometry, y = ISE). Lithium measurements by the ISE method in serum or aqueous standards were linear to greater than 2.0 mmol/L. Within-run CVs for low (0.31 mmol/L) and high (1.15 mmol/L) lithium controls were 5.9% and 1.7%, respectively (n = 20). Day-to-day CVs for the same controls were 9.8% and 3.3%, respectively (n = 20). There was no significant interference when the concentrations of sodium, potassium, calcium, or magnesium were varied, nor did intervening urinary lithium analyses affect the measurement of serum lithium. Results for lithium measurement in four serum-based survey materials compared well with results by isotope dilution/mass spectrometry.

Electrodes↗
PubMed1987

Aluminum and Alzheimer's disease: perspectives for a cytoskeletal mechanism.

A considerable volume of literature has accumulated concerning the association of aluminum with Alzheimer's disease. The pathogenic mechanisms resulting in Alzheimer's disease remain unknown, but recent investigations have focused on cytoskeletal abnormalities as perhaps the key lesion in Alzheimer's disease and related neurological disorders. The diversity of neuronal functions that are dependent on cytoskeletal integrity suggests that subtle effects on polymerization, assembly, transcription, or processing of cytoskeletal elements may have significant and far-reaching neurological effects. That aluminum may participate in the development of neuropathological lesions characteristic of Alzheimer's disease is suggested by evidence that aluminum is a potent cytoskeletal toxin, produces cognitive deficits in laboratory animals, and can be detected within abnormal neurons isolated from brain tissue from Alzheimer's disease patients. In this review, a critical look will be taken at the enigmatic role aluminum has played in Alzheimer's disease research, the possibility of its pathogenicity, and its use as a tool for the investigation of cytoskeletal changes that may result in the biochemical and, ultimately, clinical manifestations of Alzheimer's disease.

Aluminum↗
PubMed1987

Transferrin binding of Al3+ and Fe3+.

An understanding of Al3+-induced diseases requires identification of the blood carrier of Al3+ to the tissues where Al3+ exerts a toxic action. Quantitative studies demonstrate that the protein transferrin (iron-free) is the strongest Al3+ binder in blood plasma. Under plasma conditions of pH 7.4 and [HCO3-]27 mmol/L, the successive stability constant values for Al3+ binding to transferrin are log K1 = 12.9 and log K2 = 12.3. When the concentration of total Al3+ in plasma is 1 mumol/L, the free Al3+ concentration permitted by transferrin is 10(-14.6) mol/L, less than that allowed by insoluble Al(OH)3, by Al(OH)2H2PO4, or by complexing with citrate. Thus transferrin is the ultimate carrier of Al3+ in the blood. We also used intensity changes produced by metal ion binding to determine the stability constants for Fe3+ binding to transferrin: log K1 = 22.7 and log K2 = 22.1. These constants agree closely with a revision of the reported values obtained by equilibrium dialysis. By comparison with Fe3+ binding, the Al3+ stability constants are weaker than expected; this suggests that the significantly smaller Al3+ ions cannot coordinate to all the transferrin donor atoms available to Fe3+.

Aluminum↗
PubMed1986

Trace metals and degenerative diseases of the skeleton.

Aluminum related osteodystrophy is the most important manifestation of trace metal toxicity related to degenerative diseases of the skeleton. Aluminum overload occurs in chronic renal failure patients on hemodialysis treatment and results from transfer from dialysis solutions and from oral intake of aluminum containing phosphate binding gels. Laboratory diagnosis involves serum and bone analysis and bone staining for aluminum. A challenge test with desferrioxamine also aids in the diagnosis. Electrothermal atomic absorption spectrometry is widely used for aluminum detection. Guidelines for toxic concentrations of aluminum have been established.

Aluminum↗
PubMed1986

Absorption of aluminum from aceglutamide aluminum in healthy adult males.

The absorption of aluminum was studied in twelve healthy male volunteers over a period of fourteen days in a placebo-controlled, double blind study. All subjects were institutionalized during the study. Eight subjects (treated group) received ascending doses of aceglutamide aluminum (N-acetyl-L-glutamine aluminum complex) administered in multiple daily doses. The remaining four subjects (untreated group) received placebo. Systemic absorption and excretion of aluminum were evaluated by measuring aluminum concentrations in serum, urine and fecal samples. Aluminum concentrations were determined by electrothermal atomic absorption spectrometry. All serum aluminum concentrations were less than 16 micrograms/L for both groups. The mean urinary and fecal aluminum concentrations in the aluminum-treated group were significantly higher than in the untreated group during the study days the drug was administered. The total amount of aluminum (as aceglutamide aluminum) given to each treated subject during the 14 day study period as 3290 mg. The mean total fecal aluminum concentration was 3318 mg for the treated group and 269 mg for the untreated group during the study period. These findings are consistent with the view that some aluminum absorption from the gastrointestinal tract occurred following the administration of the drug. The absorbed aluminum appears to have been rapidly excreted in the urine and the feces.

Adolescent↗