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Biomedical subjects

M R Wills

Publications and source records attributed to M R Wills.

At least 55 records · Page 3Linked to original sources
PubMed1989

Isotope dilution gas chromatography/mass spectrometry for the determination of nickel in biological materials.

Precise and accurate methods are required to measure nickel in urine and serum samples to identify clinical states of either deficiency or toxicity. This paper presents an isotope dilution gas chromatography/mass spectrometry method for the measurement of nickel in biological samples. The method involves the preparation of a thermally stable and volatile nickel chelate using lithium bis(trifluoroethyl)dithiocarbamate as the chelating agent. Conditions were optimized for the digestion of the sample and quantitative preparation of chelate as well as the precise and accurate measurements of the isotope ratios using a capillary column gas chromatograph with a general purpose mass spectrometer. The memory effect between samples of different isotope ratios was evaluated and was found to be negligible. The quantitative accuracy of isotope dilution was validated by measuring nickel in the NIST freeze-dried urine reference material, SRM 2670, with comparison to the recommended value.

Chelating Agents↗
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↗
PubMed1989

Aluminum and chronic renal failure: sources, absorption, transport, and toxicity.

In normal subjects the gastrointestinal tract is a relatively impermeable barrier to aluminum with a low fractional absorption rate for this metal ion. Aluminum absorbed from the gastrointestinal tract is normally excreted by the kidneys; in the presence of impaired renal function aluminum is retained and accumulates in body tissues. Aluminum-containing medications are given, by mouth, to patients with chronic renal failure as phosphate-binding agents for the therapeutic control of hyperphosphatemia. Patients with chronic renal failure are also exposed to aluminum in domestic tap-water supplies used either for drinking or, in those on dialysis treatment, in the preparation of their dialysate. In patients with end-stage chronic renal failure, particularly in those on treatment by hemodialysis, the accumulation of aluminum in bone, brain, and other tissues is associated with toxic sequelae. An increased brain content of aluminum appears to be the major etiological factor in the development of a neurological syndrome called either "dialysis encephalopathy" or "dialysis dementia"; an increased bone content causes a specific form of osteomalacia. An excess of aluminum also appears to be an etiological factor in a microcytic, hypochromic anemia that occurs in some patients with chronic renal failure on long-term treatment with hemodialysis. The various mechanisms involved in the toxic phenomena associated with the accumulation of aluminum in body tissues have not been clearly defined but are the subject of extensive investigations.

Aluminum↗
PubMed1989

Tumoral calcinosis: seasonal biochemical studies and chemical studies of eyelid lesion.

We recently described (Arch Ophthalmol 1988; 106:725-6) the presence of unique calcific lesions in the eyelids of a young woman with a history of hyperphosphatemic tumoral calcinosis. Here we document that no immediate family members showed similar lesions and that none was hyperphosphatemic. Dental roentgenography revealed characteristic abnormalities in the patient that confirmed the clinical diagnosis of tumoral calcinosis. Seasonal biochemical studies demonstrated persistently increased concentrations of phosphorus and 1,25-dihydroxyvitamin D in her serum. A calcific eyelid excrescence removed from the patient, studied by x-ray diffraction, was found to consist of crystals of hydroxyapatite. Microprobe analysis indicated the major elements in the deposit to be Ca, P, S, and Cl, just as in the periarticular deposits found in tumoral calcinosis. The Ca concentration in the patient's tear fluid, measured by atomic absorption spectrometry, was within the range found in tears of healthy volunteers. Phosphorus was undetectable (less than 30 mumol/L) in tears of the patient and the volunteers. These findings suggest that the eyelid lesions represent a new manifestation of the pathological process that produces the characteristic periarticular calcific masses of tumoral calcinosis.

Adolescent↗
PubMed1989

Micro-quantity tissue digestion for metal measurements by use of a microwave acid-digestion bomb.

We describe a simple and convenient method for processing small amounts of tissue samples for trace-metal measurements by atomic absorption spectrometry, by use of a modified Parr microwave digestion bomb. Digestion proceeds rapidly (less than or equal to 90 s) in a sealed Teflon-lined vessel that eliminates contamination or loss from volatilization. Small quantities of tissue (5-100 mg dry weight) are digested in high-purity nitric acid, yielding concentrations of analyte that can be measured directly without further sample manipulation. We analyzed National Institute of Standards and Technology bovine liver Standard Reference Material to verify the accuracy of the technique. We assessed the applicability of the technique to analysis for aluminum in bone by comparison with a dry ashing procedure.

Aluminum↗
PubMed1989

Influence of matrix on concentrations of somatotropin measured in serum with commercial immunoradiometric assays.

Using immunoradiometric assays (IRMAs) from Hybritech Inc. (H) and Nichols Institute Diagnostics (ND), we measured somatotropin (human growth hormone, hGH) in serum samples obtained every 20 min for 24 h from 10 prepubertal subjects with short stature. Results obtained with the ND reagents were 2.74 times greater than those obtained with the H reagents (P = 0.00001, r = 0.94, SEE = 3.9, n = 720). We therefore compared the IRMAs with the standard hGH RIA from the National Institutes of Health (NIH) National Hormone and Pituitary Program, using the genetically engineered hGH preparations (from Genentech Inc.) 22-kDa hGH and methionated 20-kDa hGH. We also assayed human pituitary hGH (NIH, lot no. AFP-4793B). Each hGH preparation was diluted in three diluent buffer systems: horse serum from H and from ND, and human serum. The RIA and H-IRMA gave superimposable standard curves for all hGH preparations in each diluent. The methionated 20-kDa hGH was not detected in the H-assay. Use of human serum matrix in the ND-IRMA shifted the standard curve as compared with the horse-serum matrix, giving equivalent binding at lower concentrations; i.e., serum hGH was overestimated in samples assayed against standards diluted in horse serum. Quality-control materials (Ciba-Corning) yielded disparate results in all three assays, yet human serum pools containing hGH gave similar results in the H and the NIH assays, and higher values in ND. When a human serum standard was used in the ND assay, both IRMAs gave similar results to the RIA assay for human serum samples. Reference intervals for hGH should be determined by each analytical laboratory, to prevent misdiagnosis of patients. Furthermore, quality-control material should be of human origin, because commercially supplied quality-control material does not react the same as human serum in some hGH assays.

Child↗
PubMed1989

Normal biochemical and hematological values in New Zealand white rabbits.

Animal model systems are used extensively for experimental in vivo studies. When biochemical and hematological measurements are made, reference intervals for the animal species must be determined. Here, the subjects for our study were young adult male New Zealand White rabbits. Blood was sampled from 110 normal healthy rabbits. Biochemical and hematological blood variables were measured by methods available in our routine service laboratory, and we report the ranges.

Alkaline Phosphatase↗
PubMed1988

Aluminum.

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Aluminum↗
PubMed1988

Aluminum metabolism in rats: effects of vitamin D, dihydrotachysterol, 1,25-dihydroxyvitamin D and phosphate binders.

In order to study the effects of vitamin D on aluminium balance when different forms of vitamin D and phosphate binders are used simultaneously for therapeutic purposes, 30 Sprague-Dawley weanling rats, weighing 44-66 g, were randomly assigned to 5 groups: (A) control, (B) aluminum hydroxide, (C) dihydrotachysterol at 16 micrograms/kg/day, (D) 1,25-dihydroxyvitamin D at 16 ng/kg/day and (E) vitamin D at 2,000 IU/kg/day. Aluminum hydroxide (60 mg/kg/day) in the feed was provided to all except the control group. The vitamin D or metabolites were fed by stomach tube daily for a period of 10 days. At the end of the study, the mean (+/- SEM) serum aluminum concentration, as determined by flameless atomic absorption spectrophotometry, was 5.0 +/- 2.4 micrograms/l; there were no significant differences in these results between groups. During the last three days of the study, 24-hour urine and stool collections were made with the usual precautions against trace mineral contamination. The means (+/- SEM) of aluminum balances for groups A, B, C, D and E were -388 +/- 261, 1,121 +/- 331; 2,316 +/- 304; 2,387 +/- 245, and 1,968 +/- 337 micrograms/day, respectively. We conclude that at therapeutic doses of aluminum hydroxide and vitamin D or its metabolites, hyperaluminemia was not observed. However, the positive aluminum balances imply retention, and the use of vitamin D, especially its potent metabolites dihydrotachysterol and 1,25-dihydroxyvitamin D, intensified this risk.

Aluminum↗
PubMed1988

Measurement of cholesterol in serum by gas chromatography/mass spectrometry at moderate mass resolution, with a nonendogenous cholesterol isomer as internal standard.

We describe a gas chromatography/mass spectrometry method for the quantitative analysis of cholesterol in serum. A structural isomer of cholesterol, 7,(5 alpha)-cholesten-3 beta-ol, is used as an internal standard, its primary advantage being its lesser cost relative to that of a stable-isotope-labeled analog. Analysis of the National Bureau of Standards Certified Reference Serum (SRM 909) was used to validate the method. The results show this method to be highly accurate (bias = -0.6%) and precise (CV = 1.6% between-run, 1.2% within-run). The performance of this method is, therefore, sufficiently good to allow its use as a reference method for determinations of cholesterol in serum.

Cholesterol↗
PubMed1987

Limitation of deuterium labelled methoximes as internal standards in the mass spectral analysis of prostaglandins.

A reported method for the preparation of d3-methoxime derivatives as internal standards for prostaglandin assays by gas chromatography-mass spectrometry was evaluated. Sample derivatization resulted in 1.5-86% exchange of the d3-methoxime in a series of prostaglandins. Exchange was minimal when the methoxime was on the 5-membered ring; whereas, acyclic methoximes exhibited extensive exchange. Induced strain energy due to the steric interaction of the hydroxyl group and the C13-C20 alkyl side chain with the gem-dimethoxylamine transition state is offered as an explanation for the unusual stability of PGE2. The use of 18O exchange of the carboxylic acid function is presented as an alternative for the preparation of unavailable labelled eicosanoids.

Deuterium↗
PubMed1987

Aluminum deposition in the central nervous system. Preferential accumulation in the hippocampus in weanling rats.

Simultaneous administration of 1,25-dihydroxyvitamin-D3, citrate, and aluminum-containing phosphate binders is frequently used in patients with chronic renal failure. In order to investigate whether citrate may represent a risk factor of aluminum intoxication, 16 Sprague-Dawley weanling rats were randomly assigned to four groups: 1,25-dihydroxyvitamin-D3 at 16 ng/kg/day was given to all groups except the control; in addition, two groups received either aluminum hydroxide at 160 mg elemental aluminum/kg/day, or aluminum citrate at 160 mg elemental aluminum/kg/day, respectively. The control group received only the vehicle. Extremely high aluminum concentrations were detected in the hippocampus of rats receiving aluminum compounds. This content of aluminum (microgram/g dry weight) was far higher than that found in other brain areas of the same animals (146.40 +/- 51.23 versus 4.49 +/- 0.62, P less than 0.001) as well as that detected in the hippocampus of the control animals (2.73 +/- 0.40). Thus, in non-uremic, weanling rats supplemented with 1,25-dihydroxyvitamin-D3, the administration of aluminum favors selective accumulation in the hippocampus. No differences between aluminum hydroxide and aluminum citrate administration were observed.

Aluminum↗