Histology and platinum content of sensory ganglia and sural nerves in patients treated with cisplatin and carboplatin: an autopsy study.

Cisplatin is a valuable antineoplastic drug which as a dose-limiting side-effect causes sensory neuropathy, and which therefore is often combined with less neurotoxic carboplatin. It has not been possible to reproduce cisplatin neuropathy in experimental animals, and the neurotoxic mechanism in man is disputed. We investigated post-mortem material from 12 patients and 15 control subjects. Half of the fibres with diameters of > or = 9 microns, or more than 15% of all fibres (P < 0.02), had disappeared in the sural nerves of patients. Signs of axonal regeneration were lacking. The dorsal root ganglia D12 and L2 of some but not of all patients contained necrotic neurons and nodules of Nageotte. The mean volume of the somata was reduced by 18% (P < 0.03). A relation between cumulated doses, treatment free interval and changes in nerve or ganglia was not found. The platinum content was high in all tissues except in the spinal cord when the patient had died shortly after treatment, and it decreased with increasing interval, least so in liver, sensory ganglia and sural nerves. The results support the hypothesis that cisplatin neuropathy is a neuroneopathy rather than a dying-back axonopathy.

Accumulated experience with prenatal diagnosis of Menkes disease by neutron activation analysis of chorionic villi specimens.

Since 1983, prenatal diagnosis of Menkes disease has been carried out by determining Cu in samples of chorionic villi from the fetus by means of radiochemical neutron activation analysis. Concentrations of Cu in chorionic villi from male fetuses later confirmed to have Menkes disease were invariably higher than previously reported values for normal controls. Out of 240 samples analyzed in the period 1983-1998, there were 71 from female fetuses that could be carriers of the Menkes genetic defect without suffering from the disease. Increased concentrations of Cu in these samples could not be attributed to the presence of this genetic defect, but might result from sporadic contamination of the samples before analysis. Such contamination also may occur in samples from male fetuses and thus raise the level of Cu in small, but normal specimens into the range characteristic of Menkes disease. In spite of a strict protocol for taking samples without contamination, a total of four false positives were reported during the period of investigation; no false negatives have occurred.

Determination of platinum by neutron activation analysis in nerve tissue from rats treated with cisplatin.

The analytical method used for the determination of traces of platinum and gold in different tissues of Wistar rats is based on neutron activation analysis with radiochemical separation of gold. This separation is performed by electrolytic deposition of gold on a niobium cathode, which ensures the highest radiochemical purity without any spectral interference from calcium or other major elements. Corrections for the nuclear interference from double neutron capture, caused by the gold content of the samples, were found to be insignificant at the levels reported. The following neural tissues were analyzed for their content of platinum: the dorsal root ganglions as well as the dorsal and ventral part of the spinal cord. The highest level of platinum was found in dorsal root ganglions.

A dental technician with pulmonary fibrosis: a case of chromium-cobalt alloy pneumoconiosis?

A 45 yr old male developed pulmonary fibrosis after 29 yrs of employment as a dental technician. He subsequently developed adenocarcinoma of the lung. Diffuse interstitial fibrosis was seen using light microscopy. Neutron activation analysis of non-neoplastic lung tissue demonstrated high levels of chromium and cobalt suggesting the possibility of a chromium-cobalt alloy pneumoconiosis.

Intake of essential and toxic trace elements in a random sample of Danish men as determined by the duplicate portion sampling technique.

Average daily intakes of essential and toxic trace elements from self-selected diets consumed by 100 men, selected as a random sample among the population of 30-34 year-old men in one urban and two rural areas of Denmark, were determined by the analysis of 48 h duplicate food portions. Median daily dietary intakes were 11.3 mg for zinc, 1.1 mg for copper, 11.3 mg for iron, 51 micrograms for selenium, 3.9 mg for manganese, 99 micrograms for molybdenum, 7 micrograms for lead and 11 micrograms for cadmium. Median dietary intake of mercury was below the detection limit. The observed nitrogen, sodium and potassium intakes were about 25% lower than the average total daily excretion of these constituents. It is therefore assumed that dietary intakes of nutrients during the duplicate portion sampling period were reduced by about 25% and that the observed intakes of trace elements can be regarded as minimum estimates of habitual intake. Taking this into consideration, it is concluded that the content of essential trace elements in Danish diets seems to be adequate and the amounts of the elements lead, mercury and cadmium are of little concern as regards health aspects.

Factors affecting the levels reported for vanadium in human serum.

Chemometric techniques may be applied to extract significant analytical information from a series of publications that present methods and results for determining trace elements in biological material. This approach was applied to the total of 28 papers published in 1971-1988 that reported determination of vanadium in normal human serum or plasma; the levels spanned four orders of magnitude. The most important factors affecting the analytical results were found to be the choice of analytical method and the experience of the laboratory in trace-element research. Results from the most experienced laboratories with the best analytical methods were found to be correlated with the precision of the data, indicating that the correct concentration of vanadium would be less than 1 mg/m3. This is in agreement with results subsequently obtained by radiochemical neutron activation analysis of eight samples of serum from Danish colleagues.

Gains or losses of ultratrace elements in polyethylene containers.

The extent of elimination of losses and reduction of blank values in ultratrace elemental analysis can only be ascertained by comprehensive investigations for each element separately. Different, and partially conflicting precautions are found to be needed in the determination of manganese, copper, selenium, and mercury by neutron-activation analysis when polyethylene irradiation containers are used.

Distribution of arsenic, manganese, and selenium in the human brain in chronic renal insufficiency, Parkinson's disease, and amyotrophic lateral sclerosis.

The concentrations of arsenic, manganese and selenium/g wet tissue weight were determined in samples from 24 areas of the human brain from 3 patients with chronic renal insufficiency, 2 with Parkinson's disease and 1 with amyotrophic lateral sclerosis. The concentrations of the 3 elements were determined for each sample by neutron activation analysis with radiochemical separation. Overall arsenic concentrations were about 2.5 times higher in patients with chronic renal failure than in controls, and lower than normal in the patients with Parkinson's disease and amyotrophic lateral sclerosis. There were no obvious differences in the overall concentrations of manganese and selenium from one group to another. Even multivariate data analysis by the SIMCA method failed to reveal any significant difference in the distribution pattern of manganese and selenium in Parkinson's disease compared to normal controls.

Topographical distribution of arsenic, manganese, and selenium in the normal human brain.

The concentrations of arsenic, manganese and selenium per gram wet tissue weight were determined in samples from 24 areas of normal human brain from 5 persons with ages ranging from 15 to 81 years of age. The concentrations of the 3 elements were determined for each sample by means of neutron activation analysis with radiochemical separation. Distinct patterns of distribution were shown for each of the 3 elements. Variations between individuals were found for some but not all brain areas, resulting in coefficients of variation between individuals of about 30% for arsenic, 10% for manganese and 20% for selenium. The results seem to indicate that arsenic is associated with the lipid phase, manganese with the dry matter and selenium with the aqueous phase of brain tissue.

Simultaneous determination of arsenic, copper, manganese, selenium, and zinc in biological materials by neutron activation analysis.

A method for the simultaneous determination of arsenic, copper, manganese, selenium, and zinc in biological material was developed by the incorporation of separation procedures for copper and zinc into an existing procedure. Investigation of the performance characteristics of the method was carried out with reference to copper and zinc. For certain materials characterized by a high Cu/Zn ratio, or a high zinc content, or both, such as liver, copper interferes in the determination of zinc thus requiring a small correction by an iterative procedure. Blank values for copper depend on the rinsing of the irradiation container, and a single rinsing with redistilled water was found superior to other rinsing procedures. Nuclear interference was negligible. The accuracy of the method was checked by analysis of Standard Reference Materials and the precision verified by analysis of Intercomparison Samples. Results are presented for 5 male foetuses of 3-5 months' gestational age. The distribution of arsenic, manganese and selenium is similar to that previously reported for adults. With the exception of liver, concentrations of copper in foetal organs were lower than values in the literature indicate.

Analysis of precision of activation-analysis methods.

The precision of an activation-analysis method prescribes the estimation of the precision of a single analytical result. The adequacy of these estimates to account for the observed variation between duplicate results from the analysis of different samples and materials, is tested by the statistic T, which is shown to be approximated by a chi(2) distribution. Application of this test to the results of determinations of manganese in human serum by a method of established precision, led to the detection of airborne pollution of the serum during the sampling process. The subsequent improvement in sampling conditions was shown to give not only increased precision, but also improved accuracy of the results.