Diagnostic X-ray Spectrometry Research Articles

Measurement of breast skin viscoelasticity and a pilot study on the potential radioprotective effect of a zinc-based cream.

Radiation-induced late skin effects were studied in patients with breast cancer in relation to different protocols of fractionated radiotherapy in three different medical centres, in Israel, the UK and the USA. The mechanical properties of skin were evaluated in breasts of healthy volunteers, and non-irradiated and irradiated breasts of patients, using a newly developed viscoelasticity skin analyser (VESA). The increase of the dose of radiation per fraction was found to have more impact on the development of radiation-induced late skin effects than the elevation of the total dose given. In addition, a pilot study on the possible radioprotective effect of external application of a cream containing zinc oxide on radiation-induced early skin changes in patients with breast cancer was initiated. Non-invasive measurement of trace elements and zinc pharmacokinetics in the skin of healthy controls following the application of the zinc oxide cream were performed by unique diagnostic X-ray spectrometry (DXS). Application of the cream, followed by thorough skin cleansing, significantly increased the amount of residual zinc in the skin, but continuous daily treatment did not cause further build-up of the dermal zinc level. The radioprotective effect of the zinc oxide cream on the skin is now being studied.

Noninvasive follow-up of platinum pharmacokinetics in the skin of patients on cisplatin chemotherapy

Treatment with high-dose cisdiammine-dichloroplatinum (II) (cisplatin, cDDP) often is associated with late complications, predominated by peripheral neuropathy. Pt deposition in different tissues may play a key role in the induction of many of these effects. Main topics of interest include the relationship between cDDP doses given during treatment and the long-term pharmacokinetics of the drug complexes in normal tissues and blood. Noninvasive examination of Pt in tissues during and after cDDP treatment are needed to clarify these points. A novel, high-sensitivity diagnostic x-ray spectrometry (DXS) method was used for the fast, noninvasive analysis of Pt in external tissues of patients with cancer treated with courses of cDDP. The Pt in a small skin area was excited by a monochromatic soft x-ray beam (14.6 KeV) and the spectral L lines emitted from the tissue were detected. A limit of detection below 1 microgram/g wet weight was reached. The pharmacokinetics of Pt in blood was investigated in parallel with the use of high-sensitivity, flameless atomic absorption spectrometry (AAS). Follow-up of Pt concentrations in the skin of patients with cancer by DXS before cDDP treatment, during treatment, and up to 4 months after its completion, showed prolonged Pt deposition that corresponded to the net cumulative doses of the drug. Pt clearance from the skin fitted a monoexponential curve with a half-life of about 30 days. In comparison, the pharmacokinetics of total Pt in plasma showed a much faster, biexponential clearance with half-lives of 41 minutes and 5.2 days, respectively. The amount of nonspecific Pt deposition in the tissues was found to depend on the total doses administered, the time interval between the courses, and the slow rate of clearance. Noninvasive measurements of tissue Pt levels may serve as a major tool in the evaluation of the induction of late cDDP complications.

A sensitive noninvasive analysis of Pt in external tissues. Followup of Pt deposition following cisplatin treatment.

Noninvasive analysis of heavy elements in external tissues by diagnostic-x-ray spectrometry (DXS) is presented. Pt can be detected accurately with sensitivity below 1 microgram/g wet weight of tissue. In the present paper the possibility to monitor Pt accumulation and clearance in the external tissues of cancer patients treated with cisplatin [Cis-diamminedichloroplatinum (II)-cDDP] chemotherapy is reported. The DXS method is based on x-ray fluorescence analysis. Heavy elements in the small skin area of interest are analyzed by their excitation with a monochromatic soft x-ray beam of 14.6 KeV. Spectral L lines of heavy metals such as Pt are detected with minimum interference by other elements in the tissues. Skin Pt levels up to about 6 micrograms/g were observed following several courses of cDDP treatment. The Pt seemed to be homogeneously distributed in different skin areas with similar levels in the dermis and epidermis. The rate of clearance of Pt from the skin (50% in about 30 days) was slower by three orders of magnitude than its clearance from plasma. Further studies may use DXS to establish the accurate kinetics of Pt deposition and clearance in tissues of cDDP treated patients, as well as the exact relation between tissue Pt levels and the development of the drug related late complications.

Platelet multielemental composition, lability, and subcellular localization

Diagnostic X-ray spectrometry (DXS), based on X-ray fluorescence, was used to quantitate directly the multiple elemental composition of washed, intact human platelets (n = 16), with the following results: K = 3.08 +/- 1.00 mg/g, Ca = 1.18 +/- 0.29 mg/g, Zn = 35 +/- 9 micrograms/g. These values show that washed platelets contain significant pools of K, Ca, and Zn, the latter some 30-60-fold higher than plasma levels. Dialysis of whole platelets against cation exchange resin (Chelex-100) did not extract Ca(II) and Zn(II) sequestered within whole cells. To identify the subcellular locale of the elements, platelet lysate was subjected to 30-70% sucrose gradient ultracentrifugation and subcellular enriched fractions were obtained. Fractions were analyzed by DXS (for elements), electron microscopy (for dense granules), and subcellular markers fibrinogen and von Willebrand factor. In contrast to Ca and K, which accumulate in the dense granules and the cytoplasm, respectively, Zn appears to be distributed in the alpha-granules (40%) and the cytoplasm (60%). The subcellular distribution of Zn(II) is discussed within the context of the sensitivity of platelet response to the availability of Zn(II) and the platelet release reactions following stimulation.

A long-term follow-up of metallic intraocular foreign bodies, employing diagnostic x-ray spectrometry.

We describe 10 eyes harboring metallic intraocular foreign bodies (IOFBs) for 9 to 46 years that had undergone diagnostic x-ray spectrometry to measure metal dissolution 9 years before this study. Findings from the present clinical and laboratory examinations, including perimetry, electroretinography, electrooculography, and diagnostic x-ray spectrometry examinations are reported. Deterioration in visual acuity consequent to metal dissolution of the IOFB was found in only one eye. Visual fields and electrophysiologic performances deteriorated in two other eyes for reasons that were probably unrelated to IOFB dissolution. Visual functions remained stable during the follow-up period in seven eyes, although excess copper levels were demonstrated in one of them. Eight of 10 eyes retained visual acuity of 6/24 or better. Diagnostic x-ray spectrometry confirmed siderosis in one patient and ruled out metallosis in the two patients with deteriorated vision for reasons that were unrelated to metallosis. The favorable outcome of this series of patients may influence one to consider a more conservative approach in the decision to remove IOFBs. A careful, life-long follow-up might be considered with periodic electroretinographic and diagnostic x-ray spectrometry examinations; the IOFB should be promptly removed if and when metallosis with damage to visual functions is demonstrated.

Skin Zinc Concentrations in Patients with Varicose Ulcers

The concentration of zinc in the skin has been determined noninvasively in patients with varicose vein ulcers. The examinations were performed with the use of diagnostic x-ray spectrometry, a method based on x-ray fluorescence for in vivo noninvasive evaluation of trace elements. Four skin foci were examined: at the periphery of the ulcer and control areas in a nonulcerated area in the diseased leg, in the noninvolved leg, and in the proximal inner surface of the arm. Zinc levels around the ulcer (mean +/- SD, 9.8 +/- 4.0 micrograms of zinc in 1 g of wet tissue) were higher than those in the nonulcerated skin in the diseased leg (6.9 +/- 3.0 micrograms/g, p greater than 0.05) and those in the noninvolved leg (5.4 +/- 2.0 micrograms/g, p less than 0.01). The concentration of zinc in the inner proximal surface of the arm (9.8 +/- 2.8 micrograms/g) was significantly higher than those of a control group (5.3 +/- 1.9 micrograms/g, p less than 0.01). These results suggest a defect of zinc distribution in patients with varicose vein ulcers.

Overload of Iron in the Skin of Patients With Varicose Ulcers

The brown pigmentation of the skin associated with venous ulceration is caused by increased local iron deposition. Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for the noninvasive determination of iron levels in the skin of patients with venous ulceration. The mean (+/- SEM) iron concentration in the skin around the venous ulcer was elevated, compared with control values of nonulcerated skin (250 +/- 54 vs 128 +/- 39 micrograms) and compared with normal skin from the forearm (250 +/- 54 vs 14 +/- 2.5 micrograms). These data suggest that dermal iron deposition may not be an incidental by-product of increased venous pressure, but may actively perpetuate tissue damage in venous ulcerations.

Noninvasive assessment of skin iron content in hemodialysis patients. An index of parenchymal tissue iron content?

Iron overload has been described in patients undergoing chronic hemodialysis. The present study was undertaken to evaluate a rapid, noninvasive method for determination of skin iron by the technique of diagnostic x-ray spectrometry (DXS). Thirty-five patients receiving chronic hemodialysis treatment entered the study and were compared with 25 normal controls. Since pathological skin iron deposition occurs mainly at the dermal-epidermal junction in the basal cells of the epidermis, measurements were made in the thenar eminence representing mainly epidermal tissue (FeE), and in the forearm representative mainly of dermis (FeD). The mean +/- SD FeE iron concentrations were equivalent to 14.5 +/- 8.8 and 18.2 +/- 10.2 parts per million wet weight tissue (ppm) and both were significantly higher than in normal controls in which they averaged 9.2 +/- 2.5 ppm (P less than 0.005) and 10.2 +/- 3.2 ppm (P less than 0.001), respectively. There was significant positive correlation between individual skin iron determinations with the total number of blood transfusions received, the rate of blood transfusion, and with serum ferritin levels. Bone marrow hemosiderin was examined in six patients and showed a similar trend. Despite correlation only with indirect indices of tissue iron, our findings suggest that DXS may serve as a reliable quick method for noninvasive estimation of nonreticuloendothelial tissue iron deposition in hemodialysis patients suspected of having transfusional iron overload. The method may be valuable in monitoring the effects of chelation therapy.

Iron, copper, and zinc concentrations in normal skin and in various nonmalignant and malignant lesions.

The concentrations of zinc (Zn), copper (Cu), and iron (Fe) in the skin have been noninvasively determined in vivo by diagnostic x-ray spectrometry. The skin of healthy controls was divided into two major groups based upon the distribution of the concentrations of these elements. In the face and upper neck, the following wet weight concentrations were recorded: Fe, 14.2 +/- 3.3 ppm; Cu, 1.3 +/- 0.3 ppm; and Zn, 6.7 +/- 1.1 ppm. In the chest, abdomen, arm, axilla, and lower neck, the concentrations of these elements were as follows: Fe, 10.2 +/- 2.5 ppm; Cu, 0.8 +/- 0.3 ppm; and Zn, 4.5 +/- 1.7 ppm. In most lesions of solar dermatitis, solar keratosis, basal and squamous cell carcinomas, variable elevations of Zn and Fe (up to significant levels) were recorded in most of the contralateral, apparently uninvolved skin. In the majority of pigmented nevi and malignant melanomas, the levels of Fe and Zn were elevated. In some of these, the Cu concentration also was increased.

Correlation of erythrocyte and plasma levels of zinc, copper, and iron with evidence of metastatic spread in cancer patients.

The level of plasma copper (Cu-Pl) and zinc (Zn-Pl) and the level of erythrocyte iron (Fe-RBC), copper (Cu-RBC), and zinc (Zn-RBC) were determined in the blood of 70 normal donors and 138 patients with various solid tumors by diagnostic x-ray spectrometry (DXS), a technique based on x-ray fluorescence spectrometry analysis. There were no significant changes in the mean values of Zn-Pl, Fe-RBC, and Cu-RBC in the patients when compared with those of normal donors. The mean level of Cu-Pl in the normal donors was 1.34 +/- 0.37 micrograms/ml; it was significantly increased in the patients, ranging between 1.47 +/- 0.34 micrograms/ml for patients without evidence of active cancer (NED) and 1.91 +/- 0.76 micrograms/ml for patients with hepatic metastases. The most significant change observed was an increase in the Zn-RBC found in the patients with clinical evidence of metastatic spread. Whereas the Zn-RBC level in the normal donors was 9.85 +/- 1.47 micrograms/g wet weight, and not significantly elevated in the NED patients, it was elevated to values of 11.37 +/- 1.55 micrograms/g (P less than 0.004) for patients with soft tissue and hepatic metastases and was 12.34 +/- 1.65 micrograms/g (P less than 0.001) for patients with bone metastases. The data suggest a clear correlation between Zn-RBC and metastatic spread in nonlymphomatous human cancer.

Noninvasive analysis of skin iron and zinc levels in beta-thalassemia major and intermedia.

Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for noninvasive determination of iron and zinc in two distinct skin areas, representing predominantly dermal and epidermal tissues, in 56 patients with beta-thalassemia major and intermedia. The mean iron levels in the skin of patients with beta-thalassemia major and intermedia were elevated by greater than 200% and greater than 50%, respectively, compared with control values. The zinc levels of both skin areas examined were within the normal range. The data indicate that the rate and number of blood transfusions, which correlated well with serum ferritin levels (r = 0.8), are not the only factors that determine the amount of iron deposition in the skin (r less than 0.6). Other sources of iron intake contribute to the total iron load in the tissues, particularly in patients who are not given multiple transfusions. The noninvasive quantitation of skin levels may reflect the extent of iron deposition in major parenchymal organs. Repeated DXS examinations of the skin could monitor the clearance of iron from the tissues of patients with iron overload in the course of therapy with chelating agents.

In vivo study of trace elements in leprous skin.

The skin of leprous patients at various stages of the disease was investigated by diagnostic x-ray spectrometry, In the active stage raised iron and slightly raised zinc levels were found. The usefulness of the method in skin investigation is foreseen.