Metal exposure from amalgam alters the distribution of trace elements in blood cells and plasma.

Twenty-seven consecutive patients with health problems associated with dental amalgam were recruited. In spite of thorough medical examinations, there were no diagnoses available. The patient group was dominated by women. A healthy age- and sex-matched control group with dental amalgams without symptoms was also recruited. Metal level monitoring in plasma and nuclear microscopy of isolated individual blood cells were carried out. Significant increases of copper, iron, zinc and strontium were found in patient plasma. There was no significant difference in plasma selenium between the groups. Mercury was significantly increased in patient plasma, although there was overlap between the groups. In erythrocytes a significant increase in calcium and a significant decrease in magnesium, copper, manganese and zinc were found. Calcium, magnesium, manganese and copper increased in patient neutrophil granulocytes. A significant decrease was found for zinc. A conspicuous finding was the presence of measurable mercury in a few of the cells from the patient but not in the control group. Thus, nuclear microscopy of isolated individual blood cells might provide a better diagnostic tool for metal exposure than blood plasma measurements.

Mercury intolerance in relation to superoxide dismutase, glutathione peroxidase, catalase, and the nitroblue tetrazolium responses.

Through percutaneous provocation with metallic mercury and phenyl mercuric acetate in patients stating the presence of subjective psychosomatic symptoms following dental amalgam treatment, it has been possible to categorize and score two extreme groups of patients, mercury-intolerant and mercury-tolerant patients reacting and not reacting, respectively, to low doses of mercury. The intolerant patients had a high psychosomatic score and the tolerant patients had a low or null score when exposed to low doses of the two mercury compounds. Determination of the scavenger enzymes superoxide dismutase, glutathione peroxidase, and catalase showed no significant differences between the mercury-intolerant and the mercury-tolerant patients and the controls. The activity of superoxide dismutase and the quantitative psychosomatic score elicited by either metallic mercury or phenyl mercuric acetate showed a positive correlation. On the other hand, analyses of the psychosomatic score and the areas under the curves of the nitroblue tetrazolium test response showed negative correlations. The results indicate that the oxidative metabolism and, in particular, superoxide dismutase may be perturbed in mercury-intolerant patients.

Mercury content in amalgam tattoos of human oral mucosa and its relation to local tissue reactions.

Mucosal biopsies from 48 patients with and 9 without amalgam tattoos were analysed with respect to their mercury content, distribution of mercury in the tissue, and histological tissue reactions. The distribution of mercury was assessed by autometallography (AMG), a silver amplification technique. The mercury content was determined by energy dispersive X-ray fluorescence (EDXRF), a multielemental analysis. Mercury was observed in connective tissue where it was confined to fibroblasts and macrophages, in vessel walls and in structures with the histological character of nerve fibres. A correlation was found between the histopathological tissue reaction, the type of mercury deposition, the intensity of the AMG reaction, and the mercury content. Mercury was also found in patients with amalgam dental fillings but without amalgam tattoos.

Analysis of the metal content of in vivo-fixed dental alloys by means of a simple office procedure.

The purpose of this study was to devise a simple technique to analyse the metal content of permanent dental prostheses without damaging the constructions. Metal debris was collected on grinding wheels for subsequent analysis by energy-dispersive X-ray fluorescence (EDXRF). We discuss the importance of being able to qualitatively ascertain the composition of the alloys, as such information makes it possible to perform a detailed allergological investigation. Furthermore, we tentatively put our findings in a broader context with regard to the emerging knowledge of the relationship between the immune and central nervous systems as well as the known fact that certain metal ions can produce various cutaneous reactions.

Markers for vulnerability in acute porphyria. A hypothesis paper.

Previously symptomatic and permanently asymptomatic carriers of a gene mutation for acute intermittent porphyria as well as matched controls were screened with regard to a series of variables of possible relevance to the development of porphyric symptoms. The basis for the study was a concept of acute porphyria as a condition of a permanent system overload of oxidative stress, with long term effects on hepatic and renal tissue, and with instances of periodic overload of free radicals giving rise to acute neurologic involvement. Leukocyte concentrations of manganese, calcium, iron and zinc, as well as erythrocyte calcium differed between the groups, acute intermittent porphyria gene carriers, irrespective of previous porphyric illness, showing significantly higher levels than the controls. Manganese was found to be the most discriminative component of all the 78 variables investigated, accounting for about 98 per cent of the variance between the groups. An increment, by a factor of four, in cellular manganese is suggestive of an increase, in acute intermittent porphyria, of a manganese associated enzyme, e.g. glutamine synthetase, pyruvate carboxylase or mitochondrial superoxide dismutase. The best fit into the model considered is provided by a theory focused on superoxide dismutase, induced in response to superoxide anion radical produced from aminolaevulinic acid. In porphyria gene carriers seemingly resistant to porphyric manifestations, an increase in potentially prooxidant cellular iron is matched by a proportional increment in manganese, i.e. presumably by a corresponding mitochondrial superoxide dismutase induction. This mechanism is not operative in porphyric individuals prone to development of neuropsychiatric symptoms. In acute intermittent porphyria with a history of porphyric illness there is a positive correlation between erythrocyte manganese and serum folate and a negative correlation between leukocyte ferrochelatase activity and serum cobalamin concentration. This may mirror a role of the cobalamin-folate system in the acute porphyric process.

Total body potassium, fat and water during total parenteral nutrition in Crohn's disease.

The body composition was studied by measurement of body weight (BW) and total body potassium (TBK), fat and water in 13 patients with Crohn's disease (CD), who were given altogether 18 courses of total parenteral nutrition (TPN) with nil by mouth each lasting at least 3 weeks. At the start of TPN, one group of steroid-free patients displayed intracellular potassium depletion, as reflected by the ratio TBK/lean body mass (LBM) (group 1). Another group of steroid-free patients showed no depletion of intracellular potassium (group 2). The patients given prednisolone all showed intracellular potassium depletion and were assigned to a separate group (group 3). During the initial 19-44 days of TPN, TBK, LBM and BW increased in group 1. All patients with intracellular potassium depletion (groups 1 + 3) showed an increase in TBK and TBK/LBM during the initial 19-51 days of TPN. For steroid-free patients (groups 1 + 2) there were linear relationships between the rate of energy supply per kg LBM and the 24 h change in BW during the third and fourth weeks of TPN (r = 0.79) and between the 24 h change in BW and LBM during the first 19-44 days of TPN (r = 0.59). A steady state in BW was found on administering 53 kcal/kg LBM/24 h. It is concluded that CD patients with intracellular potassium depletion are likely to be improved in terms of TBK and TBK/LBM by at least 3 weeks of TPN as given in the present study. Steroid-free CD patients with intracellular potassium depletion are, moreover, likely to show an improvement in LBM by at least 3 weeks of TPN, and an increase in their BW during the initial 3-6 weeks of TPN will probably reflect an increase in LBM. The pre-TPN TBK/LBM ratio may be a predictor of the repletion rate of the LBM compartment during TPN of steroid-free wasted CD patients.

Selenium in whole blood and plasma is decreased in patients with moderate and severe psoriasis.

Concentrations of selenium in whole blood and plasma in 113 patients with moderate to severe psoriasis were compared with those in 104 healthy reference subjects. Most of the patients (85%) had had their psoriasis for at least 10 years and all had previously been treated with PUVA baths. Selenium concentrations both in whole blood and plasma were decreased both in male and female psoriasis patients. Male psoriatics 20-49 years old and women with disease of long duration (greater than 20 years) had particularly low selenium concentrations in whole blood. The lowest whole blood values were found in a subgroup of male patients with widespread disease of long duration who had also required treatment with methotrexate and/or retinoids to control their disease. The blood selenium in patients who also had psoriatic arthritis or arthralgia did not differ from those without such symptoms.

Urinary excretion and blood concentrations of trace elements and electrolytes during total parenteral nutrition in Crohn's disease.

Urinary excretion of trace elements (Cr, Co, Cu, Fe, Mn, Se, Zn, Sb, Cs, Rb), electrolytes (Na, K, Ca, Mg, phosphate), and nitrogen were determined during days 1-5 and 54-79 of total parenteral nutrition (TPN, nil per os) given to six patients with Crohn's disease. Whole-blood concentrations of Cr, Fe, Zn, Cs, and Rb and serum concentrations of electrolytes were determined before the TPN and on days 54-79 of TPN. The 24-hr urinary excretion of zinc was lower on days 54-79 than on days 1-5, but the rates of excretion of the other essential trace elements during TPN displayed no significant change. The urinary excretion of Cu, Fe, and Mn was numerically lower than the intravenous administration of these elements during days 1-5 and 54-79 of TPN, whereas the urinary excretion of zinc was lower than the supply only during days 54-79. The whole-blood concentration of zinc was low but constant during TPN, whereas the initially low levels of Cr and Fe were normalized on days 54-79. The results suggest that the supply of the essential trace elements Cr, Co, Cu, Fe, Mn, and Zn was largely adequate during two to three months of TPN and that the human body may adapt to a somewhat low supply of zinc, 20-30 mumol/24 hr.

Intracellular potassium in man. A comparison of in vivo and in vitro measurement techniques.

In order to evaluate different methods of estimating intracellular content of potassium, determinations of potassium were made in erythrocytes, in muscle biopsy specimens and in the total body. The total body potassium (TBK) was related to body weight (Bwt), lean body mass (LBM), dry LBM, soft fat-free solids (SFFS), total body water (TBW) and calculated intracellular fluid (ICF). Sixty-two healthy subjects and 80 patients with various diseases and therapy known to influence the potassium metabolism were studied. Statistically significant correlations were found between potassium content in muscle biopsies related to fat-free solids and TBK/Bwt (r = +0.56, P less than 0.05), TBK/LBM (r = + 0.58, P less than 0.01), dry LBM (r = + 0.54, P less than 0.05) and TBK/SFFS (r = + 0.68, P less than 0.01). A correlation was found between muscle potassium related to intramuscular water and TBK/TBW (r = + 0.47, P less than 0.05). No correlations were found between EK and TBK/LBM, TBK/dry LBM or TBK/ICF. Between EK and serum potassium a negative correlation (r = -0.31, P less than 0.05) was found in a group of untreated hypertensives. It is concluded that the quotients of TBK (TBK/LBM, TBK/TBW and TBK/SFFS) might be used in the study of intracellular potassium--at least in the study of patient groups.

Effect of digoxin upon intracellular potassium in man.

The effect of digoxin upon intramuscular potassium was studied by use of whole body counting and biopsy technique. Twelve healthy subjects and twelve outpatients with mild cardiac insufficiency or atrial arrhythmia were digitalised. Before and after digitalization total body potassium (TBK) was measured. Potassium concentration in muscle specimens (MK) was analysed by the neutron activation technique. Digoxin was measured in serum and in skeletal muscle tissue by radioimmunoassay, and QS2-index as a measure of the electromechanical systole. In both groups a significant decrease in TBK (P less than 0.05) and MK (P less than 0.01) was demonstrated in connection to digitalization. There was no correlation between the decrease in TBK and MK, or between the concentrations of digoxin in serum or muscle and the decrease in potassium concentration. The digoxin in serum in healthy subjects was 0.9 +/- 0.33 nmol/l and in patients 1.2 +/- 0.41 nmol/l. The digoxin in muscle was 39 +/- 10.9 nmol/kg dry weight in seven of the healthy individuals and 37 +/- 9.5 nmol/kg dry weight in nine patients. After digitalization a decrease of QS2-index was found in both groups (P less than 0.01).

Erythrocyte and total body potassium in untreated primary hypertension.

In a study of total body and erythrocyte potassium in mild hypertension we found decreased intracellular potassium concentrations in 41 hypertensives compared to controls but no correlation between intracellular potassium, measured by whole body counting, and erythrocyte potassium. A total body potassium corresponding to an intracellular potassium of 85% or less of the expected value was found in females. In the hypertensives, a negative correlation existed between serum and erythrocyte potassium. No correlation was found between potassium decrease and urinary aldosterone or plasma renin level. An inhibition of the active sodium-potassium exchange at the cellular level is proposed as an explanation of these findings.

Iron status in athletes involved in intense physical activity.

Iron status was studied in 8 long distance runners. Training programs, diets, and general health were also investigated over a period of at least 2 years. Hemoglobin and serum iron did not differ from normals whereas bone marrow showed either an absence or only traces of iron indicating latent iron deficiency. Radio iron studies of heme and non-heme iron absorption and incorporation showed rather low values. However, they did not differ significantly from normal values. Whole body counting studies during 10 months showed increased elimination of radio iron corresponding to 2 mg iron/day. Due to a high daily iron intake, a balance was present. No signs of bleeding, hemolysis, or increased excretion of hemoglobin via the urine could be found. The low aborption and increased elimination of iron seems to be the explanation for the empty iron stores.

Electrolytes and whole body potassium in acute leukemia.

In a consecutive series of 22 patients with acute leukemia, the total body potassium was studied in 18 patients on 39 occasions during relapse and remission. Total body water was also determined. A control group consisting of 88 age-matched healthy volunteers was also studied. The patients had a significantly lower mean potassium concentration, per kg body weight, per kg lean body mass and per kg water, than the controls (p less than 0.001). Individually, 11 out of the 18 patients had at least one value below the lower 95% confidence limit. Hypokalemia was frequent both in the patients with low (7/11) and normal (3/6) potassium per kg lean body mass. Five of 13 investigated patients showed laboratory indications of secondary hyperaldosteronism, which might be partly responsible for the hypokalemia. Increased serum or urine levels of lysozyme were found in 62% of the patients.

Staging of myeloma. A preliminary study of staging factors and treatment in different stages.

Attempts were made to find prognostic factors in myeloma. In 16 deceased patients, urinary light chains, skeletal lesions, and the quantity of the monoclonal protein fraction in the serum were correlated to prognosis, in contrast to the electrophoretic mobility of the monoclonal fraction, the hemoglobin, the serum creatinine value, the serum calcium, or the intestinal calcium absorption. Skeletal calcium uptake was only numerically higher in mild myeloma than in advanced myeloma. Since these findings partially agreed with the staging procedure previously proposed by Salmon, a modification of this procedure was used to stage 50 myeloma patients. Survival was statistically significantly shorter in stage III than in stage I. A differentiated treatement with melphalan-prednisone in stage I, cytoxan infusions in stage II, and vincristine-cytoxan-prednisone in stage III is proposed. A preliminary comparison of nine patients in stage II-III given intensive treatment with 23 given melphalan-prednisone suggests a numerically, but not as yet a statistically significant increase in survival in the intensively treated group, which seems to have an 80% 2-year survival.

Total body potassium measurements in 230 patients. A study of potassium depletion.

Three groups of patients with suspected potassium depletion were studied. Twenty-nine obese patients were observed before and up to 1 year after an intestinal shunt operation. During the first week after operation they lost almost 3 grams of potassium per day. The percentage potassium loss was much larger than the percentage weight loss. A significant decrease of serum potassium was also noted during the first week after operation. In contrast to the total body potassium, however, the serum potassium remained within normal limits in all patients except two. Fourteen patients subjected to a cardiac operation also showed a significant decrease of total body potassium concentration 1 week after operation. The serum potassium remained within normal limits. In 187 patients with suspected potassium depletion the total body potassium had been measured, and the results were examined retrospectively. In 38 of these patients the measured total body potassium was outside a 94% confidence interval for an individually predicted value, even though 26 of these 38 patients were taking oral potassium chloride tablets. In 23 of these 38 patients two or three risk factors - hypoalbumin-emia, treatment with diuretics, and treatment with digitalis - were present simultaneously, and in 10 patients one factor was present. Only 8 of the 38 patients had a low serum potassium value. It may therefore be concluded that the total body potassium measurement, when compared with an individually predicted value, seems to be more sensitive in estimation of potassium depletion than the commonly used serum potassium method.

Iron metabolism in porphyria cutanea tarda.

The iron metabolism has been studied in 11 patients with porphyria cutanea tarda. Despite significantly increased amounts of iron in the serum and liver, the porphyria patients absorb not less but significantly more radioiron than normal controls. Whereas phlebotomy-induced iron deficiency stimulates the absorption in controls, no further stimulation is found in the porphyria patients. The plasma iron turnover is high in the porphyria patients, and some of this iron is probably deposited in the liver. The relationship between the high iron absorption, high plasma iron turnover, high liver iron, liver damage and uroporphyrin production in the liver is discussed. It is suggested that two concurrent genetic defects may cause porphyria cutanea tarda, one in iron absorption and one in porphyrin synthesis by damaged liver cells. The absorption of inorganic iron was higher than that of hemaglobin iron. The possible damage which fortification with inorganic iron could cause to the very small group of porphyria patients is discussed.

Alterations in erythropoiesis preceding leukemia.

An attempt was made to study preleukemic changes in bone marrow cell proliferation. Seven patients with hypercellular marrows and aregenerative anemia were studied. Five of them could be followed to autopsy, several years after the kinetic studies; all died with a picture of leukemia. Total bone marrow cell numbers, erythroblast generation times, and erythrocyte production were estimated with 59Fe. Despite hypercellularity, the total erythroblast number was not significantly increased. Erythrocyte production and life span were both decreased, and erythroblast generation time were significantly longer than normal.