Serum aluminium and cobalt levels after ceramic-on-ceramic and metal-on-metal total hip replacement.

In a randomised study, 28 patients with a mean age of 62.2 years (32 to 81) with osteoarthritis or avascular necrosis of the hip received either a ceramic-on-ceramic or a metal-on-metal total hip replacement. Apart from the liners the acetabular and femoral components were made of Ti-Al-Nb alloy. The serum aluminium and cobalt levels were measured before, and at one year after surgery. The 15 patients in the ceramic-on-ceramic group had a median pre-operative aluminium level of 1.3 microg/l (0.25 to 8.4) and a cobalt level below the detection limit. At one year the aluminium level was 1.1 microg/l (0.25 to 2.3) and the cobalt level was 0.4 microg/l (0.15 to 0.7). The 13 patients in the metal-on-metal group had a median pre-operative aluminium level of 1.9 microg/l (0.25 to 4.4) and a cobalt level below the detection limit. At one year the median aluminium level was 0.9 microg/l (0.25 to 3.9) whereas the cobalt level was 1.4 microg/l (0.5 to 10.5). This increase in the cobalt level at one year was significant (p < 0.001). Our findings indicate that ceramic-on-ceramic bearings do not cause elevated levels of serum aluminium in the first post-operative year.

[Serum cobalt and serum chromium level in 2 patients with chronic renal failure after total hip prosthesis implantation with metal-metal gliding contact]. / Serumcobalt- und Serumchromspiegel bei zwei chronisch niereninsuffizienten Patientinnen mit Hüfttotalendoprothese und Metall-Metall-Gleitpaarung.

PURPOSE: The influence of chronic renal failure on serum cobalt and serum chromium in two patients with metal-on-metal bearing (Metasul) and cementless total hip arthroplasty (Alloclassic) is investigated. METHODS: Serum cobalt and serum chronium levels were determined in the postoperative course using atomic absorption spectrometry. RESULTS: Maximum values are found to be more than 100-fold elevated when compared to the reported median serum cobalt concentrations in patients with the same prosthesis type and no known renal disease. CONCLUSION: Chronic renal failure seems to be responsible for the marked elevation of serum cobalt and serum chromium. CLINICAL RELEVANCE: Despite evidence of adverse health reactions, a possible effect of long-term cobalt and chromium loading cannot be neglected. In our opinion, metal-on-metal bearings in THA should not be inserted in patients with chronic renal failure. Follow-up investigations (serum cobalt, serum chromium, serum creatinine, BUN, echocardiography) should be performed at short intervals.

Elevated serum cobalt with metal-on-metal articulating surfaces.

We determined serum cobalt levels in 55 patients by atomic absorption spectrophotometry before and after implantation of uncemented total hip arthroplasties. In a randomised, prospective trial 27 wrought Co-28Cr-6Mo-0.2C metal-on-metal articulations were compared with 28 ceramic-on-polyethylene hips which did not contain cobalt. Other sources of iatrogenic cobalt loading were excluded. The metal-on-metal group produced detectable serum cobalt levels (median 1.1 microg/l after one year) which were significantly different (p < 0.0001) from those of the ceramic-on-polyethylene control group (median below detection limit of 0.3 microg/l after one year). Our findings indicate that metal-on-metal bearings generate some systemic release of cobalt.

Oral zinc and the second eye in age-related macular degeneration.

PURPOSE: To investigate the short-term effect of oral zinc substitution on the development of age-related macular degeneration in the second eye of patients with an exudative form of the disease in the first eye. METHODS: A 2-year, double-masked, randomized, placebo-controlled study including 112 white patients with age-related macular degeneration and exudative lesions (choroidal neovascularization, pigment epithelial detachment, or both) in one eye and a visual acuity of better than 20/40 and macular degeneration without any exudative lesion in the second eye was performed. Patients received either 200 mg of oral zinc sulfate or placebo once daily for 24 months. The main outcome parameters were visual acuity, contrast sensitivity, color discrimination, and retinal grating acuity, as well as serum levels of zinc and copper, red blood cell count, hemoglobin, and morphologic changes detected by grading of monochrome fundus photographs and fluorescein angiograms. RESULTS: In the treatment group, the mean zinc serum level increased significantly (P < 0.0001) from 79 +/- 10 micrograms/dl to 108 +/- 26 micrograms/dl compared to no change (82 +/- 16 micrograms/dl to 85 +/- 10 micrograms/dl) in the placebo group. Serum levels of copper, hemoglobin, and red blood cell count did not change significantly in either group. A choroidal neovascular membrane (CNV) was detected in 14 patients during the treatment period (nine in the treatment group, five in the placebo group). Seven additional patients (three in the treatment group, four in the placebo group) experienced visual loss caused by CNV, and in two patients (one in each group), serous pigment epithelial detachment developed without angiographic evidence of CNV after the end of treatment, during a mean additional follow-up time of 20.8 +/- 8.2 months. In eyes in which exudative lesions did not develop, there was no significant change in any of the functional parameters during the 24-month treatment period, but there was a significant increase in the nonexudative alterations (drusen size, drusen confluence, hyperpigmentation, and focal degeneration of the retinal pigment epithelium) in both groups. CONCLUSIONS: Oral zinc substitution has no short-term effect on the course of age-related macular degeneration in patients who have an exudative form of the disease in one eye.

Measurement of extracellular fluid carboplatin kinetics in melanoma metastases with microdialysis.

Clinical anti-tumour efficacy of anti-cancer drugs is a function of dose intensity, i.e. the concentration--time profile in tumour tissue. Hence, information on drug concentration profiles in tumours is of critical importance but appropriate methods for measurement are lacking. The aim of the present study was to obtain, by microdialysis sampling, concentration--time profiles in a solid tumour (melanoma) of a model anti-cancer drug, carboplatin, and thereby to assess the scope of microdialysis for tumour pharmacokinetic studies in man. Six patients with cutaneous melanoma metastases at the extremities or body trunk, scheduled to receive carboplatin (400 mg m-2 i.v.) were studied. Carboplatin concentrations were monitored in serum, intratumoral and subcutaneous tissue. Calibration of the microdialysis probes was carried out in vitro and in vivo with use of the retrodialysis method. Complete carboplatin concentration vs time profiles in tumour and subcutaneous tissue were obtained. Major pharmacokinetic parameters (maximum concentration, time to maximum concentration, area under the curve, elimination half-life) were calculated for tissues and tumour/serum concentration ratios for carboplatin were derived. Mean free concentrations of carboplatin in cutaneous melanoma metastases reached only about 50-60% of total serum levels; maximal intratumoral concentrations were 7.6 (+/-2.0; s.e.m.) microgram/ml, mean concentrations in subcutaneous tissue were similar to those in tumour. The present study demonstrates that microdialysis is a novel tool for measuring drug concentrations in solid tumours in humans in vivo and appears to be a valuable addition for pharmacokinetic/pharmacodynamic studies in oncology.

Effect of lead on blood pressure in occupationally nonexposed men.

To determine if low-level exposure to lead has an effect on arterial blood pressure, demographic and clinical data of a group of 507 males without any occupational exposure to lead were analyzed in a retrospective study. The following variables were included in the analysis: age, height, weight, nicotine consumption, alcohol intake, blood lead, systolic blood pressure, diastolic blood pressure, and erythrocyte count. The effects of the variables age, weight, height, alcohol intake, nicotine consumption, and blood lead on blood pressure were investigated by stepwise linear regression analysis. The diastolic as well as the systolic blood pressure was significantly influenced by Body Mass Index, age, and alcohol. A significant effect of lead could be found only for diastolic blood pressure. None of the possible interactions were significant enough to merit inclusion in the statistical model. Regarding the strength of the effects on diastolic blood pressure we find that lead ranks after age, weight. In conclusion, this study shows that lead has an effect on diastolic arterial blood pressure in a survey of a group of middle-aged, occupationally nonexposed men.

Zinc levels of serum and cervicovaginal secretion in recurrent vulvovaginal candidiasis.

OBJECTIVE: To determine whether zinc deficiency in serum or vulvovaginal secretion is a risk factor for recurrent vulvovaginal candidiasis. DESIGN: Prospective and controlled study. SETTING: Department of Dermatology, University of Vienna. SUBJECTS: 21 women who had experienced at least three documented episodes of acute vulvovaginal candidiasis within the previous 12 months. Fifteen women without anamnesis of vulvovaginal candidiasis as a control group. INTERVENTIONS: Blood samples were drawn for measurement of plasma zinc levels. Lavage of the vagina and ectocervix was performed with sterile saline solution for measurement of cervicovaginal zinc levels. MAIN OUTCOME MEASURES: Zinc levels of serum and cervicovaginal secretions were determined by flame atomic absorption spectrophotometry. RESULTS: We found no significant difference in the mean zinc concentration of plasma and cervicovaginal secretions between the recurrent vulvovaginal candidiasis and the control group. (p value for serum = 0.71, p value for secretion = 0.80). Zinc levels of plasma and cervicovaginal secretions showed no correlation (patient group: r = -0.05, control group: r = -0.07). CONCLUSION: It is well known that zinc not only exerts a major impact on different immune functions, but also participates in growth and morphogenesis of Candida albicans. Our results could not confirm the previous hypothesis that zinc deficiency of serum is a risk factor in recurrent vulvovaginal candidiasis. It is possible that the local zinc level of cervicovaginal secretions essentially influences antifungal activity of third generation azole antimycotics.

[Lead, mercury and cadmium in newborn infants and their mothers]. / Blei, Quecksilber und Cadmium bei Neugeborenen und deren Müttern.

The objective of the present study was to determine the toxic trace element status of 51 healthy Austrian women and their newborn babies. Lead, mercury and cadmium content of early breast milk, blood and urine were measured post partum by atomic absorption spectrophotometry. None of the toxic trace elements could be found in elevated concentrations; the content of mercury and cadmium in milk was below limits of detection. Mean lead concentration in breast milk was 35.8 (SD:15.0) micrograms/l. Whole blood content of lead was 37.0 (SD:12.7) micrograms/l in mothers and 26.3 (SD:11.6) in newborns. High blood concentrations of mercury were found both in mothers (4.46 micrograms/l, SD:1.95) and in umbilical cord blood (5.58 micrograms/l, SD:2.33). The corresponding values for cadmium were 0.44 (SD:0.4) micrograms/l and 0.08 (SD:0.16) micrograms/l. Urine excretion of the elements assayed was normal. Significant correlations between maternal and neonatal blood toxic mineral levels could be demonstrated in lead (p < 0.001).

[Neurologic symptoms in inhalation poisoning with metallic mercury]. / Neurologische Symptome bei Inhalationsvergiftung mit metallischem Quecksilber.

Nineteen caisson workers had been exposed to metallic mercury vapours while digging tubes underneath the first district of Vienna (exposure between 470 and 2440 min; mean 1621 min). The blood mercury values on admission were between 29 and 166 micrograms/l (mean 75 +/- 34 micrograms/l). The main findings reported are clinical neurologic symptoms, psychic complaints, neurographic results and autonomic parameters (cardiovascular reflexes): 47% complained of headache and tiredness, 37% showed tremor and suffered from sleep disturbances, 26% showed hypersalivation, 16% changes in handwriting, and 11% slight dysarthria. The cardiovascular reflexes (autonomic parameters) were abnormal in 7 of 12 patients. On neurography the distal latency (median nerve) was pathologic in 47%, the distal latency (peroneal nerve) was pathologic in 26%, the antidromic sensory nerve conduction velocity (median nerve) was abnormal in 10%, the motor nerve conduction velocity, compound amplitude and vibratory threshold were normal.

Spontaneous and interferon-induced natural cytotoxicity in Crohn's disease.

Natural killer cell (NK) activity and antibody-dependent cellular cytotoxicity (ADCC) exerted by peripheral blood mononuclear cells (PMNC) were investigated in 53 patients with Crohn's disease (CD). NK activity and ADCC were found to be significantly reduced in patients with CD (p less than 0.0005) as compared to healthy controls. Both effector cell functions increased after in vitro treatment of PMNC with gamma-interferon, but did not reach the levels found in controls (p less than 0.0005). Neither NK activity nor ADCC was significantly influenced by therapy with corticosteroids. Moreover, the reduced serum zinc levels in patients with CD, which have been shown to be associated with impaired immune function, did not influence the lytic effector cell mechanism assayed either. Finally, no association could be found between NK cell activity or ADCC and CD activity index, the extent of the disease and several laboratory parameters of inflammation. We conclude that patients with CD have a reduced lytic effector cell function which remains uninfluenced by corticosteroid treatment and seems to be present independently of disease activity.

[Heavy metal and trace element deviations. A comparison of idiopathic dilated cardiomyopathy and coronary heart disease]. / Schwermetall- und Spurenelementdeviationen. Eine Gegenüberstellung von idiopathischer dilatativer Kardiomyopathie und koronarer Herzkrankheit.

Blood, serum and urine (24-hour-samples) concentrations of cadmium, zinc, calcium and magnesium were determined by means of atomic absorption spectrophotometry in 60 patients, therefrom 30 patients with idiopathic dilated cardiomyopathy (IDC) and 30 patients with coronary heart disease (CHD). The data of heavy metal and trace element concentrations of IDC and CHD patients were compared with each other and furthermore, for each group separately, correlated with patients history data, laboratory evaluations and data from heart catherization protocol. IDC patients showed higher blood cadmium concentrations (p less than 0.001) and lower serum zinc concentrations (p less than 0.001) compared to CHD patients. Serum levels of calcium and magnesium were not different in both groups. In urine samples IDC patients had lower concentrations of calcium (p less than 0.01) and magnesium (p less than 0.01) compared to CHD patients. Urine concentrations of cadmium and zinc were in the same range in both groups. The comparison of heavy metal and trace element concentrations with clinical data did not reveal definite correlations, however, data from experimental studies pointing out interactions of heavy metals and trace elements, could serve as useful interpretations. Hypomagnesemia in both patient groups (IDC, CHD) requires clinical follow up and substitution treatment.

Iron removal by desferrioxamine in patients on chronic hemodialysis--kinetic study and long-term results.

Serum ferritin levels, cumulative number of administered blood transfusions, number of monthly transfused blood units and total months on hemodialysis (HD) treatment differed significantly in 7 patients on hemodialysis with clinical, biochemical and histological evidence of hemosiderosis, when compared to 37 controls (p less than 0.001 for all parameters). As a new treatment method desferrioxamine (DFO) therapy was introduced for iron detoxification in these hemosiderotic chronically hemodialyzed patients. Hence, to maximize the biological half-time, 30 mg/kg body weight DFO were given after the end of HD in the iron-loaded patients. Iron removal during the subsequent HD and the increase of iron excretion by the stool after DFO was measured by atomic absorption spectroscopy. Iron removal by the artificial kidney was calculated by investigating the function (QDi + QF)CDo over the duration of HD treatment, which equals the total amount of iron removal during HD. Using numerical integration of measured data this removal was found to be 21.8 +/- 6.9 mg whereas cumulative iron loss via the feces was found to be 36.5 +/- 14.6 mg. Therefore, total iron elimination was calculated to be on average 50-60 mg after administration of a single dose of DFO. Furthermore, long-term treatment of 5 patients resulted in a significant decrease of serum ferritin levels from 2,309 +/- 295 to 715 +/- 177 ng WHO/ml (p less than 0.001) after a period of 36 +/- 5 months. We conclude, that DFO in a dosage of 30 mg/kg body weight given at the end of HD is able to remove more than 500 mg iron/month if it is administered following each HD. Long-term results indicate negative iron balance without significant change of transfusion frequency if not more than 2 U of blood (500 mg iron) are administered within 1 month. This treatment schedule might be superior compared to the previously used methods of administration where DFO was given at the beginning or throughout HD.

Effect of desferrioxamine on aluminum kinetics during hemodialysis.

The effects of desferrioxamine administration on aluminum kinetics during hemodialysis were studied. Desferrioxamine leads to an increase of plasma aluminum levels in patients on chronic hemodialysis which could be attributed to mobilization of tissue aluminum. The in vivo protein binding of aluminum was found to be 70% after administration of desferrioxamine vs. 80% without a premedication with desferrioxamine, thus greatly enhancing the concentration gradient between free diffusible plasma aluminum and dialysate aluminum. Desferrioxamine therefore leads to increased aluminum removal during hemodialysis and should be considered in the therapy of aluminum toxicity syndromes.

Aluminum removal by hemodialysis.

Aluminum kinetics were studied in 24 patients on chronic hemodialysis. All patients had elevated predialytic serum concentrations of aluminum (mean, 3.44 mumoles/liter), which correlated significantly with the ingestion of aluminum hydroxide (P less than 0.01). Simultaneous measurements of aluminum in plasma and ultrafiltrate revealed an ultrafiltrability of about 20% of total plasma aluminum, thus suggesting that 80% of aluminum is protein bound. When a dialysate with a very low aluminum content (varying from 0.1 to 0.3 mumoles/liter) was used, mean values across the dialyzer were 3.20 and 2.67 mumoles/liter, respectively, showing a significant decrease of plasma aluminum during dialyzer passage (P less than 0.0001). It could be shown that dialysance of aluminum depends on the concentration gradient between the free diffusible plasma aluminum and the dialysate aluminum concentration. After 6 hours of dialysis, plasma aluminum concentrations were significantly lower than were predialysis values (P less than 0.0001). We conclude that a negative aluminum balance during hemodialysis can be assumed as long as the aluminum concentration of free diffusible plasma aluminum lies above the aluminum concentration of the dialysate.