Specific IgG to Thermoactynomices vulgaris, Micropolyspora faeni and Aspergillus fumigatus in building workers exposed to esparto grass (plasterers) and in patients with esparto-induced hypersensitivity pneumonitis.

BACKGROUND: Esparto is one the most frequent causes of hypersensitivity pneumonitis in Spain. OBJECTIVE: Determination of risk factors in the working environment that could explain the sensitisation process, and assessment of the differences in specific IgG levels to Aspergillus fumigatus, Saccharopolyspora rectivirgula and Thermoactynomices vulgaris in patients with hypersensitivity pneumonitis induced by esparto, exposed healthy plasterers and control population. METHODS: Determination of precipitins and specific IgG to Aspergillusfumigatus, Saccharopolyspora rectivirgula and Thermoactynomices vulgaris in the three previously mentioned groups. Questionnaire on possible risk occupational and extra-occupational factors. RESULTS: Both healthy and exposed plasterers have higher levels of specific IgG to Aspergillus fumigatus, Saccharopolyspora rectivirgula and Thermoactynomices vulgaris than the healthy controls. The patients had higher levels of IgG than exposed healthy plasterers only to Thermoactynomices vulgaris. Precipitins were detected in only two patients. There were no occupational factors influencing on the sensitisation process. CONCLUSIONS: Specific IgG is an occupational exposure marker among plasterers, but it has not been possible to establish a cut off point that differentiates exposed subjects from affected ones. This determination has a greater sensitivity than precipitins. We did not identify occupational or extra-occupational risk factors that facilitate the sensitisation process.

Different patterns of renal osteodystrophy in Iberoamerica.

The various forms of renal osteodystrophy are predominant hyperparathyroid bone disease, mixed uremic osteodystrophy, low turnover osteomalacia, and adynamic bone disease. The present study analyses a total number of 1,209 bone biopsies from 5 different countries (Brazil, Uruguay, Argentina, Portugal, and Spain). Low turnover osteomalacia and mixed uremic osteodystrophy were more common in Brazil, Uruguay, and Argentina than in Portugal and Spain whereas predominant hyperparathyroid bone disease was seen more often in Portugal and Spain. In all centers, independent of the aluminum staining technique used, the extent of aluminum deposited in bone was greater in patients presenting with low bone turnover, whether from low turnover osteomalacia or adynamic bone disease, than in the predominant hyperparathyroid bone disease. In summary, even though recent reports have indicated that, over the last decade, the incidence of aluminum-induced toxicity was reduced, aluminum still seems to be implicated in a great percentage of symptomatic low bone remodelling lesions in Iberoamerica.

The role of imaging techniques in the study of renal osteodystrophy.

Secondary hyperparathyroidism is the most common form of this condition found in renal osteodystrophy. Enlarged parathyroid glands are the rule in severe secondary hyperparathyroidism because of a marked parathyroid cell hyperplasia. For several years, ultrasonography, computed tomography, and scintigraphy with thallium201-technetium99 have been useful techniques to identify enlarged parathyroid glands. More recently, ultrasonography with color Doppler and parathyroid scintigraphy with 99mTc-sestamibi have proved to be useful as well. Computed tomography and magnetic resonance imaging can be used, but their sensitivity is similar to ultrasonography and they cost more. Ultrasonography with color Doppler signals has made it possible to evaluate tissue blood supply, an aid in differentiating thyroid nodules. The degree of blood supply may be an indirect index of cell proliferation when there is neither necrosis nor calcification, because an enriched blood supply suggests vigorous cell growth and nodule formation. Scintigraphy with 99mTc-sestamibi allows identification of ectopic glands, including those located in the mediastinum, and also provides functional information. Sestamibi uptake is closely related to both parathyroid hormone levels and to the histological type of parathyroid proliferation. In our experience, when hyperparathyroidism is not too severe, 2 weeks after 2 g of calcitriol is administered intravenously, these scintigraphic images can disappear (inhibition test). This suggests a possibility for a medical treatment. By contrast, when parathyroid hormone levels are higher, parathyroid sestamibi uptake remained unchanged. In such patients, parathyroidectomy or ethanol injection should be the best treatment. These glands would correspond to the most actively functioning glands; they would have a lesser expression of vitamin D receptors, rendering them refractory to medical treatment with calcitriol.

Are there any differences in the parathyroid response in the different types of renal osteodystrophy?

With the purpose of studying the curve of parathyroid response to variations of serum calcium during dialysis, we studied 20 patients on haemodialysis: 10 women and 10 men, with different forms of bone disease diagnosed by bone biopsy (adynamic bone disease, mild hyperparathyroidism, severe hyperparathyroidism). In all patients, we performed parathyroid stimulation by 4 h dialysis with 1 mEq/l of Ca2+ in the dialysate, and an inhibition test in another dialysis session with 4 mEq/l of Ca2+, with a 48 h interval. Ca2+ and intact parathyroid hormone (iPTH) were measured prior to dialysis and every hour subsequently, to obtain a Ca2+-iPTH for each patient. The analysis of the curves was made using Brown's four-parameter model. Stimulation and inhibition levels were similar in all groups, but basal iPTH and the response profiles obtained varied in the different histological groups. Basal, maximal and minimal iPTH were lower in adynamic forms than in the other two groups (P<0.04), and basal calcium was higher than basal calcium of severe hyperparathyroidism, expressing a basal inhibition status. In severe hyperparathyroidism, basal calcium was lower than the set-point, showing a permanent stimulation, and the slope was higher than in other groups, showing more sensitivity to serum calcium variations. The set-point of severe hyperparathyroidism was significantly higher than the set-point of mild and adynamic forms. In conclusion, the functional parathyroid study showed a different response in the different forms of renal osteodystrophy.

Serum aluminum transport and aluminum uptake in chronic renal failure: role of iron and aluminum metabolism.

Several factors have been blamed for increasing gastrointestinal absorption of aluminum. The likely role of iron metabolism was suggested some years ago. As iron and aluminum share many chemical properties, it is reasonable to think they also share biological pathways. The aim of this study was: (a) to evaluate serum aluminum transport and its relationship with iron-binding capacity, and (b) to investigate aluminum hydroxide absorption as a function of iron and aluminum. We investigated 127 patients with chronic renal failure undergoing hemodialysis in a study divided into two phases: phase 1, a basal study to investigate serum iron and aluminum status, and phase 2 in which an aluminum absorption test was performed. In phase 1, we found that the lower basal serum iron and iron transferrin saturation the greater serum aluminum (p < 0.001). In phase 2, we found a negative relationship between serum aluminum increments after the test and basal levels of serum aluminum and iron (r = -0.70; p < 0.001). These results suggest that the amount of either aluminum or iron carried by transferrin may influence the transferrin capacity to bind the other element and also may modulate, together with other factors, the gastrointestinal absorption of iron and aluminum.

Influence of iron status in the response to the deferoxamine test.

The study presented here was carried out to evaluate the possible relationship between serum iron and iron transferrin saturation with the response to the deferoxamine test in 86 chronic renal failure patients undergoing hemodialysis. The deferoxamine test was performed as a diagnostic tool for aluminum intoxication. Basal serum aluminum levels correlated with: (1) serum aluminum levels after the infusion of deferoxamine (r = 0.45; P < 0.05); (2) serum iron levels (r = -0.26; P < 0.05), and; (3) iron transferrin saturation (r = -0.33; P < 0.05). The increase in serum aluminum levels after deferoxamine administration (DAI) showed a negative relationship with serum iron levels (r = -0.23; P < 0.05) and iron transferrin saturation (r = -0.26; P < 0.05). The correlations improved when analysis of this study included only those patients with high serum iron levels or high iron transferrin saturation (r = -0.55). Patients with low probability of having aluminum overload (serum iron levels < 40 micrograms/L and DAI < 150 micrograms/L) had significantly higher values of serum iron, iron transferrin saturation, and serum ferritin levels compared with those patients with a high probability of having aluminum overload (serum aluminum levels > 40 micrograms/L and DAI > 150 micrograms/L). The study presented here suggests that patients who have indicators of iron repletion would tend to have lower increases in serum aluminum levels after the challenge with deferoxamine and presumably a higher incidence of false negative results with the deferoxamine test. These findings indicate that iron measurements must be always taken into account when interpreting the deferoxamine test.

[(99m)Tc]-sestamibi parathyroid scintigraphy in chronic haemodialysis patients: static and dynamic explorations.

BACKGROUND: The place of parathyroid gland imaging by [(99m)Tc](technetium)-sestamibi scintigraphy in uraemic patients with secondary hyperparathyroidism remains a matter of debate. The purpose of the present study was (i) to assess its value with respect to plasma intact parathyroid hormone (iPTH) levels and to surgical parathyroidectomy (PTx), and (ii) to explore the possibility of suppressing parathyroid [(99m)Tc]-sestamibi uptake by calcitriol. METHODS: In a first cross-sectional, static study 52 chronic haemodialysis (HD) patients with plasma iPTH levels between 14 and 2791 pg/ml (normal, 10-65 pg/ml) had a [(99m)Tc]-sestamibi scan, and 21 of them underwent surgical PTx. In a second longitudinal, dynamic study 14 chronic HD patients with advanced secondary hyperparathyroidism received short-term calcitriol treatment in an attempt to suppress [(99m)Tc]-sestamibi imaging of parathyroid glands. Calcitriol was given intravenously for 2 weeks, 2 microg after each haemodialysis session. Scintigraphy was carried out before and at the end of this inhibition test. RESULTS: [(99m)Tc]-Sestamibi scan led to imaging of one or more (maximum three) parathyroid glands in most, but not all, HD patients with plasma iPTH values >600 pg/ml. Based on surgical findings, overall sensitivity of [(99m)Tc]-sestamibi scan in correctly locating parathyroid glands was only 50%, whereas specificity was 100%. In contrast, its sensitivity was 100% in locating single glands in the subgroup of five patients with recurrent hyperparathyroidism. The calcitriol inhibition test showed suppression of [(99m)Tc]-sestamibi uptake by at least one parathyroid gland in eight patients (57%), with complete suppression in five of them (36%). Basal plasma iPTH or decrease of plasma iPTH in response to calcitriol was not predictive of suppressible [(99m)Tc]-sestamibi uptake in the individual case, although mean iPTH was markedly higher in patients with non-suppressible parathyroid glands. CONCLUSION: Because of its relatively low sensitivity the [(99m)Tc]-sestamibi scan is of limited help in the exploration of uraemic patients with severe secondary hyperparathyroidism before a first surgical PTx. However, it is very useful in locating the remaining parathyroid gland(s) in case of reoperation. The novel calcitriol inhibition test of [(99m)Tc]-sestamibi uptake could help to better distinguish parathyroid glands with non-suppressible, autonomous activity from glands whose activity might be amenable to long-term suppression.

Can we use 99mTc-MIBI in functional studies of the parathyroid gland?

The usefulness of technetium-99m-sestamibi (99mTc-MIBI) in patients with secondary hyperparathyroidism on haemodialysis was assessed. We studied 33 patients with parathyroid scintigraphy with i.v. (99mTc-MIBI). Static images in a scintillation camera were taken at 15 and 120 min after the injection. With P x Ca<80, we performed an inhibition test with calcitriol i.v. 2 microg, three times a week, for 2 weeks. The MIBI study and assessment of intact parathyroid hormone (iPTH) were performed before (baseline study) and after inhibition. A 'focal positive study' corresponded to one or more areas of abnormal hypercaptation in relation to surrounding thyroid tissue seen in early images and persisting in later images, and a 'negative study' did not correspond to the previous image. In the baseline study, iPTH in the positive MIBI group was significantly greater than in the negative group. Eight positive MIBI patients had a bone biopsy; six corresponded to severe osteitis fibrosa and two to mild osteitis fibrosa. In the negative MIBI group, four of the six patients who had bone biopsy had mild forms of osteitis fibrosa (Fisher=0.03); the other two had low turnover forms. A positive inhibition test was defined when the basal uptake disappeared after calcitriol administration. In these patients, we observed a significant decrease of iPTH, not observed in the negative inhibition test. In 10 patients who had been parathyroidectomized, those with alpha positive basal MIBI result had a nodular parathyroid hyperplasia. We conclude that a scintigraphic parathyroid study with 99mTc-MIBI showed a good correlation with functional parathyroid status. With the same inhibition test, only some glands were inhibited, suggesting that this could be the expression of different vitamin D receptor densities in inhibited glands and/or a different kind of proliferation in those glands. This test would be of value in functional studies when a therapeutic decision must be made.