[Basopil Activation Test (BAT) as a novel method for monitoring occupational exposure to Beta-lactams and intermediates of production]. / Utilizzo del test di attivazione dei basofili (BAT) nella sorveglianza sanitaria di lavoratori esposti a Beta--lattamici e ad intermedi di produzione.

BACKGROUND: Cutaneous tests and specific IgE are used in the diagnosis of allergy due to beta-lactans, although drug administration at therapeutic dosage is considered gold standard in drug allergy. OBJECTIVES: The diagnostic approach in symptomatic workers is more critical when they are exposed because of work, unlike reactions to drug in case of therapy. There is not a general consensus about markers in workers occupationally exposed to drugs. Indeed, basophil activation test (BAT) is a new and promising laboratory tool, particularly useful to test intermediate molecules involved in the production. In this article we show our experience on the health surveillance of workers exposed to beta lactams and intermediate molecule (7-ZACA) in a pharmaceutical industry. METHODS: We studied 15 workers divided into 3 groups: 5 exposed and symptomatic (group A), 5 exposed and asymptomatic (group B), 5 non exposed and asymptomatic (group C). RESULTS: BAT was positive for 7-ZACA in three subjects of group A, and in one subject of group B and one of group C. There was e concordance between clinical history, respiratory symptoms, and results of texts. It was possible to determine allergic nature of symptoms and sensitization in a preclinical phase, correctly discriminating symptoms related to irritants from the allergic ones. CONCLUSIONS: BAT, a simple and quick diagnostic procedure if compared to challenge, can be used as a useful and practical tool by occupational doctors for prevention measures, evaluation of ability to a specific job and reallocation of workers.

Clinical impact of hypercalcemia in kidney transplant.

Hypercalcemia (HC) has been variably reported in kidney transplanted (KTx) recipients (5-15%). Calcium levels peak around the 3rd month after KTx and thereafter slightly reduce and stabilize. Though many factors have been claimed to induce HC after KTx, the persistence of posttransplant hyperparathyroidism (PT-HPT) of moderate-severe degree is universally considered the first causal factor. Though not proven, there are experimental and clinical suggestions that HC can adversely affect either the graft (nephrocalcinosis) and other organs or systems (vascular calcifications, erythrocytosis, pancreatitis, etc.). However, there is no conclusive evidence that correction of serum calcium levels might avoid the occurrence of these claimed clinical effects of HC. The best way to reduce the occurrence of HC after KTx is to treat as best we can the secondary hyperparathyroidism (SHP) during the uraemic stages. The indication to Parathyroidectomy (PTX), either before or after KTx, in order to prevent or to treat, respectively, HC after KTx, is still a matter of debate which has been revived by the availability of the calcimimetic cinacalcet for the treatment of PT-HPT. However, we still need to better clarify many points as regards the potential adverse effects related to either PTX or cinacalcet use in this clinical set, and we are waiting for the results of future randomized controlled trials to achieve some more definite conclusions on this topic.

Calcium and phosphate changes after renal transplantation.

Hypercalcemia and hypophosphatemia are frequently observed in recipients of a kidney transplant (KTx). Hypercalcemia has been reported in up to 66% of KTx patients. Many factors have been suggested as the putative causal factors; however, the persistence of moderate-severe secondary hyperparathyroidism, associated with a change in the set-point of the Ca-controlled parathyroid hormone (PTH) secretion, is considered to play a prominent role. Hypercalcemia can negatively impact on both the graft and patient outcome, increasing the incidence of nephrocalcinosis, which can induce a worse graft outcome, inducing vascular calcifications, and increasing the incidence of pancreatitis. In addition, severe hypercalcemia after KTx often requires parathyroidectomy, which is not universally considered a safe medical solution in this clinical setting. After KTx, phosphate levels often fall below the normal range, with hypophosphatemia being observed in up to 40% of patients. The putative causal factors for this metabolic alteration are persistent hyperparathyroidism, increased levels of FGF-23, tubular damage secondary to the immunological effects, and toxic and vascular effectors. Hypophosphatemia can negatively impact on either skeletal or muscular systems, contributing to the increased incidence of bone fractures in KTx patients. The current therapeutic options should take into account an accurate pretransplant treatment and screening of the waiting-list patient and should also evaluate the efficacy and safety profile of the new pharmacological tools (calcimimetics) in comparison with the classical surgical approach (parathyroidectomy).

[Clinical impact of hypercalcemia after kidney transplant]. / Impatto clinico dell'ipercalcemia nel trapianto renale.

Hypercalcemia is a relatively common finding after kidney transplant, and when correctly evaluated has been reported to be present in around 5-15% of patients. The peak of its incidence can be found after the third month from transplantation and it usually maintains relatively constant levels, even though a moderate attenuation of the phenomenon can be expected in the long term. Many factors have been claimed to cause hypercalcemia after kidney transplant. However, the main recognized factor is the degree of persistent hyperparathyroidism deriving from a long previous history of uremia. It has been suggested that hypercalcemia can be damaging to both graft (induction of nephrocalcinosis, reduction of graft survival) and other organ or system functions (vascular calcification, erythrocytosis, pancreatitis, etc.). However, there is no definitive demonstration of a cause-effect relationship between hypercalcemia and the above-mentioned clinical events. Furthermore, it is not possible to establish to what extent these effects are due to hypercalcemia per se or also to increased PTH levels, which are often associated with hypercalcemia. In addition, there is no definitive evidence that correction of hypercalcemia might solve the above-mentioned clinical events. The best way to reduce the incidence of hypercalcemia is considered to be the optimization of therapy for secondary hyperparathyroidism during the pretransplant period. It has long been thought that parathyroidectomy was the only way to solve the problem of stabilized hypercalcemia associated with moderate-severe persistent hyperparathyroidism after kidney transplant. The introduction of calcimimetics, which have substantially changed the therapeutic approach to secondary hyperparathyroidism in dialysis patients, seems to be promising also in this field. However, many issues need to be clarified before its definitive inclusion into the therapeutic armamentarium of the transplant patient who is already burdened by so many medications.