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Biomedical subjects

G Salvagno

Publications and source records attributed to G Salvagno.

6 recordsLinked to original sources

The acute-phase response after bisphosphonate administration.

In patients who have never previously received bisphosphonate therapy, the intravenous administration of 4-amino-1-hydroxybuthilidene-1,1-bisphosphonate (AHButBP), 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), or 6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) induced an acute-phase response (APR) irrespective of the underlying disease, manifested by a fall in circulating lymphocyte number and serum zinc concentration and in a rise in C-reactive protein (CRP); a febrile reaction occurred in 30% of the patients. The APR was maximally expressed within 28-36 hours of i.v. administration of the bisphosphonates and disappeared 2-3 days later despite continuous treatment. These effects were dose dependent and the lowest doses necessary for an APR were 10 mg of AHButBP and AHPrBP and 75 mg of AHHexBP. Doses up to 1,000 mg/day i.v. of dichloromethanebisphosphonate (Cl2MBP) were devoid of these side effects. In patients treated with either a single i.v. dose of amino-bisphosphonates which resulted in an APR or with a suboptimal dose, a subsequent challenge 12-160 days later of the high dose failed to cause a rise in CRP or a fall in the lymphocyte count. The desensitization to AHButBP or AHPrBP was also seen following pretreatment with Cl2MBP. These findings suggest that bisphosphonates interact with macrophage-like cells resident in the skeleton and stimulate interleukin-1 release which is responsible for the appearance of the APR. At the same time, however, the bisphosphonates render these cells insensitive to further stimulation for several months.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗

The use of dichloromethylene bisphosphonate and aminobutane bisphosphonate in hypercalcemia of malignancy.

54 patients with malignant hypercalcemia were treated with either dichloromethylene bisphosphonate (Cl2MBP) or aminobutane bisphosphonate (AHButBP). Both compounds infused intravenously (i.v.) were rapidly effective in lowering serum calcium to normal range and a potency ratio between Cl2MBP and AHButBP could be roughly estimated as 1:100-250. 600 mg of Cl2MBP infused in one day over 9 h in nine patients were only slightly less effective (serum calcium from 12.3 +/- 1.7 to 10.1 +/- 1.1 SE, mg/dl) than 3300 mg infused in 11 consecutive days (13.4 +/- 1.9 to 9.3 +/- 1.2 SE, mg/dl). Thus the effectiveness of treatment with Cl2MBP was related better to the overall time of infusion than to the cumulative dose administered. This could not be demonstrated in a similar trial using AHButBP. 1600 mg Cl2MBP daily p.o. was unable to prevent the relapse of hypercalcemia in four patients after a treatment course with i.v. bisphosphonates. 100 mg of Cl2MBP intramuscularly maintained serum calcium within the normal range in two out of eight patients; however, weekly infusions of either Cl2MBP or AHButBP prevented the relapse of hypercalcemia in eight similarly treated patients for several weeks. Providing that adequate dosages are adopted, parenteral Cl2MBP and AHButBP may be a useful measure for controlling hypercalcemia in patients with carcinoma.

Administration, Oral↗

Treatment of Paget's disease of bone with intravenous 4-amino-1-hydroxybutylidene-1,1-bisphosphonate.

4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHButBP) was given intravenously (2.5-25 mg/day for 4 days) to 14 patients with Paget's disease of bone, five of whom had been treated with dichloromethylidene bisphosphonate (C12MBP) 32 months earlier. In the nine patients who had not been treated previously with bisphosphonates, the short course of AHButBP induced a suppression of serum alkaline phosphatase and urinary hydroxyproline values down to 30% of initial values. The biochemical suppression of the disease was sustained for 2-18 months and the time to relapse did correlate to the logarithm of the dose (P less than 0.001). In the five patients previously treated for Paget's disease, an apparent resistance to treatment with AHButBP was observed. However, in these patients both serum alkaline phosphatase and urinary hydroxyproline fell to or even below the nadir values which had previously been achieved with C12MBP, irrespective of the degree of relapse. Thus the degree of suppression of Paget's disease of bone, achievable after treatment with bisphosphonates, seems to be constant for each patient, such that normal levels of serum alkaline phosphatase and urinary hydroxyproline cannot usually be attained in patients with extremely active disease.

Alendronate↗

Dichloromethylene-diphosphonate in patients with prostatic carcinoma metastatic to the skeleton.

A total of 17 patients with multiple osteoblastic bone metastases owing to prostatic carcinoma was treated with 2-dichloromethylene-diphosphonate, a powerful inhibitor of bone resorption. The drug was given intravenously (300 mg.) for 2 weeks and then orally (3,200 mg.) or intramuscularly (100 mg.) for 4 to 11 weeks. A definite improvement in pain, assessed by daily consumption of analgesic drugs and by an analogic scale, was observed within 10 days in 16 of the 17 patients. Four patients confined to bed rest for pain were able to walk after 2 weeks and reversal of paralysis also was noted in 1 patient. Transient changes in serum calcium (decreasing) and alkaline phosphatase (increasing) were observed in most patients. In the 3 patients in whom it was performed, repeated bone scanning showed a partial regression of pathological areas in 2 and the complete disappearance of most pathological areas in 1. Our results suggest that 2-dichloromethylene-diphosphonate may represent an important supportive treatment in patients with bone metastases owing to prostatic carcinoma, providing sustained relief of pain and regression of bone destruction without undesirable side effects.

Adult↗

Sequential treatment of Paget's disease with human calcitonin and dichloromethylene diphosphonate (Cl2MDP).

Dichloromethylene diphosphonate (Cl2MDP), a powerful inhibitor of bone resorption, was given (daily dose: 500 mg i.v. for 2 months and then 1600 mg p.o.) to five patients with Paget's disease after 8 months treatment with 50-100 MRC u/day of human calcitonin (CT). During treatment with CT plasma alkaline phosphatase (ALP) and urinary hydroxyproline (HOP) levels fell to about 60% of pretreatment values within the first 2 months in all the patients. Cl2MDP therapy resulted in a further drop of urinary HOP to 20% of baseline values, while serum ALP rose impressively during the first 2 weeks of therapy and then slowly fell to 25% of baseline values. We conclude that Cl2MDP can induce a further biochemical response after the so-called plateau phenomenon to CT and that it may represent the therapy of choice for severe Paget's disease.

Aged↗

Total and free PSA serum concentrations are not influenced by extensive physical exercise and bicycle riding.

Vigorous and prolonged physical exercise and mechanical involvement of the perineal region might influence prostatic function and measurement of both total (PSA) and free prostate specific antigen (fPSA), decreasing the diagnostic efficiency of the laboratory screening for either benign or neoplastic prostate disorders in athletes. To investigate the effects of regular and strenuous physical exercise with or without bicycle riding on integrity and biochemical function of prostatic tissue, we measured serum PSA and fPSA in 69 elite and professional cyclists, 31 members of the Italian national cross-country ski team, and in 43 sedentary healthy controls. The concentration of both PSA and fPSA did not differ significantly between sedentary individuals and physically active cross-country skiers (PSA 0.43 +/- 0.30 vs. 0.36+/-0.25, ns; fPSA 0.16+/-0.12 vs. 0.12+/-0.12, ns) or cyclists (PSA 0.43 +/- 0.30 vs. 0.36 +/- 0.23, ns; fPSA 0.16 +/- 0.12 vs. 0.13 +/- 0.08, ns), and the relative distribution of values appeared almost overlapping. We hypothesize that neither a heavy and regular physical exercise nor the extensive and prolonged mechanical involvement of the prostate region by the bicycle riding have significant influence on release of both PSA and fPSA.

Adult↗