Researching, monitoring and treating osteoporosis in a Sarcoid Clinic: seven years of experience and follow-up.
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Biomedical subjects
Publications and source records attributed to G Rizzato.
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Hard metal pneumoconiosis is an occupational pulmonary disease caused by long-term exposure to dust produced in the hard metal industry. In vitro experiments have been carried out to study the solubility and metabolic behaviour in human lung tissue and plasma of hard metal alloy constituents such as cobalt, tungsten, tantalum, titanium and niobium. The experiments were carried out using 60Co, 187W, 182Ta, 44Ti and 95Nb radiotracers in combination with neutron activation, radio-release tests and gel filtration techniques. Leaching experiments from neutron-irradiated hard metal dust showed that cobalt was highly soluble, especially in the lung cytosol and plasma, in comparison with tantalum and tungsten. The gel filtration experiments showed three biochemical pools of cobalt in both lung and plasma components, in accordance with the hypothesis that cobalt represents the allergic factor in the development of hard metal disease. High affinity for proteins was observed for Nb, Ta and Ti, but not for W, in agreement with the dissimilar biological half-lives of these elements in the body. The different ability of the metals to interact with biochemical components and to be solubilized in biological media may explain the various degrees of retention in the lung, which would influence the metabolic pathways. This would explain the presence of Co, Ta and W in body fluids, as well as in the public hair and toenails of hard metal workers.
The presence of retroperitoneal lymphnodes is well known in sarcoidosis. We observed in two patients unilateral hydronephrosis (asymptomatic in one; dysuria in the other), and in one patient urine retention due to compression of both ureters; this patient also had jaundice due to lymphnode compression of the biliary tract. In another four patients we noted retroperitoneal lymphnodes without compression. We conclude that retroperitoneal impairment may be a previously unreported complication of Sarcoidosis.
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The incidence of glucocorticoid-induced osteoporosis is reported in about 40 to 50% of treated patients, but it has never been extensively studied in sarcoidosis. We have studied Vertebral Cancellous Mineral Content (VCMC) of the lumbar spine by Quantitative Computed Tomography (QCT) in 190 normal subjects, 7 patients with sarcoid on no treatment and 64 patients with sarcoid on treatment with prednisone. As compared to the 190 normal subjects and the 7 untreated patients, VCMC was reduced in 46 of 64 patients with sarcoid on treatment with prednisone. Loss of VCMC in the patients varied directly with dose and duration of prednisone treatment. It is concluded that - in sarcoid patients and especially in postmenopausal females - long-term prednisone therapy results in bone mineral loss more frequently than elsewhere reported for other groups of patients. It is not clear if this difference is due to the sarcoidosis itself or to the better sensitivity of Computed Tomography compared to former techniques.
Prednisone-induced osteoporosis is very frequent in the long-term treatment of sarcoidosis (sarcoidosis 4:45-48, 1987). The aim of this work is to evaluate if salmon Calcitonin (sCT) is able to prevent osteopenia in the long-term. We have studied 53 patients with chronic histologically-proven sarcoidosis, all needing steroids, in a follow-up of 15 months; 20 of them were protected with sCT (100 I.U. i.m. daily for one month, then every two days for all the time of the study), 33 were unprotected. The two groups were matched for age, sex and total dose of prednisone. In order to overcome the differences of Vertebral Cancellous Mineral Content (VCMC) due to age and sex, we express VCMC in terms of Z score, i.e. the number of standard deviations above or below our normal means: initial Z score was -1.77 +/- 0.16 in the sCT group and -0.99 +/- 0.17 in the other group (P less than .05). For each subject we calculated the Mineral Loss (ML) in % of the initial value. At the end of the study ML% averaged -2.15(+/- 2.27) in the sCT protected group, and -14.11(+/- 2.08) in the unprotected group (P less than .001). We have also analysed the results limited to pts with initial Z score under -1 (19 sCT protected pts vs 18 unprotected). In these subgroups the ML% after 15 months averaged -13.62(+/- 2.9) in the unprotected group and -2.80(+/- 2.29) in the protected one (P less than .01). Finally we have studied another subgroup, i.e. 21 postmenopausal females: 9 were sCT protected, 12 were unprotected.(ABSTRACT TRUNCATED AT 250 WORDS)
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Eighty-four normal subjects, 5 untreated sarcoid patients and 32 sarcoid patients under chronic prednisone therapy were submitted to Quantitative Computed Tomography (QCT) for Vertebral Cancellous Mineral Content (VCMC) evaluation. In the five untreated and in the 84 normal subjects, VCMC (given in mg/cm3) fell in the normal range found elsewhere. 22 of the 32 treated patients had lower than normal values. Osteoporosis (expressed through cancellous mineral loss) increased significantly (P less than .01) with increasing dose x time of prednisone therapy. We conclude that the bone loss is far more frequent than suspected in prednisone treated patients with sarcoidosis; yearly QCT could be a good tool for monitoring patients under chronic therapy.
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Fifty-eight contributors from 12 European and 2 American sarcoidosis centers have collaborated in a survey to define many questions concerning the use of 67Ga lung scan in sarcoidosis. The new quantitative scoring methods based on digital evaluation seem better in detecting lung activity. In 20.1% of untreated patients, the 67Ga lung scan appeared to be the only noninvasive method with which clinical activity could be detected. 67Ga scans may be useful in guiding lung biopsy and in choosing pulmonary segments for BAL. Of 382 patients studied during follow-up (154 patients with three to nine scans at intervals of 2 to 12 months), the 67Ga scan was far more sensitive than chest radiography, both in detecting improvement and in foreseeing relapses. Steroid therapy appears to suppress ACE levels more than 67Ga uptake, and 67Ga uptake more than the alveolitis detectable by BAL. Gallium-67 uptake rebounds to positivity occur in about 40% of patients after steroid discontinuation and in about 20% of patients after steroid reduction to daily doses of 10 mg or less of prednisone. The 67Ga dose of 1.5 mCi seems appropriate for clinical purposes and is recommended for the subjective scoring method in order to reduce the cost and the radiation burden.
The effects of Captopril, an angiotensin-converting enzyme inhibitor, on pulmonary hemodynamics and blood gases were studied in 9 patients with chronic obstructive lung disease (COLD) and pulmonary hypertension (PA-P greater than 20 mm Hg). Hemodynamic data were recorded prior to Captopril administration (50 mg per os) and for the next 60 min. Following Captopril administration, significant reductions in mean pulmonary artery pressure (PA-P) (p less than 0.05), in mean pulmonary wedge pressure (PW-P) (p less than 0.05), and in total pulmonary resistance (TPR) were noted; significant reductions in mean brachial artery pressure (BA-P) and systemic vascular resistance (SVR) were also recorded, while cardiac output, heart rate and blood gas tensions showed no significant changes. Furthermore, the higher the hypoxemia, the greater was the reduction in BA-P (p less than 0.05). We therefore feel that Captopril, when administered to COLD patients with pulmonary hypertension, may protect the pulmonary circulation from hypoxic pulmonary vasoconstriction.
A male subject exposed for many years to metal dusts from grinding and cutting hard metals was investigated four years after the exposure ceased. While chest x-ray films and histologic examinations showed diffuse interstitial fibrosis and severe perivascular and peribronchiolar fibrosis, radiochemical neutron activation analysis (NAA) showed high W, Ta and Co concentrations in the pulmonary specimen compared to the corresponding determinations in 17 control subjects. Tantalum was also found in high concentrations in bronchoalveolar lavage fluid (BAL) and in the blood. In addition other elements such as Ni, Cr, Th and Cd were found in the lung biopsy specimen of the worker in amounts significantly higher than in the control subjects. The results suggest that hard metal origin of pulmonary fibrosis can be detected many years after removal from exposure.
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