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Biomedical subjects

O L Silva

Publications and source records attributed to O L Silva.

At least 19 recordsLinked to original sources

Serum procalcitonin as an index of inhalation injury in burns.

The molecular heterogeneity of serum immunoreactive calcitonin (iCT) was analyzed from a prospective study of 41 burn patients. Using different region-specific anticalcitonin antisera, the ratio of mid-region-recognizing to carboxyl terminal-region-recognizing iCT was found to increase acutely in those who subsequently died. The highest ratios occurred in those who died early of respiratory complications. Sephadex chromatography and reversed-phase HPLC demonstrated that the serum iCT circulated predominantly in the large molecular mass prohormone form (16 kDa). In comparison, iCT of normal human lung and of normal thyroid was shown to consist primarily of smaller monomeric mass forms. Furthermore, in 12 normal volunteers who were evaluated with a calcium-pentagastrin infusion, the ratio of iCT levels did not differ from the baseline ratio despite a 50% increase in serum iCT. These results suggest that in burns, the inhalational injury-associated hypercalcitonemia is characterized by a preferential release of procalcitonin; a form of constitutive secretion. The measurement of serum procalcitonin levels would appear to be a useful prognostic indicator of the severity of inhalational injury occurring in burn patients.

Biomarkers

Calcitonin as a marker for bronchogenic cancer: a prospective study.

A prospective study was done of serum calcitonin (HCT) levels in 61 patients with bronchogenic cancer. Initially, 52% of patients had hypercalcitonemia. Hypercalcitonemia was not confined to patients with any particular histologic type. Seventy-eight percent of those with high calcitonin remained normocalcemic. There was no correlation between high calcitonin levels and osseous metastases. Selective thyroid venous sampling delineated two types of hypercalcitonemia: thyroidal and ectopic. To date, the ectopic type has been associated with the small cell bronchogenic carcinoma. High initial calcitonin levels decreased significantly in 75% of patients on antitumor therapy. In 13 evaluable patients calcitonin levels mirrored clinical status changes 67% of the time. Calcitonin may be a useful marker to assess the results of therapy in patients with bronchogenic cancer.

Bone Neoplasms

Urine calcitonin as a test for medullary thyroid cancer: a new screening procedure.

Although the radioimmunoassay of serum calcitonin (CT) has facilitated the diagnosis of medullary thyroid cancer (MTC) one may encounter patients whose basal serum levels of CT are normal or nearly normal. In such cases clinicians have utilized intravenous stimulation tests such as calcium or pentagastrin to obtain a diagnostic increase in serum CT. We have reported finding immunoreactive CT in the urine of man and have found it to be a useful technique for the diagnosis and study of patients at risk for MTC or other hypercalcitonemic diseases. Using basal urine CT alone we were able to separate 73% of patients at risk for MTC into clearly normal or abnormal groups. For the remaining 27% a stimulation test with subsequent determination of urine CT was required. The radioimmunoassay of urine CT is a simple, reliable, accurate test for the screening diagnosis of MTC. A protocol for the screening workup of a patient at risk for MTC is given.

Adolescent

Calcitonin in extrathyroidal tissues of man.

Prior studies have demonstrated detectable immunoreactive calcitonin in the serum and urine of totally thyroidectomized humans, suggesting that the hormone may be secreted by extrathyroidal tissues. Accordingly, a study of the immunoreactive calcitonin content of human tissues was undertaken, utilizing autopsy material from 23 patients. Significant amounts of calcitonin were found in many extrathyroidal tissues, ranging up to 40 ng/g wet weight. The hormone was detectable with two antibodies having different region specificities for calcitonin. Gel filtration and subsequent radioimmunoassay demonstrated that extrathyroidal tissue has calcitonin fractions of the same molecular size and charge characteristics as do the serum and thyroid. The finding of large amounts of extrathyroidal calcitonin may explain why thyroidectomy in man is not accompanied by marked changes in calcium metabolism.

Adolescent

Salmon calcitonin in hypercalcemia.

We have undertaken a study of 24 hypercalcemic patients with the use of salmon calcitonin as a therapeutic agent. Seventy-five percent of the patients exhibited a clinically significant decrease in serum calcium and approximately half became normocalcemic within 2 hr. Throughout salmon calcitonin administration, the mean serum calcium of the patients was lower than the pretreatment values. Although the drug did not always lower the calcium level to normal, it often brought the hypercalcemia to more tolerable levels. During the course of calcitonin therapy, the number of patients with normal or near-normal serum calcium ranged from 31.3% (at 96 hr) to 82.4% (at 30 hr). Many of the patients improved symptomatically. The only significant side effects were nausea and vomiting in 12.5% of the patients, which necessitated cessation of therapy in only one. The drug was well tolerated in patients with azotemia. Calcitonin-induced hypocalcemia was not encountered. Salmon calcitonin can be used safely alone or in conjunction with other hypocalcemic therapies.

Aged

Calcitonin heterogeneity in lung cancer and medullary thyroid cancer.

An investigation was made of the increased serum calcitonin in patients with medullary thyroid cancer and bronchogenic carcinoma in order to determine whether these conditions can be differentiated immunochemically. Exdogenous fractions of immunoreactive calcitonin were separated by gel filtration and radioimmunoassayed with calcitonin antibodies having different region specificities. The pattern of serum heterogeneity of patients with medullary thyroid cancer was characterized by the presence of at least seven different fractions of immunoreactive calcitonin, ranging from fraction I (greater than or equal to 30 000 molecular weight (MW) to fraction V (approximately 2500 MW). In contrast, most patients with bronchogenic cancer had a predominance of high MW fractions (i.e. fractions I and IIA). Following in vitro incubation of the serum, the typical MW pattern of bronchogenic cancer serum could be converted to the more diffuse pattern seen in the serum of medullary thyroid cancer. We were able to differentiate, pre-operatively, the hypercalcitonaemia serum of medullary thyroid cancer patients from that of bronchogenic cancer patients by determination of the ratio of calcitonin as radioimmunoassayed with midportion versus carboxyl terminal antibody.

Calcitonin

Immunochemical heterogeneity of calcitonin in man: effect on radioimmunoassay.

Determinations of blood levels of human calcitonin by radioimmunoassay have varied considerably in different laboratories. Much of the controversy over calcitonin levels can be attributed to the multiplicity of immunoreactive forms of the hormone (iCT), the differing region specificities of the antisera utilized for measurement by radioimmunoassay, protein effects, different rates of degradation of the various iCT fractions and the specific methodology of the radioimmunoassay.

Antibody Specificity

Calcitonin levels in chronic renal disease.

High levels of serum calcitonin were found in patients with chronic renal failure. Serum calcitonin correlated directly with the phosphate to total calcium ratio; calcitonin levels correlated inversely with serum calcium in those patients on dialysis and directly with serum calcium in nondialysis patients. All patients had elevated serum gastrin. The high levels of serum calcitonin usually decreased following successful kidney transplantation. The pathophysiology of this hypercalcitonemia and its relationship to renal osteodystrophy and the disordered calcium metabolism of uremia remains to be elucidated.

Adult

Increased serum calcitonin levels in bronchogenic cancer.

A study of 26 men with bronchogenic cancer demonstrated high serum calcitonin levels in 62 percent (16). Levels were particularly high in patients with small-cell cancer and adenocarcinoma. Two varieties of hypercalcitonemia have been encountered: (1) ectopic hypercalcitonemia, in which the hormone is secreted by the tumor, and (2) thyroidal hypercalcitonemia, in which the high values emanate from the thyroid gland. In several patients, serum calcitonin levels decreased following therapy for the cancer. Further studies are needed to evaluate the diagnostic value and clnical utility of serum calcitonin levels as a marker substance in bronchogenic cancer.

Adenocarcinoma

Hypercalcitonemia in bronchogenic cancer. Evidence for thyroid origin of the hormone.

Retrograde venous catheterization in a hypercalcitonemic patient with adenocarcinoma of the lung demonstrated that the thyroid gland was secreting a very large amount of hormone (14-fold higher than the peripheral level), while the venous drainage from the tumor deposits was similar in concentration to that of the periphery. Conceivably, the calcitonin is being elaborated in response to metastatic and humoral bone resorption or both. Radiotherapy resulted in a decrease in the calcitonin level. Further studies are needed to determine the diagnostic or prognostic implications of serum calcitonin in bronchogenic cancer.

Calcitonin

In vitro studies of calcitonin release in man.

The influence of various agents on calcitonin release from human thyroid was studied in vitro. Under the condition of this investigation, calcium, magnesium and phosphate did not stimulate calcitonin release from short-term incubated slices of human thyroid. However, pentagastrin and USP glucagon were potent stimulators of calcitonin release. Theophylline and dibutyryl cyclic AMP were also potent stimuli. A highly purified preparation of pancreatic glucagon was without an effect. Those agents which stimulated calcitonin release were associated with augmented cyclic AMP accumulation. Although maximal discharge of calcitonin required the presence of calcium, out in vitro experiments raise the question as to whether a gastrointestinal hormone, rather than calcium, might not be the principal agent affecting calcitonin release.

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