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J Pallotta

Publications and source records attributed to J Pallotta.

17 recordsLinked to original sources
PubMed1997

The effect of PTH antagonist BIM-44002 on serum calcium and PTH levels in hypercalcemic hyperparathyroid patients.

BIM-44002, a pure competitive antagonist of parathyroid hormone (PTH), has a high affinity for the PTH/PTHrP receptor in vitro, and can completely inhibit the actions of a PTH agonist in rats in vivo. Toxicology studies in rats and dogs showed BIM-44002 to be devoid of any adverse effects. Therefore we undertook an investigation to evaluate the potential utility of BIM-44002 in lowering elevated serum calcium in three patients with primary hyperparathyroidism. BIM-44002 was administered by continuous intravenous infusion at dosages of 100 microg/hour (370 nmol/hour) for 12 hours, followed by 200 microg/hour for 12 hours, followed by 400 microg/hour for 12 hours. Vital signs and serum ionized and total calcium were monitored hourly and for 3 hours after cessation of the infusion. Blood for PTH determinations was obtained at the same time points. Serum calcium and PTH did not change during and after the infusion of the antagonist. No subject experienced any adverse reactions to the infusion of the antagonist. We conclude that although the PTH antagonist BIM-44002 was effective both in vitro and in vivo in animals, and it was safe in humans, it was not able to lower serum calcium in patients with hyperparathyroidism. Possible reasons for lack of clinical efficacy are discussed.

Adult↗
PubMed1994

A prospective study of family environments of children hospitalized for nonorganic failure-to-thrive.

Family functioning of nonorganic failure-to-thrive (NOFT) infants was compared with that of physically healthy, normally growing infants of similar socioeconomic status shortly after the time of the diagnosis of this condition (average age of 5 months) and again at 4 years of age. Families of NOFT infants demonstrated less adaptive relationships than did comparison-group infants, as measured by the Family Relationships Inventory (FRI) at both time points, but a comparable number of changes in residence and constellation on follow-up. Contrary to prediction, the quality of family relationships at point of diagnosis did not predict subsequent family relationships, residence, or constellation changes in the NOFT sample. However, more adaptive family relationships in the comparison group at study entry predicted fewer residence and constellation changes and more cohesive relationships 3 years later. The impact of significant discontinuities in family functioning and status should be considered in research and in clinical interventions with NOFT children.

Child, Preschool↗
PubMed1990

Maternal interactional behavior with nonorganic failure-to-thrive infants: a case comparison study.

Mothers of 47 6-month-old infants with early histories of nonorganic failure to thrive (NOFT) infants and a matched comparison group of physically healthy infants were observed in interactions with their infants in their homes one month following hospitalization. Mothers of NOFT infants were observed to have less adaptive social interactional behavior, less positive affective behavior, and demonstrated more arbitrary termination of feedings. No group differences were found in flexibility or sensitivity of maternal feeding, or in environmental circumstances such as number of persons present, noise level, or level of activity. These salient deficiencies in maternal interactional behavior may continue to disrupt the NOFT child's physical growth and psychological development following initial diagnosis and hospitalization. Additional studies are needed to identify patterns of maternal interactional behavior which influence psychological prognosis and to assess the responsiveness of maternal interactional behavior to intervention.

Adult↗
PubMed1989

Parathyroid localization, three-dimensional modeling, and percutaneous ablation techniques.

When available, state of the art noninvasive localization studies should be utilized routinely in previously unexplored patients for localizing parathyroid pathology, even when exceptional surgical experience exists. These studies can both minimize the 3 to 20% incidence of missed pathology and promote an approach of limited neck exploration with consequent lowering of morbidity, complications, and costs. Choice of imaging modalities for localizing these small masses is largely dependent on the level of state of the art of available equipment, the interest and experience of the performing physicians, and the attention to technical detail for each of the modalities at an individual institution. In choosing a single test, CT, and most recently cine CT with three-dimensional modeling, is favored because of higher probability of providing the kinds of information most useful to the surgeon. This includes precise anatomic localization and identification of locations likely to be missed by the surgeon (such as mediastinum, deep neck) and the capability for predicting multiple gland disease, for detecting smaller lesions, and for lower incidence of false-positive results. Ultrasound is attractive because of the low cost and noninvasiveness, and it is particularly sensitive in the thyroid region and upper neck. In difficult cases, CT, cine CT, and ultrasound may be augmented by needle aspiration of fluid for PTH assay. Thallium-technetium scanning and MRI are useful alternatives. In the previously explored patient and in patients with difficult diagnostic problems (such as ectopic adenoma, parathyroid carcinoma), the use of multiple noninvasive studies is strongly recommended, preferably CT (particularly, cine CT with three-dimensional imaging) and isotope scanning or MRI. The concurrence of two or more of these studies has a relatively high predictive value (82 to 88%) for localization. However, highly selective venous catheterization and selective magnification arteriography remain the most accurate modalities in these patients (91 to 95% sensitivity with few false-positive results) and may be combined with interventional radiologic techniques for tumor ablation in selected patients without compromising subsequent surgical alternatives. Stereotactic ablation techniques are in development.

Catheterization, Peripheral↗
PubMed1985

Regulation of parathyroid hormone release and cytosolic calcium by extracellular calcium in dispersed and cultured bovine and pathological human parathyroid cells.

Alterations in parathyroid glandular sensitivity to calcium may contribute to the hypersecretion of PTH in hyperparathyroidism. Since the cytosolic calcium concentration may mediate the effects of extracellular calcium on PTH release, we have employed the calcium-sensitive intracellular dye QUIN-2 to examine the relationship between extracellular calcium, cytosolic calcium, and PTH secretion in adult, neonatal, and cultured bovine as well as pathological human parathyroid cells. PTH release was measured using C- and N-terminal radioimmunoassays. Neonatal bovine parathyroid cells showed a greater set-point for secretion (the Ca++ concentration causing half of the maximal inhibition of PTH release) than adult cells (1.27 +/- 0.11 vs. 1.06 +/- 0.11 mM extracellular calcium, P less than 0.01), and a slightly higher extracellular calcium was necessary to raise the cytosolic calcium concentration to a given level in neonatal than in adult bovine parathyroid cells. In individual neonatal and adult cell preparations, there was a close correlation between the set-point for secretion and the "set-point" for cytosolic calcium (r = 0.832, P less than 0.001). In cells from five human parathyroid adenomas, which had an increase in set-point for secretion, the extracellular calcium concentration necessary to raise the cytosolic calcium concentration to a given level was slightly greater than in the neonatal cells. In four preparations of human parathyroid cells there was a significant correlation between the set-points for secretion and cytosolic calcium (r = 0.856, P less than 0.01). Because neonatal bovine and pathological human parathyroid glands show cellular hyperplasia, we studied the temporal relationship between cellular proliferation and the regulation of PTH release and cytosolic calcium concentration in cultured bovine parathyroid cells. Cellular proliferation, estimated by 3H-thymidine incorporation, increased significantly in culture from 104 +/- 10.1 counts/well on day 1 (first 24 h in culture) to 588 +/- 188 and 6,156 +/- 649 counts/well on days 2 and 4, respectively. In cultured cells on day 1, highly Ca++ (2-3 mM) inhibited maximal PTH release by 58.8 +/- 3.2%, which decreased significantly (P less than 0.001) to 38.2 +/- 1.9 and 17.1 +/- 3.7% on days 2 and 4, respectively. The cytosolic calcium observed at 3 mM calcium on day 1 was 701 +/- 43 nM, which declined to 466 +/- 60 and 314 +/- 14 nM on days 2 and 4 (P less than 0.05). There was a close correlation between this progressive decrease in maximal inhibition of PTH release and the cytosolic calcium at high extracellular calcium in cultured cells (r = 0.99, P < 0.001). Thus, during active proliferation of cultured cells, there is an alteration in the regulation of cytosolic calcium at a given extracellular calcium concentration, and changes in the regulation of PTH release and cytosolic calcium by extracellular calcium may be related to enhanced cellular proliferation.

Animals↗
PubMed1982

Effect of hyperparathyroidism and hypercalcemia on lower esophageal sphincter pressure.

Heartburn is a frequent and sometimes initial complaint in hyperparathyroidism, and it is often relieved by successful parathyroid surgery. Four of five patients with primary hyperparathyroidism and heartburn obtained relief of symptoms and had an increase in lower esophageal sphincter pressure after successful operative treatment. Four of five volunteers undergoing calcium infusion exhibited a decrease in lower esophageal sphincter pressure after about 2.5 to 3 hours of infusion. Calcium infusion in a treated patient who had an increase in lower esophageal sphincter pressure postoperatively resulted in a transient return of lower esophageal sphincter pressure to preoperative levels.

Calcium↗
PubMed1982

Abnormal regulation of parathyroid hormone release by calcium in secondary hyperparathyroidism due to chronic renal failure.

Dispersed parathyroid cells were employed to study calcium-regulated parathyroid hormone (PTH) release in severe secondary hyperparathyroidism due to chronic renal insufficiency. Cell preparations were obtained from 16 parathyroid glands of 6 patients undergoing subtotal parathyroidectomy for parathyroid bone disease and/or hypercalcemia. The effects of increasing ambient calcium concentration on immunoreactive PTH release in vitro were assessed and compared with results observed in cells prepared from 7 adenomas and 6 normal parathyroid glands. There was no difference in maximal PTH release for the 3 types of tissue (mean +/- SEM, 8.48 +/- 1.9 , 8.1 +/- 3, and 10.1 +/- 0.78 ng/10(5) cells. h respectively). In 14 of 16 hyperplastic glands, 6 of 7 adenomas, and all of the normal glands, PTH release was inhibited more than 50% by 2-3 mM calcium (suppressible glands). Of the normal glands, half of the maximal inhibition of PTH release (the set-point) occurred at less than 1.03 mM calcium in 5 of 6 cases. In 12 of 14 suppressible hyperplastic glands and all of the 6 suppressible adenomas, on the other hand, the set-point was 1.03 mM or higher (p less than 0.01 and P less than 0.002, respectively). Thus, in severe secondary parathyroid hyperplasia due to chronic renal insufficiency, there is frequently an increase in the set-point for calcium without a change in the maximal secretory rate per cell. Abnormal calcium-regulated PTH release at the cellular level, therefore, is not limited to parathyroid neoplasia (i.e. adenoma or primary hyperplasia), but may occur in secondary hyperplasia as well.

Adenoma↗
PubMed1982

Impaired in vivo insulin clearance in patients with severe target-cell resistance to insulin.

The concentration of insulin in plasma is determined by both its rate of secretion and its rate of clearance from the plasma compartment. The effect of marked insulin resistance on insulin clearance in vivo has not been determined in man. We have employed the euglycemic insulin clamp technique to measure insulin sensitivity and insulin clearance in 16 control subjects and in 4 subjects with marked target-cell resistance to insulin. Two insulin-resistant patients had reduced receptor concentration on peripheral mononuclear cells, and two patients had normal receptor number and affinity. During 80-mU/m2/min insulin clamp studies, the clearance rate in each insulin-resistant patient was lower than that in any controls; the mean insulin clearance rate was 511 +/- 74 ml/m2/mon in control subjects and 205 ml/m2/min (P less than 0.001) in insulin-resistant patients. These findings demonstrate an association between marked target-cell resistance to insulin and impaired in vivo insulin clearance, and suggest an important role for receptor-mediated pathways in insulin clearance in vivo.

Adult↗
PubMed1980

Parathyroid adenomas: cinearteriography.

Parathyroid adenomas in an ectopic location, either the mediastinum or high in the neck, can be relatively easily identified arteriographically because the lesions are separate from the thyroid gland and therefore are not confused with it. However, in most cases in which the adenoma is situated adjacent to thyroid tissue (85%-90%), arteriographic identification, particularly when the lesion is small, may be extremely difficult. Cineangiography during parathyroid arteriography has been found extremely helpful in positive identification of these juxtathyroidal adenomas. Movement of the head from side to side and swallowing maneuvers during cine recording of a selective arteriogram allow determination of the location of a suspicious "blush" in relation to the thyroid gland. As a rule, parathyroid adenomas stain densely in the tissue phase, are nearly always posterior to the thyroid, and separate from thyroid tissue on swallowing. In 10 of 14 parathyroid arteriographic examinations, cinearteriography was useful in confirming or excluding a parathyroid adenoma.

Adenoma↗
PubMed1979

Complete remission of acromegaly with medical treatment.

A 40-year-old patient with a ten-year history of acromegaly had persistent disease despite prior treatment with conventional pituitary radiotherapy and two transsphenoidal hypophysectomies. Initial evaluation showed characteristic acromegalic features, hypertension, amenorrhea, inappropriate diaphoresis, and poorly controlled diabetes mellitus despite isophane insulin suspension daily. Growth-hormone levels were high and did not suppress with glucose load. Treatment with bromocriptine was associated with prompt improvement in glucose intolerance, with elimination of insulin requirement within 72 hours of institutions of this therapy. Blood pressure normalized; inappropriate diaphoresis disappeared. Within three months ovulatory menses were noted to resume for the first time in ten years. There was progressive improvement in the soft-tissue changes of acromegaly. The growth-hormone levels fell within three hours after the first dose of bromocryptine and remained suppressed throughout her six-month course of therapy.

Acromegaly↗
PubMed1976

Galactorrhea-amenorrhea syndromes: etiology and treatment.

Fifteen patients with galactorrhea-amenorrhea syndromes were studied before, during, and after treatment with bromergocryptine. Galactorrhea and amenorrhea were noted after pregnancy (6 patients), after oral contraceptive therapy (5 patients), and in association with pituitary adenoma (4 patients). Before treatment prolactin values were elevated ranging from 27 to 125 ng/ml, while luteinizing hormone and progesterone levels failed to show ovulatory peaks or luteal phase progression. Eleven patients had luteinizing hormone-releasing hormone tests before therapy. Response was normal in 8, subnormal in 2 pituitary adenoma, and supranormal in 1 patient with premature ovarian failure. Treatment with bromergocryptine was associated with a lowering of serum prolactin, cessation of lactation in all, and return of ovulatory menses in 14 of 15 patients. All relapsed when therapy was discontinued. Four patients became pregnant while on therapy. Long-term bromergocryptine therapy is effective for all forms of galactorrhea-amenorrhea syndromes studied.

Adenoma↗