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Biomedical subjects

S J Marx

Publications and source records attributed to S J Marx.

At least 145 records · Page 8Linked to original sources

Computerized technetium/thallium scans and parathyroid reoperation.

Twenty-three consecutive patients who underwent reoperation for persistent primary hyperparathyroidism were studied with computerized technetium/thallium scans to evaluate it as a localization test. Prospective and blinded retrospective readings of the scans were correlated with findings at surgery. Computerized technetium/thallium scanning detected 52% of the parathyroid adenomas found at surgery. Forty-two percent of adenomas were localized exactly. There were no false positive scans. No normal parathyroid glands were imaged. No mediastinal glands were imaged. The study was not observer dependent. We conclude that computerized technetium/thallium scanning is helpful in patients undergoing parathyroid reoperation. If positive, it can accurately localize adenomas. If negative, we recommend more invasive studies.

Adenoma↗

Vitamin D3--resistant fibroblasts have immunoassayable 1,25-dihydroxyvitamin D3 receptors.

Cultured fibroblasts obtained from patients with tissue resistance to 1,25-dihydroxyvitamin D3 (vitamin D3--dependent rickets, type II) contain normal, low, or undetectable concentrations of this hormone's receptor protein as measured by a ligand-binding assay. Extracts from these cells were evaluated for receptors by immunoassay with a recently developed monoclonal antibody to the chick receptor. The results show that a protein sedimenting at 3.7S and recognizable by the antibody exists in comparable concentrations in cells from both normal and resistant patients, irrespective of the hormone-binding abnormalities of the cells. This implies that deficiencies in hormone binding associated with inherited tissue resistance to 1,25-dihydroxyvitamin D3 probably arise from structural variations in the receptor molecule and not from defective receptor synthesis.

Antibodies, Monoclonal↗

Ultrasonic parathyroid localisation in previously operated patients.

Sixty-two patients with hyperparathyroidism and failed prior neck surgery were examined by ultrasound before reoperation to localise abnormally enlarged glands. If mediastinal lesions are excluded, a total of 57 glands greater than 5 mm in size were removed from 48 patients. Ultrasound demonstrated only 18 of these for a true positive rate of 32%. There were 39/57 (68%) false negatives. In addition, there were 16 false positives. In our experience, the detection rate of ultrasound for enlarged parathyroid glands in patients with failed surgery is significantly less than that reported in previously unoperated patients (73%), or in the limited number of reported cases of patients with previous operations (75%). Our high false negative rate is probably partially due to the large number of posteriorly located small glands which cannot be adequately visualised by ultrasound. Nevertheless, because of its non-invasive nature, low cost and ready availability, ultrasound should be utilised as an initial screening procedure in patients with failed previous surgery.

Adolescent↗

Intraoperative urinary cyclic adenosine monophosphate as a guide to successful reoperative parathyroidectomy.

Sixty patients with persistent or recurrent primary hyperparathyroidism underwent reexploration during which urinary cyclic adenosine monophosphate (UcAMP) levels were determined at half-hour intervals by radioimmunoassay. Retrospective analysis of the data allowed us to develop UcAMP criteria for surgical success. Following removal of parathyroid tissue, if an individual UcAMP level dropped 50% from the median baseline level, or if elevated levels dropped to less than 4.0 nmol/dl glomerular filtrate, surgery was predicted to be successful. Eight unsuccessful procedures in seven patients produced no decline in UcAMP, and the intraoperative results accurately predicted surgical failure. Fifty-three patients underwent successful procedures and in every case UcAMP fell. Ninety-eight per cent of these successful procedures were predicted by our criteria. Levels of UcAMP fell 1.5 +/- 0.5 hours (means +/- SD) following abnormal parathyroidectomy. In 19 of 36 successful cases diagnosed before surgery as adenoma, the operative procedure was terminated before a significant drop in UcAMP. In 16 of 17 successful cases diagnosed before surgery as hyperplasia or uncertain histology, UcAMP fell during the operation. Intraoperative determination of UcAMP is helpful in reoperative parathyroid surgery. The criteria established allow intraoperative prediction of success with remarkable accuracy. Urinary cyclic AMP is especially helpful in reoperation for multigland disease; when enough pathologic tissue has been removed, the criteria will be met and the procedure may be terminated with confidence.

Cyclic AMP↗

Parathyroid aspiration directed by angiography: an alternative to venous sampling.

Not all parathyroid glands can be visualized by CT or ultrasound and, therefore, cannot be aspirated using these techniques. We report the localization of a parathyroid gland by arteriography and needle aspiration under fluoroscopic guidance. This technique can be used to confirm a diagnosis of hypervascular parathyroid tissue that cannot otherwise be confirmed.

Adult↗

The effect of short term lithium administration on suppressibility of parathyroid hormone secretion by calcium in vivo.

We performed graded calcium infusions twice in six normal young men, once without medication and a second time after they had received therapeutic doses of lithium carbonate for 5 days. The serum lithium level was 0.73 +/- 0.08 meq/liter (mean +/- SE) at the beginning of the calcium infusion and reached 0.97 +/- 0.13 150 min after receiving a lithium dose (210 min after beginning the test). There was no significant difference in mean basal serum calcium, plasma PTH, or nephrogenous cAMP for the untreated and treated periods. There was also no significant difference in calcium suppressibility of PTH secretion, as reflected by changes in nephrogenous cAMP. Changes in plasma PTH in response to calcium infusion likewise did not differ for the two periods, with the exception of a slightly greater degree of suppression in the unmedicated state (77% vs. 57% on lithium: P less than 0.02, by paired t test) at the last time point of the calcium infusion. The data show that short term administration of therapeutic doses of lithium does not alter the set-point for calcium suppression of PTH secretion in man. Further studies of calcium suppressibility of PTH secretion in subjects receiving long term lithium therapy will be needed to evaluate the pathophysiology of lithium-induced hypercalcemia.

Adult↗

Hyperfunctioning cystic parathyroid glands: CT and sonographic findings.

Four functioning cystic parathyroid glands were evaluated with computed tomography (CT) and sonography in four patients, only one of whom had prior surgery. Sonography demonstrated solid lesions of decreased echogenicity with fluid-filled cavities near the lower thyroid poles or in the posterosuperior mediastinum. On CT the cystic parts of the lesions were of low attenuation (1-44 H), often with a well defined wall that was better demonstrated after intravenous contrast administration. Fine-needle aspiration biopsy of two of the cystic parathyroids revealed elevated parathyroid hormone levels. These lesions probably represent degenerating adenomas rather than true parathyroid cysts. While the CT and sonographic findings are nonspecific, the diagnosis of a cystic parathyroid should be entertained when a fluid-filled lesion is encountered in the neck of a patient with or without hypercalcemia. The diagnosis may be confirmed by assay of parathyroid hormone from the fluid aspirate.

Adenoma↗

Detection of mediastinal parathyroid glands by nonselective digital arteriography.

Six patients with failed previous operations and anterior mediastinal parathyroid glands were evaluated with selective angiography and nonselective arterial digital arteriography. Selective angiography depicted two of nine mediastinal glands; nonselective arterial digital arteriography depicted only one of nine mediastinal glands and missed a sizable (4.5 cm) gland demonstrated by routine arteriography. Nonselective arterial digital arteriography did not demonstrate any additional mediastinal glands. From this preliminary experience, it was concluded that nonselective arterial digital arteriography is not a sensitive method for detecting mediastinal glands.

Adult↗

The effect of the bicarbonate anion on serum ionized calcium concentration in vitro.

The effect of changes in bicarbonate ion concentration on calcium ion concentration was examined in vitro in serum and protein-free solution. The findings in this study support the formation of a calcium-bicarbonate complex (CaHCO3+) that has a KA of 5.20 in protein-free solution. [Ca++] varied inversely with [HCO3-] in both serum and protein-free solution. This variation was independent of the known variation of [Ca++] with pH. In serum [Ca++] varied 0.0036 mM Ca++ per 1 mM change in [HCO3-] compared with a variation of 0.0060 mM Ca++ per 0.01 unit change in pH. Addition of bicarbonate to serum (Pco2 constant) produced a 50% greater decrease in [Ca++] than that produced by a reduction in Pco2 which gave the same pH change. These findings indicate that abnormal bicarbonate concentrations should be considered when ionized calcium concentrations are estimated from total plasma calcium values in acid-base disorders. In metabolic acid-base disorders, the bicarbonate effect adds to the pH effect on calcium ion concentration. In compensated respiratory acid-base disorders, the bicarbonate effect subtracts from the pH effect on calcium ion concentration.

Acid-Base Imbalance↗

Persistent hyperparathyroidism caused by incomplete parathyroid resection and a hyperfunctioning parathyroid autograft.

A case of familial primary hyperparathyroidism occurred in which persistent hypercalcemia was caused by hyperplastic parathyroid tissue left in the neck and mediastinum after initial surgery and by a hyperfunctioning parathyroid autograft in the forearm. Successful therapy required parathyroid localization and resection of tissue from the neck, mediastinum, and forearm. Parathyroid tissue should be autotransplanted at the time of initial surgery only when total parathyroidectomy is judged likely to have been achieved.

Adult↗

Parathyroid hormone and vitamin D receptors.

Parathyroid hormone (PTH), an 84-amino-acid polypeptide hormone, interacts with plasma membrane-bound receptors on bone and kidney cells, thereby increasing intracellular cAMP. Although the synthetic amino terminal 1-34 fragment of PTH possesses full biological activity, there is no firm evidence that hormone cleavage is a requisite step in the biological action of PTH. In contrast, vitamin D must undergo hydroxylations in the 1 and 25 positions in order to become fully active on target organs. 1,25(OH)2D, a steroid-like hormone, interacts with cytoplasmic receptors in small intestinal and bone cells. The 1,25(OH)2D-receptor complex (in the same manner as other steroid hormones) directs the synthesis of specific proteins. The integrated actions of PTH and vitamin D maintain serum calcium within narrow limits, thereby permitting normal neuromuscular and secretory function, as well as normal bone mineralization. Abnormalities in hormone secretion (PTH) or metabolic activation (vitamin D) lead to clinical disturbances in hormone action. Abnormalities at the level of the receptor-effector system for PTH and vitamin D also lead to clinical disturbances characterized by resistance to hormone action. Specific examples of the latter include pseudohypoparathyroidism, in which deficient activity of a component (the G unit) of the adenylate cyclase complex may lead to resistance to PTH, and hereditary vitamin D-dependent rickets type II, in which abnormalities in the nuclear uptake of 1,25(OH)2D may lead to impaired response to 1,25(OH)2D.

Animals↗

Work in progress: abnormal parathyroid glands. Comparison of nonselective arterial digital arteriography, selective parathyroid arteriography, and venous digital arteriography as methods of detection.

Nonselective arterial digital arteriography (NSADA), selective parathyroid arteriography (SPA), and venous digital arteriography (VDA) were compared as methods of detecting parathyroid enlargement in 14 patients with primary hyperparathyroidism undergoing preoperative localization following unsuccessful neck surgery. All 14 had SPA and NSADA, consisting of contrast injections into the ascending aorta, innominate artery, and left subclavian artery; 7 also had VDA. Surgery was performed in 9 patients, and 2 additional glands were confirmed by fine-needle aspiration and venous sampling. Parathyroid glands could not be located in 3 patients, who were not re-explored. SPA demonstrated 11/13 abnormal glands (85%). NSADA detected 7/13 (54%), and there were 2 false positives. VDA showed 5/6 glands detected by NSADA (83%); the seventh patient did not have VDA. The overall quality of VDA was inferior to NSADA. Although NSADA and VDA are less sensitive than SPA, they are safer and easier to perform and should be the initial vascular screening procedures following unsuccessful parathyroid surgery.

Adult↗

Aspiration of enlarged parathyroid glands for parathyroid hormone assay.

Enlarged parathyroid glands were percutaneously aspirated under computed tomographic (CT) control in 7 patients, and levels of parathyroid hormone (PTH) and human thyroglobulin (HTg) were measured. All 7 patients had high levels of PTH in at least 1 specimen. It is concluded that the measurement of high concentrations of PTH in the aspirate from a cervical or mediastinal mass, with CT documentation of needle position, provides absolute localization of parathyroid masses.

Adenoma↗

Resistance to 1,25-dihydroxyvitamin D. Association with heterogeneous defects in cultured skin fibroblasts.

UNLABELLED: We evaluated the interaction of [3H]1,25(OH)2D3 with skin fibroblasts cultured from normal subjects or from affected members of six kindreds with rickets and resistance to 1-alpha, 25(OH)2D [1,25(OH)2D]. We analyzed two aspects of the radioligand interaction; nuclear uptake with dispersed, intact cells at 37 degrees C and binding at 0 degrees C with soluble extract ("cytosol") prepared from cells disrupted in buffer containing 300 mM KCl and 10 mM sodium molybdate. With normal fibroblasts the affinity and capacity of nuclear uptake of [3H]1,25(OH)2D3 were 0.5 nM and 10,300 sites per cell, respectively; for binding with cytosol these were 0.13 nM and 8,900 sites per cell, respectively. The following four patterns of interaction with [3H]1,25(OH)2D3 were observed with cells cultured from affected patients: (a) two kindreds; cytosol binding and whole-cell nuclear uptake both unmeasurable; (b) one kindred, decreased capacity and normal affinity both for binding in cytosol and for nuclear uptake in whole cells; (c) two kindreds, normal or nearly normal capacity and affinity of binding in cytosol but unmeasurable whole-cell nuclear uptake; and (d) one kindred, normal capacity and affinity of both cytosol binding and whole-cell nuclear uptake. In all cases where the radioligand bound with high affinity in nucleus or cytosol, the nucleus- or cytosol-associated radioligand exhibited normal sedimentation velocity on sucrose density gradients. When two kindreds exhibited similar patterns (i.e. pattern a or c) with the analyses of cultured fibroblasts, clinical features in affected members suggested that the underlying genetic defects were not identical. IN CONCLUSION: (a) Fibroblasts cultured from human skin manifest nuclear uptake and cytosol binding of [3H]1,25(OH)2D3 that is an expression of the genes determining these processes in target tissues. (b) Based upon data from clinical evaluations and from analyses of cultured fibroblasts, severe resistance to 1,25(OH)2D resulted from five or six distinct genetic mutations in six kindreds.

Cell Nucleus↗