Richard K. Donabedian

Rapid Parathyroid Hormone Analysis During Venous Localization

ObjectiveTo determine the usefulness of the rapid parathyroid hormone (PTH) assay during venous localization for primary hyperparathyroidism (1° HPTH). Summary Background DataRemedial exploration for persistent 1° HPTH poses a significant challenge when noninvasive preoperative localization studies are negative. Based on experience with the intraoperative rapid PTH assay, this technique was extrapolated to the interventional radiology suite and generated near real-time data for the interventional radiologist employing on-site hormone analysis, with a 12-minute turnaround time from blood sampling to assay result. MethodsBetween November 1997 and July 2002, 446 patients with 1° HPTH were referred for treatment. Of these, 56 (12.5%) represented remedial patients who had each undergone one or more previous cervical explorations. Noninvasive imaging studies were positive for or suggestive of localized disease in 49/56 (87.5%) of these patients, who therefore proceeded directly to surgical exploration. Seven patients with persistent 1° HPTH and negative noninvasive studies underwent selective venous sampling employing a rapid PTH assay in the interventional suite. ResultsVenous localization demonstrated an apparent PTH gradient in six of the seven patients. In three, a subtle gradient demonstrated in near real-time prompted additional sampling, which confirmed an unequivocal hormone gradient. In an additional case, the absence of a gradient on initial sampling prompted further sampling, which was positive. All of the patients were explored, and in five of the six patients with a positive PTH gradient, a parathyroid adenoma (mean weight 636 ± 196 mg) was resected from a location predicted by venous localization. In the sixth patient with a positive gradient, parathyroid tissue was not identified; however, there was a significant fall in the intraoperative PTH values, and immediate postoperative and follow-up laboratory data at 1 month are indicative of a cure. In the one patient with negative localization, abnormal parathyroid tissue could not be located during surgical exploration. ConclusionsThe rapid PTH assay is a major adjunct for obtaining informative venous localization in patients with persistent 1° HPTH. This information is extremely helpful to the surgeon in this challenging group of patients and resulted in a 100% cure rate when a venous gradient was demonstrated. The authors now employ this technique routinely in remedial patients with negative noninvasive imaging studies.

Interrelationships between maternal and cord prolactin, progesterone, estradiol, 13,14-dihydro-15-keto-prostaglandin F2α, and cord cortisol at delivery with respect to initiation of parturition

Estradiol, progesterone, prolactin, and 13,14-dihydro-15-keto prostaglandin F2alpha (PGFM) were measured in both maternal and cord venous blood obtained at the time of delivery in 24 maternal infant pairs evenly divided among six different physiologic groups. Progesterone and prolactin were significantly higher and estradiol was significantly lower in cord than in maternal blood. There were no significant differences between the groups for cortisol, estradiol, or progesterone in maternal or cord blood. A significant increase in prolactin was demonstrated in women receiving oxytocin for induction of labor. Both estradiol and PGFM were highly correlated between maternal and cord blood. PGFM was significantly higher in cesarean section patients in labor than in those not in labor in both the maternal and cord circulations. Among those delivered vaginally, PGFM tended to be higher in those in spontaneous labor than in those with induced labor. PGFM in induced labor was intermediate between spontaneous labor aptients delivered by cesarean section and those delivered vaginally. Duration of labor was negatively correlated with cord estradiol concentration. The physiologic significance of these findings is discussed.

Hypercalcitoninemia in infancy

Immunoreactive calcitonin (iCT) was measured in 19 infants with neonatal hypocalcemia. The infants had a variety of neonatal diseases and stresses. iCT levels were generally elevated to two to 20 times the adult values. Poor correlation existed between the infant age and the level of iCT or between iCT alone and the serum calcium. However, there was significant correlation between the serum calcium and the ratio of the iCT to infant age from conception, suggesting that both infant age and iCT levels in combination may be related to hypocalcemia. Also, it appears that a variety of neonatal stresses may be associated with increased sensitivity to the hypocalcemic effect of iCT, as well as increased levels of iCT.

Micro-electrolytic iodination of polypeptide hormones for radio-immunoassay.

A micro-electrolytic method for the radioactive iodination of polypeptide hormones is described (insulin, growth hormone, thyroid-stimulating hormone). A micro-cell was constructed permitting the labelling of minute amounts of hormones with 125I to high specific activity for use in radioimmunoassay. The purification of the labelled hormone was accomplished by Sephadex G-75 filtration and verified by high voltage chromatoelectrophoresis.

Binding of catechol derivatives to human serum proteins

Bindung der Katecholamine und deren Analogen durch Proteine der Humansera wurde untersucht. Durch Veränderung in der Alkylseitenkette wird die Bindungsfähigkeit der Katecholaminalogen geschwächt, doch nicht vernichtet. 3-O-methylierte Analogen verlieren ihre Bindungsfähigkeit und ist gegenüber Norepinephrin wirkungslos.

Triiodothyronine radioimmunoassay: A study of the interactions of T3 with anti-T3 antisera and with thyroxine binding globulin in the presence of ans (ammonium-8-anilinonaphthalene-1-sulfonate)

Abstract Two different antisera against triiodothyronine (T 3 ) have been studied in an assay system for T 3 in serum utilizing ammonium-8-anilino naphthalene-1-sulfonate (ANS) as an uncoupler of T 3 from thyroxine binding globulin (TBG). The effect of increasing amounts of ANS on the reaction between T 3 and anti-T 3 antisera and the effects of varying amounts of thyroxine binding globulin as well as thyroxine on the dynamics of the reactions were investigated. It is shown that in a radioimmunoassay system involving two binders (T 3 antibody and TBG) for a given ligand (T 3 ) it is important, in the evaluation of the antisera, to study its behavior in the presence of varying amounts and states of saturation of the other, naturally occurring binder (TBG).

Hypercalcitoninemia in pancreatitis--evidence for immunochemical heterogeneity.

Recently in our laboratory we have demonstrated increased immunoreactive calcitonin (iCT) levels in 4 patients with acute pancreatitis and hypocalcemia1. The present study consists of 17 additional patients in whom serial determinations for (iCT) were performed. Furthermore, with the use of 2 different antisera directed against human calcitonin we present evidence for immunochemical heterogeneity of this hormone in acute pancreatitis.

In vitro pituitary responsiveness to gonadotropin-releasing hormone (LH-RH) in intact and castrated male and female rats ☆

The in vitro response of pituitaries isolated from both normal and 18-21 day post-castration male and female intact rats to incremental doses of synthetic gonadotropin-releasing hormone (LH-RH) has been investigated. Intact male pituitaries released luteinizing hormone (LH) maximally at the smallest dose of LH-RH (0.1 ng/ml) whereas intact female pituitaries released LH in a dose-response fashion. FSH release from intact male pituitaries was considerably greater than that from intact female pituitaries. As with LH, intact male pituitaries appeared maximally stimulated at 0.1 ng/ml of LH-RH. Intact female pituitaries did not release FSH until a 10 ng/ml dose of LH-RH was used. Male and female castrate pituitaries were more susceptible to LH-RH-induced LH and FSH release than were their intact counterparts, although this was more pronounced with regard to LH release. In addition castrate male pituitaries were more sensitive to lower doses of LH-RH than were castrate female pituitaries, this being most pronounced regarding LH release. Castrate female pituitaries released less FSH at the 100 ng/ml dose than at the 10 ng/ml dose, possibly indicating inhibition at these higher doses. In addition, pituitary extraction and serum from normal and castrate male and female rats were examined for LH and FSH content. LH content of castrated rat pituitaries of both sexes was considerably greater than that of their intact counterparts, as expected. However, castrate male pituitaries contained significantly less FSH than intact male pituitaries, whereas the opposite was true for the female groups. Serum LH and FSH levels were increased in the castrate groups with no difference between sexes. Serum from intact males contained considerably more FSH than did the serum from intact females.

Gonadotropin-releasing hormone mediated luteinizing hormone and follicle stimulating hormone release from human pituitary tissue in vitro

Menschliche Hypophysen wurden mit und ohne LH-RH inkubiert und eine Freisetzung von LH und FSH in vitro gefunden, die sich durch Sexualsteroide hemmen lässt.

Comparative responsiveness of euthyroid and hypothyroid rat pituitary tissue to thyrotropin releasing hormone in vitro

Die Kapazität von Rattenhypophysen, auf eine TRH-Stimulation in vitro TSH auszuschütten, zeigt bei hohen TRH-Konzentrationen keine Differenz zwischen eu- und hypothyreoten Tieren, während eine niedrige TRH-Konzentration eine höhrere TSH-Ausschüttung bei Hypophysen euthyreoter Tiere verursacht.