Konversion eines postoperativen Hypoparathyreoidismus in einen Hyperparathyreoidismus bei ektopem Nebenschilddrüsenadenom.

We present a patient with a history of thyroid cancer, presumably following radiochemotherapy of a childhood medulloblastoma, who developed a primary hyperparathyroidism 10 years after long-term postsurgical hypoparathyroidism. All established imaging modalities failed to detect the origin and only selective neck sampling could identify the suspected parathyroid adenoma causing hyperparathyroidism. This encourages the use of selective neck vein catheterization, particularly in patients with only slightly elevated parathyroid hormone-levels or suspected small ectopic adenoma.

Calcium transport proteins in active secretory zones: Na-Ca exchange isoforms and exchanger kinetic properties in chromaffin granules and plasma membranes.

We have found that Na-Ca exchange influences Ca(2+) efflux, signal decay, and the rate of secretion in chromaffin cells. We now report the presence of two distinct splicing variant isoforms of Na-Ca exchange proteins in bovine chromaffin cells and their transport properties in chromaffin granules and plasma membrane vesicles.

Clonogenic analysis reveals reserve stem cells in postnatal mammals: I. Pluripotent mesenchymal stem cells.

Clonal populations of lineage-uncommitted pluripotent mesenchymal stem cells have been identified in prenatal avians and rodents. These cells reside in the connective tissue matrices of many organs and tissues. They demonstrate extended capabilities for self-renewal and the ability to differentiate into multiple separate tissues within the mesodermal germ line. This study was designed to determine whether such cells are present in the connective tissues of postnatal mammals. This report describes a cell clone derived by isolation from postnatal rat connective tissues, cryopreservation, extended propagation, and serial dilution clonogenic analysis. In the undifferentiated state, this clone demonstrates a high nuclear-to-cytoplasmic ratio and extended capacity for self-renewal. Subsequent morphological, histochemical, and immunochemical analysis after the induction of differentiation revealed phenotypic markers characteristic of multiple cell types of mesodermal origin, such as skeletal muscle, smooth muscle, fat cells, cartilage, and bone. These results indicate that this clone consists of pluripotent mesenchymal stem cells. This report demonstrates that clonal populations of reserve stem cells are present in mammals after birth. Potential roles for such cells in the maintenance, repair, and regeneration of mesodermal tissues are discussed.

Assessment of laboratory quality in urine drug testing. A proficiency testing pilot study.

As part of a program to develop accreditation guidelines for urine drug testing laboratories, a pilot study for proficiency testing was conducted. Fifty civilian, commercial laboratories were included on a voluntary basis. Drug-free urine specimens were collected and either fortified with commonly abused drugs at concentrations comparable to casual use or submitted unfortified to participating laboratories as blanks. Samples were submitted on both an open and blind basis to the laboratories. Laboratory performance on open proficiency testing was comparable with that reported in existing proficiency testing programs. Blind proficiency testing produced less accurate results in terms of apparent false-negatives, but significant difficulties were evident in carrying out blind testing and in comparing its results with those of open testing. Specific problems have been identified to guide future programs.

Selectivity of serotonergic drugs for multiple brain serotonin receptors. Role of [3H]-4-bromo-2,5-dimethoxyphenylisopropylamine ([3H]DOB), a 5-HT2 agonist radioligand.

The affinities of putative serotonin receptor agonists and antagonists for 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT2 receptors were assayed using radioligand binding assays. The 5-HT1 sites were labeled with the agonist radioligands [3H]-8-hydroxy-2-(di-n-propylamino)-tetralin [3H]-8-OH-DPAT, [3H]-5-HT, and [3H]mesulergine. The 5-HT2 receptor was labeled with the antagonist radioligand [3H]ketanserin or the agonist radioligand [3H]-4-bromo-2,5-dimethoxyphenylisopropylamine ([3H]DOB). The apparent 5-HT1 receptor selectivity of agonist compounds was found to be 50- to 100-fold higher when the 5-HT2 receptor affinity was determined using the antagonist radioligand [3H]ketanserin than when the agonist radioligand [3H]DOB was used. Quipazine, a putative specific 5-HT2 agonist, appeared to be only 3-fold more potent at 5-HT2 than at 5-HT1A receptors when [3H]ketanserin was used as the 5-HT2 radioligand. When [3H]DOB was used as the 5-HT2 radioligand, quipazine was determined to be 100-fold more potent at 5-HT2 receptors than at 5-HT1A receptors. 1-(3-trifluoromethylphenyl)piperazine (TFMPP), a putative specific 5-HT1B receptor agonist was apparently 10-fold more potent at 5-HT1B receptors than at 5-HT2 receptors when [3H]ketanserin was used as the 5-HT2 radioligand. When [3H]DOB was used as the 5-HT2 radioligand, TFMPP was found to be equipotent at 5-HT1B and 5-HT2 receptors. Using the 5-HT2 antagonist radioligand [3H]ketanserin, a similar pattern of underestimating 5-HT2 receptor selectivity and/or overestimating 5-HT1A or 5-HT1B receptor selectivity was observed for a series of serotonin receptor agonists. Antagonist receptor selectivity was not affected significantly by the nature of the 5-HT2 receptor assay used. These data indicate that, by using an antagonist radioligand to label 5-HT2 receptors and agonist radioligands to label 5-HT1 receptors, the 5-HT1 receptor selectivity may be overestimated. This may be an especially severe problem in serotonin drug development as drugs that interact potently with 5-HT2 receptors have been reported to be psychoactive and/or hallucinogenic.

3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) labels a guanyl nucleotide-sensitive state of cortical 5-HT2 receptors.

3H-(+/-)-4-Bromo-2,5-dimethoxyphenylisopropylamine (3H-DOB), a putative agonist radioligand, was synthesized and used to label 5-HT2 receptors in a particulate fraction prepared from rat frontal cortex tissue homogenates. The specific binding (defined by the difference in 3H-DOB binding in the presence and absence of 10(-6) M cinanserin, a potent and specific 5-HT2 antagonist) displayed high affinity (KD = 4.1 X 10(-10) M) and saturability with a Bmax of 17.9 fmol/mg of protein. The distribution of specific 3H-DOB binding in nine brain regions correlated closely with the distribution of 3H-ketanserin (an antagonist radioligand)-labeled 5-HT2 receptors. Competition studies in frontal cortex homogenates using a variety of compounds revealed a distinct 5-HT2 receptor pharmacology. A series of 5-HT2 antagonists exhibited high affinities in competition studies for specific 3H-DOB binding. The absolute potencies of these antagonists as well as their order of potencies closely correlated with their potencies in competing for 3H-ketanserin-labeled brain 5-HT2 receptors. A series of 5-HT2 agonists also exhibited high affinities in competition studies for specific 3H-DOB binding. Although the order of potencies of these agonists was similar to their order in competing for 3H-ketanserin-labeled brain 5-HT2 receptors, the agonists displayed 10-100-fold higher affinities for the 3H-DOB-labeled sites than for the 3H-ketanserin-labeled sites. The level of specific 3H-DOB binding in the frontal cortex homogenates was approximately 5% of the levels of 3H-ketanserin-labeled 5-HT2 receptors (358 fmol/mg of protein). Taken together, these results indicate that 3H-DOB labels a subset of brain 5-HT2 receptors that has high affinity for agonists as well as antagonists); 3H-ketanserin appears to label both subsets of brain 5-HT2 receptors. Antagonists apparently do not discriminate between these two subsets of 5-HT2 receptors. 3H-DOB specific binding to 5-HT2 receptors was potently inhibited by guanosine 5'-(beta, gamma-imido)triphosphate and guanosine 5'-O-(3-thio)triphosphate (nonhydrolyzable derivatives of GTP) with IC50 values of 42 and 21 nM, respectively, whereas adenosine 5'-(beta, gamma-imido)triphosphate and adenosine 5'-O-(3-thio)triphosphate (nonhydrolyzable derivatives of ATP) had no effect. In summary, 3H-DOB specific binding displays the pharmacological characteristics of a 5-HT2 receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Plasma delta-9-tetrahydrocannabinol in pregnant sheep and fetus after inhalation of smoke from a marijuana cigarette.

Seven pregnant ewes were prepared with open-ended tracheal T tubes and with catheters in maternal femoral artery and in central circulation of fetus. Several days postoperatively, at 129-132 days gestation, ewes inhaled smoke from one marijuana cigarette containing 3.19% delta-9-tetrahydrocannabinol (delta-9-THC). Smoke was produced continuously in a hand-held chamber and delivered to the protruding arm of the tracheal tube. Samples of maternal and fetal blood were taken during the 8-10 minute smoking period and at intervals up to 24 hours. Delta-9-THC was detected in maternal plasma at 3 minutes and peaked at 10 minutes. Fetal plasma delta-9-THC reached detectable levels in 5 animals by 10 minutes. Maximum mean level was reached at 90 minutes and remained nearly constant until the fourth hour. Fetal delta-9-THC levels remained lower than maternal levels at all times. The terminal half-life of delta-9-THC in fetal and maternal plasma exceeded 10 hours.

Passive inhalation of marihuana smoke and urinary excretion of cannabinoids.

Three studies in which exposure to marihuana smoke was progressively increased were conducted. In each, four experienced marihuana users smoked marihuana cigarettes in the presence of two nonsmoking subjects. They were confined in a closed environment for 1 hr after the smoking began. All urine voided by the nonsmoking subjects was collected separately for 24 hr and analyzed for the presence of cannabinoids by the enzyme multiplied radioimmunoassay technique (EMIT) cannabinoid assay. Blood samples were drawn from one of the nonsmoking subjects in one of the studies, and delta 9-tetrahydrocannabinol (THC) plasma concentrations were determined by radioimmunoassay. The results obtained indicate that of 80 urine samples collected in the three studies, the drug levels in only two slightly exceeded the value of 20 ng/ml on the calibrator of the EMIT assay. Minute but detectable concentrations were present in the plasma of the one subject from whom blood samples were obtained. In this subject intravenous infusion of THC at the rate of 3.2 micrograms/min for 1 hr resulted in THC plasma concentrations identical to those during his passive inhalation of marihuana smoke.

Comparison of effects of marihuana cigarettes to three different potencies.

Marihuana cigarettes containing 1.32%, 1.97%, and 2.54% delta 9-tetrahydrocannabinol (THC) were smoked by six experienced marihuana users at weekly intervals in a double-blind cross-over design under laboratory conditions. Puff duration, number of puffs taken, duration of inhalation holding, interval between puffs, and duration of smoking were recorded for each cigarette smoked. The portion of each cigarette remaining after smoking was weighed and analyzed to determine THC content. Subjective ratings of the "high" achieved and the heart rate acceleration induced by smoking the marihuana were measured. The plasma concentrations of THC and of its principle metabolite, 11-nor-delta 9-THC-9-carboxylic acid (9-carboxy THC), were determined by radioimmunoassay of blood samples drawn at frequent intervals for 6 hr. The results indicate that, irrespective of the potency of the marihuana, the pattern of smoking was much the same. The magnitude of the subjective high, heart rate acceleration, THC, and 9-carboxy THC plasma concentrations were proportional to potency. This dose response was particularly clear between the 1.32% and the 2.54% cigarettes. Peak plasma concentrations of THC consistently occurred 7 to 8 min after initiation of smoking and declined thereafter despite continued smoking for another 6 to 10 min. Peak subjective high and peak heart rate acceleration occurred several minutes after the end of smoking and at a considerable interval after maximal THC plasma concentrations were reached.

Orthostatic hypotension after delta 9-tetrahydrocannabinol marihuana inhalation.

3 male glaucoma subjects experienced orthostatic hypotension within 10 min after completing 2% delta 9-THC ranging from 57 to 233 ng/ml were found 5 min after smoking. Peripheral venodilation appeared responsible for the precipitous decrease in systolic blood pressure in all 3 subjects. These orthostatic episodes which clinically simulated the typical 'faint' were characterized by the absence of tachycardia and their relief by assuming a reclining position. The postural hypotension occurred despite differences in inhalation technique, level of delta (9)-THC present in plasma, previous marihuana experience of body habitus.

Intravenous injection in man of 9 -tetrahydrocannabinol and 11-OH- 9 -tetrahydrocannabinol.

A microsuspension of Delta(9)-tetrahydrocannabinol and of its metabolic derivative 11-OH-Delta(9)-tetrahydrocannabinol has been prepared with 25 percent human serum albumin as the vehicle. Intravenous infusion of this preparation to humans indicates that both tetrahydrocannabinols are equally potent in producing the typical marihuana-like pschological and physiological effects.