Sensible approaches to avoid needle stick accidents in nuclear medicine

OBJECTIVE: Needle sticks are a continuous concern in the health care environment because of the prevalence of bloodborne pathogens in today's society. Radioactive contamination is another concern with needle sticks during nuclear medicine and nuclear pharmacy procedures. In our institution, substantial efforts have been made to prevent needle sticks, but they still occur occasionally. The purpose of this project was to analyze different practices and products to determine the best protocol in an effort to avoid further needle sticks. METHODS: The nuclear medicine technologists were surveyed to determine how many needle sticks have occurred and the situation behind each occurrence. Using our initial survey, the circumstances involved in each incident were reviewed, suggestions considered, and various means of protection analyzed. Five options were presented in a second survey. RESULTS: The results of the second survey showed that technologists favored the newly designed needle-capping blocks for preventing needle sticks in their daily routine procedures. CONCLUSION: The newly designed needle-capping block is best suited for both nuclear medicine and nuclear pharmacy laboratories. We will continue to monitor the effectiveness of this new approach in preventing needle sticks.     

Corneal astigmatism as a special complication after lid-loading in patients with lagophthalmos Hornhautastigmatismus als besondere Komplikation*

Lid-loading with precious metals, described by Illig in 1958, has become increasingly important. Because of its good functional and cosmetic results this method is superior to tarsorrhaphy. Furthermore, lid-loading can be combined with additional surgical techniques to achieve more dynamic lid-closure. In a prospective study we examined the results after lid-loading and discuss postoperative changes of the cornea.     

Resiniferatoxin-type phorboid vanilloids display capsaicin-like selectivity at native vanilloid receptors on rat DRG neurons and at the cloned vanilloid receptor VR1.

1 Although the cloned rat vanilloid receptor VR1 appears to account for both receptor binding and calcium uptake, the identification of vanilloids selective for one or the other response is of importance because these ligands may induce distinct patterns of biological activities. 2 Phorbol 12,13-didecanoate 20-homovanillate (PDDHV) evoked 45Ca(2+)-uptake by rat dorsal root ganglion neurons (expressing native vanilloid receptors) in culture with an EC50 of 70 nM but inhibited [3H]-resiniferatoxin (RTX) binding to rat dorsal root ganglion membranes with a much lower potency (Ki>10,000 nM). This difference in potencies represents a more than 100 fold selectivity for capsaicin-type pharmacology. 3 45Ca2+ influx by PDDHV was fully inhibited by the competitive vanilloid receptor antagonist capsazepine, consistent with the calcium uptake occurring via vanilloid receptors. 4 PDDHV induced calcium mobilization in CHO cells transfected with the cloned rat vanilloid receptor VR1 with an EC50 of 125 nM and inhibited [3H]-RTX binding to these cells with an estimated Ki of 10,000 nM. By contrast, PDDHV failed to evoke a measurable calcium response in non-transfected CHO cells, confirming its action through VR1. 5 We conclude that PDDHV is two orders of magnitude more potent for inducing calcium uptake than for inhibiting RTX binding at vanilloid receptors, making this novel vanilloid a ligand selective for capsaicin-type pharmacology. These results emphasize the importance of monitoring multiple endpoints for evaluation of vanilloid receptor structure-activity relations. Furthermore, PDDHV now provides a tool to explore the biological correlates of capsaicin-type vanilloid pharmacology.     

Acute hemodynamic and renal effects of adrenomedullin in rats with aortocaval shunt

Heart failure is characterized by increased vascular resistance and water retention. Adrenomedullin is a peptide hormone with vasodilating and diuretic properties whose efficacy in heart failure has not been well established. We used an aortocaval shunt model of moderate heart failure in rats and infused increasing doses of adrenomedullin, both as bolus injections and 20-min infusions. In controls, a clear dose-dependent 4.8+/-1.0 to 13.6+/-2.3 mm Hg decrease in arterial blood pressure was observed after injection of 1 microg to 30 microg of adrenomedullin. In rats with aortocaval shunt, the hypotensive responses were significantly diminished. The urine flow rate, which was diminished at baseline in rats with aortocaval shunt, was increased and normalized by adrenomedullin administration. The glomerular filtration rate increased after infusion of adrenomedullin (0.5 microg/kg min(-1)) from 2.37+/-0.25 to 3.47+/-0.43 ml/min (P<0.01) in controls and from 1.79+/-0.33 to 2.58+/-0.49 (P<0.05) in rats with aortocaval shunt. Similarly, renal blood flow was significantly increased by adrenomedullin in both groups. Our results indicate a beneficial effect of adrenomedullin on renal function in rats with aortocaval shunt. These data suggest that adrenomedullin might be of potential therapeutic value in heart failure, without inordinately decreasing blood pressure.     

The influence of penetrating keratoplasty and cyclosporin A therapy on MHC class II (Ia)-positive cells in the rat iris and choroid

Background: The presence of Ia-positive cells (MHC class II equivalent) has been previously reported in the iris and choroid of various species. They have been reported to have both round and dendritic morphologies; the latter may represent classic dendritic cells, potent antigen-presenting cells (APCs). It is possible that the dendritic-like cells play a important role in (auto)immune processes of uveal and other ocular tissues. Using the flat or whole mount technique, the distribution of Ia-positive cells in the rat iris and choroid was investigated following penetrating Keratoplasty (PKP) and following treatment with cyclosporin A (CsA). Methods: Lewis (LW) rats received corneal buttons from Lewis-Brown Norway (LW-BN) donors and were randomly assigned to the following groups: (i) operated, untreated (n=24); (ii) operated, CsA-treated (10 mg/kg i.m.;n=22). Controls were groups (iii) normal LW rats (n=13); (iv) unopcrated, CsA-treated (16 days' treatment;n=8); (v) anterior perforation of the anterior chamber (n=3); (vi) eight corneal sutures only (n=4); (vii) syngeneic operated (LW to LW;n=4). Animals of groups (i) and (ii) were killed on the 5th, 9th and 13th postoperative days and on appearance of the corneal rejection (group i, day 13; group ii, day 16). Both eyes were enucleated, immediately fixed, and iris-choroid flat mounts were examined for Ia-positive cells using APAAP immunohistochemistry. Results: In the normal Lewis rat iris, scattered Ia-positive cells of both nondendritic and dendritic morphology were observed. CsA treatment in the unoperated rat did not result in a significant decrease in the percentage of dendritic cells in the iris or choroid. Anterior chamber perforation, the placement of sutures in the cornea and syngeneic PKP resulted in a moderate increase in iris Ia-positive cells. Allogeneic transplantation resulted in a large increase in both types of Ia-positive cells, particularly on day 13 with corneal rejection. In group ii, an initial decrease in Ia-positive cells until day 13 was observed; upon rejection (day 16), the histological picture was similar to that of untreated animals. Alterations in the operated choroid were also apparent following CsA treatment. Conclusion: Corneal transplantation in the Lewis rat results in an increase in Ia-positive cells in the iris; CsA therapy can delay but not prevent this reaction. Changes in choroidal Ia-positive cells following PKP were not apparent, their numbers being affected only by CsA treatment following grafting.     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

• 1 Autoradiographic binding studies have shown that the AT₁ receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT₁ receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord.
• 2 While there are differences between species, AT₂ receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat.
• 3 Circulating AngII acts on AT₁ receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking.
• 4 Centrally administered AngII may act on AT₁ receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion.
• 5 Recent evidence shows that centrally administered AT₁ antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses.
• 6 Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT₁ receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.

     

Actigraphically recorded motor activity and immobility across sleep cycles and stages in healthy male subjects

The aim of this study was to compare the extent to which activity and immobility measures are related to sleep stages and sleep cycles in order to improve the informative value of actigraphic assessment of sleep. We therefore performed simultaneous ambulatory polysomnography and wrist-activity monitoring (AM) in 14 healthy male subjects without sleep complaints. In this context, a simple method for transforming raw motor activity data into a time-series reflecting onset and duration of activity and immobility clusters is introduced. Our results demonstrate that nocturnal AM measures were significantly affected by sleep stage. Low activity levels and particularly prolonged episodes of uninterrupted immobility were associated with increasing sleep depth. On the other hand, high activity levels and prolonged episodes of activity were related to intermittent wakefulness during sleep. Our results suggest that measures reflecting the occurrence and duration of activity and immobility clusters provide a better approach in studying the relationship between activity/immobility and sleep stages. Except for the duration of uninterrupted immobility episodes, which showed a significant decrease in the fourth cycle, none of the AM measures showed a significant cycle-to-cycle variation. Consequently, mean nocturnal motor activity measures provide an accurate reflection of the total sleep period. However, none of the AM-derived measures seems useful in evaluating the cycle structure during sleep.     

Synthesis and biological activity of new HMG-CoA reductase inhibitors. 3. Lactones of 6-phenoxy-3,5-dihydroxyhexanoic acids.

A group of 43 optically active sodium carboxylates (11a-qq and the corresponding lactones 4 were prepared from respective phenols 8 according to Schemes I-III. Phenols 8 were synthesized from commercially available compounds according to Schemes IV-IX. A number of these HMG-CoA reductase inhibitors 11 exceeded mevinolin's activity in vitro (Tables II and III). Selected lactones 4 effectively inhibited hepatic "de novo" cholesterol synthesis in rats in vivo (Table IV). After po administration to rabbits, 4ff(11ff), 4hh, and notably 11jj reduced plasma cholesterol levels more potently than mevinolin (Table V). Whereas 4ff(11ff) displayed the slight superiority expected according to in vitro data, 4hh and 11jj were considerably more potent than expected. Each of these compounds had only moderate activity after po administration to dogs (Table VI). Compound di-11ii, a hybrid of the structural elements of probucol and HMG-CoA reductase inhibitors, after po administration to rats decreased serum lipoproteins and increased HDL/LDL ratio better than probucol (Table VII). HMG-CoA reductase inhibitor 11ll and phenolic building blocks 8, notably 8jj and 8kk, inhibited LDL oxidation in vitro (Table VIII). Chemical structure-activity relationships (Table IX) and the pharmacological profile of phenoxy-type inhibitors 11 diverged from those of known HMG-CoA reductase inhibitors.     

The pharmacokinetics and pharmacodynamics of lisuride in healthy volunteers after intravenous,intramuscular, and subcutaneous injection

Summary The plasma concentration of lisuride and prolactin have been measured in twelve healthy male volunteers after IV, IM or SC injection of 25 g lisuride hydrogen maleate as an aqueous solution.After IV administration the plasma lisuride fell in two phases with half-lives of 14 min and 1.5 h. Total clearance was 13 ml·min^–1·kg^–1. After IM and SC injection the plasma concentrations peaked at 12 to 15 min and the profiles were similar to that found after IV administration. The systemic availabilities were 90% and 94%, respectively. Prolactin concentrations were reduced by a maximum of 60% relative to the normal circadian rhythm after all three routes of administration.The treatments were well tolerated, the only adverse reactions reported by some of the volunteers being mild, transient dizziness, tiredness, and nausea.