Time course of effects of brief inhalations of nitrous oxide in normal volunteers

Nitrous oxide is commonly used (abused) recreationally by inhaling it in a bolus form (i.e. single or several breaths). The time course of the psychoactive effects of nitrous oxide, via this mode of inhalation, has not been adequately characterized and thus formed the basis for this study. Twelve healthy volunteers participated in four sessions, using a randomized, cross-over, placebo-controlled design. In each session one of the following four measures were assessed: self-reported strength of drug effects, mood, memory and psyckomotor performance. Within sessions, subjects were exposed to four different concentrations of nitrous oxide in a randomized fashion: 0% (oxygen-placebo), 40%, 60% and 80%. At each concentration, or “trial”, subjects took four deep breaths of the gas. Peak drug effects, as reported by our subjects, occurred within 30 seconds after the last inhalation of nitrous oxide, persisted for about a minute, and then gradually subsided to near-baseline levels by 5 minutes post-inhalation. Certain aspects of mood were briefly affected by nitrous oxide, generally in a dose-related fashion with increases in visual analog scale ratings of “anxious”, “stimulated”, “coasting (spaced out)”, “lightheaded”, “confused”, and “high”. Free recall of words that had been presented between 30 and 60 seconds post-inhalation was significantly reduced after 80% nitrous oxide, relative to oxygen-placebo. There was a trend towards psychomotor impairment (Concentration x time: p – 0.08), as measured by the Digit Symbol Substitution Test, with peak decrements in performance (about a minute after inhalation) being greater after 80% nitrous oxide than after 0% nitrous oxide. Our results suggest that there arc acute, albeit brief, adverse effects of inhaling bolus concentrations of nitrous oxide.     

NEUROMUSCULAR AND CARDIOVASCULAR EFFECTS OF DOXACURIUM IN CHILDERN ANAESTHETIZED WITH HALOTHANE

The neuromuscular and cardiovascular effects of doxacurium chloride(BW A938U) were evaluated in 27 children (2–12 yr) anaesthetizedwith 1% halothane and nitrous oxide in oxygen. In nine childrenthe incremental technique was used to establish a cumulativedose-response curve by train-of-four stimulation. The remainingchildren received either 30 or 50 µg kg^–1 of thedrug as a single bolus. The median ED₅₀ and ED ₉₅ of doxacuriumin children were 19 and 32 µg kg^–1, respectively.No clinically significant change in heart rate or arterial pressureoccurred. Following doxacurium 30 µg kg^–1 and 50µg kg^–1, recovery to 25% of control occurred in25 (SEM 6) and 44 (3) min, respectively. The recovery index(25–75% of control) was 27 (2) min. The duration of actionof doxacurium is similar to that of tubocurarine and dimethyl-tubocurarinein children. Compared with adults, children seem to requiremore doxacurium (µg kg^–1) to achieve a comparabledegree of neuromuscular depression, and they recover more rapidly. Presented in part at the American Society of AnesthesiologistsAnnual Meeting, October 1987, and the International AnesthesiaResearch Society Meeting, March 1988.     

Three-Generation Reproduction Study with Dioctyl Sodium Sulfosuccinate in Rats

Three-Generation Reproduction Study with Dioctyl Sodium Sulfosuccinatein Rats. MACKENZIE, K., HENWOOD, S., FOSTER, G., AKIN, F., DAViS,R., DEBAECKE, P., SISSON, G., AND MCKINNEY, G. (1990). Fundam.Appl Toxicol. 15, 53–62. Groups of 30 male and 30 femalerats (F0) were fed diets containing 0, 0. 1, 0.5, or 1.0% dioctylsodium sulfosuccinate (DSS) for 10 and 2 weeks, respectively.The F0 animals were then mated to produce an F1 litter. Groupsof 30 male and 30 female F1 animals were fed the same dose levelsfor at least 10 weeks postweaning, and the breeding programwas repeated to produce F2 animals. F3 animals were producedfrom F2 animals by the same procedure. The study was terminatedwith the F3 wean lings. Test diets were fed continuously throughoutthe study. All F0, F1, and F2 adults and F3 weanlings (one/sex/litter)were necropsied and given a macroscopic examination. There wereno effects on reproductive function for parental animals ofeither sex during any of the three generations in this study.At the highest dose level (1.0% DSS), body weights were lowerthan those of controls dunng the premating phase for males inall three generations and for F1 and F2 females. Body weightsfor F1 and F2 males and females in the 0.5% dose group werealso low during the premating phase. Pup weights on LactationDay 0 were significantly lower than those of controls only forthe high-dose group during the third generation. However, lowerpup weight gains in the mid-and high-dose groups resulted insignificantly lower pup weights on Day 21 for all three generations.Perinatal pup survival across three generations ranged from96 to 100% for the control and treated groups. Pup survivalranged from 95 to 100% for controls, from 98 to 100% for low-and mid-dose groups, and from 91 to 99% for the high-dose group.There were no treatment-related mortality and antemortem ormacroscopic observations. In summary, DSS administered in thediet to three successive generations of rats at levels of 0.5and 1.0% caused a reduction in body weights for parental malesin all generations and for F1 and F2 females, Pup weights atthe 0.5 and 1.0% dose levels were also lower than those of thecontrol in all three generations. However, the reduced bodyweights did not interfere with development of normal reproductiveperformance. DSS at levels up to 1.0% had no effects on thereproductive function of either sex in any generation and producedno treatment-related antemortem or macroscopic observations.     

THE TREATMENT OF SICCA FEATURES IN SJOGREN'S SYNDROME: A CLINICAL REVIEW

Patients with SS often suffer considerable distress due to siccasymptoms and the complications of mucosal dryness. Althoughthere are many topical treatments available, the literatureon their use is scant. This paper describes the treatments availableand suggests a rationale for the choice of product. KEY WORDS: Sjögren's syndrome, Keratoconjunctivitis sicca, Xerostomia, Treatment, Therapeutics, Guidelines     

Identification of Stage-Specific Changes in Protein Secretion by Isolated Seminiferous Tubules from the Rat Following Exposure to Either m-Dinitrobenzene or Nitrobenzene

The objective of this study was to identify effects of two knownSertoli cell toxicants on the secretion of proteins by seminiferoustubules (ST) isolated from adult rats at different stages ofthe spermatogenic cycle and cultured in vitro for 24 hr with[³⁵S]methionine Adult rats received a single oral dose of 50mg/kg metadinitrobenzene (m-DNB) or 300 mg/kg nitrobenzene (NB).Long lengths of ST at stages II–V, VI–VII or IX–XIIwere then isolated from control and treated rats at 1 or 3 dayspost-treatment; selection of stages was based on the stage specificityof the early (24–72 hr) adverse effects of m-DNB and NBon spermatogenesis in vivo. In addition, ST at the same stageswere isolated from untreated rats and cultured in the presenceor absence of m-DNB or NB (10^–4 M). Incorporation of [³⁵S]methionneinto secreted proteins was assessed and the pattern of proteinsecretion evaluated using two-dimensional sodium dodecyl sulfate-polyacrylamidegel electrophoresis (2-D SDS-PAGE). ST isolated from rats pretreated24 hr earlier with NB in vivo showed a significant decreasein the overall incorporation of [³⁵S]methionne into secretedproteins at stages VI–VIII and IX–XII, whereas STat stages II–V showed no such change; comparable proteinchanges were observed when 10^–4M NB was added in vitrofor 24 hr to ST isolated at the same stages from untreated rats.Similar results were obtained when ST protein secretion wasevaluated 72 hr after treatment with NB in vitro or after theaddition of NB in vitro to isolated ST from untreated rats for24 or 72 hr. In general, the results obtained after exposureto m-DNB were comparable to those observed for NB, with theexception that the incorporation of [³⁵S] into secreted proteinsby ST at stages II–V tended to be increased by m-DNB exposure.Analysis of ST-secreted proteins by 2-D SDS-PAGE identified6 "marker proteins" (MP) which showed major reproducible changesin secretion following exposure to either m-DNB or NB. In mostcases (MP–1, –2, –3, –5, and –6)their secretion was reduced markedly; two of these proteins(MP–2 and MP–3) are secreted almost exclusivelyat stages VI–VIII and correspond in molecular size andpI to two recently reported androgen-regulated proteins whichare thought to be products of the Sertoli cell. Exposure toeither NB or m-DNB also resulted in the appearance of one protein(MP–4) which was not secreted in detectable amounts byST from control animals. Previous data has shown that by 24hr after administration of either m-DNB or NB to rats thereis massive loss/degeneration of pachytene spermato cytes atstages VI–XII, whereas stages II–V of the spermatogeniccycle are not affected until 72 hr. The presently observed proteinchanges therefore either precede (stages II–V) or accompany(stages VI–XII) germ cell degeneration. This suggeststhat they may have potential use as markers of early toxicant-induceddamage and/or that changes in these proteins may mediate someof the adverse testicular effects of m-DNB and NB.     

Cyclic changes in composition and volume of the breast during the menstrual cycle, measured by magnetic resonance imaging

Summary. The volumes and spin-lattice (T₁) relaxation times of breast tissues and parenchymal water content were measured non-invasively by magnetic resonance imaging (MRI) in eight healthy women during four to eight consecutive menstrual cycles. Total breast volume, and parenchymal volume, T₁ relaxation time and water content were lowest between days 6 and 15. Between days 16 and 28, parenchymal volume, T₁ relaxation time and water content rose sharply by 38·9%, 15·1% and 24·5%, respectively, and peaked after day 25. Within 5 days of the onset of menses, parenchymal volume fell sharply by 30·3%, while water content declined by 17·5%. Rising parenchymal volume in the second half of the menstrual cycle is not solely due to increased tissue water content and provides in vivo evidence for both growth and increased tissue fluid at this time.     

Protected Carotid Stenting in High‐Risk Patients: Results of the SpideRX Arm of the Carotid Revascularization with ev3 Arterial Technology Evolution Trial

Purpose: A prospective nonrandomized multicenter registry of 160 patients with severe carotid stenosis and high‐risk features for carotid endarterectomy was conducted during the 3‐month period from March to May 2005. Methods: Carotid artery stenting (CAS) was performed with the SpideRX? Embolic Protection System (ev3, Inc., Plymouth, MN, USA) as part of an investigational device exemption from the Food and Drug Administration. Results: The primary end‐point of major adverse cardiac and cerebrovascular events at 30 days after CAS was observed in nine patients (5.6%), including death in four patients (2.5%), nonfatal stroke in five patients (3.1%), and nonfatal myocardial infarction in one patient (0.6%). A secondary end‐point of technical success (defined as successful deployment of all devices, filter retrieval, and final diameter stenosis <50%) was achieved in 156 of 160 patients (97.5%). The only independent predictor of death or stroke at 30 days was baseline stenosis severity (P < 0.05). Conclusion: CAS with distal embolic protection using the SpideRX? Embolic Protection System is a reasonable alternative for revascularization of some high‐risk patients with severe carotid stenosis. (J Interven Cardiol 2010;23:491–498)