Measurement of quality of recovery using the QoR-40: a quantitative systematic review.

BACKGROUND: Several rating scales have been developed to measure quality of recovery after surgery and anaesthesia, but the most extensively used is the QoR-40, a 40-item questionnaire that provides a global score and subscores across five dimensions: patient support, comfort, emotions, physical independence, and pain. It has been evaluated in a variety of settings, but its overall psychometric properties (validity, reliability, ease of use, and interpretation) and clinical utility are uncertain. METHODS: We undertook a quantitative systematic review of studies evaluating psychometric properties of the QoR-40. Data were combined in meta-analyses using random effects models. This resulted in a total sample of 3459 patients from 17 studies originating in nine countries. RESULTS: We confirmed content, construct, and convergent [pooled r=0.58, 95% confidence interval (CI): 0.51-0.65] validity. Reliability was confirmed by excellent intraclass correlation (pooled α=0.91, 95% CI: 0.88-0.93), test-retest reliability (pooled r=0.90, 95% CI: 0.86-0.92), and inter-rater reliability (intraclass correlation=0.86). The clinical utility of the QoR-40 instrument was supported by high patient recruitment into evaluation studies (97%), and an excellent completion and return rate (97%). The mean time to complete the QoR-40 was 5.1 (95% CI: 4.4-5.7) min. CONCLUSIONS: The QoR-40 is a widely used and extensively validated measure of quality of recovery. The QoR-40 is a suitable measure of postoperative quality of recovery in a range of clinical and research situations.

Deficient activity of hepatic acid lipase in cholesterol ester storage disease.

Absence of lysosomal acid lipase activity in the liver is described in cholesterol ester storage disease and Wolman's disease. This enzyme deficiency may result in the excess hepatic cholesterol ester found in both conditions. However, clinical, genetic, and histopathologic differences suggest that the two conditions are separate diseases not completely explained by deficient enzyme activity.

Two mathematical programming models of cheese manufacture.

The standardization problem faced by cheese makers is formulated as a nonlinear programming problem using the assumptions of the Van Slyke cheese yield formula. The objective function of the model is to minimize the net cost of producing a given quantity of cheese subject to a set of production constraints. An approximation of the standardization problem formulated as a linear programming problem is also presented. Two different approaches to finding a solution are provided. The model is implemented in Microsoft Excel and solved with the standard add-in solver available in that program. An example is provided to contrast the difference between the nonlinear programming and its linear approximation, and a second example is used to illustrate the yield implications of ultrafiltered milk protein products in Cheddar cheese production. Additionally, a method for pricing inputs using the sensitivity analysis generated by the solver is demonstrated.

Clinical and angiographic results of balloon-expandable intracoronary stents in right coronary artery stenoses.

Balloon-expandable stents were placed successfully in 35 (95%) of 37 patients whose right coronary artery lesion was believed to have a poor short- or long-term prognosis with conventional balloon angioplasty because of prior restenosis or adverse lesion morphology. Quantitative angiography showed a reduction in stenosis diameter from 83 +/- 14% to 42 +/- 14% after conventional balloon dilation, with a further reduction to -3 +/- 12% after stent placement (p less than 0.001). There were no acute stent thromboses, but one patient (with two stents and unstented distal disease) developed subacute thrombosis on day 8 after self-discontinuation of warfarin and was treated with thrombolytic therapy and redilation. Follow-up angiography was performed at 4 to 6 months in 25 patients, demonstrating restenosis (83 +/- 13%) in 4 (57%) of 7 patients with multiple stents, but only 3 (17%) of 18 patients with a single stent (p less than 0.05). Six of the seven in-stent restenotic lesions were subtotal (80 +/- 12%) and were subjected to repeat conventional balloon angioplasty (postdilation stenosis 13 +/- 21%). The 18 patients without restenosis had a maximal in-stent diameter stenosis of 29 +/- 15%, corresponding to a maximal focal neointimal thickness of 0.68 +/- 0.26 mm within the stented segment. These preliminary results suggest that the Schatz-Palmaz stent may be a useful adjunctive device in the performance of coronary angioplasty.

Neodymium neutron cross section measurements.

Neutron capture and transmission measurements were performed by the time-of-flight technique at the Rensselaer Polytechnic Institute LINAC using metallic neodymium samples. The capture measurements were made at the 25-m-long flight station with a 16-segment NaI(Tl) multiplicity detector, and the transmission measurements were performed at 15 and 25 m flight stations with a 6Li glass scintillation detector. After the data were collected and reduced, resonance parameters were determined by simultaneously fitting the transmission and capture data with the multilevel R-matrix Bayesian code SAMMY. The resonance parameters for all naturally occurring neodymium isotopes lie within the energy range of 1.0-500 eV. The resulting resonance parameters were used to calculate the capture resonance integral with this energy region and were compared to calculations obtained when using the resonance parameters from ENDF-B/VI. The RPI parameters gave a resonance integral value of 32 +/- 0.5 b that is approximately 7% lower than that obtained with the ENDF-B/VI parameters. The current measurements significantly reduce the statistical uncertainties on the resonance parameters when compared with previously published parameters.

Use of the reverse hemolytic plaque assay to study the regulation of anterior lobe adrenocorticotropin (ACTH) secretion by ACTH-releasing factor, arginine vasopressin, angiotensin II, and glucocorticoids.

A reverse hemolytic plaque assay (RHPA) for ACTH was developed to study the responses of anterior lobe corticotropes to secretagogues-CRF, arginine vasopressin (AVP), angiotensin II (A-II), or to a 6- to 24-h pretreatment with corticosterone. Tests showed that optimal plaque formation was obtained after 3-4 h with 1:100-1:200 anti ACTH-(25-39) and 1:20-1:50 complement. Under optimal basal conditions, 6.6% of pituitary cells from normal male rats formed plaques. The addition of 50-90 micrograms/ml ACTH to the anti-ACTH for 48 h before its use in the RHPA resulted in a decrease in percentage of ACTH plaques to levels not different from those obtained with preimmune serum, or when complement was omitted from the assay (0.9-1.3%). There was a gradual increase in percentage of ACTH plaques to 9.8% of the population after exposure to increasing doses of CRF (0.1-10 nM). These same high percentages of ACTH plaques could also be obtained by the addition of 1 nM AVP or A-II with the lowest doses of CRF (100-500 pM). Exposure to 1 nM AVP alone resulted in no significant increases in percentages above basal values. Average plaque areas were increased to maximal levels of three to four X basal with increasing doses of CRF. Finally, when cells were pretreated with 100 nM corticosterone for up to 24 h, the percentage of plaques formed under basal conditions was reduced by 60% (2.6%) and it did not increase after exposure to 1 nM CRF. The data from the RHPA correlate well with previous studies of corticotropes. Since ACTH cells normally represent 10% of the anterior lobe cell population, the RHPA shows that a subset of corticotropes (6.6%) is actively secreting under basal conditions tested in this study. The remaining 3% can be stimulated to form plaques by high doses of CRF (greater than 1 nM) or low doses of CRF (100 pM) and 1 nM AVP or A-II. Glucocorticoids reduce the percentage of ACTH plaques formed under basal or stimulated conditions and allow no CRF-stimulated increase in plaque area. This correlates with recent reports that show glucocorticoids inhibit proopiomelanocortin messenger RNA synthesis and lower the number of pituitary CRF receptors.

Synthesis and evaluation of 2-[(5-methylbenz-1-ox-4-azin-6-yl)imino]imidazoline, a potent, peripherally acting alpha 2 adrenoceptor agonist.

We have synthesized 2-[(5-methylbenz-1-ox-4-azin-6-yl)imidazoline, 3, a potent, peripherally acting alpha 2 adrenoceptor agonist. The agent is conveniently prepared in five steps from 2-amino-m-cresol. The agent has demonstrated good selectivity for alpha 2 adrenoceptors in binding and functional studies. When applied topically to eyes, the agent is efficacious for the reduction of intraocular pressure. The agent does not penetrate the blood-brain barrier and, as a consequence, does not lower blood pressure or induce sedation when administered topically or intravenously. We have determined the pKa and log P in water versus both octanol and dodecane of 3 and a set of related agents. The best physical parameter to explain its lack of central nervous system penetration appears to be log P measured in octanol versus water.

Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists.

A series of 2-(arylamino)imidazoles was synthesized and evaluated for activity at alpha 1- and alpha 2-adrenoceptors. This class of agents has been shown to have potent and selective agonist activity at the alpha 2-adrenoceptors. The most potent member of this class, 2-[(5-methyl-1,4-benzodioxan-6yl)amino]imidazole, proved efficacious for the reduction of intraocular pressure upon topical administration and for the reduction of blood pressure upon intravenous administration. During the course of our studies, we developed a new reagent that allowed rapid assembly of the target compounds. This reagent, N-(2,2-diethoxyethyl)carbodiimide, was convenient to prepare and was stable under low-temperature storage conditions.

Prostaglandin F2 alpha effects on intraocular pressure negatively correlate with FP-receptor stimulation.

According to the current working classification for prostanoid receptors, the prostaglandin F2 alpha-sensitive receptor (FP-receptor) may be identified by comparing the rank order of activity of prostaglandin F2 alpha (PGF2 alpha) and its analogues. In order to further understand the pharmacology of PGF2 alpha-induced ocular hypotension, the intraocular pressure response to PGF2 alpha and selected analogues was compared with their rank order of activity in typical FP-receptor preparations such as contraction of the cat iris sphincter and affinity for corporal luteal membrane binding sites. The rank order of potency for decreasing intraocular pressure was as follows: PGF2 alpha greater than PGF1 alpha greater than 16-phenoxytetranor PGF2 alpha greater than 17-phenyltrinor PGF2 alpha = fluprostenol (inactive). For cat iris sphincter contraction, the rank order of potency appears to be fluprostenol = 17-phenyltrinor PGF2 alpha greater than 16-phenoxytetranor PGF2 alpha = PGF2 alpha greater than PGF1 alpha. The rank order of potency for PGF2 alpha analogues in decreasing intraocular pressure appears to negatively correlate with the rank order for cat iris sphincter contraction and literature values for corporal luteal membrane binding. It is concluded that the ocular hypotensive effect of PGF2 alpha is not mediated by the FP-receptor.

Cardiac anaphylaxis: SRS-A potentiates and extends the effects of released histamine.

Immunologic immediate hypersensitivity reactions of the heart are characterized by tachycardia and arrhythmias caused by the release of endogenous cardiac histamine. The contribution of SRS-A to anaphylactic cardiac dysfunction was indirectly assessed by the use of the selective SRS-A receptor antagonist FPL 55712. In the presence of FPL 55712 the concentration-response curves for the chronotropic and arrhythmogenic effects of endogenous cardiac histamine were progressively shifted to the right as a function of the concentration of FPL 55712. Moreover, the duration of the positive chronotropic effect of endogenous cardiac histamine was shortened by FPL 55712. On the other hand, FPL 55712 failed to reduce the chronotropic and arrhythmogenic effects of exogenous histamine. Partially purified histamine-free SRS-A opbtained from rat peritoneum potentiated and greatly prolonged the positive chronotropic effect of exogenous histamine. Potentiation and prolongation were both blocked by FPL 55712. Thus, our results suggest that SRS-A sensitized the heart to the tachyarrhythmic effects of histamine.

Prejunctional adrenoceptor activity of N-0437: a relatively selective DA2 dopamine receptor agonist.

Prejunctional adrenoceptor activity of N-0437, 2[N-n-propyl-N-2-(thienylethyl-amino)-5-hydroxytetralin], was investigated by means of the cat nictitating membrane (CNM) preparation. Intra-arterial (i.a.) administration of N-0437 produced a dose-related inhibition (ED50 = 14 micrograms) of the CNM contractions elicited by electrical stimulation of pre- and postganglionic sympathetic nerves of the superior cervical ganglion. Pretreatment with domperidone i.a., a relatively selective DA2 receptor antagonist, markedly attenuated the CNM response to racemic N-0437 (ED50 = 6.7 x 10(2) micrograms). However, pretreatment with rauwolscine i.a., a relatively selective alpha 2-receptor antagonist, did not alter the CNM responses to racemic N-0437. Evaluation of the (R)-(+) and (S)-(-) enantiomers showed that only the (S)-(-) enantiomer was active in suppressing the contractions in the CNM preparation. These results demonstrate that N-0437 is a potent agonist for prejunctional DA2 dopamine receptors on peripheral sympathetic nerves in the CNM and that these peripheral DA2 receptors appear to be enantioselective.

Scanning electron microscopy of the urinary tract.

Scanning electron microscopy of the urinary tract. A scanning electron microscopic investigation of the luminal surface of the entire urinary tract of the Wistar rat was performed. This report defines criteria for identifying different segments of normal urinary tract on the basis of scanning electron microscopic observations of the epithelial surface. The study was undertaken to provide a reference for future studies of changes in urinary tract morphology resulting from injury or disease.

Aporphine derivatives affect ocular function in diverse ways.

The sympathetic nervous system has been implicated in the ocular effects of several classes of dopamine receptor agonists. Two agonists of the aporphine class, (-) N-propylnorapomorphine [-)NPA) and norapomorphine (NA), were evaluated for effects on intraocular pressure (IOP) and pupil diameter (PD) in cats and normal (NL) and sympathectomized (SX) rabbits and on contractions of the cat nictitating membrane (CNM). Topically administered (-)NPA produced a monophasic IOP drop in the ipsilateral eye and a biphasic (increase, decrease) IOP response in the contralateral eye of normal rabbits. Pupil diameter increased bilaterally. In NL cats, the ipsilateral IOP and PD response to (-)NPA was biphasic (increase, decrease) and the contralateral IOP response was monophasic (increase). (-)NPA produced an increase in spontaneous motor activity (SMA) in rabbits and cats. NA lowered IOP unilaterally in NL rabbits. In SX rabbit eyes, (-)NPA lowered IOP as much as in NL eyes but with less mydriasis. NA did not lower IOP in SX rabbit eyes. Both (-)NPA and NA inhibited contractions of the CNM elicited by electrical stimulation of the pre- and post-superior cervical ganglionic nerves. (-)NPA, but not NA, inhibited contractions elicited by exogenous norepinephrine. These results suggest that aporphine derivatives produced two diametrically opposed effects on ocular function; 1) a centrally mediated effect that enhanced noradrenergic activity to elicit mydriasis, SMA and ocular hypertension, and 2) a peripherally mediated effect to produce miosis and ocular hypotension.

Ocular effects of a relatively selective alpha 2 agonist (UK-14, 304-18) in cats, rabbits and monkeys.

UK-14, 304-18 (UK), a relatively selective alpha 2-agonist, was examined for its effects on intraocular pressure (IOP) and pupil diameter (PD) in rabbits, cats and monkeys and on noradrenergic function in the cat nictitating membrane (CNM) preparation. Topical, unilateral administration of UK (0.0005-0.5 mg) produced dose-dependent decreases in IOP and pupil size in normal, unanesthetized rabbits, cats and monkeys. The ocular hypotensive effect of UK in the ipsilateral eye was delayed relative to the contralateral eye in all three species; UK produced an initial transient ocular hypertension in rabbits which was abolished by surgical transection of three major extraocular muscles. Mean arterial blood pressure in rabbits was not affected by 0.005 mg UK topically. The ocular hypotensive and miotic effects of UK were attenuated in superior cervical ganglionectomized (SX) cats and rabbits. Intra-arterially administered UK (0.33, 1.0, 3.3 and 10 micrograms) produced dose-related systemic hypotension and inhibition of contractions of the CNM elicited by electrically stimulating the pre- and postganglionic sympathetic trunks in the urethane/chloralose anesthetized cat. This inhibition was reversed and prevented by 300 micrograms rauwolscine but not by 300 micrograms domperidone. UK also enhanced the contractile response of the CNM to injected norepinephrine (10 micrograms). UK suppressed ocular hypertension induced by water loading and IOP recovery rate following hypertonic saline infusion in rabbits suggesting that aqueous flow was inhibited. These results indicate that UK lowers IOP, in part, by suppressing sympathetic neuronal function which causes a reduction in aqueous flow.

Effects of ergoline derivatives on intraocular pressure and iris function in rabbits and monkeys.

The ergoline derivatives, bromocriptine, lergotrile and pergolide, are potent dopaminergic agonists. Topically administered doses of lergotrile and pergolide, ranging from 0.001 to 1% applied unilaterally, produced dose and time-related ocular hypotension in rabbits and monkeys. In contrast, bromocriptine produced moderate ocular hypotension in rabbits but not in monkeys. Lergotrile (1%) produced significant mydriasis in rabbits whereas pergolide (0.01 to 0.1%) produced a slight miosis. Lergotrile and pergolide were also effective in suppressing ocular hypertension induced by water loading in rabbits whereas bromocriptine was relatively ineffective. These data demonstrate that topically administered ergoline derivatives can: 1) lower intraocular pressure in rabbits and monkeys, 2) suppress ocular hypertension induced by water loading in rabbits and 3) alter iris function in rabbits, producing either mydriasis or miosis, presumably by activation of adrenoceptors.

An in vivo model for dissociating alpha 2-and DA2-adrenoceptor activity in an ocular adnexa: utility of the cat nictitating membrane preparation.

Recent reports from this laboratory indicate that dopamine (DA2) agonists can lower intraocular pressure (IOP) in rabbits, monkeys and rats. This communication suggests that the cat nictitating membrane (CNM) preparation is a useful model for localizing the site(s) and mechanism(s) of action of dopamine (DA2) agonists and that this model can be used to discriminate between alpha 2 and DA2 activity. This in vivo preparation consists of indirect (neuronal)- and direct (agonist)-induced activation of the CNM by: 1) pre- and postganglionic stimulation of sympathetic nerves and 2) injection of norepinephrine (NEPI) into the external carotid artery (i.a.). A variety of DA2-agonists (ergolines, azepines, aminotetralins, aporphines) can cause dose-dependent depression of neuronally mediated contractions with minimal effects on contractions elicited by NEPI i.a. Characteristically, DA2-agonists depressed contractions elicited by low frequency (2 & 4 Hz) stimulation more than high frequency (6 & 8 Hz) stimulation. For example, the inhibitory effects of an ergoline derivative LY141865 on neuronally mediated contractions of the CNM could be reversed (or prevented) by relatively selective DA2 antagonists, such as sulpiride and domperidone, but not by relatively selective alpha 2-antagonists, such as yohimbine and rauwolscine. Interestingly, alpha 2-adrenoceptor agonists, such as clonidine and xylazine, caused less depression of nerve-stimulated responses than did DA2-agonists at the same dose. This modest suppression by alpha 2-agonists could be inhibited by yohimbine but not by sulpiride or domperidone. These results with the CNM document the presence of DA2 receptors on sympathetic neurons innervating an ocular adnexa and demonstrate a model for dissociating DA2 from alpha 2 activity.

Forskolin suppresses sympathetic neuron function and causes ocular hypotension.

Recent reports suggest that forskolin can produce ocular hypotension in laboratory animals and man by enhancing formation of cyclic AMP. This proposed mechanism of action implies that forskolin lowers intraocular pressure (IOP) by activating adenylate cyclase at some postjunctional site. Intra-arterial (i.a.) injections of forskolin (10, 33, 100 & 333 micrograms) into the cat nictitating membrane (CNM) preparation produced dose-related inhibition of contractions elicited by electrical stimulation of pre-and postganglionic sympathetic neurons. Interestingly, contractions elicited by i.a. norepinephrine were inhibited less than neuronally mediated contractions. Topically applied forskolin (0.5 mg) to the eyes of unilaterally sympathectomized (SX) rabbits and normal rabbits elicited ocular hypotension in the innervated eyes only. Forskolin (0.5 mg, topically) suppressed the rise in IOP induced by water loading in normal rabbits but was significantly less effective in SX rabbits. These results suggest that forskolin lowered IOP in rabbits and suppressed contraction of the electrically-stimulated CNM, in part, by inhibiting sympathetic neuronal function.

Alteration in ocular function induced by phenylethylamine analogs of dopamine.

Dopamine (DA) and three methylated analogs (N-methyldopamine, NMDA; N, N- dimethyldopamine , DMDA ;N,N-di-n- propyldopamine , DPDA) were examined for effects on intraocular pressure (IOP) and pupil diameter (PD) in normal rabbits, sympathectomized (SX) rabbits and rabbits with transected extraocular muscles ( EOMX ) following topical administration. In normal rabbits, the predominant effect of DA, NMDA and DMDA was transient, unilateral ocular hypertension with minimal effects on PD. In contrast, DPDA produced bilateral ocular hypotension in normal rabbits. DA and NMDA did not produced ocular hypertension in EOMX rabbits indicative of an involvement of extraocular muscles in normal rabbits. In SX rabbits, NMDA produced mydriasis and exaggerated ocular hypertension followed by significant ocular hypotension; the ocular hypotensive phase was antagonized by timolol pretreatment. The ocular hypotensive activity of DPDA seen in normal rabbits was absent in SX rabbits suggestive of a neuronal site of action for DPDA. DPDA inhibited contraction of the cat nictitating membrane elicited by stimulation of pre- and postganglionic sympathetic nerves. This effect was antagonized by a dopamine (DA2) antagonist metoclopramide, indicative of a prejunctional site of action. NMDA and DA suppressed ocular hypertension induced by water loading. Only NMDA depressed the IOP recovery rate in response to infusion of hypertonic saline indicating suppression of aqueous humor formation. These results suggest that DA, NMDA and DMDA produce an initial ocular hypertension by contracting extraocular muscles. Timolol antagonized the ocular hypotensive effect of NMDA in SX rabbits indicating that this response is, in part, a function of beta-adrenoceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Ocular hypotensive action of ergoline derivatives in rabbits: effects of sympathectomy and domperidone pretreatment.

Ergot derivatives, such as bromocriptine, lergotrile and pergolide, are potent dopaminergic agonists in various biological systems. In topical doses ranging from 0.001 to 1% applied unilaterally, each agent produced dose-related ocular hypotension in normal rabbits. Utilizing an intraocular pressure (IOP) recovery rate method (aqueous formation index), each agent was observed to suppress the recovery rate of IOP in normal rabbits. Pretreatment with a prejunctional dopamine receptor antagonist (domperidone) inhibited the ocular hypotensive effect of bromocriptine and pergolide more than that of lergotrile. In rabbits with unilateral superior cervical ganglionectomies, IOP was lowered appreciably less by these compounds in the denervated eyes. These studies indicate that: a) lowering of IOP by these ergot derivatives is dependent, in part, on suppression of sympathetic neuronal activity; b) the most probable sites of action are DA2 receptors on sympathetic nerve endings or in sympathetic ganglia; c) ocular hypotension is produced, in part, by suppressing aqueous humor formation.

Ocular effects of a N,N-disubstituted 5-OH aminotetralin (N-0437): evidence for a dual mechanism of action.

The selective DA2 agonist, N-0437, produced an acute reduction in intraocular pressure (IOP) and pupil diameter (PD) when applied topically to the eyes of normal monkeys. Ocular hypotension and miosis were primarily unilateral in nature, dose-related and lasted 3 to 5 hours following drug instillation. In normal monkeys, 24 to 48 hours following drug administration, a secondary chronic (greater than 24 hrs) reduction in pressure was observed. Once-a-day topical administration of N-0437 (250 micrograms), to normal monkeys, for 4 days produced a chronic unilateral reduction in IOP that persisted for 18 days. Associated with this reduction in pressure on day 2 through 6 were miosis and ptosis of the treated eye. Although topical administration did not lower IOP in rabbits, intracameral injection of N-0437 significantly depressed IOP for 3 days when compared to control injected eyes. Evaluation of ocular sympathetic innervation in N-0437 treated rabbits indicated that these fibers were not functional. In rabbits, intracameral administration of the active (S,-) and inactive (R,+) enantiomer of N-0437 produced equivalent reductions in pressure. These data provide further support for the hypothesis that DA2 receptor agonists can produce acute reductions in IOP. In addition, N-0437 appears to have a second non-receptor mediated mechanism of action that produces a chronic reduction in IOP. This chronic reduction in pressure appears, in part, to result from an interruption of ocular sympathetic nerves function.