Determinants of women's dissatisfaction with anaesthesia care in labour and delivery.

Patient-centred care and factors associated with patient satisfaction with anaesthesia have been widely studied. However, the most important considerations in the setting of obstetric anaesthesia are uncertain. Identification of, and addressing, factors that contribute to patient dissatisfaction may improve quality of care. We sought to identify factors associated with < 100% satisfaction with obstetric anaesthesia care. At total of 4297 women treated by anaesthetists provided satisfaction data 24 h after vaginal and 48 h after caesarean delivery. As 78% of women were 100% satisfied, we studied factors associated with the dichotomous variable, 100% satisfied vs. < 100% satisfied. We evaluated patient characteristics and peripartum factors using multivariable sequential logistic regression. The following factors were strongly associated with maternal dissatisfaction after vaginal delivery: pain intensity during the first stage of labour; pain intensity during the second stage of labour; postpartum pain intensity; delay > 15 min in providing epidural analgesia and postpartum headache (all p < 0.0001). Pruritus (p = 0.005) also contributed to dissatisfaction after vaginal delivery, whereas non-Hispanic ethnicity was negatively associated with dissatisfaction (p = 0.01). After caesarean delivery, the intensity of postpartum pain (p < 0.0001), headache (p = 0.001) and pruritus (p = 0.001) were linked to dissatisfaction. Hispanic ethnicity also had a negative relationship with dissatisfaction after caesarean delivery (p = 0.005). Thus, inadequate or delayed analgesia and treatment-related side-effects are associated with maternal dissatisfaction with obstetric anaesthesia care. Development of protocols to facilitate identification of ineffective analgesia and provide an appropriate balance between efficacy and side-effects, are important goals to optimise maternal satisfaction.

Prediction of outliers in pain, analgesia requirement, and recovery of function after childbirth: a prospective observational cohort study.

BACKGROUND: Prediction models to identify parturients who experience protracted pain, prolonged opioid use, and delayed self-assessed functional recovery are currently inadequate. METHODS: For this study, 213 nulliparous women who planned vaginal delivery were enrolled and assessed daily until they completed three outcomes: (1) pain resolution; (2) opioid cessation; and (3) self-assessed functional recovery to predelivery level. The primary composite endpoint, 'pain and opioid-free functional recovery' was the time required to reach all three endpoints. The subjects were divided into two categories (the worst (longest time) 20% and remaining 80%) for reaching the primary composite endpoint, and each individual component. Prediction models for prolonged recovery were constructed using multivariate logistic regression with demographic, obstetric, psychological, and health-related quality of life characteristics as candidate predictors. RESULTS: Labour induction (vs spontaneous labour onset) predicted the worst 20% for the primary composite endpoint in the final multivariate model. Labour induction and higher postpartum day 1 numerical rating score for pain were predictors for being in the worst 20% for both functional recovery and pain burden. Labour type, delivery type, Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety score, RAND 36 Item Health Survey 1.0 (SF-36) physical health composite score, and postpartum breastfeeding success were predictive of delayed opioid cessation. CONCLUSIONS: Labour induction and elevated numerical rating score for pain are predictive of poor recovery after childbirth. Further research is necessary to determine whether modification would benefit mothers at risk for poor recovery.

Patient choice compared with no choice of intrathecal morphine dose for caesarean analgesia: a randomized clinical trial.

BACKGROUND: The study aimed to determine whether a patient's choice for their intrathecal morphine (ITM) dose reflects their opioid requirements and pain after caesarean delivery and if giving women a choice of ITM dose would reduce opioid use and improve pain scores compared with women who did not have a choice. METHODS: A total of 120 women undergoing caesarean delivery with spinal anaesthesia were enrolled in this randomized, double-blind study. Patients were randomly assigned to a choice of 100 or 200 µg ITM or no choice. The study involved deception, such that all participants were still randomly assigned 100 or 200 µg ITM regardless of choice. Rescue opioid use over the 48-h study period was the primary outcome measure. Pain at rest and movement and side effect (pruritus, nausea, and vomiting) data were collected 3, 6, 12, 24, 36 and 48 h postoperatively. Data are presented as median [95% confidence interval (CI)]. RESULTS: Women who requested the larger ITM dose required more supplemental opioid [median 0.8 (95% CI 0.4-1.3)] mg morphine equivalents at each assessment interval; P < 0.001] and reported more pain with movement [median 1.2 (95% CI 0.5-1.9)] verbal numerical rating score of 0-10 points] than patients who requested the smaller ITM dose ( P = 0.0008), regardless of the ITM dose given. There was no difference in opioid use whether the patient was offered a perceived choice or not. CONCLUSIONS: Women who were given a choice and chose the larger ITM dose correctly anticipated a greater postoperative opioid requirement and more pain compared with women who chose the smaller dose. Simply being offered a choice did not impact opioid use or pain scores after caesarean delivery. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01425762).

Evaluation of fixed and variable hospital costs due to Clostridium difficile infection: institutional incentives and directions for future research.

BACKGROUND: Economic analysis of Clostridium difficile infection (CDI) should consider the incentives facing institutional decision-makers. To avoid overstating the financial benefits of infection prevention, fixed and variable costs should be distinguished. AIM: To quantify CDI fixed and variable costs in a tertiary referral hospital during August 2015. METHODS: A micro-costing analysis estimated CDI costs per patient, including the additional costs of a CDI outbreak. Resource use was quantified after review of patient charts, pharmacy data, administrative resource input, and records of salary and cleaning/decontamination expenditure. FINDINGS: The incremental cost of CDI was €75,680 (mean: €5,820 per patient) with key cost drivers being cleaning, pharmaceuticals, and length of stay (LOS). Additional LOS ranged from 1.75 to 22.55 days. For seven patients involved in a CDI outbreak, excluding the value of the 58 lost bed-days (€34,585); costs were 30% higher (€7,589 per patient). Therefore, total spending on CDI was €88,062 (mean: €6,773 across all patients). Potential savings from variable costs were €1,026 (17%) or €1,768 (26%) if outbreak costs were included. Investment in an antimicrobial pharmacist would require 47 CDI cases to be prevented annually. Prevention of 5%, 10% and 20% CDI would reduce attributable costs by €4,403, €8,806 and €17,612. Increasing the incremental LOS attributable to CDI to seven days per patient would have increased costs to €7,478 or €8,431 (if outbreak costs were included). CONCLUSION: As much CDI costs are fixed, potential savings from infection prevention are limited. Future analysis must consider more effectively this distinction and its impact on institutional decision-making.

Unexpected diversity of bioluminescence in planktonic worms.

The vast majority of pelagic bioluminescent organisms emit a blue light with emission maxima (λmax ) ranging from 450 to 490 nm. Among the known outliers, the tomopterids (Annelida: Polychaeta) are usually described as yellow-emitters (λmax  = 565-570 nm) for which bioluminescence functions as a specific recognition signal. Here, we report the first data regarding the colours emitted by four different tomopterid species, Tomopteris pacifica, T. carpenteri, T. septentrionalis and T. planktonis. Surprisingly, T. planktonis is a blue-emitter (λmax  = 450 nm). Our pharmacological results on T. planktonis support cholinergic control, as recently demonstrated in the yellow-emitter, T. helgolandica. Moreover, as revealed by epifluorescence microscopy, the light seems to be produced in both species from the same yellow-pigmented parapodial glands. Despite these similarities, tomopterids express an unexpected diversity of bioluminescent colour patterns. This leads us to reassess the ecological value of bioluminescence within this group.

Free-floating epithelial micro-tissue arrays: a low cost and versatile technique.

Three-dimensional (3D) tissue models are invaluable tools that can closely reflect the in vivo physiological environment. However, they are usually difficult to develop, have a low throughput and are often costly; limiting their utility to most laboratories. The recent availability of inexpensive additive manufacturing printers and open source 3D design software offers us the possibility to easily create affordable 3D cell culture platforms. To demonstrate this, we established a simple, inexpensive and robust method for producing arrays of free-floating epithelial micro-tissues. Using a combination of 3D computer aided design and 3D printing, hydrogel micro-moulding and collagen cell encapsulation we engineered microenvironments that consistently direct the growth of micro-tissue arrays. We described the adaptability of this technique by testing several immortalised epithelial cell lines (MDCK, A549, Caco-2) and by generating branching morphology and micron to millimetre scaled micro-tissues. We established by fluorescence and electron microscopy that micro-tissues are polarised, have cell type specific differentiated phenotypes and regain native in vivo tissue qualities. Finally, using Salmonella typhimurium we show micro-tissues display a more physiologically relevant infection response compared to epithelial monolayers grown on permeable filter supports. In summary, we have developed a robust and adaptable technique for producing arrays of epithelial micro-tissues. This in vitro model has the potential to be a valuable tool for studying epithelial cell and tissue function/architecture in a physiologically relevant context.

Oral choline supplementation for postoperative pain.

BACKGROUND: Activation of nicotinic receptors with nicotine has been shown to reduce post-surgical pain in clinical and preclinical studies. Choline is a selective agonist at α7-type nicotinic receptors that does not have addictive or sympathetic activating properties. It is anti-nociceptive in animal studies. We conducted a double-blind randomized trial of oral choline supplementation with lecithin to aid in the treatment of pain after gynaecological surgery. METHODS: Sixty women having open gynaecological surgery were randomly assigned to receive 20 g of lecithin before surgery or placebo. Plasma choline concentration and tumour necrosis factor (TNF) were measured. Pain report was the primary outcome measure. RESULTS: We achieved a small but statistically significant increase in choline after surgery with oral supplementation. Plasma TNF was not decreased and pain report was not different between groups at rest or with movement. There were no adverse effects of treatment. CONCLUSIONS: Oral supplementation with lecithin during the perioperative period resulted in very slow absorption and thus only a small increase in plasma choline was achieved. This concentration was inadequate to reduce TNF as has been shown in other studies. The absence of an anti-inflammatory effect was likely related to our failure to demonstrate efficacy in pain reduction.

Anaesthetic considerations for non-obstetric surgery during pregnancy.

Surgery during pregnancy is complicated by the need to balance the requirements of two patients. Under usual circumstances, surgery is only conducted during pregnancy when it is absolutely necessary for the wellbeing of the mother, fetus, or both. Even so, the outcome is generally favourable for both the mother and the fetus. All general anaesthetic drugs cross the placenta and there is no optimal general anaesthetic technique. Neither is there convincing evidence that any particular anaesthetic drug is toxic in humans. There is weak evidence that nitrous oxide should be avoided in early pregnancy due to a potential association with pregnancy loss with high exposure. There is evidence in animal models that many general anaesthetic techniques cause inappropriate neuronal apoptosis and behavioural deficits in later life. It is not known whether these considerations affect the human fetus but studies are underway. Given the general considerations of avoiding fetal exposure to unnecessary medication and potential protection of the maternal airway, regional anaesthesia is usually preferred in pregnancy when it is practical for the medical and surgical condition. When surgery is indicated during pregnancy maintenance of maternal oxygenation, perfusion and homeostasis with the least extensive anaesthetic that is practical will assure the best outcome for the fetus.

Antinociceptive and anti-inflammatory effects of choline in a mouse model of postoperative pain.

BACKGROUND: Choline is a dietary supplement that activates alpha7 nicotinic receptors. alpha7 nicotinic activation reduces cytokine production by macrophages and has antinociceptive activity in inflammatory pain models. We hypothesized that systemic administration of choline would reduce the inflammatory response from macrophages and have antinociceptive efficacy in a murine model of postoperative pain. METHODS: We studied the response of wild-type and alpha7 nicotinic knockout mice to heat and punctate pressure after a model surgical procedure. We investigated the effect of genotype and choline treatment on alpha-bungarotoxin binding to, and their production of tumour necrosis factor (TNF) from, macrophages. RESULTS: Choline provided moderate antinociception. The ED(50) for choline inhibition of heat-induced allodynia was 1.7 mg kg(-1) h(-1). The ED(50) for punctate pressure threshold was 4.7 mg kg(-1) h(-1) choline. alpha7 nicotinic knockout mice had no change in hypersensitivity to heat or pressure and were significantly different from littermate controls when treated with choline 5 mg kg(-1) h(-1) (P<0.05, 0.01). Choline 100 mM reduced binding of alpha-bungarotoxin to macrophages by 72% and decreased their release of TNF by up to 51 (sd 11)%. There was no difference by genotype in the inhibition of TNF release by choline. CONCLUSIONS: Systemic choline is a moderately effective analgesic via activation of alpha7 nicotinic acetylcholine receptors. The antinocicepive effect may not be mediated by a reduction of TNF pathway cytokine release from macrophages. Although choline at millimolar concentrations clearly inhibits the release of TNF, this effect is not alpha7 subunit-dependent and occurs at concentrations likely higher than reached systemically in vivo.

Accuracy of Arabic versions of three asthma symptoms questionnaires against the clinical diagnosis of asthma.

Validation studies of asthma symptom questionnaires against provocation tests of bronchial hyperresponsiveness have shown comparable performances of written and video taped questionnaires. This study aimed to determine the test characteristics of Arabic versions of two written and one video taped questionnaires when compared to the clinical diagnosis of asthma made by two respiratory physicians. The written International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire had higher sensitivities and greater accuracy than the other two questionnaires. Comparisons between corresponding questions and scenes in the ISAAC questionnaires in general revealed no significant differences in performance. The ISAAC written questionnaire had test characteristics consistent with its potential use as a screening instrument for asthma in this population of children.

Role of microglia in inflammation-mediated degeneration of dopaminergic neurons: neuroprotective effect of interleukin 10.

Inflammation in the brain has been recognized to play an increasingly important role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease. Inflammation-mediated neurodegeneration involves activation of the brain's resident immune cells, the microglia, which produce proinflammatory and neurotoxic factors including cytokines, reactive oxygen species (ROS), nitric oxide, and eicosanoids that directly or indirectly cause neurodegeneration. In this study, we report that IL-10, an immunosuppressive cytokine, reduced the inflammation-mediated degeneration of dopaminergic (DA) neurons through the inhibition of microglial activation. Pretreatment of rat mesencephalic neuronglia cultures with IL-10 significantly attenuated the lipopolysaccharide (LPS) induced DA neuronal degeneration. The neuroprotective effect of IL-10 was attributed to inhibition of LPS-stimulated microglial activation. IL-10 significantly inhibited the microglial production of tumor necrosis factor alpha (TNF-alpha), nitric oxide, ROS and superoxide free radicals after LPS stimulation.

Strategies for effective postoperative pain management.

Postoperative pain management an important clinical issue. The clinicians tool-bag remains incomplete. Improvements in the management of postoperative pain will ultimately translate into the broader, safer application of surgical procedures upon a wider patient population. The application of multimodal therapy that includes non-pharmacologic therapies, preemptive therapies, and new medications for the treatment of postoperative pain is an emerging concept that provides significant immediate as well as potential future advantages.

Ovarian and placental production of progesterone and oestradiol during pregnancy in reindeer.

We obtained uterine and peripheral venous plasma, and samples of luteal and placental tissues from 2- to 7-year-old, Eurasian mountain reindeer (Rangifer tarandus tarandus) from a free-living, semi-domesticated herd in northern Norway in November 1995, and February and March 1996. In November, ovarian venous blood was also collected from four animals. Plasma samples were assayed for progesterone and oestradiol. The tissue samples were examined by light and electron microscopy, steroid dehydrogenase histochemistry, and northern blot analysis for RNAs for 3beta-hydroxy-steroid dehydrogenase (3beta-HSD) and P450 (side chain cleavage (scc)). Peripheral blood was taken from non-pregnant females in the same herd on the same dates. Peripheral progesterone concentrations in pregnant reindeer (3.4 +/- 0.5 ng/ml, n = 8) clearly exceeded those in non-pregnant animals (0.40 +/- 0.14 ng/ml; P < 0.0004 , n = 10) but oestradiol levels were only marginally higher in pregnant (6.0 +/- 0.7 pg/ml) than in non-pregnant (4.8 +/- 0.5 pg/ml; P = 0.35) reindeer at the stages examined. In pregnant animals, peripheral progesterone and oestradiol concentrations rose slightly between November and March but the differences did not reach significance (progesterone, P = 0.083; oestradiol, P = 0.061). In November, progesterone concentrations in the ovarian vein (79 +/- 15 ng/ml) greatly exceeded (P < 0.03) those in the uterine vein ( 10 +/- 4 ng/ml) which in turn exceeded the levels in the peripheral blood (2.8 +/- 0.4 ng/ml; P < 0.29). Oestradiol concentrations were slightly but significantly (P < 0.05) higher in the ovarian (20 +/- 3 pg/ml) than the uterine vein (13 +/- 1 pg/ml) and, in turn, greater (P < 0.03) than in peripheral blood (4.6 +/- 0.4 pg/ml). All samples of luteal tissue consisted exclusively of normal fully-differentiated cells and stained intensely for 3beta-HSD. Isolated groups of placental cells also stained strongly for 3beta-HSD. RNA for P450 (scc) and 3beta-HSD was abundant in all corpora lutea and lower concentrations of P450 (scc) were present in the placenta. 3beta-HSD RNA in the placenta was below the limit of detection. We conclude that the corpus luteum remains an important source of progesterone throughout pregnancy in reindeer but that the placenta is also steroidogenic.

Effect of dextrometorphan and dextrorphan on nicotine and neuronal nicotinic receptors: in vitro and in vivo selectivity.

The effects of dextrometorphan and its metabolite dextrorphan on nicotine-induced antinociception in two acute thermal pain assays after systematic administration were evaluated in mice and compared with that of mecamylamine. Dextrometorphan and dextrorphan were found to block nicotine's antinociception in the tail-flick and hot-plate tests with different potencies (dextrometorphan is 10 times more potent than its metabolite). This blockade was not due to antagonism of N-methyl-d-aspartate receptors and/or interaction with opiate receptors, since selective drugs of these receptors failed to block nicotine's analgesic effects. Our results with the tail-flick and hot-plate tests showed an interesting in vivo functional selectivity for dextrometorphan over dextrorphan. In oocytes expressing various neuronal acetylcholine nicotinic receptors (nAChR), dextrometorphan and dextrorphan blocked nicotine activation of expressed alpha(3)beta(4), alpha(4)beta(2), and alpha(7) subtypes with a small degree of selectivity. However, the in vivo antagonistic potency of dextrometorphan and dextrorphan in the pain tests does not correlate well with their in vitro blockade potency at expressed nAChR subtypes. Furthermore, the apparent in vivo selectivity of dextrometorphan over dextrorphan is not related to its in vitro potency and does suggest the involvement of other mechanisms. In that respect, dextrometorphan seems to behave as another mecamylamine, a noncompetitive nicotinic receptor antagonist with a preferential activity to alpha(3)beta(4)(*) neuronal nAChR subtypes.

Comparison of nutritional risk screening tools in patients on admission to hospital.

BACKGROUND AND AIMS: Under nutrition has been frequently reported in patients on admission to hospital. Because this is not always detected promptly, screening for nutritional risk on admission has been widely advocated. Although there is no universally accepted 'gold standard' for defining undernutrition, the definition used by McWhirter, J.P. & Pennington, C.R. [(1994) Br. Med. J.308, 945] has been widely used by clinical nutrition specialists. This study aimed to compare the efficacy of two frequently used nutritional risk screening tools in detecting undernutrition according to this definition. METHODS: Both the Nutrition Risk Index [Veterans Affairs Total Parenteral Nutrition Co-operative Study Group (1991) N. Engl. J. Med.325, 525] and the Nutrition Risk Score [Reilly H.M. et al. (1995) Clin. Nutr.14, 269] were used to screen for undernutrition in 359 admissions to two acute teaching hospitals in Dublin. Undernutrition was defined as a Body Mass Index below 20 kg m(-2) and a triceps skinfold thickness or mid-arm muscle circumference below the 15th percentile. Comparison of stratification of nutritional risk by the two screening tools was carried out. RESULTS: Both screening tools identified over 40% (Nutrition Risk Index, 44%; Nutrition Risk Score, 46%) of all patients assessed as at nutritional risk on admission. However, one-third of the undernourished patients were classified as at no nutrition risk by the Nutrition Risk Index, while almost one-fifth of those undernourished were classified as at low risk by the Nutrition Risk Score. The degree of nutritional risk differed with the screening tool used, the Nutrition Risk Score classifying 29% of all patients as high risk while the Nutrition Risk Index classified only 5% as in the high risk category. CONCLUSIONS: Although a large proportion of patients on admission were classified as being at nutritional risk, the degree of risk was significantly different depending on the screening tool used. Both nutritional risk screening tools evaluated in this study failed to recognize many cases of undernutrition. Evaluation of the efficacy of nutritional screening tools should be promoted as seriously as the development of such tools.

Isolation and properties of the luciferase stored in the ovary of the scyphozoan medusa Periphylla periphylla.

Bioluminescence of the medusa Periphylla is based on the oxidation of coelenterazine catalyzed by luciferase. Periphylla has two types of luciferase: the soluble form luciferase L, which causes the exumbrellar bioluminescence display of the medusa, and the insoluble aggregated form, which is stored as particulate material in the ovary, in an amount over 100 times that of luciferase L. The eggs are especially rich in the insoluble luciferase, which drastically decreases upon fertilization. The insoluble form could be solubilized by 2-mercaptoethanol, yielding a mixture of luciferase oligomers with molecular masses in multiples of approximately 20 kDa. Those having the molecular masses of 20 kDa, 40 kDa, and 80 kDa were isolated and designated, respectively, as luciferase A, luciferase B, and luciferase C. The luminescence activities of Periphylla luciferases A, B, and C were 1.2 approximately 4.1 x 10(16) photon/mg. s, significantly higher than any coelenterazine luciferase known, and the quantum yields of coelenterazine catalyzed by these luciferases (about 0.30 at 24 degrees C) are comparable to that catalyzed by Oplophorus luciferase (0.34 at 22 degrees C), which has been considered the most efficient coelenterazine luciferase until now. Luciferase L (32 kDa) could also be split by 2-mercaptoethanol into luciferase A and an accessory protein (approx. 12 kDa), as yet uncharacterized. Luciferases A, B, and C are highly resistant to inactivation: their luminescence activities are only slightly diminished at pH 1 and pH 11 and are enhanced in the presence of 1 approximately 2 M guanidine hydrochloride; but they are less stable to heating than luciferase L, which is practically unaffected by boiling.

Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant alpha7 and alpha4beta2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes.

1. Ketamine is a dissociative anaesthetic that is formulated as Ketalar, which contains the preservative benzethonium chloride (BCl). We have studied the effects of pure racemic ketamine, the preservative BCl and the Ketalar mixture on human neuronal nicotinic acetylcholine receptors (nAChRs) composed of the alpha7 subunit or alpha4 and beta2 subunits expressed in Xenopus laevis oocytes. 2. Ketamine inhibited responses to 1 mM acetylcholine (ACh) in both the human alpha7 and alpha4beta2 nAChRs, with IC(50) values of 20 and 50 microM respectively. Inhibition of the alpha7 nAChRs occurred within a clinically relevant concentration range, while inhibition of the alpha4beta2 nAChR was observed only at higher concentrations. The Ketalar formulation inhibited nAChR function more effectively than was expected given its ketamine concentration. The surprising increased inhibitory potency of Ketalar compared with pure ketamine appeared to be due to the activity of BCl, which inhibited both alpha7 (IC(50) value of 122 nM) and alpha4beta2 (IC(50) value of 49 nM) nAChRs at concentrations present in the clinical formulation of Ketalar. 3. Ketamine is a noncompetitive inhibitor at both the alpha7 and alpha4beta2 nAChR. In contrast, BCl causes a parallel shift in the ACh dose-response curve at the alpha7 nAChR suggesting competitive inhibition. Ketamine causes both voltage-dependent and use-dependent inhibition, only in the alpha4beta2 nAChR. 4. Since alpha7 nAChRs are likely to be inhibited during clinical use of Ketalar, the actions of ketamine and BCl on this receptor subtype may play a role in the profound analgesia, amnesia, immobility and/or autonomic modulation produced by this anaesthetic.

Home tube feeding: an integrated multidisciplinary approach.

BACKGROUND: Long-term enteral tube feeding is increasingly required by patients in the community setting. A previous study of 50 adults on home enteral tube feeding in the Dublin area found that some experienced logistical problems and many individuals did not choose to seek advice from their GP regarding their tube feeding. AIMS: To assess the contribution of health professionals to the care of patients on enteral tube feeding in the community. METHODS: GPs and hospital dietitians were surveyed using postal questionnaires and nutritional company representatives using structured interviews, to assess their involvement with patients on home tube feeding. Completed questionnaires were received from 77 dietitians and 80 GPs. Ten company representatives were interviewed. RESULTS: Hospital dietitians carry out most of the initial education and training of patients, in addition to the nutritional aftercare. General practitioners tend not to be involved, although nutrition specialists working in the nutritional products area report encountering patients with tube-feeding complications in the community. CONCLUSIONS: Improved co-ordination between hospital and community services and more consistent monitoring of those on home enteral tube feeding would be an advantage to such patients.

General anesthetic potencies of a series of propofol analogs correlate with potency for potentiation of gamma-aminobutyric acid (GABA) current at the GABA(A) receptor but not with lipid solubility.

A series of 27 analogs of the general anesthetic propofol (2,6-diisopropylphenol) were examined for general anesthetic activity in Xenopus laevis tadpoles and for the ability to produce enhancement of submaximal GABA responses and/or direct activation at recombinant GABA(A) receptors. Fourteen of the propofol analogs produced loss of righting reflex in the tadpoles, whereas 13 were inactive as anesthetics. The same pattern of activity was noted with the actions of the compounds at the GABA(A) alpha(1)beta(2)gamma(2s) receptor. The potencies of the analogs as general anesthetics in tadpoles correlated better with potentiation of GABA responses than direct activation at the GABA(A) alpha(1)beta(2)gamma(2s) receptor. The calculated octanol/water partition coefficients for the analogs did not explain the lack of activity exhibited by the 13 nonanesthetic analogs, although this physicochemical parameter did correlate modestly with in vivo anesthetic potency. The actions of one nonanesthetic analog, 2,6-di-tert-butylphenol, were examined in detail. 2,6-Di-tert-butylphenol was inactive at GABA(A) receptors, did not function as an anesthetic in the tadpoles, and did not antagonize any of the actions of propofol at GABA(A) receptors or in tadpoles. A key influence on the potency of propofol analogs appears to be the size and shape of the alkyl groups at positions 2 and 6 of the aromatic ring relative to the substituent at position 1. These data suggest steric constraints for the binding site for propofol on the GABA(A) receptor.