Response of bispectral index to neuromuscular block in awake volunteers.

BACKGROUND: The bispectral index (BIS) monitor is a quantitative electroencephalographic (EEG) device that is widely used to assess the hypnotic component of anaesthesia, especially when neuromuscular blocking drugs are used. It has been shown that the BIS is sensitive to changes in electromyogram (EMG) activity in anaesthetized patients. A single study using an earlier version of the BIS showed that decreased EMG activity caused the BIS to decrease even in awake subjects, to levels that suggested deep sedation and anaesthesia. METHODS: We administered suxamethonium and rocuronium to 10 volunteers who were fully awake, to determine whether the BIS decreased in response to neuromuscular block alone. An isolated forearm technique was used for communication during the experiment. Two versions of the BIS monitor were used, both of which are in current use. Sugammadex was used to antagonise the neuromuscular block attributable to rocuronium. RESULTS: The BIS decreased after the onset of neuromuscular block in both monitors, to values as low as 44 and 47, and did not return to pre-test levels until after the return of movement. The BIS showed a two-stage decrease, with an immediate reduction to values around 80, and then several minutes later, a sharp decrease to lower values. In some subjects, there were periods where the BIS was <60 for several minutes. The response was similar for both suxamethonium and rocuronium. Neither monitor was consistently superior in reporting the true state of awareness. CONCLUSIONS: These results suggest that the BIS monitor requires muscle activity, in addition to an awake EEG, in order to generate values indicating that the subject is awake. Consequently, BIS may be an unreliable indicator of awareness in patients who have received neuromuscular blocking drugs. CLINICAL TRIAL REGISTRY NUMBER: ACTRN12613000587707.

The Role the Frailty Syndrome Can Play in Advocacy and Resource Allocation for Our Ageing Population - Findings in a Dublin Day Hospital.

Frail individuals are at higher risk of adverse outcomes, and need identification and priority access to Comprehensive Geriatric Assessment (CGA). We prospectively collected data on new referrals to our day hospital. Levels of frailty were measured with the SHARE Frailty Instrument for Primary Care (SHARE-FI). Of 257 patients assessed (90 men, 167 women), 110 (43%) were non-frail, 66 (26%) pre-frail and 81 (32%) frail. Mean age was 82 years for the non-frail, 83 for the pre-frail and 84 for the frail. Forty-one percent of the frail reported two or more falls in the preceding year, compared to 38% of the pre-frail and 21% of the non-frail (P for trend = 0.003). Of 27 patients who were referred for ongoing multidisciplinary assessment and rehabilitation, 16 (59%) were frail. The frailty syndrome has the potential to become an advocacy tool for older people and help target effective, but finite, CGA resources.

Rheumatic heart disease in pregnancy: cardiac and obstetric outcomes.

BACKGROUND: Rheumatic heart disease (RHD) remains an important health issue for indigenous women of child-bearing age in northern Australia. However, the influence of RHD on maternal outcomes with current clinical practice is unclear. AIMS: To determine maternal cardiac complications and obstetric outcomes in patients with RHD. METHODS: Retrospective case note analysis of women with RHD who received obstetric care between July 1999 and May 2010 at Cairns Base Hospital in north Queensland. Outcome measures were obstetric interventions and outcomes, cardiac interventions and complications, stratified according to a cardiac risk score (CRS). RESULTS: Ninety-five confinements occurred in 54 patients, of whom 52 were Indigenous Australians. There were no maternal or neonatal deaths. With a CRS of 0, cardiac complications occurred in 0 of 70 confinements; with a CRS of 1, complications occurred in 5 of 17 confinements (29%); with a CRS of >1, complications occurred in 2 of 4 confinements (50%). Another four patients were first diagnosed with RHD after developing acute pulmonary oedema during the peripartum period. CONCLUSIONS: RHD has a major impact on maternal cardiac outcomes. However, with current management practices, maternal and fetal mortality are low, and the incidence of complications is predictable based on known risk factors.

Intravenous oxytocin bolus of 2 units is superior to 5 units during elective Caesarean section.

BACKGROUND: The optimal dose of oxytocin at Caesarean section is unclear. Oxytocin may cause adverse cardiovascular effects, including tachycardia and hypotension, whereas an inadequate dose can result in increased uterine bleeding. We compared the effects of two doses of oxytocin in a randomized double-blind trial. METHODS: Eighty patients undergoing elective Caesarean section received an i.v. bolus of either 2 or 5 units (u) of oxytocin after delivery, followed by an oxytocin infusion of 10 u h(-1). All received combined spinal-epidural anaesthesia with arterial pressure maintained by a phenylephrine infusion. We compared changes in heart rate (HR), mean arterial pressure (MAP), blood loss, uterine tone, the need for additional uterotonic drugs, and emetic symptoms. RESULTS: There was a greater increase in mean (sd) HR in patients who received 5 u of oxytocin [32 (17) beats min(-1)] than in those who received 2 u [24 (13) beats min(-1)] (P=0.015). There was a larger decrease in MAP in patients who received 5 u [13 (15) mm Hg] than in those who received 2 u [6 (10) mm Hg] (P=0.030). The frequency of nausea and antiemetic use was higher after 5 u (32.5%) than 2 u (5%) (P=0.003). There were no differences in blood loss, uterine tone, or requests for additional uterotonic drugs (17.5% in both groups). CONCLUSIONS: In elective Caesarean section, a 2 u bolus of oxytocin results in less haemodynamic change than 5 u, with less nausea and no difference in the need for additional uterotonics.

Group therapy for patients with psychogenic nonepileptic seizures: a pilot study.

Great advances have been made in the diagnosis of people with psychogenic nonepileptic seizures (PNES) since the advent of video/EEG monitoring. However, treatment options for this population have lagged significantly. This pilot study was undertaken to evaluate whether group therapy done with a psychodynamic focus would offer a useful intervention. Twelve patients entered the study and seven completed at least 75% of the 32 weekly sessions. The Beck Depression Inventory and the Global Severity Index of the Symptom Checklist-90 showed improvement as well as an overall decrease in PNES frequency. The data suggest that group therapy focusing on interpersonal issues may benefit patients with PNES.

Cell adhesion and mechanical properties of a flexible scaffold for cardiac tissue engineering.

Cardiac tissue engineering is focused on obtaining functional cardiomyocyte constructs to provide an alternative to cellular cardiomyoplasty. Mechanical stimuli have been shown to stimulate protein expression and the differentiation of mammalian cells from contractile tissues. Our aim was to obtain a flexible scaffold which could be used to apply mechanical forces during tissue regeneration. Poly(1,8-octanediol-co-citric acid) (POC) is an elastomer that can be processed into scaffolds for tissue engineering. We investigated the effect of modifying the porosity on the mechanical properties of the POC scaffolds. In addition, the effects of the storage method and strain rate on material integrity were assessed. The maximum elongation of POC porous films varied from 60% to 160% of their original length. A decrease in the porosity caused a rise in this elastic modulus. The attachment of HL-1 cardiomyocytes to POC was assessed on films coated with fibronectin, collagen and laminin. These extracellular matrix proteins promoted cell adhesion in a protein-type- and concentration-dependent manner. Therefore, POC scaffolds can be optimised to meet the mechanical and biological parameters needed for cardiac culture. This porous material has the potential to be used for cardiac tissue engineering as well as for other soft tissue applications.

The effect of anisotropic architecture on cell and tissue infiltration into tissue engineering scaffolds.

A common phenomenon in tissue engineering is rapid tissue formation on the outer edge of the scaffold which restricts cell penetration and nutrient exchange to the scaffold centre, resulting in a necrotic core. To address this problem, we generated scaffolds with both random and anisotropic open porous architectures to enhance cell and subsequent tissue infiltration throughout the scaffold for applications in bone and cartilage engineering. Hydroxyapatite (HA) and poly(D,L-lactic acid) (P(DL)LA) scaffolds with random open porosity were manufactured, using modified slip-casting and by supercritical fluid processing respectively, and subsequently characterised. An array of porous aligned channels (400 microm) was incorporated into both scaffold types and cell (human osteoblast sarcoma, for HA scaffolds; ovine meniscal fibrochondrocytes, for P(DL)LA scaffolds) and tissue infiltration into these modified scaffolds was assessed in vitro (cell penetration) and in vivo (tissue infiltration; HA scaffolds only). Scaffolds were shown to have an extensive random, open porous structure with an average porosity of 85%. Enhanced cell and tissue penetration was observed both in vitro and in vivo demonstrating that scaffold design alone can influence cell and tissue infiltration into the centre of tissue engineering scaffolds.

Porous methacrylate scaffolds: supercritical fluid fabrication and in vitro chondrocyte responses.

This paper describes a method of foaming a polymer system comprising poly(ethyl methacrylate)/tetrahydrofurfuryl methacrylate (PEMA/THFMA), characterisation of the resulting porosity and use of the foam for chondrocyte culture. The potential for this polymer system to support cartilage repair has been investigated previously, both in vivo and in vitro. PEMA/THFMA foamed created using supercritical carbon dioxide were characterised using scanning electron microscopy, mercury intrusion porosimetry and helium pycnometry. Foams were found to be 82% porous with open porosities of 57%. The mean pore diameter was found to be 99+60 microm. Bovine chondrocytes seeded directly onto the surface of the foamed and unfoamed PEMA/THFMA demonstrated lower proliferation on the foamed material, greater retention of the rounded cell morphology and increased glycosaminoglycan synthesis. In conclusion, this study has shown that a porous PEMA/THFMA system can further enhance the ability of the material to support chondrocytes in vitro. However, further modifications in processing are necessary to determine optimum conditions for cartilage tissue formation.

Fetal heart rate decelerations during ECT-induced seizures: is it important?

Electroconvulsive therapy (ECT) is sometimes indicated during pregnancy and may offer advantages over pharmacotherapy for the patient and the fetus (1,2). However, very little data is available on the impact of epileptic or ECT-induced seizures on the fetus. We report a case of brief fetal heart rate decelerations in a fetus associated with maternal ECT-induced convulsions.

Comparative trial of local pharmacotherapy with L-arginine, r-hirudin, and molsidomine to reduce restenosis after balloon angioplasty of stenotic rabbit iliac arteries.

PURPOSE: To determine if local application of L-arginine, r-hirudin, or molsidomine significantly reduces restenosis after balloon angioplasty in stenotic rabbit iliac arteries. MATERIALS AND METHODS: Thirty-one male cholesterol-fed New Zealand white rabbits underwent balloon dilation of both common iliac arteries to induce arterial stenosis. Four weeks later, one stenotic iliac artery was simultaneously dilated and received local application of L-arginine (210 mg/mL, n = 7), r-hirudin (0.5 mg/mL, n = 8), or molsidomine (0.2 mg/mL, n = 8) with a channeled balloon catheter. On the contralateral side, 0.9% saline was injected as a control. In eight sham animals, saline was applied to one iliac artery and balloon dilation to only the contralateral artery. Six weeks after local treatment, vessels were harvested, and computerized morphometric and immunohistologic analyses were performed. RESULTS: Application of drugs resulted in a significant reduction of neointimal area as follows: 53% with L-arginine (1.01 mm(2) vs. 2.17 mm(2), P <.05), 43% with molsidomine (1.04 mm(2) vs. 1.89 mm(2), P <.05), and 20% with r-hirudin (1.79 mm(2) vs. 2.24 mm(2), P <.05). Infusion of saline led to a significant increase (50%, 1.21 mm(2) vs. 1.93 mm(2), P <.05) in neointimal area compared with balloon dilation alone. Immunohistologic findings showed a significant reduction of macrophages (5.0% vs. 10.2%, P <.05) and proliferating cells (6.2% vs. 10.6%, P <.05) in the neointima after local application of L-arginine. CONCLUSION: Reduction of neointimal area was significant for L-arginine and molsidomine but not for r-hirudin. Saline infusion caused significant arterial trauma, resulting in additional neointimal proliferation.

Transcytosis of gastrointestinal epithelial cells by Escherichia coli K1.

Escherichia coli K1 is an important neonatal pathogen that is usually transferred from maternal to infant gastrointestinal tract at the time of parturition. Approximately 20% of neonates are colonized, and a proportion of colonized infants goes on to have systemic infection. Entry into the bloodstream from the gastrointestinal tract is hypothesized to occur via epithelial cell invasion. Invasion of multiple epithelial cell lines was studied using gentamicin protection assays and transcytosis of polarized monolayers. Electron microscopy was used to confirm cellular invasion. Cell lines used include two human gastrointestinal lines, Caco-2 and T84; a human respiratory cell line, A549; a human laryngeal cell line, HEp-2; and a canine kidney cell line, MDCK. A virulent E. coli K1 strain, RS218, readily invaded HEp-2, A549, and T84 cell lines in gentamicin protection assays, but was less invasive into MDCK and Caco-2 cells. RS218 also demonstrated transcytosis of both T84 and Caco-2 cells. Four clinical isolates of E. coli K1 demonstrated levels of transcytosis of T84 cells similar to RS218. Caco-2 invasiveness correlated with length of time in tissue culture with maximum invasiveness demonstrated at 11 d in culture, when cells were polarized and differentiated.

Etiology, diagnosis, and treatment of nonepileptic seizures.

Psychogenic nonepileptic seizures (NES) can be classified into five categories. This review focuses on NES associated with emotional conflict, by far the most common and important group. Etiology is speculative, but the background histories of these patients are often similar. The presence of a trauma history, depression, post-traumatic stress symptoms, and the use of dissociation plus cognitive dysfunction possibly point to an organic etiology. The presentation of NES in children and adults is discussed, along with the differential diagnosis. The diagnostic differential is lengthy, with epileptic seizures of frontal lobe origin presenting a unique challenge. Diagnostic procedures are reviewed with an emphasis on the utility of hypnosis with seizure induction. Presenting the diagnosis to the patient, the role of the neurologist, and the role of the mental health consultant are reviewed. Issues in the doctor-patient relationship are also addressed, as well as the overall prognosis.

Nonepileptic seizures: an overview.

Since before the time of Charcot, nonepileptic seizures (NES) have intrigued and perplexed physicians. With the advent of the electroencephalogram, particularly with the addition of continuous video monitoring, the diagnosis of NES has received increasing evaluation. Characteristic historical features and clinical signs of NES, coupled with new diagnostic techniques, have progressively refined our understanding of the disorder. The treatment of patients who have NES has received much less attention and the prognosis of these patients illustrates the need for a more comprehensive, systematic, and validated intervention. These issues are discussed with an emphasis on the need for future research.

Local delivery of nadroparin via hydrogel-coated angioplasty balloon: effect on platelet deposition and smooth muscle cell proliferation--an experimental study.

PURPOSE: To assess the feasibility of intravascular delivery of nadroparin, a low-molecular-weight heparin, via hydrogel-coated angioplasty balloons, and the effects of nadroparin delivered in this manner on platelet deposition and smooth muscle cell (SMC) proliferation. MATERIALS AND METHODS: Tritiated nadroparin was used to determine the nadroparin-carrying capacity of the hydrogel-coating, kinetics of release from the balloons, and, in four pigs, delivery of the nadroparin to the iliac arterial wall. Platelet deposition in nadroparin-treated iliac arteries versus contralateral iliac arteries dilated with saline-loaded, hydrogel-coated balloons was quantified in seven pigs using 111Indium-labeled platelets. Smooth muscle cell proliferation in nadroparin and saline-treated iliac arteries in 10 pigs was evaluated 7 days after angioplasty with use of proliferating cell nuclear antigen. RESULTS: Approximately 98 international units of nadroparin were delivered by the hydrogel-coated balloon, the majority to the angioplasty site and distal vessel. There was a trend toward decreased platelet deposition in nadroparin-treated arteries, but statistical significance was not achieved (P = .1563). Medial SMC proliferation was decreased in the nadroparin-treated arteries in nine of 10 pigs (P = .0137). CONCLUSIONS: Hydrogel-coated balloons may be used to deliver nadroparin to the arterial wall, with measurable levels of the drug delivered to the site of angioplasty, and with resultant decrease in SMC proliferation.

Analysis of adenoviral transport mechanisms in the vessel wall and optimization of gene transfer using local delivery catheters.

Local delivery devices have been used for adenovirus-mediated gene transfer to the arterial wall for the potential treatment of vascular proliferative diseases. However, low levels of adenoviral gene expression in vascular smooth muscle cells may pose a serious limitation to the success of these procedures in the clinic. In this study, we examined the mechanisms controlling adenoviral transport to the vessel wall, using both hydrogel-coated and infusion-based local delivery catheters, with the goal of enhancing in vivo gene transfer under clinically relevant delivery conditions. The following delivery parameters were tested in vivo: applied transmural pressure, viral solution volume and concentration, and delivery time. We found that viral particles are transported into the vessel wall in a manner consistent with diffusion rather than pressure-driven convection. Consistent with diffusion, viral concentration was shown to be the key variable for viral transport in the vessel wall and thus gene expression in vascular smooth muscle cells. A transduction level of 17.8+/-3.2% was achieved by delivering a low volume of concentrated adenoviral beta-galactosidase solution through an infusion balloon catheter at low pressure without an adverse effect on medial cellularity. Under these conditions, effective gene transfer was accomplished within a clinically relevant time frame of 2 min, indicating that longer delivery times may not be necessary to achieve efficient gene transfer.

Discriminating between epileptic and nonepileptic events: the utility of hypnotic seizure induction.

PURPOSE: To determine the validity of the Hypnotic Induction Profile (HIP) followed by seizure induction during continuous video-electroencephalographic (EEG) monitoring to discriminate between epileptic (EE) and nonepileptic events (NEE). METHODS: Eighty-two patients admitted to the Stanford Comprehensive Epilepsy Center for differential diagnosis of seizure-like events were evaluated. Exclusion criteria included inability or refusal to complete the HIP, lack of a "typical" event, an IQ <70, present evidence of psychosis, or a physiological cause for NEE. Sixty-nine patients met these criteria. While undergoing continuous video-EEG monitoring, the patient completed an HIP, an inventory designed to measure the degree of hypnotizability. An attempt was then made to induce the patient's typical events under hypnosis by using a split-screen technique. An event without an EEG correlate was thought to represent an NEE. A diagnosis of NEE was made independently by the neurology team and was compared with results obtained with the hypnotic evaluation. RESULTS: Results for patients with EE were compared with those with NEE and a group consisting of both EE/NEE. All patients with NEE were then contrasted with the EE group. HIP scores for the EE patients indicated lower hypnotizability than the NEE group and were statistically significant when NEE patients and those with NEE/EE were combined. The sensitivity of seizure induction in the diagnosis of NEE was 77%, with a specificity of 95%. CONCLUSIONS: The HIP coupled with seizure induction is a useful technique to aid in the diagnosis of patients with NEE. It is sensitive and specific, and it may provide the patient with a useful behavioral tool to control NEEs. It may also furnish a conduit for long-term treatment.

The impact of an acute pain service on postoperative pain management.

An audit of postoperative pain management was conducted before and after the introduction of an Acute Pain Service (APS) run entirely by medical staff. The ability of patients to complete two pain-scoring systems, a verbal rating score (VRS) and a numerical rating score (NRS, where 0 = no pain, 10 = worst pain) was compared. We surveyed 605 adults 24 hours postoperatively. For major operations, the incidence of "severe" or "unbearable" pain at rest (VRS) over the first 24 hours decreased from 18.1% before to 3.5% after the APS (P = 0.0002) and severe/unbearable pain with movement decreased from 50% to 31% (P = 0.0037). The average NRS pain scores fell from 4.65 to 3.37 at rest (P < 0.0001) and from 6.77 to 6.19 with movement (P = 0.046). The incidence of severe/unbearable pain at rest with patient-controlled analgesia (PCA) decreased from 19.7% to 3.2% after the APS (P = 0.0012) and with movement from 51.3% to 35.1% (P = 0.049). For epidural analgesia, severe/unbearable pain at rest was 18.8% prior to the APS and 4.4% after (P = 0.14), and with movement was 43.8% before and 19.1% after (P = 0.079). The NRS pain-scoring system was unsuitable for Aboriginal or Torres Strait Islander patients. Patient satisfaction was high both before and after the introduction of the APS, and was an unreliable indicator of effective pain relief. We conclude that an APS can improve postoperative pain control with PCA and epidural analgesia.