Emotional scene processing in biotypes of psychosis.

Social-emotional deficits in psychosis may be indexed by deviations in emotional scene processing, but event-related potential (ERP) studies indicate such deviations may not map cleanly to diagnostic categories. Neurobiologically defined psychosis subgroups offer an alternative that may better capture neurophysiological correlates of social-emotional deficits. The current study investigates emotional scene-elicited ERPs in Biotypes of psychosis in a large (N = 622), well-characterized sample. Electroencephalography was recorded in healthy persons (N = 129), Biotype-1 (N = 195), Biotype-2 (N = 131), and Biotype-3 (N = 167) psychosis cases. ERPs were measured from posterior and centroparietal scalp locations. Neural responses to emotional scenes were compared between healthy and psychosis groups. Multivariate group discrimination analyses resulted in two composite variates that differentiated groups. The first variate displayed large differences between low-cognition (Biotype-1, Biotype-2) and intact-cognition groups (Biotype-3, healthy persons). The second indicated a small-to-moderate distinction of Biotypes-2 and -3 from Biotype-1 and healthy persons. Two multivariate correlations were identified indicating associations between 1) self-reported emotional experience and generalized cognition and 2) socio-occupational functioning and late-stage emotional processing. Psychosis Biotypes displayed emotional processing deficits not apparent in DSM psychosis subgroups. Future translational research may benefit from exploring emotional scene processing in such neurobiologically-defined psychosis groups.

Oxidative Maturation and Structural Characterization of Prenylated FMN Binding by UbiD, a Decarboxylase Involved in Bacterial Ubiquinone Biosynthesis.

The activity of the reversible decarboxylase enzyme Fdc1 is dependent on prenylated FMN (prFMN), a recently discovered cofactor. The oxidized prFMN supports a 1,3-dipolar cycloaddition mechanism that underpins reversible decarboxylation. Fdc1 is a distinct member of the UbiD family of enzymes, with the canonical UbiD catalyzing the (de)carboxylation of para-hydroxybenzoic acid-type substrates. Here we show that the Escherichia coli UbiD enzyme, which is implicated in ubiquinone biosynthesis, cannot be isolated in an active holoenzyme form despite the fact active holoFdc1 is readily obtained. Formation of holoUbiD requires reconstitution in vitro of the apoUbiD with reduced prFMN. Furthermore, although the Fdc1 apoenzyme can be readily reconstituted and activated, in vitro oxidation to the mature prFMN cofactor stalls at formation of a radical prFMN species in holoUbiD. Further oxidative maturation in vitro occurs only at alkaline pH, suggesting a proton-coupled electron transfer precedes formation of the fully oxidized prFMN. Crystal structures of holoUbiD reveal a relatively open active site potentially occluded from solvent through domain motion. The presence of a prFMN sulfite-adduct in one of the UbiD crystal structures confirms oxidative maturation does occur at ambient pH on a slow time scale. Activity could not be detected for a range of putative para-hydroxybenzoic acid substrates tested. However, the lack of an obvious hydrophobic binding pocket for the octaprenyl tail of the proposed ubiquinone precursor substrate does suggest UbiD might act on a non-prenylated precursor. Our data reveals an unexpected variation occurs in domain mobility, prFMN binding, and maturation by the UbiD enzyme family.

Patient outcomes using Wii-enhanced rehabilitation after total knee replacement - the TKR-POWER study.

BACKGROUND: Home-based rehabilitation following total knee replacement surgery can be as effective as clinic-based or in-patient rehabilitation. The use of the Nintendo Wii has been postulated as a novel rehabilitation tool that adds an additional focus on balance and proprioception into the recovery protocol. The aim of the proposed clinical trial is to investigate the effectiveness of this novel rehabilitation tool, used at home for three months after total knee replacement surgery and to assess any lasting improvements in functional outcome at one year. METHODS/DESIGN: This will be a randomised controlled trial of 128 patients undergoing primary total knee replacement. The participants will be recruited preoperatively from three surgeons at a single centre. There will be no change to the usual care provided until 6 weeks after the operation. Then participants will be randomised to either the Wii-Fit group or usual rehabilitative care group. Outcomes will be assessed preoperatively, a 6-week post surgery baseline and then at 18 weeks, 6 months and 1 year. The primary outcome is the change in self-reported WOMAC total score from week 6 to 18 weeks. Secondary outcomes include objective measures of strength, function and satisfaction scores. DISCUSSION: The results of this clinical trial will be directly relevant for implementation into clinical practice. If beneficial, this affordable technology could be used by many patients to rehabilitate at home. Not only could it optimize the outcomes from their total knee replacement surgery but decrease the need for clinic-based or outpatient therapy for the majority. TRIAL REGISTRATION: (ACTRN12611000291987).

GABA heteroreceptors modulate noradrenaline release in human dental pulp.

γ-aminobutyric-acid-containing neurons and GABA(B) receptors have been identified in human dental pulp; however, their significance in pulpal physiology is unclear. The purpose of this study was to determine whether pre-synaptic GABAergic heteroreceptors influence the release of noradrenaline (NA). Segments of vital pulp were incubated in [(3)H]NA (0.6 µM) and superfused with Krebs solution. GABA, a GABA(B) receptor agonist (baclofen), GABA(A and B) receptor antagonists [bicuculline and (+)-(S)-5, 5-dimethylmorpholinyl-2-acetic acid (Sch 50911), respectively], and a GABA(A) receptor-mediated Cl(-) channel inhibitor (picrotoxin) were added to the superfusion medium at least 10 min prior to the second period of stimulation (S2). Sympathetic nerves were stimulated electrically after 70 (S1) and 115 (S2) min. We determined the effects of agonists/antagonists by comparing the overflow of [(3)H]NA at S2 with that at S1 in the presence and absence of the compound. Baclofen (3 µM) inhibited the release of [(3)H]NA (IC50 = 2 µM), an action reversed by Sch 50911 (10 µM). GABA (100 µM) inhibited the release of [(3)H]NA (IC50 = 75 µM), an effect reversed by Sch 50911 (10 µM) but not by bicuculline (10 µM). However, picrotoxin (100 µM) prevented the inhibitory action of GABA. GABA(B) and GABA(A) heteroceptors mediate the release of NA from sympathetic nerves in human dental pulp in vitro.

Can tibial coverage in total knee replacement be reliably evaluated with three-dimensional image-based digital templating?

OBJECTIVES: There remains a lack of data on the reliability of methods to estimate tibial coverage achieved during total knee replacement. In order to address this gap, the intra- and interobserver reliability of a three-dimensional (3D) digital templating method was assessed with one symmetric and one asymmetric prosthesis design. METHODS: A total of 120 template procedures were performed according to specific rotational and over-hang criteria by three observers at time zero and again two weeks later. Total and sub-region coverage were calculated and the reliability of the templating and measurement method was evaluated. RESULTS: Excellent intra- and interobserver reliability was observed for total coverage, when minimal component overhang (intraclass correlation coefficient (ICC) = 0.87) or no component overhang (ICC = 0.92) was permitted, regardless of rotational restrictions. CONCLUSIONS: Measurement of tibial coverage can be reliable using the templating method described even if the rotational axis selected still has a minor influence.

Different changes in slope between the medial and lateral tibial plateau after open-wedge high tibial osteotomy.

PURPOSE: In contrast to radiographic measurements, MRI provides multiple slices of the knee joint in the sagittal plane, making it possible to assess the medial and lateral tibial slope separately. The purpose of this study is to investigate the effect of medial open-wedge high tibial osteotomy (MOWHTO) on bony and meniscal slope in the medial and lateral tibiofemoral compartments. It was hypothesised that greater changes on the medial tibial plateau would be observed compared with the lateral one. METHODS: A retrospective analysis of prospectively collected data was performed on pre- and post-operative MRIs from 21 patients (17 men and 4 women; age 52 ± 9 years). Inclusion criteria were varus alignment, medial compartment osteoarthritis and election for a primary MOWHTO. Each patient had a preoperative and a post-operative high-resolution MRI (3Tesla, Magnetom Trio, Siemens AG) at an average follow-up of 2.1 years. A previously published method was used to measure bony and meniscal slope for each compartment. The difference between pre- and post-operative tibial slope for both compartments was calculated and associated with the amount of frontal correction. RESULTS: There was a significant increase in bony tibial slope in both compartments following MOWHTO. When a change in bony tibial slope was detected in an individual patient, the change was larger in the medial compartment, with the average change also significantly greater (p < 0.01) in the medial compartment (2.4° ± 1.3°) compared with the lateral compartment (0.9° ± 1.1°). There was also a significant increase (p < 0.01) in the lateral tibial meniscal slope of 0.9° ± 1.4°, which was equivalent to the change in the bony lateral slope. The amount of frontal correction was not significantly associated with the amount of change in slope. CONCLUSIONS: The results suggest that the modification of the bony slope is larger in the medial compartment after MOWHTO, which is likely related to the location of the hinge on the lateral tibial cortex. These findings suggest that consideration of the medial and lateral tibial slope intra-operatively could be important to identify the optimal location of the hinge. However, further studies are required before recommending any modification to the surgical technique, as the potential clinical consequences of tibial slope alterations remain unknown. LEVEL OF EVIDENCE: IV.

Patient preparation for intravenous urography: are we practising evidence-based medicine?

AIM: To identify the current practice of patient preparation prior to intravenous urography (IVU) in England and Wales. METHODS: Seventy-two hospitals were contacted to request details regarding the duration of fluid restriction, adherence to a low-residue diet, or use of laxatives for patient preparation before IVU examinations. RESULTS: Results showed that out of 45 hospitals that still use IVU, only six (13.3%) did not follow a patient-preparation regime. The vast majority of the hospitals contacted (87.6%), implemented either fluid and/or food restriction, or prescribed laxatives. The duration of fluid and food restriction varied from 2-12 h duration, and some departments advocated 48 h of laxatives. CONCLUSION: A large proportion of hospitals are not practising evidence-based medicine in relation to IVU, and we suggest that the practice of patient preparation should be abandoned.

Isolated rupture of the lateral collateral ligament during yoga practice: a case report.

We report a case of isolated rupture of the lateral collateral ligament (LCL) of the knee while attempting to place the left foot behind the head during yoga practice. The 34-year-old man had discomfort of the lateral aspect of the knee particularly with varus strain. A magnetic resonance image revealed rupture of the LCL at the insertion onto the fibula. The patient had grade-II laxity of the LCL and was treated non-operatively. At the 12-month follow-up, grade-I laxity of the LCL remained clinically evident, but function was not impaired.

Complex regional pain syndrome complicating total knee arthroplasty.

PURPOSE: To compare the long-term outcome of patients diagnosed with complex regional pain syndrome-type 1 (CRPS-1) after total knee arthroplasty (TKA) with those of uncomplicated TKA knees and preoperative osteoarthritic knees. METHODS: Medical records of 1280 patients who underwent TKA for osteoarthritis were retrospectively reviewed; 8 were diagnosed as having symptoms and signs consistent with CRPS after TKA. Patients with primary inflammatory arthritis, signs of component loosening, malpositioning, or of infected arthroplasty were excluded. No patient had signs of CRPS prior to operative intervention. The 8 patients were compared with 2 groups of age- and sex-matched controls: uncomplicated TKA knees and preoperative osteoarthritic knees. Patients were followed up for a mean of 54 (range, 13-111) months and their range of movement, Western Ontario and McMaster Universities Osteoarthritis Index, SF-36 questionnaire scores, and Knee Society scores were assessed and compared. RESULTS: After appropriate treatment, most CRPS complicated patients had similar scores on SF-36, Western Ontario and McMaster Universities Osteoarthritis Index, and Knee Society scores when compared with uncomplicated TKA patients. Scores for CRPS complicated patients were significantly improved when compared with preoperative osteoarthritic patients. The incidence of CRPS after TKA was 0.7%. CONCLUSION: When managed early, patients complicated with CRPS after TKA have a similar prognosis to patients with uncomplicated TKA.

Short-term black tea intake modulates the excretion of urinary mutagens in rats treated with 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ): role of CYP1A2 upregulation.

Rats were exposed to black tea (2.5% w/v) as their sole drinking liquid for either 1 day or 1 month, while controls were maintained on water. After this treatment period, all animals received a single oral dose IQ (2-amino-3-methylimidazo-[4,5-f]quinoline), and urine was collected for 48 h. Mutagenic activity of the urine was determined in the Ames test in the presence and absence of an activation system. The excretion of direct-acting mutagens was markedly reduced following tea intake, and was more pronounced after the 1-day treatment. Similarly, both tea treatments suppressed the excretion of indirect-acting mutagens. Furthermore, both tea treatments induced hepatic CYP1A2 activity and expression, but cytosolic glutathione S-transferase activity was only modestly induced in the group of animals receiving tea for 1 day, and only when DCNB (1,2-dichloro-4-nitrobenzene) was used as substrate; glucuronosyl activity was elevated modestly only in the animals receiving the tea for a month. It is concluded that even short-term exposure to black tea is capable of influencing the metabolic fate of IQ, and this is most likely related to the upregulation of CYP1A2.

Uptake and release of [3H]adenosine in human dental pulp.

The purpose of this study was to examine the uptake and release of adenosine in human dental pulp. Pulp was removed from extracted teeth and incubated in [3H]adenosine (0.02-3.2 micromol/l) for 30-90 min, washed for 30 min and the residual [3H]adenosine extracted and assayed. At 0.02 and 0.4 micromol/l the uptake was saturated after 30 min, whereas at 3.2 micromol/l it was not, even after 90 min. Destruction of the sympathetic nerves by 6-hydroxydopamine prior to incubation in [3H]adenosine (0.4 micromol/l) decreased the uptake of [3H] by 40%. Addition of S(4-nitrobenzyl)-6-thioguanosine (NBTG; 0.1 micromol/l), an inhibitor of adenosine uptake, blocked 90% of the uptake. Electrical stimulation of sympathetic nerves following incubation of pulp in [3H]adenosine (0.4 micromol/l) increased the overflow of [3H] into the medium superfusing the tissue segments. NBTG (0.1 micromol/l) had no effect on this overflow, whereas denervation with 6-hydroxydopamine prior to incubation decreased the overflow by 85%. Although the contribution of post-junctional elements, such as smooth muscle, to this release was not determined it is proposed that most of the purine released was derived from sympathetic nerves.

Long-term followup of cementless versus hybrid fixation for total knee arthroplasty.

In a prospective trial, 99 patients (100 knees) with osteoarthritis were randomized to either cementless or hybrid fixation of cruciate-retaining Miller-Galante-I total knee arthroplasties between January 1987 and December 1988. Thirty-one patients died during the study period and two additional patients were lost to followup, leaving 67 total knee arthroplasties for analysis. Thirty-nine patients underwent revision surgery at an average of 6.9 years postoperatively. The main reason for revision surgery was failure of metal-backed patellas with 25 knees revised at an average of 7.4 years, and the second most common reason was tibial polyethylene failure. Survival curves showed 60% survival at 14 years for all knees, and 85% survival at 14 years when failures for metal-backed patellas and infection were excluded, with no significant difference between the two groups. Failure of metal-backed patellas was significantly higher in the cementless group. Tibial polyethylene failure occurred in five of the hybrid group and none of the cementless group, but this was not a significant difference. Surviving prostheses were assessed at an average of 12.8 years (range, 11.5-13.5 years). Average clinical scores were 94.8 points preoperatively, and 143 points at the latest followup, with significantly higher scores in the hybrid group. Differences in outcome between the two groups were not sufficiently significant to recommend one method of fixation over another. With elimination of poor design features related to the patellofemoral articulation and thin tibial polyethylene, cruciate-retaining total knee arthroplasties can yield good durable results, whether cementless or hybrid fixation is used.

CGP 36216 is a selective antagonist at GABA(B) presynaptic receptors in rat brain.

In rat neocortical preparations maintained in Mg(2+)-free Krebs medium, baclofen depressed the frequency of spontaneous discharges in a concentration-dependent manner (EC(50) = 6 microM), sensitive to (3-aminopropyl)ethylphosphinic acid (CGP 36216) (100, 300 and 500 microM) (pA(2) = 3.9 +/- 0.1). By contrast, CGP 36216, up to 1 mM, was ineffective in antagonising baclofen-induced hyperpolarisations, mediated through gamma-aminobutyric acid(B) (GABA(B)) postsynaptic receptors. In electrically stimulated brain slices preloaded with [3H]GABA, CGP 36216 increased [3H]GABA release (IC(50) = 43 microM), which was reversed by baclofen (20 microM). While CGP 36216 is ineffective at GABA(B) postsynaptic receptors, it is appreciably more active at presynaptic receptors.

Comparative activities of the enantiomeric GABA(B) receptor agonists CGP 44532 and 44533 in central and peripheral tissues.

In neocortical slices maintained in Mg(2+)-free Krebs medium, the gamma-aminobutyric acid (GABA(B)) receptor agonists baclofen, (3-amino-2(S)-hydroxypropyl)methylphosphinic acid (CGP 44532), and its (R)-enantiomer CGP 44533 depressed the frequency of spontaneous discharges in a concentration-dependent manner (EC(50)=10, 6.5, and 50 microM, respectively). These effects were reversibly antagonised by the GABA(B) receptor antagonist (+)-(S)-5,5 dimethylmorpholinyl-2-acetic acid (Sch 50911) (3, 10, and 30 microM) (average pA(2) value=6.0+/-0.2). In neocortical wedges, baclofen, CGP 44532 and CGP 44533 elicited concentration-dependent hyperpolarisations (the EC(50)s were 14, 7.5 and 16 microM, respectively) sensitive to Sch 50911 (1, 5, 10 microM) (average pA(2) value=6.0+/-0.1), whilst they also depressed ileal electrically elicited cholinergic twitch contractions (EC(50)=11, 7, and 50 microM) that were antagonised by Sch 50911 (average pA(2) value=6.0+/-0.1). In electrically stimulated brain slices preloaded with [3H]GABA, baclofen, CGP 44532 and CGP 44533 decreased [3H]GABA release (IC(50)=5, 0.45, and 10 microM); this effect was reversed by Sch 50911 (50 microM). It is concluded that CGP 44532 is a far more potent agonist at GABA(B) autoreceptors than at central or peripheral heteroreceptors.

The John Charnley Award: Three-dimensional analysis of the cement mantle in total hip arthroplasty.

Cemented fixation of the femoral stem is the gold standard for patients older than 60 years. The importance of reliably achieving an adequate cement mantle has been shown in many studies. Currently, inspection and grading of plain radiographs is the accepted method for study of the cement mantle. However, the reliability of plain radiographs for this purpose has been questioned. In addition, the interobserver agreement of current grading systems has been shown to be limited. A new in vitro method of cement mantle analysis is described. Plastic replicas of six contemporary stems were implanted into femurs from cadavers. The specimens were imaged with a computed tomography scanner. Detailed, computer-assisted analysis of mantle thickness was done. Comparisons were made between designs. A subset was compared with standard radiographs. Plain radiographs overestimated thickness and underestimated the deficiencies. There was significant variability in the mantle produced by the different designs. Commonly used designs had deficiencies in their mantles by standard criteria despite proper surgical technique. The importance of being fully acquainted with the particular implant one uses is emphasized by these results. This is a valuable technique for investigation of the effects on the cement mantle of implant design, surgical technique, and patient anatomy.

Failure of presynaptic purinoceptors to modulate noradrenaline release from sympathetic nerves in human dental pulp.

The effects of putative presynaptic P1- and/or P2-purinoceptors on the release of noradrenaline from sympathetic nerves in human dental pulp were examined by testing the effects of agonists and an antagonist of these receptors on the stimulation-induced overflow of [(3)H]noradrenaline from tissue treated with desipramine (0.3 micromol/l) and preincubated with [(3)H]noradrenaline (0.6 micromol/l). The P1-purinoceptor agonists adenosine (1.0 mmol/l) and 2-chloroadenosine (0.01-1.0 mmol/l) and the antagonist 8-cyclopentyl-1,3-dipropyl xanthine (1.0 micromol/l), and the P2-purinoceptor agonists ATP (0.1 mmol/l) and beta, gamma-methylene-ATP (0.01 mmol/l), did not modulate the release of noradrenaline. Adenosine was also without effect in dental pulp treated with the alpha(2)-adrenoceptor antagonist rauwolscine. It is concluded that presynaptic P1-purinoceptors and those P2-purinoceptors activated by adenine nucleotides are either not present on sympathetic nerves in human dental pulp or that they exert little or no effect on the release of noradrenaline.

Effect of different types of Medicaid managed care on childhood immunization rates.

Medicaid managed care can improve access to prevention services, such as immunization, for low-income children. The authors studied immunization rates for 7,356 children on Medicaid in three managed care programs: primary care case management (PCCM; n = 4,605), a voluntary HMO program (n = 851), and a mandatory HMO program (n = 1,900). Immunization rates (3:3:1 series) in PCCM (78%) exceeded rates in the voluntary HMO program (71%), which in turn exceeded those in the mandatory HMO program (67%). Adjusting for race, urban residence, and gender, compared to children in PCCM, children in the voluntary HMO program were less likely to complete the 3:3:1 series (OR = 0.75, CI = 0.63, 0.90), and children in the mandatory HMO program were even less likely to complete the series (OR = 0.59, CI = 0.51, 0.68). Results differed by individual HMOs. Monitoring of outcomes for all types of managed care by Medicaid agencies is imperative to assure better disease prevention for low-income children.