A case of metastatic primary cardiac angiosarcoma.

We report a 49-year-old Southeast Asian woman diagnosed with metastatic primary right atrial angiosarcoma (PCA) and the difficulties encountered in this diagnosis and its subsequent management. Diagnosis of PCA is often delayed due to non-specific clinical presentation of patients. These tumours often present once metastatic spread has occurred, restricting treatment options and leading to very poor prognosis. Patients undergo a multidisciplinary team (MDT) approach involving chemotherapy, radiotherapy and, if eligible, surgery, but evidence-based treatment guidelines have yet to be established due to the rarity of the tumour.

Creating a model to predict time intervals from induction of labor to induction of anesthesia and delivery to coordinate workload.

BACKGROUND: Induction of labor continues to become more common. We analyzed induction of labor and timing of obstetric and anesthesia work to create a model to predict the induction-anesthesia interval and the induction-delivery interval in order to co-ordinate workload to occur when staff are most available. METHODS: Patients who underwent induction of labor at a single medical center were identified and multivariable linear regression was used to model anesthesia and delivery times. Data were collected on date of birth, race/ethnicity, body mass index, gestational age, gravidity, parity, indication for labor induction, number of prior deliveries, time of induction, induction agent, cervical dilation, effacement, and fetal station on admission, date and time of anesthesia administration, date and time of delivery, and delivery type. RESULTS: A total of 1746 women met inclusion criteria. Associations which significantly influenced time from induction of labor to anesthesia and delivery included maternal age (anesthesia P <0.001, delivery P =0.002), body mass index (both P <0.001), prior vaginal delivery (both P <0.001), gestational age (anesthesia P <0.001, delivery P <0.018), simplified Bishop score (both P <0.001), and first induction agent (both P <0.001). Induction of labor of nulliparous women at 02:00 h and parous women at 04:00 or 05:00 h had the highest estimated probability of the mother having her first anesthesia encounter and delivering during optimally staffed hours when our institution's specialty personnel are most available. CONCLUSIONS: Time to obstetric and anesthesia tasks can be estimated to optimize induction of labor start times, and shift anesthesia and delivery workload to hours when staff are most available.

Efficient production of a high-performance dispersion strengthened, multi-principal element alloy.

Additive manufacturing currently facilitates new avenues for materials discovery that have not been fully explored. In this study we reveal how additive manufacturing can be leveraged to produce dispersion strengthened (DS), multi-principal element alloys (MPEA) without the use of traditional mechanical alloying or chemical reactions. This new processing technique employed resonant acoustic mixing to coat an equiatomic NiCoCr powder with nano-scale yttrium oxides. Then, through laser powder bed fusion (L-PBF), the coated powder was successfully consolidated into 99.9% dense parts. Microstructural analysis confirmed the successful incorporation and dispersion of nano-scale oxides throughout the build volume. Furthermore, high temperature mechanical testing of the DS alloys showed significant improvements in strength and ductility over the baseline NiCoCr. As a result, this recently discovered processing route opens a new alloy design and production path that is synergistic between additive manufacturing and dispersion strengthening, possibly enabling a new generation of high-performance alloys.

Reliable exclusion of prognostically significant coronary disease in left ventricular dysfunction by cardiac MRI.

AIM: To assess the ability of cardiac magnetic resonance (CMR) to exclude prognostically significant coronary artery disease (CAD) in patients with left ventricular systolic dysfunction (LVSD). MATERIALS AND METHODS: A cohort of patients who underwent both X-ray angiography and CMR since 2006 was reviewed retrospectively. Records of those with European criteria for LVSD (left ventricular ejection fraction [LVEF] <50% or LV end-diastolic volume index [LVEDVI] ≥97 ml/m2) on CMR or transthoracic echo were analysed. The presence and extent of subendocardial late gadolinium enhancement (LGE) was recorded with the 17-segment model. The degree of coronary stenosis at X-ray angiography was assessed visually and significant disease defined as stenosis of the LMS ≥50%, or proximal left anterior descending ≥75%, or ≥70% in two main coronary vessels. RESULTS: One hundred and sixteen patients were included. The mean age was 64 years and 78% were male. The mean LVEF was 40%. The prevalence of prognostic CAD was 47%. The presence of subendocardial LGE detected prognostically significant CAD with a sensitivity of 100% (95% CI: 94-100%) with no false-negative results. CONCLUSIONS: The absence of subendocardial LGE on CMR reliably excludes prognostic CAD in patients with LVSD.

Diet-induced obesity: dopamine transporter function, impulsivity and motivation.

OBJECTIVE: A rat model of diet-induced obesity (DIO) was used to determine dopamine transporter (DAT) function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. DESIGN: To evaluate neurobehavioral alterations following the development of DIO induced by an 8-week high-fat diet (HF) exposure, striatal D2-receptor density, DAT function and expression, extracellular dopamine concentrations, impulsivity, and motivation for high- and low-fat reinforcers were determined. To determine predictors of DIO, neurobehavioral antecedents including impulsivity, motivation for high-fat reinforcers, DAT function and extracellular dopamine were evaluated before the 8-week HF exposure. METHODS: Striatal D2-receptor density was determined by in vitro kinetic analysis of [(3)H]raclopride binding. DAT function was determined using in vitro kinetic analysis of [(3)H]dopamine uptake, methamphetamine-evoked [(3)H]dopamine overflow and no-net flux in vivo microdialysis. DAT cell-surface expression was determined using biotinylation and western blotting. Impulsivity and food-motivated behavior were determined using a delay discounting task and progressive ratio schedule, respectively. RESULTS: Relative to obesity-resistant (OR) rats, obesity-prone (OP) rats exhibited 18% greater body weight following an 8-week HF-diet exposure, 42% lower striatal D2-receptor density, 30% lower total DAT expression, 40% lower in vitro and in vivo DAT function, 45% greater extracellular dopamine and twofold greater methamphetamine-evoked [(3)H]dopamine overflow. OP rats exhibited higher motivation for food, and surprisingly, were less impulsive relative to OR rats. Impulsivity, in vivo DAT function and extracellular dopamine concentration did not predict DIO. Importantly, motivation for high-fat reinforcers predicted the development of DIO. CONCLUSION: Human studies are limited by their ability to determine if impulsivity, motivation and DAT function are causes or consequences of DIO. The current animal model shows that motivation for high-fat food, but not impulsive behavior, predicts the development of obesity, whereas decreases in striatal DAT function are exhibited only after the development of obesity.

Necrotising otitis externa: an unusual cause of cranial nerve palsy in a diabetic haemodialysis patient.

We present an unusual case of necrotising otitis externa (NOE) causing a lower motor neurone facial nerve palsy in a patient with diabetes mellitus and receiving maintenance haemodialysis for end-stage renal disease (ESRD). Pseudomonas aeruginosa is the most common pathogen isolated in NOE, although our case involved the non-typical pathogens Aspergillus flavus and Proteus mirabilis. We discuss the need for diagnostic rigour and the importance of considering atypical infective pathology in patients with ESRD or diabetes mellitus. We review NOE with reference to causative agents, imaging strategies, prognostic indicators and treatment.

Dynamic contrast-enhanced MRI for prostate cancer localization.

Radiotherapy dose escalation improves tumour control in prostate cancer but with increased toxicity. Boosting focal tumour only may allow dose escalation with acceptable toxicity. Intensity-modulated radiotherapy can deliver this, but visualization of the tumour remains limiting. CT or conventional MRI techniques are poor at localizing tumour, but dynamic contrast-enhanced MRI (DCE-MRI) may be superior. 18 patients with prostate cancer had T(2) weighted (T2W) and DCE-MRI prior to prostatectomy. The prostate was sectioned meticulously so as to achieve accurate correlation between imaging and pathology. The accuracy of DCE-MRI for cancer detection was calculated by a pixel-by-pixel correlation of quantitative DCE-MRI parameter maps and pathology. In addition, a radiologist interpreted the DCE-MRI and T2W images. The location of tumour on imaging was compared with histology, and the accuracy of DCE-MRI and T2W images was then compared. Pixel-by-pixel comparison of quantitative parameter maps showed a significant difference between the benign peripheral zone and tumour for the parameters K(trans), v(e) and k(ep). Calculation of areas under the receiver operating characteristic curve showed that the pharmacokinetic parameters were only "fair" discriminators between cancer and benign gland. Interpretation of DCE-MRI and T2W images by a radiologist showed DCE-MRI to be more sensitive than T2W images for tumour localization (50% vs 21%; p = 0.006) and similarly specific (85% vs 81%; p = 0.593). The superior sensitivity of DCE-MRI compared with T2W images, together with its high specificity, is arguably sufficient for its use in guiding radiotherapy boosts in prostate cancer.

Prospective multidisciplinary audit of obstetric general anaesthesia in a district general hospital.

In the 3 years leading up to March 2001, the general anaesthesia rate for emergency and elective caesarean sections at our hospital was higher than that recommended by the Royal College of Anaesthetists. There were also concerns regarding the quality of communication between surgeon and anaesthetist prior to emergency caesarean section. A multidisciplinary audit was undertaken on both the indications for obstetric general anaesthesia and quality of communication between staff members during the perioperative period between January and August 2002. The results of the audit highlighted potential serious shortfalls in communication and teamworking; however, there was insufficient information to assess the appropriateness of the indication for general anaesthesia. Following this audit recommendations were made to improve communication channels between the personnel on labour ward and this coincided with a reduction in the use of general anaesthesia.

Sexual protective strategies of late adolescent females: more than just condoms.

OBJECTIVE: To identify the sexual protective strategies of late adolescent heterosexual women. DESIGN: Open-ended questioning regarding sexual protective strategies was included in a larger cross-sectional survey on sexual risk. Participants' responses were recorded verbatim and analyzed using content analysis. PARTICIPANTS: 234 African American, Hispanic/ Latina, and non-Hispanic white 19- to 21-year-old females were recruited from the driver's license records of a mid-Atlantic state. MAIN OUTCOME MEASURES: Participants responded to the open-ended question, "How or what do you do to reduce your risk for sexually transmitted diseases and HIV?" RESULTS: Seven primary sexual protective strategies were identified from participants' responses: using condoms, abstaining or postponing sexual intercourse, getting tested for human immunodeficiency virus (HIV) and sexually transmitted diseases (STDs), selecting safe partners, negotiating condom use, talking about sexual risk histories, and limiting the number of sexual partners. CONCLUSIONS: Some of the sexual protective strategies identified by study participants were less than effective and left young women vulnerable to infection with HIV and STDs. In addition, the use of these alternative strategies may leave young women feeling less at risk and thus less likely to use other more effective strategies such as condoms. The implications for nursing practice and the assessment of the sexual protective strategies of young heterosexual women are discussed.

Increased patient satisfaction from transrectal ultrasonography and biopsy under sedation.

OBJECTIVE: To determine the acceptability and patient satisfaction of transrectal biopsy undertaken with the patient under sedation. Patients and methods A retrospective questionnaire was sent to 100 patients who had undergone transrectal biopsy between January and August 1998. Levels of patient acceptability and satisfaction were assessed using visual analogue scales (VAS, with a maximum score of 10 being the least satisfactory or acceptable) and direct questions about the side-effects of the procedure. A subsequent prospective study was undertaken on 130 patients undergoing transrectal biopsy with sedation between January 1999 and January 2000. RESULTS: The mean score for patient discomfort with sedation was 1.5, compared with 3.5 with no sedation. The overall satisfaction score improved from 3.1 to 0.9 with sedation. Complication rates were comparable, although slightly higher overall in the prospective group. Conclusion Sedation can significantly reduce patient discomfort and make the transrectal biopsy a more satisfactory experience for the patient. This is particularly important in the proportion of men who need to be considered for repeat biopsies.

Modulation of pre- and postsynaptic dopamine D2 receptor function by the selective kappa-opioid receptor agonist U69593.

The repeated administration of selective kappa-opioid receptor agonists prevents the locomotor activation produced by acute cocaine administration and the development of cocaine-induced behavioral sensitization. Previous studies have shown that dopamine (DA) D2 autoreceptors modulate the synthesis and release of DA in the striatum. Evidence that kappa agonist treatment downregulates DA D2 receptors in this same brain region has recently been obtained. Accordingly, the present studies were undertaken to examine the influence of repeated kappa-opioid receptor agonist administration on pre- and postsynaptic DA D2 receptor function in the dorsal striatum using pre- and postsynaptic receptor-selective doses of quinpirole. Rats were injected once daily with the selective kappa-opioid receptor agonist U69593 (0.16-0.32 mg/kg s.c.) or vehicle for 3 days. Microdialysis studies assessing basal and quinpirole-evoked (0.05 mg/kg s.c.) DA levels were conducted 2 days later. Basal and quinpirole-stimulated locomotor activity were assessed in a parallel group of animals. The no-net flux method of quantitative microdialysis revealed no effect of U69593 on basal DA dynamics, in that extracellular DA concentration and extraction fraction did not differ in control and U69593-treated animals. Acute administration of quinpirole significantly decreased striatal DA levels in control animals, but in animals treated with U69593, the inhibitory effects of quinpirole were significantly reduced. Quinpirole produced a dose-related increase in locomotor activity in control animals, and this effect was significantly attenuated in U69593-treated animals. These data reveal that prior repeated administration of a selective kappa-opioid receptor agonist attenuates quinpirole-induced alterations in DA neurotransmission and locomotor activity. These results suggest that both pre- and postsynaptic striatal DA D2 receptors may be downregulated following repeated kappa-opioid receptor agonist administration. Synapse 39:343-350, 2001. Published 2001 Wiley-Liss, Inc.

Analgesic efficacy of orally administered buprenorphine in rats.

The analgesic effect of orally administered buprenorphine was compared with that induced by a standard therapeutic injected dose (0.05 mg/kg of body weight, s.c.) in male Long-Evans rats. Analgesia was assessed by measuring pain threshold, using the hot-water tail-flick assay before and after administration of buprenorphine. The results suggest that a commonly used formula for oral buprenorphine in flavored gelatin, at a dose of 0.5 mg/kg, does not increase pain threshold in rats. Instead, oral buprenorphine doses of 5 and 10 mg/kg were necessary to induce significant increases in pain threshold. However, these doses had to be administered by orogastric infusion because the rats would not voluntarily eat flavored gelatin containing this much buprenorphine. The depth of analgesia induced by these infused doses was comparable to that induced by the clinically effective s.c. treatment (0.05 mg/kg).

Overview of microdialysis.

The technique of microdialysis enables the monitoring of neurotransmitters and other molecules in the extracellular environment. This method has undergone several modifications and is now widely used for sampling and quantitating neurotransmitters, neuropeptides, and hormones in the brain and periphery. This unit describes the principles of conventional and quantitative microdialysis as well as strategies in designing a dialysis experiment. It establishes the groundwork for the basic techniques of preparation, conduct, and analysis of dialysis experiments in rodents and subhuman primates. Although the methods described are those used for monitoring CNS function, they can be easily applied with minor modification to other organ systems.

Microdialysis in rodents.

Microdialysis is an established sampling technique for the in vivo measurement of a variety of substances in both blood and tissue. These include neurotransmitters and neuropeptides, enzymes, and electrolytes, as well as various hormones and pharmaceutical agents. More recently, microdialysis has been used to infuse exogenous as well as endogenous substances into the brain and spinal cord. In microdialysis, a semipermeable dialysis membrane is introduced into the fluid or tissue compartment to be sampled and perfused with physiological fluid. As a result of passive diffusion, molecules migrate across the membrane along their concentration gradient. Molecules found in high concentrations within the tissue compartment migrate across the membrane into the dialysis tubing where they can be collected for subsequent quantification, whereas molecules found in high concentrations within the membrane diffuse outward into the surrounding tissue compartment. This unit describes construction of concentric and side-by-side microdialysis probes, which differ with respect to size and inflow/outflow tube compositions, as well as a modification of a horizontal probe. This unit also covers methods for surgically implanting microdialysis probes in rats and mice and for conducting microdialysis in vitro and in vivo in rodents. Finally, procedures are provided for carrying out quantitative microdialysis techniques.

Kappa-opioid receptor activation modifies dopamine uptake in the nucleus accumbens and opposes the effects of cocaine.

Coadministration of kappa-opioid receptor agonists (kappa-agonists) with cocaine prevents alterations in dialysate dopamine (DA) concentration in the nucleus accumbens (Acb) that occur during abstinence from repeated cocaine treatment. Quantitative microdialysis was used to determine the mechanism producing these effects. Rats were injected with cocaine (20 mg/kg, i.p.), or saline, and the selective kappa-agonist U-69593 (0.32 mg/kg, s.c.), or vehicle, once daily for 5 d. Extracellular DA concentration (DA(ext)) and extraction fraction (E(d)), an indirect measure of DA uptake, were determined 3 d later. Repeated cocaine treatment increased E(d), whereas repeated U-69593 treatment decreased E(d), relative to controls. Coadministration of both drugs yielded intermediate E(d) values not different from controls. In vitro DA uptake assays confirmed that repeated U-69593 treatment produces a dose-related, region-specific decrease in DA uptake and showed that acute U-69593 administration increases DA uptake in a nor-binaltorphimine reversible manner. Repeated U-69593 also led to a decrease in [(125)I]RTI-55 binding to the DA transporter (DAT), but did not decrease total DAT protein. These results demonstrate that kappa-opioid receptor activation modulates DA uptake in the Acb in a manner opposite to that of cocaine: repeated U-69593 administration decreases the basal rate of DA uptake, and acute U-69593 administration transiently increases DA uptake. kappa-agonist treatment also alters DAT function. The action of kappa-agonists on DA uptake or DAT binding, or both, may be the mechanism(s) mediating the previously reported "cocaine-antagonist" effect of kappa-opioid receptor agonists.

Fixed-exit monochromator for computed tomography with synchrotron radiation at energies 18-90 keV.

A fixed-exit monochromator has been constructed for computed tomography (CT) studies at the Medical Beamline of the European Synchrotron Radiation Facility. A non-dispersive pair of bent Laue-type crystals is used, and the first crystal is water-cooled. The monochromator operates at energies from 18 to 90 keV, and the maximum width of the beam is 150 mm. The performance of the monochromator is studied with respect to the beam intensity and energy distributions, and a close agreement is found between the calculated and experimental results. The intensity is between 10(9) and 10(10) photons s(-1) mm(-2) under typical operating conditions. The harmonic content of a 25 keV beam is about 30% at the minimum wiggler gap of 25 mm (field 1.57 T) and decreases by an order of magnitude when the gap is increased to 60 mm (field 0.62 T). The experimental set-up for CT studies includes dose monitors, goniometers and translation stages for positioning and scanning the object, and a 432-element linear-array Ge detector. Examples from phantom studies and in vivo animal experiments are shown to illustrate the spatial resolution and contrast of the reconstructed images.

Sensitization to the conditioned rewarding effects of morphine and cocaine: differential effects of the kappa-opioid receptor agonist U69593.

The ability of the kappa-opioid receptor agonist U69593 to attenuate the sensitization and cross-sensitization which develops to the conditioned rewarding effects of morphine and cocaine was examined using an unbiased place-preference conditioning procedure. The influence of U69593 treatment upon sensitization and cross-sensitization to cocaine was also assessed. Doses of morphine (1.0-5.0 mg kg(-1)) which failed to produce a conditioned response in drug-naive rats produced marked preferences for the drug-paired place in animals which had previously received once daily injections of morphine (5.0 mg kg(-1); s.c.) or cocaine (10.0 mg kg(-1); i.p.) for 5 days. Morphine-induced place preferences also occurred in animals which had received morphine in combination with U69593 (0.04-0.32 mg kg(-1); s.c.) on either days 3-5 or 1-5 of the morphine treatment regimen. In contrast, morphine failed to produce significant conditioning in animals which had received U69593 with cocaine for 5 days. Doses of cocaine (1.0-5.0 mg kg(-1)) which did not produce a conditioned response in naive rats produced preferences for the drug-paired place in animals which had received once daily injections of cocaine (10.0 mg kg(-1) day(-1) x 5 days; i.p.) or morphine (5.0 mg kg(-1) day(-1) x 5 days; s.c.). No enhancement of cocaine-induced conditioning occurred in animals which had received U69593 on days 3-5 or on days 1-5 of the five-day cocaine treatment. In animals, however, which had received U69593 with morphine for 5 days, an enhanced response to cocaine was still seen. These findings confirm that sensitization and cross-sensitization develop to the conditioned rewarding effects of cocaine and morphine. They also indicate that the ability of a kappa-opioid receptor agonist to prevent the development of these sensitized responses depends on the sensitizing agent employed. U69593 prevents sensitization and cross-sensitization induced by cocaine, but does not modify morphine-induced sensitization or the cross-sensitization which develops to cocaine after morphine administration.