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We report on a new polymorph of silver antimonate AgSbO 3 discovered with the use of high-pressure high-temperature synthesis at 16 GPa and 1380 °C. The crystal structure is determined from X-ray powder diffraction, and we find this new high-pressure phase crystallizes in monoclinic space group C 2/ c with the following values: a = 8.4570(3) Å, b = 9.8752(3) Å, c = 8.9291(3) Å, β = 91.1750(12)°, and V = 745.56(4) Å 3 . We synthesized the high-pressure (16 GPa) AgSbO 3 phase from the ilmenite phase as a precursor. This high-pressure monoclinic AgSbO 3 consists of a three-dimensional network of corner- and edge-sharing SbO 6 octahedra with channels along the c -direction containing Ag atoms. We also synthesize AgSbO 3 in the defect pyrochlore phase at 4 GPa from the same ilmenite precursor and compare the Raman spectra and the cation-anion bonding of all three AgSbO 3 phases. The absence of a cubic perovskite form of AgSbO 3 even at pressures of ≤16 GPa is likely due to the covalency of the Sb-O bonds and the moderate electronegativity of Ag + . Hybridization of Ag d and O p orbitals results in a variation of Ag-O distances that correlates with the band gap, which is in qualitative agreement with the density of states around the Fermi level from our density functional calculations. We compare AgSbO 3 with other ABX 3 compounds to elucidate the dependence of the structure on the constituent atoms.

Objectives: Tonsillectomy is the most common operation performed by otolaryngologists in the UK, despite this we have a poor understanding of the post-operative recovery. We aimed to investigate post-operative bleeding and pain following paediatric tonsillectomy using a patient diary., Design: Prospective observational cohort study., Setting: Multi-centre study involving 12 secondary and tertiary otolaryngology units across the North of England. Patients were recruited from 1st March 2020 to 30th June 2022. Multilevel ordered logistic regression model statistics were performed., Participants: Children (≥4 years, ≤16 years) undergoing tonsillectomy (with or without adenoidectomy) for benign pathology., Main Outcome Measures: Frequency and severity of post-operative bleeding. Intensity and pattern of post-operative pain., Results: In total 297 children were recruited, with 91 (30.6%) diaries eligible for analysis. Post-operative bleeding occurred in 44% of children. Most frequently blood in the saliva was reported (82.9%). Increasing age significantly increased bleeding odds by 17% per year (p = .001). Bleeding frequency decreased with higher surgeon grade (p = .003) and when performing intracapsular coblation tonsillectomy (p = .02) compared with other techniques. Lower age and intracapsular coblation tonsillectomy, against other techniques, significantly reduced rates of pain post-operatively (p < .0001 and p = .0008)., Conclusion: A high level of low-level post-operative bleeding was observed. Pain scores remained high for 5 days post-operatively then gradually reduce to normal by day 13. Intracapsular coblation tonsillectomy appears to be superior to all other techniques in terms of reducing post-operative bleeding and pain. These findings should be used to guide patients in the consent process to inform them of the expected nature of post-surgical recovery., (© 2023 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Abstract: Addiction is a highly misunderstood and stigmatized chronic illness frequently encountered by health care providers during routine medical care. People with substance use disorders, in particular, face extraordinary stigma and bias when interacting with health care providers, including nurses. Stigma associated with addiction contributes to health inequities and is recognized as a significant barrier to people seeking and receiving necessary health care. Since patients often spend the most time with nurses in the clinical setting, nurses are ideally positioned to address addiction stigma. However, many nurses lack knowledge about addiction, stigma, and the impact of the words they use, whether in conversation or in clinical documentation. This article reviews the consequences of addiction stigma (labeling, stereotyping, or discrimination) and the steps nurses can take to reduce biases related to substance use. A case scenario based on our experience will be used to guide a discussion of opportunities for nurses to intervene and improve care., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Empathy is a core skill essential to patient-centred care. Yet a decline in empathy throughout undergraduate medical education is well recognised. The mainstay of existing teaching approaches to foster medical students' empathic ability has largely focused on the cognitive domain of empathy within the context of communication skills learning. However, there is growing evidence for educational initiatives that better evoke students' affective emotional responses., Approach: A student-led educational initiative was created to enhance medical students' understanding of empathy through undertaking different experiential approaches. Eight medical students were invited to participate in an empathy workshop that involved two experiential approaches: personal simulation, and patient narrative, selected given their expected focus on the affective domain., Evaluation: A subsequent focus group discussion explored students' reactions, learning, and intended future change in practice. Discussions were coded and analysed for descriptive themes. Both initiatives were reported to generate students' empathic responses. Personal simulation evoked more affective domains whilst patient narratives additionally created cognitive empathic insight into the impact of the patient's condition. Students also reported intended changes to their future consulting practices., Conclusions: Although this is a small-scale exploration of medical students' experiences of empathy-related teaching initiatives, it offers insight into how each initiative could target different aspects of empathy. Data support the use of even brief experiential teaching to improve medical students' empathy during their undergraduate training. We provide recommendations for clinical educators who are considering designing similar initiatives within their undergraduate medical curricula., (© 2022 The Authors. The Clinical Teacher published by Association for the Study of Medical Education and John Wiley & Sons Ltd.)

A pilot study was conducted to determine whether 3-monthly groin ultrasonography could eliminate groin dissection after a negative bilateral groin ultrasound in three groups of patients: (i) Those with a unifocal stage 1B squamous cell carcinoma of up to 20 mm in diameter. (ii) Those with an ipsilateral squamous cell carcinoma of any size which extended to within 1 cm either side of the midline. These patients underwent ipsilateral inguinofemoral lymphadenectomy and ultrasonic surveillance of the contralateral groin. (iii) Patients with multifocal invasive lesions with the largest individual focus 20 mm or less in diameter. Three additional patients were added because they either refused groin dissection or were considered unfit for surgery. All ultrasonically positive nodes were confirmed histologically. Thirty-two patients were entered, and no patients were lost to follow-up. Forty-three groins were followed. With a median follow-up of 37 months, three positive nodes (9.4%) were detected. One patient died of her recurrence (3.1%), and 39 groins (90.7%) were preserved. The overall sensitivity of ultrasonic surveillance was 100% (95% CI: 44-100%), with a specificity of 97% (95% CI: 83-99%) and a negative predictive value of 100% (95% CI: 88-100%). This pilot justifies a larger study on serial ultrasonography in lieu of groin dissection in selected patients with vulvar cancer.

Background: Injectable anaesthetic agents, topical creams and aqueous solutions have previously been used to anaesthetise the tympanic membrane for minor ear procedures. Topical creams take 20-30 minutes to work and injectable anaesthetics can cause canal swelling. The effectiveness of lidocaine spray has not previously been investigated in patients undergoing minor ear procedures., Methods: Eighteen participants attending for out-patient grommet insertion or intratympanic steroid injection were prospectively recruited for this study over six months. Post-operatively, they were asked about their perceived level of pain and overall experience., Results: The median level of pain measured on an 11-point visual analogue scale was 2 out of 10. Forty-four per cent reported the overall experience as pleasant, with the remainder selecting slightly unpleasant (66 per cent). All participants stated they would undergo the procedure again., Conclusion: Xylocaine spray is simple to administer, rapid-acting and well tolerated by patients for anaesthesia of the tympanic membrane during minor ear procedures in the out-patient setting.

Objectives: To assess the clinical and cost effectiveness of transnasal oesophagoscopy (TNO) in cases of suspected upper aerodigestive tract malignancy and define its role as a safe alternative to panendoscopy. We have also analysed if the implementation of TNO during the COVID-19 pandemic was beneficial in order to provide uninterrupted care to the patients with the limited resources available in these challenging times., Methods: All patients who underwent TNO guided biopsies or dilatation attempted over a 7 month period during COVID- 19 pandemic were included by searching the hospital and department database at The Royal Albert Edward Infirmary. A comparative group of patients who underwent panendoscopy over 9 months were included for comparison. Demographic data, histological diagnosis, second procedure and cost involved were recorded., Results: During this period, 20 TNO procedures (16 biopsies and 4 dilatations) were attempted which were compared with 20 panendoscopy procedures. The diagnostic accuracy of TNO biopsy for identifying benign and malignant pathology was 81.1%. The sensitivity and specificity for identifying malignancy was 76.9% and 100% respectively. The most common lesion location was laryngeal (43.8%) followed by oropharyngeal (37.5%), more specifically located at the tongue base. The median waiting period between the procedure being listed and TNO being performed was 5.5 days compared to 12 days for panendoscopy. There were 12/16 patients who did not require further interventions for histological diagnosis of the tumor. The TNO procedure was well tolerated with no complications and all were done under local anaesthesia as outpatient procedure without need for admission. TNO resulted in cost saving of £356 per case on a standard NHS tariff., Conclusion: TNO is a valuable diagnostic tool for patients with suspected UADT malignancy and dysphagia and has proven to be an asset during the COVID-19 pandemic when we have to make the best use of the limited theatre time and resources. Also, the cost analysis showed that outpatient based TNO can provide significant cost savings for the current standard of care. Furthermore, it has shown better patient tolerability, lesser complications and shortened the time for diagnosis and hence starting timely treatment for these patients.

Clandestine chemists have demonstrated an ability to convert commercially available pseudoephedrine formulations to methamphetamine. Some of these formulations have properties that manufacturers claim limit or block the extraction of pseudoephedrine and its direct conversion to methamphetamine. In this study, 3 commercially available pseudoephedrine formulations were evaluated for ease of extraction and conversion to methamphetamine using a common chemistry technique called the one-pot method that is frequently employed by clandestine chemists. Two marketed pseudoephedrine formulations with claimed tamper-resistant properties - Zephrex-D ® and Nexafed ® - were compared to Sunmark ® , a comparator formulation of pseudoephedrine without tamper-resistant properties. Particle size reduction was conducted using 8 readily available tools; solubility was assessed using 2 common aqueous solutions and various reaction conditions (e.g., temperature, stirring); extractability was evaluated using 8 common organic solvents. The one-pot (single vessel) method commonly used in clandestine processes was employed; chemicals and equipment were purchased locally on the open market. Quantities and addition times of the chemicals used to carry out the procedure and the duration of the reaction were varied to determine the effect on methamphetamine yield. The procedure was appropriately scaled and conducted in a controlled environment to reduce risk and maximize yields. Pseudoephedrine and methamphetamine were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Standard quantitative procedures were used to determine the quantities of pseudoephedrine and methamphetamine recovered and produced, respectively. Particle size reduction resulted in some loss of material of each pseudoephedrine formulation; Zephrex-D tablets were broken down to a coarse material; Nexafed and Sunmark tablets were reduced to a fine powder. The solubility rates of intact and ground tablets varied by product; Zephrex-D was most resistant to solubilizing while Nexafed and Sunmark were comparable and dissolved completely, demonstrating no solubility-resistant properties. Conditions of the one-pot method were modified throughout the studies to increase methamphetamine yield. Using optimal parameters identified in these studies and allowing the reaction to proceed for 90 min, average percent conversions were similar for the 3 formulations: 43.3% for Zephrex-D, 46.4% for Nexafed, and 48.6% for Sunmark. The greatest conversion occurred with a 150 min reaction time and resulted in 44.8%-48.4% conversion of Zephrex-D, 54.1%-66.4% conversion of Nexafed, and 58.6%-71.8% conversion of Sunmark. This series of methodological evaluations demonstrated that clandestine chemists can readily produce similar yields of methamphetamine using pseudoephedrine products with and without claimed tamper-resistant technology., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

The recently-discovered high pressure material MnFe 3 O 5 displays a rich variety of magnetically ordered states on cooling. Fe spins order antiferromagnetically below a Néel transition at 350 K. A second transition at 150 K marks Mn spin order that leads to spin canting of some of the Fe spins and ferrimagnetism. A further transition at 60 K is driven by charge ordering of Fe 2+ and Fe 3+ over two inequivalent Fe sites, with further canting of all spins. Electrical resistivity measurements reveal semiconducting behaviour in MnFe 3 O 5 with a change in activation energy at 285 K.

A Sr analogue of Ca 0.5 Bi 0.5 FeO 3 , Sr 0.5 Bi 0.5 FeO 3 , containing unusually high valence Fe 3.5+ ions was synthesized by using a high-pressure technique. It relieves the electronic instability due to the unusually high valence of Fe 3.5+ by a single charge disproportionation (CD) transition (Fe 3.5+ → 0.75Fe 3+ + 0.25Fe 5+ ) rather than the successive CD and intermetallic charge transfer (CT) transitions seen in Ca 0.5 Bi 0.5 FeO 3 . Conduction-band narrowing due to the significant bend in the Fe-O-Fe bond in the rhombohedral R3̅c crystal structure stabilized the charge-disproportionated state at low temperatures. Most importantly, Bi 3+ ions in Sr 0.5 Bi 0.5 FeO 3 do not act as countercations accepting oxygen holes as they do in Ca 0.5 Bi 0.5 FeO 3 , resulting in the absence of the intermetallic CT transition. The large cavity of the A-site Sr ions prevents the charge-transferred Bi 5+ from being stabilized. In the charge-disproportionated state the nearest-neighbor Fe 3+ spins align antiferromagnetically and one-fourth of the Fe 3+ spins are randomly replaced by Fe 5+ spins coupled ferromagnetically with the neighboring Fe 3+ spins.

Personally owned handheld referencing technology such as smartphones or tablets, and the adjunct applications (apps) that can be used on them, are becoming a part of everyday life for the New Zealand population. In common with the population at large, student nurses have embraced this technology since the advent of the Apple iPhone in 2010. Little is known internationally or in New Zealand about the way student nurses may apply personally owned handheld referencing technology to their education process. The perceptions of New Zealand nurse managers, toward personally owned handheld referencing technology, could not be located. Using a qualitative descriptive methodology, semi structured interviews were conducted with New Zealand student nurses (n = 13), and nurse managers (n = 5) about their perceptions of use of personally owned handheld referencing technology as an educational tool in clinical settings. A thematic analysis was conducted on the resulting text. Student nurses said they wanted to use their own handheld referencing technology to support clinical decisions. Nurse managers perceived the use of personally owned handheld referencing technology as unprofessional, and do not trust younger cohorts of student nurses to act ethically when using this technology. This research supports historical research findings from the student perspective about the usefulness of older hand held referencing devices to augment clinical decisions. However, due to perceptions held by nurse mangers regarding professional behaviour, safety and the perceived institutional costs of managing personally owned handheld referencing technology, the practice may remain problematic in the studied setting., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The contexts where drugs are self-administered play an important role in regulating persistent drug taking and in relapse to such taking after periods of abstinence. Here, we review the behavioral and brain mechanisms enabling contexts to promote and prevent relapse to drug seeking. We review the key brain structures, their neuropharmacology and their connectivity. We discuss the similarities and differences between the mechanisms for context-induced reinstatement of drug seeking vs. other forms of relapse to drug seeking in animal models and we highlight the numerous deficits in our understanding. We emphasize that current understanding, although significant, defies explanations in terms of models at the level of brain structures and their connectivity. Rather, we show that there is significant functional compartmentalization and segregation within these structures during reinstatement and extinction of drug seeking that parallels their anatomical segregation into circuits and channels. A key challenge is to recognize this complexity, understand how these circuits and channels are organized, as well as understand how different modes of activity of ensembles of neurons within them promote abstinence or relapse to drug seeking., (© 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Intracavity ultrasound transducer handles are not routinely immersed in liquid high-level disinfectants. We show that residual bacteria, including pathogens, persist on more than 80% of handles that are not disinfected, whereas use of an automated device reduces contamination to background levels. Clinical staff should consider the need for handle disinfection.

Background: The short version of the Problem Behaviours Assessment (PBA-s) is the recommended outcome measure for behavioural symptoms in Huntington's disease. Rasch analysis was used to further investigate the measurement limitations of the PBA-s., Objectives: 1) To assess the psychometric properties of the 11 severity and frequency items within the PBA-s and 2) to determine the construct validity of using a total PBA-s score as a clinical outcome measure., Methods: PBA-s data for 517 participants from Enroll-HD were included in the Rasch analysis. Separate analyses were conducted for the severity and frequency items of the PBA-s, using RUMM2030 software. Achieving fit to the model provides supporting evidence that all items contribute to a single underlying latent trait. This property is defined as internal construct validity., Results: The total PBA-s severity score demonstrated several important limitations, including disordered response categories for all 11 severity items, local dependency and poor targeting. However, modifying the original five-point scoring system to a four-point system resulted in ordered response categories for seven of the severity items and achieved a good overall fit to the Rasch model. For the total PBA-s frequency score, fit to the model was not achieved even after amendments to the scoring system., Conclusions: This study suggests that with reduction to a four-point scoring system, the total PBA-s severity score may be considered a valid clinical outcome measure. This study also suggests limitations in the use of a total PBA-s frequency score.

Many clinicians use ultrasound estimates of fetal weight to assess fetal growth. This study assessed the accuracy of the Hadlock IV equation, the equation used at the Royal Hospital for Women, Randwick, NSW, in estimating birth weight. The accuracy of the Hadlock IV equation was assessed based on systematic and random error as well as absolute error. 709 women who underwent ultrasound examination within 8 weeks of delivery between January 2009-May 2011 were included. 305 women underwent ultrasound less than 2 weeks before delivery. The systematic, random and absolute errors of the Hadlock IV equation were -0.47, 27.45 and 8.52%, respectively. This study demonstrates that clinicians may rely on ultrasound estimates of fetal weight performed by well-trained staff in a tertiary institution within 2 weeks of delivery. The accuracy diminishes as the interval between testing and delivery increases. Absolute errors tended to increase with increasing birth weight for all ultrasound-delivery intervals., (© 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: To investigate the effect of uterine adenomyosis diagnosed by transvaginal ultrasound on IVF/ICSI treatment outcome., Study Design: A retrospective cohort study of all women aged ≤ 42 years with infertility who underwent IVF/ICSI treatment at IVF Australia-East between January 2000 and June 2006. Patients were divided into two groups according to findings on a baseline pre-treatment transvaginal pelvic ultrasound: group A consisted of women with adenomyosis and group NA consisted of women without adenomyosis. The primary outcome measure was live birth rate per patient (cycle)., Results: A total of 201 patients (37 patients in Group A, 164 patients in group NA) undergoing a single stimulated cycle of IVF/ICSI were included in the data analysis. There was no difference in live birth rate per patient (cycle) between the two groups with both raw and logistic regression adjusted data (29.7%V 26.1%; p=0.395; OR 1.45 with 95% CI 0.61-3.43). There were no other differences in ovarian response, embryological parameters or clinical outcomes between the two groups., Conclusions: The presence of transvaginal ultrasound diagnosed adenomyosis did not adversely affect outcome in women undergoing IVF/ICSI treatment at our unit. However, the results are not conclusive and further large, well-designed prospective cohort studies are required in order to confirm our findings., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Rats were trained to self-administer cocaine in a distinctive context (context A). They were then extinguished in a second context (context B) prior to test for cocaine-seeking in the original training context, context A (group ABA), context B (group ABB) or no test (group AB0). Group ABA showed renewal of extinguished cocaine-seeking associated with c-Fos induction in basolateral amygdala, lateral hypothalamus, and infralimbic prefrontal cortex. Groups ABA and ABB showed test-associated c-Fos induction in prelimbic prefrontal cortex, nucleus accumbens (core, shell, rostral pole), striatum, lateral amygdala, perifornical hypothalamus, and ventral tegmental area. Double immunofluorescence revealed that renewal-associated c-Fos was expressed in orexin-negative lateral hypothalamic neurons whereas test-associated c-Fos was expressed in orexin-positive perifornical hypothalamic neurons. Retrograde tracing from lateral hypothalamus with cholera toxin revealed only sparse dual-labeled neurons in basolateral amygdala and infralimbic prefrontal cortex, suggesting that these regions contribute to renewal of cocaine-seeking independently of their projections to lateral hypothalamus. Retrograde tracing from the ventral tegmental area suggested that hypothalamic contributions to cocaine-seeking are likewise independent of projections to the midbrain. These results suggest that renewal of cocaine-seeking depends critically on basolateral amygdala, lateral hypothalamus, and infralimbic prefrontal cortex. Whereas basolateral amygdala and lateral hypothalamus contributions may be common to renewal of extinguished cocaine-, alcohol-, and sucrose-seeking, infralimbic prefrontal cortex contributions appear unique to renewal of cocaine-seeking and may reflect the habitual nature of relapse to cocaine.

Transvaginal ultrasound with an empty bladder is recommended as a standardised ultrasonic technique for the accurate diagnosis of the retroverted uterus. Using this method, the prevalence of the retroverted uterus in 480 general gynaecological patients attending for subspecialist gynaecological ultrasound was 18%. The anteverting effect of the full bladder required for transabdominal ultrasound reduces the prevalence of the retroverted uterus to 13% (P < 0.001).

We used an ABA renewal design to study the neural correlates, and role of D1 dopamine receptors, in contextual control over extinguished alcohol-seeking. Rats were trained to respond for 4% beer in one context (A), extinguished in a different (B) context, and then tested for responding in the original training context (A) or the extinction context (B). ABA renewal was mediated by D1 dopamine receptors because it was prevented by SCH23390. ABA renewal of alcohol-seeking was associated with selective increases in c-Fos protein induction in basolateral amygdala, ventral accumbens shell, and lateral hypothalamus (renewal-associated Fos). By contrast, being tested was associated with increased c-Fos induction in anterior cingulate, prelimbic and infralimbic cortex, rostral agranular insula, dorsomedial accumbens shell, and accumbens core (test-associated Fos). Renewal-associated Fos in ventral accumbens shell and lateral hypothalamus, but not basolateral amygdala, was D1 dopamine receptor dependent. Double immunofluorescence showed that renewal-associated Fos was expressed in orexin-negative lateral hypothalamic neurons. However, c-Fos induction in either lateral hypothalamic orexin-negative or orexin-positive neurons was positively and significantly correlated with alcohol-seeking. Test-associated c-Fos induction was observed in orexin-positive perifornical neurons. In both regions, c-Fos expression was dependent on D1 dopamine receptors. These results suggest that renewal of extinguished alcohol-seeking depends on a distributed neural circuit involving basolateral amygdala, ventral accumbens shell, and lateral hypothalamus that involves D1 dopamine receptors. Comparison with our previous results [Hamlin AS, Blatchford KE, McNally GP (2006) Renewal of an extinguished instrumental response: Neural correlates and the role of D1 dopamine receptors. Neuroscience 143:25-38] permits identification of similarities and differences in the correlates of renewal of extinguished drug- and natural-reward seeking.

Contexts play an important role in controlling the expression of extinguished behaviors. We used an ABA renewal design to study the neural correlates, and role of D1 dopamine receptors, in contextual control over extinguished instrumental responding. Rats were trained to respond for a sucrose reward in one context (A). Responding was then extinguished in the same (A) or different (B) context. Rats were tested for responding in the original training context (A). Return to the original training context after extinction (group ABA) was associated with a return of responding. Three distinct patterns of Fos induction were detected on test: 1) ABA renewal was associated with selective increases in c-Fos protein induction in basolateral amygdala, ventral accumbens shell, and lateral hypothalamus (but not in orexin- or melanin-concentrating hormone (MCH)-hypothalamic neurons); 2) being placed in the same context as extinction training (AAA or ABB) was associated with a selective decrease in c-Fos induction in rostral agranular insular cortex; 3) being placed in any context on test was associated with the up-regulation of c-Fos induction in anterior cingulate, dorsomedial accumbens shell, accumbens core, lateral septum, and substantia nigra. The return of responding in ABA renewal was prevented by pre-treatment with the D1 dopamine receptor antagonist SCH23390 (10 microg/kg; s.c.). SCH23390 also suppressed basal and renewal-associated c-Fos protein induction throughout accumbens, and, selectively suppressed renewal-associated c-Fos induction in lateral hypothalamus. These results suggest that renewal of extinguished responding for a sucrose reward depends on a distributed neural circuit involving basolateral amygdala, ventral accumbens shell, and lateral hypothalamus. D1 dopamine receptors within this circuit are essential for renewal. The results also suggest that rostral agranular insular cortex may play an important role in suppressing reward-seeking after extinction training.

Purpose: To examine the relationship between age and ovarian perifollicular blood flow (PFBF) in women undergoing IVF., Methods: Serial transvaginal power Doppler ultrasound (PDU) scans to assess ovarian PFBF were performed prospectively throughout the follicular phase of ovarian stimulation in women undergoing IVF. The ultrasound assessment days were categorized according to day of hCG trigger., Results: A total of 1050 ovarian follicles from 34 women undergoing one IVF treatment cycle were used for data analysis. The median age of the women was 38.5 years, ranging from 28 years to 44 years. There was a significant negative correlation between age and ovarian PFBF on the day of hCG trigger or trigger day minus 1, but not beforehand during the follicular phase., Conclusions: There was a significant negative correlation between age and ovarian PFBF in women undergoing IVF which was only observed very late in the follicular phase of ovarian stimulation.

Objective: To determine whether ovarian perifollicular blood flow (PFBF) in the early follicular phase (EFP) was associated with treatment outcome., Design: Retrospective longitudinal cohort study., Setting: Tertiary referral centre/university hospital., Patients: Thirty-four women underwent 37 IVF cycles, which resulted in 35 embryo transfers., Interventions: Serial transvaginal scans using power Doppler ultrasound during the follicular phase. Ovarian PFBF of follicles > or =5 mm was subjectively assessed using a modified grading system (grades 0-4)., Main Outcome Measures: Ovarian PFBF and pregnancy., Results: Treatment cycles were retrospectively divided into two groups: Group 1 (n=20) had cycles with at least one small (5-10 mm) or medium (11-14 mm) size follicle(s) of high grade (2-4) PFBF on cycle day 5 or 6 or 7; and Group 2 (n=17), had cycles that did not. Group 1 had a significantly higher proportion of high grade large follicles in the late follicular phase (35% vs. 21%) (OR 2.0; 95% CI 1.1-3.7) and higher clinical pregnancy rate (47% vs. 12%) (OR 6.3; CI 1.1-35.7) compared to Group 2., Conclusion: High grade ovarian PFBF in the EFP during IVF is associated with both high grade PFBF in the late follicular phase and a higher clinical pregnancy rate.

Objective: To evaluate whether ovarian perifollicular blood flow (PFBF) varies by ultrasound among women with polycystic and normal ovaries undergoing in vitro fertilization (IVF)., Design: Prospective observational cohort study of women undergoing IVF treatment., Setting: Department of reproductive medicine at a university teaching hospital., Patient(s): Thirty four women with regular spontaneous ovulatory menstrual cycles undergoing IVF divided into two groups according to findings on a baseline transvaginal ultrasound scan: group 1 consisted of 20 women with ultrasound-evident normal ovaries (USNO group), and group 2 consisted of 14 women with ultrasound-evident polycystic ovaries (USPCO group)., Intervention(s): Serial transvaginal power Doppler ultrasound assessments throughout the follicular phase of ovarian stimulation., Main Outcome Measure(s): Ovarian PFBF and ovarian stromal artery pulsatility index., Result(s): Women with USPCO had a significantly lower ovarian stromal artery pulsatility index at the time of the first ultrasound assessment before starting the FSH injections compared with USNO women. However, there was no difference in ovarian PFBF between women with USPCO and USNO during the follicular phase of ovarian stimulation for IVF., Conclusion(s): There is no difference in ovarian follicular vascularity between women with polycystic and normal ovaries during ovarian stimulation at IVF treatment.

Purpose: This longitudinal study aimed to compare ovarian perifollicular and endometrial blood flow (PFBF and EBF, respectively) during the follicular phase in pregnant and non-pregnant IVF cycles., Methods: Serial transvaginal scans were performed in 15 subjects undergoing IVF treatment. Both PFBF and EBF were subjectively graded (grades 0-4 for PFBF and grades 1-3 for EBF). After confirmation of clinical pregnancy, the treatment cycles were grouped into 'Pregnant' and 'Non-pregnant' cycles. Ovarian PFBF and EBF were retrospectively compared between the two groups., Results: In pregnant cycles, the proportion of large (> or = 15 mm) follicles with high (24) grade PFBF increased with time throughout the follicular phase, and the proportion of large follicles with poor (0-1) grade PFBF decreased. In non-pregnant cycles these trends were reversed. There was no difference in EBF between the two groups., Conclusion: The pattern of ovarian PFBF but not EBF may be predictive of treatment outcome.

The authors studied the role of context in reinstatement. Freezing was reinstated when the conditioned stimulus (CS) was extinguished in 1 context and rats moved to another context for reexposure to the shock unconditioned stimulus (US) and test. It was also reinstated (rather than renewed) when rats were shocked in the extinction context and moved to another context for test. This reinstatement was CS specific and reduced by nonreinforced exposures to the extinction context. Rats shocked in the context in which a stimulus had been preexposed froze when tested in another context. These findings suggest 2 roles for context in reinstatement: conditioning of the test context (M. E. Bouton, 1993) and mediated conditioning by the extinction context (P. C. Holland, 1990).

The extra-hypothalamic actions of corticotropin-releasing hormone (CRH) have been accorded an important role in coordinating responses to stressors and contributing to the consequences of drug abuse. Recent proposals suggest that CRH actions in the bed nucleus of the stria terminalis coordinate responses to tonic/unpredictable stressors whereas these actions in the central nucleus of the amygdala coordinate responses to phasic/predictable stressors. We used in situ hybridization histochemistry and site-specific microinjections of a CRH receptor antagonist to study the role of CRH in opiate withdrawal. Rats undergoing opiate withdrawal displayed clear behavioral and autonomic changes accompanied by hyperalgesia and increased plasma corticosterone. In situ hybridization of CRH mRNA revealed significant increases in the central nucleus of the amygdala but not in the bed nucleus of the stria terminalis among rats either chronically pre-treated with morphine, given an injection of naloxone, or both (precipitated withdrawal). An increase of CRH mRNA in the paraventricular nucleus of the hypothalamus was specific to rats undergoing withdrawal. Intracerebroventricular microinjection of the CRH receptor antagonist, alpha(h)CRH(9-41), reduced the severity of opiate withdrawal. Microinjections of alpha(h)CRH(9-41) into the central nucleus of the amygdala also reduced the severity of withdrawal whereas bed nucleus of the stria terminalis microinjections of alpha(h)CRH(9-41) were without effect. These experiments provide evidence for a role of amygdala, but not bed nucleus of the stria terminalis, CRH in opiate dependence. We propose a specific role for down-regulation of opiate receptor signaling in increased expression of the CRH gene in the amygdala. Moreover, we suggest that the roles accorded to CRH in the bed nucleus of the stria terminalis versus amygdala in coordinating responses to stressors may need to be reconsidered to distinguish between external and internal/interoceptive stressors.

Rationale: Pavlovian conditioning processes have been accorded an important role in maintaining persistent opiate administration. At least one locus for this contribution is during opiate withdrawal. These experiments studied the contribution of Pavlovian conditioning processes to morphine withdrawal., Objectives: To determine whether exposure to a distinctive context or odor paired with morphine withdrawal would provoke a withdrawal syndrome, defensive behaviors (e.g., freezing) and pain modulatory (e.g., hypoalgesia) responses similar to those produced by exposure to stimuli signaling other sources of aversive stimulation (e.g., footshock), or whether both withdrawal and fear-like responses would be provoked., Methods: Rats were used in four experiments to study the effects on defensive behavior and pain sensitivity of naloxone-precipitated morphine withdrawal or exposure to a distinctive context or odor previously paired with such withdrawal., Results: Injection of 2.5 mg/kg naloxone in morphine-dependent rats precipitated a withdrawal syndrome characterized by whole body shaking, diarrhea, ptosis, and postural abnormalities (experiment 1). Exposure to either a distinctive context (experiment 2) or odor (experiments 3) previously paired with morphine withdrawal provoked the species-typical defense response of freezing but not signs of withdrawal. Exposure to an odor previously paired with morphine withdrawal also provoked hypoalgesia in the formalin test, which was mediated by activity at opioid receptors (experiment 4)., Conclusions: These results show that opiate withdrawal supports the conditioning of defensive and hypoalgesic responses consistent with the arousal of a fear motivational system. The emergence of fear in these experiments, and the relationship between the freezing observed here and the learned avoidance and suppression observed in other withdrawal conditioning preparations, is discussed with reference to dual representation accounts of Pavlovian conditioning.

We used the tail-flick response of rats to study the role of opioid receptors in illness-induced hyperalgesia. An intraperitoneal injection of lithium chloride (LiCl) produced hyperalgesia that was blocked in a dose-dependent manner by subcutaneous injection of the opioid antagonist naloxone. Neither hyperalgesia nor its blockade by naloxone were due to variations in tail-skin temperature induced by LiCl. Hyperalgesia was also blocked when opioid receptor antagonism was restricted to (a) the periphery, by intraperitoneal administration of the quaternary opioid receptor antagonist naloxone methiodide; (b) the brain, by intracerebroventricular microinjection of naloxone; or (c) the spinal cord, by intrathecal microinjection of naloxone. These results document a pain facilitatory role of opioid receptors in both the peripheral and central nervous systems and are discussed with reference to their analgesic and motivational functions.

Rationale: Pairings of a sweet taste and injection of morphine result in a learned avoidance of that taste and learned analgesic tolerance. This avoidance is mediated by the drug's peripheral effect, while learned tolerance involves activation of N-methyl-D-aspartate (NMDA) receptors. Exposure to a sweet taste also reduces morphine analgesia. We studied whether this taste-mediated reduction was reversed by an NMDA or peripheral opioid receptor antagonist., Objectives: To determine whether an intraoral infusion of saccharin would modulate morphine analgesia in rats, and to study the contribution of NMDA as well as peripheral opioid receptors to this modulation., Methods: Six experiments used the rat's tail-flick response to study the effect of an intraoral infusion of a sodium saccharin solution on morphine analgesia, and the effects of the quaternary opioid receptor antagonist methylnaltrexone as well as the noncompetitive NMDA receptor antagonist MK-801 on this modulation of analgesia., Results: An intraoral infusion of saccharin reduced the analgesic effects of an intraperitoneal (i.p.) injection of morphine across a range of doses (experiment la), which was not attributable to an influence on tail-skin temperature (experiment 1b). This reduction was mediated by opioid receptors in the periphery and activation of NMDA receptors because morphine analgesia was reinstated by an i.p. injection of either methylnaltrexone (experiment 2a) or MK-801 (experiment 3a), which was not due to the effect of methylnaltrexone (experiment 2b) or MK-801 (experiment 3b) on morphine analgesia in the absence of saccharin., Conclusions: These results document evidence for an antagonism of morphine analgesia by actions of the drug at peripheral opioid receptors and excitatory amino-acid activity at NMDA receptors. They are discussed with reference to the aversive motivational effects of peripheral opioid receptors and pain facilitatory circuits.

Sensitivity to noxious stimulation is not invariant; rather, it is modulated by discrete pain inhibitory and facilitatory circuits. This paper reviews the neural circuits for pain facilitation, describes the conditions governing their environmental activation, and examines their role in an animal's behavioral repertoire. Mechanisms for pain facilitation are contrasted at both the neural and behavioral level with mechanisms for pain inhibition. In addition, the involvement of mechanisms for pain facilitation in morphine analgesic tolerance is discussed, and the implications of this involvement for accounts of the role of associative processes in analgesic tolerance are highlighted.

The hyperalgesic properties of the emetic drug lithium chloride (LiCl) were examined in eight experiments. At a dose of 63.6 mg/kg, LiCl produced hyperalgesia in the radiant-heat (Experiment la) and immersion (Experiment 1b) tail-flick tests. At doses of 15.9, 31.8, 63.6, and 127.2 mg/kg, LiCl failed to produce hyperalgesia during the delayed behavioral response in the formalin test (Experiments 2a and 2b), but 63.6 mg/kg LiCl did produce hyperalgesia during the normally quiescent, interphase period of formalin responding (Experiment 2c). At the dose of 63.6 mg/kg, LiCl did not produce hyperalgesia in the hotplate test (Experiments 3a and 3b) and did not exert significant motoric effects in a step-down passive-avoidance task (Experiment 4). The results were discussed with reference to the behavioral effects of LiCl and their implications for demonstrations of associatively mediated morphine analgesic tolerance.

A flavor paired with morphine shifted to the right the function relating morphine dose to tail-flick latencies and provoked hyperalgesic responses when rats were tested in the absence of morphine. These learned increases in nociceptive sensitivity were not mediated by alterations in tail-skin temperature. Microinjection of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP-5) into the lateral ventricle reversed the hyperalgesic responses but spared the tolerance to morphine analgesia. By contrast, systemic administration of the noncompetitive NMDA receptor antagonist MK-801 or intrathecal infusion of AP-5 reversed the hyperalgesic responses as well as the tolerance to morphine analgesia. The results demonstrate that associatively mediated tolerance to morphine analgesia can co-occur with hyperalgesic responses and are discussed relative to learned activation of endogenous pronociceptive mechanisms.

To investigate the compliance of family members with the treatment recommended for patients, three child and adolescent psychiatrists assessed the charts of all active outpatients in a developmental disabilities clinic in the psychiatric department of a tertiary care municipal hospital utilizing a Family Compliance Checklist, a survey form for chart review, in October, 1993 (n = 40), and in April, 1994 (n = 41). Almost no clients missed appointments over a 6-mo. period. Only one family refused to permit the use of medication. Three families refused to make appointments. The majority of the patients were Hispanic and almost half were Roman Catholic. We conclude that most families of patients in a developmental disabilities clinic comply with recommended treatment plans including scheduled appointments and prescribed medications.

In this study, the levels of the cysteine proteinase--cathepsin B were measured in diseased synovial fluids using a steady state fluorometric assay. Cathepsin B-like activity was shown to be present in all the samples analysed, with the rheumatoid arthritic synovial fluids possessing significantly higher concentrations (mean value ca. 416 mg/l) than the osteoarthritic fluids (mean value ca. 142.4 mg/l). In addition, upon treatment with pepsin, all of the rheumatoid arthritis samples were shown to possess additional cathepsin B-like activity, suggesting the presence of a reservoir of latent precursor molecules. By utilising a recently developed biotinylated affinity label for cathepsin B-like proteinases and sheep anti-(human cathepsin B) antibodies, used in combination with SDS-PAGE and Western blotting, the rheumatoid arthritic synovial cathepsin B was shown to exist in two forms with apparent molecular masses of M(r) 29,000 and 42,000. We propose that the former is a functionally active proteinase, whereas the latter is a pepsin activatable proform which, when cleaved by this aspartyl proteinase, is converted into a catalytically competent species of M(r) 20,000.

1. A 1H-n.m.r. method was used to measure concentrations of valine, alanine, lactate, acetate, hyaluronan and lipids in synovial fluid obtained, during the normal course of examination from the knee joints of patients attending rheumatology and orthopaedic clinics. Fluid was available from 16 patients with osteoarthritis, 18 patients with rheumatoid arthritis, four patients with meniscal tear and one patient each with systemic lupus erythematosis, mono-arthritis, synovitis and loose bodies. Four normal specimens were obtained for comparison. 2. Valine, alanine and acetate levels all showed a normal Gaussian distribution, reflecting the distributions within the serum of the sample population. 3. Lactate concentrations divided into two distinct patterns. At concentrations below 2.5 mmol/l the lactate levels showed a Gaussian distribution, reflecting the distribution in normal serum. The normal synovial fluid specimens belong to this distribution. Above 2.5-3.0 mmol/l, lactate levels were asymmetric in distribution with a long tail at higher concentrations. These high levels of lactate can be explained by the generation of lactate through anaerobic metabolism within the synovial cavity. This metabolic process is triggered by a general inflammatory condition such as in rheumatoid arthritis. 4. The distribution of n.m.r.-observable lipid concentrations in rheumatoid arthritis and osteoarthritis each shows a normal distribution and the mean concentration is significantly higher in rheumatoid arthritis. 5. An increased n.m.r.-observable hyaluronan concentration is associated with an inflammatory situation. 6. It is concluded that raised levels of lactate and n.m.r.-observable hyaluronan and lipids are useful markers to aid the clinical distinction between rheumatoid arthritis and osteoarthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

The Shuttle Experiment conducted between Hawaii and Tahiti from January 1979 to June 1980 was designed to observe the changing equatorial ocean structure and circulation, to study the variations and interactions of the four major equatorial ocean currents, and to develop a scientific basis for their monitoring by simple observations of thermal structure and sea level. Preliminary analyses of the results show that the equatorial thermal structure remains intact during a normal year and that only the positions and intensities of the currents are subject to change. The water transport of the equatorial undercurrent varied from 25 x 10(6) cubic meters per second in January to 51 x 10(6) cubic meters per second in July, but also exhibited strong short-term pulsations. The equatorial surface flow responded strongly to the winds at periods of 1 month and longer. An array of drifter buoys in the equatoral countercurrent was subject to very little dispersion while traveling over 4500 kilometers in 4 months. Low-frequency fluctuations in the North Equatorial Countercurrent can be monitored by means of the difference in sea level between Fanning and Majuro.