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Background: Intravenous magnesium (IV Mg), a commonly utilized therapeutic agent in the management of atrial fibrillation (AF) with rapid ventricular response, is thought to exert its influence via its effect on cellular automaticity and prolongation of atrial and atrioventricular nodal refractoriness thus reducing ventricular rate. We sought to undertake a systematic review and meta-analysis of the effectiveness of IV Mg versus placebo in addition to standard pharmacotherapy in the rate and rhythm control of AF in the nonpostoperative patient cohort given that randomized control trials (RCTs) have shown conflicting results., Methods: Randomized controlled trials comparing IV Mg versus placebo in addition to standard of care were identified via electronic database searches. Nine RCTs were returned with a total of 1048 patients. Primary efficacy endpoints were study-defined rate control and rhythm control/reversion to sinus rhythm. The secondary endpoint was patient experienced side effects., Results: Our analysis found IV Mg in addition to standard care was successful in achieving rate control (odd ratio [OR] 1.87, 95% confidence interval [CI] 1.13-3.11, p = .02) and rhythm control (OR 1.45, 95% CI 1.04-2.03, p = .03). Although not well reported among studies, there was no significant difference between groups regarding the likelihood of experiencing side effects., Conclusions: IV Mg, in addition to standard-of-care pharmacotherapy, increases the rates of successful rate and rhythm control in nonpostoperative patients with AF with rapid ventricular response and is well tolerated., (© 2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi-institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty-two patients were identified with median age of 11 years. Thirty-three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety-one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty-six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow-up time was 36 months. Overall 5-year survival was 95% and 5-year event-free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted., (© 2022 UICC.)

Background: Patients admitted to hospital with acute heart failure (AHF) are at increased risk of readmission and mortality post-discharge. The aim of the study was to examine health service utilisation within 30 days post-discharge from an AHF hospitalisation., Methods: This was a prospective, observational, non-randomised study of consecutive patients hospitalised with acute HF to one of 16 Victorian hospitals over a 30-day period each year and followed up for 30 days post-discharge. The project was conducted annually over three consecutive years from 2015 to 2017., Results: Of the 1,197 patients, 56.3% were male with an average age of 77±13.23 years. Over half of the patients (711, 62.5%) were referred to an outpatient clinic and a third (391, 34.4%) to a HF disease management program. In-hospital mortality was 5.1% with 30 day-mortality of 9% and readmission rate of 24.4%. Patients who experienced a subsequent readmission less than 10 days post-discharge and between 11 and 20 days post-discharge had a five- to six-fold increase in risk of mortality (adjusted OR 5.02, 95% CI 2.11-11.97; OR 6.45, 95% CI 2.69-15.42; respectively) compared to patients who were not readmitted to hospital. An outpatient appointment within 30 days post-discharge significantly reduced the risk of 30-day mortality by 81% (95% CI 0.09-0.43)., Conclusion: Patients admitted to hospital with AHF who experience a subsequent readmission within 20 days post-discharge are at increased risk of dying. However, early follow-up post-discharge may reduce this risk. Early post-discharge follow-up is vital to address this vulnerable period after a HF admission., (Copyright © 2020 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Atrial fibrillation (AF) is well-recognized in the pathophysiology of left atrial thrombogenesis and resultant cardioembolic stroke. Subclinical AF is believed to account for a significant proportion of embolic stroke. However, recent randomized control trials failed to demonstrate a significant benefit for oral anticoagulation, in an unselected population with embolic stroke of undetermined source. This has reinvigorated the focus on finding robust markers to identify patients at risk of cardioembolic stroke. Several nonfibrillatory atrial electrical markers, along with structural and biochemical abnormalities, have been associated with ischemic stroke, independently of AF. An increasingly complex relationship exists among vascular risk factors, atrial remodeling, and thrombogenesis. Identifying robust markers of an underlying atrial myopathy may allow for early identification of patients at risk for cardioembolic stroke. This review outlines the inconsistencies in the evidence for AF as the prerequisite for left atrial thrombogenesis and embolic stroke. It will highlight the current evidence and controversies for adverse atrial remodeling, independent from rhythm, as a plausible mechanism for left atrial thrombogenesis and ischemic stroke., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Genetic variants associated with primary open-angle glaucoma (POAG) are known to influence disease risk. However, the clinical effect of associated variants individually or in aggregate is not known. Genetic risk scores (GRS) examine the cumulative genetic load by combining individual genetic variants into a single measure, which is assumed to have a larger effect and increased power to detect relevant disease-related associations., Objective: To investigate if a GRS that comprised 12 POAG genetic risk variants is associated with age at disease diagnosis., Design, Setting, and Participants: A cross-sectional study included individuals with POAG and controls from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) study. A GRS was formulated using 12 variants known to be associated with POAG, and the alleles associated with increasing risk of POAG were aligned in the case-control sets. In case-only analyses, the association of the GRS with age at diagnosis was analyzed as an estimate of disease onset. Results from cohort-specific analyses were combined with meta-analysis. Data collection started in August 2012 for the NEIGHBOR cohort and in July 2008 for the GLAUGEN cohort and were analyzed starting in March 2018., Main Outcomes and Measures: Association of a 12 single-nucleotide polymorphism POAG GRS with age at diagnosis in individuals with POAG using linear regression., Results: The GLAUGEN study included 976 individuals with POAG and 1140 controls. The NEIGHBOR study included 2132 individuals with POAG and 2290 controls. For individuals with POAG, the mean (SD) age at diagnosis was 63.6 (9.8) years in the GLAUGEN cohort and 66.0 (13.7) years in the NEIGHBOR cohort. For controls, the mean (SD) age at enrollment was 65.5 (9.2) years in the GLAUGEN cohort and 68.9 (11.4) years in the NEIGHBOR cohort. All study participants were European white. The GRS was strongly associated with POAG risk in case-control analysis (odds ratio per 1-point increase in score = 1.24; 95% CI, 1.21-1.27; P = 3.4 × 10-66). In case-only analyses, each higher GRS unit was associated with a 0.36-year earlier age at diagnosis (β = -0.36; 95% CI, -0.56 to -0.16; P = 4.0 × 10-4). Individuals in the top 5% of the GRS had a mean (SD) age at diagnosis of 5.2 (12.8) years earlier than those in the bottom 5% GRS (61.4 [12.7] vs 66.6 [12.9] years; P = 5.0 × 10-4)., Conclusions and Relevance: A higher dose of POAG risk alleles was associated with an earlier age at glaucoma diagnosis. On average, individuals with POAG with the highest GRS had 5.2-year earlier age at diagnosis of disease. These results suggest that a GRS that comprised genetic variants associated with POAG could help identify patients with risk of earlier disease onset impacting screening and therapeutic strategies.

Objective: Recent anticoagulation trials in all-comer cryptogenic stroke patients have yielded equivocal results, reinvigorating the focus on identifying reproducible markers of an atrial myopathy. We investigated the role of excessive premature atrial complexes (PACs) in ischaemic stroke, including cryptogenic stroke and its association with vascular risk factors., Methods and Results: A case-control study was conducted utilising a multicentre institutional stroke database to compare 461 patients with an ischaemic stroke or transient ischaemic attack (TIA) with a control group consisting of age matched patients without prior history of ischaemic stroke/TIA. All patients underwent 24-hour Holter monitoring during the study period and atrial fibrillation was excluded. An excessive PAC burden, defined as ≥200 PACs/24 hours, was present in 25.6% and 14.7% (p<0.01), of stroke/TIA and control patients, respectively. On multivariate regression, excessive PACs (OR 1.97; 95% CI 1.29 to 3.02; p<0.01), smoking (OR 1.58; 95% CI 1.06 to 2.36; p<0.05) and hypertension (OR 1.53; 95% CI 1.07 to 2.17; p<0.05) were independently associated with ischaemic stroke/TIA. Excessive PACs remained the strongest independent risk factor for the cryptogenic stroke subtype (OR 1.95; 95% CI 1.16 to 3.28; p<0.05). Vascular risk factors that promote atrial remodelling, increasing age (≥75 years, OR 3.64; 95% CI 2.08 to 6.36; p<0.01) and hypertension (OR 1.54; 95% CI 1.01 to 2.34; p<0.05) were independently associated with excessive PACs., Conclusions: Excessive PACs are independently associated with cryptogenic stroke and may be a reproducible marker of atrial myopathy. Prospective studies assessing their utility in guiding stroke prevention strategies may be warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Several ECG markers are postulated to represent underlying atrial remodelling and have been associated with ischemic stroke. P-wave terminal force in lead V 1 (PTFV 1 ) is one such marker. We examined the factors that contribute to the reliability of PTFV 1 and its association with ischemic stroke., Material and Methods: Four hundred and thirty-five patients that presented with an ischemic stroke or transient ischemic attack (TIA) were identified through a prospectively maintained multi-site institutional stroke database. Control group consisted of age matched patients without prior history of an ischemic stroke or TIA. All patients underwent a 12-lead ECG and 24-hour Holter monitoring during the study period to exclude atrial fibrillation., Results: Morphology consistent with PTFV 1 occurred commonly in both the stroke/TIA and control groups. There was no significant difference in the median PTFV 1 value between the stroke 3.96 mV ms [Interquartile range (IQR) 2.78-5.58] and control 4.23 mV ms [IQR 2.91-5.57] groups. Measurements of PTFV 1 demonstrated excellent intra-observer reliability on assessment of the same P-wave (Intra class correlation (ICC) 0.91, p < 0.001) with narrow limits of agreement 2.21 to -2.95 mV ms. A change in the P wave assessed led to a significant reduction in reliability (ICC 0.79, p < 0.001). Inter-observer, inter P-wave assessment demonstrated further reduction in reliability (ICC 0.68, p < 0.002) with wide limits of agreement 6.17 to -5.78 mV ms, indicating significant under and overestimation of PTFV 1 ., Conclusion: The utility of PTFV 1 as a clinical marker for ischemic stroke is limited by the reduction in reliability associated with inter-observer and inter P-wave measurements., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Noncoding microRNAs (miRNAs) have been implicated in the pathogenesis of glaucoma. We aimed to identify common variants in miRNA coding genes (MIR) associated with primary open-angle glaucoma (POAG)., Methods: Using the NEIGHBORHOOD data set (3853 cases/33,480 controls with European ancestry), we first assessed the relation between 85 variants in 76 MIR genes and overall POAG. Subtype-specific analyses were performed in high-tension glaucoma (HTG) and normal-tension glaucoma subsets. Second, we examined the expression of miR-182, which was associated with POAG, in postmortem human ocular tissues (ciliary body, cornea, retina, and trabecular meshwork [TM]), using miRNA sequencing (miRNA-Seq) and droplet digital PCR (ddPCR). Third, miR-182 expression was also examined in human aqueous humor (AH) by using miRNA-Seq. Fourth, exosomes secreted from primary human TM cells were examined for miR-182 expression by using miRNA-Seq. Fifth, using ddPCR we compared miR-182 expression in AH between five HTG cases and five controls., Results: Only rs76481776 in MIR182 gene was associated with POAG after adjustment for multiple comparisons (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.11-1.42, P = 0.0002). Subtype analysis indicated that the association was primarily in the HTG subset (OR = 1.26, 95% CI: 1.08-1.47, P = 0.004). The risk allele T has been associated with elevated miR-182 expression in vitro. Data from ddPCR and miRNA-Seq confirmed miR-182 expression in all examined ocular tissues and TM-derived exosomes. Interestingly, miR-182 expression in AH was 2-fold higher in HTG patients than nonglaucoma controls (P = 0.03) without controlling for medication treatment., Conclusions: Our integrative study is the first to associate rs76481776 with POAG via elevated miR-182 expression.

Purpose: We examined the role of DNA copy number variants (CNVs) of known glaucoma genes in relation to primary open angle glaucoma (POAG)., Methods: Our study included DNA samples from two studies (NEIGHBOR and GLAUGEN). All the samples were genotyped with the Illumina Human660W&#95;Quad&#95;v1 BeadChip. After removing non-blood-derived and amplified DNA samples, we applied quality control steps based on the mean Log R Ratio and the mean B allele frequency. Subsequently, data from 3057 DNA samples (1599 cases and 1458 controls) were analyzed with PennCNV software. We defined CNVs as those ≥5 kilobases (kb) in size and interrogated by ≥5 consecutive probes. We further limited our investigation to CNVs in known POAG-related genes, including CDKN2B-AS1, TMCO1, SIX1/SIX6, CAV1/CAV2, the LRP12-ZFPM2 region, GAS7, ATOH7, FNDC3B, CYP1B1, MYOC, OPTN, WDR36, SRBD1, TBK1, and GALC., Results: Genomic duplications of CDKN2B-AS1 and TMCO1 were each found in a single case. Two cases carried duplications in the GAS7 region. Genomic deletions of SIX6 and ATOH7 were each identified in one case. One case carried a TBK1 deletion and another case carried a TBK1 duplication. No controls had duplications or deletions in these six genes. A single control had a duplication in the MYOC region. Deletions of GALC were observed in five cases and two controls., Conclusions: The CNV analysis of a large set of cases and controls revealed the presence of rare CNVs in known POAG susceptibility genes. Our data suggest that these rare CNVs may contribute to POAG pathogenesis and merit functional evaluation., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

This historical research aimed to develop an accurate perception of the role of spirituality and religion within the history of Alcoholics Anonymous. Primary and secondary sources were reviewed. The study identified that Bill W. and Dr. Bob established the format for the support group based on the ideas of William James, which formed the base for the Oxford Groups. Alcoholics Anonymous was clearly viewed as a spiritual group and not a religion. The review also showed that the two founders had each experienced one of the two types of spiritual awakenings that James had addressed. These findings will help nurses clarify their own perceptions of this organization so they may accurately educate individuals who they are encouraging to participate in this program while recovering from an addiction.

Purpose: Circulating estrogen levels are relevant in glaucoma phenotypic traits. We assessed the association between an estrogen metabolism single nucleotide polymorphism (SNP) panel in relation to primary open angle glaucoma (POAG), accounting for gender., Methods: We included 3,108 POAG cases and 3,430 controls of both genders from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium genotyped on the Illumina 660W-Quad platform. We assessed the relation between the SNP panels representative of estrogen metabolism and POAG using pathway- and gene-based approaches with the Pathway Analysis by Randomization Incorporating Structure (PARIS) software. PARIS executes a permutation algorithm to assess statistical significance relative to the pathways and genes of comparable genetic architecture. These analyses were performed using the meta-analyzed results from the GLAUGEN and NEIGHBOR data sets. We evaluated POAG overall as well as two subtypes of POAG defined as intraocular pressure (IOP) ≥22 mmHg (high-pressure glaucoma [HPG]) or IOP <22 mmHg (normal pressure glaucoma [NPG]) at diagnosis. We conducted these analyses for each gender separately and then jointly in men and women., Results: Among women, the estrogen SNP pathway was associated with POAG overall (permuted p=0.006) and HPG (permuted p<0.001) but not NPG (permuted p=0.09). Interestingly, there was no relation between the estrogen SNP pathway and POAG when men were considered alone (permuted p>0.99). Among women, gene-based analyses revealed that the catechol-O-methyltransferase gene showed strong associations with HTG (permuted gene p≤0.001) and NPG (permuted gene p=0.01)., Conclusions: The estrogen SNP pathway was associated with POAG among women.

With the increased use of engineered nanomaterials such as ZnO and CeO₂ nanoparticles (NPs), these materials will inevitably be released into the environment, with unknown consequences. In addition, the potential storage of these NPs or their biotransformed products in edible/reproductive organs of crop plants can cause them to enter into the food chain and the next plant generation. Few reports thus far have addressed the entire life cycle of plants grown in NP-contaminated soil. Soybean ( Glycine max ) seeds were germinated and grown to full maturity in organic farm soil amended with either ZnO NPs at 500 mg/kg or CeO₂ NPs at 1000 mg/kg. At harvest, synchrotron μ-XRF and μ-XANES analyses were performed on soybean tissues, including pods, to determine the forms of Ce and Zn in NP-treated plants. The X-ray absorption spectroscopy studies showed no presence of ZnO NPs within tissues. However, μ-XANES data showed O-bound Zn, in a form resembling Zn-citrate, which could be an important Zn complex in the soybean grains. On the other hand, the synchrotron μ-XANES results showed that Ce remained mostly as CeO₂ NPs within the plant. The data also showed that a small percentage of Ce(IV), the oxidation state of Ce in CeO₂ NPs, was biotransformed to Ce(III). To our knowledge, this is the first report on the presence of CeO₂ and Zn compounds in the reproductive/edible portion of the soybean plant grown in farm soil with CeO₂ and ZnO NPs.

Background: The PTEN tumour suppressor gene and PIK3CA proto-oncogene encode proteins which contribute to regulation and propagation of signal transduction through the PI3K/AKT signalling pathway. This study investigates the prevalence of loss of PTEN expression and mutations in both PTEN and PIK3CA in colorectal cancers (CRC) and their associations with tumour clinicopathological features, lifestyle factors and dietary consumptions., Methods: 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for PTEN and PIK3CA mutations by DNA sequencing and PTEN expression changes by immunohistochemistry. Dietary and lifestyle data were collected prospectively using seven day food diaries and lifestyle questionnaires., Results: Mutations in exons 7 and 8 of PTEN were observed in 2.2% of CRC and PTEN loss of expression was identified in 34.9% CRC. Negative PTEN expression was associated with lower blood low-density lipoprotein concentrations (p = 0.05). PIK3CA mutations were observed in 7% of cancers and were more frequent in CRCs in females (p = 0.04). Analysis of dietary intakes demonstrated no link between PTEN expression status and any specific dietary factor. PTEN expression negative, proximal CRC were of more advanced Dukes' stage (p = 0.02) and poor differentiation (p < 0.01). Testing of the prevalence of PIK3CA mutations and loss of PTEN expression demonstrated that these two events were independent (p = 0.55)., Conclusion: These data demonstrated the frequent occurrence (34.9%) of PTEN loss of expression in colorectal cancers, for which gene mutations do not appear to be the main cause. Furthermore, dietary factors are not associated with loss of PTEN expression. PTEN expression negative CRC were not homogenous, as proximal cancers were associated with a more advanced Dukes' stage and poor differentiation, whereas distal cancers were associated with earlier Dukes' stage.

Inverted tako-tsubo cardiomyopathy (TTC) is a variation of stress cardiomyopathy. It features transient myocardial dysfunction characterised by a typical contractile abnormality consisting of extensive left ventricular circumferential dyskinesia or akinesia with a hyperkinetic apex. Endogenous catecholamine surges are believed to be the mediators of this potentially life-threatening condition. We describe a patient who received an inadvertent bolus of noradrenaline and developed significant haemodynamic instability associated with electrocardiographic and cardiac biomarkers indicative of diffuse myocardial injury and echocardiography findings of an "inverted" TTC. The patient made a full recovery. Our case highlights that a reversible inverted TTC may result from an exogenous catecholamine surge.

Background: BRAF and K-ras proto-oncogenes encode components of the ERK signalling pathway and are frequently mutated in colorectal cancer. This study investigates the associations between BRAF and K-ras mutations and clinicopathological, lifestyle and dietary factors in colorectal cancers., Methods: 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for BRAF and K-ras mutations. Diet and lifestyle data were collected prospectively using seven day food diaries., Results: BRAF V600E mutation was found in 15.6% of colorectal cancers but at higher frequencies in cancers with proximal location, poor differentiation and microsatellite instability (MSI) (all p < 0.001). K-ras mutation (mostly in codons 12 and 13) was found in 22.0% of colorectal cancers but at higher frequencies in cancers of more advanced Dukes' stage (p = 0.001), microsatellite stable (MSS) status (p = 0.002) and in individuals with lower blood high-density lipoprotein concentrations (p = 0.04). Analysis of dietary factors demonstrated no link between BRAF mutation and any specific dietary constituent, however, K-ras mutation was found at higher frequencies in individuals with higher white meat consumption (p < 0.001). Further analysis of specific mutation type demonstrated that G to A transitions in K-ras were observed at higher frequencies in individuals consuming lower amounts of fruit (p = 0.02)., Conclusion: These data support the model of BRAF and K-ras mutations arising in distinct colorectal cancer subsets associated with different clinicopathological and dietary factors, acting as mutually exclusive mechanisms of activation of the same signalling pathway.

The purpose of this paper is to describe the results of a survey of advanced practice nurses (APNs) to determine the activities they perform related to caring for patients with addictions and or co-occurring mental health disorders, the amount of addictions education in their graduate programs, and their perceptions of the value of addictions education for their role. Data were obtained from 233 APNs in New York State using a tool adapted from a previous job analysis survey. APNs reported the greatest amount of experience in history taking for various types of addictions and co-occurring mental health disorders and least amount of experience in performing objective exams, using standardized screening tools, ordering related diagnostic tests, prescribing pharmacological treatments, and making referrals for addiction treatment. Respondents reported a mean of less than three hours addictions education in their graduate programs in contrast to their high perceived importance of this clinical area.

AKT activity has been reported in the epidermis associated with keratinocyte survival and differentiation. We show in developing skin that Akt activity associates first with post-proliferative, para-basal keratinocytes and later with terminally differentiated keratinocytes that are forming the fetal stratum corneum. In adult epidermis the dominant Akt activity is in these highly differentiated granular keratinocytes, involved in stratum corneum assembly. Stratum corneum is crucial for protective barrier activity, and its formation involves complex and poorly understood processes such as nuclear dissolution, keratin filament aggregation, and assembly of a multiprotein cell cornified envelope. A key protein in these processes is filaggrin. We show that one target of Akt in granular keratinocytes is HspB1 (heat shock protein 27). Loss of epidermal HspB1 caused hyperkeratinization and misprocessing of filaggrin. Akt-mediated HspB1 phosphorylation promotes a transient interaction with filaggrin and intracellular redistribution of HspB1. This is the first demonstration of a specific interaction between HspB1 and a stratum corneum protein and indicates that HspB1 has chaperone activity during stratum corneum formation. This work demonstrates a new role for Akt in epidermis.

Human papillomaviruses (HPVs) are DNA tumour viruses that induce hyperproliferative lesions in cutaneous and mucosal epithelia. The relationship between HPV and non-melanoma skin cancer (NMSC) is important clinically since NMSC is the most common form of malignancy among fair-skinned populations. It is well established that solar ultraviolet (UV) irradiation is the major risk factor for developing NMSC, but a pathogenic role for HPV in the development of NMSC has also been proposed. Recent molecular studies reveal a likely role for HPV infection in skin carcinogenesis as a co-factor in association with UV. This review summarizes the literature describing these data, highlights some of the important findings derived from these studies, and speculates on future perspectives., (Copyright 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background: Recently, we have demonstrated that cyclic variation in ultrasonic integrated backscatter (IBS) can be used to predict patency of the infarct related artery (IRA) post-acute myocardial infarction (AMI). Second harmonic imaging has become widely available on ultrasound machines and enhances endocardial definition. The effect of harmonic imaging on the measurement and interpretation of cyclic IBS is unknown., Methods and Results: Twenty-eight patients were studied post-AMI. Cyclic IBS was measured in myocardial segments supplied by the IRA as well as in remote segments with normal myocardial function in both fundamental and second harmonic modes. Harmonic imaging increased the measurement of cyclic IBS in IRA as well as normal myocardial territories. However, the difference in cyclic IBS between IRA and normal myocardial territories remained unchanged., Conclusion: Second harmonic imaging increases the measurement of cyclic IBS. However, the interpretation of these data is unchanged in the setting of AMI. It is important that repeated studies in the same patient are performed in the same mode (fundamental or harmonic) as the values are not interchangeable.

Background: Brain natriuretic peptide (BNP) is increasingly recognized as a practical, reliable and accurate indicator of left ventricular function and may have an important prognostic role in determining outcome following myocardial infarction and heart failure., Methods and Results: We studied a total of 60 patients referred for dobutamine-stress echocardiography to evaluate possible reversible myocardial ischaemia. There was no echocardiographic evidence of structural or functional heart disease in any of the patients included in the study. Blood was sampled for BNP at rest, prior to dobutamine-stress. We found a significant linear correlation between BNP concentrations and patients' age, in the absence of structural or functional heart disease (r(s) = 0.53, 95% CI 0.25-0.73, P<0.0001)., Conclusion: Our observations suggest the need for consideration of patient's age when interpreting BNP concentrations in the population.

Background: The aim of the present study was to determine the use of cyclic variation in ultrasonic integrated backscatter (IBS), which is reduced in ischemic myocardium, to predict an occluded infarct-related artery (IRA) after thrombolysis for acute myocardial infarction (AMI). This is important, because patency of the IRA 90 minutes after thrombolysis has been shown to predict outcome., Methods and Results: One hundred thirteen patients with AMI had peak-to-peak cyclic IBS measured in the myocardial territory supplied by their IRA as well as a remote territory with normal function from the parasternal long- or short-axis view. This analysis took 5 to 10 minutes. Wall motion score index was assessed, and coronary angiography, to determine patency of the IRA, was performed in all patients. Cyclic IBS in the IRA territory was much lower in segments supplied by an occluded IRA (3.3 versus 4.6 dB, P<0.00001). Using a difference in cyclic IBS between infarcted and normal segments of 15% (or 1.5 dB) as a cutoff, the sensitivity, specificity, positive and negative predictive values to determine an occluded IRA were 92%, 75%, 81%, and 89%, respectively., Conclusions: The difference in cyclic IBS between IRA and remote normal segments, which can be analyzed rapidly, can be used to predict patency of the IRA in patients with AMI. This provides a noninvasive method to determine those patients who may require urgent invasive investigation.

Use of the Amplatzer Septal Occluder device to close selected secundum atrial septal defects is ever-increasing. This article illustrates the central role of the echocardiologist before, during, and after percatheter closure with the Amplatzer Septal Occluder device. Figures, diagrams, and tables detail each stage of the evaluation, procedure, and postprocedural assessment.

During deployment of an Amplatzer atrial septal occluder device to close a secundum ASD, the right atrial disk and waist of the device twisted, resulting in the cobrahead malformation. Postulated mechanisms for this complication include twisting of the device during loading into the delivery catheter and catching of leading edge of the device on the LA free wall or appendage, causing twisting during deployment. Retrieval of the device into the catheter and even removal of the device from the patient to allow manual untwisting may be required to allow the device to return to its original conformation for successful redeployment.

Use of per-catheter atrial septal defect closure devices is becoming increasingly widespread. We report a case of left atrial thrombus formation on a StarFLEX device raising concerns regarding the general use of these devices and as a means of preventing paracloxical embolism in particular.

Transthoracic echocardiography (TTE) has an important role in the assessment of patients with acute penetrating chest trauma. We report the case of a 36-year-old man who sustained a stab wound to the chest. After admission, he required emergency pericardiocentesis. TTE revealed a traumatic ventricular septal defect and a defect in the anterior mitral valve leaflet. To assess whether these lesions were related to the initial stab wound or the pericardiocentesis, the transducer was positioned over the stab wound, and the lesions were shown to be in the same plane as the entry site, thus ruling out iatrogenic trauma.

The Chiari network is a fenestrated membrane consisting of threads and strands in the right atrium. First described in 1897 by anatomist Hans Chiari, it is a congenital remnant of embryonic development resulting from incomplete resorption of the right valve of the sinus venosus. Found in 2% to 3% of the population, it is generally not of clinical importance. Rarely, however, the network may be associated with serious complications such as thrombus formation, embolus entrapment, arrhythmia, tumor development, and catheter entrapment. We report the entanglement of an Amplatzer septal occluder device catheter in a prominent Chiari network that was herniated into the left atrium. Transesophageal echocardiographic recognition of this before deployment and guidance during disentanglement is described below.

An Atlantic white-sided dolphin (Lagenorhynchus acutus), a pygmy sperm whale (Kogia breviceps), 2 harbor seals (Phoca vitulina) developed raised, firm, erythematous, cutaneous nodules that were most prominent on their heads, trunks, and on the caudal portions of their bodies. Prior to the onset of the condition, all 4 animals may have been stressed by factors such as being stranded on a beach, being transported long distances, or being relocated locally. Microbial culturing of the lesions on multiple media yielded fungal isolates containing conidia characteristic of Fusarium spp. Hyphae consistent with those of an ascomycete were evident on histologic examination of lesions. In each treated animal, the dermatitis resolved 3 to 4 weeks after completing treatment with ketoconazole. Fusarium spp may be opportunistic invaders of the skin of marine mammals that have decreased immunocompetence or integumentary compromise.

Objective: The efficacy of buspirone in controlling self-injurious behavior was examined in five individuals with mental retardation. Buspirone was used alone in two individuals and as an adjunct to thioridazine in the other three., Method: Standard behavioral observation methods were used to collect data on the number of self-injurious responses of the individuals during baseline and several doses of buspirone in an open trial., Results: When compared with baseline levels, all five individuals showed some response to buspirone, with reductions in self-injury ranging from 13% to 72%, depending on the dose. The most effective dose of buspirone was 30 mg/day for three individuals and 52.5 mg/day for the other two. These individuals were maintained for 6 to 33 weeks on their most effective dose. Coexistent symptoms of anxiety did not predict a favorable response to buspirone therapy., Conclusions: Buspirone showed a mixed but generally favorable response in controlling intractable self-injury in this and four previous studies reporting similar cases. However, the drug should not be endorsed as a proved treatment for self-injury until similar results have been obtained from well-controlled studies of its efficacy.

Descending thoracic aortic aneurysms are a rare cause of symptomatic airway or esophageal obstruction. We report the case of a patient with simultaneous severe dyspnea and dysphagia from the thoracic portion of a thoracoabdominal aortic aneurysm. Perioperative management of the airway obstruction was an essential component of successful treatment. Repair of the aneurysm resulted in resolution of the patient's symptoms.

Dysfunction of the serotonergic system has been implicated in the development and maintenance of self-injury in some persons with mental retardation. Several preliminary reports have suggested that fluoxetine, a drug that blocks the reuptake of serotonin, may decrease self-injury in these individuals. Of the 44 cases of self-injury treated with fluoxetine and previously reported in the literature, 42 demonstrated a beneficial response to the drug. We report four additional cases of adults with mental retardation whose self-injury was treated with fluoxetine. Each of these individuals benefited from fluoxetine to some extent, with average decreases in self-injury ranging from 20% to 88% when compared with baseline levels. These findings, combined with those from previously published case studies, emphasize the need for well-controlled studies to more adequately assess the effects of fluoxetine on self-injury.

Computed tomography is widely used in the investigation of patients in whom bronchiectasis is suspected, despite considerable variation in its reported sensitivity and specificity. The findings with 3 mm high resolution computed tomography were compared at segmental level with bronchography by two radiologists independently in 27 patients (aged 20-67 years) undergoing investigation of chronic sputum production. Fifteen patients were found to have bronchiectasis by both investigations. Five were identified by computed tomography alone, including two in whom disease was revealed in segments underfilled at bronchography. The sensitivity of computed tomography compared with bronchography in the diagnosis of bronchiectasis at segmental level was 84% and the specificity 82%. The predictive value of computed tomography in the diagnosis of bronchiectasis was 38% overall, but increased to 75% when only those segmental bronchi moderately or severely dilated on the computed tomography scan were considered. There was no relation between the degree of bronchial wall thickening on the computed tomogram and the diagnosis of bronchiectasis by bronchography. Bronchography may be avoided in patients being considered for surgical resection of their bronchiectasis in whom computed tomography shows diffuse disease.

The accuracy of mammography alone and in combination with clinical examination and aspiration cytology was assessed in 402 patients who attended the Early Diagnostic Unit of the Royal Marsden Hospital, London. The sensitivities of mammography, clinical examination and cytology in identifying breast cancer were 76.9%, 81.7% and 63.5% respectively; the specificities of each test were 90.0%, 87.6% and 99.3%. The calculated sensitivity was increased to 96.2% if one positive test out of the three was regarded as an indication to undertake breast biopsy. If this approach was adopted the number of breast cancers missed would be two out of 104 and the yield of positive biopsies would be approximately one in four (27.6%). The implications of proceeding to breast biopsy on the basis of a single positive test are discussed.

The mammograms of 444 patients who had a breast biopsy leading to a definitive histological diagnosis were reviewed. In 21 cases (4.7%) grouped microcalcifications were identified as the only mammographic abnormality. These groups of microcalcifications were analysed to determine whether there was any quantitative difference between benign and malignant lesions with respect to a shape parameter of the group, the spatial frequency of the particles and neighbour-to-neighbour relationships of the particles. This analysis did not reveal any significant difference between the spatial relationships of the grouped microcalcifications found in benign and malignant breast disease.

Large amounts of injected radiolabeled low density lipoproteins have been found by others to accumulate primarily in the liver and studies in various types of isolated cells, including hepatocytes, have indicated the presence of specific cell membrane recognition sites for lipoproteins. In the present studies, the high affinity binding of radiolabeled low density lipoproteins ([125I]LDL, d 1.020--1.063 g/mL) was measured in the major subcellular fractions of porcine liver homogenates. The nuclear and mitochondrial fractions were 1.9- and 1.4-fold enriched in binding activity with respect to unfractionated homogenates and contained 15% and 12% of the total binding activity, respectively. The microsomes, which contained most of the plasma membranes and endoplasmic reticulum, were approximately 4-fold enriched in binding and contained 73% of the binding activity. Microsomal subfractions obtained by differential homogenization and centrifugation procedures were 5.6--7.0-fold enriched in LDL binding and contained 54--58% of the homogenate binding activity. They were separated by discontinuous sucrose density gradient centrifugation into fractions which contained "light" and "heavy" plasma membranes and endoplasmic reticulum. The heavy membrane fraction was 2--4 fold in binding with respect to the parent microsomes (16--22 fold with respect to the homogenate). There was no enrichment of binding activity in the other two fractions. Two plasma membrane "marker" enzymes, nucleotide pyrophosphatase and 5'-nucleotidase, were also followed. Of the two, binding in the sucrose density gradient subfractions most closely followed nucleotide pyrophosphatase, which was also most highly enriched (3.2--3.3-fold) in the heavy membrane fraction, but did not follow it exactly. The enzyme was 2-fold richer in the light membranes than in the parent microsomes, though the light membrane binding activity was only 0.4--1.4 times that of the parent microsomes. High affinity binding was time and temperature dependent, saturable, and inhibited by unlabeled low density lipoproteins but not by unrelated proteins. Binding was stimulated 2--3 fold Ca2+, was not affected by treatment with Pronase or trypsin and was inhibited by low concentrations of phospholipids and high density lipoproteins (HDL). Heparin-Mn2+ treatment of HDL did not affect its ability to inhibit [125I] LDL binding. The LDL recognition site was distinct from the liver membrane asialoglycoprotein receptor; LDL binding was not inhibited by desialidated fetuin. We conclude that porcine liver contains a high affinity binding site that recognizes features common to both pig low density and high density lipoproteins. Further studies may elucidate the significance of this binding site in lipoprotein metabolism.

These experiments compared the effect of a five-day course (days - 1 to +3) of cyclosporine therapy coupled with pretransplant (day - 1) administration of donor-specific antigen (whole blood or splenocytes) on either pancreatic or heart allograft survival in the Buffalo to Lewis rat donor-recipient combination. CsA therapy alone significantly (P less than 0.001) prolonged both heart (16.2 +/- 1.6 days) and pancreas (12.5 +/- 1.5 days) graft survival when compared with nonimmunosuppressed control heart and pancreas grafts (7.7 +/- 1.8 and 7.9 +/- 1.0 days, respectively). Pretransplant transfusion with either 2 ml of BUF whole blood or 2 x 10(8) red cell-free splenocytes on day -1 also resulted in a significant (P less than 0.001) prolongation of heart survival (14.0 +/- 1.2 and 14.0 +/- 1.6 days, respectively) but did not improve pancreas allograft survival (9.4 +/- 1.5 and 8.5 +/- 1.0 days, respectively). Combination CsA and antigen therapy further improved heart graft survival to 26.5 +/- 6.1 days (whole blood) and 28.8 +/- 5.8 days (splenocytes) but did not improve pancreas graft survival over that of CsA therapy alone. Extension of CsA therapy by adding two additional 3-day cycles on days 10-12 and 17-19 further improved heart graft survival both after CsA alone (35.2 +/- 3.2 days) and after CsA coupled with whole-blood transfusion (45.3 +/- 8.6 days), but did not have a salutary effect on pancreas allograft survival. Portal vein administration of donor antigen was equally effective as systemic inoculation in prolonging heart graft survival when the splenocytes were given alone (11.6 +/- 1.7 days). Conversely, pancreas allograft survival was not beneficially effected by portal antigen administration whether or not CsA was given. These data demonstrate the ability of pretransplant donor-specific antigen administration and short-term CsA therapy to significantly prolong rat heart allograft survival across a strong MHC histocompatibility barrier-but, surprisingly, they also demonstrate the failure of this regimen to have a salutary effect on pancreas allograft survival.

Computed tomography is well established in the management of patients with malignant disease, both as a staging procedure before initiation of treatment and in follow up. The presence of unsuspected metastases may affect the decision to perform surgery on the primary tumour and may alter the management of suspected recurrent tumour. Two cases are presented of patients with primary carcinoma whose computed tomography images showed multiple focal hepatic lesions suggestive of metastases. However multiple biliary hamartomas were found on histology, in one case by biopsy and in the other at post mortem. The differential diagnosis and significance of multiple liver defects on computed tomography is considered.

The consequences of an undiagnosed pneumothorax can be life-threatening, particularly in patients with trauma to the head or multiple injury and in those requiring mechanical ventilation. Yet it is these patients, whose films will be assessed initially by the surgeon, who are more likely to have a chest X-ray taken in the supine position. The features of supine pneumothoraces are described and discussed together with radiological techniques used to confirm the diagnosis, including computed tomography (CT) which may be of particular importance in patients with associated cranial trauma.