Extrinsic Esophageal Compression by Cervical Osteophytes in Diffuse Idiopathic Skeletal Hyperostosis: A Contraindication to Transesophageal Echocardiography?

Contraindications to transesophageal echocardiography (TEE) include various esophageal pathologies, but compression of the esophagus by vertebral osteophytes is not listed in the current American Society of Echocardiography guidelines. We report a case of diffuse idiopathic skeletal hyperostosis (DISH) in an 81‐year‐old man who had incidentally been found to have extrinsic esophageal compression by cervical osteophytes prior to a proposed TEE. The incidence of esophageal perforation in patients with DISH and vertebral osteophytes is not well documented. We believe these patients are at increased risk of esophageal perforation during TEE, and thus, TEE may be relatively contraindicated in patients with DISH.     

Functional hierarchy underlies preferential connectivity disturbances in schizophrenia

Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined resting-state functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia.Schizophrenia (SCZ) is a disabling psychiatric disease associated with widespread neural disturbances. These involve abnormal neurodevelopment (1–3), neurochemistry (4–7), neuronal gene expression (8–11), and altered microscale neural architecture (2). Such deficits are hypothesized to impact excitation-inhibition (E/I) balance in cortical microcircuits (12). Clinically, SCZ patients display a wide range of symptoms, including delusions, hallucinations (13, 14), higher-level cognitive deficits (15, 16), and lower-level sensory alterations (17). This display is consistent with a widespread neuropathology (18), such as the E/I imbalance suggested by the NMDA receptor (NMDAR) hypofunction model (19–21). However, emerging resting-state functional magnetic resonance imaging (rs-fMRI) studies implicate more network-specific abnormalities in SCZ. Typically, these alterations are localized to higher-order association regions, such as the fronto-parietal control network (FPCN) (18, 22) and the default mode network (DMN) (23, 24), with corresponding disturbances in thalamo-cortical circuits connecting to association regions (25, 26). It remains unknown how to reconcile widespread cellular-level neuropathology in SCZ (20, 21, 27, 28) with preferential association network disruptions (29, 30).Currently a tension exists between two competing frameworks: global versus localized neural dysfunction in SCZ. Association network alterations in SCZ, identified via neuroimaging, may arise from a localized dysfunction (3, 9, 31, 32). Alternatively, they may represent preferential abnormalities arising emergently from a nonspecific global microcircuit disruption (20, 33). Mechanistically, an emergent preferential effect could occur because of intrinsic differences between cortical areas in the healthy brain, leading to differential vulnerability toward a widespread homogenous neuropathology. For example, histological studies of healthy primate brains show interregional variation in cortical cytoarchitectonics (34–38). Additional studies reveal differences in microscale organization and activity timescales for neuronal populations in higher-order association cortex compared with lower-order sensory regions (38–40). However, these well-established neuroanatomical and neurophysiological hierarchies have yet to be systematically applied to inform network-level neuroimaging disturbances in SCZ. In this study, we examined the neuroimaging consequences of cortical hierarchy as defined by neurophysiological criteria (i.e., functional) rather than anatomical or structural criteria.One way to link cellular-level neuropathology hypotheses with neuroimaging is via biophysically based computational models (18, 41). Although these models have been applied to SCZ, none have integrated cortical hierarchy into their architecture. Here we initially implemented elevated E/I ratio within our well-validated computational model of resting-state neural activity (18, 42, 43) without assuming physiological differences between brain regions, but maintaining anatomical differences. The model predicted widespread elevated functional connectivity as a consequence of elevated E/I ratio. In turn, we tested this connectivity prediction across 161 SCZ patients and 164 matched healthy comparison subjects (HCS). However, we discovered an inhomogeneous spatial pattern of elevated connectivity in SCZ generally centered on association cortices.To capture the observed inhomogeneity, we hypothesized that pre-existing intrinsic regional differences between association and lower-order cortical regions may give rise to preferential network-level vulnerability to elevated E/I. Guided by primate studies examining activity timescale differences across the cortical hierarchy (39, 44), we incorporated physiological differentiation across cortical regions in the model. Specifically, we tested whether pre-existing stronger recurrent excitation in “association” networks (39, 40) would preferentially increase their functional connectivity in response to globally elevated E/I. Indeed, modeling simulations predicted preferential effects of E/I elevation in association networks, which could not be explained by structural connectivity differences alone.Finally, we empirically tested all model-derived predictions by examining network-specific disruptions in SCZ. To investigate diagnostic specificity of SCZ effects, we examined an independent sample of bipolar disorder (BD) patients (n = 73) that did not follow model-derived predictions. These results collectively support a parsimonious theoretical framework whereby emergent preferential association network disruptions in SCZ can arise from widespread and nonspecific E/I elevations at the microcircuit level. This computational psychiatry study (45) illustrates the productive interplay between biologically grounded modeling and clinical effects, which may inform refinement of neuroimaging markers and ultimately rational development of treatments for SCZ.     

p53 and Ki-67 in Barrett's carcinoma: is there any value to predict recurrence after circumferential endoscopic mucosal resection?

BACKGROUND: There are situations in which the specimens obtained after endoscopic mucosal resection of superficial adenocarcinoma arising from Barrett's esophagus are not adequate for histopathological assessment of the margins. In these cases, immunohistochemistry might be an useful tool for predicting cancer recurrence. AIM: To evaluate the value of p53 and Ki-67 immunohistochemistry in predicting the cancer recurrence in patients with Barrett's esophagus-related cancer referred to circumferential endoscopic mucosal resection. METHODS: Mucosectomy specimens from 41 patients were analyzed. All endoscopic biopsies prior to endoscopic mucosal resection presented high-grade dysplasia and cancer was detected in 23 of them. Positive reactions were considered the intense coloration in the nuclei of at least 90% of the cells in each high-power magnification field, and immunostaining could be classified as superficial or diffuse according to the mucosal distribution of the stained nuclei. RESULTS: Endoscopic mucosal resection samples detected cancer in 21 cases. In these cases, p53 immunohistochemistry revealed a diffuse positivity for the great majority of these cancers (90.5% vs. 20%), and Ki-67 showed a diffuse pattern for all cases (100% vs. 30%); conversely, patients without cancer revealed a superficial or negative pattern for p53 (80% vs. 9.5%) and Ki-67 (70% vs. 0%). During a mean follow-up of 31.6 months, 5 (12.2%) patients developed six episodes of recurrent cancer. Endoscopic mucosal resection specimens did not show any significant difference in the p53 and Ki-67 expression for patients developing cancer after endoscopic treatment. CONCLUSIONS: p53 and Ki-67 immunohistochemistry were useful to confirm the cancer; however, they had not value for predicting the recurrent carcinoma after circumferential endoscopic mucosal resection of Barrett's carcinoma.     

The pathogenesis and management of disseminated intravascular coagulation

The pathologic and progressive generation of thrombin in human blood can result in the development of disseminated intravascular coagulation (DIC), a syndrome associated with many underlying conditions and manifested as microvascular thrombosis, tissue hypoxia, and organ damage. DIC can be either acute or chronic, with acute DIC resulting from generation of a large amount of thrombin in a brief time period and chronic (compensated) DIC developing as a result of exposure of the coagulation system to small amounts of tissue factor leading to increased but nonacute levels of thrombin generation. DIC can also be considered a thrombohemorrhagic syndrome. Acute DIC at first manifests in a hypercoagulable state and leads to thrombosis, but can be followed by the development of a so-called hypocoagulable phase caused by depletion of clotting factors. This depletion can sometimes lead to bleeding. Bleeding is less common in chronic DIC, as coagulation factors and platelets are more likely to be able to be replenished in the majority of patients. Diagnosis of DIC can sometimes be difficult, depending upon the stage and presentation of the syndrome. During the thrombotic phase of DIC, many common laboratory parameters remain normal, with the important exception of an early drop in circulating platelets. DIC is easier to diagnose when the patient is bleeding, as abnormalities can normally be detected in global coagulation tests and factor assays. Therapy involves identification and treatment of the underlying condition, if possible. In the interim, measures to control bleeding can be administered, if necessary, and may include supportive care with blood products, antithrombin, heparin, and other agents.     

Nurses' perceptions of quality end-of-life care on an acute medical ward

AIM: This paper reports the findings of a study that generated a conceptual model of the nursing behaviours and social processes inherent in the provision of quality end-of-life care from the perspective of nurses working in an acute care setting. BACKGROUND: The majority of research examining the issue of quality end-of-life care has focused on the perspectives of patients, family members and physicians. The perspective of nurses has generally received minimal research attention, with the exception of those working within palliative or critical care. The vast majority of hospitalized patients, however, continue to be cared for and die on medical units. To date, little research has been conducted examining definitions and determinants of quality end-of-life care from the perspective of nurses working in acute adult medical settings. METHOD: Grounded theory method was used in this study of 10 nurses working on acute medical units at two tertiary university-affiliated hospitals in central Canada. Data were collected during 2002 by interview and participant observation. FINDINGS: The basic social problem uncovered in the data was that of nurses striving to provide high quality end-of-life care on an acute medical unit while being pulled in all directions. The unifying theme of 'Creating a haven for safe passage' integrated the major sub-processes into the key analytic model in this study. 'Creating a haven for safe passage' represents a continuum of behaviours and strategies, and includes the sub-processes of 'facilitating and maintain a lane change'; 'getting what's needed'; 'being there'; and 'manipulating the care environment'. CONCLUSION: The ability of nurses to provide quality end-of-life care on an acute medical unit is a complex process involving many factors related to the patient, family, healthcare providers and the context in which the provision of end-of-life care takes place.     

Tobacco addiction and HIV infection: toward the implementation of cessation programs. ANRS CO3 Aquitaine Cohort

In treated HIV-infected patients, mortality is now dominated by non-AIDS-related causes in which tobacco smoking is a predominant risk factor. The implementation of tobacco smoking cessation programs is therefore warranted to increase survival but should consider the specificities of this population to be successful. All outpatients consulting in May to June 2004 within the ANRS CO3 Aquitaine Cohort of HIV-infected patients were asked to complete a self-administered questionnaire including questions about tobacco and other drugs consumption, the Fagerstr?m Test for Nicotine Dependence (FTND), a visual scale to estimate motivation to stop smoking and the Center for Epidemiologic Studies Depression (CESD) scale. Among 509 patients included, mean age was 44 years, 74% were men, 19% were infected through injection drug use, and 257 (51%) were regular smokers (at least one cigarette per day). Among them, 60% had a medium or strong nicotine dependence (FTND = 5), 40% were motivated to quit smoking and 70% had already tried at least once. An FTND of 5 or more was more frequently reported in the 146 smokers (62%) with depressive symptoms compared to other smokers (70% versus 48%). Fifty-five regular smokers (23%) were codependent on cannabis and 31 (12%) to alcohol. Overall, only 35 (14%) regular smokers were motivated, non-codependent, without depressive symptoms, and could be proposed a standard tobacco cessation program. Depressive symptoms were highly prevalent in this representative population of HIV-infected patients. To be successful, smoking cessation interventions should be specifically built to take into account depression and codependencies in addition to nicotine dependence and motivation.     

Predictors of cognitive decline in older individuals with diabetes

OBJECTIVE—The purpose of this study was to determine longitudinal predictors of cognitive decline in older individuals with diabetes who did not have dementia.RESEARCH DESIGN AND METHODS—Cognitive assessments were performed in 205 subjects with diabetes (mean age 75.3 years) and repeated a median 1.6 years later. The sample was drawn from an existing cohort study, and data on diabetes, cardiovascular risk factors, and complications were collected 7.6 ± 1.1 years before and at the time of the initial cognitive assessment. Cognitive status was defined using the Clinical Dementia Rating (CDR) scale, and cognitive decline was defined by change in CDR.RESULTS—The sample included 164 subjects with normal cognition (CDR 0) and 41 with cognitive impairment without dementia (CDR 0.5). At follow-up, 33 (16.1%) had experienced cognitive decline (4 new cases of dementia and 29 cognitive impairment without dementia). Only educational attainment predicted cognitive decline from the data collected 7.6 years before cognitive assessment. Univariate predictors of cognitive decline at the time of the first cognitive assessment included age, education, urinary albumin-to-creatinine ratio (ACR), and treatment with either ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). With multiple logistic regression controlling for age and education, cognitive decline was predicted by natural logarithm ACR (odds ratio 1.37 [95% CI 1.05–1.78], P = 0.021), whereas treatment with either ACEIs or ARBs was protective (0.28 [0.12–0.65], P = 0.003).CONCLUSIONS—In this sample of older patients with diabetes, microalbuminuria was a risk factor for cognitive decline, whereas drugs that inhibit the renin-angiotensin system were protective. These observations require confirmation because of their considerable potential clinical implications.It has been established from longitudinal studies that in older individuals, diabetes is a risk factor for dementia and for cognitive decline (1,2). Recent studies also indicated that older patients with diabetes have an increased risk of having milder degrees of cognitive impairment (3,4). These patients may have a higher-than-normal likelihood of progressing to dementia. Most studies have defined cognitive decline by a change in neurocognitive test scores, and the clinical relevance of this information can be unclear. In addition, there have been few longitudinal studies of the causes of mild cognitive impairment in diabetes.There are many potential mechanisms linking diabetes with cognitive decline. Diabetes is a risk factor for cerebrovascular disease that can cause cognitive impairment due to ischemic brain damage and may directly or indirectly promote Alzheimer''s disease (5,6). In addition, other processes related to diabetes, such as advanced glycation end product accumulation or changes in cerebral insulin signaling, may promote Alzheimer''s disease (7). Identified risk factors for dementia and cognitive decline in diabetes have included hyperglycemia (3,5), insulin therapy (8), duration of diabetes (9,10), and peripheral arterial disease (10). Most identified and possible risk factors are interrelated, and few studies have comprehensively examined all potential explanatory or confounding variables. Microalbuminuria is an independent cardiovascular risk factor of particular relevance in diabetes, and there have been recent reports of inverse associations between microalbuminuria and performance on cognitive tests (11,12).The aim of the present study was to explore cardiovascular risk factors, including microalbuminuria, for clinically relevant cognitive decline in a sample of diabetic patients with dementia who had undergone a comprehensive assessment encompassing a range of relevant variables.     

Disentangling Attentional Biases and Attentional Deficits in Depression: An Event-Related Potential P300 Analysis

Electroencephalographic event-related potentials (ERPs) were used to investigate maladaptive attentional processes in depression. Specifically, we measured the ERP P300 component—a waveform that reflects the real-time allocation of attention to stimuli of high informational salience—as it was elicited by neutral and negatively valent words among currently depressed, previously depressed, and never-depressed participants. The study design allowed us to clarify the degree to which the oft-reported attenuation of P300 response in depression should be regarded as evidence of: (a) a general, pervasive impairment in depressive attentional function; or (b) the operation of depressotypic attentional biases, which may give rise to attentional deficits only regarding stimuli of non-negative emotional valence. Consistent with the latter possibility, depressed individuals were observed in this study to experience, on average, a robust P300 response to negatively valent target words—a response of larger magnitude than that observed among previously depressed and never-depressed controls. This enhanced P300 response to negative stimuli in depression appears to be a statelike, rather than traitlike, phenomenon.

Live three-dimensional echocardiography of the human fetus

The purpose of this study was to investigate the feasibility of using a new three-dimensional ultrasound system to perform fetal echocardiographic examination in real time. The device consisted of a Philips Sonos 7500 (Andover, MA) ultrasound system and a 4 MHz, 4X matrix transducer. The study was approved by the Institutional Review Board and was performed with the informed consent of the mother. The study population consisted of 12 singleton fetuses with gestational ages of 16-37 weeks. Of these, ten fetuses had normal cardiac anatomy, one had complete atrioventricular septal defect, and the other a thickened tricuspid valve. The system allowed comprehensive visualization of fetal cardiac anatomy and color Doppler flow unattainable by two-dimensional approaches. This preliminary investigation suggests that live three-dimensional fetal echocardiography could be a significant tool for prenatal diagnosis and assessment of congenital heart disease in the human fetus.