Aortoesophageal fistula complicating carcinoma involving the esophagus

Summary Three patients manifesting an unusual complication of cancer in the esophagus have been presented. Cases 1 and 2 were instances of primary carcinoma of the esophagus, while Case 3 represents metastases in the esophageal wall from a primary focus in the cervix. All had massive hematemesis associated with perforation of the aorta secondary to local spread of the tumor. The diagnosis in the first 2 patients was unsuspected antemortem, but an aortoesophageal fistula was considered as a source of bleeding at the time of esophagoscopic examination in the third patient. Hemorrhage from the aorta into the esophagus was the cause of death in all 3 patients. The literature pertaining to aortoesophageal fistulas was briefly reviewed.     

Suicidality among military-connected adolescents in California schools

Previous research indicates that suicidal ideation is higher among military-connected youth than non military-connected youth. This study extends prior work by examining suicidal ideation, plans, and attempts in military-connected and non military-connected adolescents. Data were gathered from 390,028 9th and 11th grade students who completed the 2012–2013 California Healthy Kids Survey. Bivariate comparisons and multivariate logistic analyses were conducted to examine differences in suicidal ideation, plans, attempts, and attempts requiring medical attention between military and not military-connected youth. In multivariate logistic analyses, military-connected youth were at increased risk for suicidal ideation (OR = 1.43, 95 % CI = 1.37–1.49), making a plan to harm themselves (OR = 1.19, CI = 1.06–1.34), attempting suicide (OR = 1.67, CI = 1.43–1.95), and an attempted suicide which required medical treatment (OR = 1.71, CI = 1.34–2.16). These results indicate that military-connected youth statewide are at a higher risk for suicidal ideation, plans, attempts, and attempts requiring medical care because of suicidal behaviors. It is suggested that policies be implemented to increase awareness and screening among primary care providers, school personnel, and military organizations that serve military-connected youth.     

Blood Pressure and Fibrinogen Responses to Mental Stress as Predictors of Incident Hypertension over an 8-Year Period

Background

Heightened blood pressure (BP) responses to mental stress predict raised BP levels over subsequent years, but evidence for associations with incident hypertension is limited, and the significance of inflammatory responses is uncertain.

Purpose

We investigated the relationship between BP and plasma fibrinogen responses to stress and incident hypertension over an average 8-year follow-up.

Method

Participants were 636 men and women (mean age 59.1 years) from the Whitehall II epidemiological cohort with no history of cardiovascular disease and hypertension. They performed standardized behavioral tasks (color/word conflict and mirror tracing), and hypertension was defined by clinic measures and medication status.

Results

Of participants in the highest systolic BP reactivity tertile, 29.3 % became hypertensive over the follow-up period compared with 16.5 % of those in the lowest tertile, with an odds ratio of 2.02 (95 % CI 1.17–3.88, p?=?0.012) after adjustment for age, sex, grade of employment, body mass index, smoking, alcohol consumption, physical activity, follow-up time, subjective stress response, perceived task difficulty, perceived task engagement, and baseline BP. Similar associations were observed for diastolic BP reactivity (odds ratio 2.05, 95 % CI 1.23–3.40, p?=?0.006) and for impaired systolic BP post-stress recovery (odds ratio 2.06, 95 % CI 1.19–3.57, p?=?0.010). Fibrinogen reactions to tasks also predicted future hypertension in women (odds ratio 2.64, 95 % CI 1.11–6.30, p?=?0.029) but not men.

Conclusions

These data suggest that heightened cardiovascular and inflammatory reactivity to mental stress is associated with hypertension risk, and may be a mechanism through which psychosocial factors impact on the development of hypertension.

     

Impaired glucose tolerance and metabolic syndrome in idiopathic neuropathy

Idiopathic neuropathy is one of the most common clinical problems encountered in general medical and neurological practices, accounting for up to 40% of all neuropathies in referral series. Several groups have reported an elevated prevalence of impaired glucose tolerance (IGT) in idiopathic neuropathy subjects, although the only carefully conducted case-control study suggested hypertriglyceridemia was a more important risk factor. The nature of the relationship between IGT and neuropathy is a subject of active debate. An evolving literature suggests metabolic syndrome, particularly dyslipidemia and obesity, are potent neuropathy risk factors for both idiopathic and diabetic neuropathy patients. Once established, diabetic neuropathy is likely to be very difficult to reverse. IGT-associated neuropathy, however, may be more amenable to therapy and could represent an ideal population in which to examine potential therapies for diabetes and obesity related neuropathies. Further research is needed to better define the epidemiological relation between IGT, metabolic syndrome, and neuropathy, its underlying pathophysiology, and to develop appropriate surrogate measures and clinical trials strategies.     

In Vivo MicroRNA Detection and Quantitation in Cerebrospinal Fluid

Alterations in microRNA (miRNA) expression in postmortem brain tissue or peripheral blood have been linked to schizophrenia. Cerebrospinal fluid might provide an in vivo biomarker more directly reflecting functional changes in the brain. The goals of this study were to determine the feasibility of detecting miRNAs in cerebrospinal fluid and to compare miRNA levels in cerebrospinal fluid versus blood. Four healthy volunteers and four patients with psychotic disorders underwent a lumbar puncture and a blood draw. Expression of 378 validated miRNAs was assessed from each biofluid type for each subject using microarray technology. Five miRNAs were chosen for validation with quantitative polymerase chain reaction. A substantial number of miRNAs (n?=?95) were exclusively or predominately detected in cerebrospinal fluid (CSF). Levels of 35 miRNAs detected in both CSF and blood samples in all subjects were poorly correlated. The investigation of miRNAs in CSF can help advance the understanding of psychiatric diseases and particularly schizophrenia.     

Identification of SPARC-like 1 protein as part of a biomarker panel for Alzheimer's disease in cerebrospinal fluid

We have used proteomic fingerprinting to investigate diagnosis of Alzheimer's disease (AD). Samples of lumbar cerebrospinal fluid (CSF) from clinically-diagnosed AD cases (n = 33), age-matched controls (n = 20), and mild cognitive impairment (MCI) patients (n = 10) were used to obtain proteomic profiles, followed by bioinformatic analysis that generated a set of potential biomarkers in CSF samples that could discriminate AD cases from controls. The identity of the biomarker ions was determined using mass spectroscopy. The panel of seven peptide biomarker ions was able to discriminate AD patients from controls with a median accuracy of 95% (sensitivity 85%, specificity 97%). When this model was applied to an independent blind dataset from MCI patients, the intensity of signals was intermediate between the control and AD patients implying that these markers could potentially predict patients with early neurodegenerative disease. The panel were identified, in order of predictive ability, as SPARC-like 1 protein, fibrinogen alpha chain precursor, amyloid-β, apolipoprotein E precursor, serum albumin precursor, keratin type I cytoskeletal 9, and tetranectin. The 7 ion ANN model was further validated using an independent cohort of samples, where the model was able to classify AD cases from controls with median accuracy of 84.5% (sensitivity 93.3%, specificity 75.7%). Validation by immunoassay was performed on the top three identified markers using the discovery samples and an independent sample cohort which was from postmortem confirmed AD patients (n = 17).     

Transcriptional profiling of whole blood and serum protein analysis of mice exposed to the neurotoxin Pacific Ciguatoxin-1

Ciguatoxins (CTX) are a suite of cyclic polyether toxins produced by the marine dinoflagellate Gambierdiscus sp., are potent activators of voltage-gated sodium channels and a leading cause of human poisoning from food fish. This report characterizes the genomic and proteomic response in whole blood of adult male mice exposed i.p. to 264 ng/kg of the Pacific congener of CTX (P-CTX-1) at 1, 4 and 24h. Whole genome microarray expression data were filtered by tightness of fit between replicates, fold change (1.8) and p-value (10(-5)), resulting in 183 annotated genes used for trending analysis, K-means clustering and ontology classification. Genes involved with cytokine signaling, proteasome complex and ribosomal function were dominant. qPCR performed on 19 genes of interest had a correlation of 0.95 to array results by Pearson's correlation coefficient. Serum protein analysis showed small but significant changes in 6 of 60 proteins assayed: Ccl2, Ccl12, CD40, IL-10, leptin and M-CSF. In large part, the gene expression was consistent with a Th2 immune response with interesting similarities to expression seen in asthmatic models.     

Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

OBJECTIVE: The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. METHODS: Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. RESULTS: Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. CONCLUSIONS: Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. SIGNIFICANCE: Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.