Faculty Bibliography

OBJECTIVE: : The course of lung function in community members exposed to World Trade Center (WTC) dust and fumes remains undefined. We studied longitudinal spirometry among patients in the WTC Environmental Health Center (WTCEHC) treatment program. METHODS: : Observational study of 946 WTCEHC patients with repeated spirometry measures analyzed on the population as a whole and stratified by smoking status, initial spirometry pattern, and WTC-related exposure category. RESULTS: : Improvement in forced vital capacity (54.4 mL/yr; 95% confidence interval, 45.0 to 63.8) and forced expiratory volume in 1 second (36.8 mL/yr; 95% confidence interval, 29.3 to 44.3) was noted for the population as a whole. Heavy smokers did not improve. Spirometry changes differed depending on initial spirometry pattern and exposure category. CONCLUSION: : These data demonstrate spirometry improvement in select populations suggesting reversibility in airway injury and reinforcing the importance of continued treatment.

BACKGROUND: The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning. To test and validate its methods, the workgroup reviewed data for thallium (Tl). METHODS: After an extensive search, the co-chairs reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Blinded votes were compiled, returned, and discussed during a conference call. A second vote determined the final recommendations. RESULTS: Forty-five articles met inclusion criteria. Only case reports and case series were identified, yielding a very low quality of evidence for all recommendations. Data on 74 patients, including 11 who died, were abstracted. The workgroup concluded that Tl is slightly dialyzable and made the following recommendations: ECTR is recommended in severe Tl poisoning (1D). ECTR is indicated if Tl exposure is highly suspected on the basis of history or clinical features (2D) or if the serum Tl concentration is >1.0 mg/L (2D). ECTR should be initiated as soon as possible, ideally within 24-48 hours of Tl exposure (1D), and be continued until the serum Tl concentration is <0.1 mg/L for a minimal duration of 72 hours (2D). CONCLUSION: Despite Tl's low dialyzability and the limited evidence, the workgroup strongly recommended extracorporeal removal in the case of severe Tl poisoning.

Brain-machine interfaces (BMIs) rely on decoding neuronal activity from a large number of electrodes. The implantation procedures, however, do not guarantee that all recorded units encode task-relevant information: selection of task-relevant neurons is critical to performance but is typically performed based on heuristics. Here, we describe an algorithm for decoding/classification of volitional actions from multiple spike trains, which automatically selects the relevant neurons. The method is based on sparse decomposition of the high-dimensional neuronal feature space, projecting it onto a low-dimensional space of codes serving as unique class labels. The new method is tested against a range of existing methods using simulations and recordings of the activity of 1592 neurons in 23 neurosurgical patients who performed motor or speech tasks. The parameter estimation algorithm is orders of magnitude faster than existing methods and achieves significantly higher accuracies for both simulations and human data, rendering sparse decoding highly attractive for BMIs.

Posterior tongue defects present a unique reconstructive challenge. The various reconstructive options available for treating the defect created by a posterior hemiglossectomy frequently result in a distorted tongue and functional impairment. This paper describes a novel sliding anterior hemitongue flap to allow reconstruction of moderate resection defects (i.e. for T1-T2 tongue squamous cell carcinomas) of the posterior tongue. By mobilizing the anterior tongue, near normal mobility and tongue length are maintained. This surgical technique may be performed alone intraorally or in combination with a neck dissection.

Purpose: Normal neuronal activity is tightly linked to and depends on the increase of blood flow for instantaneous supply of oxygen and glucose. This study is to evaluate whether there are cerebral blood flow (CBF) regulation abnormalities in MS with measurement of cerebrovascular reactivity (CVR) using hypercapnia perfusion MRI. Materials and Methods: Sixteen patients with MS (14 relapsing remitting and 2 secondary progressive) (mean age: 45.1+14.2 years, mean EDSS: 2.9+1.6) and age-matched 13 healthy controls (mean age: 44.5+12.2 years) were recruited for this study. CO2 is a potent vasodilator, and an increase of CO2 tension in blood (referred to as hypercapnia) is known to cause CBF increase. Such CBF changes were measured with a standard pseudo-continuous arterial spin labeling (pCASL) MRI at 3T, with quantitative CBF (ml/min/100g) maps generated during both room air and hypercapnia (mixed 5%CO2, 21%O2, and 74%N2) exposure. The imaging parameters of pCASL include TR/TE=3950/17ms, 52 repetitions, FOV=22cm, in-plane matrix=64x64, slice thickness=5mm, labeling duration=1500ms, postlabeling delay=1230ms, and label location = 84mm below AC-PC line. End-tidal CO2 (EtCO2) was recorded continuously during the scan with a capnograph device and was used as an input function in the analysis. The CVR was calculated as (% change in CBF comparing CO2 inhalation to room-air breathing) divided by (EtCO2 during CO2 inhalation - EtCO2 during room-air breathing). Segmented whole brain grey matter (GM), white matter (WM), and brain parenchymal CVR were calculated for the group analysis. Results: The averaged CVR (%CBF/mmHg EtCO2) showed significant difference for whole brain parenchymal (P=0.009), GM (P=0.008), and WM (P=0.03) between patients (4.74+0.88%, 4.89+1.08%, and 4.73+1.02%) and healthy controls (3.46+1.51%, 3.51+1.47%, and 3.53+1.83%, respectively). There was a significant correlation between brain parenchymal CVR and EDSS (r=-0.69, P=0.007). Whole brain CVR changes correlate with fractional brain p!

The neuroimaging literature on attention-deficit/hyperactivity disorder (ADHD) is growing rapidly. Here, we provide a critical overview of neuroimaging studies published recently, highlighting perspectives that may be of relevance for clinicians. After a comprehensive search of PubMed, Ovid, Web of Science, and EMBASE, we located 41 pertinent papers published between January 2011 and April 2012, comprising both structural and functional neuroimaging studies. This literature is increasingly contributing to the notion that the pathophysiology of ADHD reflects abnormal interplay among large-scale brain circuits. Moreover, recent studies have begun to reveal the mechanisms of action of pharmacological treatment. Finally, imaging studies with a developmental perspective are revealing the brain correlates of ADHD over the lifespan, complementing clinical observations on the phenotypic continuity and discontinuity of the disorder. However, despite the increasing potential to eventually inform clinical practice, current imaging studies do not have validated applications in day-to-day clinical practice. Although novel analytical techniques are likely to accelerate the pace of translational applications, at the present we advise caution regarding inappropriate commercial misuse of imaging techniques in ADHD.

Metabolic syndrome is a condition that typically includes central obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension. Disruption of the hypothalamic-pituitary-adrenal axis, a regulator of corticosterone secretion, occurs in some cases of metabolic syndrome and obesity, and Cushing hypercortisolemia is associated with obesity and metabolic disorders. We therefore assessed anatomic and clinical pathology in C57BL/6NCrl mice to evaluate the effects of chronic corticosterone in the drinking water at doses of 25, 50, and 100 mug/mL for 25 d. Treated mice developed obesity, glucose intolerance, electrolyte aberrations, and dyslipidemia that were dose-dependent and most severe in the 100-mu;g/mL treatment group. To evaluate return to normal function, additional C57BL/6NCrl mice received corticosterone-free water for 2 wk after the 25-d treatment period. According to results of gross examination, mice appeared to recover within days of exogenous corticosterone withdrawal; however, adrenal gland vacuolation and protein, lipid, and electrolyte abnormalities persisted. Together, these findings support chronic corticosterone exposure through the drinking water as a potentially useful, noninvasive method to induce some features of metabolic syndrome.

Drinking pure water markedly increases blood pressure in patients with chronic autonomic failure because water-induced hypo-osmolarity, sensed by peripheral osmoreceptors, triggers sympatho-excitation likely arising from a spinal mechanism. Osmosensory transduction involves transient receptor potential vanilloid 4 channels (TRPV4) expressed on afferent neurons with their cell bodies in the dorsal root ganglia (delta;RG). Patients with familial dysautonomia (FD, hereditary sensory and autonomic neuropathy type-III) have a reduced number of afferent neurons in the DRG. The aim of our study was to investigate whether a pronounced osmopressor responsewas also present in patientswith FD. Nine patients withFDand 6with chronic autonomic failure participated in this study (5 with MSA and 1 with PAF). Beat-to-beat BP was recorded in a supine position before and following the ingestion of 500 ml of room temperature water for 30 min. As expected, in patients with autonomic failure, mean blood pressure (MBP) increased significantly after water ingestion (from 104 +/- 13 to 128 +/- 20 mmHg, p<0.05, max response 19 +/- 9 mmHg, p<0.01). In contrast, in patients with FD, water ingestion did not increase MBP significantly over the 30 min period (90 +/- 13 to 94 +/- 13 mmHg, NS, max response 7 +/- 11 mmHg, NS,). Thus, the response to water drinking differed significantly between the two groups (2-way ANOVA: p<0.0001). These findings suggest an absence of functional peripheral osmoreceptors in FD patients and may have therapeutic implications

Hippocampal population codes play an important role in representation of spatial environment and spatial navigation. Uncovering the internal representation of hippocampal population codes will help understand neural mechanisms of the hippocampus. For instance, uncovering the patterns represented by rat hippocampus (CA1) pyramidal cells during periods of either navigation or sleep has been an active research topic over the past decades. However, previous approaches to analyze or decode firing patterns of population neurons all assume the knowledge of the place fields, which are estimated from training data a priori. The question still remains unclear how can we extract information from population neuronal responses either without a priori knowledge or in the presence of finite sampling constraint. Finding the answer to this question would leverage our ability to examine the population neuronal codes under different experimental conditions. Using rat hippocampus as a model system, we attempt to uncover the hidden "spatial topology" represented by the hippocampal population codes. We develop a hidden Markov model (HMM) and a variational Bayesian (VB) inference algorithm to achieve this computational goal, and we apply the analysis to extensive simulation and experimental data. Our empirical results show promising direction for discovering structural patterns of ensemble spike activity during periods of active navigation. This study would also provide useful insights for future exploratory data analysis of population neuronal codes during periods of sleep.