Neuroanatomical Relationships between Orexin/Hypocretin-Containing Neurons/Nerve Fibers and Nicotine-Induced c-Fos-Activated Cells of the Reward-Addiction Neurocircuitry.

Orexin/hypocretin-containing neurons in lateral hypothalamus (LH) are implicated in the neurobiology of nicotine addiction. However, the neuroanatomical relationships between orexin-neurons/nerve fibers and nicotine-activated cells within the reward-addiction neurocircuitry is not known. In the present study in mice, we first used c-Fos immunohistochemistry to identify CNS cells stimulated by an acute single injection of nicotine (NIC, 2 mg/kg, IP). Sequential double-labelling was then performed to identify the location of orexin-containing neurons and nerve fibers with respect to NIC-induced c-Fos activated cells and/or tyrosine hydroxylase (TH) immunoreactive (IR) cells of the mesocorticolimbic reward-addiction pathways. Orexin-IR nerve fibers and terminals were detected at multiple sites of the NIC reward-addiction circuitry in close apposition to, and intermingled with, NIC-induced c-Fos-IR cells of locus coeruleus (LC), ventral tegmental area (VTA), nucleus accumbens (Acb), LH and paraventricular thalamic nucleus (PVT). Double-labelling of orexin with TH showed frequent contact between orexin-IR nerve fibers and noradrenergic cells of LC. However, there was infrequent contact between the orexinergic fibers and the TH-expressing dopaminergic cells of VTA, dorsal raphe nucleus (DR), posterior hypothalamus (DA11), arcuate hypothalamic nucleus (DA12) and periventricular areas (DA14). The close anatomical contact between orexinergic nerve fibers and NIC-activated cells at multiple sites of the reward-addiction pathways suggests that orexinergic projections from LH are likely to be involved in modulating activity of the neurons that are directly impacted by acute administration of nicotine.

The Sensory Impact of Nicotine on Noradrenergic and Dopaminergic Neurons of the Nicotine Reward - Addiction Neurocircuitry.

The sensory experience of smoking is a key component of nicotine addiction known to result, in part, from stimulation of nicotinic acetylcholine receptors (nAChRs) at peripheral sensory nerve endings. Such stimulation of nAChRs is followed by activation of neurons at multiple sites in the mesocorticolimbic reward pathways. However, the neurochemical profiles of CNS cells that mediate the peripheral sensory impact of nicotine remain unknown. In the present study in mice, we first used c-Fos immunohistochemistry to identify CNS cells stimulated by nicotine (NIC, 40 µg/kg, IP) and by a peripherally-acting analog of nicotine, nicotine pyrrolidine methiodide (NIC-PM, 30 µg/kg, IP). Sequential double-labelling was then performed to determine whether noradrenergic and dopaminergic neurons of the nicotine reward-addiction circuitry were primary targets of NIC and NIC-PM. Double-labelling of NIC and/or NIC-PM activated c-Fos immunoreactive cells with tyrosine hydroxylase (TH) showed no apparent c-Fos expression by the dopaminergic cells of the ventral tegmental area (VTA). With the exception of sparse numbers of TH immunoreactive D11 cells, dopamine-containing neurons in other areas of the reward-addiction circuitry, namely periaqueductal gray, and dorsal raphe, were also devoid of c-Fos immunoreactivity. Noradrenergic neurons of locus coeruleus (LC), known to innervate VTA, were activated by both NIC and NIC-PM. These results demonstrate that noradrenergic neurons of LC are among the first structures that are stimulated by single acute IP injection of NIC and NIC-PM. Dopaminergic neurons of VTA and other CNS sites, did not respond to acute IP administration of NIC or NIC-PM by induction of c-Fos.

Artery of Percheron Infarction as an Unusual Cause of Korsakoff's Syndrome.

The Korsakoff syndrome is defined as "an abnormal mental state in which memory and learning are affected out of all proportion to other cognitive functions in an otherwise alert and responsive patient." Confabulation refers to false or erroneous memories arising, not deliberately, in the context of a neurological amnesia and is often thought of as pathognomonic of the Korsakoff syndrome. Although the exact pathophysiology is unknown, various studies have identified brain lesions in the thalami, mammillary bodies, and frontal cortex. We report a case of a 68-year-old male presenting with acute altered mental status on July 16, 2015. The neuropsychological dysfunctions included prominent Korsakoff's syndrome, which became apparent when the altered mental status resolved. Amnesia was accompanied by prominent confabulation, disorientation, and lack of insight into his own disability. Neuroradiological data indicated that the intralaminar and dorsomedial nuclei in bilateral thalami were infarcted by occlusion of the artery of Percheron. We believe that ours is one of few reported cases of Korsakoff syndrome in a patient with infarction involving the territory of the artery of Percheron. We conclude that bilateral thalamic lesions could cause Korsakoff's syndrome and the intralaminar and dorsomedial nuclei might be important structures in the pathogenesis of confabulation.

High rate of microbleed formation following primary intracerebral hemorrhage.

BACKGROUND: We sought to investigate the frequency of microbleed development following intracerebral hemorrhage in a predominantly African-American population and to identify predictors of new microbleed formation. AIMS AND/OR HYPOTHESIS: To investigate the frequency and predictors of new microbleeds following intracerebral hemorrhage. METHODS: The DECIPHER study was a prospective, longitudinal, magnetic resonance-based cohort study designed to evaluate racial/ethnic differences in risk factors for microbleeds and to evaluate the prognostic impact of microbleeds in this intracerebral hemorrhage population. We evaluated new microbleed formation in two time periods: from baseline to 30 days and from 30 days to year 1. RESULTS: Of 200 subjects enrolled in DECIPHER, 84 had magnetic resonance imaging at all required time points to meet criteria for this analysis. In the baseline to day 30 analysis, 11 (13·1%) had new microbleeds, compared with 25 (29·8%) in the day 30 to year 1 analysis. Logistic regression analysis demonstrated that baseline number of microbleeds [odds ratio 1·05 (95% confidence interval 1·01, 1·08), P = 0·01] was associated with new microbleed formation at 30 days. A logistic regression model predicting new microbleed at one-year included baseline number of microbleeds [odds ratio 1·05 (1·00, 1·11), P = 0·046], baseline age [odds ratio 1·05 (1·00, 1·10), P = 0·04], and white matter disease score [odds ratio 1·18 (0·96, 1·45). P = 0·115]. Overall, 28 of 84 (33·3%) intracerebral hemorrhage subjects formed new microbleeds at some point in the first year post-intracerebral hemorrhage. CONCLUSIONS: We found that one-third of intracerebral hemorrhage subjects in this cohort surviving one-year developed new microbleeds, which suggests a dynamic and rapidly progressive vasculopathy. Future studies are needed to examine the impact of new microbleed formation on patient outcomes.

Neuroanatomical circuitry mediating the sensory impact of nicotine in the central nervous system.

Direct actions of nicotine in the CNS appear to be essential for its reinforcing properties. However, activation of nicotinic acetylcholine receptors (nAChRs) on afferent sensory nerve fibers is an important component of addiction to, and withdrawal from, cigarette smoking. The aim of the present study was to identify the neuroanatomical substrates activated by the peripheral actions of nicotine and to determine whether these sites overlap brain structures stimulated by direct actions of nicotine. Mouse brains were examined by immunohistochemistry for c-Fos protein after intraperitoneal injection of either nicotine hydrogen tartrate salt (NIC; 30 and 40 µg/kg) or nicotine pyrrolidine methiodide (NIC-PM; 20 and 30 µg/kg). NIC-PM induced c-Fos immunoreactivity (IR) at multiple brain sites. In the brainstem, c-Fos IR was detected in the locus coeruleus, laterodorsal tegmental nucleus, and pedunculotegmental nucleus. In the midbrain, c-Fos IR was observed in areas overlapping the ventral tegmental area (VTA), which includes the paranigral nucleus, parainterfascicular nucleus, parabrachial pigmental area, and rostral VTA. Other structures of the nicotine brain-reward circuitry activated by NIC-PM included the hypothalamus, paraventricular thalamic nucleus, lateral habenular nucleus, hippocampus, amygdala, accumbens nucleus, piriform cortex, angular insular cortex, anterior olfactory nucleus, lateral septal nucleus, bed nucleus of stria terminalis, cingulate and medial prefrontal cortex, olfactory tubercle, and medial and lateral orbital cortex. NIC, acting through central and peripheral nAChRs, produced c-Fos IR in areas that overlapped NIC-PM-induced c-Fos-expressing sites. These neuroanatomical data are the first to demonstrate that the CNS structures that are the direct targets of nicotine are also anatomical substrates for the peripheral sensory impact of nicotine.

Unique presentation of akinetic mutism and coexisting thyroid storm relating to stroke.

Akinetic mutism is described in various clinical presentations but typically is defined as a state wherein the patient appears awake but does not move or speak. It can be divided into two different subtypes; the most common subtypes depend on the lesion location, mesencephalic-diencephalic region, also called apathetic akinetic mutism (somnolent mutism), and those involving the anterior cingulate gyrus and adjacent frontal lobes called hyperpathic akinetic mutism. The pathway of akinetic mutism is believed to originate from circuits that link the frontal and subcortical structures. This case reports a 48-year-old African American female with bilateral anterior cerebral artery stroke and akinetic mutism with coexisting thyroid storm. This patient with bilateral anterior cerebral artery infarcts presented with characteristics that are typical for akinetic mutism such as having intact eye movements but an inability to respond to auditory or visual commands. With the incidence of bilateral anterior cerebral artery (ACA) ischemic stroke being rare and the incidence of akinetic mutism secondary to ischemic stroke even rarer, we suspect that this patient potentially had a unilateral occlusion of anomalous anterior cerebral vasculature.

A rare sequela of acute disseminated encephalomyelitis.

Acute disseminated encephalomyelitis is a demyelinating disease, typically occurring in children following a febrile infection or a vaccination. Primary and secondary immune responses contribute to inflammation and subsequent demyelination, but the exact pathogenesis is still unknown. Diagnosis of acute disseminated encephalomyelitis is strongly suggested by temporal relationship between an infection or an immunization and the onset of neurological symptoms. Biopsy is definitive. In general, the disease is self-limiting and the prognostic outcome is favorable with anti-inflammatory and immunosuppressive agents. Locked-in syndrome describes patients who are awake and conscious but have no means of producing limb, speech, or facial movements. Locked-in syndrome is a rare complication of acute disseminated encephalomyelitis. We present a case of incomplete locked-in syndrome occurring in a 34-year-old male secondary to acute disseminated encephalomyelitis. Our case is unique, as acute disseminated encephalomyelitis occurred in a 34-year-old which was poorly responsive to immunosuppression resulting in severe disability.

Prevalence and clinical correlation of left ventricular systolic dysfunction in african americans with ischemic stroke.

BACKGROUND: The goal of the present study was to determine the prevalence of left ventricular systolic dysfunction (LVSD) and associated clinical correlates in African Americans (AA) diagnosed with ischemic stroke (IS). METHODS: Retrospective chart analysis was done on all diagnosed AA IS patients between January 2010 and March 2012. Patients with atrial fibrillation were excluded. A total of 147 patients were included in the study. Transthoracic 2-dimensional echocardiography was used to assess left ventricular systolic function, and study groups were categorized as normal, mild, moderate, and severely abnormal, based on the ejection fraction (EF). Available imaging studies were analyzed for data collection. Logistic regression and Pearson chi-square tests were performed. RESULTS: Normal EF was present in 114 of 147 patients (78%). Mild abnormality was present in 9 of 147 (6%), moderate in 8 of 147 (5%), and severe in 16 of 147 (11%) patients. In patients with mildly reduced EF, smoking was the most common (RF). In patients with moderately and severely reduced EFs, hypertension was the most common RF. History of smoking was commonly found in systolic dysfunction group compared with normal group (P = .001). Logistic regression analysis revealed that smoking and advanced age were the significant predictors for LVSD. Large-vessel IS were more common in systolic dysfunction group than normal EF group (P = .017). CONCLUSIONS: Prevalence of LVSD in AA with IS was 22% in our study. Smoking was a significant modifiable RF associated with systolic dysfunction. A history of smoking and higher age could predict the occurrence of LVSD. There were more large-vessel IS in patients with LVSD.

A Rare Case of Immune Reconstitution Inflammatory Syndrome Development in an Immunocompromised Patient with Progressive Multifocal Leukoencephalopathy and Multicentric Castleman's Disease.

Immune reconstitution inflammatory syndrome (IRIS) development in HIV with preexistent progressive multifocal leukoencephalopathy (PML) has been extensively studied. PML-IRIS typically manifests clinically as new or worsening neurologic symptoms in conjunction with enlarging CNS lesions and occurs in approximately 10-20 percent of HIV-infected patients with PML who begin HAART. Likewise, Multicentric Castleman's Disease (MCD), a rare malignant lymphoproliferative disorder, has a strong and well-known association with HIV. Our case provides a rare instance of PML-IRIS in combination with MCD in an HIV-positive individual. The combination of all three diseases has never been reported in the literature. Both MCD and PML were present during initial determination of HIV infection in our patient and their disease courses were altered during the subsequent development of IRIS.

Association of chronic kidney disease with cerebral microbleeds in patients with primary intracerebral hemorrhage.

BACKGROUND AND PURPOSE: To investigate the relationship between chronic kidney disease (CKD) and MRI-defined cerebral microbleeds (CMB), a harbinger of future intracerebral hemorrhage (ICH), among patients with a recent history of primary ICH. METHODS: Using data from a predominantly black cohort of patients with a recent ICH-enrolled in an observational study between September 2007 and June 2011, we evaluated the association between CKD (defined as estimated low glomerular filtration rate<60 mL/min per 1.73 m(2)) and CMB on gradient-echo MRI. Multivariable models were generated to determine the contribution of CKD to the presence, number, and location of CMB. RESULTS: Of 197 subjects with imaging data, mean age was 59 years, 48% were women, 73% were black, 114 (58%) had ≥1 CMBs, and 52 (26%) had CKD. Overall, CKD was associated with presence of CMB (adjusted odds ratio, 2.70; 95% confidence interval [CI], 1.10-6.59) and number of CMB (adjusted relative risk, 2.04; 95% CI, 1.27-3.27). CKD was associated with CMB presence (adjusted odds ratio, 3.44; 95% CI, 1.64-7.24) and number (adjusted relative risk, 2.46; 95% CI, 1.11-5.42) in black patients, but not CMB presence (adjusted odds ratio, 3.00; 95% CI, 0.61-14.86) or number (adjusted relative risk, 1.03; 95% CI: 0.22-4.89) in non-Hispanic white patients (interactions by race were statistically not significant). CONCLUSIONS: CKD is associated with a greater presence and number of CMB in ICH patients, particularly in patients of black race. Future studies should assess whether low estimated glomerular filtration rate may be a CMB risk marker or potential therapeutic target for mitigating the development of CMB.

Posterior Reversible Encephalopathy Syndrome in a Patient with Newly Diagnosed HIV Infection and End Stage Renal Disease.

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome in which patients present with an acute or subacute clinical presentation of seizures, visual disturbances, headache, and altered mental status. The pathophysiology of PRES may be explained by endothelial dysfunction that leads to transudation of fluids and protein, resulting in vasogenic cerebral edema. PRES is typically associated with many conditions such as hypertension, uremia, immunosuppressive drugs, and sepsis. This is a case report of a 39-year-old woman with untreated HIV infection and end-stage renal disease (ESRD) who developed PRES with a normal blood pressure and no other known causes of PRES. Untreated HIV is associated with known endothelial dysfunction and we believe that this, in combination with her untreated end-stage renal disease, contributed to her unique presentation of PRES. Although uncommon in HIV-infected patients and challenging to diagnose, prompt recognition of PRES is critical to provide appropriate care and ensure reversibility of the vasogenic edema seen in PRES.

Myasthenia gravis: a review.

Acquired myasthenia gravis is a relatively uncommon disorder, with prevalence rates that have increased to about 20 per 100,000 in the US population. This autoimmune disease is characterized by muscle weakness that fluctuates, worsening with exertion, and improving with rest. In about two-thirds of the patients, the involvement of extrinsic ocular muscle presents as the initial symptom, usually progressing to involve other bulbar muscles and limb musculature, resulting in generalized myasthenia gravis. Although the cause of the disorder is unknown, the role of circulating antibodies directed against the nicotinic acetylcholine receptor in its pathogenesis is well established. As this disorder is highly treatable, prompt recognition is crucial. During the past decade, significant progress has been made in our understanding of the disease, leading to new treatment modalities and a significant reduction in morbidity and mortality.

Acute ischemic stroke secondary to iron deficiency anemia: a case report.

A rare case of acute ischemic stroke in a young patient with iron deficiency anemia (IDA) is reported. IDA has been suggested to have an association with stroke, but few cases have proven it thus far. Three physiological mechanisms explaining IDA to ischemic stroke include a hypercoagulable state secondary to IDA, thrombocytosis secondary to IDA, and anemic hypoxia induced by IDA. Our paper shows an example of a hypoxia-induced stroke secondary to IDA in a young woman with menorrhagia. Thrombus formation was ruled out as the Magnetic Resonance Angiogram (MRA) showed no evidence. As all other known causes for stroke were ruled out, the patient's IDA is a reasonable cause for her stroke. Iron deficiency decreases the amount of hemoglobin, which consequently decreases the amount of oxygen in the blood resulting in low-oxygen delivery to the brain. This causes hypoxic conditions in the brain, leading to death of brain tissue. Thus, we suggest a possible relationship between IDA and ischemic stroke in young adults. Considering IDA as one of the risk factors for ischemic stroke and treating with timely transfusions would be an important step one can take to prevent stroke.

Neuronal expression of bitter taste receptors and downstream signaling molecules in the rat brainstem.

Previous studies have shown that molecules of the taste transduction pathway may serve as biochemical markers for chemoreceptive cells in respiratory and gastrointestinal tracts. In this study, we tested the hypothesis that brainstem neurons contain signaling molecules similar to those in taste buds which may sense the chemical composition of brain extracellular fluids. We used the reverse transcription polymerase chain reaction (RT-PCR), Western blot and immunohistochemical techniques to evaluate presence of different bitter-responsive type 2 taste receptors (T2Rs), their associated G-protein α-gustducin, the downstream signaling molecules phospholipase C isoform ß2 (PLC-ß2) and transient receptor potential melastatin 5 (TRPM5) in the brainstem of rats. RT-PCR confirmed the mRNA coding for α-gustducin, PLC-ß2, TRPM5 and rT2R1 but not that of rT2R16, rT2R26 and rT2R38 in the medulla oblongata. Western blotting confirmed the presence of α-gustducin at the protein level in rat brainstem. Immunohistochemistry identified cells expressing α-gustducin and PLC-ß2 at multiple cardiorespiratory and CO(2)/H(+) chemosensory sites, including rostral ventral medulla, facial, parapyramidal, solitary tract, hypoglossal and raphe nuclei. In the medullary raphe, α-gustducin and PLC-ß2 were colocalized with a subpopulation of tryptophan hydroxylase (TPH)-immunoreactive serotonergic neurons, a subset of which has respiratory CO(2)/H(+) chemosensitivity. Presence of the T2R1 gene and other genes and proteins of the bitter taste transduction pathway in the brainstem implies additional functions for taste receptors and their effector molecules apart from their gustatory function.

Neuroanatomical evidence for a putative autocrine/paracrine signaling system involving nicotinic acetylcholine receptors, purinergic receptors, and nitric oxide synthase in the airways.

Nicotine in tobacco smoke is thought to stimulate sensory nerve fibers by receptors that are located on airway epithelial cells and on terminal branches of C-fiber afferents, but the exact neurochemical substrate that mediates the sensory effects of nicotine associated with cigarette smoking is not clear. ATP and nitric oxide (NO) have both been implicated in lung responsiveness to airborne chemicals such as nicotine. However, the neuroanatomical and functional relationships between nicotinic acetylcholine receptors (nAChRs), purinergic signaling, and NO are not known, and the main source of NO in the airways is not clear. In the present study, we performed RT-PCR to confirm the presence of mRNA for all three isoforms of nitric oxide synthase (NOS), neuronal (n-NOS), endothelial (e-NOS), and inducible (i-NOS), in the lung. Sequential double labeling was performed to assess the site of expression of the different NOS isoforms with respect to nAChRs and purinergic receptors (P2X3R) of the intrapulmonary airways. RT-PCR confirmed the presence of n-NOS, e-NOS, and i-NOS in the lung, and immunohistochemical studies verified their expression by epithelial cells at all levels of the intrapulmonary airways, including the terminal and respiratory bronchioles. Sequential double labeling demonstrated coexpression of n-NOS and/or i-NOS with nAChR- and P2X3R-expressing cells. These neuroanatomical findings suggest that bronchial epithelial cells may be a primary source of NO in the intrapulmonary airways and that the production and release of NO may be regulated by an autocrine/paracrine signaling system involving nAChRs and P2X3Rs.

Predictors of highly prevalent brain ischemia in intracerebral hemorrhage.

OBJECTIVE: This study was undertaken to determine the prevalence, characteristics, risk factors, and temporal profile of concurrent ischemic lesions in patients with acute primary intracerebral hemorrhage (ICH). METHODS: Patients were recruited within a prospective, longitudinal, magnetic resonance imaging (MRI)-based study of primary ICH. Clinical, demographic, and MRI data were collected on all subjects at baseline and 1 month. RESULTS: Of the 138 patients enrolled, mean age was 59 years, 54% were male, 73% were black, and 84% had a history of hypertension. At baseline, ischemic lesions on diffusion-weighted imaging (DWI) were found in 35% of patients. At 1 month, lesions were present in 27%, and of these lesions, 83% were new and not present at baseline. ICH volume (p = 0.025), intraventricular hemorrhage (p = 0.019), presence of microbleeds (p = 0.024), and large, early reductions in mean arterial pressure (p = 0.003) were independent predictors of baseline DWI lesions. A multivariate logistical model predicting the presence of 1-month DWI lesions included history of any prior stroke (p = 0.012), presence of 1 or more microbleeds (p = 0.04), black race (p = 0.641), and presence of a DWI lesion at baseline (p = 0.007). INTERPRETATION: This study demonstrates that >⅓ of patients with primary ICH have active cerebral ischemia at baseline remote from the index hematoma, and » of patients experience ongoing, acute ischemic events at 1 month. Multivariate analyses implicate blood pressure reductions in the setting of an active vasculopathy as a potential underlying mechanism. Further studies are needed to determine the impact of these lesions on outcome and optimal management strategies to arrest vascular damage.

Preventing recurrence of thromboembolic events through coordinated treatment in the District of Columbia.

RATIONALE: PROTECT DC examines whether stroke navigators can improve cardiovascular risk factors in urban underserved individuals newly hospitalized for stroke or ischemic attack. Within one-year of hospital discharge, up to one-third of patients no longer adhere to secondary prevention behaviors. Adherence rates are lower in minority-underserved groups, contributing to health disparities. In-hospital programs increase use of stroke prevention therapies but may not be as successful in underserved individuals. In these groups, low literacy, limited healthcare access, and sparse community resources may reduce adherence. Lay community health workers (navigators) improve adherence in other illnesses through education and assisting in overcoming barriers to achieving desired health behaviors and obtaining needed healthcare services. AIMS AND DESIGN: PROTECT DC is a Phase II, single-blind, randomized, controlled trial comparing in-hospital education plus stroke navigators to usual care. Atherogenic ischemic stroke and transient ischemic attack survivors are recruited from Washington, DC hospitals. Navigators meet with participants during the index hospitalization, perform home visits, and meet by phone. They focus on stroke education, medication compliance, and overcoming practical barriers to adherence. The interventions are driven by the theories of reasoned action and planned behavior. STUDY OUTCOMES: The primary dependent measure is a summary score of four objective measures of stroke risk factor control: systolic blood pressure, low-density lipoprotein, hemoglobin Hb A1C, and antiplatelet agent pill counts. Secondary outcomes include stroke knowledge, exercise, dietary modification, and smoking cessation. CONCLUSION: PROTECT DC will determine whether a Phase III trial of stroke navigation for urban underserved individuals to improve adherence to secondary stroke prevention behaviors is warranted.

Racial disparities in tissue plasminogen activator treatment rate for stroke: a population-based study.

BACKGROUND AND PURPOSE: Some prior studies have shown that racial disparities exist in intravenous tissue plasminogen activator (tPA) use for acute ischemic stroke. We sought to determine whether race was associated with tPA treatment for stroke in a predominantly black urban population. METHODS: Systematic chart abstraction was performed on consecutive hospitalized patients with ischemic stroke from all 7 acute care hospitals in the District of Columbia from February 1, 2008, to January 31, 2009. RESULTS: Of 1044 patients with ischemic stroke, 74% were black, 19% non-Hispanic white, and 5% received intravenous tPA. Blacks were one third less likely than whites to receive intravenous tPA (3% versus 10%, P<0.001). However, blacks were also less likely than whites to present within 3 hours of symptom onset (13% versus 21%, P=0.004) and also less likely to be tPA-eligible (5% versus 13%, P<0.001). Of those who presented within 3 hours, blacks were almost half as likely to be treated with intravenous tPA than whites (27% versus 46%, P=0.023). The treatment rate for tPA-eligible patients was similar for blacks and whites (70% versus 76%, P=0.62). CONCLUSIONS: In this predominantly black urban population hospitalized for acute ischemic stroke, blacks were significantly less likely to be treated with intravenous tPA due to contraindications to treatment, delayed presentation, and stroke severity. Effective interventions designed to increase treatment in this population need to focus on culturally relevant education programs designed to address barriers specific to this population.

Association of physical activity level and stroke outcomes in men and women: a meta-analysis.

OBJECTIVE: The protective effect of physical activity (PA) on risk of stroke remains controversial as a result of lack of insight into the sources of heterogeneity between studies. We performed a comprehensive meta-analysis of studies to (1) quantify the association between PA level and risk of stroke outcomes and (2) test the hypothesis that the association of PA level with stroke outcomes will be similar between men and women. The outcome measures are stroke incidence, stroke mortality, or both. METHODS: Cohort studies were identified by searching MEDLINE and EMBASE (from 1986 to 2005) and meta-analysis conducted according to meta-analysis of Observational Studies in Epidemiology (MOOSE) group recommendations. Data were reported as pooled relative risk (RR) and 95% confidence intervals (CI) using random-effects models to assess the association of stroke outcomes with PA level. Heterogeneity was investigated, and sensitivity analysis was performed. Stratified analysis by gender was performed. RESULTS: Of 992 articles, 13 satisfied all eligibility criteria and were studied. Compared with low PA, moderate PA caused an 11% reduction in risk of stroke outcome (RR = 0.89, 95% CI 0.86-0.93, p < 0.01) and high PA a 19% reduction (RR = 0.81, CI 0.77-0.84, p < 0.01). Among the men, results showed a 12% reduction in risk associated with moderate PA (RR = 0.88, CI 0.82-0.94, p < 0.01) and 19% reduction for high PA (RR = 0.81, CI 0.75-0.87, p < 0.01). Among the women, results showed a 24% reduction in risk for high PA (RR = 0.76, CI 0.64-.89, p < 0.01). There was, however, no significant risk reduction associated with a moderate PA level in women. CONCLUSIONS: Increased PA level appears beneficial in reduction of risk of stroke and related outcomes. However, higher levels of PA may be required in women to achieve as significant a risk reduction as in men. An exercise regimen tailored to women to improve related physiological mechanisms will likely be beneficial.

Co-expression of nAChRs and molecules of the bitter taste transduction pathway by epithelial cells of intrapulmonary airways.

AIMS: The ability to sense the bitter taste of nicotine is an important component of addiction to, and withdrawal from, cigarette smoking. alpha-Gustducin and phospholipase C-beta2 (PLC-beta2), molecules involved in the taste transduction pathway, have been identified in airway epithelial solitary chemosensory cells (SCCs). Airway epithelial cells also express multiple nicotinic acetylcholine receptors (nAChRs). However, the relationship between nAChRs and molecules of taste transduction in response to nicotine is not known. This study was designed to determine whether nAChRs and the taste transduction molecules alpha-gustducin, PLC-beta2 and bitter taste receptors (T2R38) reside at sites of the intrapulmonary airways where interaction with the nicotine components of cigarette smoke is likely. MAIN METHODS: We used the reverse transcription-polymerase chain reaction (RT-PCR) to detect alpha-gustducin, PLC-beta2 and T2R38 mRNA and immunohistochemistry to localize expression of these proteins by nAChR expressing cells of the airway. KEY FINDINGS: RT-PCR demonstrated the presence of mRNA for alpha-gustducin, PLC-beta2 and T2R38. Immunohistochemistry showed the expression of alpha-gustducin, PLC-beta2 and T2R38 by subsets of epithelial cells at all levels of the intrapulmonary airways including bronchi, terminal and respiratory bronchioles. Double labeling demonstrated the co-expression of alpha-gustducin with alpha3, alpha4, alpha5, alpha7 and beta2, as well as, PLC-beta2 and T2R38 with alpha4, alpha5 and beta2 nAChR subunits. SIGNIFICANCE: These findings provide morphological evidence for the presence of molecules of the bitter taste transduction pathway in nAChR expressing SCCs of the intrapulmonary airways. These SCCs may, thus, constitute a peripheral component of the bitter taste signal transduction pathway for nicotine.