Is contralateral neck treatment necessary in early carcinoma of the tonsil?

One of the most distressing complications of radiation therapy of the head and neck cancers is xerostomia. Treatment of both parotid glands to high doses would be expected to result in high probability of symptomatic xerostomia. Treatment of early carcinomas of the tonsil with techniques to include bilateral upper neck nodes would result in xerostomia whereas treatment limited to the primary and ipsilateral neck only would avoid it. The latter technique has been used in 32 patients with carcinoma of the tonsil treated in Rush-Presbyterian-St. Luke's Medical Center from 1965 through 1975. Of 20 patients with No or N1 disease treated this way, there were no contralateral neck recurrences with controlled primary and ipsilateral neck.     

Epidural Hematoma Producing Brown-Sequard Syndrome: A Case Due to Ruptured Hemangioma with Magnetic Resonance Imaging Findings

A man developed spontaneous spinal epidural hematoma secondary to ruptured hemangioma with a clinical picture resembling acute partial Brown-Sequard syndrome. Diagnosis by magnetic resonance imaging (MRI) allowed prompt surgical decompression and complete reversal of the neurological deficits. The diagnosis, etiology, and MRI findings of spinal epidural hematomas are discussed.     

From the Cover: Science for managing ecosystem services: Beyond the Millennium Ecosystem Assessment

The Millennium Ecosystem Assessment (MA) introduced a new framework for analyzing social–ecological systems that has had wide influence in the policy and scientific communities. Studies after the MA are taking up new challenges in the basic science needed to assess, project, and manage flows of ecosystem services and effects on human well-being. Yet, our ability to draw general conclusions remains limited by focus on discipline-bound sectors of the full social–ecological system. At the same time, some polices and practices intended to improve ecosystem services and human well-being are based on untested assumptions and sparse information. The people who are affected and those who provide resources are increasingly asking for evidence that interventions improve ecosystem services and human well-being. New research is needed that considers the full ensemble of processes and feedbacks, for a range of biophysical and social systems, to better understand and manage the dynamics of the relationship between humans and the ecosystems on which they rely. Such research will expand the capacity to address fundamental questions about complex social–ecological systems while evaluating assumptions of policies and practices intended to advance human well-being through improved ecosystem services.     

National Heart, Lung, and Blood Institute guidelines and asthma management practices among inner-city pediatric primary care providers

BACKGROUND AND OBJECTIVE: Most surveys of pediatric outpatient asthma management obtain information from parents and caregivers. Studies based on surveys of primary health-care providers are sparse. Suboptimal outpatient management may play a role in the high hospitalization rates among inner-city asthmatic children. Asthma management practices were compared between hospital-based and community-based primary care providers (PCPs). Adherence to National Heart, Lung, and Blood Institute (NHLBI) guidelines was evaluated, along with practices not clearly defined in the guidelines such as use of oral cough medicines and albuterol suspension. DESIGN/METHODS: An 8-point questionnaire was administered to 48 community-based and 32 hospital-based PCPs practicing in inner-city neighborhoods. The questionnaire addressed three "positive" practices (classification of asthma severity, use of asthma action plan, and use of a spacer) and three "negative" practices (use of cough syrup, use of albuterol suspension, and preferential use of leukotriene modifiers instead of inhaled corticosteroids as the first line of preventive therapy). Response options were as follows: never, rarely, sometimes, and always, scored from 0 to 3. The two physician groups were compared on score means for the positive and negative practices using a t test with statistical significance set at p < 0.05. RESULTS: Overall, the rate of adherence to the positive practices was high, with no significant difference between the two groups. Negative practices, while present in both the groups, were reported significantly more often by the community-based group, particularly the use of cough suppressants and albuterol suspension. CONCLUSIONS: Greater emphasis is needed to increase the awareness among PCPs of the NHLBI guideline recommendations, as suboptimal outpatient asthma management may contribute to the disproportionately higher hospitalization rates among inner-city asthmatic children. Clarification on the use of potentially harmful medications and those of doubtful value need to be incorporated in the guidelines. The extent to which these negative practices contribute to the elevated pediatric hospitalization rates warrants further investigation.     

Genetic modification of cerebral arterial wall: implications for prevention and treatment of cerebral vasospasm

Genetic modification of cerebral vessels represents a promising and novel approach for prevention and/or treatment of various cerebral vascular disorders, including cerebral vasospasm. In this review, we focus on the current understanding of the use of gene transfer to the cerebral arteries for prevention and/or treatment of cerebral vasospasm following subarachnoid hemorrhage (SAH). We also discuss the recent developments in vascular therapeutics, involving the autologous use of progenitor cells for repair of damaged vessels, as well as a cell-based gene delivery approach for the prevention and treatment of cerebral vasospasm.     

Racial Health Disparity and COVID-19

Journal of Neuroimmune Pharmacology - The infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and resultant coronavirus diseases-19 (COVID-19) disproportionally affects...     

1,3,8-Triazaspiro[4.5]decane-2,4-diones as efficacious pan-inhibitors of hypoxia-inducible factor prolyl hydroxylase 1-3 (HIF PHD1-3) for the treatment of anemia

The discovery of 1,3,8-triazaspiro[4.5]decane-2,4-diones (spirohydantoins) as a structural class of pan-inhibitors of the prolyl hydroxylase (PHD) family of enzymes for the treatment of anemia is described. The initial hit class, spirooxindoles, was identified through affinity selection mass spectrometry (AS-MS) and optimized for PHD2 inhibition and optimal PK/PD profile (short-acting PHDi inhibitors). 1,3,8-Triazaspiro[4.5]decane-2,4-diones (spirohydantoins) were optimized as an advanced lead class derived from the original spiroindole hit. A new set of general conditions for C-N coupling, developed using a high-throughput experimentation (HTE) technique, enabled a full SAR analysis of the spirohydantoins. This rapid and directed SAR exploration has resulted in the first reported examples of hydantoin derivatives with good PK in preclinical species. Potassium channel off-target activity (hERG) was successfully eliminated through the systematic introduction of acidic functionality to the molecular structure. Undesired upregulation of alanine aminotransferese (ALT) liver enzymes was mitigated and a robust on-/off-target margin was achieved. Spirohydantoins represent a class of highly efficacious, short-acting PHD1-3 inhibitors causing a robust erythropoietin (EPO) upregulation in vivo in multiple preclinical species. This profile deems spirohydantoins as attractive short-acting PHDi inhibitors with the potential for treatment of anemia.     

Current perspectives of the roles of the central norepinephrine system in anxiety and depression

Norepinephrine (NE) is a major monoamine neurotransmitter that has widespread effects across multiple brain areas to regulate arousal and stress responses. The underlying function of the NE cortical system is to balance vigilance/scanning behavior with focused attention on novel environmental stimuli and the state of arousal. The central NE system is involved intrinsically with the stress response system, and dysregulation within the NE system has been implicated in the pathogenesis of anxiety and depressive disorders. Central NE activity paradoxically has either anxiogenic or anxiolytic effects, depending on whether the time course of the stress is acute or chronic, whether the stress is predictable or unpredictable, and which underlying brain regions are affected. Under conditions of chronic stress, NE system activity dysregulation of the hypothalamic‐pituitary‐adrenal system may turn a homeostatic stress response into a pathological stress response. Data suggest that the NE interplay with the serotonin system may exert neurobiological normalization of the pathophysiological state of anxious depression. Accordingly, pharmacological interventions targeting the NE system can result in anxiolytic, rather than anxiogenic, outcomes when used to treat patients with anxiety and depression. Depression and Anxiety, 2010. © 2009 Wiley‐Liss, Inc.