Altered inflammasome activation in neonatal encephalopathy persists in childhood.

Neonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Inflammatory cytokines interleukin (IL)-1ß, IL-1ra and IL-18 are activated by the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat domain (LRR)- and NOD-like receptor protein 3 (NLRP3) inflammasome; furthermore, we aimed to examine the role of the inflammasome multiprotein complex involved in proinflammatory responses from the newborn period to childhood in NE. Cytokine concentrations were measured by multiplex enzyme-linked immunosorbent assay (ELISA) in neonates and children with NE in the absence or presence of lipopolysaccharide (LPS) endotoxin. We then investigated expression of the NLRP3 inflammasome genes, NLRP3, IL-1ß and ASC by polymerase chain reaction (PCR). Serum samples from 40 NE patients at days 1 and 3 of the first week of life and in 37 patients at age 4-7 years were analysed. An increase in serum IL-1ra and IL-18 in neonates with NE on days 1 and 3 was observed compared to neonatal controls. IL-1ra in NE was decreased to normal levels at school age, whereas serum IL-18 in NE was even higher at school age compared to school age controls and NE in the first week of life. Percentage of LPS response was higher in newborns compared to school-age NE. NLRP3 and IL-1ß gene expression were up-regulated in the presence of LPS in NE neonates and NLRP3 gene expression remained up-regulated at school age in NE patients compared to controls. Increased inflammasome activation in the first day of life in NE persists in childhood, and may increase the window for therapeutic intervention.

Advancing the Sustainability of US Agriculture through Long-Term Research.

Agriculture in the United States must respond to escalating demands for productivity and efficiency, as well as pressures to improve its stewardship of natural resources. Growing global population and changing diets, combined with a greater societal awareness of agriculture's role in delivering ecosystem services beyond food, feed, fiber, and energy production, require a comprehensive perspective on where and how US agriculture can be sustainably intensified, that is, made more productive without exacerbating local and off-site environmental concerns. The USDA's Long-Term Agroecosystem Research (LTAR) network is composed of 18 locations distributed across the contiguous United States working together to integrate national and local agricultural priorities and advance the sustainable intensification of US agriculture. We explore here the concept of sustainable intensification as a framework for defining strategies to enhance production, environmental, and rural prosperity outcomes from agricultural systems. We also elucidate the diversity of factors that have shaped the past and present conditions of cropland, rangeland, and pastureland agroecosystems represented by the LTAR network and identify priorities for research in the areas of production, resource conservation and environmental quality, and rural prosperity. Ultimately, integrated long-term research on sustainable intensification at the national scale is critical to developing practices and programs that can anticipate and address challenges before they become crises.

Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial.

We sought to determine whether high-dose folinic acid improves verbal communication in children with non-syndromic autism spectrum disorder (ASD) and language impairment in a double-blind placebo control setting. Forty-eight children (mean age 7 years 4 months; 82% male) with ASD and language impairment were randomized to receive 12 weeks of high-dose folinic acid (2 mg kg-1 per day, maximum 50 mg per day; n=23) or placebo (n=25). Children were subtyped by glutathione and folate receptor-α autoantibody (FRAA) status. Improvement in verbal communication, as measured by a ability-appropriate standardized instrument, was significantly greater in participants receiving folinic acid as compared with those receiving placebo, resulting in an effect of 5.7 (1.0,10.4) standardized points with a medium-to-large effect size (Cohen's d=0.70). FRAA status was predictive of response to treatment. For FRAA-positive participants, improvement in verbal communication was significantly greater in those receiving folinic acid as compared with those receiving placebo, resulting in an effect of 7.3 (1.4,13.2) standardized points with a large effect size (Cohen's d=0.91), indicating that folinic acid treatment may be more efficacious in children with ASD who are FRAA positive. Improvements in subscales of the Vineland Adaptive Behavior Scale, the Aberrant Behavior Checklist, the Autism Symptom Questionnaire and the Behavioral Assessment System for Children were significantly greater in the folinic acid group as compared with the placebo group. There was no significant difference in adverse effects between treatment groups. Thus, in this small trial of children with non-syndromic ASD and language impairment, treatment with high-dose folinic acid for 12 weeks resulted in improvement in verbal communication as compared with placebo, particularly in those participants who were positive for FRAAs.

Differential Cell Composition and Cytokine Expression Within Lymph Node Granulomas from BCG-Vaccinated and Non-vaccinated Cattle Experimentally Infected with Mycobacterium bovis.

Cattle vaccination against bovine tuberculosis (bTB) has been proposed as a supplementary method to help control the incidences of this disease. Bacillus Calmette-Guérin (BCG) is currently the only viable candidate vaccine for immunization of cattle against bTB, caused by Mycobacterium bovis (M. bovis). In an attempt to characterize the differences in the immune response following M. bovis infection between BCG-vaccinated and non-vaccinated animals, a combination of gross pathology, histopathology and immunohistochemical (IHC) analyses was used. BCG vaccination was found to significantly reduce the number of gross and microscopic lesions present within the lungs and lymph nodes. Additionally, the microscopically visible bacterial load of stages III and IV granulomas was reduced. IHC using cell surface markers revealed the number of CD68+ (macrophages), CD3+ (T lymphocytes) and WC1+ cells (γδ T cells) to be significantly reduced in lymph node granulomas of BCG-vaccinated animals, when compared to non-vaccinated animals. B lymphocytes (CD79a+) were significantly increased in BCG-vaccinated cattle for granulomas at stages II, III and IV. IHC staining for iNOS showed a higher expression in granulomas from BCG-vaccinated animals compared to non-vaccinated animals for all stages, being statistically significant in stages I and IV. TGFß expression decreased alongside the granuloma development in non-vaccinated animals, whereas BCG-vaccinated animals showed a slight increase alongside lesion progression. IHC analysis of the cytokines IFN-γ and TNF-α demonstrated significantly increased expression within the lymph node granulomas of BCG-vaccinated cattle. This is suggestive of a protective role for IFN-γ and TNF-α in response to M. bovis infection. Findings shown in this study suggest that the use of BCG vaccine can reduce the number and severity of lesions, induce a different phenotypic response and increase the local expression of key cytokines related to protection.

Síndrome «humpy-backed» en cerdos en España / «Humpy-backed» pigs’ syndrome in Spain

El síndrome «humpy-backed» fue descrito en cerdos por primera vez en el Reino Unido en 1984. El síndrome ha sido observado en algunos países pero la etiología y la patogenia son todavía desconocidas. Este caso describe la aparición de cerdos con «humpy-backed» en la lechonera de una granja de 3.800 cerdas situada en el noreste de España. El problema afectó aproximadamente al 3% de la progenie semanal de una línea genética particular de la granja compuesta por 450 cerdas. La incidencia alcanzó picos del 9-11% en algunas semanas. Los lechones aparecían deprimidos, con pelaje hirsuto y deterioro físico progresivo. En la necropsia, a pesar de la apariencia de lordosis, no se detectaron alteraciones en los huesos y articulaciones de la columna vertebral. Microscópicamente se observó periarteritis linfoplasmocítica en corazón, bazo, intestino, hígado, riñón, músculo esquelético, pulmón y meninges. También se observó miocarditis y miositis linfoplasmocítica con degeneración de fibras musculares esqueléticas. La apariencia macroscópica de lordosis se relacionó con infiltrado celular inflamatorio multiorgánico. Se asoció a un problema de tipo genético de los animales afectados, aunque podría haber una posible implicación de circovirus porcino tipo 2 (PCV2) y el virus del síndrome reproductivo y respiratorio porcino (PRRS) en la patogenia del síndrome, debido a la seropositividad frente a los mismos detectada en la granja (AU)

«Humpy-backed» pigs’ syndrome was firstly described in the United Kingdom in 1984. The syndrome has been reported in a few countries, but the ethiology and pathogenesis remains unclear. This report describes the appearance of «humpy-backed» piglets aetiology in the nursery of a 3800-sow farm in Northeast Spain. The problem affected around 3% of the weekly offspring from one particular genetic line present on the farm composed of 450 sows. The incidence reached peaks of 9-11% in some weeks. The piglets appeared depressed, with rough hair coat and progressive clinical deterioration. In the necropsy, despite the appearance of lordosis, no defect in the bones and joint of the vertebral spine were detected. Lympho-plasmacytic periarteritis was observed in heart, spleen, gut, liver, kidney, skeletal muscle, lung and meninges. Lympho-plasmacytic myocarditis and skeletal myositis with muscular fibre degeneration was also observed. The macroscopic appearance of lordosis was associated with a multiorganic inflammatory cell infiltration. There was an association with the genetic background of the affected animals although seropositivity to porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) was also found in the farm, pointing to a possible implication of viral infection in the pathogenesis of the syndrome (AU)

Ability of radial arterial palpation and observation of the pulse oximetry trace to estimate non-invasive systolic pressure in healthy volunteers and in women undergoing spinal anaesthesia for elective caesarean section.

We assessed the ability of palpating the radial arterial pulse and observing the oximeter trace to estimate the automated non-invasive systolic pressure reading in 20 healthy female volunteers and 20 parturients undergoing spinal anaesthesia for elective caesarean section. Using real-time values of cuff pressure during inflation/deflation, the pressure was recorded when the manually palpated radial arterial pulse or pulse oximeter waveform disappeared and reappeared. The actual measured systolic pressure was noted and the results compared using Bland-Altman analysis. In the volunteers, the bias/precision for radial arterial palpation was -12.9/22.1 mmHg (inflation) and -9.7/16.7 mmHg (deflation), and for oximetry 29.5/18.8 mmHg (inflation) and -20.7/21.7 mmHg (deflation). In the parturients, the bias/precision was -19.0/47.6 mmHg (inflation) and -15.5/51.0 mmHg (deflation) for arterial palpation, and 22.6/16.1 mmHg (inflation) and -14.2/19.9 mmHg (deflation) for oximetry. Our results suggest that neither method is accurate at estimating the non-invasive systolic pressure, with all except oximetry (inflation) underestimating it by approximately 10-20 mmHg and with poor precision.

Variable rainfall intensity and tillage effects on runoff, sediment, and carbon losses from a loamy sand under simulated rainfall.

The low-carbon, intensively cropped Coastal Plain soils of Georgia are susceptible to runoff, soil loss, and drought. Reduced tillage systems offer the best management tool for sustained row crop production. Understanding runoff, sediment, and chemical losses from conventional and reduced tillage systems is expected to improve if the effect of a variable rainfall intensity storm was quantified. Our objective was to quantify and compare effects of a constant (Ic) intensity pattern and a more realistic, observed, variable (Iv) rainfall intensity pattern on runoff (R), sediment (E), and carbon losses (C) from a Tifton loamy sand cropped to conventional-till (CT) and strip-till (ST) cotton (Gossypium hirsutum L.). Four treatments were evaluated: CT-Ic, CT-Iv, ST-Ic, and ST-Iv, each replicated three times. Field plots (n=12), each 2 by 3 m, were established on each treatment. Each 6-m2 field plot received simulated rainfall at a constant (57 mm h(-1)) or variable rainfall intensity pattern for 70 min (12-run ave.=1402 mL; CV=3%). The Iv pattern represented the most frequent occurring intensity pattern for spring storms in the region. Compared with CT, ST decreased R by 2.5-fold, E by 3.5-fold, and C by 7-fold. Maximum runoff values for Iv events were 1.6-fold higher than those for Ic events and occurred 38 min earlier. Values for Etot and Ctot for Iv events were 19-36% and 1.5-fold higher than corresponding values for Ic events. Values for Emax and Cmax for Iv events were 3-fold and 4-fold higher than corresponding values for Ic events. Carbon enrichment ratios (CER) were or=1.0 for CT plots (except for first 20 min). Maximum CER for CT-Ic, CT-Iv, ST-Ic, and ST-Iv were 2.0, 2.2, 1.0, and 1.2, respectively. Transport of sediment, carbon, and agrichemicals would be better understood if variable rainfall intensity patterns derived from natural rainfall were used in rainfall simulations to evaluate their fate and transport from CT and ST systems.

Nitrogen and phosphorus runoff losses from variable and constant intensity rainfall simulations on loamy sand under conventional and strip tillage systems.

Further studies on the quality of runoff from tillage and cropping systems in the southeastern USA are needed to refine current risk assessment tools for nutrient contamination. Our objective was to quantify and compare effects of constant (Ic) and variable (Iv) rainfall intensity patterns on inorganic nitrogen (N) and phosphorus (P) losses from a Tifton loamy sand (Plinthic Kandiudult) cropped to cotton (Gossypium hirsutum L.) and managed under conventional (CT) or strip-till (ST) systems. We simulated rainfall at a constant intensity and a variable intensity pattern (57 mm h(-1)) and collected runoff continuously at 5-min intervals for 70 min. For cumulative runoff at 50 min, the Iv pattern lost significantly greater amounts (p < 0.05) of total Kjeldahl N (TKN) and P (TKP) (849 g N ha(-1) and 266 g P ha(-1) for Iv; 623 g N ha(-1) and 192 g P ha(-1) for Ic) than did the Ic pattern. However, at 70 min, no significant differences in total losses were evident for TKN or TKP from either rainfall intensity pattern. In contrast, total cumulative losses of dissolved reactive P (DRP) and NO3-N were greatest for ST-Ic, followed by ST-Iv, CT-Ic, and CT-Iv in diminishing order (69 g DRP ha(-1) and 361 g NO3-N ha(-1); 37 g DRP ha(-1) and 133 g NO3-N ha(-1); 3 g DRP ha(-1) and 58 g NO3-N ha(-1); 1 g DRP ha(-1) and 49 g NO3-N ha(-1)). Results indicate that constant-rate rainfall simulations may overestimate the amount of dissolved nutrients lost to the environment in overland flow from cropping systems in loamy sand soils. We also found that CT treatments lost significantly greater amounts of TKN and TKP than ST treatments and in contrast, ST treatments lost significantly greater amounts of DRP and NO3-N than CT treatments. These results indicate that ST systems may be losing more soluble fractions than CT systems, but only a fraction the total N (33%) and total P (11%) lost through overland flow from CT systems.

Agitation in Alzheimer's disease is a manifestation of frontal lobe dysfunction.

OBJECTIVES: (1) To investigate the prevalence and characteristics of agitation in patients with Alzheimer's disease (AD) and other forms of dementia; (2) to explore the association between agitation and other clinical variables, including disease severity, functional impairment and other neuropsychiatric symptoms, and (3) to determine the predictors of agitation. METHODS: Data for 427 men and women with dementia from outpatient clinics of the University of California, Los Angeles Alzheimer's Disease Center were analyzed. There were 277 patients with AD, 43 with vascular dementia, 47 with mixed dementia, 45 with frontotemporal dementia and 15 with dementia with Lewy bodies. Patients were evaluated with the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Functional Activities Questionnaire (FAQ), neuropsychological tests and the Caregiver Appraisal instrument. SPSS10 was utilized for statistical analysis. RESULTS: There was no difference in agitation subscale scores among patients with dementia of various etiologies. In patients with AD, there was increased prevalence of agitation with increasing dementia severity. Agitation contributed substantially to caregiver burden and impact. There was a significant correlation between the FAQ and the NPI agitation subscale score after adjusting for MMSE scores. Delusion, disinhibition and irritability subscale scores in AD patients were correlated with agitation across disease severity. Subscale scores of frontally mediated behaviors including irritability, delusions and disinhibition predicted most of the variance in agitation levels. CONCLUSION: Agitation is common in AD and other dementias and has a marked impact on caregivers. It is related to dementia severity and to specific types of associated psychopathology implicating frontal lobe dysfunction. The present study is the largest and most comprehensive assessment of agitation reported. The data suggest that agitation in AD is a frontal lobe syndrome. Frontal lobe dysfunction may predispose AD patients to agitation by exaggerating behavioral responses to many types of coexisting psychopathology or environmental provocations.

Comparison of pattern of breathing with other measures of induction of anaesthesia, using propofol, methohexital, and sevoflurane.

We assessed change of the pattern of breathing as a marker of induction of anaesthesia, using a method of maintaining spontaneous breathing throughout the induction period. We compared this index with a measure used clinically, the lash reflex, and measures used for drug investigations such as loss of grip of an object, cessation of finger tapping, and loss of arm tone. Ninety female patients (mean age 32 (17-63) yr, mean weight 63 (10) kg) were randomly allocated to induction of anaesthesia using propofol, methohexital, or sevoflurane. The i.v. agents were given by slow injection estimated to give an induction dose (for weight drop end point) in 90 s. Sevoflurane was given by progressively increasing the inhaled concentration to 8% so that induction should occur within 90-120 s. We measured time to change in breathing pattern, loss of voluntary finger tapping, loss of the lash reflex (tested at 15 s intervals), loss of postural tone in an outstretched arm, and loss of grip of a small metal cylinder held between finger and thumb. For methohexital and sevoflurane, the mean times for induction of anaesthesia occurred in the above order. With propofol, the lash reflex and tone were lost at the same time. The mean (SD) time to induction, by loss of arm tone was 64 (16) s for propofol, 83 (23) s for methohexital, and 94 (31) s for sevoflurane. The mean time to change in breathing pattern was 47 (20) s for propofol, 53 (14) s for methohexital, and 78 (29) s for sevoflurane. Although the time to achieve each end point was different, all the end points (except the lash reflex) appeared to provide similar measures of induction of anaesthesia. The pattern of breathing is an early sign of the onset of anaesthesia.

Cocaine use, hypertension, and end-stage renal disease.

Cocaine use has been associated with both acute renal failure and hypertension (HTN), but only recently have data suggested it may lead to a chronic insidious form of renal failure. We designed a cross-sectional study to compare the association of cocaine use in hemodialysis patients with and without a diagnosis of HTN-related end-stage renal disease (HTN-ESRD). Two hundred one black patients from two outpatient hemodialysis units in an urban community were evaluated. There were 193 eligible patients, 106 men and 87 women, aged 49.28 +/- 14.4 years. A history of significant cocaine use before dialysis was reported by 55 of 193 subjects (28.5%). A diagnosis of HTN-ESRD was reported in 49 of 55 cocaine users (89.1%) compared with 64 of 138 nonusers (46.38%; odds ratio, 9.44; 95% confidence interval, 3.79 to 23.49; P < 0.0005). Of the 113 subjects with HTN-ESRD, 49 subjects (43.4%) had a history of cocaine abuse, either alone or in combination with other drugs. Subjects with HTN-ESRD with cocaine use were younger than those without cocaine use (40.7 +/- 9.0 versus 53.8 +/-15.3 years; P < 0.0005) and had a shorter reported duration of HTN (5.3 +/- 5.4 versus 12.7 +/- 9.8 years; P < 0.0005, adjusted for age and sex). In our urban dialysis population, a clinical diagnosis of HTN-ESRD was strongly associated with a history of cocaine use and earlier onset of ESRD. Cocaine should be considered as a cause of ESRD in patients without a clear cause of renal failure.

Gender effects on persistent cerebral metabolite changes in the frontal lobes of abstinent cocaine users.

OBJECTIVE: Previous studies found functional changes in the frontal brain region and regions with projections to the frontal lobe in cocaine users. The aim of this study was to investigate persistent neurochemical changes in the frontal lobes of subjects with a history of crack cocaine dependence and to determine whether these changes are different in male and female users. METHOD: The frontal gray and white matter of 64 young asymptomatic and abstinent (> 5 months) cocaine users (34 male and 30 female) and 58 healthy comparison subjects without a history of drug abuse was evaluated with localized proton magnetic resonance spectroscopy (1H-MRS). RESULTS: Two-way analysis of variance showed significant cocaine effects on the concentration of frontal gray matter N-acetyl compounds, on the ratio of frontal white matter N-acetyl compounds to creatine levels, on frontal gray and white matter myoinositol levels, and on the ratio of myoinositol to creatine. Significant gender effects were observed for frontal gray matter choline-containing compounds, the ratio of choline-containing compounds to creatine, and the percentage of CSF in both gray and white matter. Interaction effects of cocaine and gender were observed for creatine, N-acetyl/creatine ratio, and myoinositol/creatine ratio in frontal white matter. CONCLUSIONS: Cocaine use is associated with neuronal injury (with decreased N-acetyl compounds) in the frontal cortex and glial activation (with increased myoinositol) in both frontal gray and white matter. In the frontal lobe, cocaine affects male users differently than female users. Future studies on the effects of cocaine abuse should control for the effects of gender-specific neurotoxicity.

Conference presentations with confidence.

Remember that great presentation you heard at last year's convention? Perhaps the marketing case study was especially interesting. Or perhaps you wondered whether you could use the organizational tools the speaker described in your own work. Finally, you might have wondered, "Could I offer a conference presentation at some point?" The answer: yes!

Management of tumor lysis syndrome with standard continuous arteriovenous hemodialysis: case report and a review of the literature.

Tumor lysis syndrome (TLS) is a critical illness with few treatment options. This report describes the clinical course of a patient with non-Hodgkin's lymphoma, who developed TLS and required renal replacement therapy. Institution of the standard therapeutic approach, intermittent hemodialysis, was not possible because of persistent hypotension. Instead, the patient was treated with a short course of continuous arteriovenous hemofiltration (CAVH) and conventional continuous arteriovenous hemodialysis (CAVHD) with dialysate flow rate of 1 L/h), which resulted in effective control of serum uric acid, potassium, urea nitrogen, phosphorus, and extracellular fluid volume. This case is in distinction to a previous report of TLS treatment with CAVHD using 4 L/h dialysate flow rate. We conclude that continuous renal replacement therapies with standard dialysate flow rates and replacement volumes should be considered for the treatment of TLS, particulary if the syndrome is accompanied by hypotension.

Neurobiology of cocaine-induced organic brain impairment: contributions from functional neuroimaging.

The present review is directed at imparting the current knowledge regarding functional neuroimaging as a tool for enhancing the understanding of cerebrophysiologic and neurobehavioral consequences of stimulant abuse. Stimulants like cocaine are capable of inducing clinically significant neurocognitive impairment through direct action on the brain, and indirectly through other organs that influence cerebral physiology. Neurochemical dysregulation including profound effects on the serotonergic and dopaminergic systems have substantial physiological and neurobehavioral consequences. Brain hemorrhages, transient ischemic attacks, strokes,and seizures frequently follow cocaine use. The residual cerebropathologic consequences of cocaine are seen only in significant or pronounced brain events when structural neuroimaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) are employed. However, recent research with newer functional neuroimaging techniques such as single photon emission, positron emission tomography, and quantitative electroencephalography have revealed high rates of significant alteration in brain function among cocaine users, with negative structural imaging studies. These findings are often associated with impairment on neuropsychological evaluation, also in the absence of positive findings on CT and MRI. Both cerebral metabolic and hypoperfusion anomalies are seen, especially in anterior and temporal brain regions. Observed changes can persist for months, and for some patients, may represent a permanent change in brain functioning.

The role of fine-needle aspiration biopsy and flow cytometry in the evaluation of persistent neck adenopathy.

BACKGROUND: The role of fine-needle aspiration biopsy (FNAB) and flow cytometry (FCM) in the evaluation of persistent neck adenopathy has not been completely defined. METHODS: All patients who underwent FNAB of an abnormal lymph node from 1990 to 1997 were identified, and the results of FNAB and FCM were correlated with histology or clinical follow-up. RESULTS: FNAB was performed on 133 patients with an abnormal lymph node in the neck. FNAB was malignant in 82 (62%), atypical in 13 (10%), benign in 27 (20%), and nondiagnostic in 11 (8%) patients. FNAB was compared with histologic results in 114 (86%) or with the results of clinical follow-up (average 17 months) in 12 patients (9%). Seven patients (5%) were lost to follow-up. Lymphoma and metastatic carcinoma were diagnosed in 25 (19%) and 76 (57%) patients, respectively. Sensitivity of FNAB and FCM was 96% and 100%, respectively, and specificity was 58% and 100%, respectively. Patients with Hodgkin's lymphoma accounted for 80% of false negative FCM results. FCM was nondiagnostic in 3 of 34 patients (9%). Definitive subclassification of lymphoma was accomplished in only 3 of 17 (18%) patients in whom FCM was performed. CONCLUSIONS: FNAB is reliable in identifying metastatic disease, non-Hodgkin's lymphoma, and reactive lymphadenopathy in the neck. FNAB and FCM still have a limited role in definitive diagnosis of Hodgkin's lymphoma and classification of non-Hodgkin's lymphoma, underscoring the importance of excisional biopsy.

A review of the neuropsychological effects of commonly used prescription medications.

The practice of clinical neuropsychology has traditionally accorded limited attention to the impact of prescription medications on cognitive functioning. Though neuropsychologists see a wide array of patients with cerebropathologic and other organ system disease that are under pharmacotherapy, systematic attention to how these compounds potentially affect neuropsychological functioning has lagged. Psychomotor functioning, concentration, and memory are the most common cognitive domains negatively affected by such medications. In general sedative, psychomotor, and, to a lesser extent, attention/concentration effects covary and typically show tolerance with sustained drug administration. Memory effects are more resistant probably due to ongoing anticholinergic effects and the established link between the cholinergic system and memory functioning. This review covers the basic science and clinical literature addressing neuropsychological functioning both in healthy nonpatients and in patients treated with antidepressants, anxiolytics, stimulants, antihypertensives, antiepileptics and antihistamines. Critical to the understanding of the effects of these agents is the integration of multiple factors that modulate medication-induced neurocognitive effects, such as chronicity of treatment, tolerance, age, ethnicity, metabolic capacity, psychological, and neurological disorders in the patient, and the benefits of successful treatment of these disorders.

The pharmacologic treatment of anxiety and depression in African Americans. Considerations for the general practitioner.

A growing pool of recent research points to the importance of ethnicity in psychopharmacologic management of depression and anxiety disorders, with sometimes profound implications for efficacy and safety. Such research has provided provocative findings that illustrate important interethnic pharmacogenetic, pharmacokinetic, and pharmacodynamic differences, especially for African Americans. We did a systematic literature review of psychopharmacologic treatment considerations among African Americans with anxiety and mood disturbance seen by primary care physicians, who provide most psychopharmacologic treatment. The findings commonly point to a greater percentage of "poor metabolizers" among African Americans compared with Euro-Americans. General treatment considerations include greater attention to adverse effects and better clinical response and poorer compliance for a given dose, potential need for lower starting doses and slower increases, use of plasma drug levels if available, determination of past responses to a similar drug, and integration of pharmacogenetic information into an overall socioculturally and ethnically sensitive approach to assessment and treatment.