Diphenylhydantoin, Phenobarbital, and Primidone in Saliva, Plasma, and Cerebrospinal Fluid

Diphenylhydantoin, primidone, and phenobarbital were determined in saliva and plasma of 164 patients by gas-liquid chromatography. The saliva ratio was about one-tenth in patients on diphenylhydantoin, 0.32-0.38 on phenobarbital alone and with other drugs, 0.97 and 0.96 on primidone alone and with other drugs. The S/P ratio of phenobarbital was similar in patients treated with primidone alone or with co-medication. For diphenylhydantoin and primidone, the S/P and CSF/plasma ratio were similar; for phenobarbital the S/P ratio was lower due to the difference in pH of saliva and CSF. Thus the concentration in saliva serves as a measure of the nonprotein-bound or free concentration in plasma with the advantage that saliva is easy to obtain. Co-medication does not change the S/P ratio for the three drugs studied. The high correlation between levels in plasma and in saliva allows the plasma levels to be predicted from the concentration in saliva.     

Fasciitis, perimyositis, myositis, polymyositis, and eosinophilia

Several groups of cases of fasciitis and myositis with eosinophilia are reported. The common features are inflammation into fascia and/or perimysium, and/or muscle fibers; eosinophilia in blood and/or in muscle biopsy. The following classification of 24 cases is suggested: at one end of the spectrum are fasciitis with eosinophilia: diffuse fasciitis (Shulman syndrome): 10 cases (3 with hematological complications); 2 cases of diffuse fasciitis with muscle atrophy; 3 cases of restricted fasciitis. Relapsing perimyositis with eosinophilia belong to the same spectrum, either diffuse (5 cases) with myalgias, or localized (2 cases). Other cases are focal myositis or multiple myositis, polymyositis with eosinophilia. The relationship among these cases is discussed. There is a continuum among the different groups. The pathophysiology remains unknown.     

Caspases, apoptosis, and Alzheimer disease: causation, correlation, and confusion

Extensive neuron loss occurs in Alzheimer disease (AD) brain and some authors have speculated that dysregulation of apoptotic death pathways is etiologically responsible for the disease. Apoptosis is regulated in mammalian cells by a family of cysteine proteases called caspases. At least 7 different caspases (caspases 1, 2, 3, 6, 8, 9, and 12) have been implicated in regulating neuronal cell death in response to amyloid beta (A beta) exposure in vitro, in animal models of neurodegenerative diseases, and in AD brain itself. Despite this seemingly impressive array of data implicating caspases and apoptosis as etiologic factors in AD, the direct involvement of caspase-dependent neuronal apoptosis in AD pathogenesis remains uncertain. Alternative explanations for some findings, contradictory experimental observations, and lack of morphologically convincing apoptotic neurons in the vast majority of AD brains has led to the revised hypothesis that apoptosis-associated molecular events cause neuronal dysfunction in the absence of, or prior to, neuronal death. Unfortunately, this new view renders the term "apoptosis-associated" functionally meaningless since it bears no relationship with apoptotic death and fails to focus scientific investigation on the molecular insults that trigger the "apoptosis-associated" response in AD neurons. On balance, an etiologic role for caspases in AD is far from proven. It remains possible, however, that caspase-dependent neuronal death contributes to AD neuron loss and thus, caspase inhibition offers some hope for extending AD neuron survival so that other agents, targeting upstream events, may delay or reverse primary AD pathology.     

Head size and intelligence, learning, nutritional status and brain development. Head, IQ, learning, nutrition and brain

This multifactorial study investigates the interrelationships between head circumference (HC) and intellectual quotient (IQ), learning, nutritional status and brain development in Chilean school-age children graduating from high school, of both sexes and with high and low IQ and socio-economic strata (SES). The sample consisted of 96 right-handed healthy students (mean age 18.0 +/- 0.9 years) born at term. HC was measured both in the children and their parents and was expressed as Z-score (Z-HC). In children, IQ was determined by means of the Wechsler Intelligence Scale for Adults-Revised (WAIS-R), scholastic achievement (SA) through the standard Spanish language and mathematics tests and the academic aptitude test (AAT) score, nutritional status was assessed through anthropometric indicators, brain development was determined by magnetic resonance imaging (MRI) and SES applying the Graffar modified method. Results showed that microcephalic children (Z-HC < or = 2 S.D.) had significantly lower values mainly for brain volume (BV), parental Z-HC, IQ, SA, AAT, birth length (BL) and a significantly higher incidence of undernutrition in the first year of life compared with their macrocephalic peers (Z-HC > 2S.D.). Multiple regression analysis revealed that BV, parental Z-HC and BL were the independent variables with the greatest explanatory power for child's Z-HC variance (r(2) = 0.727). These findings confirm the hypothesis formulated in this study: (1) independently of age, sex and SES, brain parameters, parental HC and prenatal nutritional indicators are the most important independent variables that determine HC and (2) microcephalic children present multiple disorders not only related to BV but also to IQ, SA and nutritional background.     

Hopelessness,depression, substance disorder,and suicidality

Abstract. Background: Most earlier studies of hopelessness as a risk factor for suicidal behavior were based on either clinical or restricted samples. Using a longitudinal study design with a community sample of more than 3,000 participants, we aimed to examine if hopelessness was a long-term predictor of suicidal behaviors. Methods: Using longitudinal data from the Baltimore Epidemiologic Catchment Area (ECA) Program, we assessed the association of hopelessness at baseline and incident suicidal behaviors in the 13-year follow-up period, adjusting for the presence of depression and substance use disorders. Suicide behaviors studied included completed suicide, self-reported attempted suicide, and suicide ideation. Results: Hopelessness was predictive of all three types of suicidal behaviors in the follow-up period, even after adjustment. Persons who expressed hopelessness in 1981 were 11.2 times as likely to have completed suicide over the 13-year follow-up interval (95% confidence interval [1.8, 69.1]). The association between suicidality and hopelessness was stronger and more stable than the association of suicidality with the presence of depression and substance use disorders. Conclusion: Hopelessness was an independent risk factor for completed suicide, suicide attempts, and suicidal ideation. Intervention strategies that lower hopelessness may be effective for suicide prevention.Dr. Kuo is currently with Medical and Health Research Association (MHRA) and National Development and Research Institute, Inc (NDRI), New York, NY, USA. Dr. Gallo is currently with the Department of Family Practice and Community Medicine, University of Pennsylvania, Philadelphia, PA, USA.     

Language,meaning, context,and functional communication

Background : In the 1970s Audrey Holland first emphasised the importance of “functional communication” rather than “linguistic accuracy” for individuals with aphasia, noting that they could often “communicate” better than they could “talk”. Her approach inspired many to explore why and how this could be so, and to look for avenues that tapped everyday communication skills, rather than the person with aphasia's performance on decontextualised language tests.

Aims: This paper addresses the kinds of issues that are involved in “functional communication” and specifically addresses the role of language in this endeavour. It aims to highlight language as a set of “meaning-making resources” rather than as a set of syntactic/semantic constructs that exist outside of the communicator's everyday environment, that have to be mastered before being put into practice and that exist regardless of specific contexts.

Main Contribution: The paper discusses language's role in social life in which speakers not only convey information to each other but also maintain social relationships through communication. A taxonomy of the different kinds of social meanings that speakers use to communicate is proposed for use in aphasia research, based on the work of Halliday (1994 Halliday, M.A. K. 1994. An introduction to functional grammar, 2nd, London: Arnold.  [Google Scholar])—those related to conveying ideas and experiences (e.g., vocabulary related to particular experiences, topics), those related to interpersonal relationships (e.g., speech acts, evaluative language devices, exchange structure), and those related to maintaining continuity and coherence across the speaker's discourse (e.g., cohesion). In addition, the systematic relationship existing between language and context and its clinical implications are explored.

Conclusions: Language as information is only one form of language use. The paper argues for further consideration in aphasiology of the importance of multiple language uses and their relation to context. It is proposed that regarding language forms from these different perspectives of use will enable clinicians to further address the different aspects of communication required for meaningful and satisfying interactions in everyday social life.     

Caregiving,residence, race,and depressive symptoms

The objective of this study is to evaluate the psychological responses to caregiving between black and white dementia caregivers measured by self-reports of depressive symptoms evaluating the impact of sub-components of the Center for Epidemiologic Studies Depression Scale (CES-D) and residential arrangements of the caregiving dyad. The method included 87 intergenerational family caregivers enrolled in the Duke Caregiver Study (50 white and 37 black). Total CES-D and the four sub-components were modeled as dependent measures in separate linear regressions. Three models were examined. The first model tested race, living arrangements, and their interaction. The second model adjusted for age, gender, education, income, health status, cultural justification for caregiving, crime concerns, systolic blood pressure, diastolic blood pressure, and glycosylated hemoglobin. A third model added adjustment for caregiver burden. The results showed that there was a significant race by residence interaction for CES-D, somatic symptoms and depressive affect such that when the dyads are living apart–with the care recipient in their own home or in an institutional setting–whites reported more depressive symptoms than blacks. When the dyads lived together, this was reversed, and blacks reported higher depressive symptoms than whites. To conclude, all the parameters such as race, living arrangements, and the components of depression need to be taken into account to understand the impact of caregiving on the emotional health of caregivers.     

Sensation seeking,puberty, and nicotine,alcohol, and marijuana use in adolescence

OBJECTIVE: To examine the relationship among nicotine, alcohol, and marijuana use; level of sensation seeking (SS); and pubertal development. METHOD: Subjects were early and middle adolescent males and females recruited from a psychiatric clinic (n = 77) and two general pediatric clinics (n = 131). SS was measured by using the Sensation Seeking Scale for Children. Pubertal development was measured with a modified Pubertal Development Scale that was completed by the adolescent and his/her parent about the adolescent. Adolescent self-reports of nicotine, alcohol, and marijuana use were also obtained using questionnaires. RESULTS: SS was higher in males and females who reported nicotine and alcohol use and in males who reported marijuana use. SS was positively associated with pubertal development in males and females, even when controlling for age. Furthermore, SS mediated the relationship of pubertal development and drug use in males and females. CONCLUSIONS: The observation that SS mediates the relationship between pubertal development and drug use in males and females may contribute to understanding changes in drug use that are seen during adolescence. In addition, SS is associated with drug use and is easily measured in a variety of clinical settings.     

cAMP, tubulin, axonal transport, and regeneration

Mounting a regenerative response after injury is a multistep process for PNS neurons. The reason for failure of mammalian CNS neurons to regenerate successfully may involve more than one of those steps. Han et al. [Exp. Neurol. 189 (2004) 293] and others show that increasing cAMP levels in neuronal cell bodies elicits a partial regenerative response, altering expression of tubulin isotypes but not expression of other growth-associated genes or rate of axonal transport. This approach allows identification of specific steps in the regenerative response and the roles played by these steps.     

Alcohol, Seizures, and Epilepsy

Summary: Seizures, epilepsy, and alcohol are complexly interrelated. Although it is commonly perceived that patients with epilepsy experience problems with seizure control if they use alcohol, this is not confirmed by the few experimental studies that have tested the hypothesis. The last 30 years have emphasized the role of withdrawal from alcohol as a mechanism of seizure production. However, this is but one of many potential mechanisms by which seizures and epilepsy may be related to alcohol use and abuse. The rare but clear situations in which alcohol can act as a convulsant drug need further study, and mechanisms by which the long-term neurotoxic effects of alcohol lead to chronic epilepsy also need further elucidation.