Risperidone and cognitive function in children with disruptive behavior disorders.

BACKGROUND: Effects of risperidone on cognitive function in children with disruptive behavior disorders (DBDs) and subaverage intelligence quotient (IQ) were assessed. METHODS: Data from two 6-week, double-blind, placebo-controlled studies (n = 228) were combined, as were three 1-year, open-label studies (n = 688). Patients with DBDs and subaverage IQ, 5 to14 years, received placebo or risperidone .02 to .06 mg/kg/day. Cognitive measures included the Continuous Performance Task (CPT) and Verbal Learning Test for Children (VLT-C). Efficacy was assessed using the Nisonger Child Behavior Rating Form (NCBRF). Adverse events were collected via spontaneous report; sedation was assessed using visual analog scale. RESULTS: Improvements on the NCBRF Conduct Problem subscale were significantly greater for risperidone- versus placebo-treated patients (-15.8 vs. -6.4, p < .0001) in short-term studies; significant reductions were observed in long-term studies (-16.3, p < .0001). No overall decline and some significant improvement in attention (CPT) and memory (VLT-C) were noted regardless of treatment in short-term studies. VLT-C improved significantly (p < .0001) for both groups, with no difference between treatment groups. Improvements in memory (VLT-C) and attention (CPT) were noted in long-term studies. Somnolence/sedation did not affect cognitive function. CONCLUSIONS: Cognitive function was not altered by risperidone in short-term studies and was maintained or improved with one year of treatment in children with DBDs and subaverage IQ, potentially representing age-appropriate gains.     

Behavior of children with seizures. Comparison with norms and effect of seizure type.

Scores for 112 children aged 6 to 12 years, with well-controlled seizures and of average or higher IQ, were compared for problem behavior with established norms. As assessed on the Conners' Teacher Rating Scale, the group with seizures was comparable to the normative group on two subscales and superior on two others. In contrast, parents of children in the seizure group rated them as significantly worse on all six subscales of the Revised Behavior Problem Checklist. In a larger group of 133 children with seizures, from which this sample was selected, the relationship of age, sex, and seizure type to behavior problems was examined. Subjects with partial seizures were rated as slightly more aggressive and antisocial than those with generalized seizures. Findings were discussed in regard to differences in perception of behavior by parents and teachers and the possible relevance of seizure type to the expression of behavior problems.     

Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch Type (HCHWA-D): I - A Review of Clinical, Radiologic and Genetic Aspects

Hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of β-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma.
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article     

TPA (12-O-tetradecanoyl-phorbol-13-acetate) activation and differentiation of human peripheral B lymphocytes

The effect of the tumour-promoting phorbol ester TPA (12-O-tetradecanoyl-phorbol-13-acetate) on normal human peripheral blood and tonsil B lymphocytes was investigated. A strong DNA-synthesis response with the maximum at day 4 was detected. This response was, however, inhibited by increasing concentrations of serum in the medium. The membrane Ig expression was changed with a rapid decrease in IgD expression and a slower decrease in IgM and IgG expression. TPA-induced Ig secretion was detected in 12 out of 22 tested donors and the response was found to be independent of T cells and macrophages. The expression of four monoclonal antibody-detected B cell activation and differentiation markers, B1, B2, LB1 and BB1, was followed. The results indicate activation and differentiation of the B cells.     

Autonomic nerve function in children and adolescents with insulin-dependent diabetes mellitus.

Autonomic nerve function was assessed in 67 insulin-dependent diabetic children and adolescents and in 30 control subjects of the same age. The heart rate and blood pressure reactions to a deep breathing test (E/I ratio) and a tilt table test (acceleration and brake indices) were used. The E/I ratio, 1.54 +/- 0.21, and the acceleration index, 25 +/- 7.7, in the diabetic children were not significantly different from those of the control children, 1.51 +/- 0.16 and 24 +/- 7.5, respectively. Neither was any difference observed between the mean brake index values; 24.3 +/- 14.6 vs 23.5 +/- 7.5. However, the variance of the brake index in diabetic children was significantly higher than in control children (P less than 0.005). The brake index was negatively correlated to age in the healthy control children (r = -0.48, P less than 0.1). The acceleration index, but not the E/I ratio, also tended to be age related (r = -0.32, P less than 0.01 NS). No correlation was observed between sex, glycaemic control or duration of diabetes and the autonomic nerve function. Neither were severe hypoglycaemic episodes in diabetic children related to the autonomic nerve function. It is concluded that autonomic neuropathy is uncommon in diabetic children and adolescents and that age-related index values should be used when autonomic nerve function is evaluated in children of different ages.     

Caregiver perceptions of psychotropic medication in residential facilities

Direct caregivers (designated as "psychopaedic nurses" in New Zealand) in two public residential facilities were surveyed regarding their perceptions, opinions, and knowledge of psychotropic drugs. Of 276 individuals contacted, 227 (82%) returned usable questionnaires. The results indicated that unit supervisors (charge nurses) and unit doctors were perceived as wielding most influence on decisions regarding psychotropic drugs, whereas caregivers based outside residential units were seen as having little influence. Aggressive/destructive behavior and, to a smaller extent, self-injurious behavior were seen as the most likely problem behaviors to lead to medication use. Subjective measures were generally favored for assessing drug effects although, in a hypothetical "ideal" situation, nurses gave increasing priority to more objective indices. Endorsement of behavior modification as an alternative to pharmacotherapy was generally high. A large majority of these caregivers (85%) expressed dissatisfaction with their training concerning psychotropic drugs. Finally, data were presented on drug topics about which respondents wanted to learn more and about changes they wished to see instated in their facilities. Our principal conclusion was that these data indicate a need for more education on a variety of social, pharmacological, and behavioral issues as they relate to medication use.     

Preoperative transhepatic biliary decompression in pancreatic and periampullary cancer

Pancreatic resection for pancreatic and periampullary cancer between 1969 and 1975 at The Ohio State University Hospitals had an associated operative mortality rate of 30% and a morbidity rate of 80%. Transhepatic biliary decompression (THD) has been accepted as a method of preoperative risk reduction in the deeply jaundiced patient and an alternative to surgical biliary decompression. The use of preoperative THD in pancreatic and periampullary cancer was examined. Of 44 patients with bilirubin greater than 10 mg/100 ml, 17 had radical resection (THD=7, no THD=10), and 27 had palliative operation (THD=17, no THD=10). Preoperative serum bilirubin in the THD group was 7.3±1.0 compared to 16.3 ±1.5 in the no THD group (p < 0.05). Operative morbidity rate was: radical surgery: THD (40%), no THD (70%); palliative surgery: THD (18%), no THD (20%). Operative mortality rate was: radical surgery: THD (28%), no THD (60%); palliative surgery: THD (6%), no THD (0%). Catheter-related complications were minimal. Preoperative THD tends to reduce the risk of curative resection for pancreatic and periampullary cancer, but does not alter the outcome of palliative surgery. Long-term THD may be an alternative if palliative surgical biliary decompression either fails or is not technically possible in the patient with unresectable cancer.

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Resumen Se ha agudizado el debate relativo al papel de la resección curativa en el tratamiento del carcinoma pancreático y periampular. Mucha de la discusión se deriva de la excesiva morbilidad y mortalidad de la pancreatoduodenectomía y de la pancreatectomía total. Las cifras sobrepasan el porcentaje de supervivencia a 5 anos en todas las series mayores, y en algunos reportes la mortalidad operatoria es igual o mayor que el porcentaje de pacientes que sobreviven un año.La resección pancreática para cáncer pancreático y periampular entre los años 1969 y 1975 en los Hospitales de la Universidad del Estado de Ohio estuvo asociada con una mortalidad de 30% y una morbilidad de 80%. La descompresión biliar transhepática (DBT) ha sido aceptada como un método de reducción preoperatoria del riesgo quirúrgico en los pacientes intensamente ictéricos y como una alternativa a la descompresión biliar quirúrgica. El uso de la DBT preoperatoria en el cancer pancreático y periampular fué analizado. De 44 pacientes con bilirrubina mayor de 10 mg/100 ml, 17 fueron sometidos a resección radical (DBT = 7, no DBT = 10), y 27 tuvieron una operación paliativa (DBT = 17, no DBT = 10). La bilirrubina sérica en el grupo con DBT fué de 7.3±1.0, comparada con 16.3±1.5 en el grupo sin DBT (p < 0.05). La siguiente fué la morbilidad operatoria: cirugía radical: DBT 40%, no DBT 70%; cirugía paliativa: DBT 18%, no DBT 20%. La siguiente fué la mortalidad operatoria: cirugía radical: DPT 28%, no DPT 60%; cirugía paliativa: DBT 6%, no DBT 0. La DBT preoperatoria tiende a reducir el riesgo de la resección curativa para cáncer pancreático y periampular, pero no modiflca el resultado de la cirugía paliativa. La DBT prolongada puede ser una alternativa si la descompresión biliar quirúrgica falla o no es técnicamente posible en el paciente con cáncer no resecable.

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Résumé La résection pancréatique pour cancer périampullaire ou pour cancer du pancréas entre 1969 et 1975 à Ohio State University Hospital accuse une mortalité opératoire de 30% et une morbidité de 80%. Le drainage biliaire transhépatique (transhepatic biliary decompression: T.H.D.), en présence de ces résultats, a été employé à titre pré-opératoire pour diminuer les risques de l'intervention chez les malades très ictériques et comme alternative au drainage biliaire chirurgical.Chez 44 malades qui présentaient un taux de bilirubine supérieur à 10 mg/dl, 17 ont subi une exérèse (7 après drainage transhépatique, 10 sans drainage transhépatique), 27 ont été traités par une intervention palliative (17 après drainage, 10 sans drainage). Le taux de bilirubine pré-opératoire fut ramené à 7.3±10 chez les malades drainés alors qu'il atteignait 16.3± 1.5 chez les malades qui n'avaient pas subi de drainage préalable.La morbidité opératoire fut en cas de chirurgie radicale de 40% après drainage et de 70% en l'absence de drainage; en cas de chirurgie palliative elle fut de 18% après drainage et de 20% en l'absence de drainage. La mortalité opératoire fut en cas de chirurgie radicale de 28% après drainage et de 60% en l'absence de drainage; en cas de chirurgie palliative elle fut de 6% après drainage et de 0% en l'absence de drainage. Les complications du drainage sont très rares. En un mot le drainage biliaire pré-opératoire réduit les risques de l'exérèse des cancers pancréatiques et des cancers périampullaire mais elle est sans influence en cas d'intervention palliative. Le drainage biliaire transhépatique prolongé offre une alternative au drainage chirurgical lorsque celui-ci échoue ou quand le cancer ne peut être réséqué.