No seizure exacerbation from risperidone in youth with comorbid epilepsy and psychiatric disorders: a case series

OBJECTIVE: The aim of this study was to study risperidone use in pediatric patients with comorbid epilepsy and psychiatric disorders. METHOD: We retrospectively reviewed the outpatient psychopharmacology medical records of patients with epilepsy, aged 19 and younger, who received risperidone for psychiatric disorders. RESULTS: Twenty-one (21) youths (mean age, 12.0 +/- 4.2 years) met our criteria for review. Mean risperidone dosage was 2.4 +/- 3.5 mg/day. Target symptoms included severe aggression, severe agitation, psychosis, and self-injurious behavior. Diagnoses included attention-deficit hyperactivity disorder (ADHD), learning disorder, and impulse control disorder. Seizure type was partial complex in 12 patients, generalized in 6 patients, neonatal in 1 patient, myoclonic in 1 patient, and unclassified in 1 patient. The average number of previous psychotropic trials was 3.5 +/- 3.0. Using a definition of response of a Clinical Global Impressions (CGI) improvement score of 2 or less, 15 patients (71%) were considered responders. Adverse effects were none to slight in 16 patients, moderate in 4 patients, and severe in 1 patient. Seizures did not worsen in any patient. CONCLUSIONS: Risperidone was associated with a clinically significant global improvement, without seizure exacerbation in youths with epilepsy and psychiatric disorders. Despite the limitations of the study design, the 71% responder rate is noteworthy in this treatment-refractory group.     

Anterior lenticonus: diagnostic aid in Alport syndrome

Anterior lenticonus is a rare condition in which the lens presents a conical protrusion of its anterior cortex. Sometimes isolated, it may be an ocular manifestation of Alport syndrome, a hereditary nephritis accompanied by deafness and other ocular signs such as flecked retinopathy or posterior polymorphous corneal dystrophy. All these manifestations are a result of a genetic defect in type IV collagen, a major component of basal membranes in the human body. The clinical aspects and therapy of anterior lenticonus and Alport syndrome are described, as well as the exploration that must begin when anterior lenticonus is discovered. This exploration is essential so that this diagnosis can be made as soon as possible.     

Design, synthesis, and anticancer properties of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone and analogues

4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) has recently completed a phase I clinical trial in advanced cancer with minimal toxicity, and impressive objective responses were noted. A-007 possesses three moieties that appear to have an influence on its anticancer activities: diphenylmethane, hydrazone, and dinitrophenyl. The goals of this study were to modify A-007's chemical moieties with the ultimate goal of maximizing its anticancer activity through increased planarity and introduction of functional groups. Thirty-five phenylhydrazone analogues of A-007 were synthesized and evaluated in vitro in a human primary cancer explant assay. Anticancer activities for selected analogues were also assayed for activity vs established human/murine cell lines. One-hundred-eighty-six fresh human solid tumors were used to screen for anticancer activity. Selected analogues were assayed for therapeutic indices (vs GM-CFC from bone marrow) in preparation for preclinical studies. Several polyaryl phenylhydrazones demonstrated improved cytotoxic activities by factors of 10(2)-10(3) when compared with A-007. However, the polyaryl quinone moieties of the latter analogues introduced potential toxic properties (cardiac, hematological) that do not exist with A-007.     

Clinical outcome after front-line intensive sequential chemotherapy (ISC) in patients with aggressive non-Hodgkin''s lymphoma and high-risk international prognostic index (IPI 3): final analysis of survival in two consecutive ISC trials.

Background:Aggressive non-Hodgkins lymphomas (NHL) in patients under the age of 60 have a very poor prognosis when the international prognostic index (IPI) is high, with an age-adjusted (Aa)-IPI score at 3. In such patients, conventional chemotherapy results in a low complete response (CR) rate of 46%, a five-year survival and disease-free survival (DFS) of 32% and 58%, respectively. For this report we have analyzed whether front-line high-dose chemotherapy could influence the outcome of this group of patients. Patients and methods:From 1992 onwards we conducted two pilot clinical trials of intensive sequential chemotherapy (ISC) with growth factors and blood stem cell support as initial treatment in 62 poor-risk patients with aggressive NHL. Of these patients, 33 were considered to be a high-risk group based on the Aa-IPI. Results:The median age was 42 years (range 21–60). The treatment was completed in 88% of patients, 86% receiving greater than 75% or more of the projected dose-intensity. Twenty patients (61%) achieved a CR. At a median follow-up of 48 months (range 26–86), the estimated five-year survival and DFS was 51% (95% confidence interval (CI): 34%–68%) and 70% (95% CI: 50%–90%), respectively. Conclusion:These results suggest that primary treatment using high-dose therapy supported by both growth factors and peripheral blood stem cells can cure up to 50% of high-risk patients with malignant lymphomas.