Infectivity enhancement by HIV-1 Nef is dependent on the pathway of virus entry: implications for HIV-based gene transfer systems.

Retroviruses have been extensively used in the development of gene transfer systems. Recently, there has been a great deal of interest in the use of lentiviruses for gene transfer because they infect nondividing cells. Human immunodeficiency virus (HIV) has been the lentivirus most often used for this purpose, but its genomic complexity and limited tropism present some challenges to the establishment of efficient gene transfer systems. In this paper we present data showing intrinsic differences between the infectivity of wild-type HIV and HIV particles pseudotyped with heterologous envelope glycoproteins. Interestingly, HIV pseudotypes with envelope glycoproteins from the amphotropic murine leukemia virus or the vesicular stomatitis virus (VSV) are 3 and 40 times more infectious than wild-type HIV, respectively. In addition, we show that the reliance on Nef expression for maximal infectivity of HIV particles is dependent on the path of virus entry. The dependence on Nef for higher infectivity is greater for amphotropic pseudotypes and wild-type HIV than for VSV-G pseudotypes. We conclude that VSV-G pseudotypes of HIV vectors are an excellent choice for gene transfer purposes and Nef-mediated viral infectivity enhancement is affected by virus entry pathway.

Correlation of severity of psychiatric patients' delusions with right hemispatial inattention (left-turning behavior).

Studies associate psychotic disorders with various forms of subtle inattention to the right hemispace (left-turning behavior). The authors examined the correlation between this dopamine-related sign and severity of delusions (presumably dopaminergic symptoms) in 20 psychotic patients. Delusions were significantly correlated with severity of left-turning bias, and this neurological sign accounted for 33% of the variance in severity of delusions.

Behavioral changes in pediatric intensive care units.

OBJECTIVE: The purposes of this study were to compare the frequency and severity of manifestations of anxiety, depression, delirium, and withdrawal in pediatric patients hospitalized in intensive care unit vs ward settings and to evaluate the impact of preexisting psychopathologic disorders on the expression of these symptoms. RESEARCH DESIGN: Prospective patient series. SETTING: Tertiary care pediatric center. PATIENTS: Forty-three subjects aged 6 to 17 years hospitalized in either the pediatric or cardiovascular intensive care unit (n = 18) or on the general wards (n = 25) were recruited to participate. Subjects were excluded if their parents were unavailable for diagnostic interview or if they could not answer interview questions themselves. SELECTION PROCEDURES: Consecutive sample. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The Hospital Observed Behavior Scale, developed for this study, was used to describe objectively subjects' manifestations of anxiety, depression, delirium, and withdrawal. The Diagnostic Interview for Children and Adolescents and Diagnostic Interview for Children and Adolescents-Parents were used to determine the presence of preexisting psychopathologic disorders. As measured by the Hospital Observed Behavior Scale, subjects in the intensive care unit exhibited apprehension, anxiety, detachment, sadness, and weeping more often than did patients in the ward. Behavior was also significantly influenced by severity of illness, duration of hospitalization, number of previous hospitalizations, and presence of a preexisting anxiety or mood disorder. We found the Hospital Observed Behavior Scale to have good interrater reliability. CONCLUSIONS: Our data indicate that critically ill children in the intensive care unit, children with prolonged or repeated hospitalizations, and children with preexisting anxiety and mood disorders are at greater risk than other hospitalized pediatric patients for psychological trauma and/or behavior problems that may warrant psychiatric intervention. The Hospital Observed Behavior Scale is a reliable tool to quantitate behaviors in hospitalized children.

Psychiatric comorbidity and response to two doses of methylphenidate in children with attention deficit disorder.

ABSTRACT In a large, heterogeneous sample (N = 182) of children with attention deficit disorder (ADD), the prevalences of additional DSM-III diagnoses were determined using the Diagnostic Interview for Children and Adolescents (DICA). More than half the children had additional DSM-III psychiatric diagnoses. Oppositional disorder and anxiety/mood disorders were the most frequent diagnoses. White male children with ADD were selected into four contrast groups based on comorbidity: ADD children with no additional diagnosis (neither), with anxiety or depression (ANX/DEP), with oppositional or conduct disorder (OPP/CON), and with both ANX/DEP and OPP/CON diagnoses (both). ADD children who had both ANX/DEP and OPP/CON were significantly more improved on a high dose (0.6 mg/kg bid) than a low dose (0.3 mg/kg bid), but ADD boys in the other diagnostic groups responded as well to both doses. There was no evidence that ADD children with comorbid emotional or disruptive behavior disorders respond any less well to psychostimulants than other ADD children. However, there is a concern for those children who have the comorbid combination of (1) ADD, (2) an additional externalizing disorder (disruptive behavior disorder), and (3) an internalizing disorder (a mood or anxiety disorder). These children may not respond to low clinical doses of psychostimulants, but may respond well at higher doses. Children's self-ratings on the DICA may provide important clinical data concerning stimulant dosing which are not provided by teacher or parent ratings. We found no evidence that ADD children with comorbid emotional disorders respond any less well to a psychostimulant than ADD children without emotional comorbidity.

The frequency and significance of additional self-reported psychiatric diagnoses in children with attention deficit disorder.

The frequency of additional self-reported diagnoses in a large, heterogeneous sample of attention deficit disorder (ADD) children (N = 182) was determined using the Diagnostic Interview for Children and Adolescents (DICA). Over half the children had additional DICA diagnoses, with oppositional disorder and anxiety/mood disorders the most frequent. ADD boys with internalizing-type diagnoses had lower verbal IQs and arithmetic scores and performed more poorly on attention tasks than those without; parents also rated them more adversely. Those with externalizing-type diagnoses were rated as more aggressive by teachers and had sociopathic, thrill-seeking profiles on paper-pencil self-ratings. Over 40% of the children were dyslexic or slow learners but they had no higher rate of DICA diagnoses than those who read adequately.

Identifying psychiatric disorders in children with renal disease.

We gave a structured diagnostic interview to determine what psychiatric disorders were present in 15 children aged 8 to 16 years who had renal disease; eight of the children had end-stage renal disease, and the seven children in the control group had mild renal disease. We calculated the psychiatric disorders diagnosed, and compared the results between the two groups. Depression was the most common psychiatric disorder in the children with end-stage renal disease (N = 5), while anxiety disorders were the most common psychiatric problem in the group having mild renal disease (N = 4). We discuss possible explanations for the psychiatric disorders in each group, as well as future research directions.

Somatization disorder in men.

Somatization disorder is thought to be rare in men. This paper reviews five previously reported cases of somatization disorder in men and reports nine new cases referred from primary care physicians. These men have most of the associated features of the disorder, are of lower socioeconomic status, and have other significant psychiatric diagnoses. Eight of the nine men had a dramatic precipitating event at the onset of their illness. This diagnosis appears to be applicable to men and needs to be considered in men with multiple, recurrent unexplained medical symptoms.

Tricyclic antidepressants and delirium.

Some patients who take tricyclic antidepressants (TCAs) develop delirium. Charts were reviewed of 125 inpatients whose TCA plasma levels had been assayed. Delirium was documented in 10 cases. The occurrence of delirium was statistically related to age, race, and loge plasma TCA levels.

B12 deficiency and psychiatric disorders: case report and literature review.

Although an association of psychiatric symptoms with vitamin B12 deficiency is well accepted, the incidence and nature of these symptoms is not established. To help illuminate the natural history of this illness we review the literature regarding psychopathology associated with B12 deficiency and examine 15 cases, including one of our own, that meet specified criteria for B12-responsive psychosis. In the accepted cases the most common psychiatric symptoms were organic brain syndrome, paranoia, violence, and depression. Several of the patients were not anemic and had no neurologic deficit. Examination of blood smears or obtaining of serum B12 levels should be considered for patients with the symptoms described.