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Eliciting neutralizing antibodies is thought to be a key activity of a vaccine against human immunodeficiency virus (HIV). However, a number of studies have suggested that in addition to neutralization, interaction of IgG with Fc gamma receptors (FcγR) may play an important role in antibody-mediated protection. We have previously obtained evidence that the protective activity of the broadly neutralizing human IgG1 anti-HIV monoclonal antibody (MAb) b12 in macaques is diminished in the absence of FcγR binding capacity. To investigate antibody-dependent cellular cytotoxicity (ADCC) as a contributor to FcγR-associated protection, we developed a nonfucosylated variant of b12 (NFb12). We showed that, compared to fully fucosylated (referred to as wild-type in the text) b12, NFb12 had higher affinity for human and rhesus macaque FcγRIIIa and was more efficient in inhibiting viral replication and more effective in killing HIV-infected cells in an ADCC assay. Despite these more potent in vitro antiviral activities, NFb12 did not enhance protection in vivo against repeated low-dose vaginal challenge in the simian-human immunodeficiency virus (SHIV)/macaque model compared to wild-type b12. No difference in protection, viral load, or infection susceptibility was observed between animals given NFb12 and those given fully fucosylated b12, indicating that FcγR-mediated activities distinct from FcγRIIIa-mediated ADCC may be important in the observed protection against SHIV challenge.

OBJECTIVE: This study examined the experiential factors and interacting vulnerabilities that contribute to the development of posttraumatic stress disorder (PTSD) in children and adolescents. METHOD: Of 100 consecutive referrals to an inner-city child and adolescent psychiatry clinic, 59 had experienced a trauma that qualified as a precipitant of PTSD. For those with trauma, ages ranged from 3 to 18 years (mean=9.9, SD=4.10); 39 (66%) were males. The authors used a series of multiple regression analyses to examine the contribution of demographic characteristics, the nature of the stressor(s), and the role of preexisting clinical signs in the development of PTSD. RESULTS: Twenty-two percent of the 59 children who had been traumatized met full criteria for PTSD, 32% had some symptoms of PTSD but did not meet full criteria, and 46% had no symptoms of PTSD. Witnessing domestic violence or being physically abused predicted severity of PTSD. Children with preexisting aggressive behavior were more likely to be victims of physical abuse. CONCLUSIONS: Traumatic experience interacts with factors in the child and family to contribute to the development of PTSD. Trauma that threatens family integrity appears to make a strong contribution to the development of PTSD. Increased understanding of the factors contributing to PTSD may provide additional opportunities for developing effective interventions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study was designed to evaluate the comparative efficacy and safety of sertraline and nortriptyline for the treatment of major depressive disorder in older adults. METHOD: A double-blind, parallel group design was used to compare 210 outpatients, 60 years of age and older, who met DSM-III-R criteria for major depressive episode and had a minimum Hamilton Depression Rating Scale score of 18. The patients were randomly assigned to 12 weeks of treatment with either sertraline (50-150 mg/day) or nortriptyline (25-100 mg/day). RESULTS: The safety profiles of the two treatments were similar except that nortriptyline treatment was associated with a significant increase in pulse rate, whereas sertraline was associated with a nonsignificant decrease. Efficacy of both drugs was similar for both treatments at all time points, with 71.6% (N=53 of 74) of the sertraline-treated patients and 61.4% (N=43 of 70) of the nortriptyline-treated patients achieving responder status by week 12. Time to response was also similar, with more than 75% of the improvement in scores on the Hamilton depression scale having occurred by week 6. Secondary efficacy measures (posttreatment measures of cognitive function, memory, and quality of life) revealed a significant advantage for sertraline treatment. CONCLUSIONS: Primary efficacy measures showed sertraline and nortriptyline to be similarly effective. With secondary outcome measures there was consistent evidence of an advantage for the sertraline-treated group. The clinical impact of these measures on the long-term well-being of elderly depressed patients should be examined in a study of maintenance treatment. [ABSTRACT FROM AUTHOR]

Ample clinical and epidemiologic evidence exists to implicate homocyst(e)ine as a risk factor for atherosclerotic vascular disease and thrombosis. The precise mechanisms by which this occurs are uncertain but probably involve injury to endothelium, impairment of endothelial function, lipid peroxidation, oxidation of low-density lipoprotein, and creation of a prothrombotic environment in areas of endothelial injury. Plasma homocyst(e)ine concentration (PHC) can be effectively reduced with oral administration of folic acid. Whether vitamins B6 and B12 are also required in the absence of vitamin deficiency remains uncertain. Studies currently in progress may help to determine whether reduction of PHC will translate into a decrease in clinical vascular events. [ABSTRACT FROM AUTHOR]

The article presents a study regarding vocal acoustic correlates of flat affect in schizophrenia. The affect is similar to Parkinson's disease, right hemisphere disease and contrast with depression. The study concluded that affects, moods, and emotions are separate processes and that it is useful to maintain the distinction. Disturbances in various processes appear to have discrete aetologies and to require different treatments. There is a view that it might be better to start with new words to describe the different processes.

The treated one-year prevalence and point-prevalence of schizophrenia, schizoaffective psychosis, and paranoid state in the city of Salford were derived from the Salford Psychiatric Case Register. The high rates found are attributed primarily to the effects of selective migration from the area. A breakdown of the use of health services in the area by patients with these diagnoses is given; hospital care was found to be the major form of treatment. [ABSTRACT FROM AUTHOR]