Treatment practices for childhood posttraumatic stress disorder.

OBJECTIVE: This study surveyed practices in treating childhood PTSD among child psychiatrists and non-M.D. therapists with self-identified interest in treating traumatized children. METHOD: An anonymous survey was mailed to 207 child psychiatrists ("medical") and 460 nonphysician ("non-medical") therapists inquiring about current interventions used to treat children with PTSD. RESULTS: Two hundred and forty-seven responses were received: of 77 medical and 82 nonmedical respondents who currently treat children with PTSD, a wide variety of modalities are used. Most preferred modalities among medical responders were pharmacotherapy, psychodynamic, and cognitive-behavioral therapy. Most preferred modalities among nonmedical respondents were cognitive-behavioral, family, and nondirective play therapy. Ninety-five percent of medical respondents used pharmacotherapy for this disorder; most preferred medications to treat childhood PTSD were selective serotonin reuptake inhibitors and alpha-adrenergic agonists. Several significant differences between medical and nonmedical practices were identified. CONCLUSIONS: There is little clinical consensus regarding the effectiveness of the many modalities used to treat traumatized children who have PTSD symptoms; empirical research is particularly needed to evaluate the efficacy of pharmacotherapy and EMDR.

The importance of culture in treating abused and neglected children: an empirical review.

There is growing evidence that cultural factors may influence symptom development and treatment referral patterns among abused and neglected children. To date, few treatment outcome studies have specifically examined the impact of race, culture, or ethnicity on treatment response among maltreated children. Those that have attempted to include these factors have typically suffered from lack of clarity of the meaning of these terms. This article reviews the available empirical evidence that addresses the influence of culture on symptom formation, treatment-seeking behaviors, treatment preference, and response following child maltreatment. Hypotheses regarding these findings are addressed, and implications for practice, research, and public policy are discussed.

Treatment for sexually abused children and adolescents.

The authors review research demonstrating the variable effects of childhood sexual abuse, the need for intervention, and the effectiveness of available treatment models. The well-controlled treatment-outcome studies reviewed do not focus on sensationalistic fringe treatments that treat sexually abused children as a special class of patients. Instead, studies demonstrate empirical evidence for extending and modifying treatment models from mainstream clinical child psychology to sexually abused children. The authors propose a continuum of interventions to meet the needs of this heterogeneous group. Interventions range from psychoeducation and screening, to short-term, abuse-focused cognitive-behavioral therapy with family involvement, to more comprehensive long-term plans for multiproblem cases. Last discussed are gaps in the research and suggestions for future research to address the pressing dilemmas faced by clinicians and policymakers.

Predictors of treatment outcome in sexually abused children.

PROBLEM: This study evaluated the impact of child and family characteristics on treatment outcome of sexually abused children. METHOD: Forty-nine recently sexually abused 7- to 14-year-old children were randomly assigned to either abuse-focused cognitive behavioral therapy or nondirective supportive therapy, and assessed pre- and post-treatment using several standardized instruments. These included five measures of psychological symptomatology and four measures of child and family characteristics hypothesized to mediate treatment response. Correlational and multiple regression analyses were utilized to evaluate the impact of the following mediating factors on treatment outcome: Children's abuse-related attributions and perceptions; family cohesion and adaptability; parental support of the child; and parental emotional reaction to the child's abuse. RESULTS: Children's abuse-related attributions and perceptions and parental support of the child were strong predictors of treatment outcome in this population. CONCLUSIONS: Therapeutic attention to children's sexual abuse-related attributions and to enhancing parental support may be important factors in optimizing treatment outcome in 8- to 14-year-old sexually abused children.

Probing the relationship between RNA-stimulated ATPase and helicase activities of HCV NS3 using 2'-O-methyl RNA substrates.

The hepatitis C virus (HCV) NS3 protein contains an amino terminal protease (NS3 aa. 1-180) and a carboxyl terminal RNA helicase (NS3 aa. 181-631). NS3 functions as a heterodimer of NS3 and NS4A (NS3/4A). NS3 helicase, a nucleic acid stimulated ATPase, can unwind RNA, DNA, and RNA:DNA duplexes, provided that at least one strand of the duplex contains a single-stranded 3' overhang (this strand of the duplex is referred to as the 3' strand). We have used 2'-O-methyl RNA (MeRNA) substrates to study the mechanism of NS3 helicase activity and to probe the relationship between its helicase and RNA-stimulated ATPase activities. NS3/4A did not unwind double-stranded (ds) MeRNA. NS3/4A unwinds hybrid RNA:MeRNA duplex containing MeRNA as the 5' strand but not hybrid duplex containing MeRNA as the 3' strand. The helicase activity of NS3/4A was 50% inhibited by 40 nM single-stranded (ss) RNA but only 35% inhibited by 320 nM ss MeRNA. Double-stranded RNA was 17 times as effective as double-stranded MeRNA in inhibiting NS3/4A helicase activity, while the apparent affinity of NS3/4A for ds MeRNA differed from ds RNA by only 2.4-fold. However ss MeRNA stimulated NS3/4A ATPase activity similar to ss RNA. These results indicate that the helicase mechanism involves 3' to 5' procession of the NS3 helicase along the 3' strand and only weak association of the enzyme with the displaced 5' strand. Further, our findings show that maximum stimulation of NS3 ATPase activity by ss nucleic acid is not directly related to procession of the helicase along the 3' strand.

Crystal structure of the RNA-dependent RNA polymerase from hepatitis C virus reveals a fully encircled active site.

Various classes of nucleotidyl polymerases with different transcriptional roles contain a conserved core structure. Less is known, however, about the distinguishing features of these enzymes, particularly those of the RNA-dependent RNA polymerase class. The 1. 9 A resolution crystal structure of hepatitis C virus (HCV) nonstructural protein 5B (NS5B) presented here provides the first complete and detailed view of an RNA-dependent RNA polymerase. While canonical polymerase features exist in the structure, NS5B adopts a unique shape due to extensive interactions between the fingers and thumb polymerase subdomains that serve to encircle the enzyme active site. Several insertions in the fingers subdomain account for intersubdomain linkages that include two extended loops and a pair of antiparallel alpha-helices. The HCV NS5B apoenzyme structure reported here can accommodate a template:primer duplex without global conformational changes, supporting the hypothesis that this structure is essentially preserved during the reaction pathway. This NS5B template:primer model also allows identification of a new structural motif involved in stabilizing the nascent base pair.

Volumetric bone density and geometry assessed by peripheral quantitative computed tomography in uremic patients on maintenance hemodialysis.

The aim of this study was to establish, by means of peripheral quantitative computed tomography (pQCT) at the distal radius, the existence of cortical and/or trabecular osteopenia, and to assess the integrity of bone geometry in uremic patients undergoing maintenance hemodialysis. Our results show a clearcut selective reduction in volumetric cortical density, more evident in women (p = -0.0001) than men (p = 0.030), which appears to be independent of age and menopausal status. Trabecular density was not significantly changed in either sex. Cortical density of the patients correlated inversely with age (p = 0.003), duration of dialysis (p = 0.002) and parathyroid hormone (PTH) levels (p = 0.03). Trabecular density correlated only with age. Normally, cortical density is age-dependent and its reduction is accompanied by compensatory geometry changes. Compared with control subjects, in our female patients both cortical area and cortical thickness were reduced (p = 0.02 and 0.008), while cross-sectional area did not change (p = 0.67). Conversely, in the males only cross-sectional area was reduced (p = 0.02). In conclusion, in uremic patients we observed a selective cortical osteopenia, more evident in the female sex, and a sex-specific pattern of geometry impairment, with resultant apparent increased bone fragility in the uremic women. We suggest that the prolonged PTH excess could be responsible, directly and/or interacting with estrogen deficiency.

Factors that mediate treatment outcome of sexually abused preschool children: six- and 12-month follow-up.

OBJECTIVE: The role of familial, demographic, developmental, and treatment-mediating factors on treatment outcome of sexually abused preschool children was evaluated 6 and 12 months after treatment. METHOD: Forty-three sexually abused preschool children and their parents who were evaluated shortly after disclosure of sexual abuse and then were provided with one of two treatment interventions were reevaluated at the completion of treatment and 6 and 12 months after treatment. Parents completed the Child Behavior Checklist, the Child Sexual Behavior Inventory, and the Weekly Behavior Report to measure a variety of emotional and behavioral symptoms in children. Parents also completed the Beck Depression Inventory, the Family Adaptability and Cohesion Evaluation Scales-III, the Parent Emotional Reaction Questionnaire, the Parental Support Questionnaire, and the Maternal Social Support Index. Children completed the Battelle Developmental Inventory and the Peabody Picture Vocabulary Test at pretreatment to assess developmental levels. RESULTS: Correlational and stepwise multiple regression analyses were conducted to analyze the role of the hypothesized mediating variables in predicting scores on outcome measures across the two treatment groups. While the Parent Emotional Reaction Questionnaire was the strongest familial predictor of treatment outcome at posttreatment, parental support became a stronger predictor of outcome at the 6- and 12-month follow-up points. Treatment group was the strongest overall predictor of outcome at posttreatment and at 12-month follow-up. Demographic and developmental factors did not strongly predict outcome. CONCLUSIONS: Findings indicate the strong impact of parental support on treatment outcome in sexually abused preschool children over the course of a 12-month follow-up and emphasize the importance of including parental interventions in treating sexually abused preschool children. They also support the superior effectiveness of cognitive-behavioral therapy over supportive counseling for this population.

A treatment study for sexually abused preschool children: outcome during a one-year follow-up.

OBJECTIVE: Treatment outcome in sexually abused preschool children was evaluated 6 and 12 months after treatment. METHOD: Forty-three sexually abused preschool children and their parents were evaluated 6 and 12 months after completion of either Cognitive-Behavioral Therapy for Sexually Abused Preschoolers (CBT-SAP) or nondirective supportive therapy (NST). Parents completed the Child Behavior Checklist, Child Sexual Behavior inventory, and Weekly Behavior Report to measure a variety of symptoms in their children. RESULTS: Repeated-measures analyses indicated that there were significant group by time interactions on several outcome measures from the beginning of the study to the end of the 12-month follow-up period, with the CBT-SAP group exhibiting significantly more improvement over time than the NST group. Clinical findings also indicated the superior effectiveness of CBT-SAP over NST in reducing sexually inappropriate behavior. CONCLUSIONS: Findings support the superior efficacy of CBT-SAP over NST in maintaining symptom reduction in the year after treatment completion. The importance of using cognitive-behavioral interventions for sexually inappropriate behaviors and including nonoffending parents in the treatment of sexually abused preschool children is discussed.

Factors that mediate treatment outcome of sexually abused preschool children.

OBJECTIVE: The role of demographic, developmental, and familial mediating factors on treatment outcome of sexually abused preschool children was evaluated. METHOD: Sixty-seven sexually abused preschool children and their parents were evaluated shortly after disclosure of sexual abuse and then were provided with one of two treatment interventions. At the completion of treatment, the parents and their children were reevaluated. Parents completed the Child Behavior Checklist, the Child Sexual Behavior Inventory, and the Weekly Behavior Report to measure a variety of emotional and behavioral symptoms in children. Parents also completed the Beck Depression Inventory, the Family Adaptability and Cohesion Evaluation Scale-III, the Parent Emotional Reaction Questionnaire, the Parental Support Questionnaire, and the Maternal Social Support Index. Children completed the Preschool Symptom Self-Report to assess self-reported affective symptoms and the Battelle Developmental Inventory and the Peabody Picture Vocabulary Test to assess developmental level. RESULTS: Correlational analyses were conducted to analyze the relationships between the hypothesized mediating variables and the outcome measures at posttreatment across the two treatment groups. Multiple regression analyses were also performed. Both parental depression and parental emotional distress correlated significantly with several of the child outcome measures. Battelle scores were significantly negatively correlated with several outcome measures. Multiple regression analyses demonstrated that the Parent Emotional Reaction Questionnaire remained a highly significant predictor of treatment outcome. CONCLUSIONS: The findings indicate a strong correlation between parental emotional distress related to the abuse and treatment outcome in sexually abused preschool children, independent of the type of treatment provided. The findings indicate the importance of addressing parental distress related to the abuse in providing effective treatment to sexually abused preschool children.

A treatment outcome study for sexually abused preschool children: initial findings.

OBJECTIVE: Treatment outcome for sexually abused preschool-age children and their parents was assessed, comparing the effectiveness of a cognitive-behavioral intervention to nondirective supportive treatment. METHOD: Sixty-seven sexually abused preschool children and their parents were randomly assigned to either (1) cognitive-behavioral therapy adapted for sexually abused preschool children (CBT-SAP) or (2) nondirective supportive therapy (NST). Treatment consisted of 12 individual sessions for both the child and parent, monitored for integrity with the therapeutic model through intensive training and supervision, use of treatment manuals, and rating of audiotaped sessions. Parents completed the Child Behavior Checklist, the Child Sexual Behavior Inventory, and the Weekly Behavior Report to measure a variety of emotional and behavioral symptoms. RESULTS: Within-group comparison of pretreatment and posttreatment outcome measures demonstrated that while the NST group did not change significantly with regard to symptomatology, the CBT-SAP group had highly significant symptomatic improvement on most outcome measures. Repeated-measures analyses of variance demonstrated group x time interactions on some variables as well. Clinical findings also supported the effectiveness of the CBT-SAP intervention over NST. CONCLUSIONS: Findings provide strong preliminary evidence for the effectiveness of a specific cognitive-behavioral treatment model for sexually abused preschool children and their parents.

[A case of HELLP syndrome with dramatic course successfully treated with early plasmapheresis]. / Un caso di Hellp syndrome a decorso drammatico risolto con plasmaferesi precoce.

A case of Hellp syndrome occurred in postpartum of a pregnancy elapsed without signs of preeclampsia is described. The evolution was particularly dramatic. Early plasmapheresis was the key treatment for a complete recovery in order to avoid Multiple Organ Dysfunction System (MODS). Emphasis on a multidisciplinary approach between Gynecologist, Anesthetist, Nephrologist and Hematologist is pointed out.

The relationship between preabuse factors and psychological symptomatology in sexually abused girls.

This study investigated the relationship between preabuse factors and psychological symptomatology in sexually abused girls. Ninety-four sexually abused girls, 89 clinical controls, and 75 normal controls comprised the subject population. All subjects were ages 6-12. Preabuse information was obtained with the Developmental, Psychiatric, and Medical History (DPM). Symptom measures included the Children's Depression Inventory (CDI), State-Trait Anxiety Inventory for Children (STAIC), Piers-Harris Children's Self-Concept Scale, and the Child Behavior Checklist (CBCL parent version). Results indicated that the sexually abused and clinical control groups had significantly more prior developmental and psychiatric problems and significantly more past stressors on the DPM than the normal control group. In addition, in examining the sexually abused group only, prior developmental and psychiatric problems were clearly associated with increased behavioral and emotional problems (CBCL), self-reported depressive symptoms (CDI), and lower self-esteem (Piers-Harris). Parallel results were found in the clinical control group, although correlations were higher in the sexual abuse group. Findings are interpreted to support the notion that there are a multitude of variables that may affect the psychological adjustment of sexually abused children, including preabuse and post-abuse factors and the trauma of the abusive experience itself.

Isolation and purification of a biologically active human platelet-derived growth factor BB expressed in Escherichia coli.

Human platelet-derived growth factor (PDGF) was expressed in Escherichia coli from a high-level cytoplasmic expression vector. A cDNA fragment encoding the mature form of the human PDGF B chain (hPDGF-B) was cloned into a plasmid under transcriptional control of the inducible E. coli Tac promoter. Expression of hPDGF-B from the final construct, pTacBIq, is regulated by the lactose repressor (LacIq). Upon induction, a polypeptide of approximately 14 kDa that had the same molecular mass and immunoreactivity as authentic hPDGF-B was produced. The production of recombinant hPDGF-B was significantly increased in an E. coli strain (CAG629) defective in expression of the lon protease. Expression of hPDGF-B in the CAG629 strain accounted for approximately 1% of total cell protein. In this system, hPDGF-B is expressed as an insoluble, intracellular protein and can readily be obtained in a partially purified form after differential centrifugation. Amino acid sequence determination of the purified protein has verified that the amino-terminal portion of the recombinant PDGF is correct. After renaturation into dimers, the purified recombinant hPDGF is fully functional in assays for receptor binding and mitogenesis.

Integration of a token economy into a child and adolescent psychiatry training clinic.

We developed a token economy pilot program in which reinforcers were provided by a university outpatient child and adolescent psychiatry clinic to address two problems common to psychiatry training programs: 1) psychiatric residents have insufficient opportunity to learn to use behavior modification techniques with outpatients, and 2) many patients and their parents seen in training clinics are poorly motivated and noncompliant with treatment, which leads to psychiatry resident discouragement and frustration. The rationale for the program is presented from the perspective of both the resident and the patient. The implementation of the program with 25 cases is described, including potential and actual difficulties. One case treated by a psychiatry resident is presented in more detail.

A new technique for transscleral fixation of a posterior chamber intraocular lens in the absence of capsular support during penetrating keratoplasty.

In the setting of penetrating keratoplasty for the rehabilitation of aphakic or pseudophakic bullous keratopathy, a posterior chamber intraocular lens is frequently implanted in the absence of capsular support. Some surgeons have advocated transscleral fixation over iris fixation of the intraocular lens. Problems faced during such a procedure, however, include the obstructed approach of the suture needle behind the iris, and the exposed or eroded knot of the polypropylene suture. To circumvent both problems, we propose an ab externo technique that takes advantage of the work of Duffey et al and avoids the use of partial thickness scleral flaps.

Purification and characterization of a cyclic GMP-stimulated cyclic nucleotide phosphodiesterase from the cytosol of human platelets.

A cyclic GMP-stimulated cyclic nucleotide phosphodiesterase was purified to near homogeneity from the 150,000 g supernatant fraction of human platelets by a combination of DEAE-cellulose chromatography and cyclic GMP affinity chromatography. Overall purification was about 7400-fold with a 10% to 15% recovery of activity. On NaDodSO4-containing polyacrylamide gels, the purified enzyme migrates as a single band Mr = 105,000. Phosphodiesterase activity co-migrates with the protein band on native polyacrylamide gels. Both Mg2+ and Mn2+ support the activity of this phosphodiesterase. The enzyme hydrolyzes both cyclic AMP and cyclic GMP with similar maximal rates. The hydrolysis of both nucleotides exhibits positive homotropic cooperativity with S0.5 values of 50 +/- 12 microM for cyclic AMP and 35 +/- 15 microM for cyclic GMP and Hill coefficients of 1.2 to 1.5 for both nucleotides. Low levels of cyclic GMP stimulate the rate of cyclic AMP hydrolysis from 3- to 10-fold. The activity of this phosphodiesterase is not stimulated by the calcium binding protein, calmodulin. The cyclic GMP stimulation of cyclic AMP hydrolysis by this phosphodiesterase may provide a possible regulatory link between the metabolism of these two nucleotides in platelets.

Unilateral graft rejection after bilateral antigenically identical corneal transplantation.

A unique case of unilateral graft rejection after bilateral antigenically identical corneal transplantation is described. The local risk factors (corneal vascularity and elevated intraocular pressure) were present to a greater extent in the nonrejected eye. The influence of other factors on the corneal microenvironment and their relationship to graft/host interactions is discussed.

cAMP-mediated phosphorylation of the low-Km cAMP phosphodiesterase markedly stimulates its catalytic activity.

Treatment of intact human platelets with the adenylate cyclase agonist forskolin (100 microM) resulted in an increase in cAMP phosphodiesterase activity in freeze-thaw lysates. When the low-Km (high affinity), cGMP-inhibited cAMP phosphodiesterase was isolated from such lysates by blue dextran-Sepharose chromatography, the specific activity of the enzyme was increased an average of 11-fold over similarly processed control platelets. The increase in the low-Km, cGMP-inhibited cAMP phosphodiesterase activity was inhibited when platelets were incubated with the protein kinase inhibitor H-8 prior to treatment with forskolin, suggesting that the stimulation of cAMP phosphodiesterase activity involved a cAMP-dependent phosphorylation. When intact platelets that had been prelabeled with 32Pi were treated with forskolin and the low-Km, cGMP-inhibited phosphodiesterase was isolated by blue dextran-Sepharose chromatography, a protein of 110,000 kDa was phosphorylated. By using a monospecific antiserum to the purified phosphodiesterase, this protein was shown to be the low-Km, cGMP-inhibited cAMP phosphodiesterase by electrophoretic transfer blot (Western blot) analysis and by immunoprecipitation. The stable prostacyclin analog iloprost also stimulated the low-Km cAMP phosphodiesterase activity about 2-fold and caused phosphorylation of the enzyme. These results suggest that phosphorylation of the low-Km, cGMP-inhibited phosphodiesterase may be an important regulatory mechanism for this enzyme in platelets.

Psychological symptoms in sexually abused girls.

This study examined psychological symptoms exhibited by children who had recently been sexually abused. Twenty-four girls aged 6 to 12 years old were evaluated within six months of being abused using a variety of standardized child psychiatric instruments. Results showed a marked discrepancy between child and parent reports of symptoms. The abused children did not exhibit significant depressive, anxiety, or low self-esteem symptoms by self-report; however, their parents rated them as having significantly more behavioral problems than a normative sample but as somewhat less pathological than a clinical sample. The implications of these findings in relation to our current understanding of the psychological problems manifested by sexually abused children and for future research are discussed.