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Biomedical subjects

J Bridge

Publications and source records attributed to J Bridge.

At least 19 recordsLinked to original sources
PubMed2001

The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25.

Alveolar soft part sarcoma (ASPS) is an unusual tumor with highly characteristic histopathology and ultrastructure, controversial histogenesis, and enigmatic clinical behavior. Recent cytogenetic studies have identified a recurrent der(17) due to a non-reciprocal t(X;17)(p11.2;q25) in this sarcoma. To define the interval containing the Xp11.2 break, we first performed FISH on ASPS cases using YAC probes for OATL1 (Xp11.23) and OATL2 (Xp11.21), and cosmid probes from the intervening genomic region. This localized the breakpoint to a 160 kb interval. The prime candidate within this previously fully sequenced region was TFE3, a transcription factor gene known to be fused to translocation partners on 1 and X in some papillary renal cell carcinomas. Southern blotting using a TFE3 genomic probe identified non-germline bands in several ASPS cases, consistent with rearrangement and possible fusion of TFE3 with a gene on 17q25. Amplification of the 5' portion of cDNAs containing the 3' portion of TFE3 in two different ASPS cases identified a novel sequence, designated ASPL, fused in-frame to TFE3 exon 4 (type 1 fusion) or exon 3 (type 2 fusion). Reverse transcriptase PCR using a forward primer from ASPL and a TFE3 exon 4 reverse primer detected an ASPL-TFE3 fusion transcript in all ASPS cases (12/12: 9 type 1, 3 type 2), establishing the utility of this assay in the diagnosis of ASPS. Using appropriate primers, the reciprocal fusion transcript, TFE3-ASPL, was detected in only one of 12 cases, consistent with the non-reciprocal nature of the translocation in most cases, and supporting ASPL-TFE3 as its oncogenically significant fusion product. ASPL maps to chromosome 17, is ubiquitously expressed, and matches numerous ESTs (Unigene cluster Hs.84128) but no named genes. The ASPL cDNA open reading frame encodes a predicted protein of 476 amino acids that contains within its carboxy-terminal portion of a UBX-like domain that shows significant similarity to predicted proteins of unknown function in several model organisms. The ASPL-TFE3 fusion replaces the N-terminal portion of TFE3 by the fused ASPL sequences, while retaining the TFE3 DNA-binding domain, implicating transcriptional deregulation in the pathogenesis of this tumor, consistent with the biology of several other translocation-associated sarcomas. Oncogene (2001) 20, 48 - 57.

Adolescent↗
PubMed2001

Subsyndromal depression in adolescents after a brief psychotherapy trial: course and outcome.

INTRODUCTION: Subsyndromal depression has been associated with an increased risk of the development of major depressive disorder (MDD). Since treatment trials of adolescent MDD often result in subsyndromal depression as the outcome, the long-term course of these youth would be useful to understand. METHODS: 107 adolescents with MDD participated in a clinical psychotherapy trial, of whom 99 were followed up for two years after acute treatment. Those with subsyndromal depression (2-3 symptoms) at the end of acute treatment were compared to those who were well (< or =1 symptom) and those who were still depressed (> or =4 symptoms) on presentation at intake, the end of treatment, and over the two-year follow-up. RESULTS: Of the 99 youth, at the end of acute treatment 26 were well, 18 were subsyndromal, and 55 were still depressed. A substantial proportion of the subsyndromally depressed youth were functionally impaired (38%), and showed a protracted time to recovery. The risk of recurrence was similar to those who were without depression at the end of acute treatment (46% vs. 44%). Recurrence was predicted by depressive symptom severity and family difficulties at the end of acute treatment. LIMITATIONS: A large proportion of the subsyndromal groups received open treatment that may have altered their course. Also, this was a referred sample, rather than an epidemiological one. CONCLUSIONS: In clinical samples treated with psychotherapy, subsyndromal depression poses a significant risk for functional impairment and protracted recovery. Depressive recurrence may be prevented by targeting reduction of symptom severity and of family difficulties.

Activities of Daily Living↗
PubMed2001

Adult outcomes of pediatric recurrent abdominal pain: do they just grow out of it?

OBJECTIVE: To determine whether medically unexplained recurrent abdominal pain (RAP) in childhood predicts abdominal pain, irritable bowel syndrome (IBS), other somatic complaints, and psychiatric symptoms and disorders in young adulthood. METHODS: A sample of 28 young adults evaluated for RAP between the ages of 6 and 17 years were compared with 28 individually matched former childhood participants in a study of tonsillectomy and adenoidectomy. RAP caseness was established by structured retrospective chart review requiring agreement by 2 independent reviewers. Standardized assessments of abdominal pain, IBS, other somatic symptoms, psychopathology, perceived health, and history of maltreatment were performed an average of 11.1 years after the index visit. RESULTS: Former RAP patients were significantly more likely than controls to endorse anxiety symptoms and disorders, hypochondriacal beliefs, greater perceived susceptibility to physical impairment, poorer social functioning, current treatment with psychoactive medication, and generalized anxiety in first degree relatives. There were trends suggesting associations between childhood RAP and lifetime psychiatric disorder, depression, migraine, and family history of depression, but group differences on abdominal pain, IBS, other somatic symptoms, and history of maltreatment were not statistically significant. CONCLUSIONS: There is a strong and relatively specific association between childhood RAP and anxiety in young adulthood. Affected children may be at special risk to perceive physical symptoms as threatening, and should be evaluated for psychiatric disorder on initial presentation.

Abdominal Pain↗
PubMed2001

Predictors of parent-rated credibility in a clinical psychotherapy trial for adolescent depression.

The authors have reported that adolescents with major depressive disorder had a higher remission rate with cognitive-behavioral therapy (CBT) than with systemic behavioral family therapy (SBFT) or nondirective supportive therapy (NST). Parent-rated treatment credibility deteriorated from baseline to end of treatment if patients were treated with SBFT or NST, compared with CBT. The present study evaluated the following variables as predictors of change in parent- rated credibility over time across the three treatment cells: severity of child's and parents' depression at baseline; parent-rated family climate at baseline; clinician age, gender, and years of clinical experience; and change in severity of child's depression and in family climate. The greater the baseline depression of children treated with CBT and NST, but not SBFT, the more favorable the change in parent-rated credibility at the end of treatment. Findings suggest that any improvement (for CBT) or a supportive therapeutic contact (for NST) may appeal to parents of severely depressed children.

Adolescent↗
PubMed2000

Frequent loss of 9p21 (p16(INK4A)) and other genomic imbalances in human malignant fibrous histiocytoma.

To search for new recurrent genetic aberrations in malignant fibrous histiocytoma (MFH), a combination of conventional cytogenetic, comparative genomic hybridization (CGH), and Southern blot analyses was applied to a series of 34 tumors. Cytogenetic analysis revealed the presence of multiple structural and numerical aberrations, including marker chromosomes, telomeric associations, double minutes, and ring chromosomes. The most frequent genomic imbalances in this series of neoplasms as detected by CGH were gains of 1q21-q22 (69%), 17q23-qter (41%), and 20q (66%), and losses of 9p21-pter (55%), 10q (48%), 11q23-qter (55%), and 13q10-q31 (55%). Southern blot analyses with p16(INK4A) (CDKN2A; 9p21) and RB1 (13q14) probes provided clear indications for frequent deletions of these tumor suppressor genes, and as such, substantiated the CGH results. Additionally, examination of the TP53 and MDM2 genes showed frequent loss and amplification, respectively. These data indicate that genes involved in the RB1- and TP53-associated cell cycle regulatory pathways may play prominent roles in the development of human MFH.

Blotting, Southern↗
PubMed2000

Clinical outcome after short-term psychotherapy for adolescents with major depressive disorder.

BACKGROUND: Cognitive behavioral therapy has been shown to be more efficacious than alternative psychosocial interventions for the acute treatment of adolescents with major depressive disorder. However, the long-term impact of brief psychosocial interventions on the course of adolescent depression is not well established. METHODS: One hundred seven adolescents with major depressive disorder randomly assigned to 12 to 16 weeks of cognitive behavioral therapy, systemic behavioral family therapy, or nondirective supportive therapy were evaluated for 2 years after the psychotherapy trial to document the subsequent course and predictors of major depressive disorder. RESULTS: There were no long-term differential effects of the 3 psychotherapies. Most participants (80%) recovered (median time, 8.2 months from baseline), and 30% had a recurrence (median time, 4.2 months from recovery). Twenty-one percent were depressed during at least 80% of the follow-up period. Severity of depression (at baseline) and presence of self-reported parent-child conflict (at baseline and during the follow-up period) predicted lack of recovery, chronicity, and recurrence. Despite the similarity to clinically referred patients at baseline, patients recruited via advertisement were less likely to experience a recurrence. CONCLUSIONS: There were no significant differences in long-term outcome among cognitive behavioral therapy, systematic behavioral family therapy, and nondirective supportive therapy. While most participants in this study eventually recovered, those with severe depression and self-perceived parent-child conflict are at greater risk for chronic depression and recurrences.

Adolescent↗
PubMed2000

Screen for Child Anxiety-Related Emotional Disorders (SCARED): convergent and divergent validity.

The purpose of this study was to examine the Screen for Child Anxiety-Related Emotional Disorders' (SCARED) divergent and convergent validity and its ability to identify anxious children. The SCARED, the Child Behaviour Checklist (CBCL), and the State-Trait Anxiety Inventory for Children (STAIC) were administered to children, adolescents (n = 295), and their parents attending an outpatient mood and anxiety disorders clinic. DSM-IIIR/IV diagnoses were made using a semistructured interview (n = 130) or a symptom checklist (n = 165). The Multi-Trait Multi-Method Matrix was used to assess construct validity, and Receiver Operating Curve analysis was used to assess the sensitivity and specificity of the SCARED, CBCL, and STAIC. The SCARED correlated significantly better with the CBCL's internalizing factors than with the externalizing factors. In addition, parent and child forms of the SCARED correlated significantly with the trait and state subscales of the STAIC. Children with an anxiety disorder scored significantly higher on the SCARED than children with depression only or disruptive disorders only (P < 0.05), thus demonstrating the discriminant validity of the SCARED. The SCARED is a reliable and valid screening tool for clinically referred children and adolescents with anxiety disorders.

Adolescent↗
PubMed2000

Mutation analysis of P73 and TP53 in Merkel cell carcinoma.

The p73 gene has been mapped to 1p36.33, a region which is frequently deleted in a wide variety of neoplasms including tumours of neuroectodermal origin. The p73 protein shows structural and functional homology to p53. For these reasons, p73 was considered as a positional and functional candidate tumour suppressor gene. Thus far, mutation analysis has provided no evidence for involvement of p73 in oligodendrogliomas, lung carcinoma, oesophageal carcinoma, prostatic carcinoma and hepatocellular carcinoma. In neuroblastoma, two mutations have been observed in a series of 140 tumours. In view of the occurrence of 1p deletions in Merkel cell carcinoma (MCC) and the location of p73 we decided to search for mutations in the p73 gene in five MCC cell lines and ten MCC tumours to test potential tumour suppressor function for this gene in MCC. In view of the possible complementary functions of p73 and TP53 we also examined the status of the TP53 gene. Sequence analysis of the entire coding region of the p73 gene revealed previously reported polymorphisms in four MCCs. In one MCC tumour, a mis-sense mutation located in the NH2-terminal transactivation region of the p73 gene was found. These results show that p73, analogous to neuroblastoma, is infrequently mutated in MCC. This is also the first report in which the role of TP53 in MCC has been investigated by sequencing the entire coding region of TP53. TP53 mis-sense mutations and one non-sense mutation were detected in three of 15 examined MCCs, suggesting that TP53 mutations may play a role in the pathogenesis or progression of a subset of MCCs. Moreover, typical UVB induced C to T mutations were found in one MCC cell line thus providing further evidence for sun-exposure in the aetiology of this rare skin cancer.

Base Sequence↗
PubMed2000

Psychosis in a pediatric mood and anxiety disorders clinic: phenomenology and correlates.

OBJECTIVES: To examine the demographics and phenomenology of psychosis in a sample of children and adolescents referred to a mood and anxiety disorders clinic. METHOD: Patients (N = 2,031) were assessed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode version and classified as definite, probable, or nonpsychotic. Clinical and demographic characteristics of the groups were compared,and symptoms of psychosis were analyzed using factor analysis. RESULTS: Definite psychotic symptoms were seen in approximately 90 (4.5%) patients: 80% of these reported hallucinations (mainly auditory), 22% delusions, and 3.3% thought disorder. Of the patients with definite psychotic symptoms, 24% had bipolar disorder, 41% had major depression, 21% had subsyndromal depression, and 14% had schizophrenia spectrum disorders (schizophrenia and schizoaffective disorders). Factor analysis of the definite psychotic symptoms yielded 4 factors: hallucinations, thought disorder, delusions, and manic thought disorder. Psychotic patients had a higher frequency of comorbid disorders and suicidal ideation than nonpsychotic patients. CONCLUSIONS: Outpatient youngsters with mood disorders frequently present with psychotic symptoms, in particular auditory hallucinations. These patients commonly have comorbid psychiatric disorders and suicidal ideation.

Adolescent↗
PubMed2000

Compliance with recommendations to remove firearms in families participating in a clinical trial for adolescent depression.

OBJECTIVE: To assess the rate and correlates of compliance with clinicians' recommendations to remove firearms from the homes of depressed adolescents participating in a clinical trial. METHOD: The parents of 106 adolescents with major depression who participated in a randomized psychotherapy clinical trial were asked systematically about firearms in the home. Those who answered affirmatively were given information about the suicide risk conveyed by guns in the home and urged to remove them. The rates of gun removal and acquisition were assessed at the end of the treatment and over the subsequent 2-year naturalistic follow-up. RESULTS: Of those who had guns at intake, 26.9% reported removing them by the end of the acute trial. Retention was associated with urban origin, marital dissatisfaction, and paternal psychopathology. Of those who did not have guns at intake, 17.1% reported acquiring them over 2-year follow-up. Living in a 2-parent household and marital dissatisfaction were associated with gun acquisition. CONCLUSIONS: Families of depressed adolescents may frequently be noncompliant with recommendations to remove guns from the home despite compliance with other aspects of treatment. More efficacious interventions to reduce access to guns in the homes of at-risk youths are needed.

Adolescent↗
PubMed2000

Anxiety disorders in suicidal youth.

OBJECTIVE: To test the hypothesis that anxiety disorders are associated with suicidal ideation and suicide attempts in a child and adolescent sample referred to a clinic. METHOD: The sample comprised 1979 patients aged 5 to 19 years who were assessed using the Schedule for Affective Disorders and Schizophrenia for School Aged Children--Present Episode (K-SADS-P) at an outpatient mood and anxiety disorders clinic. Subjects were stratified by age and categorized into mutually exclusive groups as being nonsuicidal (n = 817), having suicidal ideation (n = 768), or having attempted suicide (n = 394) in the current episode. Psychiatric diagnoses based on DSM-IV criteria were compared to determine if anxiety disorders were a risk factor for suicidal ideation and suicide attempts. Logistic regression was used to control for significant demographic characteristics and comorbid disorders. RESULTS: After stratifying by age, we found no differences across the 3 groups (ideators, attempters, and nonsuicidal youth) in rates of an anxiety disorder in general or in specific rates of panic disorder, agoraphobia, social phobia, simple phobia, and obsessive-compulsive disorder. Two salient findings involving anxiety disorders were noted with regression analysis. In younger children (age < or = 15 years), attempters had a significantly lower prevalence of separation anxiety disorder (SAD), compared with ideators (OR = 0.30; 95%CI, 0.11 to 0.80; P = 0.006) and nonsuicidal youngsters (OR = 0.14; 95%CI, 0.05 to 0.39; P < 0.0001). In older children (age > 15 years), generalized anxiety disorder (GAD) was more prevalent in ideators (OR = 1.65; 95%CI, 1.03 to 2.66; P = 0.03) than in nonsuicidal patients. CONCLUSIONS: Based on this clinical sample, the relation between pediatric anxiety disorder and suicidal ideation and suicide attempts is not straightforward. However, further studies in nonreferred samples are warranted.

Adolescent↗
PubMed2000

Cognitive and family therapies for adolescent depression: treatment specificity, mediation, and moderation.

The specificity of cognitive and family therapies, and potential treatment mediators and moderators, was examined in a randomized clinical trial for adolescent depression. After acute treatment, cognitive-behavioral therapy (CBT) exerted specific effects on cognitive distortions relative to either systemic-behavioral family therapy (SBFT) or nondirective supportive therapy (NST). At 2-year follow-up, SBFT was found to impact family conflict and parent-child relationship problems more than CBT; NST and CBT tended to show a greater reduction in anxiety symptoms than SBFT. Nonspecific therapist variables qualified few outcome analyses. No measures of cognitive distortion or family dysfunction mediated or moderated treatment outcome. As in adult studies, relatively few areas of treatment specificity or mediation were identified. The implications of these findings for clinical treatment and research in adolescent depression are discussed.

Adolescent↗
PubMed1999

Use of selective serotonin reuptake inhibitors for the treatment of childhood panic disorder: a pilot study.

This preliminary study examines the effectiveness and safety of selective serotonin reuptake inhibitors (SSRIs) for the treatment of panic disorder in children and adolescents. In a prospective open label study, 12 children and adolescents with panic disorder were treated with SSRIs, and if necessary, with benzodiazepines, for a period of 6-8 weeks and were followed for approximately 6 months. During the trial, clinician-based and self-report rating scales for anxiety and depression, functioning, and side effects, were administered. Using the Clinical Global Impression Scale (CGIS) 75% of patients showed much to very much improvement with SSRIs without experiencing significant side effects. After controlling for changes in depressive symptoms, self-report and clinician-based anxiety scales also showed significant improvement. At the end of the trial, 67% of patients no longer fulfilled criteria for panic disorder and 4 patients remained with significant residual symptoms. In conclusion, SSRIs appear to be a safe and promising for the treatment of children and adolescents with panic disorder, however, randomized controlled trials evaluating the effects of SSRIs and other interventions (e.g., cognitive therapy) for treating panic disorder in children and adolescents are warranted. It appears that until the SSRIs begin to exert their effects, a benzodiazepine adjunct treatment might be helpful for patients with severe panic disorder.

Adolescent↗
PubMed1999

A clinical trial for adolescent depression: predictors of additional treatment in the acute and follow-up phases of the trial.

OBJECTIVE: To examine the predictors of additional service use among participants in a clinical trial for depression. METHOD: 107 adolescents with DSM-III-R depression were randomly assigned to receive either cognitive-behavioral therapy, systemic behavioral family therapy, or nondirective supportive therapy for 12 to 16 weeks of acute treatment and followed up periodically for 24 months after the termination of acute treatment. RESULTS: More than half (53.3%) of the 107 randomized adolescents received additional treatment beyond that provided in the clinical trial, with a median time to additional treatment from intake of 7.2 months. The rates and times to additional treatment were similar in the 3 treatment groups, despite the superior efficacy of cognitive-behavioral therapy in the acute phase. The severity of the index depressive episode and comorbid dysthymia were a predictor of additional treatment in the acute phase, whereas in the follow-up period the severity of depressive symptomatology, the presence of disruptive disorders, and family problems predicted additional treatment. CONCLUSIONS: Subsequent clinical trials for early-onset depression must focus on the entire depressive episode, rather than just the acute phase, to prevent depressive relapse. In addition, attendant family difficulties and comorbid behavioral problems must be addressed.

Acute Disease↗
PubMed1999

Suicide in adolescents with disruptive disorders.

OBJECTIVE: To determine the psychiatric risk factors for suicide in adolescents with disruptive disorders. METHOD: Fifty-nine adolescent suicide completers and 18 community controls, both having a probable or definite current DSM-III diagnosis of disruptive disorders, were compared. RESULTS: Adolescents with disruptive disorders who committed suicide had higher rates of current substance abuse, past suicide attempt, family history of substance abuse, and family history of mood disorder than disruptive community controls. CONCLUSIONS: Disruptive adolescents appear to be at risk for completed suicide when comorbid substance abuse and past history of suicide attempt are present. The risk increases if the adolescents have a past history of physical abuse and if they have parents with substance abuse and mood disorders. Clinicians should be aware of these risk factors and implement active interventions to prevent suicide. Treatment should focus on treating not only the adolescents, but also their family members. The findings of this study also highlight the need for future research in the prevention of suicide in adolescents with disruptive disorders and comorbid substance abuse.

Adolescent↗
PubMed1999

Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a replication study.

OBJECTIVE: To replicate and extend work on the psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED), a child and parent self-report instrument used to screen for children with anxiety disorders. METHOD: The 41-item version of the SCARED was administered to a new sample of 190 outpatient children and adolescents and 166 parents. The internal consistency, discriminant, and convergent validity were assessed. In addition, using discriminant function analysis, a briefer version of the SCARED was developed. RESULTS: Using item analyses and factor analyses on the 41-item version, 5 factors were obtained: panic/somatic, generalized anxiety, separation anxiety, social phobia, and school phobia. In general, the total score and each of the 5 factors for both the child and parent SCARED demonstrated good internal consistency and discriminant validity (both between anxiety and depressive and disruptive disorders and within anxiety disorders). A reduced version of the SCARED yielded 5 items and showed similar psychometrics to the full SCARED. CONCLUSIONS: In a new sample, the authors replicated their initial psychometric findings that the SCARED is a reliable and valid instrument to screen for childhood anxiety disorders in clinical settings. Furthermore, pending future research, the 5-item SCARED appears to be a promising brief screening inventory for anxiety disorders in epidemiological studies.

Adolescent↗
PubMed1999

Outcome at 6 months for 50 adolescents with major depression treated in a health maintenance organization.

OBJECTIVE: To examine the short-term outcome of adolescents with major depressive disorder treated in a health maintenance organization (HMO) setting. METHOD: Fifty consecutive adolescents meeting DSM-IV criteria for major depressive disorder at intake to an HMO clinic completed a Beck Depression Inventory (BDI), Columbia Impairment Scale, and Youth Self-Report (YSR), and a parent completed a Child Behavior Checklist at intake and 2, 4, and 6 months later. RESULTS: Thirty-three percent, 40.6%, and 33% of reporting subjects showed improved mood (defined as BDI score < 9), with 78%, 64%, and 72% reporting (defined as completing a BDI) at 2, 4, and 6 months, respectively. Initial level of impairment correlated with BDI score at 2 months (p = .02) and 4 months (p = .01). Attention problems at intake as measured by the YSR correlated with BDI score at 2 months (p = .002) and 6 months (p = .003). CONCLUSIONS: A minority of adolescents treated with limited, nonspecific psychotherapy and selective serotonin reuptake inhibitors have a BDI score of less than 9 at 2, 4, or 6 months. Self-report of attention problems at intake correlates with ongoing depressive symptomatology.

Adolescent↗