- Psychology, Child and Adolescent
- Medical Illness and Cognitive Functioning
- Pediatric Traumatic Brain Injury
Clinical Professor, Psychiatry and Behavioral Sciences - Child and Adolescent Psychiatry
Co-Director, Child Psychology Practicum Program, Division of Child and Adolescent Psychiatry, Stanford University School of Medicine (2014 - Present)
Director, Child Psychology, Division of Child and Adolescent Psychiatry, Stanford University School of Medicine (2005 - 2012)
Director, Child Psychology Postdoctoral Training Program, Division of Child and Adolescent Psychiatry, Stanford University School of Medicine (1998 - Present)
Director, Outpatient Services, Division of Child and Adolescent Psychiatry, Stanford University School of Medicine (1998 - 2012)
Honors & Awards
Faculty Fellows Program, Office of Diversity and Leadership, Stanford University School of Medicine (2006)
Katherine McCormick Fund Travel Award, Stanford University School of Medicine (2004)
Boards, Advisory Committees, Professional Organizations
Member, Appointment and Promotions Committee, Clinical Assistant Professors, Stanford University School of Medicine (2015 - Present)
Member, Postdoctoral Membership and Review Committee, Association of Psychology Postdoctoral and Internship Centers (APPIC) (2014 - Present)
Campus Training Representative, Federal Education Advocacy Coordinators Network, American Psychological Association (APA) (2012 - Present)
Member, Clinical Executive Committee-Child, Department of Psychiatry, Stanford University School of Medicine (2012 - Present)
Member, Well Being Committee, Packard Children’s Hospital at Stanford (2011 - Present)
Member, Education Leadership and Integration Committee, Department of Psychiatry, Stanford University School of Medicine (2011 - Present)
Member, Academic Promotions - Clinician Educator Committee, Department of Psychiatry, Stanford University School of Medicine (2011 - 2015)
Member, National Academy of Neuropsychology (2002 - Present)
Fellowship:Stanford University School of Medicine Registrar (1997) CA
BA, Pomona College, Psychology (1988)
University of Cincinnati (1995) OH
Internship:VA Medical Center (1994) CA
PhD, University of Cincinnati, Clinical Psychology (1995)
Current Research and Scholarly Interests
Dr. Williams work focuses primarily on cognitive and emotional recovery of children who have been medically compromised. With improved medical treatment and increased survival rates comes the need to better understand the challenges that patients face following a life threatening illness or injury. Advances in medical technology have opened the door to a better understanding of cognitive development and the recovery or deterioration process over time. Currently, Dr. Williams is examining the neuropsychological impact of treatment for children who have undergone a bone marrow transplant (BMT). The existence of cognitive deficits in this population intellectual and academic functioning, memory impairment, visual motor difficulties, problems with attention, concentration and executive functioning - has been in question over the years with research supporting both perspectives. Clinical experience and patient report, however, support the hypothesis that cognitive difficulties exist. New technologies such as imaging, used in concert with established neuropsychological measurement, offer great promise in expanding our understanding of the impact of these treatments and ultimately, improving outcome. Dr. Williams is conducting a NIH funded study examining neuropsychological functioning, imaging and genetic data. Additionally, Dr. Williams has studied children with traumatic brain injuries and continues to see these children in her clinical practice.
Long Term Effects On Recipients of Hematopoietic Stem Cell Transplantation
This project allows for the systematic collection and analysis of long-term follow-up clinical parameters in children who have received a stem cell transplant. The data collected will assist in determining appropriate intervention and treatment plans for patients enrolled on this study. In addition, future patients may benefit by having the ability to anticipate problems and develop methods of prevention or early intervention.
- Impact of Pivotal Response Training Group Therapy on Stress and Empowerment in Parents of Children With Autism JOURNAL OF POSITIVE BEHAVIOR INTERVENTIONS 2013; 15 (2): 71-78
Brief Cognitive-Behavioral Intervention for Maternal Depression and Trauma in the Neonatal Intensive Care Unit: A Pilot Study
JOURNAL OF TRAUMATIC STRESS
2011; 24 (2): 230-234
Parents of hospitalized premature infants are at risk for developing psychological symptoms. This randomized controlled pilot study examined the effectiveness of a brief cognitive-behavioral intervention in reducing traumatic and depressive symptoms in mothers 1 month after their infant's discharge from the hospital. Fifty-six mothers were randomly assigned to the intervention or control group. Results showed that mothers experienced high levels of symptoms initially and at follow-up. At follow-up, there was a trend for mothers in the intervention group to report lower levels of depression (p = .06; Cohen's f = .318), but levels of traumatic symptoms were similar for both groups. Brief psychological interventions may reduce depressive symptoms in this population. Estimates of the effect sizes can be used to inform future intervention studies.
View details for DOI 10.1002/jts.20626
View details for Web of Science ID 000289528300014
View details for PubMedID 21438016
EXECUTIVE FUNCTIONING IN PEDIATRIC STEM CELL TRANSPLANTATION UTILIZING FMRI
Annual Meeting of the American-Society-for-Blood-and-Marrow-Transplantation(BMT) Tandem
ELSEVIER SCIENCE INC. 2011: S243–S243
View details for Web of Science ID 000287350500242
Pivotal Response Group Treatment Program for Parents of Children with Autism
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
2011; 41 (1): 92-101
The number of children diagnosed with autism spectrum disorders is increasing, necessitating the development of efficient treatment models. Research has demonstrated that parent-delivered behavioral interventions are a viable treatment model; however, little research has focused on teaching parents in groups. The aim of this study was to demonstrate that parents can learn Pivotal Response Training (PRT) in group therapy, resulting in correlated gains in children's language. Baseline and post-treatment data were obtained and examined for changes in (a) parent fidelity of PRT implementation, and (b) child functional verbal utterances. Significant differences were observed for both variables. These findings suggest that parents can learn PRT in a group format, resulting in correlated child language gains, thus future controlled studies are warranted.
View details for DOI 10.1007/s10803-010-1027-6
View details for Web of Science ID 000285928200010
View details for PubMedID 20440638
Is Child Psychiatric Service Different When Provided by Attendings Versus Clinicians-in-Training?
2008; 32 (5): 400-404
This study examines the clinical management characteristics of outpatient child and adolescent psychiatric care provided by attendings and clinicians-in-training in an academic institution. The authors hypothesized that no significant differences would exist between initial evaluations conducted by attendings and those conducted by clinicians-in-training.The amount of information obtained during an initial evaluation and the number and type of services recommended postevaluation were assessed for 429 patients treated in the child and adolescent psychiatry clinics at Stanford University by attending psychiatrists and clinicians-in-training.No significant differences were found for the evaluations conducted by attendings and clinicians-in-training for the amount of data collected during an evaluation of the number or type of recommendations made postevaluation.These findings lend themselves to the conclusion that attendings and clinicians-in-training offer comparable services in the assessment of new patients. Study limitations and future areas of study are discussed.
View details for Web of Science ID 000260202200010
View details for PubMedID 18945979
Pre-bereavement meaning and post-bereavement distress in mothers of children who underwent haematopoietic stem cell transplantation
BRITISH JOURNAL OF HEALTH PSYCHOLOGY
2008; 13: 419-433
The purpose of this study was to explore the association of meaning-making with psychological adjustment to bereavement among mothers of children who had undergone haematopoietic stem cell transplantation (HSCT).A prospective research design was used. Regression analyses were conducted to determine the relations between pre-bereavement variables (distress, searching for meaning, and finding meaning) and distress post-bereavement.Thirty-five mothers of children who had undergone HSCT were interviewed at the time of their child's HSCT and 3 months post-bereavement.Mothers who reported searching for meaning at HSCT reported greater post-bereavement distress, and mothers who reported finding meaning at HSCT reported less post-bereavement distress. Distress at HSCT and the number of days between the time of death and the post-bereavement time point were also found to be significant predictors of post-bereavement distress.This study provides partial support for the role of meaning in adjustment to loss.
View details for DOI 10.1348/135910707X204236
View details for Web of Science ID 000258186800004
View details for PubMedID 17535504
Social support from family and friends as a buffer of low spousal support among mothers of critically ill children: A multilevel modeling approach
2008; 27 (5): 593-603
To investigate whether social support from family and friends (family/friend support) attenuated ("buffered") adverse effects of having low spouse support (spousal support) among mothers of children undergoing hematopoietic stem cell transplantation (HSCT).One hundred sixty-three married mothers who were their child's primary caregiver during treatment completed assessments during the child's hospitalization for HSCT and 3-, 6-, and 12-months post-HSCT.Family/friend support and spousal support were assessed during hospitalization. Maternal physical and mental health-related functioning (the main outcome measures) were assessed at all timepoints.Multilevel modeling was used to analyze trajectories of maternal functioning. Findings indicated that mothers with low spousal support and low family/friend support demonstrated the worst functioning across all timepoints. Mothers with low spousal support and high family/friend support demonstrated significantly better functioning, supporting the hypothesized buffering effect. Their functioning compared to the functioning of mothers with high spousal support. Moreover, mothers with high family/friend support demonstrated trajectories of physical health-related functioning that were more stable than the trajectories of mothers with low family/friend support.These findings have clinical implications in addition to advancing knowledge of social support processes among couples coping with the shared stressor of a child's life-threatening illness and treatment.
View details for DOI 10.1037/0278-6220.127.116.113
View details for Web of Science ID 000259350300011
View details for PubMedID 18823186
Optimism and life events as predictors of fear appraisals in mothers of children undergoing hematopoietic stem cell transplantation
2007; 16 (9): 821-833
Although mothers' fear appraisals about their child's future health and well-being affect their own psychological adjustment to their child's hematopoietic stem cell transplantation (HSCT), little is known about antecedents of maternal fear appraisals. This longitudinal study investigated several potential antecedents of these fear appraisals: maternal optimism, recent negative life events, lifetime history of traumatic events, and medical characteristics of the child's disease and HSCT course. One hundred-forty mothers were interviewed during their child's hospitalization for HSCT and at 3-and 6-months post-HSCT. Structural equation modeling was used to test a model of hypothesized relations. Consistent with predictions, lower optimism and a greater number of negative life events were independently associated with greater maternal fear appraisals. Contrary to expectations, lifetime history of trauma was not associated with maternal fear appraisals. Mothers' fear appraisals during their child's hospitalization were, in turn, associated with their fear appraisals up to 6 months later. These data identify a subset of mothers who may be particularly in need of an intervention to increase optimistic coping strategies, improve coping with negative life events, and reduce fear appraisals to improve their adjustment following their child's HSCT.
View details for DOI 10.1002/pon.1132
View details for Web of Science ID 000249572600005
View details for PubMedID 17219398
Amantadine treatment following traumatic brain injury in children
2007; 21 (9): 885-889
The focus of this paper is to review the current literature on the use of amantadine in children who have sustained a head injury.A MEDLINE search was conducted and yielded five papers. They were composed of prospective, retrospective and case study designs. Dosage use and side effect profiles were consistent with expected norms. Efficacy was measures primarily by alertness and arousal and positive results were found for all studies on these dimensions. Behavioural and cognitive measures of outcome yielded mixed results.The studies reviewed for this paper suggest that amantadine is clinically beneficial for children who have sustained head injuries. Double blind placebo controlled trials with larger sample sizes are needed to further substantiate these findings.
View details for DOI 10.1080/02699050701553213
View details for Web of Science ID 000248942600001
View details for PubMedID 17729042
Maternal perspectives on children's health-related quality of life during the first year after pediatric hematopoietic stem cell transplant
JOURNAL OF PEDIATRIC PSYCHOLOGY
2006; 31 (10): 1100-1115
To assess the longitudinal health-related quality of life (HRQL) of children receiving hematopoietic stem cell transplantation (HSCT).Mothers (N = 160) of HSCT recipients aged 5-20 at six US transplant centers completed the Child Health Ratings Inventories (CHRIs), the Disease Impairment Inventory (DSII)-HSCT module, and the Short Form (SF)-36 at baseline, 3, 6, and 12 months.HRQL domain scores at baseline varied by recipient age and program site. Longitudinal data over the first year post-HSCT revealed lowest functioning at baseline and 3 months, with largest improvement in functioning between the 3 and 6-months assessments and continued improvement from 6 to 12 months. Recipients of unrelated donor transplants had steepest declines in functioning at 3 months and great HSCT-specific issues at 3 and 6 months. Among children who survived the first year, functioning at 12 months was similar across transplant types and surpassed baseline scores. Children who did not survive the first year exhibited deterioration in HRQL in the months before death and trajectories were strikingly different than for survivors.This study offers the first glimpse of the 12-month trajectory of HRQL following pediatric HSCT from mothers' perspectives. This study also highlights the importance of and approaches to addressing missing data in longitudinal research.
View details for DOI 10.1093/jpepsy/jsj078
View details for Web of Science ID 000241955500009
View details for PubMedID 16150874
Functional MRI of working memory in paediatric head injury
2005; 19 (7): 549-553
A case study examining the recovery of a 9 year old boy who sustained a severe head injury is reported. The subject sustained damage to the left parietal-occipital and right frontal-parietal regions. Structural and functional imaging and cognitive data were collected at the time of injury and 1 year post-injury. Cognitive assessment revealed improvement over time. Functional imaging at the time of injury revealed minimal activation in the right posterior temporal region. Imaging 1 year post-injury revealed increased activation in the right pre-frontal cortex, bilateral pre-motor cortex and bilateral posterior parietal cortex. This activation pattern is consistent with the performance of unaffected individuals on working memory tasks. These findings differ from those in the adult literature and suggest an alternative pattern of recovery of function in children.
View details for DOI 10.1080/02699050400013576
View details for Web of Science ID 000229622500010
View details for PubMedID 16134743
Mothers' perceptions of benefit following pediatric stem cell transplantation: A longitudinal investigation of the roles of optimism, medical risk, and sociodemographic resources
ANNALS OF BEHAVIORAL MEDICINE
2004; 28 (2): 132-141
This longitudinal study investigated the course and predictors of benefit finding among 144 mothers of children undergoing hematopoietic stem cell transplantation (HSCT), a severely stressful and life-threatening medical procedure.Children's medical risk and mothers' dispositional optimism and sociodemographic resources were examined as predictors of benefit finding. The association between benefit finding and mothers' psychosocial adaptation was also investigated.Assessments occurred during hospitalization for HSCT (Time 1 [T1]) and 6 months later (Time 2 [T2]).Hierarchial multiple regression analyses revealed that predictors of benefit finding differed systematically across assessments, with optimism and medical risk predicting benefit finding at both time points but sociodemographic resources predicting only T2 benefit findings. Benefit finding did not predict psychosocial adaptation until optimism was considered as a moderator of their relation: T1 benefit finding was positively associated with T2 adaptation only for mothers high in optimism.The need for longitudinal research on posttrauma adaptation and the utility of considering the natural history of the trauma are discussed.
View details for Web of Science ID 000224215500009
View details for PubMedID 15454361
Changes in mothers' basic beliefs following a child's bone marrow transplantation: The role of prior trauma and negative life events
JOURNAL OF TRAUMATIC STRESS
2004; 17 (4): 325-333
This longitudinal study examined the relation between life stress and basic beliefs about self-worth and the benevolence and meaningfulness of the world among mothers of children undergoing bone marrow transplantation (BMT). One hundred mothers completed study measures during the child's hospitalization for BMT and 1 year later. Prior trauma and recent negative events were associated with basic beliefs during hospitalization and also with changes in basic beliefs in the subsequent year, with distress mediating some of these relations. Findings also demonstrated relations between basic beliefs and physical and mental functioning. However, each basic belief exhibited different relations with study variables, suggesting the need to investigate them separately.
View details for Web of Science ID 000223401900006
View details for PubMedID 15462540
Practitioners' attitudes toward the use of treatment progress and outcomes data in child mental health services
EVALUATION & THE HEALTH PROFESSIONS
2004; 27 (2): 165-188
This study focused on practitioners' attitudes toward child mental health services data collection and outcomes measurement in university-based and community-based clinics. It is relevant to the burgeoning field of empirically based mental health therapy management because it examines one potential barrier to psychotherapy and pharmacotherapy strategies (i.e., practitioners' attitudes toward outcomes measurement) that are informed by real-time, clinically relevant data. Two site differences were noted regarding the utility of specific questionnaires and the perceived burden of conducting outcomes measurement. At both sites, practitioners held positive attitudes about outcomes measurement. Compared with psychologists and other child mental health specialists, psychiatrists had less favorable attitudes toward outcomes evaluation. Practitioners who rated outcomes evaluation as more important also perceived less burden associated with such evaluation efforts. Increased understanding of the utility of systematic clinical data collection is more likely to occur in an organizational culture in which treatment progress and outcomes measurement is integral to clinical work.
View details for DOI 10.1177/0163278704264058
View details for Web of Science ID 000221253500004
View details for PubMedID 15140293
Anxiety, depressive, and posttraumatic stress disorders among mothers of pediatric survivors of hematopoietic stem cell transplantation
2004; 113 (6): 1700-1708
To examine the prevalence and predictors of anxiety, depression, and posttraumatic stress disorder among mothers of children who underwent hematopoietic stem cell transplantation (HSCT).A total of 111 mothers of children who survived HSCT completed self-report measures of psychological functioning at the time of HSCT and self-report measures and a structured psychiatric interview 18 months after HSCT. Demographic data and medical data were also collected.Approximately 20% of mothers had clinically significant distress reactions. When subthreshold posttraumatic stress disorder was included, nearly one third of mothers met the criterion for persistent distress. Mothers with 1 of the 4 psychiatric diagnoses reported a significantly lower quality of life, suggesting that the diagnoses had an impact on their general quality of life. Mothers who had 1 of the 4 diagnoses at 18 months were younger and had higher anxiety and depressive symptoms at the time of HSCT.A subset of mothers of children who survive HSCT may require psychological intervention. Mothers who are most at risk are younger and evidence anxiety and depressive symptoms at the time of transplantation.
View details for Web of Science ID 000221781500022
View details for PubMedID 15173494
Cognitive processing among mothers of children undergoing bone marrow/stem cell transplantation
2004; 66 (1): 92-103
This study investigated the role of cognitive processing in maternal adjustment to a life-threatening pediatric medical procedure (bone marrow/stem cell transplantation: BMT/SCT).Ninety-one mothers participated in structured interviews about their fears, intrusions, avoidance, and distress regarding their child's BMT/SCT at two time points: during their child's hospitalization and during his/her recovery. Structural equation modeling was used to determine the role of fears, intrusions, and avoidance in mothers' distress.Mothers' fears played a primary role in their adjustment to their child's transplantation. Intrusions mediated the relations of fears with distress at both time points. Mothers' avoidance of thoughts, feelings, and reminders of their child's illness during the child's transplantation was associated with their distress three months later. The child's risk for an unsuccessful transplantation outcome was not associated with mothers' fears or distress during the child's hospitalization, but was associated with mothers' distress during the child's posthospital course of recovery.The results of this study indicate the critical role of mothers' fears, intrusions, avoidance, and the child's transplant risk in maternal distress and have treatment implications for reducing maternal distress during pediatric transplantation.
View details for DOI 10.1097/01.PSY.0000108104.23738.04
View details for Web of Science ID 000188555700014
View details for PubMedID 14747643
Perceived partner critical and avoidant behaviors as predictors of anxious and depressive symptoms among mothers of children undergoing hemopaietic stem cell transplantation
JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
2003; 71 (6): 1076-1083
This prospective study examined the role of perceived partner criticism and avoidance in the anxiety and depressive symptoms of 148 mothers of children undergoing hemopaietic stem cell transplantation (HSCT). The roles of indicators of transplantation risk and posttransplantation medical course were also examined. Perceived partner criticism (e.g., criticizing coping efforts) and perceived partner avoidance (e.g., changing the topic), objective indicators of transplantation risk, and anxiety and depressive symptoms were assessed at the time of HSCT and again 3 and 6 months later. Growth curve modeling analyses indicated that perceived partner criticism was associated with higher average depressive symptoms. However, perceived partner criticism did not predict changes in mother's anxiety. Contrary to predictions, perceived partner avoidance was associated with decreases in maternal anxiety.
View details for DOI 10.1037/0022-006X.71.6.1076
View details for Web of Science ID 000186693600013
View details for PubMedID 14622083
Coping and the course of mother's depressive symptoms during and after pediatric bone marrow transplantation
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
2003; 42 (9): 1055-1068
To evaluate the role of maternal coping strategies in depressive symptoms experienced by mothers of children undergoing bone marrow transplantation (BMT).A total of 207 mothers completed measures of coping and depressive symptoms at the time of the child's BMT, 3 and 6 months post-BMT. The sample was collected between 1998 and 2002. The acceptance rate was 73%. The contribution of demographic, illness and treatment parameters, and mothers' concerns about the child were also evaluated. Growth curve modeling was used to evaluate the role of coping in the course of depressive symptoms. Both main effects and interactions of coping strategies with time of assessment were evaluated.Acceptance and humor were associated with reductions in maternal depressive symptoms, and planning and alcohol/substance use were associated with increases in maternal depressive symptoms. Positive reframing, use of emotional support, and use of religion were associated with the course of depressive symptoms, but the magnitude of associations differed depending on the use of the coping strategies at the time of transplantation. Mothers' fears about the child also predicted depressive symptoms.Acceptance and humor may be targets for behavioral interventions to reduce mothers' depressive symptoms during and after pediatric BMT hospitalization.
View details for DOI 10.1097/01.CHI.0000070248.24125.C0
View details for Web of Science ID 000184921900009
View details for PubMedID 12960705
- Perceived partner critical and avoidant behaviors as predictors of anxious and depressive symptoms among mothers of children undergoing hemopaietic stem cell transplantation Journal of Consulting and Clinical Psychology 2003; 71 (6): 1076-1083
Predictors of PTSD in mothers of children undergoing bone marrow transplantation: The role of cognitive and social processes
JOURNAL OF PEDIATRIC PSYCHOLOGY
2002; 27 (7): 607-617
To investigate the role of cognitive and social processing in posttraumatic stress symptoms and disorder (PTSD) among mothers of children undergoing bone marrow and hematopoietic stem-cell transplantation (BMT/SCT).Questionnaires assessing emotional distress, BMT-related fears, and negative responses of family and friends were completed by 90 mothers at the time of the BMT infusion and 3 and 6 months post-BMT. PTSD symptoms were measured 6 months post-BMT by both paper-and-pencil and structured interview methods.Emotional distress, BMT-related fears, and negative responses of family and friends assessed at the time of BMT hospitalization were predictive of later PTSD symptoms. None of these variables prospectively predicted a PTSD diagnosis as measured by the structured interview.Higher levels of general psychological distress, cognitive interpretations of the threat of the BMT for the child's future functioning, and negative responses of family and friends may place mothers at risk for post-BMT posttraumatic stress symptomatology.
View details for Web of Science ID 000177998600006
View details for PubMedID 12228332
Anxiety and depression in mothers of children undergoing bone marrow transplant: Symptom prevalence and use of the Beck depression and Beck Anxiety Inventories as screening instruments
JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
2001; 69 (6): 1037-1047
This study examined anxiety and depressive symptoms among 115 mothers of children undergoing bone marrow transplant and evaluated the ability of the Beck Anxiety Inventory (BAI; A. T. Beck, N. Epstein, et al., 1988) and the Beck Depression Inventory (BDI; A. T. Beck, 1978) to serve as screening tools for assessing generalized anxiety disorder (GAD), panic disorder (PD), and major depressive disorder (MDD). Mothers with BAI or BDI scores greater than or equal to 14 were administered a structured clinical interview. An additional 20% was randomly selected for interview to determine whether the scale cutoff was an accurate screening method. Among the 64 mothers interviewed, 20% received at least I of the 3 diagnoses. Although the BAI did not demonstrate predictive accuracy in assessing GAD and PD, the BDI did in assessing MDD. The results suggest that a subset of mothers may have an anxiety or depressive disorder and that investigators should use caution before using the BAI as a screening instrument for anxiety disorder.
View details for DOI 10.1037//0022-006X.69.6.1037
View details for Web of Science ID 000172841500017
View details for PubMedID 11777107
Role of the S-1 ' subsite glutamine 215 in activity and specificity of stromelysin-3 by site-directed mutagenesis
1999; 38 (37): 12174-12179
The influence of Gln215 in stromelysin-3 (MMP-11), a residue located in the S1' subsite, was determined by producing three single mutants of this position. As compared to wild-type stromelysin-3, the kinetic parameters K(M) and k(cat) for the degradation of the fluorogenic substrate Dns-Pro-Leu-Ala-Leu-Trp-Ala-Arg-NH(2) (Dns-Leu) by these mutants indicated that the Gln/Leu substitution led to a 4-fold decrease in catalytic efficiency, whereas the mutations Gln/Tyr and Gln/Arg increased this parameter by a factor 10. The cleavage of alpha1-protease inhibitor (alpha1-PI), a natural substrate of stromelysin-3, by these mutants was also determined. Their relative activities for the degradation of alpha1-PI correspond to those observed with the synthetic substrate Dns-Leu. The catalytic efficiency of wild-type stromelysin-3 and its mutants to cleave the P1' analogue of Dns-Leu, containing the unusual amino acid Cys(OMeBn) (Dns-Cys(OMeBn)), was also determined. The values of the specificity factor, calculated as the ratio (k(cat)/K(M))Dns-Cys(OMeBn))/(k(cat)/K(M))Dns-Leu, were observed to vary from 26 for the wild-type stromelysin-3 to 120 for the Gln/Leu mutant and 25 for the Gln/Arg mutant. The Gln/Tyr mutant did not cleave the substrate when its P1' position is substituted by the unusual amino acid Cys(OMeBn). Altogether these observations established that both the catalytic activity and the specificity of stromelysin-3 are dependent on the nature of the residue in position 215. Finally, the cleavage efficiency of the Dns substrates by three representative matrixins, namely, MMP-14 (215 = Leu), MMP-1 (215 = Arg), and MMP-7 (215 = Tyr), was determined. Interestingly, the trends observed for these enzymes were similar to those established for the three mutants of stromelysin-3, pointing out the influence of position 215 toward the selectivity in this family of enzymes.
View details for Web of Science ID 000082834800035
View details for PubMedID 10508422
- Psychiatric assessment of victims of dating violence in a primary care clinic. Clinical Child Psychology and Psychiatry 1999; 4 (3): 427-439
Recovery in pediatric brain injury: Is psychostimulant medication beneficial?
JOURNAL OF HEAD TRAUMA REHABILITATION
1998; 13 (3): 73-81
To assess the effects of methylphenidate on attention, memory, behavior, processing speed, and psychomotor skills of children with closed head injuries.Double-blind, placebo-controlled, crossover design.An outpatient facility of a children's hospital medical center.Ten pediatric subjects identified through chart review. Subjects met baseline scores for hyperactivity (Conner's Hyperactivity Index greater than or equal to 60) and intellectual functioning (Verbal Intelligence Quotient greather than or equal to 70) and achieved minimal scores on two psychometric tests. All subjects evidenced head injury by focal lesions on computed tomography scan and/or sequelae reported at the time of injury. Severity of injury ranged from mild to severe. All subjects were medically stable at the time of testing. Mean time post injury was 2 years, 8 months.Administration of methylphenidate and placebo.Percentage change in scores was calculated to assess differences between baseline and end of methylphenidate/placebo trials.No significant differences between methylphenidate and placebo on measures assessing behavior, attention, memory, and processing speed.The results of the study call into question the effectiveness of methylphenidate in the pediatric head injury population.
View details for Web of Science ID 000074042200007
View details for PubMedID 9582180
Adult psychosocial outcome in early-treated phenylketonuria
JOURNAL OF INHERITED METABOLIC DISEASE
1997; 20 (4): 499-508
Concerns about the psychosocial risk of adults with early-treated phenylketonuria (ETPKU) are predicated on four sources of scientific data: (1) consistent documentation of increased behavioural risk in children with ETPKU; (2) recent evidence of neurocognitive impairment in adults with ETPKU; (3) reports of neuroimaging abnormalities in adults with ETPKU; and (4) preliminary evidence of increased rates of psychiatric disturbance in this population. We studied the psychosocial adjustment of 25 patients, aged 18 years and older, with ETPKU. On most psychosocial outcome measures, patients were indistinguishable from 15 sibling controls. However, on a self-report inventory of psychiatric symptoms, 20% of the patients demonstrated significant morbidity. Psychosocial outcome of these patients was unrelated to concurrent or historical biological dietary disease factors, unlike neurocognitive outcome. A strong relationship was demonstrated, however, between neurocognitive measures and psychosocial morbidity. These findings indicate that a significant minority of patients with ETPKU develop psychosocial difficulties with multiple clinical elevations on a psychiatric inventory. However, most adults with ETPKU cope with the challenges of young adulthood with the same degree of success as their unaffected siblings. Neuropsychological surveillance during childhood and adolescence is important in identifying patients at risk for both neurocognitive and psychosocial morbidity.
View details for Web of Science ID A1997XP41000004
View details for PubMedID 9266385
EARLY-TREATED PHENYLKETONURIA - ADULT NEUROPSYCHOLOGIC OUTCOME
JOURNAL OF PEDIATRICS
1994; 124 (3): 388-392
Twenty-five adults with phenylketonuria that was treated early were compared with 15 unaffected control siblings with respect to intellectual and neuropsychologic measures. Patients were found to have normal intelligence but were significantly lower than their control siblings on measures of intelligence, attention, and complex visuoconstructional ability. Stepwise multiple regression analyses found the patients' intellectual outcome to be best predicted by indexes reflecting early insult to the brain, whereas performance on a measure of novel problem solving was best predicted by concurrent serum phenylalanine level. Different pathophysiologic mechanisms may thus account for cognitive deficits in this population. These results provide further evidence of continuing benefits of dietary adherence into adulthood.
View details for Web of Science ID A1994NA03500007
View details for PubMedID 8120707
- Early treated phenylketonuria: Adult neuropsychological outcome. Journal of Pediatrics 1994; 124: 388-392