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T Spencer

Publications and source records attributed to T Spencer.

At least 37 records · Page 2Linked to original sources

Pediatric mania: a developmental subtype of bipolar disorder?

Despite ongoing controversy, the view that pediatric mania is rare or nonexistent has been increasingly challenged not only by case reports, but also by systematic research. This research strongly suggests that pediatric mania may not be rare but that it may be difficult to diagnose. Since children with mania are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset mania may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. The major difficulties that complicate the diagnosis of pediatric mania include: 1) its pattern of comorbidity may be unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder, aggression, and conduct disorder; 2) its overlap with substance use disorders; 3) its association with trauma and adversity; and 4) its response to treatment is atypical by adult standards.

Adolescent↗

Attention-deficit/hyperactivity disorder in adults: an overview.

To assess the validity of adult attention-deficit/hyperactivity disorder (ADHD), we reviewed clinical, family, psychopharmacologic, neurobiological, and outcome studies. We found multiple reports describing adults with clinical features highly reminiscent of the childhood ADHD. These adults, who are impulsive, inattentive, and restless, have the clinical "look and feel" of ADHD children. As with their childhood counterparts, many adults with ADHD suffer from antisocial, depressive, and anxiety disorders. They also show clinically significant impairments--histories of school failure, occupational problems, and traffic accidents. Studies of biological features show correspondences between child and adult cases of ADHD. Both show familial aggregation and a characteristic profile of neuropsychologic deficits; an emerging neuroimaging literature suggests that abnormalities in the same brain regions underlie both the child and adult forms of the disorder. Although these converging lines of evidence support the validity of ADHD in adults, follow-up studies of ADHD children have yielded ambiguous results. This ambiguity is in part due to differences in how researchers define the persistence of ADHD, a problem that suggests future research focus on how best to diagnose ADHD in adulthood.

Adult↗

Non-stimulant treatments for ADHD.

We reviewed the literature of medication trials in ADHD to evaluate the scope of the available non-stimulant treatments. A variety of compounds with a common noradrenergic/ dopaminergic activity have shown documented anti-ADHD activity. There is a substantial body of literature documenting the efficacy of tricyclic antidepressants on ADHD in over 1,000 subjects. In addition, the atypical antidepressant bupropion and the novel noradrenergic specific antidepressant tomoxetine have also been documented to be effective in the treatment of ADHD in controlled clinical trials. Despite wide use, the scientific base supporting the efficacy of alpha-2, noradrenergic agonists continues to be limited. Several lines of evidence provide preliminary support for the potential benefits of cholinergic cognitive enhancing drugs in such as anticholinesterase inhibitors (tacrine, donepezil) as well as novel nicotinic analogues (ABT-418). Despite these promising results, more research is needed on alternative pharmacologic treatments for the treatment of ADHD.

Adolescent↗

Classification of arterial plaque by spectral analysis of in vitro radio frequency intravascular ultrasound data.

To test whether radio-frequency analysis of coronary plaques predicts the histological classification, r.f. data were collected using a 30 MHz intravascular ultrasound scanner. Two hundred ninety-nine regions-of-interest from eight postmortem coronary arteries were selected and identified by histology as falling into one of seven different tissue types. These are loose fibrous tissue (n = 78), moderate fibrous tissue (n = 27), dense fibrous tissue (n = 33), microcalcification (n = 14), calcified plaque (n = 55), lipid/fibrous mixture (n = 51) and homogeneous areas of lipid pool (n = 29). On the basis of a previous study, four spectral parameters were calculated for each of the regions-of-interest: maximum power (dB), mean power (dB), spectral slope (dB/MHz) over the bandwidth 18-35 MHz and the intercept of the spectral slope with the 0 Hz axis (dB). A minimum-distance classifier using the Mahalanobis (1948) distance was applied to the data. Following resubstitution of the training data into the classifier, the total correctly classified was 54%. The data were reclassified using three broader tissue groups: (1) calcified plaque, (2) lipid pool and (3) a mixed fibrous category, incorporating loose fibrous tissue, moderate fibrous tissue, dense fibrous tissue, lipid/fibrous mixture and microcalcification. The total correctly classified was 86%. Using "leave-one-out" cross-validation, the classification rates were 48% for seven tissue subgroups and 83% for three broader categories of tissue type.

Cadaver↗

Informativeness of structured diagnostic interviews in the identification of Tourette's disorder in referred youth.

Although specialized programs have greatly advanced the treatment of youth with Tourette's disorder (TD), not all children with TD reach such programs, raising questions as to whether TD is adequately identified outside specialized settings. There is thus a need for evidence that cases identified in the nonspecialty setting are "true cases." Because structured diagnostic interview methodology can reduce errors of omission, this approach can facilitate the identification of TD in referred youth outside specialized programs. Similarities between cases ascertained in specialty and nonspecialty settings would suggest that those identified in the nonspecialty setting were indeed "true cases." Comparisons were made between youth with TD ascertained through a specialized TD program who had both a structured diagnostic interview-derived diagnosis of TD plus an expert evaluation of TD (N = 103), with youth ascertained through a non-TD specialized pediatric psychopharmacology program who had a structured diagnostic interview-derived diagnosis of TD (N = 92). Irrespective of ascertainment source, children with structured interview-derived diagnosis of TD shared similar correlates in terms of tic severity, mean age of onset and duration of tics, as well as patterns of comorbidity well known to be associated with TD in clinical samples. Children meeting diagnostic criteria for TD on structured diagnostic interviews share similarities and patterns of clinical correlates, irrespective of ascertainment through a specialized TD or non-TD specialized clinic. These findings support the usefulness of structured diagnostic interview methodology as a diagnostic aid for the identification of TD in non-TD specialized settings and facilitate delineation of patterns of comorbidity.

Adolescent↗

Molecular cloning and functional analysis of three type D endogenous retroviruses of sheep reveal a different cell tropism from that of the highly related exogenous jaagsiekte sheep retrovirus.

Integrated into the sheep genome are 15 to 20 copies of type D endogenous loci that are highly related to two exogenous oncogenic viruses, jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV). The exogenous viruses cause infectious neoplasms of the respiratory tract in small ruminants. In this study, we molecularly cloned three intact type D endogenous retroviruses of sheep (enJS56A1, enJS5F16, and enJS59A1; collectively called enJRSVs) and analyzed their genomic structures, their phylogenies with respect to their exogenous counterparts, their capacity to form viral particles, and the expression specificities of their long terminal repeats (LTRs). In addition, the pattern of expression of enJSRVs in vivo was studied by in situ hybridization. All of the three enJSRV proviruses had open reading frames for at least one of the structural genes. In particular, enJS56A1 had open reading frames for all structural genes, but it could not assemble viral particles when highly expressed in human 293T cells. We localized the defect for viral assembly in the first two-thirds of the gag gene by making a series of chimeras between enJS56A1 and the exogenous infectious molecular clone JSRV(21). Phylogenetic analysis distinguished five ovine type D retroviruses: enJSRV groups A and B, ENTV, and two exogenous JSRV groups (African versus United Kingdom/North America isolates). Transient transfection assays indicated that the LTRs of the three enJSRVs were not preferentially active in differentiated lung epithelial cells. This suggests that the pulmonary tropic JSRV developed from a type D retrovirus that did not have lung specificity. Consistent with this, in situ hybridization of a panel of normal ovine tissues revealed high expression of enJSRV mRNA in the luminal epithelium and glandular epithelium of the uterus; lower expression was localized in the lamina propria of the gut and in the bronchiolar epithelium of the lungs.

Amino Acid Sequence↗

Family study of girls with attention deficit hyperactivity disorder.

OBJECTIVE: Because attention deficit hyperactivity disorder (ADHD) is relatively infrequent among girls, little is known about the causes of ADHD in girls. To help fill this gap in the literature, the authors assessed the familial transmission of ADHD in families ascertained through girls. METHOD: Interviewers who were blind to diagnosis administered structured psychiatric interviews to 140 girls with ADHD and their 417 first-degree relatives and to 122 girls without ADHD and their 369 first-degree relatives. RESULTS: The relatives of the ADHD girls had a significantly higher prevalence of ADHD, according to either the DSM-III-R or DSM-IV definition, than the relatives of the comparison girls. However, this did not differ from the prevalence the authors reported previously for families of boys with ADHD. Like the boys' families, the relatives of the girl probands also had significantly higher prevalences of antisocial, mood, anxiety, and substance use disorders, although the prevalence of familial antisocial disorders was lower than had been observed in the boys' families. There was no association between the DSM-IV subtypes of the probands and relatives. CONCLUSIONS: The familial transmission of ADHD and comorbid disorders generalizes to families of girls with ADHD. Neither proband gender nor subtype influences the familial transmission of ADHD.

Adolescent↗

Development of diagnostic concentrations for monitoring Bacillus thuringiensis resistance in European corn borer (Lepidoptera: Crambidae).

Two candidate diagnostic concentrations of the Cry1Ab and Cry1Ac toxins from Bacillus thuringiensis corresponding to the LC99 and EC99 (effective concentration that causes 99% growth inhibition) for European corn borer, Ostrinia nubilalis (Hübner), were determined based on previously obtained baseline data. Validation experiments using field-collected European corn borer populations from across North America showed that for Cry1Ab, a concentration corresponding to the upper limit of the 95% confidence interval of the LC99, produced mortality > 99% for all populations tested. However, for Cry1Ac, adjustments and further validation are probably necessary. Development of B. thuringiensis resistance monitoring programs that rely on diagnostic techniques are discussed.

Animals↗

Baseline susceptibility of the corn earworm (Lepidoptera: Noctuidae) to the Cry1Ab toxin from Bacillus thuringiensis.

Susceptibility to Cry1Ab toxin from Bacillus thuringiensis (Bt) was determined for 12 field populations of neonate corn earworm, Helicoverpa zea (Boddie), from the United States. Earworm larvae were exposed to artificial diet treated with increasing Bt concentrations, and mortality and growth inhibition were evaluated after 7 d. The range of variation in Bt susceptibility indicated by growth inhibition was very similar to that indicated by mortality. Although interpopulation variation in susceptibility to both proteins was observed, the magnitude of the differences was small (less than or equal to fivefold). These results suggest that the observed susceptibility differences reflect natural variation in Bt susceptibility among corn earworm populations rather than variation caused by prior exposure to selection pressures. Therefore, corn earworms apparently are susceptible to Bt toxins across most of their geographic range.

Animals↗

Pharmacotherapy of attention deficit hyperactivity disorder.

Despite a large body of literature documenting the effectiveness of medication in the treatment of ADHD, there has been public and professional concern regarding the possible inappropriate diagnosis and prescription of ADHD medications. Recently the Council of Scientific Affairs of the American Medical Association addressed these concerns in a scholarly review. Several factors were identified that contributed to existing controversies: (1) Like most psychiatric disorders, diagnostic criteria for ADHD are based on history and behavioral assessment. There are no pathognomonic laboratory or radiologic tests to confirm the diagnosis. (2) Attention deficit hyperactivity disorder is a chronic disorder and requires extended treatment. (3) Treatment includes potentially abusable medications. After a review of the voluminous literature, this distinguished panel concluded that ADHD is one of the best researched disorders in medicine; in fact, the overall data on its validity are far more compelling than for many other medical conditions. They also concluded that there was little evidence of widespread overdiagnosis or misdiagnosis of ADHD or of widespread overprescription of stimulants by physicians. Consistent with the current emphasis on cognitive dysregulation in ADHD, treatment concerns have expanded from a primarily behavioral focus to include enhancement of executive functions in scholastic as well as other settings. Although stimulants have been the most studied compounds, there is a considerable body of literature indicating an important role for other psychopharmacologic agents. Noradrenergic and dopaminergic modulation appears to be necessary for effective anti-ADHD treatment. In addition, promising evidence of newer cholinergic agents may provide other useful alternatives. As with all psychiatric disorders, comorbid conditions are prominent and may lead to high morbidity and disability if not addressed. As with other areas of medicine, it is sometimes necessary to use multiple agents to treat comorbidity or to achieve an effective response.

Adolescent↗

The course of Tourette's disorder: a literature review.

With the goal of evaluating the available literature on the course of Tourette's disorder, we conducted a systematic literature search through electronic databases for pertinent scientific articles in English with a minimum of 20 subjects. We also examined bibliographies of papers identified in this manner for additional sources. We found only 16 articles; most consisted of retrospective reports on treated samples. Overall, the available literature suggests that Tourette's disorder follows a remitting course in a sizeable number of individuals. Little has been published regarding predictors of remission or persistence. More work is needed using longitudinal prospective studies to better define the course and outcome of Tourette's disorder.

Adolescent↗

Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder.

This review revisits the thesis that a dysregulation of the central noradrenergic networks may underlie the pathophysiology of ADHD. We review the pertinent neurobiological and pharmacological literature on ADHD. The noradrenergic system has been intimately associated with the modulation of higher cortical functions including attention, alertness, vigilance and executive function. Noradrenergic activation is known to profoundly affect the performance of attention, especially the maintenance of arousal, a cognitive function known to be deficient in ADHD. Data from family, adoption, twin, and segregation analysis strongly support a genetic hypothesis for this disorder. Although molecular genetic studies of ADHD are relatively new and far from definitive, several replicated reports have found associations between ADHD with DAT and D4 receptor genes. Brain imaging studies fit well with the idea that dysfunction in fronto-subcortical pathways occurs in ADHD with its underlying dysregulation of noradrenergic function. A wealth of pharmacological data (within and without the stimulant literature) provides strong evidence for selective clinical activity in ADHD for drugs with noradrenergic and dopaminergic pharmacological profiles. Available research provides compelling theoretic, basic biologic and clinical support for the notion that ADHD is a brain disorder of likely genetic etiology with etiologic and pathophysiologic heterogeneity. Neurobiological and pharmacological data provide compelling support for a noradrenergic hypothesis of ADHD and suggest that drugs with noradrenergic activity may play an important role in the therapeutics of this disorder.

Arousal↗

The 4-year course of tic disorders in boys with attention-deficit/hyperactivity disorder.

BACKGROUND: Despite long-standing clinical concerns, relatively little is known about the comorbidity between attention-deficit/hyperactivity disorder (ADHD) and tic disorders. Therefore, we examined tic disorders in an ongoing prospective follow-up study of male subjects with ADHD, a sample unselected for any comorbid disorder. METHODS: One hundred twenty-eight male children and adolescents with ADHD and 110 male controls were comprehensively evaluated at baseline and 4 years later. We characterized tic disorders along with a wide range of neuropsychiatric correlates, including other comorbid disorders and indices of psychosocial function in multiple domains (school, cognitive, social, and family). RESULTS: Compared with controls, subjects with ADHD showed more tic disorders at baseline and more new onsets were reported at follow-up. Attention-deficit/hyperactivity disorder and tic disorders appeared to be independent in course: in contrast to low rates of ADHD remission, tic disorders mostly remitted. The age-adjusted rate of ADHD remission was 20% and that of tic remission, 65%. Tic disorders had little effect on the psychosocial functioning of subjects with ADHD. CONCLUSIONS: These findings suggest that comorbidity with a tic disorder has a limited effect on ADHD outcome. However, because of the relatively small sample of subjects with tic disorders, our conclusions should be considered preliminary until confirmed in larger studies of medicated and unmedicated children with ADHD with and without tic disorders.

Adolescent↗

Attention-deficit/hyperactivity disorder and comorbidity.

Studies of children with ADHD consistently document high rates of comorbid psychiatric conditions, including conduct disorders, depression and other mood disorders, anxiety disorders, and tic disorders. In diagnosing children with ADHD, one must be careful not to dismiss other symptomatology as secondary. Poor social skills, problems with parents, low academic functioning, and other correlates of ADHD can be construed as causal factors. Although these should not be ignored, neither should the possibility that a child suffers from another psychiatric disorder that might respond to appropriate pharmacotherapy. A variety of behavior rating scales are available to the practitioner as the first steps in this process.

Attention Deficit Disorder with Hyperactivity↗

Systematic chart review of the pharmacologic treatment of comorbid attention deficit hyperactivity disorder in youth with bipolar disorder.

The objective of this study was to evaluate pharmacological approaches for attention deficit hyperactivity disorder (ADHD) in children with bioplar disorder and comorbid ADHD. The medical charts of 38 patients with diagnoses of both Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised ADHD and bipolar disorder were reviewed over multiple visits to assess improvement and prescription patterns. Logistic regression was used to model the probability of improvement at each visit, and robust standard errors were estimated in order to account for correlation among individuals using Huber's correction for clustered data. The proportion of visits at which ADHD symptoms were rated as improved following initial improvement in manic symptoms was 7.5 times greater than before initial improvement of manic symptoms. The recurrence of manic symptoms following their initial stabilization significantly inhibited ADHD response to medication. Although tricyclic antidepressants (TCAs) significantly increased the probability of ADHD improvement following mood stabilization, there was also a significant association between treatment with TCAs and relapse of manic symptoms. Our results support the hypothesis that mood stabilization is a prerequisite for the successful pharmacologic treatment of ADHD in children with both ADHD and manic symptoms. Although TCAs can be helpful in the management of ADHD children with manic symptoms, these drugs should be used with caution since they can also have a destabilizing effect on manic symptoms.

Adolescent↗

Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder.

OBJECTIVE: To assess the risk for substance use disorders (SUD) associated with previous exposure to psychotropic medication in a longitudinal study of boys with attention-deficit/hyperactivity disorder (ADHD). METHODS: The cumulative incidence of SUD throughout adolescence was compared in 56 medicated subjects with ADHD, 19 nonmedicated subjects with ADHD, and 137 non-ADHD control subjects. RESULTS: Unmedicated subjects with ADHD were at a significantly increased risk for any SUD at follow-up compared with non-ADHD control subjects (adjusted OR: 6.3 [1.8-21.6]). Subjects with ADHD medicated at baseline were at a significantly reduced risk for a SUD at follow-up relative to untreated subjects with ADHD (adjusted OR: 0.15 [0.04-0.6]). For each SUD subtype studied, the direction of the effect of exposure to pharmacotherapy was similar to that seen for the any SUD category. CONCLUSIONS: Consistent with findings in untreated ADHD in adults, untreated ADHD was a significant risk factor for SUD in adolescence. In contrast, pharmacotherapy was associated with an 85% reduction in risk for SUD in ADHD youth.

Adolescent↗

Absence of effect of stimulants on the phamacokinetics of desipramine in children.

We conducted a retrospective chart review to examine the pharmacokinetic interaction between desipramine and the stimulants methylphenidate and dexedrine using routinely monitored desipramine serum concentrations in children receiving desipramine either alone or with a stimulant. Subjects were 142 children and adolescents (age 6-17 yrs; 113 taking desipramine, 29 taking desipramine-stimulants) in whom 401 dose- and weight-normalized serum concentrations were evaluated (333 desipramine, 68 desipramine-stimulants). Desipramine pharmacokinetic parameters were similar for both groups, including mean weight-corrected dose (3.66+/-1.36 mg/kg, desipramine; 3.66+/-1.09 mg/kg, desipramine-stimulants; p=0.97), weight- and dose-normalized serum concentrations (47.26+/-39.26 [microg/L]/[mg/kg], desipramine, 39.02+/-19.92 [microg/L]/[mg/kg], desipramine-stimulants; p=0.09), and clearance (0.690+/-0.913 [L/kg]/hr, desipramine; 0.613+/-0.514 [L/kg]/hr, desipramine-stimulants; p=0.499). When stratified by age, gender, and type of stimulant, no difference was detected (p>0.05) between groups. Our findings indicate the absence of a clinically significant interaction between desipramine and stimulants.

Adolescent↗