Biomedical subjects
Publications and source records attributed to T Spencer.
We present 16 cases, 10 de novo and 6 familial, in which extra structurally abnormal chromosomes (ESACs) were diagnosed prenatally and identified by fluorescence in situ hybridization (FISH) studies with follow up from birth. We review the literature on prenatally diagnosed ESACs arising de novo and suggest a management protocol for these cases.
A female child is described with deletion of chromosome 18 and cardiomyopathy. The clinical features and treatment of the case are described, and the literature of chromosome 18 reviewed.
BACKGROUND: The co-occurrence of attention-deficit hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD) in adults has been the focus of much clinical and scientific inquiry. In this study we examine the effects of ADHD on the transitions from substance abuse to dependence and between different classes of agents of abuse. METHODS: An ADHD sample of 239 consecutively referred adults of both genders with a clinical diagnosis of childhood-onset and persistent DSM-III-R ADHD confirmed by structured interview were compared with 268 non-ADHD healthy adults. RESULTS: ADHD was associated with a twofold increased risk for PSUD. ADHD subjects were significantly more likely than comparisons to make the transition from an alcohol use disorder to a drug use disorder (hazard ratio = 3.8) and were significantly more likely to continue to abuse substances following a period of dependence (hazard ratio = 4.9). CONCLUSIONS: ADHD is associated with a sequence of PSUD in which early alcohol use disorder increases the risk for subsequent drug use disorder, and early substance dependence increases the risk for subsequent substance abuse. If confirmed such developmental pathways might lead to preventive and early intervention strategies aimed at reducing the risk for PSUD in ADHD subjects.
OBJECTIVE: To determine whether spectral analysis of unprocessed radiofrequency (RF) signal offers advantages over standard videodensitometric analysis in identifying the morphology of coronary atherosclerotic plaques. METHODS: 97 regions of interest (ROI) were imaged at 30 MHz from postmortem, pressure perfused (80 mm Hg) coronary arteries in saline baths. RF data were digitised at 250 MHz. Two different sizes of ROI were identified from scan converted images, and relative amplitudes of different frequency components were analysed from raw data. Normalised spectra was used to calculate spectral slope (dB/MHz), y-axis intercept (dB), mean power (dB), and maximum power (dB) over a given bandwidth (17-42 MHz). RF images were constructed and compared with comparative histology derived from microscopy and radiological techniques in three dimensions. RESULTS: Mean power was similar from dense fibrotic tissue and heavy calcium, but spectral slope was steeper in heavy calcium (-0.45 (0.1)) than in dense fibrotic tissue (-0.31 (0.1)), and maximum power was higher for heavy calcium (-7.7 (2.0)) than for dense fibrotic tissue (-10.2 (3.9)). Maximum power was significantly higher in heavy calcium (-7.7 (2.0) dB) and dense fibrotic tissue (-10.2 (3.9) dB) than in microcalcification (-13.9 (3.8) dB). Y-axis intercept was higher in microcalcification (-5.8 (1.1) dB) than in moderately fibrotic tissue (-11.9 (2.0) dB). Moderate and dense fibrotic tissue were discriminated with mean power: moderate -20.2 (1.1) dB, dense -14.7 (3.7) dB; and y-axis intercept: moderate -11.9 (2.0) dB, dense -5.5 (5.4) dB. Different densities of fibrosis, loose, moderate, and dense, were discriminated with both y-axis intercept, spectral slope, and mean power. Lipid could be differentiated from other types of plaque tissue on the basis of spectral slope, lipid -0.17 (0.08). Also y-axis intercept from lipid (-17.6 (3.9)) differed significantly from moderately fibrotic tissue, dense fibrotic tissue, microcalcification, and heavy calcium. No significant differences in any of the measured parameters were seen between the results obtained from small and large ROIs. CONCLUSION: Frequency based spectral analysis of unprocessed ultrasound signal may lead to accurate identification of atherosclerotic plaque morphology.
OBJECTIVE: The authors assessed the experimental noradrenergic compound tomoxetine as an alternative treatment for adult attention deficit hyperactivity disorder (ADHD). METHOD: They conducted a double-blind, placebo-controlled, crossover study of tomoxetine in 22 adults with well-characterized ADHD. RESULTS: Treatment with tomoxetine at an average oral dose of 76 mg/day was well tolerated. Drug-specific improvement in ADHD symptom was highly significant overall and sufficiently robust to be detectable in a parallel-groups comparison restricted to the first 3 weeks of the protocol. Eleven of 21 patients showed improvement after receiving tomoxetine, compared with only two of 21 patients who improved after receiving placebo. Significant tomoxetine-associated improvement was noted on neuropsychological measures of inhibitory capacity from Stroop tests. CONCLUSIONS: This preliminary study showed that tomoxetine was effective in treating adult ADHD and was well tolerated. These promising results provide support for further studies of tomoxetine over an extended period of treatment.
BACKGROUND AND PURPOSE: There is an association between anticardiolipin antibodies (aCL) and ischemic stroke. There are, however, also occasional reports linking aCL with other CNS diseases (OND), particularly with multiple sclerosis (MS). Hence, we studied the specificity of aCL for ischemic stroke. METHODS: Prospective, consecutively identified patients evaluated for aCL (immunoglobulin G [IgG] and immunoglobulin M [IgM] isotypes) were divided into two groups: ischemic stroke (first ever) and OND (stroke-free subjects affected by OND). RESULTS: The ischemic stroke group (n = 300) and the OND (n = 149) differed in the following risk factors: age (64 +/- 14 versus 58 +/- 15 years; p < 0.001) and proportions of African Americans (67% versus 29%; p < 0.001); current cigarette smoker (26% versus 17%; p = 0.028); hypertensive (69% versus 34%; p < 0.001); diabetic (18% versus 7%; p = 0.001); history of angina (16% versus 8%; p = 0.015) or myocardial infarction (15% versus 3%; p < 0.001). There were higher rates of aCL positivity (26% versus 17%; p = 0.050), IgG-aCL > 10 GPL (23% versus 11%; p = 0.003) or IgG aCL > 20 GPL (12% versus 4%; p = 0.012) among the stroke group than among the OND group. No differences in IgG-aCL positivity were found between the MS group and the rest of the OND group but the MS patients had a higher rate of IgM-aCL positivity than the other OND patients. CONCLUSION: IgG-aCL positivity does not appear to be a marker for CNS disease generally but of ischemic stroke.
OBJECTIVE: To assess the effectiveness of mood stabilizers in treating maniclike symptoms in children. METHOD: Subjects were consecutively referred pediatric patients who, at initial intake, satisfied DSM-III-R criteria for mania on a structured diagnostic interview. We systematically reviewed their clinical records to assess (1) the course of maniclike symptoms and (2) all medications prescribed at each follow-up visit. Survival analysis was used to determine the effect of mood stabilizers and other medications on the course of maniclike symptoms. RESULTS: Of the 59 subjects meeting criteria for mania, 44 (75%) exhibited evidence of maniclike symptoms during follow-up. The occurrence of manic symptoms significantly predicted the subsequent prescription of mood stabilizers (rate ratio = 2.9, 95% confidence interval [CI] = 1.6 to 5.5), and use of mood stabilizers predicted decreases in manic symptoms (rate ratio = 4.9, 95% CI = 1.2 to 20.8). However, improvement was slow and associated with a substantial risk for relapse. CONCLUSION: Mood stabilizers were frequently used in children with maniclike symptoms, and their use was associated with significant improvement of maniclike symptoms, whereas use of antidepressant, antipsychotic, and stimulant medications was not.
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The diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults has remained controversial. This paper reviews the empirical evidence to date as to whether the diagnosis of ADHD in adults is valid and consistent with the childhood syndrome. Evidence of descriptive, divergent, predictive, and concurrent validity were examined. The available literature provides evidence that adult ADHD can be reliably diagnosed and that the diagnosis confers considerable power to forecast complications and treatment response. Studies of genetic transmission, specific treatment responses, and abnormalities in brain structure and function in affected individuals are also consistent with studies in childhood ADHD. There is converging evidence that adult ADHD is a not rare, valid clinical diagnosis. In addition, studies suggest that adult and child patients with ADHD may share a similar treatment-responsive, underlying neurobiological substrate.
Stimulant-associated growth deficits in children with attention deficit hyperactivity disorder (ADHD) have long been a concern. Height deficits in preadolescence have been reported, but adult heights have been reported to be uncompromised. It is possible that the catch-up growth that occurs is related to ADHD-associated delayed maturation and not to the cessation of stimulant treatment. To date, no consistent neurohormonal pathophysiology to explain stimulant-associated height deficits has been identified nor have the initial associations of height and weight deficits been replicated. Attention deficit hyperactivity disorder is associated with dysregulation of several neurotransmitter systems, especially the catecholamines, that may alter neuroendocrine function and lead to growth delays. The literature on neuroendocrine aspects of growth and treatment in ADHD and on growth in boys with ADHD who are treated with psychotropics is reviewed, and the results of a controlled study in 124 boys with ADHD are presented. Small but significant differences in height were found between children with and without ADHD. However, the height deficits were evident in early, but not late, adolescence and were not related to the use of psychotropic medications. There was no evidence of weight deficits in children with ADHD relative to control subjects and no relationship between measures of malnutrition and short stature was found. These findings suggest that ADHD may be associated with temporary deficits in height gain through midadolescence that may normalize by late adolescence. This effect appears to be mediated by ADHD and not by its treatment.
OBJECTIVE: To identify similarities and differences in neuropsychiatric correlates in children with Tourette's syndrome (TS) and those with ADHD. METHOD: The sample consisted of children with Tourette's syndrome with ADHD (N = 79), children with Tourette's syndrome without ADHD (N = 18), children with ADHD (N = 563), psychiatrically referred children (N = 212), and healthy controls (N = 140). RESULTS: Disorders specifically associated with Tourette's syndrome were obsessive compulsive disorder (OCD) and simple phobias. Rates of other disorders, including other disruptive behavioral, mood, and anxiety disorders, neuropsychologic correlates, and social and school functioning were indistinguishable in children with Tourette's and ADHD. However, children with Tourette's syndrome plus ADHD had more additional comorbid disorders overall and lower psychosocial function than children with ADHD. CONCLUSIONS: These findings confirm previously noted associations between Tourette's syndrome and OCD but suggest that disruptive behavioral, mood, and anxiety disorders as well as cognitive dysfunctions may be accounted for by comorbidity with ADHD. However, Tourette's syndrome plus ADHD appears to be a more severe condition than ADHD alone.
Mood disorders afflict pediatric patients, cause significant impairment, and interfere with normal development. Increasingly, pediatricians are called on to assess and collaborate with mental health practitioners in medicating children and adolescents with mood disorders. Approaching the juvenile with a primary emphasis on clarifying the diagnoses, determining environmental antecedents and sequelae, and investigating suicide risk enables the pediatrician to institute appropriate treatment. Despite limited data from controlled studies, psychotherapy often is used for mild to moderate depression. Pharmacotherapy is indicated in cases unresponsive to psychotherapy and in severe or suicidal cases. First-line pharmacotherapy for depressed adolescents is usually an SRI followed by the atypical or TCA antidepressants. Bipolar disorder typically requires an aggressive medication regimen, including anticonvulsants, lithium, or a combination, as well as environmental modifications. With severe, difficult, or refractory cases, mental health consultation is recommended to clarify diagnoses and to provide psychotherapy and medication input.
Nonuniform rotation of mechanical intravascular ultrasound transducers may give rise to a geometric distortion of the ultrasound image known as the rotation angle artefact. This investigation studied the influence of different degrees and combinations of catheter shaft angulation on image morphology and the quantitative impact of the artefact using a circular perspex phantom and 3.5 F, 30 MHz Boston Scientific "Sonicath" catheters connected to a Hewlett Packard Sonos intravascular scanner. Major and minor diameters, cross-sectional area and circumference of the phantom lumen were measured and a "distortion index" calculated. Visually apparent geometric distortion was graded from 1 (absent) to 4 (severe). As expected, eccentric transducer location was associated much more frequently with identifiable distortion (70%) than was a concentric location (6%). Greater distortion occurred with increasing degrees of catheter shaft angulation, and was more pronounced in images from older catheters. The lumen area measurements in images in which no artefact was identified were accurate to within +/- 10% in 97% of cases, compared to only 81% of cases when an artefact was noted. The quantitative accuracy of an image in which geometric distortion is identified is thus not reliable. The direction of the quantitative error cannot be confidently predicted in any given case, although the mean lumen area tends to increase as the grade of distortion increases.
Raw 30-MHz intravascular ultrasound data have been captured from postmortem coronary arteries (n = 4) to develop radio frequency analysis techniques for the characterisation of atherosclerotic plaque. Digitised data acquired from positions (n = 8) within diseased sections of artery were compared with the corresponding histology and radiology. Scan-converted images were used to locate regions of interest (ROI = 33) within areas of tissue composition: loose fibrotic tissue (LFT), dense fibrotic tissue (DFT) and calcium (CA). A range of parameters was extracted from the normalised power spectrum of each ROI within the bandwidth 17-42 MHz. Significant discrimination between LFT/DFT and between LFT/CA was provided by maximum power and spectral slope (dBMHz-1). However, the greatest discriminative power was given by the y-axis (0 Hz) intercept of the spectral slope: LFT/DFT (p = 0.001); LFT/CA (p = 0.0001); and DFT/CA (p = 0.089).
Visual assessment of intravascular ultrasound (IVUS) video images cannot reliably identify thrombus. We examined if texture analysis of radiofrequency (r.f.) data or videodensitometric data (VD) could distinguish thrombi of different ages and cell compositions. Whole human blood (red clot = RC), platelet-rich plasma (white clot = WC) and plasma (n = 6/group) were imaged at 4 and 24 h with 30 MHz IVUS transducers. At 4 h, VD- and r.f.-based analyses revealed significant differences between RC and WC with variance (VD red 26.4 +/- 2.5, white 33.9 +/- 7.8; r.f. red 1.4 +/- 0.5, white 4.9 +/- 1.3), kurtosis (VD red 0.29 +/- 0.9, white 0.23 +/- 0.3) and skewness (VD red 0.23 +/- 0.13, white 0.35 +/- 0.52; r.f. red 0.06 +/- 0.01, white -0.06 +/- 0.05). Also mean grey-level from both data sets was higher in RC (VD 134.8 +/- 18.0; r.f. -13.3 +/- 1.2) than in WC (VD 105.3 +/- 17.4, r.f. 16.5 +/- 2.2) (p < 0.01). With increasing time, variance increased in WC (5.5 +/- 1.5 at 24 h) and decreased in RC (0.9 +/- 0.3.3 at 24 h). The more heterogeneous structure of WC may be distinguished from that of RC using texture analysis of either VD or r.f.-signals.
OBJECTIVE: To determine the predictability and stability of desipramine (DMI) concentrations in a clinically treated sample of children, estimating the risk of developing potentially toxic DMI levels at a higher dose after a most recent level in a clinically acceptable range. METHOD: Subjects were 90 consecutive psychiatrically referred children and adolescents treated with DMI with at least two assays of serum DMI concentrations (462 pairs). Assay data were analyzed after log transformation and linear regression. RESULTS: Despite wide between-patient variability in serum DMI levels at the same dose, future within-subject DMI blood levels were highly predictable from knowledge of current levels, current dose, and the future dose. When the DMI serum level was 200 to 300 ng/ml, there was a 7.0% risk for subsequent levels at the same dose to exceed 300 ng/mL, but potentially toxic levels above 500 ng/mL were very infrequent (1.7%). CONCLUSIONS: Although the results of this naturalistic clinical study may not generalize to other situations, the results indicate a reasonable stability, predictability, and safety of DMI levels in individual psychiatrically treated children that result from clinically chosen dose changes.
OBJECTIVE: To clarify the nosological status of children with attention-deficit hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar disorder (BPD). METHOD: Blind raters and structured psychiatric interviews were used to examine 140 children with ADHD, a sample of 120 non-ADHD comparisons, and their 822 first-degree relatives. Data analyses tested specific hypotheses about the familial relationship between ADHD and BPD. RESULTS: After stratifying the ADHD sample into those with and without BPD, the authors found that (1) relatives of both ADHD subgroups were at significantly greater risk for ADHD than relatives of non-ADHD controls; (2) the two subgroups did not differ significantly from one another in their relatives' risk for ADHD; (3) a fivefold elevated risk for BPD was observed among relatives when the proband child had BPD but not when the proband had ADHD alone; (4) an elevated risk for major depression with severe impairment was found for relatives of ADHD + BPD probands; (5) both ADHD and BPD occurred in the same relatives more often than expected by chance alone; and (6) there was a trend for random mating between ADHD parents and those with mania. CONCLUSIONS: The data suggest that comorbid ADHD with BPD is familially distinct from other forms of ADHD and may be related to what others have termed childhood-onset BPD.
We evaluated the association between attention deficit hyperactivity disorder (ADHD) and the age of onset of psychoactive substance use disorders (PSUD) in adults with ADHD. We hypothesized that ADHD and psychiatric comorbidity would be risk factors for early onset PSUD. We compared 120 referred adults having a clinical diagnosis of childhood-onset ADHD with 268 non-ADHD adults. All diagnoses were obtained using DSM-III-R based structured psychiatric interviews. We used group comparisons of age at onset and Cox proportional hazard models to examine the development of PSUD over time. ADHD was associated with earlier onset of PSUD independently of psychiatric comorbidity. Conduct and juvenile bipolar disorders conferred a significantly increased risk for early onset PSUD independently of ADHD. Psychiatric disorders commonly emerged before the onset of PSUD in both groups. Persistent ADHD with and without psychiatric comorbidity was associated with adolescent onset PSUD. In addition, comorbidity with conduct and juvenile bipolar disorders predicted very early onset PSUD in both ADHD and non-ADHD individuals. These findings confirm and extend previous findings documenting important associations between PSUD and psychiatric comorbidity including persistent ADHD.