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Biomedical subjects

T Spencer

Publications and source records attributed to T Spencer.

At least 19 recordsLinked to original sources

Variability, interaction and change in the atmosphere-ocean-ecology system of the Western Indian Ocean.

Traditional ideas of intraseasonal and interannual climatic variability in the Western Indian Ocean, dominated by the mean cycle of seasonally reversing monsoon winds, are being replaced by a more complex picture, comprising air-sea interactions and feedbacks; atmosphere-ocean dynamics operating over intrannual to interdecadal time-scales; and climatological and oceanographic boundary condition changes at centennial to millennial time-scales. These forcings, which are mediated by the orography of East Africa and the Asian continent and by seafloor topography (most notably in this area by the banks and shoals of the Mascarene Plateau which interrupts the westward-flowing South Equatorial Current), determine fluxes of water, nutrients and biogeochemical constituents, the essential controls on ocean and shallow-sea productivity and ecosystem health. Better prediction of climatic variability for rain-fed agriculture, and the development of sustainable marine resource use, is of critical importance to the developing countries of this region but requires further basic information gathering and coordinated ocean observation systems.

Animals↗

Re-examining comorbidity of Obsessive Compulsive and Attention-Deficit Hyperactivity Disorder using an empirically derived taxonomy.

BACKGROUND: Using an empirically derived instrument to reduce the assessor bias inherent in structured diagnostic interviews, we sought to re-examine and validate the putative comorbidity between Obsessive Compulsive Disorder (OCD) and Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. METHOD: We examined the correlation between Child Behavior Checklist (CBCL) syndrome, competence, and composite scores in children with: 1) OCD plus ADHD (OCD + ADHD), N = 47; 2) OCD without comorbid ADHD (OCD), N = 33; 3) ADHD without comorbid OCD (ADHD) N = 43; and 4) comparison controls recruited from general pediatric clinics,N = 32. RESULTS: CBCL findings in our ADHD children were similar to previous findings reported in ADHD youth, irrespective of the presence or absence of comorbid OCD. Comorbid youth generally had additive scores on the CBCL scales, reflecting the independent contribution of symptomatic and functional impairment from each disorder. CONCLUSION: These findings suggest that when ADHD-like symptoms are seen in OCD youth, they reflect a true comorbid state of OCD plus ADHD. The CBCL may provide a rapid assessment tool to identify comorbid ADHD in OCD youth.

Adolescent↗

High-level expression of cancer/testis antigen NY-ESO-1 and human granulocyte-macrophage colony-stimulating factor in dendritic cells with a bicistronic retroviral vector.

Tumor-specific genes delivered to dendritic cells (DCs) have been used for the generation of cytotoxic T cells (CTLs), but their application has been limited on the one hand by low viral titers resulting in low transduction efficiency and poor protein production, and on the other hand by immunogenicity of the selectable marker and poor viability of the DCs. We addressed these limitations by creating a multipurpose master vector (pMV) and cloning the tumor gene NY-ESO-1, which is highly expressed in more than 50% of advanced myeloma patients. pMV was constructed from a Moloney murine leukemia virus (Mo-MuLV)-based retroviral backbone with the following features: (1) an extended packaging signal to achieve high viral titers, (2) a splice acceptor region to facilitate protein production, (3) a nonimmunogenic selectable marker, dihydrofolate reductase-L22Y (DHFR(L22Y)), to exclude the generation of CTLs against the selectable marker, (4) an internal ribosomal entry site between the tumor-specific gene (NY-ESO-1) and the selectable marker DHFR(L22Y) for coexpression of two heterologous gene products from a single bicistronic mRNA, minimizing the possibility of differential expression of these two genes, and (5) human granulocyte-macrophage colony-stimulating factor (hGM-CSF) cDNA driven by the human T-lymphotropic virus promoter to enhance DC function and viability. Recombinant virus of pMV-NY-ESO-1 was generated with vesicular stomatitis virus G envelope protein (VSV-G) in the GP2-293 cell line for efficient transduction. We present evidence that the DC phenotype is unaltered after transduction and that more than 85% of DCs express NY-ESO-1, which secrete approximately 40 ng of GM-CSF per 10(6) DCs.

Antigens, CD34↗

Endogenous retroviruses related to jaagsiekte sheep retrovirus.

Ovine betaretroviruses consist of exogenous viruses [jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus, (ENTV)] associated with neoplastic diseases of the respiratory tract and 15-20 endogenous viruses (enJSRV) stably integrated in the ovine and caprine genome. Phylogenetic analysis of this group of retroviruses suggests that the enJSRV can be considered as 'modern' endogenous retroviruses with active, exogenous counterparts. Sequence analysis of JSRV, ENTV and enJSRV suggests that enJSRV do not directly contribute to the pathogenesis of ovine pulmonary adenocarcinoma (OPA) or enzootic nasal tumor through large-scale recombination events, but small-scale recombination or complementation of gene function cannot be excluded; experiments involving enJSRV-free sheep, which have not been found, would be needed to investigate this possibility. Evidence of expression of enJSRV structural proteins in tissues of the reproductive tract and lung implies that they do not have a primary role in disease. However, experimental exploitation of exogenous/endogenous retrovirus sequence differences by producing chimeras has been useful in establishing the determinants of JSRV Env-induced transformation. Even if enJSRV do not have a direct role in OPA, their expression during ontogeny or in neonatal life may impact the likelihood of exogenous JSRV infection and disease outcome via the induction of immunological tolerance. Aside from any role in disease, enJSRV loci may serve as useful genetic markers in the sheep and their frequent expression in the reproductive tract of the ewe may portend an important physiologic role in sheep.

Age Factors↗

Ophthalmologic sequelae of thermal burns over ten years at the Alfred Hospital.

PURPOSE: To study the ocular outcomes of facial burns over a 10-year period at the Alfred Hospital; in particular, to investigate the impact of 3 variables (grading of burn, use of prophylactic ocular surface lubrication, and timing of ophthalmologic referral) on the requirements for eyelid surgery. METHODS: A retrospective review of patients admitted to the Alfred Hospital (from October 1990 to October 2000) after thermal burns with facial, eyelid, and ocular involvement. RESULTS: Sixty-six patients were identified with facial burns involving the lids or eyes, having been admitted over a 10-year period. Of these 66, 7 died of complications of the burns and 12 required eye or eyelid surgery. Of those patients treated with prophylactic ocular surface lubrication, the rate of ocular surgery was 18.4% as opposed to 30% when no prophylaxis was used. The higher the percentage of total burn, the later the referral was made. Of those with severe eyelid burns, 100% had eyelid surgery and 50% of moderate burns had eyelid surgery. Sixty percent of moderate eyelid burns that required surgery did not receive prophylaxis. Thirty-four of 66 patients had acute corneal involvement, but only 3 eyes of 118 had long-term corneal morbidity. CONCLUSIONS: The requirement for eyelid surgery was closely related to the severity of the eyelid burn. The presence of an acute corneal burn with epithelial loss was not a poor prognosticator. The use of prophylactic ocular surface lubrication may provide early corneal protection, thereby minimizing ulceration in patients who may otherwise have required surgery, especially in those with mild to moderate exposure. Prompt ophthalmologic examination and the early use of prophylactic ocular surface lubrication for the cornea are associated with less need for eyelid surgery in patients with moderate eyelid burns.

Cornea↗

Guidelines and algorithms for the use of methylphenidate in children with Attention-Deficit/ Hyperactivity Disorder.

OBJECTIVE: To review published algorithms for guiding the use of methylphenidate (MPH) in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. METHODS: A consensus roundtable of 12 experts was convened to review the evidence for the safety and efficacy of MPH in the treatment of ADHD, as well as the published algorithms and practice guidelines for using MPH. The experts reviewed the algorithms for practicality and acceptability by clinicians. RESULTS: Algorithms that included MPH commonly selected it as the initial medication to be employed in the treatment of children with ADHD. Factors involved included its high efficacy, good safety record, and the ubiquitous nature of its appearance in the ADHD treatment literature. CONCLUSIONS: MPH should be considered as the first medication to be used in a treatment algorithm for children and adolescents with ADHD.

Adolescent↗

Methylphenidate in treatment of adults with Attention-Deficit/Hyperactivity Disorder.

Attention-Deficit/Hyperactivity Disorder (ADHD) can persist into adulthood with a continuation of the pattern of childhood psychopathology, cognition and functioning. Adult comorbidities include substance use disorders, antisocial personality disorder, anxiety, and depression. Studies have shown that as in children, methylphenidate treatment for adults can lead to a robust, dose-dependent improvement in ADHD symptoms. Future research is needed to evaluate the safety and efficacy of long-term treatment with methylphenidate (MPH).

Adolescent↗

Non-stimulant treatment for Attention-Deficit/Hyperactivity Disorder.

A variety of compounds with a common noradrenergic/dopaminergic activity have shown documented anti-Attention-Deficit/Hyperactivity Disorder (ADHD) activity. There is a substantial body of literature documenting the efficacy of tricyclic antidepressants on ADHD in over 1,000 subjects. There is an equally large database on the efficacy of the specific norepinephrlne reuptake inhibitor, atomoxetine, of greater than 2,000 Individuals. In addition, the atypical antidepressant buproplon also has 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 is somewhat limited. Several lines of evidence provide preliminary support for the potential benefits of cholinergic cognitive enhandng drugs, such as anticholinesterase inhibitors (tacrine, donepezil) as well as novel nicotinic analogues (ABT-418). Despite these promising results, more research is needed on alternative pharmacological treatments for the treatment of ADHD.

Antidepressive Agents, Tricyclic↗

A family study of psychiatric comorbidity in girls and boys with attention-deficit/hyperactivity disorder.

BACKGROUND: Because attention-deficit/hyperactivity disorder (ADHD) is relatively infrequent among girls, little is known about the nature and causes of psychiatric comorbidity in girls and the reason for gender differences in the prevalence of these comorbidities. METHODS: Using blinded, structured psychiatric interviews, we studied two groups of boys: 140 ADHD probands and 120 non-ADHD comparisons. These groups had 454 and 368 first-degree biological relatives, respectively. We also studied two groups of girls: 140 ADHD probands and 122 non-ADHD comparisons. These groups had 417 and 369 first-degree biological relatives, respectively. RESULTS: The co-occurrence of ADHD and comorbid psychopathology in families was the same for families ascertained through boy and girl probands. CONCLUSIONS: Our results suggest that boys and girls do not differ in the familial risk factors that mediate comorbid psychopathology and the familial aggregation of comorbid disorders in ADHD families. Although this is consistent with prior work suggesting more similarities than differences in the nature of psychiatric comorbidity in ADHD boys and girls, we cannot make strong conclusions, owing to the possibility of cohort effects.

Adolescent↗

Monarch larvae sensitivity to Bacillus thuringiensis- purified proteins and pollen.

Laboratory tests were conducted to establish the relative toxicity of Bacillus thuringiensis (Bt) toxins and pollen from Bt corn to monarch larvae. Toxins tested included Cry1Ab, Cry1Ac, Cry9C, and Cry1F. Three methods were used: (i) purified toxins incorporated into artificial diet, (ii) pollen collected from Bt corn hybrids applied directly to milkweed leaf discs, and (iii) Bt pollen contaminated with corn tassel material applied directly to milkweed leaf discs. Bioassays of purified Bt toxins indicate that Cry9C and Cry1F proteins are relatively nontoxic to monarch first instars, whereas first instars are sensitive to Cry1Ab and Cry1Ac proteins. Older instars were 12 to 23 times less susceptible to Cry1Ab toxin compared with first instars. Pollen bioassays suggest that pollen contaminants, an artifact of pollen processing, can dramatically influence larval survival and weight gains and produce spurious results. The only transgenic corn pollen that consistently affected monarch larvae was from Cry1Ab event 176 hybrids, currently <2% corn planted and for which re-registration has not been applied. Results from the other types of Bt corn suggest that pollen from the Cry1Ab (events Bt11 and Mon810) and Cry1F, and experimental Cry9C hybrids, will have no acute effects on monarch butterfly larvae in field settings.

Animals↗

Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients.

This report of a phase 2 trial of thalidomide (THAL) (200 mg/d; 200 mg increment every 2 weeks to 800 mg) for 169 patients with advanced myeloma (MM) (abnormal cytogenetics (CG), 67%; prior autotransplant, 76%) extends earlier results in 84 patients. A 25% myeloma protein reduction was obtained in 37% of patients (50% reduction in 30% of patients; near-complete or complete remission in 14%) and was more frequent with low plasma cell labeling index (PCLI) (below 0.5%) and normal CG. Two-year event-free and overall survival rates were 20% +/- 6% and 48% +/- 6%, respectively, and these were superior with normal CG, PCLI of less than 0.5%, and beta(2)-microglobulin of 3 mg/L. Response rates were higher and survival was longer especially in high-risk patients given more than 42 g THAL in 3 months (median cumulative dose) (landmark analysis); this supports a THAL dose-response effect in advanced MM.

Angiogenesis Inhibitors↗

Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: We report on a controlled trial of a mixed amphetamine salts compound (Adderall, dextroamphetamine sulfate, dextro-, levoamphetamine sulfate, dextroamphetamine aspartate, levoamphetamine aspartate, and dextroamphetamine saccharate) in the treatment of adult attention-deficit/hyperactivity disorder (ADHD). METHODS: This was a 7-week, randomized, double-blind, placebo-controlled, crossover study of Adderall in 27 well-characterized adults satisfying full DSM-IV criteria for ADHD of childhood onset and persistent symptoms into adulthood. Medication was titrated up to 30 mg twice a day. Outcome measures included the ADHD Rating Scale and the Clinical Global Impression Score. Comorbid psychiatric disorders were assessed to test for potential effects on treatment outcome. RESULTS: Treatment with Adderall at an average oral dose of 54 mg (administered in 2 daily doses) was effective and well tolerated. Drug-specific improvement in ADHD symptoms was highly significant overall (42% decrease on the ADHD Rating Scale, P<.001), and sufficiently robust to be detectable in a parallel groups comparison restricted to the first 3 weeks of the protocol (P<.001). The percentage of subjects who improved (reduction in the ADHD rating scale of > or =30%) was significantly higher with Adderall treatment than with a placebo (70% vs 7%; P =.001). CONCLUSIONS: Adderall was effective and well tolerated in the short-term treatment of adults with ADHD. More work is needed to evaluate the long-term effects of Adderall, or other amphetamine compounds, in the treatment of adults with ADHD.

Adult↗

Thalidomide in the management of multiple myeloma.

Thalidomide has recently been shown to have significant activity in refractory multiple myeloma (MM). A follow-up of the original phase II trial, expanded to 169 patients, shows 2-year survival of 60%; patients receiving > or =42 g over 3 months had a higher response rate and superior survival than those receiving lower doses. The addition of thalidomide to dexamethasone and chemotherapy for the management of post-transplant relapses results in higher response rates. The early results of the Total Therapy II trial for newly diagnosed MM patients show an unprecedented complete remission (CR) and near-CR rate of 69% after two melphalan-based transplants (whether or not receiving thalidomide). In addition, available clinical trial information involving at least 20 patients confirms that thalidomide is active in one third of patients in single-agent trials for refractory disease, with response rates increasing to 50% to 60% in combination with dexamethasone and to as high as 80% in combination with dexamethasone and chemotherapy. When applied as primary therapy in smoldering myeloma, one third of patients experienced 50% paraprotein reduction (PPR); in combination with dexamethasone pulsing, 70% to 80% of symptomatic patients responded. Thus, thalidomide is a major new tool in the treatment armamentarium of MM. The virtual lack of myelosuppression makes it an ideal agent for combination with cytotoxic chemotherapy. Newer, more potent, and less toxic derivatives of thalidomide are being evaluated.

Angiogenesis Inhibitors↗

An open-label, dose-ranging study of atomoxetine in children with attention deficit hyperactivity disorder.

OBJECTIVE: The goal of this study was to evaluate the tolerability and effectiveness of the experimental, noradrenergic specific reuptake inhibitor atomoxetine in the treatment of children with attention deficit hyperactivity disorder (ADHD). METHODS: This was an open, prospective, dose-ranging study of atomoxetine monotherapy in the treatment of 30 children with ADHD between the ages of 7 and 14 years. Atomoxetine was started at 10-20 mg/day and titrated weekly up to 90 mg over 11 weeks, depending on response and adverse effects. Twenty-two children completed the full 11 weeks. We assessed efficacy with weekly clinician and parent ratings of ADHD and oppositional symptoms and monitored adverse effects, laboratory findings, and cardiovascular parameters. RESULTS: Treatment with atomoxetine (mean final, total daily dose of 1.9 mg/kg/day) was very well tolerated without meaningful adverse effects. Atomoxetine significantly reduced core symptoms of ADHD (ADHD-Rating Scale-IV; 38.6% decrease vs. baseline, p < 0.001) with significant improvement (p < 0.05) in all but 1 of the 18 individual items in the ADHD-Rating Scale-IV. More than 75% of subjects who completed 10 weeks of treatment showed > 25% decrease in ADHD symptoms. CONCLUSIONS: These findings extend to children the positive results previously reported in adults diagnosed with ADHD who were treated with atomoxetine. These results support additional controlled trials of atomoxetine in cases of pediatric ADHD.

Adolescent↗

General case quasi-pyramidal staff training to promote generalization of teaching skills in supervisory and direct-care staff.

The authors employed staff training strategies designed to enhance generalization of teaching skills in staff working with persons with developmental disabilities. Staff training consultants initially employed a general case training approach involving the use of specially selected client program exemplars to provide three supervisory staff with generalized teaching skills. Subsequently, supervisory staff used the general case approach to train teaching skills to direct-care staff, with staff training support from the consultants (quasi-pyramidal training). Supervisors showed improvement in teaching skills after supervisory staff training, but only one of the three supervisors exceeded 70% correct skill use. After participating in the training of their own staff, however, supervisors demonstrated further improvements in skill use. All direct-care staff showed improvement after quasi-pyramidal training, with seven of the nine staff exceeding 70% correct skill use. General case quasi-pyramidal training appears to have potential as a strategy for promoting generalization of staff teaching skills in both trainees and trainers.

Activities of Daily Living↗

Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study.

OBJECTIVE: Atomoxetine is an investigational, nonstimulant pharmacotherapy being studied as potential treatment for attention-deficit/hyperactivity disorder (ADHD). It is thought to act via blockade of the presynaptic norepinephrine transporter in the brain. We assessed the efficacy of 3 doses of atomoxetine compared with placebo in children and adolescents with ADHD. METHODS: A total of 297 children and adolescents who were 8 to 18 years of age and had ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, were randomized to placebo or atomoxetine dosed on a weight-adjusted basis at 0.5 mg/kg/day, 1.2 mg/kg/day, or 1.8 mg/kg/day for an 8-week period. ADHD symptoms, affective symptoms, and social and family functioning were assessed using parent and investigator rating scales. RESULTS: Approximately 71% of children enrolled were male, approximately 67% met criteria for mixed subtype (both inattentive and hyperactive/impulsive symptoms), and the only common psychiatric comorbidity was oppositional defiant disorder (approximately 38% of the sample). At baseline, symptom severity was rated as moderate to severe for most children. At endpoint, atomoxetine 1.2 mg/kg/day and 1.8 mg/kg/day were consistently associated with superior outcomes in ADHD symptoms compared with placebo and were not different from each other. The dose of 0.5 mg/kg/day was associated with intermediate efficacy between placebo and the 2 higher doses, suggesting a graded dose-response. Social and family functioning also were improved in the atomoxetine groups compared with placebo with statistically significant improvements in measures of children's ability to meet psychosocial role expectations and parental impact. Discontinuations as a result of adverse events were <5% for all groups. CONCLUSION: Among children and adolescents aged 8 to 18, atomoxetine was superior to placebo in reducing ADHD symptoms and in improving social and family functioning symptoms. Atomoxetine was associated with a graded dose-response, and 1.2 mg/kg/day seems to be as effective as 1.8 mg/kg/day and is likely to be the appropriate initial target dose for most patients. Treatment with atomoxetine was safe and well tolerated.

Adolescent↗

Analysis of pain behavior profiles and functional disability in outpatient physical therapy clinics.

STUDY DESIGN: Descriptive, ex post facto. OBJECTIVES: To determine the proportion of physical therapy outpatients with pain who exhibit various pain behavior profiles, and to determine whether there are differences in functional disability across the profiles. BACKGROUND: Physical therapists treat many patients who have chronic pain. Research suggests that early identification and multidisciplinary treatment are effective and economical for these patients. The Multidimensional Pain Inventory (MPI) and the Pain Disability Index (PDI) are potential screening tools that could be used in physical therapy clinics to determine which patients should be referred for multidisciplinary treatment. METHODS AND MEASURES: MPI and PDI data were gathered on 57 physical therapy outpatients (mean age 44.3 +/- 14.5 years, 22 men and 35 women) with pain of 3 or more months duration. ANOVA was used to analyze differences in mean PDI scores across the MPI profiles. RESULTS: Of all patients, 42.1% fit the Adaptive Coper profile, 29.8% fit the Interpersonally Distressed profile, and 28.1% fit the Dysfunctional profile. There were significant differences in PDI scores among profile groups. Post hoc analysis showed that the PDI scores of the Adaptive Coper and Interpersonally Distressed groups were different from the Dysfunctional group, but that there was no difference between the Adaptive Coper and Interpersonally Distressed groups. CONCLUSIONS: Many patients in outpatient physical therapy settings exhibit behavioral, affective, and cognitive characteristics associated with chronic pain. Thirty-three patients (57.9%) had MPI profiles (interpersonally distressed and dysfunctional) that suggest they might benefit from multidisciplinary treatment.

Adult↗