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Biomedical subjects

R Browne

Publications and source records attributed to R Browne.

At least 19 recordsLinked to original sources
PubMed2006

Syphilitic periostitis in a newly diagnosed HIV-positive man.

A 36-year-old man presented for an HIV test, which answered positive. He gave a six-week history of headache and fever. His syphilis serology was also positive with a Venereal Disease Research Laboratory (VDRL) titre of 1:32, and positive Treponema pallidum particle agglutination (TPPA) assay and fluorescent treponemal antibody (FTA). When he attended for treatment of the syphilis, he had developed severe pain in both lower limbs. Plain radiographs were normal. An isotope bone scan showed multiple areas of increased uptake, consistent with syphilitic periostitis. Some of these lesions were asymptomatic. He was treated with benzathine penicillin and his pain resolved. The bone scan had normalized after six months. We review the previous literature regarding syphilitic bone pain and periostitis. We discuss the importance of considering syphilis in the differential diagnosis of any sexually active adult presenting with bone pain, and highlight the usefulness of isotope bone scans in clarifying the clinical picture.

Adult↗
PubMed2005

Oxidative stress and endometriosis.

BACKGROUND: Little is known about the aetiology of endometriosis; however, in the presence of oxidative stress, reactive oxygen species might increase growth and adhesion of endometrial cells in the peritoneal cavity, leading to endometriosis and infertility. Within a study investigating persistent organic compounds and endometriosis, the authors evaluated the association between oxidative stress and endometriosis. METHODS: Women aged 18-40 years who were undergoing laparoscopy were contacted to participate in the study (n = 100); 84 were eligible and agreed to be interviewed; 78 provided blood specimens. Four markers of oxidative stress and antioxidant status were measured in serum for 61 women. Multiple imputation of missing data was used to generate values for the missing oxidative stress data. RESULTS: Thirty-two women had visually confirmed endometriosis at laparoscopy while 52 did not, including 22 undergoing tubal ligation and 30 with idiopathic infertility. There was a weak association between thiobarbituric acid-reactive substances (nmol/ml) and endometriosis, after adjusting for age, body mass index, current smoking, hormone use in the past 12 months, gravidity, serum vitamin E, serum estradiol, and total serum lipids (beta = 1.18; 95% CI-0.04, 2.39). CONCLUSIONS: These results suggest that oxidative stress might play a role in the development and progression of endometriosis, which should be evaluated in larger studies.

Adolescent↗
PubMed2004

Oxidative stress and glucose levels in a population-based sample.

OBJECTIVES: To examine the relationship between markers of oxidative status and glucose on a population basis. STUDY DESIGN AND SETTING: We report here on a population-based sample of 1315 women and 981 men, aged 35-79 years, randomly selected from residents of Erie and Niagara Counties in western New York between 1996 and 1999. Thiobarbituric reactive substances (TBARS), erythrocyte glutathione (GSH) and plasma glutathione peroxidase (GSH-Px) were measured as markers of oxidative status. Study sample was categorized by quartiles of glucose, degree of abnormality of fasting glucose, and level of metabolic control in patients with diabetes. RESULTS: Men and women in the uppermost quartiles of glucose had higher levels of TBARS (men: Quartile 4 = 1.55 +/- 0.03, Quartile 1 = 1.36 +/- 0.03, women: 1.49 +/- 0.02, 1.30 +/- 0.02 nmol/ml) and lower levels of GSH (men: Quartile 4 = 1.57 +/- 0.03, Quartile 1 = 1.69 +/- 0.03, women: 1.71 +/- 0.03, 1.97 +/- 0.0 mmol/l packed RBCs). In women, compared with normal fasting glucose, impaired fasting glucose was associated with higher levels of TBARS (1.29 +/- 0.01 vs. 1.84 +/- 0.04 nmol/ml), lower levels of GSH (1.85 +/- 0.02 vs. 1.76 +/- 0.05 mmol/l packed RBCs), and higher GSH-Px activity (618.94 +/- 2.64 vs. 644.77 +/- 8.90 IU/l). In women, abnormal fasting glucose was associated with higher levels of TBARS (1.84 +/- 0.04 nmol/ml), lower levels of GSH (1.68 +/- 0.06 mmol/l packed RBCs), and higher levels of GSH-Px (647.72 +/- 9.87 IU/l) than normal or impaired fasting glucose. In men, abnormal fasting glucose was associated with higher TBARS (1.76 +/- 0.04 vs. 1.37 +/- 0.07 nmol/ml), and lower GSH (1.62 +/- 0.05 vs. 2.78 +/- 0.02 mmol/l packed RBCs), than normal fasting glucose. Poor metabolic control was associated with higher TBARS (men: 2.07 +/- 0.08 vs. 1.33 +/- 0.14 nmol/l, women: 2.02 +/- 0.09 vs. 1.35 +/- 0.18 nmol/l) and GSH-Px activity (men: 654.34 +/- 13.45 vs. 599.86 +/- 24.76, women: 660.61 +/- 13.25 vs. 579.42 +/- 27.42 IU/l). CONCLUSIONS: Glucose levels play a role in determining oxidative status in a population sample. The balance between oxidative and antioxidant processes appears to be sensitive to glucose levels with moderate elevations of glucose affecting the oxidative status.

Aged↗
PubMed2002

Minimal and best linear combination of oxidative stress and antioxidant biomarkers to discriminate cardiovascular disease.

BACKGROUND AND AIM: Free radicals have been implicated in the atherosclerotic process of coronary heart disease (CHD). Well-developed laboratory methods may make available a large number of biomarkers of individual oxidative stress and antioxidant status. Such markers are able to quantify different phases of the oxidative stress and antioxidant status of an individual. However, limited knowledge is available on how to combine these biomarkers to best discriminate between individuals with and without CHD. METHODS AND RESULTS: We evaluated combined discrimination properties of six biomarkers of oxidative stress and antioxidant status, as indicators of CHD, in a cross-sectional random sample of 968 white men and women from Buffalo, New York. Individuals with CHD had significantly higher levels of thiobarbuturic acid reacting substances (TBARS) and uric acid, and significantly lower levels of high-density lipoproteins (HDL) after adjusting for age and gender, when compared to healthy subjects. There were no significant differences in erythrocyte glutathione (GSH), trolox equivalent antioxidant capacity (TEAC), and glutathione peroxidase (GSHPx) levels. TBARS were found to be the best discriminating of the biomarkers when it was individually evaluated. TBARS discriminate 76.2% (95% C.I. 0.66-0.82) of the CHD cases from healthy controls. When combining TBARS, GSH, TEAC, HDL, uric acid and GSHPx, they discriminate 81.5% (95% C.I.: 0.67-0.90) of the area under the curve. CONCLUSIONS: These preliminary findings suggest that the combination of multiple markers of oxidative stress does not greatly improve ability to differentiate between individuals with and without CHD compared to the use of TBARS alone.

Adult↗
PubMed2001

Correlates of markers of oxidative status in the general population.

Oxidative stress has been implicated in the etiology of many chronic diseases, including cardiovascular disease. However, limited information exists on the factors that may influence oxidative status in the general population. In a random sample of the population of two counties in western New York, levels of several markers of oxidative status (i.e., thiobarbituric acid-reactive substances, erythrocyte glutathione, and glutathione peroxidase) were determined. A total of 894 men and 903 women aged 35-79 years were included in the study (1996-1999). In addition, a number of sociodemographic and lifestyle characteristics and cardiovascular disease risk factors were measured. Age, markers of glucose metabolism (e.g., plasma glucose level) and insulin resistance (e.g., serum triglycerides, high density lipoprotein cholesterol, body mass index), and postmenopausal status in women were associated with increased oxidative stress and reduced antioxidant potentials. Oxidative status and antioxidant potentials appear to be significantly associated with a number of major cardiovascular disease risk factors; most of them are linked to abnormalities in glucose and insulin metabolism.

Adult↗
PubMed2001

TBARS and cardiovascular disease in a population-based sample.

BACKGROUND: Oxygen radicals might play a crucial role in the pathogenesis of various diseases, including atherosclerosis. Thiobarbituric acid reaction substances (TBARS), a biomarker of oxidative stress, have been proposed as a summary measure of total circulating oxidation. However, there is no strong indication that circulating levels of TBARS are increased in patients with atherosclerosis. DESIGN: We evaluated the relation between TBARS and cardiovascular disease (CVD) in a cross-sectional random sample of white men and women from Buffalo, New York. METHODS: Logistic regression was used to estimate the risk associated with high levels of TBARS. The area under the ROC curve was used to evaluate the discriminating power of TBARS. RESULTS: After adjusting for age and gender, TBARS levels were significantly higher in those with prevalent CVD (OR= 1.73, 95% CI=1.32-2.38), compared to those without a CVD diagnosis. These OR were almost 50% higher after correcting for measurement error (ME) (OR=1.93, 95% CI=1.07-3.40). The area under the ROC curve was 0.69 (95% CI=0.62-0.77) and when corrected for ME reached 0.80 (95% CI=0.65-0.89). CONCLUSIONS: Our results indicate that elevated levels of TBARS were associated with increase risk of the prevalence of CVD, but this effect was no longer significant after adjusting for glucose.

Adult↗
PubMed2001

The suppressive effect of dietary restriction and weight loss in the obese on the generation of reactive oxygen species by leukocytes, lipid peroxidation, and protein carbonylation.

Increased reactive oxygen species generation by the leukocytes of the obese may be responsible for increased oxidative injury to lipids and proteins and, hence, atherosclerosis. We have investigated whether reactive oxygen species generation by leukocytes and other indexes of oxidative damage in the body fall with short-term dietary restriction and weight loss. Nine nondiabetic obese subjects (body mass index, 32.5-64.4 kg/m(2)), not taking any antioxidants, were put on a 1000-Cal diet. Fasting blood samples were taken at 0, 1, 2, 3, and 4 weeks and at 12 weeks after the cessation of dietary restriction. Blood samples were also obtained at 1 and 2 h after administration of 75 g oral glucose at 0 and 4 weeks. Mononuclear cells (MNC) and polymorphonuclear leukocytes (PMN) were isolated, and reactive oxygen species generation was measured. Plasma concentrations of thiobarbituric acid-reactive species (TBARS), 13-hydroxyoctadecadienoic acid (13-HODE), 9-hydroxyoctadecadienoic acid (9-HODE), carbonylated proteins, o-tyrosine, and m-tyrosine as indexes of oxidative damage to lipids, proteins and amino acids, respectively, were measured. Antioxidant vitamins were measured as indexes of antioxidant reserves. Plasma tumor necrosis factor-alpha concentrations were also measured. Mean weight loss was 2.4 +/- 0.6 kg at week 1, 2.5 +/- 1.7 kg at week 2, 3.9 +/- 0.8 kg at week 3, and 4.5 +/- 2.8 kg at week 4 (P < 0.05). Reactive oxygen species generation by PMN fell from 236.4 +/- 95.8 to 150.9 +/- 69.0, 125.9 +/- 24.3, 96.0 +/- 39.9, and 103.1 +/- 35.7 mV at weeks 1, 2, 3, and 4, respectively (P < 0.001). It increased 3 months after the cessation of dietary restriction to 270.0 +/- 274.3 mV. Reactive oxygen species generation by MNC fell from 187.8 +/- 75.0 to 101.7 +/- 64.5, 86.9 +/- 42.8, 63.8 +/- 14.3, and 75.1 +/- 32.2 mV and increased thereafter to 302.0 +/- 175.5 mV at 1, 2, 3, 4, and 16 weeks, respectively (P < 0.005). Reactive oxygen species generation by PMN and MNC increased in response to glucose; the relative increase was greater at 4 weeks than that at week 0 due to a fall in the basal levels of reactive oxygen species generation. Consistent with the fall in reactive oxygen species generation, there was a reduction in plasma TBARS from 1.68 +/- 0.17 micromol/L at week 0 to 1.47 micromol/L at 4 weeks (P < 0.05). The 13-HODE to linoleic acid ratio fell from a baseline of 100% to 56.4 +/- 36.1% at 4 weeks (P < 0.05), and the 9-HODE to linoleic acid ratio fell from a baseline of 100% to 60.5 +/- 37.7% at 4 weeks (P < 0.05). Carbonylated proteins fell from 1.39 +/- 0.27 microgram/mg protein at week 0 to 1.17 +/- 0.12 microgram/mg protein at week 4 (P < 0.05); o-tyrosine fell from 0.42 +/- 0.03 mmol/mol phenylalanine at week 0 to 0.36 +/- 0.02 mmol/mol phenylalanine at 4 weeks (P < 0.005), and m-tyrosine fell from 0.45 +/- 0.04 mmol/mol phenylalanine at week 0 to 0.40 +/- 0.03 mmol/mol phenylalanine at 4 weeks (P < 0.05). The basal concentrations of TBARS, 9-HODE, 13-HODE, carbonylated proteins, o-tyrosine, and m-tyrosine in the obese were significantly greater than those in normal subjects. On the other hand, tumor necrosis factor-alpha concentrations did not change during this 4-week period, nor was there any change in antioxidant vitamins. This is the first demonstration of 1) an increase in reactive oxygen species-induced damage in lipids, proteins, and amino acids in the obese compared with normal subjects; and 2) a decrease in reactive oxygen species generation by leukocytes and oxidative damage to lipids, proteins, and amino acids after dietary restriction and weight loss in the obese over a short period.

Adult↗
PubMed2000

Long-term clinical and pathological effects of cyclosporin in children with nephrosis.

The clinical course of eight children with minimal change disease (MCNS) who were treated with cyclosporin (CYA) was retrospectively reviewed (group A). Five children had frequently relapsing (FRNS) and three had steroid-resistant (SRNS) primary nephrotic syndrome (PNS). The mean age (+/-SEM) of the patients at the time of initiation of CYA therapy was 8.01+/-1.30 years. Twelve follow-up renal biopsies, obtained from patients in group A, were compared with baseline 3.36+/-0.76 years after the initiation of CYA. Follow-up renal biopsies from group A were compared with another cohort of eight children with PNS who did not receive CYA (group B, controls). In this later group four children had FRNS and four had SRNS, and all had MCNS on the initial renal biopsy. In group B, the time between the initiation of CYA and the last renal biopsy was 4.07+/-0.82 years. All 36 baseline and follow-up renal biopsies, from group A and B, were retrospectively reviewed by the same pathologist who was blinded to the clinical course and therapy. CYA decreased the number of relapses in patients from group A from 5.20+/-1.02 to 1.14+/-0.63 episodes per year (P<0.05). All patients with SRNS went into remission after initiation of CYA. Estimated creatinine clearance before CYA therapy was unchanged at the end of the observation period, 133+/-10 vs. 131+/-8 ml/min per 1.73m2, respectively. One child developed reversible acute renal failure while on CYA therapy. Attempts to wean three patients off CYA after 3.89+/-0.87 years of CYA therapy were unsuccessful. Mild but increasing tubular atrophy and interstitial fibrosis was observed in serial biopsies of 75% of the patients in group A compared with 25% of the patients in group B, all of whom had MCNS on initial biopsy. In addition, the percentage of renal cortex showing interstitial fibrosis and tubular atrophy in biopsies from group A patients was slightly greater than that of the group B patients (P<0.05). Hence, CYA therapy in children with MCNS is associated with mild renal interstitial fibrosis and tubular atrophy similar to that noted in a minority of the patients with primary MCNS who were not treated with CYA. However, the mild chronic interstitial damage is more frequent and extensive in MCNS patients treated with CYA, suggesting drug-related interstitial alteration. Despite its efficacy and minimal nephrotoxicity in most patients with MCNS, CYA therapy carries the potential for significant morbidity.

Atrophy↗
PubMed2000

Effect of triiodothyronine on reactive oxygen species generation by leukocytes, indices of oxidative damage, and antioxidant reserve.

We have examined the effect of short-term triiodothyronine (T3) administration on reactive oxygen species (ROS) generation by leukocytes in 9 euthyroid subjects. At a dose of 60 microg/d orally for 7 days, T3 induced a significant increase in ROS generation by mononuclear cells (MNCs) from 183 +/- 102 mV at baseline to 313 +/- 111 mV on the seventh day (P < .02), and by polymorphonuclear leukocytes (PMNLs) from 195 +/- 94 mV at baseline to 302 +/- 104 mV on the seventh day (P < .02). There was also a significant increase in meta-tyrosine (P < .001) and ortho-tyrosine (P < .001), known indices of oxidative damage to proteins and amino acids. However, there was no increase in plasma thiobarbituric acid-reactive substances (TBARS), an index of oxidative damage to lipids, and in the level of carbonylated proteins, a less sensitive index to assess protein oxidation. There was no decrease in the level of antioxidants such as alpha-tocopherol, vitamin A, beta-carotene, lycopene, and lutein/zeaxanthin. The stimulatory effect on ROS generation may reflect a generalized increase in metabolic activity or may be a specific effect on NADPH oxidase in leukocyte membranes. The absence of a significant change in TBARS, carbonylated proteins, alpha-tocopherol, vitamin A, beta-carotene, lycopene, and lutein/zeaxanthin may reflect the short duration of the increased ROS load.

Adult↗
PubMed2000

Labour and delivery complications at birth and later mania. An Irish case register study.

BACKGROUND: Several reports postulate that manic depression and schizophrenia share environmental risk factors. Although obstetric adversity has been suggested as a risk factor for schizophrenia, few studies have examined its relationship to bipolar affective disorder. AIMS: To assess the rate of obstetric complications incurred by patients with mania compared with controls. METHOD: From the Dublin Psychiatric Case Register we identified individuals with a discharge diagnosis of mania and traced their birth records. Each case was matched with a control of the same gender, born in the same hospital, in the same year, matched for maternal age, parity and social class. Two obstetric complications scales were used to make blind evaluations of labour and delivery data. RESULTS: Patients with mania did not experience a greater frequency or severity of labour and delivery complications than their matched controls. Rates of obstetric adversity were unrelated to the presence or absence of family history of psychiatric disorder. Obstetric adversity was unrelated to the age at first diagnosis. CONCLUSIONS: These findings suggest that obstetric adversity is not a risk factor for later mania.

Bipolar Disorder↗
PubMed2000

Labour and delivery complications and schizophrenia. Case-control study using contemporaneous labour ward records.

BACKGROUND: Controversy continues regarding an association between obstetric complications and risk of schizophrenia in early adult life. AIMS: To compare the rate of labour and delivery complications among persons who developed schizophrenia with controls; to establish whether any complication is associated with later schizophrenia. METHOD: We located the labour ward records of 431 individuals with schizophrenia and of same-gender controls from the same hospital birth series. Mothers were matched by age, socio-economic group and parity. Individual complications were evaluated blindly using two obstetric complication scales. RESULTS: Overall, the rate of labour and delivery complications for those who developed schizophrenia did not differ from that of controls. Males who had presented to psychiatric services before the age of 30 had a greater frequency of and more severe labour/delivery complications than their matched controls. CONCLUSIONS: Other than among young-onset males we found no increase in labour and delivery complications among cases.

Case-Control Studies↗
PubMed1998

Premature peripheral vascular disease: clinical profile and abnormal lipid peroxidation.

The aim of this study was to determine any biochemical differences between early-onset peripheral vascular disease and typical onset atherosclerosis, and age-matched controls. A subset of patients present at a young age ( < 50 years) with peripheral vascular disease which pursues an aggressive course. As lipid oxidation seems important in atherosclerosis, total lipid peroxides, oxidized subfractions, and Trolox equivalent antioxidant capacity (TEAC) were studied in patients with premature peripheral vascular disease. Charts were reviewed of patients operated on for vascular occlusive disease over a 5-year period. Patients with early-onset peripheral vascular disease (group I) were evaluated for biochemical abnormalities and compared with typical onset atherosclerotics (group II) and age-matched controls (group III). Sixteen patients with early-onset peripheral vascular disease underwent biochemical evaluation. Conventional lipid profiles did not differ statistically from those of age-matched controls, except for mild elevations in LDL and VLDL in patients with vascular occlusive disease (207 and 195 mg/dl in groups I and 11 versus 157 mg/dl in group III). Total oxidative potential was significantly elevated (P = 0.006) 3.04, 2.15 and 2.04 nmol/ml in groups I, II and III, respectively. Levels of oxidized LDL and VLDL were even more significantly elevated (P = 0.0009) for premature peripheral vascular disease, (1.2, 0.58 and 0.47 nmol/ml in groups I-II). TEAC values did not differ significantly between groups (0.83, 0.82, 0.82 nmol/ml) and did not correlate with total lipid peroxide values for individual patients. In conclusion, lipid peroxides were significantly elevated in patients with premature peripheral vascular disease, the most marked changes being seen in oxidized LDL and VLDL subfractions. Lipid peroxides were elevated when standard lipid profiles were only mildly abnormal. The poor long-term prognosis in these patients suggests the need for aggressive evaluation and treatment of lipid abnormalities.

Adult↗
PubMed1998

Lipid hydroperoxide stimulates retinal neovascularization in rabbit retina through expression of tumor necrosis factor-alpha, vascular endothelial growth factor and platelet-derived growth factor.

To test the hypothesis that oxidative damage associated with tissue hypoxia plays a role in neovascularization, a lipid hydroperoxide (LHP) was injected into the vitreous of rabbits. Single injections of LHP (50-600 microg) caused a sustained retinal neovascularization visualized clinically by ophthalmoscopy and confirmed by microscopy. Vasodilators, i.e. histamine and nitric oxide, peaked at 6h and 7 days, respectively. The levels of both tumor necrosis factor-alpha and interleukin-1alpha peaked at 12h and dropped to basal levels by 24h. Expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta peaked at 24h and were sustained throughout the following 3 weeks, and platelet-derived growth factor was also elevated throughout the same period. Upregulation of these five angiogenic cytokines, but not basic fibroblast growth factor, occurred prior to the appearance of neovascularization. Leakage of fluorescein at the tips of new vessels was demonstrated by fluorescein angiography. Linoleic hydroperoxide induced neovascularization, but saturated or unsaturated native C-18 fatty acids had no effect. The cascade of multiple, angiogenic cytokines induced by LHP may interact to promote sustained neovascularization.

Journal Article↗
PubMed1998

Glomerular filtration rate in children following renal transplantation.

Most studies evaluating renal function post-renal transplantation in children have used serum creatinine (S(Cr)) or estimates of its clearance (C(SCH)). When renal function is impaired both S(Cr) and the C(SCH) overestimate glomerular filtration rate (GFR), especially during cyclosporine therapy. This study measured GFR in 64 children (age range: 4-19 years) with stable renal function who received renal allografts at the Childrens Medical Center of Dallas, 31 from live related donors (LRD) and 33 from cadaveric donors (CAD). 125I-iothalamate clearance (C(IO)) was used as the reference standard for measuring GFR. Data from 100 C(IO) studies, were analyzed and results reported as mean +/- S.E.M. C(IO) performed during the first year after renal transplantation in 23 children who received allografts from LRD was 72.4+/-5.5 ml/min per 1.73 m2 compared to 50.4+/-7.4 ml/min per 1.73 m2 in 18 children who received allografts from CAD (p<0.05). Beyond the first year post-renal transplantation there was no difference in C(IO) between LRD and CAD allografts. When S(Cr) was compared to C(IO), the relationship was nonlinear. C(IO) was also compared to the simultaneous estimation of creatinine clearance by C(SCH). The overestimation of GFR by C(SCH) was inversely proportional to the level of renal function. When renal function was normal or mildly reduced (C(IO) > 50 ml/min per 1.73 m2), C(SCH) closely approximated C(IO). When renal function was moderately to severely curtailed (C(IO) < or = 50 ml/min per 1.73 m2), C(SCH) overestimated C(IO) by 43.6+/-5.6%. The study concludes that in children with renal transplant: 1) C(IO) is higher in allografts from LRD compared to CAD kidneys only in the first 12 months following renal transplantation; 2) S(Cr) is a poor predictor of C(IO); and 3) C(SCH) consistently overestimates GFR children following renal transplantation unless renal function is normal or only mildly decreased.

Adolescent↗
PubMed1998

Evaluation of individual subjects in the analog classroom setting: II. Effects of dose of amphetamine (Adderall).

Multiple dependent variables were graphed for 29 subjects who participated in a double-blind evaluation of 4 doses of Adderall, plus positive (methylphenidate) and placebo control conditions. Five judges ranked the conditions for each subject, and analyses of individual subjects indicated that these rankings were concordant (reliable) across judges. Consensus rankings were assigned to each subject, and an analysis of these ranks showed that the conditions differed significantly. The choice of best conditions were judged to be across 3 doses of Adderall (10, 15, and 20 mg). This confirms the clinical impression of individual differences in optimal dose of stimulant medication. The methodological, graphical, and statistical methods presented in this article provide a systematic, reliable procedure for evaluating relative response of individuals to different doses of stimulant medication.

Amphetamine↗
PubMed1998

Objective and subjective measures of the pharmacodynamic effects of Adderall in the treatment of children with ADHD in a controlled laboratory classroom setting.

In a randomized double-blind crossover study of children with attention deficit hyperactivity disorder (ADHD), the time course effects of four doses of Adderall (5, 10, 15, and 20 mg) and an inactive (placebo) control, and an active (Ritalin) control were evaluated. A laboratory classroom setting was established in which subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measurements were taken every 1.5 hours across the day. In addition to significant time and dose effects of Adderall, significant time-of-day effects were documented in the placebo condition for the subjective measure of deportment and objective measures of performance. Regression analyses were used to estimate the magnitude of these baseline effects. Correlations across time were used to evaluate the test-retest reliability of each measure in the face of these time-dependent placebo effects. After placebo/time adjustments, within-subject correlations between pairs of measures were used to evaluate the validity of the math test as a measure of response to stimulant medication.

Adolescent↗