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Biomedical subjects

M Lerner

Publications and source records attributed to M Lerner.

At least 37 records · Page 2Linked to original sources

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↗

Analog classroom assessment of Adderall in children with ADHD.

OBJECTIVE: This was a randomized, double-blind, crossover study of 30 children with attention-deficit/hyperactivity disorder (ADHD) that evaluated the time course effects of four doses of Adderall (5, 10, 15, and 20 mg), an inactive control (placebo), and a positive control (clinical dose of methylphenidate). METHOD: For each treatment condition, a capsule was administered in the morning and assessments were performed in an analog classroom setting every 1.5 hours across the day. Subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measures were obtained for each classroom session, and these measures were used to evaluate time-response and dose response effects of Adderall. RESULTS: For doses of Adderall greater than 5 mg, significant time course effects were observed. Rapid improvements on teacher ratings and math performance were observed by 1.5 hours after administration, and these effects dissipated by the end of the day. The specific pattern of time course effects depended on dose: the time of peak effects and the duration of action increased with dose of Adderall. CONCLUSIONS: This documentation of efficacy in a controlled study supports the addition of Adderall to the armamentarium of psychotropic medications for the treatment of ADHD. The differences in time-response patterns of Adderall and methylphenidate may help tailor treatment to meet specific clinical needs of different children with ADHD.

Adolescent↗

Cytotoxic effects by microinjection of ADP-ribosylated skeletal muscle G-actin in PtK2 cells in the absence of Clostridium perfringens iota toxin.

The ADP-ribosylating toxins Clostridium botulinum C2 toxin and C. perfringens iota toxin, which ADP-ribosylate monomeric G-actin at Arg-177 but not the polymeric F-actin, induce depolymerization of the actin cytoskeleton in cultured cells. Since ADP-ribosylated G-actin has properties of a barbed-end-capping protein, we studied whether the ADP-ribosylated actin affects the actin cytoskeleton of PtK2 cells even in the absence of ADP-ribosylating toxin. Skeletal muscle actin was ADP-ribosylated by C. perfringens iota toxin and the toxin was removed using an anti-iota toxin antibody. Microinjection of ADP-ribosylated actin caused retraction of the cell body, redistribution and depolymerization of the actin cytoskeleton in a concentration- and time-dependent manner. The finding that ADP-ribosylated actin affects per se the actin cytoskeleton explains the cytopathic effects of ADP-ribosylating toxins on microfilaments, although F-actin is not directly modified by the toxins.

ADP Ribose Transferases↗

Perceptions of social pathology in the neighborhood and the etiology of narcotic addiction. A retrospective study.

In this study, we examined whether differential perceptions of poor urban neighborhoods may contribute to narcotic addiction in individuals who grow up in these neighborhoods. Three groups of adult males provided retrospective perceptions of the neighborhoods where they lived at ages 12 to 14. The groups, matched on neighborhood, age, and race, were: narcotic addicts, peer controls--a never-addicted control sample of age-11 associates of the addicts, and community controls--a never-addicted control sample of age-11 peers who did not associate with the addicts. Results suggested clear group differences in perceptions of neighborhood deviance, with addicts perceiving the greatest and community controls the least amount of deviance. However, within groups, subjects who lived in more socially deviant areas, as determined by official records, tended to view their neighborhoods as more deviant than did subjects who lived in less deviant neighborhoods.

Adolescent↗

In vivo spin trapping of nitric oxide generated in the small intestine, liver, and kidney during the development of endotoxemia: a time-course study.

Spin trapping of nitric oxide (NO.) in vivo in liver, small intestine, kidney, and plasma of intact rats was accomplished using diethyldithiocarbamate (DETC) administered intraperitoneally. DETC combines with Fe2+ to form (DETC)2-Fe and is an excellent trapping agent for nitric oxide. DETC distribution and uptake by the organs of interest was determined and the formation of the active trapping agent (DETC)2-Fe was assayed in the various organs and plasma. The capacity of this spin trap to capture NO. in vivo was demonstrated by administering sodium nitroprusside to the animals. The trapping procedure was then used to assess the course of NO. generation during a 6 h period in animals that had been treated with endotoxin. The rate of NO. generation/gram tissue was determined during the last 15 min of each time period. The results indicate that induction of nitric oxide generation begins earliest in the small intestine, then in the liver, and still later in the kidney and plasma. Nitric oxide production was most intense in the liver and was still increasing at the end of the experiment. Control animals receiving the spin trapping agent showed only little or no evidence of nitric oxide production except for the small intestine. The results show that induction of NO. generation caused by endotoxin begins at different times in different organs.

Animals↗

Changes in locus-of-control attitudes about drug misuse in a self-help group in a methadone maintenance clinic.

Clients of a methadone-maintenance clinic in Brooklyn, New York participating in a clinically-guided self-help (CGSH) program plus standard treatment (methadone maintenance plus individual counseling) demonstrated statistically significant changes in locus-of-control beliefs, from external to internal causation, about personal responsibility for drug misuse. Members of two control groups--one participating in a didactic lecture program plus standard treatment and the other receiving only standard treatment--failed to demonstrate similar changes. This increase in internal locus of control in the CGSH group suggests the potential efficacy of CGSH as a relapse-prevention therapeutic technique.

Acquired Immunodeficiency Syndrome↗

Rejection of a gelatin-impregnated Dacron graft.

Sealing of the synthetic vascular graft is important to solve problems of leakage. The use of a new vascular graft--Dacron impregnated by gelatin--is described. After operation the patient developed a febrile reaction, and in spite of a thorough investigation no septic foci could be identified. It is believed that the fever was immunological in origin.

Aged↗

A protein tyrosine phosphatase expressed within dopaminoceptive neurons of the basal ganglia and related structures.

Immunocytochemical and biochemical studies were conducted to characterize a brain-specific protein tyrosine phosphatase, designated STEP for striatal enriched phosphatase. STEP immunoreactivity was most intense in select regions of the CNS receiving a dopaminergic input, and was localized to cell bodies, dendrites, and axonal processes. Western blot analyses of rat brain homogenates revealed a triplet of polypeptides with relative mobilities (M(r)) of 46 kDa, 37 kDa, and 33 kDa enriched within the striatum. Phase separation of protein homogenates by Triton X-114 extraction indicated that this triplet was enriched in soluble but not membrane fractions. Affinity-purified STEP fusion protein exhibited phosphatase activity while a mutated form of the STEP fusion protein (Cys300Ser) showed no demonstrable phosphatase activity.

Animals↗

Emerging forces in cancer care.

The mainstream of scientific research is moving towards increasing recognition of the limits of conventional therapies and cautious optimism about the potential for new biological therapies. This situation has given rise to a social phenomenon among cancer patients. Today, in many parts of the world, a significant minority has chosen to engage actively in the fight for recovery. This minority searches for an intelligent integration of efficacious conventional therapies and complementary therapies involving personal trials of intensive health promotion. These trials cover nutritional, psychological, and immuno-modulating approaches to supporting general health. It appears that 10% among those patients achieve exceptional results, another 10% fail, and 80% become "healthy" cancer patients. While these experiences raise many interesting clinical, scientific and policy questions, they have provided a growing body of evidence that a great deal can be done with behavioural approaches, not in terms of sweeping cures but possibly for some gains in life extension and certainly for great gains in the human experience of being healed (or "becoming whole" with cancer).

Complementary Therapies↗

Lupus anticoagulant: correlation with magnetic resonance imaging of brain lesions.

Brain magnetic resonance imaging (MRI) was performed in 21 patients with systemic lupus erythematosus (SLE) with and without lupus anticoagulant (LAC), one lupus-like patient and 5 patients with primary antiphospholipid antibody syndrome. Thirteen patients had white matter focal brain lesions on MRI, 10 of whom had LAC (p = 0.03). We found no correlation between these lesions and neurologic manifestations, nor any clinical or serologic indices of activity of SLE. Our MRI lesions were similar to those described in multiple sclerosis and may indicate a similar pathologic process.

Adolescent↗

Association of lupus anticoagulant and anticardiolipin antibodies with thrombosis in patients with systemic lupus erythematosus, primary antiphospholipid syndrome and other disorders.

Lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) have been associated with thrombotic events and recurrent fetal loss. In order to assess the role of LA with the thrombotic tendency in various disease states we evaluated 38 patients with confirmed LA [tissue thromboplastin index (TTI) greater than 1.3; circulating anticoagulant index (CAI) greater than 15], subgrouped as follows: a) LA associated with systemic lupus erythematosus (SLE) (n = 13); b) primary antiphospholipid syndrome (PAPS) (n = 16); and c) LA associated with other disorders (n = 9). Male/female ratio differed between the groups: 0/13, 6/10 and 4/5, respectively. Venous and arterial thrombotic events were more common in the PAPS group (87%) compared with the SLE group (61%) and the other disorders group (22%). Serum ACA antiphospholipid IgG levels by ELISA were increased in the SLE and PAPS patients, but did not differ between the groups (167 +/- 24 vs. 190 +/- 28 mu respectively). Antiphospholipid IgM levels were higher in the SLE group compared with the PAPS group (127 +/- 15 vs. 67 +/- 16 mu). Mean TTI and CAI levels did not differ between the SLE, PAPS and other disorders groups (1.8 +/- 0.19, 2.8 +/- 0.9, 2.0 +/- 0.3 for TTI; 25 +/- 4, 33 +/- 4, 32 +/- 5 for CAI). Likewise TTI, CAI and ACA levels did not differ in patients with or without thrombosis. We conclude that the prevalence of thrombotic manifestations varies among patients with similar serum intensities of LA and levels of ACA, suggesting that other factors may be involved in the pathogenesis of thrombosis in these patients.

Adult↗

Molecular characterization of a protein-tyrosine-phosphatase enriched in striatum.

A cDNA clone encoding a neural-specific putative protein-tyrosine-phosphatase (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) has been isolated from a rat striatal cDNA library. The deduced amino acid sequence predicts a protein of approximately 369 amino acids with a strong homology to other members of the family of protein-tyrosine-phosphatases. In vitro translation produces a protein with an apparent molecular mass of 46 kDa. A potential attachment mechanism to the cytoplasmic membrane is suggested by a myristoylation amino acid-consensus sequence at the N terminus of the protein. RNA analyses of various regions of rat brain reveal a 3-kilobase (kb) and a 4.4-kb mRNA. The 3-kb mRNA is highly enriched within the striatum relative to other brain areas and has been termed a "striatum enriched phosphatase" (STEP). In contrast, the 4.4-kb message is most abundant in the cerebral cortex and rare in the striatum. These two messages appear to be alternatively processed RNA transcripts of a single gene.

Amino Acid Sequence↗

Effects of stimulant medication on learning in children with ADHD.

It is well established that stimulant medication improves classroom manageability and attention in terms of time on task, but does stimulant medication improve learning or long-term academic achievement in children with ADHD? There is no clear evidence that it does, but there are at least two reasons why beneficial effects may be obscured in research studies and clinical practice: (1) Higher-than-optimal doses may be prescribed if behavioral response (rather than cognitive response) is used to titrate the dose, and (2) treatment may be overinclusive if diagnostic groups are targeted in which a significant proportion of cases do not have favorable cognitive responses to medication. This article addresses these two issues and describes a large clinical series of patients who were evaluated using a double-blind medication assessment protocol designed to overcome some of the theoretical deficiencies suggested by these issues.

Achievement↗

Anticardiolipin antibodies in Behçet's disease.

Twenty-six patients with Behçet's disease were studied for serum levels of anticardiolipin (ACL) antibody isotypes IgG and IgM. The frequency of elevated levels of ACL antibody isotype IgM was found to be significantly increased in these patients. This increased frequency, however, did not correlate statistically with a thrombotic tendency, colchicine intake, antinuclear antibodies, or a positive VDRL test.

Adult↗

Nature of the light-induced h efflux and na uptake in cyanobacteria.

We investigated the nature of the light-induced, sodium-dependent acidification of the medium and the uptake of sodium by Synechococcus. The rate of acidification (net H(+) efflux) was strongly and specifically stimulated by sodium. The rates of acidification and sodium uptake were strongly affected by the pH of the medium; the optimal pH for both processes being in the alkaline pH range. Net proton efflux was severely inhibited by inhibitors of adenosine triphosphatase activity, energy transfer, and photosynthetic electron transport, but was not affected by the presence of inorganic carbon (C(i)). Light and C(i) stimulated the uptake of sodium, but the stimulation by C(i) was observed only when C(i) was present at the time sodium was provided. Amiloride, a potent inhibitor of Na(+)/H(+) antiport and Na(+) channels, stimulated the rate of acidification but inhibited the rate of sodium uptake. It is suggested that acidification might stem from the activity of a light dependent proton excreting adenosine triphosphatase, while sodium transport seems to be mediated by both Na(+)/H(+) antiport and Na(+) uniport.

Journal Article↗