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Biomedical subjects

L A Rosenberg

Publications and source records attributed to L A Rosenberg.

At least 19 recordsLinked to original sources

Temporary and partial inhibition of platelets by SM-20302 prevents coronary artery thrombosis in a chronic canine model.

We proposed that temporary and partial platelet inhibition by a GPIIb/IIIa receptor antagonist, SM-20302, would provide sustained antithrombotic efficacy in a chronic model of coronary artery thrombosis. Instrumented, conscious dogs received vehicle (Group I, n = 7), low dose SM-20302 (30 microg/kg bolus + 1 microg/kg/min infusion for 6 h) (Group II, n = 7), or high dose SM-20302 (100 microg/kg bolus + 1 microg/kg/min infusion for 6 h) (Group III, n = 7). Thrombosis was initiated by electrolytic injury to the circumflex coronary artery. Coronary blood flow was monitored for 6 h on day 1 and days 2-6. Platelet aggregation was performed in platelet-rich plasma prepared from citrated or heparinized blood. At 6 h, both doses of SM-20302 inhibited adenosine diphosphate-induced platelet aggregation completely (> 90%) in citrated platelet-rich plasma, but incompletely (57-59%) in heparinized platelet-rich plasma. Platelet reactivity returned to baseline values at 24 h. Control animals developed thrombotic occlusion on Day 1. Both doses of SM-20302 maintained vessel patency during the infusion period (Day 1) and the subsequent 5 days. Myocardial infarct size and mortality in the drug treated groups were reduced compared to the vehicle group. Thus, temporary inhibition of platelet reactivity by SM-20302 is associated with sustained prevention of primary thrombus formation, and reduction in infarct size and mortality.

Animals↗

Children's behavioral response to residential treatment.

This study examined behavior changes demonstrated over time by children who had been placed in a residential treatment center. Objective observation of behavior during such a placement is essential for continued treatment planning, including continuing in residence, transfer, or discharge. Teachers and residential treatment counselors completed Child Behavior Checklists at admission, discharge, and time points in between, for 36 patients. The results indicated excellent interjudge reliability for externalizing behavior but not for internalizing. Children who demonstrated oppositional, defiant, or generally conduct-type symptoms seemed to do most poorly in the residential treatment setting. The results suggested that the current design of residential treatment centers may not be effective in dealing with acting-out behavior problems.

Child↗

Behavioral problems and severity of tics.

This study examined the incidence of behavioral symptoms in youngsters with tic disorders. A total of 186 patients were studied using the Child Behavior Checklist and a Motor/Vocal Tic Severity Scale. The relationship between tic severity and the frequency of behavioral symptoms was found to be not simply linear, but influenced by the presence of patients without significant behavioral problems in spite of severe tics (resilient patients) and patients with very negative adjustment although their tic disorder was mild (vulnerable patients). Behavioral problems were not related to age. Patients who were receiving medication showed behavioral problems of different severity from those who were not receiving such agents; this result emphasizes the need for future studies to consider carefully the effects of medication.

Adolescent↗

Cross-cultural studies with the Conners rating scales.

The teacher and parent forms of the Conners Rating Scales were completed by the parents and teachers of 863 children who were living in an area of Bombay, India. Two socioeconomic strata were sampled. The results were compared to American norms for ratings done by parents and teachers. The teacher ratings demonstrated some clear differences from American norms. Correlational analysis suggested that the Conners scales showed greater overlap, and, hence, less independence, than has been reported in the American research literature.

Child↗

The treatment of attention-deficit hyperactivity disorder in Tourette's syndrome: a double-blind placebo-controlled study with clonidine and desipramine.

OBJECTIVES: Because psychostimulants can exacerbate preexisting motor/phonic tics in individuals with Tourette's syndrome (TS), a clinical trial was performed to examine the ability of clonidine and desipramine to modify attention-deficit hyperactivity disorder (ADHD) behaviors in children with TS + ADHD. METHODS: A double-blind, placebo-controlled protocol was used in which each subject served as his or her own control and received, in a randomly assigned fashion, 6-week medication cycles with clonidine (0.05 mg four times daily), desipramine (25 mg four times daily), and placebo. RESULTS: Thirty-seven children with TS+ADHD between the ages 7 to 13 years and of normal intellect were recruited, and 34 (31 males, 3 females) completed the entire protocol. Outcome measures for ADHD included Parent and Teacher Child Behavior Checklists (CBCL), continuous performance tests, and neuropsychologic tests of executive function. Several markers for ADHD were shown to improve significantly (P < .05) after treatment with desipramine (parent linear analogue rating, parent CBCL "hyperactivity" subscale, and teacher CBCL subscales "nervous/overactive," "anxious," and "unpopular"). Improvement with desipramine was always superior to that noted with clonidine. Clinical improvement did not correlate with drug blood levels. On measures of tic severity, neither drug made tics worse. Desipramine showed a statistically significant improvement on a global linear analogue scale, but not on the Hopkins Motor/Vocal Tic Severity Scale, the Tourette Syndrome Severity Scale, or the Yale Global Tic Severity Scale. Clonidine did not significantly alter tic severity on any measure. CONCLUSION: The results of this study suggest that desipramine may be a useful alternative for the treatment of symptoms of ADHD in children with TS.

Adolescent↗

Self-reporting of behavior problems in patients with tic disorders.

Self-awareness of behavioral or emotional problems was examined in 25 children and adolescents with tic disorders by comparing the Youth, Parent, and Teacher forms of the Child Behavior Checklist. In general, their parents reported a significant number of deviant behaviors which were denied by the patients.

Adult↗

Transcriptional and posttranscriptional regulation of inhibin alpha-subunit gene expression in rat Sertoli cells by 8-bromo-3',5'-cyclic-adenosine monophosphate.

FSH is a major regulator of inhibin production in the testis. FSH effects on Sertoli cell inhibin production are believed to be mediated, at least in part, via the cAMP second messenger system. Previously, it has been shown that 8-bromo-cAMP (8-Br-cAMP) stimulates inhibin-alpha mRNA levels. This study examines whether the cAMP-induced increase in inhibin-alpha mRNA levels results from increased alpha mRNA synthesis, decreased degradation of mRNA, or both. The effects of cAMP on inhibin-alpha gene transcription were examined using nuclear run-on assays. Furthermore, the ability of 8-Br-cAMP to drive the transcription of chimeric constructs containing a 2.2-kilobase (kb) segment of the 5'-regulatory region of the alpha gene placed upstream of the coding region of the luciferase reporter gene was also examined. Data from nuclear run-on assays demonstrated rapid induction of alpha gene transcription by cAMP within 2 h and maximal 4- to 5-fold increase within 4-8 h in primary Sertoli cells. Transfection of TM.4 and JEG.3 cells with an alpha (2.2 kb):luciferase chimeric construct (containing 2.2 kb of the alpha gene 5'-flanking DNA) revealed rapid time-dependent induction of luciferase activity by 8-Br-cAMP in these cell types. To examine the effects of 8-Br-cAMP on alpha mRNA stability, cells were pretreated with medium or 50 micrograms/ml 8-Br-cAMP for 24 h before addition of 5 microM actinomycin D to arrest new RNA synthesis, and the decay of alpha mRNA transcripts was assessed over 24 h by Northern analysis and nonlinear regression.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

Transcriptional regulation of inhibin beta B messenger ribonucleic acid levels in TM.4 or primary rat Sertoli cells by 8-bromo-cyclic adenosine monophosphate.

FSH, a major regulator of inhibin production in the testis, is believed to exert its effects via cAMP second messenger system. Inhibin alpha-subunit gene appears to be regulated by cAMP and has a palindromic cAMP response element sequence TGACGTCA. However, the regulation of the inhibin beta B-subunit gene by cAMP has been less clear. It has been assumed that beta B may not be regulated by cAMP, based mainly on observations that FSH stimulates only alpha, not beta B, mRNA levels, and that the 5'-up-stream regulatory region of the beta B gene does not contain the classical cAMP response element. However, we have observed that 8-bromo-cAMP stimulates beta B mRNA levels in both primary Sertoli (approximately 2-fold) and TM.4 cells (approximately 5-fold). We examined whether this cAMP-induced increase in beta B mRNA levels is the result of increased transcription or altered mRNA stability. Data from nuclear run-on assays demonstrate about a 2-fold increase in relative mRNA synthesis rates in primary Sertoli-cells and about a 4- to 5-fold increase in TM.4 cells. Transfection studies in TM.4 and JEG.3 cell lines with beta B:luciferase chimeric reporter gene constructs containing 1.5 kilobases of the beta B 5'-up-stream regulatory region revealed marked cAMP induction of reporter gene activity in both cell types.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

Aseptic meningitis in infants younger than 2 years of age: acute illness and neurologic complications.

OBJECTIVE: We report the clinical features and cerebrospinal fluid (CSF) laboratory values for 277 children younger than 24 months of age with aseptic meningitis who were prospectively evaluated at three Baltimore hospitals between July 1986 and December 1990. A major objective was to define the incidence, etiology, and outcome of neurologic complications occurring during the acute illness. METHODS: Cases were identified by surveillance in the ambulatory care departments of each of the three hospitals, pertinent historical and clinical data were obtained by interview of the parents and by review of the medical records, initial CSF laboratory values were recorded, and appropriate specimens were submitted to determine the viral etiology. A subset of 216 children who participated in a long-term natural history study were followed periodically with neurologic examinations and formal neurodevelopmental testing. RESULTS: Most cases occurred in very young infants; 63.5% of patients were 8 weeks of age or younger, and 84.1% were younger than 16 weeks of age. In this very young cohort, the dominant symptoms were fever and irritability; only 8.7% had evidence of meningeal irritation at the initial examination. The acute illness was complicated by either complex seizures, physical evidence of increased intracranial pressure, or coma in 25 (9.0%) cases. Within the age group under study, these complications were each significantly more likely to occur in patients older than 12 weeks of age than in younger infants. The risk of neurologic complications was similar among infants infected with group B coxsackieviruses and echoviruses, the two major enterovirus classes observed to cause disease. Acute central nervous system (CNS) complications could not be correlated with extremely abnormal CSF laboratory indices. Importantly, there was no risk of long-term neurologic sequelae attributable to acute CNS complications. CONCLUSIONS: While approximately 9% of infants and children younger than 2 years of age with aseptic meningitis experience acute CNS complications in the form of complex seizures, increased intracranial pressure, or coma, the prognosis for long-term cognitive development appears to be as favorable as the prognosis for children with aseptic meningitis who do not experience these complications.

Acute Disease↗

The validity of instruments measuring tic severity in Tourette's syndrome.

By using four different scales that measure tic severity in Tourette's syndrome, three independent judges concurrently evaluated their validity and interjudge reliability in 20 affected individuals. The Yale Global Tic Severity Scale, Tourette's Syndrome Severity Scale, Tourette's Syndrome-Clinical Global Impression Scale, and the Hopkins Motor and Vocal Tic Scale were equally effective in determining overall severity and showed good interrater reliability. Both historical information and direct observation of the subject were shown to have a significant contribution towards the overall assessment of tic severity. With all instruments, tic symptom ratings were shown to be independent of those for either attention-deficit hyperactivity disorder or obsessive-compulsive disorder. A 67% incidence of behavioral problems and social difficulties was identified by the Child Behavior Checklist. Nevertheless, associations with tic severity were limited to areas showing interference with social relationships and school adjustments. These results extend the understanding of Tourette's syndrome severity scales and provide additional information necessary for the development of a unified rating scale.

Adolescent↗

Munchausen syndrome by proxy.

This study examined the indicators of possible presence of Munchausen Syndrome by Proxy (MSBP) in pediatric inpatients discharged against-medical-advice (AMA), in cases transferred to another hospital, and in regular discharges. In a two-year period, there were fourteen AMA discharges and twenty-four transfer cases. These were compared to a randomly selected sample of forty-one regular discharges occurring during the same time period, matched for age, sex and pediatric service. The records were scored for the presence or absence of six MSBP characteristics, which had been developed from a review of MSBP literature. The findings indicated a suspicion for MSBP in 64 percent of the AMA cases, 8 percent of the transfer cases, and none in regular discharges. The findings suggest that AMA discharges need to be examined for the possible presence of MSBP.

Depressive Disorder↗

Protein Synthesis during Natural and Precocious Soybean Seed (Glycine max [L.] Merr.) Maturation.

Protein synthesis was studied during precocious and natural soybean seed (Glycine max [L.] Merr.) maturation. Developing seeds harvested 35 days after flowering were precociously matured through controlled dehydration. Total soluble proteins and proteins labeled with [(35)S]methionine were extracted from control, developing seeds and from precociously and naturally matured seeds and were analyzed by one-dimensional PAGE and fluorography. The results demonstrated that several polypeptides which were designated "mature polypeptides," were synthesized de novo during precocious and natural seed maturation. Two of these polypeptides, 31 and 128 kilodalton in mass, also stained intensely with Coomassie blue, suggesting their abundant accumulation during seed maturation. Results from in vitro translation experiments showed that the mRNAs corresponding to these "maturation polypeptides" accumulated during precocious maturation and in naturally matured seeds, but not in seeds freshly harvested 35 days after flowering (control). The role of the "maturation polypeptides" is currently unknown; however, their presence and that of their corresponding mRNAs was coincident with the ability of matured seeds to establish seedling growth. This study has demonstrated that precocious seed maturation treatments may be extremely useful for investigations of metabolic events and molecular control mechanisms affecting soybean seed maturation.

Journal Article↗