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B Geller

Publications and source records attributed to B Geller.

At least 55 records · Page 3Linked to original sources
PubMed1993

Charged residues render pro-OmpA potential dependent for initiation of membrane translocation.

We have examined the effects of positively and negatively charged residues on the translocation of outer membrane protein A precursor (pro-OmpA) across the bacterial inner membrane. Pro-OmpA does not translocate across the membrane when 2 positively charged residues are inserted immediately after the leader peptide, whereas it does insert when 2 neutral or negatively charged residues are introduced. Using a cell-free translocation system, we show that the membrane potential stimulated the rate of initial insertion of pro-OmpA with negatively charged residues, inhibited pro-OmpA with positively charged residues, and had no effect on neutral pro-OmpA. Thus, acidic residues render pro-OmpA potential-dependent for loop formation, which then initiates the translocation process.

Amino Acid Sequence↗
PubMed1993

Effect of tricyclic antidepressants on switching to mania and on the onset of bipolarity in depressed 6- to 12-year-olds.

The authors present data on the rates of onset of bipolar phenomena, at 2- to 3-year follow-up, in depressed 6- to 12-year olds. The subjects had participated in the nortriptyline drug study. There were high rates of onset of bipolarity and of switching to mania while patients were on tricyclic antidepressants (TCAs). Mania developed only in subjects who had received TCAs at some time in the past or were receiving them concurrent with the onset of mania. These findings were analyzed with respect to the influence of multiple covariates, including family history of manic disorders and pubertal status. The authors discuss the implications of these findings for the prescription of TCAs to children who present with major depressive disorder and have a family history of bipolarity or a history of bipolar symptoms. The relevance of these findings for the later development of rapid cycling is discussed and compared with predictors of rapid cycling in adults.

Antidepressive Agents, Tricyclic↗
PubMed1993

Another sudden death in a child treated with desipramine.

The sudden death of three children receiving the tricyclic antidepressant medication desipramine for behavioral disorders was reported in 1990. We now provide new information about these children and describe a fourth case. Because desipramine is a useful medication for many children, these deaths pose clinical dilemmas for physicians and families. The cardiac long QT syndrome has been proposed as a mechanism for these sudden deaths. Considerable uncertainty remains about the basis of the apparent association between the use of desipramine and the sudden deaths.

Attention Deficit Disorder with Hyperactivity↗
PubMed1993

Genetic studies of affective disorders: should we be starting with childhood onset probands?

OBJECTIVE: The objective of this study is to test whether the presence of childhood onset affective disorder identifies families with increased incidence and severity of affective disorders. METHOD: Family history information was collected on the first and second degree relatives and first cousins age > or = 15 years of 22 children with bipolar affective disorder, 54 children with major depressive disorder, and 31 psychiatrically normal children. RESULTS: Compared with the relatives of normal children, relatives identified through children with bipolar affective disorder or major depressive disorder had elevated rates of affective disorders and increased severity of affective disorders as judged by earlier age of onset and increased suicide attempts. Segregation analyses could reject purely environmental transmission of illness. CONCLUSION: Ascertaining families through childhood onset affective disorder probands identifies extended pedigrees with high incidence and severity of affective disorders. These families may be more appropriate for genetic analyses than are families of adult probands.

Adolescent↗
PubMed1992

Early findings from a pharmacokinetically designed double-blind and placebo-controlled study of lithium for adolescents comorbid with bipolar and substance dependency disorders.

1. This manuscript reports the early findings from a National Institute on Drug Abuse funded study of lithium for adolescents dually diagnosed with bipolar and substance dependency disorders. The authors elected to publish early findings in the hope that it would accomplish a twofold mission. 2. The first part would be to encourage other investigators to participate in research in this area and the second would be to heighten the awareness of clinicians that adolescents presenting with either one of these disorders might also have the other. 3. The early findings demonstrated the feasibility of recruiting, retaining and monitoring this complex population on an outpatient basis. 4. Steady-state serum lithium levels were pharmacokinetically placed in the study range, 0.9-1.3 mEq/L. Preliminary results are encouraging in finding lithium more effective than placebo for alleviating both the substance dependency and the mood disordered symptomatology. 5. The characteristics of the study population to date have been chronicity of both disorders, impairment in the severe range in multiple areas of functioning, and strong family histories for both affective and substance use disorders. The substance dependency was to both alcohol and marijuana; but all subjects also had marked polydrug abuse. 6. In order to best monitor lithium compliance and drug/alcohol use during protocol, randomly timed weekly serum and urine assays were obtained. 7. The implications of these early findings for the outcome of this acute phase study and for the development of longitudinal treatment strategies are discussed.

Adolescent↗
PubMed1992

Pharmacokinetically designed double-blind placebo-controlled study of nortriptyline in 6- to 12-year-olds with major depressive disorder.

A random assignment, double-blind, placebo-controlled study of nortriptyline in 50 prepubertal 6- to 12-year-olds with Research Diagnostic Criteria and DSM-III major depressive disorder was performed. The protocol included a 2-week placebo wash-out phase and an 8-week double-blind, placebo-controlled phase with weekly plasma level monitoring. Active subjects had their plasma level pharmacokinetically placed at 80 +/- 20 ng/ml by using previously developed tables to determine the starting dose from a plasma level 24 hours after a single dose administered at baseline. The mean plasma level was 89.9 ng/ml. The study population was severely depressed, had a chronic, unremitting course of long duration before the study, had a high percentage of family histories with affective disorder, alcoholism and suicidality, and had a high rate of comorbidity. None of the subjects had ever received tricyclic antidepressants before this study. There was a poor rate of response in both treatment groups (30.8% active, 16.7% placebo). Active subjects did not evidence the anticholinergic side effects reported in adult samples. The implications of these findings for future pharmacotherapy studies of depressed children are discussed.

Child↗
PubMed1992

Baseline and 2- to 3-year follow-up characteristics of placebo-washout responders from the nortriptyline study of depressed 6- to 12-year-olds.

Data are presented on the baseline characteristics and 2- to 3-year follow-up assessments of placebo-washout responders (PWRs) from a previously reported pharmacokinetically designed double-blind placebo-controlled trial of nortriptyline for major depressive disorder in 6- to 12-year-olds. Eleven of the 12 PWRs consented to participate in the follow-up study. At baseline, the only significant difference between the PWRs and the non-PWR subjects was that more females were PWRs. Notably, there were no significant differences with respect to severity, chronicity, age of onset, or comorbid psychopathology. The follow-up assessments showed that the rate of relapse to major depressive disorder and the rate of development of bipolarity were not significantly different for PWRs compared with non-PWRs. The authors discuss these findings vis-à-vis the adult literature and provide recommendations for the use of placebo-washout phases in future double-blind, placebo-controlled psychopharmacology trials in children.

Bipolar Disorder↗
PubMed1992

Lithium and tricyclic antidepressants.

Pharmacokinetic studies of lithium and tricyclic antidepressants (TCAs) in children and adolescents report similarities to adults with respect to a wide interindividual genetic variation in the rate of elimination and with regard to the linear nature of the system. Children may eliminate these medications more rapidly; therefore, more frequent dosing may be necessary to maintain steady state serum lithium or plasma TCA levels. Doses of these medications necessary for desired blood levels can be obtained from tables based on nomograms (i.e., one-step dosage adjustment determined from a single serum lithium or plasma TCA level drawn 24 hours after administration of a single dose). Use of these dose prediction tables avoids toxicity due to excessively high blood levels in genetically slow metabolizers in whom medication regimes that use mg/kg dose schedules may produce toxic blood levels.

Adolescent↗
PubMed1991

Psychopharmacology of children and adolescents: pharmacokinetics and relationships of plasma/serum levels to response.

This article reviews data from the literature on pharmacokinetics and on relationships of plasma/serum levels to response in the child and adolescent population. The following topics will be covered: saliva vs. serum monitoring, drug-drug interactions, enzyme induction, and the effect of febrile illnesses on protein binding. Similarity of elimination processes based on manifestations that are genetically determined across age groups will be contrasted to elimination mechanisms that are different for the pediatric group due to age specific developmental considerations. Age related differences in plasma/serum level response relationships will be discussed with respect to study population characteristics and pharmacodynamic implications.

Adolescent↗
PubMed1990

Double-blind placebo-controlled study of nortriptyline in depressed adolescents using a "fixed plasma level" design.

We performed a random assignment, double-blind, placebo-controlled study of nortriptyline (NT) in postpubertal 12- to 17-year-olds with Research Diagnostic Criteria (RDC) and DSM-III major depressive disorder. The protocol included a 2-week placebo washout phase and an 8-week double-blind, placebo-controlled phase with weekly plasma level monitoring. Active subjects had their plasma level placed at 80 +/- 20 ng/ml by using previously developed tables to determine the starting dose from a plasma level drawn 24 hours after a single dose administered at baseline. The study population was severely depressed and had a chronic, unremitting course prior to study; a high percentage of family histories with affective disorder, alcoholism, and suicidality; and a high rate of comorbidity. Of the 52 subjects enrolled, there were 17 placebo washout responders, 4 dropouts, and 31 completers (12 active and 19 placebo). Only one active subject responded; therefore, the study was terminated early. The mean NT plasma level was 91.1 (18.3 SD) ng/ml. The two treatment groups had similar postprotocol severity ratings. Subjects on active drug did not evidence the anticholinergic side effects reported in adult samples. The negative outcome in this study is similar to the findings in our previously reported NT study in prepubertal 6- to 12-year-olds.

Adolescent↗