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Biomedical subjects

E Robins

Publications and source records attributed to E Robins.

At least 37 records · Page 2Linked to original sources
PubMed1985

Cerebrospinal fluid levels of amitriptyline, nortriptyline, imipramine and desmethylimipramine. Relationship to plasma levels and treatment outcome.

Fifty-five (55) depressed patients were treated with amitriptyline (AMI) or imipramine (IMI). Concentrations of AMI, IMI, and their metabolites, nortriptyline (NT) and desmethylimipramine (DMI), were measured in cerebrospinal fluid (CSF) and plasma at steady state by gas chromatography mass spectrometry (GC/MS). Highly significant correlations between CSF and plasma levels of AMI, NT, IMI, and DMI were found (r greater than 0.75; P less than 0.0001 in all cases). There were no significant sex, diagnostic subgroup, or geographic difference in any of the drug parameters measured. An evaluation of the relationship between CSF levels of drug variables and clinical response showed essentially no significant correlations between these various parameters. The results obtained do not support the concept of a 'therapeutic window' for levels of plasma NT in AMI-treated patients. Furthermore, the highly significant correlations between CSF and plasma compartments in terms of drug and metabolite levels would argue against the need to measure CSF levels of these parameters in clinical practice. Plasma level measurements should be equally informative, and simpler to obtain.

Amitriptyline↗
PubMed1985

Effects of amitriptyline and imipramine on brain amine neurotransmitter metabolites in cerebrospinal fluid.

The effects of amitriptyline (AMI) or imipramine (IMI) on levels of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) (the major brain metabolites of the neurotransmitters norepinephrine [NE], serotonin [5-HT], and dopamine [DA]) in cerebrospinal fluid were determined in 66 subjects with unipolar and bipolar depression. There were significant reductions in MHPG and 5-HIAA levels for the depressed group taken as a whole, but levels of HVA did not change significantly. The changes were similar when subjects were grouped as treated with AMI and IMI and with unipolar and bipolar depression. Reductions in MHPG and 5-HIAA levels were greater in women than in men. In all subjects with depression and in those treated with AMI and IMI, amine metabolite changes did not differ significantly between those who had a positive clinical response to drug therapy and those who did not. Responders with bipolar depression had smaller reductions in MHPG levels than did responders with unipolar depression. The similar effects of AMI and IMI on MHPG and 5-HIAA differ from the dissimilar effects of the two drugs on NE and 5-HT amine uptake systems reported in animal and in in vitro studies. Results provide conclusive evidence of the effects of AMI and IMI on noradrenergic and serotonergic (but not dopaminergic) systems in patients with depression.

Adult↗
PubMed1984

Pretreatment DST and hypothalamic-pituitary-adrenocortical function in depressed patients and comparison groups. A multicenter study.

Pretreatment measures of hypothalamic-pituitary-adrenocortical (HYPAC) function in depressed, manic, and healthy normal subjects showed that nonsuppression on the dexamethasone suppression test (DST) had less positive predictive value for major diagnostic category and was more frequent in normals (8/77) than recently reported, although it was yet more frequent in depressed patients (35/111). Nonsuppression was common in manics (8/16), was similar in unipolar and bipolar depressed patients (35% and 27%, respectively), and did not segregate with melancholic, endogenous, or psychotic depression subtypes. Patterns of post-DST plasma cortisol concentration other than simple escape or nonescape from suppression were common. Nonsuppression of 9 AM plasma cortisol levels on the DST had as good or better diagnostic specificity as nonsuppression of any of three post-DST samples. Nonsuppression was not completely synonymous with HYPAC hypersecretion. Means of pre-DST HYPAC measures (morning plasma cortisol, urine free cortisol, and CSF cortisol levels) were elevated in depressed patients compared with normals. There were significant differences in HYPAC measures of depressed patients studied at different centers. Age correlated positively and body weight negatively with plasma cortisol level.

Adult↗
PubMed1984

Pretreatment neurotransmitter metabolite levels and response to tricyclic antidepressant drugs.

Relationships between pretreatment neurotransmitter metabolite levels and response to imipramine and amitriptyline were studied in 104 depressed patients. Normal values for urinary norepinephrine and low values for urinary MHPG were associated with greater incidence of drug response in bipolar, but not unipolar, patients. For unipolar, but not bipolar, patients low CSF 5-HIAA and high urinary metanephrine values were associated with a greater incidence of drug response. These data indicate that the pretreatment functional state of catecholamine and serotonin systems is associated with type of response to drug treatment. The authors present hypotheses about the association of alterations in serotonin and norepinephrine systems and definable subtypes of depression.

Amitriptyline↗
PubMed1983

Human trabecular meshwork in primary culture: a morphological and autoradiographic study.

The growth and behaviour of human trabecular meshwork cells in primary culture was studied by light microscopy, time-lapse cinephotomicrography, autoradiography and electron microscopy. In all 925 explants of trabecular tissue from 132 eyes (68 +/- 14 years) were set up, and 20% produced extensive monolayers. Failure to produce primary outgrowths did not increase substantially until the eyes were over 5 days post-mortem. The latent period prior to growth was anything from a few days to 4 weeks; only then did meshwork cells label with [3H]-thymidine. The cells which grew incorporated large amounts of [3H]-leucine and this served as a useful marker to identify migratory cells. In addition they had the ultrastructural features of metabolically active cells including many mitochondria, a well-developed Golgi apparatus, abundant rough endoplasmic reticulum and prominent lysosomes. It was considered that the cells in primary culture had many features in common with 'activated' rather than normal meshwork cells.

Adult↗
PubMed1983

Ultrastructural and biochemical observations on the effect of 4-hydroxyanisole plus tyrosinase on normal human melanocytes and keratocytes in tissue culture.

Cultures of melanocytes and keratocytes were exposed to 15 micrograms ml-1 tyrosinase and 4-hydroxyanisole (4-OHA) 5 X 10(-4) M to 5 X 10(-2) M for 1 to 24 h. No damage was suffered by either cell below 5 X 10(-3) M 4-OHA for 6 h, but higher concentrations and longer exposures extensively damaged both cells. Exposure of cells washed free of culture medium to tyrosinase and 4-OHA 1 X 10(-3) M for 1 h resulted also in extensive damage. This indicates that an early-formed toxic product of the reaction between tyrosinase and 4-OHA is inactivated by constituents of the medium. This was confirmed by Liquid Chromatography and Scanning Spectrophotometry which showed that a toxic 4-OHA quinone immediately reacted with nucleophilic substances in the medium resulting in products which, on accumulation, are probably responsible for the later (6 h plus) damage to melanocytes and keratocytes. A possible effect of allegedly specific melanocytotoxic drugs on keratocytes should always be borne in mind with tissue culture experiments.

Anisoles↗
PubMed1983

CSF monoamine metabolites in mania.

As part of the National Institute of Mental Health Clinical Research Branch Collaborative Program on the Psychobiology of Depression, the authors compared concentrations of CSF monoamine metabolites (the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol [MHPG], the dopamine metabolite homovanillic acid [HVA], and the serotonin metabolite 5-hydroxyindoleacetic acid [5-HIAA]) from 14 hospitalized manic patients with concentrations from 62 healthy comparison subjects. The manic patients had significantly higher levels of MHPG. Levels of 5-HIAA and HVA did not differ between the manic patients and the comparison male subjects, but they were elevated in the female manic patients. MHPG was the only metabolite that correlated significantly with mania symptom ratings. These data are consistent with findings that have shown abnormal, perhaps excessive, central noradrenergic activity in patients with mania, but not with those suggesting deficits in serotoninergic function.

Adult↗
PubMed1982

Behavioural measurement and drug response characteristics of unipolar and bipolar depression.

This research is part of the NIMH--CRB Collaborative Study on the psychobiology of depression. The main objective of the research programme is to test hypotheses concerning the interaction of neurobiological mechanisms and behaviour in the depressive disorders. Part I of the report describes the rationale and the overall approach to measuring behavioural state and outcome in the research programme. Part II reports on the results of applying the behavioural methods to a comparison of the clinical phenomenology of unipolar and bipolar depression. The behavioural patterns expressed during the episode by the two groups are different. Further, the two types are shown to react differently to treatment with tricyclic drugs, reinforcing the thesis that they are qualitatively distinct forms of the depressive disorders.

Antidepressive Agents, Tricyclic↗
PubMed1982

Pre-treatment neurotransmitter metabolites and response to imipramine or amitriptyline treatment.

Preliminary data are presented from the NIMH Collaborative Study on the psychobiology of depression, biological studies, dealing with relationships between the pre-treatment levels of the neurotransmitter metabolites 3-methoxy-4-hydrophenethyleneglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) and the subsequent therapeutic response of depressed patients to imipramine or amitriptyline. Eighty-seven depressed patients were studied during pre-treatment and treatment periods. It has been found that (1) both low pre-treatment urinary MHPG and low CSF 5-HIAA values are associated with a response to imipramine; these relationships were not artefacts due to sex or age; (2) there were no significant relationships between pre-treatment urinary MHPG, CSF MHPG, 5-HIAA, or HVA values and the subsequent response, or failure of response, to amitriptyline; (3) there was not a bimodal distribution for CSF 5-HIAA. For both males and females, there were positive and statistically significant correlations between CSF MHPG and urinary MHPG; for the females, there were positive and significant correlations between both urinary and CSF MHPG and CSF 5-HIAA. The theoretical and practical implications of these findings are discussed.

Amitriptyline↗
PubMed1982

Drinking patterns in homosexual and heterosexual women.

The lifetime prevalence of heavy and problem drinking was found to be significantly higher in a sample of homosexual women (N = 57) compared to a demographically matched sample of heterosexual women (N = 43). This prevalence of excessive drinking is not explained by personality traits, psychiatric diagnosis, gender identity, history of frequenting gay bars, or family history of alcoholism.

Adolescent↗
PubMed1982

Amitriptyline overdose: clinical effects on tricyclic antidepressant plasma levels.

Tricyclic antidepressant (TCA) plasma levels after amitriptyline overdose were reviewed in a retrospective study. Amount of drug taken correlated with total TCA levels. Plasma concentrations were higher in blacks than whites, but no association could be found between TCA levels and age or sex of patients. History of routine use of amitriptyline at the time of overdose did not predict TCA levels, but the one fatality could be shown on the basis of previous steady-state levels to be a slow metabolizer. Serious overdoses as documented by high plasma TCA levels were seen in all major diagnostic groups.

Adolescent↗
PubMed1981

Human corneal endothelial cell repair in health and disease.

The human corneal endothelium which is exposed to a variety of physical and chemical insults can repair itself either by mitotic division, or by simple expansion and spreading of the neighbouring cells, or through an elaborate DNA repair system. The present study suggests that the ability of the corneal endothelium to repair its damaged DNA is fundamental to its survival and that a failure to do so may underlie a variety of corneal problems in which endothelial failure is a common feature.

Adult↗
PubMed1980

Preliminary observations on human trabecular meshwork cells in vitro.

This report presents our preliminary observations on the trabecular meshwork from human eyes up to 5 days post-mortem in tissue culture. Satisfactory primary cultures were obtained from about 20% of the 423 explants which were investigated. The period prior to growth was from 4 days to 4 weeks and from the appearance of the initial outgrowth it took 25 to 30 days to reach maximum cellular spread within the culture chambers. The progress of the explant and the spreading of the trabecular meshwork cells was monitored by phase-contrast microscopy, time-lapse cinephotomicrography, light microscopy, transmission electron microscopy, scanning electron microscopy and autoradiography (using tritiated thymidine). On the basis of their ultrastructural appearance the cultured meshwork cells seems to be metabolically active. Their cytoplasm contained abundant rough endoplasmic reticulum, many mitochondria, a well developed Golgi apparatus and many coated and uncoated micropinosomes. However, even in short-term culture the trabecular meshwork cells had adapted to the artificial environment of our system and no longer resembled "normal" trabecular meshwork cells as seen in vivo. Since trabecular meshwork cells can quickly adapt their morphology in a culture environment and because the adult human meshwork contains a significant population of non-trabecular cells, the value of long term culture as a means of investigating the cellular activity of the normal and glaucomatous outflow system must be open to question.

Culture Techniques↗
PubMed1980

Prevalence rates for the neuroses: pitfalls in the evaluation of familiality.

A survey was made of studies reporting population prevalence rates for the different types of neurotic disorders in order to determine the utility of these rates for familial and genetic research. Rates varied considerably among studies both for all neuroses and for particular types of neuroses, even among studies using similar methods examining similar populations. The method of case ascertainment (personal interview versus record searches) and the threshold for defining an individual as affected are important contributors to variation. The use of the published prevalence rates for quantifying familial and genetic effects on the neurotic disorders would be premature.

Actuarial Analysis↗
PubMed1980

Biological component of the NIMH clinical research branch collaborative program on the psychobiology of depression: I. Background and theoretical considerations.

There are many reports which suggest that patients with effective illness (mania and/or depression) have abnormalities in the functioning of one or more neurobiological systems. At a conference convened by the Clinical Research Branch, Division of Extramural Research Programs, National Institute of Mental Health, these findings were reviewed and some of the factors impeding movement towards a more complete and integrated view of the functioning of neurobiological systems in patients with mania or depression were identified. As a result, a multi-research centre, collaborative approach to the study of the psychobiology of affective disorders was developed. In this collaborative programme, which has now been underway for several years, the focus has been upon: (a) the assessment of the functioning of several different types of biological systems in the same patient, both before and during treatment; (b) obtaining a reasonably large number of patients and comparison subjects; and (c) the use within and across centres of standardized diagnostic categories and behavioural rating methodologies. In this paper the history, background, and rationale for this collaborative effort are reviewed. Those biological systems chosen for study are noted, and issues such as reliability and validity of diagnoses, measurement of state variables, assessment of change with treatment, and logistical and coordinating problems are discussed.

Affective Disorders, Psychotic↗