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Biomedical subjects

J L Peters

Publications and source records attributed to J L Peters.

At least 55 records · Page 3Linked to original sources
PubMed1994

CSF levels of diazepam-binding inhibitor correlate with REM latency in schizophrenia, a pilot study.

CSF diazepam-binding inhibitor-like immunoreactivity (DBI-LI) and polysomnography were studied in 28 drug-free male schizophrenic (DSM-III-R) patients. They underwent a three-night polysomnography evaluation and a lumbar puncture. CSF DBI-LI correlated positively with REM latency, the REM latency/2d nonREM period ratio and stage-4% sleep, and negatively with stage-1% sleep. CSF DBI-LI did not correlate significantly with duration of sleep or sleep latency. CSF DBI-LI during haloperidol treatment did not correlate significantly with sleep EEG measures. The results of this first study of the relationship between endogenous DBI and sleep in humans suggest that physiological effects of DBI other than interactions with the BZD/GABAA receptor complex may explain its positive effects on sleep. However, the absence of similar sleep data in normal subjects precludes us from establishing a specific relationship between DBI and sleep in schizophrenia.

Adult↗
PubMed1994

Monitoring normal and aberrant electrocardiographic activity from an endotracheal tube: comparison of the surface, esophageal, and tracheal electrocardiograms.

INTRODUCTION: We designed an endotracheal (ET) tube with orthogonally spaced ECG cuff electrodes. This ET tube was evaluated in dogs and sheep to determine (1) whether ECGs recorded from our tube were sufficient to make accurate clinical decisions concerning heart rate and rhythm; and (2) whether metallic cuff electrodes in direct contact with the trachea could induce mucosal burn injury during episodes of defibrillation. METHODS: Using experimental animals, we obtained ECGs from their tracheae and compared our findings with ECGs obtained from surface and esophageal electrodes. The electrical activity of the heart was modified by increasing the depth of anesthesia, occluding the left coronary artery, and administering beta-adrenergic drugs. Before the dogs were euthanized, they were subjected to episodes of transthoracic and intrathoracic defibrillation at energy levels of 200 to 400 J. A postmortem pathological examination of the trachea was performed to determine the incidence of mucosal burn injury. RESULTS: Tracheal electrocardiography provided valid information on heart-rate monitoring and certain morphology profiles. The R-R, PR, QRS, and QT intervals measured from the trachea had a correlation of 1.0, 0.96, 0.83, and 0.98, respectively, when compared with the same intervals obtained from surface electrodes. Two tracheae subjected to intrathoracic defibrillation at > 300 J revealed evidence of minor burn injury. Some localized epithelium loss was displayed in all tracheae; we attributed this to tracheal intubation. CONCLUSION: Tracheal electrocardiography may be useful in trauma patients who require intubation where injury precludes placement of chest ECG electrodes.

Animals↗
PubMed1994

Platelet aggregation and dense granule secretion in schizophrenia.

The functional state of platelets and their possible impairment in response to various stimuli were assessed in saline-diluted citrated blood samples of normal male control subjects (n = 27), and in schizophrenic patients with (n = 34) and without (n = 23) haloperidol treatment. In response to collagen, but not to arachidonic acid (AA) and adenosine diphosphate, platelet aggregation (as measured by changes in impedance) was significantly higher in both haloperidol-treated and drug-free schizophrenic patients than in normal control subjects. Comparison of the secretion traces, however, indicated that only AA-induced adenosine triphosphate (ATP) release was significantly lower in haloperidol-treated schizophrenic patients than in normal control subjects. In response to thrombin, collagen, and AA, the mean values of ATP release from drug-free patients were significantly higher than those from the same individuals when they were receiving haloperidol. Furthermore, there was a trend toward increased ATP release (in response to thrombin or collagen) in the nonrelapsed group of drug-free schizophrenic patients as compared with the relapsed group. The collagen-induced platelet aggregation or dense granule secretion in drug-free patients was correlated significantly and negatively with psychosis ratings. Such changes in platelet function of schizophrenic patients were not correlated significantly with daily haloperidol dose, plasma haloperidol levels, age of subjects, age of onset, or duration of illness.

Adenosine Triphosphate↗
PubMed1994

Localization of nicotinic cholinergic receptors in rat brain: autoradiographic studies with [3H]cytisine.

There is a great deal of interest in the role of nicotinic acetylcholine receptors in the central nervous system, although their function is not well understood at present. Currently, central nicotinic receptors can be classified broadly as either alpha-bungarotoxin binding sites with low affinity for acetylcholine agonists, or as high-affinity agonist binding sites with low affinity for alpha-bungarotoxin. Neuronal nicotinic receptors with a high affinity for agonists are distributed widely in the central nervous system. Evidence from molecular biology and electrophysiology suggests that multiple nicotinic receptor types exist in the brain. In this study we have used the agonist [3H]cytisine as a ligand for autoradiography to generate a detailed quantitative map of the high-affinity agonist binding nicotinic receptor in the rat brain. Optimized binding conditions, characterization of the kinetic and equilibrium binding properties, and demonstration of the nicotinic pharmacology of this binding site in tissue sections confirm the usefulness of [3H]Cytisine as a ligand for nicotinic receptor autoradiography. [3H]Cytisine autoradiography provides excellent anatomic resolution with very low non-specific binding. This property has allowed us to describe variations in receptor density within subnuclei and gradients of receptor density in larger brain regions. Data from several studies suggest that the predominant high-affinity agonist binding nicotine receptor in the central nervous system is composed of the alpha 4 and beta 2 subunits. The data in the current study are consistent with the suggestion that [3H]cytisine labels only the alpha 4 beta 2 nicotinic receptor with high affinity, offering the possibility of localizing a specific nicotinic receptor subtype in the central nervous system. In summary, we characterize the optimum experimental conditions for the use of [3H]cytisine in tissue section autoradiography. [3H]Cytisine proves to be an excellent marker for nicotinic cholinergic receptors with a very high affinity and very low background. We provide a detailed quantitative characterization of nicotinic receptor density in the rat central nervous system and we find there are significant variations and gradients in receptor density within specific brain regions, including subregions previously thought to be homogeneous.

Alkaloids↗
PubMed1994

Noradrenergic activity and prediction of psychotic relapse following haloperidol withdrawal in schizophrenia.

OBJECTIVE: The purpose of this study was to develop a model based on the authors' previous studies to identify which neuroleptic-treated schizophrenic patients are at risk of early relapse following drug withdrawal. METHOD: Clinical and CSF monoamine-related variables obtained for 50 male haloperidol-treated, schizophrenic patients were used in a logistic regression model to identify those who relapsed (N = 24) within 6 weeks after placebo substitution and those who did not (N = 26). RESULTS: The oral dose of haloperidol, weight, CSF norepinephrine, 3-methoxy-4-hydroxyphenylglycol and chromogranin A-like immunoreactivity, and the anxiety and paranoia subscale ratings of the Brief Psychiatric Rating Scale produced a model that correctly predicted 18 relapsers and 21 nonrelapsers. By including the interactions of paranoia subscale by CSF norepinephrine and anxiety by CSF norepinephrine, the model correctly identified 20 relapsers and 23 nonrelapsers with a sensitivity and specificity of 83% and 88%, respectively. CONCLUSIONS: Increased noradrenergic activity during chronic dopamine blockade may be an episode marker and may predict relapse within 6 weeks following haloperidol withdrawal in schizophrenia. Effective relapse prediction models have important practical implications for the treatment of schizophrenia and the understanding of the psychotic relapse process.

Adult↗
PubMed1994

Age-related changes in the secretion of LH in vivo and in vitro in infantile and prepubertal Holstein bull calves.

The objectives of this study were (i) to determine whether age-related changes in the secretion of LH are associated with alterations in secretory activity or numbers of gonadotrophs, and (ii) to determine whether gonadotrophs obtained from the pars distalis and pars tuberalis undergo similar age-related changes in function. Blood samples were collected from Holstein bull calves every 15 min for 12 h at < 1, 12, and 42 weeks of age (n = 5 per age group) to characterize the secretion of LH. Calves were killed 3-5 days later. The pars distalis and pars tuberalis were enzymatically dispersed into suspensions of single cells. Cells from the pars distalis were (i) extracted with 0.01 mol NaHCO3 l-1, (ii) fixed for immunocytochemical analysis, and (iii) cultured in six-well plastic plates at a density of 500,000 cells per well in media containing 2.5% homologous calf serum for 18 and 72 h. Cells from the pars tuberalis were cultured as for pars distalis cells. As expected, LH pulse frequency increased (P < 0.01) between one and 12 weeks of age and then declined. The percentage of cells from the pars distalis containing immunoreactive LH averaged 8.4%, and did not change with age. The mass of the pars distalis and the total number of cells recovered increased with age (P < 0.05); consequently, the number of gonadotrophs recovered also increased. The initial content of LH of pars distalis cells changed with age and was greatest at 12 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

The superoxide dismutase mimic TEMPOL protects cultured rabbit lens epithelial cells from hydrogen peroxide insult.

The superoxide dismutase mimic, 4-hydroxy TEMPO (TEMPOL), was used to investigate the mechanism by which H2O2 damages cultured rabbit lens epithelial cells and to identify some of the targets of H2O2 insult. Most studies aimed at determining the mechanism by which H2O2 exerts its cytotoxic effect have used iron chelators to prevent the generation of the damaging hydroxyl radical. Since TEMPOL does not chelate transition metals, we were afforded an additional means of investigating the mechanism by which H2O2 exerts its cytotoxicity. Cells at low or high density were cultured in MEM containing 5 mM TEMPOL and exposed to a single sub-lethal dose of 0.05 or 0.5 mM H2O2, respectively. Analysis of EPR spectra indicated that TEMPOL was stable in MEM, did not destroy H2O2 and penetrated the intracellular fluid. TEMPOL prevented or curtailed the H2O2-induced inhibition of cell growth, blebbing of the cell membrane, the decrease in NAD+, the activation of poly ADP-ribose polymerase, an enzyme involved in DNA repair, and limited the induction of single strand breaks in DNA normally brought about by H2O2. TEMPOL did not prevent the H2O2-induced decrease in reduced glutathione, lactate production, and the activity of glyceraldehyde 3-phosphate dehydrogenase, or the H2O2-induced increases in oxidized glutathione and hexose monophosphate shunt activity. Addition of TEMPOL 1-15 min after exposure of cells to H2O2 offered partial protection from the inhibition of cell division. TEMPOL at 5 mM did not inhibit cell growth. These results, coupled with our other findings suggest that some of the H2O2-induced damage in cultured rabbit LECs is mediated by intracellular redox-active metals involved in the Haber-Weiss cycle. Cellular changes not protected by TEMPOL, including attack of H2O2 on the thiol groups of GSH (mediated through glutathione peroxidase) and G3PDH, are likely brought about by H2O2 itself and not by reactions of oxygen free-radicals generated from H2O2.

Animals↗
PubMed1993

Hemodynamic effects of gadodiamide injection and gadopentetate dimeglumine in anesthetized dogs.

A nonionic (gadodiamide injection) and an ionic (gadopentetate dimeglumine) contrast medium were compared for their effect on hemodynamics in the anesthetized, open-chest dog. Both agents were administered i.v. over 15 s at dosages of 1.0 and 1.5 mmol/kg, in randomized order. Both contrast agents resulted in transient but statistically significant decreases in aortic pressure, left ventricular pressure, indices of left ventricular contractility and relaxation, and systemic and pulmonary vascular resistance, and increases in aortic blood flow. At each dosage investigated, the changes associated with the administration of gadodiamide injection were of significantly smaller magnitude than those seen after gadopentetate dimeglumine and returned to preadministration levels sooner. The results from this study confirm that gadodiamide injection produces less severe alterations in hemodynamics than gadopentetate dimeglumine.

Anesthesia, Inhalation↗
PubMed1992

Sleep in schizophrenic patients on and off haloperidol therapy. Clinically stable vs relapsed patients.

We examined the state-dependent contribution of neuroleptic withdrawal and psychotic relapse in influencing sleep measures. Eighteen clinically stable male schizophrenic patients taking haloperidol were studied with 3 nights of polysomnography for baseline measures and again after neuroleptic withdrawal. Sleep measures were also obtained at the point of relapse (n = 9) or after a 6-week drug-free period if the patient remained clinically stable (n = 9). Neuroleptic withdrawal led to a global deterioration of rapid eye movement and non-rapid eye movement sleep and a reduction of rapid eye movement latency in both groups. Relapsers differed from nonrelapsers in that they had a larger decrease in total sleep time, sleep efficiency, total non-rapid eye movement sleep, and stage 2 sleep. The level of psychosis was inversely correlated with sleep efficiency, total sleep time, and stage 4 sleep in the drug-free patients. Our data suggest that clinical state needs to be identified in sleep studies of drug-free patients.

Adult↗
PubMed1992

CSF chromogranin A-like immunoreactivity in schizophrenia: relationships with REM latency and slow wave sleep.

Chromogranin A (CgA) is a calcium binding protein and a precursor of modulatory peptides in the brain. We measured CgA-like immunoreactivity (CgA-LI) in cerebrospinal fluid (CSF) in 15 male schizophrenic patients (diagnosed by DSM-III-R criteria) after 3 nights of polysomnography. Patients had been drug free for at least 33 days. Our earlier report that CSF CgA-LI in schizophrenic patients correlated significantly with negative symptoms and ventricle-brain ratios, which have been related to slow wave sleep, raised the possibility that CgA-LI might relate to slow wave sleep. CSF CgA-LI was significantly correlated with stage 4 sleep and rapid eye movement latency. Whether these positive relationships between CSF CgA-LI and electroencephalographic sleep measures are specific for schizophrenia awaits further study.

Adult↗
PubMed1992

Pupillary constriction during haloperidol treatment as a predictor of relapse following drug withdrawal in schizophrenic patients.

It has been proposed that the autonomic nervous system is dysregulated in schizophrenia. We hypothesized that measures of autonomic function, even during neuroleptic stabilization, might predict relapse following withdrawal of medication. Previously, shorter latencies to maximum pupillary constriction have been reported to differentiate acutely hospitalized schizophrenic patients from control subjects. Pupillary light reactions were recorded weekly from 19 chronic schizophrenic inpatients who were initially maintained on haloperidol and subsequently were withdrawn from medication under double-blind, placebo-controlled conditions. Patients were then classified as either relapsed or nonrelapsed (clinically stable) during the drug-free period. During the treatment phase, a shorter latency to maximum pupillary constriction significantly distinguished patients who were later to relapse from the nonrelapsers. The potential use of autonomic activity as an indicator of prodromal sensitivity was supported. In addition, these findings emphasize the need for classification of drug-free patients according to clinical status.

Adult↗
PubMed1992

Delta sleep-inducing-peptide-like immunoreactivity (DSIP-LI) and delta sleep in schizophrenic volunteers.

Delta sleep-inducing-peptide (DSIP) has been reported to increase sleep in subjects with insomnia. The authors studied cerebrospinal fluid (CSF) DSIP-like immunoreactivity (DSIP-LI) in 15 drug-free male subjects with a DSM-IIIR diagnosis of schizophrenia. The subjects underwent a lumbar puncture and three nights of polysomnography. CSF DSIP-LI was significantly correlated with polysomnography the night before the LP: with stage 3 sleep (p = 0.05), stage 3 and delta (stages 3 + 4) sleep during the first nonrapid eye movement NREM period (p = 0.02 and p = 0.05, respectively) and the ratio of the first and second NREM period (p < 0.05), and negatively with stage 2% sleep (p < 0.05). Whether this first report of a potential relationship between CSF DSIP-LI and slow-wave sleep in man might be generalized to sleep in nonpsychiatric subjects awaits further study.

Adult↗
PubMed1992

Prolactin variants in ram adenohypophyses vary with season.

Secretion of PRL in sheep is affected by photoperiod being highest during the spring and summer, lowest in fall and winter. The objectives of this study were to determine if 1) the production of variant forms of PRL, and 2) immuno- and bioactivities of PRL (iPRL and bPRL) differ during times of the year selected to represent periods of low, transitional and high PRL secretion. Twelve mature rams were maintained on pasture and killed in October, December, and April (n = 4/month). Individual pituitary glands were dispersed, cells obtained, and fixed for immunocytochemical flow cytometry, extracted with 0.01 N NaHCO3 or cultured in serum-free, defined media. The Mr of PRL extracted from cells immediately following dispersion ranged from 14-140K, with significantly more bands greater than 40K being detected from rams sacrificed in December than from those killed in October and April (P less than 0.01). No bands of PRL greater than 25K were observed when samples were reduced with beta-mercaptoethanol prior to electrophoresis, indicating that the high Mr forms were disulfide-linked aggregates. Culture media from October and April contained variants of PRL that ranged from 22-40K but those greater than 25K were generally not observed from cells harvested during December. Extracts of cells after 24 h in culture contained fewer high Mr species during December than had been present in initial extracts from that month. In contrast, during April more high Mr intracellular forms were present after culture than had been detected prior to culture during that month. The percentage of lactotrophs averaged 50.0 +/- 2.5, 47.4 +/- 5.7, and 59.4 +/- 5.5 for October, December, and April, respectively. Initial lactotroph content (pg/lactotroph) of iPRL was higher (P = 0.06) in April (46.0 +/- 17.0) when compared to October and December (8.0 +/- 2.0 and 20.0 +/- 10.0, respectively). In contrast, the bPRL content of initial extracts was higher (P = 0.05) in December (267.0 +/- 68.0) than in October (101.0 +/- 35.0), but not than in April (190.0 +/- 70.0). Although iPRL and bPRL concentrations in culture media were similar for the 3 months, the intracellular iPRL (P less than 0.001) and bPRL (P less than 0.0001) content after culture was greatest during April. In summary, in addition to the well-documented seasonal changes in blood concentrations of PRL, different molecular forms of PRL were found within the pituitary at different times of the year and seasonal variations in iPRL and bPRL did not occur in parallel.

Animals↗
PubMed1992

The expert witness in forensic psychiatry.

Forensic psychiatry operates at the interface of the Justice and Health systems and has been defined as: "That branch of psychiatry which requires special knowledge and training in the law as it relates to the mental state of the offender, or alleged offender" [1]. As a consequence of working in this area, psychiatrists are often called into court to give evidence as "expert witnesses". This article examines some of the professional and legal issues involved in providing expert testimony. Secondly, it aims to outline some practical guidelines for giving evidence in the court-room. The predominant focus is on criminal, rather than civil, proceedings in which the forensic psychiatrist gives expert testimony; however much of the information is also relevant to other psychiatrists and psychologists undertaking this role in the legal arena.

Commitment of Persons with Psychiatric Disorders↗
PubMed1992

Cerebrospinal fluid protein variations in common to Alzheimer's disease and schizophrenia.

Analysis of silver stained two-dimensional (2D) gels of cerebrospinal fluid (CSF) from 27 patients with schizophrenia (SCZ) and 10 patients with Alzheimer's disease (AD) revealed an increase in the relative amount of a polypeptide of 18,000M(r) and isoelectric point of 6.5 when compared to the appropriate controls. This protein was identified by its electrophoretic characteristics and by immune analysis of Western blots as an isoform of alpha-2 haptoglobin, provisionally identified as alpha-2FS haptoglobin. Alzheimer's disease versus control CSF samples showed a 6.8-fold increase in the percent mean density value of this haptoglobin isoform (n = 10 AD vs 11 control; P > 0.025) while a 4.4-fold increase was observed in the schizophrenic patients (n = 17 SCZ vs 10 control; P > 0.001). Two additional polypeptides (proteins '127' and '128') of 40,000 M(r) and isoelectric points 5.7 and 5.9, respectively, described previously by this laboratory, were found in the CSF of 27% of schizophrenics, 23% of the Alzheimer's disease patients, and 4% of the controls in the current study. The presence of proteins 127 and 128, as well as the increased concentrations of alpha-2 haptoglobin in the CSF of Alzheimer's disease and schizophrenic patients, may be useful as diagnostic biological markers. They may also indicate a common pathophysiology between these diseases.

Acute-Phase Proteins↗