Removal of central venous catheter and venous air embolism.
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Biomedical subjects
Publications and source records attributed to J L Peters.
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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.
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.
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.
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.
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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.
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.
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.
High resolution two-dimensional electrophoresis of cerebrospinal fluid (CSF) from 10 schizophrenic patients demonstrated a 21% average difference in the number of proteins which could be detected in patients undergoing haloperidol therapy when compared with CSF from the same patients after withdrawal from neuroleptic treatment. Proteins affected were trace proteins, as we found no significant variation in either the total CSF protein content or the integrated protein density on each electrophoretic gel. Three mechanisms which might account for these observations are: (1) a small change in liver protein synthesis or degradation would have little if any visible effect on the concentration of major blood or CSF proteins, such as albumin, but it could significantly alter trace proteins, such as alpha 2-haptoglobin, since their concentrations are orders of magnitude less than that of the major proteins, (2) haloperidol might alter the blood-CSF protein filtration system which could affect the visibility of the trace proteins, and (3) proteins synthesized in the Central Nervous System (CNS) or enhanced in the CSF could be differentially affected by haloperidol. While additional research will be required to determine the basis for the effects of haloperidol on CSF proteins, the current studies provide information which may be helpful in delineating disease specific protein alterations from those induced by drug therapy.
Administration of naloxone (100 mg i.v.; approximately 1.21 mg/kg body weight0.75) to 10 intact calves (24 weeks of age) caused an acute release of LH that was similar in amplitude and duration to spontaneous discharges of LH that occur at the same age. The naloxone-induced release of LH was abolished in 9/10 calves (intact and castrated) treated with oestradiol-17 beta. To determine the ontogeny of opioid control of secretion of LH, 12 calves were randomly assigned to receive saline or naloxone (1.21 mg/kg body weight0.75, i.v.) at 3, 5, 7, 9, 11, 13, 17 and 21 weeks of age. At each age, blood was collected at 10-min intervals for 4 h and saline or naloxone was administered (i.v.) after collection of the 120-min sample. Before administration of naloxone, plasma LH values increased with age (P less than 0.01) but did not differ between the control and naloxone groups (age x treatment, P greater than 0.05). Administration of naloxone caused concentrations of plasma LH to increase at 3, 11, 13, 17 and 21 weeks of age (treatment x time, P less than 0.001). Concentrations of LH (saline vs naloxone, ng/ml) reached a maximum within 20 min after treatment at Weeks 3 (0.3 vs 1.2), 11 (0.6 vs 2.6), 13 (0.6 vs 3.7), 17 (1.1 vs 2.6), and within 40 min after treatment at Week 21 (1.0 vs 3.5).(ABSTRACT TRUNCATED AT 250 WORDS)
Four out of 13 drug-free relapsed schizophrenic patients improved with double-blind clonidine treatment. All responders were paranoid schizophrenic patients. Pretreatment growth hormone (GH) response to the clonidine challenge test (CCT) correlated significantly with clonidine treatment improvement in psychosis, anxiety, and negative symptom ratings. Spontaneous GH peaks following placebo correlated significantly with the behavioral change with clonidine treatment. Our data suggest that patients with normal or high alpha 2-receptor activity and "normal" cerebrospinal fluid (CSF) norepinephrine (NE) are likely to respond to clonidine treatment. Patients with either high or low CSF NE levels did not respond to clonidine treatment. CSF NE and 3-methoxy-4-hydroxyphenylglycol (MHPG) decreased significantly with clonidine treatment. Changes in CSF NE and MHPG did not correlate significantly with improvement in psychosis, but they correlated with changes in other behaviors.
We isolated myoglobin from sheep heart by homogenizing cardiac muscle in 70%-saturated ammonium sulfate, followed by chromatography on a column containing carboxymethyl(CM)-Sephadex gel. Two major isoforms of myoglobin, designated Mb 7.9 and Mb 8.1, were separated by chromatofocusing and were distinguished by their different patterns seen on either isoelectrofocusing or on electrophoresis on polyacrylamide gel. The isoelectric points of the major bands of Mb 7.9 and Mb 8.1 were 7.4 and 7.16, respectively. Both isoforms were identical in size when examined by gel filtration chromatography but differed slightly when analyzed by polyacrylamide gradient gel in the presence of sodium dodecyl sulfate. The Mr of Mb 7.9 (15,900 Da) is slightly smaller than that of Mb 8.1 (18,400 Da). When reacted against rabbit anti-sheep myoglobin, two isoforms also appeared as two nonidentical precipitin lines on agarose gel.
Effects of age and castration on secretion of luteinizing hormone (LH) and metabolism of hypothalamic monoamines were determined in Holstein bulls. Calves were assigned to be intact or castrated and killed at 8, 12, or 24 wk of age. Animals were castrated and bled every 10 min for 6 h at 96 and 24 h prior to slaughter, respectively. The stalk median eminence (SME), medial basal (MBH), and anterior-preoptic (AHA-POA) hypothalamic regions were obtained at slaughter and assayed for norepinephrine (NE), dopamine (DA), dihydroxy-phenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindole-acetic acid (5-HIAA) using high performance liquid chromatography with electrochemical detection (HPLC-EC). Concentrations of LH and testosterone in plasma were determined by radioimmunoassay (RIA). In intact calves, LH pulse frequency (pulses/6 h) increased between 8 and 12 wk (1.4 vs. 3.4) and then declined (1.6 at 24 wk of age). Frequency of LH discharges did not change during the first 72 h post-castration in calves 8 (1.4 vs 1.0) and 12 (3.4 vs. 3.8) wk of age, but increased in 24-wk-old calves during this time (1.6 vs. 6.4). The amplitude of LH pulses increased with age (p less than 0.05) and after castration (p less than 0.05). There were marked regional differences in concentrations of monoamines. However, effects of age and castration on concentrations of monoamines were observed only within the SME where DA, DOPAC and NE increased significantly with age. Plasma concentrations of testosterone were correlated with concentrations of NE and DOPAC within the SME. Changes in 5-HT with age were biphasic; at each age, 5-HT increased after castration. From these data, it is concluded that 1) different mechanisms regulate LH pulse frequency and amplitude in calves as early as 8 wk of age, and 2) differences in hypothalamic metabolism of monoamines may be related to maturational changes in secretion of LH in bull calves.
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