Decreased beta-phenylethylamine in CSF in Parkinson's disease

OBJECTIVE: To determine the concentrations of beta-phenylethylamine (PEA) in CSF in patients with Parkinson's disease, and to evaluate the relation between concentration of PEA in CSF and severity of Parkinson's disease. METHODS: Using gas chromatography-chemical ionisation mass spectrometry, CSF concentrations of PEA were measured in 23 patients with Parkinson's disease (mean age, 64.0 (SD 8.2) years), of whom three were at Hoehn and Yahr stage II, 11 were at stage III, and nine were at stage IV. Comparison was made with eight patients with neuropathy (mean age, 57.0 (SD 19.2) years) and 12 controls without neurological disease (mean age, 57.6 (SD 4.8) years). RESULTS: Concentrations of PEA in CSF in Parkinson's disease were significantly lower (mean 205 (SD 131) pg/ml) than in patients with peripheral neuropathy (433 (SD 254) pg/ml) and controls (387 (SD 194) pg/ml). The concentrations of PEA in CSF correlated negatively with Hoehn and Yahr stage (P<0.01). CONCLUSIONS: There are decreased CSF concentrations of PEA in patients with Parkinson's disease.     

Depression in Parkinson's disease: clinical correlates and outcome

Depression has been shown to be more common in Parkinson's disease (PD) than in other chronic and disabling disorders. Neurochemical and functional disturbances are important etiopathogenic factors. The prevalence and clinical features associated with depression in PD remain controversial. The purpose of this study is to estimate the prevalence of depressive symptoms in our patients, as related to other clinical data, and to assess clinical outcomes of these symptoms. A series of PD patients were evaluated over a 9-year period, using the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr stage (HY), Schwab and England Scale (SE), Mini-Mental State Examination (MMSE), and Yesavage Geriatric Depression Scale (GDS). Presence of depressive symptoms was considered if GDS score was higher than 10: mild-moderate (MD) for GDS scores between 11 and 20 and moderate-severe (SD) for GDS scores greater than 20. Three hundred and fifty-three patients were included in this study and additional follow up information was obtained for 184 patients. MD and SD were found in 40.2 and 16.7% of PD patients, respectively. Female gender, high HY, high UPDRS total and subtotal, and low MMSE and SE scores were significantly associated with depressive symptoms. According to changes in GDS score, 34% of patients remained stable, 35% showed an improvement, and 30.9% worsened in the follow up study. Gender, age, age of onset, HY, UPDRS, and PD duration are not related to depression outcome.     

The effects of target and distractor familiarity on visual search in de novo Parkinson's disease patients: Latent inhibition and novel pop-out.

De novo Parkinson's disease (PD) patients identified presence or absence of a unique shape presented with homogeneous distractors. Response time (RT) was examined as a function of prior experience with target and/or distractor assessing latent inhibition (LI; slower RTs to a target that was formerly a distractor against a background of distractors that were formerly targets as compared with a novel target with distractors that were formerly targets) and novel pop-out effects. PD patients were slower than controls in detecting test-phase targets compared with preexposure-phase targets. Female PD patients with right-side motor symptoms had elevated LI compared with female controls and female PD patients with left-side symptoms. Male PD patients with right-side symptoms did not exhibit LI. Results are discussed in terms of the dopamine hypothesis and the reciprocal relationship between PD and schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Determination of biogenic amines in cheese

A liquid chromatographic (LC) procedure for determining 10 biogenic amines in cheese is described. The method is based on ion-pair chromatography on a reversed-phase column with postcolumn derivatization with o-phthaldialdehyde and fluorometric detection. It allowed simultaneous determination of 10 amines in < 80 min: histamine, tyramine, tryptamine, 2-phenylethylamine, serotonin, agmatine, spermine, spermidine, putrescine, and cadaverine. Linearity for each amine was observed between 0.5 and 6.0 micrograms/mL. Detection limits ranged form 0.004 to 0.009 micrograms/20 microL, and determination limits ranged from 0.066 to 0.149 mg/100 g. Amino acids and other amines did not interfere with determination of biogenic amines. Three extractants--methanol, hydrochloric acid, and trichloroacetic acid--were compared in their efficiency to recover amines from spiked samples. Purification of the cheese extract was required prior to LC to avoid interference from compounds in the cheese matrix. Hydrochloric acid extraction followed by purification with diethyl ether gave best recoveries for all the amines (75.5-112.3%). The method is simple, fast, and reliable. It can be used to study the technological and toxicological implications of biogenic amines in cheeses.     

Mast cells and biogenic amines in radiation-induced pulmonary fibrosis

OBJECTIVE: To determine womens' beliefs regarding the risks and health benefits of oral contraceptives (OCs). METHODS: Between April 26 and June 7, 1991, 247 women completed a self-administered questionnaire at the Yale University Health Services evaluating their perceptions of the risks and benefits of OC agents. RESULTS: The mean age of the study population was 30.2 years (range 16-68), and more than 90% of the study group had at least 1 year of college education. Forty-nine percent of the study group believed there are substantial risks to OC use. Between 80-95% of women were unaware of the following health benefits of OCs: decreased risks of endometrial cancer, ovarian cancer, pelvic inflammatory disease, ectopic pregnancy, anemia, and benign breast disease. CONCLUSIONS: Perceptions of the risks of OCs are exaggerated and there is a clear knowledge deficit with regard to their health benefits. Increased educational efforts by health care providers should emphasize the health benefits of OCs and attempt to dispel the common misconceptions.     

Blood biogenic amines during clozapine treatment of early-onset schizophrenia

The aims of this investigation were to evaluate long-term and short-term effects of clozapine-treatment on plasma biogenic amines and psychopathology measures in adolescents with schizophrenia (DSM-III-R criteria). The long-term study was conducted in a study sample of 40 young patients (age 14-22 years) following a mean of 3.4 years of neuroleptic treatment. During the study, 20 patients received clozapine, and the other 20 patients were treated with standard neuroleptic medications. At the beginning of the open clinical trials, the patients had already been receiving clozapine treatment for 24 +/- 15 months. Assessment of the biochemical and psychopathological measures was performed on six occasions at consecutive 6-week intervals during maintenance treatment with clozapine or conventional neuroleptics. Blood levels of serotonin, 3-methoxy-4-hydroxy-phenylglycol (MHPG), norepinephrine, and epinephrine were significantly higher in clozapine-treated patients than in conventionally treated patients. During long-term treatment, higher serotonin levels were associated with significantly fewer negative symptoms of schizophrenia, whereas higher MHPG levels were correlated with less depression. The short-term effects of clozapine were assessed in a second and independent study sample. After failing on conventional neuroleptics in clinical trials lasting a mean of 1.6 years, 15 inpatients (aged 11-20 years) received clozapine. Weekly ratings of psychopathological symptoms using standard rating scales were performed in parallel to blood samplings for measurements of biogenic amines and serum levels of clozapine. These measures were obtained for 6 weeks during conventional neuroleptic treatment and for 6 weeks during the open-label clozapine trial. Serum levels of serotonin and plasma norepinephrine levels were significantly higher during treatment with clozapine than during pretreatment with typical neuroleptics. A comparison of plasma epinephrine levels in responders (n = 7) and nonresponders (n = 8) to clozapine revealed that response to clozapine can be predicted by epinephrine levels prior to initiation of treatment with clozapine (responders ranging from 32.2 to 90.3 pg/ml; nonresponders ranging from 92.5 to 473.5 pg/ml). Additionally, subjects who responded to clozapine showed increased mean plasma concentrations of MHPG and epinephrine during treatment with this drug in comparison to the levels measured during pretreatment with typical neuroleptic medication. Nonresponders to clozapine failed to show this increase. Finally, in responders to clozapine a negative linear relationship between negative symptoms of schizophrenia and the concentrations of plasma norepinephrine and serum serotonin were observed. In conclusion, our results demonstrate that plasma epinephrine levels prior to initiation of clozapine therapy predict response to this atypical neuroleptic. Our findings derived from short-term and maintenance treatment with clozapine suggest involvement of norepinephrine, epinephrine and serotonin in the therapeutic actions of the atypical neuroleptic clozapine.     

Role of biogenic amines in the reversal of cycloheximide-induced amnesia.

Conducted 6 experiments with male C57BL/6J mice in which amnesia was induced by pretraining subcutaneous injections of cycloheximide (CYC) in a food motivated discrimination reversal task. Magnitude of amnesia varied as a function of the amount of training on both the initial discrimination and the reversal and also as a function of the length of intertrial interval used on both the reversal and the test. Memory spontaneously recovered 48 hrs following reversal training. Recovery from amnesia was induced by pretesting injections of dextroamphetamine and 2 monoamine oxidase inhibitors, pargyline and catron. This enhanced performance was a true recovery of the memory and not a result of enhanced learning or increased arousal. Depletion of catecholamines by alpha-methyl-para-tyrosine, a tyrosine hydroxylase inhibitor, and by diethyldithiocarbamate, a dopamine beta hydroxylase inhibitor, resulted in an amnesia quantitatively and qualitatively similar to amnesia induced by CYC. Data support the hypothesis that CYC-induced amnesia is mediated via central catecholamines. (44 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prevalence of heart disease diagnosed de novo in pregnancy in a West London population

OBJECTIVES: To determine the prevalence of heart disease diagnosed de novo in pregnancy in a West London population and to re-examine the current role of routine cardiovascular examination in antenatal care in the UK. DESIGN: Retrospective study. SETTING: Obstetric medical clinics at Queen Charlotte's and Chelsea Hospital, University College Hospital and Northwick Park Hospital. POPULATION: Three hundred and twenty women referred for cardiac evaluation during pregnancy. RESULTS: The majority of the 139 women referred specifically for evaluation of murmurs during pregnancy were found to have physiological murmurs (97%). Only four women (3%) were found to have significant cardiac lesions de novo in their pregnancy. Three of these four women were immigrants who had no previous history of heart disease. The only woman from the UK was already known to have a murmur from childhood. CONCLUSIONS: Our study shows that heart disease diagnosed de novo in pregnancy in a West London population is an uncommon problem with low prevalence. It also appears to be a problem seen mainly in the immigrant population. The results emphasise the importance of taking a thorough medical history in all pregnant women. However, our results if they are confirmed, would suggest that only immigrants and those with significant symptoms or a known history of heart murmur or heart disease need undergo cardiovascular examination during pregnancy. These findings need to be confirmed in a larger group in other parts of the UK before further recommendations on selective cardiovascular examination can be made. This will have significant implications for midwifery-led care.     

Localization of biogenic amines and neuropeptides in adrenal medullary cells of birds

The present article reviews the immunohistochemical findings on the localization of biogenic amines and neuropeptides in adrenal medullary cells of birds. In the chicken, about 70% of medullary cells are adrenaline-containing cells and the rest of cells seem to be noradrenaline-containing cells. The ratio of adrenaline-cells to noradrenaline-cells extremely varies among avian species. Besides adrenaline and noradrenaline, medullary cells of birds contain many kinds of biogenic amines and neuropeptides: serotonin, galanin, cholecystokinin, somatostatin, enkephalin, neuropeptide tyrosine and atrial natriuretic peptide. The existence of these bioactive substances in medullary cells also exhibits interspecies heterogeneity. In the chicken, serotonin and galanin are contained in both adrenaline- and noradrenaline-cells of the adrenal gland. Cholecystokinin- and somatostatin-immunoreactivity is restricted to adrenaline-containing cells. Enkephalin-immunoreactivity is seen in both adrenaline- and noradrenaline-cells, but in about half of medullary cells. Neuropeptide tyrosine-immunoreactivity is found in the adrenal gland of the chick embryo and newly hatched chick, but not in the adult chicken. Serotonin and these neuropeptides may be selectively coreleased with adrenaline and/or noradrenaline from adrenal medullary cells of the chicken.     

Acquired colour deficiency in patients with Parkinson's disease

The blue cone pathway is reported to be affected early in Parkinson's disease (PD) and acquired type three (tritan) defects may occur. Sixty-one patients attending a treatment and rehabilitation centre for PD were examined with clinical colour vision tests. Seven of 13 patients, for whom the diagnosis of PD was equivocal or who had other medical conditions, were identified as having tritan colour deficiency. Results for the remaining 44 PD patients were compared with 40 age matched controls. Ten PD patients (22.7%) had tritan defects. Tritan defects were not found in the control group but performance on some tests was age related. We conclude that clinical tests for tritan colour deficiency are unlikely to be helpful in identifying PD.     

Benzodiazepine prevention of swim stress-induced sensitization of cortical biogenic amines: an in vivo microdialysis study

In vivo microdialysis was used to determine the effect of diazepam, flumazenil and FG-7142 upon the biogenic amine response to acute and repeated swim stress in the medial prefrontal cortex of the rat. Acute swim stress increased norepinephrine levels, although dopamine and serotonin levels remained stable. Upon re-exposure to swim stress twenty-four hours later, sustained increases (200-300% of baseline) in all three biogenic amines were detected. This enhanced response to re-stress was not seen in rats pretreated with either a benzodiazepine: agonist (diazepam, 2 mg/kg), an antagonist (flumazenil, 10 mg/kg), or an inverse agonist (FG-7142, 10 mg/kg) given prior to the first swim stress. Therefore, the sensitization of biogenic amine response to re-stress may be prevented by compounds which differ in their activity at the benzodiazepine receptor.     

Respiratory-chain enzyme activities in isolated mitochondria of lymphocytes from untreated Parkinson's disease patients. Grupo-Centro de Trastornos del Movimiento

We studied respiratory-chain enzyme activities in lymphocyte mitochondria from 36 untreated Parkinson's disease (PD) patients and in 30 age- and sex-matched healthy controls. The respiratory-chain enzyme activities did not differ significantly between patients and controls. Moreover, no patient showed respiratory-chain enzyme levels below normal range. Values for activities of complexes in the PD group did not correlate with age at onset, duration, scores of the Unified Parkinson's Disease Rating scales, or Hoehn and Yahr staging. These results suggest that the presence of defects of respiratory-chain complexes could depend on methodologic aspects, and that determinations of respiratory-chain enzymes in cell homogenates are not generally appropriate for evaluating abnormal mitochondrial dysfunction, especially when the amount of the specific enzyme is relatively low, as is the case of blood cells. In addition, the method of measuring complex I activity is critical for evaluating the results. In conclusion, our finding of normal mitochondrial function in lymphocyte mitochondria suggests that this tissue cannot be used to develop a diagnostic test for PD.     

Memory and learning strategies in patients with Parkinson's disease

Parkinson's disease patients (PD) do not differ from control subjects (CS) when they have to execute a problem solving task in which external cues for solving the problem are given. However, when PD have to solve a problem by means of an internally generated strategy, they show a serious decrease in performance. We hypothesised that this distinction may also apply to the way PD and CS organize recall. In order to test our hypothesis the California Verbal Learning Test (CVLT) was administered to 59 PD and 30 CS. The test consists of five learning trials using a 16-word target list, composed of four items from each of four semantic categories. The fact that the word list was built on this implicit organization was not divulged in advance. The sequence in which the words were read is fixed; each subsequent word belongs to a category being different from the category to which the preceding word belongs. The organization in recall according to the semantic categories is considered to be the result of an unprompted, internally generated strategy. Recall according to the sequence in which the words are read by the experimenter, is viewed as an externally offered strategy. The results prove to be in line with our hypothesis: unlike CS who appeared to rely mainly and increasingly on an internally generated semantic organization, PD showed evidence of gradually adhering more to the externally imposed serial sequence.     

Neural activity of the subthalamic nucleus in Parkinson's disease patients

The neural activity pattern of the subthalmic nucleus (STN) was investigated in five patients with Parkinson's disease who were scheduled for electrode implantation for chronic stimulation of the STN. The initial target was placed 8 mm or 10 mm lateral to the midline, 3 mm to 4 mm posterior to the midcommissural point, and 5 mm to 6 mm below the intercommissural (AC-PC) line. The STN was identified by semi-microelectrode recordings with a trajectory moving laterally in 2-mm steps. The amplitudes of multi-unit activities were relatively low at depths from 8 mm to 5 mm above and from 1 mm to 4 mm below the target, while those 4 mm to 0 mm above the target were significantly higher than at the other sites (ANOVA, Fisher's test, p < 0.05), with the highest amplitude at 2 mm above the target (91.0 +/- 23.3 mu v, n = 15). In the mediolateral direction, amplitudes were relatively higher in the lateral portion, and amplitudes at 14 mm lateral to the midline were significantly higher than at the other sites (ANOVA, Fisher's test, p < 0.05). The target for chronic electrical stimulation was determined to be at the midpoint of the hyperactive STN, i.e., 12 mm lateral to the midline in three patients and 13 mm lateral in two patients. Movement-related neural activity was observed at 5 sites, i.e., 3 sites responded to passive movement of the contralateral wrist and 2 sites to passive knee and/or ankle movement. In conclusion, our data show that the lateral part of the STN is hyperactive in PD, and recordings of neural activities contributed greatly to identifying the STN and determining the target for chronic stimulation within it.     

Bilateral posteroventral pallidotomy in advanced Parkinson's disease in three patients

In this report, we describe the effect of staged bilateral posteroventral pallidotomy in three patients with advanced Parkinson's disease who were all of the young-onset type. Two patients had developed response fluctuations after the use of levodopa, with severe hypokinesia, painful dystonia, and rigidity in the "off" phase and violent dyskinesias in the "on" phase. One patient, in a continuous hypokinetic rigid state, was totally unresponsive to dopaminergic medication. All were at Hoehn and Yahr stage 5 in the "off" phase before surgery. After surgery, the hypokinetic state was reversed and dyskinesias were abolished in all patients. Hoehn and Yahr stages were 3 in the "off" phase postoperatively. Overall functional improvement was marked and lasting after follow-up for 7, 12, and 13 months, respectively. Complications were visual field deficit and transient central facial paresis, both in the same patient. Bilateral posteroventral pallidotomy can ameliorate response fluctuations, hypokinesia, rigidity, and painful dystonia in advanced Parkinson's disease.     

Clinical significance of micromegakaryocytes in de novo AML

Bone marrow specimens obtained from 54 patients with de novo AML and 7 patients with AML evolving from MDS were retrospectively examined for the presence of micromegakaryocytes defined as cells of less than 30 microns in diameter with one or two nuclei. At least 25 megakaryocytes were counted in each patient. Micromegakaryocytes were found in 17 cases (31%), M1:1/11, M2:5/18, M3:0/4, M4:5/12, M5:1/4, M6:4/4, M7:1/1. The median age of the patients was higher in de novo AML with micromegakaryocytes (57 years) than in de novo AML without micromegakaryocytes (41 years) (p = 0.014). Chromosomal analysis revealed that deletion of 5 or 5q-, 7 or 7q- was recognized only in the group of de novo AML with micromegakaryocytes and that t(15;17), t(8:21) and inv (16) were not recognized in this group. Micromegakaryocytes were identified in each bone marrow specimen obtained from 9 of 10 patients with de novo AML with trilineage myelodysplasia. The complete remission rate was significantly lower in de novo AML with micromegakaryocytes (33%) than in de novo AML without micromegakaryocytes (86%) (p = 0.001). The duration of survival of the patients with de novo AML with micromegakaryocytes was shown to be shorter than that of the patients with de novo AML without micromegakaryocytes (p = 0.017). Micromegakaryocytes were recognized in all of 7 patients with AML evolving from MDS. The presence of micromegakaryocytes in bone marrow of the patients with AML indicates a subset of AML with poor prognosis that may be closely associated with myelodysplastic syndrome.     

The determination of biogenic amines in four strains of the fruit fly Drosophila melanogaster

A range of biogenic amines were measured in the heads from four strains of Drosophila melanogaster. Quantitation was carried out using gas chromatography-negative ion chemical ionization mass spectrometry (GC-NICIMS) with stable isotope dilution. The principal amines detected in the heads were dopamine, noradrenaline and 5 HT with small amounts of p- and m-tyramine; p-octopamine could not be detected in samples of 25 heads with a limit of detection of 10 pg per sample. In addition to conventional neurotransmitters or putative neurotransmitters the amines 5- and 6-hydroxydopamine were detected in the heads in substantial amounts.