Evaluation of Parkinson disease and Alzheimer disease with the use of neuromelanin MR imaging and (123)I-metaiodobenzylguanidine scintigraphy.

BACKGROUND AND PURPOSE: Progressive changes in the substantia nigra pars compacta and locus ceruleus of patients with Parkinson disease and Alzheimer disease visualized by neuromelanin MRI and cardiac postganglionic sympathetic nerve function on (123)I-metaiodobenzylguanidine scintigraphy have not been fully evaluated. We compared the diagnostic value of these modalities among patients with early Parkinson disease, late Parkinson disease, and Alzheimer disease. MATERIALS AND METHODS: We compared contrast ratios of signal intensity in medial and lateral regions of the substantia nigra pars compacta and locus ceruleus with those of the tegmentum of the midbrain and the pons, respectively, by use of neuromelanin MRI in patients with early Parkinson disease (n = 13), late Parkinson disease (n = 31), Alzheimer disease (n = 6), and age-matched healthy control subjects (n = 20). We calculated heart-to-mediastinum ratios on (123)I-metaiodobenzylguanidine scintigrams after setting regions of interest on the left cardiac ventricle and upper mediastinum. RESULTS: The signal intensity of the lateral substantia nigra pars compacta on neuromelanin MRI was significantly reduced in early and late Parkinson disease, and that of the medial substantia nigra pars compacta was gradually and stage-dependently reduced in Parkinson disease. The signal intensity of the locus ceruleus was obviously reduced in late Parkinson disease. Signal reduction was not significant in the substantia nigra pars compacta and locus ceruleus of patients with Alzheimer disease. The heart-to-mediastinum ratio on (123)I-metaiodobenzylguanidine scintigrams was stage-dependently reduced in Parkinson disease and normal in Alzheimer disease. The signal intensity ratios in substantia nigra pars compacta and locus ceruleus on neuromelanin MRI positively correlated with the heart-to-mediastinum ratio on (123)I-metaiodobenzylguanidine scintigrams. CONCLUSIONS: Both neuromelanin MRI and (123)I-metaiodobenzylguanidine scintigraphy can help to evaluate disease progression in Parkinson disease and are useful for differentiating Parkinson disease from Alzheimer disease.

Probing the metal-insulator phase transition in the (DMEDO-EBDT)2PF6 single crystal by optical measurements.

The temperature and polarization dependence of the optical reflectivity  spectra of a quasi-one-dimensional 1/4-filled band system, (DMEDO-EBDT)(2)PF(6), have been investigated. We observed clear anisotropy in the electronic structures corresponding to the anisotropic transport properties. The appearance of a charge gap (E(g) > 0.1 eV) and transfer of the spectral weight accompanied by the metal-insulator phase transition were clearly observed. In addition, a split of the intramolecular vibrational modes was observed, which strongly suggested the existence of charge disproportionation in the low temperature phase. We also observed a photoinduced reflectivity change, which implied the occurrence of a photoinduced phase transition from the low temperature insulating phase to the high temperature metallic phase.

Assessment of dementia in patients with multiple system atrophy.

BACKGROUND AND PURPOSE: We investigated dementia in patients with multiple system atrophy (MSA) in order to characterize the prevalence and nature of impairments in these patients. METHODS: Fifty-eight MSA patients were recruited in our institution between April 1996 and December 2006 and investigated. RESULTS: Of 58 patients, 10 were diagnosed with dementia. There were no significant differences in age at onset, gender, duration of disease, or severity of cerebellar dysfunction between patients with and without dementia. The early and delayed heart to mediastinum (H/M) ratios obtained with (123)I-metaidobenylguanidine (MIBG) cardiac scintigraphy were significantly decreased in patients with dementia compared with those without dementia. Of the 10 patients with dementia, three were found to have cognitive decline that preceded onset of motor symptoms. White matter lesions were evident in these patients, whilst frontal atrophy was prominent in patients whose cognitive decline was preceded by onset of motor symptoms. CONCLUSIONS: Dementia in patients with MSA may be more common than previously thought, furthermore, we speculate that clinical features of dementia in these patients might be heterogeneous.

Assessment of hallucinations in Parkinson's disease using a novel scale.

OBJECTIVE: To assess hallucinations in Parkinson's disease (PD), we developed a novel practical rating scale that evaluates five items including variety, frequency, and severity of hallucinations, caregiver burden levels, and psychiatric status at nighttime. METHODS: Forty-one PD patients and their caregivers were examined regarding the status of the hallucinations associated with PD. RESULTS: As a measure of internal consistency, the Tottori University Hallucination Rating Scale (TUHARS) has a Cronbach's alpha of 0.88. Mini-Mental State Examination (MMSE) and Hoehn-Yahr stage were associated with the TUHARS scores in a multivariate regression analysis. Visual hallucinations are the most common. However, half of the patients who reported visual hallucinations also had other hallucinations. The scale scores in the PD patients with dementia (PDD) group were significantly greater than in the PD patients without dementia (PDnD) group. CONCLUSIONS: TUHARS appears to be a suitable and easily administered instrument for assessment of hallucinations in PD. PD patients experienced various kinds of hallucinations. Hallucinations may have a close relationship with cognitive decline in PD patients.

Executive dysfunction in non-demented Parkinson's disease patients with hallucinations.

OBJECTIVE: We investigated executive function in Parkinson's disease (PD) patients, and focused on executive dysfunction in PD with hallucinations, but without dementia. METHODS: PD patients were classified by cognitive or neuropsychotic status as PD group, PD with vivid dreaming group, PD with hallucinations group and Parkinson's disease dementia (PDD) group. Psychomotor speed tests, the Stroop test, a verbal fluency test and the Self-rating Depression Scale were performed. RESULTS: The PDD group showed poorer scores in every test compared with the PD group. The PD with hallucinations group showed results similar to those of the PDD group, while the PD with vivid dreaming group was similar to the PD group. CONCLUSIONS: The study suggests that PD patients with hallucinations, not extensive enough to qualify as dementia, already have executive dysfunction similar to that seen in PDD patients. Executive dysfunction may be an important substrate for hallucinations even when dementia is not yet apparent.

Clinical evaluation of Parkinson's disease dementia: association with aging and visual hallucination.

OBJECTIVES: In order to explore factors associated with the development of dementia in Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), we systematically investigated the clinical evaluation of PD and DLB patients hospitalized in the Department of Neurology at Tottori University Hospital, Japan. RESULTS: There were 208 patients diagnosed as having PD and 39 patients diagnosed with DLB in this study. Of the patients with PD, 67 (32%) developed dementia and only five PD+ patients were considered to have cognitive impairment attributable to Alzheimer's disease (AD) or vascular dementia (VaD). Fifty-four (81%) PDD patients had visual hallucinations (VH) with or without cognitive fluctuation. The onset age of parkinsonian motor symptoms of patients with PD dementia (PDD) did not differ from that of PD patients without dementia. There was a significant inverse correlation between the onset age of motor symptoms in PD and the onset of their dementia in PDD. Seventy-five (36%) patients with PD had experienced VH and most of the PDD patients had experienced VH within 1 year before or after diagnosis of PDD. CONCLUSIONS: These results indicate that aging and VH are important factors associated with dementia in PD.

In vitro pharmacological characterisation of a novel cyclic nociceptin/orphanin FQ analogue c[Cys(7,10)]N/OFQ(1-13)NH (2).

Nociceptin/orphanin FQ (N/OFQ) is the endogenous 17 amino acid peptide ligand for the G(i)-protein-coupled N/OFQ receptor (NOP). In an attempt to improve the metabolic stability of N/OFQ, we have produced a truncated cyclic analogue with cysteine residues at positions 7 and 10, c[Cys(7,10)]N/OFQ(1-13)NH(2) (c[Cys(7,10)]). c[Cys(7,10)], the template N/OFQ(1-13)NH(2) and N/OFQ displaced the binding of [(3)H]N/OFQ to Chinese hamster ovary cells expressing recombinant human NOP (CHO(hNOP)) with pK ( i ) values of 9.98, 9.83 and 9.18, respectively. In addition, c[Cys(7,10)], N/OFQ(1-13)NH(2) and N/OFQ stimulated the binding of guanosine triphosphate gamma [(35)S] to CHO(hNOP) cells with pEC(50)/E (max) (stimulation factor) of 9.16/5.5, 9.11/4.9 and 8.35/5.5, respectively. c[Cys(7,10)], N/OFQ(1-13)NH(2) and N/OFQ inhibited forskolin-stimulated cyclic adenosine monophosphate (cAMP) formation with pEC(50) values of 10.08, 10.11 and 9.78, respectively. All ligands produced complete inhibition of cAMP formation. In both functional assays, c[Cys(7,10)] was a full agonist. In a series of metabolism experiments, incubation of 1 nM c[Cys(7,10)], N/OFQ(1-13)NH(2) and N/OFQ with a rat brain homogenate produced a time-dependent loss of peptide that was greatest for the native peptide N/OFQ. Amidation in N/OFQ(1-13)NH(2) produced some metabolic protection, but this was not significantly improved by further inclusion of c[Cys(7,10)]. In summary, c[Cys(7,10)] is a high-affinity, high-potency full agonist of the NOP receptor. However, we were unable to demonstrate clear metabolic protection.

Estudo da população fraturada, devido a acidentes de trânsito, internada na Santa Casa de São Paulo

Introdução:Estudando uma população fraturada, percebemos grande incidência de acidentes de trânsito (AT), a segunda maior causa de morte no país, custando R$105 milhões ao governo por ano. Objetivo: Caracterizar a população fraturada em conseqüência de AT e averiguar associação deste com uso de álcool. Metodologia: 67 pacientes fraturados, de ambos os sexos, com idades entre 18 e 92 anos, preencheram a Ficha Sócio-Demográfica e o Protocolo de Avaliação Psicológica, em entrevistas nos leitos, com duração aproximada de 50 minutos. Resultados: 37,3 por cento são vítimas de AT, predominando acidentes de moto (17,9 por cento), sendo a proporção maior de homens em 2:1. Da amostra, 44,8 por cento refere uso atual de álcool. Nesta população que utiliza álcool, 63,3 por cento possuem entre 18 e 32 anos e 35 por cento destes jovens envolveram-se em acidentes. Conclusão: A prevalência de AT na população masculina jovem é correlacionada com a idade, uso atual de álcool e aumento do número de trabalhadores com moto.(AU)

Introduction: Among the fractured population, there is high incidence of traffic accident (TA), the second biggest death cause in the country, which expenses to the government represents R$105 million. Objective: To characterize the fractured population in consequence of TA and to verify the association of TA with alcohol use. Methods: 67 fractured patients, both genders, ages between 18 and 92, fulfilled the Social-Demographic File Card and the Psychological Evaluation Protocol through interviews with 50 minutes length realized at the hospital bed. Results: 37,3 percent are TA victims, mainly motorcycle accidents (17,9 percent), with prevalence of male gender of 2:1. In the sample, 44,8 percent reports current alcohol consumption. Among the population which ingests alcohol, 63,3 percent are 18 to 32 years old and 35 percent of these young sample have been involved in accidents. Conclusion: The prevalence of TA among young male population is related to age, current alcohol consumption and the increase of motorcycle-workers.(AU)

Pharmacological profile of the cyclic nociceptin/orphanin FQ analogues c[Cys10,14]N/OFQ(1-14)NH2 and c[Nphe1,Cys10,14]N/OFQ(1-14)NH2.

In this study we describe the activity of two cyclic nociceptin/orphanin FQ (N/OFQ) peptides; c[Cys(10,14)]N/OFQ(1-14)NH(2) (c[Cys(10,14)]) and its [Nphe(1)] derivative c[Nphe(1),Cys(10,14)]N/OFQ(1-14)NH(2) (c[Nphe(1),Cys(10,14)]) in native rat and mouse and recombinant human N/OFQ receptors (NOP). Cyclisation may protect the peptide from metabolic degradation. In competition binding studies of rat, mouse and human NOP the following rank order pK(i) was obtained: N/OFQ(1-13)NH(2)(reference agonist)>N/OFQ=c[Cys(10,14)]>>c[Nphe(1)Cys(10,14)]. In GTPgamma(35)S studies of Chinese hamster ovary cells expressing human NOP (CHO(hNOP)) c[Cys(10,14)] (pEC(50) 8.29) and N/OFQ(1-13)NH(2) (pEC(50) 8.57) were full agonists whilst c[Nphe(1)Cys(10,14)] alone was inactive. Following 30 min pre-incubation c[Nphe(1)Cys(10,14)] competitively antagonised the effects of N/OFQ(1-13)NH(2) with a pA(2) and slope factor of 6.92 and 1.01 respectively. In cAMP assays c[Cys(10,14)] (pEC(50) 9.29, E(max) 102% inhibition of the forskolin stimulated response), N/OFQ(1-13)NH(2) (pEC(50) 10.16, E(max) 103% inhibition) and c[Nphe(1)Cys(10,14)] (~80% inhibition at 10 microM) displayed agonist activity. In the mouse vas deferens c[Cys(10,14)] (pEC(50) 6.82, E(max) 89% inhibition of electrically evoked contractions) and N/OFQ(1-13)NH(2) (pEC(50) 7.47, E(max) 93% inhibition) were full agonists whilst c[Nphe(1)Cys(10,14)] alone was inactive. c[Nphe(1)Cys(10,14)] (10 microM) competitively antagonised the effects of N/OFQ(1-13)NH(2) with a pK(B) of 5.66. In a crude attempt to assess metabolic stability, c[Cys(10,14)] was incubated with rat brain membranes and then the supernatant assayed for remaining peptide. Following 60 min incubation 64% of the 1 nM added peptide was metabolised (compared with 54% for N/OFQ-NH(2)). In summary, we report that c[Cys(10,14)] is a full agonist with a small reduction in potency but no improvement in stability whilst c[Nphe(1)Cys(10,14)] displays tissue (antagonist in the vas deferens) and assay (antagonist in the GTPgamma(35)S assay and agonist in cAMP assay) dependent activity.

A marked decrease in bispectral index with elevation of suppression ratio by cervical haematoma reducing cerebral perfusion pressure.

A 77-year-old man with a ruptured abdominal aortic aneurysm undergoing aneurysmectomy were anaesthetised with ketamine under bispectral index (BIS) monitoring, which is a clinical EEG monitor for measurement of depth of anaesthesia/sedation. First marked BIS reduction with elevation of suppression ratio (SR) was observed following severe hypotension by deflation of the aortic occlusion balloon. The re-inflation and rapid blood transfusion improved haemodyanamics and BIS and SR. At second marked BIS reduction with SR elevation, a heavy cervical swelling due to a massive subcutaneous haematoma around the previously mis-punctured right carotid artery extending throughout the whole neck was observed without hypotension. Cervical relief incision improved the BIS and SR. The present case suggests that BIS monitor may be a simple and convenient monitor for cerebral ischaemia detection.

Effects of nicardipine and diltiazem on the bispectral index and 95% spectral edge frequency.

BACKGROUND AND OBJECTIVE: Previous studies have shown that L-type voltage-sensitive Ca2+ channel blocking agents increased and the L-type Ca2+ channel activator Bay K 8644 reduced the general anaesthetic potency in animals. As the bispectral index correlates with the depth of sedation, we examined whether L-type Ca2+ channel blocking agents affect the bispectral index. METHODS: Thirty hypertensive patients (systolic arterial pressure >160 mmHg) presenting for total intravenous anaesthesia with propofol, fentanyl and ketamine were recruited. Bispectral index monitoring was commenced directly the patients arrived in the operating theatre. All patients were given either nicardipine or diltiazem intravenously at the discretion of the anaesthesiologist in charge. RESULTS: Twenty-three and seven patients received nicardipine or diltiazem, respectively. The bispectral index level (mean (95% confidence interval)) did not change with either drug. In the nicardipine group, the bispectral index at 0, 5, 10 and 15 min was 55 (52-58), 55 (51-59), 55 (52-59) and 56 (53-59), respectively. In the diltiazem group, values were 59 (48-71), 60 (51-70), 61 (52-71) and 61 (50-72), respectively. Both L-type Ca2+ channel blocking agents significantly decreased arterial pressure. CONCLUSIONS: Clinical doses of nicardipine and diltiazem do not alter the bispectral index during general anaesthesia.

Preoperative intradermal acupuncture reduces postoperative pain, nausea and vomiting, analgesic requirement, and sympathoadrenal responses.

BACKGROUND: In a controlled and double-blind study, the authors tested the hypothesis that preoperative insertion of intradermal needles at acupoints 2.5 cm from the spinal vertebrae (bladder meridian) provide satisfactory postoperative analgesia. METHODS: The authors enrolled patients scheduled for elective upper and lower abdominal surgery. Before anesthesia, patients undergoing each type of surgery were randomly assigned to one of two groups: acupuncture (n = 50 and n = 39 for upper and lower abdominal surgery, respectively) or control (n = 48 and n = 38 for upper and lower abdominal surgery, respectively). In the acupuncture group, intradermal needles were inserted to the left and right of bladder meridian 18-24 and 20-26 in upper and lower abdominal surgery before induction of anesthesia, respectively. Postoperative analgesia was maintained with epidural morphine and bolus doses of intravenous morphine. Consumption of intravenous morphine was recorded. Incisional pain at rest and during coughing and deep visceral pain were recorded during recovery and for 4 days thereafter on a four-point verbal rating scale. We also evaluated time-dependent changes in plasma concentrations of cortisol and catecholamines. RESULTS: Starting from the recovery room, intradermal acupuncture increased the fraction of patients with good pain relief as compared with the control (P < 0.05). Consumption of supplemental intravenous morphine was reduced 50%, and the incidence of postoperative nausea was reduced 20-30% in the acupuncture patients who had undergone either upper or lower abdominal surgery (P < 0.01). Plasma cortisol and epinephrine concentrations were reduced 30-50% in the acupuncture group during recovery and on the first postoperative day (P < 0.01). CONCLUSION: Preoperative insertion of intradermal needles reduces postoperative pain, the analgesic requirement, and opioid-related side effects after both upper and lower abdominal surgery. Acupuncture analgesia also reduces the activation of the sympathoadrenal system that normally accompanies surgery.

[Changes in serum malondialdehyde-modified low-density lipoprotein in patients with acute myocardial infarction and stable angina pectoris treated by coronary angioplasty].

OBJECTIVES: Serum malondialdehyde-modified low-density lipoprotein(MDA-LDL) was measured as a marker of oxidative stress, and the changes in serum MDA-LDL compared in patients with acute myocardial infarction and stable angina pectoris treated by percutaneous transluminal coronary angioplasty (PTCA). METHODS: Forty-one patients with acute myocardial infarction or stable angina pectoris were admitted to our hospitals between January 2000 and June 2000. Direct PTCA was performed in 17 patients(MI group) and elective PTCA in 24 patients(AP group). Coronary angiography was performed in nine control subjects(control group). Serum MDA-LDL was measured in the peripheral venous blood before and immediately after procedures in each group(normal range 20-80 U/l). RESULTS: There were no significant differences in patient characteristics, except age, between the MI group and AP group. Serum MDA-LDL was elevated above the normal range before the procedure in both groups(MI group 104.7 +/- 52.0 U/l, AP group 99.7 +/- 42.8 U/l), and significantly decreased immediately after the procedure(MI group 61.3 +/- 25.6 U/l, AP group 62.0 +/- 29.6 U/l), but there were no significant differences between the two groups. Serum MDA-LDL was elevated before the procedure (99.3 +/- 48.9 U/l) in the control group and significantly decreased immediately after the procedure(61.7 +/- 26.2 U/l). However, these values did not differ from the values before and immediately after the procedure in the MI group and the AP group. The percentage changes in serum MDA-LDL before and immediately after the procedure were -38 +/- 16% in the MI group, -37 +/- 17% in the AP group and -36 +/- 20% in the control group, and there were no significant differences between the three groups. CONCLUSIONS: No significant difference in the changes in serum MDA-LDL was observed between patients with acute myocardial infarction and stable angina pectoris treated by PTCA. However, anticoagulants may affect the MDA-LDL measurements directly, because similar changes in serum MDA-LDL were observed in control subjects after only coronary angiography.

Unilateral spatial neglect associated with chronic subdural haematoma: a case report.

A 69-year-old right-handed man who exhibited unilateral spatial neglect in association with a chronic subdural haematoma, presented with mild left arm and leg weakness first noted 4 weeks prior to admission. Neurologic examination on admission revealed a mild left hemiparesis, including the face. Neuropsychologic examination revealed left unilateral spatial neglect, but no language disturbance. Minimal support was necessary to maintain activities of daily living. Computed tomography revealed a large right temporoparietal, extraaxial hypodense fluid collection containing scattered hypodense foci. The haematoma was evacuated via a right parietal burr hole. Following surgery, the patient dramatically improved neurologically and neuropsychologically, as well as in independent performance of daily activities. It is suggested that the improvement in ADL provides a behavioural correlate of improvement in the latter, represented a behavioural correlate of improved cerebral function, and that either direct compression by the chronic subdural haematoma or an interhemispheric pressure difference had caused unilateral spatial neglect. Such neglect is an unusual consequence of chronic subdural haematoma.

Origin of Ca2+ necessary for carbachol-induced contraction in longitudinal muscle of the proximal colon of rats.

The origin of Ca2+ necessary for carbachol (CCh)-induced contraction of longitudinal muscle of the proximal colon of rats was studied. CCh induced contraction of the muscle consisting of two phases, phasic and tonic phases, with a concomitant biphasic increase in [Ca2+]i. After removal of Ca2+ from the bathing solution of the colonic segments, CCh-induced contraction was rapidly inhibited; there was almost complete inhibition 1 min after the removal. Nicardipine, a blocker of voltage-dependent calcium channel, also significantly inhibited CCh-induced contraction. On the other hand, treatment of the colonic segments with thapsigargin, an inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPase, did not significantly affect the contraction except causing a slight decrease in the rate of contraction. These results suggest that Ca> entering through voltage-dependent calcium channels, but not released from SR, is essential for CCh-induced contraction of longitudinal muscle of the proximal colon of rats. This strict dependency of the CCh-induced contraction on extracellular Ca2+ was discussed in relation to the results obtained in the fundus of rats.

Co-induction of heme oxygenase-1 and peroxiredoxin I in astrocytes and microglia around hemorrhagic region in the rat brain.

Heme[none1] oxygenase-1 (HO-1) and peroxiredoxin I (PrxI) are known to be oxidative stress- and heme-related proteins. The antioxidant activity of PrxI is inhibited by heme, therefore co-expression of HO-1 and PrxI is considered to be a reasonable mechanism to maintain its antioxidative function. Immunoblotting demonstrated that HO-1 and PrxI were induced around the hemorrhagic region. Immunohistochemical studies revealed that, in acute phase, HO-1 and PrxI were induced primarily in microglia. In the subacute and chronic phase, the immunoreactivity of HO-1 and PrxI in astrocytes was the most intense. These data are the first to demonstrate co-induction of HO-1 and PrxI in the brain. Our results suggest that HO-1 and PrxI are localized in a similar manner to assure the antioxidant activity of PrxI under stress conditions associated with intracerebral hemorrhage.

Barbiturates inhibit K(+)-evoked noradrenaline and dopamine release from rat striatal slices--involvement of voltage sensitive Ca(2+) channels.

The cellular target site(s) for anaesthetic action remain unclear. In rat striatal slices we have previously demonstrated that K(+)-evoked noradrenaline (NA) and dopamine (DA) release is mediated predominantly via P/Q-type voltage sensitive Ca(2+) channels (VSCC). Using this model of Ca(2+) dependent transmitter release we have evaluated the effects of anaesthetic and non-anaesthetic barbiturates. Rat brain striatal slices were incubated in the absence and presence of barbiturate for 10 min at 37 degrees C. The slices were then incubated for 6 min with 40 mM KCl. All anaesthetic barbiturates produced a concentration-dependent inhibition of K(+)-evoked NA and DA release. Non-anaesthetic barbiturate, barbituric acid was ineffective. The pIC(50) for NA and DA release (thiopental: 4.90+/-0.13 and 5.00+/-0.10, pentobarbital: 4.39+/-0.07 and 4.43+/-0.14, phenobarbital: 3.85+/-0.08 and 3.59+/-0.10, respectively) correlated with lipid solubility (NA: r(2)=0.999, DA: r(2)=0.987). We therefore suggest that barbiturates inhibit catecholamine release via an interaction with P/Q VSCC further implicating this channel in anaesthetic action.