Saturation analysis of specific 11C Ro 15-1788 binding to the human neocortex using positron emission tomography

The ¹¹C-labelled benzodiazepine antagonist Ro 15–1788 (flumazenil) and positron emission tomography (PET) were used to determine quantitative characteristics of benzodiazepine receptor binding in the neocortex of healthy young men. Saturating doses of unlabelled flumazenil administered i.v., before or together with the ligand-reduced ¹¹C-flumazenil accumulation in the neocortex by about 90 per cent. Saturating doses of unlabelled flumazenil had little effect on the accumulation of radioactivity in the benzodiazepine receptor-poor regions such as pons or white matter. By giving graded doses of unlabelled flumazenil together with the tracer, saturation isotherms were obtained allowing the calculation of receptor density (B_max) and equilibrium dissociation constant (K_d) values on the basis of certain assumptions B_max values were in the order of 90 pmol/g and K_d values in the order of 10 nM in the neocortex. Scatchard and Hill plots of the radioactivity data indicated that ¹¹C-flumazenil binds to saturable sites of a homogeneous population. The data indicate that intravenous doses of 1 or 2 mg flumazenil result in a benzodiazepine receptor occupancy of about 50 per cent. The method described should be useful for studying regional differences in benzodiazepine receptor characteristics in the living human brain in healthy subjects and neuropsychiatric disorders, and also in relation to treatment with drugs interacting with benzodiazepine receptors.     

Diagnosis of scaphoid fractures:A prospective multicenter study of 1,052 patients with 160 fractures

In a prospective multicenter study of 1,052 patients with clinical signs of a scaphoid fracture, mammo-graphic films and fine intensifying screens were used at the radiographic examination. 5 standardized projections including 3 special projections focused on the scaphoid were taken. 150 fractures were diagnosed at the first examination but in 10 cases the fracture was first diagnosed at a second radiographic examination after 10-14 days.

The second examination still seems mandatory despite the use of high quality radiographs with optimal spatial resolution and contrast, and the value of supplementary special projections.     

Cyclosporin A-induced remission of primary membranous glomerulonephritis in a child

Sir, A 4-year-old boy presented with oedema and weight gain of 5kg. There had been no preceding infections, vaccinations ormedication. The family history includes the mothers mesangioproliferativeglomerulonephritis. Laboratory results showed decreased albumin (13 g/l) concentration.Calculated glomerular filtration rate was 125 ml/min/1.73 m²and the     

Hydrodynamic aspects of pyelocalyceal peristalsis

This study was undertaken to determine the nature of pressure changes in manometric studies of renal pelvis and calyces. In previous studies in pigs it has been assumed that pressure increases occur in the contracting segments of the renal pelvis and calyces, but our observations suggested that these increases were actually due to distension of noncontracted segments. Pressures were recorded with two catheters introduced percutaneously into the pyelocalyceal system with simultaneous video recording of the fluoroscopic image. There was no pressure rise in the calyces or the renal pelvis when these segments contracted; however, pressure rose when the noncontracted calyces were distended by a remote contraction ring. These findings confirmed the observations at kinetic urography. They agreed with the hydrodynamic experience that the pressure in a ring-shaped contracted segment is lower than upstream and downstream of that segment. It was concluded that if the porcine pyelocalyceal system is a valid model of the human, the pressure increases, assumed to be contractions, were actually caused by the injection and distension of the noncontracted segments.     

Children with deficits in attention,motor control and perception (DAMP) almost grown up: The contribution of various background factors to outcome at age 16 years

Fifty-six children with and forty-five children without deficits in attention, motor control and perception (DAMP) had been recruited from the general population at age 7 years. They were followed up neuropsychiatrically at age 16 years after intermediate term follow up at age 10 and 13 years. Cases were subdivided into those with good and not good outcome on the basis of absence or presence of psychiatric and personality disorders, multiple traumatic accidents and speech and language problems at age 16 years. The presence of DAMP in itself was the strongest predictor of poor outcome. High scores for minor neurological dysfunction, low performance IQ, autistic features at age 7 years and poor reading skills at age 10 and/or 13 years were important background factors in cases with poor outcome. In the small subgroup with poor outcome among those without DAMP at age 7 years, major life events was the most important background factor.

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Zusammenfassung 56 Kinder mit und 45 Kinder ohne Störungen der Aufmerksamkeit, der motorischen Kontrolle und der Wahrnehmung (DAMP) waren aus einer Gesamtpopulation 7jÄhriger rekrutiert worden. Sie wurden neuropsychiatrisch im Alter von 16 jahren nachuntersucht, nachdem zwischenzeitliche Untersuchungen im Alter von 10 und 13 Jahren erfolgt waren. Die Probanden wurden in solche mit gutem und nicht gutem Ausgang unterteilt, in AbhÄngigkeit vom Vorliegen psychiatrischer AuffÄlligkeiten, Persönlichkeitsstörungen, multiplen Traumata und Sprech- und Sprachproblemen im Alter von 16 Jahren. Das Vorhandensein von DAMP war der stÄrkste PrÄdiktor für einen schlechten Ausgang. Hohe Werte für leichte neurologische AuffÄlligkeiten, ein niedriger Handlungs-IQ, autistische Züge im Alter von 7 Jahren und schlechte LesefÄhigkeiten im Alter von 10 und/oder 13 Jahren waren wichtige Hintergrundfaktoren bei den Probanden mit einem schlechten Ausgang. In der kleinen Untergruppe mit einem schlechten Ausgang bei den Kindern, die im Alter von 7 Jahren kein DAMP ausgewiesen hatten, bildeten schwerwiegende Lebensereignisse den wichtigsten Hintergrundfaktor.

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Résumé Cinquante-six enfants atteints et quarante-cinq enfants non atteints de déficits de l'attention, du contrÔle moteur et de la perception (DAMP), ont été recrutés en population générale à l'âge de 7 ans. Ils ont été évalués sur la plan neuropsychiatrique à l'âge de 16 ans, après des évaluations intermédiaires à l'âge de 10 et 13 ans. Les cas ont été subdivisés entre bons et mauvais devenir sur la base de la présence ou de l'absence de troubles de la personnalité, l'importance du nombre d'accidents traumatiques, les difficultés d'élocution et de langage à 16 ans. La présence de DAMP était en soi, le facteur prédictif le plus important de mauvais devenir. Des scores élevés à des dysfonctionnements neurologiques mineurs, un QI bas, des traits autistiques à l'âge de 7 ans, et de mauvaises capacités en lecture à l'âge de 10 ou 13 ans ont été des facteurs importants dans les cas de mauvais devenir. Dans le petit sous-groupe à mauvais devenir caractérisé par une absence de DAMP à l'âge de 7 ans, des événements de vie marquants ont semblé Être des antécédents importants.

     

Characterisation of Dopamine and Serotonin Uptake Inhibitory Effects of Tetrahydroaminoacridine in Rat Brain

Abstract: The effects of 1,2,3,4-tetrahydro-9-aminoacridine (THA) on uptake rates of radioactive 5-hydroxytryptamine (5-HT) and dopamine were investigated in rat diencephalon and striatal homogenates, respectively. Six and eight μM of THA were needed to inhibit 50% of dopamine and 5-HT uptake rates. Kinetic parameters, K_m and V_max, using six different concentrations of dopamine and 5-HT were estimated in the presence or absence of THA. A significant decrease in V_max without any change in K_m values was observed for both dopamine and 5-HT in the presence of THA. The results show that THA is a non-competitive uptake inhibitor of dopamine and 5-HT in the nerve terminals. The re-uptake blocking effect of THA on dopaminergic and serotonergic neurones, following THA treatment, might lead to increased levels of these monoamines in brains of Alzheimer patients and contribute in the therapeutic effects of the drug.     

Wilson's disease tremor is associated with magnetic resonance imaging lesions in basal ganglia structures.

Wilson's disease (WD) is an inherited disorder of copper metabolism yielding marked motor deficits, including a severely disabling tremor. As a structural correlate of the disease, a variety of cerebral abnormalities has been revealed. However, the relationship between motor deficits and cerebral lesions has remained largely unknown. Here, we investigated correlation between WD tremor and cerebral magnetic resonance imaging (MRI) findings. Cerebral MRI abnormalities in 6 symptomatic WD patients were compared to findings in 6 asymptomatic WD patients and 10 healthy controls. All patients were treated with long-term copper chelating therapy. Motor symptoms including tremor were determined by Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). MRI findings in symptomatic WD patients revealed significant symmetric T2*-weighted hypointense signal alterations of globus pallidus, head of the caudate nucleus, and substantia nigra. In contrast, MRI of asymptomatic WD patients did not differ from healthy controls. Correlation analysis revealed a significant positive correlation between MRI basal ganglia lesions and UPDRS action tremor score. Our results demonstrate for the first time that Wilson's disease tremor is associated with lesions of the globus pallidus, the head of the caudate nucleus, and the substantia nigra.     

Capillary-oxygenation-level-dependent near-infrared spectrometry in frontal lobe of humans.

Brain function requires oxygen and maintenance of brain capillary oxygenation is important. We evaluated how faithfully frontal lobe near-infrared spectroscopy (NIRS) follows haemoglobin saturation (SCap) and how calculated mitochondrial oxygen tension (PMitoO2) influences motor performance. Twelve healthy subjects (20 to 29 years), supine and seated, inhaled O2 air-mixtures (10% to 100%) with and without added 5% carbon dioxide and during hyperventilation. Two measures of frontal lobe oxygenation by NIRS (NIRO-200 and INVOS) were compared with capillary oxygen saturation (SCap) as calculated from the O2 content of brachial arterial and right internal jugular venous blood. At control SCap (78%+/-4%; mean+/-s.d.) was halfway between the arterial (98%+/-1%) and jugular venous oxygenation (SvO2; 61%+/-6%). Both NIRS devices monitored SCap (P<0.001) within approximately 5% as SvO2 increased from 39%+/-5% to 79%+/-7% with an increase in the transcranial ultrasound Doppler determined middle cerebral artery flow velocity from 29+/-8 to 65+/-15 cm/sec. When SCap fell below approximately 70% with reduced flow and inspired oxygen tension, PMitoO2 decreased (P<0.001) and brain lactate release increased concomitantly (P<0.001). Handgrip strength correlated with the measured (NIRS) and calculated capillary oxygenation values as well as with PMitoO2 (r>0.74; P<0.05). These results show that NIRS is an adequate cerebral capillary-oxygenation-level-dependent (COLD) measure during manipulation of cerebral blood flow or inspired oxygen tension, or both, and suggest that motor performance correlates with the frontal lobe COLD signal.     

Longitudinal analysis of the relation between moderate long‐term stress and health

The main goal of the present work was to longitudinally examine consequences of long‐term moderately elevated levels of stress for various health outcomes. To address this issue, data covering 10 years was used from the ongoing Swedish population‐based prospective Betula Study. Based on the ratings on a validated self‐reported stress scale, matched subsamples between 40 and 65 years of age were divided into a high (n = 137) and low (n = 211) stress group. The reported incidence of cardiovascular, diabetes, psychiatric, tumour and musculoskeletal diseases was assessed 5 and 10 years after baseline (baseline = 1993–1995) without contaminating effects of past health history. The incidence of diseases 5 years after baseline assessment showed no differences between the groups. After 10 years, there was a significantly higher incidence of psychiatric diseases, mainly depression in the high‐stress group as well as a significant effect for tumours, although the number of cases was low. Although moderately elevated stress level may have a possible impact on psychiatric diseases especially depression and some tumours, it seems that prolonged moderate stress does not appear to be harmful to other stress‐related diseases. Copyright © 2007 John Wiley & Sons, Ltd.