Brain serotonin transporter binding in non-depressed patients with Parkinson's disease

Early post-mortem data suggest that damage to brain serotonin neurones might play a role in some features (e.g., depression) of Parkinson's disease (PD). However, it is not known whether such damage is a typical characteristic of living patients with PD or whether the changes are regionally widespread. To address this question we measured, by positron emission tomography imaging, levels of the brain serotonin transporter (SERT), a marker for serotonin neurones, as inferred from binding of [¹¹C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB), a second generation SERT radioligand, in subcortical and cerebral cortical brain areas of clinically advanced non-depressed (confirmed by structured psychiatric interview) patients with PD. SERT binding levels in PD were lower than those in controls in all examined brain areas, with the changes statistically significant in orbitofrontal cortex (−22%), caudate (−30%), putamen (−26%), and midbrain (−29%). However, only a slight non-significant reduction (−7%) was observed in dorsolateral pre-frontal cortex, an area implicated in major depression. Our imaging data suggests that a modest, regionally widespread loss of brain serotonergic innervation might be a common feature of advanced PD. Further investigation will be required to establish whether SERT binding is more or less decreased in those patients with PD who also have major depressive disorder.     

The association of post-stroke neurological improvement with risk of subsequent deterioration due to stroke events

We sought to simultaneously confirm that substantial recovery at day 1 and day 7 after acute ischaemic stroke onset is associated with subsequent neurological deterioration in patients of the Acute Stroke Therapy by Inhibition of Neutrophils randomized clinical trial. Substantial recovery was assessed by improvement in the National Institutes of Health Stroke Score (NIHSS). Neurological deterioration was defined as any stroke event or NIHSS worsening from recovery assessment to day 90. After adjusting for age, t-PA and day 1 NIHSS, there was a non-significant tendency of substantial (pre-specified as 75%) recovery at day 1 to be associated with later deterioration [odds ratio (OR) 2.47; 95% CI, 0.95–6.50]. The corresponding OR for substantial (pre-defined as 65%) recovery at day 7 was 1.84 (0.85–3.96). Other thresholds for recovery were significantly associated with later deterioration: >50%, 80%, 90% and 100% for day 1 and >50%, 60%, 70%, 90% and 100% for day 7. The effect of recovery at day 1 was more important than that of later recovery. This study confirms the association between recovery and subsequent neurological deterioration and is the first to indicate the greater importance of acute recovery at day 1 in comparison with later recovery.     

Complement component C5a predicts restenosis after superficial femoral artery balloon angioplasty.

PURPOSE: To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS: C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS: Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION: Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The complement component C5a exerts strong chemotactic and proinflammatory effects. Enhanced complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of complement inhibition thus may be worth investigating with respect to improving patency rates.     

Vitamin D and the skin: new aspects and perspectives]

Vitamin D (calciferol) is under clinical investigation for the treatment of psoriasis. Vitamin D was previously solely regarded as a key substance in hormonal calcium homeostasis, a view that is no longer tenable. The human receptor for the biologically active metabolite 1,25-dihydroxyvitamin-D3 was cloned in 1988. Sequence analyses revealed that it was a member of the nuclear steroid hormone receptor family. This family of gene-regulatory DNA-binding proteins includes the oestrogen, progesterone, glucocorticoid, mineralocorticoid, thyroxine (T-3) and retinoic acid receptors. Vitamin D receptors have been identified in a variety of tissues primarily unrelated to calcium metabolism. The skin and the immune system are some of the most interesting new targets. In vitro 1,25-dihydroxyvitamin-D3 inhibits proliferation and induces differentiation of keratinocytes. Furthermore, this hormone has potent immunomodulatory functions.     

Ca2+/calmodulin-dependent protein phosphorylation is not altered by amygdaloid kindling

Kindling is a process in which episodic electrical stimulation permanently increases seizure susceptibility. One mechanism to account for a change in seizure susceptibility is some alteration in signal transduction, possibly at the level of second messenger systems. In this study, male Long-Evans rats were kindled in the amygdala, and Ca2+/calmodulin (Ca2+/CaM)-dependent protein phosphorylation was assessed at the site of the primary kindled focus using one- and two-dimensional gel electrophoresis. In vitro phosphorylation of membrane and cytosol fractions in the presence of absence of Ca2+/CaM did not differentiate kindled from nonkindled amygdaloid tissue. These results suggest that changes in Ca2+/CaM-dependent phosphorylation are not related to the mechanism(s) underlying the establishment of an amygdaloid kindled focus.     

Psychiatric disorders in the families of schizotypal subjects.

In a study of the families of 21 schizotypal patients, we found an increased morbidity risk for schizophrenia compared with that in the families of 21 nonschizotypal patients and 42 controls. The Axis I diagnoses did not influence the distribution of the morbidity risk in the families of the schizotypal patients. If the schizotypal subjects also had other personality disorders, the morbidity risk for schizophrenia among their relatives was lower, although not significantly.     

Inhibitory effects of powerline-frequency (60-Hz) magnetic fields on pentylenetetrazol-induced seizures and mortality in rats.

The possibility that exposure to powerline frequency (60-Hz) magnetic fields might affect the form or intensity of epileptic seizures, induced by administration of pentylenetetrazol (PTZ) in rats, was examined. Male adult rats were exposed to either 60-Hz magnetic fields with intensities of up to 1.85 gauss (185 microT) or to a sham field condition, for 1 h prior to injections of PTZ (45-75 mg/kg). The subsequent seizures were monitored and recorded on videotape and any subsequent mortalities were noted. Exposure to 60-Hz magnetic fields prior to administration of PTZ was found to significantly (P less than 0.005) reduce the lethality of the drug-induced seizures. The LD50 for the sham-exposed group was 65.88 mg/kg, whereas for the 60-Hz magnetic field-exposed rats, the LD50 was 85.33 mg/kg. In some experiments exposure to the 1.0 and 1.5 gauss magnetic fields also produced significant (P less than 0.05) reductions in seizure durations. These findings suggest that acute exposure to low intensity 60-Hz magnetic fields has an inhibitory effect on the lethality and expression of PTZ-induced seizures in rats. Some possible mechanisms, which could account for these observed effects of magnetic field exposure on seizures, are discussed.     

Die Oberkieferosteotomie in der Le-Fort-I-Ebene — ein weites Indikations-spektrum zur Korrektur verschiedener skelettaler Dysgnathien

Zusammenfassung Die Osteotomie des Oberkiefers in der Le-Fort-I-Ebene, die heute routinemäßig in der Down-fracture-Technik durchgeführt wird, hat die chirurgische Behandlung skelettaler Dysgnathien grundlegend verändert. Sie ermöglicht eine dreidimensionale Korrektur des Oberkiefers und damit des gesamten Gesichtsschädels. Darüber hinaus kann der Oberkieferzahnbogen, zusätzlich zu einer Verlagerung des gesamten Oberkiefers, durch eine zusätzliche sagittale und transversale Osteotomie erweitert, verschmälert und verkürzt werden. Die Planung einer Oberkieferosteotomie erfolgt anhand des klinischen Bildes, der Kiefermodelle und des Fernröntgenbildes. Dabei muß der Unterkiefer frühzeitig mit in die Planung einbezogen werden, da er durch die Autorotation im Gelenk den Verlagerungen des Oberkiefers folgt. Erst durch eine gleichzeitige Osteotomie auch des Unterkiefers ergibt sich ein weites Indikationsspektrum für die Oberkieferosteotomie. Bei einer kombinierten Ober- und Unterkieferosteotomie ist praktisch jedes gewünschte Profil im unteren Gesichtsdrittel erzielbar.

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Summary The osteotomy of the maxilla using the Le Fort I technique, today routinely performed in the down-fracture-technique, has changed surgical corrections of dentofacial deformities fundamentally. It offers a three-dimensional correction of the maxilla and also of the whole facial skull. Furthermore the upper dental arch can be expanded, intruded and shortened using a sagittal or transversal osteotomy in addition to a complete transposition of the maxilla. Planning of a maxillary osteotomy is performed under consideration of the clinical situation, the casts and the lateral cephalogram. The mandible must be considered at an early state of the preoperative planning, since the mandible will follow all transpositions of the maxilla by rotating with the TMJ. Only by performing a simultaneous osteotomy of the mandible, a broad spectrum of indications for maxillary osteotomy will result and practically every desired profile of the lower third of the face can be achieved using combined maxillary and mandibular osteotomies.