EEG in Creutzfeldt-Jakob disease.

Electroecenphalography (EEG) is an integral part of the diagnostic process in patients with Creutzfeldt-Jakob disease (CJD). The EEG has therefore been included in the World Health Organisation diagnostic classification criteria of CJD. In sporadic CJD (sCJD), the EEG exhibits characteristic changes depending on the stage of the disease, ranging from nonspecific findings such as diffuse slowing and frontal rhythmic delta activity (FIRDA) in early stages to disease-typical periodic sharp wave complexes (PSWC) in middle and late stages to areactive coma traces or even alpha coma in preterminal EEG recordings. PSWC, either lateralized (in earlier stages) or generalized, occur in about two-thirds of patients with sCJD, with a positive predictive value of 95%. PSWC occur in patients with methionine homozygosity and methionine/valine heterozygosity but only rarely in patients with valine homozygosity at codon 129 of the prion protein gene. PSWC tend to disappear during sleep and may be attenuated by sedative medication and external stimulation. Seizures are an uncommon finding, occurring in less than 15% of patients with sCJD. In patients with iatrogenic CJD, PSWC usually present with more regional EEG findings corresponding to the site of inoculation of the transmissible agent. In genetic CJD, PSWC in its typical form are uncommon, occurring in about 10%. No PSWC occur in EEG recordings of patients with variant CJD.     

Rostral anterior cingulate cortex activity in the theta band predicts response to antidepressive medication.

During the last 10 years the knowledge about rostral anterior cingulate cortex (ACC) activity in major depression has substantially increased. Several groups have independently described a relationship between resting activity in this area and response to antidepressant treatment. We have recently confirmed a relationship between resting activity of rostral ACC activity and response in a group of 20 patients with major depression using resting theta activity. In this earlier study regions of interest (ROI) were defined in order to establish regional specificity. Differences between responders and nonresponders were only found in the ACC-ROI, but not in the posterior cingulate region. We have now reanalyzed our data using a whole brain voxelwise approach, in order not to miss any other relevant functional differences. In addition to major differences between responders and nonresponders in the rostral ACC, we have identified a nearby region in the midline orbito-frontal region.     

Freezing of gait in postmortem-confirmed atypical parkinsonism.

The frequency and pathophysiology of freezing of gait (FoG) in atypical parkinsonism is unknown. We analysed the frequency of FoG in postmortem-confirmed atypical parkinsonian disorders (APD) comprising corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Sixty-six patients with pathologically confirmed APD (CBD, n = 13; DLB, n = 14; MSA, n = 15; PSP, n = 24) formed the basis for a multicenter clinicopathological study. Clinical features at first and last clinical visit were abstracted from patient records on standardized forms following strict instructions. At the first visit (median 36 months after symptom onset), 24% of APD had FoG (CBD, 8%; DLB, 21%; PSP, 25%; MSA, 40%). Logistic regression analysis showed a significant association of FoG and urinary incontinence (P = 0.04) at first visit. At last visit, 47% of APD had FoG (CBD, 25%; PSP, 53%; DLB, 54%; MSA, 54%). Clinicopathological correlation based on routine postmortem examination failed to identify a consistent neuropathological substrate of FoG. This study demonstrates that (1) FoG is common in APD, and (2) urinary incontinence is significantly associated with FoG in these disorders. Whether FoG and urinary incontinence share similar neuropathological substrates remains to be determined by future studies.     

Studies on Propafenone-type Modulators of Multidrug-Resistance IV: Synthesis and Pharmacological Activity of 5-Hydroxy and 5-Benzyloxy Derivatives

A series of 5-hydroxy and 5-benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR-modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3 . Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a–d . Subsequent cleavage of the benzyl group gave the 5-hydroxy analogs 6a–d . Structure activity relationship studies showed, that the 5-hydroxy derivates 6a–d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5-benzyloxy analogs 5a–d showed almost identical EC₅₀ values, independent of their log P value.     

Electro-encephalographic disturbances due to chronic toxin abuse in young people, with special reference to glue-sniffing

A study was carried out in order to document any abnormalities in the electro-encephalogram (EEG) that might appear in young adolescents who have deliberately inhaled the range of volatile substances loosely referred to as 'glue'. The EEGs of a group of 'street children' being assisted in a Johannesburg shelter were examined. The records were analysed for any clinical abnormalities and also subjected to spectral analysis in order to examine the overall characteristics of frequency, power and spatial distribution. The EEGs clearly revealed that, although at the time of the examination the subjects were ostensibly abstinent, both clinical and normative evidence of continuing brain disturbance was present. It was concluded that glue sniffing is likely to have long term electrocerebral sequelae.     

5-HT-receptor-induced changes of the intracellular cAMP level monitored by a hyperpolarization-activated cation channel

The HvCNG channel from the moth Heliothis virescens is highly sensitive to cAMP concentrations ranging between 0.1 microM and 5 microM. This HvCNG channel was over-expressed in Spodoptera frugiperda (Sf.9) cells to measure endogenous cAMP levels. Hyperpolarization-activated inward currents were measured in the whole-cell patch-clamp configuration with pipettes filled with different cAMP concentrations to calibrate the system. Varying the cAMP concentration between 0 microM and 100 microM in the pipette, the half-maximal activation voltage ( V1/2) was shifted by +28.5+/-1.7 mV. The activation time constant (tau(a)) was used as a parameter for cAMP quantification because it was independent of the expression level of HvCNG channels. tau(a) changed from 1106+/-60 ms at 0 microM cAMP to 265+/-7 ms at a saturating concentration of 1 mM cAMP. A dose-response relationship yielded values of 0.6 microM for the half-maximal cAMP concentration and 1.5 for the Hill coefficient. Activation of endogenous adenylyl cyclases by 50 microM forskolin induced an elevation of the cAMP level by about 1.6+/-0.2 microM. Co-expressions of HvCNG channels in combination with the mouse 5-HT4a- or 5-HT1A- receptors and the corresponding Gs- or Gi-proteins were successful and allowed us to also verify receptor-induced changes of the cAMP level. Stimulation of m5-HT4a-receptors by 0.1 microM 5-HT induced an increase of cAMP of about 4.6+/-1.5 microM, whereas cAMP levels decreased from a control value of 1+/-0.2 microM to 0.41+/-0.1 microM after stimulation of the m5-HT1A-receptors.     

Diagnostik des Synovialsarkoms Simultane t(X;18) FISH- und SYT/SSX-RT-PCR-Analyse

Synovialsarkome sind mitunter schwierig von anderen Spindelzellsarkomen zu unterscheiden. In diesen Fällen kann der Nachweis einer t(X;18) Translokation unter Verwendung der FISH und RT-PCR helfen. Die vorliegende Arbeit wurde unter der Fragestellung durchgeführt, ob bei Synovialsarkom-verdächtigen Tumoren der simultane Einsatz beider Methoden zum Translokationsnachweis erforderlich ist oder ob eine der Methoden ausreicht.In die Studie wurde Paraffin-eingebettetes Tumorgewebe von 53 Patienten einbezogen, bei denen nach Lichtmikroskopie und Immunhistochemie der Verdacht auf das Vorliegen eines Synovialsarkoms bestand. Es erfolgte der Nachweis von t(X;18) mittels FISH und RT-PCR.     

Resource implications for a population-based colorectal cancer screening program in Canada: a study of the impact on colonoscopy capacity and costs in London, Ontario.

OBJECTIVE: Cancer Care Ontario has recommended a population-based colorectal cancer (CRC) screening program using fecal occult blood testing. Patients who test positive should undergo further investigation, preferably colonoscopy. So far, no studies have been performed to quantify the costs or demands on the health care system at the community level. The number of consultations, colonoscopies and polypectomies, and the corresponding direct medical costs generated by the CRC screening program, between 2006 and 2015 in London, Ontario, were estimated using a decision analysis model in comparison with the population health model. METHODS: A faxed survey study was conducted to examine the current CRC screening practice among family physicians in London. Data from the survey and randomized studies were applied to a decision analysis model, which simulated the steps involved in population-based biennial and annual CRC screening between 2006 and 2015. The number of consultations, colonoscopies and polypectomies, and their associated costs were calculated. RESULTS: For a cohort population of 140,000, between 50 and 74 years of age, in 2006 to 2015, it is estimated that an average of 412 consultations, 463 colonoscopies and 174 polypectomies will be performed per 100,000 screen eligible population per year in biennial screening, and double in annual screening, reflecting an average of 8.7% or 17.6% increase annually in outpatient colonoscopies, respectively, compared with 2003. A mean of $285,000 or $562,000 per year would be required to support the extra consultation and endoscopic procedures generated by the biennial or annual screening. CONCLUSION: Population-based fecal occult blood testing screening for CRC appears to be a manageable strategy if a modest increase in endoscopic resources is allocated.