APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD).

PURPOSE: Inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be as low as 30% for frontotemporal dementia. Modifier genes could account for decreased frontotemporal dementia penetrance. In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. METHODS: From a database of 231 members of 15 families, 174 had APOE genotype available for analysis. Logistic regressions on APOE genotype and frontotemporal dementia were performed, using appropriate covariates. RESULTS AND CONCLUSION: FTD was associated with APOE 4 genotype (P=0.0002), myopathy (P=0.0006), and age (P=0.01), but not microtubule associated protein tau (MAPT) H2 haplotype (P=0.5) or gender (0.09) after adjustment for membership in pedigrees with at least one APOE 4 genotype. These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. The molecular basis of this link bears further investigation. We did not observe an association of frontotemporal dementia and H2 MAPT haplotype.     

Use of 3D reconstruction to correct for patient motion in SPECT

Patient motion occurring during data acquisition in single photon emission computed tomography (SPET) can cause serious reconstruction artefacts. We have developed a new approach to correct for head motion in brain SPECT. Prior to motion, projections are assigned to conventional projections. When head motion occurs, it is measured by a motion monitoring system, and subsequent projection data are mapped to 'virtual' projections. The appropriate position of each virtual projection is determined by applying the converse of the patient's accumulated motion to the actual camera projection. Conventional and virtual projections, taken together, form a consistent set that can be reconstructed using a three-dimensional (3D) algorithm. The technique has been tested on a range of simulated rotational movements, both within and out of the transaxial plane. For all simulated movements, the motion corrected images exhibited better agreement with a motion free reconstruction than did the uncorrected images. This technique may help to overcome one of the major remaining limitations on image quality and quantitative accuracy in SPECT.     

Mucosal pseudolipomatosis of the colon

Twenty-four cases of a lesion characterized by unlined spaces in the colorectal lamina propria are presented. While lesions such as this have been reported previously as "lipomatosis" of the colon, histochemical and ultrastructural examination reveals that they are not, in fact, composed of adipocytes. It appears that they may be composed of gas trapped in the lamina propria. Because of their gross and microscopical similarity to fat, however, the term "pseudolipomatosis" is proposed.     

Clinical neurophysiology of dementia

The role of EEG in the study of the dementias is to help in the differential diagnosis of the multiple causes of this syndrome. EEG is useful in differentiating early on between treatable and as of now untreatable forms of dementia. Space-occupying lesions that give rise to dementia are reliably detected by EEG. Infectious, toxic, and metabolic processes are associated with early and severe electroencephalographic abnormalities. The "slow virus" infections show characteristic electrical patterns that reliably distinguish them from the cortical or subcortical dementias. Finally, the EEG may contribute to distinguishing between Alzheimer's disease and MID, two commonly occurring forms of dementia. The paucity of substantial early EEG abnormalities in Alzheimer's disease, although helping to differentiate it from other dementias, leaves us without a currently available physiologic test that provides positive evidence for this condition. Recent studies of EPs, however, suggest that some intermediate latency VEP components may be delayed in patients with Alzheimer's disease when compared with normal subjects. This is encouraging, as latencies in VEPs are more reliable and less variable than amplitude that has previously been reported as "abnormal" in some early Alzheimer patients. Long latency ERPs and CNV also show early abnormalities in Alzheimer's disease. Tests of eye movements such as ERPs are psychophysiologic tests requiring some degree of patient cooperation. Performance on tests of ocular smooth pursuit correlate highly with severity of the dementia syndrome in Alzheimer's disease. In contrast, smooth pursuit testing is usually normal in elderly patients with pseudodementia of depression, suggesting this test may be of some value in differentiating these two clinical disorders. Some evidence exists that smooth pursuit eye movements are also normal, at least in the early and middle stages, in Pick's disease, again suggesting that eye movement testing may prove to have some utility in differentiating this form of dementia from Alzheimer's disease. Ocular scanpaths are abnormal in dementia. They typically are poorly organized and at times perseveratory. In addition, the average durations of eye fixations during directed visual search are altered in dementia as compared with normals. The average eye fixation durations are longer with Alzheimer's disease and briefer in patients with frontal lobe tumors as compared with elderly normal controls. These group differences suggest differing scanning strategies for these two forms of dementia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of [3H]-BIDN,a novel bicyclic dinitrile radioligand for GABA-gated chloride channels of insects and vertebrates

1. The radiolabelled bicyclic dinitrile, [³H]-3,3-bis-trifluoromethyl-bicyclo[2.2.1]heptane-2,2-dicarbonitrile ([³H]-BIDN), exhibited, specific binding of high affinity to membranes of the southern corn rootworm (Diabrotica undecimpunctata howardi) and other insects. A variety of γ-aminobutyric acid (GABA) receptor convulsants, including the insecticides heptachlor (IC₅₀, 35±3 nM) and dieldrin (IC₅₀, 93±7 nM), displaced [³H]-BIDN from rootworm membranes. When tested at 100 μM, 1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]octane(EBOB), 4-t-butyl-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane-1-thione (TBPS), 1-phenyl-4-t-butyl-2,6,7-trioxabicyclo[2.2.2]octane (TBOB) and picrotoxin failed to displace 50% of [³H]-BIDN binding to rootworm membranes indicating that the bicyclic dinitrile radioligand probes a site distinct from those identified by other convulsant radioligands.
2. Dissociation studies showed that dieldrin, ketoendrin, toxaphene, heptachlor epoxide and α and β endosulphan displace bound [³H]-BIDN from rootworm membranes by a competitive mechanism.
3. Rat brain membranes were also shown to possess a population of saturable, specific [³H]-BIDN binding sites, though of lower affinity than in rootworm and with a different pharmacological profile. Of the insecticidal GABAergic convulsants that displaced [³H]-BIDN from rootworm, cockroach (Periplaneta americana) and rat brain membranes, many were more effective in rootworm.
4. Functional GABA-gated chloride channels of rootworm nervous system and of cockroach nerve and muscle were blocked by BIDN, whereas cockroach neuronal GABA_B receptors were unaffected.
5. Expression in Xenopus oocytes of either rat brain mRNA, or cDNA-derived RNA encoding a GABA receptor subunit (Rdl) that is expressed widely in the nervous system of Drosophila melanogaster resulted in functional, homo-oligomeric GABA receptors that were blocked by BIDN. Thus, BIDN probes a novel site on GABA-gated Cl⁻ channels to which a number of insecticidally-active molecules bind.

     

Symptomatic pulmonary complications from liquid acrylate embolization of brain arteriovenous malformations.

PURPOSETo describe symptomatic pulmonary emboli from brain arteriovenous malformation embolization with liquid acrylates and to analyze the reasons for these complications and describe preventive techniques.METHODSThe clinical records of 182 patients embolized with acrylate glue since 1978 for treatment of brain AVMs were searched for evidence of symptomatic pulmonary complications. Originally iso-butyl-2-cyanoacrylate and more recently n-butyl-2-cyanoacrylate were used in all patients. Arteriovenous malformation morphology, amounts and techniques of glue injection, and clinical and radiologic investigations in the symptomatic patients were recorded.RESULTSThree patients had pulmonary symptoms within 48 hours of glue injection. One patient with a left frontal arteriovenous malformation had embolization with an isobutyl-2-cyanoacrylate/pantopaque/acetic acid mixture; severe pleuritic chest pain developed 2 days later. One patient with a left temporal and one with a left cerebellar arteriovenous malformation had embolization with n-butyl-2-cyanoacrylate/lipiodol mixtures; a cough, pleuritic chest pain, and bloody sputum developed in both within 24 hours. Two patients experienced a significant drop in PO2. No flow-arrest techniques were used for any of the injections in these three patients. All patients demonstrated significant changes on chest x-ray and CT chest examinations. All were treated conservatively and recovered spontaneously.CONCLUSIONSSymptomatic pulmonary complications can occur after acrylate glue injection, particularly when delivery systems without flow arrest are used in high-flow vascular brain lesions. Techniques using acetic acid to delay polymerization time and "sandwich" techniques in which glue is pushed with dextrose are also more susceptible to this complication.