Comparison of PET, MRI, and CT with pathology in a proven case of Alzheimer's disease

Positron emission tomography (PET) with fluorodeoxyglucose (FDG), magnetic resonance imaging (MRI), and CT were carried out in a patient with Alzheimer's disease 16 months before he died. At autopsy, the gross appearance of the brain correlated with MRI and CT, which showed some regional atrophy. These were much less revealing than PET, which correlated with microscopic findings of neuronal loss and proliferation of glia. In areas of moderately impaired local cerebral metabolic rate of glucose, as revealed by reduced FDG uptake, there was some gliosis, primarily around the numerous senile plaques. In areas of severe metabolic impairment, there was a profound loss of neurons, extensive gliosis, and a diminished appearance of plaques. PET-FDG is a better measure of the severity of Alzheimer's disease than MRI or CT, because it reflects the degree of neuronal pathology.     

Laminar organization of the main olfactory bulb of Podarcis hispanica: an electron microscopic and Golgi study

In this study, the lamination pattern of the main olfactory bulb (MOB) of P. hispanica has been described using EM and Golgi-impregnation techniques. Six layers could be distinguished from the external surface to the ventricles: olfactory nerve layer (ONL), glomerular layer (GL), external plexiform layer (EPL), mitral layer (ML), internal plexiform layer (IPL), and granular cell layer (GCL). In ONL unmyelinated axonic bundles from the olfactory mucosa are seen. The GL is defined by the presence of terminal ramifications of the mitral primary dendrites and by axonic terminals of the olfactory nerve. The EPL is a dendritic articulation layer between the mitral and granule cells, where a great density of dendrodendritic synaptic contacts has been found. The ML is defined by the large mitral cell somata, and the IPL by myelinated axonic bundles that run rostro-caudally. Finally, the GCL is characterized by the presence of granule cells. Using the Golgi-impregnation method, five different neuronal types have been described. In the glomerular layer, a small cell population is located; these neurons seem the periglomerular cells described in mammals. The second type corresponds to the mitral cell population and the morphological features of these cells resemble to those of mammals. The three remaining types constitute the granule cell population; this population is characterized by a great morphological heterogeneousness. However, these types have been differentiated according to their dendritic tree morphology and location of the cell body. A morphological gradient depending on the distance of cell body for each type to the ependymal layer, has been observed. In EM, four different types of neuronal cell bodies according to their location and ultrastructure have been defined. The laminar organization of the MOB of Podarcis is similar to that in all vertebrates. The results for the fine structure and dendritic tree morphology have revealed a high similarity between these reptiles and mammals.     

Poisoning due to Pyrethroids

The first pyrethroid pesticide, allethrin, was identified in 1949. Allethrin and other pyrethroids with a basic cyclopropane carboxylic ester structure are type I pyrethroids. The insecticidal activity of these synthetic pyrethroids was enhanced further by the addition of a cyano group to give α-cyano (type II) pyrethroids, such as cypermethrin. The finding of insecticidal activity in a group of phenylacetic 3-phenoxybenzyl esters, which lacked the cyclopropane ring but contained the α-cyano group (and hence were type II pyrethroids) led to the development of fenvalerate and related compounds. All pyrethroids can exist as at least four stereoisomers, each with different biological activities. They are marketed as racemic mixtures or as single isomers. In commercial formulations, the activity of pyrethroids is usually enhanced by the addition of a synergist such as piperonyl butoxide, which inhibits metabolic degradation of the active ingredient. Pyrethroids are used widely as insecticides both in the home and commercially, and in medicine for the topical treatment of scabies and headlice. In tropical countries mosquito nets are commonly soaked in solutions of deltamethrin as part of antimalarial strategies. Pyrethroids are some 2250 times more toxic to insects than mammals because insects have increased sodium channel sensitivity, smaller body size and lower body temperature. In addition, mammals are protected by poor dermal absorption and rapid metabolism to non-toxic metabolites. The mechanisms by which pyrethroids alone are toxic are complex and become more complicated when they are co-formulated with either piperonyl butoxide or an organophosphorus insecticide, or both, as these compounds inhibit pyrethroid metabolism. The main effects of pyrethroids are on sodium and chloride channels. Pyrethroids modify the gating characteristics of voltage-sensitive sodium channels to delay their closure. A protracted sodium influx (referred to as a sodium ‘tail current’) ensues which, if it is sufficiently large and/or long, lowers the action potential threshold and causes repetitive firing; this may be the mechanism causing paraesthesiae. At high pyrethroid concentrations, the sodium tail current may be sufficiently great to prevent further action potential generation and ‘conduction block’ ensues. Only low pyrethroid concentrations are necessary to modify sensory neurone function. Type II pyrethroids also decrease chloride currents through voltage-dependent chloride channels and this action probably contributes the most to the features of poisoning with type II pyrethroids. At relatively high concentrations, pyrethroids can also act on GABA-gated chloride channels, which may be responsible for the seizures seen with severe type II poisoning. Despite their extensive world-wide use, there are relatively few reports of human pyrethroid poisoning. Less than ten deaths have been reported from ingestion or following occupational exposure. Occupationally, the main route of pyrethroid absorption is through the skin. Inhalation is much less important but increases when pyrethroids are used in confined spaces. The main adverse effect of dermal exposure is paraesthesiae, presumably due to hyperactivity of cutaneous sensory nerve fibres. The face is affected most commonly and the paraesthesiae are exacerbated by sensory stimulation such as heat, sunlight, scratching, sweating or the application of water. Pyrethroid ingestion gives rise within minutes to a sore throat, nausea, vomiting and abdominal pain. There may be mouth ulceration, increased secretions and/or dysphagia. Systemic effects occur 4–8 hours after exposure. Dizziness, headache and fatigue are common, and palpitations, chest tightness and blurred vision less frequent. Coma and convulsions are the principal life-threatening features. Most patients recover within 6 days, although there were seven fatalities among 573 cases in one series and one among 48 cases in another. Management is supportive. As paraesthesiae usually resolve in 12–24 hours, specific treatment is not generally required, although topical application of dl-α tocopherol acetate (vitamin E) may reduce their severity.     

Nails in systemic disease

Nail plate and nail unit abnormalities may be helpful as diagnostic tools or as a part of the puzzle for confirmation of systemic disease. There are specific and nonspecific nail signs, which can be seen involving one or more nails, that occur simultaneously or secondary to systemic disease. Occasionally these clues can be diagnostic, while most are nonspecific reaction patterns. Nail changes occur in the nail plate as a result of nail matrix abnormalities caused by systemic disease and other systemic insults such as reactions to medications. In this article we review some of the more common nail signs that can be used to help diagnose systemic disease.     

Depression in Alzheimer's disease: is there a temporal relationship between the onset of depression and the onset of dementia?

Alzheimer's disease (AD) patients often present with concurrent major depression (MD). To investigate the reasons for this comorbidity, e.g. MD being a risk factor for AD, or both diagnoses having a common neurobiology, the temporal relationship between the first onset of AD and of MD during lifetime was investigated-57 out of 146 AD patients had a lifetime diagnosis of MD. The correlation between the ages at onset of MD and dementia was calculated. The incidence of MD in AD patients in several 5-year-intervals before and after the onset of AD was compared with the average incidence of MD in the present AD sample and with the expected incidence of MD in the general population. No significant correlation between the onset of AD and of MD could be found after controlling for age, gender and the Mini-Mental-State. However, the incidence of MD 5 years before and after the onset of AD significantly exceeded the expected incidences-MD is only partially related to AD. However, the increased incidence of MD within 5 years before and after the onset of dementia may indicate that a common neurobiological process causes cognitive decline and depression in a subsample of AD patients.