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.     

Pr?senile Demenz bei polyzystischer lipomembran?ser Osteodysplasie

Wir berichten über den ersten Fall von polyzystischer lipomembran?ser Osteodysplasie oder “brain, bone and fat disease” in Deutschland. Die nach dem Erstbeschreibern auch als Morbus J?rvi-Hakola-Nasu bezeichnete Erkrankung ist bisher vor allem in Japan und in Finnland beschrieben worden. Einzelne F?lle wurden aus Schweden, Norwegen, Italien, Südafrika, Belgien und den USA berichtet. Im deutschsprachigen Raum ist bisher ein Fall aus ? ver?ffentlicht worden.     

Dependence of blood clot lysis on the mode of transport of urokinase into the clot--a magnetic resonance imaging study in vitro

Magnetic resonance imaging was employed to study the dependence of clot lysing patterns on two different modes of transport of urokinase into whole blood clots. In one group of clots (nonperfused clots, n1 = 10), access of urokinase to the fibrin network was possible by diffusion only, whereas in the other group (perfused clots, n2 = 10) bulk flow of plasma containing urokinase was instituted through occlusive clots by a pressure difference of 3.7 kPa (37 cm H2O) across 3 cm long clots with a diameter of 4 mm. It was determined separately that this pressure difference resulted in a volume flow rate of 5.05 +/- 2.4 x 10(-2) ml/min through occlusive clots. Perfused clots diminished in size significantly in comparison to nonperfused ones already after 20 min (p less than 0.005). Linear regression analysis of two-dimensional clot sizes measured by MRI showed that the rate of lysis was more than 50-times faster in the perfused group in comparison to the nonperfused group. It was concluded that penetration of the thrombolytic agent into clots by perfusion is much more effective than by diffusion. Our results might have some implications for understanding the differences in lysis of arterial and venous thrombi.     

Angiotensin-converting enzyme in sarcoid and chalazion granulomas of the conjunctiva

Angiotensin-converting enzyme (ACE) was studied immunohistochemically in conjunctival biopsies from 6 patients with systemic sarcoidosis, 4 patients with posterior non-sarcoid uveitis and in specimens from 4 patients with chalazion of the eyelid. Specimens with sarcoid granulomas showed intense ACE-positive immunoreactivity in epitheloid cells of the granuloma, whereas chalazion granulomas did not contain ACE-immunoreactivity. There was no difference in staining patterns between specimens without granulomas. Thus immunohistochemical staining for ACE may be of help in differentiating conjunctival granulomatous tissue of a chalazion from sarcoid granuloma.     

Association between human IgM autoantibodies and kappa chain allotypes

The relationship between the immunoglobulin kappa light chain allotypes and autoantibodies was studied in a series of seven human monoclonal kappa-bearing IgM antibodies with Rheumatoid Factor (RF) activity, two IgM anti-low density lipoprotein (LDL) antibodies, and one IgM anti-intermediate filament (IF) antibody. Residues at amino acid positions 153 and 191 related to the Km allotypes in human kappa chains were determined by an HPLC tryptic fingerprint and corroborated by amino acid sequence analysis. All the autoantibodies shared similar variable regions derived from the V kappa IIIb gene(s). The seven RF and the anti-IF were associated with the Km(3) constant region allotype whereas the two anti-LDL were associated with the Km(1,2) allotype. Thus, monoclonal autoantibodies showed the same Km allotypic distribution as the normal population. However, although the number of samples is small, it seems likely that a preferential association may exist between particular V kappa genes and Km alleles in the generation of autoantibodies with different specificities.     

Bioavailability and biological efficacy of a new oral formulation of salmon calcitonin in healthy volunteers.

Salmon calcitonin (SCT) is a well-tolerated peptide drug with a wide therapeutic margin and is administered parenterally for long-term treatments of bone diseases. Its clinical usefulness would be enhanced by the development of an orally active formulation. In this randomized crossover double-blinded phase I trial, controlled by both a placebo and a parenteral verum, we have tested a new oral formulation of SCT associated with a caprylic acid derivative as carrier. Eight healthy volunteers received single doses of 400, 800, and 1200 microg of SCT orally, a placebo, and a 10-microg (50 IU) SCT intravenous infusion. SCT was reliably absorbed from the oral formulation, with an absolute bioavailability of 0.5-1.4%, depending on the dose. It induced a marked, dose-dependent drop in blood and urine C-terminal telopeptide of type I collagen (CTX), a sensitive and specific bone resorption marker, with the effects of 1200 microg exceeding those of 10 microg intravenously. It also decreased blood calcium and phosphate, and increased the circulating levels of parathyroid hormone (PTH) and, transiently, the urinary excretion of calcium. It was well-tolerated, with some subjects presenting mild and transient nausea, abdominal cramps, diarrheic stools, and headaches. This study shows that oral delivery of SCT is feasible with reproducible absorption and systemic biological efficacy. Such an oral formulation could facilitate the use of SCT in the treatment of osteoporosis and other bone diseases.     

Effect of unilateral ureteral occlusion on fibrin deposition in the kidney and renal blood flow during intravascular coagulation in rat

The effect of unilateral ureteral occlusion on fibrin deposition in the kidney and the interrelation of the fibrin deposition and the renal blood flow was studied in rat. Intravascular coagulation in the kidney was induced by infusion of thrombin and inhibition of fibrinolysis with tranexamic acid. The effects unilateral occlusion of the ureter for 1 and 24 h on fibrin deposition and renal blood flow were studied. Fibrin in the kidneys was quantitated by intravenous injection of 125I-labelled fibrinogen 24 h before the experiment. The renal blood flow was measured before and after infusion of thrombin by injection of 85Sr- and 141Ce-labelled microspheres into the left ventricle. After ureteral occlusion for 1 h the deposition of fibrin in the kidneys was unaffected. After 24 h substantially less fibrin deposition was found in the occluded than in the unoccluded kidney (0.3 +/- 0.2 and 5.7 +/- 1.6 mg, respectively; p less than 0.05). Before thrombin infusion the blood flow to the occluded kidney was less than that in the unoccluded kidney (2.1 +/- 0.8 and 3.7 +/- 1.2 ml/min, 100 g body weight, respectively; p less than 0.05). The blood flow after infusion of thrombin was equally reduced in both kidneys. The results contradict the hypothesis that vasoconstriction increases the amount of fibrin in the kidneys in thrombin-induced intravascular coagulation.