Spiral CT angiography and surgical correlations in the evaluation of intracranial aneurysms

We investigated the accuracy of spiral computed tomography angiography (CTA) in the detection and study of intracranial aneurysms by comparing CTA with selective angiograms and surgical findings. Twenty-six patients (9 men and 17 women; mean age 53.1 ± 1.8 years) with suspected intracranial aneurysms were submitted to CTA (1- to 2-mm slices, pitch 1:1, 24 s, RI = 1) after a conventional CT examination showing subarachnoid hemorrhage (SAH) in 19 cases and during neuroradiological investigations performed for other reasons in 7 cases. One hundred twenty to 150 ml iodate contrast agent (0.3–0.4 gI/ml) were injected intravenously at 5 ml/s rate and with 12- to 25-s delay calculated with a preliminary test bolus. Three-dimensional shaded surface display (3D SSD) and maximum intensity projection (MIP) reconstructions were obtained from axial images. Then, within 48 h, all patients were submitted to digital subtraction angiography (DSA), with separate assessment of CTA and DSA findings. Twenty-two aneurysms shown by CTA were confirmed at DSA and surgery (true positives), whereas the vascular lesion was not confirmed at DSA in 2 cases (false positives). The presence of intracranial aneurysms was excluded at both CTA and subsequent DSA in 7 cases (true negatives) and there were no false negatives; sensitivity was 100 %, specificity 77.8 %, and diagnostic accuracy 93.5 %. Computed tomography angiography aneurysm location was confirmed at surgery in all cases, with very high accuracy in assessing the presence of an aneurysm neck (100 %). Computed tomography angiography accurately depicted the aneurysm shape in 20 of 22 cases, but failed to depict its multilobed nature in 2 cases. The mean aneurysm diameter calculated at CTA was 0.99 ± 0.12 cm vs 1.09 ± 0.11 cm at surgery (p < 0.01). The present results suggest that the high sensitivity of CTA, if confirmed by further studies, might help in avoiding having to resort to arteriography after negative CTA in SAH patients. Received 15 July 1997; Revision received 30 September 1997; Accepted 5 November 1997     

Coexpression studies with mutant muscarinic/adrenergic receptors provide evidence for intermolecular "cross-talk" between G-protein-linked receptors.

We have tested the hypothesis that guanine-nucleotide-binding-protein-coupled receptors may be able to interact with each other at a molecular level. To address this question, we have initially created two chimeric receptors, alpha 2/m3 and m3/alpha 2, in which the C-terminal receptor portions (containing transmembrane domains VI and VII) were exchanged between the alpha 2C-adrenergic and the m3 muscarinic receptor. Transfection of COS-7 cells with either of the two chimeric constructs alone did not result in any detectable binding activity for the muscarinic ligand N-[3H]methylscopolamine or the adrenergic ligand [3H]rauwolscine. However, cotransfection with alpha 2/m3 and m3/alpha 2 resulted in the appearance of specific binding sites (30-35 fmol/mg of membrane protein) for both radioligands. These sites displayed ligand binding properties similar to those of the two wild-type receptors. Furthermore, COS-7 cells cotransfected with alpha 2/m3 and m3/alpha 2 were able to mediate a pronounced stimulation of phosphatidylinositol hydrolysis upon stimulation with the muscarinic agonist carbachol (Emax approximately 40-50% of wild-type m3). A mutant m3 receptor (containing 16 amino acids of m2 receptor sequence at the N terminus of the third cytoplasmic loop) that was capable of binding muscarinic ligands but was virtually unable to stimulate phosphatidylinositol hydrolysis was also used in various cotransfection experiments. Coexpression of this chimeric receptor with other functionally impaired mutant muscarinic receptors (e.g., with an m3 receptor containing a Pro-->Ala point mutation in transmembrane region VII) resulted in a considerable stimulation of phosphatidylinositol breakdown after carbachol treatment (Emax approximately 40-50% of wild-type m3). Thus, these data suggest that guanine-nucleotide-binding-protein-coupled receptors can interact with each other at a molecular level. One may speculate that the formation of receptor dimers involving the intermolecular exchange of N- and C-terminal receptor domains (containing transmembrane domains I-V and VI and VII, respectively) may underlie this phenomenon.     

Longitudinal Changes in BMD and Bone Geometry in a Population‐Based Study

We prospectively examined vBMD and structural bone parameters assessed by QCT among participants of the InCHIANTI study over a 6‐yr follow‐up. Periosteal apposition occurred both in men and women. Endocortical resorption causes bone loss in older women despite periosteal apposition. Introduction: To address the hypothesis that age‐related changes in BMD and bone geometry may be different in men and women, we prospectively examined volumetric BMD (vBMD) and structural bone parameters assessed by QCT among participants of the InCHIANTI study over a 6‐yr follow‐up. Materials and Methods: Three hundred forty‐five men and 464 women 21–102 yr of age from the InCHIANTI study, a population‐based study in Tuscany, Italy, were included. Tibial QCT bone parameters were measured at enrollment (1998–2000) and at 3‐ (2001–2003) and 6‐yr (2004–2006) follow‐ups. Results: Periosteal apposition occurred both in men and women. The annual rate of bone periosteal apposition was higher in younger than in older men, whereas in women, the rate of apposition was homogenous across age groups. The age‐related medullary expansion, expression of endocortical resorption, was significantly higher in women compared with men. In women, but not in men, accelerated endocortical resorption not sufficiently balanced by periosteal apposition caused accelerated loss in cortical bone mass. The cross‐sectional moment of inertia decreased progressively over the life span in both sexes. Conclusions: Endocortical resorption causes bone loss in older women despite periosteal apposition. Obtaining a balance between endocortical resorption and periosteal apposition should be the target for interventions aimed to decrease bone loss and prevent osteoporosis in older women.     

Substance P receptors on canine chief cells: localization, characterization, and function

Saturable binding sites for 125I-Bolton-Hunter substance P were observed in frozen sections of the oxyntic mucosa of the canine stomach using quantitative autoradiography. The cell type possessing substance P binding sites in this region was identified as the chief cell in 2 ways. First, the saturable binding of radioiodinated substance P correlated with chief cell content (and not with parietal cell content, for example) in dispersed oxyntic mucosal cells fractionated by centrifugal elutriation. Second, saturable binding of radioiodinated substance P was localized to dispersed chief cells by autoradiography using emulsion-coated preparations of isolated cells affixed to glass slides. Parietal and mucous cells did not bind substance P. In studies of enriched chief cell preparations, the binding of radiolabeled substance P was found to be time- and cell number-dependent, specific, saturable, reversible, and of high affinity. Equilibrium binding analysis revealed a single class of binding sites with an apparent Kd of 105 pM and a Bmax of 3000 receptors per cell. In competitive displacement studies, the order of potency of analogs for inhibition of the saturable binding of radiolabeled substance P to chief cells was substance P = physalaemin greater than substance K greater than neuromedin K; thus, the chief cell has a substance P-preferring tachykinin binding site. Bombesin, cholecystokinin, and somatostatin had no effect on substance P binding. Substance P stimulated pepsinogen secretion from isolated canine oxyntic glands in dose-dependent fashion with a half-maximal response occurring at a substance P dose of about 1 mM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmakologische Studien über Thiazole

Zusammenfassung An Ratten wurde die Wirkung der 2-Amino-5-methylthiazol-4-carbonsäure bei Äthylalkoholvergiftung untersucht. Sie übt — analog dem Vitamin B₁ — eine schützende Wirkung sowohl hinsichtlich des klinischen Bildes, wie der anatomischen und histologischen Veränderungen gegenüber der Alkoholvergiftung aus.Mit 4 Textabbildungen.     

Rapid and simultaneous typing of hemoglobin S, hemoglobin C, and seven Mediterranean beta-thalassemia mutations by covalent reverse dot-blot analysis: application to prenatal diagnosis in Sicily

The molecular lesions causing beta-thalassemia in Sicily can be subdivided into two groups. One that occurs at a 71% frequency and consists of the beta 39, IVS 1,110 and IVS 1,6 mutations and the other group at a 20% frequency comprising the -87, beta s, IVS 1,1 and IVS 2,745 mutations. The identification of all these mutations by polymerase chain reaction (PCR) and conventional dot-blot hybridization has been time consuming and expensive. In this article, we describe the implementation of the reverse dot-blot (RDB) hybridization as a rapid nonradioactive method for the identification of the nine most frequent molecular lesions in the beta-globin gene (-87, beta s, beta c, IVS 1,1, IVS 1,6, IVS 1,110, beta 39, IVS 2,1, IVS 2,745) in Sicily. Sixty prenatal diagnoses were performed by this RDB assay, each of which was confirmed by dot-blot/ASO hybridization; thus demonstrating the accuracy of the RDB. The main advantage of this assay is the rapid typing of an individual's DNA for many mutations in a single working day. Because the mutations in this assay are representative for the Mediterranean region, this mutational panel can also be extended to the screening of beta-thalassemia from other Mediterranean regions.     

Autoradiographic localization and characterization of tachykinin receptor binding sites in the rat brain and peripheral tissues

Quantitative receptor autoradiography using several radiolabeled tachykinins was used to localize and characterize tachykinin peptide receptor binding sites in rat CNS and peripheral tissues. Autoradiographic localization and displacement experiments using several radiolabeled tachykinins indicate that in the rat there are at least 3 distinct tachykinin receptor binding sites. One of these is present in both the CNS and peripheral tissues, one is present only in the CNS, and one is present only in peripheral tissues. The first tachykinin receptor binding site, which is detectable in both the CNS and peripheral tissues, appears to prefer substance P (SP) as an endogenous ligand. Areas expressing high concentrations of this binding site include the medial septum, superior colliculus, inferior olive, inner plexiform layer of the retina, external muscle of the bladder, and the muscularis externa of the esophagus. The second type of tachykinin receptor binding site, which is detectable only in the CNS appears to prefer either neuromedin K (NK) and/or substance K (SK) as the endogenous ligand. This receptor binding site is labeled by Bolton-Hunter conjugates of NK, SK, eledoisin, or kassinin and is found in high concentrations in laminae 4 and 5 of the cerebral cortex, the ventral tegmental area, laminae 1 and 2 of the spinal cord, and the inner plexiform layer of the retina. The third type of tachykinin receptor binding site is detectable only in peripheral tissues and appears to prefer SK as the endogenous ligand. This receptor binding site is labeled by SK, eledoisin, or kassinin radioligands and tissues that express high concentrations include the muscularis mucosae of the esophagus, the circular muscle of the colon, and the external muscle of the bladder. These data suggest that SP receptors are expressed in the brain and peripheral tissues, NK receptors are expressed in the CNS, and SK receptors are expressed in peripheral tissue. These data fit well with radioimmunoassay data that suggest that, whereas in the CNS SP, SK and NK are present in high concentrations, in peripheral tissues only SP and SK are present in detectable concentrations. The present classification of tachykinin receptors places a lower limit on the number of mammalian tachykinin receptor types and provides a functional/morphological framework for exploring the diverse actions of tachykinin peptides in both the CNS and peripheral tissues.     

Antigen-dependent alterations in the lipid composition of the CNS in guinea pigs with experimental allergic encephalomyelitis

Stimulation of LH release following electrochemical stimulation (EC) of median eminence-arcuate region (ME-ARC) during various stages of 5-day estrous cycle of rat has been studied. On day 2 post-ovulation (diestrus II), when the vaginal smear consisted of leucocytes, elevations in plasma LH as a result of ME-ARC stimulation were minimal. With the change in vaginal smear to nucleated epithelial cells on day 3 (proestrus I) and cornified cells on day 4 (proestrus II) post-ovulation EC stimulation induced significantly higher elevations in plasma LH than those obtained following stimulation on diestrus II. To determine whether neural links between medial preoptic area and ME-ARC are essential during the period in which the marked changes in sensitivity of ME-ARC to EC stimulation occur, the anterior hypothalamus was partially deafferented (AAD) in rats at various stages of the estrous cycle.Plasma LH levels following EC stimulation of ME-ARC at 18.00 h of proestrus I were assessed in these AHD rats. LH levels were found to be correlated with cell types present in the vaginal smear at the time of EC stimulation. Nucleated epithelial cells were present at the time of stimulation in rats deafferented at 09.00 h of proestrus I or 18.00 h of diestrus II and in 5/9 rats at 08.00 h of diestrus II similar to the control rats in which sham AHD was performed at 09.00 h of fiestrus II or of proestrus I. Elevations in plasma LH after stimulation in these rats were comparable to those observed in sham AHD control rats. Quite different results were obtained when AHD was performed at 17.00 h of diestrus I or at 08.00 h of fiestrus II (4/9 rats). Vaginal smear consisted of leucocytes; and slight elevations of plasma LH after stimulation of ME-ARC were detected. However, administration of estradiol benzoate (5 μg/rat) 12 h after AHD at diestrus I not only induced cornification of vagina but also restored the plasma LH values to those obtained following stimulation of ME-ARC of intact or sham AHD control rats. These results indicate that maximal LH release following ME-ARC stimulation of deafferented rats requires estrogen priming.