Clinical assessment of patients with Graves' orbitopathy: the European Group on Graves' Orbitopathy recommendations to generalists, specialists and clinical researchers.
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Endocrinology↗
Biomedical subjects
A Boschi
Publications and source records attributed to A Boschi.
Quantification of cells expressing the thyrotropin receptor in extraocular muscles in thyroid associated orbitopathy.
BACKGROUND/AIM: Thyroid associated orbitopathy (TAO) and Graves' disease (GD) have an autoimmune pathogenesis, possibly related to the thyrotropin receptor (TSHR). The aim of this study was to determine whether TSHR immunoreactivity is correlated with disease severity or serum TSHR antibody (TRAB) levels. METHODS: Orbital tissues from 30 patients with TAO were compared with those of 20 patients with strabismus and four with non-thyroid orbital inflammation. TSHR was detected by immunohistochemistry and TRAB were measured by radioreceptor assay. RESULTS: No TSHR immunoreactivity was detected in the 24 control orbital tissues, whereas in all TAO biopsies elongated fibroblast-like cells, expressing TSHR, were present. These cells were located between the muscle cells, which were separated by oedema in the acute phase but fibrous tissue in the chronic phase of disease. Semi-thin sections showed numerous mast cells present in the chronic phase and in close contact with adipocytes. The number of TSHR immunostained cells was high in early disease, decreased with disease duration, and was positively correlated with TRAB levels at the onset of TAO. CONCLUSION: TSHR immunoreactivity was demonstrated specifically in TAO orbits which highlights the importance of TRAB early in the pathogenesis.
Adult↗
Visual prognosis after indirect traumatic optic neuropathy.
OBJECTIVE: To investigate a possible correlation between final visual acuity and the presence at baseline of various systemic and local (orbital/ocular) signs in patients affected by indirect traumatic optic neuropathy. METHODS: 35 cases of traumatic optic neuropathy were examined retrospectively and 13 variables were tested. Univariate analysis with "no recovery of visual acuity" as the primary outcome was performed. Relative risk (RR) and 95% confidence intervals (CI) were calculated. Fisher's exact test was used for two variables to test differences between proportions. RESULTS: Four variables showed a significantly increased risk for no recovery of visual acuity: presence of blood within the posterior ethmoidal cells (RR = 2.25, 95% CI 1.25 to 4.04); age over 40 years (RR = 1.79, 1.07 to 2.99); loss of consciousness associated with traumatic optic neuropathy (RR = 2.21, 1.17 to 4.16); and absence of recovery after 48 hours of steroid treatment (p < 0.01, Fisher's exact test). Recovery documented at the first follow up visit after treatment was significantly associated with recovery at the last follow up visit (p < 0.01, Fisher's exact test). CONCLUSIONS: These four negative prognostic signs in patients affected by traumatic optic neuropathy may be useful in predicting the visual outcome in patients developing visual loss after head trauma and in deciding on the need for surgical treatment.
Adult↗
A class of asymmetrical nitrido 99mTc heterocomplexes as heart imaging agents with improved biological properties.
Asymmetrical heterocomplexes containing a terminal technetium-nitrogen multiple bond coordinated to one diphosphine ligand (PNP) and one dithiocarbamate ligand (DBODC), were obtained through a simple two-step procedure under controlled conditions. The resulting complexes [99mTc(N)(PNP)(DBODC)]+ are monocationic, and possess a distorted square-pyramidal geometry where the Tc triple bond N multiple bond occupies an apical position and the diphosphine and dithiocarbamate ligands span the residual four coordination positions on the basal plane through the two phosphorus atoms and the two sulfur atoms, respectively. Biodistribution data in rats demonstrated that these complexes were rapidly extracted by the myocardium, and retained in this region for a prolonged time. After a few minutes post-injection, lung uptake became negligible, and liver washout was extremely rapid and quantitative. Analysis of heart/liver uptake ratios for these complexes revealed that their values increased exponentially in time, and after 60 min post-injection liver activity was almost completely eliminated into the intestine. Comparison with heart/liver ratios determined for 99mTc sestamibi and 99mTc tetrfosmin showed that values for these latter compounds were approximately 10 times lower than those measured for [99mTc(N)(PNP)(DBODC)]+ complexes at 60 min post-injection. In conclusion, the monocationic tracers [99mTc(N)(PNP)(DBODC)]+ exhibit high myocardial uptake in rats and dramatically high heart/lung and heart/liver ratios, suggesting that this novel class of perfusion agents could be conveniently employed to obtain heart images with superior imaging quality.
Animals↗
Involvement of the Mycobacterium tuberculosis secreted antigen SA-5K in intracellular survival of recombinant Mycobacterium smegmatis.
A new protein (SA-5K) secreted in culture filtrates by Mycobacterium bovis, Mycobacterium tuberculosis, and few other mycobacterial species was previously identified and purified in our laboratory. In order to evaluate the putative role of SA-5K during intracellular mycobacterial growth, in the present study the SA-5K gene was cloned and expressed in Mycobacterium smegmatis, a rapid growing non-pathogenic mycobacterium which does not contain the gene for the protein. SA-5K expression in the THP-1 human macrophage cell line infected with the recombinant strain (M. smegmatis-pROL5K) was demonstrated by RT-PCR on RNA extracted from bacterial cells following 24 and 48 h of infection. Intracellular SA5K expression was associated with a higher cfu increase of M. smegmatis-pROL5K in comparison to the negative control strain (M. smegmatis recombinant for the cloning vector) (P=0.01). No significant change in SA-5K synthesis by M. smegmatis-pROL5K was observed when the recombinant strain was grown in vitro in different stress conditions such as iron deprivation, pH 4.5, presence of nitric oxide or hydrogen peroxide. The results presented in this study suggest a possible role for SA-5K in intracellular survival of recombinant M. smegmatis, though the function of the protein remains unknown.
Antigens, Bacterial↗
Use of a recombinant strain of Mycobacterium avium expressing beta-galactosidase to evaluate the activities of antimycobacterial agents inside macrophages.
A reliable and low-cost method that enables rapid screening of the activity exerted by new antimicrobial agents on intracellularly growing Mycobacterium avium has been developed. To this aim, a recombinant (lacZ) strain of M. avium expressing the Escherichia coli beta-galactosidase gene was used to evaluate, in murine macrophages, the susceptibility of M. avium to common antimycobacterial agents. beta-Galactosidase levels, measured in the presence of each of the antibiotics tested, were closely correlated with the number of CFU recovered from the M. avium lacZ strain-infected macrophages.
Animals↗
[Susac syndrome in a man].
The association of an acute encephalopathy, neurosensory hearing loss and retinal branch artery occlusions in a 35 year old man as well as the absence of systemic disease suggest the diagnosis of Susac's syndrome. This is the eighth male case described, the syndrome being more frequently reported in females.
Adult↗
Substituent dependence of the diastereofacial selectivity in iodination and bromination of glycals and related cyclic enol ethers.
The stereochemical course of the electrophilic iodination and bromination of tri-O-benzyl-D-glucal under various conditions has been compared to that of substituted dihydropyrans 2-5. IN(3) addition in acetonitrile affords trans-alpha-iodoazides (80-87%), besides small amounts of trans-beta-adducts, in the presence or the absence of benzyloxy substituents at C-3 or C-4, and in agreement with bridged iodonium ion intermediates. In contrast, the diastereofacial selectivity of bromine addition in dichloroethane going through open bromo oxocarbenium ions depends strongly on the substituents. Whereas the trans-alpha-dibromides are the main (85-95%) adducts in the absence of C-4 and C-5 substituents, in their presence a moderate to exclusive selectivity for cis-alpha-addition (60-99%) is observed. The predominance of trans-alpha-addition is again observed whatever the substituents when the bromination is carried out in the same solvent but with a tribromide ion salt, supporting a concerted addition of the two bromine atoms under these conditions. Finally, bromine addition in methanol exhibits a completely different behavior with the nonselective formation of trans-alpha- and trans-beta-methoxybromides and a small dependence on the substituents. In agreement with the absence of azide trapping of any cationic intermediate, it is concluded that these brominations which do not go through an ionic intermediate are concerted additions of bromine and methanol with very loose rate- and product-determining transition states. Finally, the substituent conformation at C-4 influences drastically the stereoselectivity in all these brominations. Evidence for alpha-anomeric control of the nucleophile approach at C-1 is given by the highly predominant formation of alpha-adducts, except in the methanolic bromination. The factors determining the versatile selectivity of the electrophile approach are discussed in terms of PPFMO theory and of the special mechanisms of glycal reactions.
Journal Article↗
An alternative approach to the preparation of (188)Re radiopharmaceuticals from generator-produced [(188)ReO(4)](-): efficient synthesis of (188)Re(V)-meso-2,3-dimercaptosuccinic acid.
A new efficient approach for the preparation of (188)Re radiopharmaceuticals starting from [(188)ReO(4)](-), produced at a carrier-free level through the (188)W/(188)Re generator system, is described. The reaction procedure was based on the combined action of different reagents and has been applied in detail to the preparation of the therapeutic agent (188)Re(V)-DMSA (H(2)DMSA [meso-2,3-dimercaptosuccinic acid]). The most efficient combination required the use of SnCl(2), oxalate ions, and gamma-cyclodextrin. These were reacted with [(188)ReO(4)](-) and H(2)DMSA to afford the final radiopharmaceutical in high radiochemical purity, at room temperature, and in weakly acidic solution. The role played by the various reagents in the reaction was investigated. It was found that SnCl(2) behaved as the actual reducing agent, whereas oxalate and gamma-cyclodextrin greatly enhanced the ease of reduction of [(188)ReO(4)](-) through the action of two hypothetical mechanisms. In the first step of the reaction, oxalate ions gave rise to the formation of Re(VII) complexes with the concomitant expansion of the coordination sphere of the metal. This process strongly favored the electron transfer between Sn(2+) and Re(+7) centers, giving rise to intermediate reduced rhenium complexes. These species were further stabilized by the formation of transient host-guest aggregates with gamma-cyclodextrin and finally converted into (188)Re(V)-DMSA through simple replacement of the coordinated ligands by H(2)DMSA.
Cyclodextrins↗
Synthesis of a novel class of nitrido Tc-99m radiopharmaceuticals with phosphino-thiol ligands showing transient heart uptake.
A novel class of technetium-99m radiopharmaceuticals showing high heart uptake is described. These complexes were prepared through a simple and efficient procedure, and their molecular structure fully characterized. They are formed by a terminal Tc(triple bond)N multiple bond and two bidentate phosphine-thiol ligands [R(2)P-(CH(2))(n)SH, n=2,3] coordinated to the metal ion through the neutral phosphorus atom and the deprotonated thiol sulfur atom. The resulting geometry was trigonal bipyramidal. Biodistribution studies were carried out in rats. The complexes exhibited high initial heart uptake and elimination through liver and kidneys. The washout kinetic from heart was dependent on the nature of the lateral R groups on the phosphine-thiol ligands. When R=phenyl, heart activity was rapidly eliminated within 10-20 min. Instead, when R=tolyl, cyclohexyl, persistent heart uptake was observed. Extraction of activity from myocardium tissue showed that no change of the chemical identity of the tracer occurred after heart uptake. On the contrary, metabolization to more hydrophilic species occurred in liver and kidneys.
Animals↗
A CD(4)/T(4) receptor peptide ligand labeled with technetium-99m: synthesis and biological activity.
The octapeptide D-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-NH(2) ([D-Ala(1)]TNH(2)), an analog of peptide T (H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH) associated with CD(4)/T(4) receptors involved in human immunodeficiency virus infection, was combined with the chelating polyazamacrocycle 1,4,8,11-tetraazacyclotetradecane (cyclam) to afford the bifunctional ligand cyc-[D-Ala(1)]TNH(2). This was then reacted with [(99m)TcO(4)](-) and Sn(2+) to yield the monocationic complex [(99m)Tc(O)(2)(cyc-[D-Ala(1)]TNH(2))](+). Biological activity of both the cyclam-peptide conjugate and the resulting Tc-99m complex were evaluated by measuring their chemotactic indexes. Results showed that N-cyclam acylation and subsequent labeling with Tc-99m of [D-Ala(1)]TNH(2) were tolerated, and both cyc-[D-Ala(1)]TNH(2) and [(99m)Tc(O)(2)(cyc-[D-Ala(1)]TNH(2))](+) retained the high chemotactic capacity of the original octapeptide. Biodistribution of the Tc-99m complex was carried out in rats. Fast blood clearance and no accumulation in organs of interest were observed.
Animals↗
Optic nerve sheath meningiomas: clinical features, functional prognosis and controversial treatment.
Optic nerve sheath meningiomas (ONSM) are rare benign neoplastic lesions arising from meningothelial cells of the meninges. As clinical features are highly variable, the diagnosis is often delayed. From 1995 to 1999, 6 patients were diagnosed with ONSM in our department. We compared our series with the literature data. Visual prognosis is usually poor. Despite a large literature, the treatment guidelines are still highly controversial.
Adult↗
Design and synthesis of a redox-active Tc-99m radiopharmaceutical with ferrocenedithiocarboxylate [FcCS = Fe(C5H4CS2)(C5H5)-].
The synthesis, at tracer level, of two Tc-99m complexes having the same chemical composition and structure, but differing by one electron in the total electron counting, is reported. These compounds have been prepared by reacting [99mTcO4]- with the piperidinium salt of the ligand ferrocenedithiocarboxylate {[Fe(II)(C5H4CS2)(C5H5)]- = FcCS}, in the presence of N-methyl S-methyldithiocarbazate as donor of N3-groups, and triphenylphosphine or SnCl2 as reducing agents. The formation of the neutral complex [99mTc(N)(FcCS)2] (compound A) and of the monocationic, mixed-valence complex [99mTc(N)(FcCS) (FcCS)]+ (compound B) {FcCS = [Fe(III)(C5H4CS2)(C5H5)]} was obtained in high yield. Both complexes comprise a terminal Tc triple bond N multiple bond and two FcCS ligands coordinated to the metal center through the two sulfur atoms of the -CS2 group, but they differ in the oxidation state of one of the two iron atoms of the coordinated FcCS ligands. In complex A, the two Fe atoms are both in the +2 oxidation state, while in B, one Fe atom is in the +2 and the other is in the +3 oxidation state. Thus, B is a mixed-valence Fe(II)-Fe(III) complex. B is easily converted into A by one-electron exchange with various reductants such as triphenylphosphine and excess SnCl2. Biodistribution studies in rats showed that complexes A and B are mostly retained in lungs and liver without any significant uptake in organs such as heart and brain.
Animals↗
Evoked potentials investigation of visual dysfunction after methanol poisoning.
OBJECTIVE: To present results of electrophysiologic investigations of the visual toxicity observed during the early stage of methanol poisoning. DESIGN: Retrospective, clinical study. SETTING: A 7-bed intensive care unit in a university hospital. PATIENTS: Nineteen patients admitted with a diagnosis of acute methanol poisoning. INTERVENTIONS: Visual evoked potentials were obtained within the first 48 hrs after admission; a clinical follow-up examination was performed in 11 patients, and 12 patients were followed up by visual evoked potentials beyond the same delay. Correlations between the occurrence of an optic neuropathy and clinical, biological, and electrophysiological data were studied. MEASUREMENTS AND MAIN RESULTS: A significant correlation was found between arterial pH and blood formate concentration (r2 = 0.58, p = .003), between blood formate and bicarbonate concentrations (r2 = 0.36, p = .02), and between delay from ingestion and blood formate concentration (r2 = 0.44, p = .017). Clinical outcome was correlated not only with the bicarbonate (p = .007), formate (p = .018), and methanol (p = .03) concentrations and arterial pH (p = .004) but also with a well-defined electrophysiologic pattern during the acute stage. An index of global cortical functioning > or =3 was associated with death, whereas a global cortical functioning index < or =2 was associated with survival (p = .0058). Moreover, a statistically significant difference in long-term visual impairment was found between the subgroup with abnormal wave III morphology or a global cortical functioning index of 1-2 and the subgroup with normal wave III morphology and a global cortical functioning index <1 (p = .015). Results of the electrophysiologic studies were expressed as retinal dysfunction and optic nerve injury. Five patients had normal findings on electrophysiologic examination. Ten patients had early signs of retinal dysfunction that were fully reversed in the eight patients who were followed. Ten patients had persistent electrophysiologic signs of optic neuropathy. CONCLUSIONS: Although reversible retinal dysfunction is evident in the early stage of human methanol poisoning, its absence does not preclude development of optic neuropathy. The occurrence of optic neuropathy and early electrophysiologic data are correlated.
Acute Disease↗
Neuroophthalmologic manifestations of systemic disease.
Significant contributions on the neuroophthalmologic manifestations of systemic disease have been published in the past year. The first part of this paper is devoted to practical guidelines that may help in the diagnosis and the management of oculomotor disorders, especially in connection with systemic diseases; the second part is focused on specific entities. Including idiopathic intracranial hypertension and ophthalmoplegic migraine in this review might be debatable; however, although the cause of these conditions is still unclear, relevant findings suggest that they may be the consequence of other adjacent processes rather than the cause itself. We believe that the diagnosis of idiopathic intracranial hypertension as well as that of ophthalmoplegic migraine remains a challenging issue for the ophthalmologist and may easily be overlooked.
Acquired Immunodeficiency Syndrome↗
[Craniopharyngioma: ophthalmological manifestations and prognosis after treatment].
The craniopharyngioma is a benign tumor located at least in part in the suprasellar cistern. The symptoms are determined not only by the position of the tumor but also by its size and the age of the patient. The goal of our study is to analyse retrospectively the manifestations of craniopharyngioma and their prognosis after treatment in function of the age.
Adolescent↗
The uvp1 gene on the R46 plasmid encodes a resolvase that catalyzes site-specific resolution involving the 5'-conserved segment of the adjacent integron In1.
The product of the uvp1 gene of the R46 plasmid, a member of the DNA invertase-resolvase family, was studied to characterize its recombination activity on the R46 plasmid. The purified Uvp1 protein specifically binds to a 256-bp DNA fragment located immediately upstream of the uvp1 gene itself, and overlapping the 5'-conserved segment (5'-CS) of the R46 integron In1. We identified on this fragment a putative resolution (res) site. Using an in vitro assay, we demonstrated the ability of the protein to resolve a synthetic cointegrate containing a direct repeat of the res site. In vivo, we obtained cointegrate resolution in Uvp1-expressing recA- cells. Sites I and II, subsites of the putative res site, lie within the outer boundary of the integron 5'-CS which is common to all the known integrons. Furthermore, a 69-bp DNA element (containing site I) is required for cointegrate resolution. We propose that this recombination mechanism protects R46 plasmid against unequal distribution following fusion with either identical or different integron-bearing plasmids. Moreover, Uvp1 might have a role in generating gene cassette diversity between the two conserved segments of the integron.
Bacterial Proteins↗
Malignant bilateral exophthalmos and secondary glaucoma in iatrogenic Cushing's syndrome.
The authors describe a case of iatrogenic Cushing's syndrome in which an emergency orbital decompression was performed. This procedure was necessary because major ocular hypertension and severe bilateral exophthalmos had caused a decrease in visual function and recurrent painful episodes of eyeball luxation.
Chronic Disease↗