Results of 3-stage treatment: (I) corticotherapy, (II) linear acceleration and (III) orbital decompression in 206 patients with malignant Graves ophthalmopathy]

There is no, so far, a rational method of therapy based upon the etiology of autoimmune Graves' ophthalmopathy. As a malignant Graves' ophthalmopathy we defined the most severe eye changes leading to the sight loss or permanent disability of vision which are classified as exceeded class 3c according to the eye changes classification of the American Thyroid Association [27]. The aim of the study was to develop the most efficacious method of therapy for malignant Graves' ophthalmopathy. The material consisted of 206 patients treated according to the 3-stage method: 1-st--corticotherapy, 2-nd--radiotherapy, including linear accelerator, 3-rd--orbital decompression. Moreover, in four patients plasmapheresis was applied and in additional five cyclosporine was administered. In all 206 patients the estimation of the results of the treatment was based on the Donaldson ophthalmopathy index [4]. It has been proved that corticotherapy combined with linear accelerator radiotherapy has been the most efficacious method of treatment. It has also the least number of side effects. Orbital decompression as the 3-rd stage of treatment was employed in those cases in which the previous two stages of medical therapy were unsuccessful.     

Detection of the novel autoantibody (anti-UACA antibody) in patients with Graves' disease

Uveal autoantigen with coiled coil domains and ankyrin repeats (UACA) is an autoantigen in patients with panuveitis such as Vogt-Koyanagi-Harada disease. The prevalence of IgG anti-UACA antibodies in patients with uveitis is significantly higher than healthy controls, suggesting its potential role as an autoantigen. Originally, UACA was cloned from dog thyroid tissue following TSH stimulation. So, we presumed UACA could be a novel autoantigen in autoimmune thyroid diseases. We measured serum anti-UACA antibody titer using ELISA in patients with autoimmune thyroid diseases (Graves' disease, Hashimoto's thyroiditis, subacute thyroiditis, and silent thyroiditis). The prevalence of anti-UACA antibodies in Graves' disease group was significantly higher than that in healthy group (15% vs. 0%). Moreover, the prevalence of anti-UACA antibodies in Graves' ophthalmopathy was significantly higher than that in Graves' patients without ophthalmopathy (29% vs. 11%). Especially, 75% of severe ocular myopathy cases showed high UACA titer. Immunohistochemical analysis revealed that UACA protein is expressed in eye muscles as well as human thyroid follicular cells. Taken together, UACA is a novel candidate for eye muscle autoantigens in thyroid-associated ophthalmopathy.     

Disturbance of larval orientation in Spodoptera frugiperda (Lepidoptera : Noctuidae) by microsurgical removal of endocrine centres

The larvae of S. frugiperda showed differences in orientation depending largely upon their physiological states. A preference for wet conditions manifested itself in the orientation of the penultimate instar larvae, whereas the larvae of the final stage exhibited preference neither for wet nor for dry conditions. However, the ‘light level’ proved to be of prime importance in the final stage, such that it drove the larvae almost exclusively to the dark, while it appeared to be of secondary importance in the preceding stage where the larvae only responded photopositively if deprived of the humidity-preference.Microsurgical removal of the medial neurosecretory cells in the pars intercerebralis resulted in a preference for dry conditions in both larval instars concomitant with an appreciable increase in the total water content of the larvae. The normal situation could be easily restored by implantation of some active cells. Allatectomy failed to alter the normal preferences of the final instar larvae, whereas it induced a humidity-preference in the larvae of the penultimate stage, a response exhibited normally by intact larvae of the final stage. This result might suggest the implication of the morphogenetic hormones in some way or another in the control of larval response to the ‘humidity level’. However, photopreference in both larval instars appeared to be genetically controlled.     

PALEO-PGEM-Series: A spatial time series of the global climate over the last 5 million years (Plio-Pleistocene)

Motivation

Climate change plays an important role in the generation and maintenance of biodiversity by driving processes such as diversification and range shifts. As a result, biodiversity patterns are often found to carry the imprints of palaeoclimatic changes. However, we still know little about the spatial and temporal variation in climate over the scale of millennia affecting eco-evolutionary dynamics, mostly because of the scarcity of user-friendly and freely available spatio-temporal palaeoclimate series at such temporal scales. Here, we address this gap by presenting PALEO-PGEM-Series, a global spatio-temporal dataset of the last 5 Myr, with 1 kyr resolution, spatially downscaled from emulations performed with the intermediate-complexity atmosphere–ocean general circulation model PALEO-PGEM. PALEO-PGEM-Series holds the potential to advance our understanding of the mechanisms behind the strong relationship between biodiversity and climate, a pressing need given projected biodiversity responses to anthropogenic climatic change.

Main Types of Variables Contained

Spatio-temporal series of monthly temperature and precipitation and 17 derived bioclimatic variables over the Pliocene–Pleistocene, along with standard error estimates from multiple runs of the emulator.

Spatial Location and Grain

Global landmasses, at 1° × 1°.

Time Period and Grain

Last 5 Myr at 1000 year resolution.

Major Taxa and Level of Measurement

Not applicable.

Software Format

Tab-delimited text files and accompanying R code to derive bioclimatic variables.     

Utilization of extremely low frequency (ELF) magnetic fields in chronic disease; five years experience: three case reports

We present three examples of the use of ELF magnetic therapy, two cases of multiple sclerosis and one of chronic pulmonary disease. In each of the two MS cases the Seqex device was applied as an adjunct to antioxidant medication two times a week for six weeks. Radiological and MRI examination indicated improvement in the two MS patients and stabilization in the patient with obstructive pulmonary disease following merely five treatments.     

Epidemiology of onychomycosis and paronychia in the area of ANCONA (ITALY) over a period of 5 years

We retrospectively evaluated the epidemiology of onychomycosis and/or paronychia in 172 patients attending the Clinic of Dermatology and Venereology over a 5 year period. Although yeast isolates, belonging to the Candida species, represented the most frequent etiologic agents of these infections, an increasing prevalence of fungal infections due to emerging fungal pathogens (EFP) was noted throughout this time period. In particular, EFP as causative agents of these infections increased from 0 to 28.4% from 1998 to 2002.     

The French aerobiological monitoring network: two years of clinical experience (1986–1987)

Summary Two years of clinical experience on allergic patients strictly related to tree and grass pollen counts have been reported. In order to carry out investigations, the Institut Pasteur in Paris utilized a questionnaire on which symptoms and drug scores have been daily reported. Together with the pollen concentration, temperature variations and rainfalls have been checked. These investigations pointed out a great variability of the factors taken into account; thus, the way of forecasting allergic symptons seems difficult to find.     

Stimulation of human fat cell adenylate cyclase by GDP and guanosine 5'-O-(2-thiodiphosphate)

GDP regulation of basal and receptor-mediated catecholamine-sensitive human fat cell adenylate cyclase was studied using purified plasma membrane preparations and assay conditions selected to minimize conversion of GDP to GTP. Under ordinary assay conditions (low NaCl concentration) and with App(NH)p as substrate to prevent GDP conversion to GTP, basal enzyme activity was stimulated up to 2-fold by GDP (0.1 mM) while addition of epinephrine (0.1 mM) eliminated stimulation by GDP and reduced basal adenylate cyclase activity. With ATP as substrate, the enzyme was not responsive to hormone in the absence of guanyl nucleotides and GDP augmentation of basal activity was small (0-1.5-fold) while stimulatory effects of epinephrine and isoproterenol were minimally but definitely exhibited (1.5-fold over basal). Guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), a GDP analog resistant to phosphorylation and hydrolysis and an antagonist of GTP, stimulated enzyme activity more than did GDP but did not promote epinephrine action. Rather, inhibition of GDP beta S-stimulated adenylate cyclase activity was seen with both epinephrine and isoproterenol and also with GTP. In the presence of NaCl (200 mM), which alone produced 2-3-fold increase in basal enzyme activity, GDP (0.1 mM) and GDP beta S (50 microM) produced 8- and 15-fold increases of activity, respectively. Addition of UDP, to prevent possible conversion of GDP to GTP, had no effect on NaCl-enhanced activation by GDP. The results indicate that the human fat cell adenylate cyclase system is unique in responding to GDP and its analog GDP beta S by stimulation in the absence of hormone but suggest that as in other systems catecholamine-mediated stimulation is normally dependent on GTP. Salts (Na+) appear to stimulate the enzyme by facilitating the interaction of the guanyl nucleotide regulatory protein (N8) with the catalytic unit.     

Detection of tsh binding inhibiting antibodies (TBI-ab) and thyroid adenylate cyclase stimulating antibodies (TS-ab) in sera of patients with Graves' disease

In the sera of patients with Graves' disease have been demonstrated the immunoglobulins able to inhibit the binding of TSH to the human thyroid membrane (TBI-Ab) and the immunoglobulins stimulating the thyroid adenylate cyclase (TS-Ab). The present study was performed in 75 hyperthyroid Graves' patients to ascertain the pathophysiological significance of these immunoglobulins. TS-Ab and TBI-Ab prevalence appeared to be much higher in the untreated and in relapsing patients than in subjects in remission. When the results of TBI-Ab and TS-Ab were compared in each group of patients no correlation was found between the two activities. We conclude that the TBI-Ab and the TS-Ab are the markers of hyperthyroidism in Graves' disease but the two activities are not equivalent and probably reflect a different phenomenon concomitantly produced.     

A case of Graves' disease associated with an autonomously functioning thyroid nodule (AFTN) (Marine-Lenhalt syndrome) which spontaneously became a cold nodule

We report a 31-year-old female with Graves' disease associated with an autonomously functioning thyroid nodule (AFTN) (Marine-Lenhalt syndrome) in which the AFTN spontaneously became a cold nodule. Initially the patient was thyrotoxic and had diffuse goiter with an elevated radioiodine uptake. She became euthyroid following six months of antithyroid drug therapy, and in addition to diffuse goiter, the solitary hot nodule was palpable in the left lobe. Fourteen months later, hyperthyroidism recurred and the thyroid scan revealed diffuse radioiodine uptake with a cold area in the nodular region. The resected nodule showed extensive degeneration and the histological diagnosis was follicular adenoma with Graves' disease. We discussed the significance of recognizing the syndrome and also compared the frequency of spontaneous degeneration in AFTN and in solitary cold nodules.     

Variation of the thyrotropin-releasing-hormone (TRH) stimulated thyrotropin (TSH) response in comparison with the tyhroid-gland-suppression test and the triiodothyronine (T3) and thyroxine (T4) blood levels in the so-called euthyroid endocrine ophthalmopathy]

21 patients with active signs of euthyroid Graves' disease were given 400 mug thyrotropin-releasing hormone (TRH) i.v. All subjects with unresponsiveness to TRH had a nonsuppressible thyroidal 131I-uptake. On the basis of serum total T3 14 patients were hyperthyroid, 2 more had an elevated value of free T3. 4 patients with normal total T3 and nonsuppressible 131I-uptake were unresponsive to TRH, in 2 of them the free T3 fraction was elevated, however. 4 subjects with nonsuppressible 131I-uptake had a TRH stimulated TSH response. 2 of these subjects had hyperthyroid values of free and total T3 in serum and responded to TRH with an exaggerate TSH increment. The variations of TRH responsiveness may demonstrate a different threshold of the pituitary and the peripheral T3 receptors.     

Stopover and fat deposition by North American wood-warblers (Parulinae) following spring migration over the Gulf of Mexico

Summary Length of stopover and rate of weight gain (fat deposition) were studied in several species of passerine birds that stopped in southwestern Louisiana along the northern coast of the Gulf of Mexico after a trans-Gulf flight. Fatdepleted birds were more common among the birds that arrived at our study site in southwest Louisiana, though variability characterized our samples. Migrants that landed after encountering opposing winds or rain over the northern Gulf of Mexico were, on average, fatter than migrants that landed when weather was favorable for continued migration. Some of the variation in the energetic condition of arrivals may be explained by the location where migrants initiated crossings. Our simulation of flight over the Gulf of Mexico showed that with following winds a warbler can cross the Gulf of Mexico from Yucatan with fat reserves to spare, and stronger tailwinds make flights from as far south as Honduras energetically permissible. The length of stay after a trans-Gulf flight was related to the extent of fat-depletion upon arrival: lean birds stayed longer than fat migrants. Migrants stopped over for 1–7 days and replenished energy reserves at rates that varied from 0.19 g/d for Hooded Warblers (Wilsonia citrina) to 0.87 g/d for Ovenbirds (Seiurus aurocapillus). Within each species, most individuals gained weight at a rapid rate, though a few individuals lost or maintained weight during their stay.     

Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in patients with Graves' disease, subacute thyroiditis, and silent thyroiditis: a longitudinal study.

Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity was measured longitudinally in 12 patients with Graves' disease, 5 patients with subacute thyroiditis, and 1 patient with silent thyroiditis, and compared with that of 36 normal controls. The patients with Graves' disease and subacute thyroiditis were treated with anti-thyroid drug (methimazole or propylthiouracil) and prednisolone, respectively. On the other hand, no treatment was given to the patient with silent thyroiditis. Since two patients with Graves' disease clearly showed transient deterioration of the thyroid function during the treatment period, data from these two patients were separately investigated. Urinary levels of NAG in the remaining ten patients with Graves' disease before, 1, 3, 6 and 12 months after the treatment were 15.59 +/- 7.93 (SD), 8.96 +/- 6.82, 4.39 +/- 2.33, 3.46 +/- 2.24, and 3.63 +/- 2.38 U/g.creatinine (g.Cr.), respectively. Those obtained before, 1 and 3 months after the treatment were significantly higher than those of the controls (2.85 +/- 1.12 U/g.Cr.). Free thyroid hormone levels became normal or low 3 months after the treatment. The two Graves' patients mentioned above showed a transient increase in urinary NAG with concomitant changes in free thyroid hormone levels. Urinary NAG levels in the patients with subacute thyroiditis before, 2, 4, and 6 weeks after the treatment were 16.56 +/- 10.97, 6.76 +/- 2.79, 3.14 +/- 0.48 and 3.70 +/- 1.44 U/g.Cr., respectively. Those obtained before and 2 weeks after the treatment were significantly higher than those of the controls. Free thyroid hormones were normal 2 weeks after therapy. Urinary NAG in the patient with silent thyroiditis was 9.60 U/g.Cr. on the first visit and gradually decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serotoninergic polymorphisms (5-HTTLPR and 5-HT2A): association studies with psychosis in Alzheimer disease

Patients with Alzheimer disease (AD) often exhibit psychotic symptoms associated with cognitive impairment. A few association studies have been carried out to determine if the serotonin transporter and receptor genes are potential risk factors for AD and/or associated psychopathology. The aim of this study was to investigate the association of a serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the 5-HT2A receptor T102C polymorphism with the risk of developing dementia and/or psychotic symptoms in a group of sporadic AD patients from Italy. No significant differences in the distribution of allele and genotype frequencies of 5-HTTLPR and 5-HT2A T102C were found between patient and control groups. However, a significant association between the C102/C102 5-HT2A genotype and psychotic symptoms (p < 0.001) was observed. Our data strongly confirm results from previous studies suggesting that the C102 allele of the 5-HT2A receptor is associated with the occurrence of psychotic symptoms in AD. On the contrary, the serotonin transporter does not appear to be a major susceptibility factor in the pathophysiology of the disease.