Identification of Rosellinia species as producers of cyclodepsipeptide PF1022 A and resurrection of the genus Dematophora as inferred from polythetic taxonomy.

Rosellinia (Xylariaceae) is a large, cosmopolitan genus comprising over 130 species that have been defined based mainly on the morphology of their sexual morphs. The genus comprises both lignicolous and saprotrophic species that are frequently isolated as endophytes from healthy host plants, and important plant pathogens. In order to evaluate the utility of molecular phylogeny and secondary metabolite profiling to achieve a better basis for their classification, a set of strains was selected for a multi-locus phylogeny inferred from a combination of the sequences of the internal transcribed spacer region (ITS), the large subunit (LSU) of the nuclear rDNA, beta-tubulin (TUB2) and the second largest subunit of the RNA polymerase II (RPB2). Concurrently, various strains were surveyed for production of secondary metabolites. Metabolite profiling relied on methods with high performance liquid chromatography with diode array and mass spectrometric detection (HPLC-DAD/MS) as well as preparative isolation of the major components after re-fermentation followed by structure elucidation using nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry (HR-MS). Two new and nine known isopimarane diterpenoids were identified during our mycochemical studies of two selected Dematophora strains and the metabolites were tested for biological activity. In addition, the nematicidal cyclodepsipeptide PF1022 A was purified and identified from a culture of Rosellinia corticium, which is the first time that this endophyte-derived drug precursor has been identified unambiguously from an ascospore-derived isolate of a Rosellinia species. While the results of this first HPLC profiling were largely inconclusive regarding the utility of secondary metabolites as genus-specific chemotaxonomic markers, the phylogeny clearly showed that species featuring a dematophora-like asexual morph were included in a well-defined clade, for which the genus Dematophora is resurrected. Dematophora now comprises all previously known important plant pathogens in the genus such as D. arcuata, D. bunodes, D. necatrix and D. pepo, while Rosellinia s. str. comprises those species that are known to have a geniculosporium-like or nodulisporium-like asexual morph, or where the asexual morph remains unknown. The extensive morphological studies of L.E. Petrini served as a basis to transfer several further species from Rosellinia to Dematophora, based on the morphology of their asexual morphs. However, most species of Rosellinia and allies still need to be recollected in fresh state, cultured, and studied for their morphology and their phylogenetic affinities before the infrageneric relationships can be clarified.

Atypical Post-Injection Reactions with Delayed Onset Following Glatiramer Acetate 40 mg: Need for Titration?

BACKGROUND: Glatiramer acetate (GA) 20 mg/day (GA20) is associated with immediate post-injection reactions (PIRs). For convenience of use, approved GA 40 mg three times weekly (GA40) delivers a similar weekly dose. The dose and concentration of a single GA40 injection are, however, twice as high as for GA20, and post-injection adverse events may differ. Cases of atypical PIRs to GA40 prompted us to systematically monitor such events. OBJECTIVE: The aim was to characterize atypical PIRs in multiple sclerosis (MS) patients treated with GA40. METHODS: Clinical practice data were prospectively collected in consecutive relapsing-remitting MS patients. Descriptive statistics for categorical and continuous variables, Mann-Whitney and Chi-squared tests for baseline comparisons, and Cox regression models for association of variables to first atypical PIRs were applied. RESULTS: Forty-six out of 173 patients (26.6%) given GA40 experienced any PIRs. Of those, 38 (22.0%) had atypical, 14 (8.1%) had combined typical and atypical, and 26 (15.0%) had recurrent atypical PIRs, most frequently shivering (13.3%) and nausea/vomiting (8.1%). Compared to typical PIRs, onset of atypical PIRs was significantly delayed (median 30 vs 1 min, p < 0.0001), and their median duration longer (median 120 vs 6 min, p = 0.00013). Previous exposure to GA20 was associated with a lower risk of atypical PIRs [hazard ratio (HR) = 0.35, 95% confidence interval (CI) 0.17-0.72, p = 0.0039]. Patients experiencing PIRs with GA20 were at elevated risk for atypical PIRs with GA40 (HR = 5.75, 95% CI 1.66-19.94, p = 0.0059). CONCLUSIONS: Atypical PIRs with GA40, especially gastrointestinal symptoms and/or fever/shivering, had a delayed onset and occurred in a significant proportion of our patients. Their real prevalence should be assessed in appropriately designed studies accounting for  nocebo responses. Initial dose titration might reduce PIR frequency.

Determinação dos compostos fenólicos e da capacidade antioxidante de extratos aquosos e etanólicos de Jambolão (Syzygium cumini L. ) / Determination of phenolic compounds and antioxidant capacity of aqueous and ethanolic extracts of Jambul (Syzygium cumini)

RESUMO: A espécie Syzygium cumini conhecida como Jambolão é uma das plantas mais utilizadas na medicina popular principalmente no tratamento de febre, estomalgia, gastropatia e diabetes mellitus tipo 2. O rendimento extrativo de compostos bioativos, e mesmo sua propriedade farmacológica, no caso, a capacidade de desativação de radicais livres, são influenciados pelo método e solvente utilizados. No presente estudo foi avaliado o efeito de extração aquosa a quente e a frio, e as extrações hidroalcoólicas em quatro diferentes concentrações de etanol, de folhas e frutos de Jambolão em diferentes estágios de maturação. A quantificação de compostos fenólicos dos extratos foi realizada pelo método de Folin-Ciocalteau, enquanto o método para avaliar a atividade antirradical livre foi realizado através da capacidade de desativação do radical DPPH●. As folhas apresentaram maior quantidade de compostos fenólicos totais (237,52 mg. EAG100 g-1) em relação a qualquer dos cinco extratos dos frutos, independente do estágio de maturação destes. Entre os extratos dos frutos, aquele proveniente de frutos verdes apresentou maior quantidade de compostos fenólicos (109,17 mg.EAG100 g-1). A extração hidro-etanólica a 50% de etanol promoveu os maiores conteúdos de fenóis totais, independente do material vegetal. A maior atividade antirradical livre encontrada dentre os extratos mais ricos em fenóis foi obtida com frutos verdes, IC50 = 2,27 mg.mL-1, a partir da infusão a quente por 30 minutos. Nos extratos de folhas, a maior atividade antirradical livre encontrada foi IC50= 23,07 mg.mL-1 proveniente do extrato hidro-etanólico a 50 % (v/v)

ABSTRACT: Determination of phenolic compounds and antioxidant capacity of aqueous and ethanolic extracts of Jambul (Syzygium cumini). The species Syzygium cumini, known as Jambul, is one of the most used species in folk medicine because of the possible anti-inflammatory and hypoglycemic activity from its extracts. Studies looking for bioactive compounds in several species have tested many extraction methods evaluating the capacity of sequestration of different types of compounds. In the present study, the effects of hot and cold extraction, as well as hydroalcoholic extraction at four different concentrations were evaluated, using as plant material leaves and fruits at different stages of maturation. The content of phenolic compounds of the obtained extracts was evaluated by the Folin-Ciocalteu method, as well as the antiradical activity by the DPPH● scavenging capacity. Analyzing the five different stages of fruit ripening compared to leaves, it was observed that the leaves had higher averages in the amounts of phenolic compounds (237.52 mg GAE 100 g-1) compared to the fruit, being the greenest fruit the one that had the highest amount of phenolic compounds (109.17 mg GAE 100 g-1) when compared to the other stages of maturation tested. The extraction using 50% ethanol showed the best phenol results regardless of the plant material used. The antioxidant activity in the best results for phenols showed a higher antioxidant activity for green fruits (IC50 2.27 mg.mL-1) compared to the leaves (IC50 23.07 mg.mL-1) regardless of the extract type used

Electrical low-frequency stimulation induces central neuroplastic changes of pain processing in man.

Electrical low-frequency stimulation (LFS) inhibits pain perception and nociceptive processing as shown by psychophysical and electrophysiological means (long-term depression, LTD). Information regarding central mechanisms involved in LTD induction and maintenance are still missing. This study hypothesizes that electrical LFS induces changes in activation pattern of pain-related brain areas. Thirty-two electrophysiological and psychophysical experiments were performed in 16 healthy volunteers. Painful electrical test stimulation (0.125 Hz, 60 pulses) and conditioning LFS (1 Hz, 1200 pulses) were applied by a concentric electrode to the right hand. Test stimulation series were performed before (Pre) and after LFS (Post) or no stimulation period (Control). Volunteers rated pain perception according to a verbal rating scale (0-100). Somatosensory evoked cortical potentials were recorded with 64-channel electroencephalography. Individual dipole source modeling using CURRY software (Compumedics, Hamburg, Germany) yielded information about dipole location and strength. The strongest decrease in LFS-induced pain perception was shown after LFS (p < 0.01). Topographic distribution of cortical potentials revealed reproducible negative (N1, N2) and positive (P2) components. Dipole magnitude analysis showed a significant difference between Post LFS and Post Control for P2 (p < 0.01). P2 dipole location analysis yielded a significant posterior (p < 0.05) shift following LTD induction. Thus, data reveal central changes of pain processing after LTD induction. These experiments may help judging the potency of LTD as model for electrostimulation in future analgesic therapy.

Deployment of self-expandable stents in aneurysmatic cerebral vessels: comparison of different computational approaches for interventional planning.

In the last few years, there has been a growing focus on faster computational methods to support clinicians in planning stenting procedures. This study investigates the possibility of introducing computational approximations in modelling stent deployment in aneurysmatic cerebral vessels to achieve simulations compatible with the constraints of real clinical workflows. The release of a self-expandable stent in a simplified aneurysmatic vessel was modelled in four different initial positions. Six progressively simplified modelling approaches (based on Finite Element method and Fast Virtual Stenting--FVS) have been used. Comparing accuracy of the results, the final configuration of the stent is more affected by neglecting mechanical properties of materials (FVS) than by adopting 1D instead of 3D stent models. Nevertheless, the differences showed are acceptable compared to those achieved by considering different stent initial positions. Regarding computational costs, simulations involving 1D stent features are the only ones feasible in clinical context.

Continuum damage model for bioresorbable magnesium alloy devices - Application to coronary stents.

The main drawback of a conventional stenting procedure is the high risk of restenosis. The idea of a stent that "disappears" after having fulfilled its mission is very intriguing and fascinating, since it can be expected that the stent mass decreases in time to allow the gradual transmission of the mechanical load to the surrounding tissues owing to controlled dissolution by corrosion. Magnesium and its alloys are appealing materials for designing biodegradable stents. The objective of this work is to develop, in a finite element framework, a model of magnesium degradation that is able to predict the corrosion rate, thus providing a valuable tool for the design of bioresorbable stents. Continuum damage mechanics is suitable for modeling several damage mechanisms, including different types of corrosion. In this study, the damage is assumed to be the superposition of stress corrosion and uniform microgalvanic corrosion processes. The former describes the stress-mediated localization of the corrosion attack through a stress-dependent evolution law, while the latter affects the free surface of the material exposed to an aggressive environment. Comparisons with experimental tests show that the developed model can reproduce the behavior of different magnesium alloys subjected to static corrosion tests. The study shows that parameter identification for a correct calibration of the model response on the results of uniform and stress corrosion experimental tests is reachable. Moreover, three-dimensional stenting procedures accounting for interaction with the arterial vessel are simulated, and it is shown how the proposed modeling approach gives the possibility of accounting for the combined effects of an aggressive environment and mechanical loading.

Finite element shape optimization for biodegradable magnesium alloy stents.

Biodegradable magnesium alloy stents (MAS) are a promising solution for long-term adverse events caused by interactions between vessels and permanent stent platforms of drug eluting stents. However, the existing MAS showed severe lumen loss after a few months: too short degradation time may be the main reason for this drawback. In this study, a new design concept of MAS was proposed and a shape optimization method with finite element analysis was applied on two-dimensional (2D) stent models considering four different magnesium alloys: AZ80, AZ31, ZM21, and WE43. A morphing procedure was utilized to facilitate the optimization. Two experiments were carried out for a preliminary validation of the 2D models with good results. The optimized designs were compared to an existing MAS by means of three-dimensional finite element analysis. The results showed that the final optimized design with alloy WE43, compared to the existing MAS, has an increased strut width by approximately 48%, improved safety properties (decreased the maximum principal stress after recoil with tissue by 29%, and decreased the maximum principal strain during expansion by 14%) and improved scaffolding ability (increased by 24%). Accordingly, the degradation time can be expected to extend. The used methodology provides a convenient and practical way to develop novel MAS designs.

The importance of stimulus parameters for the experience of the thermal grill illusion.

AIMS: This study aimed to investigate the quality of the thermal grill illusion (TGI) and the importance of stimulus parameters (distance between, and number of stimulation bars). MATERIAL AND METHODS: Twenty-one different stimuli were applied to a group of 19 healthy subjects on the glabrous skin over the palm and fingers. RESULTS: The TGI was found to be painful (19.42% on the palm; 17.98% on the fingers), mechanical (25.24% on the palm; 5.62% on the fingers), emotional (13.59% on the palm; 14.61% on the fingers) or unusual (42.72% on the palm; 61.8% on the fingers) sensations. A total of 89.5% (palm) and 94.4% (fingers) of the subjects reported TGI. Between 45% (fingers) and 50% (palm) of the stimuli elicited TGI. Neither the distance (2 approximately 10 mm) between adjacent warm (40 +/- 1 degrees C) and cold (20 +/- 1 degrees C) bars nor the number of the stimulation bars (2 approximately 6) significantly affected the occurrence of the TGI (N.S.). The average reaction time was 2.4 +/- 0.1 seconds to the TGI sensation. Females showed longer reaction time than males (P

Mechanical behaviour of nickel-titanium rotary endodontic instruments in simulated clinical conditions: a computational study.

AIM: To develop an accurate finite element (FE) model for studying rotary endodontic instruments and to demonstrate the usefulness of the FE method in improving the knowledge of the mechanical behaviour of these instruments during root canal preparation. METHODOLOGY: An accurate geometrical model of a Ni-Ti ProTaper F1 instrument was created. The interaction between the rotating instrument and differently shaped root canals during the insertion and removal procedure was studied using FE analyses. The complex thermo-mechanical behaviour of the Ni-Ti alloy was reproduced using an ad hoc computational subroutine. With the aim of demonstrating the enhanced performance of the shape memory alloy employment, the same analysis was performed on a 'virtual' ProTaper F1 made of stainless steel. RESULTS: The Ni-Ti instrument operated in its pseudo-elastic range and was able to recover its original shape and to follow the canal curvature without deviation. The radius and the position of the canal curvature are the most critical parameters that determined the stress in the instrument with higher stress levels being produced by decreasing the radius and moving from the apical to the mid root position. CONCLUSIONS: The most demanding working conditions were observed in canals with sharp curves, especially in areas where the instruments had larger diameters. To prevent possible damage to instruments and fracture, it is advised that the instruments should be discarded following their use in such canals.

Production and regeneration of protoplasts from Gremmeniella abietina and Ascocalyx abietis.

This work was undertaken to develop a system of protoplast isolation and regeneration for G. abietina and A. abietis that could be of use for the genetic manipulation of both species. Nuclear staining was performed to assess the nuclear conditions of the protoplasts. Of the 19 enzyme complexes studied, only 10 were found to have some lytic effect on either Gremmeniella, A. abietis, or both. Only snail enzyme (from Szeged University), Novozym 234, lytic enzyme L1, or mixtures of snail enzyme and Novozym 234 produced satisfactory yields of protoplasts. Regeneration of protoplasts was observed on complete and on minimal medium, and occurred from protoplasts plated out directly onto the surface and from those embedded in the agarose. In most cases, embedding increased the frequency of regeneration. Protoplasts formed after incubation at 20 degrees C regenerated at a frequency of approximately 5%, as opposed to 2% for those produced at 30 degrees C. As roughly 40% of the protoplasts were anucleate, the percentage of regeneration can be estimated as about 12.5% at 20 degrees C and 5% at 30 degrees C. Protoplasting appears to be a satisfactory method of obtaining material for genetic experiments with G. abietina and A. abietis when other methods are not directly applicable.

Cardiac dysfunction in acromegaly: evidence by pulsed wave tissue Doppler imaging.

OBJECTIVE: To verify whether the accuracy of data on myocardial function provided by pulsed-wave tissue Doppler imaging (PWTDI), a new echocardiographic application that allows quantitative measurements of myocardial wall velocities, could help towards a better understanding of the natural history of acromegalic cardiomyopathy. DESIGN: Eighteen patients with active acromegaly (ten men and eight women; mean age 48.0+/-15.0 years) with no other detectable cause of heart disease underwent PWTDI. Thirteen healthy individuals matched for age and body mass index acted as a control group. METHODS: Ejection fraction (EF), transmitral early/late diastolic velocity (E/A) ratio and isovolumic relaxation time (IVRT) were measured by conventional echocardiography; systolic peak (Sv) and early (Ev) and late (Av) diastolic peak velocities, Ev/Av ratio and regional IVRT (IVRTs) were obtained by PWTDI. RESULTS: All patients showed appreciably abnormal left ventricular global diastolic function represented by prolongation of the IVRT (P<0.001). Using PWTDI we found a prolongation of IVRTs and inversion of the Ev/Av ratio. In addition, the Ev/Av ratio proved to be significantly negatively correlated with IVRT; this correlation was not present in the case of the E/A ratio. Furthermore, a decrease in Sv was detected in the basal segment of the lateral wall (P<0.01), which had the greatest degree of diastolic dysfunction. CONCLUSIONS: PWTDI confirmed the acknowledged diastolic dysfunction that accompanies acromegalic cardiomyopathy and highlighted the greater sensitivity of regional PWTDI with respect to global Doppler diastolic indexes. Furthermore, by revealing an impairment of regional systolic function in presence of a normal EF, the findings with PWTDI contradicted the largely accepted theory that systolic function remains normal for several years in patients affected by acromegalic cardiomyopathy.

Cardiac function, physical exercise capacity, and quality of life during long-term thyrotropin-suppressive therapy with levothyroxine: effect of individual dose tailoring.

As recently claimed, TSH-suppressive therapy with L-T4 may have adverse effects on the heart, but these results have not been consistently confirmed. We assessed cardiac function by clinical, echocardiographic, and ergometabolic criteria in 19 patients (16 women and 3 men) receiving long term L-T4 at a fixed daily dose ranging from 1.8-4.0 microg/kg. The results showed significant alterations in several cardiac parameters suggestive of subclinical hyperthyroidism. In particular, intraventricular septum thickness (10.0+/-1.4 vs. 8.1+/-1.1 mm), left ventricular posterior wall thickness (9.4 1.5 vs. 8.1+/-1.1 mm), end-diastolic dimension (47+/-4 vs. 44+/-3 mm), and left ventricular mass index (102+/-15 vs. 75+/-15 g/m2) were significantly increased compared to values in age- and sex-matched euthyroid controls. Exercise tolerance (expressed as maximal tolerated workload; 102+/-14 vs. 117+/-12 watts), maximal VO2 achieved at peak exercise (maximum VO2, 17.3+/-3.3 vs. 21.9+/-2.5 mL/min x kg), and anaerobic threshold (expressed as a percentage of VO2max, 46.5+/-8.4 vs. 56.2+/-6.6) were significantly reduced in L-T4-treated patients. The L-T4 dose was then reduced to the minimal amount able to keep the serum TSH concentration at 0.1 mU/L or less in 7 patients who were reevaluated 6 months after the initial study. This individual tailoring of the TSH-suppressive L-T4 dose was in all cases associated with normalization of all echocardiographic and ergometabolic parameters. In conclusion, our findings show that abnormalities of heart morphology associated with impaired exercise performance occur as a consequence of long term therapy with fixed TSH-suppressive doses of L-T4, but that these abnormalities improve or disappear after careful tailoring of TSH-suppressive therapy.

Lactose intolerance following antithyroid drug medications.

We recently observed 2 lactase-deficient women with Graves' disease who consistently developed severe diarrhea after ingestion of thionamide (methimazole and propylthiouracil) tablets containing lactose as carrier. The strict temporal relationship between ingestion of lactose-containing tablets and appearance of intestinal symptoms, as well as the absence of side effects following ingestion of methimazole tablets without lactose as carrier, provided the clue for the diagnosis. To our knowledge, severe diarrhea resulting from carrier lactose has not been previously reported for antithyroid drugs, and should be considered in occasional cases of patients with gastrointestinal symptoms on thionamide therapy.

Long-term treatment of Nelson's syndrome by octreotide: a case report.

Medical management of Nelson's syndrome by drugs such as bromocriptine, sodium and magnesium valproate has provided disappointing or, at least, controversial results. We report here on the results of long-term (2 yr) treatment with the somatostatin analogue octreotide (300 micrograms daily sc) in one patient affected by Nelson's syndrome occurring after bilateral adrenalectomy for Cushing's syndrome. During treatment, skin hyperpigmentation and serum ACTH levels decreased dramatically and a slight (about 10%) reduction in tumor size, as assessed by computerized tomography, was also observed. These results suggest that octreotide may be useful for the medical management of Nelson's syndrome.

Fungal endophytes from the leaves and twigs of Quercus ilex L. from England, Majorca and Switzerland.

Leaves of Quercus ilex taken from sites in England, Majorca and Switzerland have been studied to detect the influence of the geographic position of the host within and outside its native range on the composition of its endophytic fungal assemblages. Samples of stem tissue of Q. ilex collected from the Swiss trees were also studied to confirm tissue-specific differences. Sixty different fungal taxa were isolated, but only 28 were frequent. Of the total number of isolates from the leaves from the Swiss, British and Spanish sites 87%, 31% and 63%, respectively, were coelomycetes. Four species of Phomopsis, which includes Phyllosticta ilicina (=Phomopsis ilicina v. d. Aa, ined.), were the most frequent endophytes of leaves and were either absent or rare in the twig units. Two distinct kinds of sterile mycelia were common in twigs. Swiss and Spanish trees possessed fungal assemblages distinct from those present in Britain. Naturalized stands were distinguished from native stands by the presence of rather cosmopolitan and non-specific fungal taxa, rare or absent in the samples collected in the native stands. Samples derived from the native stands were colonized by more host-specific fungi. The relative frequency of two sterile mycelia in the Swiss and Spanish sites determined their separation. Phyllosticta (Phomopsis) ilicina, the most numerous leaf colonizer, was virtually absent from the bark and the xylem. The frequent occurrence of coelomycetes as endophytes of woody trees is briefly discussed.

Octreotide treatment does not affect the size of most non-functioning pituitary adenomas.

The somatostatin analogue, octreotide (OC) has commonly been used in the management of growth hormone- and thyrotropin-secreting pituitary tumors, and shown to be effective both on hormone production and tumor size. Because OC receptors may be expressed also in some nonfunctioning pituitary adenomas, it has been postulated that OC might play a role in the treatment of these tumors as well. In the present study, the morphological effects of OC administration, as assessed by computer tomography (CT) scan, were evaluated in 8 patients (5 men, 3 women, age range 25-79 yr) affected by non-functioning pituitary tumors. The drug was given sc at the dose of 100 micrograms tid for 3-6 months. No significant change in visual field or tumor size occurred after OC treatment in 7 patients, whereas one showed a significant improvement of visual field associated with a decreased tumoral mass. These data suggest that OC is not an effective drug in the management of nonfunctioning pituitary adenomas.

[Acromegalic arthropathy]. / L'artropatia acromegalica.

Six acromegalic patients, three males (aged 28 to 48 years) and three females (aged 57 to 75 years), with GH-producing pituitary adenoma, were studied through clinical examination, laboratory and instrumental tests. In all the patients frequent involvement of large joints, with crepitus and provoked pain, was found; while articular mobility was normal especially in the dorso-lumbar spine, a frequent seat of pain. Radiology showed typical features of an osteoarthritic process with characteristic widening of articular spaces, especially in weight-bearing large joints in symptomatic patients. The evolution of this arthropathy lead to anatomo-clinical pictures almost indistinguishable from osteoarthritis; however, in the early stages, the marked cartilaginous hypertrophy is responsible for peculiar anatomo-radiological pictures, principally represented by widening of articular spaces and intervertebral discal spaces, especially in the dorso-lumbar spine. As far as bone metabolism is concerned, neoproduction and reabsorption, both increased, proceed simultaneously; bone mass reduction is described in some segments. In our study, the two patients with active acromegaly showed bone mass reduction in the lumbar spine.

Percutaneous intranodular ethanol injection for treatment of autonomously functioning thyroid nodules.

BACKGROUND: The aim of the study is the assessment of percutaneous intranodular ethanol injection (PNEI) as an alternative therapeutic procedure to classic surgery and radioiodine administration in autonomously functioning thyroid nodule treatment. METHODS: Thirty-seven patients with hot nodules (18 pretoxic and 19 toxic) have been treated by means of PNEI under ultrasonographic guide. Ninety-five percent ethanol in a mean dose of 25 ml has been used. RESULTS: Nearly 80% of the patients showed normalization of thyroid-stimulating hormone levels and a complete recovery of extranodular tissue at scintiscan. All nodules decreased strikingly in size, many becoming undetectable. Mild and transient side effects were seen in 9% of the patients. CONCLUSIONS: PNEI seems to be a feasible procedure on outpatients. It is safe when performed by a well-trained staff using ultrasonographic control. It may be carried out at any age and in patients at risk for surgery. PNEI can be considered a useful alternative to surgery and radioiodine administration in all autonomously functioning thyroid nodules and particularly in pretoxic nodules.

Therapy of Graves' disease with sodium ipodate is associated with a high recurrence rate of hyperthyroidism.

To evaluate the long-term efficacy of sodium ipodate (IPO) in the treatment of hyperthyroid Graves' disease, we studied 12 consecutive patients with Graves' hyperthyroidism treated only with 500 mg IPO po daily for several weeks to 22 months. Serum thyroid hormone concentrations markedly decreased and serum free T3 values normalized in all patients within 7 days of therapy. Five patients (42%, Group 1) were euthyroid after 6 weeks of IPO treatment and remained so until IPO was discontinued after 22 months. Recurrence of hyperthyroidism after drug withdrawal occurred in only one of these Group 1 patients, who was promptly responsive to a second course of IPO. In contrast, seven of 12 patients (58%, Group 2) relapsed with recurrent hyperthyroidism between 14 and 42 days of IPO therapy. After IPO was withdrawn, these Group 2 patients were treated with methimazole (20-30 mg/day, initial dose), but the therapeutic response was poor and delayed. Two patients were still hyperthyroid after 6 months of methimazole treatment. Elevated serum FT3 concentrations were observed in the Group 2 patients at 21 days following the early normalization of serum FT3 concentrations. No changes in serum thyroglobulin and thyroid microsomal and TSH-receptor autoantibody titers were observed in either groups during IPO therapy. In conclusion, the results of the present study demonstrate that IPO rapidly restores euthyroidism, but its prolonged administration is associated with a high rate of relapse of hyperthyroidism and a poor response to subsequent methimazole treatment and that long-term IPO administration does not affect humoral markers of thyroid autoimmunity.