Electrocardiogram analysis in Anderson-Fabry disease: a valuable tool for progressive phenotypic expression tracking.

Background: Electrocardiogram (ECG) has proven to be useful for early detection of cardiac involvement in Anderson-Fabry disease (AFD); however, little evidence is available on the association between ECG alterations and the progression of the disease. Aim and Methods: To perform a cross sectional comparison of ECG abnormalities throughout different left ventricular hypertrophy (LVH) severity subgroups, providing ECG patterns specific of the progressive AFD stages. 189 AFD patients from a multicenter cohort underwent comprehensive ECG analysis, echocardiography, and clinical evaluation. Results: The study cohort (39% males, median age 47 years, 68% classical AFD) was divided into 4 groups according to different degree of left ventricular (LV) thickness: group A ≤ 9 mm (n = 52, 28%); group B 10-14 mm (n = 76, 40%); group C 15-19 mm (n = 46, 24%); group D ≥ 20 mm (n = 15, 8%). The most frequent conduction delay was right bundle branch block (RBBB), incomplete in groups B and C (20%,22%) and complete RBBB in group D (54%, p < 0.001); none of the patients had left bundle branch block (LBBB). Left anterior fascicular block, LVH criteria, negative T waves, ST depression were more common in the advanced stages of the disease (p < 0.001). Summarizing our results, we suggested ECG patterns representative of the different AFD stages as assessed by the increases in LV thickness over time (Central Figure). Patients from group A showed mostly a normal ECG (77%) or minor anomalies like LVH criteria (8%) and delta wave/slurred QR onset + borderline PR (8%). Differently, patients from groups B and C exhibited more heterogeneous ECG patterns: LVH (17%; 7% respectively); LVH + LV strain (9%; 17%); incomplete RBBB + repolarization abnormalities (8%; 9%), more frequently associated with LVH criteria in group C than B (8%; 15%). Finally, patients from group D showed very peculiar ECG patterns, represented by complete RBBB + LVH and repolarization abnormalities (40%), sometimes associated with QRS fragmentation (13%). Conclusions: ECG is a sensitive tool for early identification and long-term monitoring of cardiac involvement in patients with AFD, providing "instantaneous pictures" along the natural history of AFD. Whether ECG changes may be associated with clinical events remains to be determined.

The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat.

This study has evaluated the effect of EVOO (Extra-Virgin olive oil), OA (oleic acid) and HT (hydroxytyrosol) in an induced model of MS through experimental autoimmune encephalomyelitis (EAE).Dark Agouti 2-month old rats (25 males) were divided into five groups: (i) control group, (ii) EAE group, (iii) EAE+EVOO, (iv) EAE+HT, and (v) EAE+OA. At 65 days, the animals were sacrificed and the glutathione redox system and bacterial lipopolysaccharide (LPS) and LPS-binding protein (LBP) products of the microbiota in brain, spinal cord, and blood were evaluated.Gastric administration of EVOO, OA, and HT reduced the degree of lipid and protein oxidation, and increased glutathione peroxidase, making it a diet-based mechanism for enhancing protection against oxidative damage. In addition, it reduced the levels of LPS and LBP, which appeared as being increased in the EAE correlated with the oxidative stress produced by the disease.

Author Correction: Unsupervised Scalable Statistical Method for Identifying Influential Users in Online Social Networks.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Unsupervised Scalable Statistical Method for Identifying Influential Users in Online Social Networks.

Billions of users interact intensively every day via Online Social Networks (OSNs) such as Facebook, Twitter, or Google+. This makes OSNs an invaluable source of information, and channel of actuation, for sectors like advertising, marketing, or politics. To get the most of OSNs, analysts need to identify influential users that can be leveraged for promoting products, distributing messages, or improving the image of companies. In this report we propose a new unsupervised method, Massive Unsupervised Outlier Detection (MUOD), based on outliers detection, for providing support in the identification of influential users. MUOD is scalable, and can hence be used in large OSNs. Moreover, it labels the outliers as of shape, magnitude, or amplitude, depending of their features. This allows classifying the outlier users in multiple different classes, which are likely to include different types of influential users. Applying MUOD to a subset of roughly 400 million Google+ users, it has allowed identifying and discriminating automatically sets of outlier users, which present features associated to different definitions of influential users, like capacity to attract engagement, capacity to attract a large number of followers, or high infection capacity.

Radiofrecuencia pulsada del ganglio de la raíz dorsal torácico con catéter epidural. Un nuevo abordaje de un tratamiento efectivo / Pulsed radiofrequency of the thoracic dorsal root ganglion with epidural catheter-electrode. A new approach for an effective treatment

La radiofrecuencia pulsada (RFp) se ha utilizado para el tratamiento de nervios periféricos y del ganglio de la raíz dorsal (GRD). Comúnmente se ha aplicado para tratamiento de dolor lumbar, cervical y neuropatías con muy buenos resultados. El ganglio de la raíz dorsal es una estructura anatómica que se encuentra situada bilateralmente en el extremo distal de la raíz dorsal en el espacio epidural lateral. La mayor parte de los GRD torácicos se localizan en la parte craneal medial de los agujeros intervertebrales. Los pacientes con dolor torácico irradiado siguiendo un patrón segmentario, que no responden al tratamiento conservador, son susceptibles de tratamiento mediante RFp del GRD. Con el objetivo de salvar las dificultades técnicas en el acceso al GRD torácico y de minimizar las posibles complicaciones yatrogénicas derivadas de la técnica percutánea tradicional, decidimos realizar la técnica de RFp en GRD a nivel torácico con catéter epidural mediante abordaje del espacio epidural vía translaminar en dos pacientes afectos de radiculopatía torácica. El tratamiento del ganglio de la raíz dorsal a nivel lumbar es una terapia muy extendida en pacientes con dolor crónico lumbar radicular. Diversos estudios y revisiones avalan la realización de esta técnica. Sin embargo, el dolor radicular torácico no es un síndrome clínico típico como en el área lumbar. Existen diferentes patrones dolorosos: dolor constante o intermitente, dolor nociceptivo o neuropático o una combinación de estos. El cuestionario de dolor "Pain detect" fue específicamente desarrollado para detectar los componentes del dolor neuropático en adultos. El tratamiento del GRD mediante RFp con abordaje epidural realizado en los casos descritos ha demostrado ser efectivo. Hemos obtenido una buena tasa de éxitos con una disminución en la EVN de más del 50 % en los dos casos, con la práctica desaparición del componente neuropático del dolor. El abordaje a través del canal epidural vía translaminar aporta gran seguridad emergiendo como una opción adecuada para disminuir la tasa de complicaciones graves (AU)

Pulsed radiofrequency (pRF) has been used for the treatment of peripheral nerves and the dorsal root ganglion (DRG). It has been commonly applied for the treatment of low back pain, neck pain and neuropathies with very good results. The dorsal root ganglion is an anatomical structure that is located bilaterally at the distal end of the dorsal root in the lateral epidural space. Most of the thoracic GRDs are located in the medial cranial part of the intervertebral foramina. Patients with thoracic pain radiated following a segmental pattern, which do not respond to conservative treatment, are susceptible to treatment by pRF from the DRG. In order to overcome the technical difficulties in access to thoracic GRD and to minimize the possible iatrogenic complications derived from the traditional percutaneous technique, we decided to perform the pRF technique in GRD at the thoracic level with epidural catheter by approaching the epidural space via translaminar in two patients with thoracic radiculopathy. Treatment of the dorsal root ganglion at the lumbar level is a widespread therapy in patients with chronic low back pain. Various studies and reviews support the realization of this technique. However, thoracic radicular pain is not a typical clinical syndrome such as in the lumbar area. There are different pain patterns: constant or intermittent pain, nociceptive or neuropathic pain or a combination of these. The PAIN DETECT questionnaire was specifically developed to detect the components of neuropathic pain in adults. Treatment of DRG using pRF with an epidural approach performed in the cases described has been shown to be effective. We obtained a good success rate with a decrease in NRS of more than 50% in both cases, with the practical disappearance of the neuropathic component of pain. The approach through the epidural canal via translaminar provides great safety emerging as an adequate option to decrease the rate of serious complications (AU)

[Venous thromboembolism in pregnancy: current state of the art]. / Tromboembolismo venoso in gravidanza: attuale stato dell'arte.

Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during pregnancy or early after delivery and it remains a diagnostic and therapeutic challenge. The latest Confidential Enquiry into Maternal Deaths (2006-2008) showed that VTE is now the third leading cause of direct maternal mortality, beside sepsis and hypertension. In particular the prevalence of VTE has been estimated to be 1 per 1000-2000 pregnancies. The risk of VTE is five times higher in a pregnant woman than in non-pregnant woman of similar age and postpartum VTE is more common than antepartum VTE. A literature search was carried out on Pubmed using the following key words: "venous thromboembolism", "pregnancy", "risk factors", "prophylaxis", "anticoagulants". Studies from 1999 onwards were analyzed. This review aimed to provide an update of whole current literature on VTE in pregnancy highlighting the most recent findings in diagnostic and therapeutic strategies, considering in detail risks and benefits of various techniques and drug classes, for both mother and fetus. Large trials of anticoagulants administration in pregnancy are lacking and recommendations are mainly based on case series and on expert opinions. Nonetheless, anticoagulants are believed to improve the outcome of pregnancy for women with current or previous VTE.

Acclimation to decompression sickness in rats.

Protection against decompression sickness (DCS) by acclimation to hyperbaric decompression has been hypothesized but never proven. We exposed rats to acclimation dives followed by a stressful "test" dive to determine whether acclimation occurred. Experiments were divided into two phases. Phase 1 rats were exposed to daily acclimation dives of hyperbaric air for 30 min followed by rapid decompression on one of the following regimens: 70 ft of seawater (fsw) for 9 days (L70), 70 fsw for 4 days (S70), 40 fsw for 9 days (L40), 40 fsw for 4 days (S40), or unpressurized sham exposure for 9 days (Control). On the day following the last exposure, all were subjected to a "test" dive (175 fsw, 60 min, rapid decompression). Both L70 and S70 rats had significantly lower incidences of DCS than Control rats (36% and 41% vs. 62%, respectively). DCS incidences for the other regimens were lower than in Control rats but without statistical significance. Phase 2 used the most protective regimen from phase 1 (L70); rats were exposed to L70 or a similar regimen with a less stressful staged decompression. Another group was exposed to a single acclimation dive (70 fsw/30 min) on the day before the test dive. We observed a nonsignificant trend for the rapidly decompressed L70 dives to be more protective than staged decompression dives (44% vs. 51% DCS incidence). The single acclimation dive regimen did not provide protection. We conclude that protection against DCS can be attained with acclimating exposures that do not themselves cause DCS. The deeper acclimation dive regimens (70 fsw) provided the most protection.

Randomized clinical trial to evaluate the effects of perioperative supplemental oxygen administration on the colorectal anastomosis.

BACKGROUND: Perioperative supplemental oxygen therapy may have beneficial effects on wound healing following colorectal surgery. The aim of this study was to evaluate the effects of such therapy on colorectal anastomotic pH and partial pressure of carbon dioxide (PCO(2)) gap. METHODS: Forty-five patients undergoing anterior resection for rectal or sigmoid cancer were randomized to receive 30 or 80 per cent perioperative oxygen. Administration was commenced after induction of anaesthesia and maintained for 6 h after surgery. Intragastric and anastomotic tonometric catheters were placed in each patient and intramucosal pH (pHi) was measured immediately after operation, and 6 and 24 h later. Gastric and anastomotic pHi and PCO(2) gap in each group were compared. RESULTS: There was a significantly lower anastomotic pHi and wider PCO(2) gap for gastric readings in the 30 per cent O(2) group, both 30 min (pHi, P = 0.006; PCO(2) gap, P = 0.006) and 6 h (pHi, P = 0.024; PCO(2) gap, P = 0.036) after surgery. There were no differences 24 h after surgery while breathing room air (pHi, P = 0.131; PCO(2) gap P = 0.139). No difference was found between gastric and anastomotic readings at any time point in the 80 per cent O(2) group. CONCLUSION: Perioperative administration of 80 per cent O(2) both during surgery and for 6 hours afterwards is associated with an improvement in relative anastomotic hypoperfusion as assessed by the measurement of pHi and PCO(2) gap.

Four new HLA class I alleles in Cauacasoids.

Four new HLA classical class I alleles in the three loci are described in Caucasian individuals. A*3012 was first suspected by an abnormal serologic pattern that would be explained by the single amino acid substitution at the A30-specific Ser17. B*270505 differs from B*270502 in a silent substitution at an up to now constant position in the B locus. B*3541 encodes for a new Cys at position 118 that has not been encountered in neither human nor primate alleles. Cw*0716 seems to be originated by a large-scale interallelic recombination event between Cw*0701/*0706/*0718 and Cw*020202, giving rise to a new antigen-binding cleft conformation.

Sequencing of two new HLA class II alleles: DRB3*0218 and DQB1*030202.

Two novel human leukocyte antigen (HLA) class II alleles for DRB3 and DQB1 genes detected in Caucasoid Spanish individuals are described: DRB3*0218 and DQB1*030202. Both alleles have been found during routine high-resolution typing by sequencing. DRB3*0218 shows a novel DRB3 gene polymorphic position, located at amino acid residue 58, alanine to glutamic acid. This residue is shared by several DRB1 alleles, including all described DRB1*11 subtypes. DQB1*030202 differs from DQB1*030201 by a point mutation at position 319 (T to C). This nucleotide change generates a new codon at amino acid position 75 that is not shared by any other DQB1 allele.

A novel mutation in the calcium-sensing receptor responsible for autosomal dominant hypocalcemia in a family with two uncommon parathyroid hormone polymorphisms.

A novel missense activating mutation in the extracellular calcium-sensing receptor (CaSR) is reported in this work. It was identified in three related subjects with the phenotypic features of autosomal dominant hypocalcemia (ADH). The proband, a 27-year-old woman, diagnosed as having hypoparathyroidism at 7 years of age and a history of seizures, showed the highest penetrance of the mutation. The remaining two affected members presented asymptomatic chronic hypocalcemia despite severe hypoparathyroidism associated with high levels of serum phosphate and calcium urinary excretion. The missense mutation (Glu(604)Lys) affected an amino acid residue in the C terminus of the cysteine-rich domain of the extracellular amino-terminal domain, which seems to be required for the coupling of ligand binding to the activation of intracellular signaling pathways. This genetic change cosegregated with hypocalcemia in all the individuals where the mutation was found. As parathyroid hormone (PTH) secretion is the regulatory target of the CaSR, polymorphism analysis of the PTH gene was carried out. PTH polymorphisms were analyzed in the kindred studied. Affected members for the Glu(604)Lys CaSR mutation which also carried the uncommon PTH alleles showed higher penetrance of the mutation, with more severe autosomal dominant hypocalcemia. These results suggested that the PTH gene could act as a modifier locus of ADH, affecting the penetrance of the activating CaSR mutation described.

Purging of leukemia-contaminated bone marrow grafts using suicide adenoviral vectors: an in vivo murine experimental model.

Autologous bone marrow transplantation is an alternative therapeutic option for acute myeloid leukemia patients lacking a compatible donor. However, bone marrow from these patients may contain residual leukemic cells that should be ideally eliminated prior to the infusion of the graft. With the aim of developing more efficient protocols of graft purging, adenoviral-mediated gene transfer protocols have been conducted. We studied whether suicide adenoviral vectors expressing the cytosine deaminase gene (AdCD) could be used for selectively killing leukemic WEHI-3B cells. The AdCD transduction followed by the 5-fluorocytosine exposure abrogated the growth of WEHI-3B cells in vitro, with a minimal effect on normal hematopietic progenitors. To test the efficacy of the purging protocol in vivo, bone marrow cells were mixed with syngenic WEHI-3B cells and this chimeric cell population was transduced with AdCD vectors. Infected cells were injected into myeloablated Balb-c mice, which then received a 5-fluorocytosine treatment for 4 days. All mice transplanted with unpurged bone marrow developed leukemia and died. However, 90% of recipients receiving the purging treatment were healthy up to 9 months post-transplantation and had a perfectly re-established hematopoietic system, without any signal of leukemic cell presence. In conclusion, suicide adenoviral vectors are proposed as a tool for the purging of Adenoviral-susceptible myeloid leukemia cells contaminating autologous bone marrow grafts.

Linfocintigrafía para identificación de linfonodo centinela en cáncer de pene / Lymphoscintigraphy for centinel node identification in penile cancer

Se presenta un caso clínico de paciente con diagnóstico de cáncer de pene (T2 Nx M0) sometido a linfocintigrafía para identificación de linfonodo centinela. Se analiza el rol de este procedimiento como método de etapificación en esta patología y se revisa la historia y la experiencia de centros internacionales con este método diagnóstico.

Using animal data to improve prediction of human decompression risk following air-saturation dives.

To plan for any future rescue of personnel in a disabled and pressurized submarine, the US Navy needs a method for predicting risk of decompression sickness under possible scenarios for crew recovery. Such scenarios include direct ascent from compressed air exposures with risks too high for ethical human experiments. Animal data, however, with their extensive range of exposure pressures and incidence of decompression sickness, could improve prediction of high-risk human exposures. Hill equation dose-response models were fit, by using maximum likelihood, to 898 air-saturation, direct-ascent dives from humans, pigs, and rats, both individually and combined. Combining the species allowed estimation of one, more precise Hill equation exponent (steepness parameter), thus increasing the precision associated with human risk predictions. These predictions agreed more closely with the observed data at 2 ATA, compared with a current, more general, US Navy model, although the confidence limits of both models overlapped those of the data. However, the greatest benefit of adding animal data was observed after removal of the highest risk human exposures, requiring the models to extrapolate.

Elongation of the cytoplasmic domain, due to a point deletion at exon 7, results in an HLA-C null allele, Cw*0409 N.

The development of molecular techniques for HLA typing has allowed the identification of genes previously assigned as serologic blank alleles. Lack or poor cell surface expression has been found for molecules coded by HLA-A, -B, -DRB4, -DRB5, and -DPB1 genes. In this report we describe the first HLA-C gene encoding for a null cell surface molecule. HLA-Cw*0409 N shows a point deletion at position 1095 within exon 7. This mutation provokes a codon reading shift, generating a new translation stop codon 97 bp downstream to that described in alleles normally expressed. This new stop codon location implies the presence of 32 extra amino acid residues in the cytoplasmic domain. Transfection experiments suggest that elongation of the cytoplasmic domain in Cw*0409 N would be the cause of cell surface expression failure, although Cw*0409 N heavy chain is able to create stable complexes with beta2-microglobulin. HLA-C fragment length analysis in a small selected group of samples with B44-Cblk haplotypic associations allowed us to identify two additional subjects showing both a serologic silent Cw*04 allele and a point base deletion at the 3' end of the HLA-C gene. This finding indicates that the allele frequency of Cw*0409 N within serologic C blank alleles would be appreciable, although basically restricted to the (A23)-Cw*0409 N-B*4403-DR7-DQ2 haplotype.

Two new HLA class I alleles recognised by PCR sequence-specific primer and sequencing based typing: B*3805 and Cw*0408.

Two new HLA class I alleles have been recognised by molecular-based typing. B*3805 was initially identified by polymerase chain reaction using sequence-specific primers (PCR-SSP) and afterwards confirmed by sequencing based typing (SBT) studies in a Spanish Caucasian blood cord unit. A unique nucleotide change throughout exons 2, 3 and 4, leading to the amino acid replacement Ser11Ala, differentiates B*3801 and *3805. This position behaves as a dimorphic residue in HLA-B and -C loci, and seems to be structurally unrelated to peptide and TcR recognition. Cw*0408 was first detected by SBT in two African American bone marrow donors in combination with its most structurally related allele, Cw*04011. The single amino acid change found between Cw*04011 and Cw*0408 was Thr163Leu, a residue involved in pocket A of the peptide-binding cleft. This new allele could be the result of a gene conversion event between Cw*04011 and any of the Cw*03 alleles.

Selective transduction of murine myelomonocytic leukemia cells (WEHI-3B) with regular and RGD-adenoviral vectors.

On the basis of the susceptibility of normal myelomonocytic cells to adenoviral vectors, we have studied the possibility of selectively transducing myelomonocytic murine leukemic cells (WEHI-3B) with regular (Reg-Ad) and genetically modified (RGD-Ad) adenoviral vectors. An 8-h incubation of WEHI-3B cells with 100 pfu of Reg-Ad vectors/cell resulted in the whole population becoming positive for transgene expression. Under identical conditions of infection, 20-30% of mouse bone marrow (BM) cells were positive for the transgene. When RGD-Ad vectors were used, a brief exposure (10 min) of WEHI-3B cells to 150 pfu of the virus/cell was enough for 100% of the leukemia cells to become positive for the marker transgene (EGFP). Under these conditions, only 15-20% of BM cells and of primitive hematopoietic progenitors (Lin(-)Sca-1(+) cells) became EGFP(+), indicating an improved selectivity of the vectors for the leukemic cells. The incubation of WEHI-3B but not normal BM cells with soluble fiber protein (FP) inhibited the infection with Reg-Ad. The use of the RGD-Ad bypassed the FP-CAR interaction required for the transduction of WEHI-3B cells with Reg-Ad, suggesting that the abrogation of this requirement accounts for the improved infectivity of these leukemic cells and for the selectivity of RGD-Ad in targeting WEHI-3B leukemia cells.

Identification by sequencing based typing and complete coding region analysis of three new HLA class II alleles: DRB3*0210, DRB3*0211 and DQB1*0310.

The study of HLA class II polymorphism by direct exon 2 DNA sequencing analysis has been established to be a reliable and accurate high-resolution typing procedure. This approach shows some advantages in relation to previous methods, polymerase chain reaction using sequence-specific oligonucleotides (PCR-SSO) and sequence-specific primers (PCR-SSP), basically due to the capability of analysis for the complete sequenced genomic region, including non-polymorphic motifs. DRB3 and DQB1 sequencing based typing (SBT) in unrelated bone marrow donor searching allowed us to detect three new alleles. The complete coding region sequences were characterised from cDNA. Two new DRB3 alleles, DRB3*0210 and DRB3*0211, were described in two Caucasian bone marrow donors. Both sequences showed single point mutations regarding DRB3*0202, producing amino acid replacements at positions 51 (Asp to Thr) and 67 (Leu to Ile), respectively. These two point mutations can be found in other DRB alleles, and suggest that gene conversion would be involved in the origin of both alleles. A new DQB1 sequence was found in a Spanish patient that showed two nucleotide differences, positions 134 and 141, with regard to its close similar DQB1*03011 allele. Only substitution at position 134 provoked amino acid replacement at residue 45, Glu to Gly. This single amino acid change would be involved in the lack of serologic recognition of this new molecule by DQ7-specific reagents.

Mixed-gas model for predicting decompression sickness in rats.

A mixed-gas model for rats was developed to further explore the role of different gases in decompression and to provide a global model for possible future evaluation of its usefulness for human prediction. A Hill-equation dose-response model was fitted to over 5,000 rat dives by using the technique of maximum likelihood. These dives used various mixtures of He, N(2), Ar, and O(2) and had times at depth up to 2 h and varied decompression profiles. Results supported past findings, including 1) differences among the gases in decompression risk (He < N(2) < Ar) and exchange rate (He > Ar approximately N(2)), 2) significant decompression risk of O(2), and 3) increased risk of decompression sickness with heavier animals. New findings included asymmetrical gas exchange with gas washout often unexpectedly faster than uptake. Model success was demonstrated by the relatively small errors (and their random scatter) between model predictions and actual incidences. This mixed-gas model for prediction of decompression sickness in rats is the first such model for any animal species that covers such a broad range of gas mixtures and dive profiles.

[Treatment of hyperthyroidism with radioiodine: effects of administered dose on complications and thyroid function]. / Tratamiento del hipertiroidismo con radioyodo: efecto de la dosis administrada sobre la función tiroidea y complicaciones asociadas.

BACKGROUND: Radio-iodine is a definite therapy for Graves disease hyperthyroidism. However, the optimal dosage is still debatable. AIM: To assess the effects of different radioiodine doses on thyroid function and complications in patients with hyperthyroidism. MATERIAL AND METHODS: A retrospective analysis of 139 patients with hyperthyroidism, treated with ratio-iodine between 1988 and 1998. Radio iodine dose used was classified as low (< 10 mCi), intermediate (10-14.9 mCi) or high (> or = 15 mCi). RESULTS: Thirty-five patients were treated with low doses, 33 with intermediate doses and 71 with high doses. There were no differences between these patients in age, disease severity, frequency of post treatment euthyroidism or complications. Patients treated with low doses had a higher frequency of persistent hyperthyroidism than patients treated with high doses (25.7 and 4.2% respectively, p < 0.001). Likewise, the frequency of subsequent hypothyroidism was 60% in patients treated with low doses and 84.5% of those with high doses, in whom it also appeared earlier. Associated complications were clinically irrelevant. In seven patients, Graves ophthalmopathy progressed after treatment, but this progression was not associated with the dose used. CONCLUSIONS: Radio iodine in high doses is useful, safe and effective for the treatment of Graves hyperthyroidism.