Opinion survey on proposals for improving code stroke in Murcia Health District V, 2014. / Encuesta de opinión sobre propuestas de mejora del código ictus en el Área V de la Región de Murcia, 2014.

INTRODUCTION: Stroke is a time-dependent neurological disease. Health District V in the Murcia Health System has certain demographic and geographical characteristics that make it necessary to create specific improvement strategies to ensure proper functioning of code stroke (CS). The study objectives were to assess local professionals' opinions about code stroke activation and procedure, and to share these suggestions with the regional multidisciplinary group for code stroke. SUBJECTS AND METHOD: This cross-sectional and descriptive study used the Delphi technique to develop a questionnaire for doctors and nurses working at all care levels in Area V. An anonymous electronic survey was sent to 154 professionals. The analysis was performed using the SWOT method (Strengths, Weaknesses, Opportunities, and Threats). RESULTS: Researchers collected 51 questionnaires. The main proposals were providing training, promoting communication with the neurologist, overcoming physical distances, using diagnostic imaging tests, motivating professionals, and raising awareness in the general population. CONCLUSIONS: Most of the interventions proposed by the participants have been listed in published literature. These improvement proposals were forwarded to the Regional Code Stroke Improvement Group.

Unequal Impact of COL1A1 and COL1A2 Variants on Dentinogenesis Imperfecta.

Dentinogenesis imperfecta (DI) is the main orodental manifestation of osteogenesis imperfecta (OI) caused by COL1A1 or COL1A2 heterozygous pathogenic variants. Its prevalence varies according to the studied population. Here, we report the molecular analysis of 81 patients with OI followed at reference centers in Brazil and France presenting COL1A1 or COL1A2 variants. Patients were submitted to clinical and radiographic dental examinations to diagnose the presence of DI. In addition, a systematic literature search and a descriptive statistical analysis were performed to investigate OI/DI phenotype-genotype correlation in a worldwide sample. In our cohort, 50 patients had COL1A1 pathogenic variants, and 31 patients had COL1A2 variants. A total of 25 novel variants were identified. Overall, data from a total of 906 individuals with OI were assessed. Results show that DI was more frequent in severe and moderate OI cases. DI prevalence was also more often associated with COL1A2 (67.6%) than with COL1A1 variants (45.4%) because COL1A2 variants mainly lead to qualitative defects that predispose to DI more than quantitative defects. For the first time, 4 DI hotspots were identified. In addition, we showed that 1) glycine substitution by branched and charged amino acids in the α2(I) chain and 2) substitutions occurring in major ligand binding regions-MLRB2 in α1(I) and MLBR 3 in α2(I)-could significantly predict DI (P < 0.05). The accumulated variant data analysis in this study provides a further basis for increasing our comprehension to better predict the occurrence and severity of DI and appropriate OI patient management.

Nitric oxide production mediates oligogalacturonide-triggered immunity and resistance to Botrytis cinerea in Arabidopsis thaliana.

Nitric oxide (NO) regulates a wide range of plant processes from development to environmental adaptation. In this study, we investigated the production and/or function of NO in Arabidopsis thaliana leaf discs and plants elicited by oligogalacturonides (OGs) and challenged with Botrytis cinerea. We provided evidence that OGs triggered a fast and long lasting NO production which was Ca(2+) dependent and involved nitrate reductase (NR). Accordingly, OGs triggered an increase of both NR activity and transcript accumulation. NO production was also sensitive to the mammalian NO synthase inhibitor L-NAME. Intriguingly, we showed that L-NAME affected NO production by interfering with NR activity, thus questioning the mechanisms of how this compound impairs NO synthesis in plants. We further demonstrated that NO modulates RBOHD-mediated reactive oxygen species (ROS) production and participates in the regulation of OG-responsive genes such as anionic peroxidase (PER4) and a ß-1,3-glucanase. Mutant plants impaired in PER4 and ß-1,3-glucanase, as well as Col-0 plants treated with the NO scavenger cPTIO, were more susceptible to B. cinerea. Taken together, our investigation deciphers part of the mechanisms linking NO production, NO-induced effects and basal resistance to B. cinerea.

Pure duplication 21q21.2-->qter due to a rea(21) in a Down syndrome girl. Remarks on nomenclature.

We report on an 8-year-old girl with a typical Down syndrome phenotype and a 46,XX,rea(21)(qter-->p12::q21.2-->qter).ish rea(21)(qter-->pl2::q21.2-->qter)(LSI 21++,AML1++) karyotype; the mother had normal chromosomes but the father was unavailable. The great resemblance of the patient's rearranged chromosome to the rec(21)dup(q) from a parental pericentric inversion suggests that it would be better depicted as a recombinant-like chromosome. Altogether, 13 recombinant-like chromosomes of de novo or unknown (parents not karyotyped) origin have been described. Although these rearranged chromosomes should formally be described as derivatives because no parental inversion is identified, we underlie that the unofficial term recombinant-like would be more appropriate because no "multiple aberrations within a single chromosome" (as required by the ISCN) have been proved, not to mention that the term derivative usually designates abnormal chromosomes resulting from a translocation between non homologous chromosomes. Accordingly, we prefer to identify such rearrangements of a single chromosome precisely with the more neutral and sanctioned term rea (expanding its use to designate a rearranged chromosome) coupled with the lengthy description of the abnormal chromosome. We assume that the rea(21) chromosomes result from illegitimate recombination between non allelic homologous LCRs located in both the short and long arms.

Homophilic adhesion between Ig superfamily carcinoembryonic antigen molecules involves double reciprocal bonds.

Both carcinoembryonic antigen (CEA) and neural cell adhesion molecule (NCAM) belong to the immunoglobulin supergene family and have been demonstrated to function as homotypic Ca(++)-independent intercellular adhesion molecules. CEA and NCAM cannot associate heterotypically indicating that they have different binding specificities. To define the domains of CEA involved in homotypic interaction, hybrid cDNAs consisting of various domains from CEA and NCAM were constructed and were transfected into a CHO-derived cell line; stable transfectant clones showing cell surface expression of CEA/NCAM chimeric-proteins were assessed for their adhesive properties by homotypic and heterotypic aggregation assays. The results indicate that all five of the Ig(C)-like domains of NCAM are required for intercellular adhesion while the COOH-terminal domain containing the fibronectin-like repeats is dispensable. The results also show that adhesion mediated by CEA involves binding between the Ig(V)-like amino-terminal domain and one of the Ig(C)-like internal repeat domains: thus while transfectants expressing constructs containing either the N domain or the internal domains alone were incapable of homotypic adhesion, they formed heterotypic aggregates when mixed. Furthermore, peptides consisting of both the N domain and the third internal repeat domain of CEA blocked CEA-mediated cell aggregation, thus providing direct evidence for the involvement of the two domains in adhesion. We therefore propose a novel model for interactions between immunoglobulin supergene family members in which especially strong binding is effected by double reciprocal interactions between the V-like domains and C-like domains of antiparallel CEA molecules on apposing cell surfaces.

Sodium channel internalization in developing neurons.

Neurotoxin-induced activation of voltage-dependent Na+ channels provoked rapid (t1/2 = 15-20 min) channel down-regulation in cultured rat brain neurons, resulting in a 50%-70% decrease in [3H]saxitoxin and 125I-alpha-scorpion toxin binding capacities as well as a decrease in Na+ peak current. Experiments using 125I-alpha-scorpion toxin as both a Na+ channel activator and a surface channel probe showed that a fraction of the bound toxin was internalized, since it was not releasable by acidic washing. Internalization was inhibited by tetrodotoxin, abolished in Na(+)-free medium, and induced by amphotericin B, a Na+ ionophore. Moreover, down-regulation occurred only in immature neuronal tissue, either cultured fetal neurons or postnatal hippocampal slices, but was absent in adult brain. These observations indicate that Na+ channel internalization is triggered by Na+ influx into neurons and may be involved in the control of electrical activity during development.

Na(v)1.7 and Na(v)1.3 are the only tetrodotoxin-sensitive sodium channels expressed by the adult guinea pig enteric nervous system.

The types of sodium channels that are expressed by neurons shape the rising phase of action potentials and influence patterns of action potential discharge. With regard to the enteric nervous system (ENS), there is uncertainty about which channels are expressed, and in particular it is unknown whether Na(v)1.7 is present. We designed specific probes for the guinea pig Na(v)1.7 alpha subunit as well as for the other tetrodotoxin (TTX)-sensitive alpha subunits (Na(v)1.1, Na(v)1.2, Na(v)1.3, and Na(v)1.6) in order to perform in situ hybridization (ISH) histochemistry on guinea pig myenteric ganglia. We established that only Na(v)1.7 mRNA and Na(v)1.3 mRNA are expressed in these ganglia. The ISH signal for Na(v)1.7 transcripts was found in seemingly all the myenteric neurons. The expression of the Na(v)1.3 alpha subunit was confirmed by immunohistochemistry in a large proportion (62%) of the myenteric neuron population. This population included enteric sensory neurons. Na(v)1.6 immunoreactivity, absent from myenteric neurons, was detected in glial cells only when a high anti-Na(v)1.6 antibody concentration was used. This suggests that the Na(v)1.6 alpha subunit and mRNA are present only at low levels, which is consistent with the fact that no Na(v)1.6 mRNA could be detected in the ENS by ISH. The fact that adult myenteric neurons are endowed with only two TTX-sensitive alpha subunits, namely, Na(v)1.3 and Na(v)1.7, emphasizes the singularity of the ENS. Both these subunits, known to have slow-inactivation kinetics, are well adapted for generating action potentials from slow excitatory postsynaptic potentials, a mode of synaptic transmission that applies to all ENS neuron types.

False positive in the measurement of thyroglobulin induced by rheumatoid factor.

BACKGROUND: We report a case of interference in thyroglobulin (Tg) measurement in a woman with differentiated thyroid cancer and rheumatoid arthritis history. Due to discordant Tg in relation to TSH concentrations and negative images, we investigated possible interference in the measurement of Tg. METHODS: During the follow-up we measured Tg by chemiluminescence (TgQL) using Immulite 2000 immunoassay system. To investigate possible interference in Tg measurement, we made serial dilutions, re-testing of Tg by an alternative method: electrochemiluminescence, Cobas 6000 analyzer (TgEQL), recovery test of Tg and polyethylene glycol (PEG) 6000 precipitation. RESULTS: During the patient follow-up, the TgQL ranged between <0.3 and 16.1ng/ml. In the evaluated serum samples very high titers of rheumatoid factor (RF) were found. When RF titers were lowered post PEG precipitation, Tg QL concentrations became undetectable. CONCLUSION: We describe an unusual case of interference in Tg assay due to RF. When disagreement among Tg concentrations, images and clinical features is observed, we suggest taking into account the evaluation of possible Tg interference to avoid unnecessary complementary exams and inappropriate treatment.

Biosynthesis and processing of polysialylated NCAM by AtT-20 cells.

Polysialylation is a unique posttranslational modification of NCAM. In this report, we investigated the kinetics and localization of NCAM polysialylation in AtT-20 cells. We show that this cell line expresses both the 180 kDa and 140 kDa isoforms of NCAM, in agreement with the proposal that it belongs to a neuroendocrine lineage. The two NCAM chains bear polysialic acid (PSA) and migrate in sodium dodecyl sulfate (SDS) gels as a diffuse, high Mr component, as has been observed in fetal brain. Polysialylation of neosynthesized NCAM was found to be a rapid event, occurring within 8 to 13 min after the beginning of the pulse and appeared to be essentially complete as soon as it was detected. Treatment with endosialidase specific for PSA led to the appearance of two components of 200 and 160 kDa which still bear short sialosyl oligomers. Neither this treatment nor the slowing down of synthesis by lowering the temperature revealed any intermediate bearing oligomers of polysialic acid in the process of elongation suggesting the possibility that polysialylation may involve the transfer to NCAM of preassembled completed PSA chains. Endo H resistance preceded polysialylation, which was totally blocked by monensin and swainsonine which inhibit transport of plasma membrane or secreted proteins within the Golgi complex and the maturation of complex-type oligosaccharide chains, respectively. Depletion of cell-surface NCAM with proteinase K did not prevent the appearance of polysialylated molecules in similar amounts as in untreated cells suggesting that NCAM polysialylation occurs either in a late Golgi or in a post-Golgi compartment but before the molecules reach the plasma membrane.

The receptor for immunoglobulin E as a membrane protein.

Mast cells and related cells have a surface glycoprotein that avidly binds monomeric immunoglobulin E (IgE). This protein is more complex than originally thought, its analysis having been complicated by its lability in mild detergents. The properties of this receptor, especially with respect to its interaction with lipids and detergents, is reviewed and the implications for the study of other membrane protein systems are discussed.

Channel activators reduce the expression of sodium channel alpha-subunit mRNA in developing neurons.

The expression of rat brain sodium channel alpha-subunit (Na+I, Na+II and Na+III) and beta 1-subunit mRNAs was examined in rat fetal brain neurons in culture. A combined technique of reverse transcription and polymerase chain reaction (RT-PCR) was used. Two different PCR primer sets were designed to obtain simultaneous amplification of the three alpha-subunit mRNAs. All three molecules were detected in fetal neurons but the expression pattern (Na+III > Na+II > > Na+I) was different than that observed in adult tissue (Na+II > Na+I > Na+III). Expression of the beta 1-subunit mRNA was detected using a specific PCR primer set. Doublet bands were amplified, from fetal cells and adult brain mRNA. To get further insight into the molecular mechanism that underlie activity dependent plasticity of sodium channels, we studied the effect on the expression of sodium channel subunits mRNA of a 60 h incubation of cells in the presence of a scorpion neurotoxin that blocks channel inactivation. An overall decrease in the expression of all three alpha-subunit mRNAs was observed whereas the beta 1-subunit mRNA was unaffected by the same treatment. When cells were incubated with the scorpion neurotoxin together with tetrodotoxin, to block Na+ influx through channels, the decrease in mRNA expression was not observed. Finally, a 60 h continuous depolarization of cells induced by application of a high concentration KC1 solution did not mimic the effect of the scorpion toxin. These observations suggest that a persistent activation of the sodium channels is able to down-regulate mRNA expression for alpha-subunits but not for the beta 1-subunit.

Multiple pathways regulate the expression of genes encoding sodium channel subunits in developing neurons.

In primary cultures of fetal neurons, activation of sodium channels with either alpha-scorpion toxin or veratridine caused a rapid and persistent decrease of mRNAs encoding beta2 and different sodium channel alpha mRNAs. In contrast, beta1 subunit mRNA was up-regulated by sodium channel activation. This phenomenon was calcium-independent. The effects of activating toxins on mRNAs of different sodium channel subunits were mimicked by membrane depolarization. An important aspect of this study was the demonstration that cAMP also caused rapid reduction of alphaI, alphaII and alphaIII mRNA levels whereas beta1 subunit mRNA was up regulated and beta2 subunit mRNA was not affected. Sodium channel activation by veratridine was shown to increase cAMP immunoreactivity in cultured neurons, but alphaII mRNA down-regulation induced by activating toxins was not reversed by protein kinase A antagonists, indicating that this phenomenon is not protein kinase A dependent. The effects of cAMP and membrane depolarisation were antagonized by the PKA inhibitor H89. These results are indicative of the existence of multiple and independent regulatory pathways modulating the expression of sodium channel genes in the developing central nervous system.

Down-regulation of voltage-dependent sodium channels coincides with a low expression of alphabeta1 subunit complexes.

The association between the beta1 subunit and the alpha subunit of the sodium channel from rat brain was studied in hippocampus during postnatal development and in cultures of fetal rat forebrain neurons and cerebellar granule cells, using an anti-beta1 antipeptide antibody to specifically immunoprecipitate alphabeta1 complexes labeled with [3H]saxitoxin. In the hippocampus, the increase in beta1 RNA expression during development was accompanied by an increase in immunoprecipitated alphabeta1 complexes. Most of the alphabeta1 complexes were constituted during the first 3 postnatal weeks, with the steepest rise between postnatal days 5 and 12. In cultured fetal neurons, the amount of beta1 RNA and of alphabeta1 complexes was approximately 3-4% of that found in the adult, whereas it reached 60-70% in cultured cerebellar granule cells. We had previously described a neurotoxin-induced internalization of sodium channels which occurred in immature neurons but not in adult tissue. Internalization decreased during development in neurotoxin-treated hippocampal slices, and resistance of plasma membrane sodium channels to internalization followed the same time course than the appearance of alphabeta1 complexes. Similarly, neurotoxin activation resulted in sodium channel internalization in fetal neurons, while cerebellar granule cells, which express high levels of beta1 RNA and of alphabeta1 complexes, did not internalize their [3H]saxitoxin receptors in that same conditions. These data suggested that the association of the beta1 subunit with the alpha subunit could provide a suitable marker for the stabilization and anchoring of sodium channels in discrete membrane domains which occur during neuronal development.

Twenty-five years of experience in the surgical treatment of perforation of the ileum caused by Salmonella typhi at the General Hospital of Mexico City, Mexico.

BACKGROUND: This work summarizes the experience obtained during 25 years in the management of intestinal perforations caused by Salmonella typhi with a directed resection and anastomosis at the General Hospital of México City. METHODS: A total of 352 cases of perforation of the ileum caused by Salmonella typhi seen during the course of 25 years were studied. Patients were divided into two groups; group A had 236 patients and group B had 116 patients. All patients underwent either conventional resection and anastomosis or primary closure (group A) or directed intestinal resection of 10 cm at each side of the perforation on the basis of anatomopathologic studies with serial sections (group B). RESULTS: Morbidity and mortality for group B were each of 1.72%, significantly lower than the 33.47% morbidity and 7.20% mortality in group A. CONCLUSIONS: Primary closure should be discouraged, even for a single perforation. Instead directed intestinal resection is recommended as elective surgery for all cases of typhoid fever complicated with intestinal perforation, resecting 10 cm at each side of the distal and proximal perforation.

Overt and subclinical hypothyroidism complicating pregnancy.

We studied the evolution of 150 pregnancies corresponding to 114 women (16-39 years old) with primary hypothyroidism. Fifty-one pregnancies (34%) were conceived under hypothyroidism: 16 overt (X +/- standard deviation [SD], thyroxine [T4]: 2.44 +/- 0.7 microg/dL; thyrotropin [TSH]: 33.4 +/- 8.82 mIU/L), and 35 subclinical hypothyroidism (T4: 6.93 +/- 1.88 microg/dL; TSH: 12.87 +/- 8.43 mIU/L); 99 pregnancies were conceived under euthyroidism while undergoing thyroid therapy. When treatment with levothyroxine was inadequate, the outcome of pregnancy was abortion in 60% of overtly hypothyroid patients and in 71.4% of subclinically hypothyroid patients, premature delivery in 20% and 7.2% respectively, and term delivery in 20% and 21.4%, respectively. When treatment was adequate, 100% of overtly hypothyroid patients and 90.5% of subclinically hypothyroid patients carried pregnancies to term; there were no abortions in any of the groups. Abortions, premature and term deliveries in patients who were euthyroid on levothyroxine at the time of conception were 4%, 11.1% and 84.9% respectively. Of the patients receiving levothyroxine therapy before conception, 69.5% had to increase the dose (mean increase 46.2 +/- 29.6 microg/d). Of 126 evaluated newborns, 110 were delivered at term while 16 were premature. Eight newborns, 4 were premature, had congenital malformations (6.3%), and 4 died. Our results show that the evolution of pregnancies did not depend on whether the hypothyroidism was overt or subclinical but mainly on the treatment received. The adequate treatment of hypothyroidism during gestation minimizes risks and generally, makes it possible for pregnancies to be carried to term without complications.

Simulation of the clonal growth of Bostrychia radicans (Ceramiales-Rhodophyta) using Lindenmayer systems.

A mathematical model for the clonal growth of the alga Bostrychia radicans was constructed based on architectural growth rules and Lindenmayer systems. The sequence of theoretical growth and invasive strategy of space is shown in several graphical schemes which represent different steps of the model. We postulate that Bostrychia radicans has a 'phalanx' strategy of colonization (Lovett Doust, L. 1981. J. Ecol. 69, 743-755.) based on the biological interpretation of the model and field observations.

Endotelina-1, proteína C reactiva ultrasensible y actividad antioxidante en pacientes con hipotiroidismo subclínico y en eutiroideos con autoinmunidad tiroidea. Efectos del tratamiento con levotiroxina / Endothelin-1, high sensitivity C reactive protein and antioxidant activity in subclinical hypothyroid patients. Effects of levothyroxine treatment

RESUMEN La Endotelina-1 (ET1) y Proteína C Reactiva ultrasensible (PCRus) como marcadores de disfunción endotelial (DE) e inflamación vascular en hipotiroidismo subclínico (HS) han mostrado resultados controvertidos. El rol del estrés oxidativo y defensa antioxidante (TRAP) es motivo de discusión. Objetivos Establecer si el HS y la autoinmunidad tiroidea (AIT), excluyendo otros factores de riesgo cardiovascular, pueden causar DE e inflamación vascular, evaluadas a través de ET1 y PCRus, respectivamente. Establecer si TRAP juega algún rol. Evaluar cambios en ET1 y PCRus luego del tratamiento con levotiroxina (LT4). Material y métodos Se evaluaron prospectivamente 70 pacientes divididos en 3 grupos: HS: 41 pacientes (T4 normal,TSH >4,2 y <10 mUI/L), AIT: 10 pacientes eutiroideos (TSH <4,2 mUI/L) con aTPO y/o aTg (+) y Control: 19 pacientes eutiroideos sin AIT. Se excluyeron otros factores de riesgo cardiovascular. Se midió basalmente ET1, PCRus y TRAP plasmáticos, y en HS bajo LT4 (n = 24): ET1 y PCRus. Resultados No hubo diferencias significativas en edad, IMC, perfil lipídico y TRAP. ET1 y PCRus fueron significativamente mayores en pacientes con HS (media ± DS 1,77 ± 0,85 pg/ml y 1,5 ± 0,6 mg/l vs. controles (0,8 ± 0,3 pg/ml y 0,5 ± 0,2 mg/l) p <0,0001 y <0,008 respectivamente. Del mismo modo en AIT (1,4 ± 0.4 pg/ml y 2,3 ± 1,3 mg/l) vs controles p <0,0001 y <0,034, respectivamente. La TSH fue mayor en el grupo AIT vs. Control 2,57 ± 0,88 vs. 1,64 ± 0,5 mUI/L; p = 0,002. En HS bajo LT4 (8,7 ± 3,8 meses) se observó descenso de ET1 (p <0,001). ET1 correlacionó con TSH (r = 0,5 p <0,0001). El punto de corte de ET1 mediante curva ROC fue 1,32 pg/ml (Sensibilidad 81,6%-Especificidad 75%). Conclusiones ET1 y PCRus resultaron marcadores útiles para evaluar DE e inflamación vascular asociadas a HS. La defensa antioxidante no ejercería un rol en estos mecanismos. El tratamiento con LT4 produjo una significativa caída de ET1, pudiendo necesitarse un período más largo de eutiroidismo para normalizarla. En AIT, niveles de TSH >2,5 mUI/L podrían sugerir un mínimo grado de hipotiroidismo justificando la elevación en ET1 y PCR, sin descartar el rol de la AIT "per se".

ABSTRACT The measurement of endothelin-1 (ET1) and high sensitivity C-reactive protein (hsCRP) as markers of endothelial dysfunction (ED) and vascular inflammation in subclinical hypothyroidism (SH) has shown controversial results. The role of oxidative stress and antioxidant defense (TRAP) is a matter of discussion. Objectives To establish if SH and thyroid autoimmunity (TAI), excluding other cardiovascular risk factors, may cause ED and vascular inflammation, evaluated through the measurement of ET1 and hsCRP respectively. To determine if TRAP could have some role. Additionally, changes in these parameters after treatment with levothyroxine (LT4) will be evaluated. Material and methods: 70 patients were prospectively evaluated. They were classified into: SH Group: 41 patients (normal T4, TSH> 4.2 and <10 mIU/L), TAI Group: 10 euthyroid patients (TSH <4.2 mUI/L) with positive aTPO and/or aTg and Control Group: 19 euthyroid patients without TAI. Other cardiovascular risk factors were excluded in patients and controls. Plasma ET1, hsCRP and TRAP were measured basally, and ET1 and hsCRP under LT4 therapy in the HS Group. Results There were no significant differences between the 3 groups in age, BMI, lipids and TRAP. ET1 and hsCRP were significantly higher in patients with SH (mean ± SD 1.77 ± 0.85 pg/ml and 1.5 ± 0.6 mg/l) vs. controls (0.8 ± 0.3 pg/ml y 0.5 ± 0.2 mg/l) p <0.0001 y <0.008 respectively. Similarly, in TAI patients (1.4 ± 0.4 pg/ml y 2.3 ± 1.3 mg/l) vs controls, p <0.0001 and <0.034, respectively. TSH was higher in the TAI patients versus control group (2.5 ± 0.88 versus 1.64 ± 0.5 mIU/L, p = 0.002). Twenty-four patients with SH showed a significant decrease in ET1 (p <0.001) under treatment with LT4 (8.7 ± 3.8 months). ET1 had a highly significant correlation (p <0.0001) with TSH (r = 0.5). The cut-off level of ET1 established by ROC curve was 1.32 pg/ml (Sensitivity 81.6%-Specificity 75%). Conclusions ET1 and hsCRP were useful markers to evaluate ED and vascular inflammation associated with SH. There were no differences in TRAP levels between patients and controls, so it does not appear that oxidative stress would have played any role. Treatment with LT4 produced a significant drop in ET1. Probably, a longer period of euthyroidism might be necessary to normalize ET1 levels. In TAI Group, TSH levels >2.5 mUI/L could suggest a "minimal degree" of hypothyroidism justifying the elevation in ET1 and hs CRP. The role of the TAI "per se" couldn't be completely ruled out.

Carcinoma medular de tiroides: estudio multicéntrico. Presentación y evolución en 219 pacientes / Medullary Thyroid Carcinoma: Clinical Presentation and Outcome in 219 Patients

Ante la baja frecuencia del carcinoma medular de tiroides (CMT), en el Departamento de Tiroides de SAEM nos propusimos realizar un estudio de cohorte, observacional, retrospectivo y multicéntrico. Se incluyeron 219 pacientes con diagnóstico histológico de CMT. El 65 % fueron mujeres, la edad promedio fue de 39 ± 20 años (1 a 84 años); 44-% de los casos fueron familiares. Las formas de presentación más frecuentes fueron nódulo tiroideo (58 %) y pesquisa genética por antecedente familiar (22 %). Si bien la citología tiroidea fue diagnóstica de CMT en el 39 % de los casos, fue determinante de indicación quirúrgica en el 79 %. En el 47 % de los pacientes el diagnóstico de CMT se obtuvo previamente al tratamiento quirúrgico inicial por punción aspiración con aguja fina (PAAF), estudio genético o nivel de calcitonina (CT)). El 65 % se presentó en estadios avanzados (TNM III y IV). El estudio del protoncogen RET se realizó en 162 pacientes (74 %). En el 49 % se observó mutación siendo la más frecuente (76 %) en el codón 634. La forma hereditaria más frecuentemente observada fue el síndrome de neoplasia endocrina múltiple (NEM) 2A (57 % de los casos familiares), seguida por carcinoma medular familiar (25 %) y NEM 2B (13 %). Los casos familiares tuvieron menor edad al diagnóstico y mayor frecuencia de diagnóstico prequirúrgico. Los casos índice tuvieron mayor edad al momento del diagnóstico, mayores niveles de antígeno carcinoembrionario (CEA) y CT prequirúrgicos, mayor proporción de estadios III y IV y mayor porcentaje de evidencia de enfermedad al momento de la última consulta que aquellos detectados por pesquisa. En 143 pacientes (65 %) se obtuvieron registros completos de seguimiento en los que se analizaron los factores relacionados con la evolución. La mediana de seguimiento fue de 44 meses: fallecieron 21 pacientes (14,6 %) y 122 (86 %) viven; 76 de estos (54 %) se encuentran libres de enfermedad. El grupo con evidencia de enfermedad se presentó en estadios más avanzados. Resultaron factores de mayor riesgo para evidencia de enfermedad: sexo masculino, CMT esporádico, niveles elevados de CT prequirúrgicos, estadio IV y presencia de metástasis. Los niveles de CT posquirúrgicos fueron menores en aquellos pacientes que en la evolución final no presentaron evidencia de enfermedad. El principal factor pronóstico de la evolución de los pacientes con CMT fue el estadio de presentación, determinando la importancia del diagnóstico precoz con el fin de poder implementar un tratamiento quirúrgico curativo en estadios menos avanzados.

Due to the low frequency of medullary thyroid cancer (MTC), an observational, cohort, retrospective multicenter study was conducted at the Thyroid Department of the Endocrine and Metabolism Argentine Society (SAEM). We included 219 patients with histologically proven MTC, with a mean age of 39 ± 20 yr (range 1-84 years). Sixty five percent were women and 44% were familial cases. The most common presentations were thyroid nodule (58 %) and genetic screening due to family history (22 %). In 39 % of patients, diagnosis of MTC was made by fine needle aspiration, but cytology led to surgery in 79 %. In 47 % of patients, MTC was diagnosed by cytology, calcitonin (CT) levels or genetic studies prior to initial surgery. Sixty five percent of patients had advanced stages of the disease (TNM III or IV) at diagnosis. Proto-oncogene RET was studied in 162 patients (74 %). In 49% a mutation was reported, most frequently in codon 634 (76 %). Regarding hereditary forms of MTC, MEN 2A was the most frequent (57%), followed by familial MTC in 25 % and MEN 2B in 13 % of cases. Familial cases were younger subjects and had more frequently a pre-surgery diagnosis. Index cases were older, with higher CEA and CT levels, presented in more advanced stages and had more frequently evidence of disease at final assessment than patients who were diagnosed by genetic screening. Follow-up records of 143 patients were analyzed (65%); median time was 44 months; 21 patients died (14.6 %) and 122 survived (86 %), 76 showed no evidence of disease (NED) (54 %). High risk factors for evidence of disease at the final evaluation were: male gender, sporadic MTC, higher CT pre-surgery levels, stage IV and metastasis. Post surgery CT levels were lower in patients with NED. Stage at initial diagnosis was the main prognostic factor in patients with MTC, determining the importance of early detection for performing curative surgery in less advanced stages.

Programa nacional de bocio nodular (PRONBONO): Estudio multicéntrico de bocio nodular único palpable / National Program for Nodular Goiter (PRONBONO): Multicenter study of single palpable thyroid nodules

Introducción: La presencia de nódulos tiroideos palpables en la población general, es uno de los signos clínicos tiroideos más frecuentes en la práctica diaria. Objetivos: 1) establecer la prevalencia de las distintas patologías en bocio nodular único palpable y analizar sus características y su relación con los resultados citológicos. 2) analizar la existencia de diferencias regionales en Argentina. Pacientes y Métodos: Estudio prospectivo de 739 pacientes con bocio nodular único palpable evaluados entre el 1/1/2000 y el 31/12/2001 en Centros de Buenos Aires, Bahía Blanca, Mendoza y La Pampa. Se recabaron datos de examen clínico, ecografía tiroidea, TSH, ATPO y citología por punción con aguja fina. (PAAF). Fue utilizado para el análisis estadístico Correlación de Pearson, X2 y Test de Fisher. Resultados: la edad (X ± DS) fue 46,3 ± 14 años, 93,1 % eran de sexo femenino. El 1,6 % tenía historia de radiación en cuello y el 29,9 % antecedentes familiares de patología tiroidea. Hallazgos clínicos: disfagia en el 7,9 %, disfonía 3,5 %, crecimiento nodular en los últimos 6 meses 19,2 %, consistencia dura el 24,7 %, fijeza a estructuras adyacentes 1,5 % y adenopatías en el 3 %. Hallazgos bioquímicos: TSH normal en el 81,2 % y ATPO positivos en el 30,3 % de los casos. Características Ecográficas: nódulos sólidos: 53,1 %, hipoecoicos: 63,8 %, microcalcificaciones 10,3 %, halo incompleto: 15 %, multinodular: 30,5 %, tiroides heterogénea: 60,2 % y adenopatías: 3,8 %. Hallazgos citológicos: En el 86,8 % de los casos fue necesario solo una punción para llegar al diagnóstico. Insatisfactorio (excluyendo quiste): 3,2 %: benignos: 77,3 %; sospechosos: 12,6 % y cáncer: 7 % (42 papilar, 2 medular y 3 sin especificar). Una correlación significativa (p<0,02) fue observada entre citología maligna y crecimiento rápido, dureza, fijeza a estructuras vecinas, nódulo sólido, halo incompleto y adenopatías aunque estos parámetros son más frecuentes en números absolutos en nódulos benignos. La mayoría de las cirugías fueron indicadas en base al hallazgo citológico. El diagnóstico histológico de los 96 pacientes que fueron operados mostró 51 carcinomas, de los cuales solo dos tenían citología benigna y 31 adenomas. Conclusión: Los nódulos palpables únicos fueron más frecuentes en mujeres eutiroideas en la edad media de la vida. Un tercio tenía historia familiar de patología tiroidea, similar al porcentaje hallado de ATPO positivos. Por ecografía los nódulos fueron predominantemente sólidos, hipoecoicos, únicos con resto de la glándula tiroides heterogénea. La PAAF fue predominantemente benigna. El crecimiento rápido, la dureza, la fijeza a estructuras adyacentes, el halo incompleto y la presencia de adenopatías fueron relacionados con malignidad, pero la benignidad fue más frecuente. En la mayoría de los pacientes la cirugía fue recomendada por los hallazgos citológicos. Nuestros resultados son similares a los reportados en otras áreas geográficas.

Introduction: the presence of palpable thyroid nodules in the general population is one of the most common clinical signs of thyroid disease in daily practice. Objectives: 1) To assess the prevalence of pathologies, clinical and cytological findings of single palpable thyroid nodules (SPTN) in Argentina. 2) Analyze the regional differences in Argentina. Methods: Prospective study of 739 patients with STPN were evaluated at centres in Buenos Aires, Bahía Blanca, Mendoza, and La Pampa between 1/1/00 and 12/31/01. Clinical examination, thyroid ultrasound scan (US), TSH, TPOAb and fine needle aspirations (FNA) were performed. Statistics: Pearson Correlation, X2 & Fisher Tests. Results: Age (X ± SD) 46 ± 14ys: 93.1 % were women. Previous history of neck radiation & familial thyroid disease were found in 1.6 and 29.9 % respectively. Clinical findings: dysphagia: 7.9 %; dysphonia: 3.5%; nodule growth: 19.2 %; hard consistence: 24.7 %; fixation to adjacent structure: 1.5 % and lymphadenopathies (ADP): 3 %. Biochemical findings: TSH was normal in 81.2 % & TPOAb+ in 30.3 %. US features: solid: 53.1 %; hypoechoic: 63.8 %; microcalcifications: 10.3 %; incomplete halo: 15 %; more than 1 nodule: 30.5 %; thyroid heterogeneity: 60.2 % and ADP: 3.8 %. Cytology: Only 1 FNA was needed in 86.8%. Unsatisfactory (excluding cysts): 3.2 %; benign: 77.2%; suspicious: 12.6 % and cancer: 7 % (42 papillary, 2 medullary and 3 non specified). A significant correlation (p<0.02) was established between malignant nodules and rapid growth, hard, fixed, solid nodule, incomplete halo and ADP, though these parameters were more frequent (in absolute number) in benign nodules. Surgery was mainly indicated based on FNA results. Histological diagnosis of 96 patients who underwent surgery showed 51 carcinomas, of which only 2 were cytologically benign and 31 adenomas. Conclusion: Palpable single nodules were more frequent in middle aged euthyroid women. One third had familial thyroid pathology, similar to the presence of TPOAb. On US, nodules were predominantly solid, hypoechoic, single with heterogeneous thyroid gland. FNA was predominantly benign. Rapid growth, hard, fixed, solid nodule, incomplete halo and ADP were associated with malignancy, but benignity was more common. In most of the patients surgery was recommended based on cytological findings. Our results are similar to those reported in other geographic areas.