Etiología y evolución de recién nacidos con hipotiroidismo congénito y glándula eutópica / Etiology and evolution of newborns with congenital hypothyroidism and eutopic thyroid gland

RESUMEN Objetivos Analizar las características clínicas, bioquímicas, estudios complementarios, hallazgos moleculares y la prevalencia de glándula eutópica en neonatos con HC pertenecientes al Programa Provincial de Pesquisa Neonatal de Córdoba, Argentina, entre 1996 y 2015. Analizar la evolución de los pacientes que reunieron criterios para una reevaluación. Pacientes y métodos Se analizaron retrospectivamente las historias clínicas de 237 pacientes detectados por pesquisa neonatal en la provincia de Córdoba, Argentina, entre 1996-2015 con una incidencia promedio de 1/2146 pesquisados. Presentaron glándula eutópica 81 pacientes (34%) F35/M46; se excluyeron 10 con síndromes genéticos asociados. Se analizaron los niveles de: TSH, T4T, T4L, T3, TPOAb / TGAb y Tiroglobulina (ECLIA -ROCHE) (VR: >15 días: 6-83 ng/ ml; <15 días: 29-173 ng/ml), ecografía y centellografía de cuello con Tc-99m. El valor de corte de TSH sérica adoptado para la confirmación diagnóstica fue de ≥10 mUI/ml. Se realizaron estudios de biología molecular en casos seleccionados. Se reevaluaron niños mayores de 3 años, sin bocio, con valores normales de Tiroglobulina y sin requerimiento de incrementos en la dosis de LT4. Resultados: La prevalencia de HC y Tiroides Eutópica se mantuvo constante. El 50% de los pacientes (36/71) mostraron hiperplasia glandular tiroidea. El 84% (n: 60 de 71) presentó niveles de TSH sérica ≥20 uUI/ml (20-1186) y el 75% (n: 53 de 71) >40 uUI/ml (40-1186). TGAb and TPOAb fueron positivos en un niño. La determinación de TG fue normal en el 29% (21/71) de los casos, elevada en el 56% (39/71) y baja en el 14% (10/71). Los estudios de biología molecular resultaron diagnósticos en 26 pacientes de 18 familias, demostrándose mutaciones en los genes de: TPO: 9 pacientes, TG: 12 pacientes, NIS: 2 pacientes, DUOX2: 2 pacientes y TRβ: 1 paciente. Se encontraron 11 nuevas mutaciones: tres en TPO, cinco en TG, dos en NIS y una en DUOX2. Se informaron anomalías congénitas en el 11% (8/71) de los pacientes. Se reevaluó el 11% (8/71) de los niños, resultando: HC transitorio n: 5, permanente n: 2 y una niña con Síndrome de Resistencia a las Hormonas Tiroideas. La prevalencia de lactantes con HC y glándula eutópica se mantuvo constante a lo largo de 19 años del Programa. Conclusiones Nuestros estudios demuestran que la prevalencia de Hipotiroidismo Congénito con glándula eutópica se mantuvo estable en los períodos analizados. Este grupo de pacientes se caracterizó predominantemente por presentar HC de carácter permanente acompañado por fenotipos de moderada a severa intensidad. En el futuro deberá profundizarse el conocimiento respecto a la influencia de factores medioambientales, como posibles agentes de riesgo asociados a la génesis de Hipotiroidismo Congénito.

abstract Objectives To describe clinical, biochemical characteristics and complementary studies to diagnosis, molecular findings and the prevalence of eutopic gland in newborn with CH detected through our neonatal screening program in Córdoba, Argentina, between 1996 and 2015. To analyze the evolution of the patients who met criteria for re-evaluation. Patients and methods We retrospectively analysed medical records of 237 patients with CH detected by neonatal screening in Córdoba, Argentina, from 1996 to 2015 with an average incidence of 1/2146 researched. 81 patients (34%) F35/M46 had eutopic thyroid gland; 10 patients with associated genetic syndromes were excluded. TT4, FT4, T3, TSH, TPOAb, TGAb and Thyroglobulin (VR: >15 days: 6-83 ng/ml; <15 days: 29-173 ng/ml) (ECLIA ROCHE), thyroid ultrasonography and 99Tc scan were assessed. The serum TSH cutoff value adopted for diagnostic confirmation was ≥10 mIU/ml. Molecular biology studies were performed in selected cases. Those who had no goiter, with normal thyroglobulin, and had not required increases in L-T4 dose underwent re-evaluation after the age of 3 years. Results The prevalence of HC and thyroid Eutopic remained constant. 50% of the patients (36/71) showed glandular hyperplasia. In 84% (60/71) presented serum TSH levels ≥20 uUI/ml (20-1186) and in 75% (n: 53 of 71) levels >40 uUI/ml (40-1186). TGAb and TPOAb were positive only in one baby. TG levels were: normal in 29% (21/71) of the cases, elevated in 56% (39/71) and low in 14% (10/71). Gene mutations were found in 26 patients from 18 families: TPO: 9 patients, TG: 12 patients, NIS: 2 patients, DUOX2: 2 patients y TRβ: 1 patient. Eleven new mutations were found: three in TPO, five in TG, two in NIS and one in DUOX2. Congenital anomalies were reported in 11% (8/71) patients. The 11% (8/71) of children were re-evaluated resulting in: 5 Transient CH, 2 Permanent CH and 1 with Resistance to Thyroid Hormones. The prevalence of infants with CH and eutopic gland remained constant along 19 years of the Program. Conclusions Our studies show that the prevalence of congenital hypothyroidism with eutopic gland remained stable in the periods analyzed. This group of patients was predominantly characterized by permanent CH accompanied by moderate to severe phenotypes. In the future, knowledge about the influence of environmental factors, as possible risk agents associated with the genesis of Congenital Hypothyroidism, should be deepened.

Activated Regulatory T Cells Expressing CD4(+)CD25(high)CD45RO(+)CD62L(+) Biomarkers Could Be a Risk Factor in Liver Allograft Rejection.

Activated regulatory T cells (aTregs) are nowadays a hot topic in organ transplantation to establish their role during acute rejection (AR) episodes. The aim of this multi-center study was to monitor the frequency of aTregs within the first year after transplantation in a cohort of first-time liver transplant recipients enrolled from 2010 to 2012. aTregs frequency was analyzed by means of flow cytometry. Patients who had AR showed higher levels of aTregs during first year after transplantation in comparison with patients who did not have higher levels. High levels of aTregs in liver recipients might be used as a biomarker of AR; however, further studies must be done to address the potential role of aTregs as biomarkers of AR in liver transplantation.

Pro- and anti-inflammatory cytokine gene single-nucleotide polymorphisms in inflammatory bowel disease.

Anti-inflammatory cytokines have an important role in disease, tumour and transplant processes. Alterations in the regulation of several cytokines have been implicated in a variety of inflammatory disorders, including IBD (inflammatory bowel disease) [Crohn's disease (CD) and ulcerative colitis (UC)]. Cytokine polymorphisms are also known to affect the level of gene expression. Thus, the aim of this study was to determine the relationship between cytokine polymorphisms and the IBD pathologies in a Spanish population. Polymorphisms analysis was performed using PCR-SSOP using a microbeads luminex assay. The following polymorphisms were determined: TNFα [-238G/A (rs361525) and -308G/A (rs1800629)], IFNγ [+874A/T (rs62559044)], TGFß [+869C/T (rs1982073) and +915G/C (rs1800471)], IL10 [-1082A/A (rs1800896), -592A/C (rs1800872), -819C/T (rs1800871)], IL6 [-174C/G (rs1800795)], IL12p40 [3'UTR -1188A/C (rs3212227)], IL1α [-889C/T (rs1800587)], IL1ß [-511C/T (rs1143634) and +3962C/T (rs1143633)], IL1R [Pst-1 1970C/T] and IL1RA [Mspa-1 11100C/T]. No statistical differences in TNFα, IFNγ, TGFß, IL10, IL6, IL1α, IL1ß, IL1R and IL1Ra genotypes and allele distributions between the IBD groups and healthy controls were found. However, we observed significant differences in the 3'UTR -1188A/C polymorphism of IL12p40. So -1188A allele was increased in patients with UC and the -1188C allele (high IL12p40 production) was increased in patients with CD with respect to controls. These data are in concordance with the fact that CD has been shown to be associated with a Th1 T-cell-mediated inflammation model and high IL12/IFNγ production at histological affected sites. These data suggest that cytokine polymorphisms in TNFα, IFNγ, TGFß, IL10, IL6 and IL1α, IL1ß, IL1R and IL1Ra cytokine gene do not seem to be relevant in IBD susceptibility and IL12p40 3'UTR -1188A/C polymorphism seems to be associated with a differential IBD development.

Early experience with customized, meal-triggered gastric electrical stimulation in obese patients.

BACKGROUND: We report our initial gastric electrical stimulation experience using the abiliti® system for the treatment of obese patients followed for 1 year. METHOD: Between March 2011 and June 2013, 27 obese patients (BMI 30 to 46 kg/m(2)) were enrolled in a prospective open label study and implanted with a gastric stimulator. The patients were provided with nutritional support, and sensor-based behavioral feedback. RESULTS: At 12 months, percent excess weight loss (%EWL) obtained was 49.3 ± 19.2 % with no significant differences between gender or age sub-groups. The %EWL data were segmented into two groups according to BMI 30-40 kg/m(2) patients (obesity grade I and II) and BMI >40 kg/m(2), with the results of weight loss being significantly higher for the lower BMI group (59.1 ± 19.5 vs. 46.7 ± 13.4, respectively, p < 0.01). One subject requested to have his device explanted, and the minor postoperative adverse events were resolved without hospital admission. All patients experienced early satiety and reduced their intake. CONCLUSIONS: After 12 months of follow-up, gastric electrical stimulation treatment appears to be a safe and effective option for weight loss in obese subjects. Long-term follow-up and further studies are warranted.

Genetic polymorphisms of tumour necrosis factor alpha (TNF-α) promoter gene and response to TNF-α inhibitors in Spanish patients with inflammatory bowel disease.

Tumour necrosis factor alpha (TNF-α) has an important role in inflammatory response. Alterations in the regulation of TNF-α have been implicated in a variety of inflammatory disorders, including Inflammatory bowel disease (IBD). Indeed, a common treatment for IBD is the use of TNF-α inhibitors. Polymorphisms in the TNF-α promoter region are known to affect the level of gene expression. Our aim was to investigate the influence of these single nucleotide polymorphisms (SNPs) in TNF-α promoter gene play in the risk of IBD in a Spanish population and their individual response to anti-TNF-α treatment. DNA samples from patients with IBD and controls were screened for TNF-α -238G/A (rs361525) and -308G/A (rs1800629) SNPs by PCR-SSOP using a microbeads luminex assay and compared with response to TNF-α inhibitors. There were not statistical differences in -238G/A and -308G/A allele and genotype frequencies between patients. However, we found an increased frequency of -308A allele and -308GA genotype in these nonresponders patients to TNF-α inhibitors with respect to responders patients (Pc < 0.05). This -308GA genotype has been classified as high producer of this cytokine. This fact could actually be interesting to explain the different response of patients with IBD with respect to TNF-α inhibitors. TNF-α promoter gene polymorphism does not seem to play a role in IBD susceptibility, but particular TNF-α genotypes may be involved in the different responses to TNF-α inhibitor treatment in Spanish patients with IBD.

Patients with terminal chronic liver pathology faced with this disease.

BACKGROUND: "Anxious preoccupation" is a maladaptive coping strategy for patients with terminal chronic liver pathology causing psychopathologic emotional responses. The aim of this study was to identify "anxious preoccupation" as a coping strategy when faced with this disease and to investigate its relationship with emotional-type psychopathologic symptoms in patients awaiting a liver transplant (LT). METHODS: A total of 63 patients awaiting an LT were evaluated. The instrument used to evaluate coping style was the Mental Adjustment to Cancer questionnaire. One of the coping scales of this questionnaire is "anxious preoccupation" (9 items). An Instrument for psychopathologic assessment was used, the SA-45 questionnaire, which assessed 9 psychopathologic dimensions: somatizations, obsessions-compulsions, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism. RESULTS: "Anxious preoccupation" was used as an inadequate coping style by 51% of patients when faced with the disease. Five psychopathologic dimensions were associated with this coping strategy: 1) obsessive-compulsivity: 75% of patients with "anxious preoccupation" had obsessive-compulsivity symptoms compared with 29% of patients with other coping strategies (P < .001); 2) interpersonal sensitivity: 25% vs 6%, respectively (P = .044); 3) depression: 59% vs 29% (P = .015); 4) anxiety: 75% vs 32% (P = .001); and 5) phobic anxiety: 19% vs 3% (P = .050). CONCLUSIONS: More than one-half of the patients on the LT waiting list used "anxious preoccupation" as a coping style for this disease. This strategy was associated with a greater presence of emotional-type psychopathologic symptoms in these patients.

Microbial communities adhering to the obverse and reverse sides of an oil painting on canvas: identification and evaluation of their biodegradative potential.

In this study, we investigated and compared the microbial communities adhering to the obverse and the reverse sides of an oil painting on canvas exhibiting signs of biodeterioration. Samples showing no visible damage were investigated as controls. Air samples were also analysed, in order to investigate the presence of airborne microorganisms suspended in the indoor atmosphere. The diversity of the cultivable microorganisms adhering to the surface was analysed by molecular techniques, such as RAPD analysis and gene sequencing. DGGE fingerprints derived from DNA directly extracted from canvas material in combination with clone libraries and sequencing were used to evaluate the non-cultivable fraction of the microbial communities associated with the material. By using culture-dependent methods, most of the bacterial strains were found to be common airborne, spore-forming microorganisms and belonged to the phyla Actinobacteria and Firmicutes, whereas culture-independent techniques identified sequenced clones affiliated with members of the phyla Actinobacteria and Proteobacteria. The diversity of fungi was shown to be much lower than that observed for bacteria, and only species of Penicillium spp. could be detected by cultivation techniques. The selected strategy revealed a higher microbial diversity on the obverse than on the reverse side of the painting and the near absence of actively growing microorganisms on areas showing no visible damage. Furthermore, enzymatic activity tests revealed that the most widespread activities involved in biodeterioration were esterase and esterase lipase among the isolated bacterial strains, and esterase and N-acetyl-ß-glucosaminidase among fungi strains.

Laparoscopic treatment of biliary peritonitis after removal of T-tube in liver transplant patients.

INTRODUCTION: T-tube removal in liver transplant patients can occasionally cause a massive biliary leak and may require surgical treatment for its resolution. We present our experience with a laparoscopic approach to biliary peritonitis in liver transplant patients after the removal of a T-tube. PATIENTS AND METHODS: From January 2003 until February 2010, we performed 351 liver transplantations in 313 recipients, including 135 with a T-tube. After its removal 31 biliary leaks developed (23%); 12 were massive and required surgery, which utilized a laparoscopic approach. RESULTS: The mean length of the intervention was 72.9 ± 12.87 minutes (range = 55-95), without any complications during the procedure, and no need to convert to a laparotomy. Mean hospital stay after the intervention was 6.75 ± 3.88 days (range 4-18). There was no mortality from the procedure. CONCLUSION: The laparoscopic approach for biliary leakage after T-tube removal is indicated when large diffuse acute peritonitis is established a few hours postremoval of the T-tube. This safe procedure treats the complication without the need for another laparotomy.

Evolution of soluble forms of CD86, CD95 and CD95L molecules in liver transplant recipients.

Co-stimulatory factors such as CD86 and apoptotic molecules such as CD95 and CD95L required to start and to turn off the allogenic immune response may also be present as soluble proteins. To determine the role of the soluble forms of CD86 (sCD86), CD95 (sCD95) and CD95L (sCD95L) in the outcome of liver transplants, we analyzed the circulating levels of these molecules in patients subjected to liver transplantation in the pre-operative period and during the first month post-transplantation. Serum samples were obtained from sixty-nine first orthotopic liver transplants (OLT). The patients were classified into acute rejection (AR=24) and not acute rejection (NAR=45), or considering the presence of chronic active hepatitis B or C (VP=30) or other primary liver diseases (VN=39). The levels of sCD86, sCD95 and sCD95L were analyzed by solid phase sandwich enzyme-linked immunoabsorbent assays. Our results first showed that the pre-transplantation serum levels of sCD86 in the AR group were significantly higher than in the NAR group (1007±82U/mL vs. 739±46U/mL, p=0.006), and in the post-transplantation period these levels decreased sharply. Second, the levels of sCD95L and sCD95 in the pre-transplantation period did not point to statistically significant differences between the AR and NAR groups. Considering primary liver disease, the pre-transplantation levels of sCD86 and sCD95L in the VP group were significantly higher than those of the VN group (VP, 977±69U/mL vs. VN, 722±51U/mL, p<0.002, and VP, 482±78pg/mL vs. VN, 221±31pg/mL, p=0.002, respectively). Multivariate analysis revealed that only the pre-transplantation levels of sCD86 were independently associated with the development of episodes of acute rejection (p=0.005, OR=2.1, IC 95%=1.27-3.47). In conclusion, the present work shows that primary liver disease could influence the pre-transplantation levels of sCD86 and sCD95L. High pre-transplantation serum levels of sCD86 could favor the development of episodes of acute rejection.

Value of 18-FDG-positron emission tomography/computed tomography before and after transarterial chemoembolization in patients with hepatocellular carcinoma undergoing liver transplantation: initial results.

INTRODUCTION: Liver transplantation is the treatment of choice for various types of end-stage liver disease and the most appropriate alternative for the treatment of hepatocellular carcinoma (HCC)-associated liver cirrhosis. The aim of this study was to describe our initial experience with the use of 18-FDG positron emission tomography (PET)/computed tomography CT before and after transarterial chemoembolization (TACE) in HCC patients undergoing liver transplantation, seeking to predict the percentage of tumor necrosis achieved by TACE procedures. PATIENTS AND METHODS: From January 2007 through December 2009, 39 patients with HCC and liver cirrhosis were included in our liver transplantation program. We selected the 6 subjects who underwent 18-fluorodeoxyglucose PET/CT (18-FDG PET/CT) pre- and post-TACE. RESULTS: The median SUV (standardized uptake value) in the lesions studied were 4 (range, 2.79-6.95) before TACE with a median post-TACE SUV of 0 (range, 0-4). Among patients whose post-TACE SUV decreased to <3, the percentage of necrosis after studying the hepatectomy was >80%. CONCLUSION: Performance of an 18-FDG PET/CT before and after TACE and comparison of SUV in patients with HCC awaiting liver transplantation provided valuable information regarding the effectiveness of TACE.

Transhepatic portal venous angioplasty with stenting for bleeding jejunal angiodysplasias in a retrasplant patient: a case report.

A 41-year-old man, who had undergone liver retransplantation, was admitted to our institution complaining of rectorraghia. Gastroscopy and colonoscopy failed to detect the source of bleeding. Computed tomographic angiography detected a stenosis at the portal anastomosis. Capsule endoscopy showed the presence of multiple small bowel angiodysplasias. After a surgical failure, direct portography revealed severe stenosis of the extrahepatic portal vein. Subsequent to percutaneous transhepatic portography, we dilated the stenosis using a balloon catheter and placed an expandable metallic stent, stopping the bleeding without further episodes of gastrointestinal bleeding.

Nanocomposite synthesis by absorption of nanoparticles into macroporous hydrogels. Building a chemomechanical actuator driven by electromagnetic radiation.

Macroporous hydrogels irreversibly absorb solid nanoparticles from aqueous dispersions. A nanocomposite is made using a macroporous thermosensitive hydrogel (poly(N-isopropylacrylamide-co-(2-acrylamido-2-methyl propane sulfonic acid)) (poly(NIPAm-co-AMPS)) and conductive polymer (polyaniline, PANI) nanoparticles (PANI NPs). Macroporous gels of poly(NIPAm-co-AMPS) were made by a cryogelation technique. NPs of PANI were produced by precipitation polymerization. It is found that PANI NPs are easily absorbed into the macroporous hydrogels while conventional non-porous hydrogels do not incorporate NPs. It is shown that PANI NPs, dispersed in water, absorb NIR laser light or microwave radiation, increasing their temperature. Upon irradiation of the nanocomposite with microwaves or NIR laser light, the PANI NPs heat up and induce the phase transition of the thermosensitive hydrogel matrix and the internal solution is released. Other nano-objects, such as gold nanorods and PANI nanofibers, are also easily incorporated into the macroporous gel. The resulting nanocomposites also suffer a phase transition upon irradiation with electromagnetic waves. The results suggest that, using a thermosensitive matrix and conducting nanoparticles, mechanical/chemical actuators driven at a distance by electromagnetic radiation can be built. The sensitivity of the nanocomposite to electromagnetic radiation can be modulated by the pH, depending on the nature of the incorporated nanoparticles. Additionally, it is possible to make systems which absorb either NIR or microwaves or both.

Coping styles of patients on the liver transplant waiting list.

INTRODUCTION: Chronic end-stage liver disease is a difficult situation for the patient. OBJECTIVE: The objective of this study was to analyze the disease coping styles of patients on the liver transplant waiting list. MATERIALS AND METHODS: The study included 50 patients on the liver transplant waiting list. The instrument used was the Mental Adjustment to Cancer Scale (Ferrero, 94). Coping scales were as follows: fighting spirit, hopelessness, anxious preoccupation, fatalism, and negation. RESULTS: Only 6% of subjects adapted well, whereas 94% adapted badly: 89% poor fighting spirit, 32% hopelessness, 50% anxious preoccupation, 28% fatalism, and 30% negation. Of those who had a poor fighting spirit, 88% also used another type of maladaptive style. The associated statements were (P<.05) as follows: "I value my life more"; "I don't think about the disease"; "I think about people who are worse off." Regarding hopelessness, 100% of those who confessed hopelessness also showed maladaptive signs. The associated statements were (P<.05) as follows: "I cannot cheer myself up"; "I cannot help myself"; "I've given up." Regarding anxious preoccupation, nearly all of these patients (96%) provided dysfunctional answers. The most associated were (P<.05) as follows: "I don't have any plans"; "I feel a lot of anxiety"; "I'm very angry." Regarding fatalism, all of the patients also had maladaptive behavior. The main types were (P<.05) as follows: "Nothing will change things"; "I cannot control the situation"; "I don't need information." Regarding negation, Only 14% used this style, and in 86% negation was associated with other inadequate coping styles. CONCLUSIONS: Patients on the liver transplant waiting list were maladaptive to their disease. It is important to establish adequate psychological care for these patients, given the important repercussions in the posttransplantation phase.

Improving the waiting list by using 75-year-old donors for recipients with hepatocellular carcinoma.

The best treatment for hepatocellular carcinoma (HCC) associated with liver cirrhosis is liver transplantation and the best results are obtained when the tumors fulfill the Milan criteria. However, although the number of transplants is increasing, the organ deficit is growing, which lengthens time on the waiting list, increasing the risk of tumor progression of and exclusion from the list. The use of elderly donors is a valid option for patients on the transplant waiting list with HCC, reducing time on the waiting list. We report our experience with patients transplanted for HCC associated with hepatic cirrhosis using livers from donors >75 years of age. Our preliminary results supported the use of elderly suboptimal donors making it possible to give priority to these patients. All patients in the series achieved good graft function after a follow-up of 2 years with a 100% disease-free survival rate. More extensive long-term studies are needed to confirm these findings.

[Intragastric balloon in obesity treatment]. / Balón intragástrico en el tratamiento de la obesidad.

Obesity is considered a chronic and epidemic illness, hece difficult to treat. As conservative treatment has a high rate of failure, and considering morbimortality and sequels of surgery, less invasive techniques appeared to contribute to the treatment of this illness. The most implanted technique nowadays is the Intragastric Balloon, considered more efficient as conservative treatments and with less risks tan surgery, but having today a lack of consensus on indications and few information on his limitations, while its apparition in medias promote an important expansion in the 4 last years. In this publication, we do a critical revision, and describe limitations of this treatment, based on the evidences given by literature. We conclude this revision with some recommendations concerning the technique and indications, material and human requiring, need of a Multidisciplinary Team, as well as an adequate control and following.

Role of liver transplantation in the management of unresectable neuroendocrine liver metastases.

UNLABELLED: The use of OLT in the management of liver metastases of any origin is highly controversial, as most patients receiving a transplant for this indication display poor results owing to early tumor spread secondary to the effects of immunosuppression. However, as they have a better biological behavior, neuroendocrine (NE) tumors may be a good indication for OLT. Our aim was to present our experience in the management of unresectable liver metastases of tumors of NE origin. PATIENTS AND METHODS: Between January 1996 and April 2006, 10 patients underwent OLT for unresectable liver metastases of a neuroendocrine origin, accounting for 1.2% of all transplants performed to date in our unit (n = 626). The most common location of the primary tumor was the pancreas in six cases: three in the pancreatic tail--one carcinoid tumor, one gastrinoma, and one nonfunctioning NE [NF-NE] tumor; and three cases in the pancreatic head--three NF-NE tumors. In the remaining four cases, including three carcinoid tumours and one NF-NE tumors, two were located in the small bowel (at the ileum and ileocecal valve) and two in the lung. The liver metastases were synchronous with the primary tumor in seven cases and metachronous in three cases. RESULTS: The morbidity rate was 75% and the mortality rate, 10% (n = 1). The tumor recurrence rate was 33% with 1- and 3-year survival rates of 86% and 57%, respectively.

Clinical evolution in the first 3 months of patients after liver transplantation in maintenance phase converted from mycophenolate mofetil to mycophenolate sodium due to gastrointestinal complications.

The enteric-coated mycophenolate sodium (EC-MPS) is a new formulation of mycophenolic acid with a gastro-resistant enteric coating, which releases the drug in the intestine, reducing the incidence of the gastrointestinal (GI) adverse effects. The present work provided a summary of 20 patients with liver transplantation and more than a 1 year of treatment with mycophenolate mofetil (MMF) who, after presentation of GI complications, were converted to EC-MPS. The patients were followed over a 3-month period after beginning EC-MPS treatment. The mean age of the cohort was 53 +/- 10 years and included 75% men. The reasons for transplantation were ethanol cirrhosis (70%), hepatitis C cirrhosis (30%), hepatocarcinoma (5%), and Wilson's disease (5%). At baseline, all patients were being treated with cyclosporine (CsA). CsA doses and levels were reduced during follow-up: baseline dose 179 mg/day versus 143 mg/day at 3 months; levels: 90.4 ng/mL versus 85.8 ng/mL, respectively (P = .017). The administered dose of EC-MPS was 720 mg/day in all cases. The GI complications at baseline were: diarrhea 60% (92% moderate-severe), abdominal discomfort 60% (58% moderate), abdominal pain 45% (44% moderate-severe), gas 40% (38% moderate-severe), nausea 20% (25% moderate), and dyspepsia 20% (mild). After 3 months of EC-MPS treatment, only two patients (10%) displayed moderate diarrhea. The renal evolution was favorable, serum creatinine was reduced, and 24-hour creatinine clearance significantly increased (creatinine: 1.78 +/- 1.6 mg/dL at baseline versus 1.30 +/- 0.3 mg/dL at 3 months, P = .002; creatinine clearance: 72.8 +/- 18 mL/min versus 79.6 +/- 13 mL/min, P = .001). Conversion of MMF to EC-MPS in liver transplant recipients solved the GI tolerability problems and improved renal function during the first 3 months, probably due to the concomitant reduction of anticalcineurinic dose.

Growth hormone (GH) treatment reduces peripheral thyroid hormone action in girls with Turner syndrome.

OBJECTIVE: Turner syndrome (TS) is an indication for GH therapy in spite of the modest growth response. Somatic growth depends not only on GH insulin-like growth factor I (IGF-I) axis but also on thyroid hormone (TH) status. We have previously reported that supraphysiological IGF-I levels diminished TH actions in rat tissues by reducing the nuclear TH receptor (TR). GH treatment to TS patients induces high IGF-I levels and therefore a reduction of TH action in tissues may be expected. We aimed at evaluating the effect of GH therapy in TS girls on peripheral TH action. DESIGN AND PATIENTS: We set up a reverse transcription-polymerase chain reaction (RT-PCR) for TR mRNA estimation in peripheral blood mononuclear cells (PBMC) and compared TR mRNA levels from 10 normal, 10 TS and 10 TS girls under GH therapy (0.33 mg/kg/week for 0.5-2 years). MEASUREMENTS: After RNA extraction from PBMC, TR and beta-actin mRNAs were coamplified by RT-PCR. In addition serum biochemical markers of TH action were measured: thyrotropin (TSH), sex hormone binding globulin (SHBG), osteocalcin (OC), beta-crosslaps (beta-CL), iodothyronines by electrochemiluminescency and IGF-I by immunoradiometric assay (IRMA) with extraction. RESULTS: TR mRNAs from PBMC were reduced in TS patients under GH treatment. In turn, serum TSH, OC, beta-CL and IGF-I were increased while SHBG was reduced by GH treatment in TS patients. CONCLUSIONS: GH treatment reduced TR expression in PBMC and biochemical serum markers of TH action. These results suggest that GH treatment in TS patients impair peripheral TH action at tissue level and prompt a role in the reduced growth response to the therapy.

Study of Fas (CD95) and FasL (CD178) polymorphisms in liver transplant recipients.

The Fas receptor is capable of transducing apoptotic cell death upon interaction with their ligand (FasL). Recent studies suggest that the Fas/FasL system is involved both in graft rejection and in transplantation tolerance. In this study, we analyzed the effect of Fas and FasL polymorphisms in liver allograft outcome. Fas and FasL polymorphisms were analyzed in 151 primary liver graft recipients. The Fas (-670 A/G) and the FasL (IVS2nt -124 A/G and IVS3nt 169 T/delT) polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Fas -1377 G/A polymorphism was determined by allele-specific amplification. Fas and FasL polymorphisms were not associated with acute and chronic rejection in liver transplant. In contrast, those recipients bearing the AA -670 Fas genotype showed significantly lower graft survival rate (S = 40%) than those bearing the GA genotype (S = 63.1%). These differences were detected from the first year post-transplant. Multivariate analysis confirmed that the AA genotype increased the risk of liver graft loss. This work suggests for the first time a possible harmful effect of Fas -670 AA genotype on liver graft survival, whereas the Fas and FasL polymorphisms are not associated with acute or chronic rejection in liver graft recipients.