Clinical application of the sentinel lymph node technique in early ovarian cancer: a pilot study.

INTRODUCTION: There is limited evidence favoring the use of the sentinel lymph node technique in ovarian cancer, and no standardized approach has been studied. The objective of the present pilot study is to determine the feasibility of the sentinel lymph node technique by applying a clinical algorithm. METHODS: Patients with confirmed ovarian cancer were included. 99mTc and indocyanine green were injected into the ovarian and infundubulo-pelvic ligament stump. A gamma probe and near-infrared fluorescence imaging were used for sentinel lymph node detection. RESULTS: The sentinel lymph node technique was performed in nine patients with a detection rate in the pelvic and/or para-aortic region of 100%. The tracer distribution rates of sentinel lymph nodes in the pelvic and para-aortic regions were 87.5% and 70%, respectively. CONCLUSION: The detection of sentinel lymph nodes in early-stage ovarian cancer appears to be achievable. Based on these results, a clinical trial entitled SENTOV (SENtinel lymph node Technique in OVarian cancer) will be performed.

Slap negatively regulates Src mitogenic function but does not revert Src-induced cell morphology changes.

Src-like adapter protein (Slap) is a recently identified protein that negatively regulates mitogenesis in murine fibroblasts (S. Roche, G. Alonso, A. Kazlausakas, V. M. Dixit, S. A. Courtneidge, and A. Pandey, Curr. Biol. 8:975-978, 1998) and comprises an SH3 and SH2 domain with striking identity to the corresponding Src domains. In light of this, we sought to investigate whether Slap could be an antagonist of all Src functions. Like Src, Slap was found to be myristylated in vivo and largely colocalized with Src when coexpressed in Cos7 cells. Microinjection of a Slap-expressing construct into quiescent NIH 3T3 cells inhibited platelet-derived growth factor (PDGF)-induced DNA synthesis, and the inhibition was rescued by the transcription factor c-Myc but not by c-Jun/c-Fos expression. Fyn (or Src) overexpression overrides the G(1)/S block induced by both SrcK- and a Slap mutant with a deletion of its C terminus (SlapDeltaC), but not the block induced by Slap or SlapDeltaSH3, implying that the C terminus is a noncompetitive inhibitor of Src mitogenic function. Furthermore, a chimeric adapter comprising SrcDeltaK fused to the Slap C terminus (Src/SlapC) also inhibited Src function during the PDGF response in a noncompetitive manner, as Src coexpression could not rescue PDGF signaling. Slap, however, did not reverse deregulated Src-induced cell transformation, as it was unable to inhibit depolymerization of actin stress fibers while still being able to inhibit SrcY527F-induced DNA synthesis. This was attributed to a distinct Slap SH3 binding specificity, since the chimeric Slap/SrcSH3 molecule, in which the Slap SH3 was replaced by the Src SH3 sequence, substantially restored stress fiber formation. Indeed, three amino acids important for ligand binding in Src SH3 were replaced in the Slap SH3 sequence; Slap SH3 did not bind to the Src SH3 partners p85alpha, Shc, and Sam68 in vitro, and the chimeric tyrosine kinase Slap/SrcK, composed of SlapDeltaC fused to the SH2 linker kinase sequence of Src, was not regulated in vivo. Furthermore, the Src SH3 domain is required for signaling during mitogenesis and since Slap/SrcK behaved as a dominant negative in the PDGF mitogenic response when microinjected into quiescent fibroblasts. We conclude that Slap is a negative regulator of Src during mitogenesis involving both the SH2 and the C terminus domains in a noncompetitive manner, but it does not regulate all Src function due to specific SH3 binding substrates.

Integrated pollution prevention and control for heavy ceramic industry in Galicia (NW Spain).

The heavy ceramic industry (building materials and refractory products manufacture) is an important source of pollutants to the environment. For this reason these industrial sub-sectors are included in prevention and control pollution policies, specifically those of the European Union. The IPPC Directive pays particular attention to the mineral industries, not least to the ceramic industry (epigraph 3.5, Annex I). In this paper, a methodology which is being applied to support IPPC installations and the competent administrative authority in Galicia (NW Spain) is presented. For that, the Galician heavy ceramic industry is analysed, as also are the ways to study the Best Available Techniques (BAT) with a view to establishing the emission limit values (ELV) for each specific case. Hence, a technological state of the art has been carried out for both sub-sectors, from the point of view of implementation of the IPPC in Galicia. Following this, the processes are described briefly and an analysis of the consumption and emission levels of the main pollutants is made. An inventory that includes the best environmental practices and the preventive and abatement candidate techniques as BAT was elaborated for both considered sub-sectors. An information data sheet for each candidate BAT is presented as a method to help both the industries and the competent authority to identify a candidate technique of the inventory as BAT. Three illustrative examples of the application of this procedure are presented for different emissions to environmental media for Galician installations.

Evaluation of PET texture features with heterogeneous phantoms: complementarity and effect of motion and segmentation method.

A major source of error in quantitative PET/CT scans of lung cancer tumors is respiratory motion. Regarding the variability of PET texture features (TF), the impact of respiratory motion has not been properly studied with experimental phantoms. The primary aim of this work was to evaluate the current use of PET texture analysis for heterogeneity characterization in lesions affected by respiratory motion. Twenty-eight heterogeneous lesions were simulated by a mixture of alginate and 18 F-fluoro-2-deoxy-D-glucose (FDG). Sixteen respiratory patterns were applied. Firstly, the TF response for different heterogeneous phantoms and its robustness with respect to the segmentation method were calculated. Secondly, the variability for TF derived from PET image with (gated, G-) and without (ungated, U-) motion compensation was analyzed. Finally, TF complementarity was assessed. In the comparison of TF derived from the ideal contour with respect to TF derived from 40%-threshold and adaptive-threshold PET contours, 7/8 TF showed strong linear correlation (LC) (p < 0.001, r > 0.75), despite a significant volume underestimation. Independence of lesion movement (LC in 100% of the combined pairs of movements, p < 0.05) was obtained for 1/8 TF with U-image (width of the volume-activity histogram, WH) and 4/8 TF with G-image (WH and energy (ENG), local-homogeneity (LH) and entropy (ENT), derived from the co-ocurrence matrix). Their variability in terms of the coefficient of variance ([Formula: see text]) resulted in [Formula: see text](WH) = 0.18 on the U-image and [Formula: see text](WH) = 0.24, [Formula: see text](ENG) = 0.15, [Formula: see text](LH) = 0.07 and [Formula: see text](ENT) = 0.06 on the G-image. Apart from WH (r > 0.9, p < 0.001), not one of these TF has shown LC with C max. Complementarity was observed for the TF pairs: ENG-LH, CONT (contrast)-ENT and LH-ENT. In conclusion, the effect of respiratory motion should be taken into account when the heterogeneity of lung cancer is quantified on PET/CT images. Despite inaccurate volume delineation, TF derived from 40% and COA contours could be reliable for their prognostic use. The TF that exhibited simultaneous added value and independence of lesion movement were ENG and ENT computed from the G-image. Their use is therefore recommended for heterogeneity quantification of lesions affected by respiratory motion.

177Lu-DOTATATE treatment in neuroendocrine tumours. A preliminary study. / Tratamiento con 177LU-DOTATATE en tumores neuroendocrinos. Estudio preliminar.

Therapy with radiolabelled somatostatin analogue peptides is a promising new therapy to treat neuroendocrine tumours. The aim of this preliminary study is to present our experience with 177Lu-DOTATATE therapy, and evaluate tolerability and short-term efficacy in patients with tumours expressing somatostatin receptors. A total of 7 patients with metastatic neuroendocrine tumours were treated, each with 4 doses of 177Lu-DOTATATE. The treatment response was evaluated in the form of biochemical response (tumour markers), imaging methods (somatostatin receptor scintigraphy, computed tomography, and magnetic resonance), and functional and quality of life responses using the Karnofsky performance status scale. Treatment toxicity was also evaluated. The results obtained were as follows: Biochemical response: 60% of patients showed tumour marker levels returning to normal, while they decreased significantly in the remaining 40%. Imaging response: 85.7% had a partial response, while 14.3% showed stable disease. All (100%) patients showed a significant improvement in quality of life, with increased Karnofsky scale scores. No patient had acute or chronic toxicity, and subacute transient haematological toxicity was observed in 42.8% of patients. Despite being a preliminary study, it was found that treatment with 177Lu-DOTATATE is a safe treatment with few side effects, and an objective response was achieved in most patients.

Individualised dosimetry in patients with differentiated thyroid cancer based on external dose-rate. Optimisation of the number of measurements.

OBJECTIVES: To compare the results of individual dosimetry in differentiated thyroid cancer patients treated with (131)I at our centre with the established limits and dosimetry results of published studies. Analysis of the optimal number of measurements necessary to reduce the impact of dosimetry for the comfort of the patient and, secondly, on the workload of health workers. MATERIAL AND METHODS: Dosimetry was performed in the Nuclear Medicine Department of the University and Polytechnic Hospital La Fe, on 29 patients suffering from differentiated thyroid cancer and treated with activities between 1.02 and 5.51 GBq (mean 2.68 GBq) of (131)I. The Spanish Society of Medical Physics (SEFM) protocol was used, based on measurements of external dose rate adjusted to a bi-exponential curve according to a two compartment model. Different dosimetries were performed on each patient, taking different selections of the available measurements in order to find the optimal number. RESULTS: Results are well below the dosimetry limits, and are consistent with those obtained in other centres. The number of measurements can be reduced from 5, as proposed in the SEFM protocol, to 4 without significant loss of accuracy. Further reducing measures may be justified in individual cases. CONCLUSIONS: The values obtained for the dosimetry quantities are significantly below the established limits. A reduction in measurements can be assumed at the cost of a moderate increase in uncertainty, benefiting the patient.

Effects of tumour necrosis factor-alpha on growth hormone and interleukin 6 mRNA in ovine pituitary cells.

The inflammatory cytokines tumour necrosis factor-alpha (TNF alpha), interleukin 1 (IL-1) and interleukin 6 (IL-6) have been demonstrated to influence pituitary hormone synthesis directly and via the hypothalamus. Furthermore, IL-6 is produced by some anterior pituitary cells suggesting a paracrine/autocrine role for this cytokine. We show that TNF alpha induces dispersed ovine pituitary cells to produce increased levels of growth hormone (GH) and IL-6 mRNA and secreted IL-6 in a dose and time dependent manner. TNF alpha at concentrations between 1-1000 U/ml increased GH and IL-6 mRNA, relative to control levels, by 5 h post-stimulation. For IL-6, TNF alpha increased specific mRNA at 5 h and 12 h but not 24 h post-stimulation. TNF alpha also induced secreted IL-6 to levels above that spontaneously secreted at all time points from 5 h to 48 h. Levels of common glycoprotein alpha-subunit and follicle stimulating hormone-beta (FSH beta) subunit mRNA were unaffected by TNF alpha. We conclude that TNF alpha can regulate both GH and IL-6 synthesis in dispersed ovine pituitary cells. The implications for paracrine/autocrine control of pituitary hormone synthesis in acute and chronic disease are discussed.

Radioimmunometric assay of natriuretic peptide type-B (BNP) in heart failure.

The aim of this study was to assess the value of the radioimmunometric determination of natriuretic peptide type-B (brain natriuretic peptide, BNP) in the diagnosis and prognosis of heart failure, and to study the association between BNP and the clinical, analytical and echocardiographic variables associated with the evolution of heart failure. The study group included 169 patients (74 women and 95 men; mean, 66 years) with heart failure of different causes, admitted consecutively to our hospital. BNP levels were measured with a radioimmunometric assay (Shionora BNP Cis ) after day 3 of admission. Patients were also studied by echocardiography. A significant association between the cause of heart failure and the BNP concentration was found (patients with ischaemic disease had the highest BNP values). Systolic function was worse in patients with ischaemic disease or dilated cardiomyopathy. High BNP values were also associated with advanced functional class and male sex. Plasma creatinine correlated positively with plasma BNP. However, we found no significant association with the other clinical variables evaluated. Of the echocardiographic variables analysed, BNP correlated positively with the ventricular diameter and pulmonary artery systolic pressure, and inversely with the shortening fraction; patients with severely impaired systolic function had the highest BNP values. It can be concluded that BNP levels (by radioimmunometric assay) are increased in patients with heart failure, and increase in relation to left ventricular dysfunction and the severity of heart failure. The strong independent association of plasma BNP with the left ventricular ejection fraction, its stability and the low cost of measurement suggest that plasma BNP assay could become a routine test. BNP assay could be included as an important factor in clinical and therapeutic decision making, as it complements the information provided by other variables used in the diagnosis of heart failure.

Is the depth correction using the geometric mean really necessary in a 99Tcm-DMSA scan in the paediatric population?

Determination of the left to right dimercaptosuccinic acid (DMSA) uptake ratio is theoretically one of the easiest quantitative procedures in nuclear medicine. The quantification can be performed on the posterior view, with or without the lateral view for correction of kidney depth. The geometric mean can also be determined using both the anterior and the posterior views. The aim of this study was to evaluate the occurrence of remarkable differences in the results from quantification of the relative renal function using the geometric mean and those obtained using the posterior counts only. Moreover, we evaluated to what extent the patient age influenced these differences. We reviewed 328 99Tcm-DMSA scans. The difference between the relative renal function obtained using the posterior view and that obtained using the geometric mean was calculated and analysed statistically. For the purpose of evaluating the value of performing the geometric mean calculation in patients of different ages, patients were divided into four age groups (group I, < or =2 years; group II, 3-9 years; group III, 10-18 years; group IV, >18 years). Using the Student's t test, no statistical differences were found in the relative renal function obtained by the two methods (posterior projection and geometric mean) in groups I (t = 0.01, P = 0.992) and II (t = 1.43, P = 0.155), which consisted of patients younger than 10 years (77% of the patients). In groups III and IV statistical differences were found (t = 2.27, P = 0.028 and t = 2.170, P = 0.038), respectively. We conclude that for children under 10 years it is unnecessary to perform depth correction using the geometric mean except in rare cases of major malformations and position anomalies.

Radioimmunometric assay of B-type natriuretic peptide (BNP) in heart transplantation: correlation between BNP determinations and biopsy grading of rejection.

The aim of this study was to determine whether elevated brain natriuretic peptide (BNP) levels after heart transplantation are correlated with the severity of rejection by using endomyocardial biopsy (EMB) and echocardiographic parameters indicative of ventricular function of the transplanted heart. This was an observational study of 80 orthotopic heart transplant recipients (11 women and 69 men; mean age 53+/-11 years). BNP determinations were performed within 48 h of endomyocardial biopsy. The echocardiographic study and BNP determination were also performed in a group of healthy volunteers. We found significantly higher BNP mean levels in heart transplant patients than in healthy volunteers (volunteers, 16.7+/-16.2 pg.ml-1; transplant, 213.4+/-268.6 pg.ml-1; P<0.001). Transplant recipients with rejection grades 2, 3 and 4 on EMB had significantly higher BNP levels than those with rejection grades 0 and 1 (higher rejection grade, 162.5+/-168.4 pg.ml-1; lower rejection grade, 292+/-361.8 pg.ml-1; P<0.01). BNP values of patients with good left ventricular function (LVF) were significantly lower than in patients with mildly and moderately impaired LVF and patients with severely impaired LVF (good function, 199.76+/-233.6 pg.ml-1; mildly/moderately impaired LVF, 937+/-644.5 pg.ml-1; severely impaired LVF, 1038+/-491.2 pg.ml-1; P<0.001). It is concluded that BNP plasma levels are elevated in heart transplant patients compared to the normal population. The distribution of BNP levels in heart transplanted patients show a wide range. BNP elevation is greater in patients with higher rejection grades on EMB and greater impairment of left ventricular function.

Microvascularized fibular graft for mandibular reconstruction: detection of viability by bone scintigraphy and SPECT.

Bone allografts are often used in reconstructive mandibular surgery, generally after extensive oncologic resection, post-traumatic pseudoarthrosis, or osteomyelitis. Vascularized fibular bone grafts have advantages compared with other bone grafts in the restoration of the contour and function of defective mandibles. Bone scintigraphy is often used to assess bone revascularization, because positive uptake of Tc-99m hydroxy methylene diphosphonate (HDP) reflects patent anastomoses and viability of the grafted bone. Mandibular reconstruction with a free fibular flap was performed in 11 patients. Bone scintigraphy and SPECT were applied in the follow-up of eight patients. The grafts were assessed semi-quantitatively using a six-grade scoring system based on a comparison of tracer uptake in the graft and in the calvarium. Complications were observed in one graft. Planar scintigrams showed a tracer uptake greater than grade 5 in grafts with an uncomplicated course. SPECT was performed in addition to planar imaging in two patients who had greater graft uptake. A lack of tracer uptake was observed in the failed graft. Bone scintigraphy performed within the first week after the mandibular reconstruction is a useful tool to monitor the viability and early complications of microvascularized fibular grafts and plays an important role in the decision-making process during repeated surgical exploration. SPECT is more sensitive than planar imaging for assessing graft viability.

[Massive venous thrombosis with cardiac invasion as primary manifestation of hepatocarcinoma]. / Trombosis venosa masiva con invasión cardiaca como primera manifestación de un hepatocarcinoma.

Hepatocellular carcinoma has a tendency to invade vascular structures. However, extension into the hepatic veins or heart is uncommon. We describe the case of a 68 years old man with chronic viral hepatitis type C, consulting about edema and pain in his left leg. Doppler scan showed deep venous thrombosis in that level and computed tomography of thorax and abdomen showed complete thrombosis of the inferior cava vein, thrombosis of the left suprahepatic vein, a voluminous thrombus in the right atrium and an irregular mass in the liver. Alpha-fetoprotein was 77,046 ng/ml The biopsy of the rigth atrium thrombus demonstrated diseminated hepatocellular carcinoma. We comment the patient progress after surgery, the incidence, clinical symptoms, and therapy options for these patients.

[Bone scintigraphy and somatostatin receptor scintigraphy in pediatric patients with bone involvement in Langerhans cell histiocytosis]. / Gammagrafía ósea y gammagrafía de receptores de la somatostatina en pacientes pediátricos con histiocitosis de células de Langerhans ósea.

Langerhans cell histiocytosis (LCH) is a granulomatous disease which can involve multiples sites of the body. Diagnostic imaging is of utmost importance in the management of these patients. Up to now radiographic skeletal survey and bone scintigraphy (BS) have been used to assess bone involvement (both with low specificity). Magnetic resonance imaging (MRI) and CT have been used to assess visceral involvement but with the limitation that they cannot give information about the functional status. Recently somatostatin receptor scintigraphy (SSRS) has been proposed to detect active lesions and to monitor response to treatment. The aim of this study is to assess bone and somatostatin receptor scintigraphy in the detection of bone involvement in LCH in children. Twenty scintigraphies (12 SSRS and 8 BS) were performed in seven patients (3 girls and 4 boys) aged at diagnosis: 18 month-12 years (mean age 6 years). The findings obtained in the scintigraphies were compared with clinical evolution and other imaging techniques. Bone scintigraphy detected all the LCH bone lesions, and discovered one unknown lesion. SSRS scintigraphy visualised the active lesions in 3 patients (clinical and other imaging techniques were also positive). SSRS was negative in one patient classified as disease free and another in clinical remission. SSRS detected 2 new unknown bone lesions, but could not detect LCH bone lesions confirmed in other imaging techniques in 2 patients. Somatostatin receptor and Bone scintigraphy can be used to detect active LCH bone lesions in children and can help to monitor response to treatment. Further studies with more patients are needed to confirm the diagnostic usefulness of these techniques.

Intervención educativa de enfermería para fomentar el autocuidado de la mujer durante el climaterio / Nursing educational intervention to foster women's self-care during their climacteric period / Intervenção educativa de enfermagem para o autocuidado em mulheres durante o climatério

Objetivo: Evaluar las intervenciones educativas de enfermería para el autocuidado en las mujeres durante el climaterio. Método: Cuantitativo, cuasiexperimental y transversal. Muestreo de tipo no probabilístico en el que participaron 30 mujeres. Se aplicaron 2 instrumentos: Uno que incluyó datos sociodemográficos y el otro, un cuestionario de autocuidado. Se llevó a cabo en 3 etapas: Diagnóstica, de intervención y de evaluación. Se aplicó prueba de t de Student no paramétrica para comparar grupos dependientes. Resultados: Antes de las intervenciones educativas del personal de enfermería, el 90% de las mujeres refirieron un autocuidado regular, el 6.7% bueno y el 3.3% malo; después del programa de intervenciones, el 60% refieren autocuidado regular y el 40%, bueno. Conclusión: Las intervenciones educativas de enfermería para el autocuidado -mediante la aplicación de un programa- dirigido a mujeres durante el climaterio, permitieron modificar el autocuidado al contribuir en la concientización, toma de decisiones, cambios de conducta. De tal forma que la participación de enfermería dentro de la promoción de la salud es fundamental, ya que busca el bienestar integral y el desarrollo de la mujer en esta etapa de la vida.

Objective: To assess nursing educational interventions fostering women's self-care during their climacteric period. Method: This is a quantitative, quasi-experimental, and transversal study with non-probabilistic sampling. Thirty women participated. Two instruments were used: One to gather social and demographic data, and the other to obtain the self-care data. The study was carried out in 3 stages: Diagnosis, intervention, and evaluation. The non-parametric Student's t test was calculated to compare dependent groups. Results: Before the interventions, 90% of the women referred having a just-fair self-care level, while 6.7% a good one, and 3.3% a bad one. After the interventions program, 60% of the women referred having a just-fair self-care level, but 40% reported a good one. Conclusion: Nursing educational interventions fostering women's self-care during their climacteric period led to a positive modification of self-care behaviors among these women by contributing to their awareness and good decision-making. Nursing participation in the promotion of health is fundamental, including women's wellbeing during this difficult stage of their lives.

Objetivo: Avaliar as intervenções educativas de enfermagem para o autocuidado nas mulheres durante o climatério. Método: Quantitativo, quase experimental e transversal. Amostragem de tipo não probabilística, participaram 30 mulheres. Aplicaram-se 2 instrumentos, um que incluiu dados sociodemográficos e o questionário de autocuidado. Executou-se em três etapas: Diagnóstica, de intervenção e de avaliação. Aplicou-se prova de t de Student não paramédica para comparar grupos dependentes. Resultados: Antes das intervenções educativas do pessoal de enfermagem, o 90% das mulheres referiram um autocuidado regular, 6.7% bom e 3.3% mau, depois do programa de intervenções, 60% referem autocuidado regular e 40% bom. Conclusão: As intervenções educativas de enfermagem para o autocuidado-mediante a aplicação do programa- dirigido a mulheres durante o climatério permitiram modificar o autocuidado para contribuir na conscientização, tomada de decisões, mudanças de conduta. De tal forma que a participação de enfermagem dentro da promoção da saúde é fundamental, dado que procura o bem-estar integral e o desenvolvimento da mulher nesta etapa da vida.

Sympathetic reinnervation 1 year after heart transplantation, assessed using iodine-123 metaiodobenzylguanidine imaging.

Complete allograft denervation occurs during heart transplantation (HT). Partial ventricular sympathetic reinnervation that may develop after transplantation can be measured using iodine-123 meta iodobenzylguanidine (MIBG) uptake. Previous studies have suggested that reinnervation is likely to be a slow process, only occurring after 1 year posttransplantation. However, the reinnervation prevalence at 1 year after HT remains unknown. This study sought to determine sympathetic reinnervation measured by MIBG at 12 months after surgery. We performed serial cardiac MIBG imaging in 45 cardiac transplant recipients, including 32 males and 13 females, early (2 months) and late (12 months) after the operation. The intensity of myocardial MIBG uptaken was quantified by heart-to-mediastinum ratios (HMR). Reinnervation was considered when the HMR was >1.3. HMR was significantly higher at 12 months: 1.16 ± 0.10 at 2 vs 1.30 ± 0.15 at 12 months (P < .001). Eighteen (40%) of 45 subjects developed visible cardiac MIBG uptake at 1 year after transplantation with HMR >1.3. In conclusion, partial sympathetic reinnervation increases with time after HT; it was seen in 40% of patients at 1 year after the operation.