Assessment of Kidney Graft Function Evolution Measured by Creatinine and Cystatin C.

INTRODUCTION: The 2013 Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline suggests measuring cystatin C (sCys) in adults with glomerular filtration rate (GFR) based on creatinine (sCr) between 45 and 59 mL/min/1.73 m2 if confirmation of chronic kidney disease (CKD) is required. There is not enough evidence to recommend the use of sCys or sCr to estimate GFR in kidney transplant recipients. OBJECTIVES: Our aims were to describe the evolution of sCr, sCys, and GFR in a group of kidney transplant patients and to determine their association with some markers of morbidity at 1 year. METHODS: A total of 54 patients were included. Analytical and clinical data were recorded. Renal function was analyzed using the CKD Epidemiology Collaboration (EPI) sCr equation and CKD-EPI sCys equation. RESULTS: sCys-estimated GFR was higher than estimated from sCr by CKD-EPI. The values of sCys have more variability than those of sCr. The agreement between the stages of CKD by sCr or sCys-estimated GFR measured by Cohen's kappa coefficient was only fair. One-year CKD-associated variables correlated differently with sCr and sCys-estimated GFR. Hemoglobin, uric acid, calcium, and phosphorus related to sCr-estimated GFR, whereas serum albumin was associated with sCys-estimated GFR. CONCLUSIONS: sCys values have a higher variability than sCr in kidney transplant recipients. sCys- or sCr-based GFRs have a nonsimilar behavior in these patients with weak agreement to stratify CKD stages and a different relationship to CKD-related comorbid conditions.

[Analysis of small areas of pediatric cancer in the municipality of Murcia (Spain)]. / Análisis en áreas pequeñas del cáncer pediátrico en el municipio de Murcia.

INTRODUCTION: Occasionally, primary care pediatricians notice the presence of small clusters of pediatric cancer (PC), but are often frustrated by the findings after statistical analysis. The study of small areas in spatial epidemiology has led to advances in identifying clusters and the environmental risk factors involved. The purpose of this study was to describe the PC incidence and the spatial distribution at the minimum level of disaggregation possible in Murcia, presenting the first urban municipality map of PC in Spain. MATERIALS AND METHODS: A population-based descriptive study was conducted on the PC cases diagnosed in children younger than 15 years, between 1998 and 2013 in the municipality of Murcia. Cases were classified by sex, age group, and tumor type. Coordinates of home addresses at the time of diagnosis were assigned to each case, and spatial and spatio-temporal analyses were carried out at the level of census tracts, using FleXScan and SatScan. RESULTS: A total of 155 cases of PC were diagnosed during this period. The overall incidence of PC (138/10(6) of children under the age of 15) and the incidence for individual tumor types were within the expected ranges for Europe. A spatio-temporal cluster of Hodgkin lymphoma was identified. CONCLUSIONS: Small area analysis of PC cases may be a useful tool for the identification of PC clusters, which would allow for the generation of hypotheses regarding disease etiology, as well as developing urban models for environmental surveillance of PC.

[Long-term follow up of childhood cancer survivors in the Murcia Region: preferences and attitudes of Primary Care professionals]. / Programa de largo seguimiento de supervivientes de cáncer pediátrico en la Región de Murcia: preferencias y actitudes de los profesionales de Atención Primaria.

OBJECTIVE: To assess attitudes, beliefs and knowledge of primary medical care professionals as regards the follow-up of Childhood Cancer Survivors (CCS) and the introduction of a Long-Term Follow-Up Program for Childhood Cancer Survivors in the Region of Murcia (PLASESCAP-MUR). MATERIAL AND METHODS: Descriptive cross-sectional study using a structured, self-administered questionnaire. These questionnaires were sent to all primary medical care professionals in Murcia Health District 1. RESULTS: Response rate of 58% (100/172), with 71% and 22% being family physicians and pediatricians, respectively, of whom 49% provided medical care to a CCS in the last 5 years, with 84% reporting that they never or rarely received a detailed report of overall assessment of the survivor. More than 75% found that access to detailed follow-up information was quite or very useful; 95% prefer to consult experts when providing medical care to survivors, and 80% believe that improving the quality of the environment may decrease the morbidity and mortality of the survivors. A statistically significant relationship was found between the length of practicing medicine and the perception of the importance of environmental factors. CONCLUSIONS: It seems to be important to increase the training of primary care professionals for the long-term follow-up of CCS, as well as having the detailed information through a personalized long-term follow-up of each survivor. PLASESCAP-MUR offers an integrated follow-up to CCS in a model of shared care between Long Term Monitoring Units and Primary Care Units.

[The association of adherence to a Mediterranean diet during early pregnancy and the risk of gastroschisis in the offspring]. / Asociación de la adherencia a la dieta mediterránea al inicio del embarazo y riesgo de gastrosquisis en la descendencia: un estudio de casos-controles.

OBJECTIVES: The aim of this study was to study the association of adherence to the Mediterranean diet in early pregnancy maternal and the offspring's risk of gastroschisis. METHODS: Case-control study. We describe 11 cases of gastroschisis in the region of Murcia from 2007 to 2012 and 34 concurrent controls. At the time of diagnosis each of the cases completed a validated Food Frequency Questionnaire (FFQ) consisting of 98 items on the periconceptional diet. Confounding factors: smoking, exposure to cannabis / marihuana, age of the parents, BMI, income and educational level. We conducted a descriptive and multivariate logistic regression statistical analysis. RESULTS: Mothers of children with gastroschisis were younger (20.8 years, 95% CI 17.3 to 24.2) and their diet consisted of less caloric intake, saturated fat and monounsaturated fats and proteins than controls. The Odds Ratio (OR) in the multivariate model controlling for confounding factors: maternal age (year) 0.70 (95% CI 0.51 to 0.96), monounsaturated fatty acids (oleic acid, g) 0.79 (95% CI 0.65 to 0, 97) and vegetable intake (rations/week) 0.70 (95% CI 0.48 to 1.00). CONCLUSION: A maternal diet rich in oleic acid and vegetable products may prevent vascular risk of onphalomesenteric arteries reducing the risk of gastroschisis.

[Environment and paediatric cancer in the Region of Murcia (Spain): integrating clinical and environmental history in a geographic information system]. / Medio ambiente y cáncer pediátrico en la Región de Murcia (España): integrando la historia clínica medioambiental en un sistema de información geográfica.

INTRODUCTION: Environment and Paediatric Cancer (PC) in the Region of Murcia (RM) is an on-going research project that has the following aims: to collect a careful paediatric environmental history (PEH) and to use geographical information systems (GIS) to map the incidence and analyze the geographic distribution of the PC incidence in the RM. The objectives are to present the methodology used for the collection and processing of data and disseminate initial results on the spatial and temporal incidence of PC in the RM (Spain). MATERIAL AND METHODS: A descriptive and georeference study of all PC cases under 15 years, diagnosed from 1 January 1998 to December 31, 2009. Three postal addresses were assigned to each case, residence during pregnancy, postnatal, and at the time of diagnosis. Other variables such as sex, date of birth, date of diagnosis, and histopathology classification were collected. RESULTS: No increase was observed in the trend of incidence of PC. The crude annual incidence rate was 14.3 cases per 100,000 children under 15 years. The standardised incidence ratio was higher in the north-west of the RM. Before diagnosis, 30% of cases had a different postal address than during the pregnancy. CONCLUSIONS: Integrating the spatial and temporal information through the PEH in a GIS should allow the identification and study of space-time clusters through an environmental monitoring system in order to know the importance of associated risk factors.

Apoptotic volume decrease as a geometric determinant for cell dismantling into apoptotic bodies.

Apoptosis is a mode of cell death through which cells are dismantled and cell remains are packed into small, membrane-bound, sealed vesicles called apoptotic bodies, which are easy to erase by phagocytosis by neighbouring and immune system cells. The end point of the process is to cleanly eliminate damaged or unnecessary cells without disrupting the surrounding tissue or eliciting an inflammatory response. The apoptotic process involves a series of specific events including deoxyribonucleic acid and nuclear fragmentation, protease-driven cleavage of specific substrates, which inhibits key survival functions and reorganizes the cell's structure, externalization of molecules involved in phagocytosis, membrane blebbing and cell shrinkage. Apoptotic volume decrease (AVD) leading to cell shrinkage is a core event in the course of apoptosis, the biological meaning of which has not been clearly ascertained. In this article we argue that volume loss is a geometrical requisite for cell dismantling into apoptotic bodies. This is derived from the cell's volume-to-surface ratio. Indeed, package of the original cell volume into smaller membrane-sealed vesicles requires that either cell membrane surface increase or cell volume decrease. In this sense, AVD provides a reservoir of membrane surface for apoptotic body formation. The strategic situation of AVD in the time course of apoptosis is also discussed in the context of apoptotic body formation.

[Bidimensional-ultrasound guided-craniotomy in the excision of supratentorial brain tumours]. / Craneotomía guiada por ultrasonografía bidimensional para exéresis de tumor cerebral supratentorial.

OBJECTIVES: With this 1-year retrospective study we aimed to analyze our experience on the utilization of real-time bidimensional (2-D) ultrasonography as an aid for the localization of deep-seated supratentorial brain tumours. MATERIAL AND METHODS: During the year 2006 we performed 2-D ultrasonographic localization studies in patients undergoing excision of subcortical supratentorial brain tumours whose nature was pathologically proven. The ultrasound machines utilized were 2410 A ultrasounds HP and Phillips HDI 3500 ATL. To check gross anatomical structures we used a 3 MHz probe and then a 5 MHz sound to define the brain tumour characteristics. Coronal and sagittal cuts were obtained during parietal or temporal craniotomies, and axial and sagittal slices in the case of frontal masses. After brain tumour removal and after a thorough irrigation with saline, new image acquisitions were performed to confirm the completeness of tumour excision. The amount of removed tumour was also verified by a post-contrast computerized tomography (CT) scan performed after the surgery. RESULTS: The study group was composed by 30 patients with ages comprised between 28 and 82 years. The time required for tumour localization was 17.5 (+/- 1.9) min. The lesions were approached though 8 temporal, 7 parieto-occipital, 8 parietal, 2 fronto-parietal and 5 temporo-parietal craniotomies. Mean depth of the lesions was 5.3 (+/- 1.6) cm. The histopathologic diagnosis was 17 high-grade gliomas, 3 low-grade astrocytomas, 8 metastatic lesions and 2 oligo-astrocytomas. High-grade gliomas were more echogenic than low-grade tumours and than oedema. No residual tumour was detected at the end of the surgery except in two cases in which a tumoral rest was left due to the proximity of the lesion to eloquent cerebral areas. Postoperative CT scans confirmed the completeness of tumour removal in the patients of the study as assessed by intraoperative ultrasounds. CONCLUSIONS: Real-time 2-D ultrasonography affords an adequate image quality for performing guided-craniotomy in supratentorial brain tumours, as it allows for a safe and accurate localization of the lesions. Its use is mainly indicated in the removal of tumours located in, or close to, important anatomical and functional brain areas and to depict the presence of tumour rests after surgical removal of cerebral neoplasms.

[Postoperative delirium in patient neurosurgical: evaluation by means of the Abbreviated Mental Test]. / Delirio postoperatorio en pacientes neuroquirúrgicos: evaluación mediante el Test Mental Abreviado.

OBJECTIVES: To assess the incidence and characteristics of postoperative changes in the higher cerebral functions after elective intracranial surgery under general anesthesia. PATIENTS AND METHODS: This is a prospective study of 60 patients, aged 18-81 years, submitted to neurosurgical operations, allocated into two groups of 30 patients each: intracranial surgery group, patients submitted to craniotomy, and extracranial surgery group or control group, patients submitted to spinal procedures. All patients were given the Abbreviated Mental Test (AMT) on the day before to the operation, and then 2 and 24 hours after the end of the procedure. All individuals were managed with the same anesthetic technique. RESULTS: No differences in regard to demographics, duration of the operation, ASA physical state, and habits were found between the two groups. No differences in the pre-surgical and post-surgical AMT mean score were encountered between patients submitted to intracranial 9.87 +/- 0.35 or to spinal surgeries 9.80 +/- 0.41. Similarly, there were no significant differences between the two groups in the results of the AMT performed at 2 and 24 hours after the end of the surgeries. Only two subjects undergoing spinal procedures had a score of < or = 8 in the AMT performed 2-hours after the operation, while none showed a decrease in the 24-hour test score. CONCLUSIONS: Patients submitted to intracranial surgery did not show any changes in cognitive or attention functions during the first postoperative 24 hours as assessed by the AMT.

[Comparison of anesthetic maintenance and recovery with propofol versus sevoflurane combined with remifentanil in craniotomy for supratentorial neoplasm]. / Estudio comparativo de remifentanilo combinado con propofol o sevofluorano para el mantenimiento y recuperación de la anestesia en craneotomía por neoplasia supratentorial.

OBJECTIVE: To compare the effectiveness of propofol versus sevoflurane associated with remifentanil on the maintenance of anesthesia and on recovery in patients undergoing elective supratentorial craniotomy. PATIENTS AND METHODS: Prospective randomized trial enrolling 90 patients scheduled for excision of a brain neoplasm. All received an infusion of remifentanil at a dose of 0.5 microg x Kg(-1) x min(-1) until tracheal intubation and then 0.25 microg x Kg(-1) x min(-1) during surgery. Induction was achieved with propofol and anesthesia was maintained with either sevoflurane at a maximum alveolar concentration of 0.4 (45 patients) or propofol by target controlled infusion at a concentration of 2.5 microg x mL(-1) (45 patients, group P). Variables assessed were hemodynamic stability during anesthesia and times and quality of recovery from anesthesia (eye opening, initiation of spontaneous ventilation, extubation, cough reflex, and temporal and spacial orientation 3 minutes after extubation. During the first 24 hours after surgery, pain intensity was evaluated on a verbal visual analog scale (VAS) and the incidence of nausea and vomiting was recorded. RESULTS: Times until eye opening upon request and until extubation were significantly shorter in the sevoflurane group than in the propofol group: 3.7 (SD, 1.2) minutes vs 5 (3.1) minutes, respectively, for eye opening and 6.6 (1.2) minutes vs 8.1 (3.3) minutes for extubation (P<0.01). The incidence of nausea and vomiting was significantly higher in the sevoflurane group (40% vs 13%, respectively, P<0.01). CONCLUSIONS: Combining remifentanil with propofol or with sevoflurane provides satisfactory anesthesia during elective supratentorial craniotomy to remove a brain neoplasm. Hemodynamic stability is appropriate and recovery from anesthesia is rapid.

[Tension pneumocephalus after intracranial surgery in the supine position]. / Neumoencéfalo a tensión tras cirugía intracraneal en posición supina.

Tension pneumocephalus is a rare and severe complication appearing after posterior fossa procedures in the sitting position. This complication may endanger the patient's life and require immediate treatment. However, tension pneumocephalus after neurosurgical procedure in the supine position have been scarcely reported. We report such a complication occurring in a 14-year-old girl submitted to a frontotemporal craniotomy for removal of an astrocytome performed with the patient supine. We discuss ethiopathogenesis and management of this complication.

Retinoid-related molecules require caspase 9 for the effective release of Smac and the rapid induction of apoptosis.

Certain retinoid-related molecules (RRMs) with agonist or antagonist activities have been described to induce apoptosis in a variety of cancer cell lines and show promise for the treatment of cancer. Similar to other chemotherapeutic drugs, these retinoid analogs have been suggested to induce apoptosis through the intrinsic pathway, which requires the release of cytochrome c from the mitochondria for the effective activation of caspase 9. Expression of a catalytically inactive form of caspase 9, which functions as a dominant negative mutant, inhibits the induction of DEVDase activity and nuclear fragmentation by selective RRMs. Whereas the RRMs could induce the release of cytochrome c in the absence of caspase 9 activity, the later is necessary for the effective release of Smac/Diablo from the mitochondria. Furthermore, overexpression of Bcl-2 or Bcl-X(L) also inhibits RRM-induced apoptosis. We demonstrate that activation of caspase 2 by the agonist MX2870-1 requires caspase 9 activity and is inhibited by Bcl-2 overexpression. In contrast, the antagonist MX781 induces cleavage of procaspase 2 upstream of mitochondria and independently of caspase 9. Thus, two retinoid analogs with unique characteristics activate two distinct apical caspases (2 or 9) to initiate apoptosis. In addition to caspase-mediated cell death, sustained exposure to the RRMs can also lead to loss of cell viability in cells lacking caspase 9 activity or in cells stimulated in the presence of the caspase inhibitor Z-VAD-fmk. Moreover, MX2870-1 and MX781 produce cell cycle arrest independently of caspase activity and the retinoid receptors.

[Cerebral activation during Stroop's test in a case of early focal brain injury]. / Activación cerebral durante el test de Stroop en un caso de lesión cerebral focal temprana.

INTRODUCTION: Functional magnetic resonance imaging (fMRI) offers an important advantage over other functional neuroimaging techniques used with children because of its harmlessness. Previous studies conducted with adults with alexia suggested two ways the brain can reorganise reading after a brain injury affecting the left hemisphere, one contralateral and the other ipsilateral. CASE REPORT: We describe a study carried out using fMRI of a 10 year old girl with an injury to the left hemisphere caused by a fishing harpoon when she was 6 years old. As a result of the accident the girl presented a right hemiparesia. The girl s parents and teachers also reported difficulties in the acquisition of reading writing and arithmetic, as well as a certain degree of attentional deficit. An fMRI exploration was performed while the girl was doing the Stroop test. The structural MR images showed left hemisphere cortical lesions in the orbital and angular gyrus regions, in addition to the caudate and putamen nuclei, and in the inferior longitudinal bundle. The fRMI revealed a strong overactivation of the right dorsolateral frontal cortex, in the evaluation of interference, and activations of the right angular and bilateral supramarginal gyri, in the evaluation of word reading. CONCLUSION: The functional study suggests the existence of a reorganisation of reading that is both intra and inter hemispheric.

Retinoid-related molecules induce cytochrome c release and apoptosis through activation of c-Jun NH(2)-terminal kinase/p38 mitogen-activated protein kinases.

Retinoid-related molecules have been described that induce apoptosis in a variety of cancer cell lines. Of particular interest is the apoptotic activity of the all-trans-retinoic acid receptor gamma-selective molecules MX2870-1 and MX3350-1. These compounds have been shown to be effective in vivo against lung cancer and could therefore serve as important leads for novel anticancer drugs. We analyzed the death signaling pathways activated by these molecules. We observed that apoptotic retinoid-related molecules (RRMs) cause the release of cytochrome c from the mitochondria and subsequent activation of caspases 9 and 3. This was preceded by a strong and sustained activation of c-Jun NH(2)-terminal kinase as well as p38 kinase, which was independent of caspase activity. Inhibition of p38 kinase activity by the specific inhibitor SB203580 did not affect the induction of apoptosis by MX2870-1. However, interference with the activation of c-Jun NH(2)-terminal kinase and p38 stress kinases by PD169316 completely blocked all signs of apoptosis, including caspase activity, DNA fragmentation, and phosphatidylserine externalization. PD169316 also prevented the cleavage of Bid and the release of cytochrome c induced by this class of RRMs. Furthermore, processing and activation of different caspases by MX2870-1 was completely inhibited by increasing concentrations of PD169316. Thus, the investigated RRMs induce a death pathway, which is independent of Fas ligand, that is also activated by UV radiation and other agents. Our findings open the possibility for the future use of this class of RRMs in combination therapies with other anticancer drugs.

[Spontaneous rhinorrhea due to basal encephalocele]. / Rinorrea espontánea por encefalocele basal.

We report the case of a 4-year-old girl who presented spontaneous watery discharge through the left nostril due to a basal encephalocele. Two infrequent operative findings were the presence of an excavation of the cribriform plate, and not of a true osseous defect, and the absence of the left olfactory bulb.

Mesenteric cyclooxygenase products after combined antihypertensive treatment in uninephrectomized SHRs.

Unilateral nephrectomy in the spontaneously hypertensive rat (SHR) does not produce any change in blood pressure but does induce humoral alterations that might influence the antihypertensive action of some drugs. In this study, the antihypertensive effect of treatment (5 weeks) with placebo (control), verapamil, trandolapril, or their combination (verapamil plus trandolapril) was investigated in SHRs with half renal mass ablation, regarding the structure and function of small mesenteric arteries. Arterial pressure was followed during the period of treatment. Trandolapril and veratran returned pressure to normal, while verapamil was ineffective. Statistically significant differences in the parameters of vessel structure were not observed among groups; thus, the alterations in functionality cannot be attributed to morphologic changes. The noradrenaline-induced contraction was reduced similarly by the three treatments as compared to controls. This difference involved a higher participation of nitric oxide in the trandolapril group, while in the verapamil group the origin of the difference might be due to the abolishment of a cyclooxygenase product. Veratran retained both effects. Acetylcholine-evoked relaxation of vessels precontracted with noradrenaline was improved with treatments versus controls. The abolishment of a contracting prostanoid or an NO scavenger from the cyclooxygenase pathway, due to the treatments implemented, is probably the cause of this.

Antihypertensive effect of trandolapril and verapamil in rats with induced hypertension.

The antihypertensive effect of long-term treatment (6 months) with placebo (as control), verapamil, trandolapril, and their combination (verapamil plus trandolapril) was investigated in Wistar rats rendered hypertensive by extensive renal mass ablation, as a model lacking genetic hypertensive determinants. Arterial pressure was monitored during treatment and at the end, aortic structure and functionality were investigated. Trandolapril and the combination prevented the increase in pressure observed in the control group after renal handicap, whereas verapamil was much less effective. Trandolapril and the combination were similarly effective, whereas verapamil was ineffective, or even deleterious, at reducing aortic lamina media hypertrophy, the wall-to-lumen ratio, lamina media cross-sectional area, potassium chloride-induced contraction, and at increasing acetylcholine relaxation. The response to noradrenaline decreased in the trandolapril group, increased in the verapamil group, and remained unmodified in the association group. In conclusion, treatment with trandolapril exerts beneficial antihypertensive actions in this model of induced hypertension, showing continuous control of blood pressure and prevention of structural and functional alteration of the aorta. Verapamil exerts weak control of arterial pressure and produces, if any, deleterious effects on the structure and function of the aorta. These negative effects of verapamil are overcome by coadministration of trandolapril.

Antihypertensive action of trandolapril and verapamil in spontaneously hypertensive rats after unilateral nephrectomy.

It is well documented that the kidney plays a fundamental role in long-term arterial pressure regulation, and, as an endocrine organ, in the regulation of cardiovascular structure and functionality. In this study, the antihypertensive effect of long-term treatment (6 months) with placebo, verapamil, trandolapril, and a combination of the latter (verapamil plus trandolapril) was investigated in spontaneously hypertensive rats after half-renal-mass ablation. Arterial pressure was monitored during treatment and at the end, aortic structure and functionality were investigated. Trandolapril and the combination returned pressure to normal, whereas verapamil was less effective. All three treatment groups were similarly effective at reducing aortic medial hypertrophy, the wall-to-lumen ratio, and contraction evoked by potassium chloride and noradrenaline. Verapamil and veratran were more effective than trandolapril at reducing lamina media cross-sectional area. Trandolapril and the combination were more effective than verapamil at improving endothelial dysfunction.

A non-linear least-squares approach to the resolution of heterogeneous fluorescence from multitryptophan proteins.

Protein heterogeneous fluorescence results from the different microenvironment of each emitting chromophore. The structural and dynamic information contained in this emission can be extracted to some extent by selective quenching experiments. In this work, graphical and numerical methods are described for the analysis of protein emission in terms of three separated contributions: a fluorescence fraction which is not accessible to the quencher and two additional fractions with different solvent exposure. 'Static quenching' deviations from Stern-Volmer behaviour are also discussed. The application of these methods is exemplified on simulated quenching experiments and real data on acrylamide quenching of lysozyme fluorescence.