Study of tocopherol content and its potential antioxidant activity in commercial lipid emulsions for parenteral nutrition.

The objective of this study was to determine the content and evaluate the potential antioxidant effect of tocopherols in commercially available lipid emulsions, using a simple validated method adequate for further routine use. During the study, variability between manufacturers as well as between three non-consecutive batches of the same emulsion was observed. Furthermore, addition of α-tocopherol to lipid emulsions as excipient yields more stable emulsions and potentially a beneficial clinical effect. It was concluded that the variation of the tocopherol content between batches implies the importance of control and specification of tocopherol content by the manufacturers.

Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated. METHODS: FXR and TGR5 expression was determined in human CCA tissues and cell lines. An orthotopic model of CCA was established in immunodeficient mice and tumor volume was monitored by magnetic resonance imaging under chronic administration of the specific FXR or TGR5 agonists, obeticholic acid (OCA) or INT-777 (0,03% in chow; Intercept Pharmaceuticals), respectively. Functional effects of FXR or TGR5 activation were evaluated on CCA cells in vitro. RESULTS: FXR was downregulated whereas TGR5 was upregulated in human CCA tissues compared to surrounding normal liver tissue. FXR expression correlated with tumor differentiation and TGR5 correlated with perineural invasion. TGR5 expression was higher in perihilar than in intrahepatic CCAs. In vitro, FXR was downregulated and TGR5 was upregulated in human CCA cells compared to normal human cholangiocytes. OCA halted CCA growth in vivo, whereas INT-777 showed no effect. In vitro, OCA inhibited CCA cell proliferation and migration which was associated with decreased mitochondrial energy metabolism. INT-777, by contrast, stimulated CCA cell proliferation and migration, linked to increased mitochondrial energy metabolism. CONCLUSION: Activation of FXR inhibits, whereas TGR5 activation may promote, CCA progression by regulating proliferation, migration and mitochondrial energy metabolism. Modulation of FXR or TGR5 activities may represent potential therapeutic strategies for CCA.

Synthesis and functionalization of dextran-based single-chain nanoparticles in aqueous media.

Water-dispersible dextran-based single-chain polymer nanoparticles (SCPNs) were prepared in aqueous media and under mild conditions. Radiolabeling of the resulting biocompatible materials allowed the study of lung deposition of aqueous aerosols after intratracheal nebulization by means of single-photon emission computed tomography (SPECT), demonstrating their potential use as imaging contrast agents.

Ion beam induced 18F-radiofluorination: straightforward synthesis of gaseous radiotracers for the assessment of regional lung ventilation using positron emission tomography.

A simple, straightforward and efficient method for the synthesis of [18F]CF4 and [18F]SF6 based on an ion beam-induced isotopic exchange reaction is presented. Positron emission tomography ventilation studies in rodents using [18F]CF4 showed a uniform distribution of the radiofluorinated gas within the lungs and rapid elimination after discontinuation of the administration.

Straightforward synthesis of radioiodinated Cc-substituted o-carboranes: towards a versatile platform to enable the in vivo assessment of BNCT drug candidates.

Due to their high boron content and rich chemistry, dicarba-closo-dodecaboranes (carboranes) are promising building blocks for the development of drug candidates with application in Boron Neutron Capture Therapy. However, the non-invasive determination of their pharmacokinetic properties to predict therapeutic efficacy is still a challenge. Herein, we have reported the unprecedented preparation of mono-[(125)I] iodinated decaborane via a catalyst-assisted isotopic exchange. Subsequent reactions of the radiolabelled species with acetylenes in acetonitrile under microwave heating yield the corresponding (125)I-labelled, Cc-substituted o-carboranes with good overall radiochemical yields in short reaction times. The same synthetic strategy was successfully applied to the preparation of (131)I-labelled analogues, and further extension to other radioisotopes of iodine such as (124)I (positron emitter) or (123)I (gamma emitter) can be envisaged. Hence, the general strategy reported here is suitable for the preparation of a wide range of radiolabelled Cc-substituted o-carborane derivatives. The labelled compounds might be subsequently investigated in vivo by using nuclear imaging techniques such as Single Photon Emission Computerized Tomography or Positron Emission Tomography.

Visualisation of dual radiolabelled poly(lactide-co-glycolide) nanoparticle degradation in vivo using energy-discriminant SPECT.

The determination of nanoparticle (NP) stability and degradation in vivo is essential for the accurate evaluation of NP biodistribution in medical applications and for understanding their toxicological effects. Such determination is particularly challenging because NPs are extremely difficult to detect and quantify once distributed in a biological system. Radiolabelling with positron or gamma emitters and subsequent imaging studies using positron emission tomography (PET) or single-photon emission computerised tomography (SPECT) are some of the few valid alternatives. However, NPs that degrade or radionuclides that detach or are released from the NPs can cause artefact. Here, submicron-sized poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) stabilised with bovine serum albumin (BSA) were dual radiolabelled using gamma emitters with different energy spectra incorporated into the core and coating. To label the core, 111In-doped iron oxide NPs were encapsulated inside PLGA-NPs during NP preparation, and the BSA coating was labelled by electrophilic substitution using 125I. After intravenous administration into rats, energy-discriminant SPECT resolved each radioisotope independently. Imaging revealed different fates for the core and coating, with a fraction of the two radionuclides co-localising in the liver and lungs for long periods of time after administration, suggesting that NPs are stable in these organs. Organ harvesting followed by gamma counting corroborated the SPECT results. The general methodology reported here represents an excellent alternative for visualising the degradation process of multi-labelled NPs in vivo and can be extended to a wide range of engineered NPs.

[Nutritional support and risk factors of appearance of enterocutaneous fistulas]. / Soporte nutricional y factores de riesgo de aparición de fístulas enterocutáneas.

INTRODUCTION: Among the different factors described, nutritional support has been associated to prevention and management of enterocutaneous fistulae (ECF). OBJECTIVES: To assess the influence that the parameters related to nutritional, clinical status, and surgical variables have on the occurrence of ECF. METHODS: An observational case/control retrospective study was performed on patients admitted to the General and Digestive Surgery Department. The parameters analyzed were: diagnosis, body mass index (BMI), pathologic personal history, number of surgical interventions (SI) and complications (previous infection, bleeding, and ischemia). In patients with SI, we analyzed: number and type of SI, time until onset of nutritional support, and type of nutritional support. We performed a multiple logistic uni- and multivariate regression analysis by using the SPSSv.19.0 software. RESULTS: The primary diagnoses related to the occurrence of ECF were pancreatic pathology (OR = 5.346) and inflammatory bowel disease (IBD) (OR = 9.329). The surgical variables associated to higher prevalence of ECF emergency SI (OR = 5.79) and multiple SI (OR = 4.52). Regarding the nutritional variables, the late onset of nutrition (more than three days after SI) was associated to the occurrence of ECF (OR = 3.82). CONCLUSIONS: In surgical patients, early nutritional support , independently of the route of administration, decreases the occurrence of fistulae. Pancreatic pathology, IBD, emergency SI, and multiple SI were associated to higher prevalence of ECF. The variable hyponutrition appears as a risk factor that should be confirmed in further studies.

Positron emission tomograghy with [¹³N]ammonia evidences long-term cerebral hyperperfusion after 2h-transient focal ischemia.

BACKGROUND AND PURPOSE: It is well known that after cerebral ischemia, brain suffers blood flow changes over time that have been correlated with inflammation, angiogenesis and functional recovery processes. Nevertheless, post-ischemic spatiotemporal changes of brain perfusion have not been fully investigated to date. Here we tested whether PET with [¹³N]ammonia would evidence the perfusion changes presented by different brain regions in an experimental model of brain ischemia. EXPERIMENTAL PROCEDURES: Seven rats were subjected to a 2-h transient middle cerebral artery occlusion with reperfusion. PET studies were performed longitudinally using [¹³N]ammonia at 1, 3, 7, 14, 21 and 28 days after cerebral ischemia. RESULTS: In vivo PET imaging showed a significant increase in [¹³N]ammonia uptake at 7 days after cerebral ischemia with respect to one day after the occlusion in the cerebral territory irrigated by the MCA in both the ischemic and contralateral hemispheres. This increase was followed by a return to control values at day 28 after ischemia onset. Brain regions located both inside and outside the primary infarct areas showed similar perfusion changes after cerebral ischemia. CONCLUSIONS: [¹³N]ammonia shows hemodynamic changes after stroke involving hyperperfusion that might be related to angiogenesis and functional recovery. Long-term blood hyperperfusion is found both in ischemic and remote areas to infarction. These results may contribute to a better understanding of the evolution of cerebral ischemic lesion in animal models.

Study of hyperglycemia in non critically-ill patients receiving parenteral nutrition: incidence and risk factors.

BACKGROUND: The objectives of our study on non-critically ill patients receiving parenteral nutrition (PN) are to assess the incidence of hyperglycemia, the risk factors associated to its development and its influence in patient's evolution. METHODS: A multicentric prospective observational study was performed in 9 hospitals. Four multivariate studies were developed to study the temporal risk in the occurrence of hyperglycemia (endpoint), intensive care unit (ICU) admission, length of stay (LOS) and death. Demographics, nutrients, drugs and clinical variables were collected. Independent variables studied as a possible risk factors were: sex, diabetes mellitus 2, baseline glycemia, albuminemia, pancreatitis, surgery in the 7 days prior to the end point, infection, insulin/somatostatin/corticoids administration during the study, glomerular filtration rate (GFR), and difference in the amount of glucose administration between the endpoint and one day before. RESULTS: 119 patients were enrolled in the study, 25 cases of hyperglycemia were detected. In the clinical factors associated with PN hyperglycemia, significant variables were: surgery in the 7 days before the end point, GFR, glucose load in the 24 hours previous to the end point insulin administration and somatostatine/octreotide administration during the study. Hyperglycemia was significantly associated with ICU admission and increased LOS. CONCLUSIONS: Glucose administration in non-critically ill patients receiving PN should be reassessed downwards, especially in the immediate postsurgery, renal impairment and in patients treated with somatostatin analogues. It should be taken into account that an increase in glucose dose may lead to hyperglycemia in these patients and hyperglycemia correlates with longer hospital stay and increased frequency of ICU admissions.

Positron emission tomography with 11C-flumazenil in the rat shows preservation of binding sites during the acute phase after 2 h-transient focal ischemia.

BACKGROUND AND PURPOSE: Positron emission tomography (PET) studies in humans have used (11)C-flumazenil (FMZ) to assess neuronal viability after stroke. Here we aimed to study whether (11)C-FMZ binding was sensitive to neuronal damage in the acute phase following ischemia/reperfusion in the rat brain. EXPERIMENTAL PROCEDURES: Transient (2 h followed by reperfusion) and permanent intraluminal middle cerebral artery occlusion was carried out. (11)C-FMZ binding was studied by PET up to 24 h after the onset of ischemia. Tissue infarction was evaluated post-mortem at 24 h. Immunohistochemistry against a neuronal nuclei specific protein (NeuN) was performed to assess neuronal injury. RESULTS: No decrease in (11)C-FMZ binding was detected in the ipsilateral cortex up to 24 h post-ischemia in the model of transient occlusion despite the fact that rats developed cortical and striatal infarction, and neuronal injury was clearly apparent at this time. In contrast, (11)C-FMZ binding was significantly depressed in the ipsilateral cortex at 24 h following permanent ischemia. CONCLUSIONS: This finding evidences that (11)C-FMZ binding is not sensitive to neuronal damage on the acute phase of ischemia/reperfusion in the rat brain.

[Standard parenteral nutrition preparations and caloric adjustment]. / Preparados estándar de nutrición parenteral y ajuste calórico.

INTRODUCTION: In parenteral nutrition it is necessary to adjust the intake to the estimated caloric requirements. These needs may be achieved by the use of bi- or tricameral nutrition (EPN), although they present some rigidity regarding their composition. OBJECTIVE: To assess the adequacy of caloric intake using EPN, to determine the factors conditioning it and the associated complications. METHODS: Cohort, prospective, and observational study for 9 months in surgical patients. The calculated needs were compared with actual intake. The factors conditioning the excess and deficit (weight, age, stress factor, height, glycemia, and triglyceridemia) were studied by means of a multivariant method. The metabolic complications associated to the excess or deficit (hyperglycemias, hypertriglyceridemias) were studied by using the Student's t test. The theoretical calculations with the Harris-Benedict and the Mifflin equations were compared by lineal correlation regression. RESULTS: 94 patients were studied. In 87% of them, the caloric intake was within the +/- 15% range of the theoretical mean. Thirty patients had caloric excess, whereas 61 had deficit. Patients with high weight (> 68 kg), stress factor > 1.2, and hypertriglyceridemias (> 3 mmol/L) had higher risk for caloric deficit. Twenty two point eight percent had hyperglycemias that were correlated with caloric excess. Nineteen point eight percent had hypertriglyceridemias associated to caloric deficit. When comparing both formulas, the values correlated well except for those patients with low weight and advanced age. DISCUSSION: Although EPN fits the caloric requirements in most of the patients, in those with high weight, hypercatabolism, and hypertriglyceridemia there is a risk for caloric deficit.

Preparados estándar de nutrición parenteral y ajuste calórico / Standard parenteral nutrition preparations and caloric adjustment

Introducción: En nutrición parenteral es necesario adecuar el aporte a los requisitos calóricos estimados. Estas necesidades se podrían cubrir mediante preparados bi/tricamerales (NPE) aunque presenten rigidez en su composición. Objetivo: Evaluar la adecuación del aporte calórico al utilizar NPE, determinar los factores que la condicionan y las complicaciones asociadas. Métodos: Estudio de cohortes, observacional y prospectivo durante nueve meses en pacientes quirúrgicos. Se compararon las necesidades calculadas con el aporte real. Se estudiaron que factores condicionaban el exceso y el déficit (peso, edad, factor de estrés, altura, glucemia y trigliceridemia) mediante un modelo multivariante. Se estudiaron las complicaciones metabólicas (hiperglucemias, hipertrigliceridemias) asociadas al exceso o al déficit mediante la t de Student. Se compararon los cálculos teóricos de la ecuación de Harris-Benedict y de Mifflin mediante una regresión lineal-correlación. Resultados: Se estudiaron 94 pacientes. En el 87% el aporte calórico estaba dentro del rango ± 15% de la media teórica. 30 pacientes estuvieron en exceso calórico y 61 en déficit. Los pacientes de peso elevado (> 68 kg), factor de estrés superior a 1,2 e hipertrigliceridemias (> 3 mmol/L) tenían mayor riesgo de déficit calórico. El 22,8% presentaron hiperglucemias que se relacionaron con exceso calórico. El 19,8% presentaron hipertrigliceridemias que se asociaron con déficit calórico. En la comparación de las dos fórmulas los valores se correlacionaban excepto en pacientes con bajo peso y edad avanzada. Discusión: Aunque la NPE se adecua a los requisitos calóricos de la mayoría de los pacientes, en pacientes con elevado peso, hipercatabolismo e hipertrigliceridemia existe un riesgo de déficit (AU)

Introduction: In parenteral nutrition it is necessary to adjust the intake to the estimated caloric requirements. These needs may be achieved by the use of bi- or tricameral nutrition (EPN), although they present some rigidity regarding their composition. Objective: To assess the adequacy of caloric intake using EPN, to determine the factors conditioning it and the associated complications. Methods: Cohort, prospective, and observational study for 9 months in surgical patients. The calculated needs were compared with actual intake. The factors conditioning the excess and deficit (weight, age, stress factor, height, glycemia, and triglyceridemia) were studied by means of a multivariant method. The metabolic complications associated to the excess or deficit (hyperglycemias, hypertriglyceridemias) were studied by using the Student's t test. The theoretical calculations with the Harris-Benedict and the Mifflin equations were compared by lineal correlation regression. Results: 94 patients were studied. In 87% of them, the caloric intake was within the ± 15% range of the theoretical mean. Thirty patients had caloric excess, whereas 61 had deficit. Patients with high weight (> 68 kg), stress factor > 1.2, and hypertriglyceridemias (> 3 mmol/L) had higher risk for caloric deficit. Twenty two point eight percent had hyperglycemias that were correlated with caloric excess. Nineteen point eight percent had hypertriglyceridemias associated to caloric deficit. When comparing both formulas, the values correlated well except for those patients with low weight and advanced age. Discussion: Although EPN fits the caloric requirements in most of the patients, in those with high weight, hypercatabolism, and hypertriglyceridemia there is a risk for caloric deficit (AU)

Efficacy of enteral decontamination in the prevention of anastomotic dehiscence and pulmonary infection in esophagogastric surgery.

Our aim in this study is to evaluate the efficacy of decontamination of the high digestive tract in reducing the incidence of anastomotic dehiscence, pulmonary infection and mortality after resective gastro-esophageal surgery. A prospective randomized and double-blinded study was conducted in patients undergoing total gastrectomy for gastric cancer and esophagectomy for esophageal cancer. Two groups were studied: group A patients were given erythromycin + gentamicine + nistatine sulfate orally; group B patients were given placebo. Mortality, incidence of anastomotic dehiscence and incidence of pulmonary infection were the end points evaluated. One hundred and nine consecutive patients were randomized. Eighteen (16.5%) were excluded. From the 91 patients who were evaluated, 42 (46.2%) received an esophagectomy and 49 (53.8%) had a total gastrectomy. Esophagectomies showed: a 0% rate of anastomotic dehiscence in group A and 12.5% in group B, P = 0.176; a pulmonary infection rate of 22.2% in group A and 29.1% in group B, P = 0.443; and mortality rate was 0% in group A and 12.5% in group B, P = 0.176. After gastrectomy, anastomotic dehiscence rate was 4.5% in group A and 0% in group B, P = 0.449; pulmonary infection rate was 4.5% in group A and 11.1% in group B, P = 0.387 and mortality was 9% in group A and 0% in group B, P = 0.196. Decontamination protocol does not help in decreasing the incidence of anastomotic dehiscence, pulmonary infection and mortality in the present study. Nevertheless, there seems to be a tendency to low pulmonary infection after gastrectomy and esophagectomy and to improve the incidence of anastomotic dehiscence after esophagectomy. Further studies are needed to re-evaluate these findings.

Monitoring gene therapy by external imaging of mRNA: pilot study on murine erythropoietin.

Gene therapy is anticipated as being an important medical development. Essential to its effectiveness is the appropriate activity (protein expression) in the expected target cells. A noninvasive diagnostic procedure of successful gene expression will be of paramount importance to validate its use or its misuse (eg, sports gene doping). Externally detectable labeled oligonucleotide hybridizing with the messenger RNA generated by the transferred gene has been proposed as a possibility to monitor successful gene therapy. The authors selected the erythropoietin gene (Epo) for a pilot study on erythropoietin protein expression in mouse muscle. Oligonucleotides of peptide nucleic acid (PNA) type capable of antisense binding to unique murine Epo-mRNA sequences were synthesized by solid phase methods, and elongated at the N-terminus with the HIV Tat (48-60) cell penetrating peptide. They were labeled with fluorescence and radioactive tags to verify penetration and longer half-life properties in Epo gene transfected C2C12 mouse muscle cells as compared with corresponding wild-type cells. Downregulation of newly expressed erythropoietin protein in such cells additionally confirmed the penetration and hybridizing properties of the selected labeled oligonucleotide. I-labeled Tat-PNAs were intravenously injected into mice that had previously received the Epo gene into the right tibialis muscle by DNA electrotransfer. Preferential accumulation of radioactivity in the transferred limb as compared with the contralateral limb was ascertained, especially for I-Tat-CTA CGT AGA CCA CT (labeled Tat-PNA 1). This study provides experimental data to support the potential use of external noninvasive image detection to monitor gene therapy. The extension of the approach to more sensitive methods for whole-body external detection such as positron emission tomography appears feasible.

[Multicenter study on the prevalence of hyperglycemia among hospitalized patients with parenteral nutrition]. / Estudio multicéntrico de prevalencia de hiperglucemia en pacientes hospitalizados con nutrición parenteral.

OBJECTIVE: The aim of this cross-sectional national multicentric study was to determine the prevalence of hyperglycemia in patients with parenteral nutrition and to assess other clinical factors associated with this complication. METHOD: All Spanish hospital pharmacy services were invited to participate in the study. RESULTS: Twenty eight (28) pharmacy services agreed to participate. The study included 442 patients. The prevalence of hyperglycemia (plasma levels > 200 mg/dL) was 26.7%. Eighty four point two per cent of the patients received less than 3.5 mg/kg/minute of glucose, this infusion rate being considered as the safe threshold. In most patients, follow-up of glycemia was based on capillary blood determination with reactive strips and in 27.6% of the cases in which insulin was prescribed, it was added to the parenteral nutrition bag, in full or in part. No significant correlations were found between glycemia and the clinical factors studied (disorders, fever, medication), except for insulin. CONCLUSIONS: This national multicentric study of the prevalence of hyperglycemia among patients with parenteral nutrition, leaded by hospital pharmacists, was a joint effort aimed to better understand this metabolic complication. Findings are consistent with those reported by other authors and have allowed us to describe the current situation.

Triglicéridos y nutrición parenteral / Triglycerides and parenteral nutrition

Una de las complicaciones metabólicas que se asocia con relativa frecuencia con la nutrición parenteral es la hipertrigliceridemia. Su etiología se relaciona con la alteración del aclaramiento plasmático de los lípidos, bien por una disminución de la actividad de la lipoproteinlipasa, bien por un aporte excesivo. Durante la utilización de la nutrición parenteral es importante conocer el umbral de triglicéridos plasmáticos a partir del cual la administración de lípidos exógenos es ineficiente desde el punto de vista metabólico o está asociado a sobrecarga grasa. Hay diversas situaciones clínicas como la sepsis, la insuficiencia renal, la pancreatitis, así como determinados fármacos, como glucocorticoides o ciclosporina, que se asocian con hipertrigliceridemia. En estos casos, cuando se instaura una pauta de nutrición parenteral, el riesgo de desarrollar hipertrigliceridemia es especialmente elevado. En el presente trabajo se revisan las distintas causas que pueden relacionarse con hipertrigliceridemia y que pueden suponer un factor de riesgo en pacientes con nutrición parenteral (AU)

Hypertriglyceridemia is a metabolic disorder frequently correlated with the use of parenteral nutrition. The etiology of hypertriglyceridemia in patients undergoing parenteral nutrition is associated with alterations in plasma lipid clearance due to an excessive supply or to a decrease in lipoprotein lipase activity. During parenteral nutrition therapy, it is important to determine the threshold plasma triglyceride level above which exogenous lipids cannot be efficiently metabolized or would be associated with lipid overload. Several clinical and metabolic situations have been related to hypertriglyceridemia, such as sepsis, renal failure, pancreatitis and the use of certain drugs such as glucocorticoids and cyclosporine. In these cases, parenteral nutrition increases the risk of developing hypertriglyceridemia. In the present article, we review some of the risk factors for hypertriglyceridemia in patients with parenteral nutrition (AU)

Use of colistin in the treatment of multiple-drug-resistant gram-negative infections.

PURPOSE: The use of colistin for the treatment of infections caused by multiple-drug-resistant (MDR) gram-negative microorganisms was studied. METHODS: The efficacy of colistin for treating infections caused by MDR gram-negative microorganisms and the development of renal toxicity were studied in hospitalized adult patients in Spain. Patients treated between January 2001 and October 2001 were included. RESULTS: Over the study period, 71 courses of inhaled colistin, 12 courses of i.v. or intramuscular (i.m.) colistin, and 2 courses of intrathecal colistin were administered to 80 patients. All were infected by MDR organisms: 69 (86%) by Acinetobacter baumannii and 11 (14%) by Pseudomonas aeruginosa. In 41 patients (51%), the episodes were caused by A. baumannii strains susceptible exclusively to colistin. The causative organisms were cleared in 92% of the patients from whom posttreatment repeat specimens were obtained. The in-hospital mortality rate was 18% (14 patients). There were no significant changes in mean serum urea or creatinine concentrations in patients receiving i.v. or i.m. therapy. CONCLUSION: Colistin was used in 80 patients infected with A. baumannii or P. aeruginosa and appeared to be efficacious and safe.

[Current controversies in pathophysiology of cervical spondylotic myelopathy]. / Controversias en la fisiopatología de la mielopatía cervical espondilótica.

Cervical spondylotic myelopathy is the most severe consequence of degenerative disease of cervical spine. In this article we perform a bibliographic review, addressing current controversies in its pathophysiology. Present work lines of most groups dedicated to the study of this condition are focused on improving surgical techniques designed for the treatment of this disease. Pathophysiological studies are scarce, and most of our pathophysiological knowledge of cervical spondylotic myelopathy is based in works done in 60s and 70s. Literature of the last decade lacks neurochemichal studies parallel to those existing for acute spinal injury. In the same way, only three prospective clinical trials comparing conservative and surgical treatment have been done, and none of them has demonstrated clear superiority of surgery. Given the high prevalence of this disease, the need for deep knowledge of its pathophysiologic, neurochemichal and molecular basis, and the optimization of surgical treatment is justified. This probably implies the need for prospective randomized trials to determine which patients are going to benefit from surgery.

The importance of clinical factors in parenteral nutrition-associated hypertriglyceridemia.

AIMS: The purpose of this study was to establish the relevance of several clinical factors associated with parenteral nutrition (PN) hypertriglyceridemia and to construct a predictive model for this complication. METHOD: This multicenter study included all patients with initial serum triglyceridemia <3 mmol and receiving a minimum of 7 days' PN therapy. The study ended for each patient when hypertriglyceridemia developed or PN was terminated. Two multivariate models were constructed, one to study the clinical factors and the second to predict plasma triglyceridemia. A total of 22 clinical factors studied as independent variables were included in the multiple-step regression models only when they showed a P-value over 0.1. Statistical significance was determined by the confidence interval of the odds ratio (OR) and the partial regression coefficient (b). RESULTS: The study included 260 patients from 14 hospitals. Lipid administration was 0.83+/-0.37 g/kg/day. Among the total, 68 patients (26.2%) showed hypertriglyceridemia. Variables included in both models were serum glucose (OR, 2.63; b, 0.06), renal failure (OR, 10.56; b, 1.70), corticoid administration >0.5 mg/kg (OR, 7.98; b, 0.97), pancreatitis (OR, 4.38; b, 0.64), sepsis (OR, 4.48; b, 0.24), lipids infused (OR, 3.03; b, 0.24) and heparin administration >3 mg/kg/day (OR, 0.11; b, -1.21). CONCLUSION: Although the rate of lipid infusion was low, certain clinical factors modified triglyceridemia. Nevertheless, relatively fast plasma clearance of lipids infused indicates that a reduction in lipid supply could be a quick, effective measure for controlling hypertriglyceridemia. Thus, careful monitoring of patients with clinical factors predicting risk in the model studied, with adjustment of lipid perfusion rates accordingly, is suggested to avoid hypertriglyceridemia.