More Evidence that Depressive Symptoms Predict Mortality in COPD Patients: Is Type D Personality an Alternative Explanation?

Background/Purpose  

The present study attempted to replicate our previous finding that depressive symptoms are a risk factor for mortality in stable chronic obstructive pulmonary disease (COPD), but in a different population with a different measure of depressive symptoms. We further investigated whether type D personality is associated with mortality in patients with COPD and whether it explains any relationship observed between depressive symptoms and mortality.     

The current status of sentinel lymph node staging in rectal cancer

The sentinel lymph node (SLN) procedure in rectal cancer was studied according to the following parameters: identification rate, accuracy, sensitivity, false-negative rate, and upstaging percentages. The analyzed studies reported a large variation of nodal identification rates with overall high false-negative rates (ie, the percentage of rectal cancer patients in whom the SLN did not correctly represent the tumor status of the lymph node basin). These results are likely due to the anatomic localization of the rectum and disturbed lymphatic drainage after preoperative radiotherapy with or without concurrent chemotherapy. Therefore, the SLN procedure does not appear to be technically feasible in rectal cancer, and full lymphatic staging (as part of total mesorectal excision) should remain the standard for patient care.     

L-arginine supplementation in hyperdynamic endotoxemic pigs: effect on nitric oxide synthesis by the different organs

OBJECTIVES: Under septic conditions, the protective role of nitric oxide in the organs may become compromised at a time of increased demand as a result of decreased availability of L-arginine. It remains unknown whether supplementation with L-arginine, as a substrate, can modulate organ nitric oxide production. DESIGN: Controlled study with laboratory animals. SETTING: University research laboratory. SUBJECTS: Female crossbred pigs. INTERVENTION: Pigs were challenged with Escherichia coli endotoxin (intravenously) and received intravenous fluid resuscitation for 24 hrs to reproduce a model of long-lasting hyperdynamic endotoxemia. Pigs were infused with either L-arginine or L-alanine intravenously during endotoxin and via the intragastric route after cessation of endotoxin infusion. The effects of L-arginine supplementation on nitric oxide synthesis and the relationships with arginine metabolism were determined with a stable isotope infusion protocol. Also, organ nitrite plus nitrate fluxes were measured. Implantation of multiple catheters enabled in vivo measurements across the hindquarter muscle, the portal-drained viscera, the liver, and the kidneys. MEASUREMENTS AND RESULTS: The isotope conversion method showed that L-arginine intervention significantly increased nitric oxide production by the portal-drained viscera, liver, and kidneys, resulting in elevated whole-body nitric oxide synthesis under endotoxemic and postendotoxemic conditions. Organ nitrite plus nitrate fluxes only tended to increase because of high variance among data. CONCLUSIONS: In this endotoxemia model, supplemental use of L-arginine favored nitric oxide synthesis in various organs.     

The objective burden in partners of heart failure patients; development and initial validation of the Dutch Objective Burden Inventory.

BACKGROUND: Measures on objective caregiver burden in partners of Heart Failure patients are hardly available and never include HF specific aspects. AIM: The main objective of our study was to develop an inventory that assesses the objective caregiver burden of partners of HF patients, including the full range of potential care giving demands. METHODS: To develop the inventory, six domains of caregiving demands were identified. Items for the domains were generated from the literature, expert opinion and existing scales. The original 50-items self-report inventory was administered to 321 partners of HF patients. Demographic data of HF partners were collected by questionnaire. Clinical data of the HF patients were collected by chart review. RESULTS: Component analysis led to exclusion of 12 original items and to a meaningful four-factor solution with a total explained variance of 43%. The components reflected four different kinds of care giving tasks; personal care, emotional, motivational and practical (treatment related) support. They demonstrated good internal consistency and initial validity was supported by a pattern of meaningful associations with external variables. CONCLUSION: The Objective Burden Inventory is a promising inventory to assess objective care giving tasks performed by HF partners, including emotional and motivational support. It provides information on the caregiver situation that may help to develop effective interventions.     

Nutrition in patients with acute pancreatitis

Acute pancreatitis is a disease with varying severity. Patients with the mild form do not require nutritional support because oral intake is resumed rapidly. Studies on nutritional support in acute pancreatitis have included patients with both mild and severe disease. In this heterogeneous group, total parenteral nutrition did not improve outcome compared with no nutrition at all. This is caused in part by an increase in septic complications during total parenteral nutrition. Likewise, no benefit from enteral nutrition was observed compared with no nutrition, probably because the group was heterogeneous or because nutritional goals were not achieved. Patients with severe acute pancreatitis become profoundly catabolic. This group undoubtedly requires nutritional support to treat undernutrition. The limited available data indicate that enteral nutrition, if well tolerated, is superior to parenteral nutrition for patients with severe acute pancreatitis. Based on current knowledge, a combination of early total parenteral nutrition and enteral nutrition is advisable as soon as enteral nutrition is tolerated. Monitoring of gut function is crucial in this situation.     

Use of intra‐articular carbon dioxide and air for MR arthrography: a feasibility study

During animal experiments, carbon dioxide (CO₂) and air were used as a novel contrast agent for direct magnetic resonance arthrography (MRAr). MRAr was performed after injection of CO₂ and air in the knee joints of two pigs. MR images of phantoms containing air, CO₂ and nitrogen were compared. After intra‐articular injection, both present as a signal void on various sequences and permit sharp delineation of cartilage and other adjacent structures. Despite the potential for artefact generation, only a slight susceptibility artefact was seen after injection of CO₂ and air. In phantom experiments, air, CO₂ and nitrogen demonstrated identical slight regular susceptibility artefacts at the phantom margins. CO₂ MRAr can yield high contrast between cartilage, ligaments and synovium relative to the joint compartment. Therefore, this technique might be useful as an investigational method for the evaluation of cartilage surface lesions and possibly as an alternative contrast agent for clinical use. Copyright © 2006 John Wiley & Sons, Ltd.     

Hypoalbuminemia: Pathogenesis and Clinical Significance

Hypoalbuminemia is associated with inflammation. Despite being addressed repeatedly in the literature, there is still confusion regarding its pathogenesis and clinical significance. Inflammation increases capillary permeability and escape of serum albumin, leading to expansion of interstitial space and increasing the distribution volume of albumin. The half‐life of albumin has been shown to shorten, decreasing total albumin mass. These 2 factors lead to hypoalbuminemia despite increased fractional synthesis rates in plasma. Hypoalbuminemia, therefore, results from and reflects the inflammatory state, which interferes with adequate responses to events like surgery or chemotherapy, and is associated with poor quality of life and reduced longevity. Increasing or decreasing serum albumin levels are adequate indicators, respectively, of improvement or deterioration of the clinical state. In the interstitium, albumin acts as the main extracellular scavenger, antioxidative agent, and as supplier of amino acids for cell and matrix synthesis. Albumin infusion has not been shown to diminish fluid requirements, infection rates, and mortality in the intensive care unit, which may imply that there is no body deficit or that the quality of albumin “from the shelf” is unsuitable to play scavenging and antioxidative roles. Management of hypoalbuminaemia should be based on correcting the causes of ongoing inflammation rather than infusion of albumin. After the age of 30 years, muscle mass and function slowly decrease, but this loss is accelerated by comorbidity and associated with decreasing serum albumin levels. Nutrition support cannot fully prevent, but slows down, this chain of events, especially when combined with physical exercise.     

Endothelial cells internalize and degrade RGD-modified proteins developed for tumor vasculature targeting.

Tumor vasculature can be targeted by peptides containing an RGD (Arg-Gly-Asp) sequence, which bind to alpha(v)beta3 and alpha(v)beta5 integrins on angiogenic endothelial cells. By covalently attaching cyclic RGD-peptides (cRGDfK) to a protein backbone, we prepared a multivalent peptide-protein conjugate with increased affinity for alpha(v)beta3/alpha(v)beta5 integrins. We demonstrated that RGDpep-protein conjugate bound to HUVEC, whereas the conjugate prepared with the control RAD peptide was devoid of any binding. RGDpep-protein conjugate was furthermore functional in inhibiting the adhesion of HUVEC to alpha(v)beta3/alpha(v)beta5 ligand vitronectin, and direct binding of the radiolabeled conjugate to HUVEC was inhibited by alpha(v)beta(3)/alpha(v)beta5-specific RGD peptides. Finally, RGDpep-protein conjugate was shown to be internalized and degraded by HUVEC, a process that could be inhibited by lysosomal degradation inhibitors chloroquine and ammonium chloride. This cellular handling was significantly influenced by the presence of cations, which strongly inhibited internalization. This is the first study that shows direct evidence that primary endothelial cells are capable of internalizing RGD-containing macromolecular proteins. This feature makes them attractive carriers for the intracellular delivery of potent anti-angiogenic drugs into endothelial cells for the treatment of cancer and chronic inflammatory diseases.