Biomedical subjects
Publications and source records attributed to X Guirao.
Cancer cachexia is a complex syndrome which occurs in more than two-thirds of patients who die with advanced cancer. The main components of this pathological state are anorexia and metabolic abnormalities such as glucose intolerance, fat depletion, and muscle protein catabolism among others. The aim of the present study is to review the different therapeutic approaches that have been designed to fight and counteract cancer cachexia.
BACKGROUND: The empiric antibiotic treatment of intraabdominal infections is in constant evolution. Monotherapy appears to be a desirable goal because of the simplicity of its administration, lack of toxic effects and wide spectrum. PATIENTS AND METHODS: A multicentre, prospective, randomized, open study was carried out to compare two antibiotic regimens in the treatment of intraabdominal infections in patients undergoing surgery. Ninety-eight consecutive patients were randomly allocated into two groups. One group (GM, n = 51) received meropenem (1 g/8 h) and the other (GCM, n = 47) a combination of cefotaxime (2 g/8 h) plus metronidazol (0.5 g/8 h). Clinical and bacteriological responses were assessed at the end of treatment and at 2-4 weeks. RESULTS: The severity of patients as assessed by the APACHE II score was similar in both groups (GM: 7.2 and GCM: 8.1). Three patients in each group could not be evaluated due to premature interruption of treatment or deviation from the protocol. The mean duration of treatment was 7.4 days in GM and 7.9 days in GCM. A satisfactory clinical response was obtained in 95% of patients in both groups. 31 patients (61%) in GM and 26 patients (55%) in GCM were bacteriologically evaluable. Bacteriological erradication was achieved in 94% of patients in GM and in 92% of patients in GCM. CONCLUSION: Meropenem is a good alternative for single antibiotic therapy in intraabdominal infections of moderate severity.
Preoperative parenteral nutrition (PPN) may be beneficial for severely malnourished patients who are candidates for a major elective surgical procedure. The response to PPN, however, has not been thoroughly investigated. Expansion of the extracellular water compartment may occur in some patients, producing a further decrease in the serum albumin concentration and increasing the postoperative complications. Our aims were to investigate the occurrence of and factors associated with water and sodium retention during PPN and its impact on postoperative respiratory complications. Forty-one patients with gastrointestinal cancer and severe malnutrition (weight loss > 15% and/or serum albumin < 35 g/L) were randomly allocated to two groups receiving isocaloric isonitrogenous PPN for 10 d. The Standard PPN Group (SG, n = 19) received 70% of nonprotein calories as glucose, 45 cc of water.kg-1.d-1, and 140 mEq/d of sodium chloride; and the Modified Group (MG, n = 22) received 70% of calories as fat, 30 cc of water.kg-1.d-1, and no sodium. Weight and albumin changes, diuresis, sodium and water balances, and postoperative complications were recorded. At the end of PPN, the SG showed a higher weight gain (0.8 versus -1.5 kg, P = 0.0001) and albumin decrease (-0.7 versus 2.3 g/L, P = 0.006). Diuresis and sodium balance were greater in the SG (1,230 versus 959 mL/d, P = 0.003 and 40 versus -27 mEq/d, P = 0.001). Weight changes correlated with water (r2 = 0.46, P = 0.001) and sodium (r2 = 0.62, P = 0.0001) balances. Inappropriate responses to PPN in both groups (expansion or depletion of the extracellular water compartment) were associated with a significant increase in pulmonary postoperative complications. During PPN, extracellular water expansion--as determined by increasing weight and lowering of the serum albumin concentration--and aggressive fluid therapy to treat water and sodium depletion seem crucial to the development of postoperative respiratory complications.
Induction of pneumonia in C57Bl/6 mice by intranasal inoculation with 10(6) cfu of Streptococcus pneumoniae resulted in sustained expression of interleukin (IL)-6 mRNA in lungs and increases in lung and plasma IL-6 concentrations. In IL-6-deficient (IL-6-/-) mice, pneumonia was associated with higher lung levels of the proinflammatory cytokines tumor necrosis factor-alpha, IL-1beta, and interferon-gamma and of the antiinflammatory cytokine IL-10 than in wild type (IL-6+/+) mice (all P < .05). Also, the plasma concentrations of soluble tumor necrosis factor receptors were higher in IL-6-/- mice (P < .05), while the acute-phase protein response was strongly attenuated (P < .01). Lungs harvested from IL-6-/- mice 40 h after inoculation contained more S. pneumoniae colonies (P < .05). IL-6-/- mice died significantly earlier from pneumococcal pneumonia than did IL-6+/+ mice (P < .05). During pneumococcal pneumonia, IL-6 down-regulates the activation of the cytokine network in the lung and contributes to host defense.
Postinjury deficits in monocyte tumor necrosis factor receptors (moTNFR) activity may alter beneficial functions during an inflammatory response. Several counter-regulatory hormones elicited during inflammation may modulate tumor necrosis factor (TNF) activity, but little is known about their influence on moTNFR. Also, catecholamines inhibit TNF production, but the adrenoreceptor mechanism of this effect has not been fully clarified. To determine the effect of catecholamines and corticosteroids on moTNFR, whole blood was coincubated for up to 8 (moTNFR) or 24 h (cytokines) in the presence of lipopolysaccharide (100 ng/ml) and 1) epinephrine (Epi, 10(-6) M), dexamethasone (Dex, 10(-6) M) or both (EpiDex, 10(-6) M) to assess the expression of total moTNFR, moTNFR-I, and moTNFR-II. 2) Epi and norepinephrine (EpiNE, 10(-6) M) and the alpha 1 + 2-, beta 1 + 2-, beta 1-, or beta 2-adrenergic antagonists were used to assess the role of such adrenoreceptors on total moTNFR and TNF production, and N6,2'-O-dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) alone or in combination with the phosphodiesterase inhibitor Ro-20-1724/000, to study the cAMP-dependent pathway on total moTNFR. We found that Epi upregulated total moTNFR and moTNFR-II. Dex did not significantly influence total moTNFR or moTNFR-II. Also, EpiNE increased total moTNFR and inhibited TNF by a beta 2-dependent mechanism. DBcAMP (10(-5) M) modestly enhanced total moTNFR. This suggests a common mechanism for acutely enhancing moTNFR and attenuation of soluble TNF appearance during conditions of severe stress.
A generalized host inflammatory response is necessary to orchestrate the maintenance or recovery of tissue repair and immune competence following severe injury or infection. When excessive in initial magnitude or duration, however, these otherwise beneficial inflammatory processes may eventuate in deterioration rather than restoration of homeostasis. Although the adverse consequences of excessive inflammatory stimuli may be acutely evident, their influences are more often insidious. A complex cascade of endogenously derived proinflammatory mediators are currently hypothesized to be responsible for both the beneficial and the adverse sequelae of infection and injury. The cytokine proteins tumor necrosis factor and interleukin 1 have been most widely studied as potential targets for antagonist intervention in both experimental models and prospective clinical trials. Preclinical evidence supporting these approaches is briefly discussed herein, as are the results of clinical trials attempting to modulate cytokine influences in the presence of sepsis. The present discussion focuses on potential insights gained from these investigations and the evolving appreciation for the importance of cytokine counterregulatory mechanisms. Examples of potentially complex interactions between inflammatory cytokines and infection-induced antagonist proteins or counterregulatory hormones are provided. It is hypothesized that a sustained imbalance among these proinflammatory and counterregulatory influences may be a critical determinant of outcome in patients with severe infection.
The present study was set up to develop a new model of intraabdominal abscess (IAA) useful for hydrosaline metabolism studies based on the ligation of the appendix (AL) and wrapping of the appendix tip with omentum. Two experiments were designed: (1) to characterize the model and (2) to investigate extracellular volume (ECV) changes during parenteral nutrition (PN). Four groups of rabbits were studied at 3 (3DA) and 7 days (7DA) after AL or sham operation. PN was given for 6 days to two groups of septic rabbits: high volume HV) and low volume (LV) groups received 100 and 70 ml/kg.day of water with 7 and 0 meq/day of ClNa, respectively. Serum albumin (SA), ECV, and weight, water and sodium balances were determined. In 3DA, weight loss, reduced spontaneous intake, negative water balance, and reduction in SA were noted. Low SA, higher weight loss, and reduced intake were still observed in 7DA. SA correlated with ECV (r2 = 0.61, P = 0.003) in 7DA. Positive nitrogen balance was achieved during PN. The HV group had higher water and sodium balances than LV. In the HV group only, SA negatively correlated with sodium balance and with ECV at the end of PN (r2 = 0.87, P = 0.0007 and r2 = 0.9, P = 0.0001). The impact on hydrosaline metabolism of IAA in this model resembles that of moderate sepsis in humans. SA decrease appears to have two major components: escape around the inflammatory area and dilution. ECV expansion after PN is influenced by the initial SA concentration.
The present study was designed to investigate whether calorie source influences sodium and water metabolism and sympathetic activity during parenteral nutrition (PN). 20 New Zealand rabbits were starved until a mean weight loss of 18% was achieved and then re-fed for 6 days with 2 formulae of PN with different glucose-fat proportions. In the Glucose group (n = 9), 70% of non-protein calories were given as glucose while in the Lipid group (n = 11), 70% of non-protein calories were administered as lipids. Rabbits with a high glucose intake showed significantly higher weight gain (151 +/- 87 vs. 52 +/- 7 g, P = 0.01), water cumulative balance (542 +/- 132 vs. 411 +/- 87 ml; P = 0.02) and urinary metanephrine excretion (0.42 +/- 0.12 vs. 0.30 +/- 0.1 mumol/d, P = .03). Only in this group, urinary metanephrines correlated positively with water and sodium balances (r2 = 0.6; P = 0.02 and r2 = 0.7; P = 0.009 respectively). The Glucose group showed 2 different responses and in a second experiment 10 additional rabbits were added to this group to allow a statistical analysis of the response pattern: half of the animals increased their extracellular water (ECW) compartment while the remaining animals did not. The former group had higher sodium balance (13.9 +/- 8 vs. 4.3 +/- 5; P = 0.004) and wet lung weight (8.9 +/- 0.9 vs. 7.9 +/- 0.8; P < 0.05) after re-feeding and, at the beginning of PN, their serum aldosterone concentration were also higher (221 +/- 11 vs. 130 +/- 47 pmol/l; P < 0.05). In conclusion, glucose based PN appears to increase sympathetic activity and induce spurious weight gain due to markedly positive wate and sodium balances. Plasma aldosterone concentration at the end of starvation period influences sodium retention and ECW expansion during high glucose re-feeding.
59 patients with suspected central venous catheter related bacteraemia (CRB), while receiving parenteral nutrition, were studied prospectively. 41 (Group 1) were managed conservatively: cultures were taken from the catheter hub lumen, skin at the catheter entry site and peripheral blood; the catheter was then heparinised and locked for 24-48 h. The catheter was withdrawn only if cultures were positive; otherwise parenteral nutrition was resumed. In 18 patients the catheter was immediately withdrawn (Group 2) and the same cultures plus tip culture were performed. 13 patients of Group 1 with positive hub or skin cultures, had their catheters removed and 12 had blood cultures matching for the same micro-organism. Negative skin and hub cultures had a negative predictive value for CRB of 96%. A positive hub culture had a 100% positive predictive value for CRB. CRB was diagnosed in 11 patients out of the 18 in whom catheters were withdrawn immediately (Group 2). Thus, 1 out of 41 catheters and 7 out of 18 catheters were removed unnecessarily in Groups 1 and 2 respectively (p = 0.001, Fisher's test). In all, 24 CRBs were documented and 15 were due to coagulase negative staphylococci. The catheter hub was the commonest origin of CRB followed by the infusate and the skin. In febrile patients on parenteral nutrition, negative skin and hub cultures accurately predict or rule out CRB and should be used more often to avoid withdrawal of sterile catheters.
Pharmacological treatment of patients with enterocutaneous fistulas aims at reducing output, increasing the chance of spontaneous closure and reducing the time of fistula closure. Our initial experience with octreotide suggests that this drug effectively reduces output of established enterocutaneous fistulas when compared with a placebo in patients on parenteral nutrition. Output reduction was independent of the basal output. Likewise, this somatostatin analogue was shown to accelerate fistula closure in a series of 27 patients treated with the drug after having received parenteral nutrition for a mean of 25 days. When compared with a historical series, the rate of spontaneous fistula closure was not modified by octreotide.
Life emerged on our planet from a fluid environment which probably contained a similar concentration of sodium and other electrolytes to that of the extracellular fluid of mammals (1). The maintenance of the volume and composition (homeostasis) of this internal fluid surrounding all the body cells is essential for survival. Malnutrition and illness are associated with alterations in the distribution and in the renal handling of water and sodium within the body (2). Thus, an understanding of water and salt physiology is essential for the proper practice of nutritional support.
34 New Zealand rabbits were starved until a mean weight loss of 15% to 20% was achieved and then were parenterally re-fed with four different total parenteral nutrition (TPN) formulae for 6 days. Regimens were isocaloric (85 kcal/kg/day) and isonitrogenous (0.52 gN/kg/day) with the following formulae: group S-GLU-70 (water 100 ml/kg/day, Na 7 mEq/day and 70 30 % of calories as glucose/lipids, n = 9), group S-GLU-50 (water 100 ml/kg/day, Na 7 mEq/day and 50 50 % of calories as glucose/lipids, n = 9), group L-GLU-30 (water 70 ml/kg/day, no sodium and 30 70 % of calories as glucose/lipids, n = 8) and group L-GLU-50 (water 70 ml/kg/day, no sodium and 50 50 % of calories as glucose/lipids, n = 8). The group S-GLU-70 showed the highest water and sodium balances (p = 0.001 respectively, ANOVA test). Group S-GLU-70 showed also a greater weight gain (p = 0.0001) and, although not statistically significant, the lowest albumin at the end of the TPN. Glucose load appears to be responsible for the rapid weight gain and positive water and sodium balances during TPN in depleted non-stressed animals.
Twenty-three New Zealand rabbits were starved until a mean weight loss of 21% was achieved and then re-fed parenterally with two different total parenteral nutrition (TPN) formulae: a standard formula (Group SF, n = 12) containing 100 ml/kg/day of water, 7 mEq/day of sodium and 70% of non-protein calories as glucose; and a modified formula (Group MF, n = 11) containing 70 ml/kg/day of water, no sodium and 70% of non-protein calories as fat. After 6 days of parenteral nutrition, Group SF showed a higher weight gain than Group MF (10 +/- 5.8% vs. 1.4 +/- 5%; p = 0.001) and serum albumin concentration in Group SF was lower than in Group MF (25.9 +/- 4.2 vs. 32 +/- 4.5 g/l; p = 0.004). There was a close correlation between weight gain and water and sodium balances (r(2) = 0.714; p = 0.0001 and r(2) = 0.447; p = 0.0005, respectively). In Group SF, a close correlation was found between the free water clearance and water balance (r(2) = 0.711, p = 0.0006). In conclusion, in Group MF water and sodium restriction led to a better nutritional response in terms of improving serum albumin concentrations and minimising weight gain, probably due to less expansion of the extracellular fluid compartment in this group.
ECW, and particularly its interstitial component, expands easily with malnutrition, sepsis, and trauma and after aggressive intravenous fluid therapy. In this scenario, hypoalbuminemia is usually the result of both an increased capillary escape rate due to leaky endothelium and increased distribution volume; this can be worsened by artificial intravenous nutrition with sodium, water, and glucose. Monitoring ECW is essential during TPN. Short-term changes in weight and serum albumin concentration are helpful to control ECW volume and prevent ECW expansion. Tetrapolar bioimpedance analysis is a promising technique for accurate bedside measurement of changes in body fluid compartments.