Distribution of micafungin in the tissue fluids of patients with invasive fungal infections

The distribution of micafungin (MCFG) in tissue fluids, such as cerebrospinal fluid (CSF), pleural effusions, ascites, and wound tissue fluids, was examined in seven patients with invasive fungal infections. MCFG (100–300 mg) was administered once daily over a 1-h intravenous infusion. Blood and tissue fluid samples were collected from 1 to 24 h after infusion. Although two patients had similar MCFG concentrations in their plasma, the concentrations in the CSF differed between these two patients. The concentration in the CSF of one patient was much higher than the MIC₉₀ for Candida albicans, Candida glabrata, and Aspergillus fumigatus, whereas the MCFG concentration in the CSF of the other patient was comparable to the MIC₉₀. By contrast, MCFG concentrations in pleural effusions, ascites, and wound tissue fluids were above the MIC₉₀ . These results suggest that intravenous MCFG may be effective to treat invasive fungal infections that invade the organs and tissues.     

Effect of fluid collections on long-term outcome after lower limb amputation

Singh R, Venkateshwara G. Effect of fluid collections on long-term outcome after lower limb amputation.ObjectiveTo ascertain the long-term outcome for individuals found to have fluid collections in residual limbs after amputation.DesignProspective cohort study.SettingOutpatient follow-up at a prosthetic rehabilitation unit.ParticipantsSuccessive lower limb amputations (N=105) scanned for fluid collections after operation and followed up after 3 years.InterventionsNot applicable.Main Outcome MeasuresSurvival; secondary outcomes of prosthetic limb use, hours of prosthetic limb-wearing, anxiety and depression levels.ResultsAfter 3 years, 70 individuals were alive, of whom 21 (30%) had fluid collections originally. There was no significant difference at follow-up between the group that had fluid collections in their residual limbs after surgery and the group that did not in terms of survival (χ²₁=.21, P=.64), numbers wearing prosthetic limb (χ²₁=.102, P=.75), hours of limb wearing (t₃₇=.35, P=.72), anxiety (χ²₁=.77, P=.78), and depression (χ²₁=1.98, P=.16). A multivariable logistic regression confirmed that presence of fluid collection was not associated with survival.ConclusionsFluid collections in residual limbs after amputation are common, but patients can be reassured that their long-term outcomes are not affected.     

Human fluids alter DNA-acquisition in Acinetobacter baumannii

Transformation is one of the mechanisms of acquisition of foreign genetic material leading to the emergence of multidrug resistant (MDR) bacteria. Recently, human serum albumin (HSA) was shown to specifically increase transformation frequency in the nosocomial pathogen Acinetobacter baumannii. To further assess the relevance of HSA as a possible modulator of A. baumannii transformation in host-pathogen interactions, in this work we examined the effect of different human fluids. We observed a significant increase in transformation frequencies in the presence of pleural fluid, whole blood cells and liquid ascites, and to a lesser extent with urine. The observed effects correlate with both HSA and bacterial content found in the assayed patient fluids. Taken together, these results are in agreement with our previous findings that highlight HSA as a possible host signal with the ability to trigger natural transformation in A. baumannii.     

Protein metabolism and exchange as influenced by constriction of the vena cava; experimental ascites as internal plasmapheresis; sodium chloride and protein intake predominant factors

Constriction of inferior vena cava above the diaphragm is used to produce experimental ascites in the dog. This type of experimental ascites drains the body protein reserves, reduces the level of circulating plasma proteins, and in effect is an internal plasmapheresis. As the ascitic fluid is withdrawn and the proteins measured, we observe a production of ascitic protein (80–90 gm. per week) comparable to that removed by plasmapheresis (bleeding and replacement of red cells in saline). High protein diet tends to decrease the ascites but the protein content of the ascitic fluid may increase. Sodium chloride increases notably the volume of the ascites which accumulates and the total ascitic protein output increases. Sodium-free salt mixtures have a negative influence. High protein diet low in sodium salts gives minimal ascitic accumulation under these conditions. The question of circulation of the ascitic fluid is raised—how rapid is the absorption and the related accumulation?     

STUDIES IN EDEMA : I. COMPARATIVE INVESTIGATION INTO THE ACTION OF CALCIUM CHLORIDE AND SODIUM CHLORIDE ON THE PRODUCTION OF URINE,INTESTINAL FLUID AND ASCITES.

1. The secretion of urine and the elimination of fluid through the intestinal canal which are caused by the intravenous injection of solution of 0.85 per cent. sodium chloride are decreased by the addition of calcium chloride to the sodium chloride solution. The secretion of urine is more markedly inhibited than is the elimination of fluid through the intestines. 2. In contradistinction to the decreased elimination of fluid through the kidneys and intestines, addition of calcium chloride to the sodium chloride solution increases markedly the transudation of fluid into the peritoneal cavity. To a certain degree the urine and ascites may be said to increase in an inverse proportion. 3. Although calcium chloride inhibits both absorption from and secretion into the intestines it seems to decrease the secretion more markedly than the absorption. 4. The action of calcium chloride in increasing the ascitic fluid is a double one: first, by diminishing the amount of urine secreted: secondly, by increasing the ascites independently of its action on the kidneys. The latter may be a direct action on the endothelial cells of the peritoneal cavity: this, however, must be determined by further investigations. 5. Addition of calcium chloride to the infused fluids increases the tendency to the occurrence of edema of the lungs. 6. Infusion of large quantities of fluid into animals dilutes the blood, but this dilution seems to be carried only to a certain degree— about 30 per cent.—and to be independent of the chemical character of the solution and of the function of the kidneys. 7. The presence or absence of the kidneys has a marked influence on the intestinal and ascitic fluids. When the averages of ascitic and intestinal fluids per 1,000 c.c. of retained fluid in non-nephrectomized animals and these fluids per 1,000 c.c. of infused fluid in nephrectomized animals are compared, more fluid is found in the case of the nephrectomized animals. This fact can only be explained in part by the shorter time necessary for the same amount of fluid to be retained in the case of the nephrectomized animals. Nephrectomy causes an increase of the ascites and the intestinal fluids through a mechanism which will have to be investigated by means of further experiments.     

Prediction of pulmonary edema by plasma protein levels in patients with sepsis

Purpose

The difficulties of fluid therapy in patients with septic shock are to maintain sufficient vascular volume while preventing pulmonary edema formation. Thus, it is important to find a biomarker that can reliably predict pulmonary edema formation after fluid loading. We evaluated the association of plasma protein levels with the increase in extravascular lung water index (ΔEVLWI) after fluid loading.

Methods

This was an observational study in which we retrospectively reviewed medical records of septic patients in whom hemodynamic variables were measured by transpulmonary thermodilution technique before and after fluid loading. Plasma protein levels were measured before fluid loading. Patients were divided into 2 groups according to the changes in EVLWI (ΔEVLWI ≥ 10%) after fluid loading. Diagnostic performance of plasma proteins in predicting pulmonary edema formation was assessed.

Results

A total of 62 patients were included, and 27 of them showed a ΔEVLWI 10% or higher after fluid loading. Plasma albumin and transferrin were significantly lower in this group than in the group with ΔEVLWI less than 10% (21.7 ± 5.8 vs 25.3 ± 5.0 g/L for albumin, P < .05; 107.9 ± 50.1 vs 136.8 ± 44.2 mg/dL for transferrin, P < .05). Areas under the curve of albumin and transferrin were 0.68 (cardiac index, 0.54-0.83) and 0.72 (cardiac index, 0.59-0.86), respectively. At a cutoff value of 87.9 mg/dL, transferrin had a sensitivity of 0.91 in predicting ΔEVLWI 10% or higher.

Conclusions

Plasma transferrin and albumin levels were associated with ΔEVLWI 10% or higher after fluid loading. The high sensitivity of both biomarkers indicated that patients with normal values were less likely to develop pulmonary edema after fluid loading.     

Comparative proteomic analysis of human malignant ascitic fluids for the development of gastric cancer biomarkers

ObjectivesMalignant ascites is a sign of peritoneal seeding, which is one of the most frequent forms of incurable distant metastasis. Because the development of malignant ascites is associated with an extremely poor prognosis, determining whether it resulted from peritoneal seeding has critical clinical implications in diagnosis, choice of treatment, and active surveillance. At present, the molecular characterizations of malignant ascites are especially limited in case of gastric cancer. We aimed to identify malignant ascites-specific proteins that may contribute to the development of alternative methods for diagnosis and therapeutic monitoring and also increase our understanding of the pathophysiology of peritoneal seeding.Design & methodsFirst, comprehensive proteomic strategies were employed to construct an in-depth proteome of ascitic fluids. Label-free quantitative proteomic analysis was subsequently performed to identify candidates that can differentiate between malignant ascitic fluilds of gastric cancer patients from benign ascitic fluids. Finally, two candidate proteins were verified by ELISA in 84 samples with gastric cancer or liver cirrhosis.ResultsComprehensive proteome profiling resulted in the identification of 5347 ascites proteins. Using label-free quantification, we identified 299 proteins that were differentially expressed in ascitic fluids between liver cirrhosis and stage IV gastric cancer patients. In addition, we identified 645 proteins that were significantly expressed in ascitic fluids between liver cirrhosis and gastric cancer patients with peritoneal seeding. Finally, Gastriscin and Periostin that can distinguish malignant ascites from benign ascites were verified by ELISA.ConclusionsThis study identified and verified protein markers that can distinguish malignant ascites with or without peritoneal seeding from benign ascites. Consequently, our results could be a significant resource for gastric cancer research and biomarker discovery in the diagnosis of malignant ascites.     

The occurrence during acute infections of a protein not normally present in the blood. V. Physical-chemical properties of the C-reactive protein crystallized by a modified technique

A method is described for obtaining crystalline C-reactive protein from serous fluids in which the protein is associated with lipid. Most pathological fluids currently available as a source of this protein appear to fall in this category. Crystalline C-reactive protein has its isoelectric point at pH 4.82 as determined by free electrophoresis in McIlvaine's buffer. Its mobility in the electrophoresis cell, both alone and after addition to normal serum, coincides with that of the β-globulin fraction of the serum. In contrast to this finding, by the method of zone electrophoresis on a starch supporting medium the protein migrates with the γ₁-globulin. The significance of this discrepancy is discussed. Studies in the ultracentrifuge indicate an s_20,w of 7.5.     

Treatment of Acute Low Pressure Pulmonary Edema in Dogs: RELATIVE EFFECTS OF HYDROSTATIC AND ONCOTIC PRESSURE, NITROPRUSSIDE, AND POSITIVE END-EXPIRATORY PRESSURE

Severe pulmonary edema sometimes develops despite normal pulmonary capillary wedge pressure (Ppw). The equation describing net transvascular flux of lung liquid predicts decreased edema when hydrostatic pressure is reduced or when colloid osmotic pressure is increased in the pulmonary vessels. We tested these predictions in a model of pulmonary capillary leak produced in 35 dogs by intravenous oleic acid. 1 h later, the dogs were divided into five equal groups and treated for 4 h in different ways: (a) not treated, to serve as the control group (Ppw = 11.1 mm Hg); (b) given albumin to increase colloid osmotic pressure by 5 mm Hg (Ppw = 10.6 mm Hg); (c) ventilated with 10 cm H₂O positive end-expiratory pressure (Peep) (transmural Ppw = 10.4 mm Hg); (d) phlebotomized to reduce Ppw to 6 mm Hg; (e) infused with nitroprusside, which also reduced Ppw to 6 mm Hg. Phlebotomy and nitroprusside reduced the edema in excised lungs by 50% (P< 0.001), but Peep and albumin did not affect the edema. Pulmonary shunt decreased on Peep and increased on nitroprusside, and lung compliance was not different among the treatment groups, demonstrating that these variables are poor indicators of changes in edema. Cardiac output decreased during the treatment period in all but the nitroprusside group, where Ppw decreased and cardiac output did not. We conclude that canine oleic acid pulmonary edema is reduced by small reductions in hydrostatic pressure, but not by increased colloid osmotic pressure, because the vascular permeability to liquid and protein is increased. These results suggest that low pressure pulmonary edema may be reduced by seeking the lowest Ppw consistent with adequate cardiac output enhanced by vasoactive agents like nitroprusside. Further, colloid infusions and Peep are not helpful in reducing edema, so they may be used in the lowest amount that provides adequate circulating volume and arterial O₂ saturation on nontoxic inspired O₂. Until these therapeutic principles receive adequate clinical trial, they provide a rationale for carefully monitored cardiovascular manipulation in treating patients with pulmonary capillary leak.     

Multifunctional amphiphilic ionic liquid pathway to create water-based magnetic fluids and magnetically-driven mesoporous silica

Amphiphilic ionic liquids, 1-alkyl-3-methylimidazolium chloride (C_nmimCl with n = 10, 12, 14, 16) were firstly used as modifiers to construct a self-assembly bilayer on the surface of iron oxide nanoparticles for generation of highly stable, water-based magnetic fluids. Subsequently, a magnet-driven mesoporous silica was synthesized by in situ self-assembly in the bilayer C_nmimCl-stabilized magnetic fluid using the C₁₆mimCl as template and tetraethylorthosilicate (TEOS) as silicon source via a hydrothermal synthesis and following calcination procedure. A systematic study was carried out addressing the influence of the alkyl chain length of C_nmimCl in the primary and secondary layers on the stability of magnetic fluids. The characterization of TEM, XRD, VSM, electrophoresis experiments, TGA and DTA showed that stable water-based magnetic fluids can be synthesized based on the assembly of the well-defined bilayer-C_nmimCl structure with long-chain C₁₆mimCl as secondary layer on the magnetite (Fe₃O₄) nanoparticles. The results of small and wide-angle XRD, TEM, VSM, and N₂ absorption experiments indicated that the nano-scale magnetic Fe₃O₄ particles were inlayed into hexagonal p6mm mesoporous silica (MCM-41 type) framework. Importantly, it was found that the obtained Fe₃O₄/MCM-41 was an appropriate adsorbent for the adsorption of rhodamine B and methylene blue from their aqueous solution. In addition, the adsorbent could be separated and reclaimed fleetly from the solution under external magnetic field.

1-Alkyl-3-methylimidazolium chloride (C_nmimCl) can be used to construct bilayer C_nmimCl stabilized magnetic fluids, and subsequently magnetic mesoporous silica can be prepared by using the C₁₆mimCl as template in the magnetic fluids.     

Knee-extension strength,postural control and function are related to fracture type and thigh edema in patients with hip fracture

Background

Post-surgery thigh edema, loss of knee-extension strength, and reduced physical performance are common following a hip fracture. It is not known if knee-extension strength and physical performance are related to the edema and fracture type. The aim of this study was to examine the influence of fracture type and post-surgery edema on physical performances in patients with hip fracture.

Methods

Fifteen women and five men admitted from their own home to an acute orthopedic hip fracture unit were examined. Ten had cervical and ten had intertrochanteric fractures. Correlations between fracture type and thigh edema in the fractured limb (% non-fractured) to physical performances of basic mobility, postural control (sway), and isometric knee-extension strength were examined. All measures, except those of basic mobility, were conducted at the time of discharge, 8.5 days post-surgery.

Findings

Patients with intertrochanteric fractures had greater edema (111% non-fractured limb) compared with cervical fractures (104% non-fractured, P < 0.001). Thigh edema was significantly correlated to lower scores of basic mobility (r = −0.61, P = 0.004), reduced postural control (r = 0.67, P = 0.001), and fractured limb knee-extension strength deficit ([% non-fractured], r = −0.77, P < 0.001), explaining between 32% and 59% of the variance (r²) in performances.

Interpretation

Our results indicate that fracture type and the corresponding thigh edema are important factors influencing physical performances after hip fracture. These findings have important implications for rehabilitation programs and for further research in patients with hip fracture.     

Total plasma clearance versus urinary plasma clearance of 51Cr-EDTA in patients with cirrhosis with and without fluid retention

Abstract

Background and aim. In patients with fluid retention, the total plasma clearance of ⁵¹Cr-EDTA (Cl_P) may overestimate the glomerular filtration rate (GFR). The present study was therefore undertaken in order to compare Cl_P with the urinary plasma clearance of ⁵¹Cr-EDTA (Cl_U) in patients with cirrhosis with and without fluid retention. Material and methods. A total of 136 patients with cirrhosis (24 without fluid retention, 112 with ascites) received a quantitative intravenous injection of ⁵¹Cr-EDTA followed by plasma and quantitative urinary samples for 5 hours. Cl_P was determined from the injected dose relative to the plasma concentration-time area, extrapolated to infinity. Cl_U was determined as urinary excretion relative to the plasma concentration-time area up to voiding. Results. In patients without fluid retention, the difference between Cl_P and Cl_U (Cl_P ? Cl_U = Cl_Δ) was mean 4.5 mL/min/1.73 m². In patients with ascites, Cl_Δ was significantly higher (17.6 mL/min/1.73 m², p < 0.0001). Cl_Δ increased with lower values of GFR (r = ? 0.458, p < 0.001). Repeated measurements of Cl_U in a subgroup of patients with fluid retention (n = 25) gave almost identical values. Different types of corrections of one-pool clearance were almost identical with Cl_P, except for higher clearance values, which were somewhat underestimated by the former. Conclusion. In patients with fluid retention and ascites Cl_P and corrected one-pool clearance overestimates GFR substantially. Although Cl_U may underestimate GFR slightly, patients with ascites should collect urine quantitatively in order to obtain a reliable measurement of GFR.     

Gamma‐variate plasma clearance versus urinary plasma clearance of 51Cr‐EDTA in patients with cirrhosis with and without fluid retention

In patients with fluid retention, the plasma clearance of ⁵¹Cr‐EDTA (Cl_exp obtained by multiexponential fit) may overestimate the glomerular filtration rate (GFR). The present study was undertaken to compare a gamma‐variate plasma clearance (Cl_gv) with the urinary plasma clearance of ⁵¹Cr‐EDTA (Cl_u) in patients with cirrhosis with and without fluid retention. A total of 81 patients with cirrhosis (22 without fluid retention, 59 with ascites) received a quantitative intravenous injection of ⁵¹Cr‐EDTA followed by plasma and quantitative urinary samples for 5 h. Cl_gv was determined from the injected dose relative to the plasma concentration‐time area, obtained by a gamma‐variate iterative fit. Cl_exp and Cl_u were determined by standard technique. In patients without fluid retention, Cl_gv, Cl_exp and Cl_u were closely similar. The difference between Cl_gv and Cl_u (Cl_gv – Cl_u = ΔCl) was mean ?0·6 ml min^?1 1·73 m^?2. In patients with ascites, ΔCl was significantly higher (11·8 ml min^?1 1·73 m^?2, P<0·0001), but this value was lower than Cl_exp – Cl_u (17·5 mL min^?1 1·73 m^?2, P<0·01). ΔCl increased with lower values of GFR (P<0·001). In conclusion, in patients with fluid retention and ascites Cl_gv and Cl_exp overestimates GFR substantially, but the overestimation is smaller with Cl_gv. Although Cl_u may underestimate GFR slightly, patients with ascites should collect urine quantitatively to obtain a reliable measurement of GFR.     

Alpha-fetoprotein in pericardial,peritoneal, and pleural fluids: A body fluid matrix evaluation

ObjectivesAlpha-fetoprotein (AFP) measurement in pericardial, peritoneal (ascites), and pleural fluids is sometimes requested by clinicians as supportive evidence in the evaluation of suspected malignancy. As commercially available, Food and Drug Administration (FDA)-cleared AFP assays are not validated for these fluid types, laboratories must complete additional validation studies to comply with regulatory requirements for body fluid testing. The objective of this study was therefore to conduct a matrix evaluation for these body fluid types using the Beckman Access AFP assay on the UniCel DxI 800 immunoassay system.Design and methodsUsing an Institutional Review Board (IRB) approved protocol, previously collected pericardial fluid, peritoneal fluid, pleural fluid, and serum specimens were de-identified and frozen at −20 °C prior to matrix evaluation experiments. Spiked recovery, mixed recovery/linearity, and precision studies were conducted.ResultsIn spiked and mixed recovery studies, the average percent (%) recovery was within predefined acceptable limits (±15%) for all three body fluids. Linearity was observed over the analytical measurement range (AMR) for all three body fluids (slope, intercept, systematic error): pericardial 0.988, −0.1, 6.1%; peritoneal 0.986, 0.0, 4.1%; and pleural 1.016, 0.0, 1.6%. Imprecision was ≤6.0% CV for all three body fluids at both high and low AFP concentrations.ConclusionsMatrix interference with AFP testing was not observed for pericardial, peritoneal, or pleural fluids on the Beckman UniCel DxI 800 system.     

INVESTIGATIONS ON THE OCCURRENCE OF Rh SUBSTANCES IN AMNIOTIC FLUID

1. Rh substances are found in amniotic fluid. Not all anti-Rh sera seem to be suitable for the detection of Rh substances in amniotic fluid. Careful selection of Rh antisera, as well as quantitative considerations, determine success or failure of their demonstration. 2. The baby''s Rh type and not the mother''s determines the occurrence of Rh substances in amniotic fluid. 3. There are Rh secretors and Rh non-secretors. At least four out of five individuals are secretors. 4. The secretion of Rh substance into the amniotic fluid would seem to be entirely independent of the secretion of the blood group specific substances. 5. The majority of Rh-positive amniotic fluids seem to contain both Rh₁ and Rh₂ substances. However, in certain instances fluids belonging to the pure Rh₁ type or pure Rh₂ type were found. 6. Three cases of erythroblastosis were described. All three came from Rh-negative mothers with Rh-positive babies. The amniotic fluids of all three failed to reveal the presence of Rh substances.     

Treating Diabetic Ketoacidosis in Children While Preventing Cerebral Edema: One Hospital''s Protocol

One of the main objectives of treatment of DKA in the pediatric patient is the gradual reduction of serum osmolality. This is achieved by conservative fluid resuscitation and avoidance of bolus insulin or the rapid expansion of the extracellular fluid by the use of high volumes of hypotonic fluids.The ED nurse must carefully assess the clinical status of patients with risk factors (young age, duration and severity of symptoms before starting treatment, low Pco₂, high serum urea nitrogen, lack of increase in serum sodium during therapy, and treatment with bicarbonate) and look for subtle changes in neurologic status. If these neurologic changes occur, immediate intervention is necessary. Prompt control of airway and ventilation as well as initiation of hyperosmolar therapy (intravenous mannitol) to reduce swelling in the brain should be initiated.⁷Further studies and new drugs will aid in the treatment of DKA and cerebral edema; however, it will always be important to understand and initiate appropriate treatment for the child and observe for changes in neurologic status. These are the actions that can save a child's life.     

Lung fluid transport in aquaporin-5 knockout mice

The mammalian lung expresses water channel aquaporin-1 (AQP1) in microvascular endothelia, AQP4 in airway epithelia, and AQP5 at the apical plasma membrane in type I cells of alveolar epithelia. We previously studied the role of AQP1 and AQP4 in lung fluid transport using knockout mice. Here, we examined the role of AQP5 using AQP5 knockout mice, which were recently shown to manifest defective saliva secretion. AQP5 deletion did not affect lung morphology at the light microscopic level, nor did it affect the distribution or expression of aquaporins 1, 3, or 4. Airspace-capillary osmotic water permeability (P_f) was measured in isolated perfused lungs by pleural surface fluorescence and gravimetric methods. P_f was reduced 10-fold by AQP5 deletion and was further reduced by 2- to 3-fold in AQP1/AQP5 double-knockout mice. Hydrostatic lung edema in response to acute increases in pulmonary artery pressure was not affected by AQP5 deletion. Active alveolar fluid absorption was measured in an in situ lung model from the increase in concentration of a volume marker in an isosmolar alveolar instillate. Interestingly, fluid absorption did not differ in litter-matched AQP5 knockout mice, nor was there an effect of AQP5 deletion when fluid absorption was maximally stimulated by pretreatment of mice with keratinocyte growth factor. These results indicate that AQP5 is responsible for the majority of water transport across the apical membrane of type I alveolar epithelial cells. The unimpaired alveolar fluid clearance in AQP5-null mice indicates that high alveolar water permeability is not required for active, near-isosmolar fluid transport.     

Plasma-to-ascitic fluid transport rate of albumin in patients with decompensated cirrhosis. Relation to intraperitoneal albumin

Summary. Albumin-kinetics and haemodynamic studies were performed in 20 patients with decompensated liver cirrhosis in order to improve the knowledge on genesis and perpetuation of hepatic ascites, especially with respect to determinants of intraperitoneal protein. A positive relationship was found between the plasma-to-peritoneal transport rate of albumin (index of ‘lymph-imbalance’) and the mass of intraperitoneal albumin (r_log= 0·82, P< 0·001), indicating a significant role of ‘lymph-imbalance’ to sequestration of protein in the peritoneal cavity. Ascitic fluid albumin concentration was on the average 0.22 of that of plasma and directly correlated to the plasma concentration (r_lin= 0·68, P < 0·01). The hydrostatic pressure difference across the splanchnic microvasculature (assessed as wedged hepatic vein minus inferior vena caval pressure) was directly correlated to the effective (plasma minus ascitic fluid) oncotic pressure (r_lin= 0·74, P< 0·001) but significantly higher than that (P<0·005), indicating a ‘non-equilibrium’ in the splanchnic Starling forces. The results point to a multivariate genesis and perpetuation of cirrhotic ascites as laid down in the ‘lymph-imbalance’ theory of ascites formation, whereas a ‘fluid equilibrium’ theory seems to be too simple, especially with respect to explain protein sequestration in the peritoneal cavity.     

Evaluation of Antimicrobial and Lipopolysaccharide-Neutralizing Effects of a Synthetic CAP18 Fragment against Pseudomonas aeruginosa in a Mouse Model

CAP18 (cationic antimicrobial protein; 18 kDa) is a neutrophil-derived protein that can bind to and inhibit various activities of lipopolysaccharide (LPS). The 37 C-terminal amino acids of CAP18 make up the LPS-binding domain. A truncated 32-amino-acid C-terminal fragment of CAP18 had potent activity against Pseudomonas aeruginosa in vitro. We studied the antimicrobial and LPS-neutralizing effects of this synthetic truncated CAP18 peptide (CAP18_106–137) on lung injury in mice infected with cytotoxic P. aeruginosa. To determine its maximal effect, the CAP18_106–137 peptide was mixed with bacteria just prior to tracheal instillation, and lung injury was evaluated by determining the amount of leakage of an alveolar protein tracer (¹²⁵I-albumin) into the circulation and by the quantification of lung edema. The lung injury caused by the instillation of 5 × 10⁵ CFU of P. aeruginosa was significantly reduced by the concomitant instillation of CAP18_106–137. However, the administration of CAP18_106–137 alone, without bacteria, induced lung edema, suggesting that it has some toxicity. Also, the peptide did not significantly reduce the number of bacteria that had been simultaneously instilled, nor did it significantly improve the survival of the infected mice. The addition of CAP18_106–137 to aztreonam along with the bacteria did decrease the level of antibiotic-induced release of inflammatory mediators including tumor necrosis factor alpha, interleukin-6, and nitric oxide and also improved the survival of the mice. Therefore, more investigations are needed to confirm the toxicities and the therapeutic benefits of CAP18_106–137 as an adjunctive therapy to antibiotics in the treatment of infections caused by gram-negative bacteria.     

Edema of Advanced Cancer: Prevalence,Etiology, and Conservative Management—A Single Hospice Cross-Sectional Study

Context

Edema of advanced cancer, seldom recognized in the literature, significantly impairs patient quality of life.