Reversal of protein-energy malnutrition in children during treatment of advanced neoplastic disease.

The effectiveness of enteral and parenteral feeding in supporting a satisfactory nutritional status and/or reversing protein-energy malnutrition was evaluated in 28 children, ages 1-19 (14 female) with advanced malignant disease (21 solid tumors, 7 leukemia-lymphoma). At the onset of treatment, 21 patients received intensive nutritional counseling (INC) and oral supplementation while seven received total parenteral nutrition (TPN). Sixteen of 21 patients who received INC had a decreased intake (x 48 +/- 24%) Recommended Dietary Allowances (RDA) for kilocalories and dramatic weight loss (x 16.4 +/- 12.4%). A total of 18 patients received TPN for a mean of 24 days (7-60); kcal averaged 90 +/- 26% RDA during weight gain. At onset of TPN, the mean serum albumin, transferrin and total lymphocyte counts were 3.06 +/- 0.38 g/dl, 175 +/- 62 mg/dl, and 1102 +/- 966/mm3 respectively, 15/18 children had subnormal anthropometric measurements and 17/18 patients were anergic to recall skin test antigens. TPN for less than 9-14 days neither repleted weight, skinfold reserves, nor serum albumin concentrations (greater than 3.2 g/dl) although an early increase (p less than .02) in transferrin concentration was observed. However, TPN for 28 days supported weight gain (3.27 kg, 16 +/- 6%), increased serum albumin (0.62 +/- 0.43 g/dl, p less than .001) and transferrin (62 +/- 42, p less than .002) to normal concentrations and reversed anergy in 7/11 patients retested. This study documents the severity of protein energy malnutrition which accompanies intense treatment of children with cancer and the nutritional and immunological benefits of a 28 day course of TPN.     

The effect of prenatal protein-energy malnutrition on collagen metabolism in fetal bones

We analyzed various biochemical variables of the bones in fetal rats whose dams were protein-energy malnourished. Dams were randomly divided into two groups and fed either a 6% protein diet as a malnourished group or a 20% protein diet as a control, from day 13 of gestation to day 22, when fetuses were removed. Hexosamine and hydroxyproline contents of the calvaria and hexosamine contents of long bones were greater in the malnourished group than in the controls. Sequential extractability of collagen differed among various bones in the malnourished group and controls. The ratio of alpha:beta obtained from SDS-polyacrylamide gel of neutral salt-soluble collagen tended to increase in the long bones and mandible, and decrease in the calvaria and ribs in the malnourished group. Also, the ratio of alpha 1:alpha 2 tended to be lower in the malnourished group than in the control group in all bones. Protein-energy malnutrition during pregnancy has shown to affect biochemical composition of various fetal bones.     

Liver function tests in surgical infection and malnutrition.

Liver function tests were studied in chronically infected surgical patients, patients who recovered from infection, nonseptic malnourished patients and healthy control subjects. Liver function tests were abnormal in the septic patients but returned to normal values upon recovery from infection despite persistent loss of body weight. Malnourished, nonseptic patients similarly had normal liver function tests. These findings suggest that infection rather than accompanying malnutrition is the major cause of the abnormal liver function tests commonly observed in chronically septic surgical patients. Standard liver function tests may be helpful both in the diagnosis of occult intra-abdominal sepsis and also in indicating the efficacy of its treatment.     

Impaired fracture healing in macrophage migration inhibitory factor-deficient mice

Summary  

This study investigated the role of macrophage migration inhibitory factor (MIF) in fracture repair using MIF gene-deficient mice (MIF KO). Fracture healing was delayed in MIF KO, and this was mainly due to the delay in the mineralization of osteoid within the fracture callus.     

The effects of prenatal protein-energy malnutrition on ossification of fetal rat bones: a biochemical study

In fetal rats whose dams were fed a low-protein diet, 35S sulfate uptake into the growth plate of the long bone and rib was higher than in the control group. The elution pattern of guanidine-HCl extract in gel chromatography revealed that the malnourished group had more high molecular weight proteoglycans in the dissociative condition and a larger aggregated portion in the associative condition than did the control group; however, the same chondroitin-sulfate chain size existed. Calcium content did not differ in both groups. Aggregated proteoglycan or a high molecular weight proteoglycan that existed in the malnourished group probably played an inhibitory role in calcification. Prenatal protein-energy malnutrition may delay the change of proteoglycan character, which could affect mineralization of fetal bones.     

Effects of laparotomy on systemic macrophage function.

Surgical trauma induces immunosuppression that may adversely influence survival. This study examined the effect of laparotomy on two different macrophage populations, peritoneal macrophages (PM phi) and Kupffer cells. Female, 6- to 8-week old, CFW/C3H-HeN mice (n = 160) were randomly allocated to one of three study groups: control, ether anesthetic only, or ether anesthetic and laparotomy. On postoperative days 1 and 3, PM phis and Kupffer cells were harvested and assayed for superoxide anion production (O2-), percent macrophage phagocytosis of Candida albicans (CAP), percent C. albicans killed by macrophages (CAK), percent major histocompatibility complex (MHC)-class II antigen expression, and antigen presentation. Macrophages isolated on postoperative day 1 were also cocultured with 100 units/10(6) cells/ml interferon-gamma (IFN-gamma). Laparotomy significantly impaired microbicidal activity (O2-, percent CAP, and percent CAK) and antigen presentation on postoperative day 1. On postoperative day 3, O2- and antigen presentation were increased significantly (p less than 0.05) over control values, indicating a rebound phenomenon. Kupffer cell microbicidal function was unchanged on postoperative days 1 and 3. The initial immune impairment (PM phis: O2-, CAP, and CAK) was abrogated by IFN-gamma treatment. In immunosuppressed hosts after injury, administration of macrophage-activating factors such as IFN-gamma could be of therapeutic benefit.     

Impaired immune function in obstructive jaundice

Sepsis is a common and occasionally lethal complication of obstructive jaundice. The reasons for this increased susceptibility to infection are unknown. This study examines lymphocyte and reticuloendothelial (RES) function in animals with obstructive jaundice. Twelve New Zealand white rabbits (3-4 kg) were studied. Lymphocyte function was evaluated in six rabbits by phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) stimulation. In six animals, hepatic RES function was assessed by calculating the phagocytic index (PI) using the disappearance of 99Tc sulfacolloid (5 mg/kg) iv. After baseline studies, the common bile duct was divided and ligated. The above studies and serum bilirubin were repeated at 3 weeks. Obstruction was then relieved by cholecystojejunostomy (CJ) and RES studies repeated monthly x 6. Preobstructive lymphocyte function showed a stimulation index ratio (log) of 0.85 +/- 0.25 for PHA, 0.75 +/- 0.3 for Con A, and 0.71 +/- 0.25 for PWM. With biliary obstruction, the values fell to -0.23 +/- 15 (P less than 0.006), -0.31 +/- 0.12 (P less than 0.006), and -0.29 (P less than 0.006), demonstrating impaired lymphocyte function. When tested lymphocytes were mixed with control pooled rabbit serum, however, no lymphocyte impairment was noted. Baseline hepatic PI was 6.02 +/- 0.18 and fell to 3.79 +/- 0.33 with obstruction (P less than .01) and remained low at (3.20 +/- 0.14) 1 month (P less than 0.01) and (3.33 +/- 0.23) at 3 months (P less than .01), after CJ but returned to normal (8.04 +/- 0.97) at 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Investigation of alveolar macrophage function using lucigenin-dependent chemiluminescence.

The method using lucigenin-dependent phagocytic chemiluminescence is described for the assessment of alveolar macrophage metabolic activity in response to stimulation by opsonised particles or soluble agents. The requirement for superoxide anion (O2-) in the production of chemiluminescence is suggested by inhibition (95%) using superoxide dismutase. The results obtained are correlated with those obtained using another method of detecting O2- release (r = 0.61; p less than 0.05) and are also related by regression analysis to polymorphonuclear leucocyte contamination of the alveolar macrophage suspension. This shows that alveolar macrophages produce lucigenin-dependent chemiluminescence of the same order of magnitude as do polymorphonuclear leucocytes.     

Beneficial effect of enhanced macrophage function in the trauma patient.

Host immunosuppression after trauma contributes to septic morbidity. The macrophage is a key element in the host immune response. This study evaluated glucan, a macrophage stimulant, in a prospective, randomized, double-blind study of 38 trauma patients undergoing surgery. Glucan (21 patients), 50 mg/m2, or placebo (17 patients) was given intravenously daily for 7 days. Delayed hypersensitivity skin testing was performed on days 1 and 7 after trauma. Serum interleukin-1 (IL-1) and tumor necrosis factor (TNF) were assayed after trauma. While the total mortality rate was significantly less in the glucan group (0% versus 29%) (p less than 0.05), the mortality rate from sepsis was not statistically different (0% versus 17.6%). Glucan therapy significantly decreased septic morbidity (9.5% versus 49%; p less than 0.05). Serum IL-1 had a greater increase in glucan patients on day 3 after trauma (143.4 +/- 19.3% versus 78.6 +/- 11.7%; p less than 0.05), but there was no difference thereafter. Serum TNF did not vary between groups. Early increase in IL-1 correlated with subsequent skin test conversion to positive. Neither serum IL-1 nor TNF was a reliable indicator of future sepsis. Further clinical trials are indicated to evaluate biologic response modifiers that activate macrophages in the trauma patient.     

Impaired function of endothelial pressure-activated cation channel in salt-sensitive genetic hypertension.

Mechanosensitive ion channels have been suggested to act as endothelial mechanosensors for hemodynamic forces. The present study tested the hypothesis that the pressure-activated cation channel (PAC), a novel type of endothelial mechanosensitive ion channel, is involved in salt sensitivity in the Sabra rat model of hypertension. Groups of Sabra salt-sensitive (SBH/y) and salt-resistant (SBN/y) rats were loaded with deoxycorticosterone-acetate (DOCA)-salt for 8 wk or were fed a regular diet. Single channel function of PAC in SBH/y and SBN/y rats was investigated in intact endothelium of mesenteric artery using the patch-clamp technique. After DOCA-salt treatment, the SBH/y rats showed a full hypertensive response, whereas SBN/y rats were normotensive. Rats of both strains that received a regular diet were normotensive. In endothelium of both Sabra rats, Ca(2+) permeable PAC that was activated by positive pipette pressures was identified. Apparent PAC density (percentage of patches with PAC activity) was reduced in hypertensive SBH/y rats that were loaded with DOCA-salt compared with salt-loaded normotensive SBN/y rats (6 +/- 2% versus 24 +/- 8%, respectively; P < 0.05). In normotensive SBH/y and SBN/y rats that received a regular diet, PAC density was not altered. Mechanosensitivity and unitary conductance of endothelial PAC were similar in both strains under a regular diet as well as salt loading with DOCA-salt. In conclusion, the decreased density of PAC in mesenteric endothelium from hypertensive SBH/y rats indicates an impaired ion channel regulation. The defective PAC function presumably leads to an impaired mechanosensitive Ca(2+) entry and might contribute to endothelial dysfunction and high BP in this type of salt-sensitive genetic hypertension.     

严重烫伤后腹腔巨噬细胞游离钙及抗原提呈功能的实验研究

我们对严重烫伤小鼠腹腔巨噬细胞内游离钙PM(?)[Ca~(2 )]和抗原提呈(AP)功能进行了动态观察,结果显示:体外未受刺激的PM(?)[Ca~(2 )]在烫伤后12、24、72h均显著升高。这证明烫伤后早期PM(?)在体内就已被激活。加A23187刺激的PM(?)[Ca~(2 )]在伤后虽无显著升高,但也提示PM(?)处于高度活化,甚至过度活化的状态。严重烫伤后可使PM(?)的AP能力明显低下,其不仅发生早,而且持续时间较久,可能已成为伤后特异性免疫功能受抑制的主导因素。M(?)体内活性的改变则可能是烧伤后M(?)免疫功能异常的基础。     

严重烫伤后腹腔巨噬细胞游离钙及抗原提呈功能的实验研究

我们对严重烫伤小鼠腹腔巨噬细胞内游离钙ＰＭ［Ｃａ２＋］ｉ和抗原提呈（ＡＰ）功能进行了动态观察，结果显示：体外未受刺激的ＰＭ［Ｃａ２＋］ｉ在烫伤后１２、２４、７２ｈ均显著升高。这证明烫伤后早期ＰＭ在体内就已被激活。加Ａ２３１８７刺激的ＰＭ［Ｃａ２＋］ｉ在伤后虽无显著升高，但也提示ＰＭ处于高度活化，甚至过度活化的状态。严重烫伤后可使ＰＭ的ＡＰ能力明显低下，其不仅发生早，而且持续时间较久，可能已成为伤后特异性免疫功能受抑制的主导因素。Ｍ体内活性的改变则可能是烧伤后Ｍ免疫功能异常的基础。     

Elemental diet alters macrophage function in mice

Administration of a chemically defined liquid elemental diet (ED) induces spontaneous bacterial translocation to mesenteric lymph nodes (MLN) in animal models. The influence of this process on host immunity is unclear. This study evaluated the effects of ED on peritoneal macrophage (PM phi) antimicrobial functions. Conventional C57/BL6 mice and endotoxin-resistant C3H/HeJ mice (n = 60) were randomized to be pair-fed either an ED or regular chow diet (RD) for 14 days. Blood, spleen, liver, and MLN were cultured for bacteria. PM phi were harvested for: percentage Candida albicans (CA) phagocytosis, percentage killing of CA, PM phi superoxide anion (O2-) production, and TNF-dependent macrophage cytotoxicity. Enteral feeding of ED in conventional C57/BL6 mice caused significant bacterial translocation to MLN but not other organs. Significant impairment of CA killing by PM phi occurred in the ED group and was associated with reduced O2- production. Tumor necrosis factor (TNF)-dependent cytotoxicity of PM phi was also decreased. In endotoxin-resistant C3H/HeJ mice, bacterial translocation was not observed and PM phi antifungal functions remained similar in both RD and ED groups. Thus, enteral feeding of an elemental diet downregulates host oxidative and antimicrobial mechanisms and TNF-dependent cytotoxicity in conventional mice which may be secondary to elemental diet-induced bacterial translocation.     

Impairment of pulmonary macrophage function with total parenteral nutrition.

OBJECTIVE: The effects of total parenteral nutrition (TPN) administration on pulmonary macrophage function and host response to gram-negative pulmonary infection were evaluated. SUMMARY BACKGROUND DATA: Administration of TPN resulted in increased infectious complications in traumatized and perioperative patients, but underlying mechanisms are unclear. METHODS: Twenty-six male Wistar rats underwent central vein cannulation and were randomized to isocaloric feeding of a regular chow diet (RD) plus saline infusion or TPN without chow diet for 7 days. Pulmonary alveolar macrophage (PAM phi) superoxide production, Candida albicans phagocytosis and killing, and tumor necrosis factor (TNF) production in response to endotoxin (LPS) were assessed. Mesenteric lymph nodes (MLN) were cultured. A second group of rats (n = 6/group) were inoculated intratracheally with a sublethal dose of 9 x 10(9) live Escherichia coli per animal, and the lungs were cultured quantitatively 72 hours later to assess bacterial clearance. Finally, 11 RD-fed rats and 13 TPN-fed rats received intratracheal inoculation of 1.4 x 10(10) live E. coli and were included in follow-up. RESULTS: Administration of TPN was associated with a significant increase in bacteria positive MLN compared with those in the RD group (p < 0.01). Pulmonary alveolar macrophage superoxide production, Candida albicans phagocytosis and killing, TNF production, and pulmonary clearance of bacteria were decreased significantly in TPN-fed rats compared with those fed a regular chow diet (p < 0.05). These pulmonary macrophage function changes were associated with a significantly higher mortality in TPN-fed rats compared with RD-fed rats after higher dose pulmonary E. coli inoculation. CONCLUSIONS: Defective host pulmonary antimicrobial immune responses during TPN are associated with intestinal bacterial translocation, and may explain increased infectious complications.     

Impaired long-term quality of life in survivors of severe sepsis

Objectives

The present study was undertaken to evaluate the long-term health-related quality of life (HRQOL) as well as the employment status in survivors of severe sepsis up to 6 years afterwards.

Material and methods

From January 2003 to December 2008 a total of 112 severe sepsis and 112 age, gender and Charlson comorbidity index-matched non-septic critically ill patients from 4 university hospital intensive care units (ICU) were enrolled in the study and 126 age and gender-matched community residents were interviewed as the community control group.

Results

A total of 66 (58.9?%) severe sepsis and 80 (71.4?%) non-sepsis critically ill patients survived during the long-term follow-up time. Between August and December 2010 a total of 75 patients including 42 survivors of severe sepsis and 33 critically ill controls completed the face-to-face interview. There were no differences in the long-term HRQOL in terms of Short-Form 36 criteria between severe sepsis and non-sepsis critically ill survivors. However, when compared with the community controls, HRQOL in survivors of severe sepsis showed a significantly and clinically meaningful decrease, with a lower physical functioning (p?=?0.016), vitality (p?=?0.037), role-emotional (p?=?0.043), mental health (p?=?0.038) and mental component scores (p?=?0.042). In addition, the criteria returning to work at 1 year and at the time of interview in severe sepsis survivors were similar with those in critically ill survivors (60.5?% vs. 70.0?%, p?=?0.41 and, 71.1?% vs. 76.7?%, p?=?0.602).

Conclusions

The HRQOL in survivors of severe sepsis was impaired even up to 6 years after hospital discharge.