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In a previous study, we demonstrated the presence of a neutrophil recruitment inhibitory factor (NRIF) in the supernatants of LPS-stimulated macrophages. Recently, the purification of a 54 kDa protein, identified as the macrophage-derived neutrophil chemotactic factor (MNCF) was reported. Since NRIF and MNCF are obtained under the same conditions, and, since the intravenous administration of TNF-α and IL-8 inhibits neutrophil migration, we have investigated whether MNCF could be responsible for this inhibitory activity. After affinity chromatography of the macrophage supernatants on a D-galactose column, the inhibitory activity was recovered in both the unbound (D-gal−) and bound (D-gal+) fractions, with MNCF being found in the D-gal+ fraction. Further gel filtration of the latter on Superdex 75 yielded a single peak containing both activities. In a cytotoxicity assay, most of the TNF found in the crude supernatants was recovered in the D-gal− fraction. Furthermore, the incubation of the D-gal− fraction with anti-TNF-α plus anti-IL-8 antisera partially prevents its inhibitory effect on neutrophil migration, but had no effect on the D-gal+ activity. Overall, these results suggest that the D-gal− inhibitory effect is partially mediated by TNF-α and IL-8, and that MNCF accounts for the inhibition of neutrophil migration in vivo by the D-gal+ fraction.

We have recently described the purification of a 54 kDa acidic protein, identified as macrophage-derived neutrophil chemotactic factor (MNCF). This protein causes in vitro chemotaxis as well as in vivo neutrophil migration even in animals treated with dexamethasone. This in vivo chemotactic activity of MNCF in animals pretreated with dexamethasone is an uncommon characteristic which discriminates MNCF from known chemotactic cytokines. MNCF is released in the supernatant by macrophage monolayers stimulated with lipopolysaccharide (LPS). In the present study, we describe some biological characteristics of homogenous purified MNCF. When assayed in vitro, MNCF gave a bell-shaped dose–response curve. This in vitro activity was shown to be caused by haptotaxis. Unlike N-formyl-methionylleucyl- phenylalanine (FMLP) or interleukin 8 (IL-8), the chemotactic activity of MNCF in vivo and in vitro, was inhibited by preincubation with D-galactose but not with D-mannose. In contrast with IL-8, MNCF did not bind to heparin and antiserum against IL-8 was ineffective in inhibiting its chemotactic activity. These data indicate that MNCF induces neutrophil migration through a carbohydrate recognition property, but by a mechanism different from that of the known chemokines. It is suggested that MNCF may be an important mediator in the recruitment of neutrophils via the formation of a substrate bound chemotactic gradient (haptotaxis) in the inflamed tissues.

Background: More surgical interventions are being performed on octogenarian patients. The aim of this study was to identify factors associated with operative mortality and to determine if perioperative transfusions could affect mortality outcomes in a nonselected series of octogenarian patients undergoing surgery., Methods: A descriptive cross-sectional study was performed on a population of 413 consecutive patients over 80 years old, treated surgically, and divided into two groups: transfused and nontransfused patients. The following variables were recorded: sociodemographic characteristics, main diagnoses, surgical procedure and its characteristics, ASA score, Charlson comorbidity index (CCI), National Nosocomial Infection Surveillance (NNIS) index, transfusion requirements, the Clavien-Dindo classification of surgical complications, and operative mortality., Results: The mean age of the patients was 84.5 years (SD + 3.6). Transfused (25.2 %) and nontransfused patients had similar characteristics; except for neoplasia (P <0.001), NNIS (P = 0.008), operative mortality (P = 0.004), and complications according to Clavien-Dindo score (P <0.001). Operative mortality was 20.1 % (83 patients). The predictive variables associated with operative mortality were ASA score (P <0.001), emergency surgery (P <0.001), and blood transfusion (P = 0.004). After adjusting for the variables age, ASA class, NNIS, emergency surgery, and neoplasia, the multivariate analysis showed that the perioperative transfusion in octogenarian patients continued to be significantly associated with operative mortality (P = 0.019; OR 1.97, 95 % CI 1.12-3.47)., Conclusion: Perioperative transfusion is an independent predictor of postoperative mortality in surgical octogenarian patients.

Introduction: Acute intestinal ischemia is in most cases a lethal condition with a low survival rate. Risk factors of perioperative mortality are poorly defined. The aim of this study was to define risk factors that predict an adverse outcome of acute mesenteric ischemia (AMI)., Methods: A total of 132 consecutive patients (73 men, 59 women), mean+/-SD age 71.96+/-13.64 years, who underwent surgery because of AMI in a university tertiary care center were evaluated over a period of 10 years. Clinical features, laboratory findings, etiologic factors, and surgical procedures were recorded and assessed as possible risk factors for perioperative mortality., Results: Of 132 patients, 86 (65.2%) died during the perioperative period as a direct result of AMI. Significant univariate predictors of perioperative mortality were age (P=0.01), cardiopathy (P=0.002), digoxin intake (P=0.015), shock (P=0.01), urea plasma level (P<0.001), creatinine (P<0.001), potassium (P=0.042), low pH (P=0.015) and bicarbonate (P=0.035); hemoglobin>or=2.48 mmol/L (P=0.035); time delay to surgery (P=0.023); colonic involvement (P<0.001); small and large bowel involvement (P<0.001); arterial versus venous ischemia (P=0.007); and intestinal resection (P<0.001). In the multivariate analysis, the variables previous cardiac illness (P=0.045), urea plasma levels (P<0.001), and small and large bowel involvement were identified as independent risk factors of perioperative mortality. Intestinal resection (P<0.001) was a favorable predictor., Conclusions: Age, time delay to surgery, shock, and acidosis significantly increase the risk of mortality due to AMI, whereas intestinal resection has a protective effect. However, only previous cardiac illness, acute renal failure, and large bowel ischemia have a negative effect as independent risk factors of mortality of AMI.

Background: High grade astrocytomas account for approximately 40% of all primary brain tumors. The median survival is approximately 8-10 months for patients with glioblastoma multiforme and 36 months for patients with anaplastic astrocytoma. The results of systemic chemotherapy in the treatment of brain tumors have been reported to be less than satisfactory, mainly because of the blood-brain barrier impermeability for chemotherapeutic drugs. Intraarterial chemotherapy has been an attractive alternative with which to overcome this problem., Methods: Eighty-three patients with high grade astrocytoma (glioblastoma multiforme [63 patients] and anaplastic astrocytoma--[20 patients]) were treated with intraarterial (intracarotid and/or intravertebral) chemotherapy and radiation therapy between 1987 and 1997. Patients received cisplatin, 60 mg/m2, and etoposide, 40 mg/m2. Radiation therapy was delivered either after completion of the chemotherapy or concomitantly with the chemotherapy., Results: Thirty-four of 71 evaluable patients with high grade astrocytoma (48%) responded to the chemotherapy. The median survival for patients with glioblastoma multiforme who received chemotherapy prior to radiation therapy was 20 months versus 7 months for those patients who underwent concomitant chemotherapy/radiation therapy. Patients with anaplastic astrocytoma who received chemotherapy prior to radiation therapy had a median survival of 45 months compared with 12 months for patients who received concomitant chemotherapy/ radiation therapy. The toxicity profile has been reported to be mild and well tolerated., Conclusions: Intraarterial chemotherapy for patients with glioblastoma multiforme, delivered prior to radiation therapy, appears to result in a median survival three times longer than that achieved with concomitant chemotherapy/radiation therapy. In addition, patients appear to survive substantially longer than they do after radiation therapy with the addition of systemic chemotherapy. Side effects are reported to be acceptable.

The partitioning of pristinamycins was studied in dextran and polyethylene glycol (PEG) aqueous two-phases systems. Pristinamycins partitioned preferentially into the PEG-rich top phase. The partition coefficient was independent of molar mass of PEG and dextran and of antibiotic concentration, but, increased exponentially with the tieline length of the system. Partition of pristinamycins was greatly improved when fatty acids esters of PEG were mixed with PEG. In such mixtures, the partition of coefficient increased up to a value of 24, dependent on the carbon chain length of fatty acids and the modified PEG concentrations. Moreover, in such system, the two groups of pristinamycins, I and II, were extracted in accordance with their hydrophobicity. Recovery of pristinanamycins produced by Streptomyces pritinaespiralis in a fermentation broth was achieved with a dextran/PEG system. Cells were confined into the bottom phase and pristinamycins partitioned in the top phase. However, due to binding of the pristinamycins to the cells, the partition coefficient was slightly lower than of pure antibiotics solutions. (c) 1994 John Wiley & Sons, Inc.

Chemotherapy for tumors of the central nervous system has a limited efficacy presumably because of restricted blood-brain barrier permeability. The advantage of regional intra-arterial administration of anticancer drugs is an increased uptake during the first passage of the drugs through tumor capillaries. Twenty patients with high-grade astrocytomas (HGA) and 28 patients with metastatic brain tumors (MBT) received intracarotid/intravertebral infusion of etoposide and cisplatin. Eight patients with HGA who underwent incomplete resection responded to chemotherapy alone. Four additional patients had complete resection of the tumor. Median survival time of the group (responders and nonresponders) has been 14 months. Twelve patients with MBT responded to chemotherapy alone (six had complete response [CR], and six had partial response [PR]) with a median survival time of 7 months. Intra-arterial chemotherapy (IAC) appears to be effective with acceptable toxicities. Accrual of additional patients is required before a final conclusion can be reached.