Systemic effects of different perfluorochemical agents

Purpose: An intravitreal injection of Fluosol-DA leads to a higher alteration of the macrophage system of the retina than perfluorooctane and perfluorodecalin administered by the same route. The difference may be due to different kinds of oxidative damage caused by the three chemicals. To test the validity of this assumption, the degree of cell alteration, expressed as reduction of cytoplasmic motility, caused by these three perfluorochemicals was examined. Methods: Using the hepatic macrophage system of the rat, cell alteration was examined by magnetometry after intravenous application of various perfluorochemicals [emulsified perfluorodecalin (C₁₀F₁₈), perfluorooctane (C₈F₁₇Br) and Fluosol-DA (corresponding to a 20% emulsion of 70% perfluorodecalin and 30% perfluorotripropylamine, C₉F₂₁N)]. Results: After administration of high doses, all perfluorochemicals led to cytoskeleton alteration. This alteration, expressed as retardation of the relaxation period of ferromagnetic iron oxide particles, was most pronounced after administration of Fluosol-DA. Conclusion: The compromising effect of perfluoro-chemicals is dose dependent and differs among the three compounds tested, with Fluosol-DA showing the greatest decrease in cytoplasmic motility.     

Local effects of different perfluorochemical agents

Purpose: To clarify whether the prolonged presence of perfluorochemicals (PFC) in the vitreous cavity causes oxidative tissue damage and inflammatory response of the retina and, if so, what the process is. Methods: After three different perfluorochemicals [perfluorodecalin (C₁₀F₁₈), perfluorooctane (C₈F₁₈) and Fluosol-DA (corresponding to a 20% emulsion of 70% PFD and 30% perfluorotripropylamine, C₉F₂₁N)] had been in the vitreous cavity of rabbits for 2 weeks, lipid peroxide concentration and myeloperoxidase activity in the retina were determined. Results: Whereas only Fluosol-DA showed significant oxidative damage, the inflammatory activity was significantly increased in all groups. Conclusion: The increased myeloperoxidase activity and the observed oxidative damage of the retina seem to be the effect of both perfluorochemical-loaded macrophages and inflammatory-induced lipid peroxidation.     

Opportunities for pharmaceutical care with critical pathways

Critical pathways are multidisciplinary tools designed to improve patient care and efficiency. Almost every path requires some type of pharmacotherapeutic intervention, from selection of surgical prophylaxis to management of anticoagulation. Pharmacists should become involved with the critical pathway process because it offers an excellent opportunity to incorporate pharmaceutical care and to meet Joint Commission on Accreditation of Healthcare Organization compliance criteria.     

Analysis of premature termination in inpatient psychosomatic rehabilitation based on epidemiologic data from two hospital companies

Premature termination of inpatient psychotherapy can have multiple, mostly negative, effects for patients, therapists, clinics, insurance companies, and employers, but research regarding inpatient settings is still deficient. The analysis of two sets of data of four different rehabilitation clinics from two different hospital companies (2699 and 2215 patients, respectively), aimed at possible predictors and outcomes of premature termination. We found ratios of premature termination of 8.3% and 14.7%, respectively. Especially young patients under 30 years of age and patients with eating and personality disorders were more likely to terminate inpatient treatment prematurely. Treatment outcome as rated by therapists was in significantly fewer cases among premature terminators than among successful terminators improved. The results seem to indicate, that assignment to inpatient psychotherapy can be optimized. For a better understanding of the process of premature termination more theory guided prospective and followup studies are necessary.     

Expression of major histocompatibility class II antigens on polymorphonuclear neutrophils in patients with Wegener's granulomatosis

BACKGROUND: Wegener's granulomatosis is a systemic inflammatory disease of unknown etiology. Many studies suggest that autoimmune reactions are involved, and there is good evidence for the participation of immunocompetent cells. In that context, we examined the activation of polymorphonuclear neutrophils (PMNs) of patients with Wegener's granulomatosis. METHODS: In a prospective study, the expression on the surface of PMNs of CD64 and of the major histocompatibility class II (MHC II) antigen was measured by cytofluorometry in whole blood. The expression of those antigens was correlated to disease activity. RESULTS: Up to 15% of the peripheral PMNs of patients with active disease expressed MHC II. Follow-up studies showed that expression correlated closely with disease activity and that it decreased rapidly under immunosuppressive therapy. Expression of CD64 was seen in approximately 50% of the patients, regardless of disease activity. CONCLUSION: MHC II expression on PMNs might serve as a novel diagnostic marker for active disease and appears to be suitable for monitoring immunotherapy. Moreover, our data provide evidence that PMNs, which are normally MHC II negative, acquire MHC II antigens in the course of disease and may be an unrecognized function within the afferent limb of the immune response.     

Tumor necrosis factor-alpha during continuous high-flux hemodialysis in sepsis with acute renal failure

Suppressed ex vivo endotoxin (ET)-induced production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), in isolated mononuclear cells (PBMCs) is associated with fatal outcome in severe sepsis. PBMCs from surviving patients, but not those from nonsurviving patients, recover their capacity to produce normal amounts of TNF-alpha. We tested the influence of two modalities of continuous renal replacement therapy (CRRT) on ex vivo-induced whole-blood production of TNF-alpha and inhibitory TNF-soluble receptor type I (TNFsRI) in 12 patients with acute renal failure and sepsis (APACHE II score 22 to 30). METHODS: Standard continuous venovenous hemofiltration (CVVH; 36 liters of bicarbonate substitution fluid per day) was performed in 7 patients using polyamid hemofilters (FH66; Gambro). In an additional five patients, we performed daily 18 hours of high-flux hemodialysis (CHFD) using polysulfon F60S dialyzers (Fresenius) and 75 liters of bicarbonate dialysate using the GENIUS single-pass batch dialysis system. Samples were separated from the blood circuit as well as from the ultrafiltrate/spent dialysate lines at the start, during, and end of treatment. Whole-blood samples were incubated with 1 ng/ml of ET for three hours at 37 degrees C. Ultrafiltrate or dialysate samples were incubated with donor whole blood in the presence of ET to measure suppressing activity in ultrafiltrate and spent dialysate. RESULTS: At the start of CRRT, ET-induced whole-blood TNF-alpha production was suppressed to approximately 10% of that in normal controls. During CVVH, median ET-induced TNF-alpha production increased from 0.35 ng/ml at the start to 1.2 ng/ml at three hours, but decreased to pre-CVVH levels at the end of a 24-hour period. In contrast, in patients on CHFD, the median ET-induced TNF-alpha production was 0.5 ng/ml at the start, 1.1 ng/ml at 3 hours, 1.6 ng/ml at six hours, and 1.5 ng/ml at the end of 18 hours of treatment. The ultrafiltrate obtained after three hours of CVVH did not contain suppressing activity. In CHFD, the spent dialysate as compared with fresh dialysate suppressed ET-induced TNF-alpha production in donor blood by 33% throughout the 18 hours of treatment. Whole-blood production of TNFsRI did not change significantly at any time point during CVVH or CHFD. CONCLUSION: These data suggest that high-volume CHFD is superior to standard CVVH in removing a suppressing factor of proinflammatory cytokine production. As CVVH only transiently improves TNF-alpha production, it is most likely that the putative suppressing factor is removed because of saturable membrane adsorption in CVVH. In CHFD, there is a combination of adsorption and detectable diffusion into the dialysate. It remains to be shown whether a further increase in the volume of dialysate per day is able to not only improve but normalize the cytokine response and improve outcome in septic patients with acute renal failure.