Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: relationship to treatment method and atherosclerotic disease

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Its concentration is elevated in patients with end-stage renal disease (ESRD), in part because it is excreted via the kidneys. In this study, the plasma concentrations of ADMA, symmetric dimethylarginine, and L-arginine were determined in relation to plasma nitrate levels (as an index of NO formation) for a group of 80 patients with ESRD. The effects of two treatment methods, i.e., hemodialysis (HD) and peritoneal dialysis (PD), and the role of the presence of atherosclerotic disease were evaluated. Forty-three patients receiving HD and 37 patients receiving PD were compared with healthy control subjects. Plasma L-arginine and dimethylarginine levels were determined by HPLC, using precolumn derivatization with o-phthaldialdehyde. Plasma nitrate levels were determined by gas chromatography-mass spectrometry. Predialysis ADMA concentrations in HD-treated patients were approximately sixfold higher than those in the control group (6.0+/-0.5 versus 1.0+/-0.1 micromol/L; P < 0.05). Plasma nitrate concentrations were significantly lower in HD-treated patients, which suggests that ADMA may inhibit NO synthase. In contrast, plasma ADMA levels and nitrate concentrations in PD-treated patients were similar to those in control subjects. Plasma L-arginine concentrations were not significantly decreased in patients with ESRD. ADMA concentrations were significantly decreased 5 h after HD, compared with baseline values. ADMA levels were significantly higher in HD-treated patients with manifest atherosclerotic disease than in HD-treated patients without atherosclerotic disease (7.31+/-0.70 versus 3.95+/-0.52 micromol/L; P < 0.05). This study confirms that ADMA is accumulated in ESRD. PD-treated patients exhibit significantly lower ADMA levels than do HD-treated patients. Accumulation of ADMA may be a risk factor for the development of endothelial dysfunction and cardiovascular disease in patients with ESRD.     

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.     

Medicolegal aspects of imaging and Internet communications

Many facial plastic surgeons have set up their own personal World Wide Web (WWW) pages with an electronic mail link to communicate with and educate prospective patients. The possible dilemma is in that these services are provided without actually meeting patients face to face. Also, despite the growing popularity of computer imaging systems, it is not clear whether the medical and legal advantages of using such a system outweigh the disadvantages. The purpose of this article is to evaluate these aspects and to provide some protective guidelines. An examination of possible causes of actions arising from computer imaging suggests that surgeons who follow a few simple guidelines, and who use computer imaging responsibly and cautiously, minimize their legal liability. Issues surrounding Internet discussion groups, posted medical advice, intellectual property, and the use of an electronic mail link are also discussed.     

Pediatric cataracts.

There have been major changes over the past 5 to 10 years in our understanding of both the chemical basis for and the surgical treatment of cataract in infants and children. Important questions that remain to be answered include the appropriate power and design selection criteria for intraocular lens implantation, as well as management of the posterior capsule and long-term refractive sequelae. In the past 10 years, there have been radical changes in the management of visually significant cataract in the infant and child. Whereas lens removal, subtotal posterior capsulectomy, vitrectomy, and aphakia were once the standard of care, many physicians now feel that small incisions, phacoemulsification technology, and intraocular lenses (IOLs) are best for these patients. Work is continuing to accumulate a significant body of evidence to evaluate results of these changes in technique and to develop optimal IOL designs and selection criteria for these specialized cataract patients.