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.     

Cholinergic modulation of the acoustic startle response in the caudal pontine reticular nucleus of the rat.

The startle response is a useful behavioural model to assess drug effects on sensorimotor information processing in the mammalian central nervous system. Prepulse inhibition of the acoustic startle response in rats is an operational measure for sensorimotor gating mechanisms which may be necessary for attention and response selection. The caudal pontine reticular nucleus is a key element of the pathway that mediates the acoustic startle response and receives an inhibitory cholinergic projection that might be important for prepulse inhibition. The present study tested whether prepulse inhibition of acoustic startle is modulated by microinfusions of the muscarinic/nicotinic acetylcholine receptor agonist carbachol and of the muscarinic acetylcholine receptor antagonist scopolamine. Carbachol (0-40 nmol/0.5 microl) dose dependently attenuated startle and enhanced prepulse inhibition. Scopolamine (0-40 nmol/0.5 microl) dose-dependently enhanced startle and reduced prepulse inhibition at a dose of 10 nmol. Scopolamine (40 nmol) also increased the spontaneous motor activity of the rats. These findings lend support to the hypothesis that muscarinic acetylcholine receptors in the caudal pontine reticular nucleus inhibit the acoustic startle response and are involved in the mediation of prepulse inhibition of startle.     

Upregulation of the cardiac bradykinin B2 receptors after myocardial infarction

An increase in myocardial bradykinin (BK) might be a mechanism to protect the heart during acute myocardial infarction (MI). To characterize the regulation of the myocardial B2 receptor during MI, we studied the expression of this BK receptor in the right ventricle (RV), left ventricle (LV) and myocardial septum (S) 24 h after left coronary ligation. Experiments were performed in male Wistar Kyoto rats (n = 10) and compared with sham operated animals (n = 6). After total RNA extraction, the myocardial B2-receptor expression was analyzed by a RNase protection assay (n = 6), using a specific probe from the coding region of the receptor gene. After 24 h, rats with MI were normotensive and showed an impaired left ventricular function. The B2-receptor expression of the LV of these rats was significantly elevated (2.3-fold) compared to sham operated rats. Furthermore, we found a dramatic upregulation of the B2 receptor in the RV (7.8-fold) and a dramatic expression of B2 receptor mRNA in S of infarcted hearts, whereas in the S of sham operated rats no B2 receptor expression could be detected. Our data show clearly that the described increase in BK during myocardial ischemia is accompanied by an elevated B2-receptor expression in the infarcted and non-infarcted parts of cardiac ventricles.     

Physicochemical Characterization of Protein-Free Low Density Lipoprotein Models and Influence of Drug Loading

Purpose. Drug free and drug loaded protein-free low density lipoprotein (LDL) models consisting mainly of phospholipids, cholesterol, cholesterol esters, and triglycerides in ratios found for physiological LDL have been prepared. Their physicochemical characteristics were compared with those of physiological LDL. Methods. Different characterization methods were used: photon correlation spectroscopy, transmission electron microscopy, X-ray solution scattering, and ¹H nuclear magnetic resonance spectroscopy (NMR). Results. Particle sizes are highly dependent on the preparation method and in particular on the homogenization conditions. Electron microscopy indicates that the size distributions of model systems are much broader than those of physiological LDL. The X-ray solution scattering patterns of the model systems display a temperature dependent maximum near 3.8 nm similar to that found in the patterns of physiological LDL. NMR indicates a comparable mobility of the lipid molecules in model particles and in physiological LDL. The influence of drug loading is similar to that found earlier for physiological LDL. In particular, the incorporation of the anti-cancer drug WB 4291 seems to have a fluidizing effect on the lipids in the core region of the particles. Conclusions. The preparation method of LDL model systems is of crucial importance as only the solvent evaporation method yielded systems in the size range of physiological LDL with acceptable high lipid concentrations. The fluidizing influence of temperature and drug incorporation (WB 4291) may be a disadvantage in drug targeting.     

Reliability of the International Prostate Symptom Score in the Assessment of Patients With Lower Urinary Tract Symptoms and/or Benign Prostatic Hyperplasia

Purpose

The reliability of the International Prostate Symptom Score (I-PSS) was tested in patients with lower urinary tract symptoms and/or benign prostatic hyperplasia.

Materials and Methods

A total of 71 consecutive men with benign prostatic hyperplasia and/or lower urinary tract symptoms was asked to complete the I-PSS at baseline and 8 weeks later. At the second visit the physician also completed the I-PSS according to the complaints of the patient. Variability between both scores was evaluated by calculation of duplo errors and results were compared to the clinical data.

Results

A considerable variability existed between the I-PSS results obtained at baseline and 8 weeks. The duplo error was 4.3. In a regression analysis of I-PSS, including all clinical parameters, only free flow had some predictive value for I-PSS outcomes.

Conclusions

It is important to consider the variability of the I-PSS score when making decisions concerning treatment.     

Ureteral Replacement with Reconfigured Colon Substitute

Purpose

Upper ureteral defects are often too extensive to repair by direct anastomosis or with use of a bladder flap. Ureteral substitution may be the only remaining alternative to restoring urinary drainage from the kidney to the bladder. This effect is usually achieved by interposing a segment of small bowel between the proximal collecting system and bladder. If ileum is not available other substitution alternatives must be sought.

Materials and Methods

We report a new technique in which a tube constructed from a small piece of ascending colon was used to replace a large ureteral defect.

Results

Excellent short-term results were achieved by replacing the strictured ureteral segment with a reconfigured colon segment as shown by symptomatic and radiographic improvement.

Conclusions

A reconfigured colon segment can be used for ureteral reconstruction in the patient with limited alternatives. This tube has several advantages for ureteral reconstruction over ileal segments.     

Bronchoscopic findings in post-obstructive pulmonary oedema

Purpose

To present the first photographed bronchoscopic findings associated with negative pressure pulmonary oedema (NPPE).

Clinical features

A previously healthy patient underwent anterior C₃–C₄ disc removal and arthrodesis. Following tracheal extubation he developed acute respiratory distress manifested as stridor, tachypnoea, restlessness, and desaturation. Once the trachea was reintubated, he displayed the classic findings of pulmonary oedema. Bronchoscopy was performed to confirm tracheal tube position and to rule out tracheal injury secondary to surgical manipulation. Diffuse punctate haemorrhages were noted throughout the visualised tracheobronchial tree.

Conclusion

We believe that these haemorrhages represent disruption of the bronchial vasculature and may contribute to the clinical presentation of NPPE.