Oxidative modification of tropomyosin and myocardial dysfunction following coronary microembolization.

AIMS: We addressed a potential mechanism of myocardial dysfunction following coronary microembolization at the level of myofibrillar proteins. METHODS AND RESULTS: Anaesthetized pigs underwent intracoronary infusion of microspheres. After 6 h, the microembolized areas (MEA) had decreased systolic wall thickening to 38 +/- 7% of baseline and a 2.62 +/- 0.40-fold increase in the formation of disulphide cross-bridges (DCB) in tropomyosin relative to that in remote areas. The impairment in contractile function correlated inversely with DCB formation (r = -0.68; P = 0.015) and was associated with increased TNF-alpha content. DCB formation was reflected by increased tropomyosin immunoreactivity and abolished in vitro by dithiothreitol. Ascorbic acid prevented contractile dysfunction as well as increased DCB and TNF-alpha. In anaesthetized dogs, 8 h after intracoronary microspheres infusion, contractile function was reduced to 8+/-10% of baseline and DCB in MEA was 1.48+/-0.12 higher than that in remote areas. In conscious dogs, 6 days after intracoronary microspheres infusion, myocardial function had returned to baseline and DCB was no longer different between remote and MEA. Again contractile function correlated inversely with DCB formation (r = -0.83; P = 0.005). CONCLUSION: Myofibrillar protein oxidation may represent a mechanistic link between inflammation and contractile dysfunction following coronary microembolization.     

A novel bioartificial liver with culture of porcine hepatocyte aggregates under simulated microgravity

An extracorporeal bioartificial liver device could provide vital support to patients suffering from acute liver failure. We designed a novel, customized bioreactor for use as a bioartificial liver (patent pending). The Innsbruck Bioartificial Liver (IBAL) contains aggregates of porcine hepatocytes grown under simulated microgravity. The culture vessel rotates around its longitudinal axis and is perfused by two independent circuits. The circuit responsible for exchange of plasma components with the patient consists of a dialysis tube winding spirally around the internal wall of the culture vessel. IBAL was evaluated in vitro. Viability tests showed sufficient viability of hepatocytes for up to 10 days. Cytologic examination of samples from the bioreactor showed liver cell aggregates. These were also examined by electron microscopy. A number of biochemical parameters were analyzed. In conclusion, cell culture is possible for at least 10 days in the IBAL system, organoid hepatocyte aggregates are formed and synthetic activity of the hepatocytes was demonstrated.     

Neurohumoral response and clinical effectiveness of continuous aortic flow augmentation in patients with decompensated heart failure

The increasing number of patients with progressive or exacerbated heart failure that is refractory to medical treatment necessitates the development of innovative cardiac assist devices. The aim of this study was to investigate whether a new percutaneously inserted system, which allows continuous aortic flow augmentation (CAFA), could be shown to be clinically effective with neurohormonal benefit in patients admitted with decompensated heart failure. Patients with exacerbations of chronic heart failure were recruited for the study. A percutaneous circulation assist device (Cancion system) promoting CAFA was implanted for up to 4 days in each patient. Clinical improvement was evaluated by measuring the clinical status according to the New York Heart Association (NYHA) classification and biochemical parameters including troponin and B-type natriuretic peptide (BNP) as markers of cardiac necrosis and cardiac overload; these parameters were measured before, during, and after CAFA treatment. The decrease in BNP was determined after implantation, reaching, on average, a maximum decrease of 57% at 72 h (P = 0.04). The neurohumoral response remained significant (P < 0.05) up to 120 h after implantation, with a decrease in BNP levels of 37%, on average, compared to baseline values. Troponin I did not show any significant change during mechanical assistance (P > 0.2). All patients had improved clinical status according to the NYHA classification, and the improvement lasted for more than 1 week. Percutaneous heart-assist devices promoting CAFA offer clinical improvement and a neurohumoral response, with a significant BNP reduction in severe exacerbation of chronic heart failure that is refractory to medical treatment.     

One Year’s Results from a Server-Based System for Performing Reject Analysis and Exposure Analysis in Computed Radiography

Rejected images represent both unnecessary radiation exposure to patients and inefficiency in the imaging operation. Rejected images are inherent to projection radiography, where patient positioning and alignment are integral components of image quality. Patient motion and artifacts unique to digital image receptor technology can result in rejected images also. We present a centralized, server-based solution for the collection, archival, and distribution of rejected image and exposure indicator data that automates the data collection process. Reject analysis program (RAP) and exposure indicator data were collected and analyzed during a 1-year period. RAP data were sorted both by reason for repetition and body part examined. Data were also stratified by clinical area for further investigation. The monthly composite reject rate for our institution fluctuated between 8% and 10%. Positioning errors were the main cause of repeated images (77.3%). Stratification of data by clinical area revealed that areas where computed radiography (CR) is seldom used suffer from higher reject rates than areas where it is used frequently. S values were log-normally distributed for examinations performed under either manual or automatic exposure control. The distributions were positively skewed and leptokurtic. S value decreases due to radiologic technology student rotations, and CR plate reader calibrations were observed. Our data demonstrate that reject analysis is still necessary and useful in the era of digital imaging. It is vital though that analysis be combined with exposure indicator analysis, as digital radiography is not self-policing in terms of exposure. When combined, the two programs are a powerful tool for quality assurance.     

Cold-Knife Conization versus Loop Excision: Histopathologic and Clinical Results of a Randomized Trial

Ninety patients with cervical intraepithelial neoplasia (CIN) were randomly assigned to loop excision (n = 38) or cold-knife conization (n = 52). All specimens were well evaluable at histology. The average width of the lesions at histology was 10.2 and 9.7 mm, respectively (ns). The average weight of the specimens was 2.6 and 5.6 g (P < 0.01) and the average depth was 9.2 and 15.8 mm (P < 0.01), respectively. The distance between the cervical resection margin and CIN was 14 mm after loop excision and 24 mm after cold-knife conizatiun (P < 0.06). The margins of the specimen were not clear of disease in 8 patients after loop excision and in 12 patients after conization (ns). Two patients after loop excision and in three patients after cold-knife conization had postoperative bleeding. The results suggest that, compared with cold-knife conization, loop excision removes less healthy tissue without reducing the chances for cure.     

Influence of GSTT1 and GSTM1 genotypes on sunburn sensitivity

Background: Exposure to sunlight may cause sunburn, skin cancer or phototoxic reactions to certain drugs such as Hypericum extract. All these are ultraviolet B (UVB)-mediated reactions which may be modulated by individual genetic susceptibility. UVB exposure results in oxidative stress. Many products of oxidative stress are detoxified by glutathione-S-transferases mu 1 (GSTM1) and theta 1 (GSTT1). Deletion polymorphisms (genotype *0/*0) of GSTM1 and GSTT1 occur in 50% and 20% of Caucasians, respectively. By affecting the individual ability to detoxify oxidative stress-related products, they may influence the severity of the cutaneous photoreaction. Methods: Minimal erythema doses (MED) of UVB irradiation on the skin were determined in 110 subjects who were selected according to their GSTT1 genotype (28 GSTT1*0/*0, 54 GSTT1*A/*0, and 28 GSTT1*A/*A). Genotypes were detected with novel polymerase chain reaction (PCR) assays that allow the differentiation between homozygous and heterozygous GSTT1 and GSTM1 deletions. Results: In the absence of GSTT1 enzyme, the susceptibility of individuals to UVB-induced inflammatory skin reactions increased significantly (p = 0.02, ANCOVA). ‘Gene-equivalents’ were calculated from the number of functional GSTM1 and GSTT1 alleles as a measure of the gene-dose. UVB sensitivity correlated with gene dose up to a threshold above which additional GSTT1 or GSTM1 alleles did not provide additional protection. Volunteers who were homozygously deficient in GSTT1 and GSTM1 were most sensitive to UVB. Interestingly, individuals with high GSTM1 gene-doses showed increased photosensitization after administration of Hypericum extract (St. John’s wort). Conclusion: Individuals harboring the *0/*0 genotype of GSTT1 and/or GSTM1 showed enhanced UVB-induced cutaneous damage. Moreover, GST genotypes modulated Hypericum-induced photosensitization.     

Electromagnetic field hazards involving adjustable shunt valves in hydrocephalus

OBJECT: Standard therapy for hydrocephalus involves shunts and valves, which are frequently adjustable. Because of increasing "electromagnetic smog" (for example, that generated by cellular phones), these valves are often exposed to electromagnetic fields. METHODS: Various magnetic fields were tested for their effects on two different kinds of adjustable valves. The minimum magnetic flux density affecting the adjustment of the valve was determined. Results were compared with magnetic fields found in contemporary everyday life. In homogeneous magnetic fields the adjustment of one valve (Sophysa model SM8) was changed at 5 mT, whereas the second valve (Codman Hakim model CM) was not affected. In nonhomogeneous fields the SM8 valve was affected at 25 mT and the CM valve at 15 mT. Thus, these valves may be affected by headphones and telephone receivers. Surroundings such as the Japanese magnetic suspension railway and the lead cabin of electrical railway engines, in which critical levels of magnetic flux may be present, may also affect adjustable valves. The high-frequency fields of cellular phones, however, have no effect on these valves. CONCLUSIONS: Every surgeon who implants these valves and every patient who receives them should know the possible hazards. The valve selection should be adapted to the environment of the patient. Devices with critical levels of electromagnetic flux that are used in the homes of patients should be replaced by ones with lower magnetic fields. The future construction of these valves should be modified in such a way that their adjustment requires a higher magnetic flux density, so that the valves become less sensitive to unwanted effects from environmental magnetic fields.