Biomechanical Analysis of Age-Dependent Changes in Fontan Power Loss.

The hemodynamics in Fontan patients with single ventricles rely on favorable flow and energetics, especially in the absence of a subpulmonary ventricle. Age-related changes in energetics for extracardiac and lateral tunnel Fontan procedures are not well understood. Vorticity (VOR) and viscous dissipation rate (VDR) are two descriptors that can provide insights into flow dynamics and dissipative areas in Fontan pathways, potentially contributing to power loss. This study examined power loss and its correlation with spatio-temporal flow descriptors (vorticity and VDR). Data from 414 Fontan patients were used to establish a relationship between the superior vena cava (SVC) to inferior vena cava (IVC) flow ratio and age. Computational flow modeling was conducted for both extracardiac conduits (ECC, n = 16) and lateral tunnels (LT, n = 25) at different caval inflow ratios of 2, 1, and 0.5 that corresponded with ages 3, 8, and 15+. In both cohorts, vorticity and VDR correlated well with PL, but ECC cohort exhibited a slightly stronger correlation for PL-VOR (>0.83) and PL-VDR (>0.89) than that for LT cohort (>0.76 and > 0.77, respectively) at all ages. Our data also suggested that absolute and indexed PL increase (p < 0.02) non-linearly as caval inflow changes with age and are highly patient-specific. Comparison of indexed power loss between our ECC and LT cohort showed that while ECC had a slightly higher median PL for all 3 caval inflow ratio examined (3.3, 8.3, 15.3) as opposed to (2.7, 7.6, 14.8), these differences were statistically non-significant. Lastly, there was a consistent rise in pressure gradient across the TCPC with age-related increase in IVC flows for both ECC and LT Fontan patient cohort. Our study provided hemodynamic insights into Fontan energetics and how they are impacted by age-dependent change in caval inflow. This workflow may help assess the long-term sustainability of the Fontan circulation and inform the design of more efficient Fontan conduits.

Impact of Age-related change in Caval Flow Ratio on Hepatic Flow Distribution in Fontan.

Background: The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac (EC) conduit or a lateral tunnel (LT) connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. Objective: The effect of age-related changes in caval inflows on HFD was evaluated using cardiac MRI (CMR) data and patient-specific computational fluid dynamics (CFD) modeling. Methods: SVC and IVC flow from 414 Fontan patients were collected to establish a relationship between SVC:IVC flow ratio and age. CFD modeling was performed in 60 (30 EC and 30 LT) patient models to quantify the HFD that corresponded to patient ages of 3, 8, and 15 years, respectively. Results: SVC:IVC flow ratio inverted at ∼8 years of age, indicating a clear shift to lower body flow predominance. Our data showed that variation of HFD in response to age-related changes in caval inflows (SVC:IVC = 2,1, and 0.5 corresponded to ages 3, 8, and 15+ respectively) was not significant for EC but statistically significant for LT cohorts. For all three caval inflow ratios, a positive correlation existed between the IVC flow distribution to both the lungs and the HFD. However, as the SVC:IVC ratio changed from 2→0.5 (age 3→15+), the correlation's strength decreased from 0.87→0.64, due to potential flow perturbation as IVC flow momentum increased. Conclusion: Our analysis provided quantitative insights into the impact of the changing caval inflows on Fontan's long-term HFD, highlighting the importance of including SVC:IVC variations over time to understand Fontan's long-term hemodynamics. These findings broaden our understanding of Fontan hemodynamics and patient outcomes. Clinical Perspective: With improvement in standard of care and management of single ventricle patients with Fontan physiology, the population of adults with Fontan circulation is increasing. Consequently, there is a clinical need to comprehend the impact of patient growth on Fontan hemodynamics. Using CMR data, we were able to quantify the relationship between changing caval inflows and somatic growth. We then used patient-specific computational flow modeling to quantify how this relationship affected the distribution of long-term hepatic flow in extracardiac and lateral tunnel Fontan types. Our findings demonstrated the significance of including SVC:IVC changes over time in CFD modeling to learn more about the long-term hemodynamics of Fontan. Fontan surgical approaches are increasingly planned and optimized using computational flow modeling. For a patient undergoing a Fontan procedure, the workflow presented in this study that takes into account the variations in Caval inflows over time can aid in predicting the long-term hemodynamics in a planned Fontan pathway.

Characterization of coagulase-negative staphylococci and macrococci isolated from cheese in Germany.

Cheese, especially ripened varieties, harbor a very complex and heterogeneous microbiota. In addition to the desired microorganisms (starter cultures) added during cheese production, potentially harmful bacteria may also enter the production chain. Regarding the latter, the focus of this study was on coagulase-negative staphylococci (CNS) and Macrococcuscaseolyticus. Both are known to harbor a variety of genes coding for antibiotic resistance, including mecA, mecB, mecC, and mecD. Coagulase-negative staphylococci or macrococci carrying such genes or other virulence factors should not be present in cheese. Cheese samples (101 in total) were collected from retail sources. Coagulase-negative staphylococci and M. caseolyticus were isolated utilizing selective agars, and species were identified by phenotypical tests and partial sequencing of the sodA gene. The results allowed identification of 53 CNS strains and 19 M. caseolyticus strains. Among the CNS, 11 isolates of Staphylococcus saprophyticus and one Staphylococcus epidermidis isolate were obtained. Both species are potential human pathogens and may thus adversely affect the safety of these food products. Screening for antimicrobial resistance was performed by application of disc diffusion tests, a gradient strip-test, and 14 different PCR tests. Evidence for methicillin resistance (by either positive disc diffusion assay for cefoxitin or by mec PCR) was found in CNS isolates and M. caseolyticus (9 isolates each). Regarding other virulence factors, no genetic determinants for coagulase or the most common staphylococcal enterotoxins sea, seb, sec, sed, and see were detected in any of the CNS or M. caseolyticus isolates by PCR testing. In conclusion, the presence of facultatively pathogenic CNS and carriers of genes for antibiotic resistance in both groups of microorganisms, especially mec genes, and the respective food safety issues need further evaluation and surveillance.

Characterization of coagulase-negative staphylococci from brining baths in Germany.

Brining is an important step in cheese making, and using brine baths for this purpose is common practice in German dairies. Time of brining, brine concentration, and composition of the complex and heterogeneous microbiota, including coagulase-negative staphylococci (CNS), contribute to the ripening and taste of cheese. As well as producing staphylococcal enterotoxins, some CNS show antibiotic resistance; therefore, we isolated 52 strains of presumptive CNS from cheese brines from 13 factories in Germany. Species identification by sodA gene sequencing revealed that 50 isolates were CNS: 31 Staphylococcus saprophyticus, 4 Staphylococcus carnosus, 4 Staphylococcus equorum, 3 Staphylococcus sciuri, 2 Staphylococcus hominis, and 2 Staphylococcus warneri. One isolate each was identified as Staphylococcus epidermidis, Staphylococcus pasteurii, Staphylococcus succinus, and Staphylococcus xylosus. Further subtyping of the Staph. saprophyticus isolates to the subspecies level revealed the presence of 6 Staph. saprophyticus ssp. saprophyticus. Using pulsed-field gel electrophoresis with the identified Staph. saprophyticus strains, 12 independent clones were identified, resulting in the exclusion of 18 strains from further testing. In 19 of the remaining 32 CNS isolates, resistance to antibiotics was observed. Resistance was found against oxacillin (17), penicillin (5), and cefoxitin (1). Four isolates expressed resistance to both oxacillin and penicillin. No resistance was found to enrofloxacin, tetracycline, gentamicin, or erythromycin. Then, PCR analysis for antibiotic resistance genes was performed for 22 different genes. Only genes blaZ and blaTEM were found in 7 isolates. These isolates were selected for challenge tests with different concentrations of lactic acid and NaCl to examine whether expression of antibiotic resistance was influenced by these stressors. An increase in the minimal inhibitory concentration from 0 to 2.0 µg/mL was seen for trimethoprim/sulfamethoxazole only in one isolate of Staph. saprophyticus at an increased lactic acid concentration. Finally, all isolates were tested for genetic determinants (entA, entB, entC, entD, and entE) of the most common staphylococcal enterotoxins; none of these genes were detected. We found no indication for unacceptable risks originating from the isolated CNS.

Fate of Listeria innocua during production and ripening of smeared hard cheese made from raw milk.

The fate of 2 different Listeria innocua strains was analyzed during the production and ripening of smeared raw milk Greyerzer cheese (Gruyère). These strains were used as surrogates for the pathogenic Listeria monocytogenes, as they are physiologically very similar. Bacterial cells were added to the cheese milk at levels of 105 cfu/mL. During the first 24 h of cheese making, the number of the test strains decreased to a level of below 102 cfu/g. Obviously, the cooking temperature of 56°C and the subsequent slight temperature decrease to 50°C within 70 min contributed to a distinct reduction of Listeria counts. The counts in the cheese cores did not exceed 103 cfu/g within 12 wk of cheese ripening and Listeria was not detectable after 24 wk. In contrast to the cores of the cheeses of the 4 batches in this study, their rinds always contained a high listerial load of approximately 106 to 108 cfu/g throughout the entire ripening period. The smeared surface showed an increase of pH to alkaline values, corresponding to smear microbiota development. Coryneforms and Staphylococcus counts were stable at >107 cfu/cm2 over 175 d, whereas yeast counts decreased to about 105 cfu/cm2 at the end of ripening. The study shows that the smear culture had no noticeable anti-listerial potential. When removing the rind or portioning such smeared cheese loaves with a cutting device, a postprocess contamination of the core might occur, thus presenting a major hygienic risk.

Inactivation of Mycobacterium bovis ssp. caprae in high-temperature, short-term pasteurized pilot-plant milk.

Experiments to determine the efficacy of high temperature, short time (HTST) pasteurization of milk in terms of inactivation of pathogenic microorganisms were mainly performed between 1930 and 1960. Among the target organisms were Mycobacterium bovis and Mycobacterium tuberculosis. As a result, the Codex Alimentarius prescribes that HTST treatment of milk should lead to a significant reduction of pathogenic microorganisms during milk pasteurization. Due to the development of improved methods for the detection of survivors and of more advanced heating technology, verification of this requirement seemed to be necessary. To address recent outbreaks of tuberculosis in cattle caused by M. bovis ssp. caprae (M. caprae) in the southern regions of Germany, this organism was tested and compared with M. bovis ssp. bovis (M. bovis). Experiments were performed in a pilot plant for HTST pasteurization of milk with 3 strains of M. caprae and 1 strain of M. bovis. In preliminary trials at a fixed holding time of 25 s, the temperature at which significant inactivation occurred was 62.5°C for all strains. To determine D-values (decimal reduction times) for the inactivation kinetics, the strains were tested at 65, 62.5, and 60°C at holding times of 16.5, 25, and 35 s. At 65°C, the D-values of all strains ranged from 6.8 to 7.8 s, and at 62.5°C, D-values ranged from 14.5 to 18.1 s. Low inactivation was observed at 60°C. When the low slope of the inactivation curve allowed calculation of a D-value, these ranged from 40.8 to 129.9 s. In terms of log10 reductions, the highest values for all strains were 4.1 to 4.9 log at 65°C, with a holding time of 35 s. The tested strains of M. caprae and M. bovis showed similar low resistance to heat. Standard HTST treatment should result in a high reduction of these organisms and thus the requirements of the Codex Alimentarius for inactivation of pathogens by this process are far exceeded.

Short communication: effect of homogenization on heat inactivation of Mycobacterium avium subspecies paratuberculosis in milk.

Mycobacterium avium ssp. paratuberculosis (MAP) can be present in cow milk and low numbers may survive high-temperature, short-time (HTST) pasteurization. Although HTST treatment leads to inactivation of at least 5 log10 cycles, it might become necessary to enhance the efficacy of HTST by additional treatments such as homogenization if the debate about the role of MAP in Crohn's disease of humans concludes that MAP is a zoonotic agent. This study aimed to determine whether disrupting the clumps of MAP in milk by homogenization during the heat treatment process would enhance the inactivation of MAP. We used HTST pasteurization in a continuous-flow pilot-plant pasteurizer and evaluated the effect of upstream, downstream, and in-hold homogenization on inactivation of MAP. Reduction of MAP at 72°C with a holding time of 28s was between 3.7 and 6.9 log10 cycles, with an overall mean of 5.5 log10 cycles. None of the 3 homogenization modes applied showed a statistically significant additional effect on the inactivation of MAP during HTST treatment.

Bifunctional silica nanoparticles for the exploration of biofilms of Pseudomonas aeruginosa.

Luminescent silica nanoparticles are frequently employed for biotechnology applications mainly because of their easy functionalization, photo-stability, and biocompatibility. Bifunctional silica nanoparticles (BSNPs) are described here as new efficient tools for investigating complex biological systems such as biofilms. Photoluminescence is brought about by the incorporation of a silylated ruthenium(II) complex. The surface properties of the silica particles were designed by reaction with amino-organosilanes, quaternary ammonium-organosilanes, carboxylate-organosilanes and hexamethyldisilazane. BSNPs were characterized extensively by DRIFT, (13)C and (29)Si solid state NMR, XPS, and photoluminescence. Zeta potential and contact angle measurements exhibited various surface properties (hydrophilic/hydrophobic balance and electric charge) according to the functional groups. Confocal laser scanning microscopy (CLSM) measurements showed that the spatial distribution of these nanoparticles inside a biofilm of Pseudomonas aeruginosa PAO1 depends more on their hydrophilic/hydrophobic characteristics than on their size. CLSM observations using two nanosized particles (25 and 68 nm) suggest that narrow diffusion paths exist through the extracellular polymeric substances matrix.

Short communication: heat resistance of Escherichia coli strains in raw milk at different subpasteurization conditions.

A commonly applied treatment of raw milk to reduce bacterial loads is the short-time application of heat at subpasteurization levels under continuous flow, generally referred to as thermization, because this method retains some of the beneficial properties of raw milk. In a previous study, Escherichia coli strains exhibiting increased thermotolerance were found, demanding investigations into their ability to survive thermization. Nine E. coli strains, including 4 Shiga toxin-producing E. coli (STEC) strains, were investigated for their reduction during a thermization treatment in raw milk using a pilot-plant pasteurizer to reflect typically applied commercial conditions. Six of the 9 E. coli strains, including the 4 STEC strains, were similarly inactivated at 60, 62.5, and 65°C, whereas increased thermotolerance was observed for 3 E. coli strains. All strains were reduced to <2 log10 at 60 and 62.5°C within 25s. At 65°C, 6 of 9 E. coli strains were reduced by at least 5 log10 after 25s, whereas at 67.5°C, such a reduction was observed for 8 strains. A much higher thermotolerance was found for E. coli strain FAM21805. For some E. coli strains, time-temperature combinations above 65°C were required to obtain a substantial reduction during a thermization treatment.

Fate of Shiga toxin-producing and generic Escherichia coli during production and ripening of semihard raw milk cheese.

The fate of 5 different Escherichia coli strains, including 3 Shiga toxin-producing E. coli (STEC) strains, was analyzed during the production and ripening of semihard raw milk cheese. The strains, which were previously isolated from raw milk cheese, were spiked into raw milk before cheese production at 2 different levels (approximately 10(1) and 10(3) cfu/mL, respectively). Two cheese types were produced, which differed in cooking temperatures (40 and 46°C). The cheeses were sampled during manufacture and the 16-wk ripening period. An increase in E. coli counts of approximately 3.5 log(10) cfu/g occurred from raw milk to fresh cheese at d 1, which was attributed to a concentration effect during cheese production and growth of the strains. During ripening over 16 wk, a slow, continuous decrease was observed for all strains. However, significant differences were found between the E. coli strains at the applied spiking levels, whereas the inactivation was similar in the 2 different cheese types. The 2 generic E. coli strains survived at higher counts than did the 3 STEC strains. Nevertheless, only 1 of the 3 STEC strains showed significantly weaker survival at both spiking levels and in both cheese types. Six of 16 cheeses made from raw milk at a low spiking level contained more than 10 cfu/g of STEC at the end of the 16-wk ripening process. After enrichment, STEC were detected in almost all cheeses at both spiking levels. Particularly because of the low infectious dose of highly pathogenic STEC, even low colony counts in raw milk cheese are a matter of concern.

Reservoir and routes of transmission of Enterobacter sakazakii (Cronobacter spp.) in a milk powder-producing plant.

Several outbreaks of Cronobacter spp. (Enterobacter sakazakii) have been described as food-borne illness in neonates and infants. Powdered infant formula has been identified as a source of infection, especially in hospital nurseries, where a bulk of formula nutrient is prepared for the whole day and instructions for preparation are not always followed correctly. Neonates who are underweight or immunosuppressed are especially at risk for an E. sakazakii infection. Considering that milk powder is the main ingredient of powdered infant formula, we analyzed the incidence and distribution of E. sakazakii in a milk powder-producing plant. We looked specifically at the spray-drying towers and roller dryers. Selected isolates from samples taken from the environment and final product were typed by pulsed-field gel electrophoresis to investigate the epidemiology of the organism within the production area of the plant. Seven pulsed-field gel electrophoresis types were detected in the spray-drying area, which presumably entered the plant through an aperture for process air and an improperly controlled roller shutter. Furthermore, textile filters for exhaust air of both the spray-drying towers were identified as internal reservoirs of the pathogen. For economic reasons, powder from the textile filters is reintroduced into the product flow; this can contaminate the final product. For the production of milk powder to be used as an ingredient of powdered infant formula, it was suggested to terminate the process of reintroducing the filtered powder into the product flow. A second transmission route was identified in the roller dryer section of the factory. It could be shown that contaminated milk concentrate could pass the process unheated, thus leading to a contamination of the product with E. sakazakii.

Using a similarity measure for credible classification.

This paper concerns classification by Boolean functions. We investigate the classification accuracy obtained by standard classification techniques on unseen points (elements of the domain, {0, 1}(n), for some n) that are similar, in particular senses, to the points that have been observed as training observations. Explicitly, we use a new measure of how similar a point x in {0, 1}(n) is to a set of such points to restrict the domain of points on which we offer a classification. For points sufficiently dissimilar, no classification is given. We report on experimental results which indicate that the classification accuracies obtained on the resulting restricted domains are better than those obtained without restriction. These experiments involve a number of standard data-sets and classification techniques. We also compare the classification accuracies with those obtained by restricting the domain on which classification is given by using the Hamming distance.

An inter-laboratory ring trial for the detection and isolation of Mycobacterium avium subsp. paratuberculosis from raw milk artificially contaminated with naturally infected faeces.

There is a need for standardised, robust, reproducible molecular and culture methods to achieve clarification of the inactivation of Mycobacterium avium subsp. paratuberculosis (Map), the causative microbial agent of Johne's disease, in (faecally) contaminated milk and other food products such as meat. This study assessed the performance of a commercially available Map DNA extraction kit for milk Adiapure and accompanying PCR detection kit Adiavet alongside 'in-house' molecular and culture methods in an inter-laboratory ring trial using raw milk spiked with Map-infected faeces. The combined Adiapure-Adiavet Map DNA extraction and detection kit consistently detected 30 copies of IS900 (equivalent to approximately 2 cells) ml(-1) raw milk, when used in four different laboratories. Improvements in sensitivity and ease of use for 'in-house' Map detection were observed when the Adiapure extraction kit was combined with 'in-house' detection assays. Detection by real-time PCR methods, using the commercial extraction and detection systems, resulted in an overall detection rate of 100%, 90%, 85% and 25% for respective Map concentrations of 300, 30, 3 and 0.3 copies of IS900ml(-1) raw milk. Map, at 300 copies of IS900 (equivalent to approximately 20 Map cells) ml(-1) raw milk, was recovered from all samples cultured in mycobacteria growth indicator tube (MGIT) medium, from 10 of 12 samples on Herrold's egg yolk medium (HEYM) and not recovered from any samples using BACTEC medium. In conclusion, the Adiapure DNA extraction kit allows for sensitive and easy detection of Map in raw milk. The extraction method can form a candidate part of essential methodology and real-time PCR can further increase the sensitivity of the detection method. Moreover, MGIT medium is promising for culture-dependent detection of Map from raw milk.

Logical analysis of diffuse large B-cell lymphomas.

OBJECTIVE: The goal of this study is to re-examine the oligonucleotide microarray dataset of Shipp et al., which contains the intensity levels of 6817 genes of 58 patients with diffuse large B-cell lymphoma (DLBCL) and 19 with follicular lymphoma (FL), by means of the combinatorics, optimisation, and logic-based methodology of logical analysis of data (LAD). The motivations for this new analysis included the previously demonstrated capabilities of LAD and its expected potential (1) to identify different informative genes than those discovered by conventional statistical methods, (2) to identify combinations of gene expression levels capable of characterizing different types of lymphoma, and (3) to assemble collections of such combinations that if considered jointly are capable of accurately distinguishing different types of lymphoma. METHODS AND MATERIALS: The central concept of LAD is a pattern or combinatorial biomarker, a concept that resembles a rule as used in decision tree methods. LAD is able to exhaustively generate the collection of all those patterns which satisfy certain quality constraints, through a systematic combinatorial process guided by clear optimization criteria. Then, based on a set covering approach, LAD aggregates the collection of patterns into classification models. In addition, LAD is able to use the information provided by large collections of patterns in order to extract subsets of variables, which collectively are able to distinguish between different types of disease. RESULTS: For the differential diagnosis of DLBCL versus FL, a model based on eight significant genes is constructed and shown to have a sensitivity of 94.7% and a specificity of 100% on the test set. For the prognosis of good versus poor outcome among the DLBCL patients, a model is constructed on another set consisting also of eight significant genes, and shown to have a sensitivity of 87.5% and a specificity of 90% on the test set. The genes selected by LAD also work well as a basis for other kinds of statistical analysis, indicating their robustness. CONCLUSION: These two models exhibit accuracies that compare favorably to those in the original study. In addition, the current study also provides a ranking by importance of the genes in the selected significant subsets as well as a library of dozens of combinatorial biomarkers (i.e. pairs or triplets of genes) that can serve as a source of mathematically generated, statistically significant research hypotheses in need of biological explanation.

HLA-B*3531, a hybrid of B35 and B61, implications for diagnostic approaches to alleles with complex ancestral compositions.

The serological characterization of allelic variants that have been generated by large-scale interallelic recombination events indicates which residues may be involved in the formation of epitopes crucial for serological recognition. The allelic product of HLA-B*3531 is composed of B35 in its alpha1 domain and of B61(40) in its alpha2 domain. Both specificities are only weakly detectable with available sera. Allelic products with 'mixed' serology also represent a challenge to DNA-based HLA typing methods, as only the sequence motif of one ancestral allele may be recognized. In this case the hidden specificity would not be considered in the matching process and might not be recognized as an antigen 'unacceptable' to the recipient.

Immunolocalization of cholecystokinin-2 receptors in rat gastric mucosa.

BACKGROUND: Gastrin exerts trophic effects on the gastric mucosa by mechanisms not yet completely elucidated. Our aim was to localize the cholecystokinin-2 (CCK2) receptor in epithelial cells of foetal and adult rat stomachs in order to determine the cell types that are directly affected by gastrin. METHODS: Gastric tissue was subjected to indirect double immunofluorescence staining with antiserum against the C-terminal decapeptide of the CCK2 receptor and antibodies against 5' bromo-2-deoxyuridine, which had been injected into the rats I h before they were killed, the acid pump H,K-ATPase, the membrane-cytoskeletal linker ezrin, pepsin/pepsinogen or histidine decarboxylase. RESULTS: Undifferentiated foetal gastric epithelial cells expressed CCK2 receptors, whereas stem cells of adult gastric glands did not exhibit immunoreactivity. However, other epithelial cells in the progenitor zone of adult gastric glands did express CCK2 receptors. Some of these cells were faintly stained for H,K-ATPase; pepsin/pepsinogen was also detected in this region. Parietal cells in the isthmus/pit region of the glands contained ezrin, and some showed weak immunoreactivity for the CCK2 receptor. As expected, enterochromaffin-like cells also expressed CCK2 receptors. CONCLUSION: Our findings are consistent with the hypothesis that a CCK2 receptor mediates direct effects of gastrin on gastric epithelial cells during both stomach organogenesis and adult life.

Long term results and morbidity of paraaortic compared with paraaortic and iliac adjuvant radiation in clinical stage I seminoma.

BACKGROUND: Radiotherapy is accepted as standard adjuvant treatment for low-stage seminoma and results in excellent survival rates. The optimal radiation field for stage I seminoma, however, is still being discussed. PATIENTS AND METHODS: In a retrospective study we evaluated long-term results concerning survival, relapse-pattern, and acute and chronic toxicity in patients receiving adjuvant radiotherapy of the paraaortic and ipsilateral iliac lymph nodes (hockey-stick, HS) versus radiotherapy of the paraaortic lymph nodes only (PA). From 1979-1997, 129 patients (median age 32 years) in clinical stage I received adjuvant radiotherapy. Eighty-seven patients were treated with 36 Gy to the HS field and 42 patients were treated with a median of 28 Gy to the PA field. RESULTS: With a median follow-up of 7.7 years (HS) and 5.2 years (PA) the relapse rate was 3.4% and 2.4%, respectively. There was no abdominal or pelvic recurrence in either group. Radiotherapy was well tolerated in both groups. No significant difference in acute or chronic toxicity was noted. However, lower gastrointestinal tract toxicities and myelotoxicities appeared less frequent in the PA group. Second malignancies only occurred in the HS group. Overall survival in the HS and PA group was 96.6% and 100%, respectively. No patient died of seminoma. CONCLUSION: With paraaortic radiotherapy only, long-term disease-specific survival was excellent. Decreased risk of acute toxicity and of second malignancies are potential benefits of the reduced radiation field.

Pegram v. Herdrich: On peritonitis, preemption, and the elusive goal of managed care accountability.

Managed care presents the paradox of organizations having real power over people's lives without there being clear or consistent means of ensuring accountability. In Pegram v. Herdrich, the United States Supreme Court struggled with whether "fiduciary duties" under the federal Employee Retirement Income Security Act (ERISA) could be used to counterbalance the incentives that HMOs have to deny necessary care. Given press coverage of the case, however, it was easy to get the impression that the managed care industry itself was on trial in Pegram. This report examines the political and legal forces underlying the dispute and analyzes the Supreme Court's unanimous rejection of the notion of federally imposed duties for HMOs. In the absence of ERISA fiduciary obligations, attention must now shift to developments in state tort law, the scope of federal ERISA preemption, and the prospect of legislative reform. The report concludes with an exploration of how the elusive goal of managed care accountability might be pursued in the wake of Pegram.

Induction of atrial tachycardia and fibrillation in the mouse heart.

BACKGROUND: Atrial tachycardia and fibrillation in humans may be partly consequent to vagal stimulation. Induction of fibrillation in the small heart is considered to be impossible due to lack of a critical mass of > 100-200 mm2. Even with the recent progression of the technology of in vivo and in vitro mouse electrophysiological studies, few reports describe atrial tachycardia or fibrillation in mice. The purpose of this study was to attempt provocation of atrial tachyarrhythmia in mice using transvenous pacing following cholinergic stimulation. METHODS AND RESULTS: In vivo electrophysiology studies were performed in 14 normal mice. A six-lead ECG was recorded from surface limb leads, and an octapolar electrode catheter was inserted via jugular vein cutdown approach for simultaneous atrial and ventricular endocardial recording and pacing. Atrial tachycardia and fibrillation were inducible in one mouse at baseline electrophysiology study and eleven of fourteen mice after carbamyl choline injection. The mean duration of atrial tachycardia was 126 +/- 384 s. The longest episode lasted 35 min and only terminated after atropine injection. Reinduction of atrial tachycardia after administration of atropine was not possible. CONCLUSION: Despite the small mass of the normal mouse atria, sustained atrial tachycardia and fibrillation can be easily and reproducibly inducible with endocardial pacing after cholinergic agonist administration. This finding may contribute to our understanding of the classical theories of arrhythmogenesis and critical substrates necessary for sustaining microreentrant circuits. The techniques of transcatheter parasympathetic agonist-mediated atrial tachycardia induction may be valuable in further murine electrophysiological studies, especially mutant models with potential atrial arrhythmia phenotypes.