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Peritoneal transport status influence on atherosclerosis/inflammation in CAPD patients.

OBJECTIVE: Peritoneal transport status is one of the main determinants of dialysis adequacy and dialysis-related complications in end-stage renal disease patients receiving continuous ambulatory peritoneal dialysis (CAPD). In this study we aimed to investigate the relationship between peritoneal transport characteristics and known promoters of atherosclerosis in a group of patients receiving CAPD for a minimum of 36 months. DESIGN AND PARTICIPANTS: We performed a cross-sectional study of a cohort of 84 patients with end-stage renal disease (37 men, 47 women; age, 44.0 +/- 15.7 years; dialysis duration, 40.3 +/- 8.1 months) who were receiving CAPD for minimum 36 months. Peritoneal transport characteristics were identified after a peritoneal equilibration test (PET) determined at the third month of CAPD using Dialysate/Plasma (D/P) reference values. Patients were classified according to one of four peritoneal transport types: high (H), high-average (HA), low-average (LA), and low (L). After PET, patients were grouped as high (H/HA group, n = 51) or low (L/LA group, n = 33) transporters. The patient groups' clinical and laboratory data before dialysis and after initiation of the CAPD were collected retrospectively. The patients' follow-up data were retrieved for the diagnosis of any atherosclerosis-related event after the initiation of CAPD. The following events were collected, including myocardial infarction, having been diagnosed as having coronary artery disease by angiography or myocardium scintigraphy, cerebrovascular accident, and development of clinically evident peripheral arterial disease. RESULTS: A comparison of follow-up data revealed that the H/HA transport characteristic was associated with lower albumin (P < .01), higher C-reactive protein (CRP) (P < .0001) levels, and higher recombinant human erythropoietin (rHuEPO) needs (P < .001) when compared with the L/LA type. During follow-up, 28 patients showed an atherosclerosis-related event. Twenty-two of these were in the H/HA group (43.1%), whereas only six were in the L/LA group (18.1%, P < .01). Reanalysis of 18 patients with atherosclerosis-related events and high CRP levels (> 10 mg/L) showed that 15 were in the H/HA and 3 were in the L/LA group. Sixty-eight percent of the H/HA patients with atherosclerosis and 50% of the L/LA patients with an atherosclerotic event also had chronic inflammation (P < .001). A Pearson correlation analysis showed that there was a positive correlation between D/P creatinine levels and 36-month mean CRP levels (r = 0.608, P < .0001), and a negative correlation between D/P creatinine levels and 36-month mean albumin levels (r = -0.299, P < .005). CONCLUSIONS: This study shows that the high transporter peritoneal membrane characteristic is a risk factor for inflammatory state in patients with end-stage renal disease. High-transporter patients are at an increased risk of atherosclerosis when compared with their low-transporter counterparts through chronic inflammation.

Adult↗

Organ procurement--strategies to optimize donor availability.

Increasing donor availability for organ transplantation requires attention to factors that are potentially modifiable. The potential pool of available organs can theoretically be enlarged by considering new sources of organs, including non-beating heart donors, live donor lobar transplants, xenotransplants, and in vitro organ culture. Increased utilization of the current pool of organs can be achieved by creating a system that identifies, considers, and optimizes all possible donors. Although protocols have been drawn up regarding general and specifically lung donor acceptance criteria, many of these can be now recognized as unduly conservative and without a proven clinical basis. Careful reanalysis of these acceptance criteria and active donor management can be balanced against the particular circumstance of an individual potential recipient to increase lung transplantation rates.

Journal Article↗

[Attachment characteristics and psychotherapy outcome following inpatient psychodynamic group treatment].

Within a reanalysis of the "Kiel Group Psychotherapy Study", the videorecorded intake interviews of 34 patients were analyzed using the adult attachment prototype rating. Three subgroups, differentiated according to their attachment patterns (avoidant, ambivalent, mixed insecure) differed marginally with respect to their treatment success, with ambivalent patients showing the most positive outcome (escpecially with regard to symptom- and self-system-related outcome criteria). In addition, there were indications for a differential assessment of group related therapeutic factors by the subgroups. Patients with an avoidant attachment pattern evaluated group-related factors such as cohesion and altruism as least helpful. The study is discussed in relation to existing findings on the significance of attachment related variables for the indication and prognosis of psychotherapy.

Adult↗

[The sequential traumatisation of a Sinti-child Holocaust-survivor].

The subject of this case-report is the life-history, nosogenesis and history of compensation claims of a 64-years old Sinti-woman, who survived Nazi-persecution and WWII as a child. She and her mother spent 3 years in a concentration camp. At the end of the war she witnessed her mothers death. Her life is characterised by psychosomatic symptoms, disorders of psychosexual development, including infertility, and a chronic Post Traumatic Stress Disorder. The non-treated course of the Holocaust survivor syndrom, described by Niederland, which was mostly denied in Germany, could be now shown by detailed exploration and the reanalysis of former expert reports of her symptoms. Furthermore, this case report presents the internationally described characteristics of long-term effects in children that have survived the Holocaust. These symptoms are typical of cases that were not been treated throughout life. The former lack of acceptance in Germany of these long-term effects has - like in this and other cases - lead to development into a chronic disorder.

Compensation and Redress↗

[Perceptions of quality of life in schizophrenic patients].

BACKGROUND: Subjective quality of life in schizophrenic persons is a commonly applied indicator in outcomes research. However, it remains unclear whether the content of the construct is adequately represented from the patients' point of view, and whether changing representations in the course of illness should be accounted for in terms of re-prioritization of the concept. PURPOSE: Identification of specific perceptions of quality of life (QoL) of schizophrenic persons and analysis of changes of those perceptions with increasing chronicity. METHODS: The present study is a reanalysis of responses to a short, structured, open-ended interview taken from different studies in social psychiatry research. 403 schizophrenic persons from different care settings (psychiatric hospitals, community based institutions) as well as 178 mentally healthy persons were interviewed with regard to positive and negative aspects of their QoL. A qualitative content-analysis resulted in a comprehensive hierarchy of categories. The proportion of persons who mentioned a respective QoL-aspect was compared. Relationship between chronicity and perceptions of QoL were analysed by means of chi (2)(trend)-tests. RESULTS: Schizophrenic persons mentioned about one fewer QoL domain compared to the mentally healthy (8.3 (sd = 2.8) vs. 9.6 (sd = 2.0), P < 0.001). They had fewer assertions on work aspects as well as in social domains (family, social relationships, partnership). The proportion of statements in social domains was negatively associated with the degree of chronicity. Among other things the schizophrenic persons showed a higher proportion of statements regarding "oral needs" (food, drinking-related statements, smoking) and (problems with) daily activities; both domains were associated with the degree of chronicity. DISCUSSION: Differences between schizophrenic and mentally healthy persons in their perceptions of QoL were more pronounced with increasing chronicity. It remains unclear at which point in the course of illness this is best understood in terms of re-prioritization or even re-conceptualization of the entire concept.

Adult↗

[Vocational therapy in schizophrenia: effects only with some patients and with which patients?].

OBJECTIVES: In a previous study the effectiveness of vocational therapy was evaluated using the Osnabrück Profile of Working Abilities (O-AFP). No or only minor effects were detected. The goal of this reanalysis is to identify distinct responder groups. METHODS: Hierarchical cluster analysis of O-AFP-scores before and after treatment, anovas, t-statistics as well as regression and discriminant analyses were applied to specify the clusters. RESULTS: For each of the O-AFP-scales (Learning Ability, Social Communication Ability, Adaptation) three subgroups different in level and slope of abilities could be identified. Improvements with medium to high effect sizes were detected for Social Communication Ability (34 %) and Learning Ability (14 % of the patients), deterioration was found in 30 % of the patients for Adaptation. Subgroups could be described with the help of symptomatology. Further variables and subgroup membership could be predicted above chance by discriminant and regression analysis. CONCLUSION: Targeted and more appropriate design of vocational therapy seems necessary.

Adult↗

[Calculation by Supprian of the phase calendar of endogenous depressions--a statistical artifact?].

According to Supprian (10, 13, 14) the postulate of internal desynchronisation of drive and mood is a necessary condition for the estimation of the time-structure of endogenous depression. This hypothesis could not be substantiated in a longitudinal study of four depressive patients. A subsequent reanalysis of data, published by Supprian (13) contradicts the central postulate of internal desynchronisation. A critical review of other publications (10, 11, 14) suggests the assumption that the statistical analysis of this data might be erroneous too.

Circadian Rhythm↗

Has the outcome for extremely low gestational age (ELGA) infants improved following recent advances in neonatal intensive care?

The objectives of this paper are to examine (a) the survival of extremely low-gestational-age (ELGA) infants born at 23-28 weeks' gestational age (GA) and (b) the neurodevelopmental outcome at 18 months corrected age for those born at 23-25 weeks' GA during 1991-1993, when antenatal steroids, surfactant, and dexamethasone for bronchopulmonary dysplasia had become accepted treatments; and to compare with an earlier (1983-1989), previously published large cohort (in a presurfactant era) from our institution. Perinatal and neonatal data on all births delivered at 23-28 weeks' GA at British Columbia's tertiary perinatal center were analyzed for survival rates by GA. Survivors of those born at 23-25 weeks' GA underwent neurodevelopmental assessment at a corrected chronological age of 18 months. The recent cohort (n = 333) of live birth infants, compared to the earlier cohort (n = 911 ) showed a trend toward an overall improved survival to discharge (72 vs. 65%, p = 0.06). Further analysis showed that improved survival was seen only in 26- to 28-week GA infants (86 vs. 76%, p = 0.01), but not in 23- to 25-week GA infants (44 vs. 44%, p = 0.9), even when adjusted for gender or twin births. In addition, the incidence of major impairment at 18 months (36% in both periods) remained high. Reanalysis of 24- to 25-week GA infants again showed no evidence of improved survival (53 vs. 50%) or improved outcome at 18 months (major handicap rate 32%; vs. 34%). Survival rates improved for 26- to 28-week GA infants, but the survival rate and incidence of major impairment had not improved for of 23- to 25-week GA infants.

Age Factors↗

Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis.

Recent magnetic resonance imaging (MRI) and magnetic resonance spectroscopic (MRS) techniques have focused the attention of the multiple sclerosis (MS) research community on reanalysis of classic pathological approaches that have suggested significant axonal injury in this demyelinating disease. There now is abundant evidence from animal work that substantial "innocent bystander" damage to axons can occur with central nervous system (CNS) inflammation. Given the close interactions between axons and glia, it is no surprise that glial damage leads to secondary axonal changes. MRI, MRS, and MRS imaging studies have emphasized that axonal loss or damage in MS can be both substantial and early. The dynamic observations that are allowed by these noninvasive measures of pathology have demonstrated direct correlations between these axonal changes and disability, making a compelling case for increased emphasis on finding treatments of MS that may limit damage to CNS axons or salvage injured axons.

Atrophy↗

The National Cancer Institute audit of the National Surgical Adjuvant Breast and Bowel Project Protocol B-06.

BACKGROUND: The National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-06, a clinical trial sponsored by the National Cancer Institute (NCI), has provided evidence of the value of lumpectomy and breast irradiation for treating women with breast cancer in an early stage. Publicity generated by the discovery that the study included fraudulent data on patients enrolled by St. Luc Hospital in Montreal aroused concern about the overall accuracy of the data and conclusions. To address this concern, the NCI conducted an audit of other participating institutions. METHODS: In 1994, data on 1554 of the 1809 randomized patients (85.9 percent) enrolled by centers other than St. Luc Hospital were audited at 37 clinical sites in North America. The audit included data on eligibility, survival, disease-free survival, the length of time to a recurrence of cancer in the ipsilateral breast, and documentation of signed informed consent. RESULTS: End points were assessed for all 1554 patients, and eligibility was assessed for 1507 patients; 47 patients were excluded because their forms were not complete or not returned. A total of 1429 patients had their eligibility status verified. Of a total of 7770 data points examined with respect to the number of positive nodes at base line, treatment characteristics, first events (excluding death), recurrence of cancer in the ipsilateral breast, and survival, 7577 (97.5 percent) were verified, 123 (1.6 percent) could not be verified, and 70 (0.9 percent) were discrepant with the NSABP file. Of the 1554 patients, 1340 (86.2 percent) had all audited items (including eligibility) verified, 69 (4.4 percent) had at least one discrepant item, and 113 (7.3 percent) had at least one unverified item (as a result of missing or incomplete data); 32 (2.1 percent) were not assessed for eligibility but had no other discrepant or unverifiable items. Written informed consent was documented for 1098 patients before surgery and 210 after surgery; no date appeared on the signed form for 137. The informed-consent status was not verified for 71 patients and could not be determined for 38. The rates of verification of end-point data and documentation of written informed consent were similar among the total-mastectomy group, the lumpectomy group, and the group treated by lumpectomy and breast irradiation. CONCLUSIONS: The audit confirms the adequacy of the data on which the reanalysis of Protocol B-06 and the results after 12 years of follow-up are based.

Breast Neoplasms↗

An economic evaluation of activated protein C treatment for severe sepsis.

BACKGROUND: Recombinant human activated protein C was shown in the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study to reduce mortality among patients with severe sepsis. A post hoc reanalysis by the Food and Drug Administration (FDA) of data from this study suggested that the reduction in mortality was restricted to patients with Acute Physiology and Chronic Health Evaluation (APACHE II) scores of 25 or more. METHODS: We estimated the cost effectiveness of activated protein C as compared with conventional care for patients with severe sepsis. We performed an economic analysis involving all patients, as well as analyses of subgroups defined according to age and severity of illness. The probabilities of transition between clinical states and the estimates of resource use were derived from a population-based cohort of patients with severe sepsis. We used data on the effectiveness of activated protein C from the PROWESS study and analyses by the FDA. RESULTS: The cost per life-year gained by treating all patients with activated protein C was $27,936. It was more cost effective to treat patients with an APACHE II score of 25 or more ($24,484 per life-year gained) than those with a lower APACHE II score ($35,632 per life-year gained). The cost effectiveness of treating patients with an APACHE II score of 24 or less increased to $575,054 per life-year gained when the FDA's estimates of effectiveness were considered. For patients with an APACHE II score of 25 or more, the cost per life-year gained increased with age ($16,309 for patients less than 40 years of age; $28,100 for those 80 years of age or older). CONCLUSIONS: Activated protein C is relatively cost effective when targeted to patients with severe sepsis, greater severity of illness (an APACHE II score of 25 or more), and a reasonable life expectancy if they survive the episode of sepsis. Further research is needed to determine the cost effectiveness of activated protein C for patients with sepsis and less severe illness.

APACHE↗

On the structure of the FeF3 molecule.

With increasing computational possibilities the question of critical comparison of computed results with experimental data gains importance. Differences in the physical meaning of parameters determined by different techniques and the uncertainties of both experimental and computed parameters need to be scrutinized in such comparisons. In view of a recent computational study [V. G. Solomonik, J. F. Stanton, and J. E. Boggs, J. Chem. Phys.122, 094322 (2005)] of the FeF(3) molecule, its earlier electron-diffraction data were reanalyzed and compared with the theoretical results. Based on this reanalysis we can rule out the suggested source of the slight discrepancy between the computed and measured bond lengths.

Journal Article↗

n-alkanes on Pt(111) and on C(0001)Pt(111): chain length dependence of kinetic desorption parameters.

We have measured the desorption of seven small n-alkanes (C(N)H(2N+2), N=1-4,6,8,10) from the Pt(111) and C(0001) surfaces by temperature programed desorption. We compare these results to our recent study of the desorption kinetics of these molecules on MgO(100) [J. Chem. Phys. 122, 164708 (2005)]. There we showed an increase in the desorption preexponential factor by several orders of magnitude with increasing n-alkane chain length and a linear desorption energy scaling with a small y-intercept value. We suggest that the significant increase in desorption prefactor with chain length is not particular to the MgO(100) surface, but is a general effect for desorption of the small n-alkanes. This argument is supported by statistical mechanical arguments for the increase in the entropy gain of the molecules upon desorption. In this work, we demonstrate that this hypothesis holds true on both a metal surface and a graphite surface. We observe an increase in prefactor by five orders of magnitude over the range of n-alkane chain lengths studied here. On each surface, the desorption energies of the n-alkanes are found to increase linearly with the molecule chain length and have a small y-intercept value. Prior results of other groups have yielded a linear desorption energy scaling with chain length that has unphysically large y-intercept values. We demonstrate that by allowing the prefactor to increase according to our model, a reanalysis of their data resolves this y-intercept problem to some degree.

Journal Article↗

Spectral envelope and context effects in the tritone paradox.

In previous studies of the 'tritone paradox' Deutsch has suggested that, when listeners are presented with pairs of octave-complex tones that are equal in average log frequency but differ in chroma by 6 semitones (a tritone), they perceive the direction of the chroma difference according to an individual pitch-class template. However, it has also been found that the perceived direction changes for many listeners when the spectral envelope of the tones is shifted along the frequency axis. Reanalysis of these data indicates a strong tendency to perceive the pitch class corresponding to the frequency on which the spectral envelope is centered as subjectively lowest. In experiment 1 this spectral-envelope effect was replicated with tone pairs presented in isolation, at the rate of one a day, which rules out artifacts of test format. In experiment 2, involving another context-free format, envelope center frequency was varied over a wide range and it was shown that some individuals are totally envelope dependent, whereas others rely more on pitch class, and yet others show mixed patterns. Experiment 3 demonstrated that listeners' judgments of tritone pairs can be swayed easily by preceding context. Finally, experiment 4 showed that strong envelope effects are also obtained with Deutsch's own tritone test (issued on CD). The subjective relative pitch height of octave-complex tones thus depends on several competing factors, only one of which is pitch class.

Female↗

Fluorescence-activated cell sorting (FACS) of Drosophila hemocytes reveals important functional similarities to mammalian leukocytes.

Drosophila is a powerful model for molecular studies of hematopoiesis and innate immunity. However, its use for functional cellular studies remains hampered by the lack of single-cell assays for hemocytes (blood cells). Here we introduce a generic method combining fluorescence-activated cell sorting and nonantibody probes that enables the selective gating of live Drosophila hemocytes from the lymph glands (larval hematopoietic organ) or hemolymph (blood equivalent). Gated live hemocytes are analyzed and sorted at will based on precise quantitation of fluorescence levels originating from metabolic indicators, lectins, reporters (GFP and beta-galactosidase) and antibodies. With this approach, we discriminate and sort plasmatocytes, the major hemocyte subset, from lamellocytes, an activated subset present in gain-of-function mutants of the Janus kinase and Toll pathways. We also illustrate how important, evolutionarily conserved, blood-cell-regulatory molecules, such as calcium and glutathione, can be studied functionally within hemocytes. Finally, we report an in vivo transfer of sorted live hemocytes and their successful reanalysis on retrieval from single hosts. This generic and versatile fluorescence-activated cell sorting approach for hemocyte detection, analysis, and sorting, which is efficient down to one animal, should critically enhance in vivo and ex vivo hemocyte studies in Drosophila and other species, notably mosquitoes.

Animals↗

Protein tolerance to random amino acid change.

Mutagenesis of protein-encoding sequences occurs ubiquitously; it enables evolution, accumulates during aging, and is associated with disease. Many biotechnological methods exploit random mutations to evolve novel proteins. To quantitate protein tolerance to random change, it is vital to understand the probability that a random amino acid replacement will lead to a protein's functional inactivation. We define this probability as the "x factor." Here, we develop a broadly applicable approach to calculate x factors and demonstrate this method using the human DNA repair enzyme 3-methyladenine DNA glycosylase (AAG). Three gene-wide mutagenesis libraries were created, each with 10(5) diversity and averaging 2.2, 4.6, and 6.2 random amino acid changes per mutant. After determining the percentage of functional mutants in each library using high-stringency selection (>19,000-fold), the x factor was found to be 34% +/- 6%. Remarkably, reanalysis of data from studies of diverse proteins reveals similar inactivation probabilities. To delineate the nature of tolerated amino acid substitutions, we sequenced 244 surviving AAG mutants. The 920 tolerated substitutions were characterized by substitutability index and mapped onto the AAG primary, secondary, and known tertiary structures. Evolutionarily conserved residues show low substitutability indices. In AAG, beta strands are on average less substitutable than alpha helices; and surface loops that are not involved in DNA binding are the most substitutable. Our results are relevant to such diverse topics as applied molecular evolution, the rate of introduction of deleterious alleles into genomes in evolutionary history, and organisms' tolerance of mutational burden.

Amino Acid Substitution↗

Morphological homoplasy, life history evolution, and historical biogeography of plethodontid salamanders inferred from complete mitochondrial genomes.

The evolutionary history of the largest salamander family (Plethodontidae) is characterized by extreme morphological homoplasy. Analysis of the mechanisms generating such homoplasy requires an independent molecular phylogeny. To this end, we sequenced 24 complete mitochondrial genomes (22 plethodontids and two outgroup taxa), added data for three species from GenBank, and performed partitioned and unpartitioned Bayesian, maximum likelihood, and maximum parsimony phylogenetic analyses. We explored four dataset partitioning strategies to account for evolutionary process heterogeneity among genes and codon positions, all of which yielded increased model likelihoods and decreased numbers of supported nodes in the topologies (Bayesian posterior probability >0.95) relative to the unpartitioned analysis. Our phylogenetic analyses yielded congruent trees that contrast with the traditional morphology-based taxonomy; the monophyly of three of four major groups is rejected. Reanalysis of current hypotheses in light of these evolutionary relationships suggests that (i) a larval life history stage reevolved from a direct-developing ancestor multiple times; (ii) there is no phylogenetic support for the "Out of Appalachia" hypothesis of plethodontid origins; and (iii) novel scenarios must be reconstructed for the convergent evolution of projectile tongues, reduction in toe number, and specialization for defensive tail loss. Some of these scenarios imply morphological transformation series that proceed in the opposite direction than was previously thought. In addition, they suggest surprising evolutionary lability in traits previously interpreted to be conservative.

Animals↗

Genomic analysis of Drosophila chromosome underreplication reveals a link between replication control and transcriptional territories.

In Drosophila polytene chromosomes, most late-replicating regions remain underreplicated. A loss-of-function mutant of the suppressor of underreplication [Su(UR)] gene suppresses underreplication (UR), whereas extra copies of this gene enhance the level and number of regions showing UR. By combining DNA microarray analysis with manipulation of the number of Su(UR) gene copies, we achieved genomic-scale molecular identification of 1,036 genes that are arranged in clusters located in 52 UR chromosomal regions. These regions overlap extensively (96%) but are not completely identical with late-replicating regions of mitotically dividing Kc cells in culture. Reanalysis of published gene expression profiles revealed that genomic regions defined by replication properties include clusters of coordinately expressed genes. Genomic regions that are UR in polytene chromosomes and late replicated in Kc cell chromosomes show a particularly common association with transcriptional territories that are expressed in testis/males but not ovary/females or embryos. An attractive hypothesis for future testing is that factors involved in replication control, such as SU(UR), may interact physically with those involved in epigenetic silencing of transcription territories.

Animals↗