REEXAMINING SCHREBER THROUGH THE LENS OF A PRESENT-DAY CASE: FANTASIES OF DEATH, REBIRTH, AND GENDER TRANSFORMATION.

In the history of psychoanalysis, the Schreber case has long been a source of controversy. Speculations about Schreber have abounded essentially because none of the speculators, including Freud (), has been constrained by the reality of interactive dynamics with Schreber on the couch. This author contends, however, that knowing someone analytically must involve the transference experience. He presents the case of Z, a middle-aged patient of his who described a fantasy that was uncannily similar to Schreber's, permitting a present-day reexamination of the original case, as well as ongoing speculations that include the way in which live clinical material can interact with the reading of a historical document.

Association of Systemic Sclerosis With a Unique Colonic Microbial Consortium.

OBJECTIVE: To compare colonic microbial composition in systemic sclerosis (SSc) patients and healthy controls and to determine whether certain microbial genera are associated with gastrointestinal (GI) tract symptoms in patients with SSc. METHODS: Healthy controls were age- and sex-matched (1:1) with adult SSc patients. Cecum and sigmoid mucosal lavage samples were obtained during colonoscopy. The microbiota in these samples were determined by Illumina HiSeq 2000 16S sequencing, and operational taxonomic units were selected. Linear discriminant analysis effect size was used to identify the genera that showed differential expression in SSc patients versus controls. Differential expression analysis for sequence count data was used to identify specific genera associated with GI tract symptoms. RESULTS: Among 17 patients with SSc (88% female; median age 52.1 years), the mean ± SD total GI Tract 2.0 score was 0.7 ± 0.6. Principal coordinate analysis illustrated significant differences in microbial communities in the cecum and sigmoid regions in SSc patients versus healthy controls (both P = 0.001). Similar to the findings in inflammatory disease states, SSc patients had decreased levels of commensal bacteria, such as Faecalibacterium and Clostridium, and increased levels of pathobiont bacteria, such as Fusobacterium and γ-Proteobacteria, compared with healthy controls. Bifidobacterium and Lactobacillus, which are typically reduced under conditions of inflammation, were also increased in abundance in patients with SSc. In SSc patients with moderate/severe GI tract symptoms, the abundance of Bacteroides fragilis was decreased, and that of Fusobacterium was increased, compared with patients who had no or mild symptoms. CONCLUSION: This study demonstrates a distinct colonic microbial signature in SSc patients compared with healthy controls. This unique ecologic change may perpetuate immunologic aberrations and contribute to clinical manifestations of SSc.

Microgeographic Proteomic Networks of the Human Colonic Mucosa and Their Association With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Interactions between mucosal cell types, environmental stressors, and intestinal microbiota contribute to pathogenesis in inflammatory bowel disease (IBD). Here, we applied metaproteomics of the mucosal-luminal interface to study the disease-related biology of the human colonic mucosa. METHODS: We recruited a discovery cohort of 51 IBD and non-IBD subjects endoscopically sampled by mucosal lavage at 6 colonic regions, and a validation cohort of 38 no-IBD subjects. Metaproteome data sets were produced for each sample and analyzed for association with colonic site and disease state using a suite of bioinformatic approaches. Localization of select proteins was determined by immunoblot analysis and immunohistochemistry of human endoscopic biopsy samples. RESULTS: Co-occurrence analysis of the discovery cohort metaproteome showed that proteins at the mucosal surface clustered into modules with evidence of differential functional specialization (eg, iron regulation, microbial defense) and cellular origin (eg, epithelial or hemopoietic). These modules, validated in an independent cohort, were differentially associated spatially along the gastrointestinal tract, and 7 modules were associated selectively with non-IBD, ulcerative colitis, and/or Crohn's disease states. In addition, the detailed composition of certain modules was altered in disease vs healthy states. We confirmed the predicted spatial and disease-associated localization of 28 proteins representing 4 different disease-related modules by immunoblot and immunohistochemistry visualization, with evidence for their distribution as millimeter-scale microgeographic mosaic. CONCLUSIONS: These findings suggest that the mucosal surface is a microgeographic mosaic of functional networks reflecting the local mucosal ecology, whose compositional differences in disease and healthy samples may provide a unique readout of physiologic and pathologic mucosal states.

Banal no more: an essay on the film Hannah Arendt, with special reference to Eichmann and the Nazi killing groups.

This movie review and essay about the recent film Hannah Arendt by director Margarethe von Trotta seeks to examine Arendt's controversial term "banality of evil" as well as the nature of Arendt's misperception of Adolph Eichmann as thoughtless, and to situate Eichmann's personality within recent understandings of totalitarian group behavior and organizational killers. What emerges is that Arendt was unable to understand Eichmann's ruthless indifference to others as well as his attraction to being a Nazi and to organized mass killing. This paper examines Mann's (2005) formulation of different levels of functional attraction to totalitarian perpetrators, in which a racial morality is imposed and restrictions to eliminist violence are removed. Under such group conditions, violent "sleeper" needs emerge and are rationalized by political beliefs. In conclusion, the term "banality of evil" has little explanative value, while violent mass murder continues to this day as a totalitarian solution.

Mutual attention and joint gaze as developmental forerunners of the therapeutic alliance.

This paper attempts to integrate child developmental research and early childhood neural-cognitive development within the complexities of the early infant-mother relationship as described by psychoanalytic theory. Accumulating research evidence for the importance of the complex transition from mutual gaze to joint gaze calls into question the origin and analytic significance of the alliance relationship that emerges from the primary relationship between the mother and child. This paper explores the apparently neglected relationship between the respective theories of the therapeutic alliance of Zetzel, Greenson, and Brenner, and the developmental progression from mutual gaze and joint gaze, upon which important aspects of mental and cognitive development rest. Nonblind infants and children rely heavily on the ability to see in order to learn and form representations, while trauma affects these dynamics and perception. This issue is particularly relevant given the high incidence of unresolved childhood trauma in the form of neglect, loss, and abuse in those who seek out therapy. Freud's original conception of developmental phase progression has been unsubstantiated by recent researchers in terms of chronological progression and the receptors through which the infants experience the world. In this paper the author applies specific developmental lenses to this basic conception of the dyadic relationship in psychoanalytic treatment, and will reexamine and redefine both working and therapeutic alliance in the frame of an essential developmental stage of joint visual attention. A clinical example will reveal compromised normal preverbal interactive development, exposing faults in the complex transition from mutual gaze to joint gaze.

A nationwide 2010-2012 analysis of U.S. health care utilization in inflammatory bowel diseases.

BACKGROUND: Implementation of the 2010 Affordable Care Act (ACA) calls for a collaborative effort to transform the U.S. health care system toward patient-centered and value-based care. To identify how specialty care can be improved, we mapped current U.S. health care utilization in patients with inflammatory bowel diseases (IBD) using a national insurance claims database. METHODS: We performed a cross-sectional study analyzing U.S. health care utilization in 964,633 patients with IBD between 2010 and 2012 using insurance claims data, including pharmacy and medical claims. Frequency of IBD-related care utilization (medication, tests, and treatments) and their charges were evaluated. Subsequently, outcomes were put into the framework of current U.S. guidelines to identify areas of improvement. RESULTS: A disproportionate usage of aminosalicylates in Crohn's disease (42%), frequent corticosteroid use (46%, with 9% long-term users), and low rates of corticosteroid-sparing drugs (thiopurines 15%; methotrexate 2.7%) were observed. Markers for inflammatory activity, such as C-reactive protein or fecal calprotectin were not commonly used (8.8% and 0.13%, respectively). Although infrequently used (11%), anti-TNF antibody therapy represents a major part of observed IBD charges. CONCLUSIONS: This analysis shows 2010-2012 utilization and medication patterns of IBD health care in the United States and suggests that improvement can be obtained through enhanced guidelines adherence.

A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease.

Abnormalities of the intestinal microbiota are implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), two spectra of inflammatory bowel disease (IBD). However, the high complexity and low inter-individual overlap of intestinal microbial composition are formidable barriers to identifying microbial taxa representing this dysbiosis. These difficulties might be overcome by an ecologic analytic strategy to identify modules of interacting bacteria (rather than individual bacteria) as quantitative reproducible features of microbial composition in normal and IBD mucosa. We sequenced 16S ribosomal RNA genes from 179 endoscopic lavage samples from different intestinal regions in 64 subjects (32 controls, 16 CD and 16 UC patients in clinical remission). CD and UC patients showed a reduction in phylogenetic diversity and shifts in microbial composition, comparable to previous studies using conventional mucosal biopsies. Analysis of weighted co-occurrence network revealed 5 microbial modules. These modules were unprecedented, as they were detectable in all individuals, and their composition and abundance was recapitulated in an independent, biopsy-based mucosal dataset 2 modules were associated with healthy, CD, or UC disease states. Imputed metagenome analysis indicated that these modules displayed distinct metabolic functionality, specifically the enrichment of oxidative response and glycan metabolism pathways relevant to host-pathogen interaction in the disease-associated modules. The highly preserved microbial modules accurately classified IBD status of individual patients during disease quiescence, suggesting that microbial dysbiosis in IBD may be an underlying disorder independent of disease activity. Microbial modules thus provide an integrative view of microbial ecology relevant to IBD.

Bion, basic assumptions, and violence: a corrective reappraisal.

Group psychoanalytic theory rests on many of the same psychoanalytic assumptions as individual psychoanalytic theory but has been slow in developing its own language and unique understanding of conflict within the group, as many group phenomena are not the same as individual psychic events. Regressive fantasies and alliances within and to the group are determined by group composition and the interaction of fantasies among members and leader. Bion's useful but incomplete early abstract formulation of psychic regression in groups was the initial attempt to move beyond Freud's largely sociological view. This paper explores some of the origins of Bion's neglect of murderous violence in groups as a result of his own experiences in the first European war. In the following, I present evidence for the existence of a violent basic assumption and offer evidence as to Bion's avoidance of murderous and violent acts.

Host-microbe relationships in inflammatory bowel disease detected by bacterial and metaproteomic analysis of the mucosal-luminal interface.

BACKGROUND: Host-microbe interactions at the intestinal mucosal-luminal interface (MLI) are critical factors in the biology of inflammatory bowel disease (IBD). METHODS: To address this issue, we performed a series of investigations integrating analysis of the bacteria and metaproteome at the MLI of Crohn's disease, ulcerative colitis, and healthy human subjects. After quantifying these variables in mucosal specimens from a first sample set, we searched for bacteria exhibiting strong correlations with host proteins. This assessment identified a small subset of bacterial phylotypes possessing this host interaction property. Using a second and independent sample set, we tested the association of disease state with levels of these 14 "host interaction" bacterial phylotypes. RESULTS: A high frequency of these bacteria (35%) significantly differentiated human subjects by disease type. Analysis of the MLI metaproteomes also yielded disease classification with exceptional confidence levels. Examination of the relationships between the bacteria and proteins, using regularized canonical correlation analysis (RCCA), sorted most subjects by disease type, supporting the concept that host-microbe interactions are involved in the biology underlying IBD. Moreover, this correlation analysis identified bacteria and proteins that were undetected by standard means-based methods such as analysis of variance, and identified associations of specific bacterial phylotypes with particular protein features of the innate immune response, some of which have been documented in model systems. CONCLUSIONS: These findings suggest that computational mining of mucosa-associated bacteria for host interaction provides an unsupervised strategy to uncover networks of bacterial taxa and host processes relevant to normal and disease states. (Inflamm Bowel Dis 2012;).

A metaproteomic approach to study human-microbial ecosystems at the mucosal luminal interface.

Aberrant interactions between the host and the intestinal bacteria are thought to contribute to the pathogenesis of many digestive diseases. However, studying the complex ecosystem at the human mucosal-luminal interface (MLI) is challenging and requires an integrative systems biology approach. Therefore, we developed a novel method integrating lavage sampling of the human mucosal surface, high-throughput proteomics, and a unique suite of bioinformatic and statistical analyses. Shotgun proteomic analysis of secreted proteins recovered from the MLI confirmed the presence of both human and bacterial components. To profile the MLI metaproteome, we collected 205 mucosal lavage samples from 38 healthy subjects, and subjected them to high-throughput proteomics. The spectral data were subjected to a rigorous data processing pipeline to optimize suitability for quantitation and analysis, and then were evaluated using a set of biostatistical tools. Compared to the mucosal transcriptome, the MLI metaproteome was enriched for extracellular proteins involved in response to stimulus and immune system processes. Analysis of the metaproteome revealed significant individual-related as well as anatomic region-related (biogeographic) features. Quantitative shotgun proteomics established the identity and confirmed the biogeographic association of 49 proteins (including 3 functional protein networks) demarcating the proximal and distal colon. This robust and integrated proteomic approach is thus effective for identifying functional features of the human mucosal ecosystem, and a fresh understanding of the basic biology and disease processes at the MLI.

Local thrombolysis: a newer approach to treating inflammatory bowel disease-related thromboembolism.

GOALS: To review the experience with a relatively novel treatment, local thrombolysis, in patients with inflammatory bowel disease (IBD)-related thromboembolism (TE). BACKGROUND: TE is an extraintestinal complication of IBD for which there are no clear treatment guidelines. Systemic treatment with anticoagulants or thrombolytics often raises fear of hemorrhagic complications, particularly hematochezia. STUDY: Cases of IBD-related and non-IBD-related TE treated with local thrombolysis were searched for in PubMed, reviewed, and grouped into anatomic areas. Outcomes in each anatomic area were compared between IBD and non-IBD patients. Due to the small number of IBD-related TE cases, a descriptive, not statistical, analysis was performed. RESULTS: There were 17 cases of IBD-related TE treated with local thrombolysis grouped as follows: 7 of cerebral venous thrombosis, 3 of lower extremity arterial TE, 1 of deep vein thrombosis, 1 of upper extremity deep vein thrombosis, 3 of abdominal vein thrombosis, and 2 of inferior vena cava TE. Mean age was 32 (range, 14 to 50) years, and 13 of 17 patients were female. Twelve had ulcerative colitis, 3 had Crohn's disease, and 1 was indeterminate. Four of the 7 patients with active IBD had pretreatment hematochezia, 2 of whom had worsening of hematochezia secondary to treatment. The rates of radiologic resolution, clinical resolution, and hemorrhagic complications in the IBD patients were favorable in all the anatomic areas and were very similar to non-IBD patients. CONCLUSIONS: Local thrombolysis may be considered a viable therapeutic option for IBD-related TE. As more cases of local thrombolysis for IBD-related TE accumulate, further recommendations can be made as to the indications for its use.

Some problems with treatment: destructive enactments in combined therapy.

Abstract The aim and hope of combined therapy is that the arrangement of group and individual treatment affords greater therapeutic effect because of its psychic interactions. For some patients, the modalities together may lead to promising, if often complex, analysis through an open flow of information between the two modalities. However, the two cases I present illustrate problems that may arise in combined treatment. In these two cases, the interaction between the modalities may have prevented important working through and caused an irreparable breach in the therapeutic alliance. The interdependence among complex enactments, my countertransference, and the respective groups' transferences was emotionally complex. In this paper I describe various forms of these enactments, explore some ideas about why enactments occurred, and discuss their impact on the treatment of these patients.

Negativity and lies in analytic group therapy: an inquiry into Bion's ideas of K and -K.

In this paper a kind of therapeutic failure in psychoanalytic group work, one that is common but frequently overlooked, is described. Essentially this failure is the result of patients who mislead the therapist by lying and by a negative process of thought that works against analytic aims of acquiring understanding and emotional truth. These processes and their effects, as they are manifested by an individual patient in a group and by the therapist, are described. Bion's later theory of K and -K offers a framework for the discussion of the group events.

Costs and clinical outcomes of primary prophylaxis of variceal bleeding in patients with hepatic cirrhosis: a decision analytic model.

OBJECTIVE: Current guidelines recommend upper endoscopic screening for patients with hepatic cirrhosis and primary prophylaxis with a nonselective beta-blocker for those with large varices. METHODS: However, only 25% of cirrhotics develop large varices. Thus, the aim of this study is to evaluate the most cost-effective approach for primary prophylaxis of variceal hemorrhage. RESULTS: Using a Markov model, we compared the costs and clinical outcomes of three strategies for primary prophylaxis of variceal bleeding. In the first strategy, patients were given a beta-blocker without undergoing upper endoscopy. In the second strategy, patients underwent upper endoscopic screening; those found to have large varices were treated with a beta-blocker. In the third strategy, no prophylaxis was used. Selected sensitivity analyses were performed to validate outcomes. Our results show screening prophylaxis was associated with a cost of $37,300 and 5.72 quality-adjusted life yr (QALYs). Universal prophylaxis was associated with a cost of $34,100 and 6.65 QALYs. The no prophylaxis strategy was associated with a cost of $36,600 and 4.84 QALYs. The incremental cost-effectiveness ratio was $800/QALY for the endoscopic strategy relative to the no prophylaxis strategy. Screening endoscopy was cost saving when the compliance, bleed risk without beta-blocker, and variceal bleed costs were increased, and when the discount rate, bleed risk on beta-blockers, and cost of upper endoscopy were decreased. In contrast, the universal prophylaxis strategy was persistently cost saving relative to the no prophylaxis strategy. In comparing the strategies, sensitivity analysis on the death rates from variceal hemorrhage did not alter outcomes. CONCLUSIONS: Our results provide economic and clinical support for primary prophylaxis of esophageal variceal bleeding in patients with hepatic cirrhosis. Universal prophylaxis with beta-blocker is preferred because it is consistently associated with the lowest costs and highest QALYs.