The preleukemic syndrome (hematopoietic dysplasia)

It has been recognized for many decades that epithelial dysplasia can represent an early histological sign of epithelial neoplasia. So it is with hematopoietic tissue wherein dysplasia of bone marrow cells can be an early sign of impending acute myeloid leukemia. Although this 'preleukemic syndrome' of hematopoietic dysplasia can often be identified well in advance of the classic histological signs of acute leukemia, a wide variety of basic studies on bone marrow cells, from patients and from experimental animals with induced preleukemia, clearly indicate that the preleukemic marrow cells are members of a fully established neoplastic clone. Consequently, it is likely that the preleukemic syndrome is merely acute leukemia diagnosed earlier than usual and which, in some patients, can be very slowly progressive, and in others may not progress at all. This article reviews the evidence in support of the notion that the preleukemic syndrome is an 'early leukemia', places the preleukemic syndrome in the context of a larger group of myelodysplastic disorders, reviews the laboratory studies of value for both diagnosis and for use in the assessment of prognosis, and summarizes the therapeutic options available for the management of patients with this disorder.     

Faking specific disorders: a study of the Structured Interview of Reported Symptoms (SIRS).

An untested assumption of malingering research is that persons who feign mental illness will not attempt to fake a particular disorder, but will be content to fabricate non-specific and possibly global psychiatric impairment. We tested the effectiveness of the Structured Interview of Reported Symptoms (SIRS) to detect feigning of three diagnostic groupings: schizophrenia, mood disorders, and PTSD on 45 psychologically knowledgeable correctional residents. We found that the SIRS maintained its powers of discrimination with respect to clinical samples. Similar research on faking specific disorders is needed on the MMPI-2 and other psychological measures.     

Relationship between conjugate lateral eye movements and alexithymia.

The relationship between conjugate lateral eye movements (CLEMs) and alexithymia was investigated in a group of 60 (23 male and 37 female) right-handed university students. Subjects completed the Toronto Alexithymia Scale (TAS), the Schalling-Sifneos Personality Scale, and the Basic Personality Inventory, which measures 12 basic dimensions of personality and psychopathology, CLEMs were recorded while subjects were asked 20 general knowledge questions that have no tendency to elicit eye movements predominantly in one direction. A series of gender by CLEM preference (left vs. right mover) ANOVAs were conducted with the various measures. There was a significant relationship between right CLEM preference and higher scores on the TAS, but no relationships between CLEMs and any of the other measures. These results suggest that alexithymia is associated with left cerebral lateralization, and support the hypothesis that alexithymic characteristics reflect a variation in brain organization.     

Problems with measuring alexithymia

Research evaluating the relationship of alexithymia to medical and psychiatric disorders has been compromised by the poor psychometric properties of the instruments that have been used to measure alexithymia. This study evaluated the psychometric properties of a recently introduced measure of alexithymia--the revised Schalling-Sifneos Personality Scale (SSPS-R). While the factor structure of the SSPS-R was found to be reasonably congruent with the theoretical domains of the alexithymia construct, the scale lacked homogeneity and internal reliability. These results are compared with the reliability and validity of other available measures of alexithymia. Recommendations are offered for the improved assessment of alexithymia in future research studies.     

The Revised Toronto Alexithymia Scale: some reliability, validity, and normative data.

Addressing certain problems with the compositional structure of the self-report Toronto Alexithymia Scale, this paper reports the development of a revised version of the scale as well as results from a preliminary series of studies evaluating its reliability and validity. The Revised Toronto Alexithymia Scale (TAS-R) demonstrated good internal consistency and a stable and replicable two-factor structure that is congruent with the two major dimensions of the alexithymia construct. Evidence of convergent and discriminant validity for the TAS-R was provided by correlations with measures of other constructs. Criterion validity was demonstrated by the ability of TAS-R scores to discriminate between behavioral medicine outpatients designated alexithymic and those designated non-alexithymic on the basis of clinical interview ratings. Normative data are provided for university student, normal adult, and psychiatric outpatient populations.     

Alexithymia and Pathological Gambling

ABSTRACT

The purpose of this study was to study the relationship between alexithymia and gambling in a community sample of pathological gamblers. Pathological, problem and non-problem gamblers were recruited from the community via advertisements and completed an assessment of their gambling behavior and the Toronto Alexithymia Scale. Alexithymia was higher among male pathological gamblers who identified slot machines, cards, and lotteries as their primary gambling problem. High alexithymics scored higher on Diagnostic and Statistical Manual symptoms related to poor self-regulation, communication, and problem-solving skills. Although a correlational study, the evidence suggests that further investigation of the clinical significance of alexithymia in individuals with severe gambling pathology is indicated.     

Graft-versus-host disease after liver transplantation is associated with bone marrow failure,hemophagocytosis, and DNMT3A mutations

Graft-versus-host disease after liver transplantation (LT-GVHD) is rare, frequently fatal, and associated with bone marrow failure (BMF), cytopenias, and hyperferritinemia. Given hyperferritinemia and cytopenias are present in hemophagocytic lymphohistiocytosis (HLH), and somatic mutations in hematopoietic cells are associated with hyperinflammatory responses (clonal hematopoiesis of indeterminate potential, CHIP), we identified the frequency of hemophagocytosis and CHIP mutations in LT-GVHD. We reviewed bone marrow aspirates and biopsies, quantified blood/marrow chimerism, and performed next-generation sequencing (NGS) with a targeted panel of genes relevant to myeloid malignancies, CHIP, and BMF. In all, 12 marrows were reviewed from 9 LT-GVHD patients. In all, 10 aspirates were evaluable for hemophagocytosis; 7 had adequate DNA for NGS. NGS was also performed on marrow from an LT cohort (n = 6) without GVHD. Nine of 10 aspirates in LT-GVHD patients showed increased hemophagocytosis. Five (71%) of 7 with LT-GVHD had DNMT3A mutations; only 1 of 6 in the non-GVHD LT cohort demonstrated DNMT3A mutation (p = .04). Only 1 LT-GVHD patient survived. BMF with HLH features was associated with poor hematopoietic recovery, and DNMT3A mutations were over-represented, in LT-GVHD patients. Identification of HLH features may guide prognosis and therapeutics. Further studies are needed to clarify the origin and impact of CHIP mutations on the hyperinflammatory state.

     

A monokine regulates colony-stimulating activity production by vascular endothelial cells

Human umbilical vein endothelial cells were cultured in supernatants of peripheral blood monocytes that had been cultured for 3 days with and without lactoferrin. Colony-stimulating activity (CSA) was measured in supernatants of the endothelial cell cultures and appropriate control cultures using normal, T-lymphocyte-depleted, phagocyte-depleted, low- density bone marrow cells in colony growth (CFU-GM) assays. Monocyte- conditioned medium contained a nondialyzable, heat labile factor that enhanced 4-15--fold the production of CSA by endothelial cells. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 69%. Lactoferrin did not inhibit CSA production by monokine-stimulated endothelial cells. Therefore, vascular endothelial cells are potent sources of CSA, the production of CSA by these cells is regulated by a stimulatory monokine, and the production and/or release of the monokine is inhibited by lactoferrin, a neutrophil- derived putative feedback inhibitor of granulopoiesis. Inasmuch as a similar monokine is known to stimulate CSA production by fibroblasts and T lymphocytes, we suggest that mononuclear phagocytes play a pivotal role in the regulation of granulopoiesis by recruiting a variety of cell types to produce CSA.