Kaposi's sarcoma with a non-Hodgkin's lymphoma. Its association in a male homosexual with human T-cell lymphotropic virus type III infection

Combined tumor syndromes, specifically reticuloendothelial malignancies and Kaposi’s sarcoma, have long been recognized. With the recognition of the acquired immunodeficiency syndrome (AIDS), several patients with concurrent non-Hodgkin’s lymphoma and Kaposi’s sarcoma have been reported at high risk for developing AIDS. The present Centers for Disease Control definition of AIDS excludes these patients on the assumption that one tumor is affecting the cellular immunity, allowing for the development of the second malignancy. In evaluating such a patient who had serologic evidence of human T-cell lymphotropic virus type III infection, the probable cause of AIDS, we have reviewed reports of patients with similar concurrent malignancies before and since the onset of the AIDS epidemic. We conclude that patients in high-risk groups for AIDS who develop similar combined tumor syndromes should be classified as having AIDS

Longitudinal dynamics of circulating tumor cells and circulating tumor DNA for treatment monitoring in metastatic breast cancer

PURPOSE: Liquid biopsy-based biomarkers, including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), are increasingly important for the characterization of metastatic breast cancer (MBC). The aim of the study was to explore CTCs and ctDNA dynamics to better understand their potentially complementary role in describing MBC. METHODS: The study retrospectively analyzed 107 patients with MBC characterized with paired CTCs and ctDNA assessments and a second prospective cohort, which enrolled 48 patients with MBC. CTCs were immunomagnetically isolated and ctDNA was quantified and then characterized through next-generation sequencing in the retrospective cohort and droplet digital polymerase chain reaction in the prospective cohort. Matched pairs variations at baseline, at evaluation one (EV1), and at progression were tested through the Wilcoxon test. The prognostic role of ctDNA parameters was also investigated. RESULTS: Mutant allele frequency (MAF) had a significant decrease between baseline and EV1 and a significant increase between EV1 and progression. Number of detected alterations steadily increased across timepoints, CTCs enumeration (nCTCs) significantly increased only between EV1 and progression. MAF dynamics across the main altered genes was then investigated. Plasma DNA yield did not vary across timepoints both in the retrospective cohort and in the prospective cohort, while the short fragments fraction showed a potential role as a prognostic biomarker. CONCLUSION: nCTCs and ctDNA provide complementary information about prognosis and treatment benefit. Although nCTCs appeared to assess tumor biology rather than tumor burden, MAF may be a promising biomarker for the dynamic assessment of treatment response and resistance

Up-regulation of NMDA receptor subunit and post-synaptic density protein expression in the thalamus of elderly patients with schizophrenia

Numerous studies have described structural and functional abnormalities of the thalamus in schizophrenia, but surprisingly few studies have examined neurochemical abnormalities that accompany these pathological changes. We previously identified abnormalities of multiple molecules associated with glutamatergic neurotransmission, including changes in NMDA receptor subunit transcripts and binding sites and NMDA receptor-associated post-synaptic density (PSD) protein transcripts in the thalamus of elderly patients with schizophrenia. In the present study, we performed western blot analysis to determine whether protein levels of NMDA receptor subunits (NR1, NR2A, NR2B) and associated PSD proteins (NF-L, PSD95, SAP102) are altered in schizophrenia. Thalamic tissue from each subject was grossly dissected into two regions: a dorsomedial region containing limbic-associated dorsomedial, anterior and central medial thalamic nuclei; and a ventral thalamus region that primarily consisted of the ventral lateral nucleus. We observed increased protein expression of the NR2B NMDA receptor subunit and its associated intracellular protein, PSD95, in the dorsomedial thalamus of patients with schizophrenia, but the other molecules were unchanged, and we found no changes in the ventral thalamus. These data provide additional evidence of thalamic neurochemical abnormalities, particularly in thalamic nuclei which project to limbic regions of the brain. Further, these findings provide additional evidence of NMDA receptor alterations in schizophrenia, which may play an important role in the neurobiology of the illness.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65970/1/j.1471-4159.2006.03954.x.pd

A four-dimensional probabilistic atlas of the human brain

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype-phenotype-behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

Postsplenectomy infections

Serious postsplenectomy infection is a significant threat to patients. Although the incidence of such infection is low, the resultant mortality is extremely high. This susceptibility to infection and ensuing mortality results from multiple immunologic changes that occur after splenectomy. These changes include alteration in immunoglobulin levels, loss of serum opsonizing proteins, and alterations in antigen clearance and cellular immunity

Amygdala volume in schizophrenia: post-mortem study and review of magnetic resonance imaging findings.

BACKGROUND: Claims that schizophrenia is a disease of the limbic system have been strengthened by meta-analyses of magnetic resonance imaging (MRI) studies finding reduced hippocampus and amygdala volumes. Some post-mortem studies do not find these abnormalities. AIMS: To assess the volume of the amygdala in a series of brains post-mortem. METHOD: Amygdala volume was estimated using point-counting in both hemispheres of the brains of 10 male and 8 female patients with schizophrenia, and a comparison group of 9 males and 9 females. RESULTS: No significant reduction of amygdala volume was found. CONCLUSIONS: Significant volume reduction of the amygdala is not a consistent feature of schizophrenia; findings from early MRI studies using coarse delineation methods may introduce bias to subsequent meta-analyses