Idiopathic CD4 Lymphocytopenia: Clinical and Immunologic Characteristics and Follow-Up of 40 Patients

Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria.We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19–70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed. Mean follow-up was 6.9 ± 6.7 (0.14–24.3) years. Infectious, autoimmune, and neoplastic events were recorded, as were outcomes of interleukin 2 therapy.In all, 25 patients had opportunistic infections (12 with human papillomavirus infection), 14 had autoimmune symptoms, 5 had malignancies, and 8 had mild or no symptoms. At the time of diagnosis, the mean cell counts were as follows: mean CD4 cell count: 127/mm³ (range, 4–294); mean CD8: 236/mm³ (range, 1–1293); mean CD19: 113/mm³ (range, 3–547); and mean NK cell count: 122/mm³ (range, 5–416). Most patients had deficiency in CD8, CD19, and/or NK cells. Cytotoxic function of NK cells was normal, and patients with infections had a significantly lower NK cell count than those without (p = 0.01). Patients with autoimmune manifestations had increased CD8 T-cell count. Proliferation of thymic precursors, as assessed by T-cell rearrangement excision circles, was increased. Six patients died (15%). CD4 T-cell count <150/mm³ and NK cell count <100/mm³ were predictors of death.In conclusion, ICL is a heterogeneous disorder often associated with deficiencies in CD8, CD19, and/or NK cells. Long-term prognosis may be related to initial CD4 and NK cell deficiency.Abbreviations: AIHA = autoimmune hemolytic anemia, CDC = Centers for Disease Control, CMV = cytomegalovirus, cpm = count per minute, CVID = common variable immunodeficiency, CXCR4 = C-X-C chemokine receptor type 4, HIV = human immunodeficiency virus, HLA = human leukocyte antigen, HPV = human papillomavirus, HTLV-1/2 = human T-cell lymphotropic 1/2, ICL = idiopathic CD4 T lymphocytopenia, IFN-γ = interferon-γ, IL = interleukin, JC virus = John Cunningham virus, LPA = lymphocyte proliferation assay, NK = natural killer, P = patient, PBMC = peripheral blood mononuclear cell, Pwd = pokeweed, SI = stimulation index, sj = signal joint, TREC = T-cell rearrangement excision circle     

Non-operative management of diverticular perforation in a patient with suspected Ehlers–Danlos syndrome

INTRODUCTION

No consensus exists regarding definitive management of colonic perforation in Ehlers–Danlos syndrome (EDS), with various authors advocating different operative techniques. Spontaneous colonic perforation is a recognised complication of vascular-type EDS (type IV), with many reported cases in the literature. No such cases have been reported concerning classical-type EDS (type I/II).

PRESENTATION OF CASE

A 55-year-old male with a family history of EDS presented with acute lower abdominal pain and signs of localised peritonitis. Following resuscitation, computerised tomography identified perforation of a sigmoid diverticulum with localised intraperitoneal air. Considering the potential complications associated with laparotomy in a patient with EDS, a trial of conservative management was undertaken including image-guided drainage of a mesenteric abscess. Intensive care monitoring, nutritional support and intravenous antibiotics also facilitated successful non-operative management. Following discharge, molecular studies confirmed COL5A1 mutation, and a diagnosis of classical Ehlers–Danlos syndrome was established.

DISCUSSION

This is the first reported case of successful conservative management of colonic diverticular perforation in a patient with classical Ehlers–Danlos syndrome.

CONCLUSION

EDS is highly significant in the surgical context, with the causative genetic factors serving to further complicate the course of surgical intervention. In the absence of consensus regarding best surgical management, due consideration should be given to non-operative management of benign colonic perforation.     

New evidence of ethanol's anxiolytic properties in the infant rat

Ethanol induces appetitive, aversive, and anxiolytic effects that are involved in the development of ethanol use and dependence. Because early ethanol exposure produces later increased responsiveness to ethanol, considerable effort has been devoted to analysis of ethanol's appetitive and aversive properties during early ontogeny. Yet, there is a relative scarcity of research related to the anxiolytic effects of ethanol during early infancy, perhaps explained by a lack of age-appropriate tests. The main aim of this study was to validate a model for the assessment of ethanol's anxiolytic effects in the infant rat (postnatal days 13–16). The potentially anxiolytic effects of ethanol tested included: i) amelioration of conditioned place aversion, ii) ethanol intake in the presence of an aversive conditioned stimulus, iii) the inhibitory behavioral effect in an anxiogenic environment, and iv) innate aversion to a brightly illuminated area in a modified light/dark paradigm. Ethanol doses employed across experiments were 0.0, 0.5, and 2.0 g/kg. Results indicated that a low ethanol dose (0.5 g/kg) was effective in attenuating expression of a conditioned aversion. Ethanol intake, however, was unaffected by simultaneous exposure to an aversive stimulus. An anxiogenic environment diminished ethanol-induced locomotor stimulation. Finally, animals given 0.5 g/kg ethanol and evaluated in a light/dark box showed increased time spent in the illuminated area and increased latency to escape from the brightly lit compartment than rats treated with a higher dose of ethanol or vehicle. These new results suggest that ethanol doses as low as 0.5 g/kg are effective in ameliorating an aversive and/or anxiogenic state in preweanling rats. These behavioral preparations can be used to assess ethanol's anxiolytic properties during early development.     

Smoothelin and caldesmon are reliable markers for distinguishing muscularis propria from desmoplasia: a critical distinction for accurate staging colorectal adenocarcinoma

An accurate distinction between deep muscularis propria invasion versus subserosal invasion by colonic adenocarcinoma is essential for the accurate staging of cancer and subsequent optimal patient management. However, problems may arise in pathologic staging when extensive desmoplasia blurs the junction between deep muscularis propria and subserosal fibroadipose tissue. To address this issue, forty-three (43) cases of colonic adenocarcinoma resections from 2007-2009 at The Methodist Hospital in Houston, TX were reviewed. These cases were selected to address possible challenges in differentiating deep muscularis propria invasion from superficial subserosal invasion based on H&E staining alone. Immunohistochemical staining using smooth muscle actin (SMA), smoothelin, and caldesmon were performed on 51 cases: 8 cases of pT1 tumors (used mainly as control); 12 pT2 tumors; and 31 pT3 tumors. All 51 (100%) had diffuse, strong (3+) immunoreactivity for caldesmon and smoothelin in the muscularis propria with a granular cytoplasmic staining pattern. However, the desmoplastic areas of these tumors, composed of spindled fibroblasts and myofibroblasts, showed negative immunostaining for caldesmon and smoothelin (0/35). SMA strongly stained the muscularis propria and weakly (1+) or moderately (2+) stained the spindled fibroblasts in the desmoplastic areas (the latter presumably because of myofibroblastic differentiation). Compared to SMA, caldesmon and smoothelin are more specific stains that allow better delineation of the muscularis propria from the desmoplastic stromal reaction which provides a critical aide for proper staging of colonic adenocarcinoma and subsequent patient care.     

Cell-based assays for the detection of MOG antibodies: a comparative study

Journal of Neurology - The detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) is fundamental for the identification of MOG antibody-associated disorders (MOGAD), and the...     

Spatial inhibition and the visual cortex: a magnetic resonance spectroscopy imaging study

Introduction

Deficits in processing spatial information have been observed in clinical populations who have abnormalities within the dopamine (DA) system. As psychostimulants such as methamphetamine (MA) are particularly neurotoxic to the dopaminergic system it was of interest to examine the performance of MA-dependent individuals on a task of spatial attention.

Method

51 MA-dependent subjects and 22 age-matched non-substance abusing control subjects were tested on a Spatial Stroop attention test. MR Spectroscopy (MRS) imaging data were analyzed from 32 MA abusers and 13 controls.

Results

No group differences in response time or accuracy emerged on the behavioral task with both groups exhibiting equivalent slowing when the word meaning and the spatial location of the word were in conflict. MRS imaging data from the MA abusers revealed a strong inverse correlation between NAA/Cr ratios in the Primary Visual Cortex (PVC) and spatial interference (p = 0.0001). Moderate inverse correlations were also seen in the Anterior Cingulate Cortex (ACC) (p = 0.02). No significant correlations were observed in the controls, perhaps due to the small sample of imaging data available (n = 13).

Discussion

The strong correlation between spatial conflict suppression and NAA/Cr levels within the PVC in the MA-dependent individuals suggests that preserved neuronal integrity within the PVC of stimulant abusers may modulate cognitive mechanisms that process implicit spatial information.     

Dental materials: 1979 literature review Part II

This paper, which is presented in two parts, reviews the work on dental materials published in 1979. Included in Part II are sections on impression materials, model, die and investment materials, waxes, acrylic resins, denture base polymers, soft lining materials and tissue conditioners, cast and wrought dental alloys, ceramics, implants and, finally, corrosion. Part I included sections on dental biomechanics, fissure sealants, cements, amalgam, composite filling materials, endodontic materials and microleakage.