Functional abnormalities of CD8+ T cells define a unique subset of patients with common variable immunodeficiency

A substantial subgroup of patients with common variable immunodeficiency (CVI) exhibit an abnormal T-cell phenotype characterized by a low CD4/CD8 ratio associated with a significant increase in the absolute number of CD8+ T cells (CVI4/8low patients). In the present study, we examined the phenotypic and functional properties of purified T-cell subsets in this group of CVI patients. CD8+ T cells from CVI4/8low patients manifested increased expression of HLA-DR and CD57 and decreased expression of CD45RA as compared with CD8+ T cells from normal controls. When stimulated with anti-CD3 and phorbol 12-myristate 13-acetate, purified patient CD8+ T cells exhibited significantly decreased proliferation, c-myc expression, and interleukin-2 (IL-2) production compared with that of normal CD8+ T cells. Nevertheless, mitogen-activated patient CD8+ T cells secreted elevated amounts of gamma-interferon and IL-5 and normal amounts of IL- 4. This abnormal pattern of proliferation and cytokine production was limited to the CD8+ T-cell subset as CD4+ T cells from these patients exhibited normal proliferation and cytokine production. In further functional studies, purified CD8+ T cells from CVI4/8low patients manifested increased cytotoxic T-lymphocyte activity and suppressor activity, as compared with normal CD8+ T cells, when they were tested in (1) an anti-CD3 "redirected" cytotoxicity assay and (2) a suppressor assay consisting of CD8+ T cells and Staphylococcus aureus Cowan I (SAC) plus IL-2-stimulated normal (allogeneic) B cells. In the latter case, patient CD8+ T cells suppressed IgG production, but not IgM production. Finally, in studies to evaluate the role of patient CD8+ T cells in the pathogenesis of hypogammaglobulinemia, we determined the capacity of SAC and IL-2 to induce Ig production in highly purified patient B cells, ie, in the absence of patient CD8+ T cells. We found that, whereas B cells from one patient produced normal amounts of IgG, B cells from three patients were unable to produce normal amounts of IgG under these conditions. These data establish the phenotypic and functional characteristics of CD8+ T cells in CVI4/8low and clearly distinguish CVI4/8low patients from other patients with this syndrome. The data do not support the contention that hypogammaglobulinemia in CVI4/8low patients is due to a direct effect of CD8+ T cells on terminal B-cell differentiation, except in the occasional patient. The abnormal CD8+ T cells may, nevertheless, have more subtle effects of lymphoid function that play a role in disease pathogenesis.     

Exchange transfusion in the treatment of patients with acute hepatitis in coma

Summary Acute hepatic necrosis with profound coma carries an ominous prognosis. Conventional therapy has had little influence on recovery. Various new therapeutic modalities are currently being tried. Survival figures derived by compiling reports on exchange transfusion are somewhat encouraging when the data are compared to the salvage rate in patients with fulminant hepatitis treated conventionally, even after the addition of steroids. Current knowledge is lacking as to the specific lethal factor (s) and/or mechanism (s) that are operating in these patients. Pathogenetic ignorance notwithstanding, the remarkable regenerative power of the liver dictates that all efforts be made to sustain life, as the therapist hopefully awaits recovery. If facilities and personnel are available, we feel exchange transfusion should be considered when 24 hr of intensive conventional therapy, including high doses of steroids, fails to bring about significant improvement. Any decision on duration of therapy in the absence of neurologic improvement remains arbitrary. Histologic evidence of liver cell regeneration, if it can be obtained, may justify continued therapeutic efforts. Exchange transfusion must be evaluated by a cooperative controlled study before its therapeutic value can be established.     

Chronic triceps insufficiency managed with extensor carpi radialis longus and palmaris longus tendon grafts

Chronic triceps insufficiency, causing prolonged disability, occurs due to a missed diagnosis of an acute rupture. We report a 25 year old male with history of a significant fall sustaining multiple injuries. Since then, he had inability in extending his right elbow for which he sought intervention after a year. Diagnosis of triceps rupture was made clinicoradiologically and surgery was planned. Intraoperative findings revealed a deficient triceps with a fleck of avulsed bone from olecranon. Ipsilateral double tendon graft including extensor carpi radialis longus and palmaris longus were anchored to triceps and secured with the olecranon. Six-months follow revealed a complete active extension of elbow and a full function at the donor site.     

Evaluation of axillary lymphadenectomy without axillary drainage for patients undergoing breast-conserving therapy

Background: The routine use of drainage after axillary node dissection in patients undergoing breast-conserving therapy (BCT) is being questioned. To determine the value of routine drainage, we evaluated the postoperative course of patients with primary breast carcinoma who underwent axillary dissection with or without axillary drainage. Methods: A retrospective review of 69 patients prompted a prospective randomized trial of 46 patients undergoing BCT at our tertiary cancer center. Variables studied were age, treatment (drain or no drain), number and tumor status of excised lymph nodes, size of primary tumor, duration of drainage or aspiration, number and volume of aspirations, number of office visits, incidence of complications and degree of pain, change in arm or forearm circumference, and body mass index (BMI). Data from prospective and retrospective studies were pooled for analysis. Results: Of 115 patients, 72 were treated with a drain (Drain group) and 43 were not (No-drain group). Overall there was no difference in the number or tumor status of excised nodes, the size of the primary tumor, or the incidence of complications between the two groups. Aspiration was required in 50% of the No-drain patients and 8.3% of the Drain patients. The incidence of drain placement or replacement postoperatively was 9.3% for the No-drain patients and 4.2% for the Drain patients. The No-drain patients had more office visits (5.1±0.4 vs. 3.6±0.1;P=.0002) and a longer interval between operation and last aspiration or drain removal (16.2±1.4 days vs. 11.3±0.6 days;P=.0040). Findings were similar in the subgroup of 46 prospectively studied patients, who included 24 Drain patients and 22 No-drain patients. In this group, pain evaluation using a scale of 0 to 10 showed a mean rating of 4.2±2.6 in Drain patients and 2.7±0.4 in No-drain patients (P=.0062). Conclusions: Axillary node dissection can be managed with or without a drain. More office visits but less pain can be expected if a drain is not used.Presented at the 50th Annual Cancer Symposium of The Society of Surgical Oncology, Chicago, IL, March 20–23, 1997.The views expressed herein are those of the authors and do not necessarily reflect the views of the United States Army, United States Navy, Uniformed Services University of the Health Sciences, or the Department of Defense.     

Splanchnic artery aneurysms and pseudoaneurysms: transcatheter embolization

Over the past 7 years, eight patients with splanchnic artery aneurysms and pseudoaneurysms were studied and treated. Transcatheter embolization resulted in occlusion of the lesions in all eight patients. Potentially risky and difficult surgery was avoided completely in four patients. Three patients had elective surgery at a later date when their condition was more stable. The remaining patient had definitive surgery after embolization. Transcatheter embolization should be the initial treatment of choice in splanchnic artery aneurysms and pseudoaneurysms.     

Embryonic hematopoiesis in mice and humans

Aim : The aim of this report is to review briefly the ontogeny of hematopoiesis in mice and humans and to discuss recent evidence for an intraembryonic source of hematopoietic stem cells. Methods : The hematopoiesis overview summarizes information present in the PubMed online database and from experiments conducted in our laboratories. Results : The major sites of hematopoiesis change throughout development in mice and humans. Recent evidence suggests that hematopoietic cells may emerge from mesoderm precursors within the embryo as well as in the yolk sac.
Conclusion : The ontogeny of hematopoiesis is similar in mice and humans. The murine system is a useful model to study the earliest events involved in forming hematopoietic stem cells.