Production of lymphotoxin and tumor necrosis factor by human neonatal mononuclear cells

Lymphotoxin (LT) and tumor necrosis factor (TNF) are cytokines with many common biologic effects including antiviral activity and induction of fever and the acute phase response; despite common effects, they are molecularly distinct. Because neonates are unduly susceptible to viral infection and frequently fail to mount a febrile response to infection, we hypothesized that neonatal cells would produce less LT and TNF than adult cells. We analyzed LT and TNF production by blood mononuclear cells and purified T cells using Northern blot analysis to detect specific messenger ribonucleic acid and specific assays to detect LT and TNF protein in culture supernatants. Compared to LT, TNF messenger ribonucleic acid and protein were produced more rapidly both by total mononuclear cells and by T cells in response to mitogen stimulation. Although there was intersubject variability, adult and neonatal mononuclear cells and T cells (n = 6) produced similar amounts of LT and TNF messenger ribonucleic acid and protein with similar kinetics. In experiments with phytohemagglutinin-stimulated mononuclear cells from ten additional subjects, supernatant LT was somewhat greater in neonatal cultures (neonatal = 62.8 +/- 60.5, adult = 13.2 +/- 10.7 units/ml, p less than 0.05), and TNF was somewhat greater in adult cultures (neonatal = 708 +/- 429, adult = 1987 +/- 392 pg/ml, p less than 0.01) at 24 h; results at 48 h and 72 h were similar. Thus, neonatal MC produced as much or more LT than did adult MC. Although the decreased production of TNF by neonatal MC was statistically significant, these cells did produce substantial amounts of this cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maternal transmission of acquired immune deficiency syndrome

Acquired immune deficiency syndrome (AIDS) has been reported in previously healthy homosexual or bisexual males, intravenous drug users, heterosexual men with hemophilia, and Haitians. The finding of heterosexual hemophiliacs with AIDS has raised the possibility of a transmittable blood-borne agent as a cause of this disease. We have found three female half-siblings who had clinical and laboratory evidence for AIDS. All three had evidence of abnormal in vitro cellular immunity; two had chronic active Epstein-Barr virus infection and lymphadenopathy; all three had chronic cutaneous Candida sp infection; and two had Pneumocystis carinii pneumonia. Their mother is a prostitute/drug addict with abnormal T-cell immunity including clinical and laboratory findings of mucocutaneous candidiasis. Histocompatibility typing is consistent with the history of different fathers for each child. Immunologic studies in one child evaluated prospectively from birth were abnormal by 2 months of age. These findings and the clinical histories indicate AIDS and strongly suggest vertical transmission of an agent(s) during the perinatal period.     

Significance of a positive antinuclear antibody test in a pediatric population

Clinical and laboratory findings in 138 children seen during a ten-year period with a positive antinuclear antibody (ANA) test were reviewed. Two thirds (91 of 138) of the patients had specific autoimmune or rheumatic diseases, including systemic lupus erythematosus (n = 37), juvenile rheumatoid arthritis (n = 33), Sj?gren's syndrome (n = 9), mixed connective tissue disease (n = 7), dermatomyositis (n = 3), and discoid lupus (n = 2). Another 27 patients had symptoms of autoimmune disease but did not fit criteria for specific disorders. Nine patients with IgA deficiency had a positive ANA test but did not have symptomatic autoimmune disease. Ten children had a positive ANA test in association with infections, mainly viral, and one had leukemia. Because most children with a positive ANA test had readily diagnosable autoimmune disorders, pediatric patients with a positive ANA on repeated testing should undergo clinical and laboratory studies for autoimmune or rheumatic disease.     

Characteristics of patients with abnormal stress technetium Tc 99m sestamibi SPECT studies without significant coronary artery diameter stenoses

BACKGROUND: Single-photon emission computed tomography (SPECT) sestamibi (MIBI) is an excellent tool for detection of coronary artery disease (CAD), preoperative risk assessment, and follow-up management after coronary revascularization. While the sensitivity of MIBI SPECT for detecting CAD has been reported to exceed 90%, the specificity ranges between 53-100%. HYPOTHESIS: The study was undertaken to assess characteristics of patients with abnormal stress technetium Tc99m sestamibi SPECT (MIBI) studies without significant coronary artery diameter stenoses (< 50%). METHODS: Between January 1999 and November 2000, 270 consecutive patients were referred for coronary angiography due to reversible MIBI uptake defects during exercise. In 41 patients (15%; 39% women, mean age 59 +/- 9 years), reversible MIBI uptake defects were assessed although coronary angiography showed no significant CAD. These patients were compared with age- and gender-matched patients with perfusion abnormalities (39% women, mean age 60 +/- 9 years), due to significant CAD (coronary artery stenosis > 50%). RESULTS: There were no significant differences between the two groups regarding body mass index, left bundle-branch block (LBBB), or method of stress test (dipyridamole in patients with LBBB or physical inactivity [n = 11] and exercise in all the others [n = 30]). Left ventricular hypertrophy (44 vs. 23%, p = 0.05) and left anterior fascicular block (LAFB) (17 vs. 0%, p = 0.005) were more common in patients with perfusion abnormalities with no significant CAD, whereas ST-segment depression during exercise (17 vs. 37% p = 0.05) and angina during exercise (15 vs. 29%, p = 0.02) were significantly less common than in patients with abnormal MIBI perfusion studies and angiographically significant CAD. Sestamibi uptake defects during exercise were significantly smaller in patients without significant CAD than in matched controls with significant CAD (p < 0.0004). CONCLUSION: Of 270 consecutive patients, 41 (15%) referred to coronary angiography due to reversible MIBI uptake defects showed coronary artery stenoses < 50%. Twenty-six (10%) of these presented angiographically normal coronary arteries. The significantly higher proportion of left ventricular hypertrophy and LAFB in patients with reversible MIBI uptake defects without significant CAD suggest microvascular disease, angiographically underestimated CAD, and conduction abnormalities as underlying mechanisms.     

Morbidity of breast cancer patients following complete axillary dissection or sentinel node biopsy only: a comparative evaluation

Introduction The usefulness of routine axillary dissection (AD) at levels I–II in breast cancer patients has been questioned for years because of the high postoperative morbidity in the shoulder and arm region, and the increasing number of patients with negative nodes. Sentinel node biopsy (SNB) was hoped both to reduce morbidity and to improve the reliability of staging. This study was designed to provide more evidence in this matter by comparing the follow-up data of patients with AD and those with SNB only. Method One hundred forty patients who had undergone AD between 1993 and 1996 were questioned for their subjective and objective symptoms using a questionnaire and subsequently subjected to a clinical examination. Their data were compared with those of 57 patients who had undergone SNB only between 1998 and 2000. Results Local recurrences have not been seen to date. The difference between the two groups in terms of a loss of quality of life was negligible. The differences in overall complaints, number of symptoms, pain, limited range of motion of the operated upper extremity, numbness, paresthesias, and arm swelling as well as perceived disability in activities of daily living were significantly in favor of SNB. The length of hospital stay was significantly shorter for SNB patients. Conclusion SNB appears to be an accurate procedure for axillary nodal staging in breast cancer patients and is associated with reduced postoperative morbidity and length of hospital stay. But it is still investigational and should not be implemented as therapeutical standard before results of randomized trials are published.