The role of eosinophils and neutrophils in helminth-induced keratitis

PURPOSE: Intrastromal injection of mice with antigens from the parasitic helminth that causes river blindness (Onchocerca volvulus) induces eosinophil recruitment to the corneal stroma at the time of maximum corneal opacification and neovascularization. The present study was conducted to examine the role of eosinophils and neutrophils in onchocercal keratitis in control C57Bl/6 mice and in interleukin-5 gene knockout (IL-5(-/-)) mice. METHODS: C57Bl/6 and IL-5(-/-) mice were immunized subcutaneously and injected intrastromally with soluble O. volvulus antigens. Mice were killed at various times thereafter. Development of keratitis was assessed by slit lamp examination, and inflammatory cells in the cornea were identified by immunohistochemistry. RESULTS: A biphasic recruitment of inflammatory cells was observed in C57Bl/6 mice; neutrophils predominated during the first 72 hours after intrastromal injection and subsequently declined, whereas eosinophil recruitment increased as time elapsed and comprised the majority (90%) of cells in the cornea by day 7. In contrast, neutrophils were the predominant inflammatory cells in IL-5(-/-) mice at early and late time points and were associated with extensive stromal damage and corneal opacification and neovascularization. Eosinophils were not detected in these mice at any time. CONCLUSIONS: In the absence of eosinophils, neutrophils can mediate keratitis induced by helminth antigens. Together with the early neutrophilic infiltrate in control animals, these observations indicate that neutrophils have an important role in onchocercal keratitis.     

The importance of the lumpectomy surgical margin status in long-term results of breast conservation

BACKGROUND: The impact of the surgical margin status on long-term local control rates for breast cancer in women treated with lumpectomy and radiation therapy is unclear. METHODS: The records of 289 women with 303 invasive breast cancers who were treated with lumpectomy and radiation therapy from 1972 to 1992 were reviewed. The surgical margin was classified as positive (transecting the inked margin), close (less than or equal to 2 mm from the margin), negative, or indeterminate, based on the initial biopsy findings and reexcision specimens, as appropriate. Various clinical and pathologic factors were analyzed as potential prognostic factors for local recurrence in addition to the margin status, including T classification, N classification, age, histologic features, and use of adjuvant therapy. The mean follow-up was 6.25 years. RESULTS: The actuarial probability of freedom from local recurrence for the entire group of patients at 5 and 10 years was 94% and 87%, respectively. The actuarial probability of local control at 10 years was 98% for those patients with negative surgical margins versus 82% for all others (P = 0.007). The local control rate at 10 years was 97% for patients who underwent reexcision and 84% for those who did not. Reexcision appears to convey a local control benefit for those patients with close, indeterminate, or positive initial margins, when negative final margins are attained (P = 0.0001). Final margin status was the most significant determinant of local recurrence rates in univariate analysis. By multivariate analysis, the final margin status and use of adjuvant chemotherapy were significant prognostic factors. CONCLUSIONS: The attainment of negative surgical margins, initially or at the time of reexcision, is the most significant predictor of local control after breast-conserving treatment with lumpectomy and radiation therapy.     

Identification of a receptor mediating absorption of dietary cholesterol in the intestine

Here we show that scavenger receptor class B type I is present in the small-intestine brush border membrane where it facilitates the uptake of dietary cholesterol from either bile salt micelles or phospholipid vesicles. This receptor can also function as a port for several additional classes of lipids, including cholesteryl esters, triacylglycerols, and phospholipids. It is the first receptor demonstrated to be involved in the absorption of dietary lipids in the intestine. In liver and steroidogenic tissues, the physiological ligand of this receptor is high-density lipoprotein. We show that binding of high-density lipoprotein and apolipoprotein A-I to the brush border membrane-resident receptor inhibits uptake of cholesterol (sterol) into the brush border membrane from lipid donor particles. This finding lends further support to the conclusion that scavenger receptor BI catalyzes intestinal cholesterol uptake. Our findings suggest new therapeutic approaches for limiting the absorption of dietary cholesterol and reducing hypercholesterolemia and the risk of atherosclerosis.     

Lower levels of physical functioning are associated with higher body weight among middle-aged and older women

OBJECTIVE: To compare levels of physical function, across levels of body mass index (BMI), among middle- to older-aged women. DESIGN: Cross-sectional study. Physical function, body weight and other covariates were measured in 1992. SUBJECTS: 56510 women aged 45-71 y, free of cardiovascular disease and cancer, participating in the Nurses' Health Study. MAIN OUTCOME MEASURES: The four physical function scores on the Medical Outcomes Study (MOS) Short Form-36 (SF36) Health Survey: physical functioning, vitality, bodily pain and role limitations. RESULTS: After adjusting for age, race, smoking status, menopausal status, physical activity and alcohol consumption, there was a significant dose-response gradient between increasing levels of BMI in 1992 and reduced function. For example, women with a BMI between 30-34.9 kg/m2 averaged: 9.0 point lower physical functioning score (95% Confidence interval (CI) -9.5, -8.5), 5.6 point lower vitality score (95% CI: -6.1, -5.1), and 7.0 point lower freedom from pain score (95% CI: -7.6, -6.4). These declines represent an approximate 10% loss of function compared to the reference category of women with BMIs ranging from 22.0-23.9 kg/m2. For the same BMI comparison, heavier women were at 66% increased risk of limitations in ability to work or perform other roles (RR = 1.66; 95% odds ratio (OR) CI: 1.56, 1.76). These findings were replicated when the sample was restricted to women who had maintained their BMI over a ten year period. CONCLUSIONS: In addition to increasing risk of chronic health conditions, greater adiposity is associated with lower every day physical functioning, such as climbing stairs or other moderate activities, as well as lower feelings of well-being and greater burden of pain.     

Evaluation criteria in follow-up studies of flexor tendon therapy

Oxphenisatin is known to induce liver damage and is suspected to cause or perpetuate chronic liver disease. In order to evaluate the hepatotoxic effect of long-term therapy with oxyphenisatin 26 consecutive patients with rheumatoid arthritis were investigated for the presence of liver disease. In all cases, liver biopsy, biochemical liver function tests and determination of Hepatitis-B antigen were performed. Ten patients showed no pathological changes in the liver biopsy and a further 2 had only non-specific changes. Seven patients had fatty liver, 5 passive congestion, one haemosiderosis and only one had cirrhosis of the liver. No correlation was found between the activity of rheumatoid arthritis, and duration of the disease, the drug therapy given, and the liver damage.