Effect of isoelectric point on biodistribution and inflammation imaging with indium-111-labelled IgG

Electrostatic effects play an important role in protein interactions and may alter the biodistribution of antibodies. To study the effect of molecular charge on the biodistribution and infection imaging properties of human polyclonal immunoglobulin G (IgG), its iso electric point was varied by changing the level of diethylene triamine penta-acetic acid (DTPA) substitution: 0.8, 0.9, 3.7, 5.1 and 5.9 DTPA/IgG. Biodistributions of the different IgG preparations were determined at 10 min, 1, 6, 24, and 48 h post injection in normal rats, and infection imaging properties were determined in rats withEscherichia coli thigh infections. The biodistribution was significantly affected by pl. The immunoglobulin preparations with 0.9 and 3.7 DTPA/IgG showed faster clearance from the circulation and generally lower accumulation in most organs. The images had a target-to-background ratio of approximately 1.3–2.3:1. These results suggest that even though targeting is not affected by the level of DTPA substitutions, preparations with 0.9 and 3.7 DTPA/IgG may be superior imaging agents because of reduced accumulation by background organs.     

Parity and bone mineral density in middle-aged women

A retrospective study was carried out to determine the relationship between parity and bone mineral density (BMD) in middle-aged women. Eight hundred and twenty-five woman aged 41–76 years were recruited from four general practice registers in Cambridge. Subjects were unselected as to their health status. Each subject completed a detailed health questionnaire. Participation rate was 50%. The main outcome measure was BMD measured at the spine (L2–4,n=825) and hip (neck, intertrochanter and Ward's triangle;n=817) by dual-energy X-ray absorptiometry (DXA) using the Hologic QDR-1000 densitometer. It was found that the unadjusted mean BMD was significantly higher at all sites among the parous women (p=0.031 to <0.00001), and remained significantly higher at the femoral neck (p=0.025), intertrochanter (p=0.001) and Ward's triangle (p=0.045) after adjusting for age and body mass index (BMI). Similar findings were seen after stratifying for potential confounding variables. There was a consistent upward trend of BMD with increasing parity at all sites. Parity remained a significant independent predictor of BMD at all sites after controlling for age, BMI, menopausal status, oral contraceptive and hormone replacement therapy use, smoking status and breast-feeding status in multiple linear regression analyses. There was, on average, a 1.0% increase in BMD per live birth. Our findings therefore suggest a positive relationship between parity and bone mass.     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

Anterior tucking of the iris caused by posterior chamber lenses with polypropylene loops

One hundred ten eyes that had extracapsular cataract extraction with posterior chamber lens implantation were examined gonioscopically to ascertain the frequency of anteriorly displaced polypropylene loops "tucking" into the posterior iris surface. The association with iris transillumination defects and the development of postoperative uveitis, hyphema, and raised intraocular pressure were also recorded. Sixty-six eyes (60%) had one or two anteriorly tucked loops; 28 of them (25%) had some associated iris transillumination defect related to the implant. Twenty eyes (18%) developed persistent postoperative uveitis; 15 of them had anteriorly tucked loops. Two eyes had postoperative hyphema and in both these eyes the loops were anteriorly tucked. The means of recognizing and preventing potential complications are discussed.     

A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease

It has been postulated that dehydroepiandrosterone (DHEA) and its sulfate ester, dehydroepiandrosterone sulfate (DHEAS), the major secretory products of the human adrenal gland, may be discriminators of life expectancy and aging. We examined the relation of base-line circulating DHEAS levels to subsequent 12-year mortality from any cause, from cardiovascular disease, and from ischemic heart disease in a population-based cohort of 242 men aged 50 to 79 years at the start of the study. Mean DHEAS levels decreased with age and were also significantly lower in men with a history of heart disease than in those without such a history. In men with no history of heart disease at base line, the age-adjusted relative risk associated with a DHEAS level below 140 micrograms per deciliter was 1.5 (P not significant) for death from any causes, 3.3 (P less than 0.05) for death from cardiovascular disease, and 3.2 (P less than 0.05) for death from ischemic heart disease. In multivariate analyses, an increase in DHEAS level of 100 micrograms per deciliter was associated with a 36 percent reduction in mortality from any causes (P less than 0.05) and a 48 percent reduction in mortality from cardiovascular disease (P less than 0.05), after adjustment for age, systolic blood pressure, serum cholesterol level, obesity, fasting plasma glucose level, cigarette smoking status, and personal history of heart disease. Our conclusions are limited by the single determination of DHEAS levels, but the data suggest that the DHEAS concentration is independently and inversely related to death from any cause and death from cardiovascular disease in men over age 50.     

Plasma vitamin C levels in men and women from different ethnic backgrounds living in England.

BACKGROUND: People of South Asian origin living in the UK have higher death rates due to coronary heart disease than whites. The reasons for these differences are not fully understood. Previous attempts to relate diet to cardiovascular risk in South Asians have been inconclusive. METHODS: We compared the levels of plasma vitamin C in a cross-sectional population-based study of 1018 men and women aged 40-59 (455 men, 563 women, 328 South Asians, 355 of African descent, 335 whites) co-resident in a geographically defined area of South London, when allowing for potential confounders. RESULTS: Fasting plasma vitamin C levels were significantly higher in women, vegetarians, supplement takers and non-smokers. After adjustment for age, body mass index, current smoking, supplement use and vegetarianism the mean plasma vitamin C levels were 38.8 (SE 1.6) mumol/l in white men, 36.5 (1.6) mumol/l in men of African descent and 32.9 (1.5) mumol/l in South Asian men (P = 0.033 by analysis of co-variance). In women the adjusted mean plasma vitamin C levels were 52.4 (1.6) mumol/l in whites, 46.0 (1.4) mumol/l in women of African descent and 37.3 (1.8) mumol/l in South Asians (P < 0.0001 by analysis of covariance). South Asians had lower levels than whites in both men (difference 6.4 [95% CI: 1.5, 11.3] mumol/l) and women (16.8 [95% CI: 11.5, 22.1] mumol/l). South Asian women, but not men, also had lower levels than those of African descent (8.8 [95% CI: 4.5, 13.1] mumol/l). African women, but not men, had lower levels than white women (6.6 [95% CI: 2.3, 10.9] mumol/l). No significant differences were seen between Caribbeans and West Africans or between South Asian Hindus and Muslims. CONCLUSIONS: These data suggest that important dietary differences in vitamin C exist between different ethnic groups living in England. The larger differences in South Asians may contribute to their increased coronary risk.     

Effects of antimetabolite induced cellular growth arrest on fibroblast-fibroblast interactions.

The use of single five-minute applications of antimetabolites during glaucoma filtration surgery has significantly reduced the occurrence of post-operative scarring and bleb failure. However, surgery for some patients is still unsuccessful, despite the use of antiproliferative agents, due to formation of scar tissue at the drainage site. It is not known if cells growth arrested in the treated area with a single application of antimetabolites influence the activity of adjacent non-treated cells. We hypothesise that the activity of non-treated cells recruited to the wound site may be involved in post-operative scarring. The aim of this study was to investigate the effects of antimetabolite induced cellular growth arrest on cell-cell interactions using in vitro techniques.Tenon's capsule fibroblast cultures were growth arrested by exposure for 5 minutes to mitomycin-C (0.001, 0.01 and 0.1 mg ml-1), 5-fluorouracil (0.25, 2.5 and 25 mg ml-1) or phosphate buffered saline (PBS). Following a period of serum-starvation, conditioned media (CM) were subsequently collected from the cells at intervals up to 29 days post-treatment. Correction for cell number was made prior to supplementation of serum-free medium with CM. CM were assessed for ability to support or inhibit normal non-treated fibroblast proliferation, migration and collagen contraction.Conditioned media collected from cells growth arrested with MMC or 5FU stimulated normal fibroblast proliferation, migration and collagen contraction in excess of non-conditioned serum-free medium. Peaks of fibroblast activity in CM differed according to which drug and concentration had originally been given to the treated cells.This study has demonstrated that CM collected from fibroblasts treated for 5 minutes with a range of concentrations of antimetabolites can differentially influence normal non-treated fibroblast activity. This in vitro data suggests that despite entering growth arrest, fibroblasts may still influence the behaviour of other cells via soluble mediators. They may have implications in the clinical setting, in that it may not be sufficient to suppress proliferation alone to prevent fibroblast behaviour associated with scarring after glaucoma filtration surgery.