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.     

Avidity of technetium 99m glucarate for the necrotic myocardium: In vivo and in vitro assessment

Background  Similar to other^99mTc-based infarct-avid agents,^99mTc-glucarate localizes in myocardial infarcts. Whether severely ischemic viable myocytes sequester^99mTc-glucarate is uncertain. To assess the infarct specificity, in vitro and in vivo studies were performed. Methods and Results  H9C2 embryonic rat cardiocytes cultured under normoxia (N) or hypoxia (H) for 24 hours in 7.5 μCi^99mTc-glucarate were compared with necrotic cardiocytes. Mean H/N ratio (3.0±0.004, mean±SD) was significantly less than that of the necrotic/N ratio (39.9±6.5,p<0.01). Reperfused myocardial infarction (MI) in 4 dogs confirmed by²⁰¹Tl, (0.5 to 1.0 mCi) scintigraphy were imaged serially, with simultaneously injected mixture of^99mTc-glucarate and¹¹¹In-antimyosin Fab. Infarcts were detected scintigraphically within 4 to 10 minutes with^99mTc-glucarate.¹¹¹In-antimyosin required more than 1 hour. Myocardial distribution at 5 hours showed a direct correlation between^99mTc-glucarate and¹¹¹In-antimyosin uptake (r=0.99,p<0.0001). Both^99mTc-glucarate (r=−0.777,p<0.0001) and¹¹¹In-antimyosin (r=−0.775,p<0.0001) were inversely related to²⁰¹Tl distribution. Conclusions  The near perfect correlation between^99mTc-glucarate and¹¹¹In-antimyosin uptake (r=0.99) in reperfused canine MI and the insignificant glucarate uptake by viable cardiocytes in vitro attest to the avidity of^99mTc-glucarate for the necrotic myocardium and favor its use as a specific early marker of myocyte necrosis in acute MI. Supported in part by SBIR grant 1R43-HL54410-01 and Molecular Targeting Technology, Inc.     

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.     

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.     

Function of an ophthalmic "accident and emergency" department: results of a six month survey

A retrospective analysis was carried out of all patients attending the casualty department of Southampton Eye Hospital during 1 February to 31 July 1983. During the six month period 8092 patients made a total of 13 544 visits. Of these patients, 6178 were attending the hospital for the first time and 1914 had previously been seen in the outpatient clinic; many did not fall into the category of "accident and emergency." Some 37% of patients were managed by the ophthalmic nurse alone. The findings show that the department was providing a service far in excess of its defined function, which suggests that the structure of the acute ophthalmic services may require change. Certainly the value of the ophthalmic nurse was beyond question, her active participation in management allowing the doctor more time with the more complex clinical problems and thus enhancing efficiency.     

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.     

Expression of vitreous cytokines in proliferative vitreoretinopathy: a prospective study

PURPOSE: Proliferative vitreoretinopathy (PVR) is a major cause of failure of retinal detachment surgery. It is believed to be a wound-healing process in the retina. Many of the cellular functions are influenced by cytokines and growth factors such as interleukins (ILs). The present study was conducted to investigate the presence of transforming growth factor-beta 2 (TGF-beta2), basic fibroblast growth factor (bFGF), IL-1beta, IL-6, and protein in the vitreous of patients with retinal detachment and to determine the value of these mediators in predicting the future development of PVR. METHODS: A prospective study was conducted in 140 consecutive patients with rhegmatogenous retinal detachment in whom vitrectomy was considered necessary. Vitreous samples were analyzed for the presence of TGF-beta2, bFGF, IL-1beta, IL-6, and protein. Patients were then followed up for 3 months for the development of postoperative PVR. RESULTS: The mean levels of TGF-beta2, bFGF, IL-1beta, and protein in the vitreous were significantly higher (P < 0.05) in patients with preoperative PVR compared with those without. The mean levels of TGF-beta2, bFGF, IL-6, and protein in the vitreous were significantly higher (P < 0.05) in patients who had postoperative PVR compared with those who did not. Multivariate logistic regression analysis showed IL-6 and protein to be significant (P < 0.05), independent, predictive risk factors for the development of PVR. CONCLUSIONS: The various cytokines may play a role in the pathobiology of PVR. High vitreous levels of IL-6 and protein were identified as significant risk factors for PVR. A model was developed to predict the probability of development of postoperative PVR in these patients, and it may be used to indicate intravitreal pharmacologic treatment for those at risk.