Studies of the induction and maintenance of long-term graft acceptance by treatment with FK506 in heterotopic cardiac allotransplantation in rats

Immunosuppressive activities of the newly discovered FK506, isolated from Streptomyces tsukubaensis, were examined by using cardiac allotransplantation in the rat, and the mechanisms underlying induction and maintenance of FK506-induced long-term allograft survival were studied. Male rats of WKA (RT1k) and F344 (RT1lvl) strains were used as recipients and donors, respectively, and those of BN (RT1n) strain were used as third-party donors. Treatment with FK506, beginning from the day of allografting for 14, 10, or as few as 4 days, prolonged allograft survival significantly across the major histocompatibility barrier. The minimum doses for prolonging graft survival were 0.1 mg/kg/day by intramuscular treatment and 1.0 mg/kg/day by oral treatment. Treatment with FK506 at a dose of 0.32 mg/kg/day from day 4 until day 10 resulted in all the grafts surviving indefinitely and from days 5 to 10, half the grafts survived indefinitely, suggesting that the agent inhibited ongoing rejection. On the other hand, cyclosporine treatment at a dose of 20 mg/kg/day from day 2 did not prolong graft survival time statistically significantly. Induction of prolonged graft survival was not obtained by pretreatment of the prospective donor or recipient; prolonging effects were observed only when the agent was administered after allografting. Thus, the primary effect of the agent is exerted on responder lymphocytes reacting to the donor antigens in the induction phase of long-term graft acceptance. The mechanisms underlying the maintenance of long-term grafts were analyzed by testing the capacity of lymphocytes or serum of long-term graft-bearing rats to inhibit graft rejection in irradiated grafted hosts. Transfer of 2 x 10(8) lymphocytes from FK506-induced long-term F344 graft-bearing WKA rats resulted in indefinite survival of F344 heart allografts, but it did not prolong survival of third-party BN hearts. Transfer of 2.5 ml serum from long-term graft-bearing rats also prolonged graft survival of F344 hearts, but not BN hearts. These results suggest that donor strain-specific suppressor cells and humoral factor(s) are induced by treatment with FK506 in the presence of allografts, and that they play at least partial roles in the maintenance of long-term allograft acceptance.     

The pH Optima for Papain and Bromelain Treatment of Red Cells

The action of papain and bromelain, prepared over a pH range from 4.6 to 8.6, was evaluated for the ability to render red cells agglutinable by five incomplete antibodies of differing blood group specificities using a two-stage technique. The optimal pH for treatment of red cells by activated papain or bromelain was between 5.4 and 5.8. Above this pH range, a fall in serological sensitivity was apparent which was much more pronounced with papain than with bromelain. The optimal pH for enzyme treatment of red cells can be achieved in two-stage techniques, but not in one-stage techniques due to the buffering effect of serum proteins.     

An experimental collagen-impregnated dacron graft: Potential for endothelial seeding

This study evaluates the potential for endothelial seeding of a collagen-impregnated Dacron graft with or without surface modifiers (fibronectin, heparin) to attach and retain these cells during flow. Human umbilical endothelial cells were harvested, cultured, labeled with Indium111-oxine and seeded onto 30 mm X 4 mm diameter grafts. Six graft surfaces were studied: 1) a collagen-impregnated Dacron graft, HemashieldR (C); 2) C + fibronectin (C + F); 3) C + heparin (C + H); 4) C + F + H; 5) HytrelR + F (Hyt + F); and 6) Hyt + F + H. Radioactive loss determined the percentage attachment and then percentage retention of labeled inoculum after a one-hour in vitro perfusion. Scanning electron and light microscopy demonstrated the endothelium on the graft surface following perfusion. Fibronectin-coated grafts had a significantly higher percentage attachment than those without fibronectin (ANOVA, P less than 0.05). However, the percentage retention following perfusion was similar for all Dacron grafts and statistically inferior to the HytrelR grafts studied (ANOVA, P less than 0.05). SEM evaluation of the C + F + H graft surface was qualitatively the most impressive Dacron surface for seeding, yet was inferior to the HytrelR graft. We conclude that fibronectin benefits the initial attachment of endothelium to collagen-coated Dacron rivaling the HytrelR surface. Fibronectin does not improve percentage retention of the HemashieldR surface during perfusion, therefore, some of its initial benefit is lost.     

A self-reported survey of Alzheimer's centers in Southwestern Pennsylvania

Directors of nursing at 23 nursing homes with Alzheimer's units in Southwestern Pennsylvania completed a self‐reported survey of 12 questions. Responses from the self‐administered questionnaires (100% response rate) revealed a wide variation in the staff categories assessing the oral health status of newly admitted residents with AD. The respondents described oral examinations that were incomplete when compared to the oral indicators listed in the Minimum Data Set. All nursing homes reported that oral hygiene was provided each day. The number of residents in a facility had a significant effect on the frequency of oral hygiene provided. Only 52% of the facilities reported yearly oral examinations for this population. According to the respondents, dental treatment was typically performed on‐site. The oral health care costs were paid by Medicare, Medicaid, the residents/family members, or by other undescribed resources. Insufficient time, staff, and training, as well as uncooperative behavior, were identified as barriers to optimum oral health care for residents with AD. Additional staff, specialized training, and increased government reimbursement were suggested to improve the oral health care for this group of older adults. For future studies, review of medical records and on‐site evaluation of the oral health care at these facilities should be required to verify the reported practices.     

Reproducibility of food atopy patch tests over time in the general child population

Background  The atopy patch test (APT) is no longer an experimental method; it is increasingly being used as a standard diagnostic tool for the characterization of patients with aeroallergen- and food-triggered disorders. Some technical aspects of this test still remain to be answered. We aimed to study the reproducibility of this test over time in the general child population.
Methods  In a general population of 118 children, we investigated the reproducibility of duplicate APTs with four food allergens in their native form, which were repeated at set intervals from the first test: 7 days (group 1), 14 days (group 2), and 21 days (group 3).
Results  We observed very poor reproducibility on both sides of the back in all three studied subgroups. The reproducibility rates and Cohen's κ values did not improve when we did not consider the side of the back. There were no differences in the prevalence of atopy between the subjects with reproducible and nonreproducible APT results. All three groups studied showed no difference in the prevalence rates of atopy. There was no relationship between APT and skin prick test positivity for the same allergen. Questionnaire-derived data about previous food-related reactions did not help in the evaluation of the doubtful nonreproducible APT results with food allergens.
Conclusions  Our results show that the reproducibility of food APTs is poor and unsatisfactory over time, and there is an urgent need for the development of optimal, stable, and good-quality APT testing substances.     

A randomized,double‐blind,placebo controlled,multi‐center study of intravenous iron sucrose and placebo in the treatment of restless legs syndrome

Iron deficiency may exacerbate symptoms in the Restless Legs Syndrome (RLS). We investigated the effect of intravenous iron sucrose or placebo on symptoms in patients with RLS and mild to moderate iron deficit. Sixty patients with primary RLS (seven males, age 46 (9) years, S‐ferritin ≤45 μg/L) recruited from a cohort of 231 patients were randomly assigned in a 12‐months double‐blind, multi‐centre study of iron sucrose 1000 mg (n = 29) or saline (n = 31). The primary efficacy variable was the RLS severity scale (IRLS) score at week 11. Median IRLS score decreased from 24 to 7 (week 11) after iron sucrose and from 26 to 17 after placebo (P = 0.123, N.S. for between treatment comparison). The corresponding scores at week 7 were 12 and 20 in the two groups (P = 0.017). Drop out rate because of lack of efficacy at 12 months was 19/31 after placebo and 5/29 patients after iron sucrose (Kaplan–Meier estimate, log rank test P = 0.0006) suggesting an iron induced superior long term RLS symptom control. Iron sucrose was well tolerated. This study showed a lack of superiority of iron sucrose at 11 weeks but found evidence that iron sucrose reduced RLS symptoms both in the acute phase (7 weeks) and during long‐term follow up in patients with variable degree of iron deficiency. Further studies on target patient groups, dosing and dosing intervals are warranted before iron sucrose could be considered for treatment of iron deficient patients with RLS. © 2009 Movement Disorder Society