Adsorption of plasminogen from human plasma to lysine-containing surfaces

The objective of this work is to develop blood-contacting surfaces that will dissolve nascent clots that may begin to form on them. Surfaces were prepared consisting of a polyurethane to which a coating reagent was attached covalently by photochemical methods. The coating reagent was a polyacrylamide with lysine and benzophenone (for photochemical attachment) moieties pendant to the chains. It was hypothesized that via the lysine moieties such surfaces would show specific binding affinity for plasminogen, the principal component of the fibrinolytic system in blood. Surfaces of varying lysine content in which the lysine was bound through the alpha-amino groups, leaving the epsilon-amino groups free, were investigated. A control surface in which the lysine was bound through the epsilon-amino groups was also examined. Advancing water contact angles showed the surfaces to be hydrophilic. Hydrophilicity was found to decrease as the lysine content increased. Adsorption of plasminogen from plasma was studied using radioiodinated plasminogen as a tracer. For the epsilon-lysine surfaces, adsorption increased with increasing lysine content and reached a value of 1.2 microg/cm(2) for the surface with the highest lysine content, that is, in the range expected for a compact monolayer of plasminogen. The control surfaces, which contained either no lysine or lysine in which the epsilon-amino groups were unavailable, adsorbed very small amounts of plasminogen. Immunoblots were obtained for the proteins eluted from the surfaces after incubation with plasma. For the control surfaces, most of the proteins tested for (some 20 in all) were present. However, for the surface containing the highest concentration of epsilon-lysine, only plasminogen was detected in a significant amount. It is concluded that the epsilon-lysine surface adsorbs plasminogen to the exclusion of the other plasma proteins. Studies to examine the fibrinolytic properties of these surfaces will constitute the next phase of this work.     

Clinical risk factors and evaluation of the risk of osteoporosis in clinical practice

Bone health is determined by influences that accumulate over one's entire lifetime. Numerous factors including age, heredity, nutrition, physical activity, sex steroids and other medical problems all influence the possibility of an individual developing osteoporosis. Fractures due to minimal trauma are the important consequence of osteoporosis, but the risk of fractures is also determined by many non-skeletal risk factors such as body size and the frequency of injury. We now have effective therapeutic options to prevent bone loss and to reduce fracture risk. Assessing risk factors for both osteoporosis and for fractures allows clinicians to identify individuals for whom these therapies are most appropriate.     

Recurrent pancreatitis in three patients with chronic idiopathic intestinal pseudo-obstruction

Chronic idiopathic intestinal pseudo-obstruction is a syndrome with substantial morbidity and mortality associated both with the syndrome and with its therapy. Standard therapy has included prokinetic agents and intravenous nutritional support when oral feedings are inadequate to maintain nutriture. We report three children with chronic intestinal pseudo-obstruction who experienced one or more attacks of pancreatitis. Two patients developed pseudocysts. One patient died. All three patients underwent cholecystectomy; one had stones, one had acalculous cholecystitis, and one had a normal gallbladder. All patients received prokinetic agents and total parenteral nutrition as therapy for their pseudo-obstruction. Candidate mechanisms to explain the etiology for pancreatitis in chronic intestinal pseudo-obstruction include biliary dysmotility associated with pseudo-obstruction and excessive cholinergic stimulation due to therapy with prokinetic agents.     

The long-term effect of specific type II 5alpha-reductase inhibition with finasteride on bone mineral density in men: results of a 4-year placebo controlled trial

PURPOSE: We determine the effect of long-term suppression of dihydrotestosterone with finasteride, a specific type II 5alpha-reductase inhibitor, on bone mineral density. MATERIALS AND METHODS: As part of a large (3,040 cases) 4-year, double-blind, placebo controlled trial designed to assess the long-term effects of finasteride in men with benign prostatic hyperplasia, 157 men 46 to 76 years old who were randomized to receive either 5 mg. finasteride or placebo underwent dual energy x-ray absorptiometry of the lumbar spine at baseline and at years 2, 3 and 4. RESULTS: Of 117 patients who had a baseline measurement and at least 1 additional measurement during the study baseline mean plus or minus standard deviation bone mineral density values were 1.12 +/- 0.17 gm./cm.2 in the finasteride group (63) and 1.10 +/- 0.17 gm./cm.2 in the placebo group (54). After 4 years bone mineral density was not different between treatment groups (finasteride 1.14 +/- 0.17 gm./cm.2 and placebo 1.13 +/- 0.18 gm./cm.2). Similar results were obtained for the 33 finasteride and 25 placebo treated patients who completed the study with year 4 bone mineral density measurements. CONCLUSIONS: These data demonstrate that long-term inhibition of type II 5alpha-reductase with finasteride does not adversely affect bone mineral density.     

Practice MRI: Reducing the need for sedation and general anaesthesia in children undergoing MRI

The aim of this study was to evaluate the effectiveness of a practice magnetic resonance unit, in preparing children to undergo magnetic resonance procedures without general anaesthesia (GA) or sedation. The records of children who attended the practice MRI between February 2002 and April 2004 were retrospectively reviewed. Each record was assessed as to whether the child had passed or failed the practice MRI intervention. Those children who were considered to have passed and were proceeded to a clinical non‐GA MRI had the report of the clinical scan reviewed. If the scan had been reported as non‐diagnostic because of movement artefact it was classified as a failed scan, otherwise it was considered a pass. One hundred and thirty‐four children undertook a practice MRI (age range 4.1–16.1 years, median age 7.7 years, 47% boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%) subsequently had a clinical non‐GA MRI and 110/117 (94%) passed (median age 7.8 years, 47% boys). Preparation is a safe and effective method to reduce the need for sedation and GA in children undergoing a clinical MRI scan. It provides a positive medical experience for children, parents and staff, and results in cost savings for the hospital.     

Double blind, placebo controlled study of nedocromil sodium in asthma

After a two week baseline, 209 asthmatic children (mean age 10 years, range 6-17) were randomly allocated to receive 4 mg nedocromil sodium (n = 110) or placebo (n = 99) four times daily for 12 weeks in addition to their current treatment. The children completed daily diary cards and visited the clinic at four week intervals. Statistically significant differences in favour of nedocromil sodium were seen for clinician assessment of asthma severity and diary card symptom scores, pulmonary function and inhaled beta 2 bronchodilator use. Total symptom score decreased by 50% from baseline in the nedocromil sodium group and by 9% in the placebo group during the final four weeks. Nedocromil sodium was considered very or moderately effective by 78% of children/parents (placebo 59%) and 73% of clinicians (placebo 50%). Nausea, headache and sleepiness, and dyspnoea led to withdrawal of one child from nedocromil sodium and placebo treatments, respectively. Reports of sore throat and headache were marginally greater with the nedocromil sodium treatment. It is concluded that nedocromil sodium was both effective and safe in the treatment of asthma in children.