Comparative trial of local pharmacotherapy with L-arginine, r-hirudin, and molsidomine to reduce restenosis after balloon angioplasty of stenotic rabbit iliac arteries

PURPOSE: To determine if local application of L-arginine, r-hirudin, or molsidomine significantly reduces restenosis after balloon angioplasty in stenotic rabbit iliac arteries. MATERIALS AND METHODS: Thirty-one male cholesterol-fed New Zealand white rabbits underwent balloon dilation of both common iliac arteries to induce arterial stenosis. Four weeks later, one stenotic iliac artery was simultaneously dilated and received local application of L-arginine (210 mg/mL, n = 7), r-hirudin (0.5 mg/mL, n = 8), or molsidomine (0.2 mg/mL, n = 8) with a channeled balloon catheter. On the contralateral side, 0.9% saline was injected as a control. In eight sham animals, saline was applied to one iliac artery and balloon dilation to only the contralateral artery. Six weeks after local treatment, vessels were harvested, and computerized morphometric and immunohistologic analyses were performed. RESULTS: Application of drugs resulted in a significant reduction of neointimal area as follows: 53% with L-arginine (1.01 mm(2) vs. 2.17 mm(2), P <.05), 43% with molsidomine (1.04 mm(2) vs. 1.89 mm(2), P <.05), and 20% with r-hirudin (1.79 mm(2) vs. 2.24 mm(2), P <.05). Infusion of saline led to a significant increase (50%, 1.21 mm(2) vs. 1.93 mm(2), P <.05) in neointimal area compared with balloon dilation alone. Immunohistologic findings showed a significant reduction of macrophages (5.0% vs. 10.2%, P <.05) and proliferating cells (6.2% vs. 10.6%, P <.05) in the neointima after local application of L-arginine. CONCLUSION: Reduction of neointimal area was significant for L-arginine and molsidomine but not for r-hirudin. Saline infusion caused significant arterial trauma, resulting in additional neointimal proliferation.     

1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.     

Six-minute walking test in children with ESRD: discrimination validity and construct validity

The six-minute walking test (6MWT) may be a practical test for the evaluation functional exercise capacity in children with end-stage renal disease (ESRD). The aim of this study was to investigate the 6MWT performance in children with ESRD compared to reference values obtained in healthy children and, secondly, to study the relationship between 6MWT performance with anthropometric variables, clinical parameters, aerobic capacity and muscle strength. Twenty patients (13 boys and seven girls; mean age 14.1 ± 3.4 years) on dialysis participated in this study. Anthropometrics were taken in a standardized manner. The 6MWT was performed in a 20-m-long track in a straight hallway. Aerobic fitness was measured using a cycle ergometer test to determine peak oxygen uptake ( \textV^· \textO_\text2peak ) \left( {\mathop {\text{V}}\limits^\cdot {{\text{O}}_{\text{2peak}}}} \right) , peak rate (W_peak) and ventilatory threshold (VT). Muscle strength was measured using hand-held myometry. Children with ESRD showed a reduced 6MWT performance (83% of predicted, p < 0.0001), irrespective of the reference values used. The strongest predictors of 6MWT performance were haematocrit and height. Regression models explained 59% (haematocrit and height) to 60% (haematocrit) of the variance in 6MWT performance. 6MWT performance was not associated with \textV^· \textO_\text2peak {\mathop {\text{V}}\limits^\cdot {{\text{O}}_{\text{2peak}}}} , strength, or other anthropometric variables, but it was significantly associated with haematocrit and height. Children with ESRD scored lower on the 6MWT than healthy children. Based on these results, the 6MWT may be a useful instrument for monitoring clinical status in children with ESRD, however it cannot substitute for other fitness tests, such as a progressive exercise test to measure \textV^· \textO_\text2peak {\mathop {\text{V}}\limits^\cdot {{\text{O}}_{\text{2peak}}}} or muscle strength tests.     

Skeletal muscle alpha-actin synthesis is increased pretranslationally in pigs fed the phenethanolamine ractopamine

Ractopamine [1-(4-hydroxyphenyl-2-(1-methyl-3-(4-hydroxyphenyl)propylamino)ethanol] enhances protein accretion in skeletal muscle (sm) of pigs. Experiments were conducted to elucidate fractional protein synthesis (FSR) and mRNA abundance for alpha-actin in sm of pigs fed a 16% protein diet containing 20 parts/million ractopamine for 21 days. Pigs were infused for 6 h with [14C]lysine (80 microCi/h.pig); after infusion pigs were killed, and longissimus dorsi muscle samples were obtained for RNA isolation and measurement of [14C]lysine incorporation. FSR was determined in vivo by incorporation of [14C]lysine from the muscle free amino acid pool into purified sm alpha-actin. FSR of sm alpha-actin was 55% greater in ractopamine-treated pigs than in controls. Relative mRNA abundance of alpha-actin was determined by dot blot hybridization of 0.1-0.4 microgram RNA to human sm alpha-actin [32P]cDNA probe. Longissimus dorsi alpha-actin mRNA abundance was 2-fold greater in pigs fed ractopamine. Sm RNA was translated in vitro using a cell-free assay to determine pretranslational effects on other muscle proteins. Effects of ractopamine on muscle protein synthesis are not specific to sm alpha-actin, because other muscle proteins also were increased using the in vitro translation assay. These results indicate that the increase in sm accretion in pigs fed ractopamine is due in part to an increase in myofibrillar protein synthesis and that some of the increase can be accounted for by an increase in mRNA abundance for sm alpha-actin.     

Digital imaging of the chest

During the past several years, image acquisition in nuclear medicine, computed tomography, ultrasonography, subtraction angiography, and magnetic resonance has been by digitization. Despite these advances, research in the development of digital imaging in conventional radiography has lagged behind. Although studies with a variety of digital techniques have been carried out on several fronts, we still do not possess a method that has captured the imagination of the majority of radiologists and other physicians to a point where it could replace conventional screen-film imaging. This article reviews the current status and general principles of the technology, focusing on the four digital radiographic techniques that have shown the greatest promise - film digitization, an image intensifier - based system, photostimulable phosphor plates, and a scanned projection system. The physical aspects of each of the four systems and the clinical results that have been reported to date, as well as the advantages and disadvantages of each system, are presented.     

Ultrastructural immunocytochemical localization of B-50/GAP43, a protein kinase C substrate, in isolated presynaptic nerve terminals and neuronal growth cones

Summary Accumulating evidence indicates that the neuron-specific B-50/GAP43, a substrate for protein kinase C, plays a role in neuronal differentiation and neuritogenesis during nervous tissue development and axonal regeneration. An ultrastructural immunocytochemical study on the localization of B-50 in presynaptic terminals (synaptosomes) and neuronal growth cones was carried out by means of cryoultramicrotomy with affinity-purified B-50 antibodies. Detection was accomplished with colloidal gold, conjugated either to protein-A or goat anti-rabbit immunoglobulins. In synaptosomes, isolated from the frontal cortex of 6-week-old rats, and in neuronal growth cones, isolated from forebrains of 5-day-old rats, the majority of B-50 is detected at the surrounding neuronal plasma membrane. In both neuronal growth cones and synaptosomes, a relatively small fraction of B-50 in the cytoplasm was not evidently associated with internal membranes. Our results indicate that B-50 is mainly located at the cytoplasmic face of the synaptosomal and neuronal growth cone plasma membrane. The similar B-50 localization in neuronal growth cones and synaptosomes suggests that, both in extending axons and mature synaptic terminals, B-50 may exert identical functions as a protein kinase C substrate at the plasma membrane.     

Adrenoceptor-mediated mechanical responses of canine tracheal smooth muscle

The effect of tone on responses of canine tracheal smooth muscle (TSM) to norepinephrine (NE) was studied to elucidate the role of sympathetic innervation and adrenoceptors in the control of the airways. Electrical field stimulation produced contraction of TSM in vitro which was augmented by eserine, depressed by phentolamine, potentiated by propranolol in the presence of K+ (14 mM) and almost eliminated by tetrodotoxin or atropine. Resting TSM did not contract in response to NE (10(-8) to 10(-4) M) in the presence or absence of propranolol (10(-5)M). The addition of NE (10(-8) to 10(-6) M) at the plateau of contraction produced by K+ (22.8 mM), histamine (10(-6) M) or acetylcholine (5 X 10(-8) M) produced a further phentolamine-sensitive contraction which was potentiated by beta adrenoceptor blockade with propranolol (10(-5) M). The addition of tyramine (10(-5) to 10(-4) M) at the plateau of contraction produced by K+ (22.8 mM) produced a further contraction which was potentiated by propranolol (10(-5) M) and reduced by phentolamine (10(-5) M). Although the response to NE in the presence of elevated tone was contractile at low concentrations of NE (10(-8) to 10(-6) M), a propranolol-sensitive relaxant response was elicited at higher NE concentrations (10(-5) and 10(-4) M). Maximum contractions to NE in the absence or presence of beta-blockade were dependent on the tone of the muscle. These findings suggest a functional adrenergic innervation of canine TSM and the presence of alpha and beta adrenoceptors which mediate contractile and relaxant responses, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Predictors of Ventricular Tachvcardia Inducibility in Programmed Electrical Stimulation and the Effectiveness of Serial Drug Testing: Polish Multicenter Study

WNUK-WOJNAR, A.M., ET AL.: Predictors of Ventricular Tachycardia Inducibility in Programmed Electrical Stimulation and Effectiveness of Serial Drug Testing: Polish Multicenter Study. In 100 patients with IHD and complex ventricular arrhythmias, programmed electrical stimulation was performed using up to three extrastimuli at sinus rhythm, and paced 100, 120, and 140 beats/min delivered from the RV apex, outflow tract or the LV with ventricular mapping to evaluate late potentials (LP) in 41 patients. Sustained monomorphic VT (SMVT) was provoked in 91% of 42 patients with a history of VT/VF, p < 0.001, all five patients had SMVT in 24-hour ECG, p < 0.005, and 91% of 21 patients with LV dyskinesis, p < 0.01. After depolarizations were found in 62% of 21 patients with a history of VT, in 58% of 31 patients with inducible VT, p < 0.01 and in five of six patients with LV dyskinesis. In patients with inducible VT, LP had a higher amplitude (105 ± 35 vs 60 ± 47 µV) and were more delayed (202 ± 96 vs 133 ± 75 msec) than in noninducible patients. In 17 patients, serial drug testing was performed after oral administration using mexilitene, disopyramide, chinidine, propafenone, sotalol, and amiodarone. If one drug was tested, the therapy efficacy was 25% if two drugs-60%, and if three drugs-75%. In eight patients, VT was inducible in all tests, but in only one of these patients chronic antiarrhythmic therapy was not effective. We conclude that the most important predictors of VT inducibility are a history of VT or 24-hour ECG, and LV dyskinesis. Serial drug testing is efficient only when many drugs are tested, but even if VT is inducible, it does not exclude the possibility of a good clinical outcome in chronic therapy.