Recanalization of Chronically Occluded Coronary Arteries: Single-Center Experience in 400 Cases, Including Long-Term Angiographic Follow-Up

The study presented comprises the initial and angiographic long-term results of a consecutive series of recanaliza-tion procedures in a single center. Between 1988 and 1992, a total of 400 patients underwent transluminal recanalization for total coronary occlusions. In 82% of successfully attempted patients, the occlusion could be passed by a standard guidewire. The overall initial success rate was 75% (298 of 400). The highest success rates could be achieved in the left circumflex artery (84%) and left anterior descending coronary artery (77%). Complications were uncomplicated myocardial infarction in ten patients (2.5%) and death in two patients (0.5%). Angiographic follow-up 3–6 months after recanalization could be achieved in 263 (88%) of 298 patients. Significant restenosis (≥ 50% minimum lumen diameter) was found in 57 (22%) of 263, and reocclusion was present in 38 (14%) of 263 patients, resulting in a total recurrence rate of 36%. In conclusion, recanalization can be performed with an initial success rate of 75% using bare-wire technique under the prerequisite operator experience. If a nearly complete angiographic follow-up is performed, the overall recurrence rate is 36%, which seems to be very acceptable in comparison with PTC A results for incomplete obstructions published so far . (J Interven Cardiol 1996;9:73–79)     

Epidemiology of low bone mineral density and fractures in children with severe cerebral palsy: a systematic review

Aim  Children with severe cerebral palsy (CP) are at risk for developing low bone mineral density (BMD) and low-impact fractures. The aim of this study was to provide a systematic literature review of the epidemiology of fractures and low BMD in children with severe CP, with an emphasis on risk factors. Gross Motor Function Classification System (GMFCS) levels IV and V were criteria for severe cerebral palsy.
Method  The literature (PubMed) was searched and eligible studies were given a level of evidence score using the Scottish Intercollegiate Guidelines Network criteria.
Results  Seven studies were found concerning epidemiology of fractures, 11 studies described epidemiology of low BMD, and 14 studies concerned risk factors. The methodological quality of most of these studies was poor. Five studies were considered well-conducted with low risk of confounding and bias. In these studies, the incidence of fractures in children with moderate to severe CP approached 4% per year, whereas the prevalence of low BMD in the femur was 77%. Limited ambulation, feeding difficulties, previous fractures, anticonvulsant use, and lower body fat mass were associated with low BMD z-scores.
Interpretation  There is only a limited amount of high-quality evidence on low BMD and fractures in children with severe CP.     

Unrelated donor bone marrow transplantation for children and adolescents with aplastic anaemia or myelodysplasia

Allogeneic transplantation from an HLA-matched family member has been shown to be effective in reconstituting normal haemopoiesis in young people with severe cytopenias, classified as myelodysplastic syndrome (MDS) or severe aplastic anaemia (SAA). Unrelated donor transplant is a therapeutic choice for patients without a suitable family member donor. We report the outcome of seven patients < 20 years old with SAA and 10 with MDS treated with BMT from an HLA A,B DRB1 matched ( n  =8) or A or B locus mismatched ( n  =9) unrelated donor at the University of Minnesota between March 1988 and August 1995. Primary graft failure occurred in two patients and secondary graft failure in one, who was subsequently successfully engrafted with a second donor marrow infusion. Grades II–IV GVHD occurred in 10/16 (63%), and grades III–IV in 6/16 (37%) evaluable patients. Nine of the 17 patients (six with MDS and three with SAA) survive with full donor chimaerism, a median of 1.2 years post-BMT (range 3 months to 7 years). We recommend early referral for consideration of unrelated donor BMT for young patients with MDS, and patients with SAA without response to immunosuppression.     

Induction of macrophage activation and opsonizing antibodies by Trypanosoma cruzi subpopulations

Macrophage activation and production of opsonizing antibodies were studied in mice either infected with a lethal and reticulotropic Trypanosoma cruzi strain, RA, or with a non lethal and myotropic strain, CA-I, as well as with a clone, K98 (derived from CA-I), similar to the parental strain. Measurement of macrophage respiratory burst by chemiluminescence disclosed that T. cruzi infection induced an enhancement of the respiratory burst, no matter the parasite subpopulation employed. But, while in mice surviving RA infection the respiratory burst was higher than during the acute period and parasitaemia was efficiently controlled, in mice infected with K98 enhanced respiratory burst coexisted with measurable levels of parasitaemia either at acute or chronic infection periods. Macrophage activation was also proved by enhanced trypanocidal activity in macrophages derived from mice infected with any of the parasite subpopulations. Sera from RA mice opsonized and lysed T. cruzi bloodstream forms efficiently, whereas sera from CA-I or K98 mice neither lysed nor opsonized this parasite stage. All three subpopulations assayed here showed IgG bound to their membranes in vivo and similar capping kinetics, but only antibodies bound to RA parasites invariably triggered lysis. Therefore, the role played by macrophage activation in resistance and control of Pm levels is related to some features of each T. cruzi subpopulation, such as its capacity to invade macrophages and to elicit opsonizing antibodies.     

Modified β-Cyclodextrin (SBE7-β-CyD) with Viscous Vehicle Improves the Ocular Delivery and Tolerability of Pilocarpine Prodrug in Rabbits

The complexation of pilocarpine prodrug, O,O'-dipropionyl-(1,4-xylylene) bispilocarpate, with various β-cyclodextrin (β-CyD) derivatives was studied by the phase solubility method. The effects of coadministered sulphobutyl ether β-CyD (SBE7-β-CyD) with and without poly(vinyl alcohol) (PVA) on the miotic response and eye irritation of the prodrug were investigated in pigmented rabbits. The pilocarpine prodrug formed 1:1 inclusion complexes with variably substituted sulphobutyl ether derivatives of β-CyD (SBE4-β-CyD and SBE7-β-CyD), and 1:1 and 1:2 complexes with hydroxypropyl-β-CyD (HP-β-CyD) at pH 7:4. Coadministered SBE7-β-CyD eliminated the eye irritation due to the pilocarpine prodrug, but also decreased the miotic response. Ocular absorption of the prodrug was improved by increasing the viscosity of prodrug/SBE7-β-CyD solution with PVA without inducing any eye irritation. Eye irritation due to viscous prodrug/SBE7-β-CyD solutions was comparable with isotonic NaCl solution. We conclude that administration of pilocarpine prodrug in viscous SBE7-β-CyD solution decreases substantially eye irritation while ocular absorption is not affected.     

How β2-selective is the adrenoceptor antagonist drug,IPS 339?

Schild plots for the compound (t-butylamino-3-ol-2-propyl)oximino-9-fluorene (IPS 339) have been obtained on isolated intrinsic tone trachea and atria (rate) of guinea-pigs. α-Adrenoceptors and uptakes were inhibited. The Schild plots for IPS 339 on trachea (fenoterol as agonist) and on atria (noradrenaline as agonist) were not superimposed suggesting that IPS 339 was β₂-selective. The slopes of the Schild plots obtained on intrinsic tone tracheal preparations (isoprenaline or fenoterol as agonist), although greater than 1·0, were not significantly different from that on atria (noradrenaline as agonist). From the average separation of these Schild plots on trachea and atria IPS 339 was assessed to be only 3·3 times more active on β₂- than on β₁-adrenoceptors. The experiments in the literature which showed a high β₂-selectivity for IPS 339 (155 fold) were carried out on carbachol-contracted tracheal preparations (isoprenaline as agonist) and the Schild plot obtained had a very low slope which was quite different from that on atria. Therefore, the results illustrate how the quantitative estimate of the selectivity of a β-adrenoceptor antagonist can be misleading when Schild plots with different slopes are compared.     

Review: The Actions and Side Effects of β-adrenoceptor Blocking Drugs

ABSTRACT This review presents information on the autonomic nervous system, with particular reference to the noradrenergic sympathetic nervous system and adrenoceptors. This leads on to a discussion of the mechanism of action of, main effects and side effects of, and contraindications to the use of the β-adrenoceptor blocking drugs. Emphasis is given to the use of timolol eye drops in the treatment of glaucoma and some consideration is given to its possible mechanism of action in the eye. The review is based on a lecture presented to the 4th Australian/International Optometrical Congress, Gold Coast, Queensland, October 1982.