Pathological analysis of local delivery of paclitaxel via a polymer-coated stent.

BACKGROUND: Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis. Early and late intimal growth and local vascular pathological changes associated with paclitaxel delivered via stents have not been fully explored. METHODS AND RESULTS: Localized drug delivery was accomplished with balloon-expandable stainless steel stents coated with a cross-linked biodegradable polymer, chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel. CSG-coated stents with paclitaxel (42.0, 20.2, 8.6, or 1.5 microgram of paclitaxel per stent), CSG-coated stents without paclitaxel, and uncoated stents (without paclitaxel or CSG) were deployed in the iliac arteries of New Zealand White rabbits, which were killed 28 days after implant. Mean neointimal thickness at stent strut sites was reduced 49% (P<0.0003) and 36% (P<0.007) with stents containing 42.0 and 20.2 microgram of paclitaxel per stent, respectively, versus CSG-coated stents without paclitaxel. However, histological findings suggested incomplete healing in the higher-dose (42.0 and 20.2 microgram) paclitaxel-containing stents consisting of persistent intimal fibrin deposition, intraintimal hemorrhage, and increased intimal and adventitial inflammation. Stents coated with CSG alone (without paclitaxel) had similar neointimal growth as uncoated stents. In a separate group of rabbits killed at 90 days, neointimal growth was no longer suppressed by CSG-coated stents containing 42.0 or 21.0 microgram of paclitaxel CONCLUSIONS: CSG coating appears to be a promising medium for localized drug delivery. Paclitaxel polymer-coated stents reduce neointima formation but are associated with evidence of incomplete healing at 28 days. However, neointimal suppression was not maintained at 90 days.

Pathologic validation of a new method to quantify coronary calcific deposits in vivo using intravascular ultrasound.

Current methods of calcium quantification by intravascular ultrasound (IVUS) measure the arc of calcium using the cross-sectional image at the lesion and at the reference site while neglecting calcium elsewhere. Calcium at these sites may not adequately represent the extent of total epicardial coronary calcium. We devised a new method to quantify calcium as a percentage of the coronary luminal surface. This study examines whether this new method accurately reflects coronary calcium determined by histology. Seventeen postmortem coronary arteries were pressure-fixed and imaged by IVUS using a motorized pullback device. Total plaque-luminal circumferential length and calcified plaque-luminal circumferential length were measured from serial cross-sectional IVUS images every 1 mm. With use of Simpson's method, the total plaque and calcified plaque surface area was then calculated. Histologic sections were stained with hematoxylin-eosin and Movat pentachrome at 3-mm intervals. Calcium was independently quantified by planimetry under light microscopy. Histologic analysis (n = 253 sections) revealed a wide range of calcium (0 to 47 mm2; mean 12 +/- 16 mm3). The IVUS-derived calcified plaque surface area was 17 +/- 23 mm2), which represented 3.1 +/- 4.1% (range 0% to 13.9%) of the total plaque surface area. The histologic and IVUS quantification of calcium by this method was strongly related (r = 0.84, p <0.0001), which was an improvement over current 2-dimensional measures of calcium arc (r = 0.41, p = 0.18). Calculation of calcified plaque surface area from sequential IVUS images appears to accurately reflect the degree of total coronary calcification.

Stent deformation following simulated side-branch dilatation: a comparison of five stent designs.

We aimed to determine the effects of simulated stent side-branch dilatation and subsequent redilatation of the central lumen. Following coronary stent implantation it may be necessary to dilate through the side of a stent to maintain branch patency. Branch dilatation through the side of 3.5-mm-diameter stents (AVE GFX, beStent, Crown, MultiLink, and NIR) was simulated in a plexiglass phantom using 2.5-, 3.0-, 3.5-, and 4.0-mm balloons. In further experiments, the main lumen was redilated with a 3.5-mm balloon after 3.0-mm side-branch dilatation. Thereafter, a 3.5-mm central and a 3.0-mm side-branch balloon were simultaneously inflated ("kissing balloons"). The larger the balloon size used for side-branch dilatation, the greater the distortion of the stent immediately distal to the side-branch, which for a 4.0-mm balloon ranged from 36% +/- 2% (Crown) to 65% +/- 6% (NIR). Central lumen redilatation or kissing balloons abolished this stenosis with little reduction of the side-lumen diameter. The main stent lumen compromise caused by side-branch dilatation can be abolished by main-lumen redilatation or by kissing balloons.

Nighttime bracing for adolescent idiopathic scoliosis with the Charleston Bending Brace: long-term follow-up.

We report long-term experience with the Charleston Bending Brace for treatment of adolescent idiopathic scoliosis. This brace holds the patient in maximal side-bending correction and is worn at nighttime only. Patients included in this prospective multicenter study met all of the following criteria: skeletal immaturity (Risser 0, 1, or 2), curvature >25 degrees before bracing, no prior treatment, and >1-year follow-up since completion of bracing (skeletal maturity or progression to surgery). All curves were monitored and reported. There were 149 structural curves in 98 patients. Sixty-five (66%) patients showed improvement or <5 degrees change in curvature. Seventeen (17%) patients progressed to the point of requiring surgery for their scoliosis. Based on these long-term results and improvement of the natural history of adolescent idiopathic scoliosis, continued use of the Charleston Bending Brace is justified.

Late outcome after coronary artery bypass graft surgery in patients < 40 years old.

BACKGROUND: Randomized trials confirm the long-term efficacy of coronary artery bypass graft surgery (CABG), although there are no randomized data in patients < 40 years old. Because these patients have been reported to have an early recurrence of symptoms, the long-term postoperative outcome was examined. METHODS AND RESULTS: The long-term outcome of patients (n = 221) < 40 years old undergoing CABG at Green Lane Hospital, New Zealand, from 1970 to 1992 was determined. The 30-day mortality rate was 1.8% for initial and 9.5% for redo CABG. The median times to angina or myocardial infarction (recurrent ischemic event), further intervention, and death were 6.0, 9.6, and 14.2 years, respectively. Factors associated with increased late mortality on univariate analysis included end-systolic volume (ESV) > or = 80 mL (P = .004; 10-year mortality 19% versus 39% ESV > or = 80 mL), no internal mammary conduit (P = .01), no lipid-modifying therapy (P = .005), and no postoperative aspirin use (P = .0002); the latter was also associated with increased recurrent ischemic events (P = .04) or increased reintervention (P = .02). On stepwise logistic regression analysis, factors associated with increased late mortality were increasing ESV (P = .004), no internal mammary artery conduit (P = .009), diabetes (P = .04), and no postoperative aspirin (P = .02); the latter was also associated with increased recurrent ischemic events (P = .02). Hypercholesterolemia (> or = 6.5 mmol/L) was present in 65% of patients at presentation and 45% at follow-up. CONCLUSIONS: To attempt to prevent recurrent ischemia or late death, patients < 40 years old who require CABG should receive internal mammary conduits, aspirin, lipid-modifying therapy, therapy to inhibit ventricular dilatation, and strict diabetes management.

Dynamic axial external fixation in the surgical treatment of tibia vara.

Osteotomy is the well-established treatment of Blount's disease (tibia vara), although the types of fixation used vary considerably. The use of dynamic axial external fixation to stabilize osteotomies for tibia vara until solid union occurs without the use of supplemental casting has not been reported by other authors. From 1985 until the present, we have used osteotomy with dynamic axial external fixation as treatment of 31 tibiae in 23 patients. All osteotomies healed and there was no postoperative loss of correction. There was an average correction of 20 degrees between the pre- and postoperative mechanical axis. Advantages of dynamic axial external fixation include ease of application, adjustability, early weight bearing, the ability to lengthen the extremity, and no second operation for removal of hardware. Based on our results, we believe that dynamic axial external fixation is an excellent form of osteotomy stabilization in the surgical treatment of tibia vara.

Microbial utilization of levoglucosan in wood pyrolysate as a carbon and energy source.

The Waterloo Fast Pyrolysis Process (WFPP) can produce an organic liquid high in levoglucosan (1, 6-anhydro-beta-D-glucopyranose) content from suitably pretreated lignocellulosics. A variety of fungi and yeasts were screened for their ability to utilize and ferment this organic liquid. To enhance its fermentability, the pyrolysis tar was posttreated in three different ways: (1) an aqueous extract (lignin removed); (2) activated charcoal treated (lignin and aromatics removed); and (3) acid hydrolysate (lignin and aromatics removed with the levoglucosan hydrolyzed to glucose). Four fungal strains were examined. None grew in the aqueous extract, but all grew equally well in both the activated charcoal treated and the acid hydrolysate, suggesting that the aromatic species were inhibitory to growth. Seven yeast species were examined, two of which did not grow on any of the extracts. Five of the yeast strains grew well on both the aqueous extract as well as the activated charcoal extract. The hydrolysate was optimal in terms of biomass yield and ethanol production. Ethanol yields on the hydrolysate were comparable or better than those on glucose. Ethanol was also produced in the aqueous extract and activated charcoal-treated substrate, but yields were considerably lower than on the hydrolysate or glucose. It is apparent that a wood pyrolysate maximized for levoglucosan can serve as a fermentable substrate, although postpyrolysis clean-up appears necessary.

Nighttime bracing for adolescent idiopathic scoliosis with the Charleston bending brace. Preliminary report.

The authors report their preliminary experience with the Charleston bending brace for the treatment of adolescent idiopathic scoliosis. This brace holds the patient in the position of maximum side bend correction and is worn only at night. Patients in this prospective multicentered study met all the following criteria: skeletal immaturity (Risser 0, 1+, or 2+), curvature greater than 25 degrees before bracing, no prior treatment, and greater than 1-year follow-up since initiation of treatment. There were 191 structural curves in the 139 patients. One hundred fifteen patients (83%) showed improvement or less than 5 degree change in curvature. Twenty-four patients (17%) demonstrated an increase in curvature greater than 5 degrees. Based on these preliminary results, continued use of bending brace treatment at nighttime only is justified for adolescent idiopathic scoliosis. Patients with double curves should be observed closely for increase in compensatory curves.

Malunited forearm fractures in children.

From 1971 to 1986, 80 skeletally immature patients with severe diaphyseal both-bone forearm fractures were treated at Orlando Regional Medical Center. Greenstick, Monteggia, and Galeazzi fractures were excluded. Seventy-nine fractures were managed by closed means. When anatomic reduction could not be obtained, the best position was accepted. There were 47 patients with malunions of whom 39 returned for follow-up evaluation greater than 2 years after injury. They form the basis of this study. There were no delayed unions or nonunions in the entire group. Average follow-up in the group reported was 5 years 9 months (range 2 years to 13 years 10 months). All patients were satisfied with their functional and cosmetic results regardless of age, angulation, complete displacement, or loss of radial bow at time of union. Only nine patients had loss of motion. By our criteria, 36 patients (92%) had good or excellent results, with 32 excellent and four good results. Three patients (8%) had fair results, and there were no poor results. Age at time of injury did not correlate with recovery of motion. Distal fractures were found to have a better prognosis than proximal fractures. Based on the results of this study, closed reduction is the treatment of choice for skeletally immature patients with diaphyseal fractures of the radius and ulna.

Historical antecedents of dental anxiety.

Our data are based on retrospective self-reported answers of college students. To what extent do these answers accurately reflect the feelings of an actual clinical sample of dental patients? Although there is little direct evidence, a number of observations suggest that in the area of dental anxiety, college populations closely approximate the self-reported answers of the general population. The average level of dental anxiety in an actual clinical sample also appears to be remarkably similar to the average level of dental anxiety among a sample of college students. Kleinknecht and Bernstein found that, on a 1 to 5 scale, dental patients reported a mean level of dental anxiety of 2.31, and that when the identical question was used in a college population, the average level of dental anxiety was 2.47. In our sample, the mean level of dental anxiety was a similar 2.4 on a 0 to 6 scale. Obviously, self-reported answers are subject to distortions. However, it is important that these perceptions can still have a powerful bearing on the behaviors and feelings of patients. A number of observations and hypotheses about the historical origins of dental anxiety were confirmed. Some of these findings have direct clinical implications for the prevention of dental anxiety by dentists or treatment by psychologists. For example, high dentally anxious subjects are more concerned with and feel more ashamed about telling their dentist that they are dentally anxious. It may be helpful for dentists to provide an open forum about the patient's concern.(ABSTRACT TRUNCATED AT 250 WORDS)

Acupuncture treatment of chronic back pain. A double-blind placebo-controlled trial.

Acupuncture treatment of chronic low back pain was studied in a placebo-controlled double-blind crossover trial completed by 77 patients. The patients had significantly increased depression, neuroticism, and hypochondriasis scores. Initial pain levels correlated with state-anxiety, depression, pain duration, and abnormal illness behavior measures, as well as with the intake of psychotropic but not analgesic medication. Overall reduction in pain score was 26 percent for acupuncture and 22 percent for placebo treatment; the difference was not significant (p greater than 0.6). Analgesic drug intake was reduced to a similar extent in both groups. During the first phase of treatment, patients receiving acupuncture had a greater but not significantly different reduction in pain rating scores compared with those receiving placebo (t = 0.52; p greater than 0.6). This group showed significantly lower pain scores (p less than 0.05) in the second phase of the trial while receiving placebo treatment. Overall reduction in individual patient's pain score was best predicted by initial pain severity (r = 0.43; p less than 0.001) and psychotropic drug intake (r = 0.37; p less than 0.001). None of the variables tested predicted which patients would specifically respond to acupuncture or placebo.

The effects of psychological factors on recovery from surgery.

This paper has reviewed correlational studies from both inpatient hospital settings and outpatient oral surgery that demonstrate that several psychological factors are related to postsurgical recovery. Examination of these factors indicates that dentists might improve patients' recovery by giving the surgery a more positive meaning (making the outcome seem desirable), improving patients' acceptance of their condition, making patients' expectations more positive and, reducing anxiety about recovery. Other psychological factors may be helpful in identifying patients who need more support, for example, those with higher trait anxiety, vigilant coping behavior, or an internal locus of control. The review of intervention studies indicates that the best preparation techniques include giving positive suggestions and teaching coping techniques. The value of giving increased amounts of information has not been demonstrated. Also, the literature is not conclusive on varying the type of preparation to fit the personality traits of patients.

Myofascial pain-dysfunction syndrome: a psychobiological perspective.

Myofascial pain-dysfunction (MPD) syndrome is a muscle-contraction headache-like pain of the face. In the past this has also been called temporomandibular joint syndrome. This syndrome is thought to be, in part, a stress-related pain. This paper discusses and evaluates the following topics: (1) patient characteristics, (2) etiological hypotheses, (3) experimental models of the syndrome, (4) psychological characteristics of the patients, (5) psychophysiological characteristics of the patients, and (6) relaxation therapies. Future research is also discussed.

Serotonergic activity in man as a function of pain, pain mechanisms, and depression.

Lumbar cerebrospinal fluid levels of 5-hydroxyindoleacetic acid, which are used as indicators of central nervous system serotonergic neuronal activity, were significantly higher in 67 patients with chronic pain and in 32 patients with acute pain (23.6 +/- 3.3 and 23.1 +/- 3.8, respectively) than in 30 patients (8.8 +/- 1.7) who had no pain. However, there was no correlation between levels of 5-hydroxyindoleacetic acid in patients with chronic or acute pain, nor between groups of patients with chronic pain whose pain mechanisms were of psychogenic, sympathetic, somatic, or central origin, based on their responses to differential spinal block; there was also no correlation between levels of depression, as evaluated by the Zung scale, in patients with different types of chronic pain, even though all of these patients were depressed. The elevated levels of 5-hydroxyindoleacetic acid in the depressed patients with chronic pain are not consistent with previous studies on the etiology and types of chronic pain. As recent research indicates that the perception of pain may be modulated by endogenous analgesic systems involving enkephalin and serotonin (5-HT), this study was undertaken to clarify the association between 5-HT activity and nociception. Our findings did show a link between acute noxious stimulation and central increases in serotonergic activity. However, we could not differentiate between pain mechanisms and degree of depression. Our studies did indicate that, because of both the persistence of pain complaints and the increased levels of brain 5-HT activity, the endogenous analgesic systems are not totally effective as natural inhibitors of pain. Furthermore, the increased depression and continued pain in the presence of elevated 5-HT activity in patients with chronic pain may represent a tolerance or decreased responsiveness to 5-HT.

Treatment of the myofascial pain-dysfunction syndrome: psychological aspects.

Myofascial pain-dysfunction syndrome is a stress-related disorder that involves muscle hyperactivity. Psychological treatments should: reduce muscle tension by relaxation procedures, modify the psychological antecedents to the muscle tension, and modify the psychological consequences to the muscle hyperactivity. The scope of the treatment for the myofascial pain-dysfunction syndrome should be commensurate with the scope of the problem. Patients with brief transient pain, usually associated with discrete problems, should have commensurate, brief, limited interventions, such as a relaxation therapy practiced at home via a tape recording. Patients with long-term problems should have commensurate, longer, more extensive interventions that perhaps include modifying the behavior, the antecedents, and the consequences. These issues may be those that predict failure of treatment by the dentist who uses an occlusal therapy as well as the psychologist who uses a relaxation therapy.

The effects of psychological factors and physical trauma on recovery from oral surgery.

This study evaluated the effects of several psychological factors on postsurgical recovery while controlling for and also evaluating the effects of the physical trauma induced by the surgery. Subjects were 38 patients (18 males and 20 females) who were scheduled to have four third molars surgically removed. The psychological factors measured included anxiety and expectations about recovery, trait anxiety, coping behaviors, and health locus of control. Surgical trauma was rated after surgery, and the following aspects of recovery were monitored: postoperative pain, interference with normal function, swelling, and healing. Poorer postoperative recovery was significantly predicted by each of the psychological variables and by higher levels of surgical trauma. In addition, the effects of the psychological variables on recovery were shown to be largely independent of the trauma effects. The data suggest that (a) future studies which give patients more positive expectations and reduce their anxiety about recovery may improve their recovery and (b) the types of patients most in need of preoperative psychological support would be those who have higher trait anxiety, vigilant coping behaviors, or an internal locus of control.