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.

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.

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.

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.

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 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.

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)

Cognitive control of pain: four serendipitous results.

The experiment was designed to determine whether specific cognitive strategies are effective in reducing pain. Subjects were tested either on cold pain or pressure pain. Although the cognitive strategies did not significantly alter pain tolerance or pain intensity, the following four findings emerged: (a) males and females responded in a similar manner to the painful stimuli, (b) both the experimental subjects and the controls had surprisingly high tolerance of pain, (c) subjects typically generated their own thoughts and images to control pain, and (d) subjects responded to cold pain and to pressure pain in a similar manner.

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.

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.

Milk-borne infection of rats with Strongyloides ratti and Nippostrongylus brasiliensis.

The numbers of mature worms which developed in young rats after their mothers were injected with 4000 L3 late in lactation were 1% (Nippostrongylus brasiliensis) and 24% (Strongyloides ratti) of the dose administered. The low value for N. brasiliensis validates the conclusion that milk is a real and important vehicle for infection in S. ratti since possible errors from skin invasion of the young would have been common to both species. The level of mature S. ratti infection in lactating mothers in this experiment was negligible, 97-99% of the adult worms appearing in the offspring. These results may indicate that the milk route is possible with N. brasiliensis even though it is quantitatively insignificant.

Dynamic determinants of the route of larval Strongyloides ratti in lactating rats and the control of experimental error in quantitative studies of milk transmission of skin-penetrating roundworms.

Subcutaneous injection of nursing mothers from day 16 to day 20 post partum with infective larvae of Strongyloides ratti or Nippostrongylus brasiliensis does not result in the development of worms in the litters if 1 h is allowed between injection and resumed nursing and suckling is terminated 24 h later. Thus the low numbers of N. brasiliensis (1% of the dose) which develop in litters after 24 h, 4 day or 5 days suckling when mothers are injected and returned to their young immediately, represent skin invasion and not milk-borne infection. Taking precautions consistent with the foregoing, S. ratti equivalent to 28%, 45%, 45% and 48% of the dose were shown to be transmitted in the milk to suckling rats of 4 mothers injected with 4000 L 3 on day 18 post partum and 72 h before weaning. One mother of the same batch failed to transmit worms (1% of the dose in the litter) and the take in all 5 mothers was insignificant (max. = 3% of the dose versus an average of 21% in controls). Large numbers of S. ratti were subsequently found in the intestines of mothers whose litters were weaned immediately after (21%) or 6 h after (16%) injection, whereas very few (less than 1%) developed in mothers deprived of their offspring 24 h after injection. Dynamic, rather than static, determinants of larval routes inside the host present the only logical basis for an explanation of these facts.

Strongyloides ratti in virgin female rats: studies of oestrous cycle effects and general variability.

There were no differences in mean intestinal worm burdens 8 days after subcutaneous injection of 4000 infective larvae of Strongyloides ratti into rats in dioestrus, pro-oestrus, oestrus and metoestrus. Thus, changes in the hormonal environment of the migrating larvae dependent on the oestrous cycle did not alter the worms' destination or affect their potential for development. In particular, the results are prima facie evidence that prolactin is not, on its own, responsible for the re-orientation of larvae in the tissues of nursing mothers. Other sources of variability in experimental S. ratti infections are analysed and the 'exact dose' technique offered as a corrective for some procedural errors.

Patterns of milk transmission of Strongyloides ratti.

Eight days after mother rats were injected with 4000 infective larvae of Strongyloides ratti at different stages of lactation the numbers of adult worms in their intestines were uniformly low (less than 3% of the dose) compared with unmated controls (mean = 25%). Those in their litters varied from 12% on day 5 to a maximum of 47% on day 17 post partum. These data, which do not correlate with lactational performance, imply that parasite movements in lactating rats are controlled by qualitative, not quantitative, consequences of humoral events. The numbers of worms in litters are concluded to be the result of the interaction of dynamic determinants of larval routes in the mother and changes in the suitability of the neonatal gut as an environment for worm development. The timing of events leading to milk-borne infection is defined. Injected larvae were closely synchronized in their movements, which were completed in 36 h. Larvae experimentally diverted into the mother's tissues during her first lactation were not available for the infection of a second litter.

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.

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.