Webbing and Delamination of Drug Eluting Stent Coatings.

The advancement of the drug-eluting stent technology raises the significant challenge of safe mechanical design of polymer coated stent systems. Experimental images of stent coatings undergoing significant damage during deployment have been reported; such coating damage and delamination can lead to complications such as restenosis and increased thrombogenicity. In the current study a cohesive zone modeling framework is developed to predict coating delamination and buckling due to hinge deformation during stent deployment. Models are then extended to analyze, for the first time, stent-coating damage due to webbing defects. Webbing defects occur when a bond forms between coating layers on adjacent struts, resulting in extensive delamination of the coating from the strut surfaces. The analyzes presented in this paper uncover the mechanical factors that govern webbing induced coating damage. Finally, an experimental fracture test of a commercially available stent coating material is performed and results demonstrate that the high cohesive strength of the coating material will prevent web fracture, resulting in significant coating delamination during stent deployment.

Micro-scale testing and micromechanical modelling for high cycle fatigue of CoCr stent material.

This paper presents a framework of experimental testing and crystal plasticity micromechanics for high cycle fatigue (HCF) of micro-scale L605 CoCr stent material. Micro-scale specimens, representative of stent struts, are manufactured via laser micro-machining and electro-polishing from biomedical grade CoCr alloy foil. Crystal plasticity models of the micro-specimens are developed using a length scale-dependent, strain-gradient constitutive model and a phenomenological (power-law) constitutive model, calibrated from monotonic and cyclic plasticity test data. Experimental microstructural characterisation of the grain morphology and precipitate distributions is used as input for the polycrystalline finite element (FE) morphologies. Two microstructure-sensitive fatigue indicator parameters are applied, using local and non-local (grain-averaged) implementations, for the phenomenological and length scale-dependent models, respectively, to predict fatigue crack initiation (FCI) in the HCF experiments.

ZNF217, a candidate breast cancer oncogene amplified at 20q13, regulates expression of the ErbB3 receptor tyrosine kinase in breast cancer cells.

Understanding the mechanisms underlying ErbB3 overexpression in breast cancer will facilitate the rational design of therapies to disrupt ErbB2-ErbB3 oncogenic function. Although ErbB3 overexpression is frequently observed in breast cancer, the factors mediating its aberrant expression are poorly understood. In particular, the ErbB3 gene is not significantly amplified, raising the question as to how ErbB3 overexpression is achieved. In this study we showed that the ZNF217 transcription factor, amplified at 20q13 in ∼20% of breast tumors, regulates ErbB3 expression. Analysis of a panel of human breast cancer cell lines (n = 50) and primary human breast tumors (n = 15) showed a strong positive correlation between ZNF217 and ErbB3 expression. Ectopic expression of ZNF217 in human mammary epithelial cells induced ErbB3 expression, whereas ZNF217 silencing in breast cancer cells resulted in decreased ErbB3 expression. Although ZNF217 has previously been linked with transcriptional repression because of its close association with C-terminal-binding protein (CtBP)1/2 repressor complexes, our results show that ZNF217 also activates gene expression. We showed that ZNF217 recruitment to the ErbB3 promoter is CtBP1/2-independent and that ZNF217 and CtBP1/2 have opposite roles in regulating ErbB3 expression. In addition, we identify ErbB3 as one of the mechanisms by which ZNF217 augments PI-3K/Akt signaling.

Return to play after cervical spine injury.

STUDY DESIGN: A questionnaire survey was mailed to members of the Cervical Spine Research Society, the Herodiuus Sports Medicine Society, and to members of the authors' Department of Orthopaedics. OBJECTIVES: The purpose of our study was to evaluate what influence, if any, factors such as published guidelines, type of sport of the patient, number of years in practice, subspecialty interest, and sports participation of the respondent held in the "return to play" decision-making process after a cervical spine injury. SUMMARY OF BACKGROUND DATA: The consequences of cervical spine injury are potentially catastrophic, and return to play decisions in athletes with a history of neck injury can be agonizing. Although recent publications have addressed some of the concerns regarding cervical spine injuries in the athletic population, many questions remain unanswered. Factors such as published guidelines, type of sport of the patient, number of years in practice, subspecialty interest, and sports participation of the respondent have all been suggested as having a possible role in return to play decisions. METHODS: Representative radiographs and case histories of 10 athletes who had sustained neck injury were mailed to 346 physicians. For each case physicians selected every type of play (of six categories) that they felt comfortable recommending. Type of play was divided into six categories: Type 1, collision sports; Type 2, contact sports; Type 3, noncontact, high velocity sports; Type 4, noncontact, repetitive load sports (e.g., running); Type 5, noncontact, low impact sports; Type 6, no sports. In addition, demographic data regarding board certification, subspecialty interest, number of years in practice, use of guidelines in return to play decisions, and personal participation in sports were queried from all respondents. Statistical analysis was completed with Statview (Berkeley, CA). Basic descriptive statistics, chi2, and ANOVA were used where appropriate. RESULTS: Three hundred forty-six questionnaires were mailed and 113 were returned (response rate 32.7%). One hundred ten (97%) of the respondents who completed the questionnaire were board certified. Seventy-five were subspecialists in spine, 22 were subspecialists in sportsmedicine, and 13 reported interests in both sports medicine and spine. Use of Published Guidelines. Although 49% of respondents reported using guidelines in decision-making, the use of guidelines was statistically significant in only one case (P = 0.04). Hierarchy of Risk. In general, those physicians who participated in the study followed the hierarchy of risk that we established in this study (Type 1 [collision sports; highest level of risk] through Type 6 [no sports; lowest level of risk]). Twelve (10.6%) respondents, however, deviated from it in one or more cases. Years in Practice. In three cases there was a statistically significant association between the number of years a physician was in practice and the type of play selected (P < 0.05). In each case a lower level of play tended to be recommended by more senior physicians. Subspecialty Interest. In three cases those respondents with a spine subspecialty interest recommended returned to a higher level of play (P < 0.05). CONCLUSIONS: There is no consensus on the postinjury management of many cervical spine-injured patients. Further research, education, and discussion on this topic are needed.

Recurrent laryngeal nerve injury with anterior cervical spine surgery risk with laterality of surgical approach.

STUDY DESIGN: A detailed review of anterior cervical fusion procedures from a university-based spine specialty service was completed. Noted were the laterality of approach, number of levels, discectomy or corpectomy, use of instrumentation, and cases of reoperation. OBJECTIVES: The primary purpose of the study is to determine whether there is in fact a greater risk of recurrent laryngeal nerve (RLN) injury with approach on the right or left side. Also evaluated is the risk with corpectomy, reoperative procedures, and instrumentation. BACKGROUND: Anatomic considerations have been used as justification to determine the side of surgical approach. However, few clinical studies have delineated the side of surgical approach in their results. METHODS: A total of 328 anterior cervical spine fusion procedures completed between 1989 and 1999 were reviewed. All speech changes reported were noted throughout follow-up. RESULTS: There were 187 anterior discectomy and 141 corpectomy procedures. There were 21 reoperative anterior fusions. There were 173 procedures completed from the right side and 155 from the left. There were nine patients documented to have dysphonia after surgery. Five had a left-sided approach and four had a right-sided approach. CONCLUSIONS: The incidence of RLN symptoms after surgery was 2.7% (9 of 328). The incidence of RLN symptoms was 2.1% with anterior cervical discectomy, 3.5% with corpectomy (5 of 141), 3% with instrumentation (8 of 237), and 9.5% with reoperative anterior surgery (2 of 21). There was a significant increase in the rate of injury with reoperative anterior fusion. There was no association between the side of approach and the incidence of RLN symptoms.

Traumatic atlantoaxial distraction injury: a case report.

STUDY DESIGN: Case report. OBJECTIVES: Description of a rarely reported variant of traumatic C1-C2 dislocation and discussion of a favorable outcome in a nonsurgical treatment approach. SUMMARY OF BACKGROUND DATA: Atlantoaxial dislocation most commonly involves an anterior movement of C1 in relation to C2. Often, the integrity of the transverse ligament or odontoid process is compromised, and the atlantodental interval changed. The described patient sustained a purely craniocaudal atlantoaxial distractive lesion secondary to injury sustained in a high-speed motor vehicle accident. RESULTS: The initial treatment plan involved surgical stabilization subsequent to healing of a C1 ring fracture. After 12 weeks of external stabilization, ligamentous damage appeared well resolved. That there was no gross instability delayed using a surgical option. At periodic checkup, the patient was without symptoms. CONCLUSION: In this case, conservative management of a ligamentous C1-C2 injury was effective. At 5 years after trauma the patient was without sequelae. This outcome is in contrast to previous management of injuries of this type, all of which involved surgical intervention.

Variation in the posterior vertebral contour line at the level of C-2 on lateral cervical roentgenograms: a method for odontoid fracture detection.

As an aid to the assessment of alignment and lordosis, four contour lines can be drawn on the lateral radiograph of the cervical spine. One of these contour lines is the posterior vertebral contour line, in which a smooth, gentle curve, convex anteriorly, is formed by a line drawn along the posterior margins of the cervical vertebral bodies. It is unknown whether discontinuity in the posterior contour line at this level represents a pathologic process of the odontoid. We analyzed the posterior cortex of C-2 and the odontoid in 500 lateral cervical spine radiographs to determine the amount of step-off (deviation from the posterior contour line) seen in normal lateral cervical roentgenograms. Only 15% (n = 75) showed any step-off; none exceeded 3 mm. We recommend that patients presenting with a history of cervical spine trauma who have a step-off at the posterior contour line at the odontoid/C-2 level of > or =3 mm should have fine-cut tomography or multiplanar computed tomography scanning to further assess the odontoid process and rule out fracture.

Functional outcome of low lumbar burst fractures. A multicenter review of operative and nonoperative treatment of L3-L5.

STUDY DESIGN: A retrospective review of 42 patients treated at three major medical centers for burst fractures of L3, L4, and L5. This is the largest low lumbar (L3-L5) burst fracture study in the literature to date. The study was designed to assess both radiographic and clinical outcomes in a cohort of patients treated during a 16-year period. OBJECTIVES: The objective of this study was to determine whether conservatively treated patients with low lumbar burst fractures had satisfactory outcomes compared with those in a surgically treated cohort of patients. The study included patients with and without neurologic deficits. SUMMARY OF BACKGROUND DATA: Burst fractures of the low lumbar spine (L3-L5) represent a small percentage of all spine fractures. The iliolumbar ligaments and location below the pelvic brim are two stabilizing factors that are unique to these fractures when compared with burst fractures at the thoracolumbar junction. METHODS: Forty-two (n = 42) patients with low lumbar burst fractures were identified from 1980 through 1996. Medical records, radiographs, and follow-up Dallas Pain Questionnaires were obtained. Loss of anterior vertebral height, kyphotic angulation, and amount of retropulsion were recorded at several phases of treatment. Mean follow-up time was 45.2 months (range, 5-132 months). Twenty patients were treated without surgery (18 were neurologically intact, and 2 had isolated nerve root injury), and 22 underwent surgery (14 had neurologic injury, 8 were intact). RESULTS: No patient showed neurologic deterioration, regardless of treatment. Fracture of the third lumbar segment showed the greatest tendency toward kyphotic collapse and loss of height in the nonoperative group, although this was not reflected in the final functional outcome of both groups. The ability to return to work and achieve a good-to-excellent long-term result was not significantly different among fracture levels or between surgical and nonsurgical treatments. CONCLUSIONS: The results of nonoperative treatment of low lumbar burst fractures were comparable with those of operative treatment. The rate of repeat surgery (41%) and absence of a clearly definable long-term functional or radiographic benefit in patients without neurologic compromise may make surgery less appealing.

P-31 changes as a measure of therapy response in resistant and sensitive osteosarcomas implanted into nude mice.

OBJECTIVE: To determine if changes in PCr/Pi and PME can be used to predict lack of tumor response to chemotherapy in a murine model of a chemotherapy-resistant human osteosarcoma. MATERIAL AND METHODS: Cisplatin-resistant sublines were grown from high-grade cisplatin-sensitive human osteosarcoma. Surface coil localized 31P NMR spectroscopy of implanted cisplatin-resistant and sensitive osteosarcoma tumors in nude mice was performed. RESULTS: A cisplatin-resistant subline of a sensitive human osteosarcoma was developed that was five times more resistant to cisplatin than the parent cell line. Our NMR data shows a statistically significant difference in the change in the PCr/Pi ratio after treatment between sensitive and resistant osteosarcomas at the alpha = 0.05 level. Changes in PME were seen in the sensitive tumors but were not statistically significant. CONCLUSIONS: Changes in PCr/Pi predict lack of tumor treatment response in human osteosarcoma implanted into nude mice with a specificity of 70% and a sensitivity of 54%. Monitoring of PCr/Pi in human osteosarcoma patients may allow detection of response to chemotherapy before conventional imaging techniques.

Fetal growth response to total parenteral nutrition in pregnancy. A case report.

Although clinical experience with total parenteral nutrition (TPN) in pregnancy is accumulating, assessment of the fetal growth response to this therapy has been limited primarily to birth weight. We performed serial ultrasonographic measurements of the fetal biparietal diameter (BPD), femur length (FL) and abdominal circumference (AC) in a patient who received TPN because of chronic malnutrition. BPD and FL were within normal limits before and after TPN. Consistent with asymmetric growth retardation, the AC was low prior to TPN and increased significantly after TPN was administered. Estimated fetal weight increased accordingly. These data suggest that TPN can reverse subnormal fetal growth secondary to maternal nutritional deprivation.

Altered sensitivity to an opiate antagonist, naloxone, in hyperprolactinemic male rats.

An increase in endogenous opiatergic tone has been suggested as a mechanism for suppression of gonadotropin release in hyperprolactinemia (hyperPRL). In an attempt to evaluate this possibility in hyperprolactinemic males, we have examined the effects of a specific opiate antagonist, naloxone, on plasma LH levels in adult male rats rendered hyperprolactinemic by transplanting two pituitary glands underneath the kidney capsule. Naloxone was administered intravenously (i.v.) at different dose levels (0.2,2, or 20 mg/kg body weight) and blood samples were collected at intervals ranging from 15 to 60 min after naloxone administration. In all experiments, plasma LH levels in the sham-operated controls were significantly increased after naloxone administration, while those in the pituitary-grafted group remained unaltered. Injecting naloxone daily for 3 or for 10 days failed to alter plasma LH levels in both sham-operated and pituitary-grafted animals. Administration of LHRH induced a 7-fold increase in plasma LH levels in both the pituitary-grafted animals and the sham-operated controls. These studies demonstrate that hyperPRL interferes with the naloxone-induced rise in circulating LH levels in the male rat.

Time course of induction of prolactin-secreting pituitary tumors with diethylstilbestrol in male rats: response of tuberoinfundibular dopaminergic neurons.

3,4-Dihydroxyphenylalanine (Dopa) accumulation and dopamine (DA) and noradrenaline levels were measured in the median eminence (ME) of Fisher 344-derived inbred male rats. These animals had been treated with Silastic capsules containing 8-9 mg diethylstilbestrol (DES) or with empty capsules for 3, 7, 14, or 30 days and had the pellets removed 22 days before killing. In an additional group of rats, the DES pellets were continuously present until killing. Blood was collected before treatment was started, at pellet removal, 2 days before killing, and at killing. All rats received 50 mg/kg hydroxybenzylhydrazine (NSD-1015), an L-aromatic amino acid decarboxylase inhibitor, iv 30 min before killing, and the subsequent accumulation of Dopa provided an indirect measure of DA synthesis. Treatment with DES for 7, 14, or 30 days produced an elevation of circulating PRL. Although this elevation of PRL levels was substantially reduced after pellet removal, this parameter was still elevated in the 30-day DES-treated rats at the time of killing. Pituitary levels of PRL and PRL secretion in vitro were elevated in both the 14- and the 30-day DES-treated rats. Rats treated continuously with DES had markedly elevated circulating PRL levels, and the pituitary content and in vitro release of this hormone were also enhanced. DA synthesis, as evidenced by the accumulation of Dopa after NSD-1015 treatment, was significantly elevated in the ME of rats treated with DES for 14 or 30 days while the concentration of DA was reduced in the 30-day treated rats. DA synthesis in the ME was not different from controls in rats treated continuously with DES, although DA levels were markedly suppressed. Pituitary weights were elevated, and BWs were reduced in rats continuously treated with DES. Pituitary weights were also elevated in rats treated with DES for 30 days although not as much as in rats treated continuously with DES. A progressive reduction in seminal vesicles and testes weights was observed with longer periods of DES treatment. Testosterone levels were suppressed in rats treated continuously with DES. In a second study in which rats received DES pellets for 2 months and then the pellets were removed for 4 months, 1 mg bromocriptine sc markedly suppressed the elevated levels of circulating PRL. Collectively, these results show that 14 to 30 days of DES treatment are sufficient to induce PRL-secreting adenohypophysial tumors in adult male rats, although considerable involution of the tumor appears to occur after pellet removal.(ABSTRACT TRUNCATED AT 400 WORDS)

Hyperprolactinemia inhibits development of Leydig cell tumors in aging Fischer rats.

In inbred CDF (Fischer 344) male rats autopsied at the age of 18-24 months, testicular tumors were present in 24 of 36 control animals but in none of 28 males rendered hyperprolactinemic by transplantation of anterior pituitaries from adult females under the renal capsules. In another experiment, microscopically detectable Leydig cell adenomas were present in each of 11 control animals at the age of 14.5 months but in none of 11 males in which hyperprolactinemia was induced by treatment with diethylstilbestrol. Development of testicular tumors had initially little effect on basal and hCG-stimulated plasma testosterone and androstenedione levels but eventually led to atrophy of the seminal vesicles. Incubated tumor tissue produced large quantities of progesterone and responded to hCG in vitro by an increase in progesterone but not testosterone secretion. Daily sperm production and epididymal sperm reserves were significantly reduced already during early stages of Leydig cell tumor development. We propose that hyperprolactin prevents development of Leydig cell tumors by suppression of plasma LH levels and suggest that age-related reductions in gametogenic and steroidogenic functions of the testes in Fischer rats are due to development of Leydig cell tumors rather than to aging per se.