Femoral diaphysis fractures in cattle: 26 cases (1994-2005).

OBJECTIVE: This retrospective study was conducted to evaluate the outcome for cattle with diaphyseal fractures of the femur, but not including capital physeal injuries. METHODS: Sources of information were medical records of cattle having a definitive diagnosis of diaphyseal femoral fractures and telephone survey of owners. RESULTS: Medical records for 26 cattle with femoral fracture were found; of the 20 aged less than 2 months, 15 were treated surgically, 4 conservatively (stall rest) and 1 was euthanased without treatment. The surgical treatment varied according to the configuration of the fracture and the surgeon's experience. Surgery for mid-diaphyseal fractures had a significantly better surgical outcome then distal diaphyseal fractures (P < 0.05), as there were significantly fewer postoperative complications. Of the 15 calves treated surgically, 10 were discharged from hospital and 5 were retained in the herd without noticeable lameness. Of the 4 calves treated conservatively, 3 were alive at follow-up, but 2 were still lame. Of the 6 older cattle, 3 were euthanased without treatment and 3 were treated conservatively, 2 of which were alive at follow-up but 1 was still lame. CONCLUSION: Conservative treatment of femur fracture in cattle is possible but associated with complications during the convalescence. Continued research is needed to optimise distal diaphyseal fracture stabilisation in young cattle.

Sleep patterns and daytime sleepiness in adolescents and young adults with Williams syndrome.

BACKGROUND: Sleep disorders are common in individuals with neurodevelopmental disorders and may adversely affect daytime functioning. Children with Williams syndrome have been reported to have disturbed sleep; however, no studies have been performed to determine if these problems continue into adolescence and adulthood. METHODS: This study examined overnight sleep patterns and daytime sleepiness in 23 adolescents and adults with Williams syndrome age 25.5 (8.0) years [mean (SD)]. Interviewer-administered sleep questionnaires were used to evaluate nighttime sleep behaviours and daytime sleepiness. Wrist actigraphy was used to evaluate sleep patterns. RESULTS: Although individuals in our sample averaged 9 h in bed at night, daytime sleepiness and measures of sleep disruption were common and comparable to those of other populations with neurodevelopmental disorders. These measures included reduced sleep efficiency [74.4 (7.0)%] with prolonged sleep latency [37.7 (37.3) min], increased wake time after sleep onset [56.1 (17.6) min], and an elevated movement and fragmentation index [14.3 (4.6)]. CONCLUSION: Adolescents and young adults with Williams syndrome were found to be sleepy despite averaging 9 h in bed at night. Implications are discussed for associated causes of sleep disruption and future polysomnographic evaluation.

Bioactive hydrogel-filament scaffolds for nerve repair and regeneration.

The design of novel biomaterials is crucial for the advancement of tissue engineering in nerve regeneration. In this study we developed and evaluated novel biosynthetic scaffolds comprising collagen crosslinked with a terpolymer of poly(N-isopropylacrylamide) (PNiPAAm) as conduits for nerve growth. These collagen-terpolymer (collagen-TERP) scaffolds grafted with the laminin pentapeptide YIGSR were previously used as corneal substitutes in pigs and demonstrated enhanced nerve regeneration compared to allografts. The purpose of this project was to enhance neuronal growth on the collagen-TERP scaffolds through the incorporation of supporting fibers. Neuronal growth on these matrices was assessed in vitro using isolated dorsal root ganglia as a nerve source. Statistical significance was assessed using a one-way ANOVA. The incorporation of fibers into the collagen-TERP scaffolds produced a significant increase in neurite extension (p<0.05). The growth habit of the nerves varied with the type of fiber and included directional growth of the neurites along the surface of certain fiber types. Furthermore, the presence of fibers in the collagen-TERP scaffolds appeared to influence neurite morphology and function; neurites grown on fibers-incorporated collagen-TERP scaffolds expressed higher levels of Na channels compared to the scaffolds without fiber. Overall, our results suggest that incorporation of supporting fibers enhanced neurite outgrowth and that surface properties of the scaffold play an important role in promoting and guiding nerve regeneration. More importantly, this study demonstrates the potential value of tissue engineered collagen-TERP hybrid scaffolds as conduits in peripheral nerve repair.

Effect of LVAD outflow conduit insertion angle on flow through the native aorta.

BACKGROUND AND AIM: The goal of this study was to evaluate the effect of surgical anastomosis configuration of the aortic outflow conduit (AOC) from a continuous flow left ventricular assist device (LVAD) on the flow fields in the aorta using CFD simulations. The geometry of the surgical integration of the LVAD is an important factor in the flow pattern that develops both in series (aortic valve closed, all flow through LVAD) and in parallel (heart pumping in addition to LVAD). METHODS: CFD models of the AOC junctions simulate geometry as cylindrical tubes that intersect at angles ranging from 30 degrees to 90 degrees. Velocity fields are computed over a range of cardiac output for both series and parallel flow. RESULTS: Our results demonstrate that the flow patterns are significantly affected by the angle of insertion of the AOC into the native aorta, both during series and parallel flow conditions. Zones of flow recirculation and high shear stress on the aortic wall can be observed at the highest angle, gradually decreasing in size until disappearing at the lowest angle of 30 degrees. The highest velocity and shear stress values were associated with series flow. CONCLUSIONS: The results suggest that connecting the LVAD outflow conduit to the proximal aorta at a shallower angle produces fewer secondary flow patterns in the native cardiovascular system.

Lessons learned from a failed multi-institutional randomized controlled study.

BACKGROUND/PURPOSE: In 1996, the Surgical Sections of the Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG) received National Cancer Institute funding to conduct a prospective, randomized, controlled, surgeon-directed study to evaluate the role of minimally invasive surgery (MIS) in children with cancer. Because of lack of patient accrual, the study was closed in 1998. The purpose of this study is to evaluate and describe those factors that impacted on study failure to ensure future successful clinical trials. METHODS: One hundred forty surgeons representing the surgical membership of CCG and POG as well as 111 institutions within CCG and POG were asked to complete a questionnaire about the failed clinical trial. The questionnaire focused on study objectives, organization, and institutional review board (IRB) submission. It also examined the surgeon's ability to perform the minimal access operation, the influence of the pediatric oncologist, and the existence of preconceived biases by surgeons, oncologists, and families. Statistical analysis was performed as appropriate. RESULTS: Eighty-six of 140 (62%) surgeons responded to the questionnaire. Only 23% of the potential protocols were submitted for IRB approval. Of responding surgeons, 39% were not actively performing MIS when the study opened. A surgeon's support of the study was directly related to when the surgeon received the protocols (P <.001) and whether the participating surgeon was actively participating in MIS (P <.016). The oncologist's knowledge and support of the study affected IRB submission and approval (P <.02) and was influenced by whether MIS was practiced at the institution (P <.05). The majority of responding surgeons believed the experimental question was relevant (P <.05). However, responding surgeons believed that a preconceived bias existed within both their local surgical and oncology communities favoring a particular surgical approach (P <.001), but this bias did not extend to the families (P >.05). CONCLUSION: The study failed because of lack of accrual for a variety of reasons: failure to submit to the institution's IRB, lack of surgical expertise with MIS procedures, and preconceived surgeon bias toward either an endoscopic or traditional open approach.

MRI imaging of fetal neck masses with airway compromise: utility in delivery planning.

We present two cases of fetal neck masses that were initially diagnosed by ultrasound and further evaluated with prenatal MRI. MRI findings aided in further delineating the neck masses, increasing confidence in the final diagnosis (cervical teratoma and cystic hygroma). With the fetal airway typically filled with fluid that is of high signal on T2-weighted sequences, MRI images in three planes could identify whether the fetal larynx and trachea were partially or completely compressed by the neck tumor. This information was particularly useful in determining if a controlled delivery such as ex utero intrapartum treatment (EXIT) was necessary and aided the surgeons in planning their approach to establishing airway control in the delivery room.

The use of a bioactive skin substitute decreases length of stay for pediatric burn patients.

BACKGROUND: To optimize burn care for children, the authors introduced a protocol incorporating the use of a bioactive skin substitute, TransCyte (Advanced Tissue Sciences, La Jolla, CA). This study was designed to determine whether this management plan was safe, efficacious, and decreased hospital inpatient length of stay (LOS) compared with conventional burn management in children. METHODS: All pediatric burns greater than 7% total body surface area (TBSA) that occurred after October 1999 underwent wound closure with TransCyte (n = 20). These cases were compared with the previous 20 consecutive burn cases greater than 7% TBSA that received standard therapy. Standard therapy consisted of application of antimicrobial ointments and hydrodebridement. The following information was obtained: burn mechanism, age, size of burn, requirement of autograft, and LOS. Data were analyzed using the student's t test. RESULTS: Data for age, percent TBSA burn and LOS are reported as means +/- SEM. The children who received standard therapy were 2.99 +/- 0.7 years compared with those receiving TransCyte were 3.1 +/- 0.8 years. There was no difference between the treatment groups with regard to percent TBSA burn: standard therapy, 14.3 +/- 1.4% TBSA versus TransCyte, 12.7 +/- 1.3% TBSA. There was no difference in the type of burns in each group, the majority were liquid scald type, 70% in the standard therapy group versus 90% in the TransCyte group. Only 1 child in the TransCyte group required autografting (5%) compared with 7 children in the standard therapy group (35%). Children treated with TransCyte had a statistically 6 significant decreaed LOS compared with those receiving standard therapy, 5.9 +/- 0.9 days versus 13.8 +/- 2.2 days, respectively (P =.002). CONCLUSIONS: This is the first study using TransCyte in children. The authors found that this protocol of burn care was safe, effective, and significantly reduced the LOS. This new approach to pediatric burn care is effective and improves the quality of care for children with burns.

When appendicitis is suspected in children.

Acute appendicitis is the most common condition requiring emergent abdominal surgery in childhood. The clinical diagnosis of acute appendicitis is often not straightforward because approximately one-third of children with the condition have atypical clinical findings. The delayed diagnosis of this condition has serious consequences, including appendiceal perforation, abscess formation, peritonitis, sepsis, bowel obstruction, and death. Cross-sectional imaging with ultrasonography (US) and computed tomography (CT) have proved useful for the evaluation of suspected acute appendicitis. There has been a great deal of variability in the utilization of these modalities for such diagnosis in the pediatric population. The principal advantages of US are its lower cost, lack of ionizing radiation, and ability to assess vascularity through color Doppler techniques and to provide dynamic information through graded compression. The principal advantages of CT include less operator dependency than US, as reflected by a higher diagnostic accuracy, and enhanced delineation of disease extent in a perforated appendix.

Differentiated thyroid cancer: clinical characteristics, treatment, and outcome in patients under 21 years of age who present with distant metastases. A report from the Surgical Discipline Committee of the Children's Cancer Group.

BACKGROUND/PURPOSE: Young patients with differentiated thyroid cancer typically present with regional lymph node involvement (60% to 80%), and 10% to 20% have distant metastases. This study characterizes the clinical presentation, treatment, and outcome in patients with differentiated thyroid cancer who were less than 21 years of age at diagnosis and who presented with distant parenchymal metastases. METHODS: A retrospective, multi-institutional data base that included 327 patients in this age group with differentiated thyroid carcinoma was searched for patients who presented with distant metastases, and 83 cases (25%) were found. The median time to first disease progression was 2.4 years (range, 0.1 to 12.4 years) and the overall median follow-up was 10.9 years (range, 1.0 to 42.1 years). RESULTS: The median age at diagnosis was 14.6 years (range, 6.6 to 20.8 years); 69% were girls and 92% were white. In 12%, there was a history of prior head and neck irradiation, and 10% of these patients had a family history of carcinoma. Preoperative needle biopsies were performed in 25%. Regional lymph nodes were positive in 90%, and extrathyroidal extension occurred in 48%. The site of distant metastases included the lungs in all patients. Total thyroidectomy, subtotal thyroidectomy, lobectomy, and nodule excision was done in 66%, 24%, 3%, and 8% of patients, respectively. There was no residual cervical disease after surgery in 75%, whereas 14% had microscopic and 11% had gross residual. Histopathologic subtypes included papillary-follicular (48%), papillary (42%), and follicular (10%). The median tumor size was 3.0 cm (range, 0.4 to 11.0 cm). In this group, 100% of patients received adjuvant iodine 131I therapy, and the overall survival rate at 10 years was 100%. The progression-free survival rate was 76% at 5 years and 66% at 10 years from diagnosis. CONCLUSIONS: A significant number of young patients with thyroid cancer present with distant metastases and will require radioiodine therapy. This should be considered when planning the surgical approach because total or subtotal thyroidectomy facilitates 131I imaging and treatment. Although about one third of these patients will experience relapse or disease progression, the overall mortality rate is low.

Cytoplasmic delivery of a macromolecular fluorescent probe by poly(d, l-lactic-co-glycolic acid) microspheres.

A macromolecular fluorescent probe encapsulated in poly(d, l-lactic-co-glycolic acid) (PLGA) microspheres was used as a model for studying cytoplasmic delivery of antigens. We hypothesized that Texas red dextran loaded in PLGA microspheres would be delivered to the cytoplasm and that cytoplasmic delivery would be affected by polymer molecular weight. Cellular localization of the Texas red dextran was investigated at two different molecular weights of PLGA: 6000 and 60,000 g/mol. Intracellular degradation and processing of Texas red dextran-loaded PLGA microspheres by mouse peritoneal macrophages was monitored both in vitro and in vivo for a 7-day period using confocal laser scanning microscopy (CLSM). The results revealed cytoplasmic delivery of the fluorescent probe at both molecular weights of PLGA. Furthermore, the CLSM images showed that both in vitro and in vivo, the kinetics of microsphere degradation and cytoplasmic delivery were more rapid for the 6000 g/mol PLGA microspheres than the 60,000 g/mol PLGA microspheres. Hence, this study provides physical evidence that PLGA microspheres are capable of cytoplasmic delivery and that delivery to the cytosol can be controlled by modifying formulation parameters such as polymer molecular weight.

Delivery of MUC1 mucin peptide by Poly(d,l-lactic-co-glycolic acid) microspheres induces type 1 T helper immune responses.

Synthetic peptides corresponding to the variable tandem repeat domain of the cancer-associated antigen MUC1 mucin are candidates for cancer vaccines. In our investigation mice were immunized via subcutaneous injection with poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres containing a MUC1 mucin peptide. It was hypothesized that microencapsulation of the MUC1 mucin peptide would prime for antigen-specific Th1 responses while avoiding the need for traditional adjuvants and carrier proteins. Furthermore, an immunomodulator, monophosphoryl lipid A (MPLA), was incorporated into the peptide-loaded PLGA microspheres based on its ability to enhance Th1 responses. The results revealed T cell specific immune responses. The cytokine secretion profiles of the T cells consisted of high levels of interferon-gamma with undetectable levels of interleukin-4 and interleukin-10. Moreover, incorporation of MPLA in the MUC1 peptide-loaded PLGA microspheres resulted in an increase in interferon-gamma production. The antibody response was negative for IgM and IgG in the absence of MPLA; however, in the presence of MPLA antibody production was negative for IgM with a minimal IgG response consisting of IgG2a, IgG2b, and IgG3. Based on the antibody and cytokine profiles, it was concluded that MUC1 mucin peptide-loaded PLGA microspheres are capable of eliciting specific Th1 responses, which may be enhanced through the use of MPLA.

Ovalbumin peptide encapsulated in poly(d,l lactic-co-glycolic acid) microspheres is capable of inducing a T helper type 1 immune response.

An ovalbumin (OVA) peptide, consisting of residues 323-339, was incorporated into poly(d,l lactic-co-glycolic acid) (PLGA) microspheres and administered to mice. It was hypothesized that microencapsulation of the peptide in PLGA microspheres would avoid the need for traditional adjuvants and bias the immune response towards a type 1 T helper (Th1) response. An immunomodulator, monophosphoryl lipid A (MPLA), was incorporated into the microspheres to determine its efficacy in enhancing a Th1 response. The specificity of the immune response was determined using a T cell proliferation assay. The type of T helper response was determined by analysis of the cytokine secretion profiles of the proliferating T cells. Following s.c. immunization, the results revealed a T cell-specific immune response for the encapsulated OVA peptide both with and without MPLA. The cytokine profiles revealed high levels of IFN-gamma with very low levels of IL-4 and IL-10, suggesting a Th1 response. Furthermore, incorporation of MPLA in the peptide loaded PLGA microspheres resulted in an increase in the production of IFN-gamma. Hence, peptide-loaded PLGA microspheres are capable of eliciting a specific Th1 immune response, which may be further enhanced in the presence MPLA.

Differentiated thyroid cancer: determinants of disease progression in patients <21 years of age at diagnosis: a report from the Surgical Discipline Committee of the Children's Cancer Group.

OBJECTIVE: This study was done to define the extent of disease and evaluate the effect of staging and treatment variables on progression-free survival in patients with differentiated thyroid carcinoma who were less than 21 years of age at diagnosis. SUMMARY BACKGROUND DATA: Differentiated thyroid cancer in young patients is associated with early regional lymph node involvement and distant parenchymal metastases. Despite this, the overall long-term survival rate is greater than 90%, which suggests that biologic rather than treatment factors have a greater effect on outcome. METHODS: Variables analyzed for their impact on progression-free survival in a multi-institutional cohort of 329 patients included age, antecedent thyroid irradiation, extrathyroidal tumor extension, size, nodal involvement, distant metastases, technique of thyroid surgery and lymphatic dissection, initial treatment with 131Iodine, residual cervical disease, and histopathologic subtype. Surgical complications were correlated with the specific procedures completed on the thyroid gland or cervical lymphatics. RESULTS: The overall progression-free survival rate was 67% (95%, CI: 61%-73%) at 10 years with 2 disease-related deaths. Regional lymph node and distant metastases were present in 74% and 25% of patients, respectively. Progression-free survival was less in younger patients (p = 0.009) and those with residual cervical disease after thyroid surgery (p = 0.001). Permanent hypocalcemia was more frequent after total or subtotal thyroidectomy (p = 0.001) while wound complications increased after radical neck dissections (p < 0.00001). CONCLUSIONS: The progression-free survival rate was better after a complete resection and in older patients. Progression-free survival rate was the same after lobectomy or more extensive thyroid procedures, but comparison was confounded by the increased use of total or subtotal thyroidectomy in patients with advanced disease. The risk of permanent hypocalcemia increased when total or subtotal thyroidectomy was done. Thyroid lobectomy alone may be appropriate for patients with small localized lesions while total or subtotal thyroidectomy should be considered for more extensive tumors.

The management of choledocholithiasis in children in the era of laparoscopic cholecystectomy.

Although laparoscopic cholecystectomy has become the procedure of choice for gallbladder removal in children, the treatment of children who have choledocholithiasis remains unclear. For adults who have suspected choledocholithiasis, preoperative endoscopic retrograde cholangiopancreatography (ERCP) is a well-described and effective approach, however, its use for common bile duct stones in children has not been defined. The authors reviewed the records of 131 consecutive children undergoing laparoscopic cholecystectomy on two surgical services to define the efficacy of ERCP followed by laparoscopic cholecystectomy in managing choledocholithiasis in children. Fourteen children were suspected of having common duct stones noted on preoperative ultrasound scan and laboratory data. At ERCP, six children had no stones visualized; eight had stones and underwent stone extraction and sphincter dilation or sphincterotomy. All 14 underwent laparoscopic cholecystectomy a mean of 3.8 days after ERCP. None of the 14 had evidence of retained stones. Only one of 117 children undergoing primary laparoscopic cholecystectomy had unsuspected common bile duct stones and was treated with laparoscopic common bile duct exploration and stone removal. A management plan incorporating ERCP followed by early laparoscopic cholecystectomy is a safe and effective strategy for children who have choledocholithiasis.

Hepatic tumors in children.

Although there is broad consensus that complete resection is the cornerstone of successful management of hepatic malignancies in children, the optimal timing and integration of surgery and chemotherapy remain controversial. Excellent cure rates have been achieved with complete resection followed by multiagent chemotherapy for hepatoblastoma. Future studies are directed toward the identification of "poor risk" patients with protocols designed to improve survival for children with advanced disease and with hepatocellular carcinoma. A multidisciplinary team approach to the care of children with hepatic malignancies using the latest guidelines from clinical trials offers the best opportunity for successful outcomes.

Video-assisted thoracic surgery (VATS) for children with pulmonary metastases from osteosarcoma.

BACKGROUND: Video-assisted thoracic surgery (VATS) may complement open thoracotomy in children with osteosarcoma requiring pulmonary metastasectomy. METHODS: The records of children with metastatic pulmonary osteosarcoma considered for initial VATS intervention (n = 9) were reviewed. RESULTS: Two children did not have VATS exploration: one child with multiple bilateral nodules and another child with a deep parenchymal nodule. VATS provided diagnostic biopsy material in all cases when used (n = 7). Two children had benign inflammatory lesions; four children had VATS-directed wedge resections of solitary malignant lesions; and one child had VATS biopsy of diffuse parenchymal and pleural pulmonary disease not amenable to resection. The mean operative time and hospital length of stay were 1.78 +/- 0.54 h and 3.5 +/- 1.8 days, respectively. There were two complications of VATS: bleeding in a child, requiring a transfusion, and a latent pneumothorax in a patient after removal of the chest tube. CONCLUSION: VATS is safe, serves as an excellent diagnostic modality, complements the open thoracotomy, and may enable the surgeon to avoid more extensive procedures in selected cases.

Seeding of vascular grafts with genetically modified endothelial cells. Secretion of recombinant TPA results in decreased seeded cell retention in vitro and in vivo.

BACKGROUND: Seeding of small-diameter vascular grafts with endothelial cells (ECs) genetically engineered to secrete fibrinolytic or antithrombotic proteins offers the potential to improve graft patency rates. METHODS AND RESULTS: Sheep venous ECs were transduced with a retroviral vector encoding human tissue plasminogen activator (TPA). The ECs were seeded onto 4-mm-ID synthetic (Dacron) grafts. Retention of the seeded ECs was measured 2 hours after placement of the seeded grafts both in vitro in a nonpulsatile flow system and in vivo (in sheep) as femoral and carotid interposition grafts. On exposure to flow in vitro, ECs transduced with TPA were retained at a significantly lower rate (median, 67%) than either untransduced ECs (81%) or ECs transduced with a control retroviral vector producing beta-galactosidase (beta-Gal) (80%) (P < .05 for TPA versus either control). On implantation in vivo, ECs transduced with TPA were retained at a very low rate (median, 0%), significantly less than the retention of ECs transduced with the beta-Gal vector (32%; P < .00001). Decreased in vivo retention of ECs transduced with TPA correlated modestly with increased in vitro cellular passage level (r2 = .48; P < .0001) but not with in vivo blood flow rate (P = .45). Addition of the protease inhibitor aprotinin to the cell culture and graft perfusion media resulted in a significant (P < .05) increase in in vitro retention of ECs transduced with TPA. CONCLUSIONS: Increased TPA expression significantly decreases seeded EC adherence in vitro and in vivo. Gene therapy strategies for decreasing graft thrombosis may require expression of antithrombotic molecules that lack proteolytic activity.

Ultrasonography as an adjunct in the diagnosis of acute appendicitis: a 4-year experience.

This study was designed to evaluate the sensitivity and specificity of abdominal ultrasonography as a diagnostic modality in a large series of children who presented with possible appendicitis. From August 1990 to July 1994, 452 children (203 boys, 249 girls) with an average age of 11 years (range, 1 to 20 years) underwent graded compression ultrasonography of the right lower quadrant of the abdomen for the evaluation of possible appendicitis. In the first 18 months of the study all patients with the possible diagnosis of appendicitis (group I; 180 patients) had abdominal ultrasonography after members of the surgical team evaluated and documented their findings in the medical record. In the second study period (30 months), abdominal ultrasonography was recommended only when the clinical diagnosis of acute appendicitis was equivocal (group II; 272 patients). Abdominal ultrasonography was performed using the graded compression technique with a 5.0-MHz linear array transducer. A positive ultrasound study for appendicitis was defined as the presence of an enlarged noncompressible appendix with an outer wall to outer wall diameter of greater than 6 mm, the presence of a complex mass, or the presence of an appendicolith. The sonographic data were correlated with surgical and pathological findings. Appendicitis was confirmed in 112 of the 452 cases. In 17 of these, the appendix was perforated. In the overall group of 452 children, abdominal ultrasonography had a sensitivity of 90%, specificity of 96%, and accuracy of 95%. There was no significant morbidity in the 11 patients with a false-negative study result. All 11 patients had an uncomplicated appendectomy. There were 11 false-positive results; 10 of these patients had a negative laparotomy result (negative laparatomy rate, 8.9%). For the two groups, the sensitivity and specificity of ultrasonography in the diagnosis of appendicitis were equivalent (group 1: 88% sensitivity, 96% specificity; group 2: 92% sensitivity, 97% specificity). On the basis of the high sensitivity and specificity rates, ultrasonography of the appendix can be a useful adjunct to standard examination in the diagnosis of acute appendicitis.

Adenovirus-mediated gene transfer into normal rabbit arteries results in prolonged vascular cell activation, inflammation, and neointimal hyperplasia.

Adenovirus vectors are capable of high efficiency in vivo arterial gene transfer, and are currently in use as therapeutic agents in animal models of vascular disease. However, despite substantial data on the ability of viruses to cause vascular inflammation and proliferation, and the presence in current adenovirus vectors of viral open reading frames that are translated in vivo, no study has examined the effect of adenovirus vectors alone on the arterial phenotype. In a rabbit model of gene transfer into a normal artery, we examined potential vascular cell activation, inflammation, and neointimal proliferation resulting from exposure to replication-defective adenovirus. Exposure of normal arteries to adenovirus vectors resulted in: (a) pronounced infiltration of T cells throughout the artery wall; (b) upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in arterial smooth muscle cells; (c) neointimal hyperplasia. These findings were present both 10 and 30 d after gene transfer, with no evidence of a decline in severity over time. Adenovirus vectors have pleiotropic effects on the arterial wall and cause significant pathology. Interpretation of experimental protocols that use adenovirus vectors to address either biological or therapeutic issues should take these observations into account. These observations should also prompt the design of more inert gene transfer vectors.