Small-animal PET of tumor angiogenesis using a (76)Br-labeled human recombinant antibody fragment to the ED-B domain of fibronectin.

The aim of this study was to image the extra domain B (ED-B) of fibronectin, an angiogenesis-related target, in solid tumors using small-animal PET. Toward this aim, an ED-B fibronectin-binding human antibody derivative (L19-SIP) was labeled with (76)Br via an enzymatic approach. Biodistribution and imaging studies were performed in human teratoma-bearing mice for up to 48 h after injection. METHODS: L19-SIP was labeled with (76)Br using bromoperoxidase/H(2)O(2). The stability of the labeled antibody was tested both in vitro and in vivo. Biodistribution and small-animal imaging studies (PET and CT) were performed in F9-bearing 129/sv mice (n = 3 or 4). RESULTS: The enzymatic radiobromination approach afforded the labeled antibody in high yield (>55%) under mild reaction conditions. (76)Br-L19-SIP stability in mouse serum proved to be similar to that of the (125)I-labeled analog (>80% of intact material at 48 h after injection). Fast and specific in vivo targeting was obtained in tumors and other organs expressing ED-B fibronectin (i.e., ovaries and uterus). However, slow renal clearance and persistent activity predominately in blood and stomach suggests partial (76)Br-L19-SIP debromination in vivo. This debromination was confirmed in a metabolism study in normal mice. The F9 tumors were clearly imaged by small-animal PET at each considered time point, starting at 5 h up to 48 h after injection. CONCLUSION: (76)Br-L19-SIP specifically accumulated at the target site, enabling detailed small-animal PET of tumor neovasculature. Therefore, targeting the angiogenesis-associated expression of ED-B fibronectin can be a valuable tool for tumor detection using molecular imaging with PET.     

The Hyperplantarflexion Ankle Fracture Variant

Various patterns of ankle fractures that are not accounted for by common classification systems have been the subject of case reports. The first difficulty with these variant patterns is recognizing all associated pathology, followed by the successful application of stable fixation. The purpose of this study was to describe the common morphologic features and ligamentous injuries of a unique variant fracture pattern, as well as the surgical treatment technique and the short-term functional and radiographic outcomes. Of 121 consecutive unstable ankle fractures over a 2-year period, 7 patients were found to have a similar constellation of injuries around the ankle. A vertical shear fracture of the posteromedial tibial rim was the main feature. Six of the 7 also had a fracture of the posterior malleolus. On magnetic resonance imaging, the deltoid and posterior tibiofibular ligaments were intact in all cases. Fractures were treated with open anatomic reduction of the posteromedial and posterior fragments with antiglide plate fixation. All fractures healed at 2 months without loss of reduction, fixation failure, or surgical complications. The average American Academy of Orthopaedic Surgeons lower extremity score was 79 at an average of 8 months' follow-up. The common radiographic and morphologic features associated with this posteromedial fracture indicate that it likely occurs through a common mechanism that involves hyperplantarflexion. The characteristics of this fracture pattern have not been fully described previously, but this ankle fracture variant may occur in up to 6% of cases. Unstable ankle fractures should be evaluated carefully for evidence of posteromedial involvement so appropriate treatment may proceed.     

D-cycloserine augmented exposure therapy for obsessive-compulsive disorder.

BACKGROUND: D-cycloserine (DCS), a glutamatergic partial N-methyl-d-aspartate (NMDA) agonist, can facilitate extinction learning related to cued fear in animals and humans. We predicted that DCS would accelerate obsession-related distress reduction in patients with obsessive-compulsive disorder (OCD) undergoing extinction-based exposure therapy. METHODS: We administered DCS (125 mg) or placebo in a double-blind fashion to individuals with OCD approximately 2 hours before each exposure session. RESULTS: D-cycloserine decreased both the number of exposure sessions required to achieve clinical milestones and the rate of therapy dropout. After four exposure sessions, patients in the DCS group reported significantly greater decreases in obsession-related distress compared with the placebo group; however, after additional sessions, the placebo group tended to catch up. CONCLUSIONS: D-cycloserine augmentation has the potential to increase the efficiency, palatability, and overall effectiveness of standard exposure therapy for OCD.     

Factor analysis of the Cohen-Mansfield Agitation Inventory in three large samples of nursing home patients with dementia and behavioral disturbance.

OBJECTIVE: Limited work has addressed the construct validity of the Cohen-Mansfield Agitation Inventory (CMAI) in nursing home patients. The authors tested the CMAI factor structure by use of data from three samples of nursing home patients categorized a priori as having at least mild behavioral and psychological symptoms of dementia. METHODS: CMAI data were from the baseline assessment of three randomized, placebo-controlled trials of risperidone for treating elderly nursing home patients. Exploratory factor analyses were conducted on two trials (N = 304; N = 344), and the results of these exploratory factor analyses were then tested with confirmatory factor analysis by use of data from a third trial (N = 617). RESULTS: Principal-components analysis suggested the presence of four factors: 1) Aggressive Behavior (hitting, kicking, scratching, biting, pushing, grabbing, throwing things, cursing or verbal aggression, spitting, tearing things/destroying property, hurting self or others, screaming); 2) Physically Non-Aggressive Behavior (pacing, trying to get to a different place, general restlessness, inappropriate dressing or disrobing, handling things inappropriately, performing repetitious mannerisms); 3) Verbally Agitated Behavior (complaining, constant requests for attention, repetitive questions, negativism); and 4) Hiding and Hoarding. Confirmatory factor analysis indicated that the four-factor solution was a reasonable fit to the data. CONCLUSION: Four factors emerged on the CMAI in nursing home patients with behavioral and psychological symptoms of dementia. The results obtained converge reasonably with previous publications concerning the factor structure of the CMAI, which, taken together, suggest a fairly robust factor structure for the instrument.     

Central serous chorioretinopathy and risk for obstructive sleep apnea

Patients with obstructive sleep apnea (OSA), in comparison to controls, have increased levels of circulating epinephrine and norepinephrine, both of which are risk factors for the development of central serous chorioretinopathy (CSCR). The aim of this pilot study was to investigate the frequency of symptoms that suggest OSA in CSCR patients and normal controls. The Berlin Questionnaire, a validated research tool to assess risk for OSA, was administered to 29 patients who met the criteria for active, acute, non-steroid-induced CSCR and 29 controls matched for age and sex. In this retrospective case-controlled study, the main outcome measure was increased risk for OSA. The mean age of the patients was 47.8 years (range 29–72) and the mean age of controls was 47.3 years (range 25–70). Seventy-six percent (22) of both groups were men. Survey scores showed 58.6% (17) of patients with CSCR to be at an increased risk for OSA compared to 31.0% (nine) of controls. A conditional logistic regression analysis showed that the CSCR group had a higher proportion with an increased risk for OSA compared to the control group (odds ratio=3.67; 95% CI: 1.02, 13.14; P = 0.046). Patients with CSCR may be more likely than other adults to have OSA, and screening for this sleep disorder should be considered in this population. Further research is warranted to determine whether sleep apnea may contribute to the development of CSCR, and to assess whether treatment of sleep apnea might offer a new therapeutic option for some patients with CSCR.     

Mapping the social and physical contexts of physical activity across adolescence using ecological momentary assessment

BACKGROUND: Research has sought to understand how environmental factors influence adolescent physical activity, yet little is known about where and with whom adolescents are physically active. PURPOSE: This study used electronic ecological momentary assessment (e.EMA) to map the social and physical contexts of exercise and walking across adolescence. Differences in physical activity contexts by gender, grade in school, day of the week, and season were examined. METHODS: Twice a year between 9th and 12th grade, 502 adolescents (51% female) of mixed ethnicity (55% White) participated in 4-day e.EMA intervals (Thursday-Sunday) where their primary activity (e.g., exercise, TV, homework), social company (e.g., friends, family, class), and physical location (e.g., home, school, outdoors) were assessed every 30 (+/-10) min during waking hours. RESULTS: Overall, greater proportions of exercise and walking were reported with friends, outdoors, and at school. However, boys were more likely to report exercising and walking in outdoor locations than girls. Exercising with classmates, family, and at school decreased across high school. Walking with family, friends, and outdoors also decreased. On weekdays compared to weekends, students reported a greater proportion of their exercise and walking at school. Students were more likely to report exercising and walking outdoors in the fall and the spring than in the winter. CONCLUSION: e.EMA showed that the social and physical contexts of adolescent exercise and walking vary as a function of gender, grade in school, day of the week, and season. Understanding the contexts of physical activity during the high school years can be helpful in designing interventions during adolescence.     

One-year follow-up results of combined use of CO<Subscript>2</Subscript> laser and cold instrumentation for Reinke’s edema surgery in professional voice users

The purpose of this study was to present our experience with combined use of CO₂ laser and cold instrumentation for Reinke’s edema surgery and to evaluate 1-year follow-up results of the technique in a series of professional voice users. Fifteen patients with Reinke’s edema who underwent microlaryngoscopic surgery were included. Videolaryngostroboscopy, perceptual and acoustic voice analyses were performed before and after surgery. During the 1-year follow-up, no recurrence of Reinke’s edema was encountered. Significant postoperative improvement was obtained in the quality of voice, in terms of GRBAS scores, Fo, jitter, shimmer and NHR. No evidence of laryngeal cancer was found on the histological examinations. Combined use of CO₂ laser and cold instrumentation provides a reliable and safe method for Reinke’s edema surgery, and cessation of smoking, voice rest and control of the laryngopharyngeal reflux contribute to the success of surgery. We consider that the removal of redundant mucosa of the vocal fold reduces the risk of the recurrence of Reinke’s edema and provides better quality of voice. However, it does not imply that our method is superior to others’, but this procedure constitutes an effective treatment of choice for Reinke’s edema patients, including professional voice users.     

Tibiotalocalcaneal arthrodesis with retrograde intramedullary nailing

Nineteen patients (20 feet) with severe hindfoot and ankle deformity underwent tibiotalocalcaneal fusion with a retrograde locked intramedullary nail as a limb-salvage procedure. The purpose of this study was to compare the complication rates of this procedure in diabetic versus nondiabetic patients. There were 8 men and 11 women with preoperative diagnoses including Charcot neuroarthropathy, primary osteoarthritis, rheumatoid arthritis, equinocavovarus, posttraumatic osteoarthritis, gouty arthritis, and ankle malunion. Ten of 20 procedures were performed in patients with diabetes. The average patient age was 56 years, and the average postoperative follow-up was 19.8 months. Nineteen of 20 ankles (95%) achieved successful fusion with an average time of 4.1 months. Four patients (21%) required either a fracture brace or an ankle foot orthosis at final follow-up. Five patients (25%) had major complications and 11 patients had minor complications. Major complications included osteomyelitis (n = 2), Charcot arthropathy (n = 2), failure of fixation (n =1), soft-tissue necrosis (n = 1), cardiac arrest (n = 1), cerebral vascular accident (n = 1), and fatal pulmonary embolus (n = 1). All patients with major complications were diabetic, and 14 of 20 combined major and minor complications occurred in patients with diabetes. The complication rate was found to be high in diabetic patients with end-stage deformity undergoing a limb salvage