Therapeutic deep brain stimulation disrupts movement-related subthalamic nucleus activity in parkinsonian mice.

Subthalamic nucleus deep brain stimulation (STN DBS) relieves many motor symptoms of Parkinson's disease (PD), but its underlying therapeutic mechanisms remain unclear. Since its advent, three major theories have been proposed: (1) DBS inhibits the STN and basal ganglia output; (2) DBS antidromically activates motor cortex; and (3) DBS disrupts firing dynamics within the STN. Previously, stimulation-related electrical artifacts limited mechanistic investigations using electrophysiology. We used electrical artifact-free GCaMP fiber photometry to investigate activity in basal ganglia nuclei during STN DBS in parkinsonian mice. To test whether the observed changes in activity were sufficient to relieve motor symptoms, we then combined electrophysiological recording with targeted optical DBS protocols. Our findings suggest that STN DBS exerts its therapeutic effect through the disruption of movement-related STN activity, rather than inhibition or antidromic activation. These results provide insight into optimizing PD treatments and establish an approach for investigating DBS in other neuropsychiatric conditions.

Timing of colonoscopy after resection for colorectal cancer: are we looking too soon?

BACKGROUND: Based on current National Comprehensive Cancer Network guidelines, colonoscopic surveillance after colorectal cancer resection should begin at 1 year. OBJECTIVE: The aim of this study was to determine whether the incidence of cancer or advanced polyp detection rate was high enough to justify colonoscopy at 1 year. DESIGN: The Ochsner Clinic Tumor Registry Database was queried for patients who underwent a segmental colectomy or proctectomy between 2002 and 2010. Patients who had a preoperative colonoscopy and at least 1 documented postoperative colonoscopy were included. We considered new cancer or polyps of ≥1 cm as missed on the preoperative colonoscopy. Patients with an identified genetic trait causing a predisposition to colorectal cancer were excluded. RESULTS: Five hundred twelve patients underwent resection, and 155 met our inclusion criteria. The average age was 64 years, and 53% patients were male. There were 32.9% with stage I disease, 35% with stage II disease, 27.1% with stage III disease, and 5.2% with stage IV disease. Of these patients, 52.2% had a right colectomy, 7.1% had a left colectomy, 16.8% had a sigmoid colectomy, 22% had a low anterior resection, and 1.3% had a transanal resection. The average time to first postoperative colonoscopy was 478 days (SD ±283 days). Twenty-four patients had adenomatous polyps detected on their first surveillance colonoscopy, but only 5 (3.2%) polyps were ≥1 cm, and there was no correlation between stage of cancer and finding a polyp. No new cancers were detected, but 3 (1.9%) had an anastomotic recurrence. CONCLUSIONS: The performance of surveillance colonoscopy at 1 year resulted in the detection of only 5 missed polyps ≥1 cm and no metachronous cancers. Anastomotic recurrences were rare, and the majority were in patients who had rectal cancer that could be evaluated by in-office flexible sigmoidoscopy. Extending the time to first colonoscopy appears to be safe and would help conserve valuable resources, including physician and facility time, which is imperative in the current health care climate.

Influence of complications and extent of weight loss on quality of life after laparoscopic Roux-en-Y gastric bypass.

INTRODUCTION: Obesity decreases health-related quality of life, but bariatric surgery improves it. This study evaluates the effect of laparoscopic Roux-en-Y gastric bypass, postoperative complications, and percentage of excess body weight loss on quality of life. METHODS: SF-36v.1 questionnaires were administered preoperative (n = 505), 1 year (n = 237) and 2 years (n = 106) following laparoscopic Roux-en-Y gastric bypass. Analysis was performed using Student's t-test and multiple logistic regression analysis. Complications were defined as requiring additional intervention or hospitalization. SF-36 responses were normalized to 1998 US norms. RESULTS: Bariatric patients scored significantly lower on all scales compared to the normal population. Health-related quality of life notably improves after surgery. At 1 year, scores not only improved from baseline, but were higher than those of the non-obese reference population regardless of complications. Compared to patients at 2 years without complications, patients experiencing complications reported decreased scores, but scores remained higher than preoperative scores in five scales. At 1 and 2 years, < or = 50% excess body weight loss decreased scores; however, scores were significantly improved from baseline. CONCLUSIONS: Health-related quality of life in bariatric patients is worse than in controls, but it improves 1 and 2 years after laparoscopic Roux-en-Y gastric bypass. Complications or < or = 50% excess body weight loss slightly decreases this improvement.

Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness.

AgRP is a neuropeptide that stimulates food intake through inhibition of central melanocortin receptors (MCRs). In humans, the non-conservative amino acid substitution Alanine (Ala) 67 Threonine (Thr) has been associated with Anorexia Nervosa and with leanness. In the present study, the cellular distribution, processing and in vitro and in vivo activities of Ala67 and Thr67 AgRP were investigated. Western blots of media and lysates of BHK cells stably transfected with Ala67 or Thr67 expression constructs showed identical AgRP bands. Both Ala67 and Thr67 AgRP colocalised with the Golgi apparatus, but not with the ER or lysosomes when expressed in Att20 D16V cells. Also, no differences were observed between the potencies of bacterially expressed Ala67 and Thr67 AgRP to stimulate MC4R in a reporter gene assay or inhibit food intake in rats. Taken together, no evidence was found for a functional defect of Thr67 AgRP related to MC4R interactions.

Poor cell surface expression of human melanocortin-4 receptor mutations associated with obesity.

The melanocortin-4 receptor (MC4R) plays an important role in the regulation of body weight in rodents. Mutations in the coding region of the MC4R are found more frequently in obese individuals, supporting the hypothesis that also in humans deficient melanocortin signaling may lead to obesity. Family studies that were carried out to demonstrate the relevance of single mutations for obesity were mostly inconclusive, most likely due to small sample size and complexity of the trait. In addition, the existing pharmacological data of the mutant receptors are limited in that for most mutations the effect on receptor expression level and Agouti-related protein (AgRP) pharmacology have not been studied. The aim of the present study was to gain further insight into the impact of the MC4R mutations on receptor function. Eleven missense mutations were tested for cell surface expression, affinity for alpha-melanocyte-stimulating hormone (alpha-MSH) and AgRP-(83-132), and the biological response to alpha-MSH. All mutants were poorly expressed at the cell surface, as measured by 125I-[Nle4-D-Phe7]alpha-MSH binding, and only a few mutants showed altered pharmacology for alpha-MSH and AgRP. Hemagglutinin-tagged mutant receptors were retained in the intracellular environment. These pharmacological data provide a basis to estimate the quantitative effect of MC4R mutations for the development of obesity.

An open-label, dose-ranging study of atomoxetine in children with attention deficit hyperactivity disorder.

OBJECTIVE: The goal of this study was to evaluate the tolerability and effectiveness of the experimental, noradrenergic specific reuptake inhibitor atomoxetine in the treatment of children with attention deficit hyperactivity disorder (ADHD). METHODS: This was an open, prospective, dose-ranging study of atomoxetine monotherapy in the treatment of 30 children with ADHD between the ages of 7 and 14 years. Atomoxetine was started at 10-20 mg/day and titrated weekly up to 90 mg over 11 weeks, depending on response and adverse effects. Twenty-two children completed the full 11 weeks. We assessed efficacy with weekly clinician and parent ratings of ADHD and oppositional symptoms and monitored adverse effects, laboratory findings, and cardiovascular parameters. RESULTS: Treatment with atomoxetine (mean final, total daily dose of 1.9 mg/kg/day) was very well tolerated without meaningful adverse effects. Atomoxetine significantly reduced core symptoms of ADHD (ADHD-Rating Scale-IV; 38.6% decrease vs. baseline, p < 0.001) with significant improvement (p < 0.05) in all but 1 of the 18 individual items in the ADHD-Rating Scale-IV. More than 75% of subjects who completed 10 weeks of treatment showed > 25% decrease in ADHD symptoms. CONCLUSIONS: These findings extend to children the positive results previously reported in adults diagnosed with ADHD who were treated with atomoxetine. These results support additional controlled trials of atomoxetine in cases of pediatric ADHD.

Results of a randomized, prospective, multicenter trial of mycophenolate mofetil versus azathioprine in the prevention of acute lung allograft rejection.

BACKGROUND: Although the use of mycophenolate mofetil (MMF) has reduced the incidence of acute rejection in heart and kidney allograft recipients, its role in lung transplantation remains controversial. Therefore, we conducted a randomized, prospective, open-label, multicenter study in lung transplant recipients to determine whether MMF decreases episodes of acute allograft rejection when compared with azathioprine (AZA). METHODS: Between March of 1997 and January of 1999, 81 consecutive lung transplant recipients from two centers were prospectively randomized to receive cyclosporine, corticosteroids, and either 2 mg/kg per day of AZA or 1 g twice daily of MMF. The primary study endpoint was biopsy-proven acute allograft rejection over the first 6 months posttransplant. Secondary endpoints included clinical rejection, cytomegalovirus (CMV) infection, adverse events, and survival. Surveillance bronchoscopies were performed at 1, 3, and 6 months, or if clinically indicated. Pathologists interpreting the biopsy results were blinded to the randomization. Results were analyzed according to intention-to-treat. Between group comparisons of means and proportions were made by using two sample t tests and Fisher's exact tests, respectively. Six-month survival was calculated by the Kaplan-Meier method and compared by the log rank test. RESULTS: Thirty-eight patients were prospectively randomized to receive AZA, and 43 MMF. The incidence of biopsy proven grade II or greater acute allograft rejection at 6 months was 58% in the AZA group and 63% in the MMF group (P=0.82). The 6-month survival rates in the MMF and AZA groups were 86% and 82%, respectively (P=0.57). Rates of CMV infection and adverse events were not significantly different between the two groups. CONCLUSIONS: Acute rejection rates and overall survival at 6 months are similar in lung transplant recipients treated with either MMF- or AZA-based immunosuppression.

Development of a phantom for morphometric X-ray absorptiometry.

Morphometric X-ray absorptiometry (MXA) has recently been developed to assess vertebral deformity status using dual energy X-ray absorptiometry (DXA) machines. In contrast to bone densitometry, a vertebral morphometry phantom is not supplied by any machine manufacturer. The aim of this study was to develop a suitable phantom to quantify the accuracy and precision of the vertebral measurement software on three DXA scanners in vitro and to perform a weekly quality control (QC) scan over a 30-month period to evaluate any drift or changes in measurement accuracy over time. The phantom was constructed from Perspex and aluminium to simulate soft tissue and bone, respectively. 13 aluminium rectangles (each 30 mm wide, 25 mm high and 3 mm thick, with edges ("endplates") 6 mm thick) were set into one side of a solid Perspex block to represent the vertebral bodies from the fourth thoracic (T4) to the fourth lumbar (L4). The phantom was scanned on both the Hologic QDR2000plus and the QDR-4500A as well as the Lunar Expert-XL. Three consecutive lateral MXA scans were acquired on the Hologic machines using each of the scan modes available. On the QDR-2000plus, the lateral scan modes available are fast, array and high definition, which are all dual energy modes. These three scan modes are also available on the QDR-4500A, with the addition of a single energy scan mode. Four lateral scans were acquired on the Expert-XL machine using the single scan mode available. Each MXA scan was analysed twice by a trained operator using the standard software supplied by each manufacturer. A QC scan was performed approximately weekly over a 30-month period on only the QDR-4500A machine, and total phantom height was measured from the inferior edge of L4 to the superior edge of T4. Accuracy of "vertebral" height measurement varied between the three DXA machines and between the scan modes available. All underestimated "true" vertebral height by between 0.4% and 8.6%, with the scan modes using finer collimation producing the most accurate results. Repeat analysis precision of vertebral height measurement was best on the QDR-4500A, followed by the Expert-XL, and was poorest on the QDR-2000plus. The QC scans acquired on the QDR-4500A suggested that it was a highly stable machine, little affected by even major repairs. It must be remembered that these in vitro phantom results may not be representative of the true in vivo situation. The MXA phantom appears to be a useful tool for documenting the stability of the mechanical instruments and for checking the long-term consistency of operator precision.

Vertebral morphometry: a comparison of long-term precision of morphometric X-ray absorptiometry and morphometric radiography in normal and osteoporotic subjects.

Vertebral morphometry, the quantification of vertebral body shape, has proved a useful tool in the identification and evaluation of osteoporotic vertebral deformities in both epidemiologic surveys and clinical trials. Although conventionally it has been performed on lateral radiographs of the thoracolumbar spine (morphometric radiography, MRX), it may now be accomplished on morphometric X-ray absorptiometry (MXA) scans, acquired on dual-energy X-ray absorptiometry (DXA) machines. In this study the long-term precision of vertebral height measurement using MXA and MRX was directly compared. Initially 24 postmenopausal women were recruited (mean age 67+/-5.8 years): 12 normal subjects (group 1) and 12 with osteoporosis and known vertebral deformities (group 2). Each subject attended for a baseline visit at which they had a MXA examination and lateral thoracic and lumbar radiographs. Twenty-one subjects then returned 1.7+/-0.4 years later (10 subjects from group 1 and 11 from group 2) for a follow-up visit to repeat both the MXA scans and conventional radiographs. The baseline MXA scans and conventional radiographs were each analyzed quantitatively by two observers in a masked fashion, using a standard six-point method. The follow-up images were then analyzed by the same observers. The MRX observers were masked to the baseline analyses, while the MXA observers utilized the manufacturer's 'compare' facility. On all scans and radiographs anterior (Ha), mid (Hm) and posterior (Hp) vertebral heights were measured and wedge (Ha/Hp) and mid-wedge (Hm/Hp) ratios calculated for each vertebral body, ideally from T4 to L4. MRX analyzed 129 of the 130 available vertebrae in group 1 at both visits and 141 of the 143 available in group 2, while MXA analyzed 124 vertebrae in group 1 at both visits and 127 in group 2. Intra- and inter-observer precision errors, particularly in terms of coefficient of variation (CV%), were larger for MXA than for MRX in both normal subjects and those with vertebral deformities. For example, intra-observer precision errors for vertebral height measurement were 0.62 mm (2.9%) for MXA compared with 0.63 mm (2.2%) for MRX in group 1 (normal) subjects and 0.82 mm (4.2%) for MXA compared with 0.85 mm (3.3%) for MRX for group 2 (osteoporosis and vertebral deformities) subjects. Both MXA and MRX inter-observer precision was clearly poorer than the intra-observer precision, a problem associated with any morphometric technique. This was particularly noticeable for MXA; for example, precision of vertebral height measurement in group 1 subjects was 0.62 mm (2.9%) for intra-observer compared with 0.99 mm (4.6%) for inter-observer analyses. MXA and MRX intra- and inter-observer precision was significantly poorer for subjects with vertebral deformities compared with those without, with the CV% for subjects with vertebral deformity approximately 50% greater than that of normal subjects. For example, MRX intra-observer precision for the midwedge ratio was 2.6% for group 1 subjects compared with 3.8% for group 2 subjects. The precision of vertebral height measurement on deformed vertebrae of group 2 subjects was poorer than that for normal vertebrae in the same subjects using both MXA and MRX, as a result of increased variability in point placement. For example, MXA intra-observer precision (RMS SD) for the wedge ratio precision was 0.037 (3.9%) for normal vertebrae compared with 0.060 (6.6%) for deformed vertebrae. We conclude that MXA precision was generally poorer than MRX, although both techniques were adversely affected by the presence of vertebral deformities and the use of more than one observer. Although precision errors for both techniques were substantially smaller than the 20-25% reduction in vertebral height frequently proposed to identify incident deformities, the poorer precision of MXA may lead to an increased risk of erroneous classification of vertebrae as normal or deformed.

Visual assessment of vertebral deformity by X-ray absorptiometry: a highly predictive method to exclude vertebral deformity.

The accurate identification of prevalent vertebral fractures is important in both the clinical and research setting as they are associated with increased risk of further fracture and irreversible clinical consequences. This study reports a direct comparison of prevalent vertebral deformity identification using X-ray absorptiometry (XA) scans, acquired on a dual-energy X-ray absorptiometry (DXA) machine, and conventional radiographs in a diverse group of 161 postmenopausal women, ranging from healthy subjects with normal bone mineral density (BMD) to osteoporotic subjects with multiple vertebral deformities. Deformities were identified by a trained operator by visual assessment of the XA scans (VXA) and semiquantitatively by an experienced radiologist on the conventional radiographs (XSQ). Subjects were recruited prospectively and were triaged according to their VXA results into normal, equivocal and definite deformity groups. VXA and XSQ demonstrated good agreement (96.3%, K = 0.79) in classifying vertebrae as normal or deformed in the 1978 of 2093 vertebrae deemed analyzable on both the XA scans and conventional radiographs. VXA showed good sensitivity (91.9%) in the identification of moderate/severe XSQ deformities and an excellent negative predictive value (98.0%) was produced when VXA was used to distinguish subjects without vertebral deformities from those with possible or definite deformities on a per subject basis. The majority of disagreement between the two methods resulted from different classification of mild wedge and endplate deformities and the poor visualization of upper thoracic vertebrae on the XA scans. Agreement improved, particularly on a per subject basis, when analysis was restricted to the vertebral levels from L4 to T7. Visual triage of XA scans by a trained operator would seem to be swift, convenient and cost-effective method, with excellent negative predictive value, to distinguish subjects with very low risk of vertebral deformities from those with possible deformities. These 'normal' subjects can then be excluded prior to performing conventional radiographs and further time-consuming and costly methods of vertebral deformity assessment such as XSQ by an experienced radiologist and/or quantitative morphometry. VXA may prove useful in the clinical evaluation of patients at risk of osteoporosis as an adjunct to BMD scans or in the selection of subjects for osteoporosis-related clinical trials.

Vertebral morphometry: repeat scan precision using the Lunar Expert-XL and the Hologic 4500A. A study for the 'WISDOM' RCT of hormone replacement therapy.

On radiation safety grounds there is concern about the morbidity attributable to routine radiographs of the spine for the identification of new fractures in large-scale trials of fracture prevention. However, the role of the potentially safer low-radiation-dose technique of vertebral morphometry performed by third generation dual-energy X-ray absorptiometry equipment requires evaluation for use in clinical trials. We have therefore investigated the short-term inter-scan imprecision as well as the imprecision attributable to different-day analyses by the same operator and differences in analyses by different operators. The volunteer subjects were participants in a pilot study for a randomized controlled trial of hormone replacement therapy (Women's International Study of long Duration Oestrogen after Menopause, WISDOM). Each subject had two morphometric X-ray analysis scans separated by 2-4 weeks. Exclusions were women with densitometrically defined osteoporosis, as defined by the WHO criterion, and women with a body mass index exceeding 30.9 kg/m2. On average, the women were 58.7 years of age and had bone mineral density values in the lumbar spine which were about 0.7 SD units higher than a reference US female age-matched population. Scans were assessed from vertebrae T7 through L4. In the study there were no clinically significant differences in performance between the Hologic QDR 4500A and the Lunar Expert XL equipment. Between-scan imprecision was significantly worse than imprecision attributable to reanalysis of the same scan by a different operator or the same operator after an interval. Vertebral level had an effect on measurement uncertainty, especially at the level of the diaphragm and at T7. Coefficients of variation, expressed as percentages of mean values, were better for absolute height measurements than for height ratios, ranging from 1.75% to 3.40% for the three heights measured on three separate machines and from 2.34% to 4.11% for the two height ratios. These results compared favorably with the equivalent figures from a parallel study of morphometry precision undertaken using standard lateral radiographs of the thoracic and lumbar spine (3.1-3.6% and 3.8-3.9%, respectively). We conclude that in trials of prevention therapy in women (or men) selected for not having osteoporosis, low-dose vertebral morphometry using the Hologic 4500A, the Lunar Expert XL or similar equipment is preferable on safety grounds to the classical technique based on standard radiographs, although conventional radiology may still be required in those with prevalent or incident deformities to exclude causes other than osteoporosis. The place of this low-dose technique in trials performed on patients with osteoporosis requires further study.

Partial parotidectomies: morbidity and benign tumor recurrence rates in a series of 94 cases.

OBJECTIVES: Review the methods available for parotidectomy. Describe the technique of partial parotidectomy assisted by evoked electromyographic nerve location and the expected morbidity and benign and low-grade cancer tumor recurrence rates from this modified procedure. STUDY DESIGN: From 1983 to 1999 the author performed or assisted in 94 parotidectomies (79 partial), all done by a single specialty group and all using evoked electromyographic nerve location. The cases were surveyed by reviewing all the hospital and office records on these cases and tabulating the type and extent of surgery, pathology, postoperative problems recorded, and long-term follow-up. METHODS: Partial parotidectomy was elected in those cases of benign and low-grade malignant disease in which adequate tumor removal required a less than complete lobectomy or total parotidectomy. Heavy reliance was placed on proactive nerve location by an evoked electromyographic device with dissecting/stimulating hemostat. A retrospective review focusing on these cases was performed based on the patient charts and their continued documentation by the practice. RESULTS: In 79 partial parotidectomies there were no documented facial nerve injuries and one incidence of recurrence of a benign mixed tumor and an acinic cell carcinoma, respectively. CONCLUSION: Partial parotidectomy has the advantages of reduced risk to the facial nerve, reduced operating time, possible outpatient surgery, and no apparent risk of increased recurrence of benign tumors.

Morphometric X-ray absorptiometry and morphometric radiography of the spine: a comparison of prevalent vertebral deformity identification.

Prevalent vertebral deformities are associated with a substantially increased risk of subsequent vertebral and nonvertebral fractures. Knowledge of vertebral fracture status is an important component in the prediction of further fractures in patients with osteoporosis. This study reports a comparison of the quantitative identification of vertebral deformities on morphometric X-ray absorptiometry (MXA) scans and conventional radiographs (MRX) in 161 postmenopausal women (mean age +/- SD, 64 +/- 7.1 years) recruited from patients referred by their family doctor for bone density measurement (n = 119) and osteoporotic subjects with known vertebral deformities attending an osteoporosis clinic (n = 42). Each subject had MXA scans and MRXs of the thoracolumbar spine, to image the vertebrae from T4-L4, at a single visit. The scans and radiographs were analyzed by two trained observers using six points to quantify the shape of each vertebral body. From these points, three vertebral heights were measured: anterior, middle, and posterior. Vertebral deformities were identified using the algorithms proposed by Eastell and by McCloskey. Generally good to excellent agreement (per vertebra, kappa = 0.87-0.93; per subject, kappa = 0.81-0.91) was observed between the two algorithms used for quantitative vertebral deformity identification using MXA or MRX. More moderate agreement (per vertebra, kappa = 0.70-0.79; per subject, kappa = 0.67-0.75) was seen when comparing the same algorithm between MXA and MRX. Agreement between MXA and MRX for the McCloskey algorithm was better than for the Eastell algorithm, largely because of the lower number of false positives produced by the McCloskey methodology. Deformity identification by MXA was limited because of poor image quality, primarily in the upper thoracic spine. One in six MRX deformities were missed by MXA as they occurred in vertebrae not visualized sufficiently for analysis on the MXA scans. Deformity identification was poorer in the upper thoracic spine in analyzable vertebrae with a sensitivity of 50.0% for MXA in terms of MRX using the Eastell algorithm for the vertebral levels T4-T7, compared with 80.6% for L1-L4A. MXA proved to be more effective at identifying moderate to severe MRX deformities producing a sensitivity of 22.0% for MXA in terms of identifying MRX grade 1 deformities using the Eastell algorithm, compared with 81.6% for grade 2 deformities. Although MXA image quality is inferior to that of conventional radiographs, MXA has distinct advantages such as a substantially reduced effective dose to the patient and acquisition of a single image of the spine. MXA is a potentially useful, relatively fast, low-radiation technique to identify prevalent vertebral deformities, particularly moderate to severe deformities in the middle/lower thoracic and lumbar spine, in conjunction with morphometric radiography in some patients.

Anastomotic infections in lung transplant recipients.

OBJECTIVES: Anastomotic infections are an uncommon but potentially devastating complication after lung transplantation. The incidence, microbiology, predisposing factors, and clinical outcomes of anastomotic infections have not been well described. METHODS: We performed a retrospective chart review of the first 283 lung or heart-lung transplant recipients performed at Duke University Medical Center and identified all cases of anastomotic infection. RESULTS: Fifteen patients (5.3%) developed anastomotic infections. Aspergillus caused infection in six patients, Candida in eight patients and Staphylococcus aureus in one patient. Bilateral or right lung transplantation and the use of induction immunosuppression with monoclonoal or polyclonal antibodies are associated with a higher incidence of anastomotic infections. All patients with fungal anastomotic infections were treated with a combination of systemic and inhaled antifungal agents. All patients had improvement of their anastomotic sites after treatment and no patients developed anastomotic dehiscence. CONCLUSIONS: Anastomotic infection is an infrequent complication after lung transplantation, and is caused predominately by fungal pathogens. In contrast to previous reports, anastomotic dehiscence did not occur in any patient in our series. Treatment with the combination of inhaled and systemic antimicrobial agents may have favorably affected clinical outcomes.

401(k) plan asset allocation, account balances, and loan activity.

The Employee Benefit Research Institute (EBRI) and the Investment Company Institute (ICI) have been collaborating for the past two years to collect data on participants in 401(k) plans. This effort, known as the EBRI/ICI Participant-Directed Retirement Plan Data Collection Project, has obtained data for 401(k) plan participants from certain of EBRI and ICI sponsors and members serving as plan recordkeepers and administrators. The report includes 1996 information on 6.6 million active participants in 27,762 plans holding nearly $246 billion in assets. The data include demographic information, annual contributions, plan balances, asset allocation, and loans, and are currently the most comprehensive source of information on individual plan participants. In 1996, the first year for which data are ready for analysis, the EBRI/ICI database appears to be broadly representative of the universe of 401(k) plans. Key findings include: for all participants, 44.0 percent of the total plan balance is invested in equity funds, 19.1 percent in employer stock, 15.1 percent in guaranteed investment contracts (GICs), 7.8 percent in balanced funds, 6.8 percent in bond funds, 5.4 percent in money funds, 0.8 percent in other stable value funds, and 1.0 percent in other or unidentified investments. This allocation implies that over two-thirds of plan balances are invested directly or indirectly in equity securities. Asset allocation varies with age. For instance, on average, individuals in their twenties invested 76.8 percent of assets in equities and only 22.1 percent in fixed-income investments. By comparison, individuals in their sixties invested 53.2 percent of their assets in equities and 45.9 percent of assets in fixed-income investments. Investment options offered by 401(k) plans appear to influence asset allocation. For example, the addition of company stock substantially reduces the allocation to equity funds and the addition of GICs lowers allocations to bond and money funds. Employer contributions in the form of company stock affect participant allocation behavior. Participants in plans in which employer contributions are made in company stock appear to decrease allocations to equity funds and to increase the allocation of company stock in self-directed balances. The average account balance (net of plan loans) for all participants is $37,323. The balances, however, represent only amounts with current employers and do not include amounts remaining in the plans of prior employers. Nor do the balances indicate what savings would be in a "mature" 401(k) plan program. The average balances of older workers with long tenure at one employer indicate that a mature 401(k) plan program will produce substantial account balances. For example, individuals in their sixties with at least 30 years of tenure have average account balances in excess of $156,000; those in their fifties have balances in excess of $117,000.

Morphometric X-ray absorptiometry and morphometric radiography of the spine: a comparison of analysis precision in normal and osteoporotic subjects.

Morphometric techniques, which use conventional lateral spine radiographs to quantify vertebral body shape (morphometric radiography, MRX), have proved a useful tool in the identification and evaluation of osteoporotic vertebral deformities. Recently a new method of acquiring the images required for vertebral morphometry using dual-energy X-ray absorptiometry scanners (morphometric X-ray absorptiometry, MXA) has been developed. In this study we compare repeat analysis precision of vertebral height measurement using MXA and MRX. Twenty-four postmenopausal women were recruited (mean age 67 +/- 5.8 years): 12 normal subjects and 12 with osteoporosis and vertebral deformities. Each subject had a MXA scan and lateral thoracic and lumbar radiographs at a single appointment, which were each analyzed quantitatively in a masked fashion, using a standard 6-point method, twice by one observer and once by a second observer. Anterior (Ha), mid (Hm) and posterior (Hp) vertebral heights were measured and wedge (Ha/Hp) and mid-wedge (Hm/Hp) ratios calculated for each vertebral body. Intra- and interobserver precision were consistently poorer in MXA compared with MRX in both normal subjects and those with vertebral deformities, with MXA CV% generally at least 50% higher than corresponding values for MRX. For both MXA and MRX interobserver precision was clearly poorer than intraobserver precision, a problem associated with any morphometric technique. MXA intra- and interobserver precision were significantly poorer for subjects with vertebral deformities compared with those without, with a CV% for deformity subjects up to twice that of normal subjects. Conversely, MRX showed little or no obvious worsening of intra- or interobserver precision for deformity subjects. Comparison of MXA precision in the normal and deformed vertebrae of the deformity subjects demonstrated that the poorer precision in these subjects compared with normal subjects was the result of increased variability in point placement on the deformed vertebrae themselves. However, the precision for normal vertebrae in these subjects was also somewhat poorer than the precision in normal subjects. We conclude that MXA precision is generally poorer than that of MRX and that the presence of vertebral deformities has a more pronounced effect on MXA precision than on MRX precision.

Comparing effects of the horizontal-vertical illusion on grip scaling and judgment: relative versus absolute, not perception versus action.

The discovery that the prehension component of an open-loop, two-fingered reach is largely immune to certain salient pictorial illusions has been used to suggest that humans possess 2 distinct visual systems, 1 that subserves perceptual judgment and 1 that mediates visually controlled action. In this article, the authors present evidence that suggests that the critical distinction is not that of reaching and judgment but of relative and absolute perception. Experiment 1 extends the findings of S. Aglioti, J. F. X. DeSouza, and M. A. Goodale (1995) and suggests that the manual prehension component of open-loop reaching is affected by the horizontal-vertical illusion to a much smaller degree than perceptual size judgments. In Experiments 2 and 3, however, when perceptual size judgment is directed at a single element of the display, this difference vanishes. Experiment 4 demonstrates that grip scaling is strongly affected by the illusion when a single reach is scaled to both the horizontal and vertical components of a triangular figure.