Citations

ABSTRACT We previously showed that the cysteines flanking the internal fusion peptide of the avian sarcoma/leukosis virus subtype A (ASLV-A) Env (EnvA) are important for infectivity and cell-cell fusion. Here we define the stage of fusion at which the cysteines are required. The flanking cysteines are dispensable for receptor-triggered membrane association but are required for the lipid mixing step of fusion, which, interestingly, displays a high pH onset and a biphasic profile. Second-site mutations that partially restore infection partially restore lipid mixing. These findings indicate that the cysteines flanking the internal fusion peptide of EnvA (and perhaps by analogy Ebola virus glycoprotein) are important for the foldback stage of the conformational changes that lead to membrane merger.

Elasticity imaging is an emerging medical imaging modality. Methods involving acoustic radiation force excitation and pulse-echo ultrasound motion detection have been investigated to assess the mechanical response of tissue. In this work new methods for dynamic radiation force excitation and motion detection are presented. The theory and model for harmonic motion detection of a vibrating reflective target are presented. The model incorporates processing of radio frequency data acquired using pulse-echo ultrasound to measure harmonic motion with amplitudes ranging from 100to10,000nm. A numerical study was performed to assess the effects of different parameters on the accuracy and precision of displacement amplitude and phase estimation and showed how estimation errors could be minimized. Harmonic pulsed excitation is introduced as a multifrequency radiation force excitation method that utilizes ultrasound tonebursts repeated at a rate fr. The radiation force, consisting of frequency components at multiples of fr, is generated using 3.0MHz ultrasound, and motion detection is performed simultaneously with 9.0MHz pulse-echo ultrasound. A parameterized experimental analysis showed that displacement can be measured with small errors for motion with amplitudes as low as 100nm. The parameterized numerical and experimental analyses provide insight into how to optimize acquisition parameters to minimize measurement errors.

Abstract Rationale Adenotonsillectomy, the first line of treatment of sleep-disordered breathing (SDB), is the most commonly performed pediatric surgery. Predictors of the recurrence of SDB after adenotonsillectomy and its impact on cardiovascular risk factors have not been identified. Objectives Demonstrate that gain velocity in body mass index (BMI) defined as unit increase in BMI/year confers an independent risk for the recurrence of SDB 1 year after adenotonsillectomy. Methods Children with SDB and hypertrophy of the tonsils and a comparison group of healthy children were followed prospectively for 1 year. Measurements and Main Results Serial polysomnographies, BMI, and blood pressure were obtained before adenotonsillectomy and 6 weeks, 6 months, and 1 year postoperatively. Gain velocity in BMI, BMI and being African American (odds ratios, 4–6/unit change/yr; 1.4/unit and 15, respectively) provided equal amounts of predictive power to the risk of recurrence of SDB. In the group that experienced recurrence, systolic blood pressure at 1 year was higher than at baseline and higher than in children who did not experience recurrence. Conclusions Three clinical parameters confer independent increased risk for high recurrence of SDB after adenotonsillectomy: gain velocity in BMI, obesity, and being African American. A long-term follow-up of children with SDB and monitoring of gain velocity in BMI are essential to identifying children at risk for recurrence of SDB and in turn at risk for hypertension.

Abstract Purpose. Previous studies have found that marriage is associated with longer survival and better quality of life among lung cancer patients. The present study used the Mayo Clinic Lung Cancer Cohort to re-examine this issue. Methods. In total, 5,898 non-small cell lung cancer (NSCLC) patients, who had available information on marital status and who had been enrolled in the Mayo Clinic Lung Cancer Cohort (MCLCC), were the focus of this study. Patients had extensive baseline and follow-up data on cancer stage, cancer treatment, and prognostic factors. All patients had been followed within the MCLCC with at least annual confirmation of vital status and patient-reported quality of life (the Lung Cancer Symptom Scale and the Linear Analogue Scales of Assessment). Results. The numbers of patients who were married, single, divorced, and widowed at the time of cancer diagnosis were 4,457 (76%), 265 (4%), 440 (7%), and 736 (12%), respectively. No statistically significant difference in survival was observed among these four groups, even after adjusting for a variety of prognostic factors, such as age, gender, and tumor stage. However, exploratory analyses suggested that widowed and divorced patients received less aggressive cancer therapy, and certain patient subgroups, such as stage IA widowed patients, had a shorter survival. Divorced patients reported greater financial concerns, and married and widowed patients reported greater spirituality and better social support. Conclusion. This study did not observe differences in survival or quality of life based on marital status at the time of diagnosis of NSCLC, but subgroup analyses appear to suggest findings worthy of further exploration.

Questions remain as to whether pediatric sleep disordered breathing increases the risk for elevated blood pressure and blood pressure–dependent cardiac remodeling. We tested the hypothesis that activity-adjusted morning blood pressure surge, blood pressure load, and diurnal and nocturnal blood pressure are significantly higher in children with sleep disordered breathing than in healthy controls and that these blood pressure parameters relate to left ventricular remodeling. 24-hour ambulatory blood pressure parameters were compared between groups. The associations between blood pressure and left ventricular relative wall thickness and mass were measured. 140 children met the inclusion criteria. In children with apnea hypopnea index <5 per hour, a significant difference from controls was the morning blood surge. Significant increases in blood pressure surge, blood pressure load, and in 24-hour ambulatory blood pressure were evident in those whom the apnea hypopnea index exceeded 5 per hour. Sleep disordered breathing and body mass index had similar effect on blood pressure parameters except for nocturnal diastolic blood pressure, where sleep disordered breathing had a significantly greater effect than body mass index. Diurnal and nocturnal systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure predicted the changes in left ventricular relative wall thickness. Therefore, sleep disordered breathing in children who are otherwise healthy is independently associated with an increase in morning blood pressure surge, blood pressure load, and 24-hour ambulatory blood pressure. The association between left ventricular remodeling and 24-hour blood pressure highlights the role of sleep disordered breathing in increasing cardiovascular morbidity.

Medical and surgical emergencies occasionally present as ruptured abdominal aortic aneurysms (RAAA). To assess benefits of laparotomies and adverse effects of unnecessary operations, the authors reviewed their experience. Thirteen patients, 9 women, 4 men (mean age: 72 years, range: 41-85) underwent emergency laparotomy between 1988 and 1996 for presumed RAAA and were found to have other surgical or medical emergencies. All the patients presented with hypotension, 12 had abdominal or back pain, four had pulsatile abdominal mass. Rupture was not excluded by computed tomography scan in three or by ultrasonography in two patients. Laparotomy disclosed intact abdominal aorta in all, but seven patients had abdominal aortic aneurysm. Of five surgical emergencies, laparotomy was indicated in four: three for ruptured visceral artery aneurysms, one for perforated duodenal ulcer. The fifth patient required thoracotomy for ruptured thoracic aneurysm. Four of eight medical emergencies were myocardial infarctions. One iatro genic complication required reoperation for bleeding. Mean hospital stay was 18 days; mean hospital charges were $40,771. Seven (54%) early deaths occurred; none were caused directly by the operation. Laparotomy was indicated in one third of deceptive emergencies that present as RAAA. Although mortality, morbidity, and costs were high, iatrogenic surgical complica tions were rare and deaths were not caused by unnecessary operations.

Background— Patients with primary amyloidosis (AL type) have a poor prognosis, in part due to frequent cardiac involvement. Although intracardiac thrombus has been reported in anecdotal cases, neither its frequency nor its role in causing mortality is known. Furthermore, the clinical and echocardiographic variables that may be associated with thromboembolism in cardiac amyloidosis have not been defined. Methods and Results— A total of 116 autopsy or explanted cases of cardiac amyloidosis (55 AL and 61 other type) were identified in the Mayo Clinic. Forty-six fatal nonamyloid trauma cases served as controls. Each heart was examined for intracardiac thrombus. The cause of death was determined from autopsy and clinical notes. Intracardiac thrombosis was identified in 38 hearts (33%). Twenty-three had 1 thrombus, whereas 15 had 2 to 5 thrombi. Although subjects in the AL group were younger and had less atrial fibrillation than those with other types of amyloidosis, the AL group had significantly more intracardiac thrombus (51% versus 16%, P <0.001) and more fatal embolic events (26% versus 8%, P <0.03). Control hearts had no intracardiac thrombus. The presence of both atrial fibrillation and AL was associated with an extremely high risk for thromboembolism (odds ratio 55.0 [95% confidence interval 8.1 to 1131.4]). By multivariate analysis, AL type (odds ratio 8.4 [95% confidence interval 1.8 to 51.2]) and left ventricular diastolic dysfunction (odds ratio 12.2 [95% confidence interval 2.7 to 72.7]) were independently associated with thromboembolism. Conclusions— A high frequency of intracardiac thrombosis was present in cardiac amyloidosis. Furthermore, thromboembolism caused significant fatality. Several risk factors for thromboembolism were identified. Early screening, especially in high-risk patients, and early anticoagulation might reduce morbidity and mortality.