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BACKGROUND: Although many patients with multivessel coronary artery disease (CAD) and severely depressed left ventricular (LV) function will benefit from coronary artery bypass graft surgery (CABG), surgeons may be reluctant to perform CABG on these patients without evidence of myocardial viability in regions of severe asynergy. We hypothesized that quantitative planar rest-redistribution 201Tl imaging would identify viable myocardium and predict improved regional and global function after revascularization in patients with depressed LV function and CAD. METHODS AND RESULTS: Twenty-one patients (mean LV ejection fraction, 0.27 +/- 0.05) were studied. Regional and global LV functions were evaluated before and 8 weeks after CABG with radionuclide ventriculography. Segments were prospectively classified as showing normal, mildly reduced, or severely reduced viability on the basis of quantitative analysis of defect severity and redistribution on planar resting 201Tl imaging. By 201Tl criteria, 90% of hypokinetic segments were classified with normal or mildly reduced viability. Among akinetic or dyskinetic segments, 20% had normal 201Tl uptake, 53% had mildly reduced viability, and only 27% had severely reduced viability. 201Tl viability criteria identified segments that improved function after CABG. Sixty-two percent of severely asynergic segments with normal viability and 54% with mildly reduced viability improved function after surgery, but only 23% with severely reduced viability improved function (p = 0.002). When only adequately revascularized segments were considered, the predictive value of a positive preoperative viability scan for functional improvement was 73%. The greatest improvement in global LV function after CABG occurred in patients with the greatest number of asynergic segments classified as viable before surgery (p < 0.01). In 10 patients with more than seven viable, asynergic segments, mean LV ejection fraction increased significantly after CABG (0.29 +/- 0.07 to 0.41 +/- 0.11, p = 0.002). In 11 patients with seven or fewer viable, asynergic segments, mean LV ejection fraction remained unchanged after revascularization (0.27 +/- 0.05 to 0.30 +/- 0.08, p = NS). CONCLUSIONS: In patients with CAD and severely depressed LV function, preoperative quantitative planar rest-redistribution. 201Tl imaging identifies viability in many asynergic myocardial segments, and these segments frequently improve function after CABG. The presence of numerous asynergic but viable myocardial segments before surgery correlated significantly with improvement in global LV function after bypass surgery.
OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.
BACKGROUND: To date, it remains unclear to what extent cognitive competence is related to a change in general functional status in older adults. OBJECTIVES: To evaluate both the cross-sectional and the longitudinal relation between cognitive functioning and functional status. METHODS: Sensorimotor speed, memory, and executive functioning were assessed in a large population of healthy adults aged 60 years and older (n = 485) who participated in the Maastricht Aging Study. Data from the baseline (1993-1995), three-year follow-up, and six-year follow-up were used. Functional status was measured using the SF-36, which was coded into a physical and a mental component summary measure. RESULTS: After adjustment for age, sex, and educational level, a high level of cognitive functioning appeared to be associated with better functional status in the cross-sectional analysis. Longitudinal analyses demonstrated, that cognitive functioning was not a predictor of functional status three or six years later. CONCLUSIONS: Thus while cognitive functioning is useful clinically for predicting the short-term functional status of an older person, it is not useful for predicting that person's long-term (>3 years) functional status and thus the period of validity of the results of these tests in answering such questions is limited.
Metamorphosis in holometabolous insects is an ecdysone-dependent process by which the larval form is replaced by a reproductive, adult form. At the onset of metamorphosis ecdysone induces a set of early genes which coordinate tissue-specific responses to hormone. The Broad-Complex (BR-C) early gene, which acts as a global regulator of tissue-specific responses to ecdysone, encodes a family of zinc-finger DNA binding proteins known as Z1, Z2, Z3, and Z4. Genetically the BR-C encodes three complementing functions, br, rbp, and 2Bc, and a class of npr1 alleles that fail to complement any of the other genetic functions. The effects of BR-C mutations on metamorphic development are highly pleiotropic, yet little is known about the roles of individual BR-C proteins in directing the required responses to ecdysone. Because the BR-C is a vital regulator of metamorphosis it is essential to establish the relationships between BR-C genetic functions and protein products. We present here the first general and definitive study of these relationships. Using heat-inducible transgenes we have rescued lethality associated with each of the complementing genetic functions and have restored transcriptional activity of tissue-specific BR-C(+)-dependent target genes. Our data lead us to conclude that br+ function is only provided by the Z2 isoform. We find that Z1 transgenes provide full rbp+ function, while Z4 provides partial function. Likewise, while Z3 provides full 2Bc+ function, Z2 also provides partial function. These results indicate possible functional redundancy or regulatory dependence (via autoregulation) associated with the rbp+ and 2Bc+ functions. The establishment of these relationships between BR-C genetic functions and protein isoforms is an important step toward understanding the roles of BR-C proteins in directing metamorphic responses to ecdysone.
In response to food deprivation, total myocardial lipoprotein lipase activity increased gradually over a period of 9 h. Although lipoprotein lipase exists in a functional and non-functional form in the myocardium, most of the increas in activity occurred in the functional (heparin-releasable) lipoprotein lipase fraction. The administration of colchicine, while having no effect on the increase seen in total lipoprotein lipase activity, did inhibit the increase in the functional fraction, while at the same time, caused a marked rise in the activity of the non-functional (non-releasable) fraction. In rats injected with colchicine after a 24-h fast, total lipoprotein lipase activity was not affected, but activity levels in the functional fraction declined while that in the non-functional fraction increased. These results suggest that the functional lipoprotein lipase is constantly being formed in sites not readily accessible to heparin (presumably the myocardial cells) and transported to its site of action, the surface of the endothelial cells of the capillaries. Cycloheximide administration to rats starved for 24 h caused a decline in activity in both the functional (half-life of about 2 h) and the non-functional (half-life of about 4 h) lipoprotein lipase fractions. These results suggest that the functional and non-functional lipoprotein lipase fractions may correspond to two distinct enzyme species.
OBJECTIVE: To evaluate the feasibility of a new functional tasks exercise program, designed to improve functional performance of community-dwelling older women, by comparing it with a resistance exercise program. DESIGN: A 12-week, randomized, single-blind pilot study. SETTING: A community leisure center. PARTICIPANTS: Twenty-four community-dwelling, medically stable women (mean age, 74.6+/-4.8 y) were randomized to the functional tasks exercises (function group) or the resistance exercises (resistance group). Three participants withdrew from the study. INTERVENTIONS: Exercises were given 3 times weekly for 12 weeks. The functional tasks exercise program aimed to improve daily tasks in the domains first affected in older adults, whereas the resistance exercise program focused on strengthening the muscle groups that are important for functional performance. MAIN OUTCOME MEASURES: Participant satisfaction with the exercises, Assessment of Daily Activity Performance (ADAP), and, as a secondary outcome, muscle strength and power. RESULTS: Exercise adherence was 81% in the function group and 90% in the resistance group. Participants reported greater satisfaction with the resistance exercises than with the functional exercises. The ADAP total score improved with time (P =.001; mean change function group, 7.5 U; 95% confidence interval [CI], 2.1-12.8; resistance group, 2.8 U, 95% CI, -0.4 to 5.9), as did isometric knee extensor strength (P =.001; mean change function group, 6.4%; 95% CI, -1.6 to 14.5; resistance group, 14.4%; 95% CI, 6.4-22.2). Testing for differences in outcomes between the 2 groups showed no statistically significant differences. CONCLUSIONS: The functional tasks exercise program is feasible and shows promise of being more effective for functional performance than a resistance exercise program. A randomized controlled trial with a larger sample size is needed to test the difference between the 2 programs.
This study evaluated the accuracy of experts' predictions of ambulatory function following lower extremity trauma using the Functional capacity index (FCI). Data from three orthopedic trauma studies designed to determine long-term function following specific types of lower extremity injuries were used to examine the extent of agreement between the reported and predicted ambulatory function of 921 subjects. Functional limitations reported by the cohort using a generalized health status measure and more detailed questions on lower extremity function were compared with those predicted by experts based on the injuries sustained. The overall agreement between predicted and self-reported FCI function for ambulation was relatively low (31%). In the majority of cases (80%), the disagreement differed by one functional level. Subjects were more likely to report worse function than predicted by the experts. Multivariate modeling identified different injuries, combinations of injuries, and patient characteristics that significantly influenced agreement. For example, subjects who sustained both a tibia and a femur fracture were three times more likely than subjects who did not sustain either fracture type to report poorer ambulatory function than predicted. Many challenges are faced in predicting long-term function following trauma. More empirical data are needed to inform the process. These data suggest that until the FCI can more accurately predict long-term ambulatory function following different lower extremity injuries, it should not be used for this purpose.
Current structural genomics projects are yielding structures for proteins whose functions are unknown. Accordingly, there is a pressing requirement for computational methods for function prediction. Here we present PHUNCTIONER, an automatic method for structure-based function prediction using automatically extracted functional sites (residues associated to functions). The method relates proteins with the same function through structural alignments and extracts 3D profiles of conserved residues. Functional features to train the method are extracted from the Gene Ontology (GO) database. The method extracts these features from the entire GO hierarchy and hence is applicable across the whole range of function specificity. 3D profiles associated with 121 GO annotations were extracted. We tested the power of the method both for the prediction of function and for the extraction of functional sites. The success of function prediction by our method was compared with the standard homology-based method. In the zone of low sequence similarity (approximately 15%), our method assigns the correct GO annotation in 90% of the protein structures considered, approximately 20% higher than inheritance of function from the closest homologue.
AIM: to compare the two new executive function tests of the revised Cambridge Cognitive Examination (CAMCOG-R), a bedside measure of cognitive function, with existing neuropsychological assessments of executive function in elderly stroke survivors. METHODS: we assessed 83 stroke survivors at 1 and 3 months post-stroke with the new CAMCOG-R, the Weigl colour form sorting test and Raven's coloured progressive matrices. We assessed functional recovery with the Barthel index and depression with the self-report 15-item geriatric depression scale. We used descriptive statistics, Pearson correlation coefficients, paired t-tests and principal axis factor analyses to interpret the data. RESULTS: the new CAMCOG-R executive functioning tests showed moderate correlation with the Weigl and Raven tests (P<0.01). Improved functional outcome as measured by the Barthel index was significantly associated with higher executive function test scores (P<0.05). Depression was significantly associated with poorer performance on all tasks of executive function (P<0.05). A factor analysis of the scores on all of the neuropsychological tests revealed a single strong factor that accounted for 66% of the variance. The CAMCOG-R and the executive functioning subscales used in this population established sensitivity to change over time. CONCLUSION: although the new executive tests of the CAMCOG-R compared reasonably well with the Weigl and Raven neuropsychological tests, the extra time taken to administer the CAMCOG-R may not be justified. The new CAMCOG-R executive function tests were vulnerable to the effects of depression. Finally, the executive function tests might have provided more of a global measure of cognitive function, raising doubts about their construct validity in our patient population.
OBJECTIVE: To evaluate and compare the protective effects of two different perflubron doses on hemodynamics and lung function in a neonatal animal model of cardiopulmonary bypass-induced lung injury. DESIGN: Prospective, randomized, controlled study. SETTING: Animal laboratory of the Department of Surgery, Duke University Medical Center. SUBJECTS: Twenty-one neonatal swine. INTERVENTIONS: One-wk-old swine (2.2-3.2 kg) were randomized to receive cardiopulmonary bypass with full functional residual capacity perflubron (n = 7), cardiopulmonary bypass with half functional residual capacity perflubron (n = 7), or cardiopulmonary bypass alone (n = 7). This last group served as control animals, receiving cardiopulmonary bypass with conventional ventilation. Liquid lung ventilation animals received perflubron via the endotracheal tube at either full functional residual capacity (16-20 mL/kg) or half functional residual capacity (10 mL/kg) before the initiation of cardiopulmonary bypass. Each animal was placed on nonpulsatile cardiopulmonary bypass and cooled to a nasopharyngeal temperature of 18 degrees C (64.4 degrees F). Low-flow cardiopulmonary bypass (35 mL/kg/min) was instituted for 90 mins. The blood flow rate was then returned to 100 mL/kg/min. The animals were warmed to 36 degrees C (96.8 degrees F) and separated from cardiopulmonary bypass. Data were obtained at 30, 60, and 90 mins after separation from cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary bypass without liquid lung ventilation resulted in a significant decrease in cardiac output and oxygen delivery and a significant increase in pulmonary vascular resistance in the post-bypass period. Full functional residual capacity liquid lung ventilation administered before bypass resulted in no change in cardiac output and oxygen delivery after bypass. Full functional residual capacity liquid lung ventilation resulted in lower pulmonary vascular resistance after bypass compared with both control and half functional residual capacity liquid lung ventilation animals. CONCLUSIONS: These data suggest that liquid lung ventilation dosing at full functional residual capacity before bypass is more effective than half functional residual capacity in minimizing the lung injury associated with neonatal cardiopulmonary bypass. Full functional residual capacity dosing may optimize alveolar distention and lung volume, as well as improve oxygen delivery compared with half functional residual capacity dosing.
The purpose of this paper is to investigate the use of a power function as a cost function in inverse planning optimization. The cost function for each structure is implemented as an exponential power function of the deviation between the resultant dose and prescribed or constrained dose. The total cost function for all structures is a summation of the cost function of every structure. When the exponents of all terms in the cost function are set to 2, the cost function becomes a classical quadratic cost function. An independent optimization module was developed and interfaced with a research treatment planning system from the University of North Carolina for dose calculation and display of results. Three clinical cases were tested for this study with various exponents set for tumor targets and sensitive structures. Treatment plans with these exponent settings were compared, using dose volume histograms. The results of our study demonstrated that using an exponent higher than 2 in the cost function for the target achieved better dose homogeneity than using an exponent of 2. An exponent higher than 2 for serial sensitive structures can effectively reduce the maximum dose. Varying the exponent from 2 to 4 resulted in the most effective changes in dose volume histograms while the change from 4 to 8 is less drastic, indicating a situation of saturation. In conclusion, using a power function with exponent greater than 2 as a cost function can effectively achieve homogeneous dose inside the target and/or minimize maximum dose to the critical structures.
It is widely assumed that the distortion characteristics of the cochlea are uniform across its length, or at least across some portion of its length. For each distortion product otoacoustic emission (DPOAE) input/output (I/O) function across frequency, there is a corresponding cochlear I/O function defined over the cochlear source region. An assumption of distortion invariance is adopted such that these cochlear I/O functions are identical across tonotopic place, which is testable in the sense that a single nonlinear function should adequately describe the set of DPOAE I/O functions across frequency. If so, the differences in measured DPOAE I/O functions across frequency are produced by differences in the forward stimulus transmission to the generation site, and reverse DP transmission back to the ear canal. The absolute transfer-function magnitude is not determined by this technique, but the spectral shapes across frequency and between ears are determined. The role of middle-ear functioning is implicit in the I/O functions because of its controlling influence on these transfer functions. Results have been obtained using the average DPOAE I/O functions measured in a population of healthy ears [Gorga et al., J. Acoust. Soc. Am. 107, 2128-2135 (2000)], and support the hypothesis of cochlear-distortion invariance. The measured forward and reverse transfer functions have a general bandpass characteristic, and a more narrow-band structure with similarities to the behavioral threshold curve.
BACKGROUND: Collateral circulation can maintain myocardial function and viability in chronic total coronary occlusion (TCO). The present study evaluates the relation of myocardial function and duration of occlusion to collateral function. METHODS AND RESULTS: A total of 50 patients underwent a successful recanalization of a TCO (>4 weeks' duration). Collateral function was assessed by intracoronary Doppler and pressure recordings before the first balloon inflation and after PTCA had been completed. Collateral function was assessed by Doppler- (CFI(D)) and pressure-derived collateral flow indices (CFI(P)), as well as indices of collateral (R(Coll)) and peripheral resistance (R(P)). Patients with normokinesia had lower R(Coll) (4.9+/-2.5 versus 11.8+/-8.2 mm Hg. cm(-1). s(-1); P=0.033) and lower R(P) (3.8+/-1.9 versus 6.1+/-4.1 mm Hg. cm(-1). s(-1); P=0.031) than those with akinesia. Patients with akinesia and a TCO duration of </=3 months had the highest R(Coll) and R(P), whereas those with akinesia and a longer TCO duration had similar collateral function as patients with normokinesia. After PTCA, CFI(D) and CFI(P) decreased from 0.37+/-0.20 to 0.21+/-0.17 (P<0.001) and from 0.44+/-0.12 to 0.36+/-0.11 (P<0.001), respectively, with an increase in R(Coll) of 139+/-128% (P<0.001) and R(P) by 65+/-99% (P=0.003). This attenuation of collateral function was less pronounced with epicardial collaterals than with intramyocardial collaterals. CONCLUSIONS: Collateral function was better in patients with TCO and normal regional function than in those with impaired regional function. In the latter group, collateral function improvement was time dependent. After recanalization, the recruitable collateral function was attenuated because of an increase of R(Coll) and R(P).
OBJECTIVE: Authors sought to use a cognitive assessment instrument validated for assessing low-functioning patients to broaden knowledge about the rate and correlates of functional decline. METHODS: Patients were examined across a wide range of baseline cognitive and functional status, and changes in cognitive and functional status were examined. A group of 424 elderly patients with schizophrenia were followed up over a 6-year period; 280 of these manifested severe cognitive impairment at baseline. Patients were examined with an instrument designed for cognitive and functional assessment of severe cognitive impairment: the Alzheimer's Disease Assessment Scale-Late (ADAS-L). RESULTS: Patients with higher and lower baseline scores manifested equivalent declines in the ADAS-L cognitive subscale, but differences in decline on basic activities of daily living. Random-effects regression analysis indicated that functional changes were significantly correlated with cognitive changes for the sample as whole and that cognitive changes were the best predictor of changes in functional status over time. Baseline cognitive status was not a statistically significant covariate for functional change, nor was the course of negative symptoms over the follow-up period. CONCLUSIONS: Cognitive change appears very similar in magnitude across older, poor-outcome patients with different baselines of cognitive impairment. In contrast, functional decline was limited to patients with lower levels of functioning at baseline. These findings suggest that cognitive thresholds for impairments in different aspects of functional status may exist in patients with schizophrenia. Basic activities of daily living decline only in patients with very low levels of baseline cognitive functioning.
BACKGROUND: Obesity in pregnancy is increasing and is a risk factor for metabolic pathology such as preeclampsia. In the nonpregnant, obesity is associated with dyslipidemia, vascular dysfunction, and low-grade chronic inflammation. AIM: Our aim was to measure microvascular endothelial function in lean and obese pregnant women at intervals throughout their pregnancies and at 4 months after delivery. Plasma markers of endothelial function, inflammation, and placental function and their association with microvascular function were also assessed. METHODS: Women in the 1st trimester of pregnancy were recruited, 30 with a body mass index (BMI) less than 30 kg/m(2) and 30 with a BMI more than or equal to 30 kg/m(2) matched for age, parity, and smoking status. In vivo endothelial-dependent and -independent microvascular function was measured using laser Doppler imaging in the 1st, 2nd, and 3rd trimesters of pregnancy and at 4 months postnatal. Plasma markers of endothelial activation [soluble intercellular cell adhesion molecule-1 (sVCAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), and plasminogen activator inhibitor (PAI)-1], inflammation (IL-6, TNFalpha, C-reactive protein, and IL-10), and placental function (PAI-1/PAI-2 ratio) were also assessed at each time point. RESULTS: The pattern of improving endothelial function during pregnancy was the same for lean and obese, but endothelial-dependent vasodilation was significantly lower (P < 0.05) in the obese women at each trimester (51, 41, and 39%, respectively). In the postpartum period, the improvement in endothelial-dependent vasodilation persisted in the lean women but declined to near 1st trimester levels in the obese (lean/obese difference, 115%; P < 0.01). There was a small but significant difference in endothelial-independent vasodilation between the two groups, lean response being greater than obese (P = 0.021), and response declined in both groups in the postpartum period. In multivariate analysis, time of sampling had the most impact on endothelial-independent function [18.5% (adjusted sum of squares expressed as a percentage of total means squared), P < 0.001 for sodium nitroprusside response; 9.8%, P < 0.001 for acetylcholine response], and obesity had the most impact on endothelial-dependent microvascular function (1.7%, P = 0.046 for sodium nitroprusside response; 19.3%, P < 0.001 for acetylcholine response). Time of sampling (11.2%, P < 0.001), IL-6 (4.0%, P = 0.002), and IL-10 (2.4%, P = 0.018) were significant independent contributors to variation in endothelial-dependent microvascular function. When obesity was entered into the model, the association with IL-6 and IL-10 was no longer significant, and obesity explained 6.8% (P < 0.001) of the variability in endothelial-dependent microvascular function. In the 1st trimester, obese women had a significantly higher PAI-1/PAI-2 ratio [obese median (interquartile range), 0.87 (0.54-1.21) vs. lean 0.30 (0.21-0.47), P < 0.001), reflecting the lower PAI-2 levels in obese pregnant women. In a multivariate analysis, 1st trimester BMI (7.6%, P = 0.012), IL-10 (8.2%, P < 0.001), and sVCAM-1 (0.73%, P = 0.007) contributed to the 1st trimester PAI-1/PAI-2 ratio. CONCLUSION: Obese mothers have a lower endothelium-dependent and -independent vasodilation when compared with lean counterparts. There was a higher PAI-1/ PAI-2 ratio in the 1st trimester in obese women, which improved later in pregnancy. Obese pregnancy is associated with chronic preexisting endothelial activation and impairment of endothelial function secondary to increased production of inflammatory T-helper cells-2 cytokines.
PURPOSE: We retrospectively reviewed a consecutive series of patients who underwent pyeloplasty. In all cases preoperative and postoperative isotope renal scans were performed to assess the surgical outcome with particular emphasis on the change in renal function postoperatively. MATERIALS AND METHODS: The clinical records of 108 consecutive children with ureteropelvic junction obstruction were reviewed. Individual renal function was evaluated and obstruction was confirmed by diuretic assisted 99mtechnetium diethylenetriaminepentaacetic acid or mercaptoacetyltriglycine renography. A total of 100 pyeloplasties in 98 children between 5 days and 16 years old was included. Results were analyzed by groups according to patient age and symptoms at presentation. RESULTS: Drainage half-times improved in 98% of patients and only 1 required reoperation. Improved renal function greater than 5% was noted in about a third of each age group. Function remained stable in 68% of the kidneys and decreased in only 1. Of the improved kidneys 77% had impaired function preoperatively (40% or less of the total contribution). Those presenting with a renal mass had the greatest improvement in function. There was no statistically significant difference in improvement in renal function by age group or patient presentation. Regression analysis revealed that preoperative differential renal function was the only statistically significant predictor of improvement in renal function after pyeloplasty. CONCLUSIONS: Pyeloplasty in children is safe and renal functional improvement can be expected in the majority of kidneys with impaired function at presentation. However, there was no indication that early pyeloplasty in infants is more likely to result in improved function than in older children.