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Robert D Stewart

Publications and source records attributed to Robert D Stewart.

17 recordsLinked to original sources
PubMed2006

A physiologically plausible model of action selection and oscillatory activity in the basal ganglia.

The basal ganglia (BG) have long been implicated in both motor function and dysfunction. It has been proposed that the BG form a centralized action selection circuit, resolving conflict between multiple neural systems competing for access to the final common motor pathway. We present a new spiking neuron model of the BG circuitry to test this proposal, incorporating all major features and many physiologically plausible details. We include the following: effects of dopamine in the subthalamic nucleus (STN) and globus pallidus (GP), transmission delays between neurons, and specific distributions of synaptic inputs over dendrites. All main parameters were derived from experimental studies. We find that the BG circuitry supports motor program selection and switching, which deteriorates under dopamine-depleted and dopamine-excessive conditions in a manner consistent with some pathologies associated with those dopamine states. We also validated the model against data describing oscillatory properties of BG. We find that the same model displayed detailed features of both gamma-band (30-80 Hz) and slow (approximately 1 Hz) oscillatory phenomena reported by Brown et al. (2002) and Magill et al. (2001), respectively. Only the parameters required to mimic experimental conditions (e.g., anesthetic) or manipulations (e.g., lesions) were changed. From the results, we derive the following novel predictions about the STN-GP feedback loop: (1) the loop is functionally decoupled by tonic dopamine under normal conditions and recoupled by dopamine depletion; (2) the loop does not show pacemaking activity under normal conditions in vivo (but does after combined dopamine depletion and cortical lesion); (3) the loop has a resonant frequency in the gamma-band.

Action Potentials↗
PubMed2006

On the biophysical interpretation of lethal DNA lesions induced by ionising radiation.

Although DNA damage is widely viewed as a critical target for the induction of cell killing by ionising radiation, the exact nature of DNA damage responsible for these effects is unknown. To address this issue, the probability of forming lethal damage by single proton tracks, derived from published survival data for Chinese hamster V79 cells irradiated by protons with energies from 0.57 to 5.01 MeV, has been compared to estimated yields of clustered DNA lesions and repair outcomes calculated with Monte Carlo models. The reported studies provide new information about the potential relationship between the induction and repair of clustered DNA damage and trends in the expected number of lethal events for protons with increasing linear energy transfer (LET). A good correlation was found between the number of lethal events in V79 cells and the induction of double-strand breaks (DSBs) consisting of three or more elementary DNA lesions. For the yields of other types of DNA damage, as well as point mutations formed through the misrepair of base damage and single-strand breaks, observed trends with increasing LET are not consistent with trends in the yields of lethal events. This observation suggests that the relative biological effectiveness (RBE) of protons of varying quality may be more closely related to the induction of complex DSBs rather than other forms of damage.

Animals↗
PubMed2006

Use of partial cardiopulmonary bypass for coarctation repair through a left thoracotomy in children without collaterals.

BACKGROUND: Paraplegia is a devastating complication of coarctation of the aorta (COA) repair. Since 1990 we have used left atrium-to-descending aorta cardiopulmonary bypass (CPB) for COA repair in patients with inadequate collaterals. We reviewed the results with that strategy and compared this CPB group with COA repairs in which CPB was not used to see whether there was any increase in morbidity or delay in recovery. METHODS: From 1990 to 2006, 11 patients with COA were identified to have inadequate collaterals based on preoperative examination and intraoperative arterial monitoring and test clamp. Left thoracotomy with left atrium-to-descending aorta CPB was used in all. Age ranged from 4.2 to 17.4 years (mean, 8.7 +/- 4.6 years). Two were reoperations for recurrent COA, 3 patients had four prior transcatheter balloon dilatations. One patient had aberrant origin of the right subclavian artery. Operative techniques included resection with extended end-to-end anastomosis (n = 6), interposition graft (n = 4), and patch repair (n = 1). During the same period 71 patients older than 1 year of age had COA repair without CPB. Age ranged from 1.1 to 46.1 years (mean, 7.6 +/- 7.1 years; p = 0.6). RESULTS: Preoperative imaging of CPB patients demonstrated absence of collaterals (n = 7), possible collaterals (n = 2), small collaterals (n = 1), and anomalous origin of the right subclavian artery (n = 1). Preoperative arm leg gradient in CPB patients was 36.0 +/- 9.0 mm Hg versus 49.9 +/- 15 mm Hg in non-CPB patients (p < 0.01). Mean distal femoral artery pressure with aortic test clamp was 34.3 +/- 4.8 mm Hg in CPB patients versus 49.8 +/- 12.4 mm Hg in non-CPB patients (p < 0.01). Mean CPB flow was 53% +/- 7.3% of calculated total flow. Cardiopulmonary bypass time ranged from 17 to 46 minutes (mean, 27.5 +/- 9.7 minutes). Aortic clamp time in CPB patients ranged from 15 to 33 minutes (mean, 21.6 +/- 6.3 minutes). In the non-CPB group aortic clamp time ranged from 10 to 50 minutes (mean, 23.4 +/- 7.5 minutes; p = 0.5). In the CPB group length of stay ranged from 3 to 7 days (mean, 4.9 +/- 1.3 days), and in the non-CPB group length of stay ranged from 3 to 12 days (mean, 4.7 +/- 1.4 days; p = 0.5). No patient had a neurologic complication. There were no other major complications in the CPB group (eg, bleeding, recurrent laryngeal nerve injury, re-COA). CONCLUSIONS: Preoperative imaging and a lower arm-to-leg gradient in this series of COA patients suggested inadequate collateral circulation with the potential need for CPB. A femoral artery pressure of less than 45 mm Hg during test clamp was used as an indication for partial CPB. The use of left atrium-to-descending aorta CPB with just over 50% calculated total flow protected the spinal cord in a safe and expeditious fashion. Use of left heart bypass did not affect morbidity or recovery time as compared with COA repair in non-CPB patients.

Adolescent↗
PubMed2006

Neutron scattered dose equivalent to a fetus from proton radiotherapy of the mother.

Scattered neutron dose equivalent to a representative point for a fetus is evaluated in an anthropomorphic phantom of the mother undergoing proton radiotherapy. The effect on scattered neutron dose equivalent to the fetus of changing the incident proton beam energy, aperture size, beam location, and air gap between the beam delivery snout and skin was studied for both a small field snout and a large field snout. Measurements of the fetus scattered neutron dose equivalent were made by placing a neutron bubble detector 10 cm below the umbilicus of an anthropomorphic Rando phantom enhanced by a wax bolus to simulate a second trimester pregnancy. The neutron dose equivalent in milliSieverts (mSv) per proton treatment Gray increased with incident proton energy and decreased with aperture size, distance of the fetus representative point from the field edge, and increasing air gap. Neutron dose equivalent to the fetus varied from 0.025 to 0.450 mSv per proton Gray for the small field snout and from 0.097 to 0.871 mSv per proton Gray for the large field snout. There is likely to be no excess risk to the fetus of severe mental retardation for a typical proton treatment of 80 Gray to the mother since the scattered neutron dose to the fetus of 69.7 mSv is well below the lower confidence limit for the threshold of 300 mGy observed for the occurrence of severe mental retardation in prenatally exposed Japanese atomic bomb survivors. However, based on the linear no threshold hypothesis, and this same typical treatment for the mother, the excess risk to the fetus of radiation induced cancer death in the first 10 years of life is 17.4 per 10,000 children.

Female↗
PubMed2006

Effects of oxygen on intrinsic radiation sensitivity: A test of the relationship between aerobic and hypoxic linear-quadratic (LQ) model parameters.

The poor treatment prognosis for tumors with high levels of hypoxia is usually attributed to the decreased sensitivity of hypoxic cells to ionizing radiation. Mechanistic considerations suggest that linear quadratic (LQ) survival model radiosensitivity parameters for hypoxic (H) and aerobic (A) cells are related by alphaH = alphaA/oxygen enhancement ratio (OER) and (alpha/beta)H=OER(alpha/beta)A. The OER parameter may be interpreted as the ratio of the dose to the hypoxic cells to the dose to the aerobic cells required to produce the same number of DSBs per cell. The validity of these expressions is tested against survival data for mammalian cells irradiated in vitro with low- and high-LET radiation. Estimates of hypoxic and aerobic radiosensitivity parameters are derived from independent and simultaneous least-squares fits to the survival data. An external bootstrap procedure is used to test whether independent fits to the survival data give significantly better predictions than simultaneous fits to the aerobic and hypoxic data. For low-LET radiation, estimates of the OER derived from the in vitro data are between 2.3 and 3.3 for extreme levels of hypoxia. The estimated range for the OER is similar to the oxygen enhancement ratios reported in the literature for the initial yield of DSBs. The half-time for sublethal damage repair was found to be independent of oxygen concentration. Analysis of patient survival data for cervix cancer suggests an average OER less than or equal to 1.5, which corresponds to a pO2 of 5 mm Hg (0.66%) in the in vitro experiments. Because the OER derived from the cervix cancer data is averaged over cells at all oxygen levels, cells irradiated in vivo under extreme levels of hypoxia (<0.5 mm Hg) may have an OER substantially higher than 1.5. The reported analyses of in vitro data, as well as mechanistic considerations, provide strong support for the expressions relating hypoxic and aerobic radiosensitivity parameters. The formulas are also useful for the analysis of clinical data because the number of radiosensitivity parameters that need to be determined is reduced from four to three without a substantial decrease in the ability of the LQ to accurately predict the surviving faction. The relationships among radiosensitivity parameters imply that the dose to the hypoxic subvolume of the tumor needs to be escalated by a factor of the OER to achieve the same level of tumor control as in well oxygenated tumor regions.

Apoptosis↗
PubMed2005

Atrioventricular valve procedures with repeat fontan operations: influence of valve pathology, ventricular function, and arrhythmias on outcome.

BACKGROUND: The purpose of this study is to analyze atrioventricular valve procedures when performed in association with repeat Fontan operations and to determine the influence of atrioventricular valvar pathology, ventricular function, and arrhythmias on outcome. METHODS: Between December 1994 and August 2004, 80 patients had repeat Fontan operations that included arrhythmia surgery (78 of 80), venous pathway revision (78 of 80), atrioventricular valve repair-replacement (15 of 80), and other associated procedures. Mean ages were the following: at operation, 20.3 +/- 8.4 years; at prior Fontan, 7.1 +/- 5.8 years. Atrioventricular valve procedures were performed on 8 functionally mitral and 7 functionally tricuspid valves. The average cross-clamp and cardiopulmonary bypass times were 61.9 +/- 42.8 minutes and 218 +/- 82 minutes, respectively. RESULTS: Ventricular dysfunction (8% vs 54%, p < 0.0001), valvar dysfunction (13% vs 25%, p < 0.05), and atrial arrhythmias (18% vs 86%, p < 0.0001) increased during the preceding 12.0 +/- 4.7 years before the most recent Fontan operation. Multivariate analysis for death, orthotopic cardiac transplantation (OCT), or renal dialysis showed severe ventricular dysfunction, age greater than 25 years, right or ambiguous functional ventricle, and ischemic time greater than 100 minutes to be highly significant. Notably, cardiac index, elevated end diastolic pressure, and atrial fibrillation were not predictors of outcome. Mitral valve repairs were inconsistent due to probable technical misjudgments; most tricuspid valves could not be repaired. Operative and late mortality were 1.2% and 5.0%, respectively. Emergent and late OCT were 1.2% and 3.7%, respectively. CONCLUSIONS: Risk factors for poor outcome are severe ventricular dysfunction, right or ambiguous single ventricle, age greater than 25 years, and ischemic time greater than 100 minutes. Mitral valves are potentially more amenable to repair than are tricuspid valves. Prosthetic valve replacement should be considered when valve repair is questionable.

Adolescent↗
PubMed2005

Tetralogy of Fallot: results of a pulmonary valve-sparing strategy.

BACKGROUND: Our surgical strategy for repair of tetralogy of Fallot has focused on preserving the pulmonary valve. The purpose of this review was to identify pulmonary valve characteristics that mark the limits of this strategy. METHODS: From 1997 through 2004, 102 consecutive patients underwent repair of tetralogy of Fallot at a median age of 5.9 months. Twenty-five patients had a prior shunt. Eighty-two patients (80%) had pulmonary valve-sparing procedures, predominantly through a transatrial and transpulmonary approach (n = 52). Twenty patients had a transannular patch (20%). Intraoperative measurements included the pulmonary valve annulus size and the postoperative pressure ratio between the right and left ventricles. RESULTS: Eighty of 85 (94%) patients with z-score greater than -4 had a pulmonary valve-sparing procedure compared with 2 of 17 patients (12%) with pulmonary valve annulus z-scores less than -4 (p < 0.0001). All patients with a tricuspid pulmonary valve (n = 26) had a pulmonary valve-sparing procedure compared with 56 of 76 (74%) patients with a bicuspid pulmonary valve (p = 0.0016). Five patients with initial pulmonary valve-sparing operations required reoperation for residual stenoses; 4 pulmonary valve-sparing right ventricular outflow tract resections and 1 transannular patch. The only death occurred after reoperation elsewhere. Three of 9 patients (33%) who had a postoperative pressure ratio between the right and left ventricles greater than 0.7 after their initial pulmonary valve-sparing procedure required reoperation compared with 2 of 73 with postoperative pressure ratio between the right and left ventricles less than 0.7 (3%; p = 0.008). Fifteen of 25 patients (60%) with prior shunts had pulmonary valve-sparing procedures. CONCLUSIONS: A pulmonary valve-sparing approach to the repair of tetralogy of Fallot was applied successfully in 80% of patients. Significant markers for success were a measured pulmonary annulus z-score of -4 or larger, a tricuspid pulmonary valve, and a postoperative pressure ratio between the right and left ventricles less than 0.7.

Female↗
PubMed2005

The case against minimally invasive cardiac surgery.

Stellar outcomes have been achieved for patent ductus arteriosus (PDA), atrial septal defect (ASD), and ventricular septal defect (VSD) repairs by using the traditional surgical methods. Over the last decade, minimally invasive procedures have been introduced that promise excellent results with an improved cosmetic appearance, shorter rehabilitation period, less pain, and decreased hospital cost. We reviewed various minimally invasive procedures that are used in PDA, ASD, and VSD to assess their safety and efficacy. These techniques use limited approaches to the heart (partial sternotomies, transxiphoid, anterolateral thoracotomy, and mini-thoracotomy) that reduce the surgeons access and control of the cardiac structures. Cannulation sites for the establishment of cardiopulmonary bypass have been altered. Minimally invasive therapies for congenital heart surgery cannot be adopted until evidence-based data has proven them to be equal or better than the traditional procedure.

Cardiac Surgical Procedures↗
PubMed2004

Comparison of in vitro and in vivo alpha/beta ratios for prostate cancer.

Parallel in vitro and in vivo studies provide insight into the relationship between clinical response and intrinsic cellular radiosensitivity and may aid in the development of predictive assays. Compilations of radiosensitivity parameters from in vitro experiments can also be used to examine the potential effectiveness of alternative or new treatment plan designs until enough clinical data become available to directly estimate the requisite radiosensitivity parameters. In this work, survival data for six prostate cancer cell lines (ten datasets total) have been extracted from the literature and re-analysed using the linear-quadratic (LQ) survival model. The paired bootstrap technique for regression is used to compute 95% confidence intervals for the estimated radiosensitivity parameters. LQ radiosensitivity parameters derived from the in vitro data are then compared to radiosensitivity parameters derived from clinical data for prostate cancer. Estimates of alpha range from 0.09 to 0.35 Gy(-1) (all cell lines), and the alpha/beta ratio ranges from 1.09 to 6.29 Gy (all cell lines). Point estimates of the repair half-time (PPC-1, TSU-Pr1, PC-3 and DU-145 cell lines) range from 5.7 to 8.9 h (95% confidence interval from 0.26 h to 10.7 h). Differences in the radiosensitivity parameters determined from the data reported by different laboratories are as large as or larger than the differences in radiosensitivity parameters observed among the various prostate cell lines. The reported studies demonstrate that even seemingly small corrections for dose rate effects, such as those expected in high dose rate (HDR) experiments, can sometimes have a significant impact on estimates of alpha and alpha/beta. By neglecting dose rate effects in the analysis of HDR experiments, estimates of the alpha/beta, ratio may be too high by factors as large as 1.3 to 6.2. The half-time for repair derived from the in vitro experiments appears significantly larger (slower repair rate) than estimates derived from the clinical data. However, the prostate radiosensitivity parameters alpha and alpha/beta may be approximately the same in vitro and in vivo. Most of the in vitro data are consistent with an alpha/beta ratio for prostate cancer less than 3 or 4 Gy.

Alpha Particles↗
PubMed2003

Impact of prolonged fraction delivery times on tumor control: a note of caution for intensity-modulated radiation therapy (IMRT).

PURPOSE: Intensity-modulated radiation therapy (IMRT) allows greater dose conformity to the tumor target. However, IMRT, especially static delivery, usually requires more time to deliver a dose fraction than conventional external beam radiotherapy (EBRT). The purpose of this work is to explore the potential impact of such prolonged fraction delivery times on treatment outcome. METHODS AND MATERIALS: The generalized linear-quadratic (LQ) model, which accounts for sublethal damage repair and clonogen proliferation, was used to calculate the cell-killing efficiency of various simulated and clinical IMRT plans. LQ parameters derived from compiled clinical data for prostate cancer (alpha = 0.15 Gy(-1), alpha/beta = 3.1 Gy, and a 16-min repair half-time) were used to compute changes in the equivalent uniform dose (EUD) and tumor control probability (TCP) due to prolonged delivery time of IMRT as compared with conventional EBRT. EUD and TCP calculations were also evaluated for a wide range of radiosensitivity parameters. The effects of fraction delivery times ranging from 0 to 45 min on cell killing were studied. RESULTS: Our calculations indicate that fraction delivery times in the range of 15-45 min may significantly decrease cell killing. For a prescription dose of 81 Gy in 1.8 Gy fractions, the EUD for prostate cancer decreases from 78 Gy for a conventional EBRT to 69 Gy for an IMRT with a fraction delivery time of 30 min. The values of EUD are sensitive to the alpha/beta ratio, the repair half-time, and the fraction delivery time. The instantaneous dose-rate, beam-on time, number of leaf shapes (segments), and leaf-sequencing patterns given the same overall fraction delivery time were found to have negligible effect on cell killing. CONCLUSIONS: The total time to deliver a single fraction may have a significant impact on IMRT treatment outcome for tumors with a low alpha/beta ratio and a short repair half-time, such as prostate cancer. These effects, if confirmed by clinical studies, should be considered in designing IMRT treatments.

DNA Damage↗
PubMed2003

Dose escalation in permanent brachytherapy for prostate cancer: dosimetric and biological considerations.

No prospective dose escalation study for prostate brachytherapy (PB) with permanent implants has been reported. In this work, we have performed a dosimetric and biological analysis to explore the implications of dose escalation in PB using 125I and 103Pd implants. The concept of equivalent uniform dose (EUD), proposed originally for external-beam radiotherapy (EBRT), is applied to low dose rate brachytherapy. For a given 125I or 103Pd PB, the EUD for tumour that corresponds to a dose distribution delivered by EBRT is calculated based on the linear quadratic model. The EUD calculation is based on the dose volume histogram (DVH) obtained retrospectively from representative actual patient data. Tumour control probabilities (TCPs) are also determined in order to compare the relative effectiveness of different dose levels. The EUD for normal tissue is computed using the Lyman model. A commercial inverse treatment planning algorithm is used to investigate the feasibility of escalating the dose to prostate with acceptable dose increases in the rectum and urethra. The dosimetric calculation is performed for five representative patients with different prostate sizes. A series of PB dose levels are considered for each patient using 125I and 103Pd seeds. It is found that the PB prescribed doses (minimum peripheral dose) that give an equivalent EBRT dose of 64.8, 70.2, 75.6 and 81 Gy with a fraction size of 1.8 Gy are 129, 139, 150 and 161 Gy for 125I and 103, 112, 122 and 132 Gy for 103Pd implants, respectively. Estimates of the EUD and TCP for a series of possible prescribed dose levels (e.g., 145, 160, 170 and 180 Gy for 125I and 125, 135, 145 and 155 for 103Pd implants) are tabulated. The EUD calculation was found to depend strongly on DVHs and radiobiological parameters. The dosimetric calculations suggest that the dose to prostate can be escalated without a substantial increase in both rectal and urethral dose. For example, increasing the PB prescribed dose from 145 to 180 Gy increases EUD for the rectum by only 3%. Our studies indicate that the dose to urethra can be kept within 100-120% of the prescription dose for all the dose levels studied. In conclusion, dose escalation in permanent implant for localized prostate cancer may be advantageous. It is dosimetrically possible to increase dose to prostate without a substantial increase in the dose to the rectum and urethra. Based on the results of our studies, a prospective dose escalation trial for prostate permanent implants has been initiated at our institution.

Cell Survival↗
PubMed2003

Mitochondrial DNA deletions in coronary artery bypass grafting patients.

OBJECTIVE: Mitochondrial DNA (mitoDNA) deletions have been shown to increase with aging and ischemia and have been suggested to contribute to myocardial dysfunction. The purpose of this study was to determine the prevalence and specificity of mitoDNA deletions in coronary artery bypass patients. METHODS: Right atrial appendix tissue from 51 cardiac surgical patients (30-93 years; mean 64+/-14 years) was obtained during cardiopulmonary bypass cannulation (Control), just prior to the removal of the venous cannula (Ischemia, 169+/-38 min) and following removal of the cannula (Reperfusion) and used for polymerase chain reaction (PCR) and sequence analysis. RESULTS: A novel mitoDNA deletion (approximately 7.3 kb, mitoDNA(7.3)) was found in three unrelated, male patients (53, 67, 75 years old). All mitoDNA(7.3) deletion breakpoints were found downstream of the ATP synthase 8 genes and at the 3' end of the cytochrome b genes. The prevalence of the mitoDNA(7.3) deletion was significantly increased (P<0.05) following ischemia and reperfusion. Clinical data indicated that postoperative left ventricular ejection fraction was lower (38.3 vs. 46.4%), and the incidence of previous myocardial infarction higher (1.7 vs. 0.6) in patients exhibiting mitoDNA deletions. CONCLUSION: Our results reveal a novel mitochondrial DNA deletion occurring within the genome region coding for the mitochondrial genes of oxidative phosphorylation that is significantly increased during ischemia and reperfusion. The incidence and prevalence of mitoDNA(7.3) deletions in patients with clinical indications of poor recovery suggests that mitoDNA(7.3) deletions may provide an important indicator to surgical outcome in the cardiac surgical patient.

Adult↗
PubMed2002

Equivalence of the linear-quadratic and two-lesion kinetic models.

Double strand breaks (DSBs) are widely accepted as the main type of DNA damage responsible for cell killing in the range of doses and dose rates relevant to radiation therapy. Although the standard linear-quadratic (LQ) model with one first-order repair term often suffices to explain the results of some radiobiological experiments, converging lines of evidence suggest that DSBs are rejoined at two or more distinct rates. A two-lesion kinetic (TLK) model has been proposed to provide a direct link between biochemical processing of the DSBs and cell killing. A defining feature of the TLK model is that the family of all possible DSBs is subdivided into simple and complex DSBs, and each kind may have its own unique repair characteristics. Break-ends associated with both kinds of DSB are allowed to interact in pairwise fashion to form irreversible lethal and non-lethal chromosome aberrations. This paper examines the theoretical and practical linkages between the TLK and LQ models. The TLK formalism is used to derive an LQ formula with two first-order repair terms (dose protraction factors) and to relate the intrinsic radiosensitivity parameters used in one model to the parameters used in the other. Two extensive radiobiological datasets, one for CHO 10B2 cells and one for C3H 10T1/2 cells, are analysed using the TLK and LQ models. The LQ with two repair terms and the TLK are equally capable of explaining the CHO 10B2 and C3H 10T1/2 cell survival data. For the doses and dose rates most relevant to radiation therapy, tests of model equivalence indicate that an LQ formula with two first-order repair terms is an excellent approximation to the TLK model. We find the LQ and TLK models useful complementary tools for the analysis and prediction of radiobiological effects.

Animals↗
PubMed2002

Does increasing age have a negative impact on six-month functional outcome after coronary artery bypass?

BACKGROUND: Advances in medical care and improvements in catheter-based interventions for coronary artery disease have advanced the age at which patients present for coronary artery bypass graft (CABG) operations. The impact of age on functional outcome after CABG is unclear. METHODS: Functional outcome was assessed at baseline and at 6 months using the Duke Activity Status Index (DASI) in 337 consecutive patients undergoing primary or redo CABG. Complete functional outcome data were available in 292 patients (86%). RESULTS: The mean baseline DASI score was significantly lower in patients > or = 70 years of age (24.8 +/- 14.5 vs 30.9 +/- 17.8, P =.002) and at 6 months (29.6 +/- 16.5 vs 38.0 +/- 17.1, P =.0001); however, the 6-month change in DASI score (7.2 +/- 17.5 in patients < 70 years of age vs 4.9 +/- 14.0 in patients > or = 70 years of age, P =.23) was comparable. When examined in terciles of age, the 6-month change in DASI score was not significantly different (P =.11) in patients aged 31 to 60 years (5.8 +/- 18.0), aged 61 to 71 years (8.7 +/- 15.7), or aged 72 to 91 years (4.0 +/- 14.6). CONCLUSIONS: These functional outcome results demonstrate that older patients present for CABG at a significantly lower functional level and remain at a significantly lower functional level 6 months after CABG. However, the functional improvement after CABG is not significantly different across age groups.

Activities of Daily Living↗
PubMed2002

Daily dosing versus alternate-day dosing of simvastatin in patients with hypercholesterolemia.

STUDY OBJECTIVE: To compare the efficacy of daily simvastatin administration with that of alternate-day therapy at double the daily dose. DESIGN: Nonrandomized, before-after comparison trial. SETTING: Outpatient clinic of a Veterans Affairs medical center. PATIENTS: Fifteen men with hyperlipidemia. INTERVENTION: The simvastatin regimen for patients with a low-density lipoprotein cholesterol (LDL) level at their established National Cholesterol Education Program goal was converted from daily dosing to double the daily dose given every other day for 8 weeks. MEASUREMENTS AND MAIN RESULTS: Baseline laboratory values were obtained for patients receiving daily simvastatin therapy After 8 weeks of alternate-day therapy, follow-up laboratory values were obtained and assessed for efficacy and toxicity. The LDL-lowering effect of the daily dosing regimen was compared with that of the alternate-day dosing regimen. Paired t tests were computed to compare LDL concentrations before and after the study using a 95% confidence interval. No statistically significant difference was observed. CONCLUSION: Alternate-day dosing of simvastatin may be an effective alternative to daily dosing.

Aged↗