Milwaukee VA Medical Center

PURPOSE: Promising results from new approaches such as radiosurgery or stereotactic surgery of brain metastases have recently been reported. Are these results due to the therapy alone or can the results be attributed in part to patient selection? An analysis of tumor/patient characteristics and treatment variables in previous Radiation Therapy Oncology Group (RTOG) brain metastases studies was considered necessary to fully evaluate the benefit of these new interventions. METHODS AND MATERIALS: The database included 1200 patients from three consecutive RTOG trials conducted between 1979 and 1993, which tested several different dose fractionation schemes and radiation sensitizers. Using recursive partitioning analysis (RPA), a statistical methodology which creates a regression tree according to prognostic significance, eighteen pretreatment characteristics and three treatment-related variables were analyzed. RESULTS: According to the RPA tree the best survival (median: 7.1 months) was observed in patients < 65 years of age with a Karnofsky Performance Status (KPS) of at least 70, and a controlled primary tumor with the brain the only site of metastases. The worst survival (median: 2.3 months) was seen in patients with a KPS less than 70. All other patients had relatively minor differences in observed survival, with a median of 4.2 months. CONCLUSIONS: Based on this analysis, we suggest the following three classes: Class 1: patients with KPS > or = 70, < 65 years of age with controlled primary and no extracranial metastases; Class 3: KPS < 70; Class 2- all others. Using these classes or stages, new treatment techniques can be tested on homogeneous patient groups.

Measures of postural steadiness are used to characterize the dynamics of the postural control system associated with maintaining balance during quiet standing. The objective of this study was to evaluate the relative sensitivity of center-of-pressure (COP)-based measures to changes in postural steadiness related to age. A variety of time and frequency domain measures of postural steadiness were compared between a group of twenty healthy young adults (21-35 years) and a group of twenty healthy elderly adults (66-70 years) under both eyes-open and eyes-closed conditions. The measures that identified differences between the eyes-open and eyes-closed conditions in the young adult group were different than those that identified differences between the eye conditions in the elderly adult group. Mean velocity of the COP was the only measure that identified age-related changes in both eye conditions, and differences between eye conditions in both groups. The results of this study will be useful to researchers and clinicians using COP-based measures to evaluate postural steadiness.

IMPORTANCE: The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain. OBJECTIVE: To evaluate the effects of intensive (<120 mm Hg) compared with standard (<140 mm Hg) SBP targets in persons aged 75 years or older with hypertension but without diabetes. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015. INTERVENTIONS: Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319). MAIN OUTCOMES AND MEASURES: The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome. RESULTS: Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]). CONCLUSIONS AND RELEVANCE: Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01206062.

BACKGROUND: It is unclear how many children and adolescents develop post-traumatic stress disorder (PTSD) after trauma. AIMS: To determine the incidence of PTSD in trauma-exposed children and adolescents as assessed with well-established diagnostic interviews and to examine potential moderators of the estimate. METHOD: A systematic literature search identified 72 peer-reviewed articles on 43 independent samples (n = 3563). Samples consisting only of participants seeking or receiving mental health treatment were excluded. Main analyses involved pooled incidence estimates and meta-analyses of variance. RESULTS: The overall rate of PTSD was 15.9% (95% CI 11.5-21.5), which varied according to the type of trauma and gender. Least at risk were boys exposed to non-interpersonal trauma (8.4%, 95% CI 4.7-14.5), whereas girls exposed to interpersonal trauma showed the highest rate (32.9%, 95% CI 19.8-49.3). No significant difference was found for the choice of assessment interview or the informant of the assessment. CONCLUSIONS: Research conducted with the best available assessment instruments shows that a significant minority of children and adolescents develop PTSD after trauma exposure, with those exposed to interpersonal trauma and girls at particular risk. The estimates provide a benchmark for DSM-5 and ICD-11.

BACKGROUND: Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue androgen concentrations. However, the effects of the two types of drugs have not been compared. METHODS: We compared the safety and efficacy of placebo, terazosin (10 mg daily), finasteride (5 mg daily), and the combination of both drugs in 1229 men with benign prostatic hyperplasia. American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year. RESULTS: The mean changes from base line in the symptom scores in the placebo, finasteride, terazosin, and combination-therapy groups at one year were decreases of 2.6, 3.2, 6.1, and 6.2 points, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). The mean changes at one year in the peak urinary-flow rates were increases of 1.4, 1.6, 2.7, and 3.2 ml per second, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). Finasteride had no more effect on either measure than placebo. In the placebo group, 1.6 percent of the men discontinued the study because of adverse effects, as did 4.8 to 7.8 percent of the men in the other three groups. CONCLUSIONS: In men with benign prostatic hyperplasia, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone.

BACKGROUND: Regionally advanced, surgically unresectable non-small-cell lung cancer represents a disease with an extremely poor prognosis. External-beam irradiation to the primary tumor and regional lymphatics is generally accepted as standard therapy. The use of more aggressive radiation regimens and the addition of cytotoxic chemotherapy to radiotherapy have yielded conflicting results. Recently, however, results from clinical trials using innovative irradiation delivery techniques or chemotherapy before irradiation have indicated that patients treated with protocols that incorporate these modifications may have higher survival rates than patients receiving standard radiation therapy. PURPOSE: On the basis of these results, the Radiation Therapy Oncology Group (RTOG)-Eastern Cooperative Oncology Group (ECOG) elected to conduct a phase III trial comparing the following regimens: 1) standard radiation therapy, 2) induction chemotherapy followed by standard radiation therapy, and 3) twice-daily radiation therapy. METHODS: Patients with surgically unresectable stage II, IIIA, or IIIB non-small-cell lung cancer were potential candidates. Staging was nonsurgical. Patients were required to have a Karnofsky performance status of 70 or more and weight loss less than 5% for 3 months prior to entry into the trial, to be older than 18 years of age, and to have no metastatic disease. Of the 490 patients registered in the trial, 452 were eligible. The disease in 95% of the patients was stage IIIA or IIIB. More than two thirds of the patients had a Karnofsky performance status of more than 80. Patients were randomly assigned to receive either 60 Gy of radiation therapy delivered at 2 Gy per fraction, 5 days a week, over a 6-week period (standard radiation therapy); induction chemotherapy consisting of cisplatin (100 mg/m2) on days 1 and 29 and 5 mg/m2 vinblastine per week for 5 consecutive weeks beginning on day 1 with cisplatin, followed by standard radiation therapy starting on day 50; or 69.6 Gy delivered at 1.2 Gy per fraction twice daily (hyperfractionated radiation therapy). RESULTS: Toxicity was acceptable, with four treatment-related deaths. Three patients subsequently died of chronic pulmonary complications. Compliance with protocol treatment was acceptable. One-year survival (%) and median survival (months) were as follows: standard radiation therapy--46%, 11.4 months; chemotherapy plus radiotherapy--60%, 13.8 months; and hyperfractionated radiation therapy--51%, 12.3 months. The chemotherapy plus radiotherapy arm was statistically superior to the other two treatment arms (logrank P = .03). CONCLUSIONS: In "good-risk" patients with surgically unresectable non-small-cell lung cancer, induction chemotherapy followed by irradiation was superior to hyperfractionated radiation therapy or standard radiation therapy alone, yielding a statistically significant short-term survival advantage.

OBJECTIVE: The purpose of the study was to investigate the incidence, predictors, morbidity, and mortality associated with postoperative atrial fibrillation (AF) and its impact on intensive care unit (ICU) and postoperative hospital stay in patients undergoing cardiac surgery in the Department of Veterans Affairs (VA). SUMMARY BACKGROUND DATA: Postoperative AF after open cardiac surgery is rather common. The etiology of this arrhythmia and factors responsible for its genesis are unclear, and its impact on postoperative surgical outcomes remains controversial. The purpose of this special substudy was to elucidate the incidence of postoperative AF and the factors associated with its development, as well as the impact of AF on surgical outcome. METHODS: The study population consisted of 3855 patients who underwent open cardiac surgery between September 1993 and December 1996 at 14 VA Medical Centers. Three hundred twenty-nine additional patients were excluded because of lack of complete data or presence of AF before surgery, and 3794 (98.4%) were male with a mean age of 63.7+/-9.6 years. Operations included coronary artery bypass grafting (CABG) (3126, 81%), CABG + AVR (aortic valve replacement) (228, 5.9%), CABG + MVR (mitral valve replacement) (35, 0.9%), AVR (231, 6%), MVR (41, 1.06%), CABG + others (95, 2.46%), and others (99, 2.5%). The incidence of postoperative AF was 29.6%. Multivariate logistic regression analysis of factors found significant on univariate analysis showed the following predictors of postoperative AF: preoperative patient risk predictors: advancing age (odds ratio [OR] 1.61, 95% confidence interval [CI] 1.48-1.75, p < 0.001), chronic obstructive pulmonary disease (OR 1.37, 95% CI 1.12-1.66, p < 0.001), use of digoxin within 2 weeks before surgery (OR 1.37, 95% CI 1.10-1.70, p < 0.003), low resting pulse rate <80 (OR 1.26, 95% CI 1.06-1.51, p < 0.009), high resting systolic blood pressure >120 (OR 1.19, 95% CI 1.02-1.40, p < 0.026), intraoperative process of care predictors: cardiac venting via right superior pulmonary vein (OR 1.42, 95% CI 1.21-1.67, p < 0.0001), mitral valve repair (OR 2.86, 95% CI 1.72-4.73, p < 0.0001) and replacement (OR 2.33, 95% CI 1.55-3.55, p < 0.0001), no use of topical ice slush (OR 1.29, 95% CI 1.10-1.49, p < 0.0009), and use of inotropic agents for greater than 30 minutes after termination of cardiopulmonary bypass (OR 1.36, 95% CI 1.16-1.59, p < 0.0001). Postoperative median ICU stay (3.6 days AF vs. 2 days no AF, p < 0.001) and hospital stay (10 days AF vs. 7 days no AF, p < 0.001) were higher in AF. Morbid events, hospital mortality, and 6-month mortality were significantly higher in AF (p < 0.001): ICU readmission 13% AF vs. 3.9% no AF, perioperative myocardial infarction 7.41 % AF vs. 3.36% no AF, persistent congestive heart failure 4.57% AF vs. 1.4% no AF, reintubation 10.59% AF vs. 2.47% no AF, stroke 5.26% AF vs. 2.44% no AF, hospital mortality 5.95% AF vs. 2.95% no AF, 6-month mortality 9.36% AF vs. 4.17% no AF. CONCLUSIONS: Atrial fibrillation after cardiac surgery occurs in approximately one third of patients and is associated with an increase in adverse events in all measurable outcomes of care and increases the use of hospital resources and, therefore, the cost of care. Strategies to reduce the incidence of AF after cardiac surgery should favorably affect surgical outcomes and reduce utilization of resources and thus lower cost of care.

Two hundred five patients with neck pain were evaluated clinically and roentgenographically for a minimum of 10 years after onset of symptoms. Seventy-nine percent had a decrease in pain, and 43% were free of pain; however, 32% had moderate or severe residual pain. Patients who had been injured and initially had severe pain were the most likely to have an unsatisfactory outcome; however, no other clinical features were of value in predicting the final result. The presence or severity of pain was not related to the presence of degenerative changes, the sagittal diameter of the spinal canal, the degree of cervical lordosis, or to any changes in these measurements over the evaluation period.

The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of &lt;120 mm Hg (intensive group; n =1330) or &lt;140 mm Hg (standard group; n =1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD ( P values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (−0.47 versus −0.32 ml/min per 1.73 m 2 per year; P &lt;0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP&lt;120 mm Hg compared with &lt;140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.

OBJECTIVE: To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy. METHODS: Two hundred twenty-one patients with PsA were recruited from 15 clinics, randomized (double-blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint pain/ tenderness and swelling scores and physician and patient global assessments. RESULTS: Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea. CONCLUSION: SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA.

Bullous pemphigoid (BP) and herpes gestationis (HG) are skin diseases characterized by subepidermal blisters and autoantibodies against two hemidesmosomal Ag, i.e., BP230 and BP180. Based on sequence analysis the BP180 Ag was predicted to be a transmembrane protein with a long extracellular collagenous domain. In the present investigation fusion proteins encompassing various segments of the BP180 Ag were expressed in a prokaryotic system and assayed by immunoblotting and immunoadsorption against a panel of BP, HG and control sera. One antigenic site, comprising 14 amino acids of the BP180 noncollagenous (NC) 16A domain, was shown to be recognized by 60% of BP sera and by 63% of HG sera tested. 73% (11/15) of BP sera and 100% (8/8) of HG sera reacted with at least one of three BP180 fusion proteins representing various portions of the NC16A domain. Immunoadsorption analysis identified this region of BP180 as an immunodominant site. Using an affinity purified rabbit antiserum raised against a recombinant form of BP180, this BP/HG autoantibody-reactive region was localized to the epidermal basal lamina immediately adjacent to the hemidesmosome. These findings confirmed the predicted type II transmembrane orientation of the BP180 Ag. Thus, the long, C-terminal collagenous domain of this basal keratinocyte protein projects into the basal lamina and may function as a site of interaction with an extracellular matrix component. It is proposed that autoantibodies directed against the well-defined antigenic site on the BP180 ectodomain may play an initiatory role in subepidermal blister formation in BP and HG patients.

Most exhaled water is produced as gaseous water vapor, which can be collected in cooled condensers. The presence of nonvolatile solutes in these condensates suggests that droplets of respiratory fluid (RF) have also been collected. However, calculation of RF solute concentrations from condensates requires estimation of the dilution of RF droplets by water vapor. We used condensate electrolyte concentrations to calculate the dilution of RF droplets in condensates from 20 normal subjects. The total ionic concentration (conductivity) was 497 plus minus 68 (mean plus minus SEM) muM. Of this, 229 plus minus 43 muM was NH(4)(+), but little NH(4)(+) was collected from subjects with tracheostomies, indicating oral formation. The Na+ concentration in condensate ([Na+](cond)) averaged 242 plus minus 43 muM. Large variations in [Na(+)](cond) correlated well with variations of K+ in condensate ([K+](cond)) and Cl-) in condensate ([Cl-](cond)), and were attributed to differences in respiratory droplet dilution. Dividing condensate values of ([Na+] + [K+] ) by those of plasma indicated that RF represented between 0.01% and 2.00% of condensate volumes. Calculated values for Na+, K+, Cl-, lactate, and protein in RF were [Na+](RF) = 91 +/- 8 mM, [K+](RF) = 60 +/- 11 mM, [Cl-](RF) = 102 +/- 17 mM, [lactate](RF) = 44 +/- 17 mM, and [protein](RF) = 7.63 +/- 1.82 g/dl, respectively.

CPPD disease (also called pseudogout) is common, especially among persons older than 60 years of age, but it is underrecognized and undertreated. This review summarizes the diagnosis and treatment of the acute and chronic forms of this crystal-induced arthritis.

Autoantibodies present in the sera of patients with bullous pemphigoid (BP) bind to the basement membrane zone of normal human skin and commonly recognize two epidermal proteins, the BP240 and BP180 antigens. Two BP antigen cDNA clones from a lambda gt11 human keratinocyte library have been identified on the basis of reactivity with a BP serum. The fusion protein (FP) produced by one clone immunoadsorbed autoantibodies, which specifically recognized the BP180 by antigen, showing no cross-reactivity with BP240 by immunoblot analysis. The FP produced by the second clone immunoadsorbed autoantibodies which specifically reacted with the BP240 epidermal antigen. Northern blot analysis demonstrated that the BP180 and BP240 antigens are encoded by distinct RNA transcripts with lengths of 6.0 and 8.5 kb, respectively. Immunoblot analysis of the BP180 lysogen extract identified a 135-kD FP which was recognized by 7 of 16 BP sera and 7 of 8 herpes gestationis sera. A rabbit antiserum prepared against the lysogenic BP180 FP specifically recognized the BP180 antigen from human epidermal extracts by immunoblotting, labeled the BMZ by indirect immunofluorescence, and bound to human epidermal hemidesmosomes by immuno-electron microscopy. These results indicate that the BP180 antigen recognized by BP and herpes gestationis autoantibodies is a unique hemidesmosomal polypeptide, distinguishable from the BP240 antigen.

Although each of the major lipoprotein fractions is composed of various subclasses that may differ in atherogenicity, the importance of this heterogeneity has been difficult to ascertain owing to the labor-intensive nature of subclass measurement methods. We have recently developed a procedure, using proton nuclear magnetic resonance (NMR) spectroscopy, to simultaneously quantify levels of subclasses of very low density (VLDL), low density (LDL), and high density (HDL) lipoproteins; subclass distributions determined with this method agree well with those derived by gradient gel electrophoresis. The objective of the current study of 158 men was to examine whether NMR-derived lipoprotein subclass levels improve the prediction of arteriographically documented coronary artery disease (CAD) when levels of lipids and lipoproteins are known. We found that a global measure of CAD severity was positively associated with levels of large VLDL and small HDL particles and inversely associated with intermediate size HDL particles; these associations were independent of age and standard lipid measurements. At comparable lipid and lipoprotein levels, for example, men with relatively high (higher than the median) levels of either small HDL or large VLDL particles were three to four times more likely to have extensive CAD than were the other men; the 27 men with high levels of both large VLDL and small HDL were 15 times more likely to have extensive CAD than were men with low levels. In contrast, adjustment for levels of triglycerides or HDL cholesterol greatly reduced the relation of small LDL particles to CAD. These findings suggest that large VLDL and small HDL particles may play important roles in the development of occlusive disease and that their measurement, which is not possible with routine lipid testing, may lead to more accurate risk assessment.

The purpose of this study was to determine the optimal ratio of calcium hydroxyapatite (HA) to beta tricalcium phosphate (beta TCP) in a biphasic porous calcium phosphate (BCP) ceramic for effective repair of periodontal osseous defects. Defects were surgically produced in beagle dogs and made chronic for 4 months to simulate periodontal disease. Mucoperiosteal periodontal flaps were reflected, followed by osseous defect debridement and root planing. Specially prepared ceramic with different HA/beta TCP ratios were implanted into the prepared defects. The sites were allowed to heal for 6 months, animals were euthanized, and site-blocks were removed for histological study. During the follow-up phase, scaling and polishing were done once a month, and standardized probing attachment levels were recorded pre- and 6-months postoperatively. The Duncan's multiple range test showed that all the treatments produced statistically significant higher gain in probing attachment levels than the control group (0HA/0 beta TCP) (P < 0.05). Among the 7 "active" treatment groups, 2 (65/35 and 85/15) had significantly higher gain in probing attachment levels than those in 3 groups (50/50, 100/0, and 0/100) (P < 0.05). Histologically, higher HA ratio (but not 100% HA) showed accelerated new bone formation and new attachment levels. Based on histological results, the 85HA/15 beta TCP ratio appears to demonstrate greater gain in attachment level and bone regeneration in the treatment of periodontal osseous defects.

CONTEXT: The Accreditation Council for Graduate Medical Education implemented mandatory work hour limitations in July 2003, partly out of concern for residents' well-being in the setting of sleep deprivation. These limitations are likely to also have an impact on other aspects of the lives of residents. OBJECTIVE: To summarize the literature regarding the effect of interventions to reduce resident work hours on residents' education and quality of life. DATA SOURCES: We searched the English-language literature about resident work hours from 1966 through April 2005 using MEDLINE, EMBASE, and Current Contents, supplemented with hand-search of additional journals, reference list review, and review of abstracts from national meetings. STUDY SELECTION: Studies were included that assessed a system change designed to counteract the effects of resident work hours, fatigue, or sleep deprivation; included an outcome directly related to residents; and were conducted in the United States. DATA EXTRACTION: For each included study, 2 investigators independently abstracted data related to study quality, subjects, interventions, and findings using a standard data abstraction form. DATA SYNTHESIS: Fifty-four articles met inclusion criteria. The interventions used to decrease resident work hours varied but included night and day float teams, extra cross-coverage, and physician extenders. Outcomes included measures of resident education (operative experience, test scores, satisfaction) and quality of residents' lives (amount of sleep, well-being). Interventions to reduce resident work hours resulted in mixed effects on both operative experience and on perceived educational quality but generally improved residents' quality of life. Many studies had major limitations in their design or conduct. CONCLUSIONS: Past interventions suggest that residents' quality of life may improve with work hour limitations, but interpretation of the outcomes of these studies is hampered by suboptimal study design and the use of nonvalidated instruments. The long-term impact of reducing resident work hours on education remains unknown. Current and future interventions should be evaluated with more rigorous methods and should investigate links between residents' quality of life and quality of patient care.

Deep brain stimulation (DBS) is a widely accepted therapy for medically refractory Parkinson's disease (PD). Both globus pallidus internus (GPi) and subthalamic nucleus (STN) stimulation are safe and effective in improving the symptoms of PD and reducing dyskinesias. STN DBS is the most commonly performed surgery for PD as compared to GPi DBS. Ventral intermediate nucleus (Vim) DBS is infrequently used as an alternative for tremor predominant PD patients. Patient selection is critical in achieving good outcomes. Differential diagnosis should be emphasized as well as neurological and nonneurological comorbidities. Good response to a levodopa challenge is an important predictor of favorable long-term outcomes. The DBS surgery is typically performed in an awake patient and involves stereotactic frame application, CT/MRI imaging, anatomical targeting, physiological confirmation, and implantation of the DBS lead and pulse generator. Anatomical targeting consists of direct visualization of the target in MR images, formula-derived coordinates based on the anterior and posterior commissures, and reformatted anatomical stereotactic atlases. Physiological verification is achieved most commonly via microelectrode recording followed by implantation of the DBS lead and intraoperative test stimulation to assess benefits and side effects. The various aspects of DBS surgery will be presented.

We previously showed that hydrogen peroxide (H2O2) contributes to flow-induced dilation in human coronary resistance arteries (HCRAs); however, the source of this H2O2 is not known. We hypothesized that the H2O2 is derived from superoxide (O2*-) generated by mitochondrial respiration. HCRAs were dissected from right atrial appendages obtained from patients during cardiac surgery and cannulated with micropipettes. H2O2-derived radicals and O2*- were detected by electron spin resonance (ESR) using BMPO as the spin trap and by histofluorescence using hydroethidine (HE, 5 micromol/L) and dichlorodihydrofluorescein (DCFH, 5 micromol/L). Diameter changes to increases in pressure gradients (20 and 100 cm H2O) were examined in the absence and the presence of rotenone (1 micromol/L), myxothiazol (100 nmol/L), cyanide (1 micromol/L), mitochondrial complex I, III, and IV inhibitors, respectively, and apocynin (3 mmol/L), a NADPH oxidase inhibitor. At a pressure gradient of 100 cm H2O, ubisemiquinone and hydroxyl radicals were detected from effluents of vessels. Including superoxide dismutase and catalase in the perfusate reduced the ESR signals. Relative ethidium and DCFH fluorescence intensities in HCRAs exposed to flow were enhanced (1.45+/-0.15 and 1.57+/-0.12, respectively compared with no-flow) and were inhibited by rotenone (0.87+/-0.17 and 0.95+/-0.07). Videomicroscopic studies showed that rotenone and myxothiazol blocked flow-induced dilation (% max. dilation at 100 cm H2O: rotenone, 74+/-3% versus 3+/-13%; myxothiazol, 67+/-3% versus 28+/-4%; P<0.05). Neither cyanide nor apocynin altered flow-induced dilation. These results suggest that shear stress induced H2O2 formation, and flow-induced dilation is derived from O2*- originating from mitochondrial respiration.

The authors' objective was to review previous studies of immediate (first 30 seconds) and stabilized (30 seconds to 20 minutes) hemodynamic responses of healthy adults to the head-up posture, with particular reference to alteration of such responses in the elderly and the usefulness of such data in the diagnosis of orthostatic hypotension. The immediate response in healthy young adults is characterized by a prompt rise in heart rate, which peaks at about 8 to 15 seconds and then tapers; the arterial pressure and total vascular resistance decrease sharply at 5 to 10 seconds, followed by a rapid rebound and overshoot. Over the first 30 seconds there is a steady parallel decline of thoracic blood volume and stroke volume; there is also an initial surge of cardiac output followed by a steady decrease. During the stabilized response (30 seconds to 20 minutes), the hemodynamic variables are relatively steady, showing average increases in heart rate of about 15 to 30%, in diastolic pressure of 10 to 15%, and in total vascular resistance of 30 to 40%; during the 5th to 20th minutes there are also decreases in thoracic blood volume averaging about 25 to 30%, in cardiac output 15 to 30%, and in pulse pressure about 5 to 10%. It is evident that in normal human subjects, assumption of the upright posture results in profound hemodynamic changes, most of them occurring during the first 30 seconds. In elderly subjects (aged 60-69 years), there are, in the upright posture, lesser increments of heart rate and diastolic pressure, but no significant differences from younger age groups in the response of thoracic blood volume, cardiac output or total vascular resistance. However, beginning at about age 75, there is an increasing incidence of orthostatic hypotension, which averages about 14 to 20% at age 75 and older. The tendency toward orthostatic hypotension in the elderly is due (1) to the structural and functional changes in the circulation itself, (2) to a decline in autonomic function, and (3) to a probable functional deficiency of the skeletal muscle pump. The authors believe that closer hemodynamic monitoring of orthostatic hypotension patients would considerably increase our understanding and aid in the diagnosis of this condition.