University Hospital

To develop criteria for the classification of fibromyalgia, we studied 558 consecutive patients: 293 patients with fibromyalgia and 265 control patients. Interviews and examinations were performed by trained, blinded assessors. Control patients for the group with primary fibromyalgia were matched for age and sex, and limited to patients with disorders that could be confused with primary fibromyalgia. Control patients for the group with secondary-concomitant fibromyalgia were matched for age, sex, and concomitant rheumatic disorders. Widespread pain (axial plus upper and lower segment plus left- and right-sided pain) was found in 97.6% of all patients with fibromyalgia and in 69.1% of all control patients. The combination of widespread pain and mild or greater tenderness in greater than or equal to 11 of 18 tender point sites yielded a sensitivity of 88.4% and a specificity of 81.1%. Primary fibromyalgia patients and secondary-concomitant fibromyalgia patients did not differ statistically in any major study variable, and the criteria performed equally well in patients with and those without concomitant rheumatic conditions. The newly proposed criteria for the classification of fibromyalgia are 1) widespread pain in combination with 2) tenderness at 11 or more of the 18 specific tender point sites. No exclusions are made for the presence of concomitant radiographic or laboratory abnormalities. At the diagnostic or classification level, the distinction between primary fibromyalgia and secondary-concomitant fibromyalgia (as defined in the text) is abandoned.

BACKGROUND: Patients with heart failure who receive an implantable cardioverter-defibrillator (ICD) for primary prevention (i.e., prevention of a first life-threatening arrhythmic event) may later receive therapeutic shocks from the ICD. Information about long-term prognosis after ICD therapy in such patients is limited. METHODS: Of 829 patients with heart failure who were randomly assigned to ICD therapy, we implanted the ICD in 811. ICD shocks that followed the onset of ventricular tachycardia or ventricular fibrillation were considered to be appropriate. All other ICD shocks were considered to be inappropriate. RESULTS: Over a median follow-up period of 45.5 months, 269 patients (33.2%) received at least one ICD shock, with 128 patients receiving only appropriate shocks, 87 receiving only inappropriate shocks, and 54 receiving both types of shock. In a Cox proportional-hazards model adjusted for baseline prognostic factors, an appropriate ICD shock, as compared with no appropriate shock, was associated with a significant increase in the subsequent risk of death from all causes (hazard ratio, 5.68; 95% confidence interval [CI], 3.97 to 8.12; P<0.001). An inappropriate ICD shock, as compared with no inappropriate shock, was also associated with a significant increase in the risk of death (hazard ratio, 1.98; 95% CI, 1.29 to 3.05; P=0.002). For patients who survived longer than 24 hours after an appropriate ICD shock, the risk of death remained elevated (hazard ratio, 2.99; 95% CI, 2.04 to 4.37; P<0.001). The most common cause of death among patients who received any ICD shock was progressive heart failure. CONCLUSIONS: Among patients with heart failure in whom an ICD is implanted for primary prevention, those who receive shocks for any arrhythmia have a substantially higher risk of death than similar patients who do not receive such shocks.

Abstract Dual functional brain asymmetry refers to the notion that in most individuals the left cerebral hemisphere is specialized for language functions, whereas the right cerebral hemisphere is more important than the left for the perception, construction, and recall of stimuli that are difficult to verbalize. In the last twenty years there have been scattered reports of sex differences in degree of hemispheric specialization. This review provides a critical framework within which two related topics are discussed: Do meaningful sex differences in verbal or spatial cerebral lateralization exist? and, if so, Is the brain of one sex more symmetrically organized than the other? Data gathered on right-handed adults are examined from clinical studies of patients with unilateral brain lesions; from dichotic listening, tachistoscopic, and sensorimotor studies of functional asymmetries in non-brain-damaged subjects; from anatomical and electrophysiological investigations, as well as from the developmental literature. Retrospective and descriptive findings predominate over prospective and experimental methodologies. Nevertheless, there is an impressive accummulation of evidence suggesting that the male brain may be more asymmetrically organized than the female brain, both for verbal and nonverbal functions. These trends are rarely found in childhood but are often significant in the mature organism.

BACKGROUND: Dual-chamber (atrioventricular) and single-chamber (ventricular) pacing are alternative treatment approaches for sinus-node dysfunction that causes clinically significant bradycardia. However, it is unknown which type of pacing results in the better outcome. METHODS: We randomly assigned a total of 2010 patients with sinus-node dysfunction to dual-chamber pacing (1014 patients) or ventricular pacing (996 patients) and followed them for a median of 33.1 months. The primary end point was death from any cause or nonfatal stroke. Secondary end points included the composite of death, stroke, or hospitalization for heart failure; atrial fibrillation; heart-failure score; the pacemaker syndrome; and the quality of life. RESULTS: The incidence of the primary end point did not differ significantly between the dual-chamber group (21.5 percent) and the ventricular-paced group (23.0 percent, P=0.48). In patients assigned to dual-chamber pacing, the risk of atrial fibrillation was lower (hazard ratio, 0.79; 95 percent confidence interval, 0.66 to 0.94; P=0.008), and heart-failure scores were better (P<0.001). The differences in the rates of hospitalization for heart failure and of death, stroke, or hospitalization for heart failure were not significant in unadjusted analyses but became marginally significant in adjusted analyses. Dual-chamber pacing resulted in a small but measurable increase in the quality of life, as compared with ventricular pacing. CONCLUSIONS: In sinus-node dysfunction, dual-chamber pacing does not improve stroke-free survival, as compared with ventricular pacing. However, dual-chamber pacing reduces the risk of atrial fibrillation, reduces signs and symptoms of heart failure, and slightly improves the quality of life. Overall, dual-chamber pacing offers significant improvement as compared with ventricular pacing.

BACKGROUND: The mainstay of treatment for atrial fibrillation (AF) remains pharmacological; however, catheter ablation has increasingly been used over the last decade. The relative merits of each strategy have not been extensively studied. METHODS AND RESULTS: We conducted a randomized multicenter comparison of these 2 treatment strategies in patients with paroxysmal AF resistant to at least 1 antiarrhythmic drug. The primary end point was absence of recurrent AF between months 3 and 12, absence of recurrent AF after up to 3 ablation procedures, or changes in antiarrhythmic drugs during the first 3 months. Ablation consisted of pulmonary vein isolation in all cases, whereas additional extrapulmonary vein lesions were at the discretion of the physician. Crossover was permitted at 3 months in case of failure. Echocardiographic data, symptom score, exercise capacity, quality of life, and AF burden were evaluated at 3, 6, and 12 months by the supervising committee. Of 149 eligible patients, 112 (18 women [16%]; age, 51.1+/-11.1 years) were enrolled and randomized to ablation (n=53) or "new" antiarrhythmic drugs alone or in combination (n=59). Crossover from the antiarrhythmic drugs and ablation groups occurred in 37 (63%) and 5 patients (9%), respectively (P=0.0001). At the 1-year follow-up, 13 of 55 patients (23%) and 46 of 52 patients (89%) had no recurrence of AF in the antiarrhythmic drug and ablation groups, respectively (P<0.0001). Symptom score, exercise capacity, and quality of life were significantly higher in the ablation group. CONCLUSIONS: This randomized multicenter study demonstrates the superiority of catheter ablation over antiarrhythmic drugs in patients with AF with regard to maintenance of sinus rhythm and improvement in symptoms, exercise capacity, and quality of life.

BACKGROUND: Cerebral deoxygenation is associated with various adverse systemic outcomes. We hypothesized, by using the brain as an index organ, that interventions to improve cerebral oxygenation would have systemic benefits in cardiac surgical patients. METHODS: Two-hundred coronary artery bypass patients were randomized to either intraoperative cerebral regional oxygen saturation (rSO2) monitoring with active display and treatment intervention protocol (intervention, n = 100), or underwent blinded rSO2 monitoring (control, n = 100). Predefined clinical outcomes were assessed by a blinded observer. RESULTS: Significantly more patients in the control group demonstrated prolonged cerebral desaturation (P = 0.014) and longer duration in the intensive care unit (P = 0.029) versus intervention patients. There was no difference in overall incidence of adverse complications, but significantly more control patients had major organ morbidity or mortality (death, ventilation >48 h, stroke, myocardial infarction, return for re-exploration) versus intervention group patients (P = 0.048). Patients experiencing major organ morbidity or mortality had lower baseline and mean rSO2, more cerebral desaturations and longer lengths of stay in the intensive care unit and postoperative hospitalization, than patients without such complications. There was a significant (r(2) = 0.29) inverse correlation between intraoperative rSO2 and duration of postoperative hospitalization in patients requiring > or =10 days postoperative length of stay. CONCLUSION: Monitoring cerebral rSO2 in coronary artery bypass patients avoids profound cerebral desaturation and is associated with significantly fewer incidences of major organ dysfunction.

BACKGROUND: Some current pacing systems can automatically detect and record atrial tachyarrhythmias that may be asymptomatic. We prospectively studied a 312-patient (pt) subgroup of MOST (MOde Selection Trial), a 2010-patient, 6-year randomized trial of DDDR versus VVIR pacing in sinus node dysfunction (SND). The purpose of the study was to correlate atrial high rate events (AHREs) detected by pacemaker diagnostics with clinical outcomes. METHODS AND RESULTS: Pacemakers were programmed to log an AHRE when the atrial rate was >220 bpm for 10 consecutive beats. Analysis was confined to patients with at least 1 AHRE duration exceeding 5 minutes. The 312 patients were median age 74 years, 55% female, and 60% had a history of SVT. 160 of 312 (51.3%) patients enrolled had at least 1 AHRE >5 minutes duration over median follow-up of 27 months. Cox proportional hazards analysis assessed the relationship of AHREs with clinical events, adjusting for prognostic variables and baseline covariates. The presence of any AHRE was an independent predictor of the following: total mortality (hazard ratio AHRE versus no AHRE and 95% confidence intervals=2.48 [1.25, 4.91], P=0.0092); death or nonfatal stroke (2.79 [1.51, 5.15], P=0.0011); and atrial fibrillation (5.93 [2.88, 12.2], P=0.0001). There was no significant effect of pacing mode on the presence or absence of AHREs. CONCLUSIONS: AHRE detected by pacemakers in patients with SND identify patients that are more than twice as likely to die or have a stroke, and 6 times as likely to develop atrial fibrillation as similar patients without AHRE.

OBJECTIVE: To determine the incidence of radiographic knee osteoarthritis (OA) and symptomatic OA (symptoms plus radiographic OA), as well as the rate of progression of preexisting radiographic OA in a population-based sample of elderly persons. METHODS: Framingham Osteoarthritis Study subjects who had knee radiographs and had answered questions about knee symptoms in 1983-1985 were reexamined in 1992-1993 (mean 8.1-year interval) using the same protocol. Subjects were defined as having new (incident) radiographic OA if they developed grade > or = 2 OA (at least definite osteophytes or definite joint space narrowing). New symptomatic OA was present if subjects developed a combination of knee symptoms and grade > or = 2 OA. Progressive OA was diagnosed when radiographs showing grade 2 disease at baseline showed grade > or = 3 disease on followup. RESULTS: Of 1,438 participants in the original study, 387 (26.9%) died prior to followup. Of the 1,051 surviving subjects, 869 (82.7%) participated in the followup study (mean +/- SD age 70.8 +/- 5.0 at baseline). Rates of incident disease were 1.7 times higher in women than in men (95% confidence interval [CI] 1.0-2.7), and progressive disease occurred slightly more often in women (relative risk = 1.4; 95% CI 0.8-2.5) but rates did not vary by age in this sample. Among women, approximately 2% per year developed incident radiographic disease, 1% per year developed symptomatic knee OA, and about 4% per year experienced progressive knee OA. CONCLUSION: In elderly persons, the new onset of knee OA is frequent and is more common in women than men. However, among the elderly, age may not affect new disease occurrence or progression.

The effect of total hip replacement on the health-related quality of life of patients who have osteoarthrosis was examined as part of a randomized, controlled trial comparing femoral head prostheses that were inserted with or without cement. One hundred and eighty-eight patients were followed for three months: 179 of them, for six months; 156, for one year; and ninety, for two years. The health-related quality of life was assessed with use of the Harris hip score, the Merle d'Aubigné hip score, the Sickness Impact Profile, the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index, the McMaster--Toronto Arthritis (MACTAR) Patient Preference Disability Questionnaire, and the time trade-off technique as a measure of utility. Patients also took the six-minute-walk test. The mean age of the patients in the study was sixty-four years (range, forty to seventy-five years); ninety-seven patients (53 per cent) were men and ninety-four (50 per cent) had a prosthesis inserted with cement. Only three of 188 patients refused to return for quality-of-life assessments. There was significant improvement in all health-related quality-of-life measures and in the six-minute-walk test after the operation (p < 0.01 for all items, except for the work dimension of the Sickness Impact Profile at three months [p = 0.07]). Most of the improvement had occurred by three months postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

POUCHOT, JACQUES; SAMPALIS, JOHN S.; BEAUDET, FRANÇOIS; CARETTE, SIMON; DÉCARY, FRANCINE; SALUSINSKY-STERNBACH, MARION; HILL, ROSS O.; GUTKOWSKI, ANDRZEJ; HARTH, MANFRED; MYHAL, DANIEL; SENÉCAL, JEAN-LUC; YEADON, CAROL; ESDAILE, JOHN M. Author Information

PURPOSE: To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m 2 , day 1), ifosfamide (1.5 g/m 2 , days 1 to 3) and cisplatin (30 mg/m 2 , days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy. RESULTS: Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P = .38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P = .15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P = .027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P = .044). Disease-free survival time was significantly longer in the PCT arm (P = .033). CONCLUSION: Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.

Type I diabetes may be an autoimmune disorder, although the evidence is largely circumstantial. The natural history of the disease after diagnosis includes partial remission in most patients, but only about 3 percent achieve transient insulin independence. beta Cell function, as indicated by the plasma concentration of C-peptide, is lost over 6 to 30 months and islet cell antibodies disappeared over 1 to 2 years. This article describes a pilot study in which 41 patients were treated with the immunosuppressive agent cyclosporine for 2 to 12 months. Of 30 patients treated within 6 weeks of diagnosis, 16 became insulin independent with concentrations of plasma C-peptide in the normal range and decreasing titers of islet cell antibodies. Of 11 patients who entered the study 8 to 44 weeks after diagnosis, two achieved this state. These results indicate that a controlled trial of the effects of cyclosporine in type I diabetes should be conducted.

AIMS: To determine the effect of the glucagon-like peptide-1 analogue liraglutide on left ventricular function in chronic heart failure patients with and without type 2 diabetes. METHODS AND RESULTS: LIVE was an investigator-initiated, randomised, double-blinded, placebo-controlled multicentre trial. Patients (n = 241) with reduced left ventricular ejection fraction (LVEF ≤45%) were recruited (February 2012 to August 2015). Patients were clinically stable and on optimal heart failure treatment. Intervention was liraglutide 1.8 mg once daily or matching placebo for 24 weeks. The LVEF was similar at baseline in the liraglutide and the placebo group (33.7 ± 7.6% vs. 35.4 ± 9.4%). Change in LVEF did not differ between the liraglutide and the placebo group; mean difference (95% confidence interval) was -0.8% (-2.1, 0.5; P = 0.24). Heart rate increased with liraglutide [mean difference: 7 b.p.m. (5, 9), P < 0.0001]. Serious cardiac events were seen in 12 (10%) patients treated with liraglutide compared with 3 (3%) patients in the placebo group (P = 0.04). CONCLUSION: Liraglutide did not affect left ventricular systolic function compared with placebo in stable chronic heart failure patients with and without diabetes. Treatment with liraglutide was associated with an increase in heart rate and more serious cardiac adverse events, and this raises some concern with respect to the use of liraglutide in patients with chronic heart failure and reduced left ventricular function. More data on the safety of liraglutide in different subgroups of heart failure patients are needed.

COOK, DEBORAH J.; FULLER, HUGH D.; MARSHALL, JOHN C.; LEASA, DAVID; HALL, RICHARD; WINTON, TIMOTHY; RUTLEDGE, FRANK; TODD, THOMAS J. R.; ROY, PETER; LACROIX, JACQUES; GIFFITH, LAUREN; WILLAN, ANDREW Author Information

Clinical events following cerebral angiography were prospectively evaluated in 1,002 procedures. The ischemic event rate between 0 and 24 hours was 1.3% (0.1% permanent). This incidence was higher (2.5%) in patients investigated for cerebrovascular disease, but the difference was not significant. In addition, 1.8% of the patients suffered ischemia (0.3% permanent) between 24 and 72 hours after angiography. Cerebral ischemic events occurred as a recurrence or worsening of a preexisting phenomenon. twice as often as de novo. All permanent ischemia was a worsening of a preexisting phenomenon. There was a significant increase in the incidence of neurologic events between 0 and 24 hours when the procedure lasted longer than 60 minutes and when there was systolic hypertension. Trends toward higher incidence were noted with the use of increased volume of contrast, with increased serum creatinine, when transient ischemic attacks or stroke were the indications, and when 3 or more catheters were used. The incidence of neurologic events between 24 and 72 hours increased significantly with the increase in the amount of contrast used, with age, and with diabetes. The occurrence of nonneurologic events (mostly hematomas) was significantly increased by multiple factors. This study shows that events can and do occur beyond the usual observation period of 24 hours but confirms the low risk of cerebral angiography when performed judiciously.

The prevalence, characterization, and classification of acute, post-traumatic, occult subcortical fractures of the knee, identified at magnetic resonance (MR) imaging, were evaluated prospectively in 120 consecutive patients first seen with acute posttraumatic hemarthrosis of the knee. Occult subcortical femoral and tibial fractures were identified in 72% of patients. A modified MR imaging classification is suggested based on a combination of the appearances of such lesions at MR imaging and their short-term osteochondral sequelae. Among 67% of a cohort of 21 patients first seen with what have been described as occult geographic subcortical fractures, osteochondral sequelae were seen at follow-up MR imaging 6-12 months later. The evidence from this study indicates that specific subcategories of occult subcortical knee fractures are associated with an inordinately high prevalence of osteochondral sequelae, especially significant cartilage damage.

The literature is divided as to the necessity of an intact posterior cruciate ligament for functional stability. Presented here is a prospective study of isolated posterior cruciate injuries seen in the acute stage in 13 patients, 6 males and 7 females. The diagnosis of posterior cruciate ligament tear was made clinically and confirmed by arthroscopy. The average age at injury was 22 years. The athletic activity at injury was varied. Hyperflexion was the most common mechanism of injury, followed by pretibial trauma in the hyperflexed knee or in the "dashboard" injury. There were seven complete midsubstance tears and five partial tears. Direct visualization of the posterior cruciate ligament was not attained in one patient. All patients were treated nonoperatively on a physiotherapy routine. Average followup was 2.6 years. Patients were clinically examined and subjected to KT-1000 and Cybex testing. All patients were able to return to their previous activity and experienced no limitations with their injured knees. Using Hughston's criteria, subjective and functional ratings were all good. However, only 3 rated good and 10 fair when assessed objectively. We conclude that acceptable functional stability in these patients does not necessarily require absolute static stability. Nonoperative treatment of the isolated posterior cruciate ligament midsubstance injury may be a viable alternative to the difficult repair/reconstruction procedure.

The Intergroupe Francophone du Myélome (IFM) initiated 2 trials in 1999 to study patients with high-risk (β2-microglobulin level greater than 3 mg/L and chromosome 13 deletion at diagnosis) de novo multiple myeloma. In both protocols, the induction regimen consisted of vincristine, doxorubicin, and dexamethasone (VAD) followed by first autologous stem cell transplantation (ASCT) prepared by melphalan 200 mg/m2. Patients with an HLA-identical sibling donor were subsequently treated with dose-reduced allogeneic stem cell transplantation (IFM99-03 trial), and patients without an HLA-identical sibling donor were randomly assigned to undergo second ASCT prepared by melphalan 220 mg/m2 and 160 mg dexamethasone with or without anti–IL-6 monoclonal antibody (IFM99-04 protocol). Two hundred eighty-four patients—65 in the IFM99-03 trial and 219 in the IFM99-04 trial—were prospectively treated and received at least one course of VAD. On an intent-to-treat basis, overall survival (OS) and event-free survival (EFS) did not differ significantly in the studies (medians 35 and 25 months in the IFM99-03 trial vs 41 and 30 months in the IFM99-04 trial, respectively). With a median follow-up time of 24 months, the EFS of the 166 patients randomly assigned in the tandem ASCT protocol was similar to the EFS of the 46 patients who underwent the entire IFM99-03 program (median, 35 vs 31.7 months), with a trend for a better OS in patients treated with tandem ASCT (median, 47.2 vs 35 months; P = .07). In patients with high-risk de novo MM, the combination of ASCT followed by dose-reduced allogeneic transplantation was not superior to tandem dose–intensified, melphalan-based ASCT.

The hypervigilance model of pain perception states that chronic pain patients have a heightened sensitivity to pain (e.g. low threshold and tolerance) because of increased attention to external stimulation and a preoccupation with pain sensations. This study tested the hypothesis that individuals with fibromyalgia, a chronic pain disorder of undetermined origin, have a generalized hypervigilant pattern of responding that extends beyond the pain domain. Twenty fibromyalgia out-patients, 20 rheumatoid arthritis (RA) patients, and 20 normal controls served as subjects. The RA and normal control subjects were age and sex matched to the fibromyalgia patients. Subjects were tested for pain tolerance, pain threshold, and noise tolerance and were asked to complete a number of questionnaires that assessed hypervigilance. As predicted, the responses of the fibromyalgia patients to both the pain and auditory stimuli were consistent with the generalized hypervigilance hypothesis. These patients had significantly lower threshold and tolerance values than the RA patients, who in turn, had lower values than the normal control subjects. The results of the psychological questionnaires revealed that the fibromyalgia and RA patients preferred lower levels of external stimulation than the control subjects. The outcome of this study supports the generalized hypervigilance hypothesis, suggesting that fibromyalgia patients have a perceptual style of amplification. The implications of these findings for understanding the role of biological, cognitive, and perceptual factors in pain disorders are discussed.

Measurement of 133Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO2 at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml·100 g−1·min−1 and cerebral oxygen consumption, 1.67 ml·100 g−1·min−1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26°C was reduced to 0.42 ml·100 g−1·min−1 in both groups. CBF was reduced to 14–15 ml·100 g−1·min−1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20–100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml·100 g−1·min−1, and flow I metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15–95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermie non-pulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO2 of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption.