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The purpose of this study was to assess the effect of azimilide, a Class III antiarrhythmic drug, on ECG conduction intervals recorded during sinus rhythm in patients with a history of symptomatic atrial fibrillation or atrial flutter. In Phase I clinical pharmacology studies, azimilide was associated with prolongation of the QT and QTc intervals on electrocardiograms recorded during sinus rhythm in normal subjects, but the effect of azimilide on the target population of patients with atrial fibrillation has not been reported in detail previously. Patients with a history of atrial fibrillation, atrial flutter, or both were randomly assigned to receive placebo or azimilide twice daily for 3 days and then qd thereafter. Azimilide doses of 50 mg, 100 mg, or 125 mg were tested. The RR, PR, QRS, QT, QTc(Bazett), and QTc(Fridericia) intervals were measured from electrocardiograms recorded at baseline and on Day 4 of test therapy. Increasing azimilide doses were associated with significant increases in the RR, QT, QTc(Bazett), and QTc(Fridericia) compared with changes in the placebo group based on the F-test for differences among treatment groups and the test for a dose response. In the azimilide 125 mg dose group, the mean change in RR was significantlygreater than the mean change in the placebo group (+61.4 ms in the azimilide 125 mg group vs. -14.1 ms in the placebo group). The mean change in QT was significantly greater in the azimilide 125 mg group than the mean change in the placebo group (+44.2 ms in the azimilide 125 mg group vs. -1.0 ms in the placebo group). The mean change in QTc using both correction methods was significantly greater in the azimilide 125 mggroup than the mean change in the respective placebo group: QTc(Bazett) +31.6 ms in the azimilide 125 mg group versus +2.1 ms in the placebo group and QTc(Fridericia) +35.8 in the azimilide 125 mg group versus +1.0 ms in the placebo group. It was concluded that in patients with a history of atrial fibrillation or flutter, azimilide was associated with statistically significant increases in RR, QT, QTc(Bazett), and QTc(Fridericia) when patients were in sinus rhythm. [ABSTRACT FROM AUTHOR]

Background: A cardiac rehabilitation programme is a medically supervised intervention to assist patients in recovery after heart surgeries and to prevent potential complications. Nurses should have the knowledge, a positive attitudes, and good practices to improve patient quality of life during the recovery process., Aim: This study aimed to describe the knowledge, attitudes, and practices of the nurses regarding cardiac rehabilitation for patients after heart valve surgery., Setting: The study setting was Windhoek Central Hospital, Cardiac Unit, in Windhoek, Namibia., Methods: A quantitative and descriptive research design was used for convenient non-probability sampling of ( N = 23) nurses who consented to participate in the study. Data were collected through self-administered questionnaires and analyzed using SPSS Version 26. Descriptive statistics were used and Fischer's Exact test for associations of variables was performed., Results: The study results showed a high level of knowledge, good attitudes, and poor to fair practices toward cardiac rehabilitation. However, the respondents demonstrate a lack of knowledge about the indications, and benefits of cardiac rehabilitation, negative attitudes regarding counselling of patients on sexual activities, and poor practice regarding exercises and counseling of patients and caregivers on cardiac rehabilitation. Furthermore, there is a positive relationship between the respondents' older age, senior rank, and having been trained I cardiac conditions and their knowledge, attitudes and practices regarding some core components of cardiac rehabilitation with P-value < 0.050., Conclusion: There is a need for a cardiac rehabilitation programme to improve nurses' attitudes and practices toward cardiac rehabilitation., Contribution: Understanding the gap in knowledge, attitudes, and practices among the nurses regarding cardiac rehabilitation would guide the Ministry of Health and Social Services (MoHSS) in the implementation of the cardiac rehabilitation for patients after heart valve surgery., Competing Interests: The authors have declared that no competing interest exists., (© 2024. The Authors.)

Experts are believed to make fewer errors than novices. Researchers in other domains have shown that experts not only make less errors, they also detect and recover from these errors better than non-experts. To investigate this phenomenon among dialysis technicians working in hemodialysis, we evaluated the ability of dialysis technicians to detect and recover from healthcare errors. Two clinical cases with embedded errors were created by an expert nephrology nurse. Twenty-four dialysis technician subjects read the cases aloud and then answered a set of related questions. Subjects' error detection and recovery responses were scored against the clinical cases. We found that there was no significant difference between the ability of expert and non-expert dialysis technicians to detect errors. However, expert dialysis technicians recovered from significantly more healthcare errors than less experienced non-expert dialysis technicians. This has implications for training dialysis technicians in better error detection and recovery strategies.

Objectives: Our aim for this study was to evaluate dialysis nurses' ability to detect and recover from nursing errors., Methods: Two clinical cases with a total of 12 embedded errors were constructed. The errors were based on real events but were modified for the experimental design by an expert dialysis nurse. A total of 31 registered nurse subjects "talked aloud" as they read through the 2 cases and answered a set of predesigned knowledge-based and procedural questions. The talk-aloud sessions were recorded and transcribed for analysis of errors detected and recovered., Results: Performance on procedurally based error detection and recovery was significantly higher as a function of expertise (P < 0.05), where more-experienced nurses performed better than the less-experienced nurses in detecting and recovering procedurally based errors. However, no differences were found for knowledge-based errors., Conclusions: Expert nurses develop a special ability to detect and recover from nursing errors, but the nature of these errors depends on the nature of the task. Dialysis nursing requires more knowledge of procedures rather than conceptual knowledge in their routine work, and thus, the nurses develop better procedurally based skills. This raises concern about nurses making knowledge-based or conceptual errors, which, if made, are not detected or corrected. The need for understanding conceptual knowledge underlying procedures and for training in error detection and correction strategies is discussed in the context of nursing.

Introduction: Azimilide hydrochloride is an investigational antiarrhythmic medication that had shown evidence of efficacy in prolonging the time to recurrence of atrial fibrillation (AF) or atrial flutter (AFL) and paroxysmal supraventricular tachycardia (PSVT). This study was designed to confirm efficacy of 125 mg daily azimilide., Methods and Results: The primary endpoint was ECG-documented recurrence of AF, AFL, or PSVT, followed for a maximum of 180 days. Four hundred eighty-two patients were enrolled in the United States and Canada (422 with AF or AFL and 60 with PSVT). The primary efficacy analysis included 402 patients with AF-AFL and 56 patients with PSVT. There was no significant difference in the time to first recurrence of symptomatic supraventricular arrhythmia in the AF-AFL stratum (median of 38 days for azimilide versus 27 days for placebo; hazard ratio [HR] of 1.14, P = 0.29). Similarly, there was no difference in time to recurrence in the PSVT stratum (>180 days for azimilide versus 135 days for placebo; HR = 1.28, P = 0.55). There were three deaths in the azimilide group and one in the placebo group. Four patients had nonsustained ventricular tachycardia (one torsades de pointes), all in the azimilide group. Asymptomatic recurrence was frequent in the AF-AFL group (8% with azimilide and 11% with placebo), but was absent in the PSVT group. False recurrence was common in both groups., Conclusion: Azimilide 125 mg daily was not associated with significant prolongation of the time to recurrent symptomatic supraventricular arrhythmias. There was substantial discordance between symptoms and recurrence.

Azimilide hydrochloride (azimilide), an investigational antiarrhythmic drug, has shown variable efficacy in preventing atrial fibrillation (AF). This study was designed to assess its efficacy in maintaining sinus rhythm in patients with paroxysmal AF and heart disease. Patients with symptomatic paroxysmal AF were screened for 1 month by transtelephonic monitoring. After recording 1 episode of AF in the screening period, they were randomized to receive azimilide 125 mg or placebo once daily. Patients were stratified by the presence or absence of congestive heart failure or coronary heart disease (CHF/CHD). A maximum of 220 patients without CHF/CHD were randomized, with the remainder having CHF/CHD. Patients with CHF/CHD were monitored for 3 days during loading. The primary efficacy analysis was the time to the first symptomatic recurrence of AF in the CHF/CHD group. Secondary analyses were the time to the first recurrence in the entire population and the time to the first recurrence in those with significant structural heart disease. The median time to recurrence of AF in the CHF/CHD group was 10 days in the 2 treatment arms. Nonsignificant trends were seen toward efficacy of azimilide in the CHF/CHD group (hazard ratio 1.28, 95% confidence interval 0.97 to 1.70, p=0.087), structural heart disease group (hazard ratio 1.22, 95% confidence interval 0.96 to 1.56, p=0.11), and overall group (hazard ratio 1.22, 95% confidence interval 1.00 to 1.49, p=0.053). No patient died. In conclusion, azimilide showed a nonsignificant trend toward efficacy in maintaining sinus rhythm in patients with AF.

Background: Azimilide dihydrochloride (azimilide) is an investigational antiarrhythmic drug that has been tested in patients with a variety of arrhythmias. In patients with atrial fibrillation, it has shown excellent efficacy in some previous trials and minimal efficacy in others., Methods: Patients who had symptomatic atrial fibrillation for > 48 hours but < 6 months were eligible for this multicenter, randomized, placebo-controlled clinical trial. Patients were admitted to a hospital and randomly assigned to receive either azimilide 125 mg or a matched placebo twice daily for 3 days and then once daily. Patients who were in sinus rhythm spontaneously or had sinus rhythm restored by electric cardioversion on day 4 were discharged from the hospital. Recurrence of atrial fibrillation was documented by electrocardiogram. In the primary efficacy analysis, time to recurrence in the 2 treatment groups was compared with the log-rank test in the subgroup of patients with structural heart disease. Safety was assessed as deaths, adverse events, and serious adverse events., Results: A total of 446 patients were randomized in the study; 314 were in the subgroup with structural heart disease. The median time to arrhythmia recurrence in both treatment groups with structural heart disease was 13 days, and the difference between treatments was not significant (P = .4596, n = 314). The relative risk for recurrence (placebo:azimilide) was 1.104 (95% CI 0.849-1.436). There was 1 death in the placebo group and 3 in the azimilide group., Conclusions: Azimilide did not demonstrate clinically important or statistically significant efficacy in reducing the risk for arrhythmia recurrence in patients with structural heart disease who were in atrial fibrillation and converted to sinus rhythm.

Nitric oxide (NO) may play important roles in rheumatoid arthritis (RA). RA is an inflammatory disease involving joints and other systems including salivary glands. To assess NO production in RA patients, we compared levels of serum, urine, and salivary nitrite and nitrate (NOx) in patients with RA and normal subjects, and we examined the relationships of these measures to disease activity. Serum, urine, and NOx levels as well as renal creatinine, NOx clearance and fractional excretion rates were compared in 25 RA patients and 20 age- and gender-matched healthy controls. Subjects were hospitalized for 3 days and placed on a NOx restricted diet. NOx was assayed using nitrate reductase and the Griess reagent. RA activity was assessed using standard clinical and laboratory measures. While consuming a restricted diet for 3 days to eliminate the effects of oral intake of NOx, 24 hour urinary NOx excretion decreased in both RA patients and healthy controls. Urine NOx levels at all time points were not significantly different between RA patients and normal subjects. Serum NOx levels also decreased during the 3 days of NOx restriction, but RA patients had higher serum NOx levels at all time points compared with the control group. Likewise, serum NOx/creatinine ratios were higher in RA patients than in controls. Although basal salivary flow rate and tear flow were lower in RA patients, salivary NOx levels did not differ between normal and RA subjects. While renal creatinine clearance was not different between the two groups, we found that RA patients had lower renal NOx clearance and lower renal NOx fractional excretion. After correction of p values for multiple comparisons, there were no significant relationships for the RA group between measures of disease activity and the urinary NOx, serum NOx, or urinary NOx clearance. Despite interest in the use of NO as a marker of disease activity, alterations in renal NOx clearance and fractional excretion in RA make it difficult to assess in vivo NO production even with strict dietary restriction of NOx intake.

Background: Azimilide is a new antiarrhythmic agent being developed for the management for atrial fibrillation and flutter (AF). Four randomized, placebo-controlled, double-blind trials have been performed that investigated the effect of azimilide on time to first recurrence of symptomatic AF. This paper examines the data collected during those studies regarding the symptoms reported by patients at the time of AF recurrence, Methods: At the time that patients reported their first documented symptomatic recurrence of arrhythmia, they were systematically asked whether or not they were experiencing any of the following 6 symptoms: palpitation, fatigue, chest pain, shortness of breath, dizziness, or sweating. Patients were required to answer yes or no. A symptom score was created varying from 0 to 6, in increasing order of number of symptoms reported. This was compared for patients receiving either of 2 doses of azimilide or placebo. The relationship between the number of symptoms, heart rate at time of arrhythmia recurrence and treatment was analyzed., Results: In 2 separate studies, azimilide at a dose of 125 mg/day significantly reduced the number of symptoms at the time of arrhythmia recurrence compared to placebo. On the other hand, in 2 studies, the dose of 100 mg/day did not significantly reduce symptom burden. The individual symptoms significantly reduced by azimilide125 mg/day were fatigue, shortness of breath, chest pain and dizziness. Palpitations and sweating were not significantly reduced. Modeling of heart rate at the time of arrhythmia recurrence, symptoms and treatment indicated that a small reduction in heart rate with azimilide accounted for only a small part of the symptom reduction. There was another effect of azimilide: an average reduction of 0.38 symptoms (P <.01) that was independent of heart rate., Conclusion: Azimilide (125 mg/day) reduces the number of symptoms reported at the time of AF recurrence.

With the recent transition of the liver transplant allocation system to the Model for End-Stage Liver Disease, a major change is its reliance entirely on objective criteria. In previous reports, potential donor families and members of the transplant community have questioned the fairness of the subjective nature of previous systems. Therefore, we examined the United Network for Organ Sharing database to determine if the previous allocation system benefited a particular group in prioritization for transplant. We included adult patients with chronic liver disease listed for transplant in the year 2000. Patients who had ever been listed as status 2A or 2B were analyzed. A multivariable analysis examined the patient characteristics that predicted being uplisted to status 2A. Of the 9244 patients, 2376 (25.7%) had received a liver transplant as a status 2A or had been listed as status 2A. In the multivariate analysis, the strongest patient characteristics that predicted status 2A were listing in the western United States and shorter duration of registration. Other predictors include blood type O, college education, unemployment, and coverage with private insurance or a health maintenance organization/preferred provider organization. In addition, patients with Laennec's cirrhosis were less likely to be uplisted to status 2A. Age, gender, and race were not predictors of uplisting to status 2A. In conclusion, these data show the wide range of practice patterns with the use of status 2A, and these findings suggest that certain patient groups might have received preference in the previous liver transplant allocation system.

Objective: To investigate risk factors for positive minor salivary gland biopsy results in Sjögren's syndrome (SS) and dry mouth patients., Methods: A total of 289 patients with dry mouth symptoms were evaluated. Potential risk factors for positive minor salivary gland biopsy results (>1 focus of lymphocytes) were studied in 2 phases. In phase 1, predictor variable candidates were identified for the test study (phase 2). Odds ratios were calculated for predictor variables., Results: IgG, IgA, keratoconjunctivitis sicca, and sex, identified as the best predictor variables from phase 1 data, were included in a logistic regression model using phase 2 data. Only IgG demonstrated association with biopsy results (chi(2) = 20.4, P = 0.0001). An elevated IgG level (>1,482 mg/dl) had a high specificity (97% and 97%), high positive predictive value (PPV) (97% and 97%), but poor sensitivity (40% and 45%) in predicting positive biopsy results and SS, respectively., Conclusion: Elevated serum IgG levels best predicted a positive biopsy result and SS with high PPV and specificities.

Background: Azimilide is a novel classification III antiarrhythmic agent that blocks both I(Kr)and I(Ks)and shows evidence of efficacy in patients with atrial fibrillation or flutter. Its effect on paroxysmal supraventricular tachycardia (PSVT) has not been reported., Methods and Results: One hundred ninety-three patients with symptomatic PSVT were enrolled in 4 double-blind, randomized, placebo-controlled clinical trials with almost identical trial design (supraventricular arrhythmia-1 [SVA-1], SVA-2, SVA-3, and SVA-4), performed as a separate stratum of studies that also included a stratum of patients with atrial fibrillation or flutter. Patients received oral azimilide (100 mg in SVA-1 and SVA-3, 35 or 75 mg in SVA-2, and 125 mg in SVA-4) or matching placebo twice daily for 3 days (loading period), followed by once-daily dosing (maintenance period). The primary outcome variable was the first recording of a symptomatic supraventricular arrhythmia (either PSVT, atrial fibrillation, or atrial flutter) recorded on a transtelephonic electrocardiographic event recorder. The duration of study was 270 days in SVA-1 and SVA-2 and 180 days in SVA-3 and SVA-4. Combined analysis results of the PSVT stratum from the 4 studies showed a dose-response relationship in prolongation of time to recurrence (P =.02). In the combined 100-mg daily dose, the hazard ratio (placebo:azimilide) was 2.35 (P =.023). The hazard ratio for the 125-mg daily dose measured 1.28 (P = not significant). However, the time to recurrence was prolonged when the patients receiving 100 and 125 mg daily were combined and compared with placebo (P =.02). There were no deaths and 1 case of torsades de pointes., Conclusion: These trial results suggest a significant dose-related suppression of PSVT with azimilide, with a low risk of serious adverse events.

We evaluated the efficacy and safety of azimilide, a new class III antiarrhythmic agent that blocks both the slow and fast components of the cardiac-delayed rectifier potassium currents in 4 randomized, double-blind, placebo-controlled trials with similar protocols. The purpose of this study was to assess the relation between dose and effect. A total of 1,380 patients with a documented history of symptomatic atrial fibrillation (AF), atrial flutter, or both, were enrolled. After a 3-day loading period during which the assigned dose was given twice a day, subjects received placebo or azimilide (35, 50, 75, 100, or 125 mg once a day) for the duration of the study period. The primary end point of the studies was the time to symptomatic arrhythmia recurrence with a transtelephonic electrocardiogram typical of AF, atrial flutter, or paroxysmal supraventricular tachycardia. For each study, Kaplan-Meier estimates of the median time to recurrence were computed for placebo and for each azimilide dose. Cox proportional-hazards modeling was used to estimate hazard ratios for each active dose. Each of the 2 highest azimilide doses (100 and 125 mg/day) significantly prolonged the time to recurrence of arrhythmia. For the 100 mg/day dose, the hazard ratio was 1.34, 95% confidence interval 1.05 to 1.72; p = 0.02. For the 125 mg/day dose, the hazard ratio was 1.32, 95% confidence interval 1.07 to 1.62; p = 0.01. Patients with a history of either ischemic heart disease or congestive heart failure had a significantly greater treatment effect from azimilide than those without it. Torsades de Pointes occurred in 0.9% of patients receiving either of the 2 effective doses. Thus, doses of azimilide <100 mg/day are not effective for control of AF, whereas doses of 100 and 125 mg/day are effective with an acceptable risk of serious toxicity.

Objective: To determine the feasibility, safety, and potential clinical efficacy of intravenous (IV) doxycycline therapy for rheumatoid arthritis (RA), as well as its possible effects on serum and urinary markers of collagen breakdown., Methods: The exploratory trial was designed as a 16-week, single-center, randomized, double-blind, placebo-controlled trial. Eligible subjects with active seropositive or erosive RA were randomly allocated into 3 treatment groups: doxycycline 200 mg IV, azithromycin 250 mg orally, or placebo. The blinded IV study drug was administered once daily for the first 3 weeks by home self-infusion and then weekly for the next 8 weeks, concurrent with the blinded oral study drug at the prescribed doses. The primary end points were the change between baseline and week 4 in the tender joint count, erythrocyte sedimentation rate, and urinary excretion of pyridinoline., Results: The trial was stopped prematurely after enrollment of 31 patients. Three subjects were withdrawn because of worsening arthritis, and 1 patient was withdrawn when newly diagnosed with breast cancer. Infusion-related events occurred in 13 (42%) of 31 patients, but none were serious. There were 4 serious adverse events unrelated to the study drug, including a new diagnosis of breast cancer in 3 cases and hospitalization for abdominal pain in 1 case. No significant differences were observed across treatment groups in any of the 3 primary clinical end points., Conclusion: Although IV doxycycline therapy was generally well-tolerated by patients in this trial, it did not show any evidence of reducing disease activity or collagen crosslink production.

Objective: To determine if a visual intervention (medication grid) delivered to physicians can reduce medication regimen complexity., Design: Nonrandomized, controlled trial., Setting: Veterans Affairs medical center., Patients/participants: Eight hundred thirty-six patients taking at least 5 medications at the time of admission and the 48 teams of physicians and students on the general medicine inpatient service., Intervention: For intervention patients, a medication grid was created that displayed all of the patients' medicines and the times of administration for 1 week. This grid was delivered to the admitting resident soon after admission., Measurements and Main Results: For the patients of each team of physicians, we calculated the change in the average number of medications and doses from admission to discharge. The number of medications in the intervention group decreased by 0.92 per patient, and increased by 1.65 in the control group (P <.001). The mean number of doses per day in the intervention group decreased by 2.47 per patient and increased by 3.83 in the control group (P <.001)., Conclusions: This simple intervention had a significant impact on medication regimen complexity in this population. Apparently, physicians were able to address polypharmacy when the issue was brought to their attention.

Objectives: The purpose of this study was to assess the effectiveness of azimilide, a class III antiarrhythmic drug, in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation, atrial flutter or both., Background: Atrial fibrillation is an increasingly common disorder of the heart rhythm, and most patients with this problem are identified because they have symptoms associated with their arrhythmia. New antiarrhythmic therapies are needed to treat patients with this problem., Methods: A total of 384 patients with a history of atrial fibrillation, atrial flutter or both were randomly assigned to receive once daily doses of placebo or azimilide; recurrent symptomatic arrhythmias were documented using transtelephonic electrocardiogram (ECG) recording. Azimilide 50 mg, 100 mg or 125 mg was tested; the primary efficacy analysis compared the time to first symptomatic recurrence in the combined azimilide 100 mg and 125 mg dose groups with that in the placebo group using the log-rank test., Results: In the primary efficacy analysis, the time to first symptomatic arrhythmia recurrence was significantly prolonged in the combined azimilide 100 mg and 125 mg daily dose group compared with the placebo group (chi-square 7.96, p = 0.005); the hazard ratio (placebo: azimilide) for this comparison was 1.58 (95% confidence interval [CI] = 1.15, 2.16). In comparisons between individual doses and placebo, the hazard ratio for the 50 mg daily dose was 1.17 (95% CI = 0.83, 1.66; p = 0.37); for the 100 mg group, dose was 1.38 (95% CI = 0.96, 1.98; p = 0.08), and for the 125 mg group, dose was 1.83 (95% CI = 1.24, 2.70; p = 0.002)., Conclusions: Azimilide significantly lengthened the symptomatic arrhythmia-free interval in patients with a history of atrial fibrillation, atrial flutter or both.

Background: Quantitative data on the frequency with which transition from intermittent to permanent atrial fibrillation occurs are lacking. We conducted this study to determine the proportion of patients with intermittent atrial fibrillation who progress to permanent atrial fibrillation and to investigate baseline clinical characteristics that might predict such a progression., Methods: This retrospective cohort study included 231 patients who were seen with intermittent atrial fibrillation at a university hospital-based clinic from January 1978 through December 1997. Patients' medical records and electrocardiograms were reviewed and data were collected for all clinic visits through May 1998. The proportion of patients who remained free of transition from intermittent to permanent atrial fibrillation was calculated by the Kaplan-Meier method. A Cox proportional hazards model was used to determine the effect of some baseline characteristics on this transition., Results: The number of patients who remained free of transition from intermittent to permanent atrial fibrillation was 92% (95% confidence interval 88%-96%) at 1 year and 82% (95% confidence interval 75%-88%) at 4 years. Among 5 baseline characteristics (age, sex, structural heart disease, atrial fibrillation at presentation, and use of an antiarrhythmic medicine before presentation), the 2 significant predictors of progression from intermittent to permanent atrial fibrillation were age (P =.0003) and being in atrial fibrillation at presentation (P =.0006). The hazard ratio associated with 10 years of advancing age was 1.82 (95% confidence interval 1.31-2.51), and the hazard ratio associated with atrial fibrillation at presentation was 3.56 (95% confidence interval 1.73-7.34)., Conclusions: Approximately 18% of patients who had intermittent atrial fibrillation were permanently in atrial fibrillation after 4 years of follow-up. Age and being in atrial fibrillation at presentation were the only 2 important clinical variables identified in predicting such a progression.

The purpose of this study was to determine whether thymic transplantation in addition to highly active antiretroviral therapy (HAART) will restore T cell function in HIV infection. Eight treatment-naive HIV-infected patients with CD4+ T cell counts of 200-500/mm3 were randomized into thymic transplantation and control arms. All patients received HAART (zidovudine, lamivudine, and ritonavir) for 6 weeks prior to transplantation. Thymic transplantation was done without immunosuppression, using postnatal HLA-unmatched cultured allogeneic thymus tissue. Patients were immunized every 6 months with the neoantigen keyhole limpet hemocyanin (KLH) and the recall antigen tetanus toxoid (TT). T cell phenotype and function and T cell receptor rearrangement excision circles (TRECs) were assessed. Thymic allografts were biopsied at 2 months. Six HIV-infected patients completed the study. Four patients received cultured allogeneic postnatal thymic grafts, two others were controls. CD4+ T cell counts increased and T cell-proliferative responses to Candida antigen and TT normalized in all patients. Proliferative responses to KLH developed in three of four transplant recipients and one of two controls. Patients responding to KLH after secondary immunization had greater TREC increases compared with the patients who did not respond. All thymic allografts were rejected within 2 months. In summary, four of six patients developed T cell-proliferative responses to the neoantigen KLH over the first 2 years of HAART. The transplanted thymus tissue, however, was rejected. There was no clear difference in restoration of T cell function in the transplant recipients compared with the controls. Increases in TRECs after initiation of HAART may correlate with improved immune function.

Objective: To determine mortality, morbidity, and costs attributable to surgical-site infections (SSIs) in the 1990s., Design: A matched follow-up study of a cohort of patients with SSI, matched one-to-one with patients without SSI., Setting: A 415-bed community hospital., Study Population: 255 pairs of patients with and without SSI were matched on age, procedure, National Nosocomial Infection Surveillance System risk index, date of surgery, and surgeon., Outcome Measures: Mortality, excess length of hospitalization, and extra direct costs attributable to SSI; relative risk for intensive care unit (ICU) admission and for readmission to the hospital., Results: Of the 255 pairs, 20 infected patients (7.8%) and 9 uninfected patients (3.5%) died during the postoperative hospitalization (relative risk [RR], 2.2; 95% confidence interval [CI95], 1.1-4.5). Seventy-four infected patients (29%) and 46 uninfected patients (18%) required ICU admission (RR, 1.6; CI95, 1.3-2.0). The median length of hospitalization was 11 days for infected patients and 6 days for uninfected patients. The extra hospital stay attributable to SSI was 6.5 days (CI95, 5-8 days). The median direct costs of hospitalization were $7,531 for infected patients and $3,844 for uninfected patients. The excess direct costs attributable to SSI were $3,089 (CI95, $2,139-$4,163). Among the 229 pairs who survived the initial hospitalization, 94 infected patients (41%) and 17 uninfected patients (7%) required readmission to the hospital within 30 days of discharge (RR, 5.5; CI95, 4.0-7.7). When the second hospitalization was included, the total excess hospitalization and direct costs attributable to SSI were 12 days and $5,038, respectively., Conclusions: In the 1990s, patients who develop SSI have longer and costlier hospitalizations than patients who do not develop such infections. They are twice as likely to die, 60% more likely to spend time in an ICU, and more than five times more likely to be readmitted to the hospital. Programs that reduce the incidence of SSI can substantially decrease morbidity and mortality and reduce the economic burden for patients and hospitals.

Objectives: This study compared survival between patients taking dofetilide and patients taking placebo in a pooled analysis of randomized clinical trials of patients with supraventricular arrhythmias., Background: Clinical trials of antiarrhythmic drugs used to treat supraventricular arrhythmias rarely include enough patients to assess whether the drug being tested has an effect on survival. Pooling data from many trials provides useful information on safety., Methods: Data from randomized clinical trials of antiarrhythmic drug therapy of supraventricular arrhythmias were pooled to assess the effect on survival of dofetilide (n = 1346) compared with placebo (n = 677) in this patient population., Results: The unadjusted hazard ratio for risk of death (dofetilide/placebo) was 1.4 with 95% confidence interval 0.4-5.1. After adjusting for effects of arrhythmia diagnosis, age, sex, and structural heart disease, the hazard ratio was 1.1 (confidence interval 0.3-4.3)., Conclusions: The pooled survival analysis provided reassurance regarding the safety of dofetilide in patients with supraventricular arrhythmias.

Objective: To compare 5 different assays measuring collagen degradation in rheumatoid arthritis (RA)., Methods: Daily serum samples and 3 consecutive 24 h urine samples were obtained from 25 patients with RA and 20 control subjects. Levels of pyridinoline (PYD), deoxypyridinoline (DPYD), n-telopeptide (NTx), CrossLaps (XL), and carboxy-terminal peptide of type I collagen (ICTP) were determined by ELISA or radioimmunoassay. PYD, DPYD, NTx, and XL were measured in urine and expressed as a ratio of the amount of crosslink to mmoles of creatinine (Cr). ICTP was determined in serum. The day-to-day variability of urinary collagen crosslink levels and serum ICTP was assessed over 3 day hospitalization., Results: Four of the 5 markers were significantly elevated in the RA cohort compared to controls: PYD (nmol)/Cr (median 33.8 vs 19.3; p = 0.0001), NTx (nmol)/Cr (median 22.5 vs 13.8; p = 0.01), XL (microg)/Cr (median 191.4 vs 126.1; p = 0.01), and ICTP (microg/l) (median 5.8 vs 3.7; p = 0.001). In the RA group, higher levels of the markers were associated with concomitant prednisone therapy. The levels of the 4 urine markers and of ICTP in serum exhibited little day-to-day variability., Conclusion: Biochemical evidence of increased collagen degradation can be readily observed in RA using simple quantitative assays. These measures have minimal short term, day-to-day variability and hence may be useful to assess the effect of potentially disease modifying therapies.

We report our initial clinical experience with a new tined ventricular endocardial pacemaker lead, the Medtronic model 5034. This lead has a reduced electrode tip size, which provides a higher impedance. Based on early evidence of elevation of pacing lead threshold, we compared our clinical experience with the performance of this lead with that of other similar models with larger surface area (Medtronic models 4024 and 5024). Of 17 implant procedures performed at our institution with the model 5034 lead, two (11.2%) developed high thresholds, versus 0% in 121 implant procedures with models 4024 or 5024 leads (p = 0.014). We conclude that there is evidence of increased failure caused by elevation of pacing threshold in this lead. This increased failure rate needs to be confirmed in a multicenter observational study or randomized trial.

We measured left atrial function during sinus rhythm before and after ventricular tachycardia was induced in an electrophysiology laboratory, using peak transmitral A-wave velocity from pulsed-Doppler transthoracic echocardiography as a marker of left atrial mechanical function. The results of this prospective study do not support the hypothesis that a transthoracic shock of mild to moderate energy diminishes atrial mechanical function.

Nitric oxide (NO) is an important inflammatory mediator in nonhuman animal models of rheumatoid arthritis (RA). The purpose of the present study was to determine whether blood mononuclear cells from patients with active RA (as compared to control subjects) have higher levels of NO synthase type 2 (NOS2) and produce more NO in vitro. Leukocytes from 25 RA patients and 20 normal subjects were examined. Arthritis activity was assessed by tender and swollen joint counts, duration of morning stiffness, patient assessment of pain, physician and patient global assessment of disease activity, the modified Stanford Health Assessment Questionnaire, and by blood levels of acute phase reactants. Blood mononuclear cell NOS enzyme activity/antigen content and nitrite/nitrate formation in vitro were measured. Blood mononuclear cells from RA patients had increased NOS activity and increased NOS2 antigen content as compared to those from normal subjects, and responded to interferon-gamma with increased NOS expression and nitrite/nitrate production in vitro. NOS activity of freshly isolated blood mononuclear cells correlated significantly with disease activity, as assessed by render and swollen joint counts. Our results demonstrate that patients with RA have systemic activation for NOS2 expression, and that the degree of activation correlates with disease activity. Increased NOS2 expression and NO generation may be important in the pathogenesis of RA.

It is generally assumed that paroxysmal supraventricular tachycardia (PSVT) induced during invasive electrophysiological study reproduces the patient's spontaneous, clinical arrhythmia. Even in the absence of antiarrhythmic drugs, however, there may be significant differences in characteristics of the induced and spontaneous arrhythmias. We compared the heart rate of PSVT in 38 patients who had undergone electrophysiological study with induction of PSVT who also had a spontaneous episode of PSVT documented by transtelephonic ECG monitoring during a period when all antiarrhythmic drugs were withheld. The heart rate during spontaneous PSVT was faster than the heart rate of PSVT induced during electrophysiological study; the mean difference was 16 beats/min (P < 0.001). We conclude that heart rate of PSVT induced during electrophysiological study generally underestimates the heart rate of spontaneous PSVT in the antiarrhythmic drug-free state. This may be due to differences in the autonomic and hemodynamic states during spontaneous and induced arrhythmias.

Eighty normal adults were studied with MRI to investigate the relationship between regional morphology of the corpus callosum and characteristics such as age, gender, education, and cranial size. The variability coefficient was 20% in total callosal area and from 19% to 40% in regional callosal area. Increasing age and smaller cranial area were both associated with smaller total and regional callosal areas; there were no effects of gender and education. The relative effects of age and cranial size varied across regions and were most prominent for anterior subdivisions. However, age and cranial size together explained less than half the variance in regional callosal size. Further study is needed to identify additional correlates of regional callosal anatomy.

Objective: To determine the degree of loss of shoulder flexion in patients with osteoporosis, and to determine whether this was correlated with functional disability and pain as measured by the modified Health Assessment Questionnaire., Methods: Two different exercise regimens, one using traditional extension exercises of the spine (group A) and the other using both the extension exercises and exercises to stretch and strengthen scapular musculature (group B), were compared to determine their effects on range of motion, pain, and disability in 33 women with osteoporosis., Results: A significant improvement in shoulder flexion occurred in both exercise groups compared to controls; however, there were no statistically significant differences either within or between exercise groups from baseline to study end. A decrease in pain correlated with an increase in shoulder flexion in group A (r = 0.56), while an improvement in functional disability scores correlated with an increase in shoulder flexion in group B (r = 0.46)., Conclusion: Traditional spinal exercises along with exercises that target scapular mobility help to improve shoulder flexion, pain, and function in women with osteoporosis.

We conducted a retrospective cohort study of patients with Rocky Mountain spotted fever (RMSF) at a university hospital in order to assess the relationship between delay in treatment and mortality and to identify predictors of delay in initiating therapy. Patients with RMSF who received antirickettsial therapy within 5 days of the onset of symptoms were significantly less likely to die than were those who received treatment after the 5th day of illness (6.5% vs. 22.9%, respectively; P < .03). Ninety percent of patients were seen by a physician during this 5-day period, yet less than one-half of them received treatment before day 6. Three factors were independent predictors of failure by the physician to initiate therapy the first time a patient was seen: absence of a rash, presentation between 1 August and 30 April, and presentation within the first 3 days of illness. Until reliable early diagnostic tests become available, physicians may be able to decrease the mortality associated with RMSF by instituting empirical treatment of suspected cases within the first 5 days of illness.

Objectives: This study was performed to determine the incidence of symptomatic, sustained atrial fibrillation in a group of patients with paroxysmal supraventricular tachycardia. The effects of the mechanism of paroxysmal supraventricular tachycardia (atrioventricular [AV] node reentry vs. AV reentry through an accessory pathway) and heart rate during the tachycardia on the occurrence of atrial fibrillation were also assessed., Background: There is a substantial incidence of atrial fibrillation in patients with paroxysmal supraventricular tachycardia, but the precise incidence and the factors that determine it are unknown., Methods: One hundred sixty-nine patients with paroxysmal supraventricular tachycardia were followed up by regular clinic visits and transtelephonic electrocardiographic monitoring during symptomatic episodes of arrhythmia. The Kaplan-Meier product-limit method was used to estimate the proportion of patients remaining free of atrial fibrillation during the observation period. The Cox proportional hazards model was used to assess the effect of mechanism and heart rate during paroxysmal supraventricular tachycardia on the atrial fibrillation-free period., Results: Thirty-two (19%) of the 169 patients had an episode of atrial fibrillation during a mean follow-up period of 31 months. The cumulative percent of patients experiencing an episode of atrial fibrillation was 6% within 1 month, 9% within 4 months and 12% within 1 year. The mechanism of paroxysmal supraventricular tachycardia was not associated with the time to occurrence of atrial fibrillation; the hazard ratio corresponding to classification in the AV node reentry group was 0.8 (p > 0.6). The heart rate during paroxysmal supraventricular tachycardia was not associated with the time to occurrence of atrial fibrillation; the hazard ratio associated with an increase in heart rate of 50 beats/min during the tachycardia was 1.15 (p > 0.5)., Conclusions: This study suggests that atrial fibrillation will develop in approximately 12% of patients with paroxysmal supraventricular tachycardia during a 1-year follow-up period. The occurrence of atrial fibrillation is not related to the mechanism or heart rate of the paroxysmal supraventricular tachycardia.

Objective: To identify minimal sets of Mini-Mental State Examination (MMSE) items that can distinguish normal control subjects from patients with mild Alzheimer's disease (AD), patients with mild from those with moderate AD, and those with moderate from those with severe AD., Design: Two randomly selected equivalent half samples. Results of logistic regression analysis from data from the first half of the sample were confirmed by receiver operating characteristic curves on the second half., Setting: Memory disorders clinics at major medical centers in the United States affiliated with the Consortium to establish a Registry for Alzheimer's Disease (CERAD)., Participants: White, normal control subjects (n = 412) and patients with AD (n = 621) who met CERAD criteria; nonwhite subjects (n = 165) and persons with missing data (n = 27) were excluded., Main Outcome Measures: Three four-item sets of MMSE items that discriminate, respectively, (1) normal controls from patients with mild AD, (2) patients with mild from those with moderate AD, and (3) patients with moderate from those with severe AD., Results: The MMSE items discriminating normal controls from patients with mild AD were day, date, recall of apple, and recall of penny; those discriminating patients with mild from those with moderate AD were month, city, spelling world backward, and county, and those discriminating patients with moderate from those with severe AD were floor of building, repeating the word table, naming watch, and folding paper in half. Performance on the first two four-item sets was comparable with that of the full MMSE; the third set distinguished patients with moderate from those with severe AD better than chance., Conclusions: A minimum set of MMSE items can effectively discriminate normal controls from patients with mild AD and between successive levels of severity of AD. Data apply only to white patients with AD. Performance in minorities, more heterogeneous groups, or normal subjects with questionable cognitive status has not been assessed.

Patients receiving minimally symptomatic shocks from their implantable cardioverter defibrillators were studied prospectively using transtelephonic ECG loop monitoring. The time course to the first subsequent shock was evaluated. Twenty-nine consecutive patients who received a shock preceded by mild palpitations or no symptoms were given a transtelephonic ECG loop monitor and instructed to activate the monitor if a subsequent shock occurred. Kaplan-Meier analysis was used to quantitate the time to first shock during the study period. The point estimate +/- standard error of patients receiving a shock during the study period was 31% +/- 9% at 30 days, 41% +/- 9% at 60 days, and 60% +/- 9% at 120 days. The ECG was successfully transmitted in 7 of 13 patients who had shocks in the 60-day monitoring period, and demonstrated inappropriate shocks in 6 of 7. Determination of the cause of shock led to a change in subsequent management in all 7 patients. We conclude that the incidence of inappropriate shocks may be higher than estimated previously in patients with minimal symptoms prior to the shock. There are thousands of patients with implantable cardioverter defibrillators that have no storage function for treated tachycardias; transtelephonic ECG loop monitoring can determine the cause of implantable cardioverter defibrillator discharge in these patients, and the diagnosis is invaluable in their management.

Background: Paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia are recognized clinically when patients seek treatment for symptoms due to recurrent arrhythmias; atrial fibrillation also increases the risk of stroke. The frequency with which asymptomatic arrhythmias occur in patients with these arrhythmias is unknown., Methods and Results: Twenty-two patients with paroxysmal atrial fibrillation (n = 8) or paroxysmal supraventricular tachycardia (n = 14) were studied for 29 days with two different ambulatory ECG-monitoring techniques to measure the relative frequency of asymptomatic and symptomatic arrhythmias. All class I antiarrhythmic drugs, calcium channel blockers, beta-blockers, and digitalis were withheld. Sustained asymptomatic arrhythmia events (defined as lasting at least 30 seconds) were documented using continuous ambulatory ECG monitoring once weekly for a total of 5 of the 29 study days; symptomatic arrhythmia events were documented using transtelephonic ECG monitoring for all 29 days of the study. In the group of patients with paroxysmal atrial fibrillation, asymptomatic arrhythmia events occurred significantly more frequently than symptomatic arrhythmia events; the mean rates, expressed as events/100 d/patient (95% confidence interval), were 62.5 (40.4, 87.3) and 5.2 (2.7, 9.0) (P < .01); the ratio of the mean rates was 12.1 (5.8, 26.4). In contrast, in the group of patients with paroxysmal supraventricular tachycardia, asymptomatic arrhythmia events were significantly less frequent than symptomatic arrhythmia events; the mean rates were 0.0 (0.0, 5.3) and 7.4 (5.0, 10.6) (P = .02). The ratio of the mean rates was 0.0 (0.0, 0.8)., Conclusions: In a group of patients with paroxysmal atrial fibrillation, sustained asymptomatic atrial fibrillation occurs far more frequently than symptomatic atrial fibrillation. However, it is not known whether asymptomatic atrial fibrillation is a potential risk factor for stroke even when patients are not having symptomatic arrhythmias.

Background: Ambulatory outpatients (n = 150) with a history of paroxysmal supraventricular arrhythmia were studied to establish the characteristics of the first recurrence of symptomatic tachycardia (time to first recurrence, heart rate during tachycardia, and observed rhythm that was regular versus irregular) when no antiarrhythmic drug was being taken. Baseline variables were examined to assess their impact on time to first recurrence: index arrhythmia (paroxysmal atrial fibrillation [n = 37] versus paroxysmal supraventricular tachycardia [n = 113]), age (mean +/- SD, 43.3 +/- 16.1 years), female sex (n = 71), or presence of other heart or lung disease (n = 53)., Methods and Results: Transtelephonic monitoring of the ECG was used to document the rhythm during recurrences of symptomatic tachycardia. Time to first recurrence of symptomatic tachycardia and heart rate during tachycardia were measured, the observed rhythm was classified as irregular (consistent with paroxysmal atrial fibrillation) or regular (consistent with paroxysmal supraventricular tachycardia), and the hour of recurrence was recorded. Advancing age was significantly associated with a decreasing time to first recurrence (p < 0.001); the estimated increase in the hazard function was 25% with each 10 years of advancing age. After the effect of age was adjusted for, neither the classification of arrhythmia (p > 0.2), presence of other heart or lung disease (p > 0.8), nor sex (p > 0.9) was significantly associated with time to first recurrence. Among patients with paroxysmal supraventricular tachycardia, 6.5% had atrial fibrillation recorded at the next symptomatic arrhythmia; among patients with paroxysmal atrial fibrillation, 11.8% had a regular tachycardia recorded at the next symptomatic arrhythmia. There was a circadian pattern to the hour of occurrence of paroxysmal supraventricular tachycardia but not paroxysmal atrial fibrillation., Conclusions: Age is more important than other clinical variables, including the ECG classification of a paroxysmal supraventricular arrhythmia in predicting the occurrence of symptomatic arrhythmias. Arrhythmias documented by ECG during symptoms are often different from the arrhythmia documented at the time of referral, which may confound interpretation of antiarrhythmic drug effects.

To determine whether structural brain abnormalities in patients with depression are related to cortisol state, we examined the relationship between the dexamethasone suppression test (DST) and brain magnetic resonance imaging (MRI) in 40 inpatients with severe depression referred for electroconvulsive therapy (ECT). Prior to ECT, 27 (68%) of the patients exhibited nonsuppression on the DST. Frontal lobe volume was negatively correlated with peak post-dexamethasone cortisone (r = -0.37) and was 13% smaller in DST nonsuppressors than suppressors; these findings were no longer significant after adjustments for age, gender, and cranial size. Lateral and third ventricular volumes were also correlated with peak postdexamethasone cortisol (r = 0.34 and 0.33, respectively), but not after adjustments for age, gender, and cranial size. Subcortical hyperintensity was associated with peak postdexamethasone cortisol and was more common in DST nonsuppressors than suppressors. Again these findings were no longer significant after adjustments for age. Finally, longitudinal DST and brain MRI studies in 11 of these patients revealed no changes in regional brain volumes nor in postdexamethasone cortisol up to six months after ECT. However, within individual patients, postdexamethasone cortisol was positively (and significantly) correlated with frontal lobe volume.

Magnetic resonance imaging was used to examine cerebral anatomy in 48 inpatients with severe depression who were referred for electroconvulsive therapy and in 76 normal control subjects. The magnetic resonance imaging measures included determinations of regional cerebral volumes and ratings of the frequency and severity of cortical atrophy, lateral ventricular enlargement, and subcortical hyperintensity. The mean total frontal lobe volume was found to be 7% smaller in the inpatients with severe depression (235.88 mL) than in the normal control subjects (254.32 mL)--a difference that was statistically significant even after adjusting for the effects of age, sex, education, and intracranial size. No group differences were observed in the volumes of the cerebral hemispheres, the temporal lobes, or the amygdala-hippocampal complex, nor in the frequency of cortical atrophy. Neither did the groups differ with respect to the total volumes of the lateral and third ventricles, nor in the frequency of lateral ventricular enlargement. Patients with depression had a significantly higher frequency of subcortical hyperintensity in the periventricular white matter, with an odds ratio of 5.32.

1. This retrospective study examined the magnitude of the problem of work related health hazards affecting professional and non-professional employees of a state university health science center and hospital. 2. From the 1,513 injury episodes that occurred among the 9,668 employees during the 32 month study period, it was determined that the highest risk categories for both department and job were nursing, housekeeping, food service, and laboratory technicians. 3. Injury rate for females (11.2 per 100 person years) was more than twice that of males (5.1). Injury rates declined from 11.6 per 100 person years at ages 25 to 39 to 3.8 at ages over 60. Puncture wounds (32.7%), mostly by needlesticks, were the most frequently reported injury type, followed by strains and sprains (17.2%), lacerations (12.5%), and contusions (12.1%).

Symptomatic paroxysmal supraventricular tachycardia is a troubling arrhythmia for many patients. To test the efficacy of oral diltiazem to reduce symptomatic recurrences of paroxysmal supraventricular tachycardia, we enrolled 17 patients in a double-blind, placebo-controlled crossover study. Sixteen of 17 patients completed a dose-ranging phase and were entered into the randomized phase. Although the time to first recurrence of tachycardia was slightly longer when patients took diltiazem, the difference was not significant (p = 0.15). The hazard ratio of the time to first recurrence on placebo compared with oral diltiazem was 2.7 (95% confidence interval, 0.8 to 9.1). Of the patients who had a recurrence of tachycardia in both treatment periods, the median reduction in heart rate in patients receiving diltiazem was 20 beats/min. (p less than 0.01; 95% confidence interval, 6 to 42).

Forty-nine healthy male volunteers received the test article for bidisomide (SC-40230) in a double-blind, placebo-controlled, dose-ranging study. Intravenous doses ranged from 0.03 to 2.5 mg/kg. There was a close relationship between the dose and the peak plasma concentration. The PR, QRS, QT, RR, and QTc intervals each demonstrated a statistically significant response to the dose administered. The PR and QRS intervals lengthened and the other intervals shortened (although to a lesser degree). The compound was well tolerated, with mild symptoms only at higher doses. Bioavailability was studied in 12 male volunteers, with each receiving 2.0 mg/kg of bidisomide, both orally and intravenously, in an open-label crossover trial. After a 10-minute zero-order intravenous infusion, bidisomide plasma levels could best be described in terms of a three-compartment pharmacokinetic model with the mean half-life values of alpha, beta, and gamma phases of 0.12, 1.77, and 12.3 hours, respectively. The mean absolute oral bioavailability was 43%.

Seventy-six healthy adults underwent magnetic resonance imaging (1.5 T) to investigate the effects of age on regional cerebral volumes and on the frequency and severity of cortical atrophy, lateral ventricular enlargement, and subcortical hyperintensity. Increasing age was associated with (1) decreasing volumes of the cerebral hemispheres (0.23% per year), the frontal lobes (0.55% per year), the temporal lobes (0.28% per year), and the amygdala-hippocampal complex (0.30% per year); (2) increasing volumes of the third ventricle (2.8% per year) and the lateral ventricles (3.2% per year); and (3) increasing odds of cortical atrophy (8.9% per year), lateral ventricular enlargement (7.7% per year), and subcortical hyperintensity in the deep white matter (6.3% per year) and the pons (8.1% per year). Many elderly subjects did not exhibit cortical atrophy or lateral ventricular enlargement, however, indicating that such changes are not inevitable consequences of advancing age. These data should provide a useful clinical context within which to interpret changes in regional brain size associated with "abnormal" aging.

To determine prospectively whether electroconvulsive therapy (ECT) produces structural brain changes, 35 inpatients with depression underwent magnetic resonance imaging before and twice after (at 2 to 3 days and at 6 months) completion of a course of brief-pulse, bilateral ECT. The magnetic resonance images were analyzed blindly for evidence of changes in brain structure using two approaches: measurement of regional brain volumes and a pairwise global comparison. Structural brain abnormalities were present in many patients before ECT. The course of ECT produced no acute or delayed (6-month) change in brain structure as measured by alterations of the total volumes of the lateral ventricles, the third ventricle, the frontal lobes, the temporal lobes, or the amygdala-hippocampal complex. In five subjects, the pairwise global comparisons revealed an apparent increase in subcortical hyperintensity, most likely secondary to progression of ongoing cerebrovascular disease during follow-up. Our results confirm and extend previous imaging studies that also found no relationship between ECT and brain damage.