William M. Rand

Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction

OBJECTIVES We sought to evaluate the relationship between the level of kidney function, level of hematocrit and their interaction on all-cause mortality in patients with left ventricular (LV) dysfunction. BACKGROUND Anemia and reduced kidney function occur frequently in patients with heart failure. The level of hematocrit and its relationship with renal function have not been evaluated as risk factors for mortality in patients with LV dysfunction. METHODS We retrospectively examined the Studies Of LV Dysfunction (SOLVD) database. Glomerular filtration rate (GFR) was predicted using a recently validated formula. Kaplan-Meier survival analyses were used to compare survival times between groups stratified by level of kidney function (predicted GFR) and hematocrit. Cox proportional-hazards regression was used to explore the relationship of survival time to level of kidney function, hematocrit and their interaction. RESULTS Lower GFR and hematocrit were associated with a higher prevalence of traditional cardiovascular risk factors. In univariate analysis, reduced kidney function and lower hematocrit, in men and in women, were risk factors for all-cause mortality (p < 0.001 for both). After adjustment for other factors significant in univariate analysis, a 10 ml/min/1.73 m(2) lower GFR and a 1% lower hematocrit were associated with a 1.064 (95% CI: 1.033, 1.096) and 1.027 (95% CI: 1.015, 1.038) higher risk for mortality, respectively. At lower GFR and lower hematocrit, the risk was higher (p = 0.022 for the interaction) than that predicted by both factors independently. CONCLUSIONS Decreased kidney function and anemia are risk factors for all-cause mortality in patients with LV dysfunction, especially when both are present. These relationships need to be confirmed in additional studies.

Nonsurgical factors that influence the outcome of bariatric surgery: a review.

Objective Severe obesity (ie, at least 100% overweight or body mass index >or=to40 kg/m2) is associated with significant morbidity and increased mortality. It is apparently becoming more common in this country. Conventional weight-loss treatments are usually ineffective for severe obesity and bariatric surgery is recommended as a treatment option. However, longitudinal data on the long-term outcome of bariatric surgery are sparse. Available data indicate that the outcome of bariatric surgery, although usually favorable in the short term, is variable and weight regain sometimes occurs at 2 years after surgery. The objective of this study is to present a review of the outcome of bariatric surgery in three areas: weight loss and improvement in health status, changes in eating behavior, and psychosocial adjustment. The study will also review how eating behavior, energy metabolism, and psychosocial functioning may affect the outcome of bariatric surgery. Suggestions for additional research in these areas are made. Method Literature review. Results On average, most patients lose 60% of excess weight after gastric bypass and 40% after vertical banded gastroplasty. In about 30% of patients, weight regain occurs at 18 months to 2 years after surgery. Binge eating behavior, which is common among the morbidly obese, may recur after surgery and is associated with weight regain. Energy metabolism may affect the outcome of bariatric surgery, but it has not been systematically studied in this population. Presurgery psychosocial functioning does not seem to affect the outcome of surgery, and psychosocial outcome is generally encouraging over the short term, but there are reports of poor adjustment after weight loss, including alcohol abuse and suicide. Conclusions Factors leading to poor outcome of bariatric surgery, such as binge eating and lowered energy metabolism, should be studied to improve patient selection and outcome. Long-term outcome data on psychosocial functioning are lacking. Longitudinal studies to examine the long-term outcome of bariatric surgery and the prognostic indicators are needed.

Antiplatelet Agents and Survival: A Cohort Analysis From the Studies of Left Ventricular Dysfunction (SOLVD) Trial

OBJECTIVES This study sought to evaluate the relation between antiplatelet agent (APA) use and survival and morbidity from cardiac disease in patients with left ventricular (LV) systolic dysfunction. BACKGROUND APAs play an important role in the prevention and treatment of coronary disease. Their effects in patients with LV systolic dysfunction are unknown. METHODS We reviewed data on APA use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between their use and all-cause mortality as well as the combined end point of death or hospital admission for heart failure (HF). We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between APA use and selected patient variables in relation to outcome. RESULTS APA use (46.3% of patients) was associated with significantly reduced mortality from all causes (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.73 to 0.92, p = 0.0005) and reduced risk of death or hospital admission for HF (adjusted HR 0.81, 95% CI 0.74 to 0.89, p < 0.0001) but was not influenced by trial assignment, gender, LV ejection fraction, New York Heart Association class or etiology. A strong interaction was observed among APA use, randomization group and all-cause mortality. The association between APA use and survival was not observed in the enalapril group, nor was an enalapril benefit on survival detectable in patients receiving APAs at baseline. However, randomization to enalapril therapy significantly reduced the combined end point of death or hospital admission for HF in APA users. CONCLUSIONS In patients with LV systolic dysfunction, use of APAs is associated with improved survival and reduced morbidity. This association is retained after adjustment for baseline characteristics. APA use is associated with retained but reduced benefit from enalapril.

Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease

OBJECTIVES We studied whether assessment of endothelium-dependent vasomotion (EDV) with brachial artery ultrasound (BAUS) imaging predicts the presence or absence of coronary artery disease (CAD) as defined by exercise myocardial perfusion imaging (ExMPI). BACKGROUND Abnormalities in EDV can be detected in arteries before the development of overt atherosclerosis, and its presence may predict poor long-term prognosis. Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral EDV. METHODS Clinically-indicated ExMPI along with BAUS were performed in 94 subjects (43 women, 51 men). Coronary artery disease was defined by myocardial ischemia or infarction on single photon emission computed tomography images. Flow-mediated dilation (FMD) after upper arm occlusion was defined as the percent change in arterial diameter during reactive hyperemia relative to the baseline. RESULTS Subjects with CAD by ExMPI (n = 23) had a lower FMD (6.3 +/- 0.7%) than those without CAD by ExMPI (n = 71) (10.5 +/- 0.6%; p = 0.0004). Flow-mediated dilation was highly predictive for CAD with an odds ratio of 1.32 for each percent decrease in FMD (p = 0.001). Based on a receiver-operator analysis, an FMD of 10% was used as a cut-point for further analysis. Twenty-one of 23 subjects who were positive for ExMPI had an FMD < 10% (sensitivity 91%), whereas only two of 40 subjects with an FMD > or =10% were ExMPI-positive (negative predictive value: 95%). There was a correlation between the number of cardiac risk factors and FMD. Individuals with an FMD < 10% exercised for a shorter duration than those with an FMD > or =10% (456 +/- 24 vs. 544 +/- 31 s, respectively; p = 0.02). CONCLUSIONS Assessment of EDV with BAUS has a high sensitivity and an excellent negative predictive value for CAD and, thus, has the potential for use as a screening tool to exclude CAD in low-risk subjects. Further standardization of BAUS is required, however, before specific cut-points for excluding CAD can be established.

Quantitative assay for mutation in diploid human lymphoblasts using microtiter plates

We describe a microtiter plating technique which eliminates the need for soft agar and fibroblast feeder layers to determine the colony-forming ability of diploid human lymphoblast lines. The calculation of cloning efficiency is based on the Poisson distribution, and we present a statistical method for calculating confidence intervals. We have applied this technique to the comcomitant examination of induced mutation at the putative loci for hypoxanthine guanine phosphoribosyl transferase, thymidine, kinase, and Na+/K+ adenosine triphosphatase.

Cauda equina syndrome and lumbar disc herniation.

In a retrospective chart review of the cases of thirty-one patients with cauda equina syndrome secondary to a central disc lesion, we identified two modes of presentation. The first was an acute mode (ten patients) in which there were abrupt, more severe symptoms and signs and a slightly poorer prognosis after decompression, especially for the return of bladder function. The second mode of presentation (twenty-one patients) was a slower onset, characterized by prior symptoms for varying time-intervals before the more gradual onset of the cauda equina syndrome. All patients had urinary retention preoperatively. Bladder function was the most seriously affected function preoperatively and remained so postoperatively. The prognosis for return of motor function was good, since twenty-seven of the thirty patients who were operated on regained normal motor function. Preoperatively all patients had sciatica, which was bilateral in fourteen and unilateral in seventeen. The average time to surgical decompression after the patient was seen ranged from 1.1 days for the more acute lesions to 3.3 days for the second group. There was no correlation of these times with return of function. Therefore, even though early surgery is recommended, decompression does not have to be performed in less than six hours if recovery is to occur, as has been suggested in the past.

Warfarin Anticoagulation and Survival: A Cohort Analysis From the Studies of Left Ventricular Dysfunction

OBJECTIVES We sought to evaluate the relation between warfarin anticoagulation and survival and morbidity from cardiac disease in patients with left ventricular (LV) dysfunction. BACKGROUND Warfarin anticoagulation plays a major role in the management of patients who have had a large myocardial infarction and in those with atrial fibrillation. However, its use in patients with LV systolic dysfunction has been controversial. METHODS We reviewed data on warfarin use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between warfarin use and all-cause mortality, as well as the combined end point of death or hospital admission for heart failure. We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between warfarin use and selected patient variables in relation to outcome. RESULTS On multivariate analysis, use of warfarin was associated with a significant reduction in all-cause mortality (adjusted hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.65 to 0.89, p = 0.0006) and in the risk of death or hospital admission for heart failure (HR 0.82, 95% CI 0.72 to 0.93, p = 0.0002). Risk reduction was observed when each trial or randomization arm was analyzed separately, as well as in both genders. It was not significantly influenced by the presence of atrial fibrillation, age, ejection fraction, New York Heart Association functional class or etiology. CONCLUSIONS In patients with LV systolic dysfunction, warfarin use is associated with improved survival and reduced morbidity. This association is primarily due to a reduction in cardiac events and does not appear to be limited to any particular subgroup.

Binge eating disorder in extreme obesity.

OBJECTIVE: To determine whether extremely obese binge eating disorder (BED) subjects (BED defined by the Eating Disorder Examination) differ from their extremely obese non-BED counterparts in terms of their eating disturbances, psychiatric morbidity and health status.DESIGN: Prospective clinical comparison of BED and non-BED subjects undergoing gastric bypass surgery (GBP).SUBJECTS: Thirty seven extremely obese (defined as BMI ≥40 kg/m2) subjects (31 women, six men), aged 22–58 y.MEASUREMENTS: Eating Disorder Examination 12th Edition (EDE), Three Factor Eating Questionnaire (TFEQ), Structured Clinical Interview for the Diagnostic and Statistical Manual-IV (SCID-IV), Short-Form Health Status Survey (SF-36), and 24 h Feeding Paradigm.RESULTS: Twenty-five percent of subjects were classified as BED (11% met full and 14% partial BED criteria) and 75% of subjects were classified as non-BED. BED (full and partial) subjects had higher eating disturbance in terms of eating concern and shape concern (as found by the EDE), higher disinhibition (as found by the TFEQ), and they consumed more liquid meal during the 24 h feeding paradigm. No difference was found in psychiatric morbidity between BED and non-BED in terms of DSM-IV Axis I diagnosis. The health status scores of both BED and non-BED subjects were significantly lower than US norms on all subscales of the SF-36, particularly the BED group.CONCLUSION: Our findings support the validity of the category of BED within a population of extremely obese individuals before undergoing GBP. BED subjects differed from their non-BED counterparts in that they had a greater disturbance in eating attitudes and behavior, a poorer physical and mental health status, and a suggestion of impaired hunger/satiety control. However, in this population of extremely obese subjects, the stability of BED warrants further study.

EBV and Systemic Lupus Erythematosus: A New Perspective

We have proposed that EBV uses mature B cell biology to access memory B cells as a site of persistent infection. A central feature of this model is that EBV adapts its gene expression profile to the state of the B cell it resides in and that the level of infection is stable over time. This led us to question whether changes in the behavior or regulation of mature B cells would alter the state of EBV persistence. To investigate this, we studied the impact of systemic lupus erythematosus (SLE), a disease characterized by immune dysfunction, on EBV infection. We show that patients with SLE have abnormally high frequencies of EBV-infected cells in their blood, and this is associated with the occurrence of SLE disease flares. Although patients with SLE have frequencies of infected cells comparable to those seen in immunosuppressed patients, in SLE the effect was independent of immunosuppressive therapy. Aberrant expression of viral lytic (BZLF1) and latency (latency membrane proteins 1 and 2a) genes was also detected in the blood of SLE patients. We conclude that the abnormal regulation of EBV infection in SLE patients reflects the sensitivity of the virus to perturbation of the immune system.

Neuropeptide Y Has a Central Inhibitory Action on the Hypothalamic-Pituitary-Thyroid Axis.

Recent evidence suggests that neuropeptide Y (NPY), originating in neurons in the hypothalamic arcuate nucleus, is an important mediator of the effects of leptin on the central nervous system. As these NPY neurons innervate hypophysiotropic neurons in the hypothalamic paraventricular nucleus (PVN) that produce the tripeptide, TRH, we raised the possibility that NPY may be responsible for resetting of the hypothalamic-pituitary-thyroid (HPT) axis during fasting. To test this hypothesis, the effects of intracerebroventricularly administered NPY on circulating thyroid hormone levels and proTRH messenger RNA in the PVN were studied by RIA and in situ hybridization histochemistry, respectively. NPY administration suppressed circulating levels of thyroid hormone (T(3) and T(4)) and resulted in an inappropriately normal or low TSH. These alterations were associated with a significant suppression of proTRH messenger RNA in the PVN, indicating that NPY infusion had resulted in a state of central hypothyroidism. Similar observations were made in NPY-infused animals pair fed to the vehicle-treated controls. These data are reminiscent of the effect of fasting on the thyroid axis and indicate that NPY may play a major role in the inhibition of HPT axis during fasting.