Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

The effect of apomorphine on regional cerebral blood flow in schizophrenia

A double-blind, placebo-controlled crossover study of the effects of apomorphine on regional cerebral blood flow (rCBF) during a prefrontal cortex activation task was undertaken to explore the role of dopamine on cortical function. The subjects were eight drug-free, chronically psychotic patients; six patients had schizophrenia. In each, apomorphine increased the relative prefrontal flow. The results suggest that enhanced prefrontal dopamine activity may reverse deficits in prefrontal cortex metabolism in schizophrenia.     

Osteoporosis and Coronary Atherosclerosis in Asymptomatic Postmenopausal Women

Estrogen deficiency is a risk factor for osteoporosis and coronary artery disease. Osteoporosis can be evaluated by measuring bone mineral density (BMD). Coronary atherosclerotic burden can be evaluated by measuring coronary calcium using electron beam computed tomography (EBT) of the heart. We compared coronary calcium scores in 45 asymptomatic postmenopausal women with normal and low BMD. BMD of the lumbar spine and proximal femur was measured by dual X-ray absorptiometry (DXA), and coronary calcium was measured quantitatively by EBT. Women were divided into control, osteopenia, and osteoporosis groups based on the T score of the lumbar spine. Women were similar in age, years since menopause, height, weight, and body mass index (BMI). BMD ± SD (g/cm²) of L1–L4 was 0.96 ± 0.11, 0.83 ± 0.03, and 0.73 ± 0.05, in control, osteopenia, and osteoporosis group, respectively. The total coronary calcium score ± SD (relative units) was 41.9 ± 83.1, 115.1 ± 181.9, and 221.7 ± 355.4 for control, osteopenia, and osteoporosis group, respectively; the score was significantly higher in the osteoporosis than in the control group. This study provides initial data suggesting that women with osteoporosis may have a higher risk of developing coronary atherosclerosis.     

The Influence of Routine Completion Arteriography on Outcome following Carotid Endarterectomy

n = 69) normal; Group B (n= 29), abnormal, severe defects; Group C (n= 56), abnormal, mild–moderate defect. RCA detected 32 defects in Group B: 10 internal carotid (ICA), seven endpoint flaps, two kinks, one dissection; 16 external carotid (ECA), 10 severe endpoint defects and six total occlusion; six common carotid (CCA), five irregular proximal shelfs, one web. Thirty of 32 defects were successfully repaired as confirmed by normal repeat RCA studies; one ECA defect was not repaired and the ICA dissection was irreparable. In Group C, 67 mild–moderate defects were identified, but not corrected. These included <30% stenosis in the ICA (12), ECA (18), CCA (24), and vein patch corrugation or irregularity (13). For the entire series the postoperative ICA occlusion rate was 2% (3/154), stroke rate 2.6% (4/154), and a subsequent >50% restenosis rate of 7% (11/154). The yield from routine carotid completion arteriograms was significant, with 19% of studies identifying a severe defect that required repair. Although the difference in stroke rates and restenosis between the different groups did not reach statistical significance, patients with normal intraoperative arteriograms initially or after correction of a significant RCA defect had no early carotid occlusion (p= 0.05, Fisher's exact test) compared to patients with residual RCA defects. All early carotid occlusions occurred in patients with unrepaired defects. We conclude that RCA is an important method of quality control after CEA and exerts a subtle, but real, reduction in postoperative complications.     

Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis

Administration of an elemental diet to rats given methotrexate (MTX), 20 mg/kg intraperitoneally (ip), results in 100% mortality from severe enterocolitis. Previous studies indicate that glutamine (GLN), which is not present in elemental diets, is the preferred oxidative substrate for the gut and may facilitate intestinal recovery after injury. This study investigated the effects of a glutamine-supplemented elemental diet (GLN-ED) on nutritional status, intestinal morphometry, bacterial translocation and survival in this lethal model of intestinal injury. Three experiments were performed. In the first experiment, rats received an intragastric elemental diet supplemented with either 2% GLN or an equivalent amount of glycine (Control). After 4 days animals received either MTX, 20 mg/kg ip, or saline ip and were killed 3 days later. The GLN-ED resulted in significantly decreased weight loss, improved nitrogen retention, and increased mucosal weight, protein, and DNA content of the jejunum and colon. In the second experiment rats were assigned to diet as in the first experiment, but all animals received MTX. Control diet animals died within 120 hrs of MTX administration. The GLN-ED group had significantly longer survival time and decreased mortality. In the third experiment animals were assigned to diet and MTX as in the first experiment. Ninety-six hrs later aortic blood cultures revealed enteric bacteremia in animals administered MTX. GLN-ED resulted in a significant reduction in the incidence of bacteremia. These experiments showed that a GLN-ED significantly improved nutritional status, decreased intestinal injury, decreased bacterial translocation, and resulted in improved survival in a lethal model of enterocolitis.     

Clustering of autoimmune disease in parents of siblings from the Type 1 diabetes Warren repository.

AIMS: Autoimmune disorders co-exist in the same individuals and in families, implying a shared aetiology. The aim of this study was to compare the prevalence of the common autoimmune diseases in the parents of siblings from the Type 1 diabetes Warren repository with the general population. METHODS: Between 1989 and 1996, 505 British families with at least two siblings affected by Type 1 diabetes were recruited. Clinical information was collected regarding the presence of autoimmune disease in the parents and the prevalence of disease in the parents was compared with that expected in the general population. RESULTS: The prevalence of autoimmune disease in the parents was significantly higher in the repository compared with that expected in the general population [P-value = 1.98 x 10(-5) (female), P-value = 1.1 x 10(-8) (male)]. Type 1 diabetes was recorded in 63/1010 (6.2%) parents with a marked paternal preponderance (9.5 vs. 3%P = 0.002). Other autoimmune diseases affected 27% of parents with diabetes and 13.2% of parents without diabetes (P < 0.01). CONCLUSION: These data confirm the importance of family history as a significant risk factor for the development of Type 1 diabetes and support the hypothesis that the common autoimmune diseases share at least some aetiological mechanisms.     

Using jugular bulb oxyhemoglobin saturation to guide onset of deep hypothermic circulatory arrest does not affect post-operative neuropsychological function.

OBJECTIVES: Deep hypothermic circulatory arrest (DHCA) is commonly used during thoracic aortic surgery, and is initiated only after a sufficient degree of cerebral hypothermia is induced. The criteria for initiating DHCA vary among institutions: most centers use temperature criteria, some use electroencephalography, and a minority use jugular bulb oxyhemoglobin saturation SjO(2) criteria. The purpose of this study was to determine whether the use of SjO(2) monitoring to guide the onset of DHCA was associated with better post-operative neuropsychological outcome. METHODS: Sixty-one thoracic aortic surgical patients underwent both pre- and post-operative neuropsychological testing. Patients were divided into three groups: (1) those with SjO(2)> or =95% at DHCA onset; (2) those with SjO(2)<95% at DHCA onset; and (3) those without SjO(2) monitoring. RESULTS: There were no statistically significant differences in the incidence of post-operative decline in neuropsychological function among the three groups of patients. Patients in whom SjO(2) data were used to guide onset of DHCA had lower esophageal and bladder temperatures at that time compared with patients without SjO(2) monitoring. CONCLUSIONS: Monitoring of SjO(2) had no apparent effect upon post-operative neuropsychological outcome, and there were no trends in our small patient cohort suggesting differences that our study was not adequately powered to detect. Use of SjO(2) monitoring was associated with more profound hypothermia prior to DHCA due to more prolonged cooling in attempts to bring the SjO(2) above the 95% threshold. Using our institutional cooling protocol, SjO(2) monitoring does not appear to increase neuroprotection in patients undergoing DHCA for thoracic aortic repairs.     

Self-Warming Lidocaine/Tetracaine Patch Effectively and Safely Induces Local Anesthesia during Minor Dermatologic Procedures

BACKGROUND Dermatologic procedures often cause some degree of pain. A self-warming patch containing lidocaine and tetracaine (L/T) was developed to provide topical local anesthesia prior to painful procedures.
OBJECTIVES To evaluate the safety and efficacy of a self-warming L/T patch to provide anesthesia in adult patients undergoing minor dermatologic procedures.
METHODS An active or placebo study drug was placed on adults 30 minutes prior to minor dermatologic surgical procedures in a prospectively randomized, double-blinded manner. Subcutaneous lidocaine injection was available during the procedure as a rescue medication if requested by the subject. Immediately following the procedure, the subjects, the investigator, and an independent observer rated pain intensity and adverse events were recorded.
RESULTS Patient-reported pain intensity was significantly lower in the L/T patch group (   p < .001  ). Investigators and an independent observer rated the pain in the L/T patch group to be less than in the placebo patch group (   p = .004  and   p < .001  , respectively). Forty-nine percent of patients in the placebo group required rescue subcutaneous lidocaine compared with 22% in the L/T patch study group (   p = .008  ). One patient in the L/T patch group reported a transient moderate burning sensation.
CONCLUSION The self-warming L/T patch was effective in providing clinically useful local anesthesia for minor dermatologic procedures in adult patients.
ZARS, INC., PROVIDED SUPPORT VIA A SPONSORED RESEARCH GRANT TO THE UNIVERSITY OF MIAMI.