Continuing studies on the cyanobacterium Lyngbya sp.: isolation and structure determination of 15-norlyngbyapeptin A and lyngbyabellin D

Re-collections of the cyanobacterium Lyngbya sp. have yielded two more members of the lyngbyapeptin and lyngbyabellin families. The gross structures of 15-norlyngbyapeptin A (1) and lyngbyabellin D (3) were deduced through standard 2D NMR techniques, with the absolute configuration of both elucidated through degradation and comparison with commercially available and synthetic standards. Degradation to the alpha-amino acid and NOE correlations determined the absolute and relative configuration of the 4-amino-3-hydroxy-5-methylhexanoic acid unit in 3. Lyngbyabellin D (3) displayed an IC(50) value of 0.1 microM against the KB cell line.     

Detection of coronary artery stenoses with multislice helical CT angiography

OBJECTIVES: The authors compared multislice CT angiography and selective angiography for the assessment of coronary artery disease. METHODS: In 28 patients, the presence and degree of coronary artery stenoses were determined in coronary segments prepared with beta-blocker for good image quality with multislice CT. RESULTS: In 187 coronary artery segments, sensitivity, specificity, and negative predictive value for the detection of stenoses >50% with multislice CT angiography were 81%, 90%, and 97%, respectively. The agreement for determining the degree of stenoses with multislice CT angiography and selective coronary angiography was only moderate (kappa = 0.58). CONCLUSIONS: Because of the limited spatial resolution, it is not possible with multislice CT angiography to determine the degree the coronary artery stenoses precisely. However, the high negative predictive value indicates that multislice CT may be a suitable tool to reliably rule out coronary artery disease.     

A new expandable venous cannula for minimal access heart surgery

BACKGROUND: During percutaneous cannulation, the diameter of the venous cannula is determined by the size of the access site. To limit this restriction, the Smart cannula (Cardiosmart Ltd., Fribourg, Switzerland) has been developed. Because its design allows self-expansion within the recipient vein, diameter restriction is limited to the access site. METHODS: In 6 calves (78 +/- 4.3 kg), the jugular vein and the carotid artery were cannulated through a cervicotomy. The Smart cannula was tested against three percutaneous cannulas with a diameter of 27, 25, and 21F, respectively. Stenotic percutaneous access to the vein was simulated by 1-cm wide tape encircling the vein that could be adjusted to a diameter of 27, 25, and 21F, respectively. The maximal flow rate, reached with stable reservoir level and a negative pressure of 44 mm Hg, was determined three times for each access size with the Smart cannula (one size fits all) and the corresponding percutaneous cannula successively. RESULTS: For an access size of 27F, the flow of the Smart cannula was 5.7 +/- 0.4 L/min and that of the percutaneous cannula was 4.3 +/- 0.2 L/min (p < 0.0001); for 25F, flow rates were 5.6 +/- 0.5 and 3.9 +/- 0.2 L/min, respectively (p < 0.0001); and for 21F, the flow rates were 4.3 +/- 0.4 and 2.7 +/- 0.3 L/min, respectively (p < 0.0001). The percentage increase of flow for the 27, 25, and 21F sizes were 34% +/- 9%, 42% +/- 16%, and 53% +/- 18%, respectively (one-way analysis of variance, p = 0.014). CONCLUSIONS: For the present set-up, the Smart cannula outperforms commercially available percutaneous cannulas. The smaller the size of the insertion site, we observed a higher gain of flow with the Smart cannula.     

Atrial fibrillation and minimally invasive coronary artery bypass grafting: risk factor analysis

Atrial fibrillation (AF) is a frequent arrhythmia after conventional coronary artery bypass grafting. With the advent of minimally invasive technique for left internal mammary artery-left anterior descending coronary artery (LIMA-LAD) grafting, we analyzed the incidence and the risk factors of postoperative AF in this patient population. This prospective study involves all patients undergoing isolated LIMA-LAD grafting with minimally invasive technique between January 1994 and June 2000. Twenty-four possible risk factors for postoperative AF were entered into univariate and multivariate logistic regression analyses. Postoperative AF occurred in 21 of the 90 patients (23.3%) analyzed. Double- or triple-vessel disease was present in 12/90 patients (13.3%). On univariate analysis, right coronary artery disease (p <0.01), age (p = 0.01), and diabetes (p = 0.04) were found to be risk factors for AF. On multivariate analysis, right coronary artery disease was identified as the sole significant risk factor (p = 0.02). In this patient population, the incidence of AF after minimally invasive coronary artery bypass is in the range of that reported for conventional coronary artery bypass grafting. Right coronary artery disease was found to be an independent predictor, and this may be related to the fact that in this patient population the diseased right coronary artery was not revascularized at the time of the surgical procedure. For the same reason, this risk factor may find a broader application to noncardiac thoracic surgery.     

Addition of AT1 blocker fails to overcome resistance to ACE inhibition in adriamycin nephrosis

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors provide renoprotection, but there is considerable interindividual variability in therapeutic efficacy, with residual proteinuria and progressive renal function loss in many individuals. This requires additional strategies to optimize therapy response, particularly for individuals with a poor response to ACE inhibition. We studied whether co-treatment with an angiotensin II subtype 1 (AT1) receptor antagonist (AII-A) improves the individual antiproteinuric response of maximal ACE inhibition in established adriamycin nephrosis. METHODS: Rats were instituted on lisinopril (75 mg/L) six weeks after disease induction. After two weeks rats were re-stratified for residual proteinuria to continue this regimen, to a higher dose of lisinopril (150 mg/L) or to co-treatment with the AII-A L 158,809 for another four weeks. Groups on monotherapy AII-A and vehicle served as controls (all groups N=15). RESULTS: Lisinopril lowered proteinuria by 63% from 741 to 246 g/day (range of percentage change -90 to +2%). Neither increasing the dose of the ACE inhibitor nor addition of AII-A to ACE inhibition improved the antiproteinuric efficacy on a group or individual level: non-responders remained non-responders. All drug categories reduced hard end-points of focal glomerulosclerosis to a similar degree. CONCLUSIONS: ACE inhibition has variable renal protective efficacy in the adriamycin model. Neither increasing the dose of the ACE inhibitor beyond the optimal level nor co-treatment with AII-A overcome the individual therapy resistance. Thus, in established adriamycin nephrosis, blockade of the renin-angiotensin system at two different levels offers no additional benefit over ACE inhibition alone, either on the group or individual level.     

Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial

Context  Coronary artery bypass graft (CABG) surgery is associated with a decline in cognitive function, which has largely been attributed to the use of cardiopulmonary bypass (on-pump procedures). Cardiac stabilizers facilitate CABG surgery without use of cardiopulmonary bypass (off-pump procedures) and should reduce the cognitive decline associated with on-pump procedures. Objective  To compare the effect of CABG surgery with (on-pump) and without (off-pump) cardiopulmonary bypass on cognitive outcome. Design and Setting  Randomized controlled trial conducted in the Netherlands of CABG surgery patients enrolled from March 1998 through August 2000, with 3- and 12-month follow-up. Participants and Intervention  Patients scheduled for their first CABG surgery (mean age, 61 years; n = 281) were randomly assigned to off-pump surgery (n = 142) or on-pump surgery (n = 139). Main Outcome Measures  Cognitive outcome at 3 and 12 months, which was determined by psychologists (blinded for randomization) who administered 10 neuropsychological tests before and after surgery. Quality of life, stroke rate, and all-cause mortality at 3 and 12 months were secondary outcome measures. Results  Cognitive outcome could be determined at 3 months in 248 patients. Cognitive decline occurred in 21% in the off-pump group and 29% in the on-pump group (relative risk [RR], 0.65; 95% confidence interval [CI], 0.36-1.16; P = .15). The overall standardized change score (ie, improvement of cognitive performance) was 0.19 in the off-pump vs 0.13 in the on-pump group (P = .03). At 12 months, cognitive decline occurred in 30.8% in the off-pump group and 33.6% in the on-pump group (RR, 0.88; 95% CI, 0.52-1.49; P = .69). The overall standardized change score was 0.19 in the off-pump vs 0.12 in the on-pump group (P = .09). No statistically significant differences were observed between the on-pump and off-pump groups in quality of life, stroke rate, or all-cause mortality at 3 and 12 months. Conclusion  Patients who received their first CABG surgery without cardiopulmonary bypass had improved cognitive outcomes 3 months after the procedure, but the effects were limited and became negligible at 12 months.      

Birth weight and perinatal mortality: a comparison of "optimal" birth weight in seven Western European countries

BACKGROUND: Previous studies have suggested that a population's entire birth weight distribution may be shifted towards higher or lower birth weights, and that optimal birth weight may be lower in populations with a lower average birth weight. We evaluated this hypothesis for seven western European countries. METHODS: We obtained data on all singleton births (N = 1,372,092) and extended perinatal deaths (stillbirths plus neonatal deaths; N = 7,900) occurring in Finland, Sweden, Norway, Denmark, Scotland, the Netherlands, and Flanders (Belgium) in 1993-1995. We assessed whether countries differed in the mode of their birth weight distribution and in the birth weight associated with the lowest perinatal mortality, and then correlated the two. RESULTS: Substantial international differences were found in the mode of the birth weight distribution, which ranged between 3384 gm in Flanders and 3628 gm in Finland. The position of the minimum of the perinatal mortality curve also differed considerably, ranging between 3755 gm in Flanders and 4305 gm in Norway. There was a strong relation between the two: for every 100 gm increase in modal birth weight, optimal birth weight was 170 gm higher (95% confidence interval = 104-236 gm). CONCLUSIONS: Our results confirm those of previous studies that compared two populations. To improve the identification of small babies at high risk of perinatal death, population-specific standards for birth weight should be developed and used.     

Ageing and diabetes: implications for brain function

Polymorphisms of the renin-angiotensin system are associated with cardiovascular disorders, possibly as a consequence of increased brain angiotensin II activity. Within the brain, angiotensin controls blood pressure, fluid balance and hormone secretion; it also influences behaviour: reduction of central angiotensin function has both antidepressant-like and axiolytic-like actions. Evidence concerning the role of the renin-angiotensin system in learning and memory is contradictory, although more studies support the proposal that angiotensin reduces cognitive function. Studies of renin-angiotensin system genotype and psychological status have suggested an association between the angiotensin-converting enzyme deletion allele and age related cognitive decline, but a greater prevalence of the insertion allele in Alzheimer's disease. The deletion allele has also been associated with depressive illness, as has the M allele of the angiotensinogen gene although other studies have failed to replicate these findings. The role of the brain renin-angiotensin system in human psychopathology remains to be fully explored.