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A coal-derived sodium humate (HANa) was found to stimulate root growth of wheat seedlings ( Triticum aestivum L.). A study of possible modes of action of HANa showed that (i) by chelating out ferrous iron, HANa sequestered a key participant from the reaction whereby proline is hydroxylated to hydroxyproline, resulting in significantly less hydroxyproline being formed in the cell walls of roots treated with HANa, and that (ii) HANa inhibited the activity of peroxidase and IAA oxidase, the inhibition of peroxidase being of the uncompetitive type. Since these effects have implications for the ability of root cells to undergo extension, it is proposed that they provide explanations for the stimulatory effect of HANa on growth.

Of fifteen isolates of yeasts, filamentous fungi and bacteria and a commercial product, tested in a bioassay with stem segments, eleven isolates consistently reduced incidence of disease and sporulation of Botrytis cinerea Pers; Fr in tomato and seven isolates in cucumber. Several isolates reduced disease by more than 75% in all experiments. Six antagonists that performed well in the bioassays and that were fairly easy to produce in vitro, were selected for further testing in two glasshouse experiments with cucumbers. After application of spores of B. cinerea and the antagonists or the fungicide tolylfluanid to pruning wounds, disease incidence was reduced by 50–100% by all antagonists in both experiments and only in one experiment by tolylfluanid.

This study shows that consumption of fermented lactotripeptides (LTPs)-containing milk may have an acute daytime effect on blood pressure that appeared sustained with daily intake over a period of 4 weeks. Angiotensin 1-converting enzyme (ACE) inhibition by LTPs could not be confirmed in plasma.

The effect of vitamins and minerals enriched milk on blood pressure in mildly hypertensive subjects

Contains fulltext : 118070.pdf (Publisher’s version ) (Open Access) Statins are thought to reduce vascular inflammation through lipid independent mechanisms. Evaluation of such an effect in atherosclerotic disease is complicated by simultaneous effects on lipid metabolism. Abdominal aortic aneurysms (AAA) are part of the atherosclerotic spectrum of diseases. Unlike atherosclerotic occlusive disease, AAA is not lipid driven, thus allowing direct evaluation of putative anti-inflammatory effects. The anti-inflammatory potency of increasing doses (0, 20 or 40 mg/day) simvastatin or atorvastatin was evaluated in 63 patients that were at least 6 weeks on statin therapy and who underwent open AAA repair. A comprehensive analysis using immunohistochemistry, mRNA and protein analyses was applied on aortic wall samples collected during surgery. The effect of statins on AAA growth was analyzed in a separate prospective study in incorporating 142 patients. Both statins equally effectively and dose-dependently reduced aortic wall expression of NFkappaB regulated mediators (i.e. IL-6 (P

Item does not contain fulltext The transinguinal preperitoneal (TIPP) technique using a soft mesh with a memory ring was developed recently for inguinal hernia repair. To compare TIPP with the Lichtenstein method, a randomised trial was conducted (ISRCTN93798494). The aim of this study was to perform an economic evaluation of the TIPP modality compared to the Lichtenstein modality from both a hospital and societal perspective alongside the clinical trial. The TULIP study was a double-blind randomised clinical trial comparing two techniques for inguinal hernia repair (TIPP and Lichtenstein). Correct generation of the allocation sequence, allocation concealment, blinding, and follow-up were used/applied according to the recommendations of the Cochrane Handbook. Next to the cost drivers, the short-form-36 health survey (SF-36) data from the TULIP trial was used to determine utility. The SF-36 data from the TULIP trial were revised using the SF-6D algorithm according to Brazier. Two scenarios-a hospital and a societal perspective-were presented. If the analyses showed no difference in effects (on the SF-6D) the cost effectiveness decision rule to cost minimisation was altered. No significant difference in SF-6D utility between both modalities was found (mean difference: 0.888, 95 % CI -1.02 to 1.23); consequently, the economic decision rule became cost minimisation. For the hospital perspective no significant differences in costs were found (mean difference: -13, 95 % CI -130 to 104). However, when including productivity gains in the analysis, significant differences (P = 0.037) in costs favouring the TIPP modality (mean saving: 1,472, 95 % CI 463-2,714) were found. The results show that TIPP is a cost-saving inguinal hernia repair technique compared to the Lichtenstein modality against equal effectiveness expressed as quality adjusted life week at 1 year given a societal perspective. In the trial, TIPP patients showed on average a quicker recovery of 6.5 days compared to Lichtenstein patients.

Contains fulltext : 117847.pdf (Publisher’s version ) (Open Access) BACKGROUND: Lichtenstein's technique is considered the reference technique for inguinal hernia repair. Recent trials suggest that the totally extraperitoneal (TEP) technique may lead to reduced proportions of chronic pain. A systematic review evaluating the benefits and harms of the TEP compared with Lichtenstein's technique is needed. METHODOLOGY/PRINCIPAL FINDINGS: The review was performed according to the 'Cochrane Handbook for Systematic Reviews'. Searches were conducted until January 2012. Patients with primary uni- or bilateral inguinal hernias were included. Only trials randomising patients to TEP and Lichtenstein were included. Bias evaluation and trial sequential analysis (TSA) were performed. The error matrix was constructed to minimise the risk of systematic and random errors. Thirteen trials randomized 5404 patients. There was no significant effect of the TEP compared with the Lichtenstein on the number of patients with chronic pain in a random-effects model risk ratio (RR 0.80; 95% confidence interval (CI) 0.61 to 1.04; p = 0.09). There was also no significant effect on number of patients with recurrences in a random-effects model (RR 1.41; 95% CI 0.72 to 2.78; p = 0.32) and the TEP technique may or may not be associated with less severe adverse events (random-effects model RR 0.91; 95% CI 0.73 to 1.12; p = 0.37). TSA showed that the required information size was far from being reached for patient important outcomes. CONCLUSIONS/SIGNIFICANCE: TEP versus Lichtenstein for inguinal hernia repair has been evaluated by 13 trials with high risk of bias. The review with meta-analyses, TSA and error matrix approach shows no conclusive evidence of a difference between TEP and Lichtenstein on the primary outcomes chronic pain, recurrences, and severe adverse events.

The predaceous efficacy of five nematophagous fungi was investigated against the predaceous soil nematode, Butlerius sp., and the saprophagous nematode, Panagrolaimus sp., during the cultivation of the commercial mushroom, Agaricus bisporus. Two isolates, Arthrobotrys oligaspora and Dactylaria scaphoides, produced three dimensional adhesive networks in the isolation of other predatory organs, while Dactylaria dasguptae, an unidentified Dactylella species and the egg-parasitizing fungus, Dactylella oviparasitica, produced both networks and detachable knobs in the presence of nematodes under our experimental conditions. Preliminary studies in soil microhabitats proved A. oligospora and the unidentified Dacylalla species to be potentially effective biological control agents, immobilizing 80% of the total nematode population. However, during the cultivation of A. bisporus, the most biologically effective fungus, Dactylaria dasguptae, reduced the nemtode population by 35%. There is some evidence to suggest that saprophytic nematophagous fungi would make effective biocontrol agents.

A survey of the germination performance of some South African soya bean [Glycine max (L.) Merrill.] cultivars, produced at different localities, was conducted. Seeds were harvested from two early-maturing (Columbus and Crawford), two intermediate-maturing (Prima and Highveld Top), and two late-maturing cultivars (Ibis and Impala), from seven sites. The standard germination test was performed on all 42 seed lots. Germination performance was not linked to any particular maturity type or cultivar, but locality had a distinct effect. Germination of seeds of some seed lots harvested at Groblersdal and Potchefstroom was reduced, primarily due to the effect of seed-borne pathogens, which resulted in relatively large numbers of dead seeds. At Piet Retief, poor germination performance was inversely related to the large number of abnormal seedlings in the standard germination test, which was due to damaged seed coats. There were highly significant correlations between the number of dead seeds and the incidence of f...

Background Rapid ventricular pacing reduces the incidence of ventricular arrhythmias during a subsequent sustained period of ischemia and reperfusion. We investigated whether rapid ventricular pacing also limits myocardial infarction and determined the role of K ATP + channels in the protection afforded by ventricular pacing. Methods and Results Myocardial infarction was produced by a 60-minute coronary artery occlusion in open chest pigs. Infarct size of pigs subjected to 10 minutes of ventricular pacing at 200 beats per minute followed by 15 minutes of normal sinus rhythm before the occlusion (79±3% of the area at risk, mean±SEM) was not different from control infarct size (84±2%). Thirty-minute pacing followed by 15-minute sinus rhythm resulted in modest reductions in infarct size (71±2%, P P ATP + channel blocker glibenclamide (78±4%, P =NS). K ATP + channel activation did not appear to involve ischemia: (1) myocardial endocardial/epicardial blood flow ratio was 1.07±0.08, (2) phosphocreatine and ATP levels and arterial-coronary venous differences in pH and P co 2 were unchanged, (3) end-systolic segment length did not increase and postsystolic shortening was not observed during pacing, and (4) systolic shortening recovered immediately to baseline levels and coronary reactive hyperemia was absent after cessation of pacing. Administration of glibenclamide after 30 minutes of pacing at the onset of 15 minutes of normal sinus rhythm did not attenuate the protection (73±3%, P ATP + channels did not contribute to the moderate degree of protection that was still present 15 minutes after cessation of pacing. Conclusions Rapid ventricular pacing protects the myocardium against infarction via nonischemic K ATP + channel activation. Continued activation of K ATP + channels does not appear mandatory for the protection that is still present 15 minutes after cessation of pacing.

Objective: Recently, we reported that a partial coronary artery occlusion immediately preceding a sustained coronary artery occlusion limited infarct size. We now investigated whether the protection by partial coronary artery occlusions (i) depends on the severity and(or) duration of the flow reduction and (ii) varies in the different myocardial layers. Methods: In 71 open-chest pigs (eight groups) left ventricular area at risk (AR) and infarct area (IA) were determined for the endocardial (IAendo and ARendo) and epicardial halves (IAepi and ARepi). Results: In control animals (60 min total coronary artery occlusion (TCO) followed by 120 min reperfusion (Rep)) there were highly linear relations between LA and AR in the endocardium ( r = 0.98, P < 0.01) and epicardium ( r = 0.97, P < 0.01), which could be described by IAendo = 1.01ARendo − 4.5 and by IAepi = 0.88ARepi − 3.6, respectively. In animals that underwent a 10 min TCO + 15 min Rep prior to the 60 min TCO + 120 min Rep, IA in both myocardial layers were again highly linearly related with AR, with less steep slopes for both the endocardium (0.63) and epicardium (0.57) (both P < 0.01). Two groups of pigs were subjected to either a 30 or 90 min 70% reduction in coronary blood flow (FR) immediately preceding the 60 min TCO + 120 min Rep, without intervening reperfusion. A 30 min 70% FR decreased IA to the same degree in the endo- and epicardial half. A 90 min 70% FR resulted in protection in the epicardium ( P < 0.01) but not in the endocardium, most likely because 90 min 70% FR without 60 min TCO already caused infarction which was more severe in the endo- than in the epicardium ( P < 0.01). Endocardial and epicardial IA after either a 30 or 90 min 30% FR prior to the 60 min TCO was not different from that in the control group, indicating that this mild flow reduction failed to limit irreversible damage. Conclusions: Thirty or ninety min of severe (70%) but not mild (30%) coronary flow reductions protected against myocardial infarction. The protection by a 70% FR was influenced by the duration of FR as a 30 min 70% FR similarly decreased IA in the endocardial and epicardial halves, while 90 min 70% FR preferentially limited IA in the epicardial half. These findings suggest that perfusion abnormalities immediately preceding an infarction could be an important source of infarct size variability in patients.

Item does not contain fulltext INTRODUCTION: Laparoscopic and endoscopic hernia repair popularized the preperitoneal mesh position due to promising results concerning less chronic pain. However, considerable proportions of severe adverse events, learning curves, or added costs have to be taken into account. Therefore, open preperitoneal mesh techniques may have more advantages. The open approach to the preperitoneal space (PPS) according to transrectus sheath preperitoneal (TREPP) mesh repair is through the sheath of the rectus abdominus muscle. This technique provides an excellent view of the PPS and facilitates elective or acute hernia reduction and mesh positioning under direct vision. In concordance with the promising transinguinal preperitoneal inguinal hernia repair experiences in the literature, we investigated the feasibility of TREPP. METHODS: A rationale description of the surgical technique, available level of evidence for thoughts behind technical considerations. Furthermore, a descriptive report of the clinical outcomes of our pilot case series including 50 patients undergoing the TREPP mesh repair. RESULTS: A consecutive group of our first 50 patients were operated with the TREPP technique. No technical problems were experienced during the development of this technique. No conversions to Lichtenstein repair were necessary. No recurrences and no chronic pain after a mean follow-up of 2 years were notable findings. CONCLUSION: This description of the technique shows that the TREPP mesh repair might be a promising method because of the complete preperitoneal view, the short learning curve, and the stay-away-from-the-nerves principle. The rationale of the TREPP repair is discussed in detail. 01 juni 2012

Background Preliminary experience has suggested that preperitoneal mesh positioning causes less chronic pain than Lichtenstein's technique for inguinal hernia repair. Therefore, a randomized clinical trial was conducted with the aim of evaluating the incidence of postoperative chronic pain after transinguinal preperitoneal (TIPP) mesh repair versus Lichtenstein's technique. Methods Patients with a primary unilateral inguinal hernia were randomized to either TIPP or Lichtenstein's repair in two training hospitals. The primary outcome was the number of patients with chronic pain after surgery. Secondary outcomes were adverse events. Follow-up was scheduled after 14 days, 3 months and 1 year. Patients and outcome assessors were blinded. Results A total of 302 patients were randomized to TIPP (143) or Lichtenstein (159) repair. Baseline characteristics were comparable in the two groups. Some 98·0 per cent of the patients were included in the analysis (141 in the TIPP group and 155 in the Lichtenstein group). Significantly fewer patients in the TIPP group had continuous chronic pain 1 year after surgery: five patients (3·5 per cent) versus 20 patients (12·9 per cent) in the Lichtenstein group (P = 0·004). An additional 12 patients (8·5 per cent) in the TIPP group and 60 (38·7 per cent) in the Lichtenstein group experienced pain during activity (P = 0·001). There were two patients with recurrence in the TIPP group and four in the Lichtenstein group, but no significant differences were found in other severe adverse events between the groups. Conclusion Fewer patients had continuous chronic pain at 1 year after the TIPP mesh inguinal hernia repair compared with Lichtenstein's repair. Registration number: ISRCTN93798494 (http://www.controlled-trials.com).

Objective: The aim was to investigate whether ischaemic preconditioning can be obtained by a partial coronary artery occlusion without intermittent reperfusion. Methods: In seven anaesthetised open chest pigs, the flow in the proximal left anterior descending coronary artery was reduced to 30% of baseline during 30 min before the vessel was occluded completely for 60 min (60 min total coronary occlusion, TCO). After 2 h of reperfusion, the area at risk (AR) and infarct size (IS) were determined using standard procedures. Infarct sizes were compared to those observed in control animals (n = 12), which were subjected to 60 min TCO and 2 h reperfusion, and to infarct sizes determined in animals preconditioned by 10 min TCO with either 15 min (n = 10) or 60 min (n = 5) of reperfusion before the 60 min TCO and 2 h reperfusion. In the last three groups of animals, area at risk was varied by occluding the coronary artery or its branches at different sites. Results: In the control animals infarct size was linearly related (r = 0.99, p< 0.001) to the area at risk with a positive intercept on the AR axis: IS/LVmass (×100%) = 0.88 AR/LVmass (×100%)−3.6. At comparable areas at risk, the infarct size of the animals preconditioned with a 10 min TCO was less than for the control animals. For the animals preconditioned with 10 min TCO and 15 min reperfusion, the relationship between infarct size and area at risk was again linear (r = 0.88) and also had a positive intercept on the AR axis: IS/LVmass (× 100%) = 0.68 AR/LVmass (× 100%)-4.8. All animals with the flow reduction to 30% of baseline immediately preceding the 60 min TCO had infarct sizes smaller (p < 0.05) than predicted from the regression equation for the control animals, but the infarct size limitation could not be simply related to variables such as changes in regional systolic and postsystolic segment length shortening, ATP, or ADP during the partial occlusion period. Conclusions: Myocardium can be preconditioned with a flow reduction to 30% of baseline for 30 min without intermittent reperfusion (two stage Harris model). The positive intercept on the AR axis of the IS-AR relationship warrants caution of the use of IS/AR as an index for infarct size limitation. Cardiovascular Research 1994; 28 :1146-1151

We evaluated the effect of trimetazidine (TMZ) on recovery of regional cardiac function in anesthetized open-chest pigs, subjected to fifteen 2-minute occlusions of the left anterior descending coronary artery, separated by 2 minutes of reperfusion and a 120-minute recovery period. Regional myocardial function was evaluated by sonomicrometry-derived segment lengthening and the area enclosed by the left ventricular pressure-segment length loop (external work, EW) in animals, which received either an intracoronary infusion of TMZ (33 µg/kg/min, n=6) or saline (1 ml/min, n=7), starting 15 minutes before the first occlusion and ending 2 minutes after the 15th occlusion. In addition, myocardial malondialdehyde production to evaluate oxygen free radical production, oxygen consumption, and the ATP, ADP, and AMP content, as well as the energy charge, were determined at regular time intervals. In control pigs the sequences of occlusion-reperfusion did not affect systemic hemodynamics, except for the LVdP/dtmax, which decreased by 11% during the interventions and did not recover during the following reperfusion period of 2 hours (78% of baseline, p

We report a rapid breakdown of dopamine and especially of 3,4-dihydroxybenzylamine, the frequently-used internal standard in catecholamine determinations, in plasma of many but not all animal species. Species investigated were cow, sheep, goat, pig, horse, rabbit, dog, guinea pig, mouse, chicken, rat and man. In some species 3,4-dihydroxybenzylamine nearly completely disappeared at 4 degrees C within 15 min after addition to the plasma. Added dopamine, but not norepinephrine and epinephrine, also rapidly disappeared at 4 degrees C. Disappearance rates were increased at higher temperatures, and at 20 degrees C also norepinephrine showed some breakdown. The breakdown is caused by a semicarbazide-sensitive amine oxidase in the plasma, and can be completely blocked by the addition of the inhibitor semicarbazide. Measurement of plasma catecholamine concentrations in animal species can thus lead to erroneous results, especially when 3,4-dihydroxybenzylamine is used as an internal standard. Only when blood is collected in tubes containing an inhibitor of semicarbazide-sensitive amine oxidase like semicarbazide can reliable plasma catecholamine measurements be performed.

To estimate the contribution of angiotensin (ANG) I and II production at tissue sites to the circulating levels, ANG I and II and their radiolabeled counterparts were measured in arterial and venous plasma across various vascular beds during constant infusion of 125I-ANG I into the left cardiac ventricle of anesthetized pigs. In the combined systemic vascular beds, ANG I production was closely correlated with plasma renin activity (PRA) and ANG II production was greater than in the lungs. In the lungs virtually no ANG I but 31% of ANG II in venous plasma was derived from de novo production, which could be fully accounted for by conversion of circulating ANG I. In myocardium, head, skin, skeletal muscle, and kidney, respectively, 40, 58, 55, 67, and 94% of venous ANG I, and 32, 49, 40, 59, and 85% of venous ANG II were derived from de novo production. In these extrapulmonary beds part of de novo produced ANG I and II appeared not to be generated, respectively, by PRA and by conversion of circulating ANG I. These results indicate that production of ANG I at tissue sites contributes to its circulating level and that some circulating ANG II may not be derived from circulating ANG I.

The effects of stepwise isovolemic hemodilution on systemic and regional hemodynamics, oxygen flux, and circulating catecholamines were studied in six pigs anesthetized with midazolam and fentanyl. Reduction of the hematocrit from 28 to 9% resulted in doubling of the cardiac output, mainly due to an increase in stroke volume. Regional blood flows, measured using the radioactive microsphere technique, showed an increase in blood flow to all organs except liver (hepatic artery fraction) and adrenals, with a redistribution of cardiac output in favor of heart and brain (increase in blood flow 420 and 170%, respectively). Oxygen flux to most organs did not decrease until hematocrit decreased to 9%, while total body oxygen consumption was well maintained. Left ventricular oxygen consumption increased, but because left ventricular blood flow also increased, left ventricular extraction ratio did not increase. Circulating catecholamines did not play any role in these regulatory mechanisms.

Background Anterior open treatment of the inguinal hernia with a tension free mesh has reduced the incidence of recurrence and direct postoperative pain. The Lichtenstein procedure rules nowadays as reference technique for hernia treatment. Not recurrences but chronic pain is the main postoperative complication in inguinal hernia repair after Lichtenstein's technique. Preliminary experiences with a soft mesh placed in the preperitoneal space showed good results and less chronic pain. Methods The TULIP is a double-blind randomised controlled trial in which 300 patients will be randomly allocated to anterior inguinal hernia repair according to Lichtenstein or the transinguinal preperitoneal technique with soft mesh. All unilateral primary inguinal hernia patients eligible for operation who meet inclusion criteria will be invited to participate in this trial. The primary endpoint will be direct postoperative- and chronic pain. Secondary endpoints are operation time, postoperative complications, hospital stay, costs, return to daily activities (e.g. work) and recurrence. Both groups will be evaluated. Success rate of hernia repair and complications will be measured as safeguard for quality. To demonstrate that inguinal hernia repair according to the transinguinal preperitoneal (TIPP) technique reduces postoperative pain to Discussion The TULIP trial is aimed to show a reduction in postoperative chronic pain after anterior hernia repair according to the transinguinal preperitoneal (TIPP) technique, compared to Lichtenstein. In our hypothesis the TIPP technique reduces chronic pain compared to Lichtenstein. Trial registration ISRCTN 93798494

Clinical studies have demonstrated a beneficial effect on blood pressure for milk derived material containing isoleucyl-prolyl-proline (IPP) and valine-prolyl-proline (VPP) peptides. The aim of the present study was to evaluate the blood pressure lowering effect of three different IPP and VPP doses in products with a comparable electrolyte and protein composition. The present study was designed as a randomized, double-blind, parallel-group, dose-response trial: 166 subjects (140/90 mmHg) received placebo during a 2-week run-in, 8-weeks intervention followed by a 2-week washout. Results indicate that materials containing IPP and VPP do lower blood pressure dose-dependently (p0.05 for diastolic blood pressure, DBP). The effect on systolic blood pressure (SBP)/DBP over 8 weeks compared with placebo was + 0.1/- 1.3, - 1.5/- 1.4 and - 2.5/- 1.9 mmHg for the low, medium and high dose of peptides, respectively. The percentages of subjects who showed a fall in SBP3 mmHg or who attained an SBP below 140 mmHg, were 54% (placebo), 64% (low), 76% (medium) and 71% (high dose) respectively. This effect can only be demonstrated for office pressure and not for home or ambulatory pressure. Furthermore, the results suggest that the magnitude of the fall in blood pressure is a function of baseline blood pressure. We conclude that IPP and VPP may have a modest dose-dependent effect on office blood pressure in mildly hypertensive subjects although this could not be confirmed with ambulatory or home blood pressure measurements.

NMR structures of biomolecules are primarily based on nuclear Overhauser effects (NOEs) between protons. For the interpretation of NOEs in terms of distances, usually the assumption of a single rotational correlation time corresponding to a rigid molecule approximation is made. Here we investigate the effect of fast internal motions of the interproton vectors in the context of the relaxation matrix approach for structure determination of biomolecules. From molecular dynamics simulations generalized order parameters were calculated for the DNA octamer d(GCGTTCGC).d(CGCAACGC), and these were used in the calculation of NOE intensities. The magnitudes of the order parameters showed some variation for the different types of interproton vectors. The lowest values were observed for the interresidue base H6/H8-H2" proton vectors (S2 = 0.60), while the cytosine H5-H6 interproton vectors were among the most motionally restricted (S2 = 0.92). Inclusion of the motion of the interproton vectors resulted in a much better agreement between theoretically calculated NOE spectra and the experimental spectra measured by 2D NOE spectroscopy. The interproton distances changed only slightly, with a maximum of 10%; nevertheless, the changes were significant and resulted in constraints that were better satisfied. The structure of the DNA octamer was determined by using restrained molecular dynamics simulations with H2O as a solvent, with and without the inclusion of local internal motions. Starting from A- or B-DNA, the structures showed a high local convergence (0.86 A), while the global convergence for the octamer was ca. 2.6 A.

A 39-year-old woman had a car crash. The normal anatomical lines in the left carpometacarpal joints were no longer visible on X-ray: the hand equivalent of the Lisfranc luxation in the foot.

Methods for calculation of NOE intensities of proton pairs on molecules where internal motion occurs are discussed in the framework of the full-relaxation-matrix approach. Model systems mimicking 180° flips of aromatic rings and methyl group rotation are considered. The simultaneous effect of these dynamic processes and that of spin diffusion can be described in two ways: the first is to add a kinetic matrix to the relaxation matrix and the second involves a weighted average of the relaxation-matrix elements. For motions that are fast compared to the correlation time for molecular tumbling such as methyl group rotation the individual proton-proton vectors are averaged as 〈 r −3 〉 and the appropriate spectral density functions need to be used. The effect of motion on the back transformation from NOE intensities to proton-proton distances has also been examined for these model systems. Since inclusion of motion results in averaging of intensities, pseudoatom corrections on the determined distances are usually needed. It is shown that in the case of the rotating methyl group 〈 r −3 ) averaging leads to a pseudoatom correction of only 0.3 A rather than the often used 1.0 A.

1. The central and regional cardiovascular responses to intravenous (0.3, 1.0, 3.0 and 10.0 micrograms kg-1 min-1) and intracoronary (0.3, 0.9, 3.0 and 4.5 micrograms kg-1 min-1) infusions of elgodipine, a phenyldihydropyridine, and its solvent were studied in anaesthetized pigs. 2. Elgodipine (i.v.) caused dose-dependent decreases in arterial blood pressure (up to 44%) and systemic vascular resistance (up to 48%), whereas heart rate, LV dP/dtmax, left ventricular filling pressure, cardiac output and segment length shortening did not change. The absence of a negative inotropic effect with the employed doses was confirmed by the intracoronary infusions; with the lowest dose (0.3 micrograms kg-1 min-1) both LV dP/dtmax and segment length shortening decreased by less than 10%. With 0.9 micrograms kg-1 min-1 (intracoronary) the negative inotropic properties of the drug became apparent as LV dP/dtmax and segment length shortening decreased by 20% and 33%, respectively, whereas heart rate and left ventricular filling pressure were not affected. 3. Transmural myocardial blood flow did not change during intravenous infusion of elgodipine, as vasodilatation, more pronounced in the subepicardial than in the subendocardial layers, compensated for the decrease in arterial perfusion pressure. The intracoronary infusions revealed that the decrease in normalized subendocardial/subepicardial blood flow ratio was not secondary to the fall in arterial blood pressure. 4. Myocardial oxygen consumption decreased during both the i.v. and the intracoronary administration of elgodipine. With the i.v. administration the decrease was secondary to the hypotensive action of the drug, whereas with the intracoronary administration the negative inotropic properties played the dominant role. 5. Elgodipine (i.v.), although not affecting total cardiac output, caused a redistribution in favour of the nutritional blood flow at the expense of the arteriovenous anastomotic (AVA) blood flow. Up to an infusion rate of 3.0upg kg - I min- 1 the decrease in AVA-flow was due to a fall in arterial blood pressure, but at the highest infusion rate both the decrease in arterial perfusion pressure and an increase in their resistance contributed to a further decrease in AVA blood flow. 6. The skeletal muscles benefited most from the elgodipine(i.v.)-induced increase in nutritional blood flow, but vasodilatation was not uniform for all muscle groups. Up to an infusion rate of 3 yg kg - ' min- 1 the vasodilatation in the renal vascular bed was more pronounced in the inner than in the outer cortex, but, at 0 pyg kg-1 min-, vascular resistances of both cortical layers returned to baseline values. In all regions of the brain, blood flow was maintained until the highest infusion rate was given. With 10 yg kg- I min - ' only flow to the vital parts of the brain (diencephalon and brain stem) was maintained. Blood flows to the skin and various abdominal organs were well maintained up to 3 pg kg'- min - 1 but, at the highest dose, a decrease was observed in blood flow to the adrenals and spleen. Vascular resistances of all these organs and tissues decreased dose-dependently. 7. The potent systemic and coronary vasodilator actions of elgodipine during i.v. administration, which were not accompanied by negative inotropic and positive chronotropic properties or decreases in the perfusion of vital organs, warrant further study as this compound could be useful in the treatment of essential hypertension, myocardial ischaemia and, possibly, moderate chronic heart failure.

Nuclear magnetic resonance (NMR) and model-building studies were carried out on the hairpin form of the octamer d(CGaCTAGCG) (aC = arabinofuranosylcytosine), referred to as the TA compound. The nonexchangeable protons of the TA compound were assigned by means of nuclear Overhauser effect spectroscopy (NOESY) and correlated spectroscopy (COSY). From a detailed analysis of the coupling data and of the NOESY spectra the following conclusions are reached: (i) The hairpin consists of a stem of three Watson-Crick type base pairs, and the two remaining residues, T(4) and dA(5), participate in a loop. (ii) All sugar rings show conformational flexibility although a strong preference for the S-type (C2'-endo) conformer is observed. (iii) The thymine does not stack upon the 3' side of the stem as expected, but swings into the minor groove. (This folding principle of the loop involves an unusual alpha t conformer in residue T(4).) (iv) At the 5'-3' loop-stem junction a stacking discontinuity occurs as a consequence of a sharp turn in that part of the backbone, caused by the unusual beta + and gamma t torsion angles in residue dG(6). (v) The A base slides over the 5' side of the stem to stack upon the aC(3) residue at the 3' side of the stem in an antiparallel fashion. On the basis of J couplings and a set of approximate proton-proton distances from NOE cross peaks, a model for the hairpin was constructed. This model was then refined by using an iterative relaxation matrix approach (IRMA) in combination with restrained molecular dynamics calculations. The resulting final model satisfactorily explains all the distance constraints.

Food products containing angiotensin converting enzyme (ACE) inhibitory peptides reportedly play a role in treatment of mild hypertension. The aim of this placebo-controlled crossover study was to assess the bioavailability of Ile-Pro-Pro and 7 other ACE-inhibiting peptides present in a lactotripeptide (LTP)-enriched yogurt beverage and whether meal intake affects Ile-Pro-Pro bioavailability. Six male and female subjects randomly consumed an LTP-enriched yogurt beverage or a placebo in the fasted state and an LTP-enriched yogurt beverage in the fed or fasted state. The area under the curve (AUC) of Ile-Pro-Pro after the LTP treatment in the fasted state was 2.1-fold of that after the placebo treatment (P0.001). The maximum peptide plasma concentration (C(max)) value was greater after consumption of the LTP-enriched beverage (897 +/- 157 pmol/L) than after the placebo treatment (555 +/- 0.09 pmol/L; P0.001) with a greater time after ingestion when reaching C(max) (T(max)) in the placebo treatment. Plasma concentrations of the peptides Leu-Trp, Phe-Tyr, Ile-Tyr, and Leu-Pro-Pro increased compared with baseline (P0.05) in the LTP-enriched and placebo treatment when consumed in the fasted state. However, DeltaC(max) values differed significantly between the placebo and LTP-enriched treatment only for Leu-Pro-Pro. Meal intake affected Ile-Pro-Pro concentrations. When the beverage was consumed after a meal, the AUC of Ile-Pro-Pro was 1.3-fold (P0.05) of the AUC derived from premeal intake. This was due to an increase in the plasma elimination half-life (P0.05); C(max) and T(max) were not affected by meal intake. In summary, this is the first demonstration, to our knowledge, that the tripeptide Ile-Pro-Pro selectively escapes from intestinal degradation and reaches the circulation undegraded.

OBJETIVO: Este estudo observacional foi desenvolvido para pesquisar a influência dos medicamentos na ocorrência de complicações após correção endovascular de aneurismas da aorta abdominal. MÉTODO: Foram analisados retrospectivamente os dados clínicos referentes a 70 pacientes consecutivos submetidos à correção endovascular de aneurisma da aorta abdominal em dois centros cirúrgicos vasculares num período de 3 anos. As complicações eram classificadas de acordo com as recomendações do Comitê Designado de Padrões de Tratamento. Foi feita uma distinção entre complicações relacionadas ou não ao stent. Uma análise de regressão foi usada para avaliar a associação entre 12 grupos de medicamentos diferentes e o resultado da correção endovascular. RESULTADOS: Durante um acompanhamento de 70 pacientes-anos, foram relatadas 14 complicações leves (20%), 23 moderadas (33%) e sete graves (10%). Trinta pacientes (43%) que usaram cumarínicos tiveram significantemente menos complicações não relacionadas ao stent (OR. 0,21; 95% CI 0,05-0,90) comparados com os não usuários. Vinte pacientes (29%), tomando medicamentos antieméticos durante internação, mostraram quatro vezes mais complicações relacionadas ao stent (OR. 4,37; 95% CI 1,10-17,3) e o uso de analgésicos no hospital em 25 pacientes foi associado com mais complicações relacionadas ao stent (OR. 3,81; 95% CI 1,32-11,0). CONCLUSÃO: Medicações parecem estar associados com a ocorrência de complicações após terapia endovascular de aneurismas da aorta abdominal. Pacientes que usaram cumarínicos tiveram menos complicações não relacionadas ao stent. Pacientes que usaram agentes antieméticos durante internação mostraram um número quatro vezes maior de complicações não relacionadas ao stent. Pacientes usando analgésicos durante a internação eram associados com maiores complicações relacionadas ao stent. OBJECTIVE: This observational study was undertaken to explore the influence of medication on the occurrence of complications following endovascular repair of abdominal aortic aneurysms. METHODS: Clinical data concerning 70 consecutive patients undergoing elective EVAR in two vascular surgical centres over a 3 year period were analysed retrospectively. Complications were graded according to the recommendations of the Ad Hoc Committee on Reporting Standards. A distinction was made between device-related and non-related complications. An adjusted regression analysis was used to assess the association between 12 different medication groups and EVAR outcome. RESULTS: During 70 person years of follow-up 14 mild (20%), 23 moderate (33%) and 7 severe (10%) complications were recorded. Thirty patients (43%) who used coumarin derivates showed significantly less non-device-related complications (OR 0.21; 95%CI 0.05-0.90) compared to non-users. Twenty patients (29%) on anti-emetic drugs during hospital stay showed a fourfold more non-device-related complications (OR 4.37; 95%CI 1.10-17.3) and in-hospital use of analgesics in 25 patients was associated with more device-related complications (OR 3.81; 95%CI 1.32-11.0). CONCLUSION: Medication seems to be associated with the occurrence of complications following endovascular therapy of abdominal aortic aneurysms. Patients who used coumarin-derivatives experienced fewer non-device-related complications. Patients who used anti-emetic drugs during hospital-stay showed a fourfold number of non-device-related complications. Patients using analgesics during hospital stay were associated with significantly more device-related complications

For peacekeeping and peace enforcing missions abroad the Netherlands Armed Forces decided to use universal donor frozen blood products in addition to liquid products. This article describes our experiences with the frozen blood inventory, with special attention to quality control. It is shown that all thawed (washed) blood products are in compliance with international regulations and guidelines. By means of the -80 degrees C frozen stock of red cells, plasma and platelets readily available after thaw (and wash), we can now safely reduce shipments and abandon the backup 'walking' blood bank, without compromising the availability of blood products in theatre.

Automatic segmentation of the left ventricular (LV) myocardial borders in cardiovascular MR (CMR) images allows a significant speed-up of the procedure of quantifying LV function, and improves its reproducibility. The automated boundary delineation is usually based on a set of parameters that define the algorithms. Since the automatic segmentation algorithms are usually sensitive to the image quality and frequently depend heavily on the acquisition protocol, optimizing the parameters of the algorithm for such different protocols may be necessary to obtain optimal results. In other words, using a default set of parameters may be far from optimal for different scanners or protocols. For the MASS-software, for example, this means that a total of 14 parameters need to be optimized. This optimization is a difficult and labor-intensive process. To be able to more consistently and rapidly tune the parameters, an automated optimization system would be extremely desirable. In this paper we propose such an approach, which is based on genetic algorithms (GAs). The GA is an unsupervised iterative tool that generates new sets of parameters and converges toward an optimal set. We implemented and compared two different types of the genetic algorithms: a simple GA (SGA) and a steady state GA (2SGA). The difference between these two algorithms lies in the characteristics of the generated populations: "nonoverlapping populations" and "overlapping populations," respectively "nonoverlapping" population means that the two populations are disjoint, and "overlapping" means that the best parameters found in the previous generation are included in the present population. The performance of both algorithms was evaluated on twenty routinely obtained short-axis examinations (eleven examinations acquired with a steady-state free precession pulse sequence, and nine examinations with a gradient echo pulse sequence). The optimal parameters obtained with the GAs were used for the LV myocardial border delineation. Finally, the automatically outlined contours were compared to the gold standard--manually drawn contours by experts. The result of the comparison was expressed as a degree of similarity after a processing time of less than 72 h to a 59.5% of degree of similarity for SGA and a 66.7% of degree of similarity for 2SGA. In conclusion, genetic algorithms are very suitable to automatically tune the parameters of a border detection algorithm. Based on our data, the 2SGA was more suitable than the SGA method. This approach can be generalized to other optimization problems in medical image processing.

The potentisation process by which homeopathic preparations are produced raises the concern that these medicines have placebo effects only, since they theoretically no longer contain active molecules of the diluted substance. Plant models offer a method of examining the efficacy of homeopathically prepared solutions. This study examined the effects of homeopathically prepared gibberellic acid (HGA3) on the germination performance of barley (Hordeum vulgare L.) seeds. The effect of HGA3 (4-200 cH) on seed germination rate and seedling development was compared to that of the most commonly used form of gibberellic acid (GA3), 0.5 g l(-1), and control (distilled water). The extent and type of response was dependent on the vigour level of the seedlot. Treating seeds from three vigour groups in HGA3 consistently resulted in larger seedlings. High-vigour seeds treated with HGA3 4, 30 and 200 cH germinated faster, and roots of medium-vigour seedlots treated in HGA3 15 cH were longer. Biphasic effects of HGA3 were also demonstrated. As a plant model, germinating barley seeds successfully demonstrated the ability of HGA3 to produce a biological response.

BACKGROUND : RBCs can be frozen with either the high-glycerol method (HGM) or the low-glycerol method (LGM). To date, the use of frozen RBCs is hampered by a 24-hour outdating period after thawing. A closed washing system (ACP 215) may solve this problem. STUDY DESIGN AND METHODS : We compared the effects of high- (40%) and low-glycerol (19%) concentration, with and without freezing (at –80°C for HGM, –196°C for LGM) on the in vitro quality of RBCs after deglycerolization with the closed washing system and during storage at 4°C in SAGM after thawing. RESULTS : Glycerol treatment by itself induced hemolysis during processing, which was more pronounced in HGM cells. The freeze-thaw-wash process decreased the stability of RBCs, particularly in LGM cells during storage after thawing. In contrast to LGM cells, in HGM cells no additional effect of freeze or thaw on stability of washed cells was seen during the first week of storage after thawing. Changes in osmotic resistance and cellular metabolism could not explain the observed differences in RBC stability. CONCLUSION : The closed washing system is able to process both high- and low-glycerol-treated RBCs. Stability after washing during cold storage in SAGM, as measured by hemolysis, is better for HGM cells as compared to LGM cells.

An automated approach for the detection of the left ventricular outline in a selected frame is described. The system uses a combination of algorithms to detect a rough model of the left ventricular contour. The first algorithm, a pyramidal segmentation algorithm, segments the image into a relatively large number of homogeneous areas. The second algorithm uses a neural network to select the areas that most likely belong to the left ventricle. After model detection, the actual contour is found by dynamic programming. The position of the aortic valve is assessed from the shape of the detected contour. >

The automated segmentation of lumen, vessel and stent boundaries in intravascular ultrasound (IMS) images will reduce the required analysis time and the subjectivity of the commonly used manual tracing procedure while the three-dimensional reconstruction permits an advanced assessment of the morphology. We describe a knowledge and model guided system for the (semi-) automatic contour detection of these borders. The different steps of a complete analysis of an IVUS pullback sequence are carried out such, that the different components assist each other. The stent detection assists the vessel detection and both detections assist the lumen detection. The results of the detection show a very good correlation with manually drawn contours. Due to the flexible use of more than two longitudinal cut planes and the advanced knowledge-guided contour detection approach, the new IVUS analysis system has proven to be suitable for clinical research-studies.

Localization of target sites for radiofrequency catheter ablation (RFCA) is facilitated by the identification of abnormal electrograms at specific endocardial sites. With new 3-D electro-anatomical mapping systems such as the CARTO/sup TM/ system and the Real-time Positioning Management System/sup TM/ (RPM) the 3-D position of EP catheters can be visualized and recorded Detailed information about anatomical structures can only be obtained by standard imaging modalities, such as ventricular angiography. Combination of information obtained from the 3-D mapping systems with angiographic image information would therefore greatly enhance the applicability of these systems. In patients referred for ventricular tachycardia, the XYZ-coordinates of the ablation catheter positions, were obtained with the RPM system, and visualized in 3-D space. In addition, biplane angiographic images were obtained in these patients to confirm the geometric findings of the mapping system, and to display the ablation locations superimposed on the angiographic images. Analysis of the mapping and angiography data revealed that it is not feasible to create an accurate 3-D representation of a heart chamber based on two angiographic projections. Therefore, fusion of mapping data and angiographic images was not possible as planned. However, new ideas are presented that may make this fusion possible in the near future.

Introduction: An aortoduodenal fistula is a potentially lethal complication after transperitoneal open repair of an abdominal aortic aneurysm. Case Report: A 77-year-old Caucasian male who underwent a conventional repair of an inflammatory infrarenal aortic aneurysm, was readmitted with hematemesis only six weeks after surgery. Gastroscopy and computed tomography angiography indicated an aortoduodenal fistula and urgent aortic reconstruction was performed. An aortoduodenal fistula is a potentially lethal complication after transperitoneal open repair of an abdominal aortic aneurysm. Conclusion: An aortoduodenal fistula seldom occurs as early after conventional transperitoneal open aneurysm repair as in our case. The early occurrence of the aortoduodenal fistula can be explained by the inflammatory character of the aneurysm.

IntraVascular UltraSound (IVUS) is a catheter-based technique which provides real-time high resolution tomographic images of both the lumen and arterial wall of a coronary segment, this in contrast to X-ray arteriography that provides a shadow image (luminogram) of the entire lumen. Nowadays the lumen and vessel parameters are measured manually, which is very time consuming and suffers from high inter- and intra-obser variability. With the continuing improvement in IVUS imaging, it is now feasible to develop and clinically apply automated methods of three-dimensional quantitative analysis of the coronary vessel morphology in an objective and reproducible way with automated contour detection techniques (QCU). Quantification, in 2D and 3D, as well as volume rendering for visualization of the IVUS images requires segmentation of the images (contour detection). The 3D contour detection system described in this article is based on the combination of contour detection in the transversal and sagital view. This article provides some of the basic principles of IVUS, the IVUS image quantification, the three-dimensional reconstruction and the contour detection and quantification in three-dimensional IVUS images.

This report describes whether lossy Joint Photographic Experts Group (UPEG) image compression/decompression has an effect on the quantitative assessment of vessel sizes by state-of-the-art quantitative coronary arteriography (QCA).The Digital Imaging and Communications in Medicine (DICOM) digital exchange standard for angiocardiography prescribes that images must be stored loss free, thereby limiting JPEG compression to a maximum ratio of 2:1. For practical purposes it would be desirable to increase the compression ratio (CR), which would lead to lossy image compression.A series of 48 obstructed coronary segments were compressed/decompressed at CR 1:1 (uncompressed), 6:1, 10:1 and 16:1 and analyzed blindly and in random order using the QCA-CMS analytical software. Similar catheter and vessel start- and end-points were used within each image quartet, respectively. All measurements were repeated after several weeks using newly selected start- and end-points. Three different sub-analyses were carried out: the intra-observer, fixed inter-compression and variable inter-compression analyses, with increasing potential error sources, respectively.The intra-observer analysis showed significant systematic and random errors in the calibration factor at JPEG CR 10:1. The fixed inter-compression analysis demonstrated systematic errors in the calibration factor and recalculated vessel parameter results at CR 16:1 and for the random errors at CR 10:1 and 16:1. The variable inter-compression analysis presented systematic and random errors in the calibration factor and recalculated parameter results at CR 10:1 and 16:1. Any negative effect at CR 6:1 was found only for the calibration factor of the variable inter-compression analysis, which did not show up in the final vessel measurements.Compression ratios of 10:1 and 16:1 affected the QCA results negatively and therefore should not be used in clinical research studies.

Almost without any exemption, new cardiac catheterization laboratories are entirely digital without 35 mm cinefilm as the storage medium. In addition, existing laboratories are increasingly converting to the digital world. Aside from the organizational aspects, this has significant implications for the daily diagnostic review process of the procedures, and for the quantitative analysis of selected frames by QCA. The DICOM standard has now been well accepted in the catheterization laboratories. In stead of mechanical cine projectors, a department must decide on so-called DICOM-Viewers or 'digital Tagarno's'. In this paper the effects of DICOM on image quality and therefore on the visual interpretation of these images, as well as on QCA are discussed. Since the digital images can be enhanced, these look sharper than the conventional cinefilm images. However, edge enhancement has an effect on QCA, reason why the digital data must be stored in raw format. With the enormous amounts of digital data produced in a catheterization laboratory, image compression is of great importance. Currently, an international study is being carried out to determine which compression level is still acceptable from a visual interpretation and QCA point of view. Finally, the implications of the digital era on clinical trials are discussed. One of the important conclusions is that one should be encouraged not to switch from cinefilm to digital in the course of a trial, while a mixed population from the beginning is no problem, as long as the proper statistical calculations are carried out. In conclusion, despite the fact that there are still a number of items to be checked and possibly modified in the standard, the existing DICOM standard has succeeded in bringing widespread utilization of QCA in cardiac angiography closer than ever.

With the accepted use of (lossy) data compression at low compression factors (2, 3 and 4 on the Philips DCI), the question was posed whether higher lossy compression ratios can also be used without statistically affecting the results of quantitative coronary arteriography. In this study the influence of two data compression schemes (LOT and JPEG) at three different compression factors (5, 8 and 12) on coronary measurements was assessed with the Automated Coronary Analysis (ACA) package. A series of 30 original acquired digital images were compressed and decompressed at the different factors, and together with the original non-compressed images processed using the ACA package. In these images a total of 37 obstructed coronary segments were analyzed twice to assess the intra-observer variabilities in the obstruction and reference diameters and in the percent diameter stenosis. The results of the first and second measurements in each image were averaged, and from the differences in corresponding images with different compression ratios, the inter-compression variability was obtained. The results show that the intra-observer systematic errors in the absolute diameters are all small (0.07 mm), and statistically not significantly different. The intra-observer random errors for the compressed/decompressed series, however, were all larger (up to 0.21 mm) than for the original series (0.13 mm). Statistically significant differences in the intra-observer random errors were found for the JPEG compression scheme at a compression ratio of 5 and for the LOT scheme at a compression ratio of 12. The inter-compression systematic errors in the absolute diameter measurements were also small (0.07 mm) and not significant, while the random errors were found to be high in the range between 0.23 mm and 0.31 mm. Given the higher intra-observer variabilities for the compressed/decompressed image series as compared to original images, and the fact that all inter-compression variabilities were found to be so high, we must conclude that the higher compression ratios affect the results of QCA in a negative sense. In conclusion, the use of lossy data compression with JPEG or LOT compression schemes at ratios 5, 8 and 12 must be discouraged for QCA.

Background Anterior open treatment of the inguinal hernia with a tension-free mesh has reduced the incidence of hernia recurrence. The Lichtenstein procedure is the current reference technique for inguinal hernia treatment. Chronic pain has become the main postoperative complication after surgical inguinal hernia repair, especially following Lichtenstein. Preliminary experiences with a soft mesh positioned in the preperitoneal space (PPS) by transinguinal preperitoneal (TIPP) or total extraperitoneal (TEP) technique, showed promising results considering the reduction of postoperative chronic pain. Evolution of surgical innovations for inguinal hernia repair led to an open, direct approach with preperitoneal mesh position, such as TIPP. Based on the TIPP procedure, another preperitoneal repair has been recently developed, the transrectus sheath preperitoneal (TREPP) mesh repair. Methods The ENTREPPMENT trial is a multicentre randomized clinical trial. Patients will be randomly allocated to anterior inguinal hernia repair according to the TREPP mesh repair or TIPP procedure. All patients with a primary unilateral inguinal hernia, eligible for operation, will be invited to participate in the trial. The primary outcome measure will be the number of patients with postoperative chronic pain. Secondary outcome measures will be serious adverse events (SAEs), including recurrence, hemorrhage, return to daily activities (for example work), operative time and hospital stay. Alongside the trial health status, an economic evaluation will be performed. To demonstrate that inguinal hernia repair according to the TREPP technique reduces the percentage of patients with postoperative chronic pain from 12% to

Ischemic preconditioning studies employ one or more brief total coronary artery occlusions separated by complete reperfusion to limit infarct size during a subsequent prolonged coronary artery occlusion. We now present evidence that in anesthetized pigs a partial coronary artery occlusion without intervening reperfusion between the partial and prolonged total occlusions can also precondition the myocardium provided that the reduction in coronary blood flow is sufficiently severe. Thus infarct size was reduced after a 60 min total coronary artery occlusion when the total occlusion was preceded by a partial coronary occlusion that reduced coronary blood flow by 70% but not when the flow reduction was only 30%. In this two-stage coronary occlusion model the degree of protection appears greater in the epicardial than in the endocardial half. In view of evidence that brief occlusions of a coronary artery also protect myocardium outside its perfusion territory, we subsequently investigated whether ischemia in remote organs can protect myocardium. Because of reports that development of infarct size may be temperature dependent, we also investigated whether the cardioprotection by remote organ ischemia was temperature dependent. In anesthetized rats a 15 min coronary artery occlusion was more effective in reducing infarct size produced by a subsequent 60 min total coronary artery occlusion when the experiments were performed at a body core temperature of 30-31 degrees C than at 36-37 degrees C, while infarct size of animals which were subjected to only the 60 min total coronary artery occlusion was the same for the two body core temperatures. In rats with a body core temperature of 36-37 degrees C a 15 min mesenteric artery occlusion, but not a 15 min renal artery occlusion, reduced infarct size produced by a subsequent 60 min coronary artery occlusion. When the experiments were performed at 30-31 degrees C both the mesenteric and renal artery occlusions were protective. These observations indicate the local myocardial ischemia is not required to protect the myocardium during a prolonged coronary occlusion. We further investigated whether myocardium could also be protected by a cardiac stimulus which does not produce ischemia at all. For this purpose we electrically paced the left ventricle of anesthetized pigs to produce heart rates of 200 bpm (which did not lead to ischemia as assessed by a number of functional and biochemical variables) and found that 30 min of ventricular pacing reduced myocardial infarct size produced by a subsequent 60 min coronary artery occlusion. The protection by ventricular pacing involved activation of K+ATP channels as pretreatment with glibenclamide abolished the protection by ventricular pacing. We conclude that a number of distinctly different stimuli can protect the myocardium suggesting that ischemic myocardial preconditioning could be just one feature of a more general protection phenomenon.

Centralized, quantitative coronary analysis (QCA) has become the standard for determining change in coronary anatomy in clinical investigations. QCA systems and laboratory methods, however, vary among core facilities, and analysis variability among angiographic core laboratories (ACL) has not be studied. We evaluated QCA accuracy and variability among active ACL, using differing QCA systems by comparing analyses of phantom and clinical cinefilm images. Automated, unedited analyses were performed on images of 11 plexiglass phantom lumens (0.67-5.05 mm) acquired under varying radiographic conditions. Analysis differences from actual luminal diameters ranged widely (+0.42 - (-)0.45 mm) among ACL. Measurement of diameters1.0 mm were overestimated and diameters3.0 mm were underestimated. Measurements of midrange diameters (1.0 mm and3.0 mm) were most comparable among ACL (93% within +/- 0.2 mm). Clinical image analysis was performed using differing QCA systems and laboratory methodology on 11 randomly selected study films. Comparative analyses revealed significant variability between laboratories in the assessment of minimal lumen diameter (0.22 +/- 0.38 mm P0.05). These data describe analysis variability among ACL and demonstrate a need for establishing ACL performance standards.

In the transition period between 35-mm cinefilm as the medium for coronary arteriographic data and digital media such as CD-R, S-VHS videotape has been used both as an exchange and store medium, and for quantitative coronary arteriographic (QCA) studies. To determine the extent to which S-VHS video tape affects QCA measurements, an X-ray phantom study was completed. A plexiglass phantom with 12 straight circular tubes (0.51-5.00 mm in diameter) filled with contrast medium was recorded under clinical conditions using both the 5" and 7" modes of the image intensifier with the phantom tubes positioned horizontally as well as vertically in the field of view. The digitally acquired images were recorded on S-VHS tape without any image enhancement (raw data) and with default image enhancement. Video frames were then selected on a professional VCR such that individual tubes were positioned in the center of the field of view and digitized (512(2) x 8 bits) with a high-quality frame grabber onto a QCA workstation. The contours along the individual tubes were defined using previously validated automated contour detection techniques. For each tube, an average diameter (mm) and a standard deviation (mm) were calculated. Calibration was based on a cm-grid acquired at the same geometry as the phantom. Due to the poor signal-to-noise ratio and the limited bandwidth of the S-VHS video tape, the following objective observations were made: 1) large overestimations (up to 0.87 mm) occur for tube sizes below 1 mm for vertically positioned tubes; 2) random errors in measurements are much larger for vertically positioned tubes (0.36 mm, 7" II) than for horizontally positioned tubes (0.17 mm, 7" II); and 3) little differences in results between enhanced and nonenhanced images were found due to these deteriorating factors. In conclusion, S-VHS video tape is unacceptable for QCA and should be excluded from quantitative angiographic clinical trials.

The ability of myocardium to adapt to ischemic stress has already been documented in both experimental and clinical studies employing intermittent ischemia some 15 years ago. For instance, it was shown that changes in metabolic markers of myocardial ischemia were much less during the second of two consecutive, but identical coronary blood flow reductions in pigs.1 Similarly, the second of two consecutive but identical atrial pacing stress tests in patients undergoing a cardiac catheterization for suspected coronary artery disease showed less severe signs of ischemia.2 At that time, no attempt was made to elucidate the mechanism of the altered response during the second episode of ischemia as the purpose of these studies was to develop models of repeated reversible ischemia with reproducible changes in the various markers of ischemia. In such models it would then be possible to evaluate the effects of pharmacological interventions with the animal or patient serving as its own control. Several subsequent studies on the metabolic and functional consequences of multiple brief periods of ischemia also revealed the absence of cumulative losses in tissue levels of high energy phosphates and in regional contractile function, but these have not always been consistent findings.3

As part of a study on the relationship of tumour phenotype and behaviour, we have characterized two head and neck squamous cell carcinoma cell lines, derived from human laryngeal carcinomas and designated HLaC'79 and HLaC'82. Cytogenetic analysis revealed that HLaC'79 and HLaC'82 shared 10 major chromosome rearrangements indicating that the cell lines had a common origin. In the extremely complex chromosomal patterns, abnormalities were found in chromosomes 1, 3 (surplus 3q) and 5 (i(5p) x 2). Both cell lines displayed constitutive expression of vimentin and were capable of anchorage-independent growth in agarose gels. However, in spite of their common origin specific differences were found. Cells of HLaC'79 were spindle shaped and formed tumours in athymic mice. In contrast, cells of HLaC'82 had a compact morphology, contained less vimentin, were more contact inhibited and were not tumorigenic. These results indicate that malignant transformation in HLaC'82 was partially reversed.

To quantify regional conversion of angiotensin (ANG) I to ANG II and its degradation to peptides other than ANG II, monoiodinated 125I-labeled ANG I was given to anesthetized pigs by constant infusion into the left cardiac ventricle. At steady state, blood samples were taken from the aorta and various regional veins. Distribution volume of ANG I appeared to be 24% of body weight. After angiotensin-converting enzyme (ACE) inhibitor treatment, fractional ANG I metabolism (fraction of arterially delivered ANG I that was metabolized during a single passage of blood) was 10% in the lungs (conversion 4%), compared with 56% in the combined systemic vascular beds (conversion 1%). Fractional ANG I metabolism during ACE inhibition was 93% in the kidney; 50-70% in myocardium, skeletal muscle, head, and skin; 21% in the left cardiac cavity; and 14% in the right cardiac cavity. Without ACE inhibition, fractional ANG I metabolism was 29% in the lungs (conversion 25%); 49% in the combined systemic vascular beds (conversion 10%); 38% in the left cardiac cavity (conversion 11%); and 14% in the right cardiac cavity (conversion 0%). It may thus be concluded that 1) extrapulmonary vascular beds make an important contribution to the conversion of circulating ANG I and 2) there is rapid extrapulmonary ANG I degradation that does not depend on ANG I-II conversion.