Tripled yield in direct-drive laser fusion through statistical modelling.

Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium-tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules-several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics.

Magnetic engineering of stable rod-shaped stem cell aggregates: circumventing the pitfall of self-bending.

A current challenge for tissue engineering while restoring the function of diseased or damaged tissue is to customize the tissue according to the target area. Scaffold-free approaches usually yield spheroid shapes with the risk of necrosis at the center due to poor nutrient and oxygen diffusion. Here, we used magnetic forces developed at the cellular scale by miniaturized magnets to create rod-shaped aggregates of stem cells that subsequently matured into a tissue-like structure. However, during the maturation process, the tissue-rods spontaneously bent and coiled into sphere-like structures, triggered by the increasing cell-cell adhesion within the initially non-homogeneous tissue. Optimisation of the intra-tissular magnetic forces successfully hindered the transition, in order to produce stable rod-shaped stem cells aggregates.

Use of magnetic forces to promote stem cell aggregation during differentiation, and cartilage tissue modeling.

Magnetic forces induce cell condensation necessary for stem cell differentiation into cartilage and elicit the formation of a tissue-like structure: Magnetically driven fusion of aggregates assembled by micromagnets results in the formation of a continuous tissue layer containing abundant cartilage matrix.

Examination of periodontal pathogens in stenotic valve specimens and in whole blood samples in patients affected by aortic valve stenosis and chronic periodontitis.

Periodontitis may be a risk factor for atherosclerosis and coronary heart disease. The influence of periodontal pathogens in cardiovascular diseases needs further investigation. Therefore, the aims of this clinical study are: to test the presence of periodontal bacteria DNA in aortic valves and to assess the concomitant presence of the same periodontal bacteria DNA in whole blood samples in patients affected by aortic valve stenosis and chronic periodontitis. Nineteen consecutive patients (12 males and 7 females, age: 49-85 years) were enrolled in this study after having been subjected to a complete periodontal evaluation to confirm the diagnosis of chronic periodontitis. All patients were scheduled for aortic valve replacement surgery. After clinical and microbial periodontal examination, the aortic valve tissue specimens were obtained by excision during valve replacement surgery and the patients were subjected to the whole blood sampling before the surgery. The polymerase chain reaction technology was used to detect the putative periodontal pathogens Tannerella forshytia, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Fusobacterium nucleatum, Campylobacter rectus, Eikenella corrodens and Treponema denticola. Neither the 19 aortic valve specimens nor the blood samples were positive for the genoma of the selected periodontal pathogens. The selected periodontal pathogens did not colonize the aortic valve of patients affected by stenosis and bacterial genoma was not present in whole blood samples. A high blood pressure at the aortic valve may prevent the adhesion and proliferation of bacterial colonies.

An endothelin-converting enzyme homologue in the locust, Locusta migratoria: functional activity, molecular cloning and tissue distribution.

Endothelin-converting enzyme is the key enzyme in the process of endothelin production. Endothelin is a peptide that plays an important role in vasoconstriction and the development of neural crest-derived cells in vertebrates. Activity assays performed on membrane extracts from Locusta migratoria brain revealed the existence of a protease activity responsible for the formation of mature endothelin-1 from its precursor, big endothelin. Cloning experiments led to a cDNA sequence (Lom ECE) with an open reading frame of 727 amino acid residues displaying all the characteristic ECE features. A comparison of ECE activity levels among different tissues of the locust showed a high enzyme activity in the gonads and midgut. RT-PCR experiments showed a wide tissue distribution of Lom ECE mRNA, with transcription being most abundant in brain tissue.

Simultaneous surgical treatment of chronic post-traumatic aneurysm of the thoracic aorta, diaphragmatic hernia and giant emphysema bulla.

Thoraco-abdominal blunt trauma can lead to multiple injuries of several organs. We report a case of a patient in whom, 10 years after a trauma, a chest X-ray showed visceral herniation into the left thorax. Angio computed tomographic scan (CTS) and magnetic resonance imaging (MRI) confirmed these lesions and also showed a saccular thoracic aortic aneurysm. During the surgical procedure a giant post-traumatic emphysema bulla of the left lower pulmonary lobe was discovered and repaired. In the presence of diaphragmatic injuries, CTS and MRI are mandatory for excluding other organ involvement, and during the surgical procedure, careful inspection of left thorax and abdomen should always be done to repair other possible injuries not seen before.

Relation of the -174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization.

Interleukin (IL)-6 plasma levels are predictive of major cardiovascular events. The -174 G/C promoter polymorphism of the IL-6 gene affects basal levels in vivo and transcription rates in vitro, but its association with IL-6 acute phase levels among patients with coronary artery disease has not been investigated. In 111 patients with multivessel coronary artery disease undergoing elective coronary artery bypass graft surgery, we prospectively assessed genotype at position -174 and serial blood levels of IL-6 and other inflammatory indexes. Clinical and surgical characteristics did not differ among genotypic groups. IL-6 levels--measured daily up to 72 hours before surgery, after surgery, and at discharge--showed a mean 17-fold increase, peaking at 24 hours (p <0.0001). IL-6 levels (but not fibrinogen, white-blood cell count, and C-reactive protein values) differed significantly according to the -174 genotype (p = 0.042 for difference between areas under the curve), the 62 GG homozygotes exhibiting higher concentrations than the 49 carriers of the C allele (widest difference at 48 hours, p = 0.015 in multivariate analysis). GG homozygosity was associated with longer stays in the intensive care unit (2.5 +/- 3.4 vs 1.4 +/- 0.9 days, p = 0.02) and in the hospital (6.7 +/- 4.0 vs 5.3 +/- 1.4 days, p = 0.02) than C carriership. Rates of postoperative death, myocardial infarction, and stroke were 8% in GG homozygotes and 2% in C-carriers (p = 0.16). The IL-6-174 GG genotype is associated with higher acute phase levels of IL-6 and with longer stays in the hospital and in the intensive care unit than C allele carriership after surgical coronary revascularization.

Clinical and angiographic effects of chronic calcium channel blocker therapy continued beyond first postoperative year in patients with radial artery grafts: results of a prospective randomized investigation.

BACKGROUND: This study was conceived to elucidate the clinical and angiographic effects of chronic calcium channel blocker therapy (CCCBT) continued after the first postoperative year in patients in whom the radial artery (RA) was used for myocardial revascularization. METHODS AND RESULTS: Patients who received RA grafts at our institution and who at 1 year had no scintigraphic evidence of ischemia in the RA territory or angiographic evidence of RA malfunction (n=120) were randomly assigned to continue (n=63) or suspend (n=57) the CCCBT with diltiazem (120 mg/d). After 5 years, all patients were reassessed clinically and by stress myocardial scintigraphy, and 87 of them (45 from the continued group that continued CCCBT and 42 from the group that suspended CCCBT) were restudied angiographically. No differences regarding either the clinical and scintigraphic results or the RA angiographic status were demonstrated between the 2 groups. CONCLUSIONS: After the first postoperative year, the continuation of CCCBT does not affect RA graft patency or clinical and scintigraphic results.

Mediastinitis following graft replacement of the ascending aorta: conservative approach by omental transposition.

A 57-year-old patient underwent prosthetic replacement of a previously implanted ascending aorta graft and developed a periprosthetic purulent collection 1 month later. He was successfully treated by debridement of infected tissues, antiseptic irrigation and transposition of an omental flap. The postoperative course was uneventful. A chest computed tomography scan performed 15 months later showed no signs of perigraft infection. Prompt conservative surgical treatment including omental transposition can be effective in the treatment of mediastinitis following graft replacement of the ascending aorta.

An unusual source of massive intra-abdominal hemorrhage during cardio-pulmonary bypass.

Intra-abdominal hemorrhage occurring while on cardio-pulmonary bypass (CPB) is a rare and potentially lethal event during coronary artery bypass procedures. We herein report an unusual case in which massive intra-abdominal bleeding during CPB originated from a previously undiagnosed ovarian tumor, leading to acute anemization and hemodynamic instability and requiring emergency gynecologic surgery.

Highly sensitive and selective fluorescence assays for rapid screening of endothelin-converting enzyme inhibitors.

The highly potent vasoconstrictor peptide endothelin (ET) is generated from an inactive precursor, big endothelin (bET), by endothelin-converting enzyme (ECE). ECE is a phosphoramidon-sensitive zinc metallopeptidase, which is closely related to neprilysin (neutral endopeptidase). It is possible that compounds which inhibit the formation of ET may be used as new drugs for the treatment of cardiovascular diseases. Such an approach requires a fast, simple and selective assay to measure ECE activity, allowing rapid screening of inhibitors. We describe here two new ECE substrates based on the concept of 'intramolecularly quenched fluorescence' which may fulfill this aim. One, S(1) [Pya(21)-Nop(22)-bET-1(19--35)], is the (19--35) fragment of the natural peptide big-ET-1(1--38), which is modified by introducing the fluorescent amino acid, pyrenylalanine (Pya), in position 21 and a quencher, p-nitrophenylalanine (Nop), in position 22. The second substrate (S(2)) is a small peptide, Ac-Ser-Gly-Pya-Lys-Ala-Phe-Ala-Nop-Gly-Lys-NH(2), from a biased substrate peptide library. The recombinant, hECE-1c, cleaved both Pya(21)-Nop(22)-bET-1(19--35) and the natural substrate selectively between residues 21 and 22, whereas cleavage occurred between alanine and phenylalanine in the small peptide. In both cases, this generated intense fluorescence emission. The synthesis and kinetic parameters of these substrates are described. These assays, which can be used directly on tissue homogenates, are the most sensitive and selective described to date for ECE, and are easily automated for a high-throughput screening of inhibitors.

Should severe monolateral asymptomatic carotid artery stenosis be treated at the time of coronary artery bypass operation?

OBJECTIVE: The optimal treatment of severe monolateral asymptomatic carotid artery stenosis (SMACS) in patients undergoing coronary artery bypass grafting (CABG) is still controversial. MATERIALS AND METHODS: This study is based on the in-hospital and mid-term (>5 years) clinical results of a cohort of 139 consecutive CABG patients with SMACS operated at our Institution between January 1989 and December 1995. In the first 73 patients (no carotid surgery group), the SMACS was left untouched at the time of coronary surgery, whereas in the remaining 66 (carotid endoarterectomy group), the carotid stenosis was treated either immediately before or concomitantly with the CABG procedure (depending on the severity of the anginal symptoms). RESULTS: The overall preoperative characteristics of the patients were comparable. The in-hospital results were similar between the two groups with regard to mortality, stroke and major postoperative complications. However, at mid-term follow-up, significantly more patients of the no carotid surgery group suffered cerebral events (transient or permanent) ipsilateral to the SMACS or the lesion had to be operated on. CONCLUSIONS: The concomitant treatment (either staged or simultaneous) of SMACS at the time of CABG does not influence the in-hospital results, but confers significant neurological protection during the years after the operation.

Coronary angiodysplasia of epicardial and intramural vessels.

A case of coronary angiodysplasia combining large aneurysms of epicardial arteries with diffuse malformation of intramural vessels is reported. Clinical presentation may mimic a vascularized cardiac tumor. Although leaking of the aneurysms in the pericardial space may occur, this entity seems to have a benign prognosis not requiring surgical repair.

The unclampable ascending aorta in coronary artery bypass patients: A surgical challenge of increasing frequency.

BACKGROUND: The unclampable ascending aorta (UAA) is a condition increasingly encountered during CABG procedures. We report our experience with CABG patients with UAA and place particular emphasis on the preoperative diagnosis and surgical management. METHODS AND RESULTS: UAA was diagnosed in 211 of 4812 consecutive CABG patients (4.3%). On the basis of the chest radiograph, echocardiogram, and coronary angiograph, a preoperative diagnosis was achieved in only 58 patients (27.4%). An age of >70 years, diabetes, smoking, unstable angina, diffuse coronaropathy, and peripheral vasculopathy were all predictors of UAA. Patients were treated with hypothermic ventricular fibrillation (no-touch technique n=129) or beating heart revascularization (no-pump technique n=82) depending on the possibility of founding an arterial cannulation site. The overall in-hospital mortality rate was 2.8% (6 of 211) with no differences between the 2 surgical strategies. The no-touch technique was associated with a greater incidence of neurological complications (stroke and transient ischemic attack), renal insufficiency, and stay in the intensive care unit and hospital. However, at midterm follow-up, more patients of the no-pump group had ischemia recurrence. CONCLUSIONS: A preoperative diagnosis of UAA is achievable only in a minority of patients, which highlights the necessity revising the current diagnostic protocols. The use of the no-touch technique is associated with an high perioperative risk but a superior possibility of complete revascularization, whereas adoption of the no-pump strategy ensures a smoother postoperative course at the expense of an higher incidence of ischemia recurrence.

Binding properties of a highly potent and selective iodinated aminopeptidase N inhibitor appropriate for radioautography.

Aminopeptidase N (APN) is a zinc metallopeptidase involved in the inactivation of biologically active peptides. The knowledge of its precise distribution is crucial to investigate its physiological role. This requires the use of appropriate probes such as the recently developed highly potent and selective radiolabeled APN inhibitor 2(S)-benzyl-3-[hydroxy(1'(R)-aminoethyl)phosphinyl]propanoyl-L-3-[ (12 5)I]iodotyrosine ([(125)I]RB 129). Its binding properties were investigated using rat brain homogenates (K(d)=3.4 nM) or APN expressed in COS-7 cells (K(d)=0.9 nM). The specific binding was 95% at [K(d)], and preliminary autoradiography in intestine is promising. The decreased affinity of [(125)I]RB 129 (=10(-6) M) for the E(350)D APN mutant, supports the critical role of E(350) in the amino-exopeptidase action of APN.

Combined Surgery for cardiac and carotid disease: management and results of a rational approach.

OBJECTIVES: The aim of the present study was to apply a rational plan for simultaneous cardiac and carotid surgery in high-risk patients. MATERIALS AND METHODS: A consecutive series of 89 patients with coexisting severe cardiac and carotid disease were operated on during a 5-year period with routinary carotid shunting, moderate hypothermia and balanced anaesthesia. The combined surgical procedures were coronary artery by-pass grafts (CABG) + carotid endarterectomy (CEA) in 81 patients, CABG + CEA + aortic valve replacement (AVR) in four patients, and four cases of CEA + AVR. RESSULTS: Two deaths (2%), three acute myocardial infarctions (3%) and one (1%) major stroke occurred in five patients during the perioperative (30 days) period for a combined rate of death and/or disabling stroke of 3%. There were five reversible neurological deficits. Carotid and aortic mean clamping times were 9 and 60 min respectively. Patients were discharged after a mean length of stay in Intensive Care Unit (ICU) of 131 h and 7 days of hospitalisation post-ICU. CONCLUSIONS: Based on our results, combined interventions of CEA and CABG can be performed with an acceptable morbidity and mortality when severe carotid stenosis is associated with advanced, symptomatic cardiac disease. The management of these patients needs careful and appropriate pre-intra and post-operative assessment and timing aimed to reduce the ischaemic injuries, both cardiac and cerebral, especially during CBP time.

Elevated levels of C-reactive protein before coronary artery bypass grafting predict recurrence of ischemic events.

C-reactive protein was measured in 86 patients undergoing coronary artery bypass graft surgery. Patients were followed up for 3.2 years (range 1 to 6). Patients with C-reactive protein > or = 3 mg/L had significantly increased risk of recurrent ischemia at 1 to 6 years after intervention.

Perioperative management of a patient with Werlhof disease undergoing myocardial revascularization.

We herein report the case of a patient with idiopathic thrombocytopenic purpura (Werlhof disease) and coronary artery disease undergoing myocardial revascularization. The use of monomeric immunoglobulins, corticosteroids, platelets transfusion, use of a cell saver, normothermic cardiopulmonary bypass, aprotinine and homologous blood transfusion were combined in order to minimize the risk of bleeding complications in the postoperative period.

Individualized surgical strategy for the reduction of stroke risk in patients undergoing coronary artery bypass grafting.

BACKGROUND: This study was designed to evaluate the efficacy of a protocol of systematic screening of the ascending aorta and internal carotid arteries and individualization of the surgical strategy to the ascending aorta and internal carotid arteries status in reducing the stroke incidence among patients undergoing coronary artery bypass grafting. METHODS: On the basis of a pre- and intraoperative screening of the ascending aorta and internal carotid arteries, 2,326 consecutive patients undergoing coronary artery bypass grafting were divided in low, moderate, and high neurologic risk groups. In the high-risk group dedicated surgical techniques were always adopted and the reduction of the neurologic risk was considered more important than the achievement of total revascularization. RESULTS: The incidence of perioperative stroke in the high-risk group was similar to those of the other two groups (1.1 versus 1.3 and 1.1%, respectively; p = not significant); however, angina recurrence was significantly more frequent in the high-risk group. CONCLUSIONS: The described strategy allows a low rate of perioperative stroke in high-risk patients undergoing coronary artery bypass grafting. Whether the reduction of the neurologic risk outweighs the benefits of complete revascularization remains to be determined.

Midterm clinical and angiographic results of radial artery grafts used for myocardial revascularization.

OBJECTIVE: To evaluate the midterm angiographic results of the use of radial artery grafts for myocardial revascularization. METHODS: The first 68 consecutive surviving patients who received a radial artery graft proximally anastomosed to the aorta at our institution were studied again at 5 years (mean 59 +/- 6.5 months) of follow-up; 48 of these patients had previously undergone an early angiographic examination. The response of the radial artery to the endovascular infusion of serotonin was evaluated 1 and 5 years after the operation, and the midterm status of the radial artery graft was correlated with the degree of preoperative stenosis of the target vessel and with calcium-channel blocker therapy. RESULTS: The patency and perfect patency rates of the radial artery grafts 5 years after the operation were 91.9% and 87.0%, respectively. All radial artery grafts that were patent early after the operation remained patent at midterm follow-up, and early parietal irregularities in 7 patients were seen to have disappeared after 5 years. The early propensity toward graft spasm after serotonin challenge was markedly decreased at midterm follow-up. The continued use of calcium-channel antagonists after the first postoperative year did not influence the radial artery graft status, whereas the preoperative severity of the target-vessel stenosis markedly influenced the angiographic results. CONCLUSIONS: The midterm angiographic results of radial artery grafts used for myocardial revascularization are excellent. The correct surgical indication is essential. Continued therapy with calcium-channel antagonists after the first year does not influence the midterm angiographic results.