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.

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.

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.

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.

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.

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.

Stimulation of translation by reactive oxygen species in a cell-free system.

Wheat germ lysate was used as a model system for in vitro translation. We show that an increase of the exchange surface between the reaction mixture and the atmosphere enhanced the amount of incorporated cysteine, indicating that early arrest of protein synthesis previously observed in such a system was due to oxygen starvation in the reaction mixture. This hypothesis was confirmed since the amount of proteins synthesized and the rate of translation increased when oxygen was added. We show that an addition of hydrogen peroxide to the translation mixture had the same effect as oxygen, allowing us to postulate that stimulation could be due to a common property between both molecules: the oxidizing behaviour. Free radicals in in vitro translation were believed to be involved since the utilization of iron chelating agents inhibited translation. This hypothesis was emphasized by the positive effect of a free radical generating system and the negative effect of free radical scavengers. These experiments suggest that the superoxide radical plays an important role in in vitro translation.

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.

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.

Systematic clinical and angiographic follow-up of patients undergoing minimally invasive coronary artery bypass.

OBJECTIVE: We herein analyze the results of the systematic clinical and angiographic control performed in a series of 77 consecutive patients undergoing minimally invasive coronary artery bypass. METHODS AND RESULTS: From January 1995 to June 1997, 77 patients underwent minimally invasive coronary artery bypass at our institution. There was one inhospital death, one noncardiac late death, and five patients had to be reoperated for graft malfunction. A total of 76 patients underwent postoperative angiographic follow-up. In 66 cases (86.8%) the thoracic artery graft, the target vessel, and the anastomosis were patent and functioning normally. In one case the graft was occluded. In the remaining nine cases the thoracic artery graft was patent but with major anomalies of either the anastomosis, the target vessel, or the course of the thoracic artery. Patients operated using especially designed instruments had angiographic results clearly superior to those of patients operated using conventional instrumentation (perfect patency rate 100% vs 81.8%). At a mean follow-up of 18 months, 98.5% of the surviving patients are asymptomatic with negative myocardial scintigraphy. CONCLUSIONS: The perfect patency rate of minimally invasive revascularization performed without the use of dedicated instruments is unacceptably low. The use of specific devices is likely to result in a substantial improvement in the angiographic results.

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.

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.

The internal mammary artery malperfusion syndrome: late angiographic verification.

BACKGROUND: Here we report our experience with the incidence and the surgical treatment of the internal mammary artery (IMA) malperfusion syndrome, evaluate the predictive role of previously described risk factors for the syndrome, and assess the late patency of IMA grafts in patients in whom an IMA malperfusion syndrome was diagnosed and treated by additional saphenous vein grafting of the left anterior descending coronary artery. METHODS: From June 1992 to November 1995, 969 IMAs were anastomosed to the left anterior descending coronary artery system. In 11 patients, IMA malperfusion syndrome was diagnosed and treated by additional saphenous vein grafting of the LAD. There were 8 men and 3 women with a mean age of 58.9 years. The angiographic and clinical data for each patient were reviewed, and all but 1 surviving patient underwent late angiographic control (mean follow-up, 18 months; range, 4 to 46 months). RESULTS: One patient died in the hospital. No previously described risk factor was strongly associated with the occurrence of IMA malperfusion syndrome. Late angiography revealed a malfunctioning IMA graft in 7 of the 9 patients. A string sign was observed in 1 patient and a normally functioning IMA anastomosed to a diagonal branch not connected to the LAD, in another. In no patient was a widely patent and normally functioning IMA graft observed. CONCLUSIONS: In our series, a high proportion of IMA grafts were found to be malfunctioning at late angiography. This observation, in contrast to previous reports, suggests that IMA malperfusion syndrome can often be attributable to technical problems in harvesting the IMA or in performing the IMA anastomosis. Functional IMA insufficiency seems to play only a marginal role in determining the IMA malperfusion syndrome.

Composite arterial conduits for a wider arterial myocardial revascularization.

From October 1991 to May 1993, 130 patients were submitted to myocardial revascularization using complex preformed arterial conduits. The age ranged from 29 to 75 years (mean age, 60.1 years); 121 patients were male. One hundred twenty-six patients had double- or triple-vessel disease. The mean ejection fraction was 0.53 (range, 0.22 to 0.79); only 6 patients had an ejection fraction less than 0.35. In 6 cases the procedure was a reoperation. We used 360 arterial conduits, 163 of which as free grafts (3 left internal mammary arteries, 16 right internal mammary arteries, 86 inferior epigastric arteries, 57 radial arteries, and 1 right gastroepiploic artery). One hundred fifty-four free grafts were anastomosed to one or both internal mammary arteries and one to a radial artery. We constructed 136 complex arterial conduits (branched, lengthened, or both). In 6 cases a double arterial system had to be used in a single patient. There was no operative mortality, and no inotropic or mechanical supports were used. The overall mortality rate was 1.5%. Early angiographic controls (between the 7th and 15th postoperative days) demonstrated 100% patency; late angiographic controls (at a mean interval of 9.5 months after operation) documented a mean patency rate ranging from 94.1% of the radial arteries to 100% of the left internal mammary arteries and right gastroepiploic arteries. At a mean follow-up of 7.2 months (range, 1 to 15 months) all patients are alive without recurrence of symptoms.

Lesions of the target vessel during minimally invasive myocardial revascularization.

BACKGROUND: Minimally invasive coronary artery bypass grafting has recently been introduced into cardiac surgery. In this report we discuss the incidence of surgically induced distal target vessel stenosis in patients who undergo the minimally invasive coronary artery bypass grafting procedure, which represents a major drawback of the procedure in our experience. METHODS: Doppler evaluation of mammary artery flow was performed postoperatively in all 55 patients who underwent minimally invasive coronary artery bypass grafting at our institution. Angiography was performed in the first 35 consecutive patients for control purposes and in 2 patients who complained of angina recurrence. RESULTS: In 32 of the first 35 consecutive patients, the anastomosis was found to be functioning normally and the distal left anterior descending artery was normal; in the remaining 3 patients we found mammary artery occlusion, anastomotic stenosis, and stenosis of the anastomosis and the distal left anterior descending artery in 1 patient each. A distal left anterior descending artery stenosis was found in the only 2 patients who underwent late angiography. CONCLUSIONS: Surgically induced distal target vessel stenosis represents a major drawback of minimally invasive coronary artery bypass grafting in our experience. Further improvement in the means of achieving coronary artery occlusion, as well as in anticoagulant and antiplatelet therapy, is mandatory before minimally invasive coronary artery bypass grafting can be confidently accepted into clinical practice.

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.

Early results with the minimally invasive thoracotomy for myocardial revascularization.

OBJECTIVE: We report the early results of the left anterior descending artery revascularization through a minimally invasive thoracotomy, examining the main technical aspects of the operation. METHODS: From January 1995 to September 1996, 51 patients underwent myocardial revascularization through a mini-thoracotomy on beating heart without cardiopulmonary bypass. The main indication to operation was limited lesions of the left anterior descending artery with contra-indications or high risk of failure of angioplasty. The position of the patient was the same than traditional surgery; the chest was opened on the fourth left intercostal space; the left internal mammary artery harvested under direct vision; temporary occlusion of the left anterior descending was obtained prevalently using 5-0 poliypropilene sutures; the anastomosis was performed with single or double 7-0 or 8-0 suture. In six patients the chest was closed and a conventional open-heart operation was performed due to internal mammary artery or left anterior descending unsuitability for minimally invasive revascularization. All the patients were submitted after operation to early angiographic control and/or a Doppler study of the mammary flow. RESULTS: There was no intra-operative mortality. One patient had a postoperative myocardial infarction of the anterior-lateral wall of the left ventricle, and died after an emergency open-heart operation. In one case the patient was reopened after a few hours for a bleeding. Three patients showed various degrees of anastomotic stenosis at the angiographic control. CONCLUSIONS: Several technical difficulties can play an important role in the operative outcome because a single repeated technical error could not fully explain these heterogeneous observed failures. The technique of myocardial revascularization through a left anterior small thoracotomy might present several critical points, particularly: (1) the harvesting of LIMA, meaning the preservation of integrity of the arterial wall and adequacy of the length; (2) the method of the temporary closure of the LAD during of the anastomosis; (3) the stabilization of the LAD and the surgical technique of the anastomosis; (4) the methods for intraoperative control of the patency of the anastomosis. All points mentioned have been thought in our experience to be causes of early failure.

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.

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.

Valve replacement with the tilting disc Sorin prosthesis in patients with narrow aortic annulus.

The Authors summarize their 5-year experience of the clinical use of the Sorin tilting disc prosthesis in 40 patients (group A) with narrow aortic annulus, compared with a control group (group B: 116 patients) where a larger Sorin prosthesis was implanted. Follow-up lasted from 1 to 60 months, with a mean of 25.6 +/- 12.3 in group A and 20.4 +/- 11.9 in group B. Early and late mortality were low: 1/40 and 2/39 (2.5 and 5.1%) in group A and 4/116 and 9/112 (3.4 and 8.0%) in group B (p = NS): only two deaths, one in each group, were prosthesis-related. Actuarial survival was comparable: 91.2% (CL: 96.3-86.1%) in group A and 78.0% (CL: 87.6-68.4%) in group B, as were probability of being event-free and alive, non-reoperated and with few or no symptoms [group A: 61.7% (CL: 72.4-51.0%) and 77.4% (CL: 85.9-68.9%) respectively; group B: 78.8% (CL: 83.4-74.2%) and 61.1% (CL: 85.9-68.9%) respectively]. The Authors conclude that the Sorin tilting disc prosthesis is a reliable valve substitute in the narrow aortic annulus; they recommend that enlargement procedures should be confined only to patients with annulus size less than 19 mm.