Demonstration of high-energy 2 omega (526.5 nm) operation on the National Ignition Facility Laser System.

A single beamline of the National Ignition Facility (NIF) has been operated at a wavelength of 526.5 nm (2 omega) by frequency converting the fundamental 1053 nm (1 omega) wavelength with an 18.2 mm thick type-I potassium dihydrogen phosphate (KDP) second-harmonic generator (SHG) crystal. Second-harmonic energies of up to 17.9 kJ were measured at the final optics focal plane with a conversion efficiency of 82%. For a similarly configured 192-beam NIF, this scales to a total 2 omega energy of 3.4 MJ full NIF equivalent (FNE).

National Ignition Facility laser performance status.

The National Ignition Facility (NIF) is the world's largest laser system. It contains a 192 beam neodymium glass laser that is designed to deliver 1.8 MJ at 500 TW at 351 nm in order to achieve energy gain (ignition) in a deuterium-tritium nuclear fusion target. To meet this goal, laser design criteria include the ability to generate pulses of up to 1.8 MJ total energy, with peak power of 500 TW and temporal pulse shapes spanning 2 orders of magnitude at the third harmonic (351 nm or 3omega) of the laser wavelength. The focal-spot fluence distribution of these pulses is carefully controlled, through a combination of special optics in the 1omega (1053 nm) portion of the laser (continuous phase plates), smoothing by spectral dispersion, and the overlapping of multiple beams with orthogonal polarization (polarization smoothing). We report performance qualification tests of the first eight beams of the NIF laser. Measurements are reported at both 1omega and 3omega, both with and without focal-spot conditioning. When scaled to full 192 beam operation, these results demonstrate, to the best of our knowledge for the first time, that the NIF will meet its laser performance design criteria, and that the NIF can simultaneously meet the temporal pulse shaping, focal-spot conditioning, and peak power requirements for two candidate indirect drive ignition designs.

Effects of subchronic inhalation exposure of rats to emissions from a diesel engine burning soybean oil-derived biodiesel fuel.

There is increasing interest in diesel fuels derived from plant oils or animal fats ("biodiesel"), but little information on the toxicity of biodiesel emissions other than bacterial mutagenicity. F344 rats were exposed by inhalation 6 h/day, 5 days/wk for 13 wk to 1 of 3 dilutions of emissions from a diesel engine burning 100% soybean oil-derived fuel, or to clean air as controls. Whole emissions were diluted to nominal NO(x) concentrations of 5, 25, or 50 ppm, corresponding to approximately 0.04, 0.2, and 0.5 mg particles/m(3), respectively. Biologically significant, exposure-related effects were limited to the lung, were greater in females than in males, and were observed primarily at the highest exposure level. There was a dose-related increase in the numbers of alveolar macrophages and the numbers of particles in the macrophages, as expected from repeated exposure, but no neutrophil response even at the highest exposure level. The macrophage response was reduced 28 days after cessation of the exposure. Among the high-level females, the group mean lung weight/body weight ratio was increased, and minimal, multifocal bronchiolar metaplasia of alveolar ducts was observed in 4 of 30 rats. Lung weights were not significantly increased, and metaplasia of the alveolar ducts was not observed in males. An increase in particle-laden macrophages was the only exposure-related finding in lungs at the intermediate and low levels, with fewer macrophages and fewer particles per macrophage at the low level. Alveolar histiocytosis was observed in a few rats in both exposed and control groups. There were statistically significant, but minor and not consistently exposure-related, differences in body weight, nonpulmonary organ weights, serum chemistry, and glial fibrillary acidic protein in the brain. There were no significant exposure-related effects on survival, clinical signs, feed consumption, ocular toxicity, hematology, neurohistology, micronuclei in bone marrow, sister chromatid exchanges in peripheral blood lymphocytes, fertility, reproductive toxicity, or teratology. This study demonstrated modest adverse effects at the highest exposure level, and none other than the expected physiological macrophage response to repeated particle exposure at the intermediate level.

Update in cardiac surgery.

Cardiac surgery continues to evolve in response to advances in technology, patient demands, and healthcare reimbursement. The development of minimally invasive operative techniques and laser technology has enhanced the therapeutic armamentarium available to the cardiac surgeon. Advances in biomaterial development will see the artificial heart in clinical trials by the millennium.

New developments in employee assistance programs.

Employee assistance programs have developed from alcoholism assessment and referral centers to specialized behavioral health programs. Comprehensive employee assistance programs are defined by six major components: identification of problems based on job performance, consultation with supervisors, constructive confrontation, evaluation and referral, liaison with treatment providers, and substance abuse expertise. Other services have been added as enhancements to the basic model and include managed behavioral health activities and professional assistance committees, which provide services for impaired professionals and executives. Recent developments in the field are illustrated through examples from the experience of the employee assistance program at the University of Maryland Medical System in Baltimore.

Four years experience of a hospital's impaired physician committee.

Physician impairment contributes to patient morbidity, malpractice claims, physician license loss and suicide. This paper describes four years of experience of the University of Maryland's Professional Assistance Committee. The committee is composed of medical staff members. Its mission is to help impaired physicians obtain assessment, treatment and monitoring, and to protect patients from harm. The committee has evaluated 23 cases over the past four years. Ten were credential checks, and 13 investigations of active problems. Eight of the 23 cases were for alcohol, eight for drug, and seven for behavioral problems. Only one person lost medical staff privileges. The committee has been well accepted by the medical staff and hospital administration and can be easily reproduced in other hospitals.

Hospital-based professional assistance committees: literature review and guidelines.

This paper presents a review of the current literature on hospital professional assistance committees, a discussion of key issues, and a set of guidelines for the design and operation of these committees. The employee assistance program is suggested as a resource to these committees.

Diagnosis and management of esophageal perforations.

Esophageal perforation remains a difficult diagnostic and management problem. Recommendations regarding treatment remain controversial. A 15-year experience with perforation of the esophagus from all causes was reviewed at Louisiana State University and Veterans Administration, Medical Centers (Shreveport, LA). The majority of the injuries involved the thoracic esophagus (28 or 54%), followed by the cervical (21 or 40%), and the intraabdominal esophagus (3 or 6%). Iatrogenic causes constituted most of the injuries (52%), followed by external trauma (23%), barogenic rupture (15%), and ingested foreign bodies (10%). Diatrizoate methylglucamine 66 per cent, sodium diatrizoate 10 per cent (Gastrografin; Squibb, Princeton, NJ) contrast studies and flexible esophagoscopy were performed in 44 and 22 patients, respectively. In the cervical esophagus, contrast studies were more sensitive and specific than endoscopy (P less than .01), but both studies were equally effective as diagnostic methods in thoracic perforations. Cervical perforations were treated with either drainage alone (7 patients) or primary repair with drainage (14 patients) with an operative mortality of 4.8 per cent. Several procedures were used in thoracic perforations, which carried a mortality of 36 per cent and were more lethal than cervical tears (P less than 0.2). Any thoracic esophageal perforation treated more than 24 hours after the onset of symptoms, irrespective of what procedure was used, was associated with a significantly higher mortality than if operated on earlier (P less than .001). Five patients with perforated carcinomas were treated by esophageal resection with no mortality. Significantly higher mortality was seen with a delay in diagnosis, thoracic perforations, and Boerhaave's Syndrome. A subset of patients with perforated carcinomas may benefit from esophageal resection with delayed reconstruction.

Calves chronically implanted with a total artificial heart as a pharmacological model.

Pharmacological therapy for congestive heart failure includes drugs that have both inotropic and vasoactive effects, although it is sometimes difficult to differentiate between the two effects. An animal with an implanted total artificial heart (TAH) allows the investigation of the vascular effect of these drugs in the absence of the effect on the myocardium. An advantage of the TAH model is its sensitivity to changes in right and left ventricular preload and afterload. Four instrumented TAH calves were given vasoactive drugs and the response was compared to control. Epinephrine, dopamine, isoproterenol, and nitroprusside were selected because of the predictability of their responses. Epinephrine caused a significant increase in systemic vascular resistance (SVR), and dopamine caused a significant increase in Pulmonary vascular resistance (PVR) and Isoproterenol caused a significant decrease in PVR. TAH implanted calves can thus serve as a pharmacological model to study the vascular response, which may be useful in investigation of new agents with inotropic and vascular effects.

Control systems for the electric heart.

Methods to predict and control cardiac output (CO) accurately in total artificial heart (TAH) recipients have varied significantly in the last few decades. Early models exhibited minimal control mechanisms and involved fixed pumping parameters. Elaborate electromechanical systems that have recently evolved require intricate communication between the circulating blood volume and the electric pump to maintain blood flow to critical organs. Attempts to quantitate specific end-organ blood flow, metabolic alterations, and oxygen delivery and, finally, to link these functions to the control of the TAH have not succeeded. Current devices seek to predict the needed CO by monitoring preload, afterload, or a combination of both. No consensus has developed concerning the appropriate physiologic parameters that should be surveyed in vivo and then used to regulate the output of the TAH.

Microbially infected thrombus in animals with total artificial hearts.

In a retrospective study of 330 animals with total artificial hearts (TAH), 103 (31%) had microbially infected thrombi (MIT). The incidence of MIT approximated 75% in the animals surviving more than 100 days. The most common pathogen isolated from animals with MIT was Pseudomonas. Most thrombi appeared to have originated from valve junctions and connectors. Methods to prevent MIT should be aimed at eliminating thrombus formation by improved design and materials and controlling the route of bacterial colonization. These findings suggest that bacterial interaction with the thrombus, device-related bacterial colonization, host immunomodulation, and gut barrier function after TAH implantation need further study.

Comparison of microsphere and intraoperative quantitation of bronchial blood flow.

Although significant variation in bronchial blood flow (BBF) has been reported, precise quantitation is difficult because of the small sized vessels and variable anatomy. Ventricular balance is critical to the function of the total artificial heart (TAH), and variation in BBF can alter this balance in the bovine model. Bronchial blood flow was measured in 12 calves by two methods: six by the radioactive labeled microsphere technique (MBBF), and six intraoperatively (IBBF) during cardiopulmonary bypass (CPB). In the MBBF group, BBF ranged from 1.9 ml/kg to 16.0 ml/kg, whereas IBBF varied from 2.6 ml/kg to 10 ml/kg (NS). Cardiac output (CO) was significantly higher (p less than 0.0005) in the MBBF group. Bronchial blood flow in both groups was highly variable. The higher flow in the MBBF group may be attributed to the arteriovenous shunting of microspheres, whereas lower flow in the IBBF group may be secondary to physiologic changes during CPB. This technique, described to measure IBBF, can estimate large variations in the natural right to left shunt that contributes to imbalance in the TAH.

Right-left ventricular output balance in the totally implantable artificial heart.

Pneumatically powered artificial hearts readily accommodated the higher net stroke volumes by the right ventricle than from the left ventricle. We published that this discrepancy was approximately 8% of the left ventricular cardiac output. A variety of methods have been used to achieve balance between the right and left atrial pressures. Relatively large volume-displacement chambers (VDC) present potential problems, but do provide balance. The VDC in volumetrically coupled right-left stroke volumes was eliminated by using a small-diameter interatrial shunt (IAS). Preliminary studies demonstrated excellent balance in contracted and expanded blood volume (preload) and by hypotension and hypertension created with vasoactive drugs (afterload). At a mean aortic pressure of 120 mmHg, heart rate of 120 BPM, cardiac output of 8 L/minute and right atrial pressure of 13 mmHg, the peak IAS flow was 3.2 ml/beat in a right to left direction and 8.0 ml/beat in a left to right direction. The net left to right flow was 4.8 ml/beat. Over a wide range of preload (2 to 20 mmHg) and afterload (45 to 180 mmHg), the left atrial pressure was routinely 5 mm Hg more than the right atrial pressure. Elimination of the VDC reduces the number of components, volume, and weight of the totally implantable artificial heart. The IAS offers a simple solution to a very complex problem and provides a device that is simpler to implant and is possible to explant.

Interspecies extrapolation of pharmacokinetics.

The purpose of this paper is to use physiologically based pharmacokinetic models to demonstrate that if toxic response is a function of the time profile in physiological time of the concentration of the toxic moiety in the target tissue, then the appropriate interspecies scaling law for toxic compounds which are metabolically deactivated is mg kg-1 per unit of physiological time (mg kg-1 pt-1). At low dose rates this metric is approximately equivalent to mg kg-0.75 day-1. For reactive metabolites which are spontaneously deactivated, an approximate interspecies scaling law is mg kg-1 day-1.

Interspecific scaling of toxicity data.

This paper reexamines the scaling approaches used in cancer risk assessment and proposes a more precise body weight scaling factor. Two approaches are conventionally used in scaling exposure and dose from experimental animals to man: body weight scaling (used by FDA) and surface area scaling (BW0.67--used by EPA). This paper reanalyzes the Freireich et al. (1966) study of the maximum tolerated dose (MTD) of 14 anticancer agents in mice, rats, dogs, monkeys, and humans, the dataset most commonly cited as justification for surface area extrapolation. This examination was augmented with an analysis of a similar dataset by Schein et al. (1970) of the MTD of 13 additional chemotherapy agents. The reanalysis shows that BW0.75 is a more appropriate scaling factor for the 27 direct-acting compounds in this dataset.

A study of the odontoblast process with transmission electron microscopy.

Freshly extracted human third molars with completely formed roots were sectioned and placed in Karnovsky's fixative. The specimens were decalcified in ethylenediaminetetraacetic acid (EDTA) for 91 days, followed by digestion in collagenase. They were then fixed in a solution of buffered osmium tetroxide or ruthenium red and buffered osmium tetroxide, embedded in Spurr's plastic mixture, and sectioned for transmission electron microscopy. Each section was stained with uranyl acetate and lead citrate and viewed with a transmission electron microscope. No odontoblast processes could be identified at the cemental third of the dentin with the described technique.

Leukotrienes: inflammatory mediators--a review.

This article reviews a group of inflammatory mediators called leukotrienes. It includes their historical background, chemical pathway of formation, presence in cells and fluids, and biologic activity. These potent substances may be involved in pulpal and periradicular disease, but such involvement has not yet been reported.