Development of an x-ray radiography platform to study laser-direct-drive energy coupling at the National Ignition Facility.

A platform has been developed to study laser-direct-drive energy coupling at the National Ignition Facility (NIF) using a plastic sphere target irradiated in a polar-direct-drive geometry to launch a spherically converging shock wave. To diagnose this system evolution, eight NIF laser beams are directed onto a curved Cu foil to generate Heα line emission at a photon energy of 8.4 keV. These x rays are collected by a 100-ps gated x-ray imager in the opposing port to produce temporally gated radiographs. The platform is capable of acquiring images during and after the laser drive launches the shock wave. A backlighter profile is fit to the radiographs, and the resulting transmission images are Abel inverted to infer radial density profiles of the shock front and to track its temporal evolution. The measurements provide experimental shock trajectories and radial density profiles that are compared to 2D radiation-hydrodynamic simulations using cross-beam energy transfer and nonlocal heat-transport models.

High-yield magnetic recoil neutron spectrometer on the National Ignition Facility for operation up to 60 MJ.

Recent progress at the National Ignition Facility (NIF), with neutron yields of order 1 × 1017, places new constraints on diagnostics used to characterize implosion performance. The Magnetic Recoil neutron Spectrometer (MRS), which is routinely used to measure yield, ion temperature (Tion), and down-scatter ratio (dsr), has been adapted to allow measurements of dsr up to 5 × 1017, and yield and Tion up to 2 × 1018 in the near term with new data processing techniques and conversion foil solutions. This paper presents a solution for extending MRS operation up to a yield of 2 × 1019 (60 MJ) by moving the spectrometer outside of the NIF shield wall. This will not only enhance the upper yield limit by 10× but also improve signal-to-background by 5×.

Temporary abolition of pain in man.

In eight patients with intense chronic cutaneous pain, sensory nerves or roots. supplying the painful area were stimulated. Square-wave 0.1-millisecond pulses at 100 cycles per second were applied, and the voltage was raised until the patient reported tingling in the area. During this stimulation, pressure on previously sensitive areas failed to evoke pain. Four patients, who had diseases of their peripheral nerves, experienced relief of their pain for more than half an hour after stimulation for 2 minutes.

Differentiated rat glial cell strain in tissue culture.

Rat glial tumors, induced by injections of N-nitrosomethylurea, were plated and propagated in culture. Among a few cell strains obtained, one clone contains S-100 protein, which is unique to brain in vertebrates. Stationary-phase cultures contain approximately ten times more S-100 protein per cell than exponentially growing cells. When injected into newborn rats, cells producing S-100 grew as a glial tumor, which contained S-100 protein.

Ozone selectively inhibits growth of human cancer cells.

The growth of human cancer cells from lung, breast, and uterine tumors was selectively inhibited in a dose-dependent manner by ozone at 0.3 to 0.8 part per million of ozone in ambient air during 8 days of culture. Human lung diploid fibroblasts served as noncancerous control cells. The presence of ozone at 0.3 to 0.5 part per million inhibited cancer cell growth 40 and 60 percent, respectively. The noncancerous lung cells were unaffected at these levels. Exposure to ozone at 0.8 part per million inhibited cancer cell growth more than 90 percent and control cell growth less than 50 percent. Evidently, the mechanisms for defense against ozone damage are impaired in human cancer cells.

Plasma membrane lipid composition modulates action of anesthetics.

The effect of LM fibroblast plasma membrane phospholipid composition on the selectivity of charged amphipathic anesthetics for exofacial or cytofacial leaflets was examined. Because preference of charged amphipaths for one of the plasma membrane bilayer leaflets may be conferred by net changes in the polar headgroup composition, LM fibroblasts were cultured in the presence of choline or N-demethylated analogs in order to change this polar headgroup composition. These altered bases were incorporated into plasma membrane phospholipids. A significant difference in 1,6-diphenyl-1,3,5-hexatriene (DPH) limiting anisotropy was observed between plasma membrane leaflets of phosphatidylcholine-, but not phosphatidylethanolamine-enriched cells. Phenobarbital, which preferentially decreased the limiting anisotropy of 1,6-diphenyl-1,3,5-hexatriene in the exofacial leaflet, had little or no preferential effect in phosphatidyl-N,N-dimethylethanolamine-enriched membranes. Prilocaine preferentially reduced the limiting anisotropy of 1,6-diphenyl-1,3,5-hexatriene in the exofacial leaflet in phosphatidyl-N-methylethanolamine-enriched membranes, exactly opposite to its effect in phosphatidylcholine-enriched membranes. In contrast, prilocaine had no selective effect in phosphatidylethanolamine-enriched membranes. In summary, the phospholipid polar headgroup composition can dramatically affect the selectivity of charged amphipathic anesthetics in altering the limiting anisotropy, a measure of restriction to motion of 1,6-diphenyl-1,3,5-hexatriene, in individual monolayers.

Regulation of transbilayer distribution of a fluorescent sterol in tumor cell plasma membranes.

The lipid composition and transbilayer distribution of plasma membrane isolated from primary tumor (L-929, LM, A-9 and C3H) and nine metastatic cell lines cultured under identical conditions was examined. Cultured primary tumor and metastatic cells differed two-fold in sterol/phospholipid molar ratios. There was a direct correlation between plasma membrane anionic phospholipid (phosphatidylinositol and phosphatidylserine) content and plasma membrane sterol/phospholipid ratio. This finding may bear on the possible link between oncogenes and inositol lipids. The fluorescent sterol, dehydroergosterol, was incorporated into primary tumor and metastatic cell lines. Selective quenching of outer monolayer fluorescence by covalently linked trinitrophenyl groups demonstrated an asymmetric transbilayer distribution of sterol in the plasma membranes. The inner monolayer of the plasma membranes from both cultured primary and metastatic tumor cells was enriched in sterol as compared with the outer monolayer. Consistent with this, the inner monolayer was distinctly more rigid as determined by the limiting anisotropy of 1,6-diphenyl-1,3,5-hexatriene. Dehydroergosterol fluorescence was temperature dependent and sensitive to lateral phase separations in phosphatidylcholine vesicles and in LM cell plasma membranes. Dehydroergosterol detected phase separations near 24 degrees C in the outer monolayer and at 21 degrees C and 37 degrees C in the inner monolayer of LM plasma membranes. Yet, no change in transbilayer sterol distribution was detected in ascending or descending temperature scans between 4 and 45 degrees C. Alterations in plasma membrane phospholipid polar head group composition by choline analogues (N,N-dimethylethanolamine, N-methylethanolamine, and ethanolamine) also did not perturb transbilayer sterol asymmetry. Treatment with phenobarbital or prilocaine, drugs that selectively fluidize the outer and inner monolayer of LM plasma membranes, respectively, did not change dehydroergosterol transbilayer distribution.

Late arterial responses (6 and 12 months) after (32)P beta-emitting stent placement: sustained intimal suppression with incomplete healing.

BACKGROUND: Three-month studies of stent-delivered brachytherapy in the rabbit model show reduced neointimal growth. However, intimal healing is delayed, raising the possibility that intimal inhibition is merely delayed rather than prevented. The purpose of this study was to explore the long-term histological changes after placement of beta-emitting radioactive stents in normal rabbit iliac arteries. METHODS AND RESULTS: Three-millimeter beta-emitting (32)P stents (6, 24, and 48 microCi) were placed in normal rabbit iliac arteries with nonradioactive stents as controls. Animals were euthanatized at 6 and 12 months, and histological assessment, morphometry, and analysis of endothelialization were performed. Morphometric measurements demonstrated a >50% reduction in intimal growth and percent lumen stenosis within 24- and 48-microCi stents versus control nonradioactive stents at both 6 and 12 months. However, the 24- and 48-microCi stents also showed delayed healing of the intimal surface, characterized by persistent fibrin thrombus with nonconfluent areas of matrix, incomplete endothelialization, and increased intimal cellular proliferation. Stent edge stenosis was present at 12 months in the 24- and 48-microCi stent groups, characterized by both intimal thickening and negative arterial remodeling. CONCLUSIONS: Inhibition of intimal growth is maintained 6 and 12 months after (32)P beta-emitting stent placement. However, delayed arterial healing, incomplete endothelialization, and edge effects are present.

Mechanical unloading restores beta-adrenergic responsiveness and reverses receptor downregulation in the failing human heart.

BACKGROUND: Mechanical unloading of the failing human heart with a left ventricular assist device (LVAD) results in clinically documented reversal of chamber dilation and improvement of cardiac function. We tested the hypothesis that LVAD support normalizes the ability of cardiac muscle to respond to sympathetic nervous system stimulation by reversing the downregulation of beta-adrenergic receptors. METHODS AND RESULTS: Human LV tissue was obtained from nonfailing hearts of unmatched organ donors and failing hearts at the time of transplantation, with or without LVAD. Baseline contractile parameters and inotropic response to a beta-adrenergic agonist were measured in isolated trabecular muscles. beta-Adrenergic receptor density was quantified by radioligand binding. Results showed a significant increase in the response to beta-adrenergic stimulation after LVAD (developed tension increased by 0.76+/-0.09 g/mm(2) in nonfailing, 0.38+/-0.07 in failing, and 0.68+/-0.10 in failing+LVAD; P<0.01), accompanied by an increased density of beta-adrenergic receptors (58.7+/-9.6 fmol/mg protein in nonfailing, 26.2+/-3.8 in failing, and 63.0+/-8.3 in failing+LVAD; P<0.05). These changes were unrelated to the duration of support. CONCLUSIONS: Data demonstrate that mechanically supporting the failing human heart with an LVAD can reverse the downregulation of beta-adrenergic receptors and restore the ability of cardiac muscle to respond to inotropic stimulation by the sympathetic nervous system. This indicates that functional impairment of cardiac muscle in human heart failure is reversible.

Sodium and volume depletion activates neurogenic mechanisms in renal hypertensive dogs.

The acute response to ganglionic blockade (hexamethonium bromide, 30 mg/kg, i.v.) was used to evaluate the neurogenic contributions to mean arterial pressure maintenance in the conscious one-kidney, one clip hypertensive dog. Approximately 2 hours (112 minutes) after ganglionic blockade, captopril (10 mg/kg, i.v.) was given to block the renin-angiotensin system. Hypertensive animals were studied 3 days after clipping (group 2) or 2 to 4 weeks after clipping (groups 3 and 4). Groups 2 and 3 were fed a regular sodium diet, but group 4 animals were sodium and volume depleted. Normotensive control animals (group 1) were fed a regular sodium diet. On the day of the acute experiment the baseline blood pressures measured in group 2 (151 +/- 10 mm Hg, n = 5), group 3 (154 +/- 5 mm Hg, n = 7), and group 4 (160 +/- 8 mm Hg, n = 7) were not different (p greater than 0.05) from each other, but all were elevated (p less than 0.05) compared with the group 1 animals (106 +/- 3 mm Hg, n = 8). Also, there were no significant differences (p greater than 0.05) in the baseline plasma catecholamine levels among the three hypertensive groups. Ganglionic blockade produced a greater fall in blood pressure (p less than 0.05) in the sodium/volume-depleted dogs of group 4 (-35 mm Hg) than in group 1 (-10 mm Hg), group 2 (-3 mm Hg), or group 3 (-12 mm Hg) animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Polyunsaturated fatty acids alter sterol transbilayer domains in LM fibroblast plasma membrane.

Sterols are asymmetrically distributed between the leaflets of animal cell plasma membranes. Although transbilayer migration of sterols is extremely rapid, s to min, previous experimental manipulations have not altered their transmembrane steady-state distribution. However, the effect of polyunsaturated fatty acids has not been reported. When cultured in a lipid-free, chemically defined culture medium, LM fibroblasts do not synthesize polyunsaturated fatty acids but will incorporate polyunsaturated fatty acids into their plasma membranes if supplied in the medium. Sterol transbilayer distribution in LM plasma membranes was determined from quenching of fluorescence of dehydroergosterol by trinitrophenyl groups selectively attached to the exofacial leaflet. When cells are cultured in lipid-free media, 28.1% of the plasma membrane sterol is located in the exofacial (outside) leaflet. In contrast, when cells are cultured with linoleate- or linolenate-supplemented medium, 71.8% and 75.5% of the plasma membrane sterol is exofacial, respectively.

Pre-trigeminal neuralgia.

Eighteen patients who subsequently developed typical trigeminal neuralgia experienced a prodromal pain termed "pre-trigeminal neuralgia." These patients described their prodromal pain as a toothache or sinusitis-like pain lasting up to several hours, sometimes triggered by jaw movements or by drinking hot or cold liquids. Typical trigeminal neuralgia developed a few days to 12 years later, and in all cases affected the same division of the trigeminal nerve. Six additional patients experiencing what appeared to be pre-trigeminal neuralgia became pain-free when taking carbamazepine or baclofen. Recognition of pretrigeminal neuralgia makes it possible to relieve the pain with appropriate medications and avoid unnecessary irreversible dental procedures.

Neointimal responses 3 months after (32)P beta-emitting stent placement.

PURPOSE: Studies have shown a potential benefit of brachytherapy in preventing restenosis. However, the effects of intravascular radiation on arterial healing have not been well-established. The purpose of this study was to explore the histologic changes following placement of beta-emitting radioactive stents in arteries focusing on intimal responses and endothelialization. METHODS AND MATERIALS: 3.0-mm beta-emitting (32)P stents (6-microCi and 24-microCi) were placed in rabbit iliac arteries with nonradioactive stents serving as controls. Animals were euthanized at 3 months and histologic assessment, morphometry, and analysis of endothelialization were performed. RESULTS: The lumen areas of 24-microCi stents (4.24 +/- 0.22 mm(2), p < 0.0007) and 6-microCi stents (4.23 +/- 0.49 mm(2), p < 0.01) were larger than control stents (3.64 +/- 0.44 mm(2)). The mean lumen percent stenosis was 11. 4 +/- 3.0% in the 24-microCi stents (p < 0.007 vs. 6-microCi stents and p < 0.0001 vs. control stents), 18.7 +/- 6.4% in the 6-microCi stents (p < 0.02 vs. control stents), and 25.0 +/- 4.9% in control stents. Neointimal area was least in the 24-microCi stent (54.2% smaller than controls and 42.7% smaller than 6-microCi); the neointimal area of the 6-microCi stents was 20.0% less than controls. The control stent neointima consisted of smooth muscle cells in a proteoglycan and collagen matrix. In contrast, the intima of radioactive stents showed persistent fibrin thrombus with nonconfluent areas of matrix. Actin-positive intimal cell density was reduced with radioactive stenting, but intimal cell proliferation was increased. Evans blue staining, an indicator of increased endothelial permeability, was present on 86 +/- 9% of the stented segment of 6-microCi stents vs. 10 +/- 11% in controls (p < 0.0001). Scanning electron microscopy demonstrated endothelialization of 97 +/- 8% of the intimal surface of control stents; in contrast, the midportion of the 6-microCi stents remained nonendothelialized, and only 33 +/- 15% (p < 0.0001) of the entire stent surface was endothelialized. CONCLUSIONS: (32)P beta-emitting stents reduce neointimal growth, but healing is incomplete with poor endothelialization at 3 months. Longer-term studies with complete arterial healing are needed to determine whether there is sustained neointimal inhibition by stent-delivered brachytherapy.

The 90-day coronary vascular response to (90)Y-beta particle-emitting stents in the canine model.

PURPOSE: Long-term preclinical studies using continuous, low-dose-rate vascular brachytherapy with (32)P beta-emitting stents have yielded largely disappointing results. In contrast, a shorter half-life, higher dose-rate (90)Y beta-emitting stent more closely mimics the delivery dose rate characteristics of clinically effective beta- and gamma-wire and balloon brachytherapy devices. We evaluated the dose response characteristics of a (90)Y beta-emitting stent in the canine coronary injury model and hypothesized that this device would reduce neointimal formation. METHODS: Seventy-seven (90)Y beta-emitting coronary stents (15 mm BXTM, 3.0- and 3.5-mm diameter) were implanted in 26 normal dogs (20-25 kg) using a randomized, blinded study design. Stent activity included nonradioactive controls (n = 24), 4.5 microCi (n = 15), 8 microCi (n = 12), 16 microCi (n = 18), and 32 microCi (n = 8). Histologic endpoints were assessed at 3 months. RESULTS: Luminal stenosis and neointimal area were similar in control stents and low-activity (4.5 and 8 microCi) (90)Y stents. Higher activity stents (16 and 32 microCi) were associated with significant adverse effects. Frequent total occlusions (5 of 18 stents, 28%; p = 0.008) and a 40% increase in neointimal area (p = 0.024 vs. control) occurred in the 16 microCi group. Incomplete neointimal healing and a trend for reduced neointimal cell density were evident only in the 16- and 32-microCi group. CONCLUSION: Despite unique characteristics (2.7 day half-life and a higher dose rate) of (90)Y beta-emitting coronary stents, they have an adverse effect on neointimal formation, including frequent total occlusions at high activity levels. Incomplete healing, present 90 days (33 half-lives) after stent placement, indicates prolonged recovery from radiation injury.

Deafferentation pain after posterior rhizotomy, trauma to a limb, and herpes zoster.

After incisional or alcoholic destruction of trigeminal posterior rootlets, constant dysesthesias of major degree referred to some part of the markedly denervated zone develop in 5 to 15% of the patients. The full severity may not appear for weeks or months. There is no allodynia or hyperpathia of the denervated zone. Bulbar trigeminal tractotomy with sparing of touch sensation produces severe dysesthesias in a tiny percentage of the patients, as does selective destruction of pain fibers by radiofrequency heating or glycerol. Spinal posterior rhizotomy elicits in less than 4% a lasting dysesthesia entirely different in temporal sequence, locus, and type of pain: (a) it tends to be maximal early after operation and to improve, (b) the spontaneous pain is accompanied by severe allodynia, and (c) the pain is usually referred beyond the margins of the insentient (rhizotomized) zone and may even be referred to the corresponding area on the opposite side. Sindou's "selective posterior rhizotomy," i.e., cutting of the small fiber lateral component of each rootlet as it enters the cord, has not given rise to dysesthesias. These do occur briefly in 50% of the cases following spinal ganglionectomy, the sensations being referred to the dermatomal segment of the ganglion in question. The secondary afferent neurons in the mesencephalic, principal, oral, and interpolar nuclei for the trigeminal posterior roots have no counterpart in the spinal cord for the spinal posterior roots. We suggest that the explanation for the fact that neither trigeminal neuralgia nor trigeminal anesthesia dolorosa have a spinal clinical counterpart is related to the as yet unexplained special functions of the elaborate trigeminal secondary afferent neuronal apparatus.(ABSTRACT TRUNCATED AT 250 WORDS)

Entrapment of the C2 root and ganglion by the atlanto-epistrophic ligament: clinical syndrome and surgical anatomy.

Two cases of progressive, occipital lancinating pain and dysesthesias associated with a sensory deficit of the C2 dermatome are presented. Symptoms were relieved, and C2 sensory function restored by releasing a hypertrophied atlanto-epistrophic ligament entrapping the C2 root and ganglion. The normal anatomy and abnormal surgical findings are described. C2 entrapment by the atlanto-epistrophic ligament is discussed in reference to other C2 lesions causing occipital pain. We conclude that some patients whose progressive occipital pain is accompanied by a C2 sensory deficit are suffering from entrapment of the C2 root and ganglion amenable to surgical decompression.