Inhibition of turbulence in inertial-confinement-fusion hot spots by viscous dissipation.

Achieving ignition in inertial confinement fusion (ICF) requires the formation of a high-temperature (>10 keV) central hot spot. Turbulence has been suggested as a mechanism for degrading the hot-spot conditions by altering transport properties, introducing colder, mixed material, or reducing the conversion of radially directed kinetic energy to hot-spot heating. We show, however, that the hot spot is very viscous, and the assumption of turbulent conditions in the hot spot is incorrect. This work presents the first high-resolution, three-dimensional simulations of National Ignition Facility (NIF) implosion experiments using detailed knowledge of implosion dynamics and instability seeds and including an accurate model of physical viscosity. We find that when viscous effects are neglected, the hot spot can exhibit a turbulent kinetic energy cascade. Viscous effects, however, are significant and strongly damp small-scale velocity structures, with a hot-spot Reynolds number in the range of only 10-100.

Improvement of motor function in multiple sclerosis by use of protopam chloride.

PAM, a cholinesterase reactivator, was administered orally and parenterally to 37 patients with multiple sclerosis and a control group of 24 patients with other neurological diseases and pain syndromes. The effects of the administration of this compound in these patients with and without electrical stimulation of the spinal cord were studied. The clinical response to the drug follows a known time course and is dose related. Administration of large doses orally or intravenously aggravates existing neurological dysfunction. With a dose of 1,000 mg intravenously, a characteristic response is the temporary appearance of new ophthalmological abnormalities, followed by significant improvement in motor control and behavior, which gradually subsides. Parenteral administration is superior to oral. Tolerance to the drug is observed. The presence of electrical stimulation of the spinal cord complements the action of the drug. When electrical stimulation is withdrawn, the effect of the drug reproduces the effect of the electrical stimulation. It is suggested there is a defect in cholinesterase in multiple sclerosis patients, and its reactivation may have a significant relationship to signs and symptoms.

Growth of astrocytomas in the human tumor clonogenic assay and sensitivity to mismatched dsRNA and interferons.

Nine astrocytoma specimens were received from seven patients and processed for testing in the human tumor clonogenic assay (HTCA). Cells derived from these specimens were challenged with human natural alpha-interferon (alpha-IFN) and beta interferon (beta-IFN), recombinant beta interferon (beta ser-IFN), and mismatched double-stranded (ds) RNA (Ampligen). Six of the astrocytoma specimens formed adequate colonies for drug sensitivity testing (greater than or equal to 30 colonies/plate), and all were high-grade (III-IV) tumors. Sensitivity was defined as a greater than or equal to 50% decrease in tumor colony formation following drug exposure and was observed with alpha-IFN (2/4), beta-IFN (3/4), and mismatched dsRNA (4/5) exposure. No decrease in colony growth was observed after recombinant beta ser-IFN exposure, and in 2 of 3 cases, colony formation was stimulated. The sensitivity of 75 non-CNS solid tumors to mismatched dsRNA was compared to the high-grade astrocytomas in the HTCA. Of the 10 additional histologic tumor types studied, carcinoid and renal cell carcinomas exhibited the greatest sensitivity to mismatched dsRNA: 63% and 52%, respectively. However, in comparison, 80% of the high-grade astrocytomas were sensitive, demonstrating that these gliomas are among the most sensitive of human tumors to mismatched dsRNA in vitro. Clinical trials of interferons and mismatched dsRNA, coupled with in vitro sensitivity studies, should further define their therapeutic potential.

Human non-malignant and malignant brain tumor derived cell cultures: proliferation and sensitivity to natural human fibroblast (beta) interferon.

Twenty-one human brain tumor biopsies were processed by mechanical and enzymatic methods to produce mixed cell suspensions. Cultures were prepared in small plastic flasks, and primary outgrowth occurred in 16/21 cultures. The period required for primary outgrowth ranged from 3 days to 14 days. We established serial propagation with 15/16 of the primary cultures. Sensitivity to HuIFN-beta was determined between passages 3 to 12, using a microassay based on cell viability (uptake of a supravital stain, neutral red). Extracted dye was quantified in acidic-methanol using the MR580 Microelisa Autoreader (Dynatech). We observed a broad range of responsiveness to the drug among the 12 cell-strains tested. Thus, 4 cell strains were relatively sensitive; 4 were resistant to 10(4) IRU/ml of purified HuIFN-beta. Four cell strains exhibited a level of responsiveness that was intermediate to that of these two groups. During propagation of these biopsies, cytopathology suggestive of paramyxovirus-infection appeared in 4 of the cell-strains. This characteristic was not uniformly associated with high sensitivity to human beta interferon which is a very potent, naturally occurring antiviral substance. Our results support the concept that information concerning sensitivity to HuIFN-beta and other cytostatic agents may be rapidly obtained using microcultures of brain tumor cultures in conjunction with supravital stain uptake studies. Additionally, these results suggest that further clinical studies with beta interferon should be undertaken to define the parameters which determine successful in vivo application.

Serum protein masking of the thermal sensitivity of the antiviral activity of purified human beta interferon: implications for clinical studies.

Human beta-interferon (HuIFN-beta) exhibits antiproliferative and antiviral properties. Successful clinical application of this drug depends on knowledge of the thermal stability of these activities under physiological conditions. In the present study, both the antiproliferative and antiviral activities were stabilized by the addition of very small quantities of serum proteins. This supplement was sufficient to mask the slightly higher thermosensitivity of the antiviral activity. In the absence of serum proteins, the values of both the half-life and the energy of activation were higher for the antiproliferative activity than for the antiviral function. Each had a half-life of at least 24 h and identical values for the energy of activation in the presence of proteins furnished by 1% fetal bovine serum. This study provides additional evidence to support a thesis recently advanced by Carter et al. that the antiproliferative domain of glycosylated beta interferon may be separable from the antiviral domain. It is concluded that the efficacy of HuIFN-beta, under clinical conditions, will not be seriously impaired by thermal inactivation. Antiviral assays of serum may be freely substituted for antiproliferative assays during pharmacological studies.

Sensory effects in man of lesions of the posterior columns and of some other afferent pathways.

Clinical observations are presented on the sensory effects of lesions of different afferent pathways of the spinal cord, correlated whenever possible with histological evidence of the location and extent of the lesions. They are based on personal cases and on significant cases in the literature, including posterior column section, other causes of damage to the posterior columns, and cases of commissural myelotomy. It is concluded that the traditional view of the effects of lesions of the posterior columns is correct, but that evidence from cases proved by postmortem examination is still needed. When the information normally supplied by the posterior columns is cut off, primary sensibility for light touch and pressure is not lost, but any kind of discrimination is disturbed. There is also a disturbance in knowledge of movement and position, ataxia, and clumsiness in the use of the hands. These defects greatly affect the palpatory examination of objects and, although they may appear slight on routine neurological examination, they can cause severe disturbances in the activities of daily living. For tactile modalities, a lesion of the spinothalamic complex causes minimal or no defects and a lesion of the posterior columns causes only slight defects, whereas a lesion of both pathways gives rise to total loss of tactile and pressure sensibility in the part of the body served by both pathways. This conclusion is based on 2 cases with combined commissural myelotomy and anterolateral cordotomy. The following disturbances of mechanoreception attributed to lesions of the posterior columns are discussed: lability of threshold, persistence of sensation, tactile and postural hallucinations and temporal and spatial disturbances. In man, lesions of the posterior columns cause an increase in pain, tickle, warmth and cold. Cases are presented with and without lesions of the posterolateral columns in conjunction with lesions of one or both anterolateral columns. As these lesions did not affect sensation and as there was no difference in the sensory state following anterolateral cordotomies with or without involvement of the posterolateral column, it is concluded that lesions of this column have no effect on sensation. Cases with lesions of the anterior two-thirds of the cord are also presented to illustrate the sensory state with only the posterior third of the cord intact. In these cases, tactile and pressure sensibility and knowledge of movement and position are normal.

Sensory consequences of commissural myelotomy. A challenge to traditional anatomical concepts.

Twenty-five cases of commissural myelotomy were studied. Representative cases are reported, including a histological examination of the lesion in one. Although the purpose of the operation is to produce a cuirass of loss of pain sensibility by dividing the spinothalamic and spinoreticulothalamic fibres as they decussate in the anterior commissure of the cord, this result is not always obtained. Whether or not the expected sensory loss is obtained, the chronic pain for which the operation is performed can be relieved. Sensibility tends to return towards normal after myelotomy. Even with substantial recovery of sensory loss, the pain for which the operation was performed can remain absent. Asymmetrical sensory loss may be produced by the operation; reasons for this are suggested. Differences between the results of commissural myelotomy and anterolateral cordotomy are discussed. Unlike the results of anterolateral cordotomy, which can be accounted for on the basis of known anatomy, the results of commissural myelotomy are inexplicable on present anatomical knowledge. Attention is drawn to the results of myelotomy reported originally by Hitchcock and confirmed by other neurosurgeons in which a short myelotomy incision in the upper cervical cord caused loss of pain over a vast region of the body. The difficulty in explaining the patterns of sensory loss in these cases is discussed. The literature on pathways alternative to the spinothalamic and spinoreticulothalamic is reviewed. It is argued that the central incision cannot cause relief of pain merely by cutting an afferent pathway, and it is suggested that this lesion blocks impulses entering into, in, or leaving the spinothalamic complex. The accurate localization of pinprick and thermal stimuli via the spinothalamic tract is demonstrated.

Human brain tumor--derived cell lines: growth rate reduced by human fibroblast interferon.

The biological response modifier human beta-interferon had pronounced antigrowth effects on various histologic types of human brain tumor cells but no effects on a nontransformed cell line, MRC-5. The cultures of brain tumor cells showed severe alterations indicative of cell injury and death after exposure to beta-interferon for 2 to 6 days. Similar results were obtained with cells freshly explanted from human brain tumors. The results indicate that it may be possible to use fresh, explanted tumor tissue to identify patients who might benefit from therapy with beta-interferon.

Sitting prone position for the posterior surgical approach to the spine and posterior fossa.

The sitting prone position is compared with the standard laminectomy prone position and the sitting up position for posterior fossa surgery. We measured central venous pressure and airway pressure with the patient in different positions to determine the comparative efficacy of the sitting prone position. On a linear average, the central venous pressure increased by 6.83 cm H2O and the airway pressure increased by 3.16 cm H2O when the patient was changed from the supine to the standard prone position under general anesthesia; with a change from the standard prone position to the sitting prone position, the central venous pressure decreased by 10.45 cm H2O and the airway pressure decreased by 3.66 cm H2O. However, comparing the sitting prone position for posterior fossa surgery with the sitting up position, there was no statistically significant difference in central venous or airway pressure.

Functional stimulation of the spinal cord in multiple sclerosis.

The authors describe the effect of electrical stimulation of the spinal cord in multiple sclerosis. After considering the nature of multiple sclerosis, the authors describe the background, character, mode and method of delivering electrical fields to the spinal cord. The results of this form of treatment and the implications of these observations in terms of physiologic mechanisms are discussed.