Highly efficient star formation in NGC 5253 possibly from stream-fed accretion.

Gas clouds in present-day galaxies are inefficient at forming stars. Low star-formation efficiency is a critical parameter in galaxy evolution: it is why stars are still forming nearly 14 billion years after the Big Bang and why star clusters generally do not survive their births, instead dispersing to form galactic disks or bulges. Yet the existence of ancient massive bound star clusters (globular clusters) in the Milky Way suggests that efficiencies were higher when they formed ten billion years ago. A local dwarf galaxy, NGC 5253, has a young star cluster that provides an example of highly efficient star formation. Here we report the detection of the J = 3→2 rotational transition of CO at the location of the massive cluster. The gas cloud is hot, dense, quiescent and extremely dusty. Its gas-to-dust ratio is lower than the Galactic value, which we attribute to dust enrichment by the embedded star cluster. Its star-formation efficiency exceeds 50 per cent, tenfold that of clouds in the Milky Way. We suggest that high efficiency results from the force-feeding of star formation by a streamer of gas falling into the galaxy.

Nanosecond X-Ray Photon Correlation Spectroscopy on Magnetic Skyrmions.

We report an x-ray photon correlation spectroscopy method that exploits the recent development of the two-pulse mode at the Linac Coherent Light Source. By using coherent resonant x-ray magnetic scattering, we studied spontaneous fluctuations on nanosecond time scales in thin films of multilayered Fe/Gd that exhibit ordered stripe and Skyrmion lattice phases. The correlation time of the fluctuations was found to differ between the Skyrmion phase and near the stripe-Skyrmion boundary. This technique will enable a significant new area of research on the study of equilibrium fluctuations in condensed matter.

Observation of deflection of a beam of multi-GeV electrons by a thin crystal.

We report on an experiment performing channeling and volume reflection of a high-energy electron beam using a quasimosaic, bent silicon (111) crystal at the End Station A Test Beam at SLAC. The experiment uses beams of 3.35 and 6.3 GeV. In the channeling orientation, deflections of the beam of 400 µrad for both energies with about 22% efficiency are observed, while in the volume-reflection orientation, deflection of the beam by 120 µrad at 3.35 GeV and by 80 µrad at 6.3 GeV is observed with 86%-95% efficiency. Quantitative measurements of the channeling efficiency, surface transmission, and dechanneling length are taken. These are the first quantitative measurements of channeling and volume reflection using a primary beam of multi-GeV electrons.

Demonstration of single-crystal self-seeded two-color x-ray free-electron lasers.

A scheme for generating two simultaneous hard-x-ray free-electron laser pulses with a controllable difference in photon energy is described and then demonstrated using the self-seeding setup at the Linac Coherent Light Source (LCLS). The scheme takes advantage of the existing LCLS equipment, which allows two independent rotations of the self-seeding diamond crystal. The two degrees of freedom are used to select two nearby crystal reflections, causing two wavelengths to be present in the forward transmitted seeding x-ray pulse. The free-electron laser system must support amplification at both desired wavelengths.

Effects of glucose and sorbitol on proliferation of cultured human skin fibroblasts and arterial smooth-muscle cells.

To determine effects of metabolic abnormalities associated with diabetes mellitus on proliferation of diploid human cells, cultured human skin fibroblasts and arterial smooth-muscle cells were grown in media containing added glucose in the range often seen in diabetic subjects (10 to 30 mM, 180 to 550 mg./dl.). "High" glucose media enhanced proliferation of fibroblasts, with an "optimal" response at about 18 mM (325 mg./dl.). Equimolar sorbitol gave similar results, with the greatest increase in proliferation occurring at about the same concentration as for glucose (1 mM). Since neither equimolar mannitol nor sucrose produced such effects consistently, these results cannot be explained solely on the basis of hyperosmolarity. In contrast, arterial smooth-muscle cells failed to show a consistent growth response in the presence of either added glucose or sorbitol. These results suggest that studies with cultured human cells may be useful in assessment of responses to components of the disordered metabolic milieu of diabetes. Such studies of arterial smooth-muscle cells should also be useful for investigation of the mechanism of atherosclerosis in diabetes.

HIV-1 immunogen induction of HIV-1-specific delayed-type hypersensitivity: results of a double-blind, adjuvant-controlled, dose-ranging trial.

OBJECTIVE: To investigate the capacity of an HIV-1 immunogen to induce or augment HIV-1-specific delayed-type hypersensitivity (DTH) over a range of doses in asymptomatic HIV-1-seropositive adults. DESIGN: A single center, double-blind, adjuvant-controlled, dose-ranging trial involving 48 HIV-1-seropositive asymptomatic patients. Each dose group consisted of 12 subjects, eight receiving HIV-1 immunogen and four incomplete Freund's adjuvant (IFA). The doses studied were 50, 100, 200, or 400 micrograms (total protein). The HIV-1 immunogen was administered intramuscularly every 4 weeks for 36 weeks, with dosing contingent on the lack of an HIV-1 immunogen DTH response. A maximum of six doses was permitted. METHODS: Immunogenicity was assessed every 4 weeks by DTH skin testing to the inactivated HIV-1 antigen in saline with > 9 mm induration representing a response to immunization. Changes in p24-antibody levels were determined by endpoint titration using an enzyme-linked immunosorbent assay and Western blot. RESULTS: At doses of > or = 100 micrograms, all treated patients demonstrated significant differences in the ability to mount an HIV-1-specific cell-mediated response relative to adjuvant controls. Dose-related response patterns were observed in the period between doses and the occurrence of rises in HIV-1 DTH. Treatment appeared to increase p24-antibody titers as well as reactivities to other HIV-1 antigens as determined by Western blots. The HIV-1 immunogen was well tolerated. CONCLUSIONS: The minimum dose of the HIV-1 immunogen in IFA required to induce HIV-1 DTH relative to the IFA control group was 100 micrograms in this patient population.

Ethosuximide dosage regimens.

A study was conducted in 9 children with petit mal epilepsy to compare the plasma levels of ethosuximide after divided daily administration with those after single daily administration. The children received their previously established dose in divided doses for 4 wk, single morning doses for 4 wk, and again in divided doses for 4 wk. None of the children suffered petit mal seizures during the study. Three had grand mal seizures but the frequency did not differ between the dosage regimens. Plasma levels during the single-dose period peaked more rapidly and fell more quickly than during the other periods, but mean levels remained in the therapeutic range. The mean half-life of the drug in these children was 29 hr. For reasons not understood, plasma levels generally were lower in the second divided dose period than in the other two periods. No adverse experiences were reported during the study. The data indicate that ethosuximide is clinically effective when given in a single daily dose. This regimen offers advantages in convenience and possibly in patient compliance.

Effect of dietary fructose on triglyceride transport and glucoregulatory hormones in hypertriglyceridemic men.

Effects of dietary fructose on triglyceride metabolism and on basal levels and meal responses of glucose, insulin, and glucagon were studied in six hypertriglyceridemic men, two of whom were also diabetic. Constant composition, weight-maintaining formula diets were used with substitution of fructose for 20% of the carbohydrate calories in both fat-containing (45% carbohydrate) and fat-free (85% carbohydrate) periods; each of the four dietary periods was at least 2 weeks long in every subject. No effect of fructose on fasting levels of triglycerides could be seen in any of the diets. No alterations of triglyceride transport occurred with fructose substitution in the fat-containing diets, but significant reductions of triglyceride transport rates were seen with fructose substitution in the 85% carbohydrate diets using both the heparin infusion lipolytic rate method and the 3H-glycerol methods of assessment of tryglyceride turnover (- 16 and - 21%, respectively). Dietary fructose induced no significant changes in either basal levels or responses during a "formula tolerance test" of glucose, insulin, or glucagon. Thus, dietary fructose given for several weeks does not appear to cause further elevations of plasma triglyceride levels in hypertriglyceridemic men.

Relationships among nutritional status, disease progression, and survival in HIV infection.

This investigation retrospectively studied relationships between survival in human immunodeficiency virus-seropositive outpatients receiving recent therapies (n = 77) and two markers of nutritional status, serum albumin and percent of usual body weight. Subjects were observed for an average of 186 +/- 8 days; 19% died within the study period. Kaplan-Meier curves and Cox regressions showed that older subjects who had lower CD4 counts, lower albumin levels, or had lost more weight demonstrated poorer survival. Albumin levels and weight loss were related to CD4 counts. The relative risk of death for subjects with low albumin levels (< 3.5 g/dl) was 3.6 times greater (p < 0.021, with 95% confidence limits [95%CL] of 1.2-10.9) than that for subjects with normal albumin levels (> or = 3.5 g/dl), even after controlling for age and CD4 counts. Similarly, after controlling for CD4 counts and age, subjects whose baseline body weights were < 90% of their usual weight had a greater relative death risk (8.3 times greater, p < 0.002, 95% CL 2.3-34.1) than those who had lost less. Survivors and nonsurvivors who had similar CD4 counts differed significantly in albumin levels (p < 0.05). Thus, nutritional status influences survival independent of CD4 counts.

Potential histamine H2-receptor antagonists. 4. Benzylhistamines.

As part of our studies aimed at designing histamine H2-receptor antagonists, the effect on histaminergic activity of introducing benzyl substituents at various positions in the histamine molecule is described. New synthetic methods are reported for the novel 4-benzyl-, beta-benzyl- and 4,N tau-dibenylhistamines and the reported 2-benzylhistamine. The novel N tau-benzylhistamine was synthesized by the versatile route reported by us for the synthesis of N tau-methylhistamine. These benzylhistamines, together with the reported N alpha- and N pi-benzylhistamines, were tested for agonist and antagonist activity at both H1 and H2 receptors. The results obtained indicate that introduction of a benzyl group into the histamine molecule causes a marked reduction in H1- or H2-agonist activity, and none of the compounds showed consistent antagonist activity. Evidently, the sterically demanding benzyl substituent is not easily accommodated in the agonist binding mode and is unable to locate a lipophilic receptor region for potential hydrophobic binding.

Cross-clade immune responses after immunization with a whole-killed gp120-depleted human immunodeficiency virus type-1 immunogen in incomplete Freund's adjuvant (HIV-1 immunogen, REMUNE) in human immunodeficiency virus type-1 seropositive subjects.

Lymphocyte proliferation responses to gp120-depleted HZ321 virus (clade A) antigen were compared to BAL human immunodeficiency virus (HIV) virus antigen (clade B) responses, clade E HIV virus antigen responses, and purified native p24 antigen responses in 15 human immunodeficiency virus type-1 (HIV-1) seropositive subjects immunized with a whole-killed inactivated gp120-depleted HIV-1 antigen in Incomplete Freund's adjuvant (HIV-1 immunogen, REMUNE). A significant increase in lymphocyte proliferation to HZ321 antigen was observed after immunization with the HIV-1 immunogen (p = 0.02). A strong association was demonstrated between the HIV-1 immunizing antigen, HZ321, and native p24 antigen responses (r = 0.80, p < 0.0001). Furthermore, a strong association in terms of proliferative responses was demonstrated between HZ321 virus (clade A) responses and BAL virus (clade B) (r = 0.95, p < 0.0001) and clade E virus antigen (r = 0.92, p < 0.0001). Proliferative responses to HIV antigens also correlated with baseline CD4 counts. Taken together, these results support the specificity of immune responses induced by REMUNE (HIV-1 immunogen). The development of cross-reactive immune responses between clades and to the more conserved epitopes of the virus have implications in the development of therapeutic and prophylactic HIV vaccines.

Association of hydrophobic substances with hemin. Characterization of the reverse type I binding spectrum and its relationship to cytochrome P-450.

When hydrophobic compounds were added to a solution of protoferriheme, a a reverse type I spectral change was produced when observed by difference spectroscopy. The spectrum had a peak at 422 nm and a trough at 387 nm, and the characteristics were dependent on the pH of the sample. An association constant for the complex could be determined and was also found to be pH sensitive, with the association constant dropping to zero at values below pH 7.0 and above pH 8.5. The determination of the delta Absmax for the ethylbenzene-hemin complex at various hemin concentrations indicates monomeric heme to be the species responsible for binding the hydrocarbon with the concomitant generation of the reverse type I spectral change.

Long-term central venous catheters in patients with acquired immunodeficiency syndrome.

BACKGROUND: As long-term vascular access becomes more prevalent among patients with AIDS, it is becoming more important to consider their potential complications. METHODS: One hundred two central venous access devices placed in 84 patients with AIDS were reviewed for septic and mechanical complications. Catheters were inserted by one surgeon by means of the cephalic vein cutdown technique. The sample included 88 implanted venous reservoir catheters (86.3%) and 14 tunneled central venous catheters (13.7%). RESULTS: Mean catheter life was 141 +/- 15 days. Total number of catheter days was 14,383. The catheter-related infection rate was 0.125 episodes/100 catheter-days. Staphylococcus aureus was the most commonly isolated pathogen in the sample. Mechanical complications were rare (0.05 episodes/100 catheter-days). CONCLUSION: When these data are compared with other, smaller series in the literature, the findings suggest that long-term central venous catheters inserted in patients with AIDS are safe and effective for the multiple infusion therapies required in these patients.

Comparison of meclofenamate sodium with codeine and placebo for the treatment of episiotomy pain.

Meclofenamate sodium, a nonsteroidal anti-inflammatory drug with proven analgesic effects, was compared at two dose levels (200 mg and 100 mg) with codeine (60 mg) and placebo in a double-blind, randomized study of 327 women experiencing episiotomy pain after normal delivery. Meclofenamate sodium at either dose was significantly better than codeine or placebo in reducing pain intensity and increasing pain relief, and it had a longer duration of action. Adverse effects were minimal, and their frequency did not differ significantly among treatment groups. Meclofenamate sodium appears to be as safe as and more effective than codeine for the management of episiotomy pain.

Double-blind comparison of meclofenamate sodium with codeine and placebo for the pain of episiotomy.

Meclofenamate sodium, a nonsteroidal anti-inflammatory agent, was compared at two dose levels (100 mg and 200 mg) with codeine (60 mg) and placebo in a double-blind, randomized study of 218 women after normal vaginal delivery. The purpose was to determine the analgesic efficacy and safety of meclofenamate sodium for the short-term treatment of acute episiotomy pain. Meclofenamate sodium was significantly better than placebo in most measures of pain relief and reduction of pain intensity. The 100-mg dose of meclofenamate sodium was significantly better than codeine in relieving pain. Adverse experiences with the study medications were minimal (6.4%). Patients receiving codeine reported more side effects than did those receiving either dose of meclofenamate sodium. Meclofenamate sodium is a safe, effective analgesic for acute episiotomy pain.

Comparison of meclofenamate sodium with buffered aspirin and placebo for the relief of postoperative dental pain.

The analgesic effect of meclofenamate sodium at two dose levels (100 mg and 200 mg) was compared with the effects of buffered aspirin (600 mg) and placebo in a double-blind, randomized study of 105 dental outpatients with acute pain following third-molar extraction. Meclofenamate sodium at either dose level was significantly superior to both buffered aspirin and placebo, resulting in significantly greater relief of pain. All four treatments were well tolerated, and side effects were minimal. Meclofenamate sodium is a safe, highly effective analgesic for the relief of acute pain.

Analgesic efficacy of meclofenamate sodium in episiotomy pain.

Meclofenamate sodium was compared, double-blind, with codeine and placebo for the treatment of acute episiotomy pain. One hundred sixty-eight women with moderate or severe episiotomy pain after normal delivery were assigned randomly to one of four treatment groups: one received meclofenamate sodium 200 mg at dose 1 and 100 mg at doses 2 and 3; one received meclofenamate sodium 100 mg at dose 1 and 50 mg at doses 2 and 3; one received codeine 60 mg at all three doses; and one received placebo at all three doses. Efficacy measurements were evaluated periodically for 6 hours after medication. After the first administration, both doses of meclofenamate sodium were significantly superior to placebo and to codeine from 2-6 hours in pain intensity difference and pain relief. For second and third doses, data were available for too few patients to allow valid analysis and interpretation. Adverse effects occurred in 4 patients in each meclofenamate sodium group, and in 8 in the codeine group and in 6 in the placebo group. The study indicates that single 100- and 200-mg doses of meclofenamate sodium are as safe as, and significantly more effective than, codeine 60 mg or placebo for episiotomy pain.

Ewing's tumor metastatic to the clivus, simulating meningitis: case report.

Ewing's sarcoma, which is regarded as one of the most lethal primary bone tumors, lies in the domain of the orthopedic surgeon because it occurs most commonly in the shaft of the long bones, especially in the lower extremities. Pain, leukocytosis, fever, anemia, and an elevated erythrocyte sedimentation rate are commonly seen. We are presenting a case of Ewing's sarcoma of the left greater trochanter with metastasis to the clivus producing a bilateral 6th nerve palsy. The presence of fever, nuchal rigidity, and photophobia simulated meningitis. The rapid evolution of radiological signs will be discussed.

Pharmacology, pharmacokinetics, and therapeutic use of meclofenamate sodium.

Meclofenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) approved for use in arthritis (osteo and rheumatoid), analgesia (mild to moderate pain), dysmenorrhea, and heavy menstrual blood loss (menorrhagia). At least three different biochemical effects have been defined for meclofenamic acid. It is a potent inhibitor of the enzyme cyclooxygenase, thereby inhibiting the production of prostaglandins. It also inhibits the release of 5-HETE and LTB4 from human neutrophils stimulated with calcium ionophore and antagonizes the response of tissues to certain prostaglandins. These mechanisms may explain in part the pharmacological profile and clinical effectiveness of this compound. The rapid onset of activity of meclofenamic acid and its duration of action may be the result of its pharmacokinetic profile. Sodium meclofenamate is completely bioavailable from capsules relative to an oral suspension dosage form. Maximum meclofenamic acid plasma concentrations are achieved in 0.5-2 h following doses of capsules. Meclofenamic acid is extensively metabolized. One of the metabolites, metabolite 1, is approximately 20% as active as the parent compound in inhibiting cyclooxygenase activity in vitro. This metabolite accumulates in plasma during repeated dosing. It is possible that this metabolite may contribute to at least some of the activity observed following administration of sodium meclofenamate.

Characterisation of a type 2 bovine viral diarrhoea virus isolated from cattle in the UK.

Two genotypes of bovine viral diarrhoea virus (BVDV) are recognised. Type 2 was first recognised when virulent strains caused significant losses among cattle in North America. Subsequently, BVDV type 2 has been found in many other countries, but recent studies have shown that only type 1 BVDV is circulating in the UK herds (sheep and cattle) with type 1a predominating. During routine genotyping of UK BVDV isolates, a type 2 isolate was identified. Phylogenetic analysis of the 5'-untranslated region of the viral genome showed it to be a BVDV type 2a, most similar to a low virulent US strain of BVDV type 2. Antigenic typing with a panel of monoclonal antibodies verified this classification. This is the first confirmed isolation of BVDV type 2 found circulating in the UK.