Positron annihilation signatures associated with the outburst of the microquasar V404 Cygni.

Microquasars are stellar-mass black holes accreting matter from a companion star and ejecting plasma jets at almost the speed of light. They are analogues of quasars that contain supermassive black holes of 10(6) to 10(10) solar masses. Accretion in microquasars varies on much shorter timescales than in quasars and occasionally produces exceptionally bright X-ray flares. How the flares are produced is unclear, as is the mechanism for launching the relativistic jets and their composition. An emission line near 511 kiloelectronvolts has long been sought in the emission spectrum of microquasars as evidence for the expected electron-positron plasma. Transient high-energy spectral features have been reported in two objects, but their positron interpretation remains contentious. Here we report observations of γ-ray emission from the microquasar V404 Cygni during a recent period of strong flaring activity. The emission spectrum around 511 kiloelectronvolts shows clear signatures of variable positron annihilation, which implies a high rate of positron production. This supports the earlier conjecture that microquasars may be the main sources of the electron-positron plasma responsible for the bright diffuse emission of annihilation γ-rays in the bulge region of our Galaxy. Additionally, microquasars could be the origin of the observed megaelectronvolt continuum excess in the inner Galaxy.

Administration of low doses of IL-2 combined to rapamycin promotes allogeneic skin graft survival in mice.

Human CD4(+) CD25(+) FoxP3(+) regulatory T cells (Tregs) prevent allogeneic graft rejection by inhibiting T cell activation, as has been shown in mouse models. Recently, low-dose IL-2 administration was shown to specifically activate Tregs but not pathogenic conventional T cells, leading to resolution of type 1 diabetes in nonobese diabetic mice. We therefore tested the ability of low-dose IL-2 to prevent allogeneic skin graft rejection. We found that while IL-2 alone was inefficient in preventing rejection, combined with rapamycin, IL-2 treatment promoted skin graft survival both in minor disparate and semi-allogeneic skin graft combinations. Tregs are activated by this combined treatment while conventional CD4(+) cell expansion and activation are markedly inhibited. Co-administration of anti-CD25 antibodies dramatically reduces the effect of the IL-2/rapamycin treatment, strongly supporting a central role for Treg activation. Thus, we provide the first preclinical data showing that low-dose IL-2 combined with rapamycin can significantly delay transplant rejection in mice. These findings may form the rational for clinical evaluation of this novel approach for the prevention of transplant rejection.

Surgical repair of aneurysms involving the suprarenal, visceral, and lower thoracic aortic segments: early results and late outcome.

OBJECTIVE: The purpose of this study is to review our experience with surgical repair of lower thoracoabdominal and suprarenal aortic aneurysms to determine early and late survival rates and identify factors influencing morbidity and survival among these patients. MATERIALS: From 1989 through 1998, 165 consecutive patients underwent repair of 108 thoracoabdominal (55 group III and 53 group IV) and 57 suprarenal aneurysms. The study group consisted of 109 men and 56 women with a mean age of 70 years (median, 70 years; range, 29-89 years). Mean aneurysm diameter was 6.9 cm (median, 6.5 cm; range, 4-12 cm). There were 125 aneurysms (76%) repaired electively; 40 repairs (24%) were nonelective. The cause of 12 aneurysms (7%) was chronic aortic dissection; the remaining 153 (93%) were degenerative aneurysms. RESULTS: The early postoperative (30-day) mortality rates were 7% (9/125) for elective and 23% (9/40) for nonelective operations (P =.016). For both elective and urgent procedures, early mortality was 1.8% (1/57) for suprarenal aneurysm repair, 11% (6/53) for group IV thoracoabdominal aneurysms, and 20% (11/55) for group III thoracoabdominal aneurysms (P =.013, suprarenal vs group III). Spinal cord ischemia occurred after 6% (10/165) of aneurysm repairs (4% paraplegia, 2% paraparesis). None of the 57 suprarenal aneurysm repairs were complicated by spinal cord ischemia, whereas it occurred in 2% (1/53) of group IV thoracoabdominal aneurysms and 16% (9/55) of group III thoracoabdominal aneurysms (P =.001, suprarenal vs group III; P =. 016, group IV vs group III). Three (25%) of the 12 patients with dissection developed spinal cord ischemia; this compared with seven (5%) of 153 patients with degenerative aneurysms (P =.027). The cumulative 3-year survival rate for the entire series was 71% (95% CI, 64%-79%), and 5-year survival was 50% (95% CI, 40%-60%). CONCLUSIONS: Aneurysms involving the suprarenal, visceral, and lower thoracic aorta may be repaired with acceptable perioperative mortality and late survival rates. The risk of spinal cord ischemia is increased for patients with aortic dissection and may be stratified according to the proximal extent of the aneurysm.

Carotid endarterectomy in patients less than 50 years old.

PURPOSE: The purpose of this study was to compare the results of carotid endarterectomy (CEA) in a young population with premature atherosclerosis with the results of an older control group, examining perioperative morbidity and mortality data, recurrent stenosis and symptoms, late stroke, and survival data. METHODS: We retrospectively studied 26 patients less than 50 years old (mean, 43.2 +/- 3.8 years) and 30 patients greater than 55 years old (mean, 69.1 +/- 7.4 years) who underwent CEA during the same time period. Data were obtained regarding demographics, atherosclerotic risk factors, indication for CEA, perioperative complications, recurrent stenosis and symptoms, late stroke, and survival. RESULTS: Smoking was more prevalent among young patients who underwent CEA (92% vs 70%; p = 0.036). Young patients were also more likely to be symptomatic at presentation (92% vs 57%; p = 0.003). The perioperative mortality rate (0% vs 0%) and neurologic morbidity rate (0% vs 3%; p = 1.000) were low for the study patients. During a mean follow-up of 67 +/- 42.7 months, there was no significant difference in survival rate (5-year survival rate, 93% vs 81%; p = 0.373), rate of late ipsilateral (4% vs 3%) and contralateral (4% vs 3%) stroke, restenosis and occlusion (26.9% vs 14.3%), recurrent symptoms (22% vs 17%), reoperation (11.5% vs 5.7%), or contralateral disease (17% vs 23%) development that required surgery for the study or the control cohorts. CONCLUSIONS: Our data show that there is a high incidence of smoking and symptomatic presentation among young patients in whom carotid occlusive disease develops. CEA may be performed in young patients with low perioperative morbidity and mortality rates. Recurrent disease, late stroke, and survival rates are not significantly different than for older patients. Follow-up with serial duplex ultrasound and reoperation for symptomatic and high-grade asymptomatic restenosis may decrease the risk of late stroke.

Mesenteric angioplasty in the treatment of chronic intestinal ischemia.

PURPOSE: This study was undertaken to determine the safety and efficacy of percutaneous transluminal angioplasty (PTA) in the treatment of chronic mesenteric ischemia (CMI) in very high-risk surgical patients. METHODS: Twenty-four focal mesenteric stenoses treated from 1984 to 1994 by PTA in 19 patients with CMI were reviewed. All 19 patients were considered poor surgical candidates. Seventeen patients had classic symptoms of CMI, and two patients had atypical abdominal complaints. Vessels dilated included the superior mesenteric artery (18), celiac artery (3), inferior mesenteric artery (1), aorta-superior mesenteric artery vein graft (1), and aorta-splenic artery vein graft (1). Complete follow-up was possible in all patients, with the exception of one patient who had no symptoms when last seen 17 months after the procedure. RESULTS: PTA was technically successful in 18 of 19 patients (95%) and 23 of 24 stenoses (96%). The lone technical failure resulted in superior mesenteric artery dissection with thrombosis and bowel infarction; the patient died despite emergent laparotomy and revascularization (mortality rate, 5%). Complete symptomatic relief was attained in 15 patients (79%), with follow-up showing continued relief of symptoms for a mean of 39 months (range, 4 to 101 months). Partial symptomatic relief was attained in three patients. Recurrent symptoms developed in three patients (20%) at a mean interval of 28 months (range, 9 to 43 months). Repeat PTA performed in two patients provided good technical results and relief from clinical symptoms. One patient had a symptomatic axillary sheath hematoma that required surgical decompression. CONCLUSIONS: Mesenteric PTA is a valuable treatment option in patients who have CMI and are considered very high operative risks. The initial technical success rate is excellent, with the majority of patients having complete symptomatic improvement and continued relief of symptoms at short-term follow-up.

Surface tension properties of human urine: relationship with bile salt concentration.

The surface tension of urine has been simply and rapidly measured using two methods, the DuNouy ring detachment method and the Wilhelmy blade immersion method. The methods agree, the correlation coefficient, r, was 0.992. The effect of ageing of the surface, of storage, of temperature, pH, dilution and albumin on urine surface tension are described. Volume corrected 24 hour urine surface tensions from 6 volunteers over 12 or more days showed variations between individuals of mean surface tensions of 6 mN/m (S.D. +/- 2.16 mN/m). This suggests individual variation in excretion of surface active agents, probably bile salts. This was confirmed by further studies which showed that: 1. Surface tension of urines and rediluted extracts were not significantly different when amphiphilic and hydrophobic solutes including bile salts were extracted from urine and subsequently rediluted in water of the same volume. 2. Bile salt concentration in urine measured by RIA and by enzymatic spectrofluorometric methods correlated well with urine surface tension, r = -0.91, and r = -0.60. 3. Molecular surface area for urinary surfactant was 79 A2 similar to pure conjugated bile salt solutions calculated from dilution studies. We conclude that the main determinant of urine surface tension is bile salt concentration.

The effect of tyrosine conjugation on the critical micellar concentration of free and glycine-conjugated bile salts.

We investigated the effect of conjugation with the aromatic amino acid tyrosine on the critical micellar concentration (CMC) of bile salts. The CMC values were determined by surface tension and by dye solubilization. The surface tension measurement employed the Du Nouy ring detachment method and the dye solubilization measurement utilized a water-insoluble dye, 1-O-tolylazo-2-naphthol. We compared the CMC values of the sodium salts of cholyltyrosine (cholylTyr), deoxycholyltyrosine (deoxycholylTyr), deoxycholylglycyltyrosine (deoxycholylGlyTyr) chenodeoxycholyltyrosine (chenodeoxycholylTyr), chenodeoxycholylglycyltyrosine (chenodeoxycholylGlyTyr), cholyldiglycyltyrosine (cholylGlyGlyTyr) and cholylglycyltyrosine (cholylGlyTyr) with their respective glycine conjugated bile salts. Both techniques of CMC determination indicated that tyrosine conjugation to free and glycine-conjugated bile salts reduced their CMC significantly.

Innervation of the muscle of the bladder in the rat.

A quantitative ultrastructural analysis of the organisation and terminal density of the nerves associated with the muscle of the body of the bladder was undertaken in the rat. The results obtained were suggestive of the organisation of the intramuscular plexuses into 2 separate and possibly functionally distinct networks. The nerves ramifying within the muscle fascicles mostly contained between 1 and 3 axons and on the basis of counts made in 12 animals, appeared to provide the muscle with only a moderate level of innervation. Although adrenergic terminals were frequently seen in the perivascular plexuses, they were rarely encountered in the nerves within the muscle fascicles. The majority of the terminals in the intrafascicular nerves were similar to those normally classified as cholinergic and, in many, the exposed parts of the axonal membrane were closely related to that of adjacent muscle cells. In addition to clear vesicles and large dense-cored vesicles, many of these terminals contained scattered small dense-cored vesicles. It was suggested that the involvement of the material present in the small dense-cored vesicles with acetylcholine in impulse transmission might account for the atypical features of such transmission in the bladder and in particular its resistance to blockade by atropine. The nerves forming the interfascicular networks contained few axons with cholinergic terminals, and were characterised by much larger numbers of a morphologically distinctive type of terminal. Some of these were indistinguishable from those recently defined as the terminals of purinergic axons but their distribution in the nerves suggests that they represent the terminals of afferent axons and is consistent with the concept that, together with those observed in other tissues, such axons are involved in pain perception.