Effects of dexmedetomidine on kidney and brain tissue microcirculation and histology in ovine cardiopulmonary bypass: a randomised controlled trial.

Cardiac surgery requiring cardiopulmonary bypass is associated with postoperative acute kidney injury and neurocognitive disorders, including delirium. Intra-operative inflammation and/or impaired tissue perfusion/oxygenation are thought to be contributors to these outcomes. It has been hypothesised that these problems may be ameliorated by the highly selective α2 -agonist, dexmedetomidine. We tested the effects of dexmedetomidine on renal and cerebral microcirculatory tissue perfusion, oxygenation and histology in a clinically relevant ovine model. Sixteen sheep were studied while conscious, after induction of anaesthesia and during 2 h of cardiopulmonary bypass. Eight sheep were allocated randomly to receive an intravenous infusion of dexmedetomidine (0.4-0.8 µg.kg-1 .h-1 ) from induction of anaesthesia to the end of cardiopulmonary bypass, and eight to receive an equivalent volume of matched placebo (0.9% sodium chloride). Commencement of cardiopulmonary bypass decreased renal medullary tissue oxygenation in the placebo group (mean (95%CI) 5.96 (4.24-7.23) to 1.56 (0.84-2.09) kPa, p = 0.001), with similar hypoxic levels observed in the dexmedetomidine group (6.33 (5.33-7.07) to 1.51 (0.33-2.39) kPa, p = 0.002). While no differences in kidney function (i.e. reduced creatinine clearance) were evident, a greater incidence of histological renal tubular injury was observed in sheep receiving dexmedetomidine (7/8 sheep) compared with placebo (2/8 sheep), p = 0.041. Graded on a semi-quantitative scale (0-3), median (IQR [range]) severity of histological renal tubular injury was higher in the dexmedetomidine group compared with placebo (1.5 (1-2 [0-3]) vs. 0 (0-0.3 [0-1]) respectively, p = 0.013). There was no difference in cerebral tissue microglial activation (neuroinflammation) between the groups. Dexmedetomidine did not reduce renal medullary hypoxia or cerebral neuroinflammation in sheep undergoing cardiopulmonary bypass.

In-depth plasma-wave heating of dense plasma irradiated by short laser pulses.

We investigate the mechanism by which relativistic electron bunches created at the surface of a target irradiated by a very short and intense laser pulse transfer energy to the deeper parts of the target. In existing theories, the dominant heating mechanism is that of resistive heating by the neutralizing return current. In addition to this, we find that large amplitude plasma waves are induced in the plasma in the wake of relativistic electron bunches. The subsequent collisional damping of these waves represents a source of heating that can exceed the resistive heating rate. As a result, solid targets heat significantly faster than has been previously considered. A new hybrid model, capable of reproducing these results, is described.

Symmetry of spherically converging shock waves through reflection, relating to the shock ignition fusion energy scheme.

We examine the properties of perturbed spherically imploding shock waves in an ideal fluid through the collapse, bounce, and development into an outgoing shock wave. We find broad conservation of the size and shape of ingoing and outgoing perturbations when viewed at the same radius. The outgoing shock recovers the velocity of the unperturbed shock outside the strongly distorted core. The results are presented in the context of the robustness of the shock ignition approach to inertial fusion energy.

Exotic dense-matter states pumped by a relativistic laser plasma in the radiation-dominated regime.

In high-spectral resolution experiments with the petawatt Vulcan laser, strong x-ray radiation of KK hollow atoms (atoms without n = 1 electrons) from thin Al foils was observed at pulse intensities of 3 × 10(20) W/cm(2). The observations of spectra from these exotic states of matter are supported by detailed kinetics calculations, and are consistent with a picture in which an intense polychromatic x-ray field, formed from Thomson scattering and bremsstrahlung in the electrostatic fields at the target surface, drives the KK hollow atom production. We estimate that this x-ray field has an intensity of >5 × 10(18) W/cm(2) and is in the 3 keV range.

First Report of Spot Form Net Blotch Caused by Pyrenophora teres f. maculata on Barley in the Mon-Dak Area of the United States.

Pyrenophora teres Drechs. causes net blotch of barley, a common foliar disease in cultivation zones around the world. The disease occurs in two forms, namely a net form net blotch (NFNB) caused by P. teres f. teres and a spot form net blotch (SFNB) caused by P. teres f. maculata. As in other parts of the northern Great Plains, in the Mon-Dak area (western North Dakota and eastern Montana), NFNB is prevalent. SFNB was first reported in western Montana in 1983 (1) and more recently in eastern North Dakota in 2010 (3) but not in the Mon-Dak area. In the summer of 2011, unusual spot lesions that were surrounded by necrosis or chlorosis were observed on different barley cultivars in fields at Williston, ND, Nesson Valley, ND, and Sidney, MT areas. Diseased leaves from various barley cvs. from the three locations were transferred to water agar and incubated at room temperature for 24 h to induce sporulation. Morphological examination of conidia (45 to 169 × 15 to 21 µm) did not show significant differences from a known isolate of P. teres f. teres 0-1 (provided by Tim Friesen, ARS, Fargo, ND). For pathogenicity testing, six 14-day-old plants of barley cv. Tradition were sprayed until runoff with a 2,000 spore/ml suspension of two isolates from each location and the control P. teres f. maculata isolate DEN2.6 (provided by Tim Friesen). Plants were incubated first in a lighted humidity chamber for 24 h and then in a greenhouse for 7 days at 21°C. Regardless of inoculum source, spot lesions surrounded by necrosis or chlorosis, typical of SFNB, appeared on the inoculated leaves within 7 days. Fungi isolated from symptomatic leaves were identified as P. teres and the morphology of the conidia was undistinguishable from those of P. teres f. teres. All control plants which were sprayed with sterile distilled water were symptomless. The pathogenicity test was repeated. Rapid PCR detection and amplicon sequencing (2) of the internal transcribed spacer (ITS) region of ribosomal genes was performed on field and pathogenicity test leaf lesion samples to confirm the presence of P. teres f. maculata. DNA templates were prepared using the Extract-N-Amp Plant PCR Kits (Sigma Chemical Co., St. Louis, MO) and subjected to PCR using ITS1 and ITS4 primers. Amplicons were then purified and sequenced. The 585-bp nucleotide sequences of P. teres f. maculata from Mon-Dak area were submitted to GenBank under accession nos. PtmNES1 (JX187587), PtmSDY1 (JX187588), PtmSDY2 (JX187589), and PtmWIL1 (JX187590). The sequences from the four locations shared 100% similarity and also with P. teres f. maculata (EF452471) from GenBank while showing 10 nucleotide differences (99% similarity) with P. teres f. teres (EF452472).The results represent first report of SFNB in the Mon-Dak. Barley is one of the most important crops in the area. Resistance of the NFNB and SFNB of barley are controlled by different genes (4). Based on this report, SFNB therefore have to be considered in selection of barley cultivars for cultivation in the area. References: (1) H. E Bockelman et al. Plant Dis. 67:696, 1983. (2) R. T. Lartey et al. J. Sugar Beet Res. 40:1, 2003. (3) Z. H. Liu and T. L. Friesen. Plant Dis. 94:480, 2010. (4) O. M. Manninen et al. Genome. 46:1564, 2006.

Evidence that renal arginine transport is impaired in spontaneously hypertensive rats.

Low renal nitric oxide (NO) bioavailability contributes to the development and maintenance of chronic hypertension. We investigated whether impaired l-arginine transport contributes to low renal NO bioavailability in hypertension. Responses of renal medullary perfusion and NO concentration to renal arterial infusions of the l-arginine transport inhibitor l-lysine (10 µmol·kg(-1)·min(-1); 30 min) and subsequent superimposition of l-arginine (100 µmol·kg(-1)·min(-1); 30 min), the NO synthase inhibitor N(G)-nitro-l-arginine (2.4 mg/kg; iv bolus), and the NO donor sodium nitroprusside (0.24 µg·kg(-1)·min(-1)) were examined in Sprague-Dawley rats (SD) and spontaneously hypertensive rats (SHR). Renal medullary perfusion and NO concentration were measured by laser-Doppler flowmetry and polarographically, respectively, 5.5 mm below the kidney surface. Renal medullary NO concentration was less in SHR (53 ± 3 nM) compared with SD rats (108 ± 12 nM; P = 0.004). l-Lysine tended to reduce medullary perfusion (-15 ± 7%; P = 0.07) and reduced medullary NO concentration (-9 ± 3%; P = 0.03) while subsequent superimposition of l-arginine reversed these effects of l-lysine in SD rats. In SHR, l-lysine and subsequent superimposition of l-arginine did not significantly alter medullary perfusion or NO concentration. Collectively, these data suggest that renal l-arginine transport is impaired in SHR. Renal l-[(3)H]arginine transport was less in SHR compared with SD rats (P = 0.01). Accordingly, we conclude that impaired arginine transport contributes to low renal NO bioavailability observed in the SHR kidney.

Fast advection of magnetic fields by hot electrons.

Experiments where a laser-generated proton beam is used to probe the megagauss strength self-generated magnetic fields from a nanosecond laser interaction with an aluminum target are presented. At intensities of 10(15) W cm(-2) and under conditions of significant fast electron production and strong heat fluxes, the electron mean-free-path is long compared with the temperature gradient scale length and hence nonlocal transport is important for the dynamics of the magnetic field in the plasma. The hot electron flux transports self-generated magnetic fields away from the focal region through the Nernst effect [A. Nishiguchi, Phys. Rev. Lett. 53, 262 (1984)] at significantly higher velocities than the fluid velocity. Two-dimensional implicit Vlasov-Fokker-Planck modeling shows that the Nernst effect allows advection and self-generation transports magnetic fields at significantly faster than the ion fluid velocity, v(N)/c(s)≈10.

Direct Polymerase Chain Reaction-Based Detection of Cercospora beticola in Field Soils.

Cercospora beticola, the causal agent of Cercospora leaf spot of sugar beet, survives as pseudostromata in infected sugar beet residues in the soil. Under optimal conditions, overwintering propagules germinate and produce conidia that are dispersed as primary inoculum to initiate infection in sugar beet. We developed a polymerase chain reaction (PCR) technique for rapid detection of C. beticola in field soils. Total DNA was first isolated from soil amended with C. beticola culture using the PowerSoil DNA Kit. The purified DNA was subjected to PCR in Extract-N-Amp PCR mix with CBACTIN primers over 35 cycles. The amplified products were resolved and compared by electrophoresis in 1% agarose gels. The PCR fragment size of C. beticola from the amended field soil correlated in size with the amplicon from control C. beticola culture DNA extract. Additionally, sample soils were collected from sugar beet fields near Sidney, MT and Foxholm, ND. Total DNA was extracted from the samples and subjected to PCR and resolved as previously described. The amplicons were purified from the gels and subjected to BigDye Terminator Cycle sequencing. All sequences from field soils samples, C. beticola-amended field soil, and pure culture were compared by alignment with a C. beticola actin gene sequence from GenBank. The result of the alignment confirmed the amplicons as products from C. beticola. Rapid screening for the presence of C. beticola in the soil by PCR will improve research capabilities in biological control, disease forecasting, and management of this very important sugar beet pathogen.

Generation of ultrahigh-velocity ionizing shocks with petawatt-class laser pulses.

Ultrahigh-velocity shock waves (approximately 10,000 km/s or 0.03c) are generated by focusing a 350-TW laser pulse into low-density helium gas. The collisionless ultrahigh-Mach-number electrostatic shock propagates from the plasma into the surrounding gas, ionizing gas as it becomes collisional. The shock undergoes a corrugation instability due to propagation of the ionizing shock within the gas (the Dyakov-Kontorovich instability). This system may be relevant to the study of very high-Mach-number ionizing shocks in astrophysical situations.

Transient hypertension and sustained tachycardia in mice housed individually in metabolism cages.

The novel environment of a metabolic cage can be stressful for rodents, but few studies have attempted to quantify this stress-response. Therefore, we determined the effects on mean arterial pressure (MAP) and heart rate (HR), of placing mice of both sexes in metabolism cages for 2 days. After surgical implantation of a carotid artery catheter mice recovered individually in standard cages for 5 days. Mice then spent 2 days in metabolism cages. MAP and HR were monitored in the standard cage on Day 5 and in metabolism cages on Days 6-7. MAP increased by 18+/-3 and 22+/-4 %, while HR increased by 27+/-4 and 27+/-6 %, in males and females, respectively, during the first hours after cage switch. MAP decreased to baseline in the fourth and eighth h following metabolism cage switch in males and females, respectively. However, HR remained significantly elevated in both sexes during the entire two-day period in metabolism cages. Females had lower MAP than males both pre- and post-metabolism cage switch, but there were no sex differences in HR. These results demonstrate sustained changes in cardiovascular function when mice are housed in metabolism cages, which could potentially affect renal function.

Renal hypoxia in kidney disease: Cause or consequence?

Tissue hypoxia has been proposed as an important factor in the pathophysiology of both chronic kidney disease (CKD) and acute kidney injury (AKI), initiating and propagating a vicious cycle of tubular injury, vascular rarefaction, and fibrosis and thus exacerbation of hypoxia. Here, we critically evaluate this proposition by systematically reviewing the literature relevant to the following six questions: (i) Is kidney disease always associated with tissue hypoxia? (ii) Does tissue hypoxia drive signalling cascades that lead to tissue damage and dysfunction? (iii) Does tissue hypoxia per se lead to kidney disease? (iv) Does tissue hypoxia precede pathology? (v) Does tissue hypoxia colocalize with pathology? (vi) Does prevention of tissue hypoxia prevent kidney disease? We conclude that tissue hypoxia is a common feature of both AKI and CKD. Furthermore, at least under in vitro conditions, renal tissue hypoxia drives signalling cascades that lead to tissue damage and dysfunction. Tissue hypoxia itself can lead to renal pathology, independent of other known risk factors for kidney disease. There is also some evidence that tissue hypoxia precedes renal pathology, at least in some forms of kidney disease. However, we have made relatively little progress in determining the spatial relationships between tissue hypoxia and pathological processes (i.e. colocalization) or whether therapies targeted to reduce tissue hypoxia can prevent or delay the progression of renal disease. Thus, the hypothesis that tissue hypoxia is a "common pathway" to both AKI and CKD still remains to be adequately tested.

Renal haemodynamics and oxygenation during and after cardiac surgery and cardiopulmonary bypass.

Acute kidney injury (AKI) is a common complication following cardiac surgery performed on cardiopulmonary bypass (CPB) and has important implications for prognosis. The aetiology of cardiac surgery-associated AKI is complex, but renal hypoxia, particularly in the medulla, is thought to play at least some role. There is strong evidence from studies in experimental animals, clinical observations and computational models that medullary ischaemia and hypoxia occur during CPB. There are no validated methods to monitor or improve renal oxygenation during CPB, and thus possibly decrease the risk of AKI. Attempts to reduce the incidence of AKI by early transfusion to ameliorate intra-operative anaemia, refinement of protocols for cooling and rewarming on bypass, optimization of pump flow and arterial pressure, or the use of pulsatile flow, have not been successful to date. This may in part reflect the complexity of renal oxygenation, which may limit the effectiveness of individual interventions. We propose a multi-disciplinary pathway for translation comprising three components. Firstly, large-animal models of CPB to continuously monitor both whole kidney and regional kidney perfusion and oxygenation. Secondly, computational models to obtain information that can be used to interpret the data and develop rational interventions. Thirdly, clinically feasible non-invasive methods to continuously monitor renal oxygenation in the operating theatre and to identify patients at risk of AKI. In this review, we outline the recent progress on each of these fronts.

Active manipulation of the spatial energy distribution of laser-accelerated proton beams.

The spatial energy distributions of beams of protons accelerated by ultrahigh intensity (>10(19)Wcm2) picosecond laser pulse interactions with thin foil targets are investigated. Using separate, low intensity (<10(13)Wcm2) nanosecond laser pulses, focused onto the front surface of the target foil prior to the arrival of the high intensity pulse, it is demonstrated that the proton beam profile can be actively manipulated. In particular, results obtained with an annular intensity distribution at the focus of the low intensity beam are presented, showing smooth proton beams with a sharp circular boundary at all energies, which represents a significant improvement in the beam quality compared to irradiation with the picosecond beam alone.

Normotension, hypertension and body fluid regulation: brain and kidney.

The fraction of hypertensive patients with essential hypertension (EH) is decreasing as the knowledge of mechanisms of secondary hypertension increases, but in most new cases of hypertension the pathophysiology remains unknown. Separate neurocentric and renocentric concepts of aetiology have prevailed without much interaction. In this regard, several questions regarding the relationships between body fluid and blood pressure regulation are pertinent. Are all forms of EH associated with sympathetic overdrive or a shift in the pressure-natriuresis curve? Is body fluid homoeostasis normally driven by the influence of arterial blood pressure directly on the kidney? Does plasma renin activity, driven by renal nerve activity and renal arterial pressure, provide a key to stratification of EH? Our review indicates that (i) a narrow definition of EH is useful; (ii) in EH, indices of cardiovascular sympathetic activity are elevated in about 50% of cases; (iii) in EH as in normal conditions, mediators other than arterial blood pressure are the major determinants of renal sodium excretion; (iv) chronic hypertension is always associated with a shift in the pressure-natriuresis curve, but this may be an epiphenomenon; (v) plasma renin levels are useful in the analysis of EH only after metabolic standardization and then determination of the renin function line (plasma renin as a function of sodium intake); and (vi) angiotensin II-mediated hypertension is not a model of EH. Recent studies of baroreceptors and renal nerves as well as sodium intake and renin secretion help bridge the gap between the neurocentric and renocentric concepts.

Factors associated with awareness, treatment and control of hypertension in a disadvantaged rural Indian population.

The aim of this study was to identify factors associated with awareness, treatment and control of hypertension in a rural setting in India. Following screening of the population, all individuals with hypertension (blood pressure (BP) ⩾140/90 mm Hg or taking antihypertensive medications) were invited to participate in this study. We measured BP, height, weight, skinfolds, waist and hip circumference, and administered a questionnaire to obtain information regarding socioeconomic and behavioural characteristics. Multivariable logistic regression was used to determine factors associated with awareness, treatment and control of hypertension. We recruited 277 individuals with hypertension. Awareness (43%), treatment (33%) and control (27%) of hypertension were poor. Greater distance to health services (odds ratio (OR) 0.56 (95% confidence interval (CI)) 0.32-0.98) was associated with poor awareness of hypertension while having had BP measured within the previous year (OR 4.72, 95% CI 2.71-8.22), older age and greater per cent body fat were associated with better awareness. Factors associated with treatment of hypertension were having had BP measured within the previous year (OR 6.18, 95% CI 3.23-11.82), age ⩾65 years, physical inactivity and greater per cent body fat. The only factor associated with control of hypertension was greater per cent body fat (OR 1.05, 95% CI 1.01-1.11). Improving geographic access and utilisation of health services should improve awareness and treatment of hypertension in this rural population. Further research is necessary to determine drivers of control.

Regional vascular responses to ATP and ATP analogues in the rabbit kidney in vivo: roles for adenosine receptors and prostanoids.

BACKGROUND AND PURPOSE: Our knowledge of the effects of P2-receptor activation on renal vascular tone comes mostly from in vitro models. We aimed to characterise the pharmacology of ATP in the renal circulation in vivo. EXPERIMENTAL APPROACH: In pentobarbitone anaesthetized rabbits, we examined total renal and medullary vascular responses to ATP (0.2 and 0.8 mg kg(-1)), beta, gamma-methylene ATP (beta, gamma-mATP, 7 and 170 microg kg(-1)), alpha, beta-mATP (0.2 and 2 microg kg(-1)) and adenosine (2 and 6 microg kg(-1)) using transit-time ultrasound and laser Doppler flowmetry, respectively. We also determined whether adenosine receptors, NO or prostanoids contribute to the actions of the purinoceptor agonists. KEY RESULTS: Renal arterial boluses of ATP, beta,gamma-mATP, and adenosine produced biphasic changes; ischaemia followed by hyperaemia, in total renal and medullary blood flow. alpha,beta-mATP induced only ischaemia. The adenosine receptor antagonist 8-(p-sulphophenyl)theophylline reduced the responses to adenosine and the hyperaemic responses to ATP and beta,gamma-mATP only. NO synthase inhibition (Nomega-nitro-L-arginine) did not significantly alter responses to the P2 receptor agonists. Subsequent cyclooxygenase inhibition (ibuprofen) reduced the ATP- and beta, gamma-mATP-induced increases in renal blood flow. All other responses remained unchanged. CONCLUSIONS AND IMPLICATIONS: In the rabbit kidney in vivo, alpha, beta-mATP sensitive receptors mediate vasoconstriction. beta,gamma-mATP and ATP induce vasodilation at least partly through adenosine receptors. ATP induced renal vasodilatation is independent of NO and partly dependent on prostanoids in the bulk of the kidney, but not in the vasculature controlling medullary blood flow.

Modification of the sensitivity and repair of potentially lethal damage by diethyldithiocarbamate during and following exposure of plateau-phase cultures of mammalian cells to radiation and cis-diamminedichloroplatinum(II).

Diethyldithiocarbamate (DDC), a chelating agent known to reduce levels of superoxide dismutase and glutathione peroxidase, appears to protect irradiated monolayers of mammalian cells when present for 1 hr before and during irradiation. To examine a possible cause of this modification, the repair of potentially lethal X-ray damage was examined with and without the presence of DDC in the medium overlying the cells postirradiation. Although little repair was seen in full medium alone when DDC was added to the full medium, the amount of repair was comparable to that seen under optimum repair conditions, that is, in Hanks' balanced salt solution. The t 1/2 of the repair process in Hanks' balanced salt solution or in full medium with DDC added was comparable and of the order of 1 to 1.5 hr. The cis-platinum sensitivity of the monolayers is significantly modified by the addition of DDC, and the nature of the modification is dependent upon the time at which the DDC is added to the cells following initiation of cis-platinum exposure. To investigate a possible reason for this protection by DDC, we examined the repair of potentially lethal cis-platinum damage in the cell monolayers. Minimal repair was noted in the presence of either Hanks' balanced salt solution or full medium, but when DDC was added to the full medium, the repair was tripled, and the t 1/2 of the repair process was approximately 2 hr. The ability of DDC to protect cells from exposure to both X-rays and cis-platinum, together with its augmentation of repair of potentially lethal damage following exposure to each, has broad clinical application and is being actively explored in tumor-bearing mice.

Modification of the bone marrow toxicity of cis-diamminedichloroplatinum(II) in mice by diethyldithiocarbamate.

It has been shown that cis-platinum-induced nephrotoxicity in rats can be inhibited by diethyldithiocarbamate (DDC). We report here the bone marrow protective properties of DDC in hybrid (C57BL X BALB/c) mice exposed to single and fractionated doses of cis-platinum. Relatively nontoxic doses of DDC afford maximum protection, using that dose of cis-platinum that would result in the death of 50% of the mice within 9 days as an end point (dose-limiting gut toxicity in mice), when injected 0.5 to 2 hr following i.p. cis-platinum treatment. Survivals of colony-forming units in spleen, nucleated bone marrow cells, and peripheral white blood cell were used to assess the bone marrow protective properties of DDC following both single and fractionated doses of cis-platinum. A dose modification factor of 3.2 (based on colony-forming units in spleen survival) was obtained when DDC (1000 mg/kg) was injected into mice 0.5 hr after graded doses of cis-platinum. When fractionated doses of cis-platinum were used (6 mg/kg on Days 0, 10, 20, and 30), the survival of colony-forming units in spleen was markedly enhanced if the animals were rescued with DDC 0.5 hr following each cis-platinum dose. When bone marrow cellularity was measured immediately before and 2 days after each dose of cis-platinum, a similar pattern of depression and recovery was noted whether DDC was present or not; however, the depression was less marked in mice rescued with DDC. When peripheral white blood cell counts were monitored, the nadir and recovery were similar in the presence or absence of DDC; however, recovery occurred sooner in the animals that had received DDC. Our data support the ability of DDC to modify the bone marrow toxicity of cis-platinum in normal mice. Experiments are in progress in tumor-bearing animals exploring the differential protection afforded by DDC between bone marrow and tumor.

Radiotherapy as initial treatment for bulky stage II testicular seminomas.

Sixteen consecutive patients with bulky stage II seminoma were treated with primary radiotherapy from 1971 to 1982. Bulky stage II seminoma was defined as either Union Internationale Contre le Cancer (UICC) stage IIC (retroperitoneal metastases greater than 5 cm) or IID (palpable retroperitoneal metastases) with no evidence of visceral or supradiaphragmatic disease. The median age was 38 years (range, 26 to 52) and the median size of retroperitoneal disease was 11.5 cm (range, 5 to 25 cm). Patients were treated with generous radiation ports (such as wide hockey-stick or whole abdomen) often followed by boosts to the sites of bulky disease. Median tumor dose was 3,235 cGy (range, 2,700 to 5,668 cGy). Mediastinal (with or without supraclavicular) prophylactic radiation was administered to 15 of the 16 patients with a median dose of 2,590 cGy (range, 1,200 to 3,700 cGy). Treatment toxicity was mild. All 16 patients achieved a complete remission (CR) with radiotherapy. Median follow-up from the time of diagnosis was 60 months, and all patients are currently disease-free. Two patients recurred after therapy but were rendered disease-free with further radiation. These two relapsing patients have remained disease-free, following initial recurrence, for 8 years. The excellent results obtained with modern imaging and radiotherapeutic techniques justify radiotherapy as the initial treatment of choice for bulky stage II seminomas.

Multimodal therapy for the management of localized Ewing's sarcoma of pelvic and sacral bones: a report from the second intergroup study.

A total of 59 eligible patients with localized Ewing's sarcoma of the pelvic and sacral bones were entered into a multimodal Intergroup Ewing's Sarcoma Study (IESS-II) (1978 to 1982) and compared with a historical control series of 68 patients entered into an earlier multimodal Intergroup Ewing's Sarcoma Study (IESS-I) (1973 to 1978). High-dose intermittent multiagent chemotherapy (vincristine, cyclophosphamide, Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH], and dactinomycin) was given to all patients for 6 weeks before and for 70 weeks following local therapy. All patients who had a tumor biopsy or incomplete resection performed received a dose of 55 Gy to the tumor bed. With a median follow-up time of 5.5 years, two of 59 patients (3%) had a local recurrence, five patients (8%) had a local recurrence and metastases, and 17 patients (29%) developed metastases only. There was significant statistical evidence of an advantage in relapse-free survival (RFS) and survival (S) for patients on IESS-II versus IESS-I, P = .006 and P = .002, respectively. At 5 years, the comparison between IESS-II versus IESS-I was 55% versus 23% for RFS and 63% versus 35% for S.