Asymmetries in core-collapse supernovae from maps of radioactive 44Ti in Cassiopeia A.

Asymmetry is required by most numerical simulations of stellar core-collapse explosions, but the form it takes differs significantly among models. The spatial distribution of radioactive (44)Ti, synthesized in an exploding star near the boundary between material falling back onto the collapsing core and that ejected into the surrounding medium, directly probes the explosion asymmetries. Cassiopeia A is a young, nearby, core-collapse remnant from which (44)Ti emission has previously been detected but not imaged. Asymmetries in the explosion have been indirectly inferred from a high ratio of observed (44)Ti emission to estimated (56)Ni emission, from optical light echoes, and from jet-like features seen in the X-ray and optical ejecta. Here we report spatial maps and spectral properties of the (44)Ti in Cassiopeia A. This may explain the unexpected lack of correlation between the (44)Ti and iron X-ray emission, the latter being visible only in shock-heated material. The observed spatial distribution rules out symmetric explosions even with a high level of convective mixing, as well as highly asymmetric bipolar explosions resulting from a fast-rotating progenitor. Instead, these observations provide strong evidence for the development of low-mode convective instabilities in core-collapse supernovae.

An ultraviolet-optical flare from the tidal disruption of a helium-rich stellar core.

The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies. Previous candidate flares have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two 'relativistic' candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet. Here we report a luminous ultraviolet-optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decay of the light curve follow the predicted mass accretion rate and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about two million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.

Effects of electroconvulsive therapy on amygdala function in major depression - a longitudinal functional magnetic resonance imaging study.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, little is known regarding brain functional processes mediating ECT effects. METHOD: In a non-randomized prospective study, functional magnetic resonance imaging data during the automatic processing of subliminally presented emotional faces were obtained twice, about 6 weeks apart, in patients with major depressive disorder (MDD) before and after treatment with ECT (ECT, n = 24). Additionally, a control sample of MDD patients treated solely with pharmacotherapy (MED, n = 23) and a healthy control sample (HC, n = 22) were obtained. RESULTS: Before therapy, both patient groups equally showed elevated amygdala reactivity to sad faces compared with HC. After treatment, a decrease in amygdala activity to negative stimuli was discerned in both patient samples indicating a normalization of amygdala function, suggesting mechanisms potentially unspecific for ECT. Moreover, a decrease in amygdala activity to sad faces was associated with symptomatic improvements in the ECT sample (r spearman = -0.48, p = 0.044), and by tendency also for the MED sample (r spearman = -0.38, p = 0.098). However, we did not find any significant association between pre-treatment amygdala function to emotional stimuli and individual symptom improvement, neither for the ECT sample, nor for the MED sample. CONCLUSIONS: In sum, the present study provides first results regarding functional changes in emotion processing due to ECT treatment using a longitudinal design, thus validating and extending our knowledge gained from previous treatment studies. A limitation was that ECT patients received concurrent medication treatment.

The safety and tolerability of oral AZD5069, a selective CXCR2 antagonist, in patients with moderate-to-severe COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by neutrophil-dominated airway mucosal inflammation and elevated neutrophil counts in sputum and lung tissue. CXC chemokine receptor 2 (CXCR2) is predominantly expressed on neutrophils and mediates the migration of neutrophils to inflammatory sites. AZD5069 is a small molecule CXCR2 antagonist with the potential to inhibit neutrophil migration into the airways in patients with COPD. METHODS: This 4-week, randomized, double-blind, placebo-controlled, parallel-group, multi-center, Phase IIa study evaluated the safety and tolerability of AZD5069 in patients with moderate-to-severe COPD (ClinicalTrials.gov identifier: NCT01233232). The pharmacokinetics and effect of AZD5069 on blood neutrophil counts were also assessed. Patients completed daily diary cards and attended weekly clinic visits for safety assessments. RESULTS: 87 patients (mean FEV1 56% pred; mean age 64 years; 69% male) were randomized to receive placebo (n = 29), AZD5069 50 mg bid (n = 30) or AZD5069 80 mg bid (n = 28) for 4 weeks. AZD5069 was well tolerated with adverse events (AEs) reported in 9 (31%), 10 (33%) and 6 (21%) patients in the placebo, AZD5069 50 mg and AZD5069 80 mg groups, respectively. AEs were generally mild or moderate in severity. The incidence of infections, the most commonly reported AE, was similar across the three groups (17%, 17% and 11% of patients in the placebo, AZD5069 50 and 80 mg groups, respectively). Blood neutrophil counts decreased on average from baseline by 14-40% and 13-36% in the AZD5069 50 mg and 80 mg groups, respectively, and 4 patients discontinued from the study due to decreased neutrophil count, 3 in the AZD5069 50 mg group and 1 in the 80 mg group. The systemic exposure (AUC and Cmax) of AZD5069 increased less than in proportion to the dose and there was a large overlap in the individual exposures between the two dose levels. CONCLUSIONS: AZD5069 was well tolerated overall in those patients who completed study treatment, with no increase in infection rates in either dosage group compared with placebo. Further studies with AZD5069 appear to be warranted.

[Indications and concept of follow-up care of home-monitoring for premature and risk infants]. / Indikation und Nachsorgekonzept zur Heimmonitorüberwachung in der Komplexbetreuung von Früh- und Risikoneugeborenen.

The pros and cons of home monitoring especially for premature infants with continuing apneic episodes and/or chronic lung disease are an ongoing discussion. The controversy spans socio-economic requirements, medical indication as well as patient and family needs. Here, the costs of home monitoring and follow-up care on the one hand and longer hospitalization times on the other need to be considered. This article aims to create a basis for this discussion by summarizing current evidence for the indications and considerations for differential diagnoses while also outlining the established follow-up program for these patients at the Dr. v. Hauner Children's Hospital at the Ludwig-Maximilians-University Munich, Germany.

[Establishment of a Neonatal ECMO Programme on the Basis of a Special Training Programme--A 6-year Analysis]. / Etablierung neonataler ECMO bei Lungenversagen auf der Grundlage eines speziellen Trainingsprogramms--Eine 6-Jahres-Analyse.

BACKGROUND: Internationally the need for neonatal ECMO is decreasing and the Extracorporeal Life Support Organization (ELSO) recommends that centres providing neonatal ECMO should treat at least 6 children per year. METHOD: After a one-year training programme and preparation of the clinical application, neonatal ECMO was established and subsequently 41 infants [median age 1 day (1-172 days), median weight 3.25 kg (1.27-5.79 kg)] with severe respiratory failure have been treated within a 6-year period (fall 2008-fall 2014). For rescue therapy we provide inhaled nitric oxide, high-frequency oscillation and other differentiated ventilator strategies. Parallel to the clinical use of ECMO all employees have been trained in a special programme at 3-monthly intervals. RESULTS: By establishing an elaborate training programme and concentrating the treatment of critically ill newborns in one centre, the expertise of both running and preventing of neonatal ECMO due to pulmonary failure can be achieved. The diagnoses correlate to those of other centres which perform neonatal ECMO. 13 infants needed ECMO. The resulting overall survival rate was 11/12 (91.7%) infants treated with ECMO with a curative approach. All patients could be weaned from ECMO. CONCLUSION: In the context of a specialised university hospital with all treatment options for critically ill newborns and with the establishment of a specialised training programme, neonatal ECMO for pulmonary failure can achieve equally good results in comparison to those of national and international ECMO centres.

Surgical management of intrathoracic wooden skewers migrating from the stomach and duodenum in dogs: 11 cases (2014-2020).

OBJECTIVES: To describe the clinical presentation, management and outcome of cases presenting with intrathoracic wooden skewers originating from the abdominal gastrointestinal tract. MATERIALS AND METHODS: Clinical records of dogs presented and treated for an intrathoracic wooden skewer were reviewed from June to August 2020. Data included signalment, clinical presentation, duration of clinical signs, haematological and biochemical abnormalities, diagnostic imaging findings, surgical procedure, postoperative complications and outcome. RESULTS: Eleven dogs were included in the study. In all cases, the foreign body was identified as a wooden skewer. The most common clinical signs were anorexia/hyporexia (n=7), vomiting/regurgitation (n=7), lethargy (n=6), pyrexia (n=4) and gait abnormalities/lameness (n=3). CT correctly identified a wooden skewer in all cases when performed (n=7). A coeliotomy combined with transdiaphragmatic thoracotomy was performed in six of 11 cases (55%), a coeliotomy combined with median sternotomy in four of 11 cases (36%) and a median sternotomy alone was performed in one case. Foreign bodies penetrated from the stomach (n=10) or the duodenum (n=1). Intrathoracic trauma was most commonly identified to the lungs (n=3) and pericardium (n=3). Complications occurred in three of 11 cases (27%), two minor and one resulting in death. Ten of the 11 cases (91%) survived to discharge. Long-term outcome was available for seven of 11 cases (66%), all of them excellent. CLINICAL SIGNIFICANCE: Despite the challenges of managing wooden skewers penetrating the thoracic cavity from the abdominal gastrointestinal tract, the majority of the patients are stable to undergo diagnostic procedures, surgical exploration and management with low morbidity and excellent short- and long-term prognosis.

Outcome of caudal superficial epigastric axial pattern flaps in dogs and cats: 70 cases (2007-2020).

OBJECTIVES: To describe the outcome and complications associated with the use of caudal superficial epigastric axial pattern flaps in dogs and cats. MATERIAL AND METHODS: Multicentre retrospective review and descriptive study of clinical records of dogs and cats having undergone caudal superficial epigastric axial pattern flaps between 2007 and 2020. Data retrieved included signalment, aetiology of surgical defect, tumour type, presence/absence of clean surgical margins, presence/absence of post-operative wound infection, use of peri- and post-operative antibiotics, duration of anaesthesia, duration of surgery, presence and duration of hypothermia, presence and duration of hypotension, presence/absence of post-operative surgical drain and length of caudal superficial epigastric axial pattern flap. The incidence of complications and outcomes were documented. RESULTS: Seventy cases met the inclusion criteria; 51 dogs and 19 cats. In dogs, 67% of cases developed complications (59% minor, 8% major) and 33% had uneventful wound healing. In cats, 53% of cases developed complications, (47% minor, 5% major) and 47% had uneventful wound healing. In dogs, the percentage of cases experiencing dehiscence, necrosis, seroma, oedema and post-operative infection was 31%, 29%, 26%, 26% and 16% respectively. In cats, this was 26%, 16%, 11%, 0% and 5% respectively. A good overall outcome was seen in 77% of dogs and 79% of cats. A poor overall outcome was seen in 4% of dogs and 0% of cats. CLINICAL SIGNIFICANCE: Caudal superficial epigastric axial pattern flaps are traditionally thought more robust than other flaps, yet complication rates remain high, despite a high overall success rate.

Can concordance between actual care received and a pathway map be measured on a population level in Ontario? A pilot study.

Background: Clinical pathways are associated with improved adherence to clinical guidelines; however, most studies have evaluated pathways for a single intervention at a single institution. The objective of the present study was to develop and evaluate a method of measuring concordance with a population-based clinical pathway map to determine if that method could be feasible for assessing overall health system performance. Methods: Patients with stage ii or iii colon cancer diagnosed in 2010 were identified, and clinical data were obtained through linkages to administrative databases. Pathway concordance was defined a priori based on receipt of key elements of the Ontario Health (Cancer Care Ontario) colorectal pathway maps. For stages ii and iii colon cancer alike, concordance was reported as the proportion of patients receiving care that followed the predefined key elements of the pathway map. Regression analysis was used to identify predictors of concordant care. Results: Our study identified 816 patients with stage ii and 800 patients with stage iii colon cancer. Of the patients with stage ii disease, 70% (n = 571) received concordant care. Of the patients with stage iii disease, results showed high concordance for all key elements except receipt of chemotherapy, leading to an overall concordance rate of 39% for that cohort. Conclusions: Our method of measuring concordance was feasible on a population-based level, but future studies to validate it and to develop more sophisticated methods to measure concordance in larger cohorts and various disease sites are necessary. Measurement of clinical pathway concordance on a population-based level has the potential to be a useful tool for assessing system performance.

3-Hydroxybenzo[a]pyrene in the urine of workers with occupational exposure to polycyclic aromatic hydrocarbons in different industries.

OBJECTIVES: This study was conducted to assess external and internal exposure of workers to polycyclic aromatic hydrocarbons (PAHs). In this context, the analytical and diagnostical reliability of 3-hydroxybenzo[a]pyrene (3OH-BaP) as a biomarker of internal exposure to PAHs was established. METHODS: Ambient and biological monitoring was carried out of 225 PAH-exposed employees of different industries. External exposure was determined by personal air sampling and analysis of 16 EPA-PAH. Internal exposure was examined by the urinary metabolites 3OH-BaP, 1-hydroxypyrene (OH-Pyr) and monohydroxylated phenanthrenes (OH-Phens). RESULTS: Benzo[a]pyrene (BaP) was detected at all workplaces. Concentrations in the breathing zone of the workers ranged from below the limit of detection up to 44.3 mug/m(3). In biological monitoring, urinary 3OH-BaP was found in median concentrations of 0.8 ng/g creatinine (crea) and the 95th percentile of 6.7 ng/g crea. The results ranged from the limit of detection up to 19.5 ng/g crea. Only 1% of the analysed samples showed concentrations below the limit of detection (0.05 ng/l). Regarding median concentrations, workers in coking plants showed lower 3OH-BaP concentrations (0.5 ng/g crea) than those employed in the production of fireproof material in refractories (1.1 ng/g crea), converter infeed (1.2 ng/g crea) and graphite electrode production (1.3 ng/g crea). Strong correlations of 3OH-BaP with OH-Pyr and the sum of OH-Phens were found for the workplaces converter infeed, coking plants and graphite electrode production (r(Pearson) ranging from 0.618 to 0.867, p<0.001). The poor correlation of BaP in the air and 3OH-BaP in urine is most probably caused by routes of uptake other than via air-for example, dermal uptake. CONCLUSION: 3OH-BaP as a metabolite of the carcinogenic BaP could be shown to be a diagnostically specific and sensitive biomarker for determining the internal exposure of workers in different industries. Using this method, the estimation of health risks for workers can be fundamentally improved, because the 3OH-BaP represents the group of carcinogenic PAHs. The procedure for analysing 3OH-BaP is complex, but it is robust and produces reliable results.

TNF receptors 1 and 2 exert distinct region-specific effects on striatal and hippocampal grey matter volumes (VBM) in healthy adults.

Tumour necrosis factor alpha (TNFα) has been implicated in the pathophysiology of neurodegenerative and neuropsychiatric disease, with research highlighting a role for TNFα in hippocampal and striatal regulation. TNFα signals are primarily transduced by TNF receptors 1 and 2 (TNFR1 and TNFR2), encoded by TNFRSF1A and TNFRSF1B, which exert opposing effects on cell survival (TNFR1, neurodegenerative; TNFR2, neuroprotective). We therefore sought to explore the respective roles of TNFR1 and TNFR2 in the regulation of hippocampal and striatal morphology in an imaging genetics study. Voxel-based morphometry was used to analyse the associations between TNFRSF1A (rs4149576 and rs4149577) and TNFRSF1B (rs1061624) genotypes and grey matter structure. The final samples comprised a total of 505 subjects (mean age = 33.29, SD = 11.55 years; 285 females and 220 males) for morphometric analyses of rs1061624 and rs4149576, and 493 subjects for rs4149577 (mean age = 33.20, SD = 11.56 years; 281 females and 212 males). Analyses of TNFRSF1A single nucleotide polymorphisms (SNPs) rs4149576 and rs4149577 showed highly significant genotypic associations with striatal volume but not the hippocampus. Specifically, for rs4149576, G homozygotes were associated with reduced caudate nucleus volumes relative to A homozygotes and heterozygotes, whereas for rs4149577, reduced caudate volumes were observed in C homozygotes relative to T homozygotes and heterozygotes. Analysis of the TNFRSF1B SNP rs1061624 yielded a significant association with hippocampal but not with striatal volume, whereby G homozygotes were associated with increased volumes relative to A homozygotes and heterozygotes. Our findings indicate a role for TNFR1 in regulating striatal but not hippocampal morphology, as well as a complementary role for TNFR2 in hippocampal but not in striatal morphology.

Swift and NuSTAR observations of GW170817: Detection of a blue kilonova.

With the first direct detection of merging black holes in 2015, the era of gravitational wave (GW) astrophysics began. A complete picture of compact object mergers, however, requires the detection of an electromagnetic (EM) counterpart. We report ultraviolet (UV) and x-ray observations by Swift and the Nuclear Spectroscopic Telescope Array of the EM counterpart of the binary neutron star merger GW170817. The bright, rapidly fading UV emission indicates a high mass (≈0.03 solar masses) wind-driven outflow with moderate electron fraction (Ye ≈ 0.27). Combined with the x-ray limits, we favor an observer viewing angle of ≈30° away from the orbital rotation axis, which avoids both obscuration from the heaviest elements in the orbital plane and a direct view of any ultrarelativistic, highly collimated ejecta (a γ-ray burst afterglow).

A novel metastatic animal model reflecting the clinical appearance of human neuroblastoma: growth arrest of orthotopic tumors by natural, cytotoxic human immunoglobulin M antibodies.

Neuroblastoma (NB), the most common extracranial solid tumor in childhood is associated with poor prognosis in patients with advanced tumor stages. Natural human cytotoxic anti-NB IgM antibodies present in the serum of healthy humans are discussed as a potential novel immunotherapeutic regimen against human NB because these antibodies have been shown to affect growth arrest of solid s.c. xenografts of human NB in nude rats. Subcutaneously induced tumors, however, exhibit a different growth pattern compared with the typical growth pattern of NB tumors in humans. Therefore, we developed in this study a novel metastatic tumor model in nude rats that reflects the clinical appearance of human NB and used this model to study the therapeutic efficacy of human anti-NB IgM. Intra-aortal injection of human NB cells in nude rats resulted in the development of large invasive adrenal gland tumors and micrometastases in the liver and bones. Apparently, adrenal glands provide most favorable growth conditions for human NB cells, as documented by the preferential and rapid growth of NB cells in this location. We studied three different treatment protocols of natural human anti-NB IgM. Anti-NB IgM completely inhibited tumor formation and metastases when injected simultaneously with human LAN-1 NB cells (P < 0.05). When antibody treatment was started 6 days after tumor cell injection (i.e., micrometastatic stage), tumor growth was inhibited by 90% (P < 0.05). An anti-NB IgM therapy directed against established tumors (14 days after tumor cell injection) shrank adrenal gland tumors by 90% (P < 0.05). Analysis of the tumors revealed both complement activation and an induction of apoptosis as two independent mechanisms of antitumor function. This study strongly suggests human anti-NB IgM antibodies as new agents for the therapy of neuroblastoma.

The thymus extract Thymex-L potentiates the retinoic acid-induced differentiation of the human myeloid leukemia cell line HL-60.

The human promyelocytic cell line HL-60 can be differentiated with retinoic acid (RA) along the granulocytic pathway. Numerous studies have identified many synergistic combinations of RA with cytostatics, cytokines and other inducers. A combination of RA with the crude thymus extract Thymex-L increased differentiation of HL-60 cells as confirmed by two functional assays and morphology, whereas the extract itself did not show any effect. The functional markers phagocytosis-associated chemiluminescence and nitroblue tetrazolium reduction were more enhanced (up to 4-fold with 1000 micrograms/ml Thymex-L) than morphology. The effect was found over a wide RA concentration range (10(-11) - 10(-6) M) and was dependent on extract concentration. The half-maximal induction of both functional markers was reached at 400 micrograms/ml. To achieve the same effect with the combination in comparison with RA alone, an RA dose reduction of about 100-fold was estimated. The effect was also seen when the cells were pretreated with the thymus extract for two days. The enhancement of RA action by Thymex-L was not correlated with an increase of extracellular or intracellular RA concentration. The active compound in Thymex-L is heat stable and bigger than 5 kDa as confirmed by gelfiltration. The defined thymus peptides thymosin alpha 1, prothymosin alpha 1 and thymopentin were unable to synergistically enhance HL-60 differentiation. These data suggest that the treatment with a thymus extract can increase the sensitivity of HL-60 cells for RA. This may have clinical implications.

Transcription inhibition of SV40 by in vitro DNA methylation.

SV40 DNA was methylated in vitro with prokaryotic or eukaryotic DNA cytosine-5-methyltransferases and the inhibition of transcription by methylation was studied in Xenopus oocytes. Methylation with the prokaryotic HhaI or HpaII methyltransferases did essentially not inhibit transcription of SV40. Methylation with a rat liver methyltransferase led only to minor inhibition of the SV40 early genes, but to a complete shut shut off of the SV40 late genes. Partial methylation showed that methylation of both, the regulatory region and the 5' end of the SV40 late genes, was necessary for the effect on transcription. The TK gene could be inactivated by eukaryotic methylation of either the promoter and the first 50 nucleotides of the gene or the 3' rest of the gene. Insertion of the SV40 enhancer, not containing methylatable CpGs, into the TK upstream region, had no influence on the inhibition of TK gene transcription by methylation.

Supernovae. 44Ti gamma-ray emission lines from SN1987A reveal an asymmetric explosion.

In core-collapse supernovae, titanium-44 ((44)Ti) is produced in the innermost ejecta, in the layer of material directly on top of the newly formed compact object. As such, it provides a direct probe of the supernova engine. Observations of supernova 1987A (SN1987A) have resolved the 67.87- and 78.32-kilo-electron volt emission lines from decay of (44)Ti produced in the supernova explosion. These lines are narrow and redshifted with a Doppler velocity of ~700 kilometers per second, direct evidence of large-scale asymmetry in the explosion.

Expression and modulation of the Lewis x antigen (CD15) on the T cell line Molt-4.

The T cell lines Molt-4 and H9 exhibited a characteristic distribution of the cell adhesion molecule Lewis x (CD15, lacto-N-fucopentanose III) showing an unusually broad peak by flow cytometry ranging from cells without CD15 to cells with high expression. The cytokines IL-1, IL-2, IFN-beta, IFN-gamma, and TNF-alpha, known to activate T cells, did not affect CD15 expression. However, phorbol myristate acetate and the thymic peptide extract Thymex-L were able to enhance both the number of CD15-positive cells and the median fluorescence. The effects of both inducers were dose- and time-dependent. An additive or synergistic effect was not seen. These data suggest that phorbol esters and distinct thymic peptides can modulate the expression of the cell surface antigen CD15.

DNA methylation inhibits transcription by RNA polymerase III of a tRNA gene, but not of a 5S rRNA gene.

Methylation of cytosine in the DNA inhibits the transcription by RNA polymerase II in higher eukaryotes, but has no influence on RNA polymerase I transcription. The effect on RNA polymerase III was unknown, so far. Two polymerase III genes: a type 1 5S rRNA gene and a type 2 tRNA gene were methylated in vitro with a purified eukaryotic DNA methyltransferase (EC2.1.1.37) and their transcription was analyzed in Xenopus oocytes. The 5S rRNA gene, an oocyte 5S rRNA gene from X. laevis which is subject to developmental inactivation, was not affected by methylation. Conversely, transcription of the tRNA gene was 80% inhibited by methylation with the eukaryotic methyltransferase. HhaI and HpaII methylation left its transcription unaffected.

Age dependent kinetic studies of cytoplasmic and lysosomal enzymes of the normal and D-galactosamine injured rat liver.

Rats of two age groups (6 weeks and 30 months) received (1) a single dose of 600 mg D-galactosamine (GalN)/kg body weight by intraperitoneal (i.p.) injection, (2) a single dose of 600 mg GalN/kg body weight i.p. combined with 20 mg prednisolone/kg body weight subcutaneously at the beginning of the experiment. The kinetic studies disclose that GalN produces more severe changes in old than in young animals, represented by the activities of cytoplasmic (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase) and lysosomal (beta-acetylglucosaminidase beta-glucuronidase, cathepsin D) enzymes. Prednisolone diminishes the morphological liver changes as well as the biochemical disturbances in young rats. There is only a protecting effect in morphological changes of old animals within the first 12 h. The prevention of cytoplasmic enzyme activity increase is limited to the first 12 h.

Intensity-modulated tangential beam irradiation of the intact breast.

PURPOSE: To evaluate the potential benefits of intensity modulated tangential beams in the irradiation of the intact breast. METHODS AND MATERIALS: Three-dimensional treatment planning was performed on five left and five right breasts using standard wedged and intensity modulated (IM) tangential beams. Optimal beam parameters were chosen using beams-eye-view display. For the standard plans, the optimal wedge angles were chosen based on dose distributions in the central plane calculated without inhomogeneity corrections, according to our standard protocol. Intensity-modulated plans were generated using an inverse planning algorithm and a standard set of target and critical structure optimization criteria. Plans were compared using multiple dose distributions and dose volume histograms for the planning target volume (PTV), ipsilateral lung, coronary arteries, and contralateral breast. RESULTS: Significant improvements in the doses to critical structures were achieved using intensity modulation. Compared with a standard-wedged plan prescribed to 46 Gy, the dose from the IM plan encompassing 20% of the coronary artery region decreased by 25% (from 36 to 27 Gy) for patients treated to the left breast; the mean dose to the contralateral breast decreased by 42% (from 1.2 to 0.7 Gy); the ipsilateral lung volume receiving more than 46 Gy decreased by 30% (from 10% to 7%); the volume of surrounding soft tissue receiving more than 46 Gy decreased by 31% (from 48% to 33%). Dose homogeneity within the target volume improved greatest in the superior and inferior regions of the breast (approximately 8%), although some decrease in the medial and lateral high-dose regions (approximately 4%) was also observed. CONCLUSION: Intensity modulation with a standard tangential beam arrangement significantly reduces the dose to the coronary arteries, ipsilateral lung, contralateral breast, and surrounding soft tissues. Improvements in dose homogeneity throughout the target volume can also be achieved, particularly in the superior and inferior regions of the breast. It remains to be seen whether the dosimetric improvements achievable with IMRT will lead to significant clinical outcome improvements.