Pulmonary artery angiosarcoma: a clinicopathologic and radiological correlation

A 69-year-old man presented with cough, shortness of breath, and fatigue. He was initially treated for allergies and then for pulmonary embolism. Radiologically, a tumor mass was found to occlude the right pulmonary artery and involve the pulmonary trunk. A right pneumonectomy was performed. Histologically, a cellular malignant spindle and epithelioid tumor with areas of necrosis and brisk mitotic activity was seen. In some areas, the tumor appeared to form vascular channels. Focal osteosarcomatous differentiation was present. Immunohistochemical studies were performed including vimentin, smooth muscle actin, desmin, CD31, CD34, S100, and pan-cytokeratin. The tumor cells were positive for CD31 and vimentin and negative for pan-cytokeratin, CD34, and S100. Two months after surgery, the patient was alive and well.     

Murine epidermal Langerhans cells do not express inducible nitric oxide synthase

In Leishmania-infected macrophages (MΦ), the formation of reactive nitrogen intermediates by the inducible isoform of nitric oxide synthase (iNOS) is critical for the killing of the intracellular parasites. We have recently shown that, in addition to MΦ, epidermal Langerhans cells (LC) can phagocytose Leishmania major, but they do not allow parasite replication. Therefore, we analyzed whether LC and MΦ display the same leishmanicidal effector mechanism. Unlike MΦ, stimulation of unselected epidermal cells with interferon-γ/lipopoly-saccharide did not lead to the release of nitric oxide (NO), and inhibition of NO production had no effect on the rate of infection of LC. iNOS mRNA was clearly detectable in MΦ as well as unselected epidermal cells (the majority of which consists of keratinocytes) after stimulation with different cytokines. In contrast, pure LC obtained by single-cell picking from cytokine-activated or L. major-infected epidermal cells did not express iNOS mRNA. Addition of the NO donor S-nitroso-N-acetylpenicillamine to already-infected LC did not alter their rate of infection, indicating that LC do not utilize exogenous NO for the control of intracellular Leishmania. These results suggest that in the L. major-infected skin, activated MΦ and keratinocytes, but not LC have the ability to express iNOS activity. Therefore, an as yet unidentified, NO-independent mechanism appears to be responsible for the control of parasite replication in LC.     

Prognostic markers in pT3 bladder cancer: A study from the international bladder cancer tissue microarray project

PurposeWe evaluated the prognostic value of 10 putative tumor markers by immunohistochemistry in a large multi-institutional cohort of patients with locally advanced urothelial cancer of the bladder (UCB) with the aim to validate their clinical value and to harmonize protocols for their evaluation.Materials and MethodsPrimary tumor specimens from 576 patients with pathologic (p)T3 UCB were collected from 24 institutions in North America and Europe. Three replicate 0.6-mm core diameter samples were collected for the construction of a tissue microarray (TMA). Immunohistochemistry (IHC) for 10 previously described tumor markers was performed and scored at 3 laboratories independently according to a standardized protocol. Associations between marker positivity and freedom from recurrence (FFR) or overall survival (OS) were analyzed separately for each individual laboratory using Cox regression analysis.ResultsThe overall agreement of the IHC scoring among laboratories was poor. Correlation among the 3 laboratories varied across the 10 markers. There was generally a lack of association between the individual markers and FFR or OS. The number of altered cell cycle regulators (p53, Rb, and p21) was associated with increased risk of cancer recurrence (P < 0.032). There was no clear pattern in the relationship between the percentage of markers altered in an 8-marker panel and FFR or OS.ConclusionsThis large international TMA of locally advanced (pT3) UCB suggests that altered expression of p53, Rb, and p21 is associated with worse outcome. However this study also highlights limitations in the reproducibility of IHC even in the most expert hands.     

An image-based modeling framework for patient-specific computational hemodynamics

We present a modeling framework designed for patient-specific computational hemodynamics to be performed in the context of large-scale studies. The framework takes advantage of the integration of image processing, geometric analysis and mesh generation techniques, with an accent on full automation and high-level interaction. Image segmentation is performed using implicit deformable models taking advantage of a novel approach for selective initialization of vascular branches, as well as of a strategy for the segmentation of small vessels. A robust definition of centerlines provides objective geometric criteria for the automation of surface editing and mesh generation. The framework is available as part of an open-source effort, the Vascular Modeling Toolkit, a first step towards the sharing of tools and data which will be necessary for computational hemodynamics to play a role in evidence-based medicine.     

Postoperative hypofractionated radiotherapy versus conventionally fractionated radiotherapy in malignant gliomas. A preliminary report on a randomized trial

A prospective randomized study of 108 patients with cerebral malignant gliomas was carried out at the Department of Radiation Oncology of Maria Sklodowska-Curie Memorial Center in Kraków. 44 patients with histologically proven glioblastoma multiforme and 64 patients with anaplastic astrocytoma received postoperative radiotherapy. Patients were randomized to two treatment arms: Conventionally Fractionated Radiotherapy (CFR) and Hypofractionated Radiotherapy (HF). In the CFR group, the whole brain was irradiated to the total dose of 50 Gy in 25 fractions over 5 weeks, then a 10 Gy boost in 5 fractions in 5 days was delivered to the site of the primary lesion. In the HF group, there were 3 courses of irradiation separated by a one month interval. In each of the two first series the patients received 20 Gy in 5 fractions in 5 days to the whole brain, and in the third course, 10 Gy boost in 5 days was delivered as in the CFR regimen. The tolerance to treatment has been found to be good in both groups. The 2-year actuarial survival rate for patients with anaplastic astrocytoma was 22% for CFR and 18% for HF. Patients with glioblastoma multiforme treated with HF had a better prognosis in comparison to the CFR group with the two-year actuarial survival rates being 23% and 10%, respectively. This difference is statistically significant at the 0.05 level.     

Analytical Chiral Separation of the Stereoisomers of a Novel Carbonic Anhydrase Inhibitor and Its Deethylated Metabolite,and the Assignment of Absolute Configuration of the Human Metabolite and Chiral Degradation Products

Several approaches to the separation of four stereoisomers, 1–4, of a novel, topically active, carbonic anhydrase inhibitor, 1, with two chiral centers in the molecule and four isomers, 5–8, of its chiral metabolite, 5, were evaluated. These methods include nonchiral derivatization followed by separation on chiral stationary phases (CSPs) and chiral derivatization and separation on nonchiral columns and on CSPs. Baseline separation of stereoisomers 1–4 was achieved in less than 15 min after chiral derivatization with (S)-(+)-l-(l-naphthyl)ethyl isocyanate (NEIC) and chiral chromatography on a (R)-N-(3,5-dinitrobenzoyl)phenyl glycine (DNBPG) column under normal phase (NP) conditions. Similarly, isomers 5-8 were baseline separated in less than 20 min after derivatization with NEIC and chromatography on nonchiral (nitrophenyl) and chiral [(S)-(3,5-dinitrobenzoyl)leucine; DNBL] columns in series under the same NP chromatographic conditions. Only partial separation of the diastereomeric derivatives was observed on a variety of nonchiral columns. In addition, all other direct and indirect chiral separation approaches gave only partial separation of at least two stereoisomers within the group of 1–4 or 5–8. The details of chiral separations using various methods and separation () and capacity factors (k) of the derivatized isomers 1–8 on a series of chiral and nonchiral columns are presented. Using these methods, the absolute configuration of the human metabolite of 1 was established as S ₁ S ₂ (5), and the heat (HD) and light (LD) degradation products of 1 as R ₁ S ₂ (3) and S₁ S ₂ (5), respectively.     

Oligogenic determination of morphine analgesic magnitude: A genetic analysis of selectively bred mouse lines

Two ongoing selective breeding projects have produced mice that display divergent analgesic responses to morphine. These two projects have selected for similar phenotypes: high and low levorphanol analgesia (HAR/LAR lines; Portland, OR) and high and low swim stress-induced analgesia (HA/LA lines; Jastrzebiec, Poland). Evidence suggests genetic commonalities between mice of the two projects. Using a Mendelian breeding protocol, we have recently found that one or two genetic loci predominantly determine the high morphine analgesia exhibited by HA mice. In the present study we demonstrate that the differential morphine analgesia (5 mg/kg. i.p.) displayed by HAR and LAR mice is similarly oligogenic, predominantly determined by two unlinked loci. A complementation analysis, in which the analgesic responses to morphine of the recessive homozygotes of each project (HAR and HA) were compared to those of their hybrid offspring (HAR x HA), revealed that different genetic loci have been fixed in each project. An intriguing bimodal distribution was observed in the HAR x HA population: Some HAR x HA hybrids displayed greater morphine analgesia than either HAR or HA mice, whereas others displayed minimal analgesia. LAR x LA hybrids displayed less analgesia than either LAR or LA mice. The analgesic responses of HAR x LA and LAR x HA mice were comparable to those of their low-line parents. These findings indicate not only that different loci were responsible for producing high morphine responders in each selection project but that these distinct loci can interact synergistically to produce superhigh and superlow responders.     

The effect of accident mechanisms and initial findings on the long-term course of whiplash injury

The aim of this study was to assess the relationships between accident mechanisms as well as initial findings and the long-term course of whiplash injury. A representative sample of 117 consecutive patients referred by primary care physicians was followed-up over 12 months. Fractures or dislocations of the cervical spine, head trauma and pre-existing neurological disorders were exclusion criteria. The interval between the accident and the baseline examination was 7.4 days (SD 4.2 days). Assessment included accident features (e.g. passenger position in the car, head restraint, head position, type of collision), initial symptoms (e.g. intensity and onset of pain, symptoms of neurological dysfunction, multiple symptom score), and signs (restricted neck movement, neurological deficits). At the 1-year examination, patients were divided into an asymptomatic and a symptomatic group and were compared with respect to accident features and baseline findings. Twenty-four percent of patients were still symptomatic after 1 year. Analysing accident mechanisms separately, rotated or inclined head position was the primary feature related to symptom persistence (P=0.005). The symptomatic group scored higher at baseline on the multiple symptom rating (P=0.004) and had a higher incidence of initial headache (P=0.004) and neurological symptoms (P=0.008) together with a higher intensity of headache (P=0.0002) and neck pain (P=0.0009). The following set of initial variables predicted persistence of symptoms at 1 year (logistic regression): intensity of neck pain (P=0.001) and headache (P=0.009), rotated or inclined head position (P=0.02), unpreparedness at the time of impact (P=0.01) and car stationary when hit (P=0.01). In conclusion, accident mechanisms and initial findings suggestive of more severe injury were significantly related to long-term persistence of symptoms after whiplash injury.This study was supported by the Swiss National Science Foundation (project number: 3.883-0.88) and the Swiss Accident Insurance Company (Schweizerische Unfallversicherungsanstalt), Berne     

Body size and food size in freshwater zooplankton

We used double-label liquid scintillation techniques to measure the efficiencies with which eight different-sized zooplankton species ingested four cell types relative to a standard cell type (Chlamydomonas). Efficiency ratios (ERs: clearance rate on cell type X ÷ clearance rate on Chlamydomonas) on the three ultraplankton (<5 μm in diameter) cells (a coccoid bacterium and the algae Synechococcus and Nannochloris) varied greatly among zooplankton species but were not correlated with zooplankton body length. Variation in ERs on a much larger (17 × 14 μm) algal cell (Cryptomonas) was only partly explained by zooplankton body length. The eight zooplankton species were classified into three functional groups: (i) species having moderate to high ERs on all ultraplankton (0.4 < ER < 1.6) and ERs on Cryptomonas proportional to their body lengths (Conochilus, Diaphanosoma, and probably Keratella cochlearis and Ceriodaphnia); (ii) species having extremely low ERs on bacteria (mean ER < 0.05), higher but still low ERs on ultraphytoplankton (ER generally < 0.4), and ERs on Cryptomonas proportional to their body lengths (Bosmina, Diaptomus copepodites and adults); (iii) species having extremely low ERs on all ultraplankton (mean ER < 0.05) and ERs on Cryptomonas much higher than expected given their body lengths (Keratella crassa, Polyarthra, and Diaptomus nauplii). These functional groups follow neither taxonomic nor body-length groupings. We conclude that zooplankton body length may influence the maximal particle size a species can ingest but has little influence on the ingestion of smaller particles. Two frequently used models relating zooplankton body size and food size are unrealistic.     

National policy and situated meaning: the case of Head Start and the handicapped.

Recent amendments to the Economic Opportunity Act required Head Start programs to increase the number of "handicapped" children to ten percent of those served. Using an interactionist perspective and participant observation data from 30 programs, this paper discusses the effect of the legislation on local programs, the process by which official rates of deviance are produced, and the manner in which mandates from the national level alter situated meaning. Implications for theory and policy are suggested.