Cutaneous graft-versus-host reaction: prognostic features seen by light microscopy

Acute graft-versus-host disease (GVHD) is a severe complication of bone marrow transplantation. The diagnosis may be made and its course followed by serial skin biopsies. The degree of epidermal change has been used as a guideline in grading each biopsy, but great variation may be found within each grade, especially grade 2 (basal cell vacuolization and dyskeratosis). To find a histologic parameter that is prognostic of more severe acute GVHD, we examined retrospectively the serial biopsies of 54 patients. When we studied early cutaneous graft-versus-host reaction (GVHR), represented by the grade 2 biopsies, the number of dermal and epidermal mononuclear inflammatory cells correlated positively with the probability of developing more severe acute GVHD. In addition, the patients who had more severe acute GVHD tended to have an earlier appearance of cutaneous histologic changes. None of the other histologic parameters examined in these grade 2 biopsies were found to be predictive of GVHD progression. In addition, no histopathologic parameters in these grade 2 biopsies were predictive of the subsequent development of chronic GVHD.     

Embryonal rhabdomyosarcoma of the uterine cervix in a 47-year-old woman

Embryonal rhabdomyosarcoma (RMS) of the female genital tract usually occurs in the vagina during childhood. The uterine cervix as a primary site is rare, but is more frequent until the second decade of life. It usually has a good prognosis and the treatment is based on multidrug chemotherapy, radiotherapy and surgery. RMS accounts for <5% of all adult soft tissue sarcomas. Previous reports that included all primary sites showed a poorer five-year disease specific survival for adults with RMS when compared to the pediatric population. This difference has been attributed to a higher proportion of adverse prognostic clinical and pathological factors, and to inadequate treatment given to adults with RMS. A total of 115 patients with cervical embryonal RMS have previously been described; however, only 10 cases were reported in women older than 40 years. We present a 47-year-old woman treated with radical hysterectomy followed by adjuvant chemotherapy and review the current literature.     

Cardiovascular magnetic resonance for the assessment of patients undergoing transcatheter aortic valve implantation: a pilot study

Background

Before trans-catheter aortic valve implantation (TAVI), assessment of cardiac function and accurate measurement of the aortic root are key to determine the correct size and type of the prosthesis. The aim of this study was to compare cardiovascular magnetic resonance (CMR) and trans-thoracic echocardiography (TTE) for the assessment of aortic valve measurements and left ventricular function in high-risk elderly patients submitted to TAVI.

Methods

Consecutive patients with severe aortic stenosis and contraindications for surgical aortic valve replacement were screened from April 2009 to January 2011 and imaged with TTE and CMR.

Results

Patients who underwent both TTE and CMR (n = 49) had a mean age of 80.8 ± 4.8 years and a mean logistic EuroSCORE of 14.9 ± 9.3%. There was a good correlation between TTE and CMR in terms of annulus size (R² = 0.48, p < 0.001), left ventricular outflow tract (LVOT) diameter (R² = 0.62, p < 0.001) and left ventricular ejection fraction (LVEF) (R² = 0.47, p < 0.001) and a moderate correlation in terms of aortic valve area (AVA) (R² = 0.24, p < 0.001). CMR generally tended to report larger values than TTE for all measurements. The Bland-Altman test indicated that the 95% limits of agreement between TTE and CMR ranged from -5.6 mm to + 1.0 mm for annulus size, from -0.45 mm to + 0.25 mm for LVOT, from -0.45 mm² to + 0.25 mm² for AVA and from -29.2% to 13.2% for LVEF.

Conclusions

In elderly patients candidates to TAVI, CMR represents a viable complement to transthoracic echocardiography.     

Coevolution of tRNA intron motifs and tRNA endonuclease architecture in Archaea

Members of the three kingdoms of life contain tRNA genes with introns. The introns in pre-tRNAs of Bacteria are self-splicing, whereas introns in archaeal and eukaryal pre-tRNAs are removed by splicing endonucleases. We have studied the structures of the endonucleases of Archaea and the architecture of the sites recognized in their pre-tRNA substrates. Three endonuclease structures are known in the Archaea: a homotetramer in some Euryarchaea, a homodimer in other Euryarchaea, and a heterotetramer in the Crenarchaeota. The homotetramer cleaves only the canonical bulge-helix-bulge structure in its substrates. Variants of the substrate structure, termed bulge-helix-loops, appear in the pre-tRNAs of the Crenarcheota and Nanoarcheota. These variant structures can be cleaved only by the homodimer or heterotetramer forms of the endonucleases. Thus, the structures of the endonucleases and their substrates appear to have evolved together.     

Evolution of introns in the archaeal world

The self-splicing group I introns are removed by an autocatalytic mechanism that involves a series of transesterification reactions. They require RNA binding proteins to act as chaperones to correctly fold the RNA into an active intermediate structure in vivo. Pre-tRNA introns in Bacteria and in higher eukaryote plastids are typical examples of self-splicing group I introns. By contrast, two striking features characterize RNA splicing in the archaeal world. First, self-splicing group I introns cannot be found, to this date, in that kingdom. Second, the RNA splicing scenario in Archaea is uniform: All introns, whether in pre-tRNA or elsewhere, are removed by tRNA splicing endonucleases. We suggest that in Archaea, the protein recruited for splicing is the preexisting tRNA splicing endonuclease and that this enzyme, together with the ligase, takes over the task of intron removal in a more efficient fashion than the ribozyme. The extinction of group I introns in Archaea would then be a consequence of recruitment of the tRNA splicing endonuclease. We deal here with comparative genome analysis, focusing specifically on the integration of introns into genes coding for 23S rRNA molecules, and how this newly acquired intron has to be removed to regenerate a functional RNA molecule. We show that all known oligomeric structures of the endonuclease can recognize and cleave a ribosomal intron, even when the endonuclease derives from a strain lacking rRNA introns. The persistence of group I introns in mitochondria and chloroplasts would be explained by the inaccessibility of these introns to the endonuclease.     

Reduced mortality after the implementation of a protocol for the early detection of severe sepsis

Objective

We evaluate the impact that implementing an in-hospital protocol for the early detection of sepsis risk has on mortality from severe sepsis/septic shock.

Methods

This was a prospective cohort study conducted in 2 phases at 2 general hospitals in Brazil. In phase I, patients with severe sepsis/septic shock were identified and treated in accordance with the Surviving Sepsis Campaign guidelines. Over the subsequent 12 months (phase II), patients with severe sepsis/septic shock were identified by means of active surveillance for signs of sepsis risk (SSR). We compared the 2 cohorts in terms of demographic variables, the time required for the identification of at least 2 SSRs, compliance with sepsis bundles (6- and 24-hour), and mortality rates.

Results

We identified 217 patients with severe sepsis/septic shock (102 during phase I and 115 during phase II). There were significant differences between phases I and II in terms of the time required for the identification of at least 2 SSRs (34 ± 48 vs 11 ± 17 hours; P < .001) and in terms of in-hospital mortality (61.7% vs 38.2%; P < .001).

Conclusion

The early detection of sepsis promoted early treatment, reducing in-hospital mortality from severe sepsis/septic shock.     

Major DNA Polymerases Common to Different Xenopus laevis Cell Types

DNA polymerases from Xenopus laevis oocytes, unfertilized eggs, and kidney cells grown in culture have been characterized. The same three major DNA polymerase activities are present in all cell types examined. We attempt to relate the characteristics of amphibian enzymes to those of mammalian polymerases.