NIFT-P: Are they indolent tumors? Results of a multi-institutional study

Background

Encapsulated follicular variant of papillary thyroid carcinoma has recently been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features on the basis of its highly indolent behavior, as proposed by an international group of experienced thyroid pathologists.

Permissive role of thrombopoietin and granulocyte colony-stimulating factor receptors in hematopoietic cell fate decisions in vivo

The question of whether extracellular signals influence hematopoiesis by instructing stem cells to commit to a specific hematopoietic lineage (instructive model) or solely by permitting the survival and proliferation of predetermined progenitors (permissive model) has been controversial since the discovery of lineage-dominant hematopoietic cytokines. To study the potential role of cytokines and their receptors in hematopoietic cell fate decisions, we used homologous recombination to replace the thrombopoietin receptor gene (mpl) with a chimeric construct encoding the extracellular domain of mpl and the cytoplasmic domain of the granulocyte colony-stimulating factor receptor (G-CSFR). This chimeric receptor binds thrombopoietin but signals through the G-CSFR intracellular domain. We found that, despite the absence of a functional mpl signaling domain, homozygous knock-in mice had a normal platelet count, indicating that in vivo the cytoplasmic domain of G-CSFR can functionally replace mpl signaling to support normal megakaryopoiesis and platelet formation. This finding is compatible with the permissive model, according to which cytokine receptors provide a nonspecific survival or proliferation signal, and argues against an instructive role of mpl or G-CSFR in hematopoietic cell fate decisions.     

Endogenous survivin modulates survival and proliferation in UVB-treated human keratinocytes

Abstract:  Survivin is a bi-functional member of inhibitor of apoptosis protein family, as it is able to both inhibit apoptosis and to regulate cell cycle. We investigated the role of survivin in human keratinocytes under normal conditions and during UVB irradiation. Survivin siRNA decreases proliferation and induces apoptosis in human keratinocytes, in a mode consistent with the mitotic catastrophe. Low doses UVB increase survivin expression at earlier times, while high doses down-regulate survivin level. Low doses UVB induce cell cycle arrest in G2/M, while high doses UVB cause apoptosis. Moreover, overexpression of survivin protects keratinocytes from UVB-induced apoptosis, and silencing of survivin renders keratinocytes more susceptible to UVB-induced cell death. Finally, survivin siRNA increases UVB-induced reduction of cell proliferation. Taken together, these results indicate that survivin plays a critical role in epidermal homeostasis in normal conditions and during UVB exposure, with possible implication in skin carcinogenesis.     

Influence of surgical treatment timing on mortality from necrotizing soft tissue infections requiring intensive care management

Purpose  Surgical treatment is crucial in the management of necrotizing soft tissue infections (NSTIs). The aim of this study was to determine the influence of surgical procedure timing on hospital mortality in severe NSTI. Methods  A retrospective study including 106 patients was conducted in a medical intensive care unit equipped with a hyperbaric chamber. Data regarding pre-existing conditions, intensive care and surgical management were included in a logistic regression model to determine independent factors associated with hospital mortality. Results  Overall hospital mortality was 40.6%. In multivariate analysis, underlying cardiovascular disease, SAPS II, abdominoperineal compared to limb localization, time from the first signs to diagnosis <72 h, and time from diagnosis to surgical treatment >14 h in patients with septic shock were independently associated with hospital mortality. Conclusion  In patients with NSTI and septic shock, hospital mortality is influenced by the timing of surgical treatment.     

Combination of olfactory ensheathing cells with local versus systemic cAMP treatment after a cervical rubrospinal tract injury

The failure of CNS axons to regenerate following traumatic injury is due in part to a growth‐inhibitory environment in CNS as well as a weak intrinsic neuronal growth response. Olfactory ensheathing cell (OECs) transplants have been reported to create a favorable environment promoting axonal regeneration, remyelination, and functional recovery after spinal cord injury. However, in our previous experiments, OEC transplants failed to promote regeneration of rubrospinal axons through and beyond the site of a dorsolateral funiculus crush in rats. Rubrospinal neurons undergo massive cell atrophy and limited expression of regeneration‐associated genes after axotomy. Using the same injury model, we tested the hypothesis that treatment of the red nucleus with cAMP, known to stimulate the intrinsic growth response in other neurons, will promote rubrospinal regeneration in combination with OEC transplants. In addition, we assessed a systemic increase of cAMP using the phosphodiesterase inhibitor rolipram. OECs prevented cavity formation, attenuated astrocytic hypertrophy and the retraction of the axotomized rubrospinal axons, and tended to reduce the overall lesion size. OEC transplantation lowered the thresholds for thermal sensitivity of both forepaws. None of our treatments, alone or in combination, promoted rubrospinal regeneration through the lesion site. However, the systemic elevation of cAMP with rolipram resulted in greater numbers of OECs and axonal density within the graft and improved motor performance in a cylinder test in conjunction with enhanced rubrospinal branching and attenuated astrocytic hypertrophy. © 2010 Wiley‐Liss, Inc.     

Misoprostol compared with methylergometrine for the prevention of postpartum haemorrhage: a double-blind randomised trial.

OBJECTIVE: To compare the efficacy and side effects of misoprostol, compared with methylergometrine, for the prevention of postpartum haemorrhage. DESIGN: A double-blind, randomised clinical trial of 200 women with apparently normal pregnancies. SETTING: University teaching hospital. PARTICIPANTS: Two hundred women with apparently normal pregnancies. METHODS: After the baby had been born, all women received two capsules by mouth and the contents of an ampule by intravenous injection. Each woman only received one active product. The capsules contained either a total of 600 microg misoprostol or placebo, and the ampule 200 microg of methylergometrine or placebo. MAIN OUTCOME MEASURES: Need for further oxytocic drugs, blood pressure, the presence of side effects, mean haemoglobin and haematocrit three days after delivery. RESULTS: Two hundred women completed the study (100 received methylergometrine and 100 misoprostol). Postpartum haemorrhage occurred in 4.3% of the methylergometrine group and 8.3% of the misoprostol group (P = 0.57). The need for further oxytocic drugs was 4.4% and 12.8% after methylergometrine and misoprostol, respectively (P = 0.065). One hour after the birth of the baby there was no difference in the mean systolic blood pressure (117 +/- 12 mmHg versus 115 +/- 11 mmHg) (P = 0.26) or the mean diastolic blood pressure (72 +/- 10 mmHg versus 71 +/- 11 mmHg for the groups receiving methylergometrine or misoprostol, respectively) (P = 0.97). The mean temperature in the misoprostol group rose to 37.4 degrees C, compared with 37 degrees C in the methylergometrine group (P < 0.0001). In the misoprostol group 34% developed fever (> 38 degrees C) compared with 3% in the methylergometrine group (P < 0.0001). Shivering (visual analogue score > or = 8) also occurred more often after misoprostol (42%) than after methylergometrine (8.5%) (P < 0.0001). The haemoglobin level (g/dL) on the third postpartum day was similar for both groups ( 11.0 and 11.2 for methylergometrine and misoprostol, respectively) (P = 0.39). CONCLUSIONS: This study suggests that although protection from postpartum haemorrhage using parenteral methylergometrine and oral misoprostol is nearly equal, misoprostol is associated with more side effects.