Selective antileishmania activity of 13,28‐epoxy‐oleanane and related triterpene saponins from the plant families Myrsinaceae,Primulaceae, Aceraceae and Icacinaceae

Maesa saponins with the 13,28‐epoxy‐oleanane triterpene core skeleton were described recently to possess strong and selective in vitro and in vivo antileishmania activity. In the absence of direct chemical derivatization possibilities, a structure‐based literature search was carried out to explore a structure‐activity relationship. Crude alcohol extracts from several plant species of Myrsinaceae, Primulaceae, Aceraceae and Icacinaceae were evaluated for in vitro activity against Leishmania infantum intracellular amastigotes and cytotoxicity on MRC‐5_SV2 cells, while the saponin content was evaluated qualitatively by TLC. A clear correlation was found between the presence of close analogue 13,28‐epoxy‐oleanane triterpene saponins and potent and selective antileishmania activity. This was most striking in Maesa species, except for M. macrosepala. Interesting activities were also found in extracts that did not exactly match the TLC characteristics of the Maesa saponin references, as was the case for Ardisia angusta, A. amherstiana, A. caudata, A. gigantifolia, A. roseiflora, Myrsine affinis, Acer brevipes and A. laurinum var. petelotii. This study indicates that the 13,28‐epoxy‐oleanane triterpene moiety is essential for selective antileishmania potential and that several other plant species could still be explored for antileishmania drug discovery. Copyright © 2009 John Wiley & Sons, Ltd.     

Risk Factors for Non-Sentinel Lymph Node Metastases in Patients with Breast Cancer. The Outcome of a Multi-institutional Study

Background In this multi-institutional prospective study, we evaluated whether we could identify risk factors predictive for non-sentinel lymph node (non-SN) metastases in breast cancer patients with a positive sentinel lymph node (SN). Methods In this multi-institutional study, 541 eligible breast cancer patients were included prospectively. Results The occurrence of non-SN metastases was related to the size of the SN metastasis (P = .02), primary tumor size (P = .001), and lymphovascular invasion (P = .07). The adjusted odds ratio was 3.1 for SN micro-metastasis compared with SN isolated tumor cells, 4.0 for SN macro-metastasis versus SN isolated tumor cells, 3.1 for tumor size (>3.0 cm compared with ≤3.0 cm), and 2.0 for lymphovascular invasion (yes versus no). There were no positive non-SNs when the primary tumor size was ≤1.0 cm (n = 24) [95% confidence interval (95% CI) 0%–14.0%]. The proportion of positive non-SNs ranged in a prognostic logistic regression model from 9.7% (95% CI 4.0%–23.0%) for patients with SN isolated tumor cells, tumor size of 1.1–3.0 cm, and without vessel invasion, to 72.6% (95% CI 47.0%–89.0%) for patients with SN macro-metastasis, tumor size >3.0 cm, and with vessel invasion. Conclusion We identified three predictive factors for non-SN metastases in breast cancer patients with a positive SN: size of the SN metastasis; primary tumor size; and vessel invasion. We were not able to identify a specific group of patients with a positive SN in whom the risk for non-SN metastases was less than 5%.     

Effect of childbirth on the course of Crohn's disease; results from a retrospective cohort study in the Netherlands

Background  

Pregnant women with Crohn's disease needs proper counselling about the effect of pregnancy and childbirth on their disease. However, Literature about the effect of childbirth on Crohn's disease is limited. This study examined the effect of childbirth on the course of Crohn's disease and especially perianal Crohn's disease.     

Affectively Salient Meaning in Random Noise: A Task Sensitive to Psychosis Liability

Stable differences in the tendency to attribute meaning and emotional value to experience may represent an indicator of liability to psychosis. A brief task was developed assessing variation in detecting affectively meaningful speech (speech illusion) in neutral random signals (white noise) and the degree to which this was associated with psychometric and familial vulnerability for psychosis. Thirty patients, 28 of their siblings, and 307 controls participated. The rate of speech illusion was compared between cases and controls. In controls, the association between speech illusion and interview-based positive schizotypy was assessed. The hypothesis of a dose-response increase in rate of speech illusion across increasing levels of familial vulnerability for psychosis (controls, siblings of patients, and patients) was examined. Patients were more likely to display speech illusions than controls (odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.4–11.7), also after controlling for neurocognitive variables (OR = 3.8, 95% CI = 1.04–14.1). The case-control difference was more accentuated for speech illusion perceived as affectively salient (positively or negatively appraised) than for neutrally appraised speech illusions. Speech illusion in the controls was strongly associated with positive schizotypy but not with negative schizotypy. In addition, the rate of speech illusion increased with increasing level of familial risk for psychotic disorder. The data suggest that the white noise task may be sensitive to psychometric and familial vulnerability for psychosis associated with alterations in top-down processing and/or salience attribution.     

The influence of temporal resolution in determining pharmacokinetic parameters from DCE‐MRI data

We investigated the influence of the temporal resolution of dynamic contrast‐enhanced MRI data on pharmacokinetic parameter estimation. Dynamic Gd‐DTPA (Gadolinium‐diethylene triamine pentaacetic acid) enhanced MRI data of implanted prostate tumors on rat hind limb were acquired at 4.7 T, with a temporal resolution of ～5 sec. The data were subsequently downsampled to temporal resolutions in the range of 15 sec to 85 sec, using a strategy that involves a recombination of k‐space data. A basic two‐compartment model was fit to the contrast agent uptake curves. The results demonstrated that as temporal resolution decreases, the volume transfer constant (K^trans) is progressively underestimated (～4% to ～25%), and the fractional extravascular extracellular space (v_e) is progressively overestimated (～1% to ～10%). The proposed downsampling strategy simulates the influence of temporal resolution more realistically than simply downsampling by removing samples. Magn Reson Med 63:811–816, 2010. © 2010 Wiley‐Liss, Inc.     

A fetal scalp electrode as a simple aid in the search for a lost needle fragment during sacrospinous ligament fixation

A needle fragment was lost during a sacrospinous ligament fixation. This was recognized during the procedure, but could not be found at that moment. The patient complained of severe buttock pain postoperatively. The needle fragment was localized on CT scan of the pelvis. A fetal scalp electrode helped as a search device to localize the needle on X-ray during the secondary surgery. The patient was operated successfully and was free of pain after 6 weeks.     

Epiphora due to compression of the lacrimal sac by a supernumerary blind sac

A 23-year-old male had suffered from epiphora in the left eye since childhood. There was no history of infection or trauma. A supernumerary punctum was seen in the left lacrimal caruncle on examination. Subsequent dacryocystography and computer tomography showed a blind-ended sac that was connected to the supernumerary punctum, but not to the normally developed nasolacrimal system. When distended with secretion, this blind-ended lacrimal sac caused compression and obstruction of the normal lacrimal drainage pathway, which led to epiphora. The epiphora disappeared after surgical removal of the supernumerary system.