Coordinated Analysis of Organic Matter in Primitive Meteorites

Carbonaceous chondrites (CC) preserve a diverse range of organic matter formed within cold interstellar environments, the solar nebula, and during subsequent parent body asteroidal processing. This organic matter maintains a unique geochemical and istopic record of organic evolution [1-4]. Bulk studies of organics within CC have revealed a complex array of organic species. However, bulk studies invariably involve solvent extraction, resulting in a loss of spatial context of the host mineral matrix [3, 5]. Correlated in situ chemical and isotopic studies suggest preservation of interstellar organics in the form of spherical, often hollow, micrometer sized organic nano-globules. Nanoglobules often exhibit significant delta 15N and delta D enrichments that imply formation through fractionation of ion-molecule reactions within cold molecular clouds and/or the outer protoplanetary disk [5]. In situ studies such as 6-8 are necessary to understand the organic evolutionary stages of nanoglobules and other components in the nebula and parent body [7]. We carried out coordinated in situ micrometer-scale chemical, mineralogical and isotopic studies of the Murchison (CM2), QUE 99177 (CR3), and Tagish Lake (C2 Ung) CC. These studies were performed using fluorescent microscopy, two-step laser mass spectrometry (microL2MS), NanoSIMS, and Scanning Electron Microscopy (SEM) with Energy Dispersive X-Ray Spectroscopy (EDX). Comparative analysis of three different meteorites will help reveal the effects of parent body processes on the chemistry and isotopic composition of organic matter

In Situ Coordinated Analysis of Carbonaceous Chondrite Organic Matter

Microanalytical studies of carbonaceous chondrites (CCs) have identified a vast array of isotopically, chemically and texturally distinct organic components. These components were synthesized and processed within a range of physical and chemical environments, including the interstellar medium, the solar nebula and within asteroids. The nature and abundance of these molecules can be used to unravel the geochemical and isotopic record of their origins as well as their subsequent evolutionary journey

Influence of cytogenetic abnormalities on outcome after allogeneic bone marrow transplantation for acute myeloid leukemia in first complete remission

AbstractCytogenetic abnormalities detected at diagnosis are recognized as important in predicting response to chemotherapy in acute myeloid leukemia (AML). However, there is controversy concerning the prognostic significance of karyotype for outcome after allogeneic bone marrow transplantation (allo-BMT) performed in first complete remission (CR1). This single-institution report describes allo-BMT for AML in CR1 and the effect of diagnostic cytogenetic findings on the results of that treatment. Between August 1981 and December 1999, 93 patients underwent related donor (n = 82) or unrelated donor (n = 11) BMT. Conditioning and GVHD prophylaxis were achieved predominantly with busulfan and cyclophosphamide and with cyclosporine and methotrexate, respectively. Seventy-nine (85%) of 93 patients had successful marrow karyotyping at diagnosis, and the patients were categorized into 3 prognostic groups based on the British Medical Research Council AML 10 trial classification: 15 patients(19%) were classified as having favorable risk [inv(16), t(8;2 1), t(15;17)]; 55 (70%) as having intermediate risk [no abnormality, +8, +21, +22, del(7q), del(9q), 11q23 rearrangement, and other numerical or structural abnormalities]; and 9 (11%) as having adverse risk [-5, del(5q), -7, 3q rearrangements, > or = 5 abnormalities, t(6;9), t(9;22)]. The median follow-up was 93 months (range, 16-241 months). The overall survival (OS) rate, event-free survival (EFS) rate, relapse rate, and treatment-related mortality (TRM) were not statistically different between the groups. The 5-year actuarial EFS rates for favorable, intermediate, and adverse risk groups were 58% (95% confidence interval [CI], 29%-79%), 58% (95% CI, 43%-70%), and 67% (95% CI 28%-88%), respectively. Reclassification of patients into cytogenetic prognostic subgroups according to Southwest Oncology Group criteria did not change these results. In univariate analysis, the only variable found to have a prognostic influence on OS (P = .04) and TRM (P = .03) was the type of donor (unrelated donor was linked to a worse prognosis), which was confirmed in multivariate analysis. Our study suggests that presentation karyotype has less prognostic significance for outcome following allo-BMT than for outcome following conventional chemotherapy. In particular, AML patients with poor prognostic cytogenetic changes in CR1 who are unlikely to be cured with chemotherapy alone may benefit from allo-BMT.Biol Blood Marrow Transplant 2002;8(8):435-43

Early Stem Cell Transplantation for Refractory Acute Leukemia after Salvage Therapy with High-Dose Etoposide and Cyclophosphamide

AbstractPrimary refractory acute leukemia (AL) has a poor prognosis, although some patients can be salvaged with allogeneic stem cell transplantation (SCT). Induction of complete remission (CR) with conventional chemotherapy before SCT may improve outcome in this patient population. Between March 1991 and October 2003, 59 adults with primary refractory AL were treated with continuous-infusion etoposide (VP) 2.4 to 3.0 g/m2 followed by cyclophosphamide (Cy) 6.0-7.2 g/m2 intravenously over 3 to 4 days with the intention of proceeding to SCT in CR1. Forty-two patients had acute myelogenous leukemia (AML), 13 patients had acute lymphoblastic leukemia (ALL), and 4 patients had acute biphenotypic leukemia. The most frequent nonhematologic toxicities were oral mucosal, gastrointestinal, and hepatic toxicities (44%, 20%, and 15% of patients, respectively). Thirty-two (57%) of 56 evaluable patients entered CR1 with a median time to platelet and neutrophil recovery of 22 and 26 days, respectively. CR1 rates were similar in AML (54%) and ALL/acute biphenotypic leukemia (67%; P = .52), and analysis of baseline characteristics did not reveal any predictors of response to VP/Cy. Twenty-nine of 32 CR1 patients subsequently underwent SCT (24 allogeneic and 5 autologous). Estimated 5-year event-free survival (EFS) and overall survival for the entire cohort are 23% and 26%, respectively. In the allogeneic SCT group, 5-year EFS was 52% for AML patients and 14% for ALL patients (P = .04), and only male sex was predictive of a favorable outcome (P = .03). VP/Cy is able to induce CR1 in most patients with primary refractory AL with an acceptable toxicity profile. Subsequent allogeneic SCT can lead to long-term EFS in a significant proportion of patients

Entering a new era of body indices: the feasibility of a body shape index and body roundness index to identify cardiovascular health status.

BACKGROUND: The Body Mass Index (BMI) and Waist Circumference (WC) are well-used anthropometric predictors for cardiovascular diseases (CVD), but their validity is regularly questioned. Recently, A Body Shape Index (ABSI) and Body Roundness Index (BRI) were introduced as alternative anthropometric indices that may better reflect health status. OBJECTIVE: This study assessed the capacity of ABSI and BRI in identifying cardiovascular diseases and cardiovascular disease risk factors and determined whether they are superior to BMI and WC. DESIGN AND METHODS: 4627 Participants (54±12 years) of the Nijmegen Exercise Study completed an online questionnaire concerning CVD health status (defined as history of CVD or CVD risk factors) and anthropometric characteristics. Quintiles of ABSI, BRI, BMI, and WC were used regarding CVD prevalence. Odds ratios (OR), adjusted for age, sex, and smoking, were calculated per anthropometric index. RESULTS: 1332 participants (27.7%) reported presence of CVD or CVD risk factors. The prevalence of CVD increased across quintiles for BMI, ABSI, BRI, and WC. Comparing the lowest with the highest quintile, adjusted OR (95% CI) for CVD were significantly different for BRI 3.2 (1.4-7.2), BMI 2.4 (1.9-3.1), and WC 3.0 (1.6-5.6). The adjusted OR (95% CI) for CVD risk factors was for BRI 2.5 (2.0-3.3), BMI 3.3 (1.6-6.8), and WC 2.0 (1.6-2.5). No association was observed for ABSI in both groups. CONCLUSIONS: BRI, BMI, and WC are able to determine CVD presence, while ABSI is not capable. Nevertheless, the capacity of BRI as a novel body index to identify CVD was not superior compared to established anthropometric indices like BMI and WC

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes