Functionalization of α-hydroxyphosphonates as a convenient route to N-tosyl-α-aminophosphonates

Direct conversion of the α-hydroxyl group by para-toluenesulfonamide to yield α-(N-tosyl)aminophosphonates is reported. α-Aminophosphonates 23a,b–37a,b were obtained from the corresponding α-hydroxyphosphonates 6a,b–21a,b in the presence of K₂CO₃, via the retro-Abramov reaction of the appropriate aldehydes, 1–5. The subsequent formation of imines with simultaneous addition of diethyl phosphite provided access to the α-sulfonamide phosphonates 23a,b–37a,b with better diastereoselectivity than in the case of the Pudovik reaction. The mechanism for this transformation is proposed herein. When Cbz N-protected aziridine 9a,b and phenylalanine analogue 12a,b were exploited, intramolecular substitution was observed, leading to the corresponding epoxide 38 as the sole product, or oxazolidin-2-one 39 as a minor product. Analogous substitution was not observed in the case of proline 18a,b and serine 21a,b derivatives.

The reaction mechanism and diastereoselectivity of the direct transformation of α-hydroxyphosphonates 6a,b–21a,b by para-toluenesulfonamide, yielding α-(N-tosyl)aminophosphonates 23a,b–37a,b under K₂CO₃ conditions are presented.     

Incidental findings in multislice computed tomography prior to transcatheter aortic valve implantation: frequency,clinical relevance and outcome

Multislice computed tomography (MSCT) has emerged as the mainstay in patients planned for transcatheter aortic valve implantation (TAVI). Incidental findings (IF) in MSCT are common. However, the exact incidence, clinical relevance and further consequences of IF are unclear and it is controversial whether IF adversely affect patients’ outcome. We analyzed MSCT data of 1050 patients screened for TAVI between January 2011 and December 2014. Median follow-up of patients was 20 months. In total, 3194 IF were identified, which were classified into clinically non-relevant IF (2872, 90%) and clinically relevant IF (322, 10%). In 25% of patients (258/1050) at least one clinically relevant IF was present. Age (80?±?7 vs. 80?±?7 years; p?=?0.198) and EuroSCORE II (3.6% [2.1–5.7] vs. 3.6% [2.1–5.9]; p?=?0.874) was similar between patients with and without a clinically relevant IF. TAVI was performed less frequently in patients with a clinically relevant IF (76% vs. 85%; p?<?0.001), with more patients receiving surgical aortic valve replacement in that group (14% vs. 11%; p?=?0.042), possibly due to the high rate of incidental aneurysms of the ascending aorta (n?=?48). If TAVI was performed mortality did not differ (30-days: 4% vs. 3%; p?=?0.339, 1-year: 11% vs. 14%; p?=?0.226) between patients with and without a clinically relevant IF. Our study is the largest study to analyze prevalence, clinical relevance and therapeutic consequences of IF during screening for TAVI. IF in pre-procedural MSCT are common and clinically relevant in one-quarter of patients. However, these findings had no impact on overall mortality.     

Oncogenicity in newborn and adult Syrian hamsters of SV40 temperature-sensitive (ts) mutants.

Newborn and adult Syrian hamsters were injected with wild-type SV40 and its temperature-sensitive (ts) mutants A30, A209, A239, B201 and BC210. In contrast to wild-type SV40, ts A30, ts A 239 and ts BC210 were oncogenic in adult hamsters inducing tumors after almost the same latent period as wild type SV40 in newborns but in lower number of animals. Study of TSTA in some tumors (1 generation) induced in newborn and adult hamsters by wild type SV40 and its ts mutants (with the use of immunogenicity and immunosensitivity tests) revealed no significant difference among compared tumors: most of them were immunogenic and immunosensitive. In contrast hamster embryo cells in vitro transformed by SV40 ts A30, ts A239 and ts A209 mutants, studied at different passage levels were all immunoresistant during about 30 in vitro passages and in most cases 10--100 times less immunogenic than hamster embryo cells in vitro transformed by wild type SV40. At higher passage level in some of these lines expression of TSTA improved. The data obtained are discussed in connection with the recently demonstrated [5] significant quantitative difference in tumor specific transplantation antigen activity in hamster cells in vivo and vitro infected, or transformed by wild type SV40 and its ts A mutants.     

Antiphospholipid antibodies before and after liver transplantation

OBJECTIVE: The aim of this study was to determine whether liver transplantation of patients with antiphospholipid antibodies (APA) is 1) adversely affected with vascular thrombosis and 2) whether such antibodies persist post transplantation. METHODS: Twelve patients with APA awaiting transplant were identified and characterized biochemically and immunologically. Each had the level of APA determined using commercially available enzyme-linked immunoassay kits before, during, and after liver transplantation. RESULTS: No patient in this series experienced a transplant-related vascular thrombosis. The titer of APA fell to levels at or below those present in normals and remained low in two of 12 or undetectable in 10 of 12 patients 1 yr after liver transplantation. CONCLUSIONS: We reached the following conclusions: 1) Antiphospholipid positivity does not identify patients at high risk for post-transplant vascular thrombosis. 2) The levels of antiphospholipid present in sera pretransplant fell during transplantation and remained low or undetectable 1 month and 1 yr post transplantation.     

Splenic rupture in infectious disease: splenectomy or conservative treatment? Report of three cases

INTRODUCTION: Spontaneous splenic ruptures are rare but life-threatening complications of infectious diseases. Splenectomy is still the treatment of choice but numerous recent reports have documented favorable outcome with conservative treatment. EXEGESIS: We report three cases of splenic rupture occurring respectively with infectious mononucleosis, P. vivax infection and dengue fever. Diagnosis, treatment and indications are reviewed, an approach to management is suggested. The study included three military men respectively aged 23, 24 and 35 years, admitted for acute abdominal pain in the left upper quadrant. The abdominal computed tomography confirmed partial rupture (splenic hematoma) in the first two cases, and an hemoperitoneum in the dengue case. Splenic ruptures can reveal or complicate an evolving infection. Rupture can happen spontaneously or as a result of trauma, which may be minor and unnoticed. The typical presentation is acute, but progressive forms are described. The diagnosis is made by ultrasound and CT scan. Splenectomy dogma tends to be supplanted by conservative treatment. Non-operative management can be successful if appropriate criteria and a long period of follow-up are applied in carefully selected cases. When an operative approach is selected, conservative surgical treatment is attractive. Splenectomy should be reserved for patients with uncontrollable rupture or with recurrent splenic bleeding. CONCLUSION: Spontaneous splenic rupture are uncommon in infectious diseases. A multidisciplinary management is necessary. A conservative treatment should be considered in selected, closely monitored patients.     

Inflammatory pseudotumor of lymph node

INTRODUCTION: Inflammatory pseudotumor of lymph node is a rare case in the etiology of fever of unknown origin. OBSERVATION: We report the observation of a woman, aged 40, hospitalized with intermittent fever revealing under-diaphragm adenopathy related to inflammatory pseudotumor of lymph node. CONCLUSION: Inflammatory pseudotumor of lymph node is a rare pathology whose nosological definition is unclear. It should probably be considered as belonging to a category different from the inflammatory pseudotumor of other organs. The diagnosis presents itself in case of isolated adenopathy or prolonged fever and is based on an anatomopathology that essentially calls to mind a lymphoma. The evolution of the condition is shown to be favorable : it can lead to a spontaneous remission, or call for a non-steroid anti-inflammatory treatment, or a steroid therapy.     

Virulence and thrombocyte affectation of two Aspergillus terreus isolates differing in amphotericin B susceptibility

Aspergillus terreus-induced invasive infections exhibit high lethality, partly due to the intrinsic resistance for amphotericin B (AmB). We compared the virulence and pathogenesis of an AmB-resistant isolate of A. terreus (ATR) with that of a rare variant showing enhanced sensitivity for AMB (ATS). The modifications that result in enhanced AmB sensitivity of isolates are not associated with reduced virulence in vivo; instead, the ATS-infected mice died even faster than the ATR-infected animals. Since A. terreus enters the blood stream in most patients and frequently induces thrombosis, we studied a putative correlation between virulence of the two A. terreus isolates and their effect on thrombocytes. Those mice infected with the more virulent ATS isolate had lower thrombocyte numbers and more phosphatidylserine exposure on platelets than ATR-infected mice. In vitro experiments confirmed that ATS and ATR differ in their effect on thrombocytes. Conidia, aleurioconidia and hyphae of ATS were more potent than ATR to trigger thrombocyte stimulation, and thrombocytes adhered better to ATS than to ATR fungal structures. Furthermore, ATS secreted more soluble factors that triggered platelet stimulation than ATR. Thus, it might be suggested that the capacity of a fungal isolate to modulate thrombocyte parameters contributes to its virulence in vivo.