Concomitant symptomatic cardiac sarcoidosis and systemic sclerosis with cardiac involvement: a case report.

Sarcoidosis and systemic sclerosis are two inflammatory multisystemic disorders of unknown etiology that may be life-threatening especially when there is cardiac involvement. Both diseases may coexist, however, there are very few case reports of patients with both cardiac sarcoidosis and systemic sclerosis in the literature. We report the case of a 72-year-old female who was initially referred for dyspnea. A chest computed tomography scan showed multiple hilar and mediastinal adenopathy with a non-specific opacity in the middle pulmonary lobe. FDG-PET-scan showed increased FDG uptake in the adenopathy, the middle lobe and the right ventricular free wall. Sarcoidosis was confirmed with a lung biopsy. Both electrocardiogram and echocardiogram were normal. Four months later, the patient developed a high-grade atrioventricular block deemed secondary to her cardiac sarcoidosis. Two years later, the patient was referred to a rheumatologist for severe Raynaud's symptoms, sclerodactyly and acrocyanosis. After thorough investigations, a diagnosis of limited cutaneous systemic sclerosis with systemic and cardiac sarcoidosis was made. This case demonstrates that both cardiac sarcoidosis and systemic sclerosis may coexist. In the literature, either disease may come first. In cases where cardiac symptoms appear after the diagnosis of concomitant sarcoidosis and systemic sclerosis, it might be difficult for clinicians to confirm which disease is responsible for the heart involvement. This is important since early cardiac sarcoidosis treatment should be done to prevent major complications and may well differ from systemic sclerosis treatment. In this review, we discuss the main clinical manifestations and imaging findings seen with cardiac disease secondary to sarcoidosis and systemic sclerosis.

Maximizing lymph node dissection from fresh lung cancer specimens.

Evaluation of lymph nodes during lung cancer resection is essential for pathologic staging and adjuvant treatment decisions. We developed a standardized approach for grossing resected lobes and segments to better assign the N1 category to hilar and peripheral lymph nodes. Lung specimens were dissected centrifugally from the bronchial stump, and all lymph nodes at the segmental and subsegmental bifurcations were removed. When combined with mediastinal lymph node dissection, this approach will likely maximize the number of lymph nodes analysed and improve the accuracy of pathologic N descriptor classification.

From triclosan toward the clinic: discovery of nonbiocidal, potent FabI inhibitors for the treatment of resistant bacteria.

In this paper, we present some elements of our optimization program to decouple triclosan's specific FabI effect from its nonspecific cytotoxic component. The implementation of this strategy delivered highly specific, potent, and nonbiocidal new FabI inhibitors. We also disclose some preclinical data of one of their representatives, 83, a novel antibacterial compound active against resistant staphylococci and some clinically relevant Gram negative bacteria that is currently undergoing clinical trials.

Synthesis and biological activity of phosphonate analogues and geometric isomers of the highly potent phosphoantigen (E)-1-hydroxy-2-methylbut-2-enyl 4-diphosphate.

Gammadelta-T-lymphocytes contribute to innate immunity and are selectively activated by nonpeptide phosphorylated molecules (so-called phosphoantigens) produced by organisms responsible for causing a broad range of infectious diseases. gammadelta-T-cells are also activated by synthetic phosphoantigens and are cytotoxic to tumor cells. Here we report the synthesis, NMR characterization, and comparative biological evaluation of new pyrophosphate, phosphonate, and pyrophosphonate monoesters whose structures correspond to isosteric analogues and stereoisomers of the highly potent isoprenoid metabolite ( E)-1-hydroxy-2-methylbut-2-enyl 4-diphosphate called HDMAPP (hydroxy-dimethyl-allyl pyrophosphate). Both pyrophosphate and pyrophosphonate series elicit promising gammadelta-T-cell stimulatory responses in vitro, the pyrophosphonate ester (C-HDMAPP) being by far more stable than its parent pyrophosphate ester (HDMAPP) with improved ADMET properties and a similar pharmacodynamic profile based on in vivo studies in nonhuman primate. In both series, we found that E-stereoisomers are the most active derivatives and that Z-stereoisomers show very marginal bioactivity levels. These results indicate that the use of bioisosteric analogues of HDMAPP may represent promising new leads for immunotherapy.