Biventricular thrombus and associated myocardial infarction in a rheumatoid arthritis patient: a case report and literature review

Autoimmune diseases including rheumatoid arthritis have an increased incidence of cardiovascular disease. Rheumatoid arthritis (RA) confers a prothrombotic state and is associated with venous thrombosis, but its association with arterial thrombosis and embolism is not clear. In present report, we introduce a unique case of a 42-year-old woman with RA, who was admitted to the emergency service with back pain and diagnosed as having large right and left ventricular thrombus and myocardial infarction, associated with embolization of the thrombus. We also review the literature about RA and arterial and intraventricular thrombosis.     

Genomic structure of proton-coupled oligopeptide transporter hPEPT1 and pH-sensing regulatory splice variant

Proton-coupled oligopeptide transporter PEPT1 facilitates the transport of dipeptides and peptoid drugs (including antibiotics) across the cell membranes of endothelial and epithelial cells. Substrate transport by the proton symport is driven by pH gradients, while the profile of pH sensitivity is regulated by a closely related protein. hPEPT1-RF. We investigated the genomic structure of hPEPT1 and hPEPT1-RF. Analysis of the high-throughput genomic sequence (HTGS) database revealed that hPEPT1 and hPEPT1-RF are splice variants encoded by the same gene located in chromosome 13, consisting of 24 exons. hPEPT1 is encoded by 23 exons and hPEPT1-RF by 6 exons. Coding sequences of hPEPT1-RF share 3 exons completely and 2 exons partially with hPEPT1. The genomic organization of hPEPT1 shows high similarity with its mouse orthologue. Exon-intron boundaries occur mostly in the loops connecting transmembrane segments (TMSs), suggesting a modular gene structure reflecting the TMS-loop repeat units in hPEPT1. The putative promoter region of hPEPT1 contains TATA boxes and GC-rich regions and a potential insulin responsive element.     

Large perilymph fistulas

Perilymph fistulas may manifest themselves either by otologic symptoms, as in cases of small fistulas, or primarily through neurologic symptoms, as with large fistulas. A case history is presented of a 3-year-old girl with recurrent bouts of meningitis who was found to have a large perilymph fistula. She had a right undeveloped cochlea and labyrinth, as well as multiple defects of the medial wall of her middle ear. The only way of preventing the recurrent bouts of bacterial meningitis in cases of large perilymph fistulas is surgical repair. Our conclusion is that, considering the problems involved in cases of large congenital perilymph fistulas, a simple closure of the fistula is not sufficient and the method of choice is obliteration of a deeper structure--such as the vestibule itself.     

A Model of Cancer Evolution Implications for Novel Treatment Strategies

Cancer remains one of the main killers among all diseases, defying tremendous efforts in the search for effective treatments. Malignant transformation results in characteristic changes of the cell's functions and shape, such as unregulated and unlimited proliferation, loss of cellular senescence, partial reversal of differentiation, ability to grow in suspension, and invasiveness. Often, initial treatment is quite effective in eliminating a majority of the tumor, for example with use of chemotherapy, only to have more resistant and aggressive cancer cells reappear and form metastases. This causes eventual death of the patient because most treatments have lost efficacy. Are there underlying principles guiding this microevolution of a transformed cell into a fully invasive cancer? And if so, can we avoid emergence of more resistant cancer cells through treatment-induced selection pressure by applying therapies that anticipate and steer the evolution of a particular cancer? To address such questions, this perspective provides an overview of the biology and strategies, including use of smart nanodevices capable of homing in on the cancer cell.     

Clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C) below age 1

Clinical Rheumatology -     

How can the hooded seal dive to a depth of 1000 m without rupturing its tympanic membrane? A morphological and functional study.

Recent studies using a satellite-linked dive recorder have shown that the hooded seal (Cystophora cristata), a common Arctic pinniped, can dive to a depth of > 1000 m and stay submerged for close to 1 h. At these depths the water pressure reaches 100 atm, entailing obvious risk of serious damage to the hearing apparatus, mainly the tympanic membrane (TM) and middle ear (ME). We dissected and photodocumented the temporal bones of five newborn and three adult hooded seals in order to study the temporal bone structure and reveal its protective mechanisms for extreme pressure changes. Specimens were sectioned and stained for light microscopy. The thicknesses of the pars tensa and pars flaccida were found to average 60 and 180 microm, respectively. The ME cavity hosts a cavernous tissue of thin-walled vessels beneath the modified respiratory epithelium. The ME and external ear canal (EAC) volumes can be altered appreciably by filling/emptying the cavernous tissue with blood. The ossicles were fixed by contracting the tensor tympani and stapedius muscles simultaneously with complete occlusion of the EAC. According to Boyle's law, the volume of the gas-filled ME cavity at a depth of 1000 m is only 1% of its volume at the surface of the sea. Ascent from such a depth allows the gas in the ME cavity to expand, causing the TM to bulge laterally. This movement is counteracted by a reduction in the blood volume inside the cavernous sinuses, action in the tensor tympani and stapedius muscles and discharge of gas through the Eustachian tube. The presence of a firm, broad-based exostosis in the floor of the EAC lateral to the TM helps to obstruct the EAC.     

The fluoropyrimidines: Biochemical mechanisms and design of clinical trials

Summary Our understanding of the biochemical events of fluoropyrimidine-induced cytotoxicity remains incomplete. However, we have a good perception of the activation and degradation pathways of these agents. Additionally, from studies performed in vitro we are gaining a new appreciation of the interactions between methotrexate and the fluoropyrimidines. These studies suggest that the common clinical practice of simultaneously administering methotrexate and 5-fluorouracil may be disadvantageous. Several simple scheduling modifications of combination therapies with these two drugs could lead to improved clinical efficacy and deserve further investigation.