Ureteropelvic junction obstruction caused by metastatic cholangiocarcinoma

We describe the rare case of a 61-year-old female with right ureteropelvic junction (UPJ) obstruction caused by metastatic cholangiocarcinoma. Her past medical history was notable for cholangiocarcinoma treated with neoadjuvant chemoradiation and two orthotopic liver transplants six years earlier. Urology was consulted when she presented with flank pain and urinary tract infection. Diagnostic workup demonstrated right UPJ obstruction. She was managed acutely with percutaneous nephrostomy. She subsequently underwent robotic pyeloplasty and intrinsic obstruction of the UPJ was discovered. Histological examination revealed adenocarcinoma, consistent with systemic recurrence of the patient\u27s known cholangiocarcinoma

The Stac Fada “impact ejecta” layer: not what it seems

The Stac Fada Member (SFM) forms part of the Stoer Group of the Torridonian of NW Scotland. The SFM is unique in the Torridonian, being characterized by the presence of greenish altered glass clasts. Its origin has been debated for decades with several hypotheses being proposed but all invoking some connection with volcanic activity in the region. More recently, Amor et al. suggested that the SFM represents “a chord section through the continuous ejecta blanket surrounding an impact crater”. Here, we confirm the presence of shocked material within the SFM and then discuss its origin

Alemtuzumab-induced remission of multiple sclerosis-associated uveitis

Purpose The purpose of the study was to report a case of multiple sclerosis (MS)-associated uveitis refractory to conventional immunosuppressants, with subsequent remission following treatment with alemtuzumab. Methods Case report Patient was treated with intravenous alemtuzumab, a lymphocyte depleting anti-CD52 monoclonal antibody that has recently been approved for use in relapsing MS. Results A 17-year-old female presented with bilateral optic neuritis and subsequently bilateral intermediate uveitis and secondary macular oedema. She was diagnosed with active relapsing MS for which she received treatment with alemtuzumab. The intraocular inflammation previously refractory to conventional immunosuppressants responded to alemtuzumab, inducing remission. Conclusions To our knowledge, this is the first such report of alemtuzumab treatment in MS-associated ocular inflammatory disease and may demonstrate a potential utility for this drug in related conditions

Alemtuzumab for multiple sclerosis: Long term follow-up in a multi-centre cohort

Background: Alemtuzumab has recently been approved for treatment of relapsing MS, but concerns remain about its use since long-term studies of adverse events remain limited. Furthermore, a clear understanding of its application and durability of effect in clinical practice has yet to evolve. Objectives: To investigate long-term efficacy and safety outcomes in a multicentre cohort of patients treated with alemtuzumab. Methods: Patients treated from 2000 and followed-up at three regional centres were identified. Baseline and prospective data were obtained and validated by clinical record review. Results: One hundred patients were identified with a mean follow-up of 6.1 years (range 1–13). Forty patients were retreated with at least one further treatment cycle. Annualized relapse rates fell from 2.1 to 0.2 (p<0.0001) post-treatment and were sustained for up to eight years of follow-up. Mean change in EDSS score was +0.14. Forty-seven patients developed secondary autoimmunity. Conclusion: Observed reduction in relapse rates reflected those reported in clinical trials, but we were unable to corroborate previous observations of disability reversal. 40% of patients required additional treatment cycles. Autoimmune adverse events were common, occurring at a higher rate than previously reported, but were largely predictable, and could be managed effectively within a rigorous monitoring regime

The prosequence of procaricain forms an α-helical domain that prevents access to the substrate-binding cleft

AbstractBackground Cysteine proteases are involved in a variety of cellular processes including cartilage degradation in arthritis, the progression of Alzheimer's disease and cancer invasion: these enzymes are therefore of immense biological importance. Caricain is the most basic of the cysteine proteases found in the latex of Carica papaya. It is a member of the papain superfamily and is homologous to other plant and animal cysteine proteases. Caricain is naturally expressed as an inactive zymogen called procaricain. The inactive form of the protease contains an inhibitory proregion which consists of an additional 106 N-terminal amino acids; the proregion is removed upon activation.Results The crystal structure of procaricain has been refined to 3.2 å resolution; the final model consists of three non-crystallographically related molecules. The proregion of caricain forms a separate globular domain which binds to the C-terminal domain of mature caricain. The proregion also contains an extended polypeptide chain which runs through the substrate-binding cleft, in the opposite direction to that of the substrate, and connects to the N terminus of the mature region. The mature region does not undergo any conformational change on activation.Conclusions We conclude that the rate-limiting step in the in vitro activation of procaricain is the dissociation of the prodomain, which is then followed by proteolytic cleavage of the extended polypeptide chain of the proregion. The prodomain provides a stable scaffold which may facilitate the folding of the C-terminal lobe of procaricain

Ceramides: a new player in the inflammation-insulin resistance paradigm?

No abstract available

Nitrous oxide misuse and vitamin B12 deficiency

A 36-year-old man presented to hospital with a 5-week history of ascending limb paraesthesiae and balance difficulties. He had no medical or travel history of note, but admitted habitual nitrous oxide (N2O) inhalation. Neurological examination revealed a sensory ataxia with pseudoathetosis in the upper limbs and reduced vibration sensation to the hips bilaterally. Significant investigation results included a low serum vitamin B12 concentration, mild macrocytosis and raised serum homocysteine concentration. T2 MRI of the spinal cord demonstrated increased signal extending from C1 to T11 in keeping with a longitudinal myelitis. The patient was diagnosed with a myeloneuropathy secondary to vitamin B12 deficiency, resulting from heavy N2O inhalation. He was treated with intramuscular vitamin B12 injections and received regular physiotherapy. At discharge, he was able to mobilise short distances with the aid of a zimmer frame, and was independently mobile 8 weeks later

The mesoproterozoic Stac Fada Member, NW Scotland : an impact origin confirmed but refined

Funding to GRO from the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant program and the Canadian Space Agency (CSA) Canadian Analogue Research Network and Field Investigation programs is gratefully acknowledged. Part of LF’s work was supported by the Department of Foreign Affairs and International Trade (DFAIT), Government of Canada.The origin of the Stac Fada Member has been debated for decades with several early hypotheses being proposed, but all invoking some connection to volcanic activity. In 2008, the discovery of shocked quartz led to the hypothesis that the Stac Fada Member represents part the continuous ejecta blanket of a meteorite impact crater, the location of which was, and remains, unknown. In this paper, we confirm the presence of shock-metamorphosed and -melted material in the Stac Fada Member; however, we also show that its properties are unlike any other confirmed and well documented proximal impact ejecta deposits on Earth. Instead, the properties of the Stac Fada Member are most similar to the Onaping Formation of the Sudbury impact structure (Canada) and impact melt-bearing breccias from the Chicxulub impact structure (Mexico). We thus propose that, like the Sudbury and Chicxulub deposits, Melt Fuel Coolant Interactions – akin to what occur during phreatomagmatic volcanic eruptions – played a fundamental role in the origin of the Stac Fada Member. We conclude that these rocks are not primary impact ejecta but instead were deposited beyond the extent of the continuous ejecta blanket as high-energy ground-hugging sediment gravity flows.PostprintPeer reviewe