Személyre szabott kezelés szinkrón, nyirokcsomó-pozitív petefészek- és vastagbéldaganatban

Absztrakt A 71 éves nőbetegnél jobb alhasi fájdalom és láz miatt sürgősségi laparotomiára került sor. Makroszkóposan duplex coecum és colon transversum, továbbá szigma/bal petefészek daganatának gyanúja merült fel. A szövettani vizsgálat szinkrón bal petefészek- (papillaris adenocarcinoma) és colon transversum (tubularis adenocarcinoma) daganatot mutatott. Mind a két primer daganat a regionális nyirokcsomóikba adott áttétet, továbbá a petefészek-daganat infiltrálta a szigmabelet és távoli áttétet képzett a coecum területére. Immunhisztokémiával a nyirokcsomóáttétek egyértelműen elkülöníthetők voltak: petefészek-eredetű CK7-pozitív, coloneredetű CK20- és CEA-pozitív. A szikrón primer daganatokat kombinált kemoterápiával kezeltük (FOLFOX-4 és heti paclitaxel). A kombinált kezelést a beteg jól tolerálta. A ritka eset hangsúlyozza annak jelentőségét, hogy a többszörös primer daganatok egyénre szabott kemoterápiás sémával kezelhetők jó hatásfokkal és enyhe mellékhatásokkal. Orv. Hetil., 2015, 156(23), 939–943

Hemophagocytic lymphohistiocytosis secondary to infections:a tertiary care experience

Background: Hemophagocytic lymphohistiocytosis is an uncommon complication of various conditions. It is characterized by immune dysregulation and massive cytokine release causing multiorgan dysfunction. It is classified as primary and secondary to various etiologies like infections, malignancies and autoimmune disease. As it has high mortality, clinician awareness is important for early diagnosis and improved outcome. Aim of the study was to study the etiologies, clinical manifestations, complications and laboratory features in patients diagnosed with infection associated hemophagocytic syndrome (IAHS).Methods: We have done retrospective analysis of all cases diagnosed to have Infection Associated Hemophagocytic Syndrome (IAHS) between March 2012 to November 2015 in a 1000 bedded tertiary care hospital in south India.Results: Total five cases detected. Most of the cases are related to tropical infections (80%). All of them presented with fever, cytopenias and organomegaly. Ferritin and Triglycerides were elevated in all patients. Bone marrow hemophagocytosis was observed in 80% of cases. Diagnostic protocol of HLH 2004 was followed. Only 20% survival observed.Conclusions: IAHS is a rare fulminant complication associated with diagnostic and therapeutic challenges because of overlapping clinical features with sepsis. Increased physician awareness, early diagnosis and therapeutic interventions may improve survival

Structural basis for antibiotic transport and inhibition in PepT2

The uptake and elimination of beta-lactam antibiotics in the human body are facilitated by the proton-coupled peptide transporters PepT1 (SLC15A1) and PepT2 (SLC15A2). The mechanism by which SLC15 family transporters recognize and discriminate between different drug classes and dietary peptides remains unclear, hampering efforts to improve antibiotic pharmacokinetics through targeted drug design and delivery. Here, we present cryo-EM structures of the proton-coupled peptide transporter, PepT2 from Rattus norvegicus, in complex with the widely used beta-lactam antibiotics cefadroxil, amoxicillin and cloxacillin. Our structures, combined with pharmacophore mapping, molecular dynamics simulations and biochemical assays, establish the mechanism of beta-lactam antibiotic recognition and the important role of protonation in drug binding and transport

Caractérisation des sables et morphologie du fond du lac du barrage hydroélectrique de Taabo (Côte d\'Ivoire)

Une analyse sédimentologique et minéralogique réalisée sur un cycle hydrologique entre octobre 2004 et août 2005 a permis d\'évaluer les charges solides en suspension et de caractériser les sédiments du lac du barrage de Taabo. La concentration moyenne en matières en suspension (12 mg.L-1) et la turbidité moyenne (20 NTU) montrent que les eaux du lac sont relativement peu chargées. Ces charges en suspension sont composées d\'une fraction inorganique et d\'une fraction organique. Les sables qui composent les sédiments de ce lac sont majoritairement moyens à grossiers et médiocrement classés avec une moyenne granulométrique de 451,48 μm et un indice de classement moyen de 1,13. Les vases et les sables fins occupent les zones profondes du lac et les zones envahies par les végétaux aquatiques. Les sables moyens sont localisés aux voisinages des berges tandis que les sables grossiers sont situés aux voisinages des îles et de la digue. Le cortège minéralogique des sédiments est caractérisé de minéraux lourds (l\'amphibole, la tourmaline, le diopside et l\'épidote) et de minéraux légers (le quartz et les feldspaths). Par ailleurs, cette étude a permis de réaliser la première carte bathymétrique du lac de Taabo 26 ans après sa mise en eau.A sedimentological and mineralogical study carried out on a hydrological cycle from October 2004 to August 2005 has permitted to assess the solid suspended matters and to characterize the sediments of the Taabo dam lake. The average of suspended matters concentration (12 mg.L -1) and the average of turbidity (20 NTU) reveal that the lake is relatively little loaded with suspended matters. These suspended matters are compound of an inorganic fraction and an organic fraction. Sands size in the sediments of this lake are from middle to coarse and badly classified. The grain size average is 451,48 μm; the standard deviation average is 1,13. Muds and fine sands are found in the deeper zones of the lake and also in the zones invaded by the aquatic plants. Middle sands are located near banks while coarse sands are located aside the islands and the dam. The minerals found in the sediments are characterized by heavy minerals (the amphibole, tourmaline, diopside and epidote) and light minerals (quartz and feldspars). Elsewhere, this study has permitted to carry out the first bathymetric Map of this lake 26 years after its setting in water. Keywords: keywordBarrage, lac, granulométrie, minéralogie, bathymétrie, Taabo./Dam, lake, grain size, mineralogy, bathymetry, Taabo.Sciences & Nature Vol. 4 (1) 2007: pp. 93-10

Interactions between Australian cancer physicians and the pharmaceutical industry: a qualitative study

OBJECTIVES: To understand how and why Australian cancer physicians interact with the pharmaceutical industry. DESIGN: Qualitative study using semistructured interviews, performed by a medical oncologist. Thematic analysis using a combination of deductive and inductive codes. SETTING: Given the evidence on industry influences on clinical practice and the importance to the market of oncology drugs, we sought to better understand cancer physicians' experiences. Practising consultant medical oncologists and clinical haematologists from four Australian states were interviewed over Zoom. PARTICIPANTS: 16 cancer physicians were interviewed between November 2021 and March 2022, from 37 invited (response rate 43%). Most were medical oncologists (n=12 of 16, 75%) and male (n=9 of 16, 56%). OUTCOME MEASURES: The analysis of all interviews was based on grounded theory. Transcripts were coded and then codes formed into themes with supporting quotes. The themes were then placed into categories, used to describe the broad areas into which the themes could be grouped. RESULTS: Six themes were identified that fell within two broad categories: cancer physicians' views and experiences of interactions and management of these interactions. Views and experiences included: the transactional nature of relationships, risks of research dependence, ethical challenges and varied attitudes based on interaction type. Management themes included: lack of useful guidance and reduced interactions during the COVID-19 pandemic. These led to an overarching seventh theme, on the desire for a 'middle road'. Cancer physicians identified the transactional nature of industry relationships and felt uncomfortable with several types of interactions, including those with sales representatives. Most wanted less contact with industry, and the forced separation that occurred with the COVID-19 pandemic was generally welcome. CONCLUSIONS: Cancer physicians may have difficulty balancing the perceived need to interact with industry in modern cancer care while maintaining distance to minimise conflicts of interest. Further research is needed to assess management strategies in this area

A signal sequence suppressor mutant that stabilizes an assembled state of the twin arginine translocase

The twin-arginine protein translocation (Tat) system mediates transport of folded proteins across the cytoplasmic membrane of bacteria and the thylakoid membrane of chloroplasts. The Tat system of Escherichia coli is made up of TatA, TatB and TatC components. TatBC comprise the substrate receptor complex, and active Tat translocases are formed by the substrate-induced association of TatA oligomers with this receptor. Proteins are targeted to TatBC by signal peptides containing an essential pair of arginine residues. We isolated substitutions, locating to the transmembrane helix of TatB that restored transport activity to Tat signal peptides with inactivating twin arginine substitutions. A subset of these variants also suppressed inactivating substitutions in the signal peptide binding site on TatC. The suppressors did not function by restoring detectable signal peptide binding to the TatBC complex. Instead, site specific crosslinking experiments indicate that the suppressor substitutions induce conformational change in the complex and movement of the TatB subunit. The TatB F13Y substitution was associated with the strongest suppressing activity, even allowing transport of a Tat substrate lacking a signal peptide. In vivo analysis using a TatA-YFP fusion showed that the TatB F13Y substitution resulted in signal peptide independent assembly of the Tat translocase. We conclude that Tat signal peptides play roles in substrate targeting and in triggering assembly of the active translocase