Local Anesthetic−Induced Methemoglobinemia During Pregnancy: A Case Report and Evaluation of Treatment Options

Background

Methemoglobinemia is a well-recognized adverse drug reaction related to the use of certain local anesthetic agents. The mainstay of treatment for methemoglobinemia is i.v. methylene blue, along with provision of supplemental oxygen; however, methylene blue is listed as a category X teratogen. This poses an issue should methemoglobinemia develop during pregnancy.

Care planning for long‐term conditions – a concept mapping

Objective

This article focuses on approaches within clinical practice that seek to actively involve patients with long‐term conditions (LTCs) and how professionals may understand and implement them. Personalized care planning is one such approach, but its current lack of conceptual clarity might have impeded its widespread implementation to date. A variety of overlapping concepts coexist in the literature, which have the potential to impair both clinical and research agendas. The aim of this article is therefore to explore the meaning of the concept of care planning in relation to other overlapping concepts and how this translates into clinical practice implementation.

Methods

Searches were conducted in the Cochrane database for systematic reviews, CINHAL and MEDLINE. A staged approach to conducting the concept mapping was undertaken, by (i) an examination of the literature on care planning in LTCs; (ii) identification of related terms; (iii) locating reviews of those terms. Retrieved articles were subjected to a content analysis, which formed the basis of our concept maps. (iv) We then appraised these against knowledge and experience of the implementation of care planning in clinical practice.

Results and Conclusions

Thirteen articles were retrieved, in which the core importance of patient‐centredness, shared decision making and self‐management was highlighted. Literature searches on these terms retrieved a further 24 articles. Our concept mapping exercise shows that whilst there are common themes across the concepts, the differences between them reflect the context and intended outcomes within clinical practice. We argue that this clarification exercise will allow for further development of both research and clinical implementation agendas.     

Consensus-recommendations for sirolimus in liver transplantation

Sirolimus is an m-TOR inhibitor without renal side effects and potentially protects against the development of malignancy. Due to a higher incidence of complications in two trials and an official warning in the drug information, the use of Sirolimus in liver transplantation is limited. The participants of this consensus meeting had to analyse and evaluate the literature with respect to the potential role of Sirolimus in liver transplantation. This consensus statement follows the scheme normally employed for the presentation of guidelines including the grading of evidence (1a-5) and the extent of recommendation (A-C). Moreover, the consensus included the experience of the authors with respect to the handling of Sirolimus after liver transplantation.     

Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer

Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all interleukin-3-dependent cell lines tested. Murine interleukin-3- dependent Ba/F3 cells expressing the mutated but not the normal form of MPL were tumorigenic when transduced into syngeneic mice. Analysis of intracellular signaling pathways indicated that the mutant MPL protein constitutively activated two distinct signaling pathways, SHC-Raf-MAPK and JAK2-STAT3/STAT5.     

Role of copper in mitochondrial iron metabolism

Heme synthesis by copper-deficient cells was investigated to elucidate the nature of the defect in intracellular iron metabolism. Iron uptake from transferrin by copper-deficient reticulocytes was 52% of normal, and the rate of heme synthesis was 33% of normal. Hepatic mitochondria isolated from copper-deficient animals were deficient in cytochrome oxidase activity and failed to synthesize heme from ferric iron (Fe III) and protoporphyrin at the normal rate. The rate of heme synthesis correlated with the cytochrome oxidase activity. Heme synthesis from Fe(III) and protoporphyrin by normal mitochondria was enhanced by succinate and inhibited by malonate, antimycin A, azide, and cyanide. It is proposed that an intact electron transport system is required for the reduction of Fe(III), thereby providing a pool of ferrous iron (Fe II) for protoheme and heme a synthesis.     

Cloning and sequence analysis of cDNA for human cathepsin D.

An 1110-base-pair cDNA clone for human cathepsin D was obtained by screening a lambda gt10 human hepatoma G2 cDNA library with a human renin exon 3 genomic fragment. Poly(A)+ RNA blot analysis with this cathepsin D clone demonstrated a message length of about 2.2 kilobases. The partial clone was used to screen a size-selected human kidney cDNA library, from which two cathepsin D recombinant plasmids with inserts of about 2200 and 2150 base pairs were obtained. The nucleotide sequences of these clones and of the lambda gt10 clone were determined. The amino acid sequence predicted from the cDNA sequence shows that human cathepsin D consists of 412 amino acids with 20 and 44 amino acids in a pre- and a prosegment, respectively. The mature protein region shows 87% amino acid identity with porcine cathepsin D but differs in having nine additional amino acids. Two of these are at the COOH terminus; the other seven are positioned between the previously determined junction for the light and heavy chains of porcine cathepsin D. A high degree of sequence homology was observed between human cathepsin D and other aspartyl proteases, suggesting a conservation of three-dimensional structure in this family of proteins.