Coagulation factor deficiency as a cause of recurrent fetal loss: a red herring!

Whether severe coagulation factor deficiency can cause adverse pregnancy outcomes or recurrent fetal loss is not definitely known. We report here on five women with severe deficiency of coagulation factors (two factor X, one factor XI, one factor VII and one von Willebrand factor) who presented with history of unexplained fetal loss or with adverse pregnancy outcome. Detailed investigations of thrombophilia showed that four patients were positive for antiphospholipid antibodies, one of whom was also homozygous for the plasminogen-activator inhibitor-1 4G/4G polymorphism, and the fifth patient was deficient for protein C. Despite the concomitant presence of both coagulation factor defect and thrombophilia, fetal loss may be attributed to factor defect that in reality is a red herring, with underlying thrombophilia not being evaluated.     

Optimal management of adults with pharyngitis – a multi-criteria decision analysis

Background  

Current practice guidelines offer different management recommendations for adults presenting with a sore throat. The key issue is the extent to which the clinical likelihood of a Group A streptococcal infection should affect patient management decisions. To help resolve this issue, we conducted a multi-criteria decision analysis using the Analytic Hierarchy Process.     

Malassezia furfur in a case of onychomycosis: colonizer or etiologic agent?

The etiologic role of Malassezia furfur in onychomycosis is a contentious diagnostic problem because its keratinolytic ability has never been verified. This case report describes the isolation of M. furfur from the infected nails of a child clinically diagnosed with onychomycosis, and discusses the role of this organism as an etiologic agent/colonizer. The patient presented with subungual hyperkeratosis and onycholysis without associated paronychia. Budding yeast cells compatible with M. furfur were repeatedly demonstrated in KOH wet mounts of damaged nails, histopathology of hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) stained sections showed penetration of fungal elements between deeper layers of keratin, and numerous colonies of M. furfur were isolated on three consecutive occasions from nail specimens collected from different areas of hand and toenail lesions. No evidence of nail invasion by dermatophytic or nondermatophytic filamentous fungi were found by direct microscopy or culture. Microscopy and culture were negative following 12 weeks of ketoconazole treatment, which resulted in growth of healthy nail plates with normal beds. We can infer from these observations that M.furfur was an etiologic agent rather than a colonizer in the patient's nails even though direct keratinolytic character of this fungus was not demonstrated.     

最大的挑战：健康资源与财富分配不均日趋严重

今年8月18日本刊出版了第4期——以“转型中的中国医疗卫生”为主题，其中8篇文章在英国医学杂志（BMJ）同步发表。引起了读者们的兴趣与关注，特别值得注意的是国外读者在阅读BMJ后发来电子邮件表达了他们对中国医疗卫生现状与体制改进的关注以及建设性的意见，我们翻译了其中的部分来信，在本期和下期分别刊登，以飨读者。[编者按]     

Synthesis and Neuromuscular Blocking Activity of 16β-Piperidino Epiandrosterone Derivatives

This study reports the synthesis of steroidal quaternary ammonium compounds 11 and 12, with quaternary nitrogen at position 3 and 16 of the steroid nucleus in 5α-epiandrosterone series; along with their neuromuscular blocking activity using chick biventer cervicis muscle preparation. The compound 12 was found to be five times more potent than 11 in reducing twitch response to nerve stimulations, indicating the importance of extended interonium distances and 17-acetoxy function for potent antagonist activity.     

In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1‐13C] and [2‐13C]pyruvate

Hyperpolarized ¹³C MRS allows the in vivo assessment of pyruvate dehydrogenase complex (PDC) flux, which converts pyruvate to acetyl‐coenzyme A (acetyl‐CoA). [1‐¹³C]pyruvate has been used to measure changes in cardiac PDC flux, with demonstrated increase in ¹³C‐bicarbonate production after dichloroacetate (DCA) administration. With [1‐¹³C]pyruvate, the ¹³C label is released as ¹³CO₂/¹³C‐bicarbonate, and, hence, does not allow us to follow the fate of acetyl‐CoA. Pyruvate labeled in the C₂ position has been used to track the ¹³C label into the TCA (tricarboxylic acid) cycle and measure [5‐¹³C]glutamate as well as study changes in [1‐¹³C]acetylcarnitine with DCA and dobutamine. This work investigates changes in the metabolic fate of acetyl‐CoA in response to metabolic interventions of DCA‐induced increased PDC flux in the fed and fasted state, and increased cardiac workload with dobutamine in vivo in rat heart at two different pyruvate doses. DCA led to a modest increase in the ¹³C labeling of [5‐¹³C]glutamate, and a considerable increase in [1‐¹³C]acetylcarnitine and [1,3‐¹³C]acetoacetate peaks. Dobutamine resulted in an increased labeling of [2‐¹³C]lactate, [2‐¹³C]alanine and [5‐¹³C]glutamate. The change in glutamate with dobutamine was observed using a high pyruvate dose but not with a low dose. The relative changes in the different metabolic products provide information about the relationship between PDC‐mediated oxidation of pyruvate and its subsequent incorporation into the TCA cycle compared with other metabolic pathways. Using a high dose of pyruvate may provide an improved ability to observe changes in glutamate. Copyright © 2013 John Wiley & Sons, Ltd.     

Susceptibility of colistin-resistant pathogens to predatory bacteria

The increase in multidrug-resistant Gram-negative bacterial infections has forced the reintroduction of antibiotics such as colistin. However, the spread of the plasmid-borne mcr-1 colistin resistance gene have moved us closer to an era of untreatable Gram-negative infections. To evaluate whether predatory bacteria could be used as a potential therapeutic to treat this upcoming threat, the ability of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus to prey on several clinically relevant mcr-1-positive, colistin-resistant isolates was evaluated. No change in the ability of the predators to prey on free swimming and biofilms of prey cells harboring mcr-1 was measured, as compared to their mcr-1 negative strain.