Withdrawing medical treatment: implications of the Bland case.

The question of whether it is possible to withdraw a feeding system from a patient who is in a persistent vegetative state raises serious legal and ethical issues which have recently been discussed in the High Court. This article discusses the issues and the Court's conclusions in this particular case.     

Multiple cis-regulatory elements and the yeast sulphur regulatory network are required for the regulation of the yeast glutathione transporter, Hgt1p

HGT1 encodes a high-affinity glutathione transporter in the yeast Saccharomyces cerevisiae that is induced under sulphur limitation. The present work demonstrates that repression by organic sulphur sources is under the control of the classic sulphur regulatory network, as seen by the absence of expression in a met4 background. Cysteine appeared to be the principal regulatory molecule, since elevated levels were seen in str4 strains (deficient in cysteine biosynthesis) that could be repressed by elevated levels of cysteine, but not by methionine or glutathione. Investigations into cis-regulatory elements revealed that the previously described motif, a 9-bp cis element, CCGCCACAC, located at the –356 to –364 region of the promoter could in fact be refined to a 7-bp CGCCACA motif that is also repeated at –333 to –340. The second copy of this motif was essential for activity, since mutations in the core region of the second copy completely abolished activity and regulation by sulphur sources. Activity, but not regulation, could be restored by reintroducing an additional copy upstream of the first copy. A third region, GCCGTCTGCAAGGCA, conserved in the HGT1 promoters of the different Saccharomyces spp, was observed at –300 to –285 but, while mutations in this region did not lead to any loss in repression, the basal and induced levels were significantly increased. In contrast to a previous report, no evidence was found for regulation by the VDE endonuclease. The strong repression at the transport level by glutathione seen in strains overexpressing HGT1 was due to a glutathione-dependent toxicity in these cells.     

Infection with an extended-spectrum beta-lactamase-producing strain of Serratia marcescens following tongue reconstruction

We report a case of postsurgical wound infection of polymicrobial etiology caused by Serratia marcescens and Pseudomonas aeruginosa following the use of a radial forearm free flap for oncological tongue reconstruction. S. marcescens was a producer of SHV-12 extended-spectrum beta-lactamase (ESBL). This is the first report from India of this ESBL. S. marcescens and P. aeruginosa were resistant to the empirical perioperative antibiotics administered. Delay in the recognition of the type of infection and in the institution of appropriate therapy resulted in total loss of the free flap.     

The association of childhood asthma with mental health and developmental comorbidities in low-income families

Objective: The objective of the study was to determine the relationship of childhood asthma with mental health and developmental indicators in low-income families. Methods: Parents/guardians of approximately 400 children, aged 2–14 years, were recruited from a charity hospital serving low income neighborhoods in the outskirts of Karachi, Pakistan. Mothers of children were interviewed in their local language by a trained nurse. Eight self-reported comorbidities were grouped into two constructs based on factor analysis and conveniently labeled as mental health (anxiety, attention and behavioral problems) and developmental problems (learning, developmental delay, hearing impairment, sleep and speech problems). Data were analyzed using multiple logistic regression, adjusted for age, sex, presence of older siblings, number of people in the household, child birth weight, presence of mold, and family history of asthma or hay fever. Results: Children with asthma had 18 times greater odds of mental health problems (adjusted OR?=?18.0, 95% CI: 9.2, 35.1) as compared to children without asthma. The odds of developmental problems were more than 14 times greater for children with asthma (adjusted OR?=?14.3, 95% CI: 7.8, 26.1) as compared to children without asthma. Conclusions: This study found mental and developmental adverse consequences of childhood asthma in low-income families. Identifying and treating asthma at an early age could reduce the burden of comorbidities in this population.     

Clarifying values: an updated review

Background

Consensus guidelines have recommended that decision aids include a process for helping patients clarify their values. We sought to examine the theoretical and empirical evidence related to the use of values clarification methods in patient decision aids.

Methods

Building on the International Patient Decision Aid Standards (IPDAS) Collaboration’s 2005 review of values clarification methods in decision aids, we convened a multi-disciplinary expert group to examine key definitions, decision-making process theories, and empirical evidence about the effects of values clarification methods in decision aids. To summarize the current state of theory and evidence about the role of values clarification methods in decision aids, we undertook a process of evidence review and summary.

Results

Values clarification methods (VCMs) are best defined as methods to help patients think about the desirability of options or attributes of options within a specific decision context, in order to identify which option he/she prefers. Several decision making process theories were identified that can inform the design of values clarification methods, but no single “best” practice for how such methods should be constructed was determined. Our evidence review found that existing VCMs were used for a variety of different decisions, rarely referenced underlying theory for their design, but generally were well described in regard to their development process. Listing the pros and cons of a decision was the most common method used. The 13 trials that compared decision support with or without VCMs reached mixed results: some found that VCMs improved some decision-making processes, while others found no effect.

Conclusions

Values clarification methods may improve decision-making processes and potentially more distal outcomes. However, the small number of evaluations of VCMs and, where evaluations exist, the heterogeneity in outcome measures makes it difficult to determine their overall effectiveness or the specific characteristics that increase effectiveness.

     

Outbreak of Streptococcus pyogenes emm type 58 in a high dependency unit of a level-1 trauma center of India

Background and Aims:

Group A Streptococcus (GAS) can cause illnesses ranging from self-limited to severe, life-threatening, invasive infections. The objective of the following study was to investigate a suspected Streptococcus pyogenes outbreak in a high dependency unit (HDU) of our trauma center.

Materials and Methods:

All the isolates of beta hemolytic Streptococci were identified by standard microbiological methods, Vitek 2 system and latex agglutination tests. Antimicrobial susceptibility testing was performed as recommended by Clinical Laboratory Standards Institute. Exotoxin genes, including speA, speB, speC, speF, smeZ, ssa, speG, speH, speJ, speL, speM and speI were detected by polymerase chain reaction (PCR). The emm types of isolates of S. pyogenes were determined by sequencing the variable 5’ end of emm gene after amplification by PCR.

Results:

In a 28 bedded poly-trauma ward with a four bedded HDU three out of four patients developed S. pyogenes emm type 58 infection. The strain was macrolide and tetracycline resistant and produced the Streptococcal pyrogenic exotoxins speB, speC, speG, speF and smeZ. Surveillance sampling was done for investigation from patients, health-care workers and environmental samples.

Conclusion:

An outbreak of GAS infections was established caused by the uncommonly reported emm type 58. The outbreak was controlled by prompt treatment, intensive surveillance, feedback and training.     

Expression of an anti‐RNA autoantibody in a mouse model of SLE increases neutrophil and monocyte numbers as well as IFN‐I expression

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of antinucleic acid autoantibodies, high levels of circulating type I interferon (IFN‐I), and an IFN‐I‐dependent elevated expression of activating FcγR. Increases in neutrophils and monocytes are often observed in clinical SLE, but how these contribute to autoantibody and IFN‐I production is poorly understood. Here, we analyzed SLE pathogenesis in 564Igi mice, an SLE‐model strain carrying gene‐targeted heavy and light chain antibody genes encoding an anti‐RNA autoantibody in a C57BL/6 background. Similar to human SLE patients, 564Igi mice produce anti‐RNA autoantibodies and expanded neutrophil and monocyte populations. These myeloid cells produced IFN‐I and exhibit increased FcγRIV expression induced via an IFN‐I autocrine loop. A direct effect of IFN‐I on 564Igi BM B cells and neutrophils was supported by their upregulation of “IFN‐I signature genes”. In addition, 564Igi developing B cells showed upregulated TLR7 resulting in IgG2a/2b class switch recombination and autoantibody production. Our results indicate that the production of anti‐RNA autoantibody is sufficient to induce an increase of BM, blood, and spleen IFN‐I‐producing neutrophils, and suggest a mechanism by which autoantibody and IFN‐I contribute to SLE by activating B lymphocytes, neutrophils, and monocyte effector cells in vivo.