Apolipoprotein D is down-regulated during malignant transformation of neurofibromas

Apolipoprotein D (apoD) expression was studied in nonneoplastic peripheral nerve, neurofibromas (NFs), and malignant peripheral nerve sheath tumors (MPNSTs) by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. Multiplex quantitative polymerase chain reaction for messenger RNA was performed on a series of formalin-fixed and paraffin-embedded specimens that included 9 MPNSTs, 12 NFs, and 4 normal peripheral nerves. The average apoD expression was 108-fold decreased (DeltaCt = -7.3) in the MPNSTs compared with the NFs (P < .05). ApoD expression levels were 3.0-fold elevated (DeltaCt = 1.7) in the NFs compared with nonneoplastic peripheral nerve (P < .05). In situ hybridization for apoD RNA was performed on a separate series of 10 cases in which each microscopic section included both MPNST and the NF from which it arose. These studies confirmed elevated apoD expression in NFs compared with MPNSTs and demonstrated that this expression was variable among individual cells within the NFs. Differential expression by immunohistochemistry could only be demonstrated in selected areas, most likely because apoD protein is a small molecule that is secreted out of the cell into the extracellular space and plasma. ApoD expression initially increases a small amount with the formation of NFs from nonneoplastic peripheral nerve and subsequently decreases markedly as NFs transform into MPNSTs. This expression pattern may serve as a marker for cell cycle inhibition during peripheral nerve tumorigenesis.     

Antimicrobial use and outcomes in patients with multidrug-resistant and pansusceptible Salmonella Newport infections, 2002-2003

Multidrug-resistant Salmonella Newport with decreased susceptibility to ceftriaxone (MDR-AmpC) is becoming increasingly common in its food animal reservoirs and in humans. Few data exist on rates of antimicrobial use or differences in clinical outcomes in persons infected with MDR-AmpC or other Salmonella strains. We conducted a case-comparison analysis of data from a multistate population-based case-control study to identify antimicrobial treatment choices and differences in clinical outcomes in those infected with MDRAmpC compared to pansusceptible S. Newport. Of isolates from 215 laboratory-confirmed S. Newport cases, 54 (25%) were MDR-AmpC, 146 (68%) were pansusceptible, and 15 (7%) had other resistance patterns; 146 (68%) patients with S. Newport were treated with antimicrobial agents and 66 (33%) were hospitalized. Over two-thirds of cases at low-risk for serious complications received antimicrobial therapy, most commonly with fluoroquinolones, to which this strain was susceptible. There were no significant differences in symptoms, hospitalization, duration of illness, or other outcomes between the persons infected with MDR-AmpC and pansusceptible S. Newport. Although currently prevalent MDR-AmpC S. Newport strains remains susceptible to the antimicrobial most commonly prescribed for it, continued efforts to reduce unnecessary use of antimicrobial agents in food animals and humans are critical to prevent further development of resistance to quinolones and cephalosporins, which is likely to lead to substantial adverse outcomes.     

Who supports the support workers? Cross-sectional survey of support workers' experience and views

Support groups provide information and emotional support to families. Despite a recent growth in the number and size of these groups, there are no formal structures in place to provide support for the support worker. We performed a cross-sectional survey using a self-completion postal questionnaire, with the aim of identifying the structure, training needs and support given to workers. The participants were support workers from 112 United Kingdom-based organisations listed on the 'Contact a Family' website (www.cafamily.co.uk). We received 104 replies from 50/112 organisations (44%). Of these, 94/104 (90%) worked from home as volunteers. Two-thirds, 69/104, admitted times when they struggled to cope. A total of 43 (41%) admitted occasions of concern over the care given by a client to their affected relative. No group employed a professional to act in a clinical supervisory role. Our study suggests that support workers are highly committed to their role; these workers need support to ensure that they give appropriate advice under difficult circumstances.     

Increasing transplant mass results in long-term allograft survival and recovery from transplant vasculopathy

Late allograft rejection due to transplant vasculopathy continues to be a major clinical problem. Increasing the ratio of donor transplant size to recipient weight has been shown to reduce the incidence of late allograft failure. Using a murine pancreas transplant model we have tested the hypothesis that increasing the donor transplant size in a recipient can promote long-term allograft survival by promoting recovery from transplant vasculopathy. Recipients of an allograft that showed extensive vasculopathy were transplanted with a second donor transplant. The effect of the second allograft on the vasculopathy present in the first graft was measured. Transplanting a second allograft reversed all signs of ongoing rejection, including transplant vasculopathy, resulting in long-term survival of the first graft. Vasculopathy was only reversed if the first and second grafts were from the same mouse strain, suggesting an antigen-specific mechanism. However, the recovery of the first graft was not associated with antigen-specific peripheral tolerance.     

Report of the symposium

Summary The past decades have seen considerable shifts of emphasis in surgical care. The recognition that pus was not laudable, was followed by a realisation that not all complications were inevitable and that prophylaxis could effectively reduce the incidence of most common problems in the post-operative period. As anaesthesia has become safer, it has been possible to embark on more intricate and prolonged procedures and for sufficient time to be available to ensure adequate intraoperative care.These two phenomena have firstly increased the complexity of management in the post-operative period, and have brought this aspect of surgical care more obviously to the limelight. However, many separate disciplines are involved in the care of the patient post-operatively, and the Symposium was organised¹ to bring the different groups together to identify the areas of recent development in the different specialities and to integrate the overall care of the individual patient.Abbreviations ARDS adult respiratory distress syndrome - DIC disseminated intravascular clotting     

Tropic effects of otic epithelium on cochleo-vestibular ganglion fiber growth in vitro

Sensory nerve fibers of the cochleo-vestibular ganglion (CVG) innervate the otic epithelium in the early chick embryo by directed growth. To see if the target tissue could exert a tropic influence, we co-cultured CVGs from chick embryos (Hamburger-Hamilton stages 16–30) in a 3D collagen matrix with their normal target epithelium or with other epithelial tissues taken from the same or different stages of development. The pattern of neurite outgrowth and the viability of the CVG after five days in vitro were assessed histologically with a silver method. On the basis of the patterns of neurite outgrowth directed toward the epithelium the cultures were classified as having slightly, mostly, exclusively, or no directed outgrowth. Of 49 cultures containing otic epithelium, 33 had mostly or exclusively directed growth patterns. This effect did not depend on any particular stage difference between co-cultures or on their viability in vitro. Cultures of non-sensory otic epithelium (endolymphatic duct) also presented directed growth patterns. Co-cultures with ectoderm from forelimb or visceral arch had little, if any, directed growth. The directed growth could not be explained simply as a result of guidance by non-neuronal cells or of the viability of the explants. The results are consistent with the hypothesis that the otic epithelium provides a tropic factor that attracts growing CVG fibers.     

Effect of age on the accumulation of lung protein following unilateral pneumonectomy in rats

The effects of unilateral pneumonectomy (PNX) on the net synthesis of right lung protein were investigated in vivo using three groups of rats with body weights (BW) ranging from 85 to 330 g. These data were compared to those from sham-operated and normal growing control animals. After PNX, both the 2-day lag prior to the compensatory increase in right lung mass (LW) and the subsequent rate of increase in LW and LW/BW ratio were independent of two-fold differences in the basal rate of lung growth. In all PNX groups, both right LW and LW/BW reached control values for both lungs, but in the older rats the time required for complete compensation was extended from 5 days to 12 days. The rate of net accumulation of right lung protein increased two-fold in the youngest PNX rats and 6 to 8-fold in the older animals, but when these changes were normalized to the protein content of the remaining tissue, the older rats appeared to respond to PNX less efficiently. Increased tissue levels of RNA and the resulting increased capacity of the lungs for protein synthesis could account for the accelerated rate of gain in right lung protein following PNX in both adult and young animals.     

Stratification based on language-related endophenotypes in autism: attempt to replicate reported linkage.

The identification of autism susceptibility genes has been hampered by phenotypic heterogeneity of autism, among other factors. However, the use of endophenotypes has shown preliminary success in reducing heterogeneity and identifying potential autism-related susceptibility regions. To further explore the utility of using language-related endophenotypes, we performed linkage analysis on multiplex autism families stratified according to delayed expressive speech and also assessed the extent to which parental phenotype information would aid in identifying regions of linkage. A whole genome scan using a multipoint non-parametric linkage approach was performed in 133 families, stratifying the sample by phrase speech delay and word delay (WD). None of the regions reached suggested genome-wide or replication significance thresholds. However, several loci on chromosomes 1, 2, 4, 6, 7, 8, 9, 10, 12, 15, and 19 yielded nominally higher linkage signals in the delayed groups. The results did not support reported linkage findings for loci on chromosomes 7 or 13 that were a result of stratification based on the language delay endophenotype. In addition, inclusion of information on parental history of language delay did not appreciably affect the linkage results. The nominal increase in NPL scores across several regions using language delay endophenotypes for stratification suggests that this strategy may be useful in attenuating heterogeneity. However, the inconsistencies in regions identified across studies highlight the importance of increasing sample sizes to provide adequate power to test replications in independent samples.     

Health seeking behavior by families of children suspected to have malaria in Kabale: Uganda

Background

Malaria is common among communities of Kabale district, and many young children die of the illness. Despite a good distribution of health facilities, able to handle malaria patients, families and individuals tend to depend on self-treatment, or private clinics where drugs used may be of doubtful quality. This study reports on health seeking behaviour by families with children suspected to have malaria.

Methodology

A community-based, cross-sectional survey among 209 rural peasant families living in 12 villages, chosen from the 5 most malaria-affected sub-counties was done. Using a questionnaire, respondents'' reactions to the disease and what decisions they took were recorded. Reasons for choices such as drugs used, location of treatment and malaria control methods were recorded.

Results

Ninety seven percent lived within easy reach of a public health facility. Over 2/3 knew how malaria was transmitted and how it presented. They believed it was best treated at public heath facilities using western type of medicine. Fifty percent of the children, who attended public health units, were treated within 24 of illness. Thirty eight percent of the caretakers knew how to correctly use chloroquine. The caretakers relied on fever, vomiting and refusal to feed as the main symptoms for their diagnosis of malaria. Only 31% of the families sought treatment from government health facilities.Fifty three percent of the families sought treatment from drug shops/vendors. Unfortunately only 38% of the families knew the correct regimen of chloroquine, 4.3% for sulpha-doxine pyrimethamine and 0.5% for quinine. One quarter could afford malaria treatment, and one out of five missed treatment because of poverty. Concerning prevention, 90% stated at least one method but only 21.2% used them.

Conclusions

Despite reasonable knowledge for diagnosis of malaria, awareness of correct treatment is limited. Paradoxically government health units appear to play a minor role in the treatment of malaria.