Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease

Human respiratory syncytial virus (RSV) is the most important cause of severe lower respiratory tract disease (LRTD) in young children worldwide. Extensive neutrophil accumulation in the lungs and occlusion of small airways by DNA‐rich mucus plugs are characteristic features of severe RSV–LRTD. Activated neutrophils can release neutrophil extracellular traps (NETs), extracellular networks of DNA covered with antimicrobial proteins, as part of the first‐line defence against pathogens. NETs can trap and eliminate microbes; however, abundant NET formation may also contribute to airway occlusion. In this study, we investigated whether NETs are induced by RSV and explored their potential anti‐viral effect in vitro. Second, we studied NET formation in vivo during severe RSV–LRTD in infants and bovine RSV–LRTD in calves, by examining bronchoalveolar lavage fluid and lung tissue sections, respectively. NETs were visualized in lung cytology and tissue samples by DNA and immunostaining, using antibodies against citrullinated histone H3, elastase and myeloperoxidase. RSV was able to induce NET formation by human neutrophils in vitro. Furthermore, NETs were able to capture RSV, thereby precluding binding of viral particles to target cells and preventing infection. Evidence for the formation of NETs in the airways and lungs was confirmed in children with severe RSV–LRTD. Detailed histopathological examination of calves with RSV–LRTD showed extensive NET formation in dense plugs occluding the airways, either with or without captured viral antigen. Together, these results suggest that, although NETs trap viral particles, their exaggerated formation during severe RSV–LRTD contributes to airway obstruction. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

H4 acetylation, XIST RNA and replication timing are coincident and define x;autosome boundaries in two abnormal X chromosomes

The inactive X (Xi) differs from its active homologue (Xa) in a number of ways, including increased methylation of CpG islands, replication late in S phase, underacetylation of histone H4 and association with XIST RNA. Global changes in DNA methylation occur relatively late in development, but the other properties all change during or shortly after the establishment of Xi and may play a role in the mechanism by which an inactive chromatin conformation spreads across most of the chromosome. In the present report, we use two human X;autosome translocation chromosomes to study the spreading of inactive X chromatin across X;autosome boundaries. In one of these chromosomes, t(X;6), Xp distal to p11.2 is replaced by 6p21.1-6pter and, in the other, ins(X;16), a small fragment derived from 16p13 is inserted into the distal third of Xq. In lymphoid cells from patients carrying these translocations in an unbalanced form, Xi was shown by HUMARA assay to be derived exclusively [t(X:6)] or predominantly [ins (X;16)] from the derived X chromosome. We used a combination of immunolabelling and RNA/DNA fluorescence in situ hybridization to define the distribution of XIST RNA, deacetylated H4 and late-replicating DNA across the two derived X chromosomes in inactive form. Within the limits of the cytogenetic techniques employed, the results show complete coincidence of these three parameters, with all three being excluded from the autosomal component of the derived X chromosome.      

Response to oral β-carotene supplementation in patients with cystic fibrosis: a 16-month follow-up study

The aim of this study was to determine the efficacy of long-term oral β -carotene supplementation for correcting impaired β -carotene status in cystic fibrosis patients. Thirty-five patients (2.3-30.5 years of age) with coefficients of fat absorption of 46-96% (median 88%) received β -carotene 0.5 mg/kg daily and were followed over a 16-month treatment period. Baseline plasma β -carotene concentrations in patients (meanSD, 0.090.06 μ mol/1) were significantly lower than those of age-matched controls (0.860.56 μ mol/1) ( p < 0.0001). Concentrations increased rapidly and reached a plateau at or before 3 weeks that was maintained throughout the study period. Values obtained at 3 weeks (0.890.64 μ mol/1) were significantly higher ( p < 0.0001) than those at baseline and did not differ from controls. Plasma retinol and α -tocopherol concentrations increased during the observation period, but remained within normal ranges. Plasma retinyl palmitate, which was below the detection limit in all but one patient at baseline, did not increase. Thus oral β -carotene supplementation is effective and normalizes β -carotene status of cystic fibrosis patients without evidence of significant side effects. β -Carotene, cystic fibrosis, LDL-cholesterol, oral supplementation, retinol, α-tocopherol     

Malignant granular cell tumour of the sciatic nerve

A case of malignant granular cell tumour of the sciatic nerve is presented. Computed tomography demonstrated iso-density with muscle and minimal enhancement. Magnetic resonance demonstrated T1 isointensity with muscle with marked enhancement, and isointensity with fat on proton and T2 images. Pathological evidence is presented for its probable Schwann cell histogenesis.     

Clinical incidence of lymphoedema in breast cancer patients in Jönköping County, Sweden

The clinical incidence of lymphoedema of the arm in breast cancer patients was studied before and after general mammography screening in the country of jönköping, Sweden. There was a significant decrease of incidence of lymphoedema from 15% in 1983 to 8% in 1988. Clinical and pathological therapy data have been analysed in relation to lymphoedema. Significant factors contributing to lymphoedema were the number of lymph nodes examined and the number of pathologically positive lymph nodes. A higher proportion of patients receiving post-operative radiotherapy to the axilla developed lymphoedema, compared with those with surgery alone.
A comparison between the two groups is impossible due to the fact that post-operative radiotherapy was prescribed only to patients with pathologically positive lymph nodes.     

Observing decision‐making in the general practice consultation: who makes which decisions?

OBJECTIVE: To investigate opportunities for, and types of decision making in the general practice (primary care) consultation, and examine differences in skills of those doctors who are successful at meeting their patients' preferences and those who are less successful. DESIGN: Observation study of doctor-patient consultations in general practice. PARTICIPANTS: Patients attending for routine appointments in 12 general practice surgeries across Oxfordshire. METHODS: A total of 212 doctor-patient consultations were video-recorded. The patients involved completed a questionnaire to elicit their perceptions of how decisions were made. The video-taped recordings were coded with a new instrument, the Evidence Based Patient Choice Instrument (EBPCI), to classify the number and type of decision-making opportunities arising during each consultation. A total of 149 recordings were coded using the Oxbridge Rating Scale to assess the doctors' consultation styles. RESULTS: There was a range of decision-making opportunities in addition to those involving medical treatment. With the exception of 'fitness for work', decisions were generally 'doctor led'. There was only moderate agreement between patient perceptions of their level of involvement in decision making and the objective ratings using the EBPCI. There was wide variation in the ability of doctors to meet their patients' preferences for involvement. CONCLUSIONS: There are many decisions made in primary care consultations, in addition to those about medical treatments, in which patients could be involved to a greater extent than they currently are. Some doctors are significantly better than others at meeting different patients' preferences for their decision-making role. Patients' perceptions of shared decision making appears to be influenced by the doctors' general consultation skills.     

Elevated Serum Alpha Fetoprotein and Normal Liquor Alpha Fetoprotein Values in Association with an Abdominal Pregnancy

Summary: A case report is described in which abdominal pregnancy was misdiagnosed by ultrasound scanning as a pregnancy within a horn of a bicornuate uterus. Two serum alpha fetoprotein (SAFP) results were greatly elevated and an amniocentesis was performed, the liquor alpha fetoprotein (LAFP) and karyotype were normal. Elective Caesarean section was performed at 38 weeks for a persistent transverse lie and an abdominal pregnancy was found. The outcome was excellent for both the mother and child.
This is the first reported case of amniocentesis and measurement of LAFP in an abdominal pregnancy and confirms abdominal pregnancy as a rare cause of an elevated SAFP.     

Screening for a raised rectal temperature in Africa

The main purpose of this study was to compare rectal and axillary temperature measurements in African children. Altogether 573 sick children were seen in an outpatient setting in rural West Africa. Rectal and axillary temperatures were measured and the parent or guardian was asked if they thought that the child had a raised body temperature. Normal ranges were defined from an age matched population of 203 healthy children. A raised axillary temperature predicted a raised rectal temperature with a sensitivity of 98% and a specificity of 88%. The parents' impression that their child had a fever was a less sensitive (89%) and less specific (59%) indicator of raised rectal temperature. A raised axillary temperature is a good screening test for a raised rectal temperature in African children.     

Fibromatosis of bone in children

Radiographs, computed tomograms, and radionuclide bone scans were obtained preoperatively in three children with fibromatosis involving the bones and soft tissues of the extremities. Two of the children had identical scar-like bone lesions of the proximal tibia, which, to the authors' knowledge, have not been reported before in this disease. The lesions recurred in two children.