Silicone granuloma from ruptured breast implants as a cause of cervical lymphadenopathy.

A 56-year-old woman with a 10-year history of bilateral silicone breast implants presented to the ear, nose and throat outpatient clinic with a 2-month history of a right-sided neck lump. She was found to have a 1.3cm supraclavicular lymph node that gave the clinical impression of being reactive. Ultrasonography guided fine needle aspiration was inconclusive and initial review of subsequent computed tomography failed to identify a cause. This was followed by excisional biopsy of the lymph node, which revealed a silicone granuloma that was linked to a ruptured right-sided breast implant placed ten years previously. This case highlights the importance for otolaryngologists to consider silicone granuloma among the differential diagnoses of cervical lymphadenopathy in patients with a history of silicone breast implants. Recognising this differential diagnosis could avoid undue anxiety for patient and clinician regarding more serious pathology.

Morphological consequences of lateral outfracture of the inferior turbinate.

OBJECTIVE: We report three cases of lateral outfracture of the inferior turbinate, which demonstrate a range of changes in the size, position and shape of the inferior turbinate. METHOD: During a study of the validity of computer modelling of nasal airflow, computed tomography scans of the noses of patients who had undergone lateral outfracture of the inferior turbinate were collected. The pre-operative scan was compared with the post-operative scan six weeks later. RESULTS: In one patient, there was only a small lateral displacement of the inferior turbinate. In the other two cases, appreciable reduction in the volume of one inferior turbinate was noted, in addition to minor changes in the shape. CONCLUSION: Lateral outfracture of the inferior turbinate produces varied and inconsistent changes in morphology which may affect the shape, size and position of the turbinate.

MR angiography and imaging for the evaluation of middle cerebral artery atherosclerotic disease.

Intracranial atherosclerotic disease may constitute the most common cause of ischemic stroke worldwide; yet, in the developed world, imaging research has largely focused on extracranial atherosclerosis. Many studies in populations of Asian, African, and Hispanic descent demonstrate the preponderance of intracranial stenosis compared with carotid stenosis. This review examines the clinical presentations of MCA atherosclerosis and stenosis and the use of noninvasive MR imaging in the assessment of intracranial vasculature. MRA is a well-validated technique that offers great advantage over traditional angiography. Advances in high-resolution MR imaging of MCA stenosis have the potential to yield excellent visualization of plaque. Future developments in high-resolution MR imaging to depict intracranial atherosclerosis are explored in this review; these advances will guide endovascular therapy and the comparison of novel interventions.

Identification and characterization of multiple splice forms of the human interleukin-23 receptor alpha chain in mitogen-activated leukocytes.

The signalling of interleukin-23 (IL-23) and its receptor (IL-23R) is a key element in the differentiation of T cells to the Th17 phenotype. Here, we present the identification and characterization of human IL23R splice variants resulting from alternative splicing of the IL23R mRNA, from activated human leukocytes, following the analysis of IL23R cDNA. Twenty-four different IL23R transcripts were observed in this study, which may potentially lead to an alteration in the protein coding region of IL-23R alpha. Consequently, by analysing amino acid sequences deduced from alternatively spliced mRNA sequences, four different putative premature early termination forms of IL-23R alpha: (1) a very short 'IL-23R alpha', (2) an IL-23R alpha containing only the extracellular region, (3) a IL-23R alpha with truncated intracellular domain and (4) in-frame exon-skipping causing changes to the extracellular region of the IL-23R alpha were revealed. These changes may affect the function of IL-23R by altering the ligand-binding interaction, producing a soluble form of the receptor to act as a decoy receptor and/or modify the IL-23/IL-23R signalling, respectively. Taken together, identification of potentially functional splice variants of IL23R underscores the biological diversity of the IL23R gene and will aid in the understanding of the gene's function in normal and pathological conditions.

A novel insertion variant of the human IL-23 receptor-alpha chain transcript.

Alternative splicing of mRNA is an important mechanism for organisms to enhance protein diversity from a limited number of genes. In this report, we described a novel exon insertion in the interleukin 23 (IL-23) receptor between exons 9 and 10, denoted as exon 9a. This 162 base-pair insertion was the only insertion variant discovered in more than 20 IL23R deletion variants found in the mRNA of mitogen-stimulated peripheral blood mononuclear cells (PBMC). Sequence analysis revealed that a pair of GT/AG splice donor-acceptor site and several putative cis-acting sequences were present; the insertion was identified throughout the genome and found to contain homology to the L1 retrotransposon protein. This report describes an insertion in the IL-23 receptor and due to consequent early termination within the intracellular region, causing a possible non-responsive receptor isoform.

Differential regulation of innate immune response genes in gingival epithelial cells stimulated with Aggregatibacter actinomycetemcomitans.

BACKGROUND AND OBJECTIVE: The gingival epithelium provides the first line of defense against colonization by periodontal pathogens, both as a physical barrier and by the production of inducible innate immune mediators such as beta-defensins and pro-inflammatory cytokines. The gram-negative bacterium Aggregatibacter actinomycetemcomitans is implicated in the pathogenesis of localized aggressive periodontitis, although the bacterium is found widely in the healthy population. We hypothesized that gingival epithelial cell-derived innate immune mediators triggered in response to A. actinomycetemcomitans infection may play an important role in increased susceptibility to infection. MATERIAL AND METHODS: Primary cultures of human gingival epithelial cells were cultured in the presence of A. actinomycetemcomitans. Total mRNA was examined for the presence of innate immune markers using RT-PCR. RESULTS: We show here that the mRNA levels of human beta-defensin 2 and interleukin-8 are elevated by live cultures of a clinical isolate of A. actinomycetemcomitans in cultured gingival epithelial cells from healthy individuals, but not by A. actinomycetemcomitans lipopolysaccharide. Cells from a patient with localized aggressive periodontitis, however, did not respond to this bacterial stimulation. In contrast, the pro-inflammatory cytokine interleukin-19 was induced in cells from both localized aggressive periodontitis and healthy subjects. Examination of Toll-like receptors and associated adapter molecules indicated lower levels of Toll-like receptor 2 mRNA in the localized aggressive periodontitis patient-derived cells compared with cells from healthy subjects. CONCLUSION: These results suggest that a differential expression of innate immune response genes to A. actinomycetemcomitans in the gingival epithelium could be an underlying factor of susceptibility to localized aggressive periodontitis.

Human interferon lambda-1 (IFN-lambda1/IL-29) modulates the Th1/Th2 response.

Interferon lambda-1 (IFN-lambda1/IL-29) is a member of the Type-III interferon family, which contains three ligands: IFN-lambda1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-lambda-R1/IL-28Ralpha) and CRF2-4 (IL10-R-beta) chains. Like their close relatives, the Type-I interferons, IFN-lambda1, 2 and 3, promote the phosphorylation of STAT1 and STAT2, induce the ISRE3 complex, elevate OAS and MxA expression and exhibit antiviral activity in vitro. Their use of the IL10-R-beta chain and their ability to phosphorylate STAT3, STAT4 and STAT5 suggested that they may also exhibit immunomodulatory activity; their antiviral action led us to hypothesize that this activity might be directed toward the Th1/Th2 system. Here, we have demonstrated that IFN-lambda1 altered the activity of Th cells in three separate experimental systems: (i) mitogen stimulation, (ii) mixed-lymphocyte reaction (MLR) and (iii) stimulation of naive T cells by monocyte-derived dendritic cells (mDC). In Con-A stimulation assays, the inclusion of IFN-lambda1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-gamma. IL-13 secretion was 100-fold more sensitive to IFN-lambda1 than was IFN-gamma secretion. These observations were also made in the allogeneic two-way MLR. IFN-lambda1 was able to alter cytokine-mediated Th biasing and when naive T cells were exposed to allogeneic mDC that had been matured in the presence of IFN-lambda1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-gamma was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-lambda1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.

Selective use of older adults in right lobe living donor liver transplantation.

Many centers are reluctant to use older donors (>44 years) for adult right-lobe living donor liver transplantation (RLDLT) due to concerns about possible increased morbidity in donors and poorer outcomes in recipients. Since 2000, 130 adult RLDLTs have been performed at our institution. Recipients were divided into those who received a right lobe graft from a donor 44 (n = 41, 32%; mean age 52). The two donor and recipient populations had similar demographic and operative profiles. With a median follow-up of 29 months, the severity and number of complications in older donors were similar to those in younger donors. No living donor died. Older donor allografts had initial allograft dysfunction compared to younger donors. Complication rates were similar among recipients in both groups but there was a higher bile duct stricture rate with older donor grafts (27% vs. 12%; p = 0.04). One-year recipient graft survival was 86% for older donors and 85% for younger donors (p = 0.95). Early experience with the use of selected older adults (>44 years) for RLDLT is encouraging, but may be associated with a higher rate of biliary complications in the recipient.

Interferon lambda-1 (IFN-lambda1/IL-29) induces ELR(-) CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-gamma-independent manner.

Interferon lambda-1 (IFN-lambda1), the prototype Type-III interferon, has antiviral functions similar to those of the Type-I interferons, IFN-alpha and IFN-beta. However, IFN-lambda1 is capable of signaling through almost all STAT molecules and so it is possible that it may have novel immunoregulatory functions in addition to antiviral ones. From a range of chemokines tested, IFN-lambda1 elevated mRNA levels of only 'Monokine induced by IFN-gamma' (MIG/CXCL9), 'IFN-gamma inducible protein-10' (IP-10/CXCL10) and 'IFN-gamma inducible T-cell alpha chemoattractant' (I-TAC/CXCL11) from human peripheral blood mononuclear cells. As their names suggest, these chemokines are also induced by IFN-gamma, the only member of the Type-II interferon family. This action of IFN-lambda1 did not depend on intermediate induction of IFN-gamma and is therefore, likely to be independent of IFN-gamma. Further, our results suggest that donors responded to IFN-lambda1 stimulation either 'early' or 'late'. Overall the action of IFN-lambda1 was similar to that previously reported for IFN-gamma and may invite more detailed investigation of the role of IFN-lambda1 at the innate/adaptive interface.

Modulation of the human cytokine response by interferon lambda-1 (IFN-lambda1/IL-29).

The interferon lambda family (IFN-lambda1/2/3) is a newly described group of cytokines that are related to both the type-1 interferons and IL-10 family members. These novel cytokines are induced during viral infection and, like type-1 interferons, display significant anti-viral activity. In order to understand their function in more depth, we have examined the ability of IFN-lambda1/IL-29 to regulate cytokine production by human immune cells. Whole peripheral blood mononuclear cells (PBMC) exposed to IFN-lambda1 specifically upregulated IL-6, -8 and -10 but there were no visible effects on TNF or IL-1. This response was produced in a dose-dependant fashion and was inhibited by IL-10. Examination of purified cell populations isolated from PBMC demonstrated that monocytes, rather than lymphocytes, were the major IFN-lambda1-responsive cellular subset, producing IL-6, -8 and -10 in response to IFN-lambda1. Monocyte responses induced by low-level LPS stimulation were also synergistically enhanced by the presence of IFN-lambda1. Human macrophages were also shown to react to IFN-lambda1 similarly to monocytes, by producing the cytokines IL-6, -8 and -10. In conclusion, we have shown that IFN-lambda1, a cytokine produced in response to viral infection, activates both monocytes and macrophages producing a restricted panel of cytokines and may therefore be important in activating innate immune responses at the site of viral infection.

Blood splash from different diathermy instruments during tonsillectomy.

OBJECTIVE: To compare the potential risk of blood contamination of the surgeon's conjunctiva during tonsillectomy using disposable bipolar diathermy and reusable monopolar diathermy. DESIGN: A prospective, single-blind, randomized, controlled trial. METHODS: Elective tonsillectomy was performed using either disposable bipolar diathermy or reusable monopolar diathermy. The operating surgeon wore a ViewsafeTM protective eyeshield which was later examined under an operating microscope by a blinded observer and the number of blood spots counted. RESULTS: One hundred and sixty-eight patients were enrolled. The relative risk of conjunctival contamination of the surgeon using disposable bipolar diathermy was 2.8 times that with reusable monopolar diathermy (chi-squared test, p < 0.0005). A previous history of peritonsillar abscess and additional adenoidectomy were associated with increased blood splatter. CONCLUSION: The use of disposable bipolar diathermy for haemostasis during tonsillectomy poses a greater risk of conjunctival contamination for the surgeon than using reusable monopolar diathermy.

A non-conservative, coding single-nucleotide polymorphism in the N-terminal region of lactoferrin is associated with aggressive periodontitis in an African-American, but not a Caucasian population.

Lactoferrin is an antimicrobial protein which plays an important role in regulating bacteria that are associated with aggressive periodontitis. Lactoferrin kills directly (via its strongly cationic N-terminal region) and indirectly, through sequestering the iron that bacteria require for growth. As aggressive periodontitis has a strong heritable component, we hypothesized that genetic variation within the lactoferrin gene may play a role in susceptibility to this condition. We have identified and examined a novel, functional, single-point A/G nucleotide mutation causing a threonine/alanine substitution at position 11 (T11A) of the secreted lactoferrin protein. In a pilot case-controlled study of aggressive periodontitis, analysis of 46 African-American patients and 78 controls showed that patients were twice as likely to express the G nucleotide (alanine) allele over controls (60.3 vs 30.4%; P=0.0007, odds ratio=2.564, 95% CI=1.475-4.459). A Caucasian population of 77 patients and 131 controls showed no such association (P=0.5201, odds ratio=0.862, 95% CI=0.548-1.356). The data presented provide a new insight into the genetic susceptibility to aggressive periodontitis.

Antimicrobial susceptibility patterns in Pseudomonas aeruginosa: data from a multicenter Intensive Care Unit Surveillance Study (ISS) in the United States.

The objectives of this study were to analyze susceptibility rates and patterns in Pseudomonas aeruginosa isolates from patients in intensive care units (ICU). A total of 2209 isolates in 1995/1996 and 2672 in 2001/2002 were tested at United States sites participating in the ICU Surveillance Study. In both periods, of the agents tested, amikacin was the most active and ciprofloxacin, the least. Resistance to common antipseudomonal agents tested increased from 1995/1996 to 2001/2002; the rise was least for amikacin (2%) and greatest for ciprofloxacin (16%). The proportion of isolates susceptible to all six antipseudomonal agents tested since 1996 decreased from 60.4% to 48.9% in 2001/2002. Examination of MIC distributions for the two periods showed that for some drugs, e.g. imipenem and ceftazidime, the populations of susceptible and resistant isolates remained distinct, although the resistant population increased. For other drugs, e.g. amikacin and piperacillin-tazobactam, the MIC distribution shifted upward over time. The categorical agreement between agents of the same or like classes for isolates tested in 2001/2002 was highest for ciprofloxacin and levofloxacin (93.2%, with 1.2% major errors) and lowest for the aminoglycosides (81.3%, with 10.2% major errors). We can conclude that resistance to antipseudomonal agents among ICU isolates of P. aeruginosa, especially fluoroquinolones, is increasing. The resistance rate for some antipseudomonal agents may not accurately reflect shifts in the MIC distribution curve.

Complex nature of the human antisperm antibody response in SCID mice.

Human peripheral blood mononuclear (PBMs) cells were introduced into the peritoneal cavity of severely-combined immunodeficient (SCID) mice in concentrations of 2.5-4.0 x 10(7) cells per mouse. Whole mononuclear cell suspensions were used either unstimulated or following primary in vitro culture with human spermatozoa. In some experiments, immunodepletion of CD8(+) cells was carried out prior to grafting. Lymphocytes were obtained from nonsensitized (to antigen) human subjects or from individuals who were primed in vivo (vasectomized individuals in case of sperm antigens). An enzyme-linked immunosorbent assay was employed to assess total human immunoglobulin (G or M) levels as well as the specificity of the antibodies generated. We have been successful by generating primary and secondary immune responses with 'naïve' human lymphocytes, challenged with chlamydia or ovalbumin but without adjuvant or CD8(+) immunodepletion; however, we were unable to induce specific antibodies to spermatozoa under this regime in SCID male mice. We then employed female SCID mice, treated with sperm antigen extracts (glycosylated or deglycosylated) encapsulated in liposomes and human lymphocytes obtained from 'naïve' or pre-sensitized in vivo subjects. It was found that the most pronounced humoral response to sperm antigens was obtained with deglycosylated antigens and PBMs from vasectomized (in vivo pre-primed to spermatozoa) individuals. A presented SCID mice model can be helpful at understanding of antisperm antibody development and the molecular nature of generated antibodies to modified sperm antigenic entities.

Stationary-phase acid resistance and injury of recent bovine Escherichia coli O157 and non-O157 biotype I Escherichia coli isolatest.

Stationary-phase acid resistance and the induction of acid resistance were assessed for recent bovine carcass isolates of Escherichia coli, including 39 serotype O157 strains and 20 non-O157 strains. When grown to stationary phase in the absence of glucose and without prior acid exposure, there was a range of responses to a pH challenge of 6 h at pH 2.5. However, populations of 53 of the 59 E. coli isolates examined were reduced by less than 2.00 log CFU/ml, and populations of 24 of these isolates were reduced by less than 1.00 log CFU/ml. In contrast, there was little variation in population reductions when the E. coli were grown with glucose and preadapted to acidic conditions. With few exceptions, acid adaptation improved survival to the acid challenge, with 57 of the 59 isolates exhibiting a log reduction of less than 0.50. Differences in acid resistance or the ability to adapt to acidic conditions between E. coli O157:H7 and non-O157 commensal E. coli were not observed. However, we did find that the E. coli O157 were disposed to greater acid injury after the low pH challenge than the non-O157 E. coli, both for cells that were and were not adapted to acidic conditions before the challenge. The enhancement of low pH survival after acid adaptation that was seen among these recent natural isolates of E. coli O157 further supports the idea that the previous environment of this pathogen should be a consideration when designing microbial safety strategies for foods preserved by low pH and acid.

Closing the audit loop--prevention of perioperative hypothermia: audit and reaudit of perioperative hypothermia.

BACKGROUND AND OBJECTIVE: Perioperative hypothermia is generally regarded as undesirable, but its incidence rate in the elective procedures in our hospital and the effect of the preventative measures taken against it were unknown. An initial audit indicated that postoperative hypothermia occurred. Therefore, changes in practice were implemented to address the problem. A further audit was then undertaken to assess the impact of these measures. METHODS: The first audit recorded data from 177 patients undergoing major elective surgical procedures. Variables recorded were: ASA classification, duration of operation, use and description of preventative measures for hypothermia, blood loss, intravenous fluids, and core and peripheral temperatures on arrival and discharge from the recovery room. The subsequent audit included 158 patients undergoing major general, orthopaedic or vascular surgical procedures. Patients had core temperatures measured preoperatively, immediately upon arrival in the recovery room, and just before discharge back to the ward. Core temperatures in both audits were measured using an infrared temperature probe. RESULTS: The mean body temperature on arrival in the recovery room of patients in the initial audit was 35.5 degrees C (range 32.2-37.2, SD +/- 0.74), and in the subsequent audit 36.6 degrees C (33.6-38.2, +/- 0.72). These differences reached significance (P < 0.0001). This was despite an average duration of surgery of 133.5 (25-330) min in the initial study compared with 154.7 (90-480) min subsequently. CONCLUSIONS: We found that with simple but consistently implemented changes in practice, postoperative hypothermia in elective patients could largely be eradicated.

A novel treatment for patients with hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by dermal, mucosal, and visceral telangiectases as well as pulmonary and cerebral arteriovenous malformations. Recurrent epistaxis occurs in the majority of patients, and by the very nature of the thin walled vessels involved it is often refractory to conventional forms of treatment. We present the case of an 82-year-old lady with intractable epistaxis secondary to HHT, that was successfully controlled by the application of fibrin glue.