Immediate reporting of chest X-rays referred from general practice by reporting radiographers: a single centre feasibility study.

AIM: To investigate the feasibility of radiographer-led immediate reporting of chest radiographs (CXRs) referred from general practice. MATERIALS AND METHODS: This 4-month feasibility study (November 2016 to March 2017) was carried out in a single radiology department at an acute general hospital. Comparison was made between CXRs that received an immediate and routine report to determine the number of lung cancers diagnosed, time to diagnosis of lung cancer, time to computed tomography (CT), and number of urgent referrals to respiratory medicine. RESULTS: Forty of 186 sessions (22%) were covered by radiographer immediate reporting. Of the 1,687 CXRs referred from general practice, 558 (33.1%) received an immediate report (radiographer or radiologist). Twenty-two (of 36) CT examinations performed were following an abnormal CXR with an immediate report (mean 0.8 scans/week). Time from CXR to CT was shorter in the immediate report group (n=22 mean 0.9 days SD=2.3) compared to routine reporting (n=14; mean 6.5 SD=3.2; F=27.883, p<0.0001). Time to multidisciplinary team (MDT) discussion was shorter in the immediate reporting group (mean 4.1 SD=2.9) compared to routine reporting (mean 10.6; SD=4.5; F=11.59, p<0.0001). No apparent difference was found for time to discussion at treatment MDT. CONCLUSION: It is feasible to introduce a radiographer-led immediate CXR reporting service. Patients can be taken off the lung cancer pathway sooner with the introduction of radiographer immediate reporting of CXRs and this may improve outcomes for patients. A definitive study assessing outcomes is required to determine whether this will have an impact mortality and morbidity for patients.

Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) is associated with improved survival compared with HPV-negative disease. However, a minority of HPV-positive patients have poor prognosis. Currently, there is no generally accepted strategy for identifying these patients. METHODS: We retrospectively analysed 270 consecutively treated OPSCC patients from three centres for effects of clinical, pathological, immunological, and molecular features on disease mortality. We used Cox regression to examine associations between factors and OPSCC death, and developed a prognostic model for 3-year mortality using logistic regression analysis. RESULTS: Patients with HPV-positive tumours showed improved survival (hazard ratio (HR), 0.33 (0.21-0.53)). High levels of tumour-infiltrating lymphocytes (TILs) stratified HPV-positive patients into high-risk and low-risk groups (3-year survival; HPV-positive/TIL(high)=96%, HPV-positive/TIL(low)=59%). Survival of HPV-positive/TIL(low) patients did not differ from HPV-negative patients (HR, 1.01; P=0.98). We developed a prognostic model for HPV-positive tumours using a 'training' cohort from one centre; the combination of TIL levels, heavy smoking, and T-stage were significant (AUROC=0·87). This model was validated on patients from the other centres (detection rate 67%; false-positive rate 5.6%; AUROC=0·82). INTERPRETATION: Our data suggest that an immune response, reflected by TIL levels in the primary tumour, has an important role in the improved survival seen in most HPV-positive patients, and is relevant for the clinical evaluation of HPV-positive OPSCC.

A pilot study to assess radiographer preliminary clinical evaluation (PCE) introduced for emergency department adult appendicular X-ray examinations: Comparison of trained and untrained radiographers.

INTRODUCTION: Radiographers are transitioning from using "Red Dot" annotations to flag abnormal emergency X-ray images, to providing written preliminary clinical evaluation (PCE) diagnostic comments. This study explored the impact of local training on radiographers' PCE participation and accuracy performance during a trial period. METHODS: Ten radiographers provided PCE comments for adult appendicular trauma X-ray examinations performed in the Emergency Department of an English public hospital over a 19 week trial period. Five senior radiographers who had received local PCE training and five more recently qualified radiographers, without this local training, participated in the trial. PCE participation rates were recorded and the PCE comments were scored for accuracy compared to the formal radiology report. RESULTS: There were 796 eligible examinations, of which 528 (66%) had PCE comments. PCE participation was significantly higher (p < 0.001) for the radiographer group who received the training (80%, 253/316) compared to the untrained group (57%, 275/480). Similar levels of PCE accuracy (90% vs. 89%), sensitivity (86% vs. 82%) and specificity (91% vs. 93%) were found for the trained and untrained cohorts respectively, with no statistically significance difference between these scores. CONCLUSION: Local PCE training was associated with more frequent PCE participation but did not appear to influence PCE accuracy. The accuracy results suggest that radiographers are well equipped to provide PCE comments for adult appendicular X-ray examinations. IMPLICATIONS FOR PRACTICE: Local PCE training is likely to be important for consistent PCE scheme participation. Both experienced and recently qualified radiographers appear well equipped to provide accurate PCE for adult appendicular trauma X-ray examinations.

Concordance between a gastrointestinal consultant radiologist, a consultant radiologist and qualified reporting radiographers interpreting abdominal radiographs.

INTRODUCTION: Radiographers can accurately report musculoskeletal and chest radiographs, but there is paucity of research comparing the performance of reporting radiographers (RRs) with consultant radiologists when interpreting and reporting abdominal radiographs. This study assessed interobserver agreement in the clinical setting between reporting radiographers and a consultant radiologist compared to an expert gastrointestinal radiologist in a District General Hospital. Major discordant reports affecting patient management were also examined. METHODS: 126 abdominal radiographs reported by 3 RRs in clinical practice were randomly selected and reported by a consultant radiologist and index gastrointestinal radiologist. The reports of the RRs and consultant radiologist were compared against the reports made by the index radiologist for agreement by a colorectal consultant surgeon. All 126 reports were scored as being in either complete agreement, minor disagreement or major disagreement which would have resulted in a change to patient management. RESULTS: There was no significant difference in overall agreement between the consultant radiologist (CR) and RRs when compared to the index radiologist (CR: n = 90/126, 71.4% and RRs: n = 94/126, 74.6%. p = 0.57). Major disagreements were found, but there was no significant difference between both groups (CR: n = 23/126, 18.3% and RRs: n = 17/126, 13.5%. p = 0.30). CONCLUSION: RRs can report abdominal radiographs to a comparable level of agreement as a consultant radiologist in the clinical setting. There was no significant difference in reports deemed to affect patient management. IMPLICATIONS FOR PRACTICE: This study addresses the gap in assessing the performance of RRs reporting abdominal radiographs. This small scale study indicates that radiographers could provide additional support in the reporting of abdominal radiographs. This would help to reduce radiologist workload and enhance the role of the reporting radiographer. CLASSIFICATION: Agreement between reporting radiographers and radiologists interpreting and reporting abdominal radiographs.

Accuracy of radiographer preliminary clinical evaluation of skeletal trauma radiographs, in clinical practice at a district general hospital.

INTRODUCTION: Error in interpretation of trauma radiographs by referrers is a problem which has detrimental effects on the patient and causes unnecessary repeat attendances. Radiographers can reduce errors by offering their opinion at the time of imaging. The Society and College of Radiographers have a longstanding recommendation that Red Dot (RD) schemes should be replaced by Preliminary Clinical Evaluation (PCE). The purpose of the study was to evaluate radiographer interpretation of skeletal trauma radiographs in clinical practice, determine if there was any difference in ability to interpret appendicular and axial studies, and evaluate appropriateness of PCE implementation. METHODS: A convenience sample of 23 self-selecting radiographers provided RD and PCE on 762 examinations. Each case was compared against the verified report and assigned a true negative/positive or false negative/positive value. Accuracy, sensitivity and specificity were calculated and performance measures between RD versus PCE, and appendicular versus axial were compared using Two-sample Z-Tests. Error analysis was performed and inter-observer consistency determined. RESULTS: Overall RD and PCE accuracy, sensitivity and specificity for the study were 90%, 72% and 97% (RD), and 92%, 80% and 97% (PCE) respectively. Significant difference was demonstrated for sensitivity with PCE more sensitive than RD (p-value 0.03) and appendicular more sensitive than axial (RD p-value <0.02, PCE p-value <0.0001). Most errors were false negatives. Inter-observer consistency was evaluated by review of 128 cases and no difference between reviewers was established. CONCLUSION: Radiographers without specific training were able to provide RD and PCE to a high standard. Radiographers interpreted positive findings more accurately using PCE than RD, and positive findings on appendicular cases were interpreted more accurately than those on axial cases. IMPLICATIONS FOR PRACTICE: This study supports local PCE implementation, contributes to the wider evidence base to justify transition towards PCE and identifies the necessity for local axial image interpretation training.

Agreement in the reporting of General Practitioner requested musculoskeletal radiographs: Reporting radiographers and consultant radiologists compared with an index radiologist.

INTRODUCTION: This study assessed the inter-observer agreement of reporting radiographers and consultant radiologists compared with an index radiologist when reporting General Practitioner (GP) requested musculoskeletal radiographs. The potential effect of discordant reports on patient management and outcome was also examined. METHODS: Three reporting radiographers, three consultant radiologists and an index radiologist reported on a retrospective randomised sample of 219 GP requested musculoskeletal radiographs, in conditions simulating clinical practice. A speciality doctor in radiology compared the observers' reports with the index radiologist report for agreement and assessed whether any discordance between reports was clinically important. RESULTS: Overall agreement with the index radiologist was 47.0% (95% CI, 40.5-53.6) and 51.6% (95% CI, 45.0-58.1) for the consultant radiologists and reporting radiographers, respectively. The results for the appendicular and axial skeleton were 48.6% (95% CI, 41.3-55.9) and 40.9% (95% CI, 27.7-55.6) for the radiologists, and 52.6% (95% CI, 45.2-59.8) and 47.7% (95% CI, 33.8-62.1) for the radiographers, respectively. The difference in overall observer agreement between the two professional groups with the index radiologist was not statistically significant (p = 0.34). Discordance with the index radiologist's reports was judged to be clinically important in less than 10% of the observer's reports. CONCLUSION: Reporting radiographers and consultant radiologists demonstrate similar levels of concordance with an index radiologist when reporting GP requested musculoskeletal radiographs. IMPLICATIONS FOR PRACTICE: These findings contribute to the wider evidence base that selected radiographers with appropriate postgraduate education and training are proficient to report on musculoskeletal radiographs, irrespective of referral source.

Chronic lymphocytic leukaemia cells drive the global CD4+ T cell repertoire towards a regulatory phenotype and leads to the accumulation of CD4+ forkhead box P3+ T cells.

Advanced chronic lymphocytic leukaemia (CLL) is associated with profound immunodeficiency, including changes in T regulatory cells (T(regs)). We determined the pattern of expression of forkhead box P3 (FoxP3), CD25, CD27 and CD127 and showed that the frequency of CD4+ FoxP3+ T cells was increased in CLL patients (12% versus 8% in controls). This increase was seen only in advanced disease, with selective expansion of FoxP3-expressing cells in the CD4+ CD25(low) population, whereas the number of CD4+ CD25(high) FoxP3+ cells was unchanged. CD4+ CD25(low) cells showed reduced expression of CD127 and increased CD27, and this regulatory phenotype was also seen on all CD4 T cells subsets in CLL patients, irrespective of CD25 or FoxP3 expression. Incubation of CD4+ T cells with primary CLL tumours led to a sixfold increase in the expression of FoxP3 in CD4+ CD25- T cells. Patients undergoing treatment with fludarabine demonstrated a transient increase in the percentage of CD4+ FoxP3+ T cells, but this reduced to normal levels post-treatment. This work demonstrates that patients with CLL exhibit a systemic T cell dysregulation leading to the accumulation of CD4+ FoxP3+ T cells. This appears to be driven by interaction with malignant cells, and increased understanding of the mechanisms that are involved could provide novel avenues for treatment.

Concordance between a neuroradiologist, a consultant radiologist and trained reporting radiographers interpreting MRI head examinations: An empirical study.

INTRODUCTION: This study assessed agreement between MRI reporting radiographers and a consultant radiologist compared with an index neuroradiologist when reporting MRI head (brain/internal auditory meati [IAMs]) examinations. The effect on patient management of any discordant reports was also examined. METHODS: Two trained MRI reporting radiographers (RRs), a consultant radiologist (CR) and an index neuroradiologist (INR) reported on a random sample of 210 MRI examinations. The radiographers reported during clinical practice and the radiologists in clinical practice conditions. Two independent consultant physicians (neuro-rehabilitation and neuropsychiatry) compared these reports with the index neuroradiologist report for agreement and the clinical importance of discrepant reports. RESULTS: Overall observer agreement between the RRs and CR was comparable in relation to agreement with the INR: RR; 93/210 (44.3%); and the CR; 83/210 (39.4%) for all head MRI examinations (p = 0.32). For brain examinations the difference was similar: RR; 64/180 (35.6%); and CR; 54/190 (30.0%), p = 0.26. Agreement rates for the IAMs examinations were identical, 29/30 (97.7%). For all head MRI examinations (n = 210) there was a very small observed difference of <0.5% in mean agreement between the reporting radiographers and the consultant radiologist (p = 0.92) for examinations where a major disagreement would have been likely to have led to a change in patient management. CONCLUSION: MRI reporting radiographers reported during clinical practice on MRI head examinations to a level of agreement comparable with a consultant radiologist. IMPLICATIONS FOR PRACTICE: This is an area in which radiographers could provide additional reporting roles to the reporting service to increase capacity. Wider potential benefits include cost-effectiveness and role development/retention of radiographers.

Multicenter Postmarket Analysis of the Neuroform Atlas Stent for Stent-Assisted Coil Embolization of Intracranial Aneurysms.

BACKGROUND AND PURPOSE: The Neuroform Atlas is a new microstent to assist coil embolization of intracranial aneurysms that recently gained FDA approval. We present a postmarket multicenter analysis of the Neuroform Atlas stent. MATERIALS AND METHODS: On the basis of retrospective chart review from 11 academic centers, we analyzed patients treated with the Neuroform Atlas after FDA exemption from January 2018 to June 2019. Clinical and radiologic parameters included patient demographics, aneurysm characteristics, stent parameters, complications, and outcomes at discharge and last follow-up. RESULTS: Overall, 128 aneurysms in 128 patients (median age, 62 years) were treated with 138 stents. Risk factors included smoking (59.4%), multiple aneurysms (27.3%), and family history of aneurysms (16.4%). Most patients were treated electively (93.7%), and 8 (6.3%) underwent treatment within 2 weeks of subarachnoid hemorrhage. Previous aneurysm treatment failure was present in 21% of cases. Wide-neck aneurysms (80.5%), small aneurysm size (<7 mm, 76.6%), and bifurcation aneurysm location (basilar apex, 28.9%; anterior communicating artery, 27.3%; and middle cerebral artery bifurcation, 12.5%) were common. A single stent was used in 92.2% of cases, and a single catheter for both stent placement and coiling was used in 59.4% of cases. Technical complications during stent deployment occurred in 4.7% of cases; symptomatic thromboembolic stroke, in 2.3%; and symptomatic hemorrhage, in 0.8%. Favorable Raymond grades (Raymond-Roy occlusion classification) I and II were achieved in 82.9% at discharge and 89.5% at last follow-up. mRS ≤2 was determined in 96.9% of patients at last follow-up. The immediate Raymond-Roy occlusion classification grade correlated with aneurysm location (P < .0001) and rupture status during treatment (P = .03). CONCLUSIONS: This multicenter analysis provides a real-world safety and efficacy profile for the treatment of intracranial aneurysms with the Neuroform Atlas stent.

Isolation of caprine herpesvirus 1 from a major outbreak of infectious pustular vulvovaginitis in goats.

We describe an outbreak of infectious pustular vulvovaginitis caused by Caprine herpesvirus 1 (CpHV1) in a group of approximately 200, 8 month old virgin does that were imported to Victoria from New Zealand. CpHV1 was isolated in cell cultures from vaginal swabs from three of three affected does but not from two bucks that had been with the does. The identity of the virus as a herpesvirus was confirmed by negative stain electron microscopy. Restriction endonuclease DNA fingerprint analysis showed that the DNA fingerprints were similar, but not identical, to previously described CpHV1 isolates made in New Zealand, New South Wales, and in other parts of the world. Acute and convalescent phase sera from selected does supported the diagnosis of CpHV1 infection. It is most likely that the disease was initiated by reactivation of latent virus in at least one of four bucks that served the does, since each was positive for CpHV neutralising antibody when first tested. This is the first report of CpHV infectious pustular vulvovaginitis in goats in Victoria and to our knowledge appears to be one of the largest outbreaks recorded anywhere.

Radiographer reporting of neurological magnetic resonance imaging examinations of the head and cervical spine: Findings of an accredited postgraduate programme.

INTRODUCTION: To analyse the objective structured examination (OSE) results of the first cohorts of radiographers (n = 13) who successfully completed an accredited postgraduate programme in clinical reporting of neurological magnetic resonance imaging (MRI) examinations of the head and cervical spine. METHODS: Forty MRI examinations were used in the OSE which included a range of abnormal cases (prevalence of abnormal examinations approximated 50%) and included: haemorrhage, infarction, demyelination disease, abscess, mass lesions (metastatic deposits, meningioma, glioma, astrocytoma); and disc disease, cord compression, stenosis, ligament rupture, syringomyelia appearances on patients referred from a range of referral sources. Normal variants and incidental findings were also included. True/false positive and negative fractions were used to mark the responses which were also scored for agreement with the previously agreed expected answers based on agreement between three consultant radiologists' reports. RESULTS: The mean sensitivity, specificity and agreement rates for all head and cervical spine investigations (n = 520) combined were 98.86%, 98.08% and 88.37%, respectively. The highest scoring cases were cases which included astrocytoma, disc protrusion with cord compression and glioma. The most common errors were related to syringomyelia, ligament rupture and vertebral fracture. CONCLUSIONS: These OSE results suggest that in an academic setting, and following an accredited postgraduate education programme, this group of radiographers has the ability to correctly identify normal MRI examinations of the head/cervical spine and are able to provide a report on the abnormal appearances to a high standard. Further work is required to confirm the clinical application of these findings.

Agreement between expert thoracic radiologists and the chest radiograph reports provided by consultant radiologists and reporting radiographers in clinical practice: Review of a single clinical site.

INTRODUCTION: To compare the clinical chest radiograph (CXR) reports provided by consultant radiologists and reporting radiographers with expert thoracic radiologists. METHODS: Adult CXRs (n = 193) from a single site were included; 83% randomly selected from CXRs performed over one year, and 17% selected from the discrepancy meeting. Chest radiographs were independently interpreted by two expert thoracic radiologists (CTR1/2).Clinical history, previous and follow-up imaging was available, but not the original clinical report. Two arbiters compared expert and clinical reports independently. Kappa (Ƙ), Chi Square (χ2) and McNemar tests were performed to determine inter-observer agreement. RESULTS: CTR1 interpreted 187 (97%) and CTR2 186 (96%) CXRs, with 180 CXRs interpreted by both experts. Radiologists and radiographers provided 93 and 87 of the original clinical reports respectively. Consensus between both expert thoracic radiologists and the radiographer clinical report was 70 (CTR1; Ƙ = 0.59) and 70 (CTR2; Ƙ = 0.62), and comparable to agreement between expert thoracic radiologists and the radiologist clinical report (CTR1 = 76, Ƙ = 0.60; CTR2 = 75, Ƙ = 0.62). Expert thoracic radiologists agreed in 131 cases (Ƙ = 0.48). There was no difference in agreement between either expert thoracic radiologist, when the clinical report was provided by radiographers or radiologists (CTR1 χ = 0.056, p = 0.813; CTR2 χ = 0.014, p = 0.906), or when stratified by inter-expert agreement; radiographer McNemar p = 0.629 and radiologist p = 0.701. CONCLUSION: Even when weighted with chest radiographs reviewed at discrepancy meetings, content of CXR reports from trained radiographers were indistinguishable from content of reports issued by radiologists and expert thoracic radiologists.

Persistence of fetal cells in the mother: friend or foe?

There is increasing evidence that both circulating cells and free fetal DNA persist in the maternal circulation after delivery of the fetus. In some cases, this has been described many years after the end of the pregnancy. This article reviews the evidence for these cells being present, the potential methodologies used to identify such cells and the potential effects on maternal immunomodulation. Data relating to the potential beneficial and potentially harmful effects are discussed.

Novel SOX9 expression during human pancreas development correlates to abnormalities in Campomelic dysplasia.

Haploinsufficiency of SOX9, which encodes a homeodomain transcription factor, results in Campomelic dysplasia. Classical features of this disorder (e.g. skeletal dysplasia and 46,XY sex reversal) are in concordance with SOX9 expression profiles during human embryonic development. We report the robust expression of SOX9 throughout the pancreas during human embryogenesis, at levels of detection equivalent to the developing skeleton and testis. In the early foetal period, SOX9 expression declines and, in particular, is not apparent within the pancreatic islets. In keeping with this profile, examination of three cases with Campomelic dysplasia revealed abnormal pancreatic morphology. Epithelial cells were less densely packed within the mesenchymal stroma and islets less clearly formed with variable expression of hormone and beta cell markers. Taken together, these data indicate a novel potential role for SOX9 in pancreas development during human embryogenesis and early foetal life.

Characterization of a schistosome T cell-stimulating antigen (Sm10) associated with protective immunity in humans.

Parasite antigens that are strong T cell immunogens represent potential candidates for vaccines against pathogens susceptible to T cell-mediated immunity. We have previously shown that chromatographic fractions of schistosomula extracts contain components that are major T cell immunogen(s) in natural schistosome infections in humans and might contribute to the induction of human protective immunity against this parasite. In the present study, we report on the molecular cloning and on the biochemical characterization of the active components of these fractions. The screening of a schistosomula cDNA expression library with antibodies raised against the fractions allowed the cloning of a cDNA that hybridized to a 0.56-kb mRNA of schistosomula and adult worms. This cDNA contains an open reading frame of 267 base pairs (bp) which encodes a 10-kDa polypeptide. The analysis of the cDNA sequence revealed 70% homology with the sequences of previously reported proteins of unknown function. The native molecules in the active fractions were analyzed by mass spectrometry after additional purification by reverse phase high-performance liquid chromatography (HPLC). This procedure revealed two components in the fractions of molecular mass 10383 +/- 2 Da and 10401 +/- 9 Da. Both polypeptides stimulated immune T cells and yielded tryptic peptides whose sequences matched the sequence of the cloned molecule. These two polypeptides probably correspond to different post-translationally modified forms of the polypeptide encoded by the cloned cDNA.

Beta cell differentiation during early human pancreas development.

Understanding gene expression profiles during early human pancreas development is limited by comparison to studies in rodents. In this study, from the inception of pancreatic formation, embryonic pancreatic epithelial cells, approximately half of which were proliferative, expressed nuclear PDX1 and cytoplasmic CK19. Later, in the fetal pancreas, insulin was the most abundant hormone detected during the first trimester in largely non-proliferative cells. At sequential stages of early fetal development, as the number of insulin-positive cell clusters increased, the detection of CK19 in these cells diminished. PDX1 remained expressed in fetal beta cells. Vascular structures were present within the loose stroma surrounding pancreatic epithelial cells during embryogenesis. At 10 weeks post-conception (w.p.c.), all clusters containing more than ten insulin-positive cells had developed an intimate relationship with these vessels, compared with the remainder of the developing pancreas. At 12-13 w.p.c., human fetal islets, penetrated by vasculature, contained cells independently immunoreactive for insulin, glucagon, somatostatin and pancreatic polypeptide (PP), coincident with the expression of maturity markers prohormone convertase 1/3 (PC1/3), islet amyloid polypeptide, Chromogranin A and, more weakly, GLUT2. These data support the function of fetal beta cells as true endocrine cells by the end of the first trimester of human pregnancy.

The role of T cells in vaccine immunity in the murine model of schistosomiasis mansoni.

Naive CBA/Ca mice and mice vaccinated with gamma-irradiated cercariae of Schistosoma mansoni were challenged percutaneously with normal cercariae and depleted of L3T4+ T helper cells through the administration of a specific monoclonal antibody. Three regimes were utilized to target known phases of parasite migration. The in vivo depletion of L3T4+ cells resulted in a significant reduction in immunity (up to 65%) in vaccinated/challenged mice, provided the monoclonal antibody was targeted towards skin-resident schistosomula. When antibody was targeted towards lung phase challenge larvae, however, there was a significant reduction in worm recovery, but no correspondingly significant reduction in vaccine immunity. In contrast, the administration of monoclonal to naive mice, via all three treatment regimes, had no effect on the primary schistosome worm burden. Histopathological studies complemented these worm recovery data. Skin tissue biopsied from vaccinated/challenged mice treated with monoclonal to L3T4+ T cells rarely showed the inflammatory foci which normally characterize untreated vaccinated/challenged mice. This was true when antibody was given either before challenge, or just after challenge, and correlated with the recorded depression in vaccine immunity. Lung tissue collected from monoclonal-treated vaccinated/challenged mice (for all three treatment regimes) exhibited no changes in morphology compared to that from untreated vaccinated/challenged mice. This was not altogether surprising since in the NIMR vaccine mouse model, the lungs represent a poor site for challenge attrition and appear normal in morphology with the exception of a few, small inflammatory reactions. When the monoclonal was given to naive/infected mice, there was no change in the morphology of the pulmonary tissue, as compared to corresponding untreated cohorts. Immunohistochemical studies revealed that Thy-1+ cells dominated the subdermal inflammatory foci of vaccinated/challenged mice. Of the T cells identified, the T helper subset was the most common, with T suppressor cells being only weakly represented, and in some cases not at all. The proportion of macrophages (Mac-1+) varied between reactions.

In vitro activity of GAR-936 against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae.

We report the activity of the new glycylcycline antimicrobial agent GAR-936 against 37 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes), 26 clinical isolates of methicillin-resistant S. aureus and 30 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci, methicillin-resistant S. aureus, and penicillin-resistant S. pneumoniae were inhibited by < or = 1, < or = 2, or < or = 0.25 microg/ml of GAR-936, respectively. Time kill experiments using vancomycin-resistant enterococci did not demonstrate synergy or antagonism between 2 microg/ml of GAR-936 and 0.25 microg/ml of quinupristin/dalfopristin.

In vitro activity of linezolid against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae.

We report the activity of the new oxazolidinone antimicrobial agent linezolid against 37 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes), 26 clinical isolates of methicillin-resistant S. aureus and 20 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci were inhibited by < or = 4 ug/ml of linezolid. All isolates of methicillin-resistant S. aureus were inhibited by < or = 8 ug/ml of linezolid. All isolates of penicillin-resistant S. pneumoniae were inhibited by < or = 2 ug/ml of linezolid. Linezolid inhibits strains of multidrug resistant Gram-positive cocci in vitro at concentrations < or = 8 ug/ml.

In vitro activity of LY333328 against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and penicillin-resistant Streptococcus pneumoniae.

We report the activity of LY333328 against 35 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes, as determined by PCR), 33 clinical isolates of methicillin-resistant S. aureus, and 29 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci were inhibited by 2 micrograms/mL LY333328, and 8 micrograms/mL LY333328 was bactericidal against all isolates tested. All isolates of methicillin-resistant S. aureus were inhibited by 1 microgram/mL LY333328, and 4 micrograms/mL LY333328 was bactericidal against all methicillin-resistant S. aureus isolates tested. All isolates of penicillin-resistant S. pneumoniae were inhibited by < 0.125 microgram/mL LY333328, and 0.25 microgram/mL LY333328 was bactericidal against all S. pneumoniae isolates tested. LY333328 is a promising new glycopeptide antimicrobial agent.