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Objectives Successful lung cancer screening delivery requires sensitive, timely reporting of low-dose computed tomography (LDCT) scans, placing a demand on radiology resources. Trained non-radiologist readers and computer-assisted detection (CADe) software may offer strategies to optimise the use of radiology resources without loss of sensitivity. This report examines the accuracy of trained reporting radiographers using CADe support to report LDCT scans performed as part of the Lung Screen Uptake Trial (LSUT). Methods In this observational cohort study, two radiographers independently read all LDCT performed within LSUT and reported on the presence of clinically significant nodules and common incidental findings (IFs), including recommendations for management. Reports were compared against a ‘reference standard’ (RS) derived from nodules identified by study radiologists without CADe, plus consensus radiologist review of any additional nodules identified by the radiographers. Results A total of 716 scans were included, 158 of which had one or more clinically significant pulmonary nodules as per our RS. Radiographer sensitivity against the RS was 68–73.7%, with specificity of 92.1–92.7%. Sensitivity for detection of proven cancers diagnosed from the baseline scan was 83.3–100%. The spectrum of IFs exceeded what could reasonably be covered in radiographer training. Conclusion Our findings highlight the complexity of LDCT reporting requirements, including the limitations of CADe and the breadth of IFs. We are unable to recommend CADe-supported radiographers as a sole reader of LDCT scans, but propose potential avenues for further research including initial triage of abnormal LDCT or reporting of follow-up surveillance scans. Key Points • Successful roll-out of mass screening programmes for lung cancer depends on timely, accurate CT scan reporting, placing a demand on existing radiology resources. • This observational cohort study examines the accuracy of trained radiographers using computer-assisted detection (CADe) software to report lung cancer screening CT scans, as a potential means of supporting reporting workflows in LCS programmes. • CADe-supported radiographers were less sensitive than radiologists at identifying clinically significant pulmonary nodules, but had a low false-positive rate and good sensitivity for detection of confirmed cancers.

The Lung Screen Uptake Trial tested a novel invitation strategy to improve uptake and reduce socioeconomic and smoking-related inequalities in lung cancer screening (LCS) participation. It provides one of the first UK-based ‘real-world’ LCS cohorts. Of 2012 invited, 1058 (52.6%) attended a ‘lung health check’. 768/996 (77.1%) in the present analysis underwent a low-dose CT scan. 92 (11.9%) and 33 (4.3%) participants had indeterminate pulmonary nodules requiring 3-month and 12-month surveillance, respectively; 36 lung cancers (4.7%) were diagnosed (median follow-up: 1044 days). 72.2% of lung cancers were stage I/II and 79.4% of non-small cell lung cancer had curative-intent treatment.

Rationale: Individuals eligible for lung cancer screening (LCS) by low-dose computed tomography (LDCT) are also at risk of chronic obstructive pulmonary disease (COPD) due to age and smoking exposure. Whether the LCS episode is useful for early detection of COPD is not well established. Objectives: To explore associations between symptoms, comorbidities, spirometry, and emphysema in participants enrolled in the Lung Screen Uptake Trial. Methods: This cross-sectional study was a prespecified analysis nested within Lung Screen Uptake Trial, which was a randomized study testing the impact of differing invitation materials on attendance of 60- to 75-year-old smokers and ex-smokers to a “lung health check” between November 2015 and July 2017. Participants with a smoking history ≥30 pack-years and who quit ≤15 years ago, or meeting a lung cancer risk of ≥1.51% via the Prostate Lung Colorectal Ovarian model or ≥2.5% via the Liverpool Lung Project model, were offered LDCT. COPD was defined and classified according to the GOLD (Global Initiative for Obstructive Lung Disease) criteria using prebronchodilator spirometry. Analyses included the use of descriptive statistics, chi-square tests to examine group differences, and univariable and multivariable logistic regression to explore associations between symptom prevalence, airflow limitation, and visually graded emphysema. Results: A total of 560 of 986 individuals included in the analysis (57%) had prebronchodilator spirometry consistent with COPD; 67% did not have a prior history of COPD and were termed “undiagnosed.” Emphysema prevalence in those with known and “undiagnosed” COPD was 73% and 68%, respectively. A total of 32% of those with “undiagnosed COPD” had no emphysema on LDCT. Inhaler use and symptoms were more common in the “known” than the “undiagnosed” COPD group (63% vs. 33% with persistent cough [P

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Introduction and objectives The success of lung cancer screening (LCS) with low-dose CT (LDCT) depends critically on delivering timely, accurate radiology reports. Its anticipated widespread introduction will place a significant burden on current thoracic radiologist capacity, mandating innovative solutions. We explored the role that trained radiographers, using computer-assisted nodule detection (CADe) software, might have in LCS reporting pathways. Methods 770 LDCTs performed as part of the Lung Screen Uptake trial (LSUT) were retrospectively reported by two radiographers (R1 and R2) using the Veolity™ CADe software. Radiographers could request the opinion of the study radiologist about uncertain findings. The original radiologists’ reports (read without CADe) were considered the reference standard. Studies were categorised as ‘positive’ (nodule or mass requiring nodule surveillance or MDT referral), ‘negative’ (no intrapulmonary findings requiring further imaging) or ‘ill-defined’ (indistinct focal abnormality requiring surveillance, e.g. consolidation). Reported outcomes were compared to the reference standard, with any discrepant (i.e. radiographer-only reported) nodules re-reviewed by both study radiologist and a second independent radiologist, and verified as either ‘true’ or ‘false positive’ (figure 1). Secondary outcomes included scan-reading times and identification of incidental findings. Results The reference standard dataset included 163 ‘positive’, 35 ‘ill-defined’, and 572 ‘negative’ studies, and 34 confirmed lung cancers. R1 and R2 requested radiologist confirmation for 6.5% and 10.4% of studies respectively. Following verification of discrepant nodules, reporting sensitivity varied significantly between radiographers at 67.3% (R1) and 74.0% (R2) for all ‘positive’ studies (OR 2.27, p=0.03): 77.4% and 93.9% for confirmed cancers. The majority of ‘missed’ lesions arose from inappropriate rejection of CADe-detected findings rather than being missed altogether. The radiographer plus CADe reading combination highlighted ten nodules previously dismissed by the study radiologist, that were subsequently recalled for further surveillance. Allowing for these, the rates of false positive reporting were 7.9% (R1) and 6.2% (R2). Conclusions Individual performance varied significantly between the two radiographers, but the overall results suggest inadequate sensitivity to recommend this strategy. As per previous observations elsewhere, using CADe software in LCS reporting pathways is likely to reduce reporting times whilst increasing reader sensitivity.

Background Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. Methods LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). Results 1568 participants were randomised during 2007–2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75–1.95) or 0.82 (95% CI 0.52–1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. Conclusions Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening., While low-dose CT is now preferred for lung cancer screening, our randomised trial of smokers with COPD showed that a proposed sequential policy using sputum testing to select who receives low-dose CT and autofluorescence bronchoscopy was ineffective http://bit.ly/2JZujnx

Introduction: Target populations for lung cancer screening by Low-Dose CT (LDCT) share common risk factors for some Interstitial Lung Diseases (ILDs) including Idiopathic Pulmonary Fibrosis (IPF) such as smoking history and advancing age. Here we report ILD cases identified within the Lung Screen Uptake Trial, a UK based dual centre LDCT lung cancer screening demonstration pilot in a population with high levels of socioeconomic deprivation. Methods: High-risk patients aged 60 to 75 were invited to a ‘lung health check appointment’. Those attending were offered a LDCT if they met the required threshold of lung cancer risk. Scans were reported by thoracic radiologists. ILD findings were classified as IPF-like or non-IPF like, as well as rated according to severity. We performed univariate analysis to determine the relationship of known ILD-risk factors and prevalence of ILD-like findings. Results: 770 individuals underwent a baseline screening LDCT. 54 (6.9%) showed features of ILD (Tab 1). Male gender was the only significantly associated predictor for the presence of radiological ILD (Tab 2). Conclusion: Prevalence of IPF like pattern in this cohort with high lung cancer risk is increased compared to published aged-matched population data (

Introduction Lung Cancer screening by Low-Dose CT (LDCT) has been shown to reduce mortality, though exactly how best to implement this is unclear. Uptake to screening trials has generally been low, particularly in those at highest risk of lung cancer. The Lung Screen Uptake Trial is a UK based dual centre LDCT randomised controlled screening trial of a modified invitation strategy versus a standard approach in a population with high levels of socioeconomic deprivation. Methods Patients were identified as ‘high-risk’ primarily by age and smoking history on a predesigned EMIS-Web search and subsequently invited on behalf of their general practitioner (GP) to a ‘lung health check’ appointment. Those attending were offered enrolment into the study and a LDCT if they met the required threshold of lung cancer risk. This abstract focuses on the mode of recruitment via general practice. Results Potentially eligible participants were recruited from 16 GP surgeries serving a population of 1 55 034. Of these, 8.7% were in the required age range of 60–75% and 98.9% of those had smoking status recorded. A mean of 32.2% (SD 3.8) of those aged 60–75 had been recorded as a current smoker in the preceding 15 years. A total of 1997 patients, who had been recorded as current smokers within the past 5 years were invited. Uptake to the study was 50.3% (n=1005) of all those invited. 765 underwent a LDCT examination (figure 1). In 10.3% of patients the smoking history was confirmed to be too light for CT screening, despite GP records suggesting otherwise. Conclusions Smoking status was found to be very well recorded in primary care records, providing a feasible method for initial selection of those eligible for screening. However we also showed the importance of confirmation of smoking history, something that might be done prior to invitation in screening programmes. This study observed a high rate of attendance when compared to previous LDCT screening trials. The explanation for this observed difference is likely to be multifactorial, though one key factor, unique to this study, is that the invitation to participate came from patients’ own GP.

Introduction Lung cancer screening by Low-Dose CT (LDCT) has been shown to reduce mortality, and the harm-benefit balance of screening is optimised by screening those at higher risk. The Lung Screen Uptake Trial is a UK based randomised controlled trial of standard versus enhanced invitation methods for LDCT screening in more deprived communities. Methods Patients aged 60 to 75, at higher risk of lung cancer by virtue of their recorded smoking history, were invited to a ‘lung health check appointment’ on behalf of their GP. Attendees at one of two secondary care sites, underwent a nurse consultation that included a lung cancer risk assessment. Participants were eligible for LDCT if they met any of the following three criteria: NLST-like criteria* (≥30 pack-year smoking history and given up ≤15 years ago); PLCO m2012 score ≥1.51%; or LLP score ≥2.5%. This abstract focuses on the performance of the different eligibility criteria. Results At the time of analysis, 1997 individuals had been invited to screening and 936 attended and were enrolled into the study. 854 participants were eligible for LDCT by fulfilling any of the 3 criteria above, and 718 went on to have LDCT. The mean age of participants was 66.0 (SD 4.16), 54.4% were male and the mean smoking pack-year history was 39.7 (SD 24.9). After a median of 9.7 months follow up, 17 lung cancers were confirmed. Ten suspicious pulmonary nodules are undergoing diagnostic work up under the lung cancer multidisciplinary team (MDT) and 80 indeterminate nodules are under CT surveillance. The distribution of these cancers and nodules by eligibility criteria is shown in Table 1. Conclusions Using the NLST-like* criteria to determine eligibility would mean the fewest number screened, with 4 fewer cancers detected. The PLCO m2012 score was the most reliable way to detect cancers and resulted in less individuals screened than with use of the LLP score. Further follow up and review of the data is required to fully establish the most effective tool for determining eligibility into LDCT screening though the PLCO m2012 score shows the most promise with the available data.

Background: The impact of the introduction of Endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) on the use of diagnostic modalities for tissue acquisition in patients with lung cancer is unknown. Methods: A retrospective review of 328 consecutive patients diagnosed with lung cancer at a university teaching hospital, where they first presented in London in 2007, 2009 and 2011. EBUS was introduced in 2008. Results: In total, 316 patients were included in the analysis. Comparing 2007 with 2011 data, there has been a significant reduction in standard bronchoscopy (P < 0.0001) and mediastinoscopy (P = 0.02). The proportion of cases diagnosed by EBUS-TBNA significantly increased from 0% in 2007 to 26.7% in 2009 and 25.4% in 2011 (P < 0.0001). In the same period there has also been an increased trend in the proportion of patients going directly to surgery without pathological confirmation with a 9.6% increase in diagnoses obtained at thoracotomy (P = 0.0526). Conclusions: The use of diagnostic modalities that provide information on diagnosis and staging in a single intervention are increasing. At our hospital, the use of EBUS-TBNA for providing a lung cancer diagnosis is increasing and this has led to a significant reduction in standard bronchoscopies and mediastinoscopies. These changes in practice may have implications for future service provision, training and commissioning.

Patients with isolated mediastinal lymphadenopathy (IML) are a common presentation to physicians, and mediastinoscopy is traditionally considered the "gold standard" investigation when a pathological diagnosis is required. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as an alternative to mediastinoscopy in patients with lung cancer.To determine the efficacy and health care costs of EBUS-TBNA as an alternative initial investigation to mediastinoscopy in patients with isolated IML.Prospective multicenter single-arm clinical trial of 77 consecutive patients with IML from 5 centers between April 2009 and March 2011. All patients underwent EBUS-TBNA. If EBUS-TBNA did not provide a diagnosis, then participants underwent mediastinoscopy.EBUS-TBNA prevented 87% of mediastinoscopies (95% confidence interval [CI], 77-94%; P0.001) but failed to provide a diagnosis in 10 patients (13%), all of whom underwent mediastinoscopy. The sensitivity and negative predictive value of EBUS-TBNA in patients with IML were 92% (95% CI, 83-95%) and 40% (95% CI, 12-74%), respectively. One patient developed a lower respiratory tract infection after EBUS-TBNA, requiring inpatient admission. The cost of the EBUS-TBNA procedure per patient was £1,382 ($2,190). The mean cost of the EBUS-TBNA strategy was £1,892 ($2,998) per patient, whereas a strategy of mediastinoscopy alone was significantly more costly at £3,228 ($5,115) per patient (P0.001). The EBUS-TBNA strategy is less costly than mediastinoscopy if the cost per EBUS-TBNA procedure is less than £2,718 ($4,307) per patient.EBUS-TBNA is a safe, highly sensitive, and cost-saving initial investigation in patients with IML. Clinical trial registered with ClinicalTrials.gov (NCT00932854).

ObjectiveThe gene coding for C-reactive protein (CRP) is located on chromosome 1q23.2, which falls within a linkage region thought to harbor a systemic lupus erythematosus (SLE) susceptibility gene. Recently, 2 single-nucleotide polymorphisms (SNP) in the CRP gene (+838, +2043) have been shown to be associated with CRP concentrations and/or SLE risk in a British family-based cohort. Our study was done to confirm the reported association in an independent population-based case-control cohort, and also to investigate the influence of 3 additional CRP tagSNP (−861, −390, +90) on SLE risk and serum CRP concentrations.MethodsDNA from 337 Caucasian women who met the American College of Rheumatology criteria for definite (n = 324) or probable (n = 13) SLE and 448 Caucasian healthy female controls was genotyped for 5 CRP tagSNP (−861, −390, +90, +838, +2043). Genotyping was performed using restriction fragment length polymorphism-polymerase chain reaction, pyrosequencing, or TaqMan assays. Serum CRP levels were measured using ELISA. Association studies were performed using the chi-squared distribution, Z-test, Fisher’s exact test, and analysis of variance. Haplotype analysis was performed using EH software and the haplo.stats package in R 2.1.2.ResultsWhile none of the SNP were found to be associated with SLE risk individually, there was an association with the 5 SNP haplotypes (p < 0.001). Three SNP (−861, −390, +90) were found to significantly influence serum CRP level in SLE cases, both independently and as haplotypes.ConclusionOur data suggest that unique haplotype combinations in the CRP gene may modify the risk of developing SLE and influence circulating CRP levels.

Summary In2001,referencetotheuseofimagingintheBritishCommittee for Standards in Haematology guidelines for the diagnosis and management of myeloma was confined to the standard use of plain X-rays in the diagnostic skeletal survey and emergency use of computed tomography (CT) and magnetic resonance (MR) imaginginthesettingofcordcompression.Sincethen,therehas been a steady rise in interest in the use of various imaging techniques in the management of myeloma. The purpose of imaginginthemanagementofmyelomaincludestheassessment of the extent and severity of the disease at presentation, the identification and characterisation of complications, and the assessment of response to therapy. Plain radiography, CT, and MRimagingaregenerallyestablishedexaminationtechniquesin myeloma whilst positron emission tomography (PET) and 99 Technetium sestamibi (MIBI) imaging are promising newer scanning techniques under current evaluation. These standalone imaging guidelines discuss recommendations for the use of each modality of imaging at diagnosis and in the follow up of patients with myeloma.

Interferon regulatory factor 5 (IRF5) belongs to a family of transcription factors that control the transactivation of type I interferon system-related genes, as well as the expression of several other genes involved in immune response, cell signalling, cell cycle control and apoptosis. Two recent studies reported a significant association between the IRF5/rs2004640 T allele and systemic lupus erythematosus (SLE). The purpose of this study was to determine whether the reported rs2004640 T allele association could be replicated in our independent SLE case-control sample. We genotyped DNA samples from 370 white SLE-affected female subjects and 462 white healthy female controls using the TaqMan Assay-on-Demand for rs2004640, and performed a case-control genetic association analysis. Frequency of the rs2004640 T allele was significantly higher in cases than in controls (56.5% vs. 50%; P= 0.008). The odds ratio for T allele carriers was 1.68 (95% CI: 1.20 - 2.34; P= 0.003). Our results in an independent case-control sample confirm the robust association of the IRF5/rs2004640 T allele with SLE risk, and further support the relevance of the type I interferon system in the pathogenesis of SLE and autoimmunity.

A 36 year old man presented with weight loss, cough, fever, and exertional dyspnoea shortly after a diagnosis of HIV infection. Symptoms and initial radiological abnormalities worsened after highly active antiretroviral therapy was started. An eventual diagnosis was established but multiple problems occurred throughout the treatment period. Differentiation between immune reconstitution inflammatory syndrome and an infective cause was problematic.

Objective Complement-activation product C4d is deposited on normal erythrocytes, while abnormal levels have been observed on the surface of erythrocytes of patients with systemic lupus erythematosus (SLE). This study examines whether C4d also deposits on human platelet surfaces, and whether platelet-bound C4d may provide a biomarker for SLE. Methods We conducted a cross-sectional study of 105 patients with SLE, 115 patients with other diseases, and 100 healthy controls. Levels of C4d on the surface of platelets were examined by flow cytometry and scanning confocal microscopy. Statistical analyses were performed to determine the clinical variables associated with platelet C4d. Results Abnormal levels of platelet C4d were found to be highly specific for SLE. Platelet C4d was detected in 18% of patients with SLE, being 100% specific for a diagnosis of SLE compared with healthy controls and 98% specific for SLE compared with patients with other diseases (P < 0.0001). In addition, platelet C4d was significantly associated with positivity for lupus anticoagulant (P < 0.0001) and anticardiolipin antibodies of the IgG (P = 0.035) or the IgM (P = 0.016) isotype. Platelet C4d was also significantly associated with SLE disease activity according to the SLE Disease Activity Index (P = 0.039), low serum C4 (P = 0.046), an elevated erythrocyte sedimentation rate (P = 0.006), and abnormal levels of C4d on erythrocytes (P < 0.0001). Conclusion This observation suggests that platelet-bound C4d may be a useful biomarker for SLE and may be a clue to the pathogenic mechanisms responsible for the myriad thrombotic and vascular complications of lupus associated with antiphospholipid antibodies.

AIM: To describe the computed tomography (CT) features of human immunodeficiency virus (HIV)-associated Castleman's disease.MATERIALS AND METHODS: Nine HIV-positive patients with biopsy-proven Castleman's disease were studied. Clinical and demographic data, CD4 count, histological diagnosis and human herpes type 8 (HHV8) serology or immunostaining results were recorded. CT images were reviewed independently by two radiologists.RESULTS: CT findings included splenomegaly (n = 7) and peripheral lymph node enlargement (axillary n = 8, inguinal n = 4). All nodes displayed mild to avid enhancement after intravenous administration of contrast material. Hepatomegaly was evident in seven patients. Other features included abdominal (n = 6) and mediastinal (n = 5) lymph node enlargement and pulmonary abnormalities (n = 4). Patterns of parenchymal abnormality included bronchovascular nodularity (n = 2), consolidation (n = 1) and pleural. effusion (n = 2). On histotogical examination eight patients (spleen n = 3, lymph node n = 9, lung n = 1 bone marrow n = 1) had the plasma cell variant and one had mixed hyaline-vascular/plasma cell variant. The majority had either positive immunostaining for HHV8 or positive serology (n = 8).CONCLUSION: Common imaging features of multicentric Castleman's disease in HIV infection are hepatosplenomegaly and peripheral lymph node enlargement. Although these imaging features may suggest the diagnosis in the appropriate clinical context, they lack specificity and so biopsy is needed for diagnosis. In distinction from multicentric Castleman's disease in other populations the plasma cell variant is most commonly encountered, splenomegaly is a universal feature and there is a strong association with Kaposi's sarcoma. (C) 2004 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Introduction and objectives Chronic obstructive pulmonary disease (COPD) and emphysema are considerably under-diagnosed conditions. Low dose CT (LDCT) for lung cancer screening, if implemented, may provide an opportunity for earlier diagnosis of smoking-related conditions, in addition to lung cancer. Data gathered in a lung cancer screening demonstration pilot was analysed to look at COPD-related radiological changes and their relationship with patients’ pre-existing diagnoses, spirometry results and smoking status. The aims were to better understand these interlinked conditions and identify the potential for earlier diagnosis and management of smoking cessation interventions for these conditions. Methods Data were collected as part of the Lung Screen Uptake Trial. Smokers and recent former smokers (quit Results 275 patients responded to an invitation to attend a ‘lung health check’ in the first six months of recruitment. 149 (54.2%) had values consistent with COPD on spirometry. 106 [71.1%, (95% CI: ± 7.3%)] of these individuals were not aware of a diagnosis of COPD, and 81 (76.4%) were current smokers (Figure 1). Of the 103 individuals who had emphysema and no suspicious lesion on LDCT, 74 [71.8%, (95% CI: ± 8.7%)] were not aware of a diagnosis of COPD or emphysema. 55 (74.3%) of these were current smokers, and 33 (44.6%) had preserved spirometry (Table 1). Conclusion Our data demonstrate the considerable burden of undiagnosed COPD in at-risk groups (38.5% of all screened individuals), and show the prevalence of emphysematous change in those patients without a pre-existing, self-reported diagnosis of COPD or with preserved spirometry. Early diagnosis and CT evidence of smoking damage may provide the opportunity to co-implement supportive smoking cessation interventions, earlier medical intervention and prevention of further progression of disease through improved management of these conditions.

Carcinoma of the bronchus is the most common malignancy in the Western world. It is also the leading cause of cancer-related death accounting for 32% of all cancer deaths in males and 25% in females 1. In the USA it causes more deaths than cancers of the colon, breast and prostate combined 2. Disappointingly, in a recent UK survey of improvements in cancer survival 3, carcinoma of the bronchus showed the smallest percentage reduction in the number of deaths avoided between 1981–1990 (0.2%). This compares badly with breast (11% reduction) and melanoma (32%). The overall 5‐yr survival for lung cancer diagnosed between 1986–1990 was only 5.3% (against 66% for breast and 76% for melanoma). It is on this background that the radiologist remains actively employed in the detection, diagnosis, staging and review of this common malignancy.

Objective: To describe the range of pathology causing pleural effusions in HIV infected patients with acute respiratory episodes and to attempt to identify whether any associated radiological abnormalities enabled aetiological discrimination. Methods: Prospective study of chest radiographs of 58 consecutive HIV infected patients with pleural effusion and their microbiological, cytological, and histopathological diagnoses. Results: A specific diagnosis was made in all cases. Diagnoses were Kaposi's sarcoma, 19 patients; parapneumonic effusion, 16 patients; tuberculosis, eight patients; Pneumocystis carinii pneumonia, six patients; lymphoma, four patients; pulmonary embolus, two patients; and heart failure, aspergillus/leishmaniasis, and Cryptococcus neoformans, one case each. Most effusions (50/58) were small. Bilateral effusions were commoner in Kaposi's sarcoma (12/19) and lymphoma (3/4) than in parapneumonic effusion (3/16). Concomitant interstitial parenchymal shadowing did not aid discrimination. A combination of bilateral effusions, focal air space consolidation, intrapulmonary nodules, and/or hilar lymphadenopathy suggests Kaposi's sarcoma. Unilateral effusion with focal air space consolidation suggests parapneumonic effusion if intrapulmonary nodules are absent: if miliary nodules and/or mediastinal lymphadenopathy are detected, this suggests tuberculosis. Conclusions: A wide variety of infectious and malignant conditions cause pleural effusions in HIV infected patients, the most common cause in this group was Kaposi's sarcoma. The presence of additional radiological abnormalities such as focal air space consolidation, intrapulmonary nodules, and mediastinal lymphadenopathy aids aetiological discrimination. Key Words: pleural effusion; Kaposi's sarcoma; bacterial pneumonia; chest radiograph

Purpose: To correlate chest radiographic abnormalities with diagnoses in HIV infected patients presenting with acute respiratory symptoms and lobar or segmental consolidation. Materials and Methods: Retrospective review of chest radiographs of 53 HIV infected patients with lobar or segmental consolidation, and their microbiological and cytological diagnoses. Results: A specific diagnosis was made in 35 patients of which 12 had Pneumocystis carinii pneumonia (including four co-infections) and 23 had bacterial pneumonias (10 of these were due to Streptococcus pneumoniae and four to Mycobacterium tuberculosis ). Microbiological and cytological tests were negative in 18 patients. Non-specific radiographic features included bronchial wall thickening (79%), reticulonodular or reticular change (55%), effusions (38%) and lymphadenopathy (25%); effusions favoured a bacterial aetiology. Ten of the 12 cases with P. carinii pneumonia had upper lobe consolidation (three of these had received inhaled pentamadine). Of 13 other cases of upper lobe consolidation, eight were due to pyogenic infection and only one to M. tuberculosis alone. Conclusion: A wide variety of causative agents may produce lobar or segmental consolidation in HIV infected individuals, and the most common cause is bacterial infection. Where there is upper lobe consolidation P. carinii pneumonia should be considered in the differential diagnosis.

Patients with systemic lupus erythematosus (SLE) are at increased risk for cardiovascular (CV) disease. The aim of this study was to investigate the association between subclinical CV disease as measured by carotid intima-media thickness (IMT) and plaque using B-mode carotid ultrasound and incident CV events in a combined cohort of female patients with SLE. This was a prospective, 2-center observational study of 392 adult women with SLE and no previous CV events with a mean 8 years of follow-up. Incident CV events confirmed by clinicians were defined as angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, fatal cardiac arrest, transient ischemic attack, and cerebrovascular accident. Incident hard CV events excluded angina and transient ischemic attack. The mean age was 43.5 years, and most patients were Caucasian (77.3%). During follow-up, 38 patients had incident CV events, and 17 had incident hard CV events. Patients with incident hard CV events had higher mean carotid IMT (0.80 vs 0.64 mm, p

Screening for the early detection of lung cancers should increase the percentage of operable tumours, thus improving cure rates. A large randomised US trial showed that CT screening moderate/heavy smokers is effective but expensive, with a high false-positive rate. We designed LungSEARCH in 2006 to target screening in higher-risk subjects. Because most tumours in the UK were of squamous-histology, we hypothesised that sputum cytology plus cytometry would be an effective initial screen, only offering more intensive/expensive tests to those with abnormal sputum. Eligibility criteria were: current/former smokers (≥20 pack-years and/or smoked ≥20 years), GOLD-defined COPD, no prior cancer. Subjects were randomised to surveillance or a control group, and each followed for 5 years. Screened subjects provided sputum for central assessment, and those with abnormal results (cytology: low/high-grade squamous intraepithelial lesions, and/or cytometry: abnormal ploidy) were referred for annual low-dose CT and autofluorescence bronchoscopy (AFB) for the remainder of the trial, with diagnostic investigations when cancer suspected by abnormal CT/AFB. Sputum-negatives provided annual sputum samples only. Control subjects had a chest X-ray when they reached 5 years. Primary objective: to show a higher proportion of early stage cancers using surveillance than controls. 1568 subjects were recruited (target 1300) from GPs or chest clinics around 10 UK centres (August 2007–March 2011): 785 screened, 783 controls. Mean age 63 years; males 52%; current (56%), former (44%) smokers; mild (25%), moderate (75%) COPD; from GPs (79%). >90% screened subjects provided sputum samples in their first year. After 5 years, the overall sputum-positive rate is 33%; 30% (236/785) had a CT scan and 25% (193/785) had an AFB at any time. Of those who had a CT scan 19% (45/236) were abnormal (lung nodule(s) ≥9 mm); and of those who had AFB 3% (5/193) had severe dysplasia or worse. 79 lung cancers have been identified to date via the centres/national registry: 43 surveillance and 36 control. But awaiting staging details for 6 surveillance and 14 control cases. Preliminary results are promising: 57% (surveillance) versus 41% (controls) of cancers were diagnosed with stage I/II non-small-cell-lung cancer or limited disease small-cell-lung cancer. Final data available later in 2016.

Objectives: To describe the mode of presentation, interventions, and outcome of HIV infected patients with pulmonary embolism and a contraindication to anticoagulation, who were treated with a bird's nest filter. Methods: Retrospective review of case records and imaging department database at UCL Hospitals, London, UK. Results: Three patients had pulmonary embolism and contraindications to anticoagulation. Contraindications were concomitant intracerebral pathology in two patients (one also had bleeding from gastric Kaposi's sarcoma and the other was cognitively impaired with HIV associated dementia complex) and alcohol induced liver disease/binge drinking in the third patient. Anticoagulation was avoided by introducing a bird's nest filter into the inferior vena cava via the common femoral vein. During follow up (7, 8, and 21 months) no complications or recurrent pulmonary emboli occurred. Conclusion: The bird's nest inferior vena cava filter has a role in preventing further pulmonary emboli in HIV infected patients with contraindications to anticoagulation. Key Words: pulmonary embolism; HIV; AIDS; haemorrhage; anticoagulation

Patients with systemic lupus erythematosus (SLE) and those with rheumatoid arthritis (RA) have increased risk for atherosclerotic cardiovascular disease. The aims of this study were to compare the presence of coronary artery calcium (CAC) in age- and race-matched women with SLE, those with RA, and healthy controls without diabetes mellitus or history of myocardial infarction, angina pectoris, or stroke and to investigate its relation with traditional risk factors, inflammation, and endothelial activation. Study subjects completed cardiovascular risk factor assessment and electron-beam computed tomography that measured CAC. The 2 patient groups had similar prevalence and extent of CAC as well as significantly increased odds of having any CAC (odds ratio 1.87, 95% confidence interval 1.09 to 3.21) and more extensive CAC (odds ratio 4.04, 95% confidence interval 1.42 to 11.56 for CAC score >100) compared with healthy controls. After controlling for differences in cardiovascular risk factors, including insulin resistance and hypertension, the results remained statistically significant. After adjustment for differences in levels of C-reactive protein and/or soluble intercellular adhesion molecule–1, however, women with chronic inflammatory diseases no longer had significantly increased odds of having any CAC or more extensive CAC compared with controls. In conclusion, asymptomatic and nondiabetic women with chronic inflammatory diseases had significantly increased odds of having CAC and more extensive CAC compared with age- and race-matched healthy controls. The increased odds for CAC may in part result from higher levels of inflammation and endothelial activation in these patients.

Summary Low serum paraoxonase1 (PON1) activity determined by paraoxon substrate is associated with coronary heart disease (CHD), diabetes and systemic lupus erythematosus (SLE) risk. In this investigation, we have examined the role of genetic variation in the PON3 gene in relation to PON1 activity and SLE risk in a biracial sample comprising 377 SLE patients and 482 controls from US whites and blacks. We genotyped six PON3 tagging single nucleotide polymorphisms (tagSNPs) and examined their associations with PON1 activity, SLE risk, antiphopholipid autoantibodies (APA), lupus nephritis, carotid vascular disease, and inflammation. With the exception of PON1 activity, no other significant associations were found with PON3 SNPs. Multiple regression analysis including all six PON3 tagSNPs and PON1/Q192R and L55M SNPs revealed significant association of PON1 activity with 4 SNPs: PON3/A10340C (p < 0.0001), PON3/A2115T (p = 0.002), PON1/L55M (p < 0.0001) and PON1/Q192R (p < 0.0001). These four SNPs explained 2%, 1%, 8% and 19% of the variation in PON1 activity, respectively. In summary, our new data indicate that genetic variation in the PON3 gene influences serum PON1 activity independently of the known effect of PON1 genetic variation. To our knowledge, this is the first study reporting the association of the PON3 gene variants with PON1 activity.

In 2001, reference to the use of imaging in the British Committee for Standards in Haematology guidelines for the diagnosis and management of myeloma was confined to the standard use of plain X-rays in the diagnostic skeletal survey and emergency use of computed tomography (CT) and magnetic resonance (MR) imaging in the setting of cord compression. Since then, there has been a steady rise in interest in the use of various imaging techniques in the management of myeloma. The purpose of imaging in the management of myeloma includes the assessment of the extent and severity of the disease at presentation, the identification and characterisation of complications, and the assessment of response to therapy. Plain radiography, CT, and MR imaging are generally established examination techniques in myeloma whilst positron emission tomography (PET) and (99)Technetium sestamibi (MIBI) imaging are promising newer scanning techniques under current evaluation. These stand-alone imaging guidelines discuss recommendations for the use of each modality of imaging at diagnosis and in the follow up of patients with myeloma.

Background: The natural history of bronchial preinvasive lesions and the risk of developing lung cancer in patients with these lesions are not clear. Previous studies have treated severe dysplasia and carcinoma in situ (CIS) on the assumption that most will progress to invasive carcinoma. Aims: To define the natural history of preinvasive lesions and assess lung cancer risk in patients with these lesions. Hypothesis: Most preinvasive lesions will not progress to invasive carcinoma but patients with these lesions will be at high risk. Methods: A cohort of patients with preinvasive lesions underwent fluorescence bronchoscopy every 4–12 months and computed tomography of the chest annually. The main end point was the development of invasive carcinoma. Results: 22 patients with 53 lesions were followed up for 12–85 months. 11 cancers were diagnosed in 9 patients. Of the 36 high-grade lesions (severe dysplasia and CIS), 6 progressed to invasive cancers. 5 separate cancers developed at remote sites in patients with high-grade lesions. All cancers were N0M0 and curative treatment was given to 8 of the 9 patients. The cumulative risk of developing lung cancer in a patient with a high-grade lesion was 33% and 54% at 1 and 2 years, respectively. Of the 17 low-grade lesions, none progressed to invasive carcinoma. Conclusions: Although the risk of malignant progression of individual preinvasive lesions is relatively small, patients with high-grade lesions are at high risk of lung cancer. Surveillance facilitated early detection and treatment with curative intent in most patients.

Objective Low serum paraoxonase 1 (PON1) activity determined with paraoxon as substrate has been found to be associated with coronary artery disease. This study was undertaken to examine the relationship of PON1 activity and genotype to risk of systemic lupus erythematosus (SLE). Methods The impact of 7 PON1 single-nucleotide polymorphisms (SNPs) was analyzed in relation to PON1 activity, SLE risk, lupus nephritis, antiphospholipid antibody (aPL) positivity, and carotid vascular disease in 380 SLE patients (334 white, 46 black) and 497 controls (455 white, 42 black). Results Compared with findings in controls, PON1 activity with paraoxon substrate was reduced both in white lupus patients (mean ± SEM 618.9 ± 24.0 units/liter versus 719.6 ± 24.6 units/liter; P = 0.007) and in black lupus patients (991.1 ± 82.7 units/liter versus 1,164.3 ± 101.4 units/liter; P = 0.2711). Low PON1 activity in SLE was not associated with the occurrence of aPL, carotid vascular disease, or the use of immunosuppressive drugs. In multiple regression analyses, the Q192R SNP was found to be independently associated with PON1 activity and explained 28% and 41% of the variation in PON1 activity in white patients and black patients, respectively. Stratification of the lupus sample by presence (n = 81) or absence (n = 247) of renal disease revealed significant associations with 3 promoter SNPs, with odds ratios of 3.82 (95% confidence interval [95% CI] 1.49–9.82, P = 0.005), 3.41 (95% CI 1.35–8.61, P = 0.009), and 2.17 (95% CI 1.01–4.68, P = 0.049). Conclusion To our knowledge, this is the first study to assess the role of PON1 activity in SLE risk in a large biracial sample from the US. Our data indicate that low PON1 activity determined with paraoxon substrate is independently associated with SLE and that certain PON1 SNPs are associated with lupus nephritis.

Refractive devices used by aviators need to suit the aerospace environment or their failure can have serious implications. A relatively minor visual disability can result in loss of life and aircraft. We surveyed commonly occurring problems with the different types of refractive correction worn by Royal Air Force (RAF) aircrew over the previous 12 mo. We also asked if they had experienced any flight safety incidents (FSI) relating to their refractive correction.A retrospective anonymous questionnaire survey was given to 700 active aircrew occupationally graded as requiring corrective flying spectacles (CFS) or contact lenses (CL) for flying.63% (443) of the questionnaires were completed. CL were worn by 53% of aircrew; 71% of them used daily disposable CL. CFS were worn by the remaining 47% of aircrew, 14% of whom used multifocal lenses. Of CFS wearers, 83% reported problems including misting, moving, discomfort, and conflict with helmet-mounted devices (HMD). CL-related ocular symptoms were reported in 67% of wearers including cloudy vision, dry eye, photophobia, red eyes, excessive mucus formation, CL movement, itching, and grittiness. No CL-related FSI were reported over the previous 12 mo compared with 5% CFS-related FSI (p0.001). The graded performance of CL for vision, comfort, handling, convenience, and overall satisfaction was significantly higher than for CFS.CFS are associated with problems in terms of comfort and safety. CL are well tolerated by aircrew, and deliver improved visual performance.

A 41 year old HIV infected man with an extensive travel history developed intermittent fever and weight loss shortly after returning from abroad. Extensive and prolonged investigation identified the cause.

Introduction NICE guidance for the diagnosis and treatment of lung cancer recommends choosing “investigations that give the most information about diagnosis and staging with the least risk to the patient”. [1] EBUS-TBNA is expanding as an important diagnostic modality in lung cancer and provides simultaneous information on lung cancer phenotype, genotype and nodal staging. The impact of the introduction of EBUS-TBNA on the use of diagnostic modalities for tissue acquisition in patients with lung cancer is unknown. Methods A retrospective review of 407 consecutive patients diagnosed with lung cancer at a university teaching hospital in 2007, 2009 and 2011. Data were collected on age, gender, FEV1, performance status, diagnostic modality, and pathological subtype. Patients where only a clinical diagnosis was made (n=21) were excluded. Data were analysed using the SPSS version 17 (Chicago, IL, USA). For comparison between categorical variables, Chi-square or Fisher’s exact test were used as appropriate. All reported p -values are two-tailed, and are considered statistically significant when p Results 386 patients were included in the analysis. The mean (SD) age (years) and FEV1 (L/min) were 69 (12) and 1.81 (0.80) for 2007, 67 (10) and 1.81 (0.79) for 2009 and 68 (12) and 2.07 (0.68) for 2011 respectively. In 2007, 2009 and 2011 57.9%, 51.4% and 62.7% were males. The results on diagnostic modalities, performance status, histological subtype and staging are listed in Table 1. Comparing 2007 to 2011 there has been a significant reduction in standard bronchoscopy (P=0.0001), CT guided biopsy of peripheral lesions (P=0.0008) and mediastinoscopy (P=0.0382). The proportion of cases diagnosed by EBUS-TBNA significantly increased from 0% in 2007 to 21.4% in 2009 and 25.4% in 2011 (P Conclusions The use of diagnostic modalities that provide information on diagnosis and staging in a single intervention are increasing. At our hospital, the use of EBUS-TBNA has led to a significant reduction in CT guided biopsies, standard bronchoscopies and mediastinoscopies. These changes in practise have implications for future service provision, training and commissioning. Reference NICE Lung cancer. 2011.http://publications.nice.org.uk/lung-cancer-cg121/key-priorities-for-implementation.

Introduction Intra-thoracic lymphadenopathy is commonly observed in patients infected with HIV. The broad range of aetiologies and the non-specific clinical picture constitute a diagnostic challenge which has not been previously addressed. Therefore we aimed to identify the causes of mediastinal lymphadenopathy in HIV infected patients presenting to our specialist unit and to characterise their mode of diagnosis. Methods We conducted a retrospective analytical cohort study of HIV positive patients who underwent CT scanning of the chest between January 2004 and December 2008. Each patient was followed clinically for at least 12 months. Results 234 consecutive patients underwent chest CT in the study period. Employing the conventional CT cut-off for significant lymphadenopathy of 10 mm in short-axis, mediastinal lymphadenopathy was present in 49 (21%) patients. In these 49 patients, the mean age was 40 (range 19–69) years. 43 patients were male and 24 of the male patients were homosexual. 25 (51%) of patients were receiving antiretroviral therapy and 24 patients had a CD4 lymphocyte count below 250 cells ×106/l. A specific diagnosis was made in 42 cases. Lymphoma was the most common diagnosis with 9 cases, followed by TB with seven cases. Six patients had reactive lymphadenopathy secondary to pneumonia. There were four cases of Castleman9s disease, four of malignancy and three of non-tuberculous mycobacterial infection. In total, 13 patients (31%) were diagnosed with cancer. Extra-thoracic lymphadenopathy documented by CT was present in 26 (53%) of patients, including in seven cases of lymphoma and in all cases of Castleman9s disease. The diagnosis was established by histopathology in 57% of cases, by clinical follow-up in 19% and by microbiology in 7%. USS guided peripheral lymph node biopsy was the preferred biopsy method in 16 cases. Surgical biopsy was performed in seven cases and EBUS-TBNA in two cases. Conclusions Mediastinal lymphadenopathy is common in HIV positive patients undergoing CT scanning of the thorax and can be associated with a wide range of conditions. However, the prevalence of malignancy is high in this setting, emphasising the need for a pathological diagnosis.

Background Surgery is the treatment of choice for early stage non-small cell lung cancer (NSCLC). However, curative intent is commonly not achieved due to inaccurate clinical staging and disease recurrence. Aim We aimed to determine the incidence of futile thoracotomies (FT) in patients with NSCLC following surgery with curative intent. In addition, we wished to identify prognostic factors that predicted FT. Methods In this analytical retrospective cohort study, thoracotomy cases between October 2003 and September 2008 at a single institution were identified. Confirmed cases of primary NSCLC only were included. A thoracotomy was deemed futile if any one of the following criteria were met: pathologically confirmed N2, N3, or M1 disease, an exploratory thoracotomy, or a thoracotomy in a patient who developed recurrent disease or died within 1 year of surgery. When a PET scan was performed, the SUVmax of the primary tumour was reported by a radiologist blinded to the clinical information. Case notes and hospital systems were interrogated for evidence of recurrence and survival. Statistical analysis was performed with STATA version 10 for Windows. Results We identified 171 consecutive patients with NSCLC who underwent lung resection with curative intent. 105 (61%) were male and mean age at the time of surgery was 66 years. 134 (78%) had lobectomy, 8 bi-lobectomy, 19 pneumonectomy and 10 sub-lobar resection (segmentectomy or wedge resection). Overall 46 (27%) underwent FT. Nine patients (5.2%) had clinically unsuspected N2 disease at pathological staging. An SUVmax of the primary tumour greater than 8 was associated with an increased risk of FT (RR 2.35 (p=0.03)) (Abstract P222 Table 1). The presence of lymphovascular invasion was also associated with a increased risk of FT (RR 1.71 (p=0.04)). Those with a primary tumour greater than or equal to 3 cm in size had a RR of 1.91 (p=0.02) of FT. Conclusions Between 2003 and 2008, 27% of patients at our cardiothoracic centre for lung cancer underwent a futile thoracotomy. High SUVmax, the presence of lymphovascular invasion and tumour size ≥3 cm are predictors of FT. Future, prospective studies employing adjuvant chemotherapy in these patient groups are warranted.

OBJECTIVES: To determine the incidence, mode of presentation, and outcome of pulmonary embolism (PE) in patients with HIV infection. METHODS: Retrospective review of clinical case records, imaging department database, and necropsy reports of patients admitted to the specialist HIV/AIDS unit at UCL hospitals from April 1993 to August 1997 in order to identify those with a diagnosis of PE. RESULTS: During the study period there were 3792 admissions of whom 10 (0.26%) had PE. All patients with PE presented with fever, seven were dyspnoeic, and seven had cough: all were thought initially to have respiratory infection. Only five patients had pleural pain. All 10 patients had abnormal baseline chest radiographs. The diagnosis in six was made by computed tomograph (CT) pulmonary angiography, in two was made by ventilation perfusion (V/Q) scanning, in one by both techniques, and in one at necropsy. CT angiography in addition to identifying thrombus also showed concomitant lung parenchymal abnormalities in all but one patient. Nine patients with PE had one or more risk factors for venous thromboembolism as did 34/40 case matched controls (odds ratio = 1.67; 95% confidence interval = 0.18-15.5). All patients diagnosed in life were anticoagulated and five survived. CONCLUSIONS: PE was uncommon in this HIV infected population. The diagnosis should be considered in patients with respiratory infection which does not respond to antibiotics. Identifiable risk factors for venous thromboembolism appear to be unhelpful in increasing clinical index of suspicion for PE. As baseline chest radiographs are frequently abnormal, the diagnostic utility of V/Q scanning may be reduced and CT pulmonary angiography is the imaging modality of first choice.

Respiratory infections play an important role in the morbidity and mortality associated with autoimmune disease. A patient with autoimmune disease who presents with a fever, cough breathlessness or pleuritic pain may have a respiratory infection, but these symptoms can also occur if there is an exacerbation of the autoimmune process or adverse reaction to medication. A general approach to such a patient is outlined as an algorithm in Figure 1. A complete drug history is essential. Empirical treatment with antibiotics for common respiratory infections (e.g. a penicillin and a macrolide), while awaiting the results of blood cultures, sputum examination and serology, will cover the majority of such episodes. Patients with low numbers of circulating neutrophils or lymphocytes require special consideration. High-resolution computed tomography (CT) may reveal parenchymal lesions where the chest radiograph appears normal, such as ground-glass shadowing with Pneumocystis carinii pneumonia (PCP), nodules with Aspergillus or an early drug reaction, or may be diagnostic, e.g. the “halo sign” in Aspergillus infection. A more invasive approach is dictated by a lack of response to treatment, and again CT is valuable in planning the procedure and anatomical site to be sampled. The choice of bronchoscopy, thoracoscopy or open-lung biopsy is determined by the patient’s condition: rapid worsening of the patient’s clinical state or hypoxia recommend an open-lung biopsy. Transbronchial biopsies are frequently too small to provide adequate material to make a diagnosis, and there is a greater risk to the patient who is approaching respiratory failure from pneumothorax and haemorrhage.

We report the pulmonary computed tomography (CT) findings in three patients with acute promyelocytic leukaemia who developed the retinoic acid syndrome following all-trans retinoic acid (ATRA) therapy. The most consistent CT findings were small, irregular peripheral nodules in the lung fields and pleural effusions. Two of the patients also showed evidence of reticular and ground glass shadowing as well as abnormal anterior mediastinal soft tissue. We report for the first time an association between ATRA and pneumothorax. We conclude that routine CT scanning may provide a sensitive means of early detection or monitoring of the syndrome and thereby may facilitate its management.

Caulobacter crescentus carries a flagellum and is motile only during a limited time in its cell cycle. We have asked if the biochemical machinery that mediates chemotaxis exists coincident with the cell's structural ability to respond to a chemotactic signal. We first demonstrated that one function of the chemotaxis machinery, the ability to methylate the carboxyl side chains of a specific set of membrane proteins (methyl-accepting chemotaxis proteins, MCPs), is present in C. crescentus. This conclusion is based on the observations that (i) methionine auxotrophs starved of methionine can swim only in the forward direction (comparable to smooth swimming in the enteric bacteria), (ii) a specific set of membrane proteins was found to be methylated in vivo and the incorporated [3H]methyl groups were alkali sensitive, (iii) this same set of membrane proteins incorporated methyl groups from S-adenosylmethionine in vitro, and (iv) out of a total of eight generally nonchemotactic mutants, two were found to swim only in a forward direction and one of these lacked methyltransferase activity. Analysis of in vivo and in vitro methylation in synchronized cultures showed that the methylation reaction is lost when the flagellated swarmer cell differentiates into a stalked cell. In vivo methylation reappeared coincident with the biogenesis of the flagellum just prior to cell division. In vitro reconstitution experiments with heterologous cell fractions from different cell types showed that swarmer cells contain methyltransferase and their membranes can be methylated. However, newly differentiated stalked cells lack methyltransferase activity and membranes from these cells cannot accept methyl groups. These results demonstrate that MCP methylation is confined to that portion of the cell cycle when flagella are present.

Streptomyces lividans 66 was transformed with a plasmid containing the regulatory region of the Streptomyces fradiae aph gene and a structural gene that specifies bovine growth hormone (bGH). When grown in liquid culture the transformant contained a protein identical to authentic bGH, as judged by radioimmunoassay and immuno-blotting (Western analysis). The bGH was present in cells that had been in culture for up to four weeks but was not found in the medium. The strategy employed should be generally applicable to the expression of foreign genes in actinomycetes.