Towards an understanding of the nature of resistance to Phytophthora root rot in red raspberry.

A mapping population segregating for root rot resistance was screened under both field and glasshouse conditions over a number of seasons. Few correlations between field and glasshouse scores were significant. Final root rot scores were significantly negatively correlated with measures of root vigour. Two QTL associated with resistance were identified as were overlapping QTL for root vigour assessments. Markers significantly associated with the traits were used to identify BAC clones, which were subsequently sequenced to examine gene content. A number of genes were identified including those associated with stem cell identity, cell proliferation and elongation in the root zone, control of meristematic activity and organisation, cell signalling, stress response, sugar sensing and control of gene expression as well as a range of transcription factors including those known to be associated with defence. For marker-assisted breeding, the SSR marker Rub118b 110 bp allele from Latham was found in resistant germplasm but was not found in any of the susceptible germplasm tested.

Long-term macrolide therapy in chronic inflammatory airway diseases.

In addition to direct antibacterial actions, 14- and 15-member-ring macrolides have immune modulating effects that appear to be the reason for clinical benefit in diffuse panbronchiolitis. A literature search was conducted for studies of the clinical effectiveness of macrolides in other chronic lung conditions. A number of studies were identified that showed short-term beneficial outcomes or the potential for such outcomes in cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, asthma and post-transplant obliterative bronchiolitis. The studies were limited by small patient numbers, different outcome measures and short-term follow-up, and were not designed to assess potentially harmful effects. Further large prospective and long-term studies are required in order to identify potential benefit and harm before these agents can be recommended routinely for these conditions.

Presumed tuberculosis-associated uveitis: rising incidence and widening criteria for diagnosis in a non-endemic area.

PurposeTo assess the incidence, clinical ocular involvement and effectiveness of anti-tuberculous treatment in patients with chronic uveitis presumed to be associated with tuberculosis in a non-endemic community.Patients and methodsRetrospective case series of patients with uveitis and evidence of tuberculosis, with no other identified cause of uveitis, who underwent a 6-month course of standard anti-tuberculosis treatment between 2008 and 2015. The response to treatment was assessed at 6 and 12 months after initiation of treatment.ResultsForty-eight patients were included of whom 36 (75%) were born outside the United Kingdom. Only five had concurrent active pulmonary or nodal tuberculosis. There were 85 affected eyes, including 25 with granulomatous anterior uveitis, 32 with retinal vasculitis (occlusive in 21), and 20 with multifocal choroiditis or serpiginous-like retinochoroiditis. Gamma-interferon testing was positive in 95%. Complete resolution at end point was seen in only 60%, but a further 19% were inflammation-free on topical steroid only. Resolution was lower (50%) in those with panuveitis compared to other anatomical types (75%). Sixty-four eyes (75%) had a LogMAR visual acuity of 0.1 or better at the end of the study.ConclusionsThe incidence of presumed tuberculosis-associated uveitis (TBU) has almost quadrupled in this region. The efficacy of treatment has not been enhanced by the introduction of gamma-interferon testing to support diagnosis. Some patients may require more prolonged antibiotic therapy to ensure quiescence, but chronic non-infective anterior uveitis may in any case follow treated TBU.

Investigation of a tuberculosis cluster at a job centre in Manchester, United Kingdom.

During the summer of 2005, four cases of active tuberculosis from the same occupational setting were investigated in Manchester, UK. The index case had been diagnosed in December of the previous year. At that stage the closest occupational contacts had been screened, all of whom were assessed as being free from active disease, and none had met nationally recommended criteria for chemoprophylaxis for latent tuberculosis infection (LTBI). In June 2005, two work contacts developed progressive primary extrapulmonary (pleural) TB. Following a detailed risk assessment, the screening programme was widened to include 137 staff who worked at the job centre (employment agency) where the first four cases had been found. This screening programme was based on tuberculin Mantoux testing, CXR and gamma-interferon testing. Of these 137 contacts screened, one additional person was found to have active disease and six others were offered chemoprophylaxis for LTBI. The isolates from the index case and the first two secondary cases were indistinguishable on VNTR-MIRU (variable number tandem repeat - mycobacterial interspersed repetitive unit) typing at 15 loci. No samples were available for testing from the fourth case of active disease. Management of this incident has benefited from the evolving fields of both genotyping and diagnostic testing for LTBI. However, further research into the epidemiological inferences made through genotyping, as well as the significance of a positive gamma-interferon test in assessing the risk of development of active disease, is still required.

Investigation of a tuberculosis cluster at a job centre in Manchester, United Kingdom.

During the summer of 2005, four cases of active tuberculosis from the same occupational setting were investigated in Manchester, UK. The index case had been diagnosed in December of the previous year. At that stage the closest occupational contacts had been screened, all of whom were assessed as being free from active disease, and none had met nationally recommended criteria for chemoprophylaxis for latent tuberculosis infection (LTBI). In June 2005, two work contacts developed progressive primary extrapulmonary (pleural) TB. Following a detailed risk assessment, the screening programme was widened to include 137 staff who worked at the job centre (employment agency) where the first four cases had been found. This screening programme was based on tuberculin Mantoux testing, CXR and gamma-interferon testing. Of these 137 contacts screened, one additional person was found to have active disease and six others were offered chemoprophylaxis for LTBI. The isolates from the index case and the first two secondary cases were indistinguishable on VNTR-MIRU (variable number tandem repeat--mycobacterial interspersed repetitive unit) typing at 15 loci. No samples were available for testing from the fourth case of active disease. Management of this incident has benefited from the evolving fields of both genotyping and diagnostic testing for LTBI. However, further research into the epidemiological inferences made through genotyping, as well as the significance of a positive gamma-interferon test in assessing the risk of development of active disease, is still required.

Equitable tuberculosis care in the North West of England: analysis of tuberculosis cohort review data.

BACKGROUND: In the United Kingdom, tuberculosis (TB) predominantly affects the most deprived populations, yet the extent to which deprivation affects TB care outcomes is unknown. METHODS: Since 2011, the North West TB Cohort Audit collaboration has undertaken quarterly reviews of outcomes against consensus-defined care standard indicators for all individuals notified with TB. We investigated associations between adverse TB care outcomes and Index of Multiple Deprivation (IMD) 2010 scores measured at lower super output area of residence using logistic regression models. RESULTS: Of 1831 individuals notified with TB between 2011 and 2014, 62% (1131/1831) came from the most deprived national quintile areas. In single variable analysis, greater deprivation was significantly associated with increased likelihood of the completion of a standardised risk assessment (OR 2.99, 95%CI 5.27-19.65) and offer of a human immunodeficiency virus test (OR 1.72, 95%CI 1.10-2.62). In multivariable analysis, there were no significant associations. CONCLUSIONS: TB patients in the most deprived areas had similar care indicators across a range of standards to those of individuals living in the more affluent areas, suggesting that the delivery of TB care in the North West of England is equitable. The extent to which the cohort review process contributes to, and sustains, this standard of care deserves further study.

Chemotherapy with vincristine/ifosfamide/carboplatin/etoposide in small cell lung cancer.

Although chemotherapy is considered the cornerstone of treatment for small cell lung cancer (SCLC), the majority of SCLC patients relapse and die of their disease within 2 years of diagnosis. Until newer, more effective drugs are developed, both optimization of available chemotherapeutic regimens and the use of combined chemotherapy/radiotherapy will be required to improve the survival of SCLC patients. Combining ifosfamide, carboplatin, and etoposide, among the most active single agents against SCLC, into the ICE regimen was a logical move that has resulted in improved response and survival rates. In limited and extensive SCLC, respectively, ICE and ICE administered with vincristine (VICE) have achieved overall response rates of 79% to 94% and 77% to 100% and 2-year survival rates of 24% to 33% and 9% to 25%, respectively. Treatment-related toxicities, especially myelosuppression, have hindered efforts to accelerate the administration of ICE and VICE regimens and to incorporate them into combined-modality treatments. However, the use of hematologic support measures, including growth factors and peripheral blood progenitor cells, may pave the way for maximizing the effectiveness of these regimens.

Practical considerations and guidelines for the management of community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a common condition which has a significant mortality. The management of a patient with CAP is centred around assessment and correction of gas exchange and fluid balance together with administration of appropriate antibiotics. Up to 10 different pathogens regularly cause CAP, of which Streptococcus pneumoniae is the most important. These different pathogens cannot be distinguished by clinical features or simple laboratory tests. Microbiological tests are slow and insensitive, so empirical therapy is necessary, at least initially. Accurate assessment of illness severity is the most important factor determining initial management, since this assists the decision of whether to admit the patient to hospital in addition to guiding antibiotic choice and route of administration. Two different approaches to severity assessment are outlined. Our antibiotic recommendation for empirical therapy for the patient managed at home and the previously fit patient admitted to hospital is amoxicillin. Amoxicillin/clavulanate plus a macrolide is our choice for the severely ill previously fit patient and a third-generation cephalosporin plus a macrolide is recommended for the severely ill patient with comorbidity. Alternative pathogens and specific treatment regimens are also described. There may be several causes of treatment failure, and in patients who fail to respond to therapy, it is essential to review all the initial clinical and laboratory information, which if necessary must be repeated.

Community-acquired pneumonia guidelines--an international comparison: a view from Europe.

Following an outline that details the pathogens causing community-acquired pneumonia (CAP) identified in studies from Europe, this article reviews the guidelines for the management of CAP in four European countries--France, Italy, Spain, and the United Kingdom. The method behind the development of each document is described, followed by a comparison of the scope of each document. All four documents provide guidelines for the management of two groups of patients--the severely ill and the nonseverely ill patient. A penicillin or macrolide feature for the nonseverely ill and the combination of a third-generation cephalosporin plus a macrolide for the severely ill patient are described in all four guidelines. Despite their different origins and methods, these four guidelines have more similarities than differences--the latter serving to emphasize some of the areas that require further research in this important condition. An important area for research is the impact that these guidelines have on practice and especially on clinical outcomes.

The isolation of genomic DNA from blackcurrant (Ribes nigrum L.).

A method is described for isolating DNA of high molecular mass (M(r)) from blackcurrant and other softfruit species. Following a hexacethylytimethyl ammonium bromide (CTAB)-based extraction procedure, samples are treated with a glycosidic hydrolase mixture and RNase, and then purified. The suitability of this DNA for Southern analysis and genomic-library construction is demonstrated.

Isolation of RNA from blackcurrant (Ribes nigrum L.) fruit.

Extraction of high-quality RNA from blackcurrant fruit has hitherto proved difficult, probably owing to high levels of phenolic and polysaccharide components in the berries. The procedure described here is a modification of one described for grape berries, and yields RNA suitable for in vitro translations, RNA blot analysis, and cDNA library construction.

The isolation of RNA from raspberry (Rubus idaeus) fruit.

Previous attempts to extract high-quality, total RNA from raspberry (Rubus idaeus) fruits using published protocols have proven to be unsuccessful. Even the use of protocols developed for the extraction of RNA from other fruit tissue has resulted in low yields (1) or the isolation of degraded RNA (2). Here, we report on the development of a quick and simple method of extracting total RNA from raspberry fruit. Using this method, high yields of good quality, undegraded RNA were obtained from fruit at all stages of ripening. The RNA is of sufficient quality for northern analysis and cDNA library construction.

Rheumatoid arthritis and cryptogenic organising pneumonitis.

We describe three patients with rheumatoid arthritis who presented with non-specific pulmonary symptoms, a restrictive defect in lung function and bilateral changes on chest radiograph. Lung histology showed characteristic features of cryptogenic organising pneumonitis and treatment with steroids produced significant improvement. The clinical and laboratory features of cryptogenic organising pneumonitis (otherwise known as bronchiolitis obliterans organising pneumonia, 'BOOP') are discussed and compared with those of bronchiolitis obliterans with which the condition should not be confused. Cryptogenic organising pneumonitis should be considered as one of the pulmonary manifestations of rheumatoid arthritis, but lung biopsy is essential to make the diagnosis.

The value of routine microbial investigation in community-acquired pneumonia.

The way in which microbiological investigations are used in routine clinical practice and the value of such tests in directing antibiotic prescribing, was studied in adults admitted to hospital with a diagnosis of community-acquired pneumonia. One-hundred and twenty-two consecutive patients admitted to one teaching and one district general hospital were studied between April 1988 and March 1989. Blood cultures were performed in 81% of cases, sputum was examined in 45% and complete serological tests were performed in 28%. No causative pathogen was found in 74% of cases and results of microbial tests directed a change in antibiotic therapy in only 8% of cases. Routine microbial investigation of all adults admitted to hospital with community-acquired pneumonia is unhelpful and probably unnecessary. We suggest a strategy for microbial investigation linked to initial illness severity to replace the current haphazard approach.