Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila genome

A 22-kb DNA locus of Legionella pneumophila is described that contains 18 genes, 16 of which are required for macrophage killing (icm genes). In this paper two previously described icm loci were linked by the discovery of five genes located between the two loci. Four of the newly described genes are required for macrophage killing (icmMLKE) and one is dispensable. The 16 icm genes appeared to be organized as six individual genes (icmR, icmQ, icmG, icmC, icmD, and icmF), and four operons (icmTS, icmPO, icmMLKE, and icmJB). Four icm genes (icmP, icmO, icmL, and icmE) show significant sequence similarity to plasmid genes involved in conjugation, whereas the other icm genes were found not to bear any sequence similarity to database entries. We found that L. pneumophila can mediate plasmid DNA transfer at a frequency of 10⁻³ to 10⁻⁴ per donor. Strains containing null mutations in two icm genes (icmT and icmR) showed a severe reduction in conjugation frequency and macrophage killing. Strains containing an insertion in four other icm genes (icmF, icmE, icmC, and dotA) were shown to have a less severe defect in conjugation. Mutations in the other 11 icm genes had no effect on conjugation frequency. We currently do not know whether conjugation itself plays a role in macrophage killing. It is possible either that small plasmids can take advantage of an existing secretion system to be mobilized or that DNA transfer is required for human macrophage killing by L. pneumophila.     

The role of occupational and environmental exposures in the aetiology of acquired severe aplastic anaemia: a case control investigation

Aplastic anaemia is a rare but serious disorder with a high morbidity and mortality rate. The causes of aplastic anaemia are, for the most part, unknown. We report on the hypothesis that aplastic anaemia may be caused by occupational and/or environmental exposures to certain chemicals. The UK Aplastic Anaemia Study was an interview-based case-control study covering the whole of Great Britain. Those patients diagnosed between 1 July 1993 and 20 October 1997, aged < or =75 years and born and diagnosed in the UK were eligible for the study. Two hundred eligible cases of aplastic anaemia were compared with 387 age- and sex-matched controls. A number of occupational exposures showed increases in risk. In a multivariate model of these exposures the odds ratios (ORs) for solvents/degreasing agents, pesticides and radiation were >2 and statistically significant. Reported chemical treatment of houses within 5 years of diagnosis had a significantly raised risk for adults [OR = 2.51, 95% confidence interval (CI) 1.02-12.01], particularly for woodworm treatment (OR = 5.1, 95% CI 1.5-17.4). This study identified significant risks associated with self-reported exposure to solvents, radiation and pesticides in the workplace. Self-reported chemical treatment of houses was also associated with an increased risk of developing aplastic anaemia, in keeping with previous literature.     

Molecular markers in prognosis of colorectal cancer and prediction of response to treatment

Colorectal cancer is the third most common human malignancy. Direct observation and biopsy sampling by colonoscopy have provided unique opportunities to study the natural history of the disease. As a consequence, advances in the understanding of colorectal cancer pathogenesis have evolved more rapidly than with most other solid tumours. Numerous molecular events arising during the development of colorectal cancer have been sorted out over the past two decades. Despite these advances, predicting outcome and response to therapy is still a major challenge in the management of patients with colorectal cancer. Molecular and biochemical markers of colorectal cancer are greatly needed for diagnosis and prognosis as well as for the selection and monitoring of treatments. The purpose of this chapter is to provide a critical assessment of the usefulness of markers in the prognosis and prediction of response to treatment in colorectal cancer.     

Women With Cardiogenic Shock Derive Greater Benefit From Early Mechanical Circulatory Support: An Update From the cVAD Registry

Objectives

The aim of this analysis was to assess survival differences between men and women supported with Impella 2.5 (Abiomed Inc., Danvers) in the setting of acute myocardial infarction (AMI) complicated by cardiogenic shock (CS).

Background

Data on sex differences in outcomes of CS with mechanical circulatory support are sparse.

Methods

Patients enrolled in the cVAD Registry who underwent percutaneous coronary intervention (PCI) and Impella 2.5 support for CS complicating an AMI were included. Differences between men and women were examined.

Results

In total, 180 patients were analyzed. Women (n = 49, 27.2%) were older (71.0 ± 12.8 years vs 63.8 ± 13.0, P = 0.001), smaller (BSA 1.82 ± 0.22 vs 2.04 ± 0.24 m², P < 0.001), and had a higher STS mortality risk score than men (27.9 ± 17.0 vs. 20.8 ± 16.8 P = 0.01). There was no difference in survival to discharge (P = 0.3). Patients receiving the Impella 2.5 pre‐PCI had significantly lower inpatient mortality than those who received support post‐PCI (P = 0.003). However, the magnitude of the survival benefit was significantly greater in women who received the Impella pre‐PCI as compared to men. Overall, 68.8% of women survived with pre‐PCI Impella 2.5 versus 24.2% post‐PCI (P = 0.005) whereas 54.2% of men survived with pre‐PCI Impella 2.5 versus 40.3% post‐PCI (P = 0.1, p‐interaction = 0.07). No differences in timing to intervention were found between men and women.

Conclusions

Early initiation of hemodynamic support prior to PCI with Impella 2.5, in the setting of AMI complicated by CS, was associated with a greater survival benefit to hospital discharge in women compared to men, despite a higher predicted risk of mortality and a greater revascularization failure rate for women. (J Interven Cardiol 2016;29:248–256)

     

Use of the exercise maximal ST segment/heart rate slope in assessing the results of coronary angioplasty.

A new exercise test was used to assess the effects of coronary angioplasty in 22 patients. Twenty five angioplasty procedures were performed and the exercise maximal ST segment/heart rate slope was measured before and after operation on 23 occasions; in two patients treated for unstable angina the slope was measured only after the two procedures. Successful angioplasty (23 of the 25 procedures) resulted in a significant reduction of the maximal ST/HR slope, usually falling by the equivalent of single vessel disease according to previously published criteria. When angioplasty produced little angiographic change (two of the 25 procedures) the maximal ST/HR slope was not significantly altered. A second, and successful, angioplasty for these two patients led to a significant reduction of the maximal ST/HR slope. Twelve patients were restudied by coronary angiography and exercise testing approximately six months after angioplasty. Of these, six had experienced recurrent chest pain, and the exercise test successfully identified the three who had restenoses and the three who did not. Thus the maximal ST/HR slope was useful as a non-invasive and accurate method for following the progress of individual patients after coronary angioplasty.     

Results of primary angioplasty for acute myocardial infarction in patients with multivessel coronary artery disease

The influence of multivessel coronary artery disease on the outcome of reperfusion therapy for myocardial infarction has not been fully characterized. Direct coronary angioplasty without antecedent thrombolytic therapy was performed during evolving myocardial infarction in 285 patients with multivessel coronary artery disease at 5.2 +/- 4.2 h after the onset of chest pain. Two vessel disease was present in 163 patients (57%) and three vessel disease in 122 (43%). An anterior infarct was present in 123 patients (43%), cardiogenic shock in 33 (12%) and age greater than or equal to 70 years in 59 (21%). Angioplasty of the infarct-related vessel was successful in 256 patients (90%), including 92% with two vessel and 88% with three vessel disease (p = NS). Emergency bypass surgery was needed in six patients (2%). In-hospital death occurred in 33 patients (12%), including 13 with two vessel and 20 with three vessel disease (p less than 0.05). The mortality rate was only 4% in the subgroup of 101 patients who met entry criteria for thrombolytic trials. The in-hospital mortality rate was 45% in patients in shock and 7% in patients not in shock (p less than 0.01). Logistic regression analysis identified shock and age greater than or equal to 70 years as independently associated with in-hospital death. In 135 patients who underwent predischarge left ventriculography, global ejection fraction increased from 50% to 57% (p less than 0.001) and regional wall motion in the infarct zone improved in 59% of patients. Follow-up data were available in 251 patients (99%) at a mean of 35 +/- 19 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radiologic impact on operative access to a retrorectal cyst

Diverse incisions have been used to excise retrorectal lesions. Operative access must be planned with regard to level and type of lesion, and prevention of postoperative complications. In this case, pelvic contrast CT scan conclusively showed communication between the rectum and a retrorectal cyst-hamartoma. A potential rectocutaneous fistula through the previously planned parasacrococcygeal incision was avoided by this preoperative documentation.     

A randomized trial comparing levo-alpha acetylmethadol with methadone maintenance for patients in primary care settings in Australia

Aims The present study aimed to compare the efficacy of levo‐alpha‐acetylmethadol (LAAM) and methadone, as measured by retention in treatment and heroin use, in a randomized trial conducted under naturalistic conditions. Setting This study is the first randomized trial comparing LAAM with methadone in the primary care setting. Participants were recruited through 29 medical practitioners working in specialist and generalist settings in Australia. Participants Existing methadone maintenance patients, aged 18 years and over and able to give informed consent, were randomized to receive either LAAM or methadone. A total of 93 patients participated. Intervention After being trained in the use of LAAM, existing methadone prescribers were then able to determine an individually tailored treatment regimen for each patient. The trial was an open‐label study. Methadone and LAAM dosing was supervised through local community pharmacies. Participation in ancillary services (e.g. counselling) was optional for all patients. The treatment period for the trial was 12 months. Measurements Baseline, 3‐, 6‐ and 12‐month interviews were conducted. Outcome measures were retention in treatment, self‐reported heroin use and serious adverse events. Findings There were no significant differences between LAAM and methadone on retention in treatment, nor heroin use. There was a trend for LAAM patients to have lower heroin use than methadone patients. Of the seven serious adverse events in the LAAM group, three were not drug‐related. There were two dosing errors. Conclusions This study demonstrates (a) the efficacy of LAAM as a treatment for heroin dependence, and (b) the capacity for LAAM to be effectively delivered in primary care settings by trained general practitioners and pharmacists. The next challenge is to resolve outstanding safety concerns with LAAM.     

Upper digestive tract hemorrhage in cirrhotic patients

Sixteen clinical and biological variables were recorded in 116 episodes of upper digestive tract hemorrhage of known cause in cirrhotic patients. One-dimensional analysis reveals a significant correlation between six variables and the rupture of esophagogastric varices, whereas multiple linear regression and partial correlation analysis reduces the significant variables to two: a history of digestive hemorrhage and the nonalcoholic etiology of the cirrhosis. A value of the discriminant function exists for which the specificity and, consequently, the positive predictive value are equal to 100%, but with a sensitivity of 39%. These results mean that, in an explanatory approach, partial correlation analysis seems to constitute an indispensable complement to analysis of clinical and biological variables, since it reduces the chances of unwarranted explanatory interpretation. However, in a pragmatic approach, the recording of 16 variables does not permit a clear discrimination between ruptured varices and nonruptured varices; this suggests that either other factor(s) remain to be discovered or else that those related to ruptured varices and to acute ulcerations are the same.