Radiation exposure from diagnostic imaging in young patients with testicular cancer.

OBJECTIVES: Risks associated with high cumulative effective dose (CED) from radiation are greater when imaging is performed on younger patients. Testicular cancer affects young patients and has a good prognosis. Regular imaging is standard for follow-up. This study quantifies CED from diagnostic imaging in these patients. METHODS: Radiological imaging of patients aged 18-39 years, diagnosed with testicular cancer between 2001 and 2011 in two tertiary care centres was examined. Age at diagnosis, cancer type, dose-length product (DLP), imaging type, and frequency were recorded. CED was calculated from DLP using conversion factors. Statistical analysis was performed with SPSS. RESULTS: In total, 120 patients with a mean age of 30.7 ± 5.2 years at diagnosis had 1,410 radiological investigations. Median (IQR) surveillance was 4.37 years (2.0-5.5). Median (IQR) CED was 125.1 mSv (81.3-177.5). Computed tomography accounted for 65.3 % of imaging studies and 98.3 % of CED. We found that 77.5 % (93/120) of patients received high CED (>75 mSv). Surveillance time was associated with high CED (OR 2.1, CI 1.5-2.8). CONCLUSIONS: Survivors of testicular cancer frequently receive high CED from diagnostic imaging, mainly CT. Dose management software for accurate real-time monitoring of CED and low-dose CT protocols with maintained image quality should be used by specialist centres for surveillance imaging. KEY POINTS: • CT accounted for 98.3 % of CED in patients with testicular cancer. • Median CED in patients with testicular cancer was 125.1 mSv • High CED (>75 mSv) was observed in 77.5 % (93/120) of patients. • Dose tracking and development of low-dose CT protocols are recommended.

Coronary revascularization and TAVI: before, during, after or never?

Aortic valve stenosis and coronary artery disease (CAD) frequently coexist in elderly patients selected for transcatheter aortic valve implantation (TAVI). Therapeutic strategies to manage concomitant obstructive CAD are therefore an important consideration in the overall management of patients with severe aortic stenosis (AS) undergoing TAVI. Conventional surgical aortic valve replacement and coronary artery bypass grafting is the treatment of choice for low and intermediate risk patients with symptomatic severe AS and concomitant obstructive CAD. However, TAVI and percutaneous coronary intervention (PCI) are viable alternative options for high-risk or inoperable patients presenting with symptomatic severe AS. PCI has been shown to be feasible and safe in selected high-risk or inoperable patients with symptomatic severe AS. However, the optimal timing of PCI relative to the TAVI procedure has been a subject of debate. The most frequent approch is staged PCI typically performed a few weeks prior to TAVI. However, concomitant PCI has also been shown to be a feasible and safe approach, particularly in patients with a low level of CAD complexity and an absence of severe renal impairment. Conversely, staged PCI should be considered in patients with higher degrees of CAD complexity, particularly in the presence of severe renal impairment. The aim of the present review is to discuss the safety and feasibility of performing PCI in elderly patients with severe AS and the optimal timing of PCI relative to the TAVI procedure using the most up-to-date available evidence.

Immobilizing live Escherichia coli for AFM studies of surface dynamics.

Atomic force microscopy (AFM) is a probe-based technique that permits high resolution imaging of live bacterial cells. However, stably immobilizing cells to withstand the probe-based lateral forces remains an obstacle in AFM mediated studies, especially those of live, rod shaped bacteria in nutrient media. Consequently, AFM has been under-utilized in the research of bacterial surface dynamics. The aim of the current study was to immobilize a less adherent Escherichia coli strain in a method that both facilitates AFM imaging in nutrient broth and preserves overall cell viability. Immobilization reagents and buffers were systematically evaluated and the cell membrane integrity was monitored in all sample preparations. As expected, the biocompatible gelatin coated surfaces facilitated stable cell attachment in lower ionic strength buffers, yet poorly immobilized cells in higher ionic strength buffers. In comparison, poly-l-lysine surfaces bound cells in both low and high ionic strength buffers. The benefit of the poly-l-lysine binding capacity was offset by the compromised membrane integrity exhibited by cells on poly-l-lysine surfaces. However, the addition of divalent cations and glucose to the immobilization buffer was found to mitigate this unfavorable effect. Ultimately, immobilization of E. coli cells on poly-l-lysine surfaces in a lower ionic strength buffer supplemented with Mg(2+) and Ca(2+) was determined to provide optimal cell attachment without compromising the overall cell viability. Cells immobilized in this method were stably imaged in media through multiple division cycles. Furthermore, permeability assays indicated that E. coli cells recover from the hypoosmotic stress caused by immobilization in low ionic strength buffers. Taken together, this data suggests that stable immobilization of viable cells on poly-l-lysine surfaces can be accomplished in lower ionic strength buffers that are supplemented with divalent cations for membrane stabilization while minimizing binding interference. The data also indicates that monitoring cell viability as a function of sample preparation is important and should be an integral part of the work flow for determining immobilization parameters. A method for immobilizing a less adherent E. coli mutant for AFM imaging in nutrient broth is presented here in addition to a proposed work flow for developing and optimizing immobilization strategies.

Transcatheter aortic valve implantation: patient selection.

Transcatheter aortic valve implantation (TAVI) is a disruptive technology as it satisfies a previously unmet need which is associated with a profound therapeutic benefit. In randomized clinical trials, TAVI has been shown to improve survival compared with medical treatment among patients considered not suitable candidates for surgical aortic valve replacement (SAVR), and to provide similar outcomes as SAVR in selected high-risk patients. Currently, TAVI is limited to selected elderly patients with symptomatic severe aortic stenosis. As this patient population frequently suffers from comorbid conditions, which may influence outcomes, the selection of patients to undergo TAVI underlies a complex decision process. Several clinical risk score algorithms are routinely used, although they fall short to fully appreciate the true risk among patients currently referred for TAVI. Beyond traditional risk scores, the clinical assessment by an interdisciplinary Heart Team as well as detailed imaging of the aortic valve, aortic root, descending and abdominal aorta as well as peripheral vasculature are important prerequisites to plan a successful procedure. This review will familiarize the reader with the concepts of the interdisciplinary Heart team, risk scores as well as the most important imaging algorithms suited to select appropriate TAVI patients.

Should oral misoprostol be used to prevent postpartum haemorrhage in home-birth settings in low-resource countries? A systematic review of the evidence.

BACKGROUND: Using misoprostol to prevent postpartum haemorrhage (PPH) in home-birth settings remains controversial. OBJECTIVES: To review the safety and effectiveness of oral misoprostol in preventing PPH in home-birth settings. SEARCH STRATEGY: The Cochrane Library, PubMed, and POPLINE were searched for articles published until 31 March 2012. SELECTION CRITERIA: Studies, conducted in low-resource countries, comparing oral misoprostol with a placebo or no treatment in a home-birth setting. Studies of misoprostol administered by other routes were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers and independently checked for accuracy by a third. The quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data were sythesised and meta-analysis was performed where appropriate. MAIN RESULTS: Ten papers describing two randomised and four non randomised trials. Administration of misoprostol was associated with a significant reduction in the incidence of PPH (RR 0.58, 95% CI 0.38-0.87), additional uterotonics (RR 0.34, 95% CI 0.16-0.73), and referral for PPH (RR 0.49, 95% CI 0.37-0.66). None of the studies was large enough to detect a difference in maternal mortality, and none reported neonatal mortality. Shivering and pyrexia were the most common side effects. AUTHOR'S CONCLUSIONS: The finding that the distribution of oral misoprostol through frontline health workers is effective in reducing the incidence of PPH could be a significant step forwards in reducing maternal deaths in low-resource countries. However, given the limited number of high-quality studies in this review, further randomised controlled trials are required to confirm the association, particularly in different implementation settings. Adverse effects have not been systematically captured, and there has been limited consideration of the potential for inappropriate or inadvertent use of misoprostol. Further evidence is needed to inform the development of implementation and safety guidelines on the routine availability of misoprostol.

Comparison of the indentation and elasticity of E. coli and its spheroplasts by AFM.

Atomic force microscopy (AFM) provides a unique opportunity to study live individual bacteria at the nanometer scale. In addition to providing accurate morphological information, AFM can be exploited to investigate membrane protein localization and molecular interactions on the surface of living cells. A prerequisite for these studies is the development of robust procedures for sample preparation. While such procedures are established for intact bacteria, they are only beginning to emerge for bacterial spheroplasts. Spheroplasts are useful research models for studying mechanosensitive ion channels, membrane transport, lipopolysaccharide translocation, solute uptake, and the effects of antimicrobial agents on membranes. Furthermore, given the similarities between spheroplasts and cell wall-deficient (CWD) forms of pathogenic bacteria, spheroplast research could be relevant in biomedical research. In this paper, a new technique for immobilizing spheroplasts on mica pretreated with aminopropyltriethoxysilane (APTES) and glutaraldehyde is described. Using this mounting technique, the indentation and cell elasticity of glutaraldehyde-fixed and untreated spheroplasts of E. coli in liquid were measured. These values are compared to those of intact E. coli. Untreated spheroplasts were found to be much softer than the intact cells and the silicon nitride cantilevers used in this study.

Measuring cell surface elasticity on enteroaggregative Escherichia coli wild type and dispersin mutant by AFM.

Enteroaggregative Escherichia coli (EAEC) is pathogenic and produces severe diarrhea in humans. A mutant of EAEC that does not produce dispersin, a cell surface protein, is not pathogenic. It has been proposed that dispersin imparts a positive charge to the bacterial cell surface allowing the bacteria to colonize on the negatively charged intestinal mucosa. However, physical properties of the bacterial cell surface, such as rigidity, may be influenced by the presence of dispersin and may contribute to pathogenicity. Using the system developed in our laboratory for mounting and imaging bacterial cells by atomic force microscopy (AFM), in liquid, on gelatin coated mica surfaces, studies were initiated to measure cell surface elasticity. This was carried out in both wild type EAEC, that produces dispersin, and the mutant that does not produce dispersin. This was accomplished using AFM force-distance (FD) spectroscopy on the wild type and mutant grown in liquid or on solid medium. Images in liquid and in air of both the wild-type and mutant grown in liquid and on solid media are presented. This work represents an initial step in efforts to understand the pathogenic role of the dispersin protein in the wild-type bacteria.

Haemoglobin A1c (HbA1C) in non-diabetic and diabetic vascular patients. Is HbA1C an independent risk factor and predictor of adverse outcome?

BACKGROUND: Plasma Haemoglobin A1c (HbA1c) reflects ambient mean glycaemia over a 2-3 months period. Reports indicate that patients, with and without diabetes, with an elevated HbA1c have an increased risk of adverse outcome following surgical intervention. Our aim was to determine whether elevated plasma HbA1c level was associated with increased postoperative morbidity and mortality in patients undergoing vascular surgical procedures. METHODS: Plasma HbA1c was measured prospectively in 165 consecutive patients undergoing emergency and elective vascular surgical procedures over a 6-month period. Patients were categorized into four groups depending on whether their plasma HbA1c was < or =6%, 6.1-7%, 7.1-8% or >8% and clinical data was entered into a prospectively maintained database. Patients were also classified by diabetic status with suboptimal HbA1c in a patient without diabetes being >6 to < or =7% and suboptimal HbA1c in a patient with diabetes being >7%. Patients with plasma HbA1c >7% were reclassified as having undiagnosed diabetes mellitus. Composite primary endpoints were all cause 30-day morbidity and mortality and all cause 6-month mortality. Composite secondary endpoints were procedure specific complications, adverse cardiac events, stroke, infection and mean length of hospital stay. RESULTS: Of the 165 patients studied, 43 (26.1%) had diabetes and the remaining 122 (73.9%) did not. The mean age was 72 years and 59% were male. Suboptimal HbA1c levels were found in 58% patients without diabetes and in 51% patients with diabetes. In patients without diabetes those with suboptimal HbA1c levels (6-7%) had a significantly higher incidence of overall 30-day morbidity compared to patients with HbA1c levels < or =6% (56.5 vs 15.7%, p<0.001). Similarly, for patients with diabetes those with suboptimal HbA1c levels (HbA1c >7%) had a significantly higher incidence of 30-day morbidity compared to those with HbA1c levels < or =7% (59.1% vs 19%, p=0.018). Multivariate analysis revealed that a plasma HbA1c level of >6 to < or =7% was a significant independent predictor of overall 30-day morbidity in patients without diabetes undergoing vascular surgical procedures. No difference in mortality, composite secondary endpoints, procedure specific complications, stroke or mean length of hospital stay was observed between any of the groups in the study. CONCLUSION: Suboptimal HbA1c levels may hold prognostic significance in patients without diabetes undergoing vascular surgery.

Effect of endothelial cell-based iNOS gene transfer on cavernosal eNOS expression and mouse erectile responses.

Inducible nitric oxide synthase (iNOS) gene transfer is reported to augment erectile responses in rats, although it is also shown to impair vasorelaxation in cerebral arteries. We investigated the effect of endothelial cell-based iNOS gene transfer on endothelial NOS (eNOS) expression and mouse erectile responses. Human coronary artery endothelial cells (EC) transduced with empty vector (control) or iNOS were grown in culture and transplanted into the corpus cavernosum of severe combined immunodeficient mice. Endothelial NOS expression was compared in control and iNOS-transduced cells grown in the presence or absence of a selective iNOS inhibitor, L-N6- (1-iminoethyl) lysine hydrochloride (L-NIL). At 3-5 days after cell transplantation, we recorded intracorporal pressure (ICP) responses to cavernosal nerve stimulation and measured cavernosal total NO and eNOS protein expression. In this study, EC transduced with iNOS produced significantly more NO than controls but exhibited a twofold downregulation of eNOS protein and mRNA. This effect was reversed by L-NIL. In vivo, the cell-based gene transfer of iNOS led to significantly increased ICP responses, compared to mice transplanted with control ECs. Consistent with the in vitro data, cavernosal lysates had significantly reduced eNOS expression. In conclusion, EC gene transfer of iNOS downregulates EC expression of eNOS by an NOS-dependent mechanism. In the cavernosum of mice transplanted with Inos-transduced EC, nerve-stimulated erectile responses were augmented by the short-term gene transfer. However, our findings suggest that iNOS gene transfer may have deleterious effects on endothelial function if used as a treatment for erectile dysfunction.

Mounting of Escherichia coli spheroplasts for AFM imaging.

The cytoplasmic membrane of Escherichia coli (E. coli) is the location of numerous, chemically specific transporters and recognition elements. Investigation of this membrane in vivo by atomic force microscopy (AFM) requires removal of the cell wall and stable immobilization of the spheroplast. AFM images demonstrate that spheroplasts can be secured with warm gelatin applied to the mica substrate just before the addition of a spheroplast suspension. The resulting preparation can be repeatedly imaged by AFM over the course of several hours. Confocal fluorescence imaging confirms the association of the spheroplasts with the gelatin layer. Gelatin molecules are known to reorder into a network after heating. Entrapment within this gelatin network is believed to be responsible for the immobilization of spheroplasts on mica.

AFM imaging of bacteria in liquid media immobilized on gelatin coated mica surfaces.

Immobilization of particulates, especially biomolecules and cells, onto surfaces is critical for imaging with the atomic force microscope (AFM). In this paper, gelatin coated mica surfaces are shown to be suitable for immobilizing and imaging both gram positive, Staphylococcus aureus, and gram negative, Escherichia coli, bacteria in both air and liquid environments. Gelatin coated surfaces are shown to be superior to poly-L-lysine coated surfaces that are commonly used for the immobilization of cells. This cell immobilization technique is being developed primarily for live cell imaging of Rhodopseudomonas palustris. The genome of R. palustris has been sequenced and the organism is the target of intensive studies aimed at understanding genome function. Images of R. palustris grown both aerobically and anaerobically in liquid media are presented. Images in liquid media show the bacteria is rod shaped and smooth while images in air show marked irregularity and folding of the surface. Significant differences in the vertical dimension are also apparent with the height of the bacteria in liquid being substantially greater than images taken in air. In air immobilized bacterial flagella are clearly seen while in liquid this structure is not visible. Additionally, significant morphological differences are observed that depend on the method of bacterial growth.

Influence of angiotensin II on transmission in the superior cervical ganglion.

The influence of angiotensin II (ANG II) on sympathetic ganglionic transmission was examined in the in situ, normally perfused, superior cervical ganglion in pentobarbitone-anaesthetized rabbits. Compound action potentials were evoked in the external carotid nerve by repetitive electrical stimulation of the decentralized preganglionic cervical sympathetic nerve (supramaximal intensity, 1 ms, 0.5 Hz). A continuous partial nicotinic block was maintained by intravenous infusion of hexamethonium. The converting enzyme inhibitor captopril was infused to prevent the endogenous generation of ANG II. Graduated intravenous infusion of ANG II brought about graduated increases in the height of the S2 potential; the threshold rate of infusion for this effect was 40 ng min-1. At this infusion rate, the plasma concentration of ANG II was estimated to lie between 80 and 600 pg ml-1. While ANG II can modify sympathetic ganglionic transmission, it is unlikely that it has any effect at physiological plasma concentrations of circulating ANG II reported for the rabbit (2-80 pg ml-1).

Respiratory syncytial virus infection in immunocompromised adults.

Respiratory syncytial virus disease was documented in 11 immunocompromised adults, aged 21 to 50. Underlying conditions included bone marrow transplant (6 patients), renal transplant (3 patients), renal and pancreas transplants (1 patient), and T-cell lymphoma (1 patient). Diagnosis of infection was based on specimens from bronchoalveolar lavage, sputum, throat, sinus aspirate, and lung biopsy. The virus was detected simultaneously by antibody in either an immunofluorescence or enzyme-linked immunosorbent assay in 3 of 4 patients whose culture results were positive for respiratory syncytial virus. The virus was an unexpected finding, despite widespread infection in the community. Clinical symptoms included low-grade fever, nonproductive cough, rhinorrhea or nasal congestion, and radiographic evidence of interstitial infiltrates and sinusitis. Aerosolized ribavirin therapy was used in the 6 recipients of bone marrow transplants, 3 of whom required assisted ventilation but died. Death caused by virus infection was documented in 4 of 11 patients. Respiratory syncytial virus disease must be considered in the differential diagnosis of fever and pulmonary infiltrates in immunocompromised adults.

Congenital commissural and lower lip pits in the same patient: report of a case.

A case of simultaneous congenital lip and commissural pits is described. To the authors' knowledge, such an occurrence has not been previously reported to exist in the same patient. The need for genetic counseling in patients with lip pits and the surgical treatment of this deformity is discussed.

Diagnosis of viral pneumonia.

The diagnosis of viral pneumonia has changed during the past decade from a purely clinical diagnosis to one that is both clinical and laboratory in nature. Viral pneumonias can be divided into two clinical groups: the so-called "atypical" pneumonias in otherwise normal hosts, and viral pneumonitis in the immunocompromised host. Clinical factors such as patient age, immune status, time of year, illness in other family members, community outbreaks, onset, severity, duration of symptoms, and the presence of a rash remain important aids in diagnosing viral causes of both atypical pneumonia and pneumonia in the immunocompromised patient. However, advances in virus culture methodologies and the use of monoclonal antibodies coupled with immunofluorescence and ELISA techniques have markedly enhanced both the sensitivity, specificity, and rapidity of the diagnosis of viral pneumonias. Further advances are expected in the future as nucleic acid hybridization techniques are increasingly applied to both viral cultures and direct analysis of clinical specimens.

Rounded atelectasis: a new criterion for benignancy.

A malignancy must be considered whenever a mass lesion is encountered on a chest roentgenogram. Unless an unequivocal diagnosis of a benign lesion is made, thoracotomy is usually indicated. Rounded atelectasis, while only having been recently described, is being encountered with increasing frequency. As illustrated by our three cases, radiologic diagnosis of this entity is a major criterion for judging the benignity of a mass and obviates the need for a thoracotomy.