Bladder cancer biomarkers and their role in surveillance and screening

Early detection of bladder cancer and its recurrences is essential for improved prognosis and long-term survival. The detection and follow-up of these patients is currently based on cystoscopy, which is expensive and invasive, and, in most cases, cytology, which is non-invasive but not very sensitive. During recent years, many urine-based tests have been developed and tested in different patient populations. In this review we discuss new developments for biomarkers in bladder cancer that have potential use in surveillance and screening. In almost all publications authors compare sensitivity of the test with a concomitantly executed cystoscopy, for example, determine cross-sectional sensitivity. However, it has also been shown that false positive test results may be followed by a positive cystoscopy in the near future, showing that cystoscopy itself does not provide 100% sensitivity. This suggests that for a proper evaluation of urine-based tests, longitudinal studies should be carried out and the results communicated to the urologist.     

<Emphasis Type=Italic>CYP2C19</Emphasis> and <Emphasis Type=Italic>ABCB1</Emphasis>gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

Background  

Recent studies have reported the clinical importance of CYP2C19 and ABCB1 polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of CYP2C19 and ABCB1 polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population.     

Assessment of right ventricular systolic function using tricuspid annular-plane systolic excursion in Nigerians with systemic hypertension

Aim

Right ventricular (RV) systolic function in patients with hypertensive heart disease (HHD) is not well characterised. The primary aim of this study was to assess the systolic function of the right ventricle in patients with HHD using tricuspid annular-plane systolic excursion (TAPSE).

Methods

The study was cross-sectional in design and carried out in Kano, Nigeria. Patients were recruited if they had HHD on echocardiography and were at least 15 years of age. Patients with other cardiac pathologies such as ischaemic and valvular heart diseases were excluded. Patients were considered to have abnormal RV systolic function if they had reduced values of TAPSE (< 15 mm). A p-value of < 0.05 was considered statistically significant.

Results

A total of 186 patients were serially recruited over seven months. Of these, 131 (70.4%) had normal RV systolic function (group 1) and 55 patients (29.6%) had abnormal function (group 2). Group 2 patients were older (p = 0.002) and had a higher prevalence of peripheral oedema (p = 0.002), moderate to severe dyspnoea, higher heart rate and lower left ventricular ejection fraction (p < 0.001). Atrial arrhythmias were also more prevalent among group 2 patients (p < 0.05). The best correlate to TAPSE was the septal mitral annularplane systolic excursion (r = +0.541, p < 0.001). Several variables such as age predicted the presence of reduced TAPSE.

Conclusion

The study found that almost one-third of patients with HHD in Kano had RV systolic dysfunction as defined by reduced TAPSE, and these patients had a greater prevalence of factors associated with morbidity and mortality.     

COBALAMIN DEFICIENCY and SMALL BOWEL BACTERIAL OVERGROWTH: A COMMON ASSOCIATION

Background  Bacterial overgrowth may cause cobalamin deficiency through competition for dietary cobalamin in the small intestine. The objective of this study was to prospectively determine the prevalence of small bowel bacterial overgrowth in patients with documented cobalamin deficiency in a tertiary referral centre.
Methods  Patients identified with cobalamin deficiency underwent diagnostic investigations including: Endoscopy (with gastric antrum, gastric body and duodenal biopsies and duodenal aspirate), ¹⁴C-D-Xylose breath test, intrinsic factor antibody, anti-endomysial antibody and red cell folate level. 'Definite' small bowel bacterial overgrowth was defined as either a positive ¹⁴C-D-Xylose breath test or > 100 000 CFU/mL of culture of duodenal aspirate. 'Suspected' small bowel bacterial overgrowth was defined as an elevated red cell folate in the absence of supplemental folate therapy.
Results  Over a 2-year period, 62 patients with cobalamin deficiency were identified, of whom, 26 (42%) had 'definite' small bowel bacterial overgrowth, whilst a further nine (15%) had 'suspected' small bowel bacterial overgrowth. Nineteen (31%) had pernicious anaemia, and no cause for cobalamin deficiency could be found in eight (13%) patients. The diagnosis found in the remaining patients included coeliac disease (4), Crohn's Disease (1), gastric resection (2), vegan (2), homozygotes of the MTHFR gene (C677T) mutation (2), and one had enteropathy associated with common variable immunodeficiency (CVID). 'Definite' small bowel bacterial overgrowth was found to coexist with nine of the 19 cases of pernicious anaemia, two coeliac subjects, one CVID enteropathy and one patient with the MTHFR gene mutation.
Conclusion  Small bowel bacterial overgrowth is commonly associated with cobalamin deficiency.     

QT correction methods in children and adolescents

INTRODUCTION: Accurate determination of the QTc interval has become increasingly important in the assessment of a drug's ability to prolong cardiac repolarization. Previous work suggests the most appropriate correction formula for adults is QTc=QT/RR0.40, but little on correction methods for children and adolescents has been published. METHODS AND RESULTS: In this study, ECG data were obtained from a meta-analysis of seven clinical trials for attention deficit/hyperactivity disorder (ADHD) involving 2,288 children and adolescents. The most appropriate formula for children and adolescents included in this database was found to be QTc=QT/RR0.38. Adjustments of the correction factor specifically for males and females of different ages also are reported. CONCLUSION: QT correction methods developed for adults do not apply to children. As accurate QTc determination plays a larger role in assessing a drug's potential to retard repolarization, use of age- and gender-specific correction formulas becomes more important.     

Current structures of cardiac centers

The "Working Group for Congenital Heart Surgery and Pediatric Heart Surgery" of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) has analysed and recommended structures for congenital heart surgery departments in Germany. The document was worked out according to a similar paper approved earlier by the European Association for Cardio-thoracic Surgery (EACTS). The "Working Group" unifies the majority of cardiac surgeons involved in congenital heart surgery in Germany. Current structures of cardiac centers vary. Therefore the aim of this document is to elucidate additional structural needs for both highly specialized institutions and those for standard care. Specialized centers should allow for treatment of newborns and adult patients with congenital heart disease, include implementation of assist devices and transplantation, possess research facilities and ensure highest standards of education and training. Standard care units do not necessarily need to cater for the above mentioned spectrum. However, the evaluation of quality of care should be given priority in all centers involved in care of patients with congenital heart disease. Data acquisition and transfer must be guaranteed to both the GSTCVS and EACTS in order to ensure national and international comparison of surgical results. This may also give further guidance for improved patient care.     

Stimulation of collagenase 3 expression in synovial fibroblasts of patients with rheumatoid arthritis by contact with a three-dimensional collagen matrix or with normal cartilage when coimplanted in NOD/SCID mice

OBJECTIVE: To study the expression of collagenase 3 (matrix metalloproteinase 13 [MMP-13]) and collagenase 1 (MMP-1) in synovial fibroblasts from patients with rheumatoid arthritis (RA) when cultured within 3-dimensional collagen gels or coimplanted with normal cartilage in immunodeficient NOD/SCID mice. METHODS: Messenger RNA (mRNA) and protein expression of collagenase 3 and collagenase 1 were characterized in synovial and skin fibroblasts by Northern blot and Western blot analysis. The mRNA expression of both collagenases in cell-cartilage implants in NOD/SCID mice was investigated by in situ hybridization in combination with immunohistochemistry of human fibroblasts. RESULTS: Synovial fibroblasts coimplanted with normal cartilage in NOD/SCID mice deeply invaded adjacent cartilage tissue. In this in vivo system of cartilage destruction, collagenase 3 mRNA was induced in synovial fibroblasts at sites of cartilage erosion, while the expression of collagenase 1 mRNA could not be detected. Culture of synovial fibroblasts within 3-dimensional collagen gels was associated with a marked increase in collagenase 3 mRNA expression and proenzyme production. This stimulatory effect was 1 order of magnitude higher in comparison with a 2-4-fold increase upon treatment with interleukin-1beta or tumor necrosis factor a. In contrast, mRNA expression and proenzyme production of collagenase 1 were increased strongly, and to a similar extent, either by contact with 3-dimensional collagen or by proinflammatory cytokines. CONCLUSION: The expression of collagenase 3, in contrast to that of collagenase 1, is preferentially stimulated in synovial fibroblasts by 3-dimensional collagen rather than by proinflammatory cytokines. The induction of collagenase 3 by cell-matrix interactions represents a potential mechanism contributing to the invasive phenotype of synovial fibroblasts at sites of synovial invasion into cartilage in RA.