Retinoblastoma and deletion of the long arm of chromosome 13: An underestimated diagnosis?

We report an infant with normal neurological development and phenotype who developed bilateral retinoblastoma (RB). This patient, despite lack of dysmorphic features, demonstrated constitutional abnormality of the long arm of chromosome 13 on standard karyotype. We recommend systematic cytogenetic examinations complemented by fluorescent in situ hybridization as second-line screening in all patients suspected for hereditary RB despite negative RB1 molecular screening and normal phenotype.     

Towards risk stratification in systemic atherosclerosis: value of myocardial function and viability imaging as an adjunct to MR angiography

Objectives

To longitudinally assess the value of cardiac functional and viability imaging as a supplement to MR angiography in patients with atherosclerotic disease.

Methods

Cardiac MRI was performed in 195 consecutive patients with symptomatic peripheral arterial disease. Of these, 186 patients were followed for 22?±?5 months for the presence of cardiac events (cardiac death, acute coronary syndrome and hospitalisation as a result of congestive heart failure).

Results

Myocardial viability imaging showed a high prevalence of known (n?=?31) and occult myocardial infarctions (MI) (n?=?26). Cardiac events occurred more often in patients with reduced ventricular function (ejection fraction (EF) less than 40%, cardiac event in 4/8 patients; EF 40–55%, cardiac event in 10/40 patients; EF greater than 55%, cardiac event in 15/138 patients) as well as in patients with occult MI (8/25 patients) and known MI (11/30 patients). In patients with normal function, the detection of a previous MI was of high relevance to prognosis.

Conclusions

Both reduced EF and the presence of MI influence patients’ prognoses. Performing cardiac MRI in this patient population may influence further patient management including intensified risk factor intervention.     

Polymorphisms in the UBC9 and PIAS3 genes of the SUMO-conjugating system and breast cancer risk

SUMOylation consists in the covalent conjugation of small ubiquitin-related modifiers to target proteins. SUMOylation participates in processes that are tightly linked to tumorigenesis, and genetic variability in the SUMO-conjugating system may influence the development of breast cancer. We recently reported that variation in the UBC9 gene encoding the SUMO-conjugating enzyme may affect the grade of breast tumors. Following comprehensive in silico analyses for detection of putative functional polymorphisms in 14 genes of the SUMO system, we selected one coding SNP in PIAS3 and seven tag SNPs in UBC9 for association analyses. Results were based on 1,021 cases, and 1,015 matched controls from the population-based GENICA study. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by conditional logistic regression. To explore the association with polymorphisms closely linked to the genotyped variants, multiple imputation based on HapMap data was applied. The study revealed associations of four UBC9 polymorphisms with risk of grade 1 tumors. Comparison of genotype and haplotype models indicated that the best representation of risk solely relied on rs7187167 under dominant penetrance. Women carrying the rare allele showed an increased risk of grade 1 tumors compared with common homozygotes (OR 1.87, 95% CI 1.18–2.95). This effect appeared to be stronger in women with a family history of breast or ovarian cancer. Imputation of polymorphisms in a 300-kb region around the genotyped polymorphisms identified no variants with stronger associations. Our findings suggest that genetic variation in UBC9 may affect the risk of grade 1 breast tumors.     

MicroRNAs: Promising chemoresistance biomarkers in gastric cancer with diagnostic and therapeutic potential

Gastric cancer (GC) is the fourth most common cancer worldwide and ranks second in global cancer mortality statistics. Perioperative chemotherapy plays an important role in the management and treatment of advanced stage disease. However, response to chemotherapy varies widely, with some patients presenting no or only minor response to treatment. Hence, chemotherapy resistance is a major clinical problem that impacts on outcome. Unfortunately, to date there are no reliable biomarkers available that predict response to chemotherapy before the start of the treatment, or that allow modification of chemotherapy resistance. MicroRNAs (miRNAs) could provide an answer to this problem. miRNAs are involved in the initiation and progression of a variety of cancer types, and there is evidence that miRNAs impact on resistance towards chemotherapeutic drugs as well. This current review aims to provide an overview about the potential clinical applicability of miRNAs as biomarkers for chemoresistance in GC. The authors focus in this context on the potential of miRNAs to predict sensitivity towards different chemotherapeutics, and on the potential of miRNAs to modulate sensitivity and resistance towards chemotherapy in GC.     

Blood groups,hemoglobin phenotypes and clinical disorders of consanguineous Yansi population

AIM: To study frequency of blood groups, prevalence of sickle-cell anemia trait and glucose-6-phosphate dehydrogenase deficiency (G6PD), among consanguineous Yansi tribe. METHODS: A total of 525 blood samples were collected, of which 256 among the Yansi population, and 269 for the unrelated control group in the Bandundu province of Democratic Republic of Congo. Blood group antigens were determined in the following systems: ABO, Rh, Kell, Duffy, Kidd and MNS. Blood grouping and extended phenotype tests were performed according to standard immunohematological procedures. Spot tests and tandem mass spectrometry were used respectively for the assessment of G6PD and sickle-cell anemia trait. RESULTS: The frequency of ABO phenotypes conformed to the following order O>A>B>AB with notably 62.5%, 23.8%, 12.1% and 1.6% for the Yansi, and 54.6%, 27.5%, 14.1% and 3.7% for the unrelated control group, respectively (P = 0.19). As for the Rh phenotypes, the most frequent were ccD.ee, ccD.Ee, CcD.ee, corresponding to 71.5%, 12.1% and 12.1% for the Yansi, and 70.6%, 15.6% and 8.2%, for the unrelated control group (P = 0.27). The frequency of MN and Ss phenotypes were statistically different between groups (P = 0.0021 and P = 0.0006). G6PD was observed in 11.3% of subjects in the Yansi group, and in 12.4% of controls (P = 0.74). The sickle-cell anemia trait was present in 22.4% of Yansi subjects and 17.8% in the control group (P = 0.24). Miscarriages and deaths in young age were more common among Yansi people. CONCLUSION: This study shows a significant difference in MNS blood group distribution between the Yansi tribe and a control population. The distribution of other blood groups and the prevalence of hemoglobinopathies did not differ in the Yansi tribe.     

Protective immunity against challenge with Leishmania (Leishmania) chagasi in beagle dogs vaccinated with recombinant A2 protein

In this study, we investigated in dogs the immunogenicity and protective immunity against Leishmania (Leishmania) chagasi infection induced by vaccination with a formulation containing the recombinant A2 protein, an amastigote specific antigen, and saponin. Vaccinated animals produced significantly increased levels of total IgG and IgG2, but not IgG1 anti-A2 antibodies, and remained negative in conventional leishmaniasis serodiagnostic methods. Significantly increased IFN-gamma and low IL-10 levels were detected in vaccinated animals before and after challenge, as compared to control animals. Importantly, while the symptoms onset appeared as early as three months after infection in most control dogs, 14 months after challenge, 5 out of 7 vaccinated dogs remained asymptomatic. Therefore, immunization with rA2 antigen was immunogenic and induced partial protection in dogs, and allowed the serological differentiation between vaccinated and infected animals, an important requirement for a canine visceral leishmaniasis (CVL) vaccine.     

Blue light-filter intraocular lenses in vitrectomy combined with cataract surgery: results of a randomized controlled clinical trial

PURPOSE: To evaluate the effect of the blue light-filter intraocular lenses (IOLs) in vitrectomy combined with cataract surgery, focusing on the surgeon's ability to perform specific vitreoretinal procedures and on the patients' outcome. DESIGN: Randomized clinical trial. METHODS: Sixty patients, recruited from our outpatient department, were assigned randomly to receive an ultraviolet-filter IOL (clear IOL group) or a blue light-filter IOL (yellow IOL group) combined with a vitreoretinal procedure. Main outcome measures were intraoperative conditions for the surgeon and the functional outcome. Second outcome measures were complication rates and vitreoretinal diagnoses. RESULTS: The questionnaire responses showed that the blue light-filter IOLs did not represent an impediment to vitreoretinal surgery (P>.05). No intraoperative complications were encountered in either group. Patients in both IOL groups showed comparable functional results with respect to visual acuity, contrast sensitivity, color vision, and glare effect (P>.05). The functional outcome was influenced significantly by the vitreoretinal diagnosis (P<.01). CONCLUSIONS: With the possible advantage of macular protection and no intraoperative or functional disadvantage, the routine use of the blue light-filter IOL in combined surgery can be recommended.