Age of first cancer diagnosis and survival in Bloom syndrome

PurposeThis study aimed to describe the spectrum of cancers observed in Bloom Syndrome and the observed survival and age of first cancer diagnosis in Bloom syndrome as these are not well-defined.MethodsData from the Bloom Syndrome Registry (BSR) was used for this study. Cancer history, ages of first cancer diagnosis, and ages of death were compiled from the BSR and analyzed.ResultsAmong the 290 individuals in the BSR, 155 (53%) participants developed 251 malignant neoplasms; 100 (65%) were diagnosed with 1 malignancy, whereas the remaining 55 (35%) developed multiple malignancies. Of the 251 neoplasms, 83 (33%) were hematologic and 168 (67%) were solid tumors. Hematologic malignancies (leukemia and lymphoma) were more common than any of the solid tumors. The most commonly observed solid tumors were colorectal, breast, and oropharyngeal. The cumulative incidence of any malignancy by age 40 was 83%. The median survival for all participants in the BSR was 36.2 years. There were no significant differences in time to first cancer diagnosis or survival by genotype among the study participants.ConclusionWe describe the spectrum of cancers observed in Bloom syndrome and the observed survival and age of first cancer diagnosis in Bloom syndrome. We also highlight the significant differences in survival and age of diagnosis seen among different tumor types and genotypes.     

Working with the history of life: a researcher mishaps?

In this study, characterized as a qualitative one, whose author tells about her experience when accomplishing her Doctorate thesis for the History of life method. She describes the methodological approach, turning explicit the collection and the report analysis technique as well as the incidental difficulties that may turn up during the research completion. She concludes that this method turns the approach among the researcher and the individuals feasible. It points out the need to include the subjective dimension of the care in the assistance rendered to the clientele.     

Efficacy of lincomycin versus penicillin and clarithromycin in patients with acute pharyngitis/tonsillitis caused by group a beta-hemolytic streptococci and a clinical history of recurrence

This open-label, prospective, randomized, comparative, single-masked study was performed at eight centers in the Philippines and Latin America (Chile, Colombia, Peru, Brazil, and Venezuela). The purpose of this study was to assess the efficacy and tolerability of three different antibiotic regimens for the treatment of acute pharyngitis/tonsillitis as a result of group A beta-hemolytic streptococci (GABHS), and to assess the rate of recurrences. Children (aged 3 to 15 years) and adults with a recent history of tonsillitis associated with a positive rapid diagnostic test for group A streptococcus, later confirmed by positive cultures for GABHS, were randomized to one of the following antibiotic regimens (according to patient age) for 10 days: (1) lincomycin hydrochloride capsules or suspension: adults—two 500-mg capsules two times a day (BID) for 10 days; children—60 mg/kg per day divided BID for 10 days (maximum dose, 1000 mg/d); (2) phenoxymethylpenicillin capsules or suspension: adults—one 500-mg capsule three times a day (TID) for 10 days; children—50 mg/kg per day divided TID for 10 days (maximum dose, 1500 mg/d); (3) clarithromycin capsules or suspension: adults—one 250-mg capsule BID for 10 days; children—7.5 mg/kg per day divided BID for 10 days (maximum dose, 500 mg/d). After the initiation of treatment (12 to 14 days) and 3 months after completion, patients were evaluated to assess clinical and microbiologic recurrences. Our results indicate that all drugs had statistically similar clinical and bacteriologic efficacy as well as tolerability for the treatment of acute GABHS pharyngitis/tonsillitis with a clinical history of recurrence.     

Strategies developed by the elderly for controlling arterial hypertension

We objectified to investigate facing strategies elaborated by old-aged people which were attacked by arterial hypertension, being participants of a self-helping group, in a therapeutic accompaniment. The facing mechanisms corresponded to faith in God, family support, occupational activities accomplishment, leisure activities and group participation. Some old-aged people mentioned the family structure as the sustentation pillar for a better therapeutic following, making the elaboration of adaptative answers possible. We concluded that, in spite of all the felt and referred losses, the old-aged people searched to active mechanisms that propitiate adaptative answers to the health-disease situation.     

Autoantibodies in silicosis patients and in silica-exposed individuals

The aim of this study was to evaluate the prevalence of autoantibodies in silica-exposed patients with and without silicosis and without any known rheumatic disease. We studied 61 males exposed to silica for a mean time of 12.2 ± 10.2 years of exposure. A total of 72.1% (44/61) of them presented with pulmonary silicosis. As control group we included 62 healthy males. In all samples we screened for rheumatoid factor (latex agglutination), antinuclear antibodies (indirect immunofluorescence), anti Scl-70 (ELISA) and ANCA (indirect immunofluorescence technique). One patient (1.6%) of the silica group had weakly positive ANA (titer 1:80, centromeric pattern); one (1.6%) had atypical ANCA and seven patients (11.4%) presented positive rheumatoid factor (values range from 8 to 32 UI/ml). One control patient had a positive RF and none of them had positive ANA or ANCA. All patients and controls were negative for anti-Scl-70. The finding of positive RF was higher in the silica-exposed patients (p = 0.032; Fisher). All patients with positive RF had pulmonary silicosis. In the silica-exposed group we could not find a relationship between the presence of RF and age (p = 0.21; Mann–Whitney), smoking habits (p = 0.25; Fisher) but a positive relationship was found with exposure time to silica dust (p = 0.005; Mann–Whitney). We conclude that there was 11.4% prevalence of low titer RF in the silica-exposed patients without known rheumatic disease. RF was more common in patients with longer exposure to silica dust and appeared only in those with silicosis. The presence of ANA, Scl-70 and ANCA was the same as in the control population.     

Serum Cystatin C Is an Early Predictive Biomarker of Acute Kidney Injury after Pediatric Cardiopulmonary Bypass

Background and objectives: Acute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). Serum creatinine (SCr), the current standard, is an inadequate marker for AKI since a delay occurs before SCr rises. Biomarkers that are sensitive and rapidly measurable could allow early intervention and improve patient outcomes. We investigated the value of serum cystatin C as an early biomarker for AKI after pediatric CPB.Design, setting, participants, & measurements: We analyzed data from 374 prospectively enrolled children undergoing CPB. Serum samples were obtained before and at 2, 12, and 24 hours after CPB. Cystatin C was quantified by nephelometry. The primary outcome was AKI, defined as a ≥50% increase in SCr. Secondary outcomes included severity and duration of AKI, hospital length of stay, and mortality. A multivariable stepwise logistic regression analysis was used to assess predictors of AKI.Results: One hundred nineteen patients (32%) developed AKI using SCr criteria. Serum cystatin C concentrations were significantly increased in AKI patients at 12 hours after CPB (P < 0.0001) and remained elevated at 24 hours (P < 0.0001). Maximal sensitivity and specificity for prediction of AKI occurred at a 12-hour cystatin C cut-off of 1.16 mg/L. The 12-hour cystatin C strongly correlated with severity and duration of AKI as well as length of hospital stay. In multivariable analysis, 12-hour cystatin C remained a powerful independent predictor of AKI.Conclusion: Serum cystatin C is an early predictive biomarker for AKI and its clinical outcomes after pediatric CPB.Acute kidney injury (AKI) occurs commonly world-wide, affecting 2% to 5% of hospitalized patients and independently predicting mortality and morbidity (1). Once established, the treatment of AKI is largely supportive, at an annual cost surpassing $10 billion in the US alone (2). The diagnosis currently depends on detection of reduced kidney function by a rise in serum creatinine (SCr) concentration, which is a delayed and unreliable measure in the acute setting (3). Notably, experimental studies have identified interventions that may prevent or treat AKI if instituted early in the disease process, well before the SCr rises (4). The lack of early predictive biomarkers has impaired our ability to translate these promising findings to human AKI.Cardiac surgery with cardiopulmonary bypass (CPB) is the most frequent major surgical procedure performed in hospitals worldwide, with well over a million operations undertaken each year. AKI is a common and serious complication encountered in 30% to 40% of adults and children after CPB (5,6). AKI requiring dialysis occurs in up to 5% of these cases, in whom the mortality rate approaches 80% (6). However, even minor degrees of postoperative AKI as manifest by only a 0.2 to 0.3 mg/dl rise in SCr from baseline and often thought to be clinically unimportant, portend a significant increase in short-term mortality in adults (7). AKI after cardiac surgery is also associated with a number of adverse outcomes, including prolonged intensive care and hospital stays, diminished quality of life, and increased long-term mortality (8). Infants and children with congenital heart disease may be especially vulnerable to developing AKI since many require multiple surgeries for stepwise repair of complex congenital anomalies. These patients represent an ideal group for the validation of AKI biomarkers since confounding co-morbid conditions, such as advanced age, pre-existing renal insufficiency, hypertension, atherosclerotic vascular disease, and diabetes are usually absent.Serum cystatin C has been validated as a marker to estimate GFR in several patient populations, including kidney transplants (9) and critically ill patients (10), and more recently has shown promise as an early biomarker of AKI after adult cardiac surgery (11). Cystatin C is an endogenous cysteine proteinase inhibitor produced by nucleated cells at a constant rate. It is freely filtered at the glomerulus, reabsorbed and catabolized, but is not secreted by the tubules. Importantly, cystatin C is readily measurable using clinical laboratory platforms and does not increase with urinary tract infection or in chronic nonrenal disease, such as malignancy.For this study, we sought to (1) determine the accuracy of early serum cystatin C measurements for the prediction of AKI after pediatric CPB; (2) determine the relationship between cystatin C measurements and renal outcomes (duration and severity of AKI); and (3) determine the relationship between cystatin C measurements and clinical outcomes (mortality and length of hospital stay).     

OrganDots--an organotypic 3D tissue culture platform for drug development

INTRODUCTION: There is an urgent need for preclinical testing systems that more accurately reflect responses in human target organs. The use of ex vivo tissues taken out of the human body and kept alive for sufficient time to perform testing has until recently been limited by tissue availability and by the length of time tissues can be kept alive outside the body, however, recent advances in tissue handling and tissue culture techniques have now made it possible to envisage using such tissues for drug discovery on a scale that is of value for the evaluation of compounds prior to testing in humans. AREAS COVERED: The article presents a method for generating 3D microtissues at the air-liquid interface 'OrganDots' which are formed by reaggregating primary tissues or stem cell-based material which may be useful in drug discovery and development. The article compares this method with other methods for obtaining ex vivo tissues and looks at their uses as surrogates to testing compounds in humans. EXPERT OPINION: Reconstituting tissues in vitro has now reached a point where they can be used to profile the activity of compounds prior to in vivo testing. The ability to reconstitute tissues from primary material and the ability to synthesize new tissues in vitro from stem cells may lead to new testing systems that better reflect human pathophysiology and may allow individual differences to be expressed in vitro. These new drug testing systems should lead to more predictable in vitro drug testing systems in the near future.     

Cognition in novice ecstasy users with minimal exposure to other drugs: a prospective cohort study

CONTEXT: Ecstasy (street name for [+/-]-3,4-methylenedioxymethamphetamine [MDMA]) use has been associated with cognitive deficits, especially in verbal memory. However, owing to the cross-sectional and retrospective nature of currently available studies, questions remain regarding the causal direction and clinical relevance of these findings. OBJECTIVE: To examine the relationship between Ecstasy use and subsequent cognitive performance. DESIGN: A prospective cohort study in Ecstasy-naive subjects with a high risk for future first Ecstasy use, as part of the Netherlands XTC Toxicity study. The initial examination took place between April 10, 2002, and April 28, 2004; follow-up was within 3 years after the initial examination. Setting and PARTICIPANTS: One hundred eighty-eight healthy Ecstasy-naive volunteers (mean age, 22 years) were recruited. Of these, 58 subjects started using Ecstasy (mean cumulative dose, 3.2 tablets; median cumulative dose, 1.5 tablets). They were compared with 60 persistent Ecstasy-naive subjects matched on age, sex, intelligence, and use of substances other than Ecstasy. Differences in cognition between Ecstasy users and Ecstasy-naive subjects were adjusted for differences in cannabis and other recreational drug use. MAIN OUTCOME MEASURES: Change scores between the initial examination and follow-up on neurocognitive tests measuring attention, working memory, verbal and visual memory, and visuospatial ability. RESULTS: At the initial examination, there were no statistically significant differences in any of the neuropsychological test scores between persistent Ecstasy-naive subjects and future Ecstasy users. However, at follow-up, change scores on immediate and delayed verbal recall and verbal recognition were significantly lower in the group of incident Ecstasy users compared with persistent Ecstasy-naive subjects. There were no significant differences on other test scores. CONCLUSIONS: Our findings suggest that even a first low cumulative dose of Ecstasy is associated with decline in verbal memory. Although the performance of the group of incident Ecstasy users is still within the normal range and the immediate clinical relevance of the observed deficits is limited, long-term negative consequences cannot be excluded.