Remote preconditioning and major clinical complications following adult cardiovascular surgery: systematic review and meta-analysis.

BACKGROUND: A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. METHODS: Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. RESULTS: In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). CONCLUSION: Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice.

ED and quality of life in CABG patients: an intervention study using PRECEDE-PROCEED educational program.

Some reports have examined ED, an important indicator of quality of life (QoL), in cardiac patients. However, the results of these studies have been contradictory. Although some studies report of improvement of ED following coronary artery bypass graft (CABG), others show either no improvement or worsening of the condition. Given such controversy, this study attempted to examine the status of ED following an educational intervention program called PRECEDE-PROCEED model in CABG patients (the PRECEDE acronym stands for predisposing, reinforcing, enabling constructs in educational/environmental diagnosis and evaluation and PROCEED stands for policy, regulatory and organizational constructs in educational and environmental development). This model is a planning model and offers a framework that enables us to recognize useful intervention strategies in achieving desired outcomes. Specifically, it works on two premises. First, it posits that the purpose of a health program is to improve the QoL for individuals. Second, it works on the principle that a diagnosis should begin with the preferred end result and work backward to assess what must be done to bring about that result. As such, the results of our study showed that the implementation of the intervention program following surgery not only significantly decreased ED but enhanced the QoL. Thus, utilization of educational intervention program after CABG operations is recommended.

First-trimester screening for chromosomal abnormalities by integrated application of nuchal translucency, nasal bone, tricuspid regurgitation and ductus venosus flow combined with maternal serum free ß-hCG and PAPP-A: a 5-year prospective study.

OBJECTIVE: To investigate the performance of first-trimester screening for chromosomal abnormalities by integrated application of nuchal translucency thickness (NT), nasal bone (NB), tricuspid regurgitation (TR) and ductus venosus (DV) flow combined with maternal serum free ß-human chorionic gonadotropin (fß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at a one-stop clinic for assessment of risk (OSCAR). METHODS: In total, 13,706 fetuses in 13,437 pregnancies were screened for chromosomal abnormalities during a period of 5 years. Maternal serum biochemical markers and maternal age were evaluated in combination with NT, NT + NB, NT + NB + TR, and NT + NB + TR + DV flow data in 8581, 242, 236 and 4647 fetuses, respectively. RESULTS: In total, 51 chromosomal abnormalities were identified in the study population, including 33 cases of trisomy 21, eight of trisomy 18, six of sex chromosome abnormality, one of triploidy and three of other unbalanced abnormalities. The detection rate and false-positive rate (FPR) for trisomy 21 were 93.8% and 4.84%, respectively, using biochemical markers and NT, and 100% and 3.4%, respectively, using biochemical markers, NT, NB, TR and DV flow. CONCLUSION: While risk assessment using combined biochemical markers and NT measurement has an acceptable screening performance, it can be improved by the integrated evaluation of secondary ultrasound markers of NB, TR and DV flow. This enhanced approach would decrease the FPR from 4.8 % to 3.4 %, leading to a lower number of unnecessary invasive diagnostic tests and subsequent complications, while maintaining the maximum level of detection rate. Pre- and post-test genetic counseling is of paramount importance in either approach.

Cognitive Emotion Regulation in Children with Acute Lymphoblastic Leukemia.

BACKGROUND: Childhood cancer, as one of the life threatening and most serious health problems, considerably influences the cognitive and social functions of children with cancer and their families; however, surprisingly enough, these children are quite compatible with their peers and even function better emotionally compared with normal children. This matter still remains to be a mystery. METHODS: In this study, the ability of ignoring negative stimuli as a technique of emotion regulation was investigated in children with cancer. For this purpose, 78 children (33 girls and 45 boys aged 3 to 12 years) with pediatric acute lymphoblastic leukemia (ALL), and 89 healthy children (52 girls and 37 boys aged3 to 12 years) participated in this study. At the first stage, a number of positive,negative and neutral pictures were displayed to children. At the second stage, they were asked to identify the pictures from among a collection. RESULTS: Data analysis by MANOVA indicated that children with cancer, compared with healthy children, could recognize more positive images than negative ones. Furthermore, it was found that age, sex, duration of hospital stay, duration of disease and financial situation had an effect on the difference between the two groups. CONCLUSION: Positive bias memory can explain low depression and lack of symptoms of post traumatic stress disorder in children with ALL. Attention shifting is multifactorial phenomenon and neurologic factors and family support play important role in this happening.

Use of a quantitative TaqMan-PCR for the fast quantification of mycobacteria in broth culture, eukaryotic cell culture and tissue.

The quantification of slow-growing mycobacteria such as Mycobacterium tuberculosis or M. bovis from in vitro and in vivo samples is complicated by their long generation time, their ability to form aggregates, and their capacity to persist in a state of dormancy. We compared different methods for the establishment of growth curves for broth cultures of M. bovis bacille Calmette-Guérin (BCG). A quantitative TaqMan-PCR yielded results comparable with those obtained by protein quantification and measurement of the ATP content of the cultures. The quantitative TaqMan-PCR furthermore turned out to be particularly suitable for the measurement of multiplication of BCG within eukaryotic cells. Furthermore, it is a fast method allowing an estimation of the mycobacterial load in tissue long before colony counts can be obtained.

Effects of timolol, betaxolol, and levobunolol on human tenon's fibroblasts in tissue culture.

Evidence has been found suggesting that long-term therapy with topical antiglaucoma medications may decrease the success of glaucoma filtering surgery. To investigate this question further, the antiproliferative effects of the preservative benzalkonium chloride and three pure and commercially available beta-adrenergic antagonist preparations (timolol, betaxolol, and levobunolol) were studied on tissue cultures of human Tenon's capsule fibroblasts. Each drug preparation was tested on three different cell lines. Fibroblast growth was measured with tritiated thymidine uptake and hexosaminidase assays. Trypan blue uptake was used to assess cell viability microscopically. The commercially available preparations containing benzalkonium chloride and those of betaxolol and levobunolol without the preservative had similar inhibitory doses for 50% of cells. The timolol preparation without preservative was significantly less toxic than its commercially available one. The three tested beta-adrenergic blockers did not stimulate fibroblast proliferation directly in this in vitro model. Even when the cultures were washed free of the drugs, growth continued to be suppressed, suggesting that the inhibition was not reversible. An increase in fibroblasts and inflammatory cells after long-term antiglaucoma medical therapy thus may be caused not by a direct stimulation of cell proliferation but by chronic inflammation from the irritating effects of antiglaucoma medications and/or their preservatives.

The effects of the fluorinated pyrimidines FUR, FUdR, FUMP, and FdUMP on human Tenon's fibroblasts.

5-Fluorouracil (5-FU) has effectively inhibited fibroblast proliferation to prevent scar formation and bleb failure after glaucoma filtering surgery. To identify more potent but less toxic antiproliferative drugs, the authors studied cell attachment and proliferation of 5-FU metabolites: 5-fluorouridine (FUR), 5-fluorodeoxyuridine (FUdR), 5-fluorouridine-5'-monophosphate (FUMP), and 5-fluorodeoxyuridine-5'-monophosphate (FdUMP) on human Tenon's fibroblasts in vitro.

The effects of 5-fluorouridine, 5-fluorodeoxyuridine, and 5-fluorodeoxyuridine monophosphate on rabbit tenon's capsule fibroblasts in vitro.

Inhibition of rabbit subconjunctival fibroblast attachment and proliferation by 5-fluorouridine (FUR), 5-fluoro-2 deoxyuridine (FUdR), and 5-fluoro-2-deoxyuridine-5-monophosphate (FdUMP), was determined by 3H-adenosine uptake, cell counting, and colorimetric assays for the concentration range of 1000 to 0.0001 micrograms/ml over an 9 day period. The mean 50% inhibitory doses against proliferation were calculated for each assay. Rabbit fibroblast attachment was not inhibited at any drug concentration by either FUR, FUdR, or FdUMP. For rabbit fibroblast proliferation, FUR was found to be 10-100 fold more potent than FUdR and FdUMP. When comparing the human and rabbit cells, the unpaired t-test analysis showed no consistent statistical difference of the ID50s for FUR, FUdR or FdUMP. Rabbit ocular fibroblasts may be useful in modeling the proliferation of human ocular fibroblasts. These in vitro results may be useful for predicting optimal drug dosages for future in vivo testing of these drugs.

Inhibition of rabbit ocular fibroblast proliferation by 5-fluorouracil and cytosine arabinoside.

Inhibition of rabbit subconjunctival fibroblast attachment and proliferation by the antimetabolites 5-fluorouracil (5-FU) and cytosine arabinoside (ara-C) was determined by radionucleotide uptake, cell counting, and colorimetric assays for the concentration range of 1000 to 0.0001 micrograms/ml over an 11-day period. The mean 50% inhibitory doses (ID50s) against proliferation were calculated for each assay. Rabbit fibroblast attachment was not inhibited at any drug concentration by either 5-FU or ara-C. Ara-C was a 10 to 100 times more potent inhibitor of rabbit fibroblast proliferation than 5-FU. The mean ID50s for rabbit subconjunctival fibroblasts were compared with the mean ID50s from a similar series of experiments conducted in our laboratory on human subconjunctival fibroblasts. Unpaired t-test analysis showed a significant difference between the inhibitory effects of 5-FU on rabbit and human fibroblast proliferation. An ID50 against rabbit fibroblasts was detectable after 24 hours of incubation with 5-FU by the 3H-thymidine uptake assay, whereas the ID50 against human fibroblasts was detectable after 48 hours of incubation. Once inhibition of proliferation occurred, however, human fibroblasts were up to six times more sensitive to the antiproliferative effects of 5-FU than rabbit fibroblasts as measured by the 3H-thymidine uptake assay (p = 0.0005). Unpaired t-test analysis showed no statistical difference between the ID50s of ara-C on rabbit and human fibroblasts. Starting on day 3, however, doses greater than 1 micrograms/ml of ara-C were cytotoxic to rabbit fibroblasts but only cytostatic to human fibroblasts as determined by trypan blue uptake assay microscopically. Rabbit ocular fibroblasts may be useful in modelling the proliferation of human ocular fibroblasts in vitro to a limited degree. This tissue culture system may be useful for predicting optimal drug dosages for in vivo rabbit and human glaucoma filtering surgery.

Na(+)-K(+)-ATPase and changes in ATP hydrolysis, monovalent cation affinity, and K+ occlusion in diabetic and galactosemic rats.

This study showed that steady-state kinetics of ATP hydrolysis by Na(+)-K(+)-ATPase are altered in the BB Wistar diabetic rat and experimental galactosemia. Four days after onset, this change was not evident if NaCNBH3 was omitted during enzyme preparations (indicating reversibility). Ninety days after onset, NaCNBH3 reduction was not necessary to see the change in ATP hydrolysis kinetics (indicating nonreversibility). The change in steady-state ATP hydrolysis was similar to that reported earlier for Na(+)-K(+)-ATPase of the lens epithelium and kidney medulla of diabetic individuals and for two in vitro glycosylation models. Our study also showed that the affinities of Na(+)-K(+)-ATPase for K+ are altered, and Na(+)-K(+)-ATPase-dependent K+ occlusion is inhibited in diabetic and galactosemic animals. Because K+ occlusion is required for efficient K+ transport, this finding supports previous in vitro studies that indicated that glycosylation inhibits pump-dependent K+ transport. Furthermore, our study suggested an irreversible impairment of Na(+)-K(+)-ATPase function in the diabetic BB Wistar rat as early as 15 days after onset, even when blood glucose was maintained at 6.7 mM by daily insulin injection.

The effect of 5-fluorouracil and cytarabine on human fibroblasts from Tenon's capsule.

The in vitro cellular inhibitory effects of two pyrimidine antimetabolites, 5-fluorouracil (5-FU) and cytarabine (ara-C), on the attachment and proliferation of human Tenon's capsule fibroblasts after 1, 2, 3, 5, 7, and 10 days of growth were measured with a Coulter counter, a colorimetric method using the endogenous enzyme hexosaminidase, and 3H-thymidine uptake. Neither 5-FU nor ara-C affected cell attachment. The 50% inhibitory dose (ID50) for 5-FU, as measured by the Coulter counter and hexosaminidase assay, was 0.2 and 0.4 micrograms/ml, respectively, at day 5 and decreased to 0.01 and 0.10 micrograms/ml, respectively, on later days. The ID50 for ara-C as measured by the Coulter counter and hexosaminidase assay was 0.01 and 0.1 micrograms/ml at day 3 and remained constant over time. Much lower ID50s were measured by thymidine uptake for both drugs. These findings may indicate that 5-FU has a delayed effect on cellular proliferation due to conversion into more active metabolites. The ara-C has a direct and constant inhibitory effect on cellular proliferation and is ten times more potent than 5-FU as an antiproliferative drug. Thus ara-C may have clinical utility in preventing failure of glaucoma filtering surgery.