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 In addition, trial principal investigators provided unpublished clinical outcome data.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.

Prevalence and factors associated with exclusive breastfeeding at 6 months of life in Tehran: a population-based study.

Exclusive breastfeeding is the best form of nutrition for infants in the first 6 months of life. The aim of this study was to determine the prevalence of exclusive breastfeeding in Tehran, Islamic Republic of Iran in the first 6 months of life, and the factors that influence it. In a population-based, cross-sectional study 538 mothers with children aged 6-24 months completed an interview questionnaire. Only 46.5% of mothers exclusively breastfed their infant in the first 6 months of life. In multivariate analysis formula supplementation in the hospital (OR = 0.41, 95% CI: 0.17-0.95) and mother receiving conflicting infant feeding advice (OR = 0.53, 95% CI: 0.37-0.78) had a negative effect on exclusive breastfeeding. Mother's intention to exclusively breastfeed (OR = 5.85, 95% CI: 2.88-11.9) and infant having first breast contact 6-30 minutes after delivery (OR = 2.35, 95% CI: 1.17-4.72) had positive effects on exclusive breastfeeding.

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.

Saffron (Crocus sativus) ethanolic extract and its constituent, safranal, inhibits morphine-induced place preference in mice.

The effects of saffron ethanolic extract and its constituent, safranal, on the acquisition and expression of morphine-induced place preference (CPP) in male Swiss Webster mice (20-25 g) were investigated in the present study. An unbiased place conditioning method was applied for assessment of morphine reward properties. The saffron extract and safranal were administered intraperitoneally (i.p.) during (acquisition) or after induction (expression) of morphine CPP. In a pilot study, the extract and safranal were alone administered to the animals to assess if they have any reward properties. Subcutaneous (s.c.) of morphine (4 and 8 mg kg(-1)) and extract (50 mg kg(-1); i.p.) induced CPP. Extract (10, 50 and 100 mg kg(-1); i.p.) reduced the acquisition and expression of morphine CPP. The same results were obtained when safranal (1, 5 and 10 mg kg(-1), i.p.) was used. It may be concluded that both ethanolic saffron extract and safranal can inhibit the acquisition and expression of morphine-induced CPP in the mice.

The effects of lamotrigine on the acquisition and expression of morphine-induced place preference in mice.

The purpose of the present study is to determine the effects of the anticonvulsant drug, lamotrigine, on the acquisition and expression of morphine-induced place preference in mice. Lamotrigine prevents the release of glutamate from presynaptic neurons and inhibits action potential in postsynaptic area by inhibiting presynaptic sodium and calcium channels. Because of such properties, lamotrigine is used for reducing craving for and use of cocaine, alcohol and abused inhalant. So, to determine the effects of lamotrigine on opiates; specifically morphine, 180 male Swiss-Webster mice (20-35 g) were used in this study. Conditioned place preference, was assessed using a biased place conditioning paradigm. In a pilot study the effects of various doses of morphine (2.5, 5 and 10 mg kg(-1)), alone, or in combination with lamotrigine (1, 5 and 25 mg kg(-1)) on the place conditioning paradigm were examined. Animals were injected with the aforementioned doses of lamotrigine 60 min either prior to each morphine injections (acquisition) or prior to the start of the expression on the test day (expression). Administration of different doses of morphine (2.5, 5 and 10 mg kg(-1)) induced conditioned place preference whereas the administration of different doses of lamotrigine (1, 5 and 25 mg kg(-1)) failed to induce place preference. Acquisition and expression of morphine-induced CPP were reduced by lamotrigine at doses of 1, 5 and 25 mg kg(-1) and 5 and 25 mg kg(-1), respectively. Physiological mechanisms of action of lamotrigine and its potential therapeutic use in the treatment of drug-dependence are discussed.

[Slow growth rate of mycobacteria. Possible reasons and significance for their pathogenicity]. / Das langsame Wachstum von Mykobakterien. Mögliche Ursachen und Bedeutung für die Pathogenität.

A characteristic feature of mycobacteria is their slow growth rate, which in addition strongly varies in different species of the genus. All highly pathogenic species such as M. tuberculosis and M. leprae causing tuberculosis and leprosy, respectively, belong to the slow growing mycobacteria, while the apathogenic and opportunistic species are members of the fast growing mycobacteria. This suggests that the question be posed whether there is causality between mycobacterial growth rate and virulence. We discuss possible reasons for the slow and variable growth rates of mycobacteria and the current state of knowledge concerning the significance of slow growth for mycobacterial pathogenicity.

Phase-locking in double-point-contact spin-transfer devices.

Spin-transfer in nanometre-scale magnetic devices results from the torque on a ferromagnet owing to its interaction with a spin-polarized current and the electrons' spin angular momentum. Experiments have detected either a reversal or high-frequency (GHz) steady-state precession of the magnetization in giant magnetoresistance spin valves and magnetic tunnel junctions with current densities of more than 10(7) A cm(-2). Spin-transfer devices may enable high-density, low-power magnetic random access memory or direct-current-driven nanometre-sized microwave oscillators. Here we show that the magnetization oscillations induced by spin-transfer in two 80-nm-diameter giant-magnetoresistance point contacts in close proximity to each other can phase-lock into a single resonance over a frequency range from approximately <10 to >24 GHz for contact spacings of less than about approximately 200 nm. The output power from these contact pairs with small spacing is approximately twice the total power from more widely spaced (approximately 400 nm and greater) contact pairs that undergo separate resonances, indicating that the closely spaced pairs are phase-locked with zero phase shift. Phase-locking may enable control of large arrays of coupled spin-transfer devices with increased power output for microwave oscillator applications.

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.

Studies on the size and stability of chlorpromazine hydrochloride nanostructures in aqueous solution.

The mean aggregate number (MAN) of the antipsychotic drug chlorpromazine hydrochloride (CPZ) nanostructure was investigated by fluorescence quenching using 9-methylanthracene (9-MA) as the quencher. The method was designed to take advantage of the intrinsic fluorescent properties of CPZ. The validity of this method was supported by the results obtained for the MAN which was determined to be approximately 37 for a solution of 10 mM CPZ in 0.1 M pH 6.5 phosphate buffer. An increase in the aggregate size with increasing drug concentration confirmed the stepwise aggregation theory of CPZ micelle formation. Differential scanning calorimetry was used to examine the effects of concentration on the thermodynamics of micellization. The enthalpy of demicellization increased with increasing CPZ concentration (5-12 mM), suggesting a greater stability of the aggregates at higher concentrations. At amphiphile concentrations higher than 12 mM, a plateau of approximately 10 kJ/mol was observed as the enthalpy of demicellization. Fluorescence lifetime results revealed a two-component system at low CPZ concentration, while data at amphiphile concentrations higher than 12 mM could not be fitted to either single or multi-component lifetime values, suggesting an increase in dispersity in these nanostructures at higher CPZ concentrations. Temperatures higher than 40 degrees C tend to destabilize the larger micelles, and demicellization was observed after approximately 45 degrees C. Changes in osmotic pressure in the presence of dextrose up to 0.3 M had no significant effect on the size of these micellar nanostructures.

Advances in the stable isotope-mass spectrometric measurement of DNA synthesis and cell proliferation.

Methods for measuring rates of DNA synthesis, and thus cell proliferation, in humans had not been available until recently. We (D. C. Macallan, C. A. Fullerton, R. A. Neese, K. Haddock, S. S. Park, and M. K. Hellerstein, 1998, Proc. Natl. Acad. Sci. USA 95, 708-713) recently developed a stable isotope-mass spectrometric technique for measuring DNA synthesis by labeling the deoxyribose (dR) moiety of purine deoxyribonucleotides through the de novo nucleotide synthesis pathway. The original analytic approach had limitations, however. Here, we describe technical improvements that increase yield, stability, sensitivity, and reproducibility of the method. The purine deoxyribonucleoside, deoxyadenosine (dA), is directly isolated from hydrolysates of DNA by using an LC18 SPE column. Two derivatives were developed for analyzing the dR moiety of dA alone (without the base), an aldonitrile-triacetate derivative, and a reduced pentose-tetraacetate (PTA) derivative. The PTA derivative in particular exhibited greater stability (no degradation after several weeks), greater GC/MS signal, and much less abundance sensitivity of isotope ratios (i.e., less dependence of mass isotopomer abundances on the amount of material injected into the mass spectrometer source), compared to previous derivatives of dA. The need for complex, multidimensional abundance corrected standard curves was thereby avoided. Using the PTA derivative, dR enrichments from DNA of fully turned over cells of rodents with 2H2O enrichments in body water of 2.2-2.8% were 9.0-9.5%, and less than 1.0 microg DNA (ca. 2 x 10(5) cells) was required for reproducible analyses. In summary, these methodologic advances allow measurement of stable isotope incorporation into DNA and calculation of cell proliferation and death rates in vivo in humans and experimental animals, with fewer cells, greater reproducibility, and less labor. Many applications of this approach can be envisioned.

Comparative efficacy of antiviral drugs on human ocular fibroblasts.

The effects of several antiviral drugs on fibroblast attachment and proliferation from human Tenon's capsule were investigated. These drugs included purine nucleoside analogs, vidarabine and acyclovir (ACV); pyrimidine nucleoside analog, AZT; and a synthetic cyclic primary amine, amantadine. Fibroblast attachment and proliferation inhibition were determined by Coulter counter, a colorimetric assay of the enzyme hexosaminidase, and a 3H-thymidine uptake assay. Amantadine and AZT inhibited fibroblast attachment at concentrations higher than 6.61 x 10(-4)M and 3.73 x 10(-4) M, respectively. Amantadine and AZT had inhibitory effects on fibroblast proliferation as early as day 1, whereas vidarabine and ACV manifested their inhibitory effects after day three by Coulter counter and hexosaminidase assays. For amantadine, AZT, ACV and vidarabine, the 50% inhibitory dose (ID50) were 4.94 x 10(-5) M, 1.26 x 10(-5) M, 4.60 x 10(-4) M, and 1.52 x 10(-5) M at day 9, respectively, as measured by 3H-thymidine uptake assay. All four antiviral agents tested had inhibitory effects on human ocular fibroblast proliferation and their inhibitory potential decreased in the order of amantadine > or = vidarabine > AZT > or = ACV.

Frequency-dependent effects of amitriptyline and maprotiline on conduction in the guinea pig His-Purkinje-system in vivo.

In the Cardiac Arrhythmia Suppression Trial antiarrhythmic drug therapy with slow kinetic sodium channel blockers (class Ic antiarrhythmic drugs) was associated with excess mortality, presumably due to drug induced proarrhythmia. It has been suggested that the degree of rate-dependent conduction slowing produced by agents that have sodium channel blocking properties may be related to the proarrhythmic propensity of these agents. In the present study, rate-dependent conduction slowing by the antidepressants amitriptyline and maprotiline was investigated in anesthetized guinea pigs. After electrical ablation of the sinus node the left atrium was stimulated at cycle lengths between 200 ms and 500 ms. His bundle electrograms were registered by means of an epicardial electrode. Drugs were administered by i.v. infusion of 0.2 mg kg-1 min-1 for 30 min followed by 0.1 mg kg-1 min-1 for up to 30 min. Both drugs produced substantial rate-dependent conduction slowing within the His-Purkinje-system. The relationship between pacing rate and conduction slowing was well fitted by linear regression. The steepness of the regression line was significantly greater for amitriptyline than for maprotiline (slope factors: 9.10 x 10(-4) +/- 7.85 x 10(-5), n = 6, vs. 6.29 x 10(-4) +/- 2.97 x 10(-5), n = 6, P < 0.001), indicating that conduction slowing by amitriptyline exhibits a greater degree of rate-dependence than conduction slowing by maprotiline.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Immediate-early gene expression is sufficient for induction of natural killer cell-mediated lysis of herpes simplex virus type 1-infected fibroblasts.

Herpes simplex virus type 1 (HSV-1)-infected human fibroblast (HSV-FS) targets are susceptible to lysis by natural killer (NK) cells, whereas uninfected FS are resistant to lysis. Studies were undertaken to determine the mechanism of this preferential susceptibility. HSV-FS were not intrinsically less stable than FS, as determined by a 51Cr release assay under hypotonic shock in the presence of rat granule cytolysin and by sensitivity to anti-human leukocyte antigen class I antibody plus complement. Single-cell assays in agarose demonstrated that although similar numbers of large granular lymphocytes bound to the HSV-FS and FS targets, the conjugates with HSV-FS were lysed at a much higher frequency than those with FS. These results suggested that both targets are bound by the NK cells but only the HSV-FS were able to trigger lysis. The requirement for active virus expression was demonstrated by failure of emetine-treated HSV-FS targets or targets infected with UV-inactivated HSV to be lysed by NK effectors. To evaluate the role of viral glycoproteins in conferring susceptibility to lysis, Fab were prepared from HSV-1-seropositive sera; these Fab were unable to block lysis of the HSV-FS. Furthermore, incubation in phosphonoacetic acid failed to reduce NK(HSV-FS) activity despite sharp reductions in viral glycoprotein synthesis. Finally, targets infected with tsLB2 at the nonpermissive temperature were lysed as well as or better than targets infected with wild-type virus, indicating that HSV immediate-early gene product expression is sufficient for conferring susceptibility to lysis. We conclude that expression of nonstructural viral proteins or virally induced cellular gene products early in the course of infection rather than structural glycoproteins is required for NK lysis of HSV-FS targets.

Characterization of human and rabbit pigmented and nonpigmented ciliary body epithelium.

Nonpigmented epithelial (NPE) and pigmented epithelial (PE) cells were carefully dissected from both human and rabbit ciliary processes and have been maintained in vitro and partially characterized by morphology and immunocytochemical techniques using polyclonal and monoclonal antibodies against S-100 proteins, collagen type I and type III. The tissue distribution of these proteins was studied in formalin fixed deparaffinized tissue sections of human and rabbit eyes by immunoperoxidase staining techniques. Both NPE and PE cell lines from human and rabbit showed hexagonal morphology by light microscopy; distinct granules containing pigment could be visualized in the PE cell lines, but not in the NPE cells. Antibodies against S-100 proteins stained NPE layer intensely and PE layer slightly in the human tissue sections. The staining was less intense in rabbit tissues than human tissues. The ciliary body stroma was positive for collagen type III and negative for collagen type I or S-100.