Preoperative preemptive drug administration for acute postoperative pain: A systematic review and meta-analysis.

Preoperative administration of pharmacological substances, such as non-steroidal anti-inflammatory drugs or opioids, has been gaining acclaim as a preemptive measure to minimize postoperative pain. This systematic review and meta-analysis aimed at evaluating the effectiveness of this approach in adults undergoing surgical procedures. MEDLINE, EMBASE and the Cochrane Central Register were searched from inception through January 2015. Data from randomized placebo-controlled trials were screened, extracted and assessed for risk of bias according to The Cochrane Collaboration's Tool by two independent authors. The primary outcome measure was reduction in postoperative analgesic consumption during 24 h post surgery; effects were described as mean differences between the drug and placebo arms with corresponding 95% confidence intervals (CIs) and were pooled using random-effects models. Potential publication bias was tested using funnel plots and Egger's regression test for funnel plot asymmetry. Screened were 511 records, of which 39 were included in the final synthesis with data from 3172 patients. A significant reduction in postoperative analgesic consumption was observed using preoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs; 95% CI, -0.61 to -0.14; 31 comparisons), chiefly by the COX-2 inhibitors class (95% CI, -0.95 to -0.33; 13 comparisons). Significant reduction was also observed for gabapentin (95% CI, -1.60 to -0.38; 6 comparisons). No significant effects were observed using opioids, propionic acids or oxicam derivatives. WHAT DOES THIS REVIEW ADD?: Current analyses endorse the effectiveness of COX-2 inhibitors and gabapentin in reducing acute postoperative pain when administered preemptively presurgery. Such corroboration is not found for opioids and other NSAID classes.

A novel electroencephalography-based tool for objective assessment of network dynamics activated by nociceptive stimuli.

BACKGROUND: Pain perception is typically assessed using subjective measures; an objective measure of the response to pain would be valuable. In this study, Brain Network Activation (BNA), a novel multivariate pattern analysis and scoring algorithm, was applied to event-related potentials (ERPs) elicited by cortical responses to brief heat stimuli. Objectives of this study were to evaluate the utility of BNA as a quantitative and qualitative measure of cortical response to pain. METHODS: Contact Heat Evoked Potentials (CHEPs) data were collected from 17 healthy, right-handed volunteers (10 M, 7F) using 5 different temperatures (35, 41, 46, 49 and 52 °C). A set of spatio-temporal activity patterns common to all the subjects in the group (Reference Brain Network Model; RBNM) was generated using the BNA algorithm, based on evoked responses at 52 °C. RESULTS: Frame by frame 'unfolding' of the brain network across time showed qualitative differences between responses to painful and non-painful stimuli. Brain network activation scores were shown to be a better indicator of the individual's sensitivity to pain when compared to subjective pain ratings. Additionally, BNA scores correlated significantly with temperature, demonstrated good test-retest reliability, as well as a high degree of sensitivity, specificity and accuracy in correctly categorizing subjects who reported stimuli as painful. CONCLUSIONS: These results may provide evidence that the multivariate analysis performed with BNA may be useful as a quantitative, temporally sensitive tool for assessment of pain perception.

Comparison of VivaSight double-lumen tube with a conventional double-lumen tube in adult patients undergoing video-assisted thoracoscopic surgery.

The efficiency of a double-lumen tube depends on its position in the airways, which can be verified by fibreoptic bronchoscopy. The VivaSight DL is a single-use double-lumen tube with a camera embedded in the tube's right side. The view from the camera appears continuously on a monitor. In this prospective study of 71 adult patients, we compared intubation times using either the VivaSight DL or a conventional double-lumen tube. Median (IQR [range]) duration of intubation with visual confirmation of tube position was significantly reduced using the VivaSight DL compared with the conventional double-lumen tube (51 (42-60 [35-118]) s vs 264 (233-325 [160-490]) s, respectively, p < 0.0001). None of the patients allocated to the VivaSight DL required fibreoptic bronchoscopy during intubation or surgery. The VivaSight DL enables significantly more rapid intubation compared with the conventional double-lumen tube.

Differential diagnosis of adnexal masses: sequential use of the risk of malignancy index and HistoScanning, a novel computer-aided diagnostic tool.

OBJECTIVE: To assess the value of ovarian Histo-Scanning(™) , a novel computerized technique for interpreting ultrasound data, in combination with the risk of malignancy index (RMI) in improving triage for women with adnexal masses. METHODS: RMI indices were assessed in 199 women enrolled in a prospective study to investigate the use of HistoScanning. Ultrasound scores were obtained by blinded analysis of archived images. The following sequential test was developed: HistoScanning was modeled as a second-line test for RMI between a lower cut-off and an upper cut-off. The optimal combination of these cut-offs that together maximized the Youden index (Sensitivity + Specificity - 1) was determined. RESULTS: Using RMI at the standard cut-off value of 250 resulted in a sensitivity of 74% and a specificity of 86%. When RMI was combined with HistoScanning, the highest accuracy was achieved by using HistoScanning as a sequential second-line test for patients with RMI values between 105 and 2100. At these cut-off values, sequential use of RMI and HistoScanning resulted in mean sensitivity and specificity estimates of 88% and 95%, respectively. CONCLUSIONS: Our data suggest that HistoScanning may have the potential to improve the diagnostic accuracy of RMI, which could result in better triage for women with adnexal masses. Further prospective validation is warranted.

Optical sectioning by multiexcitonic ladder climbing in colloidal quantum dots.

Optical sectioning is performed by collecting the fluorescent emission of two-exciton states in colloidal quantum dots. The two-exciton state is created by two consecutive resonant absorption events, thus requiring unprecedented low excitation energy and peak powers as low as 10(5) W/cm(2). The depth resolution is shown to be equivalent to that of standard multiphoton microscopy, and it was found to deteriorate only slowly as saturation of the two-exciton state is approached, owing to signal contribution from higher excitonic states.

Do spermatozoa secrete motility enhancing factor?

OBJECTIVES: To determine whether medium conditioned with human spermatozoa was capable of enhancing sperm motility and penetration ability. DESIGN: Paired aliquots of washed spermatozoa were allowed to incubate for nine different incubation periods, ranging from 15 to 240 minutes in 37 degrees C in humidified atmosphere with 5% CO2. After this, they were centrifuged at 600 x g for 6 minutes. The conditioned medium was removed from one tube of each pair and replaced with fresh medium. In the other tube of the same pair the sperm pellet was resuspended in the same medium. In a second set of experiments, conditioned medium was removed from tubes containing samples of spermatozoa after different predefined incubation periods. This was used to replace medium that had been removed from sperm cells that had been incubated for 120 minutes. Motility and penetration of zona-free hamster eggs were assessed. RESULTS: Removal of the incubation medium at times between 15 to 240 minutes resulted in sperm that showed a gradual decrease in motility and penetration ability followed by a gradual increase in motility and penetration ability, i.e., an inverted bell-shaped effect. The addition of conditioned medium obtained after different periods of incubation to spermatozoa where medium was removed after 120 minutes of incubation resulted in an increase in sperm motility and penetration ability. The longer the medium was conditioned with spermatozoa the more prominent the effect on sperm motility and penetration ability, with maximal effect observed with medium conditioned for 120 minutes. CONCLUSIONS: Medium conditioned with human spermatozoa enhances sperm motility and penetration ability.

Ultrasound transmission gel in the vagina can impair sperm motility.

The effect of ultrasound transmission gel on sperm motility was assessed because of a few unsatisfactory post-coital tests, encountered after vaginal ultrasonography in otherwise normal couples. Swim-up samples of spermatozoa from donors and patients with asthenozoospermia were incubated in ultrasonic transmission gel at various concentrations. Sperm progressive motility and viability were checked. Donor sperm progressive motility declined from 90.9 +/- 2.5% (mean +/- SD) to 30.6 +/- 2.7% (P < or = 0.001) within 18 h at a gel concentration of only 10% (by volume). There were no progressive motile spermatozoa after incubation in 80% gel. In the swim-up fraction from asthenozoospermic patients, motility declined from 92.2 +/- 2.5% to 11.6 +/- 2.1% (P < or = 0.001) within 130 min at a gel concentration of 10% (by volume). Eosin staining for viability demonstrated that the loss of motility was mostly due to loss of viability. The use of ultrasound transmission gel should be avoided during follicular follow-up close to the date of expected ovulation in couples who practise dated natural intercourse or cervical insemination. Normal saline is an adequate substitute in this period with relatively large follicles.

Flow cytometric analysis of entire microbial colonies.

Much could be gained if the scope of flow cytometry could be broadened to the study of entire cell colonies, rather than to populations of single, separate cells. This can be achieved by encapsulating single microbial cells in small spheres in a way that allows each cell to multiply and form a colony within its respective microbead, which is then amenable to analysis by flow cytometry. Methods for performing the encapsulation within beads of appropriate size and homogeneity have been developed (Nir et al., Appl. Environ. Microbiol. 56:2870-2875, 1990). We describe here how a variety of properties of the entrapped colonies, such as mass, growth rate, enzymatic activity, and expression of specific antigens, can be measured, and we discuss how these constructs can be utilized to select microbial mutants.

Trophoblasts protect the inner cell mass from macrophage destruction.

Several mechanisms have been suggested to account for the survival of the semiallogeneic fetus in the maternal uterus. However, no data are available to explain how the blastocyst resists the high number of macrophages in the uterus at the time of implantation. The present study examines the in vitro development of murine 3.5-day-old syngeneic or semiallogeneic blastocysts in the presence of nonactivated or lipopolysaccharide (LPS)-activated macrophages. It was found that the in vitro development of blastocysts was undisturbed by the presence of nonactivated or LPS-activated macrophages. The outgrowing trophoblasts were not only nonadhesive to the macrophages but also repelled them actively, thus preventing them from reaching the inner cell mass (ICM). Removing the zona pellucida by use of pronase or killing the ICM by irradiation did not alter the repulsion of macrophages by the trophoblasts. On the other hand, removal of the trophectoderm by antibody and complement treatment rendered the macrophages adhesive and destructive to the ICM. Four of 15 ICM (27%) were destroyed by nonactivated macrophages, and all of the ICM (15/15) were destroyed by LPS-activated macrophages. It is noteworthy that the addition of colchicine, cytochalasin B, proteinase inhibitors, anti-transforming growth factor-beta (TGF beta) antibodies, and indomethacin had no effect on the repulsion of macrophages by the trophoblasts. Therefore, it seems that microtubular proteins, microfilaments, extracellular matrix-degrading enzymes, TGF beta, and prostaglandins are not involved in the repulsion process. These results indicate that trophoblasts protect the ICM from the destructive action of macrophages by a repulsion mechanism of an as yet unknown nature.

Flow cytometry sorting of viable bacteria and yeasts according to beta-galactosidase activity.

We describe a novel method for quantitative measurement of beta-galactosidase (beta-gal) levels in bacteria and yeasts by using flow cytometry, a method which allows viable microbial cells to be sorted on the basis of the expressed activity and to be recultivated. The method is based on encapsulating single cells in agarose microbeads 20 to 30 microns in diameter and analyzing the beta-gal activity of the colonies that develop (containing several hundred cells) by using the fluorogenic substrate fluorescein-di-beta-D-galactopyranoside (FDG). Three strains of Escherichia coli, containing different levels of beta-gal, served as a model system. A high degree of correlation was found between the average fluorescence measured per bead and the level of the enzyme in extracts of the respective strain. Although the use of FDG necessitates cell permeabilization, conditions were found under which a small part of each colony remained viable, yet most of the enzyme was exposed to the substrate. This allowed sorting of microcolonies and plating with close to 100% efficiency. The potential of the technique was demonstrated by selecting beta-gal-positive cells from an artificial mixture of beta-gal-positive and beta-gal-negative E. coli strains.

Single-cell entrapment and microcolony development within uniform microspheres amenable to flow cytometry.

A method is presented for encapsulating single microbial cells in small spheres suitable for analysis and sorting by flow cytometry. The entrapped cells are able to multiply and form colonies contained within their respective microspheres. The system is based on ejecting the cells suspended in a gellable liquid through an orifice vibrating at ultrasonic frequencies, thus shearing the cell-containing jet into uniform droplets. When low-melting-temperature agarose was used, the droplets could be gelled into solid spheres during flight by appropriately directed colling air streams. This gelling was accompanied by significant dehydration, resulting in a twofold decrease in bead diameter and a corresponding increase in agarose concentration. Nevertheless, the microbeads obtained were highly uniform and had diameters which could be precisely controlled in the range of 10 to 40 microns. A variety of bacterial and yeast species were entrapped in agarose beads by using this system. In all cases the cells were able to develop into microcolonies containing as many as several hundred cells. This system enables one to apply the powerful method of flow cytometry to the analysis and sorting of whole microbial colonies. Potential applications of this technology in various areas of microbiology are considered.

Cell-density-dependent lysis and sporulation of Myxococcus xanthus in agarose microbeads.

Vegetative cells of Myxococcus xanthus were immobilized in 25-microns-diameter agarose microbeads and incubated in either growth medium or sporulation buffer. In growth medium, the cells multiplied, glided to the periphery, and then filled the beads. In sporulation buffer, up to 90% of the cells lysed and ca. 50% of the surviving cells formed resistant spores. A strong correlation between sporulation and cell lysis was observed; both phenomena were cell density dependent. Sporulation proficiency was a function of the average number of cells within the bead at the time that sporulation conditions were imposed. A minimum of ca. 4 cells per microbead was necessary for efficient lysis and sporulation to proceed. Increasing this number accelerated the lysis and sporulation process. No lysis occurred when an average of 0.4 cell was entrapped per bead. Entrapping an average of 1.7 cells per bead resulted in 46% lysis and 3% sporulation of survivors, whereas entrapping an average of 4.2 cells per bead yielded 82% lysis and 44% sporulation of the surviving cells. Sporulation and lysis also depended upon the cell density in the culture as a whole. The existence of these two independent cell density parameters (cells per bead and cells per milliliter) suggests that at least two separate cell density signals play a role in controlling sporulation in M. xanthus.

The hormonal response of patients with polycystic ovarian disease to subcutaneous low frequency pulsatile administration of luteinizing hormone-releasing hormone.

Four patients with oligoamenorrhea manifesting hormonal and clinical features of polycystic ovarian disease (PCOD) were selected for treatment. All patients had high luteinizing hormone (LH) levels and a basal LH/follicle-stimulating hormone (FSH) ratio of greater than 3. Three of them had high androgen levels with normal adrenal cortical function. The four patients were treated for 12 cycles by pulsatile LH-releasing hormone (LH-RH) subcutaneously. Frequency of pulses varied between once in every 120 to once in every 400 minutes in consecutive cycles, in an attempt to reverse LH/FSH ratio. The dose of LH-RH varied between 20 and 40 micrograms/pulse. Treatment was monitored hormonally by the determinations of LH, FSH, 17 beta-estradiol, prolactin, progesterone, testosterone (T) (total and free), androstenedione (delta 4A), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) every 2 days. The most striking change was the lowering of the LH/FSH ratio to the normal range, due to LH decrease and FSH increase with a pulse frequency of 180 to 240 minutes. DHEA-S levels reversed to normal in two patients and were reduced in one patient. T and delta 4A levels returned to normal with elevation to normal of SHBG. These hormonal improvements did not result in ovulation as expected (2 of 12 cycles). It may be assumed that either subcutaneous administration is inadequate in PCOD patients or that the frequency of pulses needed to correct the hormonal disturbances in PCOD patients differs from that needed for ovum maturation and ovulation.

Increased placental concentrations of 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in pregnant rats treated with human chorionic gonadotropin.

Pregnant rats were injected intrajugularly with 2500 i.u. human chorionic gonadotropin (HCG) toward the end of gestation (days 18-19) and 7.0 pmoles of tritiated 25-hydroxyvitamin D3 [( 3H]25(OH)D3) the following day. They were sacrificed ten to 24 hours later. [3H]25(OH)D3 and the in vivo produced [3H]24,25-dihydroxyvitamin D3 [( 3H]24,25(OH)2D3) in lipid extracts from maternal serum, kidneys, placenta and fetal tissues were separated by Sephadex LH-20 chromatography, and high performance liquid chromatography (HPLC). HCG treatment of pregnant rats increased significantly 25(OH)D3 levels in the placenta and kidneys and 24,25(OH)2D3 level in the placenta. Fetal metabolites levels were unaffected by HCG treatment. Serum and kidney levels of 25(OH)D3 and 24,25(OH)2D3 in pregnant rats were significantly lower than in non-pregnant rats. Serum and kidney levels of both metabolites in non-pregnant female rats treated with HCG did not differ from the untreated controls. HCG may, therefore, be involved in regulation of fetoplacental vitamin D metabolism.

Vitamin D3 metabolites in rat epididymis: high 24,25-dihydroxy vitamin D3 levels in the cauda region.

Normal male rats received six subcutaneous injections of 8.0 pmoles of tritiated 25-hydroxy vitamin D3 ([3H]25(OH)D3) or one intrajugular injection of 8.0 pmoles of high specific radioactivity [3H]-25(OH)D3. Lipid extracts of several tissues including the reproductive organs were subjected to sephadex LH-20 chromatography to determine the tissue distribution of the injected material and of the in vivo produced dihydroxylated cholecalciferol metabolites. The nature of the putative 25(OH)D3 and the 24,25-dihydroxy vitamin D3 (24,25(OH)2D3) from epididymis tissue was confirmed by high performance liquid chromatography (HPLC). The epididymis levels of 24,25(OH)2D3 were considerably higher in the cauda epididymis compared to kidney and caput epididymis levels. The other metabolites levels in this tissue were similar to those determined in the kidneys. The amounts of the three metabolites found in all other tissues were well below the cauda epididymis or kidney levels. The findings suggest a possible physiological role for 24,25(OH)2D3 in the epididymis, and are also consistent with data of others which indicated a possible action of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) in rat reproductive tissues.