Order form for restricting vancomycin prescribing.
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Anti-Bacterial Agents↗
Biomedical subjects
J Piper
Publications and source records attributed to J Piper.
Bacterial vaginosis and intraamniotic infection.
OBJECTIVE: We sought to determine the predictors of intraamniotic infection with use of the presence or absence of vaginal microbes and clinical variables. STUDY DESIGN: Vaginal fluid was collected and analyzed on 936 of 2711 (35%) consecutive patients who were delivered over a 7-month period. Subjects were followed up prospectively for the development of intraamniotic infection. Intraamniotic infection was defined as an intrapartum fever > 37.8 degrees C plus at least two of the five following variables: maternal or fetal tachycardia, leukocytosis, tender uterus, or foul-smelling amniotic fluid. Bacterial vaginosis score and the presence or absence of aerobic vaginal organisms were independent microbial variables. Demographic, maternal, labor, and delivery characteristics were independent clinical variables. Stepwise logistic regression analysis was used to develop adjusted odds ratios for predicting intraamniotic infection (expressed as odds ratio [95% confidence interval]). Selection bias and microbiologic reliability were measured. RESULTS: A bacterial vaginosis score of 7 to 10 (odds ratio 1.7, [95% confidence interval 1.0 to 3.9]), nulliparity (2.1 [1.3 to 3.4]), each hour of internal fetal electrode (1.2 [1.0-1.3]); and, each vaginal examination (1.7 [1.0-3.9]) were predictors of intraamniotic infection. Selected aerobic vaginal organisms such as group B streptococci or gram-negative rods were not predictive. Reanalysis with a bacterial vaginosis score > or = 4 revealed similar predictors of intraamniotic infection. Bacterial vaginosis had an adjusted odds ratio of 1.85 (1.16 to 2.9). Selected higher risk populations, vaginal examinations > or = 6 (n = 365), or rupture of membranes > or = 7 hours (n = 421) did not change the risk of a bacterial vaginosis score > or = 4 (adjusted odds ratio 1.87 and 1.98, respectively). CONCLUSION: Abnormal vaginal flora combines with clinical variables to increase the risk of intraamniotic infection.
Adult↗
Candida (Torulopsis glabrata) liver abscesses eight years after orthotopic liver transplantation.
The authors report the case of a 48-year-old man in whom candida (Torulopsis glabrata) liver abscesses developed 8 years after liver transplantation. After a week of fever, computed tomography and Doppler ultrasonography showed several fluid-filled loculations in the left lobe of the liver and hepatic arterial stenosis. Aspirates from the abscesses contained T. glabrata organisms. This complication probably developed because hepatic arterial stenosis resulted in bile infarcts (bilomas), which were contaminated via the biliary tract with candida from the biliary-enteric anastomosis. Catheter drainage and administration of amphotericin B for 10 weeks permitted successful retransplantation. T. glabrata liver abscesses, a life threatening complication that can occur long after liver transplantation, can be successfully managed by aggressive medical treatment followed by retransplantation.
Candidiasis↗
Effective use of ribonucleotide reductase inhibitors (Didox and Trimidox) alone or in combination with didanosine (ddI) to suppress disease progression and increase survival in murine acquired immunodeficiency syndrome (MAIDS).
Ribonucleotide reductase inhibitors (RRIs) have been recently shown to inhibit retroviral replication. We examined a new series of RRIs, 3,4-dihydroxybenzohydroxamic acid (Didox) and 3,4,5-trihydroxybenzohydroxamidoxime (Trimidox) for their ability to alter disease progression in murine acquired immunodeficiency syndrome (MAIDS), both alone and in combination with 2',3'-dideoxyinosine (ddI). MAIDS disease was induced by inoculation of female C57BL/6 mice with the LP-BM5 murine leukemia virus (MuLV) and disease progression characterized by extensive peripheral lymphadenopathy and splenomegaly. Efficacy of treatment with these drugs was based upon their ability to influence survival and disease pathophysiology by monitoring the development of splenomegaly. Toxicity was determined by changes in body weight, total peripheral white blood cell count and hematocrit. Didox or trimidox monotherapy was associated with increased survival and decreased disease pathophysiology, with no apparent toxicity. Combined with ddI, their ability to reduce development of viral induced splenomegaly was enhanced compared to trimidox, didox or ddI alone. These results demonstrate RRIs have potent activity in reversing the disease manifestations characteristic of MAIDS. Further studies are warranted to determine human clinical efficacy.
Animals↗
Extrahepatic portal vein stenosis in recipients of living-donor allografts: Doppler sonography.
OBJECTIVE: The aim of this study was to describe the appearances obtained and the pitfalls involved with the use of Doppler sonography for detecting portal vein stenoses after surgery in 198 recipients of pediatric reduced-size transplants. SUBJECTS AND METHODS: We analyzed sonographic and Doppler studies after surgery for 167 children (average, 2.5 years old) who were recipients of 198 left lobe or left lateral segment liver segments (79 living-donor allografts and 119 cadaveric grafts). Sonographic and Doppler studies were performed either on the basis of clinical evidence of portal hypertension or as part of a screening protocol. Demographic and surgical data were compared with the incidence of portal vein structure. We calculated pressure gradients from Doppler jet velocities and compared them with gradients measured manometrically from direct portography in 12 patients. Imaging criteria that indicated portal vein stenoses were (1) a visualized portal vein diameter of 2.5 mm or less, (2) an acceleration of flow at the stricture or a poststenotic jet of portal vein flow revealed by Doppler imaging, or (3) both. Stenoses meeting these criteria were verified by surgical or angiographic identification. RESULTS: Seventeen (22%) portal vein stenoses were detected in recipients of the 79 living-donor liver transplants, whereas three (3%) were detected in recipients of the 119 cadaveric grafts (p < .005). The use of cryopreserved venous extension grafts was the most significant parameter of correlation (p < .025). Doppler sonography predicted the stenoses in all cases, although it overestimated the pressure gradients in all but one of the verified cases. Intrahepatic portal vein flow was frequently normal in the presence of significant extrahepatic portal vein stenosis. CONCLUSION: Diagnosis of portal vein stenosis in recipients of living-donor allografts requires real-time visualization of the entire length of the portal vein, combined with spectral and color Doppler investigations of the portal and splenic veins and a search for collateral vessels. Visualization of each component alone may be insufficient. In our study, when care was taken to follow this procedure, sonography accurately showed all angiographically verified portal vein stenoses, although pressure gradients frequently were inaccurate. A protocol for periodic follow-up with real-time and Doppler sonography is crucial for pediatric patients to permit early identification of portal vein stenoses.
Adolescent↗
Hardware and software requirements for quantitative analysis of comparative genomic hybridization.
Recommendations are made for hardware and software capabilities that will permit a level of performance of comparative genomic hybridization (CGH) analysis on metaphase chromosomes that is comparable to the best current practice. Guidelines for interpreting the results of CGH analysis in terms of chromosomal gains or losses are also presented.
Image Processing, Computer-Assisted↗
Computer image analysis of comparative genomic hybridization.
We describe and evaluate the image-processing and analysis techniques we have developed for the quantitative analysis of comparative genomic hybridization (CGH; Science 258:818, 1992). In a typical CGH application, two genomic DNA samples are simultaneously hybridized to metaphase chromosomes and detected with different fluorochromes. The primary data in CGH are contained in the intensity ratios of the fluorochromes as a function of position on the chromosomes, which reflect variation in DNA copy number ratio between the two DNA samples. Analysis involves chromosome segmentation, intensity normalization, background corrections, and calculation of the fluorescence intensity profiles and the ratio profile along the chromosome's length. Profiles from several copies of the same chromosome in different metaphases are averaged to reduce the noise. Confidence intervals are calculated and displayed for the mean profiles. The techniques were evaluated by examining the variability found in comparisons of two normal genomic DNAs, where the ratio was expected to be constant, and by measuring the ratios obtained for cell lines with cytogenetically documented copy number changes involving several chromosomal segments. The limits of sensitivity of CGH analysis were investigated by simulation. Guidelines for the interpretation of CGH data and indications of areas for future development of the analytical techniques are also presented.
Cell Line↗
Application of automation to the detection of radiation damage using FISH technology.
A whole chromosome painting approach was employed to highlight the damaging effects of low-to-moderate doses of ionizing radiation. A detailed tally of damage involving the painted chromosomes 1 and 2 was compiled from visual analysis and compared with the results of an automatic image processing approach, where the possible outcomes were 'normal', 'abnormal', or 'rejected'. The performance of the automatic approach was tested using a set of 9000 bicolour metaphase images harvested from whole-blood cell culture following irradiation levels of 0.0, 0.5, 1.0 and 2.0 Gy. Every metaphase image in the set was analysed visually. The automatic analysis model was based on two simple image criteria to distinguish normal from abnormal; either an increase in the number of painted objects or a large asymmetry in the area distribution of the expected number of painted objects. A result was obtained without a full karyotype analysis. In practice, automatic analysis produced a set of images for review that were enriched by a factor of 3-4 in true abnormal images. Fast visual review of these images (approximately 200/h) selected the true abnormals. A comparison of the automatic analysis with the visual analysis showed that automated analysis correctly identified 60% of normal cells, 59% of abnormal cells and 73% of rejected cells.
Adult↗
Reduction by prostaglandin E1 or prostaglandin E0 of myocardial infarct size in the rabbit by activation of ATP-sensitive potassium channels.
1. This study examined whether pretreatment of rabbits with infusions of prostaglandin E1 (PGE1) or prostaglandin E0 (PGE0) (which were terminated prior to the onset of ischaemia) reduce myocardial infarct size arising from coronary artery occlusion (60 min) and reperfusion (120 min). In addition, we investigated whether the observed cardioprotective effects of these two prostaglandins were due to the activation of ATP-sensitive potassium (KATP) channels. 2. In the anaesthetized rabbit, infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 2 h of reperfusion was 59 +/- 4% (n = 10). PGE1 or PGE0 treatment (1.0 micrograms kg-1 min-1), administered as 1 h pretreatments (0.05 ml min-1, i.v.), significantly reduced infarct size to 44 +/- 6% (n = 6) or 42 +/- 1% (n = 6), respectively. PGE1 or PGE0 pretreatment resulted in a significant reduction in mean arterial blood pressure, which returned to baseline within 15 min of discontinuation of the infusion (i.e. prior to LAL ligation). 3. The reduction in infarct size afforded by PGE1 was abolished by pretreatment of rabbits with the KATP channel blockers, glibenclamide (60 +/- 4%; n = 8) or 5-hydroxydecanoate (58 +/- 6%; n = 6). Similarly, glibenclamide also largely attenuated the reduction in infarct size afforded by PGE0 (52 +/- 3%; n = 8). 4. We propose that a 1 h pretreatment of PGE1 or PGE0 reduces infarct size by activating protein kinase C resulting in the opening of KATP channels.
Adenosine Triphosphate↗
Endothelin-1-induced reduction of myocardial infarct size by activation of ATP-sensitive potassium channels in a rabbit model of myocardial ischaemia and reperfusion.
1. This study examined whether endothelin-1 (ET-1) reduces infarct size in a rabbit model of acute coronary artery occlusion (60 min) and reperfusion (120 min). In addition, we investigated whether the observed cardioprotective effect of ET-1 was due to the activation of ATP-sensitive potassium (KATP) channels by using two selective antagonists, glibenclamide and sodium 5-hydroxydecanoate (5-HD). 2. In the anaesthetized rabbit, infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 2 h of reperfusion was 55 +/- 4% (n = 11). ET-1 (0.3 nmol kg-1), administered as a bolus injection into the left ventricle, had no effect on infarct size (62 +/- 2%, n = 4). A lower dose of ET-1 (0.03 nmol kg-1) resulted in a significant reduction in infarct size (infarct size 43 +/- 3%; P < 0.05, n = 16). The higher dose (0.3 nmol kg-1), but not the lower dose of ET-1 caused a significant rise in blood pressure, pressure rate index and hence, myocardial oxygen consumption. 3. The reduction in infarct size afforded by ET-1 (0.03 nmol kg-1) was abolished by pretreatment of rabbits with the KATP channel inhibitors, glibenclamide (0.3 mg kg-1) and 5-HD (5 mg kg-1), (infarct size 59 +/- 3 and 63 +/- 4% respectively; n = 4-9). 4. We propose that ET-1 reduces infarct size by opening KATP channels.
Adenosine Triphosphate↗
Rapid on-slide location and analysis of enriched fetal nucleated cells from maternal blood.
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Cell Separation↗
Automatic fluorescence metaphase finder speeds translocation scoring in FISH painted chromosomes.
A fluorescence metaphase finder was constructed with commercially available hardware and a standard Unix workstation. Its accuracy was measured in terms of the number of false positive and false negative detected metaphases on a variety of different slide preparations. The metaphase finder was used in a translocation scoring experiment in which metaphase preparations of human peripheral blood lymphocytes were hybridized with whole chromosome probes to chromosomes #1, #2, and #4. The automatic finder presented metaphases to the cytogeneticist, centered in the eyepieces at x63. The cytogeneticist's scores of analyzable metaphases and of painted chromosomes involved in rearrangements were recorded. The time for the analysis was recorded and compared to the time to analyze a similar number of cells in a purely visual experiment in which the cytogeneticist scanned for cells and analyzed them, both at x63. The results showed that, neglecting the machine time spent scanning unattended, the amount of time required for the analysis was reduced by a factor of three. Furthermore, in this experiment the metaphase finder found more scorable metaphases than the cytogeneticist found by visual scanning. Machine-assisted scoring had additional, less quantifiable, benefits; notably that digital images of metaphases sometimes assisted the analysis of chromosome rearrangements, that cells could be revisited easily, and that the analysis was much less fatiguing.
Cytogenetics↗
Detection and mapping of amplified DNA sequences in breast cancer by comparative genomic hybridization.
Comparative genomic hybridization was applied to 5 breast cancer cell lines and 33 primary tumors to discover and map regions of the genome with increased DNA-sequence copy-number. Two-thirds of primary tumors and almost all cell lines showed increased DNA-sequence copy-number affecting a total of 26 chromosomal subregions. Most of these loci were distinct from those of currently known amplified genes in breast cancer, with sequences originating from 17q22-q24 and 20q13 showing the highest frequency of amplification. The results indicate that these chromosomal regions may contain previously unknown genes whose increased expression contributes to breast cancer progression. Chromosomal regions with increased copy-number often spanned tens of Mb, suggesting involvement of more than one gene in each region.
Breast Neoplasms↗
Automatic scoring of sister chromatid exchanges by image analysis in a dose response experiment.
A system which automatically selects second division metaphases and then, automatically scores the number of SCEs of each cell is described. In an initial set of experiments, the performance of the components of the system was measured using a data set in which metaphases had been visually classified as either 2nd division or other; and in 2nd division metaphases, every SCE had been marked on a hard copy. SCE scoring had a true positive rate of about 75% and a false positive rate of about 1.5 false SCEs per metaphase analyzed. Second division detection had a true positive rate of 80% and a false positive rate of about 10% of the non-2nd division cells. Next, the overall system was compared to human visual scoring in a dose-response experiment by analyzing the effect of mitomycin C on human chromosomes scored visually by two observers and by the fully automatic scoring. Human visual scoring and machine analysis showed similar dose responses, but the variability between them was considerable.
Cell Division↗
Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors.
Comparative genomic hybridization (CGH) is a powerful new method for molecular cytogenetic analysis of cancer. In a single hybridization, CGH provides an overview of DNA sequence copy number changes (losses, deletions, gains, amplifications) in a tumor specimen and maps these changes on normal chromosomes. CGH is based on the in situ hybridization of differentially labeled total genomic tumor DNA and normal reference DNA to normal human metaphase chromosomes. After hybridization and fluorescent staining of the bound DNAs, copy number variations among the different sequences in the tumor DNA are detected by measuring the tumor/normal fluorescence intensity ratio for each locus in the target metaphase chromosomes. CGH is in particular useful for analysis of DNA sequence copy number changes in common solid tumors where high-quality metaphase preparations are often difficult to make, and where complex karyotypes with numerous markers, double minutes, and homogeneously stained chromosomal regions are common. CGH only detects changes that are present in a substantial proportion of tumor cells (i.e., clonal aberrations). It does not reveal translocations, inversions, and other aberrations that do not change copy number. At present, CGH is a research tool that complements previous methods for genetic analysis. CGH will advance our understanding of the genetic progression of cancer and highlight important genomic regions for further study. Direct clinical applications of CGH are possible, but will require further development and validation of the technique. We describe here our recent optimized procedures for CGH, including DNA labeling, hybridization, fluorescence microscopy, digital image analysis, data interpretation, and quality control, emphasizing those steps that are most critical. We will also assess sensitivity and resolution limits of CGH as well as discuss possible future technical improvements.
Chromosome Aberrations↗
Dose dependence of radiation-induced micronuclei in cytokinesis-blocked human lymphocytes.
Following selection of appropriate culture conditions, various experiments were conducted to evaluate the suitability of the micronucleus assay in cytokinesis-blocked lymphocytes for biological dosimetry purposes. A dose-effect relationship was determined, based on the frequency of micronuclei induced by various doses of 60Co gamma-rays. The data were best fitted to a linear-quadratic model. To validate the system, an attempt was made to estimate unknown dose levels from the yield of micronuclei, by inverting the derived dose-response function. It was concluded that the assay provides a valid approach for dose assessment. The size of radiation-induced micronuclei was measured in relation to the dose. A significant difference in the proportion of large micronuclei between high and low doses was observed. The chromosomal composition of micronuclei, detected by immunofluorescent staining of kinetochores, showed that only a small proportion of micronuclei contains kinetochore. The possible contribution of various mechanisms for the formation of large radiation-induced micronuclei is discussed.
Adult↗
Automatic karyotype analysis.
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Centromere↗
Systemic sporotrichosis treated with itraconazole.
Amphotericin B is recommended for the treatment of systemic infection caused by Sporothrix schenckii. However, this agent is toxic, its use is frequently followed by relapse, and some isolates of S. schenckii are resistant. Recent studies suggest that newer azole compounds, such as itraconazole, are effective in cutaneous and lymphocutaneous sporotrichosis, but data on their efficacy in systemic infections are scarce. We used itraconazole in the sequential treatment of six patients with systemic sporotrichosis: three with bone and joint disease and three with disseminated infection manifested by subcutaneous nodules. In all six cases, symptoms and signs of infection improved, with resolution of subcutaneous nodules, normalization of imaging studies, cessation of wound drainage, and return of joint mobility and function. No toxicity was noted. One patient with disseminated infection had a relapse while receiving 100 mg of itraconazole daily. The average duration of follow-up was 18 months. Thus itraconazole appears promising for the treatment of systemic sporotrichosis. A dose of at least 200 mg/d appears to be needed to prevent relapse.
Adult↗