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Biomedical subjects

A Maas

Publications and source records attributed to A Maas.

At least 37 records · Page 2Linked to original sources

Central venous catheter-related bacteraemia in critically ill neonates: risk factors and impact of a prevention programme.

Risk factors for central venous catheter (CVC)-related bacteraemia among infants admitted to a neonatal intensive care unit (NICU) were analysed and the impact of surveillance and continuing education on the incidence of this complication investigated. Among patients admitted to a NICU, CVC-related bacteraemia increased from 1/15 (7%) in 1987 to 11/26 (42%) in 1988 (P = 0.01). Coagulase-negative staphylococci isolated from bacteraemia patients showed clonal diversity by plasmid and chromosomal fingerprinting. A review of CVC care procedures suggested breaches in aseptic techniques. Catheter-care technique was revised to ensure maximal aseptic precautions, including the use of sterile gloves, gown and drapes. The new policy was promoted by a continuing education programme and regular feed-back of CVC-related bacteraemia incidence to NICU staff. In the four-year follow-up period, the attack-rate of CVC-related bacteraemia decreased to 18/156 (12%) patients [relative risk (RR): 0.27, 95% confidence interval (CI); 0.15-0.51; P < 0.001 vs the previous period]. By using the Cox's model proportional hazards, very low birthweight and the period before use of strict aseptic CVC care were found to be predictors of increased risk of catheter-related bacteraemia after adjustment for duration of catheterization. These data provide further evidence that strict aseptic precautions during the maintenance and utilization of CVC can contribute to lower the risk of catheter infection in critically ill neonates. Regular feedback of surveillance data was associated with a progressive decrease in incidence of infection, suggesting that it improved staff compliance with aseptic precautions.

Bacteremia↗

Composition of human thrombus assessed by quantitative colorimetric angioscopic analysis.

BACKGROUND: Angioscopy surpasses other diagnostic tools, such as angiography and intravascular ultrasound, in detecting arterial thrombus. This capability arises in part from the unique ability of angioscopy to assess true color during imaging. In practice, hardware-induced chromatic distortions and the subjectivity of human color perception substantially limit the theoretic potential of angioscopic color. We used a novel application of tristimulus colorimetry to quantify thrombus color to both aid in its detection and assess its composition. METHODS AND RESULTS: A series of human thrombus models were constructed in vitro. Spatial homogeneity was ensured by light and electron microscopy. Quantitative colorimetric angioscopic analysis demonstrated excellent measurement reproducibility (mean difference, 0.07% to 0.17%), unaffected by illuminating light intensity (coefficient of variation, 0.21% to 3.67%). Colorimetric parameters C1 and C2 were strongly correlated (r=.99, P<.0001) with thrombus erythrocyte concentration. Principal components analysis transformed these parameters into a single value, the thrombus erythrocyte index, with little (0.06%) loss of content. Measured and predicted concentrations were similar (mean difference, 0.16 erythrocytes per 1 ng). Randomly ordered images were also subjected to visual analysis by three experienced angioscopists, with suboptimal levels of both intraobserver (mean kappa=0.63) and interobserver (mean kappa=0.48) agreement. In addition, visual ranking resulted in a Kendall rank coefficient of 0.72 to 0.76 versus a perfect 1.00 from quantitative measurement. CONCLUSIONS: Quantitative colorimetric angioscopic analysis provides a new, objective, and reproducible analytic tool for assessing angioscopic images of human thrombus. Even under ideal circumstances, experienced angioscopists do a poor job of assessing color (and therefore composition) of human thrombi. This technique can, for the first time, provide quantitative information of thrombus composition during routine diagnostic imaging.

Angioscopy↗

The X-linked immunodeficiency defect in the mouse is corrected by expression of human Bruton's tyrosine kinase from a yeast artificial chromosome transgene.

Mutations in the gene for Bruton's tyrosine kinase result in the B cell differentiation defects X-linked agammaglobulinemia in man and X-linked immunodeficiency in mice. Here we describe the generation of two yeast artificial chromosome (YAC)-transgenic mouse strains in which high-level expression of human Btk is provided by endogenous regulatory cis-acting elements that are present on a 340-kb transgene, Yc340-hBtk. The expression pattern of the transgenic human Btk was found to parallel that of the endogenous murine gene. When the Yc340-hBtk-transgenic mice were mated onto a Btk-deficient background, the xid B cell defects were fully corrected: conventional and CD5+ B-1 B cells were present in normal numbers, serum IgM and IgG3 levels as well as responses to T cell-independent type II antigens were in the normal ranges. In vivo competition experiments in Btk+/- female mice demonstrated that in the conventional B cell population the Yc340-hBtk transgene could fully compensate the absence of expression of endogenous murine Btk. We conclude that in the YAC-transgenic mice Btk is appropriately expressed in the context of native regulatory sequences.

Agammaglobulinaemia Tyrosine Kinase↗

[Circumscribed apical left ventricular hypertrophy as the cause of a pronounced T-wave negativity].

HISTORY AND CLINICAL FINDINGS: Two patients, one aged 57 the other 44 years, complained of nonspecific symptom-palpitation, left precordial pain and dyspnoea. There were no contributory findings on physical examination in both cases. INVESTIGATIONS: Both patients had hyperlipoproteinaemia, the younger one hyperuricaemia as well. The electrocardiogram showed deeply negative symmetrical T waves in the precordial leads. Transthoracic and transoesophageal echocardiography demonstrated thickening of the apical left ventricular wall. Coronary heart disease was excluded in both patients by coronary angiography. TREATMENT AND COURSE: The findings were fully explained to both patients. As they had only minor symptoms, no specific treatment was given. CONCLUSION: Isolated apical left ventricular hypertrophy should be considered as a possible cause of marked T-wave inversion in the precordial leads; this special form of hypertrophic cardiomyopathy is rarely seen in Europeans. As autosomal dominant inheritance of this condition has been described in two families, other family members should be studied by echocardiography whenever this abnormality is found.

Adult↗

Inactivation of Btk by insertion of lacZ reveals defects in B cell development only past the pre-B cell stage.

Bruton's tyrosine kinase (Btk) is a cytoplasmic protein kinase that is defective in X-linked agammaglobulinaemia in man and in X-linked immunodeficiency in the mouse. There is controversy regarding the stages of B cell development that are dependent on Btk function. To determine the point in B cell differentiation at which defects in Btk become apparent, we generated a mouse model by inactivating the Btk gene through an in-frame insertion of a lacZ reporter by homologous recombination in embryonic stem cells. The phenomenon of X-chromosome inactivation in Btk+/- heterozygous female mice enabled us to evaluate the competition between B cell progenitors expressing wild-type Btk and those expressing the Btk-/lacZ allele in each successive step of development. Although Btk was already expressed in pro-B cells, the first selective disadvantage only became apparent at the transition from small pre-B cells to immature B cells in the bone marrow. A second differentiation arrest was found during the maturation from IgD(low)IgM(high) to IgD(high)IgM(low) stages in the periphery. Our results show that Btk expression is essential at two distinct differentiation steps, both past the pre-B cell stage.

Agammaglobulinaemia Tyrosine Kinase↗

[Tilt-table study in vasovagal syncope. The diagnostic gain from isoprenaline administration].

OBJECTIVE: The cause of syncope remains unclear in half of the cases, even after extensive neurological and cardiological examination. A study was, therefore, undertaken to determine the number of patients with the suspected diagnosis of vasovagal syncope that were confirmed by the tilting table test and how often it required the additional administration of isoprenaline to do so. PATIENTS AND METHODS: A tilting table test was performed on 75 patients (49 men, 26 women; mean age 41 [17-80] years) with syncopes of uncertain cause, previous examinations having failed to discover any neurological or cardiological cause. The test was done with a head-up angle of 60 degrees for 30 min. ECG and arterial blood pressure by indwelling catheter were recorded continuously. If the test was negative, isoprenaline was given intravenously at a rate of 5 micrograms/min during a five-minute period in the horizontal position, followed by 10 minutes at 60 degrees head-up position. RESULTS: Vasovagal syncope or presyncope was induced in 49 of the 75 patients during the tilting table test, a sensitivity of 65%. But 45% of the tests were positive only with the administration of isoprenaline, i.e. an increase in sensitivity to 81.5%. In 96% of the patients with a positive test there was conformity of symptoms between the induced and the spontaneously occurring syncopes. CONCLUSION: The tilting table test is a valuable means of investigating cases of syncope. More than half of the cases of syncope of uncertain cause can be correctly diagnosed classified in this way. The additional use of isoprenaline infusion greatly increases the sensitivity of the method.

Adolescent↗

Evaluation of protein containing quality control materials for blood gas analysis.

Protein containing quality control (QC) material in ampoules for blood gas, pH and electrolyte analysers has been manufactured using buffered protein (Bovine Serum Albumine, BSA) solution with sodium bicarbonate and chloride salts. For comparison a similar QC material but without protein was manufactured. Results obtained with ampouled QC material depend on pre-analytical effects, on matrix effects and on the stability of the material. Pre-analytical variation occurs with closed and/or opened ampoules. The shaking rate of the ampoule must be high (vortexing) and the duration of shaking long enough (15 seconds) to give good reproducibility. Temperature coefficients of protein containing controls are equal to those of protein free controls when incubated at different temperatures. Vigorously shaking of the ampoule gives a protein foam layer resulting in stable values for pH, pCO2 and pO2 during maximally 6 minutes after opening of the ampoule. Concerning matrix effects the CO2 buffer capacity of protein containing QC material is slightly higher compared to that of protein free QC materials as determined by tonometry with CO2/air gas mixtures and measuring pH and plotting log pCO2 vs. pH. The O2 buffer capacity measured as the bias on a properly functioning blood gas analyser is smaller than the bias of protein free QC material. The protein containing quality control is stable for at least 12 months when stored refrigerated at 2-6 degrees C and 28 days at room temperature.

Acid-Base Equilibrium↗

The need for protein containing quality control materials for blood pH and electrolyte analyzers.

In clinical chemistry quality control refers to monitoring of precision and accuracy of the performance of analytical methods. Calibration solutions and (matrixed) control solutions are used in transferring accuracy between definitive method, reference method and field methods. For this purpose aqueous (protein-free), protein-containing and serum-based types of quality control materials having different matrices are available. Here are presented differences in behaviour between aqueous (protein-free) and protein-containing materials. Potentiometry with an electrochemical cell is an often used field method to determine pH and activity of electrolytes with an Ion-Selective Electrode (ISE). Basically, measured e.m.f.'s of calibrators and sample are translated into the activity of the ionic species of the sample by means of the Nernst equation. Besides the standard e.m.f. (E(zero)) of the electrochemical system, the measured e.m.f. includes the ISE-membrane e.m.f. (EISE) and depends on electrolyte type and its concentration and Eij depends on the composition and geometry of the salt bridge. Both EISE and Eij depend on the sample matrix. Protein-containing samples cause a negative bias on the e.m.f. at the liquid junction and a positive bias at the ISE. When EISE and Eij are compared to the mV span of the reference interval, the effects are large for Ca2+, Na+ and Cl-. Exactly the same effects exist for H+, K+, Li+ and Mg2+ but the inaccuracy is less critical for these ions. It may be concluded that only protein containing controls can detect an error that occurs only with measurements on plasma specimens. In practice this means that calibration is checked with protein-free solutions, but that measurements in plasma are best checked with protein-containing solutions.

Acid-Base Equilibrium↗

Molecular characterization of FrpB, the 70-kilodalton iron-regulated outer membrane protein of Neisseria meningitidis.

The structural gene encoding the 70-kDa outer membrane protein FrpB of Neisseria meningitidis was cloned and sequenced. A mutant lacking FrpB was constructed. No difference in iron utilization between the mutant and the parental strain was observed. A minor effect of the mutation on serum resistance was observed. A topology model for FrpB in the outer membrane is proposed.

Amino Acid Sequence↗

Reduction of intratumoral pH by the mitochondrial inhibitor m-iodobenzylguanidine and moderate hyperglycemia.

The interstitial pH of RIF-1 tumors was selectively lowered by i.p. administration of the mitochondrial inhibitor meta-iodobenzylguanidine (MIBG; 40-100 mg/kg), supported by sustained moderate hyperglycemia (plasma glucose concentration, 14 mM) in rats or by a single i.p. bolus injection of glucose (1.5 g/kg) in mice. Responses were evaluated in a multicenter study by pH measurements with semimicroelectrodes and 31P magnetic resonance spectroscopy, by biochemical analysis of tissue and plasma levels of glucose and lactate, and by positron emission tomography analysis of 2-[18F]fluoro-2-deoxy-D-glucose uptake. In both schedules, treatment with MIBG and glucose reduced the mean intratumoral pH as recorded with semimicroelectrodes to 6.2. In the mouse model, treatment with MIBG plus glucose was accompanied by a 2-3-fold stimulation of 2-[18F]fluoro-2-deoxy-D-glucose uptake and a corresponding increase in tumor glucose content. Responses were maximal in male mice with tumors of 0.2-0.8 g. 31P magnetic resonance spectroscopy analysis revealed no changes in intracellular pH or metabolic status, indicating that only extracellular pH was affected. MIBG was synergistic with bolus or continuous glucose administrations by a dual mechanism. The drug reduced by up to 5-fold the amount of glucose required for effective reduction of intratumoral pH and promoted the availability of (extra) glucose to tumor tissue in a stress-related, sympathomimetic response. Moreover, by converting oxic tumor cells into functionally hypoxic cells, combined treatment resulted in a more homogeneous decrease in intratumoral pH which included better perfused peripheral tumor areas. The effects of combined treatment on tumor glucose metabolism could be monitored noninvasively by 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography analysis.

3-Iodobenzylguanidine↗

Type-1 insulin-like growth factor receptor overexpression produces dual effects on myoblast proliferation and differentiation.

Using a retroviral vector, we developed a line of C2 mouse skeletal myoblasts, C2-LISN, which expressed high levels of the human type-1 insulin-like growth factor (IGF) receptor. When switched to low serum medium, C2-LISN myoblasts underwent terminal differentiation extremely rapidly compared to control C2 myoblasts. In high serum conditions which were not permissive for differentiation, C2-LISN myoblasts expressed ten-fold higher levels of the myogenic transcription factor myogenin than did control C2 myoblasts. When cultured in low serum medium with both transforming growth factor-beta (TGF-beta) and high concentrations of IGF-I, C2-LISN myoblasts failed to differentiate and grew to very high saturation densities, forming multilayers. Upon removal of TGF-beta, multilayered C2-LISN myoblasts differentiated within 2 days. These results demonstrate that overexpression of the type-1 IGF receptor can amplify signals which stimulate myogenic differentiation. Overexpressed type-1 IGF receptors can also mediate strong mitogenic signals if differentiation is inhibited by TGF-beta. The C2-LISN myoblast cell line may be a useful model to investigate the intracellular pathways which stimulate myogenic differentiation. Additionally, overexpression of the type-1 IGF receptor could provide a strategy to expand populations of differentiation-competent myoblasts for experimental or clinical applications.

Animals↗

Identification of the iroA gene product of Neisseria meningitidis as a lactoferrin receptor.

The iroA gene product is an iron limitation-inducible outer membrane protein of Neisseria meningitidis. A spontaneous mutant lacking the gene was unable to bind lactoferrin. Furthermore, Escherichia coli strains expressing the IroA protein were capable of binding lactoferrin. Apparently, the IroA protein functions as a lactoferrin receptor.

Bacterial Outer Membrane Proteins↗

Pseudomonas aeruginosa and Enterobacteriaceae bacteremia after biliary endoscopy: an outbreak investigation using DNA macrorestriction analysis.

PURPOSE: An outbreak of gram-negative bacteremia in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) was investigated to determine the sources of infection and to control transmission. PATIENTS, METHODS, AND RESULTS: The incidence of post-ERCP bacteremia increased from 1.6% (60 of 3,696) procedures to 3.6% (53 of 1,454) procedures (relative risk 2.3, p < 0.0001) after endoscopes were processed in a new automated disinfector. Bacteremia involved nine species of Pseudomonas and Enterobacteriaceae, which were also isolated from processed endoscopes. Seven epidemic strains with highly related genomic macrorestriction profiles each infected 2 or more patients, accounting for 29 (55%) episodes of post-ERCP bacteremia. Strains recovered from endoscopes and from the disinfector were associated with 22 (42%) and 5 (9%) bacteremic episodes respectively. Effective endoscope disinfection was achieved by cleansing and disinfection of a blind channel not processed in the disinfector, additional isopropanol-air flush of all channels, and auto-disinfection of the disinfector. In the following period, the incidence of post-ERCP bacteremia returned to the pre-epidemic rate (1.7%, p = 0.0001). CONCLUSION: Bacterial genome fingerprinting by macrorestriction analysis enabled delineation of a multi-strain outbreak of post-ERCP bacteremia. Cross-contamination, and to a lesser extent, common-source contamination, appeared related to inadequate disinfection of endoscopes processed in an automated disinfector.

Bacteremia↗

Coronary vasodilatory action of elgodipine in coronary artery disease.

The effects of intravenous elgodipine, a new second-generation dihydropyridine calcium antagonist, on hemodynamics and coronary artery diameter were investigated in 15 patients undergoing cardiac catheterization for suspected coronary artery disease. Despite a significant decrease in systemic blood pressure, elgodipine infused at a rate of 1.5 micrograms/kg/min over a period of 10 minutes did not affect heart rate and left ventricular end-diastolic pressure. The contractile responses during isovolumic contraction showed a slight but significant increase in maximum velocity (56 +/- 10 to 60 +/- 10 seconds-1; p less than 0.005), whereas the time constant of early relaxation was shortened from 49 +/- 11 to 44 +/- 9 ms (p less than 0.05). Coronary sinus and great cardiac vein flow increased significantly by 15 and 26%, respectively. As mean aortic pressure decreased, a significant decrease in coronary sinus (-27%) and great cardiac vein (-28%) resistance was observed, while the calculated myocardial oxygen consumption remained unchanged. In all, 69 coronary segments (including 13 stenotic segments) were analyzed quantitatively using computer-assisted quantitative coronary angiography. A significant increase in mean coronary artery diameter (2.27 +/- 0.53 to 2.48 +/- 0.53 mm; p less than 0.000001), as well as in obstruction diameter, (1.08 +/- 0.29 to 1.36 +/- 0.32 mm; p less than 0.02), was observed. The results demonstrate that elgodipine, in the route and dose described, induces significant vasodilatation of both coronary resistance and epicardial conductance vessels, without adverse effects on heart rate, myocardial oxygen demand and contractile indexes.

Adult↗

Comparison of lisinopril and nitrendipine on the pulsatility index in mild essential arterial hypertension.

A double-blind, randomized crossover study was performed in 21 patients with essential arterial hypertension. Nitrendipine 20 mg o.d. and lisinopril 20 mg o.d. were given in a randomized order during a period of each 8 weeks. Nitrendipine and lisinopril decreased systolic and mean arterial blood pressure to a similar level without a significant increase in heart rate. The mean diastolic blood pressure was smaller with the lisinopril treatment than with the nitrendipine treatment. The blood pressure decrease was maintained in the sitting and standing position. Furthermore, only nitrendipine decreased the pulsatility index at the tibial posterior arteries, while lisinopril did not influence it significantly. This finding means that mechanisms other than the blood-pressure lowering effect are involved in the decrease of the pulsatility index.

Adult↗

Induction of dorsal and ventral mesoderm by ectopically expressed Xenopus basic fibroblast growth factor.

Peptide growth factors from the fibroblast growth factor (FGF) and transforming growth factor-beta families are likely regulators of mesoderm formation in the early Xenopus embryo. Although basic FGF is found in the Xenopus embryo at the correct time and at sufficient concentrations to suggest that it is the FGF-type inducer, the lack of a secretory signal sequence in the basic FGF peptide has raised questions as to its role in the inductive process. We show here that Xenopus basic FGF can ectopically induce mesoderm when translated from injected synthetic RNA within the cells of a Xenopus embryo. Basic FGF produced in this manner is able to induce the formation of both dorsal and ventral mesoderm with the type of mesoderm formed dependent on the inherent dorsal-ventral polarity of the animal hemisphere. Surprisingly, although Xenopus basic FGF produced from the injected mRNA has a potent mesodermalizing effect on animal hemisphere cells, virtually no phenotypic effect is observed with intact embryos. These results suggest that the role of Xenopus basic FGF is to specify the size of the marginal zone, and synergistically with a dorsally localized prepatterning signal, to initially establish the dorsal-ventral axis of the mesoderm.

Animals↗