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Biomedical subjects

K Weiss

Publications and source records attributed to K Weiss.

At least 19 recordsLinked to original sources

A nosocomial outbreak of fluoroquinolone-resistant Streptococcus pneumoniae.

Over the course of a 20-month period, in a hospital respiratory ward in which ciprofloxacin was often used as empirical antimicrobial therapy for lower respiratory tract infections (LRTIs), 16 patients with chronic bronchitis developed nosocomial LRTIs caused by penicillin- and ciprofloxacin-resistant Streptococcus pneumoniae (serotype 23 F). The minimum inhibitory concentration (MIC) of ciprofloxacin for all isolates from the first 9 patients was 4 microg/mL, in association with a parC mutation. Isolates from the subsequent 7 patients all had a ciprofloxacin MIC of 16 microg/mL, in association with an additional mutation in gyrA. The MICs for this isolate were 8 microg/mL of levofloxacin (resistant), 2 microg/mL of moxifloxacin and gatifloxacin (intermediately resistant), and 0.12 microg/mL of gemifloxacin. This outbreak demonstrates the ability of S. pneumoniae to acquire multiple mutations that result in increasing levels of resistance to the fluoroquinolones and to be transmitted from person to person.

Aged↗

Evolution of the simulated data problem.

The simulated data problem was designed via an interactive process by the Simulation Problem Organizing Committee and the selected data simulators. Based on discussions at the previous Genetic Analysis Workshop, many of the features of previous simulation problems, such as a complex disease, genome scan, and replication, were retained and in addition, a population genetics model was used to generate the simulated genes. We describe the process that was used to structure the problem and summarize the discussions about many of the scientific issues that were considered.

Chromosome Mapping↗

Pharmacologic therapy of persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn (PPHN) is a potentially life-threatening condition characterized by a failure of pulmonary vascular resistance to decrease adequately during the transition to extrauterine life. Inhaled nitric oxide, a vasodilator that acts selectively on the pulmonary circulation, has revolutionized the treatment of this condition. However, inhaled nitric oxide has not proven effective in all patients, particularly those with congenital diaphragmatic hernias or meconium aspiration syndrome. Furthermore, large clinical trials of inhaled nitric oxide have failed to demonstrate significant differences in mortality between nitric oxide-treated and control infants with PPHN. Other therapeutic approaches to PPHN have been limited by a relative lack of specificity for the pulmonary circulation, and have received much less attention. Pharmacologic approaches, including pulmonary surfactants, prostacyclin, endothelin antagonists, Ca(2+)-channel blockers, magnesium sulfate, and tolazoline, have exhibited varying degrees of efficacy in lowering pulmonary vascular pressures in humans and/or animals. A number of these agents are also effective when used in combination. For example, phosphodiesterase inhibitors have been reported to act synergistically with inhaled nitric oxide. Surfactants also appear to be useful in PPHN, particularly in patients with congenital diaphragmatic hernia, when used in combination with other therapies. Surfactant lavage and other novel therapies may also be effective in combination therapy of meconium aspiration syndrome. Further studies should be directed at defining the optimal therapies in specific clinical settings. Validation of multiple therapeutic modalities for PPHN, including inhaled nitric oxide, will allow for rational, combined vasodilator strategies that are specific for the underlying pathophysiology in each patient.

Anti-Inflammatory Agents↗

Phenotypic and genotypic characterization of macrolide-resistant group A Streptococcus strains in the province of Quebec, Canada.

Resistance to macrolides among group A streptococci is an increasing problem worldwide. We examined 496 strains phenotypically and genotypically for resistance to erythromycin and clindamycin. Strains were isolated in five different geographical areas representing about 45% of the total Quebec population. The overall resistance rate was 4.6% but varied from 0% in rural areas to 9.4% in Montreal. Of the 23 strains showing resistance to erythromycin, 15 (65%) had an identical pulsed-field gel electrophoresis pattern, were of serotype M28T28 and harboured the erm(TR) gene, suggesting the spread of a single clone. Of the remaining eight strains, two strains had the erm(B) gene, five had the mef gene and one with a different serotype also had the erm(TR) gene.

Anti-Bacterial Agents↗

In vitro activity of a novel ketolide ABT-773 against invasive strains of Streptococcus pneumoniae.

New ketolides such as ABT-773 are a promising group of antibiotics in an era of increasing antibiotic resistance. We tested 704 invasive strains of Streptococcus pneumoniae collected from 1990 to 1998. Overall resistance was 8.3, 4.6, 4.5 and 3.6% for penicillin, cefuroxime, erythromycin and clarithromycin, respectively. By using a recommended breakpoint for susceptibility of <0.5 mg/L, no strains showed reduced susceptibility to ABT-773. ABT-773 was very active against all penicillin-resistant strains (MIC > 2 mg/L, with a mean geometric mean <0.06 mg/L), and against all 33 erythromycin-resistant strains, irrespective of the mode of resistance [mef- or erm(B)-mediated]. ABT-773 is a very active and promising agent against invasive strains of S. pneumoniae, including multiresistant strains.

Anti-Bacterial Agents↗

A simple method for SC-cut resonator design.

This paper presents a design method utilizing simple semi-empirical equations for round, plano-convex SC-cut resonators. These equations were developed on the basis of experimental results collected over a long period relating SC-cut resonator design and performance covering a wide range of frequencies, radii of curvature, and plate diameters. The equations make possible the design of fundamental, third overtone, and fifth overtone resonators. An example calculation of resonator parameters and comparison with experimental results are also presented.

Journal Article↗

Developmental screening of children diagnosed with congenital heart defects.

Children with congenital heart disease (CHD) are more likely than normal children to have developmental delays. The development of 64 children with CHD less than 6 years old was screened with the Denver II. Thirty-five of the 64 children had CHD that required surgical or catheter intervention. These 35 children were significantly less likely than other children with CHD to be normal on developmental screening (46% vs 86%, respectively). Thirty-four percent of children with more severe CHD were referred for early intervention. As research shows the efficacy of early intervention, results indicate the need for early developmental evaluation of children with CHD of hemodynamic significance.

Analysis of Variance↗

Expression of Dlx genes during the development of the murine dentition.

The mammalian Dlx homeobox gene family has been shown to play multiple roles in tooth development, but a detailed comparison of the expression pattern of all members throughout tooth development has been lacking. We provide such an analysis for the six known murine Dlx genes. The expression patterns for these genes allow a refinement of previously proposed models for the role of Dlx genes in tooth type specification and raise the possibility of roles for subsets of these genes in tooth initiation, morphogenesis (enamel navel formation, enamel knot induction, cervical loop growth), and enamel formation. The relationship of Dlx gene expression to their genomic organization suggests coordinate regulation of linked genes at early stages but regulatory differences at later stages.

Animals↗

Comparative evaluation of the MB/BacT and BACTEC 460 TB systems for the detection of mycobacteria from clinical specimens: clinical relevance of higher recovery rates from broth-based detection systems.

New broth-based detection systems have higher recovery rates of mycobacteria from clinical specimens than traditional cultures on solid media. The clinical significance of this higher sensitivity rate is largely unknown. We prospectively evaluated the performances of two liquid media detection systems (the MB/BacT system and the BACTEC 460 TB system) and an egg-based Lowenstein-Gruft solid medium (LG) on the recovery rates of mycobacteria from 849 clinical specimens. Mycobacteria (other then M. gordonae) were detected in 51 (6.0%) specimens. In 12/51 (23%) specimens, mycobacteria (five mycobacterium tuberculosis (MtB) and seven non-M tuberculosis complex (MOTT) were recovered only from the broth-based systems. Review of the patients' clinical charts revealed that failure of LG to recover Mtb were due to nonmycobacterial overgrowth and antibiotic treatment. The recovered MOTT were all clinically nonsignificant. Higher sensitivity of broth-based mycobacteria detection systems is largely due to their capability to recover mycobacteria from treated tuberculous patients or from partially decontaminated specimens. The high recovery rates of nonclinically significant MOTT could potentially increase inappropriate use of antibiotics.

Bacterial Typing Techniques↗

Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease.

One hallmark of Alzheimer disease is the accumulation of amyloid beta-peptide in the brain and its deposition as plaques. Mice transgenic for an amyloid beta precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms of the human amyloid precursor protein, show many of the pathological features of Alzheimer disease, including extensive deposition of extracellular amyloid plaques, astrocytosis and neuritic dystrophy. Active immunization of PDAPP mice with human amyloid beta-peptide reduces plaque burden and its associated pathologies. Several hypotheses have been proposed regarding the mechanism of this response. Here we report that peripheral administration of antibodies against amyloid beta-peptide, was sufficient to reduce amyloid burden. Despite their relatively modest serum levels, the passively administered antibodies were able to enter the central nervous system, decorate plaques and induce clearance of preexisting amyloid. When examined in an ex vivo assay with sections of PDAPP or Alzheimer disease brain tissue, antibodies against amyloid beta-peptide triggered microglial cells to clear plaques through Fc receptor-mediated phagocytosis and subsequent peptide degradation. These results indicate that antibodies can cross the blood-brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders.

Alzheimer Disease↗

Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene.

This study evaluated the ability of gene transfer to enhance bone healing. Segmental defects were created surgically in the femora of New Zealand white rabbits. First generation adenoviruses were used as vectors to introduce into the defects genes encoding either human bone morphogenetic protein-2 (BMP-2) or, as a negative control, firefly luciferase. Representative specimens were evaluated histologically after 8 weeks. Healing of the defects was monitored radiographically for 12 weeks, after which time the repair tissue was evaluated biomechanically. By radiological criteria, animals receiving the BMP-2 gene had healed their osseous lesions after 7 weeks, whereas those receiving the luciferase gene had not. Histologic examination of representative rabbits at 8 weeks confirmed ossification across the entire defect in response to the BMP-2 gene, whereas the control defect was predominantly fibrotic and sparsely ossified. At the end of the 12-week experiment, the control femora still showed no radiological signs of stable healing. The difference in radiologically defined healing between the experimental and control groups was statistically significant (P < 0. 002). Biomechanical testing of the femora at 12 weeks demonstrated statistically significant increases in the mean bending strength (P < 0.005) and bending stiffness (P < 0.05) of the animals treated with the BMP-2 gene. Direct, local adenoviral delivery of an osteogenic gene thus led to the healing of an osseous lesion that otherwise would not do so. These promising data encourage the further development of genetic approaches to enhancing bone healing. Gene Therapy (2000) 7, 734-739.

Adenoviridae↗

Comparative activity of new quinolones against 326 clinical isolates of Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is an important emerging pathogen causing a variety of infections in severely ill patients. This microorganism is inherently resistant to many antibiotics, and only a few therapeutic options are available. The principal aim of this study was to assess the in vitro activity of new quinolones against this pathogen. Three hundred and twenty-six single clinical isolates were tested in this study. The MIC(90) was 16 mg/L for ciprofloxacin, 8 mg/L for levofloxacin and gatifloxacin, 4 mg/L for trovafloxacin, moxifloxacin and sparfloxacin and 2 mg/L for clinafloxacin. At a 2 mg/L concentration, a C(max) lung:MIC ratio of >/=10 can be reached for 95%, 84.3%, 83.1% and 81.5% of isolates, respectively, for clinafloxacin, trovafloxacin, moxifloxacin and sparfloxacin (P < 0. 001 compared with levofloxacin and ciprofloxacin). In spite of the rare but serious adverse events associated with the new-generation quinolones, these agents may become very useful in the treatment of certain severe or life-threatening infectious conditions due to S. maltophilia, notably lower respiratory tract infections.

4-Quinolones↗

Antarctica natural laboratory and space analogue for psychological research.

This introduction to the special issue traces the history of psychosocial concerns related to Antarctic exploration, from the heroic age of early explorers through the International Geophysical Year (IGY) of 1957 to 1958 to recent and current systematic research projects. The introduction discusses the organization and topics of international psychological investigations in polar stations and summarizes the articles that follow. Living in Antarctica imposes some unusual restrictions as well as opportunities, and it requires psychological adaptation to extreme environmental circumstances. The thrust of previous scientific and popular literature has been to focus on the negative effects of the situation and ignore the positive ones; however, ongoing studies are bringing about a more balanced view. Having an accurate understanding is important not only intrinsically and for appropriate application in the Antarctic itself but also in analogous extreme and unusual environments. These include extended space flight and space habitation, such as the projected voyage to Mars.

Adaptation, Psychological↗

Psychological adjustment during three Japanese Antarctic research expeditions.

This study investigates the individual characteristics of Japanese polar team members. Four sets of measures from the Polar Psychology Project Battery have been used in Asuka Station. These measures are thought to reflect adjustment and well-being. Data have been collected during 3 consecutive years. The psychological profile of the subjects was relatively stable, and comparable to the standard means of Western sojourners. The results show the subjects were generally high in stress resistance. However, an increase in the Planning Orientation score and a decrease in the Hardiness score appear at the end of the wintering-over. These modifications correspond to psychological changes linked to the approaching end of wintering-over.

Adaptation, Psychological↗

Delivery room management of the apparently vigorous meconium-stained neonate: results of the multicenter, international collaborative trial.

OBJECTIVE: Disagreement exists concerning the appropriate delivery room management of the airway of vigorous meconium-stained infants. Some suggest a universal approach to intubation and suctioning of the airway in all such neonates, whereas others advocate a selective approach. We performed this investigation: 1) to assess whether intubation and suctioning of apparently vigorous, meconium-stained neonates would reduce the incidence of meconium aspiration syndrome (MAS); and 2) to determine the frequency of complications from delivery room intubation and suctioning of such infants. METHODS: Inclusion criteria included: 1) gestational age >/=37 weeks; 2) birth through meconium-stained amniotic fluid of any consistency; and 3) apparent vigor immediately after birth. Subjects were randomized to be intubated and suctioned (INT) or to expectant management (EXP). Primary outcome measures included: 1) the incidence of respiratory distress, including MAS, and 2) the incidence of complications from intubation. RESULTS: A total of 2094 neonates were enrolled from 12 participating centers (1051 INT and 1043 EXP). Meconium-stained amniotic fluid consistency was similar in both groups. Of the 149 (7.1%) infants that subsequently demonstrated respiratory distress, 62 (3.0%) had MAS and 87 (4.2%) had findings attributed to other disorders. There were no significant differences between groups in the occurrence of MAS (INT = 3.2%; EXP = 2.7%) or in the development of other respiratory disorders (INT = 3.8%; EXP = 4.5%). Of 1098 successfully intubated infants, 42 (3.8%) had a total of 51 complications of the procedure. In all cases, the complications were mild and transient in nature. CONCLUSIONS: Compared with expectant management, intubation and suctioning of the apparently vigorous meconium-stained infant does not result in a decreased incidence of MAS or other respiratory disorders. Complications of intubation are infrequent and short-lived.

Adult↗