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Biomedical subjects

K Peters

Publications and source records attributed to K Peters.

At least 127 records · Page 7Linked to original sources
PubMed2001

Use of individualized versus standard criteria to identify abnormal levels of heart rate or oxygen saturation in preterm infants.

Preterm infants' physiological indicators, such as heart rate, respiratory rate, and oxygen saturation levels, are routinely monitored by devices that can alert nurses to threatening changes in condition. Most Neonatal Intensive Care Units use standard criteria as alerting algorithms to determine when an alert should be issued, and these standard criteria have been adopted uncritically in studies of preterm infants. This article presents results from a study examining preterm infants' physiological responses to a gentle human touch (GHT) intervention in which we compared the use of standard and individualized criteria to define the percentages of abnormally low and high heart rates (HRs) and abnormally low oxygen saturation (O2 sat) levels before, during, and after periods of GHT. Results indicated that there were no differences in the percentages of abnormal HRs or O2 sat values between periods using standard criteria. However, using individualized criteria, there were significantly greater percentages of abnormally low heart rates and O2 sat levels during and after GHT periods as compared to baseline periods. The findings suggest that standard criteria may not be sensitive enough to detect subtle physiological responses to environmental stimuli such as touch. Moreover, consistent with the recognition of the value of individualized developmental care, these results suggest that the clinical effectiveness of individualized criteria for setting monitor alert limits merits further investigation.

Blood Gas Analysis↗
PubMed2001

A new class of potent reversible inhibitors of metallo-proteinases: C-terminal thiol-peptides as zinc-coordinating ligands.

A number of substrate analogous peptides containing a phosphoramidate, phosphonate ester, hydroxamate, carboxylate or sulfhydryl group are known to be inhibitors of thermolysin and other metalloproteinases. According to the specificity, most of the inhibitors mimic the prime site of the active center. Hitherto, peptidyl derivatives with a thiol group at the C-terminus have not been described. We have synthesized the protected cysteamides Ac-Ala-Ala-CA-SH and Z-Aa1-Aa2-CA-SH (Aa1: Ala, Pro; Aa2: Ala, Leu). The binding of these thiol peptide inhibitors to the metalloproteinases is characterized first by the coordination of the thiolate group of the inhibitor to the catalytic zinc ion and second by the subsite interaction of the peptide ligand in the active site of the enzyme. All peptide derivatives were competitive inhibitors of the zinc metalloproteinase thermolysin. The strongest inhibition was found with Z-Pro-Leu-CA-SH (Ki = 30 microM). Substitution of the N-protecting benzyloxycarbonyl residue towards the acetyl group in the peptide inhibitor, the inhibition constant decreased about 25 times.

Binding Sites↗
PubMed2000

Stimulation of mouse bone marrow cells with kit ligand, FLT3 ligand, and thrombopoietin leads to efficient retrovirus-mediated gene transfer to stem cells, whereas interleukin 3 and interleukin 11 reduce transduction of short- and long-term repopulating cells.

The effects of cytokine stimulation during retroviral transduction on in vivo reconstitution of mouse hematopoietic stem cells was tested in a murine competitive repopulation assay with alpha-thalassemia as a marker to distinguish donor and recipient red blood cells (RBCs) and the enhanced green fluorescent protein (EGFP) as a marker for gene transfer. After transplantation, EGFP was detected in up to 90% of circulating RBCs, platelets, and leukocytes, and in primitive progenitors in bone marrow (BM), spleen, and thymus of individual transplanted mice for observation periods of more than 6 months. Large quantitative differences in reconstitution were observed after transplantation with graded numbers (1000-30, 000) of EGFP(+) cells preconditioned with various combinations of Kit ligand (KL), FLT-3 ligand (FL), thrombopoietin (TPO), interleukin 3 (IL-3), and IL-11. Relative to nonmanipulated BM cells, repopulation of EGFP(+) cells was maintained by KL/FL/TPO stimulation, but approximately 30-fold reduced after KL/FL/TPO/IL-3, or KL/FL/IL-3/IL-11. These differences were not caused by changes in the ability of immature hematopoietic cells to home to the BM, which was only moderately reduced. In conclusion, these quantitative transplantation studies of mice demonstrate the importance of optimal ex vivo cytokine stimulation for gene transfer to stem cells with retention of their in vivo hematopoietic potential, and also emphasize that overall in vitro transduction frequency does not predict gene transfer to repopulating stem cells.

3T3 Cells↗
PubMed2000

Asymptomatic laryngeal malformations are common in patients with Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS) comprises hypothalamic hamartoma, polydactyly, pituitary dysfunction, laryngotracheal cleft, imperforate anus, and other anomalies. Some patients with PHS have a bifid epiglottis, a rare malformation. Greig cephalopolysyndactyly syndrome (GCPS) comprises polydactyly with craniofacial malformations without the PHS malformations. Both disorders are caused by mutations in the GLI3 gene. Laryngoscopy on 26 subjects with PHS showed that 15 had a bifid or cleft epiglottis (58%) and none of 14 subjects with GCPS had a cleft epiglottis. The malformed epiglottis was asymptomatic in all of the prospectively evaluated subjects. One additional PHS subject was found to have bifid epiglottis and a posterior laryngeal cleft on autopsy. We conclude that bifid epiglottis is common in PHS but not GCPS. Posterior laryngeal clefts are an uncommon manifestation of PHS and are identified only in severely affected patients. The diagnosis of a bifid epiglottis should prompt a thorough search for other sometimes asymptomatic anomalies of PHS to provide better medical care and recurrence risk assessment for affected individuals and families.

Adolescent↗
PubMed2000

Violene/cyanine hybrids as electrochromics part 2: tetrakis(4-dimethylaminophenyl)ethene and its derivatives

The general structure of violene/cyanine hybrids (see below) is exemplified by tetrakis(4-dimethylaminophenyl)ethene 1(RED) its vinylogue 2(RED) and its diazavinylogue 3(RED). As judged from their cyclic voltammograms and spectroelectrograms, oxidation occurs perfectly reversible by loss of two electrons creating closed shell systems 1-3(OX)+2 with strong bathochromic shifts (Michlers hydrol blue moieties). ESR spectra indicate only minor amounts of radical cations. At much higher potentials by another reversible loss of two electrons (-->1-3(OX)+4) the long wavelengths absorptions are replaced by shorter ones. In system 4, containing two 4-dimethylaminophenyl units only, the violene character is better preserved since oxidation occurs stepwise by single electron transfer up to 4(OX)+4. These results are backed by theoretical calculations for 1-4, demonstrating the strong geometrical differences between the various oxidation levels. Besides, new types of cyclic structures for 1-4(OX)+4 are indicated by these calculations: For systems 1-3 cyclic structures for tetracations have been found to be more stable by 3-20 kcalmol(-1) than acyclic structures, whereas for system 4 the acyclic structure is more stable by about 22 kcalmol(-1). The redox behavior of systems 1-4 is of general importance for electrochromic systems.

Journal Article↗
PubMed2000

New oxidative transformations of phenolic and indolic oxazolines: an avenue to useful azaspirocyclic building blocks.

The oxidative cyclization of a phenolic amide to a spirolactam has long been regarded as an "impossible" reaction, because exposure of the substrates to a variety of oxidants results in formation of spirolactones with consequent loss of the amine segment. We recently communicated that this heretofore unknown transformation may be achieved by oxidation of oxazoline analogues of phenolic and indolic amides. Herein, we provide full details of our work.

Azo Compounds↗
PubMed2000

A high-performance liquid chromatographic method to measure sphingosine 1-phosphate and related compounds from sphingosine kinase assays and other biological samples.

Sphingosine 1-phosphate is an intermediate of sphingosine catabolism as well as a potent signaling compound. Conditions were established for the extraction and analysis of sphingosine 1-phosphate and other sphingoid base 1-phosphates from in vitro sphingosine kinase assays and other biological samples. The sphingoid base 1-phosphates were extracted in high yield (85%) using small C-18 reverse-phase columns (LiChroprep RP-18). After the extracts were treated with 0.1 N KOH to remove glycerolipids, the sphingoid base 1-phosphates were converted to fluorescent o-phthalaldehyde derivatives that were separated by HPLC using C-18 columns with a mobile phase of methanol:10 mM potassium phosphate (pH 7.2):1 M tetrabutylammonium dihydrogen phosphate (in water) (83:16:1, v/v/v). The o-phthalaldehyde derivative of sphingosine 1-phosphate was reasonably stable (t(1/2) > or = 18 h) when EDTA was present and could be detected in picomole amounts. The HPLC retention time of the sphingoid base 1-phosphates could be shifted by adjusting the mobile phase to pH 5.5, which is useful in separating overlapping compounds (such as sphingosine 1-phosphate and 4-D-hydroxysphinganine) and in confirming the identity of sphingoid base 1-phosphates in biological samples. The extraction procedure and HPLC method facilitated assays of sphingosine kinase with different sphingoid bases as substrates and/or inhibitors and enabled the quantitation of sphingoid base 1-phosphates in human plasma, serum, and platelets as well as in strains of Saccharomyces cerevisae with mutations in sphingolipid metabolism.

Blood Platelets↗
PubMed2000

Opposite pi-face selectivity for the DMD and m-CPBA epoxidations of chiral 2,2-dimethyloxazolidine derivatives of tiglic amides: control by steric interactions versus hydrogen bonding

[formula: see text] A high extent but opposite sense in the diastereoselectivity has been observed for the DMD and m-CPBA epoxidations of the optically active tiglic amides (S)-1 with 2,2-dimethyloxazolidines as chiral auxiliaries. This unprecedented reversed pi-facial differentiation for these two peroxidic oxidants is rationalized in terms of like (lk) and unlike (ul) transition structures: For DMD, steric interactions dominate, such that the unlike transition structure is favored, while for m-CPBA, hydrogen-bonding effects overcome these steric repulsions and the like one is preferred.

Journal Article↗
PubMed2000

[Focal paroxysmal atrial fibrillation. Experiences with treatment using high frequency catheter ablation].

BACKGROUND AND OBJECTIVE: As has recently been discovered, paroxysmal atrial fibrillation (PAF) can be induced by focal extrasystoles or tachycardia. This raises the question of whether this form of atrial fibrillation can be cured by high-frequency catheter ablation of the focal trigger. PATIENTS AND METHODS: Seven men and eleven women (mean age 45.6 +/- 11 years) with severe symptoms and treatment-resistant PAF underwent electrophysiological tests with the aim of high-frequency catheter ablation, if long-term ECG monitoring had demonstrated frequent atrial extrasystoles or tachycardia as pointer to a focal origin. Ablation was performed at the point of earliest excitation after the origin of the ectopic focus had been localized. The end-point was reached if the atrial ectopic rhythm had ceased for more than 60 min. RESULTS: In 18 of the 20 patients an ectopic focus was found and successfully ablated (1 in the superior vena cava, 3 in the right atrium and 16 in a pulmonary vein). Atrial ectopic beats recurred within 24 hours of ablation in 6 of the 14 patients with a pulmonary vein focus: a second focus was found in two, re-emergence of the original focus in two, no re-investigation in another two. 13 of the 18 patients have had no further symptoms after a mean follow-up of 11 months without anti-arrhythmia treatment. CONCLUSION: The results indicate that focally induced paroxysmal atrial fibrillation can be cured by locally applied high-frequency ablation.

Atrial Fibrillation↗
PubMed2000

Genetic aberrations common in gastric high-grade large B-cell lymphoma.

Genetic aberrations associated with the development of extranodal high-grade large B-cell lymphoma originating in the stomach have not been fully identified yet. We analyzed 31 such lymphomas using 73 microsatellite markers for allelic imbalance and microsatellite instability. The highest frequency (42%) of loss of heterozygosity (LOH) was found on the long arm of chromosome 6. We identified 2 LOH hot spots on 6q21-22.1 and 6q23.3-25, flanked by markers D6S246-D6S261 and D6S310-D6S441, respectively, containing putative tumor suppressor genes (TSGs). These 6q aberrations were found to be the sole allelic imbalance in 1 patient only; they were mostly accompanied by additional abnormalities. Several known TSGs, namely, the APC, p15/p16, p53, and DCC genes, were found to suffer frequent LOH during lymphomagenesis. LOH was also detected in regions containing putative TSGs on 7q and 13q14. Frequent amplification of genomic material was found in the 2p, 3q27 at the BCL-6 gene locus, 6p, 7q, 11q23-24 at the MLL gene locus, and 18q regions. Analysis of the pattern of occurrence of these aberrations revealed an association of the amplification of the MLL gene region with LOH at the p53 locus (P =.02). Only low frequency of microsatellite instability (MSI) was detected in these lymphomas and MSI incidence increased with age (P =.01). Karyotypic instability thus plays the main role in the development of gastric high-grade large B-cell lymphoma. Common genetic aberrations responsible for lymphomagenesis are deletions of 6q, loss of p53, and amplification of the 3q27 and the MLL gene regions. (Blood. 2000;95:1180-1187)

Age Factors↗
PubMed2000

Recurrent genetic aberrations in thymoma and thymic carcinoma.

Apart from single reported aberrant karyotypes, genetic alterations in thymic epithelial neoplasms have not been investigated so far. In this study, 12 World Health Organization classification type A thymomas (medullary thymomas), 16 type B3 thymomas (well-differentiated thymic carcinomas), and nine type C thymomas, all of them primary thymic squamous cell carcinomas, were analyzed by comparative genomic hybridization and fluorescence in situ hybridization. With the exception of one single case, type A thymomas did not reveal chromosomal gains or losses in comparative genomic hybridization. In contrast, all type B3 thymomas showed chromosomal imbalances, with gain of 1q, loss of chromosome 6, and loss of 13q occurring in 11 (69%), six (38%), and five (31%) of 16 cases, respectively. In primary thymic squamous cell carcinoma, the most frequent chromosomal losses were observed for 16q (six of nine cases, 67%), 6 (4 of 9, 44%), and 3p and 17p (three of nine each, 33%), whereas recurrent gains of chromosomal material were gains of 1q (5 of 9, 56%), 17q, and 18 (three of nine each, 33%). This study shows that the distinct histological thymoma types A and B3 exhibit distinct genetic phenotypes, whereas type B3 thymoma and primary thymic squamous cell carcinoma partially share genetic aberrations. In addition to the possible tumorigenic role, the deletion in type B3 thymoma of chromosome 6, harboring the HLA locus, might play a role in the pathogenesis of paraneoplastic autoimmunity characteristic of thymoma.

Adult↗
PubMed2000

6-Hydroxyluteolin-7-O-(1''-alpha-rhamnoside) from Vriesea sanguinolenta Cogn. and Marchal (Bromeliaceae).

The isolation of 6-hydroxyluteolin-7-O-(1"-alpha-rhamnoside) from the Central American epiphyte Vriesea sanguinolenta Cogn. and Marchal (Bromeliaceae) is described here. Its stereostructure was established by spectroscopic methods and an X-ray structure analysis of its hepta-O-acetyl derivative. This flavonoid glycoside had previously been reported from some Teucrium species (Labiatae), yet without sufficient physical data and spectroscopic evidence.

Animals↗
PubMed2000

Bromal-derived tetrahydro-beta-carbolines as neurotoxic agents: chemistry, impairment of the dopamine metabolism, and inhibitory effects on mitochondrial respiration.

The mammalian alkaloids tryptoline (1) and eleagnine (2) as well as the highly halogenated (X = F, Cl, Br) tetrahydro-beta-carbolines (THbetaCs) 3-5, structurally similar to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 6), were found to have a common feature of inducing a severe impairment of the nigrostriatal dopamine metabolism and inhibiting complex I of the mitochondrial respiratory chain highly selectively. Within the series of compounds tested, 1-tribromomethyl-1,2,3,4-tetrahydro-beta-carboline ('TaBro', 5), which was prepared in high yields from the biogenic amine tryptamine ('Ta', 7) and the unnatural aldehyde bromal ('Bro', 8) by a Pictet-Spengler cyclization reaction, turned out to be the most potent toxin in vitro and in vivo. As demonstrated by voltammetric measurements on rats, for all the THbetaCs 1-5 investigated, intranigral application of a single dose of 10 microg resulted in a significant reduction of the dopaminergic activity in the striatum, with the strongest effect being observed for TaBro (5). Using rat brain homogenates, again 5 (IC50 = 200 microM) as well as its dehydrohalogenation product 11 (IC50 = 150 microM) exhibited the most pronounced inhibitory potential on mitochondrial respiration. The halogen-free THbetaCs 1 and 2 as well as the MPTP metabolite 1-methyl-4-phenylpyridinium ion (MPP+), by contrast, showed only a moderate inhibition at concentrations in the millimolar range (e.g. for MPP+: IC50 = 3.5 mM). For an elucidation of the role of hydrophobic portion in the inhibitory action against complex I activity, several N-acyl derivatives (15-21) of 5 were synthesized and tested. An X-ray diffraction study on the 3-dimensional structure of trifluoroacetylated highly halogenated THbetaCs (12-14) revealed the tetrahydropyrido part to adopt a nearly planarized half-chair conformation. Because of the steric demand of the trihalogenmethyl moiety (CF3 < CCl3 < CBr3), the N-substituent is dramatically pushed out of that ring 'plane'.

Animals↗
PubMed2000

The resistance to physiological shear stresses of the erythrocytic rosettes formed by cells infected with Plasmodium falciparum.

Rosetting forces are believed to be an important contributor to the microcirculatory obstruction that occurs in malaria caused by Plasmodium falciparum. In this study, rosettes of erythrocytes from cultures of this parasite were suspended in different media and exposed to shear stresses corresponding to those encountered on the arterial and venous sides of the human circulation. The rosettes formed by infected erythrocytes in malaria culture medium containing 10% AB serum were disrupted easily (approximately 50% being broken) when exposed to very low shear stresses of < 0.5 Pa. However, use of higher concentrations of serum strengthened the rosetting binding forces considerably. Suspension of rosettes in a viscous colloid (e.g. dextran) increased the adherence forces between infected and uninfected red cells. The results indicate that rosettes do resist the physiological shear forces that are encountered in the venular side of the circulation and could thus contribute to microvascular obstruction in falciparum malaria.

Culture Media↗
PubMed2000

Preparation of a clofazimine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine Mycobacterium avium infection.

Clofazimine nanosuspensions were produced by high pressure homogenization and the formulation was optimized for lyophilization. Characterization of the product by photon correlation spectroscopy, laser diffraction and Coulter counter analysis showed that the clofazimine nanosuspensions were suitable for iv injection with a particle size permitting passive targeting to the reticuloendothelial system. Following iv administration to mice of either the nanocrystalline or a control liposomal formulation at a dose of 20 mg clofazimine/kg bodyweight, drug concentrations in livers, spleens and lungs reached comparably high concentrations, well in excess of the MIC for most Mycobacterium avium strains. When C57BL/6 mice were experimentally infected with M. avium strain TMC 724, nanocrystalline clofazimine was as effective as liposomal clofazimine in reducing bacterial loads in the liver, spleen and lungs of infected mice. Nanocrystalline suspensions of poorly soluble drugs such as riminophenazines are easy to prepare and to lyophilize for extended storage and represent a promising new drug formulation for intravenous therapy of mycobacterial infections.

Animals↗
PubMed2000

Detection of occult pneumothoraces on abdominal computed tomographic scans in trauma patients.

BACKGROUND: An unrecognized, or occult, injury is particularly dangerous in trauma patients, who often have multiple life-threatening injuries. We sought to determine the frequency and quantify the utility of the abdominal computed tomographic (CT) scan in detecting occult pneumothoraces. METHODS: Charts of all trauma patients diagnosed with a pneumothorax over a 7-year period were retrospectively reviewed for findings on admission chest radiograph, abdominal CT scan, and other demographic data. RESULTS: A total of 312 charts were reviewed, with 230 patients identified as having a pneumothorax at admission. Of the 230 patients, 126 (54.8%) had an occult pneumothorax identified on abdominal CT scan. In these patients, the mean Trauma Score was 14.1 +/- 2.9 and the mean Injury Severity Score was 24.1 +/- 11.2. In the group of occult pneumothoraces, 84 (66.7%) underwent chest tube placement. CONCLUSIONS: Abdominal CT scanning provided important information about thoracic trauma often missed on initial evaluation in the trauma bay. This information frequently affected the patient's clinical management.

Abdominal Injuries↗
PubMed2000

Genetic imbalances in primary gastric diffuse large B-cell lymphomas: comparison of comparative genomic hybridization, microsatellite, and cytogenetic analysis.

Extranodal malignant non-Hodgkin's lymphomas account for about 40% of lymphoid neoplasms, but few data are available concerning the genetic background of primary gastric diffuse large B-cell lymphoma (DLBCL). A study was performed of 27 primary gastric DLBCLs and 5 gastric DLBCLs with a concomitant low grade component of mucosa-associated lymphoid tissue-type lymphoma using comparative genomic hybridization (CGH), microsatellite studies, classic cytogenetics, and fluorescence in situ hybridization (FISH) to search for specific genetic aberrations. The most frequent aberrations were losses of material on chromosome 6q and gains of parts of chromosome 3. In three cases, a total of six high level DNA amplifications were detected, with five of them involving chromosomal regions not having been reported before in gastric DLBCL. A high overall concordance of 91.4% between microsatellite analysis and CGH was observed using DNA extracted from the same tissue block. The concordance achieved using DNA from different tissue blocks of the same patient was 85%. Microsatellite studies, CGH, FISH, and classic cytogenetics represent complementary techniques that facilitate a comprehensive view of genetic alterations in malignancies such as primary gastric DLBCL.

Adult↗