Somatoform deception.
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Attitude of Health Personnel↗
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Automatic scanning of interphase FISH for prenatal diagnosis in uncultured amniocytes.
Fluorescence in situ hybridization (FISH) of uncultured amniocytes using chromosome-specific DNA probes offers the opportunity for rapid aneuploidy screening. Between 80 and 95% of all chromosomal disorders expected in the second trimester of pregnancy can be discovered within 24 hr if DNA probes specific for chromosomes 21, 18, 13, X, and Y are used. Rapid results are crucial for clinical decision-making and are helpful in decreasing the anxiety level in most patients. One of the major factors that have been preventing the rapid FISH test from being broadly incorporated into the clinical setting is the limited staff in the cytogenetics laboratories. The present study demonstrates the use of an automated scanning system (Duet, BioView Ltd. Rehovot, Israel) for analyzing FISH in uncultured amniocytes. Fifty-six amniotic fluid samples were evaluated in parallel by karyotyping, manual FISH analysis, and automatic FISH scanning. Automatic scanning provided accurate results compared to both manual FISH scoring and karyotype analysis. The correlation between automatic and manual FISH scanning was found to be very high (r = 0.9, p < 0.0001). The availability of automation for aneuploidy screening in amniotic fluid samples will enable offering this test to a broader patient population while providing fast and reliable results.
Amnion↗
Vecuronium and atracurium in patients with end-stage renal failure. A comparative study.
Twenty patients with end-stage renal failure, undergoing kidney transplantation, were assigned randomly to receive either vecuronium or atracurium under evoked twitch tension control. The cumulative-dose technique was used to obtain 95% twitch depression (vecuronium: initial bolus 15 micrograms kg-1, increments 6 micrograms kg-1; atracurium: initial bolus 100 micrograms kg-1, increments 40 micrograms kg-1). Using ED95 values derived from the log-probit dose-response curves, vecuronium was 4.6 times more potent than atracurium. The durations of action of the initial cumulative-doses (from end of injection of the last increment to 25% recovery) were 11.1 +/- 3.3 min for vecuronium and 16.2 +/- 3.9 min for atracurium (P less than 0.05). In terms of duration of action of the maintenance doses (vecuronium one-quarter of the total incremental dose; atracurium one-third) some cumulation was observed with vecuronium (interaction time X treatment; cumulation ratio 1.46 +/- 0.31 v. 0.98 +/- 0.10 for atracurium, P less than 0.001). After 2 h of surgery, the mean recovery times (25% to 75% twitch height) did not differ (18.5 +/- 2.8 min and 16.7 +/- 4.4 min). It is concluded that vecuronium might be less safe than atracurium in patients with end-stage renal failure undergoing prolonged operations.
Adult↗
Sedation caused by clonidine in patients with spinal cord injury.
BACKGROUND: In patients with spinal cord injury, cephalad spread of intrathecal (i.t.) medication could be delayed. METHODS: We used bispectral index and an observer scale to assess sedation after two different doses of i.t. clonidine in patients with or without spinal cord injury. Twelve patients with neurological deficit caused by trauma (Spinal Cord Injury, SCI) were compared with patients without neurological disease. They received 10 mg of i.t. bupivacaine with clonidine, with either 50 microg (low dose, n=6) or 150 microg (high dose, n=6) at L(2)-L(3). A further 12 patients, six with spinal trauma lesion and six healthy, received i.t. bupivacaine and 150 micro g of i.m. clonidine. RESULTS: Sedation and a decrease in BIS occurred only in patients receiving 150 microg of clonidine. Onset of sedation and the decrease in BIS was delayed in most spinal cord injured patients whatever the route of administration (P<0.001). Duration of sedation was not different between the groups. Delayed sedation and decrease of BIS after i.t. clonidine in patients with spinal cord injury are similar than those observed after i.m. clonidine. CONCLUSION: A systemic effect is likely to be the main reason for sedation.
Adrenergic alpha-Agonists↗
Immunological and spectroscopic studies of poly(dG-dC).poly(dG-dC) modified by cis-diamminedichloroplatinum(II).
The conformational changes induced by the binding of cis-diamminedichloroplatinum(II) to poly(dG-dC).poly(dG-dC) have been studied by reaction with specific antibodies, by circular dichroism and 31P nuclear magnetic resonance. Polyclonal and monoclonal antibodies to Z-DNA bind to platinated poly(dG-dC).poly(dG-dC) at low and high ionic strength. Antibodies elicited in rabbits immunized with the platinated polynucleotide bind to double stranded polynucleotides known to adopt the Z-conformation. At low and high ionic strength the circular dichroism spectrum of platinated poly(dG-dC).poly(dG- dC) does not resemble that of poly(dG-dC).poly(dG-dC) (B or Z conformation). At low ionic strength, the characteristic 31P nuclear magnetic resonance spectrum of the Z-form is not detected. It appears only at high ionic strength, as a component of a more complex spectrum.
Circular Dichroism↗
Electron microscopic measurement of chain flexibility of poly(dG-dC).poly(dG-dC) modified by cis-diamminedichloroplatinum(II).
The antitumor drug cis-diamminedichloroplatinum (II) (cis-Pt) forms bidentate adducts with guanine residues of poly(dG-dC).poly(dG-dC). The secondary structure of the polymer is altered. In this work, high resolution pictures of naked molecules, obtained by dark field electron microscopy reveal DNA chain distortions with radii as small as 30 A. The extent of distortion increases with the drug/nucleotide ratio (rb). These alterations of the secondary structure are responsible for the apparent shortening of the molecules. Measurements of the persistence lengths of the polymer as well as the end-to-end distances of elementary segments of various lengths, are obtained from digitized electron micrographs. The measurements are used to monitor and quantify the observed modifications of polymer structure upon cis-Pt binding at various rb or incubation times. Poly(dG-m5dC).poly(dG-m5dC) in the B and Z forms have different persistence lengths. In the B form, this polymer is more altered by cis-Pt than in the Z one.
Cisplatin↗
Characterization of the ternary complexes formed in the reaction of cis-diamminedichloroplatinum (II), ethidium bromide and nucleic acids.
The purpose of this study was to characterize the ternary complexes formed in the reaction of cis-diamminedichloroplatinum (II) (cis-DDP) and nucleic acids, in the presence of the intercalating compound ethidium bromide (EtBr). In these ternary complexes, some EtBr is tightly bound to the nucleic acids. Tight binding is defined by resistance to extraction with butanol, assayed by filtration at acid pH or thin layer chromatography at basic pH. These ternary complexes are formed with double stranded but not with single stranded nucleic acids. They are not formed if cis-DDP is replaced by transdiamminedichloroplatinum(II). The amount of tightly bound EtBr depends upon the sequence of the nucleic acid, being larger with poly (dG-dC).poly(dG-dC) than with poly(dG).poly(dC). Spectroscopic results support the hypothesis that the tight binding of the dye is due to the formation of a bidentate adduct (guanine-EtBr)cis-platin. The visible spectrum of the ternary complexes is blue-shifted as compared to that of EtBr intercalated between the base pairs of unplatinated DNA and it depends upon the conformation of the ternary complex. The fluorescence quantum yield of the ternary complexes is lower than that of free EtBr in water. Tightly bound EtBr stabilizes strongly the B form versus the Z form of the ternary complex poly(dG-dC)-Pt-EtBr and slows down the transition from the B form towards the Z form. The sequence specificity of cis-DDP binding to a DNA restriction fragment in the absence or presence of EtBr is mapped by means of the 3'----5' exonuclease activity of T4 DNA polymerase. In the absence of the dye, all the d(GpG) sites and all the d(ApG) sites but one in the sequence d(TpGpApGpC) are platinated. The d(GpA) sites are not platinated. In the presence of EtBr, some new sites are detected. These results might help to explain the synergism for drugs used in combination with cis-DDP and in the design of new chemotherapeutic agents.
Chemical Phenomena↗
Formation of a DNA monofunctional cis-platinum adduct cross-linking the intercalating drug N-methyl-2,7-diazapyrenium.
Our purpose was to better understand the mutual influence of cis-diamminedichloroplatinum (II) (cis-DDP) and intercalating drugs in their interactions with DNA. The present study deals with the intercalating drug N-methyl-2,7-diazapyrenium (MDAP). Two sets of experiments have been performed. In one set, the reaction between cis-DDP and nucleic acid was carried out in the presence of MDAP. The main adduct is a guanine residue chelated by platinum to a MDAP residue. It has the same spectroscopic properties as the synthesized compound cis-[Pt (NH3)2 (N7-d-guanosine) (N7-MDAP)] , the structure of which has been determined by 1H NMR. This adduct was only formed with double-stranded nucleic acids which reveals the importance of DNA matrix in orienting favorably the reactants. In the second set of experiments, the triamine complex cis-[Pt(NH3)2 (MDAP)CI]++ was reacted with the nucleic acids. At molar ratios drug over nucleotide residue equal or less than 0.10, all the added triamine complexes bind by covalent coordination to double-stranded nucleic acids. With natural DNA, the major adduct is cis-[Pt(NH3)2(d-guanosine) (MDAP)] . Thus the same adduct is formed on one hand in the reaction between DNA, MDAP and cis-DDP and on the other hand in the reaction between the triamine complex and DNA. The triamine complex offers the possibility to study the biological role of the new adduct.
Cisplatin↗
Base sequence-independent distorsions induced by interstrand cross-links in cis-diamminedichloroplatinum (II)-modified DNA.
Physico-chemical and immunological studies have been done in order to further characterize the distorsions induced in DNA by the interstrand cross-links formed between the antitumor drug cis-diamminedichloroplatinum (II) (cis-DDP) and two guanines on the opposite strands of DNA at the d(GC/GC) sites. Bending (45 degrees) and unwinding (79 +/- 4 degrees) were determined from the electrophoretic mobility of multimers of 21- 24-base pairs double-stranded oligonucleotides containing an interstrand cross-link in the central sequence d(TGCT/AGCA). The distorsions induced by the interstrand cross-link in the three 22-base pairs oligonucleotides d(TGCT/AGCA), d(AGCT/AGCT) and d(CGCT/AGCG) were compared by means of gel electrophoresis, circular dichroism, phenanthroline-copper footprinting and antibodies specifically directed against cis-DDP interstrand cross-links. The four different technical approaches indicate that the distorsions are independent of the chemical nature of the base pairs adjacent to the interstrand cross-link. The general conclusion is that the interstrand cross-link induces a bending and in particular an unwinding larger than other platinum adducts and the distorsions are independent of the nature of the bases (purine or pyrimidine) adjacent to the d(GC/GC) site.
Base Sequence↗
Rearrangement of interstrand cross-links into intrastrand cross-links in cis-diamminedichloroplatinum(II)-modified DNA.
In the reaction of the anticancer drug cis-diamminedichloroplatinum(II) (cis-DDP) with DNA, bifunctional intrastrand and interstrand cross-links are formed. In this work, we show that at 37 degrees C interstrand cross-links (ICL) are labile and rearrange into intrastrand cross-links. The ICL instability was first studied with a 10 base pairs (bp) double-stranded oligonucleotide containing a unique site-specific ICL resulting from chelation of the N7 position of two guanine residues on the opposite strands of DNA at the d(GC/GC) site by a cis-diammineplatinum(II) residue. The bonds between the platinum and the N7 of guanine residues within the interstrand adduct are cleaved. In 50 mM NaCl or NaClO4, this cleavage results in the formation of monofunctional adducts which subsequently form intrastrand cross-links. One cleavage reaction takes place per cross-linked duplex in either of both DNA strands. Whereas the starting cross-linked 10 bp duplex is hydrogen bonded, the two complementary DNA strands separate after the cleavage of the ICL. Under these conditions, the cleavage reaction is irreversible allowing its rate measurement (t1/2= 29+/-2 h) and closure of monofunctional adducts to intrastrand cross-links occurs within single-stranded DNA. Within a longer cross-linked oligonucleotide (20 bp), ICL are apparently more stable (t1/2= 120+/-12 h) as a consequense of monofunctional adducts closure back to ICL. We propose that the ICL cleavage is reversible in DNA and that these adducts rearrange finally into intrastrand cross-links. Our results could explain an 'ICL unhooking' in previously reported in vivo repair studies [Zhenet al. (1993)Carcinogenesis14, 919-924].
Antineoplastic Agents↗
Crystal structure of a double-stranded DNA containing a cisplatin interstrand cross-link at 1.63 A resolution: hydration at the platinated site.
cis-diamminedichloroplatinum (II) (cisplatin) is a powerful anti-tumor drug whose target is cellular DNA. In the reaction between DNA and cisplatin, covalent intrastrand and interstrand cross-links (ICL) are formed. Two solution structures of the ICL have been published recently. In both models the double-helix is bent and unwound but with significantly different angle values. We solved the crystal structure at 100K of a double-stranded DNA decamer containing a single cisplatin ICL, using the anomalous scattering (MAD) of platinum as a unique source of phase information. We found 47 degrees for double-helix bending and 70 degrees for unwinding in agreement with previous electrophoretic assays. The crystals are stabilized by intermolecular contacts involving two cytosines extruded from the double-helix, one of which makes a triplet with a terminal G.C pair. The platinum coordination is nearly square and the platinum residue is embedded into a cage of nine water molecules linked to the cross-linked guanines, to the two amine groups, and to the phosphodiester backbone through other water molecules. This water molecule organization is discussed in relation with the chemical stability of the ICL.
Base Pairing↗
Integrated transcriptome analysis of the cellular mechanisms associated with Ha-ras-dependent malignant transformation of the human breast epithelial MCF7 cell line.
To understand the cellular mechanisms of malignant transformation induced by constitutive activation of the ras oncogene (Ha-ras), we used a subtractive hybridization method (VGID) together with an integrative analytical procedure based upon literature databases in the form of extensive interaction graphs. We found 166 over- and under-expressed genes which, in the human MCF7-ras breast epithelial cell line, are involved in the different aspects of tumoral transformation such as defined signaling pathways, cellular growth, protection against apoptosis, extracellular matrix and cytoskeleton remodeling. Integrative analysis led to the construction of a physiological model defining cross-talk and signaling pathway alterations which explicitly suggested mechanisms directly involved in tumor progression. The model further suggested points and means of intervention which could induce cell death in Ha-ras-transformed cells specifically. These hypotheses were directly tested in vitro and found to be largely correct, hence indicating that these new analytical and technological approaches allow the discovery of pathology-associated cellular mechanisms and physiologically defined targets leading to phenotype-specific pharmacological interventions.
Algorithms↗
Chapter 20. The neurosurgeon's responsibility in "whiplash" injuries.
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Cerebellar Neoplasms↗
Expression of cholinesterase genes in human oocytes revealed by in-situ hybridization.
Transcriptional activity of the human cholinesterase genes was examined in developing oocytes from mature ovaries by in-situ hybridization combined with biochemical acetylcholine hydrolysis measurements. High levels of cholinesterase mRNA could be detected in oocytes from primordial, pre-antral and antral follicles but not in atretic follicles, with transient enhancement at the pre-antral stage. Biochemical analysis of enzymatic activity identified the ovarian enzyme as 'true' acetylcholinesterase by its sensitivity to selective inhibitors. Our findings suggest that cholinergic responses may function in human oocytes independently of the surrounding follicular cells, and the pronounced synthesis of cholinesterase transcripts in oocytes suggests that the cholinesterase genes in humans are particularly good candidates for the formation and re-insertion of inheritable processed cholinesterase genes.
Acetylcholinesterase↗
Quantitative measurement of the good and normal ranges in muscle testing.
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Humans↗
Detecting sincerity of effort: a summary of methods and approaches.
Despite the widespread use of methods that are supposed to detect the sincerity of patients' efforts in clinical assessment, little has been written summarizing the literature that addresses the reliability and validity of measurements obtained with these methods. The purpose of this article is to review the literature on the reliability and validity of scores for Waddell's nonorganic signs, descriptions of pain behavior and symptom magnification, coefficients of variation, correlations between musculoskeletal evaluation and function, grip measurements, and the relationship between heart rate and pain intensity. The authors of the articles reviewed conclude that none of these methods have been examined adequately. Some of these methods, such as Waddell's nonorganic signs, were not developed for the purpose of detecting sincerity of effort. Clinicians are encouraged to critically read the literature addressing these methods. With further research, some of the discussed methods may prove useful. Until such research is reported in the peer-reviewed literature, however, clinicians should avoid basing evaluation of sincerity of effort on these tests. Therapists are encouraged, instead, to use a biobehavioral approach to better understand and address the complex factors underlying delayed recovery.
Disability Evaluation↗
Schizophrenics' role in diagnosis.
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Autistic Disorder↗
Pharmacodynamic dose-response and safety study of cisatracurium (51W89) in adult surgical patients during N2O-O2-opioid anesthesia.
After administration of doses ranging from 0.025 to 0.25 mg/kg, the neuromuscular blocking effect of cisatracurium was assessed in 119 adult surgical patients receiving N2O-opioid-midazolam-thiopental anesthesia. The calculated 95% effective dose (ED95) for inhibition of adductor pollicis twitch evoked at 0.1 Hz was 0.053 mg/kg. With 0.10 mg/kg injected over 5-10 and 20-30 s, median onset times (range) were 5.8 (3.0-7.7) and 4.8 (1.2-10.2) min, respectively, and median times to 5% and 95% recovery (range) were 27 (19-46) and 48 (25-68) min, respectively. For doses of 0.10, 0.20, and 0.25 mg/kg, median 5%-95% and 25%-75% recovery indexes ranged from 48 to 90 min and 8 to 9 min, respectively. After administration of neostigmine (0.06 mg/kg) at 10%-15% or 16%-30% recovery, the median times to 95% recovery (range) were 6 (2-22) and 4 (2-5) min, respectively. There were no changes in heart rate, blood pressure, or plasma histamine concentrations during the first 5 min after administration of cisatracurium at doses up to 5 x ED95 injected over 5-10 s. No cutaneous flushing or bronchospasm was noted. In summary, cisatracurium is a potent neuromuscular blocking drug with an intermediate duration of action, characterized by excellent cardiovascular stability, with no apparent histamine release.
Adolescent↗