Monitoring of the responsiveness to noxious stimuli during anaesthesia with propofol and remifentanil by using RIII reflex threshold and bispectral index.

BACKGROUND: Movement responses are an important indicator of noxious perception in the unconscious state. To allow for a continual monitoring of the responsiveness to noxious stimuli during general anaesthesia, surrogate parameters are needed. Here we compare the performance of the bispectral index (BIS) and the RIII threshold in predicting reactions to noxious stimuli during anaesthesia with propofol and remifentanil. METHODS: Twenty male volunteers were included. The first 10 subjects received constant concentrations of propofol while remifentanil concentrations were increased stepwise. The other 10 subjects each received high propofol concentrations combined with different low remifentanil concentrations and also low propofol concentrations combined with different high remifentanil concentrations. In all subjects, the reactions to an 80 mA 30 s tetanic stimulus were tested every 5 min. BIS and RIII threshold were recorded continually in all subjects. RESULTS: Nineteen subjects completed the study. The population prediction probability for reactions to the noxious stimuli amounted to 0.86 for the BIS and to 0.84 for the RIII threshold in the first 10 subjects (P>0.05, PKDMACRO). In the other nine subjects, the prediction probabilities amounted to 0.64 for the BIS and to 0.77 for the RIII threshold (P<0.05, PKDMACRO). All population prediction probability values differed significantly from 0.5 (P<0.01, PKDMACRO). CONCLUSIONS: RIII threshold and BIS are both influenced dose-dependently by remifentanil at those concentrations that suppress reactions to noxious stimuli. The susceptibility of the parameters to remifentanil concentration seems to be of a similar quality. Under different ratios of propofol and remifentanil concentrations, the RIII threshold correlates with non-responsiveness better than the BIS.

Comparison of the nociceptive flexion reflex threshold and the bispectral index as monitors of movement responses to noxious stimuli under propofol mono-anaesthesia.

BACKGROUND: Prediction of movement responses to noxious stimuli during anaesthesia is of clinical importance. Susceptibility of a parameter of immobility to both hypnotic and analgesic influences could pose an advantage. Here, nociceptive reflexes might be useful, but data regarding the suppression by hypnotic substances are scarce. Therefore, we compared the prediction of movement responses by the RIII reflex threshold and the bispectral index (BIS) during propofol mono-anaesthesia. METHODS: Fifteen male volunteers were included. Propofol effect compartment concentration was increased every 15 min in steps of 1 microg ml(-1) (max 7 microg ml(-1)). Every 5 min, the reactions to trapezius squeezes and 30 s tetanic stimulations (80 mA) of the right ulnar nerve were tested. The RIII reflex threshold was estimated continuously using an automated threshold tracking system that analyses the nociceptive RIII response at the left biceps femoris muscle to stimulation of the left sural nerve. RESULTS: Twelve subjects completed the study. RIII threshold values were normalized by subtraction of the first threshold that was estimated after the subject's loss of consciousness. The population prediction probability P(K) amounted to 0.84 for the RIII threshold and to 0.86 for the BIS (difference not significant). CONCLUSIONS: Movement responses to noxious stimuli under propofol can be predicted by the RIII threshold with a comparable accuracy as the BIS. Therefore, the RIII threshold seems to be influenced by hypnotic effects. Since susceptibility of the RIII threshold to analgesic influences is well established, an advantage for the RIII threshold in the prediction of motor responses could be expected when analgesic substances are used in addition to propofol.

Large deletions 5' to the ETO breakpoint are recurrent events in patients with t(8;21) acute myeloid leukemia.

Recurrent chromosomal rearrangements are observed in many leukemia subtypes. Recently, it has been shown that several of these translocations/inversions were associated with the loss of sequences located in the vicinity of the chromosomal breakpoints. So far, such deletions have not been described for the t(8;21) translocation. We have analyzed a series of 65 patients with t(8;21) using several probes specific for the ETO and AML1 regions. We have found six patients (9%) with deletion of the region 5' to ETO. In all six patients, the deletion encompassed at least 260 kb, and was even larger in two patients (up to 2 Mb). A similar analysis of the 21q22 region did not reveal any deletion of the 3'AML1 region. In conclusion, cytogenetically undetectable small deletions located immediately 5' to the ETO breakpoint were found to accompany the t(8;21) translocation in a significant percentage of cases. The clinical significance, if any, of these deletions remains to be determined.

Fluorescence in situ hybridization detection of two telomeres on the short arm of a derived chromosome 16 in an infant with thrombocytopenia.

We report a case of severe thrombocytopenia with an abnormal bone marrow karyotype described by G-banding analysis as t(16;21)(p?13;q11). Using fluorescence in situ hybridization (FISH) analysis with whole chromosome paints, the chromosome rearrangement was shown to be more complex, with the additional cryptic involvement of the long arm of chromosome 3. The chromosome rearrangement involved the breakpoints 3q26, 16p13.3, and 21q11; this rearrangement has not been previously described. The size of genomic material translocated from the chromosome 16 homologue was too small to be detected by chromosome paint. A 16p-specific telomeric probe was hybridized to locate the translocated 16p material. The 16p telomeric unique sequence DNA was retained on the der(16) chromosome, indicating a more distal breakpoint. This study demonstrates that telomeric translocations can occur that would be undetected by telomeric-specific FISH probes.

Lymphadenopathy, splenomegaly, and altered immunoglobulin production in BCL3 transgenic mice.

The candidate proto-oncogene BCL3 was isolated through its involvement in the t(14;19) found in chronic lymphocytic leukemia and other B-cell neoplasms. As a member of the I kappaB family, BCL3 plays a role in the immune response by interactions with the NF-kappaB family of transcription factors. In order to study the role of BCL3 overexpression in lymphoid malignancies, we generated five lines of E mu-BCL3 transgenic mice. Transgenic animals develop normally but show splenomegaly and an accumulation of mature B cells in lymph nodes, bone marrow and peritoneal cavity. A hyperresponsive immune system is suggested by the follicular hyperplasia and plasmacytosis in lymph nodes of unimmunized animals, increased incidence of antibodies to self-antigens, and a heightened response to cross-linking of surface IgM. Statistically significant decreases in serum IgM and IgG3, but an increase in IgG1 and IgA were also observed. No lymphoid neoplasms have been identified in transgenic animals. The expansion of B cells in vivo is consistent with the overexpression of BCL3 as being one step in the multi-step process of leukemogenesis. The phenotype also suggests that BCL3 plays a part in B cell proliferation and isotype switching.

CpG-rich sequences close to the site of duplication within the human IGH constant region.

Human immunoglobulin heavy chains are encoded by a highly complex locus, IGH, which encompasses many transcriptional units, including nine alternative constant region genes. Much of the constant region gene cluster was duplicated during hominoid evolution. In rodents, IGH is known to be regulated by multiple elements, including several enhancers 3' of the alpha chain-encoding A constant region gene, CA, the last transcribed region. Sequences downstream of the two human CA genes, possibly containing homologous enhancer elements, have not yet been reported. By long-range mapping of genomic DNA, a cluster of unmethylated rare restriction sites, representing a potential CpG island, was previously reported downstream of each CA gene, close to the 3' end of the duplicated region. Such potential CpG islands are candidates for additional IGH regulatory elements. We isolated bacteriophage clones containing these clusters of methylation-sensitive restriction sites, which lie within short CpG-rich stretches. Some of these sites showed tissue-specific methylation. 3' of the unmethylated CpG-rich sequences, clones derived from the 5' (telomeric) copy of the duplicated region, contained, in order, endogenous retroviral sequences, a processed ELK1 pseudogene, and the pseudogene IGHGP. Comparison with the presumed 3' (centromeric) copy of the duplicated region showed that similarity was lost exactly at the end of the retroviral long terminal repeat sequences. These results imply that an endogenous retroviral integration was present immediately 3' of IGH in the common hominoid ancestor and suggest models for the duplication of the region.