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Biomedical subjects

L Bergeron

Publications and source records attributed to L Bergeron.

At least 19 recordsLinked to original sources

Intrathecal fentanyl does not modify the duration of spinal procaine block.

PURPOSE: To document the clinical characteristics of spinal procaine with or without the addition of fentanyl in light of the failure rate observed previously with procaine 10%. METHODS: In a randomized, prospective, double-blind study, 52 patients received spinal anesthesia with 100 mg procaine and either saline 0.9% (0.4 ml) (CONTROL group) or 20 microg fentanyl (0.4 ml) (FENTANYL group). Sensory anesthesia to needle prick was evaluated each minute for ten minutes, every three minutes for 33 minutes and every five minutes until regression to T10. Motor block was assessed with the Bromage scale. Patients were questioned by telephone for pain suggesting transient radicular irritation (TRI) 48 hr later. RESULTS: Mean time to reach highest sensory level, maximum number of segments blocked and mean time for regression of the sensory level to T10 showed no difference. Time to recuperate to full flexion of knees and feet (Bromage 4) showed no difference. Nine patients had nausea (five in CONTROL group and four in FENTANYL group) and nine had pruritus (three in CONTROL group and six in FENTANYL group). No patient reported pain suggesting TRI. CONCLUSION: Spinal procaine is appropriate for short-duration surgery. Fentanyl does not change the characteristics of the block or the incidence of side effects associated with spinal procaine.

Adolescent↗

Spinal anesthesia: a comparison of procaine and lidocaine.

PURPOSE: To compare spinal procaine to spinal lidocaine with regard to their main clinical characteristics and incidence of transient radicular irritation (TRI). METHODS: In this randomized, double-blind, prospective study, patients (two groups, n=30 each) received either 100 mg of lidocaine 5% in 7.5% glucose (Group L) or 100 mg of procaine 10% diluted with 1 ml cerebrospinal fluid (Group P). After spinal anesthesia, segmental level of sensory block was assessed by pinprick. Blood pressure and the height of the block were noted each minute for the first ten minutes, then every three minutes for the next 35 min and finally every five minutes until regression of the block to L4. Motor blockade was evaluated using the Bromage scale. To evaluate the presence of TRI, each patient was questioned 48 hr after surgery. RESULTS: Time to highest sensory level and to maximum number of segments blocked showed no difference between groups. Mean time for sensory regression to T10 and for regression of the motor block were shorter in Group P. Eighty minutes following injection, sensory levels were lower in Group P. Five patients had inadequate surgical anesthesia in Group P and only one in Group L. No patient in Group P had TRI (95% CI 10-12%) while eight (27%) in Group L did (95% CI 12-46%). CONCLUSIONS: Procaine 10% was associated with a clinical failure rate of 14.2%. This characteristic must be balanced against an absence of TRI, which occurs more frequently with the use of lidocaine 5%.

Adult↗

Caspase-2 deficiency prevents programmed germ cell death resulting from cytokine insufficiency but not meiotic defects caused by loss of ataxia telangiectasia-mutated (Atm) gene function.

It is well established that programmed cell death claims up to two-thirds of the oocytes produced during gametogenesis in the developing fetal ovaries. However, the mechanisms underlying prenatal germ cell loss in females remain poorly understood. Herein we report that caspase-11 null female mice are born with a reduced number of oocyte-containing primordial follicles. This phenotype is likely due to failed cytokine processing known to occur in caspase-11 mutants since neonatal female mice lacking both interleukin (IL)-1alpha and IL-1beta also exhibit a reduced endowment of primordial follicles. In addition, germ cell death in wild-type fetal ovaries cultured ex vivo is suppressed by either cytokine, likely via ligand activation of type 1 IL-1 receptors expressed in fetal germ cells. Normal oocyte endowment can be restored in caspase-11 null female mice by simultaneous inactivation of the gene encoding the cell death executioner enzyme, caspase-2. However, caspase-2 deficiency cannot overcome gametogenic failure resulting from meiotic recombination defects in ataxia telangiectasia-mutated (Atm) null female mice. Thus, genetically distinct mechanisms exist for developmental deletion of oocytes via programmed cell death, one of which probably functions as a meiotic quality-control checkpoint that cannot be overridden.

Animals↗

Concentration-effect relationship of cisatracurium at three different dose levels in the anesthetized patient.

BACKGROUND: The linearity of cisatracurium elimination and its concentration-effect relation were determined as part of a traditional rich data study with three dose levels in patients receiving balanced anesthesia. METHODS: Forty-eight adults with American Society of Anesthesiologists status I-II were randomized to receive an intravenous bolus dose of 0.075, 0.15, or 0.30 mg/kg cisatracurium. Anesthesia was induced and maintained with nitrous oxide-oxygen, propofol, and fentanyl. The mechanical response of the adductor pollicis muscle was recorded. Arterial blood samples were collected over 8 h. Cisatracurium, laudanosine, and the monoquaternary alcohol concentrations were measured by high-performance liquid chromatography. To assess the relative contribution of the input function, a parametric (assuming elimination from both the central and peripheral compartments) and a nonparametric pharmacokinetic-pharmacodynamic model were both applied to data. RESULTS: Dose proportionality of the body disposition of cisatracurium and its two major metabolites at doses up to 0.30 mg/kg was confirmed. With the parametric approach, the effect compartment concentration at 50% block (EC50) significantly increased with the dose (136 vs. 157 vs. 209 ng/ml), whereas the effect compartment equilibration rate constant decreased (0.0675 vs. 0.0568 vs. 0.0478 min(-1)). A similar dose-dependent effect of the pharmacokinetic-pharmacodynamic relation was observed with the nonparametric approach, but the trend was 50% less pronounced. CONCLUSION: A dose-related change in pharmacokinetic-pharmacodynamic parameters was identified with both modeling approaches. A pharmacokinetic origin was ruled out, although no definite explanation of the underlying mechanism could be provided. These findings suggest that doses relevant to the anesthetic practice be used for estimation of EC50.

Adolescent↗

Correlates of mental disorders in the Quebec general population of 6 to 14-year olds.

Previous epidemiological studies of correlates of child and adolescent mental disorders in the general population have focused more on child/adolescent and socioeconomic/sociodemographic characteristics than on family characteristics. Moreover, there are no generally accepted methods to analyze and interpret correlates. The purpose of the Quebec Child Mental Health Survey in this regard was twofold: (1) to identify correlates of DSM-III-R internalizing and externalizing disorders according to informant (youth, parent, teacher), for three age groups (6-8, 9-11, and 12-14 years), including relevant family characteristics not considered in previous studies; and (2) to interpret the relative importance of risk indicators by ranking correlates according to strength and consistency of association across age groups. Logistic regression models suggest the inconsistency of correlates across informants. The ranking of correlates reveals that individual and family characteristics make a more important contribution than do socioeconomic characteristics, thereby supporting the relevance of proximal variables in the development of psychopathology.

Adolescent↗

The Dominic-R: a pictorial interview for 6- to 11-year-old children.

OBJECTIVE: To review the Dominic-R and the Terry questionnaires, respectively, for white and African-American children, both DSM-III-R-based, and more recent DSM-IV-based computerized versions. METHOD: Five papers describing the development, content, validation studies, and establishment of the diagnostic cutpoints of these instruments are reviewed. The instruments are pictorial, fully structured, and designed to assess mental disorders in children 6 to 11 years of age. Symptom descriptions complement the visual stimulus, providing better information-processing than visual or auditory stimuli alone. Cognitive immaturity of young children bars frequency, duration, and age-of-onset measurements, restricting correspondence with DSM criteria. DSM-IV (computerized versions) and DSM-III-R (paper versions) disorders being assessed include specific (simple) phobias, separation anxiety, generalized anxiety (overanxious), depression/dysthymia, attention-deficit hyperactivity, oppositional defiant, and conduct disorder. RESULTS: Test-retest reliability of symptoms and symptom scores and criterion validity against clinical judgment support the visual-auditory combination of stimuli to assess child mental health. CONCLUSION: Intended for clinical, epidemiological, and screening purposes, these instruments are short and simple. Although it only approximates DSM-III-R and DSM-IV criteria, the pictorial format permits young children to be reliable informants about their mental health.

Child↗

Spinal procaine with and without epinephrine and its relation to transient radicular irritation.

PURPOSE: To document the clinical characteristics of procaine with or without the addition of epinephrine. METHODS: In this randomized, prospective, double blind study, 62 patients received spinal anesthesia with 100 mg procaine and either 0.3 mg epinephrine (EPI group) or 0.3 ml NaCl 0.9% (SALINE group). Sensory anesthesia to needle prick was evaluated q 1 min for 10 min, q 3 min for 33 min and q 5 min until regression to L4. Motor block was assessed with the Bromage scale. Patients were questioned, by telephone, for transient radicular irritation (TRI) 48 hr later. RESULTS: Time to reach highest sensory level and number of segments blocked showed no difference. Mean time for regression of the sensory level to T10 was longer in EPI (83 +/- 23 vs 66 +/- 20 min, P < 0.01). Time to recuperate to full flexion of knees and feet (Bromage 4) was longer in EPI (126 +/- 37 vs 100 +/- 30 min, P < 0.01). Patients in EPI received more ephedrine. Eighteen patients had nausea (15 EPI/3 SALINE, P < 0.0015). One patient had TRI, incidence: 1.67%, 95% CI (< 1%-9%). CONCLUSION: Spinal procaine is appropriate for surgery of short duration. Epinephrine prolongs sensory and motor blocks by 25%. However, it is associated with a high incidence of nausea.

Adult↗

Quebec child mental health survey: prevalence of DSM-III-R mental health disorders.

The Quebec Child Mental Health Survey (QCMHS) was conducted in 1992 on a representative sample of 2400 children and adolescents aged 6 to 14 years from throughout Quebec. Prevalences of nine Axis-I DSM-III-R (American Psychiatric Association, 1987) mental health disorders were calculated based on each informant (for 6-11-year-olds: child, parent, and teacher; for 12-14-year-olds: child and parent). Informant parallelism allows the classification of results of the demographic variables associated with disorders in the logistic regression models. This strategy applies to group variables (correlates of disorders) whereas informant agreement applies to individual diagnoses. Informant parallelism implies that results for two informants or more are in the same direction and significant. In the QCMHS, informant parallelism exists for disruptive disorders, i.e. in two ADHD regression models (child and parent) higher rates among boys and young children, and in three oppositional/conduct disorders regression models (child, parent, and teacher) higher rates among boys. No informant parallelism is observed in the logistic regression models for internalizing disorders, i.e. the patterns of association of demographic variables with anxiety and depressive disorders vary across informants. Urban-rural residence does not emerge as a significant variable in any of the logistic regression models. The overall 6-month prevalences reach 19.9% according to the parent and 15.8% according to the child. The implications of the results for policy makers and clinicians are discussed.

Adolescent↗

Defects in regulation of apoptosis in caspase-2-deficient mice.

During embryonic development, a large number of cells die naturally to shape the new organism. Members of the caspase family of proteases are essential intracellular death effectors. Herein, we generated caspase-2-deficient mice to evaluate the requirement for this enzyme in various paradigms of apoptosis. Excess numbers of germ cells were endowed in ovaries of mutant mice and the oocytes were found to be resistant to cell death following exposure to chemotherapeutic drugs. Apoptosis mediated by granzyme B and perforin was defective in caspase-2-deficient B lymphoblasts. In contrast, cell death of motor neurons during development was accelerated in caspase-2-deficient mice. In addition, caspase-2-deficient sympathetic neurons underwent apoptosis more effectively than wild-type neurons when deprived of NGF. Thus, caspase-2 acts both as a positive and negative cell death effector, depending upon cell lineage and stage of development.

Amyotrophic Lateral Sclerosis↗

Sealing one's fate: control of cell death in neurons.

BCL-2 family members and caspases are essential components of the death machinery in neurons. Identification of Apaf-1 as the mammalian homologue of Caenorhabditis elegans ced-4 provided the final proof of the complete conservation of the C. elegans programmed cell death pathway in mammals. When neurons are deprived of trophic factors, a sequence of events is initiated, which includes a reduction in macromolecule synthesis, elevation of c-Jun and cyclin D1, and activation of BAX. The final episode of this sequence is the activation of caspases, which may mark the death commitment point at which neurons cannot be rescued by addition of trophic factors. In addition, recent evidence suggests that the components in the developmental programmed cell death pathway may play a critical role in neurodegenerative disorders.

Animals↗

Reliability of the Terry: a mental health cartoon-like screener for African-American children.

Test-retest reliability and internal consistency of the Terry, a cartoon-based child mental health screener developed for African-American children, were measured in 36 boys (age 5 1/2 to 13) in a test-retest design. Reliability of the diagnosis (0.70 < or = k < or = 0.75) was good for ADHD, ODD, CD, and OAD, and excellent for MDD and SAD. Because of low base-rate, no kappa value was calculated for SPh. Both test-retest agreement, and reliability of the symptom scale (0.75 < or = ICC < or = 0.80) were very good for all 7 diagnoses. Internal consistency according to symptom scale (0.78 < or = Cronbach alpha < or = 0.90), was moderate for OAD, good for SPh, MDD, SAD, CD, and ODD, and excellent for ADHD. The Terry is a culturally-sensitive questionnaire with good reliability.

Adolescent↗

Diagnostic Interview Schedule for Children (DISC-2.25) in Quebec: reliability findings in light of the MECA study.

OBJECTIVE: To examine the reliability of the French Diagnostic Interview Schedule for Children (DISC-2.25) in Quebec in light of other DISC-2 studies conducted in the National Institute of Mental Health's Methods for the Epidemiology of Child and Adolescent Mental Disorders Study. METHOD: Reliability was assessed for DSM-III-R disorders in a community sample comprising 260 parents of youths aged 6 to 14 years and 145 adolescents aged 12 to 14 years. The DISC was completed at home. The mean test-retest interval was 13.8 days for parents and 12.8 days for adolescents. RESULTS: Parents' reports: Internal consistency was acceptable for a majority of disorders. The kappa coefficients were in the fair or good ranges except for depressive disorders and were higher for children than for adolescents, and intraclass correlations were higher than kappa coefficients. Adolescents' reports: Internal consistency was acceptable or nearly acceptable for a majority of disorders. The kappa coefficients were in the fair range, and intraclass correlations were higher than kappa coefficients. The kappa coefficients were significantly higher for the test-retest interval of 7 to 14 days than for 14 to 21 days for adolescents' reports of anxious disorders and internalizing disorders. CONCLUSION: The French DISC-2.25 shows acceptable internal consistency and fair to good test-retest reliability. Across DISC-2 studies, test-retest reliability of the parents' reports improved for anxiety and depressive disorders. Among sources of variation, studies on attributes of questions would be meaningful.

Adolescent↗

Activation of caspase-2 in apoptosis.

Members of the CED-3/interleukin-1beta-converting enzyme (ICE) protease (caspase) family are synthesized as proforms, which are proteolytically cleaved and activated during apoptosis. We report here that caspase-2 (ICH-1/NEDD-2), a member of the ICE family, is activated during apoptosis by another ICE member, a caspase-3 (CPP32)-like protease(s). When cells are induced to undergo apoptosis, endogenous caspase-2 is first cleaved into three fragments of 32-33 kDa and 14 kDa, which are then further processed into 18- and 12-kDa active subunits. Up to 50 microM N-acetyl-Asp-Glu-Val-Asp-aldehyde (DEVD-CHO), a caspase-3-preferred peptide inhibitor, inhibits caspase-2 activation and DNA fragmentation in vivo, but does not prevent loss of mitochondrial function, while higher concentrations of DEVD-CHO (>50 microM) inhibit both. In comparison, although the activity of caspase-3 is very sensitive to the inhibition of DEVD-CHO (<50 nM), inhibition of caspase-3 activation as marked by processing of the proform requires more than 100 microM DEVD-CHO. Our results suggest that the first cleavage of caspase-2 is accomplished by a caspase-3-like activity, and other ICE-like proteases less sensitive to DEVD-CHO may be responsible for activation of caspase-3 and loss of mitochondrial function.

Apoptosis↗

Characterization of the avian Ich-1 cDNA and expression of Ich-1L mRNA in the hen ovary.

We have sequenced the chicken interleukin-1beta-converting enzyme (ICE) and ced-3 homolog (Ich-1) cDNA, and evaluated Ich-1 mRNA expression in the hen ovary during follicle development. While two alternatively spliced forms of Ich-1, Ich-1L and Ich-1S, were amplified by PCR from an embryonic chicken cDNA library, only the Ich-1L form was found to be expressed in adult ovarian granulosa and theca tissues. The deduced amino acid (aa) sequence of ICH-1L is 70.8% identical to human ICH-1L and contains the conserved QACRG peptide active catalytic sequence characteristic of many ICE-related family of cysteine proteases.

Amino Acid Sequence↗

Reliability of the Dominic-R: a young child mental health questionnaire combining visual and auditory stimuli.

Reliability of the Dominic-R, a questionnaire combining visual and auditory stimuli, was tested in 340 community children aged 6 to 11 years. Test-retest reliability of symptoms of, and symptom scores of, DSM-III-R disorders including simple phobias, separation anxiety disorder, overanxious disorder, depression/dysthymia, attention deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder was assessed. Most symptoms yielded kappas greater than .40, and ICCs ranged from .74 to .81. In conclusion, reliability of the Dominic-R compares favourably with that of other child assessment questionnaires.

Auditory Perception↗

Specific cleavage of alpha-fodrin during Fas- and tumor necrosis factor-induced apoptosis is mediated by an interleukin-1beta-converting enzyme/Ced-3 protease distinct from the poly(ADP-ribose) polymerase protease.

Interleukin-1beta-converting enzyme (ICE)/Ced-3 proteases play a critical role in apoptosis. One well characterized substrate of these proteases is the DNA repair enzyme poly(ADP-ribose) polymerase. We report here that alpha-fodrin, an abundant membrane-associated cytoskeletal protein, is cleaved rapidly and specifically during Fas- and tumor necrosis factor-induced apoptosis; this cleavage is mediated by an ICE/Ced-3 protease distinct from the poly(ADP-ribose) polymerase protease. Studies in cells treated with these apoptotic stimuli reveal that both fodrin and poly(ADP-ribose) polymerase proteolysis are inhibited by acetyl-Tyr-Val-Ala-Asp chloromethyl ketone and CrmA, specific inhibitors of ICE/Ced-3 proteases. However, fodrin proteolysis can be distinguished from poly(ADP-ribose) polymerase proteolysis by its relative insensitivity to acetyl-Asp-Glu-Val-Asp aldehyde (DEVD-CHO), a selective inhibitor of a subset of ICE/Ced-3 proteases that includes CPP32. DEVD-CHO protects cells from Fas-induced apoptosis but does not prevent fodrin proteolysis, indicating that cleavage of this protein can be uncoupled from apoptotic cell death. Moreover, purified fodrin is cleaved in vitro by CPP32 (but not by ICE) into fragments of the same size observed in vivo during apoptosis. These findings suggest that fodrin proteolysis in vivo may reflect the activity of multiple ICE/Ced-3 proteases whose partial sensitivity to DEVD-CHO reflects a limited contribution from CPP32, or an ICE/Ced-3 protease less sensitive than CPP32 to DEVD-CHO inhibition.

Apoptosis↗

Activation of an interleukin 1 converting enzyme-dependent apoptosis pathway by granzyme B.

Cytotoxic T lymphocytes (CTL) can induce apoptosis through a granzyme B-based killing mechanism. Here we show that in cells undergoing apoptosis by granzyme B, both p45 pro-interleukin 1 beta converting enzyme (ICE) and pro-CPP32 are processed. Using ICE deficient (ICE -/-) mice, embryonic fibroblasts exhibit high levels of resistance to apoptosis by granzyme B or granzyme 3, while B lymphoblasts are granzyme B-resistant, thus identifying an ICE-dependent apoptotic pathway that is activated by CTL granzymes. In contrast, an alternative ICE-independent pathway must also be activated as ICE -/- thymocytes remain susceptible to apoptosis by both granzymes. In ICE -/- B cells or HeLa cells transfected with mutant inactive ICE or Ich-1S that exhibit resistance to granzyme B, CPP32 is processed to p17 and poly(ADP-ribose) polymerase is cleaved indicating that this protease although activated was not associated with an apoptotic nuclear phenotype. Using the peptide inhibitor Ac-DEVD-CHO, apoptosis as well as p45 ICE hydrolysis are suppressed in HeLa cells, suggesting that a CPP32-like protease is upstream of ICE. In contrast, p34cdc2 kinase, which is required for granzyme B-induced apoptosis, remains inactive in ICE -/- B cells indicating it is downstream of ICE. We conclude that granzyme B activates an ICE-dependent cell death pathway in some cell types and requires a CPP32-like Ac-DEVD-CHO inhibitable protease acting upstream to initiate apoptosis.

Animals↗