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N Valentin

Publications and source records attributed to N Valentin.

At least 19 recordsLinked to original sources
PubMed2001

A point mutation in the cysteine-rich domain of glycoprotein (GP) IIIa results in the expression of a GPIIb-IIIa (alphaIIbbeta3) integrin receptor locked in a high-affinity state and a Glanzmann thrombasthenia-like phenotype.

This article reports a Glanzmann thrombasthenia (GT) patient, N.M., with a point mutation in the third cysteine-rich repeat of beta3-integrin or platelet glycoprotein (GP) IIIa, leading to the expression of a constitutively activated fibrinogen receptor. The diagnosis of GT was based on a severely reduced platelet-aggregation response to a series of agonists and approximately 20% of surface-expressed GPIIb-IIIa. The patient's GPIIb-IIIa constitutively expressed epitopes recognized by antibodies to ligand-induced binding sites (LIBS) and also spontaneously bound the fibrinogen-mimetic antibody, PAC-1. Furthermore, significant amounts of bound fibrinogen were detected on his platelets ex vivo. No signs of platelet activation were observed on sections of unstimulated platelets from N.M. by electron microscopy. Immunogold labeling highlighted the presence of surface-bound fibrinogen but revealed platelet heterogeneity with regard to the surface density. When the patient's platelets were stimulated by thrombin-receptor activating peptide, amounts of surface-expressed GPIIb-IIIa increased and the aggregation response improved, although it failed to normalize. Platelets from N.M. were able to adhere and spread on immobilized fibrinogen. Sequence analysis of genomic DNA from N.M. revealed a homozygous g1776T>C mutation in GPIIIa, leading to a Cys560Arg amino acid substitution. A stable Chinese hamster ovary (CHO) cell line was prepared expressing surface GPIIb-Arg560IIIa. Like platelets from the patient, GPIIb-Arg560IIIa-transfected CHO cells constitutively bound LIBS antibodies and PAC-1. They also showed an enhanced ability to adhere on surface-bound fibrinogen. Overall, these data demonstrate that a gain-of-function mutation can still be associated with a thrombasthenic phenotype even though platelets show spontaneous fibrinogen binding.

Adult↗
PubMed1998

Analgesic efficacy and safety of preoperative versus postoperative ketorolac in paediatric tonsillectomy.

BACKGROUND: Tonsillectomy is a common procedure in childhood resulting in significant morbidity due to pain. The aim of this study was to evaluate the analgesic efficacy and safety of a single dose of ketorolac i.v. given before or after tonsillectomy, compared to placebo. METHODS: A randomized, double-blind, placebo-controlled study was performed in 60 children, 5 to 15 years of age, admitted for tonsillectomy. Patients were allocated to receive ketorolac 1 mg.kg-1 i.v. or placebo. Postoperative pain was assessed by self-report 1.5, 3, 5, and 24 h after surgery. RESULTS: Pain scores were significantly lower for both ketorolac groups compared to the placebo group 1.5, 3, and 5 h after surgery (P = 0.05). Pain scores were lowest in the preoperative ketorolac group 1.5 to 5 h after surgery, and significantly fewer children in this group had fentanyl 0 to 1.5 hr after surgery. But no significant differences were found between pain scores of the preoperative and postoperative ketorolac groups in the first 24 h after surgery. Acetaminophen consumption during the first 5 h after surgery was significantly less in patients receiving ketorolac (P < 0.05). Patients in the preoperative ketorolac group had a significantly lower incidence of postoperative vomiting (P < 0.05). There were no significant differences in the incidence of postoperative bleeding between groups. Three children in the preoperative, 5 children in the postoperative ketorolac group and 5 children in the placebo group experienced postoperative haemorrhage. CONCLUSION: This study indicates that a single dose of ketorolac 1 mg.kg-1 i.v. administered either before or immediately after surgery improves postoperative analgesia in children after tonsillectomy without evidence of increased incidence of bleeding.

Acetaminophen↗
PubMed1996

[Treatment of severe cancer pain via spinal catheters].

Twenty-seven patients with pain from non-curable cancer, who did not respond to systemic pain treatment with opioids and coanalgesics without the occurrence of unacceptable side effects, were treated with intrathecal infusions. Two patients were treated satisfactorily with morphine alone, while the remainder were given a mixture of morphine and bupivacaine. Complete or good pain relief was reported by 23 patients and some relief by three patients. The poorest results were obtained in the patients who died within the first week of intrathecal treatment. Post-spinal headache occurred in five patients and temporary paraesthesia or motor deficits in five. No serious complications were recorded. The treatment of severe cancer pain by intrathecal infusion of morphine and bupivacaine seems to be a promising method. As the adjustment of doses takes some days, and as the main complication, post-spinal headache, occurs early in the course, the method is most suitable for use in patients expected to survive for at least a couple of weeks.

Adult↗
PubMed1996

Ketamine anaesthesia for electrocochleography in children. Are psychic side effects really rare?

Retrospectively, we have studied the occurrence of psychic side effects in 121 children (median age 2.25 years) who have had ketamine anaesthesia for electrocochleography. For comparison, the same questionnaire was given to 66 children who had had ketamine for the surgery of squints. Early signs of psychic disturbance ( < 3 days) were equally frequent in the two groups, whereas late ( > 3 days) nightmare was most common in the patients undergoing cochleography (17% vs 5%). In several cases, signs of nightmare were reported by the parents to have lasted for months or even years. There was a significant (p = 0.00019) correlation between the occurrence of nightmare and the degree of hearing impairment. The frequency of late nightmare reported in the cochleography patients is unacceptably high, but as numerous possibilities of bias exist further investigations are necessary before conclusions can be safely drawn.

Anesthetics, Local↗
PubMed1995

Involvement of the cysteine-rich domain of glycoprotein IIIa in the expression of the human platelet alloantigen, PlA1: evidence for heterogeneity in the humoral response.

To assess the potential contribution of the cysteine-rich domain of human platelet glycoprotein (GP) IIIa to the structure of the PlA1 epitope, we used site-directed mutagenesis to substitute alanines for cysteines at key positions potentially involved in PlA1 alloantigen formation. One of these GPIIIa isoforms in which alanine replaced Cys435 reacted normally with a series of well-characterized murine MoAbs directed against the 250 amino-terminal residues of GPIIIa, whereas binding of MoAbs specific for residues 348-692 was diminished or lost. Interestingly, of eight PlA1-specific antibodies tested, two recognized Ala435GPIIIa, two did not, and four bound to it less well than to wild-type (WT) GPIIIa. However, disruption of disulfide bonds located at or near the N-terminus of GPIIIa abolished the binding of all the anti-PlA1 alloantibodies tested. These findings provide evidence that the humoral response to the PlA1 antigen is (1) heterogenous, ie, the binding site on GPIIIa for human anti-PlA1 antibodies differs from one individual to another and (2) complex--although some anti-PlA1 alloantibodies bind to an epitope comprised solely of the amino-terminus of GPIIIa, others combine most efficiently with a more complex determinant that involves the cysteine-rich domain of GPIIIa. These findings may have implications for diagnostic and therapeutic use of synthetic or recombinant PlA1 mimetics.

Alleles↗
PubMed1994

Susceptibility to alloimmunization to platelet HPA-1a antigen involves TAP1 polymorphism.

The alloimmunization against platelet HPA-1a antigen in mothers of thrombocytopenic neonates is strongly associated with HLA class II structures (DR3 and DR13) and especially with HLA-DR52a antigen (98% of the cases reported here). Because new genes have recently been mapped within the MHC class II region, we typed TAP1 and TAP2 gene polymorphisms by ARMS-PCR in order to characterize more effectively MHC genes involved in this alloimmunization. Our results showed that TAP1*0102 allele was significantly associated with NAIT only in the population of HLA-DR 13-DR52a-immunized women (50%) versus HLA-DR 13-DR52a controls (20%) (p < 0.05), and not in HLA-DR3-DR52a-immunized women versus HLA-DR3-DR52a controls. There is no linkage disequilibrium between TAP1*0102 and DRB1*13 alleles (delta = -0.0063) that could account for this result. The higher frequency of TAP1*0102 allele among HLA-DR 13-DR52a-immunized women suggests that HPA-1a antigen presentation and recognition may be influenced by nonclassic HLA class II gene polymorphisms, or that other linked but yet unknown genes could interfere.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Effect of nitrous oxide and volatile anaesthetics on platelet function in man.

Twelve otherwise healthy male volunteers scheduled for arthroscopy of the knee were studied. The influence in vivo of nitrous oxide (N2O) per se and the addition of a halogenated volatile anaesthetic (halothane or isoflurane) on ADP-induced platelet aggregation and release of beta-thromboglobulin into plasma was evaluated. All measurements were made before surgery. We found that N2O increased platelet aggregation. Adding a halogenated anaesthetic reversed the relative hyperaggregation induced by N2O. The concentrations in plasma of the platelet release product beta thromboglobulin were not influenced by the anaesthetics.

Adult↗
PubMed1994

Human platelet alloantigens.

The past 20 years have witnessed a revolution in our understanding of platelet alloimmunity, both in terms of basic findings and clinical applications. This review highlights recent molecular biological studies that have impacted our understanding of the structural basis for the formation of human platelet alloantigenic epitopes, and shows how these findings have improved methods for their detection and genotypic analysis. Finally, implications for dissecting the way in which the immune system both recognizes and responds to platelet alloantigens are discussed.

Antigens, Human Platelet↗
PubMed1993

[Buprenorphine for postoperative analgesia after total hip alloplasty].

Three different post-operative pain relief schedules were investigated in a double blind study after total hip replacement. Group BS received a priming dose of buprenorphine i.m. at the time of wound closure and continued with sublingual buprenorphine every eight hours. Supplementary doses of buprenorphine i.m. could be demanded. Group B and M received a priming dose of buprenorphine and morphine respectively, and continued with sublingual placebo eight hourly. Supplementary doses of buprenorphine could be demanded by patients in Group B and supplementary doses of morphine by patients in Group M. On one occasion VAS scorings of groups BS and B were statistically significantly lower than group M, and on another occasion VAS scorings of group BS were statistically significantly lower than the other two groups. Furthermore, the number of on demand supplementary doses was statistically significantly higher in group M. It is concluded that buprenorphine administered at regular intervals as well as on demand provided better postoperative analgesia than morphine at present dose levels. In this context, only moderate advantages were obtained by administering buprenorphine at regular intervals.

Adult↗
PubMed1993

Lack of binding of peptides carrying the human platelet antigen 1 (HPA-1) dimorphism to purified HLA-DRw52a molecules.

The strong association between anti-HPA-1a alloimmunization and DR3, DRw52a phenotype in HPA-1b homozygous women suggests that these class II molecules play a crucial role in the immune response against HPA-1a. The diallelic system HPA-1 results in a single amino acid polymorphism at the residue 33 of the glycoprotein IIIa. So, we tested the binding of peptides from the 25-42 region of the GPIIIa to purified HLA-DR3 and -DRw52a molecules, using a solid phase assay and a liquid phase peptide binding assay. No binding was demonstrated, indicating that either the crucial region for binding to class II molecules is not the 25-42 region, or that other events only occurring "in vivo" are required for binding. These results may also suggest an indirect role of the residue 33 for T-cell stimulation.

Amino Acid Sequence↗
PubMed1993

Glycopyrrolate vs. atropine during anaesthesia for laryngoscopy and bronchoscopy.

As glycopyrrolate has been reported superior to atropine with respect to reduction of salivation, stability of cardiac rate and rhythm, and recovery, a comparison of these properties of the two drugs and placebo was made in 45 patients undergoing direct laryngoscopy and 45 patients undergoing bronchoscopy, in most cases followed by mediastinoscopy. When given i.m. 30 min before anesthesia (midazolam, alfentanil, thiopentone, and suxamethonium), the two test drugs were found to be equally potent regarding the antisialogogic effect. The same increase in heart rate after the test drugs was seen before induction, and during anaesthesia heart rate rose to the same level in the placebo group as the test groups. During anaesthesia, blood pressure was lowest in the atropine group. No differences could be demonstrated with respect to cardiac arrhythmias, possibly due to the small size of the material. The present study gives no reason for preferring either drug, and only the efficacy of both test drugs in controlling airway secretions provides an argument for using any anticholinergic drug when laryngoscopy or bronchoscopy is performed under the conditions of the present study.

Adult↗
PubMed1992

Total intravenous anaesthesia for direct laryngoscopy: propofol infusion compared to thiopentone combined with midazolam and methohexitone infusion.

Total intravenous anaesthesia for direct laryngoscopy was investigated in 40 patients, randomized into four groups of 10 patients each. First, propofol infusion was compared to thiopentone combined with midazolam. Next, a comparison of propofol infusion with methohexitone infusion was undertaken. The propofol group showed significantly lower peroperative blood pressure compared to the thiopentone/midazolam group. The second propofol group required significantly less alfentanil to stabilize the blood pressure, compared to the methohexitone group. Completeness of recovery, assessed by means of a coin counting test, was faster in the propofol group compared to the thiopentone/midazolam group, while no difference could be demonstrated between the second propofol group and the methohexitone group. It is concluded that propofol seems to be superior to both thiopentone/midazolam and methohexitone with respect to the stability of peroperative blood pressure. Concerning recovery, propofol is superior to thiopentone/midazolam, but offers no advantage over methohexitone.

Adult↗