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PubMed1991

Further characterization of the loop structure of platelet glycoprotein IIIa: partial mapping of functionally significant glycoprotein IIIa epitopes.

Glycoprotein (GP) IIb-IIIa serves as the platelet fibrinogen receptor. Studies of the tertiary structure of GPIIIa have shown that the protein has a large loop structure of at least 325 amino acids in length. To further characterize this loop structure, intact platelets were digested with alpha-chymotrypsin. Digestion products were examined using the anti-GPIIIa monoclonal antibodies (MoAbs) AP3, D3GP3, and C5GP3, as well as the human alloantibody, anti-PLA1. AP3 recognized GPIIIa digestion products of 109, 95, and 68 Kd. D3GP3 and C5GP3 recognized an additional band of 51 Kd. Time course digestions demonstrated that the 51-Kd fragment was generated by proteolysis of the 68-Kd peptide. Sequence analysis of the reduced 51-Kd peptide showed that this fragment began at amino acid 422. The nonreduced 51-Kd peptide was reactive with antibodies directed against the first 13 amino acids of GPIIIa, demonstrating the presence of a covalently attached N-terminal peptide. These data suggest that: (1) the minimum length of the loop structure is at least 384 amino acids; (2) the AP3 epitope is formed at least in part by a determinant contained within residues 348 to 421; and (3) the D3GP3 and C5GP3 epitopes are contained within amino acids 422 to 692 of GPIIIa, a region that may be flexible and involved in conformational changes that occur after ligand binding.

Amino Acid Sequence↗
PubMed1991

Neutralizing determinants of canine herpesvirus as defined by monoclonal antibodies.

Monoclonal antibodies (MoAbs) against canine herpesvirus (CHV) were produced to identify the immunogenic proteins of the virus carrying neutralizing determinants. A panel of 24 MoAbs showing neutralizing activities was obtained and tentatively classified into 3 different groups based on their reactivity patterns in immunoblotting analysis. Group I consisting of 10 clones was specific for 145/112 kDa; Group II of 9 clones, for 80 kDa; and Group III of 5 clones, for 41 kDa glycoproteins (gps). Complement-requirement for neutralizing activities of the MoAbs suggests that gp 145/112 and gp 80 elicit mainly complement-requiring and -enhanced neutralizing antibodies, while gp 41 elicits complement-independent ones. In addition, these MoAbs were used in ELISA additivity tests for functional and topographical mapping of epitopes in each of the CHV gp. The results indicated that antigenic reactivities of gp 145/112 and gp 80 were, respectively, localized on at least 5 and 7 overlapping epitopes. On the other hand, 4 epitopes were identified on gp 41.

Animals↗
PubMed1992

Comparison and fine mapping of both high and low neutralizing monoclonal antibodies against the principal neutralization domain of HIV-1.

Monoclonal antibodies raised against viral lysate of HIV-1 (strain LAV-1) and against recombinant gp 160 of HIV-1 (strain HTLV IIIB) which neutralized HIV-1 in a type specific manner were mapped with the aid of peptides (Pepscan analysis). Each of these monoclonal antibodies bound to peptides located on the principal neutralizing domain (PND) of HIV-1. We found that the antigenic sites of the MAbs described in this paper are represented by linear peptides of at least 10 amino acids long. The affinity of the MAbs is high for these peptides and in the same order of magnitude as for native gp 160. The fine mapping of the epitopes may reflect structural features of the PND, for instance which amino acid side chains are exposed and which are buried in the protein. Furthermore the fine mapping of the epitopes explained the HIV type-specific neutralizing activity of the MAbs. Antibodies that bound to the tip of the loop (amino acids QRGPGRAF) have a higher neutralizing activity than antibodies that bound to amino acids towards the N-terminal side of the loop (amino acids KSIRI). Furthermore, MAbs that bound to virtually the same amino acids on the tip of the loop (amino acids IQRGPGRAF and RGPGRAFV) had different neutralizing activities due to different affinities for native gp 160. These data reveal that neutralizing activity not only is determined by the affinity of an antibody to the neutralizing site but also by its fine binding specificities to the V 3 loop of gp 120.

Amino Acid Sequence↗
PubMed2004

Assessment of tracheal intubating conditions in children using remifentanil and propofol without muscle relaxant.

BACKGROUND: Tracheal intubation in children can be achieved by deep inhalational anaesthesia or an intravenous anaesthetic and a muscle relaxant, suxamethonium being widely used despite several side-effects. Studies have shown that oral intubation can be facilitated safely and effectively in children after induction of anaesthesia with propofol and alfentanil without a muscle relaxant. Remifentanil is a new, ultra-short acting, selective mu-receptor agonist that is 20-30 times more potent than alfentanil. This clinical study was designed to assess whether combination of propofol and remifentanil could be used without a muscle relaxant to facilitate tracheal intubation in children. METHODS: Forty children (5-10 years) admitted for adenotonsillectomy were randomly allocated to one of two groups to receive remifentanil 2 microg.kg(-1) (Gp I) or remifentanil 3 microg.kg(-1) (Gp II) before the induction of anaesthesia with i.v. propofol 3 mg.kg(-1). No neuromuscular blocking agent was administered. Intubating conditions were assessed using a four-point scoring system based on ease of laryngoscopy, jaw relaxation, position of vocal cords, degree of coughing and limb movement. Mean arterial pressure (MAP) and heart rate (HR) measured noninvasively before induction of anaesthesia to 5 min after intubation (seven time points). RESULTS: Tracheal intubation was successful in all patients without requiring neuromuscular blocking agent. Intubating conditions were clinically acceptable in 10 of 20 patients (50%) in Gp I compared with 18 of 20 patients (90%) in Gp II (P < 0.05). MAP and HR decreased in both groups after induction of anaesthesia (P < 0.01). Both HR and MAP were significantly lower in Gp II compared with Gp I after tracheal intubation (P < 0.01). No patient in the present study developed bradycardia or hypotension. CONCLUSIONS: We conclude that remifentanil (3 microg.kg(-1)), administered before propofol (3 mg.kg(-1)) provides acceptable tracheal intubating conditions in children, and completely inhibited the increase in HR and MAP associated with intubation.

Adenoidectomy↗
PubMed1999

Distribution of glycogen phosphorylase and cytochrome oxidase in the central nervous system of the turtle Trachemys dorbigni.

Glycogen phosphorylase (GP) and cytochrome oxidase (CO) activities were mapped histochemically in the brain of the turtle Trachemys dorbigni. In the telencephalon, both activities occurred in the olfactory bulb, in all cortical areas, in the dorsal ventricular ridge, striatum, primordium hippocampi and olfactory tubercle. In the diencephalon, they were identified in some areas of the hypothalamus, and in rotundus and geniculate nuclei. Both reactions were detected in the oculomotor, trochlear, mesencephalic trigeminal nuclei, the nucleus of the posterior commissure, torus semicircularis, substantia nigra and ruber and isthmic nuclei of the mesencephalon. In all layers of the optic tectum GP activity was found, but CO only labelled the stratum griseum centrale. In the medulla oblonga both enzymes appear in the reticular, raphe and vestibular nuclei, locus coeruleus and nuclei of cranial nerves. In the cerebellum, the granular and molecular layers, and the deep cerebellar nuclei were positive for both enzymes. The Purkinje cells were only reactive for CO. In the spinal cord, motor and commissural neurones exhibited a positive reaction for the two enzymes. However, CO also occurred in the marginal nucleus and in the lateral funiculus. These results may be useful as a basis for subsequent studies on turtle brain metabolism.

Animals↗
PubMed1989

Genetic analysis of new restriction fragment length polymorphisms (RFLP) in the human IgH constant gene locus.

The human immunoglobulin heavy chain constant gene locus (IGHC) is polymorphic at both the protein (Gm and A2m allotypes) and the DNA level [RFLP for the gamma genes (IGHG), the switch mu region (IGHSM) and the switch alpha regions (IGHSA)]. The polymorphisms have been a valuable tool for assessment of the IGHC locus organization and a variety of population genetics and immunological investigations. In this study three new probes, identifying regions related to the IGHG (IGHPG and IGHSG) or IGHA (IGHAT) genes, have been employed to describe 11 different loci, 6 of which were polymorphic. Most of the polymorphisms are probably due to short insertions/deletions, particularly the SG regions, due to their repetitive structure. Ten loci were assigned to the IGHC region on the basis of known restriction maps, deletion mapping and association with mapped RFLP; the 11th, despite a striking sequence similarity with the IGHPG regions, could not be assigned to any known IGHC subregion. Analysis of these and previously known IGHG RFLP in a sample of 65 unrelated subjects plus 15 families allowed us to draw a genetic map, with particularly high resolution in the GP-G2-G4 genes region, revealing a marked discontinuity in the linkage disequilibrium values between pairs of adjacent loci.

Biological Evolution↗
PubMed1993

Cross-protection against lymphocytic choriomeningitis virus mediated by a CD4+ T-cell clone specific for an envelope glycoprotein epitope of Lassa virus.

Recombinant vaccinia virus expressing the Lassa virus (LV) envelope glycoprotein precursor, V-LSGPC, was used to study the basis of LV-induced cross-protective immunity against the closely related arenavirus lymphocytic choriomeningitis virus (LCMV). C3H/HeJ mice primed with V-LSGPC developed neither circulating antibodies nor CD8+ cytotoxic T cells specific for LCMV, yet they resisted a normally lethal LCMV challenge. Spleen cells from such mice gave a proliferative response to LCMV in vitro that was inhibitable by anti-CD4 antibody. Synthetic peptides corresponding to predicted T-cell sites common to the envelope glycoprotein precursor (GP-C) of LV and that of LCMV were used to map the specificity of the proliferative response to an epitope located between amino acids 403 and 417 of LV GP-C. Several CD4+ T-cell clones specific for the 403-417 peptide were isolated and found to produce gamma interferon in response to both the peptide and LCMV. One of these clones, C9, was selected for further study. C9 lysed I-AK-bearing target cells, and when adoptively transferred to C3H/HeJ mice, it was capable of mediating both a peptide-specific delayed hypersensitivity reaction and resistance to lethal LCMV challenge. These collective findings demonstrate, for the first time, that CD4+ T cells can play a major role in arenavirus-specific cross-protective immunity.

Amino Acid Sequence↗
PubMedDate not supplied

Blood-brain barrier permeation models: discriminating between potential CNS and non-CNS drugs including P-glycoprotein substrates.

The aim of this article is to present the design of a large heterogeneous CNS library (approximately 1700 compounds) from WDI and mapping CNS drugs using QSAR models of blood-brain barrier (BBB) permeation and P-gp substrates. The CNS library finally includes 1336 BBB-crossing drugs (BBB+), 259 molecules non-BBB-crossing (BBB-), and 91 P-gp substrates (either BBB+ or BBB-). Discriminant analysis and PLS-DA have been used to model the passive diffusion component of BBB permeation and potential physicochemical requirement of P-gp substrates. Three categories of explanatory variables (Cdiff, BBBpred, PGPpred) have been suggested to express the level of permeation within a continuous scale, starting from two classes data (BBB+/BBB-), allowing that the degree to which each compound belongs to an activity class is given using a membership score. Finally, statistical data analyses have shown that some very simple descriptors are sufficient to evaluate BBB permeation in most cases, with a high rate of well-classified drugs. Moreover, a "CNS drugs" map, including P-gp substrates and accurately reflecting the in vivo behavior of drugs, is proposed as a tool for CNS drug virtual screening.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Following passage through the oviduct, the coelomic envelope of Discoglossus pictus (amphibia) acquires fertilizability upon reorganization, conversion of gp 42 to gp 40, extensive glycosylation, and formation of a specific layer.

This paper describes the morphological and biochemical changes in Discoglossus pictus coelomic oocyte envelope (CE) following passage through the oviduct. As in other anurans, in this species, the transformation of the envelope into vitelline envelope (VE) leads to the acquisition of fertilizability and involves the cleavage of a glycoprotein. In addition, several features, typical of Discoglossus pictus, were observed. A new layer, VE-D, forms underneath the VE region facing the site of sperm entrance, the dimple. In the VE, arrowhead-like bundles of fibrils are perpendicularly oriented toward the dimple. Ultrastructural observations and staining with UEA-I suggested that VE-D might have a role in supporting sperm penetration into the dimple by orienting VE bundles and exposing sugar residues such as fucose. In 'in vitro' tests, VE binding of sperm occurs only if sperm are exposed to A23187, in agreement with previous data (Campanella et al., 1997: Mol Reprod Dev 47:323-333). Sperm binding occurs all over the VE. Accordingly, extracts of the VE covering the animal or the vegetal hemisphere have the same affinity to lectins (DBA, DSA, GNA, MAA, SBA, SNA, UEA-I, WGA). The CE contains six main glycoproteins. Peptide mapping indicated that during CE transformation into VE, gp 42 shifts to an apparent M(r) of 40 and gp 61 is converted to an apparent M(r) of 63 kDa. Lectin blot analyses showed extensive changes in cross-reactivity of most glycoproteins during the CE-->VE transition. The fact that DBA and UEA-I stain gp 63 rather than gp 61 and that this change is related only to gp 63, suggested that O-glycosylation and terminal fucose might be acquired by gp 63 in preparation of fertilization. Gp 63 has recently been cloned (Vaccaro et al., submitted) and shown to exhibit high homology to Xenopus gp 69/64, a VE sperm ligand (Tian et al., 1997a: J. Cell Biol. 136: 1099-1108; Tian et al., 1997b: Dev Biol 187:143-153), and to ZP2 of mammals.

Animals↗
PubMed2002

Covalent modifications of the ebola virus glycoprotein.

The role of covalent modifications of the Ebola virus glycoprotein (GP) and the significance of the sequence identity between filovirus and avian retrovirus GPs were investigated through biochemical and functional analyses of mutant GPs. The expression and processing of mutant GPs with altered N-linked glycosylation, substitutions for conserved cysteine residues, or a deletion in the region of O-linked glycosylation were analyzed, and virus entry capacities were assayed through the use of pseudotyped retroviruses. Cys-53 was the only GP(1) ( approximately 130 kDa) cysteine residue whose replacement resulted in the efficient secretion of GP(1), and it is therefore proposed that it participates in the formation of the only disulfide bond linking GP(1) to GP(2) ( approximately 24 kDa). We propose a complete cystine bridge map for the filovirus GPs based upon our analysis of mutant Ebola virus GPs. The effect of replacement of the conserved cysteines in the membrane-spanning region of GP(2) was found to depend on the nature of the substitution. Mutations in conserved N-linked glycosylation sites proved generally, with a few exceptions, innocuous. Deletion of the O-linked glycosylation region increased GP processing, incorporation into retrovirus particles, and viral transduction. Our data support a common evolutionary origin for the GPs of Ebola virus and avian retroviruses and have implications for gene transfer mediated by Ebola virus GP-pseudotyped retroviruses.

3T3 Cells↗
PubMed1983

An electrophysiological characterization of projections from the pedunculopontine area to entopeduncular nucleus and globus pallidus in the cat.

Stimulation of the pedunculopontine region (PPN), in which neurons are filled by horseradish peroxidase injected into the entopeduncular nucleus (ENTO) or globus pallidus (GP) of the cat, excites ENTO and GP neurons both orthodromically and antidromically. Stimulus threshold mapping experiments and intracellular records of EPSPs provide evidence that the orthodromic excitation may be produced monosynaptically by the axons of PPN neurons. Antidromic excitation of ENTO axons from stimulation in PPN or the thalamus may elicit IPSPs in ENTO neurons via the action of recurrent collaterals. An excitatory synaptic action of PPN neurons on pallidal cells could be a partial basis for the high discharge rate characteristic of these neurons in awake animals.

Afferent Pathways↗
PubMed2001

Induction of Fos-like immunoreactivity in the basal ganglia by ether anaesthesia: effects of injections of muscimol in rostral versus caudal substantia nigra pars reticulata.

Exposing rats to ether anaesthesia for 20 min induced a massive expression of c- fos like (FL) immunoreactivity in specific regions of the brain, including the basal ganglia. This expression of FL immunoreactivity in the basal ganglia was successfully blocked by local injections of muscimol (GABA(A) agonist) in the substantia nigra (SN). This model was used to investigate our recent finding that inhibition of caudal SN pars reticulata (SNpr) with muscimol is more potent in suppressing the motor component of tonic seizures than comparable inhibition of the rostral part. Two experiments were carried out. In experiment I, the effects of ether anaesthesia on c- fos expression in the brain were investigated. Brain sections taken from untreated control rats and stained immunocytochemically with c- fos antibodies. The results showed no FL immunoreactivity in the SNpr, subthalamic nucleus (STN), entopeduncular nucleus (EPN) and globus pallidus (GP). However, a few scattered FL immunoreactive nuclei were observed in the caudate-putamen (CPu). In rats exposed to ether, numerous FL immunoreactive nuclei were detected in the SNpr, STN, EPN and GP. In the CPu, a slight increase in number of labelled nuclei was noted. In experiment II, rats were prepared with intracranial chronic cannulae through which the effects of muscimol (60 ng) injected unilaterally in either the rostral or caudal SNpr on c- fosexpression induced by ether were investigated. Injections in both sites caused remarkable suppression of the ether-induced c- fos throughout the ipsilateral SNpr; however, the rostral injection also inhibited the expression of c- fos in the STN, EPN and GP. The implications of these results for microinjection mapping studies of the SN are discussed.

Anesthetics, Inhalation↗
PubMed2000

Identification of the peptide-binding site in the heat shock chaperone/tumor rejection antigen gp96 (Grp94).

Heat shock protein (HSP)-peptide complexes from tumor cells elicit specific protective immunity when injected into inbred mice bearing the same specific type of tumor. The HSP-mediated specific immunogenicity also occurs with virus-infected cells. The immune response is solely due to endogenous peptides noncovalently bound to HSP. A vesicular stomatitis virus capsid-derived peptide ligand bearing a photoreactive azido group was specifically bound by and cross-linked to murine HSP glycoprotein (gp) 96. The peptide-binding site was mapped by specific proteolysis of the cross-links followed by analysis of the cross-linked peptides using a judicious combination of SDS-gel electrophoresis, mass spectrometry, and amino acid sequencing. The minimal peptide-binding site was mapped to amino acid residues 624-630 in a highly conserved region of gp96. A model of the peptide binding pocket of gp96 was constructed based on the known crystallographic structure of major histocompatibility complex class I molecule bound to a similar peptide. The gp96-peptide model predicts that the peptide ligand is held in a groove formed by alpha-helices and lies on a surface consisting of antiparallel beta-sheets. Interestingly, in this model, the peptide binding pocket abuts the dimerization domain of gp96, which may have implications for the extraordinary stability of peptide-gp96 complexes, and for the faithful relay of peptides to major histocompatibility complex class I molecule for antigen presentation.

Amino Acid Sequence↗
PubMed2003

The delayed perfusion sign at MRI.

PURPOSE: Effective collateral blood flow seem to be an important factor associated with a small infarct volume and a good clinical outcome. We aimed to assess leptomeningeal collateral blood flow on source perfusion-weighted images in patients with acute stroke. MATERIALS AND METHODS: 29 patients with proximal middle cerebral artery occlusion (MCA alone, n=17; MCA + internal carotid artery [ICA] occlusion, n=12) were evaluated with MRI at baseline before thrombolytic therapy, and at day 60. Clinical evaluation was performed at days 0 and 60 with the National Institutes of Health Stroke Scale (NIHSS) score, and at day 60 with the modified Rankin score. We assessed (on source images of the dynamic contrast-enhanced T2*-weighted perfusion [PWI] sequence) the presence of a hypointensity consistent with delayed contrast arrival within the global perfusion deficit (delayed perfusion sign). We analyzed the extent of the area demonstrating such delayed perfusion (DP area) on source images of the PWI sequence, and compared it with the global perfusion (GP) abnormality shown by time-to-peak maps. We calculated the Spearman rank correlation coefficient between the DP/GP ratio and: 1. age; 2. clinical scores; 3. site of occlusion [MCA alone versus ICA+MCA occlusion]; 4. DWI lesion size at day 0, and T2WI lesion size at day 60; 5. PWI-derived parameters (time-to-peak [TTP], relative cerebral blood volume [rCBV], relative cerebral blood flow [rCBF], and peak height). All tests were bilateral and a p value<0.05 was considered as significant. RESULTS: Delayed perfusion areas of various size were found within the global perfusion deficit in all patients. High DP/GP ratio values were significantly correlated with: 1. better clinical scores at day 0 and day 60 (all p<=0.04); 2. smaller lesions at day 0 DWI and at day 60 T2WI (all p<=0.004); 3. ICA patency (r=0.49, p=0.01); 4. lower TTP delays, and higher values of rCBV, rCBF, and peak height. CONCLUSION: These preliminary data suggest that a delayed contrast filling observed on native perfusion-weighted images may be a marker of leptomeningeal collateral blood flow, and may lead to better clinical and morphological outcomes in acute ischemic stroke.

Acute Disease↗
PubMed1989

Influence of the rate of infusion on cyclosporine nephrotoxicity in the rat.

The effect of the rate of infusion of single and multiple doses of cyclosporine (CsA) on renal function was evaluated in Sprague-Dawley rats. CsA was dissolved in cremophore (Crem) or Tween 80 (Tween) and infused over consecutive 10-min periods at doses of 10, 20, 30 and 40 mg/kg. CsA-Crem and CsA-Tween produced similar and progressive changes in MAP, RBF, and RVR. By the end of the infusion, the mean values (% of control) of MAP (122 +/- 16% and 131 +/- 22%), RBF (56 +/- 11% and 66 +/- 20%), and RVR (222 +/- 38% and 232 +/- 134%) were significantly different from their respective preinfusion values. Infusion of Crem alone resulted in renal vasodilation at low doses and renal vasoconstriction at high doses. Vasoconstriction was not produced by infusion of Tween alone. In addition, animals were treated with vehicle alone (Gp 1), CsA 10 mg/kg/day by injection (Gp 2), or CsA 20 mg/kg/day by i.v. infusion over 4 hr (Gp 3), and were studied at 1 week. Systemic toxicity was greater with the 4-hr infusion as judged by an increase in MAP. The mean values of MAP were 107 +/- 8 (Gp 1), 101 +/- 13 (Gp 2), and 135 +/- 5 mm Hg (Gp 3; p less than 0.05). However, renal function was less severely affected with the 4-hr infusion. The mean values of CIn were 434 +/- 99 (Gp 1), 298 +/- 101 (Gp 2; p less than 0.05), and 425 +/- 114 microL/min/100 g BW (Gp 3); and the mean values for RBF were 2.72 +/- 0.74 (Gp 1), 2.08 +/- 0.17 (Gp 2; p less than 0.05), and 3.35 +/- 0.61 mL/min/100 g BW (Gp 3), respectively. Microangiograms showed marked abnormalities in the intrarenal perfusion pattern in the rats injected with CsA, 10 mg/kg BW. In rats infused over 4 hr with CsA, 20 mg/kg BW, the microangiographic pattern was normal. These studies demonstrate that the acute hemodynamic effects of CsA are directly related to the rate of infusion. Furthermore, the renal toxicity which follows repetitive injection of CsA can be minimized or avoided by administering CsA as a slow infusion. In addition to the total dose administered, the rate of infusion is an important determinant of nephrotoxicity.

Animals↗
PubMed1991

Isolation and characterization of corticostatic peptides from guinea pig bone marrow.

Three corticostatic peptides (GP-CS1, GP-CS2 and GP-CS3) were purified from extracts of guinea pig bone marrow. Each was identified on the basis of their ability to inhibit the secretion of corticosterone by isolated rat adrenal cells stimulated by ACTH. GP-CS1 and GP-CS2 were found to be 31 residues in length, rich in arginine and to have six cysteines typical of the corticostatin/defensin family of peptides previously purified from phagocytic cells of the immune system. GP-CS1 was found to be identical to GP-CS2 except for having a leucine at position 21 instead of isoleucine. GP-CS3 was also found to be rich in arginine and cysteine but structurally distinct from the other peptides. A combination of endoprotease mapping, ion-spray mass spectrometry and gas-phase sequencing revealed that GP-CS3 was a novel homo-dimer consisting of two 13 amino acid residue subunits cross-linked through eight cysteines in an anti-parellel configuration.

Adrenal Glands↗
PubMed1989

Health care provision and access opportunity in Madras city.

This short paper has reported on the health care provision and access opportunity in Madras city, India, using three city areas as sample areas. Maps have indicated that a general concentration of both GP and specialist practices, although access opportunities in the peripheries do not point up to paucity of services. The study is a report on private practices that is an important element in the health services provision.

Delivery of Health Care↗
PubMed1998

Surveillance of influenza-like illness in France. The example of the 1995/1996 epidemic.

STUDY OBJECTIVES: To discover if continuous computerised collection of morbidity data through a medical practice based sentinel network can be used to monitor influenza-like illness (ILI) epidemics. To obtain rough estimates of influenza vaccine effectiveness. DESIGN: Continuous passive surveillance of ILI through a computerised network of voluntary sentinel general practitioners (SGPs) in France (Sentinelle system). SETTING: Five hundred SGPs practices. PARTICIPANTS: Since 1984, SGPs updated a database with information on eight communicable diseases including ILI, via videotext terminals. Each ILI case is defined by the association of a sudden fever of 39 degrees C or above, respiratory symptoms, and myalgias. An ILI epidemic is detected when the national weekly incidence rate exceeds a seasonal threshold for two successive weeks. MAIN RESULTS: An ILI epidemic was reported from November 1995 to January 1996. In total, 13,951 individual cases were reported by SGPs during the epidemic period. The size of the epidemic (number of patients consulting a GP) was estimated to be 2,370,000 subjects. Maps of the epidemic showed that all regions have reported a high level ILI activity. The attack rate was the highest in school age children (13.5/100) and decreased as the age rose. Nearly 6% of the reported ILI cases among adults and elderly were vaccinated. The flu vaccine effectiveness against ILI was estimated to be 66% (95% CI 73%, 92%), ranging between 83% (95% CI 73%, 92%) among the subjects aged 15 to 24 years old to 16% (95% CI -12%, 44%) among the subjects aged 75 years or older. CONCLUSIONS: The Sentinelle system demonstrated adequate sensitivity and timeliness regarding ILI epidemic. Moreover, results of the monitoring were made available on the internet to increase the dissemination of information. Also, estimates of influenza vaccine effectiveness have been easily obtained. Altogether, they represent key points for the control of crisis situation such as ILI epidemics or pandemics.

Adolescent↗