An algorithm to determine the date when the McDonald criteria are met for the diagnosis of relapsing-remitting multiple sclerosis.

BACKGROUND: A patient is diagnosed with multiple sclerosis once they meet the McDonald criteria of dissemination in space and time. Studies of cohorts of patients with multiple sclerosis need a reproducible way to determine an accurate date of diagnosis. We developed an automatic data-driven algorithm to determine the date when the MacDonald criteria are met, which we validated with the Registre Lorrain des Scleroses en Plaques (ReLSEP), a regional French registry of patients with multiple sclerosis. METHODS: We developed an algorithm to determine the date of diagnosis based on clinical and paraclinical data adapted from the four versions of the McDonald criteria. For validation, the dates of diagnosis generated by the algorithm were compared with those determined by an expert physician using the patients' files as the gold standard. We calculated the sensitivity and specificity of the algorithm to provide a date, then we tested the equivalence between the dates of the gold standard and the algorithm (two-one-sided-t-test). RESULTS: The algorithm used every possibility of determining dissemination in space and time according to the four sets. The sensitivity of the algorithm was 100% for the four sets, and specificity ranged between 95 and 100%. The difference between the dates of diagnosis found by the physician and the algorithm was usually less than 2 weeks (equivalence test P<0.0001). CONCLUSION: The algorithm appears to be an efficient surrogate to accurately determine dates of diagnosis of multiple sclerosis in datasets of patients.

Visual phenomena and anatomo-electro-clinical correlations in occipital lobe seizures.

BACKGROUND: Occipital lobe seizure are underrepresented in epilepsy surgery cases series. This may reflect the fear for post-surgical functional deficits but also the doubt about the ability of anatomo-electro-clinical correlations to localize precisely the epileptogenic zone in occipital lobe seizure. METHODS: In this expert opinion paper, we review first the general clinical characteristics of occipital lobe seizures, describe the repertoire of visual phenomena and oculo-motor signes in occipital seizures, describe inter-ictal and ictal EEG and finally the possible schemes of epileptogenic zone organization. RESULTS: Visual and oculo-motor semiology points towards occipital onset seizures but is neither pathognomonic nor constant. Eyes version and unilateral ictal discharge have a strong lateralizing value but inter-ictal spikes as well as eyes version can be falsely lateralizing. CONCLUSION: Although visual and oculo-motor phenomena are characteristic of occipital lobe seizures, they may be discrete, overlooked and should therefore be carefully assessed. There are no clear electro-clinical correlations of a sublobar organization of occipital seizures but the clinical pattern of propagation might help to differentiate complex occipito-temporal from occipito-parietal initial epileptogenic network.

Short communication: Genetic parameters for milk protein composition predicted using mid-infrared spectroscopy in the French Montbéliarde, Normande, and Holstein dairy cattle breeds.

Genetic parameters for the major milk proteins were estimated in the 3 main French dairy cattle breeds (i.e. Montbéliarde, Normande, and Holstein) as part of the PhénoFinlait program. The 6 major milk protein contents as well as the total protein content (PC) were estimated from mid-infrared spectrometry on 133,592 test-day milk samples from 20,434 cows in first lactation. Lactation means, expressed as a percentage of milk (protein contents) or of protein (protein fractions), were analyzed with an animal mixed model including fixed environmental effects (herd, year × month of calving, and spectrometer) and a random genetic effect. Genetic parameter estimates were very consistent across breeds. Heritability estimates (h2) were generally higher for protein fractions than for protein contents. They were moderate to high for αS1-casein, αS2-casein, ß-casein, κ-casein, and α-lactalbumin (0.25 < h2 < 0.72). In each breed, ß-lactoglobulin was the most heritable trait (0.61 < h2 < 0.86). Genetic correlations (rg) varied depending on how the percentage was expressed. The PC was strongly positively correlated with protein contents but almost genetically independent from protein fractions. Protein fractions were generally in opposition, except between κ-casein and α-lactalbumin (0.39 < rg < 0.46) and κ-casein and αS2-casein (0.36 < rg < 0.49). Between protein contents, rg estimates were positive, with highest values found between caseins (0.83 < rg < 0.98). In the 3 breeds, ß-lactoglobulin was negatively correlated with caseins (-0.75 < rg < -0.08), in particular with κ-casein (-0.75 < rg < -0.55). These results, obtained from a large panel of cows of the 3 main French dairy cattle breeds, show that routinely collected mid-infrared spectra could be used to modify milk protein composition by selection.

The cross-national epidemiology of DSM-IV intermittent explosive disorder.

BACKGROUND: This is the first cross-national study of intermittent explosive disorder (IED). METHOD: A total of 17 face-to-face cross-sectional household surveys of adults were conducted in 16 countries (n = 88 063) as part of the World Mental Health Surveys initiative. The World Health Organization Composite International Diagnostic Interview (CIDI 3.0) assessed DSM-IV IED, using a conservative definition. RESULTS: Lifetime prevalence of IED ranged across countries from 0.1 to 2.7% with a weighted average of 0.8%; 0.4 and 0.3% met criteria for 12-month and 30-day prevalence, respectively. Sociodemographic correlates of lifetime risk of IED were being male, young, unemployed, divorced or separated, and having less education. The median age of onset of IED was 17 years with an interquartile range across countries of 13-23 years. The vast majority (81.7%) of those with lifetime IED met criteria for at least one other lifetime disorder; co-morbidity was highest with alcohol abuse and depression. Of those with 12-month IED, 39% reported severe impairment in at least one domain, most commonly social or relationship functioning. Prior traumatic experiences involving physical (non-combat) or sexual violence were associated with increased risk of IED onset. CONCLUSIONS: Conservatively defined, IED is a low prevalence disorder but this belies the true societal costs of IED in terms of the effects of explosive anger attacks on families and relationships. IED is more common among males, the young, the socially disadvantaged and among those with prior exposure to violence, especially in childhood.

Geographical distribution of Angiostrongylus vasorum in foxes (Vulpes vulpes) in the Republic of Ireland.

The reported incidence of the metastrongylid nematode Angiostrongylus vasorum, that infects dogs and other canids, is increasing worldwide outside recognized endemic foci. This apparent expansion of the parasite's range is causing concern to veterinary clinicians as the disease caused in dogs can be life threatening and its treatment is not straightforward. The red fox is thought to be a reservoir host for dogs. To investigate the spatial distribution of infection in foxes in Ireland, the hearts and lungs of 542 foxes from all over Ireland were examined. The incidence of infection was found to be 39·9% [95% confidence interval (CI) 35·7-44·1] with positive samples occurring in each of the country's 26 counties. This report confirms that the parasite is endemic in Ireland and the overall prevalence is the second highest in Europe. This is the first survey of A. vasorum infection in Irish foxes and highlights the potential exposure of the Irish dog population to high risk of cross-infection. Additionally, Crenosoma vulpis was found in seven of the foxes, a parasite not previously reported in the Irish fox.

Whole-genome scan to detect quantitative trait loci associated with milk protein composition in 3 French dairy cattle breeds.

In the context of the PhénoFinLait project, a genome-wide analysis was performed to detect quantitative trait loci (QTL) that affect milk protein composition estimated using mid-infrared spectrometry in the Montbéliarde (MO), Normande (NO), and Holstein (HO) French dairy cattle breeds. The 6 main milk proteins (α-lactalbumin, ß-lactoglobulin, and αS1-, αS2-, ß-, and κ-caseins) expressed as grams per 100g of milk (% of milk) or as grams per 100g of protein (% of protein) were estimated in 848,068 test-day milk samples from 156,660 cows. Genotyping was performed for 2,773 MO, 2,673 NO, and 2,208 HO cows using the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA). Individual test-day records were adjusted for environmental effects and then averaged per cow to define the phenotypes analyzed. Quantitative trait loci detection was performed within each breed using a linkage disequilibrium and linkage analysis approach. A total of 39 genomic regions distributed on 20 of the 29 Bos taurus autosomes (BTA) were significantly associated with milk protein composition at a genome-wide level of significance in at least 1 of the 3 breeds. The 9 most significant QTL were located on BTA2 (133 Mbp), BTA6 (38, 47, and 87 Mbp), BTA11 (103 Mbp), BTA14 (1.8 Mbp), BTA20 (32 and 58 Mbp), and BTA29 (8 Mbp). The BTA6 (87 Mbp), BTA11, and BTA20 (58 Mbp) QTL were found in all 3 breeds, and they had highly significant effects on κ-casein, ß-lactoglobulin, and α-lactalbumin, expressed as a percentage of protein, respectively. Each of these QTL explained between 13% (BTA14) and 51% (BTA11) of the genetic variance of the trait. Many other QTL regions were also identified in at least one breed. They were located on 14 additional chromosomes (1, 3, 4, 5, 7, 15, 17, 19, 21, 22, 24, 25, 26, and 27), and they explained 2 to 8% of the genetic variance of 1 or more protein composition traits. Concordance analyses, performed between QTL status and sequence-derived polymorphisms from 13 bulls, revealed previously known causal polymorphisms in LGB (BTA11) and GHR (BTA20 at 32 Mbp) and excluded some other previously described mutations. These results constitute a first step in identifying causal mutations and using routinely collected mid-infrared predictions in future genomic selection programs to improve bovine milk protein composition.

A dystrophic muscle broadens the contribution and activation of immune cells reacting to rAAV gene transfer.

Recombinant adeno-associated viral vectors (rAAVs) are used for therapeutic gene transfer in skeletal muscle, but it is unclear if immune reactivity to gene transfer and persistence of transgene are affected by pathologic conditions such as muscular dystrophy. Thus, we compared dystrophic mice devoid of α-sarcoglycan with healthy mice to characterize immune cell activation and cellular populations contributing to the loss of gene-modified myofibers. Following rAAV2/1 delivery of an immunogenic α-sarcoglycan reporter transgene in the muscle, both strains developed strong CD4 and CD8 T-cell-mediated immune responses in lymphoid organs associated with muscle CD3+ T and CD11b+ mononuclear cell infiltrates. Selective cell subset depletion models revealed that CD4+ T cells were essential for transgene rejection in both healthy and pathologic mice, but macrophages and CD8+ T cells additionally contributed as effector cells of transgene rejection only in dystrophic mice. Vectors restricting transgene expression in antigen-presenting cells showed that endogenous presentation of transgene products was the sole mechanism responsible for T-cell priming in normal mice, whereas additional and protracted antigenic presentation occurred in dystrophic animals, leading to secondary CD4+ T-cell activation and failure to maintain transgene expression. Therefore, the dystrophic environment diversifies cellular immune response mechanisms induced by gene transfer, with a negative outcome.

Genetic parameter estimation for major milk fatty acids in Alpine and Saanen primiparous goats.

Genetic parameters for 18 fatty acids or groups of fatty acids (FA), milk production traits, and somatic cell score (SCS) were estimated by restricted maximum likelihood with a repeatability animal model, using 45,259 test-day records from the first lactations of 13,677 Alpine and Saanen goats. Fatty acid data were collected as part of an extensive recording scheme (PhénoFinLait), and sample testing was based on mid-infrared spectra estimates. The total predicted FA content in milk was approximately 3.5% in Alpine and Saanen goats. Goat milk fat showed similar saturated FA to cattle and sheep, but higher contents of capric (C10:0) FA (~ 9.7 g/100g of milk fat). Heritability estimates ranged from 0.18 to 0.49 for FA and estimates were generally higher when FA were expressed in g/100g of milk fat compared with g/100g of milk. In general, the 3 specific short- and medium-chain goat FA, caproic acid (C6:0), caprylic acid (C8:0), and especially capric (C10:0) acid, had among the highest heritability estimates (from 0.21 to 0.37; average of 0.30). Heritability estimates for milk yield, fat and protein contents, and SCS were 0.22, 0.23, 0.39, 0.09, and 0.24, 0.20, 0.40, and 0.15, in Alpine and Saanen goats, respectively. When FA were expressed in g/100g of milk, genetic correlations between fat content and all FA were high and positive. Genetic correlations between the fat content and FA groups expressed in g/100g of fat led to further investigation of the association between fat content and FA profile within milk fat. Accordingly, in both Saanen and Alpine breeds, no significant genetic correlations were found between fat content and C16:0, whereas the correlations between fat content and specific goat FA (C6:0 to C10:0) were positive (0.17 to 0.59). In addition, the genetic correlation between fat content and C14:0 was negative (-0.17 to -0.35). The values of the genetic correlations between protein content and individual FA were similar, although genetic correlations between protein content and FA groups were close to zero. Genetic correlations of milk yield or SCS with the FA profile were weak. Results for genetic parameters for FA, however, should be further validated, because the low predicting ability of certain FA using mid-infrared spectra and the limited calibration data set might have resulted in low accuracy. In conclusion, our results indicated substantial genetic variation in goat milk FA that supported their amenability for genetic selection. In addition, selection on protein and fat contents is not expected to have an undesirable effect on the FA profile in regard to specificity of goat products and human health.

Epilepsy surgery for drug-resistant temporal lobe epilepsy in over-50 year-olds: Seizure outcome, surgical complications and neuropsychological outcome.

OBJECTIVE: Surgery is an effective treatment for drug-resistant temporal-lobe epilepsy (TLE), but is still underutilized for older patients because of a perceived higher rate of perioperative complications, cognitive decline and worse seizure outcome. METHODS: We retrospectively screened all patients operated on in our institution for drug-resistant TLE between 2007 and 2019. Data of patients aged ≥50 years versus <50 years at surgery were compared. The primary endpoint was freedom from disabling seizure (Engel I) at 2 years postoperatively. RESULTS: In patients aged ≥50 years (n=19), mean age at surgery was 54.9 years and mean disease duration was 36.6 years. At 2 years postoperatively, rates of Engel I seizure outcome were not significantly different between the two groups (73.9% in the <50 years group versus 94.4% in the ≥50 years group). Although surgical complications were significantly (47.4%) in the older patients, neurological deficit was permanent in only 5.3% of cases. At 1 year postoperatively, neuropsychological outcome did not significantly differ between the two groups. CONCLUSIONS: Patients aged ≥50 years had an excellent seizure outcome at 2 years postoperatively. Early postoperative complications were more frequent in patients aged ≥50 years but were mostly transient. Cognitive outcome was similar to that in younger patients. These findings strongly suggest that age ≥50 years should not be an exclusion criterion for resective epilepsy surgery in patients with drug-resistant TLE.

Quantification of lentiviral vector copy numbers in individual hematopoietic colony-forming cells shows vector dose-dependent effects on the frequency and level of transduction.

Lentiviral vectors are effective tools for gene transfer and integrate variable numbers of proviral DNA copies in variable proportions of cells. The levels of transduction of a cellular population may therefore depend upon experimental parameters affecting the frequency and/or the distribution of vector integration events in this population. Such analysis would require measuring vector copy numbers (VCN) in individual cells. To evaluate the transduction of hematopoietic progenitor cells at the single-cell level, we measured VCN in individual colony-forming cell (CFC) units, using an adapted quantitative PCR (Q-PCR) method. The feasibility, reproducibility and sensitivity of this approach were tested with characterized cell lines carrying known numbers of vector integration. The method was validated by correlating data in CFC with gene expression or with calculated values, and was found to slightly underestimate VCN. In spite of this, such Q-PCR on CFC was useful to compare transduction levels with different infection protocols and different vectors. Increasing the vector concentration and re-iterating the infection were two different strategies that improved transduction by increasing the frequency of transduced progenitor cells. Repeated infection also augmented the number of integrated copies and the magnitude of this effect seemed to depend on the vector preparation. Thus, the distribution of VCN in hematopoietic colonies may depend upon experimental conditions including features of vectors. This should be carefully evaluated in the context of ex vivo hematopoietic gene therapy studies.

The role of transferrin in actinide(IV) uptake: comparison with iron(III).

The impact of actinides on living organisms has been the subject of numerous studies since the 1950s. From a general point of view, these studies show that actinides are chemical poisons as well as radiological hazards. Actinides in plasma are assumed to be mainly complexed to transferrin, the iron carrier protein. This paper casts light on the uptake of actinides(IV) (thorium, neptunium, plutonium) by transferrin, focusing on the pH dependence of the interaction and on a molecular description of the cation binding site in the protein. Their behavior is compared with that of iron(III), the endogenous transferrin cation, from a structural point of view. Complementary spectroscopic techniques (UV/Vis spectrophotometry, microfiltration coupled with gamma spectrometry, and X-ray absorption fine structure) have been combined in order to propose a structural model for the actinide-binding site in transferrin. Comparison of our results with data available on holotransferrin suggests some similarities between the behavior of Fe(III) and Np(IV)/Pu(IV)/ Np(IV) is not complexed at pH <7, whereas at pH approximately 7.4 complexation can be regarded as quantitative. This pH effect is consistent with the in vivo transferrin "cycle". Pu(IV) also appears to be quantitatively bound by apotransferrin at around pH approximately 7.5, whereas Th(IV) was never complexed under our experimental conditions. EXAFS data at the actinide edge have allowed a structural model of the actinide binding site to be elaborated: at least one tyrosine residue could participate in the actinide coordination sphere (two for iron), forming a mixed hydroxo-transferrin complex in which actinides are bound with transferrin both through An-tyrosine and through An--OH bonds. A description of interatomic distances is provided.

Stability across environments of the coffee variety near infrared spectral signature.

Previous study on food plants has shown that near infrared (NIR) spectral methods seem effective for authenticating coffee varieties. We confirm that result, but also show that inter-variety differences are not stable from one harvest to the next. We put forward the hypothesis that the spectral signature is affected by environmental factors. The purpose of this study was to find a way of reducing this environmental variance to increase the method's reliability and to enable practical application in breeding. Spectral collections were obtained from ground green coffee samples from multilocation trials. Two harvests of bean samples from 11 homozygous introgressed lines, and the cv 'Caturra' as the control, supplied from three different sites, were compared. For each site, squared Euclidean distances among the 12 varieties were estimated from the NIR spectra. Matrix correlation coefficients were assessed by the Mantel test. We obtained very good stability (high correlations) for inter-variety differences across the sites when using the two harvests data. If only the most heritable zones of the spectrum were used, there was a marked improvement in the efficiency of the method. This improvement was achieved by treating the spectrum as succession of phenotypic variables, each resulting from an environmental and genetic effect. Heritabilities were calculated with confidence intervals. A near infrared spectroscopy signature, acquired over a set of harvests, can therefore effectively characterize a coffee variety. We indicated how this typical signature can be used in breeding to assist in selection.

Accuracy of patient-specific guided implantation of the glenoid component in reversed shoulder arthroplasty.

BACKGROUND: The aim of this study was to assess the accuracy of patient-specific guided glenoid component implantation in reverse shoulder arthroplasty. MATERIALS AND METHODS: 32 reverse shoulder arthroplasties were done using preoperative 3D planning and 4 patient-specific guides to prepare the glenoid and position the glenoid component. Baseplate version, inclination and entry point as well as angulation of the screws were compared to the preoperative plan measured on CT by independent observers. RESULTS: The mean deviation in baseplate version from the preoperative plan was 4.4°+3.1° (range, 0.3°-13.7°), in baseplate inclination 5.0°+4.2° (range, 0.1° to 14.5°) and in baseplate entry point 2.4mm+1.4mm (range, 0.4° to 6.3°). The average screw superior-inferior angulation deviation for the superior screw was 2.8°+2.6° (range, 0.0°-10.1°) and 2.8+2.6° in the antero-posterior plane (range, 0.1°-11.6°). For the inferior screw the superior-inferior angle deviation was 5.3°+3.8° (range, 0.1°-15.2°); the antero-posterior angle deviation was 4.1°+3.1° (range, 0.0°-9.8°). CONCLUSIONS: Patient-specific instrumentation (PSI) for the glenoid component in reverse shoulder arthroplasty allows the shoulder surgeon to accurately execute the preoperative 3D plan. LEVEL OF EVIDENCE: Level 3.

Return to recreational sport and clinical outcomes with at least 2years follow-up after arthroscopic repair of rotator cuff tears.

INTRODUCTION: The main objective of the study was to assess return to sports in recreational athletes after arthroscopic repair of rotator cuff tear (RCT). MATERIAL AND METHODS: A retrospective single-center study included all recreational athletes operated between 2008 and 2012 for arthroscopic repair of RCT, with regular sports activity, and aged less than 70 years. All were recontacted at a minimum follow-up of 2 years. The main outcome was return to sports (yes/no). The secondary criteria were return to sports, time to return to sports, number of hours per week of sports activity, and at the last follow-up the subjective assessment of sports level, patient satisfaction, and the Western Ontario Rotator Cuff (WORC) Index. RESULTS: Seventy-six patients (37 females, 39 males) with a mean age of 57.0±7.3 years were included. Of these 76 patients, 53 (69.7%) patients participated in a sport that specifically involved the upper limb. The mean follow-up was 45±14 months. Postoperatively, 67 of 76 (88.2%) patients returned to a sports activity, the same sport for 52 out of 76 (68.4%). The mean time to return to sports was 6±4.9 months. For patients who had taken up their sport again, the mean number of hours a week was not significantly modified (P=0.58). At the last follow-up, the subjective sports level was judged better or identical to the preoperative level by 52 of 67 (77.6%) patients. The factors significantly associated with absence of return to the previous sport were pain symptoms evolving for more than 9 months before surgery (OR=3.6 [1.01-12.5], P=0.04) and preoperative sports intensity less than 2h/week (OR=4.1 [1.4-12.3], P=0.01). At the last follow-up, the functional improvement evaluated by the WORC Index was strongly significant (P<0.00001) and 73 of 76 (96%) patients were satisfied. CONCLUSION: The majority of the recreational athletes returned to sports after arthroscopic rotator cuff repair, most often at the same level and with equivalent intensity compared to before surgery. LEVEL OF EVIDENCE: IV, retrospective study.

Comparison of three methods for the detection of Angiostrongylus vasorum in the final host.

Angiostrongylosis is potentially fatal parasitic nematode infection affecting dogs which can be difficult to diagnose. In recent years several microscopical, serological and molecular detection methods have been developed, however there are few studies that have compared the relative performance of these methods. Screening necropsy material from an opportunistic sample of 140 foxes (82 of which were considered to be infected with Angiostrongylus vasorum), indicated sensitivities of 84.1% for dissection and visual examination of plucks, 69.5% for nested PCR of an 18S rRNA fragment and 76.8% for a canine A. vasorum antigen detection test (IDEXX Angio Detect) of tissue fluid samples respectively. Agreement between the tests ranged from 45.6 to 79.7%. A novel nested PCR-RFLP for the detection and identification of canid lungworm spp. is described.

The PLA2R1-JAK2 pathway upregulates ERRα and its mitochondrial program to exert tumor-suppressive action.

Little is known about the biological role of the phospholipase A2 receptor (PLA2R1) transmembrane protein. In recent years, PLA2R1 has been shown to have an important role in regulating tumor-suppressive responses via JAK2 activation, but the underlying mechanisms are largely undeciphered. In this study, we observed that PLA2R1 increases the mitochondrial content, judged by increased levels of numerous mitochondrial proteins, of the mitochondrial structural component cardiolipin, of the mitochondrial DNA content, and of the mitochondrial DNA replication and transcription factor TFAM. This effect of PLA2R1 relies on a transcriptional program controlled by the estrogen-related receptor alpha1 (ERRα) mitochondrial master regulator. Expression of ERRα and of its nucleus-encoded mitochondrial targets is upregulated upon PLA2R1 ectopic expression, and this effect is mediated by JAK2. Conversely, downregulation of PLA2R1 decreases the level of ERRα and of its nucleus-encoded mitochondrial targets. Finally, blocking the ERRα-controlled mitochondrial program largely inhibits the PLA2R1-induced tumor-suppressive response. Together, our data document ERRα and its mitochondrial program as downstream effectors of the PLA2R1-JAK2 pathway leading to oncosuppression.

Multidrug resistance protein 3 loss promotes tumor formation by inducing senescence escape.

Oncogenic-stress-induced senescence (OIS) is a stress response allowing normal cells, when receiving oncogenic signals, to stably arrest their proliferation. OIS thus acts to prevent aberrant cell proliferation and tumor formation. To identify novel tumor suppressive pathways, we have recently completed a loss-of-function genetic screen to identify novel genes promoting escape from OIS and thus, potentially, tumor formation when their functions are lost. Using this approach, we unexpectedly found that loss of function of the multidrug resistance protein 3 (MRP3 or ABCC3) promotes escape from OIS in human epithelial cells. Importantly, ABCC3 expression is reduced in human skin tumors, and ABCC3-knockout mice display increased sensitivity to RAS-induced skin carcinogenesis, concomitantly with decreased OIS. ABCC3 participates in resistance to chemotherapy via its transporter activity. Our data show that this transporter activity is involved in ABCC3-induced senescence, demonstrating that this protein has a complex role in cancer, since its loss of function may promote escape from OIS and tumor formation whereas its gain of function promotes resistance to chemotherapy.

[Induced abortion in France: results of the COCON study]. / Prise en charge de l'IVG en France: résultats de l'enquête COCON.

OBJECTIVE: The aim of this article is to describe conditions of abortions practices in France. MATERIALS AND METHODS: The study was based on the COCON survey. This survey was carried out among a representative sample of 2863 women aged 18 to 44 living in metropolitan France. Women were interviewed by telephone. The analysis was performed among a sub-sample of 320 women who had had an abortion between 1996 and 2000. Results were compared with those of the national notification of induced abortions. RESULTS: Altogether, the way in which abortions were carried out was appropriate, but differences were observed according to the type of hospital: access to care was easier in the private sector; however a pre-abortion interview was less often carried out and a post-abortion interview less often proposed in the private sector. Besides, in both sectors, women were rarely allowed to choose the abortion technique, or the type of anesthesia in the case of a surgical abortion. CONCLUSION: The COCON study is the first population based survey describing the characteristics of care regarding voluntary abortion. It shows the persistence of differences in practices between the public and the private sectors.

Relationship between immunological structure and biochemical properties of human thyroid peroxidase.

Although the primary structure of human thyroid peroxidase (hTPO) has been recently deciphered, little is known about its spatial conformation. Such information is of crucial importance in any attempt to relate the structure with the function of hTPO. To probe the antigenic surface of hTPO and to correlate its immunological structure to its biochemical properties, we used 13 monoclonal antibodies (mAb) displaying various affinity for hTPO. Criss-cross experiments showed 7 clusters of reactivity which were interpreted as reflecting 7 epitopes on the surface of the hTPO molecule. Extending our analysis to partial and nonsymmetrical cross-reactivities, these epitopes were shown to be localized in 4 antigenic domains of the hTPO. We further investigated the nature of these 7 hTPO epitopes by testing mAb binding to peroxidases from various origins and chemically modified hTPO; 3 epitopes were shown to be evolutionary conserved, and 5 resistant to reduction and denaturation. We also analyzed the role of the hTPO epitopes in the enzymatic activity and autoimmune targeting of the molecule. Nine epitopes were shown to be localized at the vicinity of both catalytic sites as the binding of their respective mAb modulated the enzyme activity. Autoantibodies from patients presenting with autoimmune thyroid disorders were essentially directed to epitopes similar or adjacent to those recognized by 8 of the 13 mAb and present on only 2 antigenic domains of hTPO. Taken together these data allowed us to propose a tentative map of the surface of the hTPO molecule which associates its epitopic structure with its biochemical functions.

Bispecific thyroglobulin and thyroperoxidase autoantibodies in patients with various thyroid and autoimmune diseases.

Recent evidence indicates that thyroid autoimmune disorders are associated with the presence of circulating autoantibodies (aAb) with dual specificity for thyroglobulin (TG) and thyroperoxidase (TPO). The question of whether these aAb, called TGPO aAb, are of clinical relevance compared to TG and TPO aAb remains to be determined. The availability of purified preparations of human TG and TPO allowed the development of a specific and sensitive RIA for TGPO aAb in serum. In the present study, we compared levels of aAb that cross-react with both TG and TPO (TGPO aAb) and total TG and TPO aAb levels, respectively, in sera from 84 normal controls and 226 patients with various thyroid and autoimmune diseases, including nontoxic goiter (n = 50), toxic nodular goiter (n = 13), thyroid carcinoma (n = 20), primary idiopathic myxedema (n = 15), postpartum thyroiditis (n = 11), Hashimoto's thyroiditis (n = 38), pernicious anemia (n = 27), rheumatoid arthritis (n = 19), and insulin-dependent diabetes mellitus (n = 33). In addition, 16 patients with Hashimoto's thyroiditis were studied before therapy and after more than 3 months of treatment with L-T4. It was shown that TGPO aAb were generally, but not always, present in the serum of patients with Hashimoto's thyroiditis, which also contained TG and TPO aAb. In contrast, TGPO aAb were undetectable in normal controls (excepting a few cases reaching borderline levels) as well as in sera from the majority of the other patients tested. Selecting sera positive for TGPO and either TG or TPO aAb, a statistically significant correlation was found between TGPO and TG (n = 26; P < 0.005), but not TPO aAb. Interestingly, the TGPO aAb level significantly decreased in patients with Hashimoto's thyroiditis after hormonal therapy (P < 0.05), some of them shifting from TGPO aAb positive before treatment to negative after treatment. In conclusion, TGPO aAb determination distinguishes Hashimoto's patients from patients with either thyroid and/or autoimmune diseases. The specific presence of TGPO aAb in a subset of Hashimoto's patients and their variation during T4 therapy remain to be understood. This could give a clue to mechanisms of autoimmune thyroid disease.