[New recommendations for cervical cancer screening in France]. / Nouvelles recommandations pour le dépistage du cancer du col de l'utérus en France.

In France, recent advances in cervical cancer screening include an organized cervical cancer-screening program and the introduction of HPV testing as a first-line test for women aged 30-65 years. The HPV test, performed on a cervical smear taken by a health professional, could also be performed on a vaginal self-sample in certain indications. The detection kits used to test for HPV should target high-risk HPV, be validated for screening and meet the performance requirements for this indication. Although no longer used as a first-line test in women aged 30-65 years, cytological examination of cervical cells remains important, particularly in the triage of HPV positive women. The interest of other biological techniques, such as HPV genotyping, viral load, cellular expression of p16/Ki-67 proteins and the methylation of cellular or viral genes, still needs to be clarified, but they could help to refine the triage strategy of HPV-positive women and limit the need for colposcopy and unnecessary stress for patients.

[One case of type 1 auto-immune polyendocrinopathy or APECED]. / Polyendocrinopathie auto-immune de type 1 ou syndrome APECED.

INTRODUCTION: autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE). We report the case of a young girl with APECED. CASE REPORT: an 18 year-old girl born to consanguineous parents consulted for diffuse alopecia. Dermatological examination showed nail and dental enamel dystrophy and angular cheilitis. She had a history of mineralocorticoid deficiency (Addison's disease), hypoparathyroidism, hypogonadism and Biermer's disease, and she had also had chronic mucocutaneous candidiasis since childhood. She was presenting APECED with autoimmune endocrine failure, chronic mucocutaneous candidiasis and abnormalities of ectoderm-derived tissue. Analysis of mutation in the AIRE gene showed the c.769C>T homozygous mutation in exon 6. DISCUSSION: APECED, a rare autosomal recessive disorder, is a potentially life-threatening autoimmune disease. Chronic mucocutaneous candidiasis is a common and early feature in children. Dermatologists are likely to be the first physicians to diagnose this syndrome.

Spinal cord compression complicating aseptic spondylodiscitis in ankylosing spondylitis.

Aseptic spondylodiscitis is a well recognized complication of ankylosing spondylitis. Neurological complications of such discovertebral lesions are uncommon. We report a new case with a diagnosis of T12-L1 spondylodiscitis which developed ten years after a spinal cord compression. Such neurological complications of aseptic spondylodiscitis may be explained by proliferative epidural tissue without predominant inflammatory infiltrates and also the development of new bone reaction, suggesting the contribution of mechanical factors.

Selective dorsolateral frontal lobe dysfunction associated with diencephalic amnesia.

We report three cases with unilateral thalamic ischemic lesions that resulted in lasting material-specific memory impairments and concomitant selective frontal lobe-related cognitive deficits. In two cases the lesions were limited to the left thalamus, and in the third the right thalamus was involved. These deficits were associated with ipsilateral diencephalic, striatal, and dorsolateral prefrontal hypoperfusion. The damage implicated the ventral anterior nucleus, the mamillothalamic tract, and the rostroventral internal medullary lamina. These findings suggest that medial thalamic damage involving the ventral and rostral sector of the dorsal thalamus will concurrently affect functionally and neurally distinct limbodiencephalic pathways and diencephalic connections with the frontal cortex. A review of the neuropsychological and neuroimaging findings from previously reported cases with vascular lesions of the thalamus further supports this contention. The presence of frontal lobe-related cognitive deficits, though not obligatorily related to the memory problems, may contribute to some aspects of the memory deficits and affect the nature of the memory disorder observed in some cases with diencephalic amnesia.

Genetic resistance of Creole goats to cowdriosis in Guadeloupe. Status in 1995.

A genetic predisposition to resistance (R)/susceptibility (S) has been demonstrated for cowdriosis in certain goal lines. In order to identify genetic markers of R/S and to follow their transmission to the offspring, 4 groups of sires and dams were crossbred in 1991, 1992, and 1993: Rr, RS, SR, and SS. The offspring were challenged at the age of six months with subsequent challenge of the S parent. From 28 presumed S dams, 7 turned out R and from 2 presumed S sires, 1 was R and the other undefinable. The resistance rate was 76% for 21 RR kids and 45% for 20 RS kids. The R character seems to be better transmitted by dams than the S one. No difference was observed between R and S goats in terms of incubation period and body temperature level after challenge. There was no statistical effect found of sex, litter size, or birth mass on the R/S character; only a slight effect on daily mass gain was observed. Sperm has been collected from 4 S sires (died after challenge) and 5 R sires, and stored in liquid nitrogen in order to conceive additional SR and SS progeny. Several caprine leucocyte antigens seem to be genetic markers of R (Be 1, CLY) and of S (Be 9, Be 22, Be 23). Further powerful tools like microsatellites and probes defining other interesting loci possibly involved in disease pathogenesis are now at hand and will be included in future experiments.

Blood groups and protein polymorphisms in five goat breeds (Capra hircus).

Data on allele frequencies at six red cell blood group systems and three blood protein polymorphic loci in five goat breeds are reported. Two blood proteins, albumin and carbonic anhydrase, were not found to be polymorphic. The B blood group system of goats, like its homologue in cattle and sheep, is highly complex. At least 44 B phenogroups (haplotypes) have been distinguished in this study. Based on the variation in allele frequencies between breeds, genetic distances were calculated. The distances estimated by four different methods were in close agreement with data from the history and geographic origins of the breeds examined.

[Azithromycin and genital infections]. / Azithromycine et infections de la sphère génitale.

The lower genital tract infections due to Chlamydia trachomatis are frequent, essentially occurring in young patients, with possible complications and severe sequela, particularly in women where the sterility risk is one of the major consequences. If an effective treatment could be systematically proposed, a good compliance (easy administration and good toleration) is one of the key factor to success. In this context, the azithromycin displays numerous advantages. The azithromycin in vitro activity on Chl. trachomatis strains is permanent with MIC comprised between 0.06 and 0.125 micrograms/ml, with an activity equivalent to those of other macrolides, to tetracyclines and quinolones. Different animal models allow to demonstrate the curative activity of the azithromycin administered as a single dose, at dosage regimen equivalent to those used in man, and a prophylactic activity on the salpingitis onset in provoked Chl. trachomatis infections. Several comparative clinical studies with azithromycin administered as a 1 g single dose displayed very satisfactory results with 98% of bacterial eradication, identical to those obtained with reference treatment. On the other hand, restrictions to the product use are a less constant activity against Neisseria gonorrhoeae and a lack of efficacy on Mycoplasma hominis. The efficacy on Treponema pallidum remains to be clinically tested.

Preferential V delta 1 expression among TcR gamma/delta-bearing T cells in human oral epithelium.

The oral cavity is a septic area colonized by various bacterial species, and the oral mucosa is frequently submitted to microtraumas. Several mechanisms are implicated in the defence of the oral tissue, but little is known concerning the eventual presence and role of gamma/delta T cells at this site. Samples of healthy keratinized oral mucosa were examined with immunochemical techniques using anti-CD3, CD4, CD8, CD22, TcR delta 1, V delta 1 and V delta 2 monoclonal antibodies. Whatever the site examined, gamma/delta T cells represent at most 2% of the T-cell population, a value similar to that found in other tissues. In the connective tissue, under the basement membrane, V delta 2+ gamma/delta T cells are predominant whereas the epithelium mostly contains V delta 1+ gamma/delta T cells. The significance of this preferential V delta 1 intraepithelial presence is discussed.

Co-selection of the rare T cell receptor-gamma B haplotype in mouse lines selected for low responsiveness to red blood cell antigens.

T cell receptor (TcR)-gamma haplotype was investigated in seven pairs of murine Biozzi lines selected for low and high antibody (Ab) response to different antigens (Ag). High-responder lines (H) express gamma A or gamma C haplotypes irrespective of the selecting Ag. In contrast, the gamma B haplotype, which is rare in laboratory mouse strains, is found in all low-responder lines (L) to sheep erythrocyte Ag (SE). However, the TcR-gamma B locus might only have a low penetrance in the control of the SE response. Moreover, investigations using LIVA mice, which were selected for low SE response from homozygous gamma A founder parents, indicate that the gamma B haplotype is neither necessary nor sufficient to achieve a low-responder phenotype. The gamma B haplotype might, thus, be co-selected to confer to L mice an improved resistance to bacterial infections mediated by gamma delta T cells compensating the profound and nonspecific immune perturbation associated with the low Ab response.

New T-cell receptor gamma haplotypes in wild mice and evidence for limited Tcrg-V gene polymorphism.

Tcrg gene polymorphism was investigated by Southern blot analysis on a panel of laboratory and wild mouse strains using a set of probes which identify all known Tcrg-V and -C genes. Only three haplotypes are found in laboratory mice: gA, gB, and gC which are represented by BALB/c, AKR, and DBA/2 prototypes respectively. gA and gC haplotypes are the most frequent among laboratory mice whereas gB is poorly represented. Seven new haplotypes are described among 23 wild mice corresponding to four Mus musculus subspecies (Mus mus domesticus, castaneus, musculus, and molossinus). However, only a few new alleles of individual genes are observed. Tcrg-V genes located at the 5' end of the Tcrg locus (V7 and V4) appear to be nonpolymorphic whereas two Tcrg-V3, -V5, -V6, -C4 and three Tcrg-V1, -V2, -C1, -C2, and -C3 specific restriction fragment length polymorphisms are detected. These results indicate a relatively high degree of conservation of Tcrg genes as compared to other members of the immunoglogulin (Ig) gene family and might be related to the specifity and function of gamma delta T cells. Several of the new haplotypes described here result from point mutations in noncoding Tcrg-V or -C gene-flanking regions. Recombinations may have also participated in the evolution of the Tcrg locus. Finally, these new Tcrg haplotypes are unequally distributed among the four M. m. subspecies and support the idea that the gA and gC haplotypes found in laboratory mice are inherited from M. m. domesticus whereas gB might originate from asian subspecies (castaneus, musculus or molossinus).

Sequence conservation of microsatellites between Bos taurus (cattle), Capra hircus (goat) and related species. Examples of use in parentage testing and phylogeny analysis.

A panel of 70 bovine microsatellites was tested for amplification from goat DNA. Forty-three could be successfully amplified by PCR, 20 of which were tested for polymorphism. Three were applied for parentage testing in goat families and their exclusion probability evaluated. Fourteen were cloned and sequenced from goat DNA, and goat and bovine sequences were compared to evaluate interspecific conservation. Correlation between the structure of the dinucleotide repeat and the number of alleles was studied and indicated that interruption(s) in the repeat could explain the difference in the levels of polymorphism between the two species. This study provides a valuable in vivo clue to the mechanism generating polymorphism in microsatellites. Sequence conservation was also observed for several microsatellites with two wild species of Bovidae, Nilgaï (Boselaphus tragocamelus) and Himalayan Tur (Capra cylindricornis), and with one species of Cervidae, the fallow deer (Cervus dama). This study showed that an estimated 40 per cent of the microsatellites isolated from cattle will prove useful to study the caprine genome and to characterize economically important genetic loci in this species. Moreover, bovine microsatellites were shown to constitute very useful tools for the study of genetic diversity of the Artiodactyla.

Interaction of macrolides with alpha dornase during DNA hydrolysis.

Since patients with cystic fibrosis are often treated with alpha dornase to reduce sputum viscosity, and because of preliminary reports of efficacy of long-term low-dose erythromycin therapy in chronic airway diseases, it is likely that alpha dornase and macrolides might be given together in such patients. A possible interaction between these drugs was therefore investigated. Using hyperchromic effect to quantify alpha dornase activity, a time- and dose-dependent inhibitory effect on human DNA hydrolysis has been observed for erythromycin, roxithromycin and azithromycin. Inhibitory doses 50% for alpha dornase were graphically determined. Azithromycin exhibited the strongest inhibitory effect.

Betaxolol: a pilot study of its pharmacological and therapeutic properties in pregnancy.

Twenty two pregnant women with mild to moderate hypertension were treated with betaxolol (10-40 mg/day), a cardioselective beta adrenoceptor blocking agent. The analysis of the changes from the baseline confirmed the antihypertensive effect of the drug with a mean decrease in SBP of 11.8 mm Hg and in DBP of 8.3 mm Hg. A diastolic BP less than 90 mm Hg was obtained in 20 patients after the first day of therapy. Fetal safety, assessed by ultrasonography and cardiotocographic recording was excellent. The 22 mothers gave birth to 23 live born babies (one twin pregnancy). Mean Apgar scores were 8.3 and 9.1 at 1 and 5 min. Only 1 newborn had an Apgar score less than 7. Three newborns suffered from fetal distress and 1 from threat for causes not related to therapy. At 9 months follow-up, all 23 babies were in good health. These data suggest that betaxolol is effective in reducing maternal blood pressure without any deleterious effect on the foetus and the newborn.

Economic analysis of antibiotic regimens used in the treatment pharyngitis: a prospective comparison of azithromycin versus roxithromycin.

The economic impacts in terms of cost and effectiveness (speed of resolution of symptoms) of 3- and 5-day courses of azithromycin and a 10-day course of roxithromycin were compared in a randomized, open study in patients with symptoms suggestive of beta-haemolytic streptococcal pharyngitis. Direct medical costs and absence from work were recorded and symptom scores and compliance were used to assess the effectiveness of therapies. Although no differences between treatment groups in terms of overall clinical response rates were detected 2 and 4 weeks after the start of treatment, more rapid resolution of symptoms was achieved with 3- and 5-day courses of azithromycin than with a 10-day course of roxithromycin. There was also a significant reduction in the time absent from work in the azithromycin treatment groups. The total costs of care over the 4-week evaluation period were lower for the 3- and 5-day azithromycin courses (US$193.60 and US$195.30 respectively) than for roxithromycin (US$202.10). The major cost components were absence from work (58.6%), visits to the physician (15.3%) and utilization of antibiotics (14.9%). Compliance was significantly better (P < 0.01) in patients prescribed azithromycin for 3 and 5 days (58.0% and 42.9% respectively) than in those who received roxithromycin (20.3%) and a significantly longer symptom-free period (P < 0.01) was reported in azithromycin- compared with roxithromycin-treated patients. These findings support the hypothesis that a 3- or 5-day course of azithromycin is as effective as a 10 day course of roxithromycin in the treatment of patients with pharyngitis and is associated with lower costs. Furthermore, azithromycin is associated with faster resolution of symptoms and improved patient compliance.

Members of the novel WC1 gene family are differentially expressed on subsets of bovine CD4-CD8- gamma delta T lymphocytes.

CD4-CD8- gamma delta T cells of ruminants uniquely express a 220-kDa surface Ag recognized by several mAbs clustered as WC1. We recently reported the isolation of a cDNA clone encoding a WC1 Ag. Southern blotting suggested that the bovine genome contains multiple sequences highly related to the isolated WC1 cDNA. Here, we demonstrate that some of the clustered WC1 mAbs stain predominantly nonoverlapping subsets of bovine CD4-CD8- gamma delta T cells. By the isolation of two additional cDNA clones encoding molecules highly related to the original WC1 Ag, we provide a molecular basis for this phenomenon. Cells transfected with cDNAs encoding individual WC1 Ags are differentially recognized by various WC1 mAbs. Thus, expression of members of the WC1 gene family divides bovine CD4-CD8- gamma delta T cells into phenotypical subsets. Field inversion gel electrophoresis revealed that all WC1 genes map to a single, large (> 1 Mbp) Notl fragment. Although the function of WC1 remains unknown, it likely involves interaction with ligands that originate from a similarly complex genetic system.

A microsatellite within the bovine kappa-casein gene reveals a polymorphism correlating strongly with polymorphisms previously described at the protein as well as the DNA level.

The polymorphism of a (TA)n(CA)n repeat microsatellite present in the third intron of the bovine kappa-casein gene (CASK) has been investigated. The existence of six alleles differing only in the number of dinucleotide repeats has been established. A total of 330 animals belonging to nine different pure bred Bos taurus French breeds or to a cross-bred Bos taurus x Bos indicus population (Créole) were genotyped. The distribution of the microsatellite alleles was examined and clear breed differences were noted. Genotyping of animals by isoelectric focusing (IEF) or restriction fragment length polymorphism (RFLP) (TaqI) was performed, in order to examine the relationship of the microsatellite polymorphism to other previously described CASK polymorphisms, at the protein and DNA levels. Strong correlation was seen, indicating that evolution of the various polymorphisms was not independent, and nine CASK haplotypes were observed.