Pharmacogenomic predictor of long-term residual chemotherapy-induced peripheral neuropathy in ovarian cancer survivors: A substudy of the GINECO Vivrovaire study.

BACKGROUND: Chemotherapy (CT) remains a backbone treatment of epithelial ovarian cancer (EOC) inducing persistent peripheral neuropathy (CIPN). Using a dedicated patient-reported outcome tool, this study investigated persistent CIPN and its pharmacogenetic predictors in a cohort of long-term EOC survivors. METHODS: Vivrovaire was a French multicenter cohort of patients with EOC free of disease 3 years after CT completion. Persistent CIPN was assessed using the FACT/GOG-Ntx4 self-questionnaire. The association of homozygous (hom) or heterozygous (het) single nucleotide polymorphisms (SNPs) in selected genes was evaluated. RESULTS: 130 patients were included with a median time from CT completion of 63 [35-180] months. The median CIPN score was 37 [18-44], with 35 (26.9%) patients reporting severe CIPN (<33). SNPs were identified as follows: CYP2C8 [hom, n = 32 (24.6%)/het, n = 99, (76.2%)]; CYP3A4 [hom, n = 0 (0%)/het, n = 8 (6.2%)], ERCC1 [hom, n = 21 (16.2%)/het, n = 57 (43.8%)], and XPC [hom, n = 45 (34.6%)/het, n = 66 (50.8%)]. In univariate analysis, the identification of ≥1 hom SNP was associated with a lower CIPN score (continuous variable; p = 0.045). Patients harboring hom or het CYP2C8_rs1934951 SNP reported more likely severe CIPN (threshold <33) score (OR 2.482; 95% CI [1.126-5.47], p = 0.024). In the multivariate analyses, age, interval from CT completion, type and number of CT courses were not significantly associated with CIPN score (OR 5.165, 95% CI [0.478-55.83], p = 0.176). CONCLUSIONS: Persistent CIPN is common among ovarian cancer long-term survivors. CYP2C8_rs1934951 SNP may be associated with severe residual CIPN in EOC survivors. More studies are warranted to identify predictive factors of CIPN.

Effect of the order of incorporation of cake ingredients on the formation of batter and the final properties: contribution of the addition of pea flour.

The investigation dealt with the effect of the replacement of a part of wheat flour by pea flour on the properties of batters and cakes. As the protein composition of pea flour differs from that of wheat, the effect of its incorporation on batter formation and cake properties was monitored throughout the different steps of cake processing. The incorporation of air, which influences the cell structure and density of the cake, was the subject of particular attention. Four orders of incorporation were first investigated to identify their effects on a standard recipe made with 100% wheat flour. Mixing first egg and sugar together allows introducing air, but most of it is lost after oil and flour introduction. Whatever the order of incorporation, the density of the batter ends around 1.1 ± 0.2 g.cm-1. However, batter consistencies are significantly different and resulting cakes show different crumb structures. These results are discussed in terms of physicochemical mechanisms, and a schematic representation of the phenomena occurring at the different steps of mixing depending on the order of ingredient incorporation is proposed. When 20 and 40% of the wheat flour was replaced by pea flour using the two most energy-efficient orders of incorporation, more air was incorporated into the batter. However, the resulting cakes were denser, but surprisingly softer. Differences in cell structure explain this apparent contradiction.

Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease.

BACKGROUND: Crohn's disease (CD)-associated dysbiosis is characterised by a loss of Faecalibacterium prausnitzii, whose culture supernatant exerts an anti-inflammatory effect both in vitro and in vivo. However, the chemical nature of the anti-inflammatory compounds has not yet been determined. METHODS: Peptidomic analysis using mass spectrometry was applied to F. prausnitzii supernatant. Anti-inflammatory effects of identified peptides were tested in vitro directly on intestinal epithelial cell lines and on cell lines transfected with a plasmid construction coding for the candidate protein encompassing these peptides. In vivo, the cDNA of the candidate protein was delivered to the gut by recombinant lactic acid bacteria to prevent dinitrobenzene sulfonic acid (DNBS)-colitis in mice. RESULTS: The seven peptides, identified in the F. prausnitzii culture supernatants, derived from a single microbial anti-inflammatory molecule (MAM), a protein of 15 kDa, and comprising 53% of non-polar residues. This last feature prevented the direct characterisation of the putative anti-inflammatory activity of MAM-derived peptides. Transfection of MAM cDNA in epithelial cells led to a significant decrease in the activation of the nuclear factor (NF)-κB pathway with a dose-dependent effect. Finally, the use of a food-grade bacterium, Lactococcus lactis, delivering a plasmid encoding MAM was able to alleviate DNBS-induced colitis in mice. CONCLUSIONS: A 15 kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-κB pathway in intestinal epithelial cells and to prevent colitis in an animal model.

Display of recombinant proteins at the surface of lactic acid bacteria: strategies and applications.

Lactic acid bacteria (LAB) are promising vectors of choice to deliver active molecules to mucosal tissues. They are recognized as safe by the World Health Organization and some strains have probiotic properties. The wide range of potential applications of LAB-driven mucosal delivery includes control of inflammatory bowel disease, vaccine delivery, and management of auto-immune diseases. Because of this potential, strategies for the display of proteins at the surface of LAB are gaining interest. To display a protein at the surface of LAB, a signal peptide and an anchor domain are necessary. The recombinant protein can be attached to the membrane layer, using a transmembrane anchor or a lipoprotein-anchor, or to the cell wall, by a covalent link using sortase mediated anchoring via the LPXTG motif, or by non-covalent liaisons employing binding domains such as LysM or WxL. Both the stability and functionality of the displayed proteins will be affected by the kind of anchor used. The most commonly surfaced exposed recombinant proteins produced in LAB are antigens and antibodies and the most commonly used LAB are lactococci and lactobacilli. Although it is not necessarily so that surface-display is the preferred localization in all cases, it has been shown that for certain applications, such as delivery of the human papillomavirus E7 antigen, surface-display elicits better biological responses, compared to cytosolic expression or secretion. Recent developments include the display of peptides and proteins targeting host cell receptors, for the purpose of enhancing the interactions between LAB and host. Surface-display technologies have other potential applications, such as degradation of biomass, which is of importance for some potential industrial applications of LAB.

Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial.

AIM: This study aimed to gain a better understanding of the psychological impact of participating in a clinical trial for patients with Pompe disease (Acid Maltase Deficiency). Attitudes and expectations of adult patients with neuromuscular diseases regarding medical trials are as yet unreported. In order to learn about the psychological consequences of participating in a clinical trial, we conducted a prospective assessment of patients with late-onset Pompe Disease, a rare genetic condition, for which no treatment had been available before. This psychological study was carried out as an ancillary study to the randomized double-blind placebo-controlled trial described elsewhere (van der Ploeg et al., 2010). SUBJECTS AND METHODS: We assessed patients (n=8) at inclusion, and at 12 and 18 months for six psychological dimensions: depression (Beck Depression Inventory, BDI), hopelessness (Beck Hopelessness Scale, BHS), anxiety (STAI A-B), quality of life (Whoqol-26), social adjustment (S.A.S-self-report) and locus of control (IPC Levenson). We produced a self-administered questionnaire in order to assess the attitudes, motivations and expectations of patients during the trial. RESULTS: At 12 months, mean social adjustment (SAS-SR, P=0.02) had improved, and at 18 months mean depression score had improved as well (BDI, P=0.03). The quality of life of patients (Whoqol-26) remained unchanged. Throughout the study, patients were more likely to have an internal locus of control than an external one (IPC Levenson). The self-administered questionnaire showed that patients' expectations were disproportionate compared to the medical information they had received starting the trial. For all patients, the first motivation for being enrolled in a clinical trial was "to help research", for half of them the motivation was to "improve their health". Whether patients believed to be part of one group or another (placebo or treatment) depended on their subjective perception of improvement during the trial. CONCLUSION: Given the small sample size, the conclusions of this study are preliminary. However, findings do suggest that there is a positive psychological impact of participating in a treatment trial. Moreover, the patients' reactions upon unblinding have led us to recommend that patients be asked whether they would like their group assignation disclosed to them or not.

Aphasia in border-zone infarcts has a specific initial pattern and good long-term prognosis.

BACKGROUND: While border-zone infarcts (BZI) account for about 10% of strokes, studies on related aphasia are infrequent. The aim of this work was to redefine specifically their early clinical pattern and evolution. METHODS: We prospectively studied consecutive patients referred to our stroke unit within a 2-year period. Cases of aphasia in right-handed patients associated with a MRI confirmed left-sided hemispheric BZI were included. These patients had a standardized language examination in the first 48 h, at discharge from stroke unit and between 6 and 18 months later. RESULTS: Eight patients were included. Three had anterior (MCA/ACA), two posterior (MCA/PCA), two both anterior and posterior, and one bilateral BZI. All our patients initially presented transcortical mixed aphasia, characterized by comprehension and naming difficulties associated with preserved repetition. In all patients, aphasia rapidly improved. It fully recovered within a few days in three patients. Initial improvement was marked, although incomplete in the five remaining patients: their aphasias specifically evolved according to the stroke location toward transcortical motor aphasia for the three patients with anterior BZI and transcortical sensory aphasia for the two patients with posterior BZI. All patients made a full language recovery within 18 months after stroke. CONCLUSIONS: We report a specific aphasic pattern associated with hemispheric BZI, including an excellent long-term outcome. These findings appear relevant to (i) clinically suspect BZI and (ii) plan rehabilitation and inform the patient and his family of likelihood of full language recovery.

Arsenic mass balance in a paper mill and impact of the arsenic release from the WWTP effluent on the Moselle River.

Rivers used for drinking water production might be subject to anthropogenic pollution discharge upstream of the intake point. This problem was investigated in the case of the Moselle River, used for water production in Nancy (350,000 inhabitants) and which might be impacted by industrial activities 60 km upstream. The arsenic flux of a pulp and paper mill discharging in the Moselle River at this location has been more specifically investigated. The main sources of arsenic in that mill seemed to be the recovered papers and the gravel pit water used as feed water. The arsenic input related to wood and bark was limited. The main arsenic outputs from the plant were the paper produced on site and the deinking sludge. The arsenic concentration in the effluent of the wastewater treatment plant (WWTP) was not correlated to the one in the gravel pit water, but may depend on the operating conditions of the WWTP or the changes in processes of the mill. The impact of this anthropogenic source of arsenic on the Moselle River was slightly larger in summer, when the flowrate was lower. Globally the impact of the paper mill on the Moselle River water quality was limited in terms of arsenic.

Pickering emulsions based on food byproducts: A comprehensive study of soluble and insoluble contents.

HYPOTHESIS: Pickering emulsions can be produced using raw particles obtained from uncracked vegetal food byproducts as sole stabilizers. The complexity brought by these non-purified ingredients will be their strength since insoluble particles and soluble compounds shall display good complementary properties, at the interface and the continuous phase. EXPERIMENTS: Emulsions were monitored over a one-month storage as regards to oil droplet diameter as main indicator of stability. Then, two main studies were carried out: 1) on the whole powders (water binding capacity, dry matter and insoluble content, size and morphology); 2) on the soluble content (size, charge, pH, Brix degree, surface tension measurements). FINDINGS: All byproducts stabilized-emulsions were stable during storage. They display various oil droplet sizes with sugar beet < apple < oat. Direct observation of the oil-water interfaces showed adsorption of the solid particles, and some voids corresponding to soluble elements from the byproducts' powders. The latter displayed surface-active properties. The insoluble particles are driving the oil droplet size and protecting against coalescence while soluble compounds can also adsorb at the interface, lowering droplet size, and also act as thickening agents from the continuous phase (pectins). Vegetal byproducts are thus meta ingredients, able to stabilize clean-label emulsions.

Potential of model cakes to study reaction kinetics through the dynamic on-line extraction of volatile markers and TD-GC-MS analysis.

This study presents a novel strategy for the dynamic analysis of volatile compounds extracted from baking vapors using a fit-for-purpose model cake. This model imitates a real sponge cake in terms of structure and processing but it is not reactive towards Maillard and caramelization reactions. When implemented with precursors (glucose (G) or glucose + leucine (G + L)), the reactions are activated and volatile markers can be monitored dynamically during baking. A method for the on-line sampling of vapors during baking using sorbent tubes coupled to thermal desorption (TD-GC-MS) has been developed and proven to be an appropriate and rapid technique to analyze a large number of volatile compounds within a broad range of physical and chemical characteristics. Volatile markers such as acetic acid, furfural, furfuryl alcohol and 5-hydroxymethylfurfual were identified using both models: glucose (G) and glucose + leucine (G + L) because they arise from both caramelization and the Maillard reaction. On the other hand, 3-methylbutanal and 2,5-dimethylpyrazine were only identified in the (G + L) model cake as they arise from the Strecker degradation pathway induced by the presence of leucine. Moreover, the relative abundance of all markers of reactions covers a broad range. On-line sampling coupled to TD-GC-MS enabled the collection of kinetic data on these markers throughout the baking operation and discrimination of the two formulas (G vs G + L) and two baking temperatures (170 °C and 200 °C) used. These results offer promise for the further use of this approach to study reaction kinetics in model cakes.

Gastro-intestinal in vitro digestions of protein emulsions monitored by pH-stat: Influence of structural properties and interplay between proteolysis and lipolysis.

This study describes an experimental design, based on pH-stat, to rapidly screen and assess food formulation effects on the degrees of hydrolysis (DH) of both proteins and lipids throughout in vitro gastro-intestinal digestions. This approach was used to quantitatively compare and hierarchize key structure parameters of protein emulsions. Six matrices (15 wt% whey proteins, 0 or 10 wt% oil), each differing by at least one structure characteristic, were studied. The physical state of the bulk and the oil droplet size were the major structural levers to modulate the hydrolysis of proteins (final DH between 51.7 and 58.3%) and lipids (final DH between 46.9 and 72.7%), with non-trivial interplays between proteolysis and lipolysis. Additionally, pH-stat measurements in presence of a pancreatic lipase inhibitor proved to be an efficient way to widen the scope of the proposed experimental approach to foods that are intrinsically made of both proteins and lipids.

Secondary findings from next generation sequencing: Psychological and ethical issues. Family and patient perspectives.

Access to active search for actionable secondary findings (SF) in diagnostic practice is a major psychological and ethical issue for genomic medicine. In this study, we analyzed the preferences of patients and their families regarding SF and identified the reporting procedures necessary for informed consent. We interviewed parents of patients with undiagnosed rare diseases potentially eligible for exome sequencing and patients affected by the diseases listed in the ACMG recommendations. Four focus groups (FG) were formed: parents of patients with undiagnosed rare diseases (FG1, n = 5); patients with hereditary cancers (FG2, n = 10); patients with hereditary cardiac conditions (FG3, n = 3); and patients with metabolic diseases (FG4, n = 3). Psychologists presented three broad topics for discussion: 1. Favorable or not to SF access, 2. Reporting procedures, 3. Equity of access. Discussions were recorded and analyzed using simplified Grounded Theory. Overall, 8 participants declared being favorable to SF because of the medical benefit (mainly FG1); 11 were unfavorable because of the psychological consequences (mainly FG2, FG3, FG4); 2 were ambivalent. The possibility of looking for SF in minors was debated. The 4 key information-based issues for participants ranked as follows: explanation of SF issues, autonomy of choice, importance of a reflection period, and quality of interactions between patients and professionals. Examining equity of access to SF led to philosophical discussions on quality of life. In conclusion, individual experience and life context (circumstances) were decisive in participants' expectations and fears regarding access to SF. Additional longitudinal studies based on actual SF disclosure announcements are needed to establish future guidelines.

Confocal scanning laser microscopy and quantitative image analysis: application to cream cheese microstructure investigation.

The naked eye observation of cream cheese confocal scanning laser microscopy images only provides qualitative information about its microstructure. Because those products are dense dairy gels, confocal scanning laser microscopy images of 2 different cream cheeses may appear close. Quantitative image analysis is then necessary to compensate for human eye deficiency (e.g., lack of precision, subjectivity). Two kinds of quantitative image analysis were performed in this study: high-order statistical methods and grayscale mathematical morphology. They were applied to study the microstructure of 3 different cream cheeses (same manufacturing process, same dry matter content, but different fat and protein contents). Advantages and drawbacks of both methods are reviewed. The way they may be used to describe cream cheese microstructure is also presented.

In vitro digestion of short-dough biscuits enriched in proteins and/or fibres using a multi-compartmental and dynamic system (2): Protein and starch hydrolyses.

The influence of protein and/or fibre enrichment on the nutritional properties of biscuits was studied in terms of proteolysis and amylolysis. Biscuits were digested using a multi-compartmental and dynamic system that simulates the main physiological digestive functions of the upper tract of healthy adult humans: the TIM-1. A control biscuit and three biscuits enriched in proteins and/or fibres were digested under the same conditions. Samples were collected in each compartment of the TIM-1 (stomach, duodenum, jejunum and ileum) at different times of digestion and analysed in terms of proteolysis and amylolysis. Results indicate that both formulation and processing impacted the digestive fate of the biscuits. Incorporating proteins or fibres in biscuits lowered or delayed proteolysis. Moreover a protein-plus-fibre additional or synergic effect was observed. Biscuits enriched in proteins and/or fibres displayed a higher amylolysis degree than the control biscuit, probably due to lower starch amounts and higher gelatinization degrees.

In vitro digestion of short-dough biscuits enriched in proteins and/or fibres, using a multi-compartmental and dynamic system (1): viscosity measurement and prediction.

The effects of biscuit composition on the viscosity generated during digestion were investigated. A control biscuit, one with proteins, one with fibres, and one with both proteins and fibres were digested under the same conditions, using the TNO intestinal model (TIM-1). The TIM-1 is a multi-compartmental and dynamic in vitro system, simulating digestion in the upper tract (stomach and small intestine) of healthy adult humans. Digesta were collected at different times, in the different compartments of the TIM-1 (stomach, duodenum, jejunum and ileum) and viscosity was measured with a dynamic rheometer. Results showed a marked effect of biscuit composition on chyme viscosity. Highest viscosity was obtained with biscuits containing viscous soluble fibres, followed by those enriched in both proteins and fibres, then by protein-enriched and control biscuits. The viscosity was maintained throughout the gut up to the ileal compartment. A prediction of the evolution of the chyme viscosity in each compartment of the TIM-1 was built, based on model curves describing the evolution of the viscosity as a function of biscuit concentration, and on dilution factors measured by spectrophotometry on a blank digestion.

Determinants of delayed diagnosis of HIV infection in France, 1993-1995.

OBJECTIVE: To describe the circumstances of the first HIV-positive test and to study the determinants of a delayed diagnosis of HIV infection. METHODS: In a retrospective study among adult AIDS patients diagnosed between July 1993 and May 1995 in two French districts, data on socioeconomic characteristics, circumstances of first HIV-positive test and attitudes and behaviours regarding medical care were collected in a confidential interview and analysed for potential association with a late test, defined as a first HIV-positive test within 6 months of AIDS diagnosis. RESULTS: Of the 359 AIDS patients studied, 69 (19.2%) had a late test. Late testers were more likely than other patients to have had an HIV-positive test because of clinical symptoms (89.7 versus 38.9%, P < 0.001) and not to perceive themselves as being at risk of infection with HIV (53.6 versus 39.3%, P < 0.05). The proportion of late testers was 34.6% among heterosexually infected patients, 12.7% among homo-/ bisexual men and 9.6% among injecting drug users. Factors independently associated with a late test were male gender [adjusted odds ratio (aOR), 5.6; 95% confidence interval (CI), 1.7-18.9] and absence of earned income (aOR, 5.2; 95% CI, 1.4-19) among heterosexually infected patients; high education (aOR, 3.1; 95% CI, 1.0-9.6) and having consulted a person practising alternative medicine (aOR, 3.4; 95% CI, 1.2-10) in homo-/bisexual men. CONCLUSIONS: Despite incentives to be tested for HIV, many individuals in France are still tested too late, even if they are in known high-risk groups. Efforts to test HIV-infected people as early as possible should be made by increasing the perception of HIV risk and decreasing the level of missed opportunities for testing. Current case management approaches make this recommendation critically important from both public health and an individual perspective.

Chiral "metallo-spiralenes": helical molecules conformationally stabilised by an organometallic scaffold

The synthesis of a series of chiral cyclomanganated 2-[(eta 6-phenyl)-Cr(CO)3]pyridine complexes derived from (-)-beta-pinene enables, by a "spirogenic transformation", the preparation of four different chiral helical heterobimetallic syn-facial complexes or Cr0/Mn1-spiralenes, among which two possess a right-handed P molecular helicity and two other a left-handed M one. These organometallic helical molecules are synthesised by applying two different methods to the chiral cyclomanganated (eta 6-arene)tricarbonylchromium substrates. The first method is the so-called "Fischer route" which involves a sequential addition of PhLi and MeOTf. The second method based on reaction of the cyclomanganated complex with diphenyldiazomethane which has been tested on achiral bimetallic substrates is a reasonable neutral alternative to the "Fischer methodology" for the synthesis of Cr0/Mn1-spiralenes. The crystal structure of one of these heterobimetallic chiral helical compounds serves as a starting point in the configurational and structural assessment of the synthesised chiral (eta 6-arene)tricarbonylchromium complexes. Application of the "Fischer route" to a cyclomanganated chiral 2-phenylpyridine generates a single chiral eta 3-benzylic complex--or Mn1-spiralene--bearing a left-handed M helicity which has been characterized by X-ray diffraction analysis. Circular dichroic spectroscopic measurements underline the predominant contribution of the chiral and chirally induced aromatic chromophores to the sign of the Cotton effects and confirm the helical configurations of the considered heterobimetallic species.

Influence of thermal history on the stability of gelatin gels.

Gelatin gel properties have been studied using three techniques. Optical rotation measurements have shown that the lower the ageing temperature, the faster the helix content increases but the lower the helix stability. Rheological measurements show that a small increase in temperature leads to a melting of some junction zones followed by a build up of new ones. By ageing the gel at two successive temperatures one can show the existence of two populations of junction zones with different thermal stabilities. The same result is shown on melting thermograms obtained by differential scanning calorimetry. All these results are consistent with the hypothesis of the presence of junction zones of various lengths, the thermostability of which being proportional to their lengths.

Central corneal dermoid: a clinicopathologic correlation and review of the literature.

The authors present a clinicopathologic correlation of a central corneal dermoid removed from a one-year-old child. Contrary to the initial clinical impression, the tumour involved the full thickness of the corneal stroma, necessitating a penetrating keratoplasty. After the graft became opaque, a second penetrating keratoplasty was required. In spite of the fact that the eye has remained amblyopic, its cosmetic appearance is excellent. Problems related to the management of central corneal dermoids are discussed.

[Factors associated with medical management of HIV infected persons in two French districts, 1993-1995]. / Facteurs associés à la prise en charge médicale des personnes infectées par le VIH dans deux départements français, 1993-1995.

BACKGROUND: The regularity of medical followup of HIVinfected patients greatly influences the effectiveness of antiretroviral treatments and of prophylaxis of opportunistic infections. METHODS: To identify potential barriers to a regular followup, a retrospective study was conducted among the adult AIDS patients diagnosed between July 1993 and May 1995 in two French districts (Gironde and HautsdeSeine). Medical followup was described based on the frequency of CD4 counts in the medical file and on a confidential interview among patients whose HIV infection had been diagnosed at least 6 months before AIDS. Irregular followup (less than one CD4 count per year when CD4> 500/ mm(3), and per 6months when CD4< 500/ mm(3)) within the two years preceding AIDS diagnosis was analysed according to socioeconomic status and to social and behavioral factors. RESULTS: Among 290 patients, followup was irregular in 51% of the patients (injecting drug users: 66%, homo/bisexual men: 41%, patients infected through heterosexual contact: 49%, p<0.01). Factors independently associated with irregular followup were low income level (adjusted odds ratio (aOR)= 2.4; 95% confidence interval (CI), 1.44.1); absence of regular practitioner at HIV diagnosis (aOR= 1.9; 95% CI 1.13.3); imprisonment between HIV diagnosis and AIDS (aOR= 3.8; 95% CI 1.310. 9), and being non homo/bisexual male (aOR= 2.4; 95% CI 1.15.1) versus homo/bisexual male (aOR= 1.3; 95% CI 0.72.7) and female (reference). CONCLUSIONS: Results of this study show that several socioeconomic, psychological and cultural barriers to a regular preAIDS medical followup still exist. Impact of new antiretroviral therapy may only be optimal if these barriers are overcome.

[Hepatic, biliary and pancreatic lesions in LAV-HTLV III infection]. / Les lésions hépatiques, biliaires et pancréatiques au cours de l'infection par LAV-HTLVIII.

We believe it is important to underscore: The frequency and variety of the lesions, mainly within the liver but also of the biliary tract and the pancreas, which may reveal an inaugural complication of AIDS. The interest of the vascular lesions, mainly of the sinusoids as well as the various associated lesions due to pathogens (bacteria, viruses, fungi) and/or to toxic drugs. The physiopathology and histogenesis of the lesions are still obscure. Both the lesions of the hepatocytes and these of the sinusoids are poorly understood, and it is reasonable to discuss the role of various pathogens, such as viruses, peculiarly Epstein Barr and moreover LAV-HTLVIII viruses.