Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients presenting gastrointestinal disorders: a pilot study.

Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of this prospective study was to evaluate the effect of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in liver transplant patients presenting GI side-effects Since January 2003, stable liver transplant patients receiving MMF and presenting GI disorders, without evidence of other origin than MMF were enrolled. Conversion was performed without a washout period at an equimolar daily dosage. Thirty-six patients were included after a median delay of 45 months after liver transplantation (LT) (16 women and 20 men, median age of 47 years). Diarrhoea was the main clinical symptom (n = 28, 77.7%). At the time of inclusion, patients were treated with MMF since 18 months (range 3-28) and GI disorders were known for 9 months (range 3-12). After a median follow-up of 12 months after conversion, GI disorders were resolved in 20 patients (55%), improved in 6 patients (17%) and not modified or worsened in 10 patients (28%). Our results strongly suggest that conversion from MMF to EC-MPS in liver transplant patients can improve gastrointestinal disorders in a majority of the patients, and therefore might be considered as the best therapeutic option.     

Analysis of human growth hormone-binding protein in plasma by high pressure liquid chromatography]

A technique using high pressure liquid chromatography gel filtration was used to evaluate GH-binding proteins (GH-BPs) in human plasma; eluate was monitored for radioactivity in a gamma-detection system connected to a computer. Plasma (200 microliters) was incubated with 125I-human (h) GH (200,000 cpm) at 4 degrees C for 20 hours. Our GH binding assay offers important gains in terms of rapidity and resolution; it has permitted a clear separation and characterization of the two GH-binding components present in human plasma.     

Infected chronic hematoma mimicking soft tissue neoplasm

A rare case of an infected chronic hematoma in a patient with immunodeficiency syndrome mimicking a soft tissue neoplasm is presented. There are few reported cases of hematogenous infection of chronic hematomas, which be difficult to differentiate from soft tissue neoplasms.     

Global molecular epidemiology of the O15:K52:H1 extraintestinal pathogenic Escherichia coli clonal group: evidence of distribution beyond Europe

Escherichia coli O15:K52:H1 is a significant extraintestinal pathogen in Europe (G. Prats et al., J. Clin. Microbiol. 38:201-209, 2000). To search for evidence of this clonal group outside of Europe, 75 non-European E. coli isolates of serogroup O15 were compared with five members of the O15:K52:H1 clonal group from Barcelona, Spain, according to genomic background, virulence genotypes, and antimicrobial resistance profiles. Amplification phylotyping showed that 16 (21%) of the 75 non-European O15 isolates corresponded with the O15:K52:H1 clonal group. The 16 non-European O15:K52:H1 clonal group members represented diverse geographic locales. They were isolated almost exclusively from humans with extraintestinal infections and accounted for 50% of all O15 isolates from five human clinical collections studied. Most non-European clonal group members exhibited a consensus virulence factor profile that included the F16 or F7-2 papA alleles (P fimbrial structural subunit), papG allele II (P fimbrial adhesin), iha (putative adhesin siderophore), and iutA (aerobactin receptor). This resembles the virulence profiles of (i) European representatives of the O15:K52:H1 clonal group and (ii) phylogenetically related "clonal group A," a recently recognized significant contributor to trimethoprim-sulfamethoxazole resistance in the United States (A. R. Manges et al., N. Engl. J. Med. 345:1007-1013, 2001). Antimicrobial resistance profiles were variable, and resistance was inconsistently transferred by conjugation. These findings indicate that the O15:K52:H1 clonal group is broadly distributed beyond Europe, exhibits previously unrecognized phenotypic and genotypic diversity, and contributes significantly to extraintestinal infections in humans.     

Interleukin-1 release by alveolar macrophages in asthmatic patients and healthy subjects

A thymocyte proliferative response assay was used to compare spontaneous and lipopolysaccharide (LPS)-induced interleukin-1 (IL-1) release by alveolar macrophage (AM) in asthmatic patients and normal subjects. Twelve asthmatic patients and seven nonsmoking healthy subjects underwent a bronchoalveolar lavage (BAL). All asthmatic patients had a reversible airway obstruction and 7/12 were allergic. BAL AM were separated by adherence on tissue culture plates in medium RPMI-1640 supplemented with antibiotics and fetal calf serum, and were incubated with or without 10 micrograms/ml LPS for 20 h. Free-cell supernatants were tested by C3H/HeJ mice thymocyte proliferative assay. Unstimulated AM supernatant IL-1 activity was significantly higher in asthmatic patients (mean +/- SEM: 47.8 +/- 11.9 units/10(6) AM) in comparison with healthy subjects (4.8 +/- 2.3 units/10(6) AM; p less than 0.05, Mann-Whitney U test) but did not significantly differ between allergic (42.2 +/- 15.5 units/10(6) AM) and intrinsic asthmatic patients (55.8 +/- 20.7 units/10(6) AM). For healthy subjects, IL-1 activity was significantly higher in LPS-stimulated AM supernatants (85 +/- 20 units/10(6) AM, p less than 0.05; Mann-Whitney U test) in comparison with unstimulated ones; for asthmatic patients, unstimulated and LPS-stimulated AM supernatant IL-1 activity did not significantly differ. This finding is in accordance with previous work suggesting that AM from asthmatic patients have a weak suppressive activity upon lymphocyte proliferation and emphasize the enhanced AM releasability in asthma.     

Detection of antigen receptor gene rearrangements in lymphoproliferative malignancies by fluorescent polymerase chain reaction

Abstract: Monoclonal rearrangements of antigen receptor genes in lymphoproliferative diseases are characterized by the specific sequence and the length of their junctional region, which can be used as markers of the proliferating clone. PCR techniques have greatly simplified routine detection of monoclonal rearrangements. But on the one hand, identification of the sequences requires sequencing methods and on the other hand, sizing of rearrangements by conventional analysis of PCR products on agarose or nondenaturing polyacrylamide gels may be uncertain. We have developed an approach based on amplification of rearranged IGH, TCRG and TCRD locus by fluorescent PCR associated to a computerized analysis of generated PCR products allowing their objective sizing. We tested this method on DNA samples from patients with acute lymphoblastic leukemia and chronic lymphocytic leukemia, whose pattern of IGH and TCRG rearrangements had been previously identified by Southern blot techniques. TCRG-PCR assay allowed detection of 100% of rearranged samples. No false-negative results were found but a high rate (60%) of Southern-negative and PCR-positive samples were identified. TCRD PCR-assay detected VD1JD1 or VD2-D2/3 rearrangements in both acute lymphoblastic leukemia and chronic lymphocytic leukemia samples. IGH PCR assay permitted detection of all known rearranged samples. The sensitivity of these three different PCR assays (1% leukemic cells) was equivalent to that of other published PCR protocols. These results show the validity and reliability of the fluorescent PCR method for routine detection of IGH, TCRG and TCRD rearrangements. Sizing of PCR products by computerized analysis was also validated. It provides additional information on rearrangement patterns in lymphoproliferative diseases, as clonal rearrangements can be recognized by their size. This can be of great interest in various circumstances, particularly for detection and follow-up of oligoclonality.     

Etude microscopique de transplantations hepatiques allogeniques chez le porc

Résumé Dix transplantations hépatiques allogéniques effectuées chez le porc et suivies de survies oscillant entre 24 heures et plusieurs mois, ont permis l'étude des variations histomorphologiques du greffon dans le temps. Hormis le risque initial de nécrose massive du transplant (3 animaux décédés en 24 à 48 heures), la réaction de rejet aigu, ébauchée dès le 3ème jour, atteint toute son ampleur au 7ème jour. Comme dans d'autres viscères (rein et coeur notamment) elle se traduit par une prolifération de cellules mononucléées (lymphocytes, cellules blastoïdes) dans les vaisseaux puis dans le mésenchyme adjacent. Mais elle est habituellement très modérée, n'ayant déterminé qu'une seule fois une véritable hépatite inflammatoire massive et nécrosante. De surcroit, chez les animaux ayant survécu plus longtemps (1 mois à 5 mois et demi), il est frappant de constater que cette réaction de rejet initiale tend à se stabiliser, voire même à disparaitre: au granulome actif portal succède une sclérose cicatricielle favorisant sans doute par son retentissement sur les canaux biliaires la survenue d'infections hépato-biliaires très fréquentes durant cette période. Dans un cas même, il ne persistait que de minces bandes de sclérose inflammatoire délimitant des lobules hépatiques très volumineux.En somme, aux réactions immunologiques antagonistes provoquées initialement par la transplantation, semble succéder, chez le porc, un véritable état de tolérance s'accompagnantmême parfois d'une hypertrophie compensatrice du greffon.

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Microscopic study of liver orthotopic transplantation in the pig

Summary Ten orthotopic allogenic transplantations of porcine liver survived from 24 hours to several months permitting the study of histomorphological variations of the graft. Beside the initial risk of massive liver necrosis (three animals died within 24–40 hours), the acute rejection that began early (third day) reached maximum intensity at the end of the first week. As in other kinds of transplantation (kidney, heart) the rejection was characterized by the presence of mononuclear cells (lymphocytes, blastoid cells) in the small vessels and adjacent mesenchyma. This reaction was generally moderate; we observed just once a really massive inflammatory hepatitis.In the animals which survived from one five and a half months, it was surprising to note that the initial rejection-reaction tended to disappear: the portal granuloma was replaced by sclerosis about biliary vessels; this sclerosis might be a possible cause of hepatobiliary infection frequently observed during this period.In one animal only very thin strips of inflammatory sclerosis persisted delimiting large hepatic lobules.In conclusion, we believe that in the particular case of porcine liver the initial reaction of rejection is followed by a real tolerance and from time to time by a compensatory hypertrophy of the graft.

     

Nutrition in the prevention of neoplastic disease in the elderly

This review focuses on specific effects of diet on cancer risk and the relevance of these dietary effects to the risk of cancer in the elderly. The authors address the impact of certain dietary factors on cancer risk by reviewing their roles in two distinct phases of carcinogenesis: "imitation" and "promotion."