Juvenile Idiopathic Arthritis

Overexpression of cytokines in inflamed joints plays an important role in joint inflammation and in damage to articular tissue. Biological agents aimed at specifically antagonising tumour necrosis factor (TNF) are effective in the treatment of adult rheumatoid arthritis. A recent trial of etanercept, a genetically engineered fusion protein consisting of the Fc domain of human IgG1 and the TNF receptor p75, has demonstrated that this agent is also well tolerated and effective in patients with juvenile idiopathic arthritis (JIA). Etanercept offers a promising new alternative for patients with JIA who have persistently active arthritis despite treatment with methotrexate. Further studies are needed to clarify whether etanercept is equally effective in the various onset types of JIA (oligoarthritis, polyarthritis and systemic arthritis), whether it can modify disease progression and whether it can be administered safely for long periods of time to children.     

Determination of rate-constants as a method to describe passive expiration

To describe the relaxed expiration by a two-compartment model, we introduced a gas/energy transfer between the lung compartment (V₁) and a second one (V₂). If V₂ were a real volume, the rate-constants (i.e. the flow/volume ratios) of the compartments would describe a real gas-exchange. Alternatively, if a viscoelastic behaviour of the lung or an energy-exchange between compartments was simulated, V₂ would become a "pseudo-volume". We studied nine mechanically ventilated subjects. Changes in volume were transduced by respiratory inductive plethysmography. The rate-constants were assumed (together with the initial volumes of the compartments) as parameters to fit the total volume [V₁(t)+V₂(t)]. Once the best fitting was performed using these "physiological" parameters, the system was directly identified and the compartments were independently analysed. The time profile of the second compartment showed a maximum that depended on the value of the rate-constants. Appropriate tests confirmed the reliability of our procedure. In conclusion, our analysis demonstrated that the energy/volume of the second compartment may increase at the beginning of expiration and then decrease, showing a maximum, even though the total curve can only be a decreasing one. In other words, the slowing down of the curve representing expiratory volume is due not only to the longer emptying of the second compartment, but also to the interaction between the two compartments. As presently proposed, this interaction can be represented by either a gas exchange between two actual volumes, or a mechanical energy transfer between the lung and the tissue compartment.     

Relationships between total plasma load of torquetenovirus (TTV) and TTV genogroups carried

In 239 torquetenovirus-positive people, multiple-genogroup infections were common and associated with higher viral loads than would be expected from simple additive effects. The latter observation was restricted to the infections which included both genogroups 1 and 3, pointing to the possible existence of some kind of infection facilitation between these genogroups.     

Neutralizing and binding antibodies to IFN-beta: relative frequency in relapsing-remitting multiple sclerosis patients treated with different IFN-beta preparations.

The frequencies of anti-interferon-beta (IFN-beta) antibody development reported to date in patients treated with different IFN-beta preparations are not readily comparable mainly because of differences in underlying diseases and assay methods. Thus, the frequency of neutralizing antibody (NAb) and binding antibody (BAb) development was analyzed in a sample of sera derived from a homogeneous group of relapsing-remitting multiple sclerosis (RRMS) patients treated with different IFN-beta preparations. The frequency of developing NAb and BAb to IFN-beta varied according to the IFN-beta given. Specifically, the NAb seroconversion frequency was significantly higher in patients treated with Betaferon, Schering AG, Berlin, Germany (31.3%) than in patients treated with both preparations of recombinant IFN-beta 1a (Rebif, Serono, Geneva, Switzerland [7.4%] or Avonex, Biogen, Cambridge, MA [6.3%]). Analysis of BAb seroconversion frequency in the same patients revealed that different IFN-beta preparations may also have different capability to induce BAb development and that BAb are produced during IFN-beta therapy at a significantly higher rate than NAb. Our main conclusion is that different human IFN-beta preparations may possess different immunogenicities, leading to varying frequency of development of antibody to IFN-beta in RRMS.     

Cryptosporidium parvum-specific CD4 Th1 cells from sensitized donors responding to both fractionated and recombinant antigenic proteins

T-cell-mediated immunity plays a central role in the host response to Cryptosporidium parvum. Human T-cell clones (TCC) were isolated from peripheral blood mononuclear cells of five healthy donors with prior cryptosporidiosis by use of a C. parvum crude extract, two antigen fractions obtained by ion-exchange chromatography (IEC1 and IEC2), and two recombinant peptides (SA35 and SA40) from C. parvum sporozoites. The T-cell lines derived from the one recently infected donor had a higher proportion (26 to 38%) of T cells exhibiting the gamma/delta T-cell receptor (gamma/delta-TCR) than those from donors who had recovered from cryptosporidiosis several years earlier, suggesting that the gamma/delta T-cell population is involved in the early stage of the infection. The specific TCC had the alpha/beta-TCR, had the phenotype CD45RO(+) CD4(+) CD8(-), and were characterized by either hyperproduction of gamma interferon (IFN-gamma) alone, with a Th1 profile, or IFN-gamma hyperproduction together with interleukin-4 (IL-4) or IL-5 production, with a Th0 profile. SA35, SA40, IEC1, and IEC2 may be considered good targets of the cellular response against C. parvum and may play a role in maintaining the T-cell-mediated memory response to this parasite. Furthermore, the SA35 and SA40 peptides may be regarded as immunodominant antigens involved in the maintenance of the T-cell response in healthy C. parvum-sensitized persons.     

Metastatic pleural mesothelioma presenting with solitary involvement of the tongue: report of a new case and review of the literature

We report a new case of mesothelioma that presented with an isolated lingual metastasis 14 months after initial diagnosis. The patient was a 71-year-old man with a history of pleural decortication and chemotherapy for epithelioid mesothelioma who recently complained of chronic bleeding from a nodular consolidation of tongue. There was no clinical or instrumental evidence of extrathoracic tumor spread. Microscopic examination of a lingual biopsy specimen revealed nests of atypical polygonal cells with moderate cytoplasm, immunopositive for keratins, epithelial membrane antigen, vimentin, thrombomodulin, and calretinin. This case provides additional evidence that mesothelioma could rarely, but not exceptionally, metastatize, to unusual sites such as the tongue. In that location it can mimic primary poorly differentiated squamous carcinoma or adenocarcinoma as well as a number of other metastatic malignancies. In addition to obvious medicolegal implication, metastatic mesothelioma should be correctly recognized so as to avoid useless radical treatment.     

Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15-20% of cases.

The trisomy 8 found in malignancies may derive from a constitutional trisomy 8 mosaicism (CT8M), and in these cases the trisomy itself may be regarded as the first mutation in a multistep carcinogenetic process. To assess the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8, an informative sample of 14 patients was collected. The data ascertained included chromosome analyses of fibroblast cultures and of PHA-stimulated blood cultures in patients with normal blood differential count, as well as possible CT8M clinical signs. One patient showed trisomy 8 in all cell types analyzed and undoubtedly has a CT8M; a second patient consistently showed trisomy 8 in PHA-stimulated blood cultures when no immature myeloid cells were present in blood and should be considered as having CT8M; a third patient, with Philadelphia-positive chronic myelocytic leukemia, was more difficult to interpret, but the possibility that she had CT8M is likely. A few clinical signs of CT8M were also present in these three patients. Our data indicate that the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8 is approximately 15-20%.