[Hepatic iron, iron depletion and response to therapy with peg-Interferon and Ribavirin in chronic hepatitis C. Pilot study]. / Ferro epatico, ferrodeplezione e risposta alla terapia con peg-Interferone e Ribavirina nell'epatite cronica C. Studio pilota.

AIM: To estimate whether pretreatment serum iron levels, the HIC (hepatic iron concentration) and the distribution of hepatic iron identify the long-term "responders" and "non-responders" to therapy with peg-IFN and RBV, and whether the addition of phlebotomy could increase the likelihood of therapeutic response. PATIENTS AND METHODS: 45 subjects with chronic hepatitis C were taking peg-IFN alpha-2a 180 microg once a week and RBV 1000 mg/die. The "responders" continued therapy with peg-IFN plus RBV, while, the "non-responders" were subjected to phlebotomy. After two weeks and subsequently every month the patients were subjected to blood test and clinical appraisal. RESULTS: Hepatic iron storage meaningfully conditions the outcome of therapy with peg-IFN and RBV, its reduction by phlebotomy favourably correlates with response to treatment and, at last, the semiquantitative histological appraisal would have to be included in the pre-treatment work-up of patients with chronic hepatitis C. CONCLUSIONS: The study results, even though obtained on a small size of cases, allow to conclude that serum corporeal iron evaluation underestimates the real hepatic iron concentration; the hepatic iron concentration, in turn, negatively conditions the response to therapy with peg-IFN and RBV (by reducing the percentage of the fast virological response). Lastly, iron removal by phlebotomy favourably correlates with the response to treatment.

Chemohyperthermia for advanced abdominal malignancies: a new procedure with closed abdomen and previously performed anastomosis.

ChemoHyperthermic Peritoneal Perfusion (CHPP) after cytoreductive surgery is a relatively new procedure in the treatment of abdominal carcinomatosis or sarcomatosis. An assessment of the CHPP technique performed on 20 patients suffering from abdominal malignancies was carried out. After surgical debulking and gastrointestinal anastomosis, two Tenckhoff catheters were positioned for the immediate performance of CHPP, which was carried out at 42-43 degrees C for 1 h, after closing the abdomen. In 19 assessable patients, 47.3% and 36.8% complete responses (CR) were recorded at 1 and 6 months, respectively, with responses of 37.5% in patients affected with gastrointestinal cancer and 50% in patients affected with ovarian cancer. CR were obtained only in patients who had undergone accurate peritoneal debulking. Survival rate for gastrointestinal and ovarian cancer was 68% at 12 months. Patients who underwent radical cytoreductive surgery are all alive at a follow-up median time of 17 months. Two anastomotic leakages with spontaneous recovery were observed, along with one hydrothorax, which was immediately drained during the procedure, three cases of chemotherapic gastrointestinal toxicity, one sepsis, one renal failure that required a transient dialysis, and one cholecystitis that required cholecystectomy. One patient died 30 days after CHPP of a cardiac ischaemia not strictly related to the surgical procedure. In the authors' experience, CHPP with closed abdomen after reconstructive gastrointestinal surgery is a safe and feasible treatment with acceptable side effects.

Quantitative assessment of salivary gland inflammatory infiltration in primary Sjögren's syndrome: its relationship to different demographic, clinical and serological features of the disorder.

The aim of this study was to investigate the possible relationship between the degree of inflammatory infiltration of salivary glands in Sjögren's syndrome (SS) and the different demographic, clinical and serological features of the disease. A quantitative assessment of the extension of the infiltrates was performed on histology samples from the labial salivary glands (LSG) of 82 patients with primary SS, by calculating the ratio of the infiltrated area to the total area of glandular tissue in the samples. The correlations between the amount of inflammatory infiltrate and the main features of the disorder were then analysed. A significant negative correlation between the degree of LSG infiltration and the patient's age at disease onset was observed (P < 0.05). In contrast, the percentage of infiltrate did not correlate with the disease duration. A significant correlation was found between the degree of infiltration of the salivary tissue and (i) the total number of extraglandular features (P < 0.01) and (ii) the presence of specific extraglandular features such as Raynaud's phenomenon (P < 0.05), vasculitis (P < 0.0001), lymph node or spleen enlargement (P < 0.05) and leucopenia (P < 0.02). Finally, patients with antinuclear antibodies, anti-SSA/Ro antibodies, or anti-SSA/Ro plus anti-SSB/La antibodies showed a more widespread inflammatory infiltration in the LSG tissue than patients without these autoantibodies (P < 0.01). The degree of infiltration in the salivary tissue was significantly greater in those patients with anti-SSA/Ro plus anti-SSB/La antibodies in their sera than in patients with anti-SSA/Ro antibodies alone (P < 0.05). In conclusion, patients with SS and active inflammatory infiltration of the salivary glands usually experience an earlier disease onset and a larger number of systemic extraglandular manifestations. In addition, the antibodies directed against certain nuclear/cytoplasmic specificities, and particularly those which react with the SSB/La antigen, seem to play a key role in enhancing the autoimmune process in the salivary glands.

Multiple and reversible osteolytic lesions: an unusual manifestation of behcet's disease.

We describe a patient with Behcet's disease (BD) who developed multiple and reversible osteolytic lesions during the course of disease. The possible relationships between BD and this very unusual manifestation are discussed.

Assessment of the European classification criteria for Sjögren's syndrome in a series of clinically defined cases: results of a prospective multicentre study. The European Study Group on Diagnostic Criteria for Sjögren's Syndrome.

OBJECTIVE: To assess the recently proposed preliminary criteria for the classification of Sjögren's syndrome (SS) in a multicentre European study of a new series of clinically defined cases. METHODS: The criteria included six items: I = ocular symptoms; II = oral symptoms; III = evidence of keratoconjunctivitis sicca; IV = focal sialoadenitis by minor salivary gland biopsy; V = instrumental evidence of salivary gland involvement; VI = presence of autoantibodies. Each centre was asked to provide five patients with primary SS, five with secondary SS, five with connective tissue diseases (CTD) but without SS, and five controls (patients with ocular or oral features that may simulate SS). The preliminary six item classification criteria set was applied to both the SS patients and the non-SS controls, and the performance of the criteria in terms of sensitivity and specificity was tested. RESULTS: The criteria set was tested on a total of 278 cases (157 SS patients and 121 non-SS controls) collected from 16 centres in 10 countries. At least four of the six items in the criteria set (limiting item VI to the presence of Ro(SS-A) or La(SS-B) antibodies) were present in 79 of 81 patients initially classified as having primary SS (sensitivity 97.5%), but in only seven of 121 non-SS controls (specificity 94.2%). When the presence of item I or II plus any two of items III-V of the criteria set was considered as indicative of secondary SS, 97.3% (71 of 73) of the patients initially defined as having this disorder and 91.8% (45 of 49) of the control patients with CTD without SS were correctly classified. CONCLUSION: This prospective study confirmed the high validity and reliability of the classification criteria for SS recently proposed by the European Community Study Group.

Immunotherapy in rheumatoid arthritis: a review.

The starting mode of the pathological process in rheumatoid arthritis (RA) is the presentation of an unknown 'rheumatoid' antigen by an antigen presenting cell to the receptor on the CD4+ T cell. The activation of the CD4+ T cell, and consequently of the cytokine network, is the second step in the inflammatory process. Immunosuppression in RA, obtained using either immunosuppressive drugs (azathioprine, cyclophosphamide, methotrexate), or physical procedures (lymphoapheresis, total lymphoid irradiation) acts specifically on all lymphocyte populations, and can induce a number of side effects, such as myelotoxicity and opportunistic infections. Two promising new therapeutic approaches are being developed, one aimed at specifically reducing the proliferation of activated T cell clones, and the second designed to modulate the activity of the cytokines involved in the inflammatory process. Encouraging results have been so far obtained with: a) cyclosporine A, a somewhat more specific immunosuppressive agent; b) monoclonal antibodies against surface antigens (CD4, CD5, CD7, CD25, CD54) expressed on activated T cells; c) T cell vaccination; and finally (i.v.) recombinant cytokines, their agonists or antagonists. Besides their utility in the treatment of the disease, these new therapeutical procedures should also lead to a better understanding of pathological processes in RA.

Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. III. Development of a computerised clinical chart and its application to the comparison of different indices of disease activity. The European Consensus Study Group for Disease Activity in SLE.

In the first phase of this study, a data-base containing clinical and laboratory findings of 704 patients with systemic lupus erythematosus (SLE), originating from 29 centres and 14 countries, was used to assess the validity of 4 common indices of disease activity, SLAM, BILAG, SLEDAI and SIS. The physician's judgement of activity was assumed as the unique reference criterion (gold standard). Computer programmes were developed to calculate automatically the 4 activity indices; this computation appeared to correspond with manual computations in a sample of 60 appropriately selected cases. All 4 indices were closely correlated with each other (r in the range of 0.716 to 0.872), and with the physician's score (r in the range of 0.620 to 0.719). In the second phase of the study the activity index developed in part I (ECLAM) was prospectively validated, and its performance compared to that of the other scales, both as a single state index and as a transition index (i.e., its ability to assess disease activity at a single point in time and to detect variations in consecutive readings). A computer-assisted clinical chart was prepared for this purpose. This chart allowed us to calculate automatically all the indices. Two consecutive observation times (time 0, and time 1 three months later) were included in the study protocol. Data on 75 patients from 19 centres were collected, and each patient was observed twice. All the computed indices were closely correlated, both at time 0 (r ranging from 0.725 to 0.884), and at time 1 (r ranging from 0.607 to 0.833).(ABSTRACT TRUNCATED AT 250 WORDS)

Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. II. Identification of the variables indicative of disease activity and their use in the development of an activity score. The European Consensus Study Group for Disease Activity in SLE.

A European Consensus Group study, involving 29 centres from 14 countries, was performed in order to reach agreement on the definition of disease activity in systemic lupus erythematosus (SLE) and to construct a new disease index. Data on 704 lupus patients were collected and analysed, using univariate and multivariate statistical procedures, to select those clinical and laboratory features of the disorder which best correlate with the global assessment of disease activity assigned to the patients by the physician of each participating centre. A combination of 15 clinical and laboratory variables was shown to be the best predictor of disease activity in SLE. A European Consensus Lupus Activity Measurement (ECLAM) was then formulated. This index included the 15 selected variables, weighted (with some adjustments) according to their respective regression coefficients in the multivariate model. ECLAM appears to be an effective instrument for scoring patients with different degrees of disease activity. This is the first SLE disease activity index based on data from a very large number of lupus patients followed at a large number of lupus centres in different countries. It might therefore very well serve as a standardised measure for future European clinical studies. Final assessment of the validity, reliability and sensitivity of this index is now underway.

Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. I. A descriptive analysis of 704 European lupus patients. European Consensus Study Group for Disease Activity in SLE.

Using a detailed questionnaire, the cumulative historical and current demographic, clinical and serological data on 704 SLE patients from 29 European centres and 14 countries have been assessed. Ninety-three percent of the patients were Caucasian and the female/male ratio was 10:1. Analysis of the cumulative incidence showed that arthralgia/arthritis (94%), rash (69%), Raynaud's phenomenon (49%), serositis (44%) and renal disease (38%) were the most frequent clinical manifestations. Virtually all the patients (98%) were antinuclear antibody positive, while anti-ds-DNA antibodies (76%), hypocomplementaemia (71%) and anti-Ro(SSA) antibodies (35%) were frequent serological abnormalities. Whilst much of this data is in line with previous reports, it is notable that renal, lung, and central nervous system involvement and the frequency of rheumatoid factor, anti-Sm and anti-RNP antibodies were much lower than in most comparable series in the United States. We assume that ethnic differences and the greater present awareness of lupus could explain this variations. Low dose corticosteroids, non-steroidal anti-inflammatory drugs and anti-malarials were used to treat over half of the patients, 75% of whom were between 15 and 55 years of age. This report offers a useful overview of lupus both clinically and serologically in Europe in the 1990's.

[Partial replacement of the ureter with lyophilized human dura mater. Experimental research (author's transl)]. / Sostituzione parziale di uretere con dura madre umana liofilizzata. Ricerche sperimentali.

In order to evaluate whether and how for lyophilized human dura mater deserves to be used in the field of ureteral alloplastic surgery, the authors present and discuss the results they obtained during the course of experimental research. In the light of their personal histological documents, they stress the absence of reject phenomena, a property which, together with the absence of precipitates, the complete reepithelialisation of the transition epithelium and the ability to ensure normal ureteral perviousness, evidences that lyophilised human dura mater has full rights to a place in substitutive surgery of a segment of ureter, in particular the lumbo-liiac segment.