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In SSc, PNS ultrastructure damage is linked to the progression and severity of skin involvement. The alterations evolve from the early to the advanced phase mainly in the diffuse subset. In particular, the severe PNS lesions found in advanced lSSc are already present and widely diffuse in early dSSc and the microvascular involvement in early lSSc seems to precede the modification of the PNS in the skin. Thus, an early therapeutic approach can be useful to reduce the progression of PNS and skin damage in SSc patients.

Aims-To investigate changes in morphology ofthe developmental stages ofEnterocytozoon bieneusi and symptomatic relief observed in AIDS patients after treatment with furazolidone. Methods-Six AIDS patients with symptomatic E bieneusi infection of the small intestine were treated with a course of furazolidone. All patients had a weekly monitoring of parasite shedding in stool by light microscopy during and after treatment. At the end of the treatment, duodenal biopsy specimens obtained from three patients were studied by transmission electron microscopy by two pathologists who were unaware of the patients' treatment.Results-Al patients showed both clinical and parasitological response with transient clearance or decrease of spore shedding in stool. After treatment, alterations in faecal spores were observed in all patients by light microscopy, and ultrastructural changes in E bieneusi at all stages of the life cycle were demonstrated in biopsy specimens of the three patients who underwent post-treatment endoscopy.Conclusions-The clinical benefit seen after treatment with furazolidone in six AIDS patients with E bieneusi intestinal infection may be due to damage to the developmental stages causing a partial inhibition to reproduction of the parasite.

Aims-To investigate the eVectiveness of long term, low dose azithromycin treatment for chronic cryptosporidiosis in patients with AIDS. Methods-Azithromycin was administered as initial daily treatment to 13 patients with AIDS: 6 patients received 500 mg for 30 to 40 days (mean 35); 3 patients received 1000 mg for 21 to 50 days (mean 37); and 4 patients received 1500 mg for 20 days. Nine of the 13 patients were also given low dose maintenance treatment with diVerent schedules of azithromycin for 30 to 360 days (mean 129). Patients were monitored, during and after treatment, for parasite shedding in stool and for daily stool frequency and body weight. All but one patient had severe immunodeficiency. Results-Long term, low dose maintenance treatment was associated with major clinical and parasitological benefits: there was probable eradication of infection in 2 patients, and 7 patients showed a complete response with persistent high decrease (5 patients) or clearance (2 patients) of parasite in stool. The drug was well tolerated, and there was no relapse either during treatment or during follow up (up to 21 months). These results were more impressive than those observed after the short term initial course of azithromycin, which was unable at any tested dose to achieve parasite clearance in stool (except in the patient with less advanced immunodeficiency) or to prevent relapse in 3 patients who discontinued treatment. Reversible side eVects occurred with the 1500 mg daily dose. Conclusions-Long term, low dose azithromycin is well tolerated and may induce stable remission of chronic cryptosporidiosis in patients with AIDS. It may lead to probable eradication of the infection in some patients, even those with severe immunodeficiency. (J Clin Pathol 1998;51:138-142)

showing the features characteristic of the ileocaecal junction. In particular, the inner portion of the circular muscle showed a peculiar arrangement and was thicker than elsewhere. These results show that in humans the caecocolonic junction is provided with a sphincter morphology and function. Little is known about its physiological relevance in ileal flow accommodation and caecal filling and emptying but it should not be underestimated with regard to some colonic motility disorders. (Gut 1995; 37: 493-498)

BackgroundAngiogenic T cells (Tang) have been recently identified within colonies of endothelial progenitor cells (EPCs) as mediators of endothelial repair. Both Tang and EPCs are reduced in rheumatoid arthritis and this contributes to persistent endothelial damage and eventually increased cardiovascular risk. In primary Sjögren’s syndrome (pSS), EPCs are expanded but no data are currently available about Tang.ObjectivesAim of this study was to assess Tang (CD3 +CD31+CXCR4+) in peripheral blood (PB) and target organs of pSS as well as the association with EPCs (CD34 +CD133+VEGFR-2+) and clinical and serological features of the disease.MethodsThirty-six pSS patients and 20 sex- and age-matched healthy donors (HD) were enrolled. Phenotipic analysis of peripheral blood mononuclear cells was performed by flow cytometry using FITC, Pe, Pe-Cy7 or AlexaFluor647 labelled anti-human CD3, CD31, CXCR4, CD4, CD8, CD28, CD34, CD133, VEGFR-2, and IL-17 antibodies. Minor salivary gland (MSG) biopsies from 8 pSS patients were studied and compared to samples from 12 patients with sicca symptoms and either non-specific chronic sialadenitis (NSCS) or normal parenchyma (n=6 each). MSG sections were subjected to immunofluorescence staining to assess the presence of CD3 +CD31+CXCR4+Tang cells and the expression of the CXCR4-ligand CXCL12/SDF-1 chemokine.ResultsCirculating Tang were expanded in pSS compared to HD and were directly correlated to EPCs. Both Tang and EPCs directly correlated with disease activity as calculated with the EULAR Sjögren’s syndrome disease activity index (ESSDAI). Over 60% of Tang lacked CD28 revealing a senescent phenotype. Only a small proportion of Tang displayed either CD4 or CD8, the majority of Tang being therefore CD4-CD8- double negative (DN). A subset of Tang produced IL-17 and the highest proportion of IL-17-producing cells was observed among DN cells. Immunofluorescence analyses revealed the exclusive presence of infiltrating Tang cells along with increased expression of CXCL12/SDF-1 in pSS MSGs compared to either NSCS or normal MSGs.ConclusionsCirculating Tang cells are expanded in pSS, display a senescent phenotype, are mainly CD4-CD8- DN and produce IL-17. Moreover, Tang cells home to and infiltrate MSGs in pSS, presumably through the SDF-1/CXCR4 chemotactic axis. Our data suggest that besides their positive effect together with EPCs in endothelial repair, Tang cells may contribute to disease pathogenesis.Disclosure of InterestNone declared

This work was undertaken to assess the role of endothelial E-selectin in the development of neutrophil accumulation into the ischemic and reperfused human skeletal muscle and eventually in the genesis of ischemia-reperfusion syndrome. Twelve patients affected by abdominal aortic aneurysm who were undergoing reconstructive vascular surgery were studied. Muscle biopsies from the right femoral quadriceps were taken (1) immediately after anesthesia, as control samples, (2) before declamping the aorta, as ischemic samples, and (3) 30 minutes after reperfusion and then processed for immunohistochemical and ultrastructural analysis. Immunohistochemistry revealed a strong positive reaction for E-selectin on the venular endothelium during ischemia and reperfusion. Ultrastructural investigation showed that reactivity for E-selectin matched neutrophil accumulation of the skeletal muscle tissue. This phenomenon was dependent upon a complex series of events that included neutrophil adhesion to the inner surface of the postcapillary venules, passage through endothelial intercellular junctions, and migration distally into the interstitial spaces of the skeletal muscle tissue. Neutrophil tissue infiltration was also associated with ultrastructural signs of tissue damage at reperfusion. This is in agreement with accumulating evidence indicating a role for tissue infiltrating neutrophils in the genesis of toxic O2 free radicals. Our data suggest that E-selectin expression on the vascular endothelium of human skeletal muscle may represent a key regulatory point in the process of neutrophil tissue accumulation and indicate an active role for the venular endothelium in the development of human ischemia-reperfusion syndrome.