Skin ulcerations as manifestation of vasculopathy in neurofibromatosis.

Vascular involvement in neurofibromatosis sometimes occurs and usually affects larger blood vessels of internal organs. We describe an unusual case of a now 41-year-old man with extensive skin involvement with ulcerations and histopathologic features of fibromuscular dysplasia, which has not been previously reported in the skin.

[Results of morphologic epidemiologic study of coronary arteries in Kaunas population aged 20-69 years: atherosclerotic lesions and their interrelationship]. / 20-69 metu Kauno gyventoju sirdies vainikiniu arteriju morfologinio epidemiologinio tyrimo duomenys: ateroskleroziniai pazeidimai ir ju sasaja.

OBJECTIVE: The object of study was the type, frequency and extent, as well as correlation of atherosclerotic lesions in Kaunas population aged 20-69 years. RESULTS: The frequency and intimal area of raised atherosclerotic lesions (fibrous and complicated plaque and calcinosis) are age-dependent. The increase of raised lesions area seems to alter at different decades of life. In men the most substantial progression in left anterior descending artery was observed at the fourth-fifth, in right coronary artery--at the fifth, and in both arteries of women - at the sixth decade of life. The area of fatty streaks is not dependent on age and comprises approximately 4-5% of intimal surface. We observed weak negative correlation between area of raised lesions and fatty streaks, and strong correlation between the area of all type of raised lesions in all three coronary arteries. CONCLUSIONS: The coronary artery atherosclerosis is progressing with age. Age decades, when increase of raised lesion area is observed, correspond to age periods, in which mortality due to ischemic heart disease increases significantly.

[Trends in the development of atherosclerosis in Kaunas population]. / Kauno gyventoju aterosklerozes raidos tendencijos.

The trends of development of atherosclerosis were evaluated by comparing the epidemiological morphological data from the seventh decade (first study, 1962-1965) and the tenth decade (second study, 1991-1993) of the 20th century. The first study included arteries from 818 patients (422 men and 396 women); whereas the second study included arteries from 1252 patients (958 men and 294 women). We have observed an age-independent increase in frequency and extent of the raised atherosclerotic lesions in aortas and coronary arteries of Kaunas men in the second study. Thus, the atherosclerosis has become more severe. The trends of development of atherosclerosis in aortas of Kaunas women were similar to those of men, but the atherosclerosis of coronary arteries did not progress until the fifth decade of life (the frequency of fibrous plaques in the left anterior descending artery was even lower, p < 0.05), and the area of raised lesions became larger only in the sixth-seventh decades. During the latter 20-30 years, the area of raised atherosclerotic lesions of abdominal aortas also increased in men in Riga, Tallinn, Tartu, Yalta, and elder men in Malmö as well as in Kaunas and Malmö women, aged 40-59.

CTLA4Ig combined with anti-LFA-1 prolongs cardiac allograft survival indefinitely.

CTLA4Ig and anti-LFA-1 are members of a new generation of immunomodulatory drugs which inhibit important signaling pathways in T cell activation. Both substances target molecules which have pivitol functions in the activation of CD4+ and CD8+ T cells and have been theorized to have an interdependent relationship. These drugs have been used independently in various treatment regimens and have shown great promise in prolonging the survival of allografts. In order to test whether these substances have synergistic or potentiating effects when combined, we performed mixed lymphocyte reactions, skin transplantation and vascularised heterotopic heart transplantation in the Balb/c (H-2(d)) to C3H/HeJ (H-2(k)) strain combination. When anti-LFA-1 and CTLA4Ig were combined at low doses, there was a substantial inhibition of lymphocyte proliferation. When each drug was used as a mono-therapy in skin graft recipients, there was no significant effect on median graft survival (anti-LFA-1, 15 days; CTLA4Ig, 16 days) when compared to untreated controls (13 days), whereas a combination of anti-LFA-1 and CTLA4Ig extended graft survival significantly to 32 days. Untreated vascularised heart grafts rejected at a median of 8 days, CTLA4Ig-treated mice rejected at a median time of 79 days and anti-LFA-1-treated mice rejected at 43 days (n = 9). When CTLA4Ig and anti-LFA-1 were combined, all animals had functioning heart grafts at 100 days after transplantation. Histological analysis of combined-therapy hearts showed no signs or only minor changes associated with chronic rejection. In conclusion, these results indicate a synergistic effect of combining anti-LFA-1 with CTLA4Ig in inhibiting lymphocyte proliferation and prolonging the survival of fully MHC-mismatched allografts.