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The authors investigated the possible correlation between blood concentrations and clinical outcome in 38 auranofin-treated patients with rheumatoid arthritis, diagnosed according to ARA criteria. The results showed that the whole blood gold concentrations did not correlate with the clinical parameters investigated and some laboratory findings. The authors discuss this lack of correlation, suggesting that a clear genetic disposition can interfere with the clinical response, affecting the metabolism and kinetics of the drug.

Combined pharmacologic and surgical criteria are evaluated for prevention of the metabolic changes which characterize the revascularization syndrome (r.s.). The procedures basically consist, prior to restore the arterial circulation, in a regional arterial wash-out using a solution which is pumped, either manually or by means of a peristaltic pump, in the vascular bed of the devscularized territory; the washing solution is then collected through a flebotomy conducted on the regional venous drainage and prevented from entering the blood stream.

From 1964 to 1977, 64 patients affected by aneurysm of the thoracic aorta were surgically treated at the 2nd Surgical Department of the University of Milan (Head: Prof. E. Malan). 25 patients had a true aneurysm and 34 a dissecting aneurysm. The various surgical techniques are discussed. The mortality rate and postoperative results are presented.

The effect of a supernatant (SN-A) obtained from PMA-stimulated IL-2 producing EL-4 cells on cytotoxic cell induction in thymocyte and splenocyte cultures was evaluated. SN-A, but not recombinant IL-2 alone, induced cytotoxic cell differentiation in thymus cell cultures, thus indicating that factors distinct from IL-2 are required for effector cell generation. INF-gamma takes part in the process, and Ia+ accessory cell presence is also strictly required in thymus cultures for lymphokine-induced cytotoxic cell generation. Cytotoxic activity in thymocyte cultures was due only to Thy 1+ Lyt 2+ cells having a broad spectrum of target cell specificity, while in spleen cell cultures an effector population with NK activity was also generated.

IL-2 was previously shown to induce cytotoxic effectors with a broad spectrum of target specificities in thymus and spleen cell cultures. This study was designed to show whether T cells activated by H-2 allogeneic cells in MLC or by syngeneic tumor cells in MLTC are also potential targets for these cytotoxic effectors. We found that thymocytes activated in vitro for 5 days by rIL-2 were capable of killing tumor cells as well as activated T cells. Thymocytes activated by IL-2 were accordingly utilized as a means of effecting clonal deletion of T cells activated by H-2 allogeneic target cells in MLC. To establish whether the unresponsiveness is specific. IL-2-activated thymocytes were added as third party cells to MLC and MLTC. The results showed that both T cells, proliferating in response to H-2 allogeneic cells, and CTL, reactive against syngeneic tumors or H-2 allogeneic cells, are eliminated from the T cell pool. Only alloreactive T cells are specifically eliminated in MLC by IL-2-activated thymocytes, as the remaining T cells are capable of proliferating and generating CTL in response to antigenically unrelated third party allogeneic cells. The possibility that unresponsiveness might be due to soluble factors was ruled out by studies performed with a diffusable "chamber insert" culture system. The results provide evidence that IL-2-activated thymocytes induce in vitro T cell tolerance.

CTL activation by specific targets leads to a rapid rise of inositol phosphates (InsPs) and of cytoplasmic-free Ca2+ concentration ([Ca2+]i). While these events are considered necessary to trigger granule secretion, Ca2+-independent cytolytic mechanisms have been recently proposed in addition or as an alternative to the classical Ca2+-dependent exocytosis model. We observed that lymphokine-activated killer (LAK) cells, obtained after stimulation with supraoptimal concentrations of IL-2 in short- or long-term cultures, kill susceptible targets in the absence of a [Ca2+]i rise and InsP3 formation. Moreover, LAK cell-mediated lysis was not associated with an increase in cytotoxic granule exocytosis, as evaluated by BLT-esterase release into the culture supernatant. Furthermore, using an antigen-specific CTL clone, which acquires LAK-like activity when cultured in medium containing high IL-2 doses, second messenger generation and cytolytic granule content secretion were not detected during lysis of unrelated target cells, while killing of specific targets triggered both these processes. These findings suggest that two lytic pathways may coexist in the same effector cells: a second messenger-dependent pathway involving degranulation, which is activated after TCR interaction with specific targets, and another pathway, independent of any known second messenger generation, responsible for unrelated target cell lysis.

The extreme variations with which atherosclerotic disease presents as regards progression index, arterial bed localization frequency, malignity and invasiveness in different ages and often as regards different anatomopathological aspects characterizing the formation and course of the primary lesion, mean that there are still many unknowns in the aetiopathogenesis, diagnosis and operative indications for this disease. Such problems are more and more important to the vascular surgeon who, with the development of atherosclerotic disease, sees the long-term results of his arterial reconstructive surgery compromised. The vascular surgeon is therefore directly involved with his colleagues in the internal medicine and pharmacological departments in problems connected with the pathogenesis of arteriosclerosis, and indeed he contributes to setting new constraints on the choice of prosthetic materials, for use in cases of bridge-work, and in the creation of new surfaces by means of thrombendarteriectomy. On the basis of such considerations, the IInd Surgical Clinic of Milan University began, in 1975, a study whose end purpose was the drafting of a clinical card designed for data computerization. Compiled by the surgeon, it is intended essentially for vascular surgeons. However, as it is personally considered that by the very nature of the disease, the atherosclerosis approach must be interdisciplinary, it also concerns physicians in the internal medicine, pharmacological and dietological departments.

In 20 patients suffering from osteoarthritis and treated with non steroidal anti-inflammatory drugs (NSAIDs) for one month sucralfate has been added for further two months. Endoscopic examination before/after this treatment confirmed the cytoprotective property of sucralfate, with normalization of the gastric mucosa and subsidence of subjective symptomatology.

Blood, plasma and serum viscosity, packed red cell volume, and plasma fibrinogen concentration was measured in a group of 13 subjects, suffering from peripheral obliterative arterial disease of the lower limbs (stage III or IV), awaiting surgery, and in 9 control subjects, none of whom showed signs of circulatory disease of the lower limbs either by clinical examination or by instrumental measurements. The blood samples were taken from the: (a) antecubital vein; (b) femoral vein; (c) femoral artery. In the patients venous blood viscosity was significantly higher than arterial blood viscosity. No significant differences have been found between the femoral and the antecubital vein, but in the femoral vein blood viscosity was slightly higher. Packed red cell volume and plasma viscosity were slightly but significantly higher in venous blood, while no difference was seen in serum viscosity and in plasma fibrinogen concentration. In the control subjects blood viscosity values were decidedly lower than in patients and no statistically significant differences were to be found between artery and vein, even if viscosity values were lower in artery. These results support the hypothesis that an interrelation exists between hyperivscosity syndrome and vascular ischaemia-inducing diseases.

Twenty patients suffering from acute lumbosacral syndromes (Group A) and eight patients suffering from acute gout (Group B) were treated with parenteral tiaprofenic acid (TA). In Group A TA was administered for 7 days at the dosage of 400 mg/daily for the first four days (1 200 mg vial i.m. in the morning, 1 in the evening), from the 5th to the 7th day with 200 mg/daily (1 vial in the evening) and, in Group B, TA was administered for 6 days at the dosage of 600 mg on the first day, (with 1 vial/8 hours of TA 200 mg by parenteral route) the 2nd and 3rd day with 1 vial/12 hours and the 4th and 6th day with 1 vial/daily in the evening. TA was found to be active on all clinical parameters evaluated. The tolerability was also good: only 4 patients with acute lumbosacral syndrome suffered from local pain.

BALB/c mice born to and nursed by females immunized against MSV-M showed a reduced tumour incidence and a high tumour regression rate following MSV-M injection at 7-14 days of age. Females immunized long before mating could also confer protection to their offspring whereas females immunized after parturition could not. A reduced number of tumours was observed in 3 out of 14 MSV-M injected litters whose mothers had been previously exposed to the virus while nursing infected offspring. Sera from suckling mice born to and nursed by immunized mothers contained MSV-M neutralizing antibody as shown by an in vitro focus reduction assay. Cell-free extracts from mice which developed leukaemia after MSV-M inoculation were tested for oncogenic activity in 1-week old mice. Out of 6 extracts, 4 induced typical MSV-M tumours and 2 caused leukaemias.