Study of lymphocyte costimulatory molecules in renal transplantation.
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Biomedical subjects
Publications and source records attributed to L Gastaldi.
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BACKGROUND AND AIMS OF THE STUDY: The aim of this study was to evaluate the long-term follow up of the Pericarbon pericardial bioprosthesis implanted in the mitral position. METHODS: Between January 1985 and January 1991, 78 patients (26 males, 52 females; mean age 56.9 +/- 7.8 years) underwent isolated mitral valve replacement with a Pericarbon valve. All bioprostheses were size 29 mm and implanted by the same surgeon. RESULTS: Total follow up was 663.2 pt-years and it was 97% complete. Early mortality was 1.3% (1/78); two minor cerebral embolisms were observed as early complications. At 12 years the overall survival rate was 85.0 +/- and valve-related survival 93.1 +/- 3.0%; freedom from embolic events was 83.0 +/- 4.5% and from endocarditis 98.7 +/- 1.3%. Freedom from primary tissue failure was 56.8 +/- 6.6%; it was 86.3 +/- 7.5% in patients aged > 60 years and 36.8 +/- 8.2% in younger patients. There were 27 reoperations, 26 for primary tissue failure, one for endocarditis. Comparison between basal and follow up echocardiographic studies showed a significant stenotic deterioration of the bioprosthesis and a negligible incidence of regurgitation. Morphological findings of explanted bioprostheses were characterized by stenotic and diffuse microcalcification, but no tissue tear was observed. CONCLUSIONS: These results confirm that the Pericarbon bioprosthesis is structurally safe and free from the fatigue problems which afflicted the first and second generation of pericardial valves. As with other tissue valves, the rate of calcification is age-dependent, suggesting preferential use of the Pericarbon prosthesis in elderly people.
BACKGROUND: Biological activity of interleukin-1 (IL-1) depends on the number and type of IL-1 receptors on target cells and on the amounts of its naturally occurring inhibitor, the IL-1 receptor antagonist (IL-1ra). METHODS: Expression of IL-1 receptor was studied on the peripheral blood mononuclear cells of 20 end-stage renal-disease patients maintained by chronic haemodialysis by means of either polysulphone (10 patients) or cuprophane membranes (10 patients) and compared to that of normal controls. Plasma and cellular levels of IL-1ra and IL-1 beta were also measured. RESULTS: The proportion of monocytes expressing the IL-1 receptor was strikingly higher in haemodialysis patients than in the healthy population. This proportion further increased during haemodialysis with cuprophane but not with polysulphone. Expression of the IL-1 receptor on lymphocytes was very low in both controls and dialysed patients; in the latter there was no intradialytic variation. Plasma concentrations of IL-1 beta and IL-1ra were elevated in haemodialysis patients and undetectable in controls. Whereas plasma IL-1 beta decreased throughout haemodialysis, IL-1ra further increased, with no significant differences between the two membranes used. Total cellular IL-1 beta and IL-1ra were also higher in the patient group than in the healthy controls. A further increase of both IL-1 beta and IL-1ra was detected at the end of the haemodialysis session with any membrane. CONCLUSIONS: Monocytes of haemodialysis patients circulate in a state of activation, which makes them both producer and target of IL-1. Thus there is an autocrine upregulation of IL-1 production. Although IL-1ra levels are high, they are most likely to be expression of monocyte activation rather than represent effective inhibitors of IL-1 activity.
Stapling instruments are being currently used for digestive or colorectal anastomoses with definite advantages. The authors report their initial clinical experience about BAR utilization to restore intestinal continuity after upper digestive and colorectal resections. The authors have been carried out 20 anastomoses on 18 patients: 11 males and 7 females. Eleven (61.1%) of them were affected with malignant neoplasms and in 9 cases were performed an urgency procedure. The colorectal and jejunal-jejunal anastomoses were performed, respectively, in 8 cases; gastric-jejunal and ileo-colic anastomoses, respectively, in 2. The satisfactory results obtained seem to demonstrate that the biofragmentable anastomotic ring constitutes a "safe" method of bowel junction of the whole digestive apparatus.
Conservative surgery followed by radiotherapy is the current treatment of choice for primary breast cancer: indeed, this protocol ensures local control, relatively good cosmetic results and NED survival values similar to those of more invasive surgery. Radiotherapy requires the optimization of the irradiation technique to minimize the dose to the organs at risk. To this purpose, 30 patients submitted to quadrantectomy for breast carcinoma and then to radiotherapy on the residual breast were examined, January through December, 1994, at the Radiotherapy Service of the Ivrea Hospital, to investigate if CT can help optimize treatment planning, sparing as much of the pulmonary tissue underlying the residual breast as possible. Our series of patients was then compared with a literature series whose treatment had been planned only on the mapping of body outline. Some interesting considerations follow from our results: 1) With CT, larger fields can be used than those used with the body outline, so that the planned target volume can be more closely approached; 2) Larger fields can be used because the critical organ included in the irradiation field is more correctly and precisely defined; 3) The comparison with the literature shows that in the past the fields were larger, because the target volume and the critical organ were more difficult to define. The use of larger fields means a higher dose to the lung and thus maybe a higher risk of radiation pneumonia.
Pericardial heart valve bioprostheses have been utilized for 20 years. In spite of encouraging initial results, long-term follow-up showed a higher incidence of structural failures and primary tissue failures than porcine bioprostheses. Pericarbon represents the newest generation of bovine pericardial bioprostheses. Aim of this study is the long-term evaluation with echocardiographic and color Doppler technique of an innovative bioprostheses, in particular, its morfological and functional characteristics. From 1985 to 1989, 78 consecutive patients (21 males, 57 females, mean age 56.5 +/- 8.16 years) underwent mitral valve replacement with Pericarbon 29, by the same operator, who preserved the mitral posterior leaflet. One month after operation, 21 of these patients underwent echo-color Doppler evaluation, in normalized hemodynamic conditions (normality ranges). In 1995, at the end of the followup, 30 of the remaining 54 patients underwent new echo-color Doppler evaluation and these data were compared with normality ranges values. Leaflets' thickness increased from 0.98 +/- 0.09 to 2.87 +/- 0.73 mm (anterior leaflet; p < 0.0001) and from 1.02 +/- 0.08 to 2.71 +/- 0.45 mm (posterior leaflet; p < 0.0001) 43.3% of anterior leaflet and 53.3% of posterior leaflet showed fibrocalcic lesions. Mean transvalvular gradient increased from 3.4 +/- 0.2 to 6.6 +/- 3.4 mmHg (p < 0.0001); also functional area decreased (p < 0.0001). We have found no paraprosthetic regurgitation and a very low number of central prosthetic regurgitation. Left ventricular function, evaluated by ejection fraction and regional kinesis, remained substantially preserved.
The results of 93 elderly patients, subdivided in two age groups (> 65 < 80 years; > 80 years), undergoing abdominal surgery in immediate or delayed emergency over the past five years are reported. The overall morbility was 47.3% (48 complications in 44 patients); among the complications, sepsis was the first factor in frequency in either group (group I: 28.1%, group II: 17.2%), and was reported mostly in patients with associated diseases (group I: 61.1%, group II: 60%). Overall mortality was 16.2% (group I: 15.6%, group II: 17.2) related to 15 patients; among them, 10 had associated diseases (66.6%). The authors try to identify risk factors and their influence in prognosis and propose a multidisciplinary approach in the pre and postoperative period.
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Ureterocele is a congenital urinary abnormality characterized by the presence of an intra-bladder hernia or cystic ballooning of the lower end of a ureter between the mucosa and muscle of the bladder. The abnormality leads to urinary retention and recurrent urinary tract infection which can cause irreversible damage to the kidney. Antenatal ultrasound diagnosis of ureterocele is possible but remains difficult. The disease is confirmed during radiologic examination after birth, and renal function is assessed by 99mTc-DMSA. Ureterocele, while not an uncommon pediatric urologic problem, has been reported only rarely in adults. It is bilateral in 10% of cases, is rare in black people, and requires thoughtful management decisions. A relatively uncommon case of bilateral ureterocele with single ureter, associated with left vesicoureteral reflux, in African black man is reported. The patient was investigated by ultrasonography and intravenous urography. Surgical transvesical right "osteoplasty" and excision of the left ureterocele plus ureteric reimplantation, using Politano-Leadbetter technique, were performed. The surgical approach to ureterocele is discussed and we underlined the difficulty of therapeutic decisions, especially if surgery is considered.
To evaluate the presence of diabetic cardiomyopathy, we measured various parameters of left ventricular systolic and diastolic function by means of M-mode and Doppler echocardiography in 50 IDDM children (mean age 13 +/- 3 years; mean IDDM duration 5.9 +/- 4.1 years) free of cardiovascular symptoms. As compared to age-matched healthy control subjects, diabetic children evidenced a significant increase in mean values of pressure half time (PHT), an index of the early diastolic phase (53.7 +/- 10.2 msec vs 44.5 +/- 9, p < 0.002). When the patients were subdivided on the basis of IDDM duration, metabolic control and the presence of retinal microangiopathic abnormalities, those with longer IDDM duration and poor glycemic balance had higher PHT values. These data indicate that an early diastolic dysfunction, expressed by reduced left ventricular compliance, can be found in children with Type 1 diabetes mellitus of relatively short duration. Doppler echocardiography is a reliable non-invasive means to assess early impairment of cardiac function in IDDM patients.
Chordal preservation during mitral valve replacement is thought to greatly preserve left ventricular function. Recently a stentless mitral valve (Biocor) became available for clinical use. It is a porcine mitral valve with the entire chordal apparatus, the sewing ring being reinforced by a bovine pericardial ring and the chordae being sutured together onto two pericardial patches. During a six months period, seven patients undergoing mitral valve replacement for mitral insufficiency (four cases), mitral stenosis (two cases) or mixed lesions (one case) received a stentless mitral valve. Their mean age was 66.3 +/- 4.8. The valve was implanted by suturing the pericardial patches onto the papillary muscles and the sewing ring onto the mitral annulus. Echocardiography control immediately after surgery showed good valve function. Three valves failed after a period of seven days, seven and 12 months respectively. The valve lesions were similar and consistent with an excessive tension on the chordae and on the valvular tissue. There were tears along the posterior annulus and at the level of the commissures, often accompanied by chordal rupture. Histology and scanning electron microscopy showed good integration of the prosthesis with the patients own tissues. There were areas of overgrowing tissue without endothelial cells especially in the area of papillary muscle -pericardial patch interaction. The remaining four patients continue to do well after a mean follow up of two years. The apparent excessive tension on the valve tissues leading to the premature failure of the prosthesis could be due to the variability in the distance between mitral annulus and papillary muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was planned to investigate the effect of ischemic dysfunction of the free wall of the right ventricle on right and left ventricular performance in the presence of a normally contracting interventricular septum. The experiments were performed in 6 anesthetized dogs in which echocardiogram, electrocardiogram, aortic blood pressure and left and right ventricular pressure were recorded. In the dog, the contractility of the septum is not affected by the occlusion of the right coronary artery which does not perfuse this part of the myocardium. Complete occlusion of the major individual ventricular branches and partial occlusion of the main right coronary artery did not impair right ventricular performance. Only complete occlusion of the main artery affected right and left ventricular function as revealed by echocardiogram. Reduced output by the ischemic right ventricle caused a reduction in left ventricular diastolic and systolic dimensions and in left ventricular developed pressure without any effect on left ventricular end-diastolic pressure.
Cyclosporine (CsA) dosing is based on CsA plasma or blood concentrations measured 12 to 24 hours after drug administration (trough levels). This study evaluated the relationship between the timing of CsA concentrations and subsequent pharmacokinetic parameters to predict an optimal sampling period. Plasma samples were obtained from 22 patients before their morning dose of CsA and at 2, 4, 6, 8, 10, and 12 hours after the dose on the 7th and on the 21st day after heart transplantation. The plasma samples were assayed by both HPLC and FPIA. The Cmax for CsA was achieved over a period ranging from 2 to 6 hours (mean/median = 4.7/4.0) during the day 7 and the day 21 studies. The mean (+/- SD) half-life was 3.2 (1.0) hours on day 7 and 2.9 (1.1) hours on day 21, (P > 0.05); the mean apparent oral clearance was 276 (117) L/hr on the day 7 and 269 (209) L/hr on day 21, (P > 0.05). When CsA plasma concentration by either FPIA and HPLC was monitored, the drug concentration best correlated with AUC was found to correspond to the plasma samples taken 4 to 8 hours after drug administration. The authors conclude that through blood sampling for therapeutic drug monitoring of CsA is not optimal, and that further studies are necessary to correlate concentration monitoring during the dosing interval with pharmacologic and toxicologic parameters.
The role of hemodialysis (HD) as an arrhythmogenic event has recently been emphasized. We studied 18 patients by Holter monitoring, comparing the arrhythmogenic effect of acetate dialysis (AHD) and bicarbonate dialysis (BHD). The frequency of ventricular arrhythmias was 93 +/- 66/h in AHD and 32 +/- 26/h in BHD (p less than 0.005). According to the classification of Lown and Graboys, classes III and IV were more often to be found in AHD than in BHD and no patient on BHD was in class IVB and class V. Five patients affected with ischemic heart disease had more frequent and dangerous ventricular arrhythmias than the others; a significant difference between buffers was recorded in all cases but 1. Intradialytic changes in body weight, hematocrit, osmolarity, ionized calcium and potassium during AHD and BHD were similar. The two methods only differed in the quickness and degree of correction of acidosis, and this was related to a significant difference in intraerythrocytic potassium at the end of the session. The quicker and more regular correction of acidosis with BHD and the consequent difference in ionic flows between the intra- and extracellular spaces, as demonstrated by changes in intraerythrocytic potassium at the end of the session, could account for the seemingly less arrhythmogenic effect of BHD.
We have studied the role of interleukin-2 (IL-2) and its receptors in the impaired in vitro lymphocyte response characteristic of hemodialysis patients treated by means of cuprophane membranes. The proliferative response of T lymphocytes as well as T-cell-dependent B cell proliferation after stimulation with mitogens was significantly reduced in hemodialysis patients. The in vitro production of IL-2 after such stimulation in parallel cultures was found to be similar in patients and in controls. The expression of IL-2 receptor on the lymphocyte cellular membrane in the hemodialysis group was also similar to controls. The in vitro proliferative response of uremic lymphocytes to exogenous IL-2, however, was significantly depressed suggesting a reduced availability of biologically active IL-2 receptor. The release of soluble IL-2 receptor by lectin-stimulated lymphocytes in culture was also significantly lower in the patient group; yet, hemodialysis patients has a strikingly elevated level of plasma soluble IL-2 receptor, and similar high levels were also found in three other groups of end-stage renal disease patients dialyzed by means of cellulose acetate, polysulfone and polyacrylonitrile membranes, as well as in a group of uremic patients on conservative treatment. In the hemodialysis patient group a significant positive correlation between levels of soluble IL-2 receptor and the duration of hemodialysis was found. Since soluble IL-2 receptor has been reported to down-regulate lymphocyte responses, the elevation in plasma levels of soluble IL-2 receptor in hemodialysis patients may be a pathogenetic factor in the progressive development of impaired immunity associated with end-stage renal disease.
Previous studies have shown that transient increases in aortic blood pressure obtained by occlusion of the descending thoracic aorta, in anesthetized dogs with beta-blockade and vagal section, did not affect coronary vascular resistance apart from a non-significant increase just after release of the constriction. The present study examined whether this response also occurred in the normally innervated heart. Experiments were carried out in six anesthetized dogs, in which pressure in the aortic root and in the left ventricle, as well as flow in the left circumflex coronary artery, were recorded. Coronary vascular resistance was calculated as the ratio of the difference between aortic pressure and left ventricular pressure to coronary circumflex flow during the slow inflow phase. Before occlusion coronary vascular resistance was significantly lower than during the same period in the previous studies using animals with beta-blockade and vagal section. During the occlusion, in contrast with the previous investigation, the increase in aortic pressure caused a significant increase in coronary vascular resistance 10 seconds after the beginning of the occlusion. Coronary vascular resistance was further increased immediately after release of the occlusion, concomitantly with the decrease in aortic pressure, which fell abruptly below the control level. The increase immediately after the release of the constriction was qualitatively similar, but greater in extent, to that observed in the animals with vagal section and beta-blockade. These differences are assumed to depend on a lower vasomotor tone in the normally innervated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
The Abbott TDx fluorescence polarization immunoassay (FPIA) procedure for measuring cyclosporine A (CsA) was evaluated and compared with the Sandoz polyclonal radioimmunoassay (CsA RIA kit) method. This drug assay was evaluated for precision, calibration, stability, and accuracy. Within-run precision studies utilizing 25 replicate analyses of the three control preparations (containing CsA in the 60-800 ng/ml range) resulted in coefficients of variation (CV) ranging from 1.0 to 9.1%. The CVs of between-run precision determined by assaying the same control drug levels for five consecutive working days ranged from 3.9 to 4.6%. Calibration curve stability was assessed by examining the drift in control values over a 2-week period. Maximum plasma ranged from 82.6 to 108.2%. Four hundred plasma samples were obtained from 30 heart-transplant patients during the first 6 months of CsA therapy and each sample was analyzed simultaneously by TDx and RIA. Linear regression analysis of the results obtained for each patient (x = RIA, y = FPIA) revealed the following mean values: r = 0.87, (CV = 13.7%), slope = 1.47 (CV = 39.2%). Moreover, the concentration of CsA was determined in 35 patient samples both by TDx and high-performance liquid chromatography (HPLC). FPIA results up to 12 times higher than HPLC results have been noted.
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