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Biomedical subjects

S Calabrese

Publications and source records attributed to S Calabrese.

At least 19 recordsLinked to original sources

Addition of sirolimus to cyclosporine in long-term kidney transplant recipients to withdraw steroid.

The aim of this study was to evaluate the feasibility of a steroid-free maintenance immunosuppression regimen in long-term renal transplant (KTx) recipients after addition of sirolimus (SRL) to cyclosporine (CsA)-based immunosuppression. A multicenter, prospective pilot study of steroid withdrawal (SW) was initiated for KTx patients. SW was divided into three phases: (A) conversion to a SRL + CsA + steroid regimen; (B) steroid tapering and withdrawal; and (C) maintenance with SRL + CsA. Primary endpoints of the study were incidence of acute biopsy-proven rejection (AR) and safety. In the A and B phases of the study 42 KTx patients (132 +/- 75 months post-Tx) were entered into the study, 18 of 42 (43%) with severe, acute side effects due to the CsA + SRL combination. These side effects were reversible with reduction of CsA or with suspension of the SRL/CsA combination. An amendment was introduced in the protocol to drastically reduce the CsA exposure to <50 ng/mL (trough) at the time of SRL addition. After this amendment, 39 other KTx patients entered the study and only 3 of 39 (8%) were discontinued because of toxic side effects. In the overall cohort of 81 KTx patients, the incidence of AR after SW was low (n = 5, 6.1%), all occurring within the first 3 months after SW. These findings indicate: (1) addition of SRL to very low-maintenance CyA exposure allows safe SW in KTx; (2) with the SRL + CsA combination, the incidence of AR after SW is low in long-term KTx patients; and (3) in the first 3 months after SW strict monitoring for early diagnosis and treatment of AR is mandatory.

Adrenal Cortex Hormones↗

Use of sequence information in associative learning in control subjects and cerebellar patients.

Previous studies of our group have shown that cerebellar patients are impaired in their ability to associate a color and a numeral or two colors with a button push. The aim of the present study was to examine whether control subjects make use of sequence information in visuomotor associative learning tasks and if this ability is impaired in cerebellar patients. A group of eight patients with degenerative cerebellar disease and eight age, sex and IQ matched controls were tested. Subjects had to learn the association between pairs of colored squares and a button push. Two colored squares were shown one after the other in a fixed or random order on a computer screen. Control subjects but not cerebellar patients took advantage of the fixed order information of colored squares in order to improve associative learning. Differences between groups could not be explained by differences in verbal and visuospatial short-term memory, color discrimination, affective state or motor disturbances. Results suggest that impaired sequencing of sensory stimuli may contribute to disorders in visuomotor associative learning in cerebellar patients.

Adult↗

Design of a trial comparing sirolimus plus mycophenolate mofetil versus sirolimus plus cyclosporine.

We present the study design of a prospective, multicenter, randomized trial aimed at comparing the effects of two different combinations of sirolimus. Renal transplant recipients will be allocated to receive either sirolimus and mycophenolate mofetil (group A) or sirolimus and cyclosporine (group B). The primary endpoint will be the graft function at 3, 6, 12, 24, 36, 48, and 60 months. A number of secondary endpoints will also be considered. To obtain a significant difference in the primary endpoint 180 patients will be enrolled.

Adult↗

Atherosclerosis and inflammation. Patterns of cytokine regulation in patients with peripheral arterial disease.

Inflammatory phenomena at sites of atherosclerotic plaques are increasingly thought to be major determinants of the progression and clinical outcome of atherosclerotic disease. Therefore, attention is being paid to systemic markers/mediators which may reflect the inflammatory activity in the plaques. This study evaluates the pattern of the main proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), their soluble receptors/antagonist, and a variety of inflammatory markers, in patients with peripheral arterial disease (PAD). Eight patients with PAD suffering from claudicatio intermittens (CI), eight with critical limb ischemia (CLI) and eight controls (C) were studied. Blood samples were collected at baseline in all groups and. for C and CI, immediately after and 4 h after a 30-min treadmill test. Baseline: no differences in cytokine plasma levels were detected among the three groups. In contrast, soluble receptors of TNF (type I and II) and of IL-6, and IL-1beta receptor antagonist (IL-1ra) were increased in CI and CLI patients, as compared to C. Of note, IL-Ira correlated with the occurrence and stage of the disease in a highly significant proportion of the patients, reaching a predictive value for the disease of P < 0.0001. The opposite trend was observed for the soluble receptor of IL-1beta. Notably, in the patients no alterations could be found in white blood cell counts, expression of CD11c adherence molecule by circulating monocytes or, in vitro. O2- release from zymosan-activated neutrophils. Moreover, plasma levels of platelet activating factor (PAF), of neutrophil elastase and of the acute phase reactants C-reactive protein (CRP) and alpha1-acid glycoprotein were not found to be significantly altered. In contrast, the acute-phase proteins alpha1-antitrypsin (alpha1AT) and haptoglobin (HG) were found to be increased. Effect of treadmill: IL-1beta and TNFalpha remained at baseline levels following exercise, and IL-6 dropped to undetectable levels. Among cytokine antagonists, again the most relevant changes concerned the IL-1ra, which was significantly increased immediately after the treadmill test, both in CI and C, and returned to baseline levels after 4 h. In contrast, soluble TNFalpha, IL-1beta and IL-6 receptors, PAF, and the other markers of leukocyte activation were not found to be altered. Soluble TNFalpha and IL-6 receptors were shown to inhibit the biological effects of their ligands. Similarly, IL-1ra and the acute phase proteins alpha1AT and HG have been reported to exert anti-inflammatory functions. The increased plasma levels of these agents, together with low levels of inflammatory cytokines and other pro-inflammatory mediators such as PAF and alpha1-acid glycoprotein, appear to draw an undescribed picture, so far, of upregulation of a composite systemic anti-inflammatory mechanism in atherosclerotic patients. IL-1ra appears to be a reliable marker of the state of activation of this mechanism. These results may provide a basis for developing new insights into the pathogenesis of the atherosclerotic disease.

Acute-Phase Proteins↗

D-dimer and anticoagulation in patients with mechanical prosthetic heart valves. A 2-year follow-up.

The best anticoagulation level in patients with mechanical heart valve prostheses is still being debated. D-dimer, which detects the presence of cross-linked fibrin degradation products, has been demonstrated to be a useful marker of coagulation activation. This study was designed to verify whether heart valve prostheses in anticoagulated patients are associated with abnormalities in D-dimer plasma levels, and if so, whether such levels are related to the anticoagulation level and/or whether they could be predictive of acute vascular or hemorrhagic events. In 132 patients with single and 10 with double mechanical valve replacement, international normalized ratio (INR) and D-dimer plasma levels were determined. The INR levels of the previous 8 months were reviewed to assess the time that each patient spent in the therapeutic range. The D-dimer plasma levels were compared with those obtained from 102 matched control subjects. The patients were then followed up for 2 years to record acute vascular and hemorrhagic events. For the entire group, D-dimer plasma levels in patients were the same as those in the control group. Patients with double valve replacement had higher D-dimer plasma levels than either monovalvular implant patients or control subjects. Patients who had spent < 75% of the time within the assigned anticoagulation range had higher values for D-dimer plasma levels (median, 270 vs 198 ng/mL, P = .02). The major determinants of D-dimer plasma levels were age (R2 = .07, P = .009) and the percentage of time spent below the predetermined INR level (R2 = .09, P = .001). During follow-up, 19 acute vascular and 16 hemorrhagic events occurred. High D-dimer tertile was the only parameter predicting the occurrence of thromboembolic events. In patients with mechanical heart valve prostheses, the D-dimer plasma level depended on the thoroughness of anticoagulation. Patients in the upper tertile of D-dimer values have an approximately 5-fold risk of vascular thromboembolic events. D-dimer determination can therefore be useful in detecting patients who are at a higher risk of severe vascular events.

Adult↗

[Detection of cognitive deterioration in elderly patients attending an emergency hospital service].

BACKGROUND: An increasing proportion of patients attended at hospital emergence departments (HED) are elderly people. OBJECTIVES: a) To check the reliability of the usual medical assessment to detect the cognitive deterioration in elderly people attended at HED, compared with that performed systematically by means of an evaluation test of cognitive functions; b) to study the applicability of such a test in HED, on the basis of the time necessary for its administration, and c) to describe the deterioration prevalence in that group of patients and identify the possible associated risks for its detection in patients. PATIENTS AND METHODS: Prospective study including patients aged > or = 60 years attended at a HED, using the orientation, memory and concentration test (OMC) to perform the cognitive assessment. RESULTS: A total of 352 patients who had no exclusion criteria out of the 536 attended during the study period were included. Cognitive deterioration was not detected in 111 patients (31.5%); it was mild in 147 (41.8%), moderate in 71 (20.2%) and severe in 23 (6.5%). In patients with moderate-severe deterioration according to the OMC test, such a deterioration was detected by the usual medical evaluation in 7% of cases. The mean time in completing the test was 2.6 +/- 0.9 minutes. An age > or = 80 years was associated with an increased relative risk for detecting moderate-severe cognitive deterioration (1.98; 95% CI, 1.42-2.78; p < 0.001), whereas the discharge diagnosis of respiratory disease was associated with a decrease of the relative risk (0.41; 95% CI, 0.19-0.89; p < 0.05). No association was observed with other factors, such as gender, home residence or final destination from the emergency department. CONCLUSIONS: The prevalence of cognitive deterioration in elderly people attended at HED is high and increases with age. The OMC test can be administered at HED to detect cognitive deterioration, which is not frequently detected by the usual medical assessment.

Age Factors↗

Activation of coagulation by a LDL-apheresis device.

LDL-apheresis often induces an almost constant and progressive increase of the differential pressure of plasma flowing through the dextran sulphate cellulose column, reducing the efficacy of the treatment. On two occasions we were able to identify a fibrin plug by immunofluorescence. Our aim was to verify the modification of some coagulation indicators in patients undergoing LDL-apheresis and whether an activation of coagulation occurs in the LDL-apheresis device. Blood samples were obtained from six patients with familial hypercholesterolaemia who were undergoing LDL-apheresis. During the same session further blood/ plasma samples were taken from the LDL-apheresis device at different sites and at different volumes of filtered blood. In patients after LDL-apheresis the following modifications were found: a 25% decrease of fibrinogen and a slight increase in F1 + 2 plasma levels. No relevant changes in thrombin-antithrombin complexes and fibrinopeptide A plasma levels were noted. In the LDL-apheresis device the main results were: (a) fibrinogen was trapped in the dextran sulphate cellulose column in the early phases; (b) activation of coagulation was recognisable in the plasma separator during the procedure and progressively increased with duration of LDL-apheresis; (c) thrombin-antithrombin complexes, formed in the plasma separator, were retained by the dextran sulphate cellulose column. In conclusion, LDL-apheresis activates coagulation in the device. Shortening cycle time or using nafamostat mesilate as an anticoagulant, could be interesting alternatives for improving the procedure.

Aged↗

[Utilization of antibiotics in a hospital emergency department. Quality of prescription].

OBJECTIVES: To know the frequency of antibiotic prescription, the conditions that motivate their usage, and to evaluate the quality of such therapies in a hospital emergency department (HED). METHODS: Retrospective study of 2,677 patients attended at a HED for a one-month period including those who had antibiotics prescribed in the discharge report. The parameters used to evaluate the therapeutic quality included the condition amenable to antibiotic therapy, appropriate antibiotic, dosage, interval of administration, and duration. Each parameter had a score which was used to quantitate the quality in a 0 to 100 scale. RESULTS: A total of 288 patients (10.7%) had antibiotics prescribed for treatment of respiratory tract infections (53.8%) and urinary tract infections (19.4%). The antibiotic group that accounted for most prescriptions was broad-spectrum penicillins (45%), followed by quinolones (12.8%), and urinary antiseptics (11.4%). Only 100 (50.3%) treatments were considered correct for all parameters analyzed. The most inadequate parameters were: non-appropriate antibiotic in 17.1% of cases and incorrect length of administration in 39.9%. The average quality according to scale was 89.6 (SD = 20.3). A lower quality was observed for treatments prescribed when on duty compared with normal working time (p = 0.006). CONCLUSIONS: Antibiotics are drugs frequently prescribed in HED. Errors were detected in choosing antibiotic therapies and antibiotic course duration in our department, which makes the adoption of intervention measures for its correction necessary.

Drug Prescriptions↗

[Effects of cyclosporin A on various indices of cholestasis in kidney transplant recipients].

A cholestatic syndrome has been reported as one of the main side effects of CyA therapy. The aim of the present study was to evaluate frequency and degree of severity of the cholestatic syndrome in a group of patients with renal transplant treated with CyA. In 55 patients we evaluated both clinical: jaundice, pruritus, presence of biliary lithiasis and biochemical parameters: total serum biliary salts (TBS), total bilirubin (TB), alkaline phosphatase (AP), gammaglutamyl transpeptidase (GGT), transaminase (AST, ALT), cholesterol (CT), triglycerides (TG), HDL-cholesterol (HDL-C) and compared them with a control group matched for sex and age. In the transplant patients significantly higher values of TBS, TB, AP (p < 0.05) were found; 55% of the patients had above mean values of at least one of the classical parameters of liver function and an higher frequency of biliary lithiasis was also found, in the absence of the classical risk factors. However, none of the patients presented severe signs of hepatic disease and to date it has never been necessary to stop treatment. In conclusion, our study shows that the dosage of CyA used at present is quite safe; however, it is necessary to monitor in these patients some parameters of liver function to prevent the minor side effects we observed from progressing into more serious damage.

Adult↗

[Disseminated candidiasis in parenteral drug addicts. Report of 15 cases].

Fungic infections related to parenteral use of drugs increased significantly from 1980 on with the description of the disseminated candidiasis syndrome. Associated to the administration of brown heroin, this syndrome is characterized by the development of cutaneous, ocular and osteoarticular infections, isolated or combined, by Candidas albicans. We present 15 patients with disseminated candidiasis: 12 developed ocular affection (10 endophthalmitis and 2 chorioretinitis): 9, cutaneous lesions and 3 osteoarticular affection (3 costochondritis and one hip arthritis); 8 presented simultaneous infections in several locations. The biopsy and culture of the cutaneous lesions was the most profitable test in order to establish the microbiological diagnosis. We comment on the main etiopathogenetic, clinical, diagnostic and therapeutic aspects of the disseminated candidiasis syndrome.

Adolescent↗

Fibrinogen, D-dimer and thrombin-antithrombin complexes in a random population sample: relationships with other cardiovascular risk factors.

Fibrinogen is an independent risk factor for cardiovascular disease and both D-Dimer and Thrombin-Antithrombin complexes may be suitable as laboratory markers of deep venous thrombosis and are becoming more widespread in clinical practice. The aim of our study was to evaluate their normal range and to examine their correlation with various cardiovascular risk factors. Fibrinogen, D-Dimer and Thrombin-Antithrombin complexes were assessed in 516 normal subjects randomly selected from the National Health Service register of Trieste (Italy). In our community the mean value of fibrinogen was 283 +/- 71 mg/dl. Fibrinogen increases with age in males and was significantly higher in male smokers. In non-smokers, females had significantly higher fibrinogen values than males. The mean value of D-Dimer was 306 +/- 130 ng/ml. In females it is significantly higher. The fibrinogen and D-Dimer correlation coefficient was 0.20 (p < 0.001). The mean level of Thrombin-Antithrombin complexes was 6.25 +/- 6.8 ng/ml with a distribution markedly skewed towards the left; males had lower concentration than females (p = 0.047). Multiple regression analysis for fibrinogen as a dependent variable showed that D-Dimer, LDL-cholesterol, Body-Mass Index and Thrombin-Antithrombin complexes were poor predictors for fibrinogen plasma levels (R2 = 0.23) and that fibrinogen, ApoA1 and age can explain only about 10% of the observed variability in D-Dimer.

Adult↗

Sternoclavicular joint infection due to Bacteroides oralis.

A 60-year-old man in good health with no history of intravenous drug abuse was hospitalized for sternoclavicular joint pain and swelling. His complicated course required extensive debridement of the sternoclavicular joint. An insidious course, negative blood culture and requirement for surgery is common in infections of this joint.

Abscess↗

Restraint-review committee: a working model.

Initially, the goal of this committee was to reduce the number of unnecessary physical restraints (see Table 4). This was achieved by a team approach and a systematic process of assessment, monitoring, and evaluation. In addition, this process provided a means by which restraint use could be thoroughly documented and functionally monitored. Efforts are continuing in order to provide a safe environment while at the same time promoting quality of life through reduction of restraints.

Aged↗

Compartmental syndrome due to viper bite.

The case is reported of a young girl who was bitten on the hand by a viper and developed compartment syndrome of the intrinsic muscles more than 24 h later. Multiple dorsal and volar fasciotomies resolved the acute episode with complete restitutio ad integrum. The clinical case is discussed in detail and the literature on these rare complications of snake bites in European countries reviewed.

Acute Disease↗