Association of a new cationic trypsinogen gene mutation (V39A) with chronic pancreatitis in an Italian family.
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Adult↗
Biomedical subjects
N Cappello
Publications and source records attributed to N Cappello.
The relevance of the CD4+ CD26- subset in the identification of circulating Sézary cells.
BACKGROUND: The lack of specific markers for the phenotyping of circulating neoplastic T cells in Sézary syndrome (SS) patients makes it difficult both to ascertain the presence of clonal cells and to quantify the tumour burden in the peripheral blood. In previous reports we showed that the lack of CD26 (dipeptidyl-aminopeptidase IV) is a characteristic feature of circulating Sézary cells (SC). OBJECTIVES: The purpose of this study was to ascertain, by means of high-resolution two-, three- or four-parameter flow cytometry, the relationship between CD26 expression on peripheral blood lymphocytes and peripheral blood involvement in cutaneous T-cell lymphoma patients and to assess its significance in SS diagnosis. METHODS: The patient population included 52 SS patients, 151 mycosis fungoides (MF) patients at different clinical stages (including 14 with blood involvement, B1-MF), 88 patients with erythrodermic inflammatory skin diseases (EISD) and 72 healthy donors (HD). CD26+ values were available in all cases, whereas CD4+ CD26- level measurement was performed in 23 SS, 141 MF, 71 EISD and 72 HD. RESULTS: CD4+ CD26- percentage values were higher than 30% in all but one B1-MF and higher than 40% in all SS cases, whereas HD, EISD and B0-MF patient values were always lower than 30%. A statistically significant difference was found in both CD26- and CD4+ CD26- percentage and absolute values between SS and HD, EISD and B0-MF patients. The CD26- and CD4+ CD26- percentage values (but not the absolute values) were significantly higher in B1-MF compared with HD, EISD and B0-MF patients (P < 0.001). Moreover, CD26- absolute values and CD4+ CD26- percentage and absolute values were significantly higher in SS than in B1-MF (P < 0.001). A statistically significant direct relationship was found between CD4+ CD26- percentage values and the percentage of circulating SC within the lymphoid population in SS and B1-MF (r = 0.77; P < 0.001). The lack of CD26 was confirmed on phenotypically clonal cells in patients with an expanded circulating TCRvbeta population or a T-cell antigen loss. Sorted CD4+ CD26- cells from both SS patients and HD showed the characteristic cerebriform nuclei of SC. CONCLUSIONS: We feel that a CD4+ CD26- percentage value higher than 30% of peripheral blood lymphocytes could correctly identify the presence of peripheral blood involvement in SS and MF patients.
Adult↗
Nosocomial infections in pediatric cardiac surgery, Italy.
OBJECTIVE: To evaluate the incidence of nosocomial infection (NI) in pediatric patients who received cardiothoracic surgery and to identify possible associated risk factors. DESIGN: Prospective observational study. SETTING: The cardiac surgery and cardiac intensive care units at the Regina Margherita Children's Hospital, Turin, Italy. PATIENTS: All patients who underwent surgery from July 20, 1998, to July 19, 1999, were enrolled, except patients with operative catheterization only. METHODS: Clinical data were collected daily from July 20, 1998, to July 19, 1999. NIs were diagnosed according to US Centers for Disease Control and Prevention criteria. RESULTS: 104 patients were included in the present study, 80 (76.9%) of whom underwent extracorporeal circulation. The NI ratio was 48.1% (50/104); the percentage of patients with NI was 30.8% (32/104): 23.1% developed one infection, 7.7% two or more. The rate of NI was 2.17 per 100 days of hospitalization (50/2,304). The most common pathogen was Pseudomonas aeruginosa. Important risk factors were length of preoperative admission >5 days, total length of admission >10 days, open chest during postoperative phase, and cyanotic heart disease. There was a significant association between sepsis and central venous catheterization for 3 days or more. Rate of sepsis was 19 per 1,000 catheter days (16/852). CONCLUSION: NIs represent a frequent complication for children who undergo heart surgery. Based on our data, we suggest decreasing the preoperative stay as much as possible. The higher NI incidence in patients with an open chest postoperatively suggests that an alternative antibiotic strategy should be considered for these patients.
Adolescent↗
Fungal infections in lung transplantation. Incidence, risk factors and prognostic significance.
BACKGROUND AND AIM OF THE WORK: Fungal infections are frequent following lung transplantation and are associated with high mortality and morbidity. The study aims at 1) reporting our experience with fungal infections after lung transplantation; 2) identifying statistically significant correlations between the occurrence of fungal infections and bacterial infections, cytomegalovirus disease, rejection and steroid therapy; 3) assessing whether the presence of fungal infection has an impact on long-term survival. METHODS: 60 lung transplant recipients were studied with respect to incidence, pattern of presentation and median time to presentation of fungal infection after the transplant. Correlation analysis of the variables of interest was undertaken in 30 patients who had a minimum follow-up of 1 year following transplant. RESULTS: The prevalence of fungal infection was 44%; severe infections occurred in 5 patients (11%). The presence of Candida preoperatively was not associated with an increased risk of fungal infection. In a logistic regression analysis, a significant correlation was found between the occurrence of fungal infection and the following variables: respiratory bacterial infections (p = 0.0003), cytomegalovirus disease (p = 0.00001) and steroid therapy (p = 0.04). No statistically significant difference was found between patients who experienced a fungal infection and those who did not, either in univariate or multivariate survival analysis (p = 0.08). CONCLUSIONS: 1) fungal infections are frequent in lung transplant recipients and may be severe in more than 10% of the cases; 2) the presence of fungi preoperatively is not a contraindication to transplantation: an antifungal prophylaxis is probably indicated in such cases postoperatively; we recommend the use of the less nephrotoxic liposomal Amphotericin B by aerosol route; 3) a statistically significant association exists between fungal infections and both steroid therapy and CMV disease; this suggests that a similar antifungal prophylaxis is indicated in these clinical circumstances; 4) the presence of fungal infection is not an independent prognostic factor of long-term survival.
Adolescent↗
Macrophage-mediated immunostimulation modulates therapeutic efficacy of interleukin-2 based chemoimmunotherapy in advanced metastatic melanoma patients.
The biological mechanisms of chemoimmunotherapy efficacy in vivo have not been fully clarified; furthermore, few data are available to predict its efficacy on the basis of clinical and immunological pretreatment factors. In this paper, pre- and post-treatment serum levels of cytokines (interleukin [IL]-6, IL-10, IL-12 and neopterin) and soluble IL-2 receptors (sIL-2R), as well as circulating levels of T-cell and NK subpopulations, were analysed according to clinical outcome in 66 advanced metastatic melanoma (MM) patients treated with subcutaneous IL-2 in association with interferon-alpha, cisplatin and tamoxifen. Our purpose was to correlate the immune modifications during treatment with the clinical response and to define pretreatment factors with predictive value for clinical outcome. The overall response rate was 35%, with a median overall survival of 11.3 months. During treatment, responding patients showed a common marked increase in IL-12 (mainly released by activated macrophages), sIL-2R and neopterin serum levels, associated with high levels of total lymphocytes and circulating natural killer lymphocytes; progressing patients were characterized by an increase in IL-6 serum levels (directly related to the increase in tumour burden). Multivariate analysis showed that high pretreatment IL-12 levels (P = 0.05) and, to a lesser extent, lactate dehydrogenase levels in the normal range (< or = 450 U/I; P = 0.061) are independent favourable prognostic factors for survival. Our results show that macrophage activation in an immunostimulating way either before or during treatment is associated with a better clinical response and improved survival in advanced MM patients treated with IL-2-based chemoimmunotherapy.
Adult↗
Validation of ICTERUS, a knowledge-based expert system for Jaundice diagnosis.
The study aimed to describe an example of the assessment and validation of knowledge-based clinical expert systems. The paper focuses on ICTERUS, an expert system for jaundice diagnosis. It describes system design, the methodology applied for upgrading and validating the program, and the most important outcomes of the validation procedure. The clinical validation of the system on a very large European database (Euricterus Project) shows that diagnostic conclusions are reliable in about 70% of eligible cases. This figure appears acceptable for a system which provides decision support only on the basis of clinical data, assuming that the final decision is achieved under user responsibility. Expected biases, limitations and inconsistencies in the practical application of the system are discussed.
Analysis of Variance↗
Sorbitol removal by the metastatic liver: a predictor of systemic toxicity of intra-arterial chemotherapy in patients with liver metastases.
BACKGROUND/AIM: Hepatic arteriovenous shunting in the metastatic liver reduces the advantages of intraarterial infusion of chemotherapeutic agents because of the passage of drugs into the systemic circulation. The aim of this study was to quantitatively assess spontaneous functional hepatic arteriovenous shunting in patients with liver metastases and to determine its implication in the increase in systemic toxic effects of intra-arterial infusion chemotherapy with floxuridine. METHODS: Twenty-five patients who underwent implantation of arterial ports for regional chemotherapy of liver metastases were studied. Functional hepatic arterio-venous shunting was evaluated through the bioavailability of intra-arterially administered D-sorbitol, a safe, natural compound whose kinetic features make its hepatic clearance flow dependent. In addition, D-sorbitol hepatic clearance (a parameter reflecting functional liver blood flow) and common liver function tests were evaluated for each studied patient. Patients were then grouped with respect to the percentage of medically-assessed liver occupation by metastases and with respect to systemic toxicity of the chemotherapeutic treatment. Both univariate and multivariate analyses by Student's t-test and stepwise logistic regression, respectively, were performed in both groups for each of the evaluated parameters (age, liver function tests, D-sorbitol hepatic clearance and arterial bioavailability). RESULTS: Arterial bioavailability of D-sorbitol ranged between 0.05 and 0.72 and was significantly greater in patients with more than 50% liver occupation (0.39+/-0.19) compared with those with minor liver involvement (0.17+/-0.13; p = 0.003); it was also significantly greater in patients experiencing high-grade systemic toxicity (0.40+/-0.19) compared with those with low-grade toxicity (0.16+/-0.11; p<0.001). Multivariate analysis showed that arterial bioavailability of D-sorbitol was the only parameter among those evaluated which was able to predict systemic toxicity of this kind of chemotherapy. CONCLUSIONS: Our results show that, in the metastatic liver, arterial bioavailability of D-sorbitol, an index of functional arteriovenous shunting, varies widely, is significantly greater in patients with massive liver occupation and it is a good predictor of systemic toxicity of intra-arterial regional chemotherapy with floxuridine.
Adult↗
Evaluation of hepatic function in liver cirrhosis: clinical utility of galactose elimination capacity, hepatic clearance of D-sorbitol, and laboratory investigations.
Assessment of hepatic function is based on both liver blood tests and functional tests, the extensive application of which is still controversial. The aim of this study was to evaluate the clinical utility of a few selected tests as discriminatory and prognostic indexes: serum albumin, pseudocholinesterase, prothrombin time, as well as galactose elimination capacity and hepatic sorbitol clearance. Two separate studies were performed: Study I to investigate how well these tests assessed severity, and Study II to evaluate their prognostic value. A total of 128 consecutive cirrhotic patients classified according to the Child-Pugh score were included in Study I; Study II was carried out on 47 of these 128 during a two-year follow-up period. Pairwise correlations between all tests and Child-Pugh score yielded higher significant values for liver blood tests than for the functional ones. In Study I functional tests such as galactose elimination capacity and hepatic sorbitol clearance did not appear to be better than conventional biochemical tests in discriminating clinical severity of cirrhotic patients, as defined by Child-Pugh classification. Results of Study II confirmed that in severe liver cirrhosis Child-Pugh score remains the best method for medium- and long-term prognosis and for planning liver transplantation. Functional tests should be reserved for defining the residual functioning liver mass or for studies about functional liver plasma flow.
Adolescent↗
Prognostic factors in Sézary syndrome: a multivariate analysis of clinical, haematological and immunological features.
BACKGROUND: Sézary syndrome (SS) prognostic factors are not well defined because of the rarity of this disease. The specific goal of this prospective study was to assess by multivariate analysis the predictive value with respect to survival of a series of clinical, haematological and immunological parameters taken at SS diagnosis. PATIENTS AND METHODS: A cohort of 62 SS patients diagnosed and followed since 1975 was examined, and 51 were included in the multivariate analysis model. RESULTS: The median survival time was 31 months (range: 1 month-15.7+ years), and the five-year survival rate 33.5%. The following variables were found by univariate analysis to be associated with a poor prognosis at the time of SS diagnosis: previous history of mycosis fungoides (P = 0.013), high number of circulating leukocytes (P = 0.001), Sézary cells (SC) (P < 0.001) and CD4+ cells (P < 0.001), presence of large circulating SC (P < 0.001), above normal range LDH serum levels (P = 0.015), presence of PAS-positive inclusions in the cytoplasm of circulating SC (P < 0.001), high CD4/CD8 ratio (P = 0.004) and a CD7 negative circulating SC phenotype (P < 0.001). Among them, the stepwise multivariate analysis selected as adverse independent prognostic factors: PAS-positive cytoplasmic inclusions (P = 0.001), CD7 negative phenotype (P = 0.018) and presence of large circulating SC (P = 0.045). CONCLUSIONS: Two low-/high-risk groups have been singled out on the basis of the risk index. Patients with no or one adverse prognostic feature(s) (risk index < or = 1; n = 31) share a slow disease course and a relatively favorable prognosis (five-year survival: 58%); on the other hand, patients with 2 or 3 adverse prognostic feature (risk index > 1; n = 20) are characterized by an aggressive disease course not modifiable by traditional therapies (five-year survival: 5%).
Adult↗
Recurrence of thymoma: analysis of clinicopathologic features, treatment, and outcome.
OBJECTIVE AND METHODS: This study reports clinicopathologic features, treatment, and outcome of 30 recurrent thymomas out of 266 totally resected thymomas. RESULTS: The mean disease-free interval to recurrence was 86 months. Recurrence occurred less frequently and after a longer disease-free interval after resection of encapsulated versus invasive thymomas. The presence of associated myasthenia gravis did not affect recurrence proportion, disease-free interval, or survival after recurrence. A local recurrence occurred in 11 patients, 17 patients had a distant recurrence, and the extent of the recurrence could not be determined in 2 cases. Surgical treatment of the recurrent tumor was attempted in 16 cases, and a total resection was possible in 10 cases; exclusive radiotherapy was done in 11 cases. Overall 5- and 10-year survivals were 48% and 24%, respectively. In a univariate analysis, survival was significantly better in the presence of a local recurrence and in case of a total resection of the recurrent tumor. The use of adjuvant therapy after the resection of the initial thymoma had no effect on reducing the incidence of recurrence, in prolonging the disease-free interval, or in improving survival after the development of the recurrence. In a multivariate survival analysis, significant prognostic factors were the presence of a local recurrence and total resection of the recurrent tumor. CONCLUSIONS: Surgical resection is recommended in patients with recurrent thymoma. Local recurrence and total resection of the recurrent tumor are associated with excellent prognosis. A poor prognosis may be anticipated in the presence of distant recurrence and when radical surgical treatment is not done.
Adult↗
Genetic history of cystic fibrosis mutations in Italy. I. Regional distribution.
Earlier analysis of the Italian population showed patterns of genetic differentiation that were interpreted as being the result of population settlements going back to pre-Roman times. DNA disease mutations may be a powerful tool in further testing this hypothesis since the analysis of diseased individuals can detect variants too rare to be resolved in normal individuals. We present data on the relative frequencies of 60 cystic fibrosis (CF) mutations in Italy and the geographical distribution of the 12 most frequent CF mutations screened in 3492 CF chromosomes originating in 13 Italian regions. The 12 most frequent mutations characterize about 73% of the Italian CF chromosomes. The most common mutation, delta F508, has an average frequency of 51%, followed by N1303K and G542X, both with average frequencies around 5%. Multivariate analyses show that the relative frequencies of CF mutations are heterogeneous among Italian regions, and that this heterogeneity is weakly correlated with the geographical pattern of non-DNA 'classical' genetic markers. The northern regions are well differentiated from the central-southern regions and within the former group the western and eastern regions are remarkably distinct. Moreover, Sardinia shows the presence of mutation T338I, which seems absent in any other European CF chromosome. The north-western regions of Italy, characterized by the mutation 1717-1G-->A, were under Celtic influence, while the north-east regions, characterized by the mutations R1162X, 2183AA-->G and 711 + 5G-->A, were under the influence of the Venetic culture.
Cystic Fibrosis↗
Monoethyl glycine xylidide (MEGX) test evaluation in primary biliary cirrhosis: comparison with Mayo score.
OBJECTIVE: To evaluate the clinical and prognostic value of the monoethyl glycine xylidide (MEGX) test in patients with primary biliary cirrhosis (PBC) in comparison with the Mayo score (Mayo). DESIGN: A prospective study. METHODS: MEGX determinations at enrolment were compared to the Mayo score as well as to conventional clinical and laboratory parameters in 92 patients with PBC. RESULTS: The MEGX test yielded higher basal values in long-term survivors compared to patients that were transplanted or died during the follow up; patients belonging to the last two groups displayed significantly higher Mayo scores at baseline. Although values for prothrombin time, serum albumin, alkaline phosphatase, cholesterol, cholinesterase, and gamma-glutamyltranspeptidase were significantly different in survivors compared to either transplanted or dead patients at univariate analysis, the multivariate analysis demonstrated an independent prognostic value for the MEGX and the Mayo score solely. The best discrimination between probability of death or survival was achieved with a cutoff value of 25 ng/ml for the MEGX test and of 6 for the Mayo score. When plotting both MEGX test and Mayo score, the point distribution displayed a bimodal trend, and the wide range of values given by the MEGX test was observed to supply a more precise assessment of liver reservoir and a better discrimination of progressive changes in liver function; the limited range of the Mayo score for values below 6 could only identify gross deteriorations. CONCLUSION: Our data show that the asymptomatic progressive functional deterioration occurring during the natural history of PBC can be monitored by the MEGX test because it appears to be able to identify abnormalities prior to the onset of alterations in conventional laboratory and/or clinical parameters which are likely to affect the Mayo score.
Adult↗
Mode of delivery and gestational age influence perinatal HIV-1 transmission. Italian Register for HIV Infection in Children.
Some data suggest that cesarean section reduces mother-to-child HIV-1 transmission. To assess the influence of mode of delivery and other maternal and infant factors on the rate of transmission, we analyzed the data of 1,624 children prospectively followed from birth. Of these, at the last visit 1,033 were > 18 months of age or would have been had they not died of HIV-related illness. Among the 975 first singleton children, 180 [18.5%; 95% confidence limits (CL), 16.1-20.9] acquired infection, as did 8 of 56 (14.3%; 95% CL, 5.1-23.5) second-born children. Multivariate stepwise analysis showed that vaginal delivery and development of symptoms in the mother were significantly and independently associated with a higher transmission rate (vaginal delivery; odds ratio, 1.69; 95% CL, 1.14-2.5; symptoms: odds ratio, 1.61; 95% CL, 1.12-2.3). In contrast, a history of maternal drug use, birth weight, breast-feeding (only 37 infants were breast-fed), and child's sex did not have a significant impact on viral transmission. The percentage of infected children was highest (30.7%) among very premature infants (< or = 32 weeks of gestation); this significant trend subsequently decreased to 11.9% at the week 42 (p < 0.001), suggesting a parallel reduction in peripartum transmission. The reduced rate of infection observed in infants born by cesarean section underlines the urgent need for randomized controlled trials to evaluate the protective role of surgical delivery in preventing perinatal HIV-1 transmission.
Birth Weight↗
Genetic analysis of Sardinia: I. data on 12 polymorphisms in 21 linguistic domains.
(1) The microgeographic structure of Sardinia, well documented from a historical and linguistic point of view, further supported by archaeological evidence, can also be dissected at the genetic level: gene frequencies show heterogeneities which are statistically significant. (2) Dendrogram analyses performed with different methods lead to the same result: even if gene frequencies cluster linguistically defined geographic domains in agreement with historical and archaeological evidence, no phylogenetic tree can be inferred, very likely because the assumptions which allow a phylogenetic tree to be a valid model of evolution (mainly constant evolutionary rates and independence between branches) do not apply to the genetic history of Sardinia. (3) Evidence of a qualitative association between distribution of genes and distribution of languages or dialects seems to emerge also at the microgeographic level of our analysis. More linguistic and genetic data are planned to be considered.
Female↗
Computer-aided diagnosis in jaundice: comparison of knowledge-based and probabilistic approaches.
The study reported in this paper is aimed at evaluating the effectiveness of a knowledge-based expert system (ICTERUS) in diagnosing jaundiced patients, compared with a statistical system based on probabilistic concepts (TRIAL). The performances of both systems have been evaluated using the same set of data in the same number of patients. Both systems are spin-off products of the European project Euricterus, an EC-COMAC-BME Project designed to document the occurrence and diagnostic value of clinical findings in the clinical presentation of jaundice in Europe, and have been developed as decision-making tools for the identification of the cause of jaundice based only on clinical information and routine investigations. Two groups of jaundiced patients were studied, including 500 (retrospective sample) and 100 (prospective sample) subjects, respectively. All patients were independently submitted to both decision-support tools. The input of both systems was the data set agreed within the Euricterus Project. The performances of both systems were evaluated with respect to the reference diagnoses provided by experts on the basis of the full clinical documentation. Results indicate that both systems are clinically reliable, although the diagnostic prediction provided by the knowledge-based approach is slightly better.
Artificial Intelligence↗
Analysis of HLA-A, C, B, DR and DQ loci in an Italian sample of possible Celtic origin.
Trino Vercellese, a village of Piedmont (Italy), was selected with the aim at reconstructing the genetic history of a putative Celtic sample known to be settled in Italy with the name of Rigomagus since pre-roman times. The HLA-A, Cw, B, DR and DQ antigens of 101 unrelated individuals have been typed. The antigens characterizing this sample for their higher frequency are shown to be A3, A11, A32, B35, B39, Bw52, Cw4, DRw11, DRw13, DQw7. Gene frequencies are estimated by maximum likelihood and Hardy-Weinberg equilibrium was tested with no deviant genetic locus. Two-locus haplotype frequencies were also estimated and those with significant associations tabulated. "Extended" haplotypes were reconstructed: the three most frequent haplotypes (covering a total frequency of 11.5%) share the same Cw, B, DR and DQ alleles. Comparisons with other Italian and European samples are indicated to challenge archeological evidence of a pre-roman genetic stratification of the people living in our old Rigomagus.
Alleles↗
HLA supratypes in an Italian population.
A supratype analysis of a North Italian population was performed, using 16 polymorphisms in the HLA region spanning the HLA-A-DP segment. Fourteen supratypes were identified, mostly corresponding to those found in other Caucasoid populations. The degree of their conservation both within the B-DR/DQ region and in the regions telomeric and centromeric from HLA-A and DP was evaluated and linkage disequilibria among several DR and DP alleles were identified. Notably, the degree of association with DP increased when the DR marker was part of a conserved B-DR/DQ supratype. These data are relevant to the definition of the genetic structure of the population and to the prediction of probabilities of histocompatibility matching between unrelated individuals.
HLA Antigens↗
Frequencies of HLA class II alleles in Piedmont (northern Italy).
HLA class II gene frequencies were analysed in a panel of 101 unrelated individuals with Piedmontese ancestors living in Piedmont (north western Italy). A class II genomic typing was performed using the XI Histocompatibility Workshop protocol based on locus specific amplification by Polymerase chain Reaction (PCR) of class II gene second exon and hybridization with sequence specific oligonucleotides (SSO). Compared to other HLA typing techniques, this protocol defines more class II subtypes and analyses HLA-DP gene polymorphisms. The frequencies of alleles at DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, DPB1 loci are reported. Linkage disequilibrium analysis between DPA1-DPB1 and DRB1-DPB1 alleles is also reported.
Alleles↗